PMID- 22665573 TI - UNG shapes the specificity of AID-induced somatic hypermutation. AB - Secondary diversification of antibodies through somatic hypermutation (SHM) and class switch recombination (CSR) is a critical component of the immune response. Activation-induced deaminase (AID) initiates both processes by deaminating cytosine residues in immunoglobulin genes. The resulting U:G mismatch can be processed by alternative pathways to give rise to a mutation (SHM) or a DNA double-strand break (CSR). Central to this processing is the activity of uracil-N glycosylase (UNG), an enzyme normally involved in error-free base excision repair. We used next generation sequencing to analyze the contribution of UNG to the resolution of AID-induced lesions. Loss- and gain-of-function experiments showed that UNG activity can promote both error-prone and high fidelity repair of U:G lesions. Unexpectedly, the balance between these alternative outcomes was influenced by the sequence context of the deaminated cytosine, with individual hotspots exhibiting higher susceptibility to UNG-triggered error-free or error prone resolution. These results reveal UNG as a new molecular layer that shapes the specificity of AID-induced mutations and may provide new insights into the role of AID in cancer development. PMID- 22665574 TI - Runx1-Cbfbeta facilitates early B lymphocyte development by regulating expression of Ebf1. AB - Although Runx and Cbfbeta transcription factor complexes are involved in the development of multiple hematopoietic lineages, their precise roles in early mouse B lymphocyte differentiation remain elusive. In this study, we examined mouse strains in which Runx1, Runx3, or Cbfbeta were deleted in early B lineage progenitors by an mb1-cre transgene. Loss of Runx1, but not Runx3, caused a developmental block during early B lymphopoiesis, resulting in the lack of IgM(+) B cells and reduced V(H) to DJ(H) recombination. Expression of core transcription factors regulating early B cell development, such as E2A, Ebf1, and Pax5, was reduced in B cell precursors lacking Runx1. We detected binding of Runx1-Cbfbeta complexes to the Ebf1 proximal promoter, and these Runx-binding motifs were essential to drive reporter gene expression. Runx1-deficient pro-B cells harbored excessive amounts of the repressive histone mark H3K27 trimethylation in the Ebf1 proximal promoter. Interestingly, retroviral transduction of Ebf1, but not Pax5, into Runx1-deficient progenitors restored not only development of B220(+) cells that underwent V(H) to DJ(H) rearrangement but also expression of B lineage signature genes. Collectively, these results demonstrate that Runx1-Cbfbeta complexes are essential to facilitate B lineage specification, in part via epigenetic activation of the Ebf1 gene. PMID- 22665575 TI - Oophorectomy and breast cancer in BRCA mutation carriers--letter. PMID- 22665576 TI - Age-specific effectiveness of the Finnish cervical cancer screening programme. AB - BACKGROUND: There is currently some uncertainty about the effectiveness of screening outside the established core ages of 30 to 60. We audited the screening histories of cervical cancers and conducted a case-control evaluation of the effectiveness of organized screening in different ages. METHODS: Screening histories for 1,546 cervical cancer cases and 9,276 age-matched controls were derived by linkage to the screening register. ORs and 95% confidence intervals (CI) for the association of participation in a program screen and cervical cancer diagnosis in the following screening interval were estimated using conditional logistic regression and corrected for self-selection bias. RESULTS: Participation in a single screen was associated with a 47% decrease in cervical cancers, but this effect was age-dependent. Screening at 25 showed little or no impact on the risk of cervical cancer in the next interval, whereas screens at 40 to 65 showed protective effects of 51% to 66%. CONCLUSIONS: Program screening at the age of 25 is not associated with a reduced risk of cervical cancer in the following screening interval. Additional analyses are needed that also take opportunistic screening of women during the first rounds of organized screening into consideration. In contrast, screening yields substantial risk reductions in older ages at least up to the age of 60. This study also provides moderate indication of a long-lasting risk reduction associated with screening at the age of 65. IMPACT: Cervical cancer screening effectiveness is for the first time evaluated at different ages up to 65 with correction for self-selection bias of participation in organized screening. PMID- 22665577 TI - Overexpression of protein phosphatase 4 correlates with poor prognosis in patients with stage II pancreatic ductal adenocarcinoma. AB - PURPOSE: Protein phosphatase 4 (PP4) has been reported to be overexpressed in breast and lung cancers. PP4 plays an important role in the regulation of centrosome maturation, DNA repair, NF-kappaB, and c-jun-NH(2)-kinase (JNK) signaling pathways. However, the expression and functions of PP4 in pancreatic cancer have not been studied. EXPERIMENTAL DESIGN: We examined the expression of PP4 catalytic subunit (PP4C) protein in 133 patients with stage II pancreatic ductal adenocarcinoma (PDAC) and their paired benign pancreatic samples (N = 113) by immunohistochemistry. To confirm the immunohistochemical results, we measured PP4C protein and mRNA levels by Western blotting and real-time reverse transcriptase PCR. Using univariate and multivariate analysis, we correlated PP4C expression with survival and other clinicopathologic features. RESULTS: PP4C was overexpressed in 75 of 133 (56.4%) stage II PDAC samples, which was significantly higher than the paired benign pancreatic tissue (15%, 17 of 113). PP4C mRNA expression levels were also higher in PDAC samples than the paired benign pancreatic tissue. Overexpression of PP4C in PDAC samples was associated with higher frequencies of distant metastasis (P = 0.02) and poor disease-free and overall survivals in patients with stage II PDAC (P = 0.006 and 0.02) independent of tumor size, margin status, and lymph node status (stage). CONCLUSIONS: Our study showed that PP4C is overexpressed in PDAC. Overexpression of PP4C in PDAC samples is associated with poor prognosis in patients with stage II PDAC. Therefore, targeting PP4 signaling pathway may represent a new approach for the treatment of PDAC. IMPACT: Our study showed that PP4C is an independent prognostic factor in patients with stage II PDAC. PMID- 22665578 TI - Genomic methylation changes over time in peripheral blood mononuclear cell DNA: differences by assay type and baseline values. AB - BACKGROUND: Lower levels of genomic DNA methylation in blood DNA has been associated with risk of different cancers and several cancer risk factors. To understand the use of genomic methylation measures as biomarkers of cancer risk, data are needed on within-individual changes over time. METHODS: Using information from 77 subjects with blood collected at 2 visits on average 8 years apart, we examined whether levels of DNA methylation change with time and if so, whether selected cancer risk factors predict these changes. We measured DNA methylation levels in peripheral blood mononuclear cells (PBMC) using three assays that have been used in epidemiologic studies: (i) luminometric methylation assay (LUMA)(ii) LINE-1 by pyrosequencing, and (iii) Sat2 by MethyLight. RESULTS: Close to a third of all individuals had large changes over time (>=10%) in LUMA with 19.5% increasing and 13.0% decreasing. For Sat2, two-thirds of individuals had large changes with 40% increasing and 26% decreasing over time. In contrast, only 3.9% of individuals had large changes in LINE-1 over time. The degree of change in PBMC DNA methylation was statistically significantly inversely associated with methylation levels at baseline; greater decreases were observed in individuals with higher baseline values for each assay. CONCLUSIONS: These data, if replicated, suggest that changes in DNA methylation over time are highly associated with baseline values of the assay and vary by assay type. IMPACT: These findings suggest that assays that change more over time may warrant consideration for studies that measure later life exposures. PMID- 22665579 TI - Use of nonsteroidal anti-inflammatory drugs and risk of ovarian and endometrial cancer: the Multiethnic Cohort. AB - BACKGROUND: Chronic inflammation may play an etiologic role in ovarian and endometrial cancer, and it is hypothesized that nonsteroidal anti-inflammatory drugs (NSAID) decrease the risk of developing these malignancies. No prospective study with a large multiethnic population has explored this hypothesis. METHODS: We investigated whether NSAID use was associated with risks of ovarian and endometrial cancer in the Multiethnic Cohort Study. Medication use of at least twice a week for >=1 month was assessed at baseline. Multivariable relative risks (RR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models. RESULTS: During 13.3 years of follow-up, 275 ovarian and 620 endometrial incident cases were identified among approximately 64,000 women included in this analysis (16.5% African Americans, 30.8% Japanese, 7.7% Native Hawaiians, 18.9%, Latinas, and 26.0% whites). The RR (95% CI) for ovarian cancer associated with aspirin, non-aspirin NSAIDs, and acetaminophen were 0.87 (0.68 1.14), 0.97 (0.74-1.26), and 0.86 (0.67-1.12), respectively. The RR (95% CI) for endometrial cancer associated with aspirin, non-aspirin NSAIDs, and acetaminophen were 0.93 (0.79-1.10), 0.88 (0.74-1.05), and 0.96 (0.81-1.13), respectively. No heterogeneity across ethnic groups (P >= 0.29) or dose-response relation with increased duration of use (P(trend) >= 0.16) was observed. The results did not differ by tumor histology. CONCLUSIONS: We found no compelling evidence to support an association between the use of NSAIDs and risk of ovarian and endometrial cancers in a multiethnic population. IMPACT: It is unlikely that NSAID is involved in the etiology of endometrial and ovarian cancer. PMID- 22665580 TI - Frontiers in cancer epidemiology: a challenge to the research community from the Epidemiology and Genomics Research Program at the National Cancer Institute. AB - The Epidemiology and Genomics Research Program (EGRP) at the National Cancer Institute (NCI) is developing scientific priorities for cancer epidemiology research in the next decade. We would like to engage the research community and other stakeholders in a planning effort that will include a workshop in December 2012 to help shape new foci for cancer epidemiology research. To facilitate the process of defining the future of cancer epidemiology, we invite the research community to join in an ongoing web-based conversation at http://blog epi.grants.cancer.gov/ to develop priorities and the next generation of high impact studies. PMID- 22665581 TI - Traumatic splenectomy in a cirrhotic patient with hepatitis C and alcoholic liver disease. AB - Non-operative management is the management of choice for haemodynamically stable patients with blunt splenic injury. However, coexistent liver cirrhosis poses significant challenges as it leads to portal hypertension and coagulopathy. A 52 year-old man sustained blunt abdominal trauma causing low-grade splenic injury. However, he was found to have liver cirrhosis causing haemodynamic instability requiring emergency laparotomy. His portal hypertension led to severe bleeding only controlled by aortic pressure and subsequent splenectomy. Mortality from emergency surgery in cirrhotic patients is extremely high. Despite aggressive resuscitation, they may soon become haemodynamically unstable. Therefore, traumatic splenectomy may be inevitable in such patients with portal hypertension and splenomegaly secondary to liver cirrhosis even in low-grade injury. PMID- 22665582 TI - Complete heart block in a 5-year-old child with varicella and acute thrombocytopenic purpura. PMID- 22665583 TI - 'Wormy'form appendix. AB - Appendicitis and helminth infections are both common conditions in children. However, helminths (pinworms) infestation causing appendiceal luminal obstruction and presenting as appendicitis is uncommon. PMID- 22665584 TI - Promoting student metacognition. PMID- 22665585 TI - Changing and evolving relationships between two- and four-year colleges and universities: they're not your parents' community colleges anymore. PMID- 22665586 TI - Science denial and the science classroom. PMID- 22665587 TI - Are Africans, Europeans, and Asians different "races"? A guided-inquiry lab for introducing undergraduate students to genetic diversity and preparing them to study natural selection. AB - Many students do not recognize that individual organisms within populations vary, and this may make it difficult for them to recognize the essential role variation plays in natural selection. Also, many students have weak scientific reasoning skills, and this makes it difficult for them to recognize misconceptions they might have. This paper describes a 2-h laboratory for college students that introduces them to genetic diversity and gives them practice using hypothetico deductive reasoning. In brief, the lab presents students with DNA sequences from Africans, Europeans, and Asians, and asks students to determine whether people from each continent qualify as distinct "races." Comparison of the DNA sequences shows that people on each continent are not more similar to one another than to people on other continents, and therefore do not qualify as distinct races. Ninety-four percent of our students reported that the laboratory was interesting, and 79% reported that it was a valuable learning experience. We developed and used a survey to measure the extent to which students recognized variation and its significance within populations and showed that the lab increased student awareness of variation. We also showed that the lab improved the ability of students to construct hypothetico-deductive arguments. PMID- 22665588 TI - Short lesson plan associated with increased acceptance of evolutionary theory and potential change in three alternate conceptions of macroevolution in undergraduate students. AB - Undergraduates commonly harbor alternate conceptions about evolutionary biology; these alternate conceptions often persist, even after intensive instruction, and may influence acceptance of evolution. We interviewed undergraduates to explore their alternate conceptions about macroevolutionary patterns and designed a 2-h lesson plan to present evidence that life has evolved. We identified three alternate conceptions during our interviews: that newly derived traits would be more widespread in extant species than would be ancestral traits, that evolution proceeds solely by anagenesis, and that lineages must become more complex over time. We also attempted to measure changes in the alternate conceptions and levels of acceptance of evolutionary theory in biology majors and nonmajors after exposure to the lesson plan. The instrument used to assess understanding had flaws, but our results are suggestive of mixed effects: we found a reduction in the first alternate conception, no change in the second, and reinforcement of the third. We found a small, but significant, increase in undergraduate acceptance of evolutionary theory in two trials of the lesson plan (Cohen's d effect sizes of 0.51 and 0.19). These mixed results offer guidance on how to improve the lesson and show the potential of instructional approaches for influencing acceptance of evolution. PMID- 22665589 TI - Studying human disease genes in Caenorhabditis elegans: a molecular genetics laboratory project. AB - Scientists routinely integrate information from various channels to explore topics under study. We designed a 4-wk undergraduate laboratory module that used a multifaceted approach to study a question in molecular genetics. Specifically, students investigated whether Caenorhabditis elegans can be a useful model system for studying genes associated with human disease. In a large-enrollment, sophomore-level laboratory course, groups of three to four students were assigned a gene associated with either breast cancer (brc-1), Wilson disease (cua-1), ovarian dysgenesis (fshr-1), or colon cancer (mlh-1). Students compared observable phenotypes of wild-type C. elegans and C. elegans with a homozygous deletion in the assigned gene. They confirmed the genetic deletion with nested polymerase chain reaction and performed a bioinformatics analysis to predict how the deletion would affect the encoded mRNA and protein. Students also performed RNA interference (RNAi) against their assigned gene and evaluated whether RNAi caused a phenotype similar to that of the genetic deletion. As a capstone activity, students prepared scientific posters in which they presented their data, evaluated whether C. elegans was a useful model system for studying their assigned genes, and proposed future directions. Assessment showed gains in understanding genotype versus phenotype, RNAi, common bioinformatics tools, and the utility of model organisms. PMID- 22665590 TI - A simple microscopy assay to teach the processes of phagocytosis and exocytosis. AB - Phagocytosis and exocytosis are two cellular processes involving membrane dynamics. While it is easy to understand the purpose of these processes, it can be extremely difficult for students to comprehend the actual mechanisms. As membrane dynamics play a significant role in many cellular processes ranging from cell signaling to cell division to organelle renewal and maintenance, we felt that we needed to do a better job of teaching these types of processes. Thus, we developed a classroom-based protocol to simultaneously study phagocytosis and exocytosis in Tetrahymena pyriformis. In this paper, we present our results demonstrating that our undergraduate classroom experiment delivers results comparable with those acquired in a professional research laboratory. In addition, students performing the experiment do learn the mechanisms of phagocytosis and exocytosis. Finally, we demonstrate a mathematical exercise to help the students apply their data to the cell. Ultimately, this assay sets the stage for future inquiry-based experiments, in which the students develop their own experimental questions and delve deeper into the mechanisms of phagocytosis and exocytosis. PMID- 22665591 TI - Does instructor type matter? Undergraduate student perception of graduate teaching assistants and professors. AB - Graduate teaching assistants (GTAs) are used extensively as instructors in higher education, yet their status and authority as teachers may be unclear to undergraduates, to administrators, and even to the GTAs themselves. This study explored undergraduate perception of classroom instruction by GTAs and professors to identify factors unique to each type of instructor versus the type of classes they teach. Data collection was via an online survey composed of subscales from two validated instruments, as well as one open-ended question asking students to compare the same class taught by a professor versus a GTA. Quantitative and qualitative results indicated that some student instructional perceptions are specific to instructor type, and not class type. For example, regardless of type of class, professors are perceived as being confident, in control, organized, experienced, knowledgeable, distant, formal, strict, hard, boring, and respected. Conversely, GTAs are perceived as uncertain, hesitant, nervous, relaxed, laid back, engaging, interactive, relatable, understanding, and able to personalize teaching. Overall, undergraduates seem to perceive professors as having more knowledge and authority over the curriculum, but enjoy the instructional style of GTAs. The results of this study will be used to make recommendations for GTA professional development programs. PMID- 22665592 TI - A 29-year-old renal transplant recipient with acute respiratory failure. PMID- 22665593 TI - A randomized controlled trial of the plastic-housing BioSand filter and its impact on diarrheal disease in Copan, Honduras. AB - Point of use drinking water treatment with the BioSand filter (BSF) allows people to treat their water in the home. The purpose of this research was to document the ability of the Hydraid plastic-housing BSF to reduce diarrheal disease in households who received a BSF in a randomized controlled trial. The trial of the Hydraid plastic-housing BSF was carried out in rural, mountainous communities in Copan, Honduras during April of 2008 to February of 2009. A logistic regression adjusting for clustering showed that the incidence of diarrheal disease in children under 5 years was reduced by approximately 45% (odds ratio = 0.55, 95% confidence interval = 0.28, 1.10) in households that had a BSF compared with those households without a BSF, but this finding fluctuated depending on season and was not statistically significant. Households with a BSF had significantly better drinking water quality regardless of water source or season. PMID- 22665594 TI - Use of commercially available oral rehydration solutions in Lima, Peru. AB - Caregivers' practices concerning oral rehydration of young children during diarrheal illness were investigated in a periurban community of low socioeconomic level in Lima, Peru. Data of 330 caregivers of children aged 6-36 months were analyzed; 72.7% of all caregivers would give commercially available oral rehydration solutions (ORSs). However, only 58.6% of those caregivers with children that had experienced diarrhea during the previous week stated that they had used commercially available ORSs, a significantly lower percentage. The main reason for not using commercially available ORSs was that caregivers did not know about them. Of all recipes caregivers provided for homemade ORS, none contained the recommended concentrations of sugar and salt. Educating caregivers about availability, benefits, and use of commercially available ORSs as well as correct preparation of homemade ORS is urgently needed. PMID- 22665595 TI - Contributions of polyclonal malaria, gametocytemia, and pneumonia to infant severe anemia incidence in malaria hyperendemic Pemba, Tanzania. AB - The causative factors for severe anemia incidence in sub-Saharan Africa are multifactorial. In an observational, longitudinal study of two cohorts of about 300 infants followed-up for six months in a malaria hyperendemic area, the risk factors for severe anemia incidence were clinical malaria and pneumonia, which outweighed nutritional and sociodemographic factors. Severe anemia incidence was 1-2/year at age 2 months, peaked around 6-7/year at age 7-12 months, and decreased back to 1-2/year at age 16-22 months. The age-dependent increase of severe anemia incidence was shown to be parallel to the age-dependent increase of clinical malaria. Previous clinical malaria episodes increased the severe anemia risk by 80%, and gametocyte carriage and pneumonia at prior visit was associated with a six-fold increase and a > 10-fold increase, respectively. The role of pneumonia and malaria as risk factors, and areas for interventions for severe anemia, should not be underestimated. PMID- 22665596 TI - Use of a rhesus Plasmodium cynomolgi model to screen for anti-hypnozoite activity of pharmaceutical substances. AB - There remains a need for new drugs to prevent relapse of Plasmodium vivax or P. ovale infection. The relapsing primate malaria P. cynomolgi has been used for decades to assess drugs for anti-hypnozoite activity. After sporozoite inoculation and blood-stage cure of initial parasitemia with chloroquine, rhesus macaques were treated on subsequent relapses with chloroquine in conjunction with test regimens of approved drugs. Tested drugs were selected for known liver or blood-stage activity and were tested alone or in conjunction with low-dose primaquine. Tinidazole and pyrazinamide prevented relapse when used in conjunction with chloroquine and low-dose primaquine. Triamterene and tinidazole administered without primaquine achieved radical cure in some animals. All other tested drugs or combinations failed to prevent relapse. The rhesus macaque-P. cynomolgi model remains a useful tool for screening drugs with anti-hypnozoite activity. Tinidazole and pyrazinamide require further investigation as agents to enable dose reduction of primaquine. PMID- 22665597 TI - Pregnancy outcomes among patients with sickle cell disease at Korle-Bu Teaching Hospital, Accra, Ghana: retrospective cohort study. AB - Pregnancy in sickle cell disease (SCD) patients is associated with increased risk of maternal and fetal mortality. This study determines pregnancy outcomes among women with SCD delivering at Korle-Bu Teaching Hospital, Accra, Ghana. Nine hundred sixty (960) medical records of pregnant women (131 HbSS, 112 HbSC, and 717 comparison group) from 2007 to 2008 were reviewed. The HbSS women were at increased risk of eclampsia (adjusted odds ratio [AOR] = 10.56, 95% confidence interval [CI] = 3.60-30.96, P < 0.001), intrauterine growth restriction (AOR = 4.00, 95% CI = 1.38-11.64, P = 0.011), and placenta previa (AOR = 22.03, 95% CI = 9.87-49.14, P < 0.001) compared with the comparison group. The HbSC women had increased risk for intrauterine fetal death (AOR = 3.38, 95% CI = 1.15-9.96, P = 0.027) and decreased risk of delivering low birth weight babies (AOR = 0.21, 95% CI = 0.06-0.73, P = 0.014). Women with SCD in Ghana are at a greater risk of morbidity and mortality in pregnancy compared with women without hemoglobinopathies. Improved maternal and fetal outcomes in Ghanaian women with SCD can be achieved through effective intervention by health care providers with thorough knowledge about predisposing factors toward adverse outcomes. PMID- 22665598 TI - PFE0565w, a Plasmodium falciparum protein expressed in salivary gland sporozoites. AB - Because malaria is still a significant problem worldwide, additional control methods need to be developed. The Plasmodium sporozoite is a good target for control measures because it displays dual infectivity for both mosquito and vertebrate host tissues. The Plasmodium falciparum gene, PFE0565w, was chosen as a candidate for study based on data from PlasmoDB, the Plasmodium database, indicating that it is expressed both at the transcriptional and protein levels in sporozoites, likely encodes a putative surface protein, and may have a potential role in the invasion of host tissues. Additional sequence analysis shows that the PFE0565w protein has orthologs in other Plasmodium species, but none outside of the genus Plasmodium. PFE0565w expresses transcript during both the sporozoite and erythrocytic stages of the parasite life cycle, where an alternative transcript was discovered during the erythrocytic stages. Data show that transcript is not present during axenic exoerythrocytic stages. Despite transcript being present in several life cycle stages, the PFE0565w protein is present only during the salivary gland sporozoite stage. Because the PFE0565w protein is present in salivary gland sporozoites, it could be a novel candidate for a pre-erythrocytic stage vaccine. PMID- 22665599 TI - Low prevalence of Leishmania infection in post-epidemic areas of Libo Kemkem, Ethiopia. AB - In Libo Kemkem (a district of Amhara region, Ethiopia), no cases of kala-azar had ever been reported until 2005 when an outbreak occurred. Over one-third of those cases were children under 15 years of age. The aim of the present study was to determine the prevalence of Leishmania infection in children aged 4-15 years. A cross-sectional survey was conducted in 2009. Children participating in the survey were selected using a three-stage cluster sampling method. A total of 386 children were included in the study. The overall prevalence of Leishmania infection (direct agglutination test- and/or rK39 immunochromatographic test- and/or leishmanin skin test-positive subjects) in this population was 1.02% (95% confidence interval = 0-4.54), and prevalence was higher in boys and children older than 12 years. Only one case of active disease was encountered. The results suggest that the conditions responsible for the outbreak no longer reign. However, active surveillance remains necessary. PMID- 22665600 TI - Clinical epidemiologic profile of a cohort of post-kala-azar dermal leishmaniasis patients in Bihar, India. AB - Post-kala-azar dermal leishmaniasis (PKDL) has important public health implications for transmission of visceral leishmaniasis (VL). Clinical and epidemiologic profiles of 102 PKDL patients showed that median age of males and females at the time of diagnosis was significantly different (P = 0.013). A significant association was observed between family history of VL and sex of PKDL patients (chi(2) = 5.72, P < 0.01). Nearly 33% of the patients showed development of PKDL within one year of VL treatment. The observed time (median = 12 months) between appearance of lesions and diagnosis is an important factor in VL transmission. A significant association was observed between type of lesions and duration of appearance after VL treatment (chi(2) = 6.59, P = 0.001). Because PKDL was observed during treatment with all currently used anti-leishmanial drugs, new drug regimens having high cure rates and potential to lower the PKDL incidence need to be investigated. PMID- 22665601 TI - Natural infection of North African gundi (Ctenodactylus gundi) by Leishmania tropica in the focus of cutaneous leishmaniasis, Southeast Tunisia. AB - North African gundis (Ctenodactylus gundi) were trapped in the Leishmania (L.) tropica focus of cutaneous leishmaniasis, situated in southeast Tunisia and evaluated for Leishmania infection by real-time kinetoplast DNA polymerase chain reaction (PCR). Species identification was performed by internal transcribed spacer one (ITS1)-PCR-restriction fragment length polymorphism (RFLP) and high resolution melting (HRM) analysis of the 7SL RNA gene. Real-time PCR on blood was positive in 6 of 13 (46.2%) tested gundis. Leishmania tropica was identified in five infected gundis and Leishmania major in one specimen. Alignments of the ITS 1 DNA sequences and 7S-HRM curves analysis indicated that similar genotypes were present in humans, a sandfly, and gundis from the same region suggesting a potential role of this rodent as reservoir host of L. tropica in southeast Tunisia. PMID- 22665602 TI - The effect of removing potentially infectious dogs on the numbers of canine Leishmania infantum infections in an endemic area with high transmission rates. AB - To assess the effect of the rapid removal of potentially infectious dogs on the prevalence and incidence of canine infections, a prospective study was undertaken in an area endemic for Leishmania infantum. We used serological testing based on the rapid DPP rK28 fusion protein chromatographic immunoassay for this dog screening-and-culling intervention trial. The outcome was evaluated by measuring seropositivity and sero-conversion/-reversion rates for canine infection. Our estimates indicated that concomitant detection and elimination of seropositive dogs with active disease may affect the numbers of canine infections and disease burden temporarily, although it is insufficient as a measure to interrupt the zoonotic L. infantum transmission. However, most of the asymptomatic, seropositive dogs continuously exhibit low levels of antibodies and/or reverted, remaining seronegative thereafter. In the process of waiting for an effective vaccine, one option for canine reservoir control may be to identify these possibly genetically resistant animals and promote their expansion in the population. PMID- 22665603 TI - Chagas disease: assessing the existence of a threshold for bug infestation rate. AB - To examine the existence of a possible threshold for the domestic infestation rate of Triatoma dimidiata, below which transmission becomes unlikely, a census was conducted in 59 Chagas disease endemic communities of El Salvador and Honduras. Entomological and serological tests were conducted targeting 4,083 households and 6,324 children between 6 months and 15 years of age. The overall domestic infestation rate of Triatoma dimidiata and seroprevalence among children were 12.9% and 0.49%, respectively. Communities with a domestic infestation rate at 8% or less consistently showed a seroprevalence of 0%. In communities with a domestic infestation rate above 8%, there was a wide range in seroprevalence. A domestic infestation rate of 8% could serve as the possible threshold below which transmission would become unlikely. The implementation of an 8% threshold for determining needs for universal insecticide spraying would lead to a 21% reduction in spraying-related costs. PMID- 22665604 TI - Evaluation of a rapid point-of-care fecal antigen detection test for Entamoeba histolytica. AB - Amebiasis is a major cause of morbidity and mortality in the developing world. A reliable point-of-care test would help to improve diagnosis and early treatment. We evaluated a novel rapid fecal antigen detection test for E. histolytica (E. HISTOLYTICA QUIK CHEK; TechLab, Inc., Blacksburg, VA), in a cohort of children in Bangladesh where amebiasis is endemic. This point-of-care test had a sensitivity of 100% and a specificity of 100% when compared with enzyme-linked immunosorbent assay antigen detection. PMID- 22665605 TI - Brain magnetic resonance imaging findings in young patients with hepatosplenic schistosomiasis mansoni without overt symptoms. AB - The purpose of this study was to describe the brain magnetic resonance imaging (MRI) findings in young patients with hepatosplenic schistosomiasis mansoni without overt neurologic manifestations. This study included 34 young persons (age range = 9-25 years) with hepatosplenic schistosomiasis mansoni who had been previously treated. Patients were scanned on a 1.5-T system that included multiplanar pre-contrast and post-contrast sequences, and reports were completed by two radiologists after a consensus review. Twenty (58.8%) patients had MRI signal changes that were believed to be related to schistosomiasis mansoni. Twelve of the 20 patients had small focal hyperintensities on T2WI in the cerebral white matter, and eight patients had symmetric hyperintense basal ganglia on T1WI. There was a high frequency of brain MRI signal abnormalities in this series. Although not specific, these findings may be related to schistosomiasis. PMID- 22665606 TI - Characterization of the humoral immune response against Gnathostoma binucleatum in patients clinically diagnosed with gnathostomiasis. AB - Gnathostomiasis is an emerging systemic parasitic disease acquired by consuming raw or uncooked fresh-water fish infected with the advanced third-stage larvae of Gnathostoma spp. This disease is endemic to the Pacific region of Mexico, and one of its etiologic agents has been identified as Gnathostoma binucleatum. We characterized the humoral immune response of patients clinically diagnosed with gnathostomiasis by detecting total IgM, IgE, and IgG class and subclasses against a crude extract of the parasite by Western blotting. Our results do not show differences in the antigens recognized by IgM and IgE. However, we found that the specific humoral immune response is caused mainly by IgG, specifically IgG4. We found that 43%, 65.2%, 54.1%, and 26.3% of the patients recognize the 37-kD, 33 kD, 31-kD, and 24-kDa antigens, suggesting that the 33-kD antigen is the immunodominant antigen of G. binucleatum. PMID- 22665607 TI - Vector competence of Culex neavei (Diptera: Culicidae) for Usutu virus. AB - Usutu virus (USUV), a flavivirus belonging to the Japanese encephalitis serocomplex, was isolated for the first time from a Culex neavei mosquito in 1959 in South Africa. Despite multiple isolations of USUV from Cx. neavei in Africa, its vector competence remains unproven. Therefore, we infected Cx. neavei orally with the USUV reference strain and used reverse transcription-polymerase chain reaction and an indirect immunofluorescence assay to detect virus in bodies, legs, wings, and saliva of mosquitoes. We demonstrated the susceptibility of Cx. neavei mosquitoes for the USUV reference strain, its potential to be transmitted, and infection, dissemination, and transmission rates of 90.9%, 40.0%, and 81.3%, respectively. Also, we showed that infection rates are dependent on the virus titer of the blood meal. Given the bionomics of Cx. neavei, its role as enzootic vector for USUV in Africa in a mosquito-bird transmission cycle or as bridge vector for USUV transmission to humans is discussed. PMID- 22665608 TI - Impact of indoor residual spraying with lambda-cyhalothrin on malaria parasitemia and anemia prevalence among children less than five years of age in an area of intense, year-round transmission in Malawi. AB - Little is known about the impact of indoor residual spraying (IRS) in areas with intense malaria transmission such as sub-Saharan Africa. In Malawi, IRS with lambda-cyhalothrin has been applied annually in an area of intense year-long transmission since 2007. We evaluated the impact of IRS on parasitemia and anemia prevalence in children less than five years of age by using a cross-sectional household survey conducted in 2009, six months after the second IRS spray round. We measured malaria parasitemia and anemia (hemoglobin level < 11 g/dL) in 899 children less than five years of age and used binomial regression to assess the impact of IRS by comparing children living in a household sprayed with IRS (direct IRS) with those in a household not sprayed with IRS, but in an IRS area (indirect IRS) and those living in a household not sprayed with IRS and not in an IRS area (no IRS). In the IRS area, 77% of households reported receiving IRS. Adjusting for bed net use, house construction, and socioeconomic status, we found that receiving direct IRS and indirect IRS were significantly associated with a 33% (95% confidence interval [CI] = 1-54%) and 46% (95% CI = 20-64%) reduction in parasitemia and a 21% (95% CI = 4-34%) and 30% (95% CI = 12-45%) reduction in anemia prevalence, respectively. PMID- 22665609 TI - An insight into the sialotranscriptome of Triatoma matogrossensis, a kissing bug associated with fogo selvagem in South America. AB - Triatoma matogrossensis is a Hemiptera that belongs to the oliveirai complex, a vector of Chagas' disease that feeds on vertebrate blood in all life stages. Hematophagous insects' salivary glands (SGs) produce potent pharmacologic compounds that counteract host hemostasis, including anticlotting, antiplatelet, and vasodilatory molecules. Exposure to T. matogrossensis was also found to be a risk factor associated with the endemic form of the autoimmune skin disease pemphigus foliaceus, which is described in the same regions where Chagas' disease is observed in Brazil. To obtain a further insight into the salivary biochemical and pharmacologic diversity of this kissing bug and to identify possible allergens that might be associated with this autoimmune disease, a cDNA library from its SGs was randomly sequenced. We present the analysis of a set of 2,230 (SG) cDNA sequences, 1,182 of which coded for proteins of a putative secretory nature. PMID- 22665610 TI - Emergence of multidrug-resistant Vibrio cholerae O1 biotype El Tor in Port Blair, India. PMID- 22665611 TI - Facilitated molecular typing of Shigella isolates using ERIC-PCR. AB - To evaluate the performance of enterobacterial repetitive intergenic sequence based polymerase chain reaction (ERIC-PCR) typing versus the current standard for the typing of Shigella pulsed gel electrophoresis (PFGE), we typed 116 Shigella isolates from a village in an endemic setting over a 20-month period using both methods. PFGE identified 37 pulse types and had a discrimination index of 0.925 (95% confidence interval = 0.830-1.00), whereas ERIC-PCR identified 42 types and had a discrimination index of 0.961 (95% confidence interval = 0.886-1.00). PFGE and ERIC-PCR showed a 90.4% correlation in the designation of isolates as clonal or non-clonal in pairwise comparisons. Both systems were highly reproducible and provided highly similar and supplementary data compared with serotyping regarding the transmission dynamics of shigellosis in this community. ERIC-PCR is considerably more rapid and inexpensive than PFGE and may have a complementary role to PFGE for initial investigations of hypothesized outbreaks in resource limited settings. PMID- 22665612 TI - Naturally acquired and conjugate vaccine-induced antibody to Haemophilus influenzae type b (Hib) polysaccharide in Malian children: serological assessment of the Hib immunization program in Mali. AB - Haemophilus influenzae type b (Hib) conjugate vaccine for infants (6, 10, and 14 weeks of age) was introduced into the Malian Expanded Program on Immunization in July 2005, to diminish invasive Hib disease in young children. Antibodies to Hib capsular polysaccharide (PRP) were measured in infants and toddlers from an area already served by the Hib immunization program (Bamako) and in unimmunized children of the same age in a district (Kangaba) where Hib immunization had not yet begun. Among vaccinated Bamako children 6-23 months of age, 77-93% exhibited PRP titers >= 1.0 MUg/mL, indicating long-term protection, versus only 10-23% of Kangaba children of that age. High PRP antibody titers in immunized children persisted through 2 years of age. Moreover, ~50% of Bamako children exhibited anti-PRP titers >= 5.0 MUg/mL; a level that impedes Hib upper respiratory carriage, and may thereby diminish the Hib transmission to the unimmunized susceptible population (i.e., providing indirect protection). PMID- 22665613 TI - Leptospira and rodents in Cambodia: environmental determinants of infection. AB - We investigated infection of rodents and shrews by Leptospira spp. in two localities of Cambodia (Veal Renh, Kaev Seima) and in four types of habitat (forests, non-flooded lands, lowland rain-fed paddy fields, houses) during the wet and the dry seasons. Habitat preference was common, and rodent and shrew species were found only in houses or in rain-fed paddy fields or in forests. Among 649 small mammals trapped belonging to 12 rodent species and 1 shrew species, 71 of 642 animals tested were carriers of Leptospira according to the 16S ribosomal RNA marker used. Rodent infection was higher in low-slope locations, corresponding to rain-fed paddy fields, especially in the rainy season and in Kaev Seima. Rodents (Rattus exulans) and shrews (Suncus murinus) inhabiting households showed significantly low levels of infections, whereas rodents living in and near to forests (shrubby wasteland, orchards) showed high levels of infection. PMID- 22665614 TI - Use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis for rapid confirmation of Burkholderia pseudomallei in septicemic melioidosis. AB - Burkholderia pseudomallei was quickly identified from blood cultures collected from septicemic patients by matrix-assisted laser desorption/ionization time-of flight mass spectrometry analysis using an in-house reference library. This procedure reduced the time to definitive identification by more than 24 hours. This analysis is a useful addition to laboratory methods for early recognition of septicemic melioidosis in non-endemic settings. PMID- 22665615 TI - Mycetoma caused by Nocardia yamanashiensis, Papua New Guinea. AB - We report the first documented case of a mycetoma caused by Nocardia yamanashiensis after the initial description of this species. The 16S-rRNA gene sequence analysis was used to identify the novel species, which showed a similarity of 99.9% to the gene sequence of the type strain. The case showed both clinical non-response and reduced susceptibility in vitro to amoxicillin plus clavulanate, and it was treated successfully with trimethoprim-sulfamethoxazole and doxycycline. Given antibiotic resistance concerns, we suggest that antimicrobial susceptibility testing should be done for the majority of Nocardia species without well-established resistance patterns. PMID- 22665616 TI - Peritonitis in patients with scrub typhus. AB - Various complications have been reported in scrub typhus cases including acute respiratory distress syndrome, encephalitis, pneumonia, pericarditis, acute renal failure, and acute hepatic failure. Few studies have reported on the gastrointestinal manifestations of scrub typhus. Typical gastrointestinal manifestations in patients with scrub typhus include abdominal pain, nausea, vomiting, hematemesis, melena, and diarrhea. The two cases presented in this study are the first reported cases of peritonitis associated with scrub typhus. This study shows that scrub typhus should also be included in the differential diagnosis of peritonitis in areas where Orientia tsutsugamushi is endemic. PMID- 22665617 TI - Murine typhus in returned travelers: a report of thirty-two cases. AB - Murine typhus, caused by Rickettsia typhi and transmitted mainly by the rat fleas, Xenopsylla cheopis, has emerged in the field of travel medicine. We analyzed retrospectively the epidemiological, clinical, and biological characteristics of the 32 murine typhus cases that were diagnosed during the past 3 years at the World Health Organization Collaborative Center for Rickettsial diseases, Marseille, France. All of the cases occurred in travelers and most of them had returned from Africa (N = 13 of 32) and South-east Asia (N = 12 of 32). Exposure to rats was reported only in a few (N = 2 of 32) patients. Almost half of the cases were diagnosed in August and September. Only four patients presented the classic triad: fever, rash, and headache. Moreover, we report the first known cases of a hemophagocytic syndrome associated with this disease. Murine typhus must be considered as an etiologic agent of febrile illness in returning travelers, particularly in those with unspecific symptoms. PMID- 22665618 TI - Rickettsia felis in Ctenocephalides felis from Guatemala and Costa Rica. AB - Rickettsia felis is an emerging human pathogen associated primarily with the cat flea Ctenocephalides felis. In this study, we investigated the presence of Rickettsia felis in C. felis from Guatemala and Costa Rica. Ctenocephalides felis were collected directly from dogs and cats, and analyzed by polymerase chain reaction for Rickettsia-specific fragments of 17-kDa protein, OmpA, and citrate synthase genes. Rickettsia DNA was detected in 64% (55 of 86) and 58% (47 of 81) of flea pools in Guatemala and Costa Rica, respectively. Sequencing of gltA fragments identified R. felis genotype URRWXCal(2) in samples from both countries, and genotype Rf2125 in Costa Rica. This is the first report of R. felis in Guatemala and of genotype Rf2125 in Costa Rica. The extensive presence of this pathogen in countries of Central America stresses the need for increased awareness and diagnosis. PMID- 22665619 TI - Possible links between sickle cell crisis and pentavalent antimony. AB - For over 60 years, pentavalent antimony (Sb(v)) has been the first-line treatment of leishmaniasis. Sickle cell anemia is a disease caused by a defect in red blood cells, which among other things can cause vasooclusive crisis. We report the case of a 6-year-old child with leishmaniasis who during treatment with meglumine antimoniate developed a sickle cell crisis (SCC). No previous reports describing the relationship between antimonial drugs and sickle cell disease were found. Reviews of both the pathophysiology of SCC and the mechanism of action of Sb(v) revealed that a common pathway (glutathione) may have resulted in the SCC. ChemoText, a novel database created to predict chemical-protein-disease interactions, was used to perform a more expansive and systematic review that was able to support the association between glutathione, Sb(v), and SCC. Although suggestive evidence to support the hypothesis, additional research at the bench would be needed to prove Sb(v) caused the SCC. PMID- 22665620 TI - Geographic variation in the relationship between human Lyme disease incidence and density of infected host-seeking Ixodes scapularis nymphs in the Eastern United States. AB - Prevention and control of Lyme disease is difficult because of the complex biology of the pathogen's (Borrelia burgdorferi) vector (Ixodes scapularis) and multiple reservoir hosts with varying degrees of competence. Cost-effective implementation of tick- and host-targeted control methods requires an understanding of the relationship between pathogen prevalence in nymphs, nymph abundance, and incidence of human cases of Lyme disease. We quantified the relationship between estimated acarological risk and human incidence using county level human case data and nymphal prevalence data from field-derived estimates in 36 eastern states. The estimated density of infected nymphs (mDIN) was significantly correlated with human incidence (r = 0.69). The relationship was strongest in high-prevalence areas, but it varied by region and state, partly because of the distribution of B. burgdorferi genotypes. More information is needed in several high-prevalence states before DIN can be used for cost effectiveness analyses. PMID- 22665621 TI - Dengue outbreak in Hadramout, Yemen, 2010: an epidemiological perspective. AB - We analyzed surveillance data of a dengue outbreak (2010) reported to the Hadramout Health Office (Yemen) and retrospectively analyzed dengue-related epidemiological and entomological events reported in Hadramout from 2005 to 2009. A total of 630 immunoglobulin M (IgM) -confirmed dengue cases of 982 febrile cases was reported during the period from February to June of 2010; 12 cases died, giving case fatality a rate of 1.9%. Among febrile cases, the highest proportion of dengue cases (37.3%) was reported in the 15- to 24-year-old age group. The overall attack rate was 0.89/1,000. The average number of cases reported by month over the preceding 5-year period compared with the 2010 data is consistent with endemicity of dengue in the region and supports epidemic designation for the dengue activity in 2010. Recognition of endemic dengue transmission and potential for substantial dengue epidemics highlight the need for consistent laboratory-based surveillance that can support prevention and control activities accordingly. PMID- 22665622 TI - Serologic study of pig-associated viral zoonoses in Laos. AB - We conducted a serologic survey of four high-priority pig-associated viral zoonoses, Japanese encephalitis virus (JEV), hepatitis E virus (HEV), Nipah virus (NiV), and swine influenza virus (SIV), in Laos. We collected blood from pigs at slaughter during May 2008-January 2009 in four northern provinces. Japanese encephalitis virus hemagglutination inhibition seroprevalence was 74.7% (95% confidence interval [CI] = 71.5-77.9%), JEV IgM seroprevalence was 2.3% (95% CI = 1.2-3.2%), and HEV seroprevalence was 21.1% (95% CI = 18.1-24.0%). Antibodies to SIV were detected in 1.8% (95% CI = 0.8-2.8%) of pigs by screening enzyme-linked immunosorbent assay, and only subtype H3N2 was detected by hemagglutination inhibition in two animals with an inconclusive enzyme-linked immunosorbent assay result. No NiV antibody-positive pigs were detected. Our evidence indicates that peak JEV and HEV transmission coincides with the start of the monsoonal wet season and poses the greatest risk for human infection. PMID- 22665623 TI - Yale Lyme disease risk maps are not accurate for the South in 2012. PMID- 22665627 TI - Text mining in livestock animal science: introducing the potential of text mining to animal sciences. AB - In biological research, establishing the prior art by searching and collecting information already present in the domain has equal importance as the experiments done. To obtain a complete overview about the relevant knowledge, researchers mainly rely on 2 major information sources: i) various biological databases and ii) scientific publications in the field. The major difference between the 2 information sources is that information from databases is available, typically well structured and condensed. The information content in scientific literature is vastly unstructured; that is, dispersed among the many different sections of scientific text. The traditional method of information extraction from scientific literature occurs by generating a list of relevant publications in the field of interest and manually scanning these texts for relevant information, which is very time consuming. It is more than likely that in using this "classical" approach the researcher misses some relevant information mentioned in the literature or has to go through biological databases to extract further information. Text mining and named entity recognition methods have already been used in human genomics and related fields as a solution to this problem. These methods can process and extract information from large volumes of scientific text. Text mining is defined as the automatic extraction of previously unknown and potentially useful information from text. Named entity recognition (NER) is defined as the method of identifying named entities (names of real world objects; for example, gene/protein names, drugs, enzymes) in text. In animal sciences, text mining and related methods have been briefly used in murine genomics and associated fields, leaving behind other fields of animal sciences, such as livestock genomics. The aim of this work was to develop an information retrieval platform in the livestock domain focusing on livestock publications and the recognition of relevant data from cattle and pigs. For this purpose, the rather noncomprehensive resources of pig and cattle gene and protein terminologies were enriched with orthologue synonyms, integrated in the NER platform, ProMiner, which is successfully used in human genomics domain. Based on the performance tests done, the present system achieved a fair performance with precision 0.64, recall 0.74, and F(1) measure of 0.69 in a test scenario based on cattle literature. PMID- 22665628 TI - Benchmarking study of industry practices during commercial long haul transport of cattle in Alberta, Canada. AB - The objective of the present study was to document current commercial practices during long haul transport (>=400 km) of cattle in Alberta through surveys delivered to truck drivers (6,152 journeys that transported 290,362 animals). The live beef export industry to the United States (89% of all journeys) had a large influence on long haul transport. This was particularly true for fat cattle going to slaughter (82%) and backgrounded feeders going to feed yards (15%). Most drivers had either limited (31% with < 2 yr) or extensive (35% > 10 yr) experience hauling cattle. The type of tractors and trailers used most frequently were those with more number of axles (quad-axle trailers pulled with push tractors) because they can accommodate extra weight. Mean (+/- SD) distance travelled was 1,081 +/- 343 km (maximum of 2,560 km) whereas time animals spent on truck averaged 15.9 +/- 6.3 h with a maximum of 45 h. However, only 5% of all journeys were greater than 30 h. The most frequent cause of delay was at the Canada-United States border crossing due to paperwork and veterinary inspections. Border delays occurred on 77% of all journeys which had a mean of 1.3 +/- 1.9 h and up to 15-h long. Driver rest stops and waiting to unload cattle at destination were the second most frequent and longest cause of delay. Ambient temperature across all journeys ranged from -42 to 45 degrees C with a mean value of 18 +/- 11.8 degrees C while temperature variation within a journey was from 0 to 46 degrees C with mean value of 15 +/- 6.6 degrees C. The proportion of dead, non-ambulatory, and lame cattle for all journeys was 0.011, 0.022, and 0.011%, respectively. The cattle transport industry showed compliance with federal regulations and to a lesser extent with recommendations. Findings showed extreme values and very large variability in transport conditions however further research is needed to assess their impact on animal welfare outcomes. Delays within the journey as a result of border crossing, weather conditions, time on truck, shrink and space allowance may play an important role in improving cattle welfare during long haul transport. PMID- 22665631 TI - Effect of exposing rams to a female stimulus before semen collection on ram libido and semen quality. AB - Rams with strong libido and desirable semen characteristics can provide more insemination doses per ejaculate and produce more progeny, improving population genetic linkage to improve the accuracy of EBV. The objective of this study was to determine if teasing rams, either by sight and smell alone (Exp. 1), or physical contact (Exp. 2), could improve libido and semen quality of rams. In Exp. 1, there were 3 treatments in which rams were exposed to the sight and smell of the ewe for 1 h: control treatment (n = 5) in which rams were exposed to a ewe not in estrus; non-novel treatment (n = 6) in which rams were exposed to a ewe in estrus and the same ewe was used for semen collection; and novel treatment (n = 6) in which rams were exposed to a ewe in estrus and a different ewe in estrus was used for semen collection. In Exp. 2, rams were individually given full access to a ewe, which had a cotton apron fitted to cover her vulva, for 15 min. The 3 treatments in Exp. 2 were: control treatment (n = 5) in which rams were placed in a pen with a ewe not in estrus; a non-novel treatment (n = 5) in which rams were placed in a pen with a ewe in estrus and the same ewe was used for semen collection; novel treatment (n = 6) in which rams were placed in a pen with a ewe in estrus and a different ewe in estrus was used for semen collection. Experiment 1 was repeated for 5 consecutive days and Exp. 2 was repeated for 4 consecutive days. Data on reaction time, number of mounts, semen volume, semen concentration, sperm wave motion, and progressive linear motion (Exp. 1 only) were collected and analyzed as a randomized complete block design, where rams were initially blocked for breed and age. In Exp. 1, there was an effect of day (P < 0.05) and a treatment * day interaction (P < 0.05) on semen volume, whereas there was also an effect of treatment (P < 0.05) and day (P < 0.01) on semen concentration, which was most evident on d 1. In Exp. 2, there was an effect of treatment on reaction time (P < 0.05) and semen volume (P = 0.08), which was most evident on d 1. This study demonstrates an acute effect on d 1 on semen concentration when rams were exposed to the sight and smell of a ewe in estrus. Alternatively, when rams were stimulated with physical contact of a ewe in estrus, an acute increase in semen volume was evident on d 1. These effects were not evident on subsequent days and thus the overall benefits on ram libido and semen quality of exposing rams to ewes in estrus are minimal. PMID- 22665632 TI - A methodological approach to estimate the lactation curve and net energy and protein requirements of beef cows using nonlinear mixed-effects modeling. AB - The objective of this study was to evaluate methods to predict the secretion of milk and net energy and protein requirements of beef cows (Bos indicus and B. taurus) after approximately 1 mo postpartum using nonlinear mixed-effect modeling (NLME). Twenty Caracu * Nellore (CN) and 10 Nellore (NL) cows were inseminated to Red Angus bulls, and 10 Angus * Nellore (AN) were bred to Canchim bulls. Cows were evaluated from just after calving (25 +/- 11 d) to weaning (220 d). Milk yield was estimated by weighing calves before and after suckling (WSW) and by machine milking (MM) methods at 25, 52, 80, 109, 136, 164, 193, and 220 +/- 11 d of lactation. Brody and simple linear equations were consecutively fitted to the data and compared using information criteria. For the Brody equation, a NLME model was used to estimate all lactation profiles incorporating different sources of variation (calf sex and breed of cow, cow as a nested random effect, and within-cow auto-correlation). The CV for the MM method (29%) was less than WSW (45%). Consequently, the WSW method was responsible for reducing the variance about 1.5 times among individuals, which minimized the ability to detect differences among cows. As a result, only milk yield MM data were used in the NLME models. The Brody equation provided the best fit to this dataset, and inclusion of a continuous autoregressive process improved fit (P < 0.01). Milk, energy and protein yield at the beginning of lactation were affected by cow genotype and calf sex (P < 0.001). The exponential decay of the lactation curves was affected only by genotype (P < 0.001). Angus * Nellore cows produced 15 and 48% more milk than CN and NL during the trial, respectively (P < 0.05). Caracu * Nellore cows produced 29% more milk than NL (P < 0.05). The net energy and net protein requirements for milk yield followed a similar ranking. Male calves stimulated their dams to produce 11.7, 11.4, and 11.9% more milk, energy and protein, respectively (P < 0.05). The MM method is better than the WSW technique to detect genetic or environmental differences in milk yield among beef cows. The data obtained by the MM method and analyzed by NLME models allows the inclusion of fixed effects, random effects and an auto-regressive process in lactation equations to describe lactation curves and net energy and protein requirements. The NLME is a powerful tool to describe differences in the secretion of milk due to heterosis and cell mammary external stimulus in beef cows. PMID- 22665633 TI - Early postmortem gene expression and its relationship to composition and quality traits in pig Longissimus dorsi muscle. AB - An mRNA expression study has been performed in 20- to 25-min postmortem-obtained samples from Longissimus dorsi muscle of 59 Duroc * Landrace/ Large White (LD/LW) pigs to search for gene sequences related to meat quality (pH(24), pH(45), "Lab" color coordinates, curing yield, and exudation at 3 different times) or meat composition [intramuscular fat, content of several fatty acids (C16:0, C18:0, C18:1, and C18:2), ratio of saturated, monounsaturated, and polyunsaturated fatty acids, and protein and humidity contents] traits to find targets for selection. Gene ontology analysis, biological pathway, and gene network studies all show that many more differentially expressed genes (506 vs. 279) are related to meat quality (Group P or perimortem characters) than to meat composition traits (Group L or whole life traits). The difference between the number of gene ontology terms annotated, biological pathways, and gene networks in groups P and L is notable due to the differences in the complexity of the "generation process" of P-traits and involvement of other tissues or organs in the generation of variability of L traits. Also, interactions between differentially expressed genes were found in extracellular matrix (ECM)-receptor interaction, tumor growth factor (TGF)-beta signaling pathway, fatty acid elongation in mitochondria, and adipocytokine signaling pathway, indicating that a substantial fraction of the gene networks could be associated with interactions between differentially expressed genes related to traits under study. A large number of the most overexpressed genes are related to muscle development and functionality and repair mechanisms; they could be good candidates for breeding programs in which the main goal is to enhance meat quality. PMID- 22665634 TI - Plane of nutrition by tick-burden interaction in cattle: effect on growth and metabolism. AB - Ticks are external parasites, which pose a significant economic burden to domestic animal agriculture. The effects of ticks on grazing animals may be exacerbated during periods of low nutrition, such as those encountered during drought. It is not completely understood how plane of nutrition and tick burden interact to affect metabolism in cattle. The objective of the current research was to examine the plane of nutrition by tick-burden interaction in cattle and determine the effects of this interaction on physiological indicators of growth and metabolism. Eight-month-old Angus cross steers (n = 28, 194 +/- 3.0 kg) were stratified by pretrial BW and DMI into 1 of 4 groups (n = 7/group) in a 2 * 2 factorial arrangement. Categories were: moderate (14.0 +/- 1.0% CP, 60 +/- 1.5% TDN) vs. low (9.0 +/- 1.0% CP, 58 +/- 1.5% TDN) plane of nutrition and control (no tick) vs. tick treatment (300 pair of adult Amblyomma americanum per treated animal). Steers were individually fed their respective experimental diets ad libitum and feed intake was monitored for 35 d before and 21 d after the start of tick infestation (d 0). Blood samples were harvested via coccygeal venipuncture on d -7, 0, 7, 8, 9, 10, 11, 13, 17, and 21. Plasma cortisol and IGF-I were determined by RIA. Metabolic indicators were determined by colorimetric assay. Steers weighed 195 +/- 6 kg on d -35, but on d -7 and d 21, the moderate steers weighed more than the low steers (244.1 +/- 8.7 vs. 227.7 +/- 8.4 kg, P < 0.07; and 283.4 +/- 8.0 vs. 244.0 +/- 7.9 kg, P < 0.001, respectively). Cortisol was affected by plane of nutrition and treatment (P < 0.08). Insulin-like growth factor-I was greater (P < 0.01) in moderate than in low and control animals (P < 0.02), compared with tick-treated animals. Tick treatment had no effect (P > 0.05) on any of the metabolites measured in this study. Plane of nutrition affected (P < 0.02) albumin, blood urea nitrogen, and glucose in that values from the moderate group animals were greater than those from the low group. Although cortisol was related to both tick treatment and nutritional status in the current study, with respect to the combination of parasitism and suboptimal nutrition, IGF-I was the most highly indicative constituent measured. Tick burden affected various characteristics of growth and metabolism in these growing cattle and the effects were exacerbated by a low plane of nutrition. PMID- 22665635 TI - Docosahexaenoic acid in the goat kid diet: effects on immune system and meat quality. AB - The effect of dietary docosahexaenoic acid (C22:6n3; DHA) supplementation on meat quality and immunity in goat (Capra hircus) kids was examined. Goat kids (n = 30) were fed 1 of 3 experimental diets: goat milk (GM), cow (Bos taurus) milk (CM), and CM supplemented with DHA (CM-DHA). Animals were fed ad libitum twice daily and weighed twice each week. Blood samples were collected by jugular venipuncture daily during the first 10 d of life and were subsequently collected every 5 d until slaughter at a BW of 8 kg. Carcass size (linear measurements) and weight, as well as meat pH, color, tenderness, and chemical composition were determined. Fatty acid profiles of intramuscular, peri-renal, pelvic, subcutaneous, and intermuscular fats were analyzed. Blood IgG and IgM concentrations, complement system activity (classical and alternative pathways), and chitotriosidase activity were recorded. Results indicated that the diet containing DHA did not affect (P > 0.05) carcass linear measurements, meat quality characteristics, or proximate composition of the meat. However, C22:6n3 fatty acid levels, mainly in intramuscular fat, were enriched (P < 0.05) in CM-DHA animals, and the n-6 to n-3 PUFA ratio was improved (P < 0.05). No differences (P > 0.05) in immune function were observed among groups. In conclusion, powdered whole CM is an effective option for feeding goat kids, and the inclusion of DHA to CM increases the quantity of this fatty acid in the meat. PMID- 22665636 TI - Effects of diet source and vaccination for porcine circovirustype 2 and Mycoplasma hyopneumoniae on nursery pig performance. AB - Two experiments were conducted to evaluate the effect of nursery diet sources, porcine circovirustype 2 (PCV2) and Mycoplasma hyopneumoniae (M. hyo) vaccines, and vaccination timing on pig (Sus scrofa) performance. In Exp. 1, a total of 400 pigs (5.6 BW, 1.03 kg SD) were used in a 20-d study. Treatments were arranged in a 4 * 2 factorial in a blocked design (5 pigs/pen and10 pens/treatment), with main effects of diet manufacturing source (A, B, C, or D) and vaccination timing (d 0 or 8). On either d 0 (weaning) or 8, pigs received 2 vaccines (Circumvent PCV, Intervet/Schering-Plough Animal Health, Millsboro, DE; and RespiSure One, Pfizer Animal Health, New York, NY). A pre-determined amount of segregated early weaning (SEW) diet (0.45 kg/pig) was fed followed by a transition diet until d 8, and a common diet from d 8 to 20. Diet source affected (P < 0.001) ADG during the first 4 d and affected (P <= 0.02) ADG and ADFI from d 4 to 8. There were no differences (P >= 0.18) among diet sources once pigs were fed a common diet (d 8 to 20). Overall, diet source did not affect ADG; but ADFI tended (P = 0.06) to be decreased for pigs fed Diet C compared with those fed Diets A, B, and D. Pigs vaccinated on d 0 had decreased (P <= 0.01) ADG and ADFI (d 4 to 8 and d 0 to 8), resulting in lighter (P = 0.003) BW on d 8 than those of pigs not yet vaccinated (d 8). However, overall ADG was not affected by vaccination timing. In Exp. 2, 360 pigs (5.9 SD, 0.91 kg BW) were used in a 35-d trial to evaluate the effects of different vaccines. Treatments were arranged in a 3 by 2 factorial in a blocked design (5 pigs/pen and 12 pens/treatment). Main effects included PCV2 vaccine (none; CircoFLEX, Boehringer Ingelheim Vetmedica Inc., St. Joseph, MO; or Circumvent PCV); with or without M. hyo vaccine (RespiSure, Pfizer Animal Health, New York, NY). Overall, pigs vaccinated with Circumvent PCV had decreased (P < 0.02) ADG and ADFI compared with CircoFLEX-vaccinated or control pigs. On d 35, pigs vaccinated with Circumvent PCV weighed less (P < 0.01) than CircoFLEX vaccinated or control pigs. RespiSure-vaccinated pigs had decreased (P <= 0.05) ADG compared with control pigs from d 14 to 21 and d 21 to 29. On d 35, RespiSure vaccinated pigs tended (P = 0.06) to weigh and consume less than control pigs. These data indicate diet source and vaccination timing affects pig performance after weaning. Vaccination for PCV2 and M. hyo independently reduced ADG and ADFI, but the effect was product-dependent. PMID- 22665638 TI - Chromium supplementation alters the performance and health of feedlot cattle during the receiving period and enhances their metabolic response to a lipopolysaccharide challenge. AB - Crossbred steers (n = 180; 230 +/- 6 kg) were fed during a 56-d receiving period to determine if supplementing chromium (Cr; KemTRACE Chromium Propionate 0.04%, Kemin Industries) would improve feedlot performance and health of newly-received cattle. A completely randomized block design (36 pens; 9 pens/treatment; 5 steers/pen) was used. Chromium premixes were supplemented to add 0 (Con), 0.1, 0.2, or 0.3 mg/kg of Cr to the total diet on a DM basis. No differences were detected on d 0 or after the first 14 d on feed. From d 0 to d 28, DMI (P = 0.07) and ADG increased linearly (P = 0.04) as Cr concentrations increased. From d 0 to d 56, BW (P = 0.08) displayed a tendency to increase linearly, and consequently ADG and G:F increased linearly (P <= 0.05) as Cr concentrations increased. The number of steers treated at least once for respiratory symptoms tended (P = 0.07) to linearly decrease as Cr concentrations increased. Twenty additional steers (235 +/- 4 kg) were fed 56 d to determine if supplementing Cr (Con or 0.2 mg/kg Cr) would alter the metabolic response of newly-received cattle to a lipopolysaccharide (LPS) challenge. Cattle were fitted with jugular catheters on d 52. On d 55, blood samples were collected at 0.5-h intervals from -2 to 8 h, and again at 24 h relative to a LPS challenge (0.5 MUg/kg BW) at 0 h. Serum glucose, insulin, and NEFA concentrations were determined from blood samples. Steer BW was also measured at cannulation, and 24 h and 8 d post-LPS. Steer BW did not differ at cannulation (P = 0.37), but 24 h post-LPS, Cr-supplemented steers had lost less BW (P = 0.03). Pre-LPS glucose concentration did not differ (P = 0.97). Post-LPS, there was a time * treatment interaction (P < 0.01) such that glucose concentration peaked earlier (0.5 h) and at a greater concentrations in Cr-supplemented steers (P < 0.01). Insulin concentration did not differ between treatments pre- or post-LPS (P > 0.13). Concentration of NEFA did not differ pre-LPS (P = 0.54); but 0.5 h post-LPS Cr-treated steers produced a greater peak NEFA concentration (P < 0.04). Results of this study indicate that supplementation of Cr to the basal diet can have beneficial effects on the performance and health of newly-received steers. These data also suggest that supplementation of Cr attenuated BW loss and allowed for a quicker recovery after a LPS challenge. PMID- 22665639 TI - Hydroxymethyl lysine is a source of bioavailable lysine for ruminants. AB - Experiments were conducted to evaluate the availability to ruminants of lysine from hydroxymethyl lysine, a product potentially resistant to ruminal degradation yet able to release free lysine when subjected to the acidic environment of the abomasum. An in vitro ruminal fermentation assay that led to ammonia production from free lysine was used for initial assessments, but the hydroxymethyl lysine was inhibitory to lysine degradation at the concentrations tested in vitro; therefore, an in vivo assay with sheep, using plasma lysine concentrations as the response criterion, was used for assessment. twelve mature sheep were fed graded amounts of lysine from either a commercially available ruminally protected lysine product with known availability or from hydroxymethyl lysine. the protected lysine product provided 3 or 6 g/d of metabolizable lysine, whereas the hydroxymethyl lysine provided 3 or 6 g/d of total lysine. Plasma lysine concentrations increased linearly in response to both the ruminally protected lysine product and hydroxymethyl lysine. by slope ratio analysis, the bioavailability of lysine in hydroxymethyl lysine was estimated to be 94% of that for the commercially available product. We concluded that hydroxymethyl lysine may be used as an effective means of supplementing lysine to ruminants. PMID- 22665640 TI - Effects of cecal oxytetracycline infusion, and dietary avidin and biotin supplementation on the biotin status of nongravid gilts. AB - The objective of this 49-d experiment was to test effects of cecal oxytetracycline (OTC) infusion, and dietary avidin and biotin supplementation on the biotin status of nongravid gilts. Twenty-eight crossbred gilts with an initial age of 160 d and BW of 120 kg were surgically fitted with a T-cannula in the terminal ileum, a cecal fistula, and an indwelling catheter in the anterior vena cava, and allotted to 7 dietary treatments. Treatments with the basal semipurified (SP) diet fed at 1.86 kg/d were: SP-1, negative control; SP-2, positive control with 270 MUg of biotin/kg; SP-3, with spray-dried egg albumen (EA, 100 g/d) and OTC (2.56 g/d by cecal infusion); and SP-4, with EA, OTC, and 700 MUg of biotin/kg. Treatments with the basal corn-soybean meal (CS) diet fed at 1.80 kg/d were: CS-1, negative control; CS-2, with EA and OTC; and CS-3, with EA, OTC, and 700 MUg of biotin/kg. Response criteria were: fecal bacteria counts; plasma concentrations of biotin, glucose, and urea N (PUN); liver pyruvate carboxylase (PC) activity; kidney and epithelial tissue histology; ileal and fecal biotin concentrations; ileal and total tract N and energy utilization; daily gilt observation; and BW gain. Blood samples were collected every 7 d with serial samples collected on d 49. Total urine collections and fecal grab samples were made twice daily from d 44 to 49. Gilts were killed on d 50 and liver, kidney, and skin samples were collected. No gilts had symptoms of biotin deficiency. There were no treatment differences in BW gain, plasma glucose concentrations, liver PC activity, kidney and epithelial tissue histology, or fecal bacteria counts. Ileal and total tract N and energy digestibilities (%) did not differ among treatments within the same protein source, with greater (P <= 0.05) values for gilts on the SP treatments than the CS treatments. However, N retained/N absorbed and N retained/N intake (%) were less (P <= 0.05) and PUN concentrations were greater (P <= 0.05) for SP treatments with cecal OTC infusion. The overall fecal biotin concentration mean was 2.6-fold greater than the overall ileal biotin concentration mean. In conclusion, no gilts in the current experiment became biotin deficient because the biotin requirements were met primarily by microbial synthesis and absorption of biotin from the distal small intestine and large intestine, with corn and soybean meal contributing endogenous biotin. Therefore, supplementation of diets for gilts entering the breeding herd with 100% of the current NRC biotin requirement for sows is adequate. PMID- 22665641 TI - Follicular development and expression of nuclear respiratory factor-1 and peroxisome proliferator-activated receptor gamma coactivator-1 alpha in ovaries of fetal and neonatal doelings. AB - In livestock, the ovarian reserve of follicles is established during the fetal stage. However, at least two-thirds of the oocytes present in the reserve die because of apoptosis before birth. Notably, mitochondria have been reported to play a crucial role in the fate (life/death) of oocytes. In this study, mitochondrial regulators nuclear respiratory factor-1 (NRF-1) and PPAR gamma coactivator-1 alpha (PGC-1alpha) were examined during this period of follicle development to investigate their effects on follicular development and apoptosis. Fetal and neonatal Capra haimen were used, ranging in age from 60 d postcoitum (dpc) to 30 d postpartum (dpp). Our data demonstrated that egg nests were the earliest recognizable gamete cells in ovaries of fetal and neonatal doelings. Proportions of egg nests decreased from 92.68 to 25.08% whereas single follicles increased from 7.32 to 74.92% between 60 and 120 dpc. Subsequently, between 90 and 120 dpc, the proportion of primordial follicles increased from 9.98 to 61.56% (P < 0.01). However, it did not change between 1 and 30 dpp (P = 0.12). The proportion of primary follicles increased from 1.23 to 37.93% between 90 dpc to 1 dpp (P = 0.01) but did not change between 1 and 30 dpp (P = 0.11). Meanwhile, proportions of secondary and tertiary follicles increased in an age-dependent manner. In addition, results of this study suggested that NRF-1 and PGC-1alpha proteins are mainly localized in germ cells of egg nests, cytoplasm of oocytes, and granulosa cells of follicles ranging from primordial to tertiary follicles. The transcript abundance of NRF-1 mRNA was up-regulated in 60-dpc-old ovaries compared with 1-dpp-old ovaries (P < 0.05), but the PGC-1alpha mRNA expression pattern did not change (P = 0.05). Nevertheless, the number of terminal deoxynucleotidyltransferase UTP nick-end labeling (TUNEL) positive cells and caspase-3 activity in 60-dpc-old ovaries was less than those in 1-dpp-old ovaries (P < 0.01, P = 0.01). In conclusion, our results demonstrate that the key stage of primordial follicle formation is between 90 and 120 dpc in Capra haimen. Also, this study suggests that NRF-1 and PGC-1alpha might have roles in cell apoptosis during ovarian development of fetal and neonatal Capra haimen. These results improve our understanding of apoptotic mechanisms in oogenesis and folliculogenesis. PMID- 22665642 TI - Factors affecting body weight loss during commercial long haul transport of cattle in North America. AB - The objective of the present study was to identify and quantify several factors affecting shrink in cattle during commercial long-haul transport (>=400 km; n = 6,152 journeys). Surveys were designed and delivered to transport carriers to collect relevant information regarding the characteristics of animals, time of loading, origin and destination, and loaded weight before and after transport. In contrast to fat cattle, feeder cattle exhibited greater shrink (4.9 vs. 7.9 +/- 0.2% of BW, respectively; P < 0.01), and experienced longer total transport durations (12.4 vs. 14.9 +/- 0.99, respectively; P < 0.01) due to border crossing protocols which require mandatory animal inspection. Shrink was greater (P < 0.001) for feeder cattle loaded at ranches/farms and feed yards compared with those loaded at auction markets. Cattle loaded during the afternoon and evening shrank more than those loaded during the night and morning (P < 0.05). Shrinkage was less in cattle transported by truck drivers having 6 or more years of experience hauling livestock compared with those with 5 yr or less (P < 0.05). Shrink increased with both midpoint ambient temperature (% of BW/ degrees C; P < 0.001) and time on truck (% of BW/h; P < 0.001). Temperature and time on truck had a multiplicative effect on each other because shrink increased most rapidly in cattle transported for both longer durations and at higher ambient temperatures (P < 0.001). The rate of shrink over time (% of BW/h) was greatest in cull cattle, intermediate in calves and feeder cattle, and slowest in fat cattle (P < 0.05) but such differences disappeared when the effects of place of origin, loading time, and experience of truck drivers were included in the model. Cull cattle, calves and feeder cattle appear to be more affected by transport compared with fat cattle going to slaughter because of greater shrink. Several factors should be considered when developing guidelines to reduce cattle transport stress and shrink including type of cattle, ambient temperature, transport duration, driving quality, and time and origin of loading. PMID- 22665643 TI - Genomic selection for the improvement of meat quality in beef. AB - Selection index theory was used to compare different selection strategies aiming at the improvement of meat quality in beef cattle. Alternative strategies were compared with a reference scenario with three basic traits in the selection index: BW at 200 d (W200) and 400 d (W400) and muscling score (MUSC). These traits resemble the combination currently used in the German national beef genetic evaluation system. Traits in the breeding goal were defined as the 3 basic traits plus marbling score (MARB), to depict a situation where an established breeding program currently selecting for growth and carcass yield intends to incorporate meat quality in its selection program. Economic weights were either the same for all 4 traits, or doubled or tripled for MARB. Two additional selection criteria for improving MARB were considered: Live animal intramuscular fat content measured by ultrasound (UIMF) as an indicator trait and a genomic breeding value (GEBV) for the target trait directly (gMARB). Results were used to estimate the required number of genotyped animals in an own calibration set for implementing genomic selection focusing on meat quality. Adding UIMF to the basic index increased the overall genetic gain per generation by 15% when the economic weight on MARB was doubled and by 44% when it was tripled. When a genomic breeding value for marbling could be estimated with an accuracy of 0.5, adding gMARB to the index provided larger genetic gain than adding UIMF. Greatest genetic gain per generation was obtained with the scenario containing GEBV for 4 traits (gW200, gW400, gMUSC, and gMARB) when the accuracies of these GEBV were >=0.7. Adding UIMF to the index substantially improved response to selection for MARB, which switched from negative to positive when the economic weight on MARB was doubled or tripled. For all scenarios that contained gMARB in the selection index, the response to selection in MARB was positive for all relative economic weights on MARB, when the accuracy of GEBV was >0.7. Results indicated that setting up a calibration set of ~500 genotyped animals with carcass phenotypes for MARB could suffice to obtain a larger response to selection than measuring UIMF. If the size of the calibration set is ~2,500, adding the ultrasound trait to an index containing already the GEBV would bring little benefit, unless the relative economic weight for marbling is much larger than for the other traits. PMID- 22665644 TI - Characterizing growth and carcass composition differences in pigs with varying weaning weights and postweaning performance. AB - The unprecedented increase in litter size over the last decade has led to a perceived increase in the number of fallback pigs (Sus scrofa). However, there is little peer-reviewed data available regarding the biological differences between fallback pigs and their normal cohorts. Therefore, the objective of this experiment was to identify differences in the biology and physiology, and thus the growth and metabolism, between pigs with varying weaning weights (WW) and postweaning performance. To accomplish this objective, a total of 120 barrows (PIC C22/C29 * 337) were used in growth and comparative slaughter experiments. Pigs were selected from a population of 960 weanling pigs to represent the 10% lightest, median, and heaviest pigs at weaning (n = 40 pigs per WW category). Eight pigs from each WW category were harvested on d 5 postweaning as the initial slaughter group (ISG). The remaining 96 barrows were housed in individual crates, fed ad libitum quantities of a common diet during a 27-d growth study, and were harvested on d 33 or 34 postweaning. After the completion of the live animal component of the experiment, pigs within each WW category were further stratified into the slowest, median, or fastest 33% ADG categories. This resulted in a total of 9 treatments in a nested design. Fallback pigs were designated as those belonging to the slowest ADG category from either the lightest or median WW categories. Data were analyzed using the GLIMMIX procedure of SAS with the fixed effects of WW category and WW(ADG). Although feed intake was maximized (P < 0.0001) by WW(ADG) category, feed efficiency was not different (P = 0.30). When equalized per unit of BW, WW(ADG) category greatly affected (P < 0.02) eviscerated carcass, organ, and metabolic BW, but not (P = 0.28) empty BW. There were no differences (P > 0.12) in tissue nutrient concentrations, ratios, or energy content among pigs in the growth experiment. All tissue deposition rates, which were calculated as the difference between tissue nutrient concentrations of the growth experiment and initial slaughter groups, were maximized (P < 0.0002) by WW(ADG), even when equalized per unit of BW. In conclusion, WW and ADG affect tissue accretion rates, but not feed efficiency or carcass composition in nursery pigs. PMID- 22665645 TI - Effect of diet and absence of protozoa on the rumen microbial community and on the representativeness of bacterial fractions used in the determination of microbial protein synthesis. AB - Accurate estimates of microbial synthesis in the rumen are vital to optimize ruminant nutrition. Liquid- (LAB) and solid-associated bacterial fractions (SAB) harvested from the rumen are generally considered as microbial references when microbial yield is calculated; however, factors that determine their composition are not completely understood. The aim of this study was to evaluate the effect of diet and absence or presence of rumen protozoa on the rumen microbial community. It was hypothesized that these treatments could modify the composition and representativeness of LAB and SAB. Twenty twin lambs (Ovis aries) were used; one-half of the twins were kept protozoa-free, and each respective twin sibling was faunated. At 6 mo of age, 5 animals from each group were randomly allocated to the experimental diets consisting of either alfalfa hay as the sole diet, or 50:50 mixed with ground barley grain. After 15 d of adaptation to the diet, animals were euthanized, rumen and abomasum contents were sampled, and LAB and SAB isolated. The presence of protozoa buffered the effect of diet on the rumen bacterial population. Faunated animals fed alfalfa hay had a greater abundance of F. succinogenes, anaerobic fungi and methanogens, as well as an enhanced rumen bacterial diversity. Cellulolytic bacteria were more abundant in SAB, whereas the abomasal abundance of most of the microorganisms studied was closer to those values observed in LAB. Rumen and abomasal samples showed similar bacterial DNA concentrations, but the fungal and protozoal DNA concentration in the abomasum was only 69% and 13% of that observed in the rumen, respectively, suggesting fungal and protozoal sequestration in the rumen or possible preferential degradation of fungal and protozoal DNA in the abomasum, or both. In conclusion, absence of protozoa and type of diet extensively modified the chemical composition of LAB and SAB as a consequence of changes in the microbial composition of these fractions. PMID- 22665646 TI - Evaluation of Columbia, USMARC-Composite, Suffolk, and Texel rams as terminal sires in an extensive rangeland production system: I. Ewe productivity and crossbred lamb survival and preweaning growth. AB - A 3-yr study was conducted to comprehensively evaluate Columbia, Suffolk, USMARC Composite (Composite), and Texel breeds as terminal sires in an extensive rangeland production system. The objective was to estimate breed-of-ram effects on ewe fertility, prolificacy, and dystocia, and sire breed effects on lamb survival and growth until weaning at approximately 132 d of age. Data were from 22 Columbia, 22 Composite, 21 Suffolk, and 17 Texel rams with 957 exposures to 574 adult Rambouillet ewes (3- to 7-yr-old at lambing), 908 lambings, and 1,834 lambs. Ram breed did not affect ewe fertility (mean = 94.9%; p = 0.73), total number born per ewe lambing (mean = 2.02 lambs; p = 0.20), number born alive per ewe lambing (mean = 1.90 lambs; p = 0.24), or number weaned per ewe lambing (mean = 1.45 lambs, p = 0.94). Dystocia rates were different (p = 0.01) for ewes mated to Columbia (12.2%), Composite (13.5%), Suffolk (25.7%), and Texel rams (31.9%) during 1 yr of the study, but differences among ram breeds were not repeatable (p >= 0.38) during the other 2 yr. Suffolk-sired lambs were heavier (p >= 0.02) at birth (5.5 kg) and weaning (40.3 kg) than lambs sired by the other breeds, which did not differ (p >= 0.34) for birth weight (mean = 5.3 kg). Texel-sired lambs (37.4 kg) were lighter (p >= 0.02) at weaning than Columbia- (38.8 kg) and Composite-sired (38.4 kg) lambs, which did not differ (p = 0.40) for weaning weight. Sire breed effect approached significance (p = 0.06) for lamb survival to weaning; estimated survival probabilities were 0.87 (Columbia), 0.89 (Composite), 0.93 (Suffolk), and 0.86 (Texel) for lambs reared by their birth dam. Interaction between sire breeds and birth weight affected (p < 0.001) lamb survival and revealed that lightweight Columbia- and Suffolk-sired lambs had a greater risk of death than lightweight lambs sired by Composite and Texel rams, but risk of death did not increase substantially for heavyweight lambs from any of the breeds. When mated to adult Rambouillet ewes in an extensive rangeland production system, the use of Suffolk rams is warranted to improve preweaning growth of market lambs and is not predicted to affect ewe fertility, ewe prolificacy, dystocia, or lamb survival compared with the other sire breeds we tested. PMID- 22665647 TI - Effects of a slow-release urea product on performance, carcass characteristics, and nitrogen balance of steers fed steam-flaked corn. AB - Two experiments were conducted to examine the impact of source, urea (U) or Optigen II (OP), and level of dietary NPN on performance (Exp.1) and N balance (Exp. 2) of growing cattle. Sixty Angus crossbred steers (initial BW = 353 +/- 13.9 kg) were used to evaluate performance, and fed 1 of 3 steam-flaked corn based diets: U (U(1.2), 1.2% NPN), OP (OP(1.3), 1.3% NPN), or OP without cottonseed meal (OP(3.1), 3.1% NPN). U(1.2)and OP(1.3) contained cottonseed meal and NPN as CP sources, whereas OP(3.1) contained only NPN. For Exp. 1, steers were blocked by postweaning BW and assigned to treatment (TRT) and pen within block. Body weight was collected every 14 d during the 105-d trial. Six steers from each TRT were selected based on residual feed intake (RFI) and harvested. Carcass and organ measurements were obtained. Cumulative animal performance was evaluated in 3 periods (0 to 35, 0 to 70, and 0 to 105 d) using a mixed coefficient model with initial BW as a covariate. For Exp. 2, 5 ruminally cannulated Holstein steers in a 5 * 5 Latin square design were used to evaluate N balance. Steers were fed a steam-flaked corn based diet with either no NPN, 0.75% U or N equivalent OP, or 1.5% U or N equivalent OP. Intake was measured, and feed, orts, urine, and fecal samples were obtained and composited for each steer by period. Data were analyzed using a mixed coefficient model. Orthogonal contrasts were used to evaluate differences between OP and U, and high and low level of NPN. For Exp. 1, there were no differences (P > 0.10) in initial BW, final BW, ADG, or DMI among TRT for any of the periods. However, for period 1 steers on OP(3.1) had reduced F:G than U(1.2) (5.71 kg/kg vs. 7.39 kg/kg; P = 0.03), and steers fed OP(1.3) tended to have less F:G than those fed U(1.2) (6.07 kg/kg vs. 7.39 kg/kg; P = 0.07). In period 2, OP(3.1) had reduced F:G than U(1.2) (5.58 kg/kg vs. 6.56 kg/kg; P = 0.03), but did not differ from OP(1.3) (5.97). For Exp. 2, steers fed OP tended (P = 0.09) to have less apparent N absorption than those fed U. Apparent N absorption differed (P < 0.05) for level of NPN. There were no differences (P > 0.10) in intake or digestibility among source or level of NPN. No major differences (P > 0.10) on performance and carcass composition were observed between U and OP diets. Steers had better initial F:G (Period 1 and 2) when OP was used as the only source of feed N (OP(3.1)), suggesting that OP may replace true protein feeds in finishing cattle diets, minimizing feed use with no impact on carcass quality. PMID- 22665648 TI - The investigation of ultrasound technology to measure breast muscle depth as a correlated trait to breast meat yield in turkey (Meleagris gallopavo). AB - Ultrasound measurements of muscle depth were analyzed to determine if these traits could be used to increase the rate of genetic gain in breast meat yield (BMY). Two measurements of breast depth, one taken horizontally across both breast lobes and one parallel to the keel, were captured using ultrasound. Heritabilities of muscle depth traits ranged from 0.35 to 0.70. These values were greater than heritabilities of conformation scores, which ranged from 0.25 to 0.47 within sex and line. The ultrasound traits also showed strong genetic correlations to BMY, ranging from 0.43 to 0.75, indicating that selection, using ultrasound depth as a correlated information source, could result in improved BMY. Including each ultrasound trait in a linear regression model predicting BMY increased the proportion of variation explained by the models by 0.08 to 0.17, relative to using conformation score as the only in vivo estimate. Based on results from a simulated turkey breeding program with selection pressure only on BMY, the ultrasound measures could increase the accuracy of a selection index for BMY by 0.02 to 0.16. As a result, ultrasound technology has the potential to improve the rate of genetic gain in BMY in a breeding program. PMID- 22665649 TI - Effect of a carbohydrase mixture on ileal amino acid digestibility in extruded full-fat soybeans fed to finishing pigs. AB - Extrusion technology has been used successfully to improve the nutritive value of full-fat oilseeds via shear force and heat applied during passage through the extruder, exposing more peptide bonds to enzymatic hydrolysis. However, the fibrous portion of the seeds is largely intact after extrusion. Therefore, application of carbohydrase mixtures targeting nonstarch polysaccharides might further improve the nutritive value of extruded full-fat oilseeds. This hypothesis was investigated in a study involving 6 ileal-cannulated barrows (average initial BW = 75.0 kg) fed extruded full-fat, soybean- (FFSB) based diets, without or with a carbohydrase mixture (CM) to determine apparent ileal digestibility (AID) of energy and standardized ileal digestibility (SID) of AA. The CM supplement provided 500, 50, 400, 1200, 450, and 45 units of pectinase, cellulase, mannanase, xylanase, glucanase, and galactanase, respectively, per kilogram of diet. A basal diet was formulated to contain FFSB as the sole source of AA, whereas the CM diet was formulated by supplementing the basal diet with CM. Diets contained titanium dioxide as an indigestible marker. Diets were fed in a 2-period crossover design to give 6 observations per diet. Each experimental period lasted 7 d, including a 5-d adaptation period and 2-d ileal digesta collection period. The SID of N and AA were calculated using published values for ileal endogenous N and AA losses from our laboratory. Enzyme supplementation increased (P < 0.01) AID values of DM (68.7 vs. 65.7%), GE (74.6 vs. 70.5%), and N (64.2 vs. 58.5%). Greater (P < 0.05) AID values were recorded for Leu, Met + Cys, Thr, Cys, Ser, and Tyr in the CM diet compared with the basal diet. Compared with the basal diet, the CM diet had greater SID values for N (73.7 vs. 68.6%; P < 0.01), Met + Cys (59.9 vs. 52.2%; P < 0.05), and Thr (66.3 vs. 61.2%; P < 0.05). The average SID for indispensable and total AA increased by 3.4% and 3.8% units, respectively, after enzyme supplementation. In conclusion, enzyme supplementation increased the nutritive value of extruded FFSB for finishing pigs. PMID- 22665650 TI - Impact of a long photoperiod during lactation on immune status of piglets. AB - The effects of a long photoperiod treatment around parturition and throughout lactation on immune status of piglets were studied. Sows were assigned to 2 light regimens: i) standard short photoperiod (SP, n = 17), 8 h of daily light from d 112 of gestation until d 23 of lactation; and ii) long photoperiod (LP, n = 17), 23 h of daily light from d 112 of gestation to d 4 of lactation and 16 h thereafter. In front of the crates, under the side heat lamps and behind the sow, light intensities were 59 +/- 5, 109 +/- 6, and 44 +/- 6 lx, respectively. On d 15 of lactation and at weaning (d 23), 2 piglets of similar BW per litter were selected and immunized intramuscularly with ovalbumin (OVA). Blood samples (5 mL serum and 10 mL whole blood) were taken at d 15 and d 23 of lactation, and at d 30, 37, and 44 of age after weaning to evaluate the antibody response to OVA and measure phagocytosis, lymphocyte proliferative response, and different circulating blood lymphocyte populations of piglets. Results showed that phagocytosis was increased in piglets submitted to LP (P < 0.05). A treatment * time interaction (P < 0.001) indicated that SP piglets developed a better IgG response to OVA than LP piglets. The percentage of B lymphocytes was also increased (P = 0.02) in SP piglets compared with piglets exposed to LP during lactation; the lymphocyte response to OVA tended to be enhanced (P = 0.07) over time in SP piglets. Different subpopulations of CD8+ lymphocytes were markedly increased in SP piglets at 23 d of age compared with piglets exposed to LP (treatment * time: P < 0.05). These results suggest that exposure of piglets to LP during lactation seems to reduce the capacity of piglets to develop a strong immune response to novel antigens. This may have important consequences on the ability of piglets to resist an infection after weaning. PMID- 22665651 TI - Evaluation of trace mineral source and preharvest deletion of trace minerals from finishing diets for pigs on growth performance, carcass characteristics, and pork quality. AB - Weanling crossbred pigs (Sus scrofa; 72 barrows and 72 gilts; BW = 7.4 +/- 1.1 kg) were used to evaluate dietary supplemental trace mineral (Cu, Fe, Mn, and Zn) source (inorganic vs. organic) and deletion (0, 2, 4, and 6 wk preharvest) on growth performance, carcass characteristics, and pork quality. Pigs were blocked by BW, ancestry, and sex, and randomly allotted to 24 pens, and fed a diet containing either inorganic or organic trace minerals supplemented at the 1998 NRC requirement estimates for each of 5 BW phases from 7 to 120 kg (equivalent to 14, 14, 42, 28, and 42-d periods, respectively). Two pigs were removed from each pen at the end of Phase IV (BW = 82.6 +/- 6.0 kg), and 2 other pigs were removed at the end of Phase V (BW = 128.0 +/- 8.3 kg) for collection of various tissues and for determination of carcass characteristics and pork quality. On d 1, 15, and 29 of Phase V, 3 pens within each source of minerals were switched to a common diet without supplemental trace minerals, whereas the remaining 3 pens within each source of minerals were fed diets containing trace minerals throughout the Phase V period. This resulted in 4 groups within each mineral treatment, in which trace mineral supplementation was deleted for 6, 4, 2, or 0 wk of Phase V. Trace mineral source (inorganic vs. organic) did not affect ADG, ADFI, and G:F (773 vs. 778 g/d, 1,680 vs. 1,708 g/d, and 461 vs. 456 g/kg, respectively) during the first 4 phases. During the mineral deletion period, ADG and G:F were not affected by the duration of trace mineral deletion, but ADFI increased when trace minerals were removed from the diet for 6 wk (6 vs. 0 wk, 3,393 vs. 3,163 g/d; P = 0.05). Hot carcass weight, cold carcass weight, carcass shrink, dressing percentage, LM area, 10th rib and midline average backfat, and carcass fat-free lean weight and percentage were not affected (P > 0.10) by the source of mineral or length of mineral deletion, but carcass length tended to decrease (P = 0.09) when time of trace mineral deletion increased. Increasing mineral deletion from 0 to 6 wk tended to reduce linearly (P = 0.08) Hunter a* scores on the day of carcass processing (24 h after slaughter), as well as 2 d after processing, and Hunter b* scores on d 2 and d 6 after processing. Results of this experiment indicate that use of organic trace minerals, rather than inorganic trace minerals, did not influence pig growth performance or carcass characteristics and quality; however, deletion of minerals during the last 6 wk before harvest increased ADFI and affected drip loss, some color scores of the LM, and carcass length. PMID- 22665652 TI - Effects of corn processing method and dietary inclusion of corn wet distillers grains with solubles on odor and gas production in cattle manure. AB - The growing ethanol industry in the Southern Great Plains has recently increased the use of wet distillers grains with solubles (WDGS) in beef cattle finishing diets. Two experiments were conducted to evaluate odorous compound production in urine and feces of feedlot steers fed diets with different concentrations of WDGS and different grain processing methods. In both experiments, a Latin square design was used. In Exp. 1, a 2* 2 factorial arrangement of treatments was used and the factors consisted of corn processing method [steam-flaked corn (SFC) or dry-rolled corn (DRC)] and inclusion of corn-based WDGS (0 or 30% on a DM basis). Thus, the 4 treatment combinations consisted of: 1) SFC-based diet with 0% WDGS (SFC-0); 2) SFC-based diet with 30% WDGS (SFC-30); 3) DRC-based diet with 0% WDGS (DRC-0); and 4) DRC-based diet with 30% WDGS (DRC-30). In Exp. 2, all diets were based on SFC and the 4 treatments consisted of: 1) 0% WDGS (SFC-0); 2) 15% WDGS (SFC-15); 3) 30% WDGS (SFC-30); and 4) 45% WDGS (SFC-45). In both experiments, diets were balanced for degradable intake protein and ether extract by the addition of cottonseed meal and fat. Fecal slurries were prepared from a 5-d composite of urine and feces collected from each treatment. The slurries were analyzed using a gas chromatograph for VFA, phenol, p-cresol, indole, skatole, hydrogen, methane (CH(4),) and total gas production. In Exp. 1, the DRC fecal slurries had greater initial total VFA concentration compared with the SFC-based slurries and accumulated a greater concentration of total gas throughout the incubation; however, the SFC-based manure resulted in more CH(4) production. In Exp. 2, total VFA concentrations did not differ across all fecal slurries initially and on d 28; however, throughout the incubation, slurries with 0 and 15% WDGS had the greatest total VFA concentration. Overall, the presence of starch in the feces was likely the determining factor for the accumulation of odorous compounds in the fecal slurries initially, which was especially evident in diets including DRC, and once methanogenic microorganisms were established they likely converted VFA to CH(4). PMID- 22665654 TI - Effects of monensin supplementation on ruminal metabolism of feedlot cattle fed diets containing dried distillers grains. AB - Two experiments were conducted to evaluate the effects of monensin and dried distillers grains with solubles (DDGS) on ruminal metabolism in 8 fistulated steers. In Exp. 1, treatments were (DM basis): 1) 0 mg monensin/kg diet DM, 2) 22 mg monensin/kg diet DM, 3) 33 mg monensin/kg diet DM, and 4) 44 mg monensin/kg diet DM. The remainder of the diet was 10% corn silage, 60% DDGS, 10% corn, and 20% mineral supplement that used ground corn as the carrier. There was no effect (P > 0.80) of dietary monensin inclusion on DMI. Increasing dietary monensin did not affect (P > 0.05) ruminal VFA concentrations or lactic acid concentrations. There was no effect (P > 0.15) of increasing dietary monensin concentration on ruminal hydrogen sulfide gas (H(2)S) and liquid sulfide (S(2-)) concentrations, or ruminal pH. In Exp. 2, treatments were arranged in a 2 * 2 factorial and contained (DM basis): 1) 0 mg monensin/kg diet DM + 25% DDGS inclusion, 2) 0 mg monensin/kg diet DM + 60% DDGS inclusion, 3) 44 mg monensin/kg diet DM + 25% DDGS inclusion, and 4) 44 mg monensin/kg diet DM + 60% DDGS inclusion. The remainder of the diet was 15% corn silage, corn, and 20% mineral supplement that used ground corn as a carrier. With 60% dietary DDGS inclusion, DMI decreased (P < 0.01) when compared with 25% DDGS inclusion. With 25% DDGS in the diet, 0 h postfeeding acetate concentration was decreased compared with when 60% DDGS was fed (P < 0.01). A similar response (P < 0.01) occurred for total VFA concentrations at 0 h postfeeding. However, at 3 and 6 h postfeeding, propionate concentrations increased (P <= 0.05) in cattle fed the 60% DDGS diets, regardless of monensin inclusion. This increase in propionate concentrations contributed to the increase (P = 0.03) in total VFA concentrations at 3 h postfeeding when 60% DDGS diets were fed. There was no interaction detected (P > 0.05) for H(2)S or S(2-) concentrations in Exp. 2. Feeding 60% DDGS diets increased mean H(2)S by 71% when compared with feeding 25% DDGS diets. Similar to the response observed for H(2)S, feeding 60% DDGS diets increased mean S(2-) by 64% when compared with feeding 25% DDGS diets. Although these studies did not show beneficial effects of monensin supplementation on ruminal pH, VFA, or H(2)S concentrations, adverse rumen conditions, notably low ruminal pH, when high DDGS diets were fed may have precluded the effects of monensin from being realized. PMID- 22665656 TI - Impact of moderate exercise on ovarian blood flow and early embryonic outcomes in mares. AB - The advent of embryo transfer has allowed horses to continue to train and compete during the breeding season. However, the associated stress of exercise may be detrimental to reproduction. The objectives of this study were to evaluate differing exercise protocols on reproductive blood flow and embryonic outcomes in mares. Light-horse mares were randomized into control (n = 4), partial-exercised (n = 6), and full-exercised (n = 6) groups. Partial-exercised mares were moderately exercised 30 min daily during the periovulatory period and rested after ovulation for 7 d. Full-exercised mares were exercised for 30 min daily throughout the reproductive cycle. Mares were artificially inseminated during estrus and subjected to uterine flush for embryo recovery on d 7 post ovulation. Blood flow through both ovarian arteries and vascular perfusion of the wall of the preovulatory follicle were examined by color Doppler ultrasonography. Results indicated exercise induced greater serum cortisol concentrations (P < 0.05). Embryo recovery rates were reduced in exercised (20/46, 43%) compared with control (14/21, 67%) mares (P < 0.10). When examined separately, embryo recovery rates for partial-exercised (11/25, 44%) and full-exercised (9/21, 43%) mares were not significantly different. Additionally, fewer quality Grade 1 embryos were recovered from partial-exercised mares compared with both control and full exercised mares (P < 0.05). Blood flow through both ovarian arteries was greater in both exercised groups in the days leading up to ovulation (P < 0.05). However, vascular perfusion of the wall of the preovulatory follicle on the day before ovulation was less in both partial-exercised (45.9 +/- 3.0%) and full-exercised (44.8 +/- 3.4%) mares vs. control (54.9 +/- 3.6%; P < 0.05). In exercised mares, vascular perfusion of the follicle wall was greater when an embryo was recovered (P < 0.01). No differences were found in follicle ovulatory diameter among exercised and non-exercised mares. When groups were combined, follicle diameter was greater when an embryo was recovered (44.9 +/- 1.0 mm) compared with an unsuccessful embryo recovery attempt (42.8 +/- 0.7 mm; P < 0.05). In conclusion, these data demonstrated that exercise increased ovarian arterial blood flow leading up to ovulation and decreased vascular perfusion of the wall of the preovulatory follicle. Mares given rest the day after ovulation up until an embryo collection attempt did not improve embryo recovery rates. PMID- 22665658 TI - Involvement of free cholesterol and high-density lipoprotein in development and resistance of the preimplantation bovine embryo to heat shock. AB - Development of the mammalian preimplantation embryo is susceptible to disruption by elevated temperature. The molecular and biochemical bases for developmental, genetic, and other differences in embryonic resistance to heat shock are largely not known. Here we tested the hypothesis that increasing free cholesterol content could improve embryonic resistance to heat shock. Culture of bovine embryos at 41.0 degrees C for 15 h beginning at 30 h after insemination (1- to 2-cell stage) reduced development to the blastocyst stage. Reduction in embryonic cholesterol content by culture with methyl-beta-cyclodextrin (MBCD) reduced development. This effect of MBCD could be abrogated in 1 of 2 experiments if the molecule was loaded with cholesterol before addition to culture medium. Even though culture with cholesterol-loaded MBCD increased free cholesterol content, it did not increase resistance of embryos to heat shock. Treatment of embryos with cholesterol-loaded high density lipoprotein (HDL) increased embryonic resistance to heat shock even though it slightly reduced embryo cholesterol content. It is likely that other actions of HDL (e.g., protection from free radicals) were responsible for the thermoprotective properties of this molecule. A final experiment was performed to determine whether the increased resistance of embryos at d 5 of development to heat shock as compared with the 2-cell embryo was due to changes in free cholesterol content. However, there was no significant difference in cholesterol content between 2-cell embryos and d 5 embryos that were > 16 cells in development. In conclusion, raising cholesterol content does not improve embryonic survival in response to heat shock. Depletion of cholesterol, in contrast, reduces competence of embryos to develop to the blastocyst stage. High density lipoprotein is thermoprotective to embryos and probably acts through a mechanism independent of its actions on embryonic content of free cholesterol. PMID- 22665659 TI - Relationships between transport conditions and welfare outcomes during commercial long haul transport of cattle in North America. AB - The objective of the present study was to document the relationships between selected welfare outcomes and transport conditions during commercial long haul transport of cattle (>=400 km; 6,152 journeys; 290,866 animals). Surveys were delivered to transport carriers to collect information related to welfare outcomes including the number of dead, non-ambulatory (downer) and lame animals during each journey. Transport conditions surveyed included the length of time animals spent on truck, ambient temperature, animal density, shrinkage, loading time, cattle origin, season, experience of truck drivers, and vehicle characteristics. Overall 0.012% of assessed animals became lame, 0.022% non ambulatory and 0.011% died onboard. Calves and cull cattle were more likely to die and become non-ambulatory during the journey, feeders intermediate, and fat cattle appeared to be the most able to cope with the stress of transport (P <= 0.01). The likelihood of cattle becoming non-ambulatory, lame, or dead increased sharply after animals spent over 30 h on truck (P < 0.001). The likelihood of animal death increased sharply when the midpoint ambient temperature fell below 15 degrees C (P = 0.01) while the likelihood of becoming non-ambulatory increased when temperatures rose above 30 degrees C (P = 0.03). Animals that lost 10% of their BW during transport had a greater (P < 0.001) likelihood of dying and becoming non-ambulatory or lame. Animals were more likely to die at smaller space allowances (P < 0.05), particularly at allometric coefficients below 0.015 (P = 0.10), which occurred more frequently in the belly and deck compartments of the trailers, and also at high space allowances in the deck (allometric coefficients > 0.035). The proportion of total compromised animals decreased with more years of truck driving experience (P < 0.001). Mortality was greater in cattle loaded at auction markets compared with feed yards and ranches (P < 0.01). Cull cattle, calves and feeders appear to be more affected by transport based on the likelihood of becoming non-ambulatory and dying within a journey. Most important welfare concerns during long distance transport include the total journey duration, too low or high space allowances, too high or too low ambient temperature, and the experience of the truck drivers. PMID- 22665660 TI - The environmental and economic impact of removing growth-enhancing technologies from U.S. beef production. AB - The objective of this study was to quantify the environmental and economic impact of withdrawing growth-enhancing technologies (GET) from the U.S. beef production system. A deterministic model based on the metabolism and nutrient requirements of the beef population was used to quantify resource inputs and waste outputs per 454 * 10(6) kg of beef. Two production systems were compared: one using GET (steroid implants, in-feed ionophores, in-feed hormones, and beta-adrenergic agonists) where approved by FDA at current adoption rates and the other without GET use. Both systems were modeled using characteristic management practices, population dynamics, and production data from U.S. beef systems. The economic impact and global trade and carbon implications of GET withdrawal were calculated based on feed savings. Withdrawing GET from U.S. beef production reduced productivity (growth rate and slaughter weight) and increased the population size required to produce 454 * 10(6) kg beef by 385 * 10(3) animals. Feedstuff and land use were increased by 2,830 * 10(3) t and 265 * 10(3) ha, respectively, by GET withdrawal, with 20,139 * 10(6) more liters of water being required to maintain beef production. Manure output increased by 1,799 * 10(3) t as a result of GET withdrawal, with an increase in carbon emissions of 714,515 t/454 * 10(6) kg beef. The projected increased costs of U.S. beef produced without GET resulted in the effective implementation of an 8.2% tax on beef production, leading to reduced global trade and competitiveness. To compensate for the increase in U.S. beef prices and maintain beef supply, it would be necessary to increase beef production in other global regions, with a projected increase in carbon emissions from deforestation, particularly in Brazil. Withdrawing GET from U.S. beef production would reduce both the economic and environmental sustainability of the industry. PMID- 22665661 TI - Response analysis of the Iberian pig growing from birth to 150 kg body weight to changes in protein and energy supply. AB - A total of 251 growing-finishing Iberian (IB) pigs, 32 of which were suckling piglets, were used in 5 separate sets of trials. The comparative slaughter procedure was used to determine nutrient and energy retention at several stages of growth from birth to 150 kg BW. A factorial arrangement was used within each set of trials, involving several concentrations of ideal protein in the diets as 1 factor and 2 or 3 levels of feed intake as the other. The main objective of these studies was to derive the optimal protein-to-energy ratio in the diet to allow for the expression of maximum protein deposition rates. The effect of feed restriction on growth performance, protein deposition, and fat deposition was also assessed. According to allometric equations, empty BW (EBW) was related to whole body components or total chemical constituents of empty body mass (P < 0.001). For pigs receiving solid feed, highly statistically significant multiple regression equations were constructed, which derived nutrient (g/kg) or energy (MJ/kg) composition as a function of EBW, dietary protein-to-energy ratio, and level of feeding (P < 0.001). In pigs offered adequate protein-to-energy diets, ADG at each stage of production was predicted as a function of the average BW and feeding level (P < 0.001). It was observed that the estimates of ME required for maintenance and net efficiency of utilization of ME for growth change were within rather narrow ranges throughout the growth stages studied. Preferred values (413 kJ/kg BW(0.75) * d(-1) and 0.593 for ME(m) and k(g), respectively) were obtained by regressing total energy retention (kJ/kg BW(0.75) * d(-1)) against ME intake (kJ/kg BW(0.75) * d(-1)). A multiple-regression approach revealed that in the IB pig, ME costs for protein deposition and fat deposition reach 60 and 62 kJ/g, which is considerably greater than in conventional or lean pig genotypes. In the IB pig, the maximum daily rate of protein deposition (PD(max), g) seemed to follow a linear-plateau shape with a breaking point at 32.5 kg BW, beyond which PD(max) remained at an average rate of 75 g * d(-1). The marginal efficiency of body protein deposition was estimated at each growth stage. In pigs fed on optimal or suboptimal protein-to-energy diets, the relationship between PD and ME intake declined, following a curvilinear pattern with increasing BW; thus, implying relative increases in lipid gain as BW increased. PMID- 22665662 TI - Expression of urea transporters is affected by dietary nitrogen restriction in goat kidney. AB - Ruminants are known to be able to very effectively recycle urinary urea and reuse it as a source of N for ruminal microbes. It is presumed that urea recycling is accomplished by specialized urea transporters (UT) which are localized in the kidney. This could be especially important in times of increased N requirement, such as during growth or during reduced dietary N intake. The aim of our study was to characterize and to localize UT in the goat (capra hircus) kidney and to investigate its response to reduced dietary N intake in growing goats. Therefore, 12 growing, male goats were fed either a diet containing high (17% CP in complete diet) or low (9% CP in complete diet) N content for 6 wk. After harvesting, blood and kidney samples were taken and analyzed. The mRNA of the different UT isoforms, UT-A1, UT-A2 and UT-B, were detected semiquantitatively in renal tissue by Northern blot analysis. For UT-A2 and UT-B, no statistically significant effect of dietary N restriction on renal mRNA expression could be detected (UT A2: P = 0.26, UT-B: P = 0.07). However, renal mRNA abundance of UT-A1 significantly increased in the kidney of low-N-fed goats (P = 0.01). Furthermore, protein amounts of UT-B were verified by western blotting; and the localization of UT-A2 and UT-B protein was demonstrated by immunohistochemistry. No significant differences in protein amounts of UT-B could be observed comparing the 2 feeding groups (P = 0.78). The UT-B was localized in renal medulla and papilla, whereas UT-A2 was only found in renal medulla. In addition, comparison of UT-A and UT-BAA sequences of monogastric animals and ruminants showed a high degree of homology, indicating a similar function of the transporters among these species. In summary, we conclude that in ruminants, urea reabsorption in the kidney is most likely increased in response to a low-N diet via an upregulation of UT-A1 mRNA expression. Hypothetically, the reabsorbed urea can then be returned to the rumen via the bloodstream and thus be reused as a source of N for protein synthesis of ruminal microbial community. PMID- 22665663 TI - Relationship between body condition score at calving and reproductive performance in young postpartum cows grazing native range. AB - Body condition score is used as a management tool to predict competency of reproduction in beef cows. Therefore, a retrospective study was performed to evaluate association of BCS at calving with subsequent pregnancy rate, days to first postpartum ovulation, nutrient status (assessed by blood metabolites), and calf BW change in 2- and 3-yr-old cows (n = 351) managed and selected to fit their environment of grazing native range over 6 yr at the Corona Range and Livestock Research Center, Corona, NM. Cows were managed similarly before calving, without manipulation of management, to achieve predetermined BCS at parturition. Palpable BCS (scale of 1 to 9) were determined by 2 experienced technicians before calving. Cows were classified to 1 of 3 BCS groups prior calving: BCS 4 (mean BCS = 4.3 +/- 0.02), 5 (mean BCS = 5.0 +/- 0.03), or 6 (mean BCS = 5.8 +/- 0.06). Cows were weighed weekly after calving and serum was collected once weekly (1 yr) or twice weekly (5 yr) for progesterone analysis to estimate first postpartum ovulation beginning 35 d postpartum. Year effects also were evaluated, with years identified as either above or below average precipitation. Days to first postpartum ovulation did not differ among calving BCS groups (P = 0.93). Pregnancy rates were not influenced by calving BCS (P = 0.83; 92%, 91%, 90% for BCS 4, 5, and 6, respectively). Days to BW nadir was not influenced by BCS at calving (P = 0.95). Cow BW was different at all measuring points (P < 0.01) with BCS 6 cows having the heaviest BW and cows with BCS 4 the lightest. Cows with calving BCS 4 and 5 lost more (P = 0.06) BW from the initiation of the study to the end of breeding than cows with BCS 6. However, cow BW change at all other measurement periods was not different (P >= 0.49) among calving BCS groups. Serum glucose and NEFA concentrations were not influenced by calving BCS (P >= 0.51). Calf BW at birth (P = 0.60), branding (55-d BW; P = 0.76), and weaning (205-d BW; P = 0.60) were not impacted by cow calving BCS. Body condition score did not influence overall pregnancy rates, indicating that young cows can have a reduced BCS and still be reproductively punctual. Therefore, these results indicate that reproductive performance of young cows with reduced BCS may not be affected when managed in extensive range conditions. PMID- 22665664 TI - Effects of feeding corn modified wet distillers grain plus solubles co-ensiled with direct-cut forage on feedlot performance, carcass characteristics, and diet digestibility of finishing steers. AB - Two experiments were conducted to evaluate the effects of feeding corn modified wet distillers grain plus solubles (MWDGS) co-ensiled with direct-cut forage (DC) to beef steers, on feedlot performance and total tract digestibility. In Exp. 1, sixty-four crossbred Angus steers (n = 64; 329 +/- 43 kg) were blocked by BW and randomly assigned to 1 of 4 dietary treatments: 1) corn-silage and soybean meal (CON), 2) DC co-ensiled with MWDGS (CO-EN), 3) haylage mixed with MWDGS at feeding (H+WDG), and 4) haylage mixed with dry distillers grains plus solubles at feeding (H+DDG). Steers were harvested when they reached an endpoint of 1.1 cm of 12th-rib back fat. In Exp. 2, four ruminally cannulated beef steers (initial BW = 556 +/- 31 kg) were used in a 4 * 4 Latin square to evaluate digestibility of diets used in Exp. 1. Experimental periods were 14 d in length with 10 d for diet adaptation and 4 d for sample collection. Three linear orthogonal contrasts were used to compare effects of 1) CON vs. diets containing distillers grains (DGD), 2) CO-EN vs. diets where distillers grains were mixed at feeding (MIX), and 3) H+WDG vs. H+DDG. In Exp. 1, DMI was less (P < 0.001) for steers fed CON compared with those fed DGD and greatest (P < 0.001) for steers fed CO-EN compared with MIX. Corn-silage- and soybean-meal-fed steers had more days on feed than those fed DGD (P = 0.001). Body weight gain (P = 0.02) was greater for CO-EN compared with MIX. Fat thickness at the 12th and 13th ribs was greater (P = 0.03) for DGD steers compared with CON steers. Hot carcass weight was greater (P = 0.03) for steers fed CO-EN compared with those fed MIX. Steers fed CON resulted in greater marbling scores (P = 0.01) compared DGD-fed steers. Longissimus muscle area was greater (P = 0.01) for CON-fed steers compared with all other treatments. In Exp. 2, no differences (P > 0.10) in DM, OM, or N intakes were observed. Apparent total tract DM (P = 0.01) and N (P = 0.02) digestibility were greatest in steers fed CON compared with all others. Steers fed DGD had less (P = 0.02) rumen NH(3) concentrations compared with CON. The CON diet resulted in greater molar concentrations of VFA (P = 0.03) and decreased acetate to propionate ratio (P = 0.03) compared with all DGD. These data suggest that feeding MWDGS co-ensiled with direct-cut forage results in reduced diet digestibility but equal or greater feedlot performance and similar carcass and characteristics when compared with a corn diet supplemented with soybean meal and diets where MWDGS and DDGS were added at the mixer. PMID- 22665665 TI - Barley grain-based diet treated with lactic acid and heat modulated plasma metabolites and acute phase response in dairy cows. AB - This study investigated the effects of feeding barley grain treated with lactic acid (LA) and heat on the profile of plasma metabolites related to carbohydrate and lipid metabolism and variables related to rumen health and acute phase response. Eight primiparous rumen-fistulated lactating Holstein cows were randomly assigned, in a crossover design, to 1 of the 2 dietary treatments consisting of 32% (DM basis) rolled barley grain steeped in an equal quantity of either tap water alone (CTR) or a 1.0% LA solution and heated at 55 degrees C for 48 h (LAH). Each experimental period was 21 d, with the last 10 d used for measurements. Blood samples were collected on d 1, 3, 5, 7, 9, and 11 before the morning feeding and on the last day of each period at 0, 2, 4, 6, 8, 10, and 12 h postfeeding to measure glucose, lactate, cholesterol, beta-hydroxybutyrate (BHBA), NEFA, haptoglobin (Hp), serum amyloid A (SAA), and tumor necrosis factor alpha (TNF-alpha). Also, rumen samples were collected on d 1, 5, and 11 as well as at 0, 4, 8, and 12 h postfeeding on the last day of each period for measuring the concentration of rumen endotoxin. Results of the day-to-day analysis indicated that cows fed the LAH diet had reduced preprandial concentrations of rumen endotoxin (472 vs. 793 ng/mL; P < 0.01) and cholesterol and greater lactate in the plasma; however, treatment had no effect on plasma Hp and TNF-alpha (P > 0.10). Postprandial responses showed that the LAH diet tended to decrease the concentration of SAA (4.67 vs. 8.50 MUg/mL; P = 0.06). Also, there was a treatment by time interaction for rumen endotoxin (P < 0.01), suggesting a role for both the treatment and the time of sampling on this variable. Furthermore, greater concentration of BHBA and a tendency for greater NEFA and reduced concentrations of plasma glucose were observed in cows fed the LAH diet. In conclusion, results indicated that feeding dairy cows barley grain steeped in 1.0% LA and treated with heat modulated the profile of plasma metabolites and acute phase response. PMID- 22665666 TI - Effect of dietary inulin and phytase on mineral digestibility and tissue retention in weanling and growing swine. AB - The effect of dietary phytase and the prebiotic inulin on apparent mineral digestibility, bone mineralization, and tissue mineral contents was evaluated in weanling and growing pigs. In Exp. 1, inulin and phytase were incorporated in a 2 * 3 factorial arrangement of treatments with 8 replicate pens per treatment in a randomized complete block design. There were 2 levels of phytase [0 and 1000 phytase units (FTU)/kg] and 3 levels of chicory inulin (0, 3, and 6%). Weanling pigs (17 d of age; 5 or 4 pigs per pen) with an initial BW of 6.0 +/- 0.6 kg were evaluated for 35 d postweaning. Macromineral digestibility was calculated using chromic oxide as an index in fecal samples collected during the final week of the experiment in replicates 1 through 4. On d 36, 1 pig per pen was killed and the heart, liver, kidney, and left tibia were excised and weighed. Inulin did not have any effect on growth performance measurements. Phytase increased (P < 0.05) BW on d 35 and ADG and ADFI during the 21-to-35-d and 0-to-35-d periods. Inulin did not result in increased tissue mineral concentrations on a per unit (mg/kg) or total tissue basis. Phytase increased (P < 0.05) the concentration of Zn in the liver, Mn and Zn in the heart, and Mg and Mn in the kidney. Phytase also increased (P < 0.05) total P, Mg, S, Mn, Se, and Zn in the liver as well as tibia ash. Phytase increased the digestibility of Ca (P < 0.01) and P (P < 0.05). Experiment 2 was conducted with growing pigs (initial BW, 41 +/- 5 kg) to evaluate 2 levels of inulin (0 or 6%) and 2 levels of phytase (0 or 1000 FTU/kg) in a 2 * 2 factorial with 6 replicates in a randomized complete block design. Total urine and feces were collected for 10 d from each of 24 barrows after a 21 d acclimation period. Inulin inclusion resulted in reduced Ca digestibility (P < 0.05). Phytase increased (P < 0.05) the digestibility of both Ca and P. These results indicate that dietary inulin does not affect the overall mineral status or growth performance of pigs, whereas phytase increases the utilization of Ca and several microminerals, in addition to P, and also increases growth performance. Inulin and phytase do not appear to interact to affect pig growth or mineral status. PMID- 22665667 TI - Effects of wheat or corn distillers dried grains with solubles on feedlot performance, fecal shedding, and persistence of Escherichia coli O157:H7. AB - Distillers dried grains with solubles (DDGS) are a coproduct of the ethanol industry and are often used as a replacement for grain in livestock production. Feeding corn DDGS to cattle has been linked to increased fecal shedding of Escherichia coli O157:H7, although in Canada, DDGS are often produced from wheat. This study assessed the effects of including 22.5% wheat or corn DDGS (DM basis) into barley-based diets on performance, carcass characteristics, animal health, and fecal E. coli O157:H7 shedding of commercial feedlot cattle. Cattle (n = 6,817) were randomly allocated to 10 pens per treatment group: WDDGS (diets including 22.5% wheat DDGS), CDDGS (diets including 22.5% corn DDGS), or CTRL (barley substituted for DDGS). Freshly voided fecal pats (n = 588) were collected and pooled monthly for fecal pH measurement and screened for naturally occurring E. coli O157:H7 by immunomagnetic separation (IMS) and direct plating (DP). Hide swabs (n = 367) were collected from randomly selected cattle from each pen before slaughter. Pen-floor fecal samples (n = 18) were collected from treatment groups at entry to the feedlot (<14 d on the finishing diet) and after adapting to the finishing diet for >= 14 d, inoculated (10(9) cfu of a 5 strain naldixic acid resistant E. coli O157:H7 mixture), incubated (20 degrees C) and evaluated weekly (IMS and DP) to assess fecal E. coli O157:H7 persistence. The WDDGS group had 3.0% poorer ADG (P = 0.007), 5.3% poorer G:F (P < 0.001), and a decreased proportion of Canada Quality Grade AAA carcasses (P = 0.022) compared with CTRL cattle. The CDDGS group had a similar ADG (P = 0.06), a decreased proportion of Canada Yield Grade (YG) 1 (P < 0.001), and greater proportions of Canada YG 2 (P = 0.003) and YG 3 (P < 0.001) carcasses compared with the CTRL group. There were no differences among groups in any of the animal health parameters assessed. Inclusion of DDGS in cattle finishing diets had no effect on fecal shedding (P = 0.650) or persistence (P = 0.953) of E. coli O157:H7. However, feces from cattle on starter diets <14 d had longer persistence of E. coli O157:H7 (week) than cattle on finishing diets >= 14 d (P < 0.003). Inclusion of DDGS in feedlot diets depends on commodity pricing relative to that of barley and for WDDGS must also include the risk of feedlot performance and carcass grading disadvantages. Feeding cattle barley based-diets with 22.5% corn or wheat DDGS did not affect fecal shedding of E. coli O157:H7. PMID- 22665668 TI - Effects of breed of sire on carcass composition and sensory traits of lamb. AB - This experiment was conducted to compare meat quality and carcass composition of a diverse sampling of sheep breeds. Finnsheep, Romanov, Dorper, White Dorper, Katahdin, Rambouillet, Suffolk, Texel, Dorset, and Composite (1/2 Columbia rams to 1/4; Hampshire * 1/4; Suffolk) rams were mated to mature Composite ewes. Lambs (n = 804) were reared intensively, grain finished, and serially harvested over a 63-d period. Average harvest age was 216 d and average HCW was 30.7 kg. At a common harvest age, progeny of Suffolk sires were heavier than progeny of all other breeds (P < 0.05) and their carcasses were heavier (P < 0.05) than progeny of all other breeds, except White Dorper and Dorper. Progeny of Finnsheep and Romanov sires had lighter (P < 0.05) carcasses than progeny of all other breeds. Progeny of Texel, Suffolk, White Dorper, and Dorper sires had larger (P < 0.05) LM area than all other breeds. Progeny of Finnsheep and Romanov sires had smaller (P < 0.05) LM area than all other breeds. Fat thickness at the 12th rib was greater (P < 0.05) for progeny of Dorper sires than those of all other breeds, except White Dorper and Katahdin. Fat thickness at the 4th sacral vertebrae was greater (P < 0.05) for progeny of White Dorper and Dorper sires than those of all other breeds. On a carcass weight-constant basis, progeny of Suffolk sires had a lesser (P < 0.05) percentage of ether-extractable carcass fat than progeny of all other breeds, except Texel. Regardless of harvest endpoint (age-constant or HCW constant), LM of progeny of Finnsheep and Romanov sires contained a greater (P < 0.05) percentage of intramuscular fat and received greater (P < 0.05) marbling scores than Rambouillet, Suffolk, Texel, Dorset, or Composite. Regardless of harvest endpoint, progeny of Finnsheep, Romanov, and Katahdin sires had smaller LM slice shear force values and greater trained sensory panel tenderness ratings at 7 d postmortem than did progeny of Composite, Suffolk, and Dorset sires (P < 0.05). At an age-constant basis, small differences (P < 0.05) were observed among breeds for lamb flavor intensity scores; however, when means were adjusted to a carcass weight-constant basis, breed of sire did not affect flavor intensity or off-flavor scores. These results document that each breed has relative strengths and weaknesses across traits, and that no single breed excels for all growth, carcass, and sensory traits. PMID- 22665669 TI - Loading gantry versus traditional chute for the finisher pig: effect on welfare at the time of loading and performance measures and transport losses at the harvest facility. AB - The objectives of these studies were to evaluate the loading system effects [traditional chute (TC) vs. prototype loading gantry (PLG)] on i) welfare measures at loading and ii) performance measures and transport losses at the harvest facility for the market-weight pig (Sus scrofa). This study compared first pull (FP), which was the first group of pigs, and close out (CO), which was the last group of pigs marketed from a finishing facility. Experiment 1 evaluated 74 loads for welfare measures at loading on the farm, and Exp. 2 evaluated 497 loads for performance measures and transport losses at the harvest facility. Data were analyzed using the PROC Mixed procedure for Exp. 1 and PROC GLIMMIX procedure of SAS for Exp. 2. In Exp. 1, pigs loaded using the PLG had fewer (P * 0.0002) electric prod touches, slips, falls, vocalizations, and pile ups compared with pigs loaded on the TC during FP and CO. In Exp. 2, there were no (P > 0.05) differences for any performance measures between loading systems or by pull. Pigs loaded using the prototype PLG loading gantry experienced fewer (P = 0.03) total transport losses than pigs loaded using the TC in the FP. In conclusion, the prototype loading gantry improved all welfare measures at the time of loading and reduced overall total transport losses. These studies demonstrate that loading systems that improve on-farm swine welfare at loading and reduce transport losses at the harvest facility can be designed. PMID- 22665670 TI - Sensitivity of periparturient breakdown of immunity to parasites to dietary protein source. AB - Effects of increased MP supply on the degree of periparturient relaxation of immunity (PPRI) in sheep may be dependent on quality of supplied MP. Here we tested the hypothesis that additional MP supply from rations based on xylose treated soybean meal would be more effective than from rations based on faba beans in reducing the degree of PPRI, as indicated by nematode egg excretion. Twenty-four multiple-bearing ewes were trickle infected with Teladorsagia circumcincta larvae from d -56 to d 31 relative to start of lactation (d 0). From d -26 onwards, ewes were fed at either 0.8 (LP) or at 1.2 times their respective calculated MP requirements using either xylose-treated soybean (HPS) or faba beans (HPB). Litter size was adjusted to 2 lambs at parturition. Feeding treatments did not affect nematode egg excretion, ewe BW or BCS during late pregnancy (P > 0.10), but HPS and HPB ewes had reduced plasma pepsinogen concentrations (P = 0.003). During lactation, HPS and HPB feeding increased ewe BW gain (P < 0.001) and BCS (P = 0.017), and reduced plasma pepsinogen concentrations (P = 0.008) to the same extent, compared with LP feeding. However, only HPS feeding increased litter weight gain (P = 0.017) and reduced nematode egg excretion (P = 0.015), which were both similar between HPB and LP (P > 0.10). The results support the view that extra MP supply from xylose-treated soybean based rations is more effective in reducing parasitism than MP from faba bean based rations, suggesting that protein source and/or quality are important factors to consider for the nutritional control of parasitism. PMID- 22665671 TI - Feeding 25-hydroxycholecalciferol improves gilt reproductive performance and fetal vitamin D status. AB - Little information is available regarding the effects of vitamin D and its metabolites on reproduction in swine. To investigate the effects of feeding the circulating metabolite of vitamin D, 25-hydroxycholecalciferol (25OHD3, ROVIMIX Hy * D, DSM Nutritional Products, Basel, Switzerland) on maternal and fetal circulating 25OHD3 concentration and gilt reproductive performance, a total of 40 PIC Camborough-22 gilts (BW on d -6 = 138 kg) in 4 replicates were randomly assigned to 1 of 2 corn-soybean meal-based diets. The control diet (CTL) was formulated to contain 2,500 IU D3/kg diet, and the experimental diet (25OHD3) was formulated to contain 500 IU D3/kg diet + 50 MUg 25OHD3/kg diet. Gilts were fed 2.7 kg of their assigned diet once daily beginning 43 d before breeding. Gilt BW were measured on gestational d -6 and d 90. Gilts were artificially inseminated with PIC 337-G semen 12 h and 24 h after showing signs of estrus. Blood samples were collected from the jugular vein on gestational d -43, -13, 46, and 89 for analysis of circulating 25OHD3 plasma concentration and overall vitamin D status of the gilts. At gestational d 90 +/- 1, gilts were harvested and reproductive tracts were removed. Fetal weight, sex, crown-to-rump length (CRL), as well as the number of mummified fetuses were recorded. As expected, circulating plasma concentrations of 25OHD3 were not different among treatment groups at d -43 (CTL = 53.8 ng/mL, 25OHD3 = 57.4 ng/mL; P = 0.66). However, gilts fed 25OHD3 had greater (P < 0.001) circulating plasma concentrations of 25OHD3 on d -13 (89.7 vs. 56.7 ng/mL), d 46 (95.8 vs. 55.7 ng/mL), and d 89 (92.8 vs. 58.2 ng/mL) of gestation compared with CTL-fed gilts. Circulating 25OHD3 was also greater in fetuses from 25OHD3-fed gilts on d 90 (P < 0.001). A 23% increase in pregnancy rate was observed in 25OHD3-fed gilts compared with CTL (78% vs. 55%, respectively; P = 0.21). Maternal BW gain (without conceptus), number of mummified fetuses, mean fetal weight, and mean fetal CRL were similar among treatments (P > 0.05). However, litter size was larger (CTL = 10.2; 25OHD3 = 12.7; P = 0.04) in 25OHD3-fed gilts compared with CTL-fed gilts. Notably, mean fetal weight was not decreased in 25OHD3-fed gilts as frequently occurs when litter size is increased. Overall, feeding 25OHD3 to first-service gilts before and during gestation improved both maternal and fetal vitamin D status and improved maternal reproductive performance. PMID- 22665672 TI - Immunocastration of Bos indicus x Brown Swiss bulls in feedlot with gonadotropin releasing hormone vaccine Bopriva provides improved performance and meat quality. AB - The objective of this study was to determine the effects of a GnRH vaccine on feedlot performance and meat quality in Bos indicus Zebu * Brown Swiss bulls. The study was a 2 * 2 factorial arrangement of treatments with 1,600 bulls allocated by BW into 4 groups of ~ 400 animals. The GnRH vaccine (Bopriva) was injected on d 0 and 42, and anabolic implants given on d 0 (Component E-S) and d 84 (Synovex Choice). Group designations were: Con = placebo control; Imp = implants alone; Vac = GnRH vaccine alone; and Vac+Imp = GnRH vaccine together with implants. The second GnRH vaccination at d 42 resulted in elevated titers of IgG antibody and suppressed concentrations of testosterone in vaccinated groups (Vac and Vac+Imp) at d 56 (P < 0.001), with titers and suppressed testosterone persisting to d 147 (P < 0.001). Groups Vac and Vac+Imp had reduced testes weights at slaughter on d 147 (P < 0.001). Bulls in group Vac were not different in final BW, HCW, or ADG (d 42 to 147) relative to bulls in group Con. Bulls in group Vac+Imp had greater final BW than bulls in group Imp (P = 0.008) and greater BW than bulls in group Vac and group Con (P < 0.001). The HCW of Vac+Imp bulls was greater than the Vac or Con bulls (P < 0.001) but was not different to the Imp bulls (P = 0.294). Improved ADG was obtained by vaccination with the GnRH vaccine, in the presence of implants (group Vac+Imp compared with group Imp, P < 0.001) or absence of implants (group Vac compared with group Con, P = 0.028). Meat quality of bulls receiving the GnRH vaccine was improved irrespective of implant status, with a 1.6- to 2.6-fold increase in the proportion of bulls in groups Vac and Vac+Imp, respectively, grading as USDA Choice (P < 0.002) and with greater fat depth at the 12th rib (P < 0.001). Meat tenderness was improved in the vaccine groups (Vac and Vac+Imp) compared with groups Con and Imp (P < 0.004). Use of the GnRH vaccine Bopriva in Bos indicus * Brown Swiss bulls finishing in a feedlot under Mexican husbandry conditions can provide improved performance in combination with implants (increased BW and ADG) and improved meat quality, with or without implants, and in particular, better USDA carcass grading and loin fat cover. PMID- 22665673 TI - Relationships between feed efficiency, scrotal circumference, and semen quality traits in yearling bulls. AB - A meta-analysis was conducted to examine phenotypic relationships between feed efficiency, scrotal circumference, and semen quality traits in yearling bulls. Data evaluated were obtained from 5 postweaning trials involving Angus (n = 92), Bonsmara (n = 62), and Santa Gertrudis (n = 50) bulls fed diets that ranged from 1.70 to 2.85 Mcal ME/kg DM. After an adaptation period of 24 to 28 d, feed intake was measured daily, and BW was measured at 7- or 14-d intervals during the 70- to 77-d trials. Ultrasound carcass traits (12th-rib back fat thickness, BF; LM area, LMA) and scrotal circumference (SC) were measured at the start and end of each trial. Semen samples were collected by electroejaculation within 51 d of the end of the trials when the age of bulls averaged from 365 to 444 d and were evaluated for progressive sperm motility and morphology. Residual feed intake (RFI) was calculated as the difference between actual DMI and expected DMI from linear regression of DMI on ADG and midtest BW(0.75), with trial, trial by ADG, and trial by midtest BW(0.75) as random effects. Across all studies, bulls with low RFI phenotypes (<0.5 SD below the mean RFI of 0) consumed 20% less DM and had 10% less BF but had similar ADG, SC, and semen quality traits compared with high-RFI bulls (>0.5 SD above the mean RFI of 0). Gain to feed ratio was strongly correlated with ADG (0.60) and weakly correlated with initial BW (-0.17) and DMI (-0.26). Residual feed intake was not correlated with ADG, initial age, or BW but was correlated with DMI (0.71), G:F (-0.70), and BF (0.20). Initial SC (-0.20), gain in SC (-0.28), and percent normal sperm (-0.17) were correlated with G:F, but only sperm morphology was found to be weakly associated with RFI (0.13). These data suggest that RFI is not phenotypically associated with SC or sperm motility but is weakly associated with sperm morphology. PMID- 22665674 TI - Effects of increased dietary sulfur on beef steer mineral status, performance, and meat fatty acid composition. AB - Ninety-six crossbred yearling steers (321 +/- 29 kg BW) were used to determine the effects of feeding cattle a high S diet on pasture before receiving a high S diet in the feedlot. Steers were blocked by BW, allocated to 2.4-ha bromegrass (Bromus inermis L.) pastures (n = 4 plots per treatment), and supplemented at 1% BW with either low S dried distillers grains with solubles (DDGS; 0.34% total diet S; LS) or LS DDGS with additional S (0.47% total diet S; HS) from NaSO(4) for 36 d. On d 37, steers moved into the feedlot where one-half remained on the previous S treatment and the other half switched treatments, resulting in 4 treatments (LS-LS, LS-HS, HS-LS, HS-HS; LS: 0.2 to 0.3% total diet S, HS: 0.5 to 0.6% total diet S; n = 6 feedlot pens per treatment). During the pasture period, forage mass offered, grazing residual mass, and in vitro digestible DM of forage did not differ among treatments (P > 0.40), and ADG did not differ (LS: 1.6 kg . d(-1), HS: 1.7 kg . d(-1), P = 0.54). Plasma Mg measured on d 35 was decreased by ~ 5% in response to increased dietary S during the pasture period (P = 0.05), though no effect on plasma Mg was observed during finishing (P > 0.15). Plasma Cu concentrations on d 155 were ~ 15% less (P = 0.02) in HS vs. LS steers, and d 155 liver Cu concentrations were ~ 51% less in HS vs. LS steers (P = 0.01). Increased dietary S during the feedlot period decreased ADG by ~ 10% (P = 0.01) and tended to decrease HCW by ~ 5% (P = 0.06) compared with LS steers. Steers receiving the HS diet had increased stearic acid (C18:0) and heptadecanoic acid (C17:0; P = 0.04 and 0.01, respectively) percentages in rib facings collected at slaughter. Exposing cattle to greater S diets (0.47% S) during a forage-based diet did not influence later performance on high S feedlot diets (0.5 to 0.6% S); however, cattle fed high dietary S on pasture had greater fat cover at slaughter (P = 0.01), suggesting S may have influenced lipid metabolism. PMID- 22665675 TI - Effects of saponin extracts on air emissions from steers. AB - A series of experiments were conducted to quantify the effects of saponin extracts from Quillaja saponaria Molina (QS), Yucca schidigera Roezl ex Ortgies (YS), and Camellia sinensis (L.) Kuntze (TS) on gaseous emissions from steers (Bos taurus). During Exp. 1, a control diet [C1, corn (Zea mays L.) and corn silage basal diet] was compared with YS1 (C1 + 0.64% dietary DM of YS) and QS1 (C1 + 1.5% dietary DM of QS), with 4 replicates per treatment. During Exp. 2, the control diet (C2, corn and corn silage basal diet) was compared with TS2 (C2 + 0.25% dietary DM of TS). Product inclusion levels were established to provide the same concentration of saponin compounds across studies for Exp. 1 and 2. Experiment 3 compared C3 (corn and corn silage basal diet), QS3 (C3 + 1.5% QS), YS3 (C3 + 1.5% YS), and TS3 (C3 + 0.5% TS). Holstein steers (n = 12) at initial BW of 354 +/- 10 kg (Exp. 1), 429 +/- 10 kg (Exp. 2), 382 +/- 16 kg (Period 1, Exp. 3) and 400 +/- 12 kg (Period 2, Exp. 3) were individually housed in environmental rooms for 22 d per study. Gaseous emissions including methane (CH(4)), ammonia (NH(3)), and nitrous oxide (N(2)O) were monitored in room exhaust air. No differences in DMI (7.54 +/- 0.09 kg) and ADG (1.16 +/- 0.19 kg) were observed in Exp. 1 (P > 0.05). Adding TS2 to the diet improved DMI in Exp. 2 (8.94 kg in TS2 vs. 8.53 in C2; P < 0.01), whereas ADG was not affected by diet. During Exp. 3, steers fed the TS3 diet ate less (6.36 kg/d) and gained less BW (0.31 kg/d) compared with the other 3 treatments. Saponin inclusion did not alter daily CH(4) emission per unit DMI (13.17, 10.90, and 13.21 g/kg DMI, for Exp. 1, 2, and 3, respectively). Emissions of NH(3) per unit N intake were not affected by diets in Exp. 1 (134.89 mg/g N consumed) and Exp. 3 (134.99 mg/g N consumed). Feeding TS2 reduced NH(3) emission per unit of N consumed by 30% compared with C2 (P < 0.01). Feeding up to 0.5% of TS failed to reduce CH(4) emissions without impairing steer growth. Nitrous oxide emissions were not affected by TS addition. Air emissions were not affected by feeding steers with up to 1.5% YS. Feeding 1.5% QS to steers had an inconsistent effect upon NH(3) emissions and no other effects upon gaseous emissions were seen from steers. PMID- 22665676 TI - Milk production in sows from a teat in second parity is influenced by whether it was suckled in first parity. AB - The impacts of a teat being suckled or not in first parity on its development, gene expression, and milk yield in the next parity were studied. Forty-seven first-parity sows (Sus scrofa) were divided into 2 groups: i) the same teats suckled in 2 subsequent lactations (controls, CTL; n = 22); and ii) different teats suckled in 2 subsequent lactations (treated, TRT; n = 25). In the first lactation, over half of the teats (Teats 1, 2, 5, 6, and 7 from 1 side of the udder, and Teats 3, 4, and 7 from the other side) were sealed with tape so that they were nonfunctional. During the next lactation, the CTL group had the same teats sealed as in the first lactation, whereas the opposite teats were sealed for the TRT group. In both parities, litters were standardized to 7 piglets around birth and to 6 piglets (1 piglet per available teat) at 48 h postpartum. During the second lactation, piglets were weighed at birth and on d 2, 4, 7, 14, 21, 35, and 56 postpartum. Weaning was at 17 +/- 1 d of age. Behavioral measures were obtained (using 24-h video recording) on d 3 and d 10 of lactation on 15 sows per treatment to evaluate satiety of piglets, using aggressiveness and nursing behavior as indicators. At weaning in the second lactation, 16 sows per treatment were slaughtered and 4 functional mammary glands were collected for compositional analyses and parenchyma from 2 nonfunctional glands was collected to measure mRNA abundance for selected genes. Piglets from CTL sows weighed 1.12 kg more than piglets from TRT sows (P < 0.05) on d 56, and functional mammary glands from CTL sows contained more parenchymal tissue, more DNA, and more RNA (P < 0.01) than those from TRT sows. The relative mRNA abundance of prolactin in parenchymal tissue tended to be greater in CTL than TRT sows (P < 0.10). Behavioral measures indicated a greater hunger level for piglets using teats that were not previously suckled. Current findings clearly show that teats that were suckled in first lactation produce more milk and have a greater development in the second lactation than nonsuckled teats. PMID- 22665677 TI - Effects of overfeeding naturally-mated adolescent ewes on maternal, fetal, and postnatal lamb growth. AB - The objective of this study was to evaluate the effects of overfeeding naturally mated adolescent ewes (Ovis aries) on maternal, fetal, and postnatal lamb growth, hormone concentrations, and lamb carcass characteristics. Two experiments were conducted in which singleton-bearing adolescent ewes were fed a diet containing 2.72 Mcal/kg ME at a rate which met NRC gestational age requirements (MN; n = 10 in Exp. 1, n = 7 in Exp. 2) or were fed the same diet ad libitum (15% refusal rate) throughout gestation (HN; n = 7 in Exp. 1, n = 6 in Exp. 2). Ewe BW was greater (P < 0.05) for HN than MN ewes beginning on 75 d and 52 d of gestation for Exp. 1 and 2, respectively. Final BCS was greater (P <= 0.05) for HN than MN ewes in both experiments; 3.5 vs. 3.0, respectively, for Exp. 1, and 4.8 vs. 2.9, respectively, for Exp. 2. Fasting maternal blood insulin concentrations were greater (P <= 0.05) in HN ewes near term (135 d of gestation), whereas fasting maternal glucose concentrations were greater (P <= 0.05) during most of the second half of gestation in HN ewes, for both experiments. Gestation length did not differ (P = 0.69) between treatments in Exp. 1, but in Exp. 2, HN ewes had shorter (P = 0.01) gestation lengths (144 vs. 149 d) and had increased (P = 0.002) dystocia scores. Fetal abdominal circumference was greater (P < 0.05) in lambs from MN than HN ewes at 97 d of gestation in Exp. 1 (20.8 vs. 17.4 cm) but did not differ (P = 0.94) between treatments at 95 d of gestation in Exp. 2 (averaging 20.5 cm). There were no differences (P >= 0.15) in lamb BW, abdominal circumference, crown-rump length, and biparietal distance at birth; or in postnatal BW and plasma concentrations of glucose, insulin, and lactate in either experiment. There were no differences (P >= 0.18) in HCW, dressing percentage, LM area, fat thickness, or KPH between treatments in Exp. 2. Although there was no difference (P >= 0.31) between treatments in concentrations of IGF1 or IGF2 mRNA in liver samples collected at harvest, lambs from MN ewes had greater (P <= 0.05) concentrations of IGF1R and INSR mRNA, suggesting long-term effects of maternal diet on postnatal hepatic function. In conclusion, excess nutrition during gestation in naturally-mated adolescent ewes did not affect birth weight or postnatal performance of offspring. PMID- 22665678 TI - Technical note: Mice produced by intracytoplasmic sperm injection using a modified conventional method. AB - A piezo-driven pipette that includes a small amount of mercury to enhance efficiency is widely used for mouse intracytoplasmic sperm injection (ICSI). Unfortunately, the use of toxic mercury is not permitted in hospital facilities and alternatives to mercury that enhance performance of the device do not work as well in the mouse. We have eliminated mercury toxicity and obtained acceptable ICSI efficiency using a modified conventional method. With this technique, oocyte survival, fertilization (number of 2-cell) and blastocyst rates were 77/126 (61.1%), 65/77 (84.4%), and 45/65 (69.2%), respectively. Eleven live pups were born from the transfer of thirty-two 2- to 4-cell embryos to 2 surrogate mothers. This conventional method is efficient, simple, and does not need the assistance of piezo-driven devices. PMID- 22665679 TI - One step forward for advance directives in Hong Kong. PMID- 22665680 TI - Is it feasible to discuss an advance directive with a Chinese patient with advanced malignancy? A prospective cohort study. AB - OBJECTIVES: Advance directives have been implemented for years in western countries, but the concept is new to Asian cultures. According to traditional Chinese culture, family members usually play a decisive role in a patient's treatment plan. Thus it may be hard to implement an advance directive despite its importance to the treatment of patients. The objectives of this study were to assess the feasibility of advance directive engagement and to explore significant contributing factors to achieving such a goal. DESIGN: Prospective cohort study. SETTING: Palliative Care Unit of Clinical Oncology, Tuen Mun Hospital, Hong Kong. PATIENTS: The subjects of the investigation were adult patients diagnosed to have advanced malignancy and newly referred to the hospice service from 24 April 2009 to 30 July 2009. Data were collected from nursing assessment forms, locally designed advance directive forms, a checklist completed by oncologists, and details available in the electronic hospital record. RESULTS: Of the 191 eligible patients, 120 (63%) had the advance directive, whereas 71 (37%) did not. In the Cox regression model, the patient having insight of a poor prognosis was the most significant factor facilitating advance directive engagement (P=0.001). Any family objection in the discussion of advance directives was also an important factor, though it did not reach statistical significance (P=0.082). Other factors like age, gender, education, religion, financial status, living environment, understanding the diagnosis, bereavement experience, type of cancer, nature of illness, courses of chemotherapy or radiotherapy received, main caregiver, in house supporter, nurse-led clinic attendance, clinical psychologist consultation, and in-patient hospice nurse coordinator interview were all statistically insignificant. CONCLUSIONS: Our study demonstrated that it was feasible to discuss an advance directive with Chinese patients with advanced malignancy. When patients have insight about their poor prognosis and family members have no objection, it may be appropriate to discuss an advance directive. PMID- 22665681 TI - Burnout among public doctors in Hong Kong: cross-sectional survey. AB - OBJECTIVE: The stressful life of doctors makes them prone to burnout. We evaluated the prevalence of burnout among Hong Kong public hospital doctors and correlated burnout with job characteristics, working hours, stressors, and stress relieving strategies. DESIGN: Cross-sectional survey. SETTING: Hong Kong. PARTICIPANTS: One thousand doctors were randomly sampled from the Hong Kong Public Doctors' Association registry. Self-administered, anonymous questionnaires with postage-paid envelopes were mailed twice in early 2009. The Maslach Burnout Inventory-Human Services Survey was used for burnout assessment. According to this scale, burnout is defined as emotional exhaustion, depersonalisation, and a reduced sense of personal accomplishment. Correlation analysis, as well as univariate and multivariate analyses, were performed to assess factors associated with high degrees of burnout. RESULTS. A total of 226 questionnaires were analysed, of which 31.4% of the respondents satisfied the criteria for high burnout. They were younger and needed to work shifts, and their median year of practice was 8.5. High-burnout doctors worked similar hours per week to non-high burnout doctors (mean +/- standard deviation, 56.2 +/- 12.7 vs 54.7 +/- 10.9; P=0.413) and reported suicidal thoughts more often (9.9% vs 2.6%; P=0.033). Moreover, 52.2% of high-burnout doctors were dissatisfied or very dissatisfied with their jobs. 'Excessive stress due to global workload' and 'feeling that their own work was not valued by others' were the most significant stressors associated with high emotional exhaustion and depersonalisation, while 'feeling that their own work was not valued by others' and 'poor job security' correlated with low personal accomplishment. CONCLUSIONS: A high proportion of public doctors who responded to our survey endured high burnout. Trainees with some experience were at heightened risk. Stressors identified in this study should be addressed, so as to improve job satisfaction. PMID- 22665682 TI - Primary hyperaldosteronism among Chinese hypertensive patients: how are we doing in a local district in Hong Kong. AB - OBJECTIVES: To estimate the point prevalence of primary hyperaldosteronism in a government out-patient setting and to compare associated patient characteristics with those having essential hypertension. DESIGN: Case series with external comparison. SETTING: A single public hospital (Caritas Medical Centre) and all five associated general out-patient clinics in Sham Shui Po district in Hong Kong. PATIENTS: All patients with confirmed primary hyperaldosteronism and randomly selected patients with essential hypertension from a medical specialist clinic and general out-patient clinics, retrieved from a computer database for the period January 2007 to December 2008. MAIN OUTCOME MEASURES: Estimated point prevalence of primary hyperaldosteronism among hypertensive patients treated in the public sector of Sham Shui Po district. Patient age when hypertension was diagnosed, number of antihypertensive drugs used for treatment, and the presence of target organ damage in the patients with primary hyperaldosteronism and those with essential hypertension were compared. RESULTS: Among the 46 012 patients receiving antihypertensive treatment, 49 were confirmed to have primary hyperaldosteronism. The estimated point prevalence of primary hyperaldosteronism among these hypertensive patients was 0.106% only, which was far smaller than figures from other countries. When compared with the 147 patients with essential hypertension by multivariate analysis, those with primary hyperaldosteronism were: (1) associated with longer durations of hypertension (odds ratio=1.14; 95% confidence interval, 1.06-1.24) despite being younger at the time of study, (2) likely to be taking three or more antihypertensive drugs (odds ratio=2.51; 95% confidence interval, 1.59-3.95), and (3) more likely to have left ventricular hypertrophy (odds ratio=5.01; 95% confidence interval, 1.83-13.69). All primary hyperaldosteronism patients studied presented with hypokalaemia. The need for antihypertensive drugs was markedly reduced after adrenalectomy for adrenal adenoma. CONCLUSIONS: Primary hyperaldosteronism, which is potentially a surgically curable cause of hypertension, appeared to be underdiagnosed in our locality. Screening by aldosterone-renin ratio of high-risk individuals may help improve patient outcomes. PMID- 22665683 TI - Nurse-led hypertension referral system in an emergency department for asymptomatic elevated blood pressure. AB - OBJECTIVES: To determine the characteristics of asymptomatic elevated blood pressure patients in an accident and emergency setting and assess the effect of a nurse-led intervention system. DESIGN: Cross-sectional study. SETTING: Accident and Emergency Department of a regional hospital in Hong Kong. PARTICIPANTS: Patients with blood pressures of 140/90 mm Hg or above recorded twice (at triage and discharge) with no previous history of hypertension. Exclusion criteria were: (1) admission to hospital; (2) known hypertension; (3) referral for hypertension; (4) blood pressure higher than 180/120 mm Hg on rechecking. INTERVENTION: Patients were issued a referral by the discharge nurse to follow-up for blood pressure monitoring in primary care. MAIN OUTCOME MEASURES: Diagnosis of hypertension, follow-up rate, and risk factors of hypertension. RESULTS: Of 245 patients with asymptomatic elevated blood pressure, we were able to contact 222 for follow-up, of whom 136 (61%) claimed to have been followed up for their blood pressure, and 48 (22%) were diagnosed to have hypertension. The nurse time for finding one case was 28 minutes. The projected impact could be large. If this simple nursing guideline is implemented territory-wide, more than 7000 new cases of asymptomatic hypertension might be picked up annually. CONCLUSION: The implementation of a simple nurse-led hypertension referral system is a cost effective way to screen asymptomatic subjects with elevated blood pressures in the accident and emergency department. PMID- 22665684 TI - Transcatheter ablation of atrioventricular junctional re-entrant tachycardia in children and adolescents in Hong Kong: comparison of cryothermal with radiofrequency energy. AB - OBJECTIVE: To compare the outcome of cryothermal and radiofrequency energy transcatheter ablation of atrioventricular junctional re-entrant tachycardia in children and adolescents. DESIGN: Case series with internal comparison. SETTING: Two hospitals in Hong Kong. PATIENTS: Consecutive transcatheter ablation procedures for atrioventricular junctional re-entrant tachycardia in children and adolescents in our unit from August 2000 to September 2008 were retrospectively reviewed. Radiofrequency ablation was performed from August 2000 to June 2005, and cryoablation from July 2005 to September 2008. MAIN OUTCOME MEASURES: Demographic data, outcome and procedural details. RESULTS: Thirty-eight procedures were reviewed. The radiofrequency ablation group (n=20) and cryoablation group (n=18) had similar demographic characteristics, except that there were more patients with congenital heart disease in the latter group (P=0.03). Acute procedural success rate was 100% in both groups. One patient from the radiofrequency ablation group had recurrence of atrioventricular junctional re-entrant tachycardia. The frequency of post-ablation persistent heart block was higher in the radiofrequency ablation than cryoablation group (10% vs 0%, P=0.17), but this difference was not statistically significant. A shorter fluoroscopy time was noted in the cryoablation group (31 +/- 13 vs 38 +/- 18 minutes; P=0.03). CONCLUSIONS: Transcatheter cryoablation for atrioventricular junctional re-entrant tachycardia in children and adolescents is as effective as radiofrequency ablation over the medium term. It has an excellent safety profile in terms of avoiding heart block. PMID- 22665685 TI - Quality of life in women with urinary incontinence is impaired and comparable to women with chronic diseases. AB - OBJECTIVES: To evaluate the quality of life in women with urinary incontinence (categorised by urodynamic findings). DESIGN: Prospective cohort study on patients. SETTING: Urogynaecology unit of a university teaching hospital in Hong Kong. PATIENTS. Female patients presenting to our clinic from July 2008 to December 2009 and having their urinary incontinence categorised by urodynamic study. MAIN OUTCOME MEASURES: Patient's quality of life was assessed using the Medical Outcomes Study Short Form, Urogenital Distress Inventory Short Form, and Incontinence Impact Questionnaire Short Form. Their quality of life was compared according to their urodynamic category and a subgroup analysis was performed on patients having continence surgery for urodynamic stress incontinence. RESULTS: Among the 223 women studied, 46% had urodynamic stress incontinence, 18% had detrusor overactivity, 2% had both urodynamic stress incontinence and detrusor overactivity, and 34% had no urodynamic abnormality. In all, the Medical Outcomes Study Short Form scoring was lower than normal local population. The Medical Outcomes Study Short Form score in detrusor overactivity group was significantly lower than urodynamic stress incontinence group in vitality and mental health domains. Detrusor overactivity group also had higher scores in Incontinence Impact Questionnaire Short Form in travel, social and emotional health subscales and total score (46.3 vs 29.1; P<0.01). Women with urodynamic stress incontinence and required continence surgery had higher scores in Incontinence Impact Questionnaire Short Form. CONCLUSION: Women with urinary incontinence had impaired quality of life and it was comparable to other chronic medical diseases. Women with detrusor overactivity have more impaired quality of life than women with urodynamic stress incontinence. Severity of urodynamic stress incontinence did not correlate with quality of life. Women who opted for continence surgery had poorer quality of life. PMID- 22665686 TI - Pseudoprogression of malignant glioma in Chinese patients receiving concomitant chemoradiotherapy. AB - OBJECTIVES: To investigate the frequency of pseudoprogression of glioblastoma in Chinese patients receiving concomitant chemoradiotherapy and investigate its association with pseudoprogression and tumour molecular marker O(6)-methylguanine DNA methyltransferase promoter methylation status. DESIGN: Case series with internal comparisons. SETTING: University teaching hospital, Hong Kong. PATIENTS: Patients with glioblastoma treated with concomitant chemoradiotherapy during April 2005 to June 2010 were reviewed. Magnetic resonance imaging brain scans, pre- and post-concomitant chemoradiotherapy and 3-monthly thereafter were reviewed by an independent neuroradiologist according to Macdonald's criteria. Relevant patient information (clinical condition, performance score, development of new neurological deficits, use of steroids, and survival) was retrieved. For each patient, O(6)-methylguanine-DNA methyltransferase methylation status was investigated with genomic DNA from formalin-fixed or paraffin-embedded sections of tumour tissues by methylation-specific polymerase chain reaction. RESULTS: During the study period, 28 primary glioblastoma patients underwent concomitant chemoradiotherapy. The mean age of the patients was 48 (range, 16-71) years. Thirteen patients (13/28, 46%) developed early radiological progression of the tumour after completion of concomitant chemoradiotherapy, of whom five (39%) were subsequently found to have had pseudoprogression. Patients with pseudoprogression showed a trend towards longer survival (22 months in pseudoprogression vs 17 months in all others vs 11 months in those with genuine progression). Among the 27 patients tested for O(6)-methylguanine-DNA methyltransferase promoter status, 12 (44%) were methylated. Two (2/12, 17%) in the methylated group had pseudoprogression, while three (3/15, 20%) in the unmethylated group had pseudoprogression. CONCLUSIONS: Nearly half of all patients (46%) developed early radiological progression (within 3 months of completing concomitant chemoradiotherapy). Moreover, about one in three of such patients had pseudoprogression. Pseudoprogression is an important clinical condition to be aware of to prevent premature termination of an effective treatment. PMID- 22665687 TI - Workshop 6--sources of bias in cross-sectional studies; summary on sources of bias for different study designs. PMID- 22665688 TI - Alzheimer's disease: early diagnosis and treatment. AB - With ageing of populations, the worldwide population of persons with dementia will reach over 81 million by 2040, of which the most common cause is Alzheimer's disease. In recent years, there have been major advances in the understanding of its pathogenesis, methods to diagnose it, and treatment. Magnetic resonance brain imaging, cerebrospinal fluid biomarkers, and Pittsburgh compound B and fluorodeoxyglucose positron emission tomography of the brain can facilitate an accurate diagnosis of Alzheimer's disease in its early stage, and diagnose the mild cognitive impairment stage of Alzheimer's disease. At present, only symptomatic but not disease-modifying drug treatments are available. Donepezil, rivastigmine and galantamine are the currently approved cholinesterase inhibitors for the treatment of mild, moderate, and severe Alzheimer's disease. Overall, cholinesterase inhibitors show beneficial effects on cognition, activity of daily living, behaviour, and overall clinical rating. Memantine is another symptomatic treatment for moderate-to-severe Alzheimer's disease patients. It has a small beneficial effect on cognition, activity of daily living, behaviour, and overall clinical rating. Vitamin E has antioxidant properties, and may be used in some Alzheimer's disease patients without vascular risk factors. Concurrent non pharmacological and psychosocial management of patients and their caregivers have a very important role. Disease-modifying therapies are still under development, whilst immunotherapy may be a viable option in the near future. PMID- 22665689 TI - The reference framework for diabetes care in primary care settings. AB - Diabetes has been evolving as a worldwide epidemic and constitutes one of the important global burdens of diseases. The reference framework for diabetes care has been produced by the Task Force on Conceptual Model and Preventive Protocols of the Working Group on Primary Care, so as to enhance the clinical care for diabetes patients. The guideline emphasises a comprehensive, coordinated approach with interdisciplinary collaboration between major primary care stakeholders throughout the life of the patient. It was developed by drawing on evidence from international literature with input from primary care physicians, as well as specialists including endocrinologists, doctors from public and private sectors, as well as representatives from patient groups. This article presents the latest updates on the management of diabetes, ranging from its epidemiology, patient education, prevention, early identification, complication monitoring, drug treatment, patient empowerment, and rehabilitation. It is anticipated that the adoption of this framework will contribute to better control of this chronic condition in the primary care setting. PMID- 22665690 TI - Rhabdomyolysis associated with Mycoplasma pneumoniae pneumonia. AB - We report a case of rhabdomyolysis associated with Mycoplasma pneumoniae pneumonia in a 37-year-old Sri Lankan man who presented to the emergency department with complaints of feverishness, shortness of breath, cough, and generalised muscle pain. He had a serum creatinine kinase of 14 220 U/L, serum myoglobin of 1822 ng/mL, and serum creatinine of 195 umol/L. His chest X-ray revealed bibasilar interstitial infiltrates. The antimycoplasma antibody titre was high. The patient was successfully treated with aggressive intravenous fluid replacement and azithromycin. The outcome was rapidly favourable, allowing us to discharge the patient 12 days after admission. On discharge, the serum creatinine kinase was 924 U/L and the creatinine was 126 umol/L; the chest examination was unremarkable. PMID- 22665691 TI - A sarcoma of 23 years' duration: symptom duration is not a reliable parameter to exclude malignancy. AB - This report describes a 31-year-old woman with a 23-year history of a right buttock mass that was otherwise asymptomatic, but was proven to be a low-grade fibromyxoid sarcoma (a fully malignant soft tissue tumour with a potential for distant metastasis). This case illustrates that a long-standing tumour does not necessarily imply a benign pathology. A vigilant approach should be taken for any tumours that are of significant size (larger than 5 cm). PMID- 22665692 TI - Primary spinal cord desmoplastic astrocytoma in an adolescent: a rare tumour at rare site and rare age. AB - We report a case of a non-infantile primary intramedullary spinal cord desmoplastic astrocytoma in an 18-year-old girl who presented with spastic paraparesis. The patient had been unable to run for 1 year. Magnetic resonance imaging of her spine showed an intramedullary solid and cystic heterogeneously enhancing lesion located at T7-T8 level. Partial excision was performed. Histology revealed a desmoplastic astrocytoma. To the best of our knowledge, there is no report on primary desmoplastic astrocytoma of the spinal cord in literature. Nor has such a symptomatic tumour manifesting at the age of 18 years been documented. PMID- 22665693 TI - Round ligament varicosities: a rare cause of groin swelling in pregnancy. PMID- 22665694 TI - Subtle imaging findings in a case of tight filum terminale syndrome. PMID- 22665695 TI - eHealth Record Sharing: enhancing participation for public health surveillance. PMID- 22665696 TI - Stroke at high altitude. PMID- 22665697 TI - Rational emergency stroke care in Hong Kong. PMID- 22665698 TI - Management of Dravet syndrome: emerging clinical insights. PMID- 22665699 TI - Comparison of late potentials for 24 hours between Brugada syndrome and arrhythmogenic right ventricular cardiomyopathy using a novel signal-averaging system based on Holter ECG. AB - BACKGROUND: Late potentials (LP) detected with signal-averaged ECGs are known to be useful in identifying patients at risk of Brugada syndrome (BS) and arrhythmogenic right ventricular cardiomyopathy (ARVC). Because the pathophysiology is clearly different between these disorders, we clarified the LP characteristics of these disorders. METHODS AND RESULTS: This study included 15 BS and 12 ARVC patients and 20 healthy controls. All BS patients had characteristic ECG changes and symptomatic episodes. All ARVC patients had findings that were consistent with recent criteria. Three LP parameters (filtered QRS duration, root mean square voltage of the terminal 40 ms of the filtered QRS complex, and duration of low-amplitude signals [<40 uV] in the terminal, filtered QRS complex) were continuously measured for 24 hours using a novel Holter-based signal-averaged ECG system. The incidences of LP determination in BS (80%) and ARVC (91%) patients were higher than in healthy controls (5%; P<0.0001 in both) but did not differ between BS and ARVC patients. In BS patients, the dynamic changes of all LP parameters were observed, and they were pronounced at nighttime. On the contrary, these findings were not observed in ARVC patients. When the SD values of the 3 LP parameters (filtered QRS duration, root mean square voltage of the terminal 40 ms of the filtered QRS complex, and duration of low-amplitude signals [<40 uV] in the terminal, filtered QRS complex) over 24 hours were compared for the 2 patient groups, those values in BS patients were significantly greater than those in ARVC patients (P<0.0001 in all). CONCLUSIONS: LP characteristics detected by the Holter-based signal-averaged ECG system over 24 hours differ between BS and ARVC patients. Dynamic daily variations of LPs were seen only in BS patients. This may imply that mechanisms of lethal ventricular arrhythmia in BS may be more correlated with autonomic abnormality than that of ARVC. PMID- 22665700 TI - Contributions of leaf photosynthetic capacity, leaf angle and self-shading to the maximization of net photosynthesis in Acer saccharum: a modelling assessment. AB - BACKGROUND AND AIMS: Plants are expected to maximize their net photosynthetic gains and efficiently use available resources, but the fundamental principles governing trade-offs in suites of traits related to resource-use optimization remain uncertain. This study investigated whether Acer saccharum (sugar maple) saplings could maximize their net photosynthetic gains through a combination of crown structure and foliar characteristics that let all leaves maximize their photosynthetic light-use efficiency (epsilon). METHODS: A functional-structural model, LIGNUM, was used to simulate individuals of different leaf area index (LAI(ind)) together with a genetic algorithm to find distributions of leaf angle (L(A)) and leaf photosynthetic capacity (A(max)) that maximized net carbon gain at the whole-plant level. Saplings grown in either the open or in a forest gap were simulated with A(max) either unconstrained or constrained to an upper value consistent with reported values for A(max) in A. saccharum. KEY RESULTS: It was found that total net photosynthetic gain was highest when whole-plant PPFD absorption and leaf epsilon were simultaneously maximized. Maximization of epsilon required simultaneous adjustments in L(A) and A(max) along gradients of PPFD in the plants. When A(max) was constrained to a maximum, plants growing in the open maximized their PPFD absorption but not epsilon because PPFD incident on leaves was higher than the PPFD at which epsilon(max) was attainable. Average leaf epsilon in constrained plants nonetheless improved with increasing LAI(ind) because of an increase in self-shading. CONCLUSIONS: It is concluded that there are selective pressures for plants to simultaneously maximize both PPFD absorption at the scale of the whole individual and epsilon at the scale of leaves, which requires a highly integrated response between L(A), A(max) and LAI(ind). The results also suggest that to maximize epsilon plants have evolved mechanisms that co-ordinate the L(A) and A(max) of individual leaves with PPFD availability. PMID- 22665701 TI - Classical dendritic cells as a unique immune cell lineage. AB - Despite the critical role of classical dendritic cells (cDCs) in the initiation of adaptive immune responses, the genetic and phenotypic definition of cDCs remains moot. Two new studies designate Zbtb46 as a novel transcription factor that is specifically expressed in all cDCs in both humans and mice. Although Zbtb46 appears dispensable for cDC development, its specific pattern of expression supports the notion that cDCs constitute a unique immune cell lineage. Furthermore, these two studies provide novel tools that will aid in the study of cDC progenitors, visualization of cDCs in vivo, and depletion of cDCs for functional analysis. PMID- 22665702 TI - Neural reflexes in inflammation and immunity. AB - The mammalian immune system and the nervous system coevolved under the influence of infection and sterile injury. Knowledge of homeostatic mechanisms by which the nervous system controls organ function was originally applied to the cardiovascular, gastrointestinal, musculoskeletal, and other body systems. Development of advanced neurophysiological and immunological techniques recently enabled the study of reflex neural circuits that maintain immunological homeostasis, and are essential for health in mammals. Such reflexes are evolutionarily ancient, dating back to invertebrate nematode worms that possess primitive immune and nervous systems. Failure of these reflex mechanisms in mammals contributes to nonresolving inflammation and disease. It is also possible to target these neural pathways using electrical nerve stimulators and pharmacological agents to hasten the resolution of inflammation and provide therapeutic benefit. PMID- 22665703 TI - Unstressing intemperate models: how cold stress undermines mouse modeling. AB - Mus musculus enjoys pride of place at the center of contemporary biomedical research. Despite being the current model system of choice for in vivo mechanistic analysis, mice have clear limitations. The literature is littered with examples of therapeutic approaches that showed promise in mouse models but failed in clinical trials. More generally, mice often provide poor mimics of the human diseases being modeled. Available data suggest that the cold stress to which laboratory mice are ubiquitously subjected profoundly affects mouse physiology in ways that impair the modeling of human homeostasis and disease. Experimental attention to this key, albeit largely ignored, environmental variable is likely to have a broad transformative effect on biomedical research. PMID- 22665704 TI - Frontal cortex dysfunction due to extensive hyperostosis frontalis interna. AB - An 87-year-old patient was found to have an unusually protrusive hyperostosis frontalis interna, discovered on MRI examination during an assessment of cognitive decline. Neuropsychological evaluation suggested direct repercussions of the frontal lobe compression on executive functions, as well as psychiatric disorders and possibly memory loss. PMID- 22665705 TI - Unifocal tubercular osteomyelitis of distal ulna: a rare presentation. AB - Tuberculosis is a major health issue in developing countries. The authors present a case of a 28-year-old male doctor, working as resident in the department of radiodiagnosis who attended orthopaedics outdoor with complaint of wrist pain over ulnar aspect. Radiograph of left wrist showed an oval shaped osteolytic lesion. Fine needle aspiration cytology was performed which produced only haemorrhage. Therefore, open biopsy was planned; yellowish coloured material was obtained which was sent for histopathological examination. Finally, Mycobacterium tuberculosis was isolated and thus the patient was immediately started with antitubercular therapy. This brief report emphasises upon the rare sites of skeletal tuberculosis which should always be kept in mind while diagnosing such lesions. PMID- 22665706 TI - Follicular thyroid carcinoma with pulsatile osseous metastases. PMID- 22665707 TI - A Filipino woman with autoimmune polyglandular syndrome. AB - A 47-year-old Filipino woman presented with goitre of 3 months' duration. She had no symptoms of thyrotoxicosis or hypothyroidism. Her thyroid was diffusely enlarged. Thyrotropin was elevated and free thyroxine was low. Ultrasound revealed slightly enlarged thyroid with diffuse parenchymal disease. Antithyroid peroxidase antibody was elevated. She was started on levothyroxine at 1.6 mcg/kg body weight/day and dose was adjusted to maintain the thyrotropin level within normal limits. Four years after the diagnosis of Hashimoto's thyroiditis was made, the patient started to experience malaise, generalised weakness and fatigue. Functional screening for other autoimmune endocrinopathy was done. Fasting 8 a.m serum cortisol was noted to be markedly decreased. She was diagnosed with autoimmune polyglandular syndrome type 2 (Schmidt syndrome). Physiologic dose of prednisone was started which afforded significant improvement in the patient's symptoms. The patient is on regular follow-up and clinically well. PMID- 22665708 TI - Images in paediatrics: subcutaneous fat necrosis causing radial nerve palsy. PMID- 22665709 TI - Dramatic heliotrope dermatitis and uncommon pulmonary involvement in juvenile dermatomyositis. PMID- 22665710 TI - Pancreatico-psoas fistula: a rare complication of acute pancreatitis. AB - The authors present a case of post endoscopic retrograde cholangio pancreatography acute pancreatitis complicated by a pancreatico-psoas fistula, as well as reviewing similar previously published cases. The patient had a fluctuating clinical course over 4 months, developing multiple life-threatening complications including portal vein thrombosis, gastrointestinal bleeding, aspiration pneumonia and acute kidney injury on a background of chronic kidney disease. The authors followed the long-held surgical principle of draining sepsis and avoiding surgical intervention. The fistula dried up with conservative management and time also allowed portal venous collateral formation with resolution of his ascites. PMID- 22665711 TI - Diabetes in the young but not needing insulin--what type is it? AB - A 57-year-old female who was diagnosed with diabetes at the age of 22 is presented. She was initially controlled with diet alone and then was prescribed oral glucose lowering treatment over the next 35 years. She was referred to the diabetes clinic for insulin start because of poor control of diabetes. In view of her presentation at such a young age and strong family history, a possibility of maturity onset diabetes in young was considered and the genetic test confirmed hepatocyte nuclear factor-1 alpha mutation on chromosome 12. Further oral treatment and attention to lifestyle modification improved control avoiding insulin therapy. PMID- 22665712 TI - Cryptococccal meningoencephalitis after H1N1 influenza. AB - Cryptococcus neoformans is associated with a spectrum of diseases including meningoencephalitis, pneumonia and soft tissue infections. Incidence is higher in immunocompromised hosts like HIV-infected individuals and solid organ transplant recipients. The influenza virus is known to cause immunologic defects. Additionally, the 2009-pandemic H1N1 virus is associated with increased incidence of acute respiratory distress syndrome (ARDS) requiring treatment with systemic steroids. The authors present the first case of cryptococcal meningitis in a patient with flu A-associated ARDS (FLAARDS). In this patient, risk factors for invasive fungal disease included a combination of severe and prolonged H1N1 influenza virus infection, corticosteroid therapy and broad-spectrum antibiotics. While prolonged corticosteroid use is a known risk factor for development of invasive fungal disease, the authors postulate that by causing immunologic defects and FLAARDS, the 2009-pandemic H1N1 virus may represent an additional independent risk for the development of C neoformans meningitis in a previously healthy individual. PMID- 22665713 TI - Ectopic tooth in the orbital floor: an unusual case of dentigerous cyst. PMID- 22665714 TI - Giant lipoma of the small bowel associated with perforated ileal diverticulum. AB - The authors present a rare case of the middle aged man who presented with a typical history and clinical findings suggestive of an acute appendicitis. After initial assessment, he required a surgical intervention. Operation findings revealed a perforated ileal diverticulum into a giant lipoma of the small bowel. The patient made a good postoperative recovery. PMID- 22665715 TI - Pseudohyperkalemia without reported haemolysis in a patient with chronic lymphocytic leukaemia. AB - Hyperkalemia is a medical condition that requires immediate recognition and treatment to prevent the development of life-threatening arrhythmias. Pseudohyperkalemia is most commonly due to specimen haemolysis and is often recognised by laboratory scientists who subsequently report test results with cautionary warnings. The authors present a case of pseudohyperkalemia in a patient with chronic lymphocytic leukaemia that was the result of white blood cell lysis during phlebotomy. False elevations of potassium from this condition may not be reported with a warning from the laboratory. This places the patient at risk of unnecessary and potentially dangerous treatments. This phenomenon has not been published in the emergency medicine literature to date. PMID- 22665716 TI - Anisotropic reinforcement of acute anteroapical infarcts improves pump function. AB - BACKGROUND: We hypothesize that a therapy that improves left ventricular (LV) pump function early after infarction should decrease the need for compensation through sympathetic activation and dilation, thereby reducing the risk of developing heart failure. The mechanical properties of healing myocardial infarcts are an important determinant of LV function, yet improving function by altering infarct properties has proven unexpectedly difficult. Using a computational model, we recently predicted that stiffening a large anterior infarct anisotropically (in only one direction) would improve LV function, whereas isotropic stiffening, the focus of previous studies and therapies, would not. The goal of this study was to test the novel strategy of anisotropic infarct reinforcement. METHODS AND RESULTS: We tested the effects of anisotropic infarct reinforcement in 10 open-chest dogs with large anteroapical infarcts that depressed LV pump function. We measured regional mechanics, LV volumes, and cardiac output at a range of preloads at baseline, 45 minutes after coronary ligation (ischemia), and 30 minutes later, after surgical reinforcement in the longitudinal direction (anisotropic). Ischemia shifted the end-systolic pressure volume relationship and cardiac output curves rightward, decreasing cardiac output at matched end-diastolic pressure by 44%. Anisotropic reinforcement significantly improved systolic function without impairing diastolic function, recovering half the deficit in overall LV function. CONCLUSIONS: We conclude that anisotropic reinforcement is a promising new approach to improving LV function after a large myocardial infarction. PMID- 22665717 TI - From concept to reality: a decade of progress in regional ST-elevation myocardial infarction systems. PMID- 22665719 TI - Discrete Mereotopology for Spatial Reasoning in Automated Histological Image Analysis. AB - Discrete mereotopology (DM) is a first-order spatial logic that fuses together mereology (the theory of parthood relations) and topology to model discrete space. We show how a set of quasitopological functions defined within DM can be mapped to specific operators defined in mathematical morphology (MM) and easily implemented in scientific image processing programs. These functions provide the means to model topological properties of individual regions and spatial relations between them such as contact, overlap, and the relation of part to whole. DM not only extends the expressive power of image processing applications where mathematical morphology is used, but by functioning as a logic it also supplies the formal basis with which to prove the correctness of implemented algorithms as well as providing the computational basis to mechanically reason about segmented digital images using automated reasoning programs. In particular, we show how DM can supply a model-based and algorithmic context to the otherwise blind pixel based image processing routines still dominating conventional imaging approaches. A number of worked examples drawn from the histological domain are given, including segmentation of cells in culture, identifying basal cell layers from stratified epithelia sections, and cell sorting in blood smears. PMID- 22665718 TI - Expansion of a regional ST-segment-elevation myocardial infarction system to an entire state. AB - BACKGROUND: Despite national guidelines calling for timely coronary artery reperfusion, treatment is often delayed, particularly for patients requiring interhospital transfer. METHODS AND RESULTS: One hundred nineteen North Carolina hospitals developed coordinated plans to rapidly treat patients with ST-segment elevation myocardial infarction according to presentation: walk-in, ambulance, or hospital transfer. A total of 6841 patients with ST-segment-elevation myocardial infarction (3907 directly presenting to 21 percutaneous coronary intervention hospitals, 2933 transferred from 98 non-percutaneous coronary intervention hospitals) were treated between July 2008 and December 2009 (age, 59 years; 30% women; 19% uninsured; chest pain duration, 91 minutes; shock, 9.2%). The rate of patients not receiving reperfusion fell from 5.4% to 4.0% (P=0.04). Treatment times for hospital transfer patients substantially improved. First-hospital-door to-device time for hospitals that adopted a "transfer for percutaneous coronary intervention" reperfusion strategy fell from 117 to 103 minutes (P=0.0008), whereas times at hospitals with a mixed strategy of transfer or fibrinolysis fell from 195 to 138 minutes (P=0.002). Median door-to-device times for patients presenting directly to PCI hospitals fell from 64 to 59 minutes (P<0.001). Emergency medical services-transported patients were most likely to reach door-to device goals, with 91% treated within 90 minutes and 52% being treated with 60 minutes. Patients treated within guideline goals had a mortality of 2.2% compared with 5.7% for those exceeding guideline recommendations (P<0.001). CONCLUSION: Through extension of regional coordination to an entire state, rapid diagnosis and treatment of ST-segment-elevation myocardial infarction has become an established standard of care independently of healthcare setting or geographic location. PMID- 22665720 TI - A sparse structure learning algorithm for Gaussian Bayesian Network identification from high-dimensional data. AB - Structure learning of Bayesian Networks (BNs) is an important topic in machine learning. Driven by modern applications in genetics and brain sciences, accurate and efficient learning of large-scale BN structures from high-dimensional data becomes a challenging problem. To tackle this challenge, we propose a Sparse Bayesian Network (SBN) structure learning algorithm that employs a novel formulation involving one L1-norm penalty term to impose sparsity and another penalty term to ensure that the learned BN is a Directed Acyclic Graph--a required property of BNs. Through both theoretical analysis and extensive experiments on 11 moderate and large benchmark networks with various sample sizes, we show that SBN leads to improved learning accuracy, scalability, and efficiency as compared with 10 existing popular BN learning algorithms. We apply SBN to a real-world application of brain connectivity modeling for Alzheimer's disease (AD) and reveal findings that could lead to advancements in AD research. PMID- 22665721 TI - Compressive Structured Light for Recovering Inhomogeneous Participating Media. AB - We propose a new method named compressive structured light for recovering inhomogeneous participating media. Whereas conventional structured light methods emit coded light patterns onto the surface of an opaque object to establish correspondence for triangulation, compressive structured light projects patterns into a volume of participating medium to produce images which are integral measurements of the volume density along the line of sight. For a typical participating medium encountered in the real world, the integral nature of the acquired images enables the use of compressive sensing techniques that can recover the entire volume density from only a few measurements. This makes the acquisition process more efficient and enables reconstruction of dynamic volumetric phenomena. Moreover, our method requires the projection of multiplexed coded illumination, which has the added advantage of increasing the signal-to noise ratio of the acquisition. Finally, we propose an iterative algorithm to correct for the attenuation of the participating medium during the reconstruction process. We show the effectiveness of our method with simulations as well as experiments on the volumetric recovery of multiple translucent layers, 3D point clouds etched in glass, and the dynamic process of milk drops dissolving in water. PMID- 22665722 TI - Recognition Using Specular Highlights. AB - We present a novel approach to pose estimation and model-based recognition of specular objects in difficult viewing conditions, such as low illumination, cluttered background, large highlights, and shadows that appear on the object of interest. In such challenging conditions, conventional features are unreliable. We show that under the assumption of a dominant light source, specular highlights produced by a known object can be used to establish correspondence between its image and the 3D model, and to verify the hypothesized pose and the identity of the object. Previous methods that use highlights for recognition make limiting assumptions such as known pose, scene-dependent calibration, simple shape, etc. The proposed method can efficiently recognize free-form specular objects in arbitrary pose and under unknown lighting direction. It uses only a single image of the object as its input and outputs object identity and the full pose. We have performed extensive experiments for both recognition and pose estimation accuracy on synthetic images and on real indoor and outdoor images. PMID- 22665723 TI - Energy Conservation for the Simulation of Deformable Bodies. AB - We propose a novel technique that allows one to conserve energy using the time integration scheme of one's choice. Traditionally, the time integration methods that deal with energy conservation, such as symplectic, geometric, and variational integrators, have aimed to include damping in a manner independent of the size of the time step, stating that this gives more control over the look and feel of the simulation. Generally speaking, damping adds to the overall aesthetics and appeal of a numerical simulation, especially since it damps out the high frequency oscillations that occur on the level of the discretization mesh. We propose an alternative technique that allows one to use damping as a material parameter to obtain the desired look and feel of a numerical simulation, while still exactly conserving the total energy-in stark contrast to previous methods in which adding damping effects necessarily removes energy from the mesh. This allows, for example, a deformable bouncing ball with aesthetically pleasing damping (and even undergoing collision) to collide with the ground and return to its original height exactly conserving energy, as shown in Fig. 2. Furthermore, since our method works with any time integration scheme, the user can choose their favorite time integration method with regards to aesthetics and simply apply our method as a postprocess to conserve all or as much of the energy as desired. PMID- 22665724 TI - A survey of visualization pipelines. AB - The most common abstraction used by visualization libraries and applications today is what is known as the visualization pipeline. The visualization pipeline provides a mechanism to encapsulate algorithms and then couple them together in a variety of ways. The visualization pipeline has been in existence for over 20 years, and over this time many variations and improvements have been proposed. This paper provides a literature review of the most prevalent features of visualization pipelines and some of the most recent research directions. PMID- 22665725 TI - 15-year history of spontaneous appendico-vesical fistula (case report). AB - Appendicovesical (AVF) fistula is rare complication in the modern era. Only a few cases of AVF were described in the literature of the last decade. AVF is meanly associated with a history of appendicitis. The guiding symptoms are coprosuria and pneumaturia, with recurrent infection of the urinary tract. The accurate pre operative diagnosis is difficult to make. It usually took at least one year from the onset of symptom to confirm diagnosis. It has been reported a few cases of 15 year history of undiagnosed AVF. We represent a case of EVF, spontaneously developed after treated acute appendicular colic presenting an unusual long - 15 years undiagnosed history, without presenting of typical symptoms. The analyses of disease history after cystoscopy lead to correct pre-operative diagnosis. AVF can develop as a complication not only after untreated appendicitis, but also after "successfully" treated with antibiotics appendicular colic may indicate the presence of an AVF and needs to assessing patient's history and applying cystoscopy and modern examination methods in complex diagnosis issues. PMID- 22665726 TI - The role of endogenous antiradical protective system in multiple sclerosis. AB - Present research aimed at investigation of the role of several inflammatory cytokines and free toxic radicals in Multiple Sclerosis (MS) course and disability progression as well as factors that can assist to the early transition of Relapse Remitting MS (RRMS) in Secondary Progressive MS (SPMS). Totally 22 MS patients, 14 RRMS and 8 SMPS have been investigated. Age at disease onset, disease duration, number of relapses and the Kurtzke Expanded Disability Status Scale (EDSS) scores were collected. Control comprised 10 healthy volunteers matched for age and sex. Brain was visualized by Magnetic Resonance Tomography (MRT- Siemens AVANTO-1.5-Tesla). Blood pro-inflammatory cytokines were detected by Enzyme Linked immunosorbent Assay (ELISA). Blood free toxic radicals and antioxidant enzymes were detected by Electron Paramagnetic Resonance Method (EPR). Statistics was performed using the SPSS-11.0. Blood pro- and anti inflammatory factors (gamma-Interferon, IL-6, IL-10) were elevated in MS patients against control. Increased blood IL-6 and IL-10 found in RRMS as compared to SPMS, while gamma-interferon was higher in SPMS (p<0.000). Blood EPR specters of Lypoperoxiradical (LOO-) and superoxide anion (O2-) were increased in SPMS patients compared to RRMS and control. Blood EPR specters of antioxidant enzymes: superoxidismutase (SOD), catalase (CAT) and Glutathione reductase (GR) found elevated in RRMS against SPMS and control. Positive correlation was found between gamma-interferon and EDSS (r=+0.52 p<0.05) in SPMS and negative correlation established between SOD and CAT and EDSS (r=-0.84 and r=-0.60 respectively, p<0.05) in RRMS. Multiple logistic regression toward the brain MRI Injury volume proved significance of C reactive protein, gamma-interferon and CAT. Present research suggested that the state of endogenous protection system and blood content of antioxidant enzymes (CAT, SOD) in MS patients could play a significant role for early progression of RRMS in SPMS. PMID- 22665727 TI - [Perifolliculitis capitis abscedens et suffodiens (case report)]. AB - Perifolliculitis capitis abscedens et suffodiens (PCAS) is rare chronic, suppurative and inflammatory scalp disease. Its aetiology and pathogenesis is not completely understood. The treatment is usually difficult and often disappointing. We report a case of 25-year-old male who presented with tender, fluctuant nodules and abscesses, with draining pus and patchy alopecia on his scalp for 3 years. A skin biopsy from scalp lesions revealed features that are characteristic of perifolliculitis. Initially, the patient was treated with periodic incision and drainage of the scalp abscesses. The answer was very poor. When admitted to our department, isotretinoin was started at daily dose of 30 mg, because initially his cholesterol and triglyceride levels were mildly increased. When dose was reduced to 10 mg the levels of cholesterol and triglyceride remained normal. A response to treatment was excellent and rapid. The treatment of PCAS represents usually difficulties and frustration for both the patient and the physician. A long course of isotretinoin can be considered as one of the most effective treatment for PCAS. PMID- 22665728 TI - [Neuroprotective effects of succinate-containing antihypoxante reamberine in treatment of patients with toxicohypoxic brain injury]. AB - As a result of survey in process of treatment of 60 patients with severe acute poisoning complicated by the toxic-hypoxic brain edema, found that inclusion of reamberin (antihypoxant containing succinate) in basic therapy leads to increase levels of the antioxidant defense system, decrease lipid peroxidation and reduce NR2A titers of autoantibodies. Reduction of degree of toxic-hypoxic encephalopathy promotes improving the clinical course, manifested shortened duration of coma and hospital bad days. PMID- 22665729 TI - [Pharmacological correction of hypoxia in patients with severe carbon monoxide poisoning]. AB - The article deals with the materials, which have been received in the process of the examination and treatment of 44 patients with acute severe methadone poisonings. It has been revealed, that gravity of these patients' condition depends on the intensity of hypoxia due to breath deficiency because of methadone. The development of hypoxia, in its turn, causes violations of antiradical protection system and intensification of processes of peroxide lipid oxidation. It has been registered that the including of reamberin into the complex program of the intensive therapy of acute severe methadone poisonings leads to a more rapid restoration of antiradical protection system and to a decrease of activity of processes of peroxide lipid oxidation. The correction of hypoxia and free-radical violations led to the improvement of the acute poisonings clinics, what was characterized by a decrease of coma-period duration, duration of treatment with artificial lung ventilation, a decrease of secondary lung complications and a decrease of lethality. PMID- 22665730 TI - [Comparative evaluation of clinical efficacy of drugs remaxol and ademetionine in patients with acute ethanol poisoning complicated by the toxic damage of the liver]. AB - As a result of survey in process of treatment of 100 patients with severe acute poisoning of ethanol on the background of the toxic damage of the liver set that the severity of poisoning depends on the duration abuse of alcohol (Binge drinking). Inclusion in the intensive care infusion hepatoprotector remaxol compared with ademetionine leads to a faster dynamics of improvement of the patients condition, evaluated by the scale assessing the severity APACHE II. Also found, Use of remaxol can reduce development of complications such is alcoholic delirium on the background of long-term abuse of alcohol in percentage from 31.9% to 16%, as well as reduces the time of stay of patients in the departments of the resuscitation and intensive care unit from 7,3+/-0,6 to 5,6+/-0,3 days and duration of treatment of patients in the hospital from 11,8+/-1,1 to 9,0+/-0,4 days. PMID- 22665731 TI - [Efficiency of cycloferon and reamberin combination at the treatment of the patients with chronic sepsis]. AB - The cytokine profile of blood (CPB) at the patients with chronic sepsis (CS) streptococcus or mixed (by a streptococcus and to staphylococcus etiology) was studied. To beginning of the treatment at intensifying of CS at the patients was detected the substantial increase of maintenance of proinflammatory (IL - 1beta, IL - 2, IL - 6, TNF -alpha) cytokines (CK) in the blood serum at the moderate increase of antiinflammatory CK (IL-4). Thus, indexes, characterizing correlation pro- and antiinflammatory CK was rate, that testified to predominating of proinflammatory potencies of blood. Application in the complex treatment of the patients with CS combination of modern detoxic preparation reamberin and immunoactive preparation cycloferon promotes normalizations of CK maintenance in the blood and betweennesss by them. In a clinical plan the use of the reamberin and cycloferon combination provided acceleration of CS intensifying liquidation. Finding allow to consider pathogenetic reasonable and clinically perspective application of this preparations combination in treatment of the patients with CS. PMID- 22665732 TI - International network on endocrine complications in thalassaemia (I-CET): an opportunity to grow. AB - Most of the endocrine complications in thalassaemia are attributable to iron overload which may be the result of economic circumstances (expense of the chelation therapy), late onset of chelation therapy or poor compliance with the iron chelation therapy. The major difficulties reported by hematologists or pediatric endocrinologists experienced in thalassaemias or thalassaemia syndromes in following growth disorders and endocrine complications were: lack of familiarity with medical treatment of endocrine complications (40%), interpretation of endocrine tests (30%), costs (65%), absence of paediatric endocrinologist for consultation on growth disorders and endocrine complications (27%), facilities (27%), other (e.g. lack of collaboration and on-time consultation between thalassaemic Centers supervised by hematologists and endocrinologists) (17%). Because any progress we make in research into growth disorders and endocrine complications in thalassaemia should be passed on to all those suffering from it, guaranteeing them the same therapeutic benefits and the same quality of life, on the 8th of May, 2009 in Ferrara (Italy), the International Network on Endocrine Complications in Thalassemia (I-CET) was founded. The I-CET group is planning to conduct, in Ferrara in May 2012, a workshop, "MRI and Endocrine Complications in Thalassaemia", and in Doha (Qatar) in September 2012, a 3-day intensive course entitled, "Growth disorders and Endocrine Complications in Thalassaemia", to provide interested pediatricians, physicians and hematologists from all over the world with an in-depth approach to the diagnosis and management of growth and endocrine disorders in thalassaemic patients. PMID- 22665733 TI - [Complex conservative treatment of legg-calve-perthes disease with dona- glucosamine sulfate (sachet)]. AB - The experience of 10 year application of the preparation dona - glucosamine sulphate (Sachet) Rottapharm, Italy among the children age group during the conservative treatment of thighbone head osteochondropathy (Pertes disease) at the Tbilisi, Children's Sanatorium "Gazapkhuli" orthopedic department is described in the article. In the article, it is mentioned the great importance of glicosaminglycans (GAG) in the matter of formation and existence of connective tissue, their greatest role in the metabolism of bone and cartilaginoid tissue, the considerable importance of preparation dona components (glucosamine, sulphate group) in biochemical processes that proceeds in cartilaginoid tissue - in the gialuroni acid and glicosaminglycans synthesis (the substances that the proteoglycans are composed of). The experience that the Department has in the application of polysulphate glicosaminglycan - preparation rumalon (Russia), during the conservative treatment of Pertes disease, is mentioned. Taking into account the afore-mentioned, the preparation dona was introduced into the scheme of conservative treatment of 300 child patients within 5-14 age group having different stages of Pertes disease. During 5-6 years after the treatment cessation, observation on children patients showed that during the lasting treatment period with the preparation, the hypersensitivity, negative circumstances and complications were not observed. The positive results of the treatments (90-92%), structural restoration processes both in bone and cartilaginoid tissue after the intake of roentgenologically approved preparation, gives the basis for the author of the article to express its opinion on the possibility of application of preparation dona - glucosamine sulphate (Sachet) 1500, as a structural-modified preparation, during the complex conservative treatment of Pertes disease among children within 5-14 age group. PMID- 22665734 TI - Intrafollicular pressure of colloid thyroid gland determinate the type of folliculogenesis. AB - The problem of colloid pressure of influence on the thyroid gland folliculogenesis is not clear enough in the scientific literature. The purpose of this study was to investigate the mechanism of folliculogenesis in the thyroid gland under the influence of salts of heavy metals combinations on the organism. The research was conducted on 24 white adult rats. To study the dynamics of morphological changes animals were removed from experiments on 30 and 60 days. Based on the theory of thin shells and the results of morphometric study of both groups of adult rats, which were influenced by a combination of heavy metal salts, the mathematical model to determine the level of tension in the wall of follicles was deduced. As a result of the influence of combinations of heavy metal salts on the follicular apparatus thyroid hypoactivity developed, which manifested in accumulating colloid and changing its tinctorial, physical and chemical properties, reducing the height of follicular epithelium, follicles increase in diameter, which also reflected the increasing tension in the wall of the follicle. Thus, the results allow to conclude that there is a significant role of intrafollicular colloidal pressure on the process of folliculogenesis. It is determined that in the wall of the elliptic form follicle higher tension arises in longitudinal section of the ellipse, and in cross-section the tension decreases. Analyzing the research results, we can assume that the difference between peripheral and central folliculogenesis occurs because of different amounts of intrafollicular pressure, which again are derived from different functional activity of the follicular epithelium. PMID- 22665735 TI - Antiinflammatory activity of lymphomyosot during chronic deseases. AB - Every pathology generally refers to an inadequate response to the influence brought by endo- and exotoxins, which is carried out via natural compensative and protective pathways of the body. Scientific conception of bioregulative therapy and homotoxicology implies treatment by modulation of own protective mechanisms and neutralization of already existing toxins. This endo- and exogenic homotoxins influence on the development of various immune responses of immunocompetent cells. Lymphomyosot, a complex nutural detoxifier drug, providing the effective detoxication of extracellular matrix via lymphatic system. As a huge amount of immunocompetent cells are located in the lymphatic system are, regulation of their immune responses by Lymphomyosot is very the essence of the treatment applicable to different chronic pathologies. AIM: determining of dose-dependent immunomodulating activity of Lymphomyosot on T lymphocytes modelled system of Jurkat cells. The modelled systems of Jurkat cells, incubated under moderate oxidative stress conditions inherent chronic inflammatory processes, and stimulated with mytogene Phytohemaglutinine (PHA) was used. Effectiveness of Lypmhomyosot was studied by regulatory capacity of the cells bioviability (MTT test) immunological activity (cytokine expression, respiratory burst) and of mytogene-induced apoptosis intensity of Jurkat cells. Lymphomyosot shows antioxidant effect and dose-dependent immunomodulatory activity. Lymphomyosot, as anti-inflammatory, recovering agent is effective for profilactic aims. Low (therapeutic) doses of lymphomyosot are effective for the treatment of. PMID- 22665736 TI - Characterization of oral ulcer and pathological scar in nude mice model. AB - Ulceration of mouth mucosa is frequently occurs after injuries in oral cavity. Oral ulcers are relatively common and these lesions cause strong pain and discomfort. Frequently, injury of the oral tissues results in abnormal fibroblast activation and keloid formation. This pathological scar formation is often associates with pain and malfunction of the organ. To understand these phenomena and develop effective treatment, reproducible animal models have to be introduced. Athymic nude mice where used to create animal models. 1% HCl acid solution was used for chemical damage of the mucosa tissue. Surgical operation was performed to create traumatic injury in the mouse oral cavity. Tissues were analyzed using immunohistochemistry methods. All of the HCl treated animals developed ulcers on the skin and mucosa of the oral cavity. Most of the mice on the place of surgical wound developed keloid tissue. Mice in which we induced pathological processes of the oral tissue, did not gain body weight. Moreover their mass had tendency to decrease. Hematoxilyn-eosin staining of the ulcerated mice tissues revealed extended coagulation necrosis - covering all tissue layers of the oral cavity. Strong local inflammatory cell infiltration and absence of proliferative cells has been demonstrated in these ulcerated and adjusted oral tissues. Morphological analysis of scar tissue revealed fibrotic hypertrophy of the injured oral tissues in these animals with the expressed infiltration of inflammatory cells. Our animal models reflect morphology of the specific injury and functionally imitate the disease. PMID- 22665737 TI - A survey of US dental practices' use of social media. AB - AIM: Social media is becoming the way for businesses, including health care professionals, to communicate with consumers. The study examines the use of social media by dental practices in the US. MATERIALS AND METHODS: An electronic survey was sent to 22,682 dentists in the United States. The survey consisted of questions related to the use of social media in the dental practice. Data was analyzed using descriptive statistics and comparisons were made using a Fisher's exact test. RESULTS: A total of 573 responses were received. Social media was used in 52% of dental practices, the most common being Facebook. The use of social media was most commonly for marketing purposes (91%). Dentists younger than 45 years old were more likely to use social media in their practice than dentists 45 years or older (p > 0.001). CONCLUSION: Dental practices actively use social media for marketing and communication. Many dentists are unsure how to measure the success of social media in their practice. Additional research is needed to measure the success of social media in a dental practice. CLINICAL SIGNIFICANCE: Social media is a common way practices market and interact with their patients. There are some difficulties in determining what appropriate content for social media is and how to evaluate the success. PMID- 22665738 TI - In vitro antimicrobial comparison of chlorhexidine, persica mouthwash and miswak extract. AB - AIM: Herbal mouthwashes, such as persica (Salvadora persica, mint and yarrow extracts) and miswak extract have been shown to decrease gingival inflammation and plaque accumulation. The aim of this study was to compare the antimicrobial activities of persica and miswak extract with the conventional mouthwash chlorhexidine against Streptococcus salivarius, Streptococcus sanguis, Lactobacillus vulgaris and Candida albicans. MATERIALS AND METHODS: In this in vitro study, blood-agar culture (Merk, Germany) was used to grow the streptococcus strains, saburd-dextrose culture (Merk, Germany) was used to grow C. albicans and MRS-agar was used to grow L. vulgaris. Various concentrations of these substances (0.1, 0.05 and 0.025% of miswak extract, 0.1, 0.05, 0.025 and 0.0125% of persica, 0.2, 0.1, 0.05 and 0.025% of chlorhexidine) were added to paper disks, separately, inserted into culture plates and transferred into the incubator. The inhibition zone around each disk was measured after 24 hours and the data was analyzed by the Kruskal-Wallis test. RESULTS: Chlorhexidine possessed antibacterial activity at all concentrations tested. It was more effective than persica and miswak at all concentrations on S. salivarius (p = 0.022 for 0.1%, 0.009 for 0.05 and 0.025%). It had greater effect than the other two tested material on S.sanguis only at concentration 0.01%. Chlorhexidine was the most effective against S.salivarius; persica was the most effective against Lactobacillus (p = 0.005) and the least effective against S. salivarius; and miswak extract was the most effective against S. salivarius and S. sanguis at concentrations 0.1 and 0.05% (p = 0.005) and ineffective against L. vulgaris. None of these mouthwashes were effective against C. albicans. CONCLUSION: This study revealed that chlorhexidine remains the gold standard as an antimicrobial agent, although herbal based mouthwashes do have marginal antimicrobial activities. It is necessary to conduct more clinical and microbiological studies focusing on periodontal pathogens and anaerobic microorganisms. CLINICAL SIGNIFICANCE: Mechanical plaque control is the main way for periodontal disease prevention and mouthrinses are used to improve its efficacy. Based on the results of this study, chlorhexidine has the most antibacterial effect and although persica mouthwash and miswak are routinely used in some Asian countries their antibacterial efficacies are suspected. PMID- 22665739 TI - Effect of immediate and delayed postpreparation on the integrity of the apical seal: an in vitro study. AB - AIM: The aim of this in vitro study was to evaluate if there is any significant difference in apical leakage when gutta-percha is removed immediately after obturation for postspace preparation or after a week. MATERIALS AND METHODS: Two commonly used sealers AH26 and tubliseal were used in four groups each consisting of 20 teeth each. The tooth was sectioned at the amelocemental junction to leave a root portion of 12 to 14 mm. Canals were checked for patency and prepared to No 55 K file size. Two people, using a stereomicroscope, independently evaluated each tooth-half for the extent of apical leakage. RESULTS: The leakage results were analyzed using a one-way ANOVA according to present study, immediate postpreparation is preferable than delayed postpreparation. The relationship of in vitro leakage measurements to the in vivo situation has not been established. CLINICAL IMPLICATION: Hence, immediate postpreparation is preferable than delayed postpreparation. PMID- 22665740 TI - Evaluation of subgingival microflora in diabetic and nondiabetic patients. AB - The present investigation was designed with the aim of studying the microbiota of diabetic patients-both insulin dependent and noninsulin dependent and nondiabetic individuals. Each of the three groups had 15 patients, coming under the age group of 35 to 55 years and all having periodontitis. Even though the microbial flora are almost the same, specific microorganisms may not be predisposing cause for the periodontal disease process in diabetics. The study is clinically significant by means of its implication in the treatment of bacterial infections related to periodontitis and in those patients who are having systemic diseases, like diabetes along with poor periodontal condition and infections. PMID- 22665741 TI - Salivary immunoglobulin classes in Nigerians with periodontitis. AB - AIM: To provide information on the usefulness of salivary immunoglobulin classes in the diagnosis of periodontitis. MATERIALS AND METHODS: About 5 ml of unstimulated saliva was collected from 25 newly diagnosed subjects with periodontitis and 21 sex/age-matched apparently healthy individuals into plain sample bottles. The samples were collected between 9 am and 11 am at least, 1 hour after eating or washing of mouth and levels of salivary immunoglobulin classes (IgA, IgG, IgE and IgM) were determined using enzyme-linked immunosorbent assay (ELISA). RESULTS: Only the mean level of IgA was significantly raised (p = 0.05) in the saliva of periodontitis patients compared with controls. The mean levels of IgG, IgM and IgE were not significantly elevated in patients with periodontitis, when compared with controls (p > 0.05). CONCLUSION: This study showed that elevated salivary levels of IgA could be used as a screening tool for periodontitis. CLINICAL SIGNIFICANCE: Identification of patients at risk and the diagnosis of active phases of periodontal disease remains a challenge due to lack of laboratory test routinely employed in the diagnosis and monitoring of patients with periodontal disease. This study showed that elevated salivary levels of immunoglobulin classes especially, IgA could be used as a screening tool for periodontitis. PMID- 22665742 TI - Relating the marginal fit of the castings to the accuracy of the impressions made from laminated hydrocolloid impression technique: a comparative study. AB - AIM: Relating the marginal fit of the castings, to the accuracy of the impression produced using laminated hydrocolloid impression technique, alginate and double mixed polyvinyl siloxane. Basic objective of the study is to check the feasibility of the use of laminated hydrocolloid impression technique in the fixed partial denture. MATERIALS AND METHODS: The precisely machined metal die was designed to simulate standard complete metal crown preparation. The preparation was mounted on cylindrical base of 20 mm length and diameter of 10 mm. Seven impressions were made from the each impression material onto the metal die, and total 21 impressions were obtained from all three impression materials, which were poured by the die stone, and stone die was prepared. Wax patterns were fabricated on stone dies obtained from each impression and then casting was done. All the castings were checked for the marginal fit on metal die after applying a uniform standardized load of 30 pounds using measuring microscope. RESULTS: Result revealed that the marginal fit of the castings obtained from group II (laminated hydrocolloid technique) and group III (double-mix polyvinyl polysiloxane) did not show the significant difference between the two of them. Marginal gap of the castings obtained from group I are significantly greater in comparison to the castings obtained from groups II and III (p > 0.01). CONCLUSION: Group II (laminated hydrocolloid technique) impression material may be the choice of many clinicians over group III (double-mix polyvinyl polysiloxane) impression material. Group I (alginate impression material), though very cost-effective and easy to handle may not able to produce accurate results. CLINICAL SIGNIFICANCE: The study gives overview of the best impression material that can be used clinically. Laminated hydrocolloid technique is the technique of choice. PMID- 22665743 TI - Comparison of temporomandibular disorders in Iranian dental and nondental students. AB - AIM: The aim of this study was to define the prevalence and severity of temporomandibular disorders (TMD) among Iranian dental and nondental students who attended Shiraz University of Medical Sciences. MATERIALS AND METHODS: The samples consisted of 200 subjects, 100 dental and 100 nondental students (equal distribution between males and females). Subjects ages ranged from 18 to 30 years (24.07 +/- 2.93). A functional evaluation was performed using the Helkimo dysfunction index (Di). Data were evaluated by the Chi-square test. RESULTS: Among the total study population, 71% showed some degree of dysfunction. Prevalence ratio in dental students was 80%, while in nondental students was 62% (p > 0.05, odds ratio = 0.679). With respect to gender, women (80%) were more affected than men (62%). A significant relationship was found between gender and the occurrence of TMD (p > 0.05). CONCLUSION: A high prevalence of signs of TMD in Iranian university students was seen which was greater in dental students and women. CLINICAL SIGNIFICANCE: The results of this study showed that the prevalence of TMD among dental students and women was significantly higher than nondental students and men. These findings might be due to poor postural style or emotional stress during dental practice. PMID- 22665744 TI - Symptomatic changes of oral mucosa during normal hormonal turnover in healthy young menstruating women. AB - INTRODUCTION: Changes in hormonal levels, such as those that occur during puberty, pregnancy, menstruation and menopause, have varying effects on oral cavity. Many researchers have proposed a direct link between changing hormonal status and oral health among females. OBJECTIVES: To study the various symptoms and clinical manifestations of oral cavity during normal course of menstrual cycle in healthy women. METHOD: Our study comprised of forty healthy young women volunteers with normal menstrual cycle of 28 to 30 days. A proper menstrual history was recorded from the study subjects. The entire cycle was divided into four phases comprising of bleeding, proliferative, ovulation and secretory. All the study subjects had a menstrual cycle of 28 to 30 days. Thorough recording of oral discomforts during various phases of the cycle was done during the study period. RESULTS: 30% of study subjects complained of aphthous ulcers, 5% had herpes labialis, 25% of them complained of depression, 8% showed gingival bleeding. CONCLUSION: Complaints, like oral ulcerations, mood variations, recurrent herpetic lesions, gingival bleeding in females during normal menstrual period, are attributed to the role of female sex hormones. CLINICAL SIGNIFICANCE: Lesions, like oral ulcers, recurrent herpetic lesions and increased gingival bleeding, seen in females during normal menstrual periods, could be related to hormonal turnover and therefore treated accordingly. PMID- 22665745 TI - Prevalence of dental caries and treatment needs among the orphan children and adolescents of Udaipur district, Rajasthan, India. AB - OBJECTIVE: The study was to examine the prevalence of dental caries and treatment needs among the orphan children and adolescents of Udaipur district, Rajasthan, India. METHODS: A descriptive cross-sectional study was conducted to assess the oral health status and treatment needs of orphan children. The lists obtained comprised of 13 orphanages consisting of 923 inmates including both sexes. The survey proforma was prepared using a self-administered structured questionnaire written in English validated through a pretested survey. The statistical software namely SPSS 15.0 was used for the analysis of the data. RESULTS: The prevalence of dental caries in primary teeth was found to be 49.6% and in permanent teeth was 41%. Most of the children need one surface filling followed by pulp care. CONCLUSION: The unmet needs for decayed teeth were also found to be high indicating a very poor accessibility and availability of any oral health care. Clearly, it can be concluded that this community has experienced a low utilization of preventive or therapeutic oral health services. CLINICAL SIGNIFICANCE: Orphanage children in India are usually taken care by NGOs or social workers who do not realize that dental care and oral health forms an integral part of children well-being. So, this paper enlighten the prevalence of dental caries and treatment needs among the orphan children and adolescents. PMID- 22665746 TI - Lip dimensions of an adult Nigerian population with normal occlusion. AB - INTRODUCTION: The soft tissue paradigm is placing greater emphasis on the importance of the soft tissue profile to orthodontic treatment planning. The purpose of this study was to determine the lip dimensions of a Nigerian adult population; compare the male and female values and to compare the values obtained for Nigerians with those reported for other population. METHODOLOGY: Lateral cephalometric radiographs of 100 students (44 males and 56 females) of the College of Medicine, University of Lagos, aged 18 to 25 years were taken. Selected subjects were of Nigerian ancestry with normal occlusion and a harmonious facial appearance. The radiographs were manually traced and the upper and lower lip length and thickness of each subject was measured. Statistical analysis was carried out using SPSS, while the male and female values were compared using student's t-tests. RESULTS: Mean values for the lip dimensions were computed for the entire sample. Marked sexual dimorphism was observed with the males having thicker and longer upper and lower lips than the females. The Nigerian sample also had a longer upper lip and a thicker and shorter lower lip than that reported for Caucasians. However, both population had a similar upper lip thickness. CONCLUSION: Cephalometric norms were developed for the lip dimensions of a Nigerian population. Marked sexual dimorphism was observed in the Nigerian population studied with the males having longer and thicker lips than the females. The lip dimensions of the Nigerian population studied differed from that reported for Caucasians and other racial groups. PMID- 22665747 TI - Expression of extracellular matrix-laminin in oral squamous cell carcinoma: an immunohistochemical study. AB - AIM: To evaluate the expression of laminin in various grades of oral squamous cell carcinoma (OSCC) in order to determine whether this protein can be used as a marker for early detection and elucidation of oral cancer. MATERIALS AND METHODS: Immunohistochemical staining for laminin was done on 60 selected archival blocks of histopathologically diagnosed cases of primary OSCC and the laminin expression was compared between the different histopathological grades of primary OSCC. The statistical analysis was performed by using Chi-square (X square) test and Gaussiantest with a probability of p > 0.05 was considered as significant. RESULTS: It was observed that laminin expression decreased with tumor progression which may be correlated to the tumor aggressiveness. CONCLUSION: There was a gradual decrease of laminin staining with decreasing cellular differentiation, with differentiated lesions showing a more conspicuous staining of basement membrane glycoprotein than less differentiated lesions. CLINICAL SIGNIFICANCE: An understanding of how the extracellular matrix influences tumor development and invasion is fundamental in the development of new prognostic indicators and treatment strategies for oral squamous cell carcinoma.. PMID- 22665748 TI - Dental plaque pH variation with regular soft drink, diet soft drink and high energy drink: an in vivo study. AB - BACKGROUND: A high incidence of dental caries and dental erosion associated with frequent consumption of soft drinks has been reported. The purpose of this study was to evaluate the pH response of dental plaque to a regular, diet and high energy drink. METHODOLOGY: Twenty subjects were recruited for this study. All subjects were between the ages of 20 and 25 and had at least four restored tooth surfaces present. The subjects were asked to refrain from brushing for 48 hours prior to the study. At baseline, plaque pH was measured from four separate locations using harvesting method. Subjects were asked to swish with 15 ml of the respective soft drink for 1 minute. Plaque pH was measured at the four designated tooth sites at 5, 10 and 20 minutes intervals. Subjects then repeated the experiment using the other two soft drinks. RESULTS: pH was minimum for regular soft drink (2.65 +/- 0.026) followed by high energy drink (3.39 +/- 0.026) and diet soft drink (3.78 +/- 0.006). The maximum drop in plaque pH was seen with regular soft drink followed by high energy drink and diet soft drink. CONCLUSION: Regular soft drink possesses a greater acid challenge potential on enamel than diet and high energy soft drinks. However, in this clinical trial, the pH associated with either soft drink did not reach the critical pH which is expected for enamel demineralization and dissolution. PMID- 22665749 TI - Comparison of COX2 expression between oral squamous cell carcinoma, leukoplakia and normal mucosa. AB - AIM: To compare cyclooxygenase 2 expression (COX2-E) between normal, oral leukoplakia lesions and different grades of oral squamous cell carcinoma (SCC). MATERIALS AND METHODS: Around 90 paraffin embedded blocks consisting of 45 SCC, 15 leukoplakia and 17 controls were selected for immunohistochemistry (IHC) for detection of COX2- E. COX2-E was divided in four grades, as A (0-10%), B (11- 40%), C (41-70%) and D (< 70%) cellularity. RESULTS: Mean age of the patients was 55.17 +/- 18.41 (M:57.92 +/- 16.87, F:52.19 +/- 19.74). A significant difference was found in COX2 expression between SCC total and, basal and spinous layers of leukoplakia (p > 0.05). COX2-E in spinous layer of normal tissue was significantly lower than SCC (p = 0.000). COX2-E was significantly different in SCC grade 3 and leukoplakia (p = 0.001) and normal tissue (p = 0.000). COX2-E was significantly higher in SCC grade 3 compared to leukoplakia (basal layer) (p = 0.000). CONCLUSION: We showed a significant higher COX2-E in SCC lesions compared to leukoplakias and normal controls. In our study COX2-E was not significantly different in SCC grades 1, 2 and 3 (p < 0.05). PMID- 22665750 TI - Fracture strength of three all-ceramic systems: Top-Ceram compared with IPS Empress and In-Ceram. AB - PURPOSE: The purpose of this study was to investigate the fracture loads and mode of failure of all-ceramic crowns fabricated using Top-Ceram and compare it with all-ceramic crowns fabricated from well-established systems: IPS-Empress II, In Ceram. MATERIALS AND METHODS: Thirty all-ceramic crowns were fabricated; 10 IPS Empress II, 10 In-Ceram alumina and 10 Top-Ceram. Instron testing machine was used to measure the loads required to introduce fracture of each crown. RESULTS: Mean fracture load for In-Ceram alumina [941.8 (+/- 221.66) N] was significantly (p > 0.05) higher than those of Top-Ceram and IPS-Empress II. There was no statistically significant difference between Top-Ceram and IPS-Empress II mean fracture loads; 696.20 (+222.20) and 534 (+110.84) N respectively. Core fracture pattern was highest seen in Top- Ceram specimens. PMID- 22665751 TI - Dentures with phonetically contoured palate: a simple technique of adding customized rugae and palatal contours to the maxillary denture. AB - Speech is essential to human activity, therefore phonetics must be considered with mechanics and esthetics as the cardinal factors contributing to the success of the dental prosthesis. The aim of this following procedure is to produce dentures that are mechanically functional, esthetically pleasing and permit normal speech. PMID- 22665752 TI - A nonsurgical technique for the removal of overextended gutta-percha. AB - AIM: The present report describes and discusses a nonsurgical technique for the removal of overextended gutta-percha. BACKGROUND: Mechanical irritation results from overextension and the overextended material used during root canal obturation could produce an inflammatory reaction with an area of rarefaction in the periapical tissues. The healing process is not affected by the presence of filling materials as it is well tolerate by the periapical tissues, but it is accepted that a higher failure rate is found in overfilled teeth. CASE REPORT: This clinical report describes one case with an overextended gutta-percha cone and a new nonsurgical technique to remove this material. CONCLUSION: The technique described is a conservative, safe and plausible option to remove extruded gutta-percha in periapical area. CLINICAL SIGNIFICANCE: Overextended gutta-percha cones could increase the failure of endodontic therapy. Commonly surgical procedures are indicated to remove this overextended material, but this nonsurgical technique could be a better treatment alternative and could increase the chances of success. PMID- 22665753 TI - Recording 'sublingual crescents' in lower complete dentures: a technique so effective but still esoteric and arcane. AB - AIM: To achieve retention in severely resorbed mandibular ridges during impression making and to maintain the retention and stability of these dentures during function. BACKGROUND: No good method with adequate clinical photographs that will empower the dentist with the necessary skill has been reported in the literature. TECHNIQUE: The technique involves making a preliminary impression in alginate to record the denture bearing area clearly, doing a border moulding procedure with excess width to fill the wide sulcus present; except in the area of anterior lingual flange from second premolar to second premolar area. The anterior lingual border of the impression is then extended sublingually without interfering with the tongue function or blocking the opening of the ducts of the sublingual gland; to maintain contact with the surrounding sublingual tissue in both protruded and retruded positions of the tongue, thereby creating good peripheral seal in the most vulnerable area in the lower denture, where the seal is easily broken during tongue movements. CONCLUSION: This impression technique, combined with arrangement of teeth on the center of the ridge in the posterior part, use of flattened cusp posterior teeth and contoured polish surface of denture base (Fisch concept) provide sufficient retention and stability to the dentures made on these severely resorbed ridges. CLINICAL SIGNIFICANCE: Patients with severely resorbed ridges cannot be rehabilitated with implants also and so normally suffer with loose lower denture fabricated with normal border moulding procedures. These patients can be rehabilitated to a great extent properly. PMID- 22665754 TI - Oral rehabilitation of a patient with amelogenesis imperfecta using removable overlay denture: a clinical report. AB - AIM: The aim of this study was oral rehabilitation of 17-year old patient with amelogenesis imperfecta using removable overlay denture in order to satisfy her esthetic and functional expectations and enhance her self-image. BACKGROUND: Amelogenesis imperfecta (AI) is a group of genetic disorders that primarily affect the quality and quantity of amelogenesis in both primary and permanent dentitions. The main clinical characteristics are severe attrition, tooth sensitivity and unesthetic appearance. CASE REPORT: This clinical report illustrates the oral rehabilitation of a 17-year-old girl with hypoplastic hypomature type of AI with cobalt-chromium (Co-Cr) overlay removable partial denture (ORPD) that is one of the most economical and biocompatible replacements for noble metal and nickel-chromium (Ni-Cr) alloy. CONCLUSION: The presented case report suggests that Co-Cr ORPD can be a good temporary or even permanent treatment option for AI patients with limited budget, low esthetic concerns or medical limitations. CLINICAL SIGNIFICANCE: There are major advantages in cast metal ORPDs; they are simpler, less traumatic and less expensive than fixed prosthetic options. This case report supports their use in patients with amelogenesis imperfecta. PMID- 22665755 TI - Orbital trauma: keep an eye for the details! AB - Orbital injuries are often missed out when they occur concomitantly with other facial bone fractures. Clinical examination and plain radiographic findings alone may prove inadequate in the detection of orbital floor fractures. Refined imaging techniques like CT scans and MRI are immensely helpful in the diagnosis of orbital blowout fractures. A case of 'impure' orbital blowout fracture which went undetected at the time of initial examination and its secondary surgical reconstruction is reported here. This case report emphasizes the importance of careful clinical and radiologic evaluation in orbital injuries. PMID- 22665756 TI - A starter's guide to preclinical teeth arrangement: simplified clinometer. AB - Arrangement of artificial teeth in a bilaterally symmetrical fashion with proper inclinations of teeth had been a challenging task for beginners. A variety of tools and guiding equipment have been developed to help students to learn teeth arrangement. Unfortunately, those tools were either costly or unsuitable for use with mean value articulators. This article attempts to introduce a simplified clinometer which can be attached to mean value articulator and can be used as a guide to arrange teeth in a bilaterally symmetrical manner by the undergraduates in both clinical and preclinical set-up. CLINICAL SIGNIFICANCE: Training of the future dentists in sound esthetic principles in a preclinical environment, using this device, will increase the final clinical efficacy of their work. AIM: The aim of this article is to provide a simple but effective device to undergraduate students to help them learn teeth arrangement easily and systematically. PMID- 22665757 TI - Saliva: a powerful diagnostic tool for minimal intervention dentistry. AB - Saliva plays a vital role in oral health as patients strive to maintain a healthy dentition throughout their lives. It is natures primary defense mechanism for the oral environment, and is particularly important for protecting exposed tooth surfaces. While internal protection for dentin comes from odontoblasts and the dental pulp, the body's external protection for enamel comes from saliva. The noninvasive nature of salivary testing has made it an effective alternative to blood and urine testing and home testing kits have made it possible for people to monitor their own health using this diagnostic medium. This paper presents what saliva can reveal about general and oral health as well as highlights the current use and potential clinical and research applications, of diagnostics based on oral fluids. CLINICAL SIGNIFICANCE: Early detection always minimizes the need for more invasive treatment. It prevents oral health disease at an early stage and provides a good oral health in rejuvenated state. If you stick and follow regular professional care, prevention maintenance appointments, prevention counseling, good home care and oral hygiene, diet habits you will be free from oral health illness and you can experience the harmonious and rejuvenated state of good oral health. PMID- 22665758 TI - Behavior shaping of complete denture patient: a theoretical approach. AB - The psychological status of a geriatric patient undergoing complete denture treatment is one of the key determinants of the success of prosthesis. Hence, the understanding and behavior management of such patients is of paramount importance for any clinician aspiring to be a successful in practice. Even though several attempts have been made to understand the effects of psychology of patients undergoing this particular treatment on the final outcome of treatment, no single theory or classification has been proposed so far as to be able to completely understand the thought process of geriatric patients. The aim of this paper is to propose a theoretical approach, a step by step guide to clinicians to better understand the thoughts, aspirations and expectations of complete denture patients and their effects and consequences in different patients, when not met with. PMID- 22665759 TI - Occlusion revisited. AB - The evaluation of occlusion is of utmost importance, when planning for dental and orthodontic treatment. The occlusal characteristics of normal occlusion change according to the dentoalveolar maturation stages. In primary dentition, flush terminal plane relationship of the second primary molars is desired for a normal molar relationship. In the early mixed dentition stage, cusp to cusp molar relationship is the normal occlusal feature, when posterior primary teeth are in place and leeway space is preserved. PMID- 22665760 TI - Root canal obturation update: where do we stand today? PMID- 22665761 TI - Wet-surface-enhanced ellipsometric contrast microscopy identifies slime as a major adhesion factor during bacterial surface motility. AB - In biology, the extracellular matrix (ECM) promotes both cell adhesion and specific recognition, which is essential for central developmental processes in both eukaryotes and prokaryotes. However, live studies of the dynamic interactions between cells and the ECM, for example during motility, have been greatly impaired by imaging limitations: mostly the ability to observe the ECM at high resolution in absence of specific staining by live microscopy. To solve this problem, we developed a unique technique, wet-surface enhanced ellipsometry contrast (Wet-SEEC), which magnifies the contrast of transparent organic materials deposited on a substrate (called Wet-surf) with exquisite sensitivity. We show that Wet-SEEC allows both the observation of unprocessed nanofilms as low as 0.2 nm thick and their accurate 3D topographic reconstructions, directly by standard light microscopy. We next used Wet-SEEC to image slime secretion, a poorly defined property of many prokaryotic and eukaryotic organisms that move across solid surfaces in absence of obvious extracellular appendages (gliding). Using combined Wet-SEEC and fluorescent-staining experiments, we observed slime deposition by gliding Myxococcus xanthus cells at unprecedented resolution. Altogether, the results revealed that in this bacterium, slime associates preferentially with the outermost components of the motility machinery and promotes its adhesion to the substrate on the ventral side of the cell. Strikingly, analogous roles have been proposed for the extracellular proteoglycans of gliding diatoms and apicomplexa, suggesting that slime deposition is a general means for gliding organisms to adhere and move over surfaces. PMID- 22665762 TI - Environmental and biotic controls on the evolutionary history of insect body size. AB - Giant insects, with wingspans as large as 70 cm, ruled the Carboniferous and Permian skies. Gigantism has been linked to hyperoxic conditions because oxygen concentration is a key physiological control on body size, particularly in groups like flying insects that have high metabolic oxygen demands. Here we show, using a dataset of more than 10,500 fossil insect wing lengths, that size tracked atmospheric oxygen concentrations only for the first 150 Myr of insect evolution. The data are best explained by a model relating maximum size to atmospheric environmental oxygen concentration (pO(2)) until the end of the Jurassic, and then at constant sizes, independent of oxygen fluctuations, during the Cretaceous and, at a smaller size, the Cenozoic. Maximum insect size decreased even as atmospheric pO(2) rose in the Early Cretaceous following the evolution and radiation of early birds, particularly as birds acquired adaptations that allowed more agile flight. A further decrease in maximum size during the Cenozoic may relate to the evolution of bats, the Cretaceous mass extinction, or further specialization of flying birds. The decoupling of insect size and atmospheric pO(2) coincident with the radiation of birds suggests that biotic interactions, such as predation and competition, superseded oxygen as the most important constraint on maximum body size of the largest insects. PMID- 22665763 TI - Gaucher disease gene GBA functions in immune regulation. AB - Inherited deficiency of acid beta-glucosidase (GCase) due to biallelic mutations in the GBA (glucosidase, beta, acid) gene causes the classic manifestations of Gaucher disease (GD) involving the viscera, the skeleton, and the lungs. Clinical observations point to immune defects in GD beyond the accumulation of activated macrophages engorged with lysosomal glucosylceramide. Here, we show a plethora of immune cell aberrations in mice in which the GBA gene is deleted conditionally in hematopoietic stem cells (HSCs). The thymus exhibited the earliest and most striking alterations reminiscent of impaired T-cell maturation, aberrant B-cell recruitment, enhanced antigen presentation, and impaired egress of mature thymocytes. These changes correlated strongly with disease severity. In contrast to the profound defects in the thymus, there were only limited cellular defects in peripheral lymphoid organs, mainly restricted to mice with severe disease. The cellular changes in GCase deficiency were accompanied by elevated T-helper (Th)1 and Th2 cytokines that also tracked with disease severity. Finally, the proliferation of GCase-deficient HSCs was inhibited significantly by both GL1 and Lyso-GL1, suggesting that the "supply" of early thymic progenitors from bone marrow may, in fact, be reduced in GBA deficiency. The results not only point to a fundamental role for GBA in immune regulation but also suggest that GBA mutations in GD may cause widespread immune dysregulation through the accumulation of substrates. PMID- 22665764 TI - Reciprocal uniparental disomy in yeast. AB - In the diploid cells of most organisms, including humans, each chromosome is usually distinguishable from its partner homolog by multiple single-nucleotide polymorphisms. One common type of genetic alteration observed in tumor cells is uniparental disomy (UPD), in which a pair of homologous chromosomes are derived from a single parent, resulting in loss of heterozygosity for all single nucleotide polymorphisms while maintaining diploidy. Somatic UPD events are usually explained as reflecting two consecutive nondisjunction events. Here we report a previously undescribed mode of chromosome segregation in Saccharomyces cerevisiae in which one cell division produces daughter cells with reciprocal UPD for the same pair of chromosomes without an aneuploid intermediate. One pair of sister chromatids is segregated into one daughter cell and the other pair is segregated into the other daughter cell, mimicking a meiotic chromosome segregation pattern. We term this process "reciprocal uniparental disomy." PMID- 22665765 TI - Casparian strip diffusion barrier in Arabidopsis is made of a lignin polymer without suberin. AB - Casparian strips are ring-like cell-wall modifications in the root endodermis of vascular plants. Their presence generates a paracellular barrier, analogous to animal tight junctions, that is thought to be crucial for selective nutrient uptake, exclusion of pathogens, and many other processes. Despite their importance, the chemical nature of Casparian strips has remained a matter of debate, confounding further molecular analysis. Suberin, lignin, lignin-like polymers, or both, have been claimed to make up Casparian strips. Here we show that, in Arabidopsis, suberin is produced much too late to take part in Casparian strip formation. In addition, we have generated plants devoid of any detectable suberin, which still establish functional Casparian strips. In contrast, manipulating lignin biosynthesis abrogates Casparian strip formation. Finally, monolignol feeding and lignin-specific chemical analysis indicates the presence of archetypal lignin in Casparian strips. Our findings establish the chemical nature of the primary root-diffusion barrier in Arabidopsis and enable a mechanistic dissection of the formation of Casparian strips, which are an independent way of generating tight junctions in eukaryotes. PMID- 22665766 TI - Plant tropane alkaloid biosynthesis evolved independently in the Solanaceae and Erythroxylaceae. AB - The pharmacologically important tropane alkaloids have a scattered distribution among angiosperm families, like many other groups of secondary metabolites. To determine whether tropane alkaloids have evolved repeatedly in different lineages or arise from an ancestral pathway that has been lost in most lines, we investigated the tropinone-reduction step of their biosynthesis. In species of the Solanaceae, which produce compounds such as atropine and scopolamine, this reaction is known to be catalyzed by enzymes of the short-chain dehydrogenase/reductase family. However, in Erythroxylum coca (Erythroxylaceae), which accumulates cocaine and other tropane alkaloids, no proteins of the short chain dehydrogenase/reductase family were found that could catalyze this reaction. Instead, purification of E. coca tropinone-reduction activity and cloning of the corresponding gene revealed that a protein of the aldo-keto reductase family carries out this reaction in E. coca. This protein, designated methylecgonone reductase, converts methylecgonone to methylecgonine, the penultimate step in cocaine biosynthesis. The protein has highest sequence similarity to other aldo-keto reductases, such as chalcone reductase, an enzyme of flavonoid biosynthesis, and codeinone reductase, an enzyme of morphine alkaloid biosynthesis. Methylecgonone reductase reduces methylecgonone (2 carbomethoxy-3-tropinone) stereospecifically to 2-carbomethoxy-3beta-tropine (methylecgonine), and has its highest activity, protein level, and gene transcript level in young, expanding leaves of E. coca. This enzyme is not found at all in root tissues, which are the site of tropane alkaloid biosynthesis in the Solanaceae. This evidence supports the theory that the ability to produce tropane alkaloids has arisen more than once during the evolution of the angiosperms. PMID- 22665767 TI - Direct reciprocity in structured populations. AB - Reciprocity and repeated games have been at the center of attention when studying the evolution of human cooperation. Direct reciprocity is considered to be a powerful mechanism for the evolution of cooperation, and it is generally assumed that it can lead to high levels of cooperation. Here we explore an open-ended, infinite strategy space, where every strategy that can be encoded by a finite state automaton is a possible mutant. Surprisingly, we find that direct reciprocity alone does not lead to high levels of cooperation. Instead we observe perpetual oscillations between cooperation and defection, with defection being substantially more frequent than cooperation. The reason for this is that "indirect invasions" remove equilibrium strategies: every strategy has neutral mutants, which in turn can be invaded by other strategies. However, reciprocity is not the only way to promote cooperation. Another mechanism for the evolution of cooperation, which has received as much attention, is assortment because of population structure. Here we develop a theory that allows us to study the synergistic interaction between direct reciprocity and assortment. This framework is particularly well suited for understanding human interactions, which are typically repeated and occur in relatively fluid but not unstructured populations. We show that if repeated games are combined with only a small amount of assortment, then natural selection favors the behavior typically observed among humans: high levels of cooperation implemented using conditional strategies. PMID- 22665768 TI - Temporal expression of microRNA cluster miR-17-92 regulates effector and memory CD8+ T-cell differentiation. AB - MicroRNAs are important regulators of various developmental and physiological processes. However, their roles in the CD8(+) T-cell response are not well understood. Using an acute viral infection model, we show that microRNAs of the miR-17-92 cluster are strongly induced after T-cell activation, down-regulated after clonal expansion, and further silenced during memory development. miR-17-92 promotes cell-cycle progression of effector CD8(+) T cells, and its expression is critical to the rapid expansion of these cells. However, excessive miR-17-92 expression enhances mammalian target of rapamycin (mTOR) signaling and strongly skews the differentiation toward short-lived terminal effector cells. Failure to down-regulate miR-17-92 leads to a gradual loss of memory cells and defective central memory cell development. Therefore, our results reveal a temporal expression pattern of miR-17-92 by antigen-specific CD8(+) T cells during viral infection, the precise control of which is critical to the effector expansion and memory differentiation of CD8(+) T cells. PMID- 22665769 TI - Pathogenesis of emerging severe fever with thrombocytopenia syndrome virus in C57/BL6 mouse model. AB - The discovery of an emerging viral disease, severe fever with thrombocytopenia syndrome (SFTS), caused by SFTS virus (SFTSV), has prompted the need to understand pathogenesis of SFTSV. We are unique in establishing an infectious model of SFTS in C57/BL6 mice, resulting in hallmark symptoms of thrombocytopenia and leukocytopenia. Viral RNA and histopathological changes were identified in the spleen, liver, and kidney. However, viral replication was only found in the spleen, which suggested the spleen to be the principle target organ of SFTSV. Moreover, the number of macrophages and platelets were largely increased in the spleen, and SFTSV colocalized with platelets in cytoplasm of macrophages in the red pulp of the spleen. In vitro cellular assays further revealed that SFTSV adhered to mouse platelets and facilitated the phagocytosis of platelets by mouse primary macrophages, which in combination with in vivo findings, suggests that SFTSV-induced thrombocytopenia is caused by clearance of circulating virus-bound platelets by splenic macrophages. Thus, this study has elucidated the pathogenic mechanisms of thrombocytopenia in a mouse model resembling human SFTS disease. PMID- 22665770 TI - Multiscale natural moves refine macromolecules using single-particle electron microscopy projection images. AB - The method presented here refines molecular conformations directly against projections of single particles measured by electron microscopy. By optimizing the orientation of the projection at the same time as the conformation, the method is well-suited to two-dimensional class averages from cryoelectron microscopy. Such direct use of two-dimensional images circumvents the need for a three-dimensional density map, which may be difficult to reconstruct from projections due to structural heterogeneity or preferred orientations of the sample on the grid. Our refinement protocol exploits Natural Move Monte Carlo to model a macromolecule as a small number of segments connected by flexible loops, on multiple scales. After tests on artificial data from lysozyme, we applied the method to the Methonococcus maripaludis chaperonin. We successfully refined its conformation from a closed-state initial model to an open-state final model using just one class-averaged projection. We also used Natural Moves to iteratively refine against heterogeneous projection images of Methonococcus maripaludis chaperonin in a mix of open and closed states. Our results suggest a general method for electron microscopy refinement specially suited to macromolecules with significant conformational flexibility. The algorithm is available in the program Methodologies for Optimization and Sampling In Computational Studies. PMID- 22665771 TI - Digital atom interferometer with single particle control on a discretized space time geometry. AB - Engineering quantum particle systems, such as quantum simulators and quantum cellular automata, relies on full coherent control of quantum paths at the single particle level. Here we present an atom interferometer operating with single trapped atoms, where single particle wave packets are controlled through spin dependent potentials. The interferometer is constructed from a sequence of discrete operations based on a set of elementary building blocks, which permit composing arbitrary interferometer geometries in a digital manner. We use this modularity to devise a space-time analogue of the well-known spin echo technique, yielding insight into decoherence mechanisms. We also demonstrate mesoscopic delocalization of single atoms with a separation-to-localization ratio exceeding 500; this result suggests their utilization beyond quantum logic applications as nano-resolution quantum probes in precision measurements, being able to measure potential gradients with precision 5 x 10(-4) in units of gravitational acceleration g. PMID- 22665772 TI - Effect of mass transfer on the oxygen reduction reaction catalyzed by platinum dendrimer encapsulated nanoparticles. AB - Here we report on the effect of the mass transfer rate (k(t)) on the oxygen reduction reaction (ORR) catalyzed by Pt dendrimer-encapsulated nanoparticles (DENs) comprised of 147 and 55 atoms (Pt(147) and Pt(55)). The experiments were carried out using a dual-electrode microelectrochemical device, which enables the study of the ORR under high k(t) conditions with simultaneous detection of H(2)O(2). At low k(t) (0.02 to 0.12 cm s(-1)) the effective number of electrons involved in ORR, n(eff), is 3.7 for Pt(147) and 3.4 for Pt(55). As k(t) is increased, the mass-transfer-limited current for the ORR becomes significantly lower than the value predicted by the Levich equation for a 4-electron process regardless of catalyst size. However, the percentage of H(2)O(2) detected remains constant, such that n(eff) barely changes over the entire k(t) range explored (0.02 cm s(-1)). This suggests that mass transfer does not affect n(eff), which has implications for the mechanism of the ORR on Pt nanoparticles. Interestingly, there is a significant difference in n(eff) for the two sizes of Pt DENs (n(eff) = 3.7 and 3.5 for Pt(147) and Pt(55), respectively) that cannot be assigned to mass transfer effects and that we therefore attribute to a particle size effect. PMID- 22665773 TI - Photochemically driven redox chemistry induces protocell membrane pearling and division. AB - Prior to the evolution of complex biochemical machinery, the growth and division of simple primitive cells (protocells) must have been driven by environmental factors. We have previously demonstrated two pathways for fatty acid vesicle growth in which initially spherical vesicles grow into long filamentous vesicles; division is then mediated by fluid shear forces. Here we describe a different pathway for division that is independent of external mechanical forces. We show that the illumination of filamentous fatty acid vesicles containing either a fluorescent dye in the encapsulated aqueous phase, or hydroxypyrene in the membrane, rapidly induces pearling and subsequent division in the presence of thiols. The mechanism of this photochemically driven pathway most likely involves the generation of reactive oxygen species, which oxidize thiols to disulfide containing compounds that associate with fatty acid membranes, inducing a change in surface tension and causing pearling and subsequent division. This vesicle division pathway provides an alternative route for the emergence of early self replicating cell-like structures, particularly in thiol-rich surface environments where UV-absorbing polycyclic aromatic hydrocarbons (PAHs) could have facilitated protocell division. The subsequent evolution of cellular metabolic processes controlling the thiol:disulfide redox state would have enabled autonomous cellular control of the timing of cell division, a major step in the origin of cellular life. PMID- 22665774 TI - Anomalously weak solar convection. AB - Convection in the solar interior is thought to comprise structures on a spectrum of scales. This conclusion emerges from phenomenological studies and numerical simulations, though neither covers the proper range of dynamical parameters of solar convection. Here, we analyze observations of the wavefield in the solar photosphere using techniques of time-distance helioseismology to image flows in the solar interior. We downsample and synthesize 900 billion wavefield observations to produce 3 billion cross-correlations, which we average and fit, measuring 5 million wave travel times. Using these travel times, we deduce the underlying flow systems and study their statistics to bound convective velocity magnitudes in the solar interior, as a function of depth and spherical-harmonic degree l. Within the wavenumber band l < 60, convective velocities are 20-100 times weaker than current theoretical estimates. This constraint suggests the prevalence of a different paradigm of turbulence from that predicted by existing models, prompting the question: what mechanism transports the heat flux of a solar luminosity outwards? Advection is dominated by Coriolis forces for wavenumbers l < 60, with Rossby numbers smaller than approximately 10(-2) at r/R([symbol: see text]) = 0.96, suggesting that the Sun may be a much faster rotator than previously thought, and that large-scale convection may be quasi geostrophic. The fact that isorotation contours in the Sun are not coaligned with the axis of rotation suggests the presence of a latitudinal entropy gradient. PMID- 22665775 TI - Implanted adipose progenitor cells as physicochemical regulators of breast cancer. AB - Multipotent adipose-derived stem cells (ASCs) are increasingly used for regenerative purposes such as soft tissue reconstruction following mastectomy; however, the ability of tumors to commandeer ASC functions to advance tumor progression is not well understood. Through the integration of physical sciences and oncology approaches we investigated the capability of tumor-derived chemical and mechanical cues to enhance ASC-mediated contributions to tumor stroma formation. Our results indicate that soluble factors from breast cancer cells inhibit adipogenic differentiation while increasing proliferation, proangiogenic factor secretion, and myofibroblastic differentiation of ASCs. This altered ASC phenotype led to varied extracellular matrix (ECM) deposition and contraction thereby enhancing tissue stiffness, a characteristic feature of breast tumors. Increased stiffness, in turn, facilitated changes in ASC behavior similar to those observed with tumor-derived chemical cues. Orthotopic mouse studies further confirmed the pathological relevance of ASCs in tumor progression and stiffness in vivo. In summary, altered ASC behavior can promote tumorigenesis and, thus, their implementation for regenerative therapy should be carefully considered in patients previously treated for cancer. PMID- 22665776 TI - Temperature dependence of protein folding kinetics in living cells. AB - We measure the stability and folding rate of a mutant of the enzyme phosphoglycerate kinase (PGK) inside bone tissue cells as a function of temperature from 38 to 48 degrees C. To facilitate measurement in individual living cells, we developed a rapid laser temperature stepping method capable of measuring complete thermal melts and kinetic traces in about two min. We find that this method yields improved thermal melts compared to heating a sample chamber or microscope stage. By comparing results for six cells with in vitro data, we show that the protein is stabilized by about 6 kJ/mole in the cytoplasm, but the temperature dependence of folding kinetics is similar to in vitro. The main difference is a slightly steeper temperature dependence of the folding rate in some cells that can be rationalized in terms of temperature-dependent crowding, local viscosity, or hydrophobicity. The observed rate coefficients can be fitted within measurement uncertainty by an effective two-state model, even though PGK folds by a multistate mechanism. We validate the effective two-state model with a three-state free energy landscape of PGK to illustrate that the effective fitting parameters can represent a more complex underlying free energy landscape. PMID- 22665777 TI - Intersystem crossing and dynamics in O(3P) + C2H4 multichannel reaction: experiment validates theory. AB - The O((3)P) + C(2)H(4) reaction, of importance in combustion and atmospheric chemistry, stands out as a paradigm reaction involving triplet- and singlet-state potential energy surfaces (PESs) interconnected by intersystem crossing (ISC). This reaction poses challenges for theory and experiments owing to the ruggedness and high dimensionality of these potentials, as well as the long lifetimes of the collision complexes. Primary products from five competing channels (H + CH(2)CHO, H + CH(3)CO, H(2) + CH(2)CO, CH(3) + HCO, CH(2) + CH(2)O) and branching ratios (BRs) are determined in crossed molecular beam experiments with soft electron ionization mass-spectrometric detection at a collision energy of 8.4 kcal/mol. As some of the observed products can only be formed via ISC from triplet to singlet PESs, from the product BRs the extent of ISC is inferred. A new full-dimensional PES for the triplet state as well as spin-orbit coupling to the singlet PES are reported, and roughly half a million surface hopping trajectories are run on the coupled singlet-triplet PESs to compare with the experimental BRs and differential cross-sections. Both theory and experiment find almost equal contributions from the two PESs to the reaction, posing the question of how important is it to consider the ISC as one of the nonadiabatic effects for this and similar systems involved in combustion chemistry. Detailed comparisons at the level of angular and translational energy distributions between theory and experiment are presented for the two primary channel products, CH(3) + HCO and H + CH(2)CHO. The agreement between experimental and theoretical functions is excellent, implying that theory has reached the capability of describing complex multichannel nonadiabatic reactions. PMID- 22665778 TI - Metalloenzyme-like catalyzed isomerizations of sugars by Lewis acid zeolites. AB - Isomerization of sugars is used in a variety of industrially relevant processes and in glycolysis. Here, we show that hydrophobic zeolite beta with framework tin or titanium Lewis acid centers isomerizes sugars, e.g., glucose, via reaction pathways that are analogous to those of metalloenzymes. Specifically, experimental and theoretical investigations reveal that glucose partitions into the zeolite in the pyranose form, ring opens to the acyclic form in the presence of the Lewis acid center, isomerizes into the acyclic form of fructose, and finally ring closes to yield the furanose product. The zeolite catalysts provide processing advantages over metalloenzymes such as an ability to work at higher temperatures and in acidic conditions that allow for the isomerization reaction to be coupled with other important conversions. PMID- 22665779 TI - Mosquitoes survive raindrop collisions by virtue of their low mass. AB - In the study of insect flight, adaptations to complex flight conditions such as wind and rain are poorly understood. Mosquitoes thrive in areas of high humidity and rainfall, in which raindrops can weigh more than 50 times a mosquito. In this combined experimental and theoretical study, we here show that free-flying mosquitoes can survive the high-speed impact of falling raindrops. High-speed videography of those impacts reveals a mechanism for survival: A mosquito's strong exoskeleton and low mass renders it impervious to falling drops. The mosquito's low mass causes raindrops to lose little momentum upon impact and so impart correspondingly low forces to the mosquitoes. Our findings demonstrate that small fliers are robust to in-flight perturbations. PMID- 22665780 TI - Hydrophobic forces and the length limit of foldable protein domains. AB - To find the native conformation (fold), proteins sample a subspace that is typically hundreds of orders of magnitude smaller than their full conformational space. Whether such fast folding is intrinsic or the result of natural selection, and what is the longest foldable protein, are open questions. Here, we derive the average conformational degeneracy of a lattice polypeptide chain in water and quantitatively show that the constraints associated with hydrophobic forces are themselves sufficient to reduce the effective conformational space to a size compatible with the folding of proteins up to approximately 200 amino acids long within a biologically reasonable amount of time. This size range is in general agreement with the experimental protein domain length distribution obtained from approximately 1,200 proteins. Molecular dynamics simulations of the Trp-cage protein confirm this picture on the free energy landscape. Our analytical and computational results are consistent with a model in which the length and time scales of protein folding, as well as the modular nature of large proteins, are dictated primarily by inherent physical forces, whereas natural selection determines the native state. PMID- 22665781 TI - Accurate protein structure modeling using sparse NMR data and homologous structure information. AB - While information from homologous structures plays a central role in X-ray structure determination by molecular replacement, such information is rarely used in NMR structure determination because it can be incorrect, both locally and globally, when evolutionary relationships are inferred incorrectly or there has been considerable evolutionary structural divergence. Here we describe a method that allows robust modeling of protein structures of up to 225 residues by combining (1)H(N), (13)C, and (15)N backbone and (13)Cbeta chemical shift data, distance restraints derived from homologous structures, and a physically realistic all-atom energy function. Accurate models are distinguished from inaccurate models generated using incorrect sequence alignments by requiring that (i) the all-atom energies of models generated using the restraints are lower than models generated in unrestrained calculations and (ii) the low-energy structures converge to within 2.0 A backbone rmsd over 75% of the protein. Benchmark calculations on known structures and blind targets show that the method can accurately model protein structures, even with very remote homology information, to a backbone rmsd of 1.2-1.9 A relative to the conventional determined NMR ensembles and of 0.9-1.6 A relative to X-ray structures for well-defined regions of the protein structures. This approach facilitates the accurate modeling of protein structures using backbone chemical shift data without need for side-chain resonance assignments and extensive analysis of NOESY cross-peak assignments. PMID- 22665782 TI - Semimetallic dense hydrogen above 260 GPa. AB - Being the lightest and the most abundant element in the universe, hydrogen is fascinating to physicists. In particular, the conditions of its metallization associated with a possible superconducting state at high temperature have been a matter of much debate in the scientific community, and progress in this field is strongly correlated with the advancements in theoretical methods and experimental techniques. Recently, the existence of hydrogen in a metallic state was reported experimentally at room temperature under a pressure of 260-270 GPa, but was shortly after that disputed in the light of more experiments, finding either a semimetal or a transition to an other phase. With the aim to reconcile the different interpretations proposed, we propose by combining several computational techniques, such as density functional theory and the GW approximation, that phase III at ambient temperature of hydrogen is the Cmca-12 phase, which becomes a semimetal at 260 GPa . From phonon calculations, we demonstrate it to be dynamically stable; calculated electron-phonon coupling is rather weak and therefore this phase is not expected to be a high-temperature superconductor. PMID- 22665783 TI - Capturing directed molecular motion in the nuclear pore complex of live cells. AB - Nuclear pore complexes (NPCs) are gateways for nucleocytoplasmic exchange. Intrinsically disordered nucleoporins (Nups) form a selective filter inside the NPC, taking a central role in the vital nucleocytoplasmic transport mechanism. How such intricate meshwork relates to function and gives rise to a transport mechanism is still unclear. Here we set out to tackle this issue in intact cells by an established combination of fluorescence correlation spectroscopy and real time tracking of the center of mass of single NPCs. We find the dynamics of nucleoporin Nup153 to be regulated so as to produce rapid, discrete exchange between two separate positions within the NPC. A similar behavior is also observed for both karyopherinbeta1 transport-receptor and cargoes destined to nuclear import. Thus, we argue that directed Nup-mediated molecular motion may represent an intrinsic feature of the overall selective gating through intact NPCs. PMID- 22665784 TI - Enabling single-mode behavior over large areas with photonic Dirac cones. AB - Many of graphene's unique electronic properties emerge from its Dirac-like electronic energy spectrum. Similarly, it is expected that a nanophotonic system featuring Dirac dispersion (two conical bands touching at a single point, the so called Dirac point) will open a path to a number of important research avenues. To date, however, all proposed realizations of a photonic analog of graphene lack fully omnidirectional out-of-plane light confinement, which has prevented creating truly realistic implementations of this class of systems able to mimic the two-dimensional transport properties of graphene. Here we report on a novel route to achieve all-dielectric three-dimensional photonic materials featuring Dirac-like dispersion in a quasi-two-dimensional system. We further discuss how this finding could enable a dramatic enhancement of the spontaneous emission coupling efficiency (the beta-factor) over large areas, defying the common wisdom that the beta-factor degrades rapidly as the size of the system increases. These results might enable general new classes of large-area ultralow-threshold lasers, single-photon sources, quantum information processing devices and energy harvesting systems. PMID- 22665785 TI - Roles of cell confluency and fluid shear in 3-dimensional intracellular forces in endothelial cells. AB - We use a novel 3D inter-/intracellular force microscopy technique based on 3D traction force microscopy to measure the cell-cell junctional and intracellular tensions in subconfluent and confluent vascular endothelial cell (EC) monolayers under static and shear flow conditions. We found that z-direction cell-cell junctional tensions are higher in confluent EC monolayers than those in subconfluent ECs, which cannot be revealed in the previous 2D methods. Under static conditions, subconfluent cells are under spatially non-uniform tensions, whereas cells in confluent monolayers are under uniform tensions. The shear modulations of EC cytoskeletal remodeling, extracellular matrix (ECM) adhesions, and cell-cell junctions lead to significant changes in intracellular tensions. When a confluent monolayer is subjected to flow shear stresses with a high forward component comparable to that seen in the straight part of the arterial system, the intracellular and junction tensions preferentially increase along the flow direction over time, which may be related to the relocation of adherens junction proteins. The increases in intracellular tensions are shown to be a result of chemo-mechanical responses of the ECs under flow shear rather than a direct result of mechanical loading. In contrast, the intracellular tensions do not show a preferential orientation under oscillatory flow with a very low mean shear. These differences in the directionality and magnitude of intracellular tensions may modulate translation and transcription of ECs under different flow patterns, thus affecting their susceptibility for atherogenesis. PMID- 22665786 TI - Room temperature femtosecond X-ray diffraction of photosystem II microcrystals. AB - Most of the dioxygen on earth is generated by the oxidation of water by photosystem II (PS II) using light from the sun. This light-driven, four-photon reaction is catalyzed by the Mn(4)CaO(5) cluster located at the lumenal side of PS II. Various X-ray studies have been carried out at cryogenic temperatures to understand the intermediate steps involved in the water oxidation mechanism. However, the necessity for collecting data at room temperature, especially for studying the transient steps during the O-O bond formation, requires the development of new methodologies. In this paper we report room temperature X-ray diffraction data of PS II microcrystals obtained using ultrashort (< 50 fs) 9 keV X-ray pulses from a hard X-ray free electron laser, namely the Linac Coherent Light Source. The results presented here demonstrate that the "probe before destroy" approach using an X-ray free electron laser works even for the highly sensitive Mn(4)CaO(5) cluster in PS II at room temperature. We show that these data are comparable to those obtained in synchrotron radiation studies as seen by the similarities in the overall structure of the helices, the protein subunits and the location of the various cofactors. This work is, therefore, an important step toward future studies for resolving the structure of the Mn(4)CaO(5) cluster without any damage at room temperature, and of the reaction intermediates of PS II during O-O bond formation. PMID- 22665787 TI - Biphasic water splitting by osmocene. AB - The photochemical reactivity of osmocene in a biphasic water-organic solvent system has been investigated to probe its water splitting properties. The photoreduction of aqueous protons to hydrogen under anaerobic conditions induced by osmocene dissolved in 1,2-dichloroethane and the subsequent water splitting by the osmocenium metal-metal dimer formed during H(2) production were studied by electrochemical methods, UV-visible spectrometry, gas chromatography, and nuclear magnetic resonance spectroscopy. Density functional theory computations were used to validate the reaction pathways. PMID- 22665788 TI - Religion as a means to assure paternity. AB - The sacred texts of five world religions (Buddhism, Christianity, Hinduism, Islam, and Judaism) use similar belief systems to set limits on sexual behavior. We propose that this similarity is a shared cultural solution to a biological problem: namely male uncertainty over the paternity of offspring. Furthermore, we propose the hypothesis that religious practices that more strongly regulate female sexuality should be more successful at promoting paternity certainty. Using genetic data on 1,706 father-son pairs, we tested this hypothesis in a traditional African population in which multiple religions (Islam, Christianity, and indigenous) coexist in the same families and villages. We show that the indigenous religion enables males to achieve a significantly (P = 0.019) lower probability of cuckoldry (1.3% versus 2.9%) by enforcing the honest signaling of menstruation, but that all three religions share tenets aimed at the avoidance of extrapair copulation. Our findings provide evidence for high paternity certainty in a traditional African population, and they shed light on the reproductive agendas that underlie religious patriarchy. PMID- 22665789 TI - Interaction of structure-specific and promiscuous G-protein-coupled receptors mediates small-molecule signaling in Caenorhabditis elegans. AB - A chemically diverse family of small-molecule signals, the ascarosides, control developmental diapause (dauer), olfactory learning, and social behaviors of the nematode model organism, Caenorhabditis elegans. The ascarosides act upstream of conserved signaling pathways, including the insulin, TGF-beta, serotonin, and guanylyl cyclase pathways; however, the sensory processes underlying ascaroside function are poorly understood. Because ascarosides often are multifunctional and show strongly synergistic effects, characterization of their receptors will be essential for understanding ascaroside biology and may provide insight into molecular mechanisms that produce synergistic outcomes in small-molecule sensing. Based on DAF-8 immunoprecipitation, we here identify two G-protein-coupled receptors, DAF-37 and DAF-38, which cooperatively mediate ascaroside perception. daf-37 mutants are defective in all responses to ascr#2, one of the most potent dauer-inducing ascarosides, although this mutant responds normally to other ascarosides. In contrast, daf-38 mutants are partially defective in responses to several different ascarosides. Through cell-specific overexpression, we show that DAF-37 regulates dauer when expressed in ASI neurons and adult behavior when expressed in ASK neurons. Using a photoaffinity-labeled ascr#2 probe and amplified luminescence assays (AlphaScreen), we demonstrate that ascr#2 binds to DAF-37. Photobleaching fluorescent energy transfer assays revealed that DAF-37 and DAF-38 form heterodimers, and we show that heterodimerization strongly increases cAMP inhibition in response to ascr#2. These results suggest that that the ascarosides' intricate signaling properties result in part from the interaction of highly structure-specific G-protein-coupled receptors such as DAF 37 with more promiscuous G-protein-coupled receptors such as DAF-38. PMID- 22665790 TI - Late Middle Eocene primate from Myanmar and the initial anthropoid colonization of Africa. AB - Reconstructing the origin and early evolutionary history of anthropoid primates (monkeys, apes, and humans) is a current focus of paleoprimatology. Although earlier hypotheses frequently supported an African origin for anthropoids, recent discoveries of older and phylogenetically more basal fossils in China and Myanmar indicate that the group originated in Asia. Given the Oligocene-Recent history of African anthropoids, the colonization of Africa by early anthropoids hailing from Asia was a decisive event in primate evolution. However, the fossil record has so far failed to constrain the nature and timing of this pivotal event. Here we describe a fossil primate from the late middle Eocene Pondaung Formation of Myanmar, Afrasia djijidae gen. et sp. nov., that is remarkably similar to, yet dentally more primitive than, the roughly contemporaneous North African anthropoid Afrotarsius. Phylogenetic analysis suggests that Afrasia and Afrotarsius are sister taxa within a basal anthropoid clade designated as the infraorder Eosimiiformes. Current knowledge of eosimiiform relationships and their distribution through space and time suggests that members of this clade dispersed from Asia to Africa sometime during the middle Eocene, shortly before their first appearance in the African fossil record. Crown anthropoids and their nearest fossil relatives do not appear to be specially related to Afrotarsius, suggesting one or more additional episodes of dispersal from Asia to Africa. Hystricognathous rodents, anthracotheres, and possibly other Asian mammal groups seem to have colonized Africa at roughly the same time or shortly after anthropoids gained their first toehold there. PMID- 22665791 TI - Bioinspired nanofibers support chondrogenesis for articular cartilage repair. AB - Articular cartilage repair remains a significant and growing clinical challenge with the aging population. The native extracellular matrix (ECM) of articular cartilage is a 3D structure composed of proteinaceous fibers and a hydrogel ground substance that together provide the physical and biological cues to instruct cell behavior. Here we present fibrous scaffolds composed of poly(vinyl alcohol) and the biological cue chondroitin sulfate with fiber dimensions on the nanoscale for application to articular cartilage repair. The unique, low-density nature of the described nanofiber scaffolds allows for immediate cell infiltration for optimal tissue repair. The capacity for the scaffolds to facilitate cartilage-like tissue formation was evaluated in vitro. Compared with pellet cultures, the nanofiber scaffolds enhance chondrogenic differentiation of mesenchymal stems cells as indicated by increased ECM production and cartilage specific gene expression while also permitting cell proliferation. When implanted into rat osteochondral defects, acellular nanofiber scaffolds supported enhanced chondrogenesis marked by proteoglycan production minimally apparent in defects left empty. Furthermore, inclusion of chondroitin sulfate into the fibers enhanced cartilage-specific type II collagen synthesis in vitro and in vivo. By mimicking physical and biological cues of native ECM, the nanofiber scaffolds enhanced cartilaginous tissue formation, suggesting their potential utility for articular cartilage repair. PMID- 22665792 TI - Rho GTP exchange factor ARHGEF11 regulates the integrity of epithelial junctions by connecting ZO-1 and RhoA-myosin II signaling. AB - The organization of the apical junctional complex and its association with the cytoskeleton is essential for the function of epithelial cells. However, knowledge about the signaling pathways that regulate these processes is still fragmentary. Here we found that ARHGEF11, a member of the RGS-RhoGEF family, associates with tight junctions (TJs) by binding to ZO-1, but not to the highly homologous ZO-2, in polarized epithelial cells. In the early phases of cell-cell contact, ARHGEF11 was located at primordial adherens junctions, and then its localization was altered to TJs as epithelial polarity was established, much like ZO-1. Knockdown of ARHGEF11 reduced the phosphorylation of myosin light chain, retarding the assembly of cell-cell junctions and the development of the paracellular barrier. Furthermore, the simultaneous knockdown of ARHGEF11 and ZO 2 resulted in significant impairment of TJs and of the perijunctional actomyosin ring; similar defects arise when both ZO-1 and ZO-2 are depleted. These results suggest that ARHGEF11 mediates RhoA-myosin light chain signaling pathways at cell cell junctions, functioning in cooperation with ZO-1, to regulate the paracellular barrier and the organization of the apical junctional complex and perijunctional actomyosin ring of epithelial cells. PMID- 22665793 TI - Tobacco calmodulin-like protein provides secondary defense by binding to and directing degradation of virus RNA silencing suppressors. AB - RNA silencing (RNAi) induced by virus-derived double-stranded RNA (dsRNA), which is in a sense regarded as a pathogen-associated molecular pattern (PAMP) of viruses, is a general plant defense mechanism. To counteract this defense, plant viruses express RNA silencing suppressors (RSSs), many of which bind to dsRNA and attenuate RNAi. We showed that the tobacco calmodulin-like protein, rgs-CaM, counterattacked viral RSSs by binding to their dsRNA-binding domains and sequestering them from inhibiting RNAi. Autophagy-like protein degradation seemed to operate to degrade RSSs with the sacrifice of rgs-CaM. These RSSs could thus be regarded as secondary viral PAMPs. This study uncovered a unique defense system in which an rgs-CaM-mediated countermeasure against viral RSSs enhanced host antiviral RNAi in tobacco. PMID- 22665794 TI - Structure and regulon of Campylobacter jejuni ferric uptake regulator Fur define apo-Fur regulation. AB - The full regulatory potential of the ferric uptake regulator (Fur) family of proteins remains undefined despite over 20 years of study. We report herein an integrated approach that combines both genome-wide technologies and structural studies to define the role of Fur in Campylobacter jejuni (Cj). CjFur ChIP-chip assays identified 95 genomic loci bound by CjFur associated with functions as diverse as iron acquisition, flagellar biogenesis, and non-iron ion transport. Comparative analysis with transcriptomic data revealed that CjFur regulation extends beyond solely repression and also includes both gene activation and iron independent regulation. Computational analysis revealed the presence of an elongated holo-Fur repression motif along with a divergent holo-Fur activation motif. This diversity of CjFur DNA-binding elements is supported by the crystal structure of CjFur, which revealed a unique conformation of its DNA-binding domain and the absence of metal in the regulatory site. Strikingly, our results indicate that the apo-CjFur structure retains the canonical V-shaped dimer reminiscent of previously characterized holo-Fur proteins enabling DNA interaction. This conformation stems from a structurally unique hinge domain that is poised to further contribute to CjFur's regulatory functions by modulating the orientation of the DNA-binding domain upon binding of iron. The unique features of the CjFur crystal structure rationalize the binding sequence diversity that was uncovered during ChIP-chip analysis and defines apo-Fur regulation. PMID- 22665795 TI - Soluble epoxide hydrolase regulates hematopoietic progenitor cell function via generation of fatty acid diols. AB - Fatty acid epoxides are important lipid signaling molecules involved in the regulation of vascular tone and homeostasis. Tissue and plasma levels of these mediators are determined by the activity of cytochrome P450 epoxygenases and the soluble epoxide hydrolase (sEH), and targeting the latter is an effective way of manipulating epoxide levels in vivo. We investigated the role of the sEH in regulating the mobilization and proliferation of progenitor cells with vasculogenic/reparative potential. Our studies revealed that sEH down regulation/inhibition impaired the development of the caudal vein plexus in zebrafish, and decreased the numbers of lmo2/cmyb-positive progenitor cells therein. In mice sEH inactivation attenuated progenitor cell proliferation (spleen colony formation), but the sEH products 12,13-dihydroxyoctadecenoic acid (12,13-DiHOME) and 11,12- dihydroxyeicosatrienoic acid stimulated canonical Wnt signaling and rescued the effects of sEH inhibition. In murine bone marrow, the epoxide/diol content increased during G-CSF-induced progenitor cell expansion and mobilization, and both mobilization and spleen colony formation were reduced in sEH(-/-) mice. Similarly, sEH(-/-) mice showed impaired functional recovery following hindlimb ischemia, which was rescued following either the restoration of bone marrow sEH activity or treatment with 12,13-DiHOME. Thus, sEH activity is required for optimal progenitor cell proliferation, whereas long-term sEH inhibition is detrimental to progenitor cell proliferation, mobilization, and vascular repair. PMID- 22665796 TI - Aldosterone-independent regulation of the epithelial Na+ channel (ENaC) by vasopressin in adrenalectomized mice. AB - The epithelial Na(+) channel (ENaC) in the aldosterone-sensitive distal nephron (ASDN) is under negative-feedback regulation by the renin-angiotensin-aldosterone system in protection of sodium balance and blood pressure. We test here whether aldosterone is necessary and sufficient for ENaC expression and activity in the ASDN. Surprisingly, ENaC expression and activity are robust in adrenalectomized (Adx) mice. Exogenous mineralocorticoid increases ENaC activity equally well in control and Adx mice. Plasma [AVP] is significantly elevated in Adx vs. control mice. Vasopressin (AVP) stimulates ENaC. Inhibition of the V(2) AVP receptor represses ENaC activity in Adx mice. The absence of aldosterone combined with elevated AVP release compromises normal feedback regulation of ENaC in Adx mice in response to changes in sodium intake. These results demonstrate that aldosterone is sufficient but not necessary for ENaC activity in the ASDN. Aldosterone-independent stimulation by AVP shifts the role of ENaC in the ASDN from protecting Na(+) balance to promoting water reabsorption. This stimulation of ENaC likely contributes to the hyponatremia of adrenal insufficiency. PMID- 22665797 TI - Discovery of antimicrobial ribonucleotide reductase inhibitors by screening in microwell format. AB - Ribonucleotide reductase (RNR) catalyzes reduction of the four different ribonucleotides to their corresponding deoxyribonucleotides and is the rate limiting enzyme in DNA synthesis. RNR is a well-established target for the antiproliferative drugs Gemzar and Hydrea, for antisense therapy, and in combination chemotherapies. Surprisingly, few novel drugs that target RNR have emerged, partly because RNR activity assays are laboratory-intense and exclude high-throughput methodologies. Here, we present a previously undescribed PCR based assay for RNR activity measurements in microplate format. We validated the approach by screening a diverse library of 1,364 compounds for inhibitors of class I RNR from the opportunistic pathogen Pseudomonas aeruginosa, and we identified 27 inhibitors with IC(50) values from ~200 nM to 30 MUM. Interestingly, a majority of the identified inhibitors have been found inactive in human cell lines as well as in anticancer and in vivo tumor tests as reported by the PubChem BioAssay database. Four of the RNR inhibitors inhibited growth of P. aeruginosa, and two were also found to affect the transcription of RNR genes and to decrease the cellular deoxyribonucleotide pools. This unique PCR-based assay works with any RNR enzyme and any substrate nucleotide, and thus opens the door to high-throughput screening for RNR inhibitors in drug discovery. PMID- 22665798 TI - Induction of a G1-S checkpoint in fission yeast. AB - Entry into S phase is carefully regulated and, in most organisms, under the control of a G(1)-S checkpoint. We have previously described a G(1)-S checkpoint in fission yeast that delays formation of the prereplicative complex at chromosomal replication origins after exposure to UV light (UVC). This checkpoint absolutely depends on the Gcn2 kinase. Here, we explore the signal for activation of the Gcn2-dependent G(1)-S checkpoint in fission yeast. If some form of DNA damage can activate the checkpoint, deficient DNA repair should affect the length of the checkpoint-induced delay. We find that the cell-cycle delay differs in repair-deficient mutants from that in wild-type cells. However, the duration of the delay depends not only on the repair capacity of the cells, but also on the nature of the repair deficiency. First, the delay is abolished in cells that are deficient in the early steps of repair. Second, the delay is prolonged in repair mutants that fail to complete repair after the incision stage. We conclude that the G(1)-S delay depends on damage to the DNA and that the activating signal derives not from the initial DNA damage, but from a repair intermediate(s). Surprisingly, we find that activation of Gcn2 does not depend on the processing of DNA damage and that activated Gcn2 alone is not sufficient to delay entry into S phase in UVC-irradiated cells. Thus, the G(1)-S delay depends on at least two different inputs. PMID- 22665799 TI - Impaired function of the Tie-2 receptor contributes to vascular leakage and lethality in anthrax. AB - The anthrax lethal toxin (LT) enters host cells and enzymatically cleaves MAPKKs or MEKs. How these molecular events lead to death from anthrax remains poorly understood, but published reports suggest a direct effect of LT on vascular permeability. We have found that LT challenge in mice disrupts signaling through Tie-2, a tonically activated receptor tyrosine kinase in the endothelium. Genetic manipulations favoring Tie-2 activation enhanced interendothelial junctional contacts, prevented vascular leakage, and promoted survival following a lethal dose of LT. Cleavage of MEK1/2 was necessary for LT to induce endothelial barrier dysfunction, and activated Tie-2 signaled through the uncleaved fraction of MEKs to prevent LT's effects on the endothelium. Finally, primates infected with toxin secreting Bacillus anthracis bacilli developed a rapid and marked imbalance in the endogenous ligands that signal Tie-2, similar to that seen in LT-challenged mice. Our results show that B. anthracis LT blunts signaling through Tie-2, thereby weakening the vascular barrier and contributing to lethality of the disease. Measurement of circulating Tie-2 ligands and manipulation of Tie-2 activity may represent future prognostic and therapeutic avenues for humans exposed to B. anthracis. PMID- 22665800 TI - Perforin-dependent CD4+ T-cell cytotoxicity contributes to control a murine poxvirus infection. AB - CD4(+) T cells are generally regarded as helpers and regulators of the immune response. Although cytolytic CD4(+) T cells have been described, whether those generated during the course of a viral infection play a role in virus control remains unknown. Here we show that during acute infection with ectromelia virus, the mouse homolog of the human virus of smallpox, large numbers of CD4(+) T cells in the draining lymph node and liver of resistant mice have a cytotoxic phenotype. We also show that these cells kill targets in vivo in a perforin dependent manner and that mice with specific deficiency of perforin in CD4(+) T cells have impaired virus control. Thus, perforin-dependent CD4(+) T-cell killing of infected cells is an important mechanism of antiviral defense. PMID- 22665801 TI - Y chromosome mediates ribosomal DNA silencing and modulates the chromatin state in Drosophila. AB - Although the Drosophila Y chromosome is degenerated, heterochromatic, and contains few genes, increasing evidence suggests that it plays an important role in regulating the expression of numerous autosomal and X-linked genes. Here we use 15 Y chromosomes originating from a single founder 550 generations ago to study the role of the Y chromosome in regulating rRNA gene transcription, position-effect variegation (PEV), and the link among rDNA copy number, global gene expression, and chromatin regulation. Based on patterns of rRNA gene transcription indicated by transcription of the retrotransposon R2 that specifically inserts into the 28S rRNA gene, we show that X-linked rDNA is silenced in males. The silencing of X-linked rDNA expression by the Y chromosome is consistent across populations and independent of genetic background. These Y chromosomes also vary more than threefold in rDNA locus size and cause dramatically different levels of PEV suppression. The degree of suppression is negatively associated with the number and fraction of rDNA units without transposon insertions, but not with total rDNA locus size. Gene expression profiling revealed hundreds of differentially expressed genes among these Y chromosome introgression lines, as well as a divergent global gene expression pattern between the low-PEV and high-PEV flies. Our findings suggest that the Y chromosome is involved in diverse phenomena related to transcriptional regulation including X-linked rDNA silencing and suppression of PEV phenotype. These results further expand our understanding of the role of the Y chromosome in modulating global gene expression, and suggest a link with modifications of the chromatin state. PMID- 22665802 TI - Microbial interspecies electron transfer via electric currents through conductive minerals. AB - In anaerobic biota, reducing equivalents (electrons) are transferred between different species of microbes [interspecies electron transfer (IET)], establishing the basis of cooperative behaviors and community functions. IET mechanisms described so far are based on diffusion of redox chemical species and/or direct contact in cell aggregates. Here, we show another possibility that IET also occurs via electric currents through natural conductive minerals. Our investigation revealed that electrically conductive magnetite nanoparticles facilitated IET from Geobacter sulfurreducens to Thiobacillus denitrificans, accomplishing acetate oxidation coupled to nitrate reduction. This two-species cooperative catabolism also occurred, albeit one order of magnitude slower, in the presence of Fe ions that worked as diffusive redox species. Semiconductive and insulating iron-oxide nanoparticles did not accelerate the cooperative catabolism. Our results suggest that microbes use conductive mineral particles as conduits of electrons, resulting in efficient IET and cooperative catabolism. Furthermore, such natural mineral conduits are considered to provide ecological advantages for users, because their investments in IET can be reduced. Given that conductive minerals are ubiquitously and abundantly present in nature, electric interactions between microbes and conductive minerals may contribute greatly to the coupling of biogeochemical reactions. PMID- 22665803 TI - Extra-large letter spacing improves reading in dyslexia. AB - Although the causes of dyslexia are still debated, all researchers agree that the main challenge is to find ways that allow a child with dyslexia to read more words in less time, because reading more is undisputedly the most efficient intervention for dyslexia. Sophisticated training programs exist, but they typically target the component skills of reading, such as phonological awareness. After the component skills have improved, the main challenge remains (that is, reading deficits must be treated by reading more--a vicious circle for a dyslexic child). Here, we show that a simple manipulation of letter spacing substantially improved text reading performance on the fly (without any training) in a large, unselected sample of Italian and French dyslexic children. Extra-large letter spacing helps reading, because dyslexics are abnormally affected by crowding, a perceptual phenomenon with detrimental effects on letter recognition that is modulated by the spacing between letters. Extra-large letter spacing may help to break the vicious circle by rendering the reading material more easily accessible. PMID- 22665804 TI - Cold but not sympathomimetics activates human brown adipose tissue in vivo. AB - As potential activators of brown adipose tissue (BAT), mild cold exposure and sympathomimetic drugs have been considered as treatments for obesity and diabetes, but whether they activate the same pathways is unknown. In 10 healthy human volunteers, we found that the sympathomimetic ephedrine raised blood pressure, heart rate, and energy expenditure, and increased multiple circulating metabolites, including glucose, insulin, and thyroid hormones. Cold exposure also increased blood pressure and energy expenditure, but decreased heart rate and had little effect on metabolites. Importantly, cold increased BAT activity as measured by (18)F-fluorodeoxyglucose PET-CT in every volunteer, whereas ephedrine failed to stimulate BAT. Thus, at doses leading to broad activation of the sympathetic nervous system, ephedrine does not stimulate BAT in humans. In contrast, mild cold exposure stimulates BAT energy expenditure with fewer other systemic effects, suggesting that cold activates specific sympathetic pathways. Agents that mimic cold activation of BAT could provide a promising approach to treating obesity while minimizing systemic effects. PMID- 22665805 TI - RecQ helicase translocates along single-stranded DNA with a moderate processivity and tight mechanochemical coupling. AB - Maintenance of genome integrity is the major biological role of RecQ-family helicases via their participation in homologous recombination (HR)-mediated DNA repair processes. RecQ helicases exert their functions by using the free energy of ATP hydrolysis for mechanical movement along DNA tracks (translocation). In addition to the importance of translocation per se in recombination processes, knowledge of its mechanism is necessary for the understanding of more complex translocation-based activities, including nucleoprotein displacement, strand separation (unwinding), and branch migration. Here, we report the key properties of the ssDNA translocation mechanism of Escherichia coli RecQ helicase, the prototype of the RecQ family. We monitored the pre-steady-state kinetics of ATP hydrolysis by RecQ and the dissociation of the enzyme from ssDNA during single round translocation. We also gained information on the translocation mechanism from the ssDNA length dependence of the steady-state ssDNA-activated ATPase activity. We show that RecQ occludes 18 +/- 2 nt on ssDNA during translocation. The hydrolysis of ATP is noncooperative in the presence of ssDNA, indicating that RecQ active sites work independently during translocation. In the applied conditions, the enzyme hydrolyzes 35 +/- 4 ATP molecules per second during ssDNA translocation. RecQ translocates at a moderate processivity, with a mean run length of 100-320 nt on ssDNA. The determined tight mechanochemical coupling of 1.1 +/- 0.2 ATP consumed per nucleotide traveled indicates an inchworm-type mechanism. PMID- 22665806 TI - Regulation of innate CD8+ T-cell activation mediated by cytokines. AB - Virus-specific CD8(+) T cells develop the ability to function in an "innate" capacity by responding to a remarkable array of cytokines in a TCR-independent manner. Although several cytokines such as IL-12 and IL-18 have been identified as key regulators of CD8(+) T-cell activation, the role of other cytokines and the ways in which they interact with each other remain unclear. Here, we have used an unbiased, systematic approach to examine the effects of 1,849 cytokine combinations on virus-specific CD8(+) T-cell activation. This study identifies several unexpected cytokine combinations that synergize to induce antigen independent IFNgamma production and CD69 up-regulation by CD8(+) T cells in addition to cytokines that exhibit differential regulatory functions, with the ability to either enhance or inhibit T-cell IFNgamma production, depending on which cytokine partner is present. These findings underscore the complexity of cytokine interactions while also providing insight into the multifaceted regulatory network controlling virus-specific CD8(+) T-cell functions. PMID- 22665807 TI - Multisite phosphoregulation of Cdc25 activity refines the mitotic entrance and exit switches. AB - Cyclin-dependent kinase 1 (Cdk1) kinase dephosphorylation and activation by Cdc25 phosphatase are essential for mitotic entry. Activated Cdk1 phosphorylates Cdc25 and other substrates, further activating Cdc25 to form a positive feedback loop that drives the abrupt G2/mitosis switch. Conversely, mitotic exit requires Cdk1 inactivation and reversal of Cdk1 substrate phosphorylation. This dephosphorylation is mediated, in part, by Clp1/Cdc14, a Cdk1-antagonizing phosphatase, which reverses Cdk1 phosphorylation of itself, Cdc25, and other Cdk1 substrates. Thus, Cdc25 phosphoregulation is essential for proper G2-M transition, and its contributions to cell cycle control have been modeled based on studies using Xenopus and human cell extracts. Because cell extract systems only approximate in vivo conditions where proteins interact within dynamic cellular environments, here, we use Schizosaccharomyces pombe to characterize, both experimentally and mathematically, the in vivo contributions of Cdk1 mediated phosphorylation of Cdc25 to the mitotic transition. Through comprehensive mapping of Cdk1 phosphosites on Cdc25 and characterization of phosphomutants, we show that Cdc25 hyperphosphorylation by Cdk1 governs Cdc25 catalytic activation, the precision of mitotic entry, and unvarying cell length but not Cdc25 localization or abundance. We propose a mathematical model that explains Cdc25 regulation by Cdk1 through a distributive and disordered phosphorylation mechanism that ultrasensitively activates Cdc25. We also show that Clp1/Cdc14 dephosphorylation of Cdk1 sites on Cdc25 controls the proper timing of cell division, a mechanism that is likely due to the double negative feedback loop between Clp1/Cdc14 and Cdc25 that controls the abruptness of the mitotic exit switch. PMID- 22665808 TI - Primary somatosensory cortex discriminates affective significance in social touch. AB - Another person's caress is one of the most powerful of all emotional social signals. How much the primary somatosensory cortices (SIs) participate in processing the pleasantness of such social touch remains unclear. Although ample empirical evidence supports the role of the insula in affective processing of touch, here we argue that SI might be more involved in affective processing than previously thought by showing that the response in SI to a sensual caress is modified by the perceived sex of the caresser. In a functional MRI study, we manipulated the perceived affective quality of a caress independently of the sensory properties at the skin: heterosexual males believed they were sensually caressed by either a man or woman, although the caress was in fact invariantly delivered by a female blind to condition type. Independent analyses showed that SI encoded, and was modulated by, the visual sex of the caress, and that this effect is unlikely to originate from the insula. This suggests that current models may underestimate the role played by SI in the affective processing of social touch. PMID- 22665809 TI - Force of infection is key to understanding the epidemiology of Plasmodium falciparum malaria in Papua New Guinean children. AB - Genotyping Plasmodium falciparum parasites in longitudinal studies provides a robust approach to estimating force of infection (FOI) in the presence of superinfections. The molecular parameter (mol)FOI, defined as the number of new P. falciparum clones acquired over time, describes basic malaria epidemiology and is suitable for measuring outcomes of interventions. This study was designed to test whether (mol)FOI influenced the risk of clinical malaria episodes and how far (mol)FOI reflected environmental determinants of transmission, such as seasonality and small-scale geographical variation or effects of insecticide treated nets (ITNs). Two hundred sixty-four children 1-3 y of age from Papua New Guinea were followed over 16 mo. Individual parasite clones were tracked longitudinally by genotyping. On average, children acquired 5.9 (SD 9.6) new P. falciparum infections per child per y. (mol)FOI showed a pronounced seasonality, was strongly reduced in children using ITNs (incidence rate ratio, 0.49; 95% confidence interval, [0.38, 0.61]), increased with age, and significantly varied within villages (P = 0.001). The acquisition of new parasite clones was the major factor determining the risk of clinical illness (incidence rate ratio, 2.12; 95% confidence interval, [1.93, 2.31]). Adjusting for individual differences in (mol)FOI completely explained spatial variation, age trends, and the effect of ITN use. This study highlights the suitability of (mol)FOI as a measure of individual exposure and its central role in malaria epidemiology. It has substantial advantages over entomological measures in studies of transmission patterns, and could be used in analyses of host variation in susceptibility, in field efficacy trials of novel interventions or vaccines, and for evaluating intervention effects. PMID- 22665810 TI - Specific inactivation of two immunomodulatory SIGLEC genes during human evolution. AB - Sialic acid-recognizing Ig-like lectins (Siglecs) are signaling receptors that modulate immune responses, and are targeted for interactions by certain pathogens. We describe two primate Siglecs that were rendered nonfunctional by single genetic events during hominin evolution after our common ancestor with the chimpanzee. SIGLEC13 was deleted by an Alu-mediated recombination event, and a single base pair deletion disrupted the ORF of SIGLEC17. Siglec-13 is expressed on chimpanzee monocytes, innate immune cells that react to bacteria. The human SIGLEC17P pseudogene mRNA is still expressed at high levels in human natural killer cells, which bridge innate and adaptive immune responses. As both resulting pseudogenes are homozygous in all human populations, we resurrected the originally encoded proteins and examined their functions. Chimpanzee Siglec-13 and the resurrected human Siglec-17 recruit a signaling adapter and bind sialic acids. Expression of either Siglec in innate immune cells alters inflammatory cytokine secretion in response to Toll-like receptor-4 stimulation. Both Siglecs can also be engaged by two potentially lethal sialylated bacterial pathogens of newborns and infants, agents with a potential impact on reproductive fitness. Neanderthal and Denisovan genomes show human-like sequences at both loci, corroborating estimates that the initial pseudogenization events occurred in the common ancestral population of these hominins. Both loci also show limited polymorphic diversity, suggesting selection forces predating the origin of modern humans. Taken together, these data suggest that genetic elimination of Siglec-13 and/or Siglec-17 represents signatures of infectious and/or other inflammatory selective processes contributing to population restrictions during hominin origins. PMID- 22665811 TI - Critical features for biosynthesis, stability, and functionality of a G protein coupled receptor uncovered by all-versus-all mutations. AB - The structural features determining efficient biosynthesis, stability in the membrane and, after solubilization, in detergents are not well understood for integral membrane proteins such as G protein-coupled receptors (GPCRs). Starting from the rat neurotensin receptor 1, a class A GPCR, we generated a separate library comprising all 64 codons for each amino acid position. By combining a previously developed FACS-based selection system for functional expression [Sarkar C, et al. (2009) Proc Natl Acad Sci USA 105:14808-14813] with ultradeep 454 sequencing, we determined the amino acid preference in every position and identified several positions in the natural sequence that restrict functional expression. A strong accumulation of shifts, i.e., a residue preference different from wild type, is detected for helix 1, suggesting a key role in receptor biosynthesis. Furthermore, under selective pressure we observe a shift of the most conserved residues of the N-terminal helices. This unique data set allows us to compare the in vitro evolution of a GPCR to the natural evolution of the GPCR family and to observe how selective pressure shapes the sequence space covered by functional molecules. Under the applied selective pressure, several positions shift away from the wild-type sequence, and these improve the biophysical properties. We discuss possible structural reasons for conserved and shifted residues. PMID- 22665812 TI - Feedback regulation of plastidic acetyl-CoA carboxylase by 18:1-acyl carrier protein in Brassica napus. AB - Plant seed oil represents a major renewable source of reduced carbon, but little is known about the biochemical regulation of its synthesis. The goal of this research was to identify potential feedback regulation of fatty acid biosynthesis in Brassica napus embryo-derived cell cultures and to characterize both the feedback signals and enzymatic targets of the inhibition. Fatty acids delivered via Tween esters rapidly reduced the rate of fatty acid synthesis in a dose dependent and reversible manner, demonstrating the existence of feedback inhibition in an oil-accumulating tissue. Tween feeding did not affect fatty acid elongation in the cytosol or the incorporation of radiolabeled malonate into nascent fatty acids, which together pinpoint plastidic acetyl-CoA carboxylase (ACCase) as the enzymatic target of feedback inhibition. To identify the signal responsible for feedback, a variety of Tween esters were tested for their effects on the rate of fatty acid synthesis. Maximum inhibition was achieved upon feeding oleic acid (18:1) Tween esters that resulted in the intracellular accumulation of 18:1 free fatty acid, 18:1-CoA, and 18:1-acyl-carrier protein (ACP). Direct, saturable inhibition of ACCase enzyme activity was observed in culture extracts and in extracts of developing canola seeds supplemented with 18:1-ACP at physiological concentrations. A mechanism for feedback inhibition is proposed in which reduced demand for de novo fatty acids results in the accumulation of 18:1 ACP, which directly inhibits plastidic ACCase, leading to reduced fatty acid synthesis. Defining this mechanism presents an opportunity for mitigating feedback inhibition of fatty acid synthesis in crop plants to increase oil yield. PMID- 22665814 TI - Prediction of heart failure mortality in emergent care: a cohort study. AB - BACKGROUND: Heart failure contributes to millions of emergency department (ED) visits, but hospitalization-versus-discharge decisions are often not accompanied by prognostic risk quantification. OBJECTIVE: To derive and validate a model for acute heart failure mortality applicable in the ED. DESIGN: Clinical data abstraction with development of a broadly applicable multivariate risk index for 7-day death using initial vital signs, clinical and presentation features, and readily available laboratory tests. SETTING: Multicenter study of 86 hospitals in Ontario, Canada. PATIENTS: Population-based random sample of 12 591 patients presenting to the ED from 2004 to 2007. MEASUREMENTS: Death within 7 days of presentation. RESULTS: In the derivation cohort (n = 7433; mean age, 75.4 years [SD, 11.4]; 51.5% men), mortality risk increased with higher triage heart rate (adjusted odds ratio [OR], 1.15 [95% CI, 1.03 to 1.30] per 10 beats/min) and creatinine concentration (OR, 1.35 [CI, 1.14 to 1.60] per 1 mg/dL [88.4 umol/L]), and lower triage systolic blood pressure (OR, 1.52 [CI, 1.31 to 1.77] per 20 mm Hg) and initial oxygen saturation (OR, 1.16 [CI, 1.01 to 1.33] per 5%). Nonnormal serum troponin levels (OR, 2.75 [CI, 1.86 to 4.07]) were associated with increased mortality risk. Areas under the receiver-operating characteristic curves of the multivariate model were 0.805 for the derivation data set (bootstrap-corrected, 0.811) and 0.826 for validation data set (n = 5158; mean age, 75.7 years [SD, 11.4]; 51.6% men). In the derivation cohort, a multivariate index score stratified 7-day mortality with rates of 0.3%, 0.3%, 0.7%, and 1.9% in quintiles 1 to 4, respectively. Mortality rates in the 2 highest risk groups were 3.5% and 8.2% in deciles 9 and 10, respectively. LIMITATION: Left ventricular ejection fraction was not included in the model. CONCLUSION: A multivariate index comprising routinely collected variables stratified mortality risk with high discrimination in a broad group of patients with acute heart failure presenting to the ED. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research. PMID- 22665813 TI - Secondary gastrointestinal cancer in childhood cancer survivors: a cohort study. AB - BACKGROUND: Childhood cancer survivors develop gastrointestinal cancer more frequently and at a younger age than the general population, but the risk factors have not been well-characterized. OBJECTIVE: To determine the risk and associated risk factors for gastrointestinal subsequent malignant neoplasms (SMNs) in childhood cancer survivors. DESIGN: Retrospective cohort study. SETTING: The Childhood Cancer Survivor Study, a multicenter study of childhood cancer survivors diagnosed between 1970 and 1986. PATIENTS: 14 358 survivors of cancer diagnosed when they were younger than 21 years of age who survived for 5 or more years after the initial diagnosis. MEASUREMENTS: Standardized incidence ratios (SIRs) for gastrointestinal SMNs were calculated by using age-specific population data. Multivariate Cox regression models identified associations between risk factors and gastrointestinal SMN development. RESULTS: At median follow-up of 22.8 years (range, 5.5 to 30.2 years), 45 cases of gastrointestinal cancer were identified. The risk for gastrointestinal SMNs was 4.6-fold higher in childhood cancer survivors than in the general population (95% CI, 3.4 to 6.1). The SIR for colorectal cancer was 4.2 (CI, 2.8 to 6.3). The highest risk for gastrointestinal SMNs was associated with abdominal radiation (SIR, 11.2 [CI, 7.6 to 16.4]). However, survivors not exposed to radiation had a significantly increased risk (SIR, 2.4 [CI, 1.4 to 3.9]). In addition to abdominal radiation, high-dose procarbazine (relative risk, 3.2 [CI, 1.1 to 9.4]) and platinum drugs (relative risk, 7.6 [CI, 2.3 to 25.5]) independently increased the risk for gastrointestinal SMNs. LIMITATION: This cohort has not yet attained an age at which risk for gastrointestinal cancer is greatest. CONCLUSION: Childhood cancer survivors, particularly those exposed to abdominal radiation, are at increased risk for gastrointestinal SMNs. These findings suggest that surveillance of at risk childhood cancer survivors should begin at a younger age than that recommended for the general population. PRIMARY FUNDING SOURCE: National Cancer Institute. PMID- 22665815 TI - Effect of the Medicare Part D coverage gap on medication use among patients with hypertension and hyperlipidemia. AB - BACKGROUND: Prior studies of the Medicare Part D coverage gap are limited in generalizability and scope. OBJECTIVE: To determine the effect of the coverage gap on drugs used for asymptomatic (antihypertensive and lipid-lowering drugs) and symptomatic (pain relievers, acid suppressants, and antidepressants) conditions in elderly patients with hypertension and hyperlipidemia. DESIGN: Quasi-experimental study using pre-post design and contemporaneous control group. SETTING: Medicare claims files from 2005 and 2006 for 5% random sample of Medicare beneficiaries. PATIENTS: Part D plan enrollees with hypertension or hyperlipidemia aged 65 years or older who had no coverage, generic-only coverage, or both brand-name and generic coverage during the gap in 2006. Patients who were fully eligible for the low-income subsidy served as the control group. MEASUREMENTS: Monthly 30-day supply prescriptions available, medication adherence, and continuous medication gaps of 30 days or more for antihypertensive or lipid-lowering drugs; monthly 30-day supply prescriptions available for pain relievers, acid suppressants, or antidepressants before and after coverage gap entry. RESULTS: Patients with no gap coverage had a decrease in monthly antihypertensive and lipid-lowering drug prescriptions during the coverage gap. Nonadherence also increased in this group (antihypertensives: odds ratio [OR], 1.60 [95% CI, 1.50 to 1.71]; lipid-lowering drugs: OR, 1.59 [CI, 1.50 to 1.68]). The proportion of patients with no gap coverage who had continuous medication gaps in lipid-lowering medication use and antihypertensive use increased by an absolute 7.3% (OR, 1.38 [CI, 1.29 to 1.46]) and 3.2% (OR, 1.35 [CI, 1.25 to 1.45]), respectively, because of the coverage gap. Decreases in use were smaller for pain relievers and antidepressants and larger for acid suppressants in patients with no gap coverage. Patients with generic-only coverage had decreased use of cardiovascular medications but no change in use of drugs for symptomatic conditions. No measures changed in the brand-name and generic coverage groups. Results of sensitivity analyses were consistent with the main findings. LIMITATION: Because this study was nonrandomized, unobserved differences may still exist between study groups. CONCLUSION: The Part D coverage gap was associated with decreased use of medications for hypertension and hyperlipidemia in patients with no gap coverage and generic-only gap coverage. The proposed phasing out of the gap by 2020 will benefit such patients; however, use of low value medications may also increase. PRIMARY FUNDING SOURCE: Penn-Pfizer Alliance and American Heart Association. PMID- 22665816 TI - Conflicts of interest ethics: silencing expertise in the development of international clinical practice guidelines. AB - BACKGROUND: It is unclear whether global experts with financial conflicts of interest (FCOIs) should be included in, be excluded from, or have a limited role in developing international clinical practice guidelines (CPGs). Optimal management of FCOIs to ensure independent, expert CPGs remains ethically contested. OBJECTIVE: To manage FCOIs and examine whether an ethics framework with discussion recusal by experts with FCOIs affects deliberations and voting on a CPG. DESIGN: Development of an ethics framework grounded on transparency and proportional management of COIs, including self-recusal, evaluation of the effect on COIs and CPG process by quantification of voting on recommendations, and qualitative assessment of experts' ethics dialogue. SETTING: International consensus meeting to formulate a CPG in gastroenterology. PARTICIPANTS: 34 experts from 15 countries. MEASUREMENTS: Counting the votes of experts with and without declared FCOIs and qualitative assessment of ethics discussions. RESULTS: 62% of experts reported at least 1 FCOI. Eight out of 21 recommendations presented potential FCOIs. Experts with conflicts recused themselves from discussing 6 of the 8 recommendations, leaving a majority of nonconflicted discussants (median, 22; range, 19 to 26) for the 6 recommendations. Recusals did not affect voting outcomes but may have diluted the richness of the discussions. Ethics dialogue revealed accord on transparency but underscored challenges to proportional management of COIs beyond basic disclosure. Concerns about bias, COI definitions, expertise, and integrity express important international ethics questions. LIMITATION: Small participant numbers and application of the framework to only 1 meeting of 1 CPG. CONCLUSION: An ethics framework may help to identify and manage COIs and catalyze both ethics dialogue and innovative COI standards that seek to balance impartiality and expertise for trusted CPGs. Optimal balancing remains contested. Recommendations include frameworks, interdisciplinary analysis, and international policy initiatives to better manage COIs in the CPG process. PRIMARY FUNDING SOURCE: Canadian Association of Gastroenterology; European Association for Gastroenterology and Endoscopy; Asian Pacific Society of Digestive Endoscopy; and Institute of Diabetes, Metabolism, and Nutrition of the Canadian Institutes of Health Research. PMID- 22665818 TI - Big incision. PMID- 22665817 TI - The doughnut hole: it's about medication adherence. PMID- 22665819 TI - Cardiovascular mortality in women with obstructive sleep apnea with or without continuous positive airway pressure treatment. PMID- 22665820 TI - Virtual autopsy in the intensive care unit. PMID- 22665821 TI - Successful treatment of diffuse pulmonary lymphangiomatosis with bevacizumab. PMID- 22665822 TI - Summaries for patients. Increased risk for gastrointestinal cancer in childhood cancer survivors. PMID- 22665823 TI - In the clinic. Travel medicine. AB - The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including PIER (Physicians' Information and Education Resource) and MKSAP (Medical Knowledge and Self- Assessment Program). Annals of Internal Medicine editors develop In the Clinic from these primary sources in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of science writers and physician writers. Editorial consultants from PIER and MKSAP provide expert review of the content. Readers who are interested in these primary resources for more detail can consult http://pier.acponline.org, http://www.acponline.org/products_services/mksap/15/?pr31, and other resources referenced in each issue of In the Clinic. PMID- 22665824 TI - Directed evolution of the peroxidase activity of a de novo-designed protein. AB - Collections of de novo-designed proteins provide a unique opportunity to probe the functional potential of sequences that are stably folded, but were neither explicitly designed nor evolutionarily selected to perform any particular type of activity. A combinatorial library of folded proteins was designed previously using a strategy that exploits the binary patterning of polar and non-polar amino acids to drive sequences to fold into four-helix bundles. Although these novel four-helix bundles were not explicitly designed for function, previous characterization of several hundred arbitrarily chosen sequences showed that many of them bound the heme cofactor, and several of these novel heme proteins catalyzed peroxidase activity at levels substantially above background. Here, we show that these moderately active de novo heme proteins can serve as non-natural starting points for laboratory-based evolution: Random mutagenesis followed by color-based screening of a relatively small number (hundreds or thousands) of variants yielded novel sequences with improved peroxidase activity. Biochemical characterization of the purified proteins showed that the evolved variants were nearly 3-fold more active than the parental sequence. These results demonstrate that de novo-designed proteins can be utilized as a novel feedstock for the evolution of enzyme activity. PMID- 22665825 TI - Going the distance to improve the care span. PMID- 22665826 TI - The coming experiments in integrating and coordinating care for 'dual eligibles'. AB - The federal government and the states want to transform care for those enrolled in both Medicare and Medicaid. But will they move beneficiaries too fast into managed care plans? PMID- 22665827 TI - Six features of Medicare coordinated care demonstration programs that cut hospital admissions of high-risk patients. AB - As policy makers seek to slow the growth in Medicare spending, they have appropriately focused attention on beneficiaries with multiple chronic conditions. Many care coordination and disease management programs designed to improve beneficiaries' care and reduce their need for hospitalizations have been tested, but few have been successful. This study, however, found that four of eleven programs that were part of the Medicare Coordinated Care Demonstration reduced hospitalizations by 8-33 percent among enrollees who had a high risk of near-term hospitalization. The six approaches practiced by care coordinators in at least three of the four programs were as follows: supplementing telephone calls to patients with frequent in-person meetings; occasionally meeting in person with providers; acting as a communications hub for providers; delivering evidence-based education to patients; providing strong medication management; and providing timely and comprehensive transitional care after hospitalizations. When care management fees were included, the programs were essentially cost-neutral, but none of these programs generated net savings to Medicare. Our results suggest that incorporating these approaches into medical homes, accountable care organizations, and other policy initiatives could reduce hospitalizations and improve patients' lives. However, the approaches would save money only if care coordination fees were modest and organizations found cost-effective ways to deliver the interventions. PMID- 22665828 TI - Users of Medicaid home and community-based services are especially vulnerable to costly avoidable hospital admissions. AB - Although Medicaid's coverage of home and community-based services and the program's capacity to provide such services have increased markedly in recent years, relatively little is known about the population that uses these services. We combined Medicaid and Medicare data to characterize the national Medicaid population of service users by key demographic and health-related attributes. We also assessed one important dimension of their health outcomes: potentially avoidable hospital admissions. We found that in 2005 there were 2.2 million users of Medicaid home and community-based services-almost 4 percent of the total Medicaid population-and that two-thirds of these users were dually eligible for Medicare and Medicaid. Users of home and community-based services were particularly vulnerable to avoidable hospital admissions, compared to the full Medicaid and US populations, and these hospitalizations occur at substantial cost to public payers. For the dual eligibles using home and community-based services, Medicare pays most of the costs of these avoidable hospital stays. Our findings emphasize the need for further research to establish policies and practices that can best meet the needs of users of Medicaid home and community-based services. PMID- 22665829 TI - There is little experience and limited data to support policy making on integrated care for dual eligibles. AB - Coordinating care for the nine million elderly or disabled and low-income people who are dually eligible for Medicare and Medicaid is a pressing policy issue. To support the debate over this issue, we synthesized public data on how services are provided to dual eligibles receiving covered benefits in both programs. Our analysis confirmed that most dual-eligible beneficiaries receive benefits separately for each program through fee-for-service arrangements. Their enrollment in Medicare and Medicaid managed care is growing but still low, with highly uneven experiences across states. Few states or health plans have experience with coordinating care for dual eligibles within an integrated plan. These findings reinforce the need for caution in considering policies that would rapidly give states the responsibility for coordinating dual eligibles' care and coverage. We also found data gaps that warrant prompt attention in order to provide national-level oversight and improve the evidence base for debating and tracking policy changes. PMID- 22665830 TI - Dx for a careful approach to moving dual-eligible beneficiaries into managed care plans. AB - Policy makers are moving rapidly to develop and test reforms aimed at doing a better job of managing the costs and care for people dually eligible for Medicare and Medicaid. This commentary underscores the importance of pursuing new initiatives to address care coordination and spending concerns. It then focuses on key issues raised by proposals that would shift dual-eligible beneficiaries into managed care plans. The paper describes the heterogeneity and complexity of this population, emphasizing the need for approaches closely tied to the needs of particular subgroups of dual-eligible beneficiaries. It warns against moving too quickly, noting the time and resources required to build capacity to serve patients, secure provider networks, and develop an infrastructure for integrating and managing both Medicare and Medicaid services. The commentary cautions that optimistic savings assumptions might not materialize, raises questions about how savings will be allocated, and highlights the need for accountability as new models are being developed and tested to improve care for a population with complex needs. PMID- 22665831 TI - Gradual rebalancing of Medicaid long-term services and supports saves money and serves more people, statistical model shows. AB - States are shifting Medicaid spending on long-term services and supports from institutional to home and community-based services, a process known as rebalancing. Using fifteen years of state expenditure data, a statistical model was developed to assess the effect of rebalancing on overall spending for long term services and supports. The model indicates that spending is affected by the way rebalancing is implemented: Gradual rebalancing, by roughly two percentage points annually, can reduce spending by about 15 percent over ten years. More rapid rebalancing can save money, break even, or increase spending, depending on the pace and program specifics. Cuts to home and community-based services that hinder rebalancing are likely to increase, not decrease, overall spending on long term services and supports as people who were receiving these services shift into nursing homes. Because many states continue to experience budget crises, policy makers must think carefully before altering spending patterns for long-term services and supports and adopt strategies that particular states have used to successfully reduce overall spending, such as gradually shifting expenditures toward home and community-based waiver programs. PMID- 22665832 TI - Rapid reengineering of acute medical care for Medicare beneficiaries: the Medicare innovations collaborative. AB - In 2009 we described a geriatric service line or "portfolio" model of acute care based models to improve care and reduce costs for high-cost Medicare beneficiaries with multiple chronic conditions. In this article we report the early results of the Medicare Innovations Collaborative, a collaborative program of technical assistance and peer-to-peer exchange to promote the simultaneous adoption of multiple complex care models by hospitals and health systems. We found that organizations did in fact adopt and implement multiple complex care models simultaneously; that these care models were appropriately integrated and adapted so as to enhance their adoptability within the hospital or health care system; and that these processes occurred rapidly, in less than one year. Members indicated that the perceived prestige of participation in the collaborative helped create incentives for change among their systems' leaders and was one of the top two reasons for success. The Medicare Innovations Collaborative approach can serve as a model for health service delivery change, ultimately expanding beyond the acute care setting and into the community and often neglected postacute and long-term care arenas to redesign care for high-cost Medicare beneficiaries. PMID- 22665833 TI - How changes in Washington University's Medicare coordinated care demonstration pilot ultimately achieved savings. AB - As one of the initial fifteen participants in the Medicare Coordinated Care Demonstration, the Washington University School of Medicine in St. Louis was not able to demonstrate any reduction in hospitalizations or Medicare spending for the patients it served. In fact, the Washington University program increased total Medicare spending by 12 percent. But after a redesign, the results changed. The program stopped conducting care management of most of its patients via telephone from a remote site in California and, instead, served all patients through frequent phone and occasional in-person contact from local care managers in St. Louis. Care management efforts were focused especially on patients deemed at greatest risk of hospitalization, and stronger hospital transition planning and medication reconciliation were provided, among other changes. After that point, the program reduced hospitalizations by 12 percent and monthly Medicare spending by $217 per enrollee-more than offsetting the program's monthly $151 care management fee. The results underscore findings from the overall Medicare Coordinated Care Demonstration that suggest that programs with more in-person contacts were more likely than others to build trusting relationships with patients and providers, improve patient adherence to care plans, and address additional needs and barriers that entirely telephonic contacts had been unable to identify. The results also indicate that programs can be more effective by focusing on the highest-risk patients, for whom the largest savings resulted. PMID- 22665834 TI - Acute care for elders units produced shorter hospital stays at lower cost while maintaining patients' functional status. AB - Acute Care for Elders Units offer enhanced care for older adults in specially designed hospital units. The care is delivered by interdisciplinary teams, which can include geriatricians, advanced practice nurses, social workers, pharmacists, and physical therapists. In a randomized controlled trial of 1,632 elderly patients, length-of-stay was significantly shorter-6.7 days per patient versus 7.3 days per patient-among those receiving care in the Acute Care for Elders Unit compared to usual care. This difference produced lower total inpatient costs $9,477 per patient versus $10,451 per patient-while maintaining patients' functional abilities and not increasing hospital readmission rates. The practices of Acute Care for Elders Units, and the principles they embody, can provide hospitals with effective strategies for lowering costs while preserving quality of care for hospitalized elders. PMID- 22665835 TI - Costs for 'hospital at home' patients were 19 percent lower, with equal or better outcomes compared to similar inpatients. AB - Hospitals are the standard acute care venues in the United States, but hospital care is expensive and can pose health threats for older people. Albuquerque, New Mexico-based Presbyterian Healthcare Services adapted the Hospital at Home(r) model developed by the Johns Hopkins University Schools of Medicine and Public Health to provide acute hospital-level care within patients' homes. Patients show comparable or better clinical outcomes compared with similar inpatients, and they show higher satisfaction levels. Available to Medicare Advantage and Medicaid patients with common acute care diagnoses, this program achieved savings of 19 percent over costs for similar inpatients. These savings were predominantly derived from lower average length-of-stay and use of fewer lab and diagnostic tests compared with similar patients in hospital acute care. Hospital at Home advances the Triple Aim of clinical quality, affordability, and exceptional patient experience. PMID- 22665836 TI - How Kaiser Permanente uses video ethnography of patients for quality improvement, such as in shaping better care transitions. AB - Keeping patients and caregivers at the center of quality improvement is critical. Kaiser Permanente's Care Management Institute adapted video ethnography to achieve this aim, using video to capture interviews with-and observations of patients and caregivers, identify patient-centered improvement opportunities, and communicate them effectively to clinical and administrative leaders and front line staff. This method is particularly effective for helping understand the needs of frail elders, patients nearing the end of life, those with multiple chronic conditions, and other vulnerable people who are not well represented in focus groups and patient advisory councils. As part of an initiative to improve care transitions for elders with heart failure, video ethnography contributed to greatly reduced thirty-day hospital readmission rates, helping reduce readmissions at one medical center from 13.6 percent to 9 percent in six months. It also helped improve the reliability of the readmissions reduction program. When embedded within an established quality improvement framework, video ethnography can be an effective tool for innovating new solutions, improving existing processes, and spreading knowledge about how best to meet patient needs. PMID- 22665837 TI - Sharp rise in Medicare enrollees being held in hospitals for observation raises concerns about causes and consequences. AB - When it is not clear that an ill patient needs to be hospitalized, he or she may be placed "under observation" in a hospital for further evaluation and short-term treatment. These hospital observation services, often a kind of halfway point between emergency department treatment and full inpatient admission, have become a hotly debated policy issue and subject of lawsuits. Using Medicare enrollment and claims data nationwide, we documented a rising trend in the prevalence and duration of hospital observation services in the fee-for-service Medicare population during 2007-09, accompanied by a downward shift in inpatient admissions. As a result, the ratio of observation stays to inpatient admissions increased 34 percent, from an average of 86.9 observation stay events per 1,000 inpatient admissions per month in 2007 to 116.6 in 2009. Medicare beneficiaries were increasingly subjected to hospital observation care and treated as outpatients instead of inpatients, which can expose them to greater out-of-pocket expenses if they are eventually admitted to skilled nursing facilities. Additionally, the nearly one million beneficiaries receiving observation services each year were, on average, being held in observation for a longer period of time per episode-some for longer than seventy-two hours. The prevalence of observation services varied greatly across geographic regions and hospitals. This may be an unintended consequence of Medicare payment policies designed to constrain hospital admissions. Additional research is needed to pinpoint the drivers and consequences of this phenomenon, as is more clarity in clinical practice and Medicare policy guidelines regarding observation care. PMID- 22665838 TI - Despite 'welcome to Medicare' benefit, one in eight enrollees delay first use of part B services for at least two years. AB - Much research has focused on the possible overuse of health care services within Medicare, but there is also substantial evidence of underuse. In recent years, Congress has added a "welcome to Medicare" physician visit and a number of preventive services with no cost sharing to the Medicare benefit package to encourage early and appropriate use of services. We examined national longitudinal data on first claims for Part B services-the portion of Medicare that covers physician visits-to learn how people used these benefits. We found that 12 percent of people, or about one in eight, who enrolled in Medicare at age sixty-five waited more than two years before making their first use of care covered by Part B. In part, this delay reflected patterns of use before enrollment, in that people who sought preventive care before turning sixty-five continued to do so after enrolling in Medicare. Enrollees with Medigap coverage, higher household wealth, and a higher level of education typically received care under Part B sooner than others, whereas having greater tolerance for risk was more likely to lead enrollees to delay use of Part B services. Men had a lower probability of using Part B services early than women; blacks and members of other minority groups were less likely to use services early than whites. Although the "welcome to Medicare" checkup does not appear to have had a positive effect on use of services soon after enrollment, the percentage of beneficiaries receiving Part B services in the first two years after enrollment has steadily increased over time. Whether or not delays in receipt of care should be a considerable public policy concern may depend on what factors are leading specific categories of enrollees to delay care and how such delays affect health. PMID- 22665839 TI - Dignity-driven decision making: a compelling strategy for improving care for people with advanced illness. AB - The concept of dignity-driven decision making builds on previous efforts to define and develop patient- and family-centered care for people with advanced illness. More a framework than a rigid structure, the dignity-driven decision making model emphasizes the centrality of a collaborative process in which patients, most of whom are elderly; their families; and clinicians work together continuously to define the goals of care and how best to implement them. The early experiences of some organizations already practicing dignity-driven decision making in their care suggest that the model can improve patient care. Whether the system of care can produce enough savings to pay for its increased costs in the form of additional clinicians and managers is not yet known. Policy driven actions, such as payment reform and closer alignment of quality incentives with the model's objectives, will be integral to further development and dissemination of the model. PMID- 22665840 TI - Half of older Americans seen in emergency department in last month of life; most admitted to hospital, and many die there. AB - Emergency department use contributes to high end-of-life costs and is potentially burdensome for patients and family members. We examined emergency department use in the last months of life for patients age sixty-five or older who died while enrolled in a longitudinal study of older adults in the period 1992-2006. We found that 51 percent of the 4,158 [corrected] decedents visited the emergency department in the last month of life, and 75 percent in the last six months of life. Repeat visits were common. A total of 77 percent of the patients seen in the emergency department in the last month of life were admitted to the hospital, and 68 percent of those who were admitted died there. In contrast, patients who enrolled in hospice at least one month before death rarely visited the emergency department in the last month of life. Policies that encourage the preparation of patients and families for death and early enrollment in hospice may prevent emergency department visits at the end of life. PMID- 22665841 TI - US hospice industry experienced considerable turbulence from changes in ownership, growth, and shift to for-profit status. AB - The US hospice industry, which provides palliative and supportive care to patients with terminal illness, has undergone substantial changes during the last decade. The magnitude of these changes has not been fully captured in previous studies or reports. In this longitudinal study of hospices active in Medicare during 1999-2009, we analyzed Provider of Services files to understand key shifts in the industry. We found evidence of substantial turbulence. One-fifth of Medicare-certified hospices active in 1999 had closed or withdrawn from the program by 2009, and more than 40 percent had experienced one or more changes in ownership. The most prominent trend was the shift in ownership type from nonprofit to for-profit ownership. Four out of five Medicare-certified hospices that entered the marketplace between 2000 and 2009 were for-profit. Hospices also became larger, as the proportion with 100 or more full-time employees doubled to 5 percent from 1999 to 2009. Although each of the Census regions had more hospices in 2009 than in 1999, the geographic distribution of hospices in the country changed, with proportionally more in the South and West. The impact of all of these changes on cost and quality of hospice care, as well as patient access, remains a critical area for future research. PMID- 22665842 TI - Long-term care insurance demand limited by beliefs about needs, concerns about insurers, and care available from family. AB - In spite of the high costs and major financial risks involved in long-term care, the majority of older Americans do not own long-term care insurance. We conducted a survey designed to learn more about the role of the following four broad factors in affecting the demand for long-term care insurance: preferences and beliefs, such as notions about the likelihood that one will become disabled; substitutes for insurance, such as savings that could be spent on long-term care; substitutes for formal care, such as care provided by family members; and features of the private market, such as concerns about the high costs of coverage. We found evidence that each of these factors was important in explaining low demand for long-term care insurance. For example, people who believed they might need long-term care were more likely to purchase long-term care coverage. People who had alternative ways to pay for care, such as through savings, or those who could use unpaid care from family members, were less likely to purchase insurance. Features of the private market, such as people's lack of trust in insurers and the high cost of coverage, made people less likely to buy long-term care insurance. We conclude that policy interventions designed to address only one factor limiting the purchase of long-term care insurance are unlikely to dramatically increase demand for long-term care insurance. PMID- 22665843 TI - Reforming Medicare payments to skilled nursing facilities to cut incentives for unneeded care and avoiding high-cost patients. AB - Despite many changes made in 2010 and 2011 to Medicare's payment system for short term stays in skilled nursing facilities, a flawed payment structure continues to underpay facilities for certain types of patients and overpay for others. The flaws in the payment structure create incentives to selectively admit or refuse patients based on the type and complexity of their conditions, while payments that vary with level of use encourage providers to furnish therapy services, such as rehabilitation care, that some patients might not need. We propose an alternative payment design and demonstrate that it would dampen such incentives by making payments that are more closely matched to costs and based on characteristics of the patients treated. We propose replacing the existing therapy component of payment with one that varies payments according to the expected care needs of the patient and adding a separate payment component that covers drugs and other nontherapy ancillary services, such as support for patients on ventilators. We also propose adding an outlier policy to provide additional reimbursement for patients requiring exceptionally high-cost care. PMID- 22665844 TI - Creation of state basic health programs would lead to 4 percent fewer people churning between Medicaid and exchanges. AB - The Affordable Care Act gives states the option of creating a so-called Basic Health Program to provide health insurance coverage for individuals and families whose incomes are low but who do not qualify for Medicaid. The Basic Health Program is intended, in part, to decrease churning, or frequent movement between Medicaid and state-run health insurance exchanges, by increasing the income-based eligibility transition point between the two programs to 200 percent of the federal poverty level. We analyzed data from the 2008 panel of the Survey of Income and Program Participation and found that among adults likely to participate in Medicaid and exchanges, only somewhat fewer experienced a change in eligibility with a 200 percent federal poverty level eligibility threshold compared with the previous threshold of 138 percent. As a result, we found that a Basic Health Program would prevent churning for 1.8 million adults nationally each year-reducing by about 4 percent the expected churning of low-income Americans between Medicaid and exchanges within a year. Such programs would also decrease the risk that lower-income families would be subject to recouping of premium tax credits. But churning rates would remain very high, and additional policy steps would be required to minimize the effect of coverage disruptions. PMID- 22665845 TI - Federal employees health program experiences lack of competition in some areas, raising cost concerns for exchange plans. AB - The Affordable Care Act calls for creation of health insurance exchanges designed to provide private health insurance plan choices. The Federal Employees Health Benefits Program is a national model that to some extent resembles the planned exchanges. Both offer plans at the state level but are also overseen by the federal government. We examined the availability of plans and enrollment levels in the Federal Employees Health Benefits Program throughout the United States in 2010. We found that although plans were widely available, enrollment was concentrated in plans owned by just a few organizations, typically Blue Cross/Blue Shield plans. Enrollment was more concentrated in rural areas, which may reflect historical patterns of enrollment or lack of provider networks. Average biweekly premiums for an individual were lowest ($58.48) in counties where competition was extremely high, rising to $65.13 where competition was extremely low. To make certain that coverage sold through exchanges is affordable, policy makers may need to pay attention to areas where there is little plan competition and take steps through risk-adjustment policies or other measures to narrow differences in premiums and out-of-pocket expenses for consumers. PMID- 22665846 TI - 'They paved paradise and put up a parking lot'. AB - A doctor ponders his public health role when a patient loses a place to exercise and his health sharply deteriorates. PMID- 22665848 TI - The effect of electronic health records on test ordering. PMID- 22665849 TI - Factors affecting the use of electronic health records. PMID- 22665850 TI - Meaningful use of electronic health records. PMID- 22665851 TI - Electronic health records and improved care. PMID- 22665853 TI - Changes in urology standard of care. PMID- 22665854 TI - Adhering to the standard of care for prostate cancer. PMID- 22665856 TI - Uncertainties in diagnosing and treating lyme disease. PMID- 22665857 TI - Misinformation about lyme disease. PMID- 22665858 TI - Problematic assumptions in study of costs of care. PMID- 22665859 TI - Patient-centered medical homes. PMID- 22665861 TI - Cardiac disease in a case of precursor B acute lymphoblastic leukaemia with eosinophilia(ALL/Eo). AB - Acute lymphoblastic leukaemia (ALL) is the most common paediatric malignancy. However, it may rarely associate with eosinophilia. Patients with ALL associated with eosinophilia (ALL/ Eo) have a grave prognosis and higher incidence of cardiac complications compared to standard lymphoblastic leukaemia. Reports of ALL/Eo disclosed a few case with cardiac involvement early in the course of leukaemia. Here, the authors report a case of 13-year-old boy who presented with peripheral eosinophilia, chest pain and a large left ventricular mass early in the course of precursor B- cell ALL associated with eosinophilia. He received multi-agent chemotherapy but succumbed to death 25 days after chemotherapy due to a refractory cardio respiratory failure. PMID- 22665862 TI - Severe hypernatremic dehydration associated with cerebral venous and aortic thrombosis in the neonatal period. AB - Severe neonatal hypernatremia is an important electrolyte disorder that has serious effects. Cerebral venous thrombosis and aortic thrombosis are relatively rare in severe neonatal hypernatremic dehydration. The authors report a case of cerebral venous thrombosis, associated with aortic thrombosis revealed by dehydration in a 9-day-old boy. Diagnostic was performed using Doppler ultrasound and imaging techniques. Thrombosis was resolved after anticoagulation treatment with low-molecular weight heparin for 1 month, and then was substituted by oral anticoagulant. The case report is followed by a review of the literature dealing with clinical, aetiological and therapeutic aspects of neonatal thrombosis. PMID- 22665863 TI - Cardiac necklace in rheumatic heart disease. PMID- 22665864 TI - Diphyllobothrium nihonkaiense infection linked to chilled salmon consumption. AB - This is a case of a 40-year-old Japanese adult male who had acute onset watery diarrhoea with intermittent abdominal discomfort. Several days later, he found a 1 metre of tape-shaped object emerged from his anus and was eventually admitted to our hospital for further investigation. Stool examination revealed eggs of Diphyllobothrium with characteristic shape in his stool. After oral praziquantel administration, segments of proglottids were expelled from his anus. The proglottids were sent to the Infectious Disease Surveillance Centre of Japan, and DNA analysis of the proglottids proved to be those of Diphyllobothrium nihonkaiense. The patient confessed that he had an eating habit of chilled salmon. His diarrhoea and abdominal discomfort were completely diminished after 1 day of oral praziquantel administration. He was successfully discharged from the hospital a few days later admission without any complication of the disease and the side effect of treatment. PMID- 22665865 TI - Embryonic rhabdomyosarcoma presenting as Gradenigo's syndrome. AB - The authors report a previously undocumented case of parapharyngeal rhabdomyosarcoma presenting as Gradenigo's syndrome and review the history and aetiology of Gradenigo's syndrome. With sensitive diagnostic acumen this rare cause of Gradenigo's like syndrome was identified and correct treatment initiated. PMID- 22665866 TI - The hot rim sign on hepatobiliary scintigraphy (HIDA) with CT correlation. AB - An older male with multiple medical comorbidities presented to the emergency room after 3 days of worsening right upper quadrant pain. The patient had an elevated white blood cell count and mildly elevated liver functions. Initial ultrasound was equivocal and further imaging with CT scan was obtained. The CT scan was read as suggestive of cholecystitis, however a hepatobiliary scintigraphy (HIDA) scan was ordered for confirmation, as the patient was a poor operative candidate. The HIDA demonstrated no bile duct or small bowel activity on initial images or delays, however a classic 'hot rim' sign was present, confirming acute cholecystitis. The patient ultimately underwent percutaneous cholecystostomy with drainage for treatment where acute cholecystitis was confirmed. Upon retrospective review, the CT demonstrated hyperaemia surrounding the gallbladder fossa, which is the CT scan equivalent of a scintigraphic 'hot rim' sign. This is an uncommon example of a radiologic sign correlation between multiple imaging modalities. PMID- 22665867 TI - Pulmonary lymphangioleiomyomatosis associated with retroperitoneal lymphangioleiomyomas. AB - A 36-year-old woman presented with worsening symptoms of abdominal pain, diarrhoea, low fever, dyspnoea on exertion and bilateral leg during the last 2 months. Chest radiograph showed mild diffuse reticular pattern with preserved lung volumes. Lung high resolution CT disclosed multiple thin-walled lung cysts throughout the lungs bilaterally with no zonal predominance and with normal intervening parenchyma and abdominal CT revealed bilateral retrocrural and retroperitoneal hypodense masses. Imaging findings were consistent with lymphangioleiomyomatosis. PMID- 22665868 TI - Atrial fibrillation and pneumothorax after transthoracic needle lung biopsy. AB - An obese 65-year-old male smoker with chronic obstructive pulmonary disease developed an iatrogenic pneumothorax with pulmonary haemorrhage during an elective transthoracic needle biopsy of a pulmonary lesion. Successful re inflation was achieved with a chest drain which was then removed before transfer to the medical ward. He later developed persistent atrial fibrillation with breathlessness and haemoptysis. He was treated empirically for a pulmonary embolus, which was subsequently ruled out with CT pulmonary angiogram. Serial chest radiographs demonstrated recurrence of his pneumothorax and a chest drain was re-inserted. His atrial fibrillation was erroneously managed as supraventricular tachycardia, which was resistant to vagal manoeuvres and adenosine but later responded to intravenous amiodarone before a further relapse. Upon successful management of the pneumothorax, his atrial fibrillation terminated. This case highlighted the persistent and serious nature of complications posttransthoracic needle biopsy. PMID- 22665869 TI - Undiagnosed phaeochromocytoma masquerading as eclampsia. AB - The authors report the case of a previously well 34-year-old woman presenting with a hypertensive crises and a grand-mal seizure following elective caesarean section. Initial treatment of extreme hypertension, of a presumed eclamptic aetiology, with magnesium and labetalol was complicated by intermittent profound hypotensive episodes. This was accompanied by severe biventricular failure and fluctuating systemic vascular resistance. Abdominal ultrasound revealed a left suprarenal mass. A diagnosis of phaeochromocytoma was confirmed on abdominal CT and urinary assays. The patient was stabilised with alpha and beta blockade, was successfully extubated and subsequently had the tumour surgically excised. The cardiac function returned to normal on echocardiography and she has made a complete recovery. PMID- 22665870 TI - Bronchiolitis obliterans organising pneumonia: a consequence of breast radiotherapy. AB - The authors describe a case of 51-year-old woman who presented with breathlessness following radiotherapy for breast carcinoma. A chest radiograph and thoracic CT scan revealed extensive airspace consolidation affecting right upper and lower lobes. A trans-bronchial biopsy revealed evidence of foamy macrophages and fibroblastic plugs within alveoli, consistent with organising pneumonia. Indirect immunofluorescence microscopy revealed evidence of antiepithelial antibodies. Gradual but complete resolution occurred without any specific treatment. This case highlights the importance of considering radiation induced bronchiolitis obliterans organising pneumonia in the context of parenchymal shadowing following radiotherapy. Although corticosteroids are widely recommended for treatment, this case illustrates that organising pneumonia may resolve spontaneously. PMID- 22665871 TI - Bladder urothelial fissures: a reminder of a distressing disease. PMID- 22665872 TI - A patient with distinct dissociative and hallucinatory fugues. AB - A 62-year-old man presented with a history suggesting both dissociative fugue and a distinct fugue-like hallucination. The dissociative fugues included unplanned travel, loss of personal identity, inability to recall his past and amnesia for the fugue interval. The subjective fugues consisted of a stereotyped hallucination wherein he would travel to a social gathering place, meet his 'imaginary friends' and engage with them in conversation. He experienced the subjective fugues as if they were real, recognised them as hallucinations when he was normally conscious, and remembered them in great detail. A hallucinatory fugue episode occurred during video-EEG monitoring. The patient engaged in semipurposeful behaviour for which he had no memory, and the EEG demonstrated waking rhythms. Epilepsy, sleep disorder, factitious disorder and malingering were excluded from the differential diagnosis, leaving a patient with both dissociative and hallucinatory fugues, likely made possible by remote traumatic injury to limbic, arousal and motor circuits. PMID- 22665873 TI - Isolated anaemia as a manifestation of Rh isoimmunisation. AB - Rh isoimmunisation leads to haemolytic anaemia and hyperbilirubinaemia in the first h of life. Isolated early onset neonatal anaemia has rarely been reported. The authors describe the case of a term infant, born to an 'A' negative, second gravida mother. On the second day of life, pallor was noticed. His haemoglobin (Hb) was 6.8 g/dl, he had reticulocytosis and a positive direct antiglobulin test. However, he did not have a high total serum bilirubin (TSB) (87.2 MUmol/l). He was transfused with red blood cells and kept under phototherapy for 3 days. Three weeks later, he received another transfusion for severe anaemia (Hb 6 5 g/dl). During this period, he was never jaundiced and the maximum level of TSB was 122 MUmol/l. On follow-up, his Hb stabilised and he had no further problems. This report highlights the possibility of early onset anaemia without jaundice as the sole manifestation of Rh isoimmunisation. PMID- 22665874 TI - Spontaneous uterine rupture at 22 weeks' gestation in a multipara with previous hysteroscopic resection of fibroid. AB - A 34-year-old multiparous woman presented at 22(+6) weeks' gestation with severe abdominal pain which preceded a mechanical fall down the stairs. On admission, fetal movements were felt and fetal heart rate was detected by Doppler ultrasound. Over the course of 12 h, although she maintained her vital signs, repeat laboratory and radiological investigations suggested sinister intra abdominal pathology. Subsequently, fetal movements and heart rate ceased and the patient began to decompensate. A CT scan confirmed uterine rupture. Subsequent emergency laparotomy revealed a 2 l haemoperitoneum and lifeless fetoplacental unit in the abdominal cavity. It is postulated that this rupture occurred as a rare yet life-threatening complication of a hysteroscopic resection of fibroid that the patient underwent 1 year previously. There are no known published cases of a spontaneous uterine rupture following a hysteroscopic procedure at such an early gestation. The patient made a full physical recovery. PMID- 22665875 TI - Ketosis-prone type 2 diabetes mellitus in a patient with Sheehan's syndrome: a rare convergence of two distinct endocrine entities. AB - A 36-year-old housewife, previously diagnosed with Sheehan's syndrome on glucocorticoid and thyroxine replacement therapy, presented with unprovoked diabetic ketoacidosis. Ketoacidosis was corrected with intravenous fluids and insulin therapy. Further evaluation was suggestive of type 2 diabetes mellitus. On follow-up, she experienced repeated episodes of hypoglycaemia and insulin was tapered and stopped. Adequate glycaemic control was maintained with metformin monotherapy. PMID- 22665876 TI - Vesico-bullous rash caused by pompholyx eczema. PMID- 22665877 TI - Intravenous glomus tumour of the upper arm. AB - Glomus tumours are rare, benign tumours of the glomus body, most frequently located in the subungual region of digits, palms and soles, but they have been reported throughout the body. Our patient is a 65-year-old man who presented with a 3-year history of a very painful area on his left upper arm. The overlying skin was normal and there was no lesion to palpate, but the symptoms were very striking, warranting further investigation. An exploratory operation identified a prominent vein with a noticeable bulge in the vessel wall. The vein was ligated and excised. On dissection of the vein, a tumour was present within its lumen. Histological examination and immune profile of the tumour confirmed an intravascular glomus tumour. Following surgical excision, symptoms resolved. PMID- 22665878 TI - Psychosis in temporal lobe epilepsy: atypical presentation. AB - A 55-year-old lady was admitted following a concern raised by family members who had noticed a change in behaviour in terms of declining mood, paranoia with expression of belief that she was being bugged, also reported smelling perfume and after shave lotion. She had a prior diagnosis of bipolar mood disorder and was on lithium but remained no-compliant with her prescribed medication in the 10 weeks before admission. Upon admission, necessary investigations were performed including CT scan and EEG. Her CT was normal but EEG was grossly abnormal. Neurology consultation was sought and a sleep deprived EEG and MRI was ordered. Meanwhile, carbamezipine was commenced in view of the change in diagnosis to that of temporal lobe epilepsy. The patient responded very well to this regime and improved in all spheres. She was finally discharged with follow-up appointments with both neurology and psychiatry clinics. PMID- 22665879 TI - Haemangiopericytoma with no dural attachment. AB - The authors describe a case of a gentleman in his 40s who presented with a space occupying lesion in the right precentral gyrus which showed no dural attachment and was well circumscribed, both on imaging and at surgery. This lesion was histologically challenging to diagnose but favoured to be a haemangiopericytoma. The lack of dural attachment is unusual for this tumour type but is typically associated with metastases to the brain, and less commonly a solid primary central nervous system tumour. The authors propose that haemangiopericytoma should be regularly considered as a differential diagnosis of cerebral metastases so that inadequate preoperative anticipation and planning is not encountered. PMID- 22665880 TI - Death from axillary haemorrhage during haemodialysis in a patient with a history of microscopic polyangiitis. AB - An older female with a history of microscopic polyangiitis underwent haemodialysis through an end-to-side anastomosis between the left basilica vein and brachial artery. During the last haemodialysis session, repeated punctures induced haemorrhage that required brachial compression. Twenty min posthaemodialysis, haemorrhage had expanded from the axilla to the left lateral thorax. Autopsy disclosed axillary haematoma. The haemorrhage was not derived from punctured vessels or the left axillary artery. Although neither an alveolar nor a glomerular microscopic polyangiitis lesion was detected, fragility of the axillary small vessels due to microscopic polyangiitis, ageing, atherosclerosis and steroid therapy were underlying factors in the haematoma. Aspirin and heparin may have promoted haemorrhage, while shunt vessel stenosis with disturbed flow may have increased the axillary vessel pressure when the shunt vessels were compressed for haemostasis. This is the first report of a death due to haemorrhage from ruptured axillary vessels related to haemodialysis or microscopic polyangiitis. PMID- 22665881 TI - Chronic HIV-1 infection mimicking splenic malignant lymphoma on F-18 FDG-PET/CT. PMID- 22665882 TI - A 12-day-old male newborn with extensive vesicles and fever. AB - Neonatal varicella infection is a rare condition since vaccine introduction. The authors report the case of a 12-day-old male who presented with a fever and generalised vesicular eruption. The patient's mother had varicella infection 1 day before delivery without treatment. The neonate initially did not receive prophylaxis or treatment. He subsequently was started on intravenous acyclovir and recovered without further complications or sequelae. Prompt diagnosis and treatment for maternal prenatal varicella infection is necessary to prevent infection in the newborn, and healthcare provider awareness to avoid nosocomial transmission. PMID- 22665883 TI - Endovascular repair of juxtarenal aneurysms: real-world experience. PMID- 22665884 TI - Early results of fenestrated endovascular repair of juxtarenal aortic aneurysms in the United Kingdom. AB - BACKGROUND: Fenestrated endovascular repair of abdominal aortic aneurysms has been proposed as an alternative to open surgery for juxtarenal and pararenal abdominal aortic aneurysms. At present, the evidence base for this procedure is predominantly limited to single-center or single-operator series. The aim of this study was to present nationwide early results of fenestrated endovascular repair in the United Kingdom. METHODS AND RESULTS: All patients who underwent fenestrated endovascular repair between January 2007 and December 2010 at experienced institutions in the United Kingdom(>10 procedures) were retrospectively studied by use of the GLOBALSTAR database. Site-reported data relating to patient demographics, aneurysm morphology, procedural details, and outcome were recorded. Data from 318 patients were obtained from 14 centers. Primary procedural success was achieved in 99% (316/318); perioperative mortality was 4.1%, and intraoperative target vessel loss was observed in 5 of 889 target vessels (0.6%). The early reintervention (<30 days) rate was 7% (22/318). There were 11 deaths during follow-up; none were aneurysm-related. Survival by Kaplan Meier analysis was 94% (SE 0.01), 91% (0.02), and 89% (0.02) at 1, 2, and 3 years, respectively. Freedom from target vessel loss was 93% (0.02), 91% (0.02), and 85% (0.06), and freedom from late secondary intervention (>30 days) was 90% (0.02), 86% (0.03), and 70% (0.08) at 1, 2, and 3 years. CONCLUSIONS: In this national sample, fenestrated endovascular repair has been performed with a high degree of technical and clinical success. Late survival and target vessel patency are satisfactory. These results support continued use and evaluation of this technique for juxtarenal aneurysms, but illustrate the need for a more robust evidence base. PMID- 22665886 TI - Brown adipose tissue: mechanisms and potential therapeutic targets. PMID- 22665885 TI - Emerging role of circulating calcifying cells in the bone-vascular axis. PMID- 22665887 TI - Serial cardiac magnetic resonance imaging of a rapidly progressing liquefaction necrosis of mitral annulus calcification associated with embolic stroke. PMID- 22665890 TI - Letter by Varma regarding article, "Predictors of Response to Cardiac Resynchronization Therapy in The Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT)". PMID- 22665888 TI - Isolated cardiac involvement of B-cell acute lymphoblastic leukemia mimicking acute myocardial infarction with persistent broad ST-segment elevation. PMID- 22665891 TI - Astrophysical processes on the sun. AB - Over the past two decades, there have been a series of major solar space missions, namely Yohkoh, SOHO, TRACE, and in the past 5 years, STEREO, Hinode and SDO, studying various aspects of the Sun and providing images and spectroscopic data with amazing temporal, spatial and spectral resolution. Over the same period, the type and nature of numerical models in solar physics have been completely revolutionized as a result of widespread accessibility to parallel computers. These unprecedented advances on both observational and theoretical fronts have led to significant improvements in our understanding of many aspects of the Sun's behaviour and furthered our knowledge of plasma physics processes that govern solar and other astrophysical phenomena. In this Theme Issue, the current perspectives on the main astrophysical processes that shape our Sun are reviewed. In this Introduction, they are discussed briefly to help set the scene. PMID- 22665892 TI - The solar dynamo. AB - The origins of solar magnetism lie below the visible surface of the Sun, in the highly turbulent convection zone. Turbulent convection operates in conjunction with rotational shear, global circulations and intricate boundary layers to produce the rich diversity of magnetic activity we observe. Here, we review recent insights into the operation of the solar dynamo obtained from solar and stellar observations and numerical models. PMID- 22665893 TI - Magneto-convection. AB - Convection is the transport of energy by bulk mass motions. Magnetic fields alter convection via the Lorentz force, while convection moves the fields via the curl(v*B) term in the induction equation. Recent ground-based and satellite telescopes have increased our knowledge of the solar magnetic fields on a wide range of spatial and temporal scales. Magneto-convection modelling has also greatly improved recently as computers become more powerful. Three-dimensional simulations with radiative transfer and non-ideal equations of state are being performed. Flux emergence from the convection zone through the visible surface (and into the chromosphere and corona) has been modelled. Local, convectively driven dynamo action has been studied. The alteration in the appearance of granules and the formation of pores and sunspots has been investigated. Magneto convection calculations have improved our ability to interpret solar observations, especially the inversion of Stokes spectra to obtain the magnetic field and the use of helioseismology to determine the subsurface structure of the Sun. PMID- 22665894 TI - Magnetic flux emergence and associated dynamic phenomena in the Sun. AB - We present a review of the process of magnetic flux emergence in the Sun. We focus on observations and numerical experiments that explore the dynamical rise of magnetic fields from the solar interior to the corona. We describe the response of the highly stratified solar atmosphere on flux emergence and, consequently, we present a comprehensive picture of the coupling between solar dynamic events and flux emergence. We discuss potential applications of this process in other astrophysical environments. PMID- 22665895 TI - Numerical models of sunspot formation and fine structure. AB - Sunspots are central to our understanding of solar (and stellar) magnetism in many respects. On the large scale, they link the magnetic field observable in the photosphere to the dynamo processes operating in the solar interior. Properly interpreting the constraints that sunspots impose on the dynamo process requires a detailed understanding of the processes involved in their formation, dynamical evolution and decay. On the small scale, they give an insight into how convective energy transport interacts with the magnetic field over a wide range of field strengths and inclination angles, leading to sunspot fine structure observed in the form of umbral dots and penumbral filaments. Over the past decade, substantial progress has been made on both observational and theoretical sides. Advanced ground- and space-based observations have resolved, for the first time, the details of umbral dots and penumbral filaments and discovered similarities in their substructures. Numerical models have advanced to the degree that simulations of entire sunspots with sufficient resolution to resolve sunspot fine structure are feasible. A combination of improved helioseismic inversion techniques with seismic forward modelling provides new views on the subsurface structure of sunspots. In this review, we summarize recent progress, with particular focus on numerical modelling. PMID- 22665896 TI - The quiet-Sun photosphere and chromosphere. AB - The overall structure and the fine structure of the solar photosphere outside active regions are largely understood, except possibly the important roles of a turbulent near-surface dynamo at its bottom, internal gravity waves at its top and small-scale vorticity. Classical one-dimensional static radiation-escape modelling has been replaced by three-dimensional time-dependent magento hydrodynamic simulations that come closer to reality. The solar chromosphere, in contrast, remains little understood, although its pivotal role in coronal mass and energy loading makes it a principal research area. Its fine structure defines its overall structure, so that hard-to-observe and hard-to-model small-scale dynamical processes are key to understanding. However, both chromospheric observation and chromospheric simulation presently mature towards the required sophistication. Open-field features seem of greater interest than easier-to-see closed-field features. PMID- 22665897 TI - The Sun's global magnetic field. AB - Our present-day understanding of solar and stellar magnetic fields is discussed from both an observational and theoretical viewpoint. To begin with, observations of the Sun's large-scale magnetic field are described, along with recent advances in measuring the spatial distribution of magnetic fields on other stars. Following this, magnetic flux transport models used to simulate photospheric magnetic fields and the wide variety of techniques used to deduce global coronal magnetic fields are considered. The application and comparison of these models to the Sun's open flux, hemispheric pattern of solar filaments and coronal mass ejections are then discussed. Finally, recent developments in the construction of steady-state global magnetohydrodynamic models are considered, along with key areas of future research. PMID- 22665898 TI - Theory of magnetic reconnection in solar and astrophysical plasmas. AB - Magnetic reconnection is a fundamental process in a plasma that facilitates the release of energy stored in the magnetic field by permitting a change in the magnetic topology. In this paper, we present a review of the current state of understanding of magnetic reconnection. We discuss theoretical results regarding the formation of current sheets in complex three-dimensional magnetic fields and describe the fundamental differences between reconnection in two and three dimensions. We go on to outline recent developments in modelling of reconnection with kinetic theory, as well as in the magnetohydrodynamic framework where a number of new three-dimensional reconnection regimes have been identified. We discuss evidence from observations and simulations of Solar System plasmas that support this theory and summarize some prominent locations in which this new reconnection theory is relevant in astrophysical plasmas. PMID- 22665899 TI - Magnetohydrodynamic waves and coronal seismology: an overview of recent results. AB - Recent observations have revealed that magnetohydrodynamic (MHD) waves and oscillations are ubiquitous in the solar atmosphere, with a wide range of periods. We give a brief review of some aspects of MHD waves and coronal seismology that have recently been the focus of intense debate or are newly emerging. In particular, we focus on four topics: (i) the current controversy surrounding propagating intensity perturbations along coronal loops, (ii) the interpretation of propagating transverse loop oscillations, (iii) the ongoing search for coronal (torsional) Alfven waves, and (iv) the rapidly developing topic of quasi-periodic pulsations in solar flares. PMID- 22665900 TI - A contemporary view of coronal heating. AB - Determining the heating mechanism (or mechanisms) that causes the outer atmosphere of the Sun, and many other stars, to reach temperatures orders of magnitude higher than their surface temperatures has long been a key problem. For decades, the problem has been known as the coronal heating problem, but it is now clear that 'coronal heating' cannot be treated or explained in isolation and that the heating of the whole solar atmosphere must be studied as a highly coupled system. The magnetic field of the star is known to play a key role, but, despite significant advancements in solar telescopes, computing power and much greater understanding of theoretical mechanisms, the question of which mechanism or mechanisms are the dominant supplier of energy to the chromosphere and corona is still open. Following substantial recent progress, we consider the most likely contenders and discuss the key factors that have made, and still make, determining the actual (coronal) heating mechanism (or mechanisms) so difficult. PMID- 22665901 TI - Solar flares and energetic particles. AB - Solar flares are now observed at all wavelengths from gamma-rays to decametre radio waves. They are commonly associated with efficient production of energetic particles at all energies. These particles play a major role in the active Sun because they contain a large amount of the energy released during flares. Energetic electrons and ions interact with the solar atmosphere and produce high energy X-rays and gamma-rays. Energetic particles can also escape to the corona and interplanetary medium, produce radio emissions (electrons) and may eventually reach the Earth's orbit. I shall review here the available information on energetic particles provided by X-ray/gamma-ray observations, with particular emphasis on the results obtained recently by the mission Reuven Ramaty High Energy Solar Spectroscopic Imager. I shall also illustrate how radio observations contribute to our understanding of the electron acceleration sites and to our knowledge on the origin and propagation of energetic particles in the interplanetary medium. I shall finally briefly review some recent progress in the theories of particle acceleration in solar flares and comment on the still challenging issue of connecting particle acceleration processes to the topology of the complex magnetic structures present in the corona. PMID- 22665902 TI - Retraction. Green waxes, adhesives and lubricants. PMID- 22665903 TI - Vandetanib for the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease: U.S. Food and Drug Administration drug approval summary. AB - On April 6, 2011, the U.S. Food and Drug Administration approved vandetanib (Caprelsa tablets; AstraZeneca Pharmaceuticals LP) for the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable, locally advanced, or metastatic disease. Vandetanib is the first drug approved for this indication, and this article focuses on the basis of approval. Approval was based on the results of a double-blind trial conducted in patients with medullary thyroid carcinoma. Patients were randomized 2:1 to vandetanib, 300 mg/d orally (n = 231), or to placebo (n = 100). The primary objective was demonstration of improvement in progression-free survival (PFS) with vandetanib compared with placebo. Other endpoints included evaluation of overall survival and objective response rate. The PFS analysis showed a marked improvement for patients randomized to vandetanib (hazard ratio = 0.35; 95% confidence interval, 0.24-0.53; P < 0.0001). The objective response rate for the vandetanib arm was 44% compared with 1% for the placebo arm. The most common grade 3 and 4 toxicities (>5%) were diarrhea and/or colitis, hypertension and hypertensive crisis, fatigue, hypocalcemia, rash, and corrected QT interval (QTc) prolongation. This approval was based on a statistically significant and clinically meaningful improvement in PFS. Given the toxicity profile, which includes prolongation of the QT interval and sudden death, only prescribers and pharmacies certified through the vandetanib Risk Evaluation Mitigation Strategy Program are able to prescribe and dispense vandetanib. Treatment-related risks should be taken into account when considering the use of vandetanib in patients with indolent, asymptomatic, or slowly progressing disease. PMID- 22665904 TI - A replication study and genome-wide scan of single-nucleotide polymorphisms associated with pancreatic cancer risk and overall survival. AB - PURPOSE: To explore the effects of single-nucleotide polymorphisms (SNP) on pancreatic cancer risk and overall survival (OS). EXPERIMENTAL DESIGN: The germ line DNA of 531 pancreatic cancer cases and 305 healthy controls from a hospital based study was genotyped at SNPs previously reported to be associated with pancreatic cancer risk or clinical outcome. We analyzed putative risk SNPs for replication of their reported effects on risk and tested for novel effects on OS. Similarly, we analyzed putative survival-associated SNPs for replication of their reported effects on OS and tested for novel effects on risk. Finally, we conducted a genome-wide association study (GWAS) of OS using a subset of 252 cases, with two subsequent validation sets of 261 and 572 patients, respectively. RESULTS: Among seven risk SNPs analyzed, two (rs505922 and rs9543325) were associated with risk (P < 0.05). Among 24 survival-associated SNPs analyzed, one (rs9350) was associated with OS (P < 0.05). No putative risk SNPs or putative survival-associated SNPs were found to be associated with OS or risk, respectively. Furthermore, our GWAS identified a novel SNP [rs1482426, combined stage I and II, P = 1.7 * 10(-6), per-allele HR, 1.74; 95% confidence interval (CI), 1.38-2.18] to be putatively associated with OS. CONCLUSIONS: The effects of SNPs on pancreatic cancer risk and OS were replicated in our study, although further work is necessary to understand the functional mechanisms underlying these effects. More importantly, the putative association with OS identified by GWAS suggests that GWAS may be useful in identifying SNPs associated with clinical outcome in pancreatic cancer. PMID- 22665905 TI - A 77-year-old female with a giant hepatic cyst. AB - A 77-year-old female presented with high blood pressure noted at home. She was having abdominal pain and distension for several years but attributed it to old age and ignored the symptoms. CT scan revealed a giant hepatic liver cyst. The cyst was subsequently excised via laparoscopic unroofing. The patient did well post op and her symptoms were alleviated. PMID- 22665906 TI - Systemic sarcoidosis with caseating granuloma. AB - Sarcoidosis is a multi-systemic disease, the diagnosis of which depends on the presence of non-necrotising granulomas in a biopsy specimen. However, variants such as necrotising sarcoid granuloma make it difficult to differentiate the disease from other infectious processes, especially tuberculosis. Here the authors describe the case of a 58-year-old Iranian woman who developed granulomas with extensive necrosis in a systemic sarcoidosis that affected the lung, liver and spleen. These findings led to a diagnosis of tuberculosis and delayed appropriate treatment. PMID- 22665907 TI - Simple sling for hand infection. AB - In the absence of a Bradford sling, I constructed a simple sling to elevate an infected hand from medical equipment that was readily available on the ward. The results were so successful and the experience so comfortable for the patient that the technique should be explained and made clear for other doctors. In this particular case, a serious side effect was avoided namely infection of nearby indwelling metalwork. The patient contacted us afterwards to say how well he felt, he had been looked after and how comfortable the equipment had been to use during his stay in hospital. PMID- 22665908 TI - Sepsis, meningitis and cerebral abscesses caused by Citrobacter koseri. AB - After a 36-week diamniotic dichorionic gestation, an infant was delivered by elective caesarean section due to growth restriction and altered diastolic flow in the umbilical artery. Birth weight was 2140 g. The patient was admitted for exclusive parenteral nutrition, with umbilical venous catheter placement. Sinus tachycardia and temperature instability with positive inflammatory markers occurred at 51 h. Penicillin and gentamicin were started, but 6 h later septic shock with disseminated intravascular coagulation was noted. Vancomycin and meropenem were started and penicillin suspended. Citrobacter koseri was isolated from blood culture. Generalised clonic convulsions occurred on day 4, and an electroencephalogram revealed severe encephalic dysfunction. Cerebrospinal fluid cytochemical analysis was suggestive of meningitis, although culture was negative. Cefotaxime was added to the drug regimen. Cranioencephalic MR showed a temporal abscess and diffuse hemispheric destruction, with no indications for neurosurgery. After 6 weeks of therapy, neuroimaging follow-up showed multiloculated cystic encephalomalacia. Currently, the patient is 14 months old with axial hypotonia and decreased movements. The source of infection has not been determined. Nosocomial infection cannot be excluded and vertical transmission is unlikely. PMID- 22665909 TI - Cytomegalovirus-induced haemophagocytic lymphohistiocytosis syndrome. PMID- 22665910 TI - Asymptomatic omental granuloma following spillage of gallstones during laparoscopic cholecystectomy protects patients and influences surgeons' decisions: a review. AB - Spillage of gallstones in the peritoneal cavity during laparoscopic cholecystectomy (LC) occurs at rates varying from 5.7% to 16%. These gallstones often cannot be retrieved and can cause early and late abscesses at rates ranging from 0.08% to 1.4%. The case of an 86-year-old woman with colon cancer is described because during an elective right hemicolectomy a granuloma of the omentum with retained gallstones from LC performed 8 years earlier was unexpectedly found. Importantly, the gallstones were found high up in the abdominal cavity. Moreover, this report reaffirms the excellent response of the peritoneal cavity defence mechanisms for protecting patients against gallstones through asymptomatic omental granuloma. Current data indicate that every effort should be made to retrieve spilled gallstones, but routine conversion to an open cholecystectomy is not recommended. Identifying factors that impair host defence mechanisms should help surgeons' decision-making. PMID- 22665911 TI - A man with leonine facies. PMID- 22665912 TI - Enterocutaneous fistula as early presentation of Crohn's disease in an adult woman. AB - Crohn's disease is a chronic transmural inflammatory process that primarily affects the gastrointestinal tract, with several extra-intestinal manifestations. Though patients usually present with vague abdominal pain, initial presentation can be at an advanced stage or with extra-intestinal pathology. The authors report the case of a 59-year-old woman, who presented with a tubo-ovarian abscess that resulted in a protracted non-healing enterocutaneous fistula, which was eventually diagnosed as Crohn's disease approximately 2 years after initial presentation. Relevant literature is reviewed, as well as time-points where an earlier diagnosis could have been made thereby underscoring the importance of considering Crohn's Disease in a non-healing enterocutaneous fistula in an otherwise asymptomatic patient. PMID- 22665913 TI - Posterior pharyngeal wall carcinoma presenting as sudden onset bilateral upper limb radiculopathy. AB - This report describes the case of an elderly gentleman who presented with sudden onset bilateral upper limb radiculopathy and neck stiffness. On neck radiography, erosion of the fourth cervical vertebral body was seen. Further evaluation revealed the cause to be a moderately differentiated squamous cell carcinoma of the posterior pharyngeal wall. In spite of prompt initiation of radiation therapy with concurrent steroids, the patient died of progressive disease within 3 weeks of initial presentation. PMID- 22665914 TI - Isolated central nervous system relapse in a patient with diffuse large B cell lymphoma. PMID- 22665915 TI - Incidental detection of late presenting co-arctation of the aorta on chest x-ray: the importance of rib notching. AB - A 31-year-old obese male presented to the emergency department with symptoms and signs suggestive of a viral upper respiratory tract illness with a background of low exercise tolerance. Rib notching was identified on plain film chest radiography and subsequent CT of the thorax identified a moderately tight 2-mm juxta-ductal co-arctation of the aorta with multiple enlarged chest wall collaterals. The patient underwent a two-stage percutaneous procedure involving stent insertion and angioplasty up to 16 mm with significant improvement in exercise capacity and a modest reduction in blood pressure. PMID- 22665916 TI - Aggressiveness in different presentations of cluster headache: results from a controlled multicentric study. AB - BACKGROUND: The hypothalamus has been discussed as a pivotal structure for both cluster headache (CH) and aggressiveness, but little is known about the extent of self-reported aggressiveness in patients with CH. PATIENTS AND METHODS: Twenty six patients with chronic, 25 with active episodic and 22 with episodic CH outside the active period were examined interictally with a validated questionnaire quantifying factors of aggression and compared with 24 migraine patients and 31 headache-free volunteers. RESULTS: The ANOVA was significant for the subscale 'self-aggression/depression' (F(4, 123) = 5.771, p < 0.001) with significant differences between chronic and episodic CH and healthy volunteers. No significant changes were found for other subscales and the sum scale (F(4, 123) < 1.421, p > 0.230). Especially in the clinically most affected group of patients (chronic CH and active episodic CH), high levels of "self aggression/depression" correlate with higher prevalence of depressive symptoms and higher impairment measured on an emotional and functional level. DISCUSSION: Self-aggressive and depressive cognitions with highest scores in chronic CH seem to be reactive as they correlate with depressive symptoms and impairment. They should be considered as an important therapeutic target since they impair the patient's life significantly. PMID- 22665917 TI - MALDI-TOF mass spectrometry: transformative proteomics for clinical microbiology. PMID- 22665918 TI - Whole-blood thrombin generation monitored with a calibrated automated thrombogram based assay. AB - BACKGROUND: The calibrated automated thrombogram (CAT) assay in plasma is a versatile tool to investigate patients with hypo- or hypercoagulable phenotypes. The objective was to make this method applicable for whole blood measurements. METHODS: Thin-layer technology and the use of a rhodamine 110-based thrombin substrate appear to be essential for a reliable thrombin generation (TG) assay in whole blood. Using this knowledge we developed a whole blood CAT-based assay. RESULTS: We demonstrated that the whole blood CAT-based assay is a sensitive and rapid screening test to assess function of the hemostatic system under more nearly physiological conditions than the TG assay in plasma. Under conditions of low tissue factor concentration (0.5 pmol/L) and 50% diluted blood, the intraassay CV of the thrombogram parameters, endogenous thrombin potential and thrombin peak height, were 6.7% and 6.5%, respectively. The respective interassay CVs were 12% and 11%. The mean interindividual variation (SD) of 40 healthy volunteers was 633 (146) nmol . min/L for the endogenous thrombin potential and 128 (23) nmol/L for the thrombin peak. Surprisingly, erythrocytes contributed more than platelets to the procoagulant blood cell membranes necessary for optimal TG. Statistically significant (P < 0.001) and potentially clinically significant correlations were observed between circulating factor-VIII concentrations in blood of hemophilia A patients and endogenous thrombin potential (r = 0.62) and thrombin peak height (r = 0.58). CONCLUSIONS: We have developed a reliable method to measure TG in whole blood. The assay can be performed with a drop of blood and may provide a useful measurement of TG under more physiological conditions than plasma. PMID- 22665919 TI - More technology or less to promote wound healing? PMID- 22665920 TI - Outcomes of three years of teamwork on critical limb ischemia in patients with diabetes and foot lesions. AB - To evaluate the outcomes of a multidisciplinary team working on diabetic foot (DF) patients with critical limb ischemia (CLI) in a specialized center, the authors retrospectively traced all the patients admitted in their department in 3 consecutive years with a diagnosis of CLI. From January 2006 to December 2008, 245 consecutive DF patients with CLI according the TransAtlantic interSociety Consensus II criteria were included in the study. Treatment strategy was decided by a team of diabetologists, inteventional radiologists, and vascular surgeons. Technical and clinical success, mortality, and ulcer recurrence were evaluated at 6 months and at a mean follow-up of 19.5 +/- 13.4 months. Percutaneous transluminal angioplasty (PTA) was performed in 189 (77%) patients, whereas medical treatment, open surgical revascularization (OSR), and primary amputation were performed in 44 (18.3%), 11 (4.3%), and 1 (0.5%) patients, respectively. Revascularization was successful in 227/233 (97.4%) patients. At follow-up, the overall clinical success rate was 60.4%; it was significantly (P = .001) higher after revascularization (75.9%) compared with medical treatment (48.3%). During follow-up, surgical interventions in the foot were 1.5 +/- 0.4 in those treated with PTA, 1.6 +/- 0.5 in those treated with OSR, and 0.3 +/- 0.8 in those receiving medical therapy (P < .05 compared with the others). Ulcer recurrence occurred in 29 (11.8%) patients: 4 (1.6%) in PTA, 2 (0.8%) in OSR, and 23 (9.4%) in the medical therapy group (P < .05). Major amputation rate was 9.3%, being significantly (P = .04) lower after revascularization (5.2%) compared with medical therapy alone (13.8%). Cumulative mortality rate was 10.6%. In conclusion, this study confirms the positive role of a PTA-first approach for revascularizing the complex cases of DF with CLI in a teamwork management strategy. PMID- 22665922 TI - Dermal substitute template use in diabetic foot ulcers: case reports. AB - Diabetic foot ulcers are a source of significant morbidity. Maximizing limb salvage is an important long-term objective. The use of dermal substitutes to aid limb salvage and reduce amputation rates has been described recently in the literature. Dermal substitutes were initially described in burns and have been demonstrated to be useful adjuncts in the management of these wounds. In diabetic foot ulcer management, the outcomes of the use of the dermal substitutes are limited. The authors describe their experience of the use of INTEGRA(r), a collagen-glycosaminoglycan dermal substitute, in 2 patients who presented with diabetic foot ulcers with exposed tendons. PMID- 22665923 TI - Endovascular treatment is a hope for patient with Buerger's disease and foot ulcer: case report. AB - Scarce information exists regarding the usefulness of the endovascular approach in patients with thromboangiitis obliterans and critical ischemia. A 41-old-man diagnosed with Buerger's disease had rest pain and a severe ulceration on the big toe. He had been scheduled for a big toe amputation. Typical findings of Buerger's disease were found in the angiogram including below-the-knee involvement and corkscrew collateral arteries. Stenoses of the posterior tibial artery were angioplastied and the plantar artery was recanalized and angioplastied. Healing was achieved and the patient remains asymptomatic 21 months after the procedure. The outcome achieved in this case and recent series should encourage doctors dealing with this problem to attempt limb salvage by means of the endovascular approach. PMID- 22665924 TI - ADHD and mental health status in Brazilian school-age children. AB - OBJECTIVE: To assess the prevalence of ADHD, mental health status, and risk factors in a sample of Brazilian children. METHOD: Target sample consisted of all children from 5 to 13 years registered in the public elementary school. Children with ADHD were compared with those without ADHD for sociodemographic, risk factors, and Child Behavior Checklist (CBCL) symptom dimensions. Multivariate models estimated determinants of ADHD diagnosis. RESULTS: Of the target sample, consents and complete information were obtained from 1,830 children (91.8%). The prevalence rate of ADHD was 5.1% (95% confidence interval [CI] = [4.2, 6.2]). In contrast to controls, children with ADHD presented higher levels of symptoms in the CBCL dimensions. In multivariate analyses, the diagnosis of ADHD was significantly influenced by maternal educational status (p = .019), income class (p = .012), and prenatal exposure to tobacco (p = .032). CONCLUSION: Prevalence and demographic features of ADHD in Brazil are similar to what has been reported worldwide. PMID- 22665925 TI - Increase in lymphogranuloma venereum cases in South Florida. AB - The purpose of the study was to evaluate the clinic prevalence and clinical characteristics of patients with LGV since 2007 when active clinic surveillance started. We review all the reports of rectal Chlamydia trachomatis and LGV testing of those samples. Chlamydia trachomatis LGV DNA was detected by Nucleic Acid Amplification/ompA gene sequencing. Medical records of all patients with LGV were reviewed. Prevalence of rectal CT among tested individuals was relatively stable during the study period: 2007 (15%), 2008 (15%), 2009 (12%) and 2010 (14%). Eight cases of LGV were identified during the study period, one in 2009 and seven in 2010. All individuals were male and all except one had sex with only men. Most of them were also infected with HIV (62.5%). We concluded that this is the first report of LGV cases in South Florida and shows a rapid increase in the number of cases in the last year. PMID- 22665926 TI - Evaluation of the sensitivity of scout radiographs on unenhanced helical CT in identifying ureteric calculi: a large UK tertiary referral centre experience. AB - OBJECTIVE: Unenhanced helical CT for kidney, ureter and bladder (CT KUB) has become the standard investigation for renal colic. This study aims to determine the sensitivity of scout radiographs in detecting ureteric calculi using CT KUB as a standard reference. METHODS: A retrospective review of consecutive patients who presented with acute flank pain and were investigated using CT KUB. 201 patients with positive ureteric calculi were included. Two radiologists independently reviewed the scout radiographs with access to CT KUB images. Each observer recorded the presence or absence of calculi, location, size and mean Hounsfield units of each calculus. RESULTS: 203 ureteric calculi were analysed from 201 patients. The overall sensitivity of scout radiographs for Observer A was 42.3% and for Observer B 52.2%, with an interobserver reliability kappa-value of 0.78. The significance of mean Hounsfield units and size between two groups of patients with visible stones and those not visible were tested; the p-value for both variables was <0.0001, which is statistically significant. The study found that calculi in the upper ureter and larger than 4 mm are more likely to be seen on the scout radiograph. CONCLUSIONS: Usage of CT scout radiography should be encouraged and reported routinely in conjunction with CT KUB as a baseline for treatment follow-up. PMID- 22665927 TI - Positioning accuracy for lung stereotactic body radiotherapy patients determined by on-treatment cone-beam CT imaging. AB - Stereotactic body radiotherapy for early stage non-small cell lung cancer is an emerging treatment option in the UK. Since relatively few high-dose ablative fractions are delivered to a small target volume, the consequences of a geometric miss are potentially severe. This paper presents the results of treatment delivery set-up data collected using Elekta Synergy (Elekta, Crawley, UK) cone beam CT imaging for 17 patients immobilised using the Bodyfix system (Medical Intelligence, Schwabmuenchen, Germany). Images were acquired on the linear accelerator at initial patient treatment set-up, following any position correction adjustments, and post-treatment. These were matched to the localisation CT scan using the Elekta XVI software. In total, 71 fractions were analysed for patient set-up errors. The mean vector error at initial set-up was calculated as 5.3 +/- 2.7 mm, which was significantly reduced to 1.4 +/- 0.7 mm following image guided correction. Post-treatment the corresponding value was 2.1 +/- 1.2 mm. The use of the Bodyfix abdominal compression plate on 5 patients to reduce the range of tumour excursion during respiration produced mean longitudinal set-up corrections of -4.4 +/- 4.5 mm compared with -0.7 +/- 2.6 mm without compression for the remaining 12 patients. The use of abdominal compression led to a greater variation in set-up errors and a shift in the mean value. PMID- 22665928 TI - "Primum non nocere"--first, do no harm. PMID- 22665929 TI - Organising pneumonia as a late abnormality in influenza A (H1N1) virus infection. PMID- 22665931 TI - The thoracic anterior spinal cord adhesion syndrome. AB - OBJECTIVES: This study included a series of middle-aged male and female patients who presented with chronic anterior hemicord dysfunction progressing to paraplegia. Imaging of anterior thoracic cord displacement by either a dural adhesion or a dural defect with associated cord herniation is presented. METHODS: This is a retrospective review of cases referred to a tertiary neuroscience centre over a 19-year period. Imaging series were classified by two experienced neuroradiologists against several criteria and correlated with clinical examination and/or findings at surgery. RESULTS: 16 cases were available for full review. Nine were considered to represent adhesions (four confirmed surgically) and four to represent true herniation (three confirmed surgically). In the three remaining cases the diagnosis was radiologically uncertain. CONCLUSION: The authors propose "thoracic anterior spinal cord adhesion syndrome" as a novel term to describe this patient cohort and suggest appropriate clinicoradiological features for diagnosis. Several possible aetiologies are also suggested, with disc rupture and inflammation followed by disc resorption and dural pocket formation being a possible mechanism predisposing to herniation at the extreme end of a clinicopathological spectrum. PMID- 22665932 TI - Primary and secondary breast lymphoma: prevalence, clinical signs and radiological features. AB - OBJECTIVES: The purpose of this study was to determine the prevalence, clinical signs and radiological features of breast lymphoma. METHODS: This is a retrospective review of 36 patients with breast lymphoma (22 primary and 14 secondary). 35 patients were female and 1 was male; their median age was 65 years (range 24-88 years). In all patients, the diagnosis was confirmed histopathologically. RESULTS: The prevalence of breast lymphoma was 1.6% of all identified cases with non-Hodgkin lymphoma and 0.5% of cases with breast cancer. B-cell lymphoma was found in 94% and T-cell lymphoma in 6%. 96 lesions were identified (2.7 per patient). The mean size was 15.8 +/- 8.3 mm. The number of intramammary lesions was higher in secondary than in primary lymphoma. The size of the identified intramammary lesions was larger in primary than in secondary lymphoma. Clinically, 86% of the patients presented with solitary or multiple breast lumps. In 14%, breast involvement was diagnosed incidentally during staging examinations. CONCLUSION: On mammography, intramammary masses were the most commonly seen (27 patients, 82%). Architectural distortion occurred in three patients (9%). In three patients (9%), no abnormalities were found on mammography. On ultrasound, the identified lesions were homogeneously hypoechoic or heterogeneously mixed hypo- to hyperechoic. On MRI, the morphology of the lesions was variable. After intravenous administration of contrast medium, a marked inhomogeneous contrast enhancement was seen in most cases. On CT, most lesions presented as circumscribed round or oval masses with moderate or high enhancement. PMID- 22665933 TI - Dual actions of Meis1 inhibit erythroid progenitor development and sustain general hematopoietic cell proliferation. AB - Myeloid ecotropic viral integration site 1 (Meis1) forms a heterodimer with Pbx1 that augments Hox-dependent gene expression and is associated with leukemogenesis and HSC self-renewal. Here we identified 2 independent actions of Meis1 in hematopoietic development: one regulating cellular proliferation and the other involved in megakaryocyte lineage development. First, we found that endogenous Mesp1 indirectly induces Meis1 and Meis2 in endothelial cells derived from embryonic stem cells. Overexpression of Meis1 and Meis2 greatly enhanced the formation of hematopoietic colonies from embryonic stem cells, with the exception of erythroid colonies, by maintaining hematopoietic progenitor cells in a state of proliferation. Second, overexpression of Meis1 repressed the development of early erythroid progenitors, acting in vivo at the megakaryocyte-erythroid progenitor stage to skew development away from erythroid generation and toward megakaryocyte development. This previously unrecognized action of Meis1 may explain the embryonic lethality observed in Meis1(-/-) mice that arises from failure of lymphatic-venous separation and can result as a consequence of defective platelet generation. These results show that Meis1 exerts 2 independent functions, with its role in proliferation of hematopoietic progenitors acting earlier in development from its influence on the fate choice at the megakaryocyte erythroid progenitor between megakaryocytic and erythroid development. PMID- 22665934 TI - Mouse hematopoietic cell-targeted STAT3 deletion: stem/progenitor cell defects, mitochondrial dysfunction, ROS overproduction, and a rapid aging-like phenotype. AB - Nuclear transcription factor Stat3 is important for proper regulation of hematopoietic stem cell (HSC) and hematopoietic progenitor cell (HPC) proliferation, survival, and cytokine signaling responses. A new, noncanonical role for Stat3 in mitochondrial function has been discovered recently. However, there is little information on the role(s) of mitochondrial Stat3 in HSC/HPC function, especially potential effects of Stat3/mitochondrial dysregulation in human diseases. We investigated hematopoietic cell-targeted deletion of the STAT3 gene in HSCs/HPCs with a focus on mitochondrial function. We found that STAT3(-/ ) mice, which have a very shortened lifespan, dysfunctional/dysregulated mitochondrial function and excessive reactive oxygen species production in HSCs/HPCs that coincides with pronounced defects in function. These animals have a blood phenotype with similarities to premature aging and to human diseases of myelodysplastic syndrome and myeloproliferative neoplasms such as erythroid dysplasia, anemia, excessive myeloproliferation, and lymphomyeloid ratio shifts. We show herein that the lifespan of STAT3(-/-) animals is lengthened by treatment with a reactive oxygen species scavenger, which lessened the severity of the blood phenotype. These data suggest a need for more detailed studies of role(s) of Stat3 in HSC/HPC mitochondrial function in human diseases and raise the idea that mitochondrial Stat3 could be used as a potential therapeutic target. PMID- 22665935 TI - Calpain inhibition stabilizes the platelet proteome and reactivity in diabetes. AB - Platelets from patients with diabetes are hyperreactive and demonstrate increased adhesiveness, aggregation, degranulation, and thrombus formation, processes that contribute to the accelerated development of vascular disease. Part of the problem seems to be dysregulated platelet Ca(2+) signaling and the activation of calpains, which are Ca(2+)-activated proteases that result in the limited proteolysis of substrate proteins and subsequent alterations in signaling. In the present study, we report that the activation of MU- and m-calpain in patients with type 2 diabetes has profound effects on the platelet proteome and have identified septin-5 and the integrin-linked kinase (ILK) as novel calpain substrates. The calpain-dependent cleavage of septin-5 disturbed its association with syntaxin-4 and promoted the secretion of alpha-granule contents, including TGF-beta and CCL5. Calpain was also released by platelets and cleaved CCL5 to generate a variant with enhanced activity. Calpain activation also disrupted the ILK-PINCH-Parvin complex and altered platelet adhesion and spreading. In diabetic mice, calpain inhibition reversed the effects of diabetes on platelet protein cleavage, decreased circulating CCL5 levels, reduced platelet-leukocyte aggregate formation, and improved platelet function. The results of the present study indicate that diabetes-induced platelet dysfunction is mediated largely by calpain activation and suggest that calpain inhibition may be an effective way of preserving platelet function and eventually decelerating atherothrombosis development. PMID- 22665936 TI - High-content live-cell imaging assay used to establish mechanism of trastuzumab emtansine (T-DM1)--mediated inhibition of platelet production. AB - Proplatelet production represents a terminal stage of megakaryocyte development during which long, branching processes composed of platelet-sized swellings are extended and released into the surrounding culture. Whereas the cytoskeletal mechanics driving these transformations have been the focus of many studies, significant limitations in our ability to quantify the rate and extent of proplatelet production have restricted the field to qualitative analyses of a limited number of cells over short intervals. A novel high-content, quantitative, live-cell imaging assay using the IncuCyte system (Essen BioScience) was therefore developed to measure the rate and extent of megakaryocyte maturation and proplatelet production under live culture conditions for extended periods of time. As proof of concept, we used this system in the present study to establish a mechanism by which trastuzumab emtansine (T-DM1), an Ab-drug conjugate currently in clinical development for cancer, affects platelet production. High content analysis of primary cell cultures revealed that T-DM1 is taken up by mouse megakaryocytes, inhibits megakaryocyte differentiation, and disrupts proplatelet formation by inducing abnormal tubulin organization and suppressing microtubule dynamic instability. Defining the pathways by which therapeutics such as T-DM1 affect megakaryocyte differentiation and proplatelet production may yield strategies to manage drug-induced thrombocytopenias. PMID- 22665937 TI - Does size matter in platelet production? AB - Platelet (PLT) production represents the final stage of megakaryocyte (MK) development. During differentiation, bone marrow MKs extend and release long, branched proPLTs into sinusoidal blood vessels, which undergo repeated abscissions to yield circulating PLTs. Circular-prePLTs are dynamic intermediate structures in this sequence that have the capacity to reversibly convert into barbell-proPLTs and may be related to "young PLTs" and "large PLTs" of both inherited and acquired macrothrombocytopenias. Conversion is regulated by the diameter and thickness of the peripheral microtubule coil, and PLTs are capable of enlarging in culture to generate barbell-proPLTs that divide to yield 2 smaller PLT products. Because PLT number and size are inversely proportional, this raises the question: do macrothrombocytopenias represent a failure in the intermediate stages of PLT production? This review aims to bring together and contextualize our current understanding of terminal PLT production against the backdrop of human macrothrombocytopenias to establish how "large PLTs" observed in both conditions are similar, how they are different, and what they can teach us about PLT formation. A better understanding of the cytoskeletal mechanisms that regulate PLT formation and determine PLT size offers the promise of improved therapies for clinical disorders of PLT production and an important source of PLTs for infusion. PMID- 22665939 TI - Preterm babies have greater risk of severe psychiatric conditions as adults, study finds. PMID- 22665938 TI - A phase 1/2 study of carfilzomib in combination with lenalidomide and low-dose dexamethasone as a frontline treatment for multiple myeloma. AB - This phase 1/2 study in patients with newly diagnosed multiple myeloma (N = 53) assessed CRd--carfilzomib (20, 27, or 36 mg/m2, days 1, 2, 8, 9, 15, 16 and 1, 2, 15, 16 after cycle 8), lenalidomide (25 mg/d, days 1-21), and weekly dexamethasone (40/20 mg cycles 1-4/5+)--in 28-day cycles. After cycle 4, transplantation-eligible candidates underwent stem cell collection (SCC) then continued CRd with the option of transplantation. The maximum planned dose level (carfilzomib 36 mg/m2) was expanded in phase 2 (n = 36). Thirty-five patients underwent SCC, 7 proceeded to transplantation, and the remainder resumed CRd. Grade 3/4 toxicities included hypophosphatemia (25%), hyperglycemia (23%), anemia (21%), thrombocytopenia (17%), and neutropenia (17%); peripheral neuropathy was limited to grade 1/2 (23%). Most patients did not require dose modifications. After a median of 12 cycles (range, 1-25), 62% (N = 53) achieved at least near complete response (CR) and 42% stringent CR. Responses were rapid and improved during treatment. In 36 patients completing 8 or more cycles, 78% reached at least near CR and 61% stringent CR. With median follow-up of 13 months (range, 4 25 months), 24-month progression-free survival estimate was 92%. CRd was well tolerated with exceptional response rates. This study is registered at http://www.clinicaltrials.gov as NCT01029054. PMID- 22665940 TI - Signal modulation as a mechanism for handicap disposal. AB - Signal honesty may be compromised when heightened competition provides incentive for signal exaggeration. Some degree of honesty might be maintained by intrinsic handicap costs on signalling or through imposition of extrinsic costs, such as social punishment of low quality cheaters. Thus, theory predicts a delicate balance between signal enhancement and signal reliability that varies with degree of social competition, handicap cost, and social cost. We investigated whether male sexual signals of the electric fish Brachyhypopomus gauderio would become less reliable predictors of body length when competition provides incentives for males to boost electric signal amplitude. As expected, social competition under natural field conditions and in controlled lab experiments drove males to enhance their signals. However, signal enhancement improved the reliability of the information conveyed by the signal, as revealed in the tightening of the relationship between signal amplitude and body length. Signal augmentation in male B. gauderio was independent of body length, and thus appeared not to be curtailed through punishment of low quality (small) individuals. Rather, all individuals boosted their signals under high competition, but those whose signals were farthest from the predicted value under low competition boosted signal amplitude the most. By elimination, intrinsic handicap cost of signal production, rather than extrinsic social cost, appears to be the basis for the unexpected reinforcement of electric signal honesty under social competition. Signal modulation may provide its greatest advantage to the signaller as a mechanism for handicap disposal under low competition rather than as a mechanism for exaggeration of quality under high competition. PMID- 22665942 TI - Higher Education and Religious Liberalization among Young Adults. AB - Going to college has long been assumed to liberalize students' religious beliefs. Using longitudinal data from the National Survey of Youth and Religion, we compare change in the content of religious beliefs of those who do and do not attend college. We find that, in general, college students are no more likely to develop liberal religious beliefs than nonstudents. In some cases, collegians actually appear more likely to retain their initial beliefs. Change in religious beliefs appears instead to be more strongly associated with network effects. These findings indicate that college's effect on students' religious beliefs is both weak and fragmented, and suggest that the multiplicity of social worlds on college campuses may help to sustain religious beliefs as well as religious practice and commitment. PMID- 22665941 TI - Mixed land use and obesity: an empirical comparison of alternative land use measures and geographic scales. AB - Obesity is a growing epidemic in the United States. Walkable neighborhoods, characterized as having the 3Ds of walkability (population Density, land use Diversity, and pedestrian-friendly Design), have been identified as a potentially promising factor to prevent obesity for their residents. Past studies examining the relationship between obesity and walkability vary in geographic scales of neighborhood definitions and methods of measuring the 3Ds. To better understand potential influences of these sometimes arbitrary choices, we test how four types of alternative measures of land use diversity measured at three geographic scales relate to body mass index for 4960 Salt Lake County adults. Generalized estimation equation models demonstrate that optimal diversity measures differed by gender and geographic scale and that integrating walkability measures at different scales improved the overall performance of models. PMID- 22665943 TI - Electronically Rich N-Substituted Tetrahydroisoquinoline 3-Carboxylic Acid Esters: Concise Synthesis and Conformational Studies. AB - Recent work in our laboratory has shown that the highly substituted, electronically rich 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (THIQ3CA) scaffold is a key building block for a novel class of promising anticoagulants (Al-Horani et al. J. Med. Chem.2011, 54, 6125-6138). The synthesis of THIQ3CA analogs, especially containing specific, electronically rich substituents, has been a challenge and essentially no efficient methods have been reported in the literature. We describe three complementary, glycine donor-based strategies for high yielding synthesis of highly substituted, electronically rich THIQ3CA esters. Three glycine donors studied herein include hydantoin 1, (+/-)-Boc-alpha phosphonoglycine trimethyl ester 2 and (+/-)-Z-alpha-phosphonoglycine trimethyl ester 3. Although the synthesis of THIQ3CA analogs could be achieved using either of the three, an optimal, high yielding approach for the desired THIQ3CA esters was best achieved using 3 in three mild, efficient steps. Using this approach, a focused library of advanced N-arylacyl, N-arylalkyl, and bis-THIQ3CA analogs was synthesized. Variable temperature and solvent-dependent NMR chemical shift studies indicated the presence of two major conformational rotamers in 3:1 proportion for N-arylacyl-THIQ3CA analogs, which were separated by a high kinetic barrier of ~17 kcal/mol. In contrast, N-arylalkyl and bis-THIQ3CA variants displayed no rotamerism, which implicates restricted rotation around the amide bond as the origin for high-barrier conformational interconversion. This phenomenon is of major significance because structure-based drug design typically utilizes only one conformation. Overall, the work presents fundamental studies on the synthesis and conformational properties of highly substituted, electronically rich THIQ3CA analogs. PMID- 22665944 TI - Uricases as therapeutic agents to treat refractory gout: Current states and future directions. AB - Treatment of refractory gout remains a challenge on drug development. While pegloticase, a recombinant mammalian uricase modified with monomethoxyl poly(ethylene glycol) (mPEG) is effective in treating refractory gout, after continued treatment for three months biweekly at a therapeutic dose of 0.14 mg/kg body weight, it elicits an immune response against mPEG in nearly 20% of patients. For continued treatment of refractory gout PEGylated uricases at monthly therapeutic doses below 4 MUg/kg body weight have promise. To formulate uricases to achieve monthly therapeutic regimens requires pharmacodynamics simulation and experimentation including: (a) molecular engineering of uricases based on rational design and evolution biotechnology in combination to improve their inherent catalytic efficiency, thermostability and selectivity for urate over xanthine and; (b) optimization of the number and distribution of accessible reactive amino acid residues in native uricases for site-specific PEGylation with PEG derivatives with lower of immunogenicity than mPEG to retain activity, minimize immunogenicity and enhance the pharmacokinetics of the PEGylated uricase. These issues are briefly reviewed as a means to stimulate the development of safer uricase formulations for continued treatment of refractory gout. PMID- 22665945 TI - Activity Settings and Daily Routines in Preschool Classrooms: Diverse Experiences in Early Learning Settings for Low-Income Children. AB - This paper examines activity settings and daily classroom routines experienced by 3- and 4-year-old low-income children in public center-based preschool programs, private center-based programs, and family child care homes. Two daily routine profiles were identified using a time-sampling coding procedure: a High Free Choice pattern in which children spent a majority of their day engaged in child directed free-choice activity settings combined with relatively low amounts of teacher-directed activity, and a Structured-Balanced pattern in which children spent relatively equal proportions of their day engaged in child-directed free choice activity settings and teacher-directed small- and whole-group activities. Daily routine profiles were associated with program type and curriculum use but not with measures of process quality. Children in Structured-Balanced classrooms had more opportunities to engage in language and literacy and math activities, whereas children in High Free-Choice classrooms had more opportunities for gross motor and fantasy play. Being in a Structured-Balanced classroom was associated with children's language scores but profiles were not associated with measures of children's math reasoning or socio-emotional behavior. Consideration of teachers' structuring of daily routines represents a valuable way to understand nuances in the provision of learning experiences for young children in the context of current views about developmentally appropriate practice and school readiness. PMID- 22665946 TI - Relational Aggression in Middle Childhood: Predictors and Adolescent Outcomes. AB - This study examined gender differences in the level and developmental course of relational aggression in middle childhood, as well as early predictors and outcomes of relational aggression, after controlling for concurrent physical aggression. Relational (RAgg) and Physical aggression (PAgg) scores for 558 boys and 545 girls at ages 8-11 in the NICHD Study of Early Child Care and Youth Development (SECCYD) were created by combining the highest rating for each item across mother and teacher reports. Longitudinal analyses were conducted using Latent Curve Models of RAgg with PAgg as a time-varying covariate, with all parameters allowed to vary by gender. Boys and girls had different growth parameters of RAgg. Girls' RAgg intercept was higher and the slope was not different from zero; boys' RAgg intercept was lower and the slope declined. Mother-child conflict in early childhood predicted RAgg intercept for both boys and girls, but maternal harsh control and sensitivity were also uniquely predictive for girls, whereas center care was uniquely predictive for boys. RAgg intercept predicted adolescent self-reports of depression for girls and delinquency and risk-taking for both boys and girls; the magnitude of the association with risk-taking was significantly greater for boys. PMID- 22665947 TI - Epigenetic regulation of cytokine production in human amnion and villous placenta. AB - The mechanisms of human preterm labour appear inextricably linked to cytokine biosynthesis by gestational tissues. In turn, cytokine production by gestational tissues has been shown to be regulated by epigenetic mechanisms. In this paper, we demonstrate that cytokine production in gestational tissues is regulated epigenetically in a tissue-specific manner. Furthermore, we show that treatment with a histone deacetylation inhibitor can partially abrogate LPS-stimulated TNFalpha production in villous placenta but not amnion. LPS treatment significantly (P < 0.05) increased the production of IL-1beta (~10-34-fold), TNFalpha (~23->100-fold) and IL10 (~6-10-fold) after 24 h of treatment in villous explants, as expected. There were no significant LPS effects on IL1Ra production. AZA treatment did not have any significant effect on any cytokines' production tested either alone or in combination with LPS. Interestingly, however, the stimulatory effects of LPS on TNFalpha production were partially mitigated (P < 0.05) by TSA treatment in villous explants. We suggest caution in the consideration of histone deacetylation inhibitors in pregnancy due to the different responses in gestational tissues. PMID- 22665948 TI - Nutrition, inflammation, and infectious disease. PMID- 22665950 TI - Disruption of the ECM33 gene in Candida albicans prevents biofilm formation, engineered human oral mucosa tissue damage and gingival cell necrosis/apoptosis. AB - In this study we demonstrated that DeltaCaecm33 double mutant showed reduced biofilm formation and causes less damage to gingival mucosa tissues. This was confirmed by the reduced level of necrotic cells and Bax/Bcl2 gene expression as apoptotic markers. In contrast, parental and Caecm33 mutant strains decreased basement membrane protein production (laminin 5 and type IV collagen). We thus propose that ECM33 gene/protein represents a novel target for the prevention and treatment of infections caused by Candida. PMID- 22665949 TI - Eicosanoids and respiratory viral infection: coordinators of inflammation and potential therapeutic targets. AB - Viruses are frequent causes of respiratory infection, and viral respiratory infections are significant causes of hospitalization, morbidity, and sometimes mortality in a variety of patient populations. Lung inflammation induced by infection with common respiratory pathogens such as influenza and respiratory syncytial virus is accompanied by increased lung production of prostaglandins and leukotrienes, lipid mediators with a wide range of effects on host immune function. Deficiency or pharmacologic inhibition of prostaglandin and leukotriene production often results in a dampened inflammatory response to acute infection with a respiratory virus. These mediators may, therefore, serve as appealing therapeutic targets for disease caused by respiratory viral infection. PMID- 22665951 TI - Anti-inflammatory and antinociceptive effects of salbutamol on acute and chronic models of inflammation in rats: involvement of an antioxidant mechanism. AB - The possible role of beta-2 adrenergic receptors in modulation of inflammatory and nociceptive conditions suggests that the beta-2 adrenergic receptor agonist, salbutamol, may have beneficial anti-inflammatory and analgesic effects. Therefore, in this study, we induced inflammatory and nociceptive responses with carrageenan-induced paw edema or cotton-pellet-induced granuloma models, both of which result in oxidative stress. We hypothesized that salbutamol would prevent inflammatory and nociceptive responses by stimulating beta-2 adrenergic receptors and the prevention of generation of ROS during the acute inflammation process in rats. Both doses of salbutamol used in the study (1 and 2 mg/kg) effectively blocked the acute inflammation and inflammatory nociception induced by carrageenan. In the cotton-pellet-induced granuloma test, both doses of salbutamol also significantly decreased the weight of granuloma tissue on the cotton pellets when compared to the control. Anti-inflammatory and analgesic effects of salbutamol were found to be comparable with those of indomethacin. Salbutamol decreased myeloperoxidase (MPO) activity and lipid peroxidation (LPO) level and increased the activity of superoxide dismutase (SOD) and level of glutathione (GSH) during the acute phase of inflammation. In conclusion, salbutamol can decrease acute and chronic inflammation, possibly through the stimulation of beta-2 adrenergic receptors. This anti-inflammatory effect may be of significance in asthma treatment, where inflammation also takes part in the etiopathology. This study reveals that salbutamol has significant antioxidative effects, which at least partially explain its anti-inflammatory capabilities. These findings presented here may also shed light on the roles of beta-2 adrenergic receptors in inflammatory and hyperalgesic conditions. PMID- 22665952 TI - Usefulness of faecal calprotectin measurement in children with various types of inflammatory bowel disease. AB - INTRODUCTION: The aim of the study was to assess the usefulness of the FC measurement in children with various types of IBD and relation to the disease activity. PATIENTS AND METHODS: 91 patients (49 boys: 53.85% and 42 girls: 46.15%, mean age: 13.38 years, range 6-18 years) were included in the analysis. Patients were divided into the groups: B1-24 children with CD, B2-16 patients with UC, and a group comprising 31 children with other types of colitis; the control group (K) comprised 20 healthy children. FC was assayed by ELISA method, using Phical test (Calpro). RESULTS: The mean faecal calprotectin concentrations were higher in children with CD and UC as compared to healthy controls, patients with eosinophilic, lymphocytic, and nonspecific colitis. A positive correlation was observed between FC concentrations and the disease activity (the PCDAI scale, the Truelove-Witts Scale, and the endoscopic Rachmilewitz Index). CONCLUSION: It seems that the FC concentrations can be a useful, safe, and noninvasive test in children suspected for IBD, since FC concentration is higher in children with CD and UC than in patients with other inflammatory diseases. PMID- 22665953 TI - Lipopolysaccharides: from Erinyes to Charites. AB - Following the discovery of endotoxins by Richard Pfeiffer, such bacterial product was associated to many severe disorders produced by an overwhelming inflammatory response and often resulting in endotoxic shock and multiple organ failure. However, recent clinical and basic sciences investigations claimed some beneficial roles of typical as well as atypical endotoxins. The aim of this paper is to focus on recent data supporting a beneficial activity of both typical and atypical endotoxins. Such novel perspective looks promising for development of new drugs for prevention and therapy of several human diseases. PMID- 22665954 TI - Cyclooxygenase inhibition in sepsis: is there life after death? AB - Prostaglandins are important mediators and modulators of the inflammatory response to infection. The prostaglandins participate in the pathogenesis of hemodynamic collapse, organ failure, and overwhelming inflammation that characterize severe sepsis and shock. In light of this, cyclooxygenase (COX) inhibiting pharmacological agents have been extensively studied for their capacity to ameliorate the aberrant physiological and immune responses during severe sepsis. Animal models of sepsis, using the systemic administration of pathogen-associated molecular patterns (PAMPs) or live pathogens, have been used to examine the effectiveness of COX inhibition as a treatment for severe sepsis. These studies have largely shown beneficial effects on mortality. However, human studies have failed to show clinical utility of COX inhibitor treatment in severely septic patients. Why this approach "worked" in animals but not in humans might reflect differences in the controlled nature of animal investigations compared to human studies. This paper contrasts the impact of COX inhibitors on mortality in animal models of sepsis and human studies of sepsis and examines potential reasons for differences between these two settings. PMID- 22665955 TI - Patterns of prescription medication diversion among drug dealers. AB - This research examined the following questions: (1) how do drug dealers acquire their inventories of prescription medications? and (2) which types of prescription medications do dealers most commonly sell? Data are drawn from a National Institute on Drug Abuse-funded research study that examined prescription drug diversion and abuse in South Florida. In-depth semi-structured interviews (n = 50) were conducted with an ethnically diverse sample of prescription drug dealers from a variety of milieus to assess patterns of diversion. Audiotapes of the interviews were transcribed, coded, and thematically analysed using the NVivo 8 software program. Dealers relied on a wide array of diversion methods including visiting multiple pain clinics, working with pharmacy employees to steal medications from pharmacies, and purchasing medications from indigent patients. The type of medication most commonly sold by dealers was prescription opioid analgesics, and to a lesser extent benzodiazepines such as alprazolam. These findings inform public health policy makers, criminal justice officials, the pharmaceutical industry and government regulatory agencies in their efforts to reduce the availability of diverted prescription drugs in the illicit market. Specifically, these data support the need for statewide prescription drug monitoring programs and increased training for healthcare workers who have access to controlled medications. PMID- 22665956 TI - Variability of Accessory Pathway Refractory Periods: What Should be the Criteria for Ablation in Asymptomatic WPW. PMID- 22665957 TI - A linear ablating system in the left and right atrium: feasibility, catheter performance and clinical results. AB - INTRODUCTION: We describe the use of a ablating system to compartmentalise and regionally isolate the atria in paroxysmal and persistent atrial fibrillation (AF). METHODS: 40 patients were studied, 25 paroxysmal AF and 14 persistent AF. One patient enrolled was later found to be in left atrial flutter and was excluded. The Cardima Revelation(r) TX catheter system with Intellitemp(r) Radiofrequency (RF) energy control device and a Medtronic Atakar(r) RF generator were used to place wide area circumferential ablations to achieve conduction block into the left and right sided pulmonary veins. Roof lines and mitral isthmus lines were also performed. In patients with persistent AF and in repeat procedures, right atrial compartmentalisation was performed with an anterior superior vena cava (SVC) to inferior vena cava (IVC) line and a septal SVC to IVC line. RESULTS: At 6 months, 18 of the 39 patients were asymptomatic, 10 had improved symptoms and 22 were in sinus rhythm. In the paroxysmal group, 11 were asymptomatic, 7 had improved symptoms and 16 (64%) were in sinus rhythm. In the persistent group, 7 were asymptomatic, 3 had improved symptoms and 6 (43%) were in sinus rhythm. The total group AF burden was 37.8 +/- 5.4 hrs pre-procedure and 23.1 +/- 5.1 hrs at 6 months post procedure. Mean temperature, impedance and power recorded at each pole demonstrated effective power delivery at all poles. No catheter charring was observed, complication rates were comparable to standard AF ablation technique. CONCLUSION: Linear ablation in the left and right atria to mimic Cox's Maze is feasible and safe using this ablating system. PMID- 22665958 TI - Is the measurement of accessory pathway refractory period reproducible? AB - INTRODUCTION: Short accessory pathway (AP) effective refractory period (ERP) is one of the risk factors in Wolff-Parkinson-White syndrome (WPW). The purpose of study was to evaluate the reproducibility of APERP measurement during a same electrophysiological study (EPS). METHODS: EPS consisted of 2 APERP measurements performed prospectively in 77 patients for a WPW in control state (CS) at a cycle length of 400 ms (n=76) and after isoproterenol (n=56). RESULTS: In CS, 18 patients (24 %) had the same APERP at both measurements; 41 (54.6 %) had differences from 10 to 40 ms, 17 (22.4 %) had differences > 40 ms. Among 45 patients with initial APERP > 240 ms, 7 had an APERP <= 240 ms at 2nd study. Among 31 patients with initial APERP <= 240 ms, 5 had an APERP > 240 ms at 2nd study. Pearson's product-moment correlation was 0.75. After isoproterenol, 5 patients (9 %) had the same APERPs; 37 (66 %) had differences from 10 to 40 ms and 14 had differences > 40 ms. Among 38 patients with initial APERP > 200 ms, 12 had an AP ERP <= 200 ms at 2nd study. Among 18 patients with initial APERP <= 200 ms, 10 had still APERP <= 200 ms at 2nd study. Pearson's product-moment correlation was 0.54. CONCLUSION: There are important variations of APERPs during EPS mainly after isoproterenol infusion. Therefore the values of APERPs should be interpreted cautiously. PMID- 22665959 TI - The downside of right ventricular apical pacing. AB - The right ventricular (RV) apex has been the standard pacing site since the development of implantable pacemaker technology. Although RV pacing was initially only utilized for the treatment of severe bradyarrhythmias usually due to complete heart block, today the indications for and implantation of RV pacing devices is dramatically larger. Recently, the adverse effects of chronic RV apical pacing have been described including an increased risk of heart failure and death. This review details the detrimental effects of RV apical pacing and their shared hemodynamic pathophysiology. In particular, the role of RV apical pacing induced ventricular dyssynchrony is highlighted with a specific focus on differential outcome based upon QRS morphology at implant. PMID- 22665960 TI - Biventricular / left ventricular pacing in hypertrophic obstructive cardiomyopathy: an overview. AB - Hypertrophic cardiomyopathy (HCM) is an autosomal dominant inherited genetic disease characterized by compensatory pathological left ventricle (LV) hypertrophy due to sarcomere dysfunction. In an important proportion of patients with HCM, the site and extent of cardiac hypertrophy results in severe obstruction to LV outflow tract (LVOT), contributing to disabling symptoms and increasing the risk of sudden cardiac death (SCD). In patients with progressive and/or refractory symptoms despite optimal pharmacological treatment, invasive therapies that diminish or abolish LVOT obstruction relieve heart failure-related symptoms, improve quality of life and could be associated with long-term survival similar to that observed in the general population. The gold standard in this respect is surgical septal myectomy, which might be supplementary associated with a reduction in SCD. Percutaneous techniques, particularly alcohol septal ablation (ASA) and more recently radiofrequency (RF) septal ablation, can achieve LVOT gradient reduction and symptomatic benefit in a large proportion of HOCM patients at the cost of a supposedly limited septal myocardial necrosis and a 10-20% risk of chronic atrioventricular block. After an initial period of enthusiasm, standard DDD pacing failed to show in randomized trials significant LVOT gradient reductions and objective improvement in exercise capacity. However, case reports and recent small pilot studies suggested that atrial synchronous LV or biventricular (biV) pacing significantly reduce LVOT obstruction and improve symptoms (acutely as well as long-term) in a large proportion of severely symptomatic HOCM patients not suitable to other gradient reduction therapies. Moreover, biV/LV pacing in HOCM seems to be associated with significant LV reverse remodelling. PMID- 22665961 TI - Successful Ablation of Antero-septal Accessory Pathway in the Non-Coronary Cusp in a Child. AB - A 15-year-old boy with Wolff-Parkinson-White syndrome underwent an electrophysiology study for symptoms of palpitations and persistence of pre excitation during peak exercise. He was detected to have right antero-septal accessory pathway with relatively long effective refractory period and no inducible tachycardia. He had only transient normalization with cryoablation. Eight months later, he presented again with two episodes of seizures with preceding palpitations. Neurology evaluation was unremarkable with a normal electroencephalogram. In view of his symptoms in association with evidence of pre excitation, he underwent a second electrophysiology study with ablation. Cryoablation in the anterior septum again achieved only transient normalization. Mapping in the non-coronary cusp identified an earliest accessory pathway potential. RF ablation was performed in the non-coronary cusp with immediate normalization of his electrocardiogram. At 6 month follow-up, he continues to have no pre-excitation on his EKG. Ablation of the anteroseptal accessory pathway in the non-coronary cusp can be safely performed in patients' refractory to conventional ablation sites and techniques. PMID- 22665962 TI - Indigenous telemedicine. AB - We are describing a simple and innovative way of documenting tachycardia. This patient came with video recording of neck pulsation done with the help of mobile phone camera. No other documentation of this tachycardia was available as patient was living in a remote area away from even basic health facilities. PMID- 22665963 TI - Antegrade or retrograde accessory pathway conduction: who dies first? AB - A 36 year-old man with Wolff Parkinson White syndrome due to a left-sided accessory pathway (AP) was referred for catheter ablation. Whether abolition of antegrade and retrograde AP conduction during ablation therapy occurs simultaneously, is unclear. At the ablation procedure, radiofrequency delivery resulted in loss of preexcitation followed by a short run of orthodromic tachycardia with eccentric atrial activation, demonstrating persistence of retrograde conduction over the AP after abolition of its antegrade conduction. During continued radiofrequency delivery at the same position, the fifth non preexcitated beat failed to conduct retrogradely and the tachycardia ended. In this case, antegrade AP conduction was abolished earlier than retrograde conduction. PMID- 22665964 TI - Simultaneous Inference For The Mean Function Based on Dense Functional Data. AB - A polynomial spline estimator is proposed for the mean function of dense functional data together with a simultaneous confidence band which is asymptotically correct. In addition, the spline estimator and its accompanying confidence band enjoy oracle efficiency in the sense that they are asymptotically the same as if all random trajectories are observed entirely and without errors. The confidence band is also extended to the difference of mean functions of two populations of functional data. Simulation experiments provide strong evidence that corroborates the asymptotic theory while computing is efficient. The confidence band procedure is illustrated by analyzing the near infrared spectroscopy data. PMID- 22665965 TI - Endoscopic Evaluation of Symptomatic Patients following Bariatric Surgery: A Literature Review. AB - Obesity is an epidemic in our society, and rates continue to rise, along with comorbid conditions associated with obesity. Unfortunately, obesity remains refractory to behavioral and drug therapy but has shown response to bariatric surgery. Not only can long-term weight loss be achieved, but a majority of patients have also shown improvement of the comorbid conditions associated with obesity. A rise in the use of surgical therapy for management of obesity presents a challenge with an increased number of patients with problems after bariatric surgery. It is important to be familiar with symptoms following bariatric surgery, such as nausea/vomiting, abdominal pain, dysphagia, and upper gastrointestinal bleeding and to utilize appropriate available tests for upper gastrointestinal tract pathology in the postoperative period. PMID- 22665966 TI - Rinsability of orthophthalaldehyde from endoscopes. AB - Orthophthalaldehyde high level disinfectants are contraindicated for use with urological instruments such as cystoscopes due to anaphylaxis-like allergic reactions during surveillance of bladder cancer patients. Allergic reactions and mucosal injuries have also been reported following colonoscopy, laryngoscopy, and transesophageal echocardiography with devices disinfected using orthophthalaldehyde. Possibly these endoscopes were not adequately rinsed after disinfection by orthophthalaldehyde. We examined this possibility by means of a zone-of-inhibition test, and also a test to extract residues of orthophthalaldehyde with acetonitrile, from sections of endoscope insertion tube materials, to measure the presence of alkaline glutaraldehyde, or glutaraldehyde plus 20% w/w isopropanol, or ortho-phthalaldehyde that remained on the endoscope materials after exposure to these disinfectants followed by a series of rinses in water, or by aeration overnight. Zones of any size indicated the disinfectant had not been rinsed away from the endoscope material. There were no zones of inhibition surrounding endoscope materials soaked in glutaraldehyde or glutaraldehyde plus isopropanol after three serial water rinses according to manufacturers' rinsing directions. The endoscope material soaked in orthophthalaldehyde produced zones of inhibition even after fifteen serial rinses with water. Orthophthalaldehyde was extracted from the rinsed endoscope material by acetonitrile. These data, and other information, indicate that the high level disinfectant orthophthalaldehyde, also known as 1,2-benzene dialdehyde, cannot be rinsed away from flexible endoscope material with any practical number of rinses with water, or by drying overnight. PMID- 22665968 TI - Strain-dependent production of interleukin-17/interferon-gamma and matrix remodeling-associated genes in experimental Candida albicans keratitis. AB - PURPOSE: The aim of this study was to investigate the role of genetic background in determining the development or prognosis of experimental fungal keratitis by comparing the disease courses and related molecules of experimental Candida albicans in two common mouse strains. METHODS: After intrastromal inoculation of 1 * 10(5)C. albicans blastospores into corneas of Balb/c and C57BL/6 mice, all mice developed typical keratitis. The disease was monitored using a slit lamp microscope and scored for comparison of symptoms. At desired time points, blood was collected and corneal homogenates were prepared for enzyme-linked immunosorbent assay measurement of interferon (IFN)gamma or interleukin (IL)17. Other corneas were processed for histological evaluation, pathogen load measurement, or total RNA extraction, the last of which was subjected to reverse transcription in conjunction with real-time PCR to measure genes of interest in terms of collagens, matrix metalloproteinases (MMPs), and the tissue inhibitors of MMPs (TIMPs). RESULTS: The infected corneas from the two strains presented different manifestations. Corneal transparency was less affected in Balb/c mice than in C57BL/6 mice, and Balb/c corneas contained fewer pathogens than C57BL/6 corneas during the measured period (10 days). In both strains, keratitis started to resolve around days 7-10, but C57BL/6 mice healed slower than Balb/c mice as indicated by disease presentation, histology, and pathogen burden assay. By day 7 post infection, pseudohyphae were rare but cellular infiltration remained intensive in both strains. The surface of the Balb/c corneas remained relatively intact and smooth, and C57BL/6 corneal lesions produced open erosion areas. Perforation was never seen in the current study setting. In both sera and corneas, IL17 expression increased earlier than IFNgamma, and C57BL/6 mice produced higher IL17 levels and lower IFNgamma levels than Balb/c mice. Compared with C57BL/6 mice, Balb/c corneas produced more MMP-2, Col3a1, and Col4a1, and less or equivalent TIMP-2 at all detected time points. They also produced more MMP-13, less MMP-8, MMP-9, and TIMP-1 at day 3 post infection, but less MMP-13, basically equivalent MMP-8, and more MMP-9 at later time points. CONCLUSIONS: The disease course of experimental C. albicans keratitis depends on the genetic background of the host animals. The balance between IL17 and IFNgamma, as well as among the common injury- and wound healing-related proteins, may contribute to the pathogenesis of C. albicans keratitis. This study suggests that great variance of disease presentation should be expected for human subjects with Candida keratitis. PMID- 22665967 TI - Gene expression changes within Muller glial cells in retinitis pigmentosa. AB - PURPOSE: Retinitis pigmentosa (RP) is a progressive retinal degeneration in which the retina loses nearly all of its photoreceptor cells and undergoes major structural changes. Little is known regarding the role the resident glia, the Muller glia, play in the progression of the disease. In this article, we define gene expression changes in Muller glial cells (MGCs) from two different mouse models of RP, the retinal degeneration 1 (rd1) and rhodopsin knockout (Rhod-ko) models. The RNA repertoire of single MGCs was comprehensively profiled, and a comparison was made between MGCs from wild-type (WT) and mutant retinas. Two time points were chosen for analysis, one at the peak of rod photoreceptor death and one during the period of cone photoreceptor death. METHODS: Retinas were dissociated, and single MGCs were chosen under a dissecting microscope using a micropipette. Single cell cDNAs were generated and genome-wide profiles were obtained by hybridization to Affymetrix arrays. A comparison was made among all samples to discover the changes in gene expression during the periods of rod and cone photoreceptor death. RESULTS: MGCs respond to retinal degeneration by undergoing gliosis, a process marked by the upregulation of glial fibrillary acidic protein (Gfap). Many additional transcripts were found to change. These can be placed into functional clusters, such as retinal remodeling, stress response, and immune-related response. CONCLUSIONS: A high degree of heterogeneity among the individual cells was observed, possibly due to their different spatial proximities to dying cells and/or inherent heterogeneity among MGCs. PMID- 22665969 TI - Identification of recurrent and novel mutations in TULP1 in Pakistani families with early-onset retinitis pigmentosa. AB - PURPOSE: To identify the genetic defects underlying retinitis pigmentosa (RP) in Pakistani families. METHODS: Genome-wide high-density single-nucleotide polymorphism microarray analysis was performed using the DNA of nine affected individuals from two large families with multiple consanguineous marriages. Data were analyzed to identify homozygous regions that are shared by affected sibs in each family. Sanger sequencing was performed for genes previously implicated in autosomal recessive RP and allied retinal dystrophies that resided in the identified homozygous regions. Probands from both families underwent fundus examination and electroretinogram measurements. RESULTS: The tubby-like protein 1 gene (TULP1) was present in the largest homozygous region in both families. Sequence analysis identified a previously reported mutation (c.1138A>G; p.Thr380Ala) in one family and a novel pathogenic variant (c.1445G>A; p.Arg482Gln) in the other family. Both variants were found to be present in a homozygous state in all affected individuals, were heterozygous present in the unaffected parents, and heterozygous present or absent in normal individuals. Affected individuals of both families showed an early-onset form of RP. CONCLUSIONS: Homozygosity mapping, combined with candidate-gene analysis, successfully identified genetic defects in TULP1 in two large Pakistani families with early-onset retinitis pigmentosa. PMID- 22665970 TI - Downregulation of transforming growth factor-beta type II receptor prohibit epithelial-to-mesenchymal transition in lens epithelium. AB - PURPOSE: Transforming growth factor-beta (TGF-beta) is considered to be essential to induce epithelial-to-mesenchymal transition (EMT) which plays central roles in wound healing in ocular fibrotic complication. The present study investigates whether small interference RNAs (siRNAs) targeting the type II receptor of TGF beta (TbetaRII) could be used to minimize the TGF-beta action. METHODS: TGF-beta receptor type II (TbetaRII) specific siRNAs designed from the Nakamura human gene sequence were used to transfect the cultured lens epithelial cells (LECs). The optimal transfection of scramble siRNA-Cy3 labeled duplexes in cultured LECs were examined by laser scanning confocal microscope and flow cytometry. TbetaRII protein expression and transcript levels were analyzed by immunofluorescence, western blotting, and real time PCR, respectively. Western blotting was performed to examine protein expression of fibronectin and alpha-smooth muscle actin (alpha SMA). Scratch assay was used to determine cell migration. Cell morphology was observed after transfection by inverted microscope. RESULTS: The optimal transfection rate of scramble siRNA-Cy3 labeled duplexes was efficient in that nearly to 50% in cultured LECs. TbetaRII specific siRNAs significantly reduced the receptor transcript and protein expression in cultured LECs. The gene knockdown inhibited LECs transdifferentiation, as it abrogated the expression of fibronectin and alpha-SMA, and retarded cell migration on the scratch assay. In addition, after transfection with TbetaRII specific siRNA, the cultured LECs did not show fibroblast-like shape which was one of the feature signs of EMT. Wound scratch assays indicated that the number of cultured LECs migrated into the wounded area was significantly lower in TbetaRII specific siRNA treated group (12.8 +/- 3.27/7.85 mm(2)), compared with normal (57.8 +/- 3.06/7.85 mm(2)) and scrambled RNA transfected group (50.8 +/- 3.64/7.85 mm(2); p<0.0001). CONCLUSIONS: Our results provided additional evidence to support that TGF-beta pathway was involved in the development of EMT of human posterior capsule opacification, while how TbetaRII was involved should be further investigated. PMID- 22665971 TI - Glutathione S-transferases polymorphisms confer susceptibility to senile cortical cataract in the Han Chinese population. AB - PURPOSE: The aim of this study was to examine whether glutathione S-transferase (GST) polymorphisms were associated with a susceptibility to age-related cortical cataract (cortical ARC) in the Han Chinese population. METHODS: Glutathione S transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1) gene polymorphisms were genotyped in 422 Han Chinese patients with age-related cortical cataract, and in 312 age, sex, and ethnically matched healthy controls, using a multiplex polymerase chain reaction. RESULTS: The results showed that the GSTM1 positive genotype had an increased risk of developing cortical ARC (p=0.0002, odds ratio [OR] 1.74, 95% CI 1.30 to 2.34). There was a statistically significant association between the GSTM1 positive genotype and the risk of cataract development in both female and male groups (p=0.026, OR 1.58, 95% CI 1.05 to 2.36; p=0. 002, OR 1.97, 95% CI 1.27 to 3.04, respectively). A combination of GSTM1 positive and GSTT1 null genotypes was associated with the risk of developing age-related cortical cataract (p=0.002, OR 2.19, 95% CI 1.33 to 3.60). The results revealed that the GSTM1 positive genotype was significantly higher in the smoker patients group as compared to the non-smoker patients group (p=0. 016, OR 1.62, 95% CI 1.09 to 2.39). Logistic regression analysis revealed that smoking may be a risk factor for the development of ARC (r=0.120, p=0.013). CONCLUSIONS: Our study suggests that the GSTM1 positive genotype and a combination of GSTM1 positive and GSTT1 null genotypes may be associated with a susceptibility to age-related cortical cataract in the Han Chinese population. The current study indicates that smoking may be an important factor in the development of cortical ARC. PMID- 22665972 TI - A nonsense mutation in S-antigen (p.Glu306*) causes Oguchi disease. AB - PURPOSE: Genetic studies were performed to identify the causative mutation in a 15-year-old girl diagnosed with congenital stationary night blindness (CSNB) presenting Mizuo-Nakamura phenomenon, a typical Oguchi disease symptom. The patient also had dural sinus thrombosis (DST), thrombocytopenia, and systemic lupus erythematosus (SLE). METHODS: Mutation analysis was done by sequencing two candidate genes, S-antigen (SAG; arrestin 1), associated with Oguchi type 1, and rhodopsin kinase (GRK1), associated with Oguchi type 2. In addition, the C677T variation in the methylenetetrahydrofolate reductase (MTHFR) gene was also screened in the family, to determine its probable association with hyperhomocysteinemia in the patient. RESULTS: Sequencing of the SAG and GRK1 resulted in identifying a novel homozygous nonsense mutation (c.916G>T; p.Glu306*) in SAG, which in unaffected siblings either was present in a heterozygous state or absent. The C677T heterozygous allele in the MTHFR gene was found to be associated with hyperhomocysteinemia in the patient and other family members. CONCLUSIONS: This is the first report of Oguchi type 1 in a Pakistani patient due to a nonsense mutation (c.916G>T; p.Glu306*) in SAG. The neurologic and hematological abnormalities likely are not associated with the SAG variant. PMID- 22665974 TI - Characterization of cultivated murine lacrimal gland epithelial cells. AB - PURPOSE: To date, mouse lacrimal gland epithelial cells have been cultured successfully but only in cases involving newborn mouse lacrimal glands. In this work, we attempted to cultivate and characterize adult mouse lacrimal gland epithelial cells. METHODS: Lacrimal glands were removed from newborn mice (C57B/6) and isolated lacrimal gland epithelial cells were seeded onto tissue culture treated or low adherent culture dishes in Cnt-07 culture medium with or without cholera toxin. Cultivated cells were characterized by immunostaining with pan-cytokeratin, alpha-smooth muscle actin, and lactoferrin antibodies. Lacrimal gland cells from 7-week-old green fluorescent protein (GFP) and non-GFP (C57B/6) mice were mixed and seeded onto uncoated dishes to assess sphere-forming efficiency. Cells were also seeded onto 3T3 cell feeder layers to assess colony forming efficiency. RESULTS: Lacrimal gland epithelial cells were selectively cultured with cholera toxin, and cell type was verified by pan-cytokeratin and alpha-smooth muscle actin immunostaining. Sphere formation from single cells of adult mice was observed using specific medium and low adherent culture dishes. These cells could also undergo colony formation on 3T3 feeder cells. CONCLUSIONS: Adult mouse lacrimal gland epithelial cells were successfully cultivated in cholera toxin-containing medium, and were observed to form spheres from single cells. PMID- 22665973 TI - Deletion of HIF-1alpha partially rescues the abnormal hyaloid vascular system in Cited2 conditional knockout mouse eyes. AB - PURPOSE: Cited2 (CBP/p300-interacting transactivators with glutamic acid (E) and aspartic acid (D)-rich tail 2) is a member of a new family of transcriptional modulators. Cited2 null embryos exhibit hyaloid hypercellularity consisting of aberrant vasculature in the eye. The purpose of the study is to address whether abnormal lenticular development is a primary defect of Cited2 deletion and whether deletion of hypoxia inducible factor (HIF)-1alpha or an HIF-1alpha target gene, vascular endothelial growth factor (VEGF), could rescue abnormal hyaloid vascular system (HVS) in Cited2 deficient adult eyes. METHODS: Le-Cre specific Cited2 knockout (Cited2(CKO)) mice with or without deletion of HIF-1alpha or VEGF were generated by standard Cre-Lox methods. Eyes collected from six-eight weeks old mice were characterized by Real Time PCR and immunohistological staining. RESULTS: Cited2(CKO) mice had smaller lenses, abnormal lens stalk formation, and failed regression of the HVS in the adult eye. The eye phenotype had features similar to persistent hyperplastic primary vitreous (PHPV), a human congenital eye disorder leading to abnormal lenticular development. Deletion of HIF-1alpha or VEGF in Cited2 knockout eyes partially rescued the abnormal HVS but had no effect on the smaller lens and abnormal lens stalk differentiation. Intravitreal injection of Topotecan (TPT), a compound that inhibits HIF-1alpha expression, partially eliminated HVS defects in Cited2(CKO) lenses. CONCLUSIONS: Abnormal HVS is a primary defect in Cited2 knockout mice, resulting in part from dysregulated functions of HIF-1 and VEGF. The Cited2(CKO) mouse line could be used as a novel disease model for PHPV and as an in vivo model for testing potential HIF-1 inhibitors. PMID- 22665975 TI - Ala344Pro mutation in the FGFR2 gene and related clinical findings in one Chinese family with Crouzon syndrome. AB - PURPOSE: The purpose of this study was to investigate the fibroblast growth factor receptor 2 (FGFR2) gene in three Chinese patients with Crouzon syndrome and to characterize the related clinical features. METHODS: A single family underwent complete ophthalmic examinations, and three patients were diagnosed with Crouzon syndrome. Genomic DNA was extracted from leukocytes of peripheral blood collected from members of the family as well as from 100 unrelated control subjects from the same population. Exons 8 and 10 of FGFR 2 were amplified by polymerase chain reaction (PCR) and directly sequenced. We performed ophthalmic examinations, including best-corrected visual acuity, slit-lamp examination, fundus examination, Pentacam, Goldmann perimetry, and computed tomography (CT) of the skull. RESULTS: The three patients were affected with shallow orbits and ocular proptosis, accompanied by mid-face hypoplasia and craniosynostosis, but had clinically normal hands and feet. A heterozygous FGFR2 missense mutation c.1030G>C (Ala344Pro) in exon 10 was identified in the affected individuals, but not in any of the unaffected family members or the normal controls. The mutation we identified has not previously been reported, either in China or abroad. CONCLUSIONS: Although FGFR2 mutations and polymorphisms have been reported in various ethnic groups, especially in the area of osteology, we report, for the first time, the identification of one new FGFR2 gene mutation in Chinese patients with Crouzon syndrome. PMID- 22665976 TI - A novel T->G splice site mutation of CRYBA1/A3 associated with autosomal dominant nuclear cataracts in a Chinese family. AB - PURPOSE: The purpose of this study was to identify the disease-causing mutation and the molecular phenotype that are responsible for the presence of an autosomal dominant congenital nuclear cataract disease in a Chinese family. METHODS: The family history and clinical data were recorded. The patients were given a physical examination and their blood samples were collected for DNA extraction. Direct sequencing was used to detect the mutation. Transcription analysis of the mutant crystallin, beta A1 (CRYBA1/A3) gene was performed to verify whether the defective mutation had influenced the splice of the mature mRNA. RESULTS: The phenotype of the congenital cataract in the family was identified as a nuclear cataract type, by using slit-lamp photography. Direct sequencing revealed a novel mutation IVS3+2 T->G in CRYBA1/A3. This mutation co-segregated with all affected individuals in the family, but was not found in unaffected family members nor in the 100 unrelated controls. Transcription analysis of the mutant CRYBA1/A3 gene indicated that this mutation had influenced the splice of the mature mRNA. CONCLUSIONS: Our study identified a novel splice site mutation in CRYBA1/A3. This mutation was responsible for aberrant splicing of the mature mRNA and had caused the congenital nuclear cataracts in the family. This is the first report relating an IVS3+2 T->G mutation of CRYBA1/A3 to congenital cataracts. PMID- 22665977 TI - Ex vivo expanded SSEA-4+ human limbal stromal cells are multipotent and do not express other embryonic stem cell markers. AB - PURPOSE: The presence of multipotent human limbal stromal cells resembling mesenchymal stromal cells (MSC) provides new insights to the characteristic of these cells and its therapeutic potential. However, little is known about the expression of stage-specific embryonic antigen 4 (SSEA-4) and the embryonic stem cell (ESC)-like properties of these cells. We studied the expression of SSEA-4 surface protein and the various ESC and MSC markers in the ex vivo cultured limbal stromal cells. The phenotypes and multipotent differentiation potential of these cells were also evaluated. METHODS: Limbal stromal cells were derived from corneoscleral rims. The SSEA-4(+) and SSEA-4(-) limbal stromal cells were sorted by fluorescence-activated cells sorting (FACS). Isolated cells were expanded and reanalyzed for their expression of SSEA-4. Expression of MSC and ESC markers on these cells were also analyzed by FACS. In addition, expression of limbal epithelial and corneal stromal proteins such as ATP-binding cassette sub-family G member 2 (ABCG2), tumour protein p63 (p63), paired box 6 (Pax6), cytokeratin 3 (AE5), cytokeratin 10, and keratocan sulfate were evaluated either by immunofluorecence staining or reverse transcription polymerase chain reaction. Appropriate induction medium was used to differentiate these cells into adipocytes, osteocytes, and chondrocytes. RESULTS: Expanded limbal stromal cells expressed the majority of mesenchymal markers. These cells were negative for ABCG2, p63, Pax6, AE-5, and keratocan sulfate. After passaged, a subpopulation of these cells showed low expression of SSEA-4 but were negative for other important ESC surface markers such as Tra-1-60, Tra-1-81, and transcription factors like octamer-binding transcription factor 4 (Oct4), SRY(sex determining region Y)-box 2 (Sox2), and Nanog. Early passaged cells when induced were able to differentiate into adipocytes, osteocytes and chondrocytes. CONCLUSIONS: The expanded limbal stromal cells showed features of multipotent MSC. Our study confirmed the expression of SSEA-4 by a subpopulation of cultured limbal stromal cells. However, despite the expression of SSEA-4, these cells did not express any other markers of ESC. Therefore, we conclude that the cells did not show properties of ESC. PMID- 22665978 TI - Novel image analysis approach quantifies morphological characteristics of 3D breast culture acini with varying metastatic potentials. AB - Prognosis of breast cancer is primarily predicted by the histological grading of the tumor, where pathologists manually evaluate microscopic characteristics of the tissue. This labor intensive process suffers from intra- and inter-observer variations; thus, computer-aided systems that accomplish this assessment automatically are in high demand. We address this by developing an image analysis framework for the automated grading of breast cancer in in vitro three dimensional breast epithelial acini through the characterization of acinar structure morphology. A set of statistically significant features for the characterization of acini morphology are exploited for the automated grading of six (MCF10 series) cell line cultures mimicking three grades of breast cancer along the metastatic cascade. In addition to capturing both expected and visually differentiable changes, we quantify subtle differences that pose a challenge to assess through microscopic inspection. Our method achieves 89.0% accuracy in grading the acinar structures as nonmalignant, noninvasive carcinoma, and invasive carcinoma grades. We further demonstrate that the proposed methodology can be successfully applied for the grading of in vivo tissue samples albeit with additional constraints. These results indicate that the proposed features can be used to describe the relationship between the acini morphology and cellular function along the metastatic cascade. PMID- 22665979 TI - A novel model of atherosclerosis in rabbits using injury to arterial walls induced by ferric chloride as evaluated by optical coherence tomography as well as intravascular ultrasound and histology. AB - This study aim was to develop a new model of atherosclerosis by FeCl(3)-induced injury to right common carotid arteries (CCAs) of rabbits. Right CCAs were induced in male New Zealand White rabbits (n = 15) by combination of a cholesterol-rich diet and FeCl(3)-induced injury to arterial walls. The right and left CCAs were evaluated by histology and in vivo intravascular ultrasound (IVUS) and optical coherence tomography (OCT) examinations of 24 hours (n = 3), 8 weeks (n = 6), and 12 weeks (n = 6) after injury. Each right CCA of the rabbits showed extensive white-yellow plaques. At eight and 12 weeks after injury, IVUS, OCT, and histological findings demonstrated that the right CCAs had evident eccentric plaques. Six plaques (50%) with evident positive remodeling were observed. Marked progression was clearly observed in the same plaque at 12 weeks after injury when it underwent repeat OCT and IVUS. We demonstrated, for the first time, a novel model of atherosclerosis induced by FeCl(3). The model is simple, fast, inexpensive, and reproducible and has a high success rate. The eccentric plaques and remodeling of plaques were common in this model. We successfully carried out IVUS and OCT examinations twice in the same lesion within a relatively long period of time. PMID- 22665980 TI - Transfer of bone-marrow-derived mesenchymal stem cells influences vascular remodeling and calcification after balloon injury in hyperlipidemic rats. AB - Bone-marrow-derived mesenchymal stem cells (BM-MSCs) were found to markedly increase atherosclerotic lesion size. The aim of this paper was to investigate whether BM-MSCs contribute to vascular remodeling and calcification after balloon injury in hyperlipidemic rats. Labeled BM-MSCs were found in the lesion of hyperlipidemic rats after balloon injury. Comparing injury group, transferred BM MSCs significantly triggered vascular negative remodeling, characterized by the changes of remodeling index (0.628 +/- 0.0293 versus 0.544 +/- 0.0217), neointimal area (0.078 +/- 0.015 mm(2) versus 0.098 +/- 0.019 mm(2)), PCNA index (23.91 +/- 6.59% versus 43.11 +/- 5.31%), and percentage of stenosis (18.20 +/- 1.09% versus 30.58 +/- 1.21%). Apparent vascular calcification was detected in medial layers at 6 weeks after balloon angioplasty, which may be associated with upregulation of bone morphogenetic protein-2 (BMP-2). Our data indicated that unselected BM-MSCs transfer may induce vascular remodeling and calcification after balloon injury in hyperlipidemic rats. PMID- 22665981 TI - Cytokines and VEGF induction in orthodontic movement in animal models. AB - Orthodontics is a branch of dentistry that aims at the resolution of dental malocclusions. The specialist carries out the treatment using intraoral or extraoral orthodontic appliances that require forces of a given load level to obtain a tooth movement in a certain direction in dental arches. Orthodontic tooth movement is dependent on efficient remodeling of periodontal ligament and alveolar bone, correlated with several biological and mechanical responses of the tissues surrounding the teeth. A periodontal ligament placed under pressure will result in bone resorption whereas a periodontal ligament under tension results in bone formation. In the primary stage of the application of orthodontic forces, an acute inflammation occurs in periodontium. Several proinflammatory cytokines are produced by immune-competent cells migrating by means of dilated capillaries. In this paper we summarize, also through the utilization of animal models, the role of some of these molecules, namely, interleukin-1beta and vascular endothelial growth factor, that are some proliferation markers of osteoclasts and osteoblasts, and the macrophage colony stimulating factor. PMID- 22665982 TI - Difference between Pb and Cd accumulation in 19 elite maize inbred lines and application prospects. AB - In the last two decades, the accumulation of heavy metal in crop grains has become the study hotspot. In this study, 19 representative elite maize inbred lines and 3 hybrid varieties were investigated at the seedling stage, which can accumulate Pb and Cd in the stems and leaves, respectively. The results demonstrated that significant differences are among inbred lines for accumulation of heavy metals, implying that the Cd accumulation is significant correlation between the male parents and their hybrids and some inbred lines have been selected for cross-breeding with low Pb or Cd accumulation, such as S37, 9782, and ES40; Moreover, some inbred lines could be suitable for phytoremediation species for soil bioremediation with high levels of Pb and Cd accumulation, including 178, R08, 48-2, and Mo17ht. PMID- 22665983 TI - Pharmacokinetic models for FcRn-mediated IgG disposition. AB - The objectives were to review available PK models for saturable FcRn-mediated IgG disposition, and to explore an alternative semimechanistic model. Most available empirical and mechanistic PK models assumed equal IgG concentrations in plasma and endosome in addition to other model-specific assumptions. These might have led to inappropriate parameter estimates and model interpretations. Some physiologically based PK (PBPK) models included FcRn-mediated IgG recycling. The nature of PBPK models requires borrowing parameter values from literature, and subtle differences in the assumptions may render dramatic changes in parameter estimates related to the IgG recycling kinetics. These models might have been unnecessarily complicated to address FcRn saturation and nonlinear IgG PK especially in the IVIG setting. A simple semimechanistic PK model (cutoff model) was developed that assumed a constant endogenous IgG production rate and a saturable FcRn-binding capacity. The FcRn-binding capacity was defined as MAX, and IgG concentrations exceeding MAX in endosome resulted in lysosomal degradation. The model parameters were estimated using simulated data from previously published models. The cutoff model adequately described the rat and mouse IgG PK data simulated from published models and allowed reasonable estimation of endogenous IgG turnover rates. PMID- 22665984 TI - Advances in arbovirus surveillance, detection and diagnosis. PMID- 22665985 TI - Biofuel manufacturing from woody biomass: effects of sieve size used in biomass size reduction. AB - Size reduction is the first step for manufacturing biofuels from woody biomass. It is usually performed using milling machines and the particle size is controlled by the size of the sieve installed on a milling machine. There are reported studies about the effects of sieve size on energy consumption in milling of woody biomass. These studies show that energy consumption increased dramatically as sieve size became smaller. However, in these studies, the sugar yield (proportional to biofuel yield) in hydrolysis of the milled woody biomass was not measured. The lack of comprehensive studies about the effects of sieve size on energy consumption in biomass milling and sugar yield in hydrolysis process makes it difficult to decide which sieve size should be selected in order to minimize the energy consumption in size reduction and maximize the sugar yield in hydrolysis. The purpose of this paper is to fill this gap in the literature. In this paper, knife milling of poplar wood was conducted using sieves of three sizes (1, 2, and 4 mm). Results show that, as sieve size increased, energy consumption in knife milling decreased and sugar yield in hydrolysis increased in the tested range of particle sizes. PMID- 22665986 TI - Posterior circulation stroke: animal models and mechanism of disease. AB - Posterior circulation stroke refers to the vascular occlusion or bleeding, arising from the vertebrobasilar vasculature of the brain. Clinical studies show that individuals who experience posterior circulation stroke will develop significant brain injury, neurologic dysfunction, or death. Yet the therapeutic needs of this patient subpopulation remain largely unknown. Thus understanding the causative factors and the pathogenesis of brain damage is important, if posterior circulation stroke is to be prevented or treated. Appropriate animal models are necessary to achieve this understanding. This paper critically integrates the neurovascular and pathophysiological features gleaned from posterior circulation stroke animal models into clinical correlations. PMID- 22665987 TI - Evaluation of distinct freezing methods and cryoprotectants for human amniotic fluid stem cells cryopreservation. AB - Amniotic fluid (AF) was described as a potential source of mesenchymal stem cells (MSCs) for biomedicine purposes. Therefore, evaluation of alternative cryoprotectants and freezing protocols capable to maintain the viability and stemness of these cells after cooling is still needed. AF stem cells (AFSCs) were tested for different freezing methods and cryoprotectants. Cell viability, gene expression, surface markers, and plasticity were evaluated after thawing. AFSCs expressed undifferentiated genes Oct4 and Nanog; presented typical markers (CD29, CD44, CD90, and CD105) and were able to differentiate into mesenchymal lineages. All tested cryoprotectants preserved the features of AFSCs however, variations in cell viability were observed. In this concern, dimethyl sulfoxide (Me(2)SO) showed the best results. The freezing protocols tested did not promote significant changes in the AFSCs viability. Time programmed and nonprogrammed freezing methods could be used for successful AFSCs cryopreservation for 6 months. Although tested cryoprotectants maintained undifferentiated gene expression, typical markers, and plasticity of AFSCs, only Me(2)SO and glycerol presented workable viability ratios. PMID- 22665988 TI - Therapeutic strategies based on polymeric microparticles. AB - The development of the field of materials science, the ability to perform multidisciplinary scientific work, and the need for novel administration technologies that maximize therapeutic effects and minimize adverse reactions to readily available drugs have led to the development of delivery systems based on microencapsulation, which has taken one step closer to the target of personalized medicine. Drug delivery systems based on polymeric microparticles are generating a strong impact on preclinical and clinical drug development and have reached a broad development in different fields supporting a critical role in the near future of medical practice. This paper presents the foundations of polymeric microparticles based on their formulation, mechanisms of drug release and some of their innovative therapeutic strategies to board multiple diseases. PMID- 22665989 TI - Animal models of glaucoma. AB - Glaucoma is a heterogeneous group of disorders that progressively lead to blindness due to loss of retinal ganglion cells and damage to the optic nerve. It is a leading cause of blindness and visual impairment worldwide. Although research in the field of glaucoma is substantial, the pathophysiologic mechanisms causing the disease are not completely understood. A wide variety of animal models have been used to study glaucoma. These include monkeys, dogs, cats, rodents, and several other species. Although these models have provided valuable information about the disease, there is still no ideal model for studying glaucoma due to its complexity. In this paper we present a summary of most of the animal models that have been developed and used for the study of the different types of glaucoma, the strengths and limitations associated with each species use, and some potential criteria to develop a suitable model. PMID- 22665990 TI - Dextran sodium sulphate colitis mouse model: traps and tricks. AB - Inflammatory bowel disease (IBD) is a complex multifactorial disease of unknown etiology. Thus, dozens of different animal models of IBD have been developed in past decades. Animal models of IBD are valuable and indispensable tools that provide a wide range of options for investigating involvement of various factors into the pathogenesis of IBD and to evaluate different therapeutic options. However, the dextran sulphate sodium (DSS-) induced colitis model has some advantages when compared to other animal models of colitis. It is well appreciated and widely used model of inflammatory bowel disease because of its simplicity. It has many similarities to human IBD, which are mentioned in the paper. In spite of its simplicity and wide applicability, there are also traps that need to be taken into account when using DSS model. As demonstrated in the present paper, various factors may affect susceptibility to DSS-induced lesions and modify results. PMID- 22665992 TI - Investigating potential mechanisms of obesity by metabolomics. AB - Obesity is a serious health problem with an increased risk of several common diseases including diabetes, cardiovascular disease, and cancer. Metabolomics is an emerging analytical technique for systemic determination of metabolite profiles, which is useful for understanding the biochemical changes in obesity or related diseases both in individual organs and at the organism level. Increasingly, this technology has been applied to the study of obesity, complementing transcriptomics and/or proteomics analyses. Indeed, the alterations of metabolites in biofluids/tissues are direct indicators of variations in physiology or pathology. In this paper, we will examine the obesity-related alterations in significant metabolites that have been identified by metabolomics as well as their metabolic pathway associations. Issues concerning the screening of biologically significant metabolites related to obesity will also be discussed. PMID- 22665991 TI - Soluble host defense lectins in innate immunity to influenza virus. AB - Host defenses against viral infections depend on a complex interplay of innate (nonspecific) and adaptive (specific) components. In the early stages of infection, innate mechanisms represent the main line of host defense, acting to limit the spread of virus in host tissues prior to the induction of the adaptive immune response. Serum and lung fluids contain a range of lectins capable of recognizing and destroying influenza A viruses (IAV). Herein, we review the mechanisms by which soluble endogenous lectins mediate anti-IAV activity, including their role in modulating IAV-induced inflammation and disease and their potential as prophylactic and/or therapeutic treatments during severe IAV-induced disease. PMID- 22665993 TI - Biochemical and molecular analysis of some commercial samples of chilli peppers from Mexico. AB - The genus Capsicum provides antioxidant compounds, such as phenolics and carotenoids, into the diet. In Mexico, there is a wide diversity of species and varieties of chilli peppers, a fruit which has local cultural and gastronomic importance. In the present study, the relationship of the carotenoid and phenolic profiles with the RAPD fingerprint of three different commercial cultivars of chilli peppers of seven regions of Mexico was investigated. Through RAPD, the species of chilli were differentiated by means of different primers (OPE-18, MFG 17, MFG-18, C51, and C52). The genetic distance found with OPE 18 was in the order of 2.6. The observed differences were maintained when the chromatographic profile of carotenoids, and the molecular markers were analyzed, which suggest a close relationship between carotenoids and the genetic profile. While the chromatographic profile of phenols and the molecular markers were unable to differentiate between genotypes of chilli peppers. In addition, by using infrared spectroscopy and statistical PCA, differences explained by geographic origin were found. Thus, this method could be an alternative for identification of chilli species with respect to their geographic origin. PMID- 22665995 TI - Role of BiPAP applied through endotracheal tube in unconscious patients suffering from acute exacerbation of COPD: a pilot study. AB - BACKGROUND AND OBJECTIVES: Mechanical ventilation is the recommended treatment in unconscious patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) and hypercapenic respiratory failure. But, in resource-poor countries, many of these patients are not able to afford this treatment due to financial constraints. The main aim of this study was to evaluate the usefulness, safety and cost-effectiveness of bilevel positive airway pressure (BiPAP) applied via endotracheal tube in such patients. METHODS: Twenty patients with acute exacerbation of COPD and altered sensorium, who were unable to afford ventilatory support, were intubated and BiPAP therapy was provided to these patients through the endotracheal tube. The outcome of these patients was studied. RESULTS: The BiPAP success rate and hospital mortality were 85% (17/20) and 15% (3/20) respectively. BiPAP failure was associated with high sequential organ failure assessment (SOFA) score at the time of admission (P = 0.002). Improvement in Glasgow coma scale (GCS) score (P < 0.001), pH (P = 0.001), PaCO(2) (partial pressure of carbon dioxide) (P < 0.001), respiratory rate (P < 0.001), and SOFA score (P = 0.001) was observed among the responders following 2 hours of therapy. Only one of the responders developed aspiration pneumonitis, as a complication. The daily cost of BiPAP therapy was 8.75 times lower than the average cost of mechanical ventilation. CONCLUSION: This pilot study reveals that this treatment modality could be a safe, cost-effective and efficacious method of treatment in unconscious patients with acute exacerbation of COPD. PMID- 22665994 TI - Exercise prescription for hospitalized people with chronic obstructive pulmonary disease and comorbidities: a synthesis of systematic reviews. AB - INTRODUCTION: The prescription of physical activity for hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) can be complicated by the presence of comorbidities. The current research aimed to synthesize the relevant literature on the benefits of exercise for people with multimorbidities who experience an AECOPD, and ask: What are the parameters and outcomes of exercise in AECOPD and in conditions that are common comorbidities as reported by systematic reviews (SRs)? METHODS: An SR was performed using the Cochrane Collaboration protocol. Nine electronic databases were searched up to July 2011. Articles were included if they (1) described participants with AECOPD, chronic obstructive pulmonary disease (COPD), or one of eleven common comorbidities, (2) were an SR, (3) examined aerobic training (AT), resistance training (RT), balance training (BT), or a combination thereof, (4) included at least one outcome of fitness, and (5) compared exercise training versus control/sham. RESULTS: This synthesis examined 58 SRs of exercise training in people with AECOPD, COPD, or eleven chronic conditions commonly associated with COPD. Meta-analyses of endurance (aerobic or exercise capacity, 6-minute walk distance--6MWD) were shown to significantly improve in most conditions (except osteoarthritis, osteoporosis, and depression), whereas strength was shown to improve in five of the 13 conditions searched: COPD, older adults, heart failure, ischemic heart disease, and diabetes. Several studies of different conditions also reported improvements in quality of life, function, and control or prevention outcomes. Meta-analyses also demonstrate that exercise training decreases the risk of mortality in older adults, and those with COPD or ischemic heart disease. The most common types of training were AT and RT. BT and functional training were commonly applied in older adults. The quality of the SRs for most conditions was moderate to excellent (>65%) as evaluated by AMSTAR scores. CONCLUSION: In summary, this synthesis showed evidence of significant benefits from exercise training in AECOPD, COPD, and conditions that are common comorbidities. A broader approach to exercise and activity prescription in pulmonary rehabilitation may induce therapeutic benefits to ameliorate clinical sequelae associated with AECOPD and comorbidities such as the inclusion of BT and functional training. PMID- 22665996 TI - Cortical mapping with navigated transcranial magnetic stimulation in low-grade glioma surgery. AB - Transcranial magnetic stimulation (TMS) is a promising method for both investigation and therapeutic treatment of psychiatric and neurologic disorders and, more recently, for brain mapping. This study describes the application of navigated TMS for motor cortex mapping in patients with a brain tumor located close to the precentral gyrus. MATERIALS AND METHODS: In this prospective study, six patients with low-grade gliomas in or near the precentral gyrus underwent TMS, and their motor responses were correlated to locations in the cortex around the lesion, generating a functional map overlaid on three-dimensional magnetic resonance imaging (MRI) scans of the brain. To determine the accuracy of this new method, we compared TMS mapping with the gold standard mapping with direct cortical electrical stimulation in surgery. The same navigation system and TMS generated map were used during the surgical resection procedure. RESULTS: The motor cortex could be clearly mapped using both methods. The locations corresponding to the hand and forearm, found during intraoperative mapping, showed a close spatial relationship to the homotopic areas identified by TMS mapping. The mean distance between TMS and direct cortical electrical stimulation (DES) was 4.16 +/- 1.02 mm (range: 2.56-5.27 mm). CONCLUSION: Preoperative mapping of the motor cortex with navigated TMS prior to brain tumor resection is a useful presurgical planning tool with good accuracy. PMID- 22665998 TI - Effect of rehabilitation on a patient suffering from a tuberculous brain abscess with Gerstmann's syndrome: case report. AB - There are few reports in the literature of tuberculous brain abscess. Tuberculous brain abscess usually occurs in an immunocompromised host. Almost all previously documented cases have involved acquired immune deficiency syndrome. We encountered a 53-year-old right-handed immunocompetent male who was initially suspected of having a cerebrovascular accident due to acute-onset right hemiparesis and paresthesia. A tentative diagnosis of brain tumor versus brain abscess was made on imaging studies. The patient was finally diagnosed with a tuberculous brain abscess based upon deterioration on imaging and a positive tuberculosis culture. The tuberculous brain abscess was located in the left parietal lobe, which resulted in Gerstmann's syndrome and right-sided apraxia. Stereotactic surgery was performed. He was also given antituberculosis chemotherapy and comprehensive rehabilitation. Considerable improvement was noted after rehabilitation. The patient even returned to a normal life and work. Our case demonstrates that an aggressive intensive inpatient rehabilitation program combined with stereotactic surgery and effective antituberculosis therapy play an important role in improving the outcome for patients with tuberculous brain abscess, Gerstmann's syndrome, and right-sided apraxia. PMID- 22665997 TI - Optimal treatment of social phobia: systematic review and meta-analysis. AB - This article proposes a number of recommendations for the treatment of generalized social phobia, based on a systematic literature review and meta analysis. An optimal treatment regimen would include a combination of medication and psychotherapy, along with an assertive clinical management program. For medications, selective serotonin reuptake inhibitors and dual serotonin norepinephrine reuptake inhibitors are first-line choices based on their efficacy and tolerability profiles. The nonselective monoamine oxidase inhibitor, phenelzine, may be more potent than these two drug classes, but because of its food and drug interaction liabilities, its use should be restricted to patients not responding to selective serotonin reuptake inhibitors or serotonin norepinephrine reuptake inhibitors. There are other medication classes with demonstrated efficacy in social phobia (benzodiazepines, antipsychotics, alpha-2 delta ligands), but due to limited published clinical trial data and the potential for dependence and withdrawal issues with benzodiazepines, it is unclear how best to incorporate these drugs into treatment regimens. There are very few clinical trials on the use of combined medications. Cognitive behavior therapy appears to be more effective than other evidence-based psychological techniques, and its effects appear to be more enduring than those of pharmacotherapy. There is some evidence, albeit limited to certain drug classes, that the combination of medication and cognitive behavior therapy may be more effective than either strategy used alone. Generalized social phobia is a chronic disorder, and many patients will require long-term support and treatment. PMID- 22666000 TI - Alveolar soft part sarcoma: a single-center 26-patient case series and review of the literature. AB - Background. Alveolar soft part sarcoma (ASPS) is a rare tumor, and little information is available regarding its clinical features and appropriate treatments. Methods. A retrospective review of 26 consecutive ASPS patients (12 male, 14 female; mean age of 27 years) treated at our institution over 30 years (mean followup; 71 months) was performed. Results. The primary tumor developed in the lower extremity (12), trunk (8), and upper extremity (6), with an average size of 7.2 cm (range, 2-14 cm). The AJCC stage at presentation was IIA (7), III (3), and IV (16). Surgical excision was performed in 20 patients (R0 18, R1 plus radiotherapy 2) without local recurrence. Six patients (stage IIA 3/7, stage III 3/3) later developed metastases after an average period of 28.7 months. The median survival of the 26 patients was 90 months, with overall 5/10-year survival rates of 64%/48%. AJCC stage and tumor size were significant prognostic factors. Significant palliation and slowing of metastasis progression were achieved with gamma knife radiotherapy. Nine patients receiving chemotherapy showed no objective response. Conclusions. ASPS is indolent but has a high propensity for metastasis. Early diagnosis and complete excision of the small primary tumor are essential in the treatment of ASPS. PMID- 22666001 TI - Resonant frequency characteristics of a SAW device attached to resonating micropillars. AB - Recently we reported experimental and simulation results on an increase in resonance frequency of a SAW resonator caused by mass loading of micropillars made of SU-8, attached normal to the surface of the resonator. We concluded that SAW resonator and the SU-8 micropillars in unison form a system of coupled resonators. We have now extended this work and performed a finite element method simulation to study the resonance frequency characteristics of the SAW-based coupled resonator. In this paper we report the effect of the resonance frequency of the micropillars on the resonance frequency of the system of coupled resonators, and observe the coupling of micropillar resonance and the propagating SAW as described in the well known Dybwad system of coupled resonators. PMID- 22665999 TI - The molecular biology of soft-tissue sarcomas and current trends in therapy. AB - Basic research in sarcoma models has been fundamental in the discovery of scientific milestones leading to a better understanding of the molecular biology of cancer. Yet, clinical research in sarcoma has lagged behind other cancers because of the multiple clinical and pathological entities that characterize sarcomas and their rarity. Sarcomas encompass a very heterogeneous group of tumors with diverse pathological and clinical overlapping characteristics. Molecular testing has been fundamental in the identification and better definition of more specific entities among this vast array of malignancies. A group of sarcomas are distinguished by specific molecular aberrations such as somatic mutations, intergene deletions, gene amplifications, reciprocal translocations, and complex karyotypes. These and other discoveries have led to a better understanding of the growth signals and the molecular pathways involved in the development of these tumors. These findings are leading to treatment strategies currently under intense investigation. Disruption of the growth signals is being targeted with antagonistic antibodies, tyrosine kinase inhibitors, and inhibitors of several downstream molecules in diverse molecular pathways. Preliminary clinical trials, supported by solid basic research and strong preclinical evidence, promises a new era in the clinical management of these broad spectrum of malignant tumors. PMID- 22666002 TI - Submersible UV-Vis spectroscopy for quantifying streamwater organic carbon dynamics: implementation and challenges before and after forest harvest in a headwater stream. AB - Organic material, including total and dissolved organic carbon (DOC), is ubiquitous within aquatic ecosystems, playing a variety of important and diverse biogeochemical and ecological roles. Determining how land-use changes affect DOC concentrations and bioavailability within aquatic ecosystems is an important means of evaluating the effects on ecological productivity and biogeochemical cycling. This paper presents a methodology case study looking at the deployment of a submersible UV-Vis absorbance spectrophotometer (UV-Vis spectro::lyzer model, s::can, Vienna, Austria) to determine stream organic carbon dynamics within a headwater catchment located near Campbell River (British Columbia, Canada). Field-based absorbance measurements of DOC were made before and after forest harvest, highlighting the advantages of high temporal resolution compared to traditional grab sampling and laboratory measurements. Details of remote deployment are described. High-frequency DOC data is explored by resampling the 30 min time series with a range of resampling time intervals (from daily to weekly time steps). DOC export was calculated for three months from the post harvest data and resampled time series, showing that sampling frequency has a profound effect on total DOC export. DOC exports derived from weekly measurements were found to underestimate export by as much as 30% compared to DOC export calculated from high-frequency data. Additionally, the importance of the ability to remotely monitor the system through a recently deployed wireless connection is emphasized by examining causes of prior data losses, and how such losses may be prevented through the ability to react when environmental or power disturbances cause system interruption and data loss. PMID- 22666003 TI - A variant quorum sensing system in Aeromonas veronii MTCC 3249. AB - We have investigated the quorum sensing control in Aeromonas veronii MTCC 3249, originally isolated as A. culicicola from the midgut of Culex quinquefasciatus. Based on biosensor assays, the bacterium showed constant production of multiple acyl-homoserine lactones (AHLs) with increasing cell-density. The luxRI gene homologs, acuR (A. culicicola transcriptional Regulator) and acuI (A. culicicola autoInducer) were successfully amplified by inverse-PCR. Sequence analysis indicated acuRI were divergent from all known quorum sensing gene homologs in Aeromonas. Two localized regions in the C-terminal autoinducer binding domain of acuR showed indels suggesting variations in autoinducer specificity. Further, only a single copy of the quorum sensing genes was detected, suggesting a tight regulation of mechanisms under its control. Chromatography and further chemical analysis identified two AHLs in the culture supernatant: 6-carboxy-HHL (homoadipyl homoserine lactone), a novel AHL, and N-tetradecanoylhomoserine lactone. The existence of a potentially variant quorum sensing system might therefore, reflect in some way the ecological strategies adopted by this bacterium in the mosquito midgut. PMID- 22666004 TI - A neuro-inspired spike-based PID motor controller for multi-motor robots with low cost FPGAs. AB - In this paper we present a neuro-inspired spike-based close-loop controller written in VHDL and implemented for FPGAs. This controller has been focused on controlling a DC motor speed, but only using spikes for information representation, processing and DC motor driving. It could be applied to other motors with proper driver adaptation. This controller architecture represents one of the latest layers in a Spiking Neural Network (SNN), which implements a bridge between robotics actuators and spike-based processing layers and sensors. The presented control system fuses actuation and sensors information as spikes streams, processing these spikes in hard real-time, implementing a massively parallel information processing system, through specialized spike-based circuits. This spike-based close-loop controller has been implemented into an AER platform, designed in our labs, that allows direct control of DC motors: the AER-Robot. Experimental results evidence the viability of the implementation of spike-based controllers, and hardware synthesis denotes low hardware requirements that allow replicating this controller in a high number of parallel controllers working together to allow a real-time robot control. PMID- 22666005 TI - A fiber optic catalytic sensor for neutral atom measurements in oxygen plasma. AB - The presented sensor for neutral oxygen atom measurement in oxygen plasma is a catalytic probe which uses fiber optics and infrared detection system to measure the gray body radiation of the catalyst. The density of neutral atoms can be determined from the temperature curve of the probe, because the catalyst is heated predominantly by the dissipation of energy caused by the heterogeneous surface recombination of neutral atoms. The advantages of this sensor are that it is simple, reliable, easy to use, noninvasive, quantitative and can be used in plasma discharge regions. By using different catalyst materials the sensor can also be applied for detection of neutral atoms in other plasmas. Sensor design, operation, example measurements and new measurement procedure for systematic characterization are presented. PMID- 22666006 TI - Improvement of KinectTM sensor capabilities by fusion with laser sensing data using octree. AB - To enhance sensor capabilities, sensor data readings from different modalities must be fused. The main contribution of this paper is to present a sensor data fusion approach that can reduce Kinect(TM) sensor limitations. This approach involves combining laser with Kinect(TM) sensors. Sensor data is modelled in a 3D environment based on octrees using a probabilistic occupancy estimation. The Bayesian method, which takes into account the uncertainty inherent in the sensor measurements, is used to fuse the sensor information and update the 3D octree map. The sensor fusion yields a significant increase of the field of view of the Kinect(TM) sensor that can be used for robot tasks. PMID- 22666007 TI - Clinical application of surface plasmon resonance-based biosensors for fetal fibronectin detection. AB - Preterm birth is the leading cause of perinatal morbidity and mortality. Fetal fibronectin (fFN), a glycoprotein in the extracellular matrix of the amniotic membranes, is the most powerful biomarker for predicting the risk of preterm birth. Biosensors using the surface plasmon resonance (SPR) response are potentially useful in quantitatively measuring molecules. We established a standard calibration curve of SPR intensity against fFN concentration and used the SPR-based biosensor to detect fFN concentrations in the cervicovaginal secretions of pregnant women between 22 and 34 weeks of gestation. The calibration curve extends from 0.5 ng/mL to 100 ng/mL with an excellent correlation (R(2) = 0.985) based on standard fFN samples. A cutoff value of 50 ng/mL fFN concentration in commercial ELISA kits corresponds to a relative intensity of 17 arbitrary units (a.u.) in SPR. Thirty-two pregnant women were analyzed in our study. In 11 women, the SPR relative intensity was greater than or equal to 17 a.u., and in 21 women, the SPR relative intensity was less than 17 a.u. There were significant differences between the two groups in regular uterine contractions (p = 0.040), hospitalization for tocolysis (p = 0.049), and delivery weeks (p = 0.043). Our prospective study concluded that SPR-based biosensors can quantitatively measure fFN concentrations. These results reveal the potential utility of SPR-based biosensors in predicting the risk of preterm birth. PMID- 22666008 TI - Sensitivity enhancement of strain sensing utilizing a differential pair of fiber Bragg gratings. AB - In strain measurement applications, the matched fiber Bragg gratings (FBG) method is generally used to reduce temperature dependence effects. The FBG parameters have to be designed to meet the requirements by the particular application. The bandwidth and slope of the FBG has to be balanced well, according to the measurement range, accuracy and sensitivity. A sensitivity enhanced strain demodulation method without sacrificing the measurement range for FBG sensing systems is proposed and demonstrated utilizing a pair of reference FBGs. One of the reference FBGs and the sensing FBG have almost the same Bragg wavelength, while the other reference FBGs has a Bragg wavelength offset relative to the sensing FBG. Reflected optical signals from the sensing FBG pass through two reference FBGs, and subtract from each other after the detection. Doubled strain measurement sensitivity is obtained by static rail load experiments compared to the general matched grating approach, and further verified in dynamic load experiments. Experimental results indicate that such a method could be used for real-time rail strain monitoring applications. PMID- 22666009 TI - Monitoring and failure analysis of corroded bridge cables under fatigue loading using acoustic emission sensors. AB - Cables play an important role in cable-stayed systems, but are vulnerable to corrosion and fatigue damage. There is a dearth of studies on the fatigue damage evolution of corroded cable. In the present study, the acoustic emission (AE) technology is adopted to monitor the fatigue damage evolution process. First, the relationship between stress and strain is determined through a tensile test for corroded and non-corroded steel wires. Results show that the mechanical performance of corroded cables is changed considerably. The AE characteristic parameters for fatigue damage are then established. AE energy cumulative parameters can accurately describe the fatigue damage evolution of corroded cables. The failure modes in each phase as well as the type of acoustic emission source are determined based on the results of scanning electron microscopy. The waveform characteristics, damage types, and frequency distribution of the corroded cable at different damage phases are collected. Finally, the number of broken wires and breakage time of the cables are determined according to the variation in the margin index. PMID- 22666010 TI - Dithiooxamide modified glassy carbon electrode for the studies of non-aqueous media: electrochemical behaviors of quercetin on the electrode surface. AB - Electrochemical oxidation of quercetin, as an important biological molecule, has been studied in non-aqueous media using cyclic voltammetry, electrochemical impedance spectroscopy and scanning electron microscopy. To investigate the electrochemical properties of quercetin, an important flavonoid derivative, on a different surface, a new glassy carbon electrode has been developed using dithiooxamide as modifier in non-aqueous media. The surface modification of glassy carbon electrode has been performed within the 0.0 mV and +800 mV potential range with 20 cycles using 1 mM dithioxamide solution in acetonitrile. However, the modification of quercetin to both bare glassy carbon and dithiooxamide modified glassy carbon electrode surface was carried out in a wide +300 mV and +2,800 mV potential range with 10 cycles. Following the modification process, cyclic voltammetry has been used for the surface characterization in aqueous and non-aqueous media whereas electrochemical impedance spectroscopy has been used in aqueous media. Scanning electron microscopy has also been used to support the surface analysis. The obtained data from the characterization and modification studies of dithioxamide modified and quercetin grafted glassy carbon electrode showed that the developed electrode can be used for the quantitative determination of quercetin and antioxidant capacity determination as a chemical sensor electrode. PMID- 22666011 TI - Optical fiber networks for remote fiber optic sensors. AB - This paper presents an overview of optical fiber sensor networks for remote sensing. Firstly, the state of the art of remote fiber sensor systems has been considered. We have summarized the great evolution of these systems in recent years; this progress confirms that fiber-optic remote sensing is a promising technology with a wide field of practical applications. Afterwards, the most representative remote fiber-optic sensor systems are briefly explained, discussing their schemes, challenges, pros and cons. Finally, a synopsis of the main factors to take into consideration in the design of a remote sensor system is gathered. PMID- 22666012 TI - A CMOS-compatible poly-Si nanowire device with hybrid sensor/memory characteristics for System-on-Chip applications. AB - This paper reports a versatile nano-sensor technology using "top-down" poly silicon nanowire field-effect transistors (FETs) in the conventional Complementary Metal-Oxide Semiconductor (CMOS)-compatible semiconductor process. The nanowire manufacturing technique reduced nanowire width scaling to 50 nm without use of extra lithography equipment, and exhibited superior device uniformity. These n type polysilicon nanowire FETs have positive pH sensitivity (100 mV/pH) and sensitive deoxyribonucleic acid (DNA) detection ability (100 pM) at normal system operation voltages. Specially designed oxide-nitride-oxide buried oxide nanowire realizes an electrically V(th)-adjustable sensor to compensate device variation. These nanowire FETs also enable non-volatile memory application for a large and steady V(th) adjustment window (>2 V Programming/Erasing window). The CMOS-compatible manufacturing technique of polysilicon nanowire FETs offers a possible solution for commercial System-on Chip biosensor application, which enables portable physiology monitoring and in situ recording. PMID- 22666014 TI - An environmental monitoring system for managing spatiotemporal sensor data over sensor networks. AB - In a wireless sensor network, sensors collect data about natural phenomena and transmit them to a server in real-time. Many studies have been conducted focusing on the processing of continuous queries in an approximate form. However, this approach is difficult to apply to environmental applications which require the correct data to be stored. In this paper, we propose a weather monitoring system for handling and storing the sensor data stream in real-time in order to support continuous spatial and/or temporal queries. In our system, we exploit two time based insertion methods to store the sensor data stream and reduce the number of managed tuples, without losing any of the raw data which are useful for queries, by using the sensors' temporal attributes. In addition, we offer a method for reducing the cost of the join operations used in processing spatiotemporal queries by filtering out a list of irrelevant sensors from query range before making a join operation. In the results of the performance evaluation, the number of tuples obtained from the data stream is reduced by about 30% in comparison to a naive approach, thereby decreasing the query execution time. PMID- 22666015 TI - Inhibition of quorum sensing-controlled virulence factor production in Pseudomonas aeruginosa PAO1 by Ayurveda spice clove (Syzygium aromaticum) bud extract. AB - Quorum sensing controls the virulence determinants in most proteobacteria. In this work, the hexane, chloroform and methanol extracts of an Ayurveda spice, namely clove (Syzygium aromaticum), shown anti-quorum sensing activity. Hexane and methanol extracts of clove inhibited the response of C. violaceum CV026 to exogenously supplied N-hexanoylhomoserine lactone, in turn preventing violacein production. Chloroform and methanol extracts of clove significantly reduced bioluminescence production by E. coli [pSB1075] grown in the presence of N-(3 oxododecanoyl)-L-homoserine lactone. We demonstrated that clove extract inhibited quorum sensing-regulated phenotypes in Pseudomonas aeruginosa PA01, including expression of lecA::lux (by hexane extract), swarming (maximum inhibition by methanol extract), pyocyanin (maximum inhibition by hexane extract). This study shows that the presence of natural compounds that exhibit anti-quorum sensing activity in the clove extracts may be useful as the lead of anti-infective drugs. PMID- 22666016 TI - Sensor and sensorless fault tolerant control for induction motors using a wavelet index. AB - Fault Tolerant Control (FTC) systems are crucial in industry to ensure safe and reliable operation, especially of motor drives. This paper proposes the use of multiple controllers for a FTC system of an induction motor drive, selected based on a switching mechanism. The system switches between sensor vector control, sensorless vector control, closed-loop voltage by frequency (V/f) control and open loop V/f control. Vector control offers high performance, while V/f is a simple, low cost strategy with high speed and satisfactory performance. The faults dealt with are speed sensor failures, stator winding open circuits, shorts and minimum voltage faults. In the event of compound faults, a protection unit halts motor operation. The faults are detected using a wavelet index. For the sensorless vector control, a novel Boosted Model Reference Adaptive System (BMRAS) to estimate the motor speed is presented, which reduces tuning time. Both simulation results and experimental results with an induction motor drive show the scheme to be a fast and effective one for fault detection, while the control methods transition smoothly and ensure the effectiveness of the FTC system. The system is also shown to be flexible, reverting rapidly back to the dominant controller if the motor returns to a healthy state. PMID- 22666017 TI - A novel integrated multifunction micro-sensor for three-dimensional micro-force measurements. AB - An integrated multifunction micro-sensor for three-dimensional micro-force precision measurement under different pressure and temperature conditions is introduced in this paper. The integrated sensor consists of three kinds of sensors: a three-dimensional micro-force sensor, an absolute pressure sensor and a temperature sensor. The integrated multifunction micro-sensor is fabricated on silicon wafers by micromachining technology. Different doping doses of boron ion, placement and structure of resistors are tested for the force sensor, pressure sensor and temperature sensor to minimize the cross interference and optimize the properties. A glass optical fiber, with a ladder structure and sharp tip etched by buffer oxide etch solution, is glued on the micro-force sensor chip as the tactile probe. Experimental results show that the minimum force that can be detected by the force sensor is 300 nN; the lateral sensitivity of the force sensor is 0.4582 mV/MUN; the probe length is linearly proportional to sensitivity of the micro-force sensor in lateral; the sensitivity of the pressure sensor is 0.11 mv/KPa; the sensitivity of the temperature sensor is 5.836 * 10(-3) KOmega/ degrees C. Thus it is a cost-effective method to fabricate integrated multifunction micro-sensors with different measurement ranges that could be used in many fields. PMID- 22666019 TI - Equations for solar tracking. AB - Direct sunlight absorption by trace gases can be used to quantify them and investigate atmospheric chemistry. In such experiments, the main optical apparatus is often a grating or a Fourier transform spectrometer. A solar tracker based on motorized rotating mirrors is commonly used to direct the light along the spectrometer axis, correcting for the apparent rotation of the Sun. Calculating the Sun azimuth and altitude for a given time and location can be achieved with high accuracy but different sources of angular offsets appear in practice when positioning the mirrors. A feedback on the motors, using a light position sensor close to the spectrometer, is almost always needed. This paper aims to gather the main geometrical formulas necessary for the use of a widely used kind of solar tracker, based on two 45 degrees mirrors in altazimuthal set up with a light sensor on the spectrometer, and to illustrate them with a tracker developed by our group for atmospheric research. PMID- 22666018 TI - Quorum quenching Bacillus sonorensis isolated from soya sauce fermentation brine. AB - An N-acylhomoserine lactone (AHL)-degrading bacterial strain, L62, was isolated from a sample of fermentation brine of Chinese soya sauce by using rich medium agar supplemented with soya sauce (10% v/v). L62, a rod-shaped Gram positive bacterium with amylolytic activity, was phylogentically related to Bacillus sonorensis by 16S ribosomal DNA and rpoB sequence analyses. B. sonorensis L62 efficiently degraded N-3-oxohexanoyl homoserine lactone and N-octanoylhomoserine lactone. However, the aiiA homologue, encoding an autoinducer inactivation enzyme catalyzing the degradation of AHLs, was not detected in L62, suggesting the presence of a different AHL-degrading gene in L62. To the best of our knowledge, this is the first report of AHL-degrading B. sonorensis from soya sauce liquid state fermentation. PMID- 22666020 TI - Fast direct injection mass-spectrometric characterization of stimuli for insect electrophysiology by proton transfer reaction-time of flight mass-spectrometry (PTR-ToF-MS). AB - Electrophysiological techniques are used in insect neuroscience to measure the response of olfactory neurons to volatile odour stimuli. Widely used systems to deliver an olfactory stimulus to a test insect include airstream guided flow through glass cartridges loaded with a given volatile compound on a sorbent support. Precise measurement of the quantity of compound reaching the sensory organ of the test organism is an urgent task in insect electrophysiology. In this study we evaluated the performances of the recent realised proton transfer reaction-time of flight mass-spectrometry (PTR-ToF-MS) as a fast and selective gas sensor. In particular, we characterised the gas emission from cartridges loaded with a set of volatile compounds belonging to different chemical classes and commonly used in electrophysiological experiments. PTR-ToF-MS allowed a fast monitoring of all investigated compounds with sufficient sensitivity and time resolution. The detection and the quantification of air contaminants and solvent or synthetic standards impurities allowed a precise quantification of the stimulus exiting the cartridge. The outcome of this study was twofold: on one hand we showed that PTR-ToF-MS allows monitoring fast processes with high sensitivity by real time detection of a broad number of compounds; on the other hand we provided a tool to solve an important issue in insect electrophysiology. PMID- 22666021 TI - Effect of functional group and carbon chain length on the odor detection threshold of aliphatic compounds. AB - Odor detection thresholds (ODTs) are used for assessing outdoor and indoor air quality. They are obtained experimentally by olfactometry and psychophysical methods, and large compilations are available in the literature. A non-linear regression equation was fitted to describe the ODT variability of 114 aliphatic compounds based on the alkyl chain length for different homologous series (carboxylic acids, aldehydes, 2-ketones, esters, 1-alcohols, amines, thiols, thioethers and hydrocarbons). The resulting equation reveals an effect of the functional group, molecular size and also an interaction between both factors. Although the mechanistic interpretation of results is uncertain, the relatively high goodness-of-fit (R(2) = 0.90) suggests that ODT values of aliphatic compounds can be predicted rather accurately, which is not the case for rigid molecules. This equation may serve as a basis for the development of more complex ODT models taking into account diverse structural features of odorants. The variability of power-law exponents was also investigated for the homologous series. PMID- 22666022 TI - Acoustic transmitters for underwater neutrino telescopes. AB - In this paper acoustic transmitters that were developed for use in underwater neutrino telescopes are presented. Firstly, an acoustic transceiver has been developed as part of the acoustic positioning system of neutrino telescopes. These infrastructures are not completely rigid and require a positioning system in order to monitor the position of the optical sensors which move due to sea currents. To guarantee a reliable and versatile system, the transceiver has the requirements of reduced cost, low power consumption, high pressure withstanding (up to 500 bars), high intensity for emission, low intrinsic noise, arbitrary signals for emission and the capacity of acquiring and processing received signals. Secondly, a compact acoustic transmitter array has been developed for the calibration of acoustic neutrino detection systems. The array is able to mimic the signature of ultra-high-energy neutrino interaction in emission directivity and signal shape. The technique of parametric acoustic sources has been used to achieve the proposed aim. The developed compact array has practical features such as easy manageability and operation. The prototype designs and the results of different tests are described. The techniques applied for these two acoustic systems are so powerful and versatile that may be of interest in other marine applications using acoustic transmitters. PMID- 22666023 TI - Differential binary encoding method for calibrating image sensors based on IOFBs. AB - Image transmission using incoherent optical fiber bundles (IOFBs) requires prior calibration to obtain the spatial in-out fiber correspondence necessary to reconstruct the image captured by the pseudo-sensor. This information is recorded in a Look-Up Table called the Reconstruction Table (RT), used later for reordering the fiber positions and reconstructing the original image. This paper presents a very fast method based on image-scanning using spaces encoded by a weighted binary code to obtain the in-out correspondence. The results demonstrate that this technique yields a remarkable reduction in processing time and the image reconstruction quality is very good compared to previous techniques based on spot or line scanning, for example. PMID- 22666024 TI - Spatial heterogeneity of autoinducer regulation systems. AB - Autoinducer signals enable coordinated behaviour of bacterial populations, a phenomenon originally described as quorum sensing. Autoinducer systems are often controlled by environmental substances as nutrients or secondary metabolites (signals) from neighbouring organisms. In cell aggregates and biofilms gradients of signals and environmental substances emerge. Mathematical modelling is used to analyse the functioning of the system. We find that the autoinducer regulation network generates spatially heterogeneous behaviour, up to a kind of multicellularity-like division of work, especially under nutrient-controlled conditions. A hybrid push/pull concept is proposed to explain the ecological function. The analysis allows to explain hitherto seemingly contradicting experimental findings. PMID- 22666025 TI - A high sensitivity three-dimensional-shape sensing patch prepared by lithography and inkjet printing. AB - A process combining conventional photolithography and a novel inkjet printing method for the manufacture of high sensitivity three-dimensional-shape (3DS) sensing patches was proposed and demonstrated. The supporting curvature ranges from 1.41 to 6.24 * 10(-2) mm(-1) and the sensing patch has a thickness of less than 130 MUm and 20 * 20 mm(2) dimensions. A complete finite element method (FEM) model with simulation results was calculated and performed based on the buckling of columns and the deflection equation. The results show high compatibility of the drop-on-demand (DOD) inkjet printing with photolithography and the interferometer design also supports bi-directional detection of deformation. The 3DS sensing patch can be operated remotely without any power consumption. It provides a novel and alternative option compared with other optical curvature sensors. PMID- 22666026 TI - Measurements and modelling of base station power consumption under real traffic loads. AB - Base stations represent the main contributor to the energy consumption of a mobile cellular network. Since traffic load in mobile networks significantly varies during a working or weekend day, it is important to quantify the influence of these variations on the base station power consumption. Therefore, this paper investigates changes in the instantaneous power consumption of GSM (Global System for Mobile Communications) and UMTS (Universal Mobile Telecommunications System) base stations according to their respective traffic load. The real data in terms of the power consumption and traffic load have been obtained from continuous measurements performed on a fully operated base station site. Measurements show the existence of a direct relationship between base station traffic load and power consumption. According to this relationship, we develop a linear power consumption model for base stations of both technologies. This paper also gives an overview of the most important concepts which are being proposed to make cellular networks more energy-efficient. PMID- 22666027 TI - Reducing false negative reads in RFID data streams using an adaptive sliding window approach. AB - Unreliability of the data streams generated by RFID readers is among the primary factors which limit the widespread adoption of the RFID technology. RFID data cleaning is, therefore, an essential task in the RFID middleware systems in order to reduce reading errors, and to allow these data streams to be used to make a correct interpretation and analysis of the physical world they are representing. In this paper we propose an adaptive sliding-window based approach called WSTD which is capable of efficiently coping with both environmental variation and tag dynamics. Our experimental results demonstrate the efficacy of the proposed approach. PMID- 22666028 TI - A real-time measurement system for long-life flood monitoring and warning applications. AB - A flood warning system incorporates telemetered rainfall and flow/water level data measured at various locations in the catchment area. Real-time accurate data collection is required for this use, and sensor networks improve the system capabilities. However, existing sensor nodes struggle to satisfy the hydrological requirements in terms of autonomy, sensor hardware compatibility, reliability and long-range communication. We describe the design and development of a real-time measurement system for flood monitoring, and its deployment in a flash-flood prone 650 km(2) semiarid watershed in Southern Spain. A developed low-power and long-range communication device, so-called DatalogV1, provides automatic data gathering and reliable transmission. DatalogV1 incorporates self-monitoring for adapting measurement schedules for consumption management and to capture events of interest. Two tests are used to assess the success of the development. The results show an autonomous and robust monitoring system for long-term collection of water level data in many sparse locations during flood events. PMID- 22666029 TI - Underwater wireless sensor communications in the 2.4 GHz ISM frequency band. AB - One of the main problems in underwater communications is the low data rate available due to the use of low frequencies. Moreover, there are many problems inherent to the medium such as reflections, refraction, energy dispersion, etc., that greatly degrade communication between devices. In some cases, wireless sensors must be placed quite close to each other in order to take more accurate measurements from the water while having high communication bandwidth. In these cases, while most researchers focus their efforts on increasing the data rate for low frequencies, we propose the use of the 2.4 GHz ISM frequency band in these special cases. In this paper, we show our wireless sensor node deployment and its performance obtained from a real scenario and measures taken for different frequencies, modulations and data transfer rates. The performed tests show the maximum distance between sensors, the number of lost packets and the average round trip time. Based on our measurements, we provide some experimental models of underwater communication in fresh water using EM waves in the 2.4 GHz ISM frequency band. Finally, we compare our communication system proposal with the existing systems. Although our proposal provides short communication distances, it provides high data transfer rates. It can be used for precision monitoring in applications such as contaminated ecosystems or for device communicate at high depth. PMID- 22666030 TI - Parametric study of the reflective periodic grating for in-plane displacement measurement using optical fibers. AB - This paper presents a technique for a simple sensing principle that can be used for the measurement of displacement. The proposed sensor head is composed of a reflective grating panel and an optical fiber as a transceiver. The simplified layout contributes to resolving the issues of space restraints during installation and complex cabling problems in transmission fiber optic sensors. In order to verify the effectiveness of the proposed technique, it is important to obtain the sinusoidal signal reflected from the grating for reasonable phase tracking. In the numerical analysis, a real wave based optical beam model is proposed for the extraction of predicted signal according to the grating width and ratio of reflection bar width to spacing. The grating pattern design to obtain a sine wave reflected sensor signal was determined within an R-square value of 0.98 after sine curve fitting analysis. Consequently, the proposed sensor principle achieved the in-plane displacement measurement with a maximum accuracy error of 5.34 MUm. PMID- 22666031 TI - Application of optical biosensors in small-molecule screening activities. AB - The last two decades have seen remarkable progress and improvements in optical biosensor systems such that those are currently seen as an important and value adding component of modern drug screening activities. In particular the introduction of microplate-based biosensor systems holds the promise to match the required throughput without compromising on data quality thus representing a sought-after complement to traditional fluidic systems. This article aims to highlight the application of the two most prominent optical biosensor technologies, namely surface plasmon resonance (SPR) and optical waveguide grating (OWG), in small-molecule screening and will present, review and discuss the advantages and disadvantages of different assay formats on these platforms. A particular focus will be on the specific advantages of the inhibition in solution assay (ISA) format in contrast to traditional direct binding assays (DBA). Furthermore we will discuss different application areas for both fluidic as well as plate-based biosensor systems by considering the individual strength of the platforms. PMID- 22666032 TI - Integrating iris and signature traits for personal authentication using user specific weighting. AB - Biometric systems based on uni-modal traits are characterized by noisy sensor data, restricted degrees of freedom, non-universality and are susceptible to spoof attacks. Multi-modal biometric systems seek to alleviate some of these drawbacks by providing multiple evidences of the same identity. In this paper, a user-score-based weighting technique for integrating the iris and signature traits is presented. This user-specific weighting technique has proved to be an efficient and effective fusion scheme which increases the authentication accuracy rate of multi-modal biometric systems. The weights are used to indicate the importance of matching scores output by each biometrics trait. The experimental results show that our biometric system based on the integration of iris and signature traits achieve a false rejection rate (FRR) of 0.08% and a false acceptance rate (FAR) of 0.01%. PMID- 22666034 TI - A reverse localization scheme for underwater acoustic sensor networks. AB - Underwater Wireless Sensor Networks (UWSNs) provide new opportunities to observe and predict the behavior of aquatic environments. In some applications like target tracking or disaster prevention, sensed data is meaningless without location information. In this paper, we propose a novel 3D centralized, localization scheme for mobile underwater wireless sensor network, named Reverse Localization Scheme or RLS in short. RLS is an event-driven localization method triggered by detector sensors for launching localization process. RLS is suitable for surveillance applications that require very fast reactions to events and could report the location of the occurrence. In this method, mobile sensor nodes report the event toward the surface anchors as soon as they detect it. They do not require waiting to receive location information from anchors. Simulation results confirm that the proposed scheme improves the energy efficiency and reduces significantly localization response time with a proper level of accuracy in terms of mobility model of water currents. Major contributions of this method lie on reducing the numbers of message exchange for localization, saving the energy and decreasing the average localization response time. PMID- 22666033 TI - Silencing quorum sensing through extracts of Melicope lunu-ankenda. AB - Quorum sensing regulates bacterial virulence determinants, therefore making it an interesting target to attenuate pathogens. In this work, we screened edible, endemic plants in Malaysia for anti-quorum sensing properties. Extracts from Melicope lunu-ankenda (Gaertn.) T. G. Hartley, a Malay garden salad, inhibited response of Chromobacterium violaceum CV026 to N-hexanoylhomoserine lactone, thus interfering with violacein production; reduced bioluminescence expression of E. coli [pSB401], disrupted pyocyanin synthesis, swarming motility and expression of lecA::lux of Pseudomonas aeruginosa PAO1. Although the chemical nature of the anti-QS compounds from M. lunu-ankenda is currently unknown, this study proves that endemic Malaysian plants could serve as leads in the search for anti-quorum sensing compounds. PMID- 22666035 TI - Adaptive redundant lifting wavelet transform based on fitting for fault feature extraction of roller bearings. AB - A least square method based on data fitting is proposed to construct a new lifting wavelet, together with the nonlinear idea and redundant algorithm, the adaptive redundant lifting transform based on fitting is firstly stated in this paper. By variable combination selections of basis function, sample number and dimension of basis function, a total of nine wavelets with different characteristics are constructed, which are respectively adopted to perform redundant lifting wavelet transforms on low-frequency approximate signals at each layer. Then the normalized l(P) norms of the new node-signal obtained through decomposition are calculated to adaptively determine the optimal wavelet for the decomposed approximate signal. Next, the original signal is taken for subsection power spectrum analysis to choose the node-signal for single branch reconstruction and demodulation. Experiment signals and engineering signals are respectively used to verify the above method and the results show that bearing faults can be diagnosed more effectively by the method presented here than by both spectrum analysis and demodulation analysis. Meanwhile, compared with the symmetrical wavelets constructed with Lagrange interpolation algorithm, the asymmetrical wavelets constructed based on data fitting are more suitable in feature extraction of fault signal of roller bearings. PMID- 22666036 TI - Optical triangulation-based microtopographic inspection of surfaces. AB - The non-invasive inspection of surfaces is a major issue in a wide variety of industries and research laboratories. The vast and increasing range of surface types, tolerance requirements and measurement constraints demanded during the last decades represents a major research effort in the development of new methods, systems and metrological strategies. The discreet dimensional evaluation the rugometric characterization and the profilometric inspection seem to be insufficient in many instances. The full microtopographic inspection has became a common requirement. Among the different systems developed, optical methods have the most important role and among those triangulation-based ones have gained a major status thanks to their flexibility, reliability and robustness. In this communication we will provide a brief historical review on the development of optical triangulation application to the dimensional inspection of objects and surfaces and on the work done at the Microtopography Laboratory of the Physics Department of the University of Minho, Portugal, in the development of methods and systems of optical triangulation-based microtopographic inspection of surfaces. PMID- 22666038 TI - A vision based top-view transformation model for a vehicle parking assistant. AB - This paper proposes the Top-View Transformation Model for image coordinate transformation, which involves transforming a perspective projection image into its corresponding bird's eye vision. A fitting parameters searching algorithm estimates the parameters that are used to transform the coordinates from the source image. Using this approach, it is not necessary to provide any interior and exterior orientation parameters of the camera. The designed car parking assistant system can be installed at the rear end of the car, providing the driver with a clearer image of the area behind the car. The processing time can be reduced by storing and using the transformation matrix estimated from the first image frame for a sequence of video images. The transformation matrix can be stored as the Matrix Mapping Table, and loaded into the embedded platform to perform the transformation. Experimental results show that the proposed approaches can provide a clearer and more accurate bird's eye view to the vehicle driver. PMID- 22666037 TI - 2:1 multiplexing function in a simple molecular system. AB - 1-[(Anthracen-9-yl)methylene] thiosemicarbazide shows weak fluorescence due to a photo-induced electron transfer (PET) process from the thiosemicarbazide moiety to the excited anthracene. The anthracene emission can be recovered via protonation of the amine as the protonated aminomethylene as an electron withdrawing group that suppresses the PET process. Similarly, chelation between the ligand and the metal ions can also suppress the PET process and results in a fluorescence enhancement (CHEF). When solvents are introduced as the third control, a molecular 2:1 multiplexer is constructed to report selectively the inputs. Therefore, a molecular 2:1 multiplexer is realized in a simple molecular system. PMID- 22666039 TI - Gamma irradiation of magnetoresistive sensors for planetary exploration. AB - A limited number of Anisotropic Magnetoresistive (AMR) commercial-off-the-shelf (COTS) magnetic sensors of the HMC series by Honeywell, with and without integrated front-end electronics, were irradiated with gamma rays up to a total irradiation dose of 200 krad (Si), following the ESCC Basic Specification No. 22900. Due to the magnetic cleanliness required for these tests a special set-up was designed and successfully employed. Several parameters of the sensors were monitored during testing and the results are reported in this paper. The authors conclude that AMR sensors without front-end electronics seem to be robust against radiation doses of up to 200 krad (Si) with a dose rate of 5 krad (Si)/hour and up to a resolution of tens of nT, but sensors with an integrated front-end seem to be more vulnerable to radiation. PMID- 22666040 TI - An advanced compiler designed for a VLIW DSP for sensors-based systems. AB - The VLIW architecture can be exploited to greatly enhance instruction level parallelism, thus it can provide computation power and energy efficiency advantages, which satisfies the requirements of future sensor-based systems. However, as VLIW codes are mainly compiled statically, the performance of a VLIW processor is dominated by the behavior of its compiler. In this paper, we present an advanced compiler designed for a VLIW DSP named Magnolia, which will be used in sensor-based systems. This compiler is based on the Open64 compiler. We have implemented several advanced optimization techniques in the compiler, and fulfilled the O3 level optimization. Benchmarks from the DSPstone test suite are used to verify the compiler. Results show that the code generated by our compiler can make the performance of Magnolia match that of the current state-of-the-art DSP processors. PMID- 22666041 TI - Pressure and temperature spin crossover sensors with optical detection. AB - Iron(II) spin crossover molecular materials are made of coordination centres switchable between two states by temperature, pressure or a visible light irradiation. The relevant macroscopic parameter which monitors the magnetic state of a given solid is the high-spin (HS) fraction denoted n(HS), i.e., the relative population of HS molecules. Each spin crossover material is distinguished by a transition temperature T(1/2) where 50% of active molecules have switched to the low-spin (LS) state. In strongly interacting systems, the thermal spin switching occurs abruptly at T(1/2). Applying pressure induces a shift from HS to LS states, which is the direct consequence of the lower volume for the LS molecule. Each material has thus a well defined pressure value P(1/2). In both cases the spin state change is easily detectable by optical means thanks to a thermo/piezochromic effect that is often encountered in these materials. In this contribution, we discuss potential use of spin crossover molecular materials as temperature and pressure sensors with optical detection. The ones presenting smooth transitions behaviour, which have not been seriously considered for any application, are spotlighted as potential sensors which should stimulate a large interest on this well investigated class of materials. PMID- 22666042 TI - Evaluation of commercial probes for on-line electrical conductivity measurements during goat gland milking process. AB - The measurement of the milk electrical conductivity (EC) during mechanical milking has been widely studied for mastitis detection on cows because its improving of welfare and animal health, although research about small ruminants is scarce. The aim of this study was to evaluate the performance of three commercial conductimeters to be used during mechanical milking of small ruminant halves, especially Murciano-Granadina goats. The objective of this research was to integrate the probes on the milking unit and to check the suitability of the probe selected. The results presented in this research have guided authors to discard the commercial probes and to establish the requirements of a new probe design that is briefly outlined in the conclusions of this contribution. PMID- 22666043 TI - An instrument for in situ measuring the volume scattering function of water: design, calibration and primary experiments. AB - The optical volume scattering function (VSF) of seawater is a fundamental property used in the calculation of radiative transfer for applications in the study of the upper-ocean heat balance, the photosynthetic productivity of the ocean, and the chemical transformation of photoreactive compounds. A new instrument to simultaneously measure the VSF in seven directions between 20 degrees to 160 degrees , the attenuation coefficient, and the depth of water is presented. The instrument is self-contained and can be automatically controlled by the depth under water. The self-contained data can be easily downloaded by an ultra-short-wave communication system. A calibration test was performed in the laboratory based on precise estimation of the scattering volume and optical radiometric calibration of the detectors. The measurement error of the VSF measurement instrument has been estimated in the laboratory based on the Mie theory, and the average error is less than 12%. The instrument was used to measure and analyze the variation characteristics of the VSF with angle, depth and water quality in Daya Bay for the first time. From these in situ data, we have found that the phase functions proposed by Fournier-Forand, measured by Petzold in San Diego Harbor and Sokolov in Black Sea do not fit with our measurements in Daya. These discrepancies could manly due to high proportion of suspended calcium carbonate mineral-like particles with high refractive index in Daya Bay. PMID- 22666044 TI - The application of LiDAR to assessment of rooftop solar photovoltaic deployment potential in a municipal district unit. AB - A methodology is provided for the application of Light Detection and Ranging (LiDAR) to automated solar photovoltaic (PV) deployment analysis on the regional scale. Challenges in urban information extraction and management for solar PV deployment assessment are determined and quantitative solutions are offered. This paper provides the following contributions: (i) a methodology that is consistent with recommendations from existing literature advocating the integration of cross disciplinary competences in remote sensing (RS), GIS, computer vision and urban environmental studies; (ii) a robust methodology that can work with low resolution, incomprehensive data and reconstruct vegetation and building separately, but concurrently; (iii) recommendations for future generation of software. A case study is presented as an example of the methodology. Experience from the case study such as the trade-off between time consumption and data quality are discussed to highlight a need for connectivity between demographic information, electrical engineering schemes and GIS and a typical factor of solar useful roofs extracted per method. Finally, conclusions are developed to provide a final methodology to extract the most useful information from the lowest resolution and least comprehensive data to provide solar electric assessments over large areas, which can be adapted anywhere in the world. PMID- 22666045 TI - A network coding based routing protocol for underwater sensor networks. AB - Due to the particularities of the underwater environment, some negative factors will seriously interfere with data transmission rates, reliability of data communication, communication range, and network throughput and energy consumption of underwater sensor networks (UWSNs). Thus, full consideration of node energy savings, while maintaining a quick, correct and effective data transmission, extending the network life cycle are essential when routing protocols for underwater sensor networks are studied. In this paper, we have proposed a novel routing algorithm for UWSNs. To increase energy consumption efficiency and extend network lifetime, we propose a time-slot based routing algorithm (TSR).We designed a probability balanced mechanism and applied it to TSR. The theory of network coding is introduced to TSBR to meet the requirement of further reducing node energy consumption and extending network lifetime. Hence, time-slot based balanced network coding (TSBNC) comes into being. We evaluated the proposed time slot based balancing routing algorithm and compared it with other classical underwater routing protocols. The simulation results show that the proposed protocol can reduce the probability of node conflicts, shorten the process of routing construction, balance energy consumption of each node and effectively prolong the network lifetime. PMID- 22666046 TI - Long-period fiber grating sensors for the measurement of liquid level and fluid flow velocity. AB - This paper presents the development and assessment of two types of Long Period Fiber Grating (LPFG)-based sensors including a mobile liquid level sensor and a reflective sensor for the measurement of liquid level and fluid-flow velocity. Shewhart control charts were used to assess the liquid level sensing capacity and reliability of the mobile CO(2)-laser engraved LPFG sensor. There were ten groups of different liquid level experiment and each group underwent ten repeated wavelength shift measurements. The results showed that all measurands were within the control limits; thus, this mobile sensor was reliable and exhibited at least 100-cm liquid level measurement capacity. In addition, a reflective sensor consisting of five LPFGs in series with a reflective end has been developed to evaluate the liquid level and fluid-flow velocity. These five LPFGs were fabricated by the electrical arc discharge method and the reflective end was coated with silver by Tollen's test. After each liquid level experiment was performed five times, the average values of the resonance wavelength shifts for LPFG Nos. 1-5 were in the range of 1.35-9.14 nm. The experimental findings showed that the reflective sensor could be used to automatically monitor five fixed liquid levels. This reflective sensor also exhibited at least 100-cm liquid level measurement capacity. The mechanism of the fluid-flow velocity sensor was based on analyzing the relationship among the optical power, time, and the LPFG's length. There were two types of fluid-flow velocity measurements: inflow and drainage processes. The differences between the LPFG-based fluid-flow velocities and the measured average fluid-flow velocities were found in the range of 8.7 12.6%. For the first time to our knowledge, we have demonstrated the feasibility of liquid level and fluid-flow velocity sensing with a reflective LPFG-based sensor without modifying LPFGs or coating chemical compounds. PMID- 22666047 TI - Template free synthesis of hollow ball-like nano-Fe2O3 and its application to the detection of dimethyl methylphosphonate at room temperature. AB - This paper is focused on the template-free synthesis of nanosized ferric oxide (nano-Fe(2)O(3)) and its application in quartz crystal microbalance (QCM) resonators to detect dimethyl methylphosphonate (DMMP), a simulant of Sarin. The X-ray diffraction (XRD) patterns confirm that the synthesized samples are made of Fe(2)O(3) and the scanning electron microscopy (SEM) pictures show that the samples have ball-like shapes. The DMMP sensors with a sensing film of hollow ball-like and solid ball-like Fe(2)O(3) are fabricated and their sensing characteristics are compared. The sensitivity of the hollow ball-like Fe(2)O(3) sensor is more than 500% higher than the one of the solid ball-like Fe(2)O(3) sensor. The hollow ball-like nano-Fe(2)O(3) can be synthesized by a novel low temperature hydrothermal method. The sensors with the hollow ball-like Fe(2)O(3) film perform well in a range of 1 to 6 ppm, with a sensitivity of 29 Hz/ppm at room temperature, while the appropriate recoverability and selectivity are maintained. In addition, the performance of different thicknesses of the sensing film of the hollow ball-like nano-Fe(2)O(3) is investigated and the optimized relative film thickness of the hollow ball-like nano-Fe(2)O(3) is found to be 20 MUg/mm(2). PMID- 22666048 TI - A neural network approach to smarter sensor networks for water quality monitoring. AB - Environmental monitoring is evolving towards large-scale and low-cost sensor networks operating reliability and autonomously over extended periods of time. Sophisticated analytical instrumentation such as chemo-bio sensors present inherent limitations because of the number of samples that they can take. In order to maximize their deployment lifetime, we propose the coordination of multiple heterogeneous information sources. We use rainfall radar images and information from a water depth sensor as input to a neural network (NN) to dictate the sampling frequency of a phosphate analyzer at the River Lee in Cork, Ireland. This approach shows varied performance for different times of the year but overall produces output that is very satisfactory for the application context in question. Our study demonstrates that even with limited training data, a system for controlling the sampling rate of the nutrient sensor can be set up and can improve the efficiency of the more sophisticated nodes of the sensor network. PMID- 22666049 TI - Multispectral palmprint recognition using a quaternion matrix. AB - Palmprints have been widely studied for biometric recognition for many years. Traditionally, a white light source is used for illumination. Recently, multispectral imaging has drawn attention because of its high recognition accuracy. Multispectral palmprint systems can provide more discriminant information under different illuminations in a short time, thus they can achieve better recognition accuracy. Previously, multispectral palmprint images were taken as a kind of multi-modal biometrics, and the fusion scheme on the image level or matching score level was used. However, some spectral information will be lost during image level or matching score level fusion. In this study, we propose a new method for multispectral images based on a quaternion model which could fully utilize the multispectral information. Firstly, multispectral palmprint images captured under red, green, blue and near-infrared (NIR) illuminations were represented by a quaternion matrix, then principal component analysis (PCA) and discrete wavelet transform (DWT) were applied respectively on the matrix to extract palmprint features. After that, Euclidean distance was used to measure the dissimilarity between different features. Finally, the sum of two distances and the nearest neighborhood classifier were employed for recognition decision. Experimental results showed that using the quaternion matrix can achieve a higher recognition rate. Given 3000 test samples from 500 palms, the recognition rate can be as high as 98.83%. PMID- 22666050 TI - Precise temperature mapping of GaN-based LEDs by quantitative infrared micro thermography. AB - A method of measuring the precise temperature distribution of GaN-based light emitting diodes (LEDs) by quantitative infrared micro-thermography is reported. To reduce the calibration error, the same measuring conditions were used for both calibration and thermal imaging; calibration was conducted on a highly emissive black-painted area on a dummy sapphire wafer loaded near the LED wafer on a thermoelectric cooler mount. We used infrared thermal radiation images of the black-painted area on the dummy wafer and an unbiased LED wafer at two different temperatures to determine the factors that degrade the accuracy of temperature measurement, i.e., the non-uniform response of the instrument, superimposed offset radiation, reflected radiation, and emissivity map of the LED surface. By correcting these factors from the measured infrared thermal radiation images of biased LEDs, we determined a precise absolute temperature image. Consequently, we could observe from where the local self-heat emerges and how it distributes on the emitting area of the LEDs. The experimental results demonstrated that highly localized self-heating and a remarkable temperature gradient, which are detrimental to LED performance and reliability, arise near the p-contact edge of the LED surface at high injection levels owing to the current crowding effect. PMID- 22666052 TI - A sensitivity-enhanced refractive index sensor using a single-mode thin-core fiber incorporating an abrupt taper. AB - A sensitivity-enhanced fiber-optic refractive index (RI) sensor based on a tapered single-mode thin-core diameter fiber is proposed and experimentally demonstrated. The sensor head is formed by splicing a section of tapered thin core diameter fiber (TCF) between two sections of single-mode fibers (SMFs). The cladding modes are excited at the first SMF-TCF interface, and then interfere with the core mode at the second interface, thus forming an inter-modal interferometer (IMI). An abrupt taper (tens of micrometers long) made by the electric-arc-heating method is utilized, and plays an important role in improving sensing sensitivity. The whole manufacture process only involves fiber splicing and tapering, and all the fabrication process can be achieved by a commercial fiber fusion splicer. Using glycerol and water mixture solution as an example, the experimental results show that the refractive index sensitivity is measured to be 0.591 nm for 1% change of surrounding RI. The proposed sensor structure features simple structure, low cost, easy fabrication, and high sensitivity. PMID- 22666053 TI - Improvement of toluene selectivity via the application of an ethanol oxidizing catalytic cell upstream of a YSZ-based sensor for air monitoring applications. AB - The sensing characteristics of a yttria-stabilized zirconia (YSZ)-based sensor utilizing a NiO sensing-electrode (SE) towards toluene (C(7)H(8)) and interfering gases (C(3)H(6), H(2), CO, NO(2) and C(2)H(5)OH) were evaluated with a view to selective C(7)H(8) monitoring in indoor atmospheres. The fabricated YSZ-based sensor showed preferential responses toward 480 ppb C(2)H(5)OH, rather than the target 50 ppb C(7)H(8) at an operational temperature of 450 degrees C under humid conditions (RH is approximately equal to 32%). To overcome this limitation, the catalytic activity of Cr(2)O(3), SnO(2), Fe(2)O(3) and NiO powders were evaluated for their selective ethanol oxidation ability. Among these oxides, SnO(2) was found to selectively oxidize C(2)H(5)OH, thus improving C(7)H(8) selectivity. An inline pre-catalytic cell loaded with SnO(2) powder was installed upstream of the YSZ-based sensor utilizing NiO-SE, which enabled the following excellent abilities by selectively catalyzing common interfering gases; sensitive ppb level detection of C(7)H(8) lower than the established Japanese Guideline value; low interferences from 50 ppb C(3)H(6), 500 ppb H(2), 100 ppb CO, 40 ppb NO(2), as well as 480 ppb C(2)H(5)OH. These operational characteristics are all indicative that the developed sensor may be suitable for real-time C(7)H(8) concentration monitoring in indoor environments. PMID- 22666054 TI - On the selection of transmission range in underwater acoustic sensor networks. AB - Transmission range plays an important role in the deployment of a practical underwater acoustic sensor network (UWSN), where sensor nodes equipping with only basic functions are deployed at random locations with no particular geometrical arrangements. The selection of the transmission range directly influences the energy efficiency and the network connectivity of such a random network. In this paper, we seek analytical modeling to investigate the tradeoff between the energy efficiency and the network connectivity through the selection of the transmission range. Our formulation offers a design guideline for energy-efficient packet transmission operation given a certain network connectivity requirement. PMID- 22666055 TI - Rao and Wald tests for nonhomogeneous scenarios. AB - In this paper, we focus on the design of adaptive receivers for nonhomogeneous scenarios. More precisely, at the design stage we assume a mismatch between the covariance matrix of the noise in the cell under test and that of secondary data. Under the above assumption, we show that the Wald test is the adaptive matched filter, while the Rao test coincides with the receiver obtained by using the Rao test design criterion in homogeneous environment, hence providing a theoretical explanation of the enhanced selectivity of this receiver. PMID- 22666051 TI - Quorum quenching revisited--from signal decays to signalling confusion. AB - In a polymicrobial community, while some bacteria are communicating with neighboring cells (quorum sensing), others are interrupting the communication (quorum quenching), thus creating a constant arms race between intercellular communication. In the past decade, numerous quorum quenching enzymes have been found and initially thought to inactivate the signalling molecules. Though this is widely accepted, the actual roles of these quorum quenching enzymes are now being uncovered. Recent evidence extends the role of quorum quenching to detoxification or metabolism of signalling molecules as food and energy source; this includes "signalling confusion", a term coined in this paper to refer to the phenomenon of non-destructive modification of signalling molecules. While quorum quenching has been explored as a novel anti-infective therapy targeting, quorum sensing evidence begins to show the development of resistance against quorum quenching. PMID- 22666056 TI - Adapting an ant colony metaphor for multi-robot chemical plume tracing. AB - We consider chemical plume tracing (CPT) in time-varying airflow environments using multiple mobile robots. The purpose of CPT is to approach a gas source with a previously unknown location in a given area. Therefore, the CPT could be considered as a dynamic optimization problem in continuous domains. The traditional ant colony optimization (ACO) algorithm has been successfully used for combinatorial optimization problems in discrete domains. To adapt the ant colony metaphor to the multi-robot CPT problem, the two-dimension continuous search area is discretized into grids and the virtual pheromone is updated according to both the gas concentration and wind information. To prevent the adapted ACO algorithm from being prematurely trapped in a local optimum, the upwind surge behavior is adopted by the robots with relatively higher gas concentration in order to explore more areas. The spiral surge (SS) algorithm is also examined for comparison. Experimental results using multiple real robots in two indoor natural ventilated airflow environments show that the proposed CPT method performs better than the SS algorithm. The simulation results for large scale advection-diffusion plume environments show that the proposed method could also work in outdoor meandering plume environments. PMID- 22666057 TI - Multiple classifier system for remote sensing image classification: a review. AB - Over the last two decades, multiple classifier system (MCS) or classifier ensemble has shown great potential to improve the accuracy and reliability of remote sensing image classification. Although there are lots of literatures covering the MCS approaches, there is a lack of a comprehensive literature review which presents an overall architecture of the basic principles and trends behind the design of remote sensing classifier ensemble. Therefore, in order to give a reference point for MCS approaches, this paper attempts to explicitly review the remote sensing implementations of MCS and proposes some modified approaches. The effectiveness of existing and improved algorithms are analyzed and evaluated by multi-source remotely sensed images, including high spatial resolution image (QuickBird), hyperspectral image (OMISII) and multi-spectral image (Landsat ETM+). Experimental results demonstrate that MCS can effectively improve the accuracy and stability of remote sensing image classification, and diversity measures play an active role for the combination of multiple classifiers. Furthermore, this survey provides a roadmap to guide future research, algorithm enhancement and facilitate knowledge accumulation of MCS in remote sensing community. PMID- 22666058 TI - Fiber optic sensor for acoustic detection of partial discharges in oil-paper insulated electrical systems. AB - A fiber optic interferometric sensor with an intrinsic transducer along a length of the fiber is presented for ultrasound measurements of the acoustic emission from partial discharges inside oil-filled power apparatus. The sensor is designed for high sensitivity measurements in a harsh electromagnetic field environment, with wide temperature changes and immersion in oil. It allows enough sensitivity for the application, for which the acoustic pressure is in the range of units of Pa at a frequency of 150 kHz. In addition, the accessibility to the sensing region is guaranteed by immune fiber-optic cables and the optical phase sensor output. The sensor design is a compact and rugged coil of fiber. In addition to a complete calibration, the in-situ results show that two types of partial discharges are measured through their acoustic emissions with the sensor immersed in oil. PMID- 22666059 TI - Nanocharacterization of soft biological samples in shear mode with quartz tuning fork probes. AB - Quartz tuning forks are extremely good resonators and their use is growing in scanning probe microscopy. Nevertheless, only a few studies on soft biological samples have been reported using these probes. In this work, we present the methodology to develop and use these nanosensors to properly work with biological samples. The working principles, fabrication and experimental setup are presented. The results in the nanocharacterization of different samples in different ambients are presented by using different working modes: amplitude modulation with and without the use of a Phase-Locked Loop (PLL) and frequency modulation. Pseudomonas aeruginosa bacteria are imaged in nitrogen using amplitude modulation. Microcontact printed antibodies are imaged in buffer using amplitude modulation with a PLL. Finally, metastatic cells are imaged in air using frequency modulation. PMID- 22666060 TI - Advances in Sensors-Centric Microprocessors and System-on-Chip. PMID- 22666061 TI - Reconfigurable routing protocol for free space optical sensor networks. AB - Recently, free space optical sensor networks (FSOSNs), which are based on free space optics (FSO) instead of radio frequency (RF), have gained increasing visibility over traditional wireless sensor networks (WSNs) due to their advantages such as larger capacity, higher security, and lower cost. However, the performance of FSOSNs is restricted to the requirement of a direct line-of-sight (LOS) path between a sender and a receiver pair. Once a node dies of energy depletion, the network would probably suffer from a dramatic decrease of connectivity, resulting in a huge loss of data packets. Thus, this paper proposes a reconfigurable routing protocol (RRP) to overcome this problem by dynamically reconfiguring the network virtual topology. The RRP works in three phases: (1) virtual topology construction, (2) routing establishment, and (3) reconfigurable routing. When data transmission begins, the data packets are first routed through the shortest hop paths. Then a reconfiguration is initiated by the node whose residual energy falls below a threshold. Nodes affected by this dying node are classified into two types, namely maintenance nodes and adjustment nodes, and they are reconfigured according to the types. An energy model is designed to evaluate the performance of RRP through OPNET simulation. Our simulation results indicate that the RRP achieves better performance compared with the simple-link protocol and a direct reconfiguration scheme in terms of connectivity, network lifetime, packet delivery ratio and the number of living nodes. PMID- 22666062 TI - Characterization of quorum sensing and quorum quenching soil bacteria isolated from Malaysian tropical montane forest. AB - We report the production and degradation of quorum sensing N-acyl-homoserine lactones by bacteria isolated from Malaysian montane forest soil. Phylogenetic analysis indicated that these isolates clustered closely to the genera of Arthrobacter, Bacillus and Pseudomonas. Quorum quenching activity was detected in six isolates of these three genera by using a series of bioassays and rapid resolution liquid chromatography analysis. Biosensor screening and high resolution liquid chromatography-mass spectrometry analysis revealed the production of N-dodecanoyl-L-homoserine lactone (C12-HSL) by Pseudomonas frederiksbergensis (isolate BT9). In addition to degradation of a wide range of N acyl-homoserine lactones, Arthrobacter and Pseudomonas spp. also degraded p coumaroyl-homoserine lactone. To the best of our knowledge, this is the first documentation of Arthrobacter and Pseudomonas spp. capable of degrading p coumaroyl-homoserine lactone and the production of C12-HSL by P. frederiksbergensis. PMID- 22666063 TI - Facile one-step microwave-assisted route towards Ni nanospheres/reduced graphene oxide hybrids for non-enzymatic glucose sensing. AB - In this work, a facile one-step microwave-assisted method for deposition of monodisperse Ni nanospheres on reduced graphene oxide (rGO) sheets to form Ni-rGO nanohybrids is discussed. In the presence of hydrazine monohydrate, Ni nanospheres are grown onto rGO sheets using nickel precursor and GO as starting materials in ethylene glycol (EG) solution under a low level of microwave irradiation (300 W) for 20 min, during which GO is also reduced to rGO. The as prepared nanohybrids exhibit well-dispersed Ni nanosphere (about 80 nm in diameter) loadings and effective reduction of graphene oxide. The resulting Ni rGO nanohybrids-modified glassy carbon electrode (GCE) shows significantly improved electrochemical performance in nonenzymatic amperometric glucose detection. In addition, interference from the oxidation of common interfering species under physiological conditions, such as ascorbic acid (AA) and uric acid (UA), is effectively avoided. PMID- 22666064 TI - Transformation of ground vibration signal for debris-flow monitoring and detection in alarm systems. AB - Debris flows are fast mass movements formed by a mix of water and solid materials, which occur in steep torrents, and are a source of high risks for human settlements. Geophones are widely used to detect the ground vibration induced by passing debris flows. However, the recording of geophone signals usually requires storing a huge amount of data, which leads to problems in storage capacity and power consumption. This paper presents a method to transform and simplify the signals measured by geophones. The key input parameter is the ground velocity threshold, which removes the seismic noise that is not related to debris flows. A signal conditioner was developed to implement the transformation and the ground velocity threshold was set by electrical resistors. The signal conditioner was installed at various European monitoring sites to test the method. Results show that data amount and power consumption can be greatly reduced without losing much information on the main features of the debris flows. However, the outcome stresses the importance of choosing a ground vibration threshold, which must be accurately calibrated. The transformation is also suitable to detect other rapid mass movements and to distinguish among different processes, which points to a possible implementation in alarm systems. PMID- 22666065 TI - Sensors in collaboration increase individual potentialities. PMID- 22666066 TI - Modelling of amperometric biosensor used for synergistic substrates determination. AB - In this paper the operation of an amperometric biosensor producing a chemically amplified signal is modelled numerically. The chemical amplification is achieved by using synergistic substrates. The model is based on non-stationary reaction diffusion equations. The model involves three layers (compartments): a layer of enzyme solution entrapped on the electrode surface, a dialysis membrane covering the enzyme layer and an outer diffusion layer which is modelled by the Nernst approach. The equation system is solved numerically by using the finite difference technique. The biosensor response and sensitivity are investigated by altering the model parameters influencing the enzyme kinetics as well as the mass transport by diffusion. The biosensor action was analyzed with a special emphasis to the effect of the chemical amplification. The simulation results qualitatively explain and confirm the experimentally observed effect of the synergistic substrates conversion on the biosensor response. PMID- 22666067 TI - A new methodology for vibration error compensation of optical encoders. AB - Optical encoders are sensors based on grating interference patterns. Tolerances inherent to the manufacturing process can induce errors in the position accuracy as the measurement signals stand apart from the ideal conditions. In case the encoder is working under vibrations, the oscillating movement of the scanning head is registered by the encoder system as a displacement, introducing an error into the counter to be added up to graduation, system and installation errors. Behavior improvement can be based on different techniques trying to compensate the error from measurement signals processing. In this work a new "ad hoc" methodology is presented to compensate the error of the encoder when is working under the influence of vibration. The methodology is based on fitting techniques to the Lissajous figure of the deteriorated measurement signals and the use of a look up table, giving as a result a compensation procedure in which a higher accuracy of the sensor is obtained. PMID- 22666068 TI - Assessing ambiguity of context data in intelligent environments: towards a more reliable context managing system. AB - Modeling and managing correctly the user context in Smart Environments is important to achieve robust and reliable systems. When modeling reality we must take into account its ambiguous nature. Considering the uncertainty and vagueness in context data information it is possible to attain a more precise picture of the environment, thus leading to a more accurate inference process. To achieve these goals we present an ontology that models the ambiguity in intelligent environments and a data fusion and inference process that takes advantage of that extra information to provide better results. Our system can assess the certainty of the captured measurements, discarding the unreliable ones and combining the rest into a unified vision of the current user context. It also models the vagueness of the system, combining it with the uncertainty to obtain a richer inference process. PMID- 22666069 TI - Gold nanoparticles functionalized with peptides for specific affinity aggregation assays of estrogen receptors and their agonists. AB - Nuclear receptors regulate the transcription of genes and various functions such as development, differentiation, homeostasis, and behavior by formation of complexes with ligand and co-activator. Recent findings have shown that agonists of a ligand may have a toxic effect on cellular/tissular function through improper activation of nuclear receptors. In this study, a simple assay system of hetero-complexes of three different molecules (estrogen receptor, ligand, and co activator peptide) has been developed. This assay system employs functionalized gold nanoparticles (GNPs: 15 nm in diameter). The surfaces of the GNPs were modified by a 12- or 20-amino-acid peptide that contains the sequence of co activator for activating nuclear receptor by an agonist ligand. Owing to the affinity of the peptide, the functionalized GNPs aggregate faster when the nuclear receptor and the agonist ligand are also present. The aggregation of GNPs can be identified by shifts in adsorption spectrum, which give information about the specificity of agonist ligands. Similarly, this spectrum shift can measure concentration of known agonist ligand. This simple agonist screening will be employed as high through-put analysis (HTA) in the discovery of drugs that act through nuclear receptors. PMID- 22666070 TI - Dynamic sensing of localized corrosion at the metal/solution interface. AB - A Mach-Zehnder interferometer is employed to detect localized corrosion at the metal/solution interface in the potentiodynamic sweep of the iron electrode in solutions. During the electrochemical reactions, local variations of the electrolyte's refractive index, which correlate with the concentration of dissolved species, change the optical path length (OPL) of the object beam when the beam passes through the electrolyte. The distribution of the OPL difference was obtained to present the concentration change of the metal ions visually, which enable direct evidence of corrosion processes. The OPL difference distribution shows localized and general corrosion during the anodic dissolution of the iron electrode in solutions with and without chloride ions, respectively. This method provides an approach for dynamic detection of localized corrosion at the metal/solution interface. PMID- 22666072 TI - Simulation and experimental investigation of structural dynamic frequency characteristics control. AB - In general, mechanical equipment such as cars, airplanes, and machine tools all operate with constant frequency characteristics. These constant working characteristics should be controlled if the dynamic performance of the equipment demands improvement or the dynamic characteristics is intended to change with different working conditions. Active control is a stable and beneficial method for this, but current active control methods mainly focus on vibration control for reducing the vibration amplitudes in the time domain or frequency domain. In this paper, a new method of dynamic frequency characteristics active control (DFCAC) is presented for a flat plate, which can not only accomplish vibration control but also arbitrarily change the dynamic characteristics of the equipment. The proposed DFCAC algorithm is based on a neural network including two parts of the identification implement and the controller. The effectiveness of the DFCAC method is verified by several simulation and experiments, which provide desirable results. PMID- 22666071 TI - Endogenous bioactive peptides as potential biomarkers for atherosclerotic coronary heart disease. AB - Cardiovascular disease is the leading cause of death worldwide, with high medical costs and rates of disability. It is therefore important to evaluate the use of cardiovascular biomarkers in the early diagnosis of coronary artery disease (CAD). We have screened a variety of recently identified bioactive peptides candidates in anticipation that they would allow detection of atherosclerotic CAD. Especially, we have focused on novel anti-atherogenic peptides as indicators and negative risk factors for CAD. In vitro, in vivo and clinical studies indicated that human adiponectin, heregulin-beta(1), glucagon-like peptide-1 (GLP 1), and salusin-alpha, peptides of 244, 71, 30, and 28 amino acids, respectively, attenuate the development and progression of atherosclerotic lesions by suppressing macrophage foam cell formation via down-regulation of acyl-coenzyme A: cholesterol acyltransferase-1. Circulating levels of these peptides in the blood are significantly decreased in patients with CAD compared to patients without CAD. Receiver operating characteristic analyses showed that salusin-alpha is a more useful biomarker, with better sensitivity and specificity, compared with the others for detecting CAD. Therefore, salusin-alpha, heregulin-beta(1), adiponectin, and/or GLP-1, alone or in various combinations, may be useful as biomarkers for atherosclerotic CAD. PMID- 22666074 TI - Penalty dynamic programming algorithm for dim targets detection in sensor systems. AB - In order to detect and track multiple maneuvering dim targets in sensor systems, an improved dynamic programming track-before-detect algorithm (DP-TBD) called penalty DP-TBD (PDP-TBD) is proposed. The performances of tracking techniques are used as a feedback to the detection part. The feedback is constructed by a penalty term in the merit function, and the penalty term is a function of the possible target state estimation, which can be obtained by the tracking methods. With this feedback, the algorithm combines traditional tracking techniques with DP-TBD and it can be applied to simultaneously detect and track maneuvering dim targets. Meanwhile, a reasonable constraint that a sensor measurement can originate from one target or clutter is proposed to minimize track separation. Thus, the algorithm can be used in the multi-target situation with unknown target numbers. The efficiency and advantages of PDP-TBD compared with two existing methods are demonstrated by several simulations. PMID- 22666075 TI - Identification of cross-country skiing movement patterns using micro-sensors. AB - This study investigated the potential of micro-sensors for use in the identification of the main movement patterns used in cross-country skiing. Data were collected from four elite international and four Australian athletes in Europe and in Australia using a MinimaxXTM unit containing accelerometer, gyroscope and GPS sensors. Athletes performed four skating techniques and three classical techniques on snow at moderate velocity. Data from a single micro sensor unit positioned in the centre of the upper back was sufficient to visually identify cyclical movement patterns for each technique. The general patterns for each technique were identified clearly across all athletes while at the same time distinctive characteristics for individual athletes were observed. Differences in speed, snow condition and gradient of terrain were not controlled in this study and these factors could have an effect on the data patterns. Development of algorithms to process the micro-sensor data into kinematic measurements would provide coaches and scientists with a valuable performance analysis tool. Further research is needed to develop such algorithms and to determine whether the patterns are consistent across a range of different speeds, snow conditions and terrain, and for skiers of differing ability. PMID- 22666073 TI - Visualizing sweetness: increasingly diverse applications for fluorescent-tagged glucose bioprobes and their recent structural modifications. AB - Glucose homeostasis is a fundamental aspect of life and its dysregulation is associated with important diseases, such as cancer and diabetes. Traditionally, glucose radioisotopes have been used to monitor glucose utilization in biological systems. Fluorescent-tagged glucose analogues were initially developed in the 1980s, but it is only in the past decade that their use as a glucose sensor has increased significantly. These analogues were developed for monitoring glucose uptake in blood cells, but their recent applications include tracking glucose uptake by tumor cells and imaging brain cell metabolism. This review outlines the development of fluorescent-tagged glucose analogues, describes their recent structural modifications and discusses their increasingly diverse biological applications. PMID- 22666076 TI - Performance analyses and improvements for the IEEE 802.15.4 CSMA/CA scheme with heterogeneous buffered conditions. AB - Studies of the IEEE 802.15.4 Carrier Sense Multiple Access with Collision Avoidance (CSMA/CA) scheme have been received considerable attention recently, with most of these studies focusing on homogeneous or saturated traffic. Two novel transmission schemes-OSTS/BSTS (One Service a Time Scheme/Bulk Service a Time Scheme)-are proposed in this paper to improve the behaviors of time-critical buffered networks with heterogeneous unsaturated traffic. First, we propose a model which contains two modified semi-Markov chains and a macro-Markov chain combined with the theory of M/G/1/K queues to evaluate the characteristics of these two improved CSMA/CA schemes, in which traffic arrivals and accessing packets are bestowed with non-preemptive priority over each other, instead of prioritization. Then, throughput, packet delay and energy consumption of unsaturated, unacknowledged IEEE 802.15.4 beacon-enabled networks are predicted based on the overall point of view which takes the dependent interactions of different types of nodes into account. Moreover, performance comparisons of these two schemes with other non-priority schemes are also proposed. Analysis and simulation results show that delay and fairness of our schemes are superior to those of other schemes, while throughput and energy efficiency are superior to others in more heterogeneous situations. Comprehensive simulations demonstrate that the analysis results of these models match well with the simulation results. PMID- 22666077 TI - Humidity-induced charge leakage and field attenuation in electric field microsensors. AB - The steady-state zero output of static electric field measuring systems often fluctuates, which is caused mainly by the finite leakage resistance of the water film on the surface of the electric field microsensor package. The water adsorption has been calculated using the Boltzmann distribution equation at various relative humidities for borosilicate glass and polytetrafluoroethylene surfaces. At various humidities, water film thickness has been calculated, and the induced charge leakage and field attenuation have been theoretically investigated. Experiments have been performed with microsensors to verify the theoretical predictions and the results are in good agreement. PMID- 22666078 TI - Method for optimal sensor deployment on 3D terrains utilizing a steady state genetic algorithm with a guided walk mutation operator based on the wavelet transform. AB - One of the most critical issues of Wireless Sensor Networks (WSNs) is the deployment of a limited number of sensors in order to achieve maximum coverage on a terrain. The optimal sensor deployment which enables one to minimize the consumed energy, communication time and manpower for the maintenance of the network has attracted interest with the increased number of studies conducted on the subject in the last decade. Most of the studies in the literature today are proposed for two dimensional (2D) surfaces; however, real world sensor deployments often arise on three dimensional (3D) environments. In this paper, a guided wavelet transform (WT) based deployment strategy (WTDS) for 3D terrains, in which the sensor movements are carried out within the mutation phase of the genetic algorithms (GAs) is proposed. The proposed algorithm aims to maximize the Quality of Coverage (QoC) of a WSN via deploying a limited number of sensors on a 3D surface by utilizing a probabilistic sensing model and the Bresenham's line of sight (LOS) algorithm. In addition, the method followed in this paper is novel to the literature and the performance of the proposed algorithm is compared with the Delaunay Triangulation (DT) method as well as a standard genetic algorithm based method and the results reveal that the proposed method is a more powerful and more successful method for sensor deployment on 3D terrains. PMID- 22666079 TI - Benefits of combined GPS/GLONASS with low-cost MEMS IMUs for vehicular urban navigation. AB - The integration of Global Navigation Satellite Systems (GNSS) with Inertial Navigation Systems (INS) has been very actively researched for many years due to the complementary nature of the two systems. In particular, during the last few years the integration with micro-electromechanical system (MEMS) inertial measurement units (IMUs) has been investigated. In fact, recent advances in MEMS technology have made possible the development of a new generation of low cost inertial sensors characterized by small size and light weight, which represents an attractive option for mass-market applications such as vehicular and pedestrian navigation. However, whereas there has been much interest in the integration of GPS with a MEMS-based INS, few research studies have been conducted on expanding this application to the revitalized GLONASS system. This paper looks at the benefits of adding GLONASS to existing GPS/INS(MEMS) systems using loose and tight integration strategies. The relative benefits of various constraints are also assessed. Results show that when satellite visibility is poor (approximately 50% solution availability) the benefits of GLONASS are only seen with tight integration algorithms. For more benign environments, a loosely coupled GPS/GLONASS/INS system offers performance comparable to that of a tightly coupled GPS/INS system, but with reduced complexity and development time. PMID- 22666080 TI - HPV-associated head and neck cancer: molecular and nano-scale markers for prognosis and therapeutic stratification. AB - Over the last 10 years, it has become clear that patients with head and neck cancer can be stratified into two distinct subgroups on the basis of the etiology of their disease. Patients with human papillomavirus-related cancers have significantly better survival rates and may necessitate different therapeutic approaches than those with tobacco and/or alcohol related cancers. This review discusses the various biomarkers currently in use for identification of patients with HPV-positive cancers with a focus on the advantages and limitations of molecular and nano-scale markers. PMID- 22666081 TI - Exploitation of unique properties of zeolites in the development of gas sensors. AB - The unique properties of microporous zeolites, including ion-exchange properties, adsorption, molecular sieving, catalysis, conductivity have been exploited in improving the performance of gas sensors. Zeolites have been employed as physical and chemical filters to improve the sensitivity and selectivity of gas sensors. In addition, direct interaction of gas molecules with the extraframework cations in the nanoconfined space of zeolites has been explored as a basis for developing new impedance-type gas/vapor sensors. In this review, we summarize how these properties of zeolites have been used to develop new sensing paradigms. There is a considerable breadth of transduction processes that have been used for zeolite incorporated sensors, including frequency measurements, optical and the entire gamut of electrochemical measurements. It is clear from the published literature that zeolites provide a route to enhance sensor performance, and it is expected that commercial manifestation of some of the approaches discussed here will take place. The future of zeolite-based sensors will continue to exploit its unique properties and use of other microporous frameworks, including metal organic frameworks. Zeolite composites with electronic materials, including metals will lead to new paradigms in sensing. Use of nano-sized zeolite crystals and zeolite membranes will enhance sensor properties and make possible new routes of miniaturized sensors. PMID- 22666082 TI - Identification of the major expressed S-layer and cell surface-layer-related proteins in the model methanogenic archaea: Methanosarcina barkeri Fusaro and Methanosarcina acetivorans C2A. AB - Many archaeal cell envelopes contain a protein coat or sheath composed of one or more surface exposed proteins. These surface layer (S-layer) proteins contribute structural integrity and protect the lipid membrane from environmental challenges. To explore the species diversity of these layers in the Methanosarcinaceae, the major S-layer protein in Methanosarcina barkeri strain Fusaro was identified using proteomics. The Mbar_A1758 gene product was present in multiple forms with apparent sizes of 130, 120, and 100 kDa, consistent with post-translational modifications including signal peptide excision and protein glycosylation. A protein with features related to the surface layer proteins found in Methanosarcina acetivorans C2A and Methanosarcina mazei Goel was identified in the M. barkeri genome. These data reveal a distinct conserved protein signature with features and implied cell surface architecture in the Methanosarcinaceae that is absent in other archaea. Paralogous gene expression patterns in two Methanosarcina species revealed abundant expression of a single S layer paralog in each strain. Respective promoter elements were identified and shown to be conserved in mRNA coding and upstream untranslated regions. Prior M. acetivorans genome annotations assigned S-layer or surface layer associated roles of eighty genes: however, of 68 examined none was significantly expressed relative to the experimentally determined S-layer gene. PMID- 22666083 TI - Versatility of RNA-Binding Proteins in Cancer. AB - Posttranscriptional gene regulation is a rapid and efficient process to adjust the proteome of a cell to a changing environment. RNA-binding proteins (RBPs) are the master regulators of mRNA processing and translation and are often aberrantly expressed in cancer. In addition to well-studied transcription factors, RBPs are emerging as fundamental players in tumor development. RBPs and their mRNA targets form a complex network that plays a crucial role in tumorigenesis. This paper describes mechanisms by which RBPs influence the expression of well-known oncogenes, focusing on precise examples that illustrate the versatility of RBPs in posttranscriptional control of cancer development. RBPs appeared very early in evolution, and new RNA-binding domains and combinations of them were generated in more complex organisms. The identification of RBPs, their mRNA targets, and their mechanism of action have provided novel potential targets for cancer therapy. PMID- 22666085 TI - Repertoire of Protein Kinases Encoded in the Genome of Takifugu rubripes. AB - Takifugu rubripes is teleost fish widely used in comparative genomics to understand the human system better due to its similarities both in number of genes and structure of genes. In this work we survey the fugu genome, and, using sensitive computational approaches, we identify the repertoire of putative protein kinases and classify them into groups and subfamilies. The fugu genome encodes 519 protein kinase-like sequences and this number of putative protein kinases is comparable closely to that of human. However, in spite of its similarities to human kinases at the group level, there are differences at the subfamily level as noted in the case of KIS and DYRK subfamilies which contribute to differences which are specific to the adaptation of the organism. Also, certain unique domain combination of galectin domain and YkA domain suggests alternate mechanisms for immune response and binding to lipoproteins. Lastly, an overall similarity with the MAPK pathway of humans suggests its importance to understand signaling mechanisms in humans. Overall the fugu serves as a good model organism to understand roles of human kinases as far as kinases such as LRRK and IRAK and their associated pathways are concerned. PMID- 22666084 TI - On the Diversification of the Translation Apparatus across Eukaryotes. AB - Diversity is one of the most remarkable features of living organisms. Current assessments of eukaryote biodiversity reaches 1.5 million species, but the true figure could be several times that number. Diversity is ingrained in all stages and echelons of life, namely, the occupancy of ecological niches, behavioral patterns, body plans and organismal complexity, as well as metabolic needs and genetics. In this review, we will discuss that diversity also exists in a key biochemical process, translation, across eukaryotes. Translation is a fundamental process for all forms of life, and the basic components and mechanisms of translation in eukaryotes have been largely established upon the study of traditional, so-called model organisms. By using modern genome-wide, high throughput technologies, recent studies of many nonmodel eukaryotes have unveiled a surprising diversity in the configuration of the translation apparatus across eukaryotes, showing that this apparatus is far from being evolutionarily static. For some of the components of this machinery, functional differences between different species have also been found. The recent research reviewed in this article highlights the molecular and functional diversification the translational machinery has undergone during eukaryotic evolution. A better understanding of all aspects of organismal diversity is key to a more profound knowledge of life. PMID- 22666087 TI - Human Genomic Deletions Generated by SVA-Associated Events. AB - Mobile elements are responsible for half of the human genome. Among the elements, L1 and Alu are most ubiquitous. They use L1 enzymatic machinery to move in their host genomes. A significant amount of research has been conducted about these two elements. The results showed that these two elements have played important roles in generating genomic variations between human and chimpanzee lineages and even within a species, through various mechanisms. SVA elements are a third type of mobile element which uses the L1 enzymatic machinery to propagate in the human genome but has not been studied much relative to the other elements. Here, we attempt the first identification of the human genomic deletions caused by SVA elements, through the comparison of human and chimpanzee genome sequences. We identified 13 SVA recombination-associated deletions (SRADs) and 13 SVA insertion mediated deletions (SIMDs) in the human genome and characterized them, focusing on deletion size and the mechanisms causing the events. The results showed that the SRADs and SIMDs have deleted 15,752 and 30,785 bp, respectively, in the human genome since the divergence of human and chimpanzee and that SRADs were caused by two different mechanisms, nonhomologous end joining and nonallelic homologous recombination. PMID- 22666088 TI - Local delivery of growth factors using coated suture material. AB - The optimization of healing processes in a wide range of tissues represents a central point for surgical research. One approach is to stimulate healing processes with growth factors. These substances have a short half-life and therefore it seems useful to administer these substances locally rather than systemically. One possible method of local delivery is to incorporate growth factors into a bioabsorbable poly (D, L-lactide) suspension (PDLLA) and coat suture material. The aim of the present study was to establish a procedure for the local delivery of growth factors using coated suture material. Sutures coated with growth factors were tested in an animal model. Anastomoses of the colon were created in a rat model using monofilament sutures. These were either untreated or coated with PDLLA coating alone or coated with PDLLA incorporating insulin-like growth factor-I (IGF-I). The anastomoses were subjected to biomechanical, histological, and immunohistochemical examination. After 3 days the treated groups showed a significantly greater capacity to withstand biomechanical stress than the control groups. This finding was supported by the results of the histomorphometric. The results of the study indicate that it is possible to deliver bioactive growth factors locally using PDLLA coated suture material. Healing processes can thus be stimulated locally without subjecting the whole organism to potentially damaging high systemic doses. PMID- 22666086 TI - Conservation of the RNA Transport Machineries and Their Coupling to Translation Control across Eukaryotes. AB - Restriction of proteins to discrete subcellular regions is a common mechanism to establish cellular asymmetries and depends on a coordinated program of mRNA localization and translation control. Many processes from the budding of a yeast to the establishment of metazoan embryonic axes and the migration of human neurons, depend on this type of cell polarization. How factors controlling transport and translation assemble to regulate at the same time the movement and translation of transported mRNAs, and whether these mechanisms are conserved across kingdoms is not yet entirely understood. In this review we will focus on some of the best characterized examples of mRNA transport machineries, the "yeast locasome" as an example of RNA transport and translation control in unicellular eukaryotes, and on the Drosophila Bic-D/Egl/Dyn RNA localization machinery as an example of RNA transport in higher eukaryotes. This focus is motivated by the relatively advanced knowledge about the proteins that connect the localizing mRNAs to the transport motors and the many well studied proteins involved in translational control of specific transcripts that are moved by these machineries. We will also discuss whether the core of these RNA transport machineries and factors regulating mRNA localization and translation are conserved across eukaryotes. PMID- 22666089 TI - Toxicity of metals to a freshwater snail, Melanoides tuberculata. AB - Adult freshwater snails Melanoides tuberculata (Gastropod, Thiaridae) were exposed for a four-day period in laboratory conditions to a range of copper (Cu), cadmium (Cd), zinc (Zn), lead (Pb), nickel (Ni), iron (Fe), aluminium (Al), and manganese (Mn) concentrations. Mortality was assessed and median lethal times (LT50) and concentrations (LC50) were calculated. LT50 and LC50 increased with the decrease in mean exposure concentrations and times, respectively, for all metals. The LC(50) values for the 96-hour exposures to Cu, Cd, Zn, Pb, Ni, Fe, Al, and Mn were 0.14, 1.49, 3.90, 6.82, 8.46, 8.49, 68.23, and 45.59 mg L-1, respectively. Cu was the most toxic metal to M. tuberculata, followed by Cd, Zn, Pb, Ni, Fe, Mn, and Al (Cu > Cd > Zn > Pb > Ni > Fe > Mn > Al). Metals bioconcentration in M. tuberculata increases with exposure to increasing concentrations and Cu has the highest accumulation (concentration factor) in the soft tissues. A comparison of LC50 values for metals for this species with those for other freshwater gastropods reveals that M. tuberculata is equally sensitive to metals. PMID- 22666090 TI - Association of Acinetobacter baumannii EF-Tu with cell surface, outer membrane vesicles, and fibronectin. AB - A conundrum has long lingered over association of cytosol elongation factor Tu (EF-Tu) with bacterial surface. Here we investigated it with Acinetobacter baumannii, an emerging opportunistic pathogen associated with a wide spectrum of infectious diseases. The gene for A. baumannii EF-Tu was sequenced, and recombinant EF-Tu was purified for antibody development. EF-Tu on the bacterial surface and the outer membrane vesicles (OMVs) was revealed by immune electron microscopy, and its presence in the outer membrane (OM) and the OMV subproteomes was verified by Western blotting with the EF-Tu antibodies and confirmed by proteomic analyses. EF-Tu in the OM and the OMV subproteomes bound to fibronectin as detected by Western blot and confirmed by a label-free real-time optical sensor. The sensor that originates from photonic crystal structure in a total Internal-reflection (PC-TIR) configuration was functionalized with fibronectin for characterizing EF-Tu binding. Altogether, with a novel combination of immunological, proteomical, and biophysical assays, these results suggest association of A. baumannii EF-Tu with the bacterial cell surface, OMVs, and fibronectin. PMID- 22666091 TI - Interim evaluation of the project P.A.T.H.S.: findings based on different datasets. AB - Interim evaluation studies were carried out in order to examine the implementation details of the Tier 1 Program of the Project P.A.T.H.S. (Positive Adolescent Training through Holistic Social Programmes) in Hong Kong. Quantitative results of the interim evaluation findings based on eight datasets collected from 2006 to 2009 are reported in this paper. Three hundred and seventy eight schools were randomly selected to provide information on the implementation details of the program via face-to-face interviews, telephone interviews, and self-completed questionnaires. Results showed that a majority of the workers perceived that the students had positive responses to the program and the program was helpful to the students. In conjunction with other process evaluation findings, the present study suggests that the implementation quality of the Tier 1 Program of the Project P.A.T.H.S. is high. The present study also provides support for the effectiveness of the Tier 1 Program of the Project P.A.T.H.S. in Hong Kong. PMID- 22666092 TI - Leishmanicidal activity of nine novel flavonoids from Delphinium staphisagria. AB - OBJECTIVES: To evaluate the in vitro leishmanicidal activity of nine flavonoid derivatives from Delphinium staphisagria against L. infantum and L. braziliensis. DESIGN AND METHODS: The in vitro activity of compounds 1-9 was assayed on extracellular promastigote and axenic amastigote forms and on intracellular amastigote forms of the parasites. Infectivity and cytotoxicity tests were carried on J774.2 macrophage cells using Glucantime as the reference drug. The mechanisms of action were analysed performing metabolite excretion and transmission electronic microscope ultrastructural alteration studies. RESULTS: Nine flavonoids showed leishmanicidal activity against promastigote as well as amastigote forms of Leishmania infantum and L. braziliensis. These compounds were nontoxic to mammalian cells and were effective at similar concentrations up to or lower than that of the reference drug (Glucantime). The results showed that 2(") acetylpetiolaroside (compound 8) was clearly the most active. CONCLUSION: This study has demonstrated that flavonoid derivatives are active against L. infantum and L. braziliensis. PMID- 22666094 TI - Ground wheat grain for midlactation cows: challenging a common wisdom. AB - The objective was to determine the effects of ground wheat grain (GW) inclusion rate, grinding extent (GE), and their interaction on lactating cow performance. Eight midlactation cows in 3 * 4 m individual boxes were used in a 4 * 4 replicated Latin square design study with 4 21 d periods. GW was fed at either 10% or 20% of diet dry matter (DM), as either finer or coarser particles. DM intake increased and net energy for lactation (NE(L)) intake tended to increase when GW was fed at 10% instead of 20% of diet DM. Milk energy yield, milk solids content and yield, and urine pH were unaffected. Fecal pH tended to increase at 20% versus 10% GW. Total tract apparent NDF, but not DM, digestibility tended to be greater for coarsely than finely GW and tended to be greater at 10% versus 20% GW. GW at 10% versus 20% of diet DM decreased blood BHBA and increased blood concentrations of total proteins and albumin. Data provide novel evidence that both finely and coarsely ground WG can be safely fed up to 20% midlactation cows. Commercial accessibility and cost will determine feeding preference of wheat grain to dairy cows. PMID- 22666093 TI - Protection of the extracts of Lentinus edodes mycelia against carbon tetrachloride-induced hepatic injury in rats. AB - Lentinus edodes is the medicinal macrofungus showing potential for therapeutic applications in infectious disorders including hepatitis. In an attempt to develop the agent for handling hepatic injury, we used the extracts of Lentinus edodes mycelia (LEM) to screen the effect on hepatic injury in rats induced by carbon tetrachloride (CCl4). Intraperitoneal administration of CCl4 not only increased plasma glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) but also decreased hepatic superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels in rats. Similar to the positive control silymarin, oral administration (three times daily) of this product (LEM) for 8 weeks significantly reduced plasma GOT and GPT. Also, the activities of antioxidant enzymes of SOD and GPx were elevated by LEM. in liver from CCl4 treated rats, indicating that mycelium can increase antioxidant-like activity. Moreover, the hepatic mRNA and protein levels of SOD and GPx were both markedly raised by LEM. The obtained results suggest that oral administration of the extracts of Lentinus edodes mycelia (LEM) has the protective effect against CCl4 induced hepatic injury in rats, mainly due to an increase in antioxidant-like action. PMID- 22666095 TI - Activation of beta-adrenoceptors by dobutamine may induce a higher expression of peroxisome proliferator-activated receptors delta (PPARdelta) in neonatal rat cardiomyocytes. AB - Recent evidence showed the role of peroxisome proliferator-activated receptors (PPARs) in cardiac function. Cardiac contraction induced by various agents is critical in restoring the activity of peroxisome proliferator-activated receptors delta (PPARdelta) in cardiac myopathy. Because dobutamine is an agent widely used to treat heart failure in emergency setting, this study is aimed to investigate the change of PPARdelta in response to dobutamine. Neonatal rat cardiomyocytes were used to examine the effects of dobutamine on PPARdelta expression levels and cardiac troponin I (cTnI) phosphorylation via Western blotting analysis. We show that treatment with dobutamine increased PPARdelta expression and cTnI phosphorylation in a time- and dose-dependent manner in neonatal rat cardiomyocytes. These increases were blocked by the antagonist of beta1 adrenoceptors. Also, the action of dobutamine was related to the increase of calcium ions and diminished by chelating intracellular calcium. Additionally, dobutamine-induced action was reduced by the inhibition of downstream messengers involved in this calcium-related pathway. Moreover, deletion of PPARdelta using siRNA generated the reduction of cTnI phosphorylation in cardiomyocytes treated with dobutamine. Thus, we concluded that PPARdelta is increased by dobutamine in cardiac cells. PMID- 22666097 TI - The role of biotechnology for conservation and biologically active substances production of Rhodiola rosea: endangered medicinal species. AB - At present, more than 50,000 plant species are used in phytotherapy and medicine. About 2/3 of them are harvested from nature leading to local extinction of many species or degradation of their habitats. Biotechnological methods offer possibilities not only for faster cloning and conservation of the genotype of the plants but for modification of their gene information, regulation, and expression for production of valuable substances in higher amounts or with better properties. Rhodiola rosea is an endangered medicinal species with limited distribution. It has outstanding importance for pharmaceutical industry for prevention and cure of cancer, heart and nervous system diseases, and so forth. Despite the great interest in golden root and the wide investigations in the area of phytochemistry, plant biotechnology remained less endeavoured and exploited. The paper presents research on initiation of in vitro cultures in Rhodiola rosea and some other Rhodiola species. Achievements in induction of organogenic and callus cultures, regeneration, and micropropagation varied but were a good basis for alternative in vitro synthesis of the desired metabolites and for the development of efficient systems for micropropagation for conservation of the species. PMID- 22666096 TI - Impact of a preemptive multimodal analgesia plus femoral nerve blockade protocol on rehabilitation, hospital length of stay, and postoperative analgesia after primary total knee arthroplasty: a controlled clinical pilot study. AB - PURPOSE: To compare preemptive multimodal analgesia (PMMA) without femoral nerve blocks (FNB) to PMMA including FNB following total knee arthroplasty (TKA). METHODS: In a prospective, controlled pilot study, subjects with noninflammatory arthritis undergoing TKA and a short postoperative stay received either PMMA + FNB (FNB group; n = 19) or PMMA only (PMMA group; n = 20). No preoperative group differences were noted. Evaluations occurred in hospital and at 2, 6, and 12 weeks postoperatively. The primary outcome (knee flexion) was measured on day two postoperatively. Rehabilitation indices, pain, analgesic use, and length of stay (LOS) were also measured. RESULTS: All subjects completed the study. The only significant group differences were quadriceps motor blocks in the FNB group (P < 0.001). No significant differences were noted in ROM, pain levels, analgesic use, or hospital LOS. CONCLUSION: Other than the quadriceps motor block, no group differences were noted; both achieved satisfactory analgesia. Best postoperative pain management strategies when following a short hospital stay program are still unclear. PMID- 22666098 TI - Changes in cardiac tone regulation with fatigue after supra-maximal running exercise. AB - To investigate the effects of fatigue and metabolite accumulation on the postexercicse parasympathetic reactivation, 11 long-sprint runners performed on an outdoor track an exhaustive 400 m long sprint event and a 300 m with the same 400 m pacing strategy. Time constant of heart rate recovery (HRRtau), time (RMSSD), and frequency (HF, and LF) varying vagal-related heart rate variability indexes were assessed during the 7 min period immediately following exercise. Biochemical parameters (blood lactate, pH, PO2, PCO2, SaO2, and HCO3-) were measured at 1, 4 and 7 min after exercise. Time to perform 300 m was not significantly different between both running trials. HHRtau measured after the 400 m running exercise was longer compared to 300 m running bouts (183.7 +/- 11.6 versus 132.1 +/- 9.8 s, P < 0.01). Absolute power density in the LF and HF bands was also lower after 400 m compared to the 300 m trial (P < 0.05). No correlation was found between biochemical and cardiac recovery responses except for the PO2 values which were significantly correlated with HF levels measured 4 min after both bouts. Thus, it appears that fatigue rather than metabolic stresses occurring during a supramaximal exercise could explain the delayed postexercise parasympathetic reactivation in longer sprint runs. PMID- 22666099 TI - Is the goat a new host for the G3 Indian buffalo strain of Echinococcus granulosus? AB - Four goats bred in Central Italy (province of Rieti) revealed, in the liver, metacestodes of Echinococcus granulosus. The cysts, unilocular and fertile, were examined by microscopy and molecular diagnostics. Morphological data on the rostellar hooks are in agreement with the original description of the strain found in buffaloes and are largely compatible with those reported in Europe for cattle and humans. Specific PCR followed by DNA sequencing of the mitochondrial cox1 gene revealed for all the isolates 99.5% identity to the reference strain G3 genotype and 99.3% and 99.1% to G2 and G1, respectively. Further genetic markers (nad1 and 12S rRNA) confirmed the identity of the goat isolates to the G3 strain. This genotype, here reported for the first time in goats, proved to have a wider than previously supposed host range, therefore its relevance in human hydatidosis is expected to be more often evidenced. PMID- 22666100 TI - Social networking sites and educational adaptation in higher education: a case study of Chinese international students in New Zealand. AB - This study aims to find out the relationship between the use of SNSs and educational adaptation process of Chinese international students (from China) in New Zealand. Based on interview data, this paper addressed how Chinese international students use SNSs (RenRen, Facebook, etc.) to expand and manage their online social networks to help their adaptation to new educational environment. As a case study of Chinese international students in New Zealand and from the narrative of students, we examined the relationship among educational difficulties, life satisfaction, and the use of SNSs. This study would help in further understanding how and why SNSs can be adopted in higher education to support effective overseas learning experiences. PMID- 22666101 TI - In vitro antibacterial and antifungal activity of salicylanilide benzoates. AB - The resistance to antimicrobial agents brings a need of novel antimicrobial agents. We have synthesized and found the in vitro antibacterial activity of salicylanilide esters with benzoic acid (2-(phenylcarbamoyl)phenyl benzoates) in micromolar range. They were evaluated in vitro for the activity against eight fungal and eight bacterial species. All derivatives showed a significant antibacterial activity against Gram-positive strains with minimum inhibitory concentrations >= 0.98 MUmol/L including methicillin-resistant Staphylococcus aureus strain. The most active compounds were 5-chloro-2-(3,4 dichlorophenylcarbamoyl)phenyl benzoate and 4-chloro-2-(4 (trifluoromethyl)phenylcarbamoyl)phenyl benzoate. The antifungal activity is significantly lower. PMID- 22666102 TI - Imaging review of skeletal tumors of the pelvis--part I: benign tumors of the pelvis. AB - The osseous pelvis is a well-recognized site of origin of numerous primary and secondary musculoskeletal tumors. The radiologic evaluation of a pelvic lesion often begins with the plain film and proceeds to computed tomography (CT), or magnetic resonance imaging (MRI) and possibly biopsy. Each of these modalities, with inherent advantages and disadvantages, has a role in the workup of pelvic osseous masses. Clinical history and imaging characteristics can significantly narrow the broad differential diagnosis for osseous pelvic lesions. The purpose of this review is to familiarize the radiologist with the presentation and appearance of some of the common benign neoplasms of the osseous pelvis and share our experience and approach in diagnosing these lesions. PMID- 22666103 TI - Impact of cypermethrin on fingerlings of common edible carp (Labeo rohita). AB - Laboratory evaluations were made to assess the toxicological and biochemical effect of cypermethrin on fingerlings of common edible freshwater culture carp (Labeo rohita). There was a significant negative (P < 0.05) correlation observed between effective doses of cypermethrin and exposure periods; that is, LC50 values decreased from 0.323 MUg/L (6 h) to > 0.278 MUg/L (12 h), > 0.240 MUg/L (18 h) and >0.205 MUg/L (24 h). Exposure to sublethal doses of cypermethrin for 24 h and 96 h exposure period caused significant (P < 0.05) time- and dose dependent alterations in total protein, total free amino acids, nucleic acids, glycogen, pyruvate, and lactate level and in the activity of enzyme protease, alanine aminotransferase, aspartate aminotransferase, acid phosphatases, alkaline phosphatases, acetylcholinesterase, and cytochrome oxidase in liver and muscle tissues of fish. Thus, cypermethrin has potent piscicidal activity against fingerlings of fish Labeo rohita and adversely affects their behavioural patterns, shifting aerobic pathway of fish respiration towards anaerobic pathway and also inhibiting energy production by suppressing ATP synthesis. PMID- 22666104 TI - The release of trace elements in the process of coal coking. AB - In order to assess the penetration of individual trace elements into the air through their release in the coal coking process, it is necessary to determine the loss of these elements by comparing their contents in the charge coal and in coke obtained. The present research covered four coke oven batteries differing in age, technology, and technical equipment. By using mercury analyzer MA-2 and the method of ICP MS As, Be, Cd, Co, Hg, Mn, Ni, Se, Sr, Tl, V, and Zn were determined in samples of charge coal and yielded coke. Basing on the analyses results, the release coefficients of selected elements were determined. Their values ranged from 0.5 to 94%. High volatility of cadmium, mercury, and thallium was confirmed. The tests have shown that although the results refer to the selected case studies, it may be concluded that the air purity is affected by controlled emission occurring when coke oven batteries are fired by crude coke oven gas. Fugitive emission of the trace elements investigated, occurring due to coke oven leaks and openings, is small and, is not a real threat to the environment except mercury. PMID- 22666106 TI - Outcome of induction of labour in nulliparous women following replacement of Cervidil with Prostin. AB - This study at the Logan Hospital, Australia, compared the outcome of induction of labour (IOL) in nulliparous women following replacement of Cervidil with Prostin. Eighty-two nulliparous women were identified for this retrospective cohort study over a period of three months on either side of the changed practice. Forty-four women received Prostin and 38 received Cervidil. Baseline characteristics were similar amongst the groups including maternal age, mean gestational age, and modified Bishop's score at the commencement of IOL. The incidence of amniotomy, oxytocin augmentation of labour, and rate of epidural use did not differ significantly between the groups. The mean time to delivery (vaginally or abdominally) showed a significant difference, with women receiving Prostin delivering earlier than those having Cervidil (P = 0.018). Women receiving Prostin were more likely to have assisted vaginal delivery compared to the Cervidil group (P = 0.04). PMID- 22666105 TI - Combined effect of subchondral drilling and hyaluronic acid with/without diacerein in full-thickness articular cartilage lesion in rabbits. AB - The osteochondral healing potential of hyaluronic acid (HA) plus diacerein was evaluated in subchondral-drilling- (SCD-) induced fibrocartilage generation in rabbits. A full-thickness chondral defect was created along the patellar groove of both knees and then SCD was subsequently performed only in the left knee. A week later, the rabbits were allocated into 3 groups to receive weekly intra articular (IA) injection for 5 weeks with normal saline solution (NSS) (group 1) or with HA (group 2 and group 3). Starting at the first IA injection, rabbits were also gavaged daily for 9 weeks with NSS (group 1 and group 2) or with diacerein (group 3). The animals were then sacrificed for evaluation. The newly formed tissue in SCD lesions showed significantly better histological grading scale and had higher content of type II collagen in HA-treated group compared to NSS control. In addition, adding oral diacerein to HA injection enhanced healing potential of HA. PMID- 22666107 TI - Usefulness of organic acid produced by Exiguobacterium sp. 12/1 on neutralization of alkaline wastewater. AB - The aim of this study was to investigate the role of organic acids produced by Exiguobacterium sp. strain 12/1 (DSM 21148) in neutralization of alkaline wastewater emanated from beverage industry. This bacterium is known to be able to grow in medium of pH as high as pH 12.0 and to neutralize alkaline industrial wastewater from pH 12.0 to pH 7.5. The initial investigation on the type of functional groups present in medium, carried out using FT-IR spectroscopy, revealed the presence of peaks corresponding to carbonyl group and hydroxyl group, suggesting the release of carboxylic acid or related metabolic product(s). The identification of specific carboxylic group, carried out using RP-HPLC, revealed the presence of a single peak in the culture supernatant with retention time most similar to formic acid. The concentration of acid produced on different carbon sources was studied as a function of time. Although acid was present in same final concentration, the rate of acid production was highest in case of medium supplemented with sucrose followed by fructose and glucose. The knowledge of metabolic products of the bacterium can be considered as a first step towards realization of its potential for large-scale bioremediation of alkaline wastewater from beverage industry. PMID- 22666108 TI - Secondary data analyses of subjective outcome evaluation data based on nine databases. AB - The purpose of this study was to evaluate the effectiveness of the Tier 1 Program of the Project P.A.T.H.S. (Positive Adolescent Training through Holistic Social Programmes) in Hong Kong by analyzing 1,327 school-based program reports submitted by program implementers. In each report, program implementers were invited to write down five conclusions based on an integration of the subjective outcome evaluation data collected from the program participants and program implementers. Secondary data analyses were carried out by aggregating nine databases, with 14,390 meaningful units extracted from 6,618 conclusions. Results showed that most of the conclusions were positive in nature. The findings generally showed that the workers perceived the program and program implementers to be positive, and they also pointed out that the program could promote holistic development of the program participants in societal, familial, interpersonal, and personal aspects. However, difficulties encountered during program implementation (2.15%) and recommendations for improvement were also reported (16.26%). In conjunction with the evaluation findings based on other strategies, the present study suggests that the Tier 1 Program of the Project P.A.T.H.S. is beneficial to the holistic development of the program participants. PMID- 22666109 TI - An efficient in vitro propagation protocol of cocoyam [Xanthosoma sagittifolium (L) Schott]. AB - Sprouted corm sections of "South Dade" white cocoyam were potted and maintained in a greenhouse for 8 weeks. Shoot tips of 3-5 mm comprising the apical meristem with 4-6 leaf primordial, and approximately 0.5 mm of corm tissue at the base. These explants were treated to be used into the culture medium. A modified Gamborg's B5 mineral salts supplemented with 0.05 MUM 1-naphthaleneacetic acid (NAA) were used throughout the study. Thidiazuron (TDZ) solution containing 0.01% dimethyl sulfoxide (DMSO) was used. Erlenmeyer flasks and test tubes were used for growing cultures. The effect of different media substrate, thidiazuron, and the interaction between TDZ and Benzylaminopurine (BAP) on cocoyam culture were tested. Results indicated that cocoyam can be successfully micropropagated in vitro through various procedures. All concentrations tested (5-20 MUM BAP and 1-4 MUM TDZ) produced more axillary shoots per shoot tip than the control without cytokinins. Greater proliferation rates were obtained through the use of 20 MUM BAP and 2 MUM TDZ, respectively, 12 weeks from initiation. Shoots produced with BAP were larger and more normal in appearance than those produced with TDZ, which were small, compressed, and stunted. The use of stationary liquid media is recommended for economic reasons. PMID- 22666110 TI - Setup and validation of flow cell systems for biofouling simulation in industrial settings. AB - A biofouling simulation system consisting of a flow cell and a recirculation tank was used. The fluid circulates at a flow rate of 350 L. h-1 in a semicircular flow cell with hydraulic diameter of 18.3 mm, corresponding to an average velocity of 0.275 m. s-1. Using computational fluid dynamics for flow simulation, an average wall shear stress of 0.4 Pa was predicted. The validity of the numerical simulations was visually confirmed by inorganic deposit formation (using kaolin particles) and also by direct observation of pathlines of tracer PVC particles using streak photography. Furthermore, the validity of chemostat assumptions was verified by residence time analysis. The system was used to assess the influence of the dilution rate on biofilm formation by Escherichia coli JM109(DE3). Two dilution rates of 0.013 and 0.0043 h-1 were tested and the results show that the planktonic cell concentration is increased at the lower dilution rate and that no significant changes were detected on the amount of biofilm formed in both conditions. PMID- 22666111 TI - Genetic diversity and population differentiation of the causal agent of citrus black spot in Brazil. AB - One of the most important diseases that affect sweet orange orchards in Brazil is the Citrus Black Spot that is caused by the fungus Guignardia citricarpa. This disease causes irreparable losses due to the premature falling of fruit, as well as its severe effects on the epidermis of ripe fruit that renders them unacceptable at the fresh fruit markets. Despite the fact that the fungus and the disease are well studied, little is known about the genetic diversity and the structure of the fungi populations in Brazilian orchards. The objective of this work was study the genetic diversity and population differentiation of G. citricarpa associated with four sweet orange varieties in two geographic locations using DNA sequence of ITS1-5.8S-ITS2 region from fungi isolates. We observed that different populations are closely related and present little genetic structure according to varieties and geographic places with the highest genetic diversity distributed among isolates of the same populations. The same haplotypes were sampled in different populations from the same and different orange varieties and from similar and different origins. If new and pathogenic fungi would become resistant to fungicides, the observed genetic structure could rapidly spread this new form from one population to others. PMID- 22666112 TI - Assessment of tools for marker-assisted selection in a marine commercial species: significant association between MSTN-1 gene polymorphism and growth traits. AB - Growth is a priority trait from the point of view of genetic improvement. Molecular markers linked to quantitative trait loci (QTL) have been regarded as useful for marker-assisted selection in complex traits as growth. Polymorphisms have been studied in five candidate genes influencing growth in gilthead seabream (Sparus aurata): the growth hormone (GH), insulin-like growth factor-1 (IGF-1), myostatin (MSTN-1), prolactin (PRL), and somatolactin (SL) genes. Specimens evaluated were from a commercial broodstock comprising 131 breeders (from which 36 males and 44 females contributed to the progeny). In all samples eleven gene fragments, covering more than 13,000 bp, generated by PCR-RFLP, were analyzed; tests were made for significant associations between these markers and growth traits. ANOVA results showed a significant association between MSTN-1 gene polymorphism and growth traits. Pairwise tests revealed several RFLPs in the MSTN 1 gene with significant heterogeneity of genotypes among size groups. PRL and MSTN-1 genes presented linkage disequilibrium. The MSTN-1 gene was mapped in the centromeric region of a medium-size acrocentric chromosome pair. PMID- 22666113 TI - Dual inoculation with mycorrhizal and saprotrophic fungi applicable in sustainable cultivation improves the yield and nutritive value of onion. AB - The aim of this paper was to test the use of dual microbial inoculation with mycorrhizal and saprotrophic fungi in onion cultivation to enhance yield while maintaining or improving the nutritional quality of onion bulbs. Treatments were two-factorial: (1) arbuscular mycorrhizal fungi (AMF): the mix corresponding to fungal part of commercial product Symbivit (Glomus etunicatum, G. microaggregatum, G. intraradices, G. claroideum, G. mosseae, and G. geosporum) (M1) or the single-fungus inoculum of G. intraradices BEG140 (M2) and (2) bark chips preinoculated with saprotrophic fungi (mix of Gymnopilus sp., Agrocybe praecox, and Marasmius androsaceus) (S). The growth response of onion was the highest for the M1 mix treatment, reaching nearly 100% increase in bulb fresh weight. The effectiveness of dual inoculation was proved by more than 50% increase. We observed a strong correlation (r = 0.83) between the growth response of onion bulbs and AM colonization. All inoculation treatments but the single fungus one enhanced significantly the total antioxidant capacity of bulb biomass, was the highest values being found for M1, S + M1, and S + M2. We observed some induced enhancement of the contents of mineral elements in bulb tissue (Mg and K contents for the M2 and M2, S, and S + M2 treatments, resp.). PMID- 22666114 TI - Morphofunctional traits and pollination mechanisms of Coronilla emerus L. flowers (Fabaceae). AB - It is accepted that the papilionaceous corolla of the Fabaceae evolved under the selective pressure of bee pollinators. Morphology and function of different parts of Coronilla emerus L. flowers were related to their role in the pollination mechanism. The corolla has a vexillum with red nectar lines, a keel hiding stamens and pistil, and two wing petals fasten to the keel with two notched folds. Pollinators land on the complex of keel and wings, trigger the protrusion of pollen and finally of the stigma from the keel tip. Data on pollen viability and stigma receptivity prove that flowers are proterandrous. The results of hand pollination experiments confirmed that insects are fundamental to set seed. Interaction with pollinators allows not only the transport of pollen but also the rupture of the stigmatic cuticle, necessary to achieve both allogamy and autogamy. Field observations showed that Hymenoptera, Lepidoptera, and Diptera visited the flowers. Only some of the Hymenoptera landed on the flowers from the front and elicited pollination mechanisms. Most of the insects sucked the nectar from the back without any pollen transfer. Finally, morphological and functional characteristics of C. emerus flowers are discussed in terms of floral larceny and reduction in pollination efficiency. PMID- 22666116 TI - Modelling the effects of ageing time of starch on the enzymatic activity of three amylolytic enzymes. AB - The effect of increasing ageing time (t) of starch on the activity of three amylolytic enzymes (Termamyl, San Super, and BAN) was investigated. Although all the enzymatic reactions follow michaelian kinetics, v(max) decreased significantly (P < 0.05) and K(M) increased (although not always significantly) with the increase in t. The conformational changes produced in the starch chains as a consequence of the ageing seemed to affect negatively the diffusivity of the starch to the active site of the enzymes and the release of the reaction products to the medium. A similar effect was observed when the enzymatic reactions were carried out with unaged starches supplemented with different concentrations of gelatine [G]. The inhibition in the amylolytic activities was best mathematically described by using three modified forms of the Michaelis-Menten model, which included a term to consider, respectively, the linear, exponential, and hyperbolic inhibitory effects of t and [G]. PMID- 22666117 TI - Electrochemical behavior of quinoxalin-2-one derivatives at mercury electrodes and its analytical use. AB - Derivatives of quinoxalin-2-one are interesting compounds with potential pharmacological activity. From this point of view, understanding of their electrochemical behavior is of great importance. In the present paper, a mechanism of electrochemical reduction of quinoxalin-2-one derivatives at mercury dropping electrode was proposed. Pyrazine ring was found to be the main electroactive center undergoing a pH-dependent two-electron reduction process. The molecule protonization of nitrogen in the position 4 precedes the electron acceptance forming a semiquinone radical intermediate which is relatively stable in acidic solutions. Its further reduction is manifested by separated current signal. A positive mesomeric effect of the nonprotonized amino group in the position 7 of the derivative III accelerates the semiquinone reduction yielding a single current wave. The suggested reaction mechanism was verified by means of direct current polarography, differential pulse, cyclic and elimination voltammetry, and coulometry with subsequent GC/MS analysis. The understanding of the mechanism was applied in developing of analytical method for the determination of the studied compounds. PMID- 22666115 TI - Salicylic acid attenuates gentamicin-induced nephrotoxicity in rats. AB - Gentamicin (GM) is a widely used antibiotic against serious and life-threatening infections, but its usefulness is limited by the development of nephrotoxicity. The present study was designed to determine the protective effect of salicylic acid (SA) in gentamicin-induced nephrotoxicity in rats. Quantitative evaluation of gentamicin-induced structural alterations and degree of functional alterations in the kidneys were performed by histopathological and biochemical analyses in order to determine potential beneficial effects of SA coadministration with gentamicin. Gentamicin was observed to cause a severe nephrotoxicity which was evidenced by an elevation of serum urea and creatinine levels. The significant increases in malondialdehyde (MDA) levels and protein carbonyl groups indicated that GM-induced tissue injury was mediated through oxidative reactions. On the other hand, simultaneous SA administration protected kidney tissue against the oxidative damage and the nephrotoxic effect caused by GM treatment. Exposure to GM caused necrosis of tubular epithelial cells. Necrosis of tubules was found to be prevented by SA pretreatment. The results from our study indicate that SA supplement attenuates oxidative-stress associated renal injury by reducing oxygen free radicals and lipid peroxidation in gentamicin-treated rats. PMID- 22666118 TI - Particulate matter and health risk under a changing climate: assessment for Portugal. AB - The potential impacts of climate-induced changes in air pollution levels and its impacts on population health were investigated. The IPCC scenario (SRES A2) was used to analyse the effects of climate on future PM10 concentrations over Portugal and their impact on short-term population exposure and mortality. The air quality modelling system has been applied with high spatial resolution looking on climate changes at regional scale. To quantify health impacts related to air pollution changes, the WHO methodology for health impact assessment was implemented. The results point to 8% increase of premature mortality attributed to future PM10 levels in Portugal. The pollution episodes with daily average PM10 concentration above the current legislated value (50 MUg.m-3) would be responsible for 81% of attributable cases. The absolute number of deaths attributable to PM10 under future climate emphasizes the importance of indirect effects of climate change on human health. PMID- 22666119 TI - Corrective bracing for severe idiopathic scoliosis in adolescence: influence of brace on trunk morphology. AB - Aim. The aim of the work was to study whether wearing a corrective brace by adolescent girls with severe idiopathic scoliosis can influence external shape of the trunk. Methods. Comparison of clinical deformity of two groups of girls matched for age and Cobb angle: group (1) of 23 girls, aged 14.9 +/- 1.3 years, Cobb angle 55.0 degrees +/- 6.8 degrees , who refused surgical treatment and have been wearing Cheneau brace for more than 6 months, compared with group (2) of 22 girls, aged 14.1 +/- 1.8 years, Cobb angle 59.7 degrees +/- 14.6 degrees never treated with corrective bracing. Clinical deformity was assessed with the Bunnell scoliometer (angle of trunk rotation ATR) and surface topography (posterior trunk symmetry index POTSI and Hump Sum HS). Results. The ATR in the primary curvature was 11.9 degrees +/- 3.4 degrees (5 degrees -18 degrees ) in group 1 versus 15.1 degrees +/- 5.6 degrees (6 degrees -25 degrees ) in group 2 (P = 0.027). The HS was 16.8 degrees +/- 3.8 versus 19.2 degrees +/- 4.6, respectively, P = 0.07. The POTSI value did not differ between groups. Conclusion. Girls with Cobb angle above 45 degrees, who have been subjected to brace treatment, revealed smaller clinical deformity of their back comparing to nontreated girls having similar radiological curvatures. PMID- 22666120 TI - The comet assay for the evaluation of genotoxic potential of landfill leachate. AB - Genotoxic assessment of landfill leachate before and after biological treatment was conducted with two human cell lines (Me45 and NHDF) and Daphnia magna somatic cells. The alkali version of comet assay was used to examine genotoxicity of leachate by DNA strand breaks analysis and its repair dynamics. The leachate samples were collected from Zabrze landfill, situated in the Upper Silesian Industrial District, Poland. Statistically significant differences (Kruskal Wallice ANOVA rank model) were observed between DNA strand breaks in cells incubated with leachate before and after treatment (P < 0.001). Nonparametric Friedman ANOVA confirmed time-reliable and concentration-reliable cells response to leachate concentration. Examinations of chemical properties showed a marked decrease in leachate parameters after treatment which correlate to reduced genotoxicity towards tested cells. Obtained results demonstrate that biological cotreatment of leachate together with municipal wastewater is an efficient method for its genotoxic potential reduction; however, treated leachate still possessed genotoxic character. PMID- 22666121 TI - Plants' metabolites as potential antiobesity agents. AB - Obesity and obesity-related complications are on the increase both in the developed and developing world. Since existing pharmaceuticals fail to come up with long-term solutions to address this issue, there is an ever-pressing need to find and develop new drugs and alternatives. Natural products, particularly medicinal plants, are believed to harbor potential antiobesity agents that can act through various mechanisms either by preventing weight gain or promoting weight loss amongst others. The inhibition of key lipid and carbohydrate hydrolyzing and metabolizing enzymes, disruption of adipogenesis, and modulation of its factors or appetite suppression are some of the plethora of targeted approaches to probe the antiobesity potential of medicinal plants. A new technology such as metabolomics, which deals with the study of the whole metabolome, has been identified to be a promising technique to probe the progression of diseases, elucidate their pathologies, and assess the effects of natural health products on certain pathological conditions. This has been applied to drug research, bone health, and to a limited extent to obesity research. This paper thus endeavors to give an overview of those plants, which have been reported to have antiobesity effects and highlight the potential and relevance of metabolomics in obesity research. PMID- 22666122 TI - Prevalence of avian pathogenic Escherichia coli (APEC) clone harboring sfa gene in Brazil. AB - Escherichia coli sfa+ strains isolated from poultry were serotyped and characterized by polymerase chain reaction (PCR) and amplified fragment length polymorphism (AFLP). Isolates collected from 12 Brazilian poultry farms mostly belonged to serogroup O6, followed by serogroups O2, O8, O21, O46, O78, O88, O106, O111, and O143. Virulence genes associated were: iuc 90%, fim 86% neuS 60%, hly 34%, tsh 28%, crl/csg 26%, iss 26%, pap 18%, and 14% cnf. Strains from the same farm presented more than one genotypic pattern belonging to different profiles in AFLP. AFLP showed a clonal relation between Escherichia coli sfa+ serogroup O6. The virulence genes found in these strains reveal some similarity with extraintestinal E. coli (ExPEC), thus alerting for potential zoonotic risk. PMID- 22666123 TI - Autophagic cell death is induced by acetone and ethyl acetate extracts from Eupatorium odoratum in vitro: effects on MCF-7 and vero cell lines. AB - Eupatorium odoratum (EO) contains many biologically active compounds, the anticancer effects of which are not well documented. This study evaluates the cytotoxic effects and mechanism of action of EO extracts on MCF-7 and Vero cell lines. Evaluation of the cytotoxic activity using MTT assay, morphological alterations, and apoptosis were carried out. Autophagy was evaluated by LC3-A protein expression. Cytotoxic activity, membrane blebbing and ballooning at 24 hours, replacement by mass vacuolation, and double membrane vesicles mimicking autophagy and cell death were observed in the cancer cells. No apoptosis was observed by DNA fragmentation assay. Overexpression of LC3-A protein indicated autophagic cell death. Cell cycle analysis showed G0 and G2/M arrest. The Vero cells did not show significant cell death at concentrations <100 MUg/mL. These results thus suggest that acetone and ethyl acetate extracts of EO induce cell death through induction of autophagy and hold potential for development as potential anticancer drugs. PMID- 22666124 TI - Antibiotic resistance of Salmonella enterica serovar Typhi in Kolkata, India, and in vitro experiments on effect of combined chemotherapy. AB - This communication states the changing patterns of Salmonella enterica serovar Typhi (S. Typhi) isolates causing enteric fever in and around Kolkata, India. Among the isolates resistance to ampicillin (A), chloramphenicol (C), cotrimoxazole (Co) and tetracycline (T) were plasmid mediated; the plasmid was unstable in S. Typhi, and the other enteric bacteria like Escherichia coli, Klebsiella pneumoniae and Proteus vulgaris were found to be the potential source of dissemination of such plasmids into S. Typhi. The infection with such S. Typhi strains were successfully treated with ciprofloxacin (Cp: MICs 0.0075-0.075 MUg mL-1) and/or ofloxacin (Ofx: MICs 0.0125-0.075 MUg mL-1), but in the later course, the S. Typhi strains, showing resistance to nalidixic acid, developed low level of resistance to Cp and Ofx, causing the treatment failure. Thus, the treatment regimen was shifted to the third generation cephalosporins like ceftriaxone (Ct) and cefotaxime (Cf). Keeping in mind the anticipation of development of resistance to Ct/Cf, we prepared the treatment regimen for MDR enteric fever, based on the double-drug synergy tests in vitro; Cp-gentamycin (FICI 0.121-0.216) and Cp-trimethoprim (FICI 0.14-0.483) combinations were found effective against S. Typhi isolates having decreased sensitivity to cp (MICs: 0.5 1.25 MUg mL-1). PMID- 22666125 TI - Physicochemical evaluation of the Upper Litani River watershed, Lebanon. AB - This study aims to determine the extent of groundwater damage in the Upper Litani River Basin (ULRB) after years of water mismanagement and overfertilization in what is considered to be Lebanon's largest fertile area. Physical and chemical samples were collected between 2005 and 2010 and analyzed using "The Standard Methods for the Examination of Water and Wastewater" (APHA, AWWA) in order to determine the extent of this pollution. The parameters included pH, ammonia, nitrate, nitrite, sulfate, phosphate, dissolved oxygen, and total dissolved solids. PMID- 22666126 TI - A study on methane and nitrous oxide emissions characteristics from anthracite circulating fluidized bed power plant in Korea. AB - In order to tackle climate change effectively, the greenhouse gas emissions produced in Korea should be assessed precisely. To do so, the nation needs to accumulate country-specific data reflecting the specific circumstances surrounding Korea's emissions. This paper analyzed element contents of domestic anthracite, calorific value, and concentration of methane (CH4) and nitrous oxide (N2O) in the exhaust gases from circulating fluidized bed plant. The findings showed the concentration of CH4 and N2O in the flue gas to be 1.85 and 3.25 ppm, respectively, and emission factors were 0.486 and 2.198 kg/TJ, respectively. The CH4 emission factor in this paper was 52% lower than default emission factor presented by the IPCC. The N2O emission factor was estimated to be 46% higher than default emission factor presented by the IPCC. This discrepancy can be attributable to the different methods and conditions of combustion because the default emission factors suggested by IPCC take only fuel characteristics into consideration without combustion technologies. Therefore, Korea needs to facilitate research on a legion of fuel and energy consumption facilities to develop country-specific emission factors so that the nation can have a competitive edge in the international climate change convention in the years to come. PMID- 22666127 TI - Occurrence of morphological and anatomical adaptive traits in young and adult plants of the rare Mediterranean cliff species Primula palinuri Petagna. AB - Cliffs worldwide are known to be reservoirs of relict biodiversity. Despite the presence of harsh abiotic conditions, large endemic floras live in such environments. Primula palinuri Petagna is a rare endemic plant species, surviving on cliff sites along a few kilometres of the Tyrrhenian coast in southern Italy. This species is declared at risk of extinction due to human impact on the coastal areas in question. Population surveys have shown that most of the plants are old individuals, while seedlings and plants at early stages of development are rare. We followed the growth of P. palinuri plants from seed germination to the adult phase and analysed the morphoanatomical traits of plants at all stages of development. Our results showed that the pressure of cliff environmental factors has been selected for seasonal habitus and structural adaptive traits in this species. The main morphoanatomical modifications are suberized cell layers and accumulation of phenolic compounds in cell structures. These features are strictly related to regulation of water uptake and storage as well as defence from predation. However, we found them well established only in adult plants and not in juvenile individuals. These findings contribute to explain the rare recruitment of the present relict populations, identifying some of the biological traits which result in species vulnerability. PMID- 22666128 TI - Aflatoxigenic fungi and aflatoxins in Portuguese almonds. AB - Aflatoxin contamination of nuts is an increasing concern to the consumer's health. Portugal is a big producer of almonds, but there is no scientific knowledge on the safety of those nuts, in terms of mycotoxins. The aim of this paper was to study the incidence of aflatoxigenic fungi and aflatoxin contamination of 21 samples of Portuguese almonds, and its evolution throughout the various stages of production. All fungi belonging to Aspergillus section Flavi were identified and tested for their aflatoxigenic ability. Almond samples were tested for aflatoxin contamination by HPLC-fluorescence. In total, 352 fungi belonging to Aspergillus section Flavi were isolated from Portuguese almonds: 127 were identified as A. flavus (of which 28% produced aflatoxins B), 196 as typical or atypical A. parasiticus (all producing aflatoxins B and G), and 29 as A. tamarii (all nonaflatoxigenic). Aflatoxins were detected in only one sample at 4.97 MUg/kg. PMID- 22666129 TI - Mechanical, rheological, and bioactivity properties of ultra high-molecular weight polyethylene bioactive composites containing polyethylene glycol and hydroxyapatite. AB - Ultrahigh-molecular-weight polyethylene/high-density polyethylene (UHMWPE/HDPE) blends prepared using polyethylene glycol PEG as the processing aid and hydroxyapatite (HA) as the reinforcing filler were found to be highly processable using conventional melt blending technique. It was demonstrated that PEG reduced the melt viscosity of UHMWPE/HDPE blend significantly, thus improving the extrudability. The mechanical and bioactive properties were improved with incorporation of HA. Inclusion of HA from 10 to 50 phr resulted in a progressive increase in flexural strength and modulus of the composites. The strength increment is due to the improvement on surface contact between the irregular shape of HA and polymer matrix by formation of mechanical interlock. The HA particles were homogenously distributed even at higher percentage showed improvement in wetting ability between the polymer matrix and HA. The inclusion of HA enhanced the bioactivity properties of the composite by the formation of calcium phosphate (Ca-P) precipitates on the composite surface as proven from SEM and XRD analysis. PMID- 22666130 TI - An investigation of the basic physics of irrigation in urology and the role of automated pump irrigation in cystoscopy. AB - OBJECTIVE: To investigate the effects of height, external pressure, and bladder fullness on the flow rate in continuous, non-continuous cystoscopy and the automated irrigation fluid pumping system (AIFPS). MATERIALS: Each experiment had two 2-litre 0.9% saline bags connected to a continuous, non-continuous cystoscope or AIFPS via irrigation tubing. Other equipment included height-adjustable drip poles, uroflowmetry devices, and model bladders. METHODS: In Experiment 1, saline bags were elevated to measure the increment in flow rate. In Experiment 2, saline bags were placed under external pressures to evaluate the effect on flow rate. In Experiment 3, flow rate changes in response to variable bladder fullness were measured. RESULTS: Elevating saline bags caused an increase in flow rates, however the increment slowed down beyond a height of 80 cm. Increase in external pressure on saline bags elevated flow rates, but inconsistently. A fuller bladder led to a decrease in flow rates. In all experiments, the AIFPS posted consistent flow rates. CONCLUSIONS: Traditional irrigation systems were susceptible to changes in height of irrigation solution, external pressure application, and bladder fullness thus creating inconsistent flow rates. The AIFPS produced consistent flow rates and was not affected by any of the factors investigated in the study. PMID- 22666131 TI - Some problems in proving the existence of the universal common ancestor of life on Earth. AB - Although overwhelming circumstantial evidence supports the existence of the universal common ancestor of all extant life on Earth, it is still an open question whether the universal common ancestor existed or not. Theobald (Nature 465, 219-222 (2010)) recently challenged this problem with a formal statistical test applied to aligned sequences of conservative proteins sampled from all domains of life and concluded that the universal common ancestor hypothesis holds. However, we point out that there is a fundamental flaw in Theobald's method which used aligned sequences. We show that the alignment gives a strong bias for the common ancestor hypothesis, and we provide an example that Theobald's method supports a common ancestor hypothesis for two apparently unrelated families of protein-encoding sequences (cytb and nd2 of mitochondria). This arouses suspicion about the effectiveness of the "formal" test. PMID- 22666133 TI - Computed tomography to estimate the representative elementary area for soil porosity measurements. AB - Computed tomography (CT) is a technique that provides images of different solid and porous materials. CT could be an ideal tool to study representative sizes of soil samples because of the noninvasive characteristic of this technique. The scrutiny of such representative elementary sizes (RESs) has been the target of attention of many researchers related to soil physics field owing to the strong relationship between physical properties and size of the soil sample. In the current work, data from gamma-ray CT were used to assess RES in measurements of soil porosity (phi). For statistical analysis, a study on the full width at a half maximum (FWHM) of the adjustment of distribution of phi at different areas (1.2 to 1162.8 mm2) selected inside of tomographic images was proposed herein. The results obtained point out that samples with a section area corresponding to at least 882.1 mm2 were the ones that provided representative values of phi for the studied Brazilian tropical soil. PMID- 22666132 TI - Immunocompetent mice model for dengue virus infection [corrected]. AB - Dengue fever is a noncontagious infectious disease caused by dengue virus (DENV). DENV belongs to the family Flaviviridae, genus Flavivirus, and is classified into four antigenically distinct serotypes: DENV-1, DENV-2, DENV-3, and DENV-4. The number of nations and people affected has increased steadily and today is considered the most widely spread arbovirus (arthropod-borne viral disease) in the world. The absence of an appropriate animal model for studying the disease has hindered the understanding of dengue pathogenesis. In our study, we have found that immunocompetent C57BL/6 mice infected intraperitoneally with DENV-1 presented some signs of dengue disease such as thrombocytopenia, spleen hemorrhage, liver damage, and increase in production of IFNgamma and TNFalpha cytokines. Moreover, the animals became viremic and the virus was detected in several organs by real-time RT-PCR. Thus, this animal model could be used to study mechanism of dengue virus infection, to test antiviral drugs, as well as to evaluate candidate vaccines. PMID- 22666134 TI - Qualitative evaluation of project P.A.T.H.S.: an integration of findings based on program participants. AB - An integration of the qualitative evaluation findings collected in different cohorts of students who participated in Project P.A.T.H.S. (Positive Adolescent Training through Holistic Social Programmes) (n = 252 students in 29 focus groups) was carried out. With specific focus on how the informants described the program, results showed that the descriptions were mainly positive in nature, suggesting that the program was well received by the program participants. When the informants were invited to name three metaphors that could stand for the program, positive metaphors were commonly used. Beneficial effects of the program in different psychosocial domains were also voiced by the program participants. The qualitative findings integrated in this paper provide further support for the effectiveness of the Tier 1 Program of Project P.A.T.H.S. in promoting holistic development in Chinese adolescents in Hong Kong. PMID- 22666135 TI - PHBV/PCL microparticles for controlled release of resveratrol: physicochemical characterization, antioxidant potential, and effect on hemolysis of human erythrocytes. AB - Microparticles of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and poly(epsilon-caprolactone) (PCL) containing resveratrol were successfully prepared by simple emulsion/solvent evaporation. All formulations showed suitable encapsulation efficiency values higher than 80%. PHBV microparticles revealed spherical shape with rough surface and presence of pores. PCL microparticles were spherically shaped with smooth surface. Fourier-transformed infrared spectra demonstrated no chemical bond between resveratrol and polymers. X-ray powder diffraction patterns and differential scanning calorimetry analyses indicated that microencapsulation led to drug amorphization. These PHBV/PCL microparticles delayed the dissolution profile of resveratrol. Release profiles were better fitted to biexponential equation. The hypochlorous-acid-scavenging activity and 2,2-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation discoloration assay confirmed that the antioxidant activity of PHBV/PCL microparticles was kept, but was dependent on the microparticle morphology and dissolution profile. Resveratrol-loaded PHBV/PCL microparticles showed no cytotoxic effect on red blood cells. PMID- 22666136 TI - Inactivation of the catalytic subunit of cAMP-dependent protein kinase A causes delayed appressorium formation and reduced pathogenicity of Colletotrichum gloeosporioides. AB - The cyclic AMP- (cAMP-) dependent protein kinase A signaling pathway is one of the major signaling pathways responsible for regulation of the morphogenesis and pathogenesis of several pathogenic fungi. To evaluate the role of this pathway in the plant pathogenic fungus, Colletotrichum gloeosporioides, the gene encoding the catalytic subunit of cAMP-dependent protein kinase A, CgPKAC, was cloned, inactivated, and the mutant was analyzed. Analysis of the Cgpkac mutant generated via gene replacement showed that the mutants were able to form appressoria; however, their formation was delayed compared to the wild type. In addition, the mutant conidia underwent bipolar germination after appressoria formation, but no appressoria were generated from the second germ tube. The mutants also showed reduced ability to adhere to a hydrophobic surface and to degrade lipids localized in the appressoria. Based on the number of lesions produced during a pathogenicity test, the mutant's ability to cause disease in healthy mango fruits was reduced, which may be due to failure to penetrate into the fruit. These findings indicate that cAMP-dependent protein kinase A has an important role in regulating morphogenesis and is required for pathogenicity of C. gloeosporioides. PMID- 22666137 TI - Effects of feeding of two potentially probiotic preparations from lactic acid bacteria on the performance and faecal microflora of broiler chickens. AB - The aim of this study was to evaluate the potential of two probiotic preparations, containing live lactic acid bacteria (Lactococcus lactis CECT 539 and Lactobacillus casei CECT 4043) and their products of fermentation (organic acids and bacteriocins), as a replacement for antibiotics in stimulating health and growth of broiler chickens. The effects of the supplementation of both preparations (with proven probiotic effect in weaned piglets) and an antibiotic (avilamycin) on body weight gain (BWG), feed intake (FI), feed consumption efficiency (FCE), relative intestinal weight, and intestinal microbiota counts were studied in 1-day posthatch chickens. The experiments were conducted with medium-growth Sasso X44 chickens housed in cages and with nutritional stressed Ross 308 broiler distributed in pens. Consumption of the different diets did not affect significantly the final coliform counts in Sasso X44 chickens. However, counts of lactic acid bacteria and mesophilic microorganisms were higher in the animals receiving the two probiotic preparations (P < 0.05). In the second experiment, although no differences in BWG were observed between treatments, Ross 308 broilers receiving the probiotic Lactobacillus preparation exhibited the lowest FCE values and were considered the most efficient at converting feed into live weight. PMID- 22666138 TI - Investigating violence and control dyadically in a help-seeking sample from Mozambique. AB - A sample of 1442 women attending a Forensic Healthcare Service provided information on their own and their partners' use of controlling behaviors, partner violence, and sexual abuse, as well as their own experiences of childhood abuse. Using Johnson's typology, the relationships were categorized as Nonviolent, Intimate Terrorism, or Situational Couple Violence. Findings suggest that help-seeking women's experiences of intimate violence may be diverse, with their roles ranging from victim to perpetrator. PMID- 22666139 TI - Qualitative evaluation of the project P.A.T.H.S.: an integration of findings based on program implementers. AB - An integration of the qualitative evaluation findings collected from program implementers conducting the Project P.A.T.H.S. (Positive Adolescent Training through Holistic Social Programmes) in different years (n = 177 participants in 36 focus groups) was carried out. General qualitative data analyses utilizing intra and interrater reliability techniques were performed. Results showed that the descriptors used to describe the program and the metaphors named by the informants that could stand for the program were generally positive in nature. Program participants also perceived the program to be beneficial to the development of the students in different psychosocial domains. The present study further supports the effectiveness of the Tier 1 Program of the Project P.A.T.H.S. in Hong Kong based on the perspective of the program implementers. PMID- 22666140 TI - Benchmarking strategies for measuring the quality of healthcare: problems and prospects. AB - Over the last few years, increasing attention has been directed toward the problems inherent to measuring the quality of healthcare and implementing benchmarking strategies. Besides offering accreditation and certification processes, recent approaches measure the performance of healthcare institutions in order to evaluate their effectiveness, defined as the capacity to provide treatment that modifies and improves the patient's state of health. This paper, dealing with hospital effectiveness, focuses on research methods for effectiveness analyses within a strategy comparing different healthcare institutions. The paper, after having introduced readers to the principle debates on benchmarking strategies, which depend on the perspective and type of indicators used, focuses on the methodological problems related to performing consistent benchmarking analyses. Particularly, statistical methods suitable for controlling case-mix, analyzing aggregate data, rare events, and continuous outcomes measured with error are examined. Specific challenges of benchmarking strategies, such as the risk of risk adjustment (case-mix fallacy, underreporting, risk of comparing noncomparable hospitals), selection bias, and possible strategies for the development of consistent benchmarking analyses, are discussed. Finally, to demonstrate the feasibility of the illustrated benchmarking strategies, an application focused on determining regional benchmarks for patient satisfaction (using 2009 Lombardy Region Patient Satisfaction Questionnaire) is proposed. PMID- 22666141 TI - CD4+CD25highCD127low regulatory T cells in peripheral blood are not an independent factor for chronic graft-versus-host disease after allogeneic stem cell transplantation. AB - BACKGROUND: The therapeutic efficacy of allogeneic hemopoietic stem cell transplantation (HSCT) largely relies on the graft-versus-leukemia (GVL) effect. Uncontrolled graft-versus-host disease (GVHD) is a feared complication of HSCT. Regulatory T cells (Treg) are a subset of CD4+ T-helper cells believed to maintain tolerance after HSCT. It remains unclear whether low peripheral blood Treg have an impact on the risk for acute (aGVHD) and chronic GVHD (cGVHD). METHODS: In this paper we enumerated the CD4+CD25highCD127low Treg in the peripheral blood of 84 patients after at least 150 days from HSCT and in 20 healthy age-matched controls. RESULTS: Although similar mean lymphocyte counts were found in patients and controls, CD3+CD4+ T-cell counts were significantly lower in patients. Patients also had significantly lower Treg percentages among lymphocytes as compared to controls. Patients with cGVHD had even higher percentages of Treg if compared to patients without cGVHD. In multivariate analysis, Treg percentages were not an independent factor for cGVHD. CONCLUSIONS: This paper did not show a relation between deficient peripheral blood Treg and cGVHD, therefore cGVHD does not seem to occur as a result of peripheral Treg paucity. PMID- 22666142 TI - Screening for depression, sleep-related disturbances, and anxiety in patients with adenocarcinoma of the pancreas: a preliminary study. AB - PURPOSE: Screening for depression, sleep-related disturbances, and anxiety in patients with diagnosed adenocarcinoma of the pancreas. MATERIALS AND METHODS: Patients were evaluated at initial consultation and subsequent visits at the multidisciplinary pancreatic cancer clinic at our University Cancer Center. Cross sectional and longitudinal psychosocial distress was assessed utilizing Personal Health Questionnaire 9 (PHQ9) to screen for depression and monitor symptoms, the Penn State Worry Questionnaire (PSWQ) for generalized anxiety, and the University of Michigan Sleep Questionnaire to monitor sleep symptoms. RESULTS: Twenty-two patients diagnosed with pancreatic cancer participated during the 6-month pilot study with longitudinal followup for thirteen patients. In this study, mild-to moderate depressive symptoms, anxiety, and potential sleep problems were common. The main finding of the study was 23% of the patients who were part of this pilot project screened positive for moderately severe major depressive symptoms, likely anxiety disorder or a potential sleep disorder during the study. One patient screened positive for moderately severe depressive symptoms in longitudinal followup. CONCLUSIONS: Depression, anxiety, and sleep problems are evident in patients with pancreatic cancer. Prospective, longitudinal studies, with larger groups of patients, are needed to determine if these comorbid symptoms impact outcome and clinical course. PMID- 22666143 TI - Therapeutic angiogenesis using basic fibroblast growth factor in combination with a collagen matrix in chronic hindlimb ischemia. AB - Although therapeutic angiogenesis by angiogenic cytokines is a feasible strategy to improve regional blood flow in ischemic regions, the optimal delivery mode needs to be established. Here we designed a complex of collagen matrix (CM) and basic fibroblast growth factor (bFGF) and evaluated its proangiogenic effect in ischemic hindlimbs. The bFGF-CM was prepared using lyophilization. The morphology, porosity and toxicity of CM were examined. The bFGF releasing profile and bioactivity of released bFGF were assessed. bFGF-CM was intramuscularly implanted into the rabbit ischemic hindlimb model. Oxygen saturation parameters (OSP) of ischemic hindlimbs was measured to evaluate the extremity perfusion at intervals. Histological examination was performed to evaluate the level of angiogenesis. The CM and bFGF-CM were of identical multiporous structure lacking cytotoxicity. The releasing profile lasted 10 days and the released bFGF remained bioactive. OSP in bFGF-CM group was significantly higher than that in CM, bFGF and ischemic groups at 2 and 4 weeks. The number of capillaries and mature vessels in bFGF-CM group were significantly greater than that in untreated control, CM and bFGF groups. Therefore, bFGF-CM enables the safe and effective long-term release of bFGF with improved angiogenesis in ischemic hindlimbs compared with CM devoid of bFGF. PMID- 22666144 TI - The project P.A.T.H.S. in Hong Kong--lessons learned and implications for positive youth development programs. AB - The Project P.A.T.H.S. is a positive youth development program which attempts to promote holistic development of junior secondary schools in Hong Kong. It is ground breaking in terms of the number of schools participating in the project and financial resources injected into the project. Based on the experiences gained from the implementation of the project and evaluation data collected from 2005 to 2011, several issues pertinent to the development of positive youth development programs in the Chinese culture are discussed. These issues include complexity of program development, importance of training, identification of factors governing program implementation, need for evaluation, and promotion of sustainability of the program in the long run. PMID- 22666145 TI - Insecticidal activity of Bacillus thuringiensis strains isolated from soil and water. AB - We attempted to search novel Bacillus thuringiensis strains that produce crystals with potential utility in plant protection and with higher activity than strains already used in biopesticide production. Seven B. thuringiensis soil and water isolates were used in the research. We predicted the toxicity of their crystals by cry gene identification employing PCR method. The isolate MPU B63 with interesting, according to us, genes content was used in evaluating its crystal toxicity against Cydia pomonella caterpillars. The strain MPU B63 was cultured from water sample and had cry1Ab, cry1B, and cry15 genes. The LC50 crystals of MPU B63 were compared to LC50 of commercial bioinsecticide Foray determined against C. pomonella (codling moth). The activity of MPU B63 inclusions against codling moth larvae was approximately 24-fold higher than that of Foray. The results are a promising introduction for further study evaluating the potential usefulness of isolate MPU B63 crystals in plant protection. PMID- 22666146 TI - Relation of secondhand smoking to mild cognitive impairment in older inpatients. AB - Up to now, controversy still exists regarding the role of secondhand smoking (SHS) in developing cognitive impairment. This study aimed to evaluate the prevalence of SHS in hospitalized older patients with cognitive deficit, particularly in those with mild cognitive impairment (MCI). Smoking history was classified into four groups: never smokers, former-active smokers/no SHS, active smokers, and secondhand smokers, and cognitive function into three levels: normal cognition (C), MCI, and dementia. A total of 933 older subjects with diagnoses of MCI (n = 98), dementia (n = 124), or C (n = 711) were enrolled in this cross sectional study. As expected, patients with dementia had significantly higher frequency of former-active smokers than cognitively normal. Moreover, patients with MCI showed a significantly higher frequency of active and secondhand smokers than patients with dementia or C. A smoking history is very frequent in older patients with dementia. Patients with MCI had even higher rate of exposure to active or secondhand smoking. PMID- 22666148 TI - Kinetic analysis for macrocyclizations involving anionic template at the transition state. AB - Several kinetic models for the macrocyclization of a C2 pseudopeptide with a dihalide through a S(N)2 reaction have been developed. These models not only focus on the kinetic analysis of the main macrocyclization reaction, but also consider the competitive oligomerization/polymerization processes yielding undesired oligomeric/polymeric byproducts. The effect of anions has also been included in the kinetic models, as they can act as catalytic templates in the transition state reducing and stabilizing the transition state. The corresponding differential equation systems for each kinetic model can be solved numerically. Through a comprehensive analysis of these results, it is possible to obtain a better understanding of the different parameters that are involved in the macrocyclization reaction mechanism and to develop strategies for the optimization of the desired processes. PMID- 22666147 TI - Process evaluation of a positive youth development program in Hong Kong based on different cohorts. AB - There are only a few process evaluation studies on positive youth development programs, particularly in the Chinese context. This study aims to examine the quality of implementation of a positive youth development program (the Project P.A.T.H.S.: Positive Adolescent Training through Holistic Social Programmes) and investigate the relationships among program adherence, process factors, implementation quality, and perceived program success. Process evaluation of 97 classroom-based teaching units was conducted in 62 schools from 2005 to 2009. Findings based on different cohorts generally showed that there were high overall program adherence and implementation quality. Program adherence and implementation process were highly correlated with quality and success of the program. Multiple regression analyses further showed that both implementation process and program adherence are significant predictors of program quality and success. Theoretical and practical implications of the findings are discussed. PMID- 22666149 TI - Personal construction of cough medicine among young substance abusers in Hong Kong. AB - Although cough medicine abuse is a growing problem in many places, there is no study examining the views of young substance abusers toward cough medicine. The objective of this study was to examine personal constructions of cough medicine abusers via the repertory grid tests (N = 11). Several observations are highlighted from the study. First, personal constructions of cough medicine were mixed, including the benefits and harmful effects of its abuse. Second, although the informants perceived cough medicine to be addictive and harmful, they perceived cough medicine to be less addictive and less harmful than did heroin. Third, while the informants construed cough medicine to be similar to ketamine and marijuana, they also perceived cough medicine to possess some characteristics of heroin. Fourth, relative to the construed similarity between heroin and the gateway drugs (cigarette, beer, and liquor), the informants construed cough medicine to be more similar to the gateway drugs. Finally, a higher level of perceived dissimilarity between cough medicine and gateway drugs was related to a higher level of perceived harm of cough medicine abuse. PMID- 22666150 TI - The solid phase extraction of some metal ions using palladium nanoparticles attached to silica gel chemically bonded by silica-bonded N-propylmorpholine as new sorbent prior to their determination by flame atomic absorption spectroscopy. AB - In this research at first palladium nanoparticle attached to a new chemically bonded silica gel has been synthesized and has been characterized with different techniques such as X-ray diffraction (XRD), fourier transform infrared (FT-IR), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). Then, this new sorbent (chemically modified silica gel with N-propylmorpholine (PNP-SBNPM)) was efficiently used for preconcentration of some metal ions in various food samples. The influence of effective variables including mass of sorbent, flow rate, pH of sample solutions and condition of eluent such as volume, type and concentration on the recoveries of understudy metal ions were investigated. Following the optimization of variables, the interfering effects of some foreign ions on the preconcentration and determination of the investigated metal ions described. At optimum values of variables, all investigated metal ions were efficiently recovered with efficiency more than 95%, relative standard deviation (RSD) between 2.4 and 2.8, and detection limit in the range of 1.4-2.7 ng mL-1. The present method is simple and rapidly applicable for the determination of the understudied metal ions (ng mL-1) in different natural food samples. PMID- 22666152 TI - Aerobic fitness evaluation during walking tests identifies the maximal lactate steady state. AB - OBJECTIVE: The aim of this study was to verify the possibility of lactate minimum (LM) determination during a walking test and the validity of such LM protocol on predicting the maximal lactate steady-state (MLSS) intensity. DESIGN: Eleven healthy subjects (24.2 +/- 4.5 yr; 74.3 +/- 7.7 kg; 176.9 +/- 4.1 cm) performed LM tests on a treadmill, consisting of walking at 5.5 km . h-1 and with 20-22% of inclination until voluntary exhaustion to induce metabolic acidosis. After 7 minutes of recovery the participants performed an incremental test starting at 7% incline with increments of 2% at each 3 minutes until exhaustion. A polynomial modeling approach (LMp) and a visual inspection (LMv) were used to identify the LM as the exercise intensity associated to the lowest [bLac] during the test. Participants also underwent to 2-4 constant intensity tests of 30 minutes to determine the MLSS intensity. RESULTS: There were no differences among LMv (12.6 +/- 1.7%), LMp (13.1 +/- 1.5%), and MLSS (13.6 +/- 2.1%) and the Bland and Altman plots evidenced acceptable agreement between them. CONCLUSION: It was possible to identify the LM during walking tests with intensity imposed by treadmill inclination, and it seemed to be valid on identifying the exercise intensity associated to the MLSS. PMID- 22666153 TI - Higher P-wave dispersion in migraine patients with higher number of attacks. AB - OBJECTIVE AND AIM: An imbalance of the sympathetic system may explain many of the clinical manifestations of the migraine. We aimed to evaluate P-waves as a reveal of sympathetic system function in migraine patients and healthy controls. MATERIALS AND METHODS: Thirty-five episodic type of migraine patients (complained of migraine during 5 years or more, BMI < 30 kg/m2) and 30 controls were included in our study. We measured P-wave durations (minimum, maximum, and dispersion) from 12-lead ECG recording during pain-free periods. ECGs were transferred to a personal computer via a scanner and then used for magnification of x400 by Adobe Photoshop software. RESULTS: P-wave durations were found to be similar between migraine patients and controls. Although P WD (P-wave dispersion) was similar, the mean value was higher in migraine subjects. P WD was positively correlated with P max (P < 0.01). Attacks number per month and male gender were the factors related to the P WD (P < 0.01). CONCLUSIONS: Many previous studies suggested that increased sympathetic activity may cause an increase in P WD. We found that P WD of migraine patients was higher than controls, and P WD was related to attacks number per month and male gender. Further studies are needed to explain the chronic effects of migraine. PMID- 22666151 TI - Identification of proteins with potential osteogenic activity present in the water-soluble matrix proteins from Crassostrea gigas nacre using a proteomic approach. AB - Nacre, when implanted in vivo in bones of dogs, sheep, mice, and humans, induces a biological response that includes integration and osteogenic activity on the host tissue that seems to be activated by a set of proteins present in the nacre water-soluble matrix (WSM). We describe here an experimental approach that can accurately identify the proteins present in the WSM of shell mollusk nacre. Four proteins (three gigasin-2 isoforms and a cystatin A2) were for the first time identified in WSM of Crassostrea gigas nacre using 2DE and LC-MS/MS for protein identification. These proteins are thought to be involved in bone remodeling processes and could be responsible for the biocompatibility shown between bone and nacre grafts. These results represent a contribution to the study of shell biomineralization process and opens new perspectives for the development of new nacre biomaterials for orthopedic applications. PMID- 22666154 TI - Growth and anatomical parameters of adventitious roots formed on mung bean hypocotyls are correlated with galactoglucomannan oligosaccharides structure. AB - The effect of galactoglucomannan oligosaccharides (GGMOs) compared with chemically modified oligosaccharides, GGMOs-g (with reduced number of D-galactose side chains) and GGMOs-r (with reduced reducing ends) on mung bean (Vigna radiata (L.) Wilczek) adventitious roots formation, elongation, and anatomical structure have been studied. All types of oligosaccharides influenced adventitious root formation in the same way: stimulation in the absence of exogenous auxin and inhibition in the presence of exogenous auxin. Both reactions are probably related with the presence/content of endogenous auxin in plant cuttings. However, the adventitious root length was inhibited by GGMOs both in the absence as well as in the presence of auxin (IBA or NAA), while GGMOs-g inhibition was significantly weaker compared with GGMOs. GGMOs-r were without significant difference on both processes, compared with GGMOs. GGMOs affected not only the adventitious root length but also their anatomy in dependence on the combination with certain type of auxin. The oligosaccharides influenced cortical cells division, which was reflected in the cortex area and in the root diameter. All processes followed were dependent on oligosaccharides chemical structure. The results suggest also that GGM-derived oligosaccharides may play an important role in adventitious roots elongation but not in their formation. PMID- 22666155 TI - Recognition for positive behavior as a critical youth development construct: conceptual bases and implications on youth service development. AB - Recognition for positive behavior is an appropriate response of the social environment to elicit desirable external behavior among the youth. Such positive responses, rendered from various social systems, include tangible and intangible reinforcements. The following theories are used to explain the importance of recognizing positive behavior: operational conditioning, observational learning, self-determination, and humanistic perspective. In the current work, culturally and socially desirable behaviors are discussed in detail with reference to Chinese adolescents. Positive behavior recognition is especially important to adolescent development because it promotes identity formation as well as cultivates moral reasoning and social perspective thinking from various social systems. The significance of recognizing positive behavior is illustrated through the support, tutorage, invitation, and subsidy provided by Hong Kong's social systems in recognition of adolescent volunteerism. The practical implications of positive behavior recognition on youth development programs are also discussed in this work. PMID- 22666156 TI - Comparative study of various E. coli strains for biohydrogen production applying response surface methodology. AB - The proper strategy to establish efficient hydrogen-producing biosystems is the biochemical, physiological characterization of hydrogen-producing microbes followed by metabolic engineering in order to give extraordinary properties to the strains and, finally, bioprocess optimization to realize enhanced hydrogen fermentation capability. In present paper, it was aimed to show the utility both of strain engineering and process optimization through a comparative study of wild-type and genetically modified E. coli strains, where the effect of two major operational factors (substrate concentration and pH) on bioH2 production was investigated by experimental design and response surface methodology (RSM) was used to determine the suitable conditions in order to obtain maximum yields. The results revealed that by employing the genetically engineered E. coli (DJT 135) strain under optimized conditions (pH: 6.5; Formate conc.: 1.25 g/L), 0.63 mol H2/mol formate could be attained, which was 1.5 times higher compared to the wild type E. coli (XL1-BLUE) that produced 0.42 mol H2/mol formate (pH: 6.4; Formate conc.: 1.3 g/L). PMID- 22666157 TI - Prosocial norms as a positive youth development construct: a conceptual review. AB - Prosocial norms like reciprocity, social responsibility, altruism, and volunteerism are ethical standards and beliefs that youth development programs often want to promote. This paper reviews evolutionary, social-cognitive, and developmental theories of prosocial development and analyzes how young people learn and adopt prosocial norms. The paper showed that very few current theories explicitly address the issue of how prosocial norms, in form of feelings of moral obligations, may be challenged by a norm of self-interest and social circumstances when prosocial acts are needed. It is necessary to develop theories which put prosocial norms as a central construct, and a new social cognitive theory of norm activation has the potential to help us understand how prosocial norms may be applied. This paper also highlights how little we know about young people perceiving and receiving prosocial norms and how influential of school policies and peer influence on the prosocial development. Lastly, while training of interpersonal competence (e.g., empathy, moral reasoning, etc.) was commonly used in the youth development, their effectiveness was not systematically evaluated. It will also be interesting to examine how computer and information technology or video games may be used in e-learning of prosocial norms. PMID- 22666158 TI - Routine pulmonary function test can estimate the extent of tuberculous destroyed lung. AB - Tuberculous destroyed lung (TDL) is diagnosed by a clear past history of tuberculosis with findings of parenchymal destruction verified by chest X-ray. Despite the resultant deterioration of lung function and quality of lives seen in TDL patients, the exact mechanism or characteristics of pulmonary function worsening have not been clearly studied. We investigated the feature of respiratory impairment of TDL patients, and studied whether extent of destroyed lung measured with chest CT has any correlation with routine lung function. To evaluate the degree of destruction, the Goddard classification scoring system was modified into a novel scoring system (destroyed lung score, (DLS)) with a score from 0 to 4. Twenty-five subjects were enrolled. TDL predominantly manifested as an obstructive pattern (64%, 16/25). Median value of DLS of the entire lung was 2.6 (1.7-3.9). Absolute values of FEV1 and FVC were both negatively associated with DLS (r = -0.78, P = 0.001, and r = -0.61, P = 0.021). Percentage of predicted value of FEV1 and FVC were also negatively associated with DLS (r = 0.62, P = 0.019, and r = -0.76, P = 0.002). Our study shows that lung function of TDL patients were notably correlated with the extent of destroyed lung measured with chest CT scan. PMID- 22666159 TI - Trace level arsenic quantification through cloud point extraction: application to biological and environmental samples. AB - A sensitive solvent-free extraction protocol for the quantification of arsenic at trace level has been described. It is based on the reaction of arsenic (V) with molybdate in acidic medium in presence of antimony (III) and ascorbic acid as a reducing agent to form a blue-colored arsenomolybdenum blue complex. The complex has been extracted into surfactant phase using Triton X-114, and its absorbance was measured at 690 nm. The detection limit, working range, and the relative standard deviation were found to be 1 ng mL-1, 10-200 ng mL-1, and 1.2%, respectively. The effect of common ions was studied, and the method has been applied to determine trace levels of As(III) and As(V) from a variety of samples like environmental, biological, and commercially procured chemicals. PMID- 22666161 TI - The confluence of Faraday's and Kirchoff's laws in bioelectrochemical systems. AB - When external measurements are made of electrochemical systems, including bioelectrochemical, there results an interaction. Such measurements cause electrochemical processes to take place that are significant. This work looks into the nature and significance of the interfacial processes on membrane and membrane phenomena. The conclusion reached is that interfacial processes are important and cannot be overlooked. PMID- 22666160 TI - Rapid prototyping in orthopaedic surgery: a user's guide. AB - Rapid prototyping (RP) is applicable to orthopaedic problems involving three dimensions, particularly fractures, deformities, and reconstruction. In the past, RP has been hampered by cost and difficulties accessing the appropriate expertise. Here we outline the history of rapid prototyping and furthermore a process using open-source software to produce a high fidelity physical model from CT data. This greatly mitigates the expense associated with the technique, allowing surgeons to produce precise models for preoperative planning and procedure rehearsal. We describe the method with an illustrative case. PMID- 22666163 TI - Rodent damage to natural and replanted mountain forest regeneration. AB - Impact of small rodents on mountain forest regeneration was studied in National Nature Reserve in the Beskydy Mountains (Czech Republic). A considerable amount of bark damage was found on young trees (20%) in spring after the peak abundance of field voles (Microtus agrestis) in combination with long winter with heavy snowfall. In contrast, little damage to young trees was noted under high densities of bank voles (Myodes glareolus) with a lower snow cover the following winter. The bark of deciduous trees was more attractive to voles (22% damaged) than conifers (8%). Young trees growing in open and grassy localities suffered more damage from voles than those under canopy of forest stands (chi2 = 44.04, P < 0.001). Natural regeneration in Nature Reserve was less damaged compared to planted trees (chi2 = 55.89, P < 0.001). The main factors influencing the impact of rodent species on tree regeneration were open, grassy habitat conditions, higher abundance of vole species, tree species preferences- and snow-cover condition. Under these conditions, the impact of rodents on forest regeneration can be predicted. Foresters should prefer natural regeneration to the artificial plantings. PMID- 22666162 TI - Characterization of mononucleated human peripheral blood cells. AB - Unspecialized cells that can renew themselves and give rise to multiple differentiated cell types are termed stem cells. The objective of this study was to characterize and investigate, through molecular and biochemical analyses, the stemness of cells derived from isolated mononucleated cells that originated from peripheral blood. The isolated mononucleated cells were separated according to their physical characteristics (adherent and suspension), after 4 to 7 days into a 14-day culturing period in complete medium. Our results revealed that adherent and suspension cells were positive for mesenchymal stem cell (MSC) and hematopoietic stem cell (HSC) markers, respectively. Differentiation of adherent cells into osteoblasts was associated with expression of the OPN gene and increasing ALP enzyme activity, while differentiation of suspension cells into osteoclasts was associated with expression of the TRAP gene and increasing TRAP enzyme activity. In conclusion, molecular and biochemical analyses showed that mononucleated cells consist of MSC (adherent) and HSC (suspension), and both cell types are able to differentiate into specialized cells from their respective lineage: osteoblast (MSC) and osteoclast (HSC). PMID- 22666164 TI - Isotopic and elemental determination in some romanian apple fruit juices. AB - H, C, O stable isotope ratios and the content of some heavy elements of 31 Romanian single-strength organic apple juices collected from four Transylvanian areas are discussed in this study. The aim of this study was to measure the 2H/1H, 18O/16O, 13C/12C ratios of these juices and their elemental profile and to establish a database of authentic values to be used for adulteration and authenticity testing. Our results have shown mean values of delta18O = -4.20/00 and deltaDdelta-46.50/00, respectively, for apples from Transylvania and at the same time the mean value of delta13C = -28.20/00. The content of Cd, Pb, U, Zn, As was below the acceptable limits stipulated in US-EPA standard for drinking water. Cu and Cr limits exceeded for one single juice; Ni content for some apple juices from Maramures, Alba, and Cluj was higher than the acceptable value. PMID- 22666165 TI - Identification and mechanism of Echinochloa crus-galli resistance to fenoxaprop-p ethyl with respect to physiological and anatomical differences. AB - Identification and mechanism of Echinochloa crus-galli (L.) resistance to fenoxaprop-p-ethyl via physiological and anatomical differences between susceptible and resistant were investigated. The physiological and anatomical differences that were take into account were growth reduction, chlorophyll content reduction, lamina thickness, and xylem vessel diameter in both susceptible and resistant biotypes of E. crus-galli. The results showed that the growth reduction fifty (GR50) of resistant biotype was 12.07-times higher than that of the susceptible biotype of E. crus-galli treated with fenoxaprop-p-ethyl. The chlorophyll content was highly reduced in the susceptible biotype relative to the resistant one of E. crus-galli treated with fenoxaprop-p-ethyl. An anatomical test showed significant differences in the cytology of susceptible and resistant biotypes of E. crus-galli treated with fenoxaprop-p-ethyl with respect to lamina thickness and xylem vessel diameter. The resistance of E. crus-galli to fenoxaprop-p-ethyl may be due to the faster metabolism of fenoxaprop-p-ethyl below the physiologically active concentration or the insensitivity of its target enzyme (Acetyl-CoA carboxylase). PMID- 22666166 TI - Physiological and growth responses of six turfgrass species relative to salinity tolerance. AB - The demand for salinity-tolerant turfgrasses is increasing due to augmented use of effluent or low-quality water (sea water) for turf irrigation and the growing turfgrass industry in coastal areas. Experimental plants, grown in plastic pots filled with a mixture of river sand and KOSAS(R) peat (9 : 1), were irrigated with sea water at different dilutions imparting salinity levels of 0, 8, 16, 24, 32, 40, or 48 dS m-1. Salinity tolerance was evaluated on the basis of leaf firing, shoot and root growth reduction, proline content, and relative water content. Paspalum vaginatum was found to be most salt tolerant followed by Zoysia japonica and Zoysia matrella, while Digitaria didactyla, Cynodon dactylon "Tifdwarf," and Cynodon dactylon "Satiri" were moderately tolerant. The results indicate the importance of turfgrass varietal selection for saline environments. PMID- 22666167 TI - Purification and characterization of hemagglutinating proteins from Poker-chip Venus (Meretrix lusoria) and Corbicula clam (Corbicula fluminea). AB - Hemagglutinating proteins (HAPs) were purified from Poker-chip Venus (Meretrix lusoria) and Corbicula clam (Corbicula fluminea) using gel-filtration chromatography on a Sephacryl S-300 column. The molecular weights of the HAPs obtained from Poker-chip Venus and Corbicula clam were 358 kDa and 380 kDa, respectively. Purified HAP from Poker-chip Venus yielded two subunits with molecular weights of 26 kDa and 29 kDa. However, only one HAP subunit was purified from Corbicula clam, and its molecular weight was 32 kDa. The two Poker chip Venus HAPs possessed hemagglutinating ability (HAA) for erythrocytes of some vertebrate animal species, especially tilapia. Moreover, HAA of the HAP purified from Poker-chip Venus was higher than that of the HAP of Corbicula clam. Furthermore, Poker-chip Venus HAPs possessed better HAA at a pH higher than 7.0. When the temperature was at 4 degrees C-10 degrees C or the salinity was less than 0.50/00, the two Poker-chip Venus HAPs possessed better HAA compared with that of Corbicula clam. PMID- 22666168 TI - One-pot synthesis of beta-acetamido ketones using boric acid at room temperature. AB - beta-acetamido ketones were synthesized in excellent yields through one-pot condensation reaction of aldehydes, acetophenones, acetyl chloride, and acetonitrile in the presence of boric acid as a solid heterogeneous catalyst at room temperature. It is the first successful report of boric acid that has been used as solid acid catalyst for the preparation of beta-acetamido ketones. The remarkable advantages offered by this method are green catalyst, mild reaction conditions, simple procedure, short reaction times, and good-to-excellent yields of products. PMID- 22666169 TI - Lipids and all-cause mortality among older adults: a 12-year follow-up study. AB - This is a 12-year follow-up cohort study with 800 people (60-85 years old). The association between lipid disorders and mortality was analysed by Cox proportional hazard adjusted model. All-cause mortality was considered the dependent variable, and lipid disorders as independent variables: total cholesterol (TC) >200 and <170 mg/dl, HDL-c <35 and 40, LDL-c >100 and 130, and triglycerides (TG) >50. An initial analysis of all subjects was performed and a second was carried out after having excluded individuals with a body mass index (BMI) <20 kg/m2 or mortality in <= 2 years. The mortality showed a positive association with low TC and a negative association with high TC and high LDL-c. After the exclusion of underweight and premature mortality, there was a positive association only with TC <170 mg/dl (HR = 1.36, CI95%: 1.02-1.82). The data did not show a higher risk with high levels of TC, LDL-c, and TG. However, they showed higher mortality among older adults with low TC. PMID- 22666171 TI - Oral vaccination based on DNA-chitosan nanoparticles against Schistosoma mansoni infection. AB - The development of a vaccine would be essential for the control of schistosomiasis, which is recognized as the most important human helminth infection in terms of morbidity and mortality. A new approach of oral vaccination with DNA-chitosan nanoparticles appears interesting because of their great stability and the ease of target accessibility, besides chitosan immunostimulatory properties. Here we described that chitosan nanoparticles loaded with plasmid DNA encoding Rho1-GTPase protein of Schistosoma mansoni, prepared at different molar ratios of primary amines to DNA phosphate anion (N/P), were able to complex electrostatically with DNA and condense it into positively charged nanostructures. Nanoparticles were able to maintain zeta potential and size characteristics in media that simulate gastric (SGF) and intestinal fluids (SIF). Further in vivo studies showed that oral immunization was not able to induce high levels of specific antibodies but induced high levels of the modulatory cytokine IL-10. This resulted in a significative reduce of liver pathology, although it could not protect mice of infection challenge with S. mansoni worms. Mice immunized only with chitosan nanoparticles presented 47% of protection against parasite infection, suggesting an important role of chitosan in inducing a protective immune response against schistosomiasis, which will be more explored in further studies. PMID- 22666170 TI - Biology and biotechnology of follicle development. AB - Growth and development of ovarian follicles require a series of coordinated events that induce morphological and functional changes within the follicle, leading to cell differentiation and oocyte development. The preantral early antral follicle transition is the stage of follicular development during which gonadotropin dependence is obtained and the progression into growing or atresia of the follicle is made. Follicular growth during this period is tightly regulated by oocyte-granulosatheca cell interactions. A cluster of early expressed genes is required for normal folliculogenesis. Granulosa cell factors stimulate the recruitment of theca cells from cortical stromal cells. Thecal factors promote granulosa cell proliferation and suppress granulosa cell apoptosis. Cell-cell and cell-extracellular matrix interactions influence the production of growth factors in the different follicular compartments (oocyte, granulosa, and theca cells). Several autocrine and paracrine factors are involved in follicular growth and differentiation; their activity is present even at the time of ovulation, decreasing the gap junction communication, and stimulating the theca cell proliferation. In addition, the identification of the factors that promote follicular growth from the preantral stage to the small antral stage may provide important information for the identification for assisted reproduction techniques. PMID- 22666172 TI - Effects of ginseng and echinacea on cytokine mRNA expression in rats. AB - The aim of the study was to determine the effect of ginseng and echinacea on the mRNA expression of IL-10, TNF-alpha, and TGF-beta1 in healthy rats. Six-week-old male Fischer 344 rats (n = 48) were used. The animals were divided into three equal groups, as follows: control (C); ginseng (G); echinacea (E). While the C group was fed a standard rat diet (Purina) ad libitum for a period of 40 days, the G and E groups animals received the same diet containing 0.5 g/kg of Panax ginseng root powder and 0.75 g/kg of Echinacea purpurea root powder, respectively. Blood samples were obtained from 8 rats in each group after 20 and 40 days of treatment, and the mRNA expression of IL-10, TNF-alpha, and TGF-beta1 was determined. After 20 days of treatment, the expression of IL-10 mRNA in the G group was different from the C group (P < 0.05); however, after 40 days of treatment, there was no difference between the groups. There was no difference after 20 and 40 days of treatment between the groups with respect to the expression of TGF-beta1 mRNA. After 20 days of treatment, the expression of TNF alpha mRNA in the E group was higher (P < 0.05) than the C group. After 40 days of treatment, the expression of TNF-alpha mRNA was similar in all of the groups. Based on the current study, the increase in expression of IL-10 mRNA in the G group and the increase in expression of TNF-alpha mRNA in the E group support the use of these plants for purposes of modulating the immune system. However, a more detailed study regarding the effects of ginseng and echinacea on these cytokines and other cytokines is needed. PMID- 22666174 TI - A learning-based approach for biomedical word sense disambiguation. AB - In the biomedical domain, word sense ambiguity is a widely spread problem with bioinformatics research effort devoted to it being not commensurate and allowing for more development. This paper presents and evaluates a learning-based approach for sense disambiguation within the biomedical domain. The main limitation with supervised methods is the need for a corpus of manually disambiguated instances of the ambiguous words. However, the advances in automatic text annotation and tagging techniques with the help of the plethora of knowledge sources like ontologies and text literature in the biomedical domain will help lessen this limitation. The proposed method utilizes the interaction model (mutual information) between the context words and the senses of the target word to induce reliable learning models for sense disambiguation. The method has been evaluated with the benchmark dataset NLM-WSD with various settings and in biomedical entity species disambiguation. The evaluation results showed that the approach is very competitive and outperforms recently reported results of other published techniques. PMID- 22666173 TI - Risk factors for infection with different hepatitis C virus genotypes in southern Brazil. AB - OBJECTIVES: To investigate the proportion of different genotypes in countryside microregions in southern Brazil, and their association with risk factors. METHODS: Cross-sectional study including a convenience sample of patients who tested positive for HCV-RNA and were referred to a regional health center for genotyping, from December 2003 to January 2008. Data were obtained through the National Disease Surveillance Data System, from laboratory registers and from patient charts. Identification of genotypes was carried out using the Restriction Fragment Length Polymorphism "in house" technique. Independent associations with genotypes were evaluated in multinomial logistic regression and prevalence rates of genotypes were estimated with modified Poisson regression. RESULTS: The sample consisted of 441 individuals, 41.1 +/- 12.0 years old, 56.5% men. Genotype 1 was observed in 41.5% (95% CI 37.9-48.1) of patients, genotype 2 in 19.3% (95% CI 15.0-23.6), and genotype 3 in 39.2% (95% CI 35.6-43.0). HCV genotype was significantly associated with gender and age. Dental procedures were associated with higher proportion of genotype 2 independently of age, education, and patient treatment center. CONCLUSIONS: The hepatitis C virus genotype 1 was the most frequent. Genotype 2 was associated with female gender, age, and dental procedure exposition. PMID- 22666175 TI - Photoinduced synthesis of new diisochromenochromen-4-ones and their antimicrobial activities. AB - The diisochromenochromen-4-one 3a-3b, 4a-4c, 5a-6a & 7 have been prepared from the photocyclization reaction of bischromen-4-one 2a-2e. The later compounds are obtained from the O-alkylation of the suitable 3-hydroxy-2-aryl-4H-chromen-4-one 1a-1e with 4,4'-bischloromethyl-diphenyl in dry acetone, anhydrous K2CO3, and PTC (Bu4N+I-) under refluxing conditions. The structures of compounds 2a-2e, 3a-3b, 4a-4c, 5a-6a & 7 have been characterized from the rigorous analysis of their IR, 1H-NMR, 13C-NMR, ESI-Mass, and elemental analysis. The antibacterial and antifungal activities of the synthesized products were also evaluated against the Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Bacillus subtilis, and Aspergillus janus and Penicillium glabrum, respectively. Some of the tested compounds showed significant activity against the above-said microorganisms. PMID- 22666176 TI - Emotional competence as a positive youth development construct: a conceptual review. AB - The concept of emotional competence as a positive youth development construct is reviewed in this paper. Differences between emotional intelligence and emotional competence are discussed and an operational definition is adopted. Assessment methods of emotional competence with an emphasis on its quantitative nature are introduced. In the discussion of theories of emotional competence, the functionalist and developmental perspectives and the relationships with positive youth development are highlighted. Possible antecedents, especially the influence of early child-caregiver, and expected outcomes of emotional competence are examined. Practical ways to promote emotional competence among adolescents, particularly the role of parents and teachers, and the future direction of research are also discussed. PMID- 22666179 TI - Single-molecule technique links structural fluctuations of proteins to brain diseases. PMID- 22666177 TI - Arabidopsis thaliana-Aphid Interaction. AB - Aphids are important pests of plants that use their stylets to tap into the sieve elements to consume phloem sap. Besides the removal of photosynthates, aphid infestation also alters source-sink patterns. Most aphids also vector viral diseases. In this chapter, we will summarize on recent significant findings in plant-aphid interaction, and how studies involving Arabidopsis thaliana and Myzus persicae (Sulzer), more commonly known as the green peach aphid (GPA), are beginning to provide important insights into the molecular basis of plant defense and susceptibility to aphids. The recent demonstration that expression of dsRNA in Arabidopsis can be used to silence expression of genes in GPA has further expanded the utility of Arabidopsis for evaluating the contribution of the aphid genome-encoded proteins to this interaction. PMID- 22666180 TI - Dealing with data: a case study on information and data management literacy. PMID- 22666178 TI - Common features at the start of the neurodegeneration cascade. AB - Amyloidogenic neurodegenerative diseases are incurable conditions with high social impact that are typically caused by specific, largely disordered proteins. However, the underlying molecular mechanism remains elusive to established techniques. A favored hypothesis postulates that a critical conformational change in the monomer (an ideal therapeutic target) in these "neurotoxic proteins" triggers the pathogenic cascade. We use force spectroscopy and a novel methodology for unequivocal single-molecule identification to demonstrate a rich conformational polymorphism in the monomer of four representative neurotoxic proteins. This polymorphism strongly correlates with amyloidogenesis and neurotoxicity: it is absent in a fibrillization-incompetent mutant, favored by familial-disease mutations and diminished by a surprisingly promiscuous inhibitor of the critical monomeric beta-conformational change, neurotoxicity, and neurodegeneration. Hence, we postulate that specific mechanostable conformers are the cause of these diseases, representing important new early-diagnostic and therapeutic targets. The demonstrated ability to inhibit the conformational heterogeneity of these proteins by a single pharmacological agent reveals common features in the monomer and suggests a common pathway to diagnose, prevent, halt, or reverse multiple neurodegenerative diseases. PMID- 22666181 TI - Stepped care for maternal mental health: a case study of the perinatal mental health project in South Africa. AB - As one article in a series on Global Mental Health Practice, Simone Honikman and colleagues from South Africa provide a case study of the Perinatal Mental Health Project, which delivered mental health care to pregnant women in a collaborative, step-wise manner, making use of existing resources in primary care. PMID- 22666182 TI - Prevalence and risk of violence and the physical, mental, and sexual health problems associated with human trafficking: systematic review. AB - BACKGROUND: There is very limited evidence on the health consequences of human trafficking. This systematic review reports on studies investigating the prevalence and risk of violence while trafficked and the prevalence and risk of physical, mental, and sexual health problems, including HIV, among trafficked people. METHODS AND FINDINGS: We conducted a systematic review comprising a search of Medline, PubMed, PsycINFO, EMBASE, and Web of Science, hand searches of reference lists of included articles, citation tracking, and expert recommendations. We included peer-reviewed papers reporting on the prevalence or risk of violence while trafficked and/or on the prevalence or risk of any measure of physical, mental, or sexual health among trafficked people. Two reviewers independently screened papers for eligibility and appraised the quality of included studies. The search identified 19 eligible studies, all of which reported on trafficked women and girls only and focused primarily on trafficking for sexual exploitation. The review suggests a high prevalence of violence and of mental distress among women and girls trafficked for sexual exploitation. The random effects pooled prevalence of diagnosed HIV was 31.9% (95% CI 21.3%-42.4%) in studies of women accessing post-trafficking support in India and Nepal, but the estimate was associated with high heterogeneity (I2 = 83.7%). Infection prevalence may be related as much to prevalence rates in women's areas of origin or exploitation as to the characteristics of their experience. Findings are limited by the methodological weaknesses of primary studies and their poor comparability and generalisability. CONCLUSIONS: Although limited, existing evidence suggests that trafficking for sexual exploitation is associated with violence and a range of serious health problems. Further research is needed on the health of trafficked men, individuals trafficked for other forms of exploitation, and effective health intervention approaches. PMID- 22666183 TI - Improving access to mental health care and psychosocial support within a fragile context: a case study from Afghanistan. AB - As one article in a series on Global Mental Health Practice, Peter Ventevogel and colleagues provide a case study of their efforts to integrate brief, practice oriented mental health training into the Afghanistan health care system at a time when the system was being rebuilt from scratch. PMID- 22666185 TI - Evaluating a traditional medicine policy in South Africa: phase 1 development of a policy assessment tool. AB - BACKGROUND: Policies that empower individuals and communities may be appropriate for public health, and more broadly. Simple, transparent and acceptable tools are therefore required to evaluate policies from an empowerment perspective. In 2008, the South African Department of Health (DOHSA) drafted a policy to endorse the integration of African Traditional Medicine (ATM) into the public health sector, following the World Health Organization's (WHO) long-standing directives. OBJECTIVE: The purpose of this study is to critically analyze this policy using a novel evaluation tool. DESIGN: A 12-point 'Policy Empowerment Index' (PEI) is introduced, and used to classify and score the policy according to five theoretical policy types. The evaluation was based on a stepwise review and associated publications: policy drafts, policy statements and news announcements. RESULTS: According to the assessment tool, the ATM policy was marginally 'supportive' of constituent empowerment, although several 'directive' features were also observed. The importance of ATM to SA's communities and the promotion of education, employment, entrepreneurship and peripheral resource mobilization were the main empowering elements. Centralised conception, planning and implementation, the absence of provisions for local adaptations and the authoritative legislation context were sub-optimal features. CONCLUSIONS: South Africa's ATM legislation may need to further involve communities in policy design and implementation to capitalise upon the broader benefits of community empowerment. However, the iterative nature of method and evaluation is important. Indeed, they are proposed as points to initiate participatory development, and improve policy evaluation. Such instruments can empower constituents in the political process. PMID- 22666186 TI - Genetically encoded proton sensors reveal activity-dependent pH changes in neurons. AB - The regulation of hydrogen ion concentration (pH) is fundamental to cell viability, metabolism, and enzymatic function. Within the nervous system, the control of pH is also involved in diverse and dynamic processes including development, synaptic transmission, and the control of network excitability. As pH affects neuronal activity, and can also itself be altered by neuronal activity, the existence of tools to accurately measure hydrogen ion fluctuations is important for understanding the role pH plays under physiological and pathological conditions. Outside of their use as a marker of synaptic release, genetically encoded pH sensors have not been utilized to study hydrogen ion fluxes associated with network activity. By combining whole-cell patch clamp with simultaneous two-photon or confocal imaging, we quantified the amplitude and time course of neuronal, intracellular, acidic transients evoked by epileptiform activity in two separate in vitro models of temporal lobe epilepsy. In doing so, we demonstrate the suitability of three genetically encoded pH sensors: deGFP4, E(2)GFP, and Cl-sensor for investigating activity-dependent pH changes at the level of single neurons. PMID- 22666187 TI - Synaptic clustering during development and learning: the why, when, and how. AB - To contribute to a functional network a neuron must make specific connections and integrate the synaptic inputs that it receives in a meaningful way. Previous modeling and experimental studies have predicted that this specificity could entail a subcellular organization whereby synapses that carry similar information are clustered together on local stretches of dendrite. Recent imaging studies have now, for the first time, demonstrated synaptic clustering during development and learning in different neuronal circuits. Interestingly, this organization is dependent on synaptic activity and most likely involves local plasticity mechanisms. Here we discuss these new insights and give an overview of the candidate plasticity mechanisms that could be involved. PMID- 22666188 TI - Functional expression of the GABA(A) receptor alpha2 and alpha3 subunits at synapses between intercalated medial paracapsular neurons of mouse amygdala. AB - In the amygdala, GABAergic neurons in the intercalated medial paracapsular cluster (Imp) have been suggested to play a key role in fear learning and extinction. These neurons project to the central (CE) amygdaloid nucleus and to other areas within and outside the amygdala. In addition, they give rise to local collaterals that innervate other neurons in the Imp. Several drugs, including benzodiazepines (BZ), are allosteric modulators of GABA(A) receptors. BZ has both anxiolytic and sedative actions, which are mediated through GABA(A) receptors containing alpha2/alpha3 and alpha1 subunits, respectively. To establish whether alpha1 or alpha2/alpha3 subunits are expressed at Imp cell synapses, we used paired recordings of anatomically identified Imp neurons and high resolution immunocytochemistry in the mouse. We observed that a selective alpha3 subunit agonist, TP003 (100 nM), significantly increased the decay time constant of the unitary IPSCs. A similar effect was also induced by zolpidem (10 MUM) or by diazepam (1 MUM). In contrast, lower doses of zolpidem (0.1-1 MUM) did not significantly alter the kinetics of the unitary IPSCs. Accordingly, immunocytochemical experiments established that the alpha2 and alpha3, but not the alpha1 subunits of the GABA(A) receptors, were present at Imp cell synapses of the mouse amygdala. These results define, for the first time, some of the functional GABA(A) receptor subunits expressed at synapses of Imp cells. The data also provide an additional rationale to prompt the search of GABA(A) receptor alpha3 selective ligands as improved anxiolytic drugs. PMID- 22666190 TI - Center-surround vs. distance-independent lateral connectivity in the olfactory bulb. AB - Lateral neuronal interactions are known to play important roles in sensory information processing. A center-on surround-off local circuit arrangement has been shown to play a role in mediating contrast enhancement in the visual, auditory, and somatosensory systems. The lateral connectivity and the influence of those connections have been less clear for the olfactory system. A critical question is whether the synaptic connections between the primary projection neurons, mitral and tufted (M/T) cells, and their main inhibitory interneurons, the granule cells (GCs), can support a center-surround motif. Here, we study this question by injecting a "center" in the glomerular layer of the olfactory bulb (OB) with a marker of synaptic connectivity, the pseudorabies virus (PRV), then examines the distribution of labeling in the "surround" of GCs. We use a novel method to score the degree to which the data fits a center-surround model vs. distance-independent connectivity. Data from 22 injections show that M/T cells generally form lateral connections with GCs in patterns that lie between the two extremes. PMID- 22666189 TI - Postnatal maturation of somatostatin-expressing inhibitory cells in the somatosensory cortex of GIN mice. AB - Postnatal inhibitory neuron development affects mammalian brain function, and failure of this maturation process may underlie pathological conditions such as epilepsy, schizophrenia, and depression. Furthermore, understanding how physiological properties of inhibitory neurons change throughout development is critical to understanding the role(s) these cells play in cortical processing. One subset of inhibitory neurons that may be affected during postnatal development is somatostatin-expressing (SOM) cells. A subset of these cells is labeled with green-fluorescent protein (GFP) in a line of mice known as the GFP positive inhibitory neurons (GIN) line. Here, we studied how intrinsic electrophysiological properties of these cells changed in the somatosensory cortex of GIN mice between postnatal ages P11 and P32+. GIN cells were targeted for whole-cell current-clamp recordings and ranges of positive and negative current steps were presented to each cell. The results showed that as the neocortical circuitry matured during this critical time period multiple intrinsic and firing properties of GIN inhibitory neurons, as well as those of excitatory (regular-spiking [RS]) cells, were altered. Furthermore, these changes were such that the output of GIN cells, but not RS cells, increased over this developmental period. We quantified changes in excitability by examining the input-output relationship of both GIN and RS cells. We found that the firing frequency of GIN cells increased with age, while the rheobase current remained constant across development. This created a multiplicative increase in the input-output relationship of the GIN cells, leading to increases in gain with age. The input output relationship of the RS cells, on the other hand, showed primarily a subtractive shift with age, but no substantial change in gain. These results suggest that as the neocortex matures, inhibition coming from GIN cells may become more influential in the circuit and play a greater role in the modulation of neocortical activity. PMID- 22666192 TI - Cortical GABAergic neurons: stretching it. PMID- 22666191 TI - Molecular analysis of ivy cells of the hippocampal CA1 stratum radiatum using spectral identification of immunofluorophores. AB - Neuronal nitric oxide synthase-expressing (nNOS+) GABAergic interneurons are common in hippocampal stratum (str.) radiatum. However, these cells are less well characterized than nNOS+ ivy cells in str. pyramidale or neurogliaform cells (NGC) in str. lacunosum-moleculare. Here we have studied the laminar distribution of the axons and dendrites, and the immunoreactivity of these neurons recorded in rat hippocampal slices. We have used spectral analysis of antibody- or streptavidin-conjugated fluorophores to improve recognition of genuine signals in reactions for molecules such as nNOS and neuropeptide-Y (NPY). We found that most nNOS+ cells with soma in the CA1 area str. radiatum exhibit characteristic properties of ivy cells, and were positive for NPY and negative for reelin. However, laminar distributions of their neurites differ from original characterization of ivy cells with the soma in or close to str. pyramidale. Both their dendrites and axon are mainly in str. radiatum and to a lesser extent in str. oriens, and in addition often extend to str. lacunosum-moleculare. We conclude that ivy cells in str. radiatum may predominantly be feedforward inhibitory interneurons in the CA1 area, and their axonal output delivering GABA, NPY, and NO can influence both the entorhinal cortex innervated and the CA3 innervated zones pre- and post-synaptically. Spectral analysis of fluorophores provides an objective algorithm to analyze signals in immunoreactions for neurochemical markers. PMID- 22666193 TI - Gap prepulse inhibition and auditory brainstem-evoked potentials as objective measures for tinnitus in guinea pigs. AB - Tinnitus or ringing of the ears is a subjective phantom sensation necessitating behavioral models that objectively demonstrate the existence and quality of the tinnitus sensation. The gap detection test uses the acoustic startle response elicited by loud noise pulses and its gating or suppression by preceding sub startling prepulses. Gaps in noise bands serve as prepulses, assuming that ongoing tinnitus masks the gap and results in impaired gap detection. This test has shown its reliability in rats, mice, and gerbils. No data exists for the guinea pig so far, although gap detection is similar across mammals and the acoustic startle response is a well-established tool in guinea pig studies of psychiatric disorders and in pharmacological studies. Here we investigated the startle behavior and prepulse inhibition (PPI) of the guinea pig and showed that guinea pigs have a reliable startle response that can be suppressed by 15 ms gaps embedded in narrow noise bands preceding the startle noise pulse. After recovery of auditory brainstem response (ABR) thresholds from a unilateral noise over exposure centered at 7 kHz, guinea pigs showed diminished gap-induced reduction of the startle response in frequency bands between 8 and 18 kHz. This suggests the development of tinnitus in frequency regions that showed a temporary threshold shift (TTS) after noise over-exposure. Changes in discharge rate and synchrony, two neuronal correlates of tinnitus, should be reflected in altered ABR waveforms, which would be useful to objectively detect tinnitus and its localization to auditory brainstem structures. Therefore, we analyzed latencies and amplitudes of the first five ABR waves at suprathreshold sound intensities and correlated ABR abnormalities with the results of the behavioral tinnitus testing. Early ABR wave amplitudes up to N3 were increased for animals with tinnitus possibly stemming from hyperactivity and hypersynchrony underlying the tinnitus percept. Animals that did not develop tinnitus after noise exposure showed the opposite effect, a decrease in wave amplitudes for the later waves P4 P5. Changes in latencies were only observed in tinnitus animals, which showed increased latencies. Thus, tinnitus-induced changes in the discharge activity of the auditory nerve and central auditory nuclei are represented in the ABR. PMID- 22666194 TI - Representation of numerosity in posterior parietal cortex. AB - Humans and animals appear to share a similar representation of number as an analog magnitude on an internal, subjective scale. Neurological and neurophysiological data suggest that posterior parietal cortex (PPC) is a critical component of the circuits that form the basis of numerical abilities in humans. Patients with parietal lesions are impaired in their ability to access the deep meaning of numbers. Acalculiac patients with inferior parietal damage often have difficulty performing arithmetic (2 + 4?) or number bisection (what is between 3 and 5?) tasks, but are able to recite multiplication tables and read or write numerals. Functional imaging studies of neurologically intact humans performing subtraction, number comparison, and non-verbal magnitude comparison tasks show activity in areas within the intraparietal sulcus (IPS). Taken together, clinical cases and imaging studies support a critical role for parietal cortex in the mental manipulation of numerical quantities. Further, responses of single PPC neurons in non-human primates are sensitive to the numerosity of visual stimuli independent of low-level stimulus qualities. When monkeys are trained to make explicit judgments about the numerical value of such stimuli, PPC neurons encode their cardinal numerical value; without such training PPC neurons appear to encode numerical magnitude in an analog fashion. Here we suggest that the spatial and integrative properties of PPC neurons contribute to their critical role in numerical cognition. PMID- 22666195 TI - Electrophysiological correlates of predictive coding of auditory location in the perception of natural audiovisual events. AB - In many natural audiovisual events (e.g., a clap of the two hands), the visual signal precedes the sound and thus allows observers to predict when, where, and which sound will occur. Previous studies have reported that there are distinct neural correlates of temporal (when) versus phonetic/semantic (which) content on audiovisual integration. Here we examined the effect of visual prediction of auditory location (where) in audiovisual biological motion stimuli by varying the spatial congruency between the auditory and visual parts. Visual stimuli were presented centrally, whereas auditory stimuli were presented either centrally or at 90 degrees azimuth. Typical sub-additive amplitude reductions (AV - V < A) were found for the auditory N1 and P2 for spatially congruent and incongruent conditions. The new finding is that this N1 suppression was greater for the spatially congruent stimuli. A very early audiovisual interaction was also found at 40-60 ms (P50) in the spatially congruent condition, while no effect of congruency was found on the suppression of the P2. This indicates that visual prediction of auditory location can be coded very early in auditory processing. PMID- 22666196 TI - Not so fast: taste stimulus coding time in the rat revisited. AB - Behavioral and electrophysiological studies suggest that rats can identify a taste stimulus with a single lick, in <200 ms. However, the conditions under which these conclusions were drawn varied widely across experiments. We designed a series of experiments to assess the effects of the number of licks of a tastant that are available, tastant concentration and prior learning experience on the speed with which a tastant can modify behavior. To accomplish this we tested exemplars of four basic taste qualities (quinine, 0.1 mM; NaCl, 100 mM; saccharin, 4 mM, or sucrose, 100 mM; citric acid, 10 mM) in rats that were conditioned to avoid quinine. Taste stimuli were available for one, two, or three licks on separate days. All tastants were presented in a randomized order interspersed with water rinse licks presented on a variable ratio schedule. A tastant-specific significant increase in the proportion of long pauses in licking following quinine presentation was defined as evidence of "behavioral identification." Rats with aversion training given three licks of all taste stimuli paused significantly more often after quinine by the fourth interlick interval, ~580 ms. Control rats showed no evidence of quinine (0.1 mM) identification. When rats in all conditioning groups were tested with a high concentration of quinine (10 mM), a single lick was sufficient to produce significant pausing after quinine, but not until the fourth interlick interval, i.e., ~580 ms. Testing rats with only two tastants rather than four in a session had no effect on the speed of quinine identification. Present data confirm that a single lick is sufficient for rats to identify a taste stimulus, but that additional licks occur before evidence of identification is apparent. Furthermore, learning, tastant concentration and motivation to drink can all modify the speed of behavioral identification. PMID- 22666198 TI - Autologous immune enhancement therapy in recurrent ovarian cancer with metastases: a case report. AB - Current therapeutic modalities for ovarian cancer such as chemotherapy, radiotherapy and surgery have been reported to yield only marginal success in improving survival rates of patients and have associated adverse effects. We report here a case of recurrent stage IV ovarian cancer, treated with cell-based autologous immune enhancement therapy (AIET) along with chemotherapy and followed up for 18 months. A 54-year-old female was diagnosed with a recurrence of ovarian carcinoma 1 year after initial surgical removal followed by chemotherapy for stage IIIC ovarian carcinoma. When diagnosed in 2010 with recurrence, she had liver and spleen metastases with a CA-125 level of 243 U/ml and a stage IV clinical status. Six infusions of AIET using autologous in vitro expanded and activated natural killer (NK) cells (CD3-CD56+) and activated T lymphocytes (CD3+CD56+) were administered in combination with 6 cycles of chemotherapy with carboplatin and doxorubicin. Following this treatment, CA-125 decreased to 4.7 U/ml along with regression of the metastatic lesions and an improved quality of life. No adverse reactions were reported after the AIET transfusions. Eighteen months of follow-up revealed a static nonprogressive disease. Combining AIET with chemotherapy and other conventional treatments has been found to be effective in our experience, as reported earlier, even in patients with advanced ovarian cancer, and we recommend this strategy be considered in treating similar cases. PMID- 22666199 TI - Plasmacytoma of the nasolacrimal duct simulating dacryocystitis: an uncommon presentation for extramedullary relapse of multiple myeloma. AB - The most common site for localized forms of plasma cell neoplasms (extramedullary plasmacytoma; EMP) is the upper respiratory tract, including the oropharynx, nasal cavities, sinuses and larynx. A 50-year-old woman with a history of myeloma in complete remission after autologous stem cell transplantation complained of two weeks of epiphora of the left eye with subsequent diplopia, bloody nasal discharge and progressive swelling around the nasolacrimal sac. A solitary mass in the left sinonasal area, extending to the nasolacrimal duct (NLD) was detected on MRI, whose histopathological examination was consistent with plasmacytoma. Further clinical investigation ruled out multiple myeloma (MM). The patient underwent debulking surgery and adjuvant chemotherapy followed by local radiotherapy in an attempt to achieve complete response. Despite being a rare entity, EMP of the NLD should be considered in the differential diagnosis of epiphora and dacryocystitis. To our knowledge, this is the first case of a plasmacytoma of the NLD presenting as isolated extramedullary relapse of MM. The follow-up in EMPs should include appropriate imaging studies, a systemic workup to rule out MM. PMID- 22666197 TI - Patients with Schizophrenia Fail to Up-Regulate Task-Positive and Down-Regulate Task-Negative Brain Networks: An fMRI Study Using an ICA Analysis Approach. AB - Recent research suggests that the cerebral correlates of cognitive deficits in schizophrenia are nested in the activity of widespread, inter-regional networks rather than being restricted to any specific brain location. One of the networks that have received focus lately is the default mode network. Parts of this network have been reported as hyper-activated in schizophrenia patients (SZ) during rest and during task performance compared to healthy controls (HC), although other parts have been found to be hypo-activated. In contrast to this network, task-positive networks have been reported as hypo-activated compared in SZ during task performance. However, the results are mixed, with, e.g., the dorsolateral prefrontal cortex showing both hyper- and hypo-activation in SZ. In this study we were interested in signal increase and decrease differences between a group of SZ and HC in cortical networks, assuming that the regulatory dynamics of alternating task-positive and task-negative neuronal processes are aberrant in SZ. We compared 31 SZ to age- and gender-matched HC, and used fMRI and independent component analysis (ICA) in order to identify relevant networks. We selected the independent components (ICs) with the largest signal intensity increases (STG, insula, supplementary motor cortex, anterior cingulate cortex, and MTG) and decreases (fusiform gyri, occipital lobe, PFC, cingulate, precuneus, and angular gyrus) in response to a dichotic auditory cognitive task. These ICs were then tested for group differences. Our findings showed deficient up regulation of the executive network and a corresponding deficit in the down regulation of the anterior default mode, or effort network during task performance in SZ when compared with HC. These findings may indicate a deficit in the dynamics of alternating task-dependent and task-independent neuronal processes in SZ. The results may cast new light on the mechanisms underlying cognitive deficits in schizophrenia, and may be of relevance for diagnostics and new treatments. PMID- 22666200 TI - Trastuzumab-induced myocardiotoxicity mimicking acute coronary syndrome. AB - Trastuzumab is an important biological agent in the treatment of HER2-positive breast cancer, with effects on response rates, progression-free survival, overall survival and quality of life. Although this drug is well tolerated in terms of adverse effects, trastuzumab-associated myocardiotoxicity has been described to have an incidence of 0.6-4.5% and in rare cases, the drug can trigger severe congestive heart failure with progression to death or even mimic acute coronary syndrome with complete left bundle branch blockade. In this paper is reported a case of trastuzumab-associated myocardiotoxicity manifesting as acute coronary syndrome in a 69-year-old female. The patient is currently undergoing a conservative clinical treatment that restricts overexertion.The majority of clinical studies report trastuzumab-induced cardiotoxicity as a rare event, and, when present, characterized by mild to moderate clinical signs, the ease of reversibility with pharmacological measures and the temporary discontinuation of the medication. Conversely, it is vital for the oncologist/cardiologist to consider the possibility that trastuzumab-induced cardiotoxicity may manifest itself as a severe clinical case, mimicking acute coronary syndrome, justifying careful risk stratification and adequate cardiac monitoring, especially in high risk patients. PMID- 22666201 TI - Rituximab and cytokine release syndrome. AB - Rituximab is a biologic agent that is usually well tolerated. With its increasing use for a myriad of rheumatologic and immunologic conditions, post-marketing surveillance has revealed more side effects. Systemic inflammatory response syndrome associated with cytokine release syndrome (CRS) is a very rare entity associated with the use of rituximab and carries a very high morbidity and case fatality rate. Cases of CRS reported within the literature are of patients with a very high tumor burden leading to a catastrophic cascade of events. We report the case of a patient having post-transplant lymphoproliferative disorder who died of fatal lactic acidosis and CRS within 24 h of receiving rituximab. Understanding the pathophysiology of such cases and identifying patients at risk may help to possibly avert this life-threatening complication. PMID- 22666202 TI - Carboplatin-induced hypersensitivity reaction. AB - We describe a 65-year-old female with relapsed ovarian cancer who developed a severe hypersensitivity reaction during the second cycle of carboplatin treatment. The patient developed respiratory failure, acute respiratory distress syndrome and hypotension, requiring admission to the intensive care unit. PMID- 22666203 TI - Normal pressure hydrocephalus as an unusual presentation of supratentorial extraventricular space-occupying processes: report on two cases. AB - Normal pressure hydrocephalus (NPH) is a clinical and radiographic syndrome characterized by ventriculomegaly, abnormal gait, urinary incontinence, and dementia. The condition may occur due to a variety of secondary causes but may be idiopathic in approximately 50% of patients. Secondary causes may include head injury, subarachnoid hemorrhage, meningitis, and central nervous system tumor. Here, we describe two extremely rare cases of supratentorial extraventricular space-occupying processes: meningioma and glioblastoma multiforme, which initially presented with NPH. PMID- 22666204 TI - Bladder Carcinoma after ABVD Chemotherapy for Hodgkin's Lymphoma: A Case Report. AB - The treatment of lymphomas may result in the development of second malignancies, as evident by the numerous reports in the literature. Treatment with cyclophosphamide-based chemotherapy regimens may lead to bladder lesions such as haemorrhagic cystitis and also to carcinoma of the urinary bladder. Previous pelvic radiotherapy treatment is also implicated as a cause for local second cancers. We present the case of a patient treated for Hodgkin's lymphoma, who was diagnosed with transitional cell carcinoma of the bladder soon after treatment completion. On completion of 6 cycles of ABVD chemotherapy the patient was on follow-up. Two months after treatment completion the patient complained of dysuria and was investigated for a suspected urinary tract infection. Urine microscopy did not reveal any abnormality. Symptomatic treatment was prescribed and cystoscopy was arranged. The cystoscopic findings suggested an irregular growth overlying the trigone and the biopsy reported it as transitional cell carcinoma. This case report demonstrates that symptoms attributed to common medical causes in patients treated for cancer may be a sign of second malignancy. This case report also demonstrates the need for a thorough evaluation of patients' complaints during follow-up, although the likelihood for the occurrence of a second malignancy may be low. The assumption that these symptoms were due to a commonly occurring urinary tract infection would have had serious implications leading to a delay in the treatment of the bladder cancer. PMID- 22666205 TI - Successful Treatment of Advanced Metastatic Prostate Cancer following Chemotherapy Based on Molecular Profiling. AB - After Taxotere fails, treatment options for metastatic prostate cancer are limited. The three drugs with FDA approval in this setting, Jevtana, Provenge and Zytiga, are associated with median survivals of less than 2 years. In part, the impact on survival is the result of low response rates, indicating a significant proportion of patients exhibiting de novo resistance to these agents. An alternate approach is to let treatment selection be governed by gene expression profiling so that the treatment is tailored to the specific patient. Here, we report a case of metastatic prostate cancer with a dramatic response to treatment selected based on molecular profiling. This patient had failed LHRH agonist, bicalutamide, Taxotere, and doxorubicin. Molecular profiling showed overexpression of the androgen receptor and he had a dramatic response of measurable disease to second-line hormonal therapy with ketoconazole, estrogen and Leukine. PMID- 22666206 TI - Meningeal Hemangiopericytoma with Intracranial Metastases in an HIV-Positive Male: Case Report and Review of the Literature. AB - BACKGROUND: Meningeal hemangiopericytoma is a rare, aggressive CNS tumor that tends to invade locally, metastasize, and has a high rate of recurrence. HIV classically increases the risk of 3 AIDS-defining malignancies: Kaposi's sarcoma, non-Hodgkin's lymphoma and invasive cervical cancer. More recently, considerable interest has been paid to the link between HIV and a wider range of non-AIDS defining cancers. An HIV-positive patient with meningeal hemangiopericytoma is described. CASE DESCRIPTION: A 36-year-old HIV-positive male presented with worsening headache and ataxia. The patient had experienced similar neurologic symptoms 4 months prior and MRI at that time had showed an extra-axial left cerebellar mass most consistent with benign meningioma. Repeat MRI showed the tumor had increased in size by a factor of greater than 20 in this 4-month period, with 4 small additional foci of similar enhancement. Subtotal resection was performed on the mass and final pathological diagnosis was meningeal hemangiopericytoma. CONCLUSIONS: This represents the first reported case of meningeal hemangiopericytoma in an HIV-positive patient. This is also the shortest time to intracranial metastasis ever reported for a meningeal hemangiopericytoma. Although the increased risk in the HIV-positive population of non-AIDS-defining cancers that has been observed in recent years can largely be attributed to cancers with a known viral pathogenesis, it is speculated that HIV infection in this patient may have contributed to the occurrence or unique behavior of this rare tumor. PMID- 22666207 TI - Synchronous primary adenocarcinoma and ancient schwannoma in the colon: an unusual case report. AB - Gastrointestinal schwannomas are uncommon stromal tumors of the intestinal tract and colon schwannomas are extremely rare. We report a rare case of ascending colon schwannoma with associated synchronous adenocarcinoma of the sigmoid colon. A 68-year-old man presented with a 20-day history of bleeding per rectum. Colonoscopy revealed a mass of 4.2 cm in diameter with endoluminal protrusion in the sigmoid colon and a second submucosal tumor in the ascending colon. Surgical intervention was suggested and ileo-hemicolectomy was done. Microscopically, the submucosal tumor of 4 cm in diameter showed features of schwannoma with degenerative change (ancient schwannoma). Lesional cells were positive for S100p and negative for actin, desmin, CD34, CD117, and pankeratin. The mass showed features of an invasive moderately differentiated adenocarcinoma. Colon schwannoma is a rare submucosal tumor, and the incidental occurrence with adenocarcinoma has not been well described in the literature. PMID- 22666208 TI - Prolonged Complete Response after GEMOX Chemotherapy in a Patient with Advanced Fibrolamellar Hepatocellular Carcinoma. AB - The only currently validated treatment for advanced hepatocellular carcinoma (HCC) is sorafenib. However, sorafenib has been mainly studied in patients with HCC developed in cirrhotic liver. Chemotherapy might be more suitable for patients with HCC in non-cirrhotic liver. We report the case of a young woman with fibrolamellar HCC in a non-cirrhotic liver, with histologically proven metastatic ganglionary relapse after surgical resection of the primary tumour. Chemotherapy with gemcitabine and oxaliplatin (GEMOX regimen) achieved a complete response without relapse five years after discontinuation of chemotherapy. This exceptional case raises the question of clinical trials specifically designed for patients with HCC in non-cirrhotic liver. PMID- 22666209 TI - Paclitaxel plus Carboplatin Chemotherapy for Primary Peritoneal Carcinoma: A Study of 22 Cases and Comparison with Stage III-IV Ovarian Serous Carcinoma. AB - The aim of this study was to assess the clinical characteristics and outcome of patients with either primary peritoneal carcinoma (PPC) or ovarian serous carcinoma (OSC) treated with paclitaxel plus carboplatin chemotherapy. We retrospectively identified 22 PPC patients and 55 stage III-IV OSC patients treated between 2002 and 2007. After exploratory laparotomy, all patients received paclitaxel and carboplatin every 3 weeks, with the goal of optimal cytoreduction. There were no statistically significant differences between the PPC and OSC groups with regard to tumor stage, residual tumor after debulking surgery (initial or interval), serum cancer antigen (CA) 125 levels at diagnosis, and completion of first-line chemotherapy. The progression-free survival (PFS) durations were 12.7 months (95% CI, 6.3-18.5) in the patients with PPC and 15.9 months (95% CI, 13.3-18.5) in those with OSC (p = 0.016). However, the median survival durations were 26.5 months (95% CI, 14.6-38.3) in the patients with PPC and 38 months (95% CI, 23.8-53.8) in those with OSC (p = 0.188). Survival was longer for all patients whose CA125 levels normalized to 26 U/ml during and after treatment. Overall survival (OS) of the patients with PPC was similar to that of the patients with OSC, suggesting that management for advanced-stage OSC would be similar to that for PPC. The combination of optimal debulking with paclitaxel plus carboplatin chemotherapy may offer patients the most effective treatment. The CA125 nadir after cytoreductive surgery can be considered a prognostic factor for OS and PFS in patients with PPC. PMID- 22666210 TI - PSA Response to Lenalidomide Therapy in a Pre-Treated Patient with Metastatic Prostate Cancer Refractory to Hormones and Chemotherapy: A Case Report. AB - Hormone-resistant prostate cancer (HRPC) occurs when prostate cancer is no longer responsive to hormone therapy. Treatment options are limited, and there is a clear necessity for therapies that improve outcome. Preclinical and clinical evidence supports the role of the immunomodulatory agent lenalidomide in HRPC. In this paper, we report that lenalidomide showed antitumoral activity in a patient with HRPC and bone metastases pre-treated with chemotherapy, decreased the PSA level and improved the patient's health status for the first 5 months. It is important to emphasize that it was not associated with hematologic toxicity. PMID- 22666211 TI - Solitary fibrous tumor in the round ligament of the liver: a fortunate intraoperative discovery. AB - Solitary fibrous tumors (SFTs) are mesenchymal neoplasms of fibroblastic origin, most commonly found in the pleura. Numerous extrathoracic locations have been reported during the last 2 decades. Herein, we report the first case of an SFT in the round ligament of the liver. A 46-year-old Caucasian man presented with a 12 month history of abdominal pain. An ultrasonography-guided microbiopsy first revealed a desmoid tumor. After failure of first- and second-line medical treatments (celecoxib and tamoxifen, then imatinib), histological reexamination was suspicious for a low-grade sarcoma. MRI was also suspicious for a malignant process. Hence, surgery was decided. Laparotomy found a huge and well-limited tumor that, unexpectedly, was appended to the round ligament of the liver and free from any other intra-abdominal contact. The tumor was easily removed. Excision was monobloc and macroscopically complete. Histological analysis diagnosed an SFT arising from the round ligament of the liver. No adjuvant treatment was given. Ten months after surgery, the patient is alive without any signs or symptoms of relapse. This is the first report of SFT arising from the round ligament of the liver. It illustrates the difficulty in diagnosing such tumors. Whilst diagnosis of SFT is rare, it should be kept in mind to allow early diagnosis and complete surgical resection, which provide the best chance for recovery. PMID- 22666212 TI - Effects of aging and anatomic location on gene expression in human retina. AB - OBJECTIVE: To determine the effects of age and topographic location on gene expression in human neural retina. METHODS: Macular and peripheral neural retina RNA was isolated from human donor eyes for DNA microarray and quantitative RT-PCR analyses. RESULTS: Total RNA integrity from human donors was preserved. Hierarchical clustering analysis demonstrates that the gene expression profiles of young, old, macula, and peripheral retina cluster into four distinct groups. Genes which are highly expressed in macular, peripheral, young, or old retina were identified, including inhibitors of Wnt Signaling Pathway (DKK1, FZD10, and SFRP2) which are preferably expressed in the periphery. CONCLUSION: The transcriptome of the human retina is affected by age and topographic location. Wnt pathway inhibitors in the periphery may maintain peripheral retinal cells in an undifferentiated state. Understanding the effects of age and topographic location on gene expression may lead to the development of new therapeutic interventions for age-related eye diseases. PMID- 22666214 TI - Cortical oscillations in auditory perception and speech: evidence for two temporal windows in human auditory cortex. AB - Natural sounds, including vocal communication sounds, contain critical information at multiple time scales. Two essential temporal modulation rates in speech have been argued to be in the low gamma band (~20-80 ms duration information) and the theta band (~150-300 ms), corresponding to segmental and diphonic versus syllabic modulation rates, respectively. It has been hypothesized that auditory cortex implements temporal integration using time constants closely related to these values. The neural correlates of a proposed dual temporal window mechanism in human auditory cortex remain poorly understood. We recorded MEG responses from participants listening to non-speech auditory stimuli with different temporal structures, created by concatenating frequency-modulated segments of varied segment durations. We show that such non-speech stimuli with temporal structure matching speech-relevant scales (~25 and ~200 ms) elicit reliable phase tracking in the corresponding associated oscillatory frequencies (low gamma and theta bands). In contrast, stimuli with non-matching temporal structure do not. Furthermore, the topography of theta band phase tracking shows rightward lateralization while gamma band phase tracking occurs bilaterally. The results support the hypothesis that there exists multi-time resolution processing in cortex on discontinuous scales and provide evidence for an asymmetric organization of temporal analysis (asymmetrical sampling in time, AST). The data argue for a mesoscopic-level neural mechanism underlying multi-time resolution processing: the sliding and resetting of intrinsic temporal windows on privileged time scales. PMID- 22666213 TI - GABAergic circuit dysfunctions in neurodevelopmental disorders. AB - GABAergic interneurons control neuronal excitability, integration, and plasticity. Further, they regulate the generation of temporal synchrony and oscillatory behavior among networks of pyramidal neurons. Such oscillations within and across neural systems are believed to serve various complex functions, such as perception, movement initiation, and memory. Alterations in the development of GABAergic circuits have been implicated in various brain diseases with neurodevelopmental origin. Here, we highlight recent studies suggesting a role for alterations of GABA transmission in the pathophysiology of two neurodevelopmental diseases, schizophrenia, and autism. We further discuss how manipulations of GABA signaling may be used for novel therapeutic interventions. PMID- 22666215 TI - Developmental plasticity in child growth and maturation. AB - The ability of a given genotype to produce different phenotypes in response to different environments is termed "plasticity," and is part of the organism's "adaptability" to environmental cues. The expressions of suites of genes, particularly during development or life history transitions, probably underlie the fundamental plasticity of an organism. Plasticity in developmental programming has evolved in order to provide the best chances of survival and reproductive success to organisms under changing environments. Environmental conditions that are experienced in early life can profoundly influence human biology, child growth and maturation, and long-term health and longevity. Developmental origins of health and disease and life history transitions are purported to use placental, nutritional, and endocrine cues for setting long-term biological, mental, and behavioral strategies for child growth and maturation in response to local ecological and/or social conditions. The window of developmental plasticity extends from conception to early childhood, and even beyond to the transition from juvenility to adolescence, and could be transmitted transgenerationally. It involves epigenetic responses to environmental changes, which exert their effects during life history phase transitions. PMID- 22666216 TI - Mapping the follicle-stimulating hormone-induced signaling networks. AB - Follicle-stimulating hormone (FSH) is a central regulator of male and female reproductive function. Over the last decade, there has been a growing perception of the complexity associated with FSH-induced cellular signaling. It is now clear that the canonical Gs/cAMP/PKA pathway is not the sole mechanism that must be considered in FSH biological actions. In parallel, consistent with the emerging concept of biased agonism, several examples of ligand-mediated selective signaling pathway activation by gonadotropin receptors have been reported. In this context, it is important to gain an integrative view of the signaling pathways induced by FSH and how they interconnect to form a network. In this review, we propose a first attempt at building topological maps of various pathways known to be involved in the FSH-induced signaling network. We discuss the multiple facets of FSH-induced signaling and how they converge to the hormone integrated biological response. Despite of their incompleteness, these maps of the FSH-induced signaling network represent a first step toward gaining a system level comprehension of this hormone's actions, which may ultimately facilitate the discovery of novel regulatory processes and therapeutic strategies for infertility and non-steroidal contraception. PMID- 22666217 TI - Emerging targeted therapies for castration-resistant prostate cancer. AB - Until recently, few therapeutic options were available for patients with castration-resistant prostate cancer (CRPC). Since 2010, four new molecules with a demonstrated benefit (sipuleucel-T, cabazitaxel, abiraterone, and denosumab) have been approved in this setting, and to-date several other agents are under investigation in clinical trials. The purpose of this review is to present an update of targeted therapies for CRPC. Presented data are obtained from literature and congress reports updated until December 2011. Targeted therapies in advanced phases of clinical development include novel androgen signaling inhibitors, inhibitors of alternative signaling pathways, anti-angiogenic agents, inhibitors that target the bone microenvironment, and immunotherapeutic agents. Radium-223 and MDV3100 demonstrated a survival advantage in phase III trials and the road for their introduction in clinical practice is rapidly ongoing. Results are also awaited for phase III studies currently underway or planned with new drugs given as monotherapy (TAK-700, cabozantinib, tasquinimod, PROSTVAC-VF, ipilimumab) or in combination with docetaxel (custirsen, aflibercept, dasatinib, zibotentan). The optimal timing, combination, and sequencing of emerging therapies remain unknown and require further investigation. Additionally, the identification of novel markers of response and resistance to these therapies may better individualize treatment for patients with CRPC. PMID- 22666218 TI - Archaea in organic-lean and organic-rich marine subsurface sediments: an environmental gradient reflected in distinct phylogenetic lineages. AB - Examining the patterns of archaeal diversity in little-explored organic-lean marine subsurface sediments presents an opportunity to study the association of phylogenetic affiliation and habitat preference in uncultured marine Archaea. Here we have compiled and re-analyzed published archaeal 16S rRNA clone library datasets across a spectrum of sediment trophic states characterized by a wide range of terminal electron-accepting processes. Our results show that organic lean marine sediments in deep marine basins and oligotrophic open ocean locations are inhabited by distinct lineages of archaea that are not found in the more frequently studied, organic-rich continental margin sediments. We hypothesize that different combinations of electron donor and acceptor concentrations along the organic-rich/organic-lean spectrum result in distinct archaeal communities, and propose an integrated classification of habitat characteristics and archaeal community structure. PMID- 22666220 TI - Selection of Yeasts as Starter Cultures for Table Olives: A Step-by-Step Procedure. AB - The selection of yeasts intended as starters for table olives is a complex process, including a characterization step at laboratory level and a validation at lab level and factory-scale. The characterization at lab level deals with the assessment of some technological traits (growth under different temperatures and at alkaline pHs, effect of salt, and for probiotic strains the resistance to preservatives), enzymatic activities, and some new functional properties (probiotic traits, production of vitamin B-complex, biological debittering). The paper reports on these traits, focusing both on their theoretical implications and lab protocols; moreover, there are some details on predictive microbiology for yeasts of table olives and on the use of multivariate approaches to select suitable starters. PMID- 22666219 TI - Modes of retrotransposition of long interspersed element-1 by environmental factors. AB - Approximately 42% of the human genome is composed of endogenous retroelements, and the major retroelement component, long interspersed element-1 (L1), comprises ~17% of the total genome. A single human cell has more than 5 * 10(5) copies of L1, 80~100 copies of which are competent for retrotransposition (RTP). Notably, L1 can induce RTP of other retroelements, such as Alu and SVA, and is believed to function as a driving force of evolution. Although L1-RTP during early embryogenesis has been highlighted in the literature, recent observations revealed that L1-RTP also occurs in somatic cells. However, little is known about how environmental factors induce L1-RTP. Here, we summarize our current understanding of the mechanism of L1-RTP in somatic cells. We have focused on the mode of L1-RTP that is dependent on the basic helix-loop-helix/per-arnt-sim (bHLH/PAS) family of transcription factors. Along with the proposed function of bHLH/PAS proteins in environmental adaptation, we discuss the functional linking of L1-RTP and bHLH/PAS proteins for environmental adaptation and evolution. PMID- 22666221 TI - Microbial Iron(II) Oxidation in Littoral Freshwater Lake Sediment: The Potential for Competition between Phototrophic vs. Nitrate-Reducing Iron(II)-Oxidizers. AB - The distribution of neutrophilic microbial iron oxidation is mainly determined by local gradients of oxygen, light, nitrate and ferrous iron. In the anoxic top part of littoral freshwater lake sediment, nitrate-reducing and phototrophic Fe(II)-oxidizers compete for the same e(-) donor; reduced iron. It is not yet understood how these microbes co-exist in the sediment and what role they play in the Fe cycle. We show that both metabolic types of anaerobic Fe(II)-oxidizing microorganisms are present in the same sediment layer directly beneath the oxic anoxic sediment interface. The photoferrotrophic most probable number counted 3.4.10(5) cells.g(-1) and the autotrophic and mixotrophic nitrate-reducing Fe(II) oxidizers totaled 1.8.10(4) and 4.5.10(4) cells.g(-1) dry weight sediment, respectively. To distinguish between the two microbial Fe(II) oxidation processes and assess their individual contribution to the sedimentary Fe cycle, littoral lake sediment was incubated in microcosm experiments. Nitrate-reducing Fe(II) oxidizing bacteria exhibited a higher maximum Fe(II) oxidation rate per cell, in both pure cultures and microcosms, than photoferrotrophs. In microcosms, photoferrotrophs instantly started oxidizing Fe(II), whilst nitrate-reducing Fe(II)-oxidizers showed a significant lag-phase during which they probably use organics as e(-) donor before initiating Fe(II) oxidation. This suggests that they will be outcompeted by phototrophic Fe(II)-oxidizers during optimal light conditions; as phototrophs deplete Fe(II) before nitrate-reducing Fe(II) oxidizers start Fe(II) oxidation. Thus, the co-existence of the two anaerobic Fe(II)-oxidizers may be possible due to a niche space separation in time by the day-night cycle, where nitrate-reducing Fe(II)-oxidizers oxidize Fe(II) during darkness and phototrophs play a dominant role in Fe(II) oxidation during daylight. Furthermore, metabolic flexibility of Fe(II)-oxidizing microbes may play a paramount role in the conservation of the sedimentary Fe cycle. PMID- 22666222 TI - Role of the Aryl Hydrocarbon Receptor in Controlling Maintenance and Functional Programs of RORgammat(+) Innate Lymphoid Cells and Intraepithelial Lymphocytes. AB - Mucosal retinoic receptor-related orphan receptor (ROR)gammat-expressing innate lymphoid cells (ILC) play an important role in the defense against intestinal pathogens and in promoting epithelial homeostasis and adaptation, thereby effectively protecting the vertebrate host against intestinal inflammatory disorders. The functional activity of RORgammat(+) ILC is under the control of environmental cues. However, the molecular sensors for such environmental signals are largely unknown. Recently, the aryl hydrocarbon receptor (AhR) has emerged as a master regulator for the postnatal maintenance of intestinal RORgammat(+) ILC and intraepithelial lymphocytes. AhR is a highly conserved transcription factor whose activity is regulated by environmental and dietary small molecule ligands. Here, we review the role of AhR signaling for the maintenance of intestinal immune cells and its impact on the immunological protection against intestinal infections and debilitating chronic inflammatory disorders. PMID- 22666223 TI - HSP: Bystander Antigen in Atopic Diseases? AB - Over the last years insight in the complex interactions between innate and adaptive immunity in the regulation of an inflammatory response has increased enormously. This has revived the interest in stress proteins; proteins that are expressed during cell stress. As these proteins can attract and trigger an immunological response they can act as important mediators in this interaction. In this respect, of special interest are proteins that may act as modulators of both innate and adaptive immunity. Heat shock proteins (HSPs) are stress proteins that have these, and more, characteristics. More than two decades of studies on HSPs has revealed that they are part of intrinsic, "natural" mechanisms that steer inflammation. This has provoked comprehensive explorations of the role of HSPs in various human inflammatory diseases. Most studies have focused on classical autoimmune diseases. This has led to the development of clinical studies with HSPs that have shown promise in Phase II/III clinical trials. Remarkably, only very little is yet known of the role of HSPs in atopic diseases. In allergic disease a number of studies have investigated the possibility that allergen-specific regulatory T cell (Treg) function is defective in individuals with allergic diseases. This raises the question whether methods can be identified to improve the Treg repertoire. Studies from other inflammatory diseases have suggested HSPs may have such a beneficial effect on the T cell repertoire. Based on the immune mechanisms of atopic diseases, in this review we will argue that, as in other human inflammatory conditions, understanding immunity to HSPs is likely also relevant for atopic diseases. Specifically, we will discuss why certain HSPs such as HSP60 connect the immune response to environmental antigens with regulation of the inflammatory response. Thus they provide a molecular link that may eventually even help to better understand the immune pathological basis of the hygiene hypothesis. PMID- 22666224 TI - Rapid Maize Leaf and Immature Ear Responses to UV-B Radiation. AB - Because of their sessile lifestyle, plants have evolved adaptations to environmental factors, including UV-B present in solar radiation. To gain a better understanding of the initial events in UV-B acclimation, we have analyzed a 10 min to 1 h time course of transcriptome responses in irradiated and shielded leaves, and immature maize ears to unravel the systemic physiological and developmental responses in exposed and shielded organs. After 10 min of UV-B exposure, 262 transcripts are changed by at least two-fold in irradiated leaves, and this number doubles after 1 h. Indicative of the rapid modulation of transcription, 130 transcripts are only changed after 10 min. This is true not only in irradiated leaves, but also in shielded tissues. After 10 min of exposure, the overlap in transcriptome changes in irradiated and shielded organs is significant; however, after 30 min of UV-B, there are only two transcripts showing similar UV-B regulation between the three organs; 35 are similarly regulated in both IL and SL. Therefore, at longer irradiation times, there is more specificity of responses, and these are organ-specific. We suggest that early signaling in different tissues may be elicited by common signaling pathways, while at longer exposure times responses become more specific. To identify metabolites as possible signaling molecules, we looked for compounds that increased within 5-90 min in both irradiated and shielded leaves, to explain the kinetics of profound transcript changes within 1 h. We found that myoinositol is one such candidate metabolite; and we also demonstrate that if 0.1 mM myoinositol is applied to leaves of greenhouse maize, some metabolites that are changed by UV-B are also changed similarly by the chemical treatment. Therefore, this metabolite can partially mimic UV irradiation. PMID- 22666225 TI - Exploring the molecular and metabolic factors contributing to the adaptation of maize seedlings to nitrate limitation. AB - Crop production on soils containing sub-optimal levels of nitrogen (N) severely compromises yield potential. The development of plant varieties displaying high N use efficiency (NUE) will optimize N fertilizer use and reduce the environmental damage caused by excess N application. Maize is one of the most important crops cultivated worldwide. Identification of the genotypes with an enhanced NUE in the field is both time and resource consuming and sometime is difficult due to the regulation in the biotechnology programs. Identification of traits associated with adaptation to N limitation at an early vegetative stage which could reflect NUE at maturity is in need. We developed a hydroponic growth system and used it to test two genotypes that were different in their NUE at maturity under N limitation. One genotype SRG-200 showed a higher NUE than the other genotype SRG 100 and we used its hybrid SRG-150 as a reference for NUE. A number of phenotypic, molecular, and metabolic factors were tested using these three genetic lines at an early vegetative stage to determine which of these could be more indicative of predicting improved NUE at an early seedling stage. These include a transcriptional analysis which showed that the higher NUE in SRG-200 genotype is associated with higher transcript levels for the genes involved in nitrate transport, N assimilation, and GS and that the SRG-200 genotype maintained higher sugar content in leaves. Those identified in this study could be useful indicators for selecting promising maize lines at early stages to help develop elite varieties showing an enhanced NUE. PMID- 22666226 TI - Discolored1 (DSC1) is an ADP-Ribosylation Factor-GTPase Activating Protein Required to Maintain Differentiation of Maize Kernel Structures. AB - The embryo and endosperm are the products of double fertilization and comprise the clonally distinct products of angiosperm seed development. Recessive mutations in the maize gene discolored1 (dsc1) condition inviable seed that are defective in both embryo and endosperm development. Here, detailed phenotypic analyses illustrate that discolored mutant kernels are able to establish, but fail to maintain, differentiated embryo, and endosperm structures. Development of the discolored mutant embryo and endosperm is normal albeit delayed, prior to the abortion and subsequent degeneration of all differentiated kernel structures. Using a genomic fragment that was previously isolated by transposon tagging, the full length dsc1 transcript is identified and shown to encode an ADP-ribosylation factor-GTPase activating protein (ARF-GAP) that co-localizes with the trans-Golgi network/early endosomes and the plasma membrane during transient expression assays in N. benthamiana leaves. DSC1 function during endomembrane trafficking and the maintenance of maize kernel differentiation is discussed. PMID- 22666227 TI - Genetic, morphometric, and behavioral factors linked to the midsagittal area of the corpus callosum. AB - The corpus callosum is the main commissure connecting left and right cerebral hemispheres, and varies widely in size. Differences in the midsagittal area of the corpus callosum (MSACC) have been associated with a number of cognitive and behavioral phenotypes, including obsessive-compulsive disorders, psychopathy, suicidal tendencies, bipolar disorder, schizophrenia, autism, and attention deficit hyperactivity disorder. Although there is evidence to suggest that MSACC is heritable in normal human populations, there is surprisingly little evidence concerning the genetic modulation of this variation. Mice provide a potentially ideal tool to dissect the genetic modulation of MSACC. Here, we use a large genetic reference panel - the BXD recombinant inbred line - to dissect the natural variation of the MSACC. We estimated the MSACC in over 300 individuals from nearly 80 strains. We found a 4-fold difference in MSACC between individual mice, and a 2.5-fold difference among strains. MSACC is a highly heritable trait (h(2) = 0.60), and we mapped a suggestive QTL to the distal portion of Chr 14. Using sequence data and neocortical expression databases, we were able to identify eight positional and plausible biological candidate genes within this interval. Finally, we found that MSACC correlated with behavioral traits associated with anxiety and attention. PMID- 22666229 TI - Global Gene Expression Profiling in PPAR-gamma Agonist-Treated Kidneys in an Orthologous Rat Model of Human Autosomal Recessive Polycystic Kidney Disease. AB - Kidneys are enlarged by aberrant proliferation of tubule epithelial cells leading to the formation of numerous cysts, nephron loss, and interstitial fibrosis in polycystic kidney disease (PKD). Pioglitazone (PIO), a PPAR-gamma agonist, decreased cell proliferation, interstitial fibrosis, and inflammation, and ameliorated PKD progression in PCK rats (Am. J. Physiol.-Renal, 2011). To explore genetic mechanisms involved, changes in global gene expression were analyzed. By Gene Set Enrichment Analysis of 30655 genes, 13 of the top 20 downregulated gene ontology biological process gene sets and six of the top 20 curated gene set canonical pathways identified to be downregulated by PIOtreatment were related to cell cycle and proliferation, including EGF, PDGF and JNK pathways. Their relevant pathways were identified using the Kyoto Encyclopedia of Gene and Genomes database. Stearoyl-coenzyme A desaturase 1 is a key enzyme in fatty acid metabolism found in the top 5 genes downregulated by PIO treatment. Immunohistochemical analysis revealed that the gene product of this enzyme was highly expressed in PCK kidneys and decreased by PIO. These data show that PIO alters the expression of genes involved in cell cycle progression, cell proliferation, and fatty acid metabolism. PMID- 22666228 TI - The epigenetics of renal cell tumors: from biology to biomarkers. AB - Renal cell tumors (RCT) collectively constitute the third most common type of genitourinary neoplasms, only surpassed by prostate and bladder cancer. They comprise a heterogeneous group of neoplasms with distinctive clinical, morphological, and genetic features. Epigenetic alterations are a hallmark of cancer cells and their role in renal tumorigenesis is starting to emerge. Aberrant DNA methylation, altered chromatin remodeling/histone onco-modifications and deregulated microRNA expression not only contribute to the emergence and progression of RCTs, but owing to their ubiquity, they also constitute a promising class of biomarkers tailored for disease detection, diagnosis, assessment of prognosis, and prediction of response to therapy. Moreover, due to their dynamic and reversible properties, those alterations represent a target for epigenetic-directed therapies. In this review, the current knowledge about epigenetic mechanisms and their altered status in RCT is summarized and their envisaged use in a clinical setting is also provided. PMID- 22666231 TI - Vascular stem and progenitor cells in diabetic complications. PMID- 22666233 TI - Advances in diagnosis and treatment of biliopancreatic diseases. PMID- 22666232 TI - Intensive treatment of cellulite based on physiopathological principles. AB - Aim. The aim of this paper is to report a novel intensive therapy of gynoid lipodystrophy (cellulite) based on a new hypothesis. Methods. Were evaluated in 10 patients with ages ranging between 25 and 59 years (mean 35.6 years) grade IV cellulite identified by clinical evaluation. Before initiating treatment, perimetry was performed at 5 cm intervals along both thighs, at the gluteal fold, 5, 10, and 15 cm above the gluteal fold, at the navel, and 5 cm above the navel. The patients were submitted to a 4-hour daily treatment session that consisted of manual and mechanical lymph drainage and cervical stimulation by the Godoy & Godoy technique adapted for the treatment of cellulite. After 10 sessions over two weeks, the patients were again evaluated. The paired t-test was utilized for statistical analysis with an alpha error of 5% (P value < 0.05). A reduction was identified at all of the measurement points (paired t-test; P value < 0.0001). Results. The mean reductions varied between 4.0 and 5.7 cm at the measurement points but reductions of more than 10 cm in perimeter were achieved in some patients. Conclusion. This technique involving lymphatic system stimulation is efficacious in the treatment of cellulite. PMID- 22666230 TI - Physiology and emerging biochemistry of the glucagon-like peptide-1 receptor. AB - The glucagon-like peptide-1 (GLP-1) receptor is one of the best validated therapeutic targets for the treatment of type 2 diabetes mellitus (T2DM). Over several years, the accumulation of basic, translational, and clinical research helped define the physiologic roles of GLP-1 and its receptor in regulating glucose homeostasis and energy metabolism. These efforts provided much of the foundation for pharmaceutical development of the GLP-1 receptor peptide agonists, exenatide and liraglutide, as novel medicines for patients suffering from T2DM. Now, much attention is focused on better understanding the molecular mechanisms involved in ligand induced signaling of the GLP-1 receptor. For example, advancements in biophysical and structural biology techniques are being applied in attempts to more precisely determine ligand binding and receptor occupancy characteristics at the atomic level. These efforts should better inform three dimensional modeling of the GLP-1 receptor that will help inspire more rational approaches to identify and optimize small molecule agonists or allosteric modulators targeting the GLP-1 receptor. This article reviews GLP-1 receptor physiology with an emphasis on GLP-1 induced signaling mechanisms in order to highlight new molecular strategies that help determine desired pharmacologic characteristics for guiding development of future nonpeptide GLP-1 receptor activators. PMID- 22666234 TI - Efficacy of a "Rescue" Ciprofloxacin-Based Regimen for Eradication of Helicobacter pylori Infection after Treatment Failures. AB - The aim of our study was to evaluate the efficacy and tolerability of a ciprofloxacin-based regimen for H. pylori eradication failures as an alternative to bismuth based quadruple therapy. Methods. DESIGN: prospective single-center study. Patients in whom a first eradication trial with omeprazole/esomeprazole, clarithromycin plus amoxicillin or tinidazole/metronidazole had failed were included. H. pylori status: established by histology, rapide urease test and polymerase chain reaction. INTERVENTION: esomeprazole 20 mg, ciprofloxacin 500 mg, and metronidazole 500 mg, administered together before breakfast and dinner for 10 days. Susceptibility testing was performed by the Epsilometer test. Ciprofloxacin resistance was defined as a MIC of >=1 MUg/mL. Eradication was established by a negative 13C-UBT and 4-6 weeks post-therapy. Efficacy and side effects were determined. Results. 34 patients were enrolled, 32 completed the study. Compliance was excellent (100%). Side effects were mild. Ciprofloxacin based therapy cured 65% (22/34) of patients by intention to treat and 69% (22/32) per protocol analysis. The prevalence of ciprofloxacin resistance was 8%. Conclusions. The effectiveness of ciprofloxacin-based therapy was greatly reduced despite the high prevalence of ciprofloxacin sensitive H. pylori strains. Bismuth based quadruple therapy still remain the best choice as a "rescue" regimen in our region. PMID- 22666235 TI - Surgical results of patients with peritoneal carcinomatosis treated with cytoreductive surgery using a new technique named aqua dissection. AB - During 2004 to 2011, 81, 420, and 166 patients with colorectal cancer (CRC), epithelial appendiceal neoplasm (APN), and gastric cancer (GC) with PC were treated with cytoreductive surgery (CRS) plus perioperative chemotherapy. CRS was performed by peritonectomy techniques using an aqua dissection. Results. Complete cytoreduction was done in 62/81 (76.5%), 228/420 (54.3%), and 101/166 (60.8%) of patients with CRC, APN, and GC. The main reasons of incomplete resections were involvement of all peritoneal regions and diffuse involvement of small bowel. The incidence (64%, 302/470) of CC-0 resection after introduction of an aqua dissection was significantly higher than before (42%, 82/197). A total of 41 (6.1%) patients died postoperatively. Major complication (grade 3-4 complications) occurred in 126 patients (18.9%). A reoperation was necessary in 36 patients (5.4%). By the multivariate analysis, PCI scores capable of serving as thresholds for favorable versus poor prognosis in each group and CC scores demonstrated as the independent prognostic factors. Conclusions. Peritonectomy using an aqua dissection improves the incidence of complete cytoreduction, and improves the survival of patients with PC. Patients with PCI larger than the threshold values should be treated with chemotherapy to improve the incidences of complete cytoreduction. PMID- 22666237 TI - Antinociceptive, anti-inflammatory, and antipyretic activity of mangrove plants: a mini review. AB - Mangrove plants are specialised plants that grow in the tidal coasts of tropic and subtropic regions of the world. Their unique ecology and traditional medicinal uses of mangrove plants have attracted the attention of researchers over the years, and as a result, reports on biological activity of mangrove plants have increased significantly in recent years. This review has been set out to compile and appraise the results on antinociceptive, anti-inflammatory, and antipyretic activity of mangrove plants. While the Web of Knowledge, Google Scholar, and PubMed were the starting points to gather information, other pieces of relevant published literature were also adequately explored for this purpose. A total of 29 reports on 17 plant species have been found to report such activities. While 19 reports were on the biological activity of the crude extracts, 10 reports identified the active compound(s) of various chemical classes of natural products including terpenes, steroids, and flavonoids. This review finds that antinociceptive, anti-inflammatory, and antipyretic activity appears to be widespread in mangrove plants. PMID- 22666236 TI - Disposition kinetics of taxanes in peritoneal dissemination. AB - Treatment of cancers in the abdominal cavity, such as peritoneal dissemination, is difficult, but in principle intraperitoneal administration of anticancer drugs is expected to be preferable to systemic administration. Taxane anticancer drugs are used to treat gastric cancer patients with peritoneal dissemination. They are administered as micellar preparations, Taxol and Taxotere, which consist of paclitaxel in Cremophor EL (crEL) and docetaxel in Polysorbate-80 (PS-80), respectively. In this paper we review the disposition kinetics of taxane anticancer drugs after intraperitoneal administration in peritoneal dissemination patients and animal models and also discuss the effect of the surfactant vehicle on the behavior of taxanes. PMID- 22666238 TI - New pathophysiological aspects of growth and prevention of kidney stones. AB - Kidney stones probably grow during crystalluria by crystal sedimentation and aggregation (AGN) on stone surfaces. This process has to occur within urinary transit time (UT) through the kidney before crystals are washed out by diuresis. To get more information, we studied by spectrophotometry the formation and AGN of Ca oxalate (Ca Ox) crystals which were directly produced in urine of 30 stone patients and 30 controls by an oxalate (Ox) titration. Some tests were also performed after removing urinary macromolecules (UMs) by ultrafiltration. To induce rapid crystallization, high Ox additions (0.5-0.8 mM) were necessary. The most important finding was retardation of crystal AGN by UM. In urine of 63% of controls but only 33% of patients, no AGN was observed during an observation of 60 minutes (P < 0.05). Also growth and sedimentation rate of crystals were significantly reduced by UM. For stone metaphylaxis, especially for posttreatment residuals, avoiding dietary Ox excesses to prevent crystal formation in the kidney and increasing diuresis to wash out crystals before they aggregate are recommended. PMID- 22666239 TI - Focal therapy, differential therapy, and radiation treatment for prostate cancer. AB - Focal and differential therapy represent an approach to improve the therapeutic ratio of prostate cancer treatments. This concept is a shift from treating the whole gland to intensely treating the portion of the gland that contains significant tumor. However, there are many challenges in the move towards focal approaches. Defining which patients are suitable candidates for focal therapy approaches is an area of significant controversy, and it is likely that additional data from imaging or detailed biopsy methods is needed in addition to traditional risk factors. A number of methods have been suggested, and imaging with multiparametric MRI and transperineal template mapping biopsy have shown promise. The approach of differential therapy where the entire prostate is treated to a lower intensity and the tumor areas to high intensity is also discussed in detail. Radiation therapy is a well suited modality for the delivery of differential therapy. Data in the literature using external beam radiation, high dose rate brachytherapy, and low-dose rate brachytherapy for differential therapy are reviewed. Preliminary results are encouraging, and larger studies and randomized controlled trials are needed to validate this approach. PMID- 22666240 TI - Focal laser ablation of prostate cancer: definition, needs, and future. AB - Current challenges and innovations in prostate cancer management concern the development of focal therapies that allow the treatment of only the cancer areas sparing the rest of the gland to minimize the potential morbidity. Among these techniques, focal laser ablation (FLA) appears as a potential candidate to reach the goal of focusing energy delivery on the identified targets. The aim of this study is to perform an up-to-date review of this new therapeutic modality. Relevant literature was identified using MEDLINE database with no language restrictions (entries: focal therapy, laser interstitial thermotherapy, prostate cancer, FLA) and by cross-referencing from previously identified studies. Precision, real-time monitoring, MRI compatibility, and low cost of integrated system are principal advantages of FLA. Feasibility and safety of this technique have been reported in phase I assays. FLA might eventually prove to be a middle ground between active surveillance and radical treatment. In conclusion, FLA may have found a role in the management of prostate cancer. However, further trials are required to demonstrate the oncologic effectiveness in the long term. PMID- 22666241 TI - Adherence to Guidelines among Italian Urologists on Imaging Preoperative Staging of Low-Risk Prostate Cancer: Results from the MIRROR (Multicenter Italian Report on Radical Prostatectomy Outcomes and Research) Study. AB - Objective. A number of evidence-based guidelines for diagnosis and management of prostate cancer have been published. The aim of this study is to evaluate the adherence of Italian urologists to the guidelines concerning the preoperative imaging staging of prostate cancer. Methods. In October 2007 a multicentric observational perspective study called Multicentric Italian Report on Radical prostatectomy Outcome and Research (MIRROR) was started in 135 Italian urology centers. Recruitment was closed in December 2008 and 2,408 cases were collected. In this paper we have taken into consideration all examinations carried out for preoperative imaging staging, evaluating compliance with the recommendations in the American Urological Association (AUA) and European Association of Urology (EAU) guidelines. Results. Five hundred sixty-seven (53.34%) patients were not managed according to the EAU guidelines concerning T-staging, 545 (51.27%) concerning N-staging and 757 (71.21%) concerning M-staging. According to AUA guidelines, we also analyzed patients with a Gleason grade of biopsy specimens of 7: 238 (57.35%) of these patients had undergone testing for T staging, 244 (57.35%) for N-staging and 322 (77.60%) for M-staging. Conclusions. The compliance of Italian urologists with the guidelines is low, leading to an inappropriate increase in cost of care and unnecessary anxiety for the patients. PMID- 22666242 TI - Transversus abdominis plane catheter bolus analgesia after major abdominal surgery. AB - Purpose. Transversus abdominis plane (TAP) blocks have been shown to reduce pain and opioid requirements after abdominal surgery. The aim of the present case series was to demonstrate the use of TAP catheter injections of bupivacaine after major abdominal surgery. Methods. Fifteen patients scheduled for open colonic resection surgery were included. After induction of anesthesia, bilateral TAP catheters were placed, and all patients received a bolus dose of 20 mL bupivacaine 2.5 mg/mL with epinephrine 5 MUg/mL through each catheter. Additional bolus doses were injected bilaterally 12, 24, and 36 hrs after the first injections. Supplemental pain treatment consisted of paracetamol, ibuprofen, and gabapentin. Intravenous morphine was used as rescue analgesic. Postoperative pain was rated on a numeric rating scale (NRS, 0-10) at regular predefined intervals after surgery, and consumption of intravenous morphine was recorded. Results. The TAP catheters were placed without any technical difficulties. NRS scores were <=3 at rest and <=5 during cough at 4, 8, 12, 18, 24, and 36 hrs after surgery. Cumulative consumption of intravenous morphine was 28 (23-48) mg (median, IQR) within the first 48 postoperative hours. Conclusion. TAP catheter bolus injections can be used to prolong analgesia after major abdominal surgery. PMID- 22666243 TI - Clinical Predictors of Mortality in Adults with Intellectual Disabilities with and without Down Syndrome. AB - Background. Mood, baseline functioning, and cognitive abilities as well as psychotropic medications may contribute to mortality in adults with and without Down Syndrome (DS). Methods. Population-based (nonclinical), community-dwelling adults with intellectual disabilities (IDs) were recruited between 1995 and 2000, assessed individually for 1-4 times, and then followed by yearly phone calls. Results. 360 participants (116 with DS and 244 without DS) were followed for an average of 12.9 years (range 0-16.1 years as of July 2011). 108 people died during the course of the followup, 65 males (31.9% of all male participants) and 43 females (27.6% of all female participants). Cox proportional hazards modeling showed that baseline practical skills, seizures, anticonvulsant use, depressive symptoms, and cognitive decline over the first six years all significantly contributed to mortality, as did a diagnosis of DS, male gender, and higher age at study entry. Analysis stratified by DS showed interesting differences in mortality predictors. Conclusion. Although adults with DS have had considerable improvements in life expectancy over time, they are still disadvantaged compared to adults with ID without DS. Recognition of potentially modifiable factors such as depression may decrease this risk. PMID- 22666244 TI - A topology-based metric for measuring term similarity in the gene ontology. AB - The wide coverage and biological relevance of the Gene Ontology (GO), confirmed through its successful use in protein function prediction, have led to the growth in its popularity. In order to exploit the extent of biological knowledge that GO offers in describing genes or groups of genes, there is a need for an efficient, scalable similarity measure for GO terms and GO-annotated proteins. While several GO similarity measures exist, none adequately addresses all issues surrounding the design and usage of the ontology. We introduce a new metric for measuring the distance between two GO terms using the intrinsic topology of the GO-DAG, thus enabling the measurement of functional similarities between proteins based on their GO annotations. We assess the performance of this metric using a ROC analysis on human protein-protein interaction datasets and correlation coefficient analysis on the selected set of protein pairs from the CESSM online tool. This metric achieves good performance compared to the existing annotation based GO measures. We used this new metric to assess functional similarity between orthologues, and show that it is effective at determining whether orthologues are annotated with similar functions and identifying cases where annotation is inconsistent between orthologues. PMID- 22666245 TI - Nervous System of Periplaneta americana Cockroach as a Model in Toxinological Studies: A Short Historical and Actual View. AB - Nervous system of Periplaneta americana cockroach is used in a wide range of pharmacological studies, including electrophysiological techniques. This paper presents its role as a preparation in the development of toxinological studies in the following electrophysiological methods: double-oil-gap technique on isolated giant axon, patch-clamp on DUM (dorsal unpaired median) neurons, microelectrode technique in situ conditions on axon in connective and DUM neurons in ganglion, and single-fiber oil-gap technique on last abdominal ganglion synapse. At the end the application of cockroach synaptosomal preparation is mentioned. PMID- 22666246 TI - Subchronic hepatotoxicity evaluation of 2,3,4,6-tetrachlorophenol in sprague dawley rats. AB - Male Sprague Dawley rats were exposed to 2,3,4,6-tetrachlorophenol (TCP) for 5 days, 2 weeks, 4 weeks, or 13 weeks. TCP was administered by gavage at doses of 0, 10, 25, 50, 100, or 200 mg/kg/day. Endpoints evaluated included clinical observations, body weights, liver weights, serum chemistry, blood TCP, gross pathology, and liver histopathology. There were no TCP exposure-related clinical signs of toxicity. Mean body weight decreased 12-22% compared to control in the 100 and 200 mg/kg/day groups. Serum ALT concentrations were increased in rats of the 200 mg/k/day. Liver weight increases were both dose- and exposure time related and statistically significant at >=25 mg/kg/day. Incidence and severity of centrilobular hepatocytic vacuolation, hepatocyte hypertrophy, and single cell hepatocytic necrosis were related to dose and exposure time. Following 13 weeks of exposure, bile duct hyperplasia and centrilobular and/or periportal fibrosis were observed in rats primarily of the highest TCP dose group. Blood TCP concentrations increased with dose and at 13 weeks ranged from 1.3 to 8.5 MUg/mL (10 to 200 mg/kg/day). A NOAEL of 10 mg/kg/day was selected based on the statistically significant incidence of hepatocyte hypertrophy at doses >=25 mg/kg/day. PMID- 22666247 TI - Interpretation of hormone levels in older patients: points for consideration. AB - Blood hormone and tumor marker concentrations are usually determined by immunochemical methods which are based on an unique reaction between antigen and assay capture antibody. Despite the speed and simplicity of assays performance on automatic immunochemistry platforms, the interpretation of final results requires a deep knowledge of method fallibility. General lack of immunoassays standardization, presence of cross-reacting substances in patient's sample, limitation of free hormones measurement due to abnormal analyte binding protein concentrations, assay interferences due to patient's autoantibodies, and heterophilic antibodies, as well as proper interpretation of very low- and very high-sample analyte levels, are the main points discussed in respect to hormones and tumor markers measurement in geriatric population. PMID- 22666248 TI - Role of phosphatidylinositol-3-kinase pathway in head and neck squamous cell carcinoma. AB - Activation of the phosphatidylinositol-3-kinase (PI3K) pathway is one of the most frequently observed molecular alterations in many human malignancies, including head and neck squamous cell carcinoma (HNSCC). A growing body of evidence demonstrates the prime importance of the PI3K pathway at each stage of tumorigenesis, that is, tumor initiation, progression, recurrence, and metastasis. Expectedly, targeting the PI3K pathway yields some promising results in both preclinical studies and clinical trials for certain cancer patients. However, there are still many questions that need to be answered, given the complexity of this pathway and the existence of its multiple feedback loops and interactions with other signaling pathways. In this paper, we will summarize recent advances in the understanding of the PI3K pathway role in human malignancies, with an emphasis on HNSCC, and discuss the clinical applications and future direction of this field. PMID- 22666250 TI - Budding of Enveloped Viruses: Interferon-Induced ISG15-Antivirus Mechanisms Targeting the Release Process. AB - Pathogenic strains of viruses that infect humans are encapsulated in membranes derived from the host cell in which they infect. After replication, these viruses are released by a budding process that requires cell/viral membrane scission. As such, this represents a natural target for innate immunity mechanisms to interdict enveloped virus spread and recent advances in this field will be the subject of this paper. PMID- 22666252 TI - Tissue regeneration in dentistry. PMID- 22666251 TI - Influence of different restorative techniques on the strength of endodontically treated weakened roots. AB - Objective. Comparing effect of different restoration techniques on fracture resistance of compromised roots. Methods. Crowns of 100 single-rooted teeth were sectioned and 10 roots were kept as negative control group (Group 1). Remaining roots were instrumented and divided into one and positive control group of 10 samples (Group 2) and 4 experimental groups of 20 samples each. Group 3: roots were obturated with gutta-percha; Group 4: roots were restored with gutta-percha, composite, and glass fiber post; Group 5: roots were obturated with Resilon; Group 6: Roots were restored with Resilon, composite, and glass fiber post. Roots were weakened before obturation in groups 2, 3, and 5 and after obturation in groups 4 and 6. Fracture strengths were measured using Dartec testing machine and fracture load was recorded in kilo-Newton. Statistical analysis was done using ANOVA and Tukeys test. Results. The fractures resistance of restored roots was significantly higher in groups 4, 5, and 6 than in Groups 2 and 3. There were no significant differences between groups 1, 4, 5, and 6. Conclusions. Restoration of weakened roots with Resilon or bonding an intermediate composite resin to coronal radicular dentin and to glass fiber post increased their fracture resistance. PMID- 22666253 TI - Innovative approaches to regenerate enamel and dentin. AB - The process of tooth mineralization and the role of molecular control of cellular behavior during embryonic tooth development have attracted much attention the last few years. The knowledge gained from the research in these fields has improved the general understanding about the formation of dental tissues and the entire tooth and set the basis for teeth regeneration. Tissue engineering using scaffold and cell aggregate methods has been considered to produce bioengineered dental tissues, while dental stem/progenitor cells, which can differentiate into dental cell lineages, have been also introduced into the field of tooth mineralization and regeneration. Some of the main strategies for making enamel, dentin, and complex tooth-like structures are presented in this paper. However, there are still significant barriers that obstruct such strategies to move into the regular clinic practice, and these should be overcome in order to have the regenerative dentistry as the important mean that can treat the consequences of tooth-related diseases. PMID- 22666249 TI - Interplay between HIV-1 and Host Genetic Variation: A Snapshot into Its Impact on AIDS and Therapy Response. AB - As of February 2012, 50 circulating recombinant forms (CRFs) have been reported for HIV-1 while one CRF for HIV-2. Also according to HIV sequence compendium 2011, the HIV sequence database is replete with 414,398 sequences. The fact that there are CRFs, which are an amalgamation of sequences derived from six or more subtypes (CRF27_cpx (cpx refers to complex) is a mosaic with sequences from 6 different subtypes besides an unclassified fragment), serves as a testimony to the continual divergent evolution of the virus with its approximate 1% per year rate of evolution, and this phenomena per se poses tremendous challenge for vaccine development against HIV/AIDS, a devastating disease that has killed 1.8 million patients in 2010. Here, we explore the interaction between HIV-1 and host genetic variation in the context of HIV/AIDS and antiretroviral therapy response. PMID- 22666254 TI - The use of buccal fat pad in the treatment of oral submucous fibrosis: a newer method. AB - Purpose of the study. This study was to evaluate the use of buccal fat pad as an interpositioning material in surgical management of oral sub mucous fibrosis. Materials and methods. A series of 8 cases with proven oral sub mucous fibrosis, with mouth opening less than 20 mm, involving the buccal mucosa were treated surgically in the Department of Oral and Maxillofacial Surgery, College of Dental Surgery, Saveetha University, Chennai. Pedicled buccal fat pad was used as an interpositioning material to cover the raw areas in the oral cavity after incision and release of fibrous bands. Results. In 8 patients, the range of pre operative mouth opening was 3-18 mm (mean 14 mm). As the result of the successful surgical procedure, the size of the intra operative mouth opening was ranged from 25-38 mm (mean 33.25 mm). The patients were discharged 5-7 days after the operation. The range of the mouth opening at this time was 25-36 mm (mean 30.63 mm). The results were evaluated using student's t test and found to be statistically significant. The pedicled grafts took up uneventfull. PMID- 22666255 TI - Fracture resistance of premolars restored by various types and placement techniques of resin composites. AB - To verify the fracture resistance of premolars with mesioocclusodistal preparations restored by different resin composites and placement techniques. Sixty premolars were randomly divided into two groups based on type of composite resin: Filtek P60 or Nulite F, and then each group was separated into three subgroups: bulk, centripetal, and fiber insert according to the type of placement method (n = 10). Single-bond adhesive system was used as composite bonding according to the manufacturer's instructions. Specimens were restored in Groups 1, 2, and 3 with Filtek P60 and in Groups 4, 5, and 6 with Nulite F. After being stored 24 hours at 37 degrees C, a 4 mm diameter steel sphere in a universal testing machine was applied on tooth buccal and lingual cusps at a cross-head speed of 5 mm/min until fracture occurred. Groups 3 and 6 showed higher fracture resistance than Groups 1, 2, 4, and 5. Among the placement techniques, the fiber insert method had a significant effect, but the type of composite was ineffective. The insertion technique in contrast to the type of material had a significant influence on the fracture resistance of premolar teeth. PMID- 22666257 TI - Early decrease in respiration and uncoupling event independent of cytochrome C release in PC12 cells undergoing apoptosis. AB - Cytochrome c is a key molecule in mitochondria-mediated apoptosis. It also plays a pivotal role in cell respiration. The switch between these two functions occurs at the moment of its release from mitochondria. This process is therefore extremely relevant for the fate of the cell. Since cytochrome c mediates respiration, we studied the changes in respiratory chain activity during the early stages of apoptosis in order to contribute to unravel the mechanisms of cytochrome c release. We found that, during staurosporine (STS)- induced apoptosis in PC12 cells, respiration is affected before the release of cytochrome c, as shown by a decrease in the endogenous uncoupled respiration and an uncoupling event, both occurring independently of cytochrome c release. The decline in the uncoupled respiration occurs also upon Bcl-2 overexpression (which inhibits cytochrome c release), while the uncoupling event is inhibited by Bcl-2. We also observed that the first stage of nuclear condensation during STS-induced apoptosis does not depend on the release of cytochrome c into the cytosol and is a reversibile event. These findings may contribute to understand the mechanisms affecting mitochondria during the early stages of apoptosis and priming them for the release of apoptogenic factors. PMID- 22666256 TI - Autophagy: more than a nonselective pathway. AB - Autophagy is a catabolic pathway conserved among eukaryotes that allows cells to rapidly eliminate large unwanted structures such as aberrant protein aggregates, superfluous or damaged organelles, and invading pathogens. The hallmark of this transport pathway is the sequestration of the cargoes that have to be degraded in the lysosomes by double-membrane vesicles called autophagosomes. The key actors mediating the biogenesis of these carriers are the autophagy-related genes (ATGs). For a long time, it was assumed that autophagy is a bulk process. Recent studies, however, have highlighted the capacity of this pathway to exclusively eliminate specific structures and thus better fulfil the catabolic necessities of the cell. We are just starting to unveil the regulation and mechanism of these selective types of autophagy, but what it is already clearly emerging is that structures targeted to destruction are accurately enwrapped by autophagosomes through the action of specific receptors and adaptors. In this paper, we will briefly discuss the impact that the selective types of autophagy have had on our understanding of autophagy. PMID- 22666259 TI - The Association between Myocardial Iron Load and Ventricular Repolarization Parameters in Asymptomatic Beta-Thalassemia Patients. AB - Previous studies have demonstrated impaired ventricular repolarization in patients with beta-TM. However, the effect of iron overload with cardiac T2* magnetic resonance imaging (MRI) on cardiac repolarization remains unclear yet. We aimed to examine relationship between repolarization parameters and iron loading using cardiac T2* MRI in asymptomatic beta-TM patients. Twenty-two beta TM patients and 22 age- and gender-matched healthy controls were enrolled to the study. From the 12-lead surface electrocardiography, regional and transmyocardial repolarization parameters were evaluated manually by two experienced cardiologists. All patients were also undergone MRI for cardiac T2* evaluation. Cardiac T2* score <20 msec was considered as iron overload status. Of the QT parameters, QT duration, corrected QT interval, and QT peak duration were significantly longer in the beta-TM group compared to the healthy controls. T(p) T(e) and T(p) - T(e) dispersions were also significantly prolonged in beta-TM group compared to healthy controls. (T(p) - T(e))/QT was similar between groups. There was no correlation between repolarization parameters and cardiac T2* MRI values. In conclusion, although repolarization parameters were prolonged in asymptomatic beta-TM patients compared with control, we could not find any relation between ECG findings and cardiac iron load. PMID- 22666258 TI - Oxidative stress, tumor microenvironment, and metabolic reprogramming: a diabolic liaison. AB - Conversely to normal cells, where deregulated oxidative stress drives the activation of death pathways, malignant cells exploit oxidative milieu for its advantage. Cancer cells are located in a very complex microenvironment together with stromal components that participate to enhance oxidative stress to promote tumor progression. Indeed, convincing experimental and clinical evidence underline the key role of oxidative stress in several tumor aspects thus affecting several characteristics of cancer cells. Oxidants influence the DNA mutational potential, intracellular signaling pathways controlling cell proliferation and survival and cell motility and invasiveness as well as control the reactivity of stromal components that is fundamental for cancer development and dissemination, inflammation, tissue repair, and de novo angiogenesis. This paper is focused on the role of oxidant species in the acquisition of two mandatory features for aggressive neoplastic cells, recently defined by Hanahan and Weinberg as new "hallmarks of cancer": tumor microenvironment and metabolic reprogramming of cancer cells. PMID- 22666260 TI - Immunosuppression Adversely Affects TST but Not IGRAs in Patients with Psoriasis or Inflammatory Musculoskeletal Diseases. AB - The performance of the interferon gamma release assays (IGRAs) and tuberculin skin test (TST) was reviewed retrospectively in patients with psoriasis, inflammatory musculoskeletal diseases, or miscellaneous inflammatory conditions. The study was carried out over a 22-month period using 109 records of patients with psoriasis (n = 21), musculoskeletal disease (n = 74), or other inflammatory conditions (n = 14). Forty-four (48%) of 109 patients were on immunosuppressive therapy and 38/109 (35%) on systemic glucocorticoid therapy. The agreement between the IGRAs was substantial (kappa = 0.71) whilst that between the IGRAs and TST was low (kappa = 0.32). Logistic regression models revealed that IGRAs associated with risk factors for latent tuberculosis infection better than TST. TST was influenced by age, BCG vaccination, sex, and glucocorticoid therapy. We found that IGRAs performed equally well with low level of indeterminate results (1-2%). IGRAs were superior to TST because the latter was influenced by BCG vaccination status and immunosuppressive therapy. PMID- 22666261 TI - The Association of IL-12b Polymorphisms with Systemic Lupus Erythematosus in Chinese Han Population. AB - Background. Systemic lupus erythematosus (SLE) is a complex immune disease. The genetic variation in the IL-12b gene was found to associate with SLE in Caucasian population. In this study, we examined this association in Chinese Han population by a recently developed method, unlabeled probe-based high resolution melting analysis. Methods. A total of 297 SLE patients and 351 controls were recruited. Unlabeled probe-based high resolution melting analysis (HRMA) was used in genotyping. Results. Statistically significant differences were observed in both genotype and allele frequencies for rs6887695 in the SLE patients as compared with the controls. Minor allele (C) of rs6887695 (P = 0.031, OR 0.78, [95% CI 0.63-0.98]) was found to be protective against SLE. The association of SNP rs6887695 with the diagnostic criteria of SLE was also examined. Minor allele (C) exerts protective effect on the incidence of arthritis (P = 0.013, OR = 0.65, 95% CI = 0.47-0.92) and abnormalities of antinuclear antibody (P = 0.022, OR = 0.68, 95% CI = 0.49-0.95). IL-12b SNPs were irrelevant to other diagnostic criteria of SLE. Summary. Polymorphisms of rs6887695 in IL-12b gene were associated with disease risk, as well as arthritis and antinuclear antibody synthesis, of systemic lupus erythematosus in Chinese population. PMID- 22666262 TI - Causal ACTH-Depot Therapy during Pregnancies following Infertility Treatment. AB - The aim of this paper was to confirm the efficacy of adrenocorticotropin depot (ACTH-depot) therapy in pregnancies with threatened miscarriage and preterm delivery through the desired stimulation of the adrenal glands controlled by the rest of organism. The activity of hypothalamic-pituitary-adrenal axis plays a key role in pregnancy. Such naturally stimulated endogenous corticosteroid hormones are free from unwanted side effects of their synthetics analogs. Low level of maternal blood ACTH and insufficient increase of induced by hypothalamic hormones oxytocinases (cystine-beta-aminopeptidases) were indication to ACTH-depot therapy (0.5 mg/week) in our consecutive prospective studies. Contrary to antenatal use of synthetic corticosteroids, there are no temporal limits of this therapy, which has to be more often recommended into clinical prevention of fetal morbidity, treatment of premature delivery, and finally elimination of the newborn's mortality caused by the neuroendocrinological gestoses. PMID- 22666263 TI - Familial aggregation of urinary tract and bone tumors: searching for a syndrome. AB - Positive family anamnesis is an important risk factor for cancer, and therefore further investigations need to be done if familial aggregation of cancer is observed. Due to a rare combination of urinary tract and bone tumors occurring in the family presented herein we hypothesized a hereditary predisposition and thus, Li-Fraumeni syndrome was considered to be the most likely differential diagnosis. To confirm Li-Fraumeni syndrome, we set out to investigate this case by analyzing the tumor suppressor gene p53. However, taking into account all the diagnostic results obtained, Li-Fraumeni syndrome could not be confirmed, but there is still uncertainty regarding a definitive diagnosis. PMID- 22666264 TI - Treatment of endovascular coil and stent migration using the merci retriever: report of three cases. AB - Background. Coil and stent migration is a potentially catastrophic complication in endovascular neurosurgery, which may lead to cerebral thromboembolism. Techniques for removing migrated coil and stent are not well established. Methods and Results. We present three cases in which coil or stent migration occurred during endovascular embolization of a cerebral aneurysm. The Merci Retrievers were used successfully in all cases to remove the displaced foreign bodies. Technical details are described. Conclusion. The Merci Retriever device can be utilized successfully for removal of migrated coils and stents in endovascular neurosurgery. PMID- 22666265 TI - Salter-Harris Type III and Type IV Combined Fracture of the Distal Femoral Epiphysis: A Case Report. AB - Distal femoral physeal fractures are not common but have a high rate of complications. They generally follow one of the patterns described in the Salter Harris classification. We present a case of combination of Salter-Harris type III and type IV injury. Our case was a 15-year-old boy who had a motor vehicle accident. There was swelling, ecchymosis, severe pain, and valgus deformity, because of medial proximal fracture fragment, on the left knee. We deemed that Salter-Harris type III and type IV combination fracture in our case has not been previously reported. We prepared this paper in consideration of its contribution to the literature. PMID- 22666266 TI - Osteochondral avulsion fracture of the femoral origin of the anterior cruciate ligament in an 11-year-old child. AB - Although tibial end avulsions of the anterior cruciate ligament are relatively common in clinical practice, avulsions of the femoral end of this ligament are by comparison rare. We present the case of an 11-year-old boy with a bony avulsion injury, which was presumed to have arisen from the tibial insertion of the anterior cruciate ligament but turned out instead to be an osteochondral avulsion fracture of the femoral origin. This unexpected finding that was not detected during preoperative workup resulted in the first attempt at surgical fixation being aborted. The need for a second planned definitive fixation procedure emphasises the importance of combining a thorough history and examination in association with appropriate imaging in the patient workup. The patient's definitive operative treatment and outcome are described. Although rare, surgeons (and emergency room doctors) treating such patients should include femoral end avulsion injuries of the anterior cruciate ligament in the differential diagnosis of a child presenting with an acute haemarthrosis of the knee. Furthermore, once diagnosed, early onward referral to an experienced knee surgeon is advocated. PMID- 22666267 TI - Phytocontact Dermatitis due to Mustard Seed Mimicking Burn Injury: Report of a Case. AB - Mustard seeds have been used in traditional folk medicine as a stimulant, diuretic, and purgative and to treat a variety of ailments including peritonitis and neuralgia. Mustards are still used today in mustard plasters to treat rheumatism, arthritis, chest congestion, aching back, and sore muscles. To make a mustard plaster, mix equal parts of flour and powdered mustard and spread it as a paste on a doubled piece of soft cloth. Apply mustard plaster to the affected area for a maximum of 15 minutes. Prolonged application can result in burns to the skin and nerve damage. Skin lesions occur within hours after exposure, and there is no significant therapy procedure. This case report is about a patient with second-degree burn, occurred when a mixture including mustard seed was exposed to her skin in the pain therapy of the osteoarthritis in her left knee. There are no studies analyzing treatment of skin burns induced by mustard seed in the literature. While in this type of burns our experience is limited, we think that conservative approach should be first choice of treatment. PMID- 22666268 TI - A rare case of myeloid sarcoma presenting as an anorectal ulcer. AB - Myeloid Sarcoma is a rare tumor composed of myeloblasts occurring at an extramedullary site like bones, or various soft tissues. Myeloid sarcoma may involve the gastrointestinal tract very rarely either solitarily, or occurring simultaneously with acute myeloid leukemia. Its diagnosis is challenging and needs biopsy and immunohistochemical staining. We are describing a case of myeloid sarcoma which presented as a painful anal ulcer mimicking an atypical fissure. Its appearance resembled crohn's disease on sigmoidoscopy. A biopsy of the ulcer along with histochemical staining led to the diagnosis of myeloid sarcoma. Our case demonstrates the need for aggressive evaluation of any common gastrointestinal complaint with an atypical presentation. PMID- 22666270 TI - Stem cells in large animal models of retinal and neurological disease. PMID- 22666269 TI - Extrafollicular dermal melanocyte stem cells and melanoma. AB - Recent studies suggest that extrafollicular dermal melanocyte stem cells (MSCs) persist after birth in the superficial nerve sheath of peripheral nerves and give rise to migratory melanocyte precursors when replacements for epidermal melanocytes are needed on the basal epidermal layer of the skin. If a damaged MSC or melanocyte precursor can be shown to be the primary origin of melanoma, targeted identification and eradication of it by antibody-based therapies will be the best method to treat melanoma and a very effective way to prevent its recurrence. Transcription factors and signaling pathways involved in MSC self renewal, expansion and differentiation are reviewed. A model is presented to show how the detrimental effects of long-term UVA/UVB radiation on DNA and repair mechanisms in MSCs convert them to melanoma stem cells. Zebrafish have many advantages for investigating the role of MSCs in the development of melanoma. The signaling pathways regulating the development of MSCs in zebrafish are very similar to those found in humans and mice. The ability to easily manipulate the MSC population makes zebrafish an excellent model for studying how damage to MSCs may lead to melanoma. PMID- 22666271 TI - Mesenchymal stem cells isolated from adipose and other tissues: basic biological properties and clinical applications. AB - Mesenchymal stem cells (MSCs) are adult stem cells that were initially isolated from bone marrow. However, subsequent research has shown that other adult tissues also contain MSCs. MSCs originate from mesenchyme, which is embryonic tissue derived from the mesoderm. These cells actively proliferate, giving rise to new cells in some tissues, but remain quiescent in others. MSCs are capable of differentiating into multiple cell types including adipocytes, chondrocytes, osteocytes, and cardiomyocytes. Isolation and induction of these cells could provide a new therapeutic tool for replacing damaged or lost adult tissues. However, the biological properties and use of stem cells in a clinical setting must be well established before significant clinical benefits are obtained. This paper summarizes data on the biological properties of MSCs and discusses current and potential clinical applications. PMID- 22666273 TI - Survey of water bugs in bankim, a new buruli ulcer endemic area in cameroon. AB - Buruli ulcer is a debitliating human skin disease with an unknown transmission mode although epidemiological data link it with swampy areas. Data available suggest that aquatic insects play a role in the dissemination and/or transmission of this disease. However, their biodiversity and biology remain poorly documented. We conducted an entomological survey in Bankim, Cameroon, an area recently described as endemic for Buruli ulcer in order to identify the commonly occurring aquatic bugs and document their relative abundance, diversity, and spatial distribution. Collection of aquatic bugs was realized over a period of one month by daily direct capture in different aquatic environments (streams, ponds, and rivers) and through light traps at night. Globally, the data obtained showed the presence of five families (Belostomatidae, Naucoridae, Nepidae, Notonectidae, and Gerridae), their abundance, distribution and diversity varying according to the type of aquatic environments and light attraction. PMID- 22666274 TI - Neonatal respiratory care. PMID- 22666272 TI - Markers for characterization of bone marrow multipotential stromal cells. AB - Given the observed efficacy of culture-expanded multipotential stromal cells, also termed mesenchymal stem cells (MSCs), in the treatment of graft-versus host and cardiac disease, it remains surprising that purity and potency characterization of manufactured cell batches remains rather basic. In this paper, we will initially discuss surface and molecular markers that were proposed to serve as the indicators of the MSC potency, in terms of their proliferative potential or the ability to differentiate into desired lineages. The second part of this paper will be dedicated to a critical discussion of surface markers of uncultured (i.e., native) bone marrow (BM) MSCs. Although no formal consensus has yet been reached on which markers may be best suited for prospective BM MSC isolation, markers that cross-react with MSCs of animal models (such as CD271 and W8-B2/MSCA-1) may have the strongest translational value. Whereas small animal models are needed to discover the in vivo function on these markers, large animal models are required for safety and efficacy testing of isolated MSCs, particularly in the field of bone and cartilage tissue engineering. PMID- 22666275 TI - Postnatal Growth Patterns in a Chilean Cohort: The Role of SES and Family Environment. AB - Objective. This study examined how family environmental characteristics served as mediators in the relationship between socioeconomic conditions and infant growth in a cohort of Chilean infants. Methods. We studied 999 infants, born between 1991 and 1996, from a longitudinal cohort which began as an iron deficiency anemia preventive trial. SES (Graffar Index), the Life Experiences Survey, and the Home Observation for Measurement of the Environment (HOME) were assessed in infancy. Using path analysis, we assessed the relationships between the social factors, home environment, and infant growth. Results. During the first year, weight and length gain averaged 540 grams/month and 6.5 cm/month, respectively. In the path analysis model for weight gain, higher SES and a better physical environment were positively related to higher maternal warmth, which in turn was associated with higher average weight gain. Higher SES was directly related to higher average length gain. Conclusions. In our cohort, a direct relationship between SES and length gain developed during infancy. Higher SES was indirectly related to infant weight gain through the home environment and maternal warmth. As the fastest growing infants are at risk for later obesity, new strategies are needed to encourage optimal rather than maximal growth. PMID- 22666276 TI - Proline rich motifs as drug targets in immune mediated disorders. AB - The current version of the human immunome network consists of nearly 1400 interactions involving approximately 600 proteins. Intermolecular interactions mediated by proline-rich motifs (PRMs) are observed in many facets of the immune response. The proline-rich regions are known to preferentially adopt a polyproline type II helical conformation, an extended structure that facilitates transient intermolecular interactions such as signal transduction, antigen recognition, cell-cell communication and cytoskeletal organization. The propensity of both the side chain and the backbone carbonyls of the polyproline type II helix to participate in the interface interaction makes it an excellent recognition motif. An advantage of such distinct chemical features is that the interactions can be discriminatory even in the absence of high affinities. Indeed, the immune response is mediated by well-orchestrated low-affinity short duration intermolecular interactions. The proline-rich regions are predominantly localized in the solvent-exposed regions such as the loops, intrinsically disordered regions, or between domains that constitute the intermolecular interface. Peptide mimics of the PRM have been suggested as potential antagonists of intermolecular interactions. In this paper, we discuss novel PRM-mediated interactions in the human immunome that potentially serve as attractive targets for immunomodulation and drug development for inflammatory and autoimmune pathologies. PMID- 22666277 TI - Trends in roll-your-own smoking: findings from the ITC Four-Country Survey (2002 2008). AB - OBJECTIVE: To establish the trends in prevalence, and correlates, of roll-your own (RYO) use in Canada, USA, UK and Australia, 2002-2008. METHODS: Participants were 19,456 cigarette smokers interviewed during the longitudinal International Tobacco Control (ITC) Four-Country Survey in Canada, USA, UK, and Australia. RESULTS: "Predominant" RYO use (i.e., >50% of cigarettes smoked) increased significantly in the UK and USA as a proportion of all cigarette use (both P < .001) and in all countries as a proportion of any RYO use (all P < .010). Younger, financially stressed smokers are disproportionately contributing to "some" use (i.e., <=50% of cigarettes smoked). Relative cost was the major reason given for using RYO, and predominant RYO use is consistently and significantly associated with low income. CONCLUSIONS: RYO market trends reflect the price advantages accruing to RYO (a product of favourable taxation regimes in some jurisdictions reinforced by the enhanced control over the amount of tobacco used), especially following the impact of the Global Financial Crisis; the availability of competing low-cost alternatives to RYO; accessibility of duty free RYO tobacco; and tobacco industry niche marketing strategies. If policy makers want to ensure that the RYO option does not inhibit the fight to end the tobacco epidemic, especially amongst the disadvantaged, they need to reduce the price advantage, target additional health messages at (young) RYO users, and challenge niche marketing of RYO by the industry. PMID- 22666278 TI - The relationship between insufficient sleep and self-rated health in a nationally representative sample. AB - Reduced sleep has been found to be associated with increased risk of diabetes mellitus, hypertension, cardiovascular disease (CVD), and mortality. Self-rated health (SRH) has been shown to be a predictor of CVD and mortality. However, study of the association between insufficient sleep and SRH is limited. We examined participants >18 years of age (n = 377, 160) from a representative, cross-sectional survey (2008 BRFSS). Self-reported insufficient sleep in the previous 30 days was categorized into six groups. The outcome was poor SRH. We calculated odds ratios ((OR) (95% confidence interval (CI)) of increasing categories of insufficient rest/sleep, taking zero days of insufficient sleep as the referent category. We found a positive association between increasing categories of insufficient sleep and poor SRH, independent of relevant covariates. In the multivariable-adjusted model, compared to 0 days insufficient sleep, the OR (95% CI) of poor SRH was 1.03 (0.97-1.10) for 1-6 days, 1.45 (1.34 1.57) for 7-13 days, 2.12 (1.97-2.27) for 14-20 days, 2.32 (2.09-2.58) for 21-29 days, and and 2.71 (2.53-2.90) for 30 days of insufficient sleep in the prior 30 days (P-trend <0.0001). In a nationally representative sample, increasing categories of insufficient sleep were associated with poor SRH. PMID- 22666279 TI - Patterns of tobacco use and dual use in US young adults: the missing link between youth prevention and adult cessation. AB - Few studies address the developmental transition from youth tobacco use uptake to regular adulthood use, especially for noncigarette tobacco products. The current study uses online panel data from the Legacy Young Adult Cohort Study to describe the prevalence of cigarette, other tobacco product, and dual use in a nationally representative sample of young adults aged 18-34 (N = 4,201). Of the 23% of young adults who were current tobacco users, 30% reported dual use. Ever use, first product used, and current use were highest for cigarettes, cigars, little cigars, and hookah. Thirty-two percent of ever tobacco users reported tobacco product initiation after the age of 18 and 39% of regular users reported progressing to regular use during young adulthood. This study highlights the need for improved monitoring of polytobacco use across the life course and developing tailored efforts for young adults to prevent progression and further reduce overall population prevalence. PMID- 22666280 TI - Concurrent use of cigarettes and smokeless tobacco among US males and females. AB - BACKGROUND: The current study describes concurrent use of cigarettes and smokeless tobacco (CiST) among males and females and evaluates factors associated with CiST use. METHODS: Cross-sectional data were drawn from the 2010 Behavioral Risk Factor Surveillance System (BRFSS). Weighted stratified analyses were performed to find associations between CiST use and sociodemographic factors by gender. CiST users were compared to three different tobacco use groups: nonusers, exclusive smokers, and exclusive ST users. RESULTS: Younger age and heavy alcohol consumption were consistently associated with increased odds of CiST use among both males and females, and regardless of comparison group. Among males, education was inversely related to CiST use, and these findings were consistent in all three comparisons. Among women, those unable to work or out of work were more likely to be CiST users, which was consistent across comparisons. American Indian females had higher odds of CiST use than White females when nontobacco users or smokers were the comparison group. CONCLUSION: This study identified sociodemographic characteristics associated with CiST use, and differences in these associations among women and men. Additionally, this study highlights the need to carefully consider what comparison groups should be used to examine factors associated with CiST use. PMID- 22666282 TI - Herpes simplex virus-2 glycoprotein interaction with HVEM influences virus specific recall cellular responses at the mucosa. AB - Infection of susceptible cells by herpes simplex virus (HSV) requires the interaction of the HSV gD glycoprotein with one of two principal entry receptors, herpes virus entry mediator (HVEM) or nectins. HVEM naturally functions in immune signaling, and the gD-HVEM interaction alters innate signaling early after mucosal infection. We investigated whether the gD-HVEM interaction during priming changes lymphocyte recall responses in the murine intravaginal model. Mice were primed with attenuated HSV-2 expressing wild-type gD or mutant gD unable to engage HVEM and challenged 32 days later with virulent HSV-2 expressing wild-type gD. HSV-specific CD8(+) T cells were decreased at the genital mucosa during the recall response after priming with virus unable to engage HVEM but did not differ in draining lymph nodes. CD4(+) T cells, which are critical for entry of HSV specific CD8(+) T cells into mucosa in acute infection, did not differ between the two groups in either tissue. An inverse association between Foxp3(+) CD4(+) regulatory T cells and CD8(+) infiltration into the mucosa was not statistically significant. CXCR3 surface expression was not significantly different among different lymphocyte subsets. We conclude that engagement of HVEM during the acute phase of HSV infection influences the antiviral CD8(+) recall response by an unexplained mechanism. PMID- 22666281 TI - Cellular and humoral mechanisms involved in the control of tuberculosis. AB - Mycobacterium tuberculosis (Mtb) infection is a major international public health problem. One-third of the world's population is thought to have latent tuberculosis, a condition where individuals are infected by the intracellular bacteria without active disease but are at risk for reactivation, if their immune system fails. Here, we discuss the role of nonspecific inflammatory responses mediated by cytokines and chemokines induced by interaction of innate receptors expressed in macrophages and dendritic cells (DCs). We also review current information regarding the importance of several cytokines including IL-17/IL-23 in the development of protective cellular and antibody-mediated protective responses against Mtb and their influence in containment of the infection. Finally, in this paper, emphasis is placed on the mechanisms of failure of Mtb control, including the immune dysregulation induced by the treatment with biological drugs in different autoimmune diseases. Further functional studies, focused on the mechanisms involved in the early host-Mtb interactions and the interplay between host innate and acquired immunity against Mtb, may be helpful to improve the understanding of protective responses in the lung and in the development of novel therapeutic and prophylactic tools in TB. PMID- 22666283 TI - Sorafenib prevents escape from host immunity in liver cirrhosis patients with advanced hepatocellular carcinoma. AB - PURPOSE: It has been reported that Th2 cytokines downregulate antitumor immunity, while activation of type T cells promotes antitumor immunity. The aim of this paper was to evaluate host immunity in liver cirrhosis (LC) patients with advanced hepatocellular carcinoma (aHCC) receiving sorafenib therapy. METHODS: Forty-five adult Japanese LC patients received sorafenib for aHCC between 2009 and 2011 at our hospital. Sorafenib was administered at a dose of 200-800 mg/day for 4 weeks. Blood samples were collected before and after treatment. RESULTS: Eleven patients were treated with sorafenib at 200 mg/day (200 group), 27 patients received sorafenib at 400 mg/day (400 group), and 7 patients were given sorafenib at 800 mg/day (800 group). There was no significant change in the percentage of Th1 cells after treatment in any group. However, the percentages of Th2 cells and regulatory T cells were significantly decreased after treatment in the 400 group and 800 group compared with before treatment, although there was no significant change after treatment in the 200 group. CONCLUSIONS: These results indicate that treatment with sorafenib might induce Th1 dominance and prevent the escape of tumor cells from the host immune system in LC patients with aHCC. PMID- 22666285 TI - Heterogeneity of skin surface oxygen level of wrist in relation to acupuncture point. AB - The distribution of partial oxygen pressure (pO(2)) is analyzed for the anterior aspect of the left wrist with an amperometric oxygen microsensor composed of a small planar Pt disk-sensing area (diameter = 25 MUm). The pO(2) levels vary depending on the measurement location over the wrist skin, and they are systematically monitored in the analysis for both one-dimensional single line (along the wrist transverse crease) and two-dimensional square area of the wrist region. Relatively higher pO(2) values are observed at certain area in close proximity to the position of acupuncture points with statistical significance, indicating strong relationship between oxygen and acupuncture point. The used oxygen microsensor is sensitive enough to detect the pO(2) variation depending on the location. This study may provide information helpful to understand possible physiological roles of the acupuncture points. PMID- 22666286 TI - Sino-European Transcontinental Basic and Clinical High-Tech Acupuncture Studies Part 4: "Fire of Life" Analysis of Heart Rate Variability during Acupuncture in Clinical Studies. AB - This fourth part of a series of Sino-European high-tech acupuncture studies describes the first clinical transcontinental teleacupuncture measurements in two patients (cervical spine syndrome and tachycardia; both 27 years old) from the Beijing Hospital of Traditional Chinese Medicine affiliated to Capital Medical University, China. The electrocardiographic data were transferred to the Stronach Research Unit for Complementary and Integrative Laser Medicine and the TCM Research Center in Graz via conventional internet connections. Data analysis was performed in Graz using a new "Fire of Life" heart rate variability analysis. Analysis was performed without any technical problems in both subjects. Heart rate decreased significantly during acupuncture in the two patients from Beijing. At the same time, total HRV increased during acupuncture. The different influences of HRV (respiratory sinus arrhythmia, blood pressure waves, etc.) could be clearly documented using the new "Fire of Life" analysis. PMID- 22666284 TI - Characteristics of suppressor macrophages induced by mycobacterial and protozoal infections in relation to alternatively activated M2 macrophages. AB - In the advanced stages of mycobacterial infections, host immune systems tend to change from a Th1-type to Th2-type immune response, resulting in the abrogation of Th1 cell- and macrophage-mediated antimicrobial host protective immunity. Notably, this type of immune conversion is occasionally associated with the generation of certain types of suppressor macrophage populations. During the course of Mycobacterium tuberculosis (MTB) and Mycobacterium avium-intracellulare complex (MAC) infections, the generation of macrophages which possess strong suppressor activity against host T- and B-cell functions is frequently encountered. This paper describes the immunological properties of M1- and M2-type macrophages generated in tumor-bearing animals and those generated in hosts with certain microbial infections. In addition, this paper highlights the immunological and molecular biological characteristics of suppressor macrophages generated in hosts with mycobacterial infections, especially MAC infection. PMID- 22666287 TI - Molecular Mechanism of Isocupressic Acid Supresses MA-10 Cell Steroidogenesis. AB - Consumption of ponderosa pine needles causes late-term abortions in cattle and is a serious poisonous plant problem in foothill and mountain rangelands. Isocupressic acid (IA) is the component of pine needles responsible for the abortifacient effect, its abortifacient effect may be due to inhibition of steroidogenesis. To investigate the more detail molecular mechanism, we used MA 10 cell, which is wild used to investigate molecular mechanism of steroidogenesis, to characterize the molecular mechanisms underlying the actions of IA in more detail. In this report, we focus on the function of IA on important steroidogenic genes, including steroidogenic acute regulatory protein (StAR), cytochrome P450 cholesterol side-chain cleavage (P450scc), and 3beta hydroxysteroid dehydrogenase (3beta-HSD). We found that IA does not affect enzyme activities of these genes but inhibits transcription of P450scc and translation of StAR and P450scc through attenuating cAMP-PKA signaling. Thus, steroid productions of cells were suppressed. PMID- 22666288 TI - A chan dietary intervention enhances executive functions and anterior cingulate activity in autism spectrum disorders: a randomized controlled trial. AB - Executive dysfunctions have been found to be related to repetitive/disinhibited behaviors and social deficits in autism spectrum disorders (ASDs). This study aims to investigate the potential effect of a Shaolin-medicine-based dietary modification on improving executive functions and behavioral symptoms of ASD and exploring the possible underlying neurophysiological mechanisms. Twenty-four children with ASD were randomly assigned into the experimental (receiving dietary modification for one month) and the control (no modification) groups. Each child was assessed on his/her executive functions, behavioral problems based on parental ratings, and event-related electroencephalography (EEG) activity during a response-monitoring task before and after the one month. The experimental group demonstrated significantly improved mental flexibility and inhibitory control after the diet modification, which continued to have a large effect size within the low-functioning subgroup. Such improvements coincided with positive evaluations by their parents on social communication abilities and flexible inhibitory control of daily behaviors and significantly enhanced event-related EEG activity at the rostral and subgenual anterior cingulate cortex. In contrast, the control group did not show any significant improvements. These positive outcomes of a one-month dietary modification on children with ASD have implicated its potential clinical applicability for patients with executive function deficits. PMID- 22666289 TI - Analgesic and Anti-Inflammatory Activities of Methanol Extract of Ficus pumila L. in Mice. AB - This study investigated possible analgesic and anti-inflammatory mechanisms of the methanol extract of Ficus pumila (FP(MeOH)). Analgesic effects were evaluated in two models including acetic acid-induced writhing response and formalin induced paw licking. The results showed FP(MeOH) decreased writhing response in the acetic acid assay and licking time in the formalin test. The anti inflammatory effect was evaluated by lambda-carrageenan-induced mouse paw edema and histopathological analyses. FP(MeOH) significantly decreased the volume of paw edema induced by lambda-carrageenan. Histopathologically, FP(MeOH) abated the level of tissue destruction and swelling of the edema paws. This study indicated anti-inflammatory mechanism of FP(MeOH) may be due to declined levels of NO and MDA in the edema paw through increasing the activities of SOD, GPx, and GRd in the liver. Additionally, FP(MeOH) also decreased the level of inflammatory mediators such as IL-1beta, TNF-alpha, and COX-2. HPLC fingerprint was established and the contents of three active ingredients, rutin, luteolin, and apigenin, were quantitatively determined. This study provided evidence for the classical treatment of Ficus pumila in inflammatory diseases. PMID- 22666290 TI - Neuroprotective Activity of Sibjeondaebo-tang on Abeta Peptide-Induced Damages. AB - Background. Sibjeondaebo-tang (SJDBT) has been used to treat diverse disorders including neuropsychiatric disabilities in traditional Korean medicine. Objective. The present study aims to investigate the potential effects of SJDBT on neuroprotection against Abeta peptide-induced damage using in vitro culture and in vivo rat brain systems. Materials and Methods. PC12 cell viability was analyzed by MTT assay, and neurite arborizations and caspase 3 protein signals in cultured PC12 cells and in vivo cortical neurons were analyzed by immunofluorescence staining. Phospho-Erk1/2 protein was analyzed by immunofluorescence staining and western blot analysis. Results. In PC12 cells, atrophied cell body and reduced neurite extension by Abeta treatment were recovered by SJDBT treatment. Caspase 3 protein signals were increased in Abeta treated PC12 cells, but SJDBT treatment decreased apoptotic cell death. Caspase 3 activation in cortical neurons, which was induced similarly by Abeta treatment, was reduced by SJDBT treatment. Furthermore, phospho-Erk1/2 protein levels, which had been decreased by Abeta treatment, were elevated in the cortical neurons by SJDBT treatment. Conclusion. These data show that SJDBT may play a role in protecting from damages induced by Abeta in neuronal tissue and further suggest that SJDBT can be explored as the potential therapeutic target for AD treatments in human. PMID- 22666291 TI - A comparison of wound healing rate following treatment with aftamed and chlorine dioxide gels in streptozotocin-induced diabetic rats. AB - Background and Purpose. This study aimed to evaluate the wound healing activities of Aftamed and chlorine dioxide gels in streptozotocin-induced diabetic rats. Experimental Approach. Forty-eight Sprague Dawley rats were chosen for this study, divided into 4 groups. Diabetes was induced. Two-centimeter-diameter full thickness skin excision wounds were created. Animals were topically treated twice daily. Groups 1, the diabetic control group, were treated with 0.2 mL of sterile distilled water. Group 2 served as a reference standard were treated with 0.2 mL of Intrasite gel. Groups 3 and 4 were treated with 0.2 mL of Aftamed and 0.2 mL of chlorine dioxide gels respectively. Granulation tissue was excised on the 10th day and processed for histological and biochemical analysis. The glutathione peroxidase ,superoxide dismutase activities and the malondialdehyde (MDA) levels were determined. Results. Aftamed-treated wounds exhibited significant increases in hydroxyproline, cellular proliferation, the number of blood vessels, and the level of collagen synthesis. Aftamed induced an increase in the free radical scavenging enzyme activity and significantly reduced the lipid peroxidation levels in the wounds as measured by the reduction in the MDA level. Conclusions. This study showed that Aftamed gel is able to significantly accelerate the process of wound healing in diabetic rats. PMID- 22666292 TI - The effects of scraping therapy on local temperature and blood perfusion volume in healthy subjects. AB - Objective. We aim to study the therapeutic effects of scraping by investigating the changes of temperature and local blood perfusion volume in healthy subjects after scraping stimulation, and to explore the mechanism of scraping stimulation from the points of microcirculation and energy metabolism. Methods. Twenty-three health subjects were included in this study. Local blood perfusion volume and body surface temperature was detected at 5 min before scraping stimulation, 0, 15, 30, 60 and 90 min after scraping using Laser Doppler imager and infrared thermograph. Results. Significant increase was noted in the blood perfusion volume in the scraping area within 90 minutes compared to the baseline level and non-scraping area (P < 0.001). Compared with non-scraping area, an increase of body temperature with an average of 1 degrees C was observed after scraping stimulation (P < 0.01). Conclusion. Scraping can significantly improve the blood perfusion volume and increase the temperature in the scraping area, promoting the local blood circulation and energy metabolism. PMID- 22666293 TI - Antiviral Ability of Kalanchoe gracilis Leaf Extract against Enterovirus 71 and Coxsackievirus A16. AB - Pandemic infection or reemergence of Enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) occurs in tropical and subtropical regions, being associated with hand foot-and-mouth disease, herpangina, aseptic meningitis, brain stem encephalitis, pulmonary edema, and paralysis. However, effective therapeutic drugs against EV71 and CVA16 are rare. Kalanchoe gracilis (L.) DC is used for the treatment of injuries, pain, and inflammation. This study investigated antiviral effects of K. gracilis leaf extract on EV71 and CVA16 replications. HPLC analysis with a C-18 reverse phase column showed fingerprint profiles of K. gracilis leaf extract had 15 chromatographic peaks. UV/vis absorption spectra revealed peaks 5, 12, and 15 as ferulic acid, quercetin, and kaempferol, respectively. K. gracilis leaf extract showed little cytotoxicity, but exhibited concentration-dependent antiviral activities including cytopathic effect, plaque, and virus yield reductions. K. gracilis leaf extract was shown to be more potent in antiviral activity than ferulic acid, quercetin, and kaempferol, significantly inhibiting in vitro replication of EV71 (IC(50) = 35.88 MUg/mL) and CVA16 (IC(50) = 42.91 MUg/mL). Moreover, K. gracilis leaf extract is a safe antienteroviral agent with the inactivation of viral 2A protease and reduction of IL-6 and RANTES expressions. PMID- 22666294 TI - Neutralisation of Local Haemorrhage Induced by the Saw-Scaled Viper Echis carinatus sochureki Venom Using Ethanolic Extract of Hibiscus aethiopicus L. AB - The objective of the study is to investigate the anti-snake venom activities of a local plant, Hibiscus aethiopicus L. The H. aethiopicus was dried and extracted with ethanol. Different assays were performed according to standard techniques, to evaluate the plant's acute toxicity and its antivenom activities. The results of evaluating the systemic acute toxicity of the H. aethiopicus extract using "oral and intra-peritoneal" route were normal even at the highest dose (24 g/kg) tested. All guinea pigs (n = 3) when treated with venoms E. c. sochureki (75 MUg) alone induced acute skin haemorrhage. In contrast, all guinea pigs (n = 18) treated with both venom and the plant extract at a concentration between 500 and 1000 mg/kg showed no signs of haemorrhage. Moreover, all guinea pigs (n = 18) treated with venom and the plant extract below 400 mg/kg showed acute skin haemorrhage. All guinea pigs treated with venom E. c. sochureki (75 MUg) alone induced acute skin haemorrhage after both 24 and 32 hours. In contrast, all guinea pigs treated with both venom and the plant extract (administered independently) at concentrations between 500 and 1000 mg/kg showed no signs of haemorrhage after 32 hours. However, after 24 hours all tested guinea pigs showed less inhibition (<60%) compared to that obtained after 32 hours. The outcome of this study reflects that the extract of H. aethiopicus plant may contain an endogenous inhibitor of venom induced local haemorrhage. PMID- 22666295 TI - Thermographical measuring of the skin temperature using laser needle acupuncture in preterm neonates. AB - In children, laser acupuncture is used more often than needle acupuncture in Western countries, due to their aversion to needles. When applying laser acupuncture to premature babies and neonates, firstly the degree of the thermal increase to the skin has to be evaluated so as to guarantee safe application. The patients were premature neonates before their discharge from hospital. The measurements were carried out by means of a polygraphy while they were asleep shortly. The large intestine 4 acupoint (LI4, Hegu) was stimulated by a microlaser needle (10 mW, 685 nm) twice (5 and 10 min). Local thermographic pictures were taken with a thermal camera (Flir i5, Flir Systems Inc., Portland, USA), and the warmest point was determined and subsequently compared. The study included 10 premature neonates (7 male, 3 female). The measurements were carried out on the 33rd day of life (weight 2030 g, gestational age 36 + 3 weeks of pregnancy). In comparison to the initial temperature (32.9 degrees C), after 5 minutes of stimulation (33.9 degrees C) (P = 0.025) and also after 10 minutes of stimulation (34.0 degrees C) (P = 0.01), there was found to be a significant increase in the skin temperature. The singular maximum value of 37.9 degrees C bears a potential danger; however, compared to the local temperatures reached in transcutaneous blood gas measurements it appears not to entail any risks. PMID- 22666296 TI - Morphologic and pharmacological investigations in the epicatechin gastroprotective effect. AB - Previous studies of the gastroprotective activity of plants have highlighted the importance of the polyphenolic compound epicatechin (EC) in the treatment of gastric ulcers. This paper aimed to evaluate and characterize the gastroprotective mechanism of action of EC using male rats. The gastroprotective action of EC was analyzed in gastric ulcers induced by ethanol or indomethacin. The involvement of sulfhydryl (SH) groups, K(+) (ATP) channels, alpha(2) adrenoceptors, gastric antisecretory activity, and the amount of mucus in the development of gastric ulcers were investigated. The lowest effective dose of EC providing gastroprotective effects was 50 mg/kg in the ethanol-induced gastric ulcers and 25 mg/kg in the indomethacin-induced gastric ulcers. The gastroprotection seen upon treatment with EC was significantly decreased in rats pretreated with a SH compound reagent or an alpha(2)-receptor antagonist, but not with a K(+) (ATP) channel blocker. Furthermore, oral treatment with EC increased mucus production and decreased H(+) secretion. Immunohistochemistry demonstrated the involvement of superoxide dismutase (SOD), nitric oxide (NO), and heat shock protein-70 (HSP-70) in the gastroprotection. These results demonstrate that EC provides gastroprotection through reinforcement of the mucus barrier and neutralization of gastric juice and this protection occurs through the involvement of SH compounds, alpha(2)-adrenoceptors, NO, SOD, and HSP-70. PMID- 22666297 TI - Characteristics and clinical managements of chronic skin ulcers based on traditional chinese medicine. AB - Chronic skin ulcer (CSU), including diabetic ulcers, venous ulcers, radiation ulcers, and pressure ulcers, remains a great challenge in the clinic. CSU seriously affects the quality of life of patients and requires long-term dedicated care, causing immense socioeconomic costs. CSU can cause the loss of the integrity of large portions of the skin, even leading to morbidity and mortality. Chinese doctors have used traditional Chinese medicine (TCM) for the treatment of CSU for many years and have accumulated much experience in clinical practice by combining systemic regulation and tropical treatment of CSU. Here, we discuss the classification and pathogenic process of CSU and strategies of TCM for the intervention of CSU, according to the theories of TCM. Particularly, we describe the potential intervenient strategies of the "qing-hua-bu" protocol with dynamic and combinational TCM therapies for different syndromes of CSU. PMID- 22666298 TI - Centella asiatica (L.) Urban: From Traditional Medicine to Modern Medicine with Neuroprotective Potential. AB - This paper covers the studies relevant to neuroprotective activity of Centella asiatica (L.) Urban, also known as "Gotu Kola." The plant is native to the Southeast Asia and has been used traditionally as brain tonic in ayurvedic medicine. The neuroprotective effect of C. asiatica has been searched using the key words "Centella, Centella asiatica, gotu kola, Asiatic pennywort, neuroprotection, and memory" through the electronic databases including Sciencedirect, Web of Science, Scopus, Pubmed, and Google Scholar. According to the literature survey, C. asiatica (gotu kola) has been reported to have a comprehensive neuroprotection by different modes of action such as enzyme inhibition, prevention of amyloid plaque formation in Alzheimer's disease, dopamine neurotoxicity in Parkinson's disease, and decreasing oxidative stress. Therefore, C. asiatica could be suggested to be a desired phytopharmaceutical with neuroprotective effect emerged from traditional medicine. PMID- 22666299 TI - Combining ZHENG Theory and High-Throughput Expression Data to Predict New Effects of Chinese Herbal Formulae. AB - ZHENG is the key theory in traditional Chinese medicine (TCM) and it is very important to find the molecular pharmacology of traditional Chinese herbal formulae. One ZHENG is related to many diseases and the herbal formulae are aiming to ZHENG. Therefore, many herbal formulae whose effects on a certain disease have been confirmed might also treat other diseases with the same ZHENG. In this study, the microarrays collected from patients with QiXuXueYu ZHENG (Qi deficiency and Blood-stasis syndrome) before treatment and after being treated with Fuzheng Huayu Capsule were analyzed by a high-throughput gene microarrays based drug similarity comparison method, which could find the small molecules which had similar effects with Fuzheng Huayu Capsule. Besides getting the results of anti-inflammatory and anti-fibrosis drugs which embody the known effect of Fuzheng Huayu Capsule, many other small molecules were screened out and could reflect other types of effects of this formula in treating QiXuXueYu ZHENG, including anti-hyperglycemic, anti-hyperlipidemic, hyposenstive effect. Then we integrated this information to display the effect of Fuzheng Huayu Capsule and its potential multiple-target molecular pharmacology. Moreover, through using clinical blood-tested data to verify our prediction, Fuzheng Huayu Capsule was proved to have effects on diabetes and dyslipidemia. PMID- 22666300 TI - Measuring connectivity in linear multivariate processes: definitions, interpretation, and practical analysis. AB - This tutorial paper introduces a common framework for the evaluation of widely used frequency-domain measures of coupling (coherence, partial coherence) and causality (directed coherence, partial directed coherence) from the parametric representation of linear multivariate (MV) processes. After providing a comprehensive time-domain definition of the various forms of connectivity observed in MV processes, we particularize them to MV autoregressive (MVAR) processes and derive the corresponding frequency-domain measures. Then, we discuss the theoretical interpretation of these MVAR-based connectivity measures, showing that each of them reflects a specific time-domain connectivity definition and how this results in the description of peculiar aspects of the information transfer in MV processes. Furthermore, issues related to the practical utilization of these measures on real-time series are pointed out, including MVAR model estimation and significance assessment. Finally, limitations and pitfalls arising from model mis-specification are discussed, indicating possible solutions and providing practical recommendations for a safe computation of the connectivity measures. An example of estimation of the presented measures from multiple EEG signals recorded during a combined visuomotor task is also reported, showing how evaluation of coupling and causality in the frequency domain may help describing specific neurophysiological mechanisms. PMID- 22666301 TI - The height gain in scoliotic deformity correction: assessed by new predictive formula. AB - Height gain after scoliosis correction is of a special interest for the patient and family. Ylikoski was the first to suggest a formula predicting height loss in untreated scoliotic patients. Stokes has recently suggested a new formula by using Cobb angle to determine height loss in idiopathic curves. We hypothesized that new additional variables to Cobb angle such as apical vertebral translation (AVT), number of instrumented segments (N), and disc heights may increase the accuracy of predicted height gain. According to our findings simple expression for height gain by simplified version of the formula is: SPDeltaH = 0.0059X(1)theta(1) + 2.3(1 - (theta(2)/theta(1)))N, where theta(1) is preoperative Cobb angle, X(1) is preoperative AVT, theta(2) is postoperative Cobb angle, and N is the number of instrumented vertebra. The purpose of this study is to analyze a new mathematical formula to predict height gain after scoliotic deformity correction. PMID- 22666302 TI - Nonlinear phenomena in biology and medicine. PMID- 22666303 TI - Effect of relative marker movement on the calculation of the foot torsion axis using a combined Cardan angle and helical axis approach. AB - The two main movements occurring between the forefoot and rearfoot segment of a human foot are flexion at the metatarsophalangeal joints and torsion in the midfoot. The location of the torsion axis within the foot is currently unknown. The purpose of this study was to develop a method based on Cardan angles and the finite helical axis approach to calculate the torsion axis without the effect of flexion. As the finite helical axis method is susceptible to error due to noise with small helical rotations, a minimal amount of rotation was defined in order to accurately determine the torsion axis location. Using simulation, the location of the axis based on data containing noise was compared to the axis location of data without noise with a one-sample t-test and Fisher's combined probability score. When using only data with helical rotation of seven degrees or more, the location of the torsion axis based on the data with noise was within 0.2 mm of the reference location. Therefore, the proposed method allowed an accurate calculation of the foot torsion axis location. PMID- 22666304 TI - Theoretical compartment modeling of DCE-MRI data based on the transport across physiological barriers in the brain. AB - Neurological disorders represent major causes of lost years of healthy life and mortality worldwide. Development of their quantitative interdisciplinary in vivo evaluation is required. Compartment modeling (CM) of brain data acquired in vivo using magnetic resonance imaging techniques with clinically available contrast agents can be performed to quantitatively assess brain perfusion. Transport of (1)H spins in water molecules across physiological compartmental brain barriers in three different pools was mathematically modeled and theoretically evaluated in this paper and the corresponding theoretical compartment modeling of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) data was analyzed. The pools considered were blood, tissue, and cerebrospinal fluid (CSF). The blood and CSF data were mathematically modeled assuming continuous flow of the (1)H spins in these pools. Tissue data was modeled using three CMs. Results in this paper show that transport across physiological brain barriers such as the blood to brain barrier, the extracellular space to the intracellular space barrier, or the blood to CSF barrier can be evaluated quantitatively. Statistical evaluations of this quantitative information may be performed to assess tissue perfusion, barriers' integrity, and CSF flow in vivo in the normal or disease-affected brain or to assess response to therapy. PMID- 22666305 TI - Extraction of nucleolus candidate zone in white blood cells of peripheral blood smear images using curvelet transform. AB - The main part of each white blood cell (WBC) is its nucleus which contains chromosomes. Although white blood cells (WBCs) with giant nuclei are the main symptom of leukemia, they are not sufficient to prove this disease and other symptoms must be investigated. For example another important symptom of leukemia is the existence of nucleolus in nucleus. The nucleus contains chromatin and a structure called the nucleolus. Chromatin is DNA in its active form while nucleolus is composed of protein and RNA, which are usually inactive. In this paper, to diagnose this symptom and in order to discriminate between nucleoli and chromatins, we employ curvelet transform, which is a multiresolution transform for detecting 2D singularities in images. For this reason, at first nuclei are extracted by means of K-means method, then curvelet transform is applied on extracted nuclei and the coefficients are modified, and finally reconstructed image is used to extract the candidate locations of chromatins and nucleoli. This method is applied on 100 microscopic images and succeeds with specificity of 80.2% and sensitivity of 84.3% to detect the nucleolus candidate zone. After nucleolus candidate zone detection, new features that can be used to classify atypical and blast cells such as gradient of saturation channel are extracted. PMID- 22666306 TI - An analytical approach to network motif detection in samples of networks with pairwise different vertex labels. AB - Network motifs, overrepresented small local connection patterns, are assumed to act as functional meaningful building blocks of a network and, therefore, received considerable attention for being useful for understanding design principles and functioning of networks. We present an extension of the original approach to network motif detection in single, directed networks without vertex labeling to the case of a sample of directed networks with pairwise different vertex labels. A characteristic feature of this approach to network motif detection is that subnetwork counts are derived from the whole sample and the statistical tests are adjusted accordingly to assign significance to the counts. The associated computations are efficient since no simulations of random networks are involved. The motifs obtained by this approach also comprise the vertex labeling and its associated information and are characteristic of the sample. Finally, we apply this approach to describe the intricate topology of a sample of vertex-labeled networks which originate from a previous EEG study, where the processing of painful intracutaneous electrical stimuli and directed interactions within the neuromatrix of pain in patients with major depression and healthy controls was investigated. We demonstrate that the presented approach yields characteristic patterns of directed interactions while preserving their important topological information and omitting less relevant interactions. PMID- 22666307 TI - Human resources issues and Australian Disaster Medical Assistance Teams: results of a national survey of team members. AB - BACKGROUND: Calls for disaster medical assistance teams (DMATs) are likely to continue in response to international disasters. As part of a national survey, this study was designed to evaluate Australian DMAT experience in relation to the human resources issues associated with deployment. METHODS: Data was collected via an anonymous mailed survey distributed via State and Territory representatives on the Australian Health Protection Committee, who identified team members associated with Australian DMAT deployments from the 2004 South East Asian Tsunami disaster. RESULTS: The response rate for this survey was 50% (59/118). Most personnel had deployed to the Asian Tsunami affected areas with DMAT members having significant clinical and international experience. While all except one respondent stated they received a full orientation prior to deployment, only 34% of respondents (20/59) felt their role was clearly defined pre deployment. Approximately 56% (33/59) felt their actual role matched their intended role and that their clinical background was well suited to their tasks. Most respondents were prepared to be available for deployment for 1 month (34%, 20/59). The most common period of notice needed to deploy was 6-12 hours for 29% (17/59) followed by 12-24 hours for 24% (14/59). The preferred period of overseas deployment was 14-21 days (46%, 27/59) followed by 1 month (25%, 15/59) and the optimum shift period was felt to be 12 hours by 66% (39/59). The majority felt that there was both adequate pay (71%, 42/59) and adequate indemnity (66%, 39/59). Almost half (49%, 29/59) stated it was better to work with people from the same hospital and, while most felt their deployment could be easily covered by staff from their workplace (56%, 33/59) and caused an inconvenience to their colleagues (51%, 30/59), it was less likely to interrupt service delivery in their workplace (10%, 6/59) or cause an inconvenience to patients (9%, 5/59). Deployment was felt to benefit the affected community by nearly all (95%, 56/59) while less (42%, 25/59) felt that there was a benefit for their own local community. Nearly all felt their role was recognised on return (93%, 55/59) and an identical number (93%, 55/59) enjoyed the experience. All stated they would volunteer again, with 88% strongly agreeing with this statement. CONCLUSIONS: This study of Australian DMAT members provides significant insights into a number of human resources issues and should help guide future deployments. The preferred 'on call' arrangements, notice to deploy, period of overseas deployment and shift length are all identified. This extended period of operations needs to be supported by planning and provision of rest cycles, food, temporary accommodation and rest areas for staff. The study also suggests that more emphasis should be placed on team selection and clarification of roles. While the majority felt that there was both adequate pay and adequate indemnity, further work clarifying this, based on national conditions of service should be, and are, being explored currently by the state based teams in Australia. Importantly, the deployment was viewed positively by team members who all stated they would volunteer again, which allows the development of an experienced cohort of team members. PMID- 22666308 TI - Identification of functional differences in metabolic networks using comparative genomics and constraint-based models. AB - Genome-scale network reconstructions are useful tools for understanding cellular metabolism, and comparisons of such reconstructions can provide insight into metabolic differences between organisms. Recent efforts toward comparing genome scale models have focused primarily on aligning metabolic networks at the reaction level and then looking at differences and similarities in reaction and gene content. However, these reaction comparison approaches are time-consuming and do not identify the effect network differences have on the functional states of the network. We have developed a bilevel mixed-integer programming approach, CONGA, to identify functional differences between metabolic networks by comparing network reconstructions aligned at the gene level. We first identify orthologous genes across two reconstructions and then use CONGA to identify conditions under which differences in gene content give rise to differences in metabolic capabilities. By seeking genes whose deletion in one or both models disproportionately changes flux through a selected reaction (e.g., growth or by product secretion) in one model over another, we are able to identify structural metabolic network differences enabling unique metabolic capabilities. Using CONGA, we explore functional differences between two metabolic reconstructions of Escherichia coli and identify a set of reactions responsible for chemical production differences between the two models. We also use this approach to aid in the development of a genome-scale model of Synechococcus sp. PCC 7002. Finally, we propose potential antimicrobial targets in Mycobacterium tuberculosis and Staphylococcus aureus based on differences in their metabolic capabilities. Through these examples, we demonstrate that a gene-centric approach to comparing metabolic networks allows for a rapid comparison of metabolic models at a functional level. Using CONGA, we can identify differences in reaction and gene content which give rise to different functional predictions. Because CONGA provides a general framework, it can be applied to find functional differences across models and biological systems beyond those presented here. PMID- 22666310 TI - Membrane-bound TNF induces protective immune responses to M. bovis BCG infection: regulation of memTNF and TNF receptors comparing two memTNF molecules. AB - BACKGROUND: Several activities of the transmembrane form of TNF (memTNF) in immune responses to intracellular bacterial infection have been shown to be different from those exerted by soluble TNF. Evidence is based largely on studies in transgenic mice expressing memTNF, but precise cellular mechanisms are not well defined and the importance of TNF receptor regulation is unknown. In addition, memTNF activities are defined for a particular modification of the extracellular domain of TNF but a direct comparison of different mutant memTNF molecules has not been done in vivo. METHODOLOGY: To understand the activities of memTNF we compared two commonly used mouse strains lacking soluble TNF but possessing functional and normally regulated membrane-bound TNF knockin (memTNF KI) for their capacity to generate cell-mediated immune responses and resistance to M. bovis BCG infection, and to regulate TNF receptors. PRINCIPAL FINDINGS: M. bovis BCG infection resulted in similar bacterial loads in one strain of memTNF KI (memTNF(Delta1-9,K11E)) and in wild-type mice, in contrast, the other strain of memTNF KI mice (memTNF(Delta1-12)) showed higher sensitivity to infection with high mortality (75%), greater bacterial load and massive lung pathology. The pattern of cytokines/chemokines, inflammatory cells, pulmonary NF-kappaB phosphorylation, antigen-dependent IFN-gamma response, and splenic iNOS was impaired in M. bovis BCG-infected memTNF(Delta1-12) KI mice. Macrophages expressing TNFR2 were reduced but soluble TNFRs were higher in memTNF(Delta1-12) KI mice during the infection. In vitro, M. bovis BCG-induced NF-kappaB activation and cytokines were also decreased in memTNF(Delta1-12) KI bone marrow-derived macrophages. CONCLUSION: Our data show that two memTNF molecules exerted very different activities upon M. bovis BCG infection resulting in protection or not to bacterial infection. These results suggest a regulatory mechanism of memTNF and TNF receptors being critical in the outcome of the infection and highlight the role of cell-bound and soluble TNFR2 in memTNF-mediated anti-microbial mechanisms. PMID- 22666311 TI - Passive auditory stimulation improves vision in hemianopia. AB - Techniques employed in rehabilitation of visual field disorders such as hemianopia are usually based on either visual or audio-visual stimulation and patients have to perform a training task. Here we present results from a completely different, novel approach that was based on passive unimodal auditory stimulation. Ten patients with either left or right-sided pure hemianopia (without neglect) received one hour of unilateral passive auditory stimulation on either their anopic or their intact side by application of repetitive trains of sound pulses emitted simultaneously via two loudspeakers. Immediately before and after passive auditory stimulation as well as after a period of recovery, patients completed a simple visual task requiring detection of light flashes presented along the horizontal plane in total darkness. The results showed that one-time passive auditory stimulation on the side of the blind, but not of the intact, hemifield of patients with hemianopia induced an improvement in visual detections by almost 100% within 30 min after passive auditory stimulation. This enhancement in performance was reversible and was reduced to baseline 1.5 h later. A non-significant trend of a shift of the visual field border toward the blind hemifield was obtained after passive auditory stimulation. These results are compatible with the view that passive auditory stimulation elicited some activation of the residual visual pathways, which are known to be multisensory and may also be sensitive to unimodal auditory stimuli as were used here. TRIAL REGISTRATION: DRKS00003577. PMID- 22666312 TI - The Mice Drawer System (MDS) experiment and the space endurance record-breaking mice. AB - The Italian Space Agency, in line with its scientific strategies and the National Utilization Plan for the International Space Station (ISS), contracted Thales Alenia Space Italia to design and build a spaceflight payload for rodent research on ISS: the Mice Drawer System (MDS). The payload, to be integrated inside the Space Shuttle middeck during transportation and inside the Express Rack in the ISS during experiment execution, was designed to function autonomously for more than 3 months and to involve crew only for maintenance activities. In its first mission, three wild type (Wt) and three transgenic male mice over-expressing pleiotrophin under the control of a bone-specific promoter (PTN-Tg) were housed in the MDS. At the time of launch, animals were 2-months old. MDS reached the ISS on board of Shuttle Discovery Flight 17A/STS-128 on August 28(th), 2009. MDS returned to Earth on November 27(th), 2009 with Shuttle Atlantis Flight ULF3/STS 129 after 91 days, performing the longest permanence of mice in space. Unfortunately, during the MDS mission, one PTN-Tg and two Wt mice died due to health status or payload-related reasons. The remaining mice showed a normal behavior throughout the experiment and appeared in excellent health conditions at landing. During the experiment, the mice health conditions and their water and food consumption were daily checked. Upon landing mice were sacrificed, blood parameters measured and tissues dissected for subsequent analysis. To obtain as much information as possible on microgravity-induced tissue modifications, we organized a Tissue Sharing Program: 20 research groups from 6 countries participated. In order to distinguish between possible effects of the MDS housing conditions and effects due to the near-zero gravity environment, a ground replica of the flight experiment was performed at the University of Genova. Control tissues were collected also from mice maintained on Earth in standard vivarium cages. PMID- 22666313 TI - Convergent evidence from mouse and human studies suggests the involvement of zinc finger protein 326 gene in antidepressant treatment response. AB - OBJECTIVES: The forced swim test (FST) is a commonly used model to predict antidepressant efficacy. Uncovering the genetic basis of the model may unravel the mechanism of antidepressant treatment. METHODS: FVB/NJ (FVB) and C57BL/6J (B6) were first identified as the response and non-response strains to fluoxetine (a serotonin-specific reuptake inhibitor antidepressant) treatment in the mouse FST. Simple-interval (SIM) and composite-interval (CIM) mappings were applied to map the quantitative trait loci (QTLs) of the anti-immobility effect of fluoxetine in FST (FST(FLX)) in 865 male B6*FVB-F2 mice. The brain mRNA expressions of the gene with the maximum QTL-linkage signal for FST(FLX) after the FST were compared between B6 and FVB mice and also compared between fluoxetine and saline treatment. The association of the variants in the human homologue of the mouse FST(FLX)-QTL gene with major depressive disorder (MDD) and antidepressant response were investigated in 1080 human subjects (MDD/control = 582/498). RESULTS: One linkage signal for FST(FLX)-QTL was detected at an intronic SNP (rs6215396) of the mouse Zfp326 gene (maximal CIM-LOD = 9.36). The Zfp326 mRNA expression in the FVB thalamus was significantly down-regulated by fluoxetine in the FST, and the higher FVB-to-B6 Zfp326 mRNA expressions in the frontal cortex, striatum and hypothalamus diminished after fluoxetine treatment. Two coding-synonymous SNPs (rs2816881 and rs10922744) in the human homologue of Zfp326, ZNF326, were significantly associated with the 8-week antidepressant treatment response in the MDD patients (Bonferroni-corrected p = 0.004-0.028). CONCLUSIONS: The findings suggest the involvement of the Zfp326 and ZNF326 genes in antidepressant treatment response. PMID- 22666314 TI - Breast cancer 1 (BrCa1) may be behind decreased lipogenesis in adipose tissue from obese subjects. AB - CONTEXT: Expression and activity of the main lipogenic enzymes is paradoxically decreased in obesity, but the mechanisms behind these findings are poorly known. Breast Cancer 1 (BrCa1) interacts with acetyl-CoA carboxylase (ACC) reducing the rate of fatty acid biosynthesis. In this study, we aimed to evaluate BrCa1 in human adipose tissue according to obesity and insulin resistance, and in vitro cultured adipocytes. RESEARCH DESIGN AND METHODS: BrCa1 gene expression, total and phosphorylated (P-) BrCa1, and ACC were analyzed in adipose tissue samples obtained from a total sample of 133 subjects. BrCa1 expression was also evaluated during in vitro differentiation of human adipocytes and 3T3-L1 cells. RESULTS: BrCa1 gene expression was significantly up-regulated in both omental (OM; 1.36 fold, p = 0.002) and subcutaneous (SC; 1.49-fold, p = 0.001) adipose tissue from obese subjects. In parallel with increased BrCa1 mRNA, P-ACC was also up regulated in SC (p = 0.007) as well as in OM (p = 0.010) fat from obese subjects. Consistent with its role limiting fatty acid biosynthesis, both BrCa1 mRNA (3.5 fold, p<0.0001) and protein (1.2-fold, p = 0.001) were increased in pre adipocytes, and decreased during in vitro adipogenesis, while P-ACC decreased during differentiation of human adipocytes (p = 0.005) allowing lipid biosynthesis. Interestingly, BrCa1 gene expression in mature adipocytes was restored by inflammatory stimuli (macrophage conditioned medium), whereas lipogenic genes significantly decreased. CONCLUSIONS: The specular findings of BrCa1 and lipogenic enzymes in adipose tissue and adipocytes reported here suggest that BrCa1 might help to control fatty acid biosynthesis in adipocytes and adipose tissue from obese subjects. PMID- 22666315 TI - Evolution and association analysis of Ghd7 in rice. AB - Plant height, heading date, and yield are the main targets for rice genetic improvement. Ghd7 is a pleiotropic gene that controls the aforementioned traits simultaneously. In this study, a rice germplasm collection of 104 accessions (Oryza sativa) and 3 wild rice varieties (O.rufipogon) was used to analyze the evolution and association of Ghd7 with plant height, heading date, and yield. Among the 104 accessions, 76 single nucleotide polymorphisms (SNPs) and six insertions and deletions were found within a 3932-bp DNA fragment of Ghd7. A higher pairwise pi and theta in the promoter indicated a highly diversified promoter of Ghd7. Sixteen haplotypes and 8 types of Ghd7 protein were detected. SNP changes between haplotypes indicated that Ghd7 evolved from two distinct ancestral gene pools, and independent domestication processes were detected in indica and japonica varietals respectively. In addition to the previously reported premature stop mutation in the first exon of Ghd7, which caused phenotypic changes of multiple traits, we found another functional C/T mutation (SNP S_555) by structure-based association analysis. SNP S_555 is located in the promoter and was related to plant height probably by altering gene expression. Moreover, another seven SNP mutations in complete linkage were found to be associated with the number of spikelets per panicle, regardless of the photoperiod. These associations provide the potential for flexibility of Ghd7 application in rice breeding programs. PMID- 22666316 TI - Estimating the richness of a population when the maximum number of classes is fixed: a nonparametric solution to an archaeological problem. AB - BACKGROUND: Estimating assemblage species or class richness from samples remains a challenging, but essential, goal. Though a variety of statistical tools for estimating species or class richness have been developed, they are all singly bounded: assuming only a lower bound of species or classes. Nevertheless there are numerous situations, particularly in the cultural realm, where the maximum number of classes is fixed. For this reason, a new method is needed to estimate richness when both upper and lower bounds are known. METHODOLOGY/PRINCIPAL FINDINGS: Here, we introduce a new method for estimating class richness: doubly bounded confidence intervals (both lower and upper bounds are known). We specifically illustrate our new method using the Chao1 estimator, rarefaction, and extrapolation, although any estimator of asymptotic richness can be used in our method. Using a case study of Clovis stone tools from the North American Lower Great Lakes region, we demonstrate that singly-bounded richness estimators can yield confidence intervals with upper bound estimates larger than the possible maximum number of classes, while our new method provides estimates that make empirical sense. CONCLUSIONS/SIGNIFICANCE: Application of the new method for constructing doubly-bound richness estimates of Clovis stone tools permitted conclusions to be drawn that were not otherwise possible with singly-bounded richness estimates, namely, that Lower Great Lakes Clovis Paleoindians utilized a settlement pattern that was probably more logistical in nature than residential. However, our new method is not limited to archaeological applications. It can be applied to any set of data for which there is a fixed maximum number of classes, whether that be site occupancy models, commercial products (e.g. athletic shoes), or census information (e.g. nationality, religion, age, race). PMID- 22666317 TI - Glycans in sera of amyotrophic lateral sclerosis patients and their role in killing neuronal cells. AB - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease caused by degeneration of upper and lower motor neurons. To date, glycosylation patterns of glycoproteins in fluids of ALS patients have not been described. Moreover, the aberrant glycosylation related to the pathogenesis of other neurodegenerative diseases encouraged us to explore the glycome of ALS patient sera. We found high levels of sialylated glycans and low levels of core fucosylated glycans in serum derived N-glycans of patients with ALS, compared to healthy volunteer sera. Based on these results, we analyzed the IgG Fc N(297)-glycans, as IgG are major serum glycoproteins affected by sialylation or core fucosylation and are found in the motor cortex of ALS patients. The analyses revealed a distinct glycan, A2BG2, in IgG derived from ALS patient sera (ALS-IgG). This glycan increases the affinity of IgG to CD16 on effector cells, consequently enhancing Antibody-Dependent Cellular Cytotoxicity (ADCC). Therefore, we explore whether the Fc-N(297)-glycans of IgG may be involved in ALS disease. Immunostaining of brain and spinal cord tissues revealed over-expression of CD16 and co-localization of intact ALS-IgG with CD16 and in brain with activated microglia of G93A-SOD1 mice. Intact ALS-IgG enhanced effector cell activation and ADCC reaction in comparison to sugar depleted or control IgG. ALS-IgG were localized in the synapse between brain microglia and neurons of G93A-SOD1 mice, manifesting a promising in vivo ADCC reaction. Therefore, glycans of ALS-IgG may serve as a biomarker for the disease and may be involved in neuronal damage. PMID- 22666318 TI - Tumour cell generation of inducible regulatory T-cells in multiple myeloma is contact-dependent and antigen-presenting cell-independent. AB - Regulatory T-cells (T(Reg) cells) are increased in patients with multiple myeloma (MM). We investigated whether MM cells could generate and/or expand T(Reg) cells as a method of immuno-surveillance avoidance. In an in vitro model, CD4(+)CD25( )FoxP3(-) T-cells co-cultured with malignant plasma cells (primary MM cells and cell lines) induced a significant generation of CD4(+)CD25(+)FoxP3(+) inducible T(Reg) cells (tT(Reg) cells; p<0.0001), in a contact-dependent manner. tT(Reg) cells were polyclonal, demonstrated a suppressive phenotype and phenotypically, demonstrated increased FoxP3 (p = 0.0001), increased GITR (p<0.0001), increased PD1 (p = 0.003) and decreased CD62L (p = 0.007) expression compared with naturally occurring T(Reg) cells. FACS-sorted tT(Reg) cells differentiated into FoxP(+)IL-17(+) and FoxP3(-)IL-17(+) CD4(+) cells upon TCR-mediated stimulation. Blocking experiments with anti-ICOS-L MoAb resulted in a significant inhibition of tT(Reg) cell generation whereas both IL-10 & TGFbeta blockade did not. MM tumour cells can directly generate functional T(Reg) cells in a contact-dependent manner, mediated by ICOS/ICOS-L. These features suggest that tumour generation of T(Reg) cells may contribute to evasion of immune surveillance by the host. PMID- 22666320 TI - An assessment of the impact of hafting on Paleoindian point variability. AB - It has long been argued that the form of North American Paleoindian points was affected by hafting. According to this hypothesis, hafting constrained point bases such that they are less variable than point blades. The results of several studies have been claimed to be consistent with this hypothesis. However, there are reasons to be skeptical of these results. None of the studies employed statistical tests, and all of them focused on points recovered from kill and camp sites, which makes it difficult to be certain that the differences in variability are the result of hafting rather than a consequence of resharpening. Here, we report a study in which we tested the predictions of the hafting hypothesis by statistically comparing the variability of different parts of Clovis points. We controlled for the potentially confounding effects of resharpening by analyzing largely unused points from caches as well as points from kill and camp sites. The results of our analyses were not consistent with the predictions of the hypothesis. We found that several blade characters and point thickness were no more variable than the base characters. Our results indicate that the hafting hypothesis does not hold for Clovis points and indicate that there is a need to test its applicability in relation to post-Clovis Paleoindian points. PMID- 22666319 TI - Modulation of human mesenchymal stem cell immunogenicity through forced expression of human cytomegalovirus us proteins. AB - BACKGROUND: Mesenchymal stem cells (MSC) are promising candidates for cell therapy, as they migrate to areas of injury, differentiate into a broad range of specialized cells, and have immunomodulatory properties. However, MSC are not invisible to the recipient's immune system, and upon in vivo administration, allogeneic MSC are able to trigger immune responses, resulting in rejection of the transplanted cells, precluding their full therapeutic potential. Human cytomegalovirus (HCMV) has developed several strategies to evade cytotoxic T lymphocyte (CTL) and Natural Killer (NK) cell recognition. Our goal is to exploit HCMV immunological evasion strategies to reduce MSC immunogenicity. METHODOLOGY/PRINCIPAL FINDINGS: We genetically engineered human MSC to express HCMV proteins known to downregulate HLA-I expression, and investigated whether modified MSC were protected from CTL and NK attack. Flow cytometric analysis showed that amongst the US proteins tested, US6 and US11 efficiently reduced MSC HLA-I expression, and mixed lymphocyte reaction demonstrated a corresponding decrease in human and sheep mononuclear cell proliferation. NK killing assays showed that the decrease in HLA-I expression did not result in increased NK cytotoxicity, and that at certain NK?MSC ratios, US11 conferred protection from NK cytotoxic effects. Transplantation of MSC-US6 or MSC-US11 into pre-immune fetal sheep resulted in increased liver engraftment when compared to control MSC, as demonstrated by qPCR and immunofluorescence analyses. CONCLUSIONS AND SIGNIFICANCE: These data demonstrate that engineering MSC to express US6 and US11 can be used as a means of decreasing recognition of MSC by the immune system, allowing higher levels of engraftment in an allogeneic transplantation setting. Since one of the major factors responsible for the failure of allogeneic-donor MSC to engraft is the mismatch of HLA-I molecules between the donor and the recipient, MSC-US6 and MSC-US11 could constitute an off-the-shelf product to overcome donor-recipient HLA-I mismatch. PMID- 22666321 TI - Protection of Spanish Ibex (Capra pyrenaica) against Bluetongue virus serotypes 1 and 8 in a subclinical experimental infection. AB - Many wild ruminants such as Spanish ibex (Capra pyrenaica) are susceptible to Bluetongue virus (BTV) infection, which causes disease mainly in domestic sheep and cattle. Outbreaks involving either BTV serotypes 1 (BTV-1) and 8 (BTV-8) are currently challenging Europe. Inclusion of wildlife vaccination among BTV control measures should be considered in certain species. In the present study, four out of fifteen seronegative Spanish ibexes were immunized with a single dose of inactivated vaccine against BTV-1, four against BTV-8 and seven ibexes were non vaccinated controls. Seven ibexes (four vaccinated and three controls) were inoculated with each BTV serotype. Antibody and IFN-gamma responses were evaluated until 28 days after inoculation (dpi). The vaccinated ibexes showed significant (P<0.05) neutralizing antibody levels after vaccination compared to non vaccinated ibexes. The non vaccinated ibexes remained seronegative until challenge and showed neutralizing antibodies from 7 dpi. BTV RNA was detected in the blood of non vaccinated ibexes from 2 to the end of the study (28 dpi) and in target tissue samples obtained at necropsy (8 and 28 dpi). BTV-1 was successfully isolated on cell culture from blood and target tissues of non vaccinated ibexes. Clinical signs were unapparent and no gross lesions were found at necropsy. Our results show for the first time that Spanish ibex is susceptible and asymptomatic to BTV infection and also that a single dose of vaccine prevents viraemia against BTV-1 and BTV-8 replication. PMID- 22666322 TI - Nicotinic receptor Alpha7 expression during tooth morphogenesis reveals functional pleiotropy. AB - The expression of nicotinic acetylcholine receptor (nAChR) subtype, alpha7, was investigated in the developing teeth of mice that were modified through homologous recombination to express a bi-cistronic IRES-driven tau-enhanced green fluorescent protein (GFP); alpha7GFP) or IRES-Cre (alpha7Cre). The expression of alpha7GFP was detected first in cells of the condensing mesenchyme at embryonic (E) day E13.5 where it intensifies through E14.5. This expression ends abruptly at E15.5, but was again observed in ameloblasts of incisors at E16.5 or molar ameloblasts by E17.5-E18.5. This expression remains detectable until molar enamel deposition is completed or throughout life as in the constantly erupting mouse incisors. The expression of alpha7GFP also identifies all stages of innervation of the tooth organ. Ablation of the alpha7-cell lineage using a conditional alpha7Cre*ROSA26-LoxP(diphtheria toxin A) strategy substantially reduced the mesenchyme and this corresponded with excessive epithelium overgrowth consistent with an instructive role by these cells during ectoderm patterning. However, alpha7knock-out (KO) mice exhibited normal tooth size and shape indicating that under normal conditions alpha7 expression is dispensable to this process. The function of ameloblasts in alpha7KO mice is altered relative to controls. High resolution micro-computed tomography analysis of adult mandibular incisors revealed enamel volume of the alpha7KO was significantly reduced and the organization of enamel rods was altered relative to controls. These results demonstrate distinct and varied spatiotemporal expression of alpha7 during tooth development, and they suggest that dysfunction of this receptor would have diverse impacts upon the adult organ. PMID- 22666324 TI - Functional morphometric analysis of the furcula in mesozoic birds. AB - The furcula displays enormous morphological and structural diversity. Acting as an important origin for flight muscles involved in the downstroke, the form of this element has been shown to vary with flight mode. This study seeks to clarify the strength of this form-function relationship through the use of eigenshape morphometric analysis coupled with recently developed phylogenetic comparative methods (PCMs), including phylogenetic Flexible Discriminant Analysis (pFDA). Additionally, the morphospace derived from the furculae of extant birds is used to shed light on possible flight adaptations of Mesozoic fossil taxa. While broad conclusions of earlier work are supported (U-shaped furculae are associated with soaring, strong anteroposterior curvature with wing-propelled diving), correlations between form and function do not appear to be so clear-cut, likely due to the significantly larger dataset and wider spectrum of flight modes sampled here. Interclavicular angle is an even more powerful discriminator of flight mode than curvature, and is positively correlated with body size. With the exception of the close relatives of modern birds, the ornithuromorphs, Mesozoic taxa tend to occupy unique regions of morphospace, and thus may have either evolved unfamiliar flight styles or have arrived at similar styles through divergent musculoskeletal configurations. PMID- 22666323 TI - Genome-wide expression analysis identifies a modulator of ionizing radiation induced p53-independent apoptosis in Drosophila melanogaster. AB - Tumor suppressor p53 plays a key role in DNA damage responses in metazoa, yet more than half of human tumors show p53 deficiencies. Therefore, understanding how therapeutic genotoxins such as ionizing radiation (IR) can elicit DNA damage responses in a p53-independent manner is of clinical importance. Drosophila has been a good model to study the effects of IR because DNA damage responses as well as underlying genes are conserved in this model, and because streamlined gene families make loss-of-function analyses feasible. Indeed, Drosophila is the only genetically tractable model for IR-induced, p53-independent apoptosis and for tissue regeneration and homeostasis after radiation damage. While these phenomenon occur only in the larvae, all genome-wide gene expression analyses after irradiation to date have been in embryos. We report here the first analysis of IR-induced, genome-wide gene expression changes in wild type and p53 mutant Drosophila larvae. Key data from microarrays were confirmed by quantitative RT PCR. The results solidify the central role of p53 in IR-induced transcriptome changes, but also show that nearly all changes are made of both p53-dependent and p53-independent components. p53 is found to be necessary not just for the induction of but also for the repression of transcript levels for many genes in response to IR. Furthermore, Functional analysis of one of the top-changing genes, EF1a-100E, implicates it in repression of IR-induced p53-independent apoptosis. These and other results support the emerging notion that there is not a single dominant mechanism but that both positive and negative inputs collaborate to induce p53-independent apoptosis in response to IR in Drosophila larvae. PMID- 22666325 TI - Rituximab for children with immune thrombocytopenia: a systematic review. AB - BACKGROUND: Rituximab has been widely used off-label as a second line treatment for children with immune thrombocytopenia (ITP). However, its role in the management of pediatric ITP requires clarification. To understand and interpret the available evidence, we conducted a systematic review to assess the efficacy and safety of rituximab for children with ITP. METHODOLOGY/PRINCIPAL FINDINGS: We searched MEDLINE, EMBASE, Cochrane Library, CBM, CNKI, abstract databases of American Society of Hematology, American Society of Clinical Oncology and Pediatric Academic Society. Clinical studies published in full text or abstract only in any language that met predefined inclusion criteria were eligible. Efficacy analysis was restricted to studies enrolling 5 or more patients. Safety was evaluated from all studies that reported data of toxicity. 14 studies (323 patients) were included for efficacy assessment in children with primary ITP. The pooled complete response (platelet count >= 100 * 10(9)/L) and response (platelet count >= 30 * 10(9)/L) rate after rituximab treatment were 39% (95% CI, 30% to 49%) and 68% (95%CI, 58% to 77%), respectively, with median response duration of 12.8 month. 4 studies (29 patients) were included for efficacy assessment in children with secondary ITP. 11 (64.7%) of 17 patients associated with Evans syndrome achieved response. All 6 patients with systemic lupus erythematosus associated ITP and all 6 patients with autoimmune lymphoproliferative syndrome associated ITP achieved response. 91 patients experienced 108 adverse events associated with rituximab, among that, 91 (84.3%) were mild to moderate, and no death was reported. CONCLUSIONS/SIGNIFICANCE: Randomized controlled studies on effect of rituximab for children with ITP are urgently needed, although a series of uncontrolled studies found that rituximab resulted in a good platelet count response both in children with primary and children secondary ITP. Most adverse events associated with rituximab were mild to moderate, and no death was reported. PMID- 22666326 TI - 14-3-3epsilon Is required for germ cell migration in Drosophila. AB - Although 14-3-3 proteins participate in multiple biological processes, isoform specific specialized functions, as well as functional redundancy are emerging with tissue and developmental stage-specificity. Accordingly, the two 14-3 3epsilon proteins in Drosophila exhibit functional specificity and redundancy. Homozygotes for loss of function alleles of D14-3-3epsilon contain significantly fewer germ line cells (pole cells) in their gonads, a phenotype not shared by mutants in the other 14-3-3 gene leo. We show that although D14-3-3epsilon is enriched within pole cells it is required in mesodermal somatic gonad precursor cells which guide pole cells in their migration through the mesoderm and coalesce with them to form the embryonic gonad. Loss of D14-3-3epsilon results in defective pole cell migration, reduced pole cell number. We present evidence that D14-3-3epsilon loss results in reduction or loss of the transcription factor Zfh 1, one of the main regulatory molecules of the pole cell migration, from the somatic gonad precursor cells. PMID- 22666327 TI - A kinematic approach for efficient and robust simulation of the cardiac beating motion. AB - Computer simulation techniques for cardiac beating motions potentially have many applications and a broad audience. However, most existing methods require enormous computational costs and often show unstable behavior for extreme parameter sets, which interrupts smooth simulation study and make it difficult to apply them to interactive applications. To address this issue, we present an efficient and robust framework for simulating the cardiac beating motion. The global cardiac motion is generated by the accumulation of local myocardial fiber contractions. We compute such local-to-global deformations using a kinematic approach; we divide a heart mesh model into overlapping local regions, contract them independently according to fiber orientation, and compute a global shape that satisfies contracted shapes of all local regions as much as possible. A comparison between our method and a physics-based method showed that our method can generate motion very close to that of a physics-based simulation. Our kinematic method has high controllability; the simulated ventricle-wall contraction speed can be easily adjusted to that of a real heart by controlling local contraction timing. We demonstrate that our method achieves a highly realistic beating motion of a whole heart in real time on a consumer-level computer. Our method provides an important step to bridge a gap between cardiac simulations and interactive applications. PMID- 22666329 TI - Cloning and functional studies of a splice variant of CYP26B1 expressed in vascular cells. AB - BACKGROUND: All-trans retinoic acid (atRA) plays an essential role in the regulation of gene expression, cell growth and differentiation and is also important for normal cardiovascular development but may in turn be involved in cardiovascular diseases, i.e. atherosclerosis and restenosis. The cellular atRA levels are under strict control involving several cytochromes P450 isoforms (CYPs). CYP26 may be the most important regulator of atRA catabolism in vascular cells. The present study describes the molecular cloning, characterization and function of atRA-induced expression of a spliced variant of the CYP26B1 gene. METHODOLOGY/PRINCIPAL FINDINGS: The coding region of the spliced CYP26B1 lacking exon 2 was amplified from cDNA synthesized from atRA-treated human aortic smooth muscle cells and sequenced. Both the spliced variant and full length CYP26B1 was found to be expressed in cultured human endothelial and smooth muscle cells, and in normal and atherosclerotic vessel. atRA induced both variants of CYP26B1 in cultured vascular cells. Furthermore, the levels of spliced mRNA transcript were 4.5 times higher in the atherosclerotic lesion compared to normal arteries and the expression in the lesions was increased 20-fold upon atRA treatment. The spliced CYP26B1 still has the capability to degrade atRA, but at an initial rate one-third that of the corresponding full length enzyme. Transfection of COS-1 and THP-1 cells with the CYP26B1 spliced variant indicated either an increase or a decrease in the catabolism of atRA, probably depending on the expression of other atRA catabolizing enzymes in the cells. CONCLUSIONS/SIGNIFICANCE: Vascular cells express the spliced variant of CYP26B1 lacking exon 2 and it is also increased in atherosclerotic lesions. The spliced variant displays a slower and reduced degradation of atRA as compared to the full-length enzyme. Further studies are needed, however, to clarify the substrate specificity and role of the CYP26B1 splice variant in health and disease. PMID- 22666328 TI - A general strategy to endow natural fusion-protein-derived peptides with potent antiviral activity. AB - Fusion between the viral and target cell membranes is an obligatory step for the infectivity of all enveloped virus, and blocking this process is a clinically validated therapeutic strategy.Viral fusion is driven by specialized proteins which, although specific to each virus, act through a common mechanism, the formation of a complex between two heptad repeat (HR) regions. The HR regions are initially separated in an intermediate termed "prehairpin", which bridges the viral and cell membranes, and then fold onto each other to form a 6-helical bundle (6HB), driving the two membranes to fuse. HR-derived peptides can inhibit viral infectivity by binding to the prehairpin intermediate and preventing its transition to the 6HB.The antiviral activity of HR-derived peptides differs considerably among enveloped viruses. For weak inhibitors, potency can be increased by peptide engineering strategies, but sequence-specific optimization is time-consuming. In seeking ways to increase potency without changing the native sequence, we previously reported that attachment to the HR peptide of a cholesterol group ("cholesterol-tagging") dramatically increases its antiviral potency, and simultaneously increases its half-life in vivo. We show here that antiviral potency may be increased by combining cholesterol-tagging with dimerization of the HR-derived sequence, using as examples human parainfluenza virus, Nipah virus, and HIV-1. Together, cholesterol-tagging and dimerization may represent strategies to boost HR peptide potency to levels that in some cases may be compatible with in vivo use, possibly contributing to emergency responses to outbreaks of existing or novel viruses. PMID- 22666331 TI - A new saurolophine dinosaur from the latest cretaceous of far Eastern Russia. AB - BACKGROUND: Four main dinosaur sites have been investigated in latest cretaceous deposits from the Amur/Heilongjiang Region: Jiayin and Wulaga in China (Yuliangze Formation), Blagoveschensk and Kundur in Russia (Udurchukan Formation). More than 90% of the bones discovered in these localities belong to hollow-crested lambeosaurine saurolophids, but flat-headed saurolophines are also represented: Kerberosaurus manakini at Blagoveschensk and Wulagasaurus dongi at Wulaga. METHODOLOGY/PRINCIPAL FINDINGS: Herein we describe a new saurolophine dinosaur, Kundurosaurus nagornyi gen. et sp. nov., from the Udurchukan Formation (Maastrichtian) of Kundur, represented by disarticulated cranial and postcranial material. This new taxon is diagnosed by four autapomorphies. CONCLUSIONS/SIGNIFICANCE: A phylogenetic analysis of saurolophines indicates that Kundurosaurus nagornyi is nested within a rather robust clade including Edmontosaurus spp., Saurolophus spp., and Prosaurolophus maximus, possibly as a sister-taxon for Kerberosaurus manakini also from the Udurchukan Formation of Far Eastern Russia. The high diversity and mosaic distribution of Maastrichtian hadrosaurid faunas in the Amur-Heilongjiang region are the result of a complex palaeogeographical history and imply that many independent hadrosaurid lineages dispersed without any problem between western America and eastern Asia at the end of the Cretaceous. PMID- 22666330 TI - Retinal axonal loss begins early in the course of multiple sclerosis and is similar between progressive phenotypes. AB - BACKGROUND: To determine whether retinal axonal loss is detectable in patients with a clinically isolated syndrome (CIS), a first clinical demyelinating attack suggestive of multiple sclerosis (MS), and examine patterns of retinal axonal loss across MS disease subtypes. METHODOLOGY/PRINCIPAL FINDINGS: Spectral-domain Optical Coherence Tomography was performed in 541 patients with MS, including 45 with high-risk CIS, 403 with relapsing-remitting (RR)MS, 60 with secondary progressive (SP)MS and 33 with primary-progressive (PP)MS, and 53 unaffected controls. Differences in retinal nerve fiber layer (RNFL) thickness and macular volume were analyzed using multiple linear regression and associations with age and disease duration were examined in a cross-sectional analysis. In eyes without a clinical history of optic neuritis (designated as "eyes without optic neuritis"), the total and temporal peripapillary RNFL was thinner in CIS patients compared to controls (temporal RNFL by -5.4 um [95% CI -0.9 to--9.9 um, p = 0.02] adjusting for age and sex). The total (p = 0.01) and temporal (p = 0.03) RNFL was also thinner in CIS patients with clinical disease for less than 1 year compared to controls. In eyes without optic neuritis, total and temporal RNFL thickness was nearly identical between primary and secondary progressive MS, but total macular volume was slightly lower in the primary progressive group (p<0.05). CONCLUSIONS/SIGNIFICANCE: Retinal axonal loss is increasingly prominent in more advanced stages of disease--progressive MS>RRMS>CIS--with proportionally greater thinning in eyes previously affected by clinically evident optic neuritis. Retinal axonal loss begins early in the course of MS. In the absence of clinically evident optic neuritis, RNFL thinning is nearly identical between progressive MS subtypes. PMID- 22666332 TI - Mentalizing deficits constrain belief in a personal God. AB - Religious believers intuitively conceptualize deities as intentional agents with mental states who anticipate and respond to human beliefs, desires and concerns. It follows that mentalizing deficits, associated with the autistic spectrum and also commonly found in men more than in women, may undermine this intuitive support and reduce belief in a personal God. Autistic adolescents expressed less belief in God than did matched neuro-typical controls (Study 1). In a Canadian student sample (Study 2), and two American national samples that controlled for demographic characteristics and other correlates of autism and religiosity (Study 3 and 4), the autism spectrum predicted reduced belief in God, and mentalizing mediated this relationship. Systemizing (Studies 2 and 3) and two personality dimensions related to religious belief, Conscientiousness and Agreeableness (Study 3), failed as mediators. Mentalizing also explained the robust and well known, but theoretically debated, gender gap in religious belief wherein men show reduced religious belief (Studies 2-4). PMID- 22666333 TI - Limb-bone scaling indicates diverse stance and gait in quadrupedal ornithischian dinosaurs. AB - BACKGROUND: The most primitive ornithischian dinosaurs were small bipeds, but quadrupedality evolved three times independently in the clade. The transition to quadrupedality from bipedal ancestors is rare in the history of terrestrial vertebrate evolution, and extant analogues do not exist. Constraints imposed on quadrupedal ornithischians by their ancestral bipedal bauplan remain unexplored, and consequently, debate continues about their stance and gait. For example, it has been proposed that some ornithischians could run, while others consider that none were cursorial. METHODOLOGY/PRINCIPAL FINDINGS: Drawing on biomechanical concepts of limb bone scaling and locomotor theory developed for extant taxa, we use the largest dataset of ornithischian postcranial measurements so far compiled to examine stance and gait in quadrupedal ornithischians. Differences in femoral midshaft eccentricity in hadrosaurs and ceratopsids may indicate that hadrosaurs placed their feet on the midline during locomotion, while ceratopsids placed their feet more laterally, under the hips. More robust humeri in the largest ceratopsids relative to smaller taxa may be due to positive allometry in skull size with body mass in ceratopsids, while slender humeri in the largest stegosaurs may be the result of differences in dermal armor distribution within the clade. Hadrosaurs are found to display the most cursorial morphologies of the quadrupedal ornithischian cades, indicating higher locomotor performance than in ceratopsids and thyreophorans. CONCLUSIONS/SIGNIFICANCE: Limb bone scaling indicates that a previously unrealised diversity of stances and gaits were employed by quadrupedal ornithischians despite apparent convergence in limb morphology. Grouping quadrupedal ornithischians together as a single functional group hides this disparity. Differences in limb proportions and scaling are likely due to the possession of display structures such as horns, frills and dermal armor that may have affected the center of mass of the animal, and differences in locomotor behaviour such as migration, predator escape or home range size. PMID- 22666334 TI - Tea consumption and incidence of type 2 diabetes in Europe: the EPIC-InterAct case-cohort study. AB - BACKGROUND: In previous meta-analyses, tea consumption has been associated with lower incidence of type 2 diabetes. It is unclear, however, if tea is associated inversely over the entire range of intake. Therefore, we investigated the association between tea consumption and incidence of type 2 diabetes in a European population. METHODOLOGY/PRINCIPAL FINDINGS: The EPIC-InterAct case cohort study was conducted in 26 centers in 8 European countries and consists of a total of 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,835 individuals from a total cohort of 340,234 participants with 3.99 million person-years of follow-up. Country-specific Hazard Ratios (HR) for incidence of type 2 diabetes were obtained after adjustment for lifestyle and dietary factors using a Cox regression adapted for a case-cohort design. Subsequently, country specific HR were combined using a random effects meta-analysis. Tea consumption was studied as categorical variable (0, >0-<1, 1-<4, >= 4 cups/day). The dose response of the association was further explored by restricted cubic spline regression. Country specific medians of tea consumption ranged from 0 cups/day in Spain to 4 cups/day in United Kingdom. Tea consumption was associated inversely with incidence of type 2 diabetes; the HR was 0.84 [95%CI 0.71, 1.00] when participants who drank >= 4 cups of tea per day were compared with non-drinkers (p(linear trend) = 0.04). Incidence of type 2 diabetes already tended to be lower with tea consumption of 1-<4 cups/day (HR = 0.93 [95%CI 0.81, 1.05]). Spline regression did not suggest a non-linear association (p(non-linearity) = 0.20). CONCLUSIONS/SIGNIFICANCE: A linear inverse association was observed between tea consumption and incidence of type 2 diabetes. People who drink at least 4 cups of tea per day may have a 16% lower risk of developing type 2 diabetes than non-tea drinkers. PMID- 22666335 TI - Non-stimulated, agonist-stimulated and store-operated Ca2+ influx in MDA-MB-468 breast cancer cells and the effect of EGF-induced EMT on calcium entry. AB - In addition to their well-defined roles in replenishing depleted endoplasmic reticulum (ER) Ca(2+) reserves, molecular components of the store-operated Ca(2+) entry pathway regulate breast cancer metastasis. A process implicated in cancer metastasis that describes the conversion to a more invasive phenotype is epithelial-mesenchymal transition (EMT). In this study we show that EGF-induced EMT in MDA-MB-468 breast cancer cells is associated with a reduction in agonist stimulated and store-operated Ca(2+) influx, and that MDA-MB-468 cells prior to EMT induction have a high level of non-stimulated Ca(2+) influx. The potential roles for specific Ca(2+) channels in these pathways were assessed by siRNA mediated silencing of ORAI1 and transient receptor potential canonical type 1 (TRPC1) channels in MDA-MB-468 breast cancer cells. Non-stimulated, agonist stimulated and store-operated Ca(2+) influx were significantly inhibited with ORAI1 silencing. TRPC1 knockdown attenuated non-stimulated Ca(2+) influx in a manner dependent on Ca(2+) influx via ORAI1. TRPC1 silencing was also associated with reduced ERK1/2 phosphorylation and changes in the rate of Ca(2+) release from the ER associated with the inhibition of the sarco/endoplasmic reticulum Ca(2+)-ATPase (time to peak [Ca(2+)](CYT) = 188.7 +/- 34.6 s (TRPC1 siRNA) versus 124.0 +/- 9.5 s (non-targeting siRNA); P<0.05). These studies indicate that EMT in MDA-MB-468 breast cancer cells is associated with a pronounced remodeling of Ca(2+) influx, which may be due to altered ORAI1 and/or TRPC1 channel function. Our findings also suggest that TRPC1 channels in MDA-MB-468 cells contribute to ORAI1-mediated Ca(2+) influx in non-stimulated cells. PMID- 22666336 TI - Physiological levels of Pik3ca(H1047R) mutation in the mouse mammary gland results in ductal hyperplasia and formation of ERalpha-positive tumors. AB - PIK3CA, the gene coding for the p110alpha subunit of phosphoinositide 3-kinase, is frequently mutated in a variety of human tumors including breast cancers. To better understand the role of mutant PIK3CA in the initiation and/or progression of breast cancer, we have generated mice with a conditional knock-in of the common activating mutation, Pik3ca(H1047R), into one allele of the endogenous gene in the mammary gland. These mice developed a ductal anaplasia and hyperplasia by 6 weeks of age characterized by multi-layering of the epithelial lining of the mammary ducts and expansion of the luminal progenitor (Lin(-); CD29(lo); CD24(+); CD61(+)) cell population. The Pik3ca(H1047R) expressing mice eventually develop mammary tumors with 100% penetrance but with a long latency (>12 months). This is significantly longer than has been reported for transgenic models where expression of the mutant Pik3ca is driven by an exogenous promoter. Histological analysis of the tumors formed revealed predominantly ERalpha positive fibroadenomas, carcinosarcomas and sarcomas. In vitro induction of Pik3ca(H1047R) in immortalized mammary epithelial cells also resulted in tumor formation when injected into the mammary fat pad of immunodeficient recipient mice. This novel model, which reproduces the scenario of a heterozygous somatic mutation occurring in the endogenous PIK3CA gene, will thus be a valuable tool for investigating the role of Pik3ca(H1047R) mutation in mammary tumorigenesis both in vivo and in vitro. PMID- 22666337 TI - Conserving critical sites for biodiversity provides disproportionate benefits to people. AB - Protecting natural habitats in priority areas is essential to halt the loss of biodiversity. Yet whether these benefits for biodiversity also yield benefits for human well-being remains controversial. Here we assess the potential human well being benefits of safeguarding a global network of sites identified as top priorities for the conservation of threatened species. Conserving these sites would yield benefits--in terms of a) climate change mitigation through avoidance of CO(2) emissions from deforestation; b) freshwater services to downstream human populations; c) retention of option value; and d) benefits to maintenance of human cultural diversity--significantly exceeding those anticipated from randomly selected sites within the same countries and ecoregions. Results suggest that safeguarding sites important for biodiversity conservation provides substantial benefits to human well-being. PMID- 22666338 TI - Second-line antiretroviral therapy in a workplace and community-based treatment programme in South Africa: determinants of virological outcome. AB - BACKGROUND: As antiretroviral treatment (ART) programmes in resource-limited settings mature, more patients are experiencing virological failure. Without resistance testing, deciding who should switch to second-line ART can be difficult. The consequences for second-line outcomes are unclear. In a workplace- and community-based multi-site programme, with 6-monthly virological monitoring, we describe outcomes and predictors of viral suppression on second-line, protease inhibitor-based ART. METHODS: We used prospectively collected clinic data from patients commencing first-line ART between 1/1/03 and 31/12/08 to construct a study cohort of patients switched to second-line ART in the presence of a viral load (VL) >= 400 copies/ml. Predictors of VL<400 copies/ml within 15 months of switch were assessed using modified Poisson regression to estimate risk ratios. RESULTS: 205 workplace patients (91.7% male; median age 43 yrs) and 212 community patients (38.7% male; median age 36 yrs) switched regimens. At switch compared to community patients, workplace patients had a longer duration of viraemia, higher VL, lower CD4 count, and higher reported non-adherence on first-line ART. Non adherence was the reported reason for switching in a higher proportion of workplace patients. Following switch, 48.3% (workplace) and 72.0% (community) achieved VL<400, with non-adherence (17.9% vs. 1.4%) and virological rebound (35.6% vs. 13.2% with available measures) reported more commonly in the workplace programme. In adjusted analysis of the workplace programme, lower switch VL and younger age were associated with VL<400. In the community programme, shorter duration of viraemia, higher CD4 count and transfers into programme on ART were associated with VL<400. CONCLUSION: High levels of viral suppression on second line ART can be, but are not always, achieved in multi-site treatment programmes with both individual- and programme-level factors influencing outcomes. Strategies to support both healthcare workers and patients during this switch period need to be evaluated; sub-optimal adherence, particularly in the workplace programme must be addressed. PMID- 22666339 TI - A tale of many cities: universal patterns in human urban mobility. AB - The advent of geographic online social networks such as Foursquare, where users voluntarily signal their current location, opens the door to powerful studies on human movement. In particular the fine granularity of the location data, with GPS accuracy down to 10 meters, and the worldwide scale of Foursquare adoption are unprecedented. In this paper we study urban mobility patterns of people in several metropolitan cities around the globe by analyzing a large set of Foursquare users. Surprisingly, while there are variations in human movement in different cities, our analysis shows that those are predominantly due to different distributions of places across different urban environments. Moreover, a universal law for human mobility is identified, which isolates as a key component the rank-distance, factoring in the number of places between origin and destination, rather than pure physical distance, as considered in some previous works. Building on our findings, we also show how a rank-based movement model accurately captures real human movements in different cities. PMID- 22666340 TI - Ebi/AP-1 suppresses pro-apoptotic genes expression and permits long-term survival of Drosophila sensory neurons. AB - Sensory organs are constantly exposed to physical and chemical stresses that collectively threaten the survival of sensory neurons. Failure to protect stressed neurons leads to age-related loss of neurons and sensory dysfunction in organs in which the supply of new sensory neurons is limited, such as the human auditory system. Transducin beta-like protein 1 (TBL1) is a candidate gene for ocular albinism with late-onset sensorineural deafness, a form of X-linked age related hearing loss. TBL1 encodes an evolutionarily conserved F-box-like and WD40 repeats-containing subunit of the nuclear receptor co-repressor/silencing mediator for retinoid and thyroid hormone receptor and other transcriptional co repressor complexes. Here we report that a Drosophila homologue of TBL1, Ebi, is required for maintenance of photoreceptor neurons. Loss of ebi function caused late-onset neuronal apoptosis in the retina and increased sensitivity to oxidative stress. Ebi formed a complex with activator protein 1 (AP-1) and was required for repression of Drosophila pro-apoptotic and anti-apoptotic genes expression. These results suggest that Ebi/AP-1 suppresses basal transcription levels of apoptotic genes and thereby protects sensory neurons from degeneration. PMID- 22666341 TI - Multifunctional role of Bcl-2 in malignant transformation and tumorigenesis of Cr(VI)-transformed lung cells. AB - B-cell lymphoma-2 (Bcl-2) is an antiapoptotic protein known to be important in the regulation of apoptosis in various cell types. However, its role in malignant transformation and tumorigenesis of human lung cells is not well understood. We previously reported that chronic exposure of human lung epithelial cells to the carcinogenic hexavalent chromium Cr(VI) caused malignant transformation and Bcl-2 upregulation; however, the role of Bcl-2 in the transformation is unclear. Using a gene silencing approach, we showed that Bcl-2 plays an important role in the malignant properties of Cr(VI)-transformed cells. Downregulation of Bcl-2 inhibited the invasive and proliferative properties of the cells as well as their colony forming and angiogenic activities, which are upregulated in the transformed cells as compared to control cells. Furthermore, animal studies showed the inhibitory effect of Bcl-2 knockdown on the tumorigenesis of Cr(VI) transformed cells. The role of Bcl-2 in malignant transformation and tumorigenesis was confirmed by gene silencing experiments using human lung carcinoma NCI-H460 cells. These cells exhibited aggressive malignant phenotypes similar to those of Cr(VI)-transformed cells. Knockdown of Bcl-2 in the H460 cells inhibited malignant and tumorigenic properties of the cells, indicating the general role of Bcl-2 in human lung tumorigenesis. Ingenuity Pathways Analysis (IPA) revealed potential effectors of Bcl-2 in tumorigenesis regulation. Additionally, using IPA together with ectopic expression of p53, we show p53 as an upstream regulator of Bcl-2 in Cr(VI)-transformed cells. Together, our results indicate the novel and multifunctional role of Bcl-2 in malignant transformation and tumorigenesis of human lung epithelial cells chronically exposed to Cr(VI). PMID- 22666342 TI - Autoimmunity in CD73/Ecto-5'-nucleotidase deficient mice induces renal injury. AB - Extracellular adenosine formed by 5'-ectonucleotidase (CD73) is involved in tubulo-glomerular feedback in the kidney but is also known to be an important immune modulator. Since CD73(-/-)mutant mice exhibit a vascular proinflammatory phenotype, we asked whether long term lack of CD73 causes inflammation related kidney pathologies. CD73(-/-)mice (13 weeks old) showed significantly increased low molecule proteinuria compared to C57BL6 wild type controls (4.8 >= 0.52 vs. 2.9 +/- 0.54 mg/24 h, p<0.03). Total proteinuria increased to 5.97 +/- 0.78 vs. 2.55 +/- 0.35 mg/24 h at 30 weeks (p<0.01) whereas creatinine clearance decreased (0.161 +/- 0.02 vs. 0.224 +/- 0.02 ml/min). We observed autoimmune inflammation in CD73(-/-)mice with glomerulitis and peritubular capillaritis, showing glomerular deposition of IgG and C3 and enhanced presence of CD11b, CD8, CD25 as well as GR-1-positive cells in the interstitium. Vascular inflammation was associated with enhanced serum levels of the cytokines IL-18 and TNF-alpha as well as VEGF and the chemokine MIP-2 (CXCL-2) in CD73(-/-)mice, whereas chemokines and cytokines in the kidney tissue were unaltered or reduced. In CD73( /-)mice glomeruli, we found a reduced number of podocytes and endothelial fenestrations, increased capillaries per glomeruli, endotheliosis and enhanced tubular fibrosis. Our results show that adult CD73(-/-)mice exhibit spontaneous proteinuria and renal functional deterioration even without exogenous stress factors. We have identified an autoimmune inflammatory phenotype comprising the glomerular endothelium, leading to glomeruli inflammation and injury and to a cellular infiltrate of the renal interstitium. Thus, long term lack of CD73 reduced renal function and is associated with autoimmune inflammation. PMID- 22666343 TI - Socioeconomic inequalities in the prevalence of nine established cardiovascular risk factors in a southern European population. AB - The evaluation of the gender-specific prevalence of cardiovascular risk factors across socioeconomic position (SEP) categories may unravel mechanisms involved in the development of coronary heart disease. Using a sample of 1704 community dwellers of a Portuguese urban center aged 40 years or older, assessed in 1999 2003, we quantified the age-standardized prevalence of nine established cardiovascular risk factors (diabetes mellitus, hypertension, hypercholesterolemia, smoking, sedentariness, abdominal obesity, poor diet, excessive alcohol intake and depression) across SEP and gender categories. Data on individual education and occupation were collected by questionnaire and used to characterize SEP. The prevalence of seven out of nine well-established risk factors was higher in men. Among women, the prevalence of most of the studied risk factors was higher in lower SEP groups. The main exception was smoking, which increased with education and occupation levels. Among men, socioeconomic gradients were less clear, but lower SEP was associated with a higher prevalence of diabetes, excessive alcohol intake and depression in a graded mode. The historical cultural beliefs and practices captured throughout the lifecourse frame the wide socioeconomic gradients discernible in our study conducted in an unequal European developed population. While men were more exposed to most risk factors, the clearer associations between SEP and risk factors among women support that their adoption of particular healthy behaviors is more dependent on material and symbolic conditions. To fully address the issue of health inequalities, interventions within the health systems should be complemented with population-based policies specifically designed to reduce socioeconomic gradients. PMID- 22666344 TI - In vivo importance of homologous recombination DNA repair for mouse neural stem and progenitor cells. AB - We characterized the in vivo importance of the homologous recombination factor RAD54 for the developing mouse brain cortex in normal conditions or after ionizing radiation exposure. Contrary to numerous homologous recombination genes, Rad54 disruption did not impact the cortical development without exogenous stress, but it dramatically enhanced the radiation sensitivity of neural stem and progenitor cells. This resulted in the death of all cells irradiated during S or G2, whereas the viability of cells irradiated in G1 or G0 was not affected by Rad54 disruption. Apoptosis occurred after long arrests at intra-S and G2/M checkpoints. This concerned every type of neural stem and progenitor cells, showing that the importance of Rad54 for radiation response was linked to the cell cycle phase at the time of irradiation and not to the differentiation state. In the developing brain, RAD54-dependent homologous recombination appeared absolutely required for the repair of damages induced by ionizing radiation during S and G2 phases, but not for the repair of endogenous damages in normal conditions. Altogether our data support the existence of RAD54-dependent and independent homologous recombination pathways. PMID- 22666345 TI - Transcriptomic characterization of temperature stress responses in larval zebrafish. AB - Temperature influences nearly all biochemical, physiological and life history activities of fish, but the molecular mechanisms underlying the temperature acclimation remains largely unknown. Previous studies have identified many temperature-regulated genes in adult tissues; however, the transcriptional responses of fish larvae to temperature stress are not well understood. In this study, we characterized the transcriptional responses in larval zebrafish exposed to cold or heat stress using microarray analysis. In comparison with genes expressed in the control at 28 degrees C, a total of 2680 genes were found to be affected in 96 hpf larvae exposed to cold (16 degrees C) or heat (34 degrees C) for 2 and 48h and most of these genes were expressed in a temperature-specific and temporally regulated manner. Bioinformatic analysis identified multiple temperature-regulated biological processes and pathways. Biological processes overrepresented among the earliest genes induced by temperature stress include regulation of transcription, nucleosome assembly, chromatin organization and protein folding. However, processes such as RNA processing, cellular metal ion homeostasis and protein transport and were enriched in genes up-regulated under cold exposure for 48 h. Pathways such as mTOR signalling, p53 signalling and circadian rhythm were enriched among cold-induced genes, while adipocytokine signalling, protein export and arginine and praline metabolism were enriched among heat-induced genes. Although most of these biological processes and pathways were specifically regulated by cold or heat, common responses to both cold and heat stresses were also found. Thus, these findings provide new interesting clues for elucidation of mechanisms underlying the temperature acclimation in fish. PMID- 22666346 TI - Dihydroartemisinin enhances Apo2L/TRAIL-mediated apoptosis in pancreatic cancer cells via ROS-mediated up-regulation of death receptor 5. AB - BACKGROUND: Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, has recently shown antitumor activity in various cancer cells. Apo2 ligand or tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) is regarded as a promising anticancer agent, but chemoresistance affects its efficacy as a treatment strategy. Apoptosis induced by the combination of DHA and Apo2L/TRAIL has not been well documented, and the mechanisms involved remain unclear. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report that DHA enhances the efficacy of Apo2L/TRAIL for the treatment of pancreatic cancer. We found that combined therapy using DHA and Apo2L/TRAIL significantly enhanced apoptosis in BxPC-3 and PANC-1 cells compared with single-agent treatment in vitro. The effect of DHA was mediated through the generation of reactive oxygen species, the induction of death receptor 5 (DR5) and the modulation of apoptosis-related proteins. However, N-acetyl cysteine significantly reduced the enhanced apoptosis observed with the combination of DHA and Apo2L/TRAIL. In addition, knockdown of DR5 by small interfering RNA also significantly reduced the amount of apoptosis induced by DHA and Apo2L/TRAIL. CONCLUSIONS/SIGNIFICANCE: These results suggest that DHA enhances Apo2L/TRAIL-mediated apoptosis in human pancreatic cancer cells through reactive oxygen species-mediated up-regulation of DR5. PMID- 22666347 TI - Isolation and characterisation of a human-like antibody fragment (scFv) that inactivates VEEV in vitro and in vivo. AB - Venezuelan equine encephalitis virus (VEEV) belongs to the Alphavirus genus and several species of this family are pathogenic to humans. The viruses are classified as potential agents of biological warfare and terrorism and sensitive detection as well as effective prophylaxis and antiviral therapies are required.In this work, we describe the isolation of the anti-VEEV single chain Fragment variable (scFv), ToR67-3B4, from a non-human primate (NHP) antibody gene library. We report its recloning into the bivalent scFv-Fc format and further immunological and biochemical characterisation.The scFv-Fc ToR67-3B4 recognised viable as well as formalin and beta-propionolactone (beta-Pl) inactivated virus particles and could be applied for immunoblot analysis of VEEV proteins and immuno-histochemistry of VEEV infected cells. It detected specifically the viral E1 envelope protein of VEEV but did not react with reduced viral glycoprotein preparations suggesting that recognition depends upon conformational epitopes. The recombinant antibody was able to detect multiple VEEV subtypes and displayed only marginal cross-reactivity to other Alphavirus species except for EEEV. In addition, the scFv-Fc fusion described here might be of therapeutic use since it successfully inactivated VEEV in a murine disease model. When the recombinant antibody was administered 6 hours post challenge, 80% to 100% of mice survived lethal VEEV IA/B or IE infection. Forty to sixty percent of mice survived when scFv-Fc ToR67-3B4 was applied 6 hours post challenge with VEEV subtypes II and former IIIA. In combination with E2-neutralising antibodies the NHP antibody isolated here could significantly improve passive protection as well as generic therapy of VEE. PMID- 22666348 TI - An individual-oriented model on the emergence of support in fights, its reciprocation and exchange. AB - Complex social behaviour of primates has usually been attributed to the operation of complex cognition. Recently, models have shown that constraints imposed by the socio-spatial structuring of individuals in a group may result in an unexpectedly high number of patterns of complex social behaviour, resembling the dominance styles of egalitarian and despotic species of macaques and the differences between them. This includes affiliative patterns, such as reciprocation of grooming, grooming up the hierarchy, and reconciliation. In the present study, we show that the distribution of support in fights, which is the social behaviour that is potentially most sophisticated in terms of cognitive processes, may emerge in the same way. The model represents the spatial grouping of individuals and their social behaviour, such as their avoidance of risks during attacks, the self-reinforcing effects of winning and losing their fights, their tendency to join in fights of others that are close by (social facilitation), their tendency to groom when they are anxious, the reduction of their anxiety by grooming, and the increase of anxiety when involved in aggression. Further, we represent the difference in intensity of aggression apparent in egalitarian and despotic macaques. The model reproduces many aspects of support in fights, such as its different types, namely, conservative, bridging and revolutionary, patterns of choice of coalition partners attributed to triadic awareness, those of reciprocation of support and 'spiteful acts' and of exchange between support and grooming. This work is important because it suggests that behaviour that seems to result from sophisticated cognition may be a side-effect of spatial structure and dominance interactions and it shows that partial correlations fail to completely omit these effects of spatial structure. Further, the model is falsifiable, since it results in many patterns that can easily be tested in real primates by means of existing data. PMID- 22666349 TI - Towards operational modeling and forecasting of the Iberian shelves ecosystem. AB - There is a growing interest on physical and biogeochemical oceanic hindcasts and forecasts from a wide range of users and businesses. In this contribution we present an operational biogeochemical forecast system for the Portuguese and Galician oceanographic regions, where atmospheric, hydrodynamic and biogeochemical variables are integrated. The ocean model ROMS, with a horizontal resolution of 3 km, is forced by the atmospheric model WRF and includes a Nutrients-Phytoplankton-Zooplankton-Detritus biogeochemical module (NPZD). In addition to oceanographic variables, the system predicts the concentration of nitrate, phytoplankton, zooplankton and detritus (mmol N m(-3)). Model results are compared against radar currents and remote sensed SST and chlorophyll. Quantitative skill assessment during a summer upwelling period shows that our modelling system adequately represents the surface circulation over the shelf including the observed spatial variability and trends of temperature and chlorophyll concentration. Additionally, the skill assessment also shows some deficiencies like the overestimation of upwelling circulation and consequently, of the duration and intensity of the phytoplankton blooms. These and other departures from the observations are discussed, their origins identified and future improvements suggested. The forecast system is the first of its kind in the region and provides free online distribution of model input and output, as well as comparisons of model results with satellite imagery for qualitative operational assessment of model skill. PMID- 22666350 TI - Evaluation of a rapid test for the diagnosis of cholera in the absence of a gold standard. AB - BACKGROUND: Early detection and confirmation of cholera outbreaks are crucial for rapid implementation of control measures. Because cholera frequently affects regions with limited laboratory resources, rapid diagnostic tests (RDT) designed for field conditions are important to enhance rapid response. Stool culture remains the "gold standard" for cholera diagnosis; however, its lack of sensitivity may lead to underestimation of test specificity. We evaluated the Crystal VC(r) immunochromatographic test (Span Diagnostics, India) for cholera diagnosis using a modified reference standard that combines culture-dependent and independent assays, or a Bayesian latent class model (LCM) analysis. METHODOLOGY/PRINCIPAL FINDINGS: The study was conducted during a cholera epidemic in 2008, in Lubumbashi, Democratic Republic of Congo. Stools collected from 296 patients were used to perform the RDT on site and sent to Institut Pasteur, Paris, for bacterial culture. In comparison with culture as the gold standard, the RDT showed good sensitivity (92.2%; 95% CI: 86.8%-95.9%) but poor specificity when used by a trained laboratory technician (70.6%; 95% CI: 60.7%-79.2%) or by clinicians with no specific test training (60.4%, 95% CI: 50.2%-70.0%). The specificity of the test performed by the laboratory technician increased to 88.6% (95% CI: 78.7-94.9) when PCR was combined with culture results as the reference standard, and to 85.0% (95% CI: 70.4-99.2), when the Bayesian LCM analysis was used for performance evaluation. In both cases, the sensitivity remained high. CONCLUSION: Using an improved reference standard or appropriate statistical methods for diagnostic test evaluations in the absence of a gold standard, we report better performance of the Crystal VC(r) RDT than previously published. Our results confirm that this test can be used for early outbreak detection or epidemiological surveillance, key components of efficient global cholera control. Our analysis also highlights the importance of improving evaluations of RDT when no reliable gold standard is available. PMID- 22666352 TI - Artificial polyploidy improves bacterial single cell genome recovery. AB - BACKGROUND: Single cell genomics (SCG) is a combination of methods whose goal is to decipher the complete genomic sequence from a single cell and has been applied mostly to organisms with smaller genomes, such as bacteria and archaea. Prior single cell studies showed that a significant portion of a genome could be obtained. However, breakages of genomic DNA and amplification bias have made it very challenging to acquire a complete genome with single cells. We investigated an artificial method to induce polyploidy in Bacillus subtilis ATCC 6633 by blocking cell division and have shown that we can significantly improve the performance of genomic sequencing from a single cell. METHODOLOGY/PRINCIPAL FINDINGS: We inhibited the bacterial cytoskeleton protein FtsZ in B.subtilis with an FtsZ-inhibiting compound, PC190723, resulting in larger undivided single cells with multiple copies of its genome. qPCR assays of these larger, sorted cells showed higher DNA content, have less amplification bias, and greater genomic recovery than untreated cells. SIGNIFICANCE: The method presented here shows the potential to obtain a nearly complete genome sequence from a single bacterial cell. With millions of uncultured bacterial species in nature, this method holds tremendous promise to provide insight into the genomic novelty of yet-to-be discovered species, and given the temporary effects of artificial polyploidy coupled with the ability to sort and distinguish differences in cell size and genomic DNA content, may allow recovery of specific organisms in addition to their genomes. PMID- 22666351 TI - Influence of neonatal hypothyroidism on hepatic gene expression and lipid metabolism in adulthood. AB - Thyroid hormones are required for normal growth and development in mammals. Congenital-neonatal hypothyroidism (CH) has a profound impact on physiology, but its specific influence in liver is less understood. Here, we studied how CH influences the liver gene expression program in adulthood. Pregnant rats were given the antithyroid drug methimazole (MMI) from GD12 until PND30 to induce CH in male offspring. Growth defects due to CH were evident as reductions in body weight and tail length from the second week of life. Once the MMI treatment was discontinued, the feed efficiency increased in CH, and this was accompanied by significant catch-up growth. On PND80, significant reductions in body mass, tail length, and circulating IGF-I levels remained in CH rats. Conversely, the mRNA levels of known GH target genes were significantly upregulated. The serum levels of thyroid hormones, cholesterol, and triglycerides showed no significant differences. In contrast, CH rats showed significant changes in the expression of hepatic genes involved in lipid metabolism, including an increased transcription of PPARalpha and a reduced expression of genes involved in fatty acid and cholesterol uptake, cellular sterol efflux, triglyceride assembly, bile acid synthesis, and lipogenesis. These changes were associated with a decrease of intrahepatic lipids. Finally, CH rats responded to the onset of hypothyroidism in adulthood with a reduction of serum fatty acids and hepatic cholesteryl esters and to T3 replacement with an enhanced activation of malic enzyme. In summary, we provide in vivo evidence that neonatal hypothyroidism influences the hepatic transcriptional program and tissue sensitivity to hormone treatment in adulthood. This highlights the critical role that a euthyroid state during development plays on normal liver physiology in adulthood. PMID- 22666353 TI - ATP-sensitive potassium channels exhibit variance in the number of open channels below the limit predicted for identical and independent gating. AB - In small cells containing small numbers of ion channels, noise due to stochastic channel opening and closing can introduce a substantial level of variability into the cell's membrane potential. Negatively cooperative interactions that couple a channel's gating conformational change to the conformation of its neighbor(s) provide a potential mechanism for mitigating this variability, but such interactions have not previously been directly observed. Here we show that heterologously expressed ATP-sensitive potassium channels generate noise (i.e., variance in the number of open channels) below the level possible for identical and independent channels. Kinetic analysis with single-molecule resolution supports the interpretation that interchannel negative cooperativity (specifically, the presence of an open channel making a closed channel less likely to open) contributes to the decrease in noise. Functional coupling between channels may be important in modulating stochastic fluctuations in cellular signaling pathways. PMID- 22666354 TI - Stable isotope tracking of endangered sea turtles: validation with satellite telemetry and delta15N analysis of amino acids. AB - Effective conservation strategies for highly migratory species must incorporate information about long-distance movements and locations of high-use foraging areas. However, the inherent challenges of directly monitoring these factors call for creative research approaches and innovative application of existing tools. Highly migratory marine species, such as marine turtles, regularly travel hundreds or thousands of kilometers between breeding and feeding areas, but identification of migratory routes and habitat use patterns remains elusive. Here we use satellite telemetry in combination with compound-specific isotope analysis of amino acids to confirm that insights from bulk tissue stable isotope analysis can reveal divergent migratory strategies and within-population segregation of foraging groups of critically endangered leatherback sea turtles (Dermochelys coriacea) across the Pacific Ocean. Among the 78 turtles studied, we found a distinct dichotomy in delta(15)N values of bulk skin, with distinct "low delta(15)N" and "high delta(15)N" groups. delta(15)N analysis of amino acids confirmed that this disparity resulted from isotopic differences at the base of the food chain and not from differences in trophic position between the two groups. Satellite tracking of 13 individuals indicated that their bulk skin delta(15)N value was linked to the particular foraging region of each turtle. These findings confirm that prevailing marine isoscapes of foraging areas can be reflected in the isotopic compositions of marine turtle body tissues sampled at nesting beaches. We use a Bayesian mixture model to show that between 82 and 100% of the 78 skin-sampled turtles could be assigned with confidence to either the eastern Pacific or western Pacific, with 33 to 66% of all turtles foraging in the eastern Pacific. Our forensic approach validates the use of stable isotopes to depict leatherback turtle movements over broad spatial ranges and is timely for establishing wise conservation efforts in light of this species' imminent risk of extinction in the Pacific. PMID- 22666355 TI - Metamorphosis in the cirripede crustacean Balanus amphitrite. AB - Stalked and acorn barnacles (Cirripedia Thoracica) have a complex life cycle that includes a free-swimming nauplius larva, a cypris larva and a permanently attached sessile juvenile and adult barnacle. The barnacle cyprid is among the most highly specialized of marine invertebrate larvae and its settlement biology has been intensively studied. By contrast, surprisingly few papers have dealt with the critical series of metamorphic events from cementation of the cyprid to the substratum until the appearance of a suspension feeding juvenile. This metamorphosis is both ontogenetically complex and critical to the survival of the barnacle. Here we use video microscopy to present a timeline and description of morphological events from settled cyprid to juvenile barnacle in the model species Balanus amphitrite, representing an important step towards both a broader understanding of the settlement ecology of this species and a platform for studying the factors that control its metamorphosis. Metamorphosis in B. amphitrite involves a complex sequence of events: cementation, epidermis separation from the cypris cuticle, degeneration of cypris musculature, rotation of the thorax inside the mantle cavity, building of the juvenile musculature, contraction of antennular muscles, raising of the body, shedding of the cypris cuticle, shell plate and basis formation and, possibly, a further moult to become a suspension feeding barnacle. We compare these events with developmental information from other barnacle species and discuss them in the framework of barnacle settlement ecology. PMID- 22666356 TI - Citrulline a more suitable substrate than arginine to restore NO production and the microcirculation during endotoxemia. AB - BACKGROUND: Impaired microcirculation during endotoxemia correlates with a disturbed arginine-nitric oxide (NO) metabolism and is associated with deteriorating organ function. Improving the organ perfusion in endotoxemia, as often seen in patients with severe infection or systemic inflammatory response syndrome (SIRS) is, therefore, an important therapeutic target. We hypothesized that supplementation of the arginine precursor citrulline rather than arginine would specifically increase eNOS-induced intracellular NO production and thereby improve the microcirculation during endotoxemia. METHODOLOGY/PRINCIPAL FINDINGS: To study the effects of L-Citrulline and L-Arginine supplementation on jejunal microcirculation, intracellular arginine availability and NO production in a non lethal prolonged endotoxemia model in mice. C57/Bl6 mice received an 18 hrs intravenous infusion of endotoxin (LPS, 0.4 ug * g bodyweight(-1) * h(-1)), combined with either L-Citrulline (6.25 mg * h-1), L-Arginine (6.25 mg * h(-1)), or L-Alanine (isonitrogenous control; 12.5 mg * h(-1)) during the last 6 hrs. The control group received an 18 hrs sterile saline infusion combined with L-Alanine or L-Citrulline during the last 6 hrs. The microcirculation was evaluated at the end of the infusion period using sidestream dark-field imaging of jejunal villi. Plasma and jejunal tissue amino-acid concentrations were measured by HPLC, NO tissue concentrations by electron-spin resonance spectroscopy and NOS protein concentrations using Western blot. CONCLUSION/SIGNIFICANCE: L-Citrulline supplementation during endotoxemia positively influenced the intestinal microvascular perfusion compared to L-Arginine-supplemented and control endotoxemic mice. L-Citrulline supplementation increased plasma and tissue concentrations of arginine and citrulline, and restored intracellular NO production in the intestine. L-Arginine supplementation did not increase the intracellular arginine availability. Jejunal tissues in the L-Citrulline supplemented group showed, compared to the endotoxemic and L-Arginine supplemented endotoxemic group, an increase in degree of phosphorylation of eNOS (Ser 1177) and a decrease in iNOS protein level. In conclusion, L-Citrulline supplementation during endotoxemia and not L-Arginine reduced intestinal microcirculatory dysfunction and increased intracellular NO production, likely via increased intracellular citrulline and arginine availability. PMID- 22666357 TI - Antiretroviral simplification with darunavir/ritonavir monotherapy in routine clinical practice: safety, effectiveness, and impact on lipid profile. AB - BACKGROUND: Simplification of antiretroviral treatment (ART) with darunavir/ritonavir (DRV/r) monotherapy has achieved sustained suppression of plasma viral load (pVL) in clinical trials; however, its effectiveness and safety profile has not been evaluated in routine clinical practice. METHODOLOGY/PRINCIPAL FINDINGS: We performed a retrospective cohort analysis of HIV-1-infected patients who initiated DRV/r monotherapy once daily with a pVL <50 copies/mL under ART and at least 1 subsequent follow-up visit in our clinic. The primary study endpoints were the percentage of patients with virological failure (VF, defined as 2 consecutive pVL>50 copies/mL) at week 48, and time to VF. Other causes of treatment discontinuation and changes in lipid profile were evaluated up to week 48. Ninety-two patients were followed for a median (IQR) of 73 (57-92) weeks. The median baseline and nadir CD4+ T-cell counts were 604 (433-837) and 238 (150-376) cells/mm3, respectively. Patients had previously received a median of 5 (3-9) ART lines and maintained a pVL<50 copies/mL for a median of 76 (32 176) weeks before initiating DRV/r monotherapy. Nine (9.8%) patients developed VF at week 48; time to VF was 47.1 (IQR: 36.1-47.8) weeks among patients with VF. Other reasons for changing ART were gastrointestinal disturbances (n = 3), rash (n = 1), and impaired CD4 recovery (n = 2). Median low-density lipoprotein cholesterol levels increased from 116.1 mg/dL at baseline to 137.3 mg/dL at 48 weeks (p = 0.001). CONCLUSIONS/SIGNIFICANCE: Treatment simplification with DRV/r monotherapy seems safe and effective in routine clinical practice. Further research is needed to elucidate the effect of DRV/r monotherapy on cholesterol levels. PMID- 22666358 TI - Microtubule destabilization is shared by genetic and idiopathic Parkinson's disease patient fibroblasts. AB - Data from both toxin-based and gene-based models suggest that dysfunction of the microtubule system contributes to the pathogenesis of Parkinson's disease, even if, at present, no evidence of alterations of microtubules in vivo or in patients is available. Here we analyze cytoskeleton organization in primary fibroblasts deriving from patients with idiopathic or genetic Parkinson's disease, focusing on mutations in parkin and leucine-rich repeat kinase 2. Our analyses reveal that genetic and likely idiopathic pathology affects cytoskeletal organization and stability, without any activation of autophagy or apoptosis. All parkinsonian fibroblasts have a reduced microtubule mass, represented by a higher fraction of unpolymerized tubulin in respect to control cells, and display significant changes in microtubule stability-related signaling pathways. Furthermore, we show that the reduction of microtubule mass is so closely related to the alteration of cell morphology and behavior that both pharmacological treatment with microtubule targeted drugs, and genetic approaches, by transfecting the wild type parkin or leucine-rich repeat kinase 2, restore the proper microtubule stability and are able to rescue cell architecture. Taken together, our results suggest that microtubule destabilization is a point of convergence of genetic and idiopathic forms of parkinsonism and highlight, for the first time, that microtubule dysfunction occurs in patients and not only in experimental models of Parkinson's disease. Therefore, these data contribute to the knowledge on molecular and cellular events underlying Parkinson's disease and, revealing that correction of microtubule defects restores control phenotype, may offer a new therapeutic target for the management of the disease. PMID- 22666359 TI - Timescales of quartz crystallization and the longevity of the Bishop giant magma body. AB - Supereruptions violently transfer huge amounts (100 s-1000 s km(3)) of magma to the surface in a matter of days and testify to the existence of giant pools of magma at depth. The longevity of these giant magma bodies is of significant scientific and societal interest. Radiometric data on whole rocks, glasses, feldspar and zircon crystals have been used to suggest that the Bishop Tuff giant magma body, which erupted ~760,000 years ago and created the Long Valley caldera (California), was long-lived (>100,000 years) and evolved rather slowly. In this work, we present four lines of evidence to constrain the timescales of crystallization of the Bishop magma body: (1) quartz residence times based on diffusional relaxation of Ti profiles, (2) quartz residence times based on the kinetics of faceting of melt inclusions, (3) quartz and feldspar crystallization times derived using quartz+feldspar crystal size distributions, and (4) timescales of cooling and crystallization based on thermodynamic and heat flow modeling. All of our estimates suggest quartz crystallization on timescales of <10,000 years, more typically within 500-3,000 years before eruption. We conclude that large-volume, crystal-poor magma bodies are ephemeral features that, once established, evolve on millennial timescales. We also suggest that zircon crystals, rather than recording the timescales of crystallization of a large pool of crystal-poor magma, record the extended periods of time necessary for maturation of the crust and establishment of these giant magma bodies. PMID- 22666360 TI - Age-specific characteristics and coupling of cerebral arterial inflow and cerebrospinal fluid dynamics. AB - The objective of this work is to quantify age-related differences in the characteristics and coupling of cerebral arterial inflow and cerebrospinal fluid (CSF) dynamics. To this end, 3T phase-contrast magnetic resonance imaging blood and CSF flow data of eleven young (24 +/- 3 years) and eleven elderly subjects (70 +/- 5 years) with a comparable sex-ratio were acquired. Flow waveforms and their frequency composition, transfer functions from blood to CSF flows and cross correlations were analyzed. The magnitudes of the frequency components of CSF flow in the aqueduct differ significantly between the two age groups, as do the frequency components of the cervical spinal CSF and the arterial flows. The males' aqueductal CSF stroke volumes and average flow rates are significantly higher than those of the females. Transfer functions and cross-correlations between arterial blood and CSF flow reveal significant age-dependence of phase shift between these, as do the waveforms of arterial blood, as well as cervical spinal and aqueductal CSF flows. These findings accentuate the need for age- and sex-matched control groups for the evaluation of cerebral pathologies such as hydrocephalus. PMID- 22666361 TI - Spatial correlations in attribute communities. AB - Community detection is an important tool for exploring and classifying the properties of large complex networks and should be of great help for spatial networks. Indeed, in addition to their location, nodes in spatial networks can have attributes such as the language for individuals, or any other socio economical feature that we would like to identify in communities. We discuss in this paper a crucial aspect which was not considered in previous studies which is the possible existence of correlations between space and attributes. Introducing a simple toy model in which both space and node attributes are considered, we discuss the effect of space-attribute correlations on the results of various community detection methods proposed for spatial networks in this paper and in previous studies. When space is irrelevant, our model is equivalent to the stochastic block model which has been shown to display a detectability-non detectability transition. In the regime where space dominates the link formation process, most methods can fail to recover the communities, an effect which is particularly marked when space-attributes correlations are strong. In this latter case, community detection methods which remove the spatial component of the network can miss a large part of the community structure and can lead to incorrect results. PMID- 22666362 TI - Integrative taxonomy for continental-scale terrestrial insect observations. AB - Although 21(st) century ecology uses unprecedented technology at the largest spatio-temporal scales in history, the data remain reliant on sound taxonomic practices that derive from 18(th) century science. The importance of accurate species identifications has been assessed repeatedly and in instances where inappropriate assignments have been made there have been costly consequences. The National Ecological Observatory Network (NEON) will use a standardized system based upon an integrative taxonomic foundation to conduct observations of the focal terrestrial insect taxa, ground beetles and mosquitoes, at the continental scale for a 30 year monitoring program. The use of molecular data for continental scale, multi-decadal research conducted by a geographically widely distributed set of researchers has not been evaluated until this point. The current paper addresses the development of a reference library for verifying species identifications at NEON and the key ways in which this resource will enhance a variety of user communities. PMID- 22666363 TI - Measuring changes in consumer resource availability to riverine pulsing in Breton Sound, Louisiana, USA. AB - Resource pulses are thought to structure communities and food webs through the assembly of consumers. Aggregated consumers represent a high quality resource subsidy that becomes available for trophic transfer during and after the pulse. In estuarine systems, riverine flood pulses deliver large quantities of basal resources and make high quality habitat available for exploitation by consumers. These consumers represent a change in resources that may be available for trophic transfer. We quantified this increased consumer resource availability (nekton density, biomass, energy density) provided by riverine flood pulsing in Breton Sound, Louisiana, USA. We used water level differences between an area subject to two experimental riverine flood pulses (inflow) and a reference area not receiving inflow to identify the percentage of nekton standing stock and energy density that may be attributable solely to riverine pulsing and may represent a consumer resource subsidy. Riverine pulsing accounted for more than 60% of resident nekton density (ind m(-2)), biomass (g m(-2)), and energy density (cal m(-2)) on the flooded marsh surface during two experimental pulse events in 2005. Our results document the potential subsidy of resident nekton standing stock from a riverine flood pulse available for export to subtidal habitats. Given predicted large scale changes in river discharge globally, this approach could provide a useful tool for quantifying the effects of changes in riverine discharge on consumer resource availability. PMID- 22666364 TI - Chronic alcohol exposure alters behavioral and synaptic plasticity of the rodent prefrontal cortex. AB - In the present study, we used a mouse model of chronic intermittent ethanol (CIE) exposure to examine how CIE alters the plasticity of the medial prefrontal cortex (mPFC). In acute slices obtained either immediately or 1-week after the last episode of alcohol exposure, voltage-clamp recording of excitatory post-synaptic currents (EPSCs) in mPFC layer V pyramidal neurons revealed that CIE exposure resulted in an increase in the NMDA/AMPA current ratio. This increase appeared to result from a selective increase in the NMDA component of the EPSC. Consistent with this, Western blot analysis of the postsynaptic density fraction showed that while there was no change in expression of the AMPA GluR1 subunit, NMDA NR1 and NRB subunits were significantly increased in CIE exposed mice when examined immediately after the last episode of alcohol exposure. Unexpectedly, this increase in NR1 and NR2B was no longer observed after 1-week of withdrawal in spite of a persistent increase in synaptic NMDA currents. Analysis of spines on the basal dendrites of layer V neurons revealed that while the total density of spines was not altered, there was a selective increase in the density of mushroom type spines following CIE exposure. Examination of NMDA-receptor mediated spike timing-dependent plasticity (STDP) showed that CIE exposure was associated with altered expression of long-term potentiation (LTP). Lastly, behavioral studies using an attentional set-shifting task that depends upon the mPFC for optimal performance revealed deficits in cognitive flexibility in CIE exposed mice when tested up to 1-week after the last episode of alcohol exposure. Taken together, these observations are consistent with those in human alcoholics showing protracted deficits in executive function, and suggest these deficits may be associated with alterations in synaptic plasticity in the mPFC. PMID- 22666365 TI - Intranasal "painless" human Nerve Growth Factor [corrected] slows amyloid neurodegeneration and prevents memory deficits in App X PS1 mice. AB - Nerve Growth Factor (NGF) is being considered as a therapeutic candidate for Alzheimer's disease (AD) treatment but the clinical application is hindered by its potent pro-nociceptive activity. Thus, to reduce systemic exposure that would induce pain, in recent clinical studies NGF was administered through an invasive intracerebral gene-therapy approach. Our group demonstrated the feasibility of a non-invasive intranasal delivery of NGF in a mouse model of neurodegeneration. NGF therapeutic window could be further increased if its nociceptive effects could be avoided altogether. In this study we exploit forms of NGF, mutated at residue R100, inspired by the human genetic disease HSAN V (Hereditary Sensory Autonomic Neuropathy Type V), which would allow increasing the dose of NGF without triggering pain. We show that "painless" hNGF displays full neurotrophic and anti-amyloidogenic activities in neuronal cultures, and a reduced nociceptive activity in vivo. When administered intranasally to APPxPS1 mice ( n = 8), hNGFP61S/R100E prevents the progress of neurodegeneration and of behavioral deficits. These results demonstrate the in vivo neuroprotective and anti amyloidogenic properties of hNGFR100 mutants and provide a rational basis for the development of "painless" hNGF variants as a new generation of therapeutics for neurodegenerative diseases. PMID- 22666366 TI - White matter abnormalities in major depression: a tract-based spatial statistics and rumination study. AB - Increasing evidence indicates that major depressive disorder (MDD) is usually accompanied by altered white matter in the prefrontal cortex, the parietal lobe and the limbic system. As a behavioral abnormity of MDD, rumination has been believed to be a substantial indicator of the mental state of the depressive state. So far, however, no report that we are aware of has evaluated the relationship between white matter alterations and the ruminative state. In this study, we first explored the altered white matter using a tract-based spatial statistics (TBSS) method based on diffusion tensor imaging of 19 healthy and 16 depressive subjects. We then investigated correlations between the altered white matter microstructure in the identified altered regions and the severity of ruminations measured by the ruminative response scale. Our results demonstrated altered white matter microstructure in circuits connecting the prefrontal lobe, the parietal lobe and the limbic system (p<0.005, uncorrected), findings which support previous research. More importantly, the result also indicated that a greater alteration in the white matter is associated with a more ruminative state (p<0.05, Bonferroni corrected). The detected abnormalities in the white matter should be interpreted cautiously because of the small sample size in this study. This finding supports the psychometric significance of white matter deficits in MDD. PMID- 22666367 TI - Sarcopenia predicts early dose-limiting toxicities and pharmacokinetics of sorafenib in patients with hepatocellular carcinoma. AB - BACKGROUND: Sorafenib induces frequent dose limiting toxicities (DLT) in patients with advanced hepatocellular carcinoma (HCC). Sarcopenia has been associated with poor performance status and shortened survival in cancer patients. PATIENTS AND METHODS: The characteristics of Child Pugh A cirrhotic patients with HCC receiving sorafenib in our institution were retrospectively analyzed. Sorafenib plasma concentrations were determined at each visit. Toxicities were recorded during the first month of treatment, and sarcopenia was determined from baseline CT-scans. RESULTS: Forty patients (30 males) were included. Eleven (27.5%) were sarcopenic. Eighteen patients (45%) experienced a DLT during the first month of treatment. Sarcopenic patients experienced significantly more DLTs than non sarcopenic patients did (82% versus 31%, p = 0.005). Grade 3 diarrhea was significantly more frequent in sarcopenic patients than in non-sarcopenic patients (45.5% versus 6.9%, p = 0.01), but not grade 3 hand foot syndrome reaction (9% versus 17.2%, p = 1). On day 28, median sorafenib AUC (n = 17) was significantly higher in sarcopenic patients (102.4 mg/l.h versus 53.7 mg/l.h, p = 0.013). CONCLUSIONS: Among cirrhotic Child Pugh A patients with advanced HCC, sarcopenia predicts sorafenib exposure and the occurrence of DLT within the first month of treatment. PMID- 22666368 TI - MALDI-TOF MS enables the rapid identification of the major molecular types within the Cryptococcus neoformans/C. gattii species complex. AB - BACKGROUND: The Cryptococcus neoformans/C. gattii species complex comprises two sibling species that are divided into eight major molecular types, C. neoformans VNI to VNIV and C. gattii VGI to VGIV. These genotypes differ in host range, epidemiology, virulence, antifungal susceptibility and geographic distribution. The currently used phenotypic and molecular identification methods for the species/molecular types are time consuming and expensive. As Matrix-Assisted Laser Desorption Ionization-Time-of-Flight Mass Spectrometry (MALDI-TOF MS) offers an effective alternative for the rapid identification of microorganisms, the objective of this study was to examine its potential for the identification of C. neoformans and C. gattii strains at the intra- and inter-species level. METHODOLOGY: Protein extracts obtained via the formic acid extraction method of 164 C. neoformans/C. gattii isolates, including four inter-species hybrids, were studied. RESULTS: The obtained mass spectra correctly identified 100% of all studied isolates, grouped each isolate according to the currently recognized species, C. neoformans and C. gattii, and detected potential hybrids. In addition, all isolates were clearly separated according to their major molecular type, generating greater spectral differences among the C. neoformans molecular types than the C. gattii molecular types, most likely reflecting a closer phylogenetic relationship between the latter. The number of colonies used and the incubation length did not affect the results. No spectra were obtained from intact yeast cells. An extended validated spectral library containing spectra of all eight major molecular types was established. CONCLUSIONS: MALDI-TOF MS is a rapid identification tool for the correct recognition of the two currently recognized human pathogenic Cryptococcus species and offers a simple method for the separation of the eight major molecular types and the detection of hybrid strains within this species complex in the clinical laboratory. The obtained mass spectra provide further evidence that the major molecular types warrant variety or even species status. PMID- 22666369 TI - Crosstalk between mitochondrial and sarcoplasmic reticulum Ca2+ cycling modulates cardiac pacemaker cell automaticity. AB - BACKGROUND: Mitochondria dynamically buffer cytosolic Ca(2+) in cardiac ventricular cells and this affects the Ca(2+) load of the sarcoplasmic reticulum (SR). In sinoatrial-node cells (SANC) the SR generates periodic local, subsarcolemmal Ca(2+) releases (LCRs) that depend upon the SR load and are involved in SANC automaticity: LCRs activate an inward Na(+)-Ca(2+) exchange current to accelerate the diastolic depolarization, prompting the ensemble of surface membrane ion channels to generate the next action potential (AP). OBJECTIVE: To determine if mitochondrial Ca(2+) (Ca(2+) (m)), cytosolic Ca(2+) (Ca(2+) (c))-SR-Ca(2+) crosstalk occurs in single rabbit SANC, and how this may relate to SANC normal automaticity. RESULTS: Inhibition of mitochondrial Ca(2+) influx into (Ru360) or Ca(2+) efflux from (CGP-37157) decreased [Ca(2+)](m) to 80 +/- 8% control or increased [Ca(2+)](m) to 119 +/- 7% control, respectively. Concurrent with inhibition of mitochondrial Ca(2+) influx or efflux, the SR Ca(2+) load, and LCR size, duration, amplitude and period (imaged via confocal linescan) significantly increased or decreased, respectively. Changes in total ensemble LCR Ca(2+) signal were highly correlated with the change in the SR Ca(2+) load (r(2) = 0.97). Changes in the spontaneous AP cycle length (Ru360, 111 +/- 1% control; CGP-37157, 89 +/- 2% control) in response to changes in [Ca(2+)](m) were predicted by concurrent changes in LCR period (r(2) = 0.84). CONCLUSION: A change in SANC Ca(2+) (m) flux translates into a change in the AP firing rate by effecting changes in Ca(2+) (c) and SR Ca(2+) loading, which affects the characteristics of spontaneous SR Ca(2+) release. PMID- 22666370 TI - Gene repertoire evolution of Streptococcus pyogenes inferred from phylogenomic analysis with Streptococcus canis and Streptococcus dysgalactiae. AB - Streptococcus pyogenes, is an important human pathogen classified within the pyogenic group of streptococci, exclusively adapted to the human host. Our goal was to employ a comparative evolutionary approach to better understand the genomic events concomitant with S. pyogenes human adaptation. As part of ascertaining these events, we sequenced the genome of one of the potential sister species, the agricultural pathogen S. canis, and combined it in a comparative genomics reconciliation analysis with two other closely related species, Streptococcus dysgalactiae and Streptococcus equi, to determine the genes that were gained and lost during S. pyogenes evolution. Genome wide phylogenetic analyses involving 15 Streptococcus species provided convincing support for a clade of S. equi, S. pyogenes, S. dysgalactiae, and S. canis and suggested that the most likely S. pyogenes sister species was S. dysgalactiae. The reconciliation analysis identified 113 genes that were gained on the lineage leading to S. pyogenes. Almost half (46%) of these gained genes were phage associated and 14 showed significant matches to experimentally verified bacteria virulence factors. Subsequent to the origin of S. pyogenes, over half of the phage associated genes were involved in 90 different LGT events, mostly involving different strains of S. pyogenes, but with a high proportion involving the horse specific pathogen S. equi subsp. equi, with the directionality almost exclusively (86%) in the S. pyogenes to S. equi direction. Streptococcus agalactiae appears to have played an important role in the evolution of S. pyogenes with a high proportion of LGTs originating from this species. Overall the analysis suggests that S. pyogenes adaptation to the human host was achieved in part by (i) the integration of new virulence factors (e.g. speB, and the sal locus) and (ii) the construction of new regulation networks (e.g. rgg, and to some extent speB). PMID- 22666371 TI - A systematic prediction of multiple drug-target interactions from chemical, genomic, and pharmacological data. AB - In silico prediction of drug-target interactions from heterogeneous biological data can advance our system-level search for drug molecules and therapeutic targets, which efforts have not yet reached full fruition. In this work, we report a systematic approach that efficiently integrates the chemical, genomic, and pharmacological information for drug targeting and discovery on a large scale, based on two powerful methods of Random Forest (RF) and Support Vector Machine (SVM). The performance of the derived models was evaluated and verified with internally five-fold cross-validation and four external independent validations. The optimal models show impressive performance of prediction for drug-target interactions, with a concordance of 82.83%, a sensitivity of 81.33%, and a specificity of 93.62%, respectively. The consistence of the performances of the RF and SVM models demonstrates the reliability and robustness of the obtained models. In addition, the validated models were employed to systematically predict known/unknown drugs and targets involving the enzymes, ion channels, GPCRs, and nuclear receptors, which can be further mapped to functional ontologies such as target-disease associations and target-target interaction networks. This approach is expected to help fill the existing gap between chemical genomics and network pharmacology and thus accelerate the drug discovery processes. PMID- 22666372 TI - Label-free enrichment of functional cardiomyocytes using microfluidic deterministic lateral flow displacement. AB - Progress in cardiac cell replacement therapies and tissue engineering critically depends on our ability to isolate functional cardiomyocytes (CMs) from heterogeneous cell mixtures. Label-free enrichment of cardiomyocytes is desirable for future clinical application of cell based products. Taking advantage of the physical properties of CMs, a microfluidic system was designed to separate CMs from neonatal rat heart tissue digest based on size using the principles of deterministic lateral displacement (DLD). For the first time, we demonstrate enrichment of functional CMs up to 91 +/- 2.4% directly from the digested heart tissue without any pre-treatment or labeling. Enriched cardiomyocytes remained viable after sorting and formed contractile cardiac patches in 3-dimensional culture. The broad significance of this work lies in demonstrating functional cell enrichment from the primary tissue digest leading directly to the creation of the engineered tissue. PMID- 22666373 TI - Fishery-induced selection for slow somatic growth in European eel. AB - Both theoretical and experimental studies have shown that fishing mortality can induce adaptive responses in body growth rates of fishes in the opposite direction of natural selection. We compared body growth rates in European eel (Anguilla anguilla) from three Mediterranean stocks subject to different fishing pressure. Results are consistent with the hypotheses that i) fast-growing individuals are more likely to survive until sexual maturity than slow-growing ones under natural conditions (no fishing) and ii) fishing can select for slow growing individuals by removing fast-growing ones. Although the possibility of human-induced evolution seems remote for a panmictic species like such as the European eel, further research is desirable to assess the implications of the intensive exploitation on this critically endangered fish. PMID- 22666374 TI - A small fraction of strongly cooperative sodium channels boosts neuronal encoding of high frequencies. AB - Generation of action potentials (APs) is a crucial step in neuronal information processing. Existing biophysical models for AP generation almost universally assume that individual voltage-gated sodium channels operate statistically independently, and their avalanche-like opening that underlies AP generation is coordinated only through the transmembrane potential. However, biological ion channels of various types can exhibit strongly cooperative gating when clustered. Cooperative gating of sodium channels has been suggested to explain rapid onset dynamics and large threshold variability of APs in cortical neurons. It remains however unknown whether these characteristic properties of cortical APs can be reproduced if only a fraction of channels express cooperativity, and whether the presence of cooperative channels has an impact on encoding properties of neuronal populations. To address these questions we have constructed a conductance-based neuron model in which we continuously varied the size of a fraction [Formula: see text] of sodium channels expressing cooperativity and the strength of coupling between cooperative channels [Formula: see text]. We show that starting at a critical value of the coupling strength [Formula: see text], the activation curve of sodium channels develops a discontinuity at which opening of all coupled channels becomes an all-or-none event, leading to very rapid AP onsets. Models with a small fraction, [Formula: see text], of strongly cooperative channels generate APs with the most rapid onset dynamics. In this regime APs are triggered by simultaneous opening of the cooperative channel fraction and exhibit a pronounced biphasic waveform often observed in cortical neurons. We further show that presence of a small fraction of cooperative Na+ channels significantly improves the ability of neuronal populations to phase-lock their firing to high frequency input fluctuation. We conclude that presence of a small fraction of strongly coupled sodium channels can explain characteristic features of cortical APs and has a functional impact of enhancing the spike encoding of rapidly varying signals. PMID- 22666375 TI - The integrative taxonomic approach reveals host specific species in an encyrtid parasitoid species complex. AB - Integrated taxonomy uses evidence from a number of different character types to delimit species and other natural groupings. While this approach has been advocated recently, and should be of particular utility in the case of diminutive insect parasitoids, there are relatively few examples of its application in these taxa. Here, we use an integrated framework to delimit independent lineages in Encyrtus sasakii (Hymenoptera: Chalcidoidea: Encyrtidae), a parasitoid morphospecies previously considered a host generalist. Sequence variation at the DNA barcode (cytochrome c oxidase I, COI) and nuclear 28S rDNA loci were compared to morphometric recordings and mating compatibility tests, among samples of this species complex collected from its four scale insect hosts, covering a broad geographic range of northern and central China. Our results reveal that Encyrtus sasakii comprises three lineages that, while sharing a similar morphology, are highly divergent at the molecular level. At the barcode locus, the median K2P molecular distance between individuals from three primary populations was found to be 11.3%, well outside the divergence usually observed between Chalcidoidea conspecifics (0.5%). Corroborative evidence that the genetic lineages represent independent species was found from mating tests, where compatibility was observed only within populations, and morphometric analysis, which found that despite apparent morphological homogeneity, populations clustered according to forewing shape. The independent lineages defined by the integrated analysis correspond to the three scale insect hosts, suggesting the presence of host specific cryptic species. The finding of hidden host specificity in this species complex demonstrates the critical role that DNA barcoding will increasingly play in revealing hidden biodiversity in taxa that present difficulties for traditional taxonomic approaches. PMID- 22666376 TI - Overexpression of TRIM24 correlates with tumor progression in non-small cell lung cancer. AB - The objective of the current study was to investigate the expression pattern and clinicopathological significance of TRIM24 in patients with non-small cell lung cancer (NSCLC). The expression profile of TRIM24 in NSCLC tissues and adjacent noncancerous lung tissues was detected by immunohistochemistry. TRIM24 was found to be overexpressed in 81 of 113 (71.7%) human lung cancer samples and correlated with p-TNM stage (p = 0.0006), poor differentiation (p = 0.004), Ki67 index (p<0.0001), cyclin D1(p = 0.0096) and p-Rb expression (p = 0.0318). In addition, depleting TRIM24 expression by small interfering RNA inhibited growth and invasion in lung cell lines. Moreover, TRIM24 depletion induced cell cycle arrest at the G1/S boundary and induced apoptosis. Western blotting analysis revealed that knockdown of TRIM24 decreased the protein levels of Cyclin A, Cyclin B, Cyclin D1, cyclin E and p-Rb and increased P27 expression. These results indicate that TRIM24 plays an important role in NSCLC progression. PMID- 22666377 TI - Translation of EEG spatial filters from resting to motor imagery using independent component analysis. AB - Electroencephalogram (EEG)-based brain-computer interfaces (BCIs) often use spatial filters to improve signal-to-noise ratio of task-related EEG activities. To obtain robust spatial filters, large amounts of labeled data, which are often expensive and labor-intensive to obtain, need to be collected in a training procedure before online BCI control. Several studies have recently developed zero training methods using a session-to-session scenario in order to alleviate this problem. To our knowledge, a state-to-state translation, which applies spatial filters derived from one state to another, has never been reported. This study proposes a state-to-state, zero-training method to construct spatial filters for extracting EEG changes induced by motor imagery. Independent component analysis (ICA) was separately applied to the multi-channel EEG in the resting and the motor imagery states to obtain motor-related spatial filters. The resultant spatial filters were then applied to single-trial EEG to differentiate left- and right-hand imagery movements. On a motor imagery dataset collected from nine subjects, comparable classification accuracies were obtained by using ICA-based spatial filters derived from the two states (motor imagery: 87.0%, resting: 85.9%), which were both significantly higher than the accuracy achieved by using monopolar scalp EEG data (80.4%). The proposed method considerably increases the practicality of BCI systems in real-world environments because it is less sensitive to electrode misalignment across different sessions or days and does not require annotated pilot data to derive spatial filters. PMID- 22666378 TI - Visual scan paths and recognition of facial identity in autism spectrum disorder and typical development. AB - BACKGROUND: Previous research suggests that many individuals with autism spectrum disorder (ASD) have impaired facial identity recognition, and also exhibit abnormal visual scanning of faces. Here, two hypotheses accounting for an association between these observations were tested: i) better facial identity recognition is associated with increased gaze time on the Eye region; ii) better facial identity recognition is associated with increased eye-movements around the face. METHODOLOGY AND PRINCIPAL FINDINGS: Eye-movements of 11 children with ASD and 11 age-matched typically developing (TD) controls were recorded whilst they viewed a series of faces, and then completed a two alternative forced-choice recognition memory test for the faces. Scores on the memory task were standardized according to age. In both groups, there was no evidence of an association between the proportion of time spent looking at the Eye region of faces and age-standardized recognition performance, thus the first hypothesis was rejected. However, the 'Dynamic Scanning Index'--which was incremented each time the participant saccaded into and out of one of the core-feature interest areas- was strongly associated with age-standardized face recognition scores in both groups, even after controlling for various other potential predictors of performance. CONCLUSIONS AND SIGNIFICANCE: In support of the second hypothesis, results suggested that increased saccading between core-features was associated with more accurate face recognition ability, both in typical development and ASD. Causal directions of this relationship remain undetermined. PMID- 22666379 TI - Active versus passive training of a complex bimanual task: is prescriptive proprioceptive information sufficient for inducing motor learning? AB - Perceptual processes play an important role in motor learning. While it is evident that visual information greatly contributes to learning new movements, much less is known about provision of prescriptive proprioceptive information. Here, we investigated whether passive (proprioceptively-based) movement training was comparable to active training for learning a new bimanual task. Three groups practiced a bimanual coordination pattern with a 1:2 frequency ratio and a 90 degrees phase offset between both wrists with Lissajous feedback over the course of four days: 1) passive training; 2) active training; 3) no training (control). Retention findings revealed that passive as compared to active training resulted in equally successful acquisition of the frequency ratio but active training was more effective for acquisition of the new relative phasing between the limbs in the presence of augmented visual feedback. However, when this feedback was removed, performance of the new relative phase deteriorated in both groups whereas the frequency ratio was better preserved. The superiority of active over passive training in the presence of augmented feedback is hypothesized to result from active involvement in processes of error detection/correction and planning. PMID- 22666380 TI - Modelling psychological responses to the Great East Japan earthquake and nuclear incident. AB - The Great East Japan (Tohoku/Kanto) earthquake of March 2011 was followed by a major tsunami and nuclear incident. Several previous studies have suggested a number of psychological responses to such disasters. However, few previous studies have modelled individual differences in the risk perceptions of major events, or the implications of these perceptions for relevant behaviours. We conducted a survey specifically examining responses to the Great Japan earthquake and nuclear incident, with data collected 11-13 weeks following these events. 844 young respondents completed a questionnaire in three regions of Japan; Miyagi (close to the earthquake and leaking nuclear plants), Tokyo/Chiba (approximately 220 km from the nuclear plants), and Western Japan (Yamaguchi and Nagasaki, some 1000 km from the plants). Results indicated significant regional differences in risk perception, with greater concern over earthquake risks in Tokyo than in Miyagi or Western Japan. Structural equation analyses showed that shared normative concerns about earthquake and nuclear risks, conservation values, lack of trust in governmental advice about the nuclear hazard, and poor personal control over the nuclear incident were positively correlated with perceived earthquake and nuclear risks. These risk perceptions further predicted specific outcomes (e.g. modifying homes, avoiding going outside, contemplating leaving Japan). The strength and significance of these pathways varied by region. Mental health and practical implications of these findings are discussed in the light of the continuing uncertainties in Japan following the March 2011 events. PMID- 22666381 TI - Triptolide inhibits the proliferation of prostate cancer cells and down-regulates SUMO-specific protease 1 expression. AB - Recently, traditional Chinese medicine and medicinal herbs have attracted more attentions worldwide for its anti-tumor efficacy. Celastrol and Triptolide, two active components extracted from the Chinese herb Tripterygium wilfordii Hook F (known as Lei Gong Teng or Thunder of God Vine), have shown anti-tumor effects. Celastrol was identified as a natural 26 s proteasome inhibitor which promotes cell apoptosis and inhibits tumor growth. The effect and mechanism of Triptolide on prostate cancer (PCa) is not well studied. Here we demonstrated that Triptolide, more potent than Celastrol, inhibited cell growth and induced cell death in LNCaP and PC-3 cell lines. Triptolide also significantly inhibited the xenografted PC-3 tumor growth in nude mice. Moreover, Triptolide induced PCa cell apoptosis through caspases activation and PARP cleavage. Unbalance between SUMOylation and deSUMOylation was reported to play an important role in PCa progression. SUMO-specific protease 1 (SENP1) was thought to be a potential marker and therapeutical target of PCa. Importantly, we observed that Triptolide down-regulated SENP1 expression in both mRNA and protein levels in dose-dependent and time-dependent manners, resulting in an enhanced cellular SUMOylation in PCa cells. Meanwhile, Triptolide decreased AR and c-Jun expression at similar manners, and suppressed AR and c-Jun transcription activity. Furthermore, knockdown or ectopic SENP1, c-Jun and AR expression in PCa cells inhibited the Triptolide anti-PCa effects. Taken together, our data suggest that Triptolide is a natural compound with potential therapeutic value for PCa. Its anti-tumor activity may be attributed to mechanisms involving down-regulation of SENP1 that restores SUMOylation and deSUMOyaltion balance and negative regulation of AR and c-Jun expression that inhibits the AR and c-Jun mediated transcription in PCa. PMID- 22666382 TI - Genus paracoccidioides: Species recognition and biogeographic aspects. AB - BACKGROUND: Paracoccidioidomycosis is a systemic mycosis caused by Paracoccidioides brasiliensis (species S1, PS2, PS3), and Paracoccidioides lutzii. This work aimed to differentiate species within the genus Paracoccidioides, without applying multilocus sequencing, as well as to obtain knowledge of the possible speciation processes. METHODOLOGY/PRINCIPAL FINDINGS: Single nucleotide polymorphism analysis on GP43, ARF and PRP8 intein genes successfully distinguished isolates into four different species. Morphological evaluation indicated that elongated conidia were observed exclusively in P. lutzii isolates, while all other species (S1, PS2 and PS3) were indistinguishable. To evaluate the biogeographic events that led to the current geographic distribution of Paracoccidioides species and their sister species, Nested Clade and Likelihood Analysis of Geographic Range Evolution (LAGRANGE) analyses were applied. The radiation of Paracoccidioides started in northwest South America, around 11-32 million years ago, as calculated on the basis of ARF substitution rate, in the BEAST program. Vicariance was responsible for the divergence among S1, PS2 and P. lutzii and a recent dispersal generated the PS3 species, restricted to Colombia. Taking into account the ancestral areas revealed by the LAGRANGE analysis and the major geographic distribution of L. loboi in the Amazon basin, a region strongly affected by the Andes uplift and marine incursions in the Cenozoic era, we also speculate about the effect of these geological events on the vicariance between Paracoccidioides and L. loboi. CONCLUSIONS/SIGNIFICANCE: The use of at least 3 SNPs, but not morphological criteria, as markers allows us to distinguish among the four cryptic species of the genus Paracoccidioides. The work also presents a biogeographic study speculating on how these species might have diverged in South America, thus contributing to elucidating evolutionary aspects of the genus Paracoccidioides. PMID- 22666383 TI - Abnormal Wnt and PI3Kinase signaling in the malformed intestine of lama5 deficient mice. AB - Laminins are major constituents of basement membranes and are essential for tissue homeostasis. Laminin-511 is highly expressed in the intestine and its absence causes severe malformation of the intestine and embryonic lethality. To understand the mechanistic role of laminin-511 in tissue homeostasis, we used RNA profiling of embryonic intestinal tissue of lama5 knockout mice and identified a lama5 specific gene expression signature. By combining cell culture experiments with mediated knockdown approaches, we provide a mechanistic link between laminin alpha5 gene deficiency and the physiological phenotype. We show that laminin alpha5 plays a crucial role in both epithelial and mesenchymal cell behavior by inhibiting Wnt and activating PI3K signaling. We conclude that conflicting signals are elicited in the absence of lama5, which alter cell adhesion, migration as well as epithelial and muscle differentiation. Conversely, adhesion to laminin-511 may serve as a potent regulator of known interconnected PI3K/Akt and Wnt signaling pathways. Thus deregulated adhesion to laminin-511 may be instrumental in diseases such as human pathologies of the gut where laminin-511 is abnormally expressed as it is shown here. PMID- 22666385 TI - Does reviewing lead to better learning and decision making? Answers from a randomized stock market experiment. AB - BACKGROUND: The literature is not univocal about the effects of Peer Review (PR) within the context of constructivist learning. Due to the predominant focus on using PR as an assessment tool, rather than a constructivist learning activity, and because most studies implicitly assume that the benefits of PR are limited to the reviewee, little is known about the effects upon students who are required to review their peers. Much of the theoretical debate in the literature is focused on explaining how and why constructivist learning is beneficial. At the same time these discussions are marked by an underlying presupposition of a causal relationship between reviewing and deep learning. OBJECTIVES: The purpose of the study is to investigate whether the writing of PR feedback causes students to benefit in terms of: perceived utility about statistics, actual use of statistics, better understanding of statistical concepts and associated methods, changed attitudes towards market risks, and outcomes of decisions that were made. METHODS: We conducted a randomized experiment, assigning students randomly to receive PR or non-PR treatments and used two cohorts with a different time span. The paper discusses the experimental design and all the software components that we used to support the learning process: Reproducible Computing technology which allows students to reproduce or re-use statistical results from peers, Collaborative PR, and an AI-enhanced Stock Market Engine. RESULTS: The results establish that the writing of PR feedback messages causes students to experience benefits in terms of Behavior, Non-Rote Learning, and Attitudes, provided the sequence of PR activities are maintained for a period that is sufficiently long. PMID- 22666384 TI - Dynamic gene expression in the human cerebral cortex distinguishes children from adults. AB - In comparison with other primate species, humans have an extended juvenile period during which the brain is more plastic. In the current study we sought to examine gene expression in the cerebral cortex during development in the context of this adaptive plasticity. We introduce an approach designed to discriminate genes with variable as opposed to uniform patterns of gene expression and found that greater inter-individual variance is observed among children than among adults. For the 337 transcripts that show this pattern, we found a significant overrepresentation of genes annotated to the immune system process (pFDR ~/= 0). Moreover, genes known to be important in neuronal function, such as brain-derived neurotrophic factor (BDNF), are included among the genes more variably expressed in childhood. We propose that the developmental period of heightened childhood neuronal plasticity is characterized by more dynamic patterns of gene expression in the cerebral cortex compared to adulthood when the brain is less plastic. That an overabundance of these genes are annotated to the immune system suggests that the functions of these genes can be thought of not only in the context of antigen processing and presentation, but also in the context of nervous system development. PMID- 22666386 TI - Gaussian mixture model of heart rate variability. AB - Heart rate variability (HRV) is an important measure of sympathetic and parasympathetic functions of the autonomic nervous system and a key indicator of cardiovascular condition. This paper proposes a novel method to investigate HRV, namely by modelling it as a linear combination of Gaussians. Results show that three Gaussians are enough to describe the stationary statistics of heart variability and to provide a straightforward interpretation of the HRV power spectrum. Comparisons have been made also with synthetic data generated from different physiologically based models showing the plausibility of the Gaussian mixture parameters. PMID- 22666387 TI - Targeting a newly established spontaneous feline fibrosarcoma cell line by gene transfer. AB - Fibrosarcoma is a deadly disease in cats and is significantly more often located at classical vaccine injections sites. More rare forms of spontaneous non vaccination site (NSV) fibrosarcomas have been described and have been found associated to genetic alterations. Purpose of this study was to compare the efficacy of adenoviral gene transfer in NVS fibrosarcoma. We isolated and characterized a NVS fibrosarcoma cell line (Cocca-6A) from a spontaneous fibrosarcoma that occurred in a domestic calico cat. The feline cells were karyotyped and their chromosome number was counted using a Giemsa staining. Adenoviral gene transfer was verified by western blot analysis. Flow cytometry assay and Annexin-V were used to study cell-cycle changes and cell death of transduced cells. Cocca-6A fibrosarcoma cells were morphologically and cytogenetically characterized. Giemsa block staining of metaphase spreads of the Cocca-6A cells showed deletion of one of the E1 chromosomes, where feline p53 maps. Semi-quantitative PCR demonstrated reduction of p53 genomic DNA in the Cocca-6A cells. Adenoviral gene transfer determined a remarkable effect on the viability and growth of the Cocca-6A cells following single transduction with adenoviruses carrying Mda-7/IL-24 or IFN-gamma or various combination of RB/p105, Ras-DN, IFN-gamma, and Mda-7 gene transfer. Therapy for feline fibrosarcomas is often insufficient for long lasting tumor eradication. More gene transfer studies should be conducted in order to understand if these viral vectors could be applicable regardless the origin (spontaneous vs. vaccine induced) of feline fibrosarcomas. PMID- 22666388 TI - Human movement is both diffusive and directed. AB - Understanding the influence of the built environment on human movement requires quantifying spatial structure in a general sense. Because of the difficulty of this task, studies of movement dynamics often ignore spatial heterogeneity and treat movement through journey lengths or distances alone. This study analyses public bicycle data from central London to reveal that, although journey distances, directions, and frequencies of occurrence are spatially variable, their relative spatial patterns remain largely constant, suggesting the influence of a fixed spatial template. A method is presented to describe this underlying space in terms of the relative orientation of movements toward, away from, and around locations of geographical or cultural significance. This produces two fields: one of convergence and one of divergence, which are able to accurately reconstruct the observed spatial variations in movement. These two fields also reveal categorical distinctions between shorter journeys merely serving diffusion away from significant locations, and longer journeys intentionally serving transport between spatially distinct centres of collective importance. Collective patterns of human movement are thus revealed to arise from a combination of both diffusive and directed movement, with aggregate statistics such as mean travel distances primarily determined by relative numbers of these two kinds of journeys. PMID- 22666389 TI - Cell line specific modulation of extracellular abeta42 by Hsp40. AB - Heat shock proteins (Hsps) are a set of molecular chaperones involved in cellular repair. They provide protective mechanisms that allow cells to survive potentially lethal insults, In response to a conditioning stress their expression is increased. Here we examined the connection between Hsps and Abeta(42), the amyloid peptide involved in the pathological sequence of Alzheimer's disease (AD). Extracellular Abeta(42) associates with neuronal cells and is a major constituent of senile plaques, one of the hallmarks of AD. Although Hsps are generally thought to prevent accumulation of misfolded proteins, there is a lack of mechanistic evidence that heat shock chaperones directly modulate Abeta(42) toxicity. In this study we show that neither extracellular Abeta(42) nor Abeta(42/)PrP(C) trigger the heat shock response in neurons. To address the influence of the neuroprotective heat shock response on cellular Abeta(42), Western analysis of Abeta(42) was performed following external Abeta(42) application. Five hours after a conditioning heat shock, Abeta(42) association with CAD cells was increased compared to control neurons. However, at forty-eight hours following heat shock Abeta(42) levels were reduced compared to that found for control cells. Moreover, transient transfection of the stress induced Hsp40, decreased CAD levels of Abeta(42). In contrast to CAD cells, hippocampal neurons transfected with Hsp40 retained Abeta(42) indicating that Hsp40 modulation of Abeta(42) proteostasis is cell specific. Mutation of the conserved HPD motif within Hsp40 significantly reduced the Hsp40-mediated Abeta(42) increase in hippocampal cultures indicating the importance of this motif in regulating cellular Abeta(42). Our data reveal a biochemical link between Hsp40 expression and Abeta(42) proteostasis that is cell specific. Therefore, increasing Hsp40 therapeutically with the intention of interfering with the pathogenic cascade leading to neurodegeneration in AD should be pursued with caution. PMID- 22666390 TI - Novel mechanism of action on Hedgehog signaling by a suppressor of fused carboxy terminal variant. AB - The Suppressor of Fused (SUFU) protein plays an essential role in the Hedgehog (HH) signaling pathway, by regulation of the GLI transcription factors. Two major isoforms of human SUFU are known, a full-length (SUFU-FL) and a carboxy-terminal truncated (SUFU- DeltaC) variant. Even though SUFU- DeltaC is expressed at an equivalent level as SUFU-FL in certain tissues, the function of SUFU-DeltaC and its impact on HH signal transduction is still unclear. In two cell lines from rhabdomyosarcoma, a tumor type associated with deregulated HH signaling, SUFU DeltaC mRNA was expressed at comparable levels as SUFU-FL mRNA, but at the protein level only low amounts of SUFU-DeltaC were detectable. Heterologous expression provided support to the notion that the SUFU-DeltaC protein is less stable compared to SUFU-FL. Despite this, biochemical analysis revealed that SUFU DeltaC could repress GLI2 and GLI1DeltaN, but not GLI1FL, transcriptional activity to the same extent as SUFU-FL. Moreover, under conditions of activated HH signaling SUFU-DeltaC was more effective than SUFU-FL in inhibiting GLI1DeltaN. Importantly, co-expression with GLI1FL indicated that SUFU-DeltaC but not SUFU-FL reduced the protein levels of GLI1FL. Additionally, confocal microscopy revealed a co-localization of GLI1FL with SUFU-DeltaC but not SUFU-FL in aggregate structures. Moreover, specific siRNA mediated knock-down of SUFU DeltaC resulted in up-regulation of the protein levels of GLI1FL and the HH signaling target genes PTCH1 and HHIP. Our results are therefore suggesting the presence of novel regulatory controls in the HH signaling pathway, which are elicited by the distinct mechanism of action of the two alternative spliced SUFU proteins. PMID- 22666391 TI - Expression of Toll-like receptors in the developing brain. AB - Toll-like receptors (TLR) are key players of the innate and adaptive immune response in vertebrates. The original protein Toll in Drosophila melanogaster regulates both host defense and morphogenesis during development. Making use of real-time PCR, in situ hybridization, and immunohistochemistry we systematically examined the expression of TLR1-9 and the intracellular adaptor molecules MyD88 and TRIF during development of the mouse brain. Expression of TLR7 and TLR9 in the brain was strongly regulated during different embryonic, postnatal, and adult stages. In contrast, expression of TLR1-6, TLR8, MyD88, and TRIF mRNA displayed no significant changes in the different phases of brain development. Neurons of various brain regions including the neocortex and the hippocampus were identified as the main cell type expressing both TLR7 and TLR9 in the developing brain. Taken together, our data reveal specific expression patterns of distinct TLRs in the developing mouse brain and lay the foundation for further investigation of the pathophysiological significance of these receptors for developmental processes in the central nervous system of vertebrates. PMID- 22666392 TI - Immune and viral correlates of "secondary viral control" after treatment interruption in chronically HIV-1 infected patients. AB - Upon interruption of antiretroviral therapy, HIV-infected patients usually show viral load rebound to pre-treatment levels. Four patients, hereafter referred to as secondary controllers (SC), were identified who initiated therapy during chronic infection and, after stopping treatment, could control virus replication at undetectable levels for more than six months. In the present study we set out to unravel possible viral and immune parameters or mechanisms of this phenomenon by comparing secondary controllers with elite controllers and non-controllers, including patients under HAART. As candidate correlates of protection, virus growth kinetics, levels of intracellular viral markers, several aspects of HIV specific CD4+ and CD8+ T cell function and HIV neutralizing antibodies were investigated. As expected all intracellular viral markers were lower in aviremic as compared to viremic subjects, but in addition both elite and secondary controllers had lower levels of viral unspliced RNA in PBMC as compared to patients on HAART. Ex vivo cultivation of the virus from CD4+ T cells of SC consistently failed in one patient and showed delayed kinetics in the three others. Formal in vitro replication studies of these three viruses showed low to absent growth in two cases and a virus with normal fitness in the third case. T cell responses toward HIV peptides, evaluated in IFN-gamma ELISPOT, revealed no significant differences in breadth, magnitude or avidity between SC and all other patient groups. Neither was there a difference in polyfunctionality of CD4+ or CD8+ T cells, as evaluated with intracellular cytokine staining. However, secondary and elite controllers showed higher proliferative responses to Gag and Pol peptides. SC also showed the highest level of autologous neutralizing antibodies. These data suggest that higher T cell proliferative responses and lower replication kinetics might be instrumental in secondary viral control in the absence of treatment. PMID- 22666393 TI - Bacterial communities in the sediments of Dianchi Lake, a partitioned eutrophic waterbody in China. AB - Bacteria play an important role in the decomposition and cycling of a variety of compounds in freshwater aquatic environments, particularly nutrient-rich eutrophic lakes. A unique Chinese eutrophic lake--Dianchi--was selected for study because it has two separate and distinct basins, Caohai with higher organic carbon levels and Waihai with lower organic carbon levels. Sediment bacterial communities were studied in the two basins using samples collected in each season from June 2010 to March 2011. Barcoded pyrosequencing based on the 16 S rRNA gene found that certain common phyla, Proteobacteria, Bacteroidetes, Firmicutes and Chloroflexi, were dominant in the sediments from both basins. However, from the class to genus level, the dominant bacterial groups found in the sediments were distinct between the two basins. Correlation analysis revealed that, among the environmental parameters examined, total organic carbon (TOC) accounted for the greatest proportion of variability in bacterial community. Interestingly, study results suggest that increasing allochthonous organic carbon could enhance bacterial diversity and biomass in the sediment. In addition, analysis of function genes (amoA and nosZ) demonstrated that ammonia-oxidizing bacteria (AOB) were dominant in sediments, with 99% belonging to Nitrosomonas. Denitrifying bacteria were comparatively diverse and were associated with some cultivatable bacteria. PMID- 22666394 TI - ILK induces cardiomyogenesis in the human heart. AB - BACKGROUND: Integrin-linked kinase (ILK) is a widely conserved serine/threonine kinase that regulates diverse signal transduction pathways implicated in cardiac hypertrophy and contractility. In this study we explored whether experimental overexpression of ILK would up-regulate morphogenesis in the human fetal heart. METHODOLOGY/PRINCIPAL FINDINGS: Primary cultures of human fetal myocardial cells (19-22 weeks gestation) yielded scattered aggregates of cardioblasts positive for the early cardiac lineage marker nk * 2.5 and containing nascent sarcomeres. Cardiac cells in colonies uniformly expressed the gap junction protein connexin 43 (C * 43) and displayed a spectrum of differentiation with only a subset of cells exhibiting the late cardiomyogenic marker troponin T (cTnT) and evidence of electrical excitability. Adenovirus-mediated overexpression of ILK potently increased the number of new aggregates of primitive cardioblasts (p<0.001). The number of cardioblast colonies was significantly decreased (p<0.05) when ILK expression was knocked down with ILK targeted siRNA. Interestingly, overexpression of the activation resistant ILK mutant (ILK(R211A)) resulted in much greater increase in the number of new cell aggregates as compared to overexpression of wild-type ILK (ILK(WT)). The cardiomyogenic effects of ILK(R211A) and ILK(WT) were accompanied by concurrent activation of beta-catenin (p<0.001) and increase expression of progenitor cell marker islet-1, which was also observed in lysates of transgenic mice with cardiac-specific over-expression of ILK(R211A) and ILK(WT). Finally, endogenous ILK expression was shown to increase in concert with those of cardiomyogenic markers during directed cardiomyogenic differentiation in human embryonic stem cells (hESCs). CONCLUSIONS/SIGNIFICANCE: In the human fetal heart ILK activation is instructive to the specification of mesodermal precursor cells towards a cardiomyogenic lineage. Induction of cardiomyogenesis by ILK overexpression bypasses the requirement of proximal PI3K activation for transduction of growth factor- and beta1-integrin-mediated differentiation signals. Altogether, our data indicate that ILK represents a novel regulatory checkpoint during human cardiomyogenesis. PMID- 22666395 TI - Functional implications of species differences in the size and morphology of the isthmo optic nucleus (ION) in birds. AB - In birds, there is a retinofugal projection from the brain to the retina originating from the isthmo optic nucleus (ION) in the midbrain. Despite a large number of anatomical, physiological and histochemical studies, the function of this retinofugal system remains unclear. Several functions have been proposed including: gaze stabilization, pecking behavior, dark adaptation, shifting attention, and detection of aerial predators. This nucleus varies in size and organization among some species, but the relative size and morphology of the ION has not been systematically studied. Here, we present a comparison of the relative size and morphology of the ION in 81 species of birds, representing 17 different orders. Our results show that several orders of birds, besides those previously reported, have a large, well-organized ION, including: hummingbirds, woodpeckers, coots and allies, and kingfishers. At the other end of the spectrum, parrots, herons, waterfowl, owls and diurnal raptors have relatively small ION volumes. ION also appears to be absent or unrecognizable is several taxa, including one of the basal avian groups, the tinamous, which suggests that the ION may have evolved only in the more modern group of birds, Neognathae. Finally, we demonstrate that evolutionary changes in the relative size and the cytoarchitectonic organization of ION have occurred largely independent of phylogeny. The large relative size of the ION in orders with very different lifestyles and feeding behaviors suggest there is no clear association with pecking behavior or predator detection. Instead, our results suggest that the ION is more complex and enlarged in birds that have eyes that are emmetropic in some parts of the visual field and myopic in others. We therefore posit that the ION is involved in switching attention between two parts of the retina i.e. from an emmetropic to a myopic part of the retina. PMID- 22666396 TI - Analysis of dehydration and strength in elite badminton players. AB - BACKGROUND: The negative effects of dehydration on aerobic activities are well established. However, it is unknown how dehydration affects intermittent sports performance. The purpose of this study was to identify the level of dehydration in elite badminton players and its relation to muscle strength and power production. METHODOLOGY: Seventy matches from the National Spanish badminton championship were analyzed (46 men's singles and 24 women's singles). Before and after each match, jump height and power production were determined during a countermovement jump on a force platform. Participants' body weight and a urine sample were also obtained before and after each match. The amount of liquid that the players drank during the match was also calculated by weighing their individual drinking bottles. RESULTS AND DISCUSSION: Sweat rate during the game was 1.14 +/- 0.46 l/h in men and 1.02 +/- 0.64 l/h in women. The players rehydrated at a rate of 1.10 +/- 0.55 l/h and 1.01 +/- 0.44 l/h in the male and female groups respectively. Thus, the dehydration attained during the game was only 0.37 +/- 0.50% in men and 0.32 +/- 0.83% in women. No differences were found in any of the parameters analyzed during the vertical jump (men: from 31.82 +/- 5.29 to 32.90 +/- 4.49 W/kg; p>0.05, women: from 26.36 +/- 4.73 to 27.25 +/- 4.44 W/kg; p>0.05). Post-exercise urine samples revealed proteinuria (60.9% of cases in men and 66.7% in women), leukocyturia (men = 43.5% and women = 50.0%) and erythrocyturia (men = 50.0% and women = 21.7%). CONCLUSIONS: Despite a moderate sweat rate, badminton players adequately hydrated during a game and thus the dehydration attained was low. The badminton match did not cause muscle fatigue but it significantly increased the prevalence of proteinuria, leukocyturia and erythrocyturia. PMID- 22666398 TI - Spontaneous prediction error generation in schizophrenia. AB - Goal-directed human behavior is enabled by hierarchically-organized neural systems that process executive commands associated with higher brain areas in response to sensory and motor signals from lower brain areas. Psychiatric diseases and psychotic conditions are postulated to involve disturbances in these hierarchical network interactions, but the mechanism for how aberrant disease signals are generated in networks, and a systems-level framework linking disease signals to specific psychiatric symptoms remains undetermined. In this study, we show that neural networks containing schizophrenia-like deficits can spontaneously generate uncompensated error signals with properties that explain psychiatric disease symptoms, including fictive perception, altered sense of self, and unpredictable behavior. To distinguish dysfunction at the behavioral versus network level, we monitored the interactive behavior of a humanoid robot driven by the network. Mild perturbations in network connectivity resulted in the spontaneous appearance of uncompensated prediction errors and altered interactions within the network without external changes in behavior, correlating to the fictive sensations and agency experienced by episodic disease patients. In contrast, more severe deficits resulted in unstable network dynamics resulting in overt changes in behavior similar to those observed in chronic disease patients. These findings demonstrate that prediction error disequilibrium may represent an intrinsic property of schizophrenic brain networks reporting the severity and variability of disease symptoms. Moreover, these results support a systems-level model for psychiatric disease that features the spontaneous generation of maladaptive signals in hierarchical neural networks. PMID- 22666397 TI - Resting-state multi-spectrum functional connectivity networks for identification of MCI patients. AB - In this paper, a high-dimensional pattern classification framework, based on functional associations between brain regions during resting-state, is proposed to accurately identify MCI individuals from subjects who experience normal aging. The proposed technique employs multi-spectrum networks to characterize the complex yet subtle blood oxygenation level dependent (BOLD) signal changes caused by pathological attacks. The utilization of multi-spectrum networks in identifying MCI individuals is motivated by the inherent frequency-specific properties of BOLD spectrum. It is believed that frequency specific information extracted from different spectra may delineate the complex yet subtle variations of BOLD signals more effectively. In the proposed technique, regional mean time series of each region-of-interest (ROI) is band-pass filtered (0.025 <= f <= 0.100 Hz) before it is decomposed into five frequency sub-bands. Five connectivity networks are constructed, one from each frequency sub-band. Clustering coefficient of each ROI in relation to the other ROIs are extracted as features for classification. Classification accuracy was evaluated via leave-one out cross-validation to ensure generalization of performance. The classification accuracy obtained by this approach is 86.5%, which is an increase of at least 18.9% from the conventional full-spectrum methods. A cross-validation estimation of the generalization performance shows an area of 0.863 under the receiver operating characteristic (ROC) curve, indicating good diagnostic power. It was also found that, based on the selected features, portions of the prefrontal cortex, orbitofrontal cortex, temporal lobe, and parietal lobe regions provided the most discriminant information for classification, in line with results reported in previous studies. Analysis on individual frequency sub-bands demonstrated that different sub-bands contribute differently to classification, providing extra evidence regarding frequency-specific distribution of BOLD signals. Our MCI classification framework, which allows accurate early detection of functional brain abnormalities, makes an important positive contribution to the treatment management of potential AD patients. PMID- 22666399 TI - Tumor necrosis factor-alpha induced protein 8 polymorphism and risk of non Hodgkin's lymphoma in a Chinese population: a case-control study. AB - BACKGROUND: Non-Hodgkin's lymphoma (NHL) has been reported to be associated with autoimmune and pro-inflammatory response, and genetic polymorphisms of candidate genes involved in autoimmune and pro-inflammatory response may influence the susceptibility to NHL. To evaluate the role of such genetic variations in risk of NHL, we conducted a case-control study of 514 NHL patients and 557 cancer-free controls in a Chinese population. METHOD: We used the Taqman assay to genotype six potentially functional single nucleotide polymorphisms (SNPs) in six previously reported inflammation and immune-related genes (TNF rs1799964T>C, LTA rs1800683G>A, IL-10 rs1800872T>G, LEP rs2167270G>A, LEPR rs1327118C>G, TNFAIP8 rs1045241C>T). Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (95% CI). RESULTS: We observed a significantly increased risk of NHL associated with the TNFAIP8 rs1045241C>T polymorphism (adjusted OR = 3.03; 95% CI = 1.68-5.45 for TT vs. CC and adjusted OR = 2.03; 95% CI = 1.53-2.69 for CT/TT vs. CC). The risk associated with the T allele was more evident in subgroups of 40-60 year-old, non-smokers or light-smokers (less than 25 pack-years), and subjects with normal weight or overweight. Risk for both B and T cell non-Hodgkin's lymphoma was elevated for CT/TT genotypes (adjusted OR = 1.95, 95% CI = 1.41-2.70 for B cell NHL and adjusted OR = 2.22, 95% CI = 1.49 3.30 for T cell NHL), particularly for DLBCL (adjusted OR = 2.01, 95%CI = 1.41 2.85) and FL (adjusted OR = 2.53, 95% CI = 1.17-5.45). These risks were not observed for variant genotypes of other five SNPs compared with their common homozygous genotypes. CONCLUSIONS: The polymorphism of TNFAIP8 rs1045241C>T may contribute to NHL susceptibility in a Chinese population. Further large-scale and well-designed studies are needed to confirm these results. PMID- 22666400 TI - Office space bacterial abundance and diversity in three metropolitan areas. AB - People in developed countries spend approximately 90% of their lives indoors, yet we know little about the source and diversity of microbes in built environments. In this study, we combined culture-based cell counting and multiplexed pyrosequencing of environmental ribosomal RNA (rRNA) gene sequences to investigate office space bacterial diversity in three metropolitan areas. Five surfaces common to all offices were sampled using sterile double-tipped swabs, one tip for culturing and one for DNA extraction, in 30 different offices per city (90 offices, 450 total samples). 16S rRNA gene sequences were PCR amplified using bar-coded "universal" bacterial primers from 54 of the surfaces (18 per city) and pooled for pyrosequencing. A three-factorial Analysis of Variance (ANOVA) found significant differences in viable bacterial abundance between offices inhabited by men or women, among the various surface types, and among cities. Multiplex pyrosequencing identified more than 500 bacterial genera from 20 different bacterial divisions. The most abundant of these genera tended to be common inhabitants of human skin, nasal, oral or intestinal cavities. Other commonly occurring genera appeared to have environmental origins (e.g., soils). There were no significant differences in the bacterial diversity between offices inhabited by men or women or among surfaces, but the bacterial community diversity of the Tucson samples was clearly distinguishable from that of New York and San Francisco, which were indistinguishable. Overall, our comprehensive molecular analysis of office building microbial diversity shows the potential of these methods for studying patterns and origins of indoor bacterial contamination. "[H]umans move through a sea of microbial life that is seldom perceived except in the context of potential disease and decay." - Feazel et al. (2009). PMID- 22666401 TI - Surgery for valvular heart disease: a population-based study in a Brazilian urban center. AB - BACKGROUND: In middle income countries, the burden of rheumatic heart disease (RHD) remains high, but the prevalence of other heart valve diseases may rise as the population life expectancy increases. Here, we compared population-based data on surgical procedures to assess the relative importance of causes of heart valve disease in Salvador, Brazil. METHODOLOGY/PRINCIPAL FINDINGS: Medical charts of patients who underwent surgery for valvular heart disease from January 2002 December 2005 were reviewed. Incidence of surgery for valvular heart disease was calculated. Logistic regression was used to identify factors associated with in hospital death following surgery. The most common etiologies for valvular dysfunction in 491 valvular heart surgery patients were RHD (60.3%), degenerative valve disease (15.3%), and endocarditis (4.5%). Mean annual incidence for surgeries due to any valvular heart diseases, RHD, and degenerative valvular disease were 5.02, 3.03, and 0.77 per 100,000 population, respectively. Incidence of surgery due to RHD was highest in young adults; procedures were predominantly paid by the public health sector. In contrast, the incidence of surgery due to degenerative valvular disease was highest among those older than 60 years of age; procedures were mostly paid by the private sector. The overall in-hospital case fatality ratio was 11.9%. Independent factors associated with death included increase in age (odds ratio: 1.04 per year of age; 95% confidence interval: 1.02 1.06), endocarditis (6.35; 1.92-21.04), multiple valve operative procedures (4.35; 2.12-8.95), and prior heart valve surgery (2.49; 1.05-5.87). CONCLUSIONS/SIGNIFICANCE: RHD remains the main cause for valvular heart surgery in Salvador, which primarily affects young adults without private health insurance. In contrast, surgery due to degenerative valvular disease primarily impacts the elderly with private health insurance. Strategies to reduce the burden of valvular heart disease will need to address the disparate factors that contribute to RHD as well as degenerative valve disease. PMID- 22666402 TI - Ultra-deep pyrosequencing detects conserved genomic sites and quantifies linkage of drug-resistant amino acid changes in the hepatitis B virus genome. AB - BACKGROUND: Selection of amino acid substitutions associated with resistance to nucleos(t)ide-analog (NA) therapy in the hepatitis B virus (HBV) reverse transcriptase (RT) and their combination in a single viral genome complicates treatment of chronic HBV infection and may affect the overlapping surface coding region. In this study, the variability of an overlapping polymerase-surface region, critical for NA resistance, is investigated before treatment and under antiviral therapy, with assessment of NA-resistant amino acid changes simultaneously occurring in the same genome (linkage analysis) and their influence on the surface coding region. METHODOLOGY/PRINCIPAL FINDINGS: Serum samples obtained from chronic HBV-infected patients at pre-treatment and during sequential NA treatment with lamivudine, adefovir, and entecavir were analyzed by ultra-deep pyrosequencing (UDPS) using the GS-FLX platform (454 Life Sciences Roche). The pre-treatment HBV quasispecies was not enriched with NA-resistant substitutions. The frequencies of this type of substitutions at pre-treatment did not predict the frequencies observed during lamivudine treatment. On linkage analysis of the RT region studied, NA-resistant HBV variants (except for rtA181T) were present in combinations of amino acid substitutions that increased in complexity after viral breakthrough to entecavir, at which time the combined variant rtL180M-S202G-M204V-V207I predominated. In the overlapping surface region, NA-resistant substitutions caused selection of stop codons in a significant percentage of sequences both at pre-treatment and during sequential treatment; the rtA181T substitution, related to sW172stop, predominated during treatment with lamivudine and adefovir. A highly conserved RT residue (rtL155), even more conserved than the essential residues in the RT catalytic motif YMDD, was identified in all samples. CONCLUSIONS: UDPS methodology enabled quantification of HBV quasispecies variants, even those harboring complex combinations of amino acid changes. The high percentage of potentially defective genomes, especially in the surface region, suggests effective trans complementation of these variants. PMID- 22666403 TI - Glial processes at the Drosophila larval neuromuscular junction match synaptic growth. AB - Glia are integral participants in synaptic physiology, remodeling and maturation from blowflies to humans, yet how glial structure is coordinated with synaptic growth is unknown. To investigate the dynamics of glial development at the Drosophila larval neuromuscular junction (NMJ), we developed a live imaging system to establish the relationship between glia, neuronal boutons, and the muscle subsynaptic reticulum. Using this system we observed processes from two classes of peripheral glia present at the NMJ. Processes from the subperineurial glia formed a blood-nerve barrier around the axon proximal to the first bouton. Processes from the perineurial glial extended beyond the end of the blood-nerve barrier into the NMJ where they contacted synapses and extended across non synaptic muscle. Growth of the glial processes was coordinated with NMJ growth and synaptic activity. Increasing synaptic size through elevated temperature or the highwire mutation increased the extent of glial processes at the NMJ and conversely blocking synaptic activity and size decreased the presence and size of glial processes. We found that elevated temperature was required during embryogenesis in order to increase glial expansion at the nmj. Therefore, in our live imaging system, glial processes at the NMJ are likely indirectly regulated by synaptic changes to ensure the coordinated growth of all components of the tripartite larval NMJ. PMID- 22666404 TI - ZyFISH: a simple, rapid and reliable zygosity assay for transgenic mice. AB - Microinjection of DNA constructs into fertilized mouse oocytes typically results in random transgene integration at a single genomic locus. The resulting transgenic founders can be used to establish hemizygous transgenic mouse lines. However, practical and experimental reasons often require that such lines be bred to homozygosity. Transgene zygosity can be determined by progeny testing assays which are expensive and time-consuming, by quantitative Southern blotting which is labor-intensive, or by quantitative PCR (qPCR) which requires transgene specific design. Here, we describe a zygosity assessment procedure based on fluorescent in situ hybridization (zyFISH). The zyFISH protocol entails the detection of transgenic loci by FISH and the concomitant assignment of homozygosity using a concise and unbiased scoring system. The method requires small volumes of blood, is scalable to at least 40 determinations per assay, and produces results entirely consistent with the progeny testing assay. This combination of reliability, simplicity and cost-effectiveness makes zyFISH a method of choice for transgenic mouse zygosity determinations. PMID- 22666405 TI - Adverse metabolic response to regular exercise: is it a rare or common occurrence? AB - BACKGROUND: Individuals differ in the response to regular exercise. Whether there are people who experience adverse changes in cardiovascular and diabetes risk factors has never been addressed. METHODOLOGY/PRINCIPAL FINDINGS: An adverse response is defined as an exercise-induced change that worsens a risk factor beyond measurement error and expected day-to-day variation. Sixty subjects were measured three times over a period of three weeks, and variation in resting systolic blood pressure (SBP) and in fasting plasma HDL-cholesterol (HDL-C), triglycerides (TG), and insulin (FI) was quantified. The technical error (TE) defined as the within-subject standard deviation derived from these measurements was computed. An adverse response for a given risk factor was defined as a change that was at least two TEs away from no change but in an adverse direction. Thus an adverse response was recorded if an increase reached 10 mm Hg or more for SBP, 0.42 mmol/L or more for TG, or 24 pmol/L or more for FI or if a decrease reached 0.12 mmol/L or more for HDL-C. Completers from six exercise studies were used in the present analysis: Whites (N = 473) and Blacks (N = 250) from the HERITAGE Family Study; Whites and Blacks from DREW (N = 326), from INFLAME (N = 70), and from STRRIDE (N = 303); and Whites from a University of Maryland cohort (N = 160) and from a University of Jyvaskyla study (N = 105), for a total of 1,687 men and women. Using the above definitions, 126 subjects (8.4%) had an adverse change in FI. Numbers of adverse responders reached 12.2% for SBP, 10.4% for TG, and 13.3% for HDL-C. About 7% of participants experienced adverse responses in two or more risk factors. CONCLUSIONS/SIGNIFICANCE: Adverse responses to regular exercise in cardiovascular and diabetes risk factors occur. Identifying the predictors of such unwarranted responses and how to prevent them will provide the foundation for personalized exercise prescription. PMID- 22666406 TI - Dioxin induces genomic instability in mouse embryonic fibroblasts. AB - Ionizing radiation and certain other exposures have been shown to induce genomic instability (GI), i.e., delayed genetic damage observed many cell generations later in the progeny of the exposed cells. The aim of this study was to investigate induction of GI by a nongenotoxic carcinogen, 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD). Mouse embryonic fibroblasts (C3H10T1/2) were exposed to 1, 10 or 100 nM TCDD for 2 days. Micronuclei (MN) and expression of selected cancer-related genes were assayed both immediately and at a delayed point in time (8 days). For comparison, similar experiments were done with cadmium, a known genotoxic agent. TCDD treatment induced an elevated frequency of MN at 8 days, but not directly after the exposure. TCDD-induced alterations in gene expression were also mostly delayed, with more changes observed at 8 days than at 2 days. Exposure to cadmium produced an opposite pattern of responses, with pronounced effects immediately after exposure but no increase in MN and few gene expression changes at 8 days. Although all responses to TCDD alone were delayed, menadione-induced DNA damage (measured by the Comet assay), was found to be increased directly after a 2-day TCDD exposure, indicating that the stability of the genome was compromised already at this time point. The results suggested a flat dose-response relationship consistent with dose-response data reported for radiation-induced GI. These findings indicate that TCDD, although not directly genotoxic, induces GI, which is associated with impaired DNA damage response. PMID- 22666407 TI - Synthesis and biological evaluation of phenanthrenes as cytotoxic agents with pharmacophore modeling and ChemGPS-NP prediction as topo II inhibitors. AB - In a structure-activity relationship (SAR) study, 3-methoxy-1,4 phenanthrenequinones, calanquinone A (6a), denbinobin (6b), 5-OAc-calanquinone A (7a) and 5-OAc-denbinobin (7b), have significantly promising cytotoxicity against various human cancer cell lines (IC(50) 0.08-1.66 ug/mL). Moreover, we also established a superior pharmacophore model for cytotoxicity (r = 0.931) containing three hydrogen bond acceptors (HBA1, HBA2 and HBA3) and one hydrophobic feature (HYD) against MCF-7 breast cancer cell line. The pharmacophore model indicates that HBA3 is an essential feature for the oxygen atom of 5-OH in 6a-b and for the carbonyl group of 5-OCOCH(3) in 7a-b, important for their cytotoxic properties. The SAR for moderately active 5a-b (5-OCH(3)), and highly active 6a-b and 7a-b, are also elaborated in a spatial aspect model. Further rational design and synthesis of new cytotoxic phenanthrene analogs can be implemented via this model. Additionally, employing a ChemGPS-NP based model for cytotoxicity mode of action (MOA) provides support for a preliminary classification of compounds 6a-b as topoisomerase II inhibitors. PMID- 22666408 TI - Adaptation to visual feedback delay influences visuomotor learning. AB - Computational theory of motor control suggests that the brain continuously monitors motor commands, to predict their sensory consequences before actual sensory feedback becomes available. Such prediction error is a driving force of motor learning, and therefore appropriate associations between motor commands and delayed sensory feedback signals are crucial. Indeed, artificially introduced delays in visual feedback have been reported to degrade motor learning. However, considering our perceptual ability to causally bind our own actions with sensory feedback, demonstrated by the decrease in the perceived time delay following repeated exposure to an artificial delay, we hypothesized that such perceptual binding might alleviate deficits of motor learning associated with delayed visual feedback. Here, we evaluated this hypothesis by investigating the ability of human participants to adapt their reaching movements in response to a novel visuomotor environment with 3 visual feedback conditions--no-delay, sudden-delay, and adapted-delay. To introduce novelty into the trials, the cursor position, which originally indicated the hand position in baseline trials, was rotated around the starting position. In contrast to the no-delay condition, a 200-ms delay was artificially introduced between the cursor and hand positions during the presence of visual rotation (sudden-delay condition), or before the application of visual rotation (adapted-delay condition). We compared the learning rate (representing how the movement error modifies the movement direction in the subsequent trial) between the 3 conditions. In comparison with the no-delay condition, the learning rate was significantly degraded for the sudden-delay condition. However, this degradation was significantly alleviated by prior exposure to the delay (adapted-delay condition). Our data indicate the importance of appropriate temporal associations between motor commands and sensory feedback in visuomotor learning. Moreover, they suggest that the brain is able to account for such temporal associations in a flexible manner. PMID- 22666409 TI - Gender differences of brain activity in the conflicts based on implicit self esteem. AB - There are gender differences in global and domain-specific self-esteem and the incidence of some psychiatric disorders related to self-esteem, suggesting that there are gender differences in the neural basis underlying one's own self esteem. We investigated gender differences in the brain activity while subjects (14 males and 12 females) performed an implicit self-esteem task, using fMRI. While ventromedial prefrontal cortex (vmPFC) was significantly activated in females, medial and dorsomedial PFC (dmPFC) were activated in males in the incongruent condition (self = negative) compared with the congruent condition (self = positive). Additionally, scores on the explicit self-esteem test were negatively correlated with vmPFC activity in females and positively correlated with dmPFC activity in males. Furthermore, the functional relationships among the regions found by direct gender comparisons were discussed based on the somatic marker model. These showed that, compared to males, females more firmly store even the incongruent associations as part of their schematic self-knowledge, and such associations automatically activate the neural networks for emotional response and control, in which vmPFC plays a central role. This may explain female cognitive/behavioral traits; females have more tendency to ruminate more often than males, which sometimes results in a prolonged negative affect. PMID- 22666410 TI - River dolphins can act as population trend indicators in degraded freshwater systems. AB - Conservation attention on charismatic large vertebrates such as dolphins is often supported by the suggestion that these species represent surrogates for wider biodiversity, or act as indicators of ecosystem health. However, their capacity to act as indicators of patterns or trends in regional biodiversity has rarely been tested. An extensive new dataset of >300 last-sighting records for the Yangtze River dolphin or baiji and two formerly economically important fishes, the Yangtze paddlefish and Reeves' shad, all of which are probably now extinct in the Yangtze, was collected during an interview survey of fishing communities across the middle-lower Yangtze drainage. Untransformed last-sighting date frequency distributions for these species show similar decline curves over time, and the linear gradients of transformed last-sighting date series are not significantly different from each other, demonstrating that these species experienced correlated population declines in both timing and rate of decline. Whereas species may be expected to respond differently at the population level even in highly degraded ecosystems, highly vulnerable (e.g. migratory) species can therefore display very similar responses to extrinsic threats, even if they represent otherwise very different taxonomic, biological and ecological groupings. Monitoring the status of river dolphins or other megafauna therefore has the potential to provide wider information on the status of other threatened components of sympatric freshwater biotas, and so represents a potentially important monitoring tool for conservation management. We also show that interview surveys can provide robust quantitative data on relative population dynamics of different species. PMID- 22666411 TI - An X chromosome association scan of the Norfolk Island genetic isolate provides evidence for a novel migraine susceptibility locus at Xq12. AB - Migraine is a common and debilitating neurovascular disorder with a complex envirogenomic aetiology. Numerous studies have demonstrated a preponderance of women affected with migraine and previous pedigree linkage studies in our laboratory have identified susceptibility loci on chromosome Xq24-Xq28. In this study we have used the genetic isolate of Norfolk Island to further analyse the X chromosome for migraine susceptibility loci.An association approach was employed to analyse 14,124 SNPs spanning the entire X chromosome. Genotype data from 288 individuals comprising a large core-pedigree, of which 76 were affected with migraine, were analysed. Although no SNP reached chromosome-wide significance (empirical alpha = 1 * 10(-5)) ranking by P-value revealed two primary clusters of SNPs in the top 25. A 10 SNP cluster represents a novel migraine susceptibility locus at Xq12 whilst a 11 SNP cluster represents a previously identified migraine susceptibility locus at Xq27. The strongest association at Xq12 was seen for rs599958 (OR = 1.75, P = 8.92 * 10(-4)), whilst at Xq27 the strongest association was for rs6525667 (OR = 1.53, P = 1.65 * 10(-4)). Further analysis of SNPs at these loci was performed in 5,122 migraineurs from the Women's Genome Health Study and provided additional evidence for association at the novel Xq12 locus (P<0.05).Overall, this study provides evidence for a novel migraine susceptibility locus on Xq12. The strongest effect SNP (rs102834, joint P = 1.63 * 10(-5)) is located within the 5'UTR of the HEPH gene, which is involved in iron homeostasis in the brain and may represent a novel pathway for involvement in migraine pathogenesis. PMID- 22666412 TI - Stress-induced changes of hippocampal NMDA receptors: modulation by duloxetine treatment. AB - It is now well established that the glutamatergic system contributes to the pathophysiology of depression. Exposure to stress, a major precipitating factor for depression, enhances glutamate release that can contribute to structural abnormalities observed in the brain of depressed subjects. On the other hand, it has been demonstrated that NMDA antagonists, like ketamine, exert an antidepressant effect at preclinical and clinical levels. On these bases, the purpose of our study was to investigate whether chronic mild stress is associated with specific alterations of the NMDA receptor complex, in adult rats, and to establish whether concomitant antidepressant treatment could normalize such deficits. We found that chronic stress increases the expression of the obligatory GluN1 subunit, as well as of the accessory subunits GluN2A and GluN2B at transcriptional and translational levels, particularly in the ventral hippocampus. Concomitant treatment with the antidepressant duloxetine was able to normalize the increase of glutamatergic receptor subunit expression, and correct the changes in receptor phosphorylation produced by stress exposure. Our data suggest that prolonged stress, a condition that has etiologic relevance for depression, may enhance glutamate activity through post-synaptic mechanisms, by regulating NMDA receptors, and that antidepressants may in part normalize such changes. Our results provide support to the notion that antidepressants may exert their activity in the long-term also via modulation of the glutamatergic synapse. PMID- 22666414 TI - Household possession and use of insecticide-treated mosquito nets in Sierra Leone 6 months after a national mass-distribution campaign. AB - BACKGROUND: In November 2010, Sierra Leone distributed over three million long lasting insecticide-treated nets (LLINs) with the objective of providing protection from malaria to individuals in all households in the country. METHODS: We conducted a nationally representative survey six months after the mass distribution campaign to evaluate its impact on household insecticide-treated net (ITN) ownership and use. We examined factors associated with household ITN possession and use with logistic regression models. RESULTS: The survey included 4,620 households with equal representation in each of the 14 districts. Six months after the campaign, 87.6% of households own at least one ITN, which represents an increase of 137% over the most recent estimate of 37% in 2008. Thirty-six percent of households possess at least one ITN per two household members; rural households were more likely than urban households to have >= 1:2 ITN to household members, but there was no difference by socio-economic status or household head education. Among individuals in households possessing >= 1 ITN, 76.5% slept under an ITN the night preceding the survey. Individuals in households where the household head had heard malaria messaging, had correct knowledge of malaria transmission, and where at least one ITN was hanging, were more likely to have slept under an ITN. CONCLUSIONS: The mass distribution campaign was effective at achieving high coverage levels across the population, notably so among rural households where the malaria burden is higher. These important gains in equitable access to malaria prevention will need to be maintained to produce long-term reductions in the malaria burden. PMID- 22666413 TI - Flexibility in MuA transposase family protein structures: functional mapping with scanning mutagenesis and sequence alignment of protein homologues. AB - MuA transposase protein is a member of the retroviral integrase superfamily (RISF). It catalyzes DNA cleavage and joining reactions via an initial assembly and subsequent structural transitions of a protein-DNA complex, known as the Mu transpososome, ultimately attaching transposon DNA to non-specific target DNA. The transpososome functions as a molecular DNA-modifying machine and has been used in a wide variety of molecular biology and genetics/genomics applications. To analyze structure-function relationships in MuA action, a comprehensive pentapeptide insertion mutagenesis was carried out for the protein. A total of 233 unique insertion variants were generated, and their activity was analyzed using a quantitative in vivo DNA transposition assay. The results were then correlated with the known MuA structures, and the data were evaluated with regard to the protein domain function and transpososome development. To complement the analysis with an evolutionary component, a protein sequence alignment was produced for 44 members of MuA family transposases. Altogether, the results pinpointed those regions, in which insertions can be tolerated, and those where insertions are harmful. Most insertions within the subdomains Igamma, IIalpha, IIbeta, and IIIalpha completely destroyed the transposase function, yet insertions into certain loop/linker regions of these subdomains increased the protein activity. Subdomains Ialpha and IIIbeta were largely insertion-tolerant. The comprehensive structure-function data set will be useful for designing MuA transposase variants with improved properties for biotechnology/genomics applications, and is informative with regard to the function of RISF proteins in general. PMID- 22666415 TI - Prenatal famine and genetic variation are independently and additively associated with DNA methylation at regulatory loci within IGF2/H19. AB - Both the early environment and genetic variation may affect DNA methylation, which is one of the major molecular marks of the epigenome. The combined effect of these factors on a well-defined locus has not been studied to date. We evaluated the association of periconceptional exposure to the Dutch Famine of 1944-45, as an example of an early environmental exposure, and single nucleotide polymorphisms covering the genetic variation (tagging SNPs) with DNA methylation at the imprinted IGF2/H19 region, a model for an epigenetically regulated genomic region. DNA methylation was measured at five differentially methylated regions (DMRs) that regulate the imprinted status of the IGF2/H19 region. Small but consistent differences in DNA methylation were observed comparing 60 individuals with periconceptional famine exposure with unexposed same-sex siblings at all IGF2 DMRs (P(BH)<0.05 after adjustment for multiple testing), but not at the H19 DMR. IGF2 DMR0 methylation was associated with IGF2 SNP rs2239681 (P(BH) = 0.027) and INS promoter methylation with INS SNPs, including rs689, which tags the INS VNTR, suggesting a mechanism for the reported effect of the VNTR on INS expression (P(BH) = 3.4 * 10(-3)). Prenatal famine and genetic variation showed similar associations with IGF2/H19 methylation and their contributions were additive. They were small in absolute terms (<3%), but on average 0.5 standard deviations relative to the variation in the population. Our analyses suggest that environmental and genetic factors could have independent and additive similarly sized effects on DNA methylation at the same regulatory site. PMID- 22666416 TI - Biophysical characterization of the strong stabilization of the RNA triplex poly(U)*poly(A)*poly(U) by 9-O-(omega-amino) alkyl ether berberine analogs. AB - BACKGROUND: Binding of two 9-O-(omega-amino) alkyl ether berberine analogs BC1 and BC2 to the RNA triplex poly(U)(*)poly(A)(*)poly(U) was studied by various biophysical techniques. METHODOLOGY/PRINCIPAL FINDINGS: Berberine analogs bind to the RNA triplex non-cooperatively. The affinity of binding was remarkably high by about 5 and 15 times, respectively, for BC1 and BC2 compared to berberine. The site size for the binding was around 4.3 for all. Based on ferrocyanide quenching, fluorescence polarization, quantum yield values and viscosity results a strong intercalative binding of BC1 and BC2 to the RNA triplex has been demonstrated. BC1 and BC2 stabilized the Hoogsteen base paired third strand by about 18.1 and 20.5 degrees C compared to a 17.5 degrees C stabilization by berberine. The binding was entropy driven compared to the enthalpy driven binding of berbeine, most likely due to additional contacts within the grooves of the triplex and disruption of the water structure by the alkyl side chain. CONCLUSIONS/SIGNIFICANCE: Remarkably higher binding affinity and stabilization effect of the RNA triplex by the amino alkyl berberine analogs was achieved compared to berberine. The length of the alkyl side chain influence in the triplex stabilization phenomena. PMID- 22666417 TI - A high throughput screen identifies Nefopam as targeting cell proliferation in beta-catenin driven neoplastic and reactive fibroproliferative disorders. AB - Fibroproliferative disorders include neoplastic and reactive processes (e.g. desmoid tumor and hypertrophic scars). They are characterized by activation of beta-catenin signaling, and effective pharmacologic approaches are lacking. Here we undertook a high throughput screen using human desmoid tumor cell cultures to identify agents that would inhibit cell viability in tumor cells but not normal fibroblasts. Agents were then tested in additional cell cultures for an effect on cell proliferation, apoptosis, and beta-catenin protein level. Ultimately they were tested in Apc1638N mice, which develop desmoid tumors, as well as in wild type mice subjected to full thickness skin wounds. The screen identified Neofopam, as an agent that inhibited cell numbers to 42% of baseline in cell cultures from beta-catenin driven fibroproliferative disorders. Nefopam decreased cell proliferation and beta-catenin protein level to 50% of baseline in these same cell cultures. The half maximal effective concentration in-vitro was 0.5 uM and there was a plateau in the effect after 48 hours of treatment. Nefopam caused a 45% decline in tumor number, 33% decline in tumor volume, and a 40% decline in scar size when tested in mice. There was also a 50% decline in beta-catenin level in-vivo. Nefopam targets beta-catenin protein level in mesenchymal cells in-vitro and in-vivo, and may be an effective therapy for neoplastic and reactive processes driven by beta-catenin mediated signaling. PMID- 22666418 TI - Targeting melanoma metastasis and immunosuppression with a new mode of melanoma inhibitory activity (MIA) protein inhibition. AB - Melanoma is the most aggressive form of skin cancer, with fast progression and early dissemination mediated by the melanoma inhibitory activity (MIA) protein. Here, we discovered that dimerization of MIA is required for functional activity through mutagenesis of MIA which showed the correlation between dimerization and functional activity. We subsequently identified the dodecapeptide AR71, which prevents MIA dimerization and thereby acts as a MIA inhibitor. Two-dimensional nuclear magnetic resonance (NMR) spectroscopy demonstrated the binding of AR71 to the MIA dimerization domain, in agreement with in vitro and in vivo data revealing reduced cell migration, reduced formation of metastases and increased immune response after AR71 treatment. We believe AR71 is a lead structure for MIA inhibitors. More generally, inhibiting MIA dimerization is a novel therapeutic concept in melanoma therapy. PMID- 22666419 TI - Green tea polyphenol EGCG sensing motif on the 67-kDa laminin receptor. AB - BACKGROUND: We previously identified the 67-kDa laminin receptor (67LR) as the cell-surface receptor conferring the major green tea polyphenol (-) epigallocatechin-3-O-gallate (EGCG) responsiveness to cancer cells. However, the underlying mechanism for interaction between EGCG and 67LR remains unclear. In this study, we investigated the possible role of EGCG-67LR interaction responsible for its bioactivities. METHODOLOGY/PRINCIPAL FINDINGS: We synthesized various peptides deduced from the extracellular domain corresponding to the 102 295 region of human 67LR encoding a 295-amino acid. The neutralizing activity of these peptides toward EGCG cell-surface binding and inhibition of cancer cell growth were assayed. Both activities were inhibited by a peptide containing the 10-amino acid residues, IPCNNKGAHS, corresponding to residues 161-170. Furthermore, mass spectrometric analysis revealed the formation of a EGCG-LR161 170 peptide complex. A study of the amino acid deletion/replacement of the peptide LR161-170 indicated that the 10-amino acid length and two basic amino acids, K(166) and H(169), have a critical role in neutralizing EGCG's activities. Moreover, neutralizing activity against the anti-proliferation action of EGCG was observed in a recombinant protein of the extracellular domain of 67LR, and this effect was abrogated by a deletion of residues 161-170. These findings support that the 10 amino-acid sequence, IPCNNKGAHS, might be the functional domain responsible for the anti-cancer activity of EGCG. CONCLUSIONS/SIGNIFICANCE: Overall, our results highlight the nature of the EGCG-67LR interaction and provide novel structural insights into the understanding of 67LR-mediated functions of EGCG, and could aid in the development of potential anti-cancer compounds for chemopreventive or therapeutic uses that can mimic EGCG-67LR interactions. PMID- 22666420 TI - 8q24 Cancer risk allele associated with major metastatic risk in inflammatory breast cancer. AB - BACKGROUND: Association studies have identified low penetrance alleles that participate to the risk of cancer development. The 8q24 chromosomal region contains several such loci involved in various cancers that have been recently studied for their propensity to influence the clinical outcome of prostate cancer. We investigated here two 8q24 breast and colon cancer risk alleles in the close vicinity of the MYC gene for their role in the occurrence of distant metastases. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective series of 449 patients affected with breast or colon adenocarcinoma was genotyped for the rs13281615 and/or rs6983267 SNPs. Statistical analyses were done using the survival package v2.30 in the R software v2.9.1. The two SNPs did not influence the development of distant metastases of colon cancer; rs6983267 showed a mild effect on breast cancer. However, this effect was greatly emphasized when considering inflammatory breast cancer (IBC) solely. Replicated on a larger and independent series of IBC the contribution of the genotype to the metastatic risk of IBC was found an independent predictor of outcome (p = 2e-4; OR 8.3, CI95:2.6 33). CONCLUSIONS/SIGNIFICANCE: Our study shows first that the monitoring of this specific germline variation may add a substantial tool for IBC prognostication, an aggressive disease that evolves towards distant metastases much more frequently than non-IBC and for which no reliable prognostic factor is available in medical practice. Second, it more generally suggests that risk alleles, while associated with low susceptibility, could correlate with a high risk of metastasis. PMID- 22666421 TI - Spare PRELI gene loci: failsafe chromosome insurance? AB - BACKGROUND: LEA (late embryogenesis abundant) proteins encode conserved N terminal mitochondrial signal domains and C-terminal (A/TAEKAK) motif repeats, long-presumed to confer cell resistance to stress and death cues. This prompted the hypothesis that LEA proteins are central to mitochondria mechanisms that connect bioenergetics with cell responses to stress and death signaling. In support of this hypothesis, recent studies have demonstrated that mammalian LEA protein PRELI can act as a biochemical hub, which upholds mitochondria energy metabolism, while concomitantly promoting B cell resistance to stress and induced death. Hence, it is important to define in vivo the physiological relevance of PRELI expression. METHODS AND FINDINGS: Given the ubiquitous PRELI expression during mouse development, embryo lethality could be anticipated. Thus, conditional gene targeting was engineered by insertion of flanking loxP (flox)/Cre recognition sites on PRELI chromosome 13 (Chr 13) locus to abort its expression in a tissue-specific manner. After obtaining mouse lines with homozygous PRELI floxed alleles (PRELI(f/f)), the animals were crossed with CD19 driven Cre-recombinase transgenic mice to investigate whether PRELI inactivation could affect B-lymphocyte physiology and survival. Mice with homozygous B cell specific PRELI deletion (CD19-Cre/Chr13 PRELI(-/-)) bred normally and did not show any signs of morbidity. Histopathology and flow cytometry analyses revealed that cell lineage identity, morphology, and viability were indistinguishable between wild type CD19-Cre/Chr13 PRELI(+/+) and CD19-Cre/Chr13 PRELI(-/-) deficient mice. Furthermore, B cell PRELI gene expression seemed unaffected by Chr13 PRELI gene targeting. However, identification of additional PRELI loci in mouse Chr1 and Chr5 provided an explanation for the paradox between LEA-dependent cytoprotection and the seemingly futile consequences of Chr 13 PRELI gene inactivation. Importantly, PRELI expression from spare gene loci appeared ample to surmount Chr 13 PRELI gene deficiency. CONCLUSIONS: These findings suggest that PRELI is a vital LEA B cell protein with failsafe genetics. PMID- 22666422 TI - Genome-wide characterization of menin-dependent H3K4me3 reveals a specific role for menin in the regulation of genes implicated in MEN1-like tumors. AB - Inactivating mutations in the MEN1 gene predisposing to the multiple endocrine neoplasia type 1 (MEN1) syndrome can also cause sporadic pancreatic endocrine tumors. MEN1 encodes menin, a subunit of MLL1/MLL2-containing histone methyltransferase complexes that trimethylate histone H3 at lysine 4 (H3K4me3). The importance of menin-dependent H3K4me3 in normal and transformed pancreatic endocrine cells is unclear. To study the role of menin-dependent H3K4me3, we performed in vitro differentiation of wild-type as well as menin-null mouse embryonic stem cells (mESCs) into pancreatic islet-like endocrine cells (PILECs). Gene expression analysis and genome-wide H3K4me3 ChIP-Seq profiling in wild-type and menin-null mESCs and PILECs revealed menin-dependent H3K4me3 at the imprinted Dlk1-Meg3 locus in mESCs, and all four Hox loci in differentiated PILECs. Specific and significant loss of H3K4me3 and gene expression was observed for genes within the imprinted Dlk1-Meg3 locus in menin-null mESCs and the Hox loci in menin-null PILECs. Given that the reduced expression of genes within the DLK1 MEG3 locus and the HOX loci is associated with MEN1-like sporadic tumors, our data suggests a possible role for menin-dependent H3K4me3 at these genes in the initiation and progression of sporadic pancreatic endocrine tumors. Furthermore, our investigation also demonstrates that menin-null mESCs can be differentiated in vitro into islet-like endocrine cells, underscoring the utility of menin-null mESC-derived specialized cell types for genome-wide high-throughput studies. PMID- 22666423 TI - ADP-ribosylation factor 6 expression and activation are reduced in myometrium in complicated pregnancies. AB - BACKGROUND: ARF6 (ADP-ribosylation factor 6) small GTP binding protein plays critical roles in actin cytoskeleton rearrangements and membrane trafficking, including internalisation of G protein coupled receptors (GPCR). ARF6 operates by cycling between GDP-bound (inactive) and GTP-bound (active) forms and is a potential regulator of GPCR-mediated uterine activity during pregnancy and labour. ARF6 contains very low intrinsic GTP binding activity and depends on GEFs (guanine nucleotide exchange factors) such as CYTH3 (cytohesin 3) to bind GTP. ARF6 and CYTH3 were originally cloned from human placenta, but there is no information on their expression in other reproductive tissues. METHODS: The expression of ARF6, ARF1, and CYTH1-4 was investigated by measuring mRNA (using RT-PCR) and protein levels (using immunoblotting) in samples of myometrium obtained from non-pregnant women, and women with normal pregnancies, before or after the spontaneous onset of labour. We also analysed myometrial samples from women with spontaneous preterm labour and from women with complicated pregnancies requiring emergency preterm delivery. The GST)-effector pull down assay was used to study the presence of active ARF6 and ARF1 in all myometrial extracts. RESULTS: ARF6, ARF1 and CYTH3 but not CYTH1, CYTH2 and CYTH4 were expressed in all samples and the levels did not change with pregnancy or labour. However, ARF6 and CYTH3 but not ARF1 levels were significantly reduced in complicated pregnancies. The alterations in the expression of ARF6 and its GEF in human myometrium indicate a potential involvement of this signalling system in modulating the response of myometrial smooth muscle in complicated pregnancies. The levels of ARF6-GTP or ARF1-GTP did not change with pregnancy or labour but ARF6-GTP levels were significantly decreased in women with severe complications of pregnancy. CONCLUSIONS: We have demonstrated a functional ARF6 system in human myometrium and a correlation between ARF6 level and activity in uterine and abnormal pregnancy. PMID- 22666424 TI - Believing and perceiving: authorship belief modulates sensory attenuation. AB - Sensory attenuation refers to the observation that self-generated stimuli are attenuated, both in terms of their phenomenology and their cortical response compared to the same stimuli when generated externally. Accordingly, it has been assumed that sensory attenuation might help individuals to determine whether a sensory event was caused by themselves or not. In the present study, we investigated whether this dependency is reciprocal, namely whether sensory attenuation is modulated by prior beliefs of authorship. Participants had to judge the loudness of auditory effects that they believed were either self generated or triggered by another person. However, in reality, the sounds were always triggered by the participants' actions. Participants perceived the tones' loudness attenuated when they believed that the sounds were self-generated compared to when they believed that they were generated by another person. Sensory attenuation is considered to contribute to the emergence of people's belief of authorship. Our results suggest that sensory attenuation is also a consequence of prior belief about the causal link between an action and a sensory change in the environment. PMID- 22666425 TI - Do musicians with perfect pitch have more autism traits than musicians without perfect pitch? An empirical study. AB - Perfect pitch, also known as absolute pitch (AP), refers to the rare ability to identify or produce a musical tone correctly without the benefit of an external reference. AP is often considered to reflect musical giftedness, but it has also been associated with certain disabilities due to increased prevalence of AP in individuals with sensory and developmental disorders. Here, we determine whether individual autistic traits are present in people with AP. We quantified subclinical levels of autism traits using the Autism-Spectrum Quotient (AQ) in three matched groups of subjects: 16 musicians with AP (APs), 18 musicians without AP (non-APs), and 16 non-musicians. In addition, we measured AP ability by a pitch identification test with sine wave tones and piano tones. We found a significantly higher degree of autism traits in APs than in non-APs and non musicians, and autism scores were significantly correlated with pitch identification scores (r = .46, p = .003). However, our results showed that APs did not differ from non-APs on diagnostically crucial social and communicative domain scores and their total AQ scores were well below clinical thresholds for autism. Group differences emerged on the imagination and attention switching subscales of the AQ. Thus, whilst these findings do link AP with autism, they also show that AP ability is most strongly associated with personality traits that vary widely within the normal population. PMID- 22666426 TI - Experimental inoculation of juvenile rhesus macaques with primate enteric caliciviruses. AB - BACKGROUND: Tissue culture-adapted Tulane virus (TV), a GI.1 rhesus enteric calicivirus (ReCV), and a mixture of GII.2 and GII.4 human norovirus (NoV) containing stool sample were used to intrastomacheally inoculate juvenile rhesus macaques (Macaca mulatta) in order to evaluate infection caused by these viruses. METHODOLOGY & FINDINGS: Two of the three TV-inoculated macaques developed diarrhea, fever, virus-shedding in stools, inflammation of duodenum and 16-fold increase of TV-neutralizing (VN) serum antibodies but no vomiting or viremia. No VN-antibody responses could be detected against a GI.2 ReCV strain FT285, suggesting that TV and FT285 represent different ReCV serotypes. Both NoV inoculated macaques remained asymptomatic but with demonstrable virus shedding in one animal. Examination of duodenum biopsies of the TV-inoculated macaques showed lymphocytic infiltration of the lamina propria and villous blunting. TV antigen positive (TV+) cells were detected in the lamina propria. In most of the TV+ cells TV co-localized perinuclearly with calnexin--an endoplasmic reticulum protein. A few CD20+TV+ double-positive B cells were also identified in duodenum. To corroborate the authenticity of CD20+TV+ B cells, in vitro cultures of peripheral blood mononuclear cells (PBMCs) from healthy macaques were inoculated with TV. Multicolor flow cytometry confirmed the presence of TV antigen containing B cells of predominantly CD20+HLA-DR+ phenotype. A 2-log increase of viral RNA by 6 days post inoculation (p<0.05) suggested active TV replication in cultured lymphocytes. CONCLUSIONS/SIGNIFICANCE: Taken together, our results show that ReCVs represent an alternative cell culture and animal model to study enteric calicivirus replication, pathogenesis and immunity. PMID- 22666427 TI - Modelling the genetic risk in age-related macular degeneration. AB - Late-stage age-related macular degeneration (AMD) is a common sight-threatening disease of the central retina affecting approximately 1 in 30 Caucasians. Besides age and smoking, genetic variants from several gene loci have reproducibly been associated with this condition and likely explain a large proportion of disease. Here, we developed a genetic risk score (GRS) for AMD based on 13 risk variants from eight gene loci. The model exhibited good discriminative accuracy, area under-curve (AUC) of the receiver-operating characteristic of 0.820, which was confirmed in a cross-validation approach. Noteworthy, younger AMD patients aged below 75 had a significantly higher mean GRS (1.87, 95% CI: 1.69-2.05) than patients aged 75 and above (1.45, 95% CI: 1.36-1.54). Based on five equally sized GRS intervals, we present a risk classification with a relative AMD risk of 64.0 (95% CI: 14.11-1131.96) for individuals in the highest category (GRS 3.44-5.18, 0.5% of the general population) compared to subjects with the most common genetic background (GRS -0.05-1.70, 40.2% of general population). The highest GRS category identifies AMD patients with a sensitivity of 7.9% and a specificity of 99.9% when compared to the four lower categories. Modeling a general population around 85 years of age, 87.4% of individuals in the highest GRS category would be expected to develop AMD by that age. In contrast, only 2.2% of individuals in the two lowest GRS categories which represent almost 50% of the general population are expected to manifest AMD. Our findings underscore the large proportion of AMD cases explained by genetics particularly for younger AMD patients. The five category risk classification could be useful for therapeutic stratification or for diagnostic testing purposes once preventive treatment is available. PMID- 22666428 TI - Genetic analyses of heme oxygenase 1 (HMOX1) in different forms of pancreatitis. AB - BACKGROUND: Heme oxygenase 1 (HMOX1) is the rate limiting enzyme in heme degradation and a key regulator of inflammatory processes. In animal models the course of pancreatitis was ameliorated by up-regulation of HMOX1 expression. Additionally, carbon monoxide released during heme breakdown inhibited proliferation of pancreatic stellate cells and might thereby prevent the development of chronic pancreatitis (CP). Transcription of HMOX1 in humans is influenced by a GT-repeat located in the promoter. As such, HMOX1 variants might be of importance in the pathogenesis of pancreatitis. METHODS: The GT-repeat and SNP rs2071746 were investigated with fluorescence labelled primers and by melting curve analysis in 285 patients with acute pancreatitis, 208 patients with alcoholic CP, 207 patients with idiopathic/hereditary CP, 147 patients with alcoholic liver cirrhosis, and in 289 controls, respectively. GT-repeat analysis was extended to a total of 446 alcoholic CP patients. In addition, we performed DNA sequencing in 145 patients with alcoholic CP, 138 patients with idiopathic/hereditary CP, 147 patients with alcoholic liver cirrhosis, and 151 controls. Exon 3 screening was extended to additional patients and controls. RESULTS: S- and L-alleles of the GT-repeat, genotypes and alleles of SNP rs2071746 and non-synonymous variants detected by sequencing were found with similar frequencies in all groups. CONCLUSIONS: Although functional data implicate a potential influence of HMOX1 variants on the pathogenesis of pancreatitis, we did not find any association. As rare non-synonymous HMOX1 variants were found in patients and controls, it is rather unlikely that they will have functional consequences essential for pancreatitis development. PMID- 22666429 TI - FOX-2 dependent splicing of ataxin-2 transcript is affected by ataxin-1 overexpression. AB - Alternative splicing is a fundamental posttranscriptional mechanism for controlling gene expression, and splicing defects have been linked to various human disorders. The splicing factor FOX-2 is part of a main protein interaction hub in a network related to human inherited ataxias, however, its impact remains to be elucidated. Here, we focused on the reported interaction between FOX-2 and ataxin-1, the disease-causing protein in spinocerebellar ataxia type 1. In this line, we further evaluated this interaction by yeast-2-hybrid analyses and co immunoprecipitation experiments in mammalian cells. Interestingly, we discovered that FOX-2 localization and splicing activity is affected in the presence of nuclear ataxin-1 inclusions. Moreover, we observed that FOX-2 directly interacts with ataxin-2, a protein modulating spinocerebellar ataxia type 1 pathogenesis. Finally, we provide evidence that splicing of pre-mRNA of ataxin-2 depends on FOX 2 activity, since reduction of FOX-2 levels led to increased skipping of exon 18 in ataxin-2 transcripts. Most striking, we observed that ataxin-1 overexpression has an effect on this splicing event as well. Thus, our results demonstrate that FOX-2 is involved in splicing of ataxin-2 transcripts and that this splicing event is altered by overexpression of ataxin-1. PMID- 22666430 TI - Relation of IL28B gene polymorphism with biochemical and histological features in hepatitis C virus-induced liver disease. AB - BACKGROUND/AIMS: Polymorphism at the IL28B gene may modify the course of hepatitis C virus (HCV) chronic infection. Our aim was to study the influence of IL28B rs12979860 gene polymorphism on the biochemistry and pathology of HCV induced disease in the clinical course from mild chronic hepatitis C to hepatocellular carcinoma. METHODS: We have determined the rs12979860 single nucleotide polymorphism (SNP) upstream IL28B gene in two groups of patients with HCV-induced chronic liver disease: 1) 268 patients (159 men) with biopsy-proven chronic hepatitis C, to analyse its relation with biochemical, virological and histological features; and 2) 134 patients (97 men) with HCV-related hepatocellular carcinoma. The distribution of the analysed SNP in hepatocellular carcinoma patients was compared with that found in untreated chronic hepatitis C patients. All patients were white and most were Spaniards. RESULTS: In multivariate analysis ALT values were higher (P = 0.001) and GGT values were lower (P<0.001) in chronic hepatitis C patients homozygotes for the major rs12979860C allele as compared with carriers of the mutated rs12979860T allele. Steatosis was more frequent (Odds ratio = 1.764, 95% C.I. 1.053-2.955) and severe (P = 0.026) in carriers of the rs12979860T allele. No relation was found between the analysed SNP and METAVIR scores for necroinflammation and fibrosis, and there were no differences in the distribution of the analysed SNP between hepatocellular carcinoma and untreated chronic hepatitis C patients. CONCLUSION: The IL28B rs12979860 polymorphism correlates with the biochemical activity and the presence and severity of liver steatosis in chronic hepatitis C. PMID- 22666431 TI - Retigeric acid B exhibits antitumor activity through suppression of nuclear factor-kappaB signaling in prostate cancer cells in vitro and in vivo. AB - Previously, we reported that retigeric acid B (RB), a natural pentacyclic triterpenic acid isolated from lichen, inhibited cell growth and induced apoptosis in androgen-independent prostate cancer (PCa) cells. However, the mechanism of action of RB remains unclear. In this study, we found that using PC3 and DU145 cells as models, RB inhibited phosphorylation levels of IkappaBalpha and p65 subunit of NF-kappaB in a time- and dosage-dependent manner. Detailed study revealed that RB blocked the nuclear translocation of p65 and its DNA binding activity, which correlated with suppression of NF-kappaB-regulated proteins including Bcl-2, Bcl-x(L), cyclin D1 and survivin. NF-kappaB reporter assay suggested that RB was able to inhibit both constitutive activated-NF-kappaB and LPS (lipopolysaccharide)-induced activation of NF-kappaB. Overexpression of RelA/p65 rescued RB-induced cell death, while knockdown of RelA/p65 significantly promoted RB-mediated inhibitory effect on cell proliferation, suggesting the crucial involvement of NF-kappaB pathway in this event. We further analyzed antitumor activity of RB in in vivo study. In C57BL/6 mice carrying RM-1 homografts, RB inhibited tumor growth and triggered apoptosis mainly through suppressing NF-kappaB activity in tumor tissues. Additionally, DNA microarray data revealed global changes in the gene expression associated with cell proliferation, apoptosis, invasion and metastasis in response to RB treatment. Therefore, our findings suggested that RB exerted its anti-tumor effect by targeting the NF-kappaB pathway in PCa cells, and this could be a general mechanism for the anti-tumor effect of RB in other types of cancers as well. PMID- 22666432 TI - Between a rock and a hard place: habitat selection in female-calf humpback whale (Megaptera novaeangliae) Pairs on the Hawaiian breeding grounds. AB - The Au'au Channel between the islands of Maui and Lanai, Hawaii comprises critical breeding habitat for humpback whales (Megaptera novaeangliae) of the Central North Pacific stock. However, like many regions where marine mega-fauna gather, these waters are also the focus of a flourishing local eco-tourism and whale watching industry. Our aim was to establish current trends in habitat preference in female-calf humpback whale pairs within this region, focusing specifically on the busy, eastern portions of the channel. We used an equally spaced zigzag transect survey design, compiled our results in a GIS model to identify spatial trends and calculated Neu's Indices to quantify levels of habitat use. Our study revealed that while mysticete female-calf pairs on breeding grounds typically favor shallow, inshore waters, female-calf pairs in the Au'au Channel avoided shallow waters (<20 m) and regions within 2 km of the shoreline. Preferred regions for female-calf pairs comprised water depths between 40-60 m, regions of rugged bottom topography and regions that lay between 4 and 6 km from a small boat harbor (Lahaina Harbor) that fell within the study area. In contrast to other humpback whale breeding grounds, there was only minimal evidence of typical patterns of stratification or segregation according to group composition. A review of habitat use by maternal females across Hawaiian waters indicates that maternal habitat choice varies between localities within the Hawaiian Islands, suggesting that maternal females alter their use of habitat according to locally varying pressures. This ability to respond to varying environments may be the key that allows wildlife species to persist in regions where human activity and critical habitat overlap. PMID- 22666433 TI - Hierarchical multi-species modeling of carnivore responses to hunting, habitat and prey in a West African protected area. AB - Protected areas (PAs) are a cornerstone of global efforts to shield wildlife from anthropogenic impacts, yet their effectiveness at protecting wide-ranging species prone to human conflict--notably mammalian carnivores--is increasingly in question. An understanding of carnivore responses to human-induced and natural changes in and around PAs is critical not only to the conservation of threatened carnivore populations, but also to the effective protection of ecosystems in which they play key functional roles. However, an important challenge to assessing carnivore communities is the often infrequent and imperfect nature of survey detections. We applied a novel hierarchical multi-species occupancy model that accounted for detectability and spatial autocorrelation to data from 224 camera trap stations (sampled between October 2006 and January 2009) in order to test hypotheses about extrinsic influences on carnivore community dynamics in a West African protected area (Mole National Park, Ghana). We developed spatially explicit indices of illegal hunting activity, law enforcement patrol effort, prey biomass, and habitat productivity across the park, and used a Bayesian model selection framework to identify predictors of site occurrence for individual species and the entire carnivore community. Contrary to our expectation, hunting pressure and edge proximity did not have consistent, negative effects on occurrence across the nine carnivore species detected. Occurrence patterns for most species were positively associated with small prey biomass, and several species had either positive or negative associations with riverine forest (but not with other habitat descriptors). Influences of sampling design on carnivore detectability were also identified and addressed within our modeling framework (e.g., road and observer effects), and the multi-species approach facilitated inference on even the rarest carnivore species in the park. Our study provides insight for the conservation of these regionally significant carnivore populations, and our approach is broadly applicable to the robust assessment of communities of rare and elusive species subject to environmental change. PMID- 22666434 TI - Localization of the Drosophila Rad9 protein to the nuclear membrane is regulated by the C-terminal region and is affected in the meiotic checkpoint. AB - Rad9, Rad1, and Hus1 (9-1-1) are part of the DNA integrity checkpoint control system. It was shown previously that the C-terminal end of the human Rad9 protein, which contains a nuclear localization sequence (NLS) nearby, is critical for the nuclear transport of Rad1 and Hus1. In this study, we show that in Drosophila, Hus1 is found in the cytoplasm, Rad1 is found throughout the entire cell and that Rad9 (DmRad9) is a nuclear protein. More specifically, DmRad9 exists in two alternatively spliced forms, DmRad9A and DmRad9B, where DmRad9B is localized at the cell nucleus, and DmRad9A is found on the nuclear membrane both in Drosophila tissues and also when expressed in mammalian cells. Whereas both alternatively spliced forms of DmRad9 contain a common NLS near the C terminus, the 32 C-terminal residues of DmRad9A, specific to this alternative splice form, are required for targeting the protein to the nuclear membrane. We further show that activation of a meiotic checkpoint by a DNA repair gene defect but not defects in the anchoring of meiotic chromosomes to the oocyte nuclear envelope upon ectopic expression of non-phosphorylatable Barrier to Autointegration Factor (BAF) dramatically affects DmRad9A localization. Thus, by studying the localization pattern of DmRad9, our study reveals that the DmRad9A C-terminal region targets the protein to the nuclear membrane, where it might play a role in response to the activation of the meiotic checkpoint. PMID- 22666435 TI - Coauthorship and institutional collaborations on cost-effectiveness analyses: a systematic network analysis. AB - BACKGROUND: Cost-Effectiveness Analysis (CEA) has been promoted as an important research methodology for determining the efficiency of healthcare technology and guiding medical decision-making. Our aim was to characterize the collaborative patterns of CEA conducted over the past two decades in Spain. METHODS AND FINDINGS: A systematic analysis was carried out with the information obtained through an updated comprehensive literature review and from reports of health technology assessment agencies. We identified CEAs with outcomes expressed as a time-based summary measure of population health (e.g. quality-adjusted life-years or disability-adjusted life-years), conducted in Spain and published between 1989 and 2011. Networks of coauthorship and institutional collaboration were produced using PAJEK software. One-hundred and thirty-one papers were analyzed, in which 526 authors and 230 institutions participated. The overall signatures per paper index was 5.4. Six major groups (one with 14 members, three with 7 members and two with 6 members) were identified. The most prolific authors were generally affiliated with the private-for-profit sector (e.g. consulting firms and the pharmaceutical industry). The private-for-profit sector maintains profuse collaborative networks including public hospitals and academia. Collaboration within the public sector (e.g. healthcare administration and primary care) was weak and fragmented. CONCLUSIONS: This empirical analysis reflects critical practices among collaborative networks that contributed substantially to the production of CEA, raises challenges for redesigning future policies and provides a framework for similar analyses in other regions. PMID- 22666437 TI - Weight gain is associated with medial contact site of subthalamic stimulation in Parkinson's disease. AB - The aim of our study was to assess changes in body-weight in relation to active electrode contact position in the subthalamic nucleus. Regular body weight measurements were done in 20 patients with advanced Parkinson's disease within a period of 18 months after implantation. T1-weighted (1.5T) magnetic resonance images were used to determine electrode position in the subthalamic nucleus and the Unified Parkinson's disease rating scale (UPDRS-III) was used for motor assessment. The distance of the contacts from the wall of the third ventricle in the mediolateral direction inversely correlated with weight gain (r = -0.55, p<0.01) and with neurostimulation-related motor condition expressed as the contralateral hemi-body UPDRS-III (r = -0.42, p<0.01). Patients with at least one contact within 9.3 mm of the wall experienced significantly greater weight gain (9.4 +/- (SD)4.4 kg, N = 11) than those with both contacts located laterally (3.9 +/- 2.7 kg, N = 9) (p<0.001). The position of the active contact is critical not only for motor outcome but is also associated with weight gain, suggesting a regional effect of subthalamic stimulation on adjacent structures involved in the central regulation of energy balance, food intake or reward. PMID- 22666436 TI - 1B/(-)IRE DMT1 expression during brain ischemia contributes to cell death mediated by NF-kappaB/RelA acetylation at Lys310. AB - The molecular mechanisms responsible for increasing iron and neurodegeneration in brain ischemia are an interesting area of research which could open new therapeutic approaches. Previous evidence has shown that activation of nuclear factor kappa B (NF-kappaB) through RelA acetylation on Lys310 is the prerequisite for p50/RelA-mediated apoptosis in cellular and animal models of brain ischemia. We hypothesized that the increase of iron through a NF-kappaB-regulated 1B isoform of the divalent metal transporter-1 (1B/DMT1) might contribute to post ischemic neuronal damage. Both in mice subjected to transient middle cerebral artery occlusion (MCAO) and in neuronally differentiated SK-N-SH cells exposed to oxygen-glucose-deprivation (OGD), 1A/DMT1 was only barely expressed while the 1B/DMT1 without iron-response-element (-IRE) protein and mRNA were early up regulated. Either OGD or over-expression of 1B/(-)IRE DMT1 isoform significantly increased iron uptake, as detected by total reflection X-ray fluorescence, and iron-dependent cell death. Iron chelation by deferoxamine treatment or (-)IRE DMT1 RNA silencing displayed significant neuroprotection against OGD which concomitantly decreased intracellular iron levels. We found evidence that 1B/( )IRE DMT1 was a target gene for RelA activation and acetylation on Lys310 residue during ischemia. Chromatin immunoprecipitation analysis of the 1B/DMT1 promoter showed there was increased interaction with RelA and acetylation of H3 histone during OGD exposure of cortical neurons. Over-expression of wild-type RelA increased 1B/DMT1 promoter-luciferase activity, the (-)IRE DMT1 protein, as well as neuronal death. Expression of the acetylation-resistant RelA-K310R construct, which carried a mutation from lysine 310 to arginine, but not the acetyl-mimic mutant RelA-K310Q, down-regulated the 1B/DMT1 promoter, consequently offering neuroprotection. Our data showed that 1B/(-)IRE DMT1 expression and intracellular iron influx are early downstream responses to NF-kappaB/RelA activation and acetylation during brain ischemia and contribute to the pathogenesis of stroke induced neuronal damage. PMID- 22666438 TI - What was I thinking? Eye-tracking experiments underscore the bias that architecture exerts on nuclear grading in prostate cancer. AB - We previously reported that nuclear grade assignment of prostate carcinomas is subject to a cognitive bias induced by the tumor architecture. Here, we asked whether this bias is mediated by the non-conscious selection of nuclei that "match the expectation" induced by the inadvertent glance at the tumor architecture. 20 pathologists were asked to grade nuclei in high power fields of 20 prostate carcinomas displayed on a computer screen. Unknown to the pathologists, each carcinoma was shown twice, once before a background of a low grade, tubule-rich carcinoma and once before the background of a high grade, solid carcinoma. Eye tracking allowed to identify which nuclei the pathologists fixated during the 8 second projection period. For all 20 pathologists, nuclear grade assignment was significantly biased by tumor architecture. Pathologists tended to fixate on bigger, darker, and more irregular nuclei when those were projected before kigh grade, solid carcinomas than before low grade, tubule-rich carcinomas (and vice versa). However, the morphometric differences of the selected nuclei accounted for only 11% of the architecture-induced bias, suggesting that it can only to a small part be explained by the unconscious fixation on nuclei that "match the expectation". In conclusion, selection of " matching nuclei " represents an unconscious effort to vindicate the gravitation of nuclear grades towards the tumor architecture. PMID- 22666439 TI - Fractionation of a herbal antidiarrheal medicine reveals eugenol as an inhibitor of Ca2+-Activated Cl- channel TMEM16A. AB - The Ca(2+)-activated Cl(-) channel TMEM16A is involved in epithelial fluid secretion, smooth muscle contraction and neurosensory signaling. We identified a Thai herbal antidiarrheal formulation that inhibited TMEM16A Cl(-) conductance. C18-reversed-phase HPLC fractionation of the herbal formulation revealed >98% of TMEM16A inhibition activity in one out of approximately 20 distinct peaks. The purified, active compound was identified as eugenol (4-allyl-2-methoxyphenol), the major component of clove oil. Eugenol fully inhibited TMEM16A Cl(-) conductance with single-site IC(50)~150 uM. Eugenol inhibition of TMEM16A in interstitial cells of Cajal produced strong inhibition of intestinal contraction in mouse ileal segments. TMEM16A Cl(-) channel inhibition adds to the list of eugenol molecular targets and may account for some of its biological activities. PMID- 22666440 TI - Ubiquitous [Na+]i/[K+]i-sensitive transcriptome in mammalian cells: evidence for Ca(2+)i-independent excitation-transcription coupling. AB - Stimulus-dependent elevation of intracellular Ca(2+) ([Ca(2+)](i)) affects the expression of numerous genes--a phenomenon known as excitation-transcription coupling. Recently, we found that increases in [Na(+)](i) trigger c-Fos expression via a novel Ca(2+) (i)-independent pathway. In the present study, we identified ubiquitous and tissue-specific [Na(+)](i)/[K(+)](i)-sensitive transcriptomes by comparative analysis of differentially expressed genes in vascular smooth muscle cells from rat aorta (RVSMC), the human adenocarcinoma cell line HeLa, and human umbilical vein endothelial cells (HUVEC). To augment [Na(+)](i) and reduce [K(+)](i), cells were treated for 3 hrs with the Na(+),K(+) ATPase inhibitor ouabain or placed for the same time in the K(+)-free medium. Employing Affymetrix-based technology, we detected changes in expression levels of 684, 737 and 1839 transcripts in HeLa, HUVEC and RVSMC, respectively, that were highly correlated between two treatments (p<0.0001; R(2)>0.62). Among these Na(+) (i)/K(+) (i)-sensitive genes, 80 transcripts were common for all three types of cells. To establish if changes in gene expression are dependent on increases in [Ca(2+)](i), we performed identical experiments in Ca(2+)-free media supplemented with extracellular and intracellular Ca(2+) chelators. Surprisingly, this procedure elevated rather than decreased the number of ubiquitous and cell type specific Na(+) (i)/K(+) (i)-sensitive genes. Among the ubiquitous Na(+) (i)/K(+) (i)-sensitive genes whose expression was regulated independently of the presence of Ca(2+) chelators by more than 3-fold, we discovered several transcription factors (Fos, Jun, Hes1, Nfkbia), interleukin-6, protein phosphatase 1 regulatory subunit, dual specificity phosphatase (Dusp8), prostaglandin-endoperoxide synthase 2, cyclin L1, whereas expression of metallopeptidase Adamts1, adrenomedulin, Dups1, Dusp10 and Dusp16 was detected exclusively in Ca(2+)-depleted cells. Overall, our findings indicate that Ca(2+) (i)-independent mechanisms of excitation-transcription coupling are involved in transcriptomic alterations triggered by elevation of the [Na(+)](i)/[K(+)](i) ratio. There results likely have profound implications for normal and pathological regulation of mammalian cells, including sustained excitation of neuronal cells, intensive exercise and ischemia-triggered disorders. PMID- 22666441 TI - Lack of correlation between outcomes of membrane repair assay and correction of dystrophic changes in experimental therapeutic strategy in dysferlinopathy. AB - Mutations in the dysferlin gene are the cause of Limb-girdle Muscular Dystrophy type 2B and Miyoshi Myopathy. The dysferlin protein has been implicated in sarcolemmal resealing, leading to the idea that the pathophysiology of dysferlin deficiencies is due to a deficit in membrane repair. Here, we show using two different approaches that fulfilling membrane repair as asseyed by laser wounding assay is not sufficient for alleviating the dysferlin deficient pathology. First, we generated a transgenic mouse overexpressing myoferlin to test the hypothesis that myoferlin, which is homologous to dysferlin, can compensate for the absence of dysferlin. The myoferlin overexpressors show no skeletal muscle abnormalities, and crossing them with a dysferlin-deficient model rescues the membrane fusion defect present in dysferlin-deficient mice in vitro. However, myoferlin overexpression does not correct muscle histology in vivo. Second, we report that AAV-mediated transfer of a minidysferlin, previously shown to correct the membrane repair deficit in vitro, also fails to improve muscle histology. Furthermore, neither myoferlin nor the minidysferlin prevented myofiber degeneration following eccentric exercise. Our data suggest that the pathogenicity of dysferlin deficiency is not solely related to impairment in sarcolemmal repair and highlight the care needed in selecting assays to assess potential therapies for dysferlinopathies. PMID- 22666442 TI - Phylogenetic analysis of a spontaneous cocoa bean fermentation metagenome reveals new insights into its bacterial and fungal community diversity. AB - This is the first report on the phylogenetic analysis of the community diversity of a single spontaneous cocoa bean box fermentation sample through a metagenomic approach involving 454 pyrosequencing. Several sequence-based and composition based taxonomic profiling tools were used and evaluated to avoid software dependent results and their outcome was validated by comparison with previously obtained culture-dependent and culture-independent data. Overall, this approach revealed a wider bacterial (mainly gamma-Proteobacteria) and fungal diversity than previously found. Further, the use of a combination of different classification methods, in a software-independent way, helped to understand the actual composition of the microbial ecosystem under study. In addition, bacteriophage-related sequences were found. The bacterial diversity depended partially on the methods used, as composition-based methods predicted a wider diversity than sequence-based methods, and as classification methods based solely on phylogenetic marker genes predicted a more restricted diversity compared with methods that took all reads into account. The metagenomic sequencing analysis identified Hanseniaspora uvarum, Hanseniaspora opuntiae, Saccharomyces cerevisiae, Lactobacillus fermentum, and Acetobacter pasteurianus as the prevailing species. Also, the presence of occasional members of the cocoa bean fermentation process was revealed (such as Erwinia tasmaniensis, Lactobacillus brevis, Lactobacillus casei, Lactobacillus rhamnosus, Lactococcus lactis, Leuconostoc mesenteroides, and Oenococcus oeni). Furthermore, the sequence reads associated with viral communities were of a restricted diversity, dominated by Myoviridae and Siphoviridae, and reflecting Lactobacillus as the dominant host. To conclude, an accurate overview of all members of a cocoa bean fermentation process sample was revealed, indicating the superiority of metagenomic sequencing over previously used techniques. PMID- 22666443 TI - Differential effects of early- and late-life access to carotenoids on adult immune function and ornamentation in mallard ducks (Anas platyrhynchos). AB - Environmental conditions early in life can affect an organism's phenotype at adulthood, which may be tuned to perform optimally in conditions that mimic those experienced during development (Environmental Matching hypothesis), or may be generally superior when conditions during development were of higher quality (Silver Spoon hypothesis). Here, we tested these hypotheses by examining how diet during development interacted with diet during adulthood to affect adult sexually selected ornamentation and immune function in male mallard ducks (Anas platyrhynchos). Mallards have yellow, carotenoid-pigmented beaks that are used in mate choice, and the degree of beak coloration has been linked to adult immune function. Using a 2 * 2 factorial experimental design, we reared mallards on diets containing either low or high levels of carotenoids (nutrients that cannot be synthesized de novo) throughout the period of growth, and then provided adults with one of these two diets while simultaneously quantifying beak coloration and response to a variety of immune challenges. We found that both developmental and adult carotenoid supplementation increased circulating carotenoid levels during dietary treatment, but that birds that received low-carotenoid diets during development maintained relatively higher circulating carotenoid levels during an adult immune challenge. Individuals that received low levels of carotenoids during development had larger phytohemagglutinin (PHA)-induced cutaneous immune responses at adulthood; however, dietary treatment during development and adulthood did not affect antibody response to a novel antigen, nitric oxide production, natural antibody levels, hemolytic capacity of the plasma, or beak coloration. However, beak coloration prior to immune challenges positively predicted PHA response, and strong PHA responses were correlated with losses in carotenoid-pigmented coloration. In sum, we did not find consistent support for either the Environmental Matching or Silver Spoon hypotheses. We then describe a new hypothesis that should be tested in future studies examining developmental plasticity. PMID- 22666444 TI - Dynamics of multiple trafficking behaviors of individual synaptic vesicles revealed by quantum-dot based presynaptic probe. AB - Although quantum dots (QDs) have provided invaluable information regarding the diffusive behaviors of postsynaptic receptors, their application in presynaptic terminals has been rather limited. In addition, the diffraction-limited nature of the presynaptic bouton has hampered detailed analyses of the behaviors of synaptic vesicles (SVs) at synapses. Here, we created a quantum-dot based presynaptic probe and characterized the dynamic behaviors of individual SVs. As previously reported, the SVs exhibited multiple exchanges between neighboring boutons. Actin disruption induced a dramatic decrease in the diffusive behaviors of SVs at synapses while microtubule disruption only reduced extrasynaptic mobility. Glycine-induced synaptic potentiation produced significant increases in synaptic and inter-boutonal trafficking of SVs, which were NMDA receptor- and actin-dependent while NMDA-induced synaptic depression decreased the mobility of the SVs at synapses. Together, our results show that sPH-AP-QD revealed previously unobserved trafficking properties of SVs around synapses, and the dynamic modulation of SV mobility could regulate presynaptic efficacy during synaptic activity. PMID- 22666445 TI - Folic acid transport to the human fetus is decreased in pregnancies with chronic alcohol exposure. AB - BACKGROUND: During pregnancy, the demand for folic acid increases since the fetus requires this nutrient for its rapid growth and cell proliferation. The placenta concentrates folic acid into the fetal circulation; as a result the fetal levels are 2 to 4 times higher than the maternal level. Animal and in vitro studies have suggested that alcohol may impair transport of folic acid across the placenta by decreasing expression of transport proteins. We aim to determine if folate transfer to the fetus is altered in human pregnancies with chronic alcohol consumption. METHODOLOGY/PRINCIPAL FINDINGS: Serum folate was measured in maternal blood and umbilical cord blood at the time of delivery in pregnancies with chronic and heavy alcohol exposure (n = 23) and in non-drinking controls (n = 24). In the alcohol-exposed pairs, the fetal:maternal serum folate ratio was <= 1.0 in over half (n = 14), whereas all but one of the controls were >1.0. Mean folate in cord samples was lower in the alcohol-exposed group than in the controls (33.15 +/- 19.89 vs 45.91 +/- 20.73, p = 0.04). CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that chronic and heavy alcohol use in pregnancy impairs folate transport to the fetus. Altered folate concentrations within the placenta and in the fetus may in part contribute to the deficits observed in the fetal alcohol spectrum disorders. PMID- 22666446 TI - Mosquito, bird and human surveillance of West Nile and Usutu viruses in Emilia Romagna Region (Italy) in 2010. AB - BACKGROUND: In 2008, after the first West Nile virus (WNV) detection in the Emilia-Romagna region, a surveillance system, including mosquito- and bird-based surveillance, was established to evaluate the virus presence. Surveillance was improved in following years by extending the monitoring to larger areas and increasing the numbers of mosquitoes and birds tested. METHODOLOGY/PRINCIPAL FINDINGS: A network of mosquito traps, evenly distributed and regularly activated, was set up within the surveyed area. A total of 438,558 mosquitoes, grouped in 3,111 pools and 1,276 birds (1,130 actively sampled and 146 from passive surveillance), were tested by biomolecular analysis. The survey detected WNV in 3 Culex pipiens pools while Usutu virus (USUV) was found in 89 Cx. pipiens pools and in 2 Aedes albopictus pools. Two birds were WNV-positive and 12 were USUV-positive. Furthermore, 30 human cases of acute meningoencephalitis, possibly caused by WNV or USUV, were evaluated for both viruses and 1,053 blood bags were tested for WNV, without any positive result. CONCLUSIONS/SIGNIFICANCE: Despite not finding symptomatic human WNV infections during 2010, the persistence of the virus, probably due to overwintering, was confirmed through viral circulation in mosquitoes and birds, as well as for USUV. In 2010, circulation of the two viruses was lower and more delayed than in 2009, but this decrease was not explained by the relative abundance of Cx. pipiens mosquito, which was greater in 2010. The USUV detection in mosquito species confirms the role of Cx. pipiens as the main vector and the possible involvement of Ae. albopictus in the virus cycle. The effects of meteorological conditions on the presence of USUV-positive mosquito pools were considered finding an association with drought conditions and a wide temperature range. The output produced by the surveillance system demonstrated its usefulness and reliability in terms of planning public health policies. PMID- 22666447 TI - A DNA barcode library for North American Ephemeroptera: progress and prospects. AB - DNA barcoding of aquatic macroinvertebrates holds much promise as a tool for taxonomic research and for providing the reliable identifications needed for water quality assessment programs. A prerequisite for identification using barcodes is a reliable reference library. We gathered 4165 sequences from the barcode region of the mitochondrial cytochrome c oxidase subunit I gene representing 264 nominal and 90 provisional species of mayflies (Insecta: Ephemeroptera) from Canada, Mexico, and the United States. No species shared barcode sequences and all can be identified with barcodes with the possible exception of some Caenis. Minimum interspecific distances ranged from 0.3-24.7% (mean: 12.5%), while the average intraspecific divergence was 1.97%. The latter value was inflated by the presence of very high divergences in some taxa. In fact, nearly 20% of the species included two or three haplotype clusters showing greater than 5.0% sequence divergence and some values are as high as 26.7%. Many of the species with high divergences are polyphyletic and likely represent species complexes. Indeed, many of these polyphyletic species have numerous synonyms and individuals in some barcode clusters show morphological attributes characteristic of the synonymized species. In light of our findings, it is imperative that type or topotype specimens be sequenced to correctly associate barcode clusters with morphological species concepts and to determine the status of currently synonymized species. PMID- 22666448 TI - Targeting antibody responses to the membrane proximal external region of the envelope glycoprotein of human immunodeficiency virus. AB - Although human immunodeficiency type 1 (HIV-1) infection induces strong antibody responses to the viral envelope glycoprotein (Env) only a few of these antibodies possess the capacity to neutralize a broad range of strains. The induction of such antibodies represents an important goal in the development of a preventive vaccine against the infection. Among the broadly neutralizing monoclonal antibodies discovered so far, three (2F5, Z13 and 4E10) target the short and hidden membrane proximal external region (MPER) of the gp41 transmembrane protein. Antibody responses to MPER are rarely observed in HIV-infected individuals or after immunization with Env immunogens. To initiate antibody responses to MPER in its membrane-embedded native conformation, we generated expression plasmids encoding the membrane-anchored ectodomain of gp41 with N terminal deletions of various sizes. Following transfection of these plasmids, the MPER domains are displayed on the cell surface and incorporated into HIV virus like particles (VLP). Transfected cells displaying MPER mutants bound as efficiently to both 2F5 and 4E10 as cells transfected with a plasmid encoding full-length Env. Mice immunized with VLPs containing the MPER mutants produced MPER-specific antibodies, the levels of which could be increased by the trimerization of the displayed proteins as well as by a DNA prime-VLP boost immunization strategy. Although 2F5 competed for binding to MPER with antibodies in sera of some of the immunized mice, neutralizing activity could not be detected. Whether this is due to inefficient binding of the induced antibodies to MPER in the context of wild type Env or whether the overall MPER-specific antibody response induced by the MPER display mutants is too low to reveal neutralizing activity, remains to be determined. PMID- 22666449 TI - A cost-effective transparency-based digital imaging for efficient and accurate wound area measurement. AB - Wound measurement is an objective and direct way to trace the course of wound healing and to evaluate therapeutic efficacy. Nevertheless, the accuracy and efficiency of the current measurement methods need to be improved. Taking the advantages of reliability of transparency tracing and the accuracy of computer aided digital imaging, a transparency-based digital imaging approach is established, by which data from 340 wound tracing were collected from 6 experimental groups (8 rats/group) at 8 experimental time points (Day 1, 3, 5, 7, 10, 12, 14 and 16) and orderly archived onto a transparency model sheet. This sheet was scanned and its image was saved in JPG form. Since a set of standard area units from 1 mm(2) to 1 cm(2) was integrated into the sheet, the tracing areas in JPG image were measured directly, using the "Magnetic lasso tool" in Adobe Photoshop program. The pixel values/PVs of individual outlined regions were obtained and recorded in an average speed of 27 second/region. All PV data were saved in an excel form and their corresponding areas were calculated simultaneously by the formula of Y (PV of the outlined region)/X (PV of standard area unit) * Z (area of standard unit). It took a researcher less than 3 hours to finish area calculation of 340 regions. In contrast, over 3 hours were expended by three skillful researchers to accomplish the above work with traditional transparency-based method. Moreover, unlike the results obtained traditionally, little variation was found among the data calculated by different persons and the standard area units in different sizes and shapes. Given its accurate, reproductive and efficient properties, this transparency-based digital imaging approach would be of significant values in basic wound healing research and clinical practice. PMID- 22666450 TI - Organic farming and landscape structure: effects on insect-pollinated plant diversity in intensively managed grasslands. AB - Parallel declines in insect-pollinated plants and their pollinators have been reported as a result of agricultural intensification. Intensive arable plant communities have previously been shown to contain higher proportions of self pollinated plants compared to natural or semi-natural plant communities. Though intensive grasslands are widespread, it is not known whether they show similar patterns to arable systems nor whether local and/or landscape factors are influential. We investigated plant community composition in 10 pairs of organic and conventional dairy farms across Ireland in relation to the local and landscape context. Relationships between plant groups and local factors (farming system, position in field and soil parameters) and landscape factors (e.g. landscape complexity) were investigated. The percentage cover of unimproved grassland was used as an inverse predictor of landscape complexity, as it was negatively correlated with habitat-type diversity. Intensive grasslands (organic and conventional) contained more insect-pollinated forbs than non-insect pollinated forbs. Organic field centres contained more insect-pollinated forbs than conventional field centres. Insect-pollinated forb richness in field edges (but not field centres) increased with increasing landscape complexity (% unimproved grassland) within 1, 3, 4 and 5km radii around sites, whereas non insect pollinated forb richness was unrelated to landscape complexity. Pollination systems within intensive grassland communities may be different from those in arable systems. Our results indicate that organic management increases plant richness in field centres, but that landscape complexity exerts strong influences in both organic and conventional field edges. Insect-pollinated forb richness, unlike that for non-insect pollinated forbs, showed positive relationships to landscape complexity reflecting what has been documented for bees and other pollinators. The insect-pollinated forbs, their pollinators and landscape context are clearly linked. This needs to be taken into account when managing and conserving insect-pollinated plant and pollinator communities. PMID- 22666451 TI - Down-regulation of neogenin accelerated glioma progression through promoter Methylation and its overexpression in SHG-44 Induced Apoptosis. AB - BACKGROUND: Dependence receptors have been proved to act as tumor suppressors in tumorigenesis. Neogenin, a DCC homologue, well known for its fundamental role in axon guidance and cellular differentiation, is also a dependence receptor functioning to control apoptosis. However, loss of neogenin has been reported in several kinds of cancers, but its role in glioma remains to be further investigated. METHODOLOGY/PRINCIPAL FINDINGS: Western blot analysis showed that neogenin level was lower in glioma tissues than in their matching surrounding non neoplastic tissues (n = 13, p<0.01). By immunohistochemical analysis of 69 primary and 16 paired initial and recurrent glioma sections, we found that the loss of neogenin did not only correlate negatively with glioma malignancy (n = 69, p<0.01), but also glioma recurrence (n = 16, p<0.05). Kaplan-Meier plot and Cox proportional hazards modelling showed that over-expressive neogenin could prolong the tumor latency (n = 69, p<0.001, 1187.6 +/- 162.6 days versus 687.4 +/ 254.2 days) and restrain high-grade glioma development (n = 69, p<0.01, HR: 0.264, 95% CI: 0.102 to 0.687). By Methylation specific polymerase chain reaction (MSP), we reported that neogenin promoter was methylated in 31.0% (9/29) gliomas, but absent in 3 kinds of glioma cell lines. Interestingly, the prevalence of methylation in high-grade gliomas was higher than low-grade gliomas and non neoplastic brain tissues (n = 33, p<0.05) and overall methylation rate increased as glioma malignancy advanced. Furthermore, when cells were over-expressed by neogenin, the apoptotic rate in SHG-44 was increased to 39.7% compared with 8.1% in the blank control (p<0.01) and 9.3% in the negative control (p<0.01). CONCLUSIONS/SIGNIFICANCE: These observations recapitulated the proposed role of neogenin as a tumor suppressor in gliomas and we suggest its down-regulation owing to promoter methylation is a selective advantage for glioma genesis, progression and recurrence. Furthermore, the induction of apoptosis in SHG-44 cells after overexpression of neogenin, indicated that neogenin could be a novel target for glioma therapy. PMID- 22666452 TI - Phage-induced expression of CRISPR-associated proteins is revealed by shotgun proteomics in Streptococcus thermophilus. AB - The CRISPR/Cas system, comprised of clustered regularly interspaced short palindromic repeats along with their associated (Cas) proteins, protects bacteria and archaea from viral predation and invading nucleic acids. While the mechanism of action for this acquired immunity is currently under investigation, the response of Cas protein expression to phage infection has yet to be elucidated. In this study, we employed shotgun proteomics to measure the global proteome expression in a model system for studying the CRISPR/Cas response in S. thermophilus DGCC7710 infected with phage 2972. Host and viral proteins were simultaneously measured following inoculation at two different multiplicities of infection and across various time points using two-dimensional liquid chromatography tandem mass spectrometry. Thirty-seven out of forty predicted viral proteins were detected, including all proteins of the structural virome and viral effector proteins. In total, 1,013 of 2,079 predicted S. thermophilus proteins were detected, facilitating the monitoring of host protein synthesis changes in response to virus infection. Importantly, Cas proteins from all four CRISPR loci in the S. thermophilus DGCC7710 genome were detected, including loci previously thought to be inactive. Many Cas proteins were found to be constitutively expressed, but several demonstrated increased abundance following infection, including the signature Cas9 proteins from the CRISPR1 and CRISPR3 loci, which are key players in the interference phase of the CRISPR/Cas response. Altogether, these results provide novel insights into the proteomic response of S. thermophilus, specifically CRISPR-associated proteins, upon phage 2972 infection. PMID- 22666453 TI - Discriminating active from latent tuberculosis in patients presenting to community clinics. AB - BACKGROUND: Because of the high global prevalence of latent TB infection (LTBI), a key challenge in endemic settings is distinguishing patients with active TB from patients with overlapping clinical symptoms without active TB but with co existing LTBI. Current methods are insufficiently accurate. Plasma proteomic fingerprinting can resolve this difficulty by providing a molecular snapshot defining disease state that can be used to develop point-of-care diagnostics. METHODS: Plasma and clinical data were obtained prospectively from patients attending community TB clinics in Peru and from household contacts. Plasma was subjected to high-throughput proteomic profiling by mass spectrometry. Statistical pattern recognition methods were used to define mass spectral patterns that distinguished patients with active TB from symptomatic controls with or without LTBI. RESULTS: 156 patients with active TB and 110 symptomatic controls (patients with respiratory symptoms without active TB) were investigated. Active TB patients were distinguishable from undifferentiated symptomatic controls with accuracy of 87% (sensitivity 84%, specificity 90%), from symptomatic controls with LTBI (accuracy of 87%, sensitivity 89%, specificity 82%) and from symptomatic controls without LTBI (accuracy 90%, sensitivity 90%, specificity 92%). CONCLUSIONS: We show that active TB can be distinguished accurately from LTBI in symptomatic clinic attenders using a plasma proteomic fingerprint. Translation of biomarkers derived from this study into a robust and affordable point-of-care format will have significant implications for recognition and control of active TB in high prevalence settings. PMID- 22666454 TI - Functional dissociation of ongoing oscillatory brain states. AB - The state of a neural assembly preceding an incoming stimulus is assumed to modulate the processing of subsequently presented stimuli. The nature of this state can differ with respect to the frequency of ongoing oscillatory activity. Oscillatory brain activity of specific frequency range such as alpha (8-12 Hz) and gamma (above 30 Hz) band oscillations are hypothesized to play a functional role in cognitive processing. Therefore, a selective modulation of this prestimulus activity could clarify the functional role of these prestimulus fluctuations. For this purpose, we adopted a novel non-invasive brain-computer interface (BCI) strategy to selectively increase alpha or gamma band activity in the occipital cortex combined with an adaptive presentation of visual stimuli within specific brain states. During training, oscillatory brain activity was estimated online and fed back to the participants to enable a deliberate modulation of alpha or gamma band oscillations. Results revealed that volunteers selectively increased alpha and gamma frequency oscillations with a high level of specificity regarding frequency range and localization. At testing, alpha or gamma band activity was classified online and at defined levels of activity, visual objects embedded in noise were presented instantly and had to be detected by the volunteer. In experiment I, the effect of two levels of prestimulus gamma band activity on visual processing was examined. During phases of increased gamma band activity significantly more visual objects were detected. In experiment II, the effect was compared against increased levels of alpha band activity. An improvement of visual processing was only observed for enhanced gamma band activity. Both experiments demonstrate the specific functional role of prestimulus gamma band oscillations for perceptual processing. We propose that the BCI method permits the selective modulation of oscillatory activity and the direct assessment of behavioral consequences to test for functional dissociations of different oscillatory brain states. PMID- 22666455 TI - High-throughput sequencing of 16S rRNA gene amplicons: effects of extraction procedure, primer length and annealing temperature. AB - The analysis of 16S-rDNA sequences to assess the bacterial community composition of a sample is a widely used technique that has increased with the advent of high throughput sequencing. Although considerable effort has been devoted to identifying the most informative region of the 16S gene and the optimal informatics procedures to process the data, little attention has been paid to the PCR step, in particular annealing temperature and primer length. To address this, amplicons derived from 16S-rDNA were generated from chicken caecal content DNA using different annealing temperatures, primers and different DNA extraction procedures. The amplicons were pyrosequenced to determine the optimal protocols for capture of maximum bacterial diversity from a chicken caecal sample. Even at very low annealing temperatures there was little effect on the community structure, although the abundance of some OTUs such as Bifidobacterium increased. Using shorter primers did not reveal any novel OTUs but did change the community profile obtained. Mechanical disruption of the sample by bead beating had a significant effect on the results obtained, as did repeated freezing and thawing. In conclusion, existing primers and standard annealing temperatures captured as much diversity as lower annealing temperatures and shorter primers. PMID- 22666456 TI - In vitro and in vivo anti-angiogenic activities of Panduratin A. AB - BACKGROUND: Targeting angiogenesis has emerged as an attractive and promising strategy in anti-cancer therapeutic development. The present study investigates the anti-angiogenic potential of Panduratin A (PA), a natural chalcone isolated from Boesenbergia rotunda by using both in vitro and in vivo assays. METHODOLOGY/PRINCIPAL FINDINGS: PA exerted selective cytotoxicity on human umbilical vein endothelial cells (HUVECs) with IC(50) value of 6.91 +/- 0.85 uM when compared to human normal fibroblast and normal liver epithelial cells. Assessment of the growth kinetics by cell impedance-based Real-Time Cell Analyzer showed that PA induced both cytotoxic and cytostatic effects on HUVECs, depending on the concentration used. Results also showed that PA suppressed VEGF-induced survival and proliferation of HUVECs. Furthermore, endothelial cell migration, invasion, and morphogenesis or tube formation demonstrated significant time- and dose-dependent inhibition by PA. PA also suppressed matrix metalloproteinase-2 (MMP-2) secretion and attenuated its activation to intermediate and active MMP-2. In addition, PA suppressed F-actin stress fiber formation to prevent migration of the endothelial cells. More importantly, anti-angiogenic potential of PA was also evidenced in two in vivo models. PA inhibited neo-vessels formation in murine Matrigel plugs, and angiogenesis in zebrafish embryos. CONCLUSIONS/SIGNIFICANCE: Taken together, our study demonstrated the distinctive anti-angiogenic properties of PA, both in vitro and in vivo. This report thus reveals another biological activity of PA in addition to its reported anti-inflammatory and anti-cancer activities, suggestive of PA's potential for development as an anti-angiogenic agent for cancer therapy. PMID- 22666457 TI - The smell of age: perception and discrimination of body odors of different ages. AB - Our natural body odor goes through several stages of age-dependent changes in chemical composition as we grow older. Similar changes have been reported for several animal species and are thought to facilitate age discrimination of an individual based on body odors, alone. We sought to determine whether humans are able to discriminate between body odor of humans of different ages. Body odors were sampled from three distinct age groups: Young (20-30 years old), Middle-age (45-55), and Old-age (75-95) individuals. Perceptual ratings and age discrimination performance were assessed in 41 young participants. There were significant differences in ratings of both intensity and pleasantness, where body odors from the Old-age group were rated as less intense and less unpleasant than body odors originating from Young and Middle-age donors. Participants were able to discriminate between age categories, with body odor from Old-age donors mediating the effect also after removing variance explained by intensity differences. Similarly, participants were able to correctly assign age labels to body odors originating from Old-age donors but not to body odors originating from other age groups. This experiment suggests that, akin to other animals, humans are able to discriminate age based on body odor alone and that this effect is mediated mainly by body odors emitted by individuals of old age. PMID- 22666458 TI - An in situ autologous tumor vaccination with combined radiation therapy and TLR9 agonist therapy. AB - PURPOSE: Recent studies have shown that a new generation of synthetic agonist of Toll-like receptor (TLR) 9 consisting a 3'-3'-attached structure and a dCp7-deaza dG dinucultodie shows more potent immunostimulatory effects in both mouse and human than conventional CpG oligonucleotides. Radiation therapy (RT) provides a source of tumor antigens that are released from dying, irradiated, tumor cells without causing systemic immunosuppression. We, therefore, examined effect of combining RT with a designer synthetic agonist of TLR9 on anti-tumoral immunity, primary tumor growth retardation and metastases in a murine model of lung cancer. METHODS: Grouped C57BL/6 and congenic B cell deficient mice (B(-/-)) bearing footpad 3LL tumors were treated with PBS, TLR9 agonist, control oligonucelotide, RT or the combination of RT and TLR9 agonist. Immune phenotype of splenocytes and serum IFN-gamma and IL-10 levels were analyzed by FACS and ELISA, 24 h after treatment. Tumor growth, lung metastases and survival rate were monitored and tumor specific antibodies in serum and deposition in tumor tissue were measured by ELISA and immunofluorescence. RESULTS: TLR9 agonist expanded and activated B cells and plasmacytoid dendritic cells in wild-type mice and natural killer DCs (NKDCs) in B cell-deficient (B(-/-)) mice bearing ectopic Lewis lung adenocarcinoma (3LL). Combined RT with TLR9 agonist treatment inhibited 3LL tumor growth in both wild type and B(-/-) mice. A strong tumor-specific humoral immune response (titer: 1/3200) with deposition of mouse IgG auto-antibodies in tumor tissue were found in wildtype mice, whereas the number of tumor infiltrating NKDCs increased in B(-/-) mice following RT+ TLR9 agonist therapy. Furthermore, mice receiving combination therapy had fewer lung metastases and a higher survival than single treatment cohorts. CONCLUSIONS: Combination therapy with TLR9 agonist and RT induces systemic anti-tumoral humoral response, augments tumoral infiltration of NKDCs, reduces pulmonary metastases and improves survival in a murine model of 3LL cancer. PMID- 22666459 TI - Comparing the invasibility of experimental "reefs" with field observations of natural reefs and artificial structures. AB - Natural systems are increasingly being modified by the addition of artificial habitats which may facilitate invasion. Where invaders are able to disperse from artificial habitats, their impact may spread to surrounding natural communities and therefore it is important to investigate potential factors that reduce or enhance invasibility. We surveyed the distribution of non-indigenous and native invertebrates and algae between artificial habitats and natural reefs in a marine subtidal system. We also deployed sandstone plates as experimental 'reefs' and manipulated the orientation, starting assemblage and degree of shading. Invertebrates (non-indigenous and native) appeared to be responding to similar environmental factors (e.g. orientation) and occupied most space on artificial structures and to a lesser extent reef walls. Non-indigenous invertebrates are less successful than native invertebrates on horizontal reefs despite functional similarities. Manipulative experiments revealed that even when non-indigenous invertebrates invade vertical "reefs", they are unlikely to gain a foothold and never exceed covers of native invertebrates (regardless of space availability). Community ecology suggests that invertebrates will dominate reef walls and algae horizontal reefs due to functional differences, however our surveys revealed that native algae dominate both vertical and horizontal reefs in shallow estuarine systems. Few non-indigenous algae were sampled in the study, however where invasive algal species are present in a system, they may present a threat to reef communities. Our findings suggest that non-indigenous species are less successful at occupying space on reef compared to artificial structures, and manipulations of biotic and abiotic conditions (primarily orientation and to a lesser extent biotic resistance) on experimental "reefs" explained a large portion of this variation, however they could not fully explain the magnitude of differences. PMID- 22666460 TI - ANKRD26 and its interacting partners TRIO, GPS2, HMMR and DIPA regulate adipogenesis in 3T3-L1 cells. AB - Partial inactivation of the Ankyrin repeat domain 26 (Ankrd26) gene causes obesity and diabetes in mice and increases spontaneous and induced adipogenesis in mouse embryonic fibroblasts. However, it is not yet known how the Ankrd26 protein carries out its biological functions. We identified by yeast two-hybrid and immunoprecipitation assays the triple functional domain protein (TRIO), the G protein pathway suppressor 2 (GPS2), the delta-interacting protein A (DIPA) and the hyaluronan-mediated motility receptor (HMMR) as ANKRD26 interacting partners. Adipogenesis of 3T3-L1 cells was increased by selective down-regulation of Ankrd26, Trio, Gps2, Hmmr and Dipa. Furthermore, GPS2 and DIPA, which are normally located in the nucleus, were translocated to the cytoplasm, when the C terminus of ANKRD26 was introduced into these cells. These findings provide biochemical evidence that ANKRD26, TRIO, GPS2 and HMMR are novel and important regulators of adipogenesis and identify new targets for the modulation of adipogenesis. PMID- 22666461 TI - Variance and autocorrelation of the spontaneous slow brain activity. AB - Slow (<0.1 Hz) oscillatory activity in the human brain, as measured by functional magnetic imaging, has been used to identify neural networks and their dysfunction in specific brain diseases. Its intrinsic properties may also be useful to investigate brain functions. We investigated the two functional maps: variance and first order autocorrelation coefficient (r(1)). These two maps had distinct spatial distributions and the values were significantly different among the subdivisions of the precuneus and posterior cingulate cortex that were identified in functional connectivity (FC) studies. The results reinforce the functional segregation of these subdivisions and indicate that the intrinsic properties of the slow brain activity have physiological relevance. Further, we propose a sample size (degree of freedom) correction when assessing the statistical significance of FC strength with r(1) values, which enables a better understanding of the network changes related to various brain diseases. PMID- 22666462 TI - Phylogeographic analysis elucidates the influence of the ice ages on the disjunct distribution of relict dragonflies in Asia. AB - Unusual biogeographic patterns of closely related groups reflect events in the past, and molecular analyses can help to elucidate these events. While ample research on the origin of disjunct distributions of different organism groups in the Western Paleartic has been conducted, such studies are rare for Eastern Palearctic organisms. In this paper we present a phylogeographic analysis of the disjunct distribution pattern of the extant species of the strongly cool-adapted Epiophlebia dragonflies from Asia. We investigated sequences of the usually more conserved 18 S rDNA and 28 S rDNA genes and the more variable sequences of ITS1, ITS2 and CO2 of all three currently recognised Epiophlebia species and of a sample of other odonatan species. In all genes investigated the degrees of similarity between species of Epiophlebia are very high and resemble those otherwise found between different populations of the same species in Odonata. This indicates that substantial gene transfer between these populations occurred in the comparatively recent past. Our analyses imply a wide distribution of the ancestor of extant Epiophlebia in Southeast Asia during the last ice age, when suitable habitats were more common. During the following warming phase, its range contracted, resulting in the current disjunct distribution. Given the strong sensitivity of these species to climatic parameters, the current trend to increasing global temperatures will further reduce acceptable habitats and seriously threaten the existences of these last representatives of an ancient group of Odonata. PMID- 22666463 TI - Role of operon aaoSo-mutT in antioxidant defense in Streptococcus oligofermentans. AB - Previously, we have found that an insertional inactivation of aao(So), a gene encoding L-amino acid oxidase (LAAO), causes marked repression of the growth of Streptococcus oligofermentans. Here, we found that aao(So) and mutT, a homolog of pyrophosphohydrolase gene of Escherichia coli, constituted an operon. Deletion of either gene did not impair the growth of S. oligofermentans, but double deletion of both aao(So) and mutT was lethal. Quantitative PCR showed that the transcript abundance of mutT was reduced for 13-fold in the aao(So) insertional mutant, indicating that gene polarity derived from the inactivation of aao(So) attenuated the expression of mutT. Enzymatic assays were conducted to determine the biochemical functions of LAAO and MutT of S. oligofermentans. The results indicated that LAAO functioned as an aminoacetone oxidase [47.75 nmol H(2)O(2) (min . mg protein)(-1)]; and MutT showed the pyrophosphohydrolase activity, which removed mutagens such as 8-oxo-dGTP. Like paraquat, aao(So) mutations increased the expression of SOD, and addition of aminoacetone (final concentration, 5 mM) decreased the mutant's growth by 11%, indicating that the aao(So) mutants are under ROS stress. HPLC did reveal elevated levels of cytoplasmic aminoacetone in both the deletion and insertional gene mutants of aao(So). Electron spin resonance spectroscopy showed increased hydroxyl radicals in both types of aao(So) mutant. This demonstrated that inactivation of aao(So) caused the elevation of the prooxidant aminoacetone, resulting the cellular ROS stress. Our study indicates that the presence of both LAAO and MutT can prevent endogenous metabolites-generated ROS and mutagens. In this way, we were able to determine the role of the aao(So)-mutT operon in antioxidant defense in S. oligofermentans. PMID- 22666464 TI - Regional dissemination of a trimethoprim-resistance gene cassette via a successful transposable element. AB - BACKGROUND: Antimicrobial resistance is a growing international problem. We observed a 50% increase in the prevalence of trimethoprim resistance among fecal Escherichia coli from healthy Nigerian students between 1998 and 2005, a trend to increase that continued in 2009. METHODS AND FINDINGS: A PCR-based screen revealed that 131 (43.1%) of isolates obtained in Nigeria in 2005 and 2009 carried integron-borne dfrA cassettes. In the case of 67 (51.1%) of these isolates, the cassette was a class 1-integron-borne dfrA7 gene, which has been reported at high prevalence from E. coli isolates from other parts of Africa. Complete sequencing of a 27 Kb dfrA7-bearing plasmid from one isolate located the dfrA7 gene within a Tn21-type transposon. The transposon also contained an IS26 derived bla/sul/str element, encoding resistance to beta-lactams, sulphonamides and streptomycin, and mercury resistance genes. Although the plasmid backbone was only found in 12 (5.8%) of trimethoprim-resistant isolates, dfrA7 and other transposon-borne genes were detected in 14 (16.3%) and 32 (26.3%) of trimethoprim resistant isolates collected in Nigeria in 2005 and 2009, respectively. Additionally, 37 (19.3%) of trimethoprim-resistant E. coli isolates collected between 2006 and 2008 from Ghana were positive for the dfrA7 and a transposon marker, but only 4 (2.1%) harbored the plasmid backbone. CONCLUSIONS: Our data point to transposition as a principal mechanism for disseminating dfrA7 among E. coli from Nigeria and Ghana. On-going intensive use of the affordable broad spectrum antibacterials is likely to promote selective success of a highly prevalent transposable element in West Africa. PMID- 22666465 TI - Transcriptional activation of low-density lipoprotein receptor gene by DJ-1 and effect of DJ-1 on cholesterol homeostasis. AB - DJ-1 is a novel oncogene and also causative gene for familial Parkinson's disease park7. DJ-1 has multiple functions that include transcriptional regulation, anti oxidative reaction and chaperone and mitochondrial regulation. For transcriptional regulation, DJ-1 acts as a coactivator that binds to various transcription factors, resulting in stimulation or repression of the expression of their target genes. In this study, we found the low-density lipoprotein receptor (LDLR) gene is a transcriptional target gene for DJ-1. Reduced expression of LDLR mRNA and protein was observed in DJ-1-knockdown cells and DJ-1 knockout mice and this occurred at the transcription level. Reporter gene assays using various deletion and point mutations of the LDLR promoter showed that DJ-1 stimulated promoter activity by binding to the sterol regulatory element (SRE) with sterol regulatory element binding protein (SREBP) and that stimulating activity of DJ-1 toward LDLR promoter activity was enhanced by oxidation of DJ-1. Chromatin immunoprecipitation, gel-mobility shift and co-immunoprecipitation assays showed that DJ-1 made a complex with SREBP on the SRE. Furthermore, it was found that serum LDL cholesterol level was increased in DJ-1-knockout male, but not female, mice and that the increased serum LDL cholesterol level in DJ-1 knockout male mice was cancelled by administration with estrogen, suggesting that estrogen compensates the increased level of serum LDL cholesterol in DJ-1 knockout female mice. This is the first report that DJ-1 participates in metabolism of fatty acid synthesis through transcriptional regulation of the LDLR gene. PMID- 22666466 TI - The transcriptional regulator CzcR modulates antibiotic resistance and quorum sensing in Pseudomonas aeruginosa. AB - The opportunistic pathogen Pseudomonas aeruginosa responds to zinc, cadmium and cobalt by way of the CzcRS two-component system. In presence of these metals the regulatory protein CzcR induces the expression of the CzcCBA efflux pump, expelling and thereby inducing resistance to Zn, Cd and Co. Importantly, CzcR co regulates carbapenem antibiotic resistance by repressing the expression of the OprD porin, the route of entry for these antibiotics. This unexpected co regulation led us to address the role of CzcR in other cellular processes unrelated to the metal response. We found that CzcR affected the expression of numerous genes directly involved in the virulence of P. aeruginosa even in the absence of the inducible metals. Notably the full expression of quorum sensing 3 oxo-C12-HSL and C4-HSL autoinducer molecules is impaired in the absence of CzcR. In agreement with this, the virulence of the czcRS deletion mutant is affected in a C. elegans animal killing assay. Additionally, chromosome immunoprecipitation experiments allowed us to localize CzcR on the promoter of several regulated genes, suggesting a direct control of target genes such as oprD, phzA1 and lasI. All together our data identify CzcR as a novel regulator involved in the control of several key genes for P. aeruginosa virulence processes. PMID- 22666468 TI - Low immune response to hepatitis B vaccine among children in Dakar, Senegal. AB - HBV vaccine was introduced into the Expanded Programme on Immunization (EPI) in Senegal and Cameroon in 2005. We conducted a cross-sectional study in both countries to assess the HBV immune protection among children. All consecutive children under 4 years old, hospitalized for any reason between May 2009 and May 2010, with an immunisation card and a complete HBV vaccination, were tested for anti-HBs and anti-HBc. A total of 242 anti-HBc-negative children (128 in Cameroon and 114 in Senegal) were considered in the analysis. The prevalence of children with anti-HBs >= 10 IU/L was higher in Cameroon with 92% (95% CI: 87%-97%) compared to Senegal with 58% (95% CI: 49%-67%), (p<0.001). The response to vaccination in Senegal was lower in 2006-2007 (43%) than in 2008-2009 (65%), (p = 0.028). Our results, although not based on a representative sample of Senegalese or Cameroonian child populations, reveal a significant problem in vaccine response in Senegal. This response problem extends well beyond hepatitis B: the same children who have not developed an immune response to the HBV vaccine are also at risk for diphtheria, tetanus, pertussis (DTwP) and Haemophilus influenzae type b (Hib). Field biological monitoring should be carried out regularly in resource-poor countries to check quality of the vaccine administered. PMID- 22666467 TI - Exploring the midgut transcriptome and brush border membrane vesicle proteome of the rice stem borer, Chilo suppressalis (Walker). AB - The rice stem borer, Chilo suppressalis (Walker) (Lepidoptera: Pyralidae), is one of the most detrimental pests affecting rice crops. The use of Bacillus thuringiensis (Bt) toxins has been explored as a means to control this pest, but the potential for C. suppressalis to develop resistance to Bt toxins makes this approach problematic. Few C. suppressalis gene sequences are known, which makes in-depth study of gene function difficult. Herein, we sequenced the midgut transcriptome of the rice stem borer. In total, 37,040 contigs were obtained, with a mean size of 497 bp. As expected, the transcripts of C. suppressalis shared high similarity with arthropod genes. Gene ontology and KEGG analysis were used to classify the gene functions in C. suppressalis. Using the midgut transcriptome data, we conducted a proteome analysis to identify proteins expressed abundantly in the brush border membrane vesicles (BBMV). Of the 100 top abundant proteins that were excised and subjected to mass spectrometry analysis, 74 share high similarity with known proteins. Among these proteins, Western blot analysis showed that Aminopeptidase N and EH domain-containing protein have the binding activities with Bt-toxin Cry1Ac. These data provide invaluable information about the gene sequences of C. suppressalis and the proteins that bind with Cry1Ac. PMID- 22666469 TI - Noninvasive prenatal diagnosis of fetal trisomy 21 by allelic ratio analysis using targeted massively parallel sequencing of maternal plasma DNA. AB - BACKGROUND: Plasma DNA obtained from a pregnant woman contains a mixture of maternal and fetal DNA. The fetal DNA proportion in maternal plasma is relatively consistent as determined using polymorphic genetic markers across different chromosomes in euploid pregnancies. For aneuploid pregnancies, the observed fetal DNA proportion measured using polymorphic genetic markers for the aneuploid chromosome would be perturbed. In this study, we investigated the feasibility of analyzing single nucleotide polymorphisms using targeted massively parallel sequencing to detect such perturbations in mothers carrying trisomy 21 fetuses. METHODOLOGY/PRINCIPAL FINDINGS: DNA was extracted from plasma samples collected from fourteen pregnant women carrying singleton fetuses. Hybridization-based targeted sequencing was used to enrich 2 906 single nucleotide polymorphism loci on chr7, chr13, chr18 and chr21. Plasma DNA libraries with and without target enrichment were analyzed by massively parallel sequencing. Genomic DNA samples of both the mother and fetus for each case were genotyped by single nucleotide polymorphism microarray analysis. For the targeted regions, the mean sequencing depth of the enriched samples was 225-fold higher than that of the non-enriched samples. From the targeted sequencing data, the ratio between fetus-specific and shared alleles increased by approximately 2-fold on chr21 in the paternally derived trisomy 21 case. In comparison, the ratio is decreased by approximately 11% on chr21 in the maternally-derived trisomy 21 cases but with much overlap with the ratio of the euploid cases. Computer simulation revealed the relationship between the fetal DNA proportion, the number of informative alleles and the depth of sequencing. CONCLUSIONS/SIGNIFICANCE: Targeted massively parallel sequencing of single nucleotide polymorphism loci in maternal plasma DNA is a potential approach for trisomy 21 detection. However, the method appears to be less robust than approaches using non-polymorphism-based counting of sequence tags in plasma. PMID- 22666470 TI - Brain circuitries involved in semantic interference by demands of emotional and non-emotional distractors. AB - BACKGROUND: Previous studies have indicated that the processes leading to the resolution of emotional and non-emotional interference conflicts are unrelated, involving separate networks. It is also known that conflict resolution itself suggests a considerable overlap of the networks. Our study is an attempt to examine how these findings may be related. METHODOLOGY/PRINCIPAL FINDINGS: We used functional magnetic resonance imaging (fMRI) to study neural responses of 24 healthy subjects to emotional and non-emotional conflict paradigms involving the presentation of congruent and incongruent word-face pairs based on semantic incompatibility between targets and distractors. In the emotional task, the behavioral interference conflict was greater (compared to the non-emotional task) and was paralleled by involvement of the extrastriate visual and posterodorsal medial frontal cortices. In both tasks, we also observed a common network including the dorsal anterior cingulate, the supplemental motor area, the anterior insula and the inferior prefrontal cortex, indicating that these brain structures are markers of experienced conflict. However, the emotional task involved conflict-triggered networks to a considerably higher degree. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that responses to emotional and non-emotional distractors involve the same systems, which are capable of flexible adjustments based on conflict demands. The function of systems related to conflict resolution is likely to be adjusted on the basis of an evaluation process that primarily involves the extrastriate visual cortex, with target playing a significant role. PMID- 22666471 TI - Attenuated EAN in TNF-alpha deficient mice is associated with an altered balance of M1/M2 macrophages. AB - The role of tumor necrosis factor (TNF)-alpha and its receptors in neuroautoimmune and neuroinflammatory diseases has been controversial. On the basis of our previous studies, we hereby aimed to further clarify TNF-alpha's mechanism of action and to explore the potential role of TNF-alpha receptor (TNFR)1 as a therapeutic target in experimental autoimmune neuritis (EAN). EAN was induced by immunization with P0 peptide 180-199 in TNF-alpha knockout (KO) mice and anti-TNFR1 antibodies were used to treat EAN. Particularly, the effects of TNF-alpha deficiency and TNFR1 blockade on macrophage functions were investigated. The onset of EAN in TNF-alpha KO mice was markedly later than that in wild type (WT) mice. From day 14 post immunization, the clinical signs of TNF alpha KO mice were significantly milder than those of their WT counterparts. Further, we showed that the clinical severity of WT mice treated with anti-TNFR1 antibodies was less severe than that of the control WT mice receiving PBS. Nevertheless, no difference with regard to the clinical signs of EAN or inflammatory infiltration in cauda equina was seen between TNF-alpha KO and WT mice with EAN after blockade of TNFR1. Although TNF-alpha deficiency did not alter the proliferation of lymphocytes in response to either antigenic or mitogenic stimuli, it down-regulated the production of interleukin (IL)-12 and nitric oxide (NO), and enhanced the production of IL-10 in macrophages. Increased ratio of regulatory T cells (Tregs) and reduced production of interferon (IFN) gamma in cauda equina infiltrating cells, and elevated levels of IgG2b antibodies against P0 peptide 180-199 in sera were found in TNF-alpha KO mice with EAN. In conclusion, TNF-alpha deficiency attenuates EAN via altering the M1/M2 balance of macrophages. PMID- 22666472 TI - Comparative analysis of gene expression level by quantitative real-time PCR has limited application in objects with different morphology. AB - qRT-PCR is a generally acknowledged method for gene expression analysis due to its precision and reproducibility. However, it is well known that the accuracy of qRT-PCR data varies greatly depending on the experimental design and data analysis. Recently, a set of guidelines has been proposed that aims to improve the reliability of qRT-PCR. However, there are additional factors that have not been taken into consideration in these guidelines that can seriously affect the data obtained using this method. In this study, we report the influence that object morphology can have on qRT-PCR data. We have used a number of Arabidopsis thaliana mutants with altered floral morphology as models for this study. These mutants have been well characterised (including in terms of gene expression levels and patterns) by other techniques. This allows us to compare the results from the qRT-PCR with the results inferred from other methods. We demonstrate that the comparison of gene expression levels in objects that differ greatly in their morphology can lead to erroneous results. PMID- 22666473 TI - Beyond repair foci: DNA double-strand break repair in euchromatic and heterochromatic compartments analyzed by transmission electron microscopy. AB - PURPOSE: DNA double-strand breaks (DSBs) generated by ionizing radiation pose a serious threat to the preservation of genetic and epigenetic information. The known importance of local chromatin configuration in DSB repair raises the question of whether breaks in different chromatin environments are recognized and repaired by the same repair machinery and with similar efficiency. An essential step in DSB processing by non-homologous end joining is the high-affinity binding of Ku70-Ku80 and DNA-PKcs to double-stranded DNA ends that holds the ends in physical proximity for subsequent repair. METHODS AND MATERIALS: Using transmission electron microscopy to localize gold-labeled pKu70 and pDNA-PKcs within nuclear ultrastructure, we monitored the formation and repair of actual DSBs within euchromatin (electron-lucent) and heterochromatin (electron-dense) in cortical neurons of irradiated mouse brain. RESULTS: While DNA lesions in euchromatin (characterized by two pKu70-gold beads, reflecting the Ku70-Ku80 heterodimer) are promptly sensed and rejoined, DNA packaging in heterochromatin appears to retard DSB processing, due to the time needed to unravel higher-order chromatin structures. Complex pKu70-clusters formed in heterochromatin (consisting of 4 or >= 6 gold beads) may represent multiple breaks in close proximity caused by ionizing radiation of highly-compacted DNA. All pKu70 clusters disappeared within 72 hours post-irradiation, indicating efficient DSB rejoining. However, persistent 53BP1 clusters in heterochromatin (comprising >= 10 gold beads), occasionally co-localizing with gammaH2AX, but not pKu70 or pDNA PKcs, may reflect incomplete or incorrect restoration of chromatin structure rather than persistently unrepaired DNA damage. DISCUSSION: Higher-order organization of chromatin determines the accessibility of DNA lesions to repair complexes, defining how readily DSBs are detected and processed. DNA lesions in heterochromatin appear to be more complex, with multiple breaks in spatial vicinity inducing severe chromatin disruptions. Imperfect restoration of chromatin configurations may leave DSB-induced epigenetic memory of damage with potentially pathological repercussions. PMID- 22666475 TI - Synchronizing allelic effects of opposing quantitative trait loci confirmed a major epistatic interaction affecting acute lung injury survival in mice. AB - Increased oxygen (O(2)) levels help manage severely injured patients, but too much for too long can cause acute lung injury (ALI), acute respiratory distress syndrome (ARDS) and even death. In fact, continuous hyperoxia has become a prototype in rodents to mimic salient clinical and pathological characteristics of ALI/ARDS. To identify genes affecting hyperoxia-induced ALI (HALI), we previously established a mouse model of differential susceptibility. Genetic analysis of backcross and F(2) populations derived from sensitive (C57BL/6J; B) and resistant (129X1/SvJ; X1) inbred strains identified five quantitative trait loci (QTLs; Shali1-5) linked to HALI survival time. Interestingly, analysis of these recombinant populations supported opposite within-strain effects on survival for the two major-effect QTLs. Whereas Shali1 alleles imparted the expected survival time effects (i.e., X1 alleles increased HALI resistance and B alleles increased sensitivity), the allelic effects of Shali2 were reversed (i.e., X1 alleles increased HALI sensitivity and B alleles increased resistance). For in vivo validation of these inverse allelic effects, we constructed reciprocal congenic lines to synchronize the sensitivity or resistance alleles of Shali1 and Shali2 within the same strain. Specifically, B-derived Shali1 or Shali2 QTL regions were transferred to X1 mice and X1-derived QTL segments were transferred to B mice. Our previous QTL results predicted that substituting Shali1 B alleles onto the resistant X1 background would add sensitivity. Surprisingly, not only were these mice more sensitive than the resistant X1 strain, they were more sensitive than the sensitive B strain. In stark contrast, substituting the Shali2 interval from the sensitive B strain onto the X1 background markedly increased the survival time. Reciprocal congenic lines confirmed the opposing allelic effects of Shali1 and Shali2 on HALI survival time and provide unique models to identify their respective quantitative trait genes and to critically assess the apparent bidirectional epistatic interactions between these major-effect loci. PMID- 22666474 TI - Inhibition of soluble tumor necrosis factor ameliorates synaptic alterations and Ca2+ dysregulation in aged rats. AB - The role of tumor necrosis factor alpha (TNF) in neural function has been investigated extensively in several neurodegenerative conditions, but rarely in brain aging, where cognitive and physiologic changes are milder and more variable. Here, we show that protein levels for TNF receptor 1 (TNFR1) are significantly elevated in the hippocampus relative to TNF receptor 2 (TNFR2) in aged (22 months) but not young adult (6 months) Fischer 344 rats. To determine if altered TNF/TNFR1 interactions contribute to key brain aging biomarkers, aged rats received chronic (4-6 week) intracranial infusions of XPro1595: a soluble dominant negative TNF that preferentially inhibits TNFR1 signaling. Aged rats treated with XPro1595 showed improved Morris Water Maze performance, reduced microglial activation, reduced susceptibility to hippocampal long-term depression, increased protein levels for the GluR1 type glutamate receptor, and lower L-type voltage sensitive Ca(2+) channel (VSCC) activity in hippocampal CA1 neurons. The results suggest that diverse functional changes associated with brain aging may arise, in part, from selective alterations in TNF signaling. PMID- 22666477 TI - Metagenomic and metatranscriptomic analysis of microbial community structure and gene expression of activated sludge. AB - The present study applied both metagenomic and metatranscriptomic approaches to characterize microbial structure and gene expression of an activated sludge community from a municipal wastewater treatment plant in Hong Kong. DNA and cDNA were sequenced by Illumina Hi-seq2000 at a depth of 2.4 Gbp. Taxonomic analysis by MG-RAST showed bacteria were dominant in both DNA and cDNA datasets. The taxonomic profile obtained by BLAST against SILVA SSUref database and annotation by MEGAN showed that activated sludge was dominated by Proteobacteria, Actinobacteria, Bacteroidetes, Firmicutes and Verrucomicrobia phyla in both DNA and cDNA datasets. Global gene expression annotation based on KEGG metabolism pathway displayed slight disagreement between the DNA and cDNA datasets. Further gene expression annotation focusing on nitrogen removal revealed that denitrification-related genes sequences dominated in both DNA and cDNA datasets, while nitrifying genes were also expressed in relative high levels. Specially, ammonia monooxygenase and hydroxylamine oxidase demonstrated the high cDNA/DNA ratios in the present study, indicating strong nitrification activity. Enzyme subunits gene sequences annotation discovered that subunits of ammonia monooxygenase (amoA, amoB, amoC) and hydroxylamine oxygenase had higher expression levels compared with subunits of the other enzymes genes. Taxonomic profiles of selected enzymes (ammonia monooxygenase and hydroxylamine oxygenase) showed that ammonia-oxidizing bacteria present mainly belonged to Nitrosomonas and Nitrosospira species and no ammonia-oxidizing Archaea sequences were detected in both DNA and cDNA datasets. PMID- 22666476 TI - Cytoplasmic fungal lipases release fungicides from ultra-deformable vesicular drug carriers. AB - The Transfersome(r) is a lipid vesicle that contains membrane softeners, such as Tween 80, to make it ultra-deformable. This feature makes the Transfersome(r) an efficient carrier for delivery of therapeutic drugs across the skin barrier. It was reported that TDT 067 (a topical formulation of 15 mg/ml terbinafine in Transfersome(r) vesicles) has a much more potent antifungal activity in vitro compared with conventional terbinafine, which is a water-insoluble fungicide. Here we use ultra-structural studies and live imaging in a model fungus to describe the underlying mode of action. We show that terbinafine causes local collapse of the fungal endoplasmic reticulum, which was more efficient when terbinafine was delivered in Transfersome(r) vesicles (TFVs). When applied in liquid culture, fluorescently labeled TFVs rapidly entered the fungal cells (T(1/2)~2 min). Entry was F-actin- and ATP-independent, indicating that it is a passive process. Ultra-structural studies showed that passage through the cell wall involves significant deformation of the vesicles, and depends on a high concentration of the surfactant Tween 80 in their membrane. Surprisingly, the TFVs collapsed into lipid droplets after entry into the cell and the terbinafine was released from their interior. With time, the lipid bodies were metabolized in an ATP-dependent fashion, suggesting that cytosolic lipases attack and degrade intruding TFVs. Indeed, the specific monoacylglycerol lipase inhibitor URB602 prevented Transfersome(r) degradation and neutralized the cytotoxic effect of Transfersome(r)-delivered terbinafine. These data suggest that (a) Transfersomes deliver the lipophilic fungicide Terbinafine to the fungal cell wall, (b) the membrane softener Tween 80 allows the passage of the Transfersomes into the fungal cell, and (c) fungal lipases digest the invading Transfersome(r) vesicles thereby releasing their cytotoxic content. As this mode of action of Transfersomes is independent of the drug cargo, these results demonstrate the potential of Transfersomes in the treatment of all fungal diseases. PMID- 22666478 TI - Phylogeography of the South China field mouse (Apodemus draco) on the southeastern Tibetan Plateau reveals high genetic diversity and glacial refugia. AB - The southeastern margin of the Tibetan Plateau (SEMTP) is a particularly interesting region due to its topographic complexity and unique geologic history, but phylogeographic studies that focus on this region are rare. In this study, we investigated the phylogeography of the South China field mouse, Apodemus draco, in order to assess the role of geologic and climatic events on the Tibetan Plateau in shaping its genetic structure. We sequenced mitochondrial cytochrome b (cyt b) sequences in 103 individuals from 47 sampling sites. In addition, 23 cyt b sequences were collected from GenBank for analyses. Phylogenetic, demographic and landscape genetic methods were conducted. Seventy-six cyt b haplotypes were found and the genetic diversity was extremely high (pi = 0.0368; h = 0.989). Five major evolutionary clades, based on geographic locations, were identified. Demographic analyses implied subclade 1A and subclade 1B experienced population expansions at about 0.052-0.013 Mya and 0.014-0.004 Mya, respectively. The divergence time analysis showed that the split between clade 1 and clade 2 occurred 0.26 Mya, which fell into the extensive glacial period (EGP, 0.5-0.17 Mya). The divergence times of other main clades (2.20-0.55 Mya) were congruent with the periods of the Qingzang Movement (3.6-1.7 Mya) and the Kun-Huang Movement (1.2-0.6 Mya), which were known as the most intense uplift events in the Tibetan Plateau. Our study supported the hypothesis that the SEMTP was a large late Pleistocene refugium, and further inferred that the Gongga Mountain Region and Hongya County were glacial refugia for A. draco in clade 1. We hypothesize that the evolutionary history of A. draco in the SEMTP primarily occurred in two stages. First, an initial divergence would have been shaped by uplift events of the Tibetan Plateau. Then, major glaciations in the Pleistocene added complexity to its demographic history and genetic structure. PMID- 22666479 TI - The ArcB leucine zipper domain is required for proper ArcB signaling. AB - The Arc two-component system modulates the expression of numerous genes in response to respiratory growth conditions. This system comprises ArcA as the response regulator and ArcB as the sensor kinase. ArcB is a tripartite histidine kinase whose activity is regulated by the oxidation of two cytosol-located redox active cysteine residues that participate in intermolecular disulfide bond formation. Here, we report that the ArcB protein segment covering residues 70 121, fulfills the molecular characteristics of a leucine zipper containing coiled coil structure. Also, mutational analyses of this segment reveal three different phenotypical effects to be distributed along the coiled coil structure of ArcB, demonstrating that this motif is essential for proper ArcB signaling. PMID- 22666480 TI - Human mesenchymal stem cells protect human islets from pro-inflammatory cytokines. AB - Transplantation of human islets is an attractive alternative to daily insulin injections for patients with type 1 diabetes. However, the majority of islet recipients lose graft function within five years. Inflammation is a primary contributor to graft loss, and inhibiting pro-inflammatory cytokine activity can reverse inflammation mediated dysfunction of islet grafts. As mesenchymal stem cells (MSCs) possess numerous immunoregulatory properties, we hypothesized that MSCs could protect human islets from pro-inflammatory cytokines. Five hundred human islets were co-cultured with 0.5 or 1.0 * 10(6) human MSCs derived from bone marrow or pancreas for 24 hours followed by 48 hour exposure to interferon gamma, tumor necrosis factor-alpha and interleukin 1beta. Controls include islets cultured alone (+/- cytokines) and with human dermal fibroblasts (+/- cytokines). For all conditions, glucose stimulated insulin secretion (GSIS), total islet cellular insulin content, islet beta cell apoptosis, and potential cytoprotective factors secreted in the culture media were determined. Cytokine exposure disrupted human islet GSIS based on stimulation index and percentage insulin secretion. Conversely, culture with 1.0 * 10(6) bMSCs preserved GSIS from cytokine treated islets. Protective effects were not observed with fibroblasts, indicating that preservation of human islet GSIS after exposure to pro inflammatory cytokines is MSC dependent. Islet beta cell apoptosis was observed in the presence of cytokines; however, culture of bMSCs with islets prevented beta cell apoptosis after cytokine treatment. Hepatocyte growth factor (HGF) as well as matrix metalloproteinases 2 and 9 were also identified as putative secreted cytoprotective factors; however, other secreted factors likely play a role in protection. This study, therefore, demonstrates that MSCs may be beneficial for islet engraftment by promoting cell survival and reduced inflammation. PMID- 22666481 TI - Studies on the restriction of murine leukemia viruses by mouse APOBEC3. AB - APOBEC3 proteins function to restrict the replication of retroviruses. One mechanism of this restriction is deamination of cytidines to uridines in (-) strand DNA, resulting in hypermutation of guanosines to adenosines in viral (+) strands. However, Moloney murine leukemia virus (MoMLV) is partially resistant to restriction by mouse APOBEC3 (mA3) and virtually completely resistant to mA3 induced hypermutation. In contrast, the sequences of MLV genomes that are in mouse DNA suggest that they were susceptible to mA3-induced deamination when they infected the mouse germline. We tested the possibility that sensitivity to mA3 restriction and to deamination resides in the viral gag gene. We generated a chimeric MLV in which the gag gene was from an endogenous MLV in the mouse germline, while the remainder of the viral genome was from MoMLV. This chimera was fully infectious but its response to mA3 was indistinguishable from that of MoMLV. Thus, the Gag protein does not seem to control the sensitivity of MLVs to mA3. We also found that MLVs inactivated by mA3 do not synthesize viral DNA upon infection; thus mA3 restriction of MLV occurs before or at reverse transcription. In contrast, HIV-1 restricted by mA3 and MLVs restricted by human APOBEC3G do synthesize DNA; these DNAs exhibit APOBEC3-induced hypermutation. PMID- 22666482 TI - The interaction pattern of murine serum ficolin-A with microorganisms. AB - The ficolins are soluble pattern recognition molecules in the lectin pathway of complement, but the spectrum and mode of interaction with pathogens are largely unknown. In this study, we investigated the binding properties of the murine serum ficolin-A towards a panel of different clinical relevant microorganisms (N = 45) and compared the binding profile with human serum ficolin-2 and ficolin-3. Ficolin-A was able to bind Gram-positive bacteria strains including E. faecalis, L. monocytogenes and some S. aureus strains, but not to the investigated S. agalactiae (Group B streptococcus) strains. Regarding Gram-negative bacteria ficolin-A was able to bind to some E. coli and P. aeruginosa strains, but not to the investigated Salmonella strains. Of particular interest ficolin-A bound strongly to the pathogenic E. coli, O157:H7 and O149 strains, but it did not bind to the non-pathogenic E. coli, ATCC 25922 strain. Additionally, ficolin-A was able to bind purified LPS from these pathogenic strains. Furthermore, ficolin-A bound to a clinical isolate of the fungus A. fumigatus. In general ficolin-2 showed similar selective binding spectrum towards pathogenic microorganisms as observed for ficolin-A indicating specific pathophysiological roles of these molecules in host defence. In contrast, ficolin-3 did not bind to any of the investigated microorganisms and the anti-microbial role of ficolin-3 still remains elusive. PMID- 22666484 TI - Seroepidemiology of human bocavirus infection in Jamaica. AB - BACKGROUND: Human bocavirus (HBoV) is a newly identified human parvovirus. HBoV is associated with upper and lower respiratory tract infections and gastroenteritis in children. Little is known about the seroepidemiology of HBoV in populations in the Caribbean. METHODS: In a cross-sectional study conducted at the University Hospital of the West Indies in Kingston, Jamaica, 287 blood samples were collected from pediatric patients and tested for the presence of HBoV-specific antibody using a virus-like-particle based enzyme-linked immunosorbent assay (ELISA). RESULTS: HBoV-specific antibodies were found to be present in 220/287 (76.7%) of samples collected from the pediatric population. Seroprevalence of HBoV was highest in those >=2 years old. The seroepidemiological profile suggests that most children are exposed to HBoV during the first two years of life in Jamaica. CONCLUSION: HBoV infection is common in children in Jamaica. HBoV seroprevalence rates in the Caribbean are similar to those previously reported in other areas of the world. PMID- 22666483 TI - Aldosterone inhibits the fetal program and increases hypertrophy in the heart of hypertensive mice. AB - BACKGROUND: Arterial hypertension (AH) induces cardiac hypertrophy and reactivation of "fetal" gene expression. In rodent heart, alpha-Myosin Heavy Chain (MyHC) and its micro-RNA miR-208a regulate the expression of beta-MyHC and of its intronic miR-208b. However, the role of aldosterone in these processes remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: RT-PCR and western-blot were used to investigate the genes modulated by arterial hypertension and cardiac hyperaldosteronism. We developed a model of double-transgenic mice (AS-Ren) with cardiac hyperaldosteronism (AS mice) and systemic hypertension (Ren). AS-Ren mice had increased (x2) angiotensin II in plasma and increased (x2) aldosterone in heart. Ren and AS-Ren mice had a robust and similar hypertension (+70%) versus their controls. Anatomical data and echocardiography showed a worsening of cardiac hypertrophy (+41%) in AS-Ren mice (P<0.05 vs Ren). The increase of ANP (x 2.5; P<0.01) mRNA observed in Ren mice was blunted in AS-Ren mice. This non induction of antitrophic natriuretic peptides may be involved in the higher trophic cardiac response in AS-Ren mice, as indicated by the markedly reduced cardiac hypertrophy in ANP-infused AS-Ren mice for one month. Besides, the AH induced increase of betaMyHC and its intronic miRNA-208b was prevented in AS-Ren. The inhibition of miR 208a (-75%, p<0.001) in AS-Ren mice compared to AS was associated with increased Sox 6 mRNA (x 1.34; p<0.05), an inhibitor of betaMyHC transcription. Eplerenone prevented all aldosterone-dependent effects. CONCLUSIONS/SIGNIFICANCE: Our results indicate that increased aldosterone in heart inhibits the induction of atrial natriuretic peptide expression, via the mineralocorticoid receptor. This worsens cardiac hypertrophy without changing blood pressure. Moreover, this work reveals an original aldosterone-dependent inhibition of miR-208a in hypertension, resulting in the inhibition of beta myosin heavy chain expression through the induction of its transcriptional repressor Sox6. Thus, aldosterone inhibits the fetal program and increases cardiac hypertrophy in hypertensive mice. PMID- 22666486 TI - Fluorescence polarization and fluctuation analysis monitors subunit proximity, stoichiometry, and protein complex hydrodynamics. AB - Forster resonance energy transfer (FRET) microscopy is frequently used to study protein interactions and conformational changes in living cells. The utility of FRET is limited by false positive and negative signals. To overcome these limitations we have developed Fluorescence Polarization and Fluctuation Analysis (FPFA), a hybrid single-molecule based method combining time-resolved fluorescence anisotropy (homo-FRET) and fluorescence correlation spectroscopy. Using FPFA, homo-FRET (a 1-10 nm proximity gauge), brightness (a measure of the number of fluorescent subunits in a complex), and correlation time (an attribute sensitive to the mass and shape of a protein complex) can be simultaneously measured. These measurements together rigorously constrain the interpretation of FRET signals. Venus based control-constructs were used to validate FPFA. The utility of FPFA was demonstrated by measuring in living cells the number of subunits in the alpha-isoform of Venus-tagged calcium-calmodulin dependent protein kinase-II (CaMKIIalpha) holoenzyme. Brightness analysis revealed that the holoenzyme has, on average, 11.9 +/- 1.2 subunit, but values ranged from 10-14 in individual cells. Homo-FRET analysis simultaneously detected that catalytic domains were arranged as dimers in the dodecameric holoenzyme, and this paired organization was confirmed by quantitative hetero-FRET analysis. In freshly prepared cell homogenates FPFA detected only 10.2 +/- 1.3 subunits in the holoenzyme with values ranging from 9-12. Despite the reduction in subunit number, catalytic domains were still arranged as pairs in homogenates. Thus, FPFA suggests that while the absolute number of subunits in an auto-inhibited holoenzyme might vary from cell to cell, the organization of catalytic domains into pairs is preserved. PMID- 22666485 TI - Vibrio cholerae VexH encodes a multiple drug efflux pump that contributes to the production of cholera toxin and the toxin co-regulated pilus. AB - The resistance-nodulation-division (RND) efflux systems are ubiquitous transporters that function in antimicrobial resistance. Recent studies showed that RND systems were required for virulence factor production in Vibrio cholerae. The V. cholerae genome encodes six RND efflux systems. Three of the RND systems (VexB, VexD, and VexK) were previously shown to be redundant for in vitro resistance to bile acids and detergents. A mutant lacking the VexB, VexD, and VexK RND pumps produced wild-type levels of cholera toxin (CT) and the toxin co regulated pilus (TCP) and was moderately attenuated for intestinal colonization. In contrast, a RND negative mutant produced significantly reduced amounts of CT and TCP and displayed a severe colonization defect. This suggested that one or more of the three uncharacterized RND efflux systems (i.e. VexF, VexH, and VexM) were required for pathogenesis. In this study, a genetic approach was used to generate a panel of V. cholerae RND efflux pump mutants in order to determine the function of VexH in antimicrobial resistance, virulence factor production, and intestinal colonization. VexH contributed to in vitro antimicrobial resistance and exhibited a broad substrate specificity that was redundant with the VexB, VexD, and VexK RND efflux pumps. These four efflux pumps were responsible for in vitro antimicrobial resistance and were required for virulence factor production and intestinal colonization. Mutation of the VexF and/or VexM efflux pumps did not affect in vitro antimicrobial resistance, but did negatively affect CT and TCP production. Collectively, our results demonstrate that the V. cholerae RND efflux pumps have redundant functions in antimicrobial resistance and virulence factor production. This suggests that the RND efflux systems contribute to V. cholerae pathogenesis by providing the bacterium with protection against antimicrobial compounds that are present in the host and by contributing to the regulated expression of virulence factors. PMID- 22666487 TI - Mdm2 RING mutation enhances p53 transcriptional activity and p53-p300 interaction. AB - The p53 transcription factor and tumor suppressor is regulated primarily by the E3 ubiquitin ligase Mdm2, which ubiquitinates p53 to target it for proteasomal degradation. Aside from its ubiquitin ligase function, Mdm2 has been believed to be capable of suppressing p53's transcriptional activity by binding with and masking the transactivation domain of p53. The ability of Mdm2 to restrain p53 activity by binding alone, without ubiquitination, was challenged by a 2007 study using a knockin mouse harboring a single cysteine-to-alanine point mutation (C462A) in Mdm2's RING domain. Mouse embryonic fibroblasts with this mutation, which abrogates Mdm2's E3 ubiquitin ligase activity without affecting its ability to bind with p53, were unable to suppress p53 activity. In this study, we utilized the Mdm2(C462A) mouse model to characterize in further detail the role of Mdm2's RING domain in the control of p53. Here, we show in vivo that the Mdm2(C462A) protein not only fails to suppress p53, but compared to the complete absence of Mdm2, Mdm2(C462A) actually enhances p53 transcriptional activity toward p53 target genes p21/CDKN1A, MDM2, BAX, NOXA, and 14-3-3sigma. In addition, we found that Mdm2(C462A) facilitates the interaction between p53 and the acetyltransferase CBP/p300, and it fails to heterodimerize with its homolog and sister regulator of p53, Mdmx, suggesting that a fully intact RING domain is required for Mdm2's inhibition of the p300-p53 interaction and for its interaction with Mdmx. These findings help us to better understand the complex regulation of the Mdm2-p53 pathway and have important implications for chemotherapeutic agents targeting Mdm2, as they suggest that inhibition of Mdm2's E3 ubiquitin ligase activity may be sufficient for increasing p53 activity in vivo, without the need to block Mdm2-p53 binding. PMID- 22666488 TI - The relationship between dioxin-like polychlorobiphenyls and IGF-I serum levels in healthy adults: evidence from a cross-sectional study. AB - OBJECTIVE: Insulin-like growth factor I (IGF-I) and dioxin-like polychlorobiphenyls (DL-PCBs) have been associated with the pathogenesis of several diseases like cancer, diabetes and growth disorders. Because it has been suggested that organohalogenated contaminants could influence IGF-I levels in adults, the potential relationship between DL-PCBs and IGF-I serum levels was studied in 456 healthy adults from a representative sample of the general population of the Canary Islands (Spain). DESIGN: Free circulating serum levels of IGF-I and IGFBP-3 were measured through an ELISA methodology, while the serum levels of the 12 DL-PCBs congeners (IUPAC numbers # 77, 81, 105, 114, 118, 123, 126, 156, 157, 167, 169, and 189) were measured by gas chromatography/mass spectrometry (GC-MS). RESULTS: DL-PCBs 156 and 167, Total DL-PCBs body burden (?PCBs: sum over the 12 measured DL-PCBs), and Total toxic burden (in terms of toxic equivalence to dioxins: ?TEQs) showed a trend of inverse association with IGF-I serum levels in the whole studied population. After adjusting for potential confounders, including gender, body mass index (BMI), age, and IGF-binding protein-3 (IGFBP-3), younger (18-45 years) women with lower BMI (<27 kg/m(2)) and detectable levels of DL-PCB-156 showed significantly lower IGF-I levels than those in the same age and BMI subgroup with non-detectable levels of DL-PCB-156 (p<0.001). Similarly, ?PCBs and ?TEQs showed a tendency to an inverse association with IGF-I levels in the same group of women (p=0.017 and p=0.019 respectively). CONCLUSIONS: These findings suggest that DL-PCBs could be involved in the regulation of the IGF-system in a way possibly influenced by gender, age and BMI. Although these results should be interpreted with caution, such circumstances could contribute to explain the development of diseases associated to the IGF system. PMID- 22666489 TI - Sliding window analyses for optimal selection of mini-barcodes, and application to 454-pyrosequencing for specimen identification from degraded DNA. AB - DNA barcoding remains a challenge when applied to diet analyses, ancient DNA studies, environmental DNA samples and, more generally, in any cases where DNA samples have not been adequately preserved. Because the size of the commonly used barcoding marker (COI) is over 600 base pairs (bp), amplification fails when the DNA molecule is degraded into smaller fragments. However, relevant information for specimen identification may not be evenly distributed along the barcoding region, and a shorter target can be sufficient for identification purposes. This study proposes a new, widely applicable, method to compare the performance of all potential 'mini-barcodes' for a given molecular marker and to objectively select the shortest and most informative one. Our method is based on a sliding window analysis implemented in the new R package SPIDER (Species IDentity and Evolution in R). This method is applicable to any taxon and any molecular marker. Here, it was tested on earthworm DNA that had been degraded through digestion by carnivorous landsnails. A 100 bp region of 16 S rDNA was selected as the shortest informative fragment (mini-barcode) required for accurate specimen identification. Corresponding primers were designed and used to amplify degraded earthworm (prey) DNA from 46 landsnail (predator) faeces using 454 pyrosequencing. This led to the detection of 18 earthworm species in the diet of the snail. We encourage molecular ecologists to use this method to objectively select the most informative region of the gene they aim to amplify from degraded DNA. The method and tools provided here, can be particularly useful (1) when dealing with degraded DNA for which only small fragments can be amplified, (2) for cases where no consensus has yet been reached on the appropriate barcode gene, or (3) to allow direct analysis of short reads derived from massively parallel sequencing without the need for bioinformatic consolidation. PMID- 22666490 TI - Investigation of the enteric pathogenic potential of oral Campylobacter concisus strains isolated from patients with inflammatory bowel disease. AB - BACKGROUND: Campylobacter concisus, a bacterium colonizing the human oral cavity, has been shown to be associated with inflammatory bowel disease (IBD). This study investigated if patients with IBD are colonized with specific oral C. concisus strains that have potential to cause enteric diseases. METHODOLOGY: Seventy oral and enteric C. concisus isolates obtained from eight patients with IBD and six controls were examined for housekeeping genes by multilocus sequence typing (MLST), Caco2 cell invasion by gentamicin-protection-assay, protein analysis by mass spectrometry and SDS-PAGE, and morphology by scanning electron microscopy. The whole genome sequenced C. concisus strain 13826 which was isolated from an individual with bloody diarrhea was included in MLST analysis. PRINCIPAL FINDINGS: MLST analysis showed that 87.5% of individuals whose C. concisus belonged to Cluster I had inflammatory enteric diseases (six IBD and one with bloody diarrhea), which was significantly higher than that in the remaining individuals (28.6%) (P<0.05). Enteric invasive C. concisus (EICC) oral strain was detected in 50% of patients with IBD and none of the controls. All EICC strains were in Cluster 1. The C. concisus strain colonizing intestinal tissues of patient No. 1 was closely related to the oral C. concisus strain from patient No. 6 and had gene recombination with the patient's own oral C. concisus. The oral and intestinal C. concisus strains of patient No. 3 were the same strain. Some individuals were colonized with multiple oral C. concisus strains that have undergone natural recombination. CONCLUSIONS: This study provides the first evidence that patients with IBD are colonized with specific oral C. concisus strains, with some being EICC strains. C. concisus colonizing intestinal tissues of patients with IBD at least in some instances results from an endogenous colonization of the patient's oral C. concisus and that C. concisus strains undergo natural recombination. PMID- 22666491 TI - FunFOLDQA: a quality assessment tool for protein-ligand binding site residue predictions. AB - The estimation of prediction quality is important because without quality measures, it is difficult to determine the usefulness of a prediction. Currently, methods for ligand binding site residue predictions are assessed in the function prediction category of the biennial Critical Assessment of Techniques for Protein Structure Prediction (CASP) experiment, utilizing the Matthews Correlation Coefficient (MCC) and Binding-site Distance Test (BDT) metrics. However, the assessment of ligand binding site predictions using such metrics requires the availability of solved structures with bound ligands. Thus, we have developed a ligand binding site quality assessment tool, FunFOLDQA, which utilizes protein feature analysis to predict ligand binding site quality prior to the experimental solution of the protein structures and their ligand interactions. The FunFOLDQA feature scores were combined using: simple linear combinations, multiple linear regression and a neural network. The neural network produced significantly better results for correlations to both the MCC and BDT scores, according to Kendall's tau, Spearman's rho and Pearson's r correlation coefficients, when tested on both the CASP8 and CASP9 datasets. The neural network also produced the largest Area Under the Curve score (AUC) when Receiver Operator Characteristic (ROC) analysis was undertaken for the CASP8 dataset. Furthermore, the FunFOLDQA algorithm incorporating the neural network, is shown to add value to FunFOLD, when both methods are employed in combination. This results in a statistically significant improvement over all of the best server methods, the FunFOLD method (6.43%), and one of the top manual groups (FN293) tested on the CASP8 dataset. The FunFOLDQA method was also found to be competitive with the top server methods when tested on the CASP9 dataset. To the best of our knowledge, FunFOLDQA is the first attempt to develop a method that can be used to assess ligand binding site prediction quality, in the absence of experimental data. PMID- 22666493 TI - Plant chemistry and local adaptation of a specialized folivore. AB - Local adaptation is central for creating and maintaining spatial variation in plant-herbivore interactions. Short-lived insect herbivores feeding on long-lived plants are likely to adapt to their local host plants, because of their short generation time, poor dispersal, and geographically varying selection due to variation in plant defences. In a reciprocal feeding trial, we investigated the impact of geographic variation in plant secondary chemistry of a long-lived plant, Vincetoxicum hirundinaria, on among-population variation in local adaptation of a specialist leaf-feeding herbivore, Abrostola asclepiadis. The occurrence and degree of local adaptation varied among populations. This variation correlated with qualitative and quantitative differences in plant chemistry among the plant populations. These findings provide insights into the mechanisms driving variation in local adaptation in this specialized plant herbivore interaction. PMID- 22666492 TI - Characterisation of the cell line HC-AFW1 derived from a pediatric hepatocellular carcinoma. AB - Current treatment of paediatric hepatocellular carcinoma (HCC) is often inefficient due to advanced disease at diagnosis and resistance to common drugs. The aim of this study was to generate a cell line derived from a paediatric HCC in order to expand research in this field. We established the HC-AFW1 cell line from a liver neoplasm of a 4-year-old boy through culturing of primary tumor specimens. The cell line has been stable for over one year of culturing and has a doubling time of 40 h. The tumour cells have an epithelial histology and express HCC-associated proteins such as Alpha-fetoprotein (AFP), Glypican 3, E-cadherin, CD10, CD326, HepPar1 and Vimentin. Forty-nine amino acids in exon 3 of beta Catenin that involve the phosphorylation sites of GSK3 were absent and beta Catenin is detectable in the cell nuclei. Cytogenetic analysis revealed large anomalies in the chromosomal map. Several alterations of gene copy numbers were detected by genome-wide SNP array. Among the different drugs tested, cisplatin and irinotecan showed effective inhibition of tumour cell growth in a proliferation assay at concentrations below 5 ug/ml. Subcutaneous xenotransplantation of HC-AFW1 cells into NOD/SCID mice resulted in fast growing dedifferentiated tumours with high levels of serum AFP. Histological analyses of the primary tumour and xenografts included national and international expert pathological review. Consensus reading characterised the primary tumour and the HC-AFW1-derived tumours as HCC. HC-AFW1 is the first cell line derived from a paediatric HCC without a background of viral hepatitis or cirrhosis and represents a valuable tool for investigating the biology of and therapeutic strategies for childhood HCC. PMID- 22666494 TI - Posture does not matter! Paw usage and grasping paw preference in a small-bodied rooting quadrupedal mammal. AB - BACKGROUND: Recent results in birds, marsupials, rodents and nonhuman primates suggest that phylogeny and ecological factors such as body size, diet and postural habit of a species influence limb usage and the direction and strength of limb laterality. To examine to which extent these findings can be generalised to small-bodied rooting quadrupedal mammals, we studied trees shrews (Tupaia belangeri). METHODOLOGY/PRINCIPAL FINDINGS: We established a behavioural test battery for examining paw usage comparable to small-bodied primates and tested 36 Tupaia belangeri. We studied paw usage in a natural foraging situation (simple food grasping task) and measured the influence of varying postural demands (triped, biped, cling, sit) on paw preferences by applying a forced-food grasping task similar to other small-bodied primates. Our findings suggest that rooting tree shrews prefer mouth over paw usage to catch food in a natural foraging situation. Moreover, we demonstrated that despite differences in postural demand, tree shrews show a strong and consistent individual paw preference for grasping across different tasks, but no paw preference at a population level. CONCLUSIONS/SIGNIFICANCE: Tree shrews showed less paw usage than small-bodied quadrupedal and arboreal primates, but the same paw preference. Our results confirm that individual paw preferences remain constant irrespective of postural demand in some small-bodied quadrupedal non primate and primate mammals which do not require fine motoric control for manipulating food items. Our findings suggest that the lack of paw/hand preference for grasping food at a population level is a universal pattern among those species and that the influence of postural demand on manual lateralisation in quadrupeds may have evolved in large bodied species specialised in fine manipulations of food items. PMID- 22666495 TI - Low-level laser irradiation stimulates tenocyte migration with up-regulation of dynamin II expression. AB - Low-level laser therapy (LLLT) is commonly used to treat sports-related tendinopathy or tendon injury. Tendon healing requires tenocyte migration to the repair site, followed by proliferation and synthesis of the extracellular matrix. This study was designed to determine the effect of laser on tenocyte migration. Furthermore, the correlation between this effect and expression of dynamin 2, a positive regulator of cell motility, was also investigated. Tenocytes intrinsic to rat Achilles tendon were treated with low-level laser (660 nm with energy density at 1.0, 1.5, and 2.0 J/cm(2)). Tenocyte migration was evaluated by an in vitro wound healing model and by transwell filter migration assay. The messenger RNA (mRNA) and protein expressions of dynamin 2 were determined by reverse transcription/real-time polymerase chain reaction (real-time PCR) and Western blot analysis respectively. Immunofluorescence staining was used to evaluate the dynamin 2 expression in tenocytes. Tenocytes with or without laser irradiation was treated with dynasore, a dynamin competitor and then underwent transwell filter migration assay. In vitro wound model revealed that more tenocytes with laser irradiation migrated across the wound border to the cell-free zone. Transwell filter migration assay confirmed that tenocyte migration was enhanced dose-dependently by laser. Real-time PCR and Western-blot analysis demonstrated that mRNA and protein expressions of dynamin 2 were up-regulated by laser irradiation dose-dependently. Confocal microscopy showed that laser enhanced the expression of dynamin 2 in cytoplasm of tenocytes. The stimulation effect of laser on tenocytes migration was suppressed by dynasore. In conclusion, low-level laser irradiation stimulates tenocyte migration in a process that is mediated by up-regulation of dynamin 2, which can be suppressed by dynasore. PMID- 22666496 TI - Genome-wide study of gene variants associated with differential cardiovascular event reduction by pravastatin therapy. AB - Statin therapy reduces the risk of coronary heart disease (CHD), however, the person-to-person variability in response to statin therapy is not well understood. We have investigated the effect of genetic variation on the reduction of CHD events by pravastatin. First, we conducted a genome-wide association study of 682 CHD cases from the Cholesterol and Recurrent Events (CARE) trial and 383 CHD cases from the West of Scotland Coronary Prevention Study (WOSCOPS), two randomized, placebo-controlled studies of pravastatin. In a combined case-only analysis, 79 single nucleotide polymorphisms (SNPs) were associated with differential CHD event reduction by pravastatin according to genotype (P<0.0001), and these SNPs were analyzed in a second stage that included cases as well as non cases from CARE and WOSCOPS and patients from the PROspective Study of Pravastatin in the Elderly at Risk/PHArmacogenomic study of Statins in the Elderly at risk for cardiovascular disease (PROSPER/PHASE), a randomized placebo controlled study of pravastatin in the elderly. We found that one of these SNPs (rs13279522) was associated with differential CHD event reduction by pravastatin therapy in all 3 studies: P = 0.002 in CARE, P = 0.01 in WOSCOPS, P = 0.002 in PROSPER/PHASE. In a combined analysis of CARE, WOSCOPS, and PROSPER/PHASE, the hazard ratio for CHD when comparing pravastatin with placebo decreased by a factor of 0.63 (95% CI: 0.52 to 0.75) for each extra copy of the minor allele (P = 4.8 * 10(-7)). This SNP is located in DnaJ homolog subfamily C member 5B (DNAJC5B) and merits investigation in additional randomized studies of pravastatin and other statins. PMID- 22666497 TI - Strong neutral spatial effects shape tree species distributions across life stages at multiple scales. AB - Traditionally, ecologists use lattice (regional summary) count data to simulate tree species distributions to explore species coexistence. However, no previous study has explicitly compared the difference between using lattice count and basal area data and analyzed species distributions at both individual species and community levels while simultaneously considering the combined scenarios of life stage and scale. In this study, we hypothesized that basal area data are more closely related to environmental variables than are count data because of strong environmental filtering effects. We also address the contribution of niche and the neutral (i.e., solely dependent on distance) factors to species distributions. Specifically, we separately modeled count data and basal area data while considering life stage and scale effects at the two levels with simultaneous autoregressive models and variation partitioning. A principal coordinates of neighbor matrix (PCNM) was used to model neutral spatial effects at the community level. The explained variations of species distribution data did not differ significantly between the two types of data at either the individual species level or the community level, indicating that the two types of data can be used nearly identically to model species distributions. Neutral spatial effects represented by spatial autoregressive parameters and the PCNM eigenfunctions drove species distributions on multiple scales, different life stages and individual species and community levels in this plot. We concluded that strong neutral spatial effects are the principal mechanisms underlying the species distributions and thus shape biodiversity spatial patterns. PMID- 22666498 TI - Shift of graft-versus-host-disease target organ tropism by dietary vitamin A. AB - Gut-homing of donor T cells is causative for the development of intestinal GvHD in recipients of allogeneic hematopoietic stem cell transplantation (HSCT). Expression of the gut-specific homing receptors integrin-alpha4beta7 and chemokine receptor CCR9 on T cells is imprinted in gut-associated lymphoid tissues (GALT) under the influence of the vitamin A metabolite retinoic acid. Here we addressed the role of vitamin A deficiency in HSCT-recipients for donor T cell migration in the course of experimental GvHD. Vitamin A-deficient (VAD) mice were prepared by feeding them a vitamin A-depleted diet. Experiments were performed in a C57BL/6 into BALB/c model of acute GvHD. We found that expression of integrin-alpha4beta7 and CCR9 in GALT was reduced in VAD recipients after HSCT. Competitive in vivo homing assays showed that allogeneic T cells primed in VAD mice did not home as efficiently to the intestine as T cells primed in mice fed with standard diet (STD). The course of GvHD was ameliorated in VAD HSCT recipients and, consequently, their survival was prolonged compared to recipients receiving STD. However, VAD-recipients were not protected and died of clinical GvHD. We found reduced numbers of donor T cells in the intestine but increased cell counts and tissue damage in other organs of VAD-recipients. Furthermore, we observed high IFN-gamma(+)CD4(+) and low FoxP3(+)CD4(+) frequencies of total donor CD4(+) T cells in VAD as compared to STD recipients. Taken together, these results indicate that dietary vitamin A deficiency in HSCT-recipients changed target organ tropism in GvHD but also resulted in fatal inflammation after HSCT. PMID- 22666500 TI - The RuvA homologues from Mycoplasma genitalium and Mycoplasma pneumoniae exhibit unique functional characteristics. AB - The DNA recombination and repair machineries of Mycoplasma genitalium and Mycoplasma pneumoniae differ considerably from those of gram-positive and gram negative bacteria. Most notably, M. pneumoniae is unable to express a functional RecU Holliday junction (HJ) resolvase. In addition, the RuvB homologues from both M. pneumoniae and M. genitalium only exhibit DNA helicase activity but not HJ branch migration activity in vitro. To identify a putative role of the RuvA homologues of these mycoplasmas in DNA recombination, both proteins (RuvA(Mpn) and RuvA(Mge), respectively) were studied for their ability to bind DNA and to interact with RuvB and RecU. In spite of a high level of sequence conservation between RuvA(Mpn) and RuvA(Mge) (68.8% identity), substantial differences were found between these proteins in their activities. First, RuvA(Mge) was found to preferentially bind to HJs, whereas RuvA(Mpn) displayed similar affinities for both HJs and single-stranded DNA. Second, while RuvA(Mpn) is able to form two distinct complexes with HJs, RuvA(Mge) only produced a single HJ complex. Third, RuvA(Mge) stimulated the DNA helicase and ATPase activities of RuvB(Mge), whereas RuvA(Mpn) did not augment RuvB activity. Finally, while both RuvA(Mge) and RecU(Mge) efficiently bind to HJs, they did not compete with each other for HJ binding, but formed stable complexes with HJs over a wide protein concentration range. This interaction, however, resulted in inhibition of the HJ resolution activity of RecU(Mge). PMID- 22666499 TI - Molecular characterization of podoviral bacteriophages virulent for Clostridium perfringens and their comparison with members of the Picovirinae. AB - Clostridium perfringens is a Gram-positive, spore-forming anaerobic bacterium responsible for human food-borne disease as well as non-food-borne human, animal and poultry diseases. Because bacteriophages or their gene products could be applied to control bacterial diseases in a species-specific manner, they are potential important alternatives to antibiotics. Consequently, poultry intestinal material, soil, sewage and poultry processing drainage water were screened for virulent bacteriophages that lysed C. perfringens. Two bacteriophages, designated PhiCPV4 and PhiZP2, were isolated in the Moscow Region of the Russian Federation while another closely related virus, named PhiCP7R, was isolated in the southeastern USA. The viruses were identified as members of the order Caudovirales in the family Podoviridae with short, non-contractile tails of the C1 morphotype. The genomes of the three bacteriophages were 17.972, 18.078 and 18.397 kbp respectively; encoding twenty-six to twenty-eight ORF's with inverted terminal repeats and an average GC content of 34.6%. Structural proteins identified by mass spectrometry in the purified PhiCP7R virion included a pre neck/appendage with putative lyase activity, major head, tail, connector/upper collar, lower collar and a structural protein with putative lysozyme-peptidase activity. All three podoviral bacteriophage genomes encoded a predicted N acetylmuramoyl-L-alanine amidase and a putative stage V sporulation protein. Each putative amidase contained a predicted bacterial SH3 domain at the C-terminal end of the protein, presumably involved with binding the C. perfringens cell wall. The predicted DNA polymerase type B protein sequences were closely related to other members of the Podoviridae including Bacillus phage Phi29. Whole-genome comparisons supported this relationship, but also indicated that the Russian and USA viruses may be unique members of the sub-family Picovirinae. PMID- 22666501 TI - Immunogenicity of a promiscuous T cell epitope peptide based conjugate vaccine against benzo[a]pyrene: redirecting antibodies to the hapten. AB - The prototype polycyclic aromatic hydrocarbon benzo[a]pyrene (B[a]P) is an environmental pollutant and food contaminant of epidemiological importance. To protect against adverse effects of this ubiquitous carcinogen, we developed an immunoprophylactic strategy based on a B[a]P-protein conjugate vaccine to induce B[a]P specific antibodies (Grova et al., Vaccine. 2009;27:4142-51). Here, we investigated in mice the efficacy of B[a]P-peptide conjugates based on promiscuous T cell epitopes (TCE) into further improve this approach. We showed that B[a]P-peptide conjugates induced very different levels of hapten-specific antibodies with variable functional efficacy, depending on the carrier. In some cases peptide carriers induced a more efficient antibody response against B[a]P than tetanus toxoid as a protein carrier, with the capacity to sequester more B[a]P in the blood. Reducing the carrier size to a single TCE can dramatically shift the antibody bias from the carrier to the B[a]P. Conjugates based on the TCE FIGITEL induced the best anti-hapten response and no antibodies against the carrier peptide. Some peptide conjugates increased the selectivity of the antibodies for the activated metabolite 7,8-diol-B[a]P and B[a]P by one or two orders of magnitude. The antibody efficacy was also demonstrated in their ability to sequester B[a]P in the blood and modulate its faecal excretion (15-56%). We further showed that pre-existing immunity to the carrier from which the TCE was derived did not reduce the immunogenicity of the peptide conjugate. In conclusion, we showed that a vaccination against B[a]P using promiscuous TCEs of tetanus toxin as carriers is feasible even in case of a pre-existing immunity to the toxoid and that some TCE epitopes dramatically redirect the antibody response to the hapten. Further studies to demonstrate a long-term protection of an immunoprophylactic immunisation against B[a]P are warranted. PMID- 22666502 TI - Mesenchymal cell interaction with ovarian cancer cells triggers pro-metastatic properties. AB - Tumor microenvironment is an important actor of ovarian cancer progression but the relations between mesenchymal cells and ovarian cancer cells remain unclear. The objective of this study was to determine the ovarian cancer cells' biological modifications induced by mesenchymal cells. To address this issue, we used two different ovarian cancer cell lines (NIH:OVCAR3 and SKOV3) and co-cultured them with mesenchymal cells. Upon co-culture the different cell populations were sorted to study their transcriptome and biological properties. Transcriptomic analysis revealed three biological-function gene clusters were enriched upon contact with mesenchymal cells. These were related to the increase of metastatic abilities (adhesion, migration and invasion), proliferation and chemoresistance in vitro. Therefore, contact with the mesenchymal cell niche could increase metastatic initiation and expansion through modification of cancer cells. Taken together these findings suggest that pathways involved in hetero-cellular interaction may be targeted to disrupt the acquired pro-metastatic profile. PMID- 22666503 TI - BRCA2 mutations and triple-negative breast cancer. AB - Recently, BRCA1 germline mutations were found in a high proportion (14-34%) of patients with triple-negative breast cancer (TNBC). BRCA2 was either not analyzed or showed much lower mutation frequencies. Therefore, we screened a group of TNBC patients (n = 30) of white European descent for mutations in BRCA2 as well as in BRCA1. Cases were unselected for age of disease-onset (median age at breast cancer diagnosis was 58 years, ranging from 37 to 74 years), family history of cancer and BRCA1 and BRCA2 mutation status. Half of the patients (15/30) showed a family history of breast and/or ovarian cancer. A high frequency of deleterious germline mutations was observed in BRCA2 (5/30; 16.7%), and only one case showed a BRCA1 mutation (3.3%). Although the study group was small, these results point to BRCA2 mutations being important in TNBC. PMID- 22666504 TI - Chagas disease: "the new HIV/AIDS of the Americas". PMID- 22666505 TI - Neurocysticercosis: neglected but not forgotten. PMID- 22666506 TI - Human African trypanosomiasis in South Sudan: how can we prevent a new epidemic? AB - Human African trypanosomiasis (HAT) has been a major public health problem in South Sudan for the last century. Recurrent outbreaks with a repetitive pattern of responding-scaling down activities have been observed. Control measures for outbreak response were reduced when the prevalence decreased and/or socio political crisis erupted, leading to a new increase in the number of cases. This paper aims to raise international awareness of the threat of another outbreak of sleeping sickness in South Sudan. It is a review of the available data, interventions over time, and current reports on the status of HAT in South Sudan. Since 2006, control interventions and treatments providing services for sleeping sickness have been reduced. Access to HAT diagnosis and treatment has been considerably diminished. The current status of control activities for HAT in South Sudan could lead to a new outbreak of the disease unless 1) the remaining competent personnel are used to train younger staff to resume surveillance and treatment in the centers where HAT activities have stopped, and 2) control of HAT continues to be given priority even when the number of cases has been substantially reduced. Failure to implement an effective and sustainable system for HAT control and surveillance will increase the risk of a new epidemic. That would cause considerable suffering for the affected population and would be an impediment to the socioeconomic development of South Sudan. PMID- 22666507 TI - A poor-quality generic drug for the treatment of visceral leishmaniasis: a case report and appeal. PMID- 22666508 TI - More efficient ways of assessing treatments for neglected tropical diseases are required: innovative study designs, new endpoints, and markers of effects. PMID- 22666509 TI - Use of oxfendazole to control porcine cysticercosis in a high-endemic area of Mozambique. AB - A randomized controlled field trial to evaluate the effectiveness of a single oral dose of 30 mg/kg of oxfendazole (OFZ) treatment for control of porcine cysticercosis was conducted in 4 rural villages of Angonia district, north western Mozambique. Two hundred and sixteen piglets aged 4 months were selected and assigned randomly to OFZ treatment or control groups. Fifty-four piglets were treated at 4 months of age (T1), while another 54 piglets were treated at 9 months of age (T2) and these were matched with 108 control pigs from the same litters and raised under the same conditions. Baseline data were collected on the prevalence of porcine cysticercosis using antigen ELISA (Ag-ELISA), as well as knowledge and practices related to Taenia solium transmission based on questionnaire interviews and observations. All animals were followed and re tested for porcine cysticercosis by Ag-ELISA at 9 and 12 months of age when the study was terminated. Overall prevalence at baseline was 5.1% with no significant difference between groups. At the end of the study, 66.7% of the controls were found positive, whereas 21.4% of the T1 and 9.1% of the T2 pigs were positive, respectively. Incidence rates of porcine cysticercosis were lower in treated pigs as compared to controls. Necropsy of 30 randomly selected animals revealed that viable cysts were present in none (0/8) of T2 pigs, 12.5% (1/8) of T1 pigs and 42.8% (6/14) of control pigs. There was a significant reduction in the risk of T. solium cysticercosis if pigs were treated with OFZ either at 4 months (OR = 0.14; 95% CI: 0.05-0.36) or at 9 months of age (OR = 0.05; 95% CI: 0.02-0.16). Strategic treatment of pigs in endemic areas should be further explored as a means to control T. solium cysticercosis/taeniosis. PMID- 22666510 TI - Regulatory T cells in human lymphatic filariasis: stronger functional activity in microfilaremics. AB - Infection with filarial parasites is associated with T cell hyporesponsiveness, which is thought to be partly mediated by their ability to induce regulatory T cells (Tregs) during human infections. This study investigates the functional capacity of Tregs from different groups of filarial patients to suppress filaria specific immune responses during human filariasis. Microfilaremic (MF), chronic pathology (CP) and uninfected endemic normal (EN) individuals were selected in an area endemic for Brugia timori in Flores island, Indonesia. PBMC were isolated, CD4CD25(hi) cells were magnetically depleted and in vitro cytokine production and proliferation in response to B. malayi adult worm antigen (BmA) were determined in total and Treg-depleted PBMC. In MF subjects BmA-specific T and B lymphocyte proliferation as well as IFN-gamma, IL-13 and IL-17 responses were lower compared to EN and CP groups. Depletion of Tregs restored T cell as well as B cell proliferation in MF-positives, while proliferative responses in the other groups were not enhanced. BmA-induced IL-13 production was increased after Treg removal in MF-positives only. Thus, filaria-associated Tregs were demonstrated to be functional in suppressing proliferation and possibly Th2 cytokine responses to BmA. These suppressive effects were only observed in the MF group and not in EN or CP. These findings may be important when considering strategies for filarial treatment and the targeted prevention of filaria-induced lymphedema. PMID- 22666511 TI - Optimizing the colour and fabric of targets for the control of the tsetse fly Glossina fuscipes fuscipes. AB - BACKGROUND: Most cases of human African trypanosomiasis (HAT) start with a bite from one of the subspecies of Glossina fuscipes. Tsetse use a range of olfactory and visual stimuli to locate their hosts and this response can be exploited to lure tsetse to insecticide-treated targets thereby reducing transmission. To provide a rational basis for cost-effective designs of target, we undertook studies to identify the optimal target colour. METHODOLOGY/PRINCIPAL FINDINGS: On the Chamaunga islands of Lake Victoria , Kenya, studies were made of the numbers of G. fuscipes fuscipes attracted to targets consisting of a panel (25 cm square) of various coloured fabrics flanked by a panel (also 25 cm square) of fine black netting. Both panels were covered with an electrocuting grid to catch tsetse as they contacted the target. The reflectances of the 37 different-coloured cloth panels utilised in the study were measured spectrophotometrically. Catch was positively correlated with percentage reflectance at the blue (460 nm) wavelength and negatively correlated with reflectance at UV (360 nm) and green (520 nm) wavelengths. The best target was subjectively blue, with percentage reflectances of 3%, 29%, and 20% at 360 nm, 460 nm and 520 nm respectively. The worst target was also, subjectively, blue, but with high reflectances at UV (35% reflectance at 360 nm) wavelengths as well as blue (36% reflectance at 460 nm); the best low UV-reflecting blue caught 3* more tsetse than the high UV-reflecting blue. CONCLUSIONS/SIGNIFICANCE: Insecticide-treated targets to control G. f. fuscipes should be blue with low reflectance in both the UV and green bands of the spectrum. Targets that are subjectively blue will perform poorly if they also reflect UV strongly. The selection of fabrics for targets should be guided by spectral analysis of the cloth across both the spectrum visible to humans and the UV region. PMID- 22666512 TI - A model of DENV-3 infection that recapitulates severe disease and highlights the importance of IFN-gamma in host resistance to infection. AB - There are few animal models of dengue infection, especially in immunocompetent mice. Here, we describe alterations found in adult immunocompetent mice inoculated with an adapted Dengue virus (DENV-3) strain. Infection of mice with the adapted DENV-3 caused inoculum-dependent lethality that was preceded by several hematological and biochemical changes and increased virus dissemination, features consistent with severe disease manifestation in humans. IFN-gamma expression increased after DENV-3 infection of WT mice and this was preceded by increase in expression of IL-12 and IL-18. In DENV-3-inoculated IFN-gamma(-/-) mice, there was enhanced lethality, which was preceded by severe disease manifestation and virus replication. Lack of IFN-gamma production was associated with diminished NO-synthase 2 (NOS2) expression and higher susceptibility of NOS2(-/-) mice to DENV-3 infection. Therefore, mechanisms of protection to DENV-3 infection rely on IFN-gamma-NOS2-NO-dependent control of viral replication and of disease severity, a pathway showed to be relevant for resistance to DENV infection in other experimental and clinical settings. Thus, the model of DENV-3 infection in immunocompetent mice described here represents a significant advance in animal models of severe dengue disease and may provide an important tool to the elucidation of immunopathogenesis of disease and of protective mechanisms associated with infection. PMID- 22666513 TI - Experimental induction of paromomycin resistance in antimony-resistant strains of L. donovani: outcome dependent on in vitro selection protocol. AB - Paromomycin (PMM) has recently been introduced for treatment of visceral leishmaniasis in India. Although no clinical resistance has yet been reported, proactive vigilance should be warranted. The present in vitro study compared the outcome and stability of experimental PMM-resistance induction on promastigotes and intracellular amastigotes. Cloned antimony-resistant L. donovani field isolates from India and Nepal were exposed to stepwise increasing concentrations of PMM (up to 500 uM), either as promastigotes or intracellular amastigotes. One resulting resistant strain was cloned and checked for stability of resistance by drug-free in vitro passage as promastigotes for 20 weeks or a single in vivo passage in the golden hamster. Resistance selection in promastigotes took about 25 weeks to reach the maximal 97 uM inclusion level that did not affect normal growth. Comparison of the IC(50) values between the parent and the selected strains revealed a 9 to 11-fold resistance for the Indian and 3 to 5-fold for the Nepalese strains whereby the resistant phenotype was also maintained at the level of the amastigote. Applying PMM pressure to intracellular amastigotes produced resistance after just two selection cycles (IC(50) = 199 uM) compared to the parent strain (IC(50) = 45 uM). In the amastigote-induced strains/clones, lower PMM susceptibilities were seen only in amastigotes and not at all in promastigotes. This resistance phenotype remained stable after serial in vitro passage as promastigote for 20 weeks and after a single in vivo passage in the hamster. This study clearly demonstrates that a different PMM-resistance phenotype is obtained whether drug selection is applied to promastigotes or intracellular amastigotes. These findings may have important relevance to resistance mechanism investigations and the likelihood of resistance development and detection in the field. PMID- 22666514 TI - The diagnostic accuracy of serologic and molecular methods for detecting visceral leishmaniasis in HIV infected patients: meta-analysis. AB - BACKGROUND: Human visceral leishmaniasis (VL), a potentially fatal disease, has emerged as an important opportunistic condition in HIV infected patients. In immunocompromised patients, serological investigation is considered not an accurate diagnostic method for VL diagnosis and molecular techniques seem especially promising. OBJECTIVE: This work is a comprehensive systematic review and meta-analysis to evaluate the accuracy of serologic and molecular tests for VL diagnosis specifically in HIV-infected patients. METHODS: Two independent reviewers searched PubMed and LILACS databases. The quality of studies was assessed by QUADAS score. Sensitivity and specificity were pooled separately and compared with overall accuracy measures: diagnostic odds ratio (DOR) and symmetric summary receiver operating characteristic (sROC). RESULTS: Thirty three studies recruiting 1,489 patients were included. The following tests were evaluated: Immunofluorescence Antibody Test (IFAT), Enzyme linked immunosorbent assay (ELISA), immunoblotting (Blot), direct agglutination test (DAT) and polimerase chain reaction (PCR) in whole blood and bone marrow. Most studies were carried out in Europe. Serological tests varied widely in performance, but with overall limited sensitivity. IFAT had poor sensitivity ranging from 11% to 82%. DOR (95% confidence interval) was higher for DAT 36.01 (9.95-130.29) and Blot 27.51 (9.27-81.66) than for IFAT 7.43 (3.08-1791) and ELISA 3.06 (0.71-13.10). PCR in whole blood had the highest DOR: 400.35 (58.47-2741.42). The accuracy of PCR based on Q-point was 0.95; 95%CI 0.92-0.97, which means good overall performance. CONCLUSION: Based mainly on evidence gained by infection with Leishmania infantum chagasi, serological tests should not be used to rule out a diagnosis of VL among the HIV-infected, but a positive test at even low titers has diagnostic value when combined with the clinical case definition. Considering the available evidence, tests based on DNA detection are highly sensitive and may contribute to a diagnostic workup. PMID- 22666515 TI - The Sigma class glutathione transferase from the liver fluke Fasciola hepatica. AB - BACKGROUND: Liver fluke infection of livestock causes economic losses of over US$ 3 billion worldwide per annum. The disease is increasing in livestock worldwide and is a re-emerging human disease. There are currently no commercial vaccines, and only one drug with significant efficacy against adult worms and juveniles. A liver fluke vaccine is deemed essential as short-lived chemotherapy, which is prone to resistance, is an unsustainable option in both developed and developing countries. Protein superfamilies have provided a number of leading liver fluke vaccine candidates. A new form of glutathione transferase (GST) family, Sigma class GST, closely related to a leading Schistosome vaccine candidate (Sm28), has previously been revealed by proteomics in the liver fluke but not functionally characterised. METHODOLOGY/PRINCIPAL FINDINGS: In this manuscript we show that a purified recombinant form of the F. hepatica Sigma class GST possesses prostaglandin synthase activity and influences activity of host immune cells. Immunocytochemistry and western blotting have shown the protein is present near the surface of the fluke and expressed in eggs and newly excysted juveniles, and present in the excretory/secretory fraction of adults. We have assessed the potential to use F. hepatica Sigma class GST as a vaccine in a goat-based vaccine trial. No significant reduction of worm burden was found but we show significant reduction in the pathology normally associated with liver fluke infection. CONCLUSIONS/SIGNIFICANCE: We have shown that F. hepatica Sigma class GST has likely multi-functional roles in the host-parasite interaction from general detoxification and bile acid sequestration to PGD synthase activity. PMID- 22666516 TI - Leptospirosis in American Samoa--estimating and mapping risk using environmental data. AB - BACKGROUND: The recent emergence of leptospirosis has been linked to many environmental drivers of disease transmission. Accurate epidemiological data are lacking because of under-diagnosis, poor laboratory capacity, and inadequate surveillance. Predictive risk maps have been produced for many diseases to identify high-risk areas for infection and guide allocation of public health resources, and are particularly useful where disease surveillance is poor. To date, no predictive risk maps have been produced for leptospirosis. The objectives of this study were to estimate leptospirosis seroprevalence at geographic locations based on environmental factors, produce a predictive disease risk map for American Samoa, and assess the accuracy of the maps in predicting infection risk. METHODOLOGY AND PRINCIPAL FINDINGS: Data on seroprevalence and risk factors were obtained from a recent study of leptospirosis in American Samoa. Data on environmental variables were obtained from local sources, and included rainfall, altitude, vegetation, soil type, and location of backyard piggeries. Multivariable logistic regression was performed to investigate associations between seropositivity and risk factors. Using the multivariable models, seroprevalence at geographic locations was predicted based on environmental variables. Goodness of fit of models was measured using area under the curve of the receiver operating characteristic, and the percentage of cases correctly classified as seropositive. Environmental predictors of seroprevalence included living below median altitude of a village, in agricultural areas, on clay soil, and higher density of piggeries above the house. Models had acceptable goodness of fit, and correctly classified ~84% of cases. CONCLUSIONS AND SIGNIFICANCE: Environmental variables could be used to identify high-risk areas for leptospirosis. Environmental monitoring could potentially be a valuable strategy for leptospirosis control, and allow us to move from disease surveillance to environmental health hazard surveillance as a more cost-effective tool for directing public health interventions. PMID- 22666517 TI - Changes of myogenic reactive oxygen species and interleukin-6 in contracting skeletal muscle cells. AB - The aim of this study was to measure changes in myotube reactive oxygen species (ROS) and the production of interleukin (IL)-6 in electrically stimulated mouse C2C12 skeletal muscle cells. After five days of differentiation, myotubes were stimulated using an electrical stimulator set at 45 V at a frequency of 5 Hz, with a pulse width of 20 ms. Acute stimulations were performed for 45, 60, 75, 90, or 120 min in each dish. ROSs were detected in the extracted cells directly using a fluorescent probe. IL-6 mRNA expression in C2C12 myotubes and IL-6 concentration in C2C12 myotube supernatants were determined using real-time PCR and ELISA, respectively. Compared with control cells, ROS generation was significantly increased at 45 min after the onset of stimulation (P < 0.01) and continued to increase, reaching a maximum at 120 min. IL-6 mRNA expression and IL 6 concentration in C2C12 cells were significantly increased after 75 min (P < 0.01) and 120 min (P < 0.05) of electrical stimulation (ES) compared with the control cells. Our data show that a specific ES intensity may modulate ROS accumulation and affect IL-6 gene expression in contracting skeletal muscle cells. PMID- 22666518 TI - Schisandrin B as a hormetic agent for preventing age-related neurodegenerative diseases. AB - Oxidative stress and mitochondrial dysfunction have been implicated in the pathogenesis of neurodegenerative diseases, with the latter preceding the appearance of clinical symptoms. The energy failure resulting from mitochondrial dysfunction further impedes brain function, which demands large amounts of energy. Schisandrin B (Sch B), an active ingredient isolated from Fructus Schisandrae, has been shown to afford generalized tissue protection against oxidative damage in various organs, including the brain, of experimental animals. Recent experimental findings have further demonstrated that Sch B can protect neuronal cells against oxidative challenge, presumably by functioning as a hormetic agent to sustain cellular redox homeostasis and mitoenergetic capacity in neuronal cells. The combined actions of Sch B offer a promising prospect for preventing or possibly delaying the onset of neurodegenerative diseases, as well as enhancing brain health. PMID- 22666519 TI - The human tripeptide GHK-Cu in prevention of oxidative stress and degenerative conditions of aging: implications for cognitive health. AB - Oxidative stress, disrupted copper homeostasis, and neuroinflammation due to overproduction of proinflammatory cytokines are considered leading causative factors in development of age-associated neurodegenerative conditions. Recently, a new mechanism of aging-detrimental epigenetic modifications-has emerged. Thus, compounds that possess antioxidant, anti-inflammatory activity as well as compounds capable of restoring copper balance and proper gene functioning may be able to prevent age-associated cognitive decline and ward off many common neurodegenerative conditions. The aim of this paper is to bring attention to a compound with a long history of safe use in wound healing and antiaging skin care. The human tripeptide GHK was discovered in 1973 as an activity in human albumin that caused old human liver tissue to synthesize proteins like younger tissue. It has high affinity for copper ions and easily forms a copper complex or GHK-Cu. In addition, GHK possesses a plethora of other regenerative and protective actions including antioxidant, anti-inflammatory, and wound healing properties. Recent studies revealed its ability to up- and downregulate a large number of human genes including those that are critical for neuronal development and maintenance. We propose GHK tripeptide as a possible therapeutic agent against age-associated neurodegeneration and cognitive decline. PMID- 22666520 TI - Metformin rescues the myocardium from doxorubicin-induced energy starvation and mitochondrial damage in rats. AB - Clinical use of doxorubicin (DOX) is limited by its cardiotoxic side effects. Recent studies established that metformin (MET), an oral antidiabetic drug, possesses an antioxidant activity. However, whether it can protect against DOX induced energy starvation and mitochondrial damage has not been reported. Our results, in a rat model of DOX-induced cardiotoxicity, show that DOX treatment significantly increased serum levels of LDH and CK-MB, indicators of cardiac injury, and induced expression of hypertrophic gene markers. DOX also caused marked decreases in the cardiac levels of glutathione, CoA-SH and ATP, and mRNA expression of catalase and NQO-1. These biochemical changes were associated with myocardial histopathological and ultrastructural deteriorations, as observed by light and electron microscopy, respectively. Cotreatment with MET (500 mg/kg) eliminated all DOX-induced biochemical, histopathological, and ultrastructural changes. These findings demonstrate that MET successfully prevents DOX-induced cardiotoxicity in vivo by inhibiting DOX-induced oxidative stress, energy starvation, and depletion of intramitochondrial CoA-SH. PMID- 22666521 TI - Accumulation of exogenous amyloid-beta peptide in hippocampal mitochondria causes their dysfunction: a protective role for melatonin. AB - Amyloid-beta (Abeta) pathology is related to mitochondrial dysfunction accompanied by energy reduction and an elevated production of reactive oxygen species (ROS). Monomers and oligomers of Abeta have been found inside mitochondria where they accumulate in a time-dependent manner as demonstrated in transgenic mice and in Alzheimer's disease (AD) brain. We hypothesize that the internalization of extracellular Abeta aggregates is the major cause of mitochondrial damage and here we report that following the injection of fibrillar Abeta into the hippocampus, there is severe axonal damage which is accompanied by the entrance of Abeta into the cell. Thereafter, Abeta appears in mitochondria where it is linked to alterations in the ionic gradient across the inner mitochondrial membrane. This effect is accompanied by disruption of subcellular structure, oxidative stress, and a significant reduction in both the respiratory control ratio and in the hydrolytic activity of ATPase. Orally administrated melatonin reduced oxidative stress, improved the mitochondrial respiratory control ratio, and ameliorated the energy imbalance. PMID- 22666522 TI - Tirapazamine-doxorubicin interaction referring to heart oxidative stress and Ca2+ balance protein levels. AB - Doxorubicin (DOX) causes long-term cardiomyopathy that is dependent on oxidative stress and contractility disorders. Tirapazamine (TP), an experimental adjuvant drug, passes the same red-ox transformation as DOX. The aim of the study was to evaluate an effect of tirapazamine on oxidative stress, contractile protein level, and cardiomyocyte necrosis in rats administered doxorubicin. Rats were intraperitoneally injected six times once a week with tirapazamine in two doses, 5 (5TP) and 10 mg/kg (10TP), while doxorubicin was administered in dose 1.8 mg/kg (DOX). Subsequent two groups received both drugs simultaneously (5TP+DOX and 10TP+DOX). Tirapazamine reduced heart lipid peroxidation and normalised RyR2 protein level altered by doxorubicin. There were no significant changes in GSH/GSSG ratio, total glutathione, cTnI, AST, and SERCA2 level between DOX and TP+DOX groups. Cardiomyocyte necrosis was observed in groups 10TP and 10TP+DOX. PMID- 22666525 TI - Lymphoepithelial carcinoma of the parotid gland: a rare neck lump. PMID- 22666524 TI - Global hypomethylation in hepatocellular carcinoma and its relationship to aflatoxin B(1) exposure. AB - AIM: To determine global DNA methylation in paired hepatocellular carcinoma (HCC) samples using several different assays and explore the correlations between hypomethylation and clinical parameters and biomarkers, including that of aflatoxin B(1) exposure. METHODS: Using the radio labeled methyl acceptance assay as a measure of global hypomethylation, as well as two repetitive elements, including satellite 2 (Sat2) by MethyLight and long interspersed nucleotide elements (LINE1), by pyrosequencing. RESULTS: By all three assays, mean methylation levels in tumor tissues were significantly lower than that in adjacent tissues. Methyl acceptance assay log (mean +/- SD) disintegrations/min/ng DNA are 70.0 +/- 54.8 and 32.4 +/- 15.6, respectively, P = 0.040; percent methylation of Sat2 42.2 +/- 55.1 and 117.9 +/- 88.8, respectively, P < 0.0001 and percent methylation LINE1 48.6 +/- 14.8 and 71.7 +/- 1.4, respectively, P < 0.0001. Aflatoxin B(1)-albumin (AFB(1)-Alb) adducts, a measure of exposure to this dietary carcinogen, were inversely correlated with LINE1 methylation (r = -0.36, P = 0.034). CONCLUSION: Consistent hypomethylation in tumor compared to adjacent tissue was found by the three different methods. AFB(1) exposure is associated with DNA global hypomethylation, suggesting that chemical carcinogens may influence epigenetic changes in humans. PMID- 22666523 TI - Anticancer activity of green tea polyphenols in prostate gland. AB - Numerous evidences from prevention studies in humans, support the existence of an association between green tea polyphenols consumption and a reduced cancer risk. Prostate cancer is one of the most frequently diagnosed male neoplasia in the Western countries, which is in agreement with this gland being particularly vulnerable to oxidative stress processes, often associated with tumorigenesis. Tea polyphenols have been extensively studied in cell culture and animal models where they inhibited tumor onset and progression. Prostate cancer appears a suitable target for primary prevention care, since it grows slowly, before symptoms arise, thus offering a relatively long time period for therapeutic interventions. It is, in fact, usually diagnosed in men 50-year-old or older, when even a modest delay in progression of the disease could significantly improve the patients quality of life. Although epidemiological studies have not yet yielded conclusive results on the chemopreventive and anticancer effect of tea polyphenols, there is an increasing trend to employ these substances as conservative management for patients diagnosed with less advanced prostate cancer. Here, we intend to review the most recent observations relating tea polyphenols to human prostate cancer risk, in an attempt to outline better their potential employment for preventing prostate cancer. PMID- 22666526 TI - Rare presentation of primary coloduodenal fistula. PMID- 22666527 TI - Presentation skills amongst surgical trainees at a national conference: an observational study. AB - OBJECTIVES: The ability to deliver public presentations is important for doctors of all specialities. Despite this, there is little emphasis on training in presentation skills within medical curriculae. The aim of this paper was to establish the current standard of presentations being delivered by surgical trainees at a national conference and to confirm the need for further training. DESIGN: An observational study of 96 six-minute research presentations. SETTING: A national surgical conference in the United Kingdom. PARTICIPANTS: Four independent observers each appraised 24 six-minute presentations by surgical trainees against a pre-determined standard. MAIN OUTCOME MEASURES: A set of 19 audit criteria were established after a literature search to ascertain commonly accepted presentation standards. These outcome measures included keeping to time, number of slides used, the nature of slide content, methods of data representation, use of images and presentation style. RESULTS: A total of 61 (64%) presenters overran. The median number of slides used was 13 (range 6-28). Thirty-three (34%) presenters displayed slides with more than six bullet points on two or more occasions. Sixty-four (67%) presenters displayed whole paragraphs of text on two or more occasions. Sixty-eight (71%) presenters displayed raw numerical data in the course of their presentations. Seventy (73%) presenters used images. Thirty-one (32%) presenters repeatedly read out sentences word-for word from their slides. Nineteen (20%) presenters appeared not to know their presentation content well. CONCLUSIONS: Presentation skills amongst surgical trainees are well below those that should be aspired to. Efforts to improve training, motivation and the examples set by senior surgeons should be instigated in order to improve this situation. PMID- 22666528 TI - Hyperpigmented Paget's disease of the nipple - a diagnostic dilemma. PMID- 22666529 TI - Comparison of chronic fatigue syndrome/myalgic encephalopathy with other disorders: an observational study. AB - OBJECTIVES: To examine the level of activity in online discussion forums for chronic fatigue syndrome/myalgic encephalopathy (CFS/ME) compared to other disorders. We hypothesized the level of activity to be higher in CFS/ME online discussion forums. DESIGN: Observational study SETTING: Norway, which has more than 80% household coverage in internet access, September 2009 PARTICIPANTS: Twelve Norwegian disorder-related online discussion forums MAIN OUTCOME MEASURES: Number of registered users and number of posted messages on each discussion forum RESULTS: Two forums were targeted towards individuals with CFS/ME. These forums had the highest number of registered users per estimated 1,000 cases in the population (50.5 per 1,000 and 29.7 per 1,000), followed by a site for drug dependency (5.4 per 1,000). Counting the number of posted messages per 1,000 cases gave similar indications of high online activity in the CFS/ME discussion forums. CONCLUSIONS: CFS/ME online forums had more than ten times the relative activity of any other disorder or condition related forum. This high level of activity may have multiple explanations. Individuals suffering from a stigmatized condition of unknown aetiology may use the internet to look for explanations of symptoms or to seek out alternative treatments. Internet forum activity may also be reinforced by the creation of in-group identity and pre-morbid personality traits. More knowledge on the type and quality of information provided in online forums is urgently needed. PMID- 22666530 TI - The constructive use of images in medical teaching: a literature review. AB - This literature review illustrates the various ways images are used in teaching and the evidence appertaining to it and advice regarding permissions and use. Four databases were searched, 23 papers were retained out of 135 abstracts found for the study. Images are frequently used to motivate an audience to listen to a lecture or to note key medical findings. Images can promote observation skills when linked with learning outcomes, but the timing and relevance of the images is important - it appears they must be congruent with the dialogue. Student reflection can be encouraged by asking students to actually draw their own impressions of a course as an integral part of course feedback. Careful structured use of images improve attention, cognition, reflection and possibly memory retention. PMID- 22666531 TI - Embedding online patient record access in UK primary care: a survey of stakeholder experiences. AB - OBJECTIVES: To explore the integration of online patient Record Access within UK Primary Care, its perceived impacts on workload and service quality, and barriers to implementation. DESIGN: Mixed format survey of clinicians, administrators and patients. Telephone interviews with non-users. SETTING: Primary care centres within NHS England that had offered online record access for the preceding year. PARTICIPANTS: Of the 57 practices initially agreeing to pilot the system, 32 had adopted it and 16 of these returned questionnaires. The 42 individual respondents included 14 practice managers, 15 clinicians and 13 patients. Follow-up interviews were conducted with one participant from 15 of the 25 non-adopter practices. RESULTS: Most professionals believed that the system is easy to integrate within primary care; while most patients found it easy to integrate within their daily lives. Professionals perceived no increase in the volume of patient queries or clinical consultations as a result of Record Access; indeed some believed that these had decreased. Most clinicians and patients believed that the service had improved mutual trust, communication, patients' health knowledge and health behaviour. Inhibiting factors included concerns about security, liability and resource requirements. Non-adoption was most frequently attributed to competing priorities, rather than negative beliefs about the service. CONCLUSIONS: Record access has an important role to play in supporting patient-focused healthcare policies in the UK and may be easily accommodated within existing services. Additional materials to facilitate patient recruitment, inform system set-up processes, and assure clinicians of their legal position are likely to encourage more widespread adoption. PMID- 22666532 TI - Patient information leaflets for extracorporeal shock wave lithotripsy: questionnaire survey. AB - OBJECTIVES: To compare the level of information provided in extracorporeal shock wave lithotripsy (ESWL) patient information leaflets in the London and East of England Deaneries DESIGN: All trusts in the London and East of England Deanery who offer an ESWL service were contacted and leaflets were compared SETTING: London and East of England Deanery PARTICIPANTS: Alan Askari, Iqbal Shergill MAIN OUTCOME MEASURES: Examination of key information that was communicated to ESWL patients via leaflets RESULTS: 12 trusts responded across the two deaneries. There was significant variation in the amount of information provided in the leaflets with some leaflets not containing an adequate level of instruction or information to patients CONCLUSIONS: The authors propose that a national standardised information leaflet should be incorporated with the British Association of Urological Surgeons (BAUS) procedure specific information leaflet for ESWL procedures. PMID- 22666533 TI - TGR5 potentiates GLP-1 secretion in response to anionic exchange resins. AB - Anionic exchange resins are bona fide cholesterol-lowering agents with glycemia lowering actions in diabetic patients. Potentiation of intestinal GLP-1 secretion has been proposed to contribute to the glycemia lowering effect of these non systemic drugs. Here, we show that resin exposure enhances GLP-1 secretion and improves glycemic control in diet-induced animal models of "diabesity", effects which are critically dependent on TGR5, a G protein-coupled receptor that is activated by bile acids. We identified the colon as a major source of GLP-1 secretion after resin treatment. Furthermore, we demonstrate that the boost in GLP-1 release by resins is due to both enhanced TGR5-dependent production of the precursor transcript of GLP-1 as well as to the local enrichment of TGR5 agonists in the colon. Thus, TGR5 represents an essential component in the pathway mediating the enhanced GLP-1 release in response to anionic exchange resins. PMID- 22666534 TI - High-fat diet transition reduces brain DHA levels associated with altered brain plasticity and behaviour. AB - To assess how the shift from a healthy diet rich in omega-3 fatty acids to a diet rich in saturated fatty acid affects the substrates for brain plasticity and function, we used pregnant rats fed with omega-3 supplemented diet from their 2nd day of gestation period as well as their male pups for 12 weeks. Afterwards, the animals were randomly assigned to either a group fed on the same diet or a group fed on a high-fat diet (HFD) rich in saturated fats for 3 weeks. We found that the HFD increased vulnerability for anxiety-like behavior, and that these modifications harmonized with changes in the anxiety-related NPY1 receptor and the reduced levels of BDNF, and its signalling receptor pTrkB, as well as the CREB protein. Brain DHA contents were significantly associated with the levels of anxiety-like behavior in these rats. PMID- 22666535 TI - Controllable effects of quantum fluctuations on spin free-induction decay at room temperature. AB - Fluctuations of local fields cause decoherence of quantum objects. Usually at high temperatures, thermal noises are much stronger than quantum fluctuations unless the thermal effects are suppressed by certain techniques such as spin echo. Here we report the discovery of strong quantum-fluctuation effects of nuclear spin baths on free-induction decay of single electron spins in solids at room temperature. We find that the competition between the quantum and thermal fluctuations is controllable by an external magnetic field. These findings are based on Ramsey interference measurement of single nitrogen-vacancy center spins in diamond and numerical simulation of the decoherence, which are in excellent agreement. PMID- 22666536 TI - Comparative genomics of the Hedgehog loci in chordates and the origins of Shh regulatory novelties. AB - The origin and evolution of the complex regulatory landscapes of some vertebrate developmental genes, often spanning hundreds of Kbp and including neighboring genes, remain poorly understood. The Sonic Hedgehog (Shh) genomic regulatory block (GRB) is one of the best functionally characterized examples, with several discrete enhancers reported within its introns, vast upstream gene-free region and neighboring genes (Lmbr1 and Rnf32). To investigate the origin and evolution of this GRB, we sequenced and characterized the Hedgehog (Hh) loci from three invertebrate chordate amphioxus species, which share several early expression domains with Shh. Using phylogenetic footprinting within and between chordate lineages, and reporter assays in zebrafish probing >30 Kbp of amphioxus Hh, we report large sequence and functional divergence between both groups. In addition, we show that the linkage of Shh to Lmbr1 and Rnf32, necessary for the unique gnatostomate-specific Shh limb expression, is a vertebrate novelty occurred between the two whole-genome duplications. PMID- 22666537 TI - EMT and induction of miR-21 mediate metastasis development in Trp53-deficient tumours. AB - Missense mutations in TP53 gene promote metastasis in human tumours. However, little is known about the complete loss of function of p53 in tumour metastasis. Here we show that squamous cell carcinomas generated by the specific ablation of Trp53 gene in mouse epidermis are highly metastatic. Biochemical and genome-wide mRNA and miRNA analyses demonstrated that metastases are associated with the early induction of epithelial-mesenchymal transition (EMT) and deregulated miRNA expression in primary tumours. Increased expression of miR-21 was observed in undifferentiated, prometastatic mouse tumours and in human tumours characterized by p53 mutations and distant metastasis. The augmented expression of miR-21, mediated by active mTOR and Stat3 signalling, conferred increased invasive properties to mouse keratinocytes in vitro and in vivo, whereas blockade of miR 21 in a metastatic spindle cell line inhibits metastasis development. Collectively these data identify novel molecular mechanisms leading to metastasis in vivo originated by p53 loss in epithelia. PMID- 22666538 TI - Correlative light and scanning X-ray scattering microscopy of healthy and pathologic human bone sections. AB - Scanning small and wide angle X-ray scattering (scanning SWAXS) experiments were performed on healthy and pathologic human bone sections. Via crystallographic tools the data were transformed into quantitative images and as such compared with circularly polarized light (CPL) microscopy images. SWAXS and CPL images allowed extracting information of the mineral nanocrystalline phase embedded, with and without preferred orientation, in the collagen fibrils, mapping local changes at sub-osteon resolution. This favorable combination has been applied for the first time to biopsies of dwarfism syndrome and Paget's disease to shed light onto the cortical structure of natural bone in healthy and pathologic sections. PMID- 22666539 TI - Explicit hypoxia targeting with tumor suppression by creating an "obligate" anaerobic Salmonella Typhimurium strain. AB - Using bacteria as therapeutic agents against solid tumors is emerging as an area of great potential in the treatment of cancer. Obligate and facultative anaerobic bacteria have been shown to infiltrate the hypoxic regions of solid tumors, thereby reducing their growth rate or causing regression. However, a major challenge for bacterial therapy of cancer with facultative anaerobes is avoiding damage to normal tissues. Consequently the virulence of bacteria must be adequately attenuated for therapeutic use. By placing an essential gene under a hypoxia conditioned promoter, SalmonellaTyphimurium strain SL7207 was engineered to survive only in anaerobic conditions (strain YB1) without otherwise affecting its functions. In breast tumor bearing nude mice, YB1 grew within the tumor, retarding its growth, while being rapidly eliminated from normal tissues. YB1 provides a safe bacterial vector for anti-tumor therapies without compromising the other functions or tumor fitness of the bacterium as attenuation methods normally do. PMID- 22666540 TI - Noiseonomics: the relationship between ambient noise levels in the sea and global economic trends. AB - In recent years, the topic of noise in the sea and its effects on marine mammals has attracted considerable attention from both the scientific community and the general public. Since marine mammals rely heavily on acoustics as a primary means of communicating, navigating, and foraging in the ocean, any change in their acoustic environment may have an impact on their behavior. Specifically, a growing body of literature suggests that low-frequency, ambient noise levels in the open ocean increased approximately 3.3 dB per decade during the period 1950 2007. Here we show that this increase can be attributed primarily to commercial shipping activity, which in turn, can be linked to global economic growth. As a corollary, we conclude that ambient noise levels can be directly related to global economic conditions. We provide experimental evidence supporting this theory and discuss its implications for predicting future noise levels based on global economic trends. PMID- 22666541 TI - Abrogated cryptic activation of lentiviral transfer vectors. AB - Despite significant improvements in lentivirus (LV) vector-based gene therapy there are still several safety risks using LV vectors including the potential formation of replication-competent LV particles. To address this shortcoming, we constructed a novel and safer gene transfer system using modified SIN-based LV gene transfer vectors. Central to our approach is a conditional deletion of the Psi packaging signal after integration in the target genome. Here we demonstrate that after transduction of target cells, conventional SIN-based LV transfer vectors can still be mobilized. However mobilization is rendered undetectable if transductions are followed by a Cre/loxP-mediated excision of Psi. Thus conditional elimination of the packaging signal may represent another advance in increasing the safety of LV vectors for gene therapeutic treatment of chronic diseases. PMID- 22666542 TI - Real-time monitoring in three-dimensional hepatocytes reveals that insulin acts as a synchronizer for liver clock. AB - Resetting the peripheral clock and understanding the integration between the circadian rhythm and metabolic pathways are fundamental questions. To test whether insulin acts as a synchronizer for the hepatic clock by cell-autonomous mechanisms, the phase-resetting capabilities of insulin were investigated in cultured hepatic cells. We provide evidence that three-dimensional (3D) cell culture conditions that preserve the differentiated state of primary hepatocytes sustained the robustness of the molecular clock, while this robustness rapidly dampened under classical monolayer cell culture conditions. Herein, we established a 3D cell culture system coupled with a real-time luciferase reporter, and demonstrated that insulin directly regulates the phase entrainment of hepatocyte circadian oscillators. We found that insulin-deficient diabetic rats had a pronounced phase advance in their hepatic clock. Subsequently, a single administration of insulin induced phase-dependent bi-directional phase shifts in diabetic rat livers. Our results clearly demonstrate that insulin is a liver clock synchronizer. PMID- 22666543 TI - Immunological function of sphingosine 1-phosphate in the intestine. AB - It has been shown that dietary materials are involved in immune regulation in the intestine. Lipids mediate immune regulation through a complex metabolic network that produces many kinds of lipid mediators. Sphingosine-1-phosphate (S1P) is a lipid mediator that controls cell trafficking and activation. In this review, we focus on the immunological functions of S1P in the regulation of intestinal immune responses such as immunoglobulin A production and unique T cell trafficking, and its role in the development of intestinal immune diseases such as food allergies and intestinal inflammation, and also discuss the relationship between dietary materials and S1P metabolism. PMID- 22666544 TI - Binge eating and weight-related quality of life in obese adolescents. AB - Limited data exist regarding the association between binge eating and quality of life (QOL) in obese adolescent girls and boys. We, therefore, studied binge eating and QOL in 158 obese (BMI >= 95th percentile) adolescents (14.5 +/- 1.4 years, 68.0% female, 59% African-American) prior to weight-loss treatment. Youth completed an interview to assess binge eating and a questionnaire measure of QOL. Controlling for body composition, binge eating youth (n = 35), overall, reported poorer QOL in domains of health, mobility, and self-esteem compared to those without binge eating (ps < 0.05). Also, girls, overall, reported poorer QOL than boys in activities of daily-living, mobility, self-esteem, and social/interpersonal functioning (ps < 0.05). Girls with binge eating reported the greatest impairments in activities of daily living, mobility, self-esteem, social/interpersonal functioning, and work/school QOL (ps < 0.05). Among treatment-seeking obese adolescents, binge eating appears to be a marker of QOL impairment, especially among girls. Prospective and treatment designs are needed to explore the directional relationship between binge eating and QOL and their impact on weight outcomes. PMID- 22666545 TI - Vitamin D signaling in the bovine immune system: a model for understanding human vitamin D requirements. AB - The endocrine physiology of vitamin D in cattle has been rigorously investigated and has yielded information on vitamin D requirements, endocrine function in health and disease, general metabolism, and maintenance of calcium homeostasis in cattle. These results are relevant to human vitamin D endocrinology. The current debate regarding vitamin D requirements is centered on the requirements for proper intracrine and paracrine vitamin D signaling. Studies in adult and young cattle can provide valuable insight for understanding vitamin D requirements as they relate to innate and adaptive immune responses during infectious disease. In cattle, toll-like receptor recognition activates intracrine and paracrine vitamin D signaling mechanism in the immune system that regulates innate and adaptive immune responses in the presence of adequate 25-hydroxyvitamin D. Furthermore, experiments with mastitis in dairy cattle have provided in vivo evidence for the intracrine vitamin D signaling mechanism in macrophages as well as vitamin D mediated suppression of infection. Epidemiological evidence indicates that circulating concentrations above 32 ng/mL of 25-hydroxyvitamin D are necessary for optimal vitamin D signaling in the immune system, but experimental evidence is lacking for that value. Experiments in cattle can provide that evidence as circulating 25-hydroxyvitamin D concentrations can be experimentally manipulated within ranges that are normal for humans and cattle. Additionally, young and adult cattle can be experimentally infected with bacteria and viruses associated with significant diseases in both cattle and humans. Utilizing the bovine model to further delineate the immunomodulatory role of vitamin D will provide potentially valuable insights into the vitamin D requirements of both humans and cattle, especially as they relate to immune response capacity and infectious disease resistance. PMID- 22666546 TI - Serum 25-hydroxyvitamin D levels among Boston trainee doctors in winter. AB - As indoor workers, trainee doctors may be at risk for inadequate vitamin D. All trainee doctors (residents) in a Boston pediatric training program (residency) were invited to complete a survey, and undergo testing for serum 25 hydroxyvitamin D [25(OH)D], PTH, and calcium during a 3-week period in March 2010. We examined the association between resident characteristics and serum 25(OH)D using Chi2 and Kruskal-Wallis test and multivariable linear and logistic regression. Of the 119 residents, 102 (86%) participated. Although the mean serum 25(OH)D level was 67 nmol/L (+/-26), 25 (25%) had a level <50 nmol/L and 3 (3%) residents had levels <25 nmol/L. In the multivariable model, factors associated with 25(OH)D levels were: female sex (beta 12.7, 95% CI 3.6, 21.7), white race (beta 21.7, 95% CI 11.7, 31.7), travel to more equatorial latitudes during the past 3 months (beta 6.3, 95% CI 2.0, 10.5) and higher daily intake of vitamin D (beta 1.1, 95% CI 0.04, 2.1). Although one in four residents in our study had a serum 25(OH)D <50 nmol/L, all of them would have been missed using current Centers for Medicare and Medicaid Services (CMS) screening guidelines. The use of traditional risk factors appears insufficient to identify low vitamin D in indoor workers at northern latitudes. PMID- 22666549 TI - Alimentary Canal of the Adult Blow Fly, Chrysomya megacephala (F.) (Diptera: Calliphoridae)-Part I: Ultrastructure of Salivary Glands. AB - The salivary gland ultrastructure of the adult male blow fly, Chrysomya megacephala (F.) (Diptera: Calliphoridae), was investigated at the ultrastructural level using light microscopy (LM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The salivary glands are paired structures composed of a single median deferent duct bifurcated into two long, narrow efferent ducts connected to the coiled tubular glands. The SEM image of the gland surface revealed that the basal lamina is relatively smooth in general, but the whole surface appeared as a trace of rough swollen insertion by intense tracheal ramification. Ultrastructurally, the salivary gland is enclosed within the basal lamina, and interdigitation cytoplasmic extensions were apparent between the adjacent gland cells. The basement membrane appeared infoldings that is similar to the complex of the labyrinth channel. The cytoplasm characteristic of the gland revealed high activity, based on the abundance of noticeable secretory granules, either singly or in an aggregated reservoir. In addition, mitochondria were found to intersperse among rich parallel of arrays rough endoplasmic reticulum. Thick cuticle, which was well-delineated and electron dense, apically lined the gland compartments, with discontinuity of the double layer cuticle revealing a trace of secretion discharged into the lumen. Gross anatomy of the adult salivary gland was markedly different from that of the third instar of the same species, and structural dissimilarity is discussed briefly. PMID- 22666548 TI - Gender different response to immunonutrition in liver cirrhosis with sepsis in rats. AB - Females with sepsis have a better prognosis than males, while those of both genders with cirrhosis have a high mortality. Impaired immunity accompanies liver cirrhosis. The potential association between sex and immunologic response of cirrhotic rats in sepsis following immunonutrition was investigated. One hundred and forty-three rats were randomly divided into groups. Liver cirrhosis was produced by weekly feeding of CCl(4) for 8 weeks. Among them, 24 male and 19 female underwent castration one month before studying. The rats were fed with either immune enhancing diet or control diet for five days, then sepsis was induced with cecal ligation and two holes puncture. Main outcomes included mortality and serum cytokines (IL-1beta, 6, and 10). Comparisons were made both within and between genders. Cirrhotic non-castrated male rats showed a significant decrease in mortality (64.1% vs. 32.1%, p = 0.032) with better survival than control diet following immune enhancing diet. Lower mortality of cirrhotic non-castrated female rats was found after immune enhancing diet (69.6% vs. 52.1%, p = 0.365). Cirrhotic castrated male rats showed a lower mortality (44.4%) following immune enhancing diet, and cirrhotic castrated female rats also showed significantly lower mortality and better survival than control diet after immune enhancing diet (87.5% vs. 33.3%, p = 0.004). Plasma concentrations of IL 1beta were higher in non-oophorectomized female rats fed with control diet compared to immune enhancing diet. Non-orchidectomized males and non oophorectomized females exhibited similar increases in IL-10 after immune enhancing diet. Our results demonstrated that immunonutrition was more beneficial for male than female cirrhotic rats following sepsis. Though orchidectomy was not found to be more advantageous for the normal male rats in sepsis, immunonutrition seemed to be as important as sex hormone for female rats in sepsis. PMID- 22666547 TI - Vitamin D and its role during pregnancy in attaining optimal health of mother and fetus. AB - Despite its discovery a hundred years ago, vitamin D has emerged as one of the most controversial nutrients and prohormones of the 21st century. Its role in calcium metabolism and bone health is undisputed but its role in immune function and long-term health is debated. There are clear indicators from in vitro and animal in vivo studies that point to vitamin D's indisputable role in both innate and adaptive immunity; however, the translation of these findings to clinical practice, including the care of the pregnant woman, has not occurred. Until recently, there has been a paucity of data from randomized controlled trials to establish clear cut beneficial effects of vitamin D supplementation during pregnancy. An overview of vitamin metabolism, states of deficiency, and the results of recent clinical trials conducted in the U.S. are presented with an emphasis on what is known and what questions remain to be answered. PMID- 22666550 TI - Features of "All LNA" Duplexes Showing a New Type of Nucleic Acid Geometry. AB - "Locked nucleic acids" (LNAs) belong to the backbone-modified nucleic acid family. The 2'-O,4'-C-methylene-beta-D-ribofuranose nucleotides are used for single or multiple substitutions in RNA molecules and thereby introduce enhanced bio- and thermostability. This renders LNAs powerful tools for diagnostic and therapeutic applications. RNA molecules maintain the overall canonical A-type conformation upon substitution of single or multiple residues/nucleotides by LNA monomers. The structures of "all" LNA homoduplexes, however, exhibit significant differences in their overall geometry, in particular a decreased twist, roll and propeller twist. This results in a widening of the major groove, a decrease in helical winding, and an enlarged helical pitch. Therefore, the LNA duplex structure can no longer be described as a canonical A-type RNA geometry but can rather be brought into proximity to other backbone-modified nucleic acids, like glycol nucleic acids or peptide nucleic acids. LNA-modified nucleic acids provide thus structural and functional features that may be successfully exploited for future application in biotechnology and drug discovery. PMID- 22666551 TI - Pulse wave velocity as marker of preclinical arterial disease: reference levels in a uruguayan population considering wave detection algorithms, path lengths, aging, and blood pressure. AB - Carotid-femoral pulse wave velocity (PWV) has emerged as the gold standard for non-invasive evaluation of aortic stiffness; absence of standardized methodologies of study and lack of normal and reference values have limited a wider clinical implementation. This work was carried out in a Uruguayan (South American) population in order to characterize normal, reference, and threshold levels of PWV considering normal age-related changes in PWV and the prevailing blood pressure level during the study. A conservative approach was used, and we excluded symptomatic subjects; subjects with history of cardiovascular (CV) disease, diabetes mellitus or renal failure; subjects with traditional CV risk factors (other than age and gender); asymptomatic subjects with atherosclerotic plaques in carotid arteries; patients taking anti-hypertensives or lipid-lowering medications. The included subjects (n = 429) were categorized according to the age decade and the blood pressure levels (at study time). All subjects represented the "reference population"; the group of subjects with optimal/normal blood pressures levels at study time represented the "normal population." Results. Normal and reference PWV levels were obtained. Differences in PWV levels and aging-associated changes were obtained. The obtained data could be used to define vascular aging and abnormal or disease-related arterial changes. PMID- 22666553 TI - The autoimmune tautology: from polyautoimmunity and familial autoimmunity to the autoimmune genes. PMID- 22666552 TI - N-domain isoform of Angiotensin I converting enzyme as a marker of hypertension: populational study. AB - The aim of this paper was to investigate the presence of the urinary 90 kDa N domain ACE in a cohort of the population from Vitoria, Brazil, to verify its association with essential hypertension since this isoform could be a possible genetic marker of hypertension. Anthropometric, clinical, and laboratory parameters of the individuals were evaluated (n = 1150) and the blood pressure (BP) was measured. The study population was divided according to ACE isoforms in urine as follows: ACE 65/90/190, presence of three ACE isoforms (n = 795), ACE 90(+) (65/90) (n = 186), and ACE 90(-) (65/190) (n = 169) based on the presence (+) or absence (-) of the 90 kDa ACE isoform. The anthropometric parameters, lipid profile, serum levels of uric acid, glucose, and the systolic and diastolic BP were significantly greater in the ACE 90(+) compared with the ACE 90(-) and ACE 65/90/190 individuals. We found that 98% of individuals from the ACE 90(+) group and 38% from the ACE 65/90/190 group had hypertension, compared to only 1% hypertensive individuals in the ACE 90(-) group. There is a high presence of the 90 kDa N-domain ACE isoform (85%) in the studied population. The percentile of normotensive subjects with three isoforms was 62%. Our findings could contribute to the development of new efficient strategy to prevent and treat hypertension to avoid the development of cardiovascular disease. PMID- 22666554 TI - Is multiple sclerosis an autoimmune disease? AB - Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) with varied clinical presentations and heterogeneous histopathological features. The underlying immunological abnormalities in MS lead to various neurological and autoimmune manifestations. There is strong evidence that MS is, at least in part, an immune-mediated disease. There is less evidence that MS is a classical autoimmune disease, even though many authors state this in the description of the disease. We show the evidence that both supports and refutes the autoimmune hypothesis. In addition, we present an alternate hypothesis based on virus infection to explain the pathogenesis of MS. PMID- 22666555 TI - Blood Pressure Control at Rest and during Exercise in Obese Children and Adults. AB - The hemodynamic responses to exercise have been studied to a great extent over the past decades, and an exaggerated blood pressure response during an acute exercise bout has been considered as an indicator of cardiovascular risk. Obesity is a major factor influencing the blood pressure response to exercise since evidence indicates that the arterial pressure response to exercise is exacerbated in obese compared with lean adults. Signs of augmented responses (such as an exaggerated blood pressure response) to physical exertion appear early in life (from the prepubertal years) in obese individuals. Understanding the mechanisms that drive the altered hemodynamic responses during exercise in obese individuals and prevent the progression to hypertension is vitally important. This paper focuses on the evidence linking obesity with alterations of the autonomic nervous system and discusses the potential mechanisms and consequences of the altered sympathetic nervous system behavior in obese individuals at rest and during exercise. Furthermore, this paper presents the alterations in the reflex regulatory mechanisms ("exercise pressor reflex" and baroreflex) in obese children and adults and addresses the effects of training on obesity-related disturbances. PMID- 22666556 TI - Being Normal Weight but Feeling Overweight in Adolescence May Affect Weight Development into Young Adulthood-An 11-Year Followup: The HUNT Study, Norway. AB - Objectives. To explore if self-perceived overweight in normal weight adolescents influence their weight development into young adulthood and if so, whether physical activity moderates this association. Methods. A longitudinal study of 1196 normal weight adolescents (13-19 yrs) who were followed up as young adults (24-30 yrs) in the HUNT study. Lifestyle and health issues were assessed employing questionnaires, and standardized anthropometric measurements were taken. Chi square calculations and regression analyses were performed to investigate the associations between self-perceived overweight and change in BMI or waist circumference (WC) adjusted for age, age squared, sex, and other relevant cofactors. Results. Adolescents, defined as being normal weight, but who perceived themselves as overweight had a larger weight gain into young adulthood than adolescents who perceived themselves as normal weight (difference in BMI: 0.66 units [CI95%: 0.1, 1.2] and in WC: 3.46 cm [CI95%: 1.8, 5.1]). Level of physical activity was not found to moderate this association. Conclusions. This study reveals that self-perceived overweight during adolescence may affect development of weight from adolescence into young adulthood. This highlights the importance of also focusing on body image in public health interventions against obesity, favouring a "healthy" body weight taking into account natural differences in body shapes. PMID- 22666557 TI - Age-Related Decline in Cardiorespiratory Fitness among Career Firefighters: Modification by Physical Activity and Adiposity. AB - Firefighting is a very hazardous occupation, and strenuous fire duties require high levels of physical fitness. In the general adult population, cardiorespiratory fitness (CRF) declines with aging. We sought to investigate the effect of increasing age on CRF in male career firefighters as well as the modifying effects of physical activity and adiposity. We cross-sectionally examined 804 male career firefighters from two Midwestern states. CRF was determined from symptom-limited maximal treadmill exercise testing in metabolic equivalents (METS) following the Bruce protocol. Physical activity self-reports were extracted from responses to a health and lifestyle questionnaire. We found as expected that CRF declines with advancing age; however, the decline is greatly attenuated among leaner firefighters who report more physical activity. Furthermore, in a linear regression model including age, BMI, and variables describing physical activity behaviors, we could predict CRF (R(2) = 0.6286). The total weekly duration of aerobic exercise as well as the duration of weight lifting sessions both had significant impacts on age-related decline. We conclude that firefighters are more likely to maintain the high levels of CRF needed to safely perform their duties if they engage in frequent exercise and maintain healthy weights. PMID- 22666558 TI - Home Availability and the Impact of Weekly Stressful Events Are Associated with Fruit and Vegetable Intake among African American and Hispanic/Latina Women. AB - Background. Mediating and moderating variables may interfere with the association between neighborhood availability of grocery stores (NAG) and supermarkets (NAS) and fruit and vegetable (FV) intake. Objective. The purpose of this study was to test mediation of home availability of FV (HAFV) and moderation of impact of weekly stressful events (IWSE) on the association between NAG and NAS with FV consumption among African American (AA) and Hispanic/Latina (HL) women. Methods. Three hundred nine AA and HL, 25-60 year old women in the Health Is Power (HIP) randomized controlled trial completed validated measures of HAFV, IWSE, and FV intake at baseline. Trained field assessors coded NAG and NAS. Institutional Review Board approval was obtained. Results. NAG and NAS were not associated with FV intake or HAFV, so HAFV was not a mediator. HAFV (std. Beta = .29, P < 0.001) and IWSE (std. Beta = .17; P < 0.05) were related to FV intake (R(2) = 0.17; P < 0.001), but IWSE was not a moderator. Conclusion. Increasing HAFV and decreasing the IWSE should increase FV consumption. The extent to which the neighborhood environment is related to the home food environment and diet, and the mechanisms for the association between IWSE and diet should be examined in future research. PMID- 22666559 TI - Physical activity is associated with weight loss and increased cardiorespiratory fitness in severely obese men and women undergoing lifestyle treatment. AB - We aimed to examine the relationship between physical activity (PA) and change in body weight and cardiorespiratory fitness (CRF) in severely obese men and women. Thirty-five subjects (10 men, body mass index 43.2 +/- 5.1 kg/m(2)) who participated in a 10-month lifestyle treatment programme were included. The PA duration correlated only with weight change for men (r = -0.69, P = .027 versus r = -0.19, P = .372 for women). Conversely, the PA intensity correlated only with CRF for women (r = 0.61, P = .003 versus r = 0.39, P = .340 for men). PA explained 55.8 and 5.6% of weight change for men and women, respectively, whereas the corresponding explained variances for CRF were 15.6 and 36.7%. We conclude that PA was associated with change in body weight and CRF; however, there was a trend towards a gender specific effect between severely obese men and women. PMID- 22666560 TI - The acute and residual effect of a single exercise session on meal glucose tolerance in sedentary young adults. AB - The study goals were to (1) establish the variability in postprandial glucose control in healthy young people consuming a mixed meal and, then (2) determine the acute and residual impact of a single exercise bout on postprandial glucose control. In study 1, 18 people completed two similar mixed meal trials and an intravenous glucose tolerance test (IVGTT). There were strong test-retest correlations for the post-meal area under the curve (AUC) for glucose, insulin, and Cpeptide (r = 0.73-0.83) and the Matsuda insulin sensitivity index (ISI, r = 0.76), and between meal and IVGTT-derived ISI (r = 0.83). In study 2, 11 untrained young adults completed 3 trials. One trial (No Ex) was completed after refraining from vigorous activity for >=3 days. On the other 2 trials, a 45-min aerobic exercise bout was performed either 17-hours (Prior Day Ex) or 1-hour (Same Day Ex) before consuming the test meal. Compared to No Ex and Prior Day Ex, which did not differ from one another, there were lower AUCs on the Same Day Ex trial for glucose (6%), insulin (20%) and C-peptide (14%). Thus, a single moderate intensity exercise session can acutely improve glycemic control but the effect is modest and short-lived. PMID- 22666561 TI - Developmental origins of health and disease. PMID- 22666562 TI - Causes of Death in HIV Patients and the Evolution of an AIDS Hospice: 1988-2008. AB - This paper reports on the transformation that has occurred in the care of people living with HIV/AIDS in a Toronto Hospice. Casey House opened in the pre-HAART era to care exclusively for people with HIV/AIDS, an incurable disease. At the time, all patients were admitted for palliative care and all deaths were due to AIDS-defining conditions. AIDS-defining malignancies accounted for 22 percent of deaths, mainly, Kaposi sarcoma and lymphoma. In the post-HAART era, AIDS-defining malignancies dropped dramatically and non-AIDS-defining malignancies became a significant cause of death, including liver cancer, lung cancer and gastric cancers. In the post-HAART era, people living with HIV/AIDS served at Casey House have changed considerably, with increasing numbers of patients facing homelessness and mental health issues, including substance use. Casey House offers a picture of the evolving epidemic and provides insight into changes and improvements made in the care of these patients. PMID- 22666563 TI - HIV Clients as Agents for Prevention: A Social Network Solution. AB - HIV prevention efforts to date have not explored the potential for persons living with HIV to act as change agents for prevention behaviour in their social networks. Using egocentric social network analysis, this study examined the prevalence and social network correlates of prevention advocacy behaviours (discussing HIV in general; encouraging abstinence or condom use, HIV testing, and seeking HIV care) enacted by 39 HIV clients in Uganda. Participants engaged in each prevention advocacy behaviour with roughly 50-70% of the members in their network. The strongest determinant of engaging in prevention advocacy with more of one's network members was having a greater proportion of network members who knew one's HIV seropositive status, as this was associated with three of the four advocacy behaviours. These findings highlight the potential for PLHA to be key change agents for HIV prevention within their networks and the importance of HIV disclosure in facilitating prevention advocacy. PMID- 22666565 TI - Evaluation of three adolescent sexual health programs in ha noi and khanh hoa province, Vietnam. AB - With an increase in sexual activity among young adults in Vietnam and associated risks, there is a need for evidence-based sexual health interventions. This evaluation of three sexual health programs based on the Protection Motivation Theory (PMT) was conducted in 12 communes in Ha Noi, Nha Trang City, and Ninh Hoa District. Inclusion criteria included unmarried youth 15-20 years residing in selected communes. Communes were randomly allocated to an intervention, and participants were randomly selected within each commune. The intervention programs included Vietnamese Focus on Kids (VFOK), the gender-based program Exploring the World of Adolescents (EWA), and EWA plus parental and health provider education (EWA+). Programs were delivered over a ten-week period in the communities by locally trained facilitators. The gender-based EWA program with parental involvement (EWA+) compared to VFOK showed significantly greater increase in knowledge. EWA+ in comparison to VFOK also showed significant decrease at immediate postintervention for intention to have sex. Sustained changes are observed in all three interventions for self-efficacy condom use, self-efficacy abstinence, response efficacy for condoms, extrinsic rewards, and perceived vulnerability for HIV. These findings suggest that theory-based community programs contribute to sustained changes in knowledge and attitudes regarding sexual risk among Vietnamese adolescents. PMID- 22666564 TI - Interactive Effects of Morphine on HIV Infection: Role in HIV-Associated Neurocognitive Disorder. AB - HIV epidemic continues to be a severe public health problem and concern within USA and across the globe with about 33 million people infected with HIV. The frequency of drug abuse among HIV infected patients is rapidly increasing and is another major issue since injection drug users are at a greater risk of developing HIV associated neurocognitive dysfunctions compared to non-drug users infected with HIV. Brain is a major target for many of the recreational drugs and HIV. Evidences suggest that opiate drug abuse is a risk factor in HIV infection, neural dysfunction and progression to AIDS. The information available on the role of morphine as a cofactor in the neuropathogenesis of HIV is scanty. This review summarizes the results that help in understanding the role of morphine use in HIV infection and neural dysfunction. Studies show that morphine enhances HIV-1 infection by suppressing IL-8, downregulating chemokines with reciprocal upregulation of HIV coreceptors. Morphine also activates MAPK signaling and downregulates cAMP response element-binding protein (CREB). Better understanding on the role of morphine in HIV infection and mechanisms through which morphine mediates its effects may help in devising novel therapeutic strategies against HIV-1 infection in opiate using HIV-infected population. PMID- 22666566 TI - Study Design of the Microcirculatory Shock Occurrence in Acutely Ill Patients (microSOAP): an International Multicenter Observational Study of Sublingual Microcirculatory Alterations in Intensive Care Patients. AB - Objective. Sublingual microcirculatory alterations are associated with an adverse prognosis in several critical illness subgroups. Up to now, single-center studies have reported on sublingual microcirculatory alterations in ICU patient subgroups, but an extensive evaluation of the prevalence of these alterations is lacking. We present the study design of an international multicenter observational study to investigate the prevalence of microcirculatory alterations in critically ill: the Microcirculatory Shock Occurrence in Acutely ill Patients (microSOAP). Methods. 36 ICU's worldwide have participated in this study aiming for inclusion of over 500 evaluable patients. To enable communication and data collection, a website, an Open Clinica 3.0 database, and image uploading software have been designed. A one-session assessment of the sublingual microcirculation using Sidestream Dark Field imaging and data collection on patient characteristics has been performed in every ICU patient >18 years, regardless of underlying disease. Statistical analysis will provide insight in the prevalence and severity of sublingual alterations, its relation to systemic hemodynamic variables, disease, therapy, and outcome. Conclusion. This study will be the largest microcirculation study ever performed. It is expected that this study will also establish a basis for future studies related to the microcirculation in critically ill. PMID- 22666567 TI - High-flow nasal interface improves oxygenation in patients undergoing bronchoscopy. AB - During bronchoscopy hypoxemia is commonly found and oxygen supply can be delivered by interfaces fed with high gas flows. Recently, the high-flow nasal cannula (HFNC) has been introduced for oxygen therapy in adults, but they have not been used so far during bronchoscopy in adults. Forty-five patients were randomly assigned to 3 groups receiving oxygen: 40 L/min through a Venturi mask (V40, N = 15), nasal cannula (N40, N = 15), and 60 L/min through a nasal cannula (N60, N = 15) during bronchoscopy. Gas exchange and circulatory variables were sampled before (FiO(2) = 0.21), at the end of bronchoscopy (FiO(2) = 0.5), and thereafter (V40, FiO(2) = 0.35). In 8 healthy volunteers oxygen was randomly delivered according to V40, N40, and N60 settings, and airway pressure was measured. At the end of bronchoscopy, N60 presented higher PaO(2), PaO(2)/FiO(2), and SpO(2) than V40 and N40 that did not differ between them. In the volunteers (N60) median airway pressure amounted to 3.6 cmH(2)O. Under a flow rate of 40 L/min both the Venturi mask and HFNC behaved similarly, but nasal cannula associated with a 60 L/min flow produced the better results, thus indicating its use in mild respiratory dysfunctions. PMID- 22666569 TI - Variability in Uremic Control during Continuous Venovenous Hemodiafiltration in Trauma Patients. AB - Introduction. Acute kidney injury (AKI) necessitating continuous renal replacement therapy (CRRT) is a severe complication in trauma patients (TP). We wanted to assess daily duration of CRRT and its impact on uremic control in TP. Material and Methods. We retrospectively reviewed adult TP, with or without rhabdomyolysis, with AKI undergoing CRRT. Data on daily CRRT duration and causes for temporary stops were collected from the first five CRRT days. Uremic control was assessed by daily changes in serum urea (Deltaurea) and creatinine (Deltacreatinine) concentrations. Results. Thirty-six TP were included with a total of 150 CRRT days, 17 (43%) with rhabdomyolysis. The median (interquartile range (IQR)) time per day with CRRT was 19 (15-21) hours. There was a significant correlation between daily CRRT duration and Deltaurea (r = 0.60, P<=0.001) and Deltacreatinine (r = 0.43; P = 0.012). CRRT pauses were caused by filter clotting (54%), therapeutic interventions (25%), catheter related problems (10%), filter timeout (6%), and diagnostic procedures (6%). Rhabdomyolysis did not affect the CRRT data. Conclusions. TP undergoing CRRT had short daily CRRT duration causing reduced uremic control. Clinicians should modify their daily clinical practice to improve technical skills and achieve sufficient dialysis dose. PMID- 22666568 TI - The end-organ impairment in liver cirrhosis: appointments for critical care. AB - Liver cirrhosis (LC) can lead to a clinical state of liver failure, which can exacerbate through the course of the disease. New therapies aimed to control the diverse etiologies are now more effective, although the disease may result in advanced stages of liver failure, where liver transplantation (LT) remains the most effective treatment. The extended lifespan of these patients and the extended possibilities of liver support devices make their admission to an intensive care unit (ICU) more probable. In this paper the LC is approached from the point of view of the pathophysiological alterations present in LC patients previous to ICU admission, particularly cardiovascular, but also renal, coagulopathic, and encephalopathic. Infections and available liver detoxifications devices also deserve mentioning. We intend to contribute towards ICU physician readiness to the care for this particular type of patients, possibly in dedicated ICUs. PMID- 22666570 TI - Left ventricular diastolic dysfunction in the intensive care unit: trends and perspectives. AB - Heart failure with a normal or nearly normal left ventricular (LV) ejection fraction (HFNEF) may represent more than 50% of heart failure cases. Although HFNEF is being increasingly recognized, there is a relative lack of information regarding its incidence and prognostic implications in intensive care unit (ICU) patients. In the ICU, many factors related to patient's history, or applied therapies, may induce or aggravate LV diastolic dysfunction. This may impact on patients' morbidity and mortality. This paper discusses methods for assessing LV diastolic function and the feasibility of their implementation for diagnosing HFNEF in the ICU. PMID- 22666571 TI - Investigational Paradigms in Downscoring and Upscoring DCIS: Surgical Management Review. AB - Counseling patients with DCIS in a rational manner can be extremely difficult when the range of treatment criteria results in diverse and confusing clinical recommendations. Surgeons need tools that quantify measurable prognostic factors to be used in conjunction with clinical experience for the complex decision making process. Combination of statistically significant tumor recurrence predictors and lesion parameters obtained after initial excision suggests that patients with DCIS can be stratified into specific subsets allowing a scientifically based discussion. The goal is to choose the treatment regimen that will significantly benefit each patient group without subjecting the patients to unnecessary risks. Exploring the effectiveness of complete excision may offer a starting place in a new way of reasoning and conceiving surgical modalities in terms of "downscoring" or "upscoring" patient risk, perhaps changing clinical approach. Reexcison may lower the specific subsets' score and improve local recurrence-free survival also by revealing a larger tumor size, a higher nuclear grade, or an involved margin and so suggesting the best management. It seems, that the key could be identifying significant relapse predictive factors, according to validated risk investigation models, whose value is modifiable by the surgical approach which avails of different diagnostic and therapeutic potentials to be optimal. Certainly DCIS clinical question cannot have a single curative mode due to heterogeneity of pathological lesions and histologic classification. PMID- 22666572 TI - A Primer on the Current State-of-the-Science Neoadjuvant and Adjuvant Therapy for Patients with Locally Advanced Rectal Adenocarcinomas. AB - Patients with rectal cancers, due to the unique location of the tumor, have a recurrence pattern distinct from colon cancers. Advances in adjuvant therapy over the last three decades have played an important role in improving patient outcomes. This article serves to review the clinical studies that lay the basis for our current standard-of-care treatment of patients with locally advanced rectal cancer, as well as touch upon future ongoing experimental clinical trials of adjuvant chemoradiation therapy. PMID- 22666573 TI - The use of split-thickness skin grafts on diabetic foot ulcerations: a literature review. AB - Diabetic foot ulcerations are historically difficult to treat despite advanced therapeutic modalities. There are numerous modalities described in the literature ranging from noninvasive topical wound care to more invasive surgical procedures such as primary closure, skin flaps, and skin grafting. While skin grafting provides faster time to closure with a single treatment compared to traditional topical wound treatments, the potential risks of donor site morbidity and poor wound healing unique to the diabetic state have been cited as a contraindication to its widespread use. In order to garner clarity on this issue, a literature review was undertaken on the use of split-thickness skin grafts on diabetic foot ulcers. Search of electronic databases yielded four studies that reported split thickness skin grafts as definitive means of closure. In addition, several other studies employed split-thickness skin grafts as an adjunct to a treatment that was only partially successful or used to fill in the donor site of another plastic surgery technique. When used as the primary closure on optimized diabetic foot ulcerations, split-thickness skin grafts are 78% successful at closing 90% of the wound by eight weeks. PMID- 22666574 TI - Buruli-ulcer induced disability in ghana: a study at apromase in the ashanti region. AB - Objectives. To describe trends and category of disabilities caused by Buruli ulcer disease. Design. This retrospective study was set up to quantify information on the disability trends caused by Buruli ulcer (BU) using data on patients attending BU and chronic ulcer clinics from 2004 to 2009, at Global Evangelical Mission Hospital, Apromase. Methods. Data was retrieved from the WHO BU1 form, case registry book, surgical theatre register, and BU patients' records book of the hospital. Disability was measured as the incapability of patients to perform one or more daily activities due to his/her state of BU disease before treatment. Results. A total of 336 positive BU cases comprising 181 males (53.9%) were recorded of which 113 (33.6%) cases of disabilities were identified. A mean age of 52.5 (+/-1.32) years was recorded. For the trend of disabilities, the year 2009 recorded the highest (N = 34, 31.0%). The lesions were mostly located at the lower limbs (N = 65, 57.5%) region of the patients. Lesions with diameter >15 cm were the major (59.3%) category of lesions. Conclusion. Trend of disability reveals proportional increase over the years from 2004 to 2009. Contracture at the knee and ankle joints was the commonest disability recorded. PMID- 22666575 TI - Pathological perspective of drug-eluting stent thrombosis. AB - Although very late stent thrombosis (VLST) after drug-eluting stent (DES) implantation remains a major concern, the precise mechanisms have not been clarified. An association between late acquired incomplete stent apposition (ISA) and VLST of DES has been suggested by several intravascular ultrasound studies demonstrating very high prevalence of ISA in the setting of VLST. To clarify the pathological mechanisms of VLST, we investigated vascular responses of coronary arteries of VLST cases after DES implantation. PMID- 22666576 TI - Factor v leiden and inflammation. AB - Factor V Leiden, is a variant of human factor V (FV), also known as proaccelerin, which leads to a hypercoagulable state. Along these years, factor V Leiden (FVL) has been studied from the pathophysiologic point of view, and research has been focused on finding clinical approaches for the management of the FVL associated to a trombophilic state. Less attention has been paid about the possible role of FVL in inflammatory conditions known to be present in different disorders such as uremia, cirrhosis, liver transplantation, depression as well as sepsis, infection or, inflammatory bowel disease (IBD). Whether platelet FVL will increase the activation of coagulation and/or in which proportion is able to determine the final outcome in the previously mentioned inflammatory conditions is a subject that remains uncertain. This paper will review the association of FVL with inflammation. Specifically, it will analyze the important role of the endothelium and the contribution of other inflammatory components involved at both the immune and vascular levels. This paper will also try to emphasize the importance of being a FVL carrier in associations to diseases where a chronic inflammation occurs, and how this condition may be determinant in the progression and outcome of a specific clinic situation. PMID- 22666577 TI - The PCR-Based Diagnosis of Central Nervous System Tuberculosis: Up to Date. AB - Central nervous system (CNS) tuberculosis, particularly tuberculous meningitis (TBM), is the severest form of Mycobacterium tuberculosis (M.Tb) infection, causing death or severe neurological defects in more than half of those affected, in spite of recent advancements in available anti-tuberculosis treatment. The definitive diagnosis of CNS tuberculosis depends upon the detection of M.Tb bacilli in the cerebrospinal fluid (CSF). At present, the diagnosis of CNS tuberculosis remains a complex issue because the most widely used conventional "gold standard" based on bacteriological detection methods, such as direct smear and culture identification, cannot rapidly detect M.Tb in CSF specimens with sufficient sensitivity in the acute phase of TBM. Recently, instead of the conventional "gold standard", the various molecular-based methods including nucleic acid amplification (NAA) assay technique, particularly polymerase chain reaction (PCR) assay, has emerged as a promising new method for the diagnosis of CNS tuberculosis because of its rapidity, sensitivity and specificity. In addition, the innovation of nested PCR assay technique is worthy of note given its contribution to improve the diagnosis of CNS tuberculosis. In this review, an overview of recent progress of the NAA methods, mainly highlighting the PCR assay technique, was presented. PMID- 22666578 TI - The role of foxp3-expressing regulatory T cells and T helpers in immunopathogenesis of multidrug resistant pulmonary tuberculosis. AB - Subpopulation structure of regulatory T cells and T helpers of peripheral blood in patients with newly diagnosed pulmonary tuberculosis depending on the clinical form of disease and sensitivity of Mycobacterium tuberculosis to antituberculosis drugs has been analyzed in this work. It has been shown that the leading part in immune suppression at infiltrative, dissemination, and fibrosis-cavity pulmonary tuberculosis is played by natural regulatory CD4(+)CD25(+)Foxp3(+)-T lymphocytes. Thus we estimate increase of their number in blood by drug-resistance and drug susceptible patients. It has been demonstrated that in patients with fibrocavernous and infiltrative form of the disease and drug-resistant pulmonary tuberculosis the number of CD4(+)CD25(-)Foxp3(+)-regulatory T cells was increasing. In patients with infiltrative pulmonary tuberculosis, including multidrug-resistant M. tuberculosis, an increased number of CD3(+)CD4(+)CD25(-) T helpers is determined by the pathogenic features of the development of the tuberculosis infection and is connected with the activation of Th1-dependent immune response. Reduction in the number of T-helpers in the blood of patients with dissemination and fibrosis-cavity pulmonary tuberculosis mediates inefficient implementation of cell-mediated protective immunity. PMID- 22666579 TI - Interaction between Mu and Delta Opioid Receptor Agonists in an Assay of Capsaicin-Induced Thermal Allodynia in Rhesus Monkeys. AB - Delta opioid agonists enhance antinociceptive effects of mu-opioid agonists in many preclinical assays of acute nociception, but delta/mu interactions in preclinical models of inflammation-associated pain have not been examined. This study examined interactions between the delta agonist SNC80 [(+)-4-[(alphaR) alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N diethylbenzamide] and the mu agonist analgesics methadone, morphine, and nalbuphine in an assay of capsaicin-induced thermal allodynia in rhesus monkeys. Thermal allodynia was produced by topical application of capsaicin to the tail. Antiallodynic effects of methadone, morphine, and nalbuphine were evaluated alone or in combination with fixed proportions of SNC80 identical to proportions previously shown to enhance acute thermal antinociceptive effects of these mu agonists in rhesus monkeys (0.9 : 1 SNC80/methadone; 0.29 : 1 SNC80/morphine; 3.6 : 1 SNC80/nalbuphine). Methadone, morphine, and nalbuphine each produced dose dependent antiallodynia. SNC80 produced partial antiallodynia up to the highest dose tested (5.6 mg/kg). SNC80 produced a modest, enantioselective, and naltrindole-reversible enhancement of methadone-induced antiallodynia. However, SNC80 did not enhance morphine antiallodynia and only weakly enhanced nalbuphine antiallodynia. Overall, SNC80 produced modest or no enhancement of the antiallodynic effects of the three mu agonists evaluated. These results suggest that delta agonist-induced enhancement of mu agonist antiallodynia may be weaker and less reliable than previously demonstrated enhancement of mu agonist acute thermal nociception. PMID- 22666580 TI - Renal Function in Relation to Cardiac (123)I-MIBG Scintigraphy in Patients with Chronic Heart Failure. AB - The aim of this study was to explore if estimates of renal function could explain variability of (123)I-metaiodobenzylguanidine ((123)I-MIBG) assessed myocardial sympathetic activity. Furthermore estimates of renal function were compared to (123)I-MIBG as predictors of cardiac death in chronic heart failure (CHF). Semi quantitative parameters of (123)I-MIBG myocardial uptake and washout were calculated using early heart/mediastinum ratio (H/M), late H/M and washout. Renal function was calculated as estimated Creatinine Clearance (e-CC) and as estimated Glomerular Filtration Rate (e-GFR). Thirty-nine patients with CHF (24 males; age: 64.4 +/- 10.5 years; NYHA II/III/IV: 17/20/2; LVEF: 24.0 +/- 11.5%) were studied. Variability in any of the semi-quantitative (123)I-MIBG myocardial parameters could not be explained by e-CC or e-GFR. During follow-up (60 +/- 37 months) there were 6 cardiac deaths. Cox proportional hazard regression analysis showed that late H/M was the only independent predictor for cardiac death (Chi-square 3.2, regression coefficient: -4.095; standard error: 2.063; hazard ratio: 0.17 [95% CI: 0.000-0.950]). Addition of estimates of renal function did not significantly change the Chi-square of the model. Semi-quantitative (123)I-MIBG myocardial parameters are independent of estimates of renal function. In addition, cardiac sympathetic innervation assessed by (123)I-MIBG scintigraphy seems to be superior to renal function in the prediction of cardiac death in CHF patients. PMID- 22666581 TI - Use of FDG-PET in Radiation Treatment Planning for Thoracic Cancers. AB - Radiotherapy plays an important role in the treatment for thoracic cancers. Accurate diagnosis is essential to correctly perform curative radiotherapy. Tumor delineation is also important to prevent geographic misses in radiotherapy planning. Currently, planning is based on computed tomography (CT) imaging when radiation oncologists manually contour the tumor, and this practice often induces interobserver variability. F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) has been reported to enable accurate staging and detect tumor extension in several thoracic cancers, such as lung cancer and esophageal cancer. FDG-PET imaging has many potential advantages in radiotherapy planning for these cancers, because it can add biological information to conventional anatomical images and decrease the inter-observer variability. FDG-PET improves radiotherapy volume and enables dose escalation without causing severe side effects, especially in lung cancer patients. The main advantage of FDG-PET for esophageal cancer patients is the detection of unrecognized lymph node or distal metastases. However, automatic delineation by FDG-PET is still controversial in these tumors, despite the initial expectations. We will review the role of FDG-PET in radiotherapy for thoracic cancers, including lung cancer and esophageal cancer. PMID- 22666582 TI - Cardiopulmonary exercise testing in lung transplantation: a review. AB - There has been an increase in lung transplantation in the USA. Lung allocation is guided by the lung allocation score (LAS), which takes into account one measure of exercise capacity, the 6-minute walk test (6MWT). There is a paucity of data regarding the role and value of cardiopulmonary stress test (CPET) in the evaluation of lung transplant recipients while on the transplant waiting list and after lung transplantation. While clearly there is a need for further prospective investigation, the available literature strongly suggests a potential role for CPET in the setting of lung transplant. PMID- 22666583 TI - Thoracomyoplasty in the treatment of empyema: current indications, basic principles, and results. AB - Empyema remains a challenge for modern medicine. Cases not amenable to lung decortication are particularly difficult to treat, requiring prolonged hospitalizations and mutilating procedures. This paper presents the current role of thoracomyoplasty procedures, which allow complete and definitive obliteration of the infected pleural space by a combination of thoracoplasty and the use of neighbourhood muscle flaps (latissimus dorsi, serratus anterior, pectoralis, rectus abdominis, omentum, etc). Recent publications show an overall rate of success of 90%, with a quick and definitive healing. Although rarely indicated in our days, this kind of procedures remain in the armamentarium of modern thoracic surgery. The importance of thoracomyoplasty derives from the fact that it may be a simple and definitive solution for complicated cases of chronic empyema not amenable to standard decortication. PMID- 22666584 TI - Validity of reporting oxygen uptake efficiency slope from submaximal exercise using respiratory exchange ratio as secondary criterion. AB - Background. Oxygen uptake efficiency slope (OUES) is a reproducible, objective marker of cardiopulmonary function. OUES is reported as being relatively independent of exercise intensity. Practical guidance and criteria for reporting OUES from submaximal tests has not been established. Objective. Evaluate the use of respiratory exchange ratio (RER) as a secondary criterion for reporting OUES. Design. 100 healthy volunteers (53 women) completed a ramped treadmill protocol to exhaustive exercise. OUES was calculated from data truncated to RER levels from 0.85 to 1.2 and compared to values generated from full test data. Results. Mean (sd) OUES from full test data and data truncated to RER 1.0 and RER 0.9 was 2814 (718), 2895 (730), and 2810 (789) mL/min per 10-fold increase in VE, respectively. Full test OUES was highly correlated with OUES from RER 1.0 (r = 0.9) and moderately correlated with OUES from RER 0.9 (r = 0.79). Conclusion. OUES values peaked in association with an RER level of 1.0. Sub-maximal OUES values are not independent of exercise intensity. There is a significant increase in OUES value as exercise moves from low to moderate intensity. RER can be used as a secondary criterion to define this transition. PMID- 22666585 TI - Programmed Necrosis: A Prominent Mechanism of Cell Death following Neonatal Brain Injury. AB - Despite the introduction of therapeutic hypothermia, neonatal hypoxic ischemic (HI) brain injury remains a common cause of developmental disability. Development of rational adjuvant therapies to hypothermia requires understanding of the pathways of cell death and survival modulated by HI. The conceptualization of the apoptosis-necrosis "continuum" in neonatal brain injury predicts mechanistic interactions between cell death and hydrid forms of cell death such as programmed or regulated necrosis. Many of the components of the signaling pathway regulating programmed necrosis have been studied previously in models of neonatal HI. In some of these investigations, they participate as part of the apoptotic pathways demonstrating clear overlap of programmed death pathways. Receptor interacting protein (RIP)-1 is at the crossroads between types of cellular death and survival and RIP-1 kinase activity triggers formation of the necrosome (in complex with RIP-3) leading to programmed necrosis. Neuroprotection afforded by the blockade of RIP-1 kinase following neonatal HI suggests a role for programmed necrosis in the HI injury to the developing brain. Here, we briefly review the state of the knowledge about the mechanisms behind programmed necrosis in neonatal brain injury recognizing that a significant proportion of these data derive from experiments in cultured cell and some from in vivo adult animal models. There are still more questions than answers, yet the fascinating new perspectives provided by the understanding of programmed necrosis in the developing brain may lay the foundation for new therapies for neonatal HI. PMID- 22666586 TI - Controversies in the surgical management of spinal cord injuries. AB - Traumatic spinal cord injury (SCI) affects over 200,000 people in the USA and is a major source of morbidity, mortality, and societal cost. Management of SCI includes several components. Acute management includes medical agents and surgical treatment that usually includes either all or a combination of reduction, decompression, and stabilization. Physical therapy and rehabilitation and late onset SCI problems also play a role. A review of the literature in regard to surgical management of SCI patients in the acute setting was undertaken. The controversy surrounding whether reduction is safe, or not, and whether prereduction magnetic resonance (MR) imaging to rule out traumatic disc herniation is essential is discussed. The controversial role of timing of surgical intervention and the choice of surgical approach in acute, incomplete, and acute traumatic SCI patients are reviewed. Surgical treatment is an essential tool in management of SCI patients and the controversy surrounding the timing of surgery remains unresolved. Presurgical reduction is considered safe and essential in the management of SCI with loss of alignment, at least as an initial step in the overall care of a SCI patient. Future prospective collection of outcome data that would suffice as evidence-based is recommended and necessary. PMID- 22666587 TI - The Neuroinflammatory Response in ALS: The Roles of Microglia and T Cells. AB - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by upper and lower motoneuron death. Mutations in the gene for superoxide dismutase 1 (SOD1) cause a familial form of ALS and have been used to develop transgenic mice which overexpress human mutant SOD1 (mSOD) and these mice exhibit a motoneuron disease which is pathologically and phenotypically similar to ALS. Neuroinflammation is a pathological hallmark of many neurodegenerative diseases including ALS and is typified by the activation and proliferation of microglia and the infiltration of T cells into the brain and spinal cord. Although the neuroinflammatory response has been considered a consequence of neuronal dysfunction and death, evidence indicates that manipulation of this response can alter disease progression. Previously viewed as deleterious to neuronal survival, recent reports suggest a trophic role for activated microglia in the mSOD mouse during the early stages of disease that is dependent on instructive signals from infiltrating T cells. However, at advanced stages of disease, activated microglia acquire increased neurotoxic potential, warranting further investigation into factors capable of skewing microglial activation towards a neurotrophic phenotype as a means of therapeutic intervention in ALS. PMID- 22666588 TI - Undetected common mental disorders in long-term sickness absence. AB - Background. Undetected Common Mental Disorders (CMDs) amongst people on sick leave complicate rehabilitation and return to work because appropriate treatments are not initiated. Aims. The aim of this study is to estimate (1) the frequencies of CMD, (2) the predictors of undetected CMD, and (3) the rate of return to work among sick listed individuals without a psychiatric disorder, who are registered on long-term sickness absence (LSA). Methods. A total of 2,414 incident individuals on LSA with a response rate of 46.4%, were identified for a two-phase study. The subsample of this study involved individuals registered on LSA who were sick-listed without a psychiatric sick leave diagnosis. In this respect, Phase 1 included 831 individuals, who were screened for mental disorders. In Phase 2, following the screening of Phase 1, 227 individuals were thoroughly examined by a psychiatrist applying Present State Examination. The analyses of the study were carried out based on the 227 individuals from Phase 2 and, subsequently, weighted to be representative of the 831 individuals in Phase 1. Results. The frequencies of undetected mental disorders among all sick-listed individuals were for any psychiatric diagnosis 21%, depression 14%, anxiety 4%, and somatoform disorder 6%. Conclusions. Undetected CMD may delay the initiation of appropriate treatment and complicate the rehabilitation and return to work. PMID- 22666589 TI - Predictive Molecular Tumour Testing: What Are the Obstacles between Bench and Bedside? AB - There have been many exciting new breakthroughs in understanding tumour biology. This has opened up the possibility of personalized treatment for people with certain tumours. The epidermal growth factor receptor (EGFR) and K-ras are two such targets that can help classify tumours on a molecular basis and guide treatment decisions. However, there are still questions about how best to implement new molecular tests like these to characterize tumours in clinical practice. Potential obstacles include availability of good quality tissue specimens, access to the right test, and consensus about interpretation, funding, and availability. In this paper, we review these issues, by discussing these two examples in detail and suggest some actions for addressing potential barriers. PMID- 22666590 TI - Relationship between Plasma Leptin Level and Chronic Kidney Disease. AB - Background. Leptin is an adipose tissue-derived hormone shown to be related to several metabolic, inflammatory, and hemostatic factors related to chronic kidney disease. Recent animal studies have reported that infusion of recombinant leptin into normal rats for 3 weeks fosters the development of glomerulosclerosis. However, few studies have examined the association between leptin and CKD in humans. Therefore, we examined the association between plasma leptin levels and CKD in a representative sample of US adults. Methods. We examined the third National Health and Nutrition Examination Survey participants >20 years of age (n = 5820, 53.6% women). Plasma leptin levels were categorized into quartiles (<=4.3 Fg/L, 4.4-8.7 Fg/L, 8.8-16.9 Fg/L, >16.9 Fg/L). CKD was defined as a glomerular filtration rate of <60 mL/min/1.73 m(2) estimated from serum creatinine. Results. Higher plasma leptin levels were associated with CKD after adjusting for age, sex, race/ethnicity, education, smoking, alcohol intake, body mass index (BMI), diabetes, hypertension, and serum cholesterol. Compared to quartile 1 of leptin (referent), the odds ratio (95% confidence interval) of CKD associated with quartile 4 was 3.31 (1.41 to 7.78); P-trend = 0.0135. Subgroup analyses examining the relation between leptin and CKD by gender, BMI categories, diabetes, and hypertension status also showed a consistent positive association. Conclusion. Higher plasma leptin levels are associated with CKD in a representative sample of US adults. PMID- 22666591 TI - Intermuscular adipose tissue is muscle specific and associated with poor functional performance. AB - Purpose. People with obesity, diabetes, and peripheral neuropathy have high levels of intermuscular adipose tissue (IMAT) volume which has been inversely related to physical function. We determined if IMAT is muscle specific, if calf IMAT is different between a healthy obese group (HO), a group with diabetes mellitus (D), and a group with diabetes mellitus and peripheral neuropathy (DN), and if IMAT volume or the ratio of IMAT/muscle volume is related to physical function in these groups. Methods. 10 healthy obese people, 11 with type 2 diabetes, 24 with diabetes and peripheral neuropathy, had assessments of muscle morphology, physical function and muscle performance. Results. The gastrocnemius muscle had a higher ratio of IMAT/muscle volume than any other muscle or compartment. There were no differences between groups in calf muscle or IMAT volumes. Calf IMAT was inversely related to physical performance on the 6-minute walk test (r = -0.47) and physical performance test (r = -0.36). IMAT/muscle volume was inversely related to physical performance (PPT, r = -0.44; 6 MW r = 0.48; stair power, r = -0.30). Conclusions. IMAT accumulation varies in calf muscles, is highest in the gastrocnemius muscle, and is associated with poor physical performance. PMID- 22666592 TI - Cytoplasmic and nuclear localization of TCTP in normal and cancer cells. AB - Objective. Intracellular localization of translationally controlled tumour protein (TCTP) was investigated in cancer cells. Methods. The expression and localization of TCTP were detected at 12 h, 24 h, 48 h, 60 h time points in culture of human hepatocarcinoma cell line HepG2, human cervical carcinoma cell line HeLa, and human normal liver cell line HL-7702 by immunofluorescence. Results. TCTP was expressed in both normal and tumor cells, and its localization changes at different time points. TCTP was mainly expressed in cytoplasm from 24 h to 48 h then expressed in both nucleus and cytoplasm at 60 h in HL-7702 cells. While in HepG2 cells, TCTP first localized at cell membrane within 24 h then at both nucleus and cytoplasm from 48 h to 60 h; TCTP localized at both nucleus and cytoplasm from 12 h to 60 h in Hela cells. Conclusion. The translocation of intracellular expression of TCTP in normal and tumor cells at different time points may pave a path to the studying of TCTP role in tumor growth. PMID- 22666593 TI - In search of novel targets for heart disease: myocardin and myocardin-related transcriptional cofactors. AB - Growing evidence suggests that gene-regulatory networks, which are responsible for directing cardiovascular development, are altered under stress conditions in the adult heart. The cardiac gene regulatory network is controlled by cardioenriched transcription factors and multiple-cell-signaling inputs. Transcriptional coactivators also participate in gene-regulatory circuits as the primary targets of both physiological and pathological signals. Here, we focus on the recently discovered myocardin-(MYOCD) related family of transcriptional cofactors (MRTF-A and MRTF-B) which associate with the serum response transcription factor and activate the expression of a variety of target genes involved in cardiac growth and adaptation to stress via overlapping but distinct mechanisms. We discuss the involvement of MYOCD, MRTF-A, and MRTF-B in the development of cardiac dysfunction and to what extent modulation of the expression of these factors in vivo can correlate with cardiac disease outcomes. A close examination of the findings identifies the MYOCD-related transcriptional cofactors as putative therapeutic targets to improve cardiac function in heart failure conditions through distinct context-dependent mechanisms. Nevertheless, we are in support of further research to better understand the precise role of individual MYOCD-related factors in cardiac function and disease, before any therapeutic intervention is to be entertained in preclinical trials. PMID- 22666594 TI - Adrenocortical and adipose responses to high-altitude-induced, long-term hypoxia in the ovine fetus. AB - By late gestation, the maturing hypothalamo-pituitary-adrenal (HPA) axis aids the fetus in responding to stress. Hypoxia represents a significant threat to the fetus accompanying situations such as preeclampsia, smoking, high altitude, and preterm labor. We developed a model of high-altitude (3,820 m), long-term hypoxia (LTH) in pregnant sheep. We describe the impact of LTH on the fetal HPA axis at the level of the hypothalamic paraventricular nucleus (PVN), anterior pituitary corticotrope, and adrenal cortex. At the PVN and anterior pituitary, the responses to LTH are consistent with hypoxia being a potent activator of the HPA axis and potentially maladaptive, while the adrenocortical response to LTH appears to be primarily adaptive. We discuss mechanisms involved in the delicate balance between these seemingly opposing responses that preserve the normal ontogenic rise in fetal plasma cortisol essential for organ maturation and in this species, birth. Further, we examine the response to, and ramifications of, an acute secondary stressor in the LTH fetus. We provide an integrative model on the potential role of adipose in modulating these responses to LTH. Integration of these adaptive responses to LTH plays a key role in promoting normal fetal growth and development under conditions of a chronic stress. PMID- 22666596 TI - Injuries, sequelae, and treatment of lightning-induced injuries: 10 years of experience at a swiss trauma center. AB - Principals. Lightning is one of the most powerful and spectacular natural phenomena. Lightning strikes to humans are uncommon but can cause devastating injuries. We analyzed lightning-related admissions to our emergency department from January 2000 to December 2010 to review and highlight the main features of lightning-related injuries. Methods. All data were collected prospectively and entered in the emergency department' database (Qualicare Switzerland) and retrospectively analyzed. Results. Nine patients with lightning-related injuries presented to our emergency department. Four were female, and five were male. The most common site of injury was the nervous system (6 out of 9 patients) followed by the cardiovascular system (5 out of 9 patients). The third most common injuries occurred to the skin (3 out of 9 patients). Four of the patients had to be hospitalized for further observation. Conclusion. Reports of lightning strikes and related injuries are scarce. The establishment of an international register would therefore benefit the understanding of their injury patterns and facilitate specific treatment. PMID- 22666595 TI - Assessments of arterial stiffness and endothelial function using pulse wave analysis. AB - Conventionally, the assessments of endothelial function and arterial stiffness require different sets of equipment, making the inclusion of both tests impractical for clinical and epidemiological studies. Pulse wave analysis (PWA) provides useful information regarding the mechanical properties of the arterial tree and can also be used to assess endothelial function. PWA is a simple, valid, reliable, and inexpensive technique, offering great clinical and epidemiological potential. The current paper will outline how to measure arterial stiffness and endothelial function using this technique and include discussion of validity and reliability. PMID- 22666597 TI - Emergency Department Discharge Instructions: Lessons Learned through Developing New Patient Education Materials. AB - Our multidisciplinary team developed a new set of discharge instructions for five common emergency department diagnoses using recommended tools for creating literacy-appropriate and patient-centered education materials. We found that the recommended tools for document creation were essential in constructing the new instructions. However, while the tools were necessary, they were not sufficient. This paper describes the insights gained and lessons learned in this document creation process. PMID- 22666598 TI - Cognitive remediation for individuals with psychosis in a supported education setting: a pilot study. AB - Cognitive remediation (CR) is a treatment approach that is being increasingly examined as a means through which the cognitive impacts of schizophrenia might be ameliorated. While CR has demonstrated good outcomes when paired with supported employment, little is known regarding how it might be integrated within supported education contexts. In this study CR was examined in a supported education context with 16 individuals with psychosis. The findings indicated that CR aligned well with the academic curriculum with very low attrition, was found useful by students, and showed similar pre-post differences on cognitive measures as those found in previous work. PMID- 22666599 TI - Kinetic chain rehabilitation: a theoretical framework. AB - Sequenced physiologic muscle activations in the upper and lower extremity result in an integrated biomechanical task. This sequencing is known as the kinetic chain, and, in upper extremity dominant tasks, the energy development and output follows a proximal to distal sequencing. Impairment of one or more kinetic chain links can create dysfunctional biomechanical output leading to pain and/or injury. When deficits exist in the preceding links, they can negatively affect the shoulder. Rehabilitation of shoulder injuries should involve evaluation for and restoration of all kinetic chain deficits that may hinder kinetic chain function. Rehabilitation programs focused on eliminating kinetic chain deficits, and soreness should follow a proximal to distal rationale where lower extremity impairments are addressed in addition to the upper extremity impairments. A logical progression focusing on flexibility, strength, proprioception, and endurance with kinetic chain influence is recommended. PMID- 22666600 TI - Protectors or Traitors: The Roles of PON2 and PON3 in Atherosclerosis and Cancer. AB - Cancer and atherosclerosis are major causes of death in western societies. Deregulated cell death is common to both diseases, with significant contribution of inflammatory processes and oxidative stress. These two form a vicious cycle and regulate cell death pathways in either direction. This raises interest in antioxidative systems. The human enzymes paraoxonase-2 (PON2) and PON3 are intracellular enzymes with established antioxidative effects and protective functions against atherosclerosis. Underlying molecular mechanisms, however, remained elusive until recently. Novel findings revealed that both enzymes locate to mitochondrial membranes where they interact with coenzyme Q10 and diminish oxidative stress. As a result, ROS-triggered mitochondrial apoptosis and cell death are reduced. From a cardiovascular standpoint, this is beneficial given that enhanced loss of vascular cells and macrophage death forms the basis for atherosclerotic plaque development. However, the same function has now been shown to raise chemotherapeutic resistance in several cancer cells. Intriguingly, PON2 as well as PON3 are frequently found upregulated in tumor samples. Here we review studies reporting PON2/PON3 deregulations in cancer, summarize most recent findings on their anti-oxidative and antiapoptotic mechanisms, and discuss how this could be used in putative future therapies to target atherosclerosis and cancer. PMID- 22666602 TI - Expression of neutral endopeptidase, endothelin-1, and nuclear factor kappa B in prostate cancer: interrelations and associations with prostate-specific antigen recurrence after radical prostatectomy. AB - Objective. To study the impact of the neutral endopeptidase (NEP)/neuropeptides (NPs) axis and nuclear factor kappa B (NFkappaB) as predictors of prostate specific antigen (PSA) recurrence after radical prostatectomy (RP). Patients and Methods. 70 patients with early-stage PC were treated with RP and their tumor samples were evaluated for expression of NEP, endothelin-1 (ET-1) and NFkappaB (p65). Time to PSA recurrence was correlated with the examined parameters and combined with preoperative PSA level, Gleason score, pathological TNM (pT) stage, and surgical margin (SM) assessment. Results and Limitations. Membranous expression of NEP (P < 0.001), cytoplasmic ET-1 (P = 0.002), and cytoplasmic NFkappaB (P < 0.001) were correlated with time to PSA relapse. NEP was associated with ET-1 (P < 0.001) and NFkappaB (P < 0.001). ET-1 was also correlated with NFkappaB (P < 0.001). NEP expression (P = 0.017), pT stage (P = 0.013), and SMs (P = 0.036) were independent predictors of time to PSA recurrence. Conclusions. There seems to be a clinical model of NEP/NPs and NFkappaB pathways interconnection, with their constituents following inverse patterns of expression in accordance with their biological roles and molecular interrelations. PMID- 22666601 TI - Markers of field cancerization: proposed clinical applications in prostate biopsies. AB - Field cancerization denotes the occurrence of genetic, epigenetic, and biochemical aberrations in structurally intact cells in histologically normal tissues adjacent to cancerous lesions. This paper tabulates markers of prostate field cancerization known to date and discusses their potential clinical value in the analysis of prostate biopsies, including diagnosis, monitoring progression during active surveillance, and assessing efficacy of presurgical neoadjuvant and focal therapeutic interventions. PMID- 22666604 TI - Pathophysiology of portal hypertension and esophageal varices. AB - Esophageal varices are the major complication of portal hypertension. It is detected in about 50% of cirrhosis patients, and approximately 5-15% of cirrhosis patients show newly formed varices or worsening of varices each year. The major therapeutic strategy of esophageal varices consists of primary prevention, treatment for bleeding varices, and secondary prevention, which are provided by pharmacological, endoscopic, interventional and surgical treatments. Optimal management of esophageal varices requires a clear understanding of the pathophysiology and natural history. In this paper, we outline the current knowledge and future prospect in the pathophysiology of esophageal varices and portal hypertension. PMID- 22666603 TI - The Link between Hypersensitivity Syndrome Reaction Development and Human Herpes Virus-6 Reactivation. AB - Background. There are challenges in the clinical diagnosis of drug-induced injury and in obtaining information on the reactivation of human herpes viruses (HHV) during idiosyncratic adverse drug reactions. Objectives. (i) To develop a unified list of drugs incriminated in drug-induced hepatotoxicity and severe cutaneous reactions, in which drug hypersensitivity leads to HHV-6 reactivation and further complication of therapy and recovery and (ii) to supplement the already available data on reporting frequencies of liver- or skin-induced cases with knowledge of individual case reports, including HHV-6 reactivation and briefly introducing chromosomally integrated HHV-6. Data Sources and Extraction. Drugs identified as causes of (i) idiosyncratic reactions, (ii) drug-induced hypersensitivity, drug induced hepatotoxicity, acute liver failure, and Stevens-Johnson syndrome, and (iii) human herpes virus reactivation in PubMed since 1997 have been collected and discussed. Results. Data presented in this paper show that HHV-6 reactivation is associated with more severe organ involvement and a prolonged course of disease. Conclusion. This analysis of HHV-6 reactivation associated with drug induced severe cutaneous reactions and hepatotoxicity will aid in causality assessment and clinical diagnosis of possible life-threatening events and will provide a basis for further patient characterization and therapy. PMID- 22666605 TI - An orthopedic-, surgical-, and epidemiological-based investigation of leprosy, in the Tamil Nadu state of India. AB - No other research paper has ever been written about leprosy in this manner. The orthopedic and surgical implications, as well as the functional debility caused by the disease, have not been previously explained by past research as they have in such a comprehensive manner in this paper. The results of this study have regional and global implications as they pertain to disease pathology, risk factor recognition/disease prevention, and treatment. This paper is a unique, in that it also serves as a combination of a review of the current medical literature, as well as an epidemiological survey of the disease in a region of the world which has never been researched in the past. Clinical data points to the possibility of a new strain of the disease. This information is of significance because it effects prevention and improved treatment of the disease, which leads to devastating sequela. This was a cross-sectional study involving subjects diagnosed with leprosy in the Chengalpet region of the Kancheepuram District, of the Tamil Nadu state of India. The study was performed at the Tamil Nadu Medical College Teaching Hospital and Research Center. This study included various physical examinations, observation and survey of lesions, questionnaires in regard the debilitating orthopedic and medical effects of the disease, as well as treatment options. PMID- 22666606 TI - Measurement of intervertebral motion using quantitative fluoroscopy: report of an international forum and proposal for use in the assessment of degenerative disc disease in the lumbar spine. AB - Quantitative fluoroscopy (QF) is an emerging technology for measuring intervertebral motion patterns to investigate problem back pain and degenerative disc disease. This International Forum was a networking event of three research groups (UK, US, Hong Kong), over three days in San Francisco in August 2009. Its aim was to reach a consensus on how best to record, analyse, and communicate QF information for research and clinical purposes. The Forum recommended that images should be acquired during regular trunk motion that is controlled for velocity and range, in order to minimise externally imposed variability as well as to correlate intervertebral motion with trunk motion. This should be done in both the recumbent passive and weight bearing active patient configurations. The main recommended outputs from QF were the true ranges of intervertebral rotation and translation, neutral zone laxity and the consistency of shape of the motion patterns. The main clinical research priority should initially be to investigate the possibility of mechanical subgroups of patients with chronic, nonspecific low back pain by comparing their intervertebral motion patterns with those of matched healthy controls. PMID- 22666607 TI - VEGF is involved in the increase of dermal microvascular permeability induced by tryptase. AB - Tryptases are predominantly mast cell-specific serine proteases with pleiotropic biological activities and play a critical role in skin allergic reactions, which are manifested with rapid edema and increases of vascular permeability. The exact mechanisms of mast cell tryptase promoting vascular permeability, however, are unclear and, therefore, we investigated the effect and mechanism of tryptase or human mast cells (HMC-1) supernatant on the permeability of human dermal microvascular endothelial cells (HDMECs). Both tryptase and HMC-1 supernatant increased permeability of HDMECs significantly, which was resisted by tryptase inhibitor APC366 and partially reversed by anti-VEGF antibody and SU5614 (catalytic inhibitor of VEGFR). Furthermore, addition of tryptase to HDMECs caused a significant increase of mRNA and protein levels of VEGF and its receptors (Flt-1 and Flk-1) by Real-time RT-PCR and Western blot, respectively. These results strongly suggest an important role of VEGF on the permeability enhancement induced by tryptase, which may lead to novel means of controlling allergic reaction in skin. PMID- 22666608 TI - Clinical and Immunopathologic Profile of Mexican Patients with IgG4 Autoimmune Pancreatitis. AB - Autoimmune pancreatitis is part of the spectrum of IgG4-associated diseases. Its diagnostic criteria and histological subtypes have been formally proposed recently and although based on current data it has been suggested that there are differences in clinical presentation among populations, more research is needed to properly establish if this heterogeneity exists. In this paper, we describe 15 cases of autoimmune pancreatitis diagnosed at a Mexican centre of reference, all of them associated to the lymphoplasmocytic sclerosing pancreatitis variant. The mean age at the onset of symptoms was 47.5 +/- 14.4 years, and 53% of patients were male. The main manifestations were weight loss (87%), obstructive jaundice (53%), and acute (27%) and chronic (27%) pancreatitis. Only 20% of patients had high IgG4 serum levels at the time of diagnosis. All patients receiving prednisone responded favourably, both in their pancreatic and extrapancreatic manifestations. Clinical manifestations of Mexican patients showed certain differences with respect to those usually reported. PMID- 22666610 TI - Gefitinib in Combination with Weekly Docetaxel in Patients with Metastatic Breast Cancer Caused Unexpected Toxicity: Results from a Randomized Phase II Clinical Trial. AB - In patients with metastatic breast cancer, taxane treatment demonstrates activity but is not curative. Targeted treatment modalities are therefore necessary in order to improve outcomes in this group. A randomized placebo-controlled phase II trial was initiated to evaluate effect and toxicity of gefitinib (250 mg QD) and docetaxel 35 mg/m(2) (six of seven weeks) (NCT 00319618). The inclusion of 66 patients was planned. The study was closed due to treatment-related toxicity. Of the 18 included patients, seven (of which three received gefitinib) were withdrawn from the study due to toxicity. Of the nine patients receiving gefitinib and chemotherapy, one achieved a partial response and four stable disease. In the chemotherapy of nine patients, four had a partial response and four stable disease. The breast cancer patients in this study were genotyped using a panel of 14 single-nucleotide polymorphisms (SNPs), previously found associated with docetaxel clearance in a cohort of lung cancer patients. We were unable to identify genes related to toxicity in this study. Nevertheless, toxicity was aggravated by the addition of the tyrosine kinase inhibitor. In conclusion, despite adequately tolerated as monotherapy, combination regimens should be carefully considered for overlapping adverse events in order to avoid increased treatment-related toxicity. PMID- 22666609 TI - Minimally invasive surgical therapies for atrial fibrillation. AB - Atrial fibrillation is the most common sustained arrhythmia and is associated with significant risks of thromboembolism, stroke, congestive heart failure, and death. There have been major advances in the management of atrial fibrillation including pharmacologic therapies, antithrombotic therapies, and ablation techniques. Surgery for atrial fibrillation, including both concomitant and stand alone interventions, is an effective therapy to restore sinus rhythm. Minimally invasive surgical ablation is an emerging field that aims for the superior results of the traditional Cox-Maze procedure through a less invasive operation with lower morbidity, quicker recovery, and improved patient satisfaction. These novel techniques utilize endoscopic or minithoracotomy approaches with various energy sources to achieve electrical isolation of the pulmonary veins in addition to other ablation lines. We review advancements in minimally invasive techniques for atrial fibrillation surgery, including management of the left atrial appendage. PMID- 22666611 TI - Sentinel Lymph Node Biopsy in Pure DCIS: Is It Necessary? AB - Introduction. Sentinel lymph node biopsy (SLNB) in patients with pure ductal carcinoma in situ (DCIS) has been a matter of debate due to very low rate of axillary metastases. We therefore aimed to identify factors in a single institutional series to select patients who may benefit from SLNB. Material and Methods. Patients, diagnosed with pure DCIS (n = 63) between July 2000 and March 2011, were reviewed. All the sentinel lymph nodes were examined by serial sectioning (50 MUm) of the entire lymph node and H&E staining, and by cytokeratin immunostaining in suspicious cases. Results. Median age was 51 (range, 30-79). Of 63 patients, 40 cases (63.5%) with pure DCIS underwent SLN, and 2 of them had a positive SLN (5%). In both 2 cases with SLN metastases, only one sentinel lymph node was involved with tumor cells. Patients who underwent SLNB were more likely to have a tumor size >30 mm or DCIS with intermediate and high nuclear grade or a mastectomy in univariate and multivariate analyses. Conclusion. In our series, we found a slightly higher rate of SLNB positivity in patients with pure DCIS than the large series reported elsewhere. This may either be due to the meticulous examination of SLNs by serial sectioning technique or due to our patient selection criteria or both. PMID- 22666613 TI - Endodontic management of mandibular first molar with middle distal canal: a case report. AB - The knowledge of variations in root canal morphology is critical for a successful endodontic treatment. This article presents the endodontic management of a unique case of mandibular molar with middle distal canal which is quite uncommon. PMID- 22666614 TI - Successful management of a gastric sleeve leak with an endoscopic stent. AB - Laparoscopic sleeve gastrectomy has been a recently developed technique for treating morbid obesity. Gagner and Patterson performed the first laparoscopic sleeve gastrectomy as part of a duodenal switch procedure at Mount Sinai Hospital in New York in 1999. Since then many surgeons and institutions have adopted this technique. One of the most dreaded complications of sleeve gastrectomy is a leak along the staple line. We present the case of a 23-year-old female with gastric sleeve leak managed successfully with a fully covered wall flex stent. Our aim is to examine the incidence, causes, classification, and presentation of gastric sleeve leaks and to evaluate the use of endoscopic stents in its management. PMID- 22666612 TI - Plasticity-inducing TMS protocols to investigate somatosensory control of hand function. AB - Hand function depends on sensory feedback to direct an appropriate motor response. There is clear evidence that somatosensory cortices modulate motor behaviour and physiology within primary motor cortex. However, this information is mainly from research in animals and the bridge to human hand control is needed. Emerging evidence in humans supports the notion that somatosensory cortices modulate motor behaviour, physiology and sensory perception. Transcranial magnetic stimulation (TMS) allows for the investigation of primary and higher-order somatosensory cortices and their role in control of hand movement in humans. This review provides a summary of several TMS protocols in the investigation of hand control via the somatosensory cortices. TMS plasticity inducing protocols reviewed include paired associative stimulation, repetitive TMS, theta-burst stimulation as well as other techniques that aim to modulate cortical excitability in sensorimotor cortices. Although the discussed techniques may modulate cortical excitability, careful consideration of experimental design is needed to isolate factors that may interfere with desired results of the plasticity-inducing protocol, specifically events that may lead to metaplasticity within the targeted cortex. PMID- 22666615 TI - The onset of a peripheral ameloblastoma. AB - Incipient odontogenic tumors often display intermediate features between two or more lesions leading to diagnosis dilemma. We report the onset of a peripheral ameloblastoma fortuitously found subjacent to a nondysplastic leukoplakia in the region of missing 38 teeth of a 52-year-old man. The aim of this paper is the discussion of the microscopical features observed in the case reported which allowed the establishment of the final diagnosis of an early peripheral ameloblastoma. PMID- 22666616 TI - An aggressive sphenoid wing meningioma causing foster kennedy syndrome. AB - Foster Kennedy syndrome is a rare neurological condition with ophthalmic significance that can manifest as acute visual loss. It is classically characterised by unilateral optic nerve atrophy and contralateral papilledema resulting from an intracranial neoplasm. Physicians should consider Foster Kennedy syndrome in patients who present with visual loss and who have a history of intracranial neoplasm. In addition to ophthalmologic examination, neuroimaging is essential for the diagnosis of Foster Kennedy syndrome. PMID- 22666617 TI - Conjunctival lymphangioma: a case report and brief review of the literature. AB - Background. Lymphangioma is a rare venolymphatic lesion, characterized by dilation of lymphatic vessels. It may occur as an isolated lesion or, more often, represent the surface component of a deep orbital lymphangioma. Case. We report a case of a conjunctival lymphangioma on a 58-year-old male that had simultaneously an upper respiratory tract infection. Excision and biopsy confirmed the nature of the lesion, and there has been no relapse to date. Conclusion. Conjunctival lymphangioma is a rare condition in which the diagnose, must be kept in mind in patients with a red eye resistance to topical therapy and in association with an upper respiratory tract infection. Finally, it is also necessary to be aware of possible recurrence of the lesion. PMID- 22666618 TI - Non-pharmacological therapy for atrial fibrillation: managing the left atrial appendage. AB - The prevalence of atrial fibrillation (AF) is increasing in parallel with an ageing population leading to increased morbidity and mortality. The most feared complication of AF is stroke, with the arrhythmia being responsible for up to 20% of all ischemic strokes. An important contributor to this increased risk of stroke is the left atrial appendage (LAA). A combination of the LAA's unique geometry and atrial fibrillation leads to low blood flow velocity and stasis, which are precursors to thrombus formation. It has been hypothesized for over half a century that excision of the LAA would lead to a reduction in the incidence of stroke. It has only been in the last 20-25 years that the knowledge and technology has been available to safely carry out such a procedure. We now have a number of viable techniques, both surgical and percutaneous, which will be covered in this paper. PMID- 22666619 TI - Insulin receptor expression and activity in the brains of nondiabetic sporadic Alzheimer's disease cases. AB - We investigated the contents of the insulin receptor-beta subunit (IRbeta) and [Tyr1162/1163]-phosphorylated IRbeta as surrogate indices of total IR content and IR activation in postmortem hippocampal formation brain specimens from nondiabetic sporadic Alzheimer's disease (AD) cases. We found no significant changes in the brain contents of total IRbeta or [Tyr1162/1163]-phosphorylated IRbeta, suggesting normal IR content and activation in the brains of nondiabetic sporadic AD cases. Moreover, total IRbeta and [Tyr1162/1163]-phosphorylated IRbeta levels in the hippocampal formation are not correlated with the severity of amyloid or tau-neuropathology. Exploring the regulation of glycogen synthase kinase 3 (GSK3) alpha/beta, key IR-signaling components, we observed significantly lower levels of total GSK3 alpha/beta in brain specimens from nondiabetic AD cases, suggesting that impaired IR signaling mechanisms might contribute to the onset and/or progression of AD dementia. Outcomes from our study support the development of insulin-sensitizing therapeutic strategies to stimulate downstream IR signaling in nondiabetic AD cases. PMID- 22666620 TI - Alterations in Lipid Levels of Mitochondrial Membranes Induced by Amyloid-beta: A Protective Role of Melatonin. AB - Alzheimer pathogenesis involves mitochondrial dysfunction, which is closely related to amyloid-beta (Abeta) generation, abnormal tau phosphorylation, oxidative stress, and apoptosis. Alterations in membranal components, including cholesterol and fatty acids, their characteristics, disposition, and distribution along the membranes, have been studied as evidence of cell membrane alterations in AD brain. The majority of these studies have been focused on the cytoplasmic membrane; meanwhile the mitochondrial membranes have been less explored. In this work, we studied lipids and mitochondrial membranes in vivo, following intracerebral injection of fibrillar amyloid-beta (Abeta). The purpose was to determine how Abeta may be responsible for beginning of a vicious cycle where oxidative stress and alterations in cholesterol, lipids and fatty acids, feed back on each other to cause mitochondrial dysfunction. We observed changes in mitochondrial membrane lipids, and fatty acids, following intracerebral injection of fibrillar Abeta in aged Wistar rats. Melatonin, a well-known antioxidant and neuroimmunomodulator indoleamine, reversed some of these alterations and protected mitochondrial membranes from obvious damage. Additionally, melatonin increased the levels of linolenic and n-3 eicosapentaenoic acid, in the same site where amyloid beta was injected, favoring an endogenous anti-inflammatory pathway. PMID- 22666621 TI - Microglial scavenger receptors and their roles in the pathogenesis of Alzheimer's disease. AB - Alzheimer's disease (AD) is increasing in prevalence with the aging population. Deposition of amyloid-beta (Abeta) in the brain of AD patients is a hallmark of the disease and is associated with increased microglial numbers and activation state. The interaction of microglia with Abeta appears to play a dichotomous role in AD pathogenesis. On one hand, microglia can phagocytose and clear Abeta, but binding of microglia to Abeta also increases their ability to produce inflammatory cytokines, chemokines, and neurotoxic reactive oxygen species (ROS). Scavenger receptors, a group of evolutionally conserved proteins expressed on the surface of microglia act as receptors for Abeta. Of particular interest are SCARA 1 (scavenger receptor A-1), CD36, and RAGE (receptor for advanced glycation end products). SCARA-1 appears to be involved in the clearance of Abeta, while CD36 and RAGE are involved in activation of microglia by Abeta. In this review, we discuss the roles of various scavenger receptors in the interaction of microglia with Abeta and propose that these receptors play complementary, nonredundant functions in the development of AD pathology. We also discuss potential therapeutic applications for these receptors in AD. PMID- 22666622 TI - Traumatic brain injury, microglia, and Beta amyloid. AB - Recently, there has been growing interest in the association between traumatic brain injury (TBI) and Alzheimer's Disease (AD). TBI and AD share many pathologic features including chronic inflammation and the accumulation of beta amyloid (Abeta). Data from both AD and TBI studies suggest that microglia play a central role in Abeta accumulation after TBI. This paper focuses on the current research on the role of microglia response to Abeta after TBI. PMID- 22666623 TI - Ocular manifestations of Alzheimer's disease in animal models. AB - Alzheimer's disease (AD) is the most common form of dementia, and the pathological changes of senile plaques (SPs) and neurofibrillary tangles (NFTs) in AD brains are well described. Clinically, a diagnosis remains a postmortem one, hampering both accurate and early diagnosis as well as research into potential new treatments. Visual deficits have long been noted in AD patients, and it is becoming increasingly apparent that histopathological changes already noted in the brain also occur in an extension of the brain; the retina. Due to the optically transparent nature of the eye, it is possible to image the retina at a cellular level noninvasively and thus potentially allow an earlier diagnosis as well as a way of monitoring progression and treatment effects. Transgenic animal models expressing amyloid precursor protein (APP) presenilin (PS) and tau mutations have been used successfully to recapitulate the pathological findings of AD in the brain. This paper will cover the ocular abnormalities that have been detected in these transgenic AD animal models. PMID- 22666625 TI - More than meets the eye: functionally salient changes in internal bone architecture accompany divergence in cichlid feeding mode. AB - African cichlids have undergone extensive and repeated adaptive radiations in foraging habitat. While the external morphology of the cichlid craniofacial skeleton has been studied extensively, biomechanically relevant changes to internal bone architecture have been largely overlooked. Here we explore two fundamental questions: (1) Do changes in the internal architecture of bone accompany shifts in foraging mode? (2) What is the genetic basis for this trait? We focus on the maxilla, which is an integral part of the feeding apparatus and an element that should be subjected to significant bending forces during biting. Analyses of MUCT scans revealed clear differences between the maxilla of two species that employ alternative foraging strategies (i.e., biting versus suction feeding). Hybrids between the two species exhibit maxillary geometries that closely resemble those of the suction feeding species, consistent with a dominant mode of inheritance. This was supported by the results of a genetic mapping experiment, where suction feeding alleles were dominant to biting alleles at two loci that affect bone architecture. Overall, these data suggest that the internal structure of the cichlid maxilla has a tractable genetic basis and that discrete shifts in this trait have accompanied the evolution of alternate feeding modes. PMID- 22666624 TI - Sweepers in the CNS: Microglial Migration and Phagocytosis in the Alzheimer Disease Pathogenesis. AB - Microglia are multifunctional immune cells in the central nervous system (CNS). In the neurodegenerative diseases such as Alzheimer's disease (AD), accumulation of glial cells, gliosis, occurs in the lesions. The role of accumulated microglia in the pathophysiology of AD is still controversial. When neuronal damage occurs, microglia exert diversified functions, including migration, phagocytosis, and production of various cytokines and chemokines. Among these, microglial phagocytosis of unwanted neuronal debris is critical to maintain the healthy neuronal networks. Microglia express many surface receptors implicated in phagocytosis. It has been suggested that the lack of microglial phagocytosis worsens pathology of AD and induces memory impairment. The present paper summarizes recent evidences on implication of microglial chemotaxis and phagocytosis in AD pathology and discusses the mechanisms related to chemotaxis toward injured neurons and phagocytosis of unnecessary debris. PMID- 22666626 TI - A Short-Term Advantage for Syngamy in the Origin of Eukaryotic Sex: Effects of Cell Fusion on Cell Cycle Duration and Other Effects Related to the Duration of the Cell Cycle-Relationship between Cell Growth Curve and the Optimal Size of the Species, and Circadian Cell Cycle in Photosynthetic Unicellular Organisms. AB - The origin of sex is becoming a vexatious issue for Evolutionary Biology. Numerous hypotheses have been proposed, based on the genetic effects of sex, on trophic effects or on the formation of cysts and syncytia. Our approach addresses the change in cell cycle duration which would cause cell fusion. Several results are obtained through graphical and mathematical analysis and computer simulations. (1) In poor environments, cell fusion would be an advantageous strategy, as fusion between cells of different size shortens the cycle of the smaller cell (relative to the asexual cycle), and the majority of mergers would occur between cells of different sizes. (2) The easiest-to-evolve regulation of cell proliferation (sexual/asexual) would be by modifying the checkpoints of the cell cycle. (3) A regulation of this kind would have required the existence of the G2 phase, and sex could thus be the cause of the appearance of this phase. Regarding cell cycle, (4) the exponential curve is the only cell growth curve that has no effect on the optimal cell size in unicellular species; (5) the existence of a plateau with no growth at the end of the cell cycle explains the circadian cell cycle observed in unicellular algae. PMID- 22666627 TI - Patterns of Cell Activity in the Subthalamic Region Associated with the Neuroprotective Action of Near-Infrared Light Treatment in MPTP-Treated Mice. AB - We have shown previously that near-infrared light (NIr) treatment or photobiomodulation neuroprotects dopaminergic cells in substantia nigra pars compacta (SNc) from degeneration induced by 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) in mice. The present study explores whether NIr treatment changes the patterns of Fos expression in the subthalamic region, namely, the subthalamic nucleus (STN) and zona incerta (ZI); both cell groups have abnormally overactive cells in parkinsonian cases. BALB/c mice were treated with MPTP (100-250 mg/kg) or saline either over 30 hours followed by either a two hour or six-day survival period (acute model) or over five weeks followed by a three-week survival period (chronic model). NIr and MPTP were applied simultaneously. Brains were processed for Fos immunochemistry, and cell number was estimated using stereology. Our major finding was that NIr treatment reduced (30-45%) the increase in Fos(+) cell number evident in the STN and ZI after MPTP insult. This reduction was concurrent with the neuroprotection of dopaminergic SNc cells shown previously and was evident in both MPTP models (except for the 2 hours survival period which showed no changes in cell number). In summary, our results indicated that NIr had long lasting effects on the activity of cells located deep in the brain and had repaired partially the abnormal activity generated by the parkinsonian toxin. PMID- 22666628 TI - Corticostriatal Plastic Changes in Experimental L-DOPA-Induced Dyskinesia. AB - In Parkinson's disease (PD), alteration of dopamine- (DA-) dependent striatal functions and pulsatile stimulation of DA receptors caused by the discontinuous administration of levodopa (L-DOPA) lead to a complex cascade of events affecting the postsynaptic striatal neurons that might account for the appearance of L-DOPA induced dyskinesia (LID). Experimental models of LID have been widely used and extensively characterized in rodents and electrophysiological studies provided remarkable insights into the inner mechanisms underlying L-DOPA-induced corticostriatal plastic changes. Here we provide an overview of recent findings that represent a further step into the comprehension of mechanisms underlying maladaptive changes of basal ganglia functions in response to L-DOPA and associated to development of LID. PMID- 22666629 TI - A possible novel anti-inflammatory mechanism for the pharmacological prolyl hydroxylase inhibitor 3,4-dihydroxybenzoate: implications for use as a therapeutic for Parkinson's disease. AB - Parkinson's disease (PD) is an age-related neurodegenerative disorder characterized in part by the preferential loss of nigrostriatal dopaminergic neurons. Although the precise etiology of PD is unknown, accumulating evidence suggests that PD involves microglial activation that exerts neurotoxic effects through production of proinflammatory cytokines and increased oxidative and nitrosative stress. Thus, controlling microglial activation has been suggested as a therapeutic target for combating PD. Previously we demonstrated that pharmacological inhibition of a class of enzymes known as prolyl hydroxylases via 3,4-dihydroxybenzoate administration protected against MPTP-induced neurotoxicity, however the exact mechanisms involved were not elucidated. Here we show that this may be due to DHB's ability to inhibit microglial activation. DHB significantly attenuated LPS-mediated induction of nitric oxide synthase and pro inflammatory cytokines in murine BV2 microglial cells in vitro in conjunction with reduced ROS production and activation of NFkappaB and MAPK pathways possibly due to up-regulation of HO-1 levels. HO-1 inhibition partially abrogates LPS mediated NFkappaB activity and subsequent NO induction. In vivo, DHB pre treatment suppresses microglial activation elicited by MPTP treatment. Our results suggest that DHB's neuroprotective properties could be due to its ability to dampen induction of microglial activation via induction of HO-1. PMID- 22666631 TI - The prevalence of fatigue following deep brain stimulation surgery in Parkinson's disease and association with quality of life. AB - Fatigue is a common and disabling nonmotor symptom seen in Parkinson's disease (PD). While deep brain stimulation surgery (DBS) improves motor symptoms, it has also been associated with non-motor side effects. To date no study has utilized standardized instruments to evaluate fatigue following DBS surgery. Our objective was to determine the prevalence of fatigue following DBS surgery in PD its impact on quality of life and explore predictive factors. We recruited 44 PD subjects. At least one year following DBS placement, we administered the Fatigue Severity Scale (FSS), the Parkinson's Disease Questionnaire (PDQ-39), the Beck Depression Inventory, the Beck Anxiety Inventory, the UPDRS, and a neuropsychological battery. Fifty-eight percent of subjects had moderate to severe fatigue. Fatigue was significantly associated with quality of life, depression, and anxiety. Depression preoperatively was the only predictive factor of fatigue. Fatigue is common following DBS surgery and significantly impacts quality of life. PMID- 22666630 TI - The emerging role of proteolysis in mitochondrial quality control and the etiology of Parkinson's disease. AB - Mitochondria are highly dynamic organelles that are important for many diverse cellular processes, such as energy metabolism, calcium buffering, and apoptosis. Mitochondrial biology and dysfunction have recently been linked to different types of cancers and neurodegenerative diseases, most notably Parkinson's disease. Thus, a better understanding of the quality control systems that maintain a healthy mitochondrial network can facilitate the development of effective treatments for these diseases. In this perspective, we will discuss recent advances on two mitochondrial quality control pathways: the UPS and mitophagy, highlight how new players may be contributing to regulate these pathways. We believe the proteases involved will be key and novel regulators of mitochondrial quality control, and this knowledge will provide insights into future studies aimed to combat neurodegenerative diseases. PMID- 22666632 TI - Molecular mechanisms of liver injury and hepatocarcinogenesis: focusing on the role of stress-activated MAPK. AB - Hepatocellular carcinoma (HCC) is the third most common cause of cancer mortality. Short-term prognosis of patients with HCC has improved recently due to advances in early diagnosis and treatment, but long-term prognosis is still unsatisfactory. Therefore, obtaining a further understanding of the molecular carcinogenic mechanisms and the unique pathogenic biology of HCC is important. The most characteristic process in hepatocarcinogenesis is underlying chronic liver injury, which leads to repeated cycles of hepatocyte death, inflammation, and compensatory proliferation and subsequently provides a mitogenic and mutagenic environment leading to the development of HCC. Recent in vivo studies have shown that the stress-activated mitogen-activated protein kinase (MAPK) cascade converging on c-Jun NH(2)-terminal kinase (JNK) and p38 plays a central role in these processes, and it has attracted considerable attention as a therapeutic target. However, JNK and p38 have complex functions and a wide range of cellular effects. In addition, crosstalk with each other and the nuclear factor-kappaB pathway further complicate these functions. A full understanding is essential to bring these observations into clinical settings. In this paper, we discuss the latest findings regarding the mechanisms of liver injury and hepatocarcinogenesis focusing on the role of the stress-activated MAPK pathway. PMID- 22666633 TI - Endoscopic-ultrasound-guided fine-needle aspiration and the role of the cytopathologist in solid pancreatic lesion diagnosis. AB - Endoscopic ultrasound (EUS) is the most sensitive imaging modality for solid pancreatic lesions. The specificity, however, is low (about 75%). It can be increased to 100% with an accuracy of 95% by the addition of fine-needle aspiration (FNA). Cytopathology plays an important role. The final diagnosis is based upon the correlation of clinical, EUS, and cytologic features. A close interaction with the cytopathologist is required in improving the diagnostic yield. In this paper, we present an overview of the role of EUS-guided FNA and importance of close interaction with the cytopathologist. Day to day examples of different solid pancreatic lesions have been presented at the end. PMID- 22666634 TI - Modified carbon nanotube paste electrode for voltammetric determination of carbidopa, folic Acid, and tryptophan. AB - A simple and convenient method is described for voltammetric determination of carbidopa (CD), based on its electrochemical oxidation at a modified multiwall carbon nanotube paste electrode. Under optimized conditions, the proposed method exhibited acceptable analytical performances in terms of linearity (over the concentration range from 0.1 to 700.0 MUM), detection limit (65.0 nM), and reproducibility (RSD = 2.5%) for a solution containing CD. Also, square wave voltammetry (SWV) was used for simultaneous determination of CD, folic acid (FA), and tryptophan (TRP) at the modified electrode. To further validate its possible application, the method was used for the quantification of CD, FA, and TRP in urine samples. PMID- 22666635 TI - Automatic and rapid discrimination of cotton genotypes by near infrared spectroscopy and chemometrics. AB - This paper reports the application of near infrared (NIR) spectroscopy and pattern recognition methods to rapid and automatic discrimination of the genotypes (parent, transgenic, and parent-transgenic hybrid) of cotton plants. Diffuse reflectance NIR spectra of representative cotton seeds (n = 120) and leaves (n = 123) were measured in the range of 4000-12000 cm(-1). A practical problem when developing classification models is the degradation and even breakdown of models caused by outliers. Considering the high-dimensional nature and uncertainty of potential spectral outliers, robust principal component analysis (rPCA) was applied to each separate sample group to detect and exclude outliers. The influence of different data preprocessing methods on model prediction performance was also investigated. The results demonstrate that rPCA can effectively detect outliers and maintain the efficiency of discriminant analysis. Moreover, the classification accuracy can be significantly improved by second-order derivative and standard normal variate (SNV). The best partial least squares discriminant analysis (PLSDA) models obtained total classification accuracy of 100% and 97.6% for seeds and leaves, respectively. PMID- 22666636 TI - Neurosarcoidosis and the complexity in its differential diagnoses: a review. AB - While uncommon, neurosarcoidosis has been reported to present similarly to schizophrenia, with auditory hallucinations and delusions. We review the evaluation and work-up of neurosarcoidosis and discuss the differential diagnoses of these psychotic symptoms. PMID- 22666637 TI - Baseline serum prolactin in drug-naive, first-episode schizophrenia and outcome at five years: is it a predictive factor? AB - OBJECTIVE: Serum prolactin is influenced by antipsychotic use but its relationships with psychopathology and general functioning are not clear. This study aimed to assess these relationships. DESIGN: Serum prolactin levels were measured in patients with schizophrenia before being treated with antipsychotics and at various follow-up points. SETTING: The study was conducted in a nongovernmental psychiatric treatment center in Mumbai, India. PARTICIPANTS: The participants included 30 male and 30 female drug-naive patients with schizophrenia and 31 control participants. MEASUREMENTS: The severity of psychopathology at baseline, three weeks, six weeks, and five years following treatment was assessed using a modified Brief Psychiatric Rating Scale. The Global Assessment of Functioning questionnaire was used at baseline and five years follow up. RESULTS: Contrary to our hypotheses, prolactin levels in male but not female patients at baseline were twice those of control volunteers. Correlations between prolactin, Brief Psychiatric Rating Scale, and Global Assessment of Functioning measurements were not significant for any time point up to six weeks, but were only significant at the five-year follow-up appointments, indicating that those patients with higher levels of serum prolactin had a better outcome at five years. CONCLUSION: Baseline serum prolactin levels in drug-naive patients with schizophrenia may be used for long-term prognosis, but are not reliable indicators of psychopathology and prognosis in the short term. Future research is needed to conclude with confidence whether or not prolactin can be used as a biomarker of psychopathological and overall functioning in schizophrenia. PMID- 22666638 TI - Physician grief with patient death. AB - The genuine prevalence and intensity of grief reactions among physicians in response to patient death is unknown. However, a number of authorities and studies indicate that such experiences are fairly commonplace among physicians practicing in the clinical arena. In addition, it appears that the grief response of physicians may be tempered by a number of personal and environmental/contextual factors. A number of authors have proffered various approaches to resolving grief responses in these unique circumstances and many emphasize the importance of doing so in an effort to stave off burnout. PMID- 22666639 TI - Cognitive remediation in severe mental illness. AB - Cognitive enhancement has received substantial recent attention because of multiple recent successes. We review the current research literature on cognitive enhancement, focusing on new developments that separate previous less successful efforts from recent successes. These innovations include increased understanding of the dosing and spacing of sessions, the need for titration of difficulty of individual sessions, and the importance of concurrent interventions. We also review the domains of functioning shown to be improved by cognitive remediation and the possibility that some biomarkers improve as well. We close by noting that current societal factors may impose limitations on the benefits accrued from cognitive remediation and also note that some pharmacological treatments, such as anticholinergic medications, may reduce or eliminate the potential benefits from cognitive remediation. PMID- 22666640 TI - The relationship between various modes of single leg postural control assessment. AB - PURPOSE/BACKGROUND: While various techniques have been developed to assess the postural control system, little is known about the relationship between single leg static and functional balance. The purpose of the current study was to determine the relationship between the performance measures of several single leg postural stability tests. METHODS: Forty six recreationally active college students (17 males, 29 females, 21+/-3 yrs, 173+/-10 cm) performed six single leg tests in a counterbalanced order: 1) Firm Surface-Eyes Open, 2) Firm Surface-Eyes Closed, 3) Multiaxial Surface-Eyes Open, 4) Multiaxial Surface-Eyes Closed, 5) Star Excursion Balance Test (posterior medial reach), 6) Single leg Hop Stabilization Test. Bivariate correlations were conducted between the six outcome variables. RESULTS: Mild to moderate correlations existed between the static tests. No significant correlations existed involving either of the functional tests. CONCLUSIONS: The results indicate that while performance of static balance tasks are mildly to moderately related, they appear to be unrelated to functional reaching or hopping movements, supporting the utilization of a battery of tests to determine overall postural control performance. LEVEL OF EVIDENCE: 3b. PMID- 22666641 TI - The relationship between isotonic plantar flexor endurance, navicular drop, and exercise-related leg pain in a cohort of collegiate cross-country runners. AB - PURPOSE: The purpose of this study was to examine the relationships between isotonic ankle plantar flexor endurance (PFE), foot pronation as measured by navicular drop, and exercise-related leg pain (ERLP). BACKGROUND: Exercise related leg pain is a common occurrence in competitive and recreational runners. The identification of factors contributing to the development of ERLP may help guide methods for the prevention and management of overuse injuries. METHODS: Seventy-seven (44 males, 33 females) competitive runners from five collegiate cross-country (XC) teams consented to participate in the study. Isotonic ankle PFE and foot pronation were measured using the standing heel-rise and navicular drop (ND) tests, respectively. Demographic information, anthropometric measurements, and ERLP history were also recorded. Subjects were then prospectively tracked for occurrence of ERLP during the 2009 intercollegiate cross-country season. Multivariate logistic regression analysis was used to examine the relationships between isotonic ankle joint PFE and ND and the occurrence of ERLP. RESULTS: While no significant differences were identified for isotonic ankle PFE between groups of collegiate XC runners with and without ERLP, runners with a ND >10 mm were almost 7 times (OR=6.6, 95% CI=1.2-38.0) more likely to incur medial ERLP than runners with ND <10 mm. Runners with a history of ERLP in the month previous to the start of the XC season were 12 times (OR=12.3, 95% CI=3.1-48.9) more likely to develop an in-season occurrence of ERLP. CONCLUSION: While PFE did not appear to be a risk factor in the development of ERLP in this group of collegiate XC runners, those with a ND greater than 10 mm may be at greater odds of incurring medial ERLP. LEVEL OF EVIDENCE: 2b. PMID- 22666642 TI - Reliability of three measures of ankle dorsiflexion range of motion. AB - PURPOSE/BACKGROUND: A variety of methods exist to measure ankle dorsiflexion range of motion (ROM). Few studies have examined the reliability of a novice rater. The purpose of this study was to determine the reliability of ankle ROM measurements using three different techniques in a novice rater. METHODS: Twenty healthy subjects (mean+/-SD, age=24+/-3 years, height=173.2+/-8.1 cm, mass=72.6+/ 15.2 kg) participated in this study. Ankle dorsiflexion ROM measures were obtained in a weight-bearing lunge position using a standard goniometer, digital inclinometer, and a tape measure using the distance-to-wall technique. All measures were obtained three times per side, with 10 minutes of rest between the first and second set of measures. Intrarater reliability was determined using an intraclass correlation coefficient (ICC(2,3)) and associated 95% confidence intervals (CI). Standard error of measurement (SEM) and the minimal detectable change (MDC) for each measurement technique were also calculated. RESULTS: The within-session intrarater reliability (ICC(2,3)) estimates for each measure are as follows: tape measure (right 0.98, left 0.99), digital inclinometer (right 0.96; left 0.97), and goniometer (right 0.85; left 0.96). The SEM for the tape measure method ranged from 0.4-0.6 cm and the MDC was between 1.1-1.5 cm. The SEM for the inclinometer was between 1.3-1.4 degrees and the MDC was 3.7-3.8 degrees . The SEM for the goniometer ranged from 1.8-2.8 degrees with an MDC of 5.0-7.7 degrees . CONCLUSIONS: The results indicate that reliable measures of weight bearing ankle dorsiflexion ROM can be obtained from a novice rater. All three techniques had good reliability and low measurement error, with the distance-to wall technique using a tape measure and inclinometer methods resulting in higher reliability coefficients (ICC(2,3)=0.96 to 0.99) and a lower SEM compared to the goniometer (ICC(2,3)=0.85 to 0.96). LEVEL OF EVIDENCE: 2b. PMID- 22666643 TI - An analysis of peak pelvis rotation speed, gluteus maximus and medius strength in high versus low handicap golfers during the golf swing. AB - PURPOSE/HYPOTHESIS: The kinematic sequence of the golf swing is an established principle that occurs in a proximal-to-distal pattern with power generation beginning with rotation of the pelvis. Few studies have correlated the influence of peak pelvis rotation to the skill level of the golfer. Furthermore, minimal research exists on the strength of the gluteal musculature and their ability to generate power during the swing. The purpose of this study was to explore the relationship between peak pelvis rotation, gluteus medius and gluteus maximus strength, and a golfer's handicap. SUBJECTS: 56 healthy subjects. MATERIAL/METHODS: Each subject was assessed using a hand-held dynamometry device per standardized protocol to determine gluteus maximus and medius strength. The K vest was placed on the subject with electromagnetic sensors at the pelvis, upper torso, and gloved lead hand to measure the rotational speed at each segment in degrees/second. After K-vest calibration and 5 practice swings, each subject hit 5 golf balls during which time, the sensors measured pelvic rotation speed. RESULTS: A one-way ANOVA was performed to determine the relationships between peak pelvis rotation, gluteus medius and gluteus maximus strength, and golf handicap. A significant difference was found between the following dependent variables and golf handicap: peak pelvis rotation (p=0.000), gluteus medius strength (p=0.000), and gluteus maximus strength (p=0.000). CONCLUSION: Golfers with a low handicap are more likely to have increased pelvis rotation speed as well as increased gluteus maximus and medius strength when compared to high handicap golfers. CLINICAL RELEVANCE: The relationships between increased peak pelvis rotation and gluteus maximus and medius strength in low handicap golfers may have implications in designing golf training programs. Further research needs to be conducted in order to further explore these relationships. PMID- 22666644 TI - The incidence of low back pain in ncaa division iii female field hockey players. AB - PURPOSE/BACKGROUND: The authors speculated that there may be an increased incidence of low back pain (LBP) in NCAA Division III female field hockey (FH) players. FH players may experience LBP for a variety of reasons including trauma from collisions or falls. Excluding these types of direct trauma, FH players may experience LBP due to excessive stress to spinal structures related to the forward flexed posture that predominates in field hockey. The authors speculated that because of the postural stresses inherent to field hockey there may be an increased incidence of LBP in this population. Therefore, the purpose of this study was to survey NCAA Division III female FH players and an age matched control group to determine if field hockey participation results in an increased incidence of LBP. The anticipated finding of an increased incidence of LBP would provide a rationale for the development of prophylactic interventions for this population. METHODS: SUBJECTS: Female NCAA Division III FH players (n=90) ranging in age from 18-24 years old who participated in the 2008 season were surveyed in regards to the incidence of LBP. A female age-matched control group from Misericordia University (n=98) without a history of field hockey participation was also surveyed. Both groups of subjects completed a voluntary pen and paper survey on the incidence of LBP not related to menstruation. Questions included but were not limited to; whether a significant episode of LBP had been experienced, the mechanism or injury, the duration and nature/location of symptoms. Responses from both groups were anonymous and confidential. RESULTS: There was no difference in the incidence of LBP between the female FH players and the control group (p=0.951). The incidence of LBP was 56% (50/90) in the female FH players and 55% (54/98) in the controls. There was no difference in pain characteristics including pain referral patterns between the 2 groups. However, survey responses revealed a similar mean age of onset of LBP for both groups (16.23 +/- 1.80 years of age for FH players and 16.45 +/- 2.12 years of age for controls). CONCLUSIONS: The data did not support the authors' speculation of a higher incidence of LBP in NCAA Division III female FH players compared to female age-matched controls. This suggests postures associated with field hockey do not appear to significantly increase the incidence of LBP in this population. However, the data revealed that females from both surveyed groups experienced an onset of LBP at a mean age of sixteen. LEVEL OF EVIDENCE: 2b. PMID- 22666645 TI - The reliability and concurrent validity of shoulder mobility measurements using a digital inclinometer and goniometer: a technical report. AB - PURPOSE/AIM: This study investigated the intrarater reliability and concurrent validity of active shoulder mobility measurements using a digital inclinometer and goniometer. MATERIALS/METHODS: Two investigators used a goniometer and digital inclinometer to measure shoulder flexion, abduction, internal and external rotation on 30 asymptomatic participants in a blinded repeated measures design. RESULTS: Excellent intrarater reliability was present with Intraclass Correlation Coefficients (ICC- 3,k) for goniometry >= 0.94 and digital inclinometry >= 0.95. The concurrent validity between goniometry and digital inclinometry was good with ICC (3,k) values of >= 0.85. The 95% limits of agreement suggest that the difference between these two measurement instruments can be expected to range from 2 degrees to 20 degrees . CONCLUSIONS: The results cautiously support the interchangeable use of goniometry and digital inclinometer for measuring shoulder mobility measurements. Although reliable, clinicians should consider the 95% limits of agreement when using these instruments interchangeably as clinically significant differences are likely to be present. LEVEL OF EVIDENCE: 2b. PMID- 22666646 TI - A comparison of topical menthol to ice on pain, evoked tetanic and voluntary force during delayed onset muscle soreness. AB - PURPOSE/BACKGROUND: Pain can adversely affect muscle functioning by inhibiting muscle contractions. Delayed onset muscle soreness was used as a tool to ascertain whether a topical menthol-based analgesic or ice was more effective at reducing pain and permitting greater muscular voluntary and evoked force. METHODS: Sixteen subjects were randomized to receive either a topical gel containing 3.5% menthol or topical application of ice to the non-dominant elbow flexors two days following the performance of an exercise designed to induce muscle soreness. Two days later, DOMS discomfort was treated with a menthol based analgesic or ice. Maximum voluntary contractions and evoked tetanic contractions of the non-dominant elbow flexors were measured at baseline prior to inducing muscle soreness (T1), two days following inducing DOMS after 20 (T2), 25 (T3) and 35 (T4) minutes of either menthol gel or ice therapy. Pain perception using a 10 point visual analog scale was also measured at these four data collection points. Treatment analysis included a 2 way repeated measures ANOVA (2 * 4). RESULTS: Delayed onset muscle soreness decreased (p = 0.04) voluntary force 17.1% at T2 with no treatment effect. Tetanic force was 116.9% higher (p<0.05) with the topical analgesic than ice. Pain perception at T2 was significantly (p=0.02) less with the topical analgesic versus ice. CONCLUSIONS: Compared to ice, the topical menthol-based analgesic decreased perceived discomfort to a greater extent and permitted greater tetanic forces to be produced. LEVEL OF EVIDENCE: Level 2b. PMID- 22666647 TI - Evaluation and treatment of musculoskeletal chest wall pain in a military athlete. AB - BACKGROUND AND PURPOSE: Athletes reporting chest pain are challenging to diagnose and equally challenging to treat. The majority of chest pain is musculoskeletal in origin, yet differentiating these from other more serious conditions should be the initial primary focus. The ability to reproduce the patient's symptoms aids in the differential diagnostic process. The purpose of this case report is to illustrate the use of dry needling (DN) to aid in the diagnosis and treatment of focal chest wall pain. CASE DESCRIPTIONS: A 22 year-old male military athlete with anterior chest pain, refractory to traditional physical therapy, was evaluated and treated with dry needling. OUTCOMES: Favorable results were achieved as demonstrated by clinically meaningful improvements in the Patient Specific Functional Scale, the Global Rating of Change score, and his physical performance which allowed this athlete to return to competition and military training. CONCLUSION: Dry needling in the hands of properly trained providers may aid in diagnosis and treatment of focal chest wall syndromes. LEVEL OF EVIDENCE: Therapy, Level 4. PMID- 22666649 TI - The use of diagnostic musculoskeletal ultrasound to document soft tissue treatment mobilization of a quadriceps femoris muscle tear: a case report. PMID- 22666648 TI - Hamstring injury rehabilitation and prevention of reinjury using lengthened state eccentric training: a new concept. AB - BACK GROUND AND PURPOSE: Hamstring injury is a common occurrence in sport and there has been limited success in reducing this rate of recurrence to date. DESCRIPTION OF TOPIC WITH RELATED EVIDENCE: High speed running requires eccentric strength when the hamstring muscles are in a lengthened state. The lengthened state occurs when the hip is in flexion and the lower leg moves into extension, thus lengthening the two joint hamstring muscle over both articulations upon which they act. There is evidence to suggest that athletes who have sustained a hamstring strain lack strength when the muscle is utilized during performance in a lengthened state. PURPOSE: To examine the risk factors contributing to such a high recurrence rate and propose a unique rehabilitation strategy addressing these factors in order to decrease the rate of reinjury. DISCUSSION/RELATION TO CLINICAL PRACTICE: Failing to increase an athlete's eccentric strength in a lengthened position after a hamstring injury may predispose an athlete to subsequent reinjury. Incorporating lengthened state eccentric training may help reduce the rate of reinjury. LEVEL OF EVIDENCE: Level 5. PMID- 22666650 TI - Management of bleeding and open wounds in athletes. AB - Bleeding or open wounds of the integumentary system occur frequently in athletics. Integumentary wounds vary from minor scrapes, blisters, and small punctures to more serious lacerations and arterial wounds that could threaten the life of the athlete. The Sports physical therapist (PT) must realize that integumentary wounds and subsequent bleeding can occur in many sports, and assessment and care of such trauma is an essential skill. The purpose of this "On the Sidelines" clinical commentary is to review types of integumentary wounds that may occur in sport and their acute management. LEVEL OF EVIDENCE: 5. PMID- 22666651 TI - Professor Dr. Richard Bruynoghe: A 1951 overview of his bacteriophage research spanning three decades. AB - In 1921, Richard Bruynoghe and his student Joseph Maisin published on the first use of bacteriophages in a phage therapy context. At that time, Bruynoghe (a medical doctor) was affiliated as a professor at the KU Leuven (Belgium) for just over a decade, within the Bacteriological Institute which he founded and led. After a distinguished career (he was acting mayor of the city of Leuven-Belgium during the second World War), he received a special medical award in 1951 just before his retirement in 1952. In this perspective, he was asked to provide an overview of his research for a lay-audience within the local University magazine: Onze Alma Mater (Our alma mater). We, as current affiliates of the KU Leuven are honored to present some of his legacy, which to date has been largely overlooked in historical accounts. PMID- 22666652 TI - Recombineering: A powerful tool for modification of bacteriophage genomes. AB - Recombineering, a recently developed technique for efficient genetic manipulation of bacteria, is facilitated by phage-derived recombination proteins and has the advantage of using DNA substrates with short regions of homology. This system was first developed in E. coli but has since been adapted for use in other bacteria. It is now widely used in a number of different systems for a variety of purposes, and the construction of chromosomal gene knockouts, deletions, insertions, point mutations, as well as in vivo cloning, mutagenesis of bacterial artificial chromosomes and phasmids, and the construction of genomic libraries has been reported. However, these methods also can be effectively applied to the genetic modification of bacteriophage genomes, in both their prophage and lytically growing states. The ever-growing collection of fully sequenced bacteriophages raises more questions than they answer, including the unknown functions of vast numbers of genes with no known homologs and of unknown function. Recombineering of phage genomes is central to addressing these questions, enabling the simple construction of mutants, determination of gene essentiality, and elucidation of gene function. In turn, advances in our understanding of phage genomics should present similar recombineering tools for dissecting a multitude of other genetically naive bacterial systems. PMID- 22666653 TI - Surface-immobilization of chromatographically purified bacteriophages for the optimized capture of bacteria. AB - Bacteriophages offer interesting alternatives to antibodies for the specific capture and detection of pathogenic bacteria onto biosensing surfaces. Procedures for the optimal chemical immobilization of lytic bacteriophages onto surfaces are presented. More specifically, the removal of lysate contaminants from bacteriophage suspensions by size exclusion chromatography significantly increases the resultant planar surface density of immobilized bacteriophages. E. coli T4 and Salmonella enterica serovar Typhimurium P22 phage systems seem to undergo highly heterogeneous adsorption to the surface, possibly explaining the observed phage clustering at higher surface densities. The T4 phage and its E. coli host were initially employed as a model system where we discovered an optimal planar surface density of phages for best bacterial capture: 18.9 +/- 0.8 phages/MUm(2) capturing 18.0 +/- 0.3 bacteria/100 MUm(2). Phage surface clustering ultimately limits the T4 phage-immobilized surface's ability to specifically capture its host bacteria. Nevertheless, this is to our knowledge the largest surface capture density of E. coli reported using intact T4 bacteriophages. Two additional purified bacteriophage systems (P22 and Campylobacter jejuni phage NCTC 12673) were then similarly studied for their ability to capture their corresponding host bacteria (Salmonella enterica serovar Typhimurium and Campylobacter jejuni respectively) on a surface. PMID- 22666654 TI - Islands of non-essential genes, including a DNA translocation operon, in the genome of bacteriophage 0305phi8-36. AB - We investigate genes of lytic, Bacillus thuringiensis bacteriophage 0305phi8-36 that are non-essential for laboratory propagation, but might have a function in the wild. We isolate deletion mutants to identify these genes. The non permutation of the genome (218.948 Kb, with a 6.479 Kb terminal repeat and 247 identified orfs) simplifies isolation of deletion mutants. We find two islands of non-essential genes. The first island (3.01% of the genomic DNA) has an informatically identified DNA translocation operon. Deletion causes no detectable growth defect during propagation in a dilute agarose overlay. Identification of the DNA translocation operon begins with a DNA relaxase and continues with a translocase and membrane-binding anchor proteins. The relaxase is in a family, first identified here, with homologs in other bacteriophages. The second deleted island (3.71% of the genome) has genes for two metallo-protein chaperonins and two tRNAs. Deletion causes a significant growth defect. In addition, (1) we find by "in situ" (in-plaque) single-particle fluorescence microscopy that adsorption to the host occurs at the tip of the 486 nm long tail, (2) we develop a procedure of 0305phi8-36 purification that does not cause tail contraction, and (3) we then find by electron microscopy that 0305phi8-36 undergoes tail tip-tail tip dimerization that potentially blocks adsorption to host cells, presumably with effectiveness that increases as the bacteriophage particle concentration increases. These observations provide an explanation of the previous observation that 0305phi8-36 does not lyse liquid cultures, even though 0305phi8-36 is genomically lytic. PMID- 22666655 TI - The C-terminal cysteine annulus participates in auto-chaperone function for Salmonella phage P22 tailspike folding and assembly. AB - Elongated trimeric adhesins are a distinct class of proteins employed by phages and viruses to recognize and bind to their host cells, and by bacteria to bind to their target cells and tissues. The tailspikes of E. coli phage K1F and Bacillus phage O29 exhibit auto-chaperone activity in their trimeric C-terminal domains. The P22 tailspike is structurally homologous to those adhesins. Though there are no disulfide bonds or reactive cysteines in the native P22 tailspikes, a set of C terminal cysteines are very reactive in partially folded intermediates, implying an unusual local conformation in the domain. This is likely to be involved in the auto-chaperone function. We examined the unusual reactivity of C-terminal tailspike cysteines during folding and assembly as a potential reporter of auto chaperone function. Reaction with IAA blocked productive refolding in vitro, but not off-pathway aggregation. Two-dimensional PAGE revealed that the predominant intermediate exhibiting reactive cysteine side chains was a partially folded monomer. Treatment with reducing reagent promoted native trimer formation from these species, consistent with transient disulfide bonds in the auto-chaperone domain. Limited enzymatic digestion and mass spectrometry of folding and assembly intermediates indicated that the C-terminal domain was compact in the protrimer species. These results indicate that the C-terminal domain of the P22 tailspike folds itself and associates prior to formation of the protrimer intermediate, and not after, as previously proposed. The C-terminal cysteines and triple beta-helix domains apparently provide the staging for the correct auto-chaperone domain formation, needed for alignment of P22 tailspike native trimer. PMID- 22666656 TI - Bacterial 'immunity' against bacteriophages. AB - Vertebrate animals possess multiple anti-pathogen defenses. Individual mechanisms usually are differentiated into those that are immunologically adaptive vs. more "primitive" anti-pathogen phenomena described as innate responses. Here I frame defenses used by bacteria against bacteriophages as analogous to these animal immune functions. Included are numerous anti-phage defenses in addition to the adaptive immunity associated with CRISPR/cas systems. As these other anti pathogen mechanisms are non-adaptive they can be described as making up an innate bacterial immunity. This exercise was undertaken in light of the recent excitement over the discovery that CRISPR/cas systems can serve, as noted, as a form of bacterial adaptive immunity. The broader goal, however, is to gain novel insight into bacterial defenses against phages by fitting these mechanisms into considerations of how multicellular organisms also defend themselves against pathogens. This commentary can be viewed in addition as a bid toward integrating these numerous bacterial anti-phage defenses into a more unified immunology. PMID- 22666657 TI - Who went into phage research? AB - A total of 30,000 phage papers, books, or book chapters, published between 1965 and 2010, were analyzed for the ethnic origins of 14,429 first authors. Their names represent 40 linguistic domains or geographic areas and at least 70 languages. British and German names predominate. Results broadly concur with statistics on the frequency of publications by country and show the growing role of Third-World countries in phage research. Irish and Jewish scientists are prominent. Historical and societal factors appear to be very important elements in the advancement of science. PMID- 22666658 TI - A Density Functional Theory Evaluation of Hydrophobic Solvation: Ne, Ar and Kr in a 50-Water Cluster. Implications for the Hydrophobic Effect. AB - The physical explanation for the hydrophobic effect has been the subject of disagreement. Physical organic chemists tend to use a explanation related to pressure, while many biochemists prefer an explanation that involves decreased entropy of the aqueous solvent. We present DFT calculations at the B3LYP/6 31G(d,p) and X3LYP/6-31G(d,p) levels on the solvation of three noble gases (Ne, Ar, and Kr) in clusters of 50 waters. Vibrational analyses show no substantial decreases in the vibrational entropies of the waters in any of the three clusters. The observed positive free energies of transfer from the gas phase or from nonpolar solvents to water appear to be due to the work needed to make a suitable hole in the aqueous solvent. We distinguish between hydrophobic solvations (explicitly studied here) and the hydrophobic effect that occurs when a solute (or transition state) can decrease its volume through conformational change (which is not possible for the noble gases). PMID- 22666659 TI - Investigational approaches for mesothelioma. AB - Malignant pleural mesothelioma (MPM) is a rare, aggressive tumor with a poor prognosis. In view of the poor survival benefit from first-line chemotherapy and the lack of subsequent effective treatment options, there is a strong need for the development of more effective treatment approaches for patients with MPM. This review will provide a comprehensive state of the art of new investigational approaches for mesothelioma. In an introductory section, the etiology, epidemiology, natural history, and standard of care treatment for MPM will be discussed. This review provide an update of the major clinical trials that impact mesothelioma treatment, discuss the impact of novel therapeutics, and provide perspective on where the clinical research in mesothelioma is moving. The evidence was collected by a systematic analysis of the literature (2000-2011) using the databases Medline (National Library of Medicine, USA), Embase (Elsevier, Netherlands), Cochrane Library (Great Britain), National Guideline Clearinghouse (USA), HTA Database (International Network of Agencies for Health Technology Assessment - INAHTA), NIH database (USA), International Pleural Mesothelioma Program - WHOLIS (WHO Database), with the following keywords and filters: mesothelioma, guidelines, treatment, surgery, chemotherapy, radiotherapy, review, investigational, drugs. Currently different targeted therapies and biologicals are under investigation for MPM. It is important that the molecular biologic research should first focus on mesothelioma-specific pathways and biomarkers in order to have more effective treatment options for this disease. The use of array technology will be certainly an implicit gain in the identification of new potential prognostic or biomarkers or important pathways in the MPM pathogenesis. Probably a central mesothelioma virtual tissue bank may contribute to the ultimate goal to identify druggable targets and to develop personalized treatment for the MPM patients. PMID- 22666660 TI - Genomics of acute myeloid leukemia: the next generation. AB - Acute myeloid leukemia (AML) is, as other types of cancer, a genetic disorder of somatic cells. The detection of somatic molecular abnormalities that may cause and maintain AML is crucial for patient stratification. The development of mutation-specific therapeutic interventions will hopefully increase cure rates and improve patients' quality of life. This review illustrates how next generation sequencing technologies are changing the study of cancer genomics of adult AML patients. PMID- 22666661 TI - Survival outcomes of patients treated with hypofractionated stereotactic body radiation therapy for parotid gland tumors: a retrospective analysis. AB - BACKGROUND: to review a single-institution experience with the management of parotid malignancies treated by fractionated stereotactic body radiosurgery (SBRT). FINDINGS: Between 2003 and 2011, 13 patients diagnosed with parotid malignancies were treated with adjuvant or definitive SBRT to a median dose of 33 Gy (range 25-40 Gy). There were 11 male and two female patients with a median age of 80. Ten patients declined conventional radiation treatment and three patients had received prior unrelated radiation therapy to neighboring structures with unavailable radiation records. Six patients were treated with definitive intent while seven patients were treated adjuvantly for adverse surgical or pathologic features. Five patients had clinical or pathologic evidence of lymph node disease. CONCLUSION: at a median follow-up of 14 months only one patient failed locally, and four failed distantly. The actuarial 2-year overall survival, progression-free survival, and local-regional control rates were 46, 84, and 47%, respectively. Statistical analysis revealed surgery as a positive predictor of overall survival while presence of gross disease was a negatively correlated factor (p < 0.05). PMID- 22666663 TI - A newborn arrives with the gene for infinite possibilities. PMID- 22666662 TI - A Phase I Study of Dasatinib with Concurrent Chemoradiation for Stage III Non Small Cell Lung Cancer. AB - OBJECTIVES: Src family kinases (SFKs) are expressed in non-small cell lung cancer (NSCLC) and may be involved in tumor growth and metastases. Inhibition of SFK may also enhance radiation. The purpose of this study was to evaluate if a maximum dose of 100 mg of dasatinib could be safely administered with concurrent chemoradiation and then continued as maintenance for patients with newly diagnosed stage III NSCLC. METHODS: Patients with stage III locally advanced NSCLC received paclitaxel, 50 mg/m(2)/week, with carboplatin area under the curve (AUC) = 2, weekly for 7 weeks, and concurrent radiotherapy, 64.8 Gy. Three dose levels of dasatinib 50, 70, and 100 mg/day were planned. RESULTS: 11 patients with locally advanced NSCLC were entered. At the 70 mg dose level 1 patient had grade 5 pneumonitis not responsive to therapy, and one patient had reversible grade 3 pneumonitis and grade 3 pericardial effusion. Due to these toxicities the Brown University Oncology Group Data Safety Monitoring Board terminated the study. CONCLUSION: Dasatinib could not be safely combined with concurrent chemoradiation for stage 3 lung cancer due to pneumonitis. PMID- 22666664 TI - Concurrent exposure to microbial products and food antigens triggers initiation of food allergy. AB - It is estimated that as much as 6-8% population suffers from food allergy or food antigen-related disorders. The prevalence keeps rising. So far we do not have identified remedy to treat food allergy. Avoidance of the offending food is the only effective method currently. Skewed T helper 2 polarization is one of the major feature in the pathogenesis of food allergy. However, the causative mechanism in the initiation of food allergy remains to be further understood. Research in food allergy has got giant advance in recent years. Several animal models have been established and used in food allergy study. One of the common features of these food allergy animal models is that most of them require using microbial products as adjuvant to sensitize animals. This review documents the recent advance in the mechanistic study on concurrent use of microbial products and food antigens to study food allergy. PMID- 22666665 TI - Regulatory effect of heat shock protein 70 in stress-induced rat intestinal epithelial barrier dysfunction. AB - BACKGROUND: Psychological stress is one of the factors associated with many human diseases; the mechanisms need to be further understood. METHODS: Rats were subjected to chronic water avoid stress. Intestinal epithelial heat shock protein (HSP) 70 was evaluated. The intestinal epithelial permeability was examined with Ussing chamber technique. RESULTS: HSP70 was detected in normal intestinal epithelial cells. Psychological stress decreased HSP70 in the intestinal epithelial cells that correlated with the stress-induced intestinal epithelial hyperpermeability. Pretreatment with HSP70 abrogated stress-induced intestinal barrier dysfunction. CONCLUSIONS: Chronic stress inhibits HSP70 activity in rat intestinal epithelial layer that is associated with intestinal epithelial barrier dysfunction, which can be prevented by pretreatment with HSP70 protein. (Yang PC, Tu YH, Perdue MH, Oluwole C, Struiksma S. Regulatory effect of heat shock protein 70 in stress-induced rat intestinal epithelial barrier dysfunction. PMID- 22666666 TI - Mast cells modulate transport of CD23/IgE/antigen complex across human intestinal epithelial barrier. AB - BACKGROUND: Food allergy and chronic intestinal inflammation are common in western countries. The complex of antigen/IgE is taken up into the body from the gut lumen with the aid of epithelial cell-derived CD23 (low affinity IgE receptor II) that plays an important role in the pathogenesis of intestinal allergy. This study aimed to elucidate the role of mast cell on modulation of antigen/IgE complex transport across intestinal epithelial barrier. METHODS: Human intestinal epithelial cell line HT29 cell monolayer was used as a study platform. Transepithelial electric resistance (TER) and permeability to ovalbumin (OVA) were used as the markers of intestinal epithelial barrier function that were recorded in response to the stimulation of mast cell-derived chemical mediators. RESULTS: Conditioned media from naive mast cell line HMC-1 cells or monocyte cell line THP-1 cells significantly upregulated the expression of CD23 and increased the antigen transport across the epithelium. Treatment with stem cell factor (SCF), nerve growth factor (NGF), retinoic acid (RA) or dimethyl sulphoxide (DMSO) enhanced CD23 expression in HT29 cells. Conditioned media from SCF, NGF or RA-treated HMC-1 cells, and SCF, NGF, DMSO or RA-treated THP-1 cells enhanced immune complex transport via enhancing the expression of the CD23 in HT29 cells and the release of inflammatory mediator TNF-alpha. Nuclear factor kappa B inhibitor, tryptase and TNF-alpha inhibited the increase in CD23 in HT29 cells and prevents the enhancement of epithelial barrier permeability. CONCLUSIONS: Mast cells play an important role in modulating the intestinal CD23 expression and the transport of antigen/IgE/CD23 complex across epithelial barrier. (Tu YH, Oluwole C, Struiksma S, Perdue MH, Yang PC. Mast cells modulate transport of CD23/IgE/antigen complex across human intestinal epithelial barrier. PMID- 22666667 TI - Laparoscopic distal pancreatectomy with preservation of the spleen and splenic vessels for pancreatic adenocarcinoma. AB - BACKGROUND: A laparoscopic surgery can be beneficial in a spleen-preserving distal pancreatectomy. AIMS: This report shows a 60-year-old woman who presented with persistent upper abdominal and bilateral lumbodorsal distending pain for one year. A computed tomography scan demonstrated a 4cm*5cm*5cm solid space-occupying mass in the distal pancreas. The patient was referred to minimally invasive surgery service for resection of the pancreatic lesion. METHODS: A laparoscopic spleen-preserving distal pancreatectomy was performed. RESULTS: The mass was completely excised, the pathological examination revealed grade II pancreatic adenocarcinoma. The postoperative advantages of this approach were the early return of bowel function, minimal complications, and early resumption of normal activities. CONCLUSIONS: This case illustrates that minimally invasive surgery in the performance of a spleen-and-splenic-vessel preserving distal pancreatectomy is a feasible procedure without compromising the splenic function. (Wang WJ, Li JG, Li ZT, Fang Q, Zheng YG. Laparoscopic distal pancreatectomy with preservation of the spleen and splenic vessels for pancreatic adenocarcinoma. PMID- 22666669 TI - Type 1 diabetes risk and autoantibody positivity in Sardinian migrants in the province of Pavia. AB - BACKGROUND: Type 1 diabetes is an autoimmune disease. Genetics as well as environmental factors seem to play a role in the pathogenesis of type 1 diabetes. AIMS: We sought to investigate the possible relationship between migration from Sardinia to a low incidence area of type 1 diabetes (Lombardy) and the prevalence of autoantibody positivity. METHODS: We enrolled 554 Sardinian immigrants and 226 of their offspring. All subjects underwent a complete anamnestic evaluation. Fasting blood glucose, HbA1c, GADA and IA-2 were measured in all study participants. Additionally, the presence of risk haplotypes (HLA-DR3 -DR4 and DQB1/0302) was determined. After a seven-year follow-up, high genetic risk and/or autoantibody positivity subjects were re-evaluated. RESULTS: Among Sardinian immigrants, the prevalence of type 1 diabetes was 0.9%, while in the offspring group, the prevalence was 0.4%. After removing type 1 diabetic patients, the GADA prevalence was 2.4% in the immigrant group and 3.8% among their offspring. Among Sardinian immigrants, the IA-2 prevalence was 0.7%, while all offspring were IA-2 negative. After a seven-year follow-up, 85.7% of GADA-positive migrants had persistent GADA positivity. Two GADA-negative offspring subjects turned positive. None of the study participants developed diabetes during the follow-up. CONCLUSIONS: The present study showed a higher prevalence of GADA positivity within Sardinian immigrants at high genetic risk; GADA positivity may represent the first detectable phase of type 1 diabetes. After a seven-year follow-up, none of the high genetic/antibody risk group subjects developed type 1 diabetes. However, it seems reasonable to strictly control high-risk individuals in order to diagnose subclinical diabetes. PMID- 22666670 TI - Recurrence of urinary retention secondary to retroverted gravid uterus. AB - BACKGROUND: Although urinary retention caused by the retroverted gravid uterus is uncommon, acute urinary retention is an emergency condition. CASES: We present here two cases of acute urinary retention at 12 weeks' gestation secondary to retroverted gravid uterus. Although some preventive measures were suggested to the patients, recurrences of urinary retention occurred during the following 2-3 weeks and in their next pregnancies. CONCLUSION: In cases that urinary retention due to retroverted gravid uterus once occurred, we have to pay attention to the recurrence of urinary retention during the next pregnancies. PMID- 22666671 TI - Removal of ovarian hormones affects the ageing process of acetate metabolism. AB - BACKGROUND: Despite a close association between gastrointestinal motility and sex hormones, it has been unknown whether ovarian hormones affect absorption and metabolism of nutrients. The aim of this study is, therefore, to evaluate metabolism of acetate in rats with age and the influence of ovariectomy on its change. METHODS: Fourteen female rats of the F344 strain were used, and 13C acetate breath test was performed at 2, 7 and 13 months of age. Seven rats were ovariectomized at three weeks of age (ovariectomy group) and the remaining seven rats were studied as control group. After 24-hr fasting, rats are orally administrated 1ml of water containing sodium (13)C-acetate (100mg/kg) and housed in an animal chamber. The expired air in the chamber is collected in a breath sampling bag using a aspiration pump. The (13)CO(2) concentration is measured using an infrared spectrometer for 120 min and expressed as delta per mil. RESULTS: The breath (13)CO(2) excretion increased with time and peaked 30 min in control rats. In ovariectomized rats, thee peak time of (13)CO(2) excretion was prolonged to 40 min at 7 and 13 months of age. Cmax was significantly higher at 2 months of age but lower at 4 months of age in ovariectomized rats than in control rats. Those of two groups became equal at 7 months of age. CONCLUSIONS: From the viewpoint of acetate metabolism, removal of ovarian hormones might make rats to be precocious ones and accelerate ageing. PMID- 22666668 TI - What is regressive autism and why does it occur? Is it the consequence of multi systemic dysfunction affecting the elimination of heavy metals and the ability to regulate neural temperature? AB - There is a compelling argument that the occurrence of regressive autism is attributable to genetic and chromosomal abnormalities, arising from the overuse of vaccines, which subsequently affects the stability and function of the autonomic nervous system and physiological systems. That sense perception is linked to the autonomic nervous system and the function of the physiological systems enables us to examine the significance of autistic symptoms from a systemic perspective. Failure of the excretory system influences elimination of heavy metals and facilitates their accumulation and subsequent manifestation as neurotoxins: the long-term consequences of which would lead to neurodegeneration, cognitive and developmental problems. It may also influence regulation of neural hyperthermia. This article explores the issues and concludes that sensory dysfunction and systemic failure, manifested as autism, is the inevitable consequence arising from subtle DNA alteration and consequently from the overuse of vaccines. PMID- 22666672 TI - Esophageal stent migration can lead to intestinal obstruction. AB - BACKGROUND: Self-expanding metallic stents are the devices of choice in the treatment of malign or benign strictures of the esophagus. Stent migration is a well-known complication of this procedure. AIMS: We report a case of intestinal obstruction caused by esophageal stent migration, in which surgical intervention was used. METHODS: A 65-year-old woman, who had a medical history of gastric cancer operations and esophageal stent applications, was admitted to our emergency department with a 48-hour history of abdominal pain, nausea and vomiting. An emergency laparotomy was performed and the migrated stent causing intestinal obstruction was removed. RESULTS: The patient recovered without incident and was discharged on postoperative day 3. CONCLUSION: This case illustrates that esophageal stent migration has to be considered as a potential life-threatening complication. PMID- 22666673 TI - Visual characteristics of the papilla to estimate cannulation of the common bile duct - a pilot study. AB - OBJECTIVES: Performance of endoscopic retrograde cholangiography (ERC) depends mainly on the skills of the examiner, but also on anatomical variants. The aim of the study was to investigate patient- and papilla-related factors for the successful selective cannulation of the common bile duct (CBD). PATIENTS AND METHODS: 50 patients with a papilla with no prior sphincterotomy needing an ERC were enrolled. From a standardized description given by the endoscopist, criteria to characterize the papilla were analyzed. RESULTS: Success was achieved in 92%. Cannulation time was 460 +/- 561 seconds on average. 70% of the papillae were mastered in 300 seconds or less. Concordance between endoscopists concerning descriptive variables was between 86% and 100%. The judgment of the endoscopist concerning expected difficulty was not significantly related to success, demonstrating the necessity of predictive parameters. Typical position of the duodenoscope and performance of precut were significantly related to success. The joint presence of a visible orifice and a typical position of the duodenoscope had a positive predictive value (PPV) of 96%. CONCLUSIONS: Endoscopists can rely on the joint presence of a visible orifice of the papilla and a typical position of the duodenoscope in X-ray to predict the success of ERC. PMID- 22666674 TI - Wilson's disease masquerading as nonalcoholic steatohepatitis. AB - BACKGROUND: Wilson's disease is one of the most common hereditary causes of unclear hepatopathy. PATIENT #ENTITYSTARTX00026; METHOD: A 34-year old male patient with a history of hyperlipidemia was admitted with symptoms of abdominal pain and slight hematuria. Abnormal liver function tests, ultrasound reports and liver biopsy were suggestive of nonalcoholic steatohepatitis (NASH). The patient received preliminary treatment for NASH. However, on subsequent follow-up, NASH remained unresolved and liver histology showed fibrosis progression from fibrosis stage 1 to stage 3. RESULTS: Biochemical tests revealed that the levels of serum ceruloplasmin were decreased (7mg/dl) while the urinary excretion of copper was found to be increased (174.2 MUg/day). Wilson's disease was confirmed by diagnostic mutation analysis involving Direct Sequencing. Heterogeneity in the patient's ATP7B gene confirmed Wilson's disease. Administration of D penicillamine resulted in a decrease in fat deposition in the liver and no further progression in fibrosis after 10 months. CONCLUSION: Adult patient presenting NASH as first symptoms need to be examined for Wilson's disease and other metabolic conditions affecting the liver, prior to initiation of treatment. PMID- 22666675 TI - Primary spinal extradural hydatid cyst associated with acute bleeding. AB - AIMS: The purpose of this article is to report a case of unilocular primary spinal extradural hydatid cyst which manifested as acute bleeding. METHODS: The clinical presentation, diagnosis, and surgical treatment of this rare case are discussed and published cases of primary extradural hydatid cysts are reviewed. RESULTS: Complete recovery was achieved. Repeated clinical, radiological, and serological examinations did not show any evidence of local recurrence or systemic hydatidosis during the follow-up period of 50 months. CONCLUSIONS: Primary spinal extradural hydatid cyst may present as acute bleeding. PMID- 22666676 TI - Anesthetic management for an infant undergoing endoscopic resection of a large subglottic papiloma. AB - BACKGROUND: An infant with a large subglottic papilloma that caused severe respiratory distress needed anesthesia during resection of the papilloma. AIMS: We planned an approach to the airway management this infant that we thought would be successful. METHODS: We used three main tactics in managing the airway - inhaled sevoflurane, intravenous fentanyl and the patient's resumed spontaneous breathing. We also allowed the otolaryngologist to quickly resect some of the papilloma before intubation. RESULTS: Our patient's airway was managed successfully, and the papilloma was removed. CONCLUSIONS: Management of the airway in a small child with obstruction can be aided by inducing anesthesia with sevoflurane, deepening anesthesia with intravenous fentanyl, and allowing the patient to resume spontaneous breathing. PMID- 22666677 TI - A theoretical framework of the good health status of Jamaicans: using econometric analysis to model good health status over the life course. AB - BACKGROUND: In recent times, the World Health Organization has increasing drawn attention to the pivotal role of social conditions in determining health status. The non-biological factors produced inequalities in health and need to be considered in health development. In spite of this, extensive review of health Caribbean revealed that no study has examined health status over the life course of Jamaicans. With the value of research in public health, this study is timely and will add value to understand the elderly, middle age and young adults in Jamaica. OBJECTIVE: The aim of this study is to develop models that can be used to examine (or evaluate) health of Jamaicans, elderly, middle age and young adults. METHOD: The current study used data from a cross-sectional survey which was conducted between July and October 2002. Stratified random probability sampling technique was used to collect the data from 25,018 respondents across the island. The non-response rate for the survey was 29.7% with 20.5% who did not respond to particular questions, 9.0% did not participated in the survey and another 0.2% was rejected due to data cleaning. Logistic regression analyses were used to model health status of Jamaicans, young adults, middle age adults and elderly. The predictive power of the model was tested using Omnibus Test of Model and Hosmer and Lemeshow (24) was used to examine goodness of fit of the model. The correlation matrix was examined in order to ascertain whether autocorrelation (or multi-collinearity) existed between variables. RESULTS: Using logistic regression analysis, eleven variables emerged as statistically significant predictors of current good health Status of Jamaicans (p<0.05). The factors are retirement income (95%CI=0.487-0.958), logged medical expenditure (95% Confidence Interval, CI =0.907-0.993), marital status (Separated or widowed or divorced: 95%CI=0.309-0.464; married: 95%CI=0.495-0.667; Never married), health insurance (95%CI=0.029-0.046), area of residence (other towns:, 95%CI=1.052-1.455; rural area:), education (secondary: 95%CI=1.167-1.576; tertiary: 95%CI=1.466-2.820; primary or below: OR=1.00), social support (95%CI=0.745-0.964), gender (95%CI=1.281-1.706), psychological affective conditions (negative affective: 95%CI=0.939-0.980; positive affective: 95%CI:1.047-1.107), number of males in household (95%CI:1.066-1.235), number of children in household (95%CI=1.117 1.266) and previous health status. CONCLUSION: The study concludes that good health status across the three age cohorts can be modelled using data for Jamaicans. Health status is determined by a number of non-biological factors, and that poor health status is difficult to model as a low proportion of the data was correctly classified. Public health requires research with which to make more informed decisions, which means that this study offers an understanding of Jamaicans as well as young adults; middle aged adults and elderly. PMID- 22666678 TI - Oseltamivir resistance in swine influenza: a brief discussion. AB - Swine flu, an atypical H1N1 influenza virus infection, is a new emerging infectious disease starting from Mexico in 2009, and is presently pandemic around the world. For treatment of this infection, oseltamivir is recommended as drug of choice. Generally, a big problem for using oseltamivir in treatment of classical H1NI influenza virus infection is drug resistance. In this brief paper, the author discusses on the situation of oseltamivir resistance in swine influenza. Briefly, the oseltamivir resistance of swine flu is expected to be possible due to many underlying factors. It is needed to perform surveillance on oseltamivir resistance in swine flu. Planning for management of case of emerging oseltamivir drug resistance is needed. PMID- 22666679 TI - Impact of poverty, not seeking medical care, unemployment, inflation, self reported illness, and health insurance on mortality in Jamaica. AB - BACKGROUND: An extensive review of the literature revealed that no study exists that has examined poverty, not seeking medical care, inflation, self-reported illness, and mortality in Jamaica. The current study will bridge the gap by providing an investigation of poverty; not seeking medical care; illness; health insurance coverage; inflation and mortality in Jamaica. MATERIALS AND METHOD: Using two decades (1988-2007), the current study used three sets of secondary data published by the (1) Planning Institute of Jamaica and the Statistical Institute of Jamaica (Jamaica Survey of Living Conditions) (2) the Statistical Institute of Jamaica (Demographic Statistics) and (3) the Bank of Jamaica (Economic Report). Scatter diagrams were used to examine correlations between the particular dependent and independent variables. For the current study, a number of hypotheses were tested to provide explanation morality in Jamaica. RESULTS: The average percent of Jamaicans not seeking medical care over the last 2 decades was 41.9%; and the figure has been steadily declining over the last 5 years. In 1990, the most Jamaicans who did not seek medical care were 61.4% and this fell to 52.3% in 1991; 49.1% in 1992 and 48.2% the proceeding year. Based on the percentages, in the early 1990s (1990-1994), the percent of Jamaicans not seeking medical care was close to 50% and in the latter part of the decade, the figure was in the region of 30% and the low as 31.6% in 1999. In 2006, the percent of Jamaicans not seeking medical care despite being ill was 30% and this increased by 4% the following year. Concomitantly, poverty fell by 3.1 times over the 2 decades to 9.9% in 2007, while inflation increased by 1.9 times, self-reported illness was 15.5% in 2007 with mortality averaging 15,776 year of the 2 decades. There is a significant statistical correlation between not seeking medical-care and prevalence of poverty (r = 0.759, p< 0.05). There is a statistical correlation between not seeking medical care and unemployment; but the association is a non-linear one. The relationship between mortality and unemployment was an unsure one, with there being no clear linear or non-linear correlation. The findings revealed that there is a strong direct association between not seeking medical care and inflation rate (r = 0.752). A strong negative statistical correlation was found between mortality and prevalence of poverty (r=0.717). There is a non-linear statistical association between not seeking medical care and illness/injury. CONCLUSIONS: Not seeking medical care is not a good indicator of premature mortality; but that this percentage must be excess of 55%. While this study cannot confirm a clear rate of premature mortality, there are some indications that this occurs beyond a certain level of not seeking care for illness. PMID- 22666680 TI - Whole blood viscosity determination in diabetes management: perspective in practice. AB - BACKGROUND: Antiplatelet and antioxidant nutritional therapies (ANT) are commonly used in diabetes management. Guidelines recommend identifying deficiencies of antioxidant vitamins and condition of no contraindication for nutritional and antiplatelet respectively. AIM: To determine whether the guidelines recommendations for diabetes patients to be assessed for (1) antioxidant vitamins' deficiencies and/or (2) whole blood viscosity (WBV) as indication of no antiplatelet contraindication. MATERIALS AND METHOD: Laboratory records were audited. 10,342 de-identified glycaemic index (HbA1(c)) requests received in 2008 were sorted into three groups based on level of control. (1) Poor (n = 1962, HbA1(c) >= 8.1); (2) Good (n = 5616, HbA1(c) = 6.0 - 8.0) and (3) Excellent (n = 2764, HbA1(c) <= 5.9). All 57 cases with haematocrit and total protein results in the poor (n=30) and excellent (n=27) groups were selected for calculation and comparison of WBV levels. RESULTS: None of the two guidelines' recommendations are being followed as no case was requested for any antioxidant vitamin or WBV. Assessments of the latter show that WBV is statistically significantly lower (p < 0.05) in the group with excellent glycaemic control compared to the group with poor glycaemic control. CONCLUSION: Aspirin is one of the therapies in diabetes management. Its effect is modulated by WBV. ANT is alternative to aspirin and influences WBV. For patients that have full blood count and plasma protein results, WBV can be extrapolated at no extra cost to the health system. There is a need to raise awareness for the recommended guidelines for laboratory monitoring to be followed. PMID- 22666681 TI - Emphysematous cystitis of the diabetic patient. AB - BACKGROUND: Emphysematous cystitis is defined by the presence of gas in the urinary bladder wall. It complicates urinary tract infections especially in diabetic patients. AIMS: We present a case of emphysematous cystitis in a diabetic patient with a poor glycemia control and we discuss diagnostics and treatment items of this uncommon and serious infection. METHODS AND RESULTS: A 45 year-old man was admitted to the emergency department with confusion and abdominal pain. The clinical examination found a septic shock the Ultra sonography (US) showed a cholecystitis the patient was operated without amelioration. A post operative pelvic computed tomography (CT) demonstrated intramural gas in the urinary bladder, which suggested a diagnosis of emphysematous cystitis. The treatment was based on an antibiotics associated with a bladder drainage. The evolution was in favor. CONCLUSION: Every diabetic patient with a urinary tract infection who seems to be severely ill should have an abdominal X-ray as a minimal screening tool to detect emphysematous complications. PMID- 22666682 TI - Dyshidrotic eczema: relevance to the immune response in situ. AB - CONTEXT: Pompholyx (called dyshidrosis by some) is one of the most common conditions and its immune response is presently poorly understood. CASE REPORT: We describe a 58 year old African American female with a clinical history of rheumatoid arthritis and type II diabetes who presented a chronic five-year, itchy vesicular/blistering rash involving her hands and feet. A lesional skin biopsy was taken for hematoxylin and eosin (H & E) analysis. In addition, a multicolor direct immunofluorescence (MDIF) and immunohistochemistry (IHC) studies were performed. The major findings to be reported were: the H & E examination revealed spongiotic dermatitis and pompholix. IHC and MDIF studies demonstrated focally deposits of positive CD45, CD3, CD8, anti myeloperoxidase (MPO), and anti-human IgE, C3C, C3D and anti-human-fibrinogen within the epidermal spongiotic process, as well as around the blood vessels surrounding the inflammatory process especially at the sweat glands and respective ductus. The patient began mycophenolate mofetil therapy, with successful clearing of the palms and soles. CONCLUSION: The significance of our findings indicates a complex immunological process including complement, MPO and T-cell immune response. In addition, possibly a secondary allergic process for the presence of IgE immune response and possibly aggravation by application of other medicines. Further immunological studies on pompholyx are needed. (Abreu-Velez AM, Pinto FJ, Howard MS. North Am J Med Sci 2009; 1: 117-120). PMID- 22666683 TI - Rebamipide and mosapride enhance pilocarpine-induced salivation. AB - BACKGROUND: During esophageal acid clearance, salivation plays an important role in defending the esophageal mucosa. Mosapride, an agent used in chronic, long term therapy of gastro-esophageal reflux disease (GERD) was regarded as mediating its efficacy through prokinetic properties. Rebamipide is also widely used as an anti-gastritis and anti-ulcer agent in GERD patients with chronic gastritis. The aim of this study is to investigate the effects of rebamipide, mosapride, and risperidone on the salivation induced by pilocarpine. MATERIALS AND METHODS: The experiments were conducted on 4-week male SD rats (120-150g). The salivation was induced by intraperitoneally administrated pilocarpine and saliva was collected using preweighted small cotton balls inserted into the animal's mouth every 30 min for 180 min. Thirteen minutes before intraperitoneal administration of pilocarpine, rebamipide, mosapride, and risperidone were administered intraduodenally. Control rats were conducted by intraperitoneal administration of saline and intraduodenal administration of 0.5% methylcellulose solution. RESULTS: The saliva weight at 0-30 min was significantly (p<0.01) increased after administration of pilocarpine, compared to control rats. An additional administration of mosapride and rebamipide increased the saliva weight at 0-30 min. The total volume of saliva for 150 min after administration of pilocarpine was the highest after preadministration of rebamipide, followed by mosapride, and risperidone. CONCLUSIONS: Increase in salivation produced by i.p. pilocarpine was enhanced by preadministration of rebamipide and mosapride. PMID- 22666684 TI - Demographic shifts in health conditions of adolescents 10-19 years, Jamaica: Using cross-sectional data for 2002 and 2007. AB - BACKGROUND: It is well established in health literature that most adolescents have good health, but this does not mitigate the reality that there are some who are living with chronic and other health conditions. AIMS: To examine the demographic shifts in health conditions and the typology of health conditions experienced by this age cohort. MATERIALS AND METHOD: The current study extracted a sample of 5,229 and 1,394 for adolescents 10-19 years from two surveys collected jointly by the Planning Institute of Jamaica and the Statistical Institute of Jamaica for 2002 and 2007 respectively. The survey was drawn using stratified random sampling. The sample was weighted to reflect the population of the nation. Descriptive statistics and chi-square were used in this study. The level of significance used in this research was 5% (i.e. 95% confidence interval). RESULTS: In 2002, most of respondents had cold (28.3%) and in 2007, this shifted to unspecified health conditions (35.5%). The number of reported cases of arthritis in adolescents was 0.4%, in 2002, which fell by 100% in 2007 whereas increases were observed for unspecified conditions, 42%; hypertension, 175%; and diabetes mellitus, 700%. CONCLUSIONS: There is an immediate need for health promotion and education campaigns geared towards the sensitization of adolescents about the rise in chronic illness, its challenges, lifestyle practices and willingness to seek care if particular symptoms are presently affecting them. PMID- 22666685 TI - Gaucher's disease diagnosed by splenectomy. AB - CONTEXT: Splenectomy continues to find common therapeutic indications for hematologic disorders. In addition, recently it is also performed in surgical clinics to assist diagnose of some illnesses. Gaucher's disease, especially Type I, is the most frequently encountered lysosomal storage disorder in man. Manifestations of it are highly variable. The most frequently found symptoms include splenomegaly with anaemia and thrombocytopenia, mostly due to hypersplenism, hepatomegaly and bone disease. CASES: Four patients were reported in the present study. Three of them were easily diagnosed with Gaucher's disease via bone marrow cytology, and one with Gaucher's disease was detected by pathological examination following the splenectomy. CONCLUSIONS: For the pouse of diagnosis of the Gaucher's disease, performing surgery is generally not necessary. However, for the cases of difficult to diagnose by classical methods, the corect diagnosis of Gaucher's disease can only be made by a special operation. PMID- 22666686 TI - Laboratory evaluations to optimize outcomes of antioxidant nutrition therapy in diabetes management. AB - Medical nutrition therapy (MNT) guidelines acknowledge the need to identify deficiencies of antioxidant vitamins. However, the guidelines contain that such identification is difficult. Thus, there is evidence that available clinical laboratory tests for antioxidant vitamins C and E are not in perspective in clinical practice. Coenzyme-Q(10) and glutathione tests are also available in research laboratories. These indices are invaluable tools for discrete recommendation and monitoring of antioxidant nutrition therapies. This commentary addresses biomarker insight to what the MNT guidelines consider difficult. The importance and limits of the various dietary antioxidants is overviewed. It puts in perspective how clinical laboratory monitoring of vitamins C and E levels can be used to optimize the outcomes of dietary evaluations for diabetes management. Insight to how to interpret the laboratory results is presented. The importance of this commentary is hinged on the premise that the outcome of dietary therapy can be counter-productive when laboratory evaluation or limitations of the antioxidant nutrients are undermined. PMID- 22666687 TI - A public health and suicide risk in Jamaica from 2002 to 2006. AB - BACKGROUND: Globally, suicide is the third leading cause of mortality among persons aged 15-44 years. However in Jamaica it is not among the leading cause of mortality; but its importance cannot be ignored because of this fact. AIMS: This study seeks to 1) update the prevalence of suicide in Jamaica, 2) make comparisons with international data, 3) provide an understanding of age-sex composition of those who are committing suicides, and 4) provide public health practitioners with valuable information which will be used to inform policy decisions. MATERIALS AND METHODS: Secondary data published by the Jamaica Constabulary Force was used for this study. Data were summarized using percentages and associations were examined by Kruskal-Wallis or Analysis of Variance. RESULTS: The suicide rate averaged 2.26 per 100,000 over the last six years. In 2006, the suicide rate for males was 9 times higher than that of females. The group of 65-74 age, among the male population, recorded the highest suicide rate (11.3 per 100,000) and the 5-14 age group recorded the lowest (0.3 per 100,000). The highest rate for the female population (3.4 per 100,000) was recorded in the 65-74 age group. The 30-39 age group showed an overall higher rate of suicide over the study period, this was followed by the 40-49 age group. CONCLUSIONS: Jamaica's suicide rate is among the lowest in the world and in spite of this, there is a need to formulate a suicide policy for the nation in particular males and young adults. PMID- 22666688 TI - Autoimmune pancreatitis. AB - Since the autoimmune pancreatitis was introduced in 1995, it has been recognized as a form of chronic pancreatitis, which is always associated with autoimmune manifestations. As the improvement of technical and instrumental made in ultrasonography, computed tomography and magnetic resonance imaging, the diagnoses of autoimmune pancreatitis is no longer such difficult. Even though the treatment of autoimmune pancreatitis is available with a conservative therapy, there are many points that are still unclearly. These have stimulated widespread interest in this disease from gastroenterologists, endoscopists, pathologists, and prevalent research. The present article provides with our better understanding of the diagnosis and treatment of autoimmune pancreatitis. PMID- 22666689 TI - Computer diagnosis in cardiology. AB - This article reports upon the emergence of a novel cognitive, computer-based technology which may lead to significantly improved methods of cardiological diagnosis and a rapid and inexpensive method of cardiological screening.The technology 'Virtual Scanning' illustrates how, in blood, the reaction of proteins and their reactive substrates releases light; that the colour and intensity of this bioluminescence is unique to each reaction and it's rate; and that the development of pathologies influence cognition and visual perception. This illustrates that the function of the autonomic nervous system is linked to that of the physiological systems and that the rate of biochemical reactions, and the progression of disease, can be measured by a cognitive test procedure and used as an indication of the disease(s) affecting heart function.The article discusses the limitations of the conventional biomarker technique, and the potential value of non-invasive cognitive techniques, such as Virtual Scanning, to the medical practitioner. Finally, it discusses how the ability of Virtual Scanning to diagnose disease from its presymptomatic origins may lead to improved diagnostic accuracy and significantly reduced costs. PMID- 22666690 TI - Childhood health in Jamaica: changing patterns in health conditions of children 0 14 years. AB - BACKGROUND: The new thrust by WHO is healthy life expectancy. Therefore, health must be more than morbidity. It is within this framework that a study on childhood health in Jamaica is of vital importance. AIMS: This study 1) expands the health literature in Jamaica and by extension the Caribbean, 2) will aid public health practitioners with research findings upon which they are able to further improve the quality of life of children, 3) investigates the age at with children in Jamaica become influenced by particular chronic diseases and 4) assesses the subjective wellbeing of children. METHODS: The current study extracted a sample of 8,373 and 2,104 children 0-14 years from two surveys collected jointly by the Planning Institute of Jamaica and the Statistics Institute of Jamaica for 2002 and 2007 respectively. A self-administered questionnaire was used to collect the data. RESULTS: Ninety-one percent of children in Jamaica, for 2007, reported good health. The number of children who had diarrhea fell by 84.2% in 2007 over 2002, and a similar reduction was observed for those with asthma (42.1% in 2002 and 19.7% in 2007). Another critical finding was that 1.2% of children, in 2007, had diabetes mellitus compared to none in 2002. CONCLUSION: Public health now has an epidemiological profile of health conditions of children and the demographic shifts which are occurring and this can be used for effective management and planning of the new health reality of the Jamaican child. PMID- 22666691 TI - A new variant of endemic pemphigus foliaceus in El-Bagre, Colombia: the Hardy Weinberg-Castle law and linked short tandem repeats. AB - BACKGROUND: We reported a new variant of endemic pemphigus foliaceus in El Bagre, Colombia. AIMS: Our study performed Complex Segregation Analysis (CSA) and short tandem repeats to discriminate between environmental and/or genetic factors in this disorder. MATERIALS AND METHODS: The CSA analysis was carried out according to the unified model, implemented using the transmission probabilities implemented in the computer program POINTER, and evaluated by using a software package for population genetic data analysis (GDA), Arlequin. We performed pedigree analyses by using Cyrillic 2.1 software, with a total of 30 families with 50 probands (47 males and 3 females) tested. In parallel to the CSA, we tested for the presence of short tandem repeats from HLA class II, DQ alpha 1, involving the gene locus D6S291 by using the Hardy-Weinberg- Castle law. RESULTS: Our results indicate that the best model of inheritance in this disease is a mixed model, with multifactorial effects within a recessive genotype. Two types of possible segregation patterns were found; one with strong recessive penetrance in families whose phenotype is more Amerindian-like, and another of possible somatic mutations. CONCLUSION: The penetrance of 10% or less in female patients 60 years of age or older indicates that hormones could protect younger females. The greatest risk factor for men being affected by the disorder was the NN genotype. These findings are only possible due to somatic mutations, and/or strong environmental effects. We also found a protective role for two genetic loci (D6S1019 AND D6S439) in the control group. PMID- 22666692 TI - Deposition of immunoreactants in a cutaneous allergic drug reaction. AB - CONTEXT: The analysis of allergic drug reaction pathology may be difficult, especially if multiple histological reaction patterns are detected on review of hematoxylin and eosin (H&E) stained sections. In this case, we emphasize the value of adding immunohistochemistry (IHC) and multicolor direct immunofluorescence (DIF) as tools to improve the diagnosis of these complex disorders. PATIENT AND METHODS: Our patient is a twenty-year-old Caucasian female, who presented with a sudden onset of erythematous macules on the skin following administration of amoxicillin. Lesional tissue was examined by H & E and IHC, and perilesional tissue by DIF and IHC. RESULTS: The H&E findings revealed diffuse dermal edema, and a mild, superficial, perivascular dermatitis with a mixed inflammatory infiltrate, consistent with an allergic drug eruption. The IHC and DIF studies revealed autoreactivity to sweat glands, nerves and dermal blood vessels, as well as dermal deposits of immune reactants such as fibrinogen and complement around the inflamed areas. CONCLUSIONS: Fibrin fibrinogen degradation products have been shown in some cases of allergic disorders; thus, we encourage the effect further testing for these immunoreactants in biopsies from patients with possible allergic drug reactions. PMID- 22666693 TI - Activities of daily living, instrumental activities for daily living and predictors of functional capacity of older men in Jamaica. AB - BACKGROUND: An extensive search of the literature found no studies that have examined functional capacity [Activities of Daily Living (ADL) and Instrumental Activities for Daily Living (I) ADL)] of Jamaican older men as well as factors that determine their functional capacity. AIMS: The current study examines 1) ADL, 2) (I) ADL), 3) self-reported health status, 4) functional capacity, and 5) factors that determine functional capacity of older men. METHODS AND METHOD: Stratified multistage probability sampling technique was used to draw a sample of 2,000 55+ year men. A132-item questionnaire was used to collect the data. Descriptive statistics provide background information on the sample, cross tabulations were used to examine non-metric variables and logistic regression provides a model of predictors of functional capacity. RESULT: Fifty-five percent of sample indicated good current health status. Four percent was mostly satisfied with life; 21.7% had moderate dependence; 77.1% had high dependence (i.e. independence); 1.2% had low dependence; 21.9% were ages 75 years and older; 35.6% were ages 65 to 74 years and 42.6% reported ages 55 to 64 years. Functional capacity can be determined by church attendance (beta=0.245; 95% CI: 0.264, 1.291); social support (beta=0.129; 95% CI: 0.129, 0.258), area of residence (beta=-0.060; 95% CI: -0.427, -0.061) and lastly by age of respondents. CONCLUSION: Ageing in explains deterioration in their (I) ADL, suggesting the challenges of ageing men's independence. More rural men were rarely satisfied with life; but more of them had a greater functional capacity than urban men. Depression was found to negatively relate to functional capacity, and church attendees had a greater functional status than non-attendees. PMID- 22666694 TI - A swallowed sewing needle migrating to the liver. AB - CONTEXT: Swallowing foreign bodies is a common problem in children. Although most objects pass through the gastrointestinal tract with no untoward effect; long, sharppointed, or slender objects can perforate the gut. Migration of a swallowed object to the liver is extremely rare and very few cases have been reported in the literature up to now. The aim of this study is to draw attention to this subject once again by contributing a case report of a child with hepatic migration of a swallowed sewing needle. CASE REPORT: A 16-year-old girl presented to the emergency room of pediatrics department in our hospital with complaints of abdominal pain, nausea and vomiting. Physical examination revealed tenderness on the right upper quadrant of the abdomen. Laboratory examination revealed increased hepatic enzymes as well as increased white blood cell count. Abdominal ultrasonography and computed tomography examinations revealed foreign body in the liver accompanied by surrounding abscess formation. The foreign body (sewing needle) was removed surgically after two operations. CONCLUSION: The children may not be able to remember the swallowing of the foreign body or they may try to hide such a condition. The radiological diagnosis in such cases which can be achieved by X-rays, ultrasonography or computed tomography is of critical importance, as well as getting detailed patient history for foreign body swallowing. PMID- 22666695 TI - Complicated jejunal diverticulosis: A case report with literature review. AB - CONTEXT: Jejunal diverticuli are rare and usually asymptomatic. More commonly, they are seen as incidental findings on CT images, enteroclysis, or during surgery. Complications such as bleeding, perforation, obstruction, malabsorption, diverticulitis, blind loop syndrome, volvulus, and intussusceptions may warrant surgical intervention. CASE REPORT: We report a case of 47-year old woman who had suffered from intestinal obstruction for 3 days. The symptoms did not improve after conservative treatment. An exploratory laparotomy found small bowel obstruction due to proximal jejunal diverticulum with an adhesion epiploic band. Strangulation of the jejunum resulted from the internal hernia caused by the band. The band was removed and the proximal jejunum segmentally resected. The postoperative course was uneventful. CONCLUSION: Although this phenomenon is rare, we should keep in mind that intestinal diverticulosis may induce intestinal obstructions of different kinds, repeat physical examinations and X-ray films are needed and enteroclysis studies or CT scan are helpful in diagnosis. Surgery is indicated for acute abdominal or repeated intestinal obstruction. PMID- 22666696 TI - Expression of integrin alphavbeta6 in the intestinal epithelial cells of patients with inflammatory bowel disease. AB - BACKGROUND AND AIMS: The prevalence of inflammatory bowel disease (IBD) is about 0.05% in industrialized countries. The pathogenesis of IBD remains to be further understood. The present study aims to elucidate the expression of integrin alphavbeta6 in the intestinal mucosa of patients with IBD. MATERIALS AND METHODS: Colonic biopsy was obtained from a group of IBD patients. The expression of alphavbeta6 in the intestinal mucosa was detected by Western blotting. Human colonic epithelial cell line T84 cells were stimulated by microbial antigen flagellin. The expression of alphavbeta6 in T84 cells was evaluated by quantitative RT-PCR and Western blotting. RESULTS: The levels of alphavbeta6 in the intestinal mucosa were much lower than it in normal control subjects. The serum levels of myeloperoxidase (MPO) were higher in IBD patients that were negatively correlated with the levels of alphavbeta6 in the intestinal mucosa. The expression of alphavbeta6 was detectable in T84 cells at naomicronve status that could be upregulated by exposure to microbial antigen flagellin. Pretreatment with MPO dramatically suppressed the expression of alphavbeta6 in T84 cells. CONCLUSIONS: We conclude that the expression of alphavbeta6 was suppressed in IBD intestinal mucosa, which could be resulted from the high levels of MPO. PMID- 22666697 TI - Antigen presenting cells in the skin of a patient with hair loss and systemic lupus erythematosus. AB - CONTEXT: Hair loss is one of the most striking clinical features of active systemic lupus erythematosus (SLE), however, very few studies have investigated the immunological features of this process. CASE REPORT: We describe a 33 years old female who presented with scalp hair loss and arthralgias. Physical examination revealed erythematous plaques on the nose and scalp, with bitemporal hair loss. Scalp biopsies revealed epidermal hyperkeratosis, with a mild interface infiltrate of lymphocytes and histiocytes and a superficial and deep, perivascular and periadnexal infiltrate of mostly CD4 positive cells. Antibodies to HAM 56, CD68, CD1a, S-100, mast cell tryptase and c-kit/CD117 were strongly positive around the hair follicles, and in the adjacent sebaceous glands. CONCLUSION: We present the first report showing a significant presence of several antigen presenting cells around the hair follicular units in a patient with alopecia in active SLE. Today, antigen presenting cells and dendritic cells (DC) are modeled as the master regulators of human immunity. One aspect that has become clearly appreciated is the great diversity of DC subtypes, each with considerable functional differences. Thus, we suggest that APC and DCs are equipped with Pattern Recognition Receptors (PRRs) to some hair follicular unit antigens; that these innate sensors recognize conserved molecular patterns on self- tissue, and play a significant role in the pathophysiology of alopecia in SLE patients. PMID- 22666698 TI - An epidemiological transition of health conditions, and health status of the old old-to-oldest-old in Jamaica: A comparative analysis. AB - BACKGROUND: There is a paucity of information on the old-old-to-oldest-old in Jamaica. In spite of studies on this cohort, there has never been an examination of the epidemiological transition in health condition affect this age cohort. OBJECTIVES: The aims of the current study are 1) provide an epidemiological profile of health conditions affecting Jamaicans 75+ years, 2) examine whether there is an epidemiological transition in health conditions affecting old-old-to oldest-old Jamaicans, 3) evaluate particular demographic characteristics and health conditions of this cohort, 4) assess whether current self-reported illness is strongly correlated with current health status, 5) mean age of those with particular health conditions, 6) model health status and 7) provide valuable information upon which health practitioners and public health specialists can make more informed decisions. METHOD: The current study utilized a sub-sample of approximately 4% from each national cross-sectional survey that was conducted in 2002 and 2007. The sub-sample was 282 people ages 75+ years from the 6,783 respondents surveyed for 2007 and 1,069 people ages 75+ years from the 25,018 respondents surveyed for 2002. RESULTS: In 2007, 44% of old-to-oldest-old Jamaicans were diagnosed with hypertension, which represents a 5% decline over 2002. The number of cases of diabetes mellitus increased over 570% in the studied period. The poor indicated having more health conditions than the poorest 20% of the sample. CONCLUSION: The implications of the shift in health conditions will create a health disparity between 75+ year adults and the rest of the population. PMID- 22666699 TI - Computer diagnosis in cardiology: oxidative stress hypothesis. AB - BACKGROUND: Virtual scanning is one of the emerging technologies in complementary medicine practice. The diagnostic principle is hinged on perception and ultra weak light emission, while the treatment options associated with it includes diet, flash light, exercise and relaxation. However, a mechanism that links the diagnostic and treatment principles has yet to be elucidated. AIMS: The objective here is to further explanation of oxidative stress concept as the biochemical basis of the technology. MATERIALS AND METHODS: Using available literature and basic science textbook, the function of the hypothalamus-pituitary-adrenalin axis as neuro-endocrine physiological system that is strongly linked to the rate of alterations in biochemical processes through to cardiovascular complications is articulated. RESULTS: The hypothesis brings to fore the potential of using the alterations in biochemical processes associated with cognition as tool to validate the Virtual Scanning technology for possible incorporation into clinical practice. Or vice versa to use Virtual Scanning technology to determine the chemiluminescence-related biochemical changes resulting from pathologies that could benefit from relaxation, light therapy, exercise and antioxidant nutrition. CONCLUSIONS: This article advances the applicability of cognitive test procedure for indication of the disease(s) affecting heart function. The implication for some laboratory indices that are already available in clinical practice is highlighted. Investigation of this hypothesis will help provide clear link between plausible mechanism and the theory proposed. PMID- 22666700 TI - Blue 405 nm laser light mediates heart rate - investigations at the acupoint Neiguan (Pe.6) in Chinese adults. AB - BACKGROUND: In previous studies, we showed that laser needle acupuncture with red and infrared light has specific effects on bio-signals of the brain and heart. AIMS: In this publication we report the effect of blue laser light on heart rate and heart rate variability (HRV) before, during and after acupuncture at the acupoint Neiguan (Pe.6) in Chinese adults. These are the first data published concerning heart rate and HRV, obtained with blue laser acupuncture equipment. PATIENTS AND METHODS: The investigations were carried out in 13 healthy Chinese volunteers with a mean age of 31.2 +/- 7.5 years within a randomized, controlled study. Stimulation was performed with painless blue laser light (wavelength: 405 nm; activation: 10 minutes) bilaterally at Pe.6. In a second session, for control reasons the laser was not activated. RESULTS: Heart rate showed a significant (p=0.008) decrease during blue laser light stimulation. In contrast, no significant changes were found when the laser was deactivated. The evaluation parameter LF/HF ratio (low frequency/high frequency ratio) from the HRV spectral analysis showed a very slight increase during stimulation, however it was not significant. CONCLUSIONS: Our main conclusion is that continuous blue laser light stimulation on Neiguan significantly reduces heart rate of Chinese adults. PMID- 22666701 TI - The validity of using self-reported illness to measure objective health. AB - BACKGROUND: There is a longstanding discourse on whether self-reported health is a good measure of objective health. This has never been empirical examined in Jamaica. AIMS: Study seeks to 1) examine the relationship between particular subjective and objective indexes; 2) investigate the validity of a 4-week subjective index in measuring objective indexes; 3) evaluate the differences that exist between the measurement of subjective and objective indexes by the sexes; and 4) provide policy makers, other researchers, public health practitioners as well as social workers with research information with which can be used to inform their directions. MATERIALS AND METHODS: Data published by the Statistical Institute of Jamaica, and the Planning Institute of Jamaica and the Statistical Institute of Jamaica were used for this study. Descriptive statistics were used to provide background information on data. Scatter diagrams were employed to establish 1) statistical associations, and 2) linearity and non-linearity between variables under examination. Multiple regression, using the enter method, was employed to a predictive model of linear associations. RESULTS: A strong significant association was found between life expectancy at birth for the Jamaican population and self-reported illness (r = -0.731); and this was weaker females (r = - 0.683) than males (r = - 0.796). However, the relationship between mortality and self-reported illness was a weak non-linear one. CONCLUSIONS: Self reported illness in a 4-week reference period is a good measure of objective health and that self-reported illness for males was a better measure for objective health than for females. PMID- 22666702 TI - Influence of chronic ethanol consumption on extra-pancreatic secretory function in rat. AB - BACKGROUND: The usefulness of the typical direct methods involving duodenal intubation, such as the secretin and secretin-cholecystokinin tests, in the diagnosis of exocrine pancreatic dysfunction is widely accepted. However, these diagnostic tests tend to be avoided because of their technical complexity and the burden on patients. Recently, a simple breath test was developed for assessment of exocrine pancreatic function employing 13C-dipeptide [i.e., benzoyl-L-tyrosyl [1-13C] alanine (Bz-Tyr-Ala)]. Although alcohol abuse causes pancreatic damage in humans, this has been unclear in rats. AIMS: The aim of the study is to evaluate the effect of ethanol exposure beginning at an early age on extra-pancreatic secretory function in rats. MATERIALS AND METHODS: Twelve female rats of the F344 strain aged 12 months were used. Seven rats were fed on a commercial mash food with 16% ethanol solution (Japanese Sake) as drinking-fluid since at 29 days of age (ethanol group). The remaining five rats were fed on a nutrient-matched isocaloric diet with water as drinking-fluid (control group). After 24-hr fasting, rats are orally administrated 1cc of water containing sodium 13C dipeptide (5 mg/kg) and housed in an animal chamber. The expired air in the chamber is collected in a breath-sampling bag using a tube and aspiration pump. The 13CO2 concentration is measured using an infrared spectrometer at 10-min interval for 120 min and expressed as delta per mil. RESULTS: The breath 13CO2 level increased and peaked at 20 min in both two groups. In general, 13CO2 excretion peaked rapidly and also decreased sooner in ethanol rats than in control rats. The mean value of the maximal 13CO2 excretion is 34.7 per mil in ethanol rats, greater than in control rats (31.4 per mil), but the difference did not reach the statistically significance. CONCLUSION: Chronic ethanol feeding beginning at an early age does not affect extra-pancreatic secretory function in rats. PMID- 22666703 TI - Evaluation of lithium determination in three analyzers: flame emission, flame atomic absorption spectroscopy and ion selective electrode. AB - BACKGROUND: Lithium carbonate salt has become an increasingly important substance in the treatment of manic depressive disorders, and its relatively narrow therapeutic range has caused laboratories to monitor the serum concentration carefully. In the present work we evaluated lithium measurement in 3 different analyzers. METHODS #ENTITYSTARTX00026; MATERIALS: Three different analyzers including Flame Emission (FES), Flame Atomic Absorption Spectroscopy (FAAS), and Ion Selective Electrode (ISE) were used. All chemicals had a grade suitable for trace metal analysis. RESULTS: Within-day precision of CV was <= 1.5% for FES & FAAS, except for ISE (1.9% CV). Between-days precision of CV was less for FES than for FAAS and ISE (1.3% versus 2.2% & 2.3%). The percent recovery of added lithium in pooled patients' serum was higher for ISE than for FASS and FES (103.4% versus 96.2% and 94.6%). We also obtained a higher average lithium concentration for patients' serum samples (n=16) measured by ISE than for FAAS and FES (0.825+/-0.30 versus 0.704+/-0.26 & 0.735+/-0.19). Paired t-test results revealed a significant difference (p< 0.001) for patient sera analyzed with FAAS and ISE. CONCLUSION: We report higher results for ISE than the other two analyzers and conclude that the choice between the two flame methods for patients' serum lithium determination is arbitrary and that FES analyzer is a more attractive routine alternative for lithium determination than FAAS because of its cost and ease of performance. In addition, the results obtained by ISE are precise. However, its accuracy may depend on other interfering factors. PMID- 22666704 TI - Access to contraception by minors in Jamaica: a public health concern. AB - BACKGROUND: Access to contraceptive by minors (pre-adolescents and adolescents) has spurred policy and legislative debates, part of which is that in an effort to successfully meet government's objective of a healthy sexual lifestyle among minors. AIMS: THIS STUDY EXAMINED FACTORS AFFECTING SEXUAL REPRODUCTIVE HEALTH IN MINORS, NAMELY: access to contraceptive advice and treatment, pregnancy, number of sexual partners, sexually transmitted infections (STIs) and confidentiality. MATERIALS AND METHODS: This research involved quantitative and qualitative data. Two hundred and thirty eight sexually active cases were investigated in Jamaica by the researchers, during the period 2006-2007. The age group population was 9 11, 12-14, and 15-17. RESULTS: The study showed that access to contraceptive advice and treatment by minors was more favorable to males than females. The difference in access to contraceptive between male and female was statistically significant (x(2) = 20.16, p<0.05). Of the 80 male respondents, who are contraceptive users, 11 encountered challenges in legitimately accessing contraceptive methods, while 38 of the 40 female users also encountered challenges. This resulted in unintended pregnancies and impregnation (33.2%), as well as the contracting of STIs (21%). CONCLUSION: The findings of this study will be important in informing the development of reproductive health services and family life education programs for pre-adolescents and adolescents in Jamaica and other Caribbean countries. PMID- 22666705 TI - Examining health status of women in rural, peri-urban and urban areas in Jamaica. AB - BACKGROUND: A comprehensive review of the literature revealed that less information is available in literature on health status of women, and health status of women in 3 geographical zones in Jamaica. AIMS: This study examined data on the health status of women in Jamaica in order to provide some scientific explanation of those factors that account for their health status; and differences based on area of residence. MATERIALS AND METHODS: The sub-sample for the current study was 8,541 women ages of 15 and 100 years extracted from a national survey of 25,018 respondents. Stratified random sampling technique was used to draw the sample. Data were stored, retrieved and analyzed using SPSS 16.0. Descriptive statistics were used to provide background information on the subsample, and logistic regressions were utilized to model health statuses. RESULTS: Rural women had the lowest health status (OR = 0.819, 95% CI = 0.679 0.989) among all women (peri-urban OR = 1.054, 95% CI = 0.842-1.320; urban OR = 1.00) and that they were the least likely to have health insurance coverage. Health insurance was the critical predictor of good health status of women in Jamaica, and this was equally the same across the 3 geographic areas; and that married women were 1.3 times more likely (OR 1.3, 95 CI = 1.036-1.501) to report good health compared to those who were never married. CONCLUSION: This study provides an understanding of women's health status in Jamaica as well as the disparity which correlates based on the different geographical regions. PMID- 22666706 TI - Health of females in Jamaica: using two cross-sectional surveys. AB - BACKGROUND: The 21(st) Century cannot see the examination of health status of elderly, population, children and adolescents; but not for females. AIMS: current study are 1) to examine the health conditions; 2) provide an epidemiological profile of changing health conditions in the last one half decade (2002-2007); 3) evaluate whether self-reported illness is a good measure of health status; 4) compute the mean age of females having particular health conditions; 5) calculate the mean age of being ill compared with those who are not ill; and 6) assess the correlation between health status and income quintile. METHODS AND RESULTS: In 2002, a subsample of 12,675 females was extracted from the sample of 25,018 respondents and for 2007; a subsample of 3,479 females was extracted from 6,783 respondents. RESULTS: There is reduction in the mean age of females reported being diagnosed with chronic illness such as diabetes mellitus (60.54 +/- 17.14 years); hypertension (60.85 +/- 16.93 years) and arthritis 59.72 +/- 15.41 years). The greatest decline in mean age of chronically ill diagnosed females was in arthritic cases (by 7.41 years). Concurrently, the mean age of females with unspecified health conditions fell by (33%, from 54.62 +/- 21.77 years in 2002 to 36.42 +/- 23.69 years in 2007). CONCLUSION: Although healthy life expectancy for females at birth in Jamaica was 66 years, improvements in their health status cannot be neglected as there are shits in health conditions (to diabetes mellitus) as well as the decline in ages at which females are being diagnosed with particular chronic illnesses. PMID- 22666707 TI - Response of patients to the introduction of a private Magnetic Resonance Imaging service in Western Jamaica. AB - BACKGROUND: Magnetic Resonance Imaging (MRI) is one of today's fastest growing imaging modalities, spurred in part by rapid advances in technology and important new applications in patient care. It was introduced in Western Jamaica in March 2005 at a non-hospital-based facility called North Coast Imaging MRI Service. AIMS: The study examined the socio-demographics, accessibility and affordability of the services to patients. MATERIALS AND METHOD: A random sample of 100 patients was used and the research instrument was a questionnaire. The study was conducted between August and November 2008. RESULTS: The findings of the study showed that majority of the respondents lived in rural areas and were within the age group 30 - 59 years. One-half of the respondents resided in St. James, were employed; earned more than US$1,351.00 per month and could afford the cost of the MRI procedure. More than one half of the respondents indicated that it took 15 - 30 minutes to be examined after arrival at the Centre; most (81%) of the respondents indicated that the MRI procedure was adequately explained, and 99% indicated that questions about the procedure were satisfactorily answered. The MRI Scans performed at the North Coast Imaging MRI Service showed an increase of 157.49% in 2006 when compared with 2005, and 70.90% in 2007 when compared with 2006. Our findings suggest that the number of MRI scans done at the North Coast Imaging MRI Service is likely to increase. CONCLUSION: Although most of the respondents were able to afford the procedure there are concerns about persons in the lower socio-economic group who are unable to afford expensive diagnostic imaging tests such as MRI scans. There is an urgent need for government-owned hospital-based MRI Units in Jamaica to offer lower cost MRI scans to the public. PMID- 22666708 TI - Solitary fibrous tumor with giant multinucleated cells in the retroperitoneum - a case report. AB - CONTEXT: Solitary fibrous tumor is a distinct neoplasm, rarely recognized in extrathoracic sites. CASE REPORT: The article reports a new case in the retroperitoneum in a 55 year-old man, who presented with urinary symptoms. Tumor was completely excised, and the solitary fibrous tumor was diagnosed after pathologic examination and immunohistochemistry. The patient has remained free of disease for five years since surgery. CONCLUSION: An uncommon variant of retroperitoneal solitary fibrous tumor with giant multinucleated cells was documented in the study. PMID- 22666709 TI - Management of stress and stress-related diseases: Emerging computer-based technologies and the rationale for clinical laboratory assessment. AB - BACKGROUND: Over the years, the issue of stress management in mental health has been discussed without reference to the clinical laboratory perspectives. Translational research and the vast array of emerging diagnostic technologies in alternative medical practice are now bridging the gap. While it would be scientific arrogance for the clinical practitioner and scientist to ignore the trend, the new technologies seeking clinical acceptability necessarily require expatiation of the scientific aspects of their products. AIMS: This commentary builds on a comparative critical review to further our hypothesis that oxidative stress is the biochemical basis of the emerging computer-based diagnostic technologies. MATERIALS #ENTITYSTARTX00026; METHOD: The available information on Computer Meridian Diagnostics, Neuropattern and Virtual Scanning technologies were critically reviewed. The differences and similarities were articulated. RESULTS: The technologies seem different, but have similarities that have not been articulated before. The seemingly different theories are traceable to Russian scientists and are based upon stress-induced adrenal secretions and the associated effect on glucose metabolism. The therapeutic effects of antioxidant nutrition, exercise or relaxation that are inherent in the technologies are highlighted. CONCLUSION: This commentary furthers explanation of the alterations in antioxidant activities as a result of biofeedback, oxidative stress and/or physiological effects as the biochemical basis of the technologies. The place for antioxidant indices and whole blood viscosity are also highlighted. This provides a rationale for the evaluation of available clinical diagnostic tests both to validate the technologies and as clinical laboratory correlates in stress management. PMID- 22666710 TI - Dichotomising poor self-reported health status: Using secondary cross-sectional survey data for Jamaica. AB - BACKGROUND: Caribbean scholars continue to dichotomise self-reported health status without empirical justification for inclusion or exclusion of moderate health status in the dichotomisation of poor health. AIMS: This study will 1) evaluate which cut-off point should be used for self-reported health status; 2) assess whether dichotomisation of self-reported data should be practiced; 3) ascertain any disparity in dichotomisation by some covariates (i.e., marital status, age cohort, social class); and 4) examine the odds of reporting poor or moderate-to-very poor self-reported health status if one has an illness. MATERIALS AND METHODS: The current study used cross-sectional survey data for 2007. The survey used stratified probability sampling techniques to collect the data from Jamaicans. The sample consisted of 6,783 respondents, with a focus on participants aged 46+ years (n=1,583 respondents). Self-reported health status was a 5-item Likert scale question. The dichotomisation was poor health status or otherwise and poor (including moderate) self-reported health. Odds ratios were calculated in order to estimate the effect of the covariates. RESULT: When moderate self-reported health status was used in poor health status, the cut-off revealed moderate effect on specified covariates across the age cohorts for women. However, for men, exponential effects were used on social class, but not on area of residence or marital status across the different age cohorts. CONCLUSIONS: The cut-off point in the dichotomisation of self-reported health status does not make a difference for women and must be taken into consideration in the use of self-reported health data for Jamaica. PMID- 22666711 TI - Ptyalism gravidarum. AB - CONTEXT: Ptyalism gravidarum is of unknown origin and is usually defined as an excessive secretion of saliva, common in women with nausea and vomiting who might have difficulty in swallowing their saliva. CASE REPORT: We present here 2 cases complicated by ptyalism gravidarum during all trimesters of pregnancy. In one case, ptyalism recovered spontaneously at 35-36 weeks' gestation, and in the other case, it recovered after delivery. CONCLUSION: Ptyalism gravidarum may not be a serious condition leading to adverse perinatal outcomes, however there may not be any satisfactory treatment. PMID- 22666712 TI - Hepatic metastases of primary jejunal carcinoid tumor: A case report with radiological findings. AB - CONTEXT: Carcinoid tumors represent a group of well-differentiated tumors originating from the diffuse endocrine system outside the pancreas and thyroid. The overall prevalence of carcinoid tumors in the United States is estimated to be one to two cases per 100,000 persons. Various sites of origin of this neoplasm are appendix - 30-45%, small bowel - 25-35% (duodenum 2%, jejunum 7%, ileum 91%, multiple sites 15-35%), rectum 10-15%, caecum - 5%, and stomach - 0.5%. Liver metastases from jejunal and ileal carcinoids are generally hypervascular. CASE REPORT: Here we report a case of primary jejunal carcinoid tumor in a 66-year-old woman metastasizing to liver with ultrasonography, computed tomography, and diffusion-weighted magnetic resonance imaging (DWI) findings. CONCLUSION: Primary jejunal carcinoid tumor is a rare entity. DWI can help in the differential diagnosis of hepatic hypervascular metastatic mass lesions from benign ones, as well as in the diagnosis of carcinoid tumor. PMID- 22666713 TI - Presence of neutrophil extracellular traps and antineutrophil cytoplasmic antibodies associated with vasculitides. AB - CONTEXT: Anti-neutrophil p-ANCA antibodies are directed against antigens in the peripheral cytoplasm of both neutrophilic granulocytes and monocytes. They are detected in several autoimmune disorders and are particularly associated with systemic vasculitis. CASE REPORT: We report a case of a 54-year-old female presenting with a pruritic rash, including purpura and diffuse erythema. A biopsy with hematoxylin and eosin (H & E) analysis, direct immunofluorescence (DIF), immunohistochemistry (IHC) and enzyme-linked immunosorbent assays for ANCAs were performed. The H & E staining demonstrated leukocytoclastic vasculitis, with focal vascular fibrinoid necrosis. The DIF revealed evidence of vasculitis, the presence of p-ANCAs and neutrophil extracellular traps (NETs). The IHC displayed autoreactivity to myeloperoxidase within the vessels. The IHC aided in ruling out any intrinsic autofluorescence of the vessels. CONCLUSIONS: By observing the deposition of neutrophil extracellular traps and myeloperoxidase in inflamed skin vessels, biopsy analysis may alert physicians for rapid therapeutic intervention in patients presenting with possible vasculitides. PMID- 22666714 TI - Accessory mental foramen. AB - CONTEXT: Accessory mental foramen is a rare anatomical variation. Even so, in order to avoid neurovascular complications, particular attention should be paid to the possible occurrence of one or more accessory mental foramen during surgical procedures involving the mandible. CASE REPORT: A 3-dimensional computed tomography (3D-CT) scan of a female patient revealed an accessory mental foramen on the right side of her mandible. CONCLUSION: A 3D-CT scan should be obtained prior to mandibular surgeries so that the presence of accessory mental foramen can be detected, and so that the occurrence of a neurosensory disturbance or hemorrhage can be avoided. Although this anatomical variation is rare, it should be kept in mind that an accessory mental foramen may exist. PMID- 22666715 TI - Axillary pilonidal sinus: A case report. AB - CONTEXT: Pilonidal sinus is a disease which is very common, especially in men and usually located in sacrococcygeal area. However, the disease can be also seen in rare localizations such as umblicus, forehead, scalp, clitoris, interdigital area and axilla. In the etiology of pilonidal sinus, acquired theory is accepted by most of surgeons instead of the congenital one. CASE REPORT: In the present study, we purposed to report our case of hirsute Turkish women aged 25 having axillary pilonidal sinus. After application of total surgical excision with eliptical skin incision, histopathological evaluations confirmed the prediagnosis of axillary pilonidal sinus. The patient was lost to follow-up and neither recurrens nor distance metastasis has been detected during 36 months. CONCLUSIONS: In our opinion; surgical therapy of axillary pilonidal sinus, allows to complete resection in addition to absolute histopathological diagnoses and it may be an appropriate choice of treatment especially for the disease having one or two sinuses. PMID- 22666716 TI - Giant cell tumor of soft tissue of neck: a case report. AB - CONTEXT: Giant cell tumor of soft tissue is a rare primary soft tissue tumor with low malignant potential. It is clinically and pathologically similar to the giant cell tumor of the bone. CASE REPORT: We report a case of a 28-year-old man complaining of a painless solitary nodule arising in the spinal muscle of the neck. Computed tomography suggested a neurogenic tumor, but the diagnosis of giant cell tumor was confirmed after detailed pathological examination. The patient remains disease free five months after diagnosis. CONCLUSION: It is important to recognize this pathological entity in order to avoid misdiagnosis with other fibrous tumors associated with giant cells. PMID- 22666717 TI - Clear cell adenocarcinoma of a female urethra: A case report and review of the literature. AB - CONTEXT: Clear cell adenocarcinoma of the urethra is an extremely rare tumour. Its histogenetic derivation remains controversial. CASE REPORT: We report a new case of clear cell adenocarcinoma of the proximal urethra in a 56-year-old woman who presented with grossly hematuria. Urethral cystoscopy revealed a tumour protruding from the posterior urethral wall at the bladder neck. Treatment consisted of urethrocystectomy with pelvic lymph node dissection. Histologically, the neoplasm consisted of clear cell adenocarcinoma of the urethra. CONCLUSION: It appears that female urethral adenocarcinoma has more than one tissue of origin. PMID- 22666718 TI - Gastrointestinal stromal tumor of the pancreas: A case report and review of the literature. AB - CONTEXT: Primary stromal tumors of the pancreas are extremely rare. Only four cases have been reported in the literature. We describe a new case and analyze, through a review of the literature, the clinical and pathological data, and the outcome of the previously reported cases. CASE REPORT: We report the case of a 52 year-old-woman who presented with epigastric pain. Preoperatively, abdominal pelvic computed tomography revealed a pancreatic head mass. The surgery confirmed the presence of a large tumor of the pancreatic head. Pathologic results revealed a malignant gastrointestinal stromal tumor of the pancreatic head, completely removed. There is no recurrence or metastases 10 months after surgery. CONCLUSION: The current case consolidates the possibility that this rare tumor can involve the pancreas as a primary site and that GIST of primary pancreatic localization are usually of high risk of malignancy. PMID- 22666719 TI - Association of cardiac ausculatory findings with coronary heart disease mortality. AB - BACKGROUND: Relationships between cardiac murmurs detected during physical examination and coronary heart disease mortality among the general population are not well described. AIMS: To assess the relationship between cardiac murmurs detected during physical examination and coronary heart disease mortality. METHODS AND RESULTS: This relationship was examined with Cox regression analyses of data from 7990 adults, aged 30-75 years, from the Second National Health and Nutrition Examination Survey Mortality Study (1976-1992). Covariates included age, race, sex, history of CVD, diabetes, probable left ventricular hypertrophy, serum cholesterol, body mass index, blood pressure, and smoking status. During 16.8 follow-up years , there were 457 deaths from coronary heart disease (CHD) (ICD-9 410-414) and 661 deaths from diseases of the heart (ICD-9 390-398, 402, 404, 410-414, 415-417, 420-429). A systolic murmur was present in 420 persons and a diastolic murmur was present in 56 persons at baseline. Persons with a heart murmur were at increased risk of death from CHD (relative risk=1.7, 95% confidence interval=1.2, 2.5) and from diseases of the heart (RR=2.2, 95% CI=1.6, 2.9) after multivariate adjustment for cardiovascular disease risk factors. Similar results were observed when murmur intensity (i.e., murmur grade) was accounted for. CONCLUSIONS: These results suggest that the presence of a heart murmur may be associated with an increased risk for mortality from both CHD and diseases of the heart. PMID- 22666720 TI - Early chest tube removal after coronary artery bypass graft surgery. AB - BACKGROUND: There is no clear data about the optimum time for chest tube removal after coronary artery bypass surgery. AIM: The aim of this study was to assess the impact of the chest tube removal time following coronary artery bypass grafting surgery on the clinical outcome of the patients. MATERIAL AND METHODS: An analysis of data from 307 patients was performed. The patients were randomized into two groups: in group 1 (N=107) chest tubes were removed within the first 24 hours after surgery, whereas in group 2 (N=200), chest tubes were removed in the second 24 hours after surgery. Demographics, lactate and pH at the beginning, during and after the operation, creatinine, left ventricular ejection fraction, inotropic drugs administration, length of ICU stay, and mortality data were collected. Respiratory rate and pain level was assessed. RESULTS: In these surgeries, the mean+/- standard deviation for the aortic clamping time was 49.18+/-17.59 minutes and cardiopulmonary bypass time was 78.39+/-25.12 minutes. The amount of heparin consumed by the second group was higher (P <0.001) which could be considered as an important factor in increasing the drainage time after the surgery (P =0.047). The pain level evaluated 24 hours post-operation was lower in the first group, and the difference in the pain level between the 2 groups evaluated 30 hours post-operation was significant (P=0.016). The mean time of intensive care unit stay was longer in the second group but it was not statistically significant. CONCLUSION: Early extracting of chest tubes after coronary artery bypass graft surgery when there is no significant drainage can lead to pain reduction and consuming oxygen is an effective measure after surgery toward healing; it doesn't increase the risk of creation of plural effusion and pericardial effusion. PMID- 22666721 TI - Alternate electrification and non-potable water: A health concern for Jamaicans. AB - BACKGROUND: Research has shown that the absence of electricity and potable water usually result in negative effects on one's health and is more likely to affect women than men. AIM: To determine the extent to which alternate electrification and limited potable water, impacts on health. MATERIALS AND METHOD: This study is informed by primary and secondary data, representing a sample size of 150 respondents (75 male and 75 female), who were interviewed via a 24-item structured interview schedule during the period 2006-2007, throughout the 14 parishes of Jamaica. In an effort to determine the number of persons to be interviewed, each parish population was divided by the island's population (2,599,334) and then multiplied by 150. Data was analyzed using the statistical package for social scientists 15. RESULTS: The respondents of this study who use kerosene lamp as an alternate means to electricity use firewood for cooking (12% male and 15% female). This sometimes result in obstructive pulmonary disease (female 43%; male 21%). The absence of electricity also results in the consumption of improperly stored meat, thus medical implications: paroxysmal abdominal pain (colic), and diarrhea (male 91%; female, 95%). The transporting of firewood, pans of water and laundry via head-loading, sometimes result in back/spinal injury (male, 75%; female, 48%). CONCLUSION: Alternate access to electricity and potable water result in the use of kerosene lamp, firewood and the consumption of non-potable water (often transported on one's head) - causing medical implications such as back/spinal injury, obstructive pulmonary disease, paroxysmal abdominal pain and gastroenteritis. PMID- 22666722 TI - Self-rated health and health conditions of married and unmarried men in Jamaica. AB - BACKGROUND: Since 1988, when Jamaica began collecting data on the living conditions of its people, men have reported seeking less health care than women. Despite this fact, the group has never been studied by researchers. The same is true about the health status of married and non-married men. OBJECTIVES: The current study will 1) evaluate the changing epidemiological patterns of diseases affecting men in Jamaica; 2) determine factors that correlate with good health status of men; 3) compare and contrast the differences in health status of men, in particular marital status; and 4) determine which marital status has the greater health status. MATERIALS AND METHODS: The data for this research were taken from two secondary cross-sectional surveys. A sample of 8,078 respondents 15 years and older was extracted from the 2002 survey (n=25,018 respondents) and 2,224 respondents from the 2007 sample (n=6,783 respondents). SPSS for Windows 16.0 was used to store, retrieve and analyse the data. Chi-square, analysis of variance, t-test and logistic regression were used in this paper. RESULTS: Married men are more likely to report an illness than never married (OR = 1.68, 95% CI = 1.45-1.95), separated, divorced or widowed men (OR = 2.62, 95% CI = 2.06 3.33). No significant statistical difference existed between the self-rated health status of married and unmarried men. CONCLUSION: This study provides a platform upon which future studies can commence as we begin to examine men's health in Jamaica. PMID- 22666723 TI - Seroepidemiology of Bordetella pertussis infections in the twin cities of Pakistan. AB - BACKGROUND: Bordetella pertussis is the cause of whooping cough occurring mainly in children. The prevalence of this disease has been reduced largely due to worldwide mass vaccination with DTP vaccine. However, the immunity produced by the vaccination wanes by the passage of time. Still this disease kills around 2-4 million children annually. Adults may be a source of infection for infants and children. Furthermore, Bordetella pertussis has also been found to be associated with cases of persistent cough in adults in many countries. AIM: The aim of this study was to study the exposure of the adult population to the Bordetella pertussis by detecting IgG antibodies. MATERIALS AND METHODS: We performed Seroepidemiology of Bordetella pertussis infections in multiethnic twin cities of Pakistan (Rawalpindi and Islamabad) using a commercially available ELISA kit to have a picture of epidemiology of Bordetella pertussis in Pakistan. We targeted adults of age between 18-45 years (mean age 29.64 years). RESULTS: The results of our study show a high percentage of seropositivity to Bordetella pertussis (89 percent), which indicates higher exposure to this organism and risk of infection to infants, children, adolescents and adults. CONCLUSION: A high percentage of seropositive individuals are alarming to health care professionals as well as policy makers. Bordetella pertussis infections may be associated with their atypical manifestation in Pakistan. Adult vaccination with DTP is recommended to reduce the risk of infection in infants and children through adult reservoirs. PMID- 22666724 TI - Health status of patients with self-reported chronic diseases in Jamaica. AB - BACKGROUND: Developing countries such as Jamaica suffer increasingly from high levels of public health problems related to chronic diseases. AIMS: To examine the physical health status and use a model to determine the significant predictors of poor health status of Jamaicans who reported being diagnosed with a chronic non-communicable disease. METHODS AND MATERIALS: The current study extracted a sub-sample of 714 people from a larger nationally representative cross-sectional survey of 6,783 Jamaicans. A self-administered questionnaire was used to collect the data from the sample. Statistical analysis was performed using chi-square to investigate non-metric variables, and logistic regression to determine predictors of poor health status. RESULTS: Approximately one-quarter 25.3%) of the sample reported that they had poor health status. Thirty-three percent of the sample indicated unspecified chronic diseases: 7.8% arthritis, 28.9% hypertension, 17.2% diabetes mellitus and 13.3% asthma. Asthma affected 47.2% of children and 23.2% of young adults. S ignificant predictors of poor health status of Jamaicans who reported being diagnosed with chronic diseases were: age of respondents, area of residence and inability to work. CONCLUSION: Majority of the respondents in the sample had good health, and adults with poor health status were more likely to report having hypertension followed by diabetes mellitus and arthritis, while asthma was the most prevalent among children. Improvement in chronic disease control and health status can be achieved with improved patient education on the importance of compliance, access to more effective medication and development of support groups among chronic disease patients. PMID- 22666725 TI - Determinants of quality of life of youths in an English-speaking Caribbean nation. AB - BACKGROUND: Studies on quality of life (QoL) on youths are limited and have not examined determinants of QoL for this cohort. AIMS: The current study seeks to examine the QoL of Jamaican youths and to build a model that identifies factors that explain QoL. MATERIALS AND METHOD: During the period June to August 2006, the Centre of Leadership and Governance, Department of Government, at the University of the West Indies, Mona Campus, conducted a stratified random probability survey of 1,338 respondents. Data were collected using a 166-item questionnaire. Of the sampled population (N=1,338), the proportion of those respondents age 18 to 25 years was 27% (N=364) and this constitutes the sample for the current study. The data were stored and retrieved in the Statistical Package for the Social Sciences (SPSS 12). Descriptive statistics were used to analyse the data, and logistic regression was used to establish the model. RESULTS: The quality of life of Jamaican youths was determined by 4 factors which explain 20% of the variability in quality of life. The parents' economic wellbeing has the most influence on the quality of life of Jamaican youths (OR=1.348; 95% CI: 1.35, 3.04), followed by moderate religiosity (OR=3.594; 95% CI: 1.47, 8.82), the extent of the welfarism of the state (OR=5.273; 95% CI: 1.04, 1.69) and gender (OR = 1.329, 95% CI = 1.04, 1.69). CONCLUSION: The current work has offered us an understanding of the determinants of QoL of youths and how interventions can be planned for in the future. PMID- 22666726 TI - Metastatic hidradenocarcinoma: Surgery and chemotherapy. AB - CONTEXT: Hidradenocarcinoma is a rare carcinoma of high malignant potential. It most metastasizes to regional lymph nodes and distant viscera. CASE REPORT: We report a case of 52-year-old woman who presented with an invasive hidradenocarcinoma of the finger, treated with surgical excision. The patient presented with skin and lymph node metastases four years after, treated by chemotherapy. CONCLUSION: Hidradenocarcinoma is an aggressive tumor. It seems important to use adjuvant therapies particularly for recurrent and metastatic forms. PMID- 22666727 TI - Lymphoepithelioma - like carcinoma of the bladder in a North African man: A case report. AB - CONTEXT: Lymphoepithelioma - like carcinoma of the bladder is an extremely rare tumour. We discuss through a new case and a review of the literature the pathological pattern and the management of this uncommon entity. CASE REPORT: We report the case of a 58 year-old man who presented with a macroscopic hematuria. Transurethral bladder resection was consistent with the diagnostic of a poorly differentiated carcinoma infiltrating the bladder's muscle. A radical cysto prostatectomy was performed. The pathological examination revealed an EBV negative lymphoepithelioma-like carcinoma of the bladder. CONCLUSION: Lymphoepithelioma-like carcinoma of the bladder is a rare bladder cancer that is important to recognize since it has a favourable prognosis. PMID- 22666728 TI - Familial early onset of type-2 diabetes mellitus and its complications. AB - BACKGROUND: Globally, the prevalence of chronic, non-communicable diseases is increasing at an alarming rate. Furthermore, approximately 197 million people worldwide have impaired glucose tolerance. Consequently, diabetes is rapidly emerging as a global health problem that threatens to assume a pandemic level by 2030. In Indian population, genetic predisposition to trigger diabetes at an early age as compared to western counterpart has been focused very much. AIM: To gain further insight into the positive correlation between the diabetes and family history was the objective of this study. MATERIALS AND METHODS: Patients attending the Diabetes Centre, K.L.E.S Dr. Prabhakar. Kore Hospital and Medical Research Centre; J. N. Medical College; KLE University Belgaum, Karnataka- India, were recruited, diagnosed and analyzed as per WHO criteria. RESULTS: The prevalence of diabetes was higher among patients with diabetic mother (25.6%) compared to patients with diabetic father (21.2%) and there was early onset of type -2 diabetes among patients having both parents with diabetic when compared to other patients. CONCLUSION: Based on the present observation, it would be appropriate to emphasize again that a strong family history for diabetes, would signal at an early age, the onset of diabetes perhaps with its complications. PMID- 22666729 TI - Endocrine disturbances related to the use of lithium. AB - Despite recent advances in pharmacological treatment of psychiatric disorders, lithium salts remain frequently used, as they are effective and inexpensive alternatives, especially in the treatment of bipolar disorders. Their use is commonly associated with various endocrine disorders, mainly in thyroid and parathyroid function, and in mineral metabolism. This article aims at reviewing these potential endocrinopathies related to the use of lithium to make health care professionals aware and familiar with these possible complications when they follow up patients using this drug, and to make them able to monitor, identify and institute early and appropriate treatment. PMID- 22666730 TI - [Assessment of the hypothalamic-pituitary-adrenal axis in Cushing's disease diagnosis and remission]. AB - Cushing's disease (CD) remains a medical challenge, with many questions still unanswered. Successful treatment of CD patients is closely related to correct approach to syndromic and etiological diagnosis, besides the experience and talent of the neurosurgeon. Pituitary transsphenoidal adenomectomy is the treatment of choice for DC. Assessment of remission after surgery and recurrence in the long term is an even greater challenge. In this regard, special attention should be paid to the role of postoperative serum cortisol as a marker of CD remission. Additionally, the postoperative use of exogenous glucocorticoids only in cases of adrenal insufficiency has been suggested by some authors as an essential practice to enable the use of serum cortisol in this scenario. In this article, we review the forms of evaluation of DC activity, and markers of remission and relapse of CD after transsphenoidal surgery. PMID- 22666731 TI - Parathyroid hormone: an early predictor of symptomatic hypocalcemia after total thyroidectomy. AB - OBJECTIVE: The purpose of this study was to evaluate if the measurement of peri operative parathyroid hormone (PTH) is able to identify patients with increased risk of developing symptoms of hypocalcemia. SUBJECTS AND METHODS: Forty patients who underwent total thyroidectomy were studied prospectively. Ionized serum calcium and PTH were measured after induction of anesthesia, one hour (PTH1) and one day after surgery (PTH24). Patients were evaluated for symptoms of hypocalcemia and treated with calcium and vitamin D supplementation as necessary. RESULTS: Symptomatic hypocalcemia developed in 16 patients. Symptomatic patients had significant lower PTH1 and greater drops in PTH levels. The selection of 12.1 ng/L as PTH1 level cutoff level divided patients with and without symptoms with 93.7% sensitivity and 91.6% specificity. The selection of 73.5% as the cutoff value for PTH decrease resulted in 91.6% sensitivity and 87.5% specificity. CONCLUSION: PTH1 levels and the drop in PTH levels are reliable predictors of developing symptomatic hypocalcemia after total thyroidectomy. PMID- 22666732 TI - Absence of mutations in PAX8, NKX2.5, and TSH receptor genes in patients with thyroid dysgenesis. AB - OBJECTIVES: To precisely classify the various forms of TD, and then to screen for mutations in transcription factor genes active in thyroid development. SUBJECTS AND METHODS: Patients underwent ultrasound, thyroid scan, and serum thyroglobulin measurement to accurately diagnose the form of TD. DNA was extracted from peripheral leukocytes. The PAX8, and NKX2.5 genes were evaluated in all patients, and TSH receptor (TSHR) gene in those with hypoplasia. RESULTS: In 27 nonconsanguineous patients with TD, 13 were diagnosed with ectopia, 11 with hypoplasia, and 3 with athyreosis. No mutations were detected in any of the genes studied. CONCLUSION: Sporadic cases of TD are likely to be caused by epigenetic factors, rather than mutations in thyroid transcription factors or genes involved in thyroid development. PMID- 22666733 TI - Lack of mutations in the leptin receptor gene in severely obese children. AB - OBJECTIVE: To analyze the LEPR gene in obese children and to investigate the associations between molecular findings and anthropometric and metabolic features. SUBJECTS AND METHODS: Thirty-two patients were evaluated regarding anthropometric characteristics, blood pressure, heart rate, serum glucose, insulin, leptin levels, and lipid profile. The molecular study consisted of the amplification and automatic sequencing of the coding region of LEPR in order to investigate new mutations. RESULTS: We identified a high prevalence of metabolic disorders: impaired fasting glucose in 12.5% of the patients, elevated HOMA-IR in 85.7%, low HDL-cholesterol levels in 46.9%, high triglyceride levels in 40.6%, and hypertension in 58.6% of the patients. The molecular study identified 6 already described allelic variants: rs1137100 (exon-2), rs1137101 (exon-4), rs1805134 (exon-7), rs8179183 (exon-12), rs1805096 (exon-18), and the deletion/insertion of the pentanucleotide CTTTA at 3'untranslated region. CONCLUSIONS: The frequency of alleles observed in this cohort is similar to that described in the literature, and was not correlated with any clinical feature. The molecular findings in the analysis of the LEPR did not seem to be implicated in the etiology of obesity in these patients. PMID- 22666734 TI - Mutation analysis in two Chinese families with multiple endocrine neoplasia type 1. AB - OBJECTIVE: This study aimed at identifing mutations in two Chinese genealogies with MEN1. SUBJECTS AND METHODS: Three members of two Chinese families with MEN1 were enrolled in this study, and all of the coding regions and adjacent sequences of the MEN1 gene were amplified and sequenced. RESULTS: A recurrent mutation of heterozygous change T>A at IVS 4+1 was found in family I, and a novel insGAGGTGG mutation (c.703-709dup7bp) resulted in a frameshift (p.A237Gfsx13) in family II. CONCLUSION: We are able to add a new mutation of MEN1 gene in Chinese patients with MEN1 that will be useful for the diagnosis and treatment of the disease. PMID- 22666735 TI - [Influence of thyroid function in CPK serum levels]. AB - OBJECTIVE: To determine serum CPK variation based on TSH e free T4 (FT4), and to assess serum CPK in pathological states of the thyroid (hyperthyroidism and hypothyroidism), in relation to the euthyroidism. MATERIAL AND METHODS: We evaluated retrospectively 6,230 laboratory results of TSH and CPK from 2007 to 2011. From these, 3,369 had free T4 results. We evaluated the correlation between CPK and TSH and the pathological states of the thyroid. RESULTS: The correlation between TSH and CPK was positive (r = 0.065), while that between CPK and FT4 was negative (r = -0.091, p < 0.05). From the total of results analyzed, 586 (9.4%) were measures of hyperthyroidism, with a median (range) of CPK of 98 U/L (27 to 1,113), and 556 (8.9%) were of hypothyroidism, with CPK of 114 U/L (25-4,182). CONCLUSION: A positive correlation was found between serum CPK and TSH, and a negative correlation between CPK and FT4. CPK was lower in the group with hyperthyroidism, and greater in that with hypothyroidism. PMID- 22666736 TI - [Secular trends in age at menarche in relation to body mass index]. AB - OBJECTIVE: To evaluate the secular trend of menarche according to body mass index (BMI). SUBJECTS AND METHODS: Six hundred and eighty five girls (7-18 years) assessed in 2001 were compared with 750 evaluated in 2010. They were grouped by BMI Z-score: (thin + normal) and (overweight + obese). Menarche was reported by status quo and age at menarche estimated by a logit model. We used the Qui-square test, Mann-Whitney test, and Logistic Regression, at a 5% significance level. RESULTS: Menarche advanced 3.24 months. There was an increase in obesity, and a decrease of the prevalence of normal girls. Menarche was anticipated by 1.44 month in the thin + normal group and by 5.76 months in the overweight + obese group. There was no interaction between the effects determined by the evaluated period and nutritional diagnosis. CONCLUSIONS: Although both the period and BMI influence the menarche, one cannot attribute this advance only to changes in the nutritional profile of the sample. Other factors that were not tested may also contribute to this finding. PMID- 22666737 TI - Clinical and laboratory features of children and adolescents with congenital hypothyroidism due to dyshormonogenesis in southern Brazil. AB - OBJECTIVE: To characterize the phenotype of patients with congenital hypothyroidism (CH) due to dyshormonogenesis, and to hypothesize on the degree of genetic defect. SUBJECTS AND METHODS: Patients with dyshormonogenesis were subdivided into G1 (radioactive iodine uptake, RAIU > 15%; n = 62) and G2 (RAIU < 15%; n = 32). Thyroglobulin (TG) was measured in all patients; perchlorate discharge test (PDT) was performed in G1; and saliva-to-plasma radioiodine ratio (I- S/P) in G2. RESULTS: Levels of TSH, TT4, and FT4 before treatment and upon diagnosis confirmation were significantly different in both groups, but not between groups. In G1, 27 patients developed goiter; 17 had positive PDT (14%-71% discharge), 11 had TG < 2.5 ng/dL (one with high TSH), and one developed thyroid carcinoma. In G2, four patients developed goiter, and three had low I- S/P. CONCLUSION: These data suggest an iodide organification defect in 17 cases; an iodide transport defect (NIS defect) in three, probable TSH resistance in 10, and a TG synthesis defect in two cases. PMID- 22666738 TI - Two cases of thyroid sarcoidosis presentation as painful, recurrent goiter in patients with Graves' disease. AB - Sarcoidosis rarely involves the thyroid gland. Pain in the thyroid gland area was only sporadically reported in patients suffering from this disease. The aim of this paper is to report and discuss the cases of two female patients with Graves' disease who presented painful, rapidly growing, recurrent goiters (after strumectomy in their early adult lives). Invasive treatment was applied and sarcoidosis was revealed histologically. The first patient suffered from dysphagia and dyspnoea due to large goiter; skin lesions were present as well. Sarcoidosis was diagnosed in histological examination of the thyroid tissue specimens. Steroid treatment was ineffective; thus, the thyroid was removed. Two years later thyroid sarcoidosis recurred as a painful goiter and surgical treatment was applied once again. In the second case, thyroid ultrasound findings suggesting malignancy, and prompted the decision to perform thyroidectomy despite the fact that FNAB (fine needle aspiration biopsy) revealed cells indicative of a "granulomatous disease in the post-resection scar" and results of the thorax high resolution computed tomography scan suggested pulmonary sarcoidosis. Pathological examination confirmed sarcoidosis. However, a papillary cancer focus was also found. PMID- 22666739 TI - Anatomical study of the positioning of guide wires for the reconstruction of the two bands of the anterior cruciate ligament using transtibial technique. AB - PURPOSE: To determine whether it is possible and the difficulty of anatomical placement of guide wires for reconstruction of the two bands of the anterior cruciate ligament using transtibial technique and to measure the angle and positioning of the anatomic tibial guide wires for this technique. METHODS: Ten cadaver knees were dissected and a guide wire was positioned in the center of origin and insertion of each band. Were collected measurements of the distance from: 1) the entry point of the guide wire on tibial tuberosity; 2) the medial end of the tibia; 3) the tibial articular surface. Were also measured the medial and caudal angles of the guide wires. RESULTS: For the anteromedial band the medial angle was 19 +/- 5o and the caudal was 44 +/- 4o.The distances were 20 +/- 2 mm from anterior tuberosity, 26 +/- 5 mm from the tibial plateau and 25 +/- 5 mm from the medial end of the tibia. For the posterolateral band the medial angle was 26 +/- 5o and the caudal one was 36 +/- 8 degrees . The distances were 31 +/- 6 mm for the anterior tuberosity, 24 +/- 4 mm for the tibial plateau and 17 +/- 7 mm from the end of the tibia. CONCLUSIONS: It is possible to position the guide wires of the two bands to reconstruct the anterior cruciate ligament using transtibial technique. The parameters for the proper positioning of the guide wire from anteromedial band is caudal angle of 44o with entry point 20 mm from anterior tuberosity; for the posterolateral band the caudal angle is 36o; from the tibial tuberosity the distance is 31 mm. This technique is difficult to perform leaving its questionable reproducibility. PMID- 22666740 TI - Fat embolism in liposuction and intramuscular grafts in rabbits. AB - PURPOSE: To evaluate the effects of fat embolism in organs such as lung and liver. METHODS: Twenty rabbits underwent autologous intramuscular fat grafting in the right thigh after liposuction. The groups were determined according to the postoperative day that occurred in euthanasia: 60, 90 and 120 day. Then, lung and liver were excised and sent to the histopathology laboratory for analysis in search of late injury secondary to a prior event of fat embolism in the tissues. RESULTS: The results showed a change in the macroscopic sample with discoloration of the liver tissue heterogeneously. There were no changes consistent with embolic effect under the microscope. CONCLUSION: The option of performing a technique of fat grafting with a less traumatic surgical procedure can be considered protective against embolic events, with no impact to late embolic events on the tissues. PMID- 22666741 TI - Radiolabeling of methanol extracts of yarrow (Achillea millefolium l) in rats. AB - PURPOSE: Current study is focused on extraction with methanol, purification, labeling with (131)I using iodogen method of the yarrow plant and investigating in vivo biological activity using biodistribution and imaging studies on healthy animal models. The aim of the study is to contribute plant extracts to discover new drugs in the diagnosis and treatment of several diseases. METHODS: Nine female and nine male healthy Wistar albino rats, which were approximately 100-150 g in weight, were used for biodistribution studies. For imaging studies four healthy male Balb-C mice were used. Quality control studies were done utilizing thin layer radio chromatography (TLRC) and high performance liquid chromatography (HPLC) methods. For biodistribution studies, (131)I radiolabeled Peak 7 ((131)I Peak 7) was sterilized and injected into the tail veil of rats and imaging studies were obtained using Kodak FX PRO in vivo Imaging System. RESULTS: The radiolabeling yield of each purified the bioactive extracts of the yarrow plant, seven peaks was between 79 and 92%. The highest radiolabeling yield was calculated for (131)I radiolabeled seventh peak ((131)I-Peak 7) (92.78 +/- 5.04, n=5). For this reason the biodistribution and imaging studies were done for (131)I-Peak 7. That's why; these studies with Peak 7 were carried out. CONCLUSION: Peak 7 was radiolabeled with (131)I in high yield for using imaging and therapeutic studies in nuclear medical applications. PMID- 22666742 TI - Synergistic suppression of pre-perfusion of donor livers with recipient serum and cobra venom factor treatment on hyperacute rejection following liver xenotransplantation. AB - PURPOSE: To investigate synergistic suppression of donor liver pre-perfusion with recipient serum (RS) and cobra venom factor (CVF) treatment on hyperacute rejection (HAR) following liver xenotransplantation. METHODS: Guinea-pigs (GP, n=24) and Sprague-Dawley rats (SD, n=24) were recruited. Before transplantation, serum was collected from SD rats and used for preparation of inactivated complements. GP and SD rats were randomly assigned into four groups (n=6), respectively: RS group, CVF group, RS+CVF group and control group. Orthotopic liver xenotransplantation was performed with modified two-cuff technique. The survival time and liver function of recipients, morphological and pathological changes in rat livers were investigated. RESULTS: There was no piebald like change in the recipient livers in all experiment groups. The survival time of recipients in all experiment groups was longer than that in control group (p<0.05). Moreover, the survival time in the RS+CVF group was markedly longer than that in the RS group (p<0.01) and CVF group (p<0.05). The serum ALT level in all experiment groups were lower than that in the control group (p<0.05). Furthermore, the ALT level in the RS+CVF group was significantly lower than that in the CVF group (p<0.05) and RS group (p<0.01). The histological damages were significantly improved when compared with the control group, and the histological damages in the RS+CVF group were milder than those in the remaining groups (p<0.05) CONCLUSION: Pre-perfusion of donor liver with recipient serum and cobra venom factor treatment can exert synergistic suppressive effects on the hyperacute rejection following liver xenotransplantation. PMID- 22666743 TI - Non heart beating organ donor: new experimental model in pigs. AB - PURPOSE: To describe technical aspects of a new experimental model that simulates a non heart beating organ donor. METHODS: Landrace pigs were operated on and cardiac arrest was obtained by means of myocardial infarction and interruption of ventilator support. RESULTS: Mean cardiac frequency, systolic and diastolic blood pressure levels, central venous pressure, oxygen saturation and concentration of expired CO(2) dropout occurred at seven minutes after cardiac arrest. CONCLUSION: The procedure was easily reproduced and a homogeneous circulatory failure could de obtained by the end of seven minutes. The model is suitable for further studies regarding abdominal organ transplantation. PMID- 22666744 TI - Oncoplastic approach in the conservative treatment of breast cancer: analysis of costs. AB - PURPOSE: To analyze the direct costs of conservative surgical treatment of breast cancer, performed in a university hospital, to the Brazilian National Health Care Public System (SUS), checking the impact of the oncoplastic approach on these costs. METHODS: One hundred thirty eight breast cancer patients who had undergone conservative treatment with oncoplastic approach (n=36) or not (control group, n=102), in the period from 2005 to 2010, were enrolled. Sociodemographic and clinical data were recorded. The direct costs of the surgical procedure were obtained and analyzed. RESULTS: Groups did not differ in regard to age (p=0.963), and patients in oncoplastic group had a longer time of hospital stay (p=0.000). The median direct cost for the oncoplastic group was R$461.00 and for the control group was R$229.00 (p=0.000). CONCLUSION: The oncoplastic approach has generated higher direct costs in conservative surgical treatment of breast cancer to SUS. PMID- 22666745 TI - Ki-67 expression score correlates to survival rate in gastrointestinal stromal tumors (GIST). AB - PURPOSE: To evaluate the immunohistochemical expression of p16, Ki-67, p53 and Bcl-2 proteins in gastrointestinal stromal tumors (GIST); to assess the possible association between these variables and clinical and histopathological factors of cancer; and to check for prognostic value of these variables (survival and recurrence). METHODS: A sample of 55 patients treated surgically for GIST in three hospitals was studied. The surgically excised tumors were confirmed as GIST by KIT, vimentin, desmin S100 protein, CD117, 1A4 and CD34 assessment in paraffin blocks. RESULTS: Only 9 (16%) cases of GIST were positive for p53, p16 was positive among 43.6%; 80% of GISTs showed staining for Bcl-2. The proliferative index (expressed as the proportion of positive cells) assessed by immunohistochemical expression of Ki-67 was high in 49% of cases. Elevated Ki-67 scores were associated to high histological grade (p=0.0026) and mitosis index, MI (p=0.0001). High Ki-67 index was associated to death. Expression of p53, p16 and Bcl-2 did not correlate to morphological or clinical variables. CONCLUSIONS: Ki-67 immunohistochemical evaluation should be included in preoperative evaluation of GIST biopsies or surgical specimens as a prognostic tool for clinical staging; and all other proteins studied (Bcl-2, p53 and p16) did not play a role in GIST metabolic or carcinogenic process, remaining without prognostic value. PMID- 22666746 TI - Application of high frequency bipolar electrocoagulation LigaSureTM in appendix vermiformis of rabbits with or without acute inflammatory process. AB - PURPOSE: To evaluate the efficacy of the use of LigaSureTM in appendectomy, with or without acute inflammatory process, and to compare with simple ligature and conventional therapy. METHODS: A total of 30 rabbits (Oryctolagus cuniculus) randomly allocated in two groups, group A and B, of 15 animals each were used. The group A without acute appendicitis and the group B with acute appendicitis were submitted to appendectomy. After, the groups were subdivided into three groups, each group containing five rabbits submitted to simple ligature, conventional therapy and application of LigaSureTM. We assessed macroscopic and microscopy parameters of appendiceal stump and operative wound. RESULTS: The group with acute appendicitis that LigaSureTM was applied had fibrosis in 100% of animals, as well as in the other operative techniques used. It suggested that application of LigaSureTM is efficient as other techniques used in healing of appendiceal stump. CONCLUSIONS: The application of LigaSureTM induces the formation of fibrosis in the appendiceal stump. The technique proved efficacy to induce enough fibrous tissue to obstruct leakage of enteric content. PMID- 22666747 TI - Effective reinnervation of the quadriceps femoris by spinal ventral root cross anastomosis in rats. AB - PURPOSE: To study the effective recovery of the quadriceps femoris by spinal ventral root cross-anastomosis in rats. METHODS: End-to-end anastomosis was performed between the left L(1) and L(3) ventral roots using autogenous nerve graft, and the right L(1) and L(3) roots were left intact. In control animals, the left L(3) ventral root was cut and shortened, and anastomosis was not performed. Six months postoperatively, the movement of low extremities was detected by electrophysiological examination, hindlimb locomotion and basso, beattie and bresnahan (BBB) scoring at one, three, seven, 14, 21 and 28 days after SCI. Fluorescence retrograde tracing with TRUE BLUE (TB) and HE staining were performed to observe the nerve regeneration. RESULTS: Six months after surgery, the anastomotic nerve was smooth and not atrophic. The amplitudes of action potential were 7.63 +/- 1.86 mV and 6.0 +/- 1.92 mV respectively before and after the spinal cord hemisection. The contraction of left quadriceps femoris was induced by a single stimulation of the anastomotic nerve. The locomotion of left hindlimb was partially restored after spinal cord hemisection while creeping and climbing. In addition, there was significant difference in the BBB score at one, three and seven days after SCI. TB retrograde tracing and neurophysiologic observation indicated efficient reinnervation of the quadriceps femoris. CONCLUSION: The cross-anastomosis between spinal ventral root can partially reconstruct the function of quadriceps femoris following SCI and may have clinical implication for the treatment of human SCI. PMID- 22666748 TI - Treatment of unstable sacral fractures with percutaneous reconstruction plate internal fixation. AB - PURPOSE: To study the effects of percutaneous reconstruction plate internal fixation in the treatment of unstable sacral fractures. METHODS: Percutaneous reconstruction plate internal fixation was applied on 21 cases of unstable sacral fracture (15 males and six females, at age range of 16-65 years, mean 38.3 years) including four cases of Denis Zone I, 14 cases of Zone II and three cases of Zone III. In operation, an arc incision (about 3-5 cm long) was made along the iliac crest on the outside border of posterior superior iliac spine (PSIS) on both sides, and then the plate was transported from the wounded side to the opposite one through the subcutaneous tunnel. RESULTS: The mean incision length, operation time, intraoperative blood loss was 4.3 cm, 45.2 min, and 160.8 ml respectively. All these patients were followed up for 12-33 months (average 16.3 months), which showed no incision infection, intraoperative neurovascular injury, internal fixation loose or breakage, disunion, or obvious lower limb length inequality. The function result was rated as excellent in six cases, good in 12 and fair in 3, with excellence rate of 85.7%, according to the Majeed scoring system. CONCLUSION: Percutaneous reconstruction plate internal fixation is an ideal surgical approach to unstable sacral fractures, as it is easy, safe, causing less trauma and fewer complications, and conducive to quicker recovery. PMID- 22666749 TI - Cervical esophagogastric anastomosis with invagination after esophagectomy. AB - PURPOSE: To evaluate the incidence of fistula and stenosis of the cervical esophagogastric anastomosis with invagination of the proximal esophageal stump into the stomach after subtotal esophagectomy. METHODS: We studied 54 patients who underwent subtotal esophagectomy, 45 (83.3%) patients with carcinoma and nine (16.6%) with advanced megaesophagus. In all cases the cervical esophagogastric anastomosis was performed with the invagination of the proximal esophageal stump inside the stomach. RESULTS: Three (5.5%) patients had a fistula at the esophagogastric anastomosis, two of whom with minimal leakage of air or saliva and with mild clinical repercussion; the third had a low output fistula that drained into the pleural space, and this patient developed empyema that showed good progress with drainage. Fibrotic stenosis of anastomosis occurred in thirteen (24%) subjects and was treated successfully with endoscopic dilatation. CONCLUSION: Cervical esophagogastric anastomosis with invagination of the proximal esophageal stump into the stomach tube presented a low rate of esophagogastric fistula and stenosis, thus becoming an attractive option for the reconstruction of alimentary transit after subtotal esophagectomy. PMID- 22666750 TI - Evaluation of the key words used in articles of the Acta Cirurgica Brasileira from 1997 to 2012. AB - PURPOSE: To evaluate the key words used in Acta Cirurgica Brasileira from 1997 to 2012. METHODS: All the key words of all articles published in regular issues between 1997 and 2012 were analyzed, ensuring that these key words were in the MeSH database (Medical Subjects Headings) and the most used subject headings and most wrong repeated key words were ranked. RESULTS: > 4230 key words used in 990 articles were analyzed. Only 579 key words (13.68%) were not in the MeSH database, considering that there was a statistically significant decrease over the years (p<0.001). The three most used key words were Rats, Dogs and Wound healing. Among the wrong ones, the key words were Adhesions, Experimental surgery and Anatomosis. CONCLUSION: There was a gradual improvement in the amount of key words used that belonged to the MeSH database, and there were 618 articles (62.42%) with all key words correct. PMID- 22666751 TI - A novel model of distal colon cancer in athymic mice. AB - PURPOSE: The present a novel adenocarcinoma model in athymic mice. METHODS: Seven athymic mice were used. Colon diversion and distal fistula were made. Adenocarcinoma cells were inoculated in the submucosa of fistula. Tumor growth was monitored daily. Scintigraphy with 99mTc-MIBI was performed to identify the tumor. RESULTS: The model of distal colon cancer is feasible. Tumor detection was possible by both, macroscopically and molecular imaging. All resections demonstrated poorly differentiated tumors. Colon obstruction occurred in one case, similarly to evolution in human tumors of distal colon. CONCLUSION: The proposed model of distal colon cancer is feasible, allows for easy monitoring of tumoral growth by both, macroscopically and molecular imaging, and is suitable for studying the evolution of tumor with implementation of cytotoxic therapy in vivo. PMID- 22666752 TI - The jejunoileal bypass provokes morphological changes in the large intestine? An experimental study in rats. AB - PURPOSE: To analyse histopathological alterations characterized by the mitotic index in the mucosa of the large intestine in Wistar rats submitted to jejunoileal bypass operation after continued administration of sodium nitrite and vitamin C to different groups. METHODS: Eighty male Wistar rats were employed and separated into 12 groups. In the control group (20 rats): five animals ingested only water; five animals received vitamin C; five animals received sodium nitrite and five received sodium nitrite + vitamin C. In the sham group (20 rats), the animals were anesthetized and underwent midline laparotomy and only intestinal manipulation was performed: five animals ingested only water; five animals received vitamin C; five animals received sodium nitrite and five received sodium nitrite + vitamin C. In the operated group 40 rats underwent a jejunoileal bypass surgery: ten animals ingested only water; ten animals received vitamin C; ten animals received sodium nitrite and ten received sodium nitrite + vitamin C. The mean weight of the animals was measured weekly. The large intestine was subdivided into cecum (S1), ascending colon (S(2)), transverse colon (S(3)), descending colon (S(4)) and rectum (S(5)) for histopathological analysis and mitotic counts. The statistical analysis was used to compare the mitotic indices. The level of significance was 5%. RESULTS: The mean of all the segments indicates that the sodium nitrite+vitamin C group obtained the lowest mitotic index compared to the other treatments in the control group. The segments S(1) and S(2) showed a statistical difference with the vitamin C treatment: a higher mitotic index and better preservation of the mucosa in the operated group. In the sham group the main statistical difference occurred only in the sodium nitrite+vitamin C group between the means of the segments. CONCLUSIONS: The comparison of all the colonic segments of the various groups revealed a lower mitotic index in the animals treated with sodium nitrite+vitamin C. In addition, it was found that vitamin C did not present a statistically significant inhibiting effect on the preservation of the mucosa and the mitotic index. PMID- 22666753 TI - Effects of bromopride on the healing of left colonic anastomoses in rats with induced abdominal sepsis. AB - PURPOSE: To evaluate the effects of bromopride on the healing of left colonic anastomoses in rats with induced abdominal sepsis. METHODS: Forty rats were divided into two groups to receive either bromopride (experimental group- E) or saline (control group- C). Each group was divided into subgroups of ten animals each to be euthanized on third (E3 and C3) or seventh day (E7 and C7) after surgery. Sepsis was induced by cecal ligation and puncture. The rats underwent segmental left colon resection and end-to-end anastomosis. Adhesion formation, tensile strength and hydroxyproline concentration were assessed. Histomorphometry of collagen and histopathological analysis were also performed. RESULTS: On postoperative third day, anastomoses in bromopride-treated animals showed lower tensile strength (p=0.02) and greater reduction in hydroxyproline concentration (p=0.04) than in control animals. There was no statistical difference in these parameters on seventh day, and the remaining parameters were similar across subgroups. Collagen content was also similar across subgroups. CONCLUSION: In the presence of abdominal sepsis, the administration of bromopride was associated with decreased tensile strength and hydroxyproline concentration in left colonic anastomoses in rats three days after surgery. PMID- 22666754 TI - Evaluation of the damage caused by clamping or section of cervical sympathetic nerve in rabbits. AB - PURPOSE: To study the macro and microscopic evaluation of the damage caused by clamping or section of cervical sympathetic nerve in rabbits, quantifying the collagen in the lesions. METHODS: Twenty rabbits were divided into two groups of ten, doing in group 1 (section) section of the right cervical sympathetic nerve, while in group 2 (clipping) clipping of the nerve. All rabbits were induced to death on the seventh day after surgery. The macroscopic variables were: consequences of nerve lesion, clip appearance, presence of infection and adhesions around the nerve. Microscopy used hematoxylin-eosin staining to evaluate the stages and the degree of inflammation and necrosis, and F3BA Picrosirius red staining to quantify collagen. Mann-Whitney test was used for comparisons of collagen types I and III between groups. Fisher exact test analyzed the macroscopic variables, the degree of inflammation and necrosis. RESULTS: There was no discontinuity of nerve injury in the clipping group, as well as the clip was closed in all animals. The presence of severe adhesions was significantly higher in the clipping group (p<0.05). There was no significant difference on other variables macroscopically analyzed. There was no significant difference between groups regarding the type of inflammatory process and its intensity, as well as the presence of necrosis and collagen deposition in the nerves. CONCLUSIONS: In the macroscopic evaluation, the section caused discontinuity, which did not occur in the clamping group; there was no development of local infection; the clipping of the cervical sympathetic nerve was linked to the presence of a greater number of adhesions in comparison to the section group. Microscopically, no difference existed in relation to the type and intensity of inflammation reaction between the groups; occurred predominance of chronic and severe inflammation on the specimens; the necrosis was noticed equally in both groups; there was predominance of type I collagen deposition in relation to type III in both groups. PMID- 22666755 TI - Combination hyperbaric oxygen and temozolomide therapy in C6 rat glioma model. AB - PURPOSE: Temozolomide (TMZ) has anti-tumor activity in patients with malignant glioma. Hyperbaric oxygen (HBO) may enhance the efficacy of certain therapies that are limited because of the hypoxic tumor microenvironment. We examined the combined effects of TMZ-HBO in a rat glioma model. METHODS: After stereotactic injection of C6/LacZ rat glioma cells into the Wistar rats brain, the rats were randomly assigned to three treatment groups [group 1, control treatment; group 2, TMZ alone; group 3, a combination of TMZ and HBO]. Rats were sacrificed 18 days after treatment, and number of intra-/peri-tumoral vessels, microendothelial proliferations, immunohistochemistry and necrotic area were evaluated. RESULTS: Tumoral tissue was stained only sparsely with GFAP. Temozolomide treatment was significantly decreased in tumor tissue intratumoral vessel number / total tumor area level. The level of Ki67 was significantly decreased in the tumor tissue of the group 3. Additionally, the total necrotic area / total tumor volume (%) was decreased significantly in tumor tissue of the group 3 rats compared to group 1 and 2. CONCLUSION: The combination of hyperbaric oxygen with temozolomide produced an important reduction in glioma growth and effective approach to the treatment of glioblastoma. PMID- 22666756 TI - Long-term effects of the testicular torsion on the spermatogenesis of the contralateral testis and the preventive value of the twisted testis orchiepididymectomy. AB - PURPOSE: To determine whether the testicular torsion causes long-term effects on the spermatogenesis of the contralateral testis, and whether the orchiepididymectomy of the twisted testis could prevent them, using specific spermatogenesis parameters to elucidate the conflicting results in the literature. METHODS: Seventy-four pubertal male Wistar rats were randomly selected. The experimental group consisted of 40 rats, divided into four subgroups, submitted to 1.080 degrees counterclockwise left testicular torsion and its scrotal fixation at the beginning of the experiment, and left orchiepididymectomy at one, five, ten and 90 days, respectively. The control group consisted of 24 rats, divided into four sham operation control subgroups. An additional control subgroup consisted of the ten remaining rats, submitted only to the left orchiepididymectomy at the beginning. At 90 days, the contralateral testes of the experimental and control subgroups were collected for the evaluation of their spermatogenesis parameters: testicular weight, seminiferous tubular diameter, Johnsen score and differential counting of the germ cells. RESULTS: No statistically significant differences were observed among the experimental and control subgroups for all of the spermatogenesis parameters of the contralateral testes. CONCLUSIONS: Testicular torsion does not cause long term effects on the spermatogenesis of the contralateral testis in pubertal rats, and the orchiepididymectomy of the twisted testis is not necessary for preventive purposes for the contralateral spermatogenesis. PMID- 22666757 TI - Non-cancerous prognostic factors of hepatocellular carcinoma after liver transplantation. AB - PURPOSE: To explore non-cancerous factors that may be related with medium-term survival (24 months) after liver transplantation (LT) in this data from northeast Brazil. METHODS: A cross-sectional study was carried out in patients who underwent deceased-donor orthotopic LT because hepatocellular carcinoma (HCC) at the University of Pernambuco, Brazil. Non-cancerous factors (i.e.: donor-, receptor-, surgery- and center-related variables) were explored as prognostic factors of medium-term survival using univariate and multivariate approachs. RESULTS: Sixty-one patients were included for analysis. Their three, six, 12 and 24-month overall cumulative survivals were 88.5%, 80.3%, 73.8% and 65.6%, respectively. Our univariate analysis identified red blood cell transfusion (Exp[b]=1.26; p<0.01) and hepato-venous reconstruction technique (84.6% vs. 51.4%, p<0.01; respectively for piggyback and conventional approaches) as significantly related to post-LT survival. The multivariate analysis confirmed the hepato-venous reconstruction technique was an independent prognostic factor. CONCLUSION: The piggyback technique was related to improved medium-term survival of hepatocellular carcinoma patients after liver transplantation in this northeast Brazilian sample. PMID- 22666758 TI - Effects of dorsal root ganglion destruction by adriamycin in patients with postherpetic neuralgia. AB - PURPOSE: To investigate the effects of dorsal root ganglion destruction in patients with postherpetic neuralgia (PHN). METHODS: Seventy-two patients with PHN selected were randomly divided into two groups (n=36). Group A was the control group (treated by injection) and group B was the group of dorsal root ganglion destruction by adriamycin. Visual analog scale scores (VAS), SAS, SF-MPQ scores. Clinical effects and therapy safety were evaluated before therapy, one week, three and six months after therapy. Forty-four patients were available for intention-to-treat analysis. RESULTS: The average pain scores on the Likert scale were significantly reduced at each point in group B. Patients in group B reported clinical effectiveness at six months as excellent response, good response, improved but unsatisfactory or unchanged 16, 12 and 8.VAS scores at each time point after the operation were lower than that before operation and in group A, there was significant difference. Patients showed significant improvement in sleep scores in group B. There was significant difference at T2 in group A than T1. There was no significant difference in group A at T3, T4 after the operation than that before operation. Between group comparison: there was significant difference between group A and group B at each time point after the operation. CONCLUSIONS: Dorsal root ganglion destruction by adriamycin under guidance of C arm perspective, the puncture operation was accurate without any adverse reaction or serious complications, which could effectively relieve pain of patients with postherpetic neuralgia, but the long-term effects needed further study. PMID- 22666759 TI - Levels of CEA and Ca 19 - 9 in the sera and peritoneal cavity in patients with gastric and pancreatic cancers. AB - PURPOSE: Tumor markers are substances found in blood and other biological fluids if tumor is present in the body. They can be produced by tumor itself or can be results of cancer - body relation. They may be used in the follow-up of cancer patients to identify tumor recurrence. Pre-treatment levels have prognostic tool and could signalize persistence of minimal residual disease despite radical surgery. METHODS: We operated on 52 patients with upper GI malignancy (32 with gastric cancer and 20 with pancreatic cancer). Blood samples were taken before surgery and peritoneal samples immediately after laparotomy before any manipulation with tumor. All samples were examined by standard biochemical technique and the level was compared with a stage of the disease. RESULTS: Patients suffering from gastric carcinoma of stage I and II had higher level of both markers in sera then in the peritoneal cavity, however most of them were within physiological range. Patients in stage III and IV had average marker levels in the peritoneal cavity higher than in sera. Number of positive findings was increasing according to the stage of the disease. The peritoneal levels of both markers varied extremely in higher stages. In patients suffering from pancreatic carcinoma the CEA levels both in sera and peritoneal cavity were parallel but peritoneal levels were slightly higher in stages III and IV. Ca 19 - 9 was more sensitive for pancreatic cancer. The percentage of positive findings was higher in sera but the level of Ca 19 - 9 was higher in the peritoneal cavity. The number of positive findings again correlated with the stage of the disease. CONCLUSIONS: Levels of tumor markers in sera could signalize inoperability of tumor (Ca 19 - 9 in cases of pancreatic carcinoma); peritoneal levels could predict R1 resection especially in gastric cancer patients and risk of early peritoneal recurrence of the disease. Difference between the levels in the peritoneum and sera may signalize the route of dissemination (hematogenous and intraperitoneal). PMID- 22666760 TI - Rat an experimental model for burns: a systematic review. AB - PURPOSE: To revise and systematize scientific knowledge of the experimental model for cutaneous burns in rats. METHODS: A bibliographical review from 2008 up to January 2011 in PubMed, EMBASE and LILACS was undertaken. Were used the keywords: animal models, burns and rats. 221 studies were identified, and 116 were selected. RESULTS: It was found that: 54/86 (62.7%) had third degree burns; 55/73 (75.3%) studied the back; 45/78 (57.6%) used heated water and 27/78 (35.9%) incandescent instruments; 39/78 (50%) studied systemic effects; 22/71 (31%) used ketamine associated with xylazine; 61/64 (95.3%) performed depilation with appropriate equipment; 36/72 (50%) used microscopy; more than 50% did not describe analgesia or antibiotics during the postoperative period; in 42/116 (36.2%) postoperative fluid therapy was performed; and the time interval after the burn, up to the beginning of the results analysis varied from 7s up to four weeks. Legislation issues on burn experiments are discussed. CONCLUSION: The hot water was the main method to induce burns those of third degree on the back, with anesthesia using ketamine and xylazine, after depilation. These were evaluated microscopically, without using analgesia or an antibiotic during the postoperative period. The studies were not very reproducible. PMID- 22666761 TI - Biomechanical analysis of titanium plate systems in mandibular condyle fractures: a systematized literature review. AB - PURPOSE: To conduct a systematized review of the literature about the main methodologies used to evaluate the biomechanical fixation systems with titanium plates in fractures of the mandibular condyle. METHODS: A systematized review of literature was performed in the electronic databases PubMed, EMBASE, LILACS and MEDLINE without restriction of the publication date. The eligibility criteria were laboratory studies involving mandibular condyle fractures, studies using titanium plates, biomechanical studies, in vitro and computational studies involving the finite element method (FEM). RESULTS: Eleven articles that met the eligibility criteria were selected, including seven articles involving in vitro studies and four studies with biomechanical analysis by using FEM. CONCLUSION: Although few articles have used the finite element method, the results of in vitro studies were similar to those found in computational studies, regarding to the stable use of two titanium miniplates. PMID- 22666762 TI - May titanium spiral tacks contribute to intra-abdominal adhesion formation? AB - PURPOSE: To verify if titanium spiral tacks may contribute to intra-abdominal adhesion formation in rabbits. METHODS: Ten New Zealand white rabbits were used. Through videolaparoscopic surgery two titanium spiral tacks (ProTack((r)), Covidien((r))) were applied in the right flank. After 30 days the animals were submitted to evaluate peritoneal cavity by videolaparoscopy. RESULTS: No adhesion was found where the titanium spiral tacks were placed. CONCLUSION: Titanium spiral tacks for fixation do not cause adhesions in rabbits. PMID- 22666763 TI - Comparison between the traditional and the new training model using rabbits in the assessment. AB - PURPOSE: Compare the new training model for vessel ligation with the traditional using rabbits in the assessment. METHODS: From 106 academics of the Division of Operative Technique and Experimental Surgery, 36 were divided into two groups and offered them two training models of ligature. The group was invited to participate to an experimental procedure with rabbits and reproduce the technique trained. The procedure consisted of performing ligatures in saphenous veins of the legs of rabbits. The students were evaluated by objective criteria by an observer evaluator and answered a questionnaire at the end of the procedure. RESULTS: The medical students who have had training with the new model had a higher number of hits compared to the other group performing ligatures without clamping with hemostatic forceps (p<0.05). There was also a higher number of hits for the new model group to perform ligation temporary and permanent ligation with the use of forceps (p>0.05). The questionnaires indicated that the new model develops more ability to work in groups (p=0.088). CONCLUSIONS: The project promotes the implementation of the new model for training ligature, indicating that the new model is better to the traditional surgical practice. PMID- 22666764 TI - Cell proliferation and apoptosis in ameloblastomas and keratocystic odontogenic tumors. AB - A high proliferative activity of the odontogenic epithelium in ameloblastoma (AM) and keratocystic odontogenic tumor (KOT) has been demonstrated. However, no previous study has simultaneously evaluated cell proliferation and apoptotic indexes in AM and KOT, comparing both lesions. The aim of this study was to assess and compare cell proliferation and apoptotic rates between these two tumors. Specimens of 11 solid AM and 11 sporadic KOT were evaluated. The proliferation index (PI) was assessed by immunohistochemical detection of Ki-67 and the apoptotic index (AI) by methyl green-pyronine and in situ DNA nick end labelling methods. KOT presented a higher PI than AM (p<0.05). No statistically significant difference was found in the AI between AM and KOT. PI and AI were higher in the peripheral cells of AM and respectively in the suprabasal and superficial layers of KOT. In conclusion, KOT showed a higher cell proliferation than AM and the AI was similar between these tumors. These findings reinforce the classification of KOT as an odontogenic tumor and should contribute to its aggressive clinical behavior. PMID- 22666765 TI - 1-Year clinical study of indirect resin composite restorations luted with a self adhesive resin cement: effect of enamel etching. AB - In vitro studies have recommended enamel-etching before luting indirect restorations with self-adhesive resin cement. However, there is no scientific proof that this procedure has any clinical relevance. Thus, the aim of this study was to evaluate the effect of enamel-etching on the marginal quality of indirect composite resin restorations (inlay/onlay) using the self-adhesive cement RelyX Unicem clicker. Forty-two posterior teeth were selected from 25 patients that presented one or two teeth with large restorations in need of replacement. All teeth were prepared by the same operator and impressed with polyvinylsiloxane material. The composite resin restorations were built over plaster casts using the incremental technique with a LED device for light-curing the increments. The inlays/onlays were cemented according to one of the following protocols: 1. Etched group (ETR) - selective enamel phosphoric-acid etching + RelyX Unicem clicker; 2. Non-etched group (NER) - RelyX Unicem clicker alone. Each surface was light-cured for 60 s. Recalls occurred after 1 week (baseline), 6 and 12 months when the teeth were evaluated according to previously established scores (modified USPHS criteria). The clinical analysis showed little or no visible changes in the marginal quality after 1 year, even though a probe could detect all the restorations margins. Statistical analysis (Fisher's exact test, p<0.05) detected no differences between the groups after 12 months. No restorations failed and no secondary caries were found. Enamel acid etching had no clinical relevance on the marginal quality of indirect composite resin restorations luted with RelyX Unicem clicker after 1 year of follow up. PMID- 22666766 TI - Effect of Nd:YAG laser combined with fluoride on the prevention of primary tooth enamel demineralization. AB - Most studies dealing with the caries preventive action of Nd:YAG laser have been done in permanent teeth and studies on primary teeth are still lacking. The aim of this study was to evaluate in vitro the effect of Nd:YAG laser combined or not with fluoride sources on the acid resistance of primary tooth enamel after artificial caries induction by assessing longitudinal microhardness and demineralization depth. Sixty enamel blocks obtained from the buccal/lingual surface of exfoliated human primary molars were coated with nail polish/wax, leaving only a 9 mm2 area exposed on the outer enamel surface, and randomly assigned to 6 groups (n=10) according to the type of treatment: C-control (no treatment); APF: 1.23% acidulated phosphate fluoride gel; FV: 5% fluoride varnish; L: Nd:YAG laser 0.5 W/10 Hz in contact mode; APFL: fluoride gel + laser; FVL: fluoride varnish + laser. After treatment, the specimens were subjected to a des-remineralization cycle for induction of artificial caries lesions. Longitudinal microhardness data (%LMC) were analyzed by the Kruskal-Wallis test and demineralization depth data were analyzed by oneway ANOVA and Fisher's LSD test (a=0.05). APFL and APF groups presented the lowest percentage of microhardness change (p<0.05). Demineralization depth was smaller in all treated groups compared with the untreated control. In conclusion, Nd:YAG laser combined or not with fluoride gel/varnish was not more effective than fluoride alone to prevent enamel demineralization within the experimental period. PMID- 22666767 TI - Effect of bleaching on sound enamel and with early artificial caries lesions using confocal laser microscopy. AB - The aim of this study was to evaluate effect of bleaching agents on sound enamel (SE) and enamel with early artificial caries lesions (CL) using confocal laser scanning microscopy (CLSM). Eighty blocks (4 x 5 x 5 mm) of bovine enamel were used and half of them were submitted to a pH cycling model to induce CL. Eight experimental groups were obtained from the treatments and mineralization level of the enamel (SE or CL) (n=10). SE groups: G1 - unbleached (control); G2 - 4% hydrogen peroxide (4 HP); G3 - 4 HP containing 0.05% Ca (Ca); G4 - 7.5% hydrogen peroxide (7.5 HP) containing amorphous calcium phosphate (ACP). CL groups: G5 - unbleached; G6 - 4 HP; G7 - 4 HP containing Ca; G8 - 7.5 HP ACP. G2, G3, G6, G7 were treated with the bleaching agents for 8 h/day during 14 days, while G4 and G8 were exposed to the bleaching agents for 30 min twice a day during 14 days. The enamel blocks were stained with 0.1 mM rhodamine B solution and the demineralization was quantified using fluorescence intensity detected by CLSM. Data were analyzed using ANOVA and Fisher's tests (alpha=0.05). For the SE groups, the bleaching treatments increased significantly the demineralization area when compared with the unbleached group. In the CL groups, no statistically significant difference was observed (p>0.05).The addition of ACP or Ca in the composition of the whitening products did not overcome the effects caused by bleaching treatments on SE and neither was able to promote remineralization of CL. PMID- 22666768 TI - Ultrastructural evaluation of the hybrid layer after cementation of fiber posts using adhesive systems with different curing modes. AB - This in vitro study evaluated the adhesive interface of intraradicular fiber glass posts and root dentin using scanning electron microscopy (SEM). Forty-eight single-rooted premolars were randomly divided into 6 groups consisting of chemical, dual, or light cured adhesive systems combined with either chemical or dual cure resin cements. Scanning electron microscopic analysis showed the best results for continuity, density and morphology of the hybrid layer and resin tags for the combination of a self-cure adhesive with self-cure cement resin, followed by a dual-cure adhesive with self-cure cement resin, and finally a light-cure adhesive with self-cure cement. For the dual-cure resin cement, the same relation may be observed. The apical third was the most critical region for evaluated the criteria for all combinations of materials (Kruskal-Wallis and Friedman tests; p<0.001). Generally, the simplification of steps in the adhesive system and the polymerization reaction of resin adhesives and cements produced a direct effect on the quality of the adhesive post/dentin substrate interface. PMID- 22666769 TI - Influence of apical foramen lateral opening and file size on cemental canal instrumentation. AB - Since instrumentation of the apical foramen has been suggested for cleaning and disinfection of the cemental canal, selection of the file size and position of the apical foramen have challenging steps. This study analyzed the influence of apical foramen lateral opening and file size can exert on cemental canal instrumentation. Thirty-four human maxillary central incisors were divided in two groups: Group 1 (n=17), without flaring, and Group 2 (n=17), with flaring with LA Axxess burs. K-files of increasing diameters were progressively inserted into the canal until binding at the apical foramen was achieved and tips were visible and bonded with ethyl cyanoacrylate adhesive. Roots/files set were cross-sectioned 5 mm from the apex. Apices were examined by scanning electron microscopy at *140 and digital images were captured. Data were analyzed statistically by Student's t test and Fisher's exact test at 5% significance level. SEM micrographs showed that 19 (56%) apical foramina emerged laterally to the root apex, whereas 15 (44%) coincided with it. Significantly more difficulty to reach the apical foramen was noted in Group 2. Results suggest that the larger the foraminal file size, the more difficult the apical foramen instrumentation may be in laterally emerged cemental canals. PMID- 22666770 TI - Three-dimensional image contribution for evaluation of operative procedural errors in endodontic therapy and dental implants. AB - Acceptable therapeutic protocol in dentistry depends on the outcomes obtained with follow up. Operative procedural errors (OPE) may occur and they represent risk factors able to compromise a tooth or a dental implant. The aim of this study was to detect the OPE in endodontically treated teeth and dental implants, using cone beam computed tomography (CBCT).Eight hundred and sixteen CBCT exams were performed between January 2009 and October 2010, and only those which presented endodontically treated teeth and/or dental implants were selected. The sample was as follows: 195 CBCT exams (n=200 teeth and 200 dental implants), 72 male, 123 female, with mean age of 51 years.In endodontically treated teeth, OPE included underfilling, overfilling, and root perforation; OPEin dental implants were thread exposures, contact with anatomical structures, and contact with adjacent teeth. Kolmogorov-Smirnov test was used for statistical analysis, with significance level set at alpha=0.05. Underfilling, overfilling, and root perforations were detected in 33.5%, 8% and 4.5% of the teeth, respectively. Dental implants with thread exposures, contact with important anatomical structures and contact with adjacent teeth were seen in 37.5%, 13% and 6.5% of the cases, respectively. OPE were detected in endodontically treated teeth and dental implants, and underfilling and thread exposures were the most frequent occurrences, respectively. PMID- 22666771 TI - Longitudinal clinical evaluation of post systems: a literature review. AB - In this survey, retrospective and prospective clinical studies dealing with cast post-and core and fiber posts were reviewed regarding the rate of survival of restorations and the most prevalent failures. Electronic searches of the literature were performed in MEDLINE by crossing the key words: "Fiber post and clinical study", "Fiber post and clinical evaluation", "Cast post-and-core and clinical study", and "Root post and retrospective survival study". The cut-off dates were December 1990 through the end of December 2010. Review of literature showed that several interrelated biological, mechanical, and aesthetic factors are involved in the survival rate of restorative procedures in endodontically treated teeth, and post selection should fulfill and optimize these factors. Data based on long-term clinical studies are essential for the general practitioner when making clinical decisions. An adequate selection of teeth and post system must be made, and a minimal amount of existing tooth substance should be removed. A ferrule must be present for safe indication of the fiber posts. Fiber glass posts have demonstrated good survival in clinical studies, with similar performance to cast-post-and cores. Metallic posts have good clinical survival, but the associated failures are mostly irreversible, unlike what happens with the glass fiber posts. PMID- 22666772 TI - Effects of chemical composition on the corrosion of dental alloys. AB - The aim of this study was to determine the effect of the oral environment on the corrosion of dental alloys with different compositions, using electrochemical methods. The corrosion rates were obtained from the current-potential curves and electrochemical impedance spectroscopy (EIS). The effect of artificial saliva on the corrosion of dental alloys was dependent on alloy composition. Dissolution of the ions occurred in all tested dental alloys and the results were strongly dependent on the general alloy composition. Regarding the alloys containing nickel, the Ni-Cr and Ni-Cr-Ti alloys released 0.62 mg/L of Ni on average, while the Co-Cr dental alloy released ions between 0.01 and 0.03 mg/L of Co and Cr, respectively.The open-circuit potential stabilized at a higher level with lower deviation (standard deviation: Ni-Cr-6Ti = 32 mV/SCE and Co-Cr = 54 mV/SCE). The potenciodynamic curves of the dental alloys showed that the Ni-based dental alloy with >70 wt% of Ni had a similar curve and the Co-Cr dental alloy showed a low current density and hence a high resistance to corrosion compared with the Ni based dental alloys. Some changes in microstructure were observed and this fact influenced the corrosion behavior for the alloys. The lower corrosion resistance also led to greater release of nickel ions to the medium. The quantity of Co ions released from the Co-Cr-Mo alloy was relatively small in the solutions. In addition, the quantity of Cr ions released into the artificial saliva from the Co Cr alloy was lower than Cr release from the Ni-based dental alloys. PMID- 22666773 TI - Correlation between maxillary central incisor crown morphology and mandibular dental arch form in normal occlusion subjects. AB - The aim of this study was to evaluate the correlation between the morphology of the mandibular dental arch and the maxillary central incisor crown. Cast models from 51 Caucasian individuals, older than 15 years, with optimal occlusion, no previous orthodontic treatment, featuring 4 of the 6 keys to normal occlusion by Andrews (the first being mandatory) were observed. The models were digitalized using a 3D scanner, and images of the maxillary central incisor and mandibular dental arch were obtained. These were printed and placed in an album below pre set models of arches and dental crowns, and distributed to 12 dental surgeons, who were asked to choose which shape was most in accordance with the models and crown presented. The Kappa test was performed to evaluate the concordance among evaluators while the chi-square test was used to verify the association between the dental arch and central incisor morphology, at a 5% significance level. The Kappa test showed moderate agreement among evaluators for both variables of this study, and the chi-square test showed no significant association between tooth shape and mandibular dental arch morphology. It may be concluded that the use of arch morphology as a diagnostic method to determine the shape of the maxillary central incisor is not appropriate. Further research is necessary to assess tooth shape using a stricter scientific basis. PMID- 22666774 TI - Abrasiveness of conventional and specific denture-cleansing dentifrices. AB - This study analyzed the weight loss and surface roughness caused in Plexiglass specimens by conventional dentifrices (Sorriso, Colgate and Close Up) and specific dentifrices used for cleaning of dentures (Corega and Dentu Creme). Plexiglass specimens were divided into 6 groups (n=6) including: a control (distilled water - DW) and experimental groups. Brushing was performed in a toothbrushing machine with a soft brush and a dentifrice suspension and DW according to different brushing times (50, 100, 200 and 250 min -18,000, 36,000, 72,000 and 90,000 cycles, respectively, calculated to correspond to 1, 2, 4 and 5 years of regular brushing). The results of weight loss and surface roughness were analyzed by ANOVA and Tukey's test at 5% significance level. In all tested times, the effect of DW was insignificant. Dentifrices differed significantly from DW in the initial period. Corega dentifrice caused greater mass loss in all studied times, followed by Close Up. Dentifrices resulted in a surface roughness similar to the DW at 50 min. In the other times, Sorriso, Colgate and Corega caused more surface roughness than DW. In conclusion, specific dentifrices caused larger mass loss and lower surface roughness as conventional dentifrice. PMID- 22666775 TI - Tooth wear in patients submitted to bariatric surgery. AB - Bariatric surgery may cause frequent vomiting episodes and gastroesophageal reflux, which promote the contact of gastric acids with the teeth leading to irreversible loss of tooth structure. The aim of this study was to assess prevalence of tooth wear in bariatric patients. One hundred and twenty-five patients were examined at a Public Hospital in Sao Luis, MA, Brazil, between July and October 2010, being patients who had already been submitted to the bariatric surgery at least 6 months previously (Bariatric group), morbidly obese patients who were on the waiting list for this surgery (Obese group) and patients who were waiting for ambulatory medical care in other sectors (Control group). The patients answered an investigative questionnaire and were clinically examined using the Basic Erosive Wear Examination (BEWE) scoring system, which allows the classification of the severity of noncarious dental lesions (NCDL) and evaluation of risk. All patients presented some degree of tooth wear at different levels. However, the presence of NCDL was associated with the group to which the patient belonged. The bariatric patients showed higher prevalence and a statistically significant level of risk with regard to NCDLs when compared with the other patients, followed by the obese and control groups. Reflux and vomiting did not seem to influence NCDL positively. PMID- 22666777 TI - Reestablishment of occlusion through overlay removable partial dentures: a case report. AB - Loss of posterior teeth may cause an imbalance in the stomatognathic system. Overlay removable partial dentures (ORPD) are a reversible and relatively inexpensive treatment for patients with severely worn teeth. This paper presents a treatment with ORPD in a 55-year-old male patient who had severe attrition in the maxillary and mandibular teeth, temporomandibular joint pain and reduced vertical dimension of occlusion (VDO). The treatment consisted in the reestablishment of the VDO using Lucia's jig, fabricating removable partial denture with reconstruction of the worn teeth without preparation. This therapy can be used as an alternative treatment to provide esthetic, function and stable occlusion in patients with severely worn teeth. PMID- 22666776 TI - Non-surgical retreatment of a failed apicoectomy without retrofilling using white mineral trioxide aggregate as an apical barrier. AB - Root-end resected teeth with persistent apical periodontitis are usually retreated surgically or a combination of non-surgical and surgical retreatment is employed. However, patients are sometimes unwilling to be subjected to a second surgical procedure. The apical barrier technique that is used for apical closure of immature teeth with necrotic pulps may be an alternative to non-surgically retreat a failed apicoectomy. Mineral trioxide aggregate (MTA) has become the material of choice in such cases because of its excellent biocompatibility, sealing ability and osseoinductive properties. This case report describes the non surgical retreatment of a failed apicoectomy with no attempt at retrofilling of a maxillary central incisor. White MTA was used to induce apical closure of the wide resected apical area. Four-year follow-up examination revealed an asymptomatic, fully functional tooth with a satisfactory healing of the apical lesion. White MTA apical barrier may constitute a reliable and efficient technique to non-surgically retreat teeth with failed root-end resection. The predictability of such a treatment is of great benefit for the patient who is unwilling to be submitted to a second surgical procedure. PMID- 22666778 TI - Physical training prevents body weight gain but does not modify adipose tissue gene expression. AB - The relationship of body weight (BW) with white adipose tissue (WAT) mass and WAT gene expression pattern was investigated in mice submitted to physical training (PT). Adult male C57BL/6 mice were submitted to two 1.5-h daily swimming sessions (T, N = 18), 5 days/week for 4 weeks or maintained sedentary (S, N = 15). Citrate synthase activity increased significantly in the T group (P < 0.05). S mice had a substantial weight gain compared to T mice (4.06 +/- 0.43 vs 0.38 +/- 0.28 g, P < 0.01). WAT mass, adipocyte size, and the weights of gastrocnemius and soleus muscles, lung, kidney, and adrenal gland were not different. Liver and heart were larger and the spleen was smaller in T compared to S mice (P < 0.05). Food intake was higher in T than S mice (4.7 +/- 0.2 vs 4.0 +/- 0.3 g/animal, P < 0.05) but oxygen consumption at rest did not differ between groups. T animals showed higher serum leptin concentration compared to S animals (6.37 +/- 0.5 vs 3.11 +/- 0.12 ng/mL). WAT gene expression pattern obtained by transcription factor adipocyte determination and differentiation-dependent factor 1, fatty acid synthase, malic enzyme, hormone-sensitive lipase, adipocyte lipid binding protein, leptin, and adiponectin did not differ significantly between groups. Collectively, our results showed that PT prevents BW gain and maintains WAT mass due to an increase in food intake and unchanged resting metabolic rate. These responses are closely related to unchanged WAT gene expression patterns. PMID- 22666779 TI - Evaluation of hemostatic changes using n thromboelastography after crystalloid or colloid fluid administration during major orthopedic surgery. AB - The effects of Ringer lactate, 6% hydroxyethyl starch (HES) (130/0.4) or 4% succinylated gelatin solutions on perioperative coagulability were measured by thromboelastography (TEG). Seventy-five patients (ASA I-III) who were to undergo major orthopedic procedures performed under epidural anesthesia were included in the study. Patients were randomly divided into three groups of 25 each for the administration of maintenance fluids: group RL (Ringer lactate), group HES (6% HES 130/0.4), and group JEL (4% gelofusine solution). Blood samples were obtained during the perioperative period before epidural anesthesia (t1, baseline), at the end of the surgery (t2), and 24 h after the operation (t3). TEG data, reaction time (R), coagulation time (K), angle value (alpha), and maximum amplitude (MA) were recorded. TEG parameters changed from normal values in all patients. In group RL, R and K times decreased compared to perioperative values while the alpha angle and MA increased (P < 0.05). In group HES, R and K times increased, however, the alpha angle and MA decreased (P < 0.05). In group JEL, R time increased (P < 0.05), but K time, alpha angle and MA did not change significantly. In the present study, RL, 6% HES (130/0.4) and 4% JEL solutions caused changes in the coagulation system of all patients as measured by TEG, but these changes remained within normal limits. PMID- 22666781 TI - Acoustic analyses of diadochokinesis in fluent and stuttering children. AB - OBJECTIVES: The purpose of the study was to acoustically compare the performance of children who do and do not stutter on diadochokinesis tasks in terms of syllable duration, syllable periods, and peak intensity. METHODS: In this case control study, acoustical analyses were performed on 26 children who stutter and 20 aged-matched normally fluent children (both groups stratified into preschoolers and school-aged children) during a diadochokinesis task: the repetition of articulatory segments through a task testing the ability to alternate movements. Speech fluency was assessed using the Fluency Profile and the Stuttering Severity Instrument. RESULTS: The children who stutter and those who do not did not significantly differ in terms of the acoustic patterns they produced in the diadochokinesis tasks. Significant differences were demonstrated between age groups independent of speech fluency. Overall, the preschoolers performed poorer. These results indicate that the observed differences are related to speech-motor age development and not to stuttering itself. CONCLUSIONS: Acoustic studies demonstrate that speech segment durations are most variable, both within and between subjects, during childhood and then gradually decrease to adult levels by the age of eleven to thirteen years. One possible explanation for the results of the present study is that children who stutter presented higher coefficients of variation to exploit the motor equivalence to achieve accurate sound production (i.e., the absence of speech disruptions). PMID- 22666780 TI - Protein turnover, amino acid requirements and recommendations for athletes and active populations. AB - Skeletal muscle is the major deposit of protein molecules. As for any cell or tissue, total muscle protein reflects a dynamic turnover between net protein synthesis and degradation. Noninvasive and invasive techniques have been applied to determine amino acid catabolism and muscle protein building at rest, during exercise and during the recovery period after a single experiment or training sessions. Stable isotopic tracers ((13)C-lysine, (15)N-glycine, 2H5 phenylalanine) and arteriovenous differences have been used in studies of skeletal muscle and collagen tissues under resting and exercise conditions. There are different fractional synthesis rates in skeletal muscle and tendon tissues, but there is no major difference between collagen and myofibrillar protein synthesis. Strenuous exercise provokes increased proteolysis and decreased protein synthesis, the opposite occurring during the recovery period. Individuals who exercise respond differently when resistance and endurance types of contractions are compared. Endurance exercise induces a greater oxidative capacity (enzymes) compared to resistance exercise, which induces fiber hypertrophy (myofibrils). Nitrogen balance (difference between protein intake and protein degradation) for athletes is usually balanced when the intake of protein reaches 1.2 g . kg(-1) . day(-1) compared to 0.8 g . kg(-1) . day(-1) in resting individuals. Muscular activities promote a cascade of signals leading to the stimulation of eukaryotic initiation of myofibrillar protein synthesis. As suggested in several publications, a bolus of 15-20 g protein (from skimmed milk or whey proteins) and carbohydrate (+/- 30 g maltodextrine) drinks is needed immediately after stopping exercise to stimulate muscle protein and tendon collagen turnover within 1 h. PMID- 22666782 TI - Current practices in the management of patients with ureteral calculi in the emergency room of a university hospital. AB - OBJECTIVE: Urinary lithiasis is a common disease. The aim of the present study is to assess the knowledge regarding the diagnosis, treatment and recommendations given to patients with ureteral colic by professionals of an academic hospital. MATERIALS AND METHODS: Sixty-five physicians were interviewed about previous experience with guidelines regarding ureteral colic and how they manage patients with ureteral colic in regards to diagnosis, treatment and the information provided to the patients. RESULTS: Thirty-six percent of the interviewed physicians were surgeons, and 64% were clinicians. Forty-one percent of the physicians reported experience with ureterolithiasis guidelines. Seventy-two percent indicated that they use noncontrast CT scans for the diagnosis of lithiasis. All of the respondents prescribe hydration, primarily for the improvement of stone elimination (39.3%). The average number of drugs used was 3.5. The combination of nonsteroidal anti-inflammatory drugs and opioids was reported by 54% of the physicians (i.e., 59% of surgeons and 25.6% of clinicians used this combination of drugs) (p = 0.014). Only 21.3% prescribe alpha blockers. CONCLUSION: Reported experience with guidelines had little impact on several habitual practices. For example, only 21.3% of the respondents indicated that they prescribed alpha blockers; however, alpha blockers may increase stone elimination by up to 54%. Furthermore, although a meta-analysis demonstrated that hydration had no effect on the transit time of the stone or on the pain, the majority of the physicians reported that they prescribed more than 500 ml of fluid. Dipyrone, hyoscine, nonsteroidal anti-inflammatory drugs, and opioids were identified as the most frequently prescribed drug combination. The information regarding the time for the passage of urinary stones was inconsistent. The development of continuing education programs regarding ureteral colic in the emergency room is necessary. PMID- 22666783 TI - Epidermal growth factor receptor and KRAS mutations in Brazilian lung cancer patients. AB - OBJECTIVE: Epidermal growth factor receptor is involved in the pathogenesis of non-small cell lung cancer and has recently emerged as an important target for molecular therapeutics. The KRAS oncogene also plays an important role in the development of lung cancer. The aim of this study was to evaluate the frequency of epidermal growth factor receptor and KRAS mutations in a population of Brazilian patients with non-small cell lung cancer. METHODS: A total of 207 specimens from Brazilian patients with non-small cell lung cancer were analyzed for activating epidermal growth factor receptor and KRAS somatic mutations, and their associations with clinicopathological characteristics (including age, gender, ethnicity, smoking habits, and histological subtype) were examined. RESULTS: We identified 63 cases (30.4%) with epidermal growth factor receptor mutations and 30 cases (14.6%) with KRAS mutations. The most frequent epidermal growth factor receptor mutation we detected was a deletion in exon 19 (60.3%, 38 patients), followed by an L858R amino acid substitution in exon 21 (27%, 17 patients). The most common types of KRAS mutations were found in codon 12. There were no significant differences in epidermal growth factor receptor or KRAS mutations by gender or primary versus metastatic lung cancer. There was a higher prevalence of KRAS mutations in the non-Asian patients. Epidermal growth factor receptor mutations were more prevalent in adenocarcinomas than in non adenocarcinoma histological types. Being a non-smoker was significantly associated with the prevalence of epidermal growth factor receptor mutations, but the prevalence of KRAS mutations was significantly associated with smoking. CONCLUSIONS: This study is the first to examine the prevalence of epidermal growth factor receptor and KRAS mutations in a Brazilian population sample with non-small cell lung cancer. PMID- 22666784 TI - Thymopoiesis and regulatory T cells in healthy children and adolescents. AB - OBJECTIVES: The purpose of this study was to investigate the association between T cell receptor excision circle levels in peripheral blood mononuclear cells and regulatory T cells that co-express CD25 and Foxp3 in healthy children and adolescents of different ages. MATERIALS AND METHODS: The quantification of signal-joint T-cell receptor excision circle levels in the genomic DNA of peripheral blood mononuclear cells was performed using real-time quantitative PCR. The analysis of CD4, CD8, CD25, and Foxp3 expression was performed using flow cytometry. RESULTS: Ninety-five healthy controls (46 females and 49 males) ranging in age from 1 to 18 years were analyzed. The mean T-cell receptor excision circle count in all individuals was 89.095 +/- 36.790 T-cell receptor excision circles per microgram of DNA. There was an inverse correlation between T cell receptor excision circles counts and age (r = -0.846; p<0.001) as well as between the proportion of CD4(+)CD25(+)Foxp3(+) T cells and age (r = -0.467; p = 0.04). In addition, we observed a positive correlation between the amount of CD4(+)CD25(+)Foxp3(+) T cells and the amount of T-cell receptor excision circles per microgram of DNA in individuals of all ages (r = -0.529; p = 0.02). CONCLUSIONS: In this study, we observed a decrease in the thymic function with age based on the fact that the level of T-cell receptor excision circles in the peripheral blood positively correlated with the proportion of regulatory T cells in healthy children and adolescents. These findings indicate that although T-cell receptor excision circles and regulatory T cells levels decrease with age, homeostasis of the immune system and relative regulatory T cells population levels are maintained in the peripheral blood. PMID- 22666785 TI - Shewanella infection of snake bites: a twelve-year retrospective study. AB - OBJECTIVE: Infections of snake bite wounds by Shewanella are rarely discussed in the medical literature. This study aims to characterize the presentation and management of Shewanella infections in snake bite wounds. METHOD: We retrospectively investigated the microbiology, clinical features, and outcomes of patients with Shewanella infected snake bite wounds admitted to a tertiary medical center from January 1998 to December 2009. RESULTS: Ten patients with Shewanella-infected snake bite wounds were identified. All of the snake bites were caused by cobras. The majority of patients had moderate to severe local envenomation and polymicrobial infections. Shewanella isolates are susceptible to ampicillin-sulbactam, piperacillin-tazobactam, third-and fourth-generation cephalosporins, carbapenems, aminoglycosides, and quinolones but are resistant to penicillin and cefazolin. All of the patients examined had favorable outcomes. CONCLUSION: It is recommended that Shewanella infection be considered in snake bite patients, especially when patients present with moderate to severe local envenomation. PMID- 22666786 TI - A comparison of CA125, HE4, risk ovarian malignancy algorithm (ROMA), and risk malignancy index (RMI) for the classification of ovarian masses. AB - OBJECTIVE: Differentiation between benign and malignant ovarian neoplasms is essential for creating a system for patient referrals. Therefore, the contributions of the tumor markers CA125 and human epididymis protein 4 (HE4) as well as the risk ovarian malignancy algorithm (ROMA) and risk malignancy index (RMI) values were considered individually and in combination to evaluate their utility for establishing this type of patient referral system. METHODS: Patients who had been diagnosed with ovarian masses through imaging analyses (n = 128) were assessed for their expression of the tumor markers CA125 and HE4. The ROMA and RMI values were also determined. The sensitivity and specificity of each parameter were calculated using receiver operating characteristic curves according to the area under the curve (AUC) for each method. RESULTS: The sensitivities associated with the ability of CA125, HE4, ROMA, or RMI to distinguish between malignant versus benign ovarian masses were 70.4%, 79.6%, 74.1%, and 63%, respectively. Among carcinomas, the sensitivities of CA125, HE4, ROMA (pre-and post-menopausal), and RMI were 93.5%, 87.1%, 80%, 95.2%, and 87.1%, respectively. The most accurate numerical values were obtained with RMI, although the four parameters were shown to be statistically equivalent. CONCLUSION: There were no differences in accuracy between CA125, HE4, ROMA, and RMI for differentiating between types of ovarian masses. RMI had the lowest sensitivity but was the most numerically accurate method. HE4 demonstrated the best overall sensitivity for the evaluation of malignant ovarian tumors and the differential diagnosis of endometriosis. All of the parameters demonstrated increased sensitivity when tumors with low malignancy potential were considered low-risk, which may be used as an acceptable assessment method for referring patients to reference centers. PMID- 22666787 TI - Spinocerebellar ataxias: genotype-phenotype correlations in 104 Brazilian families. AB - OBJECTIVE: Spinocerebellar ataxias are neurodegenerative disorders involving the cerebellum and its connections. There are more than 30 distinct subtypes, 16 of which are associated with an identified gene. The aim of the current study was to evaluate a large group of patients from 104 Brazilian families with spinocerebellar ataxias. METHODS: We studied 150 patients from 104 families with spinocerebellar ataxias who had received molecular genetic testing for spinocerebellar ataxia types 1, 2, 3, 6, 7, 8, 10, 12, 17, and dentatorubral pallidoluysian atrophy. A statistical analysis of the results was performed using basic descriptive statistics and the correlation coefficient (r), Student's t test, chi-square test, and Yates' correction. The statistical significance level was established for p-values <0.05. RESULTS: The results show that the most common subtype was spinocerebellar ataxia 3, which was followed by spinocerebellar ataxia 10. Moreover, the comparison between patients with spinocerebellar ataxia 3, spinocerebellar ataxia 10, and other types of spinocerebellar ataxia revealed distinct clinical features for each type. In patients with spinocerebellar ataxia 3, the phenotype was highly pleomorphic, although the most common signs of disease included cerebellar ataxia (CA), ophthalmoplegia, diplopia, eyelid retraction, facial fasciculation, pyramidal signs, and peripheral neuropathy. In patients with spinocerebellar ataxia 10, the phenotype was also rather distinct and consisted of pure cerebellar ataxia and abnormal saccadic eye movement as well as ocular dysmetria. Patients with spinocerebellar ataxias 2 and 7 presented highly suggestive features of cerebellar ataxia, including slow saccadic ocular movements and areflexia in spinocerebellar ataxia 2 and visual loss in spinocerebellar ataxia 7. CONCLUSIONS: Spinocerebellar ataxia 3 was the most common subtype examined, followed by spinocerebellar ataxia 10. Patients with spinocerebellar ataxia 2 and 7 demonstrated highly suggestive features, whereas the phenotype of spinocerebellar ataxia 3 patients was highly pleomorphic and spinocerebellar ataxia 10 patients exhibited pure cerebellar ataxia. Epilepsy was absent in all of the patients with spinocerebellar ataxia 10 in this series. PMID- 22666788 TI - Longitudinal reference ranges for fetal ultrasound biometry in twin pregnancies. AB - OBJECTIVE: The purpose of this study was to establish longitudinal reference ranges for fetal ultrasound biometry measurements and growth parameters in twin pregnancies. METHOD: A total of 200 uncomplicated twin pregnancies before 21 weeks of gestation were recruited for this prospective, longitudinal study. Women who abandoned follow-up, pregnancies with unknown outcomes or pregnancies with complications were excluded. Ultrasound scans were performed every three weeks, and biparietal and occipitofrontal diameters, head and abdominal circumferences, and femur diaphysis length measurements were obtained for each fetus at each visit. Estimated fetal weight, biparietal/occipitofrontal diameter, head circumference/abdominal circumference, and femur diaphysis length/abdominal circumference ratios were also calculated. Multilevel regression analysis was performed on normalized data. RESULTS: A total of 807 ultrasound examinations were performed in 125 twin pregnancies between 14 and 38 weeks of gestation (6.5 +/- 1.4 scans/pregnancy). Regression analysis demonstrated significant correlations for all variables with gestational age, namely log of the biparietal diameter (r = 0.98), log of the occipitofrontal diameter (r = 0.98), log of the head circumference (r = 0.99), log of the abdominal circumference (r = 0.98), square root of the femur length (r = 0.99), log of the estimated fetal weight (r = 0.99), biparietal/occipitofrontal ratio (r = -0.11), head/abdomen circumference ratio (r = -0.56), and log of the femur length/abdominal circumference ratio (r = 0.61). Values corresponding to the 10(th), 50(th), and 90(th) percentiles for estimated fetal weight at 28, 32, and 36 weeks, respectively, were as follows: 937, 1,096, 1,284 g; 1,462, 1,720, 2,025 g; and 2,020, 2,399, 2,849 g. CONCLUSION: In twin pregnancies, fetal ultrasound biometry measurements and growth parameters show a significant correlation with gestational age. PMID- 22666789 TI - Metabolic assessment of elderly men with urolithiasis. AB - OBJECTIVE: To assess the presence of metabolic disorders in elderly men with urolithiasis. METHODS: We performed a case-control study. The inclusion criteria were as follows: (1) men older than 60 years of age and either (2) antecedent renal colic or an incidental diagnosis of urinary lithiasis after age 60 (case arm) or (3) no antecedent renal colic or incidental diagnosis of urolithiasis (control arm). Each individual underwent an interview, and those who were selected underwent all clinical protocol examinations: serum levels of total and ionized calcium, uric acid, phosphorus, glucose, urea, creatinine and parathyroid hormone, urine culture, and analysis of 24-hour urine samples (levels of calcium, citrate, creatinine, uric acid and sodium, pH and urine volume). Each case arm patient underwent two complete metabolic urinary investigations, whereas each control arm individual underwent one examination. ClinicalTrials.gov: NCT01246531. RESULTS: A total of 51 subjects completed the clinical investigation: 25 in the case arm and 26 in the control arm. In total, 56% of the case arm patients had hypocitraturia (vs. 15.4% in the control arm; p = 0.002). Hypernatriuria was detected in 64% of the case arm patients and in 30.8% of the controls (p = 0.017). CONCLUSION: Hypocitraturia and hypernatriuria are the main metabolic disorders in elderly men with urolithiasis. PMID- 22666790 TI - A comparative radiographic investigation of femoroacetabular impingement in young patients with and without hip pain. AB - OBJECTIVE: To compare the existence of radiographic abnormalities in two groups of patients, those with and without hip pain. METHODS: A total 222 patients were evaluated between March 2007 and April 2009; 122 complained of groin pain, and 100 had no symptoms. The individuals in both groups underwent radiographic examinations of the hip using the following views: anteroposterior, Lequesne false profile, Dunn, Dunn 45o, and Ducroquet. RESULTS: A total of 1110 radiographs were evaluated. Female patients were prevalent in both groups (52% symptomatic, 58% asymptomatic). There were statistically significant differences between the groups in age (p<0.0001), weight (p = 0.002) and BMI (p = 0.006). The positive findings in the group with groin pain consisted of the presence of a bump on the femoral head in the anteroposterior view (p<0.0001) or in the Dunn 45o view (p = 0.008). The difference in the a angle in the anteroposterior, Dunn, Dunn 45o, and Ducroquet views for all of the cases studied was p,0.0001. The joint space measurement differed significantly between groups in the Lequesne view (p = 0.007). The Lequesne anteversion angle (rho) and the femoral offset measurement also differed significantly (p = 0.005 and p = 0.0001, respectively). CONCLUSIONS: We conclude that the best views for diagnosing a femoroacetabular impingement are the anteroposterior pelvic orthostatic, the Dunn 45o, and the Ducroquet views. The following findings correlated with hip pain: a decrease in the femoral offset, an increase in the alpha angle, an increase in the Lequesne rho angle, a decrease in the CE angle of Wiberg, a thinner articular space and the presence of a bump on the femoral head-neck transition. PMID- 22666791 TI - The use of nasal dilator strips as a placebo for trials evaluating continuous positive airway pressure. AB - OBJECTIVES: The aim of the current study was to compare the objective and subjective effects of continuous positive airway pressure to the use of nasal dilator strips in patients with acromegaly and moderate to severe obstructive sleep apnea. METHODS: We studied 12 patients with acromegaly and moderate to severe obstructive sleep apnea (male/ females = 8/4, age = 52 +/- 8 ys, body mass index = 33.5 +/- 4.6 Kg/m(2), apnea-hypopnea index = 38 +/- 14 events/h) who had been included in a randomized, crossover study to receive three months of treatment with continuous positive airway pressure and nasal dilator strips. All patients were evaluated at study entry and at the end of each treatment by polysomnography, and Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index and treatment satisfaction questionnaires. ClinicalTrials.gov: NCT01265121 RESULTS: The apnea-hypopnea index values decreased significantly with continuous positive airway pressure treatment but did not change with the use of nasal dilator strips. All of the subjective symptoms improved with both treatments, but these improvements were significantly greater with continuous positive airway pressure than with the nasal dilator strips. CONCLUSION: The use of nasal dilator strips had a much smaller effect on the severity of obstructive sleep apnea in patients with acromegaly and moderate to severe obstructive sleep apnea in comparison to the use of continuous positive airway pressure. Moreover, the improvement in several subjective parameters without any significant objective improvement in obstructive sleep apnea resulting from the use of nasal dilator strips is compatible with a placebo effect. PMID- 22666792 TI - Obese elderly women exhibit low postural stability: a novel three-dimensional evaluation system. AB - OBJECTIVE: The aim of this study was to evaluate the multisegmental static postural balance of active eutrophic and obese elderly women using a three dimensional system under different sensory conditions. METHODS: A cross-sectional study was conducted on 31 elderly women (16 eutrophic and 15 obese) aged 65 to 75 years. The following anthropometric measurements were obtained: weight, height, waist and hip circumference, and handgrip strength. The physical activity level was evaluated using the International Physical Activity Questionnaire. Body composition was measured using the deuterium oxide dilution technique. The Polhemus((r)) Patriot (three-dimensional) equipment was used to measure the parameters of postural balance along the anteroposterior and laterolateral axes. The data acquisition involved one trial of 60 s to test the limit of stability and four trials of 90 s each under the following conditions: (1) eyes open, stable surface; (2) eyes closed, stable surface; (3) eyes open, unstable surface; and (4) eyes closed, unstable surface. RESULTS: For the limit of stability, significant differences were observed in the maximum anteroposterior and laterolateral displacement (p<0.01) and in the parameter maximum anteroposterior displacement in the eyes closed stable surface condition (p<0.01) and maximum anteroposterior and laterolateral displacement in the eyes open unstable surface (p<0.01 and p = 0.03) and eyes closed unstable surface (p<0.01 and p<0.01) conditions. CONCLUSIONS: Obese elderly women exhibited a lower stability limit (lower sway area) compared with eutrophic women, leaving them more vulnerable to falls. PMID- 22666793 TI - Foxp3 expression is associated with aggressiveness in differentiated thyroid carcinomas. AB - OBJECTIVES: Forkhead box P3 (FoxP3) expression has been observed in human cancer cells but has not yet been reported in thyroid cells. We investigated the prognostic significance of both FoxP3 expression and intratumoral FoxP3(+) lymphocyte infiltration in differentiated thyroid carcinoma cells. METHODS: We constructed a tissue microarray with 385 thyroid tissues, including 266 malignant tissues (from 253 papillary thyroid carcinomas and 13 follicular carcinomas), 114 benign lesions, and 5 normal thyroid tissues. RESULTS: We determined the expression of FoxP3 in both tumor cells and tumor-infiltrating lymphocytes using immunohistochemical techniques. Cellular expression of FoxP3 was evident in 71% of benign and 91.9% of malignant tissues. The nuclear and cytoplasmic expression patterns were quantified separately. A multivariate logistic regression analysis indicated that cytoplasmic FoxP3 expression is an independent risk factor for thyroid malignancy. Cytoplasmic FoxP3 staining was inversely correlated with patient age. Nuclear FoxP3 staining was more intense in younger patients and in tumors presenting with metastasis at diagnosis. FoxP3(+) lymphocytes were more frequent in tumors smaller than 2 cm, those without extrathyroidal invasion, and in patients with concurrent chronic lymphocytic thyroiditis. CONCLUSIONS: We demonstrated FoxP3 expression in differentiated thyroid carcinoma cells and found evidence that this expression may exert an important influence on several features of tumor aggressiveness. PMID- 22666794 TI - Tension cost correlates with mechanical and biochemical parameters in different myocardial contractility conditions. AB - OBJECTIVES: Tension cost, the ratio of myosin ATPase activity to tension, reflects the economy of tension development in the myocardium. To evaluate the mechanical advantage represented by the tension cost, we studied papillary muscle contractility and the activity of myosin ATPase in the left ventricles in normal and pathophysiological conditions. METHODS: Experimental protocols were performed using rat left ventricles from: (1) streptozotocin-induced diabetic and control Wistar rats; (2) N-nitro-L-arginine methyl ester (L-NAME) hypertensive and untreated Wistar rats; (3) deoxycorticosterone acetate (DOCA) salt-treated, nephrectomized and salt- and DOCA-treated rats; (4) spontaneous hypertensive rats (SHR) and Wistar Kyoto (WKY) rats; (5) rats with myocardial infarction and shamoperated rats. The isometric force, tetanic tension, and the activity of myosin ATPase were measured. RESULTS: The results obtained from infarcted, diabetic, and deoxycorticosterone acetate-salt-treated rats showed reductions in twitch and tetanic tension compared to the control and sham-operated groups. Twitch and tetanic tension increased in the N-nitro-L-arginine methyl ester treated rats compared with the Wistar rats. Myosin ATPase activity was depressed in the infarcted, diabetic, and deoxycorticosterone acetate salt-treated rats compared with control and sham-operated rats and was increased in N-nitro-L arginine methyl ester-treated rats. These parameters did not differ between SHR and WKY rats. In the studied conditions (e.g., post-myocardial infarction, deoxycorticosterone acetate salt-induced hypertension, chronic N-nitro-L-arginine methyl ester treatment, and streptozotocin-induced diabetes), a positive correlation between force or plateau tetanic tension and myosin ATPase activity was observed. CONCLUSION: Our results suggest that the myocardium adapts to force generation by increasing or reducing the tension cost to maintain myocardial contractility with a better mechanical advantage. PMID- 22666795 TI - Acute and subchronic toxicological evaluation of Echinophora platyloba DC (Apiaceae) total extract in Wistar rats. AB - OBJECTIVE: Echinophora platyloba DC is a widely used herbal medicine and food seasoning in Iran. It is claimed to exert antimicrobial, antifungal, and antispasmodic effects. Despite the prevalent use of this plant as a food and medicine, there are no reports on its possible toxic effects. To evaluate the safety of E. platyloba, we tested its acute and sub-chronic toxicity in male and female Wistar rats. METHODS: Rats were orally treated with four different single doses of E. platyloba total extract and screened for signs of toxicity two weeks after administration. In the sub-chronic toxicity study, E. platyloba was administered for 45 days. Mortality, clinical signs, body weight changes, hematological and biochemical parameters, gross findings, organ weights, and histological markers were monitored during the study. RESULTS: We found no mortality and no abnormality in clinical signs, body weight, or necropsy findings in any of the animals in the acute study. The results of the subchronic study showed no significant difference in hematological parameters in either sex. There was a significant increase in lactate dehydrogenase in the female groups. A significant increase in the relative lung weight of female rats was noted at 500 mg/kg. Histopathological examinations revealed intra-alveolar hemorrhage in the male rats (500 mg/kg). In the females, congestion of the alveolar capillaries (at 500 mg/kg) and liver bridging necrosis (at 200 mg/kg) were significantly increased. CONCLUSION: The no observed adverse effect level of E. platyloba was determined to be 200 and 50 mg/kg for male and female rats, respectively. PMID- 22666796 TI - Hypoxia/reoxygenation-induced myocardial lesions in newborn piglets are related to interindividual variability and not to oxygen concentration. AB - OBJECTIVE: Evaluation of myocardial histological changes in an experimental animal model of neonatal hypoxia-reoxygenation. METHODS: Normocapnic hypoxia was induced in 40 male Landrace/Large White piglets. Reoxygenation was initiated when the animals developed bradycardia (HR <60 beats/min) or severe hypotension (MAP <15 mmHg). The animals were divided into four groups based on the oxygen (O(2)) concentration used for reoxygenation; groups 1, 2, 3, and 4 received 18%, 21%, 40%, and 100% O(2), respectively. The animals were further classified into five groups based on the time required for reoxygenation: A: fast recovery (<15 min); B: medium recovery (15-45 min); C: slow recovery (45-90 min); D: very slow recovery (>90 min), and E: nine deceased piglets. RESULTS: Histology revealed changes in all heart specimens. Interstitial edema, a wavy arrangement, hypereosinophilia and coagulative necrosis of cardiomyocytes were observed frequently. No differences in the incidence of changes were observed among groups 1-4, whereas marked differences regarding the frequency and the degree of changes were found among groups A-E. Coagulative necrosis was correlated with increased recovery time: this condition was detected post-asphyxia in 14%, 57%, and 100% of piglets with fast, medium, and slow or very slow recovery rates, respectively. CONCLUSIONS: The significant myocardial histological changes observed suggest that this experimental model might be a reliable model for investigating human neonatal cardiac hypoxia-related injury. No correlation was observed between the severity of histological changes and the fiO(2) used during reoxygenation. Severe myocardial changes correlated strictly with recovery time, suggesting an unreported individual susceptibility of myocardiocytes to hypoxia, possibly leading to death after the typical time-sequence of events. PMID- 22666797 TI - Articles with short titles describing the results are cited more often. AB - OBJECTIVE: The aim of this study was to evaluate some features of article titles from open access journals and to assess the possible impact of these titles on predicting the number of article views and citations. METHODS: Research articles (n = 423, published in October 2008) from all Public Library of Science (PLoS) journals and from 12 Biomed Central (BMC) journals were evaluated. Publication metrics (views and citations) were analyzed in December 2011. The titles were classified according to their contents, namely methods-describing titles and results-describing titles. The number of title characters, title typology, the use of a question mark, reference to a specific geographical region, and the use of a colon or a hyphen separating different ideas within a sentence were analyzed to identify predictors of views and citations. A logistic regression model was used to identify independent title characteristics that could predict citation rates. RESULTS: Short-titled articles had higher viewing and citation rates than those with longer titles. Titles containing a question mark, containing a reference to a specific geographical region, and that used a colon or a hyphen were associated with a lower number of citations. Articles with results describing titles were cited more often than those with methods-describing titles. After multivariate analysis, only a low number of characters and title typology remained as predictors of the number of citations. CONCLUSIONS: Some features of article titles can help predict the number of article views and citation counts. Short titles presenting results or conclusions were independently associated with higher citation counts. The findings presented here could be used by authors, reviewers, and editors to maximize the impact of articles in the scientific community. PMID- 22666798 TI - Intraoperative diagnosis of cystobiliary communications of hydatid liver cysts. PMID- 22666799 TI - Use of hepatitis C-positive donors in transplantation. PMID- 22666800 TI - A new technique for the correction of hypoplastic left heart syndrome. PMID- 22666801 TI - Early diagnosis of acute kidney injury in a critically ill patient using a combination of blood and urinary physicochemical parameters. PMID- 22666802 TI - Epigastric heteropagus conjoined twins: two case studies and associated DNA analysis. PMID- 22666803 TI - Modified Nissen fundoplication: laparoscopic antireflux surgery after Roux-en-Y gastric bypass for obesity. PMID- 22666804 TI - Surgical correction of hypoplastic left heart syndrome: a new approach. PMID- 22666806 TI - Crack in Brazil: a public health emergency. PMID- 22666807 TI - Meta-analysis of the prevalence of physical inactivity among Brazilian adolescents. AB - A systematic review and meta-analysis were carried out to investigate the prevalence of physical inactivity among adolescents in Brazil. We identified articles that had been published up to August 2010 and the search was conducted using six electronic databases. We did not enforce any search limitations. Forest plot-type graphs were generated using the prevalence of physical inactivity stratified by region and sex. Meta-regression models were fitted to identify possible sources of heterogeneity in the prevalence estimates. Of the 1,496 articles initially identified, 37 were deemed appropriate for the systematic review. Prevalence rates ranged from 2% to 80% for male and from 14% to 91% for female subgroups. The lowest prevalence rates of physical inactivity were found to be for the Southern region, whereas the highest rates were observed in the North-Northeast. The methods employed to evaluate physical inactivity in Brazilian adolescents also differed among the studies. This variation demonstrates the need for standardised and validated methods of measuring physical activity in epidemiological investigation. PMID- 22666808 TI - [Use of medications by elderly Brazilians according to age: a postal survey]. AB - The objective of this study was to evaluate factors associated with use of medicines by the elderly. A national postal survey was conducted with a random sample of 3,000 elderly individuals selected from the registry of the Brazilian National Social Security Institute. The study estimated the prevalence and average number of medicines used in the 15 days prior to the survey, according to age bracket. Prevalence of use of medication was 83.0%: 78.8% in the 60-69 year bracket and 87.3% in individuals 70 years or older (p < 0.05). Older elders had taken an average of 4.4 drugs, as compared to 3.3 among younger elders. Drugs for the cardiovascular system were the most widely used. Age 70 years and older, female gender, poor self-rated health, interruption of routine daily activities, six or more medical visits in the previous year, private health insurance, and reporting of four or more illnesses were independently associated with use of medications (p < 0.05). The results expand the knowledge on use of medications among elderly Brazilians, emphasizing the need to improve pharmaceutical care focused on this subgroup of the population. PMID- 22666809 TI - [Asthma and associated factors in students 13 and 14 years of age in Sao Luis, Maranhao State, Brazil]. AB - The aim of this study was to estimate the prevalence of asthma and associated factors among students 13 and 14 years of age in Sao Luis, Maranhao State, Brazil. A cross-sectional study was conducted using the questionnaire developed by ISAAC (International Study of Asthma and Allergies in Childhood) and an additional questionnaire from July 2008 to May 2009, including 3,069 adolescents. Asthma prevalence (wheezing in the previous 12 months) was 12.7%, lifetime prevalence was 32.4%, 3.9% reported difficulty speaking due to wheezing, and 9.8% reported wheezing after exercise. In the multivariate analysis, factors associated with increased asthma prevalence were family history of asthma, respiratory infection and wheezing in early life, eczema, allergic rhinitis, and passive smoking. Asthma prevalence was lower than for Brazil as a whole. Factors most strongly associated with asthma prevalence in these adolescents were family history of asthma (PR = 3.86), wheezing in early childhood (PR = 4.58), and allergic rhinitis (PR = 3.21). PMID- 22666810 TI - [Maternal mortality and impact of dengue in Southeast Brazil: an ecological study, 2001-2005]. AB - The aim of this study was to explore the distribution of reproductive outcomes following dengue virus infection during pregnancy (2001-2005). An ecological epidemiological study was conducted in all counties with more than 80,000 inhabitants in Southeast Brazil. The study explored the correlation between dengue incidence rates in women 15-39 years of age and selected mortality indicators (maternal, fetal, perinatal, neonatal, early neonatal, and infant) in these counties, and Spearman correlation coefficients were calculated. A positive correlation was observed between median dengue incidence in women 15-39 years of age and median maternal mortality (r = 0.88; 95%CI: 0.51; 1.00), with a determination coefficient R2 = 0.78. The correlation between dengue incidence in childbearing-age women and reproductive outcomes in Southeast Brazil suggests that dengue infection during pregnancy can negatively impact its outcome and increase maternal mortality. PMID- 22666811 TI - [Spatial evolution of cardiovascular mortality in Parana State, Brazil: 1989-1991 and 2006-2008]. AB - This ecological study aimed to describe the spatial distribution of cardiovascular mortality in Parana State, Brazil (1989-1991 and 2006-2008) and its correlation with socioeconomic variables, using mortality data from the DATASUS database and population data from IBGE. Mortality rates were adjusted by the local empirical Bayesian method. Correlation analysis used the Moran I index and Spearman coefficient. There were no significant correlations or spatial dependence between mortality and socioeconomic variables. Mortality was higher in males in both periods. Cardiovascular mortality declined from 1989-1991 to 2006 2008 and was higher in females. Construction of thematic maps allowed visualization of the regions with highest cardiovascular risk. The decrease in mortality can be partially explained by expanded access to health services and improved living conditions and income. PMID- 22666812 TI - [Factors associated with preterm birth in Campina Grande, Paraiba State, Brazil: a case-control study]. AB - A case-control study (2008-2009) analyzed risk factors for preterm birth in the city of Campina Grande, Paraiba State, Brazil. A total of 341 preterm births and 424 controls were included. A multiple logistic regression model was used. Risk factors for preterm birth were: previous history of preterm birth (OR = 2.32; 95%CI: 1.25-4.29), maternal age (OR = 2.00; 95%CI: 1.00-4.03), inadequate prenatal care (OR = 2.15; 95%CI: 1.40-3.27), inadequate maternal weight gain (OR = 2.33; 95%CI: 1.45-3.75), maternal physical injury (OR = 2.10; 95%CI: 1.22 3.60), hypertension with eclampsia (OR = 17.08; 95%CI: 3.67-79.43) and without eclampsia (OR = 6.42; 95%CI: 3.50-11.76), hospitalization (OR = 5.64; 95%CI: 3.47 9.15), altered amniotic fluid volume (OR = 2.28; 95%CI: 1.32-3.95), vaginal bleeding (OR = 1.54; 95%CI: 1.01-2.34), and multiple gestation (OR = 22.65; 95%CI: 6.22-82.46). High and homogeneous prevalence of poverty and low maternal schooling among both cases and controls may have contributed to the fact that socioeconomic variables did not remain significantly associated with preterm birth. PMID- 22666813 TI - [Personality factors as predictors of alcohol consumption by university students]. AB - This study aimed to verify differences in personality factors between abstainers and drinkers and between individuals with higher versus lower levels of alcohol consumption in the previous three months, and to test the predictive power of factors for any lifetime alcohol consumption and for at least monthly alcohol consumption. A total of 169 university students participated, of whom 66.7% were women, with a mean age of 21.2 years. Lifetime alcohol consumption was 90.1%; 42.3% had consumed at least twice in the previous three months; and 57.7% consumed alcohol at least monthly. Participants with less frequent consumption in the previous three months showed higher mean scores for personality factors involving socialization and achievement, while those that consumed more frequently scored higher on extroversion. A predictive model showed that increments in extroversion contributed to increased odds of drinking alcohol, while increments in achievement decreased the odds of drinking. Personality characteristics were able to distinguish between different groups of drinkers and predict the frequency of alcohol consumption. PMID- 22666814 TI - [Self-perceived oral health among elderly individuals in a medium-sized city in Northeast Brazil]. AB - This study focused on self-perceived oral health of the elderly and associated variables. The sample consisted of 321 functionally independent individuals 60 years or older living in Parnaiba, Piaui State, Brazil. Oral examinations were performed and questionnaires were applied during home visits. The elderly presented poor oral health, with mean DMFT 29.41 (SD = 4.10). However, their self perceived oral health was positive, with 52% showing high scores according to the Geriatric Oral Health Assessment Index (GOHAI). Multivariate analysis showed that predictors of self-perceived oral health included the need for upper prostheses, oral mucosal lesions, and self-rated oral health. The most important predictor was self-rated oral health, with a weight of 20% variation in self-perceived oral health. In conclusion, subjective measurement of oral health in the elderly is less associated with their actual clinical status and more with other subjective factors. PMID- 22666815 TI - [Spatial analysis of domestic violence against women from 2002 to 2005 in Joao Pessoa, Paraiba State, Brazil]. AB - This was a quantitative, ecological, exploratory study using spatial analysis and a geographic information system. The population consisted of all the women that had filed complaints against domestic violence in the city of Joao Pessoa, Paraiba State, Brazil, from 2002 to 2005, at the Specialized Police Precinct for Women. The aim was to investigate the spatial distribution of domestic violence in order to assist policymakers in the decision-making process. Analysis of the results allowed identifying areas of low and high incidence of domestic violence, besides comparing the risk in each neighborhood to the overall rate for the city of Joao Pessoa. Based on the Getis and Ord index, the study produced a decision on priority areas for intervening in domestic violence. The authors highlight the need for changes in care for female victims of violence and the link among institutions with permanent education in the services, including discussions on gender and violence against women. PMID- 22666816 TI - [Aspirin use in cardiovascular disease prevention: a population-based study]. AB - The objective of this study was to estimate the prevalence of aspirin use in primary and secondary prevention of cardiovascular disease. A population-based cross-sectional study was conducted in Pelotas, Rio Grande do Sul State, Brazil, from January to May 2010. The study had two outcomes: 1) aspirin use in primary prevention (individuals > 40 years of age with at least two risk factors: hypertension, diabetes mellitus, and/or hyperlipidemia) and 2) aspirin use in secondary prevention (history of stroke and/or angina/myocardial infarction). The outcomes were analyzed based on demographic, socioeconomic, and lifestyle variables. Prevalence of aspirin use was 24.8% for primary prevention and 34.3% for secondary prevention. In primary prevention, aspirin use was more common in non-whites and older individuals and among those with worse self-rated health. For secondary prevention, aspirin use was more frequent among older and higher income individuals and former smokers. Prevalence of aspirin use was well below recommended levels for prevention of cardiovascular diseases. PMID- 22666817 TI - [Factors associated with adequate fruit and vegetable intake by schoolchildren in Santa Catarina State, Brazil]. AB - This study aimed to estimate fruit and vegetable intake and identify associated factors among schoolchildren in Santa Catarina State, Brazil. A cross-sectional study was conducted with 4,964 students from public and private schools in eight districts in the State, analyzing socioeconomic and anthropometric data and dietary intake. Adequate fruit and vegetable intake was defined as five or more servings per day. Poisson regression was performed to test associations between fruit and vegetable intake and independent variables (p < 0.05). Adequate intake was found in 2.7% of children, while 26.6% of the sample did not consume any fruits and vegetables. In the analysis of the association between independent variables and adequate fruit and vegetable intake in the total sample, only geographic region (residents in western Santa Catarina) and consumption of candy were significantly associated. In the stratified analysis by sex, for boys, only geographic region was associated, while among girls, region and candy consumption were significantly associated with adequate fruit and vegetable intake. The findings indicate the need for specific strategies in the school community to improve fruit and vegetable intake by schoolchildren. PMID- 22666818 TI - [Epidemiological aspects of leprosy: a spatial approach]. AB - The objective of this study was to identify spatial patterns in the occurrence of leprosy in Duque de Caxias, a municipality (county) with high endemicity for the disease in the State of Rio de Janeiro, Brazil. The authors selected all new leprosy cases reported to the Brazilian National Database on Diseases of Notification (SINAN) from 1998 to 2006. The analysis was performed according to three-year periods, followed by spatial analysis according to the local empirical Bayesian method and calculation of global (Moran) and local (LISA) spatial autocorrelation. The analysis showed marked improvement in the epidemiological situation associated with earlier diagnosis. There was a reduction in the proportion of cases with grade II leprosy, from 13.6% to 8.6% (p = 0.04), and increased detection of cases with the indeterminate form, from 10.3% to 18% (p = 0.00). Spatial analysis identified a cluster in the South-Northwest of the municipality, not directly related to the actions or decentralization campaign, proving to be an important tool for identifying critical areas for the endemic and assessing the impact of strategic measures to combat the disease. PMID- 22666819 TI - [Prevalence of uterine cervical cancer testing in Rio Branco, Acre State, Brazil, and factors associated with non-participation in screening]. AB - The objective of the study was to determine the self-reported prevalence of uterine cervical cancer testing in Rio Branco, Acre State, Brazil, and to analyze factors associated with non-participation in screening. A population-based cross sectional study with a sample of 772 women 18 to 69 years of age and living in Rio Branco was conducted in 2007 and 2008. Data were analyzed with Stata 10.0, and prevalence rates were estimated with Poisson multivariate regression (95%CI). 85.3% of women reported at least one cervical cancer screening test in the previous three years. The majority of women (72.8%) were screened in the Brazilian Unified National Health System. After adjusting for selected variables, statistically significant prevalence rates for absence of screening were found in women 18-24 and 60-69 years of age, single, and with low income and low schooling. The prevalence rates were consistent with findings from other studies, highlighting the need for greater intervention in the group of women most vulnerable to cervical cancer incidence and mortality. PMID- 22666820 TI - [Psychological well-being of young people 18 to 24 years of age and associated factors]. AB - This study aimed to identify factors associated with psychological well-being among young people 18 to 24 years of age in Pelotas, Rio Grande do Sul State, Brazil. In a population-based cross-sectional study, 1,621 subjects answered a structured questionnaire on socio-demographic data, religion, employment, and substance use, as well as the Mini International Neuropsychiatric Interview (MINI) to assess psychiatric disorders. The Faces Scale (Andrews) was used to evaluate psychological well-being. Poisson regression was used for multivariate analysis. Of the total sample, 85.3% displayed psychological well-being, which was positively associated with non-use of illicit drugs, current employment, religion, socioeconomic status (classes A and B), higher educational levels, and absence of psychiatric disorders. Programs to reduce poverty and encourage education and identification and prevention of drug use among youths are of paramount importance to improve their health and psychological well-being. PMID- 22666821 TI - [Overweight in children and adolescents in Pernambuco State, Brazil: prevalence and determinants]. AB - This study aimed to determine the prevalence of overweight and associated risk factors in children and adolescents in Pernambuco State, Brazil, in 2006. The cross-sectional, population-based study included 1,435 individuals from 5 to 19 years of age. Poisson regression was used to evaluate the association between selected variables and overweight. Prevalence was 13.3% for overweight (95%CI: 11.6-15.1) and 3.8% for obesity. Adjusted prevalence ratios showed that higher family income, maternal schooling, possession of household consumer goods, living in urban areas, and maternal overweight were associated with overweight in children and adolescents. The high prevalence of overweight in Pernambuco emphasizes the need for public health measures targeting all families regardless of socioeconomic status. PMID- 22666822 TI - Family context and incidence of dental caries in preschool children living in areas covered by the Family Health Strategy in Salvador, Bahia State, Brazil. AB - Psychosocial factors influence family care and can jeopardize child development. This study aimed to analyze the association between maternal common mental disorders and incidence of early dental caries in preschool-age children living in areas covered by the Family Health Strategy in Salvador, Bahia State, Brazil, in a cohort design. A total of 472 children were examined and their mothers were interviewed from 2007 to 2008. Incidence of at least one tooth with caries was 21.19%, while 7.84% of the children showed high risk of caries. The results after adjusting for the child's age and maternal schooling showed that maternal common mental disorders were associated with high caries risk in deciduous teeth (adjusted RR = 2.41, 95%CI: 1.05-5.56, among children with 6 or fewer home appliances in the household; adjusted RR = 3.44, 95%CI: 1.06-11.17, among those that brushed twice or less per day). Maternal mental problems were associated with the development of caries in preschoolers. PMID- 22666823 TI - [Secrets and silences: unspoken aspects of conjugal life for HIV/AIDS serodiscordant couples]. AB - One of the current issues raised by HIV/AIDS is the phenomenon of serodiscordance: affective-sexual relations between partners with different HIV serology. The article analyzes issues that cannot be discussed within established relationships in these couples and/or with family, friends, and neighborhood networks. The article discusses two dimensions of silences and secrets in serodiscordant relationships: (1) individual secrets and silences that are established for each member of the couple and (2) double secrets, established by the couple in relation to others. The article is based on in-depth interviews with 26 serodiscordant couples. The analysis was based on comparative systematization, which allowed observing how the same thematic contents varied according to the interviewee's gender and HIV status. The data show how the subjects develop daily strategies to maintain aspects of private life that can be threatened by the dynamics of gossip, understood not as an independent phenomenon, but as a function of collective norms and beliefs in given social spaces. PMID- 22666824 TI - [Translation and adaptation of the Motorcycle Rider Behavior Questionnaire: a Brazilian version]. AB - Traffic accidents are a leading cause of death in young adults. In Brazil, traffic accidents are proportionally more prevalent among motorcyclists as compared to automobile drivers. Although numerous data indicate that individual characteristics are involved in traffic accident risk, there is no instrument in Brazil to assess motorcyclists' traffic behavior. The authors thus proposed to perform translation and cultural adaptation of the Motorcycle Rider Behavior Questionnaire (MRBQ) into Brazilian Portuguese. The translation process consisted of: two independent translations into Brazilian Portuguese; unification of the translations; back-translation into English; formal assessment of semantic equivalence; application of a summary version in a convenience sample of motorcyclists; generation of a final version; and back-translation and submission to the original author, who approved this version. The Brazilian version maintained its semantic equivalence and was accepted by the convenience sample, an important characteristic for a self-completed instrument. Further studies are necessary to evaluate the questionnaire's psychometric properties in the Brazilian cultural context. PMID- 22666825 TI - An argument for explicit rationing of health resources within the public-private mix in Brazil. PMID- 22666827 TI - Bacteriology of deep carious lesions underneath amalgam restorations with different pulp-capping materials--an in vivo analysis. AB - Microorganisms remaining in dentin following cavity preparation may induce pulp damage, requiring the use of pulp-capping agents with antimicrobial activity underneath permanent restorations. OBJECTIVE: The aims of this study were to analyze the bacteriological status of carious dentin and to assess the efficacy of different base underneath silver amalgam restorations. MATERIAL AND METHODS: This study was conducted on 50 patients aged 13 to 30 years. Sterile swabs were used to take samples after cavity preparation, which was assessed by microbiological culture to identify the microorganisms present. Following this, cavities were restored with silver amalgam, using one of the materials being investigated, as the base: calcium hydroxide (Group II), polyantibiotic paste (Group III), a novel light-cured fluoride-releasing hydroxyapatite-based liner (Group IV) and mineral trioxide aggregate--MTA (Group V). In Group I, the cavities were restored with silver amalgam, without any base. After 3 months, the amalgam was removed and samples taken again and analyzed for the microbial flora. RESULTS: Lactobacilli were the most commonly isolated microorganisms in the samples of carious dentin. Groups IV and V showed negative culture in the 3-month samples. There was no statistically significant difference between Groups I, II and III. There was no significant difference between Groups IV and V (p>0.05). Both Groups IV and V showed significantly better results when compared to Groups I, II and III (p<0.05). CONCLUSIONS: The hydroxyapatite-based liner and MTA performed significantly better in terms of antibacterial activity than the other materials. PMID- 22666826 TI - Modulation of host cell signaling pathways as a therapeutic approach in periodontal disease. AB - Recently, new treatment approaches have been developed to target the host component of periodontal disease. This review aims at providing updated information on host-modulating therapies, focusing on treatment strategies for inhibiting signal transduction pathways involved in inflammation. Pharmacological inhibitors of MAPK, NFkappaB and JAK/STAT pathways are being developed to manage rheumatoid arthritis, periodontal disease and other inflammatory diseases. Through these agents, inflammatory mediators can be inhibited at cell signaling level, interfering on transcription factors activation and inflammatory gene expression. Although these drugs offer great potential to modulate host response, their main limitations are lack of specificity and developments of side effects. After overcoming these limitations, adjunctive host modulating drugs will provide new therapeutic strategies for periodontal treatment. PMID- 22666828 TI - Xylitol concentrations in artificial saliva after application of different xylitol dental varnishes. AB - OBJECTIVE: The present study analyzed xylitol concentrations in artificial saliva over time after application of varnishes containing 10% and 20% xylitol. MATERIAL AND METHODS: Fifteen bovine enamel specimens (8x4 mm) were randomly allocated to 3 groups (n=5/group), according to the type of varnish used: 10% xylitol, 20% xylitol and no xylitol (control). After varnish application (4 mg), specimens were immersed in vials containing 500 uL of artificial saliva. Saliva samples were collected in different times (1, 8, 12, 16, 24, 48 and 72 h) and xylitol concentrations were analyzed. Data were assessed by two-way repeated-measures ANOVA (p<0.05). RESULTS: Colorimetric analysis was not able to detect xylitol in saliva samples of the control group. Salivary xylitol concentrations were significantly higher up to 8 h after application of the 20% xylitol varnish. Thereafter, the 10% xylitol varnish released larger amounts of that polyol in artificial saliva. CONCLUSIONS: Despite the results in short-term, sustained xylitol releases could be obtained when the 10% xylitol varnish was used. These varnishes seem to be viable alternatives to increase salivary xylitol levels, and therefore, should be clinically tested to confirm their effectiveness. PMID- 22666829 TI - Clinical strategies for esthetic excellence in anterior tooth restorations: understanding color and composite resin selection. AB - Direct composite resin restorations have become a viable alternative for patients that require anterior restorative procedures to be integrated to the other teeth that compose the smile, especially for presenting satisfactory esthetic results and minimum wear of the dental structure. Technological evolution along with a better understanding of the behavior of dental tissues to light incidence has allowed the development of new composite resins with better mechanical and optical properties, making possible a more artistic approach for anterior restorations. The combination of the increasing demand of patients for esthetics and the capacity to preserve the dental structure resulted in the development of different incremental techniques for restoring fractured anterior teeth in a natural way. In order to achieve esthetic excellence, dentists should understand and apply artistic and scientific principles when choosing color of restorative materials, as well as during the insertion of the composite resin. The discussion of these strategies will be divided into two papers. In this paper, the criteria for color and material selection to obtain a natural reproduction of the lost dental structures and an imperceptible restoration will be addressed. PMID- 22666830 TI - Clinical diagnosis of hyposalivation in hospitalized patients. AB - OBJECTIVE: The aim of this study was to evaluate the effectiveness of clinical criteria for the diagnosis of hyposalivation in hospitalized patients. MATERIAL AND METHODS: A clinical study was carried out on 145 subjects (48 males; 97 females; aged 20 to 90 years). Each subject was clinically examined, in the morning and in the afternoon, along 1 day. A focused anamnesis allowed identifying symptoms of hyposalivation, like xerostomia complaints (considered as a reference symptom), chewing difficulty, dysphagia and increased frequency of liquid intake. Afterwards, dryness of the mucosa of the cheeks and floor of the mouth, as well as salivary secretion during parotid gland stimulation were assessed during oral examination. RESULTS: Results obtained with Chi-square tests showed that 71 patients (48.9%) presented xerostomia complaints, with a significant correlation with all hyposalivation symptoms (p <0.05). Furthermore, xerostomia was also significantly correlated with all data obtained during oral examination in both periods of evaluation (p<0.05). CONCLUSION: Clinical diagnosis of hyposalivation in hospitalized patients is feasible and can provide an immediate and appropriate therapy avoiding further problems and improving their quality of life. PMID- 22666831 TI - Platelet-rich plasma in the treatment of Class II furcation defects: a histometrical study in dogs. AB - OBJECTIVE: This study was designed to evaluate the potential adjunctive benefits of platelet-rich plasma (PRP) when used with guided-tissue regeneration (GTR) and bioactive glass (BG) in the treatment of Class II furcation lesions. MATERIAL AND METHODS: Bilateral Class II furcation lesions were surgically created and allowed to become chronic in the mandibular third premolars of 9 dogs. The defects were randomly assigned to: A) GTR+BG and B) GTR+BG+PRP. Similar defects were created in the maxillary third premolars and received the same treatments after 45 days. Dogs were sacrificed 90 days after the first treatment. The histometric parameters evaluated were: connective tissue adaptation, new cementum, new bone, mineralized bone area, non-mineralized bone area, and residual BG particle area. RESULTS: Data analysis showed a superior length of new cementum and a greater mineralized bone area for group B in both periods (p<0.05). The non-mineralized bone area was greater in the control group (p<0.05) in both periods. CONCLUSION: Within the limits of this study, it can be concluded that the use of PRP in the treatment of Class II furcation defects may enhance the amount of new cementum and provide a more mineralized bone in a shorter period of time. PMID- 22666832 TI - Influence of tinnitus on pain severity and quality of life in patients with temporomandibular disorders. AB - OBJECTIVE: The aim of this cross-sectional study was to evaluate the relationship among pain intensity and duration, presence of tinnitus and quality of life in patients with chronic temporomandibular disorders (TMD). MATERIAL AND METHODS: Fifty-nine female patients presenting with chronic TMD were selected from those seeking for treatment at the Bauru School of Dentistry Orofacial Pain Center. Patients were submitted to the Research Diagnostic Criteria anamnesis and physical examination. Visual analog scale was used to evaluate the pain intensity while pain duration was assessed by interview. Oral Health Impact Profile inventory modified for patients with orofacial pain was used to evaluate the patients' quality of life. The presence of tinnitus was assessed by self report. The patients were divided into: with or without self report of tinnitus. The data were analyzed statistically using the Student's t-test and Pearson's Chi-square test, with a level of significance of 5%. RESULTS: The mean age for the sample was 35.25 years, without statistically significant difference between groups. Thirty-two patients (54.24%) reported the presence of tinnitus. The mean pain intensity by visual analog scale was 77.10 and 73.74 for the groups with and without tinnitus, respectively. The mean pain duration was 76.12 months and 65.11 months for the groups with and without tinnitus, respectively. The mean OHIP score was 11.72 and 11.74 for the groups with and without tinnitus, respectively. There was no statistically significant difference between groups for pain intensity, pain duration and OHIP scoreS (p>0.05). CONCLUSION: Chronic TMD pain seems to play a more significant role in patient 's quality of life than the presence of tinnitus. PMID- 22666833 TI - A randomized double-blind clinical trial of posterior composite restorations with or without bevel: 1-year follow-up. AB - OBJECTIVE: This randomized double-blind clinical trial compared the performance of posterior composite restorations with or without bevel, after 1-year follow up. MATERIAL AND METHODS: Thirteen volunteers requiring at least two posterior composite restorations were selected. Twenty-nine cavities were performed, comprising 14 without bevel (butt joint) and 15 with bevel preparation of the enamel cavosurface angle. All cavities were restored with simplified adhesive system (Adper Single Bond) and composite resin (Filtek P60). A halogen light curing unit was used through the study. Restorations were polished immediately. Analysis was carried out at baseline, after 6 months and after 1 year by a calibrated evaluator (Kappa), according to the FDI criteria. Data were statistically analyzed by Mann-Whitney test (p <0.05). RESULTS: Beveled and non beveled cavities performed similarly after 1 year follow-up, regarding to fractures and retention, marginal adaptation, postoperative hypersensitivity, recurrence of caries, surface luster and anatomic form. However, for surface and marginal staining, beveled cavities showed significantly better performance (p<0.05) than butt joint restorations. CONCLUSIONS: It was concluded that the restorations were acceptable after 1 year, but restorations placed in cavities with marginal beveling showed less marginal staining than those placed in non beveled cavities. PMID- 22666834 TI - Differential expression of salivary glycoproteins in aggressive and chronic periodontitis. AB - OBJECTIVES: The aim of this study was to compare the pattern of secretion and the expression of mucin glycoprotein-2 (MG2) and lactoferrin in individuals with or without periodontitis. MATERIAL AND METHODS: Five individuals with aggressive periodontitis (APG), 5 with generalized chronic periodontitis (CPG) and 5 without periodontitis (CG) were enrolled after informed consent. Non-stimulated and stimulated submandibular and sublingual saliva was collected and samples analyzed by Western blot probed with specific antibodies. RESULTS: Stimulated and non stimulated salivary flow rates did not differ among groups. Western blot analysis revealed that stimulation led to: an increase in MG2 expression in all groups, and to lactoferrin expression in APG and CPG. In non-stimulated saliva, CG exhibited the highest expression of both glycoproteins. In stimulated saliva, CG exhibited the highest expression of MG2, whereas APG the highest of lactoferrin. CONCLUSIONS: The pattern of secretion of MG2 and lactoferrin in health and disease is complex. Although the present study analyzed samples from a limited number of participants, the reduced expression of MG2 and lactoferrin in APG and CPG under non-stimulated condition, the predominant circumstance of salivary secretion during the day, suggests that these salivary constituents may play a role in the etiopathogenesis of these diseases. PMID- 22666835 TI - Effectiveness of different carbamide peroxide concentrations used for tooth bleaching: an in vitro study. AB - OBJECTIVES: This in vitro study evaluated the effectiveness of three carbamide peroxide concentrations used for tooth bleaching treatments. MATERIAL AND METHODS: Sixty bovine dental slabs (6x6x3 mm) were obtained, sequentially polished, submitted to artificial staining (baseline) and randomized into four groups (n=15), according to the bleaching agent concentration: distilled water (control), 10% (CP10), 16% (CP16) or 37% (CP37) carbamide peroxide. CP10 and CP16 were covered with 0.2 mL of the respective bleaching gels, which were applied on enamel surface for 4 h/day during two weeks. Samples of CP37 were covered with 0.2 mL of the bleaching gel for 20 min. The gel was light activated by two 40-s applications spaced by 10-min intervals. The gel was renewed and applied 3 times per clinical session. This cycle was repeated at 3 sessions with 5 days of interval between them. Tooth shade evaluations were done with a digital spectrophotometer at T0 (baseline), T1 (after 1-week of treatment) and T2 (1-week post-bleaching). Tooth shade means were statistically analyzed by Kruskal-Wallis and Friedman's tests and color parameters were analyzed by two-way ANOVA and Tukey's test (p<0.05). RESULTS: At T1 and T2 evaluations, tooth shade was significantly lighter than at baseline for all treatment groups, considering the color parameters DeltaL*, Deltaa*, Deltab*, DeltaE* (p<0.001) or tooth shade means (p<0.001). CP37 group showed lower shade mean change than CP10 and CP16 at T1 (p<0.01), but this difference was not statistically significant at T2 (p>0.05). CONCLUSIONS: One week after the end of the treatment, all carbamide peroxide concentrations tested produced similar tooth color improvement. PMID- 22666836 TI - Two-year clinical evaluation of three adhesive systems in non-carious cervical lesions. AB - OBJECTIVES: Adhesive systems are continuously being introduced to Dentistry, unfortunately often without sufficient clinical validation. The aim of this study was to evaluate the clinical performance of cervical restorations done with three different adhesive systems. MATERIAL AND METHODS: 158 non-carious cervical lesions of 23 patients were restored with a nanofilled composite resin (Filtek Supreme, 3M/ESPE) combined with Single Bond (3M/ESPE, group SI), Clearfil SE (Kuraray Medical Inc., group CL) and Xeno III (De Trey Dentsply, group XE). In groups SI-B, CL-B and XE-B, the outer surface of the sclerotic dentin was removed by roughening with a diamond bur before application of the respective adhesive systems. In groups CL-BP and XE-BP, after removal of the outer surface of the sclerotic dentin with the bur, the remaining dentin was etched with 37% phosphoric acid and the self-etch adhesive systems Clearfil SE and Xeno III were applied, respectively. Lesions were evaluated at baseline, and restorations after 3 months, 1 year and 2 years using modified USPHS criteria. RESULTS: After 2 years, no significant difference was found between the retention rates of the groups (p >0.05). Although groups CL and SI showed significantly better marginal adaptation than group XE (p<0.05) at 2 years, no significant difference was found between the marginal adaptation of the groups SI-B, CL-B and XE-B (p>0.05). After 2 years no significant difference was observed among the marginal staining results of all groups (p>0.05). CONCLUSION: Although all adhesive systems showed similar retention rates, Clearfil SE and Single Bond showed better marginal adaptation than Xeno III after 2 years of follow-up. PMID- 22666837 TI - Color stability, surface roughness and microhardness of composites submitted to mouthrinsing action. AB - OBJECTIVE: The purpose of this study was to evaluate the effect of mouth rinse solutions on color stability, surface roughness and microhardness of two composite resins. MATERIAL AND METHODS: Fifty test specimens of each composite (Filtek Z250 and Z350; 3M ESPE) were made using a teflon matrix (12x2 mm). Color, surface roughness and Knoop microhardness baseline measurements of each specimen were made and specimens (n=10) were immersed in 5 mouth rinse solutions: G1: distilled water (control), G2: Plax Classic, G3: Plax alcohol-free; G4: Periogard, and G5: Listerine. Final measurements of color, roughness and microhardness were performed and the results submitted to statistical analysis (2 way ANOVA, Bonferroni's test; p<0.05). RESULTS: The most significant color change was observed for Z250 when immersed in Listerine (p<0.05). Z350 showed greater color change when immersed in Plax alcohol-free (p<0.05), but with no significant difference for Listerine (p>0.05). With regard to roughness, both composites showed significant changes when immersed in Listerine in comparison with Plax alcohol-free (p<0.05). Microhardness of Z350 was shown to be significantly changed when the composite was immersed in Plax alcohol-free (p<0.05). CONCLUSION: Composite changes depended on the material itself rather than the mouth rinse solution used. PMID- 22666838 TI - Interference of partial visual analysis of root filling quality and apical status on retreatment decisions. AB - OBJECTIVE: The presence of periapical radiolucency has been used as a criterion for endodontic treatment failure. However, in addition to the inherent limitations of radiographic examinations, radiographic interpretations are extremely subjective. Thus, this study investigated the effect of partial analysis of root filling quality and periapical status on retreatment decisions by general dentists. MATERIAL AND METHODS: Twelve digitalized periapical radiographs were analyzed by 10 observers. The study was conducted at three time points at 1-week intervals. Radiographs edited with the Adobe Photoshop CS4 software were analyzed at three time points: first, only root filling quality was analyzed; second, only the periapical areas of the teeth under study were visualized; finally, observers analyzed the unedited radiographic image. Spearman's coefficient was used to analyze the correlations between the scores assigned when the periapical area was not visible and when the unedited radiograph was analyzed, as well as between the scores assigned when root fillings where not visible and when the unedited radiograph was analyzed. Sensitivity, specificity, positive and negative predictive values between partial images and unedited radiographs were also used to analyze retreatment decisions. The level of significance was set at 5%. RESULTS: The visualization of the root filling on the unedited radiograph affected the interpretation of the periapical status and the technical quality of the fillings has a greater influence on the general dentist's decision to prescribe endodontic retreatment than the periapical condition. CONCLUSION: In order to make endodontic diagnosis, radiographic interpretation process should not only emphasize technical aspects, but also consider biological factors. PMID- 22666839 TI - Degree of conversion of nanofilled and microhybrid composite resins photo activated by different generations of LEDs. AB - OBJECTIVE: This study aimed at evaluating the degree of conversion (DC) of four composite resins, being one nanofilled and 3 microhybrid resins, photo-activated with second- and third-generation light-emitting diodes (LEDs). MATERIAL AND METHODS: FiltekTM Z350 nanofilled composite resins and Amelogen(r) Plus, Vit-l escenceTM and Opallis microhybrid resins were photo-activated with two second generation LEDs (Radii-cal and Elipar Free LightTM 2) and one third-generation LED (Ultra-Lume LED 5) by continuous light mode, and a quartz halogen-tungsten bulb (QHT, control). After 24 h of storage, the samples were pulverized into fine powder and 5 mg of each material were mixed with 100 mg of potassium bromide (KBr). After homogenization, they were pressed, which resulted in a pellet that was evaluated using an infrared spectromer (Nexus 470, Thermo Nicolet) equipped with TGS detector using diffuse reflectance (32 scans, resolution of 4 cm(-1)) coupled to a computer. The percentage of unreacted carbon-carbon double bonds (% C=C) was determined from the ratio of absorbance intensities of aliphatic C=C (peak at 1637 cm-1) against internal standard before and after curing of the specimen: aromatic C-C (peak at 1610 cm-1). RESULTS: The ANOVA showed a significant effect on the interaction between the light-curing units (LCUs) and the composite resins (p<0.001). The Tukey?s test showed that the nanofilled resin (FiltekTM Z350) and Opallis when photo-activated by the halogen lamp (QTH) had the lowest DC compared with the other microhybrid composite resins. The DC of the nanofilled resin (FiltekTM Z350) was also lower using LEDs. The highest degrees of conversion were obtained using the third-generation LED and one of second generation LEDs (Elipar Free LightTM 2). CONCLUSIONS: The nanofilled resin showed the lowest DC, and the Vit-l-escenceTM microhybrid composite resin showed the highest DC. Among the LCUs, it was not possible to establish an order, even though the second-generation LED Radii-cal provided the lowest DC. PMID- 22666840 TI - Effect of obesity on alveolar bone loss in experimental periodontitis in Wistar rats. AB - Obesity has been linked to higher inflammatory status and periodontal breakdown. OBJECTIVE: The purpose of this study was to investigate the effect of obesity on alveolar bone loss in experimental periodontitis in rats. MATERIAL AND METHODS: Twenty-four female Wistar rats were randomly divided into two groups: obese (n=13), which were fed with "cafeteria diet" (CAF diet--high amounts of sucrose and fat) for 90 days in order to gain weight, and non-obese (n=11) regularly fed rats. Ligature-induced experimental periodontitis was created in all animals. Body weight differed statistically between obese and non-obese groups (277.59 and 223.35 g, respectively) at the moment of the ligature placement. Morphometric registration of alveolar bone loss was carried out after 30 days of ligature placement to determine the effect of obesity on the progression of experimental periodontitis. RESULTS: Intra-group comparisons showed significantly higher alveolar bone loss mean values in maxillary teeth with ligature (P<0.05). Alveolar bone loss [mean (SD), mm] was not statistically different between obese and non-obese groups [0.71 (0.09) and 0.65 (0.07) mm, respectively]. However, when palatal sides are analyzed separately, obese group presented significantly higher alveolar bone loss (P<0.05) as compared to non-obese [0.68 (0.12) and 0.53 (0.13) mm, respectively]. CONCLUSIONS: In spite of the weak differences, it is possible to conclude that the progression of alveolar bone loss in ligature induced periodontitis can be potentially influenced by body weight in rats. PMID- 22666841 TI - Alveolar bone healing process in spontaneously hypertensive rats (SHR). A radiographic densitometry study. AB - Hypertension is one of the most important public health problems worldwide. If undiagnosed or untreated, this pathology represents a systemic risk factor and offers unfavorable conditions for dental treatments, especially those requiring bone healing. OBJECTIVES: The purpose of this study was to demonstrate, by analysis of bone mineral density (BMD), that the alveolar bone healing process is altered in spontaneously hypertensive rats (SHRs). MATERIAL AND METHODS: Wistar rats and SHRs were submitted to extraction of the upper right incisor and were euthanized 7, 14, 21, 28 and 42 days after surgery. Right maxillae were collected, radiographed and analyzed using Digora software. BMD was expressed as minimum (min), middle (med) and maximum (max) in the medium (MT) and apical (AT) thirds of the dental alveolus. RESULTS: The results were compared across days and groups. Wistar showed difference in med and max BMD in the MT between 7 and 28 and also between 14 and 28 days. The AT exhibited significant difference in med and min BMD between 7 and 28 days, as well as difference in min BMD between 28 and 42 days. SHRs showed lower med BMD in the MT at 28 days when compared to 21 and 42 days. Differences were observed across groups in med and min BMD at day 28 in the MT and AT; and in max BMD at 14, 21 and 42 days in the MT. CONCLUSIONS: These results suggest that the alveolar bone healing process is delayed in SHRs comparing with Wistar rats. PMID- 22666842 TI - Clinical evaluation of the failure rates of metallic brackets. AB - OBJECTIVES: The aim of this study was to evaluate in vivo the bonding of metallic orthodontic brackets with different adhesive systems. MATERIAL AND METHODS: Twenty patients (10.5-15.1 years old) who had sought corrective orthodontic treatment at a University Orthodontic Clinic were evaluated. Brackets were bonded from the right second premolar to the left second premolar in the upper and lower arches using: Orthodontic Concise, conventional Transbond XT, Transbond XT without primer, and Transbond XT associated with Transbond Plus Self-etching Primer (TPSEP). The 4 adhesive systems were used in all patients using a split mouth design; each adhesive system was used in one quadrant of each dental arch, so that each group of 5 patients received the same bonding sequence. Initial archwires were inserted 1 week after bracket bonding. The number of bracket failures for each adhesive system was quantified over a 6-month period. RESULTS: The number of debonded brackets was: 8--Orthodontic Concise, 2--conventional Transbond XT, 9--Transbond XT without primer, and 1--Transbond XT + TPSEP. By using the Kaplan-Meier methods, statistically significant differences were found between the materials (p=0.0198), and the Logrank test identified these differences. Conventional Transbond XT and Transbond XT + TPSEP adhesive systems were statistically superior to Orthodontic Concise and Transbond XT without primer (p<0.05). There was no statistically significant difference between the dental arches (upper and lower), between the dental arch sides (right and left), and among the quadrants. CONCLUSIONS: The largest number of bracket failures occurred with Orthodontic Concise and Transbond XT without primer systems and few bracket failures occurred with conventional Transbond XT and Transbond XT+TPSEP. More bracket failures were observed in the posterior region compared with the anterior region. PMID- 22666843 TI - Internal fit of two all-ceramic systems and metal-ceramic crowns. AB - OBJECTIVES: The aim of this study was to investigate the internal fit (IF) of glass-infiltrated alumina (ICA--In-Ceram Alumina), yttria-stabilized tetragonal zirconia polycrystals (Y-TZP--IPS e.max ZirCAD), and metal-ceramic (MC--Ni-Cr alloy) crowns. MATERIAL AND METHODS: Sixty standardized resin-tooth replicas of a maxillary first molar were produced for crown placement and divided into 3 groups (n=20 each) according to the core material used (metal, ICA or Y-TZP). The IF of the crowns was measured using the replica technique, which employs a light body polyvinyl siloxane impression material to simulate the cement layer thickness. The data were analyzed according to the surfaces obtained for the occlusal space (OS), axial space (AS) and total mean (TM) using two-way ANOVA with Tukey's multiple comparison test (p<0.05). RESULTS: No differences among the different areas were detected in the MC group. For the Y-TZP and ICA groups, AS was statistically lower than both OS and TM. No differences in AS were observed among the groups. However, OS and TM showed significantly higher values for ICA and Y TZP groups than MC group. Comparisons of ICA and Y-TZP revealed that OS was significantly lower for Y-TZP group, whereas no differences were observed for TM. CONCLUSIONS: The total mean achieved by all groups was within the range of clinical acceptability. However, the metal-ceramic group demonstrated significantly lower values than the all-ceramic groups, especially in OS. PMID- 22666844 TI - Assessment and management of oral health in liver transplant candidates. AB - Liver transplantation has become a standard treatment for end-stage liver disease and the number of recipients has grown rapidly in the last few years. Dental care during pre-transplant workup is important to reduce potential sources of infection in the drug-induced immunosuppression phase of liver transplantation. OBJECTIVES: The objectives of this study were to document the prevalence of oral abnormalities in patients on a liver transplant waiting list presenting to an urban dental school clinic, discuss the appropriate dental treatment according their systemic conditions and compare their oral manifestations with those of healthy individuals. MATERIAL AND METHODS: A pilot study was conducted involving 16 end-stage liver disease individuals (study group- SG) attending the Special Care Dentistry Center of the University of Sao Paulo and 16 control individuals (control group--CG) with no liver diseases, receiving dental care at the Dental School of the University of Sao Paulo. These individuals were assessed for their dental status (presence of oral disease or abnormalities), coagulation status, and dental treatment indications. RESULTS: The patients from SG exhibited a greater incidence of oral manifestations compared with CG (p=0.0327) and were diagnosed with at least one oral disease or condition that required treatment. Coagulation abnormalities reflecting an increased risk of bleeding were found in 93.75% of the patients. However, no bleeding complications occurred after dental treatment. CONCLUSIONS: The patients with chronic liver diseases evaluated in this study exhibited a higher incidence of oral manifestations compared with the control group and had at least one oral disease or abnormality which required dental treatment prior to liver transplantation. Careful oral examination and evaluation of the patient, including laboratory tests, will ensure correct oral preparation and control of oral disease prior to liver transplantation. PMID- 22666845 TI - Effect of light sources and curing mode techniques on sorption, solubility and biaxial flexural strength of a composite resin. AB - Adequate polymerization plays an important role on the longevity of the composite resin restorations. OBJECTIVES: The aim of this study was to evaluate the effect of light-curing units, curing mode techniques and storage media on sorption, solubility and biaxial flexural strength (BFS) of a composite resin. MATERIAL AND METHODS: Two hundred and forty specimens were made of one composite resin (Esthet X) in a stainless steel mold (2 mm x 8 mm O), and divided into 24 groups (n=10) established according to the 4 study factors: light-curing units: quartz tungsten halogen (QTH) lamp and light-emitting diodes (LED); energy densities: 16 J/cm2 and 20 J/cm2; curing modes: conventional (CM) and pulse-delay (PD); and permeants: deionized water and 75% ethanol for 28 days. Sorption and solubility tests were performed according to ISO 4049:2000 specifications. All specimens were then tested for BFS according to ASTM F394-78 specification. Data were analyzed by three-way ANOVA followed by Tukey, Kruskal-Wallis and Mann-Whitney tests (alpha=0.05). RESULTS: In general, no significant differences were found regarding sorption, solubility or BFS means for the light-curing units and curing modes (p>0.05). Only LED unit using 16 J/cm2 and PD using 10 s produced higher sorption and solubility values than QTH. Otherwise, using CM (16 J/cm2), LED produced lower values of BFS than QTH (p<0.05). 75% ethanol permeant produced higher values of sorption and solubility and lower values of BFS than water (p<0.05). CONCLUSION: Ethanol storage media produced more damage on composite resin than water. In general the LED and QTH curing units using 16 and 20 J/cm2 by CM and PD curing modes produced no influence on the sorption, solubility or BFS of the tested resin. PMID- 22666846 TI - Influence of combined oral contraceptives on the periodontal condition. AB - Most studies investigating the impact of oral contraceptives have been performed some years ago, when the level of sexual hormones was greater than the actual formulations. OBJECTIVE: The aim of this study was to evaluate the effects of current combined oral contraceptives (COC) on periodontal tissues, correlating the clinical parameters examined with the total duration of continuous oral contraceptive intake. MATERIAL AND METHODS: Twenty-five women (19-35 years old) taking combined oral contraceptives for at least 1 year were included in the test group. The control group was composed by 25 patients at the same age range reporting no use of hormone-based contraceptive methods. Clinical parameters investigated included pocket probing depth (PD), clinical attachment level (CAL), sulcular bleeding index (SBI) and plaque index (Pl.I). Data were statistically evaluated by unpaired t test, Pearson's correlation test and Spearman's correlation test. RESULTS: The test group showed increased PD (2.228+/-0.011 x 2.154+/-0.012; p<0.0001) and SBI (0.229+/-0.006 x 0.148+/-0.005, p<0.0001) than controls. No significant differences between groups were found in CAL (0.435+/ 0.01 x 0.412+/-0.01; p=0.11). The control group showed greater Pl.I than the test group (0.206+/-0.007 x 0.303+/-0.008; p<0.0001). No correlation between the duration of oral contraceptive intake, age and periodontal parameters was observed. CONCLUSIONS: These findings suggest that the use of currently available combined oral contraceptives can influence the periodontal conditions of the patients, independently of the level of plaque accumulation or total duration of medication intake, resulting in increased gingival inflammation. PMID- 22666847 TI - Effect of root canal filling materials on dimensions of cone-beam computed tomography images. AB - OBJECTIVE: To evaluate the discrepancy of root canal filling (RCF) measurements obtained from original root specimens and cone-beam computed tomography (CBCT) images. MATERIAL AND METHODS: Seventy-two human maxillary anterior teeth were prepared up to an ISO #50 K-File 1 mm short of the apical foramen. Thus, the teeth were randomly divided into 8 groups, according to the root canal filling material: Sealapex(r), Sealapex(r)+gutta-percha points, Sealer 26(r), Sealer 26(r)+gutta-percha points, AH PlusTM, AH PlusTM+gutta-percha points, Grossman Sealer, and Grossman Sealer+gutta-percha points. After root canal preparation and RCF, CBCT scans were acquired and the specimens were sectioned in axial, sagittal and coronal planes. The RCF measurements were obtained in different planes and thicknesses to determine the discrepancy between the original root specimens (using a digital caliper) and the CBCT images (using the scanner's proprietary software). One-way analysis of variance and Tukey tests were used for statistical analyses. The significance level was set at alpha=5%. RESULTS: Measurements of the different endodontic filling materials were 9% to 100% greater on the CBCT images than on the original root specimens. Greater RCF dimensions were found when only sealers were used, with statistically significant difference among the groups. CONCLUSIONS: RCF dimensions were greater on CBCT images than on the original root specimens, especially when only sealer was used. PMID- 22666848 TI - Surgical management of dentigerous cyst and keratocystic odontogenic tumor in children: a conservative approach and 7-year follow-up. AB - Dentigerous cyst (DC) is one of the most common odontogenic cysts of the jaws and rarely recurs. On the other hand, keratocystic odontogenic tumor (KCOT), formerly known as odontogenic keratocyst (OKC), is considered a benign unicystic or multicystic intraosseous neoplasm and one of the most aggressive odontogenic lesions presenting relatively high recurrence rate and a tendency to invade adjacent tissue. Two cases of these odontogenic lesions occurring in children are presented. They were very similar in clinical and radiographic characteristics, and both were treated by marsupialization. The treatment was chosen in order to preserve the associated permanent teeth with complementary orthodontic treatment to direct eruption of the associated permanent teeth. At 7-years of follow-up, none of the cases showed recurrence. PMID- 22666850 TI - Posterior crossbite--treatment and stability. AB - Posterior crossbite is defined as an inadequate transversal relationship of maxillary and mandibular teeth. Even when eliminating the etiologic factors, this malocclusion does not have a spontaneous correction, and should be treated with maxillary expansion as early as possible. This treatment aims at providing a better tooth/skeletal relationship, thereby improving masticatory function, and establishing a symmetrical condyle/fossa relationship. Should posterior crossbite not be treated early, it may result in skeletal changes, demanding a more complex approach. Additionally, an overcorrection expansion protocol should be applied in order to improve the treatment stability. Although the literature has reported a high rate of relapse after maxillary expansion, the goal of this study was to demonstrate excellent stability of the posterior crossbite correction 21 years post treatment. PMID- 22666849 TI - Rehabilitative treatment of cleft lip and palate: experience of the Hospital for Rehabilitation of Craniofacial Anomalies-USP (HRAC-USP)--part 2: pediatric dentistry and orthodontics. AB - The aim of this article is to present the pediatric dentistry and orthodontic treatment protocol of rehabilitation of cleft lip and palate patients performed at the Hospital for Rehabilitation of Craniofacial Anomalies-University of Sao Paulo (HRAC-USP). Pediatric dentistry provides oral health information and should be able to follow the child with cleft lip and palate since the first months of life until establishment of the mixed dentition, craniofacial growth and dentition development. Orthodontic intervention starts in the mixed dentition, at 8-9 years of age, for preparing the maxillary arch for secondary bone graft procedure (SBGP). At this stage, rapid maxillary expansion is performed and a fixed palatal retainer is delivered before SBGP. When the permanent dentition is completed, comprehensive orthodontic treatment is initiated aiming tooth alignment and space closure. Maxillary permanent canines are commonly moved mesially in order to substitute absent maxillary lateral incisors. Patients with complete cleft lip and palate and poor midface growth will require orthognatic surgery for reaching adequate anteroposterior interarch relationship and good facial esthetics. PMID- 22666852 TI - The classification of esterases: an important gene family involved in insecticide resistance--a review. AB - The use of chemical insecticides continues to play a major role in the control of disease vector populations, which is leading to the global dissemination of insecticide resistance. A greater capacity to detoxify insecticides, due to an increase in the expression or activity of three major enzyme families, also known as metabolic resistance, is one major resistance mechanisms. The esterase family of enzymes hydrolyse ester bonds, which are present in a wide range of insecticides; therefore, these enzymes may be involved in resistance to the main chemicals employed in control programs. Historically, insecticide resistance has driven research on insect esterases and schemes for their classification. Currently, several different nomenclatures are used to describe the esterases of distinct species and a universal standard classification does not exist. The esterase gene family appears to be rapidly evolving and each insect species has a unique complement of detoxification genes with only a few orthologues across species. The examples listed in this review cover different aspects of their biochemical nature. However, they do not appear to contribute to reliably distinguish among the different resistance mechanisms. Presently, the phylogenetic criterion appears to be the best one for esterase classification. Joint genomic, biochemical and microarray studies will help unravel the classification of this complex gene family. PMID- 22666854 TI - Evolution of insecticide resistance in non-target black flies (Diptera: Simuliidae) from Argentina. AB - Black flies, a non-target species of the insecticides used in fruit production, represent a severe medical and veterinary problem. Large increases in the level of resistance to the pyrethroids fenvalerate (more than 355-fold) and deltamethrin (162-fold) and a small increase in resistance to the organophosphate azinphos methyl (2-fold) were observed between 1996-2008 in black fly larvae under insecticide pressure. Eventually, no change or a slight variation in insecticide resistance was followed by a subsequent increase in resistance. The evolution of pesticide resistance in a field population is a complex and stepwise process that is influenced by several factors, the most significant of which is the insecticide selection pressure, such as the dose and frequency of application. The variation in insecticide susceptibility within a black fly population in the productive area may be related to changes in fruit-pest control. The frequency of individuals with esterase activities higher than the maximum value determined in the susceptible population increased consistently over the sampling period. However, the insecticide resistance was not attributed to glutathione S-transferase activity. In conclusion, esterase activity in black flies from the productive area is one mechanism underlying the high levels of resistance to pyrethroids, which have been recently used infrequently. These enzymes may be reselected by currently used pesticides and enhance the resistance to these insecticides. PMID- 22666853 TI - Primary resistance of HIV to antiretrovirals among individuals recently diagnosed at voluntary counselling and testing centres in the metropolitan region of Recife, Pernambuco. AB - Determining the prevalence and type of antiretroviral (ARV) resistance among ARV naive individuals is important to assess the potential responses of these individuals to first-line regimens. The prevalence of primary resistance and the occurrence of recent infections among individuals with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) were identified among recently diagnosed patients at five sexually transmitted disease/AIDS testing and counselling centres in the metropolitan region of Recife (RMR), Pernambuco, Brazil, between 2007-2009. One-hundred and eight samples were analysed using the Calypte(r) BED assay. Males predominated (56%), as did patients aged 31-50 years. Twenty-three percent presented evidence of a recent HIV infection. The median CD4+ T lymphocyte count was 408 cells/mm3 and the median viral load was 3.683 copies/mL. The prevalence of primary resistance was 4.6% (confidence interval 95% = 1-8.2%) based on criteria that excluded common polymorphisms in accordance with the surveillance drug resistance mutation criteria. The prevalence of resistance to non-nucleoside reverse transcriptase, nucleoside/nucleotide reverse transcriptase and protease inhibitors were 3.8%, 1.5% and 0.8%, respectively. Fifty-seven percent of strains were from clade B, 37.7% were clade F and 3.1% were clade C; there were no statistically significant differences with respect to resistance between clades. Recent infection tended to be more common in men (p = 0.06) and in municipalities in the south of the RMR (Jaboatao dos Guararapes and Cabo de Santo Agostinho) (p = 0.046). The high prevalence of recent infection and the high prevalence of non-B strains in this poor Brazilian region merit further attention. PMID- 22666855 TI - Cryptococcus neoformans carried by Odontomachus bauri ants. AB - Cryptococcus neoformans is the most common causative agent of cryptococcosis worldwide. Although this fungus has been isolated from a variety of organic substrates, several studies suggest that hollow trees constitute an important natural niche for C. neoformans. A previously surveyed hollow of a living pink shower tree (Cassia grandis) positive for C. neoformans in the city of Rio de Janeiro, Brazil, was chosen for further investigation. Odontomachus bauri ants (trap-jaw ants) found inside the hollow were collected for evaluation as possible carriers of Cryptococcus spp. Two out of 10 ants were found to carry phenoloxidase-positive colonies identified as C. neoformans molecular types VNI and VNII. The ants may have acted as a mechanical vector of C. neoformans and possibly contributed to the dispersal of the fungi from one substrate to another. To the best of our knowledge, this is the first report on the association of C. neoformans with ants of the genus Odontomachus. PMID- 22666856 TI - Sandflies (Diptera: Psychodidae) in a focus of visceral leishmaniasis in White Nile, Sudan. AB - Visceral leishmaniasis (VL) has been known to occur since the 1980s on the western bank of the White Nile River (Central Sudan), 150 km south of Khartoum, and has resulted in high mortality. The most recent outbreak of the disease in this area began in 2006. Entomological surveys were carried out during May 2008, June 2010 and May and July 2011 in the White Nile area. Sandflies were collected using Centers for Disease Control light traps and sticky oil traps in the village of Kadaba and the nearby woodland. Phlebotomus females were dissected for the presence of Leishmania promastigotes. A total of 17,387 sandflies, including six species of Phlebotomus and 10 species of Sergentomyia, were identified. The Phlebotomus species recorded were Phlebotomus orientalis, Phlebotomus papatasi, Phlebotomus bergeroti, Phlebotomus duboscqi, Phlebotomus rodhaini and Phlebotomus saevus. P. orientalis was collected in both habitats. The relative abundance of P. orientalis in the woodland habitat was higher than that recorded in the village habitat. In the woodland habitat, there was a notable increase in the relative abundance of P. orientalis during the surveys conducted in 2008 and 2010 compared to 2011. None of the 311 P. orientalis females dissected were infected with Leishmania promastigotes, although relatively high parous rates were recorded in both habitats. Based on the distribution of P. orientalis recorded in this study, this species is the most likely vector of VL in the endemic focus in the White Nile area. Further investigation is required to elucidate the seasonal abundance and distribution of the vector, as well as the transmission season of VL in both habitats so that appropriate control strategies for the vector can be designed. PMID- 22666857 TI - Detection and differentiation of Cryptosporidium by real-time polymerase chain reaction in stool samples from patients in Rio de Janeiro, Brazil. AB - This study reports the first genetic characterisation of Cryptosporidium isolates in Brazil using real-time polymerase chain reaction (RT-PCR). A total of 1,197 faecal specimens from children and 10 specimens from human immunodeficiency virus infected patients were collected between 1999-2010 and screened using microscopy. Forty-eight Cryptosporidium oocyst-positive isolates were identified and analysed using a generic TaqMan assay targeting the 18S rRNA to detect Cryptosporidium species and two other TaqMan assays to identify Cryptosporidium hominis and Cryptosporidium parvum. The 18S rRNA assay detected Cryptosporidium species in all 48 of the stool specimens. The C. parvum TaqMan assay correctly identified five/48 stool samples, while 37/48 stool specimens were correctly amplified in the C. hominis TaqMan assay. The results obtained in this study support previous findings showing that C. hominis infections are more prevalent than C. parvum infections in Brazil and they demonstrate that the TaqMan RT-PCR procedure is a simple, fast and valuable tool for the detection and differentiation of Cryptosporidium species. PMID- 22666858 TI - Natural Leishmania sp. reservoirs and phlebotomine sandfly food source identification in Ibitipoca State Park, Minas Gerais, Brazil. AB - Leishmania spp are distributed throughout the world and different species are associated with varying degrees of disease severity. However, leishmaniasis is thought to be confined to areas of the world where its insect vectors, sandflies, are present. Phlebotomine sandflies obtain blood meals from a variety of wild and domestic animals and sometimes from humans. These vectors transmit Leishmania spp, the aetiological agent of leishmaniasis. Identification of sandfly blood meals has generally been performed using serological methods, although a few studies have used molecular procedures in artificially fed insects. In this study, cytochrome b gene (cytB) polymerase chain reaction (PCR) was performed in DNA samples isolated from 38 engorged Psychodopygus lloydi and the expected 359 bp fragment was identified from all of the samples. The amplified product was digested using restriction enzymes and analysed for restriction fragment length polymorphisms (RFLPs). We identified food sources for 23 females; 34.8% yielded a primate-specific banding profile and 26.1% and 39.1% showed banding patterns specific to birds or mixed restriction profiles (rodent/marsupial, human/bird, rodent/marsupial/human), respectively. The food sources of 15 flies could not be identified. Two female P. lloydi were determined to be infected by Leishmania using internal transcribed spacer 1 and heat shock protein 70 kDa PCR-RFLP. The two female sandflies, both of which fed on rodents/marsupials, were further characterised as infected with Leishmania (Viannia) braziliensis. These results constitute an important step towards applying methodologies based on cytB amplification as a tool for identifying the food sources of female sandflies. PMID- 22666859 TI - Aggregative adherent strains of Corynebacterium pseudodiphtheriticum enter and survive within HEp-2 epithelial cells. AB - Corynebacterium pseudodiphtheriticum is a well-known human pathogen that mainly causes respiratory disease and is associated with high mortality in compromised hosts. Little is known about the virulence factors and pathogenesis of C. pseudodiphtheriticum. In this study, cultured human epithelial (HEp-2) cells were used to analyse the adherence pattern, internalisation and intracellular survival of the ATCC 10700 type strain and two additional clinical isolates. These microorganisms exhibited an aggregative adherence-like pattern to HEp-2 cells characterised by clumps of bacteria with a "stacked-brick" appearance. The differences in the ability of these microorganisms to invade and survive within HEp-2 cells and replicate in the extracellular environment up to 24 h post infection were evaluated. The fluorescent actin staining test demonstrated that actin polymerisation is involved in the internalisation of the C. pseudodiphtheriticum strains. The depolymerisation of microfilaments by cytochalasin E significantly reduced the internalisation of C. pseudodiphtheriticum by HEp-2 cells. Bacterial internalisation and cytoskeletal rearrangement seemed to be partially triggered by the activation of tyrosine kinase activity. Although C. pseudodiphtheriticum strains did not demonstrate an ability to replicate intracellularly, HEp-2 cells were unable to fully clear the pathogen within 24 h. These characteristics may explain how some C. pseudodiphtheriticum strains cause severe infection in human patients. PMID- 22666860 TI - The level of ascorbate peroxidase is enhanced in benznidazole-resistant populations of Trypanosoma cruzi and its expression is modulated by stress generated by hydrogen peroxide. AB - Ascorbate peroxidases (APX) are class I heme-containing enzymes that convert hydrogen peroxide into water molecules. The gene encoding APX has been characterized in 11 strains of Trypanosoma cruzi that are sensitive or resistant to benznidazole (BZ). Bioinformatic analysis revealed the presence of two complete copies of the T. cruzi APX (TcAPX) gene in the genome of the parasite, while karyotype analysis showed that the gene was present in the 2.000-kb chromosome of all of the strains analyzed. The sequence of TcAPX exhibited greater levels of similarity to those of orthologous enzymes from Leishmania spp than to APXs from the higher plant Arabidopsis thaliana. Northern blot and real time reverse transcriptase polymerase chain reaction (RT-PCR) analyses revealed no significant differences in TcAPX mRNA levels between the T. cruzi strains analyzed. On the other hand, Western blots showed that the expression levels of TcAPX protein were, respectively, two and three-fold higher in T. cruzi populations with in vitro induced (17 LER) and in vivo selected (BZR) resistance to BZ, in comparison with their corresponding susceptible counterparts. Moreover, the two BZ-resistant populations exhibited higher tolerances to exogenous hydrogen peroxide than their susceptible counterparts and showed TcAPX levels that increased in a dose-dependent manner following exposure to 100 and 200 uM hydrogen peroxide. PMID- 22666861 TI - Trichinella spiralis shares epitopes with human autoantigens. AB - Like other helminths, Trichinella spiralis has evolved strategies to allow it to survive in the host organism, including the expression of epitopes similar to those present in either expressed or hidden host antigens. To identify T. spiralis-derived antigens that are evolutionarily conserved in the parasite and its host and that could be responsible for its evasion of the host immune response, we examined the reactivity of six different types of autoantibodies to T. spiralis larvae from muscle. T. spiralis antigens that share epitopes with human autoantigens were identified by assessing the cross-reactivity of autoantibody-containing serum samples with T. spiralis antigens in the absence of specific anti-parasite antibodies. Of the 55 autoantibody-containing human serum samples that we analysed by immunohistological screening, 24 (43.6%) recognised T. spiralis muscle larvae structures such as the subcuticular region, the genital primordium or the midgut. Using Western blots, we demonstrated that the same sera reacted with 24 protein components of T. spiralis muscle larvae excretory secretory L1 antigens. We found that the human autoantibodies predominantly bound antigens belonging to the TSL1 group; more specifically, the autoantibody containing sera reacted most frequently with the 53-kDa component. Thus, this protein is a good candidate for further studies of the mechanisms of T. spiralis mediated immunomodulation. PMID- 22666862 TI - Effect of serum sample inactivation on the performance of latex agglutination test for paracoccidioidomycosis serodiagnosis. AB - Paracoccidioidomycosis is diagnosed from the direct observation of the causative agent, but serology can facilitate and decrease the time required for diagnosis. The objective of this study was to determine the influence of serum sample inactivation on the performance of the latex agglutination test (LAT) for detecting antibodies against Paracoccidioides brasiliensis. The sensitivity of LAT from inactivated or non-inactivated samples was 73% and 83%, respectively and the LAT selectivity was 79% and 90%, respectively. The LAT evaluated here was no more specific than the double-immunodiffusion assay. We suggest the investigation of other methods for improving the LAT, such as the use of deglycosylated antigen. PMID- 22666864 TI - Footprints of a trypanosomatid RNA world: pre-small subunit rRNA processing by spliced leader addition trans-splicing. AB - The addition of a capped mini-exon [spliced leader (SL)] through trans-splicing is essential for the maturation of RNA polymerase (pol) II-transcribed polycistronic pre-mRNAs in all members of the Trypanosomatidae family. This process is an inter-molecular splicing reaction that follows the same basic rules of cis-splicing reactions. In this study, we demonstrated that mini-exons were added to precursor ribosomal RNA (pre-rRNA) are transcribed by RNA pol I, including the 5' external transcribed spacer (ETS) region. Additionally, we detected the SL-5'ETS molecule using three distinct methods and located the acceptor site between two known 5'ETS rRNA processing sites (A' and A1) in four different trypanosomatids. Moreover, we detected a polyadenylated 5'ETS upstream of the trans-splicing acceptor site, which also occurs in pre-mRNA trans splicing. After treatment with an indirect trans-splicing inhibitor (sinefungin), we observed SL-5'ETS decay. However, treatment with 5-fluorouracil (a precursor of RNA synthesis that inhibits the degradation of pre-rRNA) led to the accumulation of SL-5'ETS, suggesting that the molecule may play a role in rRNA degradation. The detection of trans-splicing in these molecules may indicate broad RNA-joining properties, regardless of the polymerase used for transcription. PMID- 22666863 TI - Short-term therapy with simvastatin reduces inflammatory mediators and heart inflammation during the acute phase of experimental Chagas disease. AB - Trypanosoma cruzi infection induces progressive cardiac inflammation that leads to fibrosis and modifications in the heart architecture and functionality. Statins, such as 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors, have been studied due to their pleiotropic roles in modulating the inflammatory response. Our goal was to evaluate the effects of simvastatin on the cardiac inflammatory process using a cardiotropic strain of T. cruzi in a murine model of Chagas cardiomyopathy. C57BL/6 mice were infected with 500 trypomastigotes of the Colombian strain of T. cruzi and treated with an oral dose of simvastatin (20 mg/Kg/day) for one month and inflammatory and morphometric parameters were subsequently evaluated in the serum and in the heart, respectively. Simvastatin reduced the total cholesterol and inflammatory mediators (interferon-gamma, tumour necrosis factor-alpha, CCL2 and CCL5) in the serum and in the heart tissue at 30 days post-infection. Additionally, a proportional reduction in heart weight and inflammatory infiltration was observed. Simvastatin also reduced epimastigote proliferation in a dose-dependent manner in vitro and was able to reduce blood trypomastigotes and heart amastigote nests during the acute phase of Chagas disease in vivo. Based on these data, we conclude that simvastatin exerts a modulatory effect on the inflammatory mediators that are elicited by the Colombian strain of T. cruzi and ameliorates the heart damage that is observed in a murine model of Chagas disease. PMID- 22666865 TI - The impact of highly active antiretroviral therapy on the survival of vertically HIV-infected children and adolescents in Belo Horizonte, Brazil. AB - The use of highly active antiretroviral therapy (HAART) for human immunodeficiency virus (HIV)-infected patients has reduced the number of acquired immune deficiency syndrome-related deaths worldwide. This study assessed the impact of HAART on the survival and death rates of vertically HIV-infected children and adolescents in Belo Horizonte, Brazil. Data were obtained from a historic cohort of vertically HIV-infected children and adolescents aged zero-19 years old who were admitted from March 1989-December 2004 and were followed until June 2006. Patients who used HAART were included if they were treated for at least 12 weeks. Of 359 patients, 320 patients met the inclusion criteria. The overall mortality rate was 9.7% [31/320; 95% confidence interval (CI): 6.0-13%]. The median survival for the non-HAART and HAART groups was 31.5 and 55.9 months, respectively (log rank = 22.11, p < 0.0001). In the multivariate analysis, the statistically significant variables were HAART and the weight-for-age Z score < 2, with HAART constituting a protective factor [relative risk (RR): 0.13; CI 95%: 0.05-0.33] and malnutrition constituting a risk factor (RR: 3.44; CI 95%: 1.60 7.40) for death. The incidence of death was 5.1/100 person-years in the non-HAART group and 0.8/100 person-years in the HAART group (p < 0.0001). PMID- 22666866 TI - Syphacia sp. (Nematoda: Oxyuridae) in coprolites of Kerodon rupestris Wied, 1820 (Rodentia: Caviidae) from 5,300 years BP in northeastern Brazil. AB - We present the results of paleoparasitological analyses in coprolites of Kerodon rupestris, rodent endemic to rocky areas of Brazil's semiarid region. The coprolites were collected from excavations at the archaeological site of Toca dos Coqueiros, in the National Park of Serra da Capivara, southeastern of state of Piaui. Syphacia sp. (Nematoda: Oxyuridae) eggs were identified in coprolites dated at 5,300 +/- 50 years before present. This is the first record of the genus Syphacia in rodent coprolites in the Americas. PMID- 22666867 TI - Disruption of the peritrophic matrix by exogenous chitinase feeding reduces fecundity in Lutzomyia longipalpis females. AB - Lutzomyia longipalpis is the most important vector of visceral leishmaniasis in Brazil. When female sandflies feed on blood, a peritrophic matrix (PM) is formed around the blood bolus. The PM is secreted by midgut cells and composed of proteins, glycoproteins and chitin microfibrils. The PM functions as both a physical barrier against pathogens present in the food bolus and blood meal digestion regulator. Previous studies of mosquitoes and sandflies have shown that the absence of a PM, resulting from adding an exogenous chitinase to the blood meal, accelerates digestion. In the present study, we analysed biological factors associated with the presence of a PM in L. longipalpis females. Insects fed blood containing chitinase (BCC) accelerated egg-laying relative to a control group fed blood without chitinase. However, in the BCC-fed insects, the number of females that died without laying eggs was higher and the number of eggs laid per female was lower. The eggs in both groups were viable and generated adults. Based on these data, we suggest that the absence of a PM accelerates nutrient acquisition, which results in premature egg production and oviposition; however, the absence of a PM reduces the total number of eggs laid per female. Reduced fecundity in the absence of a PM may be due to inefficient nutrient conversion or the loss of the protective role of the PM. PMID- 22666869 TI - Identification of the natural breeding sites of sandflies (Diptera: Psychodidae: Phlebotominae), potential vectors of leishmaniasis, in the province of Chaco, Argentina. AB - The aim of this work was to identify the natural breeding sites of sandflies in the province of Chaco, Argentina, for the first time. Preliminary studies were conducted in two different phytogeographic regions: dry Chaco (Parque Provincial Pampa del Indio), in January 2010, and humid Chaco (Resistencia, Margarita Belen and Colonia Benitez), from May-September 2010. A total of 127 samples were collected (Pampa del Indio: 15, Resistencia: 37, Margarita Belen: 36, Colonia Benitez: 39). A female of Migonemyia migonei was found in Pampa del Indio at the base of a bromeliad in the summer (January) and a pupal exuvium of a phlebotomine fly was found in Resistencia, in a place where dogs rested, in the winter (July). These findings highlighted these two sites as potential breeding sites. Because the existence of potential natural breeding sites for sandflies has been demonstrated in both forest and periurban areas, expanding the search efforts and characterising these sites will enable the development of specific study designs to gain insight into the spatial distribution of the risks posed by these vectors. The resulting information will serve as a basis for proposing and evaluating vector control measures. PMID- 22666868 TI - Can Mosquito Magnet(r) substitute for human-landing catches to sample anopheline populations? AB - The efficiency of the Mosquito Magnet Liberty PlusTM (MMLP) trap was evaluated in comparison to human-landing catches (HLCs) to sample anopheline populations in Jabillal, state of Bolivar, southern Venezuela. The village comprised 37 houses and a population of 101; malaria in this village is primarily due to Plasmodium vivax and the Annual Parasite Index is 316.8 per 1,000 population. A longitudinal study was conducted between June 2008-January 2009 for three nights per month every two months between 17:30 pm-21:30 pm, a time when biting mosquitoes are most active. Anopheles darlingi and Anopheles nuneztovari were the most common species collected by both methods, whereas Anopheles marajoara was more abundant according to the HLC method. The MMLP trap was more efficient for collecting An. nuneztovari [63%, confidence interval (CI): 2.53] than for collecting An. darlingi (31%, CI: 1.57). There were significant correlations (p < 0.01) between the two methods for An. darlingi [Pearson correlation (R2) = 0.65] and An. nuneztovari (R2 = 0.48). These preliminary results are encouraging for further investigations of the use of the MMLP trap for monitoring anopheline populations in remote malaria-endemic areas in the Amazon Basin. PMID- 22666870 TI - Serological detection of St. Louis encephalitis virus and West Nile virus in equines from Santa Fe, Argentina. AB - St. Louis encephalitis virus (SLEV) and West Nile virus (WNV) present ecological and antigenic similarities and are responsible for serious human diseases. In addition, WNV is a significant pathogen in terms of equine health. The purpose of our study was to analyse the seroprevalence of SLEV and WNV in equine sera collected in Santa Fe Province, Argentina. The seroprevalence determined using the plaque reduction neutralisation test was 12.2% for SLEV, 16.2% for WNV and 48.6% for a combination of both viruses. These results provide evidence of the co circulation of SLEV and WNV in equines in Santa Fe. PMID- 22666871 TI - Emergence and characterisation of vanB vancomycin-resistant Enterococcus faecalis in Rio de Janeiro, Brazil. AB - Here we describe the detection and characterisation of three isolates of vancomycin-resistant VanB-type Enterococcus faecalis. Sequence analysis suggested that these isolates harboured the vanB1 gene. The isolates were susceptible to the majority of antimicrobial agents tested, with the exception of chloramphenicol, erythromycin and vancomycin, and showed distinct profiles of high-level resistance to aminoglycosides. Analysis of the clonal relatedness of the vanB E. faecalis isolates showed similar pulsed-field gel electrophoresis profiles. To our knowledge, this is the first report of the occurrence of enterococcal strains carrying vanB genes in Brazil. PMID- 22666872 TI - Helicobacter pylori vacA and cagA genotypes in patients from northeastern Brazil with upper gastrointestinal diseases. AB - Helicobacter pylori causes chronic gastric inflammation and significantly increases the risk of duodenal and gastric ulcer disease and distal gastric carcinoma. In this study, we evaluated the Helicobacter pylori vacA and cagA genotypes in patients from a Brazilian region where there is a high prevalence of gastric cancer. Polymerase chain reaction (PCR) was used to investigate vacA mosaicism and cagA status in the gastric mucosa of 134 H. pylori-positive patients, including 76 with gastritis: 28 with peptic ulcer disease and 30 with gastric cancer. The s1m1 variant was the predominant vacA genotype observed, whereas the s1 allele was more frequently observed in patients with more severe diseases associated with H. pylori infection [p = 0.03, odds ratio (OR) = 5.72, 95% confidence interval (CI) = 1.15-38.60]. Furthermore, all of the s1 alleles were s1b. Mixed vacA m1/m2 strains were found more frequently in patients with gastric cancer and a cagA-positive status was significantly associated with gastric cancer (p = 0.016, OR = 10.36, 95% CI = 1.35-217.31). Patients with gastric cancer (21/21, 100%, p = 0.006) or peptic ulcers (20/21, 95%, p = 0.02) were more frequently colonised by more virulent H. pylori strains compared to gastritis patients (41/61, 67.2%). In conclusion, in the northeastern of Brazil, which is one of the regions with the highest prevalence of gastric cancer in the country, infection with the most virulent H. pylori strains, carrying the cagA gene and s1m1 vacA alleles, predominates and is correlated with more severe H. pylori-associated diseases. PMID- 22666873 TI - Vectorial capacity, basic reproduction number, force of infection and all that: formal notation to complete and adjust their classical concepts and equations. AB - A dimensional analysis of the classical equations related to the dynamics of vector-borne infections is presented. It is provided a formal notation to complete the expressions for the Ross' Threshold Theorem, the Macdonald's basic reproduction "rate" and sporozoite "rate", Garret-Jones' vectorial capacity and Dietz-Molineaux-Thomas' force of infection. The analysis was intended to provide a formal notation that complete the classical equations proposed by these authors. PMID- 22666874 TI - Study design may explain discrepancies in GB virus C effects on interferon-gamma and interleukin-2 production and CD38 expression in T lymphocytes. PMID- 22666876 TI - Pathways to El Norte: origins, destinations, and characteristics of Mexican migrants to the United States. AB - The geography Mexican migration to the U.S. has experienced deep transformations in both its origin composition and the destinations chosen by migrants. To date, however, we know little about how shifting migrant origins and destinations may be linked to each another geographically and, ultimately, structurally as relatively similar brands of economic restructuring have been posited to drive the shifts in origins and destinations. In this paper, we describe how old and new migrant networks have combined to fuel the well-documented geographic expansion of Mexican migration. We use data from the 2006 Mexican National Survey of Population Dynamics, a nationally representative survey that for the first time collected information on U.S. state of destination for all household members who had been to the U.S. during the 5 years prior to the survey. We find that the growth in immigration to southern and eastern states is disproportionately fueled by undocumented migration from non-traditional origin regions located in Central and Southeastern Mexico and from rural areas in particular. We argue that economic restructuring in the U.S. and Mexico had profound consequences not only for the magnitude but also for the geography of Mexican migration, opening up new region-to-region flows. PMID- 22666877 TI - Obituary of a very special doctor, Dr Jan de Kraker (October 18, 1944 to January 19, 2012). PMID- 22666878 TI - Redefining public health in New York City. PMID- 22666879 TI - City life takes its toll on Sao Paulo's residents. PMID- 22666880 TI - The role of discovery DMPK scientists in industry: where do we go from here? PMID- 22666881 TI - Battling drug addiction in Bangalore. PMID- 22666882 TI - Putting dignity to work. PMID- 22666883 TI - Pay civilian Vietnam war nurses. PMID- 22666884 TI - Aged care, aged care, aged care! PMID- 22666885 TI - Policy, scope of practice and the 'agony of the moment'. PMID- 22666886 TI - Fraud fighters mine data: Auditors pave new path with aggressive investigative tactics. PMID- 22666887 TI - [Fever of unknown origin and digestive hemorrhage]. PMID- 22666888 TI - Abstracts of the Canadian Digestive Diseases Week and the Annual CASL Winter Meeting, February 24-27, 2012, Montreal, Quebec, Canada. PMID- 22666889 TI - The nurse education imperative. PMID- 22666890 TI - Taste of home: lawmakers are balancing strict food safety laws with policies to encourage small food entrepreneurs. States, feds see food safety roles differently. PMID- 22666891 TI - Fighting against chronic obstructive pulmonary disease. PMID- 22666892 TI - Saving money and improving care by integrating health care. PMID- 22666893 TI - Reducing strokes by streamlining care. PMID- 22666894 TI - Health information technology and privacy. PMID- 22666895 TI - Chemotherapy treatment options and policies. PMID- 22666896 TI - Understanding and addressing the impact of autism on the family. AB - Children and adults with autism spectrum disorders (ASDs) have needs that challenge our systems of care. A new study estimates ASDs cost more than $126 billion each year in the U.S.--an amount that reflects both the costs of providing educational and medical services as well as the costs of not intervening early and effectively enough to prevent lifelong disability. This Issue Brief summarizes the implications of childhood autism for parental employment and earnings, and analyzes whether community-based services can reduce costly, psychiatric hospitalizations of children with ASDs. PMID- 22666897 TI - Servicemembers' Group Life Insurance Traumatic Injury Protection Program- genitourinary losses. Final rule. AB - The Department of Veterans Affairs (VA) is issuing this final rule that amends the regulations governing the Servicemembers' Group Life Insurance Traumatic Injury Protection (TSGLI) program by adding certain genitourinary (GU) system losses to the TSGLI Schedule of Losses and defining terms relevant to these new losses. This amendment is necessary to make qualifying GU losses a basis for paying TSGLI benefits to servicemembers with severe GU injuries. The intended effect is to expand the list of losses for which TSGLI payments can be made. This document adopts as a final rule, without change, the interim final rule published in the Federal Register on December 2, 2011. PMID- 22666898 TI - Moving forward with wellness incentives under the Affordable Care Act: lessons from Germany. AB - Health care payers in the United States and abroad have used wellness incentives as a tool to improve health and reduce costs. In Germany, public insurers operate many such programs. Participation nearly doubled between 2004 and 2008, reaching one-quarter of the publicly insured population. An evaluation of one large wellness program there found that it reduced costs. However, population-level survey data also suggest that individuals with low incomes or poor health are less likely to enroll. In the United States, the Affordable Care Act raised the maximum allowed size of wellness incentives, which could lead to wide differences in insurance premiums between users and nonusers of programs, and may risk reintroducing a form of medical underwriting. The German experience confirms the cost-saving potential of programs, but also suggests that they should be evaluated rigorously to ensure they do not disadvantage those with health problems or low incomes. PMID- 22666899 TI - Re: neuroscience in Nazi Europe part I: eugenics, human experimentation, and mass murder. Can J Neurol Sci. 2011; 38:696-703. PMID- 22666900 TI - Lumbar radiculopathy-mimicking cortical infarction of the precentral region. PMID- 22666901 TI - Cognitive and mood profile of Sturge-Weber Syndrome affecting the thalamus. PMID- 22666902 TI - Is the treatment of multiple sclerosis headed in the wrong direction? PMID- 22666903 TI - Pediatric neurology training in Canada: current status and future directions. AB - BACKGROUND: Child neurology training in Canada has changed considerably over time, with increasing requirements for standardized teaching of the fundamentals of child neurology and the CanMEDS competencies. We sought to determine the current status of child neurology training in Canada as well future directions for training. METHOD: A web-based survey was sent to program directors (PD's) of active pediatric neurology training programs. General questions about the programs were asked, as well as about success at the Royal College of Physicians and Surgeons of Canada (RCPSC) exam, breakdown of rotations, views on CanMEDS roles and questions on the future of pediatric neurology. RESULTS: 9/9 PD's completed the survey. 96.5% of all trainees successfully passed their RCPSC exam from 2001-2006. Breakdowns of the number and type of rotations for each year of training were provided. All CanMEDS roles were deemed to be important by PD's and programs have developed unique strategies to teach and assess these roles.92.6% of trainees chose to go into academic practice, with the most popular subspecialty being epilepsy. All PD's favour joint training sessions particularly for neurogenetics and neuromuscular disease. Overall, PD's suggest recruitment for future child neurologists at the medical student level but are divided as to whether we are currently training too few or too many child neurologists. CONCLUSIONS: This survey provides a view of the current state of pediatric neurology training in Canada and suggestions for further development of post graduate training. In particular, attention should be given to joint educational programs as well as urgently assessing the manpower needs of child neurologists. PMID- 22666904 TI - High resolution electron microscopy of crystalline polymer wedges. AB - High resolution electron micrographs (HREM) of wedge-shaped crystalline samples of the polydiacetylene 1,6-di(N-carbazolyl)-2,4-hexadiyne (DCHD) are compared to quantitative predictions of image contrast obtained from dynamical electron scattering theory. Multislice calculations using experimentally determined instrument operating parameters make it possible to interpret the variation in HREM image contrast as a function of crystal thickness. Pendellosung plots of the intensity of the main beam and the scattered beams as a function of thickness corroborate characteristic features in the lattice images including extinctions and half-spacings. The position of these contrast features with respect to the edge of the polymer crystal wedge are compared to the theoretical calculations and used to estimate the height profile. This profile is then compared to wedge height profiles measured with scanning probe microscopy (SPM). The two approaches give similar results for DCHD crystal thicknesses below 50 nm. PMID- 22666906 TI - Measurement of elastic strains and small lattice rotations using electron back scatter diffraction. AB - A method is presented for the determination of elastic strains from electron back scatter diffraction patterns, which are obtained at high spatial resolution, from bulk specimens in a scanning electron microscope. It is estimated that the method is sensitive to strains of the order of 0.02%. Strains in Si(1-x)Ge(x) epitaxial layers grown on planar Si substrates were measured for x from 0.2 to 0.015, there being excellent agreement with X-ray diffraction results. Small lattice rotations can also be measured, the technique being sensitive to rotations of 0.01 degrees, which offers an improvement of approximately two orders of magnitude from the more usual EBSD measurements of misorientation. Small lattice rotations were measured in Si(0.85)Geo(0.15) grown on a patterned Si substrate and were consistent with elastic relaxation of the epilayer strain energy. PMID- 22666905 TI - Determination of scattering structures from spatial coherence measurements. AB - A new method of structure determination and microscopic imaging with short wavelength radiations (charged particles, X-rays, neutrons), based on measurements of the modulus and the phase of the degree of spatial coherence of the scattered radiation, is developed. The underlying principle of the method- transfer of structural information about the scattering potential via spatial coherence of the secondary (scattering) source of radiation formed by this potential--is expressed by the generalization of the van Cittert-Zernike theorem to wave and particle scattering [A.M. Zarubin, Opt. Commun. 100 (1993) 491; Opt. Commun. 102 (1993) 543]. Shearing interferometric techniques are proposed for implementing the above measurements; the limits of spatial resolution attainable by reconstruction of the absolute square of a 3D scattering potential and its 2D projections from the measurements are analyzed. It is shown theoretically that 3D imaging with atomic resolution can be realized in a "synthetic aperture" electron or ion microscope and that a 3D resolution of about 6 nm can be obtained with a "synthetic aperture" X-ray microscope. A proof-of-principle optical experiment is presented. PMID- 22666907 TI - Local quantification of the composition in GaAs/Al(x)Ga(1-x)As structures by thickness fringe analysis. AB - The increase of the complexity in semiconductor structures raises more and more the need for local evaluation techniques. For example, laser structures with graded-index waveguides are now widespread, but the characterisation of the shape of the gradient is still empirical. In this study, we use transmission electron microscopy (TEM) for the local determination of the chemical composition of GaAs/Al9x)Ga(1-x)As semiconductor laser structures, by quantifying the variation of the thickness fringe profiles with the aluminium content on wedge shaped samples. Contrary to former studies, the presented method uses experimental profiles for calibration. The quantification procedure is thus greatly simplified since no simulation program is needed. Measurements can be performed over distances of more than 1 microm with a spatial resolution of 1 nm, at any depth of the sample. The precision obtained is about +/- 0.03 for the aluminium content x, and the results show the potential of the method for the assessment of semiconductor layer structures. PMID- 22666908 TI - Real image resolution of SEM and low-energy SEM and its optimization: distribution width of the total surface emission. AB - The real point resolution of an SEM image is treated in a two-dimensional model where the decisive quantity is the root-mean-square distance of the emitted electron from the pixel centre. This quantity is computed taking into account the direct illumination of the specimen surface by the primary spot the dimensions of which are given by the electron optical column and the indirect illumination from a virtual source of the backscattered electrons in the specimen depth the properties of which depend on the specimen. Because the second order movement of the full distribution is considered here instead of some measure of the central narrow peak of secondaries, the backscattered electron influence significantly deteriorates the resulting resolution. Reasonable approximations regarding both contributions, particularly the Monte-Carlo modelling of the backscattering process by algorithms providing acceptable results down to 1 keV and the approximate relations describing the secondary and backscattered electron emission again down to 1 keV, enabled us to bring the considerations up to numerical results for some typical instruments, namely a "cheap" SEM, a "top" SEM and a low-energy SEM (LESEM) adapted from the cheap SEM by using the cathode lens. The optimum landing energy providing the best point resolution, computed for the individual chemical elements, falls into the range 1 to 5 keV for the cheap SEM and it remains around 1 keV (with some uncertainty caused by the approximations mentioned) for both the top SEM and LESEM. Similarly, the real resolution for the elements ranges between 16 and 45 nm when the cheap SEM with a 3.4 nm nominal spotsize at 30 keV is used, between 3.5 and 9 nm for the 0.7 nm top SEM and between 5.5 and 7 nm for the cheap SEM adapted to LESEM. PMID- 22666909 TI - Electron energy dependence of characteristics of fluorescent plates for ultrahigh voltage electron microscopes. AB - The characteristics of fluorescent plates for high energy electron beams (0.5-2.0 MeV) are examined. The thickness and the optical transparency of plates strongly affect the luminous broadening and intensity. The spatial luminous broadening in fluorescent plates is measured and is simply represented by the rise width of a knife edge image. When the thickness is much smaller than the range of incident electrons, the rise width is 1/4-1/5 of the thickness in the case of YAG single crystal plates that are transparent for light, while the rise width is nearly equal to the thickness for the packed P22 powder plates that are opaque for light. To suppress the luminous broadening under 50 microm, the thickness of YAG plates has to be thinner than 250 microm in the energy region around 2 MeV. Under the same condition of the rise width, the luminous intensity of YAG plates is twice as high as that of the P22 plates. PMID- 22666910 TI - TEM-tomography of FAU-zeolite crystals containing Pt-clusters. AB - A method for preparing ultrathin sections (- 20 nm) of inorganic solids has been developed using ultramicrotomy of resin-embedded crystal fragments. Undamaged crystals, oriented along a crystallographic direction, could be imaged with transmission electron microscopy (TEM) at a resolution better than 0.5 nm. The true internal structure of the crystals could be investigated by imaging the second in a series of at least three consecutive ultrathin sections. Such TEM tomography proved that Pt-ion exchanged FAU zeolite crystals, after reduction and oxidation, are occupied internally and randomly of large platinum clusters mainly in the {111-twin planes. TEM-tomography could be useful in man made nanostructures like semiconductors, epitaxial thin films, hard metal coatings, ceramics, catalysts, and biomaterials. PMID- 22666911 TI - Mostly books. PMID- 22666912 TI - Extension of crystallographic image processing to quasicrystals. AB - It is shown how crystallographic image processing, which is commonly used to enhance the quality of structural images of crystals, can be extended to quasicrystals. The use of the technique is demonstrated on an image of an icosahedral phase. PMID- 22666913 TI - Voltage-center and coma-free alignment for high-resolution electron microscopy. AB - Recently, it has become possible to carry out routinely a coma-free alignment with the aid of a personal computer. However, a coma-free alignment is only attained with a sacrifice of a voltage-center alignment, since both alignment procedures use the same beam deflectors above an objective lens. In this paper we overcome this difficulty by realizing the method proposed by Yanaka et al. [Proc. 8th Int. Congr. on Electron Microscopy, Canberra, 1974, Vol. 1, p. 128], where a coma-free alignment is carried out by using beam deflectors above the objective lens followed by a voltage-center alignment by adjusting beam deflectors below the objective lens. It is demonstrated that a voltage-center and coma-free condition can be achieved even for a 6-microm off-axis imaging which causes an appreciable difference between voltage-center and coma-free directions. PMID- 22666914 TI - A pattern recognition technique for the analysis of grain boundary structure by HREM. AB - A pattern recognition technique for the detection of structural units in high resolution images of interfaces is described. The technique uses cross correlation functions as a means of locating atomic patterns characteristic for an interface and as a measure of similarity between related units. Application is not limited to periodic, or even to planar interfaces. Characteristic structural units can be extracted from an experimental image and some important parameters such as mirror or mirror glide symmetry, and rigid body displacements can be determined without knowledge of the imaging parameters. The technique allows an image of a structural unit with reduced specimen noise to be obtained by averaging over several similar units, even if a boundary is not periodic and not planar. PMID- 22666915 TI - On the many advantages of local-electrode atom probes. AB - Local extraction electrodes offer several crucial advantages for operation of atom probes. Because of the proximity of the local extraction electrode to the specimen, the electric field produced at the specimen apex by a given voltage is enhanced and the voltage required for field evaporation is reduced. In a voltage pulsed atom probe, the absolute magnitude of the energy uncertainty is correspondingly reduced. High mass resolution (m/deltam > 1000) may therefore be obtained by accelerating the evaporated ions to a greater total potential after the local extraction electrode. The low extraction voltage may also be pulsed rapidly (100 ps rise time) and at high repetition rates (up to 10(5) pulses per second) using currently available solid-state pulsers. Furthermore, a local electrode and intermediate electrodes may be used as optical elements to control the image magnification. All of these benefits may be applied to any type of atom probe. Local-electrode atom probes (LEAP) should be especially advantageous for developing three-dimensional atom probes with high mass resolution and a large field of view. A sample has been developed that consists of many microtips formed on a planar sample using ion beam mask etching. Microtip samples are especially suited to LEAP. Analysis of electrically insulating samples may also be possible with microtip samples in a LEAP. This combination of features suggests flexible, high speed, high mass resolution atom probes that can work with either conventional needle-shaped specimens or the new style of planar microtip specimens. PMID- 22666916 TI - Wiener-filter enhancement of noisy HREM images. AB - The use of Wiener filters to restore noisy HREM images is discussed, exploiting the fact that the noise spectrum can be rather simply estimated. Conventional Wiener, Cannon, parametric versions of these and a random-phase form are found to be very effective. Quantitative analysis indicates that the signal-to-noise ratio is improved by a factor of 3-7, with better results for larger pictures. Such filtering techniques should have rather wide applicability in electron microscopy, and could be applied on-line with TV systems. PMID- 22666917 TI - Analysis of grain boundary dislocations by large angle convergent beam electron diffraction. AB - Large angle convergent beam electron diffraction (LACBED) is used to analyse secondary dislocations in sigma3 and sigma9 grain boundaries in silicon. By selecting reflections from crystal planes common to the adjoining grains, LACBED images are insensitive to the boundaries except where dislocations are present. The dislocation images are closely similar to those for dislocations in single crystals and can be analysed by standard Cherns-Preston rules. It is shown that, for both boundaries, sufficient common reflections can be selected for a complete analysis, and that dislocations can be analysed assuming integer values of g x b, implying that the Burgers vectors are Displacement Shift Complete (DSC) lattice vectors. For both sigma3 and sigma9 boundaries, DSC dislocations are identified which are specific to these boundaries. The experimental conditions for the analysis of grain boundaries are explained, and the extension of the method to other coincidence boundaries is discussed. PMID- 22666918 TI - Unconventional immuno double labelling by energy filtered transmission electron microscopy. AB - A new method of immuno double labelling of biological specimens with a very high spatial resolution is presented. The advantage over conventional techniques is the possibility of using two very small labels leading to higher labelling efficiency, better penetration into the specimen and reduced steric hindrance between labels at closely spaced sites. The two labels are distinguished by their electron energy loss spectra using principal component analysis and then identified by comparison with an external standard using discriminant function analysis. The method is tested on samples of insect flight muscle labelled with 8 nm colloidal gold and silver and the statistical reliability of the classification is assessed. Extensions of the method are suggested and its potential for biological research is discussed. PMID- 22666919 TI - A high efficiency annular dark field detector for STEM. AB - A new high efficiency annular dark field (ADF) detector for an HB501 STEM (Scanning Transmission Electron Microscope) has been constructed and tested. This detector uses a single crystal YAP scintillator and a solid quartz light pipe extending from the scintillator (inside the vacuum) to the photomultiplier tube (outside the vacuum). A factor of approximately 100 improvement in signal relative to the original detector has been obtained. This has substantially improved the signal to noise ratio in the recorded high resolution ADF-STEM images. PMID- 22666920 TI - Reconstruction of the projected crystal potential from a periodic high-resolution electron microscopy exit plane wave function. AB - A method based on a simulated annealing algorithm is applied for the reconstruction of the projected crystal potential belonging to a periodic high resolution electron microscopy exit plane wave function. Using simulated exit plane wave functions of GaAs at different specimen thicknesses, the convergence behaviour and the accuracy of the algorithm are investigated. It is demonstrated that the reconstruction is possible even under strongly non-linear scattering conditions at small specimen thicknesses. Further, the convergence of the algorithm to an ambiguous solution beyond a certain specimen thickness is discussed. PMID- 22666921 TI - Structure projection retrieval by image processing of HREM images taken under non optimum defocus conditions. AB - A direct method for retrieval of the projected potential from a single HREM image of a thin sample is presented. Both out-of-focus and astigmatic images can be restored. The defocus and astigmatism values are first determined from the Fourier transform of the digitised HREM image. Then a filter is applied which reverts the phases of those Fourier components which have been reversed by the Contrast Transfer Function (CTF). The method has been incorporated into the CRISP image processing system. It can be applied on any sample, crystalline or amorphous. From thin crystalline areas the projected symmetry can be determined and a further improvement achieved by imposing the symmetry exactly. This compensates for the effects of crystal tilt. Five HREM images of a thin crystal of K(8-x)Nb(16-x)W(12+x)O80 (x = 1), taken with different defocus and astigmatism values, were processed. Only one, taken near Scherzer defocus, was directly interpretable before image processing. After processing, all images showed the projected potential of the structure. Using data to 2.77 angstroms resolution, all heavy (Nb/W) atom positions were found in every image, within on average 0.15 angstroms of the positions determined by single crystal X-ray diffraction. In the HREM images taken under non-optimum defocus conditions, also the potassium atoms in the tunnels of the structure were found. PMID- 22666922 TI - Optimum condition of convergent beam illumination for observation of local structure by high resolution transmission electron microscopy. AB - We propose the convergent beam illumination as a technique for the local structural analysis by high resolution transmission electron microscopy. The image contrast is lower in the convergent beam illumination than in the parallel beam illumination because of the lower coherency. However the intensity oscillation around an atom image, which appears due to interference effect, is much reduced with the convergent beam illumination, and pseudo-images do not appear at termination of crystal periodicity. The convergent beam illumination, rather than parallel beam illumination, precisely reveals non-periodic local structures, such as interfaces, surfaces and fine particles, which are even embedded in a crystal. From theoretical analysis the optimum condition is derived as divergence of q(s )* = 0.44 and focus of delta(z)* = 1.35 in generalized coordinates. Using the convergent beam illumination the point resolution is improved by 20% compared to conventional parallel beam illumination. PMID- 22666923 TI - Stacked bilayer helices: a new structural organization of amphiphilic molecules. AB - Intriguing helical fibres can be created by self-assembly of simple chiral amphiphilic molecules. We study the parameters governing this spontaneous self organization by three-dimensional (3D) electron microscopy of the helical fibres embedded in a vitreous ice-matrix. Different stable helices are generated reproducibly using specific combinations of the control parameters in our system. All fibres with diameters less than 25 nm consist of a narrow stack of compartmented bilayers twisted into a left-handed helix. Our novel helical 3D reconstruction procedures in combination with specialized cryomicroscopical specimen preparation, can rapidly elucidate the structure of such helical assemblies. This approach may complement or even replace existing diffraction based methodologies. PMID- 22666924 TI - [Ethiopathogenesis of gastroesophageal reflux disease]. AB - The primary cause of the gastroesophageal reflux disease is the impairment of motility and not that of acidic secretion. The reflux disease develops when the balance between aggressive and defensive factors becomes disequilibriated. Among the aggressive factors the gastro-oesophageal (duodeno-gastro-oesophageal) reflux is classified. In its pathogenesis, the major role has the concentration of the hydrochloric acid, presence of bile and of pancreatic enzymes. These factors may be potentiated by the hiatal hernia, gastric dysmotility, insufficient pyloric competency, and subsequent duodeno-gastric reflux. Key factor in the development of the gastroesophageal reflux disease is the length of esophageal exposition to the refluxed gastric content. The role of duodenal content is not yet clear. Mucosal impairment probably comes from the synergistic effects of hydrochloric acid and the bile. The antireflux barrier, luminal clearance, and the tissue resistance may serve as protective factors. The first line of defence is the antireflux barrier--the retrograde flow of the gastric content is blocked by the competence of the lower esophageal sphincter and by the contractile activity of the diaphragm. Transition of epithels in the region of gastro-oesophageal junction is not yet fully understood. When inflammatory and reactive changes are found in the cardiac mucosa, the case is classified as carditis. Three potential mechanisms of incompetence in the region of gastro-oesophageal junction been described: Transient relaxation of the lower oesophageal sphincter, hypotension of the lower oesophageal sphincter, anatomical disruption of the gastro oesophageal junction, which is frequently connected with hiatal hernia. Majority of papers indicates that the essential causes of the gastroesophageal reflux disease are transient relaxations of the lower esophageal sphincter and diaphragm. In patients with massive reflux esophagitis, pressure of the lower esophageal sphincter is weak and amplitude of esophageal contractions is low. Gradient in the region of the lower esophageal sphincter is formed in the vicinity of the functioning valve, which is formed by musculo-mucosal fold located in transition of esophagus and stomach. In healthy persons, refluxed fluid is quickly removed from the esophagus, which is the second line of defence. Reduction of the frequency or the power of peristaltic contractions causes delayed esophageal clearance. Gravitation and neutralisation of acids by bicarbonates in saliva assist the clearance. Pathogenic processes can be augmented by the retardation of gastric emptying. Composition of the refluxed fluid reflects the seriousness of the disease. Two mechanisms of impaired esophageal emptying has been identified: Peristaltic dysfunction and "re-reflux" related to some hiatal hernias. The third line of defence is the less known and it is represented by "tissue resistance". The role of eicosanoids in the gastroesophageal reflux disease is not yet known because their levels do not correlate with the seriousness of the symptoms. Increased prevalence of the reflux disease during the last years is often correlated with decreased incidence of Helicobacter pylori infections. Ethiopathogenesis of the reflux disease is multifactorial and can include deficient antireflux mechanisms, frequency of reflux episodes, volume and effectiveness of the refluxed fluid, mucosal resistance, deficient esophageal clearance and emptying of the stomach. Among the serious factors may belong the frequency and magnitude of the gastro-oesophageal reflux, however, the key role probably plays the dysfunction of the lower esophageal sphincter. PMID- 22666925 TI - [Newer immunosuppressive agents and their place in current practice]. AB - The last decade has witnessed an expansion of the arsenal of new immunosuppressive agents to include several novel drugs and antibodies. The main indication of all these immunosuppressive agents is organ transplantation. In terms of its action, tacrolimus resembles cyclosporin A and is employed as the mainstay immunosuppressant or for what is referred to as rescue therapy in refractory rejection. Mycophenolate mofetil is an anti-metabolite replacing azathioprine in immunosuppressive protocols. Sirolimus is an agent for prophylactic use, either as part of a cyclosporin-based regimen to enhance the effect of cyclosporin or as an alternative of non-nephrotoxic immunosuppression to cyclosporin-based regimens; its indications are still being specified. Gusperimus could be used for anti-rejection therapy; however, it is not being used in this country as yet. Recently, two monoclonal antibodies against the IL-2 receptor, chimeric basiliximab and humanized daclizumab, have been employed. Both agents are of non-depletion type and are indicated for induction therapy in the early post-transplant period. PMID- 22666926 TI - [Interaction of mutations M235T of the gene for angiotensinogen and Taq I 8,000 in the gene for endothelin-1 at the onset of essential hypertension]. AB - BACKGROUND: Identification of mutations contributing to the pathogenesis of essential hypertension performs to understand deeper consequences of developing pathophysiological changes, to value individual risk of hypertension in the preclinical stages and, regarding the observed genotype, to choose optimum therapy. The aim of the study was to prove the existence of difference in double genotype occurrence of polymorphic candidate genes between normotensive and hypertensive subjects. METHODS AND RESULTS: A sample of Czech population (398 individuals), 192 normotensives (age of 45.87 +/- 3.0, BMI = 25.44 +/- 3.31 kg x m2) a 206 hypertensives (age of 48.71 +/- 8.42, BMI = 27.18 +/- 4.16 kg x m(-2)) was genotyped at angiotensinogen (AGT, M235T polymorphism, exon 2) and endothelin 1 (EDN-1, Taq I 8000 polymorphism, intron 4) genes by PCR methods. Experimental schedule was case-control. Chi2 and Fisher-exact test were used for statistical analyses. M-allele of angiotensinogen gene was associated with essential hypertension (p = 0.0111). Allele (-) alone at endothelin-1 gene was associated with essential hypertension with marginal significance (p = 0.0622). A significant loss of heterozygotes MT (M235 AGT) at homozygote (--) at endothelin 1 gene (p = 0.0025) as well as a significant increase of allele (-) of endothelin 1 gene at homozygote MM at angiotensinogen gene (p = 0.0034) were found. CONCLUSIONS; Interaction of two polymorphic genetic variants of angiotensinogen and endothelin-1 genes was found. From the pathophysiological point of view, the fact may be explained as a stream to compensate the influence of variability of other genes more causatively conditioning essential hypertension. PMID- 22666927 TI - [Prenatal diagnosis of lysosomal enzymopathies in the Czech Republic]. AB - BACKGROUND: Prenatal diagnosisi represents the important fprm of prevention of the inherited metabolic diseases and its accessibility becomes the most effective assistance to involved families. The aim of the study was to introduce prenatal diagnosis of major inherited lysosomal disorders of the group of lipidoses, micopolysaccharidoses, glycoproteinoses, and mucolipidoses. METHODS AND RESULTS: Methodological approach is based on the activity estimation of the specific lysosomal hydrolases that are missing or inactive. Methods were extended by a set of supportive analyses, namely by ultrastructural identification of the lysosomal storage of the non-degraded substrate, DNA analysis showing mutation in the family or by biochemical analysis of the amniotic fluid. Uncultured cultured chorionic villi, cultured amniotic fluid cells yand samples of the amniotic fluid were examined. Altogether 17 pregnancies at risk for seven different lysosomal enzymopathies were followed: GM2 gangliosidosis (2 cases), Fabra disease (3 cases), Krabbe disease (1 case), Niemann-Pick disease type A (1 case), mucopolysaccharidosis I (5 cases), mucopolysaccharidosis II (4 cases), mucolipidosis II (I-cell disease) (1 case). Profound deficiency of enzyme activities (alpha-galactosidase A in fabry disease, galactocerebrosidase in Krabbe disease, alpha-iduronidase in mucopolysaccharidosis I) was identified in three pregnancies, which were terminated on the mother's decision. The diagnose was confirmed by the biochemical analysis of tissues of aborted foetuses. In two of them (Fabry disease, mucopolysaccharidosis I) ultrastructural sings of storage werw proved. In two cases the foetal heterozygote state was identified. In case at risk for Niemann-Pick disease type A, the diagnosis was confirmed also by DNA analysis. In the pregnancy at risk for Fabry disease, heterozygous state was confirmed indirectly according to the difference of alpha-galactosidase activities in cultured and uncultured cells. A set control values of enzyme activities in individual types of processed material (native and cultured chorionic villi, cultured amniocytes, and amniotic fluid supernatant) has been established. CONCLUSIONS: Inherited lysosomal enzymopathies represent important indication for prenatal diagnosis available now in our department. Condicio sine qua non is the biochemical or molecular genetic confirmation of diagnosis in the family involved. PMID- 22666929 TI - Ever increasing role of laparoscopy in cancer. PMID- 22666928 TI - [Epidemiological analysis of patients with psoriasis hospitalised at 1st Dermatovenereologial Clinic LF UK and FN in Bratislava in years 1994 to 1998]. AB - BACKGROUND: Incidence of psoriasis is variable and represents about 2% of the population in Europe and in Northern America. The aim of the study was to analyse epidemiological situation in patients with psoriasis, hospitalised in years 1994 1998. METHODS: Using data accumulated at the 1st Dermatovenerologial clinic LF UK and FN, authors catamnestically selected information about patients hospitalised for psoriasis in years 1994-1998. The age of patients, their sex, beginning of the disease, prevalence in the family, and clinical symptoms according the PASI score were evaluated. RESULTS: In the followed period 720 patients with psoriasis were hospitalised (10.52%), 461 males, 259 females. The average age was 42.33 years in males and 40.72 years in females. Psoriasis type I was diagnosed in 81.32% of males and 76.56% of females. Most frequently the disease started in the age of 15 to 19 years, the second maximum was between 45 to 49 years in both genders (18.65% of males, 23.78% of females). In 24.58% the positive family anamnesis was reported. In 47.45% it was the first degree of the genetic transmission. The disease was more frequently transmitted from the father's side (68.36% than the mother's side (31.63%). In 22.59% the overpass of generation was seen. Average value of PASI score was 40.22, which represents the heavy form of psoriasis. CONCLUSIONS: Epidemiologic analysis has shown the high prevalence and seriousness of the disease of the hospitalised patients with psoriasis. Beginning of the disease culminates during two periods of life, it is more frequently transmitted from the father's side and it can overpass one generation both in vertical and horizontal line. PMID- 22666930 TI - Kappa statistics in the screening of malignancy of prostate. AB - The optimal upper limit of the normal range for prostate specific antigen (PSA) is suggested, but review of literature reveals that, malignancy of prostate can occur below that range and some benign prostatic diseases are occasionally associated with higher levels. The aim of the study is for early detection of prostatic malignancy. We tried to evaluate digital rectal examination (DRE), estimation of PSA and transrectal ultrasound (TRUS) guided core needle biopsy and histopathological examination in the patients. Seventy-two consecutive patients with lower urinary tract symptoms were taken in this retrospective study from January 2005 to February 2006. PSA level was measured by automated chemilumininescence system. Prostatic biopsies were taken for histopathological examination and stained with haematoxylin and eosin. Gleason grading was applied in case of adenocarcinoma of prostate. For detection of malignancy, sensitivity, specificity, predictive value for positive test and of negative test, percentage of false negatives and false positives, p-values, confidence interval and kappa statistical calculations were done. It was found 19 cases with PSA level > 4 ng/ml had benign diseases of prostate and one person having PSA level < 4 ng/ml had adenocarcinoma of prostate. Seven DRE positive cases had benign disease of the prostate and 5 DRE negative patients had adenocarcinoma of prostate. When compared, serum total PSA value alone and combined PSA and DRE, the later combined approach was found to be more useful. We recommend the study of DRE, PSA and TRUS guided core needle biopsy for detection of prostatic cancer at localised and potentially curable stage. PMID- 22666931 TI - Clinical profile of dengue during 2005 outbreak in Kolkata and predictive markers of dengue haemorrhagic fever. AB - Epidemics of dengue outbreak are frequent in south-east Asian countries. Dengue is a major cause of morbidity and mortality in this region. This prospective observational study was done at Dr BC Roy Memorial for Children during the outbreak in 2005 in Kolkata to know the clinical pattern of dengue cases and to find the possible markers of development of dengue hemorrhagic fever. Two hundred and eighty seropositive cases of dengue were included in the study. Among paediatric population, 5 to 10 years age group was most commonly affected. One sixth of the cases were from villages indicating the extension of the epidemic in rural areas. Abrupt onset of high fever, non-purulent conjunctival injection, erythematous lips, flushed appearance, myalgia, arthralgia, headache and thrombocytopenia were the predominant features. Rhinitis and pharyngitis were rarely found. Prolonged fever more than 7 days, flushed appearance, pharyngeal congestion, shock evidence, serous effusion, bleeding manifestations, thrombocytopenia, elevated liver enzymes and elevated PCV were associated with development of dengue haemorrhagic fever and dengue shock syndrome. PMID- 22666932 TI - Demographic, morphologic and aetiological profile of uveitis patients presenting in a tertiary eye hospital in Eastern India. AB - This prospective study was performed to find out the profile of newly diagnosed uveitis patients in a tertiary eye hospital in Eastern India over one year from August 2006 to July 2007. One hundred and sixty-one patients were included; 58 patients (36.02%) had anterior uveitis, 21 (13.04%) had intermediate uveitis, 56 (34.78%) had posterior uveitis and 26 (16.15%) had panuveitis. A specific diagnosis could be made in 50 patients (31.06%). The profile of uveitis patients in this study from Eastern India correlated with those published in studies from North and South India. PMID- 22666933 TI - Depression in intensive cardiac care unit. AB - Depression is known to occur in patients with heart disease and the intensive cardiac care unit (ICCU) environment adds to their worsening symptoms. The objective of the study was to determine depression in patients admitted to ICCU. A total of 30 patients admitted to ICCU with heart disease were taken for the study and were compared to patients with heart disease admitted in general medicine wards (except ICCU). The tool used was Beck's depression inventory (BDI). This study showed depression as assessed on BDI was statistically highly significant. The results showed that the patients in ICCU suffered from depression. PMID- 22666934 TI - Prevalence of methicillin-resistant Staphylococcus aureus and its antibiotic susceptibility pattern in a tertiary care hospital. AB - Methicillin-resistant Staphylococcus aureus (MRSA) emerged as a nosocomial pathogen in early 1960s, causing Increasing number of outbreaks in 19708, first reported in a teaching hospital in Malaysia in 1972, causing increased mortality, morbidity, and healthcare costs. Aim of this study is to screen out MRSA from various clinical samples and to see their antibiotic susceptibility pattern. From May 2008 to May 2009, 204 S aureus strains were isolated, out of which 114 (55.8%) were MRSA, and rest methicillin-sensitive Staphylococcus aureus (MSSA). Most of the MRSA strains were obtained from pus (45%) followed by urine (20.5%). Frequency of isolating MRSA were maximum in catheter tip (80%) followed by blood (66.7%) and pus (58.7%). MRSA strains were showing 100% sensitivity to vancomycin and Iinezolid, whereas 92.9% to teicoplanin. Therefore it is concluded that antibiotics other than vancomycin can be used as anti-MRSA agents after sensitivity test, as well as irrational and indiscriminate use of antibiotics can be avoided. PMID- 22666935 TI - Pattern of the haemoglobinopathy in the endemic and nearby provinces in Thailand, a note from then GIS pattern. AB - In Thailand, high prevalence of haemoglobin disorders has been reported. Millions of Thai people suffer from these diseases. This problem affects not only public health but also the economy of the country. Carrier detection, genetic counselling and prenatal diagnosis should be encouraged. Most of the programmes have been launched to the endemic provinces in the southern part of northeastern region of Thailand. However, due to the recent industrialisation in Thailand, the migration of the Thai population affects the pattern of haemoglobin disorder in this area. Here, the author performs a spatial analysis by Geographical Information System (GIS) using ArcExplorer Program on the database of the recorded prevalence of haemoglobin disorder in the endemic area and nearby provinces. The drift of the high prevalence from the central endemic area to the nearby provinces can be seen and support the migration effect of the population. Of interest, this observation can support the recent report on the rising prevalence of haemoglobin disorders in the non-endemic area of Thailand. PMID- 22666936 TI - A comparative study of status of RNTCP in tribal and non-tribal districts of Odisha. AB - To compare the RNTCP outreach in the tribal districts with that of non-tribal districts. The annual status reports on RNTCP was analysed to evaluate the performance in tribal districts and non-tribal districts. The case detection parameters were far better in the tribal districts than in the non-tribal districts. Treatment success was almost equal in the tribal districts to that of non-tribal districts. PMID- 22666937 TI - Impact of sex education on knowledge and attitude of adolescent school children of Loni village. AB - Reproductive capability is now established at earlier age. But the subject of adolescent sexuality is taboo in most societies. There is widespread ignorance about risks of unprotected sex, problems among adolescents. Unfortunately need of sex education is not perceived and fulfilled in India especially in rural areas. The present study was conducted to assess the need and demonstrate the impact of sex education among adolescent school children. The impact of sex education workshop was tested by analysing pre- and postintervention questionnaire. The felt need of sex education increased considerably and the knowledge regarding contraceptives increased from manifolds after the intervention. There was significant increase in knowledge about menstrual hygiene, sexually transmitted diseases, etc, after sex education workshop. This study concludes that there is intense need of sex education and it has significant impact on knowledge of adolescent school children. PMID- 22666938 TI - Cancers of unknown primary site. AB - A patient is considered to have tumour of unknown primary origin when a tumour is detected at one or more metastatic sites and routine evaluation fails to identify a primary tumour. Metastatic carcinoma of unknown primary origin constitutes 3 15% of all cancers and poses a major diagnostic and therapeutic dilemma, because cancer treatment is typically directed at the specific primary tissue type. The regression or dormancy of the primary tumour, the development of early, uncommon systemic metastases and the resistance to therapy are hallmark of this heterogeneous clinical entity. Still no consensus exists on whether cancer of unknown primary site is simply a group of metastatic primaries or a distinct entity with specific genetic and phenotypic characteristics that define it as "primary metastatic disease". In this review we briefly highlight the biologic behaviour and genetic aberrations of unknown primary tumours. PMID- 22666939 TI - Doctor and criminal negligence. AB - Consumer Protection Act 1986 was finally made applicable to the medical services. Accordingly, any breach in the line of medical treatment make the treating physician to pay the damages caused to the patient. At times, the negligence will be so grave that a criminal case may be booked against the erring doctor. Doctors today, not only has to be well versed with the medical knowledge, but they also has to have a sound legal knowledge. The article revolves around the various aspects of medical negligence quoting the Supreme Court judgment and concluded with the precautions that one may take to avoid medical negligence. PMID- 22666940 TI - Mushrooms and poisoning. AB - The mushrooms are probably one of the oldest consumption of mankind having mythological and spiritual significance apart from being a great delicacy. Its poisoning is a common yet poorly recognised. There are more than 2000 varieties which are edible, and nearly 80 varieties are non-edible (or poisonous) type. Not only they resemble some of the edible types, they even grow long with them. Most of the toxic events go unnoticed, yet, sometimes it may be life threatening as some mushrooms are one of the most toxic fungi known to manking. Awareness is pobably the only prevention. PMID- 22666941 TI - Waist cancer: report of two cases. AB - Saree is a type of female costume unique to Indian subcontinent. This includes a superficial cloth and a skirt underneath which is fastened securely to the waist by a cord. Persistent and long-term wearing of this costume has resulted in waist dermatoses. This waist dermatoses giving rise to malignancy is being reported here and 'saree cancer' is the term used to this entity of waist cancer. Here two cases of waist cancer are reported. PMID- 22666942 TI - Postoperative intussusception following repair of eventration of diaphragm--two case reports. AB - Two patients of postoperative intestinal obstruction following repair of eventration of diaphragm, subsequently diagnosed as postoperative intussusception managed successfully, are reported. Absence of common features of intussusception led to delay in the diagnosis. Rarity of this phenomenon and incidentally two consecutive cases of postoperative intussusception occurring after repair of eventration of diaphragm prompted to report these two cases. PMID- 22666943 TI - Ovarian germ cell neoplasm in a true hermaphrodite. AB - True hermaphrodites are extremely rare. The incidence of malignancies in cases of true hermaphrodites range between 1.9-2.6%, and is almost exclusively associated with cytogenetic mosaicism. All of the malignancies reported till date are germ cell neoplasms, namely, seminoma, gonadoblastoma or teratoma, mostly in the male phenotype. In this case we Illustrate a rare occurrence of a dysgerminoma of the ovary, its treatment and responses, in a 35-year-old true hermaphrodite with a female phenotype, and cytogenetic mosaicism. PMID- 22666944 TI - Bilateral acute foot drop following lumbar disc herniation--a case report. AB - Cauda equina compression and acute unilateral foot drop are commonly described associations with prolapsed intervertebral lumbar disc. The bilateral acute foot drop however is a rare occurrence. A 45-year-old adult male labourer presented with 1 month history of low backache, with acute exacerbation 1 day later. He developed acute bilateral foot drop and urinary retention within 2 hours. An urgent magnetic resonance imaging (MRI) revealed large central disc prolapse at L3-L4 level with significant canal stenosis. He was operated on emergent basis following which he had progressive neurological improvement. PMID- 22666946 TI - Early detection of cancer cervix in a 35-year-old woman. PMID- 22666945 TI - Anhidrotic ectodermal dysplasia presenting as atrophic rhinitis. AB - Ectodermal dysplasia is a complex group of familial disorders with numerous clinical characteristics, with an incidence of 7 in 10000 born alive children. Ectodermal dysplasia affects structures of ectodermal origin like the skin and its appendages as well as other non-ectodermal structures. The most common sites of involvement are the defects in the skin, hair, teeth, nails and sweat glands,which are of ectodermal origin. Though the dermatologists and paediatricians often manage such cases, we report one case of ectodermal dysplasia presenting with atrophic rhinitis. PMID- 22666947 TI - Managing diabetes in India: paradigms in care--outcomes and analysis in a comprehensive, clinical practice survey of Indian physicians. AB - Diabetes continues to be a pandemic despite huge strides in the awareness and management of the condition. The incidence of diabetes has been projected to rise by almost 170% in most of the developing countries including India. Currently, about 50 million people suffer from diabetes in India with the figures expected to reach 87 million by the year 2030. To assess the management trends in India, a cross-section of doctors across all the major zones of the country were requested to answer a set of questions based on a case profile. Approximately 1000 doctors from all corners of India provided their feedback on various issues of diabetes management. The patient profile was that of an overweight 46-year-old Indian female with hypertension, diabetes and dyslipidaemia with a history of recurrent urinary tract infection (UTI). Almost 84.5% of doctors concurred with the diagnosis of metabolic syndrome for this patient. The awareness about diabetes being a comorbidity as well as a cause for recurrent UTI was high with 86% of doctors choosing diabetes as a cause for recurrent UTI. Around 94% of doctors chose metformin as the drug of choice for the management of this patient. A total of 74% of doctors chose the combination of metformin and sulfonylurea for the management of postprandial hyperglycaemia. Opinions were divided on the choice of drugs for the management of diabetes in a non-obese patient with 31% of doctors still choosing metformin as the drug of choice as per the American Diabetes Association 2009 guidelines and 66% of doctors choosing glimeperide as the first choice in a non-obese patient in concordance with the Association of Physicians of India/Indian College of Physicians (API/ICP) guidelines on diabetes. However, 95% of doctors unanimously chose metformin as the drug of choice in patients with abdominal obesity and diabetes. Almost 83% of doctors were aware that Indians have a genetic predisposition to diabetes due to an inherently smaller beta cell mass associated with insulin resistance. Majority of the physicians were also aware of the adverse effects of most of the antidiabetic drugs with 86% of the physicians identifying hydrochlorothiazide as the cause of worsening uric acid levels in diabetics, when used for the management of hypertension. Practice patterns in India generally conform to guidelines. The survey also demonstrated that majority of the physicians are aware of the different complexities associated with the management of diabetes. PMID- 22666948 TI - Off-trail in Oregon. Armed with CMS grant, Ore. lawmakers aim to cut Medicaid costs with coordinated ACO. AB - In an effort to battle soaring Medicaid costs, Oregon is experimenting with coordinated care organizations with the hopes of saving $11 billion over 10 years. Dr. George Brown, president and CEO of Legacy Health, says, "My prediction is that we will be successful. It will be a lot of hard work, but if we're not, it will be much worse." PMID- 22666949 TI - Got a better idea? Senators ask providers for fraud-fixing suggestions. PMID- 22666950 TI - Buoyed by outpatient growth. Despite hurdles, for-profits report revenue gains. PMID- 22666951 TI - Fire spreads. Congress wants more on Accretive. PMID- 22666952 TI - 'Enraged' by 30-day window. Groups call AHA out of touch with patients over medical-data delay. PMID- 22666953 TI - GPO industry: we're on track. PMID- 22666954 TI - One on one. Levinson talks Stark law, big data. Interview of Daniel Levinson by Joe Carlson. PMID- 22666955 TI - Providers feeling the heat? Vatican's rebuke of nuns may signal reform ahead. PMID- 22666956 TI - Unpleasant memories. Hospital billing, Medicare bankruptcy stories recall old times. PMID- 22666957 TI - Role models. Mass. safety net hospitals on cutting edge of reform implementation. PMID- 22666958 TI - The 2% solution. Health systems prepare for coming Medicare cuts. PMID- 22666959 TI - Hot Pot: How Barack Obama's medical-marijuana plans went up in smoke. PMID- 22666960 TI - Caught in the middle. Under tough scrutiny from the CMS over which patients should be admitted for care, hospitals are frustrated--and patients are fighting back. AB - As hospitals face growing pressure to reclassify inpatients to "observation" status, patients are the ones being hit with unexpected bills to pay what Medicare won't. One solution to the dilemma is a bill that would restructure the rules on when skilled-nursing care is paid for. "We have very broad-based support," says U.S. Rep. Joe Courtney (D-Conn.), left, one of the House sponsors. PMID- 22666961 TI - Booster shot. Proposed rate bump sees guarded support. PMID- 22666962 TI - Tweaking the system. Mass. bills call for move away from fee-for-service. PMID- 22666963 TI - Devicemakers push back. Proposed limits on adding tax to prices stir debate. PMID- 22666964 TI - United in California. SEIU, hospitals strike unique deal to work together. PMID- 22666965 TI - Transitional woes. Providers, health plans challenging states over reimbursement. PMID- 22666966 TI - Seeking expert advice. Organizations see no conflict of interest as IT veterans join firms' boards. PMID- 22666967 TI - Time for a turnaround. These trends certainly don't bode well for a healthy nation. PMID- 22666968 TI - Embracing the future. We need another Flexner report to shake up and restructure healthcare. PMID- 22666969 TI - Trauma in EMS. Emergency medical services system faces myriad challenges, including overhaul of reimbursement structure. PMID- 22666970 TI - Bracing for a crash. While IT outages are rare, providers need a plan. PMID- 22666971 TI - Estimated use of industrial chemicals in Connecticut. AB - BACKGROUND: Chemical exposures in the workplace are poorly documented and researched, yet appear to be widespread and with significant potential for impacting worker health. There are few reporting requirements for chemical usage on a national level. METHODS: Chemical usage reports and employment data from Massachusetts were categorized by manufacturing subsector. Connecticut employment was compared to Massachusetts data, with the employment fraction used to estimate chemical usage in Connecticut. RESULTS: The chemical manufacturing sector was estimated to use 620 million pounds of chemicals annually in Connecticut, and all other manufacturing sectors combined used an estimated 50 million pounds, with approximately half listed as carcinogens or reproductive hazards. Potential health effects are presented. CONCLUSION: Widespread chemicaluse underscores the need for the development and use of safer alternatives, as well as additional documentation of potential health effects. Physicians should be aware of potential chemical exposures for patients and provide preventive advice. PMID- 22666972 TI - Gout: what a pain in the neck. PMID- 22666973 TI - Apical hypertrophic cardiomyopathy associated with chronic hypertension: diagnostic and management implications. AB - Apical hypertrophic cardiomyopathy (HCM) is a rare variant of HCM in the non Japanese population (1% to 2%). Diagnostic dilemma occurs when this type of HCM is newly discovered in a patient previously diagnosed with left ventricular hypertrophy (LVH) secondary to hypertension. We describe an atypical presentation of an apical HCM in the setting of chronic hypertension (HTN) and review the literature of this rare variant of HCM. Our patient presented with chest pain and was found to have apical HCM with inducible apical ischemia and an abnormal blood pressure response to exercise. Multimodality imaging approach is proposed to evaluate the LVH when both apical HCM and hypertension are present given the impact of an accurate diagnosis on prognosis and management. PMID- 22666974 TI - Acute myeloid leukemia following solid organ transplantation: case report and comprehensive review. AB - Organ transplant recipients are at an increased risk for subsequent malignancies including hematologic malignancies. The development of acute myeloid leukemia (AML) after solid organ transplantation is a rare but well-documented event. It is thought to be a consequence of immune dysregulation secondary to the use of immunosuppressive agents. Herein, we present the management of a liver transplantation recipient who presented with AML and comprehensively review the relevant literature. A 59-year-old male patient presented with fever and cough eight years after an orthotopic liver transplantation for cirrhosis and hepatocellular carcinoma. He received methylprednisolone and mycofenolate mofetil (MMF) followed by tacrolimus and rapamycin as immunosuppression. Upon admission to our hospital, his peripheral blood demonstrated 34% blasts and pancytopenia. A bone marrow biopsy confirmed the diagnosis of myelodysplastic syndrome (MDS) in transformation to AML. He was treated with induction chemotherapy and his sirolimus was continued but he expired four weeks after from refractory disease. No specific guidelines exist for the treatment of AML in solid organ transplant recipients. Treatment should be individualized and concurrent use of chemotherapeutic and immunosuppressive agents should be carefully balanced. PMID- 22666975 TI - Odynophagia in sickle cell anemia: pain is not always a crisis. AB - This report describes the case of a 30-year-old African American male with sickle cell anemia who presented with odynophagia and chest pain. Clinical examination revealed tachypnea, conjunctival congestion, icterus, facial swelling, engorged neck veins, induration over the upper part of chest and arms and a right chest wall port-a-cath. Subsequent imaging revealed occlusion of both brachiocephalic veins and proximal superior vena cava with a metallic SVC stent in-situ. Recanalization was attempted but guidewires could not be passed across the site ofocclusion. He was then treated with catheter guided t-PA boluses delivered to the site of occlusion and oral anticoagulation. PMID- 22666976 TI - Simulation training for surgical residents in pediatric trauma scenarios. AB - INTRODUCTION: Pediatric trauma requires several medical professionals working together as a highly functioning team. Since critical pediatric medical events are rare, routine practice can be one method of ensuring that all members communicate and provide quality care. The goal of this study was to evaluate whether high-fidelity simulation training improved surgery residents' knowledge and self-efficacy in relation to pediatric trauma scenarios. METHODS: Participants attended training that included initial assessments of knowledge and self-efficacy, lecture, and practice with three trauma scenarios. After the training, residents completed pretest measures again. RESULTS: Findings indicated that resident knowledge and self-efficacy significantly increased afterthe simulation training. CONCLUSION: The current study suggests that for the adequate care of pediatric patients during trauma/emergency situations, high-fidelity simulation training may be beneficial. This may be particularly true for emergencies that are less frequent and not well practiced by clinicians and students. PMID- 22666977 TI - Intrahepatic cholestasis of pregnancy: a case report. PMID- 22666978 TI - Time out for surgeons: when is the attending surgeon too tired? AB - Pediatric surgical subspecialty workforce shortages are here to stay without any expected solution for the short-term. Individual surgeons, hospital administrators, risk management and patient-safety teams need to recognize that patient safety must take precedence over clinical productivity and financial "bottom lines." Pushing attending surgeon work hours beyond the limits of exhaustion impairs patient safety. Just as resident surgeon work hours have been appropriately curtailed in the name of patient safety, so must attending surgeon work hours. This issue needs to be addressed by hospital patient safety committees, professional societies, and by state and national regulating authorities. PMID- 22666979 TI - Accelerating the adoption of medical homes in Connecticut: a chronic-care support system modeled after public utilities. PMID- 22666980 TI - The president's page. 1962. PMID- 22666981 TI - Together we are stronger. PMID- 22666982 TI - Deus ex machina. PMID- 22666983 TI - Reviewing our history: economics, culture and healthcare reform. PMID- 22666984 TI - How the AMA benefits CSMS--and you. PMID- 22666985 TI - Punching holes in the arguments of politicians. PMID- 22666986 TI - NHS priorities. Mandate must set out a clear vision and reflect the reality. PMID- 22666987 TI - Poor patients face shorter GP opening hours. PMID- 22666988 TI - Bailouts cannot be used to hide F-failings. PMID- 22666989 TI - Give the public remote control. PMID- 22666990 TI - Thirty good men and true. PMID- 22666991 TI - Facilities management: Bringing it all back home. PMID- 22666992 TI - Staff-led redesign: Give them the power to do it differently. PMID- 22666993 TI - Innovation: Getting serious about greatness. PMID- 22666994 TI - VTE: From partnership to prevention. PMID- 22666995 TI - Nurses lead from where we stand: how can you impact the future of nursing? PMID- 22666996 TI - Evidence-based practice: the real future of nursing. PMID- 22666997 TI - Maintaining placement of temporary enteral feeding tubes in adults: a critical appraisal of the evidence. AB - Maintaining placement of temporary enteral feeding tubes requires ongoing bedside nursing assessment. Tube placement verification is essential to detect and minimize adverse effects. A critical appraisal of current evidence and best practice recommendations regarding temporary feeding tubes is provided. PMID- 22666998 TI - Comparison of pulse oximetry measures in a healthy population. AB - In this study finger and ear oximetry readings of 89 healthy persons were compared. The findings do not support the common nursing practice of using a finger sensor to obtain a pulse oximetry reading from an individual's ear if the finger is not usable. PMID- 22666999 TI - Preventing hospital-associated infection: MRSA. AB - By understanding the preventive strategies associated with reducing HA-MRSA transmission, the medical-surgical nurse can impact mortality rates and health care costs. He or she should model and enforce adherence to prevention strategies, such as hand hygiene, contact isolation, and other evidence-based strategies. PMID- 22667000 TI - Treating calcific aortic stenosis: an evolving science. AB - Calcific aortic stenosis is a common valvular disease, but its pathophysiology remains undetermined and important considerations exist for treatment. Pathophysiology, treatment by the advanced practice nurse, and literature review are discussed in the context of a case study. PMID- 22667001 TI - The lived experiences of a male survivor of intimate partner violence: a qualitative case study. AB - The purpose of this phenomenological qualitative case study, analyzed using Colaizzi's (1978) method, was to gain a holistic understanding of the lived experience of a male victim of intimate partner violence and the real-life context in which the violence emerged. PMID- 22667003 TI - Moving from a clinical question to research: the implementation of a safe patient handling program. PMID- 22667002 TI - Increasing testicular self-examination in active duty soldiers: an intervention study. AB - In this intervention study, the researchers assessed the knowledge of and health beliefs regarding testicular cancer and testicular self-examination (TSE) in active duty Army Soldiers. PMID- 22667004 TI - Block the bleed: pharmacologic therapies for gastroesophageal variceal bleeding. PMID- 22667005 TI - Applying the ethics of care to your nursing practice. PMID- 22667006 TI - Institute of Medicine The Future of Nursing Report, lifelong learning, and certification. PMID- 22667007 TI - Oral health literacy. PMID- 22667008 TI - Dental conundrum. PMID- 22667009 TI - What have I gotten myself into? PMID- 22667010 TI - Tech talk. PMID- 22667011 TI - How do dental and medical insurance influence oral and maxillofacial surgery in Pennsylvania? PMID- 22667012 TI - The uncertain future of health care in Pennsylvania. PMID- 22667014 TI - Realizing possibilities/enabling our client's occupations by examining our own. PMID- 22667013 TI - A view of dentistry in the Indian Health Service. PMID- 22667015 TI - Health equity, aboriginal peoples and occupational therapy. AB - BACKGROUND: In Canada, Aboriginal peoples are affected by colonial relations of power that result in poor health outcomes. Despite occupational therapists' efforts to work in a safe and competent manner with people experiencing challenges to participating in daily life, Western healthcare models reflect values that often undermine Aboriginal peoples' health and well-being. PURPOSE: Meaningful, effective, and culturally appropriate healthcare practices cannot be fully implemented by occupational therapists without an ongoing and critical examination of occupational therapy's foundational belief systems. Only a critical examination of these foundational belief systems will enable occupational therapists to take action towards addressing these inequities, which is an important step in moving towards culturally safe care. KEY ISSUES: Canadian health professions, including occupational therapy, have the potential to create positive change at a systems level through the critical exploration of underlying professional assumptions. IMPLICATIONS: To advance dialogue about Aboriginal peoples' health, occupational therapists must engage in exploration of their profession's underlying theoretical concepts or risk participating in the perpetuation of health inequities for already at-risk populations. PMID- 22667016 TI - Religious and/or spiritual practices: extending spiritual freedom to people with schizophrenia. AB - BACKGROUND: It continues to be a challenge to define and utilize spirituality in client-centred occupational therapy practice. Dialogue about spirituality is especially problematic for occupational therapists working with people with schizophrenia. PURPOSE: To explore the meaning of religion and/or spirituality for people living with a diagnosis of schizophrenia. METHODS: Nine community based individuals with schizophrenia engaged in interviews about the meaning of religion and/or spirituality and demonstrated self-defined spiritual practices. Phenomenology, hermeneutic theory, and a symbolic interactionism framework provided methodological and analytic guidance. FINDINGS: Participants employed religious and/or spiritual practices to cope with schizophrenia symptoms and make meaning of their lives. Individuals used multiple systems of meaning to explain their experiences. Religious and/or spiritual agency, an individual's sense of freedom to choose among the spiritual options, renewed their sense of empowerment. IMPLICATIONS: Therapists can engage in spiritual negotiation with clients by using well-worded empowering questions toward a common goal of life enhancement. PMID- 22667017 TI - Experiences of burnout and coping strategies utilized by occupational therapists. AB - BACKGROUND: Work-related stress and burnout have been found to lead to job dissatisfaction, low-organizational commitment, absenteeism, and high turnover. PURPOSE: The purpose of this study was to examine the burnout experiences of occupational therapists practicing in Ontario and to describe the practice implications and coping strategies employed. METHODS: Data for this mixed methods study were collected using the Maslach Burnout Inventory-General Survey, Areas of Worklife Survey, focus groups, and interviews in the hermeneutics tradition. FINDINGS: High levels of emotional exhaustion were reported by 34.8% of participants, high levels of cynicism by 43.5%, and low professional efficacy by 24.6%. Practice issues included excessive demands on time, conflict, and lack of autonomy and respect. Coping strategies included spending time with family and maintaining professional/personal balance, control of work responsibilities, maintaining a sense of humor, and self-awareness/self-monitoring. IMPLICATIONS: This study contributes to understanding the practice challenges for occupational therapists, factors that contribute to therapist burnout, and strategies employed to maintain competent practice. PMID- 22667018 TI - Evidence-based practice behaviours: a comparison amongst occupational therapy students and clinicians. AB - BACKGROUND: Occupational therapy graduates are expected to demonstrate entry level competencies in evidence-based practice. To support students during the course of professional education in developing the knowledge, skills, and attitudes for integrating scientific findings into clinical practice, educators must identify the process by which these competencies are developed. PURPOSE: To identify the differences in evidence-based practice decisions amongst occupational therapy students and experienced clinicians. METHODS: Using a vignette depicting an older client with a history of falls, participants' evidence-based practice decisions were compared to a reference model. RESULTS: In the initial steps of the process, knowledge of evidence-based practice concepts appeared to be dependent upon formal instruction, whereas expert-like behaviours in the integration of evidence for decision-making seemed to be a function of clinical experience. IMPLICATIONS: Academic and clinical educators can use identified gaps in knowledge and synthesis of concepts to update the evidence based practice content in occupational therapy curricula and fieldwork. PMID- 22667019 TI - [Issues surrounding the participation of auxiliary personnel in occupational therapy]. AB - BACKGROUND: With the current scarcity of occupational therapists, the idea of resorting to the use of support personnel in occupational therapy does not have consensus. In fact, occupational therapists are faced with service delivery options for which they are ill-informed. OBJECTIVE: To provide a synthesis of the Canadian and Quebec perspectives pertaining to the possibility for "skill mix" that is to say the participation of support personnel in occupational therapy, and to discuss ways in which they can participate. KEY ISSUES: "Skill mix" would allow an occupational therapist to delegate certain clinical activities to support personnel, so as to assert the full potential of occupational therapy. The Canadian Association of Occupational Therapists and l'Ordre des ergotherapeutes du Quebec recognize the contribution of support personnel and offer markers for the implementation of practices utilizing their services. IMPLICATIONS: This paper offers a critical reflection on this topic that is in need of further study. PMID- 22667020 TI - Administration of the Canadian Occupational Performance Measure: effect on practice. AB - BACKGROUND: The Canadian Occupational Performance Measure (COPM) is recommended as a systematic approach to identify issues and determine client progress in occupational therapy, yet little empirical evidence is available that supports this practice. PURPOSE: To determine if COPM administration was associated with changes in eight dimensions of occupational therapy practice. METHODS: Twenty four occupational therapists on eight geriatric rehabilitation sites completed a before-and-after study with a repeated baseline. The eight practice dimensions were assessed after three months of usual care (no COPM use) and after three months of intervention (COPM use) using chart stimulated recall (CSR) interviews and chart audit. FINDINGS: Mean practice scores for CSR interviews indicated a statistically significant practice improvement (p < .0001) across the eight dimensions, including knowledge of client perspective, clinical decision making, clinician ability to articulate outcomes, and documentation. Chart audit indicated that COPM use resulted in identifying more occupation-focused issues. IMPLICATIONS: COPM administration could improve occupational therapy practice. PMID- 22667021 TI - For better or worse. Report: where you live affects the type of healthcare you're going to get. AB - Geography is destiny when it comes to healthcare quality, according to the latest research from the Commonwealth Fund. Four of the best-performing communities are in Minnesota. "I'm not surprised at all that Minnesota cities did so well. There's a long history in this state of working as a community for the health of everyone," says Edward Ehlinger, left, commissioner of the Minnesota Department of Public Health. PMID- 22667022 TI - Law and politics. Determining ACA's legality not a typical case. PMID- 22667023 TI - Medicaid boost. Demo will expand pay for psychiatric hospitals. PMID- 22667024 TI - Too little, too late? First fine from HIPAA breach-notification rule not seen as much of a deterrent. PMID- 22667025 TI - Clock is ticking. Bills including Medicaid rate reduction head to Fla. governor's desk. PMID- 22667026 TI - 5,000-year-old problem. 'Tyrolean Iceman' makes a good argument in reform debate. PMID- 22667027 TI - Challenging assumptions. Improved healthcare requires re-examining long-held notions. PMID- 22667028 TI - Stay away. New reimbursement models strive to keep patients out of the hospital, with healthcare savings coming at a cost to providers. PMID- 22667029 TI - Blues man. Health plan executive Berman kept focus on the community. PMID- 22667030 TI - Hospital advocate. Davidson used teaching skills to advance hospitals' mission. PMID- 22667031 TI - I'll see you in court. For some hospital CEOs, the end of their employment is anything but amicable. PMID- 22667032 TI - Pushing the limit. Minnesota probe of Accretive's collection practices raises new questions on hospital billing policies. AB - The collection practices of hospitals once again grabbed the spotlight, with a report from Minnesota Attorney General Lori Swanson, left, that raises questions about aggressive techniques used by Accretive Health at Fairview Health Services in Minneapolis. While Fairview has already ended its contract with Accretive, a number of large systems still use the Chicago-based billing company. PMID- 22667033 TI - Cash for care. Annual Medicare payment reg focuses on quality. PMID- 22667034 TI - Pushing back. Proposed Medicare cuts to rural hospitals draw fire. PMID- 22667035 TI - Suboptimal care'. Report shows little improvement for minorities. PMID- 22667036 TI - McKesson settling up. $190 million payment latest in drug-price flap. PMID- 22667037 TI - Divide and conquer. Ambulatory group seeks to review hospitals. PMID- 22667038 TI - Stalled progress. EHR adoption lags for small, rural practices: studies. PMID- 22667039 TI - Jumping hurdles. Some AHRQ grant ideas moving ahead. PMID- 22667040 TI - Avoiding the plunge. Looming fiscal deadlines pose challenges for healthcare, nation. PMID- 22667041 TI - Meeting critical needs. 'Legacy physicians,' facing workforce issues key to reshaping emergency care. PMID- 22667042 TI - Rewards and their risks. More hospitals offer frontline incentive programs to complement the push for value-based purchasing, but some see pitfalls. PMID- 22667043 TI - The price of prevention. Providers find CDC's tracking system for HAIs valuable but burdensome. PMID- 22667044 TI - Inside the racist mind: bias is the complex neural interplay between emotions and beliefs. PMID- 22667045 TI - [Neurologic complications in cardiac surgery patients]. AB - Cerebral infarction and hypoxic-ischemic brain damage (HIE) may impair the recovery of a patient from otherwise successful cardiac operation. Severe neurologic complications occur in approximately 2 to 5% of cardiac surgery patients. The major risk factors can be recognized. The most common cause of cerebral infarction is a calcific embolus released during manipulation of atheromatotic aorta. HIE results from cerebral circulatory deficiency and subsequent hypoxia in the cerebral tissue. The development of complications can be prevented by restricting aortic manipulation and by optimizing the perfusion technique and other treatment during the operation. PMID- 22667046 TI - [Genetic testing of patients with cardiomyopathies, the resuscitated and victims of sudden death--new international expert recommendations]. AB - Recent international expert group recommendations for gene tests of myocardial or conducting system diseases as well as those concerning molecular genetic investigations of persons resuscitated after cardiac arrest or victims of sudden death are summarized. Systematic examination of an index patient forms the basis for correct clinical diagnosis and is a prerequisite for successful genetic testing. The first-degree relatives of victims of unexplained sudden death should be referred to clinical assessment due to the possibility of an inherited heart disease. Genetic testing of sudden death victims should be performed more frequently than previously, but targeting of the tests must be done on the basis of clinical data. PMID- 22667047 TI - [When gluten-free diet does not cure celiac disease]. AB - Dietary deviations and continuous usage of gluten even in small amounts are the most common causes of poor treatment response for celiac disease. In rare refractory celiac disease symptoms and small bowel mucosal morphological damage do not heal despite a strict diet. In such cases it is important to distinguish between type I and II refractory celiac disease by using small bowel lymphocyte markers and clonality of inflammatory cells. Increased risk of small intestinal lymphoma is especially associated with type II disease, which has a poorer prognosis. Type I is often treated with corticosteroids and azathioprine. PMID- 22667048 TI - [Histamine intolerance and pseudoallergy--do they exist?]. AB - Histamine intolerance (HIT) is a controversial syndrome, in which the body is believed to react to histamine released by certain foodstuffs. Symptoms include among other things headache, urticaria and abdominal discomfort. Several fruits, nuts, spices and food additives have been regarded as pseudoallergens. Since there is no objective investigation to prove HIT, the diagnosis is based on symptoms. On the basis of literature, better clinical studies are needed. Because the phenomenon remains unclear, use of the terms histamine intolerance and pseudoallergens is not recommended. PMID- 22667049 TI - [Complications of acute otitis media]. AB - Most cases of acute otitis media (AOM) resolve even without antibiotic treatment. In the pre-antibiotic era, AOM complications were common and could lead to deafness and neurological sequelae. With the use of antibiotics, the complications have become less frequent, but they may still evolve. The possible increase in the occurrence of complications has to be considered if we start treating AOM more conservatively and if bacterial antibiotic resistance situation becomes more problematic. These rare but possibly lethal complications should be diagnosed and treated promptly. The need for cochlear implantation has to be evaluated soon after an episode of meningitis if deafness is suspected. PMID- 22667050 TI - [How do I distinguish migraine aura from TIA attack?]. AB - Migraine aura is almost always a visual disturbance involving "positive" (rippling, stars) and "negative" (visual field defect) phenomena. It expands and gradually vanishes within 5 to 60 minutes. Evolution of symptoms and positivity are typical for migraine. TIA appears more abruptly and is usually of shorter duration. Negativity is typical for it, i.e. part of the visual field, speech, eye movement, ability to swallow, sensation or muscle strength disappear without the above mentioned features of migraine. In migraine, aura is usually followed by headache, whereas in TIA headache is less frequent. PMID- 22667051 TI - [Successful hypnotherapy in an intellectually disabled patient with drug treatment resistant epilepsy]. AB - The possibility of psychogenic non-epileptic seizures (PNES) should be considered in patients with treatment-resistant epilepsy for whom hypnotherapeutic approach may be tried as one treatment option. Multimodal epileptic seizures as well as various behavioral and dyskinetic disorders are commonly associated with intellectual disabilities. Differentiation of brain derived epileptic seizures from other non-epileptic seizures requires an extensive anamnesis, clinical follow-up of the patient and video-EEG recording of seizures. We describe a patient with mild intellectual disability whose almost daily, drug-resistant epileptic attacks were found to be psychogenic. Hypnotherapeutic relaxation initiated upon mother's suggestion turned out to be useful. PMID- 22667052 TI - [Sudden drop out of school due to psychic stress after repeated urinary tract surgery]. AB - A 15-year old boy dropped out of school, withdrew into his home and, on inquiry upon the matter, threatened with suicide. Upon disentangling the issue it turned out that the boy perceived his urinary tract disease and associated pediatric surgery procedures so shameful and distressing that they had eventually exceeded his psychic ability. The mental state of the boy improved with therapeutic discussions and adolescent psychiatric rehabilitation. PMID- 22667053 TI - [Update on current care guidelines: melanoma]. AB - This updated guideline focuses on the diagnosis and treatment of cutaneous melanoma. Diagnosis is based on the excision and histopathological analysis of a suspected skin lesion. Definitive surgery should be performed by an experienced surgical unit. Sentinel node biopsy is standard care in the case of clinically nodal-negative patients with intermediate-thickness or thick melanomas. Complete lymph node dissection is performed selectively in the case of sentinel-positive patients. Adjuvant therapy with interferon-alpha can be considered in high-risk patients. The follow-up schedule of an asymptomatic patient can be based on histopathological and clinical prognostic factors. PMID- 22667054 TI - The Joint Commission and NQF honor 2011 Eisenberg Award recipients. Annual award recognizes excellence in safety and quality of care. PMID- 22667055 TI - The Joint Commission continues to study overuse issues. PMID- 22667056 TI - Sentinel events statistics for 2011. PMID- 22667057 TI - Managing door maintenance. PMID- 22667058 TI - Dangerous connections. Health care community tackles tubing risks, small-bore connector standards. PMID- 22667059 TI - The truth, the whole truth, and nothing but the truth. PMID- 22667060 TI - The KPG index--a novel 3D classification system for maxillary canine impactions. AB - INTRODUCTION: Advancements in Cone Beam Computed Tomography (CBCT) have improved localization of impacted canines. The KPG index is the first 3-D classification system for classifying the position of canines based on their distance from the norm (1). The aim of this study was to determine if this index provides an estimate of the time necessary to treat an impacted canine using closed eruption. MATERIALS AND METHODS: CBCT scans of 28 impacted canines at The University of Texas School of Dentistry at Houston Department of Orthodontics were classified using the KPG index. The scores and categories were compared to the time from surgical exposure to proper positioning. RESULTS: Four canines were classified as "Easy," 11 as "Moderate," 9 as "Difficult," and 4 as "Extremely Difficult." Average treatment times associated in months were: "Easy"--11.23, "Moderate"- 11.36, "Difficult"--12.76, and "Extremely Difficult"--13.23. CONCLUSIONS: The KPG index currently cannot be confirmed as an accurate means of estimating treatment time for an impacted canine. Further verification studies should include larger sample sizes and compare differing mechanics. However, there are limitations to 2 D imaging; therefore, the 3-D CBCT images and the KPG index, with further validation, will become increasingly valuable to orthodontists. PMID- 22667061 TI - Calibration of equipment for analysis of drinking water fluoride: a comparison study. AB - Current American Dental Association evidence-based recommendations for prescription of dietary fluoride supplements are based in part on the fluoride concentration of a pediatric patient's drinking water. With these recommendations in mind, this study compared the relative accuracy of fluoride concentration analysis when a common apparatus is calibrated with different combinations of standard values. Fluoride solutions in increments of 0.1 ppm, from a range of 0.1 to 1.0 ppm fluoride, as well as 2.0 and 4.0 ppm, were gravimetrically prepared and fluoride concentration measured in pentad, using a fluoride ion-specific electrode and millivolt meter. Fluoride concentrations of these solutions were recorded after calibration with the following 3 different combinations of standard fluoride solutions: 0.1 ppm and 0.5 ppm, 0.1 ppm and 1.0 ppm, 0.5 ppm and 1.0 ppm. Statistical analysis showed significant differences in the fluoride content of water samples obtained with different two-standard fluoride solutions. Among the two-standard fluoride solutions tested, using 0.5 ppm and 1.0 ppm as two-standard fluoride solutions provided the most accurate fluoride measurement of water samples containing fluoride in the range of 0.1 ppm to 4.0 ppm. This information should be valuable to dental clinics or laboratories in fluoride analysis of drinking water samples. PMID- 22667062 TI - Resin modified glass ionomer restorations placed in non-carious cervical lesions have similar if not better retention rates than resin composites (UT CAT #628). PMID- 22667063 TI - Cone beam computed tomography imaging in the evaluation of the temporomandibular joint. AB - A radiological examination is an essential part of the diagnosis and management of temporomandibular joint disease. Accurate evaluation of the TMJ has been difficult due to the superimposition of other structure in convention radio graphs. Cone beam computed tomography provides precise imaging of TMJ anatomy without superimposition and distortion. The CBCT's preciseness enables practitioners to better identify problems, as well for other strategies. Common conditions of the TMJ in which CBCT plays a role are discussed. PMID- 22667064 TI - Case of the month. Peripheral odontogenic keratocyst. PMID- 22667065 TI - Planning for esthetics--Part II: Adjacent implant restorations. PMID- 22667066 TI - Why your office should be texting. PMID- 22667067 TI - "Nurses aren't immune to changes in etiquette". PMID- 22667068 TI - DH unveils regional pay ambitions. PMID- 22667069 TI - "Give sisters the freedom to be ward leaders and innovators". PMID- 22667070 TI - "Finding nurses who will speak out is like hunting for Easter eggs". PMID- 22667071 TI - "Simple actions can help a lot at incredibly difficult times". PMID- 22667072 TI - How to care for people with Parkinson's disease. AB - Parkinson's disease is a complex and debilitating neurological condition that requires nursing care that is tailored to the individual. This article provides an overview of the condition, discusses the role of Parkinson's specialist nurses and gives advice on care. PMID- 22667073 TI - I know what my body is telling me I need. PMID- 22667074 TI - How enhanced recovery can boost patient outcomes. AB - The enhanced recovery approach aims to optimise patient outcomes and improve their experience. This article outlines its key principles and describes its benefits. PMID- 22667075 TI - Using a big conversation to improve care quality. AB - The Collaboration for Leadership in Applied Health Research and Care (CLAHRC) compiled a report on the day, in which it noted: "The overriding result was one of inspiration through being heard, having honest, genuine and open dialogue and positively engaging with like-minded people. The event gave many the confidence to try to take things forward and influence others, and there was a sense of the event being an opportunity that gave hope for the future." The next step is to set up a "nursing cabinet"--a stakeholder board that will oversee work to improve "care through the patients' eyes". This will involve health professionals, academics, voluntary organisations and patient groups. Box 1 outlines key actions taken as a result of the event. The report on the day's findings is available on the trust website. PMID- 22667076 TI - Learning the lessons of moving education online. AB - Education providers across the world are transferring course delivery from face to-face to online methods. This article reports on a New Zealand college's experience of transferring a course on nursing research to online delivery, and on an evaluation of the initiative from the perspective of student experiences and achievements. The results and discussion contain lessons for any education providers considering moving courses to online delivery. PMID- 22667077 TI - 60 seconds with Kerri Wright. PMID- 22667078 TI - Urgent care in the Arctic. PMID- 22667079 TI - Ensure care and advice is based on evidence. PMID- 22667080 TI - The man who remade motherhood. PMID- 22667081 TI - The detached dad's manifesto. How fathers can contribute by just chilling out. PMID- 22667082 TI - [Mixed-mode chromatography of biopolymers--traditional concept of liquid chromatography being changed]. PMID- 22667083 TI - [New technique for nanoparticle capillary electrophoresis/microfluidic chip and its uses in enantioselective separation]. AB - Nanoparticles have been widely used in separation science due to their large specific surface area and good biocompatibility. Nanoparticle capillary electrophoresis (CE)/microfluidic chip (MC) technique is the hybrid of nanomaterial and the CE/MC technique. By being adsorbed or bonded onto the inner surface of the capillary, the nanoparticles can interact with the analytes as stationary phase. As a kind of separation medium, the nanoparticles can also participate in the separation process acting as a pseudostationary phase (PSP) to improve the separation efficiency and selectivity. Chirality is one of the intrinsic characters of the nature. It is important to develop the novel, fast, highly efficient and sensitive chiral separation technique in many research areas, such as stereoselective synthesis of enantiomers, pharmacology, chiral compounds purity check and environment monitoring. Herein, the recent applications of different types of nanoparticles such as polymer nanoparticles, magnetic nanoparticles, gold nanoparticles and carbon nanotubes in enantioseparation by CE/MC are reviewed, and the future developments in this area are also prospected. PMID- 22667084 TI - [Exploring the mechanism of rhizoma coptidis in treating type II diabetes mellitus based on metabolomics by gas chromatography-mass spectrometry]. AB - Metabolomics was used to explore the mechanism of Rhizoma coptidis in treating type II diabetes mellitus. The rat model of type II diabetes mellitus was constructed by an injection of streptozocin (40 mg/kg), along with diets of fat emulsion. The rats were divided into four groups, the control group, the model group, the Rhizoma coptidis group (10 g/kg) and the metformin group (0.08 g/kg). After the treatment for 30 d, blood samples were collected to test biomedical indexes, and 24 h urine samples were collected for the metabolomics experiment. In the Rhizoma coptidis group, fasting blood glucose (FBG), total cholesterol (TC) and total plasma triglycerides (TG) were significantly decreased by 59.26%, 58.66% and 42.18%, respectively, compared with those in the model group. Based on gas chromatography-mass spectrometry, a urinary metabolomics method was used to study the mechanism of Rhizoma coptidis in treating diabetes mellitus. Based on the principal component analysis, it was found that the model group and control group were separated into two different clusters. The Rhizoma coptidis group was located between the model group and the control group, closer to the control group. Twelve significantly changed metabolites of diabetes mellitus were detected and identified, including 4-methyl phenol, benzoic acid, aminomalonic acid, and so on. After diabetic rats were administered with Rhizoma coptidis, 7 metabolites were significantly changed, and L-ascorbic acid and aminomalonic acid which related with the oxidative stress were significantly regulated to normal. The pharmacological results showed that Rhizoma coptidis could display anti hyperglycemic and anti-hyperlipidemic effects. The Rhizoma coptidis had antioxidation function in preventing the occurrence of complications with diabetes mellitus to some extent. The work illustrates that the metabolomics method is a useful tool to study the treatment mechanism of traditional Chinese medicine. PMID- 22667085 TI - [Determination of seven toxaphene congeners in ginseng and milkvetch root by gas chromatography tandem mass spectrometry]. AB - A novel method for the determination of representative toxaphene congeners in traditional Chinese herbal medicines was developed. Ginseng and Milkvetch Root were selected as the samples and seven toxaphene congeners were selected as the monitoring objects. The samples were extracted by accelerated solvent extraction with cyclohexane-acetone (9:1, v/v), then cleaned-up by Florisil solid phase extraction with hexane as the eluent and the residues were detected by gas chromatography-electron ionization tandem mass spectrometry (GC-EI-MS/MS) in multiple reaction monitoring (MRM) mode. The performance was demonstrated by the analysis of Ginseng and Milkvetch Root samples spiked with toxaphene congeners at three concentration levels of 0.005, 0.01 and 0.1 mg/kg. The recoveries ranged from 72.4% to 105% with the relative standard deviations (RSDs) of 0.96%-10.4%. The limits of detection (LODs) were 0.2-1.7 microg/kg. This method is sensitive and efficient in the aspect of extraction, and can be applied to monitor the residue of toxaphene congeners in Ginseng and Milkvetch Root. PMID- 22667086 TI - [Determination of 9 residual acrylic monomers in acrylic resins by gas chromatography-mass spectrometry coupled with microwave assisted extraction]. AB - A reliable gas chromatography-mass spectrometry (GC-MS) method was developed for the determination of 9 residual acrylic monomers (methyl acrylate, ethyl acrylate, methyl methacrylate, ethyl methacrylate, n-butyl acrylate, butyl methacrylate, styrene, acrylic acid and methacrylic acid) in acrylic resins. Solid resin was precipitated with methanol after microwave assisted extraction with ethyl acetate for 30 min, and liquid resin was diluted with methanol directly. The nine acrylic monomers got a good separation within 20 min on a DB WAX column. The limits of quantification (LOQs, S/N = 10) of the method were in the range of 1-10 mg/kg for liquid resin and 3-50 mg/kg for solid resin. The calibration curves were linear within 1-500 mg/L range with correlation coefficients above 0. 995. The recoveries ranged from 84.4% to 108.6% at five spiked levels. The sensitivity, recovery and selectivity of the method can fully meet the requirements of practical work. PMID- 22667087 TI - [Determination of 23 phthalate esters in food by solid-phase extraction coupled with gas chromatography-mass spectrometry]. AB - A method for the simultaneous determination of 23 phthalate esters in food samples by solid-phase extraction coupled with gas chromatography-mass spectrometry (SPE-GC-MS) was developed and evaluated. The samples were extracted with hexane or acetonitrile, and cleaned up with a glass ProElut PSA SPE column. The identification and quantification were performed by GC-MS in selected ion monitoring (SIM) mode. The extraction processes of different foods were investigated. The calibration curves of phthalate esters showed good linearity in the range of 0.05-5 mg/L (0.5-5 mg/L for diisononyl phthalate (DINP), diisodecyl phthalate (DIDP)) with the correlation coefficients (r) between 0.984 8 and 0.999 6. The limits of detection of phthalate esters in food samples ranged from 0.005 to 0.05 mg/kg (S/N = 3) and the limits of quantification ranged from 0.02 to 0.2 mg/kg (S/N = 10). The average recoveries of 23 analytes spiked in 10 kinds of food matrices ranged from 77% to 112% with the relative standard deviations (RSDs, n = 6) of 4.1%-12.5%. The method is suitable for the determination of 23 phthalate esters simultaneously in foodstuffs with easy operation, high accuracy and precision. PMID- 22667088 TI - [Determination of streptomycin and dihydrostreptomycin residues in tomato paste by tandem dual solid phase extraction column-liquid chromatography-tandem mass spectrometry]. AB - The method was specifically developed for the simultaneous determination of streptomycin and dihydrostreptomycin residues in tomato paste by tandem dual solid phase extraction (SPE) column cleanup-liquid chromatography-tandem mass spectrometry. The residues were extracted from the samples with phosphate buffer solution (pH 4). The cleanup was performed by the way of dispersive solid phase extraction and tandem dual solid phase extraction column. The polar chromatographic column was used to complete the separation of the analytes under gradient elution and the analytes were detected in multiple reaction monitoring (MRM) mode via positive electrospray ionization (ESI +). The external standard calibration curves were used for the quantification. The linear ranges were from 0.01 to 0.2 mg/L with a good linear relationship (r > 0.999) for streptomycin and dihydrostreptomycin. The limit of quantification (LOQs) was 0.02 mg/kg for the both analytes. The recovery range was from 71% to 101% with the relative standard deviations (RSDs) between 2.3% and 15%. It was indicated that this method is accurate, easier, more sensitive, and has a better purification effect in the monitoring and analysis. The method is accurate and specific to monitor and analyze of streptomycin and dihydrostreptomycin residues in tomato paste and its products. PMID- 22667089 TI - [Determination of glyphosate and aminomethylphosphonic acid in rice using hydrophilic interaction chromatography-tandem mass spectrometry]. AB - A method was developed for the simultaneous determination of glyphosate (Gly) and aminomethylphosphonic acid (AMPA) residues in rice using hydrophilic interaction chromatography-tandem mass spectrometry (HILIC-MS/MS). The samples were extracted with water, and purified using a C18 solid phase extraction cartridge followed by an ultrafiltration membrane to remove interfering materials. Gly and AMPA were separated on an HILIC column with the mobile phases of 1 mmol/L ammonium acetate (pH 11.0 adjusted with ammonium hydroxide) and acetonitrile, and finally detected with negative electrospray ionization (ESI-) in multiple reaction monitoring (MRM) mode. The matrix-matched external standard calibration curves were used for quantitative analysis. The sample pretreatment of Gly and its metabolite was successfully carried out without any derivatization. Under the optimal analytical conditions, the linearities of Gly and AMPA were in the concentration ranges of 0. 001 to 0. 250 mg/L and 0. 002 5 to 0. 250 mg/L respectively, with the correlation coefficients of 0. 999 5 for the both analytes. The limits of detection (S/N = 3) of the method were 0.010 mg/kg for Gly, and 0.020 mg/kg for AMPA. For all the samples, the mean spiked recoveries of Gly and AMPA were in the range from 96.3% to 107.3% at 3 spiked levels (0.100, 0.500 and 2.500 mg/kg), and the relative standard deviations (RSDs, n = 3) were in the range of 1.3%-9.1%. The method is easy, fast, sensitive and accurate, and can meet the requirements of the determination of Gly and AMPA pesticide residues in rice. PMID- 22667090 TI - [Determination of 3-methyl-quinoxaline-2-carboxylic acid in animal and aquatic products by ultra performance liquid chromatography-tandem mass spectrometry]. AB - An ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/ MS) method was established for the determination of 3-methyl-quinoxaline-2-carboxylic acid (MQCA) in animal tissues and aquatic products. The analyte was extracted with 0.2 mol/L hydrochloric acid. The extract was cleaned up on a Bond Elut C18 cartridge. Then the eluate was collected and evaporated to dryness under nitrogen gas at 35 degrees C. The residue was redissolved in acetonitrile containing 0.1% (v/v) formic acid. The identification was performed by multiple reaction monitoring in positive electrospray ionization. The quantification was done by external standard method. The calibration curves showed good linearity within the range of 2-500 microg/L with the correlation coefficients (r2) greater than 0.990. The limits of detection (LODs) of MQCA in pork, swine liver, pig kidney, fish, prawn, and crab were 0.90, 1.51, 0.94, 1.04, 1.62 and 1.80 microg/kg, respectively; and the limits of quantification (LOQs) were 3.00, 5.02, 3.13, 3.46, 5.40 and 6.00 microg/kg, correspondingly. The recoveries of MQCA in animal tissues and aquatic products were 73.6%-89.0% at the spiked levels of 3-100 microg/kg. The intra-day relative standard deviations (RSDs, n = 5) were less than 15%, and inter-day RSDs (n = 3) were less than 20%. The results demonstrated that the sensitivity, accuracy, and precision were fit for the requirements of veterinary drug residue analysis. PMID- 22667091 TI - [Simultaneous determination of nine microcystins in surface water by solid phase extraction and ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry]. AB - A method has been developed for the simultaneous determination of nine microcystins (MCs) in surface water by solid phase extraction-ultra performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (SPE-UPLC-ESI-MS/MS). The samples were enriched and purified by an HLB solid phase extraction column. The separation was performed on an ACQUITY UPLC system with a BEH C18 column with the gradient elution of acidified acetonitrile and water (both containing 0.1% (v/v) formic acid). The nine MCs were determined in the modes of electrospray positive ionization (ESI+) and multiple reaction monitoring (MRM). Good linearities were observed in the ranges of 0.1-50 microg/L for MC-RR and 0.5-100 microg/L for the others with correlation coefficients over 0. 999 0 and the limits of detection for the nine MCs were in the range of 0.1-0.5 ng/L. The recoveries were in the range of 75.8%-109% in the three spiked levels of 1.0, 10 and 50 microg/L with the relative standard deviations of 0.49%-10.0%. The method is characterized by high sensitivity and precision, extensive analytical range and quick analytical rate. This method was used in the analysis of water samples from two reservoirs situated in Hangzhou, and the 3 and 8 microcystins were detected individually. PMID- 22667092 TI - [Molecularly-imprinted solid phase extraction coupled with high performance liquid chromatography for the determination of ractopamine in feed samples]. AB - Molecularly imprinted polymers (MIPs) with high selectivity to ractopamine (RAC) were prepared by using RAC as template, acrylamide (AM) as monomer, and ethylene glycol dimethacrylate (EGDMA) as cross-linker. The effects of four porogens (methanol, acetonitrile, acetone, and chloroform-methanol) with triethylamine (30:1, v/v) on the recognition capability of MIPs to RAC and the morphological characteristics of the polymers were investigated. Orthogonal test was used to optimize the preparation of MIPs, and the optimal compositions were as follows: 1.0 mmol RAC, 4.0 mmol AM, 20.0 mmol EGDMA, 6.0 mL acetonitrile-triethylamine (30:1, v/v), and 50.0 mg azobisisobutyronitrile. A high performance liquid chromatographic method based on molecularly-imprinted solid-phase extraction (MISPE) was developed for the determination of ractopamine in feed samples. The limit of detection (LOD, S/N = 3) of ractopamine was 0.1 mg/kg. The linear range was 0.50-100 mg/L (r = 0.999 4). Mean recoveries of RAC spiked in 3 kinds of feed samples at 1.0, 10 and 100 mg/kg were above 80% with the relative standard deviations of less than 10%. The clean-up efficiency of MISPE was ideal for feed samples. The method is more sensitive and reproduciable than the standard analytical method for the determination of RAC in feed matrices. PMID- 22667093 TI - [Simultaneous determination of organic acids and saccharides in lactic acid fermentation broth from biomass using high performance liquid chromatography]. AB - Abstract: A high performance liquid chromatographic method for the simultaneous determination of organic acids and saccharides in lactic acid fermentation broth from biomass was developed. A Bio-Rad Aminex HPX-87H column was used at 55 degrees C. The mobile phase was 5 mmol/L sulfuric acid solution at a flow rate of 0.6 mL/min. The samples were detected by a refractive index detector (RID). The results showed that six organic acids and three saccharides in fermentation broth were completely separated and determined in 17 min. The linear correlation coefficients were above 0.999 8 in the range of 0.15-5.19 g/L. Under the optimized conditions, the recoveries of the organic acids and saccharides in Rhizopus oryzae fermentation broth at two spiked levels were in the range of 96.91%-103.11% with the relative standard deviations (RSDs, n = 6) of 0.81% 4.61%. This method is fast and accurate for the quantitative analysis of the organic acids and saccharides in microbial fermentation broths. PMID- 22667094 TI - [Preparation of immunoaffinity chromatographic column specific to diniconazole and its applications to the pretreatment of samples]. AB - The purified anti-diniconazole antibody was polymerised to hydrolytic tetramethoxysilane (TMOS) to synthesize the immunosorbent for the immunoaffinity chromatographic (IAC) column specific to diniconazole. The optimized conditions of the IAC were as follows: water as equilibrium and adsorbent medium, 30% and 50% (v/v) methanol aqueous solutions as eluents. The results showed that the dynamic column capacity was up to 125.4 microg/g of bed volume. The river water and fruit samples spiked with diniconazole were cleaned up and enriched by the IAC, and the diniconazole in eluant was determined by high performance liquid chromatography. The average recoveries (n = 5) of diniconazole in river water sample were 90.36%-100.14% with relative standard deviations (RSDs) of 2.03% 6.08%, and the average recoveries in fruit samples were 85.55%-94.02% with RSDs of 3.38%-6.78%. The IAC cleanup procedure provided an effective pretreatment method for the determination of diniconazole in sample media such as river water and fruits. PMID- 22667095 TI - [Simultaneous determination of bensulfuron-methyl and mefenacet residues in paddy field using high performance liquid chromatography]. AB - An analytical method of high performance liquid chromatography (HPLC) was established for the simultaneous determination of bensulfuron-methyl and mefenacet residues in paddy field (paddy water, soil and rice plant). The residues in the paddy water was extracted with methylene chloride, and the soil with alkaline mixed solution of acetonitrile-methylene chloride (1:1, v/v). The rice plant was extracted with alkaline methylene chloride which was cleaned up by a Florisil column. The separation was performed on a stainless steel C18 column (150 mm x 4.6 mm, 5 microm) at 30 degrees C by HPLC with an ultraviolet detector (UVD) at 238 nm, and water-methanol (30:70, v/v) as the mobile phase at a flow rate of 0.5 mL/min. The quantification was performed by external standard. The calibration curves were linear between the peak area and the concentration in the range of 0.05-5.00 mg/L for bensulfuron-methyl and mefenacet, and the correlation coefficients were more than 0.999 9. The average recoveries of the two herbicides spiked in the paddy water, soil and rice plant at the three concentration levels of 0.05, 0.10 and 1.00 mg/kg ranged from 85.39% to 113.33% with the relative standard deviations of 0.91%-10.24%. The method is characterized by simplicity, sensitivity and accuracy. PMID- 22667096 TI - [Determination of trace perchlorate in groundwater by solid phase extraction-ion chromatography]. AB - A comprehensive analytical method based on solid phase extraction-ion chromatography (SPE-IC) has been developed for the determination of trace perchlorate in groundwater. An amount of 0.7 liter of groundwater was enriched by a solid phase extraction column after pretreatment to remove the interference ions and then the column was eluted by 6 mL 1% NaOH solution. After filtration of the concentrated liquor with a filter membrane (0.45 microm), the liquor was analyzed on an ion chromatograph (IC) equipped with an Ion Pac AS20 separation column and a 50 microL injection loop, eluted with 40 mmol/L KOH solution. The method detection limit (MDL) and limit of determination (LOD) of perchlorate were 0.15 microg/L and 0.60 microg/L, respectively. The recovery was in the range of 99.7%-100.5% when the sampling concentrations were in the range of 1-15 microg/L. The method is economical and effective. It can be applied to determine trace perchlorate in groundwater. The perchlorate in groundwater samples got from the areas surrounding Harbin was determined by this method. The relative errors were in the range of 1.85%-9.24% between the results got by the SPE-IC and ion chromatography-tandem single quadrupole mass spectrometry. PMID- 22667097 TI - [Preparation of immunoglobulin from chicken egg yolk by anion-exchange chromatography]. AB - An economical, effective and large-scale method for the preparation of immunoglobulin of chicken egg yolk (IgY) was developed. The method was based on an improved water dilution combining with polyethylene glycol 6000 (PEG6000) precipitation and anion-exchange chromatography. The egg yolk was diluted with 8 volumes of aseptic water, the pH of which was adjusted to 5.2 with 0.1 mol/L HCl, then the mixture was centrifuged at 5 000 x g after standing for 8 h at 4 degrees C. The crude IgY was obtained from the supernatant layer with the yield of 93.47%. The purification of IgY was achieved by 6% PEG6000 precipitation and DEAE Toyo-pearl 650 M anion-exchange chromatographic packing. The optimum purified conditions by ion-exchange chromatography were as follows: equilibration with 0.05 mol/L phosphate buffer (pH 7.0) and elution with 0. 075 mol/L phosphate buffer (pH 7.0). The purity of the IgY fraction was consistently greater than 95% with high activity (73.77%) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). This method is superior to the traditional ion exchange chromatography that can't simultaneously obtain high purity and high recovery. Moreover, this method is suitable for a large-scale IgY preparation from chicken egg yolk. PMID- 22667098 TI - [Preparation and characterization of recombinant protein A affinity packing]. AB - To obtain an excellent antibody purification medium, affinity chromatographic packing with recombinant staphylococcal protein A (rProtein A) was synthesized and verified. With E. coli cells harboring the recombinant plasmid, the rProtein A was expressed and purified, then was conjugated to epichlorohydrin-activated Sepharose 4 Fast Flow to prepare an affinity chromatographic packing. The performances of the packing were validated with rabbit antiurate oxidase. After the reaction, the concentration of rProtein A coupled to Sepharose 4 Fast Flow was 1.5 x 10(-4) mol/L. Scatchard analysis of the binding isotherm for IgG showed excellent binding capacity on the adsorbent, giving a dissociation constant (Kd) of 2.28 x 10(-7) mol/L and a theoretical maximum adsorption capacity of 20. 697 g/L. The identification showed the packing was stable in 0.1 mol/L NaOH solution at 1 h. By using the packing, the pure antibody exhibited on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was obtained from rabbit serum after one-step elution, with 96. 1% of yield and 19 mg IgG for one milliliter of gel. The research laid the foundation of the localization of rProtein A affinity packing. PMID- 22667099 TI - [Determination of thiophanate-methyl and carbendazim in cucumber and soil by QuEChERS-high performance liquid chromatography-triple quadrupole tandem mass spectrometry]. AB - A method was developed for the determination of thiophanate-methyl and carbendazim residues in cucumber and soil by using QuEChERS-high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). The residues in the samples were extracted by acetonitrile, cleaned up by developed QuEChERS method, and then analyzed by using LC-MS/MS in multiple reaction monitoring (MRM) mode via positive electrospray ionization with an Agilent ZORBAX SB-C, column (30 mm x 2.1 mm, 5 microm) as the analytical column. The recoveries of thiophanate-methyl spiked at four levels of 0.01, 0.05, 0.1 and 1.0 mg/kg were from 87.3% to 96.0% with the relative standard deviations (RSDs) of 8.0%-9.3% in cucumber, from 88.8% to 93.4% with the RSDs of 5.3%-9.9% in soil; the recoveries of carbendazim spiked at the same levels as those of thiophanate-methyl were from 87.1% to 92.3% with the RSDs of 5.2%-7.5% in cucumber, from 85.8% to 90.9% with the RSDs of 5.3%-13.2% in soil. The method is simple, rapid and characterized with acceptable sensitivity and accuracy to meet the requirements of the pesticide residue analysis. This method is applicable to confirm the residues of thiophanate-methyl and carbendazim PMID- 22667100 TI - [Determination of bisphenol A in plastic parts of small household appliances by liquid chromatography-tandem mass spectrometry]. AB - A method for the determination of bisphenol A in the plastic parts of small household appliances by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed. The sample was extracted with accelerated solvent extraction (ASE) and purified by Sep-Pak C18 solid phase extraction. Bisphenol A was separated and detected using LC-MS/MS in negative ion mode with the mobile phases of methanol and water (containing 0.05% ammonia water). The linearity of the method was good in the range of 5 MUg/L to 100 MUg/L. The recoveries for the spiked sample were from 95.2% to 109.7% at the three levels, 10, 25 and 75 MUg/kg. The relative standard deviations were less than 3.8%. The limit of detection was 10 MUg/kg. The method is easy-handling, time-saving, sensitive and suitable for the determination of the residual bisphenol A in the plastic parts of household appliances. PMID- 22667101 TI - [Determination of residual organic solvents in flunixin meglumine raw material by headspace gas chromatography]. AB - A method for the determination of five kinds of residual organic solvents in flunixin meglumine raw material was developed by headspace gas chromatography. An HP-FFAP capillary column (30 m x 0.32 mm x 1.0 microm), a flame ionization detector and the external standard method were used for the separation and quantitative analysis. The effects of equilibrium temperature and equilibrium time on the determination of residual organic solvents were investigated. The good results were obtained in the equilibrium temperature of 90 degrees C and equilibrium time of 30 min. The standard curves were linear in the range of 0.40 7.93 mg/L (r = 0.999 8) for ethyl acetate, 7.32-146.48 mg/L (r = 0.999 6) for methanol, 4.53-90.61 mg/L (r = 0.999 9) for isopropanol, 3.62-72.32 mg/L (r = 0.999 8) for ethanol and 2.31-46.24 mg/L (r = 0.999 6) for acetonitrile. The recoveries for the five residual organic solvents were between 95.96% and 100.31% with relative standard deviations (RSDs) (n = 6) of 1.97%-3.28%. The detection limits of ethyl acetate, methanol, isopropanol, ethanol and acetonitrile were 0.08, 0.9, 0.2, 0.4 and 0.3 mg/L, respectively. The proposed method was successfully applied to analyze the residual organic solvents in the real sample of flunixin meglumine raw material. The results showed that only isopropanol and ethanol were found in the sample with the contents of 177.44 microg/g and 69.32 microg/g, respectively. The method is rapid, sensitive and accurate for the content determination of residual solvents in flunixin meglumine raw material. PMID- 22667102 TI - [Determination of target compounds in cefoperazone sodium and tazobactam sodium for injection by capillary electrophoresis]. AB - A capillary zone electrophoresis (CZE) method was developed for the simultaneous determination of cefoperazone sodium and tazobactam sodium in the injectable powder of cefoperazone sodium and tazobactam sodium with hydrochlorothiazide as the internal standard. The operation was carried out on a quartz capillary (75 cm x 75 microm i. d. , 63 cm effective length). The electrophoretic conditions were as follows: 40 mmol/L borax solution as the back ground electrolyte (BGE), 12. 0 kV applied voltage, 220 nm as the detection wavelength; the sample solution was injected by hydraulic pressure for 10 s at the height of 10 cm. The cefoperazone and tazobactam showed good linear relationship in the ranges of 0.25-3.96 g/L and 0.062-0.99 g/L with the correlation coefficients of 0.999 5 and 0.999 6, respectively. The relative standard deviations of relative peak areas were less than 3%. The preparation was stable in 208 min. The recovery results met the methodology requirements. The method is simple, rapid, reproducible, and suitable to control the quality of cefoperazone sodium and tazobactam sodium injectable powder. PMID- 22667103 TI - [Determination of glyoxalate and oxalate by capillary zone electrophoresis]. AB - A method for the simultaneous determination of glyoxalate and oxalate by capillary zone electrophoresis (CZE) was developed. The influences of type, concentration and pH of the running buffer, and the applied voltage on separation were investigated. Glyoxalate and oxalate were separated within 11 min under the conditions of 20 mmol/L borax-5.5 mmol/L potassium hydrogen phthalate (pH 9.0), applied voltage of 20 kV, and detected wavelength of 212 nm. The calibration curves of glyoxalate and oxalate showed good linearity in the ranges of 0.8 -20 g/L and 1.2-20 g/L, respectively. The correlation coefficients were 0.999 3 and 0.997 5, respectively. The limits of detection for glyoxalate and oxalate were 0.2 and 0.4 g/L (S/N = 3), respectively. The average recoveries at three spiked levels were 98.3%-102.5% with acceptable relative standard deviations of 0.35% 0.61%. This method is simple, low cost and high performance. The method was successfully used for the determination of glyoxalate and oxalate in real samples, and the assay results were satisfactory. PMID- 22667104 TI - [Plant-specific type III polyketide synthases superfamily: crystal structures and functions]. AB - Plant type III polyketide synthase (PKS) generates backbones of a variety of plant secondary metabolites with diverse functions, and has long been models to elucidate the relationship between the three-dimensional structure and function. More than 80 type IIII PKS crystal structures with different functions have been reported in Protein Data Bank, including the crystal structures of the well studied Chalcone Synthase of plant type III PKS, as well as the 6 other kinds of PKSs in the family, which are critical for understanding the structural basis for diverse starter molecule selectivity, polyketide chain length and the cyclization reaction. Structure-based analysis and site-directed mutagenesis are foundation for the investigation of enzyme engineering, genetic and metabolic engineering. This review summarized 7 plant-specific type III PKS in the aspects of their crystal structures and functions. PMID- 22667105 TI - [Electrospinning technology in tissue engineering scaffolds]. AB - Tissue engineering technology provides a new method to repair ill tissue and worn out organs. In tissue engineering, scaffolds play an important role in supporting cell growth, inducing tissue regeneration, controlling tissue structure and releasing active factor. In the last decade, electrospinning technology developed rapidly and opened vast application fields for scaffolds. In this review, we summarized the technological conditions of electrospinning for scaffolds, the study of electrospun fiber scaffolds applied in tissue cell cultivation, and some new directions of electrospinning technology for scaffolds. We also addressed development directions of electrospinning research for scaffolds. PMID- 22667106 TI - [Quantitative detection of anti-classical swine fever virus siRNA expression in cells by stem-loop RT-qPCR]. AB - RNA interference (RNAi) is a promising technology in development of specific antiviral therapy, but the quantitative detection of small interfering RNA (siRNA) expressed in vivo is the main challenge to assess its antiviral effect. In order to detect the siRNA molecules (siN1 and SiN2) particularly expressed in cells to inhibit the replication of classical swine fever virus (CSFV), serial specific stem-loop primers were designed and synthesized. Two of them (SLP-N1-6 and SLP-N2-8) were selected by screening in cross combination and successfully used in establishment of an optimal stem-loop RT-qPCR, which showed high specificity and sensitivity in detection of anti-CSFV siRNA expressed in PK-15 cells. The method was capable of detecting 10(2) to 10(8) copies of siRNA molecule with good parallel relationship (R(sq) = 0.999) and high amplification efficiency (Eff. = 98.2%). Therefore, the established stem-loop RT-qPCR can be used as an ideal tool in quantitative assessment of the anti-CSFV effects of RNAi in combination with detection of viral antigens using indirect immunofluorescent assay and TCID50, providing a novel technique for evaluating the antiviral effects of the siRNA expressed in anti-CSFV transgenic pigs to be established in future. PMID- 22667107 TI - [Evaluation on glucose-xylose co-fermentation by a recombinant Zymomonas mobilis strain]. AB - Co-fermentation of glucose and xylose is critical for cellulosic ethanol, as xylose is the second most abundant sugar in lignocellulosic hydrolysate. In this study, a xylose-utilizing recombinant Zymomonas mobilis TSH01 was constructed by gene cloning, and ethanol fermentation of the recombinant was evaluated under batch fermentation conditions with a fermentation time of 72 h. When the medium containing 8% glucose or xylose, was tested, all glucose and 98.9% xylose were consumed, with 87.8% and 78.3% ethanol yield, respectively. Furthermore, the medium containing glucose and xylose, each at a concentration of 8%, was tested, and 98.5% and 97.4% of glucose and xylose was fermented, with an ethanol yield of 94.9%. As for the hydrolysate of corn stover containing 3.2% glucose and 3.5% xylose, all glucose and 92.3% xylose were consumed, with an ethanol yield of 91.5%. In addition, monopotassium phosphate can facilitate the consumption of xylose and enhance ethanol yield. PMID- 22667108 TI - [Application of high efficiency promoters in microbial production of 4 hydroxybutyric acid]. AB - 4-Hydroxybutyric acid (4HB) is a psychotropic drug used for polymer synthesis such as poly (4-hydroxybutyric acid) (P4HB) and poly (3-hydroxybutyric acid-co-4 hydroxybutyric acid) (P3HB-co-4HB). 1,4-butanediol (BD) can be converted to 4 hydroxybutyric acid by alcohol dehydrogenase (DhaT) and aldehyde dehydrogenase (AldD). In this study, high efficiency promoters including T7 promoter and P(Re) promoter were cloned to increase expression of dhaT and aldD, and thus accelerate the conversion from BD to 4HB. A. hydrophila 4AK4 (pZQ01), the recombinant strain under the control of T7 promoter, produced 6.00 g/L 4HB from 10 g/L BD with the productivity increased by 43.20%. While A. hydrophila 4AK4 (pZQ04), the strain under the control of T7 promoter, produced 4.87 g/L 4HB from 10 g/L BD, and the productivity was increased by 16.23%. Thus, the gene expression was increased by T7 and P(Re) promoters, leading to an accelerated biosynthesis of 4HB. PMID- 22667109 TI - [Effects of dilution rate and carbon-to-nitrogen ratio on lipid accumulation by Rhodosporidium toruloides under chemostat conditions]. AB - The objective of this work is to investigate how dilution rate and carbon-to nitrogen (C/N) ratio affects lipid accumulation by Rhodosporidium toruloides AS 2.138 9 in continuous culture. Under steady-state conditions, the increase in dilution rate led to the decrease in lipid content and lipid yield. The highest lipid yield and lipid content at D = 0.02 h(-1) were 0.18 g lipid/g sugar and 57.1%, respectively, while the highest lipid productivity and biomass productivity were obtained at D = 0.14 h(-1). The increase in C/N ratio led to the increase in lipid content. The highest lipid content of 38% was obtained at C/N = 237. The highest lipid yield of 0.12 g lipid/g sugar was obtained at C/N = 92. However, the highest lipid productivity of 0.12 g/(L x h) was obtained at C/N = 32. No significant changes were observed in terms of fatty acid composition of the lipid produced under different C/N ratios, and these three fatty acids, palmitic acid, stearic acid and oleic acid, took over 85% in all samples. PMID- 22667110 TI - [Construction of a recombinant Escherichia coli BL21/ pET-28a-lpgad and the optimization of transformation conditions for the efficient production of gamma aminobutyric acid]. AB - In order to enhance gamma-aminobutyric acid production from L-glutamate efficiently, we amplified the key enzyme glutamate decarboxylase (GAD) encoding gene lpgad from the strain Lactobacillus plantarum GB 01-21 which was obtained by way of multi-mutagenesis and overexpressed it in E. coli BL21. Then we purified GAD by Ni-NTA affinity chromatography and characterized the enzyme to optimize the conditions of the whole-cell transformation. The results showed that the recombinant E. coli BL21 (pET-28a-lpgad) produced 8.53 U/mg GAD, which was increased by 3.24 fold compared with the GAD activity in L. plantarum. The optimum pH and temperature of the enzyme were pH 4.8 and 37 degrees C, respectively. At the same time, we found that Ca2+ and Mg2+ could increase the activity significantly. Based on this, we investigated gamma-aminobutyric acid transformation in 5 L fermentor under the optimum transformation conditions. Accordingly, the yield of gamma-aminobutyric acid was 204.5 g/L at 24 h when the 600 g L-glutamate was added and the mole conversion rate had reached 97.92%. The production of gamma-aminobutyric acid was improved by 42.5% compared with that under the unoptimized transformation conditions. This paved a way for the gamma aminobutyric acid construction of the industrial applications. PMID- 22667111 TI - [Preparation of a monoclonal antibody against polyhedrin of Ectropis obliqua nucleopolyhedrovirus]. AB - To develop a method based on immunoreactions for detection of Ectropis obliqua Nucleopolyhedrovirus (EoNPV), the polyhedra of the virus were purified and used to immunize the mouse BALB/c. The spleen cells from the immunized mice were then fused with the myeloma cell line Sp2/0. A hybridoma cell line which can stably secrete the monoclonal antibody against EoNPV was achieved by using indirect ELISA screening and cloning methods, and was named as 7D3. Meanwhile, the polyhedrin gene was cloned from EoNPV and expressed in E. coli. Western blotting analysis showed that the monoclonal antibody prepared from 7D3 could specifically react with the recombinant polyhedrin. An indirect ELISA method based on this monoclonal antibody for detecting EoNPV in infected tea looper was developed. PMID- 22667112 TI - [Construction and sequence analysis of a drought-induced full-length cDNA library from Ammopiptanthus mongolicus]. AB - Ammopiptanthus mongolicus shows very strong resistance to severe environments. To isolate drought-resistant genes and elucidate drought-resistant molecular mechanisms of the plant, we constructed a drought-induced full-length cDNA library using SMART (Switching mechanism at 5'-end of RNA transcript) technique. The phage titer of the unamplified library was 1.6 x 10(7) PFU/mL; the recombination percentage was 97.7%; and the sizes of most cloned cDNA fragments were around 1 kb. Three thousand positive clones were randomly selected and sequenced from their 5' ends, and a total of 1 450 Unigenes were identified. By Blast searches against the Nt, Nr and Swissprot databases, we found that 919 Unigenes (amount to 63.4%) showed significant similarity to the annotated genes, and the remaining 531 Unigenes (amount to 36.6%) represented novel genes without any annotation. Among the functional categories of the GO (Gene Ontology) classification, the terms related to physiological process, cellular process, binding, catalytic activity and cellular components were dominant. The next abundant terms were for organelle, protein complex, transporter activity and structural molecule activity. In addition, there were a significant proportion of the terms involved in stimulus response, gene expression regulation, regulation of physiological and biochemical processes and signal transduction. Many of the annotated Unigenes were found to be related to plant resistance to abiotic stresses, and expression analyses of 6 out of these genes by semi-quantitive RT PCR confirmed their involvements in the response of A. mongolicus to drought stress. These results laid a foundation for the expression profile analysis and the cloning and characterization of drought-resistant genes from the plant in the future. PMID- 22667113 TI - [11'-Deoxyverticillin A induces caspase-dependent cell apoptosis in PC3M cells]. AB - Recent years, the incidence and mortality of prostate cancer have increased dramatically in China. At earlier stages, most diagnosed prostate cancers are responsive to androgen depletion treatment, yet, nearly all patients will eventually progress to metastatic androgen-independent prostate cancer (AIPC), which still has no effective therapeutic method or drug to deal with. 11' Deoxyverticillin A (C42) belongs to the family of epipolythiodioxopiperazines (ETPs), an interesting class of fungal toxins that inhibit farnesyl transferase. Compounds holding such a property have been explored as putative anticancer agents. In this study, using PC3M cells, an AIPC cell line, we investigated the effect of the compound on apoptosis and explored the underlying mechanism. It revealed that C42 markedly enhanced the activity of caspase-3/7 and increased the accumulation of the cleaved PARP, all of which are the markers of apoptosis. It also revealed that C42 either decreased cell viability or inhibited the growth of PC3M cells. Moreover, we observed that the loss of cell viability and cell growth inhibition induced by C42 were both time- and dosage dependent. Taken together, we indicated that C42 can induce caspase-dependent apoptosis in AIPC cells, and the results presented here will broaden our knowledge about the molecular mechanisms by which C42 exerts its anticancer activity, and future work in this direction may provide valuable information in the development of these compounds into effective cancer therapeutic strategies against androgen-independent prostate cancer. PMID- 22667114 TI - [High efficiency genome walking method for flanking sequences of cotton mitochondrial double-copy atpA gene based on optimized inverse PCR and TAIL-PCR]. AB - Cloning of flanking sequences of double-copy gene is a challenge in molecular biology. We developed a method to solve this problem by combining an optimized inverse PCR (iPCR) with TAIL-PCR. First, Southern blotting analysis was used to determine a proper restriction enzyme that could obtain proper-length restriction fragments that contained the target gene. Then optimized iPCR was performed to amplify the restriction fragments that contained the separated copies of the gene. Based on the obtained sequences, TAIL-PCR was performed to amplify further flanking regions of the gene. With this method, we obtained all of the EcoR I restriction fragments (2.2-5.1 kb) and Hind III restriction fragments (8.5-11.7 kb) of mitochondrial atpA gene in cytoplasmic male sterile (CMS) line and maintainer line of Upland cotton. The results showed that this method was an efficient approach to clone flanking sequences of double-copy gene. PMID- 22667115 TI - [A new miRNA story about tumor metastasis]. PMID- 22667116 TI - [Engineering and screening of artificial riboswitch as a novel gene control element]. AB - Various artificial riboswitches have been constructed by utilization of designed aptamers or by modification of natural riboswitch systems, because they can regulate gene expression in a highly efficient, precise and fast way, and promise to supply simple cis-acting, modular, and non-immunogenic system for use in future gene therapy applications. In this review, we present an overview of currently available technologies to design and select engineered riboswitches, and discuss some possible technologies that would allow them highly responsive to non-natural ligands, and dynamic control of gene expression in mammalian cells. Though how to bring custom-designed riboswitches as a novel and versatile tool box to gene control system is still a great challenge, the combination of structure-activity relationship information, computer based molecular design, in vitro selection, and high-through screening will serve as powerful tools for further development of riboswitch based gene regulatory systems. PMID- 22667117 TI - [Regulation of plant height by gibberellins biosynthesis and signal transduction]. AB - Plant height is one of the most important agronomic traits that could affect both crop yield and quality. Among all the hormones, gibberellins are crucial to regulate plant height. Cloning and molecular mechanism research of the plant height genes associated gibberellins have extremely important value for the regulation of crop growth and agricultural production, and have been widely used in rice, wheat and other grain crops breeding. In order to promote utilization of gibberellins in fruit trees, flowers and other horticultural crops breeding, we reviewed the regulation of plant height by gibberellins biosynthesis and signal transduction at the molecular level in this paper. PMID- 22667118 TI - [Roles of phosphatases in pathogen infection: a review]. AB - Phosphatases play a key role not only in cell physiological functions of an organism, but also in host-pathogen interactions. Many studies demonstrated that some Gram-negative pathogenic bacteria could evade host immunity and promote pathogenicity by injecting phosphatases into host cells through type III secretion system. However, there were few reports about pathogenic fungi evading the immunity of hosts. Our researches indicated that the entomogenic fungus Metarhizium anisopliae could dephosphorylate the signal transduction substance of locust humoral immunity specifically in vitro by secreting extracellular protein tyrosine phosphatase, which implied that the fungus might interfere with the immune defense of locust. To provide reference for further studies of the functions of phosphatases, we reviewed the types of phosphatases and their roles in pathogen infection. PMID- 22667119 TI - [Enhanced porcine interferon-alpha production by Pichia pastoris by methanol/sorbitol co-feeding and energy metabolism shift]. AB - Porcine interferon-alpha (pIFN-alpha) fermentative production by recombinant Pichia pastoris was carried out in a 10-L bioreactor to study its metabolism changes and effects on fermentation under different inducing strategies, by analyzing the change patterns of the corresponding metabolism and energy regeneration. The results show that the specific activities of alcohol oxidase (AOX), formaldehyde dehydrogenase (FLD) and formate dehydrogenase (FDH) largely increased when reducing temperature from 30 degrees C to 20 degrees C under pure methanol induction, leading significant enhancements in methanol metabolism, formaldehyde dissimilatory energy metabolism and pIFN-alpha antiviral activity. The highest pIFN-alpha antiviral activity reached 1.4 x 10(6) IU/mL, which was about 10-folds of that obtained under 30 degrees C induction. Using methanol/sorbitol co-feeding strategy at 30 degrees C, the major energy metabolism energizing pIFN-alpha synthesis shifted from formaldehyde dissimilatory energy metabolism pathway to TCA cycle, formaldehyde dissimilatory pathway was weakened and accumulation of toxic intermediate metabolite formaldehyde was relieved, and methanol flux distribution towards to pIFN-alpha synthesis was enhanced. Under this condition, the highest pIFN-alpha antiviral activity reached 1.8 x 10(7) IU/mL which was about 100-folds of that obtained under pure methanol induction at 30 degrees C. More important, enhanced pIFN alpha production with methanol/sorbitol co-feeding strategy could be implemented under mild conditions, which greatly reduced the fermentation costs and improved the entire fermentation performance. PMID- 22667120 TI - [Controlling the morphology of filamentous fungi for optimization of fermentation process]. AB - Filamentous fungi have been extensively used in industrial fermentation processes. One of the most interesting topics of filamentous fungi is their bothersome morphology, which closely correlates with the productivity and broth rheology. Aiming at the optimization of the microbial process, works mainly focused on the relationships between morphology, productivity and environment in the last decades. Based on those works, we tried to interpret the mechanism of filamentous fungi growth from physiological aspects, and reviewed the mathematical models describing the hyphal growth, differentiation during the formation of target products. Above all, efficient and effective morphology controlling strategies were addressed from the engineering view. PMID- 22667121 TI - [Effect of mutating subsite -7 on product specificity of cyclodextrin glucanotransferase from alkalophilic Bacillus clarkii]. AB - To investigate the mechanism of high product specificity of gamma-clodextrin glucanotransferase (CGTase) from alkalophilic Bacillus clarkii 7364, we aligned protein sequence and structure model, found out that loss of 6 amino acids at subsite -7 probably affected its product specificity. Using overlapping PCR method, we inserted 6 amino acids into subsite -7 of CGTase. The mutant CGTase gene was ligated with pET-20b (+) and expressed in Escherichia coli BL21 (DE3). The extracellular recombinant enzyme was used to transform soluble starch into cyclodextrins (CDs). HPLC analysis results show that, compared to wild CGTase, the gamma-CDs produced by mutant enzyme decreased from 76.0% to 12.5%, whereas the ratio of alpha- and beta-CDs increased from 8.7% and 15.2% to 37.5% and 50%. The possible mechanism was that, compared to alpha-, beta-CGTase, wild gamma CGTase lacks 6 amino acids in its subsite -7. This conformation provided more space for glucose combination and was thus advantageous for forming gamma-CD. When the 6 amino acids were inserted into the subsite -7 of wild gamma-CGTase, the space to bind with glucose reduced and consequently resulted in less gamma-CD production. PMID- 22667122 TI - [Agrobacterium-mediated genetic transformation of secondary somatic embryos in alfalfa]. AB - We describe a genetic transformation method of secondary somatic embryogenesis in alfalfa through cotyledon-stage somatic embryos of alfalfa infected by Agrobacterium strain GV3101. The Agrobacterium strain GV3101 contained binary vector pCAMBIA2301 that had gus gene as reporter and npt II gene as selectable marker. The infected primary embryos were induced through series of medium under 75 mg/L kanamycin selection. We obtained the transgenic alfalfa plants. Then, GUS expression in different tissue of transgenic alfalfa was tested by GUS histochemical analysis. Further, the stable integration and transformation efficiency were tested by polymerase chain reaction and Southern blotting hybridization. The result showed that GUS expression was different in different organs of transgenic alfalfa; the copy number of integrated npt II gene was from 1 to 4; the transformation efficiency via primary somatic embryogenesis was 65.82%. PMID- 22667123 TI - [Differentiation of human amniotic mesenchymal stem cells into insulin-secreting cells induced by regenerating pancreatic extract]. AB - In this study, the natural biological inducer, rat regenerating pancreatic extract (RPE), was used to induce human amniotic mesenchymal stem cells (hAMSCs) into insulin-secreting cells. We excised 60% of rat pancreas in order to stimulate pancreatic regeneration. RPE was extracted and used to induce hAMSCs at a final concentration of 20 microg/mL. The experiment methods used were as follows: morphological-identification, dithizone staining, immumofluorescence analysis, reverse transcription-PCR (RT-PCR) and insulin secretion stimulated by high glucose. The results show that the cell morphology of passge3 hAMSCs changed significantly after the induction of RPE, resulting in cluster shape after induction for 15 days. Dithizone staining showed that there were scarlet cell masses in RPE-treated culture. Immumofluorescence analysis indicated that induced cells were insulin-positive expression. RT-PCR showed the positive expression of human islet-related genes Pdx1 and insulin in the induced cells. The result of insulin secretion stimulated by high glucose indicated that insulin increasingly secreted and then kept stable with prolongation of high glucose stimulation. In conclusion, hAMSCs had the potential to differentiate into insulin-secreting cells induced by RPE in vitro. PMID- 22667124 TI - [Reconstruction of erythromycin macrocyclic lactone synthesis pathway in Escherichia coli]. AB - We reconstructed the erythromycin macrocyclic lactone (6-deoxyerythronolide B, 6dEB) synthesis pathway in Escherichia coli. We first cloned all the genes needed to synthesize the 6dEB into multi-gene co-expressed vectors. Then using the recognition sequences of isoschizomers Xba I/Spe I of vectors, we assembled the related genes into a series multiple-genes recombinant plasmids pBJ144, pBJ130. The recombinant plasmids pBJ144, pBJ130 were cotransformed into BAP1 to get the recombinant BAP1(pBJ144/pBJ130). SDS-PAGE analysis showed that individual genes were expressed correctly. After inducing at low temperature, adding propionate as substrate, we validated the crude product by mass spectrometry and the 6dEB yield was about 10 mg/L. These results indicated that the synthetic pathway of 6dEB was successfully assembled and reconstructed in Escherichia coli, which will greatly facilitate the reconstruction of whole erythromycin synthesis pathway and finally help to establish a stable research platform for developing of new derivatives of erythromycin and combinatorial biosynthesis of polyketide-type antibiotics. PMID- 22667125 TI - [Expression, purification of proteasome subunit PSMB1 and application in screening of possible proteasome inhibitors]. AB - Proteasome is a multi-subunit protease complex in eukaryocytes, and plays an important role in ubiquitin-proteosome pathway. Recombinant proteasome can be used to screen proteasome inhibitors. In this study, recombinant plasmid of pET28a-PSMB1 was constructed by inserting human proteasome catalytic subunit (PSMB1) cDNA (726 bp) into the prokaryotic expression vector pET28a(+), and transforming the plasmid into E. coli BL21(DE3) cells for expression. After overnight induction (1 mmol/L IPTG, 20 degrees C), an expected protein band with molecular weight of 27 kDa was observed on SDS-PAGE gel. The recombinant protein was then purified through affinity chromatography, and the purity is more than 95%. The amino acid sequence of the recombinant protein was validated by NanoLC MS/MS. The data from in vitro BIAcore analysis showed that the recombinant PSMB1 could bind to celastrol. The binding affinity between PSMB1 and 10 micromol/L celastrol was more than 27RU. PMID- 22667126 TI - Design and biological activity of beta-hairpin-like antimicrobial peptide. AB - In the current study, we synthesized a 16-residue-long peptide VR with the aim of inspecting the feasibility to design beta-hairpin-like antimicrobial peptide. The peptide was designed by alternating arrangement of arginine and valine and linking two stranded antiparallel beta-sheet with a short loop segment (DPG) and a disulfide bridge. Antimicrobial and hemolytic activities were investigated. Melittin was chosen as a control peptide. We also tested bactericidal kinetics and salt sensitivity. Results show that VR had similar antibacterial activity compared with melittin. However, VR displayed much less hemolytic activity than melittin. These results suggest that VR had higher cell selectivity than melittin. The antibacterial activity of VR was not inhibited in the presence of 25 and 50 mmol/L NaCl. VR still possessed antibacterial activity in the presence of 100 mmol/L NaCl. Collectively, the de novo peptide VR displayed high antimicrobial activity, low hemolytic activity, and salt resistant, indicating that VR was a promising candidate for novel antimicrobial applications. PMID- 22667127 TI - [Micromorphological observation of bacterial biofilms on ciliated epithelia of chronic rhinosinusitis]. AB - OBJECTIVE: To observe the micromorphological characteristic of bacterial biofilm on mucosa of chronic rhinosinusitis (CRS). METHOD: Mucosa samples of middle turbinate were obtained from 4 patients of CRS during ESS. The size of each sample was about 4 mm x 4 mm. The samples were fixed in 4% paraformaldehyde for 24 hours, then fixed in 1% osmium tetroxide for 2 hours, graded dehydration with ethanol, dried with carbon dioxide and sputter coated with gold. The ultrastructure of these samples was observed by scanning electron microscope. RESULT: Bacterial biofilms were found on samples in all 4 patients. The biofilms were mainly formed on the surface of cilia. The bacterial flagella and cilia were intertwined. The biofilms could be found in a lot kinds of bacterial infections or mixed infections which were caused by multiple bacteria and fungi. CONCLUSION: Bacterial biofilm could be formed on ciliated epithelia. PMID- 22667128 TI - [The association between genetic polymorphisms of IL-6 and the susceptibility of chronic rhinosinusitis]. AB - OBJECTIVE: To investigate the relationship between the promoter polymorphism of IL6 (-174G > C, -572G > C and -597G > A) and chronic rhinosinusitis (CRS). METHOD: The case-control study consisted of 123 patients with CRS and 239 controls from a Chinese Han population from Shanghai. The genotypes of the subjects were determined by polymerase chain reaction-restriction fragment length polymorphism and gene sequencing. Besides, the concentrations of the totle immunoglobulin E (TIgE) and eosinophilic cationic protein (ECP) in the blood were also determined. RESULT: The -174G > C and -597G > A polymorphisms were not detected in this study population. Significant differences in genotype and allele frequencies of -572C/G were observed between CRS patients and control groups. In CRS patients, the CC, CG, GG genotype frequencies were 69.1%, 29.3%, 1.6%, C, G allele frequencies were 83.7%, 16.3%. In control group, the genotype frequencies were 55.2%, 42.3%, 2.5%, the allele frequencies were 76.4%, 23.6%, respectively. The -572CC genotype was associated with an increased risk of developing CRS (P < 0.05, OR = 1.932, 95% CI, 1.205-3.097). There was no significant differences in the concentrations of the TIgE and ECP among each genotype. CONCLUSION: IL-6 gene -572G > C polymorphism is associated with the susceptibility to CRS. CC genotype could be an independent risk factor. PMID- 22667129 TI - [Isolated sphenoid sinus disease: a clinical analysis of 159 cases]. AB - OBJECTIVE: Aimed to observe and analyse the diagnostic and therapeutic methods of the isolated sphenoid sinus disease, achieve earlier diagnosis and timelier intervention for this easily neglected disease and decrease the occurrence of misdiagnoses. METHOD: A retrospective study was conducted in 159 patients with isolated sphenoid sinus disease. RESULT: Headache was the most common presenting symptom (79.87%,127/159). Among the 159 cases, 60 (37.74%) had mucocele, 44 (27.67%) isolated sphenoiditis, 31 (19.50%) fungal sinusitis, 5 (3.14%) polyp, 3 (1.89%) fibrous dysplasia, 2 (1.26%) inverted papilloma, 3 (1.89%) chordoma, 3 (1.89%) squamous carcinoma, 3 (1.89%) malignant lymphoma, 2 (1.26%) neuroendocrine carcinoma, 2 (1.26%) olfactory neuroblastoma, and 1 (0.63%) malignant fibrohistiocytoma. A follow-up of 10 months to 4 years post-surgery showed good prognosis in most of the patients who underwent surgical therapy. CONCLUSION: The sphenoid sinus disease is often vague and nonspecific in its clinical presentation. The most common clinical symptom is headache, followed by vision changes. Endoscopic sphenoidotomy is the primary therapy for isolated sphenoid sinus disease. PMID- 22667130 TI - [To study of the nasal mucosa remodeling of allergic rhinitis patients]. AB - OBJECTIVE: To explore whether there was tissue remodeling in the nasal mucosa of allergic rhinitis (AR) patients and detect the protein expressions of transforming growth factor beta1 (TGF-beta1), matrix metalloproteinases 9 (MMP-9) and tissue inhibitors of matrix metalloproteinases 1 (TIMP-1) in the nasal mucosa of these patients. METHOD: Pathologic staining was used to explore the mucosa of the middle turbinate tissues from 16 patients with mild AR, from 12 patients with severe AR, and from 15 non-AR, respect. The infiltrating of eosinophils and damage of epithelium were examined by the hematoxylin-eosin staining; goblet cells were counted by the alcian blue-periodic acid-schiff staining; the percentage area of extracellular matrix was determined by the MT; the protein expressions were measured by ELISA of TGF-beta1, MMP-9 and TIMP-1 in the middle turbinate tissues. RESULT: Compared with the control group, significant eosinophil infiltration and goblet cells were observed in both AR groups (P < 0.05). Evident epithelial damage and extracellular matrix deposition were observed in severe-AR group (P < 0.05). The expressions of TGF-beta1, MMP-9 and TIMP-1 in AR tissues were significant increased (P < 0.05). CONCLUSION: The nasal mucosa remodeling was observed in AR groups. The characteristics were as follows: eosinophils infiltration, epithelial damage, goblet cells hyperplasia and extracellular matrix deposition. TGF-beta1, MMP-9, TIMP-1 may play a role in the tissue remodeling processes. PMID- 22667131 TI - [The expression of Treg/Th17 cells related transcription factors and cytokines in PBMCs and plasma in patients with allergic rhinitis]. AB - OBJECTIVE: To investigate the changes of Treg/Th17 cells related transcription factors (FOXP3, RORC) and cytokines (TGF-beta, IL-17) in the peripheral blood in patients with allergic rhinitis. METHOD: Use visual analogue scale (VAS) to assess the allergic rhinitis severity of patients. Eighteen patients with allergic rhinitis and 12 healthy control subjects were consecutively enrolled. Peripheral blood samples were obtained from all patients and healthy control subjects (after prick test). The mRNA expressions of key transcription factors (RORC, FOXP3) in PBMCs were measured by RT-PCR, and the concentrations of TGF beta, IL-17 in plasma were measured by ELISA. RESULT: Patients with moderate/severe persistent rhinitis have a VAS of 8.5 +/- 0.8, and total patients have a VAS of 6.2 +/- 1.6. Compared with healthy control subjects, the mRNA expressions of FOXP3 and the concentrations of TGF-beta in plasma were significantly lower in patients with allergic rhinitis (P < 0.01) while the mRNA expressions of RORC and the concentrations of IL-17 in plasma were significantly higher in allergic rhinitis group (P < 0.01). CONCLUSION: The imbalance of Treg/Th17 cells existed in allergic rhinitis patients, which may contribute to the proceeding of allergic rhinitis. PMID- 22667132 TI - [Skin prick testing versus immumofluorescence testing for mites allergens]. AB - OBJECTIVE: To discuss the characteristics of skin prick test (SPT) and immumofluorescence method (IFM) in detecting the atopy of dermatophagoides pteronyssinus (Dp) and dermatophagoides farinae (Df)and explore the relationship of them. METHOD: Four hundred and ninety-one patients with two or more symptoms of nasal obstruction,itching, sneezing and rhinorrhea received SPT and serum specific IgE detection using IFM. RESULT: SPT was more sensitive than IFM in detecting the atopy of Dp and Df (P < 0.05). If using the IFM as the gold standard, the sensitivity of SPT was all above 95% with the specificity a little bit lower than 80%. These two methods had a positive correlation in detecting the atopy of Dp and Df (r = 0.779, 0.776; P < 0.01). The sIgE concentrations of these two mites were highly correlated with each other (r = 0.954, P < 0.01), the SPT was highly correlated with each other (r = 0. 946, P < 0.01). CONCLUSION: SPT was more sensitive than IFM in detecting the atopy of Dp and Df. In most cases, SPT can replace IFM to detect patients' allergia on mites. Besides, it is good enough to detect either of the serum specific IgE concentrations of Dp and Df. PMID- 22667133 TI - [Analysis of allergic sieving detection results and clinical significance in children with allergic disease]. AB - OBJECTIVE: To explore the clinical use of sieving detection among the childhood with allergic disease. METHOD: The sieving detection about allergen inhalant allergens, Fx5 in the CAP anaphylactogen detection system, and serum specific IgE were detected in three hundred and thirty-one cases of children (aged from 1 year to 14 years old) with allergic disease. Patients were divided into group 1, group 2 and group 3 according to the age from 0 to 3, 3 to 6, and 6 to 14 years old. All datas were statistical analysed among different age groups. RESULT: Among the 331 patients, the positive rate of allergic sieving detection was 67.98%, the elevation rate of IgE was 53.78%. Inhalant allergen positive rate was 60.42%, while the food allergen positive rate was 28.10%. Inhalant allergen positive rate of the group 3 (aged from 6 to 14 years old) was significant higher than the other two age groups (68.45%). And the food allergen positive rate of the age group 1 (aged from 0 to 3 years old) was significant higher than the other two age groups (62.50%). Positive rate for simply inhalant allergen was 39.88%, while positive rate for simply food allergen was 7.55% and mixed allergen was 20.54%. CONCLUSION: Inhalant allergen was the main allergen of the children with allergic disease aged over 3 years old, while food allergen was the main allergen of the children with allergic disease aged below 3 years old. It was safe, sensible and effective to use Uni CAP anaphylactogen detection system for rapid assay of specific allergens. PMID- 22667134 TI - [Prolonged allergen challenge in a guinea pig model of allergic rhinitis leads to nasal mucosa remodeling]. AB - OBJECTIVE: The aim of this study was to use a guinea pig model of prolonged allergic-induced rhinitis to characterize the feature of nasal mucosa remodeling. METHOD: Forty-eight male Hartley guinea pigs were randomly divided into six groups: allergen challenged groups (Group OVA(2w) , Group OVA(6w) and Group OVA(12w)) and control groups respectively (Group Sal(2w), Group Sal(6w) and Group Sal(12w)). Each group had 8 guinea pigs. To develop a guinea pig model of nasal mucosa remodeling, ovalbumin-sensitized guinea pigs were repeatedly challenged with allergen twice a week from two weeks to 12 weeks. Matched control groups were challenged with physiological saline. Nasal lavage was performed 24 hours after the last intranasal challenge. Then nasal mucosa were obtained. HE, AB-PAS, MT, and immunohistochemical staining against transforming growth factor-beta1 (TGF-beta1) were performed. Eosinophil cationic protein (ECP) and OVA-special IgE (OVA-sIgE) were detected by ELISA in nasal lavage fluid. RESULT: (1) The levels of OVA-sIgE in nasal lavage fluid in Group OVA(6w) and Group OVA(12w) were significantly different from Group OVA(2w), while the levels of ECP had no significant difference among the experiment groups. The levels of OVA-sIgE and ECP in experiment groups were significantly different from control groups respectively (P < 0.01). (2) Grade 0 and Grade 1 of epithelial damage were significantly different in Group OVA(6w) and Group OVA(12w) when compared with from Group OVA(2w) (P < 0.01). At the same time, Grade 0 and Grade 1 of epithelial damage were statistically different in the experiment groups when compared with the respectively control groups (P < 0.05). (3) Goblet gland hyperplasia and collagen deposit within the extracellular matrix (ECM) were easily found in Group OVA(6w) and Group OVA(12w) compared with Group OVA(2w) (P < 0.01). The number of goblet gland and the ratio of collagen deposit were statistically more in Group OVA(6w) and Group OVA(12w) than in Group Sal(6w) and Group Sal(12w) (P < 0.05). That feature of the ratio of collagen deposit did not show in Group OVA(2w) versus Group Sal(2w). (4) Increased TGF-beta1 expressions were observed in Group OVA(6w) and Group OVA(12w) compared with Group OVA(2w) (P < 0.01). Those increasing expressions were also observed in experiment groups rather than in the respectively control groups (P < 0.01). CONCLUSION: Epithelial damage, goblet cells hyperplasia and collagen deposition in ECM were observed as the features of remodeling in this guinea pig model of allergic rhinitis under prolonged allergen challenge. Epithelial damage, excessive expression of related cytokines and enhancement activity of enzymes were observed in early time after challenge of allergen. The features of goblet cells hyperplasia and collagen deposition in ECM were observed at a later stage. PMID- 22667135 TI - [Overview on quantitative analysis of multi-components by single-marker]. AB - Based on the previous literatures, the overview on the history and recent advance of the quantitative analysis of multi-components by single-marker (QAMS) was summarized. The key questions of QAMS were also highlighted. It could be considered as a feasible method for the quality control of Traditional Chinese Medicines. PMID- 22667136 TI - [Research progress of the anti-proliferation effect of emodin on VSMCs]. AB - Emodin has such pharmacological effects as ant-inflammatory, anti-tumor, immunoregulation. Meanwhile, emodin could be used for inhibiting the proliferation of vascular smooth muscle cells (VSMC). Many foreign studies demonstrated that emodin had an effect on inhibiting proliferation of VSMCs and cell migration and promoting cell apoptosis, and probed into molecular mechanisms in all aspects. Besides, clinical translational researches and application explorations were also carried out. This article summarizes the research progress of the anti-proliferation effect of emodin on VSMCs. PMID- 22667137 TI - [Neuroprotective effect of baicalein in patients with Parkinson's disease]. AB - Baicalein, a flavonoid compound extracted from dried roots of traditional Chinese medicine Scutellaria baicalensis, has been widely applied as an antioxidant and anti-inflammatory agent. With continuous studies on its mechanisms, recent findings suggest that baicalein has some effect on neuroprotection and improvement of clinical symptoms in neurodegenerative diseases such as Parkinson's disease. Recent studies showed that its neuroprotective efficacy is closely related to such functions as antiinflammatory, antioxidative stress, protecting chondriosome, inhibiting glutamate neurotoxicity, promoting nerve growth and inhibiting alpha-synuclein protein-aggregate activities. The aim of this article is to summarize the neuroprotective effects of baicalein in Parkinson's disease. PMID- 22667138 TI - [Research on relationship between commercial specifications of Scutellariae Radix and chemical composition and drug quality]. AB - OBJECTIVE: To compare the chemical differences in 4 commercial specifications of Scutellaria Radix, research the affection of decayed central xylem part on the crude drug's chemical composition and provide scientific data for production, processing, sale and clinical applications of Scutellariae Radix. METHOD: Macroscopical identification method was used for observation of different specifications of Scutellariae Radix, including Qinwang, Tiaoqin both in 1st class and 2nd class and inferior samples. HPLC fingerprint method was used to analyze chemically the decayed central xylem part and non-decayed part as well as complete sample, and the results were described by the relative peak area. RESULT: The morphological characteristics of 4 specifications are greatly different from one another mainly in root diameters, root lengths and the proportions of decayed central xylem part in the root, and so the authors classified Qinwang and Tiaoqin in 1st class as Kuqin for all samples of them which have decayed central xylem; and classified Tiaoqin in 2nd class and the inferior samples as Ziqin, for having little decayed central xylem. The 4 specifications collected from the same producing area have similar HPLC fingerprint profile to one another, while they are different in relative peak area. The peak area ratios of aglycone to their glucuronide (baicalein/baicalin, wogonin/wogonoside, oroxylin A/oroxylin A-7-O-glucuronide) from Kuqin were significantly higher than those of Ziqin. The total area of the peaks in HPLC fingerprint chromatographs of decayed central xylem part were quite lower than that of non-decayed part, whereas peak areas of the characteristic peaks and the 3 peak area ratios of decayed central xylem were significantly higher than those of non-decayed part which could be used as characteristic parameters to distinguish Kuqin and Ziqin. CONCLUSION: Four commercial specifications of Scutellariae Radix can be classified as Kuqin and Ziqin respectively according to morphological characteristics and the proportions of decayed central xylem part in the root. The chemical characteristics of Kuqin and Ziqin are different from each other, so it's worth clarifying the similarities and differences of Kuqin and Ziqin in future. The result in this research can be used as references for identification and quality control of Scutellariae Radix specifications, and investigation on effective components of Kuqin and Ziqin. PMID- 22667139 TI - [Study on plant regeneration from somatic embryos of vulnerable medicinal plant Glehnia littoralis]. AB - OBJECTIVE: To study the cause of the seeds dormancy of Glehnia littoralis in vitro and to establish plant regeneration methods via somatic embryos. METHOD: The effects of endosperm and exogenous hormone on the seed dormancy breaking of G. littoralis and the effect of hormone concentration on embryonic callus induction and plant regeneration via somatic embryos were observed, RESULTS: The germination rate of the seeds with 1/3 endosperm was the highest which achieved 31%. TDZ, 6-BA and GA3 treatment could not break seed dormancy but easily lead to abnormal seedlings. Embryogenic callus induction rates was up to 57% on MS supplemented with 1.0 mg x L(-1) 2,4-D. After 20 days culture, embryogenic calli were transferred to MS medium and cotyledonary embryos were formed in 40 days. The regenerated plants were obtained in 20 days. CONCLUSION: An effective system of plant regeneration of G. littoralis was established in this study. PMID- 22667140 TI - [Microstructure and histochemical localization of flavonoids in leaves and stem in Sarcandra glabra]. AB - Microscopic and histochemical methods were used to investigate flavonoids localization in the leaf and the stem of the Sarcandra glabra. The results indicated that flavonoids distributed mainly in epidermis, collenchyma, vascular bundles, secretory cells and palisade tissue of leaf. In the stem, they distributed mainly in epidermis, collenchyma, phloem and secretory cells. Histochemical localization of flavonoids using 5% solution of NaOH is convenient, rapid and reliable. The content of flavonoids in the leaf was higher those than in the stem. For sustainable utilization of the resources we suggested that only the leaves could be harvested. PMID- 22667141 TI - [Effects of light intensity on growth and photosynthetic characteristics of Tulipa edulis]. AB - OBJECTIVE: Present study was conducted to explore the growth and photosynthetic characteristics of Tulipa edulis under different light conditions (23%, 45%, 63%, 78%, 100% of full sunlight) and to determine the optimum light intensity for growth of T. edulis. METHOD: The leaf area and biomass indicators as well as reproductive characteristics were measured. The photosynthetic basic parameters and light response curve were determined by a LI-6400XT portable photosynthesis system, and the light response curve characteristic parameters was determined. Additionally, chlorophyll fluorescence parameters were determined by assorted fluorescence leaf chamber of LI-6400XT. RESULT: The lowest biomass yield was observed in the 23% and 100% of full sunlight treatments while the highest value was found under the 78% of full sunlight conditions. With the reduction of light availability, the success rate of sexual reproduction, light saturation point (LSP) and light compensation point (LCP) reduced, while apparent quantum yield (AQY) increased. 23% and 45% of full sunlight treatments led to lower photosynthesis rate (Pn) and higher apparent quantum yield (AQY) in comparison with other treatents. The highest photosynthesis rate was observed in the 78% and 100% of full sunlight treatments. In addition, 78% of full sunlight treatments led to highest Fv/Fm, Fv'/Fm', PhiPS II, ETR, and qP. CONCLUSION: T. edulis was able to adapt in a wide range of light intensity, and 78% of full sunlinght was the most suitable light condition for growth of T. edulis. PMID- 22667142 TI - [Primary study on quality standard of carbonizing drug characteristic of ginger carbon]. AB - OBJECTIVE: To establish the quality standard for carbonizing drug characteristic of ginger carbon. METHOD: Gingers and different carbonized gingers were compared by the absorption of pigment, tannin content, pH, mouth's coagulation time and bleeding time. RESULT: The study resulted in the recommended carbonizing standard that the absorption capacity shall not be less than 7.50 mg x g(-1) for methylene blue, the tannin content shall not be less than 2.103 mg x g(-1), the pH shall be (5.50 +/- 0.10), and coagulation time and bleeding time shall be the shorter the better. CONCLUSION: The established assessment standard for carbonizing drug characteristic of ginger carbon is reasonable, easily operated and feasible. PMID- 22667143 TI - [Study on extraction and immune regulation of polysaccharides from Marsdenia tenacissima]. AB - OBJECTIVE: To optimize the extraction technology and determine the immune activity of polysaccharides from Marsdenia tenacissima. METHOD: The optimum extraction technology of polysaccharide from M. tenacissima was detected by orthogonal experiments with the extraction rate of polysacchride and the total sugar content as indicators. The immunocompromised mice model was established by intraperitoneal injection cyclophosphamide to detected the content of IL-2, IL-6 in serum, CD4+, CD8+ in the peripheral blood by ELISA and flow cytometry, respectively. RESULT: By the extraction rate of polysaccharide, the sequence of seriousness of all affecting factors from high to low was extracting times, temperature, heating time and water ratio. By the total sugar content, the sequence was temperature, extracting times, water ratio and heating time. Compared with the model group, the pleen index, IL-2, IL-6, CD4/CD8+ were increased significantly (P < 0.05) in the 0.14 g x kg(-1) group and 0. 28 g x kg( 1) group. CONCLUSION: T he optimum extraction condition was as follows: extraction three times/1.5 hours at 100 degrees C with 1:8 ratio of M. tenacissima to water. The polysaccharide of M. tenacissima can enhance the cellular immune and humoral immune. PMID- 22667144 TI - [Study on compatibility extraction technology of Rhei Radix et Rhizoma, Scutellariae Radix and Phellodendri Chinensis Cortex]. AB - OBJECTIVE: To determine the optimum compatibility extraction technology of Rhei Radix et Rhizoma, Scutellariae Radix and Phellodendri Chinensis Cortex. METHOD: The drugs were combined respectively firstly, then use HPLC to determinate extraction rates of evaluating indicators including emodin, chrysophano, baicalin and berberine hydrochloride. Orthogonal experiment was used to detect the effect on concentration and volume of ethanol, times of extraction. RESULT: The extraction rates of evaluating indicators were relatively high in combined extraction of Rhei Radix et Rhizoma with Scutellariae Radix and single extraction of Phellodendri Chinensis Cortex. The optimized combined extraction were 12 times more than the volume of 60% ethanol solution, by boiling for 3 times, each for 1.0 hour, and that of single extraction were 10 times more than the volume of 60% ethanol solution, by boiling for 3 times, each for 1.0 hour. CONCLUSION: The optimized compatibility extraction technology is reasonable, stable and practical. PMID- 22667145 TI - [Preparation of kappa-carrageenan-chitosan polyelectrolyte gel beads]. AB - OBJECTIVE: To prepare kappa-carrageenan-chitosan polyelectrolyte gel pellets and detect the effects of formulation and preparation factors on in vitro drug release from the pellets. METHOD: The K-carrageenan-chitosan polyelectrolyte gel pellets with baicalin as model drug were prepared by ionotropic gelation technique. The ratio of kappa-carrageenan/chitosan in pellets was determined with the composite of K-carrageenan and chitosan. The effects of the concentration of K-carrageenan, the ratio of drug/kappa-carrageenan, the concentration of gelling solution, gelling time and drying method on the release of pellets were determined by in vitro drug release. RESULT: The mass ratio of K carrageenan/chitosan in pellets was 6: 4. Release of the pellets in 0.1 mol x L( 1) HCl was about 10% for 2 hours and fast in PBS, indicating a typical sustained release property. The pellets released less with the increase in the concentration of K-carrageenan, the ratio of drug/kappa-carrageenan and the concentration of KCl. They also released less with the increase in gelling time, but showed little effect until 1 hour. The release of the pellets prepared by the freeze-drying method was much faster than those by vacuum drying and atmospheric drying methods which had little influence on drug release. CONCLUSION: The K carrageenan-chitosan polyelectrolyte gel pellets had sustained release property. Their drug release rate could be regulated with different formulation and preparation factors. PMID- 22667146 TI - [Chemical constituents from n-butanol extract of aerial part of Polygala sibirica]. AB - Nine compounds were isolated from the n-butanol extract of the aerial parts of Polygala sibirica by various column chromatographic methods. Their structures were identified by MS and NMR spectroscopic data as sibiricaxanthone F (1), amentoflavone (2), linarin (3), zigu-glucoside I (4), 3, 6'-disinapoyl sucrose (5), tenuifoliside A (6), 2, 4, 4-trimethyl-3-formyl-6-hy-droxy-2, 5 cyclohexadien-1-one (7), lanierone (8), and aralia cerebroside (9) , respectively. Compounds 2, 3, 4, 7, 8 were isolated from the genus Ploygala for the first time, and compound 9 was firstly isolated from the title plant. PMID- 22667147 TI - [Study on chemical constituents of Lycopodium alkaloids]. AB - OBJECTIVE: To study the alkaloid chemical constituents of Lycopodium japonicum. METHOD: Compounds were isolated and purified by such methods as silica gel column chromatography, RP-C18 reversed phase column chromatography, Sephadex LH-20 column chromatography and Waters semi-preparative liquid chromatogram, and their structures were identified based on physicochemical property and spectrum data. RESULT: Nine known alkaloid chemical constituents were isolated and identified, they were lycodoline (1), lucidioline (2), alpha-obscurine (3), lycopodine (4), lycoposerramine-L (5), lycoposerramine-M (6), 11alpha-O-acetyl-lycopodine (7), des-N-methyl-a-obscurine (8), clavolonine (9). CONCLUSION: Compounds 4-9 were obtained from L. japonicum for the first time. PMID- 22667148 TI - [Study on flavonoid chemical constituents contained in Memorialis hirta]. AB - OBJECTIVE: To study the chemical constituents of Memorialis hirta. METHOD: Compounds were isolated and purified by multiple methods, and their structures were identified based on physicochemical property and spectrum data. RESULT: 12 compounds were isolated from ethyl acetate from 95% ethanol extracts of M. hirta, they were isorhamnetin (1), kaempferol (2), quercetin (3), isorhamnetin-3-O-alpha L-rhamnopyranoside (4), kaempferol-3-O-alpha-L-rhamnopyranoside (5), isorhamnetin 3-O-beta-D-glucopyranoside (6), kaempferol-3-O-beta-D-glucopyranoside (7), quercetin-3-O-alpha-L-rhamnopyranoside (8), quercetin-3-O-beta-D-glucopyranoside (9), isorhamnetin-3-O-rutinoside (10), kaempferol-3-O-rutinoside (11) and quercetin-3-O-rutinoside (12), respectively. CONCLUSION: All compounds were obtained from the genus Memorialis for the first time. PMID- 22667149 TI - Chemical constituents of Rhododendron lepidotum. AB - An unusual natural product named 2,4,6-trihydroxacetophenone-3, 5-di-C-beta-D glucoside (18) were isolated from aerial parts of Rhododendron lepidotum grows in Tibet, along with other 17 known compounds: hopenol-B (1), lupeol (2), ursolic acid (3), avicularin (4), quercetin (5), myricetin (6), hyperoside (7), myricetin 3'-O-beta-D-xyloside (8), (+)-taxifolin-3-O-alpha-L-arabinopyranoside (9), (+) taxifolin-3-O-beta-D-glucopyranoside (10), lyoniside (11), confluentin (12), 2-(4 hydroxyphenyl)-ethyltriacontanoate (13), 2, 6-dimethoxy-4-hydroxyphenyl-1-O-beta D-glucopyranoside (14), (-)-2-hydroxy-5-(2-hydroxyethyl) phenyl-O-beta-D glucopyranoside (15), (-)-isola-riciresinol (16) and isofraxoside (17). All the compounds were firstly isolated from this plant as well as compounds 1, 13-18 were reported occurrence in R. spp. for the first time. The structures were identified based on analyses of spectroscopic data and physico-chemical evidences. PMID- 22667150 TI - [Effect of oral administration of glycyrrhetinic acid on six metal elements in rat serum]. AB - OBJECTIVE: To determine glycyrrhetinic acid concentration in rat plasma and concentration of calcium (Ca), copper (Cu), iron (Fe), potassium (K), magnesium (Mg) and sodium (Na) in rat serum after oral administration by LC-MS/MS and the flame atomic absorption method, and analyze the effect of glycyrrhetinic acid on the six elements in serum. RESULT: A similar variation trend between the concentration of glycyrrhetinic acid in plasma and that of Na, Cu elements in serum after oral administration of glycyrrhetinic acid was observed. Glycyrrhetinic acid in plasma at 2 h after administration reached the peak. Meanwhile, the concentration of Na and Cu at 4 h after the administration of glycyrrhetinic acid exhibited a significant increase (P < 0.05). Moreover, an increasing glycyrrhetinic acid dosage could result in the accumulation of Cu and Na in rat serum. Compared with the control group, the concentration of Cu and Na in the the glycyrrhetinic acid administration group with doses of 200 and 400 mg x kg(-1) revealed a significant increase (P < 0.05). However, glycyrrhetinic acid did not exhibit the great impact on the concentration of other elements in serum. CONCLUSION: This study focuses on the effect of oral administration of glycyrrhetinic acid on six metal elements in rat serum and provides an experimental basis for the adverse effect of glycyrrhetinic acid in clinical applications. PMID- 22667151 TI - [Study on HPCE fingerprints of Poecilobdella manillensis from Guangxi province]. AB - OBJECTIVE: To establish fingerprints for Poecilobdella manillensis from Guangxi province using the high performance capillary electrophoresis (HPCE) method. METHOD: Electrophoresis was performed on a fused silica capillary column (75 microm x 56 cm), with 25 mmol x L(-1) Na2HPO4-120 mmol x L(-1) Tris-16 mmol x L( 1) SDS (adjusted to pH 12.0 with 1 mol x L(-1) NaOH ) as the running buffer. The applied voltage was 17 kV, the temperature was 25 degrees C and the detection wavelength was 254 nm. The sample's hydrodynamic injection was 3.4 kPa x 6s and the duration was 27 min. RESULT: HPCE fingerprint was established with 13 common peaks. The similarity between fingerprints of P. manillensis in 10 batches and control fingerprints was more than 0.98. CONCLUSION: The method is so precise, reproducible and stable that it could be used as a new means for the quality control of P. manillensis. PMID- 22667152 TI - [Influence of Aconiti Lateralis Radix Praeparata on asthenia cold syndrome rats with whole genome gene expression of liver by gene chip technique]. AB - OBJECTIVE: To study the influence of Aconiti Lateralis Radix Praeparata on asthenia cold syndrome rats with whole genome gene expression of liver by gene chip technique. METHOD: The asthenia cold syndrome rat models were established by administering traditional Chinese medicine raw Gypsum Fibrosum, Gentianae Radix, Phellodendri Chinensis Cortex and Anemarrhenae Rhizoma. After treated with Aconiti Lateralis Radix Praeparata, the rats' liver gene expressions were detected using gene chip. Differential expression genes were screened for gene function annotation, and some genes were selected to check the accuracy of the results by RT-PCR. RESULT: Compared with the asthenia cold model group, the asthenia cold treatment group showed 212 differential expression genes, mainly involving function of immune response and oxidoreductase activity. CONCLUSION: Aconiti Lateralis Radix Praeparata is proved to have an effect on up-regulating immune response-related genes and oxidizing oxidoreductase activity-related genes of asthenia cold syndrome rats and may be a molecular mechanism for classical warm-nature medicine Aconiti Lateralis Radix Praeparata in warming meridians and dissipating cold. PMID- 22667153 TI - [Effect of gypenosides on DMN-induced liver fibrosis in rats]. AB - OBJECTIVE: To study the effect of gypenosides on DMN-induced liver fibrosis in rats. METHOD: A rat liver fibrosis model was established by injecting DMN intraperitoneally. Four weeks later, model rats were randomly devided into three groups: the model group, the gypenosides treated group (200 mg x kg(-1)) and the colchicine treated group (0.1 mg x kg(-1)), with 10 specimens for each group. After a 2-week treatment, following parameters were observed: (1) last body weight, weight ratio between liver and spleen; (2) content of liver hydroxyproline (Hyp); (3) activity of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (gamma-GT), content of albumin (Alb) and total bilirubin( TBiL) in serum; (4) liver pathology (Sirius red staining and HE staining); (5) activity of liver superoxide dismutase (SOD), glutathione reduced (GSH), glutathione peroxidase (GSH-Px) and content of liver maleic dialdehyde (MDA). RESULT: There were classic liver cirrhosis pathological changes in model groups. Compared with the normal group, liver Hyp content, activity of serum ATL, AST, gamma-GT and content of serum TBiL, MDA of model groups significantly increased; content of serum Alb and liver GSH, activity of liver SOD and GSH-Px decreased significantly in model groups. In comparison with the model group, liver cirrhosis remarkable improved in the gypenosides group, content of liver Hyp reduced significantly (P < 0.01), which was equal to the colchicine group. Compared with the model group, liver function parameters improved markedly in the gypenosides group; liver SOD and GSH-Px activities significantly increased; MDA content reduced significantly (P < 0.05). CONCLUSION: Gypenosides shows an effect in treating DMN-induced liver fibrosis in rats. PMID- 22667154 TI - [Study on functional recovery of hypoxic-ischemic brain injury by Rg1-induced NSCs]. AB - OBJECTIVE: To observe the effect of Rg1-induced NSCs in treatment of neonatal rat model with hypoxiaischemia. METHOD: The neonatal rat model of HIE was established and assessed by using TTC staining and behavioral observation, then Rg1-induced NSCs was transplanted into the neonatal rat of HIE by lateral ventricle injection. Water maze test and somatosensory evoked potential were detected to observe brain function and the immunohistochemistry was done to assess growth and differentiation about transplanted NSCs a month after transplanted. RESULT: The transplantation of Rg1-induced NSCs could significantly shorten incubation period, swimming distance, exploration time of target quadrants of water maze test and incubation period and amplitude of somatosensory evoked potentials. Additionally, the concentrated expression appeared in the hippocampus and grew around the ischemic injury area in transplantation group. CONCLUSION: Transplantation of Rg1-induced NSCs play a better role in the treatment of neonatal HIE rats. PMID- 22667155 TI - [Study on mechanism of ginsenoside Rg1-induced human neural stem cells differentiation by genechip]. AB - OBJECTIVE: The molecular targets of ginsenoside Rg1-induced neural stem cells (NSCs) differentiation were screened by genechip. METHOD: 7th day following ginsenoside Rg1 induced human neural stem cells to neurons the gene expression was observed by genechip. The purpose gene and signal transduction pathways were selected by the data calculations, and then confirmed by western blot and immunohistochemical method. RESULT: 7th day following Rg1-induced NSCs differentiation, there were about 675 different genes, 255 genes of which were up regulated and 420 genes down-regulated obviously. Meanwhile the ERK1/2 (extracellular signal-regulated protein kinase) in MAPK (mitogen-activated protein kinase) pathway was related with the NSCs differentiation. The Western blot and immunohistochemistry detection confirmed that ERK 1/2 protein and its phosphorylation were significantly increased, which can be blocked by PD98059 (ERK1/2 inhibitor). In addition, differentiation rate of NSCs was also decreased obviously in ginsenoside Rg1-induced differentiated NSCs when ERK blocker PD98059 was used. CONCLUSION: ERK1/2 is an important molecular target in ginsenoside Rg1 induced NSC differentiation. The selected differentially expressed genes by genechip may provide new clues to study of ginsenoside Rg1-induced NSCs differentiation. PMID- 22667156 TI - [Experimental study on inhibitory effect of GFW on transplantable tumor cell metastasis in S180 tumor-bearing mices]. AB - OBJECTIVE: To detect the effect of GFW on tumor cell metastasis in S180 tumor bearing mice. METHOD: S180 tumor-bearing mice model were replicated and divided randomly into 4 groups: the model group, the GFW group, the cyclophosphamide group and the combination administration group. VEGF in serum on each group was detected by ELISA, and the expression of metastasis suppressor gene nm23H1 and cell adhesion molecule CD44 in Sarcoma were detected by SABC immunohistochemical assay. RESULT: Compared with the model group, the GFW group showed a significant decrease in VEGF in serum (P < 0.01). From their statistically significant difference, GFW was proved to promote the expression of metastasis suppressor gene nm23H1 and inhibit the expression of cell adhesion molecule CD44 (P < 0.05). CONCLUSION: GFW has an effect on inhibiting tumor metastasis to some extent. PMID- 22667157 TI - [Study on human UDP-glucuronosyltransferase (UGT) isoforms involved in in vitro metabolism of trans-resveratrol]. AB - OBJECTIVE: To study major human UGT isoforms involved in trans-resveratrol (TR) phase II metabolism. METHOD: trans-resveratrol and 12 major human UGT isoforms were incubated in vitro and then glucuronic acid metabolites were determined by HPLC-MS, in order to preliminarily analyze the structure and observe the effect of different UGT isoforms on the generation rate of glucuronic acid metabolites. RESULT: In in vitro metabolic system, two metabolites-4'-O-monoglucuronide resveratrol (M-1) and 3-0-monoglucuronide resveratrol (M-2)-were generated from trans-resveratrol after being catalyzed by UGT. During the cause, generation of M 1 and M-2 were catalyzed by UGT1A1, UGT1A3, 1A8, 1A9 andlA10, whereas only UGT1A6 and 1A7 contributed to the forma-tion of M-2. Both the formation rate of M-1 and M-2 catalyzed by UGT1A1, 1A10 and the formation of M-2 catalyzed by UGT1A8 slowed down with the increasing concentration of substrates, causing the phenomenon of "substrate inhibition". CONCLUSION: UGT1A1, 1A8, 1A9, 1A10 get involved in the formation of M-1, and of them UGTIA9 is the most important contributor. UGT1A3 also makes small contribution to the formation of M-1 and M-2, while other UGT isoforms show hardly any reaction with the trans-resveratrol phase II metabolites. PMID- 22667158 TI - [Simultaneous determination of isoorientin, scutellarin and cynaroside in rat plasma and pharmacokinetics by UPLC-MS/MS]. AB - OBJECTIVE: To establish a UPLC-MS/MS analysical method for simultaneous determination of concentrations of isoorientin, scutellarin and cynaroside in rat plasma and to study their pharmacokinetic characteristics after intravenous injection of 3 doses of Fufang Hongcao in rats. METHOD: Acidified plasma samples were precipitated for protein with methanol. Waters Acquity BEH C18 column was adopted for spectrum, with mobile phase as 0. 1% formic acid acetonitrile-0. 1% formic acid-water gradient elution. Detection was carried out by the multiple reaction monitoring (MRM) positive ion mode with ESI ionization source. RESULT: Three flavonoids show a good linear relationship, with the extraction recovery ranging between 78.56% and 101.91% and a high intra-and inter-day precisions and accuracy. The MRT of the three flavonoids were all lower than 22 min in rats. CONCLUSION: The above men tioned method is so specific, rapid, sensitive that it is suitable for pharmacokinetic studies of Fufang Hongcao injection in rats. PMID- 22667159 TI - [Sustained efficacy of alpha-interferon therapy combined with Yixuesheng Capsule in treatment of chronic hepatitis B]. AB - OBJECTIVE: To observe the difference between the combination therapy of alpha interferon (IFN-alpha) therapy Yixuesheng Capsule and the monotherapy of IFN alpha in treatment of chronic hepatitis B. METHOD: A total of 288 patients with HBeAg-positive chronic hepatitis B proven by liver biopsy were included in this study. During the individualized therapy, they received hypodermic injection of IFN-alpha 1b, with 5 MU x time(-1) and three times x w(-1). Of them, 125 patients received combination therapy with Yixuesheng Capsule for three months, with 1.0 g/time and three times/d; and 163 patients received only IFN-alpha 1b (the IFN alpha monotherapy group). After the course of therapy, all patients were followed up for at least 24 months. The intention-to-treat analysis was adopted for statistic analysis. RESULT: The two groups showed no statistical significance by gender, age, liver necroinflammation grading, liver fibrosis staging, serum ALT levels, serum HBV DNA levels and IFN-alpha therapy course. The whole course and the 24-month follow-up visit cover all of 112 patients in the combination treatment group and 141 cases in the IFN-alpha monotherapy group. The response rates of the combination treatment group and the IFN-alpha monotherapy group were 48.0% (60/125) and 35.0% (57/163) (x = 4.980, P = 0.026) at the end of treatment, respectively, 45.6% (57/125) and 33.1% (54/163) (x2 = 4.645, P =0.031) at the end of 12-month-follow-up period, respectively, and 38.4% (48/125) and 32.5% (53/163) (x2 = 1.076, P = 0.300) at the end of 24-month follow-up period, respectively. CONCLUSION: The combination treatment with IFN-alpha and Yixuesheng Capsule shows a slightly better sustained efficacy on HBeAg-positive chronic hepatitis B patients compared with IFN-alpha monotherapy. PMID- 22667160 TI - [Study on traditional Chinese medicine prescriptions for cardiovascular diseases over the past 20 years and logistic regression analysis]. AB - OBJECTIVE: To analyze the relationship between TCM's characteristics and treatment of cardiovascular diseases on the basis of the modem medical research literatures about treatment of cardiovascular diseases and establish a mathematic model in order to give reference for clinical study and clinical prescription for treatment of cardiovascular diseases with TCMs. METHOD: Articles on treatment of cardiovascular diseases with TCMs published at home in the past 20 years were collected and screened to summarize the number of TCMs with different function, property, flavor, channel tropism and the number of them with the therapeutically effect on cardiovascular diseases. And a mathematic model was established on the multivariate discriminatory analysis. RESULT: Medicines for activating blood circulation and removing blood stasis (21.21%), those restoring deficiency (17.65%), those attributive to heart channel (21.82%) and those attributive to spleen channel (16. 11%) were relatively active in study for treatment of cardiovascular diseases and showed great difference (P < 0.05). According to findings of the logistic regression screen, TCMs attribute to heart, spleen, gallbladder, pericardium channel and those restoring deficiency were important impact factors with therapeutically effect on cardiovascular diseases (regression coefficient > 0 and P < 0.05). The coincidence was 91.6% between mathematical computing and original classification, indicating the coincidence with relevant theories of the traditional Chinese medical science. CONCLUSION: A more objective Logistic regression equation with a higher accuracy rate of retrospective inspection is established to detect the effect of TCMs with different characteristics on cardiovascular diseases. It is suggested that more experiments and clinical comparative studies on treatment of cardiovascular diseases with TMCs shall be included in pharmacopeia. PMID- 22667161 TI - Policy: The fairness debate will put health back on the front pages. PMID- 22667162 TI - Private sector: Circle needs 70m sterling pounds surpluses to clear debts. PMID- 22667163 TI - Webinar: May the force be with you. PMID- 22667164 TI - Reforms could be the coalition's poll tax. PMID- 22667165 TI - Trouble with troubleshooters. PMID- 22667166 TI - Rescuing innovation. PMID- 22667167 TI - Variation: The winds of change. PMID- 22667168 TI - Peer leaders: New wave of leaders know they cannot go it alone. PMID- 22667169 TI - Innovation: Can you afford to ignore reserch and development? PMID- 22667170 TI - Legal: Confessions of a health worker. PMID- 22667171 TI - Commissioning: Time to come out of the closet. PMID- 22667172 TI - [Stay alert to emerging rabies]. PMID- 22667173 TI - [Finished = finished]. PMID- 22667174 TI - [Jan Vaarten: 'European admission of veterinary drugs is necessary']. PMID- 22667175 TI - [Surveillance]. PMID- 22667176 TI - Copper-associated hepatic cirrhosis in a Friesian horse. AB - A 6-year-old Friesian stallion was examined because of signs of exercise intolerance, stiff gait and symmetrical hind weakness, and increased serum liver enzymes. On presentation, the horse showed muscle atrophy of the hindquarters. Neurological investigation showed no abnormalities. Laboratory findings revealed a prolonged prothrombin time and increased levels of alkaline phosphatase (AF), aspartate aminotransferase (ASAT), gamma-glutamyl-transferase (GGT), lactate dehydrogenase (LDH), and bile acids. Histological evaluation of the liver revealed severe cirrhosis and intracytoplasmic greyish brown granules in almost all hepatocytes, sinusoidal Kuppfer cells, and macrophages. These granules stained strongly for copper. Treatment to slow hepatic fibrosis was advised and included oral prednisolone administration for at least 1 month. A diet to support liver function was formulated by a nutritional specialist, and vitamin E was advised as dietary supplement to support neuromuscular function. Soon after diagnosis, the animal showed signs of intravascular haemolysis, with the presence of Heinz bodies in peripheral blood smears, and haemoglobinuria. On the basis of this haemolytic crisis and the poor prognosis of the chronic hepatic disease, the horse was euthanized at the owners' request. Although we could not establish the cause of the hepatic copper accumulation, this case report highlights that excessive copper in the liver should be considered in the differential diagnosis of hepatic cirrhosis and Heinz body anaemia in the horse. PMID- 22667177 TI - [Flea and tick control in dogs and cats]. AB - Fleas and ticks may cause skin problems in dogs and cats and transmit (zoonotic) diseases. This is an overview about the present situation of the ectoparasites control. PMID- 22667178 TI - [Lipoproteins play an important role in Streptococcus suis recognition]. PMID- 22667179 TI - [Signal function of veterinarians in blue algae poisoning underestimated]. PMID- 22667180 TI - ['One health', also at the defence department]. PMID- 22667181 TI - ['Recognizing emotions when talking about animal welfare']. PMID- 22667183 TI - [Collaborating with animal specialty stores offers opportunity for veterinarians]. PMID- 22667182 TI - [Handling health problems in pedigree dogs start with the buyer]. PMID- 22667184 TI - [Heart abnormalities in the cat, dog and ferret]. PMID- 22667185 TI - [Mebius Kramer, an outstanding administrator]. PMID- 22667186 TI - [CKRD]. PMID- 22667187 TI - [Concrete results in Tanzania]. PMID- 22667188 TI - [I like it!]. PMID- 22667189 TI - [Cone beam-computer tomography in general practice]. PMID- 22667190 TI - [Permanent wire behind the teeth against recurrence of forced teeth have more disadvantages than advantages. Yes]. PMID- 22667191 TI - [Permanent wire behind the teeth against recurrence of forced teeth have more disadvantages than advantages. No]. PMID- 22667192 TI - [Contemplations on responsibility for oral healthcare]. AB - The academic dental education in The Netherlands has been extended to 6 years, among other reasons in order to make it possible for responsibility for oral healthcare to be borne in a wide medical context. It is the job of the 3 national dental schools to make this happen. The new dentist should know and recognize all (peri-)oral disorders and oral symptoms of systemic diseases, and he should be able to deliver oral healthcare to medically compromised patients. Accepting this responsibility is required for dentistry to be transformed into medical oral healthcare and for dentists to be upgraded to oral physicians. PMID- 22667193 TI - [Bacterial meningitis]. AB - Bacterial meningitis is a severe disease which affects 35.000 Europeans each year and has a mortality rate of about 20%. During the past 25 years the epidemiology of bacterial meningitis has changed significantly due to the implementation of vaccination against Haemophilus influenzae, Neisseria meningtidis group C and Streptococcus pneumoniae. Due to these vaccines, meningitis is now predominantly a disease occurring in adults, caused especially by Streptococcus pneumoniae, while it was formerly a child disease which was largely caused by Haemophilus influenzae. Bacterial meningitis is often difficult to recognize since the classical presentation with neck stiffness, reduced awareness and fever occurs in less than half of the patients. The only way to diagnose or exclude bacterial meningitis is by performing low-threshold cerebrospinal fluid examination with a suspicion of bacterial meningitis. The treatment consists of the prescription of antibiotics and dexamethasone. PMID- 22667194 TI - [An abnormal hyoid in a panoramic radiograph]. AB - With ossification of the stylohyoid ligament a diverse spectrum of complaints are possible. A conclusive explanation for the appearance of this ossification has so far not been found. Since treatment is not, in principle, necessary, a policy of observation is often preferred. If complaints persist, physiotherapy, anti inflammatory medication or surgical treatment can be considered. PMID- 22667195 TI - [The oral problems of queen Elizabeth I]. AB - Queen Elizabeth I of England (1533-1603), probably the most famous English Queen ever, had persistent oral problems. Her oral problems were so serious that they probably hampered the Queen in the performance of her tasks. PMID- 22667196 TI - [Referral of patients with non-odontogenic oral diseases to an oral and maxillofacial surgeon]. AB - Patients with non-odontogenic oral diseases may be referred to an oral and maxillofacial surgeon by a dentist, a general medical practitioner or a medical specialist. At the department of Oral and Maxillofacial Surgery of a medical centre, a survey involving 96 referred patients with a non-odontogenic oral disease addressed the clinician who was responsible for the referral, the patient characteristics, and the nature and location of the oral disease. From the patients who regularly visited a dentist, 53% were referred by a dentist. From the patients who visited a dentist irregularly, 73% were referred by a general medical practitioner. No significant correlation was found between the nature and location of the non-odontogenic oral disease and the profession of the clinician who was responsible for the referral, with an exception for the tongue, for which a medical specialist was more often responsible for the referral. PMID- 22667199 TI - Academic science marketing. PMID- 22667197 TI - [Dissertations 25 years after date 33. Developments in apical surgery]. AB - Twenty five years ago patients with unsuccessful root canal treatments and complaints about pain were generally referred directly to an oral surgeon for apical surgery. Since then, much has changed in the treatment of these difficult or failed endodontic treatments. First, from 1996 it became financially attractive for the general practitioner to carry out root canal treatments because remuneration for them was more in keeping with their worth after the national health system disappeared in the Netherlands (in 1996). A second important development was the appearance of the dentist-endodontologist as a distinct oral healthcare professional who, due to his greater knowledge and improved technology is able to carry out corrective treatment on unsuccessful root canal treatments in a non-surgical way with a good chance of healing. PMID- 22667198 TI - Periodic trends in lanthanide and actinide phosphonates: discontinuity between plutonium and americium. AB - The hydrothermal reactions of trivalent lanthanide and actinide chlorides with 1,2-methylenediphosphonic acid (C1P2) in the presence of NaOH or NaNO(3) result in the crystallization of three structure types: RE[CH(2)(PO(3)H(0.5))(2)] (RE = La, Ce, Pr, Nd, Sm; Pu) (A type), NaRE(H(2)O)[CH(2)(PO(3))(2)] (RE = La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy; Am) (B type), or NaLn[CH(2)(PO(3)H(0.5))(2)].(H(2)O) (Ln = Yb and Lu) (C type). These crystals were analyzed using single crystal X-ray diffraction, and the structures were used directly for detailed bonding calculations. These phases form three-dimensional frameworks. In both A and B, the metal centers are found in REO(8) polyhedra as parts of edge-sharing chains or edge-sharing dimers, respectively. Polyhedron shape calculations reveal that A favors a D(2d) dodecahedron while B adopts a C(2v) geometry. In C, Yb and Lu only form isolated MO(6) octahedra. Such differences in terms of structure topology and coordination geometry are discussed in detail to reveal periodic deviations between the lanthanide and actinide series. Absorption spectra for the Pu(III) and Am(III) compounds are also reported. Electronic structure calculations with multireference methods, CASSCF, and density functional theory, DFT, reveal localization of the An 5f orbitals, but natural bond orbital and natural population analyses at the DFT level illustrate unique occupancy of the An 6d orbitals, as well as larger occupancy of the Pu 5f orbitals compared to the Am 5f orbitals. PMID- 22667200 TI - ACS Software. PMID- 22667202 TI - Address Change for ES&T Manuscript. PMID- 22667203 TI - Industry's Future: Changing Patterns of Industrial Research. PMID- 22667204 TI - Radiation and public perception. PMID- 22667205 TI - Rhizosphere effects. PMID- 22667206 TI - Hexavalent chromium. PMID- 22667208 TI - Distinguishing between recent and past oil spills. PMID- 22667207 TI - Dechlorinating TCDD. PMID- 22667209 TI - Microwave extraction. PMID- 22667210 TI - White rot fungi and PCBs. PMID- 22667211 TI - Benign by design: alternative synthetic design for pollution prevention. PMID- 22667212 TI - Mercury in lakes. PMID- 22667213 TI - Toxicity test errors. PMID- 22667215 TI - Using iron amendment to immobilize selenium. PMID- 22667214 TI - Maintaining biodiversity. PMID- 22667216 TI - Exploring QSAR. PMID- 22667217 TI - Potency estimates. PMID- 22667219 TI - Ecological and human risk. PMID- 22667218 TI - Zebra mussel control. PMID- 22667220 TI - Organics sorption to soils. PMID- 22667221 TI - Laboratory accreditation program update. PMID- 22667222 TI - Ozone precursors trading guidance proposed. PMID- 22667223 TI - Proposed SW-846 methods. PMID- 22667224 TI - Free Enrollment in ACS Short Courses for Unemployed Members. PMID- 22667225 TI - MACT averaging allowed for petroleum refineries. PMID- 22667226 TI - Local brownfields pilot projects funded. PMID- 22667227 TI - Environmental justice moves to enforcement. PMID- 22667228 TI - SAB to include "lookout panel" in risk redux. PMID- 22667229 TI - Stay ahead of the curve. PMID- 22667230 TI - New criteria to be used in identifying human carcinogens. PMID- 22667232 TI - EPA particulate matter health effects document criticized. PMID- 22667231 TI - Mechanistic criteria cut two ways. PMID- 22667234 TI - More bad news for triazine herbicides. PMID- 22667233 TI - Atrazine found to cause chromosomal breaks. PMID- 22667235 TI - Do microbes contribute to sick building syndrome? PMID- 22667236 TI - Automated environmental laboratory unveiled at Los Alamos. PMID- 22667237 TI - "Lasagna process" field success increases DOE's interest. PMID- 22667238 TI - 1995 may be high-ozone year in U.S., early data indicate. PMID- 22667239 TI - Unexpected ozone lows in L.A. PMID- 22667240 TI - Management limitations hurting DOE cleanups, panel told. PMID- 22667241 TI - Acid rain program report cites successes. PMID- 22667243 TI - Unified environmental statute concept gains support. PMID- 22667242 TI - International environmental management standard advances. PMID- 22667244 TI - Briefs. PMID- 22667245 TI - ES&T Information Express. PMID- 22667246 TI - Building a national water quality monitoring program. PMID- 22667247 TI - "Scientific uncertainty" scuttles new Acid rain standard. PMID- 22667249 TI - Chemistry from a different perspective. PMID- 22667248 TI - Europeans developing "critical load" standards. PMID- 22667250 TI - Subjective judgments by climate experts. PMID- 22667251 TI - Analytical products. PMID- 22667253 TI - Classified sectauion. PMID- 22667254 TI - PROFESSIONAL CONSULTANTS SERVICES DlRECTORY. PMID- 22667256 TI - Contralateral hearing aid use in cochlear implanted patients: multicenter study of bimodal benefit. AB - CONCLUSION: The use of a hearing aid (HA) in combination with a cochlear implant (CI) significantly improved performance for speech perception in quiet, in noise, and for localization compared with monaural conditions. No significant differences in functional performance were observed following optimization of HA fitting. OBJECTIVES: To evaluate the binaural benefits derived from using a contralateral HA in conjunction with a CI in subjects with significant functional hearing in the nonimplanted ear and the effects of HA fitting optimization. METHODS: Fifteen adult CI users, intra-subject controls, were enrolled in a prospective repeated-measure multicenter study. Evaluation of performance for speech understanding, localization, and subjective impressions was conducted before and following HA fitting optimization for CI alone, HA alone, and CI + HA. RESULTS: For speech testing in quiet, bimodal scores were significantly better than for HA alone and CI alone conditions (p < 0.01). For speech and noise (S0N0) at 0 degrees azimuth the scores were significantly better in the bimodal condition than for CI alone (p = 0.01), indicating binaural summation. When noise was presented to the HA side (S0NHA) bimodal scores were significantly better than for CI alone (p < 0.01 and p < 0.05, respectively), suggesting a significant binaural squelch effect. Sound localization ability was significantly improved in the bimodal condition compared with the CI alone condition (p = 0.002). PMID- 22667257 TI - Comment on "Direct observation of tetrahedrally coordinated Fe(III) in ferrihydrite". PMID- 22667321 TI - Ultrafast Kikuchi diffraction: nanoscale stress-strain dynamics of wave-guiding structures. AB - Complex structural dynamics at the nanoscale requires sufficiently small probes to be visualized. In conventional imaging using electron microscopy, the dimension of the probe is large enough to cause averaging over the structures present. However, by converging ultrafast electron bunches, it is possible to select a single nanoscale structure and study the dynamics, either in the image or using electron diffraction. Moreover, the span of incident wave vectors in a convergent beam enables sensitivity levels and information contents beyond those of parallel-beam illumination with a single wave vector Bragg diffraction. Here, we report the observation of propagating strain waves using ultrafast Kikuchi diffraction from nanoscale volumes within a wedge-shaped silicon single crystal. It is found that the heterogeneity of the strain in the lateral direction is only 100 nm. The transient elastic wave gives rise to a coherent oscillation with a period of 30 ps and with an envelope that has a width of 140 ps. The origin of this elastic deformation is theoretically examined using finite element analysis; it is identified as propagating shear waves. The wedge-shaped structure, unlike parallel-plate structure, is the key behind the traveling nature of the waves as its angle permits "transverse" propagation; the parallel-plate structure only exhibits the "longitudinal" motion. The studies reported suggest extension to a range of applications for nanostructures of different shapes and for exploring their ultrafast eigen-modes of stress-strain profiles. PMID- 22667322 TI - Fluorescent C-linked C8-aryl-guanine probe for distinguishing syn from anti structures in duplex DNA. AB - The synthesis and optical properties of the carbon (C)-linked C(8)-(2" benzo[b]thienyl)-2'-deoxyguanosine ((Bth)dG), which acts as a fluorescent reporter of syn versus anti glycosidic conformations in duplex DNA, are described. In the syn-conformation, the probe stabilizes a G:G mismatch, emits at ~385 nm (excitation ~285 nm), and shows an induced circular dichroism (ICD) signal at ~320 nm. Molecular dynamics (MD) simulations predict a wedge (W) conformation for the mismatched duplex with the C(8)-benzo[b]thienyl moiety residing in the minor groove. In contrast, the probe destabilizes the duplex when base paired with its normal pyrimidine partner C. With flanking purine bases, a major groove B-type duplex is favored with (Bth)dG present in the anti conformation emitting at ~413 nm (excitation ~326 nm) and no ICD signal. However, with flanking pyrimidine bases, (Bth)dG adopts the syn-conformation when base paired with C, and MD simulations predict a base-displaced stacked (S) conformation, with the opposing C flipped out of the helix. The different duplex (B-, S-, and W-) conformers formed upon incorporation of (Bth)dG are known to play a critical role in the biological activity of N-linked C8-dG adducts formed by arylamine carcinogens. Bulky environment-sensitive fluorescent C(8)-dG adducts that mimic the duplex structures formed by carcinogens may be useful in luminescence-based DNA polymerase assays. PMID- 22667323 TI - Dense coordination network capable of selective CO2 capture from C1 and C2 hydrocarbons. AB - We elucidated the specific adsorption property of CO(2) for a densely interpenetrated coordination polymer which was a nonporous structure and observed gas separation properties of CO(2) over CH(4), C(2)H(4), and C(2)H(6), studied under both equilibrium and kinetic conditions of gases at ambient temperature and pressure. PMID- 22667324 TI - Engineering folate-drug conjugates to target cancer: from chemistry to clinic. AB - The folate receptor (FR) is a potentially useful biological target for the management of many human cancers. This membrane protein binds extracellular folates with very high affinity and, through an endocytic process, physically delivers them inside the cell for biological consumption. There are now many examples of how this physiological system can be exploited for the targeted delivery of biologically active molecules to cancer. In fact, strong preclinical as well as emerging clinical evidence exists showing how FR-positive cancers can be (i) anatomically identified using folate conjugates of radiodiagnostic imaging agents and (ii) effectively treated with companion folate-targeted chemotherapies. While the biological results are compelling, it is of equal importance to understand the conjugation chemistries that were developed to produce these active molecules. Therefore, this review will focus on the methods utilized to construct folate-based small-molecule drug conjugates (SMDCs), with particular attention focused on modular design, hydrophilic spacers, and self immolative linkers. PMID- 22667325 TI - Vandetanib for the treatment of lung cancer. AB - INTRODUCTION: VEGF and EGFR are validated pathways for targeted therapy in non small cell lung cancer (NSCLC). Once considered to be separate targets, VEGF and EGFR are now shown to have interconnected downstream pathways, potentiating the effectiveness of their dual signaling inhibition in cancer therapy. Molecules such as vandetanib that inhibit VEGFR and EGFR have also been reported to inhibit other receptors, including RET and additional kinases, and may be beneficial in treating patients with solid tumors. AREAS COVERED: This review covers the significance of targeting VEGF and EGFR in the treatment of NSCLC and the rationale behind their dual inhibition. Clinical trials that evaluate the use of vandetanib in the setting of refractory NSCLC are also explored. EXPERT OPINION: Vandetanib is currently not approved in the setting of NSCLC. However, its approval for medullary thyroid cancer makes it promising for identifying markers and potentially a NSCLC patient population who will benefit from the treatment. PMID- 22667326 TI - Evaluation of pain in intravitreal bevacizumab injections. AB - PURPOSE: To evaluate the correlation between pain associated with intravitreal bevacizumab injection and the location of the injection. METHODS: The study included 218 eyes of 218 patients, who received an intravitreal bevacizumab injection at our institution. Pain was measured by the Visual Analog Scale (VAS). Additional parameters recorded included age, sex, indication for the injection, injection site by quadrant, number injections in the study eye, presence of diabetes mellitus, and lens status. RESULTS: Indications for injection included age-related macular degeneration (69.7%), diabetic macular edema (13.3%), neovascularization due to proliferative diabetic retinopathy (6.9%), and cystoid macular edema secondary to retinal vascular occlusions (10.1%). Pain scores on the VAS ranged from 0 to 84, with a mean of 17.4 +/- 17.1. Pain did not correlate significantly with any of the recorded parameters, but a trend was found toward less pain associated with injection in the lower-left quadrant (p = 0.067). CONCLUSIONS: This is the largest series studying the pain associated with intravitreal injections and provides a thorough description of the pain associated with this procedure. Since there is no anatomical difference between quadrants, we assume the demonstrated trend indicates that less pain is associated with the location in which it is most convenient for the ophthalmologist to perform the injection. PMID- 22667328 TI - Effects of hyperbaric oxygen on crystalline lens and retina in nicotine-exposed rats. AB - OBJECTIVE: To determine histopathological changes on crystalline lens and retina of rats after subcutaneous injection of nicotine and to examine the effects of hyperbaric oxygen (HBO) on these changes related to nicotine exposure. METHODS: Twenty-eight female Sprague-Dawley rats were enrolled in the study and the rats were divided into four equal sized groups randomly (Group N: the rats exposed only to nicotine, group HB: the rats received only HBO, group N+HB: the rats that underwent to nicotine injection and subsequently received HBO, group C: the control group that neither exposed to nicotine nor received HBO). The rats were sacrificed by decapitation method and all were enucleated immediately after scarification. Tissue samples from crystalline lens, lens capsule, and the retina from the right eyes of the rats were examined by light microscopy. RESULTS: While the histological appearances of the retina and the lens was similar in group HB, group N+HB, and the control group; group N showed some pathological changes like decrement in the retinal ganglion cell density, atrophy of the retinal nerve fiber layer, congestion of the vessels in the optic nerve head, thinning of the internal plexiform layer, thinning of the lens capsule, and transformation of the anterior subcapsular epithelium into squamous epithelia. DISCUSSION: Subcutaneous injection of nicotine was found to be related with some pathological changes in the retina and lens of the Sprague-Dawley rats. However HBO caused no significant negative effect. Furthermore, the histopathological changes related to nicotine exposure in the lens and retina of the rats recovered by the application of HBO. PMID- 22667327 TI - A second allosteric site in Escherichia coli aspartate transcarbamoylase. AB - Escherichia coli aspartate transcarbamoylase is feedback inhibited by CTP and UTP in the presence of CTP. Here, we show by X-ray crystallography that UTP binds to a unique site on each regulatory chain of the enzyme that is near but not overlapping with the known CTP site. These results bring into question all of the previously proposed mechanisms of allosteric regulation in aspartate transcarbamoylase. PMID- 22667329 TI - Radical one-pot alpha,beta-dual and beta-mono-oxymethylation of alkylidenemalonate. AB - Dimethylzinc-mediated radical conjugate addition reaction of dimethyl alkylidenemalonates with iodomethyl pivalate gave a high yield of the alpha,beta dual oxymethylation product in one pot under air and the beta pivaloyloxymethylation product under argon. PMID- 22667330 TI - Anti-selective direct catalytic asymmetric aldol reaction of thiolactams. AB - An anti-selective direct catalytic asymmetric aldol reaction of thiolactam is described. A soft Lewis acid/hard Bronsted base cooperative catalyst comprised of mesitylcopper/(R,R)-Ph-BPE exhibited high catalytic performance to produce an anti-aldol product with high stereoselectivity. The highly chemoselective nature of the present catalysis allows for the use of enolizable aldehydes as aldol acceptors. The diverse transformations of the thiolactam moiety highlight the synthetic utility of the present anti-aldol protocol. PMID- 22667332 TI - Fluorescence lifetimes and quantum yields of rhodamine derivatives: new insights from theory and experiment. AB - Although lifetimes and quantum yields of widely used fluorophores are often largely characterized, a systematic approach providing a rationale of their photophysical behavior on a quantitative basis is still a challenging goal. Here we combine methods rooted in the time-dependent density functional theory and fluorescence lifetime imaging microscopy to accurately determine and analyze fluorescence signatures (lifetime, quantum yield, and band peaks) of several commonly used rhodamine and pyronin dyes. We show that the radiative lifetime of rhodamines can be correlated to the charge transfer from the phenyl toward the xanthene moiety occurring upon the S(0) <- S(1) de-excitation, and to the xanthene/phenyl relative orientation assumed in the S(1) minimum structure, which in turn is variable upon the amino and the phenyl substituents. These findings encourage the synergy of experiment and theory as unique tool to design finely tuned fluorescent probes, such those conceived for modern optical sensors. PMID- 22667333 TI - Design of a universal reversible bidirectional current switch based on the fullerene-phthalocyanine supramolecular system. AB - A novel bidirectional current ON-OFF switch controlled by electron injection and deprivation was proposed on the basis of the density functional theory (DFT) calculation over a fullerene-phthalocyanine supramolecular system PcCoC(60) for the first time. The electron density for PcCoC(60) was revealed to move from fullerene to phthlocyanine only in the oxidized form and from phthlocyanine to fullerene only in the reduced form, reaching the control of electron movement direction by changing the oxidation state of this supramolecular system. PMID- 22667334 TI - Clinicopathological characteristics of extramedullary acute megakaryoblastic leukemia (AMKL): report of a case with initial mastoid presentation and review of literature to compare extramedullary AMKL and non-AMKL cases. AB - Extramedullary acute megakaryoblastic leukemia (AMKL) is a rare neoplasm with a varied clinical presentation. AMKL with initial mastoid presentation has never been reported. The extreme rarity of mastoid AMKL, together with the tendency of extramedullary AMKL to mimic other small blue cell tumors, can create a diagnostic challenge. We report a case of AMKL that initially presented as a mastoid lesion and provide a comprehensive review and analysis that compares the characteristics of extramedullary AMKL and nonmegakaryoblastic acute myeloid leukemia (AML) in reported pediatric cases over the past 30 years. We found that patients with extramedullary AMKL were not only younger than patients without megakaryocytic differentiation but were also limited to those <= 2 years of age. In addition, girls predominated in both AMKL and AML MLL(+) groups compared with other types of AML (P = 0.0366 and P = 0.0082). Furthermore, we found that extramedullary AMKL was more likely to involve bone than AML MLL(+) (P < 0.0001) or other types of AML (P = 0.0002). These findings suggest that extramedullary AMKL should be considered in the differential diagnosis of SBCT in children, especially in patients with mastoid or other bony lesions, those <= 2 years of age, and female patients. PMID- 22667335 TI - Perilipin family (PLIN) proteins in human skeletal muscle: the effect of sex, obesity, and endurance training. AB - Proteins that coat the lipid droplets (also known as PAT proteins or perilipin (PLIN) family proteins) have diverse functions that are not well elucidated in many tissues. In skeletal muscle, there is even less known about the functions or characteristics of these proteins or how they might change in response to perturbations that alter both intramyocellular lipid (IMCL) content and fat utilization and oxidation. Therefore, the purpose of this study was to examine the human muscle content and gene expression of the four skeletal muscle PLIN proteins in both lean and obese men and women and how this was changed following a 12-week endurance training protocol. PLIN2-PLIN5 proteins were all more abundant in women than in men (p = 0.037 and p < 0.0001, respectively), consistent with higher IMCL content observed in female skeletal muscle. PLIN5 (previously known as OXPAT) is of particular interest because it has previously been associated primarily with oxidative tissues that rely heavily on fat oxidation for energy production. Although PLIN5 was not different between lean and obese subjects, it was the only PLIN protein to increase in response to endurance training in both sexes. PLIN5 correlated with IMCL volume (p < 0.0001), but in general, the other PLIN proteins did not correlate well with IMCL volume, suggesting that the relationship between lipid accumulation and PLIN family protein content is not a simple one. Although more work is necessary, it is clear that PLIN5 likely plays an important role in IMCL accumulation and oxidation, both of which increase with endurance training in human skeletal muscle. PMID- 22667336 TI - Polyphenon E 10% ointment: in immunocompetent adults with external genital and perianal warts. AB - Polyphenon E 10% ointment, which contains a mixture of green tea catechins, is indicated for the treatment of external genital and perianal warts (Condylomata acuminata) in immunocompetent patients aged >=18 years. In two double-blind, multinational studies in adults with external genital and perianal warts, polyphenon E 10% ointment for up to 16 weeks was significantly more effective than vehicle with regard to the complete clearance of all warts (i.e. those at baseline and newly appearing during treatment) [primary endpoint]. In gender subgroup analyses, polyphenon E 10% ointment was more effective than vehicle in both men and women in one of two individual studies, and in pooled data from both studies. Polyphenon E 10% ointment was also significantly more effective than vehicle with regard to several secondary endpoints, including the complete clearance of baseline warts and partial clearance of at least 50% of all warts in both studies. Rates of recurrence of any warts or development of new warts were low (<9%) in both treatment arms during a 12-week follow-up period in both studies. Polyphenon E 10% ointment was generally well tolerated in adults with external genital and perianal warts. According to pooled data from the two clinical studies, the majority of adverse events associated with polyphenon E 10% ointment involved application site and local skin reactions at the treatment site. PMID- 22667337 TI - Childhood leukemia and its impact on graduation and having children: results from a national survey. AB - To assess the level of graduation, the wish to have children and the course of pregnancy among former patients with childhood leukemia in comparison to the general German population and depending on gender, a nationwide survey was conducted in 2008. In total 63.6% (1476/2319) of the contacted survivors of childhood leukemia participated (mean age 25.7 years, range 19-43 years). Survivors graduated at higher levels of school compared to the general population, with 48.6% (female) versus 38.0% and 52.6% (male) versus 35.8% (p < 0.001). Also, 93.3% of female and 89.3% of male survivors indicated a similar general wish to have children compared to the general population. Survivors reported parenthood less frequently compared to the general population (p < 0.001). The course of pregnancy in survivors was characterized by fewer abortions (p < 0.001). Having leukemia in childhood and adolescence impairs the likelihood of becoming a parent but reduces neither the wish to have children nor the level of graduation. PMID- 22667338 TI - Characterization of side population (SP) cells in murine cochlear nucleus. AB - CONCLUSION: We characterized side population (SP) cells in the cochlear nucleus (CN). Some genes of stem/progenitor markers in sorted SP cells were identified by microarray analysis and RT-PCR. Furthermore, some cells in the CN also demonstrated self-renewal and clonal expansion activities. These results suggest that tissue stem/ progenitor like cells would be identified and characterized as a slow cycling and immaturity in SP cells of CN. OBJECTIVES: SP cells were sorted and characterized as regards their activity in the CN in order to identify the tissue progenitor/stem cells in the auditory nervous system. METHODS: Bromodeoxyuridine (BrdU)-injected mice were prepared and the long-term BrdU retaining cells were detected by flow cytometry. Gene expression of SP and MP cells was analyzed by microarray analysis and RT-PCR. SP cells were cultured in conditioned medium to expand stem/progenitor cells in vitro and to estimate the spheroid-forming activity of stem cells. RESULTS: In all, 1% of cells in the CN were detected as BrdU-positive. SP cells were detected at a frequency of 4.4% and expressed stem/progenitor markers, Abcb1b, Abcg2, Sca1, Notch1, Notch4, Hes1, and Jag1 in microarray analysis. Expression of Abcb1b, Abcg2, Sca1,Oct3/4, and Sox2 as determined by RT-PCR was supported by the microarray data. CN cells also had sphere-forming activity in young mice, but this activity was decreased by aging. PMID- 22667340 TI - Transforming growth factor beta 1 genotype and p16 as prognostic factors in head and neck squamous cell carcinoma. AB - CONCLUSION: Transforming growth factor beta1 gene (TGFbeta1) genotype is a potential p16 independent prognostic factor predicting response to chemoradiotherapy in head and neck squamous cell carcinoma (HNSCC). OBJECTIVES: Expression of p16 and epidermal growth factor receptor (EGFR) has been reported to be associated with survival in HNSCC. We have previously reported that genetic polymorphism of TGFbeta1 is linked with survival in HNSCC patients who have undergone chemoradiotherapy. We evaluate here whether TGFB1 genotype can serve as a prognostic factor independent of tumor p16 and EGFR expression. METHODS: Expression of p16 and EGFR was studied by immunohistochemistry in tumors from 130 HNSCC patients. Peripheral blood DNA was used to genotype 95 patients for single nucleotide polymorphism rs1800470 within the TGFbeta1 gene. The minimum follow-up time was 31 months. RESULTS: p16 overexpression was associated with an improved disease-free survival (hazard ratio (HR) = 0.39, 95% CI 0.19-0.78), whereas no evident association was observed between EGFR expression and disease-free survival (HR = 0.90, 95% CI 0.68-1.19). Among the 37 patients who had received chemoradiotherapy, TGFbeta1 genotype was associated with disease-free (HR = 0.44, 95% CI 0.19-1.02) and overall survival (HR = 0.31, 95% CI 0.12-0.80) independent of tumor p16 expression. PMID- 22667341 TI - Macrophage, mast cell and T lymphocyte infiltrations are independent predictive biomarkers of primary refractoriness or early relapse in classical Hodgkin lymphoma. AB - Tumor-associated macrophages (TAMs) might be associated with worse outcome in classical Hodgkin lymphoma (cHL). Our aim was to determine whether TAMs correlated with refractoriness in cHL. In a cohort of 18 consecutive primary refractory or early relapsed cases and 41 randomly selected controls (responder patients), high TAM infiltration was significantly associated with refractoriness or early relapse (p = 0.004) and remained independently correlated with outcome in multivariate analysis (odds ratio 8.276, 95% confidence interval 1.214 56.408). This study provides evidence that the marker CD68 might accurately predict early outcome of de novo cHL and could be used in combination with c-kit and TiA1 staining. PMID- 22667342 TI - Towards a perfect vehicle(s) for diagnostic patch testing: an overview. AB - The correct selection of vehicles for patch testing is crucial in evaluating suspected allergic contact dermatitis. We reviewed literature by searching Pubmed and Embase for the years 1971-2011 utilizing the subjects "vehicle," "allergic contact dermatitis" and "patch test" for advances in knowledge of vehicles." A universal optimal vehicle more efficient than petrolatum remains undiscovered. Literature provides research supporting alternate vehicles for specific allergens and insights on vehicle characteristics, such as influence on bioavailability of chemicals and subsequent percutaneous absorption or interaction with allergens. These findings should accelerate our ability to define, and thus determine, the optimum vehicle(s). PMID- 22667343 TI - Immunohistochemical study of cyclooxygenase-2 in skin tumors. AB - INTRODUCTION: Anti-cancerous effects of cyclooxygenase-2 (COX-2) inhibitors have been reported in different cancers. High expression of COX-2 has been demonstrated in various neoplasms such as colorectal, gastric, esophageal, breast, non-small cell lung cancers, and pre-neoplastic lesions such as colorectal adenomas and Barrett's esophagus. GOAL: The purpose of this study was to investigate percentage of positive COX-2 expression in skin tumors, including pre-malignant and malignant tumors. METHODS: This is an analytic cross-sectional study that includes 62 skin tumor samples, among which 49 samples were malignant and 13 were pre-malignant. After study for determination of pathologic kind of tumors, samples underwent immunohistochemical study for COX-2 expression. The DakoCytomation EnVision+System-HRP is a two-step extremely sensitive IHC staining technique which we used in this study. RESULTS: Among the skin tumors, a considerable number of COX-2 expression were found in squamous cell carcinomas (SCC) (16 of 17; 94%), basal cell carcinomas (BCC) (28 of 32; 87.5%), Bowen's disease (BD) (8 of 9; 89%), and actinic keratosis (AK) (4 of 4; 100%). CONCLUSION: COX-2 expression was positive in skin tumors including malignant and pre-malignant skin lesions. This study strongly suggests that COX-2 can be one of the molecular targets in treating various skin tumors. PMID- 22667345 TI - The epidemiology of chemical eye injuries. AB - PURPOSE: To describe the epidemiology and identify categories of agents involved in chemical eye injuries. METHODS: Retrospective case series of consecutive cases of chemical eye injury presenting to the emergency department (ED) at a large eye hospital. Six-hundred and thirty-three patients presented to the ED between January 1, 2006 and December 31, 2009 for treatment of 640 chemical eye injuries. Information was collected via medical record review and chemical agents were classified into logical categories based on the patient-reported intended use of the product. Demographic measures, month of service, work-related status, and visual acuity at presentation were described overall and by chemical agent category. RESULTS: Males were more often observed than females (58.4% vs. 41.6%). The mean age across all categories was 33.6 years. More injuries were observed in warmer months. The mean visual acuity for all available injured eyes was 0.17 logarithm of the minimum angle of resolution (20/30 Snellen). The most common categories of chemical agents were cleaning agents, personal care products, and automotive chemicals. Thirty-nine cases were observed as having misidentified a product which led to injury. CONCLUSION: Patterns of eye trauma resulting from chemicals differ by gender, across age groups, and during different months of the year. In most cases, chemical eye injuries do not threaten sight. Improvements in product labeling and design could represent an avenue to prevent some chemical eye injuries. PMID- 22667344 TI - Clinical, pathologic, and functional outcomes after nephron-sparing surgery in patients with a solitary kidney: a multicenter experience. AB - BACKGROUND AND PURPOSE: Surgical management of a renal neoplasm in a solitary kidney is a balance between oncologic control and preservation of renal function. We analyzed patients with a renal mass in a solitary kidney undergoing nephron sparing procedures to determine perioperative, oncologic, and renal functional outcomes. PATIENTS AND METHODS: A multicenter study was performed from 12 institutions. All patients with a functional or anatomic solitary kidney who underwent nephron-sparing surgery for one or more renal masses were included. Tumor size, complications, and recurrence rates were recorded. Renal function was assessed with serum creatinine level and estimated glomerular filtration rate. RESULTS: Ninety-eight patients underwent 105 ablations, and 100 patients underwent partial nephrectomy (PN). Preoperative estimated glomerular filtration rate (eGFR) was similar between the groups. Tumors managed with PN were significantly larger than those managed with ablation (P<0.001). Ablations were associated with a lower overall complication rate (9.5% vs 24%, P=0.01) and higher local recurrence rate (6.7% vs 3%, P=0.04). Eighty-four patients had a preoperative eGFR >=60 mL/min/1.73 m(2). Among these patients, 19 (23%) fell below this threshold after 3 months and 15 (18%) at 12 months. Postoperatively, there was no significant difference in eGFR between the groups. CONCLUSIONS: Extirpation and ablation are both reasonable options for treatment. Ablation is more minimally invasive, albeit with higher recurrence rates compared with PN. Postoperative renal function is similar in both groups and is not affected by surgical approach. PMID- 22667346 TI - An alternative procedure for cochlear implantation: transcanal approach. AB - CONCLUSION: The transcanal approach could be an effective and time-saving method for selected cochlear implantation (CI) candidates. OBJECTIVE: This study was designed to introduce the method of CI via the transcanal approach used in patients with abnormal temporal bone structure or chronic otitis media (COM). METHODS: The medical records of six patients who underwent CI via the transcanal approach were reviewed retrospectively. The electrode was inserted through the external auditory canal (EAC) after tympanomeatal flap elevation and cochleostomy. RESULTS: Three patients had a history of inactive COM. In the remaining patients, cochleostomy via the transmastoid approach was difficult due to aberrant anatomic structures such as vascular anomaly, narrow aditus, and anteriorly displaced sigmoid sinus. All patients underwent CI via the transcanal approach successfully. There was no serious complication postoperatively. PMID- 22667347 TI - An exploratory study of sodium, potassium, and fluid nutrition status of tube-fed nonambulatory children with severe cerebral palsy. AB - Children with severe cerebral palsy (CP) often have lower mineral intakes than healthy children. It is unknown if their lower nutrient intakes are adequate to meet their needs. The objective of this study was to examine the sodium, potassium, phosphate, and fluid status of primarily tube-fed nonambulatory children with severe CP. The design consisted of a cross-sectional exploratory study and a clinical trial of sodium supplementation. Nutritional status was determined among primarily tube-fed children (aged 2 to 17 years) with CP based on blood and urine samples, anthropometry, and 3-day food records. Mineral and fluid status was evaluated by a nephrologist blind to nutrient intakes. Twenty children supplied food records, blood samples, and anthropometric measurements, and 16 supplied urine samples. Six (37.5%) of those who provided urine samples were considered possibly dehydrated, as urine osmolality was >600 mmol.kg(-1). Six (60%) of the 10 children with satisfactory fluid status (low urine osmolality) were considered to have a possible dietary sodium deficiency based on a very low urine sodium concentration (<20 mmol.L(-1)). Those considered to have a possible dietary sodium deficiency had a significantly lower sodium intake (48% +/- 15% Adequate Intake (AI)) compared with those considered sodium sufficient (73% +/- 20% AI) (p = 0.031). One child was considered possibly phosphorus deficient, but none was assessed as likely potassium deficient. The conclusion was that sodium deficiencies were likely prevalent among the children. The findings from this small observational study suggest that sodium intakes for tube fed children with CP should be maintained near the AI for their age. Hydration status of children receiving hypercaloric formulas should be monitored. PMID- 22667348 TI - Addictive behavior among young people in Ukraine: a pilot study. AB - The AUDIT-like tests system was created for complex assessment and evaluation of the addictive status of adolescents in a Ukrainian population. The AUDIT-like tests system has been created from the Alcohol Use Disorders Identification Test (AUDIT) developed by the World Health Organization. The AUDIT-like tests were minimally modified from the original AUDIT. Attention was brought to similarities between stages of different addictions (TV, computer games, the Internet, etc.) and alcohol addiction. Seventeen AUDIT-like tests were created to detect the different types of chemical and non-chemical addictions. PMID- 22667349 TI - Enhanced reactive adsorption of hydrogen sulfide on the composites of graphene/graphite oxide with copper (hydr)oxychlorides. AB - Composites of copper (hydr)oxychlorides with graphite oxide or graphene were synthesized and used as adsorbents of hydrogen sulfide at dynamic conditions at ambient temperatures. The materials were extensively characterized before and after adsorption in order to link their performance to the surface features. X ray diffraction, FTIR, thermal analysis, TEM, SEM/EDX, and adsorption of nitrogen were used. It was found that the composite with graphene has the most favorable surface features enhancing reactive adsorption of hydrogen sulfide. The presence of moisture in the H2S stream has a positive effect on the removal process owing to the dissociation process. H2S is retained on the surface via a direct replacement of OH groups and via acid-base reactions with the copper (hydr)oxide. Highly dispersed reduced copper species on the surface of the composite with graphene enhance activation of oxygen and cause formation of sulfites and sulfates. Higher conductivity of the graphene phase than that of graphite oxide helps in electron transfer in redox reactions. PMID- 22667353 TI - Nona-coordinated chiral Eu(III) complexes with stereoselective ligand-ligand noncovalent interactions for enhanced circularly polarized luminescence. AB - Circularly polarized luminescence (CPL) of chiral Eu(III) complexes with nona- and octa-coordinated structures, [Eu(R/S-iPr-Pybox)(D-facam)(3)] (1-R/1-S; R/S iPr-Pybox, 2,6-bis(4R/4S-isopropyl-2-oxazolin-2-yl)pyridine; D-facam, 3 trifluoroacetyl-d-camphor), [Eu(S,S-Me-Ph-Pybox)(D-facam)(3)] (2-SS; S,S-Me-Ph Pybox, 2,6-bis(4S-methyl-5S-phenyl-2-oxazolin-2-yl)pyridine), and [Eu(Phen)(D facam)(3)] (3; Phen, 1,10-phenanthroline) are reported, and their structural features are discussed on the basis of X-ray crystallographic analyses. These chiral Eu(III) complexes showed relatively intense photoluminescence due to their (5)D(0) -> (7)F(1) (magnetic-dipole) and (5)D(0) -> (7)F(2) (electric-dipole) transition. The dissymmetry factors of CPL (g(CPL)) at the former band of 1-R and 1-S were as large as -1.0 and -0.8, respectively, while the g(CPL) of 3 at the (5)D(0) -> (7)F(1) transition was relatively small (g(CPL) = -0.46). X-ray crystallographic data indicated specific ligand-ligand hydrogen bonding in these compounds which was expected to stabilize their chiral structures even in solution phase. CPL properties of 1-R and 1-S were discussed in terms of transition nature of lanthanide luminescence. PMID- 22667354 TI - Dimerization of the transmembrane domain of human tetherin in membrane mimetic environments. AB - Tetherin/Bst-2 is a cell surface protein that can act as a restriction factor against a number of enveloped viruses, including HIV-1. It acts by tethering new virus particles to the host cell membrane, promoting their internalization and degradation. Tetherin is a type II membrane protein, with an N-terminal transmembrane domain, an extracellular coiled-coil domain, and a C-terminal GPI anchor. This double membrane anchor is important for anti-HIV activity, as is dimerization of the coiled-coil domain, but despite recent crystal structures of the coiled-coil ectodomains of human and mouse tetherin, the topology of tetherin with respect to host and viral membranes has yet to be determined. The tetherin transmembrane domain is also thought to mediate interactions with the HIV-1 encoded integral membrane protein Vpu, which is an antagonist of tetherin, through direct binding to the transmembrane region of Vpu. Using a combination of SDS-PAGE, size exclusion chromatography, and pyrene excimer fluorescence, we show that in the absence of the coiled-coil domain the transmembrane domain of human tetherin forms parallel homodimers in membrane mimetic environments. Transmembrane domain dimerization does not require disulfide bond formation and is favored in TFE, SDS micelles, and POPC liposomes. This observation has implications for functional models of tetherin, suggesting that both transmembrane domains in the dimeric molecule are inserted into the same lipid bilayer, rather than into opposing membranes. PMID- 22667397 TI - Monsanto. PMID- 22667396 TI - Theoretical investigation of the He4Br2 conformers. AB - Full dimensional quantum dynamics calculations of the three lowest isomers of the He(4)Br(2) van der Waals molecule in its ground electronic state are reported. The calculations are performed using the multiconfiguration time-dependent Hartree (MCTDH) method and a realistic potential form that includes the sum of three body ab initio coupled-cluster single double triple [CCSD(T)] He-Br(2) interactions plus the He-He and Br-Br interactions. This potential exhibits several multiple minima, with the three lowest ones lying very close in energy, just within 2 cm(-1). Such small differences are also found in the calculated binding energies of the three most stable conformers, indicating the floppiness of the system and, thus, the need of accurate potential forms and quantum full dynamics methods to treat this kind of complexes. The 12 dimensional results reported in this work present benchmark data and, thus, can serve to evaluate approximate methods aiming to describe higher order rare gas-dihalogen (N > 4) complexes. A comparison with previous studies using different potential forms and approaches to the energetics for the He(4)Br(2) cluster is also presented. PMID- 22667351 TI - Relationships between the renal handling of DMPS and DMSA and the renal handling of mercury. AB - Within the body of this review, we provide updates on the mechanisms involved in the renal handling mercury (Hg) and the vicinal dithiol complexing/chelating agents, 2,3-bis(sulfanyl)propane-1-sulfonate (known formerly as 2,3 dimercaptopropane-1-sulfonate, DMPS) and meso-2,3-bis(sulfanyl)succinate (known formerly as meso-2,3-dimercaptosuccinate, DMSA), with a focus on the therapeutic effects of these dithiols following exposure to different chemical forms of Hg. We begin by reviewing briefly some of the chemical properties of Hg, with an emphasis on the high bonding affinity between mercuric ions and reduced sulfur atoms, principally those contained in protein and nonprotein thiols. A discussion is provided on the current body of knowledge pertaining to the handling of various mercuric species within the kidneys, focusing on the primary cellular targets that take up and are affected adversely by these species of Hg, namely, proximal tubular epithelial cells. Subsequently, we provide a brief update on the current knowledge on the handling of DMPS and DMSA in the kidneys. In particular, parallels are drawn between the mechanisms participating in the uptake of various thiol S-conjugates of Hg in proximal tubular cells and mechanisms by which DMPS and DMSA gain entry into these target epithelial cells. Finally, we discuss factors that permit DMPS and DMSA to bind intracellular mercuric ions and mechanisms transporting DMPS and DMSA S-conjugates of Hg out of proximal tubular epithelial cells into the luminal compartment of the nephron, and promoting urinary excretion. PMID- 22667398 TI - Reduction of nitrogen oxide emissions. PMID- 22667400 TI - The Mexican environment. PMID- 22667401 TI - Pesticide stability. PMID- 22667403 TI - Phthalates in sediments. PMID- 22667402 TI - Thermospray spectra. PMID- 22667405 TI - Mixed substrate effects. PMID- 22667404 TI - Starvation promoters. PMID- 22667407 TI - Vapor extraction. PMID- 22667406 TI - Comparative risk limits. PMID- 22667408 TI - Wetlands treatment. PMID- 22667410 TI - Removing heavy metals. PMID- 22667409 TI - Pore-water methods. PMID- 22667411 TI - Decision-analytic tests. PMID- 22667412 TI - Clean car compromise advanced by EPA. PMID- 22667414 TI - Neurotoxicity risk guidelines proposed. PMID- 22667413 TI - Cancer risk assessment guidelines delayed. PMID- 22667415 TI - Final storm water permit rule issued. PMID- 22667416 TI - Government purchasing guide to green products. PMID- 22667417 TI - Current N02 standard deemed sufficient. PMID- 22667418 TI - Authors, reviewers, and potential contributors. PMID- 22667419 TI - Now get all the product. PMID- 22667420 TI - EPA toxic use reporting plan hits strong industry opposition. PMID- 22667421 TI - Environment emerges as key issue in 1996 election. PMID- 22667422 TI - Superfund research program threatened by Congress, EPA. PMID- 22667423 TI - California evaluates smog-eating automotive coating technology. PMID- 22667424 TI - Continuous emissions monitor for heavy metals patented. PMID- 22667425 TI - States, ASTM developing standards for voluntary cleanups. PMID- 22667426 TI - Federal facility cleanup "principles" to involve communities. PMID- 22667428 TI - Greenpeace disrupts chemical industry meeting. PMID- 22667427 TI - Nations to draft treaty to phase out persistent pollutants. PMID- 22667429 TI - Utilities cut pollution, save money, but few trade allowances. PMID- 22667431 TI - Briefs. PMID- 22667430 TI - Unfunded mandate. PMID- 22667432 TI - Acme chemical company. PMID- 22667434 TI - EPA investigating cross-media emissions trading. PMID- 22667433 TI - A cross-media approach to saving the chesapeake bay. PMID- 22667436 TI - Engineering enzymes for better bioremediation. PMID- 22667435 TI - Predicting chemical risks with multimedia fate models. PMID- 22667437 TI - Cell-free enzymes: Antidotes to toxic terrorism? PMID- 22667439 TI - Classified section. PMID- 22667441 TI - Regioselective Rh(I)-catalyzed sequential hydrosilylation toward the assembly of silicon-based peptidomimetic analogues. AB - A highly regioselective Rh(I)-catalyzed hydrosilylation of enamides is presented. This mild protocol allows access to a wide variety of different arylsilanes with substitution at the beta-position of the enamide and functionalization on the alkyl chain tethered to the silane. This protocol is extended to include a sequential one-pot hydrosilylation. Using diphenylsilane as the appendage point, hydrosilylation of a protected allyl alcohol followed by hydrosilylation of an enamide generates a complex organosilane in one step. This highly convergent strategy to synthesize these functionalized systems now provides a way for the rapid assembly of a diverse collection of silane-based peptidomimetic analogues. PMID- 22667442 TI - Perylenetetracarboxylic diimide derivatives linked with spirobifluorene. AB - A series of perylenetetracarboxylic diimide (PDI) compounds linked with spirobifluorene have been prepared. The orthogonal configuration of the PDI subunits efficiently hindered their molecular aggregation in solution. Energy transfer from a 1,7-diphenoxyl group substituted PDI (PO-PDI) to a 1,7 dipyrrolidinyl group substituted PDI (PY-PDI) occurred with a large efficiency when PO-PDI was selectively excited, despite the orthogonal orientation of the two units. This observation was in direct conflict with predictions derived from the Forster theory. More interestingly, this efficient energy transfer also occurred in the solid state. PMID- 22667443 TI - Copper-catalyzed arylation of o-bromoanilides: highly flexible synthesis of hexahydropyrroloindole alkaloids. AB - In the presence of catalytic amount of copper iodide, a remote amide-assisted intramolecular arylation followed by alkylation leads to a general and flexible synthetic method toward the synthesis of medicinally interesting hexahydropyrroloindole alkaloids. PMID- 22667444 TI - Extension plant pathology: strengthening resources to continue serving the public interest. AB - Extension plant pathologists deliver science-based information that protects the economic value of agricultural and horticultural crops in the United States by educating growers and the general public about plant diseases. Extension plant pathologists diagnose plant diseases and disorders, provide advice, and conduct applied research on local and regional plant disease problems. During the last century, extension plant pathology programs have adjusted to demographic shifts in the U.S. population and to changes in program funding. Extension programs are now more collaborative and more specialized in response to a highly educated clientele. Changes in federal and state budgets and policies have also reduced funding and shifted the source of funding of extension plant pathologists from formula funds towards specialized competitive grants. These competitive grants often favor national over local and regional plant disease issues and typically require a long lead time to secure funding. These changes coupled with a reduction in personnel pose a threat to extension plant pathology programs. Increasing demand for high-quality, unbiased information and the continued reduction in local, state, and federal funds is unsustainable and, if not abated, will lead to a delay in response to emerging diseases, reduce crop yields, increase economic losses, and place U.S. agriculture at a global competitive disadvantage. In this letter, we outline four recommendations to strengthen the role and resources of extension plant pathologists as they guide our nation's food, feed, fuel, fiber, and ornamental producers into an era of increasing technological complexity and global competitiveness. PMID- 22667445 TI - Effects of cherry leaf spot on photosynthesis in tart cherry 'Montmorency' foliage. AB - Results described here span a total of three field seasons and quantitatively depict the effects of an economically important fungal pathogen (Blumeriella jaapii) on tart cherry (Prunus cerasus 'Montmorency') leaf physiology. For the first time, leaf photosynthesis, stomatal conductance (g(s)), maximum ribulose 1,5-bisphosphate carboxylation rate (V(cmax)), and maximum electron transport (J(max)) were measured as functions of visible cherry leaf spot disease (CLS) severity. Defined as the proportion of chlorotic and necrotic tissue per leaf, CLS severity was estimated from leaves of mature 'Montmorency' trees in 2007, 2008, and 2009. Briefly, as visible disease severity increased, all of the leaf level physiological parameters decreased significantly (P < 0.01) and disproportionately. Thus, the effects of visible symptoms on leaf photosynthetic metabolic function encroached upon asymptomatic tissue as well. Impairment of photosynthetic metabolism in 'Montmorency' tart cherry leaves due to CLS appears to be mediated through disproportionately large perturbations in g(s), V(cmax), and J(max). These findings offer a new perspective on the amount of damage that this serious disease can inflict. PMID- 22667446 TI - Identification of a novel locus Rmo2 conditioning resistance in barley to host specific subgroups of Magnaporthe oryzae. AB - Barley cultivars show various patterns of resistance against isolates of Magnaporthe oryzae and M. grisea. Genetic mechanisms of the resistance of five representative barley cultivars were examined using a highly susceptible barley cultivar, 'Nigrate', as a common parent of genetic crosses. The resistance of the five cultivars against Setaria, Oryza, Eleusine, and Triticum isolates of M. oryzae was all attributed to a single locus, designated as Rmo2. Nevertheless, the Rmo2 locus in each cultivar was effective against a different range of isolates. Genetic analyses of pathogenicity suggested that each cultivar carries an allele at the Rmo2 locus that recognizes a different range of avirulence genes. One allele, Rmo2.a, corresponded to PWT1, which conditioned the avirulence of Setaria and Oryza isolates on wheat, in a gene-for-gene manner. The other alleles, Rmo2.b, Rmo2.c, and Rmo2.d, corresponded to more than one avirulence gene. On the other hand, the resistance of those cultivars to another species, M. grisea, was conditioned by another locus, designated as Rmo3. These results suggest that Rmo2 is effective against a broad range of blast isolates but is specific to M. oryzae. Molecular mapping revealed that Rmo2 is located on the 7H chromosome. PMID- 22667447 TI - Identification of the rice blast resistance gene Pib in the National Small Grains Collection. AB - The Pib gene in rice confers resistance to a wide range of races of the rice blast pathogen, Magnaporthe oryzae, including race IE1k that overcomes Pita, another broad-spectrum resistance gene. In this study, the presence of Pib was determined in 164 rice germplasm accessions from a core subset of the National Small Grains Collection utilizing DNA markers and pathogenicity assays. The presence of Pib was evaluated with two simple sequence repeat (SSR) markers and a dominant marker (Pib-dom) derived from the Pib gene sequence. Pathogenicity assays using two avirulent races (IE1k and IB1) and a virulent race (IB54) were performed to verify the resistance responses of accessions. Of the 164 accessions evaluated, 109 contained the Pib gene as determined using both SSR markers and pathogenicity assays, albeit different haplotypes were detected. The remaining 52 germplasm accessions were different in their responses to the blast races IB54, IE1k, and IB1, thus indicating the presence of R gene(s) other than Pib. The accessions characterized in this study could be used for marker-assisted breeding to improve blast resistance in indica and japonica cultivars worldwide. PMID- 22667448 TI - In vivo fluorescence imaging in the second near-infrared window with long circulating carbon nanotubes capable of ultrahigh tumor uptake. AB - Cancer imaging requires selective high accumulation of contrast agents in the tumor region and correspondingly low uptake in healthy tissues. Here, by making use of a novel synthetic polymer to solubilize single-walled carbon nanotubes (SWNTs), we prepared a well-functionalized SWNT formulation with long blood circulation (half-life of ~30 h) in vivo to achieve ultrahigh accumulation of ~30% injected dose (ID)/g in 4T1 murine breast tumors in Balb/c mice. Functionalization dependent blood circulation and tumor uptake were investigated through comparisons with phospholipid-PEG solubilized SWNTs. For the first time, we performed video-rate imaging of tumors based on the intrinsic fluorescence of SWNTs in the second near-infrared (NIR-II, 1.1-1.4 MUm) window. We carried out dynamic contrast imaging through principal component analysis (PCA) to immediately pinpoint the tumor within ~20 s after injection. Imaging over time revealed increasing tumor contrast up to 72 h after injection, allowing for its unambiguous identification. The 3D reconstruction of the SWNTs distribution based on their stable photoluminescence inside the tumor revealed a high degree of colocalization of SWNTs and blood vessels, suggesting enhanced permeability and retention (EPR) effect as the main cause of high passive tumor uptake of the nanotubes. PMID- 22667449 TI - Three-dimensional real-time tracking of nanoparticles at an oil-water interface. AB - Single-particle tracking with real-time feedback control can be used to study three-dimensional nanoparticle transport dynamics. We apply the method to study the behavior of adsorbed nanoparticles at a silicone oil-water interface in a microemulsion system over a range of particles sizes from 24 nm to 2000 nm. The diffusion coefficient of large particles (>200 nm) scales inversely with particle size, while smaller particles exhibit an unexpected increase in drag force at the interface. The technique can be applied in the future to study three-dimensional dynamics in a range of systems, including complex fluids, gels, biological cells, and geological media. PMID- 22667450 TI - On pathology reports of thyroid cancer specimens: what should the clinician expect? PMID- 22667451 TI - Thyroid disorders, noncommunicable diseases that gravely impact public health: a commentary and statement by the Advisory Board of the World Thyroid Federation. PMID- 22667452 TI - Diagnostic yield of nondiagnostic thyroid nodules is not altered by timing of repeat biopsy. AB - BACKGROUND: Guidelines from the National Cancer Institute Thyroid Fine Needle Aspiration State of the Science Conference recommend a repeat fine-needle aspiration biopsy (FNAB) after 3 months for thyroid nodules with a nondiagnostic (ND) result. Our aims were to assess which factors influenced their clinical management and to determine if the timing of the repeat FNAB affects the diagnostic yield. METHODS: A retrospective institutional review of 298 patients from 1/2006 to 12/2007 with an ND FNAB was performed. The factors influencing the next step in management, including age, gender, history of radiation, presence of Hashimoto's thyroiditis, thyroid-stimulating hormone levels, and ultrasound characteristics, were evaluated. The effect of the time of the repeat FNABs on their diagnostic yield was assessed. RESULTS: Of the 298 patients in our cohort, 9% were referred directly for surgery, 76% had a repeat FNAB, and 15% were observed. Tumor size was the only independent variable correlated with treatment strategy after a ND FNAB. There was not a significant difference in diagnostic yields between repeat FNABs performed earlier than 3 months compared to those preformed later (p=0.58). CONCLUSION: The timing of repeat FNAB for an initial ND FNAB does not affect diagnostic yield of the repeat FNAB. PMID- 22667455 TI - Extended spectrum beta-lactamases, carbapenemases and mobile genetic elements responsible for antibiotics resistance in Gram-negative bacteria. AB - Infectious diseases due to Gram-negative bacteria are a leading cause of morbidity and mortality worldwide. Antimicrobial agents represent one major therapeutic tools implicated to treat these infections. The misuse of antimicrobial agents has resulted in the emergence of resistant strains of Gram negatives in particular Enterobacteriaceae and non-fermenters; they have an effect not only on a human but on the public health when bacteria use the resistance mechanisms to spread in the hospital environment and to the community outside the hospitals by means of mobile genetic elements. Gram-negative bacteria have become increasingly resistant to antimicrobial agents. They have developed several mechanisms by which they can withstand to antimicrobials, these mechanisms include the production of Extended-spectrum beta-lactamases (ESBLs) and carbapenemases, furthermore, Gram-negative bacteria are now capable of spreading such resistance between members of the family Enterobacteriaceae and non-fermenters using mobile genetic elements as vehicles for such resistance mechanisms rendering antibiotics useless. Therefore, addressing the issue of mechanisms of antimicrobial resistance is considered one of most urgent priorities. This review will help to illustrate different resistance mechanisms; ESBLs, carbapenemases encoded by genes carried by mobile genetic elements, which are used by Gram-negative bacteria to escape antimicrobial effect. PMID- 22667453 TI - Potential contribution of translational factors to triiodo-L-thyronine-induced insulin synthesis by pancreatic beta cells. AB - BACKGROUND: Thyroid hormones (THs) are known to regulate protein synthesis by acting at the transcriptional level and inducing the expression of many genes. However, little is known about their role in protein expression at the post transcriptional level, even though studies have shown enhancement of protein synthesis associated with mTOR/p70S6K activation after triiodo-L-thyronine (T3) administration. On the other hand, the effects of TH on translation initiation and polypeptidic chain elongation factors, being essential for activating protein synthesis, have been poorly explored. Therefore, considering that preliminary studies from our laboratory have demonstrated an increase in insulin content in INS-1E cells in response to T3 treatment, the aim of the present study was to investigate if proteins of translational nature might be involved in this effect. METHODS: INS-1E cells were maintained in the presence or absence of T3 (10(-6) or 10(-8) M) for 12 hours. Thereafter, insulin concentration in the culture medium was determined by radioimmunoassay, and the cells were processed for Western blot detection of insulin, eukaryotic initiation factor 2 (eIF2), p-eIF2, eIF5A, EF1A, eIF4E binding protein (4E-BP), p-4E-BP, p70S6K, and p-p70S6K. RESULTS: It was found that, in parallel with increased insulin generation, T3 induced p70S6K phosphorylation and the expression of the translational factors eIF2, eIF5A, and eukaryotic elongation factor 1 alpha (eEF1A). In contrast, total and phosphorylated 4E-BP, as well as total p70S6K and p-eIF2 content, remained unchanged after T3 treatment. CONCLUSIONS: Considering that (i) p70S6K induces S6 phosphorylation of the 40S ribosomal subunit, an essential condition for protein synthesis; (ii) eIF2 is essential for the initiation of messenger RNA translation process; and (iii) eIF5A and eEF1A play a central role in the elongation of the polypeptidic chain during the transcripts decoding, the data presented here lead us to suppose that a part of T3-induced insulin expression in INS-1E cells depends on the protein synthesis activation at the post-transcriptional level, as these proteins of the translational machinery were shown to be regulated by T3. PMID- 22667456 TI - TRP channels as therapeutic targets in airway disorders: a patent review. AB - INTRODUCTION: Chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease, affect millions of patients worldwide. New therapeutic approaches to these conditions are urgently needed since current treatment options provide only symptomatic relief. Transient receptor potential (TRP) ion channels are emerging molecular target candidates for the development of novel, disease-modifying drugs addressing airway diseases. AREAS COVERED: The authors review the patent literature on novel molecules targeting TRP channels (in particular TRPA1, TRPV1, TRPM8 and TRPC6) that are currently studied in clinical trials or are candidates for future clinical evaluation in the management of respiratory diseases. EXPERT OPINION: The patent literature highlights TRPA1 and TRPV1 channels as the most advanced therapeutic targets in respiratory disorders. TRPV1 antagonists relieve cough in preclinical studies. TRPA1 antagonists not only are anti-tussive but also show efficacy in allergic asthma models. However, to date, only minimal clinical data are available regarding the effects of selective, small-molecule TRPV1 and TRPA1 blockers in respiratory disorders. Clearly, long-term clinical studies are required to confirm the expectations based on preclinical data. In conclusion, the current status of this rapidly expanding research area raises cautious optimism for TRPA1 (and possibly also TRPV1) antagonists as promising anti-tussive/anti-asthma drug candidates. PMID- 22667457 TI - Electrophysiological monitoring of hearing function during cochlear perilymphatic perfusions. AB - CONCLUSION: The cochlear perilymphatic perfusion produces, by itself, significant effects in the cochlear physiology that could be associated with the surgical procedure. These effects need to be well characterized to allow a reliable quantification of the effects of the experimental agent being tested. OBJECTIVES: The study focused on the accurate description of the electrophysiological effects on the cochlear potential recordings of perilymphatic perfusions. METHODS: Two successive cochlear perilymphatic perfusions were carried out. The first used artificial perilymph. The second used artificial perilymph alone or a kainic acid (KA) solution in artificial perilymph. The compound action potential of the auditory nerve (CAP-AN) was recorded: (1) before the first perfusion, (2) after the first perfusion and (3) after the second perfusion, and compared between groups. RESULTS: The first intracochlear perfusion with artificial perilymph produced significant effects in the CAP-AN that could be related to the surgical procedure. These effects were analysed separately from the effects produced by the KA. In particular, the KA administered intracochlearly produced a significant increase in the latency and a decrease in the amplitude of the CAP-AN N1 wave compared with the controls that were perfused twice with artificial perilymph. PMID- 22667458 TI - Value-of-information analysis to reduce decision uncertainty associated with the choice of thromboprophylaxis after total hip replacement in the Irish healthcare setting. AB - BACKGROUND: The National Centre for Pharmacoeconomics, in collaboration with the Health Services Executive, considers the cost effectiveness of all new medicines introduced into Ireland. Health Technology Assessments (HTAs) are conducted in accordance with the existing agreed Irish HTA guidelines. These guidelines do not specify a formal analysis of value of information (VOI). OBJECTIVE: The aim of this study was to demonstrate the benefits of using VOI analysis in decreasing decision uncertainty and to examine the viability of applying these techniques as part of the formal HTA process for reimbursement purposes within the Irish healthcare system. METHOD: The evaluation was conducted from the Irish health payer perspective. A lifetime model evaluated the cost effectiveness of rivaroxaban, dabigatran etexilate and enoxaparin sodium for the prophylaxis of venous thromboembolism after total hip replacement. The expected value of perfect information (EVPI) was determined directly from the probabilistic analysis (PSA). Population-level EVPI (PEVPI) was determined by scaling up the EVPI according to the decision incidence. The expected value of perfect parameter information (EVPPI) was calculated for the three model parameter subsets: probabilities, preference weights and direct medical costs. RESULTS: In the base-case analysis, rivaroxaban dominated both dabigatran etexilate and enoxaparin sodium. PSA indicated that rivaroxaban had the highest probability of being the most cost effective strategy over a threshold range of &U20AC;0-&U20AC;100 000 per QALY. At a threshold of &U20AC;45 000 per QALY, the probability that rivaroxaban was the most cost-effective strategy was 67%. At a threshold of &U20AC;45 000 per QALY, assuming a 10-year decision time horizon, the PEVPI was &U20AC;11.96 million and the direct medical costs subset had the highest EVPPI value (&U20AC;9.00 million at a population level). In order to decrease uncertainty, a more detailed costing study was undertaken. In the subsequent analysis, rivaroxaban continued to dominate both comparators. In the PSA, rivaroxaban continued to have the highest probability of being optimal over the threshold range &U20AC;0-&U20AC;100 000 per QALY. At &U20AC;45 000 per QALY, the probability that rivaroxaban was the most cost-effective strategy increased to 80%. At &U20AC;45 000 per QALY, the 10-year PEVPI decreased to &U20AC;3.58 million and the population value associated with the direct medical costs fell to &U20AC;1.72 million. CONCLUSION: This increase in probability of cost effectiveness, coupled with a substantially reduced potential opportunity loss could influence a decision maker's confidence in making a reimbursement decision. On discussions with the decision maker we now intend to incorporate the use of VOI into our HTA process. PMID- 22667459 TI - Postinflammatory hyperpigmentation secondary to external insult: an overview of the quantitative analysis of pigmentation. AB - CONTEXT: Despite new technologies, few studies have quantified changes in melanocyte numbers associated with postinflammatory hyperpigmentation (PIH) secondary to exogenous causes. OBJECTIVE: This article aims to review what is known about the pathogenesis of PIH secondary to external insults and its relationship to the resultant degree of quantitative changes in melanocytes. METHODS: We performed a review of articles exploring PIH resulting from external cutaneous insults retrieved through database searching. We reviewed relevant articles for the pathogenesis, histopathology, and quantitative changes in melanocytes related to specific etiologies of PIH. Methodologies to quantify pigmentation changes in dermatologic conditions with clinical hyperpigmentation were also explored. RESULTS: Significant increases in melanocyte counts of irritant affected skin is seen compared with melanocyte counts of unaffected skin. An increase in melanocyte counts was also found for spontaneous inflammatory dermatoses, even in the absence of clinical hyperpigmentation. Furthermore, changes in melanocyte density and appearance are also seen secondary to inflammation. In addition, increases in epidermal melanocytes are seen with cutaneous exposure to certain agents, and melanocyte increases vary by exposure agent. CONCLUSIONS: The degree of hyperpigmentation related to the intensity and duration of exposure to the causative factors of PIH is essential to better understand the pathophysiology of the disease process. The application of new methodologies to determine quantitative changes in melanocytes elicited by specific causative inflammatory agents has implications to prevent PIH, add to knowledge about disease duration, to develop better treatments for PIH, and to aid our understanding of the biology of the melanocyte. PMID- 22667461 TI - Factors associated with drug-related psychiatric disorders and suicide attempts among illicit drug users in Taiwan. AB - Illicit drug users, entering a detention center and two psychiatric hospitals in Northern Taiwan, were interviewed for lifetime drug-use-related psychiatric disorders and suicide attempts. Among 197 participants, 17.3%, 16.8%, and 14.2% had a drug-induced psychotic disorder (DIP), a drug-induced mood disorder (DIM), and a history of suicide attempts, respectively. Continuous use of methamphetamine and joblessness were associated with DIP and DIM, accordingly. Polysubstance use was collectively correlated with DIP and DIM. Female gender and history of having any mood disorder were predictors of suicide. These results provide useful clues for detecting drug-related psychiatric disorders and suicide among illicit drug users. The study's limitations are noted. PMID- 22667460 TI - Protein kinase C-mediated regulation of matrix metalloproteinase and tissue inhibitor of metalloproteinase production in a human retinal muller cells. AB - PURPOSE: Matrix metalloproteinases (MMPs) play an important role in the degradation of extracellular matrix (ECM) proteins in the retina. Breakdown of ECM proteins results in neovascularization and tractional retinal detachment, which eventually lead to the symptoms of proliferative diabetic retinopathy. Muller cells are reported to be one of the MMP-producing cells in the retina. However, the molecular mechanism of MMP production derived from Muller cells remains to be fully elucidated. MATERIALS AND METHODS: The human retinal Muller cell line (MIO-M1) was continuously-subcultured in high glucose (25 mM) condition. After the cells reached confluence, they were treated for 24 h with phorbol ester and/or a protein kinase C (PKC) inhibitor, GF109203X in high (25 mM) or low (5 mM) glucose condition. Gelatinase activities in conditioned medium were assessed using gelatin zymography. RT-PCR was performed to analyze the mRNA expression level of MMP-9. Western blot analysis used to detect the protein expression of tissue inhibitors of metalloproteinases (TIMPs). Electrophoresis mobility shift assay was conducted to examine transcription factors involved in MMP-9 transcription. RESULTS: We demonstrated the protein kinase C (PKC)-mediated regulation of proMMP-9 transcription and protein expression through the action of phorbol ester, an activator of PKC. Moreover, we demonstrated the expression of TIMPs, known as natural inhibitors of MMPs at the protein level in a human retinal Muller cell line for the first time, and report that production of these proteins was also regulated in a PKC-dependent manner. CONCLUSION: Our results suggest that imbalance between MMP and TIMP proteins may promote neovascularization by PKC activation in retinal Muller cells. In addition, the development of novel compounds with regulatory action on MMP and TIMP production through inhibiting PKC activity in retinal Muller cells may lead to new therapeutic approaches for the treatment and prevention of diabetic retinopathy. PMID- 22667462 TI - The role of periostin in eosinophilic otitis media. AB - CONCLUSION: We investigated the localization of periostin in middle ear specimens from patients with eosinophilic otitis media (EOM) and from a newly constructed animal model for EOM. Periostin-positive immunostaining was observed in the middle ear sections obtained from the EOM patients. Immunoreactivity for periostin was also seen in the animal model. These results suggest that periostin plays an important role in subepithelial fibrosis in the middle ear in EOM. OBJECTIVE: The purpose of the present study was to investigate the role of periostin in the middle ear of EOM patients and an animal model. METHODS: Histological and immunohistochemical analyses for periostin were carried out in the middle ear specimens of six EOM patients with/without asthma. An animal model of EOM was constructed by intraperitoneal and topical sensitization with ovalbumin (OVA). Histological and immunocytochemical analyses for periostin were also performed in this model. RESULTS: Immunoreactivities for periostin were observed in the basement membrane and extracellular matrix of the middle ear sections obtained from all EOM patients with/without asthma. In the animal model, eosinophil infiltration and middle ear mucosa thickness were observed. Moreover, periostin-positive immunostaining was shown in the extracellular matrix of the middle ear mucosa on the side topically boosted by OVA. PMID- 22667465 TI - A new and reliable animal model for optic nerve injury. AB - OBJECTIVE: To create an animal (rat) model of force percussion injury (FPI) to the optic nerve for clinical and experimental research. METHODS: Seventy-one healthy female Wister rats, with no ocular disorders, were used in this study. Sixty-six rats were subjected to bilateral blunt trauma to the eyes via FPI; five rats were not subjected to trauma. According to the degree of optic nerve injury, injured eyes were divided into two groups: severe optic nerve injury group, with beat pressures of 699.14 +/- 60.79 kPa and mild optic nerve injury group, with beat pressures of 243.18 +/- 20.26 kPa. Eight rats were examined using flash visual-evoked potential (F-VEP) monitoring and magnetic resonance imaging (MRI) before, 1 and 3 days, and 1, 2, 4, 6, and 8 weeks after optic nerve injury. Fifty six rats were examined by histopathology and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay for apoptosis at 1 and 3 days, and 1, 2, 4, 6, and 8 weeks after optic nerve injury. Two rats were examined by transmission electron microscopy (TEM) 4 and 8 weeks after optic nerve injury. The presence or absence of optic nerve injury was evaluated in all trauma eyes. RESULTS: Latency was prolonged in the severe injury group compared with controls 1 day after optic nerve injury (p < .05). Amplitude decreased during the first 2 weeks after optic nerve injury (p < .05) and then stabilized (p > .05). Latency was prolonged in the mild optic nerve injury group compared with controls 1 day after optic nerve injury (p < .05) Amplitude decreased during the first 4 weeks (p < .05) following injury and then stabilized (p > .05). As measured by MRI, an abnormally high signal was seen 1 day after injury and remained significantly high 8 weeks after injury. A ruptured capillary was detected in the ganglion cell layer (GCL) 1 day after injury. Acellular regions in the ganglion cell layer were observed 4 weeks after optic nerve injury. TUNEL positive cells were present in each layer of the retina 3 days after injury. The number of TUNEL-positive cells began to increase 1-2 weeks after injury, and then gradually decreased 4 weeks after injury (p < .05). CONCLUSION: We successfully created a reproducible experimental animal (rat) model of optic nerve injury using FPI. Optic nerve injury was demonstrated by F-VEP and MRI, and confirmed histologically. Our model is a simple, reliable, reproducible, and stable tool for use in investigations on the mechanism(s) of and treatment for optic nerve injury. PMID- 22667466 TI - High-frequency hearing impairment assessed with cochlear microphonics. AB - CONCLUSION: Cochlear microphonic (CM) measurements may potentially become a supplementary approach to otoacoustic emission (OAE) measurements for assessing low-frequency cochlear functions in the clinic. OBJECTIVE: The objective of this study was to investigate the measurement of CMs in subjects with high-frequency hearing loss. Currently, CMs can be measured using electrocochleography (ECochG or ECoG) techniques. Both CMs and OAEs are cochlear responses, while auditory brainstem responses (ABRs) are not. However, there are inherent limitations associated with OAE measurements such as acoustic noise, which can conceal low frequency OAEs measured in the clinic. However, CM measurements may not have these limitations. METHODS: CMs were measured in human subjects using an ear canal electrode. The CMs were compared between the high-frequency hearing loss group and the normal-hearing control group. Distortion product OAEs (DPOAEs) and audiogram were also measured. RESULTS: The DPOAE and audiogram measurements indicate that the subjects were correctly selected for the two groups. Low frequency CM waveforms (CMWs) can be measured using ear canal electrodes in high frequency hearing loss subjects. The difference in amplitudes of CMWs between the high-frequency hearing loss group and the normal-hearing group is insignificant at low frequencies but significant at high frequencies. PMID- 22667464 TI - Covalent modification of lipids and proteins in rat hepatocytes and in vitro by thioacetamide metabolites. AB - Thioacetamide (TA) is a well-known hepatotoxin in rats. Acute doses cause centrilobular necrosis and hyperbilirubinemia while chronic administration leads to biliary hyperplasia and cholangiocarcinoma. Its acute toxicity requires its oxidation to a stable S-oxide (TASO) that is oxidized further to a highly reactive S,S-dioxide (TASO(2)). To explore possible parallels among the metabolism, covalent binding, and toxicity of TA and thiobenzamide (TB), we exposed freshly isolated rat hepatocytes to [(14)C]-TASO or [(13)C(2)D(3)]-TASO. TLC analysis of the cellular lipids showed a single major spot of radioactivity that mass spectral analysis showed to consist of N-acetimidoyl PE lipids having the same side chain composition as the PE fraction from untreated cells; no carbons or hydrogens from TASO were incorporated into the fatty acyl chains. Many cellular proteins contained N-acetyl- or N-acetimidoyl lysine residues in a 3:1 ratio (details to be reported separately). We also oxidized TASO with hydrogen peroxide in the presence of dipalmitoyl phosphatidylenthanolamine (DPPE) or lysozyme. Lysozyme was covalently modified at five of its six lysine side chains; only acetamide-type adducts were formed. DPPE in liposomes also gave only amide type adducts, even when the reaction was carried out in tetrahydrofuran with only 10% water added. The exclusive formation of N-acetimidoyl PE in hepatocytes means that the concentration or activity of water must be extremely low in the region where TASO(2) is formed, whereas at least some of the TASO(2) can hydrolyze to acetylsulfinic acid before it reacts with cellular proteins. The requirement for two sequential oxidations to produce a reactive metabolite is unusual, but it is even more unusual that a reactive metabolite would react with water to form a new compound that retains a high degree of chemical reactivity toward biological nucleophiles. The possible contribution of lipid modification to the hepatotoxicity of TA/TASO remains to be determined. PMID- 22667533 TI - Communication: phase transitions, criticality, and three-phase coexistence in constrained cell models. AB - In simulation studies of fluid-solid transitions, the solid phase is usually modeled as a constrained system in which each particle is confined to move in a single Wigner-Seitz cell. The constrained cell model has been used in the determination of fluid-solid coexistence via thermodynamic integration and other techniques. In the present work, the phase diagram of such a constrained system of Lennard-Jones particles is determined from constant-pressure simulations. The pressure-density isotherms exhibit inflection points which are interpreted as the mechanical stability limit of the solid phase. The phase diagram of the constrained system contains a critical and a triple point. The temperature and pressure at the critical and the triple point are both higher than those of the unconstrained system due to the reduction in the entropy caused by the single occupancy constraint. PMID- 22667467 TI - Pulsed ENDOR determination of the arginine location in the ferrous-NO form of neuronal NOS. AB - Mammalian nitric oxide synthases (NOSs) are enzymes responsible for oxidation of L-arginine (L-Arg) to nitric oxide (NO). Mechanisms of reactions at the catalytic heme site are not well understood, and it is of current interest to study structures of the heme species that activates O(2) and transforms the substrate. The NOS ferrous-NO complex is a close mimic of the obligatory ferric (hydro)peroxo intermediate in NOS catalysis. In this work, pulsed electron nuclear double resonance (ENDOR) was used to probe the position of the l-Arg substrate at the NO(*)-coordinated ferrous heme center(s) in the oxygenase domain of rat neuronal NOS (nNOS). The analysis of (2)H and (15)N ENDOR spectra of samples containing d(7)- or guanidino-(15)N(2) labeled L-Arg has resulted in distance estimates for the nearby guanidino nitrogen and the nearby proton (deuteron) at C(delta). The L-Arg position was found to be noticeably different from that in the X-ray crystal structure of nNOS ferrous-NO complex [Li et al. J. Biol. Inorg. Chem.2006, 11, 753-768], with the nearby guanidino nitrogen being ~0.5 A closer to, and the nearby H(delta) about 1 A further from, the NO ligand than in the X-ray structure. The difference might be related to the structural constraints imposed on the protein by the crystal. Importantly, in spite of its closer position, the guanidino nitrogen does not form a hydrogen bond with the NO ligand, as evidenced by the absence of significant isotropic hfi constant for N(g1). This is consistent with the previous reports that it is not the L-Arg substrate itself that would most likely serve as a direct proton donor to the diatomic ligands (NO and O(2)) bound to the heme. PMID- 22667534 TI - Many-body calculations of low-energy eigenstates in magnetic and periodic systems with self-healing diffusion Monte Carlo: steps beyond the fixed phase. AB - The self-healing diffusion Monte Carlo algorithm (SHDMC) [F. A. Reboredo, R. Q. Hood, and P. R. C. Kent, Phys. Rev. B 79, 195117 (2009); F. A. Reboredo, ibid. 80, 125110 (2009)] is extended to study the ground and excited states of magnetic and periodic systems. The method converges to exact eigenstates as the statistical data collected increase if the wave function is sufficiently flexible. It is shown that the dimensionality of the nodal surface is dependent on whether phase is a scalar function or not. A recursive optimization algorithm is derived from the time evolution of the mixed probability density, which is given by an ensemble of electronic configurations (walkers) with complex weight. This complex weight allows the phase of the fixed-node wave function to move away from the trial wave function phase. This novel approach is both a generalization of SHDMC and the fixed-phase approximation [G. Ortiz, D. M. Ceperley, and R. M. Martin, Phys Rev. Lett. 71, 2777 (1993)]. When used recursively it simultaneously improves the node and the phase. The algorithm is demonstrated to converge to nearly exact solutions of model systems with periodic boundary conditions or applied magnetic fields. The computational cost is proportional to the number of independent degrees of freedom of the phase. The method is applied to obtain low energy excitations of Hamiltonians with magnetic field. Periodic boundary conditions are also considered optimizing wave functions with twisted boundary conditions which are included in a many-body Bloch phase. The potential applications of this new method to study periodic, magnetic, and complex Hamiltonians are discussed. PMID- 22667535 TI - Phase diagram and universality of the Lennard-Jones gas-liquid system. AB - The gas-liquid phase transition of the three-dimensional Lennard-Jones particles system is studied by molecular dynamics simulations. The gas and liquid densities in the coexisting state are determined with high accuracy. The critical point is determined by the block density analysis of the Binder parameter with the aid of the law of rectilinear diameter. From the critical behavior of the gas-liquid coexisting density, the critical exponent of the order parameter is estimated to be beta = 0.3285(7). Surface tension is estimated from interface broadening behavior due to capillary waves. From the critical behavior of the surface tension, the critical exponent of the correlation length is estimated to be nu = 0.63(4). The obtained values of beta and nu are consistent with those of the Ising universality class. PMID- 22667536 TI - General formulation of spin-flip time-dependent density functional theory using non-collinear kernels: theory, implementation, and benchmarks. AB - We report an implementation of the spin-flip (SF) variant of time-dependent density functional theory (TD-DFT) within the Tamm-Dancoff approximation and non collinear (NC) formalism for local, generalized gradient approximation, hybrid, and range-separated functionals. The performance of different functionals is evaluated by extensive benchmark calculations of energy gaps in a variety of diradicals and open-shell atoms. The benchmark set consists of 41 energy gaps. A consistently good performance is observed for the Perdew-Burke-Ernzerhof (PBE) family, in particular PBE0 and PBE50, which yield mean average deviations of 0.126 and 0.090 eV, respectively. In most cases, the performance of original (collinear) SF-TDDFT with 50-50 functional is also satisfactory (as compared to non-collinear variants), except for the same-center diradicals where both collinear and non-collinear SF variants that use LYP or B97 exhibit large errors. The accuracy of NC-SF-TDDFT and collinear SF-TDDFT with 50-50 and BHHLYP is very similar. Using PBE50 within collinear formalism does not improve the accuracy. PMID- 22667537 TI - Sensitivity of the properties of ruthenium "blue dimer" to method, basis set, and continuum model. AB - The ruthenium "blue dimer" [(bpy)(2)Ru(III)OH(2)](2)O(4+) is best known as the first well-defined molecular catalyst for water oxidation. It has been subject to numerous computational studies primarily employing density functional theory. However, those studies have been limited in the functionals, basis sets, and continuum models employed. The controversy in the calculated electronic structure and the reaction energetics of this catalyst highlights the necessity of benchmark calculations that explore the role of density functionals, basis sets, and continuum models upon the essential features of blue-dimer reactivity. In this paper, we report Kohn-Sham complete basis set (KS-CBS) limit extrapolations of the electronic structure of "blue dimer" using GGA (BPW91 and BP86), hybrid GGA (B3LYP), and meta-GGA (M06-L) density functionals. The dependence of solvation free energy corrections on the different cavity types (UFF, UA0, UAHF, UAKS, Bondi, and Pauling) within polarizable and conductor-like polarizable continuum model has also been investigated. The most common basis sets of double zeta quality are shown to yield results close to the KS-CBS limit; however, large variations are observed in the reaction energetics as a function of density functional and continuum cavity model employed. PMID- 22667538 TI - Local explicitly correlated second- and third-order Moller-Plesset perturbation theory with pair natural orbitals. AB - We present an algorithm for computing explicitly correlated second- and third order Moller-Plesset energies near the basis set limit for large molecules with a cost that scales formally as N(4) with system size N. This is achieved through a hybrid approach where locality is exploited first through orbital specific virtuals (OSVs) and subsequently through pair natural orbitals (PNOs) and integrals are approximated using density fitting. Our method combines the low orbital transformation costs of the OSVs with the compactness of the PNO representation of the doubles amplitude vector. The N(4) scaling does not rely upon the a priori definition of domains, enforced truncation of pair lists, or even screening and the energies converge smoothly to the canonical values with decreasing occupation number thresholds, used in the selection of the PNO basis. For MP2.5 intermolecular interaction energies, we find that 99% of benchmark basis set limit correlation energy contributions are recovered using an aug-cc pVTZ basis and that on average only 50 PNOs are required to correlate the significant orbital pairs. PMID- 22667539 TI - Diffusion in the presence of cylindrical obstacles arranged in a square lattice analyzed with generalized Fick-Jacobs equation. AB - The generalized Fick-Jacobs equation is widely used to study diffusion of Brownian particles in three-dimensional tubes and quasi-two-dimensional channels of varying constraint geometry. We show how this equation can be applied to study the slowdown of unconstrained diffusion in the presence of obstacles. Specifically, we study diffusion of a point Brownian particle in the presence of identical cylindrical obstacles arranged in a square lattice. The focus is on the effective diffusion coefficient of the particle in the plane perpendicular to the cylinder axes, as a function of the cylinder radii. As radii vary from zero to one half of the lattice period, the effective diffusion coefficient decreases from its value in the obstacle free space to zero. Using different versions of the generalized Fick-Jacobs equation, we derive simple approximate formulas, which give the effective diffusion coefficient as a function of the cylinder radii, and compare their predictions with the values of the effective diffusion coefficient obtained from Brownian dynamics simulations. We find that both Reguera-Rubi and Kalinay-Percus versions of the generalized Fick-Jacobs equation lead to quite accurate predictions of the effective diffusion coefficient (with maximum relative errors below 4% and 7%, respectively) over the entire range of the cylinder radii from zero to one half of the lattice period. PMID- 22667540 TI - Perturbative treatment of triple excitations in internally contracted multireference coupled cluster theory. AB - Internally contracted multireference coupled cluster (ic-MRCC) methods with perturbative treatment of triple excitations are formulated based on Dyall's definition of a zeroth-order Hamiltonian. The iterative models ic-MRCCSDT-1, ic MRCC3, and their variants ic-MRCCSD(T), ic-MRCC(3) which determine the energy correction from triples by a non-iterative step are consistent in the single reference limit with CCSDT-1a, CC3, CCSD(T), and CC(3), respectively. Numerical tests on the potential energy surfaces of BeH(2), H(2)O, and N(2) as well as on the structure and harmonic vibrational frequencies of the ozone molecule show that these methods account very well for higher order correlation effects. The ic MRCCSD(T) method is further applied to the geometry optimization and harmonic frequencies of the symmetric vibrational modes of the binuclear transition metal oxide Ni(2)O(2), to the singlet-triplet splittings of o-, m-, and p-benzyne and to a ring-opening reaction of an azirine compound with the molecular formula C(6)H(7)NO. The size of the active spaces used in this study ranges from CAS(2,2) to CAS(8,8). Comparisons of results based on differently sized active spaces indicate that the ic-MRCCSD(T) method provides a highly accurate and efficient treatment of both static and dynamic electron correlation in connection with minimal active spaces. PMID- 22667541 TI - A sequential transformation approach to the internally contracted multireference coupled cluster method. AB - The internally contracted multireference coupled cluster (ic-MRCC) approach is formulated using a new wave function ansatz based on a sequential transformation of the reference function (sqic-MRCC). This alternative wave function simplifies the formulation of computationally viable methods while preserving the accuracy of the ic-MRCC approach. The structure of the sqic-MRCC wave function allows folding the effect of the single excitations into a similarity-transformed Hamiltonian whose particle rank is equal to the one of the Hamiltonian. Consequently, we formulate an approximation to the sqic-MRCC method with singles and doubles (included respectively up to fourfold and twofold commutators, sqic MRCCSD[2]) that contains all terms present in the corresponding single-reference coupled cluster scheme. Computations of the potential energy curves for the dissociation of BeH(2) show that the untruncated sqic-MRCCSD scheme yields results that are almost indistinguishable from the ordinary ic-MRCCSD method. The energy obtained from the computationally less expensive sqic-MRCCSD[2] approximation is found to deviate from the full ic-MRCCSD method by less than 0.2 mE(h) for BeH(2), while, in the case of water, the harmonic vibrational frequencies of ozone, the singlet-triplet splitting of p-benzyne, and the dissociation curve of N(2), sqic-MRCCSD[2] faithfully reproduces the results obtained via the ic-MRCCSD scheme truncated to two commutators. A formal proof is given of the equivalence of the ic-MRCC and sqic-MRCC methods with the internally contracted and full configuration interaction approaches. PMID- 22667542 TI - Dispersion-free component of non-covalent interaction via mutual polarization of fragment densities. AB - Comprehensive tests within a diverse set of noncovalently bonded systems are carried out to assess the performance of the recently-developed dispersion-free approach in the framework of density functional theory [L. Rajchel, P. Zuchowski, M. Szczesniak, and G. Chalasinski, Phys. Rev. Lett. 104, 163001 (2010)]. A numerical algorithm which cures the convergence problems of the previous implementation is presented. PMID- 22667543 TI - Explicitly correlated second-order Moller-Plesset perturbation theory employing pseudospectral numerical quadratures. AB - We implemented explicitly correlated second-order Moller-Plesset perturbation theory with numerical quadratures using pseudospectral construction of grids. Introduction of pseudospectral approach for the calculation of many-electron integrals gives a possibility to use coarse grids without significant loss of precision in correlation energies, while the number of points in the grid is reduced about nine times. The use of complementary auxiliary basis sets as the sets of dealiasing functions is justified at both theoretical and computational levels. Benchmark calculations for a set of 16 molecules have shown the possibility to keep an error of second-order correlation energies within 1 milihartree (mH) with respect to MP2-F12 method with dense grids. Numerical tests for a set of 13 isogyric reactions are also performed. PMID- 22667544 TI - Derivative discontinuity, bandgap and lowest unoccupied molecular orbital in density functional theory. AB - The conventional analysis of Perdew and Levy, and Sham and Schluter shows that the functional derivative discontinuity of the exchange-correlation density functional plays a critical role in the correct prediction of bandgaps, or the chemical hardness. In a recent work by the present authors, explicit expressions for bandgap prediction with all common types of exchange-correlation functionals have been derived without invoking the concept of exchange-correlation energy functional derivative discontinuity at all. We here analyze the two approaches and establish their connection and difference. The present analysis further leads to several important results: (1) The lowest unoccupied molecular orbital (LUMO) in DFT has as much meaning in describing electron addition as the highest occupied molecular orbital (HOMO) in describing electron removal. (2) Every term in the total energy functional contributes to the energy gap because of the discontinuity of the derivative of the density (or density matrix) with respect to the number of electrons, ((?rho(s)(r('),r))/?N)(v(s) ), at integers. (3) Consistent with the Perdew-Levy-Sham-Schluter conclusion that the exact Kohn-Sham energy gap differs from the fundamental bandgap by a finite correction due to the functional derivative discontinuity of the exchange-correlation energy, we show that the exchange-correlation functional cannot be an explicit and differentiable functional of the electron density, either local or nonlocal. The last result is further strengthened when we consider Mott insulators. There, the exact exchange correlation functional needs to have an explicitly discontinuous (nondifferentiable) dependence on the density or the density matrix. (4) We obtain exact conditions on the derivatives of total energy with respect to the spin-up and spin-down number of electrons. PMID- 22667545 TI - Analytic gradient for second order Moller-Plesset perturbation theory with the polarizable continuum model based on the fragment molecular orbital method. AB - A new energy expression is proposed for the fragment molecular orbital method interfaced with the polarizable continuum model (FMO/PCM). The solvation free energy is shown to be more accurate on a set of representative polypeptides with neutral and charged residues, in comparison to the original formulation at the same level of the many-body expansion of the electrostatic potential determining the apparent surface charges. The analytic first derivative of the energy with respect to nuclear coordinates is formulated at the second-order Moller-Plesset (MP2) perturbation theory level combined with PCM, for which we derived coupled perturbed Hartree-Fock equations. The accuracy of the analytic gradient is demonstrated on test calculations in comparison to numeric gradient. Geometry optimization of the small Trp-cage protein (PDB: 1L2Y) is performed with FMO/PCM/6-31(+)G(d) at the MP2 and restricted Hartree-Fock with empirical dispersion (RHF/D). The root mean square deviations between the FMO optimized and NMR experimental structure are found to be 0.414 and 0.426 A for RHF/D and MP2, respectively. The details of the hydrogen bond network in the Trp-cage protein are revealed. PMID- 22667546 TI - Estimating statistical distributions using an integral identity. AB - We present an identity for an unbiased estimate of a general statistical distribution. The identity computes the distribution density from dividing a histogram sum over a local window by a correction factor from a mean-force integral, and the mean force can be evaluated as a configuration average. We show that the optimal window size is roughly the inverse of the local mean-force fluctuation. The new identity offers a more robust and precise estimate than a previous one by Adib and Jarzynski [J. Chem. Phys. 122, 014114 (2005)]. It also allows a straightforward generalization to an arbitrary ensemble and a joint distribution of multiple variables. Particularly we derive a mean-force enhanced version of the weighted histogram analysis method. The method can be used to improve distributions computed from molecular simulations. We illustrate the use in computing a potential energy distribution, a volume distribution in a constant pressure ensemble, a radial distribution function, and a joint distribution of amino acid backbone dihedral angles. PMID- 22667547 TI - Symmetric and asymmetric triple excitation corrections for the orbital-optimized coupled-cluster doubles method: improving upon CCSD(T) and CCSD(T)(Lambda): preliminary application. AB - Symmetric and asymmetric triple excitation corrections for the orbital-optimized coupled-cluster doubles (OO-CCD or simply "OD" for short) method are investigated. The conventional symmetric and asymmetric perturbative triples corrections [(T) and (T)(Lambda)] are implemented, the latter one for the first time. Additionally, two new triples corrections, denoted as OD(Lambda) and OD(Lambda)(T), are introduced. We applied the new methods to potential energy surfaces of the BH, HF, C(2), N(2), and CH(4) molecules, and compare the errors in total energies, with respect to full configuration interaction, with those from the standard coupled-cluster singles and doubles (CCSD), with perturbative triples [CCSD(T)], and asymmetric triples correction (CCSD(T)(Lambda)) methods. The CCSD(T) method fails badly at stretched geometries, the corresponding nonparallelity error is 7-281 kcal mol(-1), although it gives reliable results near equilibrium geometries. The new symmetric triples correction, CCSD(Lambda), noticeably improves upon CCSD(T) (by 4-14 kcal mol(-1)) for BH, HF, and CH(4); however, its performance is worse than CCSD(T) (by 1.6-4.2 kcal mol(-1)) for C(2) and N(2). The asymmetric triples corrections, CCSD(T)(Lambda) and CCSD(Lambda)(T), perform remarkably better than CCSD(T) (by 5-18 kcal mol(-1)) for the BH, HF, and CH(4) molecules, while for C(2) and N(2) their results are similar to those of CCSD(T). Although the performance of CCSD and OD is similar, the situation is significantly different in the case of triples corrections, especially at stretched geometries. The OD(T) method improves upon CCSD(T) by 1 279 kcal mol(-1). The new symmetric triples correction, OD(Lambda), enhances the OD(T) results (by 0.01-2.0 kcal mol(-1)) for BH, HF, and CH(4); however, its performance is worse than OD(T) (by 1.9-2.3 kcal mol(-1)) for C(2) and N(2). The asymmetric triples corrections, OD(T)(Lambda) and OD(Lambda)(T), perform better than OD(T) (by 2.0-6.2 kcal mol(-1)). The latter method is slightly better for the BH, HF, and CH(4) molecules. However, for C(2) and N(2) the new results are similar to those of OD(T). For the BH, HF, and CH(4) molecules, OD(Lambda)(T) provides the best potential energy curves among the considered methods, while for C(2) and N(2) the OD(T) method prevails. Hence, for single-bond breaking the OD(Lambda)(T) method appears to be superior, whereas for multiple-bond breaking the OD(T) method is better. PMID- 22667548 TI - Quantum continuum mechanics made simple. AB - In this paper we further explore and develop the quantum continuum mechanics (QCM) of Tao et al. [Phys. Rev. Lett. 103, 086401 (2009)] with the aim of making it simpler to use in practice. Our simplifications relate to the non-interacting part of the QCM equations, and primarily refer to practical implementations in which the groundstate stress tensor is approximated by its Kohn-Sham (KS) version. We use the simplified approach to directly prove the exactness of QCM for one-electron systems via an orthonormal formulation. This proof sheds light on certain physical considerations contained in the QCM theory and their implication on QCM-based approximations. The one-electron proof then motivates an approximation to the QCM (exact under certain conditions) expanded on the wavefunctions of the KS equations. Particular attention is paid to the relationships between transitions from occupied to unoccupied KS orbitals and their approximations under the QCM. We also demonstrate the simplified QCM semianalytically on an example system. PMID- 22667549 TI - First principle nonlinear quantum dynamics using a correlation-based von Neumann entropy. AB - A new concept to describe the quantum dynamics in complex systems is suggested. It extends established schemes based on the Dirac-Frenkel variation principle, e.g., the multi-configurational time-dependent Hartree (MCTDH) approach. The concept is based on a correlation-based von Neumann entropy (CvN-entropy) definition measuring the complexity of the wavefunction. Equations of motion are derived using a CvN-entropy constraint in the variational principle and result in a generally applicable effective Hamiltonian. It consists of the standard Hamilton operator and an additional nonlinear operator which limits the complexity of the wavefunction. Effectively, this nonlinear operator absorbs complex structures which are emerging in the wavefunction and allows one to introduce non-norm conserving equations of motion. Important aspects of the new concept are outlined studying the wave packet propagation on the diabatic B(2) potential energy surfaces of NO(2). First, it is demonstrated that during standard wave packet propagation the CvN-entropy increases strongly with time roughly independent of the coordinate systems employed. Second, one finds that employing CvN-entropy constrained MCTDH propagation yields improved wave function accuracy on longer time scales while compromising on the short time accuracy. Third, the loss of the wavefunction's norm is directly related to the overlap with the exact wavefunction. This provides an error estimate available without knowing an exact reference. PMID- 22667550 TI - Analysis of the Heyd-Scuseria-Ernzerhof density functional parameter space. AB - The Heyd-Scuseria-Ernzerhof (HSE) density functionals are popular for their ability to improve upon the accuracy of standard semilocal functionals such as Perdew-Burke-Ernzerhof (PBE), particularly for semiconductor band gaps. They also have a reduced computational cost compared to hybrid functionals, which results from the restriction of Fock exchange calculations to small inter-electron separations. These functionals are defined by an overall fraction of Fock exchange and a length scale for exchange screening. We systematically examine this two-parameter space to assess the performance of hybrid screened exchange (sX) functionals and to determine a balance between improving accuracy and reducing the screening length, which can further reduce computational costs. Three parameter choices emerge as useful: "sX-PBE" is an approximation to the sX LDA screened exchange density functionals based on the local density approximation (LDA); "HSE12" minimizes the overall error over all tests performed; and "HSE12s" is a range-minimized functional that matches the overall accuracy of the existing HSE06 parameterization but reduces the Fock exchange length scale by half. Analysis of the error trends over parameter space produces useful guidance for future improvement of density functionals. PMID- 22667551 TI - Approximate inclusion of four-mode couplings in vibrational coupled-cluster theory. AB - The vibrational coupled cluster (VCC) equations are analyzed in terms of vibrational Moller-Plesset perturbation theory aiming specifically at the importance of four-mode couplings. Based on this analysis, new VCC methods are derived for the calculation of anharmonic vibrational energies and vibrational spectra using vibrational coupled cluster response theory. It is shown how the effect of four-mode coupling and excitations can be efficiently and accurately described using approximations for their inclusion. Two closely related approaches are suggested. The computational scaling of the so-called VCC[3pt4F] method is not higher than the fifth power in the number of vibrational degrees of freedom when up to four-mode coupling terms are present in the Hamiltonian and only fourth order when only up to three-mode couplings are present. With a further approximation, one obtains the VCC[3pt4] model which is shown to scale with at most the fourth power in the number of vibrational degrees of freedom for Hamiltonians with both three- and four-mode coupling levels, while sharing the most important characteristics with VCC[3pt4F]. Sample calculations reported for selected tetra-atomic molecules as well as the larger dioxirane and ethylene oxide molecules support that the new models are accurate and useful. PMID- 22667552 TI - Theoretical study of the nuclear spin-molecular rotation coupling for relativistic electrons and non-relativistic nuclei. AB - A theoretical study of the relation between the relativistic formulation of the nuclear magnetic shielding and spin-rotation tensors is presented. To this end a theoretical expression of the relativistic spin-rotation tensor is formulated, considering a molecular Hamiltonian of relativistic electrons and non relativistic nuclei. Molecular rotation effects are introduced considering the terms of the Born-Oppenheimer decomposition, which couple the electrons and nuclei dynamics. The loss of the simple relation linking both spectral parameters in the non-relativistic formulation is further analyzed carrying out a perturbative expansion of relativistic effects by means of the linear response within the elimination of the small component approach. It is concluded that relativistic effects on the spin-rotation tensor are less important than those of the nuclear magnetic shielding tensor. PMID- 22667553 TI - Accuracy of second order perturbation theory in the polaron and variational polaron frames. AB - In the study of open quantum systems, the polaron transformation has recently attracted a renewed interest as it offers the possibility to explore the strong system-bath coupling regime. Despite this interest, a clear and unambiguous analysis of the regimes of validity of the polaron transformation is still lacking. Here we provide such a benchmark, comparing second order perturbation theory results in the original untransformed frame, the polaron frame, and the variational extension with numerically exact path integral calculations of the equilibrium reduced density matrix. Equilibrium quantities allow a direct comparison of the three methods without invoking any further approximations as is usually required in deriving master equations. It is found that the second order results in the original frame are accurate for weak system-bath coupling; the results deteriorate when the bath cut-off frequency decreases. The full polaron results are accurate for the entire range of coupling for a fast bath but only in the strong coupling regime for a slow bath. The variational method is capable of interpolating between these two methods and is valid over a much broader range of parameters. PMID- 22667554 TI - Complexes of type C6H7(+).L (L = N2 and CO2) studied by explicitly correlated coupled cluster theory. AB - Complexes of the benzenium ion (C(6)H(7)(+)) with N(2) or CO(2) have been studied by explicitly correlated coupled cluster theory at the CCSD(T)-F12x (x = a, b) level [T. B. Adler et al., J. Chem. Phys. 127, 221106 (2007)] and the double hybrid density functional B2PLYP-D [T. Schwabe and S. Grimme, Phys. Chem. Chem. Phys. 9, 3397 (2007)]. Improved harmonic vibrational wavenumbers for C(6)H(7)(+) have been obtained by CCSD(T*)-F12a calculations with the VTZ-F12 basis set. Combining them with previous B2PLYP-D anharmonic contributions we arrive at anharmonic wavenumbers which are in excellent agreement with recent experimental data from p-H(2) matrix isolation IR spectroscopy [M. Bahou et al., J. Chem. Phys. 136, 154304 (2012)]. The energetically most favourable conformer of C(6)H(7)(+).N(2) shows a pi-bonded structure similar to C(6)H(7)(+).Rg (Rg = Ne, Ar) [P. Botschwina and R. Oswald, J. Phys. Chem. A 115, 13664 (2011)] with D(e) ~ 870 cm(-1). For C(6)H(7)(+).CO(2), a slightly lower energy is calculated for a conformer with the CO(2) ligand lying in the ring-plane of the C(6)H(7)(+) moiety (D(e) ~ 1508 cm(-1)). It may be discriminated from other conformers through a strong band predicted at 1218 cm(-1), red-shifted by 21 cm(-1) from the corresponding band of free C(6)H(7)(+). PMID- 22667555 TI - Angular and energy distribution of fragment ions in dissociative double photoionization of acetylene molecules at 39 eV. AB - The two-body dissociation reactions of the dication, C(2)H(2)(2+), produced by 39.0 eV double photoionization of acetylene molecules, have been studied by coupling photoelectron-photoion-photoion coincidence and ion imaging techniques. The results provide the kinetic energy and angular distributions of product ions. The analysis of the results indicates that the dissociation leading to C(2)H(+)+H(+) products occurs through a metastable dication with a lifetime of 108+/-22 ns, and a kinetic energy release (KER) distribution exhibiting a maximum at ~4.3 eV with a full width at half maximum (FWHM) of about 60%. The reaction leading to CH(2)(+)+C(+) occurs in a time shorter than the typical rotational period of the acetylene molecules (of the order of 10(-12) s). The KER distribution of product ions for this reaction, exhibits a maximum at ~4.5 eV with a FWHM of about 28%. The symmetric dissociation, leading to CH(+)+CH(+), exhibits a KER distribution with a maximum at ~5.2 eV with a FWHM of 44%. For the first two reactions the angular distributions of ion products also indicate that the double photoionization of acetylene occurs when the neutral molecule is mainly oriented perpendicularly to the light polarization vector. PMID- 22667556 TI - Vibrationally averaged isotropic dispersion energy coefficients of the parahydrogen dimer. AB - We compare the sum-over-states and coupled cluster linear response formalisms for the determination of imaginary-frequency polarizabilities of H(2). Using both approaches, we compute isotropic dispersion energy coefficients C(n) (n = 6, 8, 10) for H(2)-H(2) molecular pairs over a wide range of H(2) bond lengths. We present vibrationally averaged dispersion energy coefficients for H(2)-H(2), H(2) D(2), and D(2)-D(2) molecular pairs and examine the coefficients' convergence with respect to basis set. PMID- 22667557 TI - Comprehensive vacuum ultraviolet photoionization study of the CF3(?) trifluoromethyl radical using synchrotron radiation. AB - The trifluoromethyl radical, CF(3)(?), is studied for the first time by means of threshold photoelectron spectroscopy (TPES). The radical is produced in the gas phase using the flash-pyrolysis technique from hexafluoroethane as a precursor. CF(3)(+) total ion yield and mass-selected TPES of the radical are recorded using a spectrometer based upon velocity map imaging and Wiley-McLaren time-of-flight coupled to the synchrotron radiation. The high resolution of the instrument and of the photons allows the observation of rich vibrational progressions in the TPES of CF(3)(?). By using Franck-Condon factors computed by Bowman and coworkers, we have been able to simulate the TPES. The initial vibrational temperature of the radical beam has been evaluated at 350 +/- 70 K. The structures have been identified as transitions between (n(1),n(2)) and (n(1)(+),n(2)(+)) vibrational levels of CF(3) and CF(3)(+) with small excitation of the breathing mode, nu(1)(+) (,) and large excitation (n(2)(+) = 10-26) of the umbrella mode, nu(2)(+), in the cation. From the energy separation between the two resolved peaks of each band, a value of 994 +/- 16 cm(-1) has been derived for the nu(1)(+) breathing frequency of CF(3)(+). For the high-lying n(2)(+) levels, the apparent nu(2)(+) umbrella spacing, 820 +/- 14 cm(-1), is fairly constant. Taking into account the nu(2)(+) anharmonicity calculated by Bowman and coworkers, we have deduced nu(2)(+) = 809 +/- 14 cm(-1), and semi-empirical estimations of the adiabatic ionization energy IE(ad.)(CF(3)(?)) are proposed in good agreement with most of previous works. A value of the vertical ionization potential, IE(vert.)(CF(3)(?)) = 11.02 eV, has been derived from the observation of a photoelectron spectrum recorded at a fixed photon energy of 12 eV. PMID- 22667558 TI - Imaging ion-molecule reactions: charge transfer and C-N bond formation in the C(+) + NH3 system. AB - The velocity mapping ion imaging method is applied to the ion-molecule reactions occurring between C(+) and NH(3). The velocity space images are collected over the relative collision energy range from 1.5 to 3.3 eV, allowing both product kinetic energy distributions and angular distributions to be obtained from the data. The charge transfer process appears to be direct, dominated by long-range electron transfer that results in minimal deflection of the products. The product kinetic energy distributions are consistent with a process dominated by energy resonance. The kinetic energy distributions for C-N bond formation appear to scale with the total available energy, providing strong evidence that energy in the [CNH(3)](+) precursor to products is distributed statistically. The angular distributions for C-N bond formation show pronounced forward-backward symmetry, as expected for a complex that resembles a prolate symmetric top decaying along its symmetry axis. PMID- 22667559 TI - Behavior of rate coefficients for ion-ion mutual neutralization, 300-550 K. AB - Rate coefficients k(MN) have been measured for a number of anion neutralization reactions with Ar(+) and Kr(+) over the temperature range 300-550 K. For the first time, the data set includes anions of radicals and other short-lived species. In the present paper, we review these results and make note of correlations with reduced mass, electron binding energy of the anion (equivalent to the electron affinity of the corresponding neutral), and temperature, and compare with expectations from absorbing sphere models. An intriguing result is that the data for diatomic anions neutralized by Ar(+) and Kr(+) have k(MN) values close to 3 * 10(-8) cm(3) s(-1) at 300 K, a figure which is lower than those for all of the polyatomic anions at 300 K except for SF(5)(-) + Kr(+). For the polyatomic anions studied here, neutralized by Ar(+) and Kr(+), the reduced mass dependence agrees with theory, on average, but we find a stronger temperature dependence of T(-0.9) than expected from the theoretical E(-0.5) energy dependence of the rate coefficient at thermal energies. The k(MN) show a weak dependence on the electron binding energy of the anion for the polyatomic species studied. PMID- 22667560 TI - ONIOM approach for non-adiabatic on-the-fly molecular dynamics demonstrated for the backbone controlled Dewar valence isomerization. AB - Non-adiabatic on-the-fly molecular dynamics (NA-O-MD) simulations require the electronic wavefunction, energy gradients, and derivative coupling vectors in every timestep. Thus, they are commonly restricted to the excited state dynamics of molecules with up to ~20 atoms. We discuss an approximation that combines the ONIOM(QM:QM) method with NA-O-MD simulations to allow calculations for larger molecules. As a proof of principle we present the excited state dynamics of a (6 4)-lesion containing dinucleotide (63 atoms), and especially the importance to include the confinement effects of the DNA backbone. The method is able to include electron correlation on a high level of theory and offers an attractive alternative to QM:MM approaches for moderate sized systems with unknown force fields. PMID- 22667561 TI - The A-state dissociation continuum of NO-Ar and its near infrared spectrum. AB - After preparing NO-Ar in a vibrational state correlating with the first overtone vibration in NO, we recorded its hot band UV spectrum by monitoring simultaneously the intensity in the NO(+) and the NO(+)-Ar ion channels. In this way, the bound as well as the continuous part of the electronic A<-X spectrum are observed directly. Below the dissociation threshold, the intensity is found exclusively in the NO(+)-Ar ion channel while above it is found in the NO fragment ion channel. We observe simultaneously intensity in both ion channels only for a very narrow frequency range near the dissociation threshold. Structures in the dissociation spectrum correlate well with the thresholds for production of NO(A) in different rotational states. At frequencies well above the dissociation threshold, NO-Ar is detected efficiently as a NO fragment. This fact has been exploited to record the near IR spectrum of NO-Ar with significantly increased sensitivity. The dissociation detected spectra are essentially identical to our previous constant photon energy sum (CONPHOENERS) scans [B. Wen, Y. Kim, H. Meyer, J. Klos, and M. H. Alexander, J. Phys. Chem. A 112, 9483 (2008)]. Several hot band spectra have been remeasured with improved sensitivity enabling a comprehensive analysis yielding for the first time spectroscopic constants for levels associated with the potential surfaces of NO-Ar correlating with NO(v(NO) = 0 and 2). Since many NO-X complexes do not have a strong bound A state spectrum, although they do have a A-state dissociation continuum, there is the possibility to record their near IR spectra by employing dissociation detection. PMID- 22667562 TI - Hydrogen scrambling in ethane induced by intense laser fields: statistical analysis of coincidence events. AB - Two-body Coulomb explosion processes of ethane (CH(3)CH(3)) and its isotopomers (CD(3)CD(3) and CH(3)CD(3)) induced by an intense laser field (800 nm, 1.0 * 10(14) W/cm(2)) with three different pulse durations (40 fs, 80 fs, and 120 fs) are investigated by a coincidence momentum imaging method. On the basis of statistical treatment of the coincidence data, the contributions from false coincidence events are estimated and the relative yields of the decomposition pathways are determined with sufficiently small uncertainties. The branching ratios of the two body decomposition pathways of CH(3)CD(3) from which triatomic hydrogen molecular ions (H(3)(+), H(2)D(+), HD(2)(+), D(3)(+)) are ejected show that protons and deuterons within CH(3)CD(3) are scrambled almost statistically prior to the ejection of a triatomic hydrogen molecular ion. The branching ratios were estimated by statistical Rice-Ramsperger-Kassel-Marcus calculations by assuming a transition state with a hindered-rotation of a diatomic hydrogen moiety. The hydrogen scrambling dynamics followed by the two body decomposition processes are discussed also by using the anisotropies in the ejection directions of the fragment ions and the kinetic energy distribution of the two body decomposition pathways. PMID- 22667563 TI - Control and femtosecond time-resolved imaging of torsion in a chiral molecule. AB - We study how the combination of long and short laser pulses can be used to induce torsion in an axially chiral biphenyl derivative (3,5-difluoro-3',5'-dibromo-4' cyanobiphenyl). A long, with respect to the molecular rotational periods, elliptically polarized laser pulse produces 3D alignment of the molecules, and a linearly polarized short pulse initiates torsion about the stereogenic axis. The torsional motion is monitored in real-time by measuring the dihedral angle using femtosecond time-resolved Coulomb explosion imaging. Within the first 4 picoseconds (ps), torsion occurs with a period of 1.25 ps and an amplitude of 3 degrees in excellent agreement with theoretical calculations. At larger times, the quantum states of the molecules describing the torsional motion dephase and an almost isotropic distribution of the dihedral angle is measured. We demonstrate an original application of covariance analysis of two-dimensional ion images to reveal strong correlations between specific ejected ionic fragments from Coulomb explosion. This technique strengthens our interpretation of the experimental data. PMID- 22667564 TI - High-spin electronic states of lanthanide-arene complexes: Nd(benzene) and Nd(naphthalene). AB - Neodymium (Nd) complexes of benzene and naphthalene were synthesized in a laser ablation supersonic molecular beam source. High-resolution electron spectra of these complexes were obtained using pulsed-field ionization zero electron kinetic energy (ZEKE) spectroscopy. Second-order Moller-Plesset perturbation calculations were employed to aid spectral and electronic-state assignments. The adiabatic ionization energies were measured to be 38 081 (5) cm(-1) for Nd(benzene) and 37 815 (5) cm(-1) for Nd(naphthalene). For the Nd(benzene) complex, the observed frequencies of 831 and 286 cm(-1) were assigned to C-H out-of-plane bending and Nd(+)-C(6)H(6) stretching modes in the (6)A(1) ion state and 256 cm(-1) to the Nd C(6)H(6) stretching mode in the (7)A(1) neutral state. To confirm these assignments, the ZEKE spectrum of the deuterated species was recorded, and the corresponding vibrational frequencies were measured to be 710 and 277 cm(-1) in the ion state and 236 cm(-1) in the neutral state. For the Nd(naphthalene) complex, the observed vibrational modes were C(10)H(8) bending (394 cm(-1)), Nd(+)-C(10)H(8) stretching (286 and 271 cm(-1)), Nd(+)-C(10)H(8) bending (80 cm( 1)), and C(10)H(8) twisting (105 cm(-1)) in the (6)A(') ion state and metal ligand bending (60 cm(-1)) and ligand twisting (55 cm(-1)) in the (7)A(') neutral state. The formation of the ground state of the Nd(benzene) complex requires 4f > 5d and 6s -> 5d electron excitation of the Nd atom, whereas the formation of the ground state of Nd(naphthalene) involves the 6s -> 5d electron promotion. PMID- 22667565 TI - Density and birefringence of a highly stable alpha,alpha,beta-trisnaphthylbenzene glass. AB - Spectroscopic ellipsometry has been used to understand the properties of alpha,alpha,beta-trisnaphthylbenzene (alphaalphabeta-TNB) glasses vapor-deposited at a substrate temperature of 295 K (0.85 T(g)). In a single temperature ramping experiment, a range of properties of the as-deposited glass can be measured, including density, fictive temperature, onset temperature, thermal expansion coefficient, and birefringence. The vapor-deposited alphaalphabeta-TNB glass is 1.3% more dense than the ordinary glass prepared by cooling at 1 K/min, is found to be birefringent, has a fictive temperature 35 K below that of the ordinary glass, and an onset temperature 20 K above that of the ordinary glass. The thermal expansion coefficient of the vapor-deposited alphaalphabeta-TNB glass is 14% lower than that of the ordinary glass, indicating that lower portions of the potential energy landscape have more harmonic potential minima than the parts accessible to the ordinary glass. PMID- 22667566 TI - Dynamic relaxation of a liquid cavity under amorphous boundary conditions. AB - The growth of cooperatively rearranging regions was invoked long ago by Adam and Gibbs to explain the slowing down of glass-forming liquids. The lack of knowledge about the nature of the growing order, though, complicates the definition of an appropriate correlation function. One option is the point-to-set (PTS) correlation function, which measures the spatial span of the influence of amorphous boundary conditions on a confined system. By using a swap Monte Carlo algorithm we measure the equilibration time of a liquid droplet bounded by amorphous boundary conditions in a model glass-former at low temperature, and we show that the cavity relaxation time increases with the size of the droplet, saturating to the bulk value when the droplet outgrows the point-to-set correlation length. This fact supports the idea that the point-to-set correlation length is the natural size of the cooperatively rearranging regions. On the other hand, the cavity relaxation time computed by a standard, nonswap dynamics, has the opposite behavior, showing a very steep increase when the cavity size is decreased. We try to reconcile this difference by discussing the possible hybridization between mode-coupling theory and activated processes, and by introducing a new kind of amorphous boundary conditions, inspired by the concept of frozen external state as an alternative to the commonly used frozen external configuration. PMID- 22667567 TI - Ultrafast photo-induced charge transfer unveiled by two-dimensional electronic spectroscopy. AB - The interaction of exciton and charge transfer (CT) states plays a central role in photo-induced CT processes in chemistry, biology, and physics. In this work, we use a combination of two-dimensional electronic spectroscopy (2D-ES), pump probe measurements, and quantum chemistry to investigate the ultrafast CT dynamics in a lutetium bisphthalocyanine dimer in different oxidation states. It is found that in the anionic form, the combination of strong CT-exciton interaction and electronic asymmetry induced by a counter-ion enables CT between the two macrocycles of the complex on a 30 fs timescale. Following optical excitation, a chain of electron and hole transfer steps gives rise to characteristic cross-peak dynamics in the electronic 2D spectra, and we monitor how the excited state charge density ultimately localizes on the macrocycle closest to the counter-ion within 100 fs. A comparison with the dynamics in the radical species further elucidates how CT states modulate the electronic structure and tune fs-reaction dynamics. Our experiments demonstrate the unique capability of 2D-ES in combination with other methods to decipher ultrafast CT dynamics. PMID- 22667568 TI - The electronic structure of free aluminum clusters: metallicity and plasmons. AB - The electronic structure of free aluminum clusters with ~3-4 nm radius has been investigated using synchrotron radiation-based photoelectron and Auger electron spectroscopy. A beam of free clusters has been produced using a gas-aggregation source. The 2p core level and the valence band have been probed. Photoelectron energy-loss features corresponding to both bulk and surface plasmon excitation following photoionization of the 2p level have been observed, and the excitation energies have been derived. In contrast to some expectations, the loss features have been detected at energies very close to those of the macroscopic solid. The results are discussed from the point of view of metallic properties in nanoparticles with a finite number of constituent atoms. PMID- 22667569 TI - Rotational dynamics in supercooled water from nuclear spin relaxation and molecular simulations. AB - Structural dynamics in liquid water slow down dramatically in the supercooled regime. To shed further light on the origin of this super-Arrhenius temperature dependence, we report high-precision (17)O and (2)H NMR relaxation data for H(2)O and D(2)O, respectively, down to 37 K below the equilibrium freezing point. With the aid of molecular dynamics (MD) simulations, we provide a detailed analysis of the rotational motions probed by the NMR experiments. The NMR-derived rotational correlation time tau(R) is the integral of a time correlation function (TCF) that, after a subpicosecond librational decay, can be described as a sum of two exponentials. Using a coarse-graining algorithm to map the MD trajectory on a continuous-time random walk (CTRW) in angular space, we show that the slowest TCF component can be attributed to large-angle molecular jumps. The mean jump angle is ~48 degrees at all temperatures and the waiting time distribution is non exponential, implying dynamical heterogeneity. We have previously used an analogous CTRW model to analyze quasielastic neutron scattering data from supercooled water. Although the translational and rotational waiting times are of similar magnitude, most translational jumps are not synchronized with a rotational jump of the same molecule. The rotational waiting time has a stronger temperature dependence than the translation one, consistent with the strong increase of the experimentally derived product tau(R) D(T) at low temperatures. The present CTRW jump model is related to, but differs in essential ways from the extended jump model proposed by Laage and co-workers. Our analysis traces the super-Arrhenius temperature dependence of tau(R) to the rotational waiting time. We present arguments against interpreting this temperature dependence in terms of mode-coupling theory or in terms of mixture models of water structure. PMID- 22667570 TI - Elasticity of two-dimensional crystals of polydisperse hard disks near close packing: surprising behavior of the Poisson's ratio. AB - The equation of state, elastic constants, and Poisson's ratio of a crystalline two-dimensional polydisperse hard disk system were determined in the close packing limit. Monte Carlo simulations in the NpT ensemble with variable shape of the periodic box reveal that the pressure and elastic constants grow with increasing polydispersity. The equation of state and the bulk modulus are well described by the free volume approximation. The latter approximation fails, however, for the shear modulus. The simulations also show that the introduction of any amount of size polydispersity in the hard disk systems causes a discontinuous "jump" of the Poisson's ratio in the close packing limit from the value nu(delta=0) = 0.1308(22), obtained for equidiameter hard disks, to nu(delta>0) ~ 1, estimated for the polydisperse disks. PMID- 22667571 TI - Ultrafast formation of the benzoic acid triplet upon ultraviolet photolysis and its sequential photodissociation in solution. AB - Time-resolved infrared (TR-IR) absorption spectroscopy in both the femtosecond and nanosecond time domain has been applied to examine the photolysis of benzoic acid in acetonitrile solution following either 267 nm or 193 nm excitation. By combining the ultrafast and nanosecond TR-IR measurements, both the excited states and the photofragments have been detected and key mechanistic insights were obtained. We show that the solvent interaction modifies the excited state relaxation pathways and thus the population dynamics, leading to different photolysis behavior in solution from that observed in the gas phase. Vibrational energy transfer to solvents dissipates excitation energy efficiently, suppressing the photodissociation and depopulating the excited S(2) or S(3) state molecules to the lowest T(1) state with a rate of ~2.5 ps after a delayed onset of ~3.7 ps. Photolysis of benzoic acid using 267 nm excitation is dominated by the formation of the T(1) excited state and no photofragments could be detected. The results from TR-IR experiments using higher energy of 193 nm indicate that photodissociation proceeds more rapidly than the vibrational energy transfer to solvents and C-C bond fission becomes the dominant relaxation pathway in these experiments as featured by the prominent observation of the COOH photofragments and negligible yield of the T(1) excited state. The measured ultrafast formation of T(1) excited state supports the existence of the surface intersections of S(2)/S(1), S(2)/T(2), and S(1)/T(1)/T(2), and the large T(1) quantum yield of ~0.65 indicates the importance of the excited state depopulation to triplet manifold as the key factor affecting the photophysical and photochemical behavior of the monomeric benzoic acid. PMID- 22667572 TI - Drift velocity in non-isothermal inhomogeneous systems. AB - Drift velocity and driving force are not directly proportional in the case of inhomogeneous suspensions, where a space dependent mobility induces an additional contribution to the drift velocity. Similarly, particle flux and drift velocity are related not only by the gradient of density but also by an additional contribution given by the gradient of the self-diffusion coefficient. We provide quantitative support to this scenario in a non-equilibrium system by means of computer simulations with a temperature gradient. Moreover, our simulation results demonstrate that the temperature gradient-induced mass transport coefficient, namely thermal diffusion coefficient, is not directly proportional to the drift velocity so that the well-accepted relation of proportionality is just an approximation. PMID- 22667573 TI - Revisiting the mean-field picture of dipolar effects in solution NMR. AB - For more than three decades, the classical or mean-field picture describing the distant dipolar field has been almost always simplified to an effective field proportional to the local longitudinal magnetization, differing only by a scale factor of 1.5 for homomolecular (identical resonance frequency) and heteromolecular interactions. We re-examine the underlying assumptions, and show both theoretically and experimentally that the mathematical framework needs to be modified for modern applications such as imaging. We demonstrate new pulse sequences which produce unexpected effects; for example, modulating an arbitrarily small fraction of the magnetization can substantially alter the frequency evolution. Thus, matched gradient pulse pairs (a seemingly innocuous module in thousands of existing pulse sequences) can alter the time evolution in highly unexpected ways, particularly with small flip angle pulses such as those used in hyperpolarized experiments. We also show that specific gradient pulse combinations can retain only dipolar interactions between unlike spins, and the dipolar field can generate a secular Hamiltonian proportional to I(x). PMID- 22667574 TI - The glass transition and the distribution of voids in room-temperature ionic liquids: a molecular dynamics study. AB - The glass transition in prototypical room temperature ionic liquids has been investigated by molecular dynamics simulations based on an Amber-like empirical force field. Samples of [C(4)mim][PF(6)], [C(4)mim][Tf(2)N], and [C(3)mim][Tf(2)N] have been quenched from the liquid phase at T = 500 to a glassy state at T ~ 0 K in discontinuous steps of 20 K every 1.2 ns. The glass temperature estimated by simulation (T(g) = 209 K for [C(4)mim][PF(6)], T(g) = 204 K for [C(4)mim][Tf(2)N], and T(g) = 196 K for [C(3)mim][Tf(2)N]) agrees semi quantitatively with the experimental values (T(g) = 193/196 K for [C(4)mim][PF(6)], T(g) = 186/189 K for [C(4)mim][Tf(2)N], and T(g) = 183 K for [C(3)mim][Tf(2)N]). A model electron density is introduced to identify voids in the system. The temperature dependence of the size distribution of voids provided by simulation reproduce well the experimental results of positron annihilation lifetime spectroscopy reported in G. Dlubek, Y. Yu, R. Krause-Rehberg, W. Beichel, S. Bulut, N. Pogodina, I. Krossing, and Ch. Friedrich, J. Chem. Phys. 133, 124502 (2010), with only one free parameter needed to fit the experimental data. PMID- 22667575 TI - Fluorescence quenching near small metal nanoparticles. AB - We develop a microscopic model for fluorescence of a molecule (or semiconductor quantum dot) near a small metal nanoparticle. When a molecule is situated close to metal surface, its fluorescence is quenched due to energy transfer to the metal. We perform quantum-mechanical calculations of energy transfer rates for nanometer-sized Au nanoparticles and find that nonlocal and quantum-size effects significantly enhance dissipation in metal as compared to those predicted by semiclassical electromagnetic models. However, the dependence of transfer rates on molecule's distance to metal nanoparticle surface, d, is significantly weaker than the d(-4) behavior for flat metal surface with a sharp boundary predicted by previous calculations within random phase approximation. PMID- 22667576 TI - Steady-state nucleation rate and flux of composite nucleus at saddle point. AB - The steady-state nucleation rate and flux of composite nucleus at the saddle point is studied by extending the theory of binary nucleation. The Fokker-Planck equation that describes the nucleation flux is derived using the Master equation for the growth of the composite nucleus, which consists of the core of the final stable phase surrounded by a wetting layer of the intermediate metastable phase nucleated from a metastable parent phase recently evaluated by Iwamatsu [J. Chem. Phys. 134, 164508 (2011)]. The Fokker-Planck equation is similar to that used in the theory of binary nucleation, but the non-diagonal elements exist in the reaction rate matrix. First, the general solution for the steady-state nucleation rate and the direction of nucleation flux is derived. Next, this information is then used to study the nucleation of composite nucleus at the saddle point. The dependence of steady-state nucleation rate as well as the direction of nucleation flux on the reaction rate in addition to the free-energy surface is studied using a model free-energy surface. The direction of nucleation current deviates from the steepest-descent direction of the free-energy surface. The results show the importance of two reaction rate constants: one from the metastable environment to the intermediate metastable phase and the other from the metastable intermediate phase to the stable new phase. On the other hand, the gradient of the potential Phi or the Kramers crossover function (the commitment or splitting probability) is relatively insensitive to reaction rates or free-energy surface. PMID- 22667577 TI - Functional K-doping of eumelanin thin films: Density functional theory and soft x ray spectroscopy experiments in the frame of the macrocyclic protomolecule model [corrected]. AB - We demonstrate the possibility to achieve the doping of eumelanin thin films through K(+) incorporation during the electrodeposition of the film. K-doping changes the optical properties of the eumelanin thin films, reducing the energy gap from 1.0 to 0.6 eV, with possible implications for the photophysical properties. We have identified the doping-related occupied and unoccupied electronic states and their spectral weight using resonant photoemission spectroscopy (ResPES) and x-ray absorption at the C and N K-edges (near edge x ray absorption fine spectroscopy, NEXAFS). All data are consistently interpreted by ab initio calculations of the electronic structure within the frame of the macrocycle model developed for the eumelanin protomolecule. Our analysis puts in evidence the intercalation of K with one specific oligomer (a tetramer composed of one indolequinone and 3 hydroquinone monomers) in correspondence of the nitrogen macrocycle. The predicted variation of the tetramer spacing is also in agreement with the recent x-ray diffraction experiments. The charge donation from K to N and C atoms gives rise to new electronic states at the top of the valence band and in NEXAFS resonances of the unoccupied orbitals. The saturation of the tetramer macrocycles leaves an excess of K that bind to N and C atoms in alternative configurations, as witnessed by the occurrence of additional spectral features in the carbon-related ResPES measurements. PMID- 22667578 TI - One-particle correlation function in evanescent wave dynamic light scattering. AB - In order to interpret measured intensity autocorrelation functions obtained in evanescent wave scattering, their initial decay rates have been analyzed recently [P. Holmqvist, J. K. G. Dhont, and P. R. Lang, Phys. Rev. E 74, 021402 (2006); B. Cichocki, E. Wajnryb, J. Blawzdziewicz, J. K. G. Dhont, and P. R. Lang, J. Chem. Phys. 132, 074704 (2010); J. W. Swan and J. F. Brady, ibid. 135, 014701 (2011)]. A theoretical analysis of the longer time dependence of evanescent wave autocorrelation functions, beyond the initial decay, is still lacking. In this paper we present such an analysis for very dilute suspensions of spherical colloids. We present simulation results, a comparison to cumulant expansions, and experiments. An efficient simulation method is developed which takes advantage of the particular mathematical structure of the time-evolution equation of the probability density function of the position coordinate of the colloidal sphere. The computer simulation results are compared with analytic, first and second order cumulant expansions. The only available analytical result for the full time dependence of evanescent wave autocorrelation functions [K. H. Lan, N. Ostrowsky, and D. Sornette, Phys. Rev. Lett. 57, 17 (1986)], that neglects hydrodynamic interactions between the colloidal spheres and the wall, is shown to be quite inaccurate. Experimental results are presented and compared to the simulations and cumulant expansions. PMID- 22667579 TI - CO adsorption and desorption on size-selected Pd(n)/TiO2(110) model catalysts: size dependence of binding sites and energies, and support-mediated adsorption. AB - The nature of CO adsorption on Pd(n)/TiO(2)(110) (n = 1, 2, 7, 20) has been examined using temperature-programmed desorption (TPD), temperature-dependent helium ion scattering (TD-ISS), and X-ray photoelectron spectroscopy (XPS). All samples contain the same number of Pd atoms (0.10 ML-equivalent) deposited as different size clusters. The TPD and TD-ISS show that CO binds in two types of sites associated with the Pd clusters. The most stable sites are on top of the Pd clusters ("on-top" sites), however, there are also less stable sites, in which CO is bound in association with, but not on top of the Pd ("peripheral" sites). For saturation CO coverage over a fixed atomic concentration of Pd (present in the form of Pd(n) clusters of varying size), the population of CO in peripheral sites decreases with increasing cluster size, while the on-top site population is size independent. This is consistent with what geometric considerations would predict for the density of the two types of sites, provided the clusters adsorb predominantly as 2D islands, which ISS results suggest to be the case. The XPS analysis indicates that CO-Pd binding is dominated by pi-backbonding to the Pd(n) clusters. The results also show evidence for efficient support-mediated adsorption (reverse-spillover) of CO initially impinging on TiO(2) to binding sites associated with the Pd clusters. PMID- 22667580 TI - Effects of intermolecular interaction on the energy distribution of valance electronic states of a carbazole-based material in amorphous thin films. AB - Effects of intermolecular interactions on the occupied electronic structure of amorphous solid of a carbazole-based material were investigated under an assumption that the organic solid consists of randomly oriented assemblies of dimers. The electronic energy states were calculated on the ensemble of large number of random dimers, of which geometries are relaxed using semiempirical van der Waals density functional theory. Intermolecular interactions result in splitting of energy level, and further disorders occur by aggregation of randomly orientated molecules. As a result, frontier occupied energy states can be represented by a superposition of Gaussian distributions, including (i) a main distribution with full width at half maximum of 80-110 meV, depending on the methods of relaxation and (ii) shoulders separated from the center of the main distribution with a value as large as 150 meV. A possible origin for the appearance of these shoulders was ascribed to the presence of molecular assemblies consisting of more tightly bound dimers compared with the others. PMID- 22667581 TI - Semiclassical perturbation theory for diffraction in heavy atom surface scattering. AB - The semiclassical perturbation theory formalism of Hubbard and Miller [J. Chem. Phys. 78, 1801 (1983)] for atom surface scattering is used to explore the possibility of observation of heavy atom diffractive scattering. In the limit of vanishing h the semiclassical theory is shown to reduce to the classical perturbation theory. The quantum diffraction pattern is sensitive to the characteristics of the beam of incoming particles. Necessary conditions for observation of quantum diffraction are derived for the angular width of the incoming beam. An analytic expression for the angular distribution as a function of the angular and momentum variance of the incoming beam is obtained. We show both analytically and through some numerical results that increasing the angular width of the incident beam leads to decoherence of the quantum diffraction peaks and one approaches the classical limit. However, the incoherence of the beam in the parallel direction does not destroy the diffraction pattern. We consider the specific example of Ar atoms scattered from a rigid LiF(100) surface. PMID- 22667582 TI - Momentum dependence of the excitons in pentacene. AB - We have carried out electron energy-loss investigations of the lowest singlet excitons in pentacene at 20 K. Our studies allow to determine the full exciton band structure in the a*, b* reciprocal lattice plane. The lowest singlet exciton can move coherently within this plane, and the resulting exciton dispersion is highly anisotropic. The analysis of the energetically following (satellite) features indicates a strong admixture of charge transfer excitations to the exciton wave function. PMID- 22667583 TI - Chain-length dependent growth dynamics of n-alkanes on silica investigated by energy-dispersive x-ray reflectivity in situ and in real-time. AB - We compare the growth dynamics of the three n-alkanes C(36)H(74), C(40)H(82), and C(44)H(90) on SiO(2) using real-time and in situ energy-dispersive x-ray reflectivity. All molecules investigated align in an upright-standing orientation on the substrate and exhibit a transition from layer-by-layer growth to island growth after about 4 monolayers under the conditions employed. Simultaneous fits of the reflected intensity at five distinct points in reciprocal space show that films formed by longer n-alkanes roughen faster during growth. This behavior can be explained by a chain-length dependent height of the Ehrlich-Schwoebel barrier. Further x-ray diffraction measurements after growth indicate that films consisting of longer n-alkanes also incorporate more lying-down molecules in the top region. While the results reveal behavior typical for chain-like molecules, the findings can also be useful for the optimization of organic field effect transistors where smooth interlayers of n-alkanes without coexistence of two or more molecular orientations are required. PMID- 22667584 TI - A density functional study of C1-C4 alkyl adsorption on Cu(111). AB - To better understand the nature of alkyl intermediates often invoked in reactions involving hydrocarbon reactants and products, the adsorption of linear and branched C(1)-C(4) alkyls on Cu(111) at 1/4 ML and 1/9 ML coverages was studied using density functional theory. The adsorption energy and site preference are found to be coverage-dependent, and both direct alkyl-alkyl interactions and changes in the Cu electronic structure play a role in these trends. It was found that methyl strongly prefers the hollow sites, the branched alkyls strongly prefer the top site, and the linear C(2)-C(4) alkyls have weak site preferences that change with coverage. To explain these differences, rationalize alkyl adsorption trends, and predict the binding energy of other alkyls, a simple model was developed in which the binding energy is fit as a linear function of the number of C-Cu and C-H-Cu interactions as well as the C-H bond energy in the corresponding alkane. Site preference can be understood as a compromise between C Cu interactions and C-H-Cu interactions. Density of states analysis was used to gain a molecular-orbital understanding of the bonding of alkyls to Cu(111). PMID- 22667585 TI - Driven Brownian coagulation of polymers. AB - We present an analysis of the mean-field kinetics of Brownian coagulation of droplets and polymers driven by input of monomers which aims to characterize the long time behavior of the cluster size distribution as a function of the inverse fractal dimension, a, of the aggregates. We find that two types of long time behavior are possible. For 0<=a<1/2 the size distribution reaches a stationary state with a power law distribution of cluster sizes having exponent 3/2. The amplitude of this stationary state is determined exactly as a function of a. For 1/295% efficiency and projects each IR channel image side-by-side on the camera's detector. Cutoff filters are used in each IR channel, and ZnSe imaging optics and mirrors optimized for broadband IR use are incorporated into the design. In-situ and ex-situ temperature calibration and preliminary data of the NSTX divertor during plasma discharges are presented, with contrasting results for dual-band vs. single-band IR operation. PMID- 22667625 TI - Designing a miniaturised heated stage for in situ optical measurements of solid oxide fuel cell electrode surfaces, and probing the oxidation of solid oxide fuel cell anodes using in situ Raman spectroscopy. AB - A novel miniaturised heated stage for in operando optical measurements on solid oxide fuel cell electrode surfaces is described. The design combines the advantages of previously reported designs, namely, (i) fully controllable dual atmosphere operation enabling fuel cell pellets to be tested in operando with either electrode in any atmosphere being the focus of study, and (ii) combined electrochemical measurements with optical spectroscopy measurements with the potential for highly detailed study of electrochemical processes; with the following advances, (iii) integrated fitting for mounting on a mapping stage enabling 2-D spatial characterisation of the surface, (iv) a compact profile that is externally cooled, enabling operation on an existing microscope without the need for specialized lenses, (v) the ability to cool very rapidly, from 600 degrees C to 300 degrees C in less than 5 min without damaging the experimental apparatus, and (vi) the ability to accommodate a range of pellet sizes and thicknesses. PMID- 22667626 TI - Optimal design and fabrication of three-dimensional calibration specimens for scanning probe microscopy. AB - Micro-/nano-scale roughness specimens are highly demanded to synthetically calibrate the scanning probe microscopy (SPM) instrument. In this study, three dimensional (3D) specimens with controllable main surface evaluation parameters were designed. In order to improve the design accuracy, the genetic algorithm was introduced into the conventional digital filter method. A primary 3D calibration specimen with the dimension of 10 MUm * 10 MUm was fabricated by electron beam lithography. Atomic force microscopy characterizations demonstrated that the statistical and spectral parameters of the fabricated specimen match well with the designed values. Such a kind of 3D specimens has the potential to calibrate the SPM for applications in quantitative surface evaluations. PMID- 22667627 TI - A furnace with rotating load frame for in situ high temperature deformation and creep experiments in a neutron diffraction beam line. AB - A resistive furnace combined with a load frame was built that allows for in situ neutron diffraction studies of high temperature deformation, in particular, creep. A maximum force of 2700 N can be applied at temperatures up to 1000 degrees C. A load control mode permits studies of, e.g., creep or phase transformations under applied uni-axial stress. In position control, a range of high temperature deformation experiments can be achieved. The examined specimen can be rotated up to 80 degrees around the vertical compression axis allowing texture measurements in the neutron time-of-flight diffractometer HIPPO (High Pressure - Preferred Orientation). We present results from the successful commissioning, deforming a Zr-2.5 wt.% Nb cylinder at 975 degrees C. The device is now available for the user program of the HIPPO diffractometer at the LANSCE (Los Alamos Neutron Science Center) user facility. PMID- 22667628 TI - Development of a simultaneous Hugoniot and temperature measurement for preheated metal shock experiments: melting temperatures of Ta at pressures of 100 GPa. AB - Equations of state of metals are important issues in earth science and planetary science. A major limitation of them is the lack of experimental data for determining pressure-volume and temperature of shocked metal simultaneously. By measuring them in a single experiment, a major source of systematic error is eliminated in determining from which shock pressure release pressure originates. Hence, a non-contact fast optical method was developed and demonstrated to simultaneously measure a Hugoniot pressure-volume (P(H)-V(H)) point and interfacial temperature T(R) on the release of Hugoniot pressure (P(R)) for preheated metals up to 1000 K. Experimental details in our investigation are (i) a Ni-Cr resistance coil field placed around the metal specimen to generate a controllable and stable heating source, (ii) a fiber-optic probe with an optical lens coupling system and optical pyrometer with ns time resolution to carry out non-contact fast optical measurements for determining P(H)-V(H) and T(R). The shock response of preheated tantalum (Ta) at 773 K was investigated in our work. Measured data for shock velocity versus particle velocity at an initial state of room temperature was in agreement with previous shock compression results, while the measured shock data between 248 and 307 GPa initially heated to 773 K were below the Hugoniot evaluation from its off-Hugoniot states. Obtained interfacial temperatures on release of Hugoniot pressures (100-170 GPa) were in agreement with shock-melting points at initial ambient condition and ab initio calculations of melting curve. It indicates a good consistency for shock melting data of Ta at different initial temperatures. Our combined diagnostics for Hugoniot and temperature provides an important approach for studying EOS and the temperature effect of shocked metals. In particular, our measured melting temperatures of Ta address the current controversy about the difference by more than a factor of 2 between the melting temperatures measured under shock and those measured in a laser-heated diamond anvil cell at ~100 GPa. PMID- 22667629 TI - Stencil mask methodology for the parallelized production of microscale mechanical test samples. AB - A new methodology to parallelize the production of micromechanical test samples from bulk materials is reported. This methodology has been developed to produce samples with typical gage dimensions on the order of 20-200 MUm, and also to minimize the reliance on conventional focused ion beam fabrication methods. The fabrication technique uses standard microelectronic process methods such as photolithography and deep-reactive ion etching to create high aspect ratio patterned templates-stencil masks-from a silicon wafer. In the present work, the stencil mask pattern consists of a linear row of tensile samples, where one grip of each sample is integrally attached to the bulk substrate. Once fabricated, the stencil mask is placed on top of a pre-thinned substrate, and the pattern and substrate are co-sputtered using a broad ion beam milling system, which ultimately results in the transfer of the mask pattern into the substrate. The methodology is demonstrated using a Si stencil mask and a polycrystalline Ni foil to manufacture an array of metallic micro-tensile samples. PMID- 22667630 TI - A full Stokes vector ellipsometry measurement system for in situ diagnostics in dynamic experiments. AB - A fast ellipsometry system with a resolution of only a few nanoseconds that can simultaneously measure all four Stokes parameters was developed for use in dynamic experiments. Due to its fine temporal resolution, the system is useful for a wide variety of dynamic setups, two of which are presented, fast foil heating and shock compression. As a test case the optical properties of nickel were measured in a fast foil heating setup. The complex index of refraction and emissivity at 532 nm and in the range of 1000-1900 K are presented. It was found that the emissivity monotonously increases below and above the melting point while an abrupt increase of about 2% was observed at the phase transition. These results are in accordance with the literature. Shock compression experiments included sample-free surface measurements. Samples of 1020 steel were shocked up to 25 GPa on the Hugoniot curve. The measured optical properties under these conditions showed a significant change; the value of the emissivity was doubled. PMID- 22667631 TI - High-force NdFeB-based magnetic tweezers device optimized for microrheology experiments. AB - We present the design, calibration, and testing of a magnetic tweezers device that employs two pairs of permanent neodymium iron boron magnets surrounded by low-carbon steel focusing tips to apply large forces to soft materials for microrheology experiments. Our design enables the application of forces in the range of 1-1800 pN to ~4.5 MUm paramagnetic beads using magnet-bead separations in the range of 0.3-20 mm. This allows the use of standard coverslips and sample geometries. A high speed camera, custom LED-based illumination scheme, and mechanically stabilized measurement platform are employed to enable the measurement of materials with viscoelastic moduli as high as ~1 kPa. PMID- 22667632 TI - Magnetic measurements at pressures above 10 GPa in a miniature ceramic anvil cell for a superconducting quantum interference device magnetometer. AB - A miniature ceramic anvil high pressure cell (mCAC) was earlier designed by us for magnetic measurements at pressures up to 7.6 GPa in a commercial superconducting quantum interference magnetometer [N. Tateiwa et al., Rev. Sci. Instrum. 82, 053906 (2011)]. Here, we describe methods to generate pressures above 10 GPa in the mCAC. The efficiency of the pressure generation is sharply improved when the Cu-Be gasket is sufficiently preindented. The maximum pressure for the 0.6 mm culet anvils is 12.6 GPa when the Cu-Be gasket is preindented from the initial thickness of 300-60 MUm. The 0.5 mm culet anvils were also tested with a rhenium gasket. The maximum pressure attainable in the mCAC is about 13 GPa. The present cell was used to study YbCu(2)Si(2) which shows a pressure induced transition from the non-magnetic to magnetic phases at 8 GPa. We confirm a ferromagnetic transition from the dc magnetization measurement at high pressure. The mCAC can detect the ferromagnetic ordered state whose spontaneous magnetic moment is smaller than 1 MU(B) per unit cell. The high sensitivity for magnetic measurements in the mCAC may result from the simplicity of cell structure. The present study shows the availability of the mCAC for precise magnetic measurements at pressures above 10 GPa. PMID- 22667633 TI - Design of a continuous-flow reactor for in situ x-ray absorption spectroscopy of solids in supercritical fluids. AB - This paper presents the design and performance of a novel high-temperature and high-pressure continuous-flow reactor, which allows for x-ray absorption spectroscopy or diffraction in supercritical water and other fluids under high pressure and temperature. The in situ cell consists of a tube of sintered, polycrystalline aluminum nitride, which is tolerant to corrosive chemical media, and was designed to be stable at temperatures up to 500 degrees C and pressures up to 30 MPa. The performance of the reactor is demonstrated by the measurement of extended x-ray absorption fine structure spectra of a carbon-supported ruthenium catalyst during the continuous hydrothermal gasification of ethanol in supercritical water at 400 degrees C and 24 MPa. PMID- 22667634 TI - Humidity-controlled preparation of frozen-hydrated biological samples for cryogenic coherent x-ray diffraction microscopy. AB - Coherent x-ray diffraction microscopy (CXDM) has the potential to visualize the structures of micro- to sub-micrometer-sized biological particles, such as cells and organelles, at high resolution. Toward advancing structural studies on the functional states of such particles, here, we developed a system for the preparation of frozen-hydrated biological samples for cryogenic CXDM experiments. The system, which comprised a moist air generator, microscope, micro-injector mounted on a micromanipulator, custom-made sample preparation chamber, and flash cooling device, allowed for the manipulation of sample particles in the relative humidity range of 20%-94%rh at 293 K to maintain their hydrated and functional states. Here, we report the details of the system and the operation procedure, including its application to the preparation of a frozen-hydrated chloroplast sample. Sample quality was evaluated through a cryogenic CXDM experiment conducted at BL29XUL of SPring-8. Taking the performance of the system and the quality of the sample, the system was suitable to prepare frozen-hydrated biological samples for cryogenic CXDM experiments. PMID- 22667635 TI - A digitally configurable measurement platform using audio cards for high resolution electronic transport studies. AB - We report on a software-defined digitally configurable measurement platform for determining electronic transport properties in nanostructures with small readout signals. By using a high-resolution audio analog-to-digital/digital-to-analog converter in a digitally compensated bridge configuration we significantly increase the measurement speed compared to established techniques and simultaneously acquire large and small signal characteristics. We characterize the performance (16 bit resolution, 100 dB dynamic range at 192 kS/s) and demonstrate the application of this measurement platform for studying the transport properties of spin-valve nanopillars, a two-terminal device that exhibits giant magnetoresistance and whose resistance can be switched between two levels by applied magnetic fields and by currents applied by the audio card. The high resolution and fast sampling capability permits rapid acquisition of deep statistics on the switching of a spin-valve nanopillar and reduces the time to acquire the basic properties of the device - a state-diagram showing the magnetic configurations as function of applied current and magnetic field - by orders of magnitude. PMID- 22667636 TI - The investigation of a compact auto-connected wire-wrapped pulsed transformer. AB - For the power conditioning circuit used to deliver power efficiently from flux compression generator (FCG) to the load with high impedance, an air-cored and wire-wrapped transformer convenient in coaxial connection to the other parts is investigated. To reduce the size and enhance the performance, an auto-connection is adopted. A fast and simple model is used to calculate the electrical parameters of the transformer. To evaluate the high voltage capability, the voltages across turns and the electric field distribution in the transformer are investigated. The calculated and the measured electrical parameters of the transformer show good agreements. And the safe operating voltage is predicted to exceed 500 kV. In the preliminary experiments, the transformer is tested in a power conditioning circuit with a capacitive power supply. It is demonstrated that the output voltage of the transformer reaches -342 kV under the input voltage of -81 kV. PMID- 22667637 TI - Compact inductive energy storage pulse power system. AB - An inductive energy storage pulse power system is being developed in BARC, India. Simple, compact, and robust opening switches, capable of generating hundreds of kV, are key elements in the development of inductive energy storage pulsed power sources. It employs an inductive energy storage and opening switch power conditioning techniques with high energy density capacitors as the primary energy store. The energy stored in the capacitor bank is transferred to an air cored storage inductor in 5.5 MUs through wire fuses. By optimizing the exploding wire parameters, a compact, robust, high voltage pulse power system, capable of generating reproducibly 240 kV, is developed. This paper presents the full details of the system along with the experimental data. PMID- 22667638 TI - Development of a continuous testing apparatus for temperature reduction performance of cool coatings. AB - The working principle of a continuous testing apparatus for the temperature reduction performance of cool coatings is presented in this work. The apparatus consists of infrared reflector type lamps, an adiabatic box, and a data acquisition system. It was calibrated with the different conventional reference panels. The tests for dynamic and steady state temperature reduction performances were illustrated with two cool coatings. Results obtained directly from the simultaneous measurement are in good agreement with those calculated from separate measurements, thus confirming this apparatus as a valuable experimental tool for research and development of cool coatings. PMID- 22667639 TI - Highly sensitive thermal conductivity measurements of suspended membranes (SiN and diamond) using a 3omega-Volklein method. AB - A suspended system for measuring the thermal properties of membranes is presented. The sensitive thermal measurement is based on the 3omega dynamic method coupled to a Volklein geometry. The device obtained using micro-machining processes allows the measurement of the in-plane thermal conductivity of a membrane with a sensitivity of less than 10 nW/K (+/-5 * 10(-3) Wm(-1) K(-1) at room temperature) and a very high resolution (DeltaK/K = 10(-3)). A transducer (heater/thermometer) centered on the membrane is used to create an oscillation of the heat flux and to measure the temperature oscillation at the third harmonic using a Wheatstone bridge set-up. Power as low as 0.1 nW has been measured at room temperature. The method has been applied to measure thermal properties of low stress silicon nitride and polycrystalline diamond membranes with thickness ranging from 100 nm to 400 nm. The thermal conductivity measured on the polycrystalline diamond membrane support a significant grain size effect on the thermal transport. PMID- 22667640 TI - A thermal porosimetry method to estimate pore size distribution in highly porous insulating materials. AB - Standard pore size determination methods such as mercury porosimetry, nitrogen sorption, microscopy, or x-ray tomography are not always applicable to highly porous, low density, and thus very fragile materials. For this kind of materials, a method based on thermal characterization is proposed. Indeed, the thermal conductivity of a highly porous and insulating medium is significantly dependent on the thermal conductivity of the interstitial gas that depends on both gas pressure and size of the considered pore (Knudsen effect). It is also possible to link the pore size with the thermal conductivity of the medium. Thermal conductivity measurements are realized on specimens placed in an enclosure where the air pressure is successively set to different values varying from 10(-1) to 10(5) Pa. Knowing the global porosity ratio, an effective thermal conductivity model for a two-phase air-solid material based on a combined serial-parallel model is established. Pore size distribution can be identified by minimizing the sum of the quadratic differences between measured values and modeled ones. The results of the estimation process are the volume fractions of the chosen ranges of pore size. In order to validate the method, measurements done on insulating materials are presented. The results are discussed and show that pore size distribution estimated by the proposed method is coherent. PMID- 22667641 TI - The thermal flash technique: the inconsequential effect of contact resistance and the characterization of carbon nanotube clusters. AB - This article presents a comprehensive mathematical treatment of the theory behind the thermal flash technique used to measure the thermal diffusivity of nanostructures. Analytical expressions predicting the temperature and its rate of change for various combinations of sample length and diffusivity confirmed that the presence of contact resistance between the heat sink/source or within a cluster of materials does not influence the measurement. Measurements on multi walled carbon nanotube clusters provide further experimental evidence supporting the claim that contact resistance is inconsequential to this technique and yield a thermal conductivity of 2665 W/m K, which corresponds to an isolated nanotube and not the overall cluster. PMID- 22667642 TI - Remote vibration measurement: a wireless passive surface acoustic wave resonator fast probing strategy. AB - Surface acoustic wave (SAW) resonators can advantageously operate as passive sensors which can be interrogated through a wireless link. Amongst the practical applications of such devices, structural health monitoring through stress measurement and more generally vibration characteristics of mechanical structures benefit from the ability to bury such sensors within the considered structure (wireless and battery-less). However, measurement bandwidth becomes a significant challenge when measuring wideband vibration characteristics of mechanical structures. A fast SAW resonator measurement scheme is demonstrated here. The measurement bandwidth is limited by the physical settling time of the resonator (Q/pi periods), requiring only two probe pulses through a monostatic RADAR-like electronic setup to identify the sensor resonance frequency and hence stress on a resonator acting as a strain gauge. A measurement update rate of 4800 Hz using a high quality factor SAW resonator operating in the 434 MHz Industrial, Scientific and Medical band is experimentally demonstrated. PMID- 22667643 TI - A novel driving principle by means of the parasitic motion of the microgripper and its preliminary application in the design of the linear actuator. AB - This paper presents a novel driving principle by means of the parasitic motion of the microgripper. Actuators based on this principle can realize the large displacement range and high speed easily. Also the structure can be simple. A parasitic motion principle linear actuator mainly consisting of two piezoelectric stacks, two microgrippers and a mover was designed. Experimental results indicate that at a low driving frequency of 5 Hz, large velocity over 40 MUm/s is obtained with the driving voltage of 100 V. Backward motion was observed and analyzed. Experimental results verify the feasibility of the new principle and it can be used to design new linear or rotary actuators. PMID- 22667644 TI - Tuning of nanogap size in high tensile stress silicon nitride thin films. AB - High tensile stress suspended structures are demanded for high mechanical quality factor applications. However, high tensile stress causes distortion of the original shapes by contracting, buckling, and bending the suspended structures. We demonstrate a method to compensate for the shape deformation of suspended structures due to intrinsic tensile stress after they are released. With a new design, the distance between two suspended structures after wet etch can easily be tuned by a single fabrication beyond the lithographic resolution limits. The technique is simulated by finite element analysis and experimentally implemented to demonstrate a gap tuning capability with 2.4 nm standard error. PMID- 22667645 TI - Development of a micro cell compression stimulator for evaluating real-time cellular responses. AB - This paper presents a micro cell compression stimulator for evaluating real-time cellular responses to compression stimuli. The device was produced by a micro three-dimensional structure fabrication process using multiple exposures to the photoresist. The device consists of a pressure inlet port, cell inlet ports, a gasket, microchannels, cell culture chambers, and a diaphragm on the culture chamber for applying compressive pressure to cells. Compression stimuli applied to the cells can be controlled by regulating the expansion of the diaphragm via a pressure control. The device permits the observation of cellular responses to compressive pressure in real time because it is made of transparent materials and stimulates the cells without deforming the cell culture surface, when observed by optical microscopy. We demonstrated the validity of the fabrication process, evaluated the performance of the fabricated device, and compared the experimental results with the FEM structural analysis results. We found through operational testing that the diaphragm was deformed quickly by applying negative/positive pressure and that the diaphragm displacement became larger with increasing applied pressure. These results indicate that this device can be used to control the intensity and the cell stimulus profile by regulating the applied pressure. In all cases, the cellular deformation during compression stimulus was successfully observed in real time using an optical microscope. The device is expected to facilitate the control of stem cell differentiation and the clarification of cellular mechanoreceptor mechanisms and signal transduction pathways. PMID- 22667646 TI - A pressure gauge based on gas density measurement from analysis of the thermal noise of an atomic force microscope cantilever. AB - We describe a gas-density gauge based on the analysis of the thermally-driven fluctuations of an atomic force microscope (AFM) cantilever. The fluctuations are modeled as a ring-down of a simple harmonic oscillator, which allows fitting of the resonance frequency and damping of the cantilever, which in turn yields the gas density. The pressure is obtained from the density using the known equation of state. In the range 10-220 kPa, the pressure readings from the cantilever gauge deviate by an average of only about 5% from pressure readings on a commercial gauge. The theoretical description we use to determine the pressure from the cantilever motion is based upon the continuum hypothesis, which sets a minimum pressure for our analysis. It is anticipated that the cantilever gauge could be extended to measure lower pressures given a molecular theoretical description. Alternatively, the gauge could be calibrated for use in the non continuum range. Our measurement technique is similar to previous AFM cantilever measurements, but the analysis produces improved accuracy. PMID- 22667647 TI - Fiber-optic liquid level sensor based on coupling optical path length variation. AB - The concept for a new and simple fiber-optic liquid level sensor is presented and experimental results are shown to demonstrate the principle. The sensing principle is based on light intensity modulation when rising and falling mode of liquid level causes coupling optical path distance variation between two optical fibers. Near continuous mode of liquid level variation could be monitored with resolution as low as 1 mm can be measured in the length scale of 25 cm. PMID- 22667648 TI - A new concept in underwater high fidelity low frequency sound generation. AB - This article reports on a new type of system for high fidelity underwater sound generation (patent pending PT105474). The system includes an underwater sound actuator and the corresponding electronic driver. The sound is generated by a rigid plate that is actuated (both for positioning/dumping and excitation) using purely electromagnetic forces, thus, avoiding the use of any elastic membrane. Since there is no compressible air inside the device, which is flooded by water, the operation of this device is independent from depth, broadening its applications to any water pressure. Characterization of the frequency response, the radiation characteristics, and the dynamic range of this new device for underwater sound generation is presented. PMID- 22667649 TI - Comparison of two experimental methods for the mechanical characterization of thin or thick films from the study of micromachined circular diaphragms. AB - The purpose of this study was to compare two experimental methods and evaluate the effectiveness of a set of analytical models in order to measure the initial stress and the Young's modulus value of thin and thick film materials. Two types of experiments were performed on micromachined circular diaphragms: bulge testing and vibrometry. The range of validity and accuracy of the analytical models with respect to the vibration of the diaphragms was discussed from the finite element simulations. It was shown that the a/t ratio should be considered carefully to determine the value of the Young's modulus by vibrometry with an acceptable error. A relative error of approximately +/-10% on E was obtained for a/t <= 750. For 750 <= a/t <= 1000, the value of the dimensionless parameter k must also be considered. It has been shown that the residual stress value can be obtained with an accuracy of 10% or less, given that k > 12. As an illustration, experimental methods and models were applied to the characterization of a thick electroplated gold film and a sputter-deposited Inconel thin film. Circular structures were defined by vertical sidewalls etched on the back of a Si wafer using the deep reactive ion etching technique. In addition to analytical models, parametric finite element simulations and a design optimization technique were used to determine the material's mechanical properties. The static deflections of the diaphragms were measured as a function of the applied pressure. The resonant frequencies and mode shapes of the vibrating structures were observed under vacuum by white-light interferometric microscopy. For gold, it was found that E = (53 +/- 20) GPa and sigma(0) = (180 +/- 10) MPa. For Inconel, it was found that E = (157 +/- 14) GPa and sigma(0) = (172 +/- 5) MPa. PMID- 22667650 TI - Magnetostatic detection using magnetoresistive sensors with vertical motion flux modulation. AB - Recently, the flux modulation has been presented to deal with the 1/f noise of magnetoresistive (MR) sensors. However, the efficiency of most flux modulation schemes with simple micro- electromechanical-system (MEMS) actuators is not satisfying yet. In this paper, the vertical motion flux modulation (VMFM) is proposed to improve the modulation efficiency. In VMFM, the soft magnetic film driven by a MEMS actuator vibrates vertically above the MR sensors with a pair of flux concentrators. Consequently, the detected magnetostatic field is modulated to the higher frequency where the 1/f noise is much lower. A VMFM prototype based on AA002 (multi-layered giant magnetoresistive sensors) was fabricated and its flux modulation efficiency can reach 18.7%, which exceeds most achieved efficiency with other schemes. Also, the magnetostatic detection ability is improved to 530 pT/?Hz. PMID- 22667651 TI - A wall-free climate unit for acoustic levitators. AB - Acoustic levitation represents the physical background of trapping a sample in a standing acoustic wave with no contact to the wave generating device. For the last three decades, sample holders based on this effect have been commonly used for contact free handling of samples coupled with a number of analytical techniques. In this study, a wall-free climate unit is presented, which allows the control of the environmental conditions of suspended samples. The insulation is based on a continuous cold/hot gas flow around the sample and thus does not require any additional isolation material. This provides a direct access to the levitated sample and circumvents any influence of the climate unit material to the running analyses. PMID- 22667652 TI - An atomic beam source for fast loading of a magneto-optical trap under high vacuum. AB - We report on a directional atomic beam created using an alkali metal dispenser and a nozzle. By applying a high current (15 A) pulse to the dispenser at room temperature we can rapidly heat it to a temperature at which it starts dispensing, avoiding the need for preheating. The atomic beam produced is capable of loading 90% of a magneto-optical trap (MOT) in less than 7 s while maintaining a low vacuum pressure of <10(-11) Torr. The transverse velocity components of the atomic beam are measured to be within typical capture velocities of a rubidium MOT. Finally, we show that the atomic beam can be turned off within 1.8 s. PMID- 22667653 TI - Influence of the number of detectors by laser scattering method for estimation of particle size. AB - Effect of the number of detectors on an inversion problem of a scattering pattern by laser scattering method based on Mie scattering model has been investigated. The influence of the number of detectors is obtained by comparing a given size distribution and a calculated size distribution by computer simulation and experimental method. An observing range of scattering angles is from 0.0007 to 2.5 rad. A non-linear iteration method is used for calculating particle size distribution. The number of detectors is changed from 6 to 81 elements by the computer simulation. The algorithm of the inversion problem is applied with mean diameters of log-normal distribution in a range from 0.546 to 214 MUm at standard deviation of 0.27 and 0.68. Experimental results of certified mono-disperse polystyrene latex standards and a poly-disperse aluminum sample are obtained with 21, 41, and 81 elements detector, respectively. All tests are performed under conditions at diluted aqueous suspensions. Narrow size distribution is influenced by the number of detectors compared with wide size distribution. Not the number of physical detectors but the number of useful detectors affects the algorithm of the inversion problem. When the detector elements are over 20, the influence of the number of detectors is decreased. PMID- 22667654 TI - Micro-reactors for characterization of nanostructure-based sensors. AB - Fabrication and testing of micro-reactors for the characterization of nanosensors is presented in this work. The reactors have a small volume (100 MUl) and are equipped with gas input/output channels. They were machined from a single piece of kovar in order to avoid leaks in the system due to additional welding. The contact pins were electrically insulated from the body of the reactor using a borosilicate sealing glass and the reactor was hermetically sealed using a lid and an elastomeric o-ring. One of the advantages of the reactor lies in its simple assembly and ease of use with any vacuum/gas system, allowing the connection of more than one device. Moreover, the lid can be modified in order to fit a window for in situ optical characterization. In order to prove its versatility, carbon nanotube-based sensors were tested using this micro-reactor. The devices were fabricated by depositing carbon nanotubes over 1 MUm thick gold electrodes patterned onto Si/SiO(2) substrates. The sensors were tested using oxygen and nitrogen atmospheres, in the pressure range between 10(-5) and 10(-1) mbar. The small chamber volume allowed the measurement of fast sensor characteristic times, with the sensors showing good sensitivity towards gas and pressure as well as high reproducibility. PMID- 22667655 TI - Large-scale generic test stand for testing of multiple configurations of air filters utilizing a range of particle size distributions. AB - The Institute for Clean Energy Technology (ICET) at Mississippi State University has developed a test stand capable of lifecycle testing of high efficiency particulate air filters and other filters specified in American Society of Mechanical Engineers Code on Nuclear Air and Gas Treatment (AG-1) filters. The test stand is currently equipped to test AG-1 Section FK radial flow filters, and expansion is currently underway to increase testing capabilities for other types of AG-1 filters. The test stand is capable of producing differential pressures of 12.45 kPa (50 in. w.c.) at volumetric air flow rates up to 113.3 m(3)/min (4000 CFM). Testing is performed at elevated and ambient conditions for temperature and relative humidity. Current testing utilizes three challenge aerosols: carbon black, alumina, and Arizona road dust (A1-Ultrafine). Each aerosol has a different mass median diameter to test loading over a wide range of particles sizes. The test stand is designed to monitor and maintain relative humidity and temperature to required specifications. Instrumentation is implemented on the upstream and downstream sections of the test stand as well as on the filter housing itself. Representative data are presented herein illustrating the test stand's capabilities. Digital images of the filter pack collected during and after testing is displayed after the representative data are discussed. In conclusion, the ICET test stand with AG-1 filter testing capabilities has been developed and hurdles such as test parameter stability and design flexibility overcome. PMID- 22667656 TI - Effect of multiplicative noise on least-squares parameter estimation with applications to the atomic force microscope. AB - Measurement of the power spectral density of (stochastic) Brownian fluctuations of micro- and nano-devices is used frequently to gain insight into their mechanistic properties. Noise is always present in these measurements and can directly influence any parameter estimation obtained through a least-squares analysis. Importantly, measurements of the spectral density of stationary random signals, such as Brownian motion, inherently contain multiplicative noise. In this article, we theoretically analyze the impact of multiplicative noise on fit parameters extracted using a least-squares analysis. A general analysis is presented that is valid for any fit function with any number of fit parameters. This yields closed-form expressions for the expected value and variance in the fit parameters and provides a rigorous theoretical framework for a priori determination of the effect of measurement uncertainty. The theory is demonstrated and validated through Monte Carlo simulation of synthetic data and by comparison to power spectral density measurements of the Brownian fluctuations of an atomic force microscope cantilever - analytical formulas for the uncertainty in the fitted resonant frequency and quality factor are presented. The results of this study demonstrate that precise measurements of fit parameters in the presence of noise are inherently problematic - individual measurements of the power spectral density are capable of yielding fit parameters that are many standard deviations away from the mean, with finite probability. This is of direct relevance to a host of applications in measurement science, including those connected with the atomic force microscope. PMID- 22667657 TI - Differential membrane-based nanocalorimeter for high-resolution measurements of low-temperature specific heat. AB - A differential, membrane-based nanocalorimeter for general specific heat studies of very small samples, ranging from 0.5 mg to sub-MUg in mass, is described. The calorimeter operates over the temperature range from above room temperature down to 0.5 K. It consists of a pair of cells, each of which is a stack of heaters and thermometer in the center of a silicon nitride membrane, in total giving a background heat capacity less than 100 nJ/K at 300 K, decreasing to 10 pJ/K at 1 K. The device has several distinctive features: (i) The resistive thermometer, made of a Ge(1 - x)Au(x) alloy, displays a high dimensionless sensitivity ?dlnR/dlnT? ? 1 over the entire temperature range. (ii) The sample is placed in direct contact with the thermometer, which is allowed to self-heat. The thermometer can thus be operated at high dc current to increase the resolution. (iii) Data are acquired with a set of eight synchronized lock-in amplifiers measuring dc, 1st and 2nd harmonic signals of heaters and thermometer. This gives high resolution and allows continuous output adjustments without additional noise. (iv) Absolute accuracy is achieved via a variable-frequency-fixed-phase technique in which the measurement frequency is automatically adjusted during the measurements to account for the temperature variation of the sample heat capacity and the device thermal conductance. The performance of the calorimeter is illustrated by studying the heat capacity of a small Au sample and the specific heat of a 2.6 MUg piece of superconducting Pb in various magnetic fields. PMID- 22667658 TI - A ultra-high-vacuum wafer-fusion-bonding system. AB - The design of heterojunction devices is typically limited by material integration constraints and the energy band alignment. Wafer bonding can be used to integrate material pairs that cannot be epitaxially grown together due to large lattice mismatch. Control of the energy band alignment can be provided by formation of interface dipoles through control of the surface chemistry. We have developed an ultra-high-vacuum system for wafer-fusion-bonding semiconductors with in situ control and measurement of surface properties relevant to interface dipoles. A wafer-fusion-bonding chamber with annealing capabilities was integrated into an ultra-high-vacuum system with a sputtering chamber and an x-ray photoelectron spectroscopy system for preparing and measuring the surface chemistry of wafers prior to bonding. The design of the system along with initial results for the fusion-bonded InGaAs/Si heterojunction is presented. PMID- 22667659 TI - Testing the performance of a cryogenic visualization system on thermal counterflow by using hydrogen and deuterium solid tracers. AB - An experimental apparatus has been designed to analyze by visualization cryogenic flows of liquid (4)He and consequently address unresolved problems of quantum turbulence. The newly implemented flow visualization setup is described and its specific features discussed. Thermal counterflow experiments have been performed and the motion of solid hydrogen and deuterium tracers studied by using the particle tracking velocimetry technique in order to probe the system capabilities. It is shown that the obtained results are consistent with the two fluid model describing the behavior of superfluid (4)He. A number of technical and fundamental issues, such as particles' aggregation, role of rotating particles in counterflow and evidence of non-Gaussian distribution of tracers' velocities, are also discussed. The apparatus appears to be well-suited to the task of analyzing cryogenic flows and potentially capable of obtaining new results stimulating further understanding of the underlying physics. PMID- 22667660 TI - Versatile system for the temperature-controlled preparation of oxide crystal surfaces. AB - We present a versatile system for the preparation of oxide crystal surfaces in the ultra-high vacuum (UHV) at temperatures up to 1300 K. Thermal treatment is accomplished by direct current heating of a tantalum foil in contact with the oxide sample. The sample temperature is measured by a thermocouple at a position close to the crystal and its reading is calibrated against the surface temperature determined by a second thermocouple temporarily attached to the surface. The design of the sample holder is based on a transferable plate originally developed for a commercial UHV scanning probe microscope. The system is, however, also suitable for the use with electron spectroscopy or electron diffraction based surface analytical techniques. We present results for the high temperature preparation of CeO(2)(111) surfaces with atomically flat terraces exhibiting perfect atomic order and cleanliness as revealed by non-contact atomic force microscopy (NC-AFM) imaging. NC-AFM imaging is, furthermore, used to demonstrate the temperature-controlled aggregation of gold atoms on the CeO(2)(111) surface and their evaporation at high temperatures. PMID- 22667661 TI - Modeling technique of capacitive discharge pumping of metal vapor lasers for electrode capacitance optimization. AB - To estimate optimum gas discharge tube (GDT) electrode capacitance of metal vapor lasers (MVLs) pumped by a longitudinal capacitive discharge, we offer to use series connection of capacitors to the electrodes of a conventionally pumped GDT with inner electrodes. It has been demonstrated that the maximum output power in CuBr lasers is obtained when the capacitances of high-voltage and ground electrodes are equal. When using a model circuit an average output power reaches 12 W that suggests the possibility of generating high average output power (>10 W) in MVLs pumped using a capacitive discharge. PMID- 22667662 TI - Characterization of solid and liquid sorbent materials for biogas purification by using a new volumetric screening instrument. AB - With the increasing utilization of biogas as an energy source the need for new materials and methods to purify and clean the corresponding gas mixtures is rising. In this regard, the application of ad- or absorptive gas purification methods has increased significantly over the last years. For fast and economic evaluation of the potential of different sorbent materials, a new volumetric screening instrument has been developed. First the measuring method and the new instrument design will be described. This instrument allows ad- and absorption, as well as desorption measurements in a technically relevant, wide pressure, and temperature range. It was used for the characterization of common sorbent materials such as activated carbons and zeolite molecular sieves. Additionally, new substances like metal-organic frameworks and ionic liquids were analyzed. Thereby the sorption of CO(2), CH(4), N(2), and H(2) was measured. The obtained data allow the direct comparison of the sorption properties of the different materials, the results of which will be presented in the second part of the paper. PMID- 22667663 TI - Means to remove electrode contamination effect of Langmuir probe measurement in space. AB - Precaution to remove the serious effect of electrode contamination in Langmuir probe experiments has not been taken in many space measurements because the effect is either not understood or ignored. We stress here that one should pay extra attention to the electrode contamination effect to get accurate and reliable plasma measurements so that the long time effort for sounding rocket/satellite missions does not end in vain or becomes less fruitful. In this paper, we describe two main features of voltage-current characteristic curves associated with the contaminated Langmuir probe, which are predicted from the equivalent circuit model, which we proposed in 1970's. We then show that fast sweeping dc Langmuir probes can give reliable results in the steady state regime. The fast sweeping probe can also give reliable results in transient situations such as satellite moves through plasma bubble in the ionosphere where the electron density drastically changes. This fact was first confirmed in our laboratory experiment. PMID- 22667664 TI - Development of a novel 3-degrees of freedom flexure based positioning system. AB - Flexure mechanisms have been widely used for nanometer positioning systems. This article presents a novel conceptual design of an ultra-precision 3-degrees of freedom (XYtheta(Z)) positioning system with nanometer precision. The main purpose of this novel stage design is for the application of measurement equipment, in particular biological specimens. The stage was designed as a hollow type and with a compact size for the inverted microscope. This stage includes piezoelectric transducer actuators, double compound amplification mechanisms, moving plate, and capacitor sensors. The double compound amplification mechanism was designed using a mathematical model and analyzed by the finite element method. Since the relationship between the variables of the hinge parameters and system performances are complicated, an optimization procedure was used to obtain the optimal design parameters, which maximized the system bandwidth. Based on the solution of the optimization problem, the design of the stage and FEM simulation results are presented. Finally, the stage was manufactured and tested. PMID- 22667665 TI - Note: wearable near-infrared spectroscopy imager for haired region. AB - A wearable optical topography system was developed that is based on near-infrared spectroscopy (NIRS) for observing brain activity noninvasively including in regions covered by hair. An avalanche photo diode, high voltage dc-dc converter, and preamplifier were placed in an electrically shielded case to be safely mounted on the head. Rubber teeth and a glass rod were prepared to clear away hair and reach the scalp. These devices realized for the first time a wearable NIRS imager for any region of the cortex. The activity in the motor cortex during finger tapping was successfully observed. PMID- 22667666 TI - Note: a simple spring-pressed heat link for low temperature vacuum environment. AB - A simple spring-pressed design aimed at improving low temperature solid-solid heat link is reported. The essence of the design is to separate the contact pressure control from heat conduction. This design is especially useful for quick sample exchange in cryogen-free cryostat with demountable sample holder. PMID- 22667667 TI - Note: response characteristics of the sensor based on LaF3 thin film to different humidified gases. AB - Electromotive force (EMF) transient curves presented that the sensor showed good repeatable response in the humidity environments using ambient atmosphere as the carrier gas at different temperatures. The 90% response time and recovery time were within 40 s and 50 s, respectively. The sensor also presented stable response characteristics in 75.1% RH and 83.6% RH humidity environments using N(2), 5% O(2), and 50% O(2) as the carrier gases, respectively. The EMF always increased with the partial pressure of oxygen in certain relative humidity. However, the DeltaEMF was decreased with the increase of O(2) content in the carrier gas under the condition of the variation of relative humidity from 75.1% to 83.6%. These phenomena revealed that the sensor was sensitive to water vapor without oxygen in the sample gas and too much water vapor had adverse effect on the response to oxygen. Non-Nernst behavior of the sensor was discussed in detail. PMID- 22667668 TI - Note: innovative demodulation scheme for coherent detectors in cosmic microwave background experiments. AB - We propose an innovative demodulation scheme for coherent detectors used in cosmic microwave background polarization experiments. Removal of non-white noise, e.g., narrow-band noise, in detectors is one of the key requirements for the experiments. A combination of modulation and demodulation is used to extract polarization signals as well as to suppress such noise. Traditional demodulation, which is based on the two-point numerical differentiation, works as a first-order high pass filter for the noise. The proposed demodulation is based on the three point numerical differentiation. It works as a second-order high pass filter. By using a real detector, we confirmed significant improvements of suppression power for the narrow-band noise. We also found improvement of the noise floor. PMID- 22667669 TI - Note: how to design Gaussian filter with eccentricity and probe offset taken into account for roundness measurement of small radius. AB - A Gaussian filter is designed using circular convolution with eccentricity and probe offset taken into account for roundness measurement. It is found through analyses and experiments that the newly designed filter can perform as well as a fast Fourier Gaussian filter for high precision calibration in laboratory, and it can be better used for roundness measurement of small radius with high eccentricity and probe offset as well. PMID- 22667670 TI - Note: long range and accurate measurement of deep trench microstructures by a specialized scanning tunneling microscope. AB - A compact but practical scanning tunneling microscope (STM) with high aspect ratio and high depth capability has been specially developed. Long range scanning mechanism with tilt-adjustment stage is adopted for the purpose of adjusting the probe-sample relative angle to compensate the non-parallel effects. A periodical trench microstructure with a pitch of 10 MUm has been successfully imaged with a long scanning range up to 2.0 mm. More innovatively, a deep trench with depth and step height of 23.0 MUm has also been successfully measured, and slope angle of the sidewall can approximately achieve 67 degrees . The probe can continuously climb the high step and exploring the trench bottom without tip crashing. The new STM could perform long range measurement for the deep trench and high step surfaces without image distortion. It enables accurate measurement and quality control of periodical trench microstructures. PMID- 22667671 TI - Note: a flexible light emitting diode-based broadband transient-absorption spectrometer. AB - This Note presents a simple and flexible ns-to-ms transient absorption spectrometer based on pulsed light emitting diode (LED) technology that can be incorporated into existing ultrafast transient absorption spectrometers or operate as a stand-alone instrument with fixed-wavelength laser sources. The LED probe pulses from this instrument exhibit excellent stability (~0.5%) and are capable of producing high signal-to-noise long-time (>100 ns) transient absorption signals either in a broadband multiplexed (spanning 250 nm) or in tunable narrowband (20 ns) operation. The utility of the instrument is demonstrated by measuring the photoinduced ns-to-ms photodynamics of the red/green absorbing fourth GMP phosphodiesterase/adenylyl cyclase/FhlA domain of the NpR6012 locus of the nitrogen-fixing cyanobacterium Nostoc punctiforme. PMID- 22667672 TI - Note: measurement of the runaway electrons in the J-TEXT tokamak. AB - The runaway electrons have been measured by hard x-ray detectors and soft x-ray array in the J-TEXT tokamak. The hard x-ray radiations in the energy ranges of 0.5-5 MeV are measured by two NaI detectors. The flux of lost runaway electrons can be obtained routinely. The soft x-ray array diagnostics are used to monitor the runaway beam generated in disruptions since the soft x-ray is dominated by the interaction between runaway electrons and metallic impurities inside the plasma. With the aid of soft x-ray array, runaway electron beam has been detected directly during the formation of runaway current plateau following the disruptions. PMID- 22667673 TI - Note: emittance measurements of intense pulsed proton beam for different pulse length and repetition rate. AB - The high intensity ion source (SILHI), in operation at CEA-Saclay, has been used to produce a 90 mA pulsed proton beam with pulse length and repetition rates suitable for the European Spallation Source (ESS) linac. Typical r-r(') rms normalized emittance values smaller than 0.2pi mm mrad have been measured for operation in pulsed mode (0.01 < duty cycle < 0.15 and 1 ms < pulse duration < 10 ms) that are relevant for the design update of the Linac to be used at the ESS in Lund. PMID- 22667676 TI - Fluid structure interaction with contact surface methodology for evaluation of endovascular carotid implants for drug-resistant hypertension treatment. AB - Drug-resistant hypertensive patients may be treated by mechanical stimulation of stretch-sensitive baroreceptors located in the sinus of carotid arteries. To evaluate the efficacy of endovascular devices to stretch the carotid sinus such that the induced strain might trigger baroreceptors to increase action potential firing rate and thereby reduce systemic blood pressure, numerical simulations were conducted of devices deployed in subject-specific carotid models. Two models were chosen--a typical physiologic carotid and a diminutive atypical physiologic model representing a clinically worst case scenario--to evaluate the effects of device deployment in normal and extreme cases, respectively. Based on the anatomical dimensions of the carotids, two different device sizes were chosen out of five total device sizes available. A fluid structure interaction (FSI) simulation methodology with contact surface between the device and the arterial wall was implemented for resolving the stresses and strains induced by device deployment. Results indicate that device deployment in the carotid sinus of the physiologic model induces an increase of 2.5% and 7.5% in circumferential and longitudinal wall stretch, respectively, and a maximum of 54% increase in von Mises arterial stress at the sinus wall baroreceptor region. The second device, deployed in the diminutive carotid model, induces an increase of 6% in both circumferential and longitudinal stretch and a 50% maximum increase in von Mises stress at the sinus wall baroreceptor region. Device deployment has a minimal effect on blood-flow patterns, indicating that it does not adversely affect carotid bifurcation hemodynamics in the physiologic model. In the smaller carotid model, deployment of the device lowers wall shear stress at sinus by 16% while accelerating flow entering the external carotid artery branch. Our FSI simulations of carotid arteries with deployed device show that the device induces localized increase in wall stretch at the sinus, suggesting that this will activate baroreceptors and subsequently may control hypertension in drug resistant hypertensive patients, with no consequential deleterious effects on the carotid sinus hemodynamics. PMID- 22667677 TI - Rotational stiffness of football shoes influences talus motion during external rotation of the foot. AB - Shoe-surface interface characteristics have been implicated in the high incidence of ankle injuries suffered by athletes. Yet, the differences in rotational stiffness among shoes may also influence injury risk. It was hypothesized that shoes with different rotational stiffness will generate different patterns of ankle ligament strain. Four football shoe designs were tested and compared in terms of rotational stiffness. Twelve (six pairs) male cadaveric lower extremity limbs were externally rotated 30 deg using two selected football shoe designs, i.e., a flexible shoe and a rigid shoe. Motion capture was performed to track the movement of the talus with a reflective marker array screwed into the bone. A computational ankle model was utilized to input talus motions for the estimation of ankle ligament strains. At 30 deg of rotation, the rigid shoe generated higher ankle joint torque at 46.2 +/- 9.3 Nm than the flexible shoe at 35.4 +/- 5.7 Nm. While talus rotation was greater in the rigid shoe (15.9 +/- 1.6 deg versus 12.1 +/- 1.0 deg), the flexible shoe generated more talus eversion (5.6 +/- 1.5 deg versus 1.2+/- 0.8 deg). While these talus motions resulted in the same level of anterior deltoid ligament strain (approxiamtely 5%) between shoes, there was a significant increase of anterior tibiofibular ligament strain (4.5+/- 0.4% versus 2.3 +/- 0.3%) for the flexible versus more rigid shoe design. The flexible shoe may provide less restraint to the subtalar and transverse tarsal joints, resulting in more eversion but less axial rotation of the talus during foot/shoe rotation. The increase of strain in the anterior tibiofibular ligament may have been largely due to the increased level of talus eversion documented for the flexible shoe. There may be a direct correlation of ankle joint torque with axial talus rotation, and an inverse relationship between torque and talus eversion. The study may provide some insight into relationships between shoe design and ankle ligament strain patterns. In future studies, these data may be useful in characterizing shoe design parameters and balancing potential ankle injury risks with player performance. PMID- 22667678 TI - Effect of wall compliance and permeability on blood-flow rate in counter-current microvessels formed from anastomosis during tumor-induced angiogenesis. AB - Tumor blood-flow is inhomogeneous because of heterogeneity in tumor vasculature, vessel-wall leakiness, and compliance. Experimental studies have shown that normalization of tumor vasculature by antiangiogenic therapy can improve tumor microcirculation and enhance the delivery of therapeutic agents to tumors. To elucidate the quantitative relationship between the vessel-wall compliance and permeability and the blood-flow rate in the microvessels of the tumor tissue, the tumor tissue with the normalized vasculature, and the normal tissue, we developed a transport model to simultaneously predict the interstitial fluid pressure (IFP), interstitial fluid velocity (IFV) and the blood-flow rate in a counter current microvessel loop, which occurs from anastomosis in tumor-induced angiogenesis during tumor growth. Our model predicts that although the vessel wall leakiness greatly affects the IFP and IFV, it has a negligible effect on the intravascular driving force (pressure gradient) for both rigid and compliant vessels, and thus a negligible effect on the blood-flow rate if the vessel wall is rigid. In contrast, the wall compliance contributes moderately to the IFP and IFV, but significantly to the vessel radius and to the blood-flow rate. However, the combined effects of vessel leakiness and compliance can increase IFP, which leads to a partial collapse in the blood vessels and an increase in the flow resistance. Furthermore, our model predictions speculate a new approach for enhancing drug delivery to tumor by modulating the vessel-wall compliance in addition to reducing the vessel-wall leakiness and normalizing the vessel density. PMID- 22667679 TI - Examining differences in local collagen fiber crimp frequency throughout mechanical testing in a developmental mouse supraspinatus tendon model. AB - Crimp morphology is believed to be related to tendon mechanical behavior. While crimp has been extensively studied at slack or nondescript load conditions in tendon, few studies have examined crimp at specific, quantifiable loading conditions. Additionally, the effect of the number of cycles of preconditioning on collagen fiber crimp behavior has not been examined. Further, the dependence of collagen fiber crimp behavior on location and developmental age has not been examined in the supraspinatus tendon. Local collagen fiber crimp frequency is quantified throughout tensile mechanical testing using a flash freezing method immediately following the designated loading protocol. Samples are analyzed quantitatively using custom software and semi-quantitatively using a previously established method to validate the quantitative software. Local collagen fiber crimp frequency values are compared throughout the mechanical test to determine where collagen fiber frequency changed. Additionally, the effect of the number of preconditioning cycles is examined compared to the preload and toe-region frequencies to determine if increasing the number of preconditioning cycles affects crimp behavior. Changes in crimp frequency with age and location are also examined. Decreases in collagen fiber crimp frequency were found at the toe region at all ages. Significant differences in collagen fiber crimp frequency were found between the preload and after preconditioning points at 28 days. No changes in collagen fiber crimp frequency were found between locations or between 10 and 28 days old. Local collagen fiber crimp frequency throughout mechanical testing in a postnatal developmental mouse SST model was measured. Results confirmed that the uncrimping of collagen fibers occurs primarily in the toe region and may contribute to the tendon's nonlinear behavior. Additionally, results identified changes in collagen fiber crimp frequency with an increasing number of preconditioning cycles at 28 days, which may have implications on the measurement of mechanical properties and identifying a proper reference configuration. PMID- 22667680 TI - A detailed and validated three dimensional dynamic model of the patellofemoral joint. AB - A detailed 3D anatomical model of the patellofemoral joint was developed to study the tracking, force, contact and stability characteristics of the joint. The quadriceps was considered to include six components represented by 15 force vectors. The patellar tendon was modeled using four bundles of viscoelastic tensile elements. Each of the lateral and medial retinaculum was modeled by a three-bundle nonlinear spring. The femur and patella were considered as rigid bodies with their articular cartilage layers represented by an isotropic viscoelastic material. The geometrical and tracking data needed for model simulation, as well as validation of its results, were obtained from an in vivo experiment, involving MR imaging of a normal knee while performing isometric leg press against a constant 140 N force. The model was formulated within the framework of a rigid body spring model and solved using forth-order Runge-Kutta, for knee flexion angles between zero and 50 degrees. Results indicated a good agreement between the model predictions for patellar tracking and the experimental results with RMS deviations of about 2 mm for translations (less than 0.7 mm for patellar mediolateral shift), and 4 degrees for rotations (less than 3 degrees for patellar tilt). The contact pattern predicted by the model was also consistent with the results of the experiment and the literature. The joint contact force increased linearly with progressive knee flexion from 80 N to 210 N. The medial retinaculum experienced a peak force of 18 N at full extension that decreased with knee flexion and disappeared entirely at 20 degrees flexion. Analysis of the patellar time response to the quadriceps contraction suggested that the muscle activation most affected the patellar shift and tilt. These results are consistent with the recent observations in the literature concerning the significance of retinaculum and quadriceps in the patellar stability. PMID- 22667682 TI - Ventricle equilibrium position in healthy and normal pressure hydrocephalus brains using an analytical model. AB - The driving force that causes enlargement of the ventricles remains unclear in case of normal pressure hydrocephalus (NPH). Both healthy and NPH brain conditions are characterized by a low transparenchymal pressure drop, typically 1 mm Hg. The present paper proposes an analytical model for normal and NPH brains using Darcy's and Biot's equations and simplifying the brain geometry to a hollow sphere with an internal and external radius. Self-consistent solutions for the large deformation problem that is associated with large ventricle dilation are presented and the notion of equilibrium or stable ventricle position is highlighted for both healthy and NPH conditions. The influence of different biomechanical parameters on the stable ventricle geometry is assessed and it is shown that both CSF seepage through the ependyma and parenchymal permeability play a key role. Although very simple, the present model is able to predict the onset and development of NPH conditions as a deviation from healthy conditions. PMID- 22667681 TI - Influence of needle insertion speed on backflow for convection-enhanced delivery. AB - Fluid flow back along the outer surface of a needle (backflow) can be a significant problem during the direct infusion of drugs into brain tissues for procedures such as convection-enhanced delivery (CED). This study evaluates the effects of needle insertion speed (0.2 and 1.8 mm/s) as well as needle diameter and flow rate on the extent of backflow and local damage to surrounding tissues. Infusion experiments were conducted on a transparent tissue phantom, 0.6% (w/v) agarose hydrogel, to visualize backflow. Needle insertion experiments were also performed to evaluate local damage at the needle tip and to back out the prestress in the surrounding media for speed conditions where localized damage was not excessive. Prestress values were then used in an analytical model of backflow. At the higher insertion speed (1.8 mm/s), local insertion damage was found to be reduced and backflow was decreased. The compressive prestress at the needle-tissue interface was estimated to be approximately constant (0.812 kPa), and backflow distances were similar regardless of needle gauge (22, 26, and 32 gauge). The analytical model underestimated backflow distances at low infusion flow rates and overestimated backflow at higher flow rates. At the lower insertion speed (0.2 mm/s), significant backflow was measured. This corresponded to an observed accumulation of material at the needle tip which produced a gap between the needle and the surrounding media. Local tissue damage was also evaluated in excised rat brain tissues, and insertion tests show similar rate dependent accumulation of tissue at the needle tip at the lower insertion speed. These results indicate that local tissue damage and backflow may be avoided by using an appropriate insertion speed. PMID- 22667683 TI - A novel device to apply controlled flexion and extension to the rat knee following anterior cruciate ligament reconstruction. AB - We designed and validated a novel device for applying flexion-extension cycles to a rat knee in an in vivo model of anterior cruciate ligament reconstruction (ACL R). Our device is intended to simulate rehabilitation motion and exercise post ACL-R to optimize physical rehabilitation treatments for the improved healing of tendon graft ligament reconstructions. The device was validated for repeatability of the knee kinematic motion by measuring the force versus angular rotation response from repeated trials using cadaver rats. The average maximum force required for rotating an ACL reconstructed rat knee through 100 degrees of flexion-extension was 0.4 N with 95% variability for all trials within +/-0.1 N. PMID- 22667685 TI - Bactericidal effects of low-intensity extremely high frequency electromagnetic field: an overview with phenomenon, mechanisms, targets and consequences. AB - Low-intensity electromagnetic field (EMF) of extremely high frequencies is a widespread environmental factor. This field is used in telecommunication systems, therapeutic practices and food protection. Particularly, in medicine and food industries EMF is used for its bactericidal effects. The significant targets of cellular mechanisms for EMF effects at resonant frequencies in bacteria could be water (H(2)O), cell membrane and genome. The changes in H(2)O cluster structure and properties might be leading to increase of chemical activity or hydration of proteins and other cellular structures. These effects are likely to be specific and long-term. Moreover, cell membrane with its surface characteristics, substance transport and energy-conversing processes is also altered. Then, the genome is affected because the conformational changes in DNA and the transition of bacterial pro-phages from lysogenic to lytic state have been detected. The consequences for EMF interaction with bacteria are the changes in their sensitivity to different chemicals, including antibiotics. These effects are important to understand distinguishing role of bacteria in environment, leading to changed metabolic pathways in bacteria and their antibiotic resistance. This EMF may also affect the cell-to-cell interactions in bacterial populations, since bacteria might interact with each other through EMF of sub-extremely high frequency range. PMID- 22667684 TI - An in vitro fluid dynamic study of pediatric cannulae: the value of animal studies to predict human flow. AB - A challenge to the development of pediatric ventricular assist devices (PVADs) is the use of the aortic cannulae attached to the devices. Cannulae used for pediatric application have small diameters and large pressure drops. Furthermore, during the development of the 12cc Penn State pediatric PVAD, particle image velocimetry (PIV) illustrated that hematocrit levels, through changes in blood viscoelasticity, affected the fluid dynamics. The objective of this study is to compare the fluid dynamics of a pediatric viscoelastic blood analog and a goat viscoelastic blood analog within the PVAD aortic cannula. Two acrylic models were manufactured to model the aortic cannula (6 mm and 8 mm diameters). PIV data was collected to examine the flow at the outlet of the VAD and in the aortic cannula at heart rates of 50 and 75 beats per minute (bpm). Three planes of data were taken, one at the centerline and two 1.5 mm above and below the centerline. Three more planes of data were taken orthogonal to the original planes. While a 75 bpm heart rate was used to represent normal operating conditions, a 50 bpm heart rate represented use of the PVAD during weaning. At 75 bpm, differences were evident between the two different fluids and the two models. Separation zones developed in the plane below the centerline for the higher hematocrit pediatric blood analog. This study raises question to the usefulness of animal testing results in regard to how well they predict the outcome of pediatric patients. PMID- 22667686 TI - Theoretical insight into the structural stability of KZnB3O6 polymorphs with different BO(x) polyhedral networks. AB - In general, the presence of shared edges of polyhedra for high-valence low coordinated small cations is rarely seen except under extreme conditions such as high pressure. However, the ambient-pressure synthesis of KZnB(3)O(6) built of edge-sharing BO(4) tetrahedra is contrary to this. By investigating the molecular dynamics, lattice dynamics, and electronic properties via density functional theory, we studied the origin of the phase stability of the edge-sharing (es) and "corner-sharing (cs)" KZnB(3)O(6). Lattice dynamics results show that there are no phonon anomalies that could lead to the instability of es-KZnB(3)O(6), which is consistent with molecular dynamics analysis. For "cs-KZnB(3)O(6)", a soft mode at the G point in the phonon dispersion is identified that reflects the dynamic instability with respect to small distortions. Eigenvector analysis of the soft mode of "cs-KZnB(3)O(6)" indicates that the instability comes from the linkage of ZnO(5) polyhedra rather than BO(x) polyhedra. Electronic property calculation indicates that the edge-sharing BO(4) polyhedra connected by the longest B-O sigma bonds provide a solid framework for es-KZnB(3)O(6). In the case of "cs KZnB(3)O(6)", the overlong Zn-O bond possesses the smallest covalent nature and the least orbital overlap among the bonds in a ZnO(5) polyhedron, and these two features of the electronic structure reduce the stability of "cs-KZnB(3)O(6)" compared to es-KZnB(3)O(6). The electronic property calculation further confirms the results obtained from lattice dynamics analysis. PMID- 22667688 TI - Palladium-catalyzed conjugate addition of terminal alkynes to enones. AB - A practical protocol for the hydroalkynylation of enones using Pd catalysis is reported. The reaction proceeds efficiently with a variety of alkynes as well as with several cyclic and acyclic enones, providing synthetically relevant beta alkynyl ketones in good to excellent yields. PMID- 22667687 TI - Fully functionalized small-molecule probes for integrated phenotypic screening and target identification. AB - Phenotypic screening offers a powerful approach to identify small molecules that perturb complex biological processes in cells and organisms. The tendency of small molecules, however, to interact with multiple protein targets, often with moderate to weak affinities, along with the lack of straightforward technologies to characterize these interactions in living systems, has hindered efforts to understand the mechanistic basis for pharmacological activity. Here we address this challenge by creating a fully functionalized small-molecule library whose membership is endowed with: (1) one or more diversity elements to promote interactions with different protein targets in cells, (2) a photoreactive group for UV light-induced covalent cross-linking to interacting proteins, and (3) an alkyne handle for reporter tag conjugation to visualize and identify cross-linked proteins. A library member was found to inhibit cancer cell proliferation selectively under nutrient-limiting (low glucose) conditions. Quantitative chemoproteomics identified MT-ND1, an integral membrane subunit of the ~1 MDa NADH:ubiquinone oxidoreductase (complex 1) involved in oxidative phosphorylation, as a specific target of the active probe. We further demonstrated that the active probe inhibits complex 1 activity in vitro (IC(50) = 720 nM), an effect that is known to induce cell death in low-glucose conditions. Based on this proof of principle study, we anticipate that the generation and integration of fully functionalized compound libraries into phenotypic screening programs should facilitate the discovery of bioactive probes that are amenable to accelerated target identification and mechanistic characterization using advanced chemoproteomic technologies. PMID- 22667689 TI - Cyclization of 1,6-enynes catalyzed by gold nanoparticles supported on TiO2: significant changes in selectivity and mechanism, as compared to homogeneous Au catalysis. AB - Gold nanoparticles supported on TiO(2) (1.2 mol %) catalyze, for the first time under heterogeneous conditions, the cycloisomerization of a series of 1,6-enynes in high yields. In several cases, the product selectivity differs significantly as compared to homogeneous Au(I)-catalysis. Based on product analysis and stereoisotopic studies it is proposed that the major or exclusive pathway involves a 5-exo cyclization mode to form stereoselectively gold cyclopropyl carbenes that undergo a single cleavage pathway, in contrast to homogeneous Au catalysis where the double cleavage pathway operates substantially. PMID- 22667690 TI - Life cycle Greenhouse gas emissions of current Oil Sands Technologies: surface mining and in situ applications. AB - Life cycle greenhouse gas (GHG) emissions associated with two major recovery and extraction processes currently utilized in Alberta's oil sands, surface mining and in situ, are quantified. Process modules are developed and integrated into a life cycle model-GHOST (GreenHouse gas emissions of current Oil Sands Technologies) developed in prior work. Recovery and extraction of bitumen through surface mining and in situ processes result in 3-9 and 9-16 g CO(2)eq/MJ bitumen, respectively; upgrading emissions are an additional 6-17 g CO(2)eq/MJ synthetic crude oil (SCO) (all results are on a HHV basis). Although a high degree of variability exists in well-to-wheel emissions due to differences in technologies employed, operating conditions, and product characteristics, the surface mining dilbit and the in situ SCO pathways have the lowest and highest emissions, 88 and 120 g CO(2)eq/MJ reformulated gasoline. Through the use of improved data obtained from operating oil sands projects, we present ranges of emissions that overlap with emissions in literature for conventional crude oil. An increased focus is recommended in policy discussions on understanding interproject variability of emissions of both oil sands and conventional crudes, as this has not been adequately represented in previous studies. PMID- 22667691 TI - Controlling the stability and size of double-emulsion-templated poly(lactic-co glycolic) acid microcapsules. AB - The stability and size of poly(lactic-co-glycolic)acid (PLGA)-containing double emulsions and the resulting PLGA microcapsules are controlled by varying the composition of highly monodisperse water-in-oil-in-water (W/O/W) double emulsions. We propose that the basic inner phase of W/O/W double emulsions catalyzes the hydrolysis of PLGA and the ionization of carboxylic acid end groups, which enhances the surface activity of PLGA and facilitates the stabilization of the double emulsions. The size of PLGA-containing double emulsions and that of resulting microcapsules can be readily tuned by osmotic annealing, which depends on the concentration ratio of a solute in the inner and outer phases of double emulsions. The internal volume of PLGA microcapsules can be changed by more than 3 orders of magnitude using this method. This approach also overcomes the difficulty in generating monodisperse double emulsions and microcapsules over a wide range of dimensions using a single microfluidic device. The osmotic annealing method can also be used to concentrate encapsulated species such as colloidal suspensions and biomacromolecules. PMID- 22667692 TI - A propensity scale for type II polyproline helices (PPII): aromatic amino acids in proline-rich sequences strongly disfavor PPII due to proline-aromatic interactions. AB - Type II polyproline helices (PPII) are a fundamental secondary structure of proteins, common in globular and nonglobular regions and important in cellular signaling. We developed a propensity scale for PPII using a host-guest system with sequence Ac-GPPXPPGY-NH(2), where X represents any amino acid. We found that proline has the highest PPII propensity, but most other amino acids display significant PPII propensities. The PPII propensity of leucine was the highest of all propensities of non-proline residues. Alanine and residues with linear side chains displayed the next highest PPII propensities. Three classes of residues displayed lower PPII propensities: beta-branched amino acids (Thr, Val, and Ile), short amino acids with polar side chains (Asn, protonated Asp, Ser, Thr, and Cys), and aromatic amino acids (Phe, Tyr, and Trp). tert-Leucine particularly disfavored PPII. The basis of the low PPII propensities of aromatic amino acids in this context was significant cis-trans isomerism, with proline-rich peptides containing aromatic residues exhibiting 45-60% cis amide bonds, due to Pro-cis Pro-aromatic and aromatic-cis-Pro amide bonds. PMID- 22667695 TI - A mobile phone short message service improves perceived control of asthma: a randomized controlled trial. AB - OBJECTIVE: Mobile phone short message service (SMS) has been suggested as a potentially powerful tool to improve asthma outcomes, and it can overcome external barriers such as time and distance to participate education programs. We wanted to know whether SMS can help to overcome intrinsic barriers such as perceived control of asthma (PCA). SUBJECTS AND METHODS: One hundred fifty outpatients with asthma were randomly assigned to the control, traditional, and SMS groups. Patients in all groups received verbal education based on the Global Initiative for Asthma, and patients in the traditional group received additional individualized asthma action plan for self-management with peak expiratory flow monitoring and recording asthma diary, while patients in the SMS group received additional daily SMS reminders on their mobile phone. The six-item PCA Questionnaire (PCAQ-6), Standard Asthma-Specific Quality of Life [AQLQ(S)], spirometry, blood and induced sputum cell count, follow-up compliance rate, medicine compliance rate, and emergency department (ED) visits data were collected at the initial visit and at 12 weeks. RESULTS: In total, 71 participants completed the trial for analysis. Patients' PCAQ-6 score was significantly increased in the SMS and traditional groups (p<0.001) after 12 weeks, and the change of patients' PCAQ-6 score in the SMS group was higher than in the traditional group (p=0.018). Patients in the SMS group had the highest AQLQ(S) score and follow-up rate after 12 weeks. The change in PCAQ-6 score was associated with change in AQLQ(S) score (r=0.442). Patients in all groups had better forced expiratory volume in 1 s (FEV1%) and fewer ED visits after 12 weeks, but no significant differences were found among the three groups in the changes of FEV1% and blood and induced sputum eosinophil counts and neutrophil counts. CONCLUSIONS: SMS can improve PCA, and it has a greater advantage in improving follow-up rate and asthma-specific quality of life than traditional programs. PMID- 22667696 TI - International telepharmacy education: another venue to improve cancer care in the developing world. AB - OBJECTIVE: In developed countries, pharmacists play a crucial role in designing and implementing cancer treatments as part of a multidisciplinary oncology team. However, developing countries have a shortage of pharmacists, and their role is generally limited to dispensing and selling drugs. The aim of this study was to investigate the feasibility of providing clinical pharmacy educational activities via international teleconferencing to improve cancer care in developing countries. MATERIALS AND METHODS: Meticulous preparation and intense promotion of the workshop were done in Egypt before the telepharmacy conferences began. Multiple connectivity tests were performed to resolve technical problems. Nine telepharmacy conferences were delivered during 3-h sessions that were held on three consecutive days. Talks were subsequently made available via Web streaming. Attendees were requested to complete a survey to measure their satisfaction with the sessions. RESULTS: The teleconference was attended by a total of 345 persons, and it was subsequently reviewed online via 456 log-in sessions from 10 countries. Technical issues (e.g., poor auditory quality) were resolved on the first day of the event. The rate of attendees' responses on the survey was 30.1%, and satisfaction with the event was generally good. CONCLUSIONS: Telecommunication is a relatively inexpensive approach that may improve pharmacy practices, especially those used to treat patients with cancer in developing countries. Special attention to patient-based telepharmacy education, including the use of cost-effective technology, should be considered. PMID- 22667698 TI - Biotechnica. PMID- 22667697 TI - Health care costs of physical inactivity in Canadian adults. AB - The purpose of this study was to provide a contemporary estimate of the health care cost of physical inactivity in Canadian adults. The health care cost was estimated using a prevalence-based approach. The estimated direct, indirect, and total health care costs of physical inactivity in Canada in 2009 were $2.4 billion, $4.3 billion, and $6.8 billion, respectively. These values represented 3.8%, 3.6%, and 3.7% of the overall health care costs. PMID- 22667699 TI - Get a first look at the last word in materials chemistry. PMID- 22667700 TI - Turner designs. PMID- 22667702 TI - At last! The piece that helps you solve the health and safety puzzle for everyone working with chemicals. PMID- 22667703 TI - Questioning "incremental science". PMID- 22667704 TI - Benign by design: alternative synthetic design for pollution prevention. PMID- 22667706 TI - Atmospheric partitioning. PMID- 22667705 TI - Dioxin-free paper. PMID- 22667708 TI - MIMS configurations. PMID- 22667707 TI - Methane production. PMID- 22667709 TI - Benzene in sediments. PMID- 22667711 TI - Sediment bioassay. PMID- 22667710 TI - Kinetic parameters. PMID- 22667712 TI - Dioxins and furans. PMID- 22667713 TI - A watershed approach to mercury transport. PMID- 22667714 TI - PAH degradation. PMID- 22667715 TI - Societal decision making. PMID- 22667716 TI - Environmental quality. PMID- 22667717 TI - Ecological risk tools. PMID- 22667718 TI - Quality guidelines. PMID- 22667720 TI - Eighth international congress of pesticide chemistry: options 2000. PMID- 22667719 TI - Wetlands treatment. PMID- 22667722 TI - Sludge and PAHs. PMID- 22667721 TI - Colloid generation measurements. PMID- 22667723 TI - Sludge and PCBs. PMID- 22667725 TI - RCRA to be streamlined. PMID- 22667724 TI - EPA sets new guidelines for environmental projects. PMID- 22667726 TI - ORD reorganization completes first phase. PMID- 22667727 TI - Radiation and public perception. PMID- 22667728 TI - Public hearings to be held on "brownfields". PMID- 22667729 TI - Court rules against ethanol mandate. PMID- 22667730 TI - Common toxic products exempt from RCRA. PMID- 22667732 TI - EPA research faces major cuts. PMID- 22667731 TI - SAB advisory panel rejects dioxin risk characterization. PMID- 22667733 TI - Wetlands regulations need overhaul, says NRC report. PMID- 22667735 TI - Integrating environmental databases. PMID- 22667734 TI - MTBE detected in survey of urban groundwater. PMID- 22667736 TI - States turning to voluntary programs to speed cleanups. PMID- 22667738 TI - Low-level radioactive waste site receives go-ahead. PMID- 22667739 TI - Browner pledges to visit "environmental justice" sites. PMID- 22667737 TI - Clinton proposes to cut environmental health, research programs. PMID- 22667740 TI - Study encourages firms to find hidden environmental costs. PMID- 22667742 TI - Sometimes, getting ahead means taking. PMID- 22667743 TI - A status report on field-portable immunoassay. PMID- 22667744 TI - Phytoremediation of organic and nutrient contaminants. PMID- 22667746 TI - Through a special arrangement with. PMID- 22667745 TI - Ranking pesticides by environmental impact. PMID- 22667747 TI - Great research is surfacing... PMID- 22667748 TI - Analytical products. PMID- 22667749 TI - Discover chemistry from Japan. PMID- 22667751 TI - ACS Career Services. PMID- 22667752 TI - Classified section. PMID- 22667755 TI - Environment science & technology fax express. PMID- 22667754 TI - Professional comicronnsultauantaus services directory. PMID- 22667756 TI - Rhodium-catalyzed intramolecular formation of N-sulfamoyl 2,3-aziridino-gamma lactones and their use for the enantiospecific synthesis of alpha,beta-diamino acid derivatives. AB - 4-Hydroxymethylbutenolide 4 was transformed into its sulfamoyl derivative 5, which upon treatment with iodosobenzene diacetate and magnesium oxide in the presence of a rhodium catalyst afforded the product of intramolecular aziridination 6. Reaction of 6 with primary or secondary amines in DMA led to regioselective opening of the aziridine ring at C2 to give the corresponding bicyclic derivatives 7a-7g in good to excellent yields. Methanolysis of the lactone ring of the N-benzyl-N-methyl derivative 7c followed by protection of the resulting secondary hydroxy group and treatment of the product with Boc anhydride provided the activated cyclic sulfamates 13 and 14. The latter then reacted with a second nucleophile (azide or thiophenol) to give the corresponding difunctionalized alpha,beta-diamino methyl esters 15-18, 20. PMID- 22667757 TI - Long-term improvements in quality of life after functional endoscopic sinus surgery for adolescents with chronic rhinosinusitis. AB - CONCLUSIONS: The long-term quality of life of adolescents with chronic rhinosinusitis improved significantly after functional endoscopic sinus surgery (FESS), and endoscopic sinus surgery showed certain benefits for adolescent patients. The selection of appropriate patients may further improve the surgical outcomes and quality of life. OBJECTIVE: To analyze the long-term quality of life in adolescents (12-18 years) with chronic rhinosinusitis after endoscopic sinus surgery, and to evaluate the value of endoscopic sinus surgery in adolescent patients. METHODS: From 2003 to 2008, 729 adolescents with chronic sinusitis underwent endoscopic sinus surgery in our department; 270 of these patients were included in the study. Their quality of life was assessed before and within 3-8 years after the surgery using the SNOT-20 scale and was compared with that of healthy individuals of the same age. RESULTS: The SNOT-20-based assessment showed that the overall quality of life differed significantly before and after surgery (p = 0.000) and that some symptoms (dizziness, sense of facial oppression, sleep difficulty, embarrassment, and fatigue) had no significant differences before and after surgery (p > 0.05). Preoperative and postoperative symptoms (dizziness, sense of facial oppression, sleep difficulty, embarrassment, and fatigue) showed no significant differences between the healthy population and treated patients (p > 0.05). PMID- 22667759 TI - Identification of an unfolding intermediate for a DNA lesion bypass polymerase. AB - Sulfolobus solfataricus DNA Polymerase IV (Dpo4), a prototype Y-family DNA polymerase, has been well characterized biochemically and biophysically at 37 degrees C or lower temperatures. However, the physiological temperature of the hyperthermophile S. solfataricus is approximately 80 degrees C. With such a large discrepancy in temperature, the in vivo relevance of these in vitro studies of Dpo4 has been questioned. Here, we employed circular dichroism spectroscopy and fluorescence-based thermal scanning to investigate the secondary structural changes of Dpo4 over a temperature range from 26 to 119 degrees C. Dpo4 was shown to display a high melting temperature characteristic of hyperthermophiles. Unexpectedly, the Little Finger domain of Dpo4, which is only found in the Y family DNA polymerases, was shown to be more thermostable than the polymerase core. More interestingly, Dpo4 exhibited a three-state cooperative unfolding profile with an unfolding intermediate. The linker region between the Little Finger and Thumb domains of Dpo4 was found to be a source of structural instability. Through site-directed mutagenesis, the interactions between the residues in the linker region and the Palm domain were identified to play a critical role in the formation of the unfolding intermediate. Notably, the secondary structure of Dpo4 was not altered when the temperature was increased from 26 to 87.5 degrees C. Thus, in addition to providing structural insights into the thermal stability and an unfolding intermediate of Dpo4, our work also validated the relevance of the in vitro studies of Dpo4 performed at temperatures significantly lower than 80 degrees C. PMID- 22667760 TI - Polo-like kinases in AML. AB - New therapies targeting critical elements of the cell cycle open novel and attractive avenues for the treatment of cancer patients. At present, the number of clinical trials that are registered with the European Organization for Research and Treatment of Cancer (EORTC) and with the US National Cancer Institute, which investigate the efficacy of Polo-like kinase 1 (Plk1) inhibitors against solid tumors and different types of leukemia is growing. Plks are important regulators of mitotic progression. Plk1, the best characterized mammalian Plk, has become an attractive target for cancer drug development, because most types of cancer appear to be addicted to the non-oncogene Plk1. Here, the authors discuss the role of Plk1 and the potential tumor suppressor gene Plk2 in acute myeloid leukemia (AML). PMID- 22667761 TI - Novel chemical route to prepare a new polymer blend gate dielectric for flexible low-voltage organic thin-film transistor. AB - An organic-organic blend thin film has been synthesized through the solution deposition of a triblock copolymer (Pluronic P123, EO20-PO70-EO20) and polystyrene (PS), which is called P123-PS for the blend film whose precursor solution was obtained with organic additives. In addition to having excellent insulating properties, these materials have satisfied other stringent requirements for an optimal flexible device: low-temperature fabrication, nontoxic, surface free of pinhole defect, compatibility with organic semiconductors, and mechanical flexibility. Atomic force microscope measurements revealed that the optimized P123-PS blend film was uniform, crack-free, and highly resistant to moisture absorption on polyimide (PI) substrate. The film was well-adhered to the flexible Au/Cr/PI substrate for device application as a stable insulator, which was likely due to the strong molecular assembly that includes both hydrophilic and hydrophobic effects from the high molecular weights. The contact angle measurements for the P123-PS surface indicated that the system had a good hydrophobic surface with a total surface free energy of approximately 19.6 mJ m(-2). The dielectric properties of P123-PS were characterized in a cross-linked metal-insulator-metal structured device on the PI substrate by leakage current, capacitance, and dielectric constant measurements. The P123-PS film showed an average low leakage current density value of approximately 10(-10) A cm(-2) at 5-10 MV cm(-1) and large capacitance of 88.2 nF cm(-2) at 1 MHz, and the calculated dielectric constant was 2.7. In addition, we demonstrated an organic thin-film transistor (OTFT) device on a flexible PI substrate using the P123-PS as the gate dielectric layer and pentacene as the channel layer. The OTFT showed good saturation mobility (0.16 cm(2) V(-1) s(-1)) and an on-to-off current ratio of 5 * 10(5). The OTFT should operate under bending conditions; therefore flexibility tests for two types of bending modes (tensile and compressive) were also performed successfully. PMID- 22667762 TI - Cochlear implantation and hearing preservation: Results in 21 consecutively operated patients using the round window approach. AB - CONCLUSION: Prevalent hearing conservation may be achieved after round window (RW) cochlear implantation using soft and flexible electrode arrays if variations of RW anatomy, topography, and facial nerve position are considered. The most favorable electrode insertion depth remains to be established. OBJECTIVES: We assessed the incidence of cochlear function after cochlear implant (CI) electrode insertion through the RW in our first 21 consecutively operated patients aimed at hearing conservation. METHODS: Eleven patients had a preoperative low frequency hearing suitable for electro-acoustic stimulation. Hearing was preserved in an additional nine patients at their request with the intention to use full frequency CI stimulation. Anatomic variations of the RW were carefully considered using our temporal bone collection of micro-dissected ears. Electrode extension was assessed on X-ray by measuring the insertion angle of the first electrode and intra-cochlear length and correlated with audiometric data. RESULTS: There was no incidence of total loss of residual hearing in any of the patients. A slight deterioration of low frequency thresholds occurred in some patients. Mean hearing loss at 125-500 Hz was 14.4 dB at 1 month following surgery and 15.6 dB after 1 year. Insertion angle (300-540 degrees ) and depth (17.5-28.5 mm) were not statistically correlated to hearing loss. PMID- 22667763 TI - Reaction of nerve agents with phosphate buffer at pH 7. AB - Chemical weapon nerve agents, including isopropyl methylphosphonofluoridate (GB or Sarin), pinacolyl methylphosphonofluoridate (GD or Soman), and S-(2 diisopropylaminoethyl) O-ethyl methylphosphonothioate (VX), are slow to react in aqueous solutions at midrange pH levels. The nerve agent reactivity increases in phosphate buffer at pH 7, relative to distilled water or acetate buffer. Reactions were studied using (31)P NMR. Phosphate causes faster reaction to the corresponding alkyl methylphosphonic acids, and produces a mixed phosphate/phosphonate compound as an intermediate reaction product. GB has the fastest reaction rate, with a bimolecular rate constant of 4.6 * 10(-3) M(-1)s( 1)[PO(4)(3-)]. The molar product branching ratio of GB acid to the pyro product (isopropyl methylphosphonate phosphate anhydride) is 1:1.4, independent of phosphate concentration, and the pyro product continues to react much slower to form GB acid. The pyro product has two doublets in the (31)P NMR spectrum. The rate of reaction for GD is slower than GB, with a rate constant of 1.26 * 10(-3) M(-1)s(-1) [PO(4)(3-)]. The rate for VX is considerably slower, with a rate constant of 1.39 * 10(-5) M(-1)s(-1) [PO(4)(3-)], about 2 orders of magnitude slower than the rate for GD. The rate constant of the reaction of GD with pyrophosphate at pH 8 is 2.04 * 10(-3) min(-1) at a concentration of 0.0145 M. The rate of reaction for diisopropyl fluorophosphate is 2.84 * 10(-3) min(-1) at a concentration of 0.153 M phosphate, a factor of 4 slower than GD and a factor of 15 slower than GB, and there is no detectable pyro product. The half-lives of secondary reaction of the GB pyro product in 0.153 and 0.046 M solution of phosphate are 23.8 and 28.0 h, respectively, which indicates little or no dependence on phosphate. PMID- 22667764 TI - Association of angiotensin I converting enzyme polymorphism as genetic risk factor in benign prostatic hyperplasia and prostate cancer. AB - INTRODUCTION: Angiotensin I converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism is one of the genetic factors found to be related with prostate cancer (PC). We investigated the association between grade and stage of disease, age of diagnosis, vascular or perineural invasion, prediagnostic plasma prostate specific antigen (PSA) levels, and PC risk with I/D polymorphism of the ACE gene. MATERIALS AND METHODS: We recruited 206 subjects in this study, including 95 patients with PC and 111 patients with benign prostatic hyperplasia. RESULTS: The odds ratio between II and DD polymorphisms (reference) was 1.38. It means that the presence of the II polymorphism increased the risk of cancer more than 38% compared with DD polymorphism although still it was not statistically significant. The mean of total PSA in the patients with the II genotype was 20 ng/L more than that in those who had DD polymorphism. The odds ratio (OR) between the D allele and PC development was 1.16, indicating that this allele increased the risk of cancer about 16%. CONCLUSION: We found no association between the ACE polymorphism and cancer risk, overall or by grade, stage, or age of diagnosis. The difference in results for ACE polymorphisms between studies may be minimized by using larger study groups. PMID- 22667765 TI - Distribution of antigen presenting cells in the human cornea: correlation of in vivo confocal microscopy and immunohistochemistry in different pathologic entities. AB - PURPOSE: The purpose of this study was to determine the quantity and distribution of antigen presenting cells (APC) in various inflammatory and non-inflammatory corneal diseases, comparing in vivo confocal microscopy (IVCM) and immunohistochemistry. MATERIAL AND METHODS: Corneae of 41 eyes, composed of group 1 (status post herpes-keratitis), group 2 (keratoconus) and group 3 (graft rejection after keratoplasty) were investigated. IVCM was used preoperatively to assess the distribution and density of dendritic cells in the corneal center versus the paracentral area. Afterwards, all patients underwent penetrating keratoplasty. The host corneas were analyzed by immunohistochemistry for antigen presenting cell distribution, density and characterization by using specific markers for CD207/Langerin, CD209/DC-SIGN and HLA-DR. The IVCM findings were compared with immunohistochemistry results in the corneal epithelium. RESULTS: Cells with branching dendritic morphology were visualized by IVCM mainly in the basal epithelial layer and subepithelial nerve plexus of the central and paracentral cornea. The density of APC in IVCM decreased in all groups towards the central part of the cornea. The highest gradient was observed in group 2, followed by groups 1 and 3. The corneal paracenter showed similiar distribution of APC in group 1 and 2 (76.7 cells/mm(2) and 74.4 cells/mm(2)). The highest density of central APC was observed in group 1 (53.76 cells/mm(2)), followed by group 3 (27.0 cells/mm(2)) and group 2 (24.2 cells/mm(2)). In immunohistochemistry positive stained, APC were distributed similarly to IVCM but with a higher density (p < 0.05). CONCLUSION: Distribution, density and stage of maturation of corneal epithelial APCs can be evaluated on morphological basis by IVCM. However, the corneal APCs density was about three-fold lower compared to immunohistochemistry findings. PMID- 22667805 TI - Do PCL-R scores from state or defense experts best predict future misconduct among civilly committed sex offenders? AB - In a recent study of sex offender civil commitment proceedings, Murrie et al. (Psychol Public Policy Law 15:19-53, 2009) found that state-retained experts consistently assigned higher PCL-R total scores than defense-retained experts for the same offenders (Cohen's d > .83). This finding raises an important question about the validity of these discrepant scores: Which type of score, state or defense evaluator, provides the most useful information about risk? We examined the ability of PCL-R total scores from state and defense evaluators to predict future misconduct among civilly committed sex offenders (N = 38). For comparison, we also examined predictive validity when two state experts evaluated the same offender (N = 32). Agreement between evaluators was low for cases with opposing experts (ICCA,1 = .43 to .52) and for cases with two state experts (ICCA,1 = .40). Nevertheless, scores from state and defense experts demonstrated similar levels of predictive validity (AUC values in the .70 range), although scores from different types of state evaluators (corrections-contracted vs. prosecution retained) did not. The finding of mean differences between opposing evaluator scores, but similar levels of predictive validity, suggests that scores from opposing experts in SVP cases may need to be interpreted differently depending on who assigned them. Findings have important implications for understanding how rater disagreement may relate to predictive validity. PMID- 22667806 TI - The impact of mental health services on arrests of offenders with a serious mental illness. AB - This study examines the impact of mental health services on arrests of offenders with a serious mental Illness (SMI) by assessing changes in associations between receipt of outpatient and emergency room/inpatient services and arrests one, two, and three quarters later. A variety of data sets were used for identifying 3,769 offenders who were in the Pinellas County Florida jail between 7/1/2003 and 6/30/ 2004, and 7,755 offenders who were in the Harris County Texas jail between 10/1/2005 and 9/30/2006. Arrests, out-patient and emergency room/inpatient services were assigned to one of 16 ninety-day periods between 7/1/2002 and 6/10/2006 in Pinellas County and one of 12 such periods between 10/1/2004 and 9/15/2007 in Harris County. Generalized estimating equations were used. Covariates were age, gender, race, diagnosis, and homelessness. The results were also adjusted for exposure to arrests. In Pinellas County, outpatient services significantly reduced the risks of arrests 1 quarter later by 17% (odds ratio [OR] = 0.83, 95% confidence interval [CI]: 0.78-0.87, p < .001), two quarters later by 11% (OR = 0.89, 95% CI: 0.84-0.94, p < .001), and three quarters later by 9% (OR = 0.91, 95% CI: 0.86-0.96, p = .001). In Harris County, these services reduced the risk of arrest 1 quarter later by 5% (OR = 0.95, 95% CI: 0.91-0.99, p = .028), but not two and three quarters later. In Pinellas County, ER/inpatient services increased the risk of arrests by 22% (OR = 1.23, 95% CI: 1.15-1.30, p < .001), 8% (OR = 1.08, 95% CI: 1.02-1.15, p = .010) and 11% (OR = 1.11, 95% CI: 1.02-1.16, p = .001) one, two, and three quarters later. In Harris County, these services increased the risk of arrest only 1 quarter later (OR = 1.16, 95% CI: 1.11-1.22, p < .001). Results suggest that service receipt and its timing may have had some impact on the arrests of adults with a SMI and criminal justice involvement. PMID- 22667807 TI - The effect of listenability factors on the comprehension of police cautions. AB - We examined the extent to which modifying a police caution using three listenability factors (Instructions, Listing, and Explanations) improved comprehension. A 2 (Instructions vs. No Instructions) * 2 (Listing vs. No Listing) * 2 (Explanations vs. No Explanations) between-participants design was used. Participants (N = 160) were presented verbally with one of eight cautions and asked to record their understanding of the legal rights contained in the caution. Results showed a main effect of Explanations, thus suggesting that repeating the information contained in the caution in different terms increased comprehension. Partial support was also found for the hypothesized additive interactions of modifications, as the caution containing all three modifications resulted in the highest level of comprehension. The implications of these findings for the comprehension of police cautions, and verbally delivered information in general, are discussed. PMID- 22667808 TI - An explanation for camera perspective bias in voluntariness judgment for video recorded confession: Suggestion of cognitive frame. AB - Three experiments were conducted to test the hypothesis that difference in voluntariness judgment for a custodial confession filmed in different camera focuses ("camera perspective bias") could occur because a particular camera focus conveys a suggestion of a particular cognitive frame. In Experiment 1, 146 juror eligible adults in Korea showed a camera perspective bias in voluntariness judgment with a simulated confession filmed with two cameras of different focuses, one on the suspect and the other on the detective. In Experiment 2, the same bias in voluntariness judgment emerged without cameras when the participants were cognitively framed, prior to listening to the audio track of the videos used in Experiment 1, by instructions to make either a voluntariness judgment for a confession or a coerciveness judgment for an interrogation. In Experiment 3, the camera perspective bias in voluntariness judgment disappeared when the participants viewing the video focused on the suspect were initially framed to make coerciveness judgment for the interrogation and the participants viewing the video focused on the detective were initially framed to make voluntariness judgment for the confession. The results in combination indicated that a particular camera focus may convey a suggestion of a particular cognitive frame in which a video-recorded confession/interrogation is initially represented. Some forensic and policy implications were discussed. PMID- 22667809 TI - Assessing children's competency to take the oath in court: The influence of question type on children's accuracy. AB - This study examined children's accuracy in response to truth-lie competency questions asked in court. The participants included 164 child witnesses in criminal child sexual abuse cases tried in Los Angeles County over a 5-year period (1997-2001) and 154 child witnesses quoted in the U.S. state and federal appellate cases over a 35-year period (1974-2008). The results revealed that judges virtually never found children incompetent to testify, but children exhibited substantial variability in their performance based on question-type. Definition questions, about the meaning of the truth and lies, were the most difficult largely due to errors in response to "Do you know" questions. Questions about the consequences of lying were more difficult than questions evaluating the morality of lying. Children exhibited high rates of error in response to questions about whether they had ever told a lie. Attorneys rarely asked children hypothetical questions in a form that has been found to facilitate performance. Defense attorneys asked a higher proportion of the more difficult question types than prosecutors. The findings suggest that children's truth-lie competency is underestimated by courtroom questioning and support growing doubts about the utility of the competency requirements. PMID- 22667810 TI - The effect of post-identification feedback, delay, and suspicion on accurate eyewitnesses. AB - We examined whether post-identification feedback and suspicion affect accurate eyewitnesses. Participants viewed a video event and then made a lineup decision from a target-present photo lineup. Regardless of accuracy, the experimenter either, informed participants that they made a correct lineup decision or gave no information regarding their lineup decision. Immediately following the lineup decision or after a 1-week delay, a second experimenter gave some of the participants who received confirming feedback reason to be suspicious of the confirming feedback. Following immediately after the confirming feedback, accurate witnesses did not demonstrate certainty inflation. However, after a delay accurate witnesses did demonstrate certainty inflation typically associated with confirming feedback. The suspicion manipulation only affected participants' certainty when the confirming feedback created certainty inflation. The results lend support to the accessibility interpretation of the post-identification feedback effect and the erasure interpretation of the suspicion effect. PMID- 22667811 TI - The self-regulation model of sexual offending: Relationship to risk and need. AB - In the present study, we evaluated the validity and utility of the self regulation model in a sample of 275 adult male sexual offenders treated within the Correctional Service of Canada (CSC). Individuals following different self regulation pathways, as delineated in the SRM, were compared on offence characteristics, static and dynamic risk measures, and various treatment targets. Multivariate analyses revealed that, in general, offenders guided by approach motivated goals exhibited more problematic offence characteristics as well as greater risk and treatment need than individuals guided by inhibitory goals. However, several other important distinctions were noted across offenders with different goals and strategies toward offending. These findings highlight the main importance of utilizing a comprehensive and multidimensional offence process model that emphasizes multiple routes to offending in sexual offender treatment. Implications of these findings for the effective assessment and rehabilitation of sexual offenders are discussed. PMID- 22667812 TI - Field reliability of the SAVRY with juvenile probation officers: Implications for training. AB - Two complimentary studies were conducted to investigate the inter-rater reliability and performance of juvenile justice personnel when conducting the Structured Assessment of Violence Risk for Youth (SAVRY). Study 1 reports the performance on four standardized vignettes of 408 juvenile probation officers (JPOs) and social workers rating the SAVRY as part of their training. JPOs had high agreement with the expert consensus on the SAVRY rating of overall risk and total scores, but those trained by a peer master trainer outperformed those trained by an expert. Study 2 examined the field reliability of the SAVRY on 80 young offender cases rated by a JPO and a trained research assistant. In the field, intra-class correlation coefficients were 'excellent' for SAVRY total and most domain scores, and were 'good' for overall risk ratings. Results suggest that the SAVRY and structured professional judgment can be used reliably in the field by juvenile justice personnel and is comparable to reliability indices reported in more lab-like research studies; however, replication is essential. PMID- 22667813 TI - A Bayesian approach to the group versus individual prediction controversy in actuarial risk assessment. AB - Recent attempts to indict the use of actuarial risk assessment instruments have relied on confidence intervals to demonstrate that risk estimates derived at the group level do not necessarily apply to any specific individual within that group. This article contends that frequentist confidence intervals are inapposite to the current debate. Instead, Bayesian credible intervals are necessary-in principle-to accomplish what commentators are concerned about: describing the precision of an actuarial risk estimate. After illustrating both the calculation and interpretation of credible intervals, this article shows how such intervals can be used to characterize the precision of actuarial risk estimates. It then explores the legal implications of wide and overlapping intervals. Contrary to what detractors claim, the fact that risk estimate intervals overlap is not a germane to legal (logical) relevance, and therefore actuarial risk estimates cannot be per se "inadmissible" on this basis. PMID- 22667814 TI - Sequential lineup presentation promotes less-biased criterion setting but does not improve discriminability. AB - When compared with simultaneous lineup presentation, sequential presentation has been shown to reduce false identifications to a greater extent than it reduces correct identifications. However, there has been much debate about whether this difference in identification performance represents improved discriminability or more conservative responding. In this research, data from 22 experiments that compared sequential and simultaneous lineups were analyzed using a compound signal-detection model, which is specifically designed to describe decision making performance on tasks such as eyewitness identification tests. Sequential (cf. simultaneous) presentation did not influence discriminability, but produced a conservative shift in response bias that resulted in less-biased choosing for sequential than simultaneous lineups. These results inform understanding of the effects of lineup presentation mode on eyewitness identification decisions. PMID- 22667815 TI - Isomers of metal-organic complex arrays. AB - Three metal-organic complex arrays (MOCAs) with a specific sequence of metal centers as well as that of amino acid units were synthesized. These MOCAs are also isomers exhibiting a gelation capability dependent on the location of the metal complexes in the arrays. PMID- 22667816 TI - Enhanced dewatering of polyelectrolyte nanocomposites by hydrophobic polyelectrolytes. AB - We demonstrate that increasing the hydrophobic environment around the charge center of a polyelectrolyte (PE) not only decreases the water content of an adsorbed PE layer but can even dewater up to ~50% of an initially hydrated substrate. The results of this work are expected to yield new stratagies to dewater PE systems and have potential applications in mineral recovery, paper manufacturing, and biomedical materials. Adsorption of a series of cationically derivatized dextran polyelectrolytes onto sulfated nanocrystalline cellulose (SNC) has been studied using quartz crystal microbalance with dissipation monitoring (QCM-D) and surface plasmon resonance (SPR). Synthesized samples of (N,N-dimethylamino)ethyldextran (DMAE-Dex), (N,N-diethylamino)ethyldextran (DEAE Dex), and (N,N-diisopropylamino)ethyldextran (DIAE-Dex) had degrees of substitution (DS) ranging from 0.05 to 0.82. DMAE-Dex, DEAE-Dex, and DIAE-Dex all showed decreasing adsorption onto SNC and decreasing water content of the adsorbed film with increasing DS. Additionally, DEAE-Dex and DIAE-Dex films adsorbed onto SNC contained less water than DMAE-Dex films with the same DS. Interestingly, QCM-D results for high DS DIAE-Dex adsorbed onto SNC revealed mass loss, whereas SPR results clearly showed DIAE-Dex adsorbed. These observations were consistent with dehydration of the SNC substrate. This study indicates that the water content of the substrate could be tailored by controlling the DS and hydrophobic character of the adsorbed polyelectrolytes. PMID- 22667817 TI - New iron-based mixed-polyanion cathodes for lithium and sodium rechargeable batteries: combined first principles calculations and experimental study. AB - New iron-based mixed-polyanion compounds Li(x)Na(4-x)Fe(3)(PO(4))(2)(P(2)O(7)) (x = 0-3) were synthesized, and their crystal structures were determined. The new compounds contained three-dimensional (3D)sodium/lithium paths supported by P(2)O(7) pillars in the crystal. First principles calculations identified the complex 3D paths with their activation barriers and revealed them as fast ionic conductors. The reversible electrode operation was found in both Li and Na cells with capacities of one-electron reaction per Fe atom, 140 and 129 mAh g(-1), respectively. The redox potential of each phase was ~3.4 V (vs Li) for the Li-ion cell and ~3.2 V (vs Na) for the Na-ion cell. The properties of high power, small volume change, and high thermal stability were also recognized, presenting this new compound as a potential competitor to other iron-based electrodes such as Li(2)FeP(2)O(7), Li(2)FePO(4)F, and LiFePO(4). PMID- 22667818 TI - Iodate and iodo-trihalomethane formation during chlorination of iodide-containing waters: role of bromide. AB - The kinetics of iodate formation is a critical factor in mitigation of the formation of potentially toxic and off flavor causing iodoorganic compounds during chlorination. This study demonstrates that the formation of bromine through the oxidation of bromide by chlorine significantly enhances the oxidation of iodide to iodate in a bromide-catalyzed process. The pH-dependent kinetics revealed species specific rate constants of k(HOBr + IO(-)) = 1.9 * 10(6) M(-1) s(-1), k(BrO(-) + IO(-)) = 1.8 * 10(3) M(-1) s(-1), and k(HOBr + HOI) < 1 M(-1) s(-1). The kinetics and the yield of iodate formation in natural waters depend mainly on the naturally occurring bromide and the type and concentration of dissolved organic matter (DOM). The process of free chlorine exposure followed by ammonia addition revealed that the formation of iodo-trihalomethanes (I-THMs), especially iodoform, was greatly reduced by an increase of free chlorine exposure and an increase of the Br(-)/I(-) ratio. In water from the Great Southern River (with a bromide concentration of 200 MUg/L), the relative I-incorporation in I THMs decreased from 18 to 2% when the free chlorine contact time was increased from 2 to 20 min (chlorine dose of 1 mg Cl(2)/L). This observation is inversely correlated with the conversion of iodide to iodate, which increased from 10 to nearly 90%. Increasing bromide concentration also increased the conversion of iodide to iodate: from 45 to nearly 90% with a bromide concentration of 40 and 200 MUg/L, respectively, and a prechlorination time of 20 min, while the I incorporation in I-THMs decreased from 10 to 2%. PMID- 22667819 TI - An intramolecular [2 + 2] cycloaddition of ketenimines via palladium-catalyzed rearrangements of N-allyl-ynamides. AB - A cascade of Pd-catalyzed N-to-C allyl transfer-intramolecular ketenimine-[2 + 2] cycloadditions of N-allyl ynamides is described. This tandem sequence is highly stereoselective and the [2 + 2] cycloaddition could be rendered in a crossed or fused manner depending on alkene substitutions, leading to bridged and fused bicycloimines. PMID- 22667820 TI - Quantitative in vitro to in vivo extrapolation of cell-based toxicity assay results. AB - The field of toxicology is currently undergoing a global paradigm shift to use of in vitro approaches for assessing the risks of chemicals and drugs in a more mechanistic and high throughput manner than current approaches relying primarily on in vivo testing. However, reliance on in vitro data entails a number of new challenges associated with translating the in vitro results to corresponding in vivo exposures. Physiologically based pharmacokinetic (PBPK) modeling provides an effective framework for conducting quantitative in vitro to in vivo extrapolation (QIVIVE). Their physiological structure facilitates the incorporation of in silico- and in vitro-derived chemical-specific parameters in order to predict in vivo absorption, distribution, metabolism and excretion. In particular, the combination of in silico- and in vitro parameter estimation with PBPK modeling can be used to predict the in vivo exposure conditions that would produce chemical concentrations in the target tissue equivalent to the concentrations at which effects were observed with in vitro assays of tissue/organ toxicity. This review describes the various elements of QIVIVE and highlights key aspects of the process, with an emphasis on extrapolation of in vitro metabolism data to predict in vivo clearance as the key element. Other important elements include characterization of free concentration in the toxicity assay and potential complications associated with intestinal absorption and renal clearance. Examples of successful QIVIVE approaches are described ranging from a simple steady-state approach that is suitable for a high throughput environment to more complicated approaches requiring full PBPK models. PMID- 22667821 TI - Spontaneous DNA lesions modulate DNA structural transitions occurring at nuclease hypersensitive element III(1) of the human c-myc proto-oncogene. AB - G quadruplex (G4) DNA is a noncanonical four-stranded DNA structure that can form in G repeats by stacking of planar arrays of four hydrogen-bonded guanines called G quartets, in the presence of potassium ions. In addition to a presumed function in the regulation of gene expression, G4 DNA also localizes to regions often characterized by genomic instability. This suggests that formation of this structure may interfere with DNA transactions, including processing of DNA damage at these sites. Here we have studied the effect of two spontaneous DNA lesions, the abasic site and 8-oxoguanine, on the transition from duplex to quadruplex DNA structure occurring at nuclease hypersensitive element III(1) (NHEIII(1)) of the human c-myc promoter. We show by dimethyl sulfate footprinting and RNA polymerase arrest assays that at physiological concentrations of potassium ions NHEIII(1) folds into two coexisting G4 DNA structures, myc-1245 and myc-2345, depending on which G runs are utilized for G quartet formation. We found that a single substitution of G12 of NHEIII(1) with a single abasic site or a single 8 oxoguanine prevented formation of G4 structure myc-2345 in favor of structure myc 1245, where the lesion was accommodated in a DNA loop formed by G11-AP12/(or 8 oxoG12)-G13-G14. Surprisingly, when an additional G to A base substitution was introduced at position 3 of NHEIII(1), we observed formation of myc-2345. The extent of this structural transition was modulated by the location and type of lesion within the G11-G14 repeat. Our data indicate that spontaneous lesions formed in the G4-forming sequence of c-myc NHEIII(1) affect the structural transitions occurring at this regulatory site, potentially altering transcription factor binding and DNA repair of lesions formed in this highly regulated sequence. PMID- 22667822 TI - Switching regioselectivity in the allylation of imines by N-side chain tuning. AB - A spectacular inversion of alpha- to gamma-regioselectivity in the allylzincation of imines can be achieved by fine-tuning of the N-side chain. This approach allows easy preparation of regioisomeric amines, in racemic as well as enantiopure forms. The usefulness of the method is illustrated by the parallel asymmetric syntheses of 2,3- and 2,5-diphenylpyrrolidines. PMID- 22667824 TI - Subjective visual vertical in vestibular disorders measured with the bucket test. AB - CONCLUSION: The 'bucket test' may indicate that patients with known vestibular disorders have spatial orientation deficits but due to the low receiver operating characteristics (ROC) values it is not useful for screening people for vestibular impairments. OBJECTIVES: 1) to verify that patients with unilateral peripheral vestibular weakness (UW) differ from normal subjects on the bucket test, 2) to determine if patients with unilateral benign paroxysmal positional vertigo (BPPV) differ from normal subjects, 3) to determine the sensitivity and specificity of the test. METHODS: Patients with UW (n = 25) and BPPV (n = 25) were compared to normals (n = 50). Subjects looked into a clean bucket with a vertical line on the bottom, which rested on a table. It was rotated, clockwise or counterclockwise, for three trials per direction until the subject indicated that the line was vertical. The dependent measure was the mean absolute value of the deviations from the true vertical. RESULTS: Some, but not all, patients' responses differed from normal subjects but responses also differed by age and sex. ROC values were all weak, i.e. < 0.8. No good cut-off points differentiated controls from patients. Thus, although the bucket test is useful for describing spatial deficits in patients this test is not useful for screening people for possible vestibular impairments. PMID- 22667825 TI - Pharmacological management of hypertensive emergencies and urgencies: focus on newer agents. AB - INTRODUCTION: Hypertensive crises are categorized as hypertensive emergencies and urgencies depending on the presence of acute target-organ damage; the former are potentially life-threatening medical conditions, requiring urgent treatment under close monitoring. Although several short-acting intravenous antihypertensive agents are approved for this purpose, until recently little evidence from proper trials on the relative merits of different therapies was available. AREAS COVERED: This article discusses in brief the pathophysiology, epidemiology and diagnostic approach of hypertensive crises and provides an extensive overview of established and emerging pharmacological agents for the treatment of patients with hypertensive emergencies and urgencies. EXPERT OPINION: Agents such as sodium nitroprusside, nitroglycerin and hydralazine have been used for many years as first-line options for patients with hypertensive emergencies, although their potential adverse effects and difficulties in use were well known. With time, equally potent and less toxic alternatives, including nicardipine, fenoldopam, labetalol and esmolol are increasingly used worldwide. Recently, clevidipine, a third-generation dihydropyridine calcium-channel blocker with unique pharmacodynamic and pharmacokinetic properties was added to our therapeutic armamentarium and was shown in clinical trials to reduce mortality when compared with nitroprusside. In view of such evidence, a change in pharmacological treatment practices for hypertensive crises toward newer and safer agents is warranted. PMID- 22667826 TI - Round window electrode insertion potentiates retention in the scala tympani. AB - CONCLUSIONS: The round window membrane (RWM)-intentioned approach is superior to the traditional bony cochleostomy (BC) approach in obtaining electrode placement within the scala tympani (ST). OBJECTIVE: Cochlear implant outcome is influenced by several factors, including optimal placement and retention of the electrode array within the ST. The present study aimed to assess whether the RWM route is superior to a traditional BC for placement and retention of the electrode array in the ST. METHODS: This was a prospective consecutive non-randomized comparison study. All patients were implanted with the Advanced Bionics 1J electrode array. The RWM approach (n = 32) was compared with a traditional BC group (n = 33). The outcome measure was the electrode position as judged within the scalar chambers at four points along the basal turn using postoperative computed tomography (CT). RESULTS: When the mean position scores were compared, the RWM-intentioned group had significantly more electrodes directed towards the ST compartment than the BC group (p < 0.001). The RWM electrodes achieved 94% ST retention compared with 64% for the BC group (p < 0.05). All electrodes stayed in the ST in the RWM group, whereas in the BC group 9% crossed from the ST to the scala vestibuli. PMID- 22667828 TI - Mesoscale DNA structural changes on binding and photoreaction with Ru[(TAP)2PHEHAT]2+. AB - We used scanning force microscopy (SFM) to study the binding and excited state reactions of the intercalating photoreagent Ru[(TAP)(2)PHEHAT](2+) (TAP = 1,4,5,8 tetraazaphenanthrene; PHEHAT = 1,10-phenanthrolino[5,6-b]1,4,5,8,9,12 hexaazatriphenylene) with DNA. In the ground state, this ruthenium complex combines a strong intercalative binding mode via the PHEHAT ligand, with TAP mediated hydrogen bonding capabilities. After visible irradiation, SFM imaging of the photoproducts revealed both the structural implications of photocleavages and photoadduct formation. It is found that the rate of photocleaving is strongly increased when the complex can interact with DNA via hydrogen bonding. We demonstrated that the photoadduct increases DNA rigidity, and that the photo biadduct can crosslink two separate DNA segments in supercoiled DNA. These mechanical and topological effects might have important implications in future therapeutic applications of this type of compounds. PMID- 22667827 TI - Enhanced sensitivity by nonuniform sampling enables multidimensional MAS NMR spectroscopy of protein assemblies. AB - We report dramatic sensitivity enhancements in multidimensional MAS NMR spectra by the use of nonuniform sampling (NUS) and introduce maximum entropy interpolation (MINT) processing that assures the linearity between the time and frequency domains of the NUS acquired data sets. A systematic analysis of sensitivity and resolution in 2D and 3D NUS spectra reveals that with NUS, at least 1.5- to 2-fold sensitivity enhancement can be attained in each indirect dimension without compromising the spectral resolution. These enhancements are similar to or higher than those attained by the newest-generation commercial cryogenic probes. We explore the benefits of this NUS/MaxEnt approach in proteins and protein assemblies using 1-73-(U-(13)C,(15)N)/74-108-(U-(15)N) Escherichia coli thioredoxin reassembly. We demonstrate that in thioredoxin reassembly, NUS permits acquisition of high-quality 3D-NCACX spectra, which are inaccessible with conventional sampling due to prohibitively long experiment times. Of critical importance, issues that hinder NUS-based SNR enhancement in 3D-NMR of liquids are mitigated in the study of solid samples in which theoretical enhancements on the order of 3-4 fold are accessible by compounding the NUS-based SNR enhancement of each indirect dimension. NUS/MINT is anticipated to be widely applicable and advantageous for multidimensional heteronuclear MAS NMR spectroscopy of proteins, protein assemblies, and other biological systems. PMID- 22667829 TI - Bis(oxazoline)-based coordination polymers: a recoverable system for enantioselective Henry reactions. AB - An efficient release-capture strategy for the recovery and reuse of enantioselective catalysts in the Henry reaction is described. This strategy is based on the precipitation of an insoluble coordination polymer at the end of each reaction, allowing easy separation from products. The coordination polymer is formed through aggregation of Cu(II) ions with ditopic bisoxazoline-based chiral ligands. Up to 11 catalytic cycles have been conducted keeping good yields and enantioselectivities. PMID- 22667983 TI - Amine-templated polymeric lanthanide formates: synthesis, characterization, and applications in luminescence and magnetism. AB - The novel polymeric formates of general formula [(Fmd)Ln(III)(HCOO)(4)](infinity) (Fmd(+) = NH(2)-CH(+)-NH(2); Ln = Eu (1), Gd (2), Tb (3), Dy (4)] were synthesized through solvothermal methods in formamide solutions. The compounds are isotructural; they crystallize in the orthorhombic C222(1) chiral space group. The coordination geometry at the metal centers is square antiprismatic (coordination number eight), with each formate ligand bridging adjacent lanthanide ions. The overall negative three-dimensional (3D) framework charge is balanced by the formamidinium cations sitting inside the channels along the a axis, forming extensive N-H...O hydrogen bonding with the surrounding cage. All the compounds have been characterized through single-crystal/powder X-ray diffraction, IR spectroscopy, and TG-MS analysis. Finally, their luminescence and magnetic properties have been assessed, leading to remarkable emission intensities, especially for the Tb(III) compound (Phi = 0.83), with corresponding lifetime decays in the micro (Dy) and millisecond (Tb, Eu) time scale. A weak but sizable antiferromagnetic interaction has been observed for the Gd(III) derivative. PMID- 22667984 TI - Synthesis and structural diversity of barium (N,N-dimethylamino)diboranates. AB - The reaction of a slurry of BaBr(2) in a minimal amount of tetrahydrofuran (THF) with 2 equiv of Na(H(3)BNMe(2)BH(3)) in diethyl ether followed by crystallization from diethyl ether at -20 degrees C yields crystals of Ba(H(3)BNMe(2)BH(3))(2)(Et(2)O)(2) (1). Drying 1 at room temperature under vacuum gives the partially desolvated analogue Ba(H(3)BNMe(2)BH(3))(2)(Et(2)O)(x) (1') as a free-flowing white solid, where the value of x varies from <0.1 to about 0.4 depending on whether desolvation is carried out with or without heating. The reaction of 1 or 1' with Lewis bases that bind more strongly to barium than diethyl ether results in the formation of new complexes Ba(H(3)BNMe(2)BH(3))(2)(L), where L = 1,2-dimethoxyethane (2), N,N,N',N' tetramethylethylenediamine (3), 12-crown-4 (4), 18-crown-6 (5), N,N,N',N' tetraethylethylenediamine (6), and N,N,N',N",N"-pentamethylethylenetriamine (7). Recrystallization of 4 and 5 from THF affords the related compounds Ba(H(3)BNMe(2)BH(3))(2)(12-crown-4)(THF).THF (4') and Ba(H(3)BNMe(2)BH(3))(2)(18 crown-6).2THF (5'). In addition, the reaction of BaBr(2) with 2 equiv of Na(H(3)BNMe(2)BH(3)) in the presence of diglyme yields Ba(H(3)BNMe(2)BH(3))(2)(diglyme)(2) (8), and the reaction of 1 with 15-crown-5 affords the diadduct [Ba(15-crown-5)(2)][H(3)BNMe(2)BH(3)](2) (9). Finally, the reaction of BaBr(2) with Na(H(3)BNMe(2)BH(3)) in THF, followed by the addition of 12-crown-4, affords the unusual salt [Na(12-crown 4)(2)][Ba(H(3)BNMe(2)BH(3))(3)(THF)(2)] (10). All of these complexes have been characterized by IR and (1)H and (11)B NMR spectroscopy, and the structures of compounds 1-3, 4', 5', and 6-10 have been determined by single-crystal X-ray diffraction. As the steric demand of the Lewis bases increases, the structure changes from polymers to dimers to monomers and then to charge-separated species. Despite the fact that several of the barium complexes are monomeric in the solid state, none is appreciably volatile up to 200 degrees C at 10(-2) Torr. PMID- 22667985 TI - Modulating nitric oxide release by S-nitrosothiol photocleavage: mechanism and substituent effects. AB - The photochemistry and photophysics of a series of S-nitrosothiols (RSNOs) have been studied computationally. The photocleavage mechanism of the model compound CH(3)SNO to release CH(3)S. and .NO was studied at the CASPT2 level resulting in a barrierless process when irradiating in the visible region (S(1)), in the near UV region (S(2)) and for photosensitized (T(1)) reaction. The absorption energy required to initiate photocleavage was calculated at the CASPT2 and B3P86 levels showing the possibility of the modulation of NO release by RSNO photoactivation as a function of the substituent R. Good correlations between the wavelengths of the lowest energy (1)(n,pi*) and (1)(pi,pi*) transitions of aryl S-nitrosothiols and the corresponding Hammett constants of the substituents have been obtained. PMID- 22667987 TI - A web-based intervention for elementary school teachers of students with attention-deficit/hyperactivity disorder (ADHD). AB - The goal of the present study was to determine whether a web-based medium is an effective tool for supporting knowledge, attitude, and behavior change in teachers of elementary school children with attention-deficit/hyperactivity disorder (ADHD). Nineteen teachers from Nova Scotia, Canada completed a 7-week intervention that consisted of presentations, web links, and discussion board activities related to different aspects of ADHD. Teachers' knowledge positively changed from pre- to post-intervention (p = .03), as did teachers' attitudes related to perceived control in their classrooms (p = .001) and competence in teaching (p < .0001). The study demonstrated that a web-based medium is a useful tool for knowledge creation and translation and has potential as a means of providing professional development to teachers about ADHD. PMID- 22667988 TI - Bipartite tetracysteine display reveals allosteric control of ligand-specific EGFR activation. AB - Aberrant activation of the epidermal growth factor receptor (EGFR), a prototypic receptor tyrosine kinase, is critical to the biology of many common cancers. The molecular events that define how EGFR transmits an extracellular ligand binding event through the membrane are not understood. Here we use a chemical tool, bipartite tetracysteine display, to report on ligand-specific conformational changes that link ligand binding and kinase activation for full-length EGFR on the mammalian cell surface. We discover that EGF binding is communicated to the cytosol through formation of an antiparallel coiled coil within the intracellular juxtamembrane (JM) domain. This conformational transition is functionally coupled to receptor activation by EGF. In contrast, TGFalpha binding is communicated to the cytosol through formation of a discrete, alternative helical interface. These findings suggest that the JM region can differentially decode extracellular signals and transmit them to the cell interior. Our results provide new insight into how EGFR communicates ligand-specific information across the membrane. PMID- 22667989 TI - Magneto-optical properties of core-shell magneto-plasmonic Au-Co(x)Fe(3 - x)O4 nanowires. AB - The magneto-optical properties of Au-Co(x)Fe(3 - x)O(4) core-shell nanowires embedded in porous alumina membranes are studied. The structures were obtained by depositing Co(x)Fe(3 - x)O(4) on the pore walls of alumina membranes by atomic layer deposition and filling the resulting nanotube with gold by electrodeposition. The effect of plasmon resonance excitation on the magneto optical activity is clearly observed as a modification of the spectral line shape of the Kerr rotation signal. PMID- 22667990 TI - Intracellular silver accumulation in Chlamydomonas reinhardtii upon exposure to carbonate coated silver nanoparticles and silver nitrate. AB - The intracellular silver accumulation ({Ag}(in)) upon exposure to carbonate coated silver nanoparticles (AgNP, 0.5-10 MUM, average diameter 29 nm) and silver nitrate (20-500 nM) was examined in the wild type and in the cell wall free mutant of the green alga Chlamydomonas reinhardtii at pH 7.5. The {Ag}(in) was measured over time up to 1 h after a wash procedure to remove silver ions (Ag(+)) and AgNP from the algal cell surface. The {Ag}(in) increased with increasing exposure time and with increasing AgNP and AgNO(3) concentrations in the exposure media, reaching steady-state concentrations between 10(-5) and 10(-3) mol L(cell)(-1). According to estimated kinetic parameters, high Ag(+) bioconcentration factors were calculated (>10(3) L L(cell)(-1)). Higher accumulation rate constants were assessed in the cell wall free mutant, indicating a protective role of the cell wall in limiting Ag(+) uptake. The bioavailability of AgNP was calculated to be low in both strains relative to Ag(+), suggesting that AgNP internalization across the cell membrane was limited. PMID- 22667991 TI - Valence tautomerism in a high-valent manganese-oxo porphyrinoid complex induced by a Lewis acid. AB - Addition of the Lewis acid Zn(2+) to (TBP(8)Cz)Mn(V)(O) induces valence tautomerization, resulting in the formation of [(TBP(8)Cz(+*))Mn(IV)(O)-Zn(2+)]. This new species was characterized by UV-vis, EPR, the Evans method, and (1)H NMR and supported by DFT calculations. Removal of Zn(2+) quantitatively restores the starting material. Electron-transfer and hydrogen-atom-transfer reactions are strongly influenced by the presence of Zn(2+). PMID- 22667992 TI - Economic evaluation of clopidogrel in acute coronary syndrome patients without ST segment elevation in Greece: a cost-utility analysis. AB - BACKGROUND: Current guidelines recommend treatment with antiplatelet and anticoagulant therapy for the secondary prevention of atherothrombotic events among patients with non-ST-segment elevation myocardial infarction (NSTEMI) or unstable angina (UA). The CURE (Clopidogrel in Unstable angina to prevent Recurrent Events) trial has shown that clopidogrel alone or in combination with aspirin is more effective in reducing the risk of atherothrombotic events than aspirin alone in NSTEMI or UA patients. However, in the current climate of financial constraints, the effectiveness of a treatment should be considered in conjunction with its long-term economic costs to determine the best possible care. OBJECTIVE: To evaluate the cost effectiveness of 1 year of treatment with clopidogrel in addition to aspirin in NSTEMI or UA patients from the third-party payer perspective in Greece. METHODS: An existing Markov model consisting of six states (NSTEMI/UA/no event, first year with stroke, history of stroke, first year with myocardial infarction [MI], history of MI and death) was adapted and extended to the Greek healthcare setting for year 2012. Utility values obtained from a Greek national study were assigned to each health state in order to estimate the quality-adjusted life-years (QALYs). Costs assigned to each health state included antiplatelet treatment cost, cost for the management of adverse events and the costs for concomitant medication, hospitalization, outpatient visits, rehabilitation and nursing. Cost effectiveness and cost utility was expressed as the cost per life-year (LY) gained and QALY gained, respectively. A probabilistic sensitivity analysis was conducted. RESULTS: The Markov analysis predicts a discounted survival of 8.27 years in the aspirin treatment group and 8.41 years in the aspirin plus clopidogrel treatment group. The corresponding discounted QALYs were 6.88 and 7.00, respectively. The cumulated lifetime costs per patient were ? 18 779 and ? 19 191, for the aspirin and aspirin plus clopidogrel treatment arms, respectively. The incremental cost-effectiveness ratio (ICER) with the addition of clopidogrel was &U20AC;2951 for each LY saved and &U20AC;3541 for each QALY saved. Finally, clopidogrel plus aspirin was found to be cost effective in more than 95% of simulated samples at a threshold of &U20AC;7000 per discounted QALY gained. CONCLUSION: One-year treatment with clopidogrel in addition to aspirin is a cost-effective treatment option for secondary prevention in patients with acute coronary syndrome without ST-segment elevation in Greece. PMID- 22667993 TI - Tumor-stromal interactions in lung cancer: novel candidate targets for therapeutic intervention. AB - INTRODUCTION: Lung cancer is the leading cause of cancer deaths worldwide. Although standard treatment regimens have produced promising results with neoadjuvant and adjuvant strategies, outcomes for patients with lung cancer are still considered disappointing. Recent data provide evidence that the tumor stromal environment is a leading player in carcinogenesis, not just a supporting tumor compartment. AREAS COVERED: This article reviews the current understanding of the lung cancer microenvironment and the complex bidirectional interplay between the tumor and lung microenvironment in non-small cell lung cancer (NSCLC). In particular, this review emphasizes the role of fibroblasts, mesenchymal stem cells and myeloid cells as well as mediators and molecular pathways regulated by these cells within the tumor microenvironment (TME) that contribute to lung tumor initiation, progression and metastasis. In addition, this review also summarizes the therapeutic strategies currently being applied in preclinical and clinical trials. EXPERT OPINION: Considering the recent advances in understanding lung tumor stroma, lung cancer progression could be effectively hampered by combining cytotoxic strategies with therapies that target the TME. However, more preclinical and clinical research is needed to prove the efficacy of this strategy for treating NSCLC. PMID- 22667994 TI - Hearing and otitis media with effusion in young adults with cleft lip and palate. AB - CONCLUSION: Speech recognition in noise is affected when otitis media with effusion (OME) is present in young adults with unilateral cleft lip and palate. OBJECTIVE: The objective of this study was to describe the hearing and performance on auditory tasks of young adults with unilateral cleft lip and palate as compared to young adults without cleft lip and palate. METHODS: Twenty six young adults with unilateral cleft lip and palate and 23 young adults without cleft lip and palate participated in the study. Pure tone audiometry, tympanometry, speech recognition in noise at the word and sentence level, and masking level difference were examined. RESULTS: Results revealed elevated hearing thresholds in the young adults with cleft lip and palate as compared with young adults without cleft lip and palate. No differences concerning speech recognition in noise and binaural processing were observed between the young adults with cleft lip and palate and those without. However, there was poorer speech recognition performance in those adults with unilateral cleft lip and palate and OME on the day of testing as compared with young adults with unilateral cleft lip and palate without OME on the day of testing. PMID- 22667995 TI - Phase transitions of pea starch over a wide range of water content. AB - The phase transitions of pea starch over a wide range of water content were investigated by differential scanning calorimetry (DSC). Swelling of starch granules increased progressively with increasing water content. The main endotherm G broadened progressively with increasing water content up to 94.5 wt % (water:starch ratio 15:1), above which it became too broad to define. The corresponding peak and conclusion temperatures and enthalpy change increased with increasing water content. Scanning electron microscopy (SEM) showed that, at a water:starch ratio of 2:1 (water content of 70.7 wt %), starch granules only swelled partially with discernible granular contours still clearly evident. The results of swelling power tests and SEM images revealed that the endotherm G obtained at a water:starch ratio of 2:1 represented only partial swelling of starch granules. The transition from a narrow to broad endotherm G was interpreted to reflect the thermal transition behavior progressing from limited swelling to maximum swelling and then partial dissolution and leaching of starch polymers from the granules. PMID- 22667996 TI - Developing physical exposure-based back injury risk models applicable to manual handling jobs in distribution centers. AB - Using our ultrasound-based "Moment Monitor," exposures to biomechanical low back disorder risk factors were quantified in 195 volunteers who worked in 50 different distribution center jobs. Low back injury rates, determined from a retrospective examination of each company's Occupational Safety and Health Administration (OSHA) 300 records over the 3-year period immediately prior to data collection, were used to classify each job's back injury risk level. The analyses focused on the factors differentiating the high-risk jobs (those having had 12 or more back injuries/200,000 hr of exposure) from the low-risk jobs (those defined as having no back injuries in the preceding 3 years). Univariate analyses indicated that measures of load moment exposure and force application could distinguish between high (n = 15) and low (n = 15) back injury risk distribution center jobs. A three-factor multiple logistic regression model capable of predicting high-risk jobs with very good sensitivity (87%) and specificity (73%) indicated that risk could be assessed using the mean across the sampled lifts of the peak forward and or lateral bending dynamic load moments that occurred during each lift, the mean of the peak push/pull forces across the sampled lifts, and the mean duration of the non-load exposure periods. A surrogate model, one that does not require the Moment Monitor equipment to assess a job's back injury risk, was identified although with some compromise in model sensitivity relative to the original model. PMID- 22667997 TI - Platinum concentration in sentinel lymph nodes after preoperative intra-arterial cisplatin chemotherapy targeting primary tongue cancer. AB - CONCLUSION: We conclude that intra-arterially injected cisplatin passed via lymph flow into sentinel nodes (SNs) as the platinum concentration in the SNs was higher than that in the non-sentinel nodes (NSNs). It is possible that preoperative intra-arterial chemotherapy targeting primary cancer also has a therapeutic effect on subclinical metastatic SNs. OBJECTIVES: Intra-arterial chemoradiotherapy has been reported to be effective against not only primary tumors but also nodal metastases. We considered the hypothesis that intra arterially injected cisplatin passed via lymph flow into regional nodes. This study aimed to investigate intra-arterially injected cisplatin distribution to regional nodes by comparing platinum concentrations in SNs and NSNs. METHODS: Five patients with T1-2 N0 tongue cancer were treated with preoperative intra arterial chemotherapy (cisplatin, 100 mg/m(2)) targeting primary cancer. Partial glossectomy together with SN biopsy and elective neck dissection were performed 2 weeks after intra-arterial chemotherapy. Platinum concentrations in the lymph nodes were measured using a Zeeman atomic absorption spectrometer. RESULTS: Thirteen SNs were harvested together with eight NSNs from the areas adjacent to the SNs. Platinum concentrations were then measured, revealing a significant difference in platinum concentration between the SNs and the NSNs (mean +/- SD, 0.682 +/- 0.246 ug/g vs 0.506 +/- 0.274 ug/g; p = 0.049). PMID- 22667999 TI - Synthesis of 2,5-disubstituted 6-azaindoles from substituted aziridines via intramolecular cyclization. AB - A new and efficient preparation of pharmacologically and biologically important 2,5-disubstituted 6-azaindoles was achieved from cyclizations of aziridin-2-yl dipropargylic alcohols as adducts of two propargyl groups to ethyl 1 benzylaziridine-2-carboxylate. The sequential cyclizations include pyrrole formation and a novel base-catalyzed intramolecular acetylenic Schmidt reaction. PMID- 22668000 TI - No evidence of telomere length attrition in newborns from high level natural background radiation areas in Kerala coast, south west India. AB - PURPOSE: The tandemly repeated hexamers (TTAGGG)n present at the telomeric ends protect the human genome from a variety of environmental exposures including ionizing radiation. In order to find out the effect of chronic low dose radiation exposure, we have determined telomere length among newborns from high level natural radiation areas (HLNRA) of the Kerala coast in South west India. METHODOLOGY: Umbilical cord blood samples were collected from 128 newborns from HLNRA and 43 newborns from normal level natural radiation areas (NLNRA) and genomic DNA was isolated using a salt precipitation method. The mean telomere length was determined using SYBR green-based real time quantitative Polymerase chain reaction (qPCR), where telomere gene specific (T) and single copy gene specific (S) primers were used. The average of telomere versus single copy gene (T/S) ratio was calculated which was proportional to telomere length of each individual. RESULTS: The mean relative telomere length was found to be 1.03 +/- 0.01 (95% CI, 0.99-1.05) and 1.10 +/- 0.03 (95% CI, 1.04-1.17) in HLNRA and NLNRA newborns, respectively (P > 0.05). Based on the level of background radiation dose, samples were divided into four groups, i.e., NLNRA: < 1.50 mGy/year and three HNLRA groups: 1.51-3.00 mGy/year, 3.01-5.00 mGy/year, and > 5.00 mGy/year. The mean relative telomere length in these groups were found to be 1.10 +/- 0.03 (95% CI, 1.03-1.17), 0.98 +/- 0.01 (95% CI, 0.95-1.01), 1.05 +/- 0.02 (95% CI, 1.01-1.10) and 1.07 +/- 0.03 (95% CI, 1.04-1.10), respectively. No significant difference was observed between the mean telomere length of male and female newborns. CONCLUSIONS: The elevated level of natural chronic background radiation prevailing in Kerala coast did not show any significant effect on telomere length of newborns. To our knowledge, this is the first report on newborn telomere length from a high level natural radiation area. PMID- 22668001 TI - Rapid mobilization of membrane lipids in wheat leaf sheaths during incompatible interactions with Hessian fly. AB - Hessian fly (HF) is a biotrophic insect that interacts with wheat on a gene-for gene basis. We profiled changes in membrane lipids in two isogenic wheat lines: a susceptible line and its backcrossed offspring containing the resistance gene H13. Our results revealed a 32 to 45% reduction in total concentrations of 129 lipid species in resistant plants during incompatible interactions within 24 h after HF attack. A smaller and delayed response was observed in susceptible plants during compatible interactions. Microarray and real-time polymerase chain reaction analyses of 168 lipid-metabolism-related transcripts revealed that the abundance of many of these transcripts increased rapidly in resistant plants after HF attack but did not change in susceptible plants. In association with the rapid mobilization of membrane lipids, the concentrations of some fatty acids and 12-oxo-phytodienoic acid (OPDA) increased specifically in resistant plants. Exogenous application of OPDA increased mortality of HF larvae significantly. Collectively, our data, along with previously published results, indicate that the lipids were mobilized through lipolysis, producing free fatty acids, which were likely further converted into oxylipins and other defense molecules. Our results suggest that rapid mobilization of membrane lipids constitutes an important step for wheat to defend against HF attack. PMID- 22668002 TI - Nonlegume Parasponia andersonii deploys a broad rhizobium host range strategy resulting in largely variable symbiotic effectiveness. AB - The non-legume genus Parasponia has evolved the rhizobium symbiosis independent from legumes and has done so only recently. We aim to study the promiscuity of such newly evolved symbiotic engagement and determine the symbiotic effectiveness of infecting rhizobium species. It was found that Parasponia andersonii can be nodulated by a broad range of rhizobia belonging to four different genera, and therefore, we conclude that this non-legume is highly promiscuous for rhizobial engagement. A possible drawback of this high promiscuity is that low-efficient strains can infect nodules as well. The strains identified displayed a range in nitrogen-fixation effectiveness, including a very inefficient rhizobium species, Rhizobium tropici WUR1. Because this species is able to make effective nodules on two different legume species, it suggests that the ineffectiveness of P. andersonii nodules is the result of the incompatibility between both partners. In P. andersonii nodules, rhizobia of this strain become embedded in a dense matrix but remain vital. This suggests that sanctions or genetic control against underperforming microsymbionts may not be effective in Parasponia spp. Therefore, we argue that the Parasponia-rhizobium symbiosis is a delicate balance between mutual benefits and parasitic colonization. PMID- 22668003 TI - Collisional activation of [14Pro+2H]2+ clusters: chiral dependence of evaporation and fission processes. AB - Ion mobility/mass spectrometry techniques are used to investigate the dissociation of the small proline cluster [14Pro+2H](2+) produced by electrospray ionization. While this cluster is known to prefer heterochiral compositions (i.e., mixed L- and D-compositions, J. Phys. Chem. A, submitted for publication), it is possible to produce homochiral forms by electrospraying solutions containing only L- or D-proline. Differences in the measured cross sections for [14Pro+2H](2+) produced from enantiomerically pure (100% l or 100% d) or racemic (50:50 l/d) solutions indicate that homochiral and heterochiral clusters have different structures. Upon low-energy collisional activation, both the heterochiral and homochiral doubly charged structures evaporate neutral proline monomers, resulting in the formation of [xPro+2H](2+) ions (where x = 9-13). At higher activation energies, there is evidence that these smaller clusters (primarily [10Pro+2H](2+)) fission to produce [xPro+H](+) (where x = 1-6). Analysis of product ion intensities reveals a strong chiral preference associated with fissioning. Products of evaporation also show a chiral dependence but to a lesser extent. PMID- 22668004 TI - Does covalency increase or decrease across the actinide series? Implications for minor actinide partitioning. AB - A covalent chemical bond carries the connotation of overlap of atomic orbitals between bonded atoms, leading to a buildup of the electron density in the internuclear region. Stabilization of the valence 5f orbitals as the actinide series is crossed leads, in compounds of the minor actinides americium and curium, to their becoming approximately degenerate with the highest occupied ligand levels and hence to the unusual situation in which the resultant valence molecular orbitals have significant contributions from both actinide and the ligand yet in which there is little atomic orbital overlap. In such cases, the traditional quantum-chemical tools for assessing the covalency, e.g., population analysis and spin densities, predict significant metal-ligand covalency, although whether this orbital mixing is really covalency in the generally accepted chemical view is an interesting question. This review discusses our recent analyses of the bonding in AnCp3 and AnCp4 (An = Th-Cm; Cp = eta(5)-C5H5) using both the traditional tools and also topological analysis of the electron density via the quantum theory of atoms-in-molecules. I will show that the two approaches yield rather different conclusions and suggest that care must be taken when using quantum chemistry to assess metal-ligand covalency in this part of the periodic table. The implications of this work for minor actinide partitioning from nuclear wastes are discussed; minor actinide extractant ligands based on nitrogen donors have received much attention in recent years, as have comparisons of the extent of covalency in actinide-nitrogen bonding with that in analogous lanthanide systems via quantum-chemical studies employing the traditional tools for assessing the covalency. PMID- 22668005 TI - Toward fast determination of protein stability maps: experimental and theoretical analysis of mutants of a Nocardiopsis prasina serine protease. AB - The stability of serine proteases is of major importance for their application in industrial processes. Here we study the determinants of the stability of a Nocardiopsis prasina serine protease using fast residual activity assays, a feature classification algorithm, and structure-based energy calculation algorithms for 121 micropurified mutant enzyme clones containing multiple point mutations. Using a multivariate regression analysis, we deconvolute the data for the mutant clones and find that mutations of residues Asn47 and Pro124 are deleterious to the stability of the enzyme. Both of these residues are situated in loops that are known to be important for the stability of the highly homologous alpha-lytic protease. Structure-based energy calculations with PEATSA give a good general agreement with the trend of experimentally measured values but also identify a number of clones that the algorithm fails to predict correctly. We discuss the significance of the results in relation to the structure and function of closely related proteases, comment on the optimal experimental design when performing high-throughput experiments for characterizing the determinants of protein stability, and discuss the performance of structure-based energy calculations with complex data sets such as the one presented here. PMID- 22667998 TI - The cystine/glutamate antiporter system x(c)(-) in health and disease: from molecular mechanisms to novel therapeutic opportunities. AB - The antiporter system x(c)(-) imports the amino acid cystine, the oxidized form of cysteine, into cells with a 1:1 counter-transport of glutamate. It is composed of a light chain, xCT, and a heavy chain, 4F2 heavy chain (4F2hc), and, thus, belongs to the family of heterodimeric amino acid transporters. Cysteine is the rate-limiting substrate for the important antioxidant glutathione (GSH) and, along with cystine, it also forms a key redox couple on its own. Glutamate is a major neurotransmitter in the central nervous system (CNS). By phylogenetic analysis, we show that system x(c)(-) is a rather evolutionarily new amino acid transport system. In addition, we summarize the current knowledge regarding the molecular mechanisms that regulate system x(c)(-), including the transcriptional regulation of the xCT light chain, posttranscriptional mechanisms, and pharmacological inhibitors of system x(c)(-). Moreover, the roles of system x(c)( ) in regulating GSH levels, the redox state of the extracellular cystine/cysteine redox couple, and extracellular glutamate levels are discussed. In vitro, glutamate-mediated system x(c)(-) inhibition leads to neuronal cell death, a paradigm called oxidative glutamate toxicity, which has successfully been used to identify neuroprotective compounds. In vivo, xCT has a rather restricted expression pattern with the highest levels in the CNS and parts of the immune system. System x(c)(-) is also present in the eye. Moreover, an elevated expression of xCT has been reported in cancer. We highlight the diverse roles of system x(c)(-) in the regulation of the immune response, in various aspects of cancer and in the eye and the CNS. PMID- 22668006 TI - Cu-Mn spinel oxide catalyzed regioselective halogenation of phenols and N heteroarenes. AB - A novel simple, mild chemo- and regioselective method has been developed for the halogenation of phenols using Cu-Mn spinel oxide as a catalyst and N halosuccinimide as halogenating agent. In the presence of Cu-Mn spinel oxide B, both electron-withdrawing and electron-donating groups bearing phenols gave monohalogenated products in good to excellent yields with highest para selectivity. The para-substituted phenol gave monohalogenated product with good yield and ortho-selectivity. N-Heteroarenes such as indoles and imidazoles also gave monohalogenated products with high selectivity. Unlike the copper-catalyzed halogenation, the present method works well with electron-withdrawing group bearing phenols and gives comparatively better yields and selectivity. The Cu-Mn spinel catalyst is robust and reused three times under optimized conditions without any loss in catalytic activity. Nonphenolics did not undergo this transformation. PMID- 22668007 TI - Positively charged mini-protein Zbasic2 as a highly efficient silica binding module: opportunities for enzyme immobilization on unmodified silica supports. AB - Silica is a highly attractive support material for protein immobilization in a wide range of biotechnological and biomedical-analytical applications. Without suitable derivatization, however, the silica surface is not generally usable for attachment of proteins. We show here that Z(basic2) (a three alpha-helix bundle mini-protein of 7 kDa size that exposes clustered positive charges from multiple arginine residues on one side) functions as highly efficient silica binding module (SBM), allowing chimeras of target protein with SBM to become very tightly attached to underivatized glass at physiological pH conditions. We used two enzymes, d-amino acid oxidase and sucrose phosphorylase, to demonstrate direct immobilization of Z(basic2) protein from complex biological samples with extremely high selectivity. Immobilized enzymes displayed full biological activity, suggesting that their binding to the glass surface had occurred in a preferred orientation via the SBM. We also show that charge complementarity was the main principle of affinity between SBM and glass surface, and Z(basic2) proteins were bound in a very strong, yet fully reversible manner, presumably through multipoint noncovalent interactions. Z(basic2) proteins were immobilized on porous glass in a loading of 30 mg protein/g support or higher, showing that attachment via the SBM combines excellent binding selectivity with a technically useful binding capacity. Therefore, Z(basic2) and silica constitute a fully orthogonal pair of binding module and insoluble support for oriented protein immobilization, and this opens up new opportunities for the application of silica based materials in the development of supported heterogeneous biocatalysts. PMID- 22668008 TI - Water desalination across nanoporous graphene. AB - We show that nanometer-scale pores in single-layer freestanding graphene can effectively filter NaCl salt from water. Using classical molecular dynamics, we report the desalination performance of such membranes as a function of pore size, chemical functionalization, and applied pressure. Our results indicate that the membrane's ability to prevent the salt passage depends critically on pore diameter with adequately sized pores allowing for water flow while blocking ions. Further, an investigation into the role of chemical functional groups bonded to the edges of graphene pores suggests that commonly occurring hydroxyl groups can roughly double the water flux thanks to their hydrophilic character. The increase in water flux comes at the expense of less consistent salt rejection performance, which we attribute to the ability of hydroxyl functional groups to substitute for water molecules in the hydration shell of the ions. Overall, our results indicate that the water permeability of this material is several orders of magnitude higher than conventional reverse osmosis membranes, and that nanoporous graphene may have a valuable role to play for water purification. PMID- 22668009 TI - Single molecule multiphotochromism with diarylethenes. AB - In single photochromes, the two isomers that are interconverted in photoinduced reactions can serve as on and off states in a molecular switching device. The addition of several photochromic moieties onto a single molecule can allow the processing of more complex logical patterns. For example, an asymmetric triad could, in principle, store a byte, rather than a bit, of data. Because of the potential impact of multiphotochromic molecules in many research areas, over the past decade several groups have synthesized these coupled structures. The targets are easily addressable molecules that display increased contrast between the on and off states and in which all isomers have significantly distinguishable optical signatures. In this Account, we provide an overview of the multiswitchable molecular systems that incorporate at least one diarylethene group, which is the most successful thermally stable (P-type) organic photochrome. Up to this point, most systems have presented significant limitations. First of all, the reversibility of the processes is hindered by several side reactions more frequently than for single photochromes. Second, switching one part of the compound impedes the photoreactivity of other fragments in approximately 50% of the cases, and maximizing the electronic communication increases the probability of partial activity. In addition, most of the few synthesized operative systems only demonstrate cumulative absorption spectra rather than new features. Finally, it is impossible to selectively induce a chosen conversion because one wavelength might trigger several processes. We also emphasize the promising successes of asymmetric diarylethene dimers and trimers and molecules that combine two families of photochromes, such as diarylethene added to fulgimide or phenoxy-naphthacenequinone. In that framework, theoretical simulations offer complementary tools to investigate these structures, both to obtain structure/property relationships and to propose paths for the design of more efficient molecules. However, due to the size of the systems, researchers can only apply semiquantitative models. The investigation of the absorption spectra of the photochromes with time-dependent density functional theory (TD DFT), the analysis of the topology of the LUMO + n (typically n = 1) of the closed-open hybrid, and an estimate of the steric stress in the hypothetical (ground-state) closed-closed structure serve as a useful combination of parameters to obtain initial insights regarding the photocyclization of the different open diarylethene groups. Nevertheless, because a first-order qualitative approach does not explore the potential energy surface of the photoexcited states, it remains inadequate for the investigation of some molecules. PMID- 22668010 TI - Insulin infusion for hyperglycaemia in very preterm infants appears safe with no effect on morbidity, mortality and long-term neurodevelopmental outcome. AB - BACKGROUND/OBJECTIVE: Hyperglycaemia is common in very premature neonates and is associated with increased risk of intraventricular haemorrhage, necrotising enterocolitis, sepsis and death. Administration of insulin may risk hypoglycaemia and associated complications. To determine effects of insulin infusions in very premature infants on morbidity, mortality and long-term neurodevelopmental outcome. METHODS: Retrospective audit of 97 infants delivered at <29 weeks gestation and admitted to The Canberra Hospital NICU. Data on insulin treatment, Blood Glucose Levels (BGL's) prior and during insulin therapy, episodes of significant hypoglycaemia and neurodevelopmental outcome at 12 months corrected age was collected. RESULTS: 17 (17.5%) neonates received insulin. Episodes of hypoglycaemia were infrequent (1.3%, 95% CI 0.5-2.9). Multiple regression analysis showed that insulin treatment was not associated with an increased risk of retinopathy of prematurity (OR 3.6, 95% CI 0.4-32.3) or mortality (OR 1.2, 95% CI 0.29-5.0). No significant difference in 12 month neurodevelopmental or anthropometric outcomes was detected in infants who received insulin. CONCLUSION: Insulin infusions for hyperglycaemia appear to be safe with infrequent episodes of hypoglycaemia, no increased risk of morbidity or mortality and no adverse effect on long-term neurodevelopmental outcome. PMID- 22668011 TI - The clinicopathological significance of Bax and Bcl-2 protein expression with tumor infiltrating lymphocytes in ovarian carcinoma. AB - The aim of the study was to establish the prognostic and predictive value of Bax and Bcl-2 proteins in conjunction with the host immune response in primary epithelial ovarian carcinoma.83 patients were evaluated. Immunohistochemical staining was performed using anti-Bcl-2 (Dako; clone 124) and anti-Bax (Springbio; E17994) monoclonal antibodies. Additionally, the number of lymphocytes within tumor stroma lymphocyte nests were counted. Bcl-2 protein expression was lower in advanced stage than early stage (p= 0.005). High (H) Bax expression was associated with longer overall survival (OS) than lower (L) Bax expression (p=0.03). The OS of the (L) Bax/(L) Bcl-2 group was shorter than (H) Bax/(L) Bcl-2 group in advanced stage (p=0.05). The platinum-sensitive group had a statistically significant tendency for high Bax expression (p=0.04). Furthermore, the intensity of the lymphocyte infiltration was associated with tumor differentiation (p= 0.003). Our data suggests that (H) Bax protein expression prolongs survival, predicts platinum sensitivity and can be used after confirmation of this hypothesis in further prospective studies. The combined evaluation of Bax and Bcl-2 protein expression may provide additional significant prognostic information. The quantity of lymphocyte infiltration could be important for prognostic outcome. PMID- 22668012 TI - Mutational and expressional analyses of STAG2 gene in solid cancers. AB - Aneuploidy is frequently observed in cancers and is considered a crucial mechanism in cancer development. STAG2 is a gene that encodes a component of cohesion complex required for normal chromosomal segregation. Recently, somatic mutation of STAG2 gene and loss of STAG2 protein have been reported in glioblastoma, Ewing's sarcoma and melanoma. The aim of this study was to see whether such alterations of STAG2 are also common in other cancers. In this study, we analyzed STAG2 somatic mutation in 45 colorectal carcinomas (CRC), 45 gastric carcinomas (GC), 45 breast carcinomas, 45 non-small cell lung cancers and 45 prostate carcinomas (PCA) by single-strand conformation polymorphism. We analyzed also STAG2 protein expression in 100 GC, 103 CRC and 107 PCA by immunohistochemistry. STAG2 protein was well expressed in normal stomach, colon and prostate epithelial cells, while it was lost in 27% of GC, 23% of CRC and 30% of PCA. The loss of STAG2 was observed irrespective of subtypes, stages and grades of the cancers. However, we could not find any STAG2 mutations in these cancers. The loss of expression of STAG2 in GC, CRC and PCA tissues compared to their corresponding normal cells indicates that STAG2 loss is common in carcinomas as well. The data suggest also that loss of expression of STAG2, but not somatic mutation, might be responsible to STAG2 inactivation and is common in studied types of carcinomas. PMID- 22668013 TI - Perioperative interstitial CT-based brachytherapy boost in breast cancer patients with breast conservation after neoadjuvant chemotherapy. AB - Intraoperative placement of catheters in the tumor bed during breast-conserving surgery (BCS) enables postponed targeted boost irradiation in high risk breast cancer patients. Twenty-three patients with high risk breast cancer underwent neoadjuvant chemotherapy and multifractionated perioperative brachytherapy as a boost to the tumor bed using three-dimensional (3D) CT-based planning. Plastic catheters for brachytherapy were implanted during surgery and targeted irradiation was delivered in the course of 2-3 weeks. Acute and late toxicities were scored according to the RTOG Common Toxicity Criteria. Cosmetic outcomes were assessed using the Harvard criteria. No major perioperative complications were recorded. Circumscribed wound infection occurred in one patient (4.3%). Only 3 patients (13%) experienced acute skin toxicity Grade 1. We observed no teleangiectasias or pigmentations. The cosmetic outcome at last follow-up visit was rated as excellent/good, in 82.6%, fair, in 13% and poor in 4.4% of patients, respectively. There was no evidence of disease recurrence after median follow-up of 43. 4 months. Systematic integration of the perioperative fractionated 3D CT based HDR brachytherapy as a boost for patients with breast cancer after BCS is feasible and seems safe. It might be beneficial especially for women with high risk of local recurrence. PMID- 22668014 TI - Biomarkers in the lung cancer diagnosis: a clinical perspective. AB - The propensity for tumor biomarkers to be detected in serum at an early disease stage has become an area of interest for clinicians. This study aimed to evaluate the efficiency of 7 tumor biomarkers, namely, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cytokeratin 19 (CYFRA-21-1), alpha-fetoprotein, carbohydrate antigen-125 (CA-125), carbohydrate antigen-19.9 (CA-19.9), and ferritin, independently or in combination for the diagnosis of lung cancer. Electrochemiluminescence immunization was used to determine biomarker levels expressed in 530 patients with pulmonary disease and 229 healthy subjects. The observed levels of CEA, NSE, CYFRA-21-1, CA-125, and CA-19.9 in patients with pathologically confirmed lung cancer were significantly higher than those in patients with benign pulmonary disease or control subjects. Adenocarcinoma, squamous cell carcinoma, and small cell carcinoma of the lung were associated with the highest observed levels of CA-125, CYFRA-21-1, and NSE, respectively. Combining biomarkers successfully led to the diagnosis of lung cancer. CEA + NSE + CA-125 showed the highest sensitivity for small cell carcinoma, at 83.33%, whereas CEA + NSE + CYFRA-21-1 + CA-125 showed 94.11% sensitivity for squamous cell carcinoma. The combination of 6 biomarkers, namely, CEA + NSE + CYFRA-21-1 + CA-125 + ferritin + CA-19.9, showed 80.49% sensitivity for adenocarcinoma. Combining biomarkers significantly aided in the diagnosis of lung cancer. However, this increased sensitivity on combination was accompanied by a decreased specificity for lung cancer subtypes. Combining biomarkers appropriately increases their sensitivity and helps with the diagnosis of lung cancer. PMID- 22668015 TI - Epidermal growth factor receptor (EGFR) expression and mutations in the EGFR signaling pathway in correlation with anti-EGFR therapy in head and neck squamous cell carcinomas. AB - Epidermal growth factor receptor (EGFR) is an important therapeutic target and a poor prognosis factor in head and neck squamous cell carcinoma (HNSCC). The aim of the study was to analyze EGFR expression and KRAS and EGFR mutational status and to correlate it with treatment response to anti-EGFR therapy combined with radiotherapy in 29 patients with advanced head and neck squamous cell carcinomas (HNSCC).EGFR gene expression normalized to GAPDH and EGFR variant type III (EGFRvIII) was detected in tumor tissue using real time reverse transcription PCR. The mutational status of the EGFR and KRAS genes was investigated by real time PCR with sequence specific primers.Gene expression median values were 3.1x10(8) GAPDH gene copies per ug of RNA, and 8x10(6) EGFR gene copies per ug of RNA. The median EGFR/GADPH ratio reached 0.14. Patients, who achieved complete response after Cetuximab combined with radiotherapy, had significantly higher expression of the EGFR gene in tumors than patients with partial remission or patient without treatment response. An EGFRvIII mutation was found in 20.7 % of patients and no association was found between this mutation and treatment response. 27 patients (93.1 %) had an EGFR gene wild type tumor, and deletion in exon 19 was found in two patients with a poor clinical outcome. Most of the patients (82.8%) had a KRAS wild type tumor; a p.Gly12Cys was found in three patients and a p.Gly12Val mutation in one. Presence of a p.Gly12Val mutation in the KRAS gene was associated with an absence of response to treatment. CONCLUSION: Our data suggest that KRAS mutation (p.Gly12Val) and somatic EGFR mutation located in exon 19 may contribute to the limited clinical response to therapy with cetuximab + radiotherapy. Higher EGFR gene expression serves as an independent indicator of good clinical response to EGFR-targeted therapy + radiotherapy. PMID- 22668016 TI - Immunohistochemical and histomorphological analysis of rat mammary tumors after simvastatin treatment. AB - The results of experimental studies have indicated the pleiotropic effects of statins in organism, e.g. the influence on cell cycle, apoptosis or angiogenesis. In this study, the effects of simvastatin on selected parameters of apoptosis and proliferation in chemocarcinogen-induced mammary tumorigenesis in female rats were determined. Simvastatin was administered dietary at a dose of 18 mg/kg and highly effective dose of 180 mg/kg the entire experiment (18 weeks). At autopsy mammary tumors were removed and prepared for immunohistochemical and histomorphological analysis. In treated animals (simvastatin 180 mg/kg), significant decrease by 12% in Bcl-2 protein expression and non-significant decrease by 27% of Ki67 protein expression in tumor cells compared to tumor cells in control animals were observed after semiquantitative evaluation. Morphometrical analysis has shown significant proapototic shift in Bcl-2/Bax ratio in tumor cells. In high grade control carcinoma cells, the expression of Ki67 increased by 37% (non-significantly) in comparison with control low grade carcinomas. A histomorphological analysis of malignant tumors has revealed a shift from high grade to low grade carcinomas after simvastatin treatment. The noticeable decrease of mammary tumor frequency and incidence in rats after simvastatin treatment was accompanied with antiapoptotic Blc-2 protein decrease and proapoptotic Bax protein increase in this experiment. PMID- 22668017 TI - SKLB1002, a novel inhibitor of VEGF receptor 2 signaling, induces vascular normalization to improve systemically administered chemotherapy efficacy. AB - Vascular endothelial growth factor receptor (VEGFR) or vascular endothelial growth factor (VEGF) inhibitors have shown only modest clinical activity for most tumor types when used as single agents. However, present evidence indicates that these antiangiogenic drugs can cause transient "normalization" of the tumor vasculature, thereby improving the delivery of systemic chemotherapy. We examined temporal changes in tumor vascular function in response to the novel VEGFR2 inhibitor, SKLB1002. Established tumor-bearing animals were evaluated at serial time points for treatment-associated changes in tumor vascular architecture and function. As a result, blocking VEGF signaling by SKLB1002 produced a morphologically and functionally "normalized" vascular network. Consistent with our observations, a 2.2 fold increase in intratumoral doxorubicin levels was determined with SKLB1002 pretreatment compared with administration of doxorubicin alone. Finally, combined SKLB1002 and doxorubicin exhibited significant antitumor (49% of control size) and antimetastatic effects (12% of control metastatic nodules) in vivo. Our results showed SKLB1002 induced vascular normalization and enhanced anticancer drug delivery, which were associated with the observed synergistic effect in vivo. PMID- 22668018 TI - Lack of association between MDM2 SNP309 and TP53 Arg72Pro polymorphisms with clinical outcomes in myelodysplastic syndrome. AB - MDM2/p53 pathway plays an important role in the control of apoptotic and proliferation mechanisms, and alterations in this pathway have been described in myelodysplastic syndromes (MDS). We investigated the frequency of MDM2 SNP309, TP53 Arg72Pro polymorphisms in de novo MDS and the association of these polymorphisms with clinical characteristics. Our results showed that the frequencies of genotypes for MDM2 SNP309 and TP53 Arg72Pro did not differ between MDS and healthy controls and that these polymorphisms were not associated with clinical and laboratory parameters, disease progression and overall survival, suggesting that MDM2 and TP53 polymorphisms are not involved in risk for MDS, or in the clinical and laboratory characteristics of the disease. PMID- 22668019 TI - PET/CT significance for planning radiotherapy of head and neck cancer. AB - The combination of positron emission tomography and computed tomography (PET/CT) offers metabolic mapping in addition to anatomic information of the primary lesion, nodal and distant metastases in patients with head and neck tumors, and may be therefore beneficial for radiotherapy planning. The aim of our study was to evaluate benefits of combined PET and CT imaging for staging and target volume delineation in this group of patients.Fifty three patients (40 men and 13 women) with confirmed advanced, inoperable or non-radically operated head and neck cancer were assessed based on the results of PET/CT as well as standard diagnostic examinations. All patients were subsequently treated with intensity modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) of 6 MV X rays. There was an agreement between the standard examinations results and results of PET/CT in 30 cases. In 23 cases there was disagreement either in tumor size, nodal involvement or presence of distant metastases. Results of the tumor size assessment differed significantly in 5 cases. There was no agreement found in nodal involvement in 10 cases. The cancer confirmed by standard examination was not found by PET/CT in 2 cases; 3 PET/CT positive findings were not confirmed by standard examinations. In 3 patients PET-CT revealed new distant metastatic disease. Based on PET/CT assessment we changed treatment strategy and applied potentially curative dose of radiotherapy to previously undiscovered regions in 9 patients. We decided to change the treatment intent in 3 cases and only palliative treatment was applied. Based on our experience and the literature review, PET/CT may be considerable contribution to the standard diagnostic procedures in approximately one third of cases. PMID- 22668020 TI - Knockdown of RhoGDIalpha induces apoptosis and increases lung cancer cell chemosensitivity to paclitaxel. AB - This study aimed to investigate the effects of RhoGDIalpha knockdown on apoptosis and the chemosensitivity of lung cancer cells to paclitaxel. The signaling proteins involved were also assessed. RhoGDIalpha expression was assessed by RT PCR, Western blotting and immunohistochemistry. Apoptosis was determined by flow cytometric assessment, and cell viability was measured with the MTT assay. Phosphorylation levels of signaling proteins, ERK, JNK, Akt, Bad and IkappaBalpha were tested by Western blotting and immunohistochemistry. Positivity for RhoGDIalpha in lung cancer tissues was significantly higher than in paracancerous tissues. Downregulation of RhoGDIalpha was associated with significantly increased apoptosis and repressed cell viability. This effect could be due to the consequent upregulation of p-JNK, as well as decreased levels of p-ERK, p-Bad and p-IkappaBalpha. Knockdown of RhoGDIalpha strengthened the effect on apoptosis and inhibition of cell viability induced by paclitaxel treatment. This chemosensitization effect could be a result of the intensification of pro apoptotic JNK activation, and repression of anti-apoptotic p-ERK, p-Bad and p IkappaBalpha expression stimulated by paclitaxel. In summary, our study indicated that RhoGDIalpha could be a promising therapeutic target, and the combination of RhoGDIalpha siRNA and paclitaxel might be a valuable potential therapy for lung cancer treatment. PMID- 22668021 TI - Tandem autologous stem cell transplantation in multiple myeloma after high-dose chemotherapy with two separate collections: single institution experience. AB - Presented is a retrospective analysis of multiple myeloma patients transplanted at our institution between November 1993 and August 2007. The objective of this analysis was to assess the feasibility and toxicity of tandem autologous stem cell transplantation (T-ASCT) when stem cells were harvested before first and before second transplantation separately. A total of 90 patients transplanted in our center were analyzed, of whom 43 patients were in tandem transplantation group.The overall response rate (ORR) was 83.7% and 95.1%, estimated five-year overall survival (OS) was 40.1% and 60.0%, probability of five-year event-free survival (EFS) was 18.2% and 25.6%, transplant related mortality (TRM) was 6.3% and 4.6% in the single and tandem transplant group, respectively. In multivariable analysis of all 90 patients, tandem transplantation and ORR attained after induction therapy were favourable prognostic factors for OS (p=0.024 and p=0.002) and EFS (p=0.036 and p=0.008), respectively. In conclusion, tandem transplantation with two separate stem cell harvests, performed separately before the each transplantation, is feasible in majority of patients with acceptable toxicity. PMID- 22668022 TI - Lung cancer in a Czech cohort exposed to radon in dwellings--50 years of follow up. AB - The presented study reports lung cancer mortality in a cohort of 11 842 subjects exposed to high levels of radon covering the period 1961-2010. Exposure estimates were based on one year measurements of radon progeny in most houses of the study area (72%), missing values in the studied area were replaced by measurements in proxy houses (9%) and exposures outside the area (19%) were based on country radon mapping. Mean concentration of 448 Bq m(-3) in the study is higher than the country mean by a factor of 5. By 2010, a total of 293 lung cancers were observed. The risk is significantly related to cumulated exposure with ERR/100Bq m(-3) 0.11 (90%CI: 0.04 - 0.25). This value is consistent with the risk coefficients in other indoor studies and also with the risks observed among uranium miners. The present follow-up demonstrated that increased incidence of lung cancer depends mainly on exposure from previous 5-19 years. The relative risk of lung cancer in the present study derived from this model is 1.53 (90%CI: 1.39 - 1.69). PMID- 22668023 TI - The relationship of multifocality and tumor burden with various tumor characteristics and survival in early breast cancer. AB - The presence of multifocality and the aggregate tumor size were retrospectively analysed in a database of 1071 operated breast cancers. Around a quarter of all these cancers involved multiple foci, while a tenth of the total demonstrated more than one invasive focus. Although the multifocal cancers were smaller and more often screen-detected than the unifocal cancers, their aggregate tumor size was larger, and they more frequently displayed casting-type calcifications in the mammogram and HER2 positivity. Lobular histology favoured larger tumor burden. The invasive multifocal cancers were more commonly lymph node-positive than the other tumors. In a subgroup of 584 patients with a median follow-up time of 5 years, the larger size of the invasive tumor, the presence of LVI or lymph node involvement, HER2 positivity and triple negativity were associated with a poorer RFS and OS, while the outcome of screen-detected tumors was superior to that of non-screen-detected or interval cancers. A large tumor size, lymph node positivity and HER2 positive or triple negative phenotypes were independent determinants of a poorer survival rate. PMID- 22668024 TI - COX-2 expression in fibroblast aggregates as a functional indicator for the anti inflammatory activity of leukemia patients' bone marrow-derived hematopoietic cells. AB - Reciprocal communication between hematopoietic cells and their surrounding bone marrow stroma is crucial for normal progression of hematopoiesis. This complex network of cell-to-cell signals in the microenvironment involves both cell contact-mediated and paracrine cues. In hematological malignancies the intricate balance is, however, disrupted to support cancer progression. In order to detect altered microenvironmental reactivity of a hematopoietic cell sample, cellular functional assays can be designed to measure the cells' capacity to modulate stromal stress reactions, such as inflammation.Recently, we showed that human leukemic cell lines of monocytic origin can actively participate in modulation of stromal inflammation. In order to further functionally evaluate the hematopoietic cells' capacity to modulate stromal inflammation, we utilized an in vitro model of nemosis-induced inflammation of fibroblasts in a three-dimensional culture setting. This process of stromal inflammation in fibroblast aggregates is consistent, requires both cell-contact and paracrine signals, and can be produced on a large scale to support dose-dependent analyses. To extend our previous observations, we evaluated the effect of a wide panel of leukemia cell lines on cyclooxygenase- 2 induction in fibroblast aggregates in co-culture. We also assessed the feasibility of the model to support clinical functional testing by utilizing the hematopoietic fraction of leukemia patients' bone marrow aspirates after immunophenotyping. Our results suggest that the stromal inflammation modulating activity of these samples is differently modulated in cancer and in normal bone marrow. Moreover, differences in the samples' anti-inflammatory activity may reflect disease state. PMID- 22668025 TI - The intensity of internalization and cytotoxicity of superparamagnetic iron oxide nanoparticles with different surface modifications in human tumor and diploid lung cells. AB - The human lung adenocarcinoma epithelial (A549) cells and the human embryo lung (HEL 12469) cells were used to investigate the uptake and cytotoxicity of magnetite nanoparticles (MNPs) with different chemically modified surfaces. MNPs uptake was an energy-dependent process substantially affected by the serum concentration in the culture medium. Internalized MNPs localized in vesicle-bound aggregates were observed in the cytoplasm, none in the nucleus or in mitochondria. All MNPs induced a dose- and time-dependent increase in cytotoxicity in both human lung cell lines. The cytotoxicity of MNPs increased proportionally with the particle size. Since the cytotoxicity of MNPs was nearly identical when the doses were equalized based on particle surface area, we suppose that the particle surface area rather than the surface modifications per se underlay the cytotoxicity of MNPs. In general, higher internalized amount of MNPs was found in HEL 12469 cells compared with A549 cells. Accordingly, the viability of the human embryo lung cells was reduced more substantially than that of the adenocarcinoma lung cells. The weak MNPs uptake into A549 cells might be of biomedical relevance in cases where MNPs should be used as nanocarriers for targeted drug delivery in tumor tissue derived from alveolar epithelial cells. PMID- 22668026 TI - Effect of estradiol on the expression of renal sodium transporters in rats. AB - BACKGROUND: Although estradiol has been thought to perform an important role in blood pressure regulation, the effects of estradiol on the expression of renal sodium transporters are not fully understood. METHODS: Female Sprague-Dawley rats were treated with 17beta-estradiol or vehicle for 10 days after ovariectomy, and after both ovariectomy and adrenalectomy to eliminate the effect of aldosterone. RESULTS: In the ovariectomized (OVX) rats, estradiol decreased the abundance of the Na-K-2Cl cotransporter (NKCC2) (31.5% of control (OVX), p < 0.01), Na-Cl cotransporter (NCC) proteins (40.5% of control (OVX), p < 0.01) and alpha- and gamma-subunits of the epithelial sodium channel (ENaC) (44.7% and 11.0% of control (OVX), p < 0.01). Estradiol also reduced plasma aldosterone levels (OVX + 17beta-estradiol vs. OVX, 116.3 +/- 44.4 vs. 184.2 +/- 33.4 pmol/l, p < 0.05) and systolic blood pressure (OVX + 17beta-estradiol vs. OVX, 115 +/- 4 vs. 132 +/- 2 mmHg, p < 0.05). In rats having undergone adrenalectomy and ovariectomy, estradiol did not reduce systolic blood pressure, or the expression of sodium transporters. CONCLUSION: Estradiol decreased systolic blood pressure, plasma aldosterone levels, and the expression of renal sodium transporters. After aldosterone was eliminated, estradiol did not affect blood pressure or the expression of sodium transporters, which indicates that the effect of estradiol on the renal sodium transporters is at least partly influenced by aldosterone. PMID- 22668027 TI - New twists on the perovskite theme: crystal structures of the elusive phases R and S of NaNbO3. AB - The crystal structure of NaNbO(3) has been studied in detail in the temperature regime 360 < T < 520 degrees C using a combination of high-resolution neutron and synchrotron X-ray powder diffraction, supported by first-principles calculations. A systematic symmetry-mode analysis is used to determine the presence of the key active distortion modes that, in turn, provides a small and an unambiguous set of trial structural models. A unique model for Phase S (480 < T < 510 degrees C) is elucidated, having a 2 * 2 * 4 superlattice of the aristotype perovskite structure, space group Pmmn. This unusual and unique structure features a novel example of a compound octahedral tilt system in a perovskite. Two possible structural models for Phase R (370 < T < 470 degrees C) are determined, each having a 2 * 2 * 6 superlattice and differing only in the nature of the complex tilt system along the 'long' axis. It is impossible to identify a definitive model from the present study, although reasons for preferring one over the other are discussed. Some of the possible pitfalls in determining such complex, pseudosymmetric crystal structures from powder diffraction data are also highlighted. PMID- 22668028 TI - Vg instruments inc. PMID- 22668029 TI - Ert. PMID- 22668030 TI - Rockwell international. PMID- 22668031 TI - Guest editorial. PMID- 22668032 TI - Fermentation technology. PMID- 22668033 TI - Chemical & engineering news. PMID- 22668035 TI - An expanding experience... PMID- 22668034 TI - History of acid rain. PMID- 22668037 TI - International. PMID- 22668036 TI - Mead CompuChem(r). PMID- 22668038 TI - Washington. PMID- 22668040 TI - State. PMID- 22668039 TI - Technology. PMID- 22668042 TI - Industry. PMID- 22668041 TI - Science. PMID- 22668044 TI - Trends in nuclear power. PMID- 22668043 TI - Sunohio. PMID- 22668045 TI - Fill a staff position on capitol hill. PMID- 22668048 TI - Pesticide residues and exposure. PMID- 22668047 TI - Fixed-film biological processes. PMID- 22668049 TI - The Council on Environmental Quality: an enviable record in jeopardy. PMID- 22668050 TI - A case history of the North Dakota PSD program. PMID- 22668051 TI - Research appliance company. PMID- 22668052 TI - Sampling and analysis of mercury and its compounds in the atmosphere. PMID- 22668053 TI - Statistical distributions of air pollutant concentrations. PMID- 22668054 TI - Myron L company. PMID- 22668055 TI - Sensorex. PMID- 22668056 TI - Spill detector. PMID- 22668057 TI - Environmental science & technology. PMID- 22668059 TI - professional consulting services directory. PMID- 22668062 TI - International. PMID- 22668060 TI - Classified section * positions open. PMID- 22668065 TI - Curcumin and neurodegenerative diseases: a perspective. AB - INTRODUCTION: Curcumin, a dietary polyphenol found in the curry spice turmeric, possesses potent antioxidant and anti-inflammatory properties and an ability to modulate multiple targets implicated in the pathogenesis of chronic illness. Curcumin has shown therapeutic potential for neurodegenerative diseases including Alzheimer's disease (AD) and Parkinson's disease (PD). AREAS COVERED: This article highlights the background and epidemiological evidence of curcumin's health benefits and its pharmacodynamic and pharmacokinetic profile. Curcumin's ability to counteract oxidative stress and inflammation and its capacity to modulate several molecular targets is reviewed. We highlight the neuroprotective properties of curcumin including pre-clinical evidence for its pharmacological effects in experimental models of AD and PD. The bioavailability and safety of curcumin, the development of semi-synthetic curcuminoids as well as novel formulations of curcumin are addressed. EXPERT OPINION: Curcumin possesses therapeutic potential in the amelioration of a host of neurodegenerative ailments as evidenced by its antioxidant, anti-inflammatory and anti-protein aggregation effects. However, issues such as limited bioavailability and a paucity of clinical studies examining its therapeutic effectiveness in illnesses such as AD and PD currently limit its therapeutic outreach. Considerable effort will be required to adapt curcumin as a neuroprotective agent to be used in the treatment of AD, PD and other neurodegenerative diseases. PMID- 22668066 TI - Theoretical and experimental studies of the spin trapping of inorganic radicals by 5,5-dimethyl-1-pyrroline N-oxide (DMPO). 3. Sulfur dioxide, sulfite, and sulfate radical anions. AB - Radical forms of sulfur dioxide (SO(2)), sulfite (SO(3)(2-)), sulfate (SO(4)(2 )), and their conjugate acids are known to be generated in vivo through various chemical and biochemical pathways. Oxides of sulfur are environmentally pervasive compounds and are associated with a number of health problems. There is growing evidence that their toxicity may be mediated by their radical forms. Electron paramagnetic resonance (EPR) spin trapping using the commonly used spin trap, 5,5 dimethyl-1-pyrroline N-oxide (DMPO), has been employed in the detection of SO(3)(*-) and SO(4)(*-). The thermochemistries of SO(2)(*-), SO(3)(*-), SO(4)(* ), and their respective conjugate acids addition to DMPO were predicted using density functional theory (DFT) at the PCM/B3LYP/6-31+G**//B3LYP/6-31G* level. No spin adduct was observed for SO(2)(*-) by EPR, but an S-centered adduct was observed for SO(3)(*-)and an O-centered adduct for SO(4)(*-). Determination of adducts as S- or O-centered was made via comparison based on qualitative trends of experimental hfcc's with theoretical values. The thermodynamics of the nonradical addition of SO(3)(2-) and HSO(3)(-) to DMPO followed by conversion to the corresponding radical adduct via the Forrester-Hepburn mechanism was also calculated. Adduct acidities and decomposition pathways were investigated as well, including an EPR experiment using H(2)(17)O to determine the site of hydrolysis of O-centered adducts. The mode of radical addition to DMPO is predicted to be governed by several factors, including spin population density, and geometries stabilized by hydrogen bonds. The thermodynamic data supports evidence for the radical addition pathway over the nucleophilic addition mechanism. PMID- 22668067 TI - Pharmacokinetic study of saxagliptin in healthy Chinese subjects. AB - BACKGROUND AND OBJECTIVES: The pharmacokinetics of some medications may be affected by differences in race and ethnicity, which can lead to suboptimal outcomes. The present study was conducted to assess the single- and multiple-dose pharmacokinetics of saxagliptin in healthy Chinese subjects living in China. METHODS: This was an open-label, 9-day study conducted at the Drug Clinical Trial Center, Peking University Third Hospital, Beijing, China. Sixteen healthy Chinese subjects of both sexes between 21 and 33 years of age were administered saxagliptin 5 mg orally on day 1, then once daily on days 3-7. Pharmacokinetic variables for saxagliptin (primary outcome) and its active metabolite, 5-hydroxy saxagliptin (secondary outcome), after single and multiple oral doses of saxagliptin were assessed. Safety was also assessed. RESULTS: Saxagliptin was absorbed rapidly (median time to reach maximum concentration [t(max)]: 0.5 and 1 hour on days 1 and 7, respectively), and its pharmacologically active metabolite, 5-hydroxy saxagliptin, appeared in plasma (median t(max): 1.0 and 1.5 hours, respectively). Plasma exposure to 5-hydroxy saxagliptin was approximately 2- to 3 fold higher than exposure to saxagliptin. Plasma concentration-time profiles for saxagliptin and 5-hydroxy saxagliptin were similar on days 1 and 7, with no evidence of drug accumulation on repeated dosing. The elimination half-lives (t(1/2)) for saxagliptin and 5-hydroxy saxagliptin were approximately 3 and 4 hours, respectively, with renal excretion as the primary route of elimination. After single and multiple dosing, 54.48% and 52.60%, respectively, of the administered saxagliptin dose was recovered in urine as unchanged drug or 5 hydroxy saxagliptin. Saxagliptin was generally well tolerated. Six (37.5%) subjects experienced an adverse event (AE). All AEs were mild in intensity and judged by the investigator as not related to the study medication. There were no deaths, serious AEs, discontinuations due to AEs, or other clinically significant AEs during this study. CONCLUSION: Saxagliptin 5 mg (single dose and once-daily doses for 5 days) was generally well tolerated; the pharmacokinetics of saxagliptin and 5-hydroxy saxagliptin in healthy Chinese subjects were consistent with previous assessments in the saxagliptin clinical development program. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00770302. PMID- 22668068 TI - Carryover of maduramicin from feed containing cross-contamination levels into eggs of laying hens. AB - Maduramicin is a coccidiostat authorized as feed additive in the European Union for chickens and turkeys for fattening but not for laying hens, considering the risk of residues in eggs. The unavoidable cross-contamination of non-target feed with coccidiostats is regulated by Commission Directive 2009/8/EC and resulting carry-over in food by Commission Regulation (EC) No. 124/2009. To verify the compliance of the maximum levels for maduramicin in feed (50 MUg/kg) and eggs (2 MUg/kg), the carry-over from feed into eggs was investigated. Diets containing 10, 30, and 50 MUg of maduramicin/kg of feed were fed to laying hens. Feed, egg white, and yolk were analyzed by LC-MS/MS. Maduramicin residues were only detected in in egg yolk. Feeding the 10 MUg/kg maduramicin diet resulted in maduramicin concentrations up to 2.5 MUg/kg in whole eggs, already exceeding the maximum level. A carry-over rate of 8% maduramicin from feed into eggs was calculated. PMID- 22668069 TI - Mitochondrial pathways, permeability transition pore, and redox signaling in cardioprotection: therapeutic implications. AB - Reperfusion therapy is the indispensable treatment of acute myocardial infarction (AMI) and must be applied as soon as possible to attenuate the ischemic insult. However, reperfusion is responsible for additional myocardial damage likely involving opening of the mitochondrial permeability transition pore (mPTP). A great part of reperfusion injury occurs during the first minute of reperfusion. The prolonged opening of mPTP is considered one of the endpoints of the cascade to myocardial damage, causing loss of cardiomyocyte function and viability. Opening of mPTP and the consequent oxidative stress due to reactive oxygen and nitrogen species (ROS/RNS) are considered among the major mechanisms of mitochondrial and myocardial dysfunction. Kinases and mitochondrial components constitute an intricate network of signaling molecules and mitochondrial proteins, which interact in response to stressors. Cardioprotective pathways are activated by stimuli such as preconditioning and postconditioning (PostC), obtained with brief intermittent ischemia or with pharmacological agents, which drastically reduce the lethal ischemia/reperfusion injury. The protective pathways converging on mitochondria may preserve their function. Protection involves kinases, adenosine triphosphate-dependent potassium channels, ROS signaling, and the mPTP modulation. Some clinical studies using ischemic PostC during angioplasty support its protective effects, and an interesting alternative is pharmacological PostC. In fact, the mPTP desensitizer, cyclosporine A, has been shown to induce appreciable protections in AMI patients. Several factors and comorbidities that might interfere with cardioprotective signaling are considered. Hence, treatments adapted to the characteristics of the patient (i.e., phenotype oriented) might be feasible in the future. PMID- 22668070 TI - Nasal obstruction and rhinorrhea reflect nonspecific nasal hyper-reactivity as evaluated by cold dry air provocation. AB - CONCLUSION: Nasal obstruction, rhinorrhea, and the amount of rhinorrhea that confidently reflect the parasympathetic stimulation can be used to more precisely predict nonspecific nasal hyper-reactivity (NHR). OBJECTIVE: We aimed to identify factors that confidently reflected the presence and the degree of NHR, measured by cold dry air (CDA) provocation and acoustic rhinometry. METHODS: A total of 156 patients with allergic or non-allergic rhinitis were classified into three groups according to the decrease of minimal cross-sectional area (MCA) after CDA provocation (group A: n = 40, MCA decrease >60%; group B: n = 29, MCA decrease 30 60%; group C: n = 87, MCA decrease <29%). Symptom scores using the visual analog scale (VAS) were obtained before and after CDA provocation. Changes of VAS were compared between groups. The amount of rhinorrhea was measured after CDA provocation. RESULTS: VAS scores for nasal obstruction, rhinorrhea, and sneezing were significantly higher in groups A and B than in group C before and after CDA provocation. Change of nasal obstruction and rhinorrhea was significantly larger in group A compared with group B or C. There were also significant differences in the amount of rhinorrhea between groups. All these parameters significantly correlated with the change of MCA values after CDA provocation. PMID- 22668071 TI - Food-drug interactions: effect of capsaicin on the pharmacokinetics of galantamine in rats. AB - Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide, CAP) is a naturally occurring alkaloid extracted from the fruit of Capsicum plant family. It represents an important ingredient in spicy foods consumed throughout the world. However, little is known about the metabolic interactions between CAP and clinically used drugs. This study attempted to investigate the effect of CAP on the pharmacokinetics of galantamine, a competitive and reversible cholinesterase inhibitor. CAP, dexamethasone or sodium salt of carboxymethyl cellulose (CMC-Na) was given to rats for seven consecutive days and on the seventh day galantamine (10 mg/kg) was administered orally. Dexamethasone was used as a CYP inducer and CMC-Na was used as a vehicle. The results showed that the pretreatment of rats with CAP resulted in a decrease in the AUC(0-infinity) of galantamine of about 49.70% (p < 0.01) compared with the control group. After oral administration of galantamine (10 mg/kg), the apparent oral clearance of galantamine was raised by 2.05-fold by pretreatment with CAP (p < 0.05). These results demonstrate that the chronic ingestion of high doses of CAP will decrease the bioavailability of galantamine to a significant extent in rats. PMID- 22668072 TI - Nickel-catalyzed coupling reactions of alkyl electrophiles, including unactivated tertiary halides, to generate carbon-boron bonds. AB - Through the use of a catalyst formed in situ from NiBr(2).diglyme and a pybox ligand (both of which are commercially available), we have achieved our first examples of coupling reactions of unactivated tertiary alkyl electrophiles, as well as our first success with nickel-catalyzed couplings that generate bonds other than C-C bonds. Specifically, we have determined that this catalyst accomplishes Miyaura-type borylations of unactivated tertiary, secondary, and primary alkyl halides with diboron reagents to furnish alkylboronates, a family of compounds with substantial (and expanding) utility, under mild conditions; indeed, the umpolung borylation of a tertiary alkyl bromide can be achieved at a temperature as low as -10 degrees C. The method exhibits good functional-group compatibility and is regiospecific, both of which can be issues with traditional approaches to the synthesis of alkylboronates. In contrast to seemingly related nickel-catalyzed C-C bond-forming processes, tertiary halides are more reactive than secondary or primary halides in this nickel-catalyzed C-B bond-forming reaction; this divergence is particularly noteworthy in view of the likelihood that both transformations follow an inner-sphere electron-transfer pathway for oxidative addition. PMID- 22668074 TI - A new approach to the synthesis of peptidomimetic renin inhibitors: palladium catalyzed asymmetric allylation of acyclic alkyl aryl ketones. AB - A new approach to the synthesis of Tekturna, a recently marketed drug for hypertension, takes advantage of a modified protocol of the Stoltz palladium catalyzed asymmetric allylation with a t-BuPHOX ligand for the synthesis of allylated acyclic alkyl aryl ketones. The method led to an alpha-isopropyl alpha allyl aryl ketone in 90% yield and 88 to 91% ee, which was used in the synthesis of an advanced intermediate toward Tekturna. A beneficial effect of protic additives, such as BHT (2,6-di-tert-butyl-p-cresol), on the time and enantioselectivity of the reaction was discovered. PMID- 22668073 TI - Homozygous M34T mutation of the GJB2 gene associates with an autosomal recessive nonsyndromic sensorineural hearing impairment in Finnish families. AB - CONCLUSION: The genetic and audiological data support the hypothesis that the p.M34T is a pathogenic mutation in the Finnish population. The p.M34T mutation displays an autosomal recessive pattern of inheritance and is associated with mild to moderate nonsyndromic sensorineural hearing impairment (SNHI) in the homozygous state. The audiograms often display a hearing impairment notch at 2-4 kHz in young patients, which may aid in the early diagnosis. OBJECTIVES: The aim of the study was to assess whether the p.M34T mutation in the GJB2 gene may associate with nonsyndromic SNHI. METHODS: We systematically reviewed the families with children diagnosed with nonsyndromic SNHI caused by a homozygous p.M34T mutation at the Kuopio and Oulu University Hospital Clinics. The children were re-examined and audiological and genetic data were obtained from their parents and healthy siblings to study genotype-phenotype correlation. RESULTS: We describe 11 patients from 6 families including 5 sibling pairs from 6 to 23 years of age with homozygous p.M34T genotype all having mild nonsyndromic SNHI. In addition, we found three patients with compound p.M34T mutation also exhibiting mild to moderate SNHI. PMID- 22668075 TI - A heterometallic (Ni(II)-Cu(II)) decanuclear cluster containing two distorted cubane-like pentanuclear cores: synthesis, structure, and magnetic properties. AB - A new heterometallic Ni(II)-Cu(II) decanuclear cluster, {[Ni(4)Cu(6)(MU OH(2))(2)(dpkO(2))(8)(OAc)(4)(H(2)O)(4)].2CH(3)OH.17H(2)O} (1), has been synthesized by self-assembly of the constituent metal ions and the precursor di-2 pyridylketone (dpk) of multinucleating ligand dpkO(2)(2-) and is structurally characterized. The cluster 1 is formed by the union of two symmetry-related distorted cubane-like pentanuclear cores. A magnetic study of 1 reveals strong antiferromagnetic interactions operating through the Ni-O-Ni pathway, which is independent of the assumption D = 0 or D ? 0. The pentanuclear cores are ferromagnetically coupled, as supported by density functional theory calculations. PMID- 22668076 TI - Clinical manifestation and risk factors of children with cleft palate receiving repeated ventilating tube insertions for treatment of recurrent otitis media with effusion. AB - CONCLUSION: From this study, we suggest that male gender and complete type of cleft palate contribute to the recurrence of otitis media with effusion (OME) in the patients with cleft palate. OBJECTIVES: It is well known that children with cleft palate have a high prevalence of OME due to anatomic dysfunction of the eustachian tube. Our goal was to determine clinical manifestations and risk factors for children with cleft palate who received additional ventilating tube insertions after initial tube insertion during palatoplasty. METHODS: We retrospectively reviewed the medical and operation records of 213 patients who received ventilating tube insertion during palatoplasty from January 1993 to June 2006. The single-VT group (n = 140) included patients who had one ventilating tube insertion only, and the repeated-VT group (n = 73) included patients who received ventilating tube insertion repeatedly because of recurring chronic OME. We analyzed age, sex, types of cleft palate, preoperative tympanogram, characteristics of discharge during myringotomy, and duration of first ventilating tube in situ. RESULTS: There were significant differences between the single- and repeated-VT groups in the rate of male patients (43.6 vs 72.6%), the rate of complete cleft palate (30.0 vs 61.6%) and incomplete cleft palate (61.4 vs 26.0%), the rate of preoperative type A tympanogram (30.0 vs 13.7%) and type B tympanogram (57.1 vs 75.3%), the proportion of discharge during myringotomy (72.1 vs 86.3%), and the mean indwelling period of the first ventilating tube (12.7 +/- 9.6 vs 10.5 +/- 6.5 months). In addition, sex and type of cleft palate were proved to affect the repetition of VT independently. However, when we performed multivariate analysis, only complete type of cleft palate and male gender showed significant differences between single- and repeated-VT groups. PMID- 22668077 TI - Microdosimetry of low-energy electrons. AB - PURPOSE: To investigate differences in energy depositions and microdosimetric parameters of low-energy electrons in liquid and gaseous water using Monte Carlo track structure simulations. MATERIALS AND METHODS: KURBUC-liq (Kyushu University and Radiobiology Unit Code for liquid water) was used for simulating electron tracks in liquid water. The inelastic scattering cross sections of liquid water were obtained from the dielectric response model of Emfietzoglou et al. (Radiation Research 2005;164:202-211). Frequencies of energy deposited in nanometre-size cylindrical targets per unit absorbed dose and associated lineal energies were calculated for 100-5000 eV monoenergetic electrons and the electron spectrum of carbon K edge X-rays. The results for liquid water were compared with those for water vapour. RESULTS: Regardless of electron energy, there is a limit how much energy electron tracks can deposit in a target. Phase effects on the frequencies of energy depositions are largely visible for the targets with diameters and heights smaller than 30 nm. For the target of 2.3 nm by 2.3 nm (similar to dimension of DNA segments), the calculated frequency- and dose-mean lineal energies for liquid water are up to 40% smaller than those for water vapour. The corresponding difference is less than 12% for the targets with diameters >= 30 nm. CONCLUSIONS: Condensed-phase effects are non-negligible for microdosimetry of low-energy electrons for targets with sizes smaller than a few tens of nanometres, similar to dimensions of DNA molecular structures and nucleosomes. PMID- 22668078 TI - Patupilone and ixabepilone: the effect of a point structural change on the exo endo conformational profile. AB - The natural product patupilone (epothilone B) and its synthetic aza-analogue, ixabepilone, are effective agents against a broad range of human cancers. A detailed conformational analysis was conducted on the basis of single-point MP2 energy calculations for density functional theory (DFT) geometries at the MP2/6 31+G(d,p)//B3LYP/6-31+G(d,p) level. In a vacuum, patupilone exclusively adopts compact exo conformations due to short, near-linear hydrogen bonding between the 3-hydroxyl group and the side-chain thiazole. In contrast, ixabepilone can be described as a competitive mixture of exo and endo conformers with a large population of the above-mentioned compact exo conformations. The stability of the endo form is consistent with the cooperativity of hydrogen bonds. The relative energies of some patupilone and ixabepilone conformers were found to be sensitive to solvent effects within the integral equation formalism polarizable continuum model (IEF-PCM). This study contributes to a better understanding of the important structural features of patupilone and ixabepilone. This conformational analysis lends support to previous observations concerning their different pharmaceutical profiles. PMID- 22668079 TI - Factors associated with serum polybrominated diphenyl ether (PBDE) levels among school-age children in the CHAMACOS cohort. AB - Polybrominated diphenyl ethers (PBDEs) are a class of flame retardants historically used in textiles, furniture, and electronic products. Recent studies have documented widespread PBDE exposure to humans, with higher levels measured in children than adults. We analyzed 10 tri- to hepta-BDE congener levels in blood collected from 7-year old Mexican-American children living in an agriculture community in California (n = 272). The most frequently detected PBDE congeners in child serum were BDE-47, -99, -100, and -153, all of which were measured in >99% of the children. We used multiple linear regression models to examine associations between child total PBDE levels (ng/g lipid) and determinants of exposure. Factors positively associated with higher PBDE levels in the children were total PBDE levels in maternal serum during pregnancy, duration of exclusive breastfeeding, and having no safe places to play in their neighborhood. Child BMI was inversely associated with serum PBDE levels (regression p-values <0.05). Our findings confirm that exposure to the penta-BDE mixture is ongoing, and that Mexican-American children living in California may be experiencing higher PBDE exposure from their environment compared to children sampled from the general U.S. population. Additional research is needed to assess the health impacts of these exposures. PMID- 22668080 TI - Electronic nature of substituent X governs reaction mechanism in aminolysis of 4 pyridyl X-substituted-benzoates in acetonitrile. AB - A kinetic study is reported for aminolysis of 4-pyridyl X-substituted-benzoates 5a-i. Plots of pseudo-first-order rate constants (k(obsd)) vs [amine] curve upward for the reactions of substrates possessing a strong electron-withdrawing group in the benzoyl moiety (5a-d) but are linear for the reactions of those bearing an electron-donating group (5e-i), indicating that the electronic nature of substituent X governs the reaction mechanism. The k(1)k(2)/k(-1) and k(1)k(3)/k(-1) values were calculated from the intercept and slope of the linear plots of k(obsd)/[amine] vs [amine], respectively. The Hammett plot for k(1)k(2)/k(-1) consists of two intersecting straight lines, while the Yukawa Tsuno plot exhibits an excellent linear correlation with rho(X) = 0.41 and r = 1.58, implying that the nonlinear Hammett plot is not due to a change in rate determining step but is caused by stabilization of substrates possessing an electron-donating group through resonance interactions. The small rho(X) suggests that the k(2)/k(-1) ratio is little influenced by the nature of substituent X. The Bronsted-type plots for aminolysis of 4-pyridyl 3,5-dinitrobenzoate 5a are linear with beta(nuc) = 0.98 and 0.79 for k(1)k(2)/k(-1) and k(1)k(3)/k(-1), respectively. The effect of amine basicity on the microscopic rate constants is also discussed. PMID- 22668082 TI - Proton transfer voltammetry at electrodes modified with acid thiol monolayers. AB - By combining a description of the potential profile at electrodes coated with acid thiol monolayers with a quadratic relationship between activation energy and electrode potential, a rather simple expression for proton transfer voltammograms is derived. Our electrostatic analysis shows that proton transfer can only produce narrow voltammetric peaks when the immobilized acid groups lie close to the metal substrate. Quantitative fits of experimental voltammograms obtained with an Au(111) electrode modified with a 11-mercaptoundecanoic monolayer at pH 8.5 reveal that less than 1% of the carboxylic groups in the monolayer participate in the potential induced proton transfer process and that these groups lay close to the metal surface. A preliminary analysis of the kinetic parameters suggests that the interfacial electric field facilitates an intrinsically slow proton exchange between a proton donor and acceptor pair that are not in close contact with each other at the interface. PMID- 22668081 TI - Live-cell imaging of single receptor composition using zero-mode waveguide nanostructures. AB - We exploit the optical and spatial features of subwavelength nanostructures to examine individual receptors on the plasma membrane of living cells. Receptors were sequestered in portions of the membrane projected into zero-mode waveguides. Using single-step photobleaching of green fluorescent protein incorporated into individual subunits, the resulting spatial isolation was used to measure subunit stoichiometry in alpha4beta4 and alpha4beta2 nicotinic acetylcholine and P2X2 ATP receptors. We also show that nicotine and cytisine have differential effects on alpha4beta2 stoichiometry. PMID- 22668083 TI - Rural nursing education: a photovoice perspective. AB - INTRODUCTION: For many rural Canadians nursing care is the primary and often the sole access point to health care. As such, rural nurses are an invaluable resource to the health and wellbeing of rural populations. However, due to a nursing workforce that is aging and retiring, limited resources and support, healthcare reform issues, and other factors, these rural professionals are in short supply. Because of limited opportunities to learn about rural practice settings, nursing students may be reluctant to select rural practice locations. Relevant and effective educational initiatives are needed to attract nursing students to underserved rural and remote communities so that rural people receive the health care they require. The purpose of this study was to explore the use of the innovative research approach called photovoice as an educational strategy to foster learning about and interest in rural locations and rural nursing as future practice settings. Fostering of interest in rural may help to address nursing workforce shortages in rural settings. METHODS: Thirty-eight third and fourth year nursing and health sciences students enrolled in an elective 'Rural Nursing' course used the qualitative research method photovoice to take photographs that represented challenges and facilitators of rural nursing practice. They then engaged in written reflection about their photos. Photos were to be taken in rural settings of their choice, thus fostering both urban and rural student exposure to diverse rural communities. RESULTS: One hundred forty-four photos and reflections were submitted, representing students' appreciation of diverse facilitators and challenges to rural nursing practice. Facilitators included technology, a generalist role, strong sense of community, and slower pace of life. Challenges included inadequate rural education in undergraduate nursing programs, professional isolation, safety issues, few opportunities for professional development, lack of anonymity, and insider/outsider status. Exemplar photos and reflections are provided. CONCLUSIONS: The photovoice research approach used in this rural education endeavour proved to be very useful in fostering students' exposure to, interest in, and understanding of rural settings and their influence on rural nursing practice. Photovoice is also recommended for use in rural courses other than nursing. Suggested strategies include group photovoice experience and the expansion of reflection to enhance rural health research. PMID- 22668084 TI - Efficient transfection of hepatocytes mediated by mRNA complexed to galactosylated cyclodextrins. AB - In this study, we aimed at specific targeting of polycationic amphiphilic cyclodextrins (paCDs) to HepG2 cells via the asialoglycoprotein receptor (ASGPr). The transfection efficiencies of paCDs modified with galactose moieties were evaluated. In preliminary experiments, attempts to transfect HepG2 cells with pDNA complexed with different modified paCDs resulted in very low transfection levels. In additional series of experiments, we found out that nucleic acid/cyclodextrin complexes (CDplexes) were efficiently taken up by the cells and that photochemical internalization, which facilitates release from endosomes, did not improve transfection. Further experiments showed that pDNA can be readily released from the CDplexes when exposed to negatively charged vesicles. These observations imply that the lack of transfection cannot be attributed to a lack of internalization, release of CDplexes from the endosomal compartment, or release of free pDNA from the CDplexes. This in turn suggests that the nuclear entry of the pDNA represents the main limiting factor in the transfection process. To verify that HepG2 cells were transfected with targeted CDplexes containing mRNA, which does not require entry into the nucleus for being translated. With mRNA encoding the green fluorescent protein, fractions of GFP positive cells of up to 31% were obtained. The results confirmed that the galactosylated complexes are specifically internalized via the ASGPr. PMID- 22668085 TI - Magnetic rotational spectroscopy with nanorods to probe time-dependent rheology of microdroplets. AB - In situ characterization of minute amounts of fluids that rapidly change their rheological properties is a challenge. In this paper, the rheological properties of fluids were evaluated by examining the behavior of magnetic nanorods in a rotating magnetic field. We proposed a theory describing the rotation of a magnetic nanorod in a fluid when its viscosity increases with time exponentially fast. To confirm the theory, we studied the time-dependent rheology of microdroplets of 2-hydroxyethyl-methacrylate (HEMA)/diethylene glycol dimethacylate (DEGDMA)-based hydrogel during photopolymerization synthesis. We demonstrated that magnetic rotational spectroscopy provides rich physicochemical information about the gelation process. The method allows one to completely specify the time-dependent viscosity by directly measuring characteristic viscosity and characteristic time. Remarkably, one can analyze not only the polymer solution, but also the suspension enriched with the gel domains being formed. Since the probing nanorods are measured in nanometers, this method can be used for the in vivo mapping of the rheological properties of biofluids and polymers on a microscopic level at short time intervals when other methods fall short. PMID- 22668086 TI - Biological response of nasopharyngeal carcinoma to radiation therapy: a pilot study using serial 18F-FDG PET/CT scans. AB - We used serial (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) to evaluate tumors' maximum standardized uptake value (SUV(max)) before, during, and after radiotherapy to explore the biological behavior of and response to radiation therapy in various subtypes of nasopharyngeal carcinoma (NPC). Sixty-one patients with pathologically diagnosed NPC were prospectively enrolled into the study. WHO type II(B) disease had a higher initial SUV(max) and more significant biological response at the primary site as compared with type II(A) subtype. The two subtypes of WHO type II NPC may significantly differ in their biological behavior and response to radiotherapy. PMID- 22668088 TI - Audio tape sale order form. PMID- 22668087 TI - Sybron. PMID- 22668091 TI - Correction, quality control. PMID- 22668090 TI - Correction. PMID- 22668092 TI - Quality control. PMID- 22668093 TI - Multidisciplinary research-an experiment. PMID- 22668094 TI - Washington. PMID- 22668095 TI - International. PMID- 22668096 TI - States. PMID- 22668098 TI - Technology. PMID- 22668097 TI - Science. PMID- 22668099 TI - Awards. PMID- 22668101 TI - Water research in Norway. PMID- 22668100 TI - Industry. PMID- 22668102 TI - Subsurface organic contaminants. PMID- 22668103 TI - Dionex corporation. PMID- 22668104 TI - Project SEED. PMID- 22668105 TI - New Zealand at a crossroads. PMID- 22668106 TI - Monitoring toxic air pollutants. PMID- 22668108 TI - Vaisala. PMID- 22668107 TI - Chlorinated dioxins as herbicide contaminants. PMID- 22668109 TI - Freshwater acidification from atmospheric deposition of sulfuric acid: A conceptual model. PMID- 22668110 TI - CHEMTECH... because a chemist leads so many lives. PMID- 22668111 TI - Products. PMID- 22668112 TI - Literature. PMID- 22668113 TI - Geochemistry and chemistry of oil shales. PMID- 22668116 TI - The Annual ACS LabGuide- the Definitive Source for. PMID- 22668117 TI - International. PMID- 22668119 TI - professional consulting services directory. PMID- 22668121 TI - Normandeau associates, inc. PMID- 22668122 TI - Immunomodulatory agents in myelofibrosis. AB - INTRODUCTION: The treatment options for patients with myelofibrosis (MF) remain limited. Anemia, thrombocytopenia, extramedullary hematopoiesis, constitutional symptoms, and disease progression are the primary causes of morbidity and mortality. Traditional non-transplant therapies remain non-curative. Moreover, in the JAK2 inhibitor era, no single pharmacologic agent has been shown to improve all MF-related clinical manifestations. Immunomodulatory agents (IMiDs), such as thalidomide and lenalidomide, have been useful in the treatment of some MF patients while newer IMiDs such as pomalidomide are showing promise in MF. AREAS COVERED: This review focuses on the biologic rationales of IMiDs and the clinical results supporting their use in MF. It includes data on the new IMiD, pomalidomide and also explores the possible utility of combining IMiDs with other agents. A PubMed search of articles related to IMiDs and myelofibrosis were conducted. Relevant studies and clinical studies with sample size of > 15 were included. EXPERT OPINION: In the JAK2 inhibitor era, IMiDs are alternative treatments in managing splenomegaly and constitutional symptoms. They remain useful in the treatment of cytopenias. Pomalidomide's good anemia response may lead to its inclusion as one of the frontline anemia therapies in MF. Molecular biomarkers may allow us to identify patients who will respond to IMiDs. PMID- 22668123 TI - Overdose of atypical antipsychotics: clinical presentation, mechanisms of toxicity and management. AB - Historically, treatment for schizophrenia focused on sedation. The advent of the typical antipsychotics resulted in treatment aimed specifically at the underlying disease, but these agents were associated with numerous adverse effects, and were not particularly effective at treatment of the negative symptoms of schizophrenia. As a result, numerous atypical agents have been developed over the past 2 decades, including several agents within the past 5 years. Overdose of antipsychotics remains quite common in Western society. In 2010, poison control centres in the US received nearly 43,000 calls related to atypical antipsychotics alone. Due to underreporting, the true incidence of overdose with atypical antipsychotics is likely much greater. Following overdose of an atypical antipsychotic, the clinical effects observed, such as CNS depression, tachycardia and orthostasis are largely predictable based on the unique receptor binding profile of the agent. This article, which focuses on the atypical antipsychotics commonly used in the treatment of schizophrenia, discusses the features commonly encountered in overdose. Specifically, agents that result in QT prolongation and the corresponding potential for torsades de pointes, as well as unique features encountered with the various medications are discussed. The diagnosis of this overdose is largely based on history. Routine use of drug screens is unlikely to be beneficial. The primary goal of management is aggressive supportive care. Patients with significant CNS depression with associated loss of airway reflexes and respiratory failure need advanced airway management. Hypotension should be treated first with intravenous fluids, with the use of direct acting vasopressors reserved for persistent hypotension. Benzodiazepines should be used for seizures, with barbiturates used for refractory seizures. Intravenous magnesium can be administered for patients with a corrected QT interval exceeding 500 milliseconds. PMID- 22668125 TI - A 10-year follow-up study of patients with severe traumatic brain injury and dysautonomia treated with intrathecal baclofen therapy. AB - PRIMARY OBJECTIVE: To describe the long-term disorders of consciousness in patients with dysautonomia and hypertonia treated with intrathecal baclofen therapy (IBT). METHODS AND PROCEDURES: Forty-three patients with severe traumatic brain injuries who were previously implanted with an intrathecal baclofen pump were included to be evaluated in the long-term with the Coma Recovery Scale Revised. The Barthel Index, the Glasgow Outcome Scale, the Ashworth scale, the scores of hypertonic attacks, of sweating episodes and of voluntary motor responses were used to describe functional abilities and residual impairments. A retrospective analysis highlighted patients' characteristics at admission, before surgery and their complications. MAIN OUTCOMES AND RESULTS: After a mean follow up of 10 years, nine of 43 (20.9%) patients had died, 13/43 (30.2%) patients were severely disabled or in an unresponsive wakefulness syndrome and 21/43 (48.8%) patients had good recovery of consciousness. The latter patients tended to receive IBT later, suggesting a later development of uncontrolled symptoms of dysautonomia and hypertonia. They needed lower doses of baclofen, suggesting that they had less severe symptoms. Their dysautonomia, limb hypertonia and voluntary motor responses improved significantly compared to patients with poor outcome. CONCLUSIONS: Recovery of good long-term consciousness is possible. A low level of consciousness recovery and the early development of severe and persistent symptoms of dysautonomia associated with hypertonia could be linked to poor long term outcome. PMID- 22668126 TI - Oscillations of chiral preference in proline clusters. AB - Ion mobility/mass spectrometry techniques are used to study the chiral preferences of small proline clusters (containing 2 to 23 proline monomers) produced by electrospray ionization. By varying the composition of the electrospray solution from enantiomerically pure (100% L or 100% D) to racemic (50:50 L:D), it is possible to delineate which cluster sizes prefer homochiral (resolved) or heterochiral (antiresolved) compositions. The results show a remarkable oscillation in chiral preference. Singly protonated clusters, [xPro+H](+) (where x corresponds to the number of prolines), favor homochiral assemblies (for x = 4, 6, 11 and 12); heterochiral structures are preferred (although the preferences are not as strong) for x = 5 and 7. Larger, doubly protonated clusters [xPro+2H](2+) favor homochiral assemblies for x = 18, 19, and 23 and heterochiral structures for x = 14, 16, 17, 20, 21, and 22. Some of the variations that are observed can be rationalized through simple structures that would lead to especially stable geometries. It is suggested that some antiresolved clusters, such as [22Pro+2H](2+), may be comprised of resolved D- and L-proline domains. PMID- 22668127 TI - Water-soluble Mo3S4 clusters bearing hydroxypropyl diphosphine ligands: synthesis, crystal structure, aqueous speciation, and kinetics of substitution reactions. AB - The [Mo(3)S(4)Cl(3)(dhprpe)(3)](+) (1(+)) cluster cation has been prepared by reaction between Mo(3)S(4)Cl(4)(PPh(3))(3) (solvent)(2) and the water-soluble 1,2 bis(bis(hydroxypropyl)phosphino)ethane (dhprpe, L) ligand. The crystal structure of [1](2)[Mo(6)Cl(14)] has been determined by X-ray diffraction methods and shows the typical incomplete cuboidal structure with a capping and three bridging sulfides. The octahedral coordination around each metal center is completed with a chlorine and two phosphorus atoms of the diphosphine ligand. Depending on the pH, the hydroxo group of the functionalized diphosphine can substitute the chloride ligands and coordinate to the cluster core to give new clusters with tridentate deprotonated dhprpe ligands of formula [Mo(3)S(4)(dhprpe-H)(3)](+) (2(+)). A detailed study based on stopped-flow, (31)P{(1)H} NMR, and electrospray ionization mass spectrometry techniques has been carried out to understand the behavior of acid-base equilibria and the kinetics of interconversion between the 1(+) and the 2(+) forms. Both conversion of 1(+) to 2(+) and its reverse process occur in a single kinetic step, so that reactions proceed at the three metal centers with statistically controlled kinetics. The values of the rate constants under different conditions are used to discuss on the mechanisms of opening and closing of the chelate rings with coordination or dissociation of chloride. PMID- 22668124 TI - A review of neuroprotection pharmacology and therapies in patients with acute traumatic brain injury. AB - Traumatic brain injury (TBI) affects 1.6 million Americans annually. The injury severity impacts the overall outcome and likelihood for survival. Current treatment of acute TBI includes surgical intervention and supportive care therapies. Treatment of elevated intracranial pressure and optimizing cerebral perfusion are cornerstones of current therapy. These approaches do not directly address the secondary neurological sequelae that lead to continued brain injury after TBI. Depending on injury severity, a complex cascade of processes are activated and generate continued endogenous changes affecting cellular systems and overall outcome from the initial insult to the brain. Homeostatic cellular processes governing calcium influx, mitochondrial function, membrane stability, redox balance, blood flow and cytoskeletal structure often become dysfunctional after TBI. Interruption of this cascade has been the target of numerous pharmacotherapeutic agents investigated over the last two decades. Many agents such as selfotel, pegorgotein (PEG-SOD), magnesium, deltibant and dexanabinol were ineffective in clinical trials. While progesterone and ciclosporin have shown promise in phase II studies, success in larger phase III, randomized, multicentre, clinical trials is pending. Consequently, no neuroprotective treatment options currently exist that improve neurological outcome after TBI. Investigations to date have extended understanding of the injury mechanisms and sites for intervention. Examination of novel strategies addressing both pathological and pharmacological factors affecting outcome, employing novel trial design methods and utilizing biomarkers validated to be reflective of the prognosis for TBI will facilitate progress in overcoming the obstacles identified from previous clinical trials. PMID- 22668128 TI - Spin reorientation in the square-lattice antiferromagnets RMnAsO (R = Ce, Nd): density functional analysis of the spin-exchange interactions between the rare earth and transition-metal ions. AB - The spin reorientation (SR) phenomenon of the square-lattice antiferromagnets RMnAsO (R = Ce, Nd) was investigated by analyzing the spin-exchange interactions between the rare-earth and the transition-metal ions (R(3+) and Mn(2+), respectively) on the basis of density functional calculations. It is found that the symmetry and strength of the Dzyaloshinskii-Moriya (DM) interaction are determined primarily by the partially filled 4f states of the R(3+) ions and that the DM and biquadratic (BQ) exchanges between the R(3+) and the Mn(2+) ions are unusually strong and control the observed spin reorientation phenomenon. Below their SR temperature, the Mn(2+) and Ce(3+) moments are orthogonal in CeMnAsO but are collinear in NdMnAsO, because the DM interaction dominates over the BQ interaction for CeMnAsO, while the opposite is the case for NdMnAsO. Experiments designed to test the implications of our findings are proposed. PMID- 22668129 TI - Reversibility and diffusion in mandelythiamin decarboxylation. Searching dynamical effects in decarboxylation reactions. AB - Decarboxylation of mandelylthiamin in aqueous solution is analyzed by means of quantum mechanics/molecular mechanics simulations including solvent effects. The free energy profile for the decarboxylation reaction was traced, assuming equilibrium solvation, while reaction trajectories allowed us to incorporate nonequilibrium effects due to the solvent degrees of freedom as well as to evaluate the rate of the diffusion process in competition with the backward reaction. Our calculations that reproduce the experimental rate constant show that decarboxylation takes place with a non-negligible free energy barrier for the backward reaction and that diffusion of carbon dioxide is very fast compared to the chemical step. According to these findings catalysts would not act by preventing the backward reaction. PMID- 22668130 TI - Invariance of vestibulo-ocular reflex gain to head impulses in pitch at different initial eye-in-orbit elevations: implications for Alexander's law. AB - CONCLUSIONS: These findings are in line with previous data on the horizontal vestibulo-ocular reflex (VOR) from this laboratory and suggest that eye position signals do not modulate natural vestibular responses. Hence, the Alexander's law (AL) phenomenon cannot be interpreted simply as a consequence of vestibular or oculomotor nuclei activity modulation with desired gaze. BACKGROUND: AL states that the intensity of the spontaneous nystagmus of a patient with a unilateral vestibular lesion grows with increasing gaze in the direction of the fast phase. Some of the mechanisms proposed to account for the gaze effects assume a direct modification of the normal VOR by eye position signals. We tested the validity of these assumptions and investigated the effects of gaze direction on the normal vertical human VOR in the behaviorally relevant high frequency range. METHODS: Head and eye movements were recorded with the search coil method during passive head impulses in pitch, while subjects were asked to hold gaze at various elevation angles in 8 degrees steps within +/- 16 degrees from the straight ahead reference position. RESULTS: Upward and downward head rotations produced VOR gains of similar magnitude. Furthermore, the gain remained unaffected by eye in-orbit position for both upward and downward head impulses. PMID- 22668131 TI - Myogenin expression in facial muscle following damage to the facial nerve. AB - CONCLUSION: Gene analysis of facial muscle may be a promising way to detect denervation of facial muscle, helping to determine the prognosis of a facial palsy early in its progression. OBJECTIVES: In the treatment of intratemporal facial palsy, early diagnosis of neural damage is important in deciding about therapeutic modalities. In this study, we investigated the relationship between the severity of facial palsy and the level of myogenin expressed in the facial muscle. METHODS: The animals were divided into two groups, depending on whether the facial nerve was resected or compressed. Expression of myogenin mRNA was examined using real-time PCR and in situ hybridization of the facial muscle following the nerve damage. RESULTS: Increased expression of myogenin was observed in the nerve resection group, while no such increase was seen in the nerve compression group. In situ hybridization indicated that myogenin was expressed exclusively in satellite cells around the denervated muscle fibers. PMID- 22668132 TI - Sex differences in mercury contamination of birds: testing multiple hypotheses with meta-analysis. AB - The sex of a bird can, in principle, affect exposure and accumulation of mercury. One conventional explanation for sex differences in mercury burden suggests female birds should have lower concentrations than conspecific males, because breeding females can depurate methylmercury to their eggs. However, sex differences in body burden of mercury among birds are not consistent. We used meta-analysis to synthesize 123 male-female comparisons of mercury burden from 50 studies. For breeding birds, males had higher concentrations of mercury than did females, supporting egg depuration as a mechanism. However, the percentage of female body mass represented by a clutch did not significantly predict the magnitude of the sex difference in mercury contamination, as predicted. Furthermore, whether species were semialtrical or altrical versus semiprecocial or precocial also did not explain sex differences in mercury burden. Foraging guild of a species did explain near significant variation in sex differences in mercury burden where piscivores and invertivores showed significant sex differences, but sex differences were not detected for carnivores, herbivores, insectivores, and omnivores. The magnitude and direction of sexual size dimorphism did not explain variation in sex differences in mercury burden among breeding birds. We reveal targeted research directions on mechanisms for sex differences in mercury and confirm that sex is important to consider for environmental risk assessments based on breeding birds. PMID- 22668196 TI - Type I hair cell regeneration induced by Math1 gene transfer following neomycin ototoxicity in rat vestibular sensory epithelium. AB - CONCLUSION: In the current study, hair cells of vestibular terminal organs in rats were completely eliminated with trans-scala vestibuli injection of neomycin, and then the Math1 gene was transferred. It was shown that type I vestibular hair cells were regenerated and synapses were formed. OBJECTIVES: The objective of this study was to identify the cell type of the regenerated vestibular hair cells and relative innervation and synaptic linkage after hair cells of vestibular terminal organs in rats were completely eliminated. METHODS: Neomycin injection was used to eliminate all the vestibular terminal organs, and then the animals were treated with an injection of Ad-Math1-EGFP in the scala vestibuli of the cochlea. RESULTS: Math1 gene transfer into the inner ear induced type I hair cell regeneration and synaptic formation. However, neither the number nor the appearance of the hair cells was normal. PMID- 22668199 TI - A faster running speed is associated with a greater body weight loss in 100-km ultra-marathoners. AB - In 219 recreational male runners, we investigated changes in body mass, total body water, haematocrit, plasma sodium concentration ([Na(+)]), and urine specific gravity as well as fluid intake during a 100-km ultra-marathon. The athletes lost 1.9 kg (s = 1.4) of body mass, equal to 2.5% (s = 1.8) of body mass (P < 0.001), 0.7 kg (s = 1.0) of predicted skeletal muscle mass (P < 0.001), 0.2 kg (s = 1.3) of predicted fat mass (P < 0.05), and 0.9 L (s = 1.6) of predicted total body water (P < 0.001). Haematocrit decreased (P < 0.001), urine specific gravity (P < 0.001), plasma volume (P < 0.05), and plasma [Na(+)] (P < 0.05) all increased. Change in body mass was related to running speed (r = -0.16, P < 0.05), change in plasma volume was associated with change in plasma [Na(+)] (r = 0.28, P < 0.0001), and change in body mass was related to both change in plasma [Na(+)] (r = -0.36) and change in plasma volume (r = 0.31) (P < 0.0001). The athletes consumed 0.65 L (s = 0.27) fluid per hour. Fluid intake was related to both running speed (r = 0.42, P < 0.0001) and change in body mass (r = 0.23, P = 0.0006), but not post-race plasma [Na(+)] or change in plasma [Na(+)] (P > 0.05). In conclusion, faster runners lost more body mass, runners lost more body mass when they drank less fluid, and faster runners drank more fluid than slower runners. PMID- 22668197 TI - Blood-nanoparticle interactions and in vivo biodistribution: impact of surface PEG and ligand properties. AB - Theranostic nanoparticles (NPs) cannot reach their target tissue without first passing through blood; however, the influence of blood protein and blood cell interactions on NP biodistribution are not well understood. The current work shows that 30 nm PEGylated gold NPs (GNPs) interact not only with blood proteins as thought before but also with blood cells (especially platelets and monocytes) in vivo and that longer blood circulation correlates strongly with tumor uptake. Further, GNP surface properties such as negative charge or lyophilization had either a minimal (i.e., charge) or 15-fold increase (i.e., fresh vs lyophilized) in blood retention times and tumor uptake. Tumor accumulation was increased over 10-fold by use of a bioactive ligand (i.e., TNF) on the lyophilized GNP surface. Resident macrophages were primarily responsible for the bulk of GNP uptake in liver while spleen uptake was highly surface property dependent and appears to involve macrophages and cellular interaction between the red and white pulp. This study shows that the PEG layer and ligand on the surface of the NP are critical to blood interactions and eventual tumor and RES organ biodistribution in vivo. PMID- 22668200 TI - Primary amine, thiourea-based dual catalysis motif for synthesis of stereogenic, all-carbon quaternary center-containing cycloalkanones. AB - The enantioselective synthesis of alpha,alpha-disubstituted cycloalkanones has been developed using a primary amine, thiourea-based dual catalysis pathway. A range of electrophiles and ring sizes are tolerated under the reaction conditions. A possible catalytic cycle is presented to explain the reactivity. PMID- 22668201 TI - Intravitreal bevacizumab treatment for macular edema due to branch retinal vein occlusion in a clinical setting. AB - PURPOSE: To report the functional and anatomical outcome of intravitreal bevacizumab (IVB) treatment for macular edema due to branch retinal vein occlusion (BRVO) in a clinical setting. METHODS: The files of 45 patients treated with IVB for BRVO-induced macular edema at a tertiary medical center in 2007-2010 were reviewed. All received three loading doses (1.25 mg) and were followed every 6 weeks. Treatment was repeated for persistent or recurrent edema. If the edema did not resolve after 4-6 injections, grid laser photocoagulation was performed. RESULTS: Mean patient age was 70.7 years (SD 8.5); mean follow-up time, 18.8 months (SD 8.3); mean number of injections, 8.8 (SD 3.8). Fourteen patients (33%) received grid laser treatment before bevacizumab and 23 (51%) after. Mean logMAR visual acuity (VA) was 0.63 (SD 0.43) before treatment (Snellen, 20/140) and 0.4 (SD 0.43) (Snellen, 20/70) after (p < 0.0005). Corresponding central macular thickness (CMT) values were 382.2 microns (SD 155.6) and 320.5 microns (SD 172.8) (p= 0.028). Positive correlations were found between initial VA and initial and final CMT (p = 0.004) and between gain in VA and reduction in CMT (p = 0.03). There was no statistically significant difference in mean initial or final VA and CMT between patients who received grid laser treatment before or during the study and those who did not. CONCLUSIONS: IVB treatment improves visual function and reduces CMT in patients with BRVO-induced macular edema. PMID- 22668202 TI - Rates of killing of methicillin-resistant Staphylococcus aureus by ceftaroline, daptomycin, and telavancin compared to that of vancomycin. AB - Treatment failure of methicillin-resistant Staphylococcus aureus (MRSA) remains an important concern. In order to investigate new MRSA treatment modalities, we used standard time-kill assays to determine the in vitro killing rate of 22 strains of MRSA by vancomycin, telavancin, daptomycin, and ceftaroline. Studies were carried out with 7-10-times the minimum bactericidal concentrations of each antibiotic in broth culture for 24 h, with subculture at 4, 8, and 24 h. We found that killing by ceftaroline closely paralleled that of vancomycin. Telavancin killed bacteria significantly more slowly, whereas daptomycin killed significantly more rapidly. PMID- 22668203 TI - Structural convergence of maize and wheat straw during two-year decomposition under different climate conditions. AB - Straw decomposition plays an important role in soil carbon sequestration. Litter quality and climate condition are considered to be key factors that regulate straw decomposition. This study investigated the decomposition characteristics of wheat and maize straw under cold temperate, warm temperate, and midsubtropic climate conditions, and examined whether the chemical structures of straw residues became similar during decomposition under different climate conditions. Straws were put in 0.074-mm-mesh size litter bags to exclude soil fauna and buried in black soil plots at three experimental stations located in the aforementioned climate regions to rule out the impact of soil type. The decomposition rate constants of wheat straw and maize straw increased linearly with temperature, and the former was more sensitive to temperature. Climate conditions and straw quality had marked effects on the residual material structure in the first half year of decomposition, but then decreased. Wheat and maize straw showed common decomposition characteristics with a decrease of O/N alkyl carbons and di-O-alkyls, and a simultaneous increase of alkyl carbons, aromatic carbons, aromatic C-O groups, and COO/N-C ? O groups. Overall, the results indicated that the chemical compositions of the two types of straw became similar after 2-year decomposition under different climate conditions. PMID- 22668204 TI - Dendritic cells and the assessment in vitro of skin sensitizing potential. AB - It is now well established that dendritic cells (DC) play pivotal roles in the initiation and orchestration of adaptive immune responses, including cutaneous immune responses to chemical allergens that drive the acquisition of skin sensitization. It is not unexpected, therefore, that a large number, and wide variety, of proposed approaches for the identification of skin sensitizing chemicals in vitro are based upon the use of cultured DC or DC-like cells. The use of DC in this context is legitimate. However, with our rapidly increasing understanding of the diversity of cutaneous DC with respect to both phenotype and function, it is timely now to review briefly the potential limitations and interpretive difficulties that are associated with the use of DC-based assays. Among the important considerations are the fact that chemical-induced changes in the characteristics and function of cultured DC will not necessarily reflect accurately the events that that support the development of skin sensitization in vivo. In addition, most DC-based assays are predicated on a view that cutaneous DC have as their primary function the initiation of adaptive immune responses. However, it is now appreciated that cutaneous DC, and in particular epidermal Langerhans cells (LC), may also play important immunoregulatory roles that serve to limit and contain skin immune responses. Notwithstanding these considerations there is reason to believe that at least some in vitro DC-based assays are of value, and indeed some are currently the subject of a formal validation process. However, it is appropriate that such assays are configured and interpreted carefully, and with an appreciation of the complexity of DC biology. PMID- 22668205 TI - Acephaly: further evidence for disruption but not for amniotic bands. AB - Complete absence of the fetal head in singleton pregnancies is a very rare defect; to our knowledge there are only 7 reported cases. Decapitation by amniotic bands has been considered as the most probable cause. However, in none of the described cases except one were amniotic bands, constriction rings, or other related findings observed, raising the possibility that mechanisms other than amputation by amniotic bands are involved. We present a further case of acephaly and discuss the role of amniotic bands and alternative mechanisms of decapitation and a possible sequence of events leading to acephaly. PMID- 22668207 TI - Sybron. PMID- 22668206 TI - Multiscale modeling reveals poisoning mechanisms of MgO-supported Au clusters in CO oxidation. AB - Catalyst deactivation mechanisms on MgO-supported Au(6) clusters are studied for the CO oxidation reaction via first-principle kinetic Monte Carlo simulations and shown to depend on support vacancies. In defect-poor MgO or in the presence of a Mg vacancy, O(2) does not bind to the clusters and the catalyst is poisoned by CO. On Au clusters interacting with O vacancies of the support, O(2) can be chemisorbed and transient activity is observed. In this case, an unexpected catalyst "breathing" mechanism (restructuring) leads to carbonate formation and catalyst deactivation, rationalizing several experimental observations. Our study underscores the importance of the cluster's charge state and dynamics on catalytic activity. PMID- 22668208 TI - Chemists-How's this for user friendly? PMID- 22668210 TI - International. PMID- 22668209 TI - "The review is late because . . .". PMID- 22668212 TI - States. PMID- 22668213 TI - Awards. PMID- 22668211 TI - Washington. PMID- 22668214 TI - Science. PMID- 22668215 TI - Technology. PMID- 22668217 TI - EPA's rules on radiation. PMID- 22668216 TI - Industry. PMID- 22668218 TI - Photochemistry of natural water systems. PMID- 22668220 TI - Regulating air toxics. PMID- 22668219 TI - Roger adams: scientist and statesman. PMID- 22668221 TI - A reassessment of crop loss from ozone. PMID- 22668222 TI - Microbial resistance to heavy metals. PMID- 22668225 TI - Literature. PMID- 22668224 TI - Products. PMID- 22668226 TI - Wiley-interscience. PMID- 22668228 TI - Courses. PMID- 22668231 TI - Want to get ahead? You. PMID- 22668229 TI - International. PMID- 22668232 TI - professional consulting services directory. PMID- 22668233 TI - Classified section. PMID- 22668235 TI - New treatment of subglottic stenosis due to Wegener's granulomatosis. AB - CONCLUSIONS: The presented new endoscopic surgical technique offers a safe and successful approach for treatment of subglottic stenosis due to Wegener's granulomatosis. OBJECTIVE: Subglottic stenosis is a potentially limiting and complex condition among patients with Wegener's granulomatosis. It causes various symptoms and often requires interventional therapy. The purpose of this study was to evaluate a new endoscopic submucosal technique. METHODS: Altogether 13 consecutive patients with subglottic stenosis due to Wegener's granulomatosis were treated with a new endoscopic technique. The procedure was carried out endoscopically, removing the stenotic part submucosally, sealing back the raised mucosal flap, and the bare areas were soaked with mitomycin-C. Follow-up telephone interviews were carried out and hospital records were reviewed. RESULTS: Patients included 3 males and 10 females, with an average age of 37.5 years. A total of 37 procedures were performed, with an average of 2.8 procedures per patient. There was a statistically significant reduction in the all symptoms related to the stenoses (p < 0.05). Mean follow-up period was 3.5 years (range 1.5-6.5 years). Overall success rate was 85%. Only one patient relapsed following adequate medical and surgical treatment. No perioperative mortality was recorded. PMID- 22668236 TI - Preface: detection, modeling, and compensation of organ motion and deformation part I. PMID- 22668237 TI - Motion compensation strategies in magnetic resonance imaging. AB - Image quality in magnetic resonance imaging (MRI) is considerably affected by motion. Therefore, motion is one of the most common sources of artifacts in contemporary cardiovascular MRI. Such artifacts in turn may easily lead to misinterpretations in the images and a subsequent loss in diagnostic quality. Hence, there is considerable research interest in strategies that help to overcome these limitations at minimal cost in time, spatial resolution, temporal resolution, and signal-to-noise ratio. This review summarizes and discusses the three principal sources of motion: the beating heart, the breathing lungs, and bulk patient movement. This is followed by a comprehensive overview of commonly used compensation strategies for these different types of motion. Finally, a summary and an outlook are provided. PMID- 22668238 TI - Magnetic resonance- and ultrasound imaging-based elasticity imaging methods: a review. AB - Elasticity imaging methods aim at measuring the mechanical behavior of soft tissues by using medical imaging modalities, such as ultrasonography or magnetic resonance imaging. The initial motivation behind these techniques, and still the main one, is the need for new diagnostic tools based on the visualization of tissue stiffness. Recent developments have demonstrated the potential that elasticity imaging methods can offer in new fields other than direct medical diagnosis, such as the field of in vivo biomechanical characterization. After a short description of the general principles behind elasticity imaging, this review illustrates some of the most original clinical applications. The use of elastography for quantitative mechanical characterization is particularly emphasized, and original applications of these methods to several biomedical research fields are reviewed. PMID- 22668239 TI - Review on 4D models for organ motion compensation. AB - Minimal invasive tumor therapies are getting ever more sophisticated with novel treatment approaches and new devices allowing for improved targeting precision. Applying these effectively requires precise localization of the structures of interest. Vital processes, such as respiration and heartbeat, induce organ motion, which cannot be neglected during therapy. This review focuses on 4D organ models to compensate for respiratory motion during therapy. An overview is given on the effects of motion on the therapeutical outcome, methods required to capture and quantify respiratory motion, range of reported tumor motion, types of surrogates used when tumors are not directly observable, and methods for temporal prediction of surrogate motion. Organ motion models, which predict the location of structures of interest from surrogates measured during therapy, are discussed in detail. PMID- 22668240 TI - Efficient finite element methods for deformable bodies in medical applications. AB - Simulation techniques for deformable bodies are of major relevance for a broad range of medical applications. In recent decades, a lot of work has been performed to improve simulation methods, allowing interactivity or even real time. However, this work often focused on applications such as computer games or virtual environments, where physical accuracy is not a primary goal. The goal of this report is to give an overview of efficient physics-based techniques for deformable objects, focusing on finite element methods, and to discuss the applicability of these techniques in medical scenarios. As a result, we focus on techniques that are amenable to simulating highly resolved meshes, which for instance can be generated from computed tomography (CT) or magnetic resonance (MR) images, and we review the so-called corotated finite element method that has shown a high potential in recent years. Specifically, we will capture in detail the related work in this field and demonstrate the current state of the art in efficient deformable bodies simulations. PMID- 22668241 TI - Valproic acid for the treatment of malignant gliomas: review of the preclinical rationale and published clinical results. AB - INTRODUCTION: Glioblastoma multiforme is the most common and aggressive primary brain tumor. Valproate has been used as an anti-epileptic drug and mood stabilizer for decades. Recently, it was found to inhibit the proliferation of various cancers including glioblastoma multiforme. AREAS COVERED: We provide a comprehensive review of the mechanisms of action of valproate in gliomas, of its potential side effects and of the published clinical results obtained with this drug in glioblastomas. Valproate inhibits a subset of histone deacetylases and cellular kinases, and affects gene transcription through histone hyperacetylation, DNA hypomethylation and the modulation of several transcription factors. As a result, VPA induces differentiation of glioma cells, can prevent their invasion in surrounding tissues and may inhibit tumor angiogenesis. VPA can also inhibit DNA repair, thereby potentiating cytotoxic treatments such as chemotherapies or radiation therapy. Based on these mechanisms and case reports of glioblastoma remissions following VPA treatment, several clinical studies currently assess the therapeutic potential of VPA in glioma therapy. EXPERT OPINION: The combination of VPA treatment with chemotherapy and radiotherapy in glioblastoma appears a rational option that deserves well-designed prospective clinical trials that assess the efficacy and the molecular characteristics of the responding tumors in these patients. PMID- 22668242 TI - beta-Nitro-5,10,15-tritolylcorroles. AB - Functionalization of the beta-pyrrolic positions of the corrole macrocycle with NO(2) groups is limited at present to metallocorrolates due to the instability exhibited by corrole free bases under oxidizing conditions. A careful choice of the oxidant can limit the transformation of corroles into decomposition products or isocorrole species, preserving the corrole aromaticity, and thus allowing the insertion of nitro groups onto the corrole framework. Here we report results obtained by reacting 5,10,15-tritolylcorrole (TTCorrH(3)) with the AgNO(2)/NaNO(2) system, to give mono- and dinitrocorrole derivatives when stoichiometry is carefully controlled. Reactions were found to be regioselective, affording the 3-NO(2)TTCorrH(3) and 3,17-(NO(2))(2)TTCorrH(3) isomers as the main products in the case of mono- and disubstitution, in 53 and 20% yields, respectively. In both cases, traces of other mono- and disubstituted isomers were detected, which were structurally characterized by X-ray crystallography. The influence of the beta-nitro substituents on the corrole properties is studied in detail by UV-visible, electrochemical, and spectroelectrochemical characterization of these functionalized corroles. Density functional theory (DFT) and time-dependent DFT (TDDFT) calculations of the ground and excited state properties of these beta-nitrocorrole derivatives also afforded significant information, closely matching the experimental observations. It is found that the beta-NO(2) substituents conjugate with the pi-aromatic system of the macrocycle, which initiates significant changes in both the spectroscopic and redox properties of the so functionalized corroles. This effect is more pronounced when the nitro group is introduced at the 2-position, because in this case the conjugation is, for steric reasons, more efficient than in the 3-nitro isomer. PMID- 22668243 TI - Ligand effects on rates and regioselectivities of Rh(I)-catalyzed (5 + 2) cycloadditions: a computational study of cyclooctadiene and dinaphthocyclooctatetraene as ligands. AB - The first theoretical study on the effects of ligands on the mechanism, reactivities, and regioselectivities of Rh(I)-catalyzed (5 + 2) cycloadditions of vinylcyclopropanes (VCPs) and alkynes has been performed using density functional theory (DFT) calculations. Highly efficient and selective intermolecular (5 + 2) cycloadditions of VCPs and alkynes have been achieved recently using two novel rhodium catalysts, [Rh(dnCOT)](+)SbF(6)(-) and [Rh(COD)](+)SbF(6)(-), which provide superior reactivities and regioselectivities relative to that of the previously reported [Rh(CO)(2)Cl](2) catalyst. Computationally, the high reactivities of the dnCOT and COD ligands are attributed to the steric repulsions that destabilize the Rh-product complex, the catalyst resting state in the catalytic cycle. The regioselectivities of reactions with various alkynes and different Rh catalysts are investigated, and a predictive model is provided that describes substrate-substrate and ligand-substrate steric repulsions, electronic effects, and noncovalent pi/pi and C-H/pi interactions. In the reactions with dnCOT or COD ligands, the first new C-C bond is formed proximal to the bulky substituent on the alkyne to avoid ligand-substrate steric repulsions. This regioselectivity is reversed either by employing the smaller [Rh(CO)(2)Cl](2) catalyst to diminish the ligand-substrate repulsions or by using aryl alkynes, for which the ligand-substrate interactions become stabilizing due to pi/pi and C H/pi dispersion interactions. Electron-withdrawing groups on the alkyne prefer to be proximal to the first new C-C bond to maximize metal-substrate back-bonding interactions. These steric, electronic, and dispersion effects can all be utilized in designing new ligands to provide regiochemical control over product formation with high selectivities. The computational studies reveal the potential of employing the dnCOT family of ligands to achieve unique regiochemical control due to the steric influences and dispersion interactions associated with the rigid aryl substituents on the ligand. PMID- 22668244 TI - Redetermination of the Crystal and Molecular Structure of trans-Diaquobis(2,4 pentanedione)nickel(II) Perchlorate, Including Location and Refinement of Hydrogen Atoms. PMID- 22668245 TI - Antioxidants as antidepressants: fact or fiction? AB - Depression is a medical condition with a complex biological pattern of aetiology, involving genetic and epigenetic factors, along with different environmental stressors. Recent evidence suggests that oxidative stress processes might play a relevant role in the pathogenic mechanism(s) underlying many major psychiatric disorders, including depression. Reactive oxygen and nitrogen species have been shown to modulate levels and activity of noradrenaline (norepinephrine), serotonin, dopamine and glutamate, the principal neurotransmitters involved in the neurobiology of depression. Major depression has been associated with lowered concentrations of several endogenous antioxidant compounds, such as vitamin E, zinc and coenzyme Q10, or enzymes, such as glutathione peroxidase, and with an impairment of the total antioxidant status. These observations introduce new potential targets for the development of therapeutic interventions based on antioxidant compounds. The present review focuses on the possible role of oxidative stress processes in the pathogenesis of depression. The therapeutic potential of antioxidant compounds as a co-adjuvant treatment to conventional antidepressants is discussed. For instance, N-acetyl-cysteine has been shown to have a significant benefit on depressive symptoms in a randomized placebo controlled trial. Additionally, curcumin, the yellow pigment of curry, has been shown to strongly interfere with neuronal redox homeostasis in the CNS and to possess antidepressant activity in various animal models of depression, also thanks to its ability to inhibit monoamine oxidases. There is an urgent need to develop better tolerated and more effective treatments for depressive disorders and several antioxidant treatments appear promising and deserve further study. PMID- 22668246 TI - Comparative effectiveness of atypical antipsychotics in schizophrenia: what have real-world trials taught us? AB - Real-world, effectiveness studies add an important new dimension to the evaluation of the benefits of individual antipsychotics. Efficacy studies have already shown the unique effectiveness of clozapine, and suggested improved outcomes for olanzapine compared with some atypical antipsychotics and a reduced tendency to produce acute and chronic movement disorders for atypical compared with typical drugs. Recent effectiveness studies largely confirm these prior observations. The CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness), CUtLASS (Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study) and SOHO (Schizophrenia Outpatient Health Outcomes) programmes confirmed the superiority of clozapine over other antipsychotics; CATIE and SOHO also confirmed olanzapine as probably the second most effective antipsychotic. Effectiveness studies have confirmed the high incidence of adverse metabolic effects with clozapine, olanzapine and (with less certainty) quetiapine but the ZODIAC (Ziprasidone Observational Study of Cardiac Outcomes) study found no excess cardiovascular events or deaths for olanzapine compared with ziprasidone. Prior observations on reduced frequency of movement disorders for second-generation versus first-generation antipsychotics were also largely (but not uniformly) supported. Overall, recent real-world studies have done much to confirm prior observations from efficacy-based randomized, controlled trials. PMID- 22668247 TI - A comprehensive review of rapid-onset opioids for breakthrough pain. AB - Breakthrough pain (BTP) is a transitory pain (reaching maximum severity in ~15 minutes and lasting ~60 minutes in patients with cancer) that occurs despite the management of chronic pain with long-term around-the-clock analgesia. BTP occurs in 33-65% of patients with chronic cancer pain and in ~70% of patients with chronic noncancer pain. BTP has historically been managed with short-acting opioids; however, these medications have a pharmacokinetic profile that does not correlate with the sudden onset and short time to maximum severity of BTP. Interest in rapid-onset opioids to relieve BTP has therefore been growing. This comprehensive review aims to summarize the currently available clinical data for the approved rapid-onset opioids, which comprise different formulations of fentanyl, a MU-opioid receptor agonist with anaesthetic and analgesic properties. Administration routes for fentanyl in the management of BTP currently include the transmucosal and intranasal routes; an intrapulmonary formulation is also in development. The findings of this review suggest that the efficacy and safety of the approved rapid-onset opioids are comparable. PMID- 22668248 TI - Indirect electrochemical Cr(III) oxidation in KOH solutions at an Au electrode: the role of oxygen reduction reaction. AB - The indirect electro-oxidation of Cr(III) by in situ generated superoxide at a gold electrode has been investigated in KOH solutions using cyclic voltammetry and UV-vis spectroscopy. It is observed that the indirect Cr(III) oxidation behavior is substantially affected by the media pH and there is a pH-modulated oxygen reduction reaction (ORR) process to generate reactive oxygen species which promotes Cr(III) oxidation. The ORR in KOH solutions is attributed to a quasi reversible diffusion-controlled reaction. In dilute KOH solution (0.2 M), 4e reduction occurs and no reactive oxygen species are generated for the indirect Cr(III) oxidation. Moreover, Cr(III) oxidation is inhibited due to competition for the electrode active sites. As the alkaline concentration increases (3.0 M), the protonation of superoxide is greatly suppressed, and thus, 1e ORR to generate superoxide is observed. This change in mechanism facilitates the indirect Cr(III) oxidation through the superoxide as a mediator to oxidize Cr(III) to Cr(IV), which is the rate-determining step of Cr(III) oxidation to Cr(VI). PMID- 22668249 TI - Fluxionality in the chemical reactions of transition metal oxide clusters: the role of metal, spin state, and the reactant molecule. AB - The phenomenon of fluxionality in the reactions of transition metal oxide clusters provides many opportunities in various catalytic and industrial processes. To gain a better understanding into the various factors influencing this phenomenon, we have carried out an electronic structure investigation of the fluxionality pathways when W(3)O(6)(-) and Mo(3)O(6)(-) clusters react with hydrogen sulfide and ammonia. The study illustrates how the metal (W vs Mo), different spin states of the anionic metal oxide cluster (doublet vs quartet), and the nature of the nonmetal in the small molecule (O vs S vs N), all affect the fluxionality pathway. The thermodynamically facile fluxionality pathway with H(2)S detaches both the hydrogens from hydrogen sulfide and can thus be very useful in the petrochemical and desulfurization industries. The fluxionality pathway with NH(3) results in interesting metal-bound imines and bridged amines. However, the overall fluxionality process with NH(3) is found to be thermodynamically unfavorable. PMID- 22668312 TI - A new audio processor for combined electric and acoustic stimulation for the treatment of partial deafness. AB - CONCLUSION: The results of this study demonstrate that a conversion from the Duet to Duet 2 audio processor greatly improved patient satisfaction and subjective benefits. OBJECTIVES: The aims of this study were to compare the DUET 2 audio processor to the DUET speech processor and to evaluate DUET 2 user satisfaction subjectively. METHODS: Ten experienced electric acoustic stimulation (EAS) users following partial deafness treatment upgraded from the MED-EL DUET to the DUET 2 were tested with the adaptive auditory speech test, Pruszewicz monosyllabic word test, visual analog scales, and Duet 2 user questionnaire. Tests were performed post-upgrade and compared simultaneously to the DUET at three test intervals over 3 months. RESULTS: Objective analyses showed that all subjects performed as well with the DUET 2 as the DUET. There was a tendency toward better results with the DUET 2. Subjective testing indicated DUET 2 user preference upon speech and musical stimuli. DUET 2 subject satisfaction was high for wearing comfort, sound quality, and for FineTuner and Private Alert features. PMID- 22668313 TI - Intravitreous bevacizumab treatment for macular edema due to central retinal vein occlusion. AB - PURPOSE: To investigate the visual and anatomical effects of intravitreal bevacizumab treatment of macular edema due to central retinal vein occlusion (CRVO). METHODS: Data were collected by medical chart review for 35 consecutive patients (35 eyes) with CRVO-induced macular edema treated with intravitreal bevacizumab in 2007-2010 and followed for at least 6 months. All patients received 3-4 loading doses (1.25 mg) with follow-up every 6-8 weeks and repeated injections as necessary. RESULTS: Mean patient age was 65.5 years (SD 13.5); mean follow-up time, 17.7 months (SD 10.8); mean number of injections, 9.3 (SD 5). Mean logMAR visual acuity (VA) improved from 0.9 (SD 0.49) at baseline to 0.7 (SD 0.5) at the last visit; corresponding Snellen values were 6/98 and 6/15 (p = 0.009). Four patients (11%) lost >=3 lines, and 13 patients (37%) gained >=3 lines. There was a positive correlation between initial and final VA (p < 0.0005). Central macular thickness (CMT) measured 489.5 microns (SD 175) at baseline and 395 microns (SD 223) at the last visit (p = 0.24). VA gain was positively correlated with CMT reduction (p < 0.0001). CONCLUSIONS: Intravitreal bevacizumab treatment of CRVO-induced macular edema improves vision, especially in patients with good initial VA. PMID- 22668314 TI - Effect of ovarian activity on orthodontic tooth movement and gingival crevicular fluid levels of interleukin-1beta and prostaglandin E(2) in cats. AB - OBJECTIVE: To evaluate whether there is any correlation between ovarian activity and two potent bone-resorbing mediators (prostaglandin E(2) [PGE(2)], interleukin 1beta [IL-1beta]) secreted from the gingival crevicular fluid (GCF) during orthodontic tooth movement. MATERIALS AND METHODS: Eighteen female cats were included in this study. Animals were randomly divided into three groups (estrous, anestrous, and ovariectomized groups), each having six queens. Estrous was induced by administration of 150 IU equine chorionic gonadotropin (eCG) to queens of the estrous group. A closed-coil spring, applied with 80 g of tipping force to the canine, was attached between the maxillary canine and mini-implant. GCF was collected on days 0, 6, and 12 from each cat to examine PGE(2) and IL-1beta during orthodontic tooth movement in cats. The PGE(2) and IL-1beta levels were determined with enzyme-linked immunosorbent assay. RESULTS: There was no significant difference (P > .05) between anestrous and the ovariectomized groups in terms of tooth movement on days 6 and 12 of distalization. In contrast, tooth movement in the estrous group was lower (P < .05) than in the remaining two groups (anestrous and ovariectomized). The mean PGE(2) and IL-1beta levels of the canine teeth of the estrous groups were significantly lower than the remaining two groups on days 6 and 12 (P < .05) of coil spring applications. CONCLUSIONS: These results indicate that ovarian activity can affect orthodontic tooth movement and GCF levels of IL-1beta and PGE(2) in cats. PMID- 22668315 TI - Three-dimensional airway evaluation in 387 subjects from one university orthodontic clinic using cone beam computed tomography. AB - OBJECTIVE: To determine the linear, volumetric, and cross-sectional area measurements in a large sample of subjects seeking treatment in a university clinic of orthodontics. MATERIALS AND METHODS: Cone-beam computed tomography (CBCT) scans from 387 patients were analyzed retrospectively. All scans were loaded into the 3dMDvultus program (Atlanta, Ga) for airway analysis using automated segmentation. Gender, age, height, weight, airway length, volume, and area of maximum constriction were collected. RESULTS: The rostrocaudal length of the airway increased with age until the age of 15 years in female subjects but continued to increase in male subjects and ranged from 44 to 88 mm over the period of 8 to 18 years of age with the gender data combined. The volume of the airway increased through the entire 11-year age range from 2000 mm(3) to 27,000 mm(3). The rate of airway volume increased at a slower rate in female than in male subjects. The smallest cross-sectional area increased with age ranging from 20 to 250 mm(2) but at a slower rate with female subjects, while male subjects demonstrated a more exponential increase after the age of 13 years. CONCLUSIONS: The human airway increases in length and volume during a rapid period of craniofacial growth in patients between the ages of 8 and 18 years, and the site of maximum cross-sectional area constriction can vary. PMID- 22668316 TI - Direct synthesis of functional azaxanthones by using a domino three-component reaction. AB - NH aldimines, generated in situ from the corresponding aldehydes by reaction with ammonium acetate, serve as nitrogen nucleophiles in reactions with 3-(1 alkynyl)chromones and 3-cyanochromones that generate functionalized azaxanthones. These processes take place under mild conditions that do not require dry solvents. The products of the reactions described represent new chemical entities. We believe that the newly developed cascade process will serve as a potent method for the synthesis of N-heterocycles and in diversity-oriented synthesis. PMID- 22668317 TI - Regulated assembly of the transenvelope protein complex required for lipopolysaccharide export. AB - Gram-negative bacteria are impervious to many drugs and environmental stresses because they possess an outer membrane (OM) containing lipopolysaccharide (LPS). LPS is biosynthesized at the cytoplasmic (inner) membrane and is transported to the OM by an unknown mechanism involving the LPS transport proteins, LptA-G. These proteins have been proposed to form a bridge between the two membranes; however, it is not known how this bridge is assembled to prevent mistargeting of LPS. We use in vivo photo-cross-linking to reveal the specific protein-protein interaction sites that give rise to the Lpt bridge. We also show that the formation of this transenvelope bridge cannot proceed before the correct assembly of the LPS translocon in the OM. This ordered sequence of events may ensure that LPS is never transported to the OM if it cannot be translocated across it to the cell surface. PMID- 22668318 TI - Molecular evidence of Pneumocystis jirovecii reinfection in a haemato-oncology patient. AB - For many years Pneumocystis pneumonia was thought to be caused by the reactivation of a latent infection, but several studies have demonstrated that Pneumocystis jirovecii infection can be acquired de novo. On the basis of our results obtained from a patient with recurrent pneumocystosis, we support the hypothesis that recurrent episodes are caused by reinfection. PMID- 22668319 TI - The right place for the right job in the photovoltaic life cycle. AB - The potential for photovoltaic power generation (PV) to reduce primary energy consumption (PEC) and CO(2) emissions depends on the physical locations of each stage of its life cycle. When stages are optimally located, CO(2) emissions are reduced nearly ten times as much as when each stage is located in the country having the largest current market share. The usage stage contributes the most to reducing CO(2) emissions and PEC, and total CO(2) emissions actually increase when PV is installed in countries having small CO(2) emissions from electricity generation. Global maps of CO(2) reduction potential indicate that Botswana and Gobi in Mongolia are the optimal locations to install PV due to favorable conditions for PV power generation and high CO(2) emissions from current electricity generation. However, the small electricity demand in those countries limits the contribution to global CO(2) reduction. The type of PVs has a small but significant effect on life cycle PEC and CO(2) emissions. PMID- 22668321 TI - Psoriasis treatment patterns with etanercept and adalimumab in a United States health plan population. AB - BACKGROUND: A retrospective study utilizing administrative claims from a US commercial health plan was performed to examine etanercept and adalimumab treatment patterns among patients with psoriasis (PSO). METHODS: Biologic-naive PSO patients initiating etanercept or adalimumab therapy between 18 January 2008 and 31 December 2008 were identified. Patients continuously enrolled in the health plan for 6 months before and >=12 months after therapy initiation were followed until disenrollment from the plan or 31 December 2009. Persistence was defined as continuous use of index TNF blocker without a gap in therapy >=60 days. Patients with gaps in index therapy >=60 days were classified as discontinuing, switching, or restarting the index therapy. RESULTS: In total, 497 patients initiated etanercept and 330 the adalimumab therapy. Mean age for both groups was 43 years. Approximately 40-42% of patients were persistent on their index TNF blocker for 1 year. Among patients with a >=60-day gap in therapy, discontinuation without restart or switch occurred in 37% of etanercept and 45% of adalimumab patients (p = 0.04). Differences in therapy restart or switching between the groups were not statistically significant. CONCLUSIONS: TNF-blocker therapy persistence is low among PSO patients in this health plan. More than one third of patients restarted their index TNF blocker after a gap in therapy. PMID- 22668325 TI - Editorial policy changes. PMID- 22668322 TI - Minor ampullate silks from Nephila and Argiope spiders: tensile properties and microstructural characterization. AB - The mechanical behavior and microstructure of minor ampullate gland silk (miS) of two orb-web spinning species, Argiope trifasciata and Nephila inaurata, were extensively characterized, enabling detailed comparison with other silks. The similarities and differences exhibited by miS when compared with the intensively studied major ampullate gland silk (MAS) and silkworm (Bombyx mori) silk offer a genuine opportunity for testing some of the hypotheses proposed to correlate microstructure and tensile properties in silk. In this work, we show that miSs of different species show similar properties, even when fibers spun by spiders that diverged over 100 million years are compared. The tensile properties of miS are comparable to those of MAS when tested in air, significantly in terms of work to fracture, but differ considerably when tested in water. In particular, miS does not show a supercontraction effect and an associated ground state. In this regard, the behavior of miS in water is similar to that of B. mori silk, and it is shown that the initial elastic modulus of both fibers can be explained using a common model. Intriguingly, the microstructural parameters measured in miS are comparable to those of MAS and considerably different from those found in B. mori. This fact suggests that some critical microstructural information is still missing in our description of silks, and our results suggest that the hydrophilicity of the lateral groups or the large scale organization of the sequences might be routes worth exploring. PMID- 22668326 TI - Washington. PMID- 22668327 TI - International. PMID- 22668328 TI - States. PMID- 22668329 TI - Science. PMID- 22668330 TI - Technology. PMID- 22668331 TI - Business. PMID- 22668332 TI - Spatial concentration distributions. PMID- 22668333 TI - Biological monitoring. PMID- 22668334 TI - Formaldehyde: Assessing the risk. PMID- 22668335 TI - Hazardous waste research. PMID- 22668336 TI - Products. PMID- 22668337 TI - Books & journals catalog. PMID- 22668338 TI - Literature. PMID- 22668339 TI - Guided bone regeneration using injectable vascular endothelial growth factor delivery gel. AB - BACKGROUND: Vascularization underlies the success of guided bone regeneration (GBR) procedures. This study evaluates the regenerative potential of GBR in combination with vascular endothelial growth factor (VEGF) delivery via an injectable hydrogel system. METHODS: Critical-sized defects were created in rat calvariae, and GBR procedures were performed with a collagen membrane alone (control), or plus bolus delivery of VEGF, or plus application of VEGF-releasing hydrogels (VEGF-Alg). Four and 8 weeks after treatment, defect sites were evaluated with microcomputed tomographic and histomorphometric analyses for blood vessel and bone formation. RESULTS: At 4 weeks, relative to the control condition, the bolus addition of VEGF did not affect blood vessel density within the defect site, yet the application of VEGF-Alg significantly (P <0.05) increased blood vessel density. Although there was no difference in bone regeneration at 4 weeks, at 8 weeks there was a significant (P <0.05) increase in bone regeneration in the VEGF-Alg-treated defects. CONCLUSIONS: These data demonstrate that the application of VEGF-Alg enhanced early angiogenesis, whereas at a later time point, it enhanced bone regeneration. Controlled delivery approaches of angiogenic growth factors used adjunctively with GBR may be a promising strategy for enhancing outcomes of GBR. PMID- 22668341 TI - Thermochemistry and bond dissociation energies of ketones. AB - Ketones are a major class of organic chemicals and solvents, which contribute to hydrocarbon sources in the atmosphere, and are important intermediates in the oxidation and combustion of hydrocarbons and biofuels. Their stability, thermochemical properties, and chemical kinetics are important to understanding their reaction paths and their role as intermediates in combustion processes and in atmospheric chemistry. In this study, enthalpies (DeltaH degrees (f 298)), entropies (S degrees (T)), heat capacities (C(p) degrees (T)), and internal rotor potentials are reported for 2-butanone, 3-pentanone, 2-pentanone, 3-methyl-2 butanone, and 2-methyl-3-pentanone, and their radicals corresponding to loss of hydrogen atoms. A detailed evaluation of the carbon-hydrogen bond dissociation energies (C-H BDEs) is also performed for the parent ketones for the first time. Standard enthalpies of formation and bond energies are calculated at the B3LYP/6 31G(d,p), B3LYP/6-311G(2d,2p), CBS-QB3, and G3MP2B3 levels of theory using isodesmic reactions to minimize calculation errors. Structures, moments of inertia, vibrational frequencies, and internal rotor potentials are calculated at the B3LYP/6-31G(d,p) density functional level and are used to determine the entropies and heat capacities. The recommended ideal gas-phase DeltaH degrees (f 298), from the average of the CBS-QB3 and G3MP2B3 levels of theory, as well as the calculated values for entropy and heat capacity are shown to compare well with the available experimental data for the parent ketones. Bond energies for primary, secondary, and tertiary radicals are determined; here, we find the C-H BDEs on carbons in the alpha position to the ketone group decrease significantly with increasing substitution on these alpha carbons. Group additivity and hydrogen-bond increment values for these ketone radicals are also determined. PMID- 22668342 TI - Density functional theory investigation of the redox properties of tricyclopentadienyl- and phospholyluranium(IV) chloride complexes. AB - The redox behavior of tricyclopentadienyl- and phospholyluranium(IV) chloride complexes L(3)UCl with L = C(5)H(5) (Cp), C(5)H(4)Me (MeCp), C(5)H(4)SiMe(3) (TMSCp), C(5)H(4)(t)Bu ((t)BuCp), C(5)Me(5) (Cp*), and C(4)Me(4)P (tmp), has been investigated using relativistic density functional theory calculations, with the solvent being taken into account using the conductor-like screening model. A very good linear correlation (r(2) = 0.99) has been obtained between the computed electron affinities of the L(3)UCl complexes and the experimental half-wave reduction potentials E(1/2) related to the U(IV)/U(III) redox systems. From a computational point of view, our study confirms the crucial importance of spin orbit coupling and solvent corrections and the use of an extended basis set in order to achieve the best experiment-theory agreement. Considering oxidation of the uranium(IV) complexes, the instability of the uranium(V) derivatives [L(3)UCl](+) is revealed, in agreement with experimental electrochemical findings. The driving roles of both the electron-donating ability of the L ligand and the U 5f orbitals on the redox properties of the complexes are brought to light. Interestingly, we found and explained the excellent correlation between variations of the uranium Hirschfeld charges following U(IV)/U(III) electron capture and E(1/2). In addition, this work allowed one to estimate theoretically the half-wave reduction potential of [Cp*(3)UCl]. PMID- 22668343 TI - Separation of nanoparticles in aqueous multiphase systems through centrifugation. AB - This paper demonstrates the use of aqueous multiphase systems (MuPSs) as media for rate-zonal centrifugation to separate nanoparticles of different shapes and sizes. The properties of MuPSs do not change with time or during centrifugation; this stability facilitates sample collection after separation. A three-phase system demonstrates the separation of the reaction products (nanorods, nanospheres, and large particles) of a synthesis of gold nanorods, and enriches the nanorods from 48 to 99% in less than ten minutes using a benchtop centrifuge. PMID- 22668344 TI - Facial nerve aberrations encountered during cochlear implantation. AB - CONCLUSION: In patients with cochleovestibular malformations, surgeons should always consider the possibility of an aberrant course or shape of the facial nerve (FN). In our series, the majority of cases could be successfully implanted without major complications through careful handling of the FN and ossicles. OBJECTIVES: To assess the frequency, type, and surgical implications of FN aberrations encountered during cochlear implantation (CI). METHODS: Medical records and radiologic findings of 972 patients who underwent CI from 1988 to 2009 were reviewed retrospectively. Radiologic and intraoperative findings demonstrating malformations of the FN, ossicles, and inner ear were evaluated. Intraoperative events and postoperative FN outcome were reviewed. RESULTS: Seven patients (0.7%) had an aberrant course or shape of the FN during CI. All these patients were pediatric. Four showed abnormal anterior or inferior location of the vertical segment, two had a bifurcated horizontal or vertical segment, and one had an inferiorly located horizontal segment. All seven patients displayed combined malformations of the cochlea and had malformed or missing ossicles. CIs were successfully performed via the facial recess approach and cochleostomy. There was no postoperative FN paralysis except in one case with immediate iatrogenic FN paralysis that recovered completely 1 month after FN decompression. PMID- 22668340 TI - Effect of diabetes mellitus on pharmacokinetic and pharmacodynamic properties of drugs. AB - The effects of diabetes mellitus on the pharmacokinetics and pharmacodynamics of drugs have been well described in experimental animal models; however, only minimal data exist for humans and the current knowledge regarding the effects of diabetes on these properties remains unclear. Nevertheless, it has been observed that the pharmacokinetics and pharmacodynamics of drugs are changed in subjects with diabetes. It has been reported that diabetes may affect the pharmacokinetics of various drugs by affecting (i) absorption, due to changes in subcutaneous adipose blood flow, muscle blood flow and gastric emptying; (ii) distribution, due to non-enzymatic glycation of albumin; (iii) biotransformation, due to regulation of enzymes/transporters involved in drug biotransformation; and (iv) excretion, due to nephropathy. Previously published data also suggest that diabetes-mediated changes in the pharmacokinetics of a particular drug cannot be translated to others. Although clinical studies exploring the effect of diabetes on pharmacodynamics are still very limited, there is evidence that disease mediated effects are not limited only to pharmacokinetics but also alter pharmacodynamics. However, for many drugs it remains unclear whether these influences reflect diabetes-mediated changes in pharmacokinetics rather than pharmacodynamics. In addition, even though diabetes-mediated pharmacokinetics and pharmacodynamics might be anticipated, it is important to study the effect on each drug and not generalize from observed data. The available data indicate that there is a significant variability in drug response in diabetic subjects. The discrepancies between individual clinical studies as well as between ex vivo and clinical studies are probably due to (i) the restricted and focused population of subjects in clinical studies; (ii) failure to consider type, severity and duration of the disease; (iii) histopathological characteristics generally being missing; and (iv) other factors such as varying medication use, dietary protein intake, age, sex and obesity. The obesity epidemic in the developed world has also inadvertently influenced the directions of pharmacological research. This review attempts to map new information gained since Gwilt published his paper in Clinical Pharmacokinetics in 1991. Although a large body of research has been conducted and significant progress has been made, we still have to conclude that the available information regarding the effect of diabetes on pharmacokinetics and pharmacodynamics remains unclear and further clinical studies are required before we can understand the clinical significance of the effect. An understanding of diabetes-mediated changes as well as of the source of the variability should lead to the improvement of the medical management and clinical outcomes in patients with this widespread disease. PMID- 22668345 TI - Intraoperative CT-guided cochlear implantation in congenital ear deformity. AB - CONCLUSIONS: Intraoperative computed tomography (iCT)-guided cochlear implantation is practical and effective for correct electrode placement in the cochlea of patients with congenital inner ear and/or complex middle ear malformation. OBJECTIVES: The operation in patients with inner ear and/or complex middle ear malformation including abnormal facial nerve course is difficult. This study evaluated the efficacy of cochlear implantation under the guidance of iCT to insure correct electrode placement. METHODS: This was a prospective interventional case series. Ten patients with severe to profound sensorineural hearing loss due to ear malformations were enrolled, and iCT was used to confirm the right placement of electrodes. RESULTS: Intraoperative CT was performed three times in one patient, twice in two, and once in the others. Interruption of the surgical process for each iCT until resumption of surgery was 9.64 +/- 0.63 min. iCT revealed incorrectly positioned cochlear implants in two patients, which were immediately corrected. There were no reoperations due to misplacement of electrodes. iCT helped locate the cochlea in the middle ear of one patient with an abnormal facial nerve course. The overall intervention rate based on iCT findings was 30%. LEVEL OF EVIDENCE: level 4. PMID- 22668346 TI - Microarray analysis and biochemical correlations of oxidative stress responsive genes in retinoblastoma. AB - PURPOSE: Oxidative stress, which refers to the biological damage caused by free radicals produced in excess of innate antioxidant defenses, is indicated in the ocular cancer retinoblastoma (RB). Here we have analysed the differential expression of oxidative stress responsive genes in oxidant-induced RB cells, and in RB tumor tissues. METHODS: The study included cultured RB cells, and four RB tumor tissues. The reactive oxygen species (ROS) levels in Y79 cells and the RB tumor induced by hydrogen peroxide were quantified by Dichlorofluorescein (DCF) fluorescence assay. We then analysed the gene expression profile of cultured RB cells induced with hydrogen peroxide (400 uM H(2)O(2) for 8 h) by microarray analysis, and the expression of select genes were validated in Y79 cells and RB tumor tissues by real-time PCR analysis. RESULTS: The oxidant-induced RB tumors showed an average increase in ROS levels of 44-fold compared to induced non neoplastic donor retina. H(2)O(2)-induced RB cell line showed a 3-fold increase in ROS levels. Microarray analysis on RB cell line induced with H(2)O(2) showed differentially regulated genes involved in cellular processes such as: oxidative stress, angiogenesis, lipid metabolism, cell proliferation, and cell signaling pathways. Several up-regulated genes such as SOD, GPX, CAT, CDC25A, CREBBP, JUN, MMP-2, iNOS, CRYAA, RXRA, ACACB and HMGCR were validated by real-time PCR. These results corroborated with the gene expression analysis in RB tumor tissues. Relating the antioxidant gene expression with the clinico-pathologic features of the tumor tissues, we found that the tumor with invasion of choroid, optic nerve and retinal pigment epithelium, had relatively higher ROS levels and minimal antioxidant gene expression, when compared with the tumor with only choroidal invasion. CONCLUSIONS: The study suggests active involvement of redox signaling pathways in the pathogenesis of RB. Consideration of oxidative stress components in the clinical management of RB patients is emphasized. PMID- 22668347 TI - Conjunctival microbial florae in patients with seriously sulfur mustard induced eye injuries. AB - INTRODUCTION: Ocular surface disorders and infections in sulfur mustard (SM) exposed patients are of particular clinical importance. The aim of the present study is to detect the conjunctival bacterial florae in patients with seriously SM induced eye injuries. MATERIALS AND METHODS: Conjunctival bacterial florae of 143 seriously eye injured subjects as the study group was detected. The results were compared with 26 normal participants. Both groups were matched in age and sex. The samples were taken by sterile swab from interior fornixes of conjunctiva in both groups and were transported to microbiology laboratory by Stuart's Transport Medium. All samples were inoculated onto Blood agar, Mac Conkey agar and Chocolate agar and isolated microorganisms were identified by biochemical tests. The data were analyzed by SPSS and Man Whitney tests. RESULTS: Nineteen cases (13.39%) and none of the controls (0%) had positive culture results (p = .043). Isolated microorganisms from patients included coagulase-negative staphylococci 10 cases (52.6%), Staphylococcus aureus 5 cases (26.3%), non enterobacteriaceae gram negative bacilli 2 cases (10.5%), Penicillium spp. 2 cases (10.5%), Citrobacter sp. 1 case (5.2%), non-spore forming Gram positive bacillus 1 case (5.2%) and alpha hemolytic streptococcus 1 case (5.2%). Two patients had mixed microorganisms and other patients had just one microorganism. Most of the S. aureus isolates were sensitive to usual antibiotics. CONCLUSIONS: The results of this study showed that the prevalence rate of conjunctival bacterial isolates in patients with seriously SM induced ocular injuries are higher and potentially more dangerous than normal controls. PMID- 22668348 TI - Unexpected copper-catalyzed aerobic oxidative cleavage of C(sp3)-C(sp3) bond of glycol ethers. AB - An unexpected Cu-catalyzed oxidative cleavage of the C(sp(3))-C(sp(3)) bond in glycol ethers by using air or molecular oxygen as the terminal stoichiometric oxidant is demonstrated. As a result, the corresponding alpha-acyloxy ethers and formates of 1,2-ethanediol are formed by direct coupling of carboxylic acids and aldehydes with glycol ethers under the reaction conditions. This method represents the first example of Cu-catalyzed aerobic cleavage of saturated C-C bond in ethers. PMID- 22668349 TI - Impact of oncogenic driver mutations on feedback between the PI3K and MEK pathways in cancer cells. AB - Inhibition of the PI3K (phosphoinositide 3-kinase)/Akt/mTORC1 (mammalian target of rapamycin complex 1) and Ras/MEK [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase]/ERK pathways for cancer therapy has been pursued for over a decade with limited success. Emerging data have indicated that only discrete subsets of cancer patients have favourable responses to these inhibitors. This is due to genetic mutations that confer drug insensitivity and compensatory mechanisms. Therefore understanding of the feedback mechanisms that occur with respect to specific genetic mutations may aid identification of novel biomarkers that predict patient response. In the present paper, we show that feedback between the PI3K/Akt/mTORC1 and Ras/MEK/ERK pathways is cell-line-specific and highly dependent on the activating mutation of K-Ras or overexpression c-Met. We found that cell lines exhibited differential signalling and apoptotic responses to PD184352, a specific MEK inhibitor, and PI103, a second-generation class I PI3K inhibitor. We reveal that feedback from the PI3K/Akt/mTORC1 to the Ras/MEK/ERK pathway is present in cancer cells harbouring either K-Ras activating mutations or amplification of c-Met but not the wild-type counterparts. Moreover, we demonstrate that inhibition of protein phosphatase activity by OA (okadaic acid) restored PI103-mediated feedback in wild-type cells. Together, our results demonstrate a novel mechanism for feedback between the PI3K/Akt/mTORC1 and the Ras/MEK/ERK pathways that only occurs in K-Ras mutant and c-Met amplified cells but not the isogenic wild-type cells through a mechanism that may involve inhibition of a specific endogenous phosphatase(s) activity. We conclude that monitoring K-Ras and c-Met status are important biomarkers for determining the efficacy of PI103 and other PI3K/Akt inhibitors in cancer therapy. PMID- 22668350 TI - ABC transporters and immunity: mechanism of self-defense. AB - The transporter associated with antigen processing (TAP) is a prototype of an asymmetric ATP-binding cassette (ABC) transporter, which uses ATP binding and hydrolysis to translocate peptides from the cytosol to the lumen of the endoplasmic reticulum (ER). Here, we review molecular details of peptide binding and ATP binding and hydrolysis as well as the resulting allosteric cross-talk between the nucleotide-binding domains and the transmembrane domains that drive translocation of the solute across the ER membrane. We also discuss the general molecular architecture of ABC transporters and demonstrate the importance of structural and functional studies for a better understanding of the role of the noncanonical site of asymmetric ABC transporters. Several aspects of peptide binding and specificity illustrate details of peptide translocation by TAP. Furthermore, this ABC transporter forms the central part of the major histocompatibility complex class I (MHC I) peptide-loading machinery. Hence, TAP is confronted with a number of viral factors, which prevent antigen translocation and MHC I loading in virally infected cells. We review how these viral factors have been used as molecular tools to decipher mechanistic aspects of solute translocation and discuss how they can help in the structural analysis of TAP. PMID- 22668351 TI - Polarons, bipolarons, and side-by-side polarons in reduction of oligofluorenes. AB - The nature of charge carriers in conjugated polymers was elucidated through optical spectroscopy following single- and multielectron reduction of 2,7-(9,9 dihexylfluorene) oligomers, F(n), n = 1-10, yielding spectra with the two bands typical of polarons upon single reduction. For short oligomers addition of a second electron gave a single band demonstrating the classic polaron-bipolaron transition. However, for long oligomers double reductions yielded spectra with two bands, better described as two polarons, possibly residing side-by-side in the F(n) chains. The singly reduced anions do not appear to delocalize over the entire length of the longer conjugated systems; instead they are polarons occupying approximately four fluorene repeat units. The polarons of F(3) and F(4) display sharp absorption bands, but for longer oligomers the bands broaden, possibly due to fluctuations of the lengths of these unconfined polarons. DFT calculations with long-range-corrected functionals were fully consistent with the experiments describing polarons in anions, bipolarons in dianions of short oligomers, and side-by-side polarons in dianions of long oligomers, while results from standard functionals were not compatible with the experimental results. The computations found F(10)(2-), for example, to be an open-shell singlet ( ~ 1), with electrons in two side-by-side orbitals, while dianions of shorter oligomers experienced a gradual transition to bipolarons with states of intermediate character at intermediate lengths. The energies and extinction coefficients of each anionic species were measured by ultraviolet-visible-near infrared absorption spectroscopy with chemical reduction and pulse radiolysis. Reduction potentials determined from equilibria mirrored oxidation potentials reported by Chi and Wegner. Anions of oligomers four or more units in length contained vestigial neutral (VN) absorption bands that arise from neutral parts of the chain. Energies of the VN bands correspond to those of oligomers shorter by four units. PMID- 22668407 TI - Synthesis, structure, electrochemistry, and electrochemiluminescence of thienyltriazoles. AB - Four blue-emitting thienyltriazoles with desired N and O coordination atoms were prepared in high yield via click chemistry for potential incorporation into metal complexes. Three of their crystal structures were determined by X-ray crystallography. The electrochemical properties, electronic structures of these thienyltriazoles, 1-4, and their correlations were studied using cyclic voltammetry and differential pulse voltammetry techniques along with density function theory (DFT) calculations. All of the compounds underwent irreversible redox reactions, leading to unstable electrogenerated radical cations and anions. Electrochemical gaps determined from the differences between first formal reduction and oxidation reactions were correlated to HOMO-LUMO energy gaps obtained from UV-vis spectroscopy and the DFT calculations as well as energies of excited states measured from photoluminescence spectroscopy. We observed weak electrochemiluminescence (ECL) from annihilation of these thienyltriazole radicals in acetonitrile containing 0.1 M tetra-n-butylammonium perchlorate as electrolyte. An enhancement in ECL efficiency ranging from 0.16 to 0.50% was observed upon addition of benzoyl peroxide as a coreactant in the above electrolyte solutions. The generation of excimers in solutions of 1-4 was observed as seen by the red-shift in ECL maxima relative to their corresponding photoluminescence peak wavelengths. Our work is of importance for the development of efficient blue-emitting fluorophores via click chemistry that could be potential luminophores in metal complexes. PMID- 22668408 TI - Methods in 2012. PMID- 22668411 TI - Building with biological LEGO. Interview by Kristie Nybo. PMID- 22668413 TI - RNAi therapeutics: the teenage years. PMID- 22668414 TI - GFP imaging in fixed cells. PMID- 22668415 TI - Isolation and culture of primary osteocytes from the long bones of skeletally mature and aged mice. AB - The purpose of this work was to establish a methodology to enable the isolation and study of osteocytes from skeletally mature young (4-month-old) and old (22 month-old) mice. The location of osteocytes deep within bone is ideal for their function as mechanosensors. However, this location makes the observation and study of osteocytes in vivo technically difficult. Osteocytes were isolated from murine long bones through a process of extended collagenase digestions combined with EDTA-based decalcification. A tissue homogenizer was used to reduce the remaining bone fragments to a suspension of bone particles, which were placed in culture to yield an outgrowth of osteocyte-like cells. All of the cells obtained from this outgrowth that displayed an osteocyte-like morphology stained positive for the osteocyte marker E11/GP38. The osteocyte phenotype was further confirmed by a lack of staining for alkaline phosphatase and the absence of collagen1a1 expression. The outgrowth of osteocytes also expressed additional osteocyte specific genes such as Sost and Mepe. This technique facilitates the isolation of osteocytes from skeletally mature bone. This novel enabling methodology should prove useful in advancing our understanding of the roles mature osteocytes play in bone health and disease. PMID- 22668416 TI - Creation and application of immortalized bait libraries for targeted enrichment and next-generation sequencing. AB - Since the introduction of next-generation sequencing, several techniques have been developed to selectively enrich and sequence specific parts of the genome at high coverage. These techniques include enzymatic methods employing molecular inversion probes, PCR based approaches, hybrid capture, and in-solution capture. In-solution capture employs RNA probes transcribed from a pool of DNA template oligos designed to match regions of interest to specifically bind and enrich genomic DNA fragments. This method is highly efficient, especially if genomic target regions are large in size or quantity. Diverse in-solution capture kits are available, but are costly when large sample numbers need to be analyzed. Here we present a cost-effective strategy for the design of custom DNA libraries, their transcription into RNA libraries, and application for in-solution capture. We show the efficacy by comparing the method to a commercial kit and further demonstrate that emulsion PCR can be used for bias free amplification and virtual immortalization of DNA template libraries. PMID- 22668417 TI - Trehalose-enhanced isolation of neuronal sub-types from adult mouse brain. AB - Efficient isolation of specific, intact, living neurons from the adult brain is problematic due to the complex nature of the extracellular matrix consolidating the neuronal network. Here, we present significant improvements to the protocol for isolation of pure populations of neurons from mature postnatal mouse brain using fluorescence activated cell sorting (FACS). The 10-fold increase in cell yield enables cell-specific transcriptome analysis by protocols such as nanoCAGE and RNA seq. PMID- 22668418 TI - Coding SNPs as intrinsic markers for sample tracking in large-scale transcriptome studies. AB - Large-scale transcriptome profiling in clinical studies often involves assaying multiple samples of a patient to monitor disease progression, treatment effect, and host response in multiple tissues. Such profiling is prone to human error, which often results in mislabeled samples. Here, we present a method to detect mislabeled sample outliers using coding single nucleotide polymorphisms (cSNPs) specifically designed on the microarray and demonstrate that the mislabeled samples can be efficiently identified by either simple clustering of allele specific expression scores or Mahalanobis distance-based outlier detection method. Based on our results, we recommend the incorporation of cSNPs into future transcriptome array designs as intrinsic markers for sample tracking. PMID- 22668419 TI - Open-sandwich molecular imprinting: making a recognition matrix with antigen imprinted antibody fragments. AB - A novel antibody-polymer conjugation method termed open-sandwich molecular imprinting (OS-MIP) has been proposed to produce a specific recognition matrix in the presence of a target antigen. The resultant carboxymethyldextran matrix conjugated with two separate antibody variable region fragments imprinted with the cognate antigen showed higher antigen-binding capacity than non-imprinted ones and was successfully used to sensitively monitor multiple antigen binding/desorption events by a surface plasmon resonance biosensor. Furthermore, when each fragment was labeled with different fluorophores before conjugation, the fluorescence signals of the matrix made by OS-MIP clearly showed an antigen concentration dependent increase in Forster resonance energy transfer between the two dyes. By using a combination of various methods for detecting interaction, OS MIP will be a useful platform for detecting various targets from small molecules to proteins with high sensitivity and specificity. PMID- 22668421 TI - Hard and soft acids and bases: structure and process. AB - Under investigation is the structure and process that gives rise to hard-soft behavior in simple anionic atomic bases. That for simple atomic bases the chemical hardness is expected to be the only extrinsic component of acid-base strength, has been substantiated in the current study. A thermochemically based operational scale of chemical hardness was used to identify the structure within anionic atomic bases that is responsible for chemical hardness. The base's responding electrons have been identified as the structure, and the relaxation that occurs during charge transfer has been identified as the process giving rise to hard-soft behavior. This is in contrast the commonly accepted explanations that attribute hard-soft behavior to varying degrees of electrostatic and covalent contributions to the acid-base interaction. The ability of the atomic ion's responding electrons to cause hard-soft behavior has been assessed by examining the correlation of the estimated relaxation energies of the responding electrons with the operational chemical hardness. It has been demonstrated that the responding electrons are able to give rise to hard-soft behavior in simple anionic bases. PMID- 22668422 TI - How does the tennis serve technique influence the serve-and-volley? AB - In tennis, a high ball velocity and a fast run toward the net are key features to successful performance of "serve-and-volley" players. For the serve, tennis players can use two techniques: the foot-up (FU) or foot-back (FB) technique. The aim of this study was to determine if the running time toward the net after the serve and the ball velocity (V(ball)) vary between these two techniques. Moreover we analysed the angular momentum values of the trunk and of the arm holding the racquet. Fifteen expert tennis players performed six successful serve-and-volleys with both techniques. Running time to the net is significantly lower for FB, whereas V(ball) is significantly higher for FU. Trunk and arm angular momentums about the transverse axis are significantly higher with FU before ball impact. A significant correlation (r = 0.81, P < 0.001) exists between changes in the maximal trunk angular momentum and in running time to the net between the two serve techniques. A significant correlation (r = 0.84, P < 0.001) also exists between changes in the maximal trunk angular momentum and in V(ball) between the two serve techniques. According to these results, FB is the best technique for moving as quickly as possible to the net because of a lower trunk angular momentum. PMID- 22668424 TI - The therapeutic effects of anticonvulsants in the treatment of orofacial pain. PMID- 22668425 TI - Beyond warfarin: the new generation of oral anticoagulants and their implications for the management of dental patients. AB - Warfarin has been the primary anticoagulant drug used in the USA for more than 50 years. However, 2 novel types of oral anticoagulants have recently been approved for use in the USA. These are direct thrombin inhibitors (e.g., dabigatran etexilate) and factor Xa inhibitors (e.g., rivaroxaban). Dental health care providers may soon encounter patients who are being prescribed these medications. This article describes the pharmacologic properties and medical uses of these new oral anticoagulants. Also discussed are implications for the management of dental patients being treated with these new oral anticoagulants, including potential interactions with drugs commonly used or prescribed in the course of dental treatment. PMID- 22668426 TI - Lesion presenting as an expanding mass of the palate. PMID- 22668427 TI - Clinical evaluation of allicin oral adhesive tablets in the treatment of recurrent aphthous ulceration. AB - OBJECTIVE: We investigated the effectiveness and safety of topical application of 5 mg allicin adhesive tablets in the treatment of minor recurrent aphthous ulcerations (MiRAU). MATERIAL AND METHODS: A randomized, double-blinded, placebo controlled, clinical trial was performed. Tablets containing 5 mg allicin or vehicle only were consecutively applied 4 times per day for 5 days. The size and pain level of ulcers were measured and recorded on days 1, 2, 4, and 6. RESULTS: A total of 96 subjects with MiRAU fulfilled the study. Allicin adhesive tablets significantly reduced ulcer size (P < .005, P < .003, P < .001 for days 2, 4, and 6, respectively) and alleviated ulcer pain score (P < .03, P < .001, P < .05 for days 2, 4, and 6, respectively) compared with vehicle tablets. Minor and major adverse reactions were not observed. CONCLUSIONS: Allicin adhesive tablets were effective in reducing ulcer size and alleviating ulcer pain of the patients in the treatment of MiRAU without significant side effects. PMID- 22668428 TI - Hospital-based emergency department visits with herpetic gingivostomatitis in the United States. AB - OBJECTIVES: The objectives of this study were to determine the number of hospital emergency department (ED) visits with a diagnosis of herpetic gingivostomatitis (HGS) for 2007 in the United States and to identify the possible comorbid conditions associated with HGS. STUDY DESIGN: The Nationwide Emergency Department Sample for 2007 was used in this study. Patients who visited the ED with a diagnosis of HGS were selected. Estimates were projected to the national levels using the discharge weights. Presence of comorbid conditions in these patients was also analyzed. RESULTS: A total of 23,124 patients had ED visits and received the diagnosis of HGS. Most of the patients were young females and those belonging to the lower socioeconomic strata. All patients with HGS also presented with comorbid conditions. CONCLUSIONS: Physicians should be trained to diagnose, manage, and refer common dental emergencies. In the long term, improving access to dental care for these patients is crucial to managing this problem. PMID- 22668429 TI - Effects of eating disorders on oral fungal diversity. AB - BACKGROUND: The eating disorders anorexia and bulimia nervosa can cause several systemic and oral alterations related to poor nutrition and induced vomiting; however, the oral microflora of these patients is poorly studied. OBJECTIVE: The aim of this study was to evaluate fungal microflora in the oral cavity of these patients by culture-dependent and culture-independent methods. STUDY DESIGN: Oral rinse samples were cultured to assess the prevalence of Candida species, and the isolates were identified by API system. Microorganism counts were compared by the Mann-Whitney test (5%). Ribotyping, a type of molecular analysis, was performed by sequencing the D1/D2 regions of 28S rRNA. RESULTS: Our results demonstrated that the eating disorder group showed higher oral Candida spp. prevalence with culture-dependent methods and higher species diversity with culture-independent methods. CONCLUSIONS: Eating disorders can lead to an increased oral Candida carriage. Culture-independent identification found greater fungal diversity than culture-dependent methods. PMID- 22668430 TI - Clinical and histopathologic parameters in survival of oral squamous cell carcinoma. AB - OBJECTIVE: The aim of this study was to assess the relevance of clinical and histopathologic parameters on survival of oral squamous cell carcinoma (OSCC) patients in Sri Lanka. STUDY DESIGN: A cohort of 193 previously diagnosed OSCC patients were followed for up to 5 years. Clinical and histopathologic parameters were analyzed regarding local recurrence and 5-year survival after treatment. RESULTS: Site, stage, local recurrence, degree of differentiation, degree of keratinization, pattern of invasion, and status of the excision margins showed a significant association with the 5-year survival (P < .05). Multivariate analysis identified stage, pattern of invasion, and status of the excision margins as true independent prognostic indicators of OSCC. Pattern of invasion was the best prognosticator of both local recurrence and overall survival in the Cox regression model (P < .001). CONCLUSIONS: Stage, pattern of invasion, and status of the excision margins are superior prognostic indicators of OSCC compared with other parameters. PMID- 22668431 TI - Marginal zone lymphoma of mucosa-associated lymphoid tissue with prominent plasma cell differentiation affecting the palatine tonsil: histopathological and immunohistochemical analysis. AB - Non-Hodgkin lymphomas (NHLs) of the oral cavity and oropharynx constitute 13% of all primary extranodal NHLs. Marginal zone B-cell lymphoma of the mucosa associated lymphoid tissue (MALT lymphoma) in the palatine tonsil is rare, corresponding to 6% of the NHLs of the Waldeyer ring. Some cases of MALT lymphoma can present prominent plasma cell differentiation, and less commonly, monoclonal gammopathy. The differential diagnosis of these cases from other NHLs with plasmacytic differentiation or plasma cell neoplasms is very difficult. In this article, we describe a rare case of MALT lymphoma in a 34-year-old man presenting as a swelling of the palatine tonsil. The tumor mass was diagnosed as MALT lymphoma with prominent plasma cell differentiation. Systemic evaluation was noncontributory. This is the first report of MALT lymphoma showing extensive plasmacytic differentiation of the palatine tonsil, and reinforces a possible relationship between extramedullary plasmacytoma and MALT lymphoma. PMID- 22668432 TI - Immunolocalization of bone morphogenetic protein 2 during the early healing events after guided bone regeneration. AB - OBJECTIVE: The objective of this study was to evaluate the immunolocalization of bone morphogenetic protein 2 (BMP-2) after autogenous block grafting covered or not with an e-PTFE membrane. STUDY DESIGN: Forty-eight rats were divided into 2 groups, autogenous block graft (B) and autogenous block graft + e-PTFE membrane (MB), and were evaluated by immunohistochemistry at baseline and 3, 7, 14, 21, and 45 days. RESULTS: The largest number of positive cells in the recipient bed was observed after 3 days in both groups. At the graft border, the largest number of positive cells was seen after 7 days in group B and after 14 days in group MB. The highest proportion of staining in the graft was observed after 3 days in group B and after 21 days in group MB. CONCLUSIONS: High proportions of stain were related to intense revascularization and osteogenesis. Except for the interface, BMP-2 staining occurred later in group MB than in group B in all structures analyzed. PMID- 22668433 TI - Evaluation of alveolar bone grafting using limited cone beam computed tomography. AB - OBJECTIVE: The objective of this study was to evaluate the bone resorption of alveolar bone grafting using LCBCT scan. STUDY DESIGN: This was a prospective study. Nineteen patients with alveolar cleft were divided into 2 groups depending on the spontaneous eruption of the permanent tooth. All patients underwent alveolar bone grafting with iliac crest cancellous bone. LCBCT scans were taken 1 month and 6 months postoperatively. RESULTS: LCBCT scans obtained the length, width, and height of the bone grafts. Three-dimensional (3D) reconstruction of the bone grafts enabled a valuable objective assessment of the graft volume. The resorption ratio was 10.4% when the permanent tooth erupted spontaneously into the graft. In the group with absence of the permanent tooth, the resorption ratio was 36.6%. CONCLUSION: LCBCT scan and 3D reconstruction is a promising method for evaluation of the outcome of alveolar bone grafts. Bone grafts showed a high grade of resorption in patients lacking permanent tooth eruption. PMID- 22668434 TI - Recursive hierarchic segmentation analysis of bone mineral density changes on digital panoramic images. AB - OBJECTIVE: The aim of this study was to demonstrate that histogram analysis and mathematical modeling of digital panoramic images (DPIs) processed using recursive hierarchic segmentation (RHSEG) discriminates normal, osteopenic, and osteoporotic cancellous bone. STUDY DESIGN: Forty-seven DPIs of postmenopausal women were grouped into normal, osteopenic, and osteoporotic; dual-energy x-ray absorptiometry was the reference standard. RHSEG of the mandibular angle and canine/premolar trabecular regions of interest was performed. After histogram and histogram bin analysis and generation of relative intensity functions, generalized linear mixed model analysis was used to model the data and likelihood ratio testing used to assess group differences. RESULTS: Histogram analyses discriminated among the groups. Receiver operating characteristic analysis of the canine/premolar data yielded area-under-the-curve accuracies of 0.78 for osteoporosis and 0.74 for osteopenia. Discrimination of osteoporosis required cubic analysis, discrimination of osteopenia required quartic analysis, and neither model alone discriminated among all groups. CONCLUSIONS: Analyses and mathematical modeling of mandibular trabecular bone on RHSEG-processed DPIs discriminated normal, osteoporotic, and osteopenic patients. PMID- 22668435 TI - Magnetic resonance angiography with fresh blood imaging for identification of hemangiomas and blood vessels around hemangiomas in oral and maxillofacial regions. AB - OBJECTIVES: To evaluate fresh blood imaging (FBI), a magnetic resonance imaging technique that does not use contrast, for identifying hemangiomas and feeding arteries in the oral and maxillofacial regions. STUDY DESIGN: For 16 patients with hemangiomas, FBI visualizations of hemangiomas and feeding arteries in the oral and maxillofacial regions were compared with those from 3-dimensional (3D) phase-contrast magnetic resonance angiography (PC-MRA). Comparisons were based on the conspicuities of blood vessels and the 3D relationships of hemangiomas with the surrounding blood vessels. RESULTS: The conspicuity of hemangiomas, feeding arteries, and blood vessels were significantly better with FBI than with PC-MRA. After differentiating arteries from veins, 3D visualizations of hemangiomas and arteries or veins could be performed with FBI. CONCLUSIONS: FBI is a useful method in oral and maxillofacial regions for identifying the relationships between hemangiomas and the surrounding arteries or veins. PMID- 22668437 TI - Recurrent keratocystic odontogenic tumor in the masseter muscle overlying the boney perforations: a case report. AB - Keratocystic odontogenic tumor (KCOT) is a benign intraosseous neoplasm of odontogenic origin with high recurrence rates and tendency to invade adjacent tissue. Most recurrences occur in the first 5 years after surgery and are usually located at the site of the primary tumor in the jaws. We report a rare case of KCOT which recurred in the masseter muscle 14 years after segmental mandibulectomy and autogenous frozen lesional mandible reimplantation. The patient had undergone enucleation of KCOT in the right mandible 20 years before segmental mandibulectomy. This case could further demonstrate the aggressive behavior of KCOT. PMID- 22668438 TI - Orofacial granulomatosis: clinical study of 20 patients. AB - OBJECTIVES: The objective of this study was to analyze the clinical features of a series of patients with orofacial granulomatosis (OFG). STUDY DESIGN: Twenty patients diagnosed with OFG at Bellvitge Hospital (Barcelona, Spain) from 1985 to 2010 were included in the study. RESULTS: All of our patients (9 men and 11 women, median age 48.1 years) presented with labial swelling. Six patients presented with recurrent orofacial swelling, 12 with permanent swelling, and 2 with progressive swelling. Fissured tongue was observed in 9 cases, and 2 patients presented with recurrent episodes of peripheral facial paralysis. The median follow-up time was 65.1 months, ranging from 4 to 300 months. None of our patients developed sarcoidosis or Crohn disease. CONCLUSIONS: In the south of Europe, OFG does not appear to be as frequently associated with Crohn disease as in northern Europe. Although several treatments may achieve transient control of the orofacial swelling, there is no curative treatment for OFG and some patients may develop embarrassing lesions. PMID- 22668440 TI - Proceedings of the Dengue Congress at the 9th International Congress of Tropical Pediatrics in Bangkok in October 2011. PMID- 22668439 TI - Resolution of pain and complete healing of mandibular osteoradionecrosis using pentoxifylline and tocopherol: a case report. AB - The radiation-induced fibroatrophic process (RIF) is a time-dependent adverse sequela to high-dose radiotherapy that can result in irreversible tissue death and bone exposure in the irradiated tissue. Osteoradionecrosis (ORN) is a late effect of RIF, described as bony exposure present for more than 3 months that can occur in 20% of patients irradiated for head and neck cancer. The intractable characteristics of ORN make both management and resolution of the disease process challenging, with 25% of cases recurring despite aggressive treatment with resection and reconstruction of the necrotic bone. In this article, we present a case of a 66-year-old man with unevoked ORN of the left posterior lingual mandibular cortex that was successfully treated and resolved with 6 months of pentoxifylline 400 mg twice a day and tocopherol 1000 IU every day. PMID- 22668441 TI - Proceedings of the dengue symposium at the 9th international congress of tropical pediatrics. PMID- 22668442 TI - Controversies in dengue pathogenesis. AB - Research into the pathogenesis of dengue fever has exploded over the last half century, with issues that were considered simple becoming more complex as additional data are found. This has led to the development of a number of controversies that are being studied across the globe and debated in the literature. In this paper, the following six controversies are analysed and, where possible, resolved: the 1997 World Health Organization (WHO) case definition of dengue haemorrhagic fever (DHF) is not useful; DHF is not significantly associated with secondary dengue infection; DHF results from infection with a 'virulent' dengue virus; DHF is owing to abnormal T-cell responses; DHF results from auto-immune responses; and DHF results from direct infection of endothelial cells. PMID- 22668443 TI - Community participation in the prevention and control of dengue: the patio limpio strategy in Mexico. AB - Community participation is vital to prevent and control the spread of dengue in Latin America. Initiatives such as the integrated management strategy for dengue prevention and control (IMS-Dengue) and integrated vector management (IVM) incorporate social mobilisation and behavioural change at the community level as part of a wider strategy to control dengue. These strategies aim to improve the efficacy, cost-effectiveness, environmental impact and sustainability of vector control strategies. Community empowerment is a key aspect of the strategy as it allows the local population to drive eradication of the disease in their environment. Through the patio limpio campaign, the concept of community participation has been employed in Mexico to raise awareness of the consequences of dengue. patio limpio consists of training local people to identify, eliminate, monitor and evaluate vector breeding sites systematically in households under their supervision. A community participation programme in Guerrero State found that approximately 54% were clean and free of breeding sites. Households that were not visited and assessed had a 2.4-times higher risk of developing dengue than those that were. However, after a year, only 30% of trained households had a clean backyard. This emphasises the need for a sustainable process to encourage individuals to maintain efforts in keeping their environment free of dengue. PMID- 22668444 TI - Dengue: an escalating public health problem in Latin America. AB - Dengue infection is a significant and escalating public health problem in Latin America. Its re-emergence and subsequent rise in the region over the past 50 years has largely been caused by a combination of a lack of political will, the radical growth of urban populations, migration flow and insufficient financial resources. Its increased incidence has been compounded by climate change, poor sanitation and extreme poverty, which lead to more breeding sites of the mosquito vector Aedes aegypti. In order to control dengue effectively, an integrated approach incorporating vector management and environmental and social solutions is required. To achieve success, these programmes require commitment and responses at both national and community level. The development of a vaccine is a vital tool in the fight against dengue. For successful introduction, those implementing vaccination need to be educated on the value of such a strategy. Effective political leadership, innovative financial mechanisms and co-operation across all disciplines, sectors and national borders are essential to eradication of the disease. PMID- 22668445 TI - The dengue situation in Africa. AB - Dengue outbreaks and epidemics have been reported in all regions of Africa, and it is believed that all four dengue virus serotypes are in circulation. Available data suggest that dengue is endemic to 34 African countries and that Aedes aegypti mosquitoes--the primary vector for dengue transmission--are known to be present in all but five countries. Whether populations in Africa are susceptible to dengue at the same rates as in Asia and Latin America is difficult to determine from the available data. Several factors may affect the transmission of dengue in Africa, including vector efficiency, viral infectivity, host vulnerability and environmental factors, such as increasing urbanisation. Current dengue prevention strategies in Africa focus on vector control, although the primary aim of such efforts is typically the prevention of malaria. Further research is needed to characterise the epidemiology of dengue in Africa and to better understand the factors involved in differences in vulnerability to dengue across Africa. PMID- 22668446 TI - Dengue fever and dengue haemorrhagic fever in adolescents and adults. AB - Dengue fever (DF) is endemic in tropical and subtropical zones and the prevalence is increasing across South-east Asia, Africa, the Western Pacific and the Americas. In recent years, the spread of unplanned urbanisation, with associated substandard housing, overcrowding and deterioration in water, sewage and waste management systems, has created ideal conditions for increased transmission of the dengue virus in tropical urban centres. While dengue infection has traditionally been considered a paediatric disease, the age distribution of dengue has been rising and more cases have been observed in adolescents and adults. Furthermore, the development of tourism in the tropics has led to an increase in the number of tourists who become infected, most of whom are adults. Symptoms and risk factors for dengue haemorrhagic fever (DHF) and severe dengue differ between children and adults, with co-morbidities and incidence in more elderly patients associated with greater risk of mortality. Treatment options for DF and DHF in adults, as for children, centre round fluid replacement (either orally or intravenously, depending on severity) and antipyretics. Further data are needed on the optimal treatment of adult patients. PMID- 22668447 TI - Dengue infections in travellers. AB - Dengue has been designated a major international public health problem by the World Health Organization (WHO). It is endemic in most tropical and sub-tropical countries, which are also popular tourist destinations. Travellers are not only at significant risk of acquiring dengue but they also contribute to its spread to non-endemic regions. Furthermore, they may serve as sentinels to alert the international community to epidemics in dengue-endemic regions. GeoSentinel, a global surveillance network, monitors all travel-related illnesses and estimates that dengue accounts for 2% of all illness in travellers returning from dengue endemic regions. In fact, in travellers returning from South-east Asia, dengue is now a more frequent cause of febrile illness than malaria. Dengue-infected travellers returning home to countries where the vector exists can place the local population at risk of further spread of the disease with subsequent autochthonous cycles of infection. The true incidence of dengue amongst travellers may be underestimated because of variability in reporting requirements in different countries and under-diagnosis owing to the non-specific clinical presentation of the disease. Risk factors for acquiring dengue include duration of stay, season of travel and epidemic activity at the destination. Any pre travel advice on the risks of developing dengue infections should consider these factors. PMID- 22668448 TI - The revised WHO dengue case classification: does the system need to be modified? AB - There has been considerable debate regarding the value of both the 1997 and 2009 World Health Organization (WHO) dengue case classification criteria for its diagnosis and management. Differentiation between classic dengue fever (DF) and dengue haemorrhagic fever (DHF) or severe dengue is a key aspect of dengue case classification. The geographic expansion of dengue and its increased incidence in older age groups have contributed to the limited applicability of the 1997 case definitions. Clinical experience of dengue suggests that the illness presents as a spectrum of disease instead of distinct phases. However, despite the rigid grouping of dengue into DF, DHF and dengue shock syndrome (DSS), overlap between the different manifestations has often been observed, which has affected clinical management and triage of patients. The findings of the DENCO study evaluating the 1997 case definitions formed the basis of the revised 2009 WHO case definitions, which classified the illness into dengue with and without warning signs and severe dengue. Although the revised scheme is more sensitive to the diagnosis of severe dengue, and beneficial to triage and case management, there remain issues with its applicability. It is considered by many to be too broad, requiring more specific definition of warning signs. Quantitative research into the predictive value of these warning signs on patient outcomes and the cost effectiveness of the new classification system is required to ascertain whether the new classification system requires further modification, or whether elements of both classification systems can be combined. PMID- 22668449 TI - Fluid management for dengue in children. AB - Dengue is a serious public health problem worldwide. Dengue shock syndrome (DSS), the severe form of dengue fever, can cause death within 12-24 hours if appropriate treatment is not promptly administered. For patients with DSS and the 30% of non-shocked dengue patients who require intravenous fluid therapy, a range of solutions is available for plasma volume support. Crystalloid solutions, such as normal 0.9% saline or Ringer's lactate, are the ones most commonly used. In severe cases, colloid solutions may be administered for their greater osmotic effect, although they carry a greater risk of adverse events. This paper summarises the key clinical data, comparing fluid regimens in children with severe dengue, and concludes that the majority of patients with DSS can be treated successfully with isotonic crystalloid solutions. If a colloid is thought necessary, a medium-molecular-weight preparation that combines good initial plasma volume support with good intravascular persistence and an acceptable side-effect profile is optimal. Further research should aim to determine whether there are benefits to early treatment with colloids, and which colloid solution is most effective for resuscitation of DSS patients. PMID- 22668450 TI - Attitudes towards smoking and tobacco control among pre-clinical medical students in Malaysia. AB - Physicians should play a leading role in combatting smoking; information on attitudes of future physicians towards tobacco control measures in a middle income developing country is limited. Of 310 future physicians surveyed in a medical school in Malaysia, 50% disagreed that it was a doctor's duty to advise smokers to stop smoking; 76.8% agreed that physicians should not smoke before advising others not to smoke; and 75% agreed to the ideas of restricting the sale of cigarettes to minors, making all public places smoke-free and banning advertising of tobacco-related merchandise. Future physicians had positive attitudes towards tobacco regulations but had not grasped their responsibilities in tobacco control measures. PMID- 22668451 TI - Synthesis and selective cytotoxic activity of novel hybrid chalcones against prostate cancer cells. AB - A new class of hybrid chalcones (17a-l &18a-l) was synthesized by Claisen-Schmidt condensation. All compounds were characterized by (1)H NMR, IR and mass spectral analysis and tested for their cytotoxic activity against PC-3 (prostate cancer), HT-29 (colon cancer), B-16 (mouse macrophages) and NCI-H460 (lung cancer) cell lines. Three compounds 18i, 18j and 18l (IC(50)=8.4, 7.9 & 5.9 MUM) showed significant activity against PC-3 cell line. PMID- 22668452 TI - Intrinsic metallic and semiconducting cubic boron nitride nanofilms. AB - We show by density functional theory calculations with both hybrid and semilocal functionals that cubic boron nitride (111) nanofilms are intrinsically metallic and even turn into semiconductors once the thickness is less than 0.69 nm, which is in sharp contrast to the known insulating nature of boron nitride materials. The exceptional metallic or semiconducting band gap is due to a combined effect of thickness-dependent inbuilt electric polarization and labile near-gap states unique in the polar nanofilms. The band gap and dipole moment of the nanofilms can be further significantly tuned by applying an in-plane strain. These distinguished features of the boron nitride nanofilms are robust to surface passivation and can be enhanced by hybridizing with diamond films, thereby opening an exciting prospect of using the versatile cubic nanofilms in future electronic and piezoelectric devices. PMID- 22668453 TI - Complementary and alternative medicine in dermatology: an overview of selected modalities for the practicing dermatologist. AB - According to survey data, 35-69% of patients with skin disease have used complementary and alternative medicine (CAM) in their lifetime. A literature search on this subject reveals a number of studies on the efficacy of CAM treatment for dermatologic conditions, as well as a number of articles showing the growing prevalence of CAM use amongst patients suffering from these conditions. Given the consensus amongst these articles that dermatologists require increased education on CAM, this paper presents an overview of some of the most widely used systems of alternative medicine to serve as a tool for practicing dermatologists. Specifically, the history and theory behind psychocutaneous therapies, traditional Chinese medicine (including acupuncture), homeopathy, and Ayurvedic medicine will be described, along with current evidence for their efficacy and reports of their adverse effects. The authors conclude that more evidence and better studies are needed for each of the major CAM modalities before they may be considered as independent therapeutic options. Moreover, given the shortage of evidence supporting the efficacy and safety of CAM, dermatologists should obtain a thorough history of CAM use from their patients. In general, ingestible substances including most homeopathic, Ayurvedic, and traditional Chinese medicine herbal formulations that are not US FDA regulated should be viewed with caution as they may cause severe adverse effects such as arsenicosis and hepatotoxicity. On the other hand, less invasive techniques such as acupuncture and psychocutaneous therapies may be more acceptable given their low-risk profile. Ultimately, until the availability of more sound data, these treatments should primarily be used in combination with conventional treatment and rarely independently. PMID- 22668455 TI - Dimerization mechanism of bis(triphenylphosphine)copper(I) tetrahydroborate: proton transfer via a dihydrogen bond. AB - The mechanism of transition-metal tetrahydroborate dimerization was established for the first time on the example of (Ph(3)P)(2)Cu(eta(2)-BH(4)) interaction with different proton donors [MeOH, CH(2)FCH(2)OH, CF(3)CH(2)OH, (CF(3))(2)CHOH, (CF(3))(3)CHOH, p-NO(2)C(6)H(4)OH, p-NO(2)C(6)H(4)N?NC(6)H(4)OH, p NO(2)C(6)H(4)NH(2)] using the combination of experimental (IR, 190-300 K) and quantum-chemical (DFT/M06) methods. The formation of dihydrogen-bonded complexes as the first reaction step was established experimentally. Their structural, electronic, energetic, and spectroscopic features were thoroughly analyzed by means of quantum-chemical calculations. Bifurcate complexes involving both bridging and terminal hydride hydrogen atoms become thermodynamically preferred for strong proton donors. Their formation was found to be a prerequisite for the subsequent proton transfer and dimerization to occur. Reaction kinetics was studied at variable temperature, showing that proton transfer is the rate determining step. This result is in agreement with the computed potential energy profile of (Ph(3)P)(2)Cu(eta(2)-BH(4)) dimerization, yielding [{(Ph(3)P)(2)Cu}(2)(MU,eta(4)-BH(4))](+). PMID- 22668454 TI - Use of community-level data in the National Children's Study to establish the representativeness of segment selection in the Queens Vanguard Site. AB - BACKGROUND: The WHO Multiple Exposures Multiple Effects (MEME) framework identifies community contextual variables as central to the study of childhood health. Here we identify multiple domains of neighborhood context, and key variables describing the dimensions of these domains, for use in the National Children's Study (NCS) site in Queens. We test whether the neighborhoods selected for NCS recruitment, are representative of the whole of Queens County, and whether there is sufficient variability across neighborhoods for meaningful studies of contextual variables. METHODS: Nine domains (demographic, socioeconomic, households, birth rated, transit, playground/greenspace, safety and social disorder, land use, and pollution sources) and 53 indicator measures of the domains were identified. Geographic information systems were used to create community-level indicators for US Census tracts containing the 18 study neighborhoods in Queens selected for recruitment, using US Census, New York City Vital Statistics, and other sources of community-level information. Mean and inter-quartile range values for each indicator were compared for Tracts in recruitment and non-recruitment neighborhoods in Queens. RESULTS: Across the nine domains, except in a very few instances, the NCS segment-containing tracts (N=43) were not statistically different from those 597 populated tracts in Queens not containing portions of NCS segments; variability in most indicators was comparable in tracts containing and not containing segments. CONCLUSIONS: In a diverse urban setting, the NCS segment selection process succeeded in identifying recruitment areas that are, as a whole, representative of Queens County, for a broad range of community-level variables. PMID- 22668458 TI - The importance of measurements. PMID- 22668456 TI - John wiley & sons. PMID- 22668460 TI - Author's response. PMID- 22668459 TI - Carbon taxes. PMID- 22668461 TI - Correction. PMID- 22668462 TI - HCFCs May Slow Ozone Layer Recovery. PMID- 22668463 TI - International. PMID- 22668464 TI - Federal. PMID- 22668465 TI - States. PMID- 22668466 TI - Technology. PMID- 22668467 TI - Awards. PMID- 22668468 TI - Science. PMID- 22668469 TI - Measurements. PMID- 22668470 TI - Business. PMID- 22668472 TI - Now get all the product. PMID- 22668471 TI - Clinton's Committee on the Environment and Natural Resources. PMID- 22668473 TI - Atmospheric Pressure Ionization LC/M. PMID- 22668474 TI - Deformities in birds of the great lakes region. PMID- 22668476 TI - METALS & AQUATI Contamination Workshop. PMID- 22668475 TI - The mercury cycle and fish in the adirondack lakes. PMID- 22668478 TI - Revising the particulate ambient air quality standard. PMID- 22668480 TI - Isotec inc. PMID- 22668479 TI - Performance-Based vs. Prescriptive Measurement Approaches. PMID- 22668482 TI - Marine natural products chemistry. PMID- 22668484 TI - Energy&Fuels(r). PMID- 22668485 TI - Air pollution. PMID- 22668487 TI - Biocides. PMID- 22668486 TI - Hazardous waste. PMID- 22668488 TI - Instruments. PMID- 22668489 TI - Water treatment. PMID- 22668490 TI - Standards. PMID- 22668491 TI - Publications. PMID- 22668492 TI - Software. PMID- 22668493 TI - Services. PMID- 22668494 TI - Stay ahead of the curve. PMID- 22668495 TI - Classified section. PMID- 22668496 TI - Atmospheric sciences. PMID- 22668497 TI - Air & waste management association. PMID- 22668499 TI - professional consulting services directory. PMID- 22668500 TI - Melanogenesis stimulation in B16-F10 melanoma cells induces cell cycle alterations, increased ROS levels and a differential expression of proteins as revealed by proteomic analysis. AB - Considering that stimulation of melanogenesis may lead to alterations of cellular responses, besides melanin production, our main goal was to study the cellular effects of melanogenesis stimulation of B16-F10 melanoma cells. Our results show increased levels of the reactive oxygen species after 15 h of melanogenesis stimulation. Following 48 h of melanogenesis stimulation, proliferation was inhibited (by induction of cell cycle arrest in the G1 phase) and the expression levels of p21 mRNA were increased. In addition, melanogenesis stimulation did not induce cellular senescence. Proteomic analysis demonstrated the involvement of proteins from other pathways besides those related to the cell cycle, including protein disulfide isomerase A3, heat-shock protein 70, and fructose biphosphate aldolase A (all up-regulated), and lactate dehydrogenase (down-regulated). In RT qPCR experiments, the levels of pyruvate kinase M2 mRNA dropped, whereas the levels of ATP synthase (beta-F1) mRNA increased. These data indicate that melanogenesis stimulation of B16-F10 cells leads to alterations in metabolism and cell cycle progression that may contribute to an induction of cell quiescence, which may provide a mechanism of resistance against cellular injury promoted by melanin synthesis. PMID- 22668501 TI - Stereoprogrammed direct synthesis of calixarene-based [3]rotaxanes. AB - Directional calixarene wheels were threaded along a bis(benzylalkylammonium) axle in a stereoprogrammed way to obtain the first examples of calixarene-based [3]rotaxanes. The base/acid treatment demonstrated that these systems act as nanosized molecular shuttles. An unprecedented switching between the tail-to-tail and head-to-head relative orientation of the calix-wheels was observed. PMID- 22668502 TI - Pharmacokinetics, tissue distribution and metabolism of senkyunolide I, a major bioactive component in Ligusticum chuanxiong Hort. (Umbelliferae). AB - ETHNOPHARMACOLOGICAL RELEVANCE: Ligusticum chuanxiong Hort. (Umbelliferae) is widely prescribed for treatment of cardiovascular diseases in China for centuries. One of the major bioactive components in L. chuanxiong is senkyunolide I (SEI), which shows pharmacological activities in anti-migraine and anti oxidative damage. MATERIALS AND METHODS: The aim of this study was to investigate in vivo pharmacokinetics, tissue distribution and metabolism of SEI in rats. The concentrations of SEI in plasma and tissues were determined by a high performance liquid chromatography (HPLC) method, and the pharmacokinetic parameters were calculated using and non-compartmental analysis. The metabolites were identified using high performance liquid chromatography tandem mass (HPLC-ESI-MS/MS) method. RESULTS: After oral and intravenous administration, SEI was quickly eliminated from plasma and its oral bioavailability (BA) was about 37.25%, which was smaller than intraportal BA (81.17%), but similar to intraduodenal BA (36.91%), suggesting that gastric first-pass effect of SEI is negligible, and hepatic first pass effect was approximately 18.83%. After oral administration, SEI could penetrate blood brain barrier and extensively distribute in tested tissues, with the descending order of AUC being kidney, liver, lung, muscle, brain, heart, thymus, and spleen in rat. The parent compound and nine metabolites were found and identified in rat bile after oral administration of SEI (36 mg/kg). The metabolic mechanism of SEI in rat mainly involves methylation, glucuronidation and glutathione conjugation during the phase II biotransformation pathway in rats. CONCLUSIONS: The information gained here may provide a meaningful basis for clinical application of such a bioactive compound of herbal medicines. PMID- 22668503 TI - Ethnomedicinal plants used to treat bone fracture from North-Central Western Ghats of India. AB - ETHNOPHARMACOLOGICAL RELEVANCE: North Central Western Ghats in India comprises rich bio-cultural diversity and is also home to varied ethnomedicinal practices. The study was taken up for documentation and analysis of traditional knowledge regarding the practice and use of plants in the treatment of bone fracture. This is an effort to preserve the vanishing wealth of traditional knowledge. MATERIALS AND METHODS: Key informants identified in a preliminary survey and collection of information was through semi structured, open ended interviews. The details on age, place of practice, experience of key informants and learning of practice, disease they treat and mode of diagnosis, storage and usage of plants were collected. The identity of plants and their information was confirmed through repeated guided transect walks in different seasons with the informants and focus group discussions. Identified plants were deposited at the herbaria of Regional Medical Research Centre, Belgaum. RESULTS: Forty four key informants providing treatment for bone fracture in this region were identified. Thirty eight plant species belonging to 24 families have been documented in the present study. Highest number of species representation is found in families Euphorbiaceae and Fabaceae. The habit of the species showed that 45% of the herbal drugs were obtained from trees, followed by herbs, shrubs and climbers and majority of plants used were collected from wild (76%). The stem or stem bark (33%) was most commonly used plant part to prepare medicine. Twenty six formulations of 30 plant species were directly used in treating bone fracture, where Cissus quadrangularis has the highest use-value (0.14). Eleven plants were found to be administered for bone strengthening, pain relieving, inflammation reduction and speedy recovery and Gmelina arborea has the highest use value (0.27). CONCLUSIONS: The results indicated the importance of traditional herbal practices in community for their health needs. Both conservational strategies and further validation studies are the need of the hour for better utilization and sustenance of the documented knowledge. PMID- 22668505 TI - Bivalirudin versus unfractionated heparin in percutaneous coronary interventions of patients having received initial fondaparinux treatment: a propensity matched study. AB - AIMS: Fondaparinux is an indirect, Factor Xa inhibitor that requires co administration of another anticoagulant with anti-Factor IIa activity for percutaneous coronary intervention (PCI) per guideline recommendations. In this setting, the use of bivalirudin, a direct Factor IIa inhibitor, is not well established. METHODS AND RESULTS: Using the Premier hospital database, we identified 971 patients who underwent elective or urgent PCI after receiving fondaparinux as the initial anticoagulant. They were treated with either bivalirudin +/- glycoprotein IIb/IIIa inhibitor (GPI) (Group A=618) or unfractionated heparin (UFH) +/- GPI (Group B=353) during PCI. A 2:1 propensity score matching (PSM) process was performed to control for patient and hospital level characteristics. The primary endpoints were to determine in-hospital death, bleeding and post-PCI length of stay (LOS) between treatment groups. After PSM, 512 matched patients were analysed (Group A=348 and Group B=174). In-hospital death was 1.4% in Group A vs. 2.9% in Group B (p=0.26). Clinically apparent bleeding occurred in 4.0% of Group A vs. 9.2% of Group B patients (p<0.02). Clinically apparent bleeding requiring transfusion was lower in Group A patients (0.6% vs. 2.9%; p=0.04). Post-PCI LOS was 1.9 +/- 3.8 days for Group A and 2.4 +/ 5.8 days for Group B (p=0.36). GPI use during PCI occurred in 9.2% of Group A vs. 44.8% of Group B patients (p<0.0001). CONCLUSIONS: After initial administration of fondaparinux, a bivalirudin-based strategy for PCI is associated with significantly reduced bleeding, with similar mortality and post PCI LOS when compared with an UFH-based strategy. PMID- 22668504 TI - Anti-inflammatory and anti-osteoarthritis effects of fermented Achyranthes japonica Nakai. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Achyranthyes japonica Nakai (AJN) has been traditionally used to control pain and improve dysfunction in osteoarthritis (OA) patients. AIM OF THE STUDY: The objectives of the present study were to investigate anti-inflammatory and anti-osteoarthritis activities of fermented AJN (FAJN). MATERIALS AND METHODS: Anti-inflammatory activity of non-fermented AJN (NFAJN) and FAJN was evaluated by in vitro assay using LPS-induced RAW 264.7 cells. In addition, their cartilage protective effects were also determined in vitro assay using SW1353 cell and in vivo model system using collagenase-induced arthritis (CIA) in rabbits. Moreover, we isolated and identified 20 hydroxyecdysone (20-HES) as a marker component in FAJN. RESULT: FAJN showed stronger anti-inflammatory activity than NFAJN through inhibiting production of NO and PGE2 in LPS-induced RAW 264.7, and lowering levels of MMP-3 release in SW1353 cells treated with TNF-a. FAJN contained higher levels of 20-HES, as a marker component, than AJN. FAJN ameliorates the progress of OA by inhibiting local inflammation. It does this by regulating levels of TNF-a and IL-4, and protecting articular cartilage by preventing destruction of proteoglycan, collagens, and also preventing injury to chondrocytes. CONCLUSION: Therefore, FAJN is a potential therapeutic agent for reduction of cartilage damage that occurs in OA. PMID- 22668506 TI - The single-giant unilamellar vesicle method reveals lysenin-induced pore formation in lipid membranes containing sphingomyelin. AB - Lysenin is a sphingomyelin (SM)-binding pore-forming toxin. To reveal the interaction of lysenin with lipid membranes, we investigated lysenin-induced membrane permeation of a fluorescent probe, calcein, through dioleoylphosphatidylcholine(DOPC)/SM, DOPC/SM/cholesterol(chol), and SM/chol membranes, using the single-giant unilamellar vesicle (GUV) method. The results clearly show that lysenin formed pores in all the membranes, through which membrane permeation of calcein occurred without disruption of GUVs. The membrane permeation began stochastically, and the membrane permeability coefficient increased over time to reach a maximum, steady value, Ps, which persisted for a long time(100--500 s), indicating that the pore concentration increases over time and finally reaches its steady value, NP s . The Ps values increased as the SM/lysenin ratio decreased, and at low concentrations of lysenin, the Ps values of SM/DOPC/chol (42/30/28)GUVs were much larger than those of SM/DOPC (58/42) GUVs. The dependence of Ps on the SM/lysenin ratio for these membranes was almost the same as that of the fraction of sodium dodecyl sulfate (SDS)-resistant lysenin oligomers, indicating that NP s increases as the SDS-resistant oligomer fraction increases. On the other hand, lysenin formed pores in GUVs of SM/chol(60/40) membrane, which is in a homogeneous liquid-ordered phase, indicating that the phase boundary is not necessary for pore formation. The Ps values of SM/chol (60/40) GUVs were smaller than those of SM/DOPC/chol (42/30/28) GUVs even though the SDS-resistant oligomer fractions were similar for both membranes, suggesting that not all of the oligomers can convert into a pore. On the basis of these results, we discuss the elementary processes of lysenin induced pore formation. PMID- 22668507 TI - Spectroelectrochemistry of a photochromic [2.2]paracyclophane-bridged imidazole dimer: clarification of the electrochemical behavior of HABI. AB - The photochromic behavior of the imidazole dimers can be attributable to the photoinduced homolytic cleavage of the C-N bond between the two imidazole rings. On the other hand, although the simultaneous formation of the imidazolyl radical and imidazole anion by the one-electron reduction of an imidazole dimer was reported, no definitive evidence for this electrochemical reaction has been demonstrated. We report the first direct evidence for the electrochemical generation of the imidazolyl radical from the radical anion of the imidazole dimer by conducting the UV-vis-NIR spectroelectrochemical analysis of the [2.2]paracyclophane-bridged imidazole dimer. PMID- 22668508 TI - REST is up-regulated by epidermal growth factor in HeLa cells and inhibits apoptosis by influencing histone H3 acetylation. AB - REST (repressor element 1-silencing transcription factor) is a transcription factor that recruits histone deacetylases to silence gene transcription. REST appears to play a paradoxical role in cancer cells: it exhibits tumor suppressor activity or promotes tumorigenesis, depending upon the setting. The extracellular signaling molecules that control REST gene expression in cancer cells remain poorly understood. In this study, we report that REST expression in HeLa cells is elevated in cells exposed to epidermal growth factor or serum, whereas the rate of cell apoptosis is low. Apoptosis induced by serum withdrawal is significantly increased in HeLa cells treated with an antisense phosphorothioate oligodeoxynucleotide (AS ODN) capable of down-regulating REST expression, whereas in HeLa cells transfected with a REST expressing plasmid, REST overexpression reduces the marked apoptosis caused, in absence of serum, by exposure to an anti Fas receptor antibody imitating the Fas ligand activity plus PD 98059, a blocker of extracellular signal-regulated kinase 1/2 activation. REST knockdown also reduces mRNA levels of the antiapoptotic protein Bcl-X(L) whereas in HeLa cells overexpressing REST, the reduction of Bcl-X(L) mRNA caused by the anti-Fas receptor antibody plus PD 98059 is significantly decreased. Finally, we report that acetylation of histone H3 is increased in HeLa cells exposed to AS ODN or anti-Fas receptor antibody, whereas it is reduced in cells transfected with the REST expressing plasmid. Our findings indicate that REST is a novel gene regulated by EGF in HeLa cells that potentially contributes to the modulation of apoptosis via epigenetic mechanisms. PMID- 22668510 TI - Occurrence and detection of phosphopeptide isomers in large-scale phosphoproteomics experiments. AB - The past decade has been marked by the emergence of selective affinity media and sensitive mass spectrometry instrumentation that facilitated large-scale phosphoproteome analyses and expanded the repertoire of protein phosphorylation. Despite these remarkable advances, the precise location of the phosphorylation site still represents a sizable challenge in view of the labile nature of the phosphoester bond and the presence of neighboring phosphorylatable residues within the same peptide. This difficulty is exacerbated by the combinatorial distribution of phosphorylated residues giving rise to different phosphopeptide isomers. These peptides have similar physicochemical properties, and their separation by LC is often problematic. Few studies have described the frequency and distribution of phosphoisomers in large-scale phosphoproteomics experiments, and no convenient informatics tools currently exist to facilitate their detection. To address this analytical challenge, we developed two algorithms to detect separated and co-eluting phosphopeptide isomers and target their subsequent identification using an inclusion list in LC-MS/MS experiments. Using these algorithms, we determined that the proportion of isomers present in phosphoproteomics studies from mouse, rat, and fly cell extracts represents 3-6% of all identified phosphopeptides. While conventional analysis can identify chromatographically separated phosphopeptides, targeted LC-MS/MS analyses using inclusion lists provided complementary identification and expanded the number of phosphopeptide isomers by at least 52%. Interestingly, these analyses revealed that the occurrence of phosphopeptides isomers can also correlate with the presence of extended phosphorylatable amino acids that can act as a "phosphorylation switch" to bind complementary domains such as those present in SR proteins and ribonucleoprotein complexes. PMID- 22668509 TI - Thymidine phosphorylase inhibits vascular smooth muscle cell proliferation via upregulation of STAT3. AB - Dysregulated growth and motility of vascular smooth muscle cells (VSMC) play important role in obstructive vascular diseases. We previously reported that gene transfer of thymidine phosphorylase (TP) into rat VSMC inhibits cell proliferation and attenuates balloon injury induced neointimal hyperplasia; however, the mechanism remains unclear. The current study identified a signaling pathway that mediates effect of TP inhibited VSMC proliferation with a TP activity-dependent manner. Rat VSMC overexpressing human TP gene (C2) or control empty vector (PC) were used. Serum stimulation induced constitutive STAT3 phosphorylation at tyrosine705 in C2 cell but not in PC, which was independent of JAK2 signaling pathway. Inhibition of Src family kinases activity inhibited STAT3 phosphorylation in C2 cells. Lyn activity was higher in C2 cell than in PC. SiRNA based gene knockdown of Lyn significantly decreased serum induced STAT3 phosphorylation in C2 and dramatically increased proliferation of this cell, suggesting that Lyn plays a pivotal role in TP inhibited VSMC proliferation. Unphosphorylated STAT3 (U-STAT3) expression was significantly increased in C2 cells, which may be due to the increased STAT3 transcription. Gene transfection of mouse wild-type or Y705F mutant STAT3 into PC cell or mouse primary cultured VSMC significantly reduced proliferation of these cells, suggesting that overexpression of U-STAT3 inhibits VSMC proliferation. We conclude that Lyn mediates TP induced STAT3 activation, which subsequently contributes to upregulate expression of U-STAT3. The U-STAT3 plays a critical role in inhibiting VSMC proliferation. PMID- 22668512 TI - A chemical cross-linking method for the analysis of binding partners of heat shock protein-90 in intact cells. AB - Members of the heat shock protein-90 (Hsp90) family are key regulators of biological processes through dynamic interaction with a multitude of protein partners. However, the transient nature of these interactions hinders the identification of Hsp90 interactors. Here we show that chemical cross-linking with ethylene glycolbis (succinimidylsuccinate), but not shorter cross-linkers, generated an abundant 240-kDa heteroconjugate of the molecular chaperone Hsp90 in different cell types. The combined use of pharmacological and genetic approaches allowed the characterization of the subunit composition and subcellular compartmentalization of the multimeric protein complex, termed p240. The in situ formation of p240 did not require the N-terminal domain or the ATPase activity of Hsp90. Utilizing subcellular fractionation techniques and a cell-impermeant cross linker, subpopulations of p240 were found to be present in both the plasma membrane and the mitochondria. The Hsp90-interacting proteins, including Hsp70, p60Hop and the scaffolding protein filamin A, had no role in governing the formation of p240. Therefore, chemical cross-linking combined with proteomic methods has the potential to unravel the protein components of this p240 complex and, more importantly, may provide an approach to expand the range of tools available to the study of the Hsp90 interactome. PMID- 22668517 TI - Improved methodology for the affinity isolation of human protein complexes expressed at near endogenous levels. AB - An efficient and reliable procedure for the capture of affinity-tagged proteins and associated complexes from human cell lines is reported. Through multiple optimizations, high yield and low background affinity-purifications are achieved from modest quantities of human cells expressing endogenous-level tagged proteins. Isolations of triple-FLAG and GFP-tagged fusion proteins involved in RNA metabolism are presented. PMID- 22668522 TI - Are all patients diagnosed with tuberculosis in Indian medical colleges referred to the RNTCP? AB - To assess the proportion of tuberculosis (TB) patients diagnosed in three medical colleges in the states of West Bengal and Meghalaya who benefited from the services provided under the Revised National Tuberculosis Control Programme (RNTCP), a line list of patients with reports of investigations suggesting probable or confirmed TB was prepared from the records of the pathology, radiology and microbiology departments. This was compared with another line list prepared using RNTCP records. Only 150 (36%) of 420 probable or confirmed TB patients were referred to the RNTCP services. This suggests a need for more intensive supervision and training of medical college faculty. PMID- 22668523 TI - Combined theoretical and computational study of interstrand DNA guanine-guanine cross-linking by trans-[Pt(pyridine)2] derived from the photoactivated prodrug trans,trans,trans-[Pt(N3)2(OH)2(pyridine)2]. AB - Molecular modeling and extensive experimental studies are used to study DNA distortions induced by binding platinum(II)-containing fragments derived from cisplatin and a new class of photoactive platinum anticancer drugs. The major photoproduct of the novel platinum(IV) prodrug trans,trans,trans [Pt(N(3))(2)(OH)(2)(py)(2)] (1) contains the trans-{Pt(py)(2)}(2+) moiety. Using a tailored DNA sequence, experimental studies establish the possibility of interstrand binding of trans-{Pt(py)(2)}(2+) (P) to guanine N7 positions on each DNA strand. Ligand field molecular mechanics (LFMM) parameters for Pt-guanine interactions are then derived and validated against a range of experimental structures from the Cambridge Structural Database, published quantum mechanics (QM)/molecular mechanics (MM) structures of model Pt-DNA systems and additional density-functional theory (DFT) studies. Ligand field molecular dynamics (LFMD) simulation protocols are developed and validated using experimentally characterized bifunctional DNA adducts involving both an intra- and an interstrand cross-link of cisplatin. We then turn to the interaction of P with the DNA duplex dodecamer, d(5' C(1)C(2)T(3)C(4)T(5)C(6)G(7)T(8)C(9)T(10)C(11)C(12)-3').d(5' G(13)G(14)A(15)G(16)A(17)C(18)G(19)A(20)G(21)A(22)G(23)G(24)-3') which is known to form a monofunctional adduct with cis-{Pt(NH(3))(2)(py)}. P coordinated to G(7) and G(19) is simulated giving a predicted bend toward the minor groove. This is widened at one end of the platinated site and deepened at the opposite end, while the P-DNA complex exhibits a global bend of ~67 degrees and an unwinding of ~20 degrees . Such cross-links offer possibilities for specific protein-DNA interactions and suggest possible mechanisms to explain the high potency of this photoactivated complex. PMID- 22668524 TI - Agomelatine treatment with adolescents with ADHD. AB - OBJECTIVE: Antidepressants, in particular Atomextine, along with stimulants have demonstrated benefit in the treatment of ADHD. Agomelatine is a new antidepressant with additional affinities to the melatonergic system. As ADHD has been associated with sleep disorders, it is assumed that Agomelatiine might serve as a therapeutic alternative to treat patients with the ADHD refractory to first line medications. METHOD: Ten late adolescents were evaluated in a placebo controlled manner. RESULTS: Agomelatine's effect was superior to that of placebo but appeared to be less than that of first line medications such as methylphenidate. CONCLUSION: Agomelatine may be a useful second line medication for individuals with ADHD, particularly if they suffer from additional sleep disorders. PMID- 22668525 TI - Revisiting emergency anti-apoptotic cytokinotherapy: erythropoietin synergizes with stem cell factor, FLT-3 ligand, trombopoietin and interleukin-3 to rescue lethally-irradiated mice. AB - We have re-evaluated the benefit of using erythropoietin (Epo) as a pleiotropic cytokine to counteract hematological and extra-hematological toxicity following lethal irradiation. B6D2F1 mice were exposed to a dose of 9 Gy gamma radiation resulting in 90% mortality at 30 days, and then injected with stem cell factor, FLT-3 ligand, thrombopoietin and interleukin-3 [i.e. SFT3] at two and 24 hours with or without Epo (1,000 IU/kg) at 2 hours and day 8. As controls, two groups of irradiated mice were given only Epo or Phosphate-buffered saline. Epo synergized with SFT3 to rescue lethally-irradiated mice from radiation-induced death (survival: 60%, 95% and 5% respectively for SFT3, SFT3+Epo and controls at 30 days, p<0.05), whereas Epo alone exhibited no protective effect. Hematopoietic parameters did not differ significantly between SFT3 and SFT3+Epo groups during the animal death period. Some beneficial effects on gastro-intestinal toxicity were noticed following administration of Epo, although lung, liver and kidney were not protected. Further studies are necessary to understand fully the mechanisms involved in these effects of Epo in order to optimize treatment with cytokines following high-dose irradiation. PMID- 22668526 TI - Factors affecting the prognosis of Albanian adult patients with generalized tetanus. AB - BACKGROUND: Despite systematic vaccination of the population, tetanus continues to be a health problem in Albania, as in some other developing countries. In this study, our intent was to evaluate prognostic factors relating to death in adult patients with generalized tetanus. METHODOLOGY AND PATIENTS: All the patients (60) included in the study were hospitalized at the regional hospitals of Shkodra and Korca, and the University Hospital Centre "Mother Theresa" of Tirana, Albania, during the period of 1984-2004. They had a mean age of 49.1+14.4 years, 43 (71.7%) were males and 40 (66.6%) of them lived in rural areas. The mean incubation period was 12 days and the case-fatality rate (CFR) was 38.3%. RESULTS: The CFR in patients with an onset period >=2 days was 21.7% and in those with <2 days was 48.6%, OR=0.29 (p<0.05). Patients >50 years old had a CFR=60.87% (OR=7, p<0.05). We found the high CFR to be significantly associated with urban residency, male gender, complicated wound, head localization, fever >= 38.4 degrees C, tachycardia > 120 beats/min, and hypertension. DISCUSSION: The main prognostic factor of those analyzed in our study appeared to be the onset period and the age of the patients. We didn't find significant differences in CFR in patients with different incubation periods. Clinicians must take into account that wound complication and localization, tachycardia and hypertension, high fever, male gender and urban residency significantly influence the prognoses of adults with generalized tetanus. PMID- 22668527 TI - Ulnar artery aneurysm: case report and review of the literature. AB - AIM: We report a case of ulnar and palmar arch artery aneurysm in a 77 years old man without history of any occupational or recreational trauma, vasculitis, infections or congenital anatomic abnormalities. We also performed a computed search of literature in PUBMED using the keywords "ulnar artery aneurysm" and "palmar arch aneurysm". CASE REPORT: A 77 years old male patient was admitted to hospital with a pulsing mass at distal right ulnar artery and deep palmar arch; at ultrasound and CT examination a saccular aneurysm of 35 millimeters at right ulnar artery and a 15 millimeters dilatation at deep palmar arch were detected. He was asymptomatic for distal embolization and pain. In local anesthesia ulnar artery and deep palmar arch dilatations were resected. Reconstruction of vessels was performed through an end-to-end microvascular repair. Histological examination confirmed the absence of vasculitis and collagenopaties. In postoperative period there were no clinical signs of peripheral ischemia, Allen's test and ultrasound examination were normal. At follow-up of six months, the patient was still asymptomatic with a normal Allen test, no signs of distal digital ischemia and patency of treated vessel with normal flow at duplex ultrasound. CONCLUSION: True spontaneous aneurysms of ulnar artery and palmar arch are rare and can be successfully treated with resection and microvascular reconstruction. PMID- 22668528 TI - Modified patch repair of femoral hernia after inguinal herniorrhaphy. AB - BACKGROUND AND AIM: It has been reported that femoral hernias are rather common after a previous repair of inguinal hernia. We herein present a modified patch repair technique for large femoral hernias that develop after a Lichtenstein operation for ipsilateral inguinal hernia. PATIENTS AND METHODS: The modified technique for femoral hernia was applied to three patients who had a Lichtenstein repair for inguinal hernia. All patients were male. Hernia sac is dissected completely and sent back into to the preperitoneal space. Special attention should be given to the prevascular component of the sac. It is dissected as deep as possible into the preperitoneal space over the femoral vein. The defect is quite wide in this particular type of femoral hernia following Lichtenstein repair. A prosthetic patch that matches the defect is prepared. The medial edge of the mesh is configured to correspond to the pubic corner and lacunar ligament. The lateral margin of the patch is cut to create several petals for inverting the mesh above and medial to the femoral vein to prevent prevascular herniation. The mesh is secured to inguinal ligament, ilioinguinal tract, lacunar ligament, and Cooper ligament. Few sutures are put on the pubic corner and lacunar ligament. RESULTS: One patient was discharged after two hours, other two stayed overnight. Readmission because of seroma development was recorded in two cases where standard polypropylene meshes were used. No complication was observed in the other patient who received lightweight meshes. No early recurrences were recorded after 4, 9, and 30 months. CONCLUSION: Femoral recurrence after previous inguinal hernia repair seems to be a specific entity. It has a prevascular component and the hernia defect can be much larger than that of a primary femoral hernia. A patch repair with infra-inguinal approach can be a valuable alternative with low complication rate. PMID- 22668529 TI - Delayed and occult splenic rupture: a diagnostic puzzle. AB - Splenic rupture is a common complaint encountered in emergency surgery. Trauma is the most common cause of splenic rupture, while non-traumatic or occult splenic rupture (OSR) is a rare condition. The differential diagnosis weighs on treatment that ranges between close monitoring, splenorrhaphy, splenic conservation and splenectomy. We report a case of an 63-year-old man presenting with acute atraumatic left upper quadrant pain. Preliminary diagnosis was subsequently determined to be a hematoma secondary to OSR. More accurate detailed history revealed a previous trauma, which occurred more than one year before and mimicked an OSR. Delayed and occult splenic rupture are as different diagnosis as different treatment. Even in emergency surgery, the key for a target therapeutic strategy should consider an accurate diagnostic time. PMID- 22668530 TI - Adenosquamous carcinoma of the esophagogastric junction. Case report. AB - Adenosquamous carcinoma is a rare tumor with coexisting elements of infiltrating squamous cell carcinoma and adenocarcinoma. This tumor is reported to arise in different organs but rarely in the oesophagus. In most cases, it shows highly aggressive biological behaviour with high propensity to regional lymph-node metastasis and poor prognosis. We describe the management of a patient with an aggressive adenosquamous carcinoma of the esophagogastric junction. PMID- 22668531 TI - Laparoscopic treatment of mucinous adenocarcinoma of jejunum associated with celiac disease. Case report. AB - Mucinous adenocarcinoma of the small bowel is very rare, and only few cases have been described in the literature. Association of this tumor with celiac disease has never been published. The authors report a unique case of jejunal mucinous adenocarcinoma in which a concomitant celiac disease has been histologically recognized. The difficult diagnosis, the role of laparoscopic surgery and the relationship between small bowel tumors and celiac disease are discussed. A 49 year-old man presented with recurrent melena, nausea, vomiting and anemia. A stenosis of the jejunum was documented by means of CT scan and video capsule enteroscopy. A laparoscopy was scheduled. A tumor, found in the first jejunal loop, was removed by laparoscopic surgery. Histopathology revealed a rare mucinous adenocarcinoma associated with epithelial changes secondary to celiac disease. Although small bowel tumors are rare entity, in patients with celiac disease complaining of symptoms related to altered intestinal transit or occult bleeding, an appropriate work-up should be planned for diagnosis. Mucinous type intestinal adenocarcinoma, even if never published before, could be observed. Laparoscopic surgery is often essential for the diagnosis and treatment. PMID- 22668532 TI - Cecal volvulus during pregnancy. Case report. AB - INTRODUCTION: Acute intestinal obstruction in pregnancy is a rare, but life threatening complication associated with high fetal and maternal mortality. CASE REPORT: A 20-year old gravida presented with a 24 hour history of several episodes of vomiting, complete constipation and severe crampy abdominal pain. The patient was admitted with the diagnosis of acute abdomen associated with septic shock. On examination echography showed distended intestinal loops and presence of free peritoneal fluid. Abdominal X-ray with shielding of the fetus revealed colonic air-fluid levels. The obstetrician consult diagnosed dead fetus in utero and was decided to operate immediately. On laparotomy was found complete cecal volvulus with gangrene of cecum, part of ascending colon and terminal ileum. A right hemicolectomy was performed with side to side ileotransverse anastomosis. Afterwards a lower segment cesarean section was made and a stillborn fetus was delivered. The patient made an uneventful recovery and was discharged on 9th postoperative day. CONCLUSION: Cecal volvulus during pregnancy is a rare, but serious surgical problem. Correct diagnosis may be difficult until exploratory laparotomy is performed. Undue delay in diagnosis and surgical treatment can increase the maternal and fetal mortality. PMID- 22668533 TI - Management and follow-up of a patient with Familial Atypical Multiple Mole Melanoma (FAMMM) Syndrome. AB - INTRODUCTION: Familial Atypical Multiple Mole-Melanoma Syndrome (FAMMM) is an autosomal dominant genodermatosis characterized by the presence of a high number of dysplastic nevi and family history of melanoma or pancreatic cancer. Melanomas in FAMMM patients tend to occur at a younger age, although they are clinically similar to sporadic melanomas in terms of overall survival. CASE REPORT: A 45 year-old woman with a family history of melanoma, a type II phototype and numerous (>100) nevi was admitted to our Department of Dermatology and Plastic Surgery. Over the past years, the patient underwent several surgical operations to remove pigmented lesions and two are dysplastic nevi. Since 1995, she underwent surgery to remove four melanomas. She is followed for skin examinations including dermoscopy. CONCLUSION: Identifying high-risk patients for melanoma represents a primary objective for the specialists that are involved in the management of this disease, especially in order to enact all the necessary surveillance and follow-up strategies. PMID- 22668534 TI - Multicentric osteolytic lesion of the middle finger of the hand. Case report. AB - Giant cell-rich osteolytic lesions may have overlapping clinical, radiologic, and histopathologic features, with an important degree of difficulty of diagnosis and treatment. We report a case of double osteolytic lesion at the middle-finger in a young man without previous history of hand trauma. He underwent en-bloc resection of the bone lesions and reconstruction by graft of hydroxyapatite, resulting in a good morpho-functional result. Histological diagnosis was giant cell reparative granuloma (GCRG), although several features were considered atypical, including the appearance of the giant cells and the areas of the stroma that more closely resembled a giant cell tumor. GCRG is a benign rare intraosseous lesion and the true nature is controversial and unknown. The theories are that it could be a reactive lesion, a developmental anomaly or a benign neoplasm. It appears as an osteolytic lesion that must be considered in the differential diagnosis of other "critical" bone lesions similar in clinical, as well as radiologic and pathological appearance. Further characterization studies are helpful and necessary for the proper management. PMID- 22668535 TI - What kind of surgery for cervical carcinoma? AB - The incidence and mortality of cervical cancer have changed over the past 50 years in developed countries, but this kind of tumor still remains a significant clinical problem because it is the second most common cause of morbidity and mortality from cancer among women. After histological confirmation of invasive cervical cancer, the extent of disease was determined using clinical criteria to assign a stage. This assessment is important because, while for the other gynecologic cancers clinical information obtained by surgery and histopathological examination is implemented and concurs to define the staging of the disease, the cervical cancer tumor stage is given after the primary diagnosis. In this review we discuss how the surgical approach to cervical cancer has been evolved, in order to modulate the radicality of the intervention itself and thus to preserve the pelvic innervation. This step has been achieved by deepening knowledge of functional pelvic anatomy and modulating the radicality of hysterectomy according to well defined surgical landmarks. PMID- 22668536 TI - Congenital optic disc anomalies. PMID- 22668537 TI - Pediatric optic atrophy. PMID- 22668538 TI - Pediatric optic neuritis. PMID- 22668539 TI - Pediatric pseudotumor cerebri. AB - Although PTC most frequently occurs in obese females of childbearing age, the syndrome occurs in children as well.(3),(5) Prepubertal children with PTC have a lower incidence of obesity compared with adults and there is no sex predilection. The onset of puberty is best defined by the onset of secondary sexual characteristics such has menarche, pubic hair, and breast development. Children with PTC have a higher incidence of associated conditions and cranial nerve deficits compared with adults. Similar to adult patients, children are at risk for the development of permanent visual loss. In rare instances, children initially diagnosed with PTC will be found to harbor an intracranial neoplasm such as gliomatosis cerebri. An intracranial pressure of 28 cm H2O has recently been established as the upper limit of normal in children.31 Treatment is indicated for the symptomatic management of headaches and to preserve vision. Most children respond to medications such as acetazolamide, furosemide, or topiramate. Surgical treatment such as ONSF and shunting procedures are indicated for children with severe headaches, visual loss, or both despite maximal tolerated medical treatment. PMID- 22668540 TI - Pediatric neurovascular disorders. PMID- 22668541 TI - Neuro-ophthalmic features of the neurocutaneous syndromes. AB - This review highlights the diagnostic criteria and neuro-ophthalmic symptoms and signs of the more commonly seen neurocutaneous disorders, including NF1 and NF2, tuberous sclerosis, VHL disease, Sturge-Weber disease, and AT. The distinct neuro ophthalmic features in each of these hereditary and congenital disorders play an important role in clinical diagnosis. PMID- 22668542 TI - Vigabatrin-associated visual field loss. PMID- 22668543 TI - Pediatric brain tumors: the neuro-ophthalmic impact. PMID- 22668544 TI - Nonorganic visual loss in children. AB - NOVL in children is a relatively common problem for the comprehensive ophthalmologist. Although the etiology and pathophysiology of NOVL are variable, rare cases are because of physical or sexual abuse. Clinical tests can make the diagnosis of NOVL, and nonorganic is our preferred terminology for NOVL. Clinicians should be careful to establish a normal eye examination and prove that the vision is better than claimed before labeling a patient with NOVL. Rarely, the clinical examination is insufficient to establish the diagnosis of NOVL and electrophysiology may be helpful. Reassurance is generally all that is necessary for most children with NOVL, but some patients might benefit from formal psychiatric evaluation. The possibility of nonorganic overlay should also be considered in children with NOVL, and the combination of organic and NOVL is relatively common. PMID- 22668547 TI - Intracranial aneurysms are much less common in children than in adults, and instead other vascular malformations such as arteriovenous malformations are more common. Preface. PMID- 22668548 TI - Treatment of atrophic diaphyseal humeral nonunions with compressive locked plating and augmented with an intramedullary strut allograft. AB - OBJECTIVE: The aim of this study was to evaluate the effectiveness of thorough debridement and locked compression plating augmented with an intramedullary fibular allograft for the treatment of atrophic diaphyseal humeral nonunions. DESIGN: The study involved a level 4 retrospective case series. SETTING: This study was conducted at a level 1 university trauma center. PATIENTS: Twenty patients with painful atrophic nonunions of the humeral diaphysis were examined. INTERVENTION: This involved a thorough debridement and locked compression plating augmented with an intramedullary fibular allograft. MAIN OUTCOME MEASURES: These were union rate, shoulder range of motion, visual analog scale (VAS) pain, VAS function, patient satisfaction, and American Shoulder and Elbow Surgeons score at latest follow-up. METHODS: Clinical and radiographic examinations were performed preoperatively and postoperatively. VAS pain and function scores were collected preoperatively and postoperatively. Patient satisfaction and ASES scores were recorded at the time of the most recent follow-up. RESULTS: : Bony union was achieved in 19 of 20 patients (95%). The patients demonstrated an average improvement in forward elevation from 65 to 144 degrees (P = 0.001), abduction from 48 to 133 degrees (P < 0.001), external rotation from 34 to 70 degrees (P = 0.05), and internal rotation from S1 to T12 (P = 0.025). VAS pain scores improved from 6.05 to 1.88 (P = 0.032). VAS function scores improved from 2.06 to 7.75 (P = 0.003). The average postoperative ASES score was 76, and the average patient satisfaction was rated 9.3/10. CONCLUSIONS: Atrophic nonunions of the humerus can be successfully treated with debridement of the nonunion, coupled with the use of a fibular allograft and locked compression plating. This technique leads to predictable healing without the morbidity associated with autograft. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence. PMID- 22668549 TI - Current world literature. PMID- 22668554 TI - Stent thrombosis with everolimus-eluting stents: meta-analysis of comparative randomized controlled trials. AB - BACKGROUND: Some but not all studies have reported reduced rates of stent thrombosis (ST) with everolimus-eluting stents (EES) compared with other drug eluting stents (DES). All of these studies were insufficiently powered to reliably detect differences in ST. We therefore performed a meta-analysis of randomized controlled trials comparing the risk of 2-year definite ST between EES and other DES. METHODS AND RESULTS: Randomized controlled trials comparing EES versus other DES were searched through MEDLINE, EMBASE, Cochrane databases, and proceedings of international meetings. Information on study design, inclusion and exclusion criteria, sample characteristics, and clinical outcomes was extracted. Eleven randomized controlled trials (16,775 patients) were analyzed, including 5 trials (n=7113) of EES versus paclitaxel-eluting stents, 5 trials (n=7370) of EES versus sirolimus-eluting stents, and 1 trial (n=2292) of EES versus zotarolimus eluting stents. By 2 years definite ST with EES compared with pooled DES occurred in 0.5% versus 1.3% patients, respectively (relative risk, 0.38; 95% CI, 0.24 0.59; P<0.0001). Similar results were observed when the broader definition of definite/probable ST was considered (relative risk, 0.46; 95% CI, 0.33-0.66; P<0.0001). EES compared with other DES reduced the relative risk of early ST (within 30 days), late ST (31 days to 1 year), cumulative 1-year ST, and very late ST (1-2 years). The reduced rate of definite ST observed with EES was consistent across all DES comparators with no interactions apparent during any time interval. CONCLUSIONS: EES compared with a pooled group of paclitaxel eluting stents, sirolimus-eluting stents, and zotarolimus-eluting stents is associated with a significant reduction of definite ST, an effect that appears early and increases in magnitude through at least 2 years. PMID- 22668555 TI - Prolonged clopidogrel use after bare metal and drug-eluting stent placement: the Veterans Administration drug-eluting stent study. AB - BACKGROUND: Current guidelines recommend combining clopidogrel with aspirin for up to 1 year after coronary stenting, but the value of clopidogrel beyond this time is uncertain. METHODS AND RESULTS: We evaluated all patients in the Veterans Administration healthcare system receiving either drug-eluting or bare metal stents from 2002 to 2006. The Veterans Administration National Patient Care and Pharmacy databases were used to extract patient characteristics, duration of clopidogrel use, and outcomes for up to 4 years after the index procedure. We used Cox proportional hazards to estimate hazard ratios for death, myocardial infarction, revascularization, and bleeding from a 12-month landmark after stenting that excluded patients with events within the first 12 months. Of 42,254 patients, 29,175 met the study inclusion criteria. Compared with <=12 months of clopidogrel, prolonged clopidogrel (>12 months) was associated with a lower adjusted risk of death for both drug-eluting stents (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.61, 0.82; P<0.01) and bare metal stents (HR, 0.85; 95% CI, 0.76, 0.96; P=0.01) as well as for death and myocardial infarction but was unrelated to stroke or major bleeding. The effect of prolonged clopidogrel on death or myocardial infarction was significantly greater among patients receiving drug-eluting (HR, 0.70; 95% CI, 0.64, 0.84) compared with bare metal stents (HR, 0.88; 95% CI, 0.79, 0.98; interaction P=0.024). CONCLUSIONS: Patients receiving clopidogrel beyond 12 months had a lower risk of death or myocardial infarction compared patients receiving clopidogrel <=12 months. The risk reduction was greater for drug-eluting stents. These data support longer durations of dual antiplatelet therapy for patients receiving a stent, particularly for those receiving a drug-eluting stent. PMID- 22668556 TI - Predictors and prognostic value of myocardial injury during transcatheter aortic valve implantation. AB - BACKGROUND: Myocardial injury is a common complication during cardiac surgery and percutaneous coronary intervention and is associated with postprocedural cardiovascular morbidity and mortality. Limited data have been reported about the occurrence of myocardial damage associated with transcatheter aortic valve implantation (TAVI). Therefore, our purpose was to investigate the incidence, predictors, and prognostic value of myocardial injury during TAVI. METHODS AND RESULTS: We studied 119 patients (aged 81+/-8 years; 47 male) who had undergone a TAVI with the Medtronic-CoreValve bioprosthesis. Serum creatine kinase-MB (CK-MB) and cardiac troponin T (cTnT) levels were measured before and after the procedure. Myocardial injury was defined as a postprocedural increase of CK-MB and/or cTnT level >5 times the upper reference limit. After TAVI, the incidence of myocardial injury was 17%, which was independently predicted by procedural duration (in minutes) (odds ratio [OR], 1.04; 95% CI, 1.01-1.06), preprocedural beta-blocker use (OR, 0.12; 95% CI, 0.03-0.45), peripheral arterial disease (OR, 6.36; 95% CI, 1.56-25.87), and prosthesis depth (in millimeters) (OR, 1.31; 95% CI, 1.08-1.59). The 30-day mortality after TAVI was 13% and was independently predicted by myocardial injury (OR, 8.54; 95% CI, 2.17-33.52), preprocedural hospitalization (OR, 9.36; 95% CI, 2.55-34.38), and left ventricular mass index (in g/m(2)) (OR, 1.02; 95% CI, 1.00-1.03). CONCLUSIONS: After transcatheter aortic valve implantation, serum levels of both CK-MB and cTnT increase, reflecting the occurrence of periprocedural myocardial injury. A longer procedural duration, the absence of beta-blocker use, peripheral arterial disease, and a deeper prosthesis insertion are associated with myocardial injury. Together with preprocedural hospitalization and left ventricular mass, myocardial injury is an independent predictor for 30-day mortality after TAVI. PMID- 22668557 TI - Effect of an MCM4 mutation that causes tumours in mouse on human MCM4/6/7 complex formation. AB - It has been reported that a point mutation of minichromosome maintenance (MCM)4 causes mammary carcinoma, and it deregulates DNA replication to produce abnormal chromosome structures. To understand the effect of this mutation at level of MCM2 7 interaction, we examined the effect of the same mutation of human MCM4 on the complex formation with MCM6 and MCM7 in insect cells. Human MCM4/6/7 complexes containing the mutated MCM4 were formed, but the hexameric complex formation was not evident in comparison with those containing wild-type MCM4. In binary expression of MCM4 and MCM6, decreased levels of MCM6 were recovered with the mutated MCM4, compared with wild-type MCM4. These results suggest that this mutation of MCM4 perturbs proper interaction with MCM6 to affect complex formation of MCM4/6/7 that is a core structure of MCM2-7 complex. Consistent with this notion, nuclear localization and MCM complex formation of forcedly expressed MCM4 in human cells are affected by this mutation. Thus, the defect of this mutant MCM4 in interacting with MCM6 may generate a decreased level of chromatin binding of MCM2-7 complex. PMID- 22668558 TI - Function analysis of conserved amino acid residues in a Mn(2+)-dependent protein phosphatase, Pph3, from Myxococcus xanthus. AB - The Myxococcus xanthus protein phosphatase Pph3 belongs to the Mg(2+)- or Mn(2+) dependent protein phosphatase (PPM) family. Bacterial PPMs contain three divalent metal ions and a flap subdomain. Putative metal- or phosphate-ion binding site specific mutations drastically reduced enzymatic activity. Pph3 contains a cyclic nucleotide monophosphate (cNMP)-binding domain in the C-terminal region, and it requires 2-mercaptoethanol for phosphatase activity; however, the C-terminal deletion mutant showed high activity in the absence of 2-mercaptoethanol. The phosphatase activity of the wild-type enzyme was higher in the presence of cAMP than in the absence of cAMP, whereas a triple mutant of the cNMP-binding domain showed slightly lower activities than those of wild-type, without addition of cAMP. In addition, mutational disruption of a disulphide bond in the wild-type enzyme increased the phosphatase activity in the absence of 2-mercaptoethanol, but not in the C-terminal deletion mutant. These results suggested that the presence of the C-terminal region may lead to the formation of the disulphide bond in the catalytic domain, and that disulphide bond cleavage of Pph3 by 2 mercaptoethanol may occur more easily with cAMP bound than with no cAMP bound. PMID- 22668559 TI - Mediator CDK subunits are platforms for interactions with various chromatin regulatory complexes. AB - The Mediator complex consists of more than 20 subunits. This is composed of four modules: head, middle, tail and CDK/Cyclin. Importantly, Mediator complex is known to play pivotal roles in transcriptional regulation, but its molecular mechanisms are still elusive. Many studies, including our own, have revealed that CDK8, a kinase subunit of the CDK/Cyclin module, is one of the key subunits involved in these roles. Additionally, we previously demonstrated that a novel CDK component, CDK19, played similar roles. It is assumed that various factors that directly affect transcriptional regulation target these two CDKs; thus, we conducted yeast two-hybrid screenings to isolate the CDK19-interacting proteins. From a screening of 40 million colonies, we obtained 287 clones that provided positive results encoded mRNAs, and it turned out that 59 clones of them encoded nuclear proteins. We checked the reading frames of the candidate clones and obtained three positive clones, all of which encoded the transcriptional cofactors, Brahma-related gene 1, B-cell CLL/lymphoma 6 and suppressor of zeste 12 homolog. Intriguingly, these three cofactors are also related to chromatin regulation. Further studies demonstrated that those could bind not only to CDK19 but also to CDK8. These results help elucidate the functional mechanism for the mutual regulations between transcription and chromatin. PMID- 22668560 TI - Integrated, home-based treatment for MDR-TB and HIV in rural South Africa: an alternate model of care. AB - SETTING: Treatment outcomes for multidrug-resistant tuberculosis (MDR-TB) in South Africa have suffered as centralized, in-patient treatment programs struggle to cope with rising prevalence and human immunodeficiency virus (HIV) co infection rates. A new treatment model is needed to expand treatment capacity and improve MDR-TB and HIV outcomes. OBJECTIVE: To describe the design and preliminary results of an integrated, home-based MDR-TB-HIV treatment program created in rural KwaZulu-Natal. METHOD: In 2008, a decentralized center was established to provide out-patient MDR-TB and HIV treatment. Nurses, community health workers and family supporters have been trained to administer injections, provide adherence support and monitor adverse reactions in patients' homes. Physicians assess clinical response, adherence and the severity of adverse reactions to MDR-TB and HIV treatment at monthly follow-up visits. Treatment outcomes are assessed by monthly cultures and CD4 and viral load every 6 months. RESULTS: Of 80 patients initiating MDR-TB treatment from February 2008 to April 2010, 66 were HIV-co-infected. Retention has been high (only 5% defaults, 93% of visits attended), and preliminary outcomes have been favorable (77% cured/still on treatment, 82% undetectable viral load). Few patients have required escalation of care (9%), had severe adverse events (8%) or died (6%). CONCLUSION: Integrated, home-based treatment for MDR-TB and HIV is a promising treatment model to expand capacity and achieve improved outcomes in rural, resource-poor and high HIV prevalent settings. PMID- 22668561 TI - Two novel de novo mutations of KRT6A and KRT16 genes in two Chinese pachyonychia congenita pedigrees with fissured tongue or diffuse plantar keratoderma. AB - BACKGROUND: Mutations in the KRT6A or KRT16 gene cause pachyonychia congenita type 1 (PC-1), while mutations in KRT16 or KRT6C underlie focal palmoplantar keratoderma (FPPK). A new classification system of PC has been adopted based on the mutated gene. PC rarely presents the symptoms of diffuse plantar keratoderma. Mutation in the tail domain of keratins is rarely reported. PC combined with fissured tongue has never been described. OBJECTIVES: To investigate the genotype phenotype correlations between clinical features and gene mutational sites in two unrelated southern Chinese PC pedigrees (one family presented with specific fissured tongue, the other with diffuse plantar keratoderma). MATERIALS & METHODS: The whole coding regions of the KRT6A/KRT16/KRT17/KRT6B genes were amplified and directly sequenced to detect the mutation. To confirm the effect of the IVS8-2A>C mutation in KRT6A at the mRNA level, total RNA from the plantar lesion of a patient was extracted and reverse-transcribed to cDNA for sequence analysis. RESULTS: Two novel de novo mutations, a splice acceptor site variant IVS8-2A>C (p.S487FfsX72) in KRT6A and a heterozygous substitution c.AA373_374GG (p.N125G) within exon 1 of KRT16, were found separately in the two PC families. CONCLUSION: Genotype-phenotype correlations among PC patients with codon-125 mutation in KRT16 were established, while the phenotypes caused by the IVS8-2A>C mutation in KRT6A need further studies to confirm the rare feature of fissured tongue. PMID- 22668562 TI - Subacute default mode network dysfunction in the prediction of post-stroke depression severity. AB - PURPOSE: To identify patterns of rest functional connectivity (FC) in the whole brain with the default mode network (DMN) soon after stroke and to explore the predictive accuracy of the strength of rest FC in specific areas on poststroke severity of depression and anxiety symptoms. MATERIALS AND METHODS: The protocol was accepted by the local ethics board, and all patients provided informed consent to participate. Resting-state functional magnetic resonance (MR) images were acquired 10 days after a first stroke in 24 patients without a history of psychiatric illness. Independent component analysis was used to isolate the DMN in each subject. Hamilton Depression Rating Scale (HDRS) 17 and Hamilton Anxiety Rating Scale (HARS) were recorded 10 days and 3 months after the stroke. Associations between severity of anxiety or depression symptoms and DMN functional connectivity were investigated with whole-brain analyses by using statistical parametric mapping software and were adjusted for age, sex, manual laterality, and National Institutes of Health Stroke Severity scores. Correlations were considered significant if P<.001, with a cluster size of more than 50 voxels. RESULTS: Ten days after stroke, anxiety severity was correlated with functional connectivity in the middle temporal cortex and the anterior midcingulate cortex, while at 3 months after stroke, a correlation was observed with the middle temporal cortex and the posterior cingulate cortex. Poststroke depressive symptom severity did not correlate with functional connectivity changes at 10-day follow-up, while the HDRS 17 score was correlated with functional connectivity in the left middle temporal cortex and precuneus at 3 month follow-up. CONCLUSION: These results suggest that a dysfunction of DMN functional connectivity involved in emotional control is associated with the severity of poststroke depression. Further studies are necessary to determine the mechanisms of this functional impairment. PMID- 22668563 TI - Exposing exposure: automated anatomy-specific CT radiation exposure extraction for quality assurance and radiation monitoring. AB - PURPOSE: To develop and validate an informatics toolkit that extracts anatomy specific computed tomography (CT) radiation exposure metrics (volume CT dose index and dose-length product) from existing digital image archives through optical character recognition of CT dose report screen captures (dose screens) combined with Digital Imaging and Communications in Medicine attributes. MATERIALS AND METHODS: This institutional review board-approved HIPAA-compliant study was performed in a large urban health care delivery network. Data were drawn from a random sample of CT encounters that occurred between 2000 and 2010; images from these encounters were contained within the enterprise image archive, which encompassed images obtained at an adult academic tertiary referral hospital and its affiliated sites, including a cancer center, a community hospital, and outpatient imaging centers, as well as images imported from other facilities. Software was validated by using 150 randomly selected encounters for each major CT scanner manufacturer, with outcome measures of dose screen retrieval rate (proportion of correctly located dose screens) and anatomic assignment precision (proportion of extracted exposure data with correctly assigned anatomic region, such as head, chest, or abdomen and pelvis). The 95% binomial confidence intervals (CIs) were calculated for discrete proportions, and CIs were derived from the standard error of the mean for continuous variables. After validation, the informatics toolkit was used to populate an exposure repository from a cohort of 54 549 CT encounters; of which 29 948 had available dose screens. RESULTS: Validation yielded a dose screen retrieval rate of 99% (597 of 605 CT encounters; 95% CI: 98%, 100%) and an anatomic assignment precision of 94% (summed DLP fraction correct 563 in 600 CT encounters; 95% CI: 92%, 96%). Patient safety applications of the resulting data repository include benchmarking between institutions, CT protocol quality control and optimization, and cumulative patient- and anatomy-specific radiation exposure monitoring. CONCLUSION: Large scale anatomy-specific radiation exposure data repositories can be created with high fidelity from existing digital image archives by using open-source informatics tools. PMID- 22668564 TI - Reducing error and improving efficiency during vascular interventional radiology: implementation of a preprocedural team rehearsal. AB - PURPOSE: To determine the type and frequency of errors during vascular interventional radiology (VIR) and design and implement an intervention to reduce error and improve efficiency in this setting. MATERIALS AND METHODS: Ethical guidance was sought from the Research Services Department at Imperial College London. Informed consent was not obtained. Field notes were recorded during 55 VIR procedures by a single observer. Two blinded assessors identified failures from field notes and categorized them into one or more errors by using a 22-part classification system. The potential to cause harm, disruption to procedural flow, and preventability of each failure was determined. A preprocedural team rehearsal (PPTR) was then designed and implemented to target frequent preventable potential failures. Thirty-three procedures were observed subsequently to determine the efficacy of the PPTR. Nonparametric statistical analysis was used to determine the effect of intervention on potential failure rates, potential to cause harm and procedural flow disruption scores (Mann-Whitney U test), and number of preventable failures (Fisher exact test). RESULTS: Before intervention, 1197 potential failures were recorded, of which 54.6% were preventable. A total of 2040 errors were deemed to have occurred to produce these failures. Planning error (19.7%), staff absence (16.2%), equipment unavailability (12.2%), communication error (11.2%), and lack of safety consciousness (6.1%) were the most frequent errors, accounting for 65.4% of the total. After intervention, 352 potential failures were recorded. Classification resulted in 477 errors. Preventable failures decreased from 54.6% to 27.3% (P < .001) with implementation of PPTR. Potential failure rates per hour decreased from 18.8 to 9.2 (P < .001), with no increase in potential to cause harm or procedural flow disruption per failure. CONCLUSION: Failures during VIR procedures are largely because of ineffective planning, communication error, and equipment difficulties, rather than a result of technical or patient-related issues. Many of these potential failures are preventable. A PPTR is an effective means of targeting frequent preventable failures, reducing procedural delays and improving patient safety. PMID- 22668565 TI - [Nobel Prizes 2011: dendritic cells, toll-like receptors and their contribution to fundamental and translational medicine]. PMID- 22668566 TI - [Gaps between prescription of anti-hypertensive and hypertension control in older adults of Buenos Aires suburbs]. AB - BACKGROUND: Medications delivered to primary care centers (PCC) all over the country through the Remediar program (RP) covers 80% of the most prevalent diseases. Among them, the prevalence of hypertension is 77% of 65 years or older. OBJECTIVE: To describe the pharmacological treatment and its appropriateness, and to understand needs and barriers among hypertensive beneficiaries of RP at Buenos Aires suburbs. Method Qualitative-quantitative triangulation: cross-sectional study with revision of medical records (MR) and in-depth interviews between December/2008 and February/2009 to hypertensive patients of 65 years or older and CAPS's staff. Prevalence of correct treatment (CT); appropriate Indication (AI); Optimal control (OC) were analyzed. RESULTS: The following PCCs were selected: Moreno, Tigre, Lomas de Zamora, Lanus and San Isidro. Prevalence of: CT: (10.2%; 95%CI 6,7-15,1); AI: (84.8%; 95% CI 80-89 ), and OC: 11,6% (95%CI 7-16) and OC among patients with good registry: 35.7% (95%CI 24,9-48,1). Eighty two % of patients received a prescription for enalapril. Deficient registry was detected in MR. Interviewees expressed difficulties in accessing treatment, lack of medication and use of alternative circuits to get them. Both, staff and patients were exposed to barriers generated by CAPSs and RP. CONCLUSIONS: A low degree of blood pressure control was observed, even with adequate prescription. Multifactorial problems explain several barriers to access and maintain hypertension treatment. PMID- 22668567 TI - [Reproducibility and reliability of a 4-day HBPM protocol with and without first day measurements]. AB - HBPM guidelines state that morning and evening measurements should be recorded and, to improve stability, the first day of measurements should be discarded. Our objective was to assess the reproducibility and reliability of a 4-day HBPM protocol with and without first day measurements. We analyzed a retrospective cohort of ambulatory patients who required a HBPM for diagnostic purposes or evaluation of treatment efficacy. A 4-day protocol was implemented, with daily duplicate measurements in the morning, afternoon and evening, using an OMRON 705 CP validated equipment. HBPM reproducibility was quantified by test-re-test correlations and standard deviation of differences (SDD) between BP measurements obtained during the entire 4 days, with and without exclusion of the first day. The reliability criterion was the stabilization of the mean and standard deviation (SD). We included 353 subjects with a total of 8224 BP recordings (median of 24 recordings per patient). We found a strong test-re-test correlation between days 1 to 4, which improved when we excluded the first day (p<0.001). We also found a reduction of the mean BP when we increased the number of days and a reduction of SDD when we excluded day 1. Therefore, we conclude that the exclusion of the first day of measurements improves the reproducibility and reliability of a 4-day protocol, and such two factors are not affected by the inclusion of afternoon measurements. PMID- 22668568 TI - [New insights into pathophysiology and treatment in Chagas-Mazza disease]. PMID- 22668569 TI - [Spontaneous mediastinal hematoma as initial presentation of cystic adenoma of ectopic parathyroid]. AB - Spontaneous mediastinal hematoma as initial presentation of cystic adenoma of ectopic parathyroid Atraumatic spontaneous mediastinal hematomas are uncommon. They are secondary to trauma, rupture of great vessels or heart and associated to iatrogenic events. We report a case of a 61 year-old woman who consults for mediastinal hematoma without previous trauma. Imaging studies ruled out cardiac or vascular lesions. At exploratory thoracotomy, a large mediastinal hematoma was evidenced without obvious mass or bleeding vessel. The material sent to the Pathology service was diagnosed as cystic adenoma of ectopic parathyroid gland. Mediastinal hematomas are related to traumatic causes, cardiac or great vessels rupture or iatrogenic proceedings. Once these causes are ruled out, an injury of ectopic parathyroid tissue must be considered in the differential diagnosis because mediastinum is the most frequent ectopic location. Histopathological and immunohistochemical studies are useful in determining the cause-related hematoma, as in this case determined the parathyroid origin of the lesion, and to rule out involvement by other tumors. PMID- 22668570 TI - [Colonic haematoma]. PMID- 22668571 TI - Rotator cuff injuries in adolescent athletes. AB - The cause of rotator cuff injuries in the young athlete has been described as an overuse injury related to internal impingement. Abduction coupled with external rotation is believed to impinge on the rotator cuff, specifically the supraspinatus, and lead to undersurface tears that can progress to full-thickness tears. This impingement is believed to be worsened with increased range of motion and instability in overhead athletes. A retrospective review of seven patients diagnosed with rotator cuff injuries was performed to better understand this shoulder injury pattern. The type of sport played, a history of trauma, diagnosis, treatment method, and outcome were noted. Six patients were male and one was a female. Baseball was the primary sport for four patients, basketball for one, gymnastics for one, and wrestling for one. The following injury patterns were observed: two patients tore their subscapularis tendon, two sustained avulsion fractures of their lesser tuberosity, one tore his rotator interval, one tore his supraspinatus, and one avulsed his greater tuberosity. Only four patients recalled a specific traumatic event. Three patients were treated with arthroscopic rotator cuff repair, three with miniopen repair, and one was treated with rehabilitation. Six of the seven patients returned to their preinjury level of sport after treatment. Rotator cuff tears are rare in the adolescent age group. The injury patterns suggest that acute trauma likely accounts for many rotator cuff tears and their equivalents in the young patient. Adolescents with rotator cuff tears reliably return to sports after treatment. The possibility of rotator cuff tears in skeletally immature athletes should be considered. The prognosis is very good once this injury is identified and treated. PMID- 22668572 TI - Biological reconstruction of the femur using double free vascularized fibular autografts in a vertical array because of a large defect following wide resection of an osteosarcoma: a case report with 7 years of follow-up. AB - Free vascularized fibular autograft transfer to the defect area after wide resection of bone sarcoma is one of many biological reconstruction methods. We report on an 8-year-old girl with 7 years of follow-up treated for right femur osteosarcoma. A 26 cm long tumor was resected with clear margins. Because the length of one fibular autograft was shorter than the defect length, bilateral free vascularized fibular autografts were used in a vertical array on top of one another, and placed inside a fresh-frozen femoral allograft. The original length of the femur was maintained by this technique. PMID- 22668573 TI - Bilateral pathological dislocation of the hip secondary to tuberculous arthritis following disseminated tuberculosis: a case report and review of the literature. AB - Pathological dislocation of the hip has been reported as a complication in various hip disorders. Several pathomechanisms including capsular laxity, synovial hypertrophy, and acetabular and proximal femur destruction have been described. We report a case of bilateral pathological dislocation of the hip in a 6-year-old girl secondary to tuberculous arthritis following disseminated tuberculosis, which we managed operatively. At the 18-month follow-up, the child had a clinically stable left hip despite radiological subluxation. Bilateral pathological dislocation of the hip associated with tuberculous arthritis is a rare condition and has never been reported in the literature. PMID- 22668574 TI - Functional outcome following direct repair or intervertebral fusion for adolescent spondylolysis: a systematic review. AB - A systematic review of the literature was performed to establish whether direct repair of the pars defect or intervertebral fusion achieves better Oswestry Disability Index scores in adolescent spondylolysis or low-grade spondylolisthesis. Nine studies fulfilled the inclusion criteria, reporting a minimum total of 80 direct repairs and 108 fusions because of presumed replication of data between studies. Little statistically or clinically significant difference could be established between the two interventions. The only comparative study showed improved long-term outcome with fusion. Further well-designed prospective comparative studies are required to establish the optimum treatment for this condition. PMID- 22668575 TI - A proposal for improving multicolor FISH sensitivity in the diagnosis of malignant melanoma using new combined criteria. AB - Fluorescence in situ hybridization (FISH) for the diagnosis of melanoma makes use of specific fluorescent probes to detect selected chromosomal alterations on paraffin-embedded tissue samples. To date, interpretation of FISH data has been based on numerical values generated by 2 different computational algorithms that of Abbott and that of Gerami. To further evaluate the value of FISH in the diagnosis of malignant melanoma, we selected 163 clinically and histologically unequivocal cases of malignant melanoma in a cohort of 575 melanocytic tumors and analyzed FISH data using the criteria of Abbott, Gerami, and new combined criteria. Depending on the used criteria, FISH was positive in the unequivocal malignant melanoma in 69.3% (113/163) of cases using the Abbott criteria, 74.2% (121/163) of cases using the Gerami criteria, and 82.2% (134/163) of cases using the combined criteria of Abbott and Gerami. Although use of all 3 criteria was associated with 100% FISH negativity in a cohort of 30 unequivocal benign melanocytic nevi, use of the combined criteria revealed more FISH-positive cases in ambiguous benign melanocytic lesions than the criteria of Abbott or Gerami alone: Abbott, 125 of 367; Gerami, 146 of 367; combined, 161 of 367. Furthermore, we show that 66% (8/12) of FISH-negative cases of unequivocal melanoma are positive when analyzed by array comparative genomic hybridization (aCGH), demonstrating that false-negative results remain despite the usage of the combined criteria for evaluation of FISH data. In these 8 FISH-negative aCGH positive cases, copy number alterations were often located on chromosomes 9p, a chromosomal locus that is not targeted by the FISH probes currently used. In conclusion, the existing criteria for the evaluation of multicolor melanocytic FISH are limited by a nonnegligeable rate of false negativity that can be reduced by using newly proposed combined criteria but at the cost of increased detection of FISH positivity in ambiguous benign melanocytic lesions. PMID- 22668576 TI - Basal cell carcinoma with myoepithelial differentiation. PMID- 22668577 TI - Perineurial cells in granular cell tumors and neoplasms with perineural invasion: an immunohistochemical study. AB - Granular cell tumors (GCT) are nerve sheath neoplasms composed of Schwann cells with granular cytoplasm. Perineurial cells are the cellular component of the perineurium and of perineuriomas, neoplasms supposedly derived from perineurial cells. However, perineurial cells have also been found in other Schwann cell derived tumors. These cells have not been well studied in GCTs. We studied the presence of perineurial cells in a series of 24 GCTs with EMA, claudin-1, and Glut-1, which are immunohistochemical markers for perineurial cells. Three cases lacked nerve fascicles. Three cases showed no perineurial proliferation (grade 0), 7 showed grade 1 proliferation, and 11 showed grade 2 proliferation. For comparison, we studied 17 cases of neoplasms with perineural invasion (PNI): 7 cutaneous neoplasms [squamous cell carcinomas (n = 3), cutaneous lymphoma, malignant melanoma, eccrine carcinoma, congenital neurotropic nevus (n = 1 each)] and 10 noncutaneous tumors [prostatic (n = 2), gastric (n = 2), and colonic (n = 2) adenocarcinomas; invasive ductal carcinoma of breast (n = 2); urothelial carcinoma of bladder (n = 1); and oral squamous cell carcinoma (n = 1)] with the same antibodies for perineurial cells. We found perineurial cell proliferation in 10 cases, 6 grade 1, and 4 grade 2. These perineurial cells were limited to the areas around the nerve fascicles. Most of the tumor was devoid of perineurial cells. Thus, it was interpreted more as a hyperplastic or reactive phenomenon than a neoplastic component. Claudin-1 was the most sensitive of the 3 markers that we used. Such proliferation was less intense in non-GCTs. In conclusion, proliferation of perineurial cells in GCTs and neoplasms with PNI is a common finding that had not been previously studied. It seems to be a non-neoplastic phenomenon. PMID- 22668578 TI - Carcinoma erysipeloides of laryngeal origin. AB - The term "carcinoma erysipeloides" (CE) designates an uncommon form of cutaneous metastasis. CE is most often associated with carcinoma of the breast. However, there have been reports of CE from carcinoma of the uterus, prostate, lung, ovary, stomach, tonsils, thyroid, pancreas, rectum, parotid glands and melanoma. To our knowledge, CE of laryngeal origin has not been previously reported. We describe a patient diagnosed with human immunodeficiency virus and hepatitis C virus coinfection who developed a supraglottic laryngeal squamous cell carcinoma and erythematous cutaneous lesions. A skin biopsy demonstrated invasion of dilated dermal lymphatics by clusters of atypical squamous cells with polymorphic nuclei and extensive infiltration of the dermis by tumor cells. The histology of the metastatic cells was similar to that of the laryngeal carcinoma. PMID- 22668579 TI - MITF accurately highlights epidermal melanocytes in atypical intraepidermal melanocytic proliferations. AB - Atypical intraepidermal melanocytic proliferations (AIMP) have random cytologic atypia and other histologic features that are concerning for malignancy and often require immunohistochemistry to differentiate from melanoma in situ. Immunostaining with S100, Melan-A, and microphthalmia-associated transcription factor (MITF) was performed for 49 morphologically well-characterized AIMP lesions. The percentage of cells in the basal layer of the epidermis that were identified as melanocytes by immunohistochemistry was compared with the percentage observed by morphology on hematoxylin and eosin staining, which is the gold standard stain for identifying cytologic atypia within an AIMP. Melan-A estimated the highest percentage of melanocytes and S100 the fewest in 47 of the 49 lesions examined. The estimated percentage of melanocytes was 23.3% (95% confidence interval: 18.6-28.1; P < 0.001) higher for Melan-A compared with hematoxylin and eosin staining. Melanocyte estimates were similar for hematoxylin and eosin and MITF (P = 0.15) although S100 estimated 21.8% (95% confidence interval: -27.2 to -16.4; P < 0.001) fewer melanocytes than hematoxylin and eosin. Melan-A staining produces higher estimates of epidermal melanocytes than S100 and MITF, which may increase the likelihood of diagnosing melanoma in situ. In contrast, melanoma in situ may be underdiagnosed with the use of S100, which results in lower estimates of melanocytes than the other 2 immunostains. Therefore, the best immunohistochemical marker for epidermal melanocytes is MITF. PMID- 22668580 TI - Corneal endothelial damage in the relatively thin cornea after collagen cross linking treatment. PMID- 22668582 TI - Vascular endothelial growth factor inhibitors for treatment of corneal neovascularization: a meta-analysis. AB - PURPOSE: To evaluate the therapeutic effect of bevacizumab (Avastin) on corneal neovascularization (NV). METHODS: Systematic review and meta-analysis of the literature was performed. Seven eligible clinical human studies and 18 eligible experimental animal studies examining the effectiveness of bevacizumab treatment on corneal NV were included in the meta-analysis. Pertinent publications were identified through a systematic search of PubMed. All references of relevant reviews and eligible articles were also screened, and data were extracted from each eligible study. The random-effects model (of DerSimonian and Laird) was used to combine the results from the selected studies. Heterogeneity was explored using available data. Publication bias was also assessed. RESULTS: A significant reduction of corneal neovascularized area was seen in clinical human studies, with a pooled reduction of 36% [95% confidence interval (CI), 18%-54%] overall, of 32% (95% CI, 10%-54%) for subconjunctival anti-vascular endothelial growth factor injections, and 48% (95% CI, 32%-65%) for topical treatment. Pooled mean change in best-corrected visual acuity showed an improvement in best-corrected visual acuity by 0.04. The summary standardized mean difference in animal studies indicated a statistically significant reduction in the area of corneal NV when treated with bevacizumab compared with the control group by -1.71 (95% CI, -2.12 to -1.30). The subtotal pooled standardized mean differences were -1.83 (95% CI, 2.38 to -1.28) for subconjunctival anti-vascular endothelial growth factor injections and -1.50 (95% CI, -1.88 to -1.12) for topical treatment. CONCLUSION: Our results suggest that both topical and subconjunctival bevacizumab achieve significant reduction in the area of corneal NV. This meta-analysis provides an evidential basis for the new therapeutic concept of treating corneal NV with antiangiogenic therapy. PMID- 22668583 TI - Changes in corneal biometry and the associated histology in rhesus monkeys wearing orthokeratology contact lenses. AB - PURPOSE: This study compared the effect of orthokeratology (OK) lens wear on corneal topography and microstructure between the 1-night and 30-night wearers to predict any adverse responses of the eyes to long-term OK lens wear. METHODS: Nine rhesus monkeys with one eye wearing an OK lens and the fellow eye wearing a rigid gas permeable (RGP) lens were used in this study. The lenses were worn for 11 hours, with the measurement of corneal curvature and thickness and axial components of the eye at 0 night (n = 9), 1 night (n = 9), and 30 nights (n = 6). Histology was performed at 1 and 30 nights of lens wear. RESULTS: Corneal surface power in the 3-mm central region was reduced in the OK eye when compared with the RGP eye (P < 0.05). Central corneal thickness was only reduced in 30 nights of OK lens wear (P < 0.05). Under light microscopy, the 1-night OK or RGP eyes showed normal morphology in all layers of the cornea. The 30-night OK eyes showed a thinned central corneal epithelium and a thickened but less stratified paracentral corneal epithelium when compared with the 30-night RGP eyes. Under electron microscopy, intercellular junctions of corneal epithelium in the 30 night OK eyes were much looser than those in the 1-night OK eyes. However, the density and morphology of hemidesmosomes were similar between the OK and RGP eyes at 30 nights of lens wear. CONCLUSIONS: Overnight OK can change the corneal curvature through anterior corneal remodeling, resulting in an effective correction of myopia. However, a decrease in intercellular junctions during long term wear may compromise the functions of the corneal epithelium as a border mechanical barrier. PMID- 22668581 TI - Topical azithromycin and oral doxycycline therapy of meibomian gland dysfunction: a comparative clinical and spectroscopic pilot study. AB - PURPOSE: Meibomian gland dysfunction (MGD) is a common clinical problem that is often associated with evaporative dry eye disease. Alterations of the lipids of the meibomian glands have been identified in several studies of MGD. This prospective, observational, open-label clinical trial documents the improvement in both clinical signs and symptoms of disease as well as spectroscopic characteristics of the meibomian gland lipids after therapy with topical azithromycin ophthalmic solution and oral doxycycline treatment. METHODS: Subjects with symptomatic MGD were recruited. Signs of MGD were evaluated with a slit lamp. Symptoms of MGD were measured by the response of subjects to a questionnaire. Meibum lipid-lipid interaction strength, conformation, and phase transition parameters, and meibum protein content were measured using Fourier transform infrared spectroscopy and principal component analysis. Terpenoids, short-chain CH3 moieties, lipid oxidation, wax, cholesterylesters and glycerides were measured with a proton nuclear magnetic resonance (H-NMR) spectrometer. RESULTS: Topical therapy with azithromycin and oral therapy with doxycycline relieved signs and symptoms and restored the lipid properties of the meibomian gland secretion toward normal. Compared with 4 weeks of azithromycin treatment reported in our previous study, oral doxycycline treatment was slightly less effective in improving foreign body sensation and the signs of plugging and secretion. In subjects with clinical evidence of MGD, changes in ordering of the lipids and phase transition temperature were brought closer to normal with azithromycin treatment than doxycycline treatment. Treatment with doxycycline but not azithromycin restored the Fourier transform infrared spectroscopy-principal component analysis scores and relative area of the H-NMR resonance at 1.26 ppm. Both doxycycline and azithromycin treatment restored the levels of the relative areas of the H-NMR resonance at 5.2 and 7.9 ppm to normal levels. The levels of meibum protein and meibum lipid oxidation were not influenced by azithromycin or doxycycline treatment. CONCLUSIONS: The mechanism of action of doxycycline may be different from that of azithromycin in therapy of MGD. It is notable that when carotenoids in meibum are low, as in MGD, the tear film is unstable and patients have the signs and symptoms of dry eyes. When carotenoids are restored with azithromycin and doxycycline treatment, tear film stability is restored and patients no longer have the signs and symptoms of dry eyes. PMID- 22668584 TI - Ocular surface stem cell transplantation rejection: incidence, characteristics, and outcomes. AB - PURPOSE: To describe the incidence, characteristics, risk factors, treatment, and outcomes of ocular surface stem cell transplantation (OSST) rejection. METHODS: A chart review of patients who had OSST at a single institution between 1998 and 2010 was performed. Data were collected on patient demographics, type of OSST procedure, duration of immunosuppression, and rejection characteristics. Main outcome measures were ocular surface stability and improvement in best-corrected visual acuity. RESULTS: Two hundred twenty-two eyes of 158 patients were included with mean follow-up of 62.7 months (range, 12.0-158.3 months). The most common indications for OSST were aniridia (46.4%), chemical/thermal injury (22.1%), and Stevens-Johnson syndrome (12.2%). The most common procedures performed were keratolimbal allograft (KLAL) alone (80.6%) and combined living-related conjunctival allograft (lr-CLAL)-KLAL (11.3%). Mean time on immunosuppression was 44.3 months (range, 7.6-138.2 months). Severe rejection occurred in 43 eyes (19.4%) with mean time to rejection being 15.2 months (range, 0.2-93.1 months). Low-grade rejection occurred in 26 eyes (11.7%) with mean time to rejection being 26.2 months (range, 1.3-64.9 months). At the final follow-up, 36.6% of eyes in the rejection group achieved a stable ocular surface compared with 71.9% of eyes in the nonrejection group (P < 0.0001). Risk factors associated with increased risk of rejection were younger age (P < 0.0001), KLAL alone (P = 0.049), and noncompliance with immunosuppression (P = 0.047). CONCLUSIONS: Ocular surface outcomes for patients with OSST rejection are poor, with the majority of patients having failed ocular surfaces despite treatment with increased immunosuppression and repeat OSST. It is critical for success that OSST patients are closely monitored for rejection and for compliance with immunosuppression. PMID- 22668585 TI - Association of gender, ABCA1 gene polymorphisms and lipid profile in Greek young nurses. AB - OBJECTIVE: One of the important proteins involved in lipid metabolism is the ATP binding cassette transporter A1 (ABCA1) encoding by ABCA1 gene. In this study we evaluated the single nucleotide polymorphisms (SNPs) of ABCA1 gene. We analyzed SNPs in chromosome 9 such as rs2230806 (R219K) in the position 107620867, rs2230808 (R1587K) in the position 106602625 and rs4149313 (I883M) in the position 106626574 according to gender and lipid profile of Greek nurses. METHODS: The study population consisted of 447 (87 men) unrelated nurses who were genotyped for ABCA1 gene polymorphisms. Additionally, lipid profile [total cholesterol, triglycerides, high density lipoprotein cholesterol, low density lipoprotein cholesterol (LDL-C) and apolipoprotein A1] was evaluated. RESULTS: The distribution of all three studied ABCA1 gene polymorphisms did not differ according to gender. However, only R219K genotype distribution bared borderline statistical significance (p = 0.08) between the two studied groups. Moreover, allele frequencies of R219K, R1587K and I88M polymorphisms did not differ according to gender. In general, blood lipid levels did not seem to vary according to ABCA1 gene polymorphisms, when testing all subjects or when testing only men or only women. However, a significant difference of LDL-C distribution was detected in all subjects according to R1587K genotype, indicating lower LDL-C levels with KK polymorphism (p = 0.0025). The above difference was solely detected on female population (p = 0.0053). CONCLUSIONS: The ABCA1 gene polymorphisms frequency, distribution and lipid profile did not differ according to gender. However, in the female population the KK genotype of R1587K gene indicated lower LDL-C levels. Further studies, involving a higher number of individuals, are required to clarify genes and gender contribution. PMID- 22668586 TI - Building a better safety net: taking the safety agenda to office-based women's health. AB - The recent focus on health care safety is a response to the central ethical tenet of medicine--to do no harm. The delivery of safe hospital care has led to demonstrable reductions in medical errors, adverse events, and patient injuries. These improvements have led to a commensurate reduction of legal risk and the emotional toll on caregivers as well as families. It also has reinvigorated the reason many physicians went into medicine--to make a difference for women's health. The new, voluntary Safety Certification in Outpatient Practice Excellence (SCOPE) for Women's Health program of the American Congress of Obstetricians and Gynecologists is a means to both evaluate and recognize work in a critical but often neglected arena--the outpatient setting. It builds on infrastructure created for safety programs in hospital settings. Strong physician leadership, the development of an office culture committed to safety, communication and teamwork skills, safety programs for office-based surgery, medication safety, and tracking systems are all important for safe treatment of our patients in the office setting. The SCOPE Program defines the necessary safety goals for ambulatory women's health care and provides an educational pathway to reach those goals. SCOPE certification is an achievement recognizing the commitment of physicians and their staff to the health and safety of their patients. PMID- 22668587 TI - [Editorial comment. Thematic issue: Pulmonary medicine]. PMID- 22668588 TI - [Early and late mortality of patients with community acquired pneumonia]. AB - Community acquired pneumonia is the most frequent infective cause of severe sepsis and death. The risk of mortality in community acquired pneumonia is predictable by the "pneumonia severity index" and various biomarkers (e.g., procalcitonin, troponin-I). Quantitative testing of pneumococcal load (DNA) in blood has also become possible recently. Early death due to acute myocardial infarction is more frequent among patients with previous community acquired pneumonia. The 1-year and the 5-6 year survival is shorter among these patients. Pro-inflammatory cytokines synthesized during community acquired pneumonia accelerate chronic inflammation ongoing in atherosclerotic plaques. The pro thrombotic condition present in atherosclerosis is also potentiated by community acquired pneumonia. These pathophysiological mechanisms may explain the epidemiologic fact that community acquired pneumonia is an independent risk factor of cardiovascular mortality. PMID- 22668589 TI - [Simultaneous occurrence of chronic obstructive pulmonary disease and obstructive sleep apnea: the overlap syndrome]. AB - Obstructive sleep apnea syndrome is a common disorder in adults associated with several cardiovascular diseases and impaired quality of life. Chronic obstructive pulmonary disease is also a common clinical condition in middle-aged adults. The combination of these two conditions can eventuate a severe combined sleep-related breathing disorder. It is important to recognize coexisting sleep apnea in patients with chronic obstructive pulmonary disease in time and to treat it appropriately. PMID- 22668590 TI - [Pulmonary infections following solid organ transplantation]. AB - Solid organ transplantation is the standard of care for selected patients with severe vital organ dysfunction. The need for immunosuppression to prevent organ rejection is a common characteristic of recipients. Immunosuppression increases the risk of infections, especially with low virulence opportunistic pathogens. Infections following solid organ transplantation mainly affect the lungs and the airways. Establishing the diagnosis includes a wide spectrum of pulmonary diagnostics, high standard microbiological analysis and various imaging methods. With the improvement of treatment options, the number of kidney, liver, heart and lung transplant recipients is increasing and, therefore, more and more physicians may meet pulmonary complications in these patients. PMID- 22668591 TI - [Screening for lung cancer]. AB - The authors give an overview about the novel results and shifting paradigm of lung cancer screening. They also summarize the results of previous and most recent clinical trials, which re-directed the international interest on lung cancer screening. PMID- 22668592 TI - [Personalized therapy in non-small cell lung cancer: from diagnosis to therapy]. AB - Molecular targeted treatment, with broadening opportunities, plays an important role in the management of lung cancer patients, which renders molecular mapping of the tumor tissue crucial. In case of cytotoxic chemotherapy, there is no patient selection according to tissue biomarkers; however, there are expanding results that might help oncologists to use personalized chemotherapy in the near future. This may be of great importance when patients' age, performance status and/or co-morbidity make the applicability of chemotherapy uncertain. Nowadays, molecular targeted treatment gives hope mainly for patients with adenocarcinoma; however, promising therapeutic targets have already been outlined due to intensive research. In these days, we are experiencing a turbulent era of onco pulmonology, which - despite all difficulties - gives hope for both patients and clinicians. PMID- 22668593 TI - [Non-invasive respiratory unit in the Hungarian health care system]. AB - Treating patients with acute or chronic respiratory insufficiency still poses a major load on the healthcare system. Though there is evidence that treating these patients in high dependency respiratory units results in a shortening of hospital stay, reduces the need of intubation, and decreases mortality. In the Hungarian routine these patients are treated in general wards until the development of global respiratory insufficiency, when they are transferred to intensive care units. The authors present their first year experience on their novel Non invasive Respiratory Unit established at Semmelweis University. PMID- 22668595 TI - Scale-up of isoniazid preventive therapy in PEPFAR-assisted clinical sites in South Africa. AB - We reviewed the implementation of isoniazid preventive therapy (IPT) in South Africa from January 2010 to March 2011. The South African National Department of Health distributed revised IPT guidelines in May 2010 to increase IPT use in eligible human immunodeficiency virus (HIV) infected patients. We found a dramatic increase in the absolute numbers of patients reported to have been initiated on IPT (from 3309 in January-March 2010 to 49 130 in January-March 2011), representing an increase in the proportion (1.0-10.5%) of potentially eligible HIV-infected patients started on IPT. PMID- 22668596 TI - Caries resistance as a function of age in an initially caries-free population. AB - Using data from the Center for Oral Health Research in Appalachia Study, we examined variability in susceptibility to dental caries among children and adolescents in rural Appalachia. Among 210 participants who were caries-free at the initial visit, age at the baseline visit can be used as a proxy for the degree of caries resistance; probability of caries development at the tooth level decreased as age at the baseline visit increased. Participants who stayed caries free for a longer period during childhood and adolescence experienced less extensive caries, as measured by the number of carious teeth. However, the probability of becoming caries-positive did not correlate with age at the baseline visit. For children between 1 and 18 years of age, there was not a "threshold age" after which a caries-free child's risk of caries onset is significantly reduced. PMID- 22668597 TI - Projection of non-peptidergic afferents to mouse tooth pulp. AB - A large proportion of pulpal nociceptors are known to contain neuropeptides such as CGRP. However, the projection of non-peptidergic nociceptors to tooth pulp is controversial. Recently, the non- peptidergic subset of nociceptors has been implicated in mechanical pain in the skin. Since mechanical irritation of pulpal nociceptors is critical for evoking tooth pain under pathophysiological conditions, we investigated whether the non-peptidergic afferents project to tooth pulp as potential mechanotransducing afferents. For clear visualization of the non-peptidergic afferents, we took advantage of a recently generated knock-in mouse model in which an axonal tracer, farnesylated green fluorescence protein (GFP), is expressed from the locus of a sensory neuron-specific gene, Mrgprd. In the trigeminal ganglia (TG), we demonstrated that GFP is exclusively expressed in afferents binding to isolectin B4 (IB4), a neurochemical marker of non peptidergic nociceptors, but is rarely co-localized with CGRP. Retrograde labeling of pulpal afferents demonstrated that a low proportion of pulpal afferents was co-localized with GFP. Immunohistochemical detection of the axonal tracer revealed that GFP-positive afferent terminals were densely projected into the tooth pulp. These results provide convincing evidence that non-peptidergic nociceptors are projected into the tooth pulp and suggest a potential role for these afferents in tooth pain. PMID- 22668598 TI - Photocatalytic degradation with immobilised TiO(2) of three selected neonicotinoid insecticides: imidacloprid, thiamethoxam and clothianidin. AB - This research focused on photocatalytic degradation of imidacloprid, thiamethoxam and clothianidin employing a tailor-made photoreactor with six polychromatic fluorescent UVA (broad maximum at 355 nm) lamps and immobilised titanium dioxide (TiO(2)) on glass slides. The disappearance was followed by high pressure liquid chromatography (HPLC-DAD) analyses, wherein the efficiency of mineralization was monitored by measurements of total organic carbon (TOC). Within 2h of photocatalysis, all three neonicotinoids were degraded following first order kinetics with rate constants k=0.035 +/- 0.001 min(-1) for imidacloprid, k=0.019 +/- 0.001 min(-1) for thiamethoxam and k=0.021 +/- 0.000 min(-1) for clothianidin. However, the rate of mineralization was low, i.e. 19.1 +/- 0.2% for imidacloprid, 14.4 +/- 2.9% for thiamethoxam and 14.1 +/- 0.4% for clothianidin. This indicates that several transformation products were formed instead. Some of them were observed within HPLC-DAD analyses and structures were proposed according to the liquid chromatography-electro spray ionization tandem mass spectrometry analyses (LC-ESI-MS/MS). The formation of clothianidin, as thiamethoxam transformation product, was reported for the first time. PMID- 22668599 TI - Ozonation as an advanced oxidant in treatment of bamboo industry wastewater. AB - The present study employed ozonation process to treat the bamboo industry wastewater (BIWW). The impact of ozone dosage and initial organic concentration on color, COD and TOC removal rates were studied along with characterization of the major organics in raw and treated wastewater. The results suggested the ozone dosage of 3.15 g h(-1) (concentration 52.5 mg L(-1)) was suitable for the treatment. After 25 min ozonation of 1L raw wastewater, the color, COD and TOC removal efficiencies were 95%, 56% and 40%, respectively, with an influent COD concentration of 835 mg L(-1). The ratio of kg O(3) kg(-1) COD at 3.15 g h(-1) was 2.8 (<3), revealing that ozonation was a cost effective process for tertiary treatment of BIWW. Longer oxidization time was required to achieve similar results for raw wastewater with higher COD concentration. The chromatogram from gel permeation chromatography revealed that ozonation resulted in the breakdown of high molecular weight compounds into lower molecular weight components but could not completely mineralize the organic matter. The majority of these compounds were identified in both raw and ozonated samples via GC-MS analysis. In addition to ester derivatives as the main intermediates of ozonation, 1 chloroctadecane, methyl stearate, benzophenone and alpha-cyperone were identified as the by-products of ozonation. PMID- 22668600 TI - Mono-/dihydroxybenzoic acid esters and phenol pyridinium derivatives as inhibitors of the mammalian carbonic anhydrase isoforms I, II, VII, IX, XII and XIV. AB - Using hydroxy-/dihydroxybenzoic acids as leads, a series of methyl, ethyl and iso propyl esters of 4-hydroxy-benzoic acid, 2,4-, 2,5-, 2,6-, 3,4-, and 3,5 dihydroxybenzoic acids and of coumaric acid, were obtained and investigated for the inhibition of six mammalian carbonic anhydrase (CA, EC 4.2.1.1) isoforms, that is, the cytosolic CA I, II and VII, and the transmembrane CA IX, XII and XIV, many of which are established drug targets. Other compounds incorporating phenol/catechol moieties were obtained from dopamine by reaction with fluorescein isothiocyanate or with 2,4,6-trisubstituted pyrylium salts. Some aminophenols were also derivatized in a similar manner, by using pyrylium salts. Many of these compounds showed increased inhibitory action compared to the lead compounds from which they were obtained, with efficacy in the submicromolar range against most investigated CA isoforms. As phenols are a class of less investigated CA inhibitors (CAIs) compared to the sulfonamides, and their mechanism of inhibition is less well understood, compounds of the type designed here may be helpful in gaining more insights into these phenomena. PMID- 22668601 TI - Thiol-reactive compounds from garlic inhibit the epithelial sodium channel (ENaC). AB - The epithelial sodium channel (ENaC) is a key factor in the transepithelial movement of sodium, and consequently salt and water homeostasis in various organs. Dysregulated activity of ENaC is associated with human diseases such as hypertension, the salt-wasting syndrome pseudohypoaldosteronism type 1, cystic fibrosis, pulmonary oedema or intestinal disorders. Therefore it is important to identify novel compounds that affect ENaC activity. This study investigated if garlic (Allium sativum) and its characteristic organosulfur compounds have impact on ENaCs. Human ENaCs were heterologously expressed in Xenopus oocytes and their activity was measured as transmembrane currents by the two-electrode voltage clamp technique. The application of freshly prepared extract from 5g of fresh garlic (1% final concentration) decreased transmembrane currents of ENaC expressing oocytes within 10 min. This effect was dose-dependent and irreversible. It was fully sensitive to the ENaC-inhibitor amiloride and was not apparent on native control oocytes. The effect of garlic was blocked by dithiothreitol and l-cysteine indicating involvement of thiol-reactive compounds. The garlic organosulsur compounds S-allylcysteine, alliin and diallyl sulfides had no effect on ENaC. By contrast, the thiol-reactive garlic compound allicin significantly inhibited ENaC to a similar extent as garlic extract. These data indicate that thiol-reactive compounds which are present in garlic inhibit ENaC. PMID- 22668602 TI - An analysis of implantable cardiac device reliability. The case for improved postmarketing risk assessment and surveillance. AB - Implantable cardiac devices have become the mainstay of the treatment of patients with heart disease. However, data regarding their reliability and, inferentially, safety have been called into question. We reviewed annual reports submitted to the Food and Drug Administration Office of Device Evaluation by device manufacturers from 2003 to 2007. The annual number of implantable cardiac defibrillators (ICDs) and cardiac resynchronization therapy defibrillator (CRT-D) implants, explants, and returned devices were tabulated along with the cumulative (Cum) number of implants for each device. We derived an annual explantation rate (AER) defined as the ratio of the annual number of explants less the number of normal battery depletions/Cum (*1000). From 2003 to 2007, 256,392 CRT-D and 459,300 ICD devices were implanted in the United States. The overall mean (+/-SD) AERs for ICD and CRT-D devices were, respectively, 49.5 (15.6) per 1000 ICD devices and 82.6 (35.5) per 1000 CRT-D devices. The AER for each device type significantly decreased over the study period (P for trend <0.001) although the AER for CRT-D devices was 38% higher than that for ICD devices (P < 0.001). On average, 20.3% of CRT-D devices and 22.6% of ICD devices were returned to the manufacturer for analysis after explantation. The rates of explanted CRT-D and ICD devices decreased from 2003 to 2007. Notwithstanding this favorable trend, the AER for CRT-D devices was higher than that for ICD devices. Improved methods for tracking individual device histories are needed for more precise estimates of the risk of device explantation for suspected malfunction. The proportion of devices returned to the manufacturer is suboptimal and needs to be improved to better understand the mechanisms of device malfunction. PMID- 22668603 TI - From the editor: primary health care in Europe. PMID- 22668604 TI - Primary care in Europe: entering the age of austerity. AB - Many European countries have well-developed health systems that offer universal access to health services and which have a strong primary care sector. However, as the financial crisis in Europe progresses, it is leading to significant cutbacks in publicly funded health services. A key objective for primary care physicians will therefore be to work in an environment where resources will be much more limited than in the past. In the longer term, the role of primary care physicians in European health systems will continue to expand to meet the aim of shifting health services to the generally more cost-effective setting of primary care. PMID- 22668605 TI - An answer to chronicity in the Basque Country: primary care-based population health management. AB - Chronic conditions have an impact on individuals since they represent a restraint on quality of life, functional status, and productivity of people who suffer from them but they also compromise the sustainability of health systems. In 2010, the Strategy for Tackling the Challenge of Chronicity in the Basque Country was published. It contains policies and projects aimed at reinventing the health delivery model with the purpose of improving the quality of care for chronic patients and advancing toward a more sustainable, proactive, and integrated model. We present 3 projects here: population stratification, integrated care initiatives, and innovation from health care staff. PMID- 22668606 TI - A sustainable primary care system: lessons from the Netherlands. AB - The Dutch primary care system has drawn international attention, because of its high performance at low cost. Primary care practices are easily accessible during office hours and collaborate in a unique out-of-hours system. After the reforms in 2006, there are no copayments for patients receiving care in the primary care practice in which they are registered. Financial incentives support the transfer of care from hospital specialists to primary care physicians, and task delegation from primary care physicians to practice nurses. Regional collaborative care groups of primary care practices offer disease management programs. The quality assessment system and the electronic medical record system are predominantly driven by health care professionals. Bottom-up and top-down activities contributed to a successful Dutch primary care system. PMID- 22668607 TI - Ambulatory care trends in Germany: a road toward more integration of care? AB - Traditionally, Germany has a weak primary care system. In addition, the number of general practitioners (GPs) has declined in the past years. Main challenges are an aging population, disintegration of care, variations in care, an increase in chronic conditions, and a shortage of GPs especially in rural areas. Policy reacted by implementing financial incentives for GPs in rural areas and special GP training programs. Improvements in chronic care aim to better integrate care through Disease Management Programs, the electronic health card, and voluntary primary care schemes. The largest challenge to be addressed is the delegation of physician tasks to physician assistants. PMID- 22668608 TI - The commissioning reforms in the English National Health Service and their potential impact on primary care. AB - Reform of the National Health Service in England will increase power and responsibility for family doctors. They will have a larger role in planning and buying health care including control of substantial budgets. This article examines the likely implications of the proposed reforms for primary care, and in particularly for family doctors. This article considers the effect of the new clinical role in commissioning health care, changes to the accountability structures, and the effect on competition and integration within health services. It also considers the effect of new financial incentives and the possibility of creating conflicts of interest. PMID- 22668609 TI - The quality and outcomes framework in the United kingdom: indicators in transition. AB - The United Kingdom's pay-for-performance system, the Quality and Outcomes Framework, continues to evolve. Since its inception in 2004, the Quality and Outcomes Framework has provided a strong focus on evidence-based performance targets that remains a dominant theme. Strengthening of the evidence base has resulted in the appearance of several new clinical indicators. Increasingly, change has been driven by explicit public health goals with targets incentivized according to their potential for mortality reduction. In 2011, a new policy direction became apparent. New indicators accounting for almost 10% of the Quality and Outcomes Framework will be determined by achievement of targets reflecting the efficient use of health service resources. PMID- 22668610 TI - The nationwide systematic prevention of cardiovascular disease: the UK's health check programme. AB - High-income countries have witnessed marked reductions in cardiovascular disease (CVD) in recent years. Aging populations, however, maintain CVD as a major threat to public health and health system's financial stability. England has commenced on a population-wide screening and prevention program for CVD, the NHS Health Check program, the first national program of its type. We outline the program, its implications for public health and primary care, potential threats to the program, and its implications for the US health system. We conclude that the universal approach adopted contains a number of risks and uncertainties. The program's ongoing evaluation is vital and will provide internationally valuable data. PMID- 22668611 TI - The North West London Integrated Care Pilot: innovative strategies to improve care coordination for older adults and people with diabetes. AB - The North West London Integrated Care Pilot (ICP) was launched in June 2011 and brings together more than 100 general practices, 2 acute care trusts, 5 primary care trusts, 2 mental health care trusts, 3 community health trusts, 5 local authorities, and 2 voluntary sector organizations (Age UK and Diabetes UK) to improve the coordination of care for a pilot population of 550 000 people. Specifically, the ICP serves people older than 75 years and those with diabetes. Although still in the early stages of implementation, the ICP has already received national awards for its innovations in design and delivery. This article critically describes the ICP objectives, facilitating processes, and planned impact as well as the organizational and financial challenges that policy makers are facing in the implementation of the pilot program. PMID- 22668612 TI - Changes in preventable hospitalization patterns among the adults: a small area analysis of US states. AB - The study examines the variation and changes in preventable hospitalization (PH) rates across small areas over 1995-2005 in 5 US states for adults (aged 18-64 years). Using hospital discharge data from the Agency for Healthcare Research and Quality and contextual data from Health Resources and Services Administration, the study examines the role of managed care, primary care physician supply, and sociodemographic factors on adult PH rates. A stronger influence of minority and uninsured status, weaker contributions of managed care enrollment in the commercial as well as in the Medicaid markets, and weaker contributions of primary care density may have caused slower than expected reduction in adult PH rates. PMID- 22668613 TI - Medical home and emergency department utilization among children with special health care needs: an analysis of the 2005-2006 National Survey of Children with Special Health Care Needs. AB - The purpose of this article was to determine whether medical home associated with reduction in emergency department utilization by children with special health care needs. The study comprised 40 723 children participating in the National Survey of Children with Special Health Care Needs. For whole sample, presence of medical home was not associated with a decrease in emergency department (ED) utilization. However, children aged 0 to 5 years and those with severe functional limitations derived the most benefit from a medical home. Presence of medical home for severely limited children was associated with fewer ED visits (odds ratio, 0.59; 95% confidence interval, 0.50-0.70). Additional studies are warranted to explore specific components of a medical home and ED use. PMID- 22668614 TI - The "nuts and bolts" of implementing shared medical appointments: the Harvard Vanguard Medical Associates experience. AB - Harvard Vanguard Medical Associates (Harvard Vanguard) decided to develop a Shared Medical Appointment (SMA) program in 2007 for a variety of reasons. The program has launched 86 SMAs in 17 specialties at 12 sites and has exceeded 13 000 patient visits. Currently, the practice offers 54 SMAs and is believed to be the largest program in the country. This article provides an overview regarding staffing, space and equipment, project planning, promotional materials, training programs, workflow development, and the use of quality improvement (ie, LEAN) tools used to monitor the work to be completed and the metrics to date. PMID- 22668615 TI - Live and direct from the republic of Texas: TROT line. PMID- 22668616 TI - Welcome newly graduated oral and maxillofacial surgeons. PMID- 22668617 TI - White lesion on the dorsum of tongue. PMID- 22668618 TI - New oral anticoagulants: will they replace warfarin? AB - Vitamin K antagonists, such as warfarin, are considered to be the treatment of choice to prevent thromboembolic events, but problems, such as the need for frequent dose adjustment and monitoring of coagulation status, as well as multiple drug and food interactions, make their use difficult for both physician and patient. Two new anticoagulants are now being considered as possible replacements of vitamin K antagonists. Dabigatran, an oral direct thrombin inhibitor has already been approved in the USA for prevention of stroke in patients with atrial fibrillation. Rivaroxaban, a factor Xa inhibitor, and dabigatran are licensed in Europe and Canada for short-term thromboprophylaxis after elective hip or knee replacement surgery. The advantages of these drugs are that they are safe and effective, require no monitoring, have a direct mode of action against only one clotting factor (thrombin or factor Xa), have limited drug interactions, and have rapid peak blood levels. Based on the fact that dabigatran has already been approved for use in the USA, it would appear that it has an advantage over rivaroxaban in becoming the replacement drug for vitamin K antagonists. PMID- 22668619 TI - Validation of the Bitestrip versus polysomnography in the diagnosis of patients with a clinical history of sleep bruxism. AB - OBJECTIVE: This validation study compared an electromyography (EMG) device, Bitestrip, versus polysomnography in the diagnosis of sleep bruxism (SB). STUDY DESIGN: Forty-nine consecutive patients (32 women and 17 men, 41.2 +/- 12.9 years old) with a clinical history of SB were included in the study from the Orofacial Pain Clinic, Faculty of Dentistry, Pontifical Catholic University of Rio Grande do Sul in Brazil. RESULTS: Initially, we compared an SB positive/negative test result for both systems (agreement 87.8%, sensitivity 84.2%, positive predictive value 100%, and crude kappa 0.71). We then compared a 4-scale test (no, light, moderate, or severe bruxism) between the 2 methods (agreement 80.27%, weighted kappa 0.51, and Kendall W coefficient 0.575). CONCLUSIONS: The Bitestrip can be considered as a moderate screening method for the diagnosis of SB, because it is more precise in detecting the presence or absence of SB but less precise in detecting its intensity. PMID- 22668620 TI - Effectiveness of antiviral agents for the prevention of recurrent herpes labialis: a systematic review and meta-analysis. AB - OBJECTIVE: The purpose of this study was to complete a systematic review and, if possible, a meta-analysis on the effectiveness of systemic and topical nucleoside antiviral agents in the prevention of recurrent herpes labialis (RHL) in immunocompetent subjects. STUDY DESIGN: Multiple comprehensive electronic and manual literature searches without language restrictions identified the studies to be included. Quality assessment and data synthesis methods followed those described in the Cochrane guidelines. RESULTS: Of 2,683 papers reviewed, 10 met the inclusion criteria. Oral acyclovir (800-1,600 mg daily) and valacyclovir (500 mg daily for 4 months) were shown to be effective in the prevention of RHL when taken prior to the appearance of any symptoms or exposure to triggers. Of the 10 papers reviewed, only 1 was determined to have a low risk of bias. CONCLUSIONS: This review found support for the use of systemic acyclovir and valacyclovir for the prevention of RHL. PMID- 22668621 TI - Effect of salivary stimulation therapies on salivary flow and chemotherapy induced mucositis: a preliminary study. AB - OBJECTIVE: The objective of this study was to evaluate the effect of salivary stimulation therapies on the salivary flow, oral mucositis, and salivary cytokine levels in patients receiving allogeneic hematopoietic stem cell transplantation. STUDY DESIGN: Thirty-five eligible patients were randomized into 4 groups: control, mechanical sialogogue, transcutaneous electrical nerve stimulation (TENS) sialogogue, and combined mechanical/electrical sialogogue. Saliva was collected from patients before transplantation and at days 3, 7, and 14 after transplantation. The volume was measured and salivary cytokines were assessed using enzyme-linked immunosorbent assay. RESULTS: By day 14, resting and stimulated salivary flow levels were diminished. Resting salivary flow rates decreased the most in the control and mechanical groups. In contrast, TENS alone or in combination with mechanical stimulatory therapy benefited the patients. TENS-treated patients showed increase in resting salivary flow. Also, the groups treated with TENS had fewer patients affected by grades 3 and 4 mucositis, and less mucositis was associated with better patient survival (P = .027). CONCLUSIONS: TENS-associated salivary stimulation therapies minimized the reduction of salivary flow and prevented severe chemotherapy-induced oral mucositis. PMID- 22668622 TI - Amlexanox is as effective as dexamethasone in topical treatment of erosive oral lichen planus: a short-term pilot study. AB - OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of short-term and topical application of amlexanox paste in the treatment of erosive oral lichen planus (EOLP). STUDY DESIGN: A randomized, positive-controlled clinical trial was conducted from September 1 to December 31, 2009. Thirty-eight patients with EOLP received amlexanox paste (n = 20) or dexamethasone paste (n = 18) for 7 days. Outcome measures included size of erosive area and visual analog scale (VAS) scores. RESULTS: After 7 days of treatment, both groups showed significant reduction in erosive area and VAS scores (P < .001). There was no difference between groups in the reduction of erosive area (P = .937) and VAS scores (P = .161). None of the patients had severe adverse reactions. CONCLUSIONS: Topical application of amlexanox appeared as effective as dexamethasone in the treatment of EOLP and no serious side effects were found in this pilot study. PMID- 22668624 TI - Salivary adenocarcinoma, not otherwise specified: a clinicopathological study of 28 cases. AB - OBJECTIVE: The objective of this study was to summarize the clinicopathologic features of salivary adenocarcinoma, not otherwise specified (ANOS) and to evaluate current treatments. STUDY DESIGN: Between 1992 and 2010, 28 patients with ANOS were diagnosed and treated. Clinical data of demographic features, resection margin, neck dissection status, recurrence, and mortality were reviewed. RESULTS: The parotid had the most frequent incidence of ANOS and the palate was second. The peak onset was between 40 and 60 years. The preferred management modality was surgical intervention in all cases. Neck dissection and postoperative radiotherapy were performed in 67.9% and 64.3%, respectively. The mean survival time was 97 months. The 5- and 10-year overall survival rates were 62.2% and 36.0%, respectively. CONCLUSIONS: The current data demonstrate that T, N, M, and Union for International Cancer Control staging, resection margin, and neck dissection status are the most powerful predictors of survival. Long-term follow-up is required to identify possible late recurrence. PMID- 22668623 TI - Induction of apoptosis and up-regulation of cellular proliferation in oral leukoplakia cell lines inside electric field. AB - OBJECTIVE: In dentistry, metallic alloys are used for dentures, restorative materials, and orthodontic devices. Electric voltages up to 950 mV may occur between different dental alloys in the oral cavity. This study aimed to investigate physiologic reactions of oral leukoplakia cells in vitro to electric fields. STUDY DESIGN: A human leukoplakia cell line (MSK-LEUK1), cultivated in keratinocyte growth medium (KGM-2) supplemented with growth factors in 5% CO(2) humidified air at 37 degrees C, was exposed to electric field strength of 1-20 V/m for 24 hours in a custom-made pulse chamber. The cells were then analyzed for proliferation with the use of BrdU assay and for apoptosis with the use of TUNEL assay. Findings were assessed with the use of fluorescent microscopy. Ultrastructural changes were studied by transmission electron microscopy. RESULTS: Electric field strength of 1-10 V/m led to up-regulation of cell proliferation rate from 10.64% to 44.06% (P = .0001). The apoptotic index increased significantly (P = .0001) from 20.03% at 1 V/m to 46.56% at 10 V/m. Individual cell keratinization was seen in leukoplakia cells treated with 16 V/m. CONCLUSIONS: Oral galvanism induces subcellular changes in oral precancer cells in vitro that closely simulate some of the morphologic features of oral squamous cell carcinoma cells in vivo. PMID- 22668625 TI - Increased number of Langerhans cells in oral lichen planus and oral lichenoid lesions. AB - OBJECTIVE: The aim of this study was to quantify the presence of Langerhans cells (LC) in oral lichen planus (OLP) and oral lichenoid lesions (OLL), comparing them with normal epithelium. STUDY DESIGN: Thirty-six patients with biopsy-proven OLP or OLL were selected for the study, as well as 23 control subjects free of inflammatory conditions. Immunohistochemical reactions were performed using the streptavidin-biotin peroxidase complex method with CD1a and CD83 primary antibodies. Densities were compared between groups and correlated with microscopic findings. RESULTS: Patients with lichenoid conditions (OLP + OLL) presented higher densities of CD1a(+) cells than the control subjects (P = .03). Higher densities of CD1a were associated with a thinner layer of inflammatory cells (P = .02). CONCLUSIONS: This study indicates that OLP and OLL are characterized by the recruitment of LC, which may play a significant role on its pathogenesis. PMID- 22668626 TI - Comparison of Ki-67, cyclin E, and p63 in benign and malignant human pleomorphic adenoma. AB - OBJECTIVE: A set of cell proliferation-related molecular markers was used to detect the differences in proliferative activity between benign pleomorphic adenoma (PA) and carcinoma ex pleomorphic adenoma (CXPA). STUDY DESIGN: Seventy samples comprising 53 PAs, 10 noninvasive and 7 widely invasive (WI) CXPAs were selected. Immunohistochemical staining was used to detect Ki-67, cyclin E, and p63 expression. RESULTS: The average Ki-67 labeling index of WI CXPAs was higher than that of PAs and the malignant component of noninvasive CXPAs (M-noninvasive CXPA; P < .01). An increased cyclin E-positive staning was observed in M noninvasive CXPAs and WI CXPAs compared with PAs (P = .006). The p63 expression levels were notably decreased in M-noninvasive CXPAs and WI CXPAs compared with PAs (P = .007). CONCLUSIONS: The data support that increased or decreased expression of Ki-67, cyclin E, and p63 may indicate the proliferative differences between PA and CXPA. PMID- 22668627 TI - Computer-assisted orthognathic surgery: feasibility study using multiple CAD/CAM surgical splints. AB - OBJECTIVE: We present a virtual planning protocol incorporating a patented 3 surgical splint technique for orthognathic surgery. The purpose of this investigation was to demonstrate the feasibility and validity of the method in vivo. MATERIALS AND METHODS: The protocol consisted of (1) computed tomography (CT) or cone-beam computed tomography (CBCT) maxillofacial imaging, optical scan of articulated dental study models, segmentation, and fusion; (2) diagnosis and virtual treatment planning; (3) computed-assisted design and manufacture (CAD/CAM) of the surgical splints; and (4) intraoperative surgical transfer. Validation of the accuracy of the technique was investigated by applying the protocol to 8 adult class III patients treated with bimaxillary osteotomies. The virtual plan was compared with the postoperative surgical result using image fusion of CT/CBCT dataset by analysis of measurements between hard and soft tissue landmarks relative to reference planes. RESULTS: The virtual planning approach showed clinically acceptable precision for the position of the maxilla (<0.23 mm) and condyle (<0.19 mm), marginal precision for the mandible (<0.33 mm), and low precision for the soft tissue (<2.52 mm). CONCLUSIONS: Virtual diagnosis, planning, and use of a patented CAD/CAM surgical splint technique provides a reliable method that may offer an alternate approach to the use of arbitrary splints and 2-dimensional planning. PMID- 22668628 TI - Multidetector computerized tomographic fistulography in the evaluation of congenital branchial cleft fistulae and sinuses. AB - OBJECTIVE: The aim of this study was to primarily investigate the usefulness of computerized tomographic (CT) fistulography in the diagnosis and management of branchial cleft fistulae and sinuses. STUDY DESIGN: Fifteen patients with confirmed branchial fistulae or sinuses who had undergone CT fistulography were included. The diagnoses were confirmed by clinical, radiologic, or histopathologic examinations. The internal openings, distribution, and neighboring relationship of the lesions presented by CT fistulography were analyzed to evaluate the usefulness in comparison with x-ray fistulography. RESULTS: Nine patients were diagnosed with first branchial fistulae or sinuses, 2 with second branchial fistulae, and 4 with third or fourth branchial fistulae. The presence and location of the lesions could be seen on x-ray fistulography. The distribution of the lesions, internal openings, and neighboring relationship with parotid gland, carotid sheath, and submandibular gland could be clearly demonstrated on CT cross-sectional or volume-rendering images. CONCLUSIONS: CT fistulography could provide valuable information and benefit surgical planning by demonstrating the courses of branchial anomalies in detail. PMID- 22668629 TI - Mandibular cortical bone evaluation on cone beam computed tomography images of patients with bisphosphonate-related osteonecrosis of the jaw. AB - OBJECTIVES: The objective of this study was to develop a technique for detecting cortical bone dimensional changes in patients with bisphosphonate-related osteonecrosis of the jaw (BRONJ). STUDY DESIGN: Subjects with BRONJ who had cone beam computed tomography imaging were selected, with age- and gender-matched controls. Mandibular cortical bone measurements to detect bisphosphonate-related cortical bone changes were made inferior to mental foramen, in 3 different ways: within a fixed sized rectangle, in a rectangle varying with the cortical height, and a ratio between area and height. RESULTS: Twelve BRONJ cases and 66 controls were evaluated. The cortical bone measurements were significantly higher in cases than controls for all 3 techniques. The bone measurements were strongly associated with BRONJ case status (odds ratio 3.36-7.84). The inter-rater reliability coefficients were high for all techniques (0.71-0.90). CONCLUSIONS: Mandibular cortical bone measurement is a potentially useful tool in the detection of bone dimensional changes caused by bisphosphonates. PMID- 22668630 TI - Drug-related osteonecrosis of the jaws: "Exposure, or not exposure: that is the question". PMID- 22668631 TI - Clopidogrel-induced ageusia: a possible overlooked etiology by dentists? PMID- 22668632 TI - Cervicofacial actinomycosis: most common or second most common type of actinomycosis? PMID- 22668635 TI - Posttransplant lymphoproliferative disorder presenting as a nonhealing extraction socket: a case report and review of the literature. AB - Posttransplant lymphoproliferative disorder (PTLD) is a well-recognized complication of long-term immunosuppression following hematopoietic or solid organ transplantation and is associated with significant morbidity and mortality. We present a unique case of PTLD that manifested with a nonhealing dental extraction socket 17 years after renal transplantation. We summarize the existing literature and present a review of an additional 25 cases. These highlight the variable clinical presentations of PTLD within the oral cavity and clear potential for delayed presentation at this anatomical subsite. PMID- 22668636 TI - Acute gingival bleeding as a complication of falciparum malaria: a case report. AB - INTRODUCTION: Acute gingival bleeding can occasionally be the only sign of systemic bleeding problems. The diagnosis and management of such conditions may challenge the skills of the dentist. CASE REPORT: The present report describes a case of severe, prolonged gingival bleeding in a 54-year-old woman as a consequence of Plasmodium falciparum malaria infection. Specific highlights are focused on the management of the patient with emphasis on early diagnosis of the disease so as to improve the prognosis. This case report also stresses that medical intervention to correct the underlying aberration of hemostasis is necessary for local dental measures to successfully stop bleeding. CONCLUSIONS: Acute gingival bleeding as a complication of systemic disease can be challenging to manage unless the underlying systemic cause is diagnosed. Therefore, the dentist must be aware of various systemic conditions that can lead to gingival bleeding. The present case report describes a patient with acute gingival bleeding secondary to Plasmodium falciparum infection. PMID- 22668637 TI - Non-Hodgkin lymphoma involving the mandible: imaging findings. AB - OBJECTIVE: The aim of this study was to investigate the imaging findings of non Hodgkin lymphoma (NHL) involving the mandible. STUDY DESIGN: The imaging studies of 4 patients with NHL involving the mandible were retrospectively reviewed. Panoramic and computerized tomographic (CT) images were available for all patients. Magnetic resonance imaging (MRI) was available for 3 patients. RESULTS: On panoramic images, an apparent radiolucent lesion was found in only 2 of 4 cases. However, in all cases careful observation demonstrated imaging findings suggesting malignancy. On CT and MRI, tumor replaced the bone marrow in all cases and spread to the surrounding soft tissue in 3 cases. Cortical bone destruction tended to be mild for the extent of tumor involvement. CONCLUSIONS: NHL involving the mandible tended to show slight or mild cortical bone destruction relative to the extent of the tumor involvement. Careful observation was considered to be necessary when interpreting conventional images, because they might not clearly demonstrate bone destruction. PMID- 22668638 TI - Evaluation of interproximal caries using the IPad 2 and a liquid crystal display monitor. AB - OBJECTIVE: The objective of this study was to compare the detection of interproximal caries in digital intraoral images presented in a 24-inch liquid crystal display (LCD) monitor and the IPad 2. STUDY DESIGN: Twenty-seven digital bitewing radiographs of 102 adult teeth were generated by a charge-coupled device sensor and presented to 4 dentists in 2 sessions. The dentists were asked to rate the presence or absence of carious lesions using a 5-point scale. Differences in sensitivity, specificity, and accuracy were weighted using the Wilcoxon test, and the z test for the receiver operating characteristic curves. RESULTS: For the IPad 2 and LCD monitor, A(z) values were 0.87 and 0.86, respectively. For the tablet, the mean values of sensitivity, specificity, and accuracy were 0.75, 0.86, and 0.83, respectively. For the LCD monitor, these values were 0.77, 0.82, and 0.80, respectively. PMID- 22668640 TI - Minimization of hepatitis B infection by a 25-year universal vaccination program. AB - BACKGROUND & AIMS: Hepatitis B virus (HBV) infection was hyperendemic in Taiwan before the implementation of the universal infant hepatitis B immunization program, which was launched in 1984. Five previous seroepidemiologic surveys were conducted at 0, 5, 10, 15, and 20 years after the launch of the vaccination program. METHODS: We enrolled 3332 subjects younger than 30 years of age, with approximately 100 of them in each age cohort. Subjects were recruited voluntarily from schools and other institutions in Taipei, as in previous surveys. HBV seromarkers included hepatitis B surface antigen (HBsAg) and antibodies to HBsAg (anti-HBs) and hepatitis B core antigen (anti-HBc). HBV DNA levels were measured in anti-HBc positive/HBsAg negative subjects (anti-HBc only). RESULTS: The HBsAg, anti-HBs, and anti-HBc seropositive rates were very different between subjects born after the program in 2009 and the baseline group in 1984 (0.9% vs. 10%, 55.9% vs. 24.5%, and 7.0% vs. 28%, respectively). In this 6th survey, we showed that HBsAg prevalence further decreased in the vaccinated cohorts. A positive maternal HBsAg status was found in 86% of vaccine failures. Serum HBV DNA was detected in 4.2% (6/142) of anti-HBc positive/HBsAg negative subjects, with a low level of HBV DNA. All of these six subjects' HBV were genotype C. CONCLUSIONS: The universal infant HBV immunization program in Taiwan has completed its 25-year follow-up and its efficacy in young adults is clear. The continued decrease in HBsAg prevalence suggests that the elimination of HBV infection is becoming a reality. PMID- 22668639 TI - Critical role of cytochrome P450 2E1 (CYP2E1) in the development of high fat induced non-alcoholic steatohepatitis. AB - BACKGROUND & AIMS: Ethanol-inducible cytochrome P450 2E1 (CYP2E1) activity contributes to oxidative stress. However, CYP2E1 may have an important role in the pathogenesis of high-fat mediated non-alcoholic steatohepatitis (NASH). Thus, the role of CYP2E1 in high-fat mediated NASH development was evaluated. METHODS: Male wild type (WT) and Cyp2e1-null mice were fed a low-fat diet (LFD, 10% energy derived) or a high-fat diet (HFD, 60% energy-derived) for 10 weeks. Liver histology and tissue homogenates were examined for various parameters of oxidative stress and inflammation. RESULTS: Liver histology showed that only WT mice fed a HFD developed NASH despite the presence of increased steatosis in both WT and Cyp2e1-null mice fed HFD. Markers of oxidative stress such as elevated CYP2E1 activity and protein amounts, lipid peroxidation, protein carbonylation, nitration, and glycation with increased phospho-JNK were all markedly elevated only in the livers of HFD-fed WT mice. Furthermore, while the levels of inflammation markers osteopontin and F4/80 were higher in HFD-fed WT mice, TNFalpha and MCP-1 levels were lower compared to the corresponding LFD-fed WT. Finally, only HFD-fed WT mice exhibited increased insulin resistance and impaired glucose tolerance. CONCLUSIONS: These data suggest that CYP2E1 is critically important in NASH development by promoting oxidative/nitrosative stress, protein modifications, inflammation, and insulin resistance. PMID- 22668641 TI - A population-based study of the epidemiology of hepatitis C in a North American population. AB - BACKGROUND & AIMS: Chronic hepatitis C virus (HCV) infection is a major public health problem with approximately 3% of the world's population thought to be chronically infected. However, population-based data regarding HCV incidence rates, prevalence, residence, age, and gender distributions within North America are limited. We aimed at providing a detailed descriptive epidemiology of HCV infection in a North American population with a focus on time trends in incidence rates and prevalence of newly diagnosed HCV infection since 1991, the time when laboratory testing for HCV infections became first available. METHODS: A Research Database was developed linking records from multiple administrative sources. HCV positive residents of the Canadian province of Manitoba were identified during a twelve-year period (1991-2002). The cumulative and annual incidence rates and the prevalence of newly diagnosed HCV infection in Manitoba were examined and compared between different demographic groups and urban vs. rural residents. RESULTS: A total of 5018 HCV positive cases were identified over a 12-year period. The annual number of newly diagnosed HCV infections peaked in 1998 (59.2/100,000). On the other hand, the known prevalence of HCV continued to increase (4.6-fold during the 12-year study period) among both men and women reflecting the chronic nature of the disease. Males were 1.7 times more often infected than females. HCV infections were more common in urban centers. CONCLUSIONS: Between 1995 and 2002, there was a fairly constant trend for newly diagnosed HCV infection, ranging from approximately 500 to 600 new cases annually. Hence, with a stable population size, and a low case fatality rate, the prevalence of HCV infected persons in our population has been steadily rising. There is no evidence to suggest that the incidence of HCV infection will raise, however, the burden of chronic HCV infection will continue to increase, particularly amongst older males and those residing in urban centers. PMID- 22668642 TI - How transient becomes stable: an epigenetic switch linking liver inflammation and tumorigenesis. PMID- 22668643 TI - [It is difficult to establish evidence-based clinical behavior]. PMID- 22668644 TI - [Challenges and solutions in global health]. PMID- 22668645 TI - [Primary health care contributes to global health]. AB - Global health interventions often focus on specific diseases, thus forming vertical programmes. Studies show that vertical programmes perform poorly, which underlines the need for a horizontal basis: universal community-based primary health care, which improves health equity and outcomes. The diagonal approach supports an integrated patient-centered health-care system. The ''15% by 2015'' initiative suggests that vertical programmes invest 15% of their budgets in strengthening integrated primary health care. Strategies depend on local context. PMID- 22668646 TI - [Solutions to the global shortage of health workers]. AB - The global shortage of health workers in a world with interdependence and vast inequalities in health calls for internationally coordinated context-sensitive actions to build a global health workforce of sufficient quantity and quality. This status article describes the global crisis in the health workforce and some solutions and stakeholders in play. PMID- 22668647 TI - [Rickettsiosis should be considered as a differential diagnosis in patients having fever related to travelling]. AB - Rickettsial diseases are increasingly reported in international travellers. Prospective studies have shown that 2-4 % of travellers returning with fever have a rickettsiosis. We discuss epidemiology, clinical findings, diagnostics, treatment and prevention of rickettsiosis. In conclusion, rickettsiosis should be considered in the returned traveller with fever, especially when malaria, dengue fever and typhoid fever have been excluded. There is a possibility that doxycycline may have a prophylactic effect on rickettsiosis, but this thesis is only imaginary and needs further investigation. PMID- 22668648 TI - [Rickettsiosis is a neglected cause of fever in returned travellers]. AB - We present two cases of rickettsial infections in travellers caused by Rickettsia typhi and R. africae respectively. The two cases illustrate the widely varying symptomatology and aetiology. Incidence and treatment of the disease are discussed. The diagnosis is complex, and we believe that rickettsiosis is an underestimated cause of fever in returned travellers from the tropics. In the past two years only 26 cases have been diagnosed in Denmark. Whenever rickettsiosis is clinically suspected, empiric treatment with doxycycline should be initiated. PMID- 22668649 TI - [Lemierre's syndrome as differential diagnosis of lung cancer]. AB - Lemierre's syndrome is a disseminated infection which is usually caused by Fusobacterium necrophorum. An oropharyngeal infection progresses to a septic thrombophlebitis of the internal jugular vein and later metastatic infections throughout the body occur. We present a clinical case in which a patient, initially presenting with symptoms characteristic of pulmonary cancer, turned out to have a rare variant of Lemierre's syndrome caused by Fusobacterium nucleatum. PMID- 22668650 TI - [Lemierre's syndrome following peritonsillar abscess]. AB - Lemierre's syndrome is a rare but serious condition, characterized by disseminated infection with Fusobacterium necrophorum, most often originating from the oropharynx. Thrombophlebitis of the internal jugular vein and septic embolisms to various organs is the typical clinical picture. We describe a 16 year-old man with peritonsillar abscess who developed abscesses in lungs, liver and spleen. The patient was admitted to the ICU and treated with surgical drainage of infectious foci, antibiotics and anticoagulant therapy. After six weeks of antibiotic treatment the patient was discharged with no sequelae. PMID- 22668651 TI - [Tracheomalacia as a cause of chronic cough]. AB - Tracheomalacia is a rare condition involving increased flaccidity of the tracheal cartilage, widening of the posterior membranous wall and a reduced airway calibre. This combination can cause a tracheal collapse, expiratory flow obstruction and decreased clearance of secretions. We present a case of a 70-year old woman with severe coughing symptoms and obvious tracheomalacia diagnosed with a high resolution computed tomography in the expiratory phase. On a computed tomography, tracheomalacia has an easily recognizable pattern, which is only visible during expiration. Tracheomalacia is probably an underdiagnosed condition. PMID- 22668652 TI - [Significant effect of IL-1 receptor antagonist treatment in two patients who had CINCA syndrome with constant symptoms for 13 years]. AB - We report two cases of chronic infantile neurological, cutaneous, and articular (CINCA) syndrome. It is a rare congenital multisystemic inflammatory disease characterised by early onset of urticarial skin rash, central nervous system involvement and articular signs. Our two cases were first diagnosed at 13 and 14 years of age, respectively. From birth they presented with typical symptoms of CINCA syndrome, however isolated each symptom was non-specific. After the syndrome was recognised and treatment with anakinra was initiated, most symptoms disappeared. PMID- 22668653 TI - [Severe phimosis as cause of urosepsis with Actinobaculum schaalii]. AB - Actinobaculum schaalii is a small, Gram-positive, facultative anaerobic, CO2 requiring rod. It is now an acknowledged uropathogen, but often overlooked because of its slow growth. It is part of the normal bacterial flora in the urogenital area, but can be the cause of both local and invasive infections. We present a case of A. schaalii urosepsis in a 68-year-old male with phimosis caused by a severe lichen sclerosus et atrophicus. The only bacteria found in blood and urine was A. schaalii. PMID- 22668654 TI - [Bilateral adrenal haemorrhage during sepsis does not equal total adrenal insufficiency]. AB - Bilateral adrenal haemorrhage can occur in the setting of severe clinical sepsis. The clinical presentation may be non-specific, and the degree to which adrenal haemorrhage causes adrenal insufficiency remains unclear. We describe a case of an 18-year-old male presenting with meningococcaemia. The diagnosis was confirmed by a computed tomography, and the patient was treated with antibiotics and corticosteroids. His adrenal function was initially subnormal; however, three months after discharge, he had fully recovered his adrenal function. PMID- 22668656 TI - Distribution of nonapeptide systems in the forebrain of an African cichlid fish, Astatotilapia burtoni. AB - Nonapeptides and their receptors have important functions in mediating social behavior across vertebrates. Where these nonapeptides are synthesized in the brain has been studied extensively in most vertebrate lineages, yet we know relatively little about the neural distribution of nonapeptide receptors outside of mammals. As nonapeptides play influential roles in behavioral regulation in all vertebrates, including teleost fish, we mapped the distributions of the receptors for arginine vasotocin (AVT; homolog of arginine vasopressin) and isotocin (IST; homolog of oxytocin/mesotocin) throughout the forebrain of Astatotilapia burtoni, an African cichlid fish with behavioral phenotypes that are plastic and reversible based on the immediate social environment. We characterized the distribution of the AVT V1a2 receptor (V1aR) and the IST receptor (ITR) using both immunohistochemistry for protein detection and in situ hybridization for mRNA detection, as well as AVT and IST using immunohistochemistry. Expression of the neuropeptide receptors was widely distributed throughout the fore- and midbrain, including the proposed teleost homologs of the mammalian amygdala complex, striatum, hypothalamus, and ventral tegmental area. We conclude that although the location of nonapeptide synthesis is restricted compared to tetrapod vertebrates, the distribution of nonapeptide receptors is highly conserved across taxa. Our results significantly extend our knowledge of where nonapeptides act in the brains of teleosts to mediate social transitions and behavior. PMID- 22668657 TI - Magnesium deficiency: does it have a role to play in cataractogenesis? AB - Magnesium is one of the most important regulatory cation involved in several biological processes. It is important for maintaining the structural and functional integrity of vital ocular tissues such as lens. Presence of high magnesium content especially in the peripheral part of lens as compared to aqueous and vitreous humor has been observed. Magnesium plays significant role as a cofactor for more than 350 enzymes in the body especially those utilizing ATP. Membrane associated ATPase functions that are crucial in regulating the intracellular ionic environment, are magnesium-dependent. Moreover, the enzymes involved in ATP production and hydrolysis are also magnesium-dependent. Magnesium deficiency by interfering with ATPase functions causes increased intracellular calcium and sodium and decreases intracellular potassium concentration. Furthermore, magnesium deficiency is associated with increased oxidative stress secondary to increased expression of inducible nitric oxide synthase and increased production of nitric oxide. Thus the alterations in lenticular redox status and ionic imbalances form the basis of the association of magnesium deficiency with cataract. In this paper we review the mechanisms involved in magnesium homeostasis and the role of magnesium deficiency in the pathogenesis of cataract. PMID- 22668659 TI - Troponin I: how high is too high? AB - Elevated cardiac troponin I can occur in patients with cardiac injury or sepsis. However, extreme elevations of serum cardiac troponin I in pediatric patients without myocardial injury are rare. We present a case of a 14-year-old girl involved in a motor vehicle accident with muscle injury, who was readmitted with sepsis and severely elevated serum cardiac troponin I level in the absence of myocardial injury. PMID- 22668660 TI - Unusual cause of abdominal pain in pediatric emergency medicine. AB - Atypical manifestations of acute hepatitis A virus (HAV) infection include ascites, pleural effusion, acute renal failure, aplastic anemia, and neurological manifestations. Although association of HAV and acute cholecystitis is known, presentation of hepatitis A infection with acute cholecystitis has not been reported in pediatric emergency medicine literature. Primary acute acalculous cholecystitis in children is rare and commonly attributed to systemic infections. We report a case of a child developing acute viral cholecystitis as a presenting feature of sporadic HAV infection and review HAV-associated cholecystitis in children. The article provides a brief illustration of evaluating acute abdominal pain in older children in the emergency department in a developing country. PMID- 22668661 TI - "Magnetic attraction" in the pediatric emergency department: the case of a malfunctioning implantable cardioverter-defibrillator. AB - The use of implantable cardioverter-defibrillators (ICDs) in pediatric patients has increased substantially over the past 3 decades. We report the case of a 15 year-old boy with congenital heart disease who presented with recurrent inappropriate ICD shocks due to a lead malfunction. Inaccessibility of a magnet to inactivate shock therapy in the pediatric emergency department (PED) resulted in numerous additional inappropriate shocks. Herein, we provide a brief overview of ICD care relevant to the PED. The complexities of these devices and their associated therapies require pediatric emergency physicians caring for these patients to recognize basic ICD functions and troubleshoot malfunctions to provide timely management. In particular, it is essential that PEDs be equipped with magnets and that physicians are trained in their appropriate use. PMID- 22668662 TI - Intracardiac thrombus case caused by blunt trauma due to child abuse. AB - Intracardiac thrombus is a rare condition in children, although there has recently been an increase in case reports in the literature. We here report an asymptomatic intracardiac thrombus caused by blunt trauma due to child abuse in a 4-year-old girl. On the echocardiogram, one can see pericardial fluid surrounding all of the heart, and a mobile mass, a thrombus of 5.8 * 9 mm in diameter, was observed in the right atrium and on the free border of the tricuspid valve. The thrombus and pericardial fluid disappeared on the follow-up echocardiogram performed after the 10-day heparin therapy. PMID- 22668663 TI - Bilateral acetabular fractures in an adolescent after low-energy trauma. AB - BACKGROUND: Pediatric pelvic fractures are rare, accounting for approximately 2.4% to 5.5% of annual admissions at large level I trauma centers. An acetabular fracture is involved in only about 1% to 15% of these cases and is almost exclusively caused by a high-energy trauma. METHODS: This is a report of an otherwise healthy 15-year-old male adolescent who sustained a nondisplaced bilateral anterior column and wall acetabular fracture after a low-energy mechanism during a hockey game. The patient was managed nonoperatively with non weight-bearing restrictions and had complete resolution of his symptoms by 10 weeks. RESULTS: This case shows that a low-energy mechanism can create significant bilateral acetabular fractures in the immature skeleton. CONCLUSIONS: The presented case may represent an underdiagnosed cause of hip and groin pain in the adolescent patient/athlete when initial radiographs appear normal. PMID- 22668664 TI - Acute ulnar nerve entrapment after closed reduction of a posterior fracture dislocation of the elbow: a case report. AB - We present the case of a child who had a posterior-lateral elbow dislocation with an intact ulnar nerve documented before an attempted reduction, with subsequent loss of ulnar nerve function after the elbow was reduced.Dislocations of the elbow in children represent only 3% to 6% of all elbow injuries. Posterior elbow dislocations are the most common, with more than one half involving an associated fracture about the elbow. The most common associated fracture is the medial epicondyle. Even though it is known that injury to the ulnar nerve can occur in elbow dislocations, we found only 1 other case report describing intra-articular entrapment of the ulnar nerve after an elbow dislocation.This case demonstrates several important clinical issues. First, it highlights the potential risk of ulnar nerve entrapment after closed reduction of elbow dislocations in children. Second, it confirms the importance of careful prereduction and postreduction examinations in the pediatric patient presenting with a dislocated elbow. PMID- 22668665 TI - Pediatric blast lung injury from a fireworks-related explosion. AB - Blast injuries related to explosions have been described in the literature but are uncommon in children. We describe a multisystem blast injury in a child resulting from a commercial firework-related explosion in her home. She presented with respiratory failure, shock, altered level of consciousness, and multiple orthopedic injuries. The patient required immediate stabilization and resuscitation in the emergency department and a prolonged hospitalization. This report reviews the spectrum of injuries that are seen in blast-related trauma and the emergency measures needed for rapid stabilization of these critical patients. PMID- 22668666 TI - Pediatric emergency medicine: legal briefs. PMID- 22668667 TI - A hypertensive child with irritability and a rash. PMID- 22668668 TI - Acute sexual assault: a review. AB - Acute sexual assault includes a broad spectrum of nonconsensual sexual activity. Care of victims of acute sexual assault can be challenging, especially given the significant potential psychological and legal ramifications of the event and subsequent medical care and forensic evidence collection. In some emergency department settings, utilization of sexual assault response teams and sexual assault nurse examiners has demonstrated that a systematic approach to these patients improves care. However, given that victims of acute sexual assault are likely to present for care in emergency departments where such teams do not exist, it is critical for the emergency medicine physician, pediatrician, and family physician to have knowledge of key aspects of history taking, the physical examination, evidence collection, and medical record documentation. This review of care of the victim of acute sexual assault will provide practitioners with the tools needed to effectively evaluate these patients. PMID- 22668669 TI - ECGs in the ED. PMID- 22668670 TI - Domestic animals as a warning sign for carbon monoxide poisoning. PMID- 22668671 TI - Ondansetron-associated hypotension following pediatric self-poisoning. PMID- 22668673 TI - A systematic review of screening questionnaires for childhood lead poisoning. AB - CONTEXT: The Centers for Disease Control and Prevention encourages the use of risk factor questionnaires to screen children for lead poisoning. A majority of state health departments have formal lead screening guidelines that recommend health care providers use questionnaires. OBJECTIVE: We conducted a systematic review to evaluate the ability of lead screening questionnaires to predict lead poisoning risk among children. METHODS: Articles that reported the evaluation of a predesigned lead screening questionnaire were obtained by searching Medline/PubMed and by examining references of articles obtained through the online search. From each evaluation, we abstracted the number of children that were true positive, false positive, true negative, and false negative, according to the results of the screening questionnaire and the follow-up blood lead test. From these data, we calculated specificity and sensitivity of the questionnaire for each evaluation. RESULTS: Twenty articles met the inclusion criteria: these included 28 separate questionnaire evaluations. Among 17 evaluations of the 1991 Centers for Disease Control and Prevention questionnaire, sensitivity ranged from 0.25 to 0.87, specificity from 0.31 to 0.80, and accuracy (sum of sensitivity and specificity) from 0.74 to 1.39. The pooled mean estimates for this questionnaire were sensitivity 0.61 (95% confidence interval: 0.53-0.68); specificity 0.52 (0.45-0.60); accuracy 1.12 (1.06-1.18). Among 11 evaluations of all other questionnaires, sensitivity ranged from 0.43 to 0.90, specificity from 0.17 to 0.66, and accuracy from 0.94 to 1.27. For these questionnaires, the pooled mean estimates were sensitivity 0.76 (0.68-0.85), specificity 0.41 (0.33-0.49), and accuracy 1.12 (1.06-1.18). CONCLUSIONS: Lead screening questionnaires showed a wide range of sensitivity and specificity and performed little better than chance at predicting lead poisoning risk among children. PMID- 22668674 TI - Fatty acid profile and proliferation of bovine blood mononuclear cells after conjugated linoleic acid supplementation. AB - BACKGROUND: Conjugated linoleic acids (CLA) are in focus of dairy cattle research because of its milk fat reducing effects. Little is known about the impact of CLA on immune function in dairy cows. Therefore, in the present study we investigated the effects of a long term supplementation of dairy cows with CLA on the fatty acid profile of peripheral blood mononuclear cells (PBMC) and their proliferation ex vivo. RESULTS: The supplementation of dairy cows with either 100 g/d of a control fat preparation (CON, n = 15), 50 g/d of the control fat preparation and 50 g/d CLA supplement - containing 12.0% cis-9, trans-11 and 11.9% trans-10, cis 12 CLA of total fatty acid methyl esters - (CLA-50, n = 15) or 100 g/d of the CLA supplement (CLA-100, n = 16) did not influence the major fatty acids (C18:0, C16:0, cis-9 C18:1, cis-9, cis-12 C18:2, cis-5, cis-8, cis-11, cis-14 C20:4) in the lipid fraction of PBMC. The proportion of trans-10, cis-12 CLA of total fatty acids was increased in both CLA supplemented groups, but there was no effect on the cis-9, trans-11 isomer. Furthermore, the proportion of trans-9 C18:1 and cis 12 C24:1 was reduced in the CLA-100 group. The mitogen stimulated cell proliferation was not influenced by CLA feeding. CONCLUSION: CLA supplementation influenced the FA profile of some minor FA in PBMC, but these changes did not lead to differences in the mitogen induced activation of the cells. PMID- 22668675 TI - Meaningful task-specific training (MTST) for stroke rehabilitation: a randomized controlled trial. AB - BACKGROUND/OBJECTIVE: The upper extremity motor deficit is one of the functional challenges in post stroke patients. The objective of the present study was to evaluate the effectiveness of the meaningful task-specific training (MTST) on the upper extremity motor recovery during the subacute phase after a stroke. METHOD: This was a randomized, controlled, double-blinded trial in the neurology department of a university hospital and occupational therapy unit of a rehabilitation institute. A convenience sample of 103 people, 4 to 24 weeks (mean, 12.15 weeks) after the stroke, was randomized into 2 groups (MTST, 51; standard training group, 52). Subjects in the Brunnstrom stage of arm recovery of 2 to 5 were included in the study. Ninety-five participants completed the 8-week follow-up. INTERVENTIONS: Participants were assigned to receive either the MTST or dose-matched standard training program based on the Brunnstrom stage and Bobath neurodevelopmental technique, 4 to 5 days a week for 4 weeks. Fugl-Meyer assessment (FMA), Action Research Arm Test (ARAT), Graded Wolf Motor Function Test (GWMFT), and Motor Activity Log (MAL) were outcome measures RESULTS: The MTST group showed a positive improvement in the mean scores on the outcome measures at post and follow-up assessments in comparison to the control group. Further, statistically significant differences were observed in changes between the groups at post and follow-up assessment for FMA, ARAT, GWMFT, and MAL. CONCLUSION: The MTST produced statistically significant and clinically relevant improvements in the upper extremity motor recovery of the patients who had a subacute stroke. PMID- 22668676 TI - Transfer effects of training-induced visual field recovery in patients with chronic stroke. AB - OBJECTIVE: Visual training of light detection in the transition zone between blind and healthy hemianopic visual fields leads to improvement of color and simple pattern recognition. Recently, we demonstrated that visual field enlargement (VFE) also occurs when an area just beyond the transition zone is stimulated. In the current study, we attempted to determine whether this peripheral training also causes improvement in color and shape perception and reading speed. Further, we evaluated which measure of VFE relates best to improvements in performance: the average border shift (ABS) in degrees or the estimated amount of cortical surface gain (ECSG) in millimeters, using the cortical magnification factor (CMF). METHOD: Twelve patients received 40 sessions of 1-hour restorative function training (RFT). Before and after training, we measured visual fields and reading speed. Additionally, color and shape perception in the trained visual field area was measured in 7 patients. RESULTS: VFE was found for 9 of 12 patients. Significant improvements were observed in reading speed for 8 of 12 patients and in color and shape perception for 3 of 7 patients. ECSG correlates significantly with performance; ABS does not. Our data indicate that the threshold ECSG, needed for significant changes in color and shape perception and reading speed, is about 6 mm. CONCLUSIONS: White stimulus training-induced VFE can lead to improved color and shape perception and to increased reading speed in and beyond the pretraining transition zone if ECSG is sufficiently large. The latter depends on the eccentricity of the VFE. PMID- 22668677 TI - Acupuncture for stroke: evidence of effectiveness, safety, and cost from systematic reviews. AB - OBJECTIVE: To provide an overview of evidence from systematic reviews and meta analysis on the effectiveness, safety, and cost of acupuncture for stroke. METHODS: Two authors selected the articles according to inclusion and exclusion criteria, and 2 authors extracted data from the reviews. Potentially relevant systematic reviews were searched through the Cochrane Library, MEDLINE, EMBASE, AMED, CISCOM, Chinese Biological Medicine Database (CBMD), Chinese Scientific Journal Database (VIP), Chinese periodicals in the China National Knowledge Infrastructure (CNKI), and Chinese Evidence-Based Medicine Database. The evidence was based on the reviews and meta-analysis. RESULTS: Nine articles were indentified: 1 focused on acute stroke; 1 focused on subacute or chronic stroke; 5 focused on stroke (the interval after stroke onset was variable in these studies); and 2 addressed dysphagia after stroke. There is a split among reviewers regarding the effectiveness of acupuncture for stroke recovery. The most reliable evidence showed that there was no clear benefit of acupuncture for stroke patients in acute, subacute, or chronic stages. There was not a single economic analysis of acupuncture for treatment of stroke. CONCLUSIONS: Acupuncture treatment seems to be relatively safe. The evidence for the effectiveness of acupuncture for stroke was inconclusive, mainly due to poor methodological quality and small samples. For future research, further high quality, randomized controlled trials with long-term follow-up are needed, as well as economic analysis. PMID- 22668678 TI - Effects of Mendelsohn maneuver on measures of swallowing duration post stroke. AB - PURPOSE: The purpose of this pilot study was to determine whether intensive use of the Mendelsohn maneuver in patients post stroke could alter swallow physiology when used as a rehabilitative exercise. METHOD: Eighteen outpatients between 6 weeks and 22 months post stroke were enrolled in this prospective study using a crossover design to compare 2 weeks of treatment with 2 weeks of no treatment. Each participant received an initial videofluoroscopic swallow study (VFSS) and an additional VFSS at the end of each week for 1 month for a total of 5 studies. During treatment weeks, participants received 2 treatment sessions per day performing Mendelsohn maneuvers with surface electromyography for biofeedback. Measures of swallowing duration, penetration/aspiration, residue, and dysphagia severity were analyzed from VFSS to compare treatment and no-treatment weeks. RESULTS: Significant changes occurred for measures of the duration of superior and anterior hyoid movement after 2 weeks of treatment. Improvements were observed for duration of opening of the upper esophageal sphincter (UES), but results were not statistically significant. Measures of penetration/aspiration, residue, and dysphagia severity improved throughout the study, but no differences were observed between treatment and no-treatment weeks. CONCLUSIONS: Intensive use of the Mendselsohn maneuver in isolation altered duration of hyoid movement and UES opening in this exploratory study. Results can guide future research toward improved selection criteria and exploration of outcomes. Larger numbers of participants and variations in treatment duration and intensity will be necessary to determine the true clinical value of this treatment. PMID- 22668679 TI - Occupational gaps in everyday life one year after stroke and the association with life satisfaction and impact of stroke. AB - PURPOSE: To examine the presence, frequency, and distribution of occupational gaps and to explore whether there are associations between occupational gaps and life satisfaction, self-rated recovery, and functioning and participation in activities of daily living (ADLs) 1 year after stroke. METHOD: Data were collected at onset and at 12 months after stroke from 161 patients admitted to a stroke unit in central Sweden by using Occupational Gaps Questionnaire, LiSat-11, Stroke Impact Scale, Katz ADL Index, and Barthel Index. Spearman rank correlation and Mann Whitney U test were used in the analyses. RESULTS: Occupational gaps were reported by 87% of the participants. The number of occupational gaps was moderately associated with participation and self-rated recovery. There was a significant difference in the number of occupational gaps between the participants who were independent in ADLs and those who were not, both at baseline and at 12 months after stroke. There was, however, no significant association between occupational gaps and life satisfaction. CONCLUSIONS: Occupational gaps 1 year after stroke are very common, particularly among individuals experiencing difficulties in ADLs. Increased efforts are vital to enable individuals to do the activities that are important to them, irrespective of whether these are instrumental ADLs or leisure or social activities. Occupational gaps could be reduced by developing rehabilitation interventions that enable desired activities in different contexts that are crucial for individual patients. PMID- 22668680 TI - A questionnaire to assess carers' experience of stroke rehabilitation. AB - PURPOSE: To establish the validity and reliability of a questionnaire measuring the experience of informal carers of patients with stroke through acute and rehabilitation hospital treatment. METHOD: The settings were 6 stroke units in the United Kingdom. Participants were relatives of patients with stroke. The Stroke Carer Experience Questionnaire (SCEQ) asks about specific elements of care and was constructed using qualitative analyses. Convergent and discriminant validity were assessed by correlations with other questionnaires and variables. Criterion validity was examined by correlations with indices derived from qualitative data. Temporal stability was assessed by correlation with a repeated administration. The performance of the questionnaire was compared with that of the Carer Hospital Satisfaction Questionnaire (Carer HospSat). RESULTS: Seventy two (49%) of 147 questionnaires were returned. Test-retest reliability, assessed by a questionnaire mailed 7 days after the first completion, was 0.77. The correlation with the Carer HospSat was 0.57, indicating convergent validity. The SCEQ did not correlate with demographic variables or functional ability, which indicated discriminant validity. Significant correlations with indices derived from carers' qualitative descriptions evidenced criterion validity. The SCEQ detected specific negative experiences among carers with high global satisfaction scores on the Carer HospSat. In general, the SCEQ items were not strongly intercorrelated; only 6% of the intercorrelations were strong to moderate (30.6). CONCLUSIONS: The SCEQ is preferable to existing questionnaires for carers of patients with stroke, because it has established validity and reliability and assesses service characteristics important to carers. It also identifies experiences in services that elude global satisfaction ratings. It is a promising instrument for identifying service strengths and unmet needs. PMID- 22668681 TI - Opinions of constraint-induced movement therapy among therapists in southwestern Ohio. AB - OBJECTIVE: To determine the opinions of therapists about constraint-induced movement therapy (CIMT). METHOD: A convenience sample of 92 therapists with at least 1 year of clinical experience working in outpatient and inpatient hospital and clinical neurorehabilitation settings was surveyed. Subjects completed a self report questionnaire discerning their opinions of CIMT during their clinical staff meetings. The questionnaire described CIMT to participants using excerpts from a recently published trial of CIMT. Subjects then responded to various statements concerning their opinions of the protocol and supplied the rationale for their opinions. RESULTS: Seventy-five percent of participants reported that it would be very difficult or difficult to administer CIMT in their clinics, and 83% felt that most clinics would not have the resources to implement CIMT. Additionally, more than 61% of respondents stated that managed care payers were either somewhat unlikely or very unlikely to reimburse for CIMT, and no respondent believed that it was very likely that managed care would fund CIMT. Most respondents felt that patients would experience great difficulty with the clinical session and restrictive device durations. There were 78.3% of participants who were not aware that an efficacious modified CIMT regimen was available that could overcome the aforementioned challenges. CONCLUSIONS: Findings were consistent with CIMT trials and surveys regarding client compliance difficulties and therapist misgivings. Findings argue for continued refinement of modified CIMT regimens as well as greater educational efforts regarding CIMT for therapists. PMID- 22668682 TI - Nursing practice and fatigue. PMID- 22668685 TI - A nurse-driven algorithm to screen for congenital heart defects in asymptomatic newborns. AB - Routine pulse oximetry screening (POS) performed on asymptomatic newborns after 24 hours of life, but before hospital discharge, may detect critical congenital heart defects (cCHD) when used as an adjunct to physical examination. Timely identification of this small percentage of newborns prompts early intervention and improves outcomes. New-generation, highly accurate pulse oximeters provide a simple, low-risk, low-cost tool to improve detection of potentially lethal cardiac lesions. The purpose of this study was to develop, implement, and test the utility of a nurse-driven algorithm that would support and serve as a guide for detection of cCHD in asymptomatic newborns using POS prior to discharge home from the hospital. Results showed that this collaborative protocol was easily implemented in a community hospital. The universal algorithm enhances POS and clinical examination to identify asymptomatic infants with undiagnosed cCHD prior to discharge from the hospital. PMID- 22668686 TI - Blood pressure support in the very low-birth-weight infant during the first week of life. AB - The immature cardiovascular system of very preterm infants predisposes them to low systemic blood flow during the first week of life, a state that may be damaging to multiple organ systems. There are many treatment strategies for the maintenance of cardiovascular equilibrium in these infants, each with its own advantages and risks. Caregivers are responsible for assessing the circulatory status of each patient and evaluating the effectiveness of interventions aimed at maintaining adequate systemic blood flow. Therefore, it is important to have an understanding of the mechanics of transitional circulation, the relationship between blood pressure and systemic blood flow, and the therapies used to treat infants with compromised organ perfusion. PMID- 22668688 TI - Congenital pulmonary lymphangiectasia: an unusual presentation of nonimmune hydrops in a preterm infant. AB - Congenital pulmonary lymphangiectasia (CPL) is a rare developmental disorder of the lung. CPL can present antenatally as nonimmune hydrops with pleural effusions, which are frequently associated with polyhydraminos. CPL presents in the neonatal period with severe respiratory distress and can be complicated by chylothorax. Diagnosis is difficult, as radiographic findings are nonspecific. Lung biopsy is indicated in some severe cases to diagnose CPL. The majority of infants with this condition rarely survive the neonatal period and are often diagnosed at autopsy. The final diagnosis is confirmed histologically by lung biopsy or at postmortem. We report a rare case of CPL in a preterm female infant presenting with severe nonimmune Hydrops fetalis who survived the neonatal period, and report clinical follow-up to early childhood. PMID- 22668689 TI - Positioning after feedings: what is the evidence to reduce feeding intolerances? AB - Nursing's goal is to be the least invasive as the patient's condition allows. As a NICU nurse, each feeding for our patients is a priority for them to grow and develop with the idea to speed discharge to home. When infants develop reflux or have increased gastric aspirates, we are concerned that their weight will taper and their length of stay will increase. Positioning provides nurses with a noninvasive option to care for these patients. The that the right-side position is best for infants to enhance digestion stems from theories of anatomy and physics. Research strengthens this supposition for those infants needing help with decreased gastric motility. Other research supports the left lateral and prone positions for those patients with GER. In practice, a patient does not necessarily have one or the other and in fact may have both GER and slowed gastric motility at any given time. The literature supports the right lateral position for enhancing gastric emptying or motility and left lateral position for GER in the uncomplicated patient with one gastrointestinal concern. The knowledge the research provides is encouraging to provide a solution, but it does not clarify the true issues of a complex patient who can have decreased gastric motility needing the right lateral position and also suffer from symptoms of GER requiring the left lateral position (see Table). For those more complicated infants, the solution might best be choosing the prone position. The prone position should not be forgotten as the findings of many studies, although not often the first choice (best results) showed it to be consistently the second best for digestive problems. In any case, the dominant positions appear to be the right or left lateral side with the prone position considered a reasonable compromise. Further research is needed to provide a clear choice for correct positioning in the NICU population. The reality for nurses is that neonatal patients are often fed every 3 hours and their lives depend on each feeding to provide nutrients for growth. It is ideal for these patients to receive every prescribed feeding and be comfortably placed in a variety of positions. Nurses' assumption that the right lateral position is best is considered, in most cases, to be a true statement for those infants with increased gastric aspirates. For those patients with GER, the left lateral position is more highly preferred. It is important for nurses to be aware of the literature but also guide their practice based on the patient assessment and presentation of symptoms. Future knowledge may provide nurses with the data needed to perfect positioning methods for infants with feeding intolerances. PMID- 22668690 TI - Neonatal nurse practitioner workforce survey executive summary. AB - The Neonatal Nurse Practitioner Workforce Survey, led by Paula Timoney, DNP, ARNP, NNP-BC, and Debra Sansoucie, EdD, RN, NNP-BC, with the National Association of Neonatal Nurse Practitioners (NANNP), provides data collected from more than 600 neonatal nurse practitioners to examine workforce characteristics and needs. NANNP commissioned the survey because no comprehensive data existed for the neonatal nurse practitioner workforce. The executive summary given in this article highlights some of the survey's key findings in the areas of demographics, practice environment, scope of responsibilities, and job satisfaction. Readers are encouraged to review the complete text of the Neonatal Nurse Practitioner Workforce Survey for more in-depth data and recommendations regarding NNP education, scope of practice, and scope of responsibility in the ever-changing health care environment. The report will be available for purchase at http://www.nannstore.org in summer 2012. PMID- 22668691 TI - A weight-based formula for the estimation of gastric tube insertion length in newborns. AB - OBJECTIVE: Safe and effective functioning of nasogastric and orogastric tubes in the neonatal intensive care unit (NICU) is achieved by ensuring their correct placement within the stomach. Insertion length has traditionally been estimated using morphological measures, but studies have indicated that these are frequently inaccurate. This study aimed to evaluate the frequency of correct tube placement and to determine a weight-based formula for estimation of insertion length. STUDY DESIGN: A prospective study was performed over a 6-month period in a tertiary NICU. Infants with gastric tubes who required radiography for clinical reasons were included. The infant's weight and the type and length of tube were documented. A radiologist assessed the tube position to be high, borderline, correct, or long. RESULTS: A total of 218 radiographs of infants weighing 397 to 4131 g were included. Correct tube position was achieved on 74% of occasions. By analyzing data for correct tube positions, formulas were derived to predict tube insertion length in centimeters: orogastric = [3 * weight (kg) + 12] and nasogastric = [3 * weight (kg) + 13]. The formulas correctly predicted 60% of misplaced orogastric tubes and 100% of misplaced nasogastric tubes. CONCLUSION: We propose a novel weight-based formula for estimation of gastric tube insertion length in newborn infants to improve the accuracy of this routine procedure. PMID- 22668692 TI - Parent's confidence as a caregiver. AB - PURPOSE: The purpose of this study was to describe the parent's self-reported confidence as a caregiver. The specific research questions were as follows: * What is the parent's perceived level of confidence when performing infant caregiving activities in the neonatal intensive care unit (NICU)? * What is the parent's projected level of confidence about performing infant caregiving activities on the first day at home? SUBJECTS: Participants were parents of infants with an anticipated discharge date within 5 days. Inclusion criteria were as follows: parent at least 18 years of age, infant's discharge destination is home with the parent, parent will have primary responsibility for the infant after discharge, and the infant's length of stay in the NICU was a minimum of 10 days. DESIGN/METHOD: Descriptive, survey research. MAIN OUTCOME MEASURES: Participants perceived themselves to be confident in all but 2 caregiving activities when caring for their infants in the NICU, but parents projected a change in their level of confidence in their ability to independently complete infant care activities at home. PRINCIPAL RESULTS: When comparing the self reported level of confidence in the NICU and the projected level of confidence at home, the levels of confidence decreased for 5 items, increased for 8 items, and remained unchanged for 2 items. All of the items with a decrease in score were the items with the lowest score when performed in the NICU. All of these low scoring items are caregiving activities that are unique to the post-NICU status of the infant. Interestingly, the parent's projected level of confidence increased for the 8 items focused on handling and interacting with the infant. CONCLUSIONS: The findings of this research provide evidence that nurses may need to rethink when parents become active participants in their infant's medical based caregiving activities. PMID- 22668693 TI - The impact of advanced practice nurses' shift length and fatigue on patient safety: position statement #3057. PMID- 22668694 TI - Proteolytic cleavage of the disease-related lysosomal membrane glycoprotein CLN7. AB - CLN7 is a polytopic lysosomal membrane glycoprotein of unknown function and is deficient in variant late infantile neuronal ceroid lipofuscinosis. Here we show that full-length CLN7 is proteolytically cleaved twice, once proximal to the used N-glycosylation sites in lumenal loop L9 and once distal to these sites. Cleavage occurs by cysteine proteases in acidic compartments and disruption of lysosomal targeting of CLN7 results in inhibition of proteolytic cleavage. The apparent molecular masses of the CLN7 fragments suggest that both cleavage sites are located within lumenal loop L9. The known disease-causing mutations, p.T294K and p.P412L, localized in lumenal loops L7 and L9, respectively, did not interfere with correct lysosomal targeting of CLN7 but enhanced its proteolytic cleavage in lysosomes. Incubation of cells with selective cysteine protease inhibitors and expression of CLN7 in gene-targeted mouse embryonic fibroblasts revealed that cathepsin L is required for one of the two proteolytic cleavage events. Our findings suggest that CLN7 is inactivated by proteolytic cleavage and that enhanced CLN7 proteolysis caused by missense mutations in selected luminal loops is associated with disease. PMID- 22668695 TI - Stimulating neuronal processes that benefit patients and our profession. PMID- 22668696 TI - MRI evaluation of movement of the mandibular condyle and articular disk on application of an occlusal splint. PMID- 22668699 TI - Stereolithographic cutting guide for fibula osteotomy. PMID- 22668700 TI - Use of the Beers criteria to identify potentially inappropriate drug use by community-dwelling older dental patients. AB - OBJECTIVE: Recognizing drugs with serious adverse experience (AE) potential in an aging population would assist practitioners in preventing drug safety issues. This study identifies drugs with potential for causing serious AEs, describes the AEs, and estimates prevalent use among older adults visiting the dentist. STUDY DESIGN: Drugs with serious AE risk for older adults were identified with the use of the Beers criteria. Analyses of older adults visiting the dentist using the Medicare Current Beneficiary Survey tested associations between demographic and health-related variables and use of these drugs. Potentially serious drug-related AEs are described. RESULTS: More than 3 in 10 older adults visiting the dentist were prescribed a Beers-criteria drug. Commonly prescribed Beers-criteria drugs used in dentistry include benzodiazepines and long-acting nonsteroidal antiinflammatory analgesics. CONCLUSIONS: Awareness of potentially harmful drug related AEs, their clinical consequences, and prescribing frequency for older adults will assist dentists in clinically managing patients and avoiding inappropriate prescribing. PMID- 22668701 TI - Tumor of the hard palate. PMID- 22668702 TI - Biosurfactants prevent in vitro Candida albicans biofilm formation on resins and silicon materials for prosthetic devices. AB - OBJECTIVE: The aim of this study was to evaluate in vitro the preventive antiadhesion activity of biosurfactants against Candida albicans biofilm. STUDY DESIGN: Disks of silicon and acrylic resin for denture prostheses were precoated with increasing concentrations of biosurfactants obtained from endophyte biofilms selected from Robinia pseudoacacia and from Nerium oleander, and afterward infected with C. albicans cells. The number of biofilm cells were detected by colony-forming unit (CFU) counting, cell viability was established by the 2,3 bis(2-methoxy-4-nitro-5-sulphophenyl)-5-[(phenyl amino)carbonyl]-2H-tetrazolium hydroxide (XTT) assay, and biosurfactant cytotoxicity was evaluated by the [3 (4,5-dimethyliazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphophenyl)-2H tetrazolium] (MTT) assay. Chlorhexidine was used as control. RESULTS: Precoating with biosurfactants caused a greater reduction (P < .01) in biofilm cell number and viability than chlorhexidine. The antiadhesion activity of the biosurfactants was observed at low concentrations (78.12 MUg/mL and 156.12 MUg/mL) which were noncytotoxic. CONCLUSIONS: This study demonstrated the preventive antiadhesion activity of biosurfactants against C. albicans biofilm. These agents are amphiphilic, interfere with microbial adhesion, and demonstrate cycompatibility with epithelial cells and fibroblasts. PMID- 22668703 TI - Clinical characteristics of lateral pterygoid myospasm: a retrospective study of 18 patients. AB - The available scientific literature on masticatory myospasm-induced oromandibular dystonia is limited. The objective of this study was to determine the clinical characteristics of lateral pterygoid myosapsm in a series of 18 patients. Clinical and electromyographic (EMG) data of 36 patients diagnosed with masticatory muscle myospasm were reviewed, and data from 18 patients with needle EMG-confirmed lateral pterygoid myospasm were extracted for retrospective study. The study population included 6 men and 12 women with a mean age of 53.2 +/- 15.3 years. Patients' chief complaints, severity and frequency of myospasm, clinical observations, video recordings, and surface/needle EMG recordings were analyzed. Despite the variety of manifestations, 3 characteristic signs and symptoms of lateral pterygoid myospasm were observed. These were: 1) jaw function disabilities; 2) difficulty in jaw closing after wide opening; and 3) involuntary jaw movements. A differential diagnosis of lateral pterygoid myospasm should be included when oromandibular dystonia is accompanied by the fore mentioned. PMID- 22668704 TI - Clinical and histologic healing of lichenoid oral lesions following amalgam removal: a prospective study. AB - OBJECTIVE: This study aimed to see whether clinical healing after amalgam removal corresponds to histologic healing, i.e., a complete disappearance of any histologic sign of lichenoid lesion. STUDY DESIGN: The study evaluated 64 patients with lichenoid lesions and at least one amalgam filling. RESULTS: After amalgam removal, complete clinical healing was obtained in 14 patients (22%) and was significantly related to lesion topography (chi(2) 4.7; P < .05) and positive patch test (chi(2) 6.3; P < .01). Complete histologic healing was obtained in only 7 cases (50% of clinically healed patients), and was significantly related to the combination of positive patch test and strict contact with amalgams (Fisher's exact test P < .01). CONCLUSIONS: Contact with amalgams and positive patch testing are good but not absolute indicators of the beneficial effect of amalgam replacement. In addition, complete clinical healing does not necessarily mean a disappearance of the histologic characteristics of OLL/OLP lesions. PMID- 22668705 TI - Intraoral electrostimulator for xerostomia relief: a long-term, multicenter, open label, uncontrolled, clinical trial. AB - OBJECTIVE: A previous sham-controlled multinational study demonstrated the short term efficacy and safety for xerostomia treatment of an intraoral device that delivers electrostimulation to the lingual nerve. The objective of this study was to test the hypothesis that those beneficial effects would be sustained over an 11-month period. STUDY DESIGN: The device was tested on a mixed sample of 94 patients with xerostomia in an open-label, uncontrolled, prospective multicenter trial. Statutory outcome assessments were done at 5th, 8th, and 11th months and analyzed by multiple comparisons. RESULTS: Improvements achieved at month 5 from baseline were sustained throughout the follow-up period for the primary outcome, xerostomia severity, and the secondary outcomes resting whole salivary flow rate, xerostomia frequency, oral discomfort, and difficulties in speech, swallowing, and sleeping. No significant side effects were detected. CONCLUSIONS: The beneficial effects of a removable intraoral electrostimulating device were sustained for an 11-month period. PMID- 22668706 TI - Ameloblastoma: a multicentric study. AB - OBJECTIVE: The objective of this study was to supplement the current ameloblastoma database by reporting the clinicopathologic features of ameloblastoma from Asia and North America. MATERIALS AND METHODS: Biopsy records of the participating institutes were reviewed for lesions diagnosed as ameloblastoma during the years 1993 to 2009. Slides were reclassified according to the World Health Organization Classification of Odontogenic Tumors in 2005. Clinical information and radiographic features were collected and analyzed. RESULTS: The mean age of the patients +/- SD was 38.27 +/- 17.78 years; 662 patients (51.36%) were men. Mandible (84.26%) outnumbered maxilla and other locations combined in all countries. The number of multilocular radiolucencies (43.40%) was comparable with that of unilocular radiolucencies (42.04%). Follicular pattern was the most common histopathologic pattern (27.70%), followed by plexiform (21.10%) and unicystic pattern (20.71%), respectively. CONCLUSIONS: The clinicopathologic features of ameloblastomas in the present study show some similarities with previous studies; however, minor differences exist. PMID- 22668707 TI - Silver nanoparticles induce apoptosis through the toll-like receptor 2 pathway. AB - OBJECTIVE: The objective of this study was to evaluate the effects of silver nanoparticles (AgNPs) on the Toll-like receptor 2 (TLR-2) pathway in cultured cells. STUDY DESIGN: Human chondrocytes, periodontal ligament (PDL) cells, and SCC-9 cells (squamous cell carcinoma from the tongue) were cultured and subjected to cytotoxicity assays. To evaluate the effects of AgNPs on the TLR-2 pathway, TLR-2 small interfering (si) RNA or TLR-2 antibodies were applied to the chondrocytes, followed by the application of AgNPs. RESULTS: AgNPs induced dose dependent effects on the examined cell types in terms of both cytotoxicity and TLR-2 expression levels. AgNP-mediated apoptosis was reduced after treatment with TLR-2 siRNA in both PDL cells and chondrocytes. Furthermore, functional blocking of TLR-2 with anti-TLR2 antibodies inhibited AgNP-mediated cytotoxicity. AgNPs increased c-Jun phosphorylation, an effect that was reversed after treatment with TLR-2 siRNA. CONCLUSIONS: The results indicate that AgNP-mediated apoptosis most likely occurs via the TLR-2 pathway. PMID- 22668708 TI - An evaluation of the Shandon Papspin liquid-based oral test using a novel cytologic scoring system. AB - OBJECTIVES: The aim of this study was to evaluate a cost-effective oral liquid based cytology screening test, Shandon Papspin (PS). STUDY DESIGN: We compared the diagnostic accuracy of PS with surgical biopsy in 69 patients. Transepithelial cytology specimens were obtained with the use of cervical cytobrushes. Cytology specimens were graded and scored by using a novel oral cytologic grading and scoring system. RESULTS: Histologic diagnosis of dysplasia or malignancy was made in 51/69 cases, and cytology identified 49/51 cases, with a sensitivity of 96% and specificity of 100%. The best cutoff value for distinguishing reactive/mildly dysplastic lesions from high grade/invasive squamous cell carcinoma was determined to be a cytologic score of 3, representing a sensitivity of 95% and specificity of 96%. CONCLUSIONS: PS appears to be an accurate and economical test for detection of high-risk dysplasias and cancers, but the real significance of this method will be its diagnostic accuracy in studies focusing strictly on lesions with a low level of clinical concern. PMID- 22668709 TI - Aberrant keratinization of reticular oral lichen planus is related to elastolysis. AB - OBJECTIVE: Aberrant keratinization is common in oral lichen planus (OLP) on buccal mucosa. Because elastin is crucial for maintaining the nonkeratinized phenotype of oral mucosa, we examined whether inflammatory elastases and the accompanying elastolysis were related to this feature. STUDY DESIGN: Protein and mRNA levels of keratinization-associated keratins (K1/10), nonkeratinization associated keratins (K4/13), elastin, neutrophil elastase, and macrophage metalloelastase (MMP-12) were compared between normal alveolar mucosa and reticular OLP from buccal mucosa. Normal alveolar mucosae were cultured ex vivo on an organ culture system with and without elastase treatment. After 14 days, the mucosae were examined for 4 keratin expressions. RESULTS: The expressions of K1/10 and elastases increased, whereas those of K4/13 and elastin decreased in OLP. The nonkeratinized mucosa in the organ culture began to express K1/10 when elastase degraded the inherent elastin. CONCLUSIONS: Our study demonstrated that elastolysis in reticular OLP may be related to its aberrant keratinization. PMID- 22668710 TI - Position statement of the American Academy of Oral and Maxillofacial Radiology on selection criteria for the use of radiology in dental implantology with emphasis on cone beam computed tomography. AB - A Position Paper Subcommittee of the American Academy of Oral and Maxillofacial Radiology (AAOMR) reviewed the literature since the original position statement on selection criteria for radiology in dental implantology, published in 2000. All current planar modalities, including intraoral, panoramic, and cephalometric, as well as cone beam computed tomography (CBCT) are discussed, along with radiation dosimetry and anatomy considerations. We provide research-based, consensus-derived clinical guidance for practitioners on the appropriate use of specific imaging modalities in dental implant treatment planning. Specifically, the AAOMR recommends that cross-sectional imaging be used for the assessment of all dental implant sites and that CBCT is the imaging method of choice for gaining this information. This document will be periodically revised to reflect new evidence. PMID- 22668711 TI - Magnetic resonance imaging of temporomandibular joint cyst. AB - OBJECTIVE: The objective of this study was to evaluate the magnetic resonance imaging (MRI) and clinical findings of 6 cases with synovial or ganglion cysts occurring in the temporomandibular joint (TMJ). STUDY DESIGN: Six patients with histopathologically confirmed TMJ cysts who were examined by MRI were included in this study. Two oral radiologists retrospectively evaluated MR images. RESULTS: MR images revealed a homogeneous well defined mass of the TMJ in all cases. These cysts demonstrated low signal intensity on proton density-weighted (PDW) and homogeneous very high signal on T2-weighted (T2W) images. They were all characteristically continuous with the joint capsule. Regarding clinical features, all 6 patients had some type of TMJ pain. CONCLUSIONS: TMJ cysts were identified as well defined homogeneous masses with low signal intensity on PDW and very high signal on T2W images, and characterized by continuity with the joint capsule. All of the patients with TMJ cysts exhibited some type TMJ pain. PMID- 22668712 TI - Internal derangement of the temporomandibular joint: is there still a place for ultrasound? AB - OBJECTIVE: The aim of this study was to assess the diagnostic value of articular sounds, standardized clinical examination, and standardized articular ultrasound in the detection of internal derangements of the temporomandibular joint. STUDY DESIGN: Forty patients and 20 asymptomatic volunteers underwent a standardized interview, physical examination, and static and dynamic articular ultrasound. Sensitivity, specificity, and predictive values were calculated using magnetic resonance as the reference test. RESULTS: A total of 120 temporomandibular joints were examined. Based on our findings, the presence of articular sounds and physical signs are often insufficient to detect disk displacement. Imaging by static and dynamic high-resolution ultrasound demonstrates considerably lower sensitivity when compared with magnetic resonance. Some of the technical difficulties resulted from a limited access because of the presence of surrounding bone structures. CONCLUSIONS: The present study does not support the recommendation of ultrasound as a conclusive diagnostic tool for internal derangements of the temporomandibular joint. PMID- 22668713 TI - Skeletal maturity assessment with the use of cone-beam computerized tomography. AB - OBJECTIVE: The aim of the study was to compare cervical vertebrae maturity assessed with the use of cone-beam computerized tomography (CBCT) with the hand wrist maturation method and cervical vertebrae maturation assessed with the use of lateral cephalography for the assessment of skeletal maturity. STUDY DESIGN: Assessment of skeletal maturation was done using skeletal maturity indicators (SMI) from hand-wrist radiography, cervical vertebrae maturity index (CVMI) from CBCT and lateral cephalography (cephalo-CVMI). The Spearman correlation coefficient was used for statistical analysis. RESULTS: We observed a significant relationship between CBCT-CVMI and cephalo-CVMI as well as between CBCT-CVMI and SMI stages. The Spearman correlation coefficient value between CBCT-CVMI and cephalo-CVMI was 0.975 (P < .0001) and between CBCT-CVMI and SMI was 0.961(P < .0001). CONCLUSIONS: Cervical vertebrae maturity assessment with CBCT provided a reliable assessment of pubertal growth spurt, and therefore CBCT can be used to assess skeletal maturity. PMID- 22668714 TI - Orofacial granulomatosis treated with low-level laser therapy: a case report. AB - OBJECTIVES: We report a case of orofacial granulomatosis successfully treated with low-level laser therapy (LLLT). STUDY DESIGN: LLLT was delivered through a diode laser device (Lasemar Eufoton, Trieste, Italy) with the use of a 4-cm defocalized lens and power of 1 W. Treatment was administered in sessions of 5 irradiations of 1 minute each, with a 1-minute interval between 2 subsequent irradiations (power density 0.08 W/cm(2); fluence/application: 4.8 J/cm(2); fluence/session: 24 J/cm(2)). Laser therapy was repeated 12 times (3 times per week). RESULTS: After 2 weeks of LLLT applications, the patient reported an improvement of symptomatology as well as a decrease of labial swelling. Complete healing was observed after 1 month. The patient was followed for 2 years. No recurrence of swelling was observed during the follow-up. CONCLUSIONS: Advantages of the LLLT approach include an absence of side effects, analgesic properties (usually reported after first application), and good patient compliance. PMID- 22668715 TI - Unilateral atrophy of the masticatory muscles and mandibular ramus due to pure trigeminal motor neuropathy: a case report. AB - Pure trigeminal motor neuropathy is a very unusual disease that is characterized by trigeminal motor paralysis without trigeminal sensory disturbances and without the involvement of the other cranial nerves. We report a case of pure trigeminal motor neuropathy in a 70-year-old woman. The diagnosis was based on the results of clinical, electromyographic, and radiologic examinations. Only the motor branch of the left trigeminal nerve was damaged. Atrophy of the left-side masticatory muscles and jaw resulted in facial asymmetry. Magnetic resonance imaging (MRI) of the head and face did not detect any pathologic lesion, with the exception of atrophy and fatty infiltration of the muscles innervated by the left trigeminal motor nerve. The etiology of the patient's pure trigeminal motor neuropathy was undetermined. Patients with suspected trigeminal motor neuropathy should undergo MRI of the head and face to evaluate the sequelae of denervation and to detect an intracranial or extracranial lesion. PMID- 22668716 TI - Psammomatoid juvenile ossifying fibroma: an analysis of 2 cases affecting the mandible with review of the literature. AB - Juvenile ossifying fibroma (JOF) is a rare fibro-osseous neoplasm, defined as a variant of the ossifying fibroma that arises within the craniofacial bones. Two subgroups, juvenile psammomatoid ossifying fibroma (PsJOF) and juvenile trabecular ossifying fibroma, have been delineated by their histology. PsJOF occurs predominantly in the sinonasal and orbital bones. This work reports on 2 cases of extensive PsJOF in the body of the right mandible as well as reviews the literature regarding the radiographic and histologic features, treatment, and prognosis of PsJOF of the jaws. PMID- 22668717 TI - Genial tubercle position and dimensions by cone-beam computerized tomography in a Taiwanese sample. AB - OBJECTIVE: . The aim of this study was to evaluate the position and dimensions of the genial tubercle in a Taiwanese sample. STUDY DESIGN: Cone-beam computerized tomography (CT) records of 90 adult patients with class I or class II skeletal type were used to evaluate the position and dimensions of the genial tubercle and dimensions of the anterior mandible. Subjects were grouped by sex and skeletal type. RESULTS: In all groups, the genial tubercle height was close to the genial tubercle width. The distance from the inferior border of the genial tubercle to the inferior border of the mandible was greater in class II male patients than in class I female patients (P < .05). The anterior mandible in class I male patients was thicker than in class II female patients (P < .05). CONCLUSIONS: The variable position and dimensions of this structure among patients suggest the need for cone-beam CT before attempting genioglossus advancement to treat obstructive sleep apnea. PMID- 22668718 TI - Central odontogenic fibroma of the jawbone: 2 case reports describing its imaging features and an analysis of its DCE-MRI findings. AB - Odontogenic fibroma (OF) is a rare nonepithelial benign tumor arising from the odontogenic mesenchymal tissue in the jawbone. OFs are topographically categorized into 2 types, the central type and peripheral type, and are histopathologically divided into the epithelium-poor type and epithelium-rich type. The radiological findings of central OF commonly include a uni- or multilocular radiolucent area with a well-defined margin, which are similar to those of cysts and other benign tumors of the jawbone. Therefore, it is difficult to distinguish OF from these jawbone lesions on radiographs because of their noncharacteristic radiological findings. In this article, we report the cases of 2 patients with central OF who underwent magnetic resonance (MR) examinations and describe the usefulness of dynamic contrast-enhanced MR imaging for diagnosing OF. PMID- 22668719 TI - Suppression of TRIF-dependent signaling pathway of toll-like receptors by allyl isothiocyanate in RAW 264.7 macrophages. AB - Toll-like receptors (TLR) play a significant role in the induction of innate immune responses that are essential for host defense against invading microbial pathogens. In general, TLRs have two major downstream signaling pathways: myeloid differential factor 88 (MyD88)-dependent and toll-interleukin-1 receptor domain containing adapter inducing interferon-beta (TRIF)-dependent pathways. Allyl isothiocyanate (AITC) found in cruciferous vegetables has an effect on treatment of many chronic diseases. However, the exact molecular targets of AITC are still unidentified. Here, it was investigated whether AITC can modulate TLR signaling pathways and what is the molecular target of AITC in TLRs signaling pathways. AITC suppressed the activation of nuclear factor-kappaB by lipopolysaccharide (LPS) or polyinosinic-polycytidylic acid (poly[I:C]), but not by macrophage activating lipopeptide of 2kDa (MALP-2) or cytosine-phosphate-guanine dinucleotide (CpG DNA). AITC also suppressed the activation of interferon regulatory factor 3 (IRF3) and the expression of interferon inducible protein-10 (IP-10) induced by LPS or poly[I:C]. These results suggest that AITC can modulate TRIF-dependent signaling pathways of TLRs leading to decreased inflammatory gene expression. PMID- 22668720 TI - Molecular mechanisms of IgE mediated food allergy. AB - The purpose of this review is to collate current knowledge and recent advances in molecular mechanism behind the immediate type hypersensitivity of foods. Food allergy is a growing concern of human health in developed as well as developing countries now days. Food allergic reactions are mostly IgE mediated and also known as immediate type hypersensitivity or type I reaction. This review encompasses a wide range of molecular events during IgE mediated reactions like primary exposure of allergens, processing of allergens by antigen presenting cells, role of transcription factors like GATA-3, STAT-6, NF-AT, c-maf, c-kit and NF-kappaB, Treg cells, toll like receptors, cytokines and chemokines, class switch to IgE, FcepsilonR1 receptor, priming of IgE on mast cells or basophils, signaling events followed by secondary exposure of allergens, degranulation and release of mediators like leukotrienes, histamines, prostaglandins, beta hexosaminidase and ultimately anaphylaxis. This review may be helpful to beginners as well as experts working in the field of allergy and immunology because of the stepwise explanations of molecular mechanisms involved in IgE mediated reactions. PMID- 22668746 TI - Cathepsin B-like and hemoglobin-type cysteine proteases: stage-specific gene expression in Angiostrongy cantonensis. AB - Three cysteine protease genes, cathepsin B-like enzyme gene 1, 2 (AC-cathB-1, AC cathB-2) and hemoglobin-type cysteine protease gene (AC-hem) were isolated and described from Angiostrongylus cantonensis adult. The deduced amino acid sequence of Ac-cathB-1 and AC-cathB-2 contain all of the conserved regions of cathepsin B. AC-cathB-2 is similar to a host intrusion-related cysteine protease B from Parelaphostrongylus tenuis, and the AC-hem shares high similarity to legumain from Haemonchus contortus. AC-cathB-1 was expressed significantly higher in L1 as compared with AC-hem, the AC-cathB-2 followed; AC-cathB-2 transcripts in L3 were found increased rapidly and obviously abundant, suggesting that AC-cathB-1 and AC cathB-2 may play an important role in intermediate and final host invasion, separately. The cysteine protease genes were more or less expressed in adult stage excepted for AC-cathB-2. As the AC-cathB-1 and AC-hem highly expressed in adult worms, suggesting AC-hem may activate AC-cathB-1 which involved in the host invasion and feeding process. PMID- 22668747 TI - A pre-marketing ALT signal predicts post-marketing liver safety. AB - Drug induced liver injury during drug development is evidenced by a higher incidence of serum alanine aminotransferase (ALT) elevations in treated versus placebo populations and termed an "ALT signal". We sought to quantify whether an ALT signal in pre-marketing clinical trials predicted post-marketing hepatotoxicity. Incidence of ALT elevations (ALT >= 3 times upper limits normal [* ULN]) for drug and placebo of new chemical entities and approved drugs associated with hepatotoxicity was calculated using the Food and Drug Administration (FDA) website. Post-marketing liver safety events were identified using the FDA Adverse Event Reporting System (AERS). The association of FDA AERS signal score (EB05 >= 2) and excess risk of pre-marketing ALT elevation (difference in incidence of ALT >= 3* ULN in treated versus placebo) was examined. An ALT signal of >= 1.2% was significantly associated with a post marketing liver safety signal (p <= 0.013) and a 71.4% positive predictive value. An absent ALT signal was associated with a high likelihood of post-marketing liver safety; negative predictive value of 89.7%. Daily drug dose information improved the prediction of post-marketing liver safety. A cut-off of 1.2% increase in ALT >= 3* ULN in treated versus placebo groups provides an easily calculated method for predicting post-marketing liver safety. PMID- 22668748 TI - Malignant pleural mesothelioma in US automotive mechanics: reported vs expected number of cases from 1975 to 2007. AB - Until the 1980s, chrysotile asbestos was a component of automotive brakes manufactured in the US. The current OSHA Bulletin (2006) for brake repair cites a single study (Lemen, 2004) which concluded that the number of mesothelioma cases reported in the literature in "end-product users of friction materials" indicated an asbestos-related risk for auto mechanics. However, Lemen (2004) did not compare the reported number of cases to an "expected" value, even though pleural mesothelioma occurs in the general population in the absence of asbestos exposure. We compare the number of malignant pleural mesothelioma (MPM) cases reported in the US literature among auto mechanics between 1975-2007 to an expected value derived from estimated numbers of current and former auto mechanics. A total of 106 cases categorized as mesothelioma or malignant neoplasm of the pleura were found in the literature. Using background incidence rates for MPM of two and three cases per million individuals per year, we estimated that a range of 278-515 cases of non-asbestos-related MPM, respectively, would have occurred in current or former auto mechanics from 1975-2007. Our findings are consistent with the numerous epidemiology studies that have found no increased risk of MPM in auto mechanics. PMID- 22668749 TI - Interpreting the biological relevance of bioinformatic analyses with T-DNA sequence for protein allergenicity. AB - Global regulatory agencies require bioinformatic sequence analysis as part of their safety evaluation for transgenic crops. Analysis typically focuses on encoded proteins and adjacent endogenous flanking sequences. Recently, regulatory expectations have expanded to include all reading frames of the inserted DNA. The intent is to provide biologically relevant results that can be used in the overall assessment of safety. This paper evaluates the relevance of assessing the allergenic potential of all DNA reading frames found in common food genes using methods considered for the analysis of T-DNA sequences used in transgenic crops. FASTA and BLASTX algorithms were used to compare genes from maize, rice, soybean, cucumber, melon, watermelon, and tomato using international regulatory guidance. Results show that BLASTX for maize yielded 7254 alignments that exceeded allergen similarity thresholds and 210,772 alignments that matched eight or more consecutive amino acids with an allergen; other crops produced similar results. This analysis suggests that each nontransgenic crop has a much greater potential for allergenic risk than what has been observed clinically. We demonstrate that a meaningful safety assessment is unlikely to be provided by using methods with inherently high frequencies of false positive alignments when broadly applied to all reading frames of DNA sequence. PMID- 22668750 TI - Researchers' needs for resource discovery and collaboration tools: a qualitative investigation of translational scientists. AB - BACKGROUND: A critical aspect of clinical and translational science (CTS) is interdisciplinary and collaborative research, which increasingly requires a wide range of computational and human resources. However, few studies have systematically analyzed such resource needs of CTS researchers. OBJECTIVE: To improve our understanding of CTS researchers' needs for computational and human resources in order to build useful and useable supporting informatics tools. METHODS: We conducted semistructured interviews of 30 CTS researchers from the University of Michigan, followed by qualitative analysis of the interview transcripts. RESULTS: The analysis identified three recurring themes: the need for the federation of information, the need to address information overload, and the need to humanize computing, including strong and well-informed views about the use of social networking tools for research collaboration. These findings helped us to narrow down the available design choices for assisting CTS researchers, and helped to identify potential deficiencies of well-known theoretical frameworks used to guide our study, with suggestions for future remedies. CONCLUSIONS: The user needs identified through the study, along with concrete design suggestions, provided key design, methodological, and theoretical insights, which are being used to guide the design and development of a CTS resource portal. The results and interview instrument should be useful to other institutions with Clinical and Translational Science Awards that face similar challenges related to helping CTS researchers make more effective use of computational and human resources. PMID- 22668752 TI - Functional outcomes and height restoration for patients with multiple myeloma related osteolytic vertebral compression fractures treated with kyphoplasty. AB - STUDY DESIGN: A retrospective review of pathologic vertebral fractures related to multiple myeloma. OBJECTIVE: To report the functional status and height restoration of 32 patients treated with kyphoplasty for multiple myeloma-related vertebral compression fractures. SUMMARY OF BACKGROUND DATA: Multiple myeloma can cause significant bony resorption, and vertebral involvement is extremely common. Compression fractures due to myelomatous vertebral metastases result in significant pain and can lead to kyphosis and sagittal imbalance. Nonoperative treatment can result in deformity and continued pain, and large surgical procedures have significant morbidity. Percutaneous cement augmentation (kyphoplasty and vertebroplasty) is a minimally invasive technique that can improve pain in these patients. Kyphoplasty also has the potential to provide mild deformity correction in addition to fracture stabilization. METHODS: Study participants were patients with biopsy-proven multiple myeloma presenting with compression fracture treated with kyphoplasty. Data were compiled from patient charts and preoperative and postoperative radiographs. Patient self-reported functional status were obtained through the use of the Oswestry Disability Index. The degree of vertebral body collapse and deformity was evaluated using the method of Genant and analyzed using paired Student t test. RESULTS: Thirty-two consecutive patients who underwent kyphoplasty at a total of 76 levels for myelomatous vertebral compression fractures were identified. Sixteen fractures were at the thoracolumbar junction. The mean age was 64.3 years. The average Genant grade for the involved levels improved from 1.9 preoperative to 1.53 postoperative, which was statistically significant (P<0.0001). The postoperative Oswestry Disability Index score was obtained at a mean of 24 months, with a mean of 29.6%. Complications occurred in 12 (37.5%) patients, all consisting of minimal intraoperative cement extravasation without clinical sequelae. No changes in the neurological status were observed. The average hospital stay was 1.34 days postprocedure. CONCLUSION: Kyphoplasty for vertebral compression fractures due to multiple myeloma is a safe and effective procedure that can lead to pain relief and vertebral height restoration. PMID- 22668751 TI - Mesenchymal stem cell therapy for attenuation of scar formation during wound healing. AB - Scars are a consequence of cutaneous wound healing that can be both unsightly and detrimental to the function of the tissue. Scar tissue is generated by excessive deposition of extracellular matrix tissue by wound healing fibroblasts and myofibroblasts, and although it is inferior to the uninjured skin, it is able to restore integrity to the boundary between the body and its environment. Scarring is not a necessary process to repair the dermal tissues. Rather, scar tissue forms due to specific mechanisms that occur during the adult wound healing process and are modulated primarily by the inflammatory response at the site of injury. Adult tissue-derived mesenchymal stem cells, which participate in normal wound healing, are trophic mediators of tissue repair. These cells participate in attenuating inflammation in the wound and reprogramming the resident immune and wound healing cells to favor tissue regeneration and inhibit fibrotic tissue formation. As a result, these cells have been considered and tested as a likely candidate for a cellular therapy to promote scar-less wound healing. This review identifies specific mechanisms by which mesenchymal stem cells can limit tissue fibrosis and summarizes recent in vivo studies where these cells have been used successfully to limit scar formation. PMID- 22668753 TI - Association between estrogen receptor gene polymorphism and back pain intensity in female patients with degenerative lumbar spondylolisthesis. AB - STUDY DESIGN: Prospective study. OBJECTIVE: To examine the possible association of estrogen receptor alpha (ERalpha) polymorphisms and pain intensity in symptomatic female degenerative spondylolisthesis (DS) patients. SUMMARY OF BACKGROUND DATA: DS has been associated with a significant sex effect. Thus, several studies about the association between the ER gene and osteoarthritis have been reported. However, whether estrogen is associated with pain sensitivity is inconsistent in the existing literatures from both human and animal studies. METHODS: The PvuII and XbaI polymorphisms, bone mineral density at the lumbar spine (LSBMD) and at the femoral neck (FNBMD), pain intensity at the leg and lower back, and radiologic and anthropometric findings were analyzed in 192 patients with DS. RESULTS: There was a significant association between XbaI polymorphism and the visual analog scale score of back pain. The back pain visual analog scale in patients with a GG genotype was significantly higher than in patients with the AG (P<0.05) or the AA (P<0.05) genotypes. In addition, the presence of the CG haplotype was found to be associated with back pain intensity in the haplotype analysis of the PvuII and the XbaI polymorphisms of ERalpha. CONCLUSIONS: These results suggest that the ERalpha gene polymorphism using XbaI restriction enzyme influences the perception of back pain in patients with DS. PMID- 22668754 TI - Polymorphisms in the transcription factor NRF2 and forearm vasodilator responses in humans. AB - OBJECTIVE: Oxidative stress is integral to the development of endothelial dysfunction and cardiovascular disease. As NRF2 is a key transcription factor in antioxidant defense, we aimed to determine whether polymorphisms within the promoter region of the gene encoding NRF2 (NFE2L2) would significantly modify vasodilator responses in humans. METHODS: Associations between the -653A/G (rs35652124), -651G/A (rs6706649), and -617C/A (rs6721961) polymorphisms within the NFE2L2 promoter and vascular function were evaluated in healthy African American (n=64) and white (n=184) individuals. Forearm blood flow (FBF) was measured by strain-gauge venous occlusion plethysmography at baseline and in response to incremental doses of bradykinin or sodium nitroprusside. Forearm vascular resistance (FVR) was calculated as the mean arterial pressure/FBF. RESULTS: In African Americans, -653G variant allele carriers had significantly lower FBF and higher FVR under basal conditions as well as in response to bradykinin or sodium nitroprusside compared with wild-type individuals (P<0.05 for each comparison). In whites, although no significant associations were observed with the -653A/G genotype, -617A variant allele carriers had significantly higher FVR at baseline and in response to bradykinin or sodium nitroprusside compared with wild-type individuals (P<0.05 for each comparison). The -651G/A polymorphism was not associated with vasodilator responses in either racial group. CONCLUSION: Polymorphisms within the NFE2L2 promoter were associated with impaired forearm vasodilator responses in an endothelial independent manner, suggesting an important role of NRF2 in the regulation of vascular function in humans. PMID- 22668755 TI - Intronic variants in SLCO1B1 related to statin-induced myopathy are associated with the low-density lipoprotein cholesterol response to statins in Chinese patients with hyperlipidaemia. AB - Whole-genome studies have identified several intronic single nucleotide polymorphisms (SNPs) in SLCO1B1 associated with simvastatin-induced myopathy. The present study determined the effect of an intronic SNP rs4149081 in SLCO1B1 on the lipid-lowering effects of simvastatin and rosuvastatin in Chinese patients with hypercholesterolaemia. Lipid profiles were determined off treatment and after at least 4 weeks of treatment with each of the statins at daily doses of rosuvastatin 10 mg and simvastatin 40 mg. In 247 patients with good adherence, the rs4149081 G>A polymorphism was significantly associated with a 4.6 and 4.0% greater low-density lipoprotein cholesterol (LDL-C) reduction compared with those with wild-type alleles in response to rosuvastatin and simvastatin, respectively (P<0.05 for both). The 388A>G and 521T>C polymorphisms were not associated with the LDL-C response to either statin. The intronic SNP rs4149081 in SLCO1B1 was associated with the LDL-C response to statins in Chinese patients and this association was independent of the 521T>C polymorphism. PMID- 22668756 TI - Letters to the editor. PMID- 22668757 TI - Radiation dose estimation in computed tomography examinations using NRPB-SR250 software in aretrospective analysis of a patient population. AB - Computed tomography (CT) imaging contributes to a major part of medical radiation exposure. With regard to patients safety, frequent CT examinations (CTEs) performed on the same patient are of particular concern. Tools for tracking the individual patient radiation exposure history and cumulative dose assessment may become important. Here, the applicability of the NRPB-SR250 software was assessed in a retrospective analysis of radiation doses from CTE made consecutively in male patients. Most of the examinations focused on the abdomen or the whole body. The mean number of CTs per patient was 6.8. Significant cumulative effective doses were observed: 76 (66 %) patients received an effective dose higher than 50 mSv, while the maximum was ~280 mSv. A more than 3-fold effective dose difference was observed between scanners, depending on the scanning protocols. The NRPB SR250 software proved to be a robust tool for the assessment of organ doses and the effective radiation dose from CT, while challenges were encountered in finding the precise imaging data in retrospective protocols. PMID- 22668758 TI - An electrical circuit model for simulation of indoor radon concentration. AB - In this study, a new model based on electric circuit theory was introduced to simulate the behaviour of indoor radon concentration. In this model, a voltage source simulates radon generation in walls, conductivity simulates migration through walls and voltage across a capacitor simulates radon concentration in a room. This simulation considers migration of radon through walls by diffusion mechanism in one-dimensional geometry. Data reported in a typical Greek house were employed to examine the application of this technique of simulation to the behaviour of radon. PMID- 22668759 TI - Current clinical research involving cochlear implantation. PMID- 22668760 TI - Current research with cochlear implants at Arizona State University. AB - In this article we review, and discuss the clinical implications of, five projects currently underway in the Cochlear Implant Laboratory at Arizona State University. The projects are (1) norming the AzBio sentence test, (2) comparing the performance of bilateral and bimodal cochlear implant (CI) patients in realistic listening environments, (3) accounting for the benefit provided to bimodal patients by low-frequency acoustic stimulation, (4) assessing localization by bilateral hearing aid patients and the implications of that work for hearing preservation patients, and (5) studying heart rate variability as a possible measure for quantifying the stress of listening via an implant. The long term goals of the laboratory are to improve the performance of patients fit with cochlear implants and to understand the mechanisms, physiological or electronic, that underlie changes in performance. We began our work with cochlear implant patients in the mid-1980s and received our first grant from the National Institutes of Health (NIH) for work with implanted patients in 1989. Since that date our work with cochlear implant patients has been funded continuously by the NIH. In this report we describe some of the research currently being conducted in our laboratory. PMID- 22668762 TI - Studies in pediatric hearing loss at the House Research Institute. AB - Three clinical research projects are described that are relevant to pediatric hearing loss. The three projects fall into two distinct areas. The first area emphasizes clinical studies that track developmental outcomes in children with hearing loss; one project is specific to cochlear implants and the other to hearing aids. The second area addresses speech perception test development for very young children with hearing loss. Although these two lines of research are treated as separate areas, they begin to merge as new behavioral tests become useful in developing protocols for contemporary studies that address longitudinal follow-up of children with hearing loss. PMID- 22668761 TI - Plasticity in the developing auditory cortex: evidence from children with sensorineural hearing loss and auditory neuropathy spectrum disorder. AB - The developing auditory cortex is highly plastic. As such, the cortex is both primed to mature normally and at risk for reorganizing abnormally, depending upon numerous factors that determine central maturation. From a clinical perspective, at least two major components of development can be manipulated: (1) input to the cortex and (2) the timing of cortical input. Children with sensorineural hearing loss (SNHL) and auditory neuropathy spectrum disorder (ANSD) have provided a model of early deprivation of sensory input to the cortex and demonstrated the resulting plasticity and development that can occur upon introduction of stimulation. In this article, we review several fundamental principles of cortical development and plasticity and discuss the clinical applications in children with SNHL and ANSD who receive intervention with hearing aids and/or cochlear implants. PMID- 22668763 TI - Current and planned cochlear implant research at New York University Laboratory for Translational Auditory Research. AB - The Laboratory of Translational Auditory Research (LTAR/NYUSM) is part of the Department of Otolaryngology at the New York University School of Medicine and has close ties to the New York University Cochlear Implant Center. LTAR investigators have expertise in multiple related disciplines including speech and hearing science, audiology, engineering, and physiology. The lines of research in the laboratory deal mostly with speech perception by hearing impaired listeners, and particularly those who use cochlear implants (CIs) or hearing aids (HAs). Although the laboratory's research interests are diverse, there are common threads that permeate and tie all of its work. In particular, a strong interest in translational research underlies even the most basic studies carried out in the laboratory. Another important element is the development of engineering and computational tools, which range from mathematical models of speech perception to software and hardware that bypass clinical speech processors and stimulate cochlear implants directly, to novel ways of analyzing clinical outcomes data. If the appropriate tool to conduct an important experiment does not exist, we may work to develop it, either in house or in collaboration with academic or industrial partners. Another notable characteristic of the laboratory is its interdisciplinary nature where, for example, an audiologist and an engineer might work closely to develop an approach that would not have been feasible if each had worked singly on the project. Similarly, investigators with expertise in hearing aids and cochlear implants might join forces to study how human listeners integrate information provided by a CI and a HA. The following pages provide a flavor of the diversity and the commonalities of our research interests. PMID- 22668764 TI - Cochlear implantation updates: the Dallas Cochlear Implant Program. AB - This report provides an overview of many research projects conducted by the Dallas Cochlear Implant Program, a joint enterprise between the University of Texas at Dallas, the University of Texas Southwestern Medical Center, and Children's Medical Center. The studies extend our knowledge of factors influencing communication outcomes in users of cochlear implants. Multiple designs and statistical techniques are used in the studies described including both cross sectional and longitudinal analyses. Sample sizes vary across the studies, and many of the samples represent large populations of children from North America. Multiple statistical techniques are used by the team to analyze outcomes. The team has provided critical information regarding electrode placement, signal processing, and communication outcomes in users of cochlear implants. PMID- 22668765 TI - The ear is connected to the brain: some new directions in the study of children with cochlear implants at Indiana University. AB - Since the early 1980s, the DeVault Otologic Research Laboratory at the Indiana University School of Medicine has been on the forefront of research on speech and language outcomes in children with cochlear implants. This paper highlights work over the last decade that has moved beyond collecting speech and language outcome measures to focus more on investigating the underlying cognitive, social, and linguistic skills that predict speech and language outcomes. This recent work reflects our growing appreciation that early auditory deprivation can affect more than hearing and speech perception. The new directions include research on attention to speech, word learning, phonological development, social development, and neurocognitive processes. We have also expanded our subject populations to include infants and children with additional disabilities. PMID- 22668766 TI - Assessing spoken word recognition in children who are deaf or hard of hearing: a translational approach. AB - Under natural conditions, listeners use both auditory and visual speech cues to extract meaning from speech signals containing many sources of variability. However, traditional clinical tests of spoken word recognition routinely employ isolated words or sentences produced by a single talker in an auditory-only presentation format. The more central cognitive processes used during multimodal integration, perceptual normalization, and lexical discrimination that may contribute to individual variation in spoken word recognition performance are not assessed in conventional tests of this kind. In this article, we review our past and current research activities aimed at developing a series of new assessment tools designed to evaluate spoken word recognition in children who are deaf or hard of hearing. These measures are theoretically motivated by a current model of spoken word recognition and also incorporate "real-world" stimulus variability in the form of multiple talkers and presentation formats. The goal of this research is to enhance our ability to estimate real-world listening skills and to predict benefit from sensory aid use in children with varying degrees of hearing loss. PMID- 22668768 TI - Knowledge translation in family nursing: does a short-term therapeutic conversation intervention benefit families of children and adolescents in a hospital setting? Findings from the Landspitali University Hospital Family Nursing Implementation Project. AB - In an effort to examine translation of family nursing knowledge to practice, the Landspitali University Hospital Family Nursing Implementation Project (2007 2011), was thoughtfully initiated in Reykjavik, Iceland and systematically evaluated. The mission was to implement family nursing in every department of the hospital. This publication is the first formal research report from this landmark project. The purpose of this research was to evaluate the effectiveness of a short-term therapeutic conversation intervention with families who were receiving health care services at the Children's Hospital at Landspitali University Hospital in Iceland related to childhood and adolescent acute and chronic illnesses. The therapeutic conversation was guided by Family Systems Nursing and used the Calgary Family Assessment and Intervention Models (Wright & Leahey, 2005, 2009). Families (N = 76) were randomly assigned to either an experimental group (short-term therapeutic conversation: n = 41) or to a control group (traditional care: n = 35). Parents in the experimental group reported significantly higher family support after the intervention, compared to the parents in the control group. Differences were noted between families experiencing acute versus chronic illnesses. Recommendations are made for conducting and designing intervention research with families experiencing the hospitalization of a child or adolescent. PMID- 22668767 TI - Studies on bilateral cochlear implants at the University of Wisconsin's Binaural Hearing and Speech Laboratory. AB - This report highlights research projects relevant to binaural and spatial hearing in adults and children. In the past decade we have made progress in understanding the impact of bilateral cochlear implants (BiCIs) on performance in adults and children. However, BiCI users typically do not perform as well as normal hearing (NH) listeners. In this article we describe the benefits from BiCIs compared with a single cochlear implant (CI), focusing on measures of spatial hearing and speech understanding in noise. We highlight the fact that in BiCI listening the devices in the two ears are not coordinated; thus binaural spatial cues that are available to NH listeners are not available to BiCI users. Through the use of research processors that carefully control the stimulus delivered to each electrode in each ear, we are able to preserve binaural cues and deliver them with fidelity to BiCI users. Results from those studies are discussed as well, with a focus on the effect of age at onset of deafness and plasticity of binaural sensitivity. Our work with children has expanded both in number of subjects tested and age range included. We have now tested dozens of children ranging in age from 2 to 14 yr. Our findings suggest that spatial hearing abilities emerge with bilateral experience. While we originally focused on studying performance in free field, where real world listening experiments are conducted, more recently we have begun to conduct studies under carefully controlled binaural stimulation conditions with children as well. We have also studied language acquisition and speech perception and production in young CI users. Finally, a running theme of this research program is the systematic investigation of the numerous factors that contribute to spatial and binaural hearing in BiCI users. By using CI simulations (with vocoders) and studying NH listeners under degraded listening conditions, we are able to tease apart limitations due to the hardware/software of the CI systems from limitations due to neural pathology. PMID- 22668769 TI - Successful treatment of a case of extensive radiation burns with multiple organ dysfunction syndrome. AB - A patient sustained acute third-degree radiation burns over 41% of his body surface. The burns were due to occupational injury caused by an electron accelerator. Most of his wounds appeared and spread gradually during the 10th week after the radiation burn. Subsequently, severe wound infection with methicillin-resistant Staphylococcus aureus, severe pneumonia, respiratory failure, systemic inflammatory response syndrome, nephropathy, and hypoproteinemia had developed 3 months after the radiation injury. Most of the skin grafts could neither survive nor spread on the fresh wound after removing the necrotic tissue. This phenomenon resulted in many more wounds after operations, increasing the risk of wound infection. Parenteral nutrition, respiratory support with a ventilator, antibiotics for methicillin-resistant Staphylococcus aureus, steroid therapeutics for nephropathy, deeper debridement for wounds, and skin grafting were applied for treatment of this patient. The patient recovered gradually and was discharged from the hospital in good condition after 18 months. The authors suggest that deeper excision of necrotic tissue and skin grafting as well as appropriate antibiotics are principal measures to counteract systemic inflammatory response syndrome. Sufficient albumen by vein and steroid should be administered for treatment against nephropathy and for control of infection. Functions of organs should be carefully monitored to fine-tune the therapeutic programs and to minimize complications of organs. PMID- 22668770 TI - Author-created surrogate time intervals misrepresents actual times. PMID- 22668771 TI - Flawed model misrepresents the impact of anesthesiologists to patient safety in the real world. PMID- 22668774 TI - Predictors of failure in timely tuberculosis treatment completion, United States. AB - SETTING: The US tuberculosis (TB) surveillance system. OBJECTIVE: To examine failure in timely TB treatment completion to identify interventions toward achieving the national goal of >= 93% treatment completion in <= 12 months among patients eligible for 6-9 month regimens. DESIGN: We examined 1993-2006 trends in timely treatment completion; for 2006 cases, we used Poisson regression to assess predictors for failure in timely completion. RESULTS: Timely treatment completion improved from 64% in 1993 to 84% in 2006, with similar trends among foreign- and US-born persons and racial/ethnic subgroups. Annual increases in timely completion were <= 1 percentage point during 1998-2006. Subpopulations at highest risk for failure in timely completion were persons with combined pulmonary and extra-pulmonary disease (foreign-born adjusted RR [aRR] 3.25, 95%CI 2.47-4.28; US born aRR 2.75, 95%CI 1.98-3.83) or incarceration (foreign-born aRR 2.30, 95%CI 1.80-2.93; US-born aRR 1.71, 95%CI 1.36-2.14). Homelessness and human immunodeficiency virus infection were other risk factors. CONCLUSIONS: Particular attention to timely completion is needed for subpopulations requiring strong medical expertise in TB management and those at risk for treatment non-adherence, especially if foreign-born. Understanding and addressing causes of delayed completion and improving documentation of treatment completion among all cases will be crucial to achieving the US goal. PMID- 22668776 TI - Constitutive secretion of tau protein by an unconventional mechanism. AB - The microtubule-associated protein tau plays a critical role in the pathogenesis of Alzheimer's disease and several related disorders. In the disease tau aggregates into paired helical and straight filaments, which can form higher order neurofibrillary tangles in neurons and this pathology is associated with progressive neuronal loss and cognitive decline. Tau is a cytoplasmic protein and is thought to be released only from degenerating cells. In contrast, here we provide evidence that tau is constitutively secreted at a low level. We directly show tau release in cell culture model systems. In inducible transfected cell lines we observe that a small proportion of full-length tau is released from intact cells in a time dependent manner. We show that this tau is released by an unconventional secretion process, as the release is temperature dependent but not blocked by inhibitors of the conventional secretory pathway. We characterize the released tau as full length, not vesicle associated and containing Phospho-Tau (181P) proportional to its intracellular concentration. We demonstrate that tau secretion and its suppression by low temperature also occurs in human neurons differentiated from induced pluripotent stem cells. The constitutive tau secretion that we propose provides the most parsimonious explanation for the observed presence of tau in the CSF of healthy animals and human beings. If previously postulated pathogenic extracellular tau intermediates are released by this route, low level constitutive tau secretion could play a role in the spread of tau pathology in Alzheimer's disease and other human tauopathies. PMID- 22668777 TI - Selective knockdown of mutant SOD1 in Schwann cells ameliorates disease in G85R mutant SOD1 transgenic mice. AB - Mutants of superoxide dismutase type 1 (mtSOD1) that have full dismutase activity (e.g., G37R) as well as none (e.g., G85R) cause familial amyotrophic lateral sclerosis (FALS), indicating that mtSOD1-induced FALS results from a toxicity rather than loss in SOD1 enzymatic activity. Still, it has remained unclear whether mtSOD1 dismutase activity can influence disease. A previous study demonstrated that Cre-mediated knockdown of G37R expression in Schwann cells (SCs) of G37R transgenic mice shortened the late phase of disease and survival. These results suggested that the neuroprotective effect of G37R expressed in SCs was greater than its toxicity, presumably because its dismutase activity counteracted reactive oxygen species (ROS). In order to further investigate this, we knocked down G85R in SCs by crossing G85R(flox) mice with myelin-protein-zero (P(0)):Cre mice, which express Cre recombinase in SCs. Knockdown of G85R in SCs of G85R mice delayed disease onset and extended survival indicating that G85R expression in SCs is neurotoxic. These results demonstrate differences in the effect on disease of dismutase active vs. inactive mtSOD1 suggesting that both a loss as well as gain in function of mtSOD1 influence FALS pathogenesis. The results suggest that mtSOD1-induced FALS treatment may have to be adjusted depending on the cell type targeted and particular mtSOD1 involved. PMID- 22668775 TI - Gene therapy for the treatment of chronic peripheral nervous system pain. AB - Chronic pain is a major health concern affecting 80 million Americans at some time in their lives with significant associated morbidity and effects on individual quality of life. Chronic pain can result from a variety of inflammatory and nerve damaging events that include cancer, infectious diseases, autoimmune-related syndromes and surgery. Current pharmacotherapies have not provided an effective long-term solution as they are limited by drug tolerance and potential abuse. These concerns have led to the development and testing of gene therapy approaches to treat chronic pain. The potential efficacy of gene therapy for pain has been reported in numerous pre-clinical studies that demonstrate pain control at the level of the spinal cord. This promise has been recently supported by a Phase-I human trial in which a replication-defective herpes simplex virus (HSV) vector was used to deliver the human pre-proenkephalin (hPPE) gene, encoding the natural opioid peptides met- and leu-enkephalin (ENK), to cancer patients with intractable pain resulting from bone metastases (Fink et al., 2011). The study showed that the therapy was well tolerated and that patients receiving the higher doses of therapeutic vector experienced a substantial reduction in their overall pain scores for up to a month post vector injection. These exciting early clinical results await further patient testing to demonstrate treatment efficacy and will likely pave the way for other gene therapies to treat chronic pain. PMID- 22668778 TI - LRRK2 kinase activity mediates toxic interactions between genetic mutation and oxidative stress in a Drosophila model: suppression by curcumin. AB - Parkinson's disease (PD) is a neurodegenerative disorder characterized by selective loss of dopaminergic neurons and the presence of Lewy bodies. The pathogenesis of PD is believed to involve both genetic susceptibility and environmental factors. Mutations in Leucine-rich repeat kinase 2 (LRRK2) cause genetic forms of PD, and the LRRK2 locus contributes to sporadic PD. Environmental toxins are believed to act in part by causing oxidative stress. Here we employed cell and Drosophila models to investigate the interaction between LRRK2 genetic mutations and oxidative stress. We found that H(2)O(2) increased LRRK2 kinase activity and enhanced LRRK2 cell toxicity in cultured cells and mouse primary cortical neurons. Furthermore, a sub-toxic dose of H(2)O(2) significantly shortened the survival of LRRK2 transgenic flies and augmented LRRK2-induced locomotor defects and dopamine neuron loss. Treatment with a LRRK2 kinase inhibitor (GW5074) or an anti-oxidant (curcumin) significantly suppressed these PD-like phenotypes in flies. Moreover, curcumin significantly reduced LRRK2 kinase activity and the levels of oxidized proteins, and thus acted as not only an antioxidant but also a LRRK2 kinase inhibitor. These results indicate that LRRK2 genetic alterations can interact with oxidative stress, converging on a pathogenic pathway that may be related to PD. These studies also identified curcumin as a LRRK2 kinase inhibitor that may be a useful candidate for LRRK2-linked PD intervention. PMID- 22668780 TI - Mitigation of augmented extrasynaptic NMDAR signaling and apoptosis in cortico striatal co-cultures from Huntington's disease mice. AB - We recently reported evidence for disturbed synaptic versus extrasynaptic NMDAR transmission in the early pathogenesis of Huntington's disease (HD), a late-onset neurodegenerative disorder caused by CAG repeat expansion in the gene encoding huntingtin. Studies in glutamatergic cells indicate that synaptic NMDAR transmission increases phosphorylated cyclic-AMP response element binding protein (pCREB) levels and drives neuroprotective gene transcription, whereas extrasynaptic NMDAR activation reduces pCREB and promotes cell death. By generating striatal and cortical neuronal co-cultures to investigate the glutamatergic innervation of striatal neurons, we demonstrate that dichotomous synaptic and extrasynaptic NMDAR signaling also occurs in GABAergic striatal medium-sized spiny neurons (MSNs), which are acutely vulnerable in HD. Further, we show that wild-type (WT) and HD transgenic YAC128 MSNs co-cultured with cortical cells have similar levels of glutamatergic synapses, synaptic NMDAR currents and synaptic GluN2B and GluN2A subunit-containing NMDARs. However, NMDAR whole-cell, and especially extrasynaptic, current is elevated in YAC128 MSNs. Moreover, GluN2B subunit-containing NMDAR surface expression is markedly increased, irrespective of whether or not the co-cultured cortical cells express mutant huntingtin. The data suggest that MSN cell-autonomous increases in extrasynaptic NMDARs are driven by the HD mutation. Consistent with these results, we find that extrasynaptic NMDAR-induced pCREB reductions and apoptosis are also augmented in YAC128 MSNs. Moreover, both NMDAR-mediated apoptosis and CREB-off signaling are blocked by co-application of either memantine or the GluN2B subunit-selective antagonist ifenprodil in YAC128 MSNs. GluN2A-subunit selective concentrations of the antagonist NVP-AAM077 did not reduce cell death in either genotype. Cortico-striatal co-cultures provide an in vitro model system in which to better investigate striatal neuronal dysfunction in disease than mono cultured striatal cells. Results from the use of this system, which partially recapitulates the cortico-striatal circuit and is amenable to acute genetic and pharmacological manipulations, suggest that pathophysiological NMDAR signaling is an intrinsic frailty in HD MSNs that can be successfully targeted by pharmacological interventions. PMID- 22668781 TI - Activation of subthalamic alpha 2 noradrenergic receptors induces motor deficits as a consequence of neuronal burst firing. AB - The subthalamic nucleus (STN) plays a key role in the pathophysiology of Parkinson's disease. This was demonstrated by the fact that STN neurons express more bursts in animal models of the disease and by the ability of STN inactivation to alleviate motor deficits. However, the origin of the bursts and the causal link between STN bursts and motor deficits remain unknown. The present study aimed to investigate the role of noradrenergic receptor modulation on the firing activity of STN neurons and the impact of this modulation on locomotor activity in sham and 6-hydroxydopamine-lesioned rats. Using selective agonists and antagonists of alpha1- and alpha2-adrenergic receptors (AR), we show that local infusion of clonidine, an alpha2-AR agonist, induced a switch from tonic to bursty pattern without changing the firing rate. This change in the pattern was prevented by the local infusion of idazoxan, an alpha2-AR antagonist. Furthermore, clonidine injection into the STN reduced locomotor activity in sham and 6-hydroxydopamine-lesioned rats. In contrast, local injection of phenylephrine, an alpha1-AR agonist, increased the firing rate of STN neurons without changing the firing pattern. In parallel, phenylephrine did not change locomotor activity. This is the first evidence showing the implication of alpha1 ARs in the modulation of firing rate and alpha2-ARs in the modulation of the firing pattern of STN neurons. Furthermore, our data provide also evidence that activation of the STN alpha2-ARs plays a key role in the genesis of subthalamic burst activity, which may be at the origin of motor deficits. PMID- 22668784 TI - Preoperative predictive model of cervical lymph node metastasis combining fluorine-18 fluorodeoxyglucose positron-emission tomography/computerized tomography findings and clinical factors in patients with oral or oropharyngeal squamous cell carcinoma. AB - OBJECTIVE: This study aimed to construct a preoperative predictive model of cervical lymph node metastasis using fluorine-18 fluorodeoxyglucose positron emission tomography/computerized tomography ((18)F-FDG PET/CT) findings in patients with oral or oropharyngeal squamous cell carcinoma (SCC). STUDY DESIGN: Forty-nine such patients undergoing preoperative (18)F-FDG PET/CT and neck dissection or lymph node biopsy were enrolled. Retrospective comparisons with spatial correlation between PET/CT and the anatomical sites based on histopathological examinations of surgical specimens were performed. We calculated a logistic regression model, including the SUVmax-related variable. RESULTS: When using the optimal cutoff point criterion of probabilities calculated from the model that included either clinical factors and delayed-phase SUVmax >=0.087 or clinical factors and maximum standardized uptake (SUV) increasing rate (SUV-IR) >= 0.100, it significantly increased the sensitivity, specificity, and accuracy (87.5%, 65.7%, and 75.2%, respectively). CONCLUSIONS: The use of predictive models that include clinical factors and delayed-phase SUVmax and SUV-IR improve preoperative nodal diagnosis. PMID- 22668779 TI - The interplay of neuronal mitochondrial dynamics and bioenergetics: implications for Parkinson's disease. AB - The dynamic properties of mitochondria (mitochondrial fission, fusion, transport biogenesis and degradation) are critical for neuronal function and health, and dysregulation of mitochondrial dynamics has been increasingly linked to the pathogenesis of Parkinson's disease (PD). Mitochondrial dynamics and bioenergetics are interconnected, and this is of particular importance in neurons, which have a unique bioenergetic profile due to their energetic dependence on mitochondria and specialized, compartmentalized energetic needs. In this review, we summarize the interplay of mitochondrial dynamics and bioenergetics, and its particular relevance for neurodegeneration. Evidence linking dysregulation of mitochondrial dynamics to PD is presented from both toxin and genetic models, including newly emerging details of how PD-relevant genes PTEN-induced kinase 1 (PINK1) and Parkin regulate fission, fusion, mitophagy and transport. Finally, we discuss how neuronal bioenergetics may impact PD-relevant regulation of mitochondrial dynamics, and possible implications for understanding the role of mitochondrial dynamics in PD. PMID- 22668785 TI - CXCR4 gene transfer prevents pressure overload induced heart failure. AB - Stem cell and gene therapies are being pursued as strategies for repairing damaged cardiac tissue following myocardial infarction in an attempt to prevent heart failure. The chemokine receptor-4 (CXCR4) and its ligand, CXCL12, play a critical role in stem cell recruitment post-acute myocardial infarction. Whereas progenitor cell migration via the CXCL12/CXCR4 axis is well characterized, little is known about the molecular mechanisms of CXCR4 mediated modulation of cardiac hypertrophy and failure. We used gene therapy to test the effects of CXCR4 gene delivery on adverse ventricular remodeling due to pressure overload. We assessed the effect of cardiac overexpression of CXCR4 during trans-aortic constriction (TAC) using a cardiotropic adeno-associated viral vector (AAV9) carrying the CXCR4 gene. Cardiac overexpression of CXCR4 in mice with pressure overload prevented ventricular remodeling, preserved capillary density and maintained function as determined by echocardiography and in vivo hemodynamics. In isolated adult rat cardiac myocytes, CXCL12 treatment prevented isoproterenol induced hypertrophy and interrupted the calcineurin/NFAT pathway. Finally, a complex involving the L-type calcium channel, beta2-adrenoceptor, and CXCR4 (Cav1.2/beta2AR/CXCR4) was identified in healthy cardiac myocytes and was shown to dissociate as a consequence of heart failure. CXCR4 administered to the heart via gene transfer prevents pressure overload induced heart failure. The identification of CXCR4 participation in a Cav1.2-beta2AR regulatory complex provides further insight into the mechanism by which CXCR4 modulates calcium homeostasis and chronic pressure overload responses in the cardiac myocyte. Together these results suggest that AAV9.CXCR4 gene therapy is a potential therapeutic approach for congestive heart failure. PMID- 22668787 TI - Involvement of cholesterol efflux pathway in the control of cardiomyocytes cholesterol homeostasis. AB - Although cholesterol-rich microdomains are highly involved in the functions of cardiomyocytes, the cholesterol homeostasis is largely unknown in these cells. We developed experimental procedures to assess cholesterol synthesis, cholesterol masses and cholesterol efflux from primary cultures of cardiac myocytes obtained from 2 to 4 days old Wistar rats. We first observed that cardiomyocytes poorly internalized exogenously supplied native or modified LDL and that free cholesterol (FC) efflux to free apolipoprotein AI (apo AI) and to HDL was mediated by ATP binding cassette transporter A1 (ABCA1) and likely by ATP binding cassette transporter G1 (ABCG1), respectively, which are both upregulated by liver X receptor/retinoid X receptor (LXR/RXR) activation. We then investigated the consequences of cholesterol synthesis inhibition on cholesterol homeostasis using an HMGCoA reductase inhibitor (pravastatin, 90% effective concentration (EC90): 0.11 mM, 18 h). We observed no impact of cholesterol synthesis inhibition on the FC or cholesteryl ester (CE) masses. Consistently with no FC mass changes, pravastatin treatment had no notable impact on LDL receptors mRNA expression or on the capacity of cardiomyocytes to uptake radiolabeled LDL. Conversely, pravastatin treatment induced a significant decrease of cholesterol efflux to both apo AI and HDL whereas the passive aqueous diffusion remained unchanged. The cholesterol efflux pathway reductions induced by cholesterol synthesis inhibition were not caused by a reduction of ABC transporter expression (mRNA or protein). These results show that cardiac myocytes down-regulate active cholesterol efflux processes when endogenous cholesterol synthesis is inhibited, allowing them to preserve cholesterol homeostasis. PMID- 22668786 TI - Transition metals and mitochondrial metabolism in the heart. AB - Transition metals are essential to many biological processes in almost all organisms from bacteria to humans. Their versatility, which arises from an ability to undergo reduction-oxidation chemistry, enables them to act as critical cofactors of enzymes throughout the cell. Accumulation of metals, however, can also lead to oxidative stress and cellular damage. The importance of metals to both enzymatic reactions and oxidative stress makes them key players in mitochondria. Mitochondria are the primary energy-generating organelles of the cell that produce ATP through a chain of enzymatic complexes that require transition metals, and are highly sensitive to oxidative damage. Moreover, the heart is one of the most mitochondrially-rich tissues in the body, making metals of particular importance to cardiac function. In this review, we focus on the current knowledge about the role of transition metals (specifically iron, copper, and manganese) in mitochondrial metabolism in the heart. This article is part of a Special Issue entitled "Focus on Cardiac Metabolism". PMID- 22668788 TI - DiNuP: a systematic approach to identify regions of differential nucleosome positioning. AB - MOTIVATION: With the rapid development of high-throughput sequencing technologies, the genome-wide profiling of nucleosome positioning has become increasingly affordable. Many future studies will investigate the dynamic behaviour of nucleosome positioning in cells that have different states or that are exposed to different conditions. However, a robust method to effectively identify the regions of differential nucleosome positioning (RDNPs) has not been previously available. RESULTS: We describe a novel computational approach, DiNuP, that compares nucleosome profiles generated by high-throughput sequencing under various conditions. DiNuP provides a statistical P-value for each identified RDNP based on the difference of read distributions. DiNuP also empirically estimates the false discovery rate as a cutoff when two samples have different sequencing depths and differentiate reliable RDNPs from the background noise. Evaluation of DiNuP showed it to be both sensitive and specific for the detection of changes in nucleosome location, occupancy and fuzziness. RDNPs that were identified using publicly available datasets revealed that nucleosome positioning dynamics are closely related to the epigenetic regulation of transcription. AVAILABILITY AND IMPLEMENTATION: DiNuP is implemented in Python and is freely available at http://www.tongji.edu.cn/~zhanglab/DiNuP. CONTACT: yzhang@tongji.edu.cn SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 22668789 TI - SYNCSA--R tool for analysis of metacommunities based on functional traits and phylogeny of the community components. AB - SUMMARY: SYNCSA is an R package for the analysis of metacommunities based on functional traits and phylogeny of the community components. It offers tools to calculate several matrix correlations that express trait-convergence assembly patterns, trait-divergence assembly patterns and phylogenetic signal in functional traits at the species pool level and at the metacommunity level. AVAILABILITY AND IMPLEMENTATION: SYNCSA is a package for the R environment, under a GPL-2 open-source license and freely available on CRAN official web server for R (http://cran.r-project.org). CONTACT: vanderleidebastiani@yahoo.com.br. PMID- 22668790 TI - Bayesian model-based clustering of temporal gene expression using autoregressive panel data approach. AB - MOTIVATION: In a microarray time series analysis, due to the large number of genes evaluated, the first step toward understanding the complex time network is the clustering of genes that share similar expression patterns over time. Up until now, the proposed methods do not point simultaneously to the temporal autocorrelation of the gene expression and the model-based clustering. We present a Bayesian method that considers jointly the fit of autoregressive panel data models and hierarchical gene clustering. RESULTS: The proposed methodology was able to cluster genes that share similar expression over time, which was determined jointly by the estimates of autoregression parameters, by the average level of expression) and by the quality of the fitted model. AVAILABILITY AND IMPLEMENTATION: The R codes for implementation of the proposed clustering method and for simulation study, as well as the real and simulated datasets, are freely accessible on the Web http://www.det.ufv.br/~moyses/links.php. CONTACT: moysesnascim@ufv.br. PMID- 22668791 TI - Borrowing strength: a likelihood ratio test for related sparse signals. AB - MOTIVATION: Cancer biology is a field where the complexity of the phenomena battles against the availability of data. Often only a few observations per signal source, i.e. genes, are available. Such scenarios are becoming increasingly more relevant as modern sensing technologies generally have no trouble in measuring lots of channels, but where the number of subjects, such as patients or samples, is limited. In statistics, this problem falls under the heading 'large p, small n'. Moreover, in such situations the use of asymptotic analytical results should generally be mistrusted. RESULTS: We consider two cancer datasets, with the aim to mine the activity of functional groups of genes. We propose a hierarchical model with two layers in which the individual signals share a common variance component. A likelihood ratio test is defined for the difference between two collections of corresponding signals. The small number of observations requires a careful consideration of the bias of the statistic, which is corrected through an explicit Bartlett correction. The test is validated on Monte Carlo simulations, which show improved detection of differences compared with other methods. In a leukaemia study and a cancerous fibroblast cell line, we find that the method also works better in practice, i.e. it gives a richer picture of the underlying biology. AVAILABILITY: The MATLAB code is available from the authors or on http://www.math.rug.nl/stat/Software. CONTACT: e.c.wit@rug.nl d.bakewell@liv.ac.uk. PMID- 22668792 TI - Genomic dark matter: the reliability of short read mapping illustrated by the genome mappability score. AB - MOTIVATION: Genome resequencing and short read mapping are two of the primary tools of genomics and are used for many important applications. The current state of-the-art in mapping uses the quality values and mapping quality scores to evaluate the reliability of the mapping. These attributes, however, are assigned to individual reads and do not directly measure the problematic repeats across the genome. Here, we present the Genome Mappability Score (GMS) as a novel measure of the complexity of resequencing a genome. The GMS is a weighted probability that any read could be unambiguously mapped to a given position and thus measures the overall composition of the genome itself. RESULTS: We have developed the Genome Mappability Analyzer to compute the GMS of every position in a genome. It leverages the parallelism of cloud computing to analyze large genomes, and enabled us to identify the 5-14% of the human, mouse, fly and yeast genomes that are difficult to analyze with short reads. We examined the accuracy of the widely used BWA/SAMtools polymorphism discovery pipeline in the context of the GMS, and found discovery errors are dominated by false negatives, especially in regions with poor GMS. These errors are fundamental to the mapping process and cannot be overcome by increasing coverage. As such, the GMS should be considered in every resequencing project to pinpoint the 'dark matter' of the genome, including of known clinically relevant variations in these regions. AVAILABILITY: The source code and profiles of several model organisms are available at http://gma-bio.sourceforge.net PMID- 22668793 TI - NetCmpt: a network-based tool for calculating the metabolic competition between bacterial species. AB - NetCmpt is a tool for calculating the competitive potential between pairs of bacterial species. The score describes the effective metabolic overlap (EMO) between two species, derived from analyzing the topology of the corresponding metabolic models. NetCmpt is based on the EMO algorithm, developed and validated in previous studies. It takes as input lists of species-specific enzymatic reactions (EC numbers) and generates a matrix of the potential competition scores between all pairwise combinations. AVAILABILITY AND IMPLEMENTATION: NetCmpt is provided as both a web tool and a software package, designed for the use of non computational biologists. The NetCmpt web tool, software, examples, and documentation are freely available online at http://app.agri.gov.il/shiri/NetComp.php. PMID- 22668794 TI - In vitro inhibition of HBV replication by a novel compound, GLS4, and its efficacy against adefovir-dipivoxil-resistant HBV mutations. AB - BACKGROUND: HBV infection continues to be an important worldwide cause of morbidity and mortality. Patients with chronic hepatitis B can be successfully treated using nucleoside/nucleotide analogues. However, drug-resistant HBV mutants frequently arise, leading to treatment failure and progression to liver disease. Here, we report the effects of GLS4, a non-nucleosidic inhibitor that exhibits a novel and highly specific anti-HBV activity. METHODS: The median inhibitory concentrations (IC(50)s) of GLS4 on HBV were measured by Southern blotting. HBV capsid and core protein levels were detected by immunoblotting. To determine the antiviral activity of GLS4 against adefovir dipivoxil (ADV) resistant HBV mutants, HepG2 cells transiently transfected with PUC-HBV1.2 plasmids that contained one of three major ADV-resistant mutations (rtA181T, rtA181V and rtN236T) were treated with GLS4. Intracellular HBV replicative intermediates were detected by Southern blotting. The effect on the in vitro assembly of HBV capsid protein was examined using dynamic light scattering and electron microscopy. RESULTS: The IC(50) of GLS4 was 0.012 MUM, which is significantly lower than that of lamivudine (0.325 MUM). Immunoblot analysis of HepG2.2.15 cells and transiently transfected HepG2 cells indicated that GLS4 treatment interfered with the formation of core particles (assembly). The ADV resistant HBV mutant strains were also sensitive to GLS4. Upon examining the in vitro assembly of HBV core protein 149 by electron microscopy, increased aberrant particles were observed after GLS4 treatment. CONCLUSIONS: GLS4 is a new and unique potential anti-HBV agent that possesses a different mechanism of action than existing therapeutic drugs. PMID- 22668795 TI - Developing treatment for spinal and bulbar muscular atrophy. AB - Spinal and bulbar muscular atrophy is unique among the polyglutamine diseases in that the toxicity of the mutant protein, the androgen receptor, is ligand dependent. In cell culture and animal models the mutant androgen receptor causes protein aggregation and alterations in transcriptional regulation, axonal transport, and mitochondrial function. Various therapeutic approaches have shown efficacy in mouse models, including androgen reduction and agents that alter the processing and degradation of the mutant androgen receptor protein, such as HSP90 inhibitors, IGF-1, and ASC-J9. Clinical trials of androgen-reducing agents have shown indications of efficacy but not proof of clinically meaningful benefit to date. This trial experience has set the stage for future clinical studies of other agents that have been found to be beneficial in transgenic animal models. PMID- 22668796 TI - Aqueous two-phase system coupled with ultrasound for the extraction of lignans from seeds of Schisandra chinensis (turcz.) Baill. AB - In this study the potential use of an aqueous two phase system (ATPS) coupled with ultrasound for the extraction of lignans from Schisandra chinensis seeds was evaluated and optimized using response surface methodology (RSM). The main bioactive components, schizandrin (SA), schisantherin A (SAA) and deoxyschizandrin (DSA) were selected as markers. The partitioning behavior of lignans in different salt-types of ATPS was compared. The optimization ATPS of 25% (w/w) (NH(4))(2)SO(4) and 19% (w/w) ethanol were selected based on their higher upper phase partitioning coefficient (>74) and the recovery (>93%) for three markers. Using the optimized ATPS solvent, the RMS results showed 20:1 of solvent:solid, 800 W and 61.1 min were the optimal ultrasound assisted extraction conditions, under which 13.10mg/g SA, 1.87 mg/g SAA and 1.84 mg/g DSA were recovered in the upper phase, whereas the wasted stigmas accumulated in the lower phase. Compared with 80% ethanol (v/v) ultrasonic extraction, similar yields were obtained, but the present method exhibited higher extraction purity for the selective extraction of lignans from S. chinensis seeds. PMID- 22668798 TI - Long term effects of low protein diet on depressive symptoms and quality of life in elderly Type 2 diabetic patients. AB - OBJECTIVES: The long term effects of a low protein diet (LPD) on depressive symptoms and the quality of life in elderly Type 2 diabetic are unclear. METHODS: 38 elderly Type 2 diabetic patients with CRD (Stage 3 - 4) were enrolled in the study. After 4 weeks on a normal protein diet regimen (NPD) providing 1.0 g/kg per day, all participants were assigned for 30 months, randomly, to a LPD (0.7 g/kg per day), either 7 days a week (LPD 7/7) or 6 days a week (LPD 6/7). Mini mental state examination (MMSE), activities daily living (ADL), cumulative illness severity (CIRS-IS), geriatric depression scale (GDS-15) and short-form healthy survey (SF- 36) were evaluated every 3 months. RESULTS: Before the LPD regimen creatinine clearance (CrCl), MMSE, ADL, CIRS-IS, GDS-15 and SF-36 were similar in both LPD 7/7 and LPD 6/7 groups. After 30 months, the mean GDS- 15 increased significantly more in LPD 7/7 group than in LPD 6/7 group (p < 0.05). Both mean SF-36 MCS and SF-36 PCS were decreased significantly more in LPD 7/7 group than in LPD 6/7 group (p < 0.05). After 30 months, the decline in CrCl observed was similar in LPD 7/7 and LPD 6/7 groups (2.77 +/- 0.3 and 2.84 +/- 0.3 ml/min/year, respectively). CONCLUSION: In elderly Type 2 diabetic patients, long term effects of LPD 6/7 regimen in comparison to LPD 7/7 are associated with a similar decline in CrCl, but with decreased depressive symptoms and a better quality of life. PMID- 22668797 TI - A randomized phase II study of cilengitide (EMD 121974) in patients with metastatic melanoma. AB - Cilengitide (EMD 121974) is a selective inhibitor of integrins alphavbeta3 and alphavbeta5. The alphavbeta3 promotes the proliferation of tumor-associated endothelial cells and potentially the survival of melanoma cells. We conducted a randomized phase II trial in patients with metastatic melanoma to evaluate the clinical efficacy of cilengitide. Patients with stage IV or unresectable stage III melanoma who were either chemonaive or who had previously received one systemic therapy were enrolled. Patients were randomly assigned to either 500 or 2000 mg of cilengitide administered intravenously twice weekly. The primary aim of this study was to determine the progression-free survival rate at 8 weeks. Tumor samples and blood samples were collected for pharmacodynamic and pharmacokinetic studies. Twenty-nine patients were enrolled, of whom 26 were treated (14 at 500 mg and 12 at 2000 mg). Among those treated, only three were progression free at 8 weeks: two in the 500 mg arm and one in the 2000 mg arm. One patient in the 2000 mg arm showed a prolonged partial response after an initial 28% enlargement of her target lesions. The treatment was well tolerated without clinically significant adverse events. The sole responder and one of two patients with stable disease had no alphavbeta3 expression at baseline. Overall, alphavbeta3 expression was decreased by day 8 of the treatment (P=0.05). Cilengitide was well tolerated by patients in both the treatment arms but had minimal clinical efficacy as a single-agent therapy for metastatic melanoma, and the efficacy was not related to baseline alphavbeta3 expression. PMID- 22668799 TI - Gene expression profile of coronary artery cells treated with nonsteroidal anti inflammatory drugs reveals off-target effects. AB - Nonsteroidal anti-inflammatory drugs (NSAIDs) have come under scrutiny because of the gastrointestinal, renal, and cardiovascular toxicity associated with prolonged use of these drugs. The purpose of this study was to identify molecular targets for NSAIDs related to cellular toxicity with a view to optimize drug efficacy in the clinic. Coronary artery smooth muscle cells and endothelial cells were treated with low (clinically achievable) and high (typically used in preclinical studies) concentrations of celecoxib, NS398, and ibuprofen for 24 hours. NSAIDs-induced gene expression changes were evaluated by microarray analysis and validated by real-time reverse-transcription polymerase chain reaction and western blotting. The functional significance of differentially expressed genes was evaluated by Ingenuity Pathway Analysis. At high concentrations, NSAIDs altered the expression of genes regulating cell proliferation and cell death. NSAIDs also altered genes associated with cardiovascular functions including inflammation, thrombosis, fibrinolysis, coronary artery disease, and hypertension. The gene expression was most impacted by ibuprofen, celecoxib, and NS398, in that order. This study revealed that NSAIDs altered expression of an array of genes associated with cardiovascular events and emphasizes the potential for fingerprinting drugs in preclinical studies to assess the potential drug toxicity and to optimize the drug efficacy in clinical settings. PMID- 22668800 TI - Cardiac biomarkers predict outcome after hospitalisation for an acute exacerbation of chronic obstructive pulmonary disease. AB - PURPOSE: In chronic obstructive pulmonary disease (COPD), cardiovascular system is involved but less is known about role of specific cardiac biomarkers. We aimed to investigate associations between N-terminal pro B-type natriuretic peptide (NT proBNP) and troponin T during hospitalisation with 6-month outcome. METHODS: This was a prospective study conducted in consecutive patients hospitalized for an acute exacerbation of COPD. On admission, and at discharge, NT-proBNP and troponin T were measured, and echocardiography was performed. Hospitalisations and mortality were recorded for 6 months after discharge. RESULTS: We included 127 patients (70 +/- 10 years, 70% men, GOLD III/IV 87%). Left ventricular dysfunction was detected in 70 (55%) patients and diastolic dysfunction was the most common type (53 patients-42%). NT-proBNP and troponin T were elevated on admission in 60% and 36%, and at discharge in 28% and 19% of patients. During follow-up, 53 (42%) patients were hospitalized and 17 (13%) patients died. In Kaplan Meier analysis of survival curves, NT-proBNP on admission distinguished between deceased and surviving patients (p=0.011) whilst troponin T at discharge separated hospitalized and non-hospitalized patients (p=0.017). The adjusted Cox proportional hazard model confirmed these findings: discharge troponin T predicted hospitalisations (hazard ratio 2.89, 95% confidence interval 1.13-7.36) and admission NT-proBNP predicted mortality (hazard ratio 4.20, 95% confidence interval 1.07-14.01). CONCLUSIONS: Elevated NT-proBNP at discharge and troponin T on admission predict outcome in patients hospitalized for an acute exacerbation of COPD. PMID- 22668801 TI - HDL-C: does it matter? An update on novel HDL-directed pharmaco-therapeutic strategies. AB - It has long been recognized that elevated levels of low-density lipoprotein cholesterol (LDL-C) increase the risk of cardiovascular disease (CHD) and that pharmacologic therapy to decrease LDL-C significantly reduces cardiovascular events. Despite the effectiveness of statins for CHD risk reduction, even optimal LDL-lowering therapy alone fails to avert 60% to 70% of CHD cases. A low plasma concentration of high-density lipoprotein cholesterol (HDL-C) is also associated with increased risk of CHD. However, the convincing epidemiologic data linking HDL cholesterol (HDL-C) to CHD risk in an inverse correlation has not yet translated into clinical trial evidence supporting linearity between HDL-C increases and CHD risk reduction. It is becoming clear that a functional HDL is a more desirable target than simply increasing HDL-C levels. Discoveries in the past decade have shed light on the complex metabolic and antiatherosclerotic pathways of HDL. These insights, in turn, have fueled the development of new HDL targeted drugs, which can be classified according to four different therapeutic approaches: directly augmenting the concentration of apolipoprotein A-I (apo A I), the major protein constituent of HDL; indirectly augmenting the concentration of apo A-I and HDL cholesterol; mimicking the functionality of apo A-I and enhancing reverse cholesterol transport. This review discusses the latest in novel HDL directed therapeutic strategies. PMID- 22668802 TI - A review of evidence for transmission of HIV from children to breastfeeding women and implications for prevention. AB - BACKGROUND: Child-to-breastfeeding woman transmission (CBWT) of HIV occurs when an HIV-infected infant transmits the virus to an HIV-uninfected woman through breastfeeding. Transmission likely occurs as a result of breastfeeding contact during a period of epithelial disruption, such as maternal skin fissures and/or infant stomatitis. Despite extensive epidemiologic and phylogenetic evidence, however, CBWT of HIV continues to be overlooked. OBJECTIVE: This article summarizes the available evidence for CBWT from nosocomial outbreaks, during which nosocomially HIV-infected infants transmitted the virus to their mothers through breastfeeding. This article also explores the CBWT risk associated with HIV-infected orphans and their female caretakers, and the lack of guidance regarding CBWT prevention in infant feeding recommendations. METHODS: We searched online databases including PubMed and ScienceDirect for English language articles published from January 1975 to January 2011 using the search terms "HIV," "perinatal," "child-to-mother" and "breastfeeding." The citations from all selected articles were reviewed for additional studies. RESULTS: We identified 5 studies documenting cases of CBWT. Two studies contained data on the number of HIV-infected women, as well as the proportion breastfeeding. Rates of CBWT ranged from 40% to 60% among women reporting breastfeeding after their infants were infected. CONCLUSIONS: Poor infection control practices, especially in areas of high HIV prevalence, have resulted in pediatric HIV infections and put breastfeeding women at risk for CBWT. Current infant feeding guidelines and HIV prevention messages do not address CBWT, and fail to provide strategies to help women reduce their risk of acquiring HIV during breastfeeding. PMID- 22668803 TI - Management of macrolide-resistant Mycoplasma pneumoniae infection. PMID- 22668804 TI - Inflammation in the middle ear of children with recurrent or chronic otitis media is associated with bacterial load. AB - BACKGROUND: Viral upper respiratory tract infections have been described as an important factor in the development of otitis media (OM), although it is unclear whether they facilitate bacterial OM or can directly cause OM. To clarify the role of viral infections in OM, we compared the relative contribution of viruses and bacteria with the induction of inflammatory cytokine responses in the middle ear of children suffering from OM. METHODS: Children up to 5 years of age, with recurrent or chronic episodes of OM and scheduled for ventilation tube insertion were enrolled in a prospective study. Middle ear fluids (n = 116) were collected during surgery, and quantitative polymerase chain reaction was performed to detect bacterial and viral otopathogens, that is, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and 15 respiratory viruses. Finally, concentrations of the inflammatory mediators interleukin (IL)-1beta, IL 6, IL-8, IL-10, IL-17a and tumor necrosis factor-alpha were determined. RESULTS: Middle ear fluids were clustered into 4 groups, based on the detection of viruses (28%), bacteria (27%), both bacteria and viruses (27%) or no otopathogens (19%). Bacterial detection was associated with significantly elevated concentrations of cytokines compared with middle ear fluids without bacteria (P < 0.001 for all cytokines tested) in a bacterial load-dependent and species-dependent manner. In contrast, the presence of viruses was not associated with changes in cytokine values, and no synergistic effect between viral-bacterial coinfections was observed. CONCLUSIONS: The presence of bacteria, but not viruses, is associated with an increased inflammatory response in the middle ear of children with recurrent or chronic OM. PMID- 22668805 TI - A twenty-year retrospective study of pediatric tuberculosis in two tertiary hospitals in Rome. AB - BACKGROUND: Tuberculosis (TB) is among the top 10 causes of child death worldwide. Nevertheless, childhood disease has been neglected by tuberculosis control programs. METHODS: This was a retrospective study of patients < 16 years of age diagnosed with active TB in 2 tertiary hospitals in Rome (Italy), between 1990 and 2009. RESULTS: Two hundred fourteen cases of active tuberculosis were identified (132 definite, 82 probable). Pulmonary involvement was the most common form (75.5%), followed by lymphadenopathy (15.4%) and central nervous system TB (11%). Fever (51.86%) and cough (40%) were the most common presenting symptoms. A total of 23.4% of children were asymptomatic on admission. Sensitivities of the tuberculin skin test and the quantiferon test were 93.4% and 97%, respectively. Both tests performed in 52 children agreed in 49 cases (94%). Sensitivities for culture, Ziehl-Neelsen staining and polymerase chain reaction were 58%, 25% and 66.3%, respectively. The adult source case was identified in 28% of cases. History of contact with a patient with active TB was associated with pulmonary TB (P = 0.0014), whereas negative history of contact was associated with lymph node (P = 0.0064) and central nervous system TB (P = 0.05). CONCLUSIONS: Our study emphasizes the difficulty in managing children with suspected TB, because the absence of constitutional symptoms cannot exclude TB, and bacteriologic confirmation is the exception. Immunologic diagnosis can be a valuable tool to identify TB-infected children because the quantiferon test showed high sensitivity in all age groups. This is of primary importance because early identification of children with latent tuberculous infection and appropriate chemoprophylaxis represent, to date, the most important tool to reduce the burden of TB. PMID- 22668806 TI - Costs of meningitis sequelae in children in Dakar, Senegal. AB - BACKGROUND: Survivors of bacterial meningitis risk lifelong sequelae. In economic evaluations of vaccines protecting against meningitis, treatment and productivity costs due to meningitis sequelae are rarely included in studies from low-income countries, mainly due to lack of data. The aim of this study was to estimate the costs of meningitis sequelae in children in Senegal from the perspective of households. METHODS: Children who had suffered from bacterial meningitis were identified from a database at Albert Royer Hospital in Dakar. Sixty-eight children were located at their home and caregivers interviewed about costs during the acute meningitis episode and due to meningitis sequelae, including productivity loss from caring for a disabled child. Lifetime costs were predicted by assuming a life expectancy of 30 years for disabled children. RESULTS: Seventy one percent of the children had either minor or major sequelae. Mean discounted lifetime sequelae costs amounted to US$ 34,895 (95% confidence interval: US$ 67 96,755) per child. Discounted childcare costs amounted to US$ 3158 (9%), treatment costs US$ 460 (1%) and productivity costs US$ 31,276 (90%). No children were receiving rehabilitation services by the time the study was conducted. CONCLUSION: The present study is the first to present data on household costs from families with disabled children in a low-income country setting. Caring for a disabled child is a considerable financial as well as emotional burden for the individual family. None of the families could afford the treatment they desired for their child. PMID- 22668807 TI - Occurrence of group A beta-hemolytic streptococcal pharyngitis in the four months after treatment of an index episode with amoxicillin once-daily or twice-daily or with cephalexin. AB - BACKGROUND: Prospective studies using bacterial eradication as the endpoint have demonstrated that once-daily amoxicillin is as effective as twice-daily amoxicillin for treatment of group A beta-hemolytic streptococcal (GABHS) pharyngitis. OBJECTIVE: The aim of this study was to determine, in a retrospective study, whether treatment of symptomatic GABHS pharyngitis with once daily amoxicillin was as effective in preventing clinical recurrences as twice daily amoxicillin or cephalexin in pediatric office practice, using patient initiated return visits for streptococcal pharyngitis as a pragmatic, clinical endpoint. METHODS: The charts of consecutive patients 2 years of age and older with laboratory-proven GABHS pharyngitis for a period of 2 years were reviewed to identify index cases of streptococcal pharyngitis and subsequent episodes. Age, weight, antibiotic treatment and time from index to subsequent episodes of GABHS pharyngitis were recorded. RESULTS: In 1402 index episodes, patients received amoxicillin once-daily (231), amoxicillin twice-daily (846) or cephalexin (325). The risk of symptomatic streptococcal pharyngitis in the 4 months after treatment of the index episode was not statistically different among the 3 treatment groups: amoxicillin once-daily (15.1%), amoxicillin twice-daily (19.6%) and cephalexin (19.1%). There was a trend toward reduction in the risk of recurrences in the 6 weeks after completion of antibiotics in the cephalexin (9%) group compared with the combined amoxicillin (13%) groups. CONCLUSIONS: Amoxicillin once-daily or twice-daily was equally effective in terms of frequency of recurrence of symptomatic GABHS pharyngitis. PMID- 22668808 TI - Does the timing of presentation of neck of femur fractures affect the outcome of surgical intervention. AB - OBJECTIVES: There is growing emphasis on minimizing surgical delay for neck of femur fractures. Surgery within 36 h of diagnosis by the emergency department (ED) is classed as a key performance indicator. We aimed to determine the influence of the effect of time of presentation to the ED on surgical delay and 90-day mortality. The influence of age (<85 vs. >=85 years) on these outcomes was also examined. METHODS: A retrospective study was carried out. Data on 663 patients admitted over 30 months to a single unit were analysed for times of presentation to ED, radiographs in ED, admission to trauma ward and surgery. The delays to admission and surgery were calculated. The patients were divided into four 'time classes' depending on their time of presentation in the ED (i.e. 00:00 06:00, 06:00-12:00, 12:00-18:00 and 18:00-00:00) and into two 'age cohorts' (i.e. <85 and >=85 years). RESULTS: The four 'time classes' included 58, 157, 259 and 189 patients, respectively. Patients who presented between 00:00 and 06:00 had a significantly reduced surgical interval and delay (P<0.001). There were no significant differences in the outcome measures, that is 36-h operation and 90 day mortality rates between the four classes. Overall, 386 patients were aged below 85 years and 277 were aged at least 85 years. Admission and surgical delays were similar between the two age cohorts, as were the 36-h operation rates. The 90-day mortality rates were 5.7 and 17.7%, respectively (P<0.0001). CONCLUSION: This study showed that the time of presentation to the ED could influence surgical delay. However, there was no direct relationship between surgical delay and 90-day mortality. PMID- 22668809 TI - Focus on abnormal air: diagnostic ultrasonography for the acute abdomen. AB - Emergency ultrasonography is a frequently used imaging tool in the bedside diagnosis of the acute abdomen. Classic indications include imaging for acute abdominal aneurysm, acute cholecystitis, hydronephrosis, and free intra-abdominal fluid in patients with trauma or suspected vascular or ectopic pregnancy rupture. Point-of-care sonographic imaging often emphasizes the diagnostic utility of fluid and edema, both as a significant finding and as a desirable adjunct for improved imaging. Conversely, the finding of sonographic intra-abdominal air is commonly 'tolerated' as a necessary evil that can foil image acquisition. This is in stark contrast to the accepted diagnostic utility of air in other imaging modalities for the acute abdomen, such as computed tomography and conventional radiography. Countering the bias against air as a deterrent for diagnostic ultrasound's accuracy are several published studies suggesting that abnormal air patterns can be used with high precision to diagnose pneumoperitoneum. These studies advocate that sonographic findings of abnormal air can be straightforward and can become crucial for increasing the diagnostic yield of bedside ultrasound of the acute abdomen. They suggest that practitioners should familiarize themselves with the findings and techniques to gain the experience required to make the diagnosis with confidence. This article will discuss four groups of abnormal air patterns found in the abdomen and the retroperitoneum and the respective scanning techniques, with a focus on the use of ultrasound for diagnosing pneumoperitoneum and a suggested scanning approach in the emergency setting. PMID- 22668810 TI - National survey of emergency departments in Denmark. AB - OBJECTIVES: Emergency departments (EDs) are the basic unit of emergency medicine, but often differ in fundamental features. We sought to describe and characterize EDs in Denmark. METHODS: All EDs open 24/7 to the general public were surveyed using the National ED Inventories survey instrument (http://www.emnet-nedi.org). ED staff were asked about ED characteristics with reference to the calendar year 2008. RESULTS: Twenty-eight EDs participated (82% response). All were located in hospitals. Less than half [43%, 95% confidence interval (CI) 24-63%] were independent departments. Thirty-nine percent (95% CI 22-59%) had a contiguous layout, with medical and surgical care provided in one area. The vast majority of EDs saw both adults and children; only 10% saw adults only and none saw children only. The median number of annual visits was 32 000 (interquartile range, 14 700 47 000). The majority (68%, 95% CI 47-89%) believed that their ED was at good balance or capacity, with 22% responding that they were under capacity and 9% reporting overcapacity. Technological resources were generally available, with the exception of dedicated computed tomography scanners and negative-pressure rooms. Almost all common emergencies were identified as being treatable 24/7 in the EDs. CONCLUSION: Although there is some variation in their layout and characteristics, most Danish EDs have a high degree of resource availability and are able to treat common emergencies. As Denmark seeks to reform emergency care through ED consolidation, this national survey helps to establish a benchmark for future comparisons. PMID- 22668811 TI - Outcomes after minimally invasive esophagectomy: review of over 1000 patients. AB - BACKGROUND: Esophagectomy is a complex operation and is associated with significant morbidity and mortality. In an attempt to lower morbidity, we have adopted a minimally invasive approach to esophagectomy. OBJECTIVES: Our primary objective was to evaluate the outcomes of minimally invasive esophagectomy (MIE) in a large group of patients. Our secondary objective was to compare the modified McKeown minimally invasive approach (videothoracoscopic surgery, laparoscopy, neck anastomosis [MIE-neck]) with our current approach, a modified Ivor Lewis approach (laparoscopy, videothoracoscopic surgery, chest anastomosis [MIE chest]). METHODS: We reviewed 1033 consecutive patients undergoing MIE. Elective operation was performed on 1011 patients; 22 patients with nonelective operations were excluded. Patients were stratified by surgical approach and perioperative outcomes analyzed. The primary endpoint studied was 30-day mortality. RESULTS: The MIE-neck was performed in 481 (48%) and MIE-Ivor Lewis in 530 (52%). Patients undergoing MIE-Ivor Lewis were operated in the current era. The median number of lymph nodes resected was 21. The operative mortality was 1.68%. Median length of stay (8 days) and ICU stay (2 days) were similar between the 2 approaches. Mortality rate was 0.9%, and recurrent nerve injury was less frequent in the Ivor Lewis MIE group (P < 0.001). CONCLUSIONS: MIE in our center resulted in acceptable lymph node resection, postoperative outcomes, and low mortality using either an MIE-neck or an MIE-chest approach. The MIE Ivor Lewis approach was associated with reduced recurrent laryngeal nerve injury and mortality of 0.9% and is now our preferred approach. Minimally invasive esophagectomy can be performed safely, with good results in an experienced center. PMID- 22668812 TI - Upregulated expression of ADAM17 is a prognostic marker for patients with gastric cancer. AB - OBJECTIVE: This study was designed to evaluate the expression and prognostic significance of A Disintegrin and Metalloproteinase17 (ADAM17) protein in patients with gastric cancer. BACKGROUND: Tumor invasion and metastasis are primary causes for treatment failure or death among cancer patients. ADAM17 is a multidomain transmembrane glycoprotein involved in the release of several ligands that were shown to promote tumor formation and progression. Elevated expression of ADAM17 was detected in a number of human cancers and was associated with poor progression and prognosis of the diseases. In gastric cancer, however, the expression and prognostic significance of ADAM17 has not been fully elucidated. METHODS: The expressions of ADAM17 and extracellular matrix metalloproteinase inducer (EMMPRIN), a protein implicated in tumor invasion and metastasis, were detected using the tissue microarray technique and immunohistochemical EnVision method and compared with clinicopathological parameters of patients with gastric cancer. RESULTS: The expressions of ADAM17 and EMMPRIN were upregulated in gastric cancer lesions compared with their expressions in adjacent non-cancerous tissues (P < 0.01). High expression of ADAM17 was detected in 35.78% (156/436) of patients with gastric cancer and positively correlated with the expression of EMMPRIN (r = 0.738, P < 0.01). ADAM17 expression was associated with a number of clinicopathological parameters including depth of invasion and TNM stage of the tumor (P < 0.05). In each TNM stage, patients with high ADAM17 expression had a longer mean survival time than those with low expression (P < 0.05). Particularly, the mean survival time of stage II gastric cancer patients with low ADAM17 expression was longer than that of stage I patients with high ADAM17 expression (P < 0.01). Multivariate survival analysis suggested that, along with other parameters, ADAM17 and EMMPRIN expression were independent prognostic factors for patients with gastric cancer. CONCLUSIONS: ADAM17 was implicated in the progression of gastric cancer. On the basis of the TNM stage, detection of ADAM17 expression will be helpful for predicting prognosis of gastric cancer. PMID- 22668813 TI - Spindle cell carcinoma of the breast: a case report and discussion. AB - Spindle cell carcinoma of the breast is a rare subtype of metaplastic carcinoma with likelihood of aggressive behavior and lack of specific treatment options. Spindle cell carcinomas of the breast are typically "Triple Negative" and have distinct clinical, radiographic and pathological characteristics. We present, in this report, the case of a woman diagnosed with spindle cell carcinoma of the breast, and review the literature on this rare but intriguing disease. PMID- 22668814 TI - Association of ALOX12 and ALOX15 gene polymorphisms with age at menarche and natural menopause in Chinese women. AB - OBJECTIVE: Lipoxygenase (LOX) is one of the major metabolic enzymes for arachidonic acid, which has been reported to be associated with many postmenopausal and many hormone-related diseases. In rats, selective inhibition of the LOX pathway led to defective ovulation. However, little is known about the association of the LOX-related genes with menstruation in women. In this study, we investigated the possible association of two key gene (ALOX12 and ALOX15) polymorphisms with age of menarche and menopause in Chinese women. METHODS: Six tagging single nucleotide polymorphisms (SNPs) of ALOX12 and five SNPs of ALOX15 were genotyped. The association of single SNPs and haplotypes in two candidate genes and age at menarche (AAM) variation was tested in 401 Chinese nuclear families using the quantitative transmissing disequilibrium test. Furthermore, the association between these SNPs and haplotypes and age at natural menopause (AANM) in 710 postmenopausal Chinese women was measured. RESULTS: Using family- and population-based statistical procedures, significant association was found between SNPs rs312462 in ALOX12 and AAM in nuclear families (P = 0.043), and three SNPs (rs2292350, rs312470, and rs312462) in ALOX12 were significantly associated with AANM in postmenopausal women (P = 0.012, P = 0.045, and P = 0.033, respectively). Haplotype analyses corroborated our single SNP results (P = 0.030). However, we failed to find a significant association between ALOX15 gene polymorphisms and AAM as well as AANM (P > 0.05). CONCLUSIONS: Our present results suggest that genetic variations in ALOX12 are associated with both the onset and cessation of menstruation in Chinese women living in Shanghai. PMID- 22668815 TI - The association between polymorphisms in Wnt antagonist genes and bone response to hormone therapy in postmenopausal Korean women. AB - OBJECTIVE: The aim of this study was to explore the association between polymorphisms in Wnt antagonist genes and bone response to hormone therapy (HT) in postmenopausal Korean women. METHODS: A prospective study was conducted with 303 postmenopausal women receiving sequential estrogen plus progestogen therapy in a university hospital. The dickkopf (Dkk) 1 c.318A>G, Dkk2 c.437G>A, Dkk3 c.1003A>G, secreted frizzled-related protein (sFRP) 1 rs3242C>T, rs16890444C>T, sFRP3 c.970C>G, sFRP4 c.958C>A, c.1019G>A, and sFRP5 c.20G>C polymorphisms were analyzed, and bone mineral density (BMD) at the lumbar spine and femoral neck (FN) was measured before and after 1 year of sequential estrogen plus progestogen therapy. RESULTS: The percentage changes in BMD of the FN after 1 year of HT were found to be significantly (P < 0.05) different according to the haplotype genotype composed of the sFRP4 c.958C>A and c.1019G>A polymorphisms after adjustment for baseline BMD. The percentage change in BMD at the FN after 1 year of HT was significantly higher in the AA/AG haplotype genotype than in the AG/CG (P < 0.01) or CG/CG (P < 0.05) haplotype genotype. However, any single and combined polymorphisms measured were not related with nonresponsiveness to HT when a nonresponder was defined as a woman who had lost more than 3% of BMD per year after HT. CONCLUSIONS: The haplotype genotypes of sFRP4 c.958C>A and c.1019G>A polymorphisms are genetic factors that affect changes in BMD of the FN after HT in postmenopausal Korean women. PMID- 22668816 TI - Menopausal hot flashes and insulin resistance. AB - OBJECTIVE: Recent data have indicated that menopausal hot flashes may be a determinant for cardiovascular health. Therefore, we studied the impact of hot flashes on insulin resistance, one of the most powerful markers of cardiovascular health, in recently postmenopausal women. METHODS: We studied 143 recently postmenopausal (amenorrhea 6-36 mo) healthy and normal-weight women without previous hormone therapy use. The women prospectively recorded the number and severity of hot flashes for 2 weeks, and a validated total symptom score, the hot flash weekly weighted score, was calculated for each woman. Insulin resistance was assessed from fasting blood levels of glucose and insulin with the homeostasis model assessment. RESULTS: In 12 women, the assessment of insulin (n = 11) or glucose (n = 1) failed, and they were excluded from further analysis. Thus, hot flashes were absent in 19, mild in 32, moderate in 27, and severe in 53 women. The levels of glucose or insulin, or HOMA showed no differences between these groups, nor was insulin resistance related to the number or severity of hot flashes or to the levels of C-reactive protein or sex hormone-binding globulin. Overall, insulin resistance showed a positive association with body mass index (mean difference, 0.058; 95% CI, 0.015-0.102; P = 0.009) and a negative association with level of estradiol (mean difference, -0.002; 95% CI, -0.003 to 0.001; P = 0.009). CONCLUSIONS: Insulin resistance may not be involved in hot flash-related changes in cardiovascular health. However, because of the small sample size, these findings need to be interpreted with caution. PMID- 22668817 TI - Habitual physical exercise has beneficial effects on telomere length in postmenopausal women. AB - OBJECTIVE: It has been reported that women benefit from the maintenance of telomere length by estrogen. Exercise may favorably influence telomere length, although results are inconsistent regarding the duration and type of exercise and the cell type used to measure telomere length. The purpose of this study was to investigate the relationship between habitual physical exercise and telomere length in peripheral blood mononuclear cells (PBMCs) in postmenopausal women. Postmenopausal women were chosen as study participants because they are typically estrogen deficient. METHODS: This experimental-control, cross-sectional study included 44 healthy, nondiabetic, nonsmoking, postmenopausal women. Habitual exercisers and sedentary participants were matched for age and body mass index. Body weight, height, blood pressure, and waist and hip circumference were measured. Mitochondrial DNA copy number and telomere length in PBMCs were determined, and biochemical tests were performed. Habitual physical exercise was defined as combined aerobic and resistance exercise performed for at least 60 minutes per session more than three times a week for more than 12 months. RESULTS: The mean age of all participants was 58.11 +/- 6.84 years, and participants in the habitual exercise group had been exercising more than three times per week for an average of 19.23 +/- 5.15 months. Serum triglyceride levels (P = 0.01), fasting insulin concentrations (P < 0.01), and homeostasis model assessment of insulin resistance (P < 0.01) were significantly lower and high density lipoprotein cholesterol levels (P < 0.01), circulating adiponectin (P < 0.01), mitochondrial DNA copy number (P < 0.01), and telomere length (P < 0.01) were significantly higher in the habitual exercise group than in the sedentary group. In a stepwise multiple regression analysis, habitual exercise (beta = 0.522, P < 0.01) and adiponectin levels (beta = 0.139, P = 0.03) were the independent factors associated with the telomere length of PBMCs in postmenopausal women. CONCLUSIONS: Habitual physical exercise is associated with greater telomere length in postmenopausal women. This finding suggests that habitual physical exercise in postmenopausal women may reduce telomere attrition. PMID- 22668818 TI - The 2010 North American Menopause Society position statement on hormone therapy goes beyond the available evidence. PMID- 22668820 TI - Ability to follow drug treatment with calcium and vitamin D in postmenopausal women with reduced bone mass. AB - OBJECTIVE: The aim of this study was to evaluate the ability of women with reduced bone mass to follow calcium/vitamin D treatment in relation to prescribed regimen, dose, indication, mode of intake, and the associated factors. METHODS: A cross-sectional study of postmenopausal women taking medication after bone mineral density diagnosis of osteopenia or osteoporosis was conducted using the MedTake questionnaire. A total of 186 patients attending a menopause clinic were studied. Sociodemographic characteristics, history of comorbid conditions, concomitant use of medication, length of medication use, and ability to follow treatment in relation to prescribed regimen, dose, indication, and mode of ingestion were assessed. RESULTS: The mean (SD) age of the women analyzed was 61.6 (8.21) years. The mean time since menopause was 16.8 years. Most women reported having difficulty reading, and 79% were white. The ability to follow treatment, evaluated using MedTake, was lower than 60% in most women. Taking the wrong dose was the most frequent error. The only factor associated with inadequate treatment was the use of concomitant medication (odds ratio, 2.32; 95% CI, 1.06-5.08). CONCLUSIONS: The ability to follow adjuvant calcium and vitamin D treatment for decreased bone mass is low and associated with concomitant use of medication. PMID- 22668821 TI - Involvement of oxidative stress in hypoxia-induced blood-brain barrier breakdown. AB - The blood-brain barrier (BBB) is a cellular barrier formed by specialized brain endothelial cells under the influence of astrocytes and pericytes. Among the several stress factors known to induce BBB breakdown, hypoxia is probably the most represented but also the least understood. Recent evidence of oxidative stress occurring during hypoxia/ischemia situation raises its possible contribution to barrier breakdown. In this study, we investigated the relevance of oxidative stress in hypoxia-induced barrier disruption. Prolonged hypoxic exposure induced reactive oxygen species (ROS) formation and induced glutathione oxidation. Such effects were accentuated under extreme O(2) deprived environment. Pro-oxidant treatment significantly disrupted barrier function under normal conditions, whereas anti-oxidant treatment contributed to maintain better barrier function and cell survival in an O(2)-reduced environment. In addition, the endothelial response to oxidative stress appeared modulated by the presence of astrocytes and pericytes, thus explaining some of the beneficial contribution of these cells as previously described. Taken together, this study highlights the importance of oxidative stress signaling at the barrier. In addition, cells of the neurovascular compartment differentially modulate ROS levels and also regulate barrier function. Thus, use of reactive oxygen scavengers may be useful to support barrier function following stroke injury. PMID- 22668822 TI - Heterogeneous sensitivity of cerebral and muscle tissues to acute normobaric hyperoxia at rest. AB - The purpose was to investigate the effects of acute normobaric hyperoxia at rest on cerebral, respiratory and leg muscle oxygenation. Ten healthy men were studied twice in a single-blinded counterbalanced crossover study protocol. On one occasion they breathed air and on the other 100% normobaric O(2) for a 2-hour time period. Oxygenated (Delta[O(2)Hb]), deoxygenated (Delta[HHb]) and total (Delta[tHb]) hemoglobin in the cerebral frontal cortex, and in the intercostal and vastus lateralis muscles were simultaneously monitored with near-infrared spectroscopy. The hyperoxic stimulus promptly increased Delta[O(2)Hb] (~2 MUM) and decreased Delta[HHb] (~3.6 MUM) in the frontal cortex. These cerebral responses were directly and fully countered by resumption of normoxic air breathing. In contrast, Delta[HHb] significantly decreased due to the acute hyperoxic stimulus in both intercostal and vastus lateralis muscles. The temporal changes in muscle oxygenation were slower compared to those in the cerebral area; and they only partially recovered during the 15-min normoxic-recovery period. Acute supplementation of normobaric O(2) at rest influences cerebral, leg and respiratory muscle oxygenation of healthy individuals, but not in the same manner. Namely, the frontal cortex seems to be more sensitive to hyperoxia than are the skeletal muscle regions. PMID- 22668823 TI - Deep brain stimulation: linking structure and function in awake and anesthetized patients. PMID- 22668824 TI - New frontiers in ethnomedicine: exploring the Angolan indigenous pharmacopeia for novel antimalarial drugs. PMID- 22668825 TI - A biochemically semi-detailed model of auxin-mediated vein formation in plant leaves. AB - We present here a model intended to capture the biochemistry of vein formation in plant leaves. The model consists of three modules. Two of these modules, those describing auxin signaling and transport in plant cells, are biochemically detailed. We couple these modules to a simple model for PIN (auxin efflux carrier) protein localization based on an extracellular auxin sensor. We study the single-cell responses of this combined model in order to verify proper functioning of the modeled biochemical network. We then assemble a multicellular model from the single-cell building blocks. We find that the model can, under some conditions, generate files of polarized cells, but not true veins. PMID- 22668826 TI - Association between 5HTT, DAT1, and DRD4 and bipolar disorder in youth. PMID- 22668827 TI - Suicide risk in youth with intellectual disabilities: the challenges of screening. AB - Children and adolescents with intellectual disabilities (IDs), often diagnosed with comorbid psychiatric disorders, are a vulnerable population who may be at risk for developing suicidal thoughts and behaviors. Previous research has demonstrated that direct suicide screening can rapidly and effectively detect suicide risk and facilitate further clinical evaluation and management. Currently, there are no measures that screen for suicide risk designed specifically for individuals with ID. A review of the literature was conducted to (1) estimate the prevalence of suicidal thoughts, behaviors, and deaths by suicide in children and adolescents with ID; (2) describe associations between youth with ID and suicide risk; and (3) identify the limitations of commonly used suicide screening measures developed for non-ID youth. The literature review confirms that suicide risk exists in this population; youth with ID think about, attempt, and die by suicide. Standardized suicide risk screening is challenged by the lack of measures developed for this population. A summary of the findings is followed by a discussion of the practical clinical considerations surrounding the assessment of suicide risk in youth with ID. PMID- 22668828 TI - Glioblastoma cancer stem cells--from concept to clinical application. AB - Ten years after the first description of cancer stem cells (CSCs) in glioblastoma (GBM), the initial concept of CSC has been challenged and our understanding of cellular heterogeneity within malignant brain tumors became more complex. The increasing knowledge on CSC also influences preclinical research and clinical practice. This review therefore describes current concepts and controversies on CSC in GBM and summarizes the recent progress how the CSC hypothesis is about to translate into preclinical and clinical application. PMID- 22668829 TI - Dimer interface rearrangement of the 6-phosphofructo-2-kinase/fructose 2,6 bisphosphatase rat liver isoenzyme by cAMP-dependent Ser-32 phosphorylation. AB - The bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK 2/FBPase-2) is a key regulator of carbohydrate metabolism in liver. The goal of this study was to elucidate the regulatory role of Ser-32 phosphorylation on the kinase domain mediated dimerization of PFK-2/FBPase-2. Fluorescence-based mammalian two-hybrid and sensitized emission fluorescence resonance energy transfer analyses in cells revealed preferential binding within homodimers in contrast to heterodimers. Using isolated proteins a close proximity of two PFK 2/FBPase-2 monomers was only detectable in the phosphorylated enzyme dimer. Thus, a flexible kinase interaction mode exists, suggesting dimer conformation mediated coupling of hormonal and posttranslational enzyme regulation to the metabolic response in liver. PMID- 22668830 TI - Physical inactivity and risk of hospitalisation for chronic obstructive pulmonary disease. AB - The association between physical activity and risk of hospitalisation for chronic obstructive pulmonary disease (COPD) is not yet clear. We conducted a systematic review of the literature to fill this gap in knowledge. Eight electronic databases were searched using a selection of controlled vocabulary and keywords. The search resulted in more than 1000 initial hits, of which four met the inclusion criteria. For each identified study, relevant data were extracted and appraised. The results indicate that less physically active patients with COPD were more likely to be admitted to hospital. Consistent with a lower level of physical activity, the patients tended to have shorter walking times as well as spend fewer hours outdoors. In multivariate regression analysis, self-reported physical activity predicted hospitalisation in patients from the general population and re-hospitalisation in patients admitted for an acute exacerbation. The evidence for an association between physical activity and risk of hospitalisation for COPD is limited to a few prospective cohort studies. More research is needed to quantify the degree of physical activity associated with reduced risk of hospitalisation. PMID- 22668832 TI - Adalimumab for the prevention of recurrence after surgery for Crohn's disease. PMID- 22668831 TI - Constitutively active TRPC channels of adipocytes confer a mechanism for sensing dietary fatty acids and regulating adiponectin. AB - RATIONALE: Calcium entry is pivotal in the heart and blood vessels, but its significance and mechanisms in adipose tissue are largely unknown. An important factor produced by adipocytes is adiponectin, which confers myocardial protection, insulin-sensitization, and antiatherosclerotic effects. OBJECTIVE: To investigate the relevance of calcium channels to adipocytes and the production of adiponectin. METHODS AND RESULTS: Microarray analysis led to identification of transient receptor potential canonical (TRPC)1 and TRPC5 as channel subunits that are induced when adipocytes mature. Both subunits were found in perivascular fat of patients with atherosclerosis. Intracellular calcium and patch-clamp measurements showed that adipocytes exhibit constitutively active calcium permeable nonselective cationic channels that depend on TRPC1 and TRPC5. The activity could be enhanced by lanthanum or rosiglitazone, known stimulators of TRPC5 and TRPC5-containing channels. Screening identified lipid modulators of the channels that are relevant to adipose biology. Dietary omega-3 fatty acids (eg, alpha-linolenic acid) were inhibitory at concentrations that are achieved by ingestion. The adipocyte TRPC1/TRPC5-containing channel was functionally negative for the generation of adiponectin because channel blockade by antibodies, knock down of TRPC1-TRPC5 in vitro, or conditional disruption of calcium permeability in TRPC5-incorporating channels in vivo increased the generation of adiponectin. The previously recognized capability of alpha-linolenic acid to stimulate the generation of adiponectin was lost when calcium permeability in the channels was disrupted. CONCLUSIONS: The data suggest that TRPC1 and TRPC5 contribute a constitutively active heteromultimeric channel of adipocytes that negatively regulates adiponectin and through which omega-3 fatty acids enhance the anti inflammatory adipokine, adiponectin. PMID- 22668835 TI - Efficacy of sunlight-activatable porphyrin formulates on larvae of Anopheles gambiae M and S molecular forms and An. arabiensis: a potential novel biolarvicide for integrated malaria vector control. AB - Biolarvicides, such as microbial formulations based on Bacillus thuringiensis and B. sphaericus, have been found to be highly effective against mosquito larvae and are currently employed as eco-friendly alternatives to synthetic chemical insecticides for vector control. Recently, a porphyrin of natural origin has been suggested as a sunlight-activatable larvicide against the dengue vector Aedes aegypti. In order to validate the approach for the control of the malaria vector, we tested the photo-larvicidal activity of a novel porphyrin, namely meso-tri(N methyl-pyridyl), mono(N-dodecyl-pyridyl)porphine, C12, associated with two specifically selected carriers, against Anopheles gambiae s.s. and An. arabiensis larvae, both laboratory reared and collected from malaria endemic sites in Burkina Faso. Both C12-porphyrin formulates, when administered to larvae at a 50MUM porphyrin dose, were accumulated in the alimentary canal. Subsequent exposure of the porphyrin-loaded larvae to sunlight for short times (0.5-3h) led to a complete mortality. The high efficacy exhibited by a "foodstuff" porphyrin formulate also in the presence of typical larval food particles opens promising perspectives for the development of an effective photocidal larvicide. PMID- 22668836 TI - Nuclease activity and ultrastructural effects of new sulfonamides with anti leishmanial and trypanocidal activities. AB - Our aim was to evaluate the in vitro efficacy of a series of N benzenesulfonamides of amine substituted aromatic rings, sulfonamides 1-6, against Trypanosoma cruzi and Leishmania spp. and to compare their trypanocidal and leishmanicidal profile. In order to elucidate the probable mechanism of action, the interaction of selected sulfonamides with pUC18 plasmid DNA was investigated by nuclease activity assays. In addition, the cellular targets of these sulfonamides in treated parasites were also searched by transmission and scanning electron microscopy. The most active compounds 4-nitro-N-pyrimidin-2 ylbenzenesulfonamide 1a and 4-chloro-N-5-methyl-thiazol-2-yl-benzenesulfonamide 2d displayed significant in vitro activity against Leishmania spp. promastigotes, without toxicity to J774 macrophages. Selected sulfonamides 1a, 4-nitro-N-pyrazin 2-yl-benzenesulfonamide 1n and 2d were also active against Leishmania infantum intracellular amastigotes. Compounds 1n and 2d showed nuclease activity in the presence of copper salt analogous to our previous results with sulfonamide 1a. Mechanistic data reveal the involvement of a redox process. Evidence for the formation of reactive oxygen species (ROS) responsible for DNA strand scission is provided for sulfonamides 1a, 1n and 2d. Transmission electron microscopic (TEM) analysis of L. infantum promastigotes treated with compounds 1a, 1n and 2d shows an overall cellular disorganization effects which are mainly addressed to DNA bearing structures such as the nucleus, mitochondria and kinetoplast. Disruption of double nuclear membrane and loss of cellular integrity along with accumulation of cytoplasmic electrodense bodies were also frequently observed. PMID- 22668838 TI - Role of a food box program in fruit and vegetable consumption and food security. AB - PURPOSE: We examined whether participation in a food box program has a positive effect on fruit and vegetable consumption and food security. METHODS: Participants and nonparticipants in a food box program were surveyed to determine differences between the two groups and change over time. RESULTS: Fruit and vegetable intake declined in those who left the program after several months, and intake of fruit, carrots, and vegetables was lower among those who had left than among those who remained in the program. Food insecurity was associated with lower intakes of fruit and vegetables. CONCLUSIONS: Participation in a food box program can provide some benefit in terms of increased fruit and vegetable consumption for those who use the program regularly. Increasing the frequency of the box and encouraging continued use may improve these effects. PMID- 22668837 TI - Genetic polymorphisms of Echinococcus granulosus sensu stricto in the Middle East. AB - Echinococcus granulosus sensu stricto is a cosmopolitan parasite causing cystic echinococcosis in humans and livestock. Recent molecular phylogeographic studies suggested the rapid dispersal of the parasite by the anthropogenic movement of domestic animal hosts. In the present study, genetic polymorphism of E. granulosus s. s. in the Middle East, where the domestication started, was investigated to validate the dispersal history of the parasite. Thirty-five and 26 hydatid cysts were collected from Iran and Jordan, respectively, and mitochondrial cytochrome c oxidase subunit I (cox1) gene was sequenced. Chinese and Peruvian specimens were also analyzed for comparison. Haplotype network analysis demonstrated the existence of a common haplotype EG01 in all populations. Although EG01 and its one-step neighbors were the majority in all regions, most of the neighboring haplotypes were unique in each locality. Haplotype diversity was high but nucleotide diversity was low in Iran, Jordan and China. Both diversities were lowest and only a few haplotypes were found in Peru. Neutrality indices were significantly negative in Iran, Jordan and China, and positive but not significant in Peru. Pairwise fixation index was significant for all pairwise comparisons, indicating genetic differentiation among populations. These results suggest a evolutionary history of E. granulosus s. s. in which a genetic subgroup including EG01 was selected at the dawn of domestication, and then it was rapidly dispersed worldwide through the diffusion of stock raising. To approach the origin of the ancestral strain, extensive sampling is needed in many endemic regions. To evaluate the hypothetical evolutionary scenario, further study is needed to analyze specimens from diverse host species in wider regions. PMID- 22668839 TI - Food consumption patterns in preschool children. AB - PURPOSE: Healthy eating during early childhood is important for growth and development. Eating Well with Canada's Food Guide (CFG) provides dietary recommendations. We investigated patterns of food consumption among preschool children and attempted to determine whether these children's intakes met nutrition recommendations. METHODS: Between 2005 and 2007, four- and five-year old children (n=2015) attending 12 Edmonton-region public health units for immunization were recruited for a longitudinal study on determinants of childhood obesity. The children's dietary intake at baseline was assessed using parental reports. RESULTS: Overall, 29.6%, 23.5%, 90.9%, and 94.2% of the children met recommendations for vegetables and fruit, grain products, milk and alternatives, and meat and alternatives, respectively. In addition, 79.5% consumed at least one weekly serving of foods in the "choose least often" group. Significant differences existed in consumption of food groups across socioeconomic and demographic groups. For example, 82.9%, 84.7%, and 75.9% of preschool children from neighbourhoods of low, medium, and high socioeconomic status, respectively, consumed at least one food in the "choose least often" group (chi2 =16.2, p<0.001). CONCLUSIONS: Consumption of vegetables and fruit and grain products was low among participants, and intake of "choose least often" foods was high. Consumption of foods also differed among socioeconomic and demographic groups. To encourage healthy eating among children, public health professionals should target groups who do not meet the CFG recommendations. PMID- 22668840 TI - Inadequate dietary intakes among pregnant women. AB - PURPOSE: Eating behaviours were assessed among pregnant women in a mid-sized Canadian city. METHODS: As part of the Prenatal Health Project, we interviewed 2313 pregnant women in London, Ontario. Subjects also completed a food frequency questionnaire. Recruitment took place in ultrasound clinics at 10 to 22 weeks of gestation. The main outcome measures were number of daily servings for each food group, measured against the minimum number recommended by the 2007 Eating Well with Canada's Food Guide (CFG), the proportion of women consuming the recommended number of servings for each and all of the four food groups, and factors associated with adequate consumption. We also determined the number of servings of "other foods." Analysis included descriptive statistics and logistic regression, all at p<0.05. RESULTS: A total of 3.5% of women consumed the recommended number of servings for all four food groups; 15.3% did not consume the minimum number of servings of foods for any of the four food groups. Women for whom this was their first pregnancy were less likely to consume the recommended number of servings from all four food groups (odds ratio=0.41; confidence interval=0.23, 0.74). CONCLUSIONS: Very few pregnant women consumed food group servings consistent with the 2007 recommendations. Strategies to improve dietary behaviours must focus on the establishment of healthy eating behaviours among women of reproductive age. PMID- 22668841 TI - Body image, body mass index, and body composition in young adults. AB - PURPOSE: Associations were examined between body image and body mass index (BMI) in comparison with body composition in healthy weight, overweight, and obese young adults. METHODS: Weight and height were determined, and the percentage of fat mass (%FM) and percentage of fat-free mass (%FFM) were measured by dual energy X-ray absorptiometry in 75 male and 87 female young adults (21.1 +/- 1.9 years; 25.2 +/- 4.4 kg/m2 [mean +/- standard deviation]). Body image was measured using the three subscales Weight Esteem, Appearance Esteem, and External Attribution of the Body-Esteem Scale for Adolescents and Adults (BESAA). RESULTS: Body mass index and %FM were highly correlated (r for males = 0.74, r for females = 0.82; both p<0.001), and were inversely associated with body image, particularly Weight Esteem. After adjustment for physical activity, BMI and %FM (and %FFM, although in the opposite direction) were associated with each BESAA subscale: %FM, %FFM, and BMI explained 12% to 14% of the variance in Appearance Esteem for both sexes, 33% to 41% in Weight Esteem in women and 16% to 18% in men, and 8% to 10% in External Attribution in women (all p<0.05) and <5% for men (NS). CONCLUSIONS: Clinicians should be aware that as their clients' BMI and %FM increase, body image decreases, particularly in women. PMID- 22668842 TI - Unsuccessful dietetic internship applicants: a descriptive survey. AB - PURPOSE: We examined the demographic characteristics of applicants who applied and were unsuccessful in securing an internship position, what these applicants did afterward in their efforts to obtain an internship position, and which career paths they pursued. We also searched for any differences in eligibility between applicants who had not obtained an internship position and those who eventually were successful. METHODS: A 68-item online survey was administered. RESULTS: The study sample (n=84) was relatively homogeneous: female (99%), heterosexual (98%), Caucasian (70%), Canadian-born (75%), having English as a first language (73%), multilingual (40%), and having completed a previous degree (29%). Mean self reported cumulative grade point average (3.35) exceeded the minimum (3.0) required by most Ontario internship programs. Over 25% eventually secured an internship position. Applicants who rated their packages strong in community nutrition were less successful in attaining an internship. Little difference in qualification was found between those who were eventually successful and not-yet successful applicants. CONCLUSIONS: Unsuccessful applicants met academic and other requirements for admission to dietetic internship programs in Ontario. Insufficient training opportunities, costs associated with internship, and competition may be contributing to a loss of human potential in dietetics. PMID- 22668843 TI - Body dissatisfaction among middle-aged and older women. AB - With the growing pervasiveness of mass media, individuals of all ages and both sexes are bombarded with images that glorify youthfulness, messages that tie self worth to thinness, and products that promise youth and beauty forever. Aging women are vulnerable to these societal messages and experience strong pressures to maintain their youth and thinness. As the physiological changes that accompany normal aging move these women farther from the "ideal" image, body dissatisfaction may increase. These women are confronted with the impossible task of trying to defy the natural process of aging through a variety of means, including fashion, cosmetics, selective surgeries, and personal food choices. The resulting body image issues, weight preoccupation, and eating disturbances can lead to voluntary food restriction, depression, social withdrawal, lower self esteem, and disordered eating, all of which can have a negative impact on quality of life and nutritional status. In this review we explore existing research on body dissatisfaction among middle-aged (30 to 60) and older (over 60) women, discuss the prevalence of body dissatisfaction, its predisposing risk factors, and the resulting eating and body maintenance behaviours, and examine implications for dietetic practice. PMID- 22668844 TI - Dietitians and eating disorders: an international issue. AB - The prevalence of eating disorders is higher in university nutrition faculties than in other faculties. We examined beliefs about and approaches to eating disorders in nutrition education faculties around the world. We developed a questionnaire specifically for this project and distributed 664 copies electronically, using contact information obtained in collaboration with Dietitians of Canada and the International Confederation of Dietetic Associations. Using the 101 questionnaires returned from 14 countries, we found that 77% of respondents felt eating disorders are a concern among nutrition students; however, only 15% of programs had policies/procedures to help address these disorders. Forty-eight percent of respondents thought screening for eating disorders would be a good idea; however, 78% of them believed screening would involve ethical issues. In conclusion, eating disorders are a concern in nutrition faculties around the world, and while most feel something should be done, ethical dilemmas contribute to confusion over the best approach. More work is needed in this area. PMID- 22668845 TI - A team-based approach to qualitative inquiry: the collaborative retreat. AB - A team of researchers undertook a collaborative qualitative study to explore beginning dietitians' life experiences and the meaning ascribed to those experiences in the context of dietetic practice. Data were collected using Seidman's three-step in-depth phenomenological interviewing method with 12 beginning dietitians who were graduates of the three participating dietetic programs. We outline the collaborative research process and highlight a writing and data analysis technique described as the collaborative retreat, a face-to face, two-day gathering that facilitated the researchers' collective decision making and organization, discussion, and analysis of this complex qualitative data set. Use of a listening guide aided researchers' understanding and interpretation of participant voices. Researchers concluded that the overall collaborative qualitative research process was positive and self-fulfilling, and that it resulted in multiple benefits for them individually and the research project collectively. Researchers were able to work through methodological and theoretical issues as these arose, with the assistance of technology, writing, listening, and dialogue. Relationship building and relationship maintenance emerged as factors critical to the success of the research process. Collaborative research teams that are committed to listening, writing, and dialogue will find that the collaborative retreat can be a productive site of knowledge generation and mentorship. PMID- 22668846 TI - Formation of trans fats during food preparation. AB - PURPOSE: An investigation was completed to determine how typical cooking procedures used in food preparation, such as baking and stir-frying, affect trans fats formation. METHODS: Canola oil was used as the main fat ingredient. Zucchini cake and gingersnap cookies were baked at 180o C and 200o C, while stir-fried chicken was prepared at 200o C and 275o C. The lipids from the food were extracted following the Folch procedure, and analyzed for trans fatty acids according to ISO official method 15304. RESULTS: Minimal changes were observed in the amount of trans fats during baking. Application of extreme temperatures during baking, which caused carbonization of the outer layer of products, yielded an insignificant increase in the amount of trans isomers. As with baking, stir frying did not result in significant isomerization of the fatty acids, even when the oil was heated to 275o C and smoking heavily before the food was placed in it. Irrespective of the cooking procedure, linolenic acid was the most prone to isomerization with the highest amount of trans isomers formation. CONCLUSIONS: Baking and stir-frying at normal and/or extreme temperatures do not significantly affect the amounts of trans fats. Likewise, heating oil to the smoking point during stir-frying may decrease the amount of polyunsaturated fatty acids because of oxidative degradation. PMID- 22668847 TI - Effects of amygdala lesions on male mouse ultrasonic vocalizations and copulatory behaviour. AB - Mice produce ultrasonic vocalizations (USVs) in several behavioural contexts. In particular, male mice articulate a long series of various sounds to females during courtship behaviour. To determine the relationships between this kind of vocal behaviour and emotion, we examined the lesion effects of the amygdala, an important neural module in emotional behaviour, on USVs. We recorded USVs from mice in the lesion and the control (sham operation) groups upon presentation of females and compared USVs before and after surgery. We found that the mean syllable duration of the USVs shortened and the appearance rate of longer syllables decreased after the surgery. The main reasons for these alterations could be explained by the altered courtship behaviour. As reported previously, the mounting behaviour of the lesion group after surgery was markedly less than that of the control group. Therefore, the appearance rate of those longer syllables would decrease logically because longer syllables primarily appear during mounting and intromission. However, we can hypothesize another scenario for the alterations to vocal behaviour: effects on the direct amygdala periaqueductal grey (PAG) projection might be involved in the increase in the appearance rate of shorter syllables owing to lesion-induced loss of emotions, such as vigilance. Overall, the results suggested two possible mechanisms of the amygdala lesions on the alteration of the vocal behaviour. PMID- 22668848 TI - JNK-dependent Atg4 upregulation mediates asperphenamate derivative BBP-induced autophagy in MCF-7 cells. AB - N-Benzoyl-O-(N'-(1-benzyloxycarbonyl-4-piperidiylcarbonyl)-D-phenylalanyl)-D phenylalaninol (BBP), a novel synthesized asperphenamate derivative with the increased solubility, showed growth inhibitory effect on human breast carcinoma MCF-7 cells in a time- and concentration-dependent manner. The growth inhibitory effect of BBP was associated with induction of autophagy, which was demonstrated by the development of acidic vesicular organelles, cleavage of LC3 and upregulation of Atg4 in BBP-treated MCF-7 cells. Since the application of Atg4 siRNA totally blocked the cleavage of LC3, we demonstrated a central role of Atg4 in BBP-induced autophagy. The further studies showed that BBP increased the levels of reactive oxygen species (ROS), and pretreatment with NAC effectively blocked the accumulation of ROS, autophagy and growth inhibition triggered by BBP. Moreover, BBP induced the activation of JNK, and JNK inhibitor SP600125 reversed autophagy, the increase of Atg4 levels, conversion of LC3 and growth inhibition induced by BBP. Knockdown of JNK by siRNA efficiently inhibited ROS production and autophagy, but antioxidant NAC failed to block JNK activation induced by BBP, indicating that JNK activation may be a upstream signaling of ROS and should be a core component in BBP-induced autophagic signaling pathway. These results suggest that BBP produces its growth inhibitory effect through induction of the autophagic cell death in MCF-7 cells, which is modulated by a JNK dependent Atg4 upregulation involving ROS production. PMID- 22668849 TI - Training curriculum and simulator training for the whole surgical team: what do nurse assistants think? PMID- 22668850 TI - GFI1 and GFI1B control the loss of endothelial identity of hemogenic endothelium during hematopoietic commitment. AB - Recent studies have established that during embryonic development, hematopoietic progenitors and stem cells are generated from hemogenic endothelium precursors through a process termed endothelial to hematopoietic transition (EHT). The transcription factor RUNX1 is essential for this process, but its main downstream effectors remain largely unknown. Here, we report the identification of Gfi1 and Gfi1b as direct targets of RUNX1 and critical regulators of EHT. GFI1 and GFI1B are able to trigger, in the absence of RUNX1, the down-regulation of endothelial markers and the formation of round cells, a morphologic change characteristic of EHT. Conversely, blood progenitors in Gfi1- and Gfi1b-deficient embryos maintain the expression of endothelial genes. Moreover, those cells are not released from the yolk sac and disseminated into embryonic tissues. Taken together, our findings demonstrate a critical and specific role of the GFI1 transcription factors in the first steps of the process leading to the generation of hematopoietic progenitors from hemogenic endothelium. PMID- 22668851 TI - Hedgehog signaling via a calcitonin receptor-like receptor can induce arterial differentiation independently of VEGF signaling in zebrafish. AB - Multiple signaling pathways control the specification of endothelial cells (ECs) to become arteries or veins during vertebrate embryogenesis. Current models propose that a cascade of Hedgehog (Hh), vascular endothelial growth factor (VEGF), and Notch signaling acts instructively on ECs to control the choice between arterial or venous fate. Differences in the phenotypes induced by Hh, VEGF, or Notch inhibition suggest that not all of the effects of Hh on arteriovenous specification are mediated by VEGF. We establish that full derepression of the Hh pathway in ptc1;ptc2 mutants converts the posterior cardinal vein into a second arterial vessel that manifests intact arterial gene expression, intersegmental vessel sprouting, and HSC gene expression. Importantly, although VEGF was thought to be absolutely essential for arterial fates, we find that normal and ectopic arterial differentiation can occur without VEGF signaling in ptc1;ptc2 mutants. Furthermore, Hh is able to bypass VEGF to induce arterial differentiation in ECs via the calcitonin receptor-like receptor, thus revealing a surprising complexity in the interplay between Hh and VEGF signaling during arteriovenous specification. Finally, our experiments establish a dual function of Hh during induction of runx1(+) HSCs. PMID- 22668852 TI - Do African American women require fewer calories to maintain weight?: Results from a controlled feeding trial. AB - BACKGROUND: The high prevalence of obesity in African American (AA) women may result, in part, from a lower resting metabolic rate (RMR) than non-AA women. If true, AA women should require fewer calories than non-AA women to maintain weight. Our objective was to determine in the setting of a controlled feeding study, if AA women required fewer calories than non-AA women to maintain weight. MATERIALS AND METHODS: This analysis includes 206 women (73% AA), aged 22-75 years, who participated in the Dietary Approaches to Stop Hypertension (DASH) trial-a multicenter, randomized, controlled, feeding study comparing the effects of 3 dietary patterns on blood pressure in individuals with prehypertension or stage 1 hypertension. After a 3-week run-in, participants were randomized to 1 of 3 dietary patterns for 8 weeks. Calorie intake was adjusted during feeding to maintain stable weight. The primary outcome of this analysis was average daily calorie (kcal) intake during feeding. RESULTS: AA women had higher baseline weight and body mass index than non-AA women (78.4 vs 72.4 kg, P < .01; 29.0 vs 27.6 kg/m(2), P < .05, respectively). During intervention feeding, mean (SD) kcal was 2168 (293) in AA women and 2073 (284) in non-AA women. Mean intake was 94.7 kcal higher in AA women than in non-AA women (P < .05). After adjustment for potential confounders, there was no difference in caloric intake between AA and non-AA women (Delta = -2.8 kcal, P = .95). CONCLUSION: These results do not support the view that AA women are at greater risk for obesity because they require fewer calories to maintain weight. PMID- 22668853 TI - Handheld calorimeter is a valid instrument to quantify resting energy expenditure in hospitalized cirrhotic patients: a prospective study. AB - BACKGROUND: Nutrition management of cirrhosis in hospitalized patients is overlooked despite the clinical significance of sarcopenia or loss of muscle mass in cirrhosis. Determining optimal nutrition requirement needs precise measurement of resting energy expenditure (REE) in the cirrhotic patient. Predictive equations are not accurate, and the metabolic cart is expensive and cumbersome. The authors therefore performed a prospective study to examine the feasibility and accuracy of a handheld respiratory calorimeter (HHRC) in quantifying the REE in hospitalized cirrhotic patients not in the intensive care unit. MATERIALS AND METHODS: The study was done in 2 phases: in the first phase, the REE of 24 consecutive healthy volunteers was measured using an HHRC in different positions. The objective of this phase was to identify the impact of body and arm position on measured REE. Subsequently, in the second phase of the study, REE was measured using the HHRC and the metabolic cart in 25 consecutive well-characterized, hospitalized cirrhotic patients. The degree of concordance was calculated. RESULTS: Body position and arm position did not significantly affect the measured REE using HHRC. In patients with cirrhosis, the mean measured REE (kcal/d) using the HHRC was 1453.2 +/- 319.3 in the hospital room, 1525.6 +/- 305.2 in a quiet environment, and 1553.7 +/- 270.6 with the metabolic cart (P > .1). Predicted REE using 2 widely used equations did not correlate either with each other or with the measured REE. CONCLUSIONS: HHRC is a valid, feasible, and rapid method to determine optimal caloric needs in hospitalized cirrhotic patients. PMID- 22668854 TI - Differential orexin/hypocretin expression in addiction-prone and -resistant rats selectively bred for high (HiS) and low (LoS) saccharin intake. AB - Rats that have been selectively bred for high (HiS) saccharin intake demonstrate elevated drug-seeking behavior in several phases of addiction compared to those bred for low (LoS) saccharin intake. HiS rats also consume greater amounts of highly palatable substances compared to LoS rats; however, little is known about the neurobiological substrates moderating the divergent behaviors found between the HiS and LoS lines. Orexins are neuropeptides that have been implicated in the conditioned cue aspects of drug abuse and overconsumption of palatable substances, and differential orexin activity in the HiS and LoS phenotypes may enhance our understanding of the close relationship between food and drug reward, and ultimately food and drug addiction. The lateral hypothalamus (LH) and perifornical area (PFA) are brain regions that have been implicated in regulating feeding behavior and addiction processes, and they contain orexinergic neurons that project broadly throughout the brain. Thus, we investigated orexin and c-Fos expression in the LH and PFA using immunohistochemistry in HiS and LoS rats following either control or cocaine (15 mg/kg) injections. Results indicated that HiS rats have higher orexin-positive cell counts compared to LoS rats in both the LH and PFA, regardless of cocaine (vs. saline) treatment. In contrast, neuronal activity indicated by c-Fos expression did not differ in either of these brain areas in HiS vs. LoS rats. These results suggest that the orexin system may be involved in aspects of genetically-mediated differences in vulnerability to compulsive, reward-driven behaviors. PMID- 22668855 TI - Promazine and chlorpromazine for prolonged spinal anesthesia in rats. AB - Though promazine and chlorpromazine elicited cutaneous anesthesia, no study of spinal anesthesia with chlorpromazine and promazine has been reported. This study was to examine whether chlorpromazine and promazine produce spinal anesthesia. Using a rat model via intrathecal injection, we tested spinal blockades of motor function and nociception by promazine, chlorpromazine or bupivacaine, and so were dose-response studies and durations. We demonstrated that chlorpromazine and promazine elicited dose-dependent spinal blockades in motor function and nociception. On the 50% effective dose (ED(50)) basis, the rank of potency of these drugs was bupivacaine>promazine>chlorpromazine (P<0.05 for the differences). On an equipotent basis (25% effective dose [ED(25)], ED(50), and ED(75)), the block duration caused by chlorpromazine or promazine was longer than that caused by the long-lasting local anesthetic bupivacaine (P<0.01 for the differences). Chlorpromazine and promazine, as well as bupivacaine, showed longer duration of sensory block than that of motor block. Our data reported that intrathecal promazine and chlorpromazine with a more sensory-selective action over motor blockade had less potent and longer-lasting spinal blockades when compared with bupivacaine. PMID- 22668856 TI - Prenatal dexamethasone selectively decreases calretinin expression in the adult female lateral amygdala. AB - Exposure to high levels of glucocorticoids (GCs) during early development results in lasting disturbances in emotional behavior in rodents. Inhibitory GABAergic neurons, classified by their expression of calcium binding proteins (CBPs), also contribute to stress-related behaviors and may be GC sensitive during development. Therefore, in the present study we investigated the effects of prenatal treatment with the glucocorticoid receptor agonist dexamethasone (DEX) on expression of calbindin and calretinin in brain areas critical to emotional regulation (basolateral/lateral amygdala and hippocampal CA1 and CA3 regions). Late gestational treatment with DEX (gestational days 18-22) significantly decreased the density of calretinin immunoreactive cells in the lateral amygdala of adult female offspring with no differences in the basolateral amygdala, hippocampal CA1, or CA3 regions. Moreover, there were no effects of gestational DEX treatment on calretinin expression in males. Calbindin expression in adulthood was unaltered within either amygdala or hippocampal subregion of either sex following prenatal DEX treatment. Together these findings indicate that late gestational DEX treatment causes a targeted reduction of calretinin within the lateral amygdala of females and this may be one mechanism through which developmental glucocorticoid exposure contributes to lasting alterations in emotional behavior. PMID- 22668857 TI - Remembering the past with slow breathing associated with activity in the parahippocampus and amygdala. AB - Breathing plays an important role in perception of odors and the experience of emotions. We used the dipole tracing method to analyze brain areas related to odor-induced autobiographical memory and emotions estimated from averaged electroencephalograms triggered by inspiration onset during odor presentation. Odor stimuli were perfumes subjects named that elicited a specific, pleasant and personal memory as well as two pleasant odors for controls. The perfumes induced specific emotional responses during memory retrieval, arousal level of the memory, feelings of pleasantness and a sense of familiarity with the odor. Respiration measurement indicated that tidal volume increased and respiratory frequency decreased during presentation of perfume stimuli, showing a deep and slow breathing pattern. Throughout the olfactory stimulation, electroencephalograms and respiration were simultaneously recorded. In the averaged potentials, low frequency oscillation was phase-locked to inspiration. Dipole analysis showed that perfumes activated more widespread areas of the right parahippocampal cortex and converged in the right amygdala compared to control odors. Slow breathing synchronized with odor-induced autobiographical memory and emotions may be subconsciously stored in the parahippocampal cortex and amygdala. PMID- 22668858 TI - Association of MTHFR C677T polymorphism with loneliness but not depression in cognitively normal elderly males. AB - Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is involved in folate and homocysteine metabolism, and has been associated with geriatric disorders, including dementia and late-life depression. The present work aimed to investigate the effect of MTHFR C677T polymorphism on the presence of depression and loneliness in cognitively normal male subjects. A total of 323 cognitively normal male subjects were included in this study (mean age=80.6; SD=5.3). Depression was assessed by the Geriatric Depression Scale-Short Form (GDS-SF) and loneliness by UCLA loneliness scales. Analysis of variance (ANOVA) was used to test the between MTHFR genotype difference in depression and loneliness. Multiple regression was used to test the effect of MTHFR polymorphism on the loneliness, controlling for age, education, cognitive function, and depression. ANOVA showed a significant between-genotype difference in loneliness scores (P=0.015), and post hoc comparisons showed that subjects with C/C genotype had significantly higher loneliness ratings, compared to those with C/T or T/T genotype. Regression analysis indicated that the effect of MTHFR polymorphism on loneliness was independent of age, education, cognitive function, and depression. Our findings suggest that MTHFR C677T polymorphism may be linked more to loneliness than depression in the cognitively normal elderly males, and may be implicated in the pathophysiology of late-life depression in relation to MTHFR genes. PMID- 22668859 TI - Characterization of a novel IMP-28 metallo-beta-lactamase from a Spanish Klebsiella oxytoca clinical isolate. AB - An isolate of Klebsiella oxytoca carrying a novel IMP metallo-beta-lactamase was discovered in Madrid, Spain. The bla(IMP-28) gene is part of a chromosomally located class I integron. The IMP-28 k(cat)/K(m) values for ampicillin, ceftazidime, and cefepime and, to a lesser extent, imipenem and meropenem, are clearly lower than those of IMP-1. The His306Gln mutation may induce important modifications of the L3 loop and thus of substrate accessibility and hydrolysis and be the main reason for this behavior. PMID- 22668860 TI - CMY-2-producing Escherichia coli in the nose of pigs. PMID- 22668861 TI - Variations of AbaR4-type resistance islands in Acinetobacter baumannii isolates from South Korea. AB - AbaR resistance islands in Acinetobacter baumannii isolates from South Korea were investigated. AbaR4-type resistance islands, including bla(OXA-23)-containing Tn2006, interrupted the comM gene in A. baumannii ST75 isolates. However, Tn2006 was not identified within AbaR resistance islands of ST138 isolates, although the bla(OXA-23) gene was detected in them. The similar structures of resistance islands suggest that most carbapenem-resistant A. baumannii isolates in South Korea have originated from the same ancestor with a globally disseminated clone, GC II. PMID- 22668862 TI - From ashes to ashes: time for cigarettes to hit the dust. PMID- 22668863 TI - Smoking, atherothrombosis and clopidogrel. PMID- 22668864 TI - Does inflammation trigger fibrosis in hypertrophic cardiomyopathy: a burning question? PMID- 22668865 TI - Human cytomegalovirus neutralising antibodies and increased risk of coronary artery disease in Indian population. AB - BACKGROUND: Several studies have reported a conflicting association between cytomegalovirus (CMV) infection and coronary artery disease (CAD) based on the levels of total anti-CMV antibodies. However, none have estimated the levels of specific neutralising antibodies (NA) to CMV, which may be clinically more relevant. OBJECTIVE: To determine whether CMV-NA titres show a better association with CAD compared with total anti-CMV antibody levels. DESIGN: CMV-NA titres were measured by micro-neutralisation assay and anti-CMV IgG antibodies using ELISA in 391 consecutive CAD patients compared with the same number of controls (N=782), and 91 patients reporting recurrent cardiac events during a 4-year follow-up compared with those without a recurrent event (N=182). Levels of inflammatory markers, interleukin 6, high-sensitivity C reactive protein, fibrinogen and secretory phospholipase A2 (sPLA2), were measured by ELISA. Analysis of variance and logistic regression were used for statistical analyses. RESULTS: High CMV-NA titres showed a positive association with CAD occurrence (OR 2.24, 95% CI 1.31 to 3.85, p=0.003) and recurrent cardiac events in CAD patients (OR 4.65, 95% CI 1.21 to 17.86, p=0.025) compared with total CMV antibodies (OR 1.67, 95% CI 1.04 to 2.69, p=0.034, and 2.70, 1.04 to 7.02, p=0.040, respectively). Patients with higher quartile of CMV-NA titres and sPLA2 levels had an adjusted OR of 7.82 (95% CI 1.87 to 32.65, 0.005) for recurrent cardiac events compared with those with the lowest quartiles for both markers. CONCLUSION: These findings suggest that high CMV-NA titres in combination with inflammatory markers improve prediction of cardiac events in the Asian Indian population. PMID- 22668866 TI - Calcification of the abdominal aorta as an independent predictor of cardiovascular events: a meta-analysis. AB - CONTEXT: Abdominal aortic calcification (AAC) is a common finding in patients with atherosclerosis. OBJECTIVE: The aim of this study was to demonstrate the incremental value of AAC in predicting long term cardiovascular (CV) outcome by conducting a meta-analysis of observational studies. DATA SOURCES: MEDLINE and Cochrane databases. STUDY SELECTION: Longitudinal studies with at least 2 years of follow-up, reporting the influence of AAC on CV outcome of general population patients. DATA EXTRACTION: Four separate end points-coronary events, cerebrovascular events, all CV events and CV related death-were tested for their relationship with AAC at baseline, using weighted random effects meta-analysis. Heterogeneity was calculated using Q and I(2) statistic tests. Publication bias was assessed by funnel plot symmetry and trim and fill methods. The importance of calcium quantification was also explored (sensitivity analysis). RESULTS: 10 studies were included. An increased relative risk (RR) was found for all end points: for coronary events (five studies, n=11250) 1.81 (95% CI 1.54 to 2.14); for cerebrovascular events (four studies, n=9736) 1.37 (1.22 to 3.54); for all CV events (four studies, n=4960) 1.64 (1.24 to 2.17); and for CV death (three studies, n=4986) 1.72 (1.03 to 2.86). Analysis of studies presenting results in categories (no/minimal, moderate and severe calcification) revealed a stepwise increase in the RR for all end points. Significant heterogeneity was found in the included studies. Sources of heterogeneity were identified in the publication date, duration of follow-up, and mean age and gender differences in the included patient cohorts. CONCLUSION: Existing data suggest that AAC is a strong predictor of CV related events or death in the general population. The predictive impact is greater in more calcified aortas. The generalisability of the meta-analysis is limited by heterogeneity in the coronary events, all CV events and CV death end points. PMID- 22668867 TI - Effect of smoke-free legislation on the incidence of sudden circulatory arrest in the Netherlands. AB - OBJECTIVE: To investigate whether smoke-free legislation in the Netherlands led to a decreased incidence of out-of-hospital sudden circulatory arrest (SCA). Smoke-free legislation was implemented in two phases: a workplace ban in 2004 and an extension of this ban to the hospitality sector on 1 July 2008. DESIGN: Weekly incidence data on SCA were obtained from the ambulance registry of South Limburg, the Netherlands. Three time periods were distinguished: the pre-ban period (1 January 2002-1 January 2004), the first post-ban period (1 January 2004-1 July 2008) and the second post-ban period (1 July 2008-1 May 2010). Trends in absolute SCA incidence were analysed using Poisson regression, adjusted for population size, ambient temperature, air pollution and influenza rates. RESULTS: A total of 2305 SCA cases were observed (mean weekly incidence 5.3+/-2.3 SD). The adjusted Poisson regression model showed a small but significant increase in SCA incidence during the pre-ban period (+0.20% cases per week, p=0.044). This trend changed significantly after implementation of the first ban (with -0.24% cases per week, p=0.043), translating into a 6.8% (22 cases) reduction in the number of SCA cases after 1 year of smoke-free legislation. No further decrease was seen after the second smoking ban. CONCLUSIONS: After introduction of a nationwide workplace smoking ban in 2004, a significant decrease in the incidence of out-of-hospital SCA was seen in South Limburg. Poor enforcement of the 2008 hospitality sector ban may account for the fact that no further decrease in the incidence of SCA was seen at this time. PMID- 22668868 TI - Bicuspid aortic valve and associated aortic dilation in the young. AB - BACKGROUND: The aorta in patients with bicuspid aortic valve (BAV) is larger and grows more rapidly than in patients with tricommissural aortic valve. Young patients with BAV can have significant aortic dilation that places them at risk for morbidity and mortality. OBJECTIVE: The aims of this study were to determine the rate of growth of the aorta in young patients with BAV and to identify predictors of significant dilation and rapid aortic growth. METHODS: 333 patients were randomly selected from an inception cohort of 1192 patients with BAV identified between 1986 and 1999. RESULTS: Median age at the most recent study was 13.5 (0-30) years, 74% were male. Moderate/severe (Z>4) aortic root and ascending aortic dilation was present in 14/333 (5%) and 53/333 (16%) of patients, respectively. In longitudinal follow-up, only a minimal change in aortic Z-score was noted. Predictors of moderate/severe aortic root dilation included moderate/severe aortic regurgitation, absence of moderate/severe aortic stenosis and fusion of the right and left coronary leaflets. Predictors of moderate/severe ascending aortic dilation included moderate/severe aortic regurgitation and absence of aortic coarctation. CONCLUSION: Moderate/severe dilation of the ascending aorta is common in young patients with BAV, but moderate/severe dilation of the aortic root is less common. The Z-scores for both remained relatively constant over time even in patients with significant dilation, implying that young children with moderate/severe aortic dilation may be at the highest risk for dilation-related complications as adults. PMID- 22668869 TI - Angina pectoris in patients with normal coronary angiograms: current pathophysiological concepts and therapeutic options. PMID- 22668870 TI - Bibliography--Editors' selection of current world literature. PMID- 22668871 TI - Role of CSN5/JAB1 in Wnt/beta-catenin activation in colorectal cancer cells. AB - CSN5/JAB1 is a critical subunit of the COP9 signalosome (CSN) and is overexpressed in many human cancers, but little is known about the role of CSN5 in colorectal cancer (CRC). To explore the functional role of CSN5 in colorectal tumorigenesis, we applied siRNA technology to silence CSN5 in HeLa, SW480, HCT116, HT29, and CaCo2 cells. CSN5 knock-down led to reduced beta-catenin and phospho-bcatenin levels and this was paralleled by reduced CRC cell proliferation and reduced apoptosis rates, whereas the short-term beta-catenin protein stability was enhanced by CSN5 knock-down in SW480 cells. Together, these data implicate the CSN in the pathogenesis of CRC via regulation of the Wnt/beta catenin pathway PMID- 22668872 TI - QuickView in small-bowel capsule endoscopy is useful in certain clinical settings, but QuickView with Blue Mode is of no additional benefit. AB - BACKGROUND: Analysis of small-bowel capsule endoscopy (SBCE) is time-consuming. QuickView (QV) has been added to the RAPID software to reduce the reading times. However, its validity is still under intense review. Recently, we have shown that Blue Mode (BM) provides improvements in images for most lesion categories. AIM: To assess the validity of QuickView with white light (QVWL) and QuickView with Blue Mode (QVBM) reading, in a group of patients who underwent SBCE in our centre, by comparing it with the standard video sequence review (used as reference) by experienced SBCE readers. METHODS: This was a retrospective study; all SBCE (August 2008-November 2011), performed with PillCam SB, with complete small-bowel visualization were included. A clinician with previous SBCE experience, unaware of the SBCE reports, reviewed prospectively the video streams on RAPID platform using QVWL and QVBM. All SBCE had been reported previously using the standard mode; these reports were considered as the reference. There were 106 cases of obscure gastrointestinal bleeding (OGIB), 81 cases of known or suspected Crohn's disease (CD) and 10 cases of polyposis syndromes. RESULTS: The mean small-bowel evaluation was 475 (+/- 270) s and 450 (+/- 156) s for QVWL and QVBM, respectively. In the OGIB (n=106; 21 overt/85 occult), with QVWL, 54 [P0 (28), P1 (18), P2 (8)] lesions were detected, 63 [P0 (48), P1 (13), P2 (2)] with QVBM, as compared with 98 [P0 (67), P1 (23), P2 (8)] by standard (reference) reporting. For P1+P2 lesions, the sensitivity, specificity, positive predictive value and negative predictive value for QVWL (as compared with reference reporting) were 92.3, 96.3, 96 and 92.8%, respectively. For QVBM, the above values were 91, 96, 96.2 and 90.6%, respectively. Eighty-one (n=81) patients underwent SBCE for small-bowel evaluation on the basis of a clinical history of suspected or known CD. With QVWL, 71 mucosal ulcers were detected, 68 with QVBM, as compared with 155 mucosal ulcers with reference reading. Finally, in the polyposis category with QVWL and QVBM, four polypoid lesions were detected compared with seven with standard (reference) review. CONCLUSION: QV can be used confidently in OGIB in an urgent inpatient setting and in outpatients with occult OGIB or suspected CD. Furthermore, BM does not confer any additional advantage in the QV setting. Standard review settings should be used in all other cases. PMID- 22668873 TI - Risk of development of acute pancreatitis with pre-existing diabetes: a meta analysis. AB - OBJECTIVES: It is well established that acute pancreatitis (AP) often causes diabetes mellitus. However, whether pre-existing diabetes is associated with the development of AP remains unknown. To clarify the association of pre-existing diabetes and the development of AP, we carried out a meta-analysis of observational studies. METHODS: A computerized literature search was performed in MEDLINE (from 1 January 1966) and EMBASE (from 1 January 1974), through 31 January 2012. We also searched the reference lists of relevant articles. Summary relative risks with their corresponding 95% confidence intervals (CIs) were calculated using a random-effects model. Between-study heterogeneity was assessed using Cochran's Q statistic and the I 2. RESULTS: A total of seven articles (10 523 incident cases of AP) were included in this meta-analysis. Analysis of seven studies indicated that, compared with nondiabetic individuals, diabetic individuals had a 92% increased risk of development of AP (95% CI 1.50-2.47). There was significant evidence of heterogeneity among these studies (P heterogeneity<0.001, I 2=93.0%). These increased risks were independent of alcohol use, gallstones, and hyperlipidemia. CONCLUSION: Although the current evidence supports a positive link between pre-existing diabetes and an increased risk of development of AP, additional studies, with a perfect design, are required before definitive conclusions can be drawn. PMID- 22668874 TI - Tolerance of liver biopsy in a tertiary care center: comparison of the percutaneous and the transvenous route in 143 prospectively followed patients. AB - BACKGROUND: Transjugular liver biopsy (TJLB) is usually performed when a percutaneous liver biopsy (PLB) is contraindicated. TJLB is an invasive procedure and the patient's tolerance may be variable. AIM: To compare patient tolerance and quality of the biopsy sample between PLB and TJLB. PATIENTS AND METHODS: A total of 143 patients underwent a liver biopsy; of these, 75 underwent TJLB and 68 underwent PLB. To evaluate patient tolerance, we used a visual analog scale that scored the intensity of the symptoms. The length of the biopsy sample and the total number of portal tracts per biopsy were also determined for assessment of biopsy quality. RESULTS: The biopsy sample length was similar in both groups (18.88 +/- 8.83 mm on PLB vs. 18.26 +/- 10.30 mm on TJLB). No differences were found in the number of portal tracts between the two groups (10.43 +/- 8.25 on TJLB vs. 12 +/- 10.09 on PLB). Fewer complications were observed in the TJLB group compared with the PLB group (P=0.002).Further, higher degree of pain was reported by patients who underwent PLB compared with patients who underwent TJLB (3.18 +/- 3.17 vs. 1.19 +/- 2.07); as such, there was a greater need for analgesics on PLB. CONCLUSION: TJLB and PLB techniques provide similar quality of tissue samples; however, TJLB is less painful and therefore better tolerated by patients. PMID- 22668875 TI - Metabolic syndrome and nonalcoholic fatty liver disease in a Spanish population: influence of the diagnostic criteria used. AB - OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is highly prevalent and it is considered the hepatic component of the metabolic syndrome (MetS). The WHO, the National Cholesterol Education Program (NCEP) and the International Diabetes Federation (IDF) have different criteria to define MetS. The aim of this study was to analyze the association between NAFLD and MetS using the three existing criteria. METHODS: Cross-sectional, descriptive population-based study derived from a previous study on the prevalence and factors associated with NAFLD in Spain. RESULTS: A total of 696 individuals [mean age 53 +/- 14 years (range 17-83 years)] were included, 59% of whom were women. The prevalence of MetS was 34.2% according to the IDF, 17.7% according to the NCEP and 15.5% according to the WHO. Concordance among the different criteria was between 76 and 87%, with kappa indexes between 0.39 and 0.54. NAFLD was present in 184 individuals according to echographic criteria (prevalence 26.4%). The prevalence of NAFLD among patients with MetS was 43% (IDF), 53% (NCEP) and 64% (WHO). The odds ratio (95% confidence interval) for a logistic regression using NAFLD as a dependent variable varied from 3.44 (2.42-4.88) for IDF to 7.28 (4.68-11.3) for WHO, being 4.28 (2.84-6.43) for NCEP. CONCLUSION: The MetS is quite frequent in the general population, although its prevalence varies considerably according to the criteria used for its definition. The MetS is associated with NAFLD, with the WHO definition being the best to determine its presence, probably because of the inclusion of insulin resistance as a main component. Unification of criteria is needed to adequately compare the prevalence of MetS and its relationship with NAFLD in different population groups. PMID- 22668876 TI - Long-term follow-up of hepatitis B e antigen-negative patients treated with peginterferon alpha-2a: progressive decrease in hepatitis B surface antigen in responders. AB - OBJECTIVE: Peginterferon (PEG-IFN) is considered as a first-line treatment option for hepatitis B e antigen (HBeAg)-negative chronic hepatitis B. We aimed to evaluate the long-term response to PEG-IFN in HBeAg-negative patients. METHODS: All patients enrolled in the PARC study who completed the treatment phase were eligible for this long-term follow-up (LTFU) study. Patients received PEG-IFN alpha-2a (180 MUg weekly) +/- ribavirin (1000-1200 mg daily) for 48 weeks and had at least one additional LTFU visit after the initial follow-up period of 24 weeks (mean duration 2.1 +/- 0.2 years). Retreated patients were considered nonresponders. RESULTS: Of 117 patients who completed the treatment phase, 79 (68%) were included in this LTFU study. Among 19 patients with a combined response at 24 weeks after treatment [initial responders; hepatitis B virus DNA<10 000 copies/ml (<1714 IU/ml) and normal alanine aminotransferase], 12 (63%) sustained this response through LTFU. Three additional patients showed such a response at LTFU, resulting in a total of 15 (19%) combined responders at LTFU. A marked decrease in the serum hepatitis B surface antigen (HBsAg) levels was observed in initial responders, resulting in HBsAg clearance in 26% of the patients (6% of all LTFU participants). CONCLUSION: About one-third of HBeAg negative patients with a response to PEG-IFN at 24 weeks after treatment subsequently had a relapse during 2 years of follow-up. Despite the limited overall efficacy of PEG-IFN, patients responding to PEG-IFN treatment showed a marked decrease in serum HBsAg, resulting in a high rate of HBsAg clearance, which indicates the need for predictors of response to PEG-IFN in HBeAg-negative disease. PMID- 22668877 TI - Twist1 causes the transcriptional repression of claudin-4 with prognostic significance in esophageal cancer. AB - Twist1 is a transcription factor that is involved in epithelial-mesenchymal transition by suppressing intercellular adhesion. In this study, we aimed to determine the role of Twist1 in the regulation of claudin-4 expression and investigate its specific mechanisms and clinical implications using human esophageal carcinoma cell lines and tissues. As a result, up-regulation of Twist1 decreased both gene and protein expression levels of endogenous claudin-4 and the suppression was mediated by direct binding of Twist1 to the canonical E-box in the promoter region of claudin-4. In addition, there was a significant inverse correlation of claudin-4 with Twist1 in esophageal cancer tissues. High Twist1 and low claudin-4 expression was associated with the poorest prognosis and was more highly correlated with adverse outcome than any other subgroup with statistical significance (p=0.001). Our results indicate that Twist1 induces the repression of claudin-4 expression during the epithelial-mesenchymal transition in esophageal carcinoma. PMID- 22668879 TI - Origins of "us" versus "them": prelinguistic infants prefer similar others. AB - A central feature of human psychology is our pervasive tendency to divide the social world into "us" and "them". We prefer to associate with those who are similar to us over those who are different, preferentially allocate resources to similar others, and hold more positive beliefs about similar others. Here we investigate the developmental origins of these biases, asking if preference for similar others occurs prior to language and extensive exposure to cultural norms. We demonstrate that, like adults, prelinguistic infants prefer those who share even trivial similarities with themselves, and these preferences appear to reflect a cognitive comparison process ("like me"/"not like me"). However, unlike adults, infants do not appear to prefer others with an utterly arbitrary similarity to themselves. Together, these findings suggest that the phenomena of ingroup bias, and enhanced interpersonal attraction toward those who resemble ourselves, may be rooted in an inherent preference for similarity to self, which itself may be enhanced during development by the influence of cultural values. PMID- 22668878 TI - Dis3- and exosome subunit-responsive 3' mRNA instability elements. AB - Eukaryotic RNA turnover is regulated in part by the exosome, a nuclear and cytoplasmic complex of ribonucleases (RNases) and RNA-binding proteins. The major RNase of the complex is thought to be Dis3, a multi-functional 3'-5' exoribonuclease and endoribonuclease. Although it is known that Dis3 and core exosome subunits are recruited to transcriptionally active genes and to messenger RNA (mRNA) substrates, this recruitment is thought to occur indirectly. We sought to discover cis-acting elements that recruit Dis3 or other exosome subunits. Using a bioinformatic tool called RNA SCOPE to screen the 3' untranslated regions of up-regulated transcripts from our published Dis3 depletion-derived transcriptomic data set, we identified several motifs as candidate instability elements. Secondary screening using a luciferase reporter system revealed that one cassette-harboring four elements-destabilized the reporter transcript. RNAi based depletion of Dis3, Rrp6, Rrp4, Rrp40, or Rrp46 diminished the efficacy of cassette-mediated destabilization. Truncation analysis of the cassette showed that two exosome subunit-sensitive elements (ESSEs) destabilized the reporter. Point-directed mutagenesis of ESSE abrogated the destabilization effect. An examination of the transcriptomic data from exosome subunit depletion-based microarrays revealed that mRNAs with ESSEs are found in every up-regulated mRNA data set but are underrepresented or missing from the down-regulated data sets. Taken together, our findings imply a potentially novel mechanism of mRNA turnover that involves direct Dis3 and other exosome subunit recruitment to and/or regulation on mRNA substrates. PMID- 22668880 TI - Risk factors for prolonged hospitalization after gynecologic laparoscopic surgery. AB - OBJECTIVE: To determine perioperative risk factors for prolonged hospitalization after gynecologic laparoscopic surgery. METHODS: Data on patients who underwent gynecologic laparoscopic surgery at a single academic institution from January 2000 to January 2009 were evaluated. Patient demographics, clinical history, intraoperative data, and postoperative adverse events were analyzed. Logistic regression analysis identified significant predictors of prolonged hospitalization (hospital stay>48 h after surgery). A risk score was created from the analysis to predict prolonged hospitalization. RESULTS: Eight hundred seven patients were included. The median body mass index was 26.5 kg/m(2) (range, 14.2 72.3 kg/m(2)), and the median age was 49 years (range, 12-88 years). Four hundred fifty-nine patients (56.9%) underwent surgery for benign conditions, and 348 (43.1%) underwent surgery for malignant disease. A total of 78 patients (9.7%) had a prolonged hospitalization. Independent predictors of prolonged hospitalization were age>54 years (P<0.0001), operative blood loss>120 mL (P<0.0001), intraoperative or postoperative blood transfusion (P=0.0237), and early postoperative complication (P<0.0001). Having a prior laparoscopy was associated with a shorter hospital stay (P=0.0276). The risk score showed how changes in perioperative factors change the risk of prolonged hospitalization. CONCLUSION: Factors such as age, blood loss, perioperative blood transfusion, and postoperative complications are associated with prolonged length of stay after laparoscopic surgery, while having a prior laparoscopy is associated with a shorter hospital stay. A clinical scoring system can be used to estimate probability of prolonged hospitalization after gynecologic laparoscopic surgery. PMID- 22668881 TI - Changing demographics of cervical cancer in the United States (1973-2008). AB - OBJECTIVE: To describe changes in the cervical cancer population. METHODS: The SEER database 9 registries from 1973 to 2008 were queried to perform a retrospective cohort study of women with invasive cervical cancer. Estimated annual percent change (EAPC) in incidence rates and 95% confidence intervals (CI) over the entire study period were compared according to age, stage, race, and cell type (squamous [SCC] and adenocarcinoma [ACA]). Proportions and odds ratios (OR) were calculated for patients diagnosed during the second half (1990-2008) compared to first half (1973-89) of the study period. RESULTS: 40,363 women with cervical cancer were entered into SEER. The EAPC are falling fastest among those with localized disease (-2.5%; 95% CI -2.8 to -2.1), age>=50 (-3.0%; 95% CI=-3.2 to -2.8), and black women (-3.8%; 95% CI=-4.1 to -3.6). The odds of a newly diagnosed cervical cancer patient having advanced disease are 10% higher, being less than age 50 are 37% higher, and being Asian or Pacific Islander are 68% higher in the second time period as compared to the first. CONCLUSIONS: In the US, the population with cervical cancer is changing. Patients are presently significantly more likely to be pre-menopausal, Asian or Pacific Islander, and more frequently have non-squamous histology than previously. These progressive and cumulative changes could be due to the disparate impact of current population based screening and prevention strategies. Understanding the implications of these evolving population characteristics may facilitate planning targeted studies and interventions for cervical cancer prevention, screening and treatment in the future. PMID- 22668882 TI - Prognostic role of indoleamine 2,3-dioxygenase in endometrial carcinoma. AB - OBJECTIVE: Indoleamine-2,3-dioxygenase (IDO) suppresses the function of T lymphocytes and is an important immune escape mechanism for cancer. Therefore, it is to be expected that IDO influences prognosis of cancer patients. This study aimed to investigate the prognostic role of IDO expression in a large cohort of endometrial carcinoma (EC) patients. METHODS: A tissue microarray containing primary EC tissue of 355 patients treated in a single institution was used to evaluate IDO expression. Expression of IDO was associated with clinicopathological characteristics, survival and previously determined numbers of CD8(+) and Foxp3(+) T-lymphocytes. RESULTS: IDO(high) expression was associated with lower numbers of intratumoral CD8(+) T-lymphocytes (p=0.031). Next to well-known prognostic parameters, IDO(high) expression was independently associated with poor disease specific survival in the general cohort of EC patients (HR 2.62, 95% C.I. 1.48-4.66, p=0.001) and among patients with early stage EC (HR 3.06, 95% C.I. 1.10-8.54, p=0.032). CONCLUSION: Our results show that IDO expression is associated with poor survival. This provides evidence that further research into the use of IDO blocking agents in cancer treatment is valid where it might be a promising new therapeutic strategy. PMID- 22668884 TI - Metal binding properties and structure of a type III metallothionein from the metal hyperaccumulator plant Noccaea caerulescens. AB - Metallothioneins (MT) are low molecular weight proteins with cysteine-rich sequences that bind heavy metals with remarkably high affinities. Plant MTs differ from animal ones by a peculiar amino acid sequence organization consisting of two short Cys-rich terminal domains (containing from 4 to 8 Cys each) linked by a Cys free region of about 30 residues. In contrast with the current knowledge on the 3D structure of animal MTs, there is a striking lack of structural data on plant MTs. We have expressed and purified a type III MT from Noccaea caerulescens (previously Thlaspi caerulescens). This protein is able to bind a variety of cations including Cd(2+), Cu(2+), Zn(2+) and Pb(2+), with different stoichiometries as shown by mass spectrometry. The protein displays a complete absence of periodic secondary structures as measured by far-UV circular dichroism, infrared spectroscopy and hydrogen/deuterium exchange kinetics. When attached onto a BIA-ATR biosensor, no significant structural change was observed upon removing the metal ions. PMID- 22668883 TI - Maintenance of reinforcement to address the chronic nature of drug addiction. AB - BACKGROUND: Drug addiction can be a chronic problem. Abstinence reinforcement can initiate drug abstinence, but as with other treatments many patients relapse after the intervention ends. Abstinence reinforcement can be maintained to promote long-term drug abstinence, but practical means of implementing long-term abstinence reinforcement are needed. METHODS: We reviewed 8 clinical trials conducted in Baltimore, MD from 1996 through 2010 that evaluated the therapeutic workplace as a vehicle for maintaining reinforcement for the treatment of drug addiction. The therapeutic workplace uses employment-based reinforcement in which employees must provide objective evidence of drug abstinence or medication adherence to work and earn wages. RESULTS: Employment-based reinforcement can initiate (3 of 4 studies) and maintain (2 studies) cocaine abstinence in methadone patients, although relapse can occur even after long-term exposure to abstinence reinforcement (1 study). Employment-based reinforcement can also promote abstinence from alcohol in homeless alcohol dependent adults (1 study), and maintain adherence to extended-release naltrexone in opioid dependent adults (2 studies). CONCLUSION: Treatments should seek to promote life-long effects in patients. Therapeutic reinforcement may need to be maintained indefinitely to prevent relapse. Workplaces could be effective vehicles for the maintenance of therapeutic reinforcement contingencies for drug abstinence and adherence to addiction medications. PMID- 22668885 TI - Quantitative morphological magnetic resonance imaging follow-up of low-grade glioma: a plea for systematic measurement of growth rates. AB - Supratentorial hemispheric diffuse low-grade gliomas (LGGs), i.e., World Health Organization grade II gliomas, are a heterogeneous group of tumors. During their natural course, LGGs tend to progress to a higher grade of malignancy, leading to neurological disability and ultimately to death. In this review, we will show, that during their low-grade period, these tumors exhibit systematically a spontaneous and continuous radiological growth, whatever their histological subtypes. The radiological tumor growth is easily quantified by measuring the evolution of the equivalent tumor diameter (calculated from the tumor volume), obtaining the velocity of diametric expansion (VDE). The spontaneous VDE of LGGs varies markedly with an average VDE of about 4 mm/year. It depends on intrinsic factors (1p19q codeletion status, P53 overexpression status) and can be modified by extrinsic factors (pregnancy). The spontaneous VDE carries a strong prognostic significance regarding progression-free and overall survivals. As a consequence, VDE should be integrated along with the other "static" parameters (multimodal imaging, histological and molecular analyses) in the initial investigations. In addition, the assessment of VDE obtained before, during, and after a particular oncological treatment helps in analyzing their effects on LGGs on an individual basis, helping to guide the decision making. PMID- 22668886 TI - Safety and efficacy of tirofiban in stent-assisted coil embolization of intracranial aneurysms. AB - BACKGROUND: Thromboembolic complications are a major concern in stent-assisted coiling of intracranial aneurysms that may be prevented with adequate antiplatelet therapy. OBJECTIVE: To assess the safety and efficacy of tirofiban in stent-assisted coiling. METHODS: Two protocols were used. In the initial protocol, tirofiban was administered intravenously as a 0.4 MUg/kg per min bolus for 30 minutes followed by 0.10 MUg.kg min maintenance infusion. The revised protocol consisted of a 0.10 MUg.kg min maintenance infusion alone. RESULTS: Sixty-seven patients received tirofiban, 16 under the initial protocol and 51 under the revised protocol. Thirty (44.8%) patients had sustained a subarachnoid hemorrhage (SAH). Tirofiban infusion was initiated after thromboembolic events in 9 (13.4%) patients and prophylactically in 58 (86.6%). Four (6.0%) intracranial hemorrhages were noted. Three (18.8%) intracranial hemorrhages occurred with the initial protocol in patients treated electively and were fatal in 2 (66.7%) cases. The only complication (1.9%) under the revised protocol was a subclinical worsening of the computed tomographic appearance of an SAH. There was no tirofiban-related morbidity or deaths with the revised protocol. Of 9 patients that received tirofiban as a rescue treatment, 7 (77.8%) had complete and 2 (22.2%) had partial arterial recanalization. No thromboembolic events occurred in patients receiving prophylactic tirofiban. CONCLUSION: A bolus followed by a maintenance dose of tirofiban appears to have a high risk of cerebral hemorrhage. A maintenance infusion without an initial bolus, however, has an exceedingly low risk of hemorrhage and appears to be very safe and effective, even in the setting of SAH. PMID- 22668887 TI - Longitudinal analysis of visual outcomes after surgical treatment of adult craniopharyngiomas. AB - BACKGROUND: Craniopharyngiomas (CRPs) often cause visual deterioration (VD) due to the close vicinity of the optic apparatus. OBJECTIVE: To evaluate longitudinal visual outcomes after surgery of CRP and determine the prognostic factors thereof. METHODS: One hundred forty-six adult patients who underwent surgery for newly diagnosed CRP were retrospectively reviewed. There were 87 male patients (60%), and the median age was 41 years (range, 18-75). The mean follow-up duration was 88.7 months (range, 24-307). A visual impairment score was used to assess the short-term (<1 month) and long-term (>2 years) visual outcomes. RESULTS: Gross total removal was performed in 53 patients (36%), and tumor recurrence occurred in 40 patients (27%). The average preoperative, short- and long-term visual impairment scores were 44.4, 38.5, and 38.1, respectively, on a 0- to 100-point scale (with 100 indicating the worst vision). Short- and long term VD occurred in 28 (19%) and 39 patients (27%), respectively. Subtotal removal (STR) alone (P = .010; OR = 4.8), short-term VD (P < .001; OR = 39.7), and tumor recurrence (P < .001; OR = 28.2) were significant risk factors for long term VD in the multivariate analysis. Patients undergoing STR alone had higher tumor recurrence rates in comparison with those who underwent gross total removal or STR with adjuvant therapy (P < .001). CONCLUSION: Short-term VD secondary to the surgical insult and the recurrence of the tumor were strong predictors of long-term visual outcomes after surgical treatment for CRP. STR alone may be an ineffective strategy for achieving tumor control and optimal visual outcomes in patients with CRP. PMID- 22668888 TI - Extracranial-intracranial bypass for stroke-is this the end of the line or a bump in the road? AB - The results of the recently published Carotid Occlusion Surgery Study, which failed to show a benefit of extracranial-intracranial (EC-IC) bypass over medical therapy in patients with symptomatic hemodynamically significant carotid occlusion, have been interpreted by some as the end of the line for EC-IC bypass in the management of stroke. Despite being carefully conceived and executed, several aspects of the trial design, study population, and underlying assumptions deserve further examination to determine how best to translate these results into clinical practice. Although a general expansion of EC-IC bypass use in this population would not be supported by the trial results, a select subset of patients with medically refractory hemodynamic symptoms may well benefit from surgery performed with sufficiently low perioperative morbidity. The potential for beneficial functional or cognitive impact of revascularization also remains under investigation. Limited application and further study with an eye to future developments, rather than complete abandonment, is warranted. PMID- 22668889 TI - Tailored temporal lobectomy for medically intractable epilepsy: evaluation of pathology and predictors of outcome. AB - BACKGROUND: There have been only a few large series that have used a tailored temporal lobectomy. OBJECTIVE: To clarify whether tailoring a temporal lobe resection will lead to equivalent epilepsy outcomes or have the same predictive factors for success when compared with standard resections. METHODS: Retrospective analysis of 222 patients undergoing a tailored temporal lobe resection. Demographic measures and typical factors influencing outcome were evaluated. RESULTS: Pathology included 222 cases. With a mean follow-up of 5.4 years, 70% of patients achieved Engel class I outcome. A significant factor predicting Engel class I outcome on multivariate analysis was lesional pathology (P = .04). Among patients with hippocampal sclerosis, extent of lateral neocortical resection and hippocampal resection were not statistically associated with Engel class I outcome (P = .93 and P = .24). However, an analysis of Engel class subgroups a to d showed that patients who had a complete hippocampectomy in the total series were more likely to achieve an Engel class Ia outcome (P = .04). This was also true among patients with hippocampal sclerosis (P = .03). Secondarily, generalized seizure (P = .01) predicted outcome less than Engel class I. Predictive of poor outcome was the need for preoperative electrodes (P = .02). Complications included superior quadrant visual field defects, 2 cases of permanent dysphasia, and 3 wound infections. CONCLUSION: Predictors of successful seizure outcome for a tailored temporal lobectomy are similar to standard lobectomy. Patients with secondarily generalized epilepsy and cases in which preoperative subdural electrodes were thought necessary were less likely to achieve class I outcome. Among Engel class I cases, those who had a complete hippocampectomy were more likely to achieve Engel class Ia outcome. PMID- 22668891 TI - Imprisonment and torture of doctors in Bahrain. PMID- 22668890 TI - Euthanasia - no dignity in death without an ethos of respect for human life. PMID- 22668892 TI - SAMA speaks out about the victimisation of doctors in Bahrain. PMID- 22668893 TI - Legal imperatives for consent for children participating in research. PMID- 22668894 TI - Stem cell therapy and amyotrophic lateral sclerosis. PMID- 22668895 TI - Hydatid cysts of the breast and parotid gland. AB - We report 2 interesting cases of hydatid cysts in unusual sites: in the breast and the deep lobe of the parotid gland. PMID- 22668896 TI - Silicosis - 10 000 gold miners getting set to sue. AB - Tagged as victims of 'the world's biggest, longest running industrial disaster; dwarfing Chernobyl', 10 000 known silicosis-affected Southern African gold miners are finally set to negotiate a payout that could induce a painful paroxysm of shareholder coughing across the Johannesburg Stock Exchange. PMID- 22668897 TI - Ubuntu research values needed for Africa. AB - Ex Africa semper aliquid novi. Africa's health researchers last month took greater collective responsibility for cultivating their continent's historically neglected and under-funded work when an international forum in Cape Town agreed on co-operative strategies to translate their findings into improving more lives on the ground. PMID- 22668898 TI - 'Formulaic' gender-abuse guidelines seldom followed. AB - The trumpeting by the Health Professions Council (HPCSA) of screening guidelines for emergency care workers handling victims of domestic violence - while welcomed - got a muted response from emergency medicine chiefs in the country's most brutal province last month. The two people heading the Western Cape's clinical protocols and training for emergency medicine and overall emergency medicine services, had reservations as to how practical - or user-friendly - the guidelines are in high-pressure or dangerous situations encountered by their staff. PMID- 22668899 TI - Govt steps up to stop corrosion of health research. AB - Government is to fund 1 000 PhDs across health disciplines over the next decade and add clinical research centres to hospitals earmarked for revitalisation so that it can build relevant evidence-based knowledge into the public health system - and begin tackling the crisis in clinical research. PMID- 22668900 TI - Willem abraham cronje. PMID- 22668901 TI - Transplantation of the heart: An overview of 40 years' clinical and research experience at Groote Schuur Hospital and the University of Cape Town: Part II. Laboratory research experience. AB - Extensive experimental research on various aspects of heart transplantation was undertaken during the first 2 decades. An overview of this work is presented, and some still unpublished work has been included. Experimental laboratory investigation was an integral activity of the cardiac transplantation programme at the University of Cape Town over these years, and has remained so ever since. These studies provided invaluable fundamental information upon which future clinical work was based. It is therefore necessary to briefly mention and discuss this information, most of which has been published in detail by the various investigators concerned. PMID- 22668902 TI - Transplantation of the heart: An overview of 40 years' clinical and research experience at Groote Schuur Hospital and the University of Cape Town: Part I. Surgical experience and clinical studies. AB - The heart transplant programme at Groote Schuur Hospital and the University of Cape Town has continued uninterruptedly since the first human transplant in 1967. Orthotopic heart transplantation was followed by the heterotopic method in 1974, considerably improving the clinical results. In 1983, owing to the advent of cyclosporin A, the orthotopic method was once again predominantly adopted. Early graft failure for various reasons remains a major complication, and heterotopic heart transplantation is perhaps the best way to deal with it. PMID- 22668903 TI - Hospital-acquired infections - when are hospitals legally liable? AB - Hospital-acquired infections (nosocomial infections) are acquired in healthcare settings by patients admitted for reasons unrelated to the infection or not previously infected when admitted to the facility. Liability for hospital acquired infections depends on whether the hospital: (i) has introduced best practice infection control measures; (ii) has implemented best practice infection control measures; or (iii) will be vicariously liable for negligent or intentional failures by staff to comply with the infection control measures implemented. A hospital and hospital administrators may be held directly liable for not introducing or implementing best practice infection control measures, resulting in harm to patients. The hospital may also be held vicariously liable where patients have been harmed because hospital staff negligently or intentionally failed to comply with the infection control measures that have been implemented by the hospital, during the course and scope of their employment. PMID- 22668904 TI - A community officer's perspective of a rural hospital in KwaZulu-Natal. PMID- 22668905 TI - Dermatological manifestations of measles infection in hospitalised paediatric patients observed in the 2009 - 2011 Western Cape epidemic. AB - Introduction. Measles is an acute vaccine-preventable infection common in childhood. In this study, the common dermatological signs of measles were designated the 'classic dermatological measles syndrome'. Methods. We attempted to ascertain the prevalence of 'non-classic' dermatological measles presentation in 69 paediatric patients admitted to New Somerset Hospital, Western Cape, during the recent South African measles outbreak. The patients were examined and photographed, after informed consent had been obtained, and findings were assessed by 1 dermatology consultant and 6 dermatology registrars. Measles infection was confirmed in 38 of the patients by means of IgM testing. The data were analysed using Stata version 11.1 statistical software. Outcomes. Of the group, 17.4% (95% CI 8.2 - 26.6%) displayed a classic measles dermatological picture, although all had been clinically diagnosed and admitted as complicated measles cases. Those serologically confirmed to have measles (N=38), 26.3% (95% CI 11.6 - 40.9%) conformed to the classic dermatological picture. Therefore, a significant majority of these patients presented with what was considered in this study to be a 'non-classic' dermatological picture. Conclusions. Measles infection in a paediatric population requiring admission may frequently present without a full-house classic dermatological picture. Recognised signs in isolation may be of greater value than the classically described syndrome as a whole. 'Non-classic' dermatological forms may occur more frequently than anticipated in complicated cases needing admission. Skin necrosis may be associated with measles. PMID- 22668906 TI - Delay in commencing treatment for MDR TB at a specialised TB treatment centre in KwaZulu-Natal. AB - Background. According to the National Department of Health (NDoH) guidelines, patients diagnosed with MDR TB must be referred to a specialised treatment centre for initiation of effective therapy. MDR TB is difficult to diagnose and the centralised referral model is beset with challenges that contribute to treatment delays, increased patient morbidity and mortality, and MDR TB nosocomial transmission. Culture and DST takes 8 weeks or longer to obtain results while line probe assays (LPAs) can give a result in hours. LPAs and the GeneXpert MTB/Rif (GX) are ground-breaking discoveries for TB diagnosis. However, they are not easily accessible or available to those needing it, so culture and sensitivity testing remains the gold standard for diagnosis. Aim. This study aimed to assess the delay in the initiation of MDR TB treatment and profiled the patients being referred to a specialised drug-resistant treatment centre in KwaZulu-Natal. Results. Of all the patients, 75% referred showed a mean delay of 12.4 weeks from the date of sputum collection for culture and drug sensitivity testing to the start of treatment. Most of the patients were symptomatic for TB and HIV-positive. Discussion. Our findings suggest that current policy on the initiation of effective treatment needs urgent revision. Staff should be appropriately trained in LPA and GX technology to reduce delays in initiating treatment for MDR TB. The NDoH's plans for rapid diagnosis and reducing the treatment burden on centralised MDR TB management facilities are in the early phases of implementation and will take years to achieve favourable and significant outcomes. Conclusion. There is a significant delay in initiating definitive management for MDR TB. PMID- 22668907 TI - Aminoglycoside-induced hearing loss in HIV-positive and HIV-negative multidrug resistant tuberculosis patients. AB - Background. Ototoxicity following aminoglycoside treatment for multidrug resistant tuberculosis (MDR-TB) is a significant problem. This study documents the incidence of ototoxicity in HIV-positive and HIV-negative patients with MDR TB and presents clinical guidelines relating to ototoxicity. Methods. A prospective cohort study of 153 MDR-TB patients with normal hearing and middle ear status at baseline controlling for 6 mitochondrial mutations associated with aminoglycoside-related ototoxicity, at Brooklyn Chest Hospital in Cape Town. Pure tone audiometry was performed monthly for 3 months to determine hearing loss. HIV status was recorded, as was the presence of 6 mutations in the MT-RNR1 gene. Results. Fifty-seven per cent developed high-frequency hearing loss. HIV-positive patients (70%) were more likely to develop hearing loss than HIV-negative patients (42%). Of 115 patients who were genetically screened, none had MT-RNR1 mutations. Conclusion. Ototoxic hearing loss is common in MDR-TB patients treated with aminoglycosides. HIV-positive patients are at increased risk of ototoxicity. Auditory monitoring and auditory rehabilitation should be an integral part of the package of care of MDR-TB patients. PMID- 22668908 TI - Fresh-frozen plasma use in a South African tertiary hospital. AB - Despite available guidelines on indications for fresh-frozen plasma (FFP) transfusion, inappropriate use is increasing worldwide. We evaluated FFP administration to patients admitted to the Steve Biko Academic Hospital over 4 months, including indications for use and completeness of requisition forms. Transfusions were considered inappropriate for 39.5% of units administered. Of request forms submitted, only 22% had sufficient information for the blood transfusion services of the indication for transfusion. Transfusion with FFP is a medical intervention that carries risks and should be undertaken with care. Although this study was conducted in one centre, it is evident that clinicians' lack of knowledge of the indications for administration of FFP is widespread. Intervention is necessary to improve patient outcomes and reduce expenditure. PMID- 22668909 TI - Helicobacter pylori eradication: A randomised comparative trial of 7-day versus 14-day triple therapy. AB - Background. Helicobacter pylori is associated with several upper gastrointestinal conditions including chronic gastritis, peptic ulcer disease, and gastric malignancy. Proton pump inhibitor-based triple therapies are considered the standard regimens for H. pylori eradication, but the optimal duration of therapy is controversial. To prevent infection and complications, local studies should be undertaken to evaluate H. pylori eradication rates in a country. Objectives. We compared 7-day and 14-day regimens to determine the optimum duration of triple therapy for H. pylori eradication. Methods. We undertook a prospective randomised comparative trial of 7-day and 14-day triple therapy regimen for H. pylori eradication at the Aga Khan University Hospital, Nairobi; 120 patients with dyspepsia and H. pylori infection were randomised to receive esomeprazole, amoxicillin and clarithromycin for either 7 days (EAC 7) or 14 days (EAC 14). Compliance and side-effects were assessed 2 weeks after the start of therapy and H. pylori eradication was assessed by stool antigen tests 4 weeks after treatment. Results. Both the intention-to-treat (ITT; N=120) and per protocol (PP; N=97) analyses showed no significant differences between the eradication rates of EAC 7 (ITT 76.7%; PP 92%) and EAC 14 (ITT 73.3%; PP 93.6%) (ITT p=0.67; PP p=0.76). Poor compliance was reported in one patient in the EAC 14 group. The incidence of adverse events was comparable in the two groups. Conclusion. One week and 2-week triple treatments for H. pylori eradication are similar in terms of efficacy, safety and patient compliance. PMID- 22668910 TI - Suicidal ideation and attempt among South African medical students. AB - International data reveal that medical students are at higher risk of attempting suicide than the general population. We aimed to determine the prevalence of suicidal ideation and attempt among South African medical students from three universities and identify key predisposing risk factors. Data were collected via a questionnaire to medical students on demographics, mental health history, depressive symptoms, suicidal ideation and attempt. A total of 874 medical students from three universities were enrolled. We found a high prevalence of suicidal ideation (32.3%) and suicidal attempt (6.9%), which is three times higher than the general age-appropriate South African population. Simple screening questionnaires can identify such students, enabling universities to provide targeted and improved support for at-risk students. PMID- 22668911 TI - A randomised controlled trial on suture materials for skin closure at caesarean section: Do wound infection rates differ? AB - Objective.The aim of this study was to determine wound complication rates following the use of suture materials and staples for skin closure at caesarean section (CS). STUDY DESIGN: A randomised, controlled, prospective study was undertaken. Results. A total of 1 100 women was assigned randomly into 3 groups: polyglycolic acid (PGA) suture group (N=361), skin staple (SS) group (N=373) and nylon suture group (N=366). The overall wound infection rate was 7%. There was no difference in respect of number of patients, age, parity and gestation between the study groups. Those who had nylon sutures as opposed to PGA sutures were 9.5 times more likely to experience wound infection (p=0.055). Women who had SS were at 6.93 times higher risk of wound infection than those who had PGA sutures (p=0.014). Other factors influencing wound infection rates included: rupture of membranes >12 hours were 13.7 times (95% confidence interval (CI) 3.9 - 47.9, p<0.0001) more likely to have wound infection than those with rupture of membranes <12 hours. For every 1-minute increase of surgery duration, the risk of infection increased 1.094 times (95% CI 1.046 - 1.145; p<0.0001). HIV-infected women were 53.4% less likely to develop wound infection than their uninfected counterparts (odds ratio 0.466, 95% CI 0.238 - 0.913; p=0.026). As the time period of observation increased from baseline to day 3 and from day 3 to day 10, wound infection risk increased by 35 times (95% CI 8.155 - 150.868; p<0.001). Conclusion.The use of SS for CS wound closure is associated with a significantly greater risk of wound infections. SS for wound closure at CS is not recommended for use in South African district hospitals. PMID- 22668912 TI - CPD Questionnaire. PMID- 22668913 TI - UCT@100.great! PMID- 22668914 TI - 100 years of UCT's Faculty of Health Sciences. PMID- 22668915 TI - Contributions of the University of Cape Town to medical science in the first 100 years: personal reflections. AB - The contributions of the University of Cape Town's Health Sciences Faculty to medical science through research over the past 100 years are reviewed. The application of contemporary techniques to common medical problems in the developing world had important implications globally. The faculty can be proud of its achievements in many areas important to the health of people in South Africa, Africa and beyond. PMID- 22668916 TI - UCT's Medical Faculty and Groote Schuur Hospital. AB - A relationship has existed between the University of Cape Town's Medical Faculty (MF) and Groote Schuur Hospital (GSH) since the MF was established in 1912. However, this was not formalised until the first Joint Staff Agreement was signed in 1951. This close and rewarding association achieved outstanding results and produced significant benefits for both institutions over many years, despite intermittent problems and disputes. More recently, difficulties have been experienced, but it is hoped that these will be overcome. PMID- 22668917 TI - The place and the person: named buildings, rooms and places on the campus of the Faculty of Health Sciences, University of Cape Town. AB - The University of Cape Town Faculty of Health Sciences, in its hundredth year, carries a strong current of its development in the inscriptions on its pediments, doorways and notice boards. These names describe the Faculty in each of its stages of evolution, and evoke a rich history. The named look down from their portraits with pride at the passing students, the staff, and the flourishing Faculty. PMID- 22668918 TI - The Students' Health and Welfare Centres Organisation (SHAWCO) of the University of Cape Town: a review of the past 69 years. AB - The Students' Health and Welfare Centres Organisation (SHAWCO) is a student-run non-profit community development organisation based at the University of Cape Town (UCT). In 2012, SHAWCO celebrates its 69th anniversary, making it the oldest active student-run free clinic in South Africa. Over the past 7 decades, SHAWCO has become an integral part of the UCT Faculty of Health Sciences. This article reviews its history, current activities, and plans for the future. PMID- 22668919 TI - Health activism in Cape Town: a case study of the Health Workers Society. AB - The Health Workers Society (HWS), founded in 1980, was one of several progressive health organisations that fought for a democratic health system in South Africa. We document the sociopolitical context within which it operated and some of its achievements. HWS, many of whose members were staff and students of the University of Cape Town (UCT), provided a forum for debate on health-related issues, politics and society, and worked closely with other organisations to oppose the apartheid state's health policies and practices. They assisted with the formation of the first dedicated trade union for all healthcare workers and were one of the first to pioneer the primary healthcare approach in an informal settlement in Cape Town. PMID- 22668920 TI - From medical manners to moral reasoning: an historical overview of bioethics in the University of Cape Town's Faculty of Health Sciences. AB - The history of bioethics in the Faculty of Health Sciences of the University of Cape Town (UCT) follows a similar pattern to elsewhere. At first, bioethics received little formal attention, but there has been a flowering of interest over the last few decades. There has also been a shift from a professionally insular view of bioethics to one informed by non-medical disciplines. While this pattern is to be found in many parts of the world, there are some distinctive, but not unique, features of bioethics at South Africa's oldest medical school. PMID- 22668921 TI - Our surgical heritage: the role of the Department of Paediatric Surgery in the development of paediatric surgery in Cape Town, in Africa, and around the world. AB - The Department of Paediatric Surgery at the University of Cape Town has made a remarkable contribution to the academic body of knowledge of Paediatric Surgery both in South Africa and around the world. It has played a key role in the development of the specialty in South Africa and through the South African diaspora has trained many paediatric surgeons who have made their mark internationally. More recently it has become a major focus of teaching and training for African paediatric surgeons. This article traces this legacy through its origins in the early 1920s to its current prominent position in the world paediatric surgical community. PMID- 22668922 TI - The state and future of research at the University of Cape Town's Faculty of Health Sciences. AB - The nature of research has continued to change considerably over the last century. Our Faculty's challenge has been to keep abreast of those changes to remain at the cutting edge, while contributing meaningfully to the scientific literature which informs clinical and public health practice in South Africa and beyond. The Faculty must possess an agreed-on research strategy that is dynamic and responsive. Over the years our Faculty has 'grown' such a strategy document. This article, summarising its main thrusts, is offered because we feel that while it applies specifically to UCT, the issues raised surely apply to all similar faculties in our country and on the continent, to varying degrees. PMID- 22668923 TI - Anaesthesia - what has the University of Cape Town contributed? AB - From humble beginnings, the University of Cape Town's Department of Anaesthesia has played a major role in the development of anaesthesia as a speciality, in South Africa and internationally. We highlight these contributions in clinical service, teaching and research, with particular emphasis on the department's leading role in the evolution of anaesthetic safety in adults and children: from the development of the treatment of malignant hyperthermia, to unique studies in mortality associated with anaesthesia, and modern contributions to improved drug safety. Innovations in anaesthetic techniques have contributed to significant surgical developments, including the first heart transplant. Furthermore, our research has contributed to major advances in obstetric and endocrine anaesthesia, and training in the department is recognised as being among the best in the world. PMID- 22668924 TI - The gynaecological subspecialties: advances in women's health. AB - Under Professor Dennis Davey's leadership, the Department of Obstetrics and Gynaecology recognised the need for subspecialist expertise and training. Thus, the gynaecological subspecialties were developed, the first of which was gynaecological oncology. We review the research, and subsequent clinical application, which has evolved from the subspecialist units. PMID- 22668926 TI - From the pursuit of excellence to the quest for significance: promotion of a Childsafe South Africa. AB - Trauma represents a major burden of disease in South Africa. Children are disproportionately affected by trauma; rightly, childhood trauma can be referred to as 'the neglected childhood killer disease'. Unlike the field of infectious diseases, where vaccinations and prevention are the norm, paediatric trauma is usually ignored and prevention strategies are scarce. In this article, we review paediatric trauma and its effect on our society in light of the development of more effective child safety promotion strategies. PMID- 22668925 TI - Fifty years of porphyria at the University of Cape Town. AB - The porphyrias are a group of disorders resulting from defective haem biosynthesis. One form, variegate porphyria, is common in South Africa as a result of a founder effect. Over the past 50 years, the University of Cape Town Faculty of Health Sciences has built and maintained an international reputation for excellence in the field of porphyria. The porphyria group is respected for its research and for its accumulated experience in the management of these disorders. Equally important has been the comprehensive and holistic care offered to patients with porphyria, and to their families. PMID- 22668927 TI - UCT taught me how to challenge beliefs. AB - The world's first successful human heart transplantation on 2 December 1967 inspired me to study medicine at the University of Cape Town Faculty of Health Sciences. There I learned 5 key elements for a successful career in either medicine or science or both - perfectionism, passion, compassion, the dispassionate investigation of all the available evidence, and the need to challenge established beliefs for which the scientific evidence appears imperfect. Challenging such beliefs enabled us to prove that hyponatraemic encephalopathy was caused by persistent and heroic over-drinking during prolonged exercise, usually lasting more than 4 hours, and was unrelated to salt losses in sweat and urine; to understand that the brain not the muscles must regulate the exercise performance, and thus develop the Central Governor Model of Exercise; and to reconsider the dietary causes of the obesity and diabetic epidemic. PMID- 22668928 TI - A rural perspective: four stories. AB - These brief reflections from 4 University of Cape Town (UCT) medical graduates who chose to make their careers in rural practice are written in narrative style to try to capture something of the lived experience of working in rural areas. Although still the career choice of a minority of UCT graduates, those who have chosen to practise in rural areas have found a solid base of competence and confidence in their clinical skills, that has enabled them to tackle challenges in areas beyond anything that they or their teachers might have anticipated. PMID- 22668929 TI - The UCT Surgical Society - a society on the cutting edge. AB - The University of Cape Town Surgical Society is a student-run society established in 2006 and is affiliated with the Department of Surgery. The aims of the society are to supplement undergraduate training, to promote medical and surgical research, and to motivate students to pursue a career in surgery. Regular monthly lectures and surgical skills courses are offered, as well as weekly anatomy workshops. A recently launched Shadow Programme enables students to interact with practising surgeons in theatre, thereby gaining insight into the advantages and challenges involved in a future career in surgery. PMID- 22668930 TI - SATVI - after 10 years closing in on a new and better vaccine to prevent tuberculosis. AB - The vision of the South African Tuberculosis Vaccine Initiative (SATVI) (www.satvi.uct.ac.za) is 'A World Without TB' and our mission is 'Innovative and high-quality TB vaccine research in Africa, to impact the global epidemic'. Over the last 10 years, our focus has been twofold: first, clinical trials of BCG and of new candidate vaccines, and second, complementary research that addresses critical questions in TB vaccine development. SATVI is now widely regarded as the leading TB vaccine clinical research site in the world. PMID- 22668931 TI - From comprehensive medicine to public health at the University of Cape Town: a 40 year journey. AB - We explore the history of the School of Public Health at the University of Cape Town and its relationship to changes in the understanding of the role of public health both nationally and internationally. We draw from primary and secondary sources to trace the emergence, growth and development of the School, and to situate these processes within the socio-political, clinical and public health contexts in South Africa and internationally. PMID- 22668932 TI - UCT's contribution to medical genetics in Africa - from the past into the future. AB - The Division of Human Genetics (DHG), Faculty of Health Sciences, University of Cape Town (UCT) - established in 1972 - recently celebrated its 40th anniversary. We review its history, current status and future objectives. Dr Stuart Saunders, former Professor of Medicine and Vice-Chancellor of UCT, played a pivotal role in initiating the DHG. Dr Peter Beighton served as Professor of Human Genetics from 1972 to 1999. In this period, the initial focus was on medical genetics and the development of cytogenetic, biochemical and molecular laboratories, with the help of Prof Jacquie Greenberg. Fourteen clinical and scientific DHG members obtained doctorates; of these, 8 achieved full professorial status. Current Head of the Department, Prof Raj Ramesar, succeeded to the Chair in 1999. Expansion of the molecular laboratories followed. The DHG now has comprehensive programmes for postgraduate scientific training, research and service. Publications during the lifetime of the DHG include more than 540 articles in peer-reviewed medical, genetic and scientific journals, 20 books and contributions to over 40 chapters/editorials in scientific and medical genetic books. PMID- 22668933 TI - No health without mental health: establishing psychiatry as a major discipline in an African Faculty of Health Sciences. AB - Psychiatry has not always been a major clinical discipline in medical schools. Although the Faculty of Health Sciences of the University of Cape Town (UCT) celebrates its Centenary in 2012, a closely aligned major psychiatric hospital is older than the Medical School, while the Department of Psychiatry is only 50 years old. These differing dates reflect the history of and challenge for psychiatry; mental disorders contribute a major portion of the burden of disease, while appropriate recognition and resourcing of services and training has been delayed. There are ongoing challenges in aligning the visions of an old state-run system that focused on those with severe psychotic illness, a newer governmental vision of the importance of treating mental disorders in the community, the realities of current under-resourcing, and the international aspiration that psychiatry is one of the clinical neurosciences. Nevertheless, considerable strides have been made towards moving psychiatry from the periphery of society and medicine to a central discipline within the Faculty of Health Sciences at UCT. PMID- 22668934 TI - South African HIV-1 vaccine candidates - the journey from the bench to clinical trials. AB - Around 2.5 million people become infected with human immunodeficiency virus (HIV) each year. This extraordinary toll in human life and public health worldwide will only be reversed with effective prevention. Vaccination is regarded as the most effective way to prevent infectious disease. However, there are many challenges to overcome before a successful prophylactic HIV vaccine will be available. We are participating in a global effort to develop and test candidate HIV vaccines. Two candidate prophylactic HIV vaccines that were designed and developed at the University of Cape Town (UCT) entered phase 1 clinical trials in the USA and South Africa in 2009, after a 9-year development period. In addition to the vaccines in clinical trial, there is a pipeline of candidate HIV-1 subtype C vaccines including virus-like particles, novel DNA vaccines, capripoxvirus and Bacillus Calmette-Guerin (BCG)-vectored vaccines. This article describes the history of HIV vaccine research at UCT, and the partnerships that made the project possible. PMID- 22668935 TI - Biomedical engineering at UCT - challenges and opportunities. AB - The biomedical engineering programme at the University of Cape Town has the potential to address some of South Africa's unique public health challenges and to contribute to growth of the local medical device industry, directly and indirectly, through research activities and postgraduate education. Full realisation of this potential requires engagement with the clinical practice environment and with industry. PMID- 22668936 TI - Approaches to target identification and validation for tuberculosis drug discovery: a UCT perspective. AB - Tuberculosis (TB) disproportionately affects a few high-burden countries including South Africa. In these regions, basic TB research is rare, endemic countries being valued primarily as sites for drug trials and clinical studies. Our basic mycobacterial research focuses on current approaches to drug target identification and validation within the context of international trends in TB drug discovery. Increased funding for TB drug development globally prompted a significant shift in the composition of drug discovery consortia, with academic laboratories assuming a major role in collaboration with industrial partners. This hybrid model holds promise for the expansion of local programmes, especially where actively supported by government. However, the application of industry standard business practices to research projects involving biology and chemistry expertise demands a greater appreciation of the differences between a chemically, versus biologically, validated drug target, and of the factors informing these differences. PMID- 22668937 TI - Shedding the load of hypertension: the proteolytic processing of angiotensin converting enzyme. AB - A number of membrane proteins are enzymatically cleaved or 'shed' from the cell surface, resulting in the modulation of biological events and opening novel pharmaceutical approaches to diverse diseases by targeting shedding. Our focus has been on understanding the shedding of angiotensin-converting enzyme (ACE), an enzyme that plays a pivotal role in blood pressure regulation. The identification of novel hereditary ACE mutations that result in increased ACE shedding has advanced our understanding of the role of ACE shedding in health and disease. Extensive biochemical and molecular analysis has helped to elucidate the mechanism of ACE shedding. These findings point to the potential therapeutic role of targeting shedding in regulating tissue ACE levels in cardiovascular disease. PMID- 22668938 TI - Haematological complications of HIV infection. AB - South Africa is in the midst of the world's largest human immune deficiency virus (HIV) epidemic with an estimated 5.6 million people infected. Haematological manifestations of HIV are common and diverse, occurring at all stages of infection. Haematological emergencies occurring in this setting include the high grade lymphomas, particularly Burkitt lymphoma, and thrombotic thrombocytopenic purpura (TTP). Immune thrombocytopenic purpura (ITP), opportunistic infections and drug side-effects are also frequent causes of cytopenias. A bone marrow biopsy has a high diagnostic utility in HIV patients presenting with unexplained cytopenias and/or fevers. It is not widely realised that HIV is also a prothrombotic state with an increased incidence of thromboembolic disease. Highly active antiretroviral therapy (HAART) is now widely available in South Africa and is a crucial adjunct to therapy of haematological complications. Medical professionals across all disciplines need to be alert to the haematological complications of HIV infection. PMID- 22668939 TI - Masithethe: speech and language development and difficulties in isiXhosa. AB - IsiXhosa is the second most spoken language in South Africa and one of its official languages. Spoken mainly in the Eastern and Western Cape regions it is fitting that much of the research focusing on children's isiXhosa speech and language acquisition has been carried out at the University of Cape Town (UCT). We describe what is known about children's acquisition of isiXhosa, and highlight studies which inform our knowledge of the typical development of the language in relation to the acquisition of consonants including clicks and the isiXhosa noun class system. Little is known about the specific nature of speech and language difficulties in isiXhosa, and the development of isiXhosa resources for speech and language assessment and therapy is in its infancy. Suggestions are made for advancing knowledge and practice which is needed to provide a relevant and quality service to isiXhosa speakers. PMID- 22668940 TI - Herpetic ulcer of the eyelids in an immunocompromised patient. AB - A 24-year-old black female (HIV-positive) was referred to our clinic with a 4 week history of an ulcerative lesion of the right upper and lower eyelids. She was on treatment for pulmonary tuberculosis and had been admitted to a secondary level hospital. She had no other ocular symptoms or signs. A tissue biopsy of the lesion revealed multinucleate squamous cells with ground glass viral nuclear inclusion bodies, indicative of herpes simplex virus (HSV) infection. The ulcer healed with oral and topical acyclovir therapy, confirming a herpetic origin. There is only one other reported case of this type of ulcerative eyelid lesion caused by HSV; the patient in this case was also immunocompromised. PMID- 22668941 TI - The complexity of HIV vasculopathy. AB - We present a case and discuss stroke related to human immunodeficiency virus (HIV) infection and the difficulties of reaching a firm diagnosis of the cause of the aneurysmal vasculopathy. In the absence of a clear aetiology we suggest looking for varicella zoster virus (VZV) replication in the cerebrospinal fluid (CSF) by polymerase chain reaction (PCR) and treating with intravenous acyclovir, aiming for HIV control with appropriate antiretroviral therapy and providing suitable antiplatelet agents. If there is a high index of suspicion of VZV, therapy with acyclovir may be prudent even if the CSF PCR is negative (as may occur after the first 2 weeks of reactivation of infection). Determination of a VZV plasma:CSF IgG ratio is not readily available and would only provide surrogate support for a previous VZV infection in the central nervous system compartment. PMID- 22668942 TI - Health Sciences undergraduate education at UCT: a story of transformation. AB - Undergraduate education and training in the Faculty of Health Sciences at the University of Cape Town has become socially responsive. A story of transformation that is consonant with wider societal developments since the 1994 democratic elections, outlining the changes in undergraduate curricula across the faculty, is presented. PMID- 22668943 TI - Polyglutamine disease: from pathogenesis to therapy. AB - Polyglutamine diseases are inherited neurodegenerative conditions arising from expanded trinucleotide CAG repeats in the disease-causing gene, which are translated into polyglutamine tracts in the resultant protein. Although these diseases share a common type of mutation, emerging evidence suggests that pathogenesis is complex, involving disruption of key cellular pathways, and varying with the disease context. An understanding of polyglutamine disease mechanisms is critical for development of novel therapeutics. Here we summarise theories of molecular pathogenesis, and examine ways in which this knowledge is being harnessed for therapy, with reference to work under way at the University of Cape Town. Despite a plethora of preclinical data, clinical trials of therapies for polyglutamine diseases have had only limited success. However, recently initiated trials, including those using gene silencing approaches, should provide valuable insights into the safety and efficacy of therapies directly targeting polyglutamine pathogenesis. This is particularly relevant in the South African context, where the frequencies of two polyglutamine diseases, spinocerebellar ataxia types 1 and 7, are among the highest globally. PMID- 22668944 TI - Improving poisoning diagnosis and surveillance of street pesticides. AB - An effective surveillance system is required to reduce pesticide exposures and poisonings, especially from street pesticides (illegal, unlabelled, and decanted agricultural pesticides used predominately for urban household purposes). Poisoning from any pesticide class, not only organophosphates, constitutes a medically notifiable condition in South Africa. Current practice, however, is to report only organophosphate cases, resulting in severe under-reporting. The lack of data concerning the link between poisonings and street pesticides has led to the mistaken assumption that urban populations are not at risk from significant pesticide exposures and poisonings. Without accurate statistics, healthcare professionals and policy makers are unaware of the contribution of street pesticide poisonings to the overall health burden. Accurate diagnosis is a prerequisite for notification and subsequent surveillance. An algorithm has been developed to enable healthcare professionals to improve the diagnosis and notification of pesticide poisonings. PMID- 22668945 TI - What healthcare financing changes are needed to reach universal coverage in South Africa? AB - The national health insurance proposed for South Africa aims to achieve a universal health system. The best way to identify the financing mechanism that is best suited to achieving this goal is to consider international evidence on funding in universal health systems. The evidence from Organisation for Economic Cooperation and Development countries and a number of middle-income countries that have achieved universal coverage clearly indicates that mandatory pre payment financing mechanisms (i.e. general tax funding, in some cases supplemented by mandatory health insurance) must dominate, with a clearly specified, complementary role for voluntary or private health insurance. PMID- 22668946 TI - Cardioprotection from metabolism to molecules to certainties. AB - Starting millions of years ago, the heart developed metabolic and molecular cardioprotective paths. The concept of metabolic protection includes the recent successful early provision of glucose-insulin-potassium (GIK) to patients with acute coronary syndromes in the ambulance to inhibit high harmful free-fatty acid levels. Molecular cardioprotective pathways also developed in primeval times. The 2 major paths are the RISK (Reperfusion Injury Salvage Kinases) path and the SAFE (Survival Activating Factor Enhancement) path, on which our group in Cape Town has focused. These paths help to lessen ischaemic-perfusion damage, and may, hypothetically, also be activated by intense exercise. PMID- 22668947 TI - Inflammatory pathways in cervical cancer - the UCT contribution. AB - Cervical cancer is the leading gynaecological malignancy in Southern Africa. The main causal factor for development of the disease is infection of the cervix with human papillomavirus. It is a multi-step disease with several contributing co factors including multiple sexual partners, a compromised immune system and cervical inflammation caused by infections with Chlamydia trachomatis or Neisseria gonorrhoeae. Inflammation involves extensive tissue remodelling events which are orchestrated by complex networks of cytokines, chemokines and bio active lipids working across multiple cellular compartments to maintain tissue homeostasis. Many pathological disorders or diseases, including cervical cancer, are characterised by the exacerbated activation and maintenance of inflammatory pathways. In this review we highlight our findings pertaining to activation of inflammatory pathways in cervical cancers, addressing their potential role in pathological changes of the cervix and the significance of these findings for intervention strategies. PMID- 22668948 TI - Renal transplantation between HIV-positive donors and recipients justified. AB - HIV infection was previously an absolute contraindication to renal transplantation. However, with the advent of highly active antiretroviral therapy (HAART), renal transplantation using HIV-negative donor kidneys has successfully been employed for HIV-infected patients with end-stage renal failure. In resource limited countries, places on dialysis programmes are severely restricted; HIV infected patients, like many others with co-morbidity, are often denied treatment. Kidneys (and other organs) from HIV-infected deceased donors are discarded. The transplantation of HIV-positive donor kidneys to HIV-infected recipients is now a viable alternative to chronic dialysis or transplantation of HIV-negative donor kidneys. This significantly increases the pool of donor kidneys to the advantage of HIV-positive and -negative patients. Arguments are presented that led to our initiation of renal transplantation from HIV-positive deceased donors to HIV-positive recipients at Groote Schuur Hospital, Cape Town. PMID- 22668949 TI - The prevalence and burden of pain and other symptoms among South Africans attending highly active antiretroviral therapy (HAART) clinics. AB - BACKGROUND: Since the advent of antiretrovirals, HIV disease has largely come to be considered a chronic disease for those able to access treatment. As such, the concept of 'living well' with HIV is important. Increasing evidence suggests a high symptom burden in HIV that persists in the presence of treatment. OBJECTIVES: Our study aimed to measure the prevalence and burden of pain and other physical and psychological symptoms among South African HIV-positive patients attending highly active antiretroviral therapy (HAART) clinics. METHODS: The study design was a cross-sectional survey. Simple random sampling was used to recruit 385 adult participants. RESULTS: The sample had a median age of 40 years (Q1 - Q3=33 - 46) and 98.4% were on HAART. The mean latest CD4 count for the participants was 355.06+/-219/mm3. The mean number of symptoms of the 32 symptoms on the MSAS-SF experienced by participants was 10.24+/-5.71 (range 1 - 28). All 4 psychological symptoms were in the top 10 most prevalent symptoms, with feeling sad being the most prevalent symptom overall. CONCLUSIONS: The high prevalence of symptoms and the high symptom burden experienced by the participants in this survey suggest inadequate symptom control and highlight the palliative care needs of an ambulant patient population already on HAART. Extension of life without reasonable efforts to also address the patient's quality of life is not ethically justifiable. In addition, more research appears to be required to answer whether these findings are associated with sub-optimal HAART adherence. PMID- 22668950 TI - Remote sensing of HIV care programmes using centrally collected laboratory results: can we monitor ART programme effectiveness? AB - AIMS: We describe a monitoring system at population level of patients on antiretroviral therapy (ART) using centrally collected laboratory data. We demonstrate an analogous process of remote sensing using a large set of laboratory results and illustrate the tremendous density of information stored. We moved from an individual to a community view of ART rollout, similar to remote sensing used in the earth and biological sciences when the spatial scale of the investigation is too large to be performed at ground level. METHODS: This was a retrospective cohort study of patients from January 2004 to June 2011. A total of 188 759 individual laboratory results representing 26 445 patients were analysed for average CD4 and viral load by year. RESULTS: The data showed an increasing state of health of the population and allowed for hypothesis generation when the trends did not follow expected paths. CONCLUSION: In this analysis we moved away from individual-centred data to population-level data in order to assess ART programme performance. Routine patient-monitoring data had great utility in assessment of population health. These methods are useful in monitoring and evaluation and effectiveness studies as they are easy to collect, reliable (not requiring much human matching or interventions) and scalable from a single clinic to an entire population. The larger the sample size, the more reliable the results, as confounders (such as incorrectly identified transfers out, lost-to follow-up patients and transfers in) would be removed. PMID- 22668951 TI - Burden of antituberculosis and antiretroviral drug-induced liver injury at a secondary hospital in South Africa. AB - BACKGROUND: G F Jooste Hospital (GFJH) is a secondary-level referral hospital in a high HIV and tuberculosis (TB) co-infection setting. AIMS: To assess the proportion of significant drug-induced liver injury (DILI) due to tuberculosis treatment (TBT) and/or antiretroviral therapy (ART) among patients presenting with liver dysfunction at GFJH and to describe management and outcomes. METHODS: A retrospective observational study was performed of all cases referred to GFJH with significant liver dysfunction from 1 January to 30 June 2009. Significant liver dysfunction was defined by alanine transaminase (ALT)>=200 U/l or total bilirubin (TBR)>=44 umol/l. TBT- or ART-associated DILI was defined as significant liver dysfunction attributed to TBT and/or ART and which resulted in the halting of treatment or the adjustment thereof. Outcome measures included case numbers, descriptive data, and in-hospital and 3-month mortality. RESULTS: A total of 318/354 cases of significant liver dysfunction were reviewed: 71 were classified as TBT- or ART-associated DILI, while liver dysfunction was attributed to other causes in the remainder. In-hospital and 3-month mortality of TBT- or ART-associated DILI patients was 27% (n=19) and 35% (n=25), respectively. The majority of deaths were related to sepsis or sepsis complicating liver dysfunction. Twenty-three patients (32%) were lost to follow-up; 23 (32%) were alive and in outpatient care 3 months after presentation. CONCLUSIONS: TBT- or ART-associated DILI is a common reason for presentation at a referral hospital in South Africa. In-hospital and 3-month mortality are high. Prospective studies are needed to define optimal management. PMID- 22668952 TI - Immunological characterisation of an unmasking TB-IRIS case. AB - BACKGROUND: Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an early complication of combination antiretroviral therapy (cART). Two forms are recognised: (i) paradoxical - recurrent or new TB symptoms develop after cART initiation in patients receiving TB treatment prior to cART; and (ii) unmasking TB-IRIS - active TB presents within 3 months of cART in patients not receiving TB treatment at cART initiation. The latter has heightened clinical manifestations and a marked inflammatory presentation. AIM: To gain insight into the immune pathogenesis of a case of unmasking TB-IRIS. METHODS: The patient was recruited when starting cART and followed up at 4, 12 and 24 weeks of treatment. Peripheral blood mononuclear cells were used for flow cytometry. RESULTS: Immunological analysis indicated increased CD4+ T-cell proportions from 1.1% at baseline to 14% at 24 weeks (the CD4 count increased from 4 cells/ul at baseline to 41 cells/ul at 24 weeks). HIV viral load fell from 460 774 to 1 405 copies/ml during the same period. The proportion of TB antigen (PPD)-specific CD4+IFN gamma+ cells increased from 0.4% at baseline and 4 weeks (IRIS onset) to 7.8% at 12 weeks (after resolution of the IRIS episode); this fell to 0.7% at 24 weeks. The surface phenotype of CD4+IFN-gamma+ cells during the episode was CD45RO+, CD45RA-, CCR7-, CD62L-, CCR5+/- and CD69-. We found a distorted balance between central memory and effector memory T-cells at cART commencement that might have predisposed the patient to unmasking TB-IRIS. We showed that this might have reflected compromised thymic output. Discussion. While it has been suggested that tuberculin-specific Th1-responses induce TB-IRIS in HIV co-infected patients, our data in this case indicated that these cells were expanded only after IRIS onset and were therefore not inducing TB-IRIS. CONCLUSION: We describe, in hitherto unpublished detail, the immunological characterisation of an unmasking TB-IRIS case; we show that thymic output may be compromised at IRIS onset. PMID- 22668953 TI - Advances in childhood tuberculosis - contributions from the University of Cape Town. AB - Childhood tuberculosis (TB) is common in high TB burden countries, contributing a substantial proportion to the TB caseload. The HIV epidemic has had a large impact on the incidence, diagnosis and management of childhood TB. AIM: To review the contributions from researchers at the University of Cape Town to the field of childhood TB over the past decades. METHODS: Review of published literature on studies of childhood TB done by investigators from the University of Cape Town. RESULTS: Important advances have been made, especially in the areas of epidemiology, diagnosis and prevention of childhood TB. Epidemiological research has led to improved understanding of the large burden of childhood TB in Cape Town. Advances in diagnosis include use of improved specimens, particularly induced sputum and better diagnostic tests. The efficacy of GeneXpert, a rapid polymerase chain reaction (PCR)-based diagnostic test, on induced sputum specimens, has potential to enable a confirmed diagnosis in children of all ages at a range of healthcare facilities, and represents an important advance in management of children presenting with suspected TB. Advances in prevention include the establishment of a vaccine study site and several studies on immunisation, and on the use of primary isoniazid prophylaxis as an effective preventive strategy in symptomatic HIV-infected children. CONCLUSION: Research in childhood TB has led to important advances in diagnosis and management, enabling better care for HIV-infected and uninfected children. PMID- 22668954 TI - The effect of physiological concentrations of bile acids on in vitro growth of Mycobacterium tuberculosis. AB - BACKGROUND: Intestinal tuberculosis occurs mainly in the terminal ileum and caecum, where the concentration of bile acids is lowest, and rarely in the upper digestive tract. OBJECTIVES: We examined the effect of physiological concentrations of bile acids on the in vitro growth of Mycobacterium tuberculosis (MTB). METHODS: The 4 major bile acids, lithocolic acid, cholic acid, deoxycholic acid and chenodeoxycholic acid, were added to individual Lowenstein-Jensen (LJ) culture media at physiological concentrations. A combined LJ medium was also prepared using all 4 bile acids. These were double-diluted 4 times by the addition of LJ media. Each culture medium was inoculated with the H37Rv strain of MTB and incubated at 37 degrees C for 8 weeks. MTB growth was measured at 2 and 8 weeks in a semiquantitative fashion using cut-offs of >5, >10, >20, >100 colony forming units. RESULTS: All lithocolic acid cultures showed uninhibited TB growth at 2 and 8 weeks. Chenodeoxycholic acid, deoxycholic acid and cholic acid alone, and in combination, showed concentration-dependent inhibition of MTB growth at 2 and 8 weeks. Four cultures were lost to contamination. CONCLUSIONS: Certain bile acids alone and in combination, at physiological concentrations, inhibit the growth of MTB in vitro. This might explain why intestinal TB occurs in the ileocaecum in the majority of cases and why gallbladder TB is very rare. PMID- 22668955 TI - Complement component C5 and C6 mutation screening indicated in meningococcal disease in South Africa. AB - BACKGROUND: Invasive meningococcal disease (MD), caused by Neisseria meningitidis infection, is endemic in South Africa, with a seasonal peak in winter and spring. There were 2 432 laboratory-confirmed cases between 2006 and 2010. Human deficiency of the fifth complement component (C5D) or complete absence of the sixth component (C6Q0) leads to increased risk of MD, which is often recurrent. All attacks are serious and can lead to death or severe long-term consequences. OBJECTIVE: To determine the frequency of specific disease-associated C5 and C6 gene mutations in patients presenting with MD in the Western Cape. RESULTS: In 109 patients with confirmed invasive MD investigated for local mutations known to cause C5D and C6Q0, 3 were C5D and 11 were C6Q0. In 46 black patients tested, 3 were C5D and 7 were C6Q0. In 63 coloured patients, none were C5D and 4 were C6Q0. All deficient patients were followed up and offered prophylaxis. CONCLUSION: C5D and C6Q0 are not rare genetic diseases in South Africa and affected patients are susceptible to repeated MD; 12.8% of MD patients tested were C5D or C6Q0. Blacks were at greatest risk with 21.7% being either C5D or C6Q0. We strongly recommend diagnostic testing for complement C5 and C6 deficiency in the routine work-up of all MD cases in South Africa. Prophylactic treatment should be started in susceptible individuals. PMID- 22668956 TI - The role of the infectious diseases unit at Groote Schuur Hospital in addressing South Africa's greatest burden of disease. AB - BACKGROUND: The greatest burden of disease in South Africa (SA) comes from infectious diseases (ID), with human immunodeficiency virus (HIV) and tuberculosis (TB) dominating the health landscape. However, other infections including community-acquired and imported infections and the rise in hospital acquired infections pose a considerable threat to public health. METHODS AND OBJECTIVES: We used a prospective cross-sectional study to examine the profile of patients referred to the Infectious Diseases Unit at Groote Schuur Hospital (GSH) between 2008 and 2011. RESULTS: A total of 2 142 patient consultations were performed, the majority at the request of secondary hospital level medical teams; 80% of patients were HIV-infected (with a median CD4 count of 128/mm3). Approximately half of antiretroviral-naive, HIV-infected patients started antiretroviral therapy in hospital. TB, predominantly extrapulmonary, was the most common diagnosis. Imported infections, notably severe falciparum malaria, accounted for a large number of the 81 different diagnoses in HIV-seronegative patients. Over half of all patients had co-morbidity complicating their clinical presentation. In-hospital mortality was 5.8%, with overwhelming sepsis the cause in 40% of deaths, largely due to hospital-acquired infection, particularly in the HIV-infected cohort. CONCLUSION: The overwhelming burden of ID in SA is revealed in this experience at GSH, a tertiary level referral hospital serving the Cape metropolitan area. The needs of the population warrant a reappraisal of human resource capacity and training in ID in SA. PMID- 22668957 TI - The characteristics of juvenile myasthenia gravis among South Africans. AB - OBJECTIVES: To report the characteristics of juvenile-onset (<20 years) myasthenia gravis (MG) in Africa. SUBJECTS AND METHODS: Six South African centres collected data which included acetylcholine receptor-antibody (AChR-ab) status, delay before diagnosis, MG Foundation of America grade at onset, maximum severity and severity at last visit, therapies, outcomes and complications. RESULTS: We report on 190 individuals with a 4-year median follow-up (interquartile range (IQR) 1 - 8). The median age at symptom onset was 7 years (IQR 4 - 14). Ocular MG (26%) occurred among younger children (mean 5.1 years), compared with those developing generalised MG (74%) (mean 10.2 years) (p=0.0004). Remissions were obtained in 45% of generalised and 50% of ocular MG patients, of whom the majority received immunosuppressive treatment, mainly prednisone. Children with post-pubertal onset had more severe MG, but deaths were infrequent. Thymectomies were performed in 43% of those with generalised MG who suffered greater maximum disease severity (p=0.002); there was a trend towards more remissions in the thymectomy group compared with the non-thymectomy group (p=0.057). There was no racial variation with respect to AChR-ab status, maximum severity, or use of immunosuppression. However, 23% of children of African genetic ancestry developed partial or complete ophthalmoplegia as a complication of generalised MG (p=0.002). CONCLUSION: Younger children developed ocular MG and older children generalised MG. Persistent ophthalmoplegia developing as a MG complication is not uncommon among juveniles of African genetic ancestry. A successful approach to the management of this complication that causes significant morbidity is, as yet, unclear. PMID- 22668958 TI - Phaco-emulsification versus manual small-incision cataract surgery in South Africa. AB - OBJECTIVES: To compare the results of phaco-emulsification cataract surgery and manual small-incision cataract surgery. METHODS: Consecutive patients aged >50 years undergoing surgery for age-related cataract were recruited into a randomised prospective clinical trial. Randomisation was done using opaque sequentially numbered envelopes opened by the surgeon immediately prior to surgery. The patients were seen after 1 day, 2 weeks, and 8 weeks. Outcome measures. The primary outcome measure was the uncorrected visual acuity at week 8. The secondary outcome measures were the uncorrected visual acuity on day 1, the best corrected visual acuity at week 8, the refraction at week 8, and the intra- and postoperative complications. RESULTS: One hundred patients were recruited into each arm of the study. There was no difference in the incidence of intra-ocular complications (p=0.19). There was no difference in the day 1 visual acuities (p=0.28). However, both the uncorrected and the corrected week 8 visual acuities were better in the eyes that had phaco-emulsification (p=0.02 and p=0.03), and there was less astigmatism (p=0.001) at week 8 in the eyes that had phaco-emulsification. CONCLUSIONS: While manual small-incision surgery has been recommended as an acceptable alternative to phaco-emulsification in middle- and low-income countries, we have found that the results of phaco-emulsification are better. Where appropriate, consideration should be given to encouraging a transition to phaco-emulsification in our Vision 2020 programmes in Africa. PMID- 22668959 TI - Early outcomes of thrombolysis for acute ischaemic stroke in a South African tertiary care centre. AB - BACKGROUND: Stroke is an important cause of death and disability in sub-Saharan Africa. Recombinant tissue plasminogen activator (tPA) thrombolysis is effective in treating acute ischaemic stroke, but may not be a viable option in developing countries. METHODS: We assessed the short-term outcomes and safety of tPA for the treatment of stroke at Groote Schuur Hospital from the year 2000. Patients with a clinical diagnosis of acute stroke with onset of stroke symptoms within 4.5 hours of receiving thrombolysis were included. Exclusion criteria were based on the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA trial protocol (upper age limit was 75 years). Primary outcomes were the proportion of patients achieving significant early neurological recovery defined as an improvement of 4 or more points on the National Institutes of Health stroke scale (NIHSS) score and functional independence defined as a modified Rankin score of 2 or less at discharge. The primary safety measures were the rates of symptomatic intracranial haemorrhage (SICH) and death. RESULTS: From January 2000 to February 2011 42 patients were thrombolysed, with a mean time to tPA infusion of 160 minutes (standard deviation (SD) 50; range 60 - 270). By discharge the median NIHSS score fell from 14 (interquartile range (IQR) 10.5 - 17) to 7.5 (IQR 1 - 15); 28 (66.7%) achieved significant neurological improvement, and 17 (40.5%) were functionally independent. Two patients (4.8%) suffered SICH and there were 3 (7.1%) deaths. CONCLUSION: Thrombolysis in routine clinical practice in a South African setting has similar safety and early efficacy outcomes to controlled trials and open-label studies in developing and developed countries. PMID- 22668960 TI - Functioning at 6 months post stroke following discharge from inpatient rehabilitation. AB - OBJECTIVES: To determine activity limitations, participation restrictions, health related quality of life and caregiver strain in community-dwelling stroke survivors discharged from an intensive inpatient rehabilitation programme at 6 months post stroke. METHODS: Fifty-one consecutive stroke patients admitted to a Western Cape rehabilitation centre were included. Community-dwelling participants (N=46) at 6 months post stroke were assessed using the Modified Rankin Scale (MRS), Barthel index (BI), Nottingham extended activities of daily living (NEADL) scale, Euroqol (EQ-5D) instrument and caregiver strain index (CSI). RESULTS: Most participants (73.9%) were independent in activities of daily living or had minimal disability (BI 75 - 100). However, according to the NEADL, many participants were not independent in housework (60.9%), food preparation (52.2%), shopping (80.4%) and public transport use (65.2%), implying the need for caregiver assistance. According to the MRS, 29% of participants were severely disabled, requiring caregiver assistance for basic needs, and 20% could not be left alone. Feelings of anxiety or depression were felt in 50% of participants and 59% reported pain or discomfort, according to the EQ-5D. High levels of caregiver strain were reported in 56% of caregivers (CSI). Follow-up after discharge was reported in few participants. CONCLUSIONS: Consideration should be given to support for stroke survivors and caregivers after discharge and whether targeted programmes can improve specific aspects of functioning, such as community mobility. PMID- 22668961 TI - Twelve-month outcomes of patients admitted to the acute general medical service at Groote Schuur Hospital. AB - OBJECTIVES: Hospitalisation for medical illness has ongoing impact on individuals, healthcare services and society beyond discharge. This study's objective was to determine the 12-month mortality and functional outcomes of patients admitted to the acute medical service at Groote Schuur Hospital (GSH). METHODS: Follow-up, using the hospital records system and provincial death registry, together with telephonic interviews or home visits, was attempted for 465 medical inpatients admitted to GSH between 14 September and 16 November 2009. Functional outcomes were assessed using the Katz activities of daily living (ADL) score and Barthel index (BI). Outcome measures. The major study outcomes included: 12-month mortality (overall and unexpected), changes in functional status and pre- and post-admission employment rates. RESULTS: Inpatient mortality was 11%. At 12-month follow-up, 35% (145/415) were deceased and 30% (125/415) could not be traced; 38% (55/145) of deaths were considered expected and unexpected mortality was associated with age >40 years (p=0.02) and an admission urea >7.0 mmol/l (p=0.004). Katz ADL deteriorated in 15% (21/143) of interviewed patients and was associated with age >50 years (p=0.005); 23% (33/143) had improved Katz ADL associated with admission human immunodeficiency virus (HIV) (p=0.01), tuberculosis (TB) infection (p=0.05) and sepsis (p=0.02). Employment rates declined from 41% (59/145) pre-admission to 18% (26/145) at 12 months (p<0.001), with little increase in the number of persons receiving disability grants. Twenty per cent (29/145) of patients required hospital readmission and this was associated with ADL functional decline (p=0.01). CONCLUSIONS: There was a very high overall mortality of 42% in patients admitted to the general medical wards. Significant employment decline and readmission rates highlight the additional economic and societal burdens of hospitalisation due to medical illness in the survivors. PMID- 22668962 TI - Outcome in decompensated alcoholic cirrhotic patients with acute variceal bleeding. AB - BACKGROUND: Variceal bleeding (VB) is the leading cause of death in cirrhotic patients with oesophageal varices. We evaluated the efficacy of emergency endoscopic intervention in controlling acute variceal bleeding and preventing rebleeding and death during the index hospital admission in a large cohort of consecutively treated alcoholic cirrhotic patients after a first variceal bleed. METHODS: From January 1984 to August 2011, 448 alcoholic cirrhotic patients (349 men, 99 women; median age 50 years) with VB underwent endoscopic treatments (556 emergency, 249 elective) during the index hospital admission. Endoscopic control of initial bleeding, variceal rebleeding and survival after the first hospital admission were recorded. RESULTS: Endoscopic intervention alone controlled VB in 394 patients (87.9%); 54 also required balloon tamponade. Within 24 hours 15 patients rebled; after 24 hours 61 (17%, n=76) rebled; and 93 (20.8%) died in hospital. No Child-Pugh (C-P) grade A patients died, while 16 grade B and 77 grade C patients died. Mortality increased exponentially as the C-P score increased, reaching 80% when the C-P score exceeded 13. CONCLUSION: Despite initial control of variceal haemorrhage, 1 in 6 patients (17%) rebled during the first hospital admission. Survival (79.2%) was influenced by the severity of liver failure, with most deaths occurring in C-P grade C patients. PMID- 22668963 TI - Treatment of carcinoma of the anal canal at Groote Schuur Hospital. AB - OBJECTIVES: Chemoradiation is the treatment of choice for squamous carcinoma of the anal canal, resulting in the same local control rates as surgery but with the advantage of organ function preservation. We aimed to review all cases of anal canal carcinoma treated at Groote Schuur Hospital between 2000 and 2004 and to assess treatement outcome. METHODS: The records for 31 patients presenting during this period were reviewed. Patient and tumour characteristics were recorded. Twenty-six patients were treated with chemoradiation. Local failure-free, colostomy-free and overall survival were calculated using the Kaplan-Meier method. RESULTS: Compared with the literature, the median patient age was younger and the stage was more advanced in this study. The complete response rate for all stages with chemoradiation was 80%. The local failure-free survival at 5 years was 60.7%. Colostomy-free and overall survival at 5 years were 59.2% and 65.6%, respectively. CONCLUSIONS: The patients presented with locally advanced disease. Chemoradiation is effective treatment for this group of patients and the majority avoid a permanent colostomy as they preserve anal sphincter function. PMID- 22668964 TI - Diagnosing breast cancer: an opportunity for innovative engineering. AB - BACKGROUND: In an ancient papyrus, dating back to 2500 BC, an Egyptian named Imhotep, thought to be the first physician and engineer in history, offers a glimpse into the earliest recorded case of breast cancer. Treatment has evolved over the years, from radical mastectomy to radiation by X-rays, and from adjuvant chemotherapy to hormonal therapy. A key challenge in fighting the 'war' on breast cancer is early diagnosis and here innovative engineers play a vital role. AIMS: While full-field digital mammography has emerged in the past decade, this technique suffers from relatively high dose levels and poor sensitivity when the breasts are dense. We aimed to develop a diagnostic imaging system that exposes the patient to lower ionising radiation and improves the sensitivity and specificity for women with dense breasts. RESULTS: Our PantoScanner platform has been designed to implement slot scanning digital X-rays, thereby lowering the dose and increasing signal-to-noise ratio, while also accommodating automated ultrasound and digital tomosynthesis. Early results based on mammographic phantoms are encouraging while the PantoScanner is undergoing clinical testing prior to commercial release. CONCLUSION: Since breast cancer kills 500 000 people globally every year, early diagnosis by breast screening could save the lives of many women. Our fervent hope is that the PantoScanner system will significantly contribute to this effort in South Africa and around the world. PMID- 22668965 TI - Lowering the alcohol content of red wine does not alter its cardioprotective properties. AB - BACKGROUND: Many epidemiological, clinical and laboratory studies suggest that chronic and moderate consumption of red wine benefits cardiovascular health, because of the alcoholic content or the polyphenols/flavonoids. AIMS: The antioxidant and cardioprotective properties of a French red wine (cabernet sauvignon, 12% alcohol by volume) were compared with those of the same wine subjected to reverse osmosis for partial removal of alcohol (6% alcohol by volume). METHODS: Antioxidant capacity was assessed in vitro using the oxygen radical absorbance capacity (ORAC) assay. To test the cardioprotective effect of 12% v. 6% wine, the drinking water of rats used for controls was supplemented with red wine (12% or 6%). After 10 days, hearts were isolated on a Langendorff system and subjected to 30 minutes of global ischaemia plus 30 minutes of reperfusion (I/R). RESULTS: No differences in antioxidant capacity were observed between wine of 12% and 6% alcohol content (n=8 per group). Control hearts subjected to I/R presented a rate pressure product (heart rate x left ventricular developed pressure, expressed as a percentage of baseline value) of 16+/-4% (mean+/-standard error). Pretreatment with wine 12% or 6% improved the rate pressure product to 40+/-6% and 43+/-6%, respectively (p<0.05 v. control). CONCLUSION: Our findings suggest that the reduction of alcohol content from 12% to 6% in wine did not alter its antioxidant and cardioprotective properties. Moderate and regular consumption of lower alcohol content wines may confer beneficial effects without the risks associated with traditional wines of higher alcohol content. PMID- 22668966 TI - Trauma and violence in the Later Stone Age of southern Africa. AB - BACKGROUND: Antemortem and perimortem fractures in skeletons recovered from Later Stone Age burials in southern Africa demonstrate that people were, on occasion, the victims of severe trauma attributable to interpersonal violence. METHODS: Case studies are presented of cranial vault depression fractures on 4 different individuals and a young adult female who had 2 bone arrowheads embedded in the lower vertebrae. These are compared with other cases from the literature. RESULTS: The evidence from the archaeological skeletons suggests that interpersonal violence was a regular occurrence among prehistoric foragers. Additional cases show healed fractures of other bones, but these probably represent injuries from day-to-day activities rather than violent conflict. DISCUSSION: The ethnographic depiction of the San as 'harmless people' is probably inaccurate, or, at best, only representative of the situation in northern Botswana in the 1960s. Damage to the bones indicates that the cause of the trauma was intentional violence. Explanatory models that suggest intense competition between hunter-gatherer groups are probably more accurate than ones that suggest that the groups were non-aggressive. CONCLUSION: Historical references to the San as aggressive and dangerous adversaries may be more accurate than revisionist historians have argued. PMID- 22668967 TI - Low acceptability of medical male circumcision as an HIV/AIDS prevention intervention within a South African community that practises traditional circumcision. AB - BACKGROUND: Traditional circumcision is practised among some indigenous tribes in South Africa (SA) such as the Xhosa. Recent experimental evidence has demonstrated the benefits of male circumcision for the prevention of HIV infection in heterosexual men. The acceptability of circumcision as a biomedical intervention mirroring an ingrained cultural practice, as well as the age and extent of the procedure, are poorly understood. METHODS: Men aged 15 - 42 years were recruited in a peri-urban settlement near Cape Town. Participants completed an interviewer-administered questionnaire assessing self-reported circumcision status, context and reasons for previous or planned circumcision, and willingness to undergo medical circumcision for themselves or their sons. Results were confirmed by clinical examination. The most recent HIV test result was compared with circumcision status. RESULTS: Of the 199 men enrolled, 148 (74%) reported being traditionally circumcised; of the 51 not circumcised, 50 were planning the traditional procedure. Among men self-reporting circumcision, 40 (27%) had some or all of the foreskin remaining. The median age at traditional circumcision was 21 years (interquartile range 19 - 22 years). While knowledge of the preventive benefit of circumcision was reported by 128 men (66%), most were unwilling to undergo medical circumcision or allow their sons to do so, because of religion/culture, notions of manhood, and social disapproval. CONCLUSION: Almost all men in this study had undergone or were planning to undergo traditional circumcision and were largely opposed to the medically performed procedure. In the majority, traditional circumcision had occurred after the mean age of sexual debut and almost a quarter were found to have only partial foreskin removal. To ensure optimal HIV prevention benefits, strategies to facilitate complete foreskin removal prior to sexual debut within traditional circumcision practices require further attention. PMID- 22668968 TI - Racial discrimination: experiences of black medical school alumni at the University of Cape Town, 1945 - 1994. AB - OBJECTIVE: Reflecting on its role during apartheid, the University of Cape Town (UCT) Faculty of Health Sciences undertook a study to explore the experiences of black alumni who trained in the period 1945 - 1994. DESIGN: Seventy-five black alumni were selected through purposive and snowball recruitment, resulting in 52 face-to-face and 23 telephonic or postal interviews. RESULTS: Experiences of racial discrimination were widely reported and respondents believed the quality of their training was adversely affected. Until 1985, black students were required to sign a declaration agreeing to excuse themselves from classes where white patients were present. Black students were denied access to white patients in wards, and the university admitted that it could not guarantee their clinical training. Tutorial groups were racially segregated. Black students were also excluded from university facilities, events and extramural activities. Themes that emerged were: lack of social contact with white staff and students during training, belief that white staff members actively or tacitly upheld discriminatory regulations, and resistance by black students. Efforts of some white staff to resist discrimination were acknowledged. CONCLUSION: Racism was entrenched explicitly and implicitly. Perceptions of the attitudes of white staff to apartheid legislation on the part of black alumni were diverse, ranging from claims of active support for racial discrimination to recognition of attempts to resist racist rules. These findings provided the basis for faculty transformation initiatives based on human rights, respect for human dignity and non discrimination. PMID- 22668969 TI - Access to livelihood assets among youth with and without disabilities in South Africa: implications for health professional education. AB - PURPOSE: This study compared access to 5 livelihood assets among disabled and non disabled youth, to inform health professionals on inequities related to disability and to monitor the transformation agenda aimed at creating an inclusive society. METHODS: Fieldworkers interviewed 989 youth (18 - 35 years; 523 (52.9%) disabled youth (DY), 466 (47.1%) non-disabled youth (NDY)) at 9 sites in 5 South African provinces. Descriptive statistics were used to describe demographic characteristics and livelihood assets. Chi-squared and t-tests were used for comparisons. RESULTS: Doctors at hospitals and nurses at clinics are health professionals most frequently seen. Far fewer DY than NDY attended and completed school. Unemployment was markedly more common among DY than among NDY. Barriers to accessing employment for DY were poor health and lack of skills development, and a lack of job opportunities for NDY. Both groups received the same amount of support from immediate household members, but significantly more NDY received support from extended family, friends, partners, and neighbours. They spent significantly more time engaging in all free-time activities. NDY reported more access to bathrooms, phone, and newspapers, as well as public services and the business sector. Participation and access were limited for both groups because of inaccessible public transport. CONCLUSION: This paper shows that DY have a greater struggle to access livelihood assets than non-disabled peers. The Disability Studies Academic Programme at the University of Cape Town is an initiative that seeks to take specific focused action with disability organisations in order to address the inequities faced by disabled youth to ensure their inclusion in development to the same degree as their non-disabled peers. PMID- 22668970 TI - Infant-parent psychotherapy at primary care level: establishment of a service. AB - BACKGROUND: Access to infant and child psychiatric care in South Africa is limited. With focus on maternal and infant mental health, early identification and management of developmental, behavioural and psychosocial parent-child problems can be initiated. OBJECTIVES: To establish a mental health service for children aged 0 - 3 years, for delivery of infant-parent psychotherapy in a community setting. METHODS: The DC: 0-3R Classification for Mental Health and Development Disorders of Infancy and Early Childhood was used for diagnosis and standard multi-modal parent-infant psychotherapy methods for short-term interventions. RESULTS: A total of 179 infants and their maternal caregivers were seen. The primary referral symptom was faltering weight. The most frequent psychiatric diagnosis made was 'feeding disorder of caregiver-infant reciprocity'. Seventy two per cent of caregivers were exposed to more than 4 stress factors; 75% proved compliant with treatment with resultant improvement in the relationship between caregiver and child (78%) and in the age-appropriated functioning of the infant (76%). CONCLUSION: This study confirms that a psychotherapeutic service for infants and mothers can be established at a primary healthcare level. Infant-parent psychotherapy was effective and readily accepted by the community. This service offers a training model for mental health providers enabling early recognition of mental health problems in children and psychotherapeutic intervention. PMID- 22668972 TI - Proximal cerebral arteries develop myogenic responsiveness in heart failure via tumor necrosis factor-alpha-dependent activation of sphingosine-1-phosphate signaling. AB - BACKGROUND: Heart failure is associated with neurological deficits, including cognitive dysfunction. However, the molecular mechanisms underlying reduced cerebral blood flow in the early stages of heart failure, particularly when blood pressure is minimally affected, are not known. METHODS AND RESULTS: Using a myocardial infarction model in mice, we demonstrate a tumor necrosis factor-alpha (TNFalpha)-dependent enhancement of posterior cerebral artery tone that reduces cerebral blood flow before any overt changes in brain structure and function. TNFalpha expression is increased in mouse posterior cerebral artery smooth muscle cells at 6 weeks after myocardial infarction. Coordinately, isolated posterior cerebral arteries display augmented myogenic tone, which can be fully reversed in vitro by the competitive TNFalpha antagonist etanercept. TNFalpha mediates its effect via a sphingosine-1-phosphate (S1P)-dependent mechanism, requiring sphingosine kinase 1 and the S1P(2) receptor. In vivo, sphingosine kinase 1 deletion prevents and etanercept (2-week treatment initiated 6 weeks after myocardial infarction) reverses the reduction of cerebral blood flow, without improving cardiac function. CONCLUSIONS: Cerebral artery vasoconstriction and decreased cerebral blood flow occur early in an animal model of heart failure; these perturbations are reversed by interrupting TNFalpha/S1P signaling. This signaling pathway may represent a potential therapeutic target to improve cognitive function in heart failure. PMID- 22668973 TI - 3,5-Dicaffeoylquinic acid isolated from Artemisia argyi and its ester derivatives exert anti-leucyl-tRNA synthetase of Giardia lamblia (GlLeuRS) and potential anti giardial effects. AB - An aqueous ethanol extract of Artemisia argyi inhibited the aminoacylation activity of LeuRS from Giardia lamblia (GlLeuRS). The bioassay-guided fractionation of the extract led to the isolation of 3,5-dicaffeoylquinic acid (1), with an IC50 of 5.82 MUg/mL. The ester derivatives of 1 were also found to possess strong anti-GlLeuRS effects, with IC50 values of 1.79, 5.51 and 2.56 MUg/mL respectively. Anti-giardial assay showed that the derivatives, especially 3,5-dicaffeoylquinic acid propyl ester (4) (IC50=4.62 MUg/mL), were effective at killing G. lamblia. PMID- 22668974 TI - Berberine increases the expression of NHE3 and AQP4 in sennosideA-induced diarrhoea model. AB - Berberine, a compound isolated from Chinese Goldthread Rhizome, has been widely used as a non-prescription drug to treat diarrhoea in China. Previous studies have demonstrated multiple pharmacological activities for berberine, including its significant role in antimicrobial activity. However, its effect on ion exchange and water transfer remains unclear. The present study aims to explore the effect of berberine on the expression of Na(+)/H(+) exchanger3 (NHE3) and aquaporin4 (AQP4) in both diarrhoea mouse model induced by sennosideA and human intestinal epithelium cell line (HIEC). Semi-quantitative RT-PCR, immunohistochemistry and western blotting were adopted to detect the mRNA and protein expression levels of NHE3 and AQP4. Furthermore, the absorption of berberine and the PKC activity were detected by HPLC and PepTag(r) Assay to elucidate the underlying mechanisms. It was shown that the expression levels of NHE3 and AQP4 were significantly increased in the diarrhoea mice treated with berberine compared with the untreated diarrhoea mice. Similarly, the expression levels of NHE3 and AQP4 were strikingly enhanced in HIEC co-treated with sennosideA and berberine compared with samples treated with sennosideA only. We also found the maximal absorption of berberine to be approximately 0.01%. In addition, no significant change of PKC activity was observed in the different HIEC treated groups. These results showed that berberine was able to increase the expression of NHE3 and AQP4, suggesting that berberine might exhibit its anti diarrhoeal effect partially by enhancing the absorption of Na(+) and water. PMID- 22668975 TI - The applicability of ganglion cell complex parameters determined from SD-OCT images to detect glaucomatous eyes. AB - PURPOSE: To determine whether the thicknesses of the different parameters of the ganglion cell complex (GCC) and peripapillary retinal nerve fiber layer can be used to differentiate eyes with glaucoma from normal eyes. METHODS: Two hundred sixty-one eyes, including 68 normal eyes and 32 preperimetric glaucoma, 81 early glaucoma, and 80 advanced glaucoma were analyzed in the present study. The thicknesses of the GCC and retinal nerve fiber layer were measured using RTVue spectral-domain optical coherence tomographic (SD-OCT) images. The area under the receiver operating characteristic (AUROC) curve and sensitivities at fixed specificities were calculated for each parameter. A logistic regression analysis was used to determine the risk factors for glaucoma. RESULTS: The 2 largest AUROC curves for all glaucoma stages were those for the GCC parameters. The global loss volume (GLV) was always one of the 2 highest values of the AUROC curve. The GLV also had the highest sensitivity at a fixed specificity to identify glaucoma at early and advanced stage. The focal loss volume (FLV) had the largest AUROC curve value and the highest sensitivity at a fixed specificity for advanced glaucoma. The logistic regression analysis showed that the GLV was one of the factors that predicted preperimetric glaucoma [odds ratio (OR)=1.74] and early glaucoma (OR=1.22), whereas the FLV was useful for detecting advanced glaucoma (OR=2.32). CONCLUSIONS: The SD-OCT-derived macular GCC parameters can be used to detect preperimetric and perimetric glaucoma. The new GCC parameters, GLV and FLV, performed well in discriminating glaucomatous eyes from normal eyes. PMID- 22668976 TI - An alternative approach for management of delayed suprachoroidal hemorrhage after glaucoma procedures. AB - PURPOSE: To introduce an alternative approach for management of delayed suprachoroidal hemorrhage (DSCH) after intraocular procedures, and to report the outcomes of such intervention in a consecutive series of patients. METHODS: This interventional case series reports consecutive cases of DSCH after glaucoma procedures, managed with a different approach. Instead of the usual 7 to 14 days observation period for clot lysis, the hemorrhage was drained from the suprachoroidal space immediately after diagnosis. Outcome measures included visual acuity and intraocular pressure. RESULTS: Seven eyes of 7 patients including 4 men and 3 women, with mean age of 42.6+/-29.6 years with DSCH were enrolled. Immediately after the diagnosis, choroidal tap and anterior chamber reformation were performed for all patients and followed for 21.4+/-13.4 months. Intraocular pressure decreased significantly after intervention (P=0.01). The mean final visual acuity improved significantly to 1.09+/-0.31 logarithm of minimum angle of resolution (LogMAR) (P=0.003). CONCLUSIONS: It seems that surgical drainage immediately after the diagnosis of DSCH can be considered as an alternative to the more conservative approach. PMID- 22668977 TI - Anterior segment changes after pilocarpine and laser iridotomy for primary angle closure suspects with Scheimpflug photography. AB - PURPOSE: To assess changes in Scheimpflug-based measurements of the anterior segment after pilocarpine administration and prophylactic laser peripheral iridotomy in narrow anterior chamber angles. METHODS: Thirty-seven eyes in 37 patients with occludable angles were included in this prospective interventional case series. Primary angle-closure suspects (iridotrabecular contact in 3 quadrants or more) were enrolled. Patient evaluation included indentation gonioscopy, Goldmann tonometry, and optic nerve examination. The mean of 3 consecutive Pentacam measurements was taken at baseline, 45 minutes after 2% pilocarpine administration, and 1 month after laser peripheral iridotomy (LPI). Anterior chamber angle (ACA), anterior chamber volume (ACV), anterior chamber depth (ACD), pupil diameter, central corneal thickness, and intraocular pressure were measured. RESULTS: ACV increased significantly after LPI (from a mean +/- standard error of 94.6 +/- 3.6 mm(3) to 108.8 +/- 3.4 mm(3), P<0.001), as did the ACA (26.7 +/- 0.9 degrees to 28.2 +/- 0.8 degrees, P<0.001). Central corneal thickness decreased significantly after LPI (558.1 +/- 5.3 MUm to 552.6 +/- 5.7 MUm, P=0.018). Central ACD increased slightly after LPI, but this was not statistically significant (2.13 +/- 0.05 mm to 2.15 +/- 0.05 mm, P=0.109). Pupil diameter and intraocular pressure also did not change significantly after LPI. After pilocarpine, the ACV decreased significantly (by 4.3 +/- 1.3 mm(3), P=0.009), as did the central ACD (by 0.1 +/-0.02 mm, P<0.001) and the pupil diameter (by 0.74 +/- 0.06 mm, P<0.001). CONCLUSIONS: Scheimpflug photography demonstrates significant anterior segment changes after pilocarpine and after LPI in primary angle-closure suspects. PMID- 22668978 TI - The effect of selective laser trabeculoplasty on aqueous humor dynamics in patients with ocular hypertension and primary open-angle glaucoma. AB - PURPOSE: To investigate the effect of primary selective laser trabeculoplasty (SLT) on outflow facility and aqueous flow rate in patients with primary open angle glaucoma or ocular hypertension. METHODS: Eighteen eyes (9 with ocular hypertension and 9 with primary open-angle glaucoma) were included in this prospective noncontrolled study. Patients with intraocular pressures (IOPs)>21 to 35 mm Hg were treated with 360-degree SLT after a baseline measurement of IOP, tonographic outflow facility, and morning aqueous humor production. Electronic Schiotz tonography was used to measure the outflow facility. The aqueous flow rate was measured by fluorophotometry, and a pneumotonometer was used to measure the IOP. All measurements were repeated at least 3 months after the laser therapy. Paired Student t tests were used to compare aqueous dynamics parameters before and after treatment. RESULTS: The mean age of the study population was 56.7 +/- 12.4 years. The IOP decreased significantly (21%) from 24.0 +/- 3.0 to 18.9 +/- 2.7 mm Hg (P<0.001), whereas tonographic outflow facility increased significantly (55.5%) from 0.09 +/- 0.05 to 0.14 +/- 0.08 uL/min/mm Hg (P=0.003) 3 months after laser treatment. No statistically significant changes in the production of aqueous humor were found (P=0.46). CONCLUSIONS: Our results show that SLT lowers the IOP by increasing the outflow through the trabecular meshwork, but it has no significant effect on the aqueous flow rate. PMID- 22668979 TI - Glaucoma tube imaging using anterior segment optical coherence tomography in patients with opaque cornea. AB - PURPOSE: Anterior segment optical coherence tomography (AS-OCT) was used to diagnose Ahmed tube tip patency in patients with opaque corneas after corneal transplantation and tube shortening. MATERIALS AND METHODS: Noncomparative observational case series: 3 consecutive patients with nonvisualized tubes and uncontrolled intraocular pressure after corneal transplantation underwent AS-OCT to determine tube tip patency. RESULTS: In each case, AS-OCT allowed for imaging of the tube position, wall passage, and osteum patency that could not be visualized on gonioscopy. Two of 3 tubes were found to be nonpatent. CONCLUSIONS: High-resolution noncontact cross-sectional AS-OCT images provide information on tube position and patency in the presence of opaque media after corneal transplantation, assisting with clinical decision-making. PMID- 22668980 TI - Ability of optical coherence tomography-determined ganglion cell complex thickness to total retinal thickness ratio to diagnose glaucoma. AB - PURPOSE: To evaluate the usefulness of the spectral-domain optical coherence tomography (SD OCT)-determined ganglion cell complex thickness to total retinal thickness ratio (G/T ratio) in diagnosing glaucoma. METHODS: A total of 99 eyes with primary open-angle glaucoma and 35 normal eyes were enrolled in the study. SD OCT (RTVue-100) was used to measure the macular ganglion cell complex thickness, total retinal thickness, outer retinal thickness, and circumpapillary retinal nerve fiber layer (RNFL) thickness. A new macular parameter, the G/T ratio, was also calculated. The ability of each parameter to diagnose glaucoma was examined by analyzing the area under the receiver operating characteristics curve (AUROC) and the sensitivity at fixed specificity. RESULTS: The G/T ratio was 36.0 +/- 1.5% in normal eyes, 31.8 +/- 1.7% in early glaucoma, and 30.2 +/- 2.6% in advanced glaucoma. These decreases in the ratio were statistically significant. For the AUROC, the individual SD OCT parameters were 0.982 for the G/T ratio, 0.968 for the macular ganglion cell complex thickness, 0.942 for the RNFL thickness, and 0.841 for the total retinal thickness. The AUROC for the G/T ratio was significantly higher than that seen for the total retinal and RNFL thicknesses (P<0.05). Analyses of the sensitivity at a specificity of >90% indicated that the G/T ratio (sensitivity, 93.94%) was the best diagnostic parameter. CONCLUSIONS: Decreases in the G/T ratio occur during the early stages of glaucoma. When using SD OCT to diagnose glaucoma, the G/T ratio may improve the diagnostic ability of the macular parameter. PMID- 22668981 TI - Intraocular pressure fluctuation in patients with primary open-angle glaucoma combined with high myopia. AB - PURPOSE: To investigate whether patients with primary open-angle glaucoma combined with high myopia (POAG-HM) have short-term intraocular pressure (IOP) fluctuations at resting conditions over 24 hours and after dynamic exercise. METHODS: Prospective Control Clinical Study. Eighty eyes of 80 high-tension Chinese POAG patients only on prostaglandin analog locally were categorized as per their degree of myopia (myopes 6 D or more, n=30 and between -0.76 and -5.99 D, n=29) or without myopia (n=21). Twenty-four-hour IOP fluctuations at resting conditions were observed in protocol 1, and IOP fluctuations after 10-minute exercise at 20% maximum Watt (Wmax) and followed by 5 minutes of exercise at 60% Wmax were observed in protocol 2. RESULTS: Twenty-four-hour IOP fluctuations at resting conditions were not statistically significant among groups (P=0.58). After 10 minutes of moderate (20% Wmax) exercise, patients with POAG-HM had significant IOP decrease (3.50+/-2.76 mm Hg) over other subjects (analysis of covariance, age, as a covariate, was controlled, P=0.02). After 5 minutes of heavy (60% Wmax) exercise, patients with POAG-HM had significantly a greater postexercise IOP decrease (7.57+/-3.47 mm Hg) than other groups (P=0.00). CONCLUSIONS: High-tension POAG patients with high myopia on only pharmacological glaucoma therapy have significantly greater IOP fluctuations after moderate and heavy exercise and do not have greater 24-hour IOP fluctuations at resting conditions. PMID- 22668982 TI - Measurement of subfoveal choroidal thickness in normal-tension glaucoma in Korean patients. AB - PURPOSE: To evaluate subfoveal choroidal thickness (CT) in eyes with normal tension glaucoma (NTG) in patients who were visualized by enhanced depth imaging optical coherence tomography. METHODS: In this observational, comparative case series, subfoveal CT was measured with enhanced depth imaging optical coherence tomography in 35 eyes of normal individuals and 32 eyes of patients with NTG. Subfoveal CT in each eye was analyzed by measuring the vertical distance from Bruch membrane to the innermost sclera layer. RESULTS: The mean subfoveal CT in the normal individual group and the NTG patient group were 300.0+/-52.7 and 289.5+/-100.4 um, respectively. There was no difference in subfoveal CT in the 2 groups (P=0.60). The mean subfoveal CT in all subjects was significantly correlated negatively with age only (P=0.03). CONCLUSIONS: The subfoveal CT does not differ between the eyes of the normal individual group and the eyes in the NTG patient group, suggesting that CT may not play a role in the pathogenesis of NTG. PMID- 22668983 TI - Risk calculation variability over time in ocular hypertensive subjects. AB - PURPOSE: To investigate the longitudinal variability of glaucoma risk calculation in ocular hypertensive (OHT) subjects. METHODS: We reviewed the charts of untreated OHT patients followed in a glaucoma referral practice for a minimum of 60 months. Clinical variables collected at baseline and during follow-up included age, central corneal thickness (CCT), intraocular pressure (IOP), vertical cup-to disc ratio (VCDR), and visual field pattern standard deviation (VFPSD). These were used to calculate the 5-year risk of conversion to primary open-angle glaucoma (POAG) at each follow-up visit using the Ocular Hypertension Treatment Study and European Glaucoma Prevention Study calculator (http://ohts.wustl.edu/risk/calculator.html). We also calculated the risk of POAG conversion based on the fluctuation of measured variables over time assuming the worst case scenarios (final age, highest PSD, lowest CCT, highest IOP, and highest VCDR) and best case scenarios (baseline age, lowest PSD, highest CCT, lowest IOP, and lowest VCDR) for each patient. Risk probabilities (%) were plotted against follow-up time to generate slopes of risk change over time. RESULTS: We included 27 untreated OHT patients (54 eyes) followed for a mean of 98.3+/-18.5 months. Seven individuals (25.9%) converted to POAG during follow-up. The mean 5-year risk of conversion for all patients in the study group ranged from 2.9% to 52.3% during follow-up. The mean slope of risk change over time was 0.37+/-0.81% increase/y. The mean slope for patients who reached a POAG endpoint was significantly greater than for those who did not (1.3+/-0.78 vs. 0.042+/ 0.52%/y, P<0.01). In each patient, the mean risk of POAG conversion increased almost 10-fold when comparing the best case scenario with the worst case scenario (5.0% vs. 45.7%, P<0.01). CONCLUSIONS: The estimated 5-year risk of conversion to POAG among untreated OHT patients varies significantly during follow-up, with a trend toward increasing over time. Within the same individual, the estimated risk can vary almost 10-fold based on the variability of IOP, CCT, VCDR, and VFPSD. Therefore, a single risk calculation measurement may not be sufficient for accurate risk assessment, informed decision-making by patients, and physician treatment recommendations. PMID- 22668984 TI - Clear lens extraction in plateau iris with bilateral acute angle closure in young. AB - PURPOSE: We report resolution of bilateral angle closure in a young patient with plateau iris following clear lens extraction METHODS: A 30 year old female presented with bilateral angle closure. RESULT: After a failed attempt of laser iridotomy, there was immediate resolution of angle closure following clear lens extraction by phacoemulsification and intraocular lens implantation. Postoperative ultrasound biomicroscopy identified anteriorly rotated ciliary processes in both eyes. CONCLUSIONS: This case report highlights the role of therapeutic clear lens extraction in angle closure due to plateau iris. PMID- 22668985 TI - Clinical outcomes of combined anterior and posterior spinal fusion for dystrophic thoracolumbar spinal deformities of neurofibromatosis-1: fate of nonvascularized anterior fibular strut grafts. AB - STUDY DESIGN: Retrospective study. OBJECTIVE: To analyze the clinical outcomes of anterior and posterior spinal fusion (APSF) using a fibular strut autograft (FSAG) and to investigate the morphological changes in the reconstructed spinal column of dystrophic deformities in neurofibromatosis (NF)-1. SUMMARY OF BACKGROUND DATA: APSF is desirable for dystrophic deformities in NF-1 with more than 50 degrees of dystrophic kyphosis. There are few reports regarding the clinical outcomes of APSF in which the morphological changes over time of the anterior strut graft have been investigated. METHODS: The clinical and radiographic outcomes of APSF with FSAG were investigated in 10 consecutive patients with dystrophic deformity in NF-1. For qualitative and quantitative analyses, the chronological changes in the FSAG configuration, length, and diameter were evaluated. RESULTS: The mean follow-up period was 9 years, 9 months (range, 1-30 years). Graft bone erosion and postoperative curve progression were not observed in any patient. In quantitative analyses of the anterior strut, the mean ratio of the latest and immediately postoperative FSAG lengths was 0.98 (0.93-1.09). The mean central/peripheral ratios of the FSAG diameter (central portion/[upper end + lower end]/2) were 1.02 (0.92-1.10) immediately after surgery, and 1.01 (0.92-1.07) at the latest follow-up, with no significant change between these 2 time points (P = 0.937). The mean preoperative cross-sectional area of the apical vertebral body and its mean virtual cross-sectional area at the final follow-up were 3.80 (1.83-5.43) and 4.87 (2.46-7.00) cm(2), respectively, with a significant difference between these 2 parameters (P = 0.0078). The mean final/preoperative ratio was 1.31 (1.10-1.43). CONCLUSION: APSF with FSAG for dystrophic deformity in NF-1 successfully reconstructed a reliable spinal column with a rich bone stock. The FSAG and surrounding vertebral bodies were free from postoperative erosion due to dystrophic changes and maintained their stability for a long time. PMID- 22668986 TI - To the other side of the neglected brain: the hyperexcitability of the left intact hemisphere. AB - The human brain is characterized by the lateralization of cognitive functions. Multiple lines of evidence suggest the deployment of visuospatial attention is controlled by a frontoparietal network, with a right hemisphere dominance. Among cortical areas included in the network, the right posterior parietal cortex (PPC) has been proposed to be a crucial node and has also been implicated on clinical grounds. Here, the authors provide an overview of the existent literature giving evidence to a functional asymmetry of the parietal cortices in directing visuospatial attention, focusing on those studies seeking to characterize the causal role of PPC, applying transcranial magnetic stimulation and its combination with imaging techniques, such as electroencephalography and fMRI. First, the role of PPC and how this region exerts its control over remote areas of both hemispheres is discussed. The second part discusses studies involving neglect patients shedding light on the complex interplay between left and right PPC, strongly supporting the hemispheric rivalry theory. Finally, studies demonstrating changes of neglect disorders following the manipulation of the unaffected hemisphere activation will be discussed. PMID- 22668987 TI - Hypothalamic kiss1 mRNA and kisspeptin immunoreactivity are reduced in a rat model of polycystic ovary syndrome (PCOS). AB - An intact hypothalamic kiss1/kisspeptin/kiss1r complex is a prerequisite for reproductive competence, and kisspeptin treatment could be a practical therapeutic approach to some problems of infertility. One such disorder is polycystic ovarian syndrome (PCOS), a common cause of infertility affecting more than 100 million women. A rodent model of PCOS is the prepubertal female rat treated for a prolonged period with dihydrotestosterone (DHT), which induces many of the metabolic characteristics of the syndrome. We hypothesized that hypothalamic kiss1 mRNA levels, and kisspeptin immunoreactivity (ir), would be abnormal in these rats. Prepubertal female rats were exposed to DHT for 60 days. Rats were killed in two groups: at 26 and 60 days of DHT exposure. Kiss1 mRNA was quantified in hypothalamus, pituitary, ovary and visceral adipose tissue. Separate groups of rats provided brain tissue for immunohistochemical analysis of kisspeptin-ir. At 26 days of DHT exposure, hypothalamic kiss1 mRNA was severely depleted. In contrast DHT had no effect on pituitary kiss1 expression but it significantly increased levels of kiss1 mRNA in fat (+9-fold; p<0.01) and in ovary (+3-fold; p<0.05). At 60days, kiss1 expression had reverted to normal in hypothalamus and ovary but remained elevated in fat (+4-fold; p<0.05). Immunohistochemical analysis revealed that after 26 days of exposure to DHT, kisspeptin-ir was almost completely absent in the arcuate nucleus and a large depletion in kisspeptin +ve fibers was also seen in the paraventricular nucleus, supraoptic nucleus and in the anteroventral periventricular area. At 60 days, despite restored normal levels of kiss1 mRNA, hypothalamic kisspeptin-ir remained depleted in the treated rats. In summary Kiss1 gene expression is differentially affected in various tissues by chronic exposure to dihydrotestosterone in a rat model of polycystic ovary syndrome. In hypothalamus, specifically, kiss1 mRNA, and levels of kisspeptin immunoreactivity, are significantly reduced. Since these rats exhibit many of the characteristics of polycystic ovary syndrome, we suggest that atypical kiss1 expression may contribute to the multiple tissue abnormalities observed in women with this disorder. However, and of some importance, our data do not appear to be consistent with the elevated levels of LH seen in women with PCOS; i.e. reduced levels of hypothalamic kiss1 mRNA and kisspeptin immunoreactivity observed in DHT-treated rats are unlikely to produce elevated LH secretion. PMID- 22668989 TI - Harborview Medical Center. Foreword. PMID- 22668988 TI - Can the default-mode network be described with one spatial-covariance network? AB - The default-mode network (DMN) has become a well accepted concept in cognitive and clinical neuroscience over the last decade, and perusal of the recent literature attests to a stimulating research field of cognitive and diagnostic applications (for example, (Andrews-Hanna et al., 2010; Koch et al., 2010; Sheline et al., 2009a; Sheline et al., 2009b; Uddin et al., 2008; Uddin et al., 2009; Weng et al., 2009; Yan et al., 2009)). However, a formal definition of what exactly constitutes a functional brain network is difficult to come by. In recent contributions, some researchers argue that the DMN is best understood as multiple interacting subsystems (Buckner et al., 2008) and have explored modular components of the DMN that have different functional specialization and could to some extent be identified separately (Fox et al., 2005; Uddin et al., 2009). Such conception of modularity seems to imply an opposite construct of a 'unified whole', but it is difficult to locate proponents of the idea of a DMN who are supplying constraints that can be brought to bear on data in rigorous tests. Our aim in this paper is to present a principled way of deriving a single covariance pattern as the neural substrate of the DMN, test to what extent its behavior tracks the coupling strength between critical seed regions, and investigate to what extent our stricter concept of a network is consistent with the already established findings about the DMN in the literature. We show that our approach leads to a functional covariance pattern whose pattern scores are a good proxy for the integrity of the connections between a medioprefrontal, posterior cingulate and parietal seed regions. Our derived DMN network thus has potential for diagnostic applications that are simpler to perform than computation of pairwise correlational strengths or seed maps. PMID- 22668990 TI - Pioneers in trauma care at Harborview Medical Center. AB - Harborview Medical Center in Seattle has been home to the pioneering work of University of Washington (UW) Medicine physicians and staff who have led innovations to improve trauma care for more than 40 years. As the only level I adult and pediatric trauma center and regional burn center for Washington, Alaska, Montana, and Idaho, Harborview provides cares for more than 6500 critically injured trauma and burn patients per year. Our physicians, researchers and staff are recognized as national experts and as collaborative partners with nursing in the delivery of outstanding clinical care, research, and education. Beginning with the establishment of Seattle Medic One in the late 1960s, a groundbreaking program to train firefighters as paramedics, Harborview and the work of UW Medicine has been recognized locally and globally as a leader in every component of the ideal trauma system, as defined by the American College of Surgeons: prevention, access, acute hospital care, rehabilitation, education, and research activities. PMID- 22668991 TI - Implementation of TeamSTEPPS in the emergency department. AB - Team training and practice is an essential part of emergency department workflow. TeamSTEPPS (Team Strategies and Tools to Enhance Performance and Patient Safety) is a teamwork and communication systems model that has the potential to improve patient safety while also addressing aspects of staff satisfaction and morale. This article describes the experience of one emergency department's implementation of TeamSTEPPS, with a focus on methods of training faculty and staff, progression of implementation over a period of time, and evaluation of the process with recommendations for future growth. Background, history, and specific tools used within the department are described, with an emphasis on "briefs," "huddles," and "debriefs" or team "wrap-ups." PMID- 22668992 TI - Conducting a multidisciplinary morbidity and mortality conference in the trauma surgical intensive care unit. AB - The trauma-surgical intensive care unit at Harborview Medical Center has developed a multidisciplinary case review process to allow discussion of complications and issues in an open forum among multiple services. Conducted monthly, this meeting provides a forum for clear communication between members of the patient care team with the goal of developing best practices, system changes, and policies that will minimize risk for the patients and provide education for the staff. PMID- 22668993 TI - Partnering with family members to improve the intensive care unit experience. AB - Family members play an important and varied role in a patient's health care experience, ranging from emotional support to surrogate health care decision making. The family role can be substantial in the intensive care unit setting, as the patients rely upon family members to make health care decisions for them. The core components of patient- and family-centered care include information sharing, a welcoming environment, respect for individual values and needs, comfort and support, and providing a helpful framework for developing a productive partnership with family members. Involving family members in daily operations and providing services that make it easier for family members to participate in the care process result in the best possible care for their loved one. Including the family perspective in quality improvement initiatives better ensures that any changes made will result in better care for future patients and family members. PMID- 22668994 TI - The role of palliative care in trauma. AB - Trauma remains a leading cause of morbidity and mortality in the United States. Despite the aggressive and heroic nature of trauma care, including trauma surgery, 10% to 20% of patients admitted to trauma intensive care units die. As the population continues to age, it is predicted that by 2050, approximately 40% of those experiencing traumatic injury will be older than 65 years. For multiple reasons, people in this age group who experience trauma are at greater risk for death. Palliative care is the specialty of health care that provides care for patients with serious, life-threatening, or life-limiting illness or injury, regardless of the stage of disease or treatment. The goal of palliative care is to reduce or alleviate suffering through expert pain and symptom management, as well as assistance with decision making. The integration of palliative and trauma care can assist and support patients and families through stressful, often life changing times, regardless of the final outcome. PMID- 22668995 TI - Evaluating culture practices used to identify infection in patients with brain injury. AB - The neurosurgical intensive care unit staff at Harborview Medical Center, Seattle, Washington, had a strong desire to implement strategies to lower temperatures in their patients with brain injury because the patients with elevated temperatures often have lower Glasgow Coma Scores. In addition, neurologic improvement was demonstrated when high temperatures were lowered. Hospital policy dictated that temperatures be allowed to climb to more than 38.5 degrees C before treatment because this temperature was used as the trigger for culture collection every 24 hours. The expressed rationale was that temperature management would obscure the trigger and infections would be missed. Thus, the investigators wanted to determine whether temperature elevation was a reliable indicator of infection. A quality improvement tool was developed, and the patient populations to be evaluated were those admitted with the diagnosis of subarachnoid hemorrhage, arteriovenous malformation, or traumatic brain injury. The number of times each patient was cultured and whether he or she was cultured because of temperature, a white blood cell count elevation, or clinical indicators were tracked. Findings showed that the use of temperature as a screening indicator for infection produced few positive cultures and that the practice of daily cultures yielded few positive results generally. Conclusions made from the data were that temperature is not an accurate indicator of infection in these patients with brain injury and fever management would not adversely impact infection identification. Policy within the Neuroscience intensive care unit was changed to reflect these findings. PMID- 22668996 TI - Rehabilitation starts in the intensive care unit. AB - Each year between 10 000 and 12 000 spinal cord injuries occur in the United States. Once injured, many of these patients will receive a portion of their care in an intensive care unit (ICU), where their treatment will begin. Harborview Medical Center in Seattle, Washington, provides comprehensive care to approximately 60 to 70 cervical spinal cord injuries each year. Because of many factors such as hemodynamic instability, pulmonary complications, and risk of infection, patients with cervical spinal cord injuries can spend up to 2 or more weeks in the ICU before they transfer to a rehabilitation unit. To achieve optimal outcomes, it is imperative that members of the interdisciplinary team work together in a consistent, goal-oriented, collaborative manner. This team includes physicians, nurses, respiratory therapists, physical and occupational therapists, speech pathologists, dieticians, and rehabilitation psychologists. An individual plan is developed for each patient and rehabilitation starts in the ICU as soon as the patient is medically stable. This article will highlight the management strategies used in the neuroscience ICU at Harborview Medical Center and will include a case study as an example of the typical experience for our patients with high cervical cord injury. PMID- 22668997 TI - Infection control for critically ill trauma patients: a systematic approach to prevention, detection, and provider feedback. AB - Critically ill patients are particularly at risk for developing hospital-acquired infections. An understanding of the predisposing factors, the epidemiology of disease, and guidelines to treat and to prevent hospital-acquired infections is necessary to incorporate infection control into the daily care of the critically ill trauma patient. Although it remains a challenge, infection control programs have moved from providing surveillance data and guidelines recommendations to implementation and engagement programs aimed at a shared responsibility for hospital-acquired infections prevention. We describe a multidisciplinary approach to infection control in the critically ill trauma patient with a special focus on ventilator-associated pneumonia at a level 1 trauma and burn center. PMID- 22668998 TI - Retrospective review of the reduction of oral pressure ulcers in mechanically ventilated patients: a change in practice. AB - Hospital-acquired pressure ulcers (HAPU) are a growing concern in patient care. Mucosal pressure ulcers (PUs) on the lips, mouth, gums, and tongue caused by oral intubation and their securement devices can be difficult to identify and prevent. In an effort to address this problem and reduce mucosal PU, implementation of an alternative securement device, the Hollister ETAD endotracheal (ET) tube securing device, in conjunction with the B&B Medical Universal Bite Block, was introduced at our institution, a level 1 trauma and burn center, in July 2007. The ETAD was later replaced by the Hollister AnchorFast ET tube securing device in December 2007. By April 2009, they became the standard devices and method used to secure oral ET tubes. We hypothesized the use of the new securement devices and bite block would lead to a decrease of HAPUs on the lips, mouth, gums, and tongue of orally intubated critical care patients because these allow for better oral assessment and ET tube manipulation to redistribute pressure. Using data collected from our electronic medical record and our HAPU incidence tracking system, we analyzed the number of PUs on the lips, mouth, gums, and tongue of orally intubated patients in our preintervention (phase 1) group compared with the data from our postintervention (phases 2 and 3) groups. A clinically significant decrease in the reported incidence of HAPUs on the lips, mouth, gums, and tongue was noted in our phases 2 and 3 groups following introduction of the ETAD, AnchorFast, and Universal Bite Block in our institution. PMID- 22668999 TI - New paradigm in nutrition support: using evidence to drive practice. AB - Adequate nutrition support is a key component in achieving favorable outcomes for the critically ill patient. Significant evidence supports starting enteral nutrition rather than parenteral nutrition as early as possible after injury to promote positive outcomes. Evidence shows that enteral nutrition improves patient outcomes and decreases intensive care unit length of stay by improving splanchnic blood flow, moderating the metabolic response, sustaining gut integrity, and preventing bacterial translocation from the gut to the bloodstream. Implementing early enteral nutrition can be challenging. This article describes the rationale for early enteral nutrition, the evidence that favors enteral nutrition over parenteral nutrition, barriers to delivery of full enteral nutrition, and an evidence-based protocol developed at Harborview Medical Center to promote appropriate support. The role of the registered dietitian on the health care team in facilitating appropriate feeding is discussed. In addition, we will describe emerging nutrition therapies including the use of antioxidants, addition of the amino acid glutamine, use of immune-enhancing enteral formulas, and the potential role of probiotics that show promise in improving patient outcome. PMID- 22669000 TI - Multidisciplinary approach to improving pain management. AB - On a 30-bed trauma surgical unit in an academic medical center, a best practice group was established. For a first project, we worked on improving the patient's pain experience. The decision was driven by the units Hospital Consumer Assessment of Health Providers and Systems (HCAHPS) pain scores. We had consistently been in the 1st percentile whereas best practice hospital scores were in the 68th percentile for pain. In addition, patients were expressing dissatisfaction with pain care during wound care with physicians. We reviewed the HCAHPS scores and brainstormed possible factors leading to patients' dissatisfaction with their pain care. Staff developed a teaching tool, which included a communication plan for the individual patient's pain plan. Next, we addressed the wound care with the trauma surgeons to develop a better understanding of the problem and identify a solution. The best practice group collaboration meeting became a springboard to address the pain issue for surgical patients through their hospital stays. The nurse manager, educator, pain relief attendant, anesthesia attendant, and 2 trauma surgeons met to discuss how to improve the surgical patient's pain experience. This trauma surgical unit now exceeds the top performers in HCAHPS scores. We have moved from the 1st percentile to the 90th percentile in 5 months. PMID- 22669001 TI - Care for the patient with burns in the trauma rehabilitation setting. AB - Caring for patients who are recovering from severe burns is not common in most rehabilitation settings. Nursing challenges include patients' physical and psychological changes and their high care demands. Harborview Medical Center, a regional level 1 burn and trauma center in Seattle, Washington, accepted these nursing challenges and developed a successful plan of care consistent with current evidence. This article describes Harborview Medical Center's trauma rehabilitation nursing experiences while caring for patients with burns. Our experiences may assist other rehabilitation units that serve patients with burns. Says one burn survivor: "Nurses make a huge difference in recovery, as they are there 24 hours a day. It is their touch, their caring, and their listening that aid the patient in his journey from fire victim to burn survivor." PMID- 22669002 TI - Prehospital airway management: high tech meets trauma: an air medical perspective. AB - Trauma is the leading cause of death in the United States for those younger than 35 years and injuries sustained from trauma are a significant source of moderate to severe disability. The inability to establish, secure, or maintain a definitive airway is a major cause of preventable death and secondary injury due to inadequate oxygenation and ventilation. Prehospital airway management is an essential skill of any prehospital care provider. A critical component to providing excellent airway management is the ability of the provider to quickly establish endotracheal intubation without complications such as hypoxia, hyper/hypocapnea, or hypotension. These complications have been shown to cause increased morbidity and mortality, especially in patients suffering from traumatic brain injury. This article presents some of the challenges faced by flight nurses in the air medical environment and how Airlift Northwest has developed a structured, standardized approach to airway management both in training and it the prehospital setting. We will discuss the process improvements that lead to the implementation of video laryngoscopy as our first-line intubation tool. The ultimate goal of any air medical or prehospital emergency medical services program is to manage 100% of airways without complications, which will decrease morbidity and mortality, ultimately improving patient outcomes. PMID- 22669003 TI - The importance of vital signs in the triage of injured patients. AB - BACKGROUND: Vital signs are indicators of a patient presenting to an emergency department (ED). Abnormal vital signs have been associated with an increased likelihood of admission to the hospital. Physicians have long recognized the importance of vital sign observations, and vital sign measurement has proven to be useful for detecting serious diseases during triage in EDs. METHODS: The study included all patients with injuries presented to the ED of a general hospital in Greece. For these patients, sex, age, cause of injury, vital signs at the time of admission to ED (systolic blood pressure, diastolic blood pressure, mean blood pressure, heart rate, and oxygen saturation), and the course of the patient (admission to hospital, discharge from ED) were recorded. The statistical analysis of data was done by the statistical package SPSS 15. It was performed using univariate regression and Spearman correlation coefficient. RESULTS: A total of 2703 patients were registered, of which 71% were men aged 31.9 +/- 0.38 years and 29% were women aged 45.7 +/- 0.79 years. The main causes of injury were car accident, motor accident, pedestrian accident, fall from a height, and assault. By logistic regression, the correlation was found between mean blood pressure, systolic blood pressure, oxygen saturation, and hospitalization or discharge of the patients. CONCLUSIONS: The measurement of mean blood pressure, systolic blood pressure, and oxygen saturation of the injured patients during the admission to the ED can predict the disease course of patients. PMID- 22669004 TI - Experiences and needs of families regarding prognostic communication in an intensive care unit: supporting families at the end of life. AB - This article reports the results of a study designed to explore the experiences and needs of family members for prognostic communication at end of life in an intensive care unit (ICU). Subjects in this qualitative study included 20 family members of patients at high risk for death in 1 adult medical/surgical ICU. All subjects were interviewed once utilizing a semistructured interview format, with approximately half interviewed multiple times during the ICU stay. Families described 5 themes of information-related "work": (1) hearing and recalling, (2) accessing, (3) interpreting, (4) retaining, and (5) utilizing information for decision making. Barriers, including accessing physicians and cognitive issues from high levels of stress, made this work difficult. Families described a need for prognostic information, especially if the prognosis was poor. Because hearing this news was difficult, they needed it communicated with respect, sensitivity, and compassion. Suggestions for clinical practice to support families in their information-related work are presented. Overall, the importance of providers approaching communication from a holistic perspective, extending beyond simply passing on information, is emphasized. Viewing communication as a therapeutic modality, and communicating with compassion, sensitivity, and a genuine sense of caring, can help provide both the information and the emotional support and comfort families desperately need. PMID- 22669005 TI - Agreement of corneal thickness measurement using slitlamp and ultrasound pachymetry. AB - PURPOSE: To estimate central corneal thickness (CCT) using a slitlamp biomicroscope and analyze its agreement with ultrasonic pachymetry. METHODS: Based on the clinical estimation of CCT on slitlamp examination, 133 eyes of 123 patients were assigned to 3 groups: CCT less than 500 MUm, 500 to 600 MUm, and greater than 600 MUm. An average of three readings was obtained for each patient using an ultrasound pachymeter. RESULTS: The primary diagnoses at the time of presentation were glaucoma (42, 31.5%), corneal opacity (20, 15%), keratoconus (14, 10.5%), corneal edema (14, 10.5%), and postkeratoplasty eyes (8, 6%). Thirty five (26.5%) eyes had no known ophthalmic diseases. There was an overall agreement of 86.5% in qualifying CCT into each of the 3 groups (kappa 0.76). The sensitivity and specificity of clinical estimation of CCT were found to be 96.26% (95% confidence interval [CI], 76.1%-94.2%) and 92.31% (95% CI, 78.7%-92.2%), respectively. The agreement was highest in patients with corneal edema (100%, kappa 1.00) and postkeratoplasty eyes (100%, kappa 1.00). The agreement was 82.9% (kappa 0.3) in normal eyes. CONCLUSIONS: Estimation of CCT by slitlamp examination is a reliable tool in clinical practice. In our study, there was a substantial agreement between clinically estimated CCT and ultrasonic pachymetry. This agreement was higher in eyes with abnormal corneal thickness compared with normal eyes. PMID- 22669006 TI - Candida fermentati: a rare yeast involved in fungal keratitis. AB - PURPOSE: The aim of this study was to report a rare case of fungal keratitis from Eastern India. METHODS: This is a case report. RESULTS: A 52-year-old man with a history of minor trauma presented with a total corneal ulcer and hypopyon in the left eye. Microbiologic examination of corneal scrapings showed yeast cells in direct smear and typical yeast colonies on multiple solid agar media. Identification of the organism isolated in the culture was performed using the D1/D2 region of the large subunit (LSU 28S rDNA)-based molecular technique. Polymerase chain reaction amplified a band with a sequence that was 100% homologous with that of Candida fermentati. The organism was susceptible to amphotericin B and anidulafungin and demonstrated resistance to voriconazole, itraconazole, and fluconazole. Therapeutic keratoplasty was performed, followed by the recurrence of the infection in the graft, which was controlled with topical and intracameral amphotericin B. At the end of 3 months, the affected eye had developed phthisis bulbi. CONCLUSIONS: This is the first report of isolation of C. fermentati, a species closely related to Candida guilliermondii, from keratitis. Molecular diagnostic techniques are helpful in the accurate identification of this organism, which is clinically important in view of an antifungal susceptibility pattern that differs from that of other yeasts and for selection of appropriate therapy. PMID- 22669007 TI - Antimicrobial efficacy tests of multipurpose contact lens care solutions simulating poor contact lens hygiene behaviors. AB - PURPOSE: The aim of this study was to simulate the biofilm formation in contact lens (CL) case under poor hygiene behaviors; antimicrobial efficacies of multipurpose solutions (MPSs) against biofilm on the lens case were evaluated. METHODS: Five MPSs (Epica Cold, Complete 10 min, ReNu MultiPlus, SoftOne Mois, and OPTI-FREE Plus) were tested. Lens cases containing ACUVUE2 were inoculated with 1*10, 10, or 10 colony-forming units (CFUs) of Staphylococcus epidermidis (SE). Each lens case was treated with 1 MPS for 4 hrs followed by the estimation of the number of SE by the CFU method. Disinfection efficacies of MPSs against SE biofilm were evaluated by biomicroscopy with safranin staining and scanning electron microscopy. RESULTS: Lens cases, inoculated with 1*10 CFU, were disinfected by all MPSs. Epica Cold, Complete 10 min, ReNu MultiPlus, and OPTI FREE showed almost a 2-log reduction of the CFU, whereas SoftOne Mois effect was almost a 1 log reduction, significantly lower than other MPSs (P<0.05). No biofilm formations were observed in Epica Cold, Complete 10 min, ReNu MultiPlus, and OPTI-FREE Plus-treated groups unlike significant biofilm formation in the SoftOne Mois-treated group (P<0.01). CONCLUSIONS: Greater efforts to educate patients regarding compliant lens care behavior are needed to reduce the incidence of CL-associated microbial keratitis. PMID- 22669009 TI - Conjunctival lymphangiectasia presenting as pediatric pseudopterygium. AB - OBJECTIVES: The aim of this study is to report a case of conjunctival lymphangiectasia simulating a pediatric pterygium. METHODS: A 10-year-old girl with Turner syndrome and familial history of pterygia presented because of a conjunctival growing lesion clinically consistent with pterygium in her left eye. Visual acuity (VA) was 20/20 in the right eye and 20/40 in the left eye. Cycloplegic refraction was +1.50sph -0.50cyl*93 degrees and +9.00sph 9.00cyl*180 degrees in the right and left eyes, respectively. RESULTS: Resection of the lesion with amniotic membrane implantation and conjunctival autograft was performed. The histologic examination revealed conjunctival lymphangiectasia. Ten months later, the patient did not show any signs of recurrence. Refraction in the left eye was +0.5sph -1.5cyl*70 degrees , and spontaneous VA was 20/20 in both eyes. CONCLUSIONS: Pediatric pseudopterygium may be the clinical presentation of several ocular surface disorders. Thus, pathologic analysis of this lesion should be considered to determine its exact nature. Surgery lessens the refractive defect and hastens visual recovery. PMID- 22669008 TI - The infant aphakia treatment study contact lens experience: one-year outcomes. AB - PURPOSE: We describe our experience correcting a cohort of infants with contact lenses in the Infant Aphakia Treatment Study. MATERIALS AND METHODS: Fifty-seven infants 1-6 months of age were randomized to contact lens wear. An examination under anesthesia was performed at the time of enrollment and at approximately 1 year of age. A traveling examiner assessed visual acuity at approximately 1 year of age. RESULTS: Forty-two treated eyes (74 %) were fitted with silicone elastomer (SE) contact lenses; 12 eyes (21 %) with rigid gas permeable (RGP) contact lenses, and 3 eyes (5%) wore both lens types. Median visual acuity was +0.80 logMAR in both lens type-wearing groups. The mean (+/- SD) keratometric power of the treated eyes was 46.3+/-2.8 D at baseline and 44.6+/-2.3 D at 1 year of age for a mean decrease of 0.2+/-0.2 D/mo. Keratometric astigmatism of treated eyes was 1.98+/-1.37 D at baseline and 1.62+/-0.98 D at 1 year of age for a mean decrease of 0.05+/-0.2 D/mo. The mean RGP lens base curve at baseline was 47.62 D+/-2.62 D versus 47.00 D+/-3.50 D at 12 months after surgery. Children wearing SE lenses required a mean of 10.9 replacements (range 2-24) compared to 16.8 replacements (range 8-32) for children wearing RGP lenses. Three adverse events occurred. CONCLUSIONS: Contact lenses were worn successfully with relatively few adverse events by a cohort of infants with unilateral aphakia. The visual acuity results were identical independent of the contact lens material or modality. RGP lenses needed replacement more often than SE lenses. PMID- 22669010 TI - Designing in the social context: using the social contextual model of health behavior change to develop a tobacco control intervention for teachers in India. AB - This article provides a theory-based, step-by-step approach to intervention development and illustrates its application in India to design an intervention to promote tobacco-use cessation among school personnel in Bihar. We employed a five step approach to develop the intervention using the Social Contextual Model of Health Behavior Change (SCM) in Bihar, which involved conducting formative research, classifying factors in the social environment as mediating mechanisms and modifying conditions, developing a creative brief, designing an intervention and refining the intervention based on pilot test results. The intervention engages users and non-users of tobacco, involves teachers in implementing and monitoring school tobacco control policies and maximizes teachers' role as change agents in schools and communities. Intervention components include health educator visits, discussions led by lead teachers, cessation assistance, posters and other educational materials and is implemented over the entire academic year. The intervention is being tested in Bihar government schools as part of a randomized-controlled trial. SCM was a useful framework for developing a tobacco control intervention that responded to teachers' lives in Bihar. PMID- 22669012 TI - Brain structural and functional connectivity and the progression of neuropathology in Alzheimer's disease. AB - In our contribution to this special issue focusing on advances in Alzheimer's disease (AD) research since the centennial, we will briefly review some of our own studies applying magnetic resonance imaging (MRI) measures of function and connectivity for characterization of genetic contributions to the neuropathology of AD and as candidate biomarkers. We review how functional MRI during both memory encoding and at rest is able to define APOE4 genotype-dependent physiological changes decades before potential development of AD and demonstrate changes distinct from those with healthy aging. More generally, imaging provides a powerful quantitative measure of phenotype for understanding associations arising from whole genome studies in AD. Structural connectivity measures derived from diffusion tensor MRI (DTI) methods offer additional markers of neuropathology arising from the secondary changes in axonal caliber and myelination that accompany decreased neuronal activity and neurodegeneration. We illustrate applications of DTI for more finely mapping neurodegenerative changes with AD in the thalamus in vivo and for defining neuropathological changes in the white matter itself. The latter efforts have highlighted how sensitivity to the neuropathology can be enhanced by using more specific DTI measures and interpreting them relative to knowledge of local white matter anatomy in the healthy brain. Together, our studies and related work are helping to establish the exciting potential of a new range of MRI methods as neuropathological measures and as biomarkers of disease progression. PMID- 22669011 TI - Maternal family history is associated with Alzheimer's disease biomarkers. AB - A family history of Alzheimer's disease (AD) increases one's risk of developing late-onset AD (LOAD), and a maternal family history of LOAD influences risk more than a paternal family history. Accumulating evidence suggests that a family history of dementia associates with AD-typical biomarker changes. We analyzed cross-sectional data from non-demented, mild cognitive impairment (MCI), and LOAD participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) with PET imaging using Pittsburgh Compound B (PiB, n = 99) and cerebrospinal fluid (CSF) analysis (n = 403) for amyloid-beta peptide (Abeta) and total tau. We assessed the relationship of CSF and PiB biomarkers and family history of dementia, as well as parent gender effects. In the larger analysis of CSF biomarkers, we assessed diagnosis groups individually. In the overall sample, CSF Abeta, tau/Abeta ratio, and global PiB uptake were significantly different between family history positive and negative groups, with markers of increased AD burden associated with a positive maternal family history of dementia. Moreover, a maternal family history of dementia was associated with significantly greater PiB Abeta load in the brain in the parietal cortex, precuneus, and sensorimotor cortex. Individuals with MCI positive for a maternal family history of dementia had significantly more markers of AD pathophysiology than individuals with no family history of dementia. A family history of dementia is associated with AD typical biomarker changes. These biomarker associations are most robust in individuals with a maternal family history, suggesting that a maternally inherited factor influences AD risk. PMID- 22669013 TI - Novel disease-modifying therapies for Alzheimer's disease. AB - Alzheimer's disease (AD) is the most common progressive dementia in the elderly and places an enormous burden on the individual and society. Presently, the treatments for AD are only symptomatic and do not halt the progression of the disease. With the recent advances in the understanding of the pathogenesis of AD in past years, numerous therapies which could modify the disease process are under active investigation. These therapies could attenuate or even reverse the neurodegenerative process by interfering with the underlying pathogenesis including amyloid-beta production, tau hyperphosphorylation, oxidative stress, inflammation, and excitotoxicity. In this review, new disease-modifying therapies which reduce amyloid-beta production, prevent tau hyperphosphorylation, and provide neuroprotective effects are described, including the results of in vitro and in vivo studies and clinical trials. Some typical therapies with disease modifying effects have also been discussed. PMID- 22669015 TI - Free-floating thrombus in right atrium. PMID- 22669016 TI - Abdominal cocoon in peritoneal dialysis--a fatal outcome. PMID- 22669017 TI - Congenital syphilis: remember to not forget. PMID- 22669014 TI - Patterns of compensation and vulnerability in normal subjects at risk of Alzheimer's disease. AB - Alzheimer's disease (AD) is the most frequent form of dementia in elderly individuals and its incidence and prevalence increases with age. This risk of AD is increased in the presence of genetic and demographic factors including apolipoprotein E 4 allele, lower education, and family history of AD. There are medical risk modifiers including systemic hypertension, diabetes mellitus, cardiovascular disease, and cerebrovascular disease that increase the vulnerability for AD. By contrast, there are lifestyle risk modifiers that reduce the effects of AD risk factors include diet and physical and cognitive activity. Our research has consistently shown that it is the interactions among these risk factors with the pathobiological cascade of AD that determine the likelihood of a clinical expression of AD-either as dementia or mild cognitive impairment. However, the association between "vulnerability" and "protective" factors varies with age, since the effects of these factors on the risk for AD may differ in younger (age < 80) versus older (age > 80) individuals. The understanding of the dynamic of these factors at different age periods will be essential for the implementation of primary prevention treatments for AD. PMID- 22669018 TI - Aortobronchial fistula successfully treated with thoracic endovascular aortic repair. PMID- 22669019 TI - Bilateral facial synkinesis in leprosy. AB - Leprosy is an important cause of cranial nerve palsy in endemic areas where it may be seen in upto 17.6% patients. The authors herein describe a rare case of bilaterally symmetrical facial synkinesis with video documentation and modified blink reflex. A 35-year-old gentleman presented with numbness involving right half of his face for 8 months and abnormal stretching sensations over both sides of his nose for one and a half months. Sensory and motor involvement of the right trigeminal nerve was detected along with bilaterally symmetrical facial synkinesis involving orbicularis oculi and nasalis. R(1) and R(2) responses consistent with mis-reinnervation were recorded on the left-side using orbicularis oculi and nasalis muscles. Skin biopsy revealed acid-fast bacilli and sural nerve biopsy, the presence of granulomas. After 3 months of follow-up on WHO multi-drug therapy, an improvement in facial sensations was observed but without any change in facial synkinetic movements. PMID- 22669020 TI - Autosomal recessive hypercholesterolaemia in a Morrocan family due to a mutation of the G266C LDL receptor. AB - Familial hypercholesterolaemia (FH) is quite common genetic disorder resulting in high low-density lipoprotein (LDL) cholesterol levels, but homozygous FH is rare. The authors describe a Moroccan family where a 24-year-old man and his 13-year old brother, born from a consanguineous union, showed characteristics of FH with large tendon, tuberous and planar xanthomas. They had already five deaths in the sibship before the age of 15 years. Blood analysis found high LDL cholesterol levels. Arterial assessment showed diffuse atherosis. Genetic study found that patients are homozygous for the mutation of G266C LDL receptor. Treatment with high doses of statins and ezetimibe was introduced reducing cholesterol up to 70%. Large xanthomas were removed surgically. The G266C mutation has been previously identified in Morocco. Early identification and adequate treatment of individuals with hypercholesterolaemia and their relatives are essential for prevention of early death in these populations. PMID- 22669021 TI - Subacute proximal leg weakness after a minor traffic accident in a patient treated with anticoagulants. AB - One day after a minor accident, an 85-year-old man developed headache and proximal left leg weakness. He was on warfarin due to atrial fibrillation. On hospital admission, a right posterior parasagittal subdural haematoma that was visualised on CT was considered as cause of all symptoms. Although no surgical intervention was performed he stayed for 2 weeks in a neurosurgical ward. Clinical deterioration occurred within the first days as he was not able to stand on his left leg or rise up from the sitting position. Headache had ceased, but the patient reported low abdominal pain. This condition remained stable for over 2 months although haematoma size decreased significantly. He was then examined for the first time by a neurologist who documented typical clinical features of femoral nerve palsy. Pelvic CT established the diagnosis of traumatic iliacus- and iliopsoas-muscle haematoma under anticoagulants as cause of subacute femoral mononeuropathy. PMID- 22669022 TI - A rare complication: lymphocele following a re-operative right thyroid lobectomy for multinodular goitre. AB - Lymphatic leakage is a rare complication of thyroid surgery, the risk of which increases in the presence of malignancy and correlates with the extent of surgery. Although primarily associated with left-sided thoracic duct injuries, lymphatic leaks may occur following right-sided neck dissections for metastatic thyroid cancer. However, the development of a lymphocele following a right-sided lobectomy for benign disease is exceptionally rare. The authors present the case of a patient who developed a cervical lymphocele 10 days after a re-operative right thyroid lobectomy for a multinodular goitre. The patient was successfully managed conservatively with a combination of dietary modification and high-dose octreotide. The reason for her presentation was most likely the result of an occult injury to a congenitally-aberrant lymphatic duct, brought into the operative field by postsurgical adhesions. The case serves to highlight the importance of subtle variations in lymphatic anatomy in the context of a re operative thyroidectomy. PMID- 22669023 TI - The absence of typical pneumonia symptoms in a patient with rheumatoid arthritis during tocilizumab and steroid treatment. AB - A 78-year-old woman with rheumatoid arthritis while being treated with tocilizumab and steroid treatment presented with pharyngeal pain and general malaise. She felt chills and vomited while waiting in the waiting room, in addition to urinary incontinence. An immediate evaluation of her condition indicated that she was in shock and a physical examination revealed moist rales in the right lung field. Her white cell count and C reactive protein level were within normal limits; however, a radiological study indicated pneumonia. Antibiotic treatment resulted in improvement of her condition. Blood culture later revealed bacteraemia due to Streptococcus pneumoniae. The anti-inflammatory effect of tocilizumab and steroid treatment may mask the typical symptoms and signs of infection, so physicians must be aware of the potential for hidden infection when such patients present with an unidentified complaint. PMID- 22669024 TI - A rare case of calcaneal tumour in a young adult. PMID- 22669025 TI - Cytomegalovirus retinitis with a CD4+T cell count of 147. PMID- 22669026 TI - Post-traumatic pseudoaneurysm of internal carotid artery: a cause of intractable epistaxis. AB - In this case report, the authors are presenting a case of a 35-year-old lady who presented to our clinic with recurrent episodes of massive epistaxis and loss of right eye vision for last 6 months following road traffic accident. There was no other significant medical and surgical history. Bleeding episodes were sometimes very severe with loss up to 400-500 cc and would stop spontaneously. She was given multiple blood transfusions after these episodes. A complete otorhinolaryngological examination including rigid endoscopy and coagulation investigation did not reveal any abnormality. CT with contrast of paranasal region showed blood within the right sphenoid sinus with linear fracture of the lateral wall with post-traumatic cavernous pseudoaneurysm of internal carotid artery localised to right sphenoid sinus. That was managed successfully by embolisation using a detachable balloon and a coil. She was followed up in the clinic at 6 weeks and 6 months interval with no symptoms. PMID- 22669027 TI - Hyponatraemia masking the diagnosis of cryptococcal meningitis. AB - Patients with acute hyponatraemia present with neurologic symptoms resulting from cerebral oedema induced by water movement into the brain. The author reports a male patient who presented to our emergency department with headache for 3 days and confusion for a day. The reported patient was on two immunosuppressive drugs, namely prednisone and azathiorprine for his ulcerative colitis. Laboratory data were consistent with syndrome of inappropriate antidiuretic hormone secretion (SIADH) which was appropriately corrected; however his mental status deteriorated. The patient's initial presentation was considered to be secondary to hyponatraemia. There was lapse of 36 h where the hyponatraemia was corrected; however the cause of the SIADH was not investigated. On further investigation of the patient a diagnosis of cryptococcal meningitis was ascertained. This case highlights the importance of considering a central nervous system infection in an immuno-suppressed patients presenting with hyponatraemia secondary to SIADH. PMID- 22669028 TI - Oesophageal perforation in extreme prematurity. AB - Management of oesophageal perforation in extremely premature babies is a challenge and carries a high morbidity. The authors report their experience of three separate cases of oesophageal perforation they encountered over the last 18 months in extremely premature neonates. In the first case, the diagnosis of oesophageal perforation was known in an otherwise stable baby who was treated conservatively with a good outcome. In the second and third cases, the patients proceeded to thoracotomy before the diagnosis of a perforated oesophagus was unveiled. A subsequent diagnosis of trisomy 18 and complex cardiac anomalies in the second case proved incompatible with life and treatment was withdrawn. In the final case, an oesophagostomy was fashioned with a gastrostomy for feeding postoperatively and gastric interposition is planned later this year. PMID- 22669029 TI - A fracture of the radial styloid associated with proximal avulsion of abductor pollicis longus and extensor pollicis brevis. AB - The authors present the case of a right hand dominant adult who sustained a fracture of the distal radial styloid with complete avulsion of the abductor pollicis longus and extensor pollicis brevis tendons at their musculotendinous junctions. The authors could not find any reports of these injuries occurring together in the literature. No formal tendon reconstructive procedure was performed but full functional use of the injured extremity has been regained. PMID- 22669030 TI - 'A harmless but confusing tumour on the anterior maxilla'. AB - Squamous odontogenic tumour (SOT) is a very rare benign neoplasm probably arising from rests of Malassez. Patients may present with an increase in the volume of the maxilla or mandible, tooth mobility, ulceration of the oral soft tissue, painful symptoms and tooth displacement. Radiographic features of SOT consist of a triangular-shaped radiolucent lesion adjacent to the roots of teeth. Histologically, care should be taken not to misdiagnose this condition as acanthomatous ameloblastoma or well-differentiated squamous cell carcinoma. The authors are presenting a case of a 65-year-old male patient who presented with a painless swelling and diagnosed to be having SOT. PMID- 22669031 TI - Chronic subdural haematoma management: an iatrogenic complication. Case report and literature review. AB - The authors report the case of a 45-year-old woman who presented to our institution with 10 days history of confusion and signs of progressive raised intracranial pressure as a result of a minor head injury occurred 4 weeks before. A brain CT-scan showed a large right hemispheric chronic subdural haematoma which was, as routinely, treated by burr-hole craniostomy and closed-drainage. Although the procedure was uneventful, the next day the patient developed a mild left hemiparesis associated to a slight global status worsening. A brain CT scan showed an intracerebral position of the drain with diffuse brain oedema and midline shift. Following drain removal the patient developed a serious neurological deterioration dropping the Glasgow coma scale to 8/15 as the result of an intracerebral and intraventricular haemorrhage along the removed drain trajectory. The clinical features of this iatrogenic complication are reported analysing also globally chronic subdural haematoma management and discussing pertinent literature. PMID- 22669032 TI - Transcriptomic signatures of attachment, NF-kappaB suppression and IFN stimulation in the catfish gill following columnaris bacterial infection. AB - Outbreaks of columnaris disease (Flavobacterium columnare) are common in wild and cultured freshwater fish worldwide. Disease occurrences, particularly those caused by virulent genomovar II isolates, in aquaculture species such as channel catfish can be devastating. In contrast to other important aquaculture pathogens, little is known about host immune responses to columnaris. Adhesion of F. columnare to gill tissue has been correlated in some previous studies to virulence and host susceptibility. Here, therefore, we conducted the first transcriptomic profiling of host responses to columnaris following an experimental challenge. We utilized Illumina-based RNA-seq expression profiling to examine transcript profiles at three timepoints (4h, 24h, and 48h) in catfish gill after bath immersion infection. Enrichment and pathway analyses of the differentially expressed genes revealed several central signatures following infection. These included the dramatic upregulation of a rhamnose-binding lectin, with putative roles in bacterial attachment and aggregation, suppression of NF kappaB signalling via IkappaBs, BCL-3, TAX1BP1, and olfactomedin 4, and strong induction of IFN-inducible responses including iNOS2b, IFI44, and VHSV genes. Fifteen differentially expressed genes with varying expression profiles by RNA seq, were validated by QPCR (correlation coefficients 0.85-0.94, p-value <0.001). Our results highlight several putative immune pathways and individual candidate genes deserving of further investigation in the context of development of therapeutic regimens and laying the foundation for selection of resistant catfish lines against columnaris. PMID- 22669033 TI - Considerations for imaging the adolescent brain. AB - In recent years the number of functional neuroimaging studies on adolescence has exploded. These studies have led to important new insights about the relation between functional brain development and behavior. However, special consideration is warranted when working with adolescents. In this review, we review variables, including pubertal stage, sleep patterns and pregnancy, which are particularly relevant for developmental cognitive neuroscience studies involving adolescents. Consideration of the unique challenges associated with adolescence will help the growing field of developmental neuroimaging standardize procedures and will eventually facilitate interpretation across studies. PMID- 22669034 TI - Flexible rule use: common neural substrates in children and adults. AB - Flexible rule-guided behavior develops gradually, and requires the ability to remember the rules, switch between them as needed, and implement them in the face of competing information. Our goals for this study were twofold: first, to assess whether these components of rule-guided behavior are separable at the neural level, and second, to identify age-related differences in one or more component that could support the emergence of increasingly accurate and flexible rule use over development. We collected event-related fMRI data while 36 children aged 8 13 and adults aged 20-27 performed a task that manipulated rule representation, rule switching, and stimulus incongruency. Several regions - left dorsolateral prefrontal cortex (DLPFC), left posterior parietal cortex, and pre-supplementary motor area - were engaged by both the rule representation and the rule-switching manipulations. These regions were engaged similarly across age groups, though contrasting timecourses of activation in left DLPFC suggest that children updated task rules more slowly than did adults. These findings support the idea that common networks can contribute to a variety of executive functions, and that some developmental changes take the form of changes in temporal dynamics rather than qualitative changes in the network of brain regions engaged. PMID- 22669035 TI - Withholding response in the face of a smile: age-related differences in prefrontal sensitivity to Nogo cues following happy and angry faces. AB - The modulation of control processes by stimulus salience, as well as associated neural activation, changes over development. We investigated age-related differences in the influence of facial emotion on brain activation when an action had to be withheld, focusing on a developmental period characterized by rapid social-emotional and cognitive change. Groups of kindergarten and young school aged children and a group of young adults performed a modified Go/Nogo task. Response cues were preceded by happy or angry faces. After controlling for task performance, left orbitofrontal regions discriminated trials with happy vs. angry faces in children but not in adults when a response was withheld, and this effect decreased parametrically with age group. Age-related changes in prefrontal responsiveness to facial expression were not observed when an action was required, nor did this region show age-related activation changes with the demand to withhold a response in general. Such results reveal age-related differences in prefrontal activation that are specific to stimulus valence and depend on the action required. PMID- 22669037 TI - A 4.5 Mb terminal deletion of chromosome 12p helps further define a psychosis associated locus. AB - A 12 year-old girl presented with cognitive disability and dysmorphic features. Chromosome microarray analysis revealed a de novo, approximately 4.5 Mb terminal deletion of the short arm of chromosome 12 at 12p13.33 region: chr12:100712 4607067. At 13 years this patient developed psychotic manifestations and was admitted to a psychiatric department for treatment. She started hearing voices, talking to herself and laughing without reason. We have previously reported a male individual with psychotic manifestations and a larger (6.2 Mb) terminal deletion in the same chromosomal region. The present case along with previous reports, define a 2 Mb region on chromosome 12p, where a psychosis-associated gene may be located. Included in this psychosis-associated area are 18 OMIM listed genes. PMID- 22669036 TI - Altered error-related brain activity in youth with major depression. AB - Depression is associated with impairments in cognitive control including action monitoring processes, which involve the detection and processing of erroneous responses in order to adjust behavior. Although numerous studies have reported altered error-related brain activity in depressed adults, relatively little is known about age-related changes in error-related brain activity in depressed youth. This study focuses on the error-related negativity (ERN), a negative deflection in the event-related potential (ERP) that is maximal approximately 50ms following errors. High-density ERPs were examined following responses on a flanker task in 24 youth diagnosed with MDD and 14 low-risk healthy controls (HC). Results indicate that compared to HC, MDD youth had significantly smaller ERN amplitudes and did not exhibit the normative increases in ERN amplitudes as a function of age. Also, ERN amplitudes were similar in depressed youth with and without comorbid anxiety. These results suggest that depressed youth exhibit different age-related changes in brain activity associated with action monitoring processes. Findings are discussed in terms of existing work on the neural correlates of action monitoring and depression and the need for longitudinal research studies investigating the development of neural systems underlying action monitoring in youth diagnosed with and at risk for depression. PMID- 22669038 TI - Electroconvulsive therapy in a patient after radiation treatment of a brain metastasis: a case report. AB - Major depression has a high incidence in patients with cancer, but treatment guidelines for this vulnerable population are missing and antidepressants seem to be less effective than in patients not affected by cancer. We report the case of a patient with bronchial cancer with a single temporo-occipital brain metastasis that had been treated by radiotherapy (whole-brain radiation, 40 Gy, followed by a stereotactic radiotherapy, 15 Gy). The patient developed a major depressive episode and was successfully treated with electroconvulsive therapy without relevant adverse events. This case further underscores the safety and effectiveness of electroconvulsive therapy after radiotherapy of the brain and demonstrates a viable alternative for severely depressed patients with cancer who do not adequately respond to psychotherapy or pharmacotherapy alone. PMID- 22669039 TI - Strong inhibition of celastrol towards UDP-glucuronosyl transferase (UGT) 1A6 and 2B7 indicating potential risk of UGT-based herb-drug interaction. AB - Celastrol, a quinone methide triterpene isolated from Tripterygium wilfordii Hook F., has various biochemical and pharmacological activities, and is now being developed as a promising anti-tumor agent. Inhibitory activity of compounds towards UDP-glucuronosyltransferase (UGT) is an important cause of clinical drug drug interactions and herb-drug interactions. The aim of the present study is to investigate the inhibition of celastrol towards two important UDP glucuronosyltransferase (UGT) isoforms UGT1A6 and UGT2B7. Recombinant UGT isoforms and non-specific substrate 4-methylumbelliferone (4-MU) were used. The results showed that celastrol strongly inhibited the UGT1A6 and 2B7-mediated 4-MU glucuronidation reaction, with 0.9 +/- 0.1% and 1.8 +/- 0.2% residual 4-MU glucuronidation activity at 100 MUM of celastrol, respectively. Furthermore, inhibition kinetic study (Dixon plot and Lineweaver-Burk plot) demonstrated that celastrol noncompetitively inhibited the UGT1A1-mediated 4-MU glucuronidation, and competitively inhibited UGT2B7-catalyzed 4-MU glucuronidation. The inhibition kinetic parameters (Ki) were calculated to be 0.49 MUM and 0.045 MUM for UGT1A6 and UGT2B7, respectively. At the therapeutic concentration of celastrol for anti tumor utilization, the possibility of celastrol-drug interaction and celastrol containing herbs-drug interaction were strongly indicated. However, given the complicated nature of herbs, these results should be viewed with more caution. PMID- 22669040 TI - Water assisted growth of C60 rods and tubes by liquid-liquid interfacial precipitation method. AB - C60 nanorods with hexagonal cross sections are grown using a static liquid-liquid interfacial precipitation method in a system of C60/m-dichlorobenzene solution and ethanol. Adding water to the ethanol phase leads instead to C60 tubes where both length and diameter of the C60 tubes can be controlled by the water content in the ethanol. Based on our observations we find that the diameter of the rods/tubes strongly depends on the nucleation step. We propose a liquid-liquid interface growth model of C60 rods and tubes based on the diffusion rate of the good C60 containing solvent into the poor solvent as well as on the size of the crystal seeds formed at the interface between the two solvents. The grown rods and tubes exhibit a hexagonal solvate crystal structure with m-dichlorobenzene solvent molecules incorporated into the crystal structure, independent of the water content. An annealing step at 200 degrees C at a pressure < 1 kPa transforms the grown structures into a solvent-free face centered cubic structure. Both the hexagonal and the face centered cubic structures are very stable and neither morphology nor structure shows any signs of degradation after three months of storage. PMID- 22669041 TI - Pristimerin, a triterpenoid, inhibits tumor angiogenesis by targeting VEGFR2 activation. AB - Pristimerin is a triterpenoid isolated from Celastrus and Maytenus spp. that has been shown to possess a variety of biological activities, including anti-cancer activity. However, little is known about pristimerin's effects on tumor angiogenesis. In this study, we examined the function and the mechanism of this compound in tumor angiogenesis using multiple angiogenesis assays. We found that pristimerin significantly reduced both the volume and weight of solid tumors and decreased angiogenesis in a xenograft mouse tumor model in vivo. Pristimerin significantly inhibited the neovascularization of chicken chorioallantoic membrane (CAM) in vivo and abrogated vascular endothelial growth factor (VEGF) induced microvessel sprouting in an ex vivo rat aortic ring assay. Furthermore, pristimerin inhibited the VEGF-induced proliferation, migration and capillary like structure formation of human umbilical vascular endothelial cells (HUVECs) in a concentration-dependent manner. Mechanistic studies revealed that pristimerin suppressed the VEGF-induced phosphorylation of VEGF receptor 2 kinase (KDR/Flk-1) and the activity of AKT, ERK1/2, mTOR, and ribosomal protein S6 kinase. Taken together, our results provide evidence for the first time that pristimerin potently suppresses angiogenesis by targeting VEGFR2 activation. These results provide a novel mechanism of action for pristimerin which may be important in the treatment of cancer. PMID- 22669042 TI - Functional and preliminary characterisation of hydrocolloid from tamarillo (Solanum betaceum Cav.) puree. AB - Hydrocolloid from tamarillo (Solanum betaceum Cav.) puree was extracted using water and characterised for the first time. Proximate compositions of the extracted hydrocolloid were also determined. Functional characteristics such as water-holding capacity, oil-holding capacity, emulsifying activity, emulsion stability, foaming capacity and stability of the hydrocolloid were evaluated in comparison to that of commercial hydrocolloids. Its functional groups and degree of esterification were determined using Fourier Transform Infrared (FT-IR) spectroscopy. Monosaccharide profiling was done using reverse-phase high pressure liquid chromatography (RP-HPLC). Screening of various fruits for high hydrocolloid yield after water extraction resulted in tamarillo giving the highest yield. The yield on dry weight basis was 8.30%. The hydrocolloid constituted of 0.83% starch, 21.18% protein and 66.48% dietary fibre with 49.47% degree of esterification and the monosaccharides identified were mannose, ribose, rhamnose, galacturonic acid, glucose, galactose, xylose and arabinose. Higher oil holding capacity, emulsifying activity and emulsion stability compared to commercial hydrocolloids propose its possible application as a food emulsifier and bile acid binder. Foaming capacity of 32.19% and good foam stabilisation (79.36% of initial foam volume after 2 h of foam formation) suggest its promising application in frothy beverages and other foam based food products. These findings suggest that water-extracted tamarillo hydrocolloid can be utilised as an alternative to low methoxyl pectin. PMID- 22669043 TI - Dot immunobinding assay method with chlorophyll removal for the detection of southern rice black-streaked dwarf virus. AB - Southern rice black-streaked dwarf virus (SRBSDV), a new virus from Fiji, has seriously damaged rice crops in southern China and northern Vietnam in recent years. This virus is difficult to diagnose in the early stages of infection, and is very destructive at the late stage. In the present study, a dot immunobinding assay (DIBA) that has a high sensitivity for diagnosing SRBSDV was developed. Two kinds of treatment for the DIBA were evaluated to determine the most effective one for removing chlorophyll interferences via rice extraction. The first included several reagents to remove chlorophyll, namely, the alkaline reagents like magnesium oxide and alumina oxide, the adsorbent reagents like activated carbon and bentonite, as well as the extraction agent acetone. The second and third treatments, which were used to remove chlorophyll in blot membrane nitrocellulose and polyvinylidene fluoride (PVDF), included several organic solvents containing methanol, ethanol, acetone, ethyl acetate, and diethyl ether. The results showed that activated carbon and methanol yielded the best contrasting purple color for the infected samples by decreasing the chlorophyll content. PMID- 22669044 TI - Arginine-rich cell-penetrating peptides deliver gene into living human cells. AB - Transgenesis is a process that introduces exogenous nucleic acids into the genome of an organism to produce desired traits or evaluate function. Improvements of transgenic technologies are always important pursuit in the last decades. Recently, cell-penetrating peptides (CPPs) were studied as shuttles that can internalize into cells directly and serve as carriers to deliver different cargoes into cells. In the present study, we evaluate whether arginine-rich CPPs can be used for gene delivery into human cells in a noncovalent fashion. We demonstrate that three arginine-rich CPPs (SR9, HR9, and PR9) are able to transport plasmid DNA into human A549 cells. For the functional gene assay, the CPP-delivered plasmid DNA containing the enhanced green fluorescent protein (EGFP) coding sequence could be actively expressed in cells. The treatment of calcium chloride did not facilitate the CPP-mediated transfection efficiency, but enhance the gene expression intensity. Mechanistic studies further revealed that HR9/DNA complexes mediate the direct membrane translocation pathway for gene delivery. Our results suggest that arginine-rich CPPs, especially HR9, appear to be a high efficient and promising tool for gene transfer. PMID- 22669045 TI - Copy number variations of 11 macronuclear chromosomes and their gene expression in Oxytricha trifallax. AB - Ciliated protozoa are peculiar for their nuclear dimorphism, wherein two types of nuclei divide nuclear functions: a germline micronucleus (MIC) is transcriptionally inert during vegetative growth, but serves as the genetic blueprint for the somatic macronucleus (MAC), which is responsible for all transcripts supporting cell growth and reproduction. While all the advantages/disadvantages associated with nuclear dimorphism are not clear, an essential advantage seems to be the ability to produce a highly polyploid MAC, which then allows for the maintenance of extremely large single cells - many ciliate cells are larger than small metazoa. In some ciliate classes, chromosomes in the MAC are extensively fragmented to create extremely short chromosomes that often carry single genes, and these chromosomes may be present in different copy numbers, resulting in different ploidies. While using gene copy number to regulate gene expression is limited in most eukaryotic systems, the extensive fragmentation in some ciliate classes provides this opportunity to every MAC gene. However, it is still unclear if this mechanism is in fact used extensively in these ciliates. To address this, we have quantified copy numbers of 11 MAC chromosomes and their gene expression in Oxytricha trifallax (CI: Spirotrichea). We compared copy numbers between two subpopulations of O. trifallax, and copy numbers of 7 orthologous genes between O. trifallax and the closely related Stylonychia lemnae. We show that copy numbers of MAC chromosomes are variable, dynamic, and positively correlated to gene expression. These features might be conserved in all spirotrichs, and might exist in other classes of ciliates with heavily fragmented MAC chromosomes. PMID- 22669046 TI - Small inverted repeats drive mitochondrial genome evolution in Lake Baikal sponges. AB - Demosponges, the largest and most diverse class in the phylum Porifera, possess mitochondrial DNA (mtDNA) markedly different from that in other animals. Although several studies investigated evolution of demosponge mtDNA among major lineages of the group, the changes within these groups remain largely unexplored. Recently we determined mitochondrial genomic sequence of the Lake Baikal sponge Lubomirskia baicalensis and described proliferation of small inverted repeats (hairpins) that occurred in it since the divergence between L. baicalensis and the most closely related cosmopolitan freshwater sponge Ephydatia muelleri. Here we report mitochondrial genomes of three additional species of Lake Baikal sponges: Swartschewskia papyracea, Rezinkovia echinata and Baikalospongia intermedia morpha profundalis (Demospongiae, Haplosclerida, Lubomirskiidae) and from a more distantly related freshwater sponge Corvomeyenia sp. (Demospongiae, Haplosclerida, Metaniidae). We use these additional sequences to explore mtDNA evolution in Baikalian sponges, paying particular attention to the variation in the rates of nucleotide substitutions and the distribution of hairpins, abundant in these genomes. We show that most of the changes in Lubomirskiidae mitochondrial genomes are due to insertion/deletion/duplication of these elements rather than single nucleotide substitutions. Thus inverted repeats can act as an important force in evolution of mitochondrial genome architecture and be a valuable marker for population- and species-level studies in this group. In addition, we infer (((Rezinkovia+Lubomirskia)+Swartschewskia)+Baikalospongia) phylogeny for the family Lubomirskiidae based on the analysis of mitochondrial coding sequences from freshwater sponges. PMID- 22669048 TI - Current world literature. PMID- 22669047 TI - Environmental exposures, epigenetics and cardiovascular disease. AB - PURPOSE OF REVIEW: Epigenetic modifications are heritable alterations of the genome, which can govern gene expression without altering the DNA sequence. The purpose of this review is to render an overview of the possible mechanisms of epigenetic regulation of gene expression in response to environmental pollutants leading to cardiovascular diseases (CVD). RECENT FINDINGS: An era of cataloging epigenetic marks of the various diseased states has recently commenced, including those within the genes responsible for atherosclerosis, ischemia, hypertension and heart failure. From varied study approaches directed either toward the general understanding of the key pathway regulatory genes, or sampling population cohorts for global and gene-specific changes, it has been possible to identify several epigenetic signatures of environmental exposure relevant to CVD. Signatures of epigenetic dysregulation can be detected in peripheral blood samples, even within a few hours of environmental exposure. However, the field now faces the demand for thorough, systematic, rationalized approaches to establish the relation of exposure-driven epigenetic changes to clinical outcomes, by using sophisticated and reliable research designs and tools. SUMMARY: An understanding of chromatin remodelling in response to environmental stimuli conducive to CVD is emerging, with the promise of novel diagnostic and therapeutic candidates. PMID- 22669050 TI - Patient-centered innovation in health care organizations: a conceptual framework and case study application. AB - BACKGROUND: Patient-centered innovation is spreading at the federal and state levels. A conceptual framework can help frame real-world examples and extract systematic learning from an array of innovative applications currently underway. The statutory, economic, and political environment in Washington State offers a special contextual laboratory for observing the interplay of these factors. PURPOSE: We propose a framework for understanding the process of initiating patient-centered innovations-particularly innovations addressing patient-centered goals of improved access, continuity, communication and coordination, cultural competency, and family- and person-focused care over time. The framework to a case study of a provider organization in Washington State actively engaged in such innovations was applied in this article. METHODS: We conducted a selective review of peer-reviewed evidence and theory regarding determinants of organizational change. On the basis of the literature review and the particular examples of patient-centric innovation, we developed a conceptual framework. Semistructured key informant interviews were conducted to illustrate the framework with concrete examples of patient-centered innovation. FINDINGS: The primary determinants of initiating patient-centered innovation are (a) effective leadership, with the necessary technical and professional expertise and creative skills; (b) strong internal and external motivation to change; (c) clear and internally consistent organizational mission; (d) aligned organizational strategy; (e) robust organizational capability; and (f) continuous feedback and organizational learning. The internal hierarchy of actors is important in shaping patient-centered innovation. External financial incentives and government regulations also significantly shape innovation. PRACTICE IMPLICATIONS: Patient centered care innovation is a complex process. A general framework that could help managers and executives organize their thoughts around innovation within their organization is presented. PMID- 22669051 TI - Radioiodine therapy in Graves' disease: is it possible to predict outcome before therapy? AB - OBJECTIVE: To assess the predictability of outcome and evaluate the factors that may lead to treatment failure in patients with Graves' disease who are treated with a single dose of radioiodine. MATERIALS AND METHODS: This is a retrospective study of 123 patients (M: 42; F: 81) with Graves' disease who received radioiodine therapy with a single fixed (10 mCi) dose for hyperthyroidism. Pretreatment age, sex, BMI, type of anti-thyroid drug used, propylthiouracil doses, iodine uptake, uptake ratio (4/24 h radioiodine uptake), and thyroid volume of the patients in whom radioiodine therapy succeeded or failed were compared. RESULTS: Post-therapy follow-up revealed that therapy failed in 22% of the patients. Iodine uptakes and uptake ratios and volumes were found to be significantly higher in patients in whom therapy failed. It was observed that uptake ratio was at least 1 in 25 patients (20%), and therapy failed in 20 (80%) of these patients. Of the 98 patients (80%) in whom uptake ratio was less than 1, therapy was unsuccessful in only seven (7%). CONCLUSION: Uptake ratio is a simple index that may be used to predict the patients in whom therapy may fail or succeed. In patients with Graves' disease who have an uptake ratio of less than 1, radioiodine appears to be an effective dose with high success rates. In contrast, because of the high rates of failure in patients with an uptake ratio of at least 1, use of radioiodine therapy at a dose of 10 mCi does not seem to be appropriate. PMID- 22669052 TI - 18F-FDG PET-CT in the evaluation of paraneoplastic syndromes: experience at a regional oncology centre. AB - OBJECTIVES: Paraneoplastic syndromes (PNS) are remote manifestations of malignancy unrelated to tumour invasion or metastases. They pose a diagnostic challenge because of diverse presentations. (18)F-Fluorodeoxyglucose ((18)F-FDG) PET-CT is an emerging technique for the detection of malignancy; however, there is a paucity of data with regard to its role in the evaluation of PNS and its relation to pretest clinical risk. METHODS: A retrospective review of the database at the West of Scotland PET centre from 2007 to 2010 was conducted. Data extracted included demographics, clinical and pathological diagnosis, presence of classical syndromes, cross-sectional imaging, PET-CT imaging and management changes. A clinical scoring system was constructed to evaluate the pretest likelihood of having PNS, and the impact of a subsequent positive PET-CT scan was evaluated. RESULTS: A total of 68 consecutive patients with a median age (range) of 58 (23-82) years, of whom 44 (65%) were female, were included. Symptoms were neurological in 55 (81%), musculoskeletal in five (7%), endocrine in three (4%) and constitutional in five (7%) patients. Forty-three (62%) patients had a classical paraneoplastic syndrome and 34 (50%) had positive biomarkers. Eighteen (26%) patients had a positive PET-CT result. PET-CT was concordant with the clinical scoring in 49 (72%) patients; it upgraded the score in eight (12%) patients, and downgraded the score in 11 (16%) patients. Eight (12%) patients had confirmed malignancy. PET-CT was estimated to have 100% sensitivity, 82% specificity, 42% positive predictive value and 100% negative predictive value. CONCLUSION: PET-CT is a highly sensitive and specific imaging technique in the evaluation of PNS and adds confidence to clinical likelihood. PMID- 22669053 TI - Role of SPECT/CT in differentiated thyroid cancer. AB - Radioiodine scintigraphy and therapy has played a major role in the treatment and follow-up of thyroid cancer patients for decades. Single-photon emission computed tomography/computed tomography in this setting is emerging as a useful tool in accurately localizing sites of pathological uptake and physiological mimics of disease, thus providing more accurate staging prognostic information for risk stratification, which in turn tailors management and follow-up regimes. This review presents the current evidence and potential indications of single-photon emission computed tomography/computed tomography in thyroid cancer. PMID- 22669054 TI - The piezoelectric osteotomy technique compared to the one with rotary instruments in the surgery of included third molars. A clinical study. AB - AIM: The purpose of this study is to compare surgical times, the saving of bonytissues, the postoperative course of the extraction of included third molars in patients treated with piezoelectric surgery compared to those treated with conventional rotary instruments. METHODS: The study included 140 patients with upper and lower third molars included. 70 of them were treated with osteotomy using conventional rotary instruments (Group 1) and 70 more with osteotomy through piezosurgery Mectron(r) (GROUP 2). The treatment protocol was the same for both groups. The time of surgery and the saving of bonytissues in the intra operative have been estimated; moreover, 24-48-72 hours and 7 days after the surgery, two other parameters have been estimated: facial swelling and trismus. The swelling, trismus and the saving of bony tissues were assessed by a surgery gauge. RESULTS: The average surgical time was 15 minutes in Group 1 and 20 minutes in Group 2. The savings of bonytissues was greater in Group 2 than in group 1 by 2.7 mm. The average facial swelling was 6.23 mm for group 1 and 2.86 mm for group 2 24 hours after the surgery, of 5.22 mm for group 1 and 1.76 mm for group 2 48 hours after the intervention, of 3.75 mm for Group 1 and 0.85 for group 2 72 hours after the surgery, of 0.86 mm for group 1 and 0.12 for group 2. The average trismus was of 14.76 mm in Group 1 and 11.15 mm in Group 2. Statistical analysis showed a significant reduction of swelling, trismus and a bigger saving of bony tissues in Group 2 and a reduction in surgical time in Group 1. CONCLUSION: The osteotomy technique with a piezoelectric instrument has produced a significant reduction in facial swelling, trismus and a bigger saving of bony tissues than with conventional rotary instruments. A slight lengthening in terms of surgical time has been recorded, compared to the use of conventional rotary instruments. PMID- 22669055 TI - Influence of the volume of composite and photoactivation method on push-out bond strength and Knoop hardness of a resin composite. AB - AIM: The aim of this paper was to evaluate the influence of modulated photoactivation methods and volume of composite on Knoop hardness (KHN) and push out bond strength (PBS) of Filtek Z350 to root dentin. METHODS: Three volumes (small, medium and large) of composite were bulk inserted in cavities prepared in 90 premolars. The specimens were photoactivated with continuous light, pulse delay, or soft-start methods and submitted to PBS and KHN tests. The failure pattern was evaluated in stereomicroscope after the bond strength test. The data were submitted to two-way ANOVA and Tukey's test (P<0.05). RESULTS: Modulated photoactivation methods showed a higher PBS than continuous method (P<0.05). Medium volume of composite showed higher PBS than small and large volumes when photoactivated with continuous method (P<0.05). Pulse-delay significantly increased KHN for medium and large volumes in comparison to continuous method (P<0.05). Medium volume of composite showed KHN significantly higher than small and large volumes (P<0.05). CONCLUSION: The volume of composite influenced the PBS and KHN of resin composites. Pulse-delay showed the highest bond strength to dentin, as well KHN similar to the conventional method. The analysis of the failure pattern showed predominance of adhesive failure. PMID- 22669056 TI - Photo-elastic investigation of influence of dental implant shape and prosthetic materials to patterns of stress distribution. AB - AIM: Occlusal loading has to be considered a key factor influencing bone resorption due to the stress transmitted to surrounding tissues by the implant abutment structure. The aim of this study was to evaluate, through a photo elastic investigation, the patterns of tensions distribution of two different implant shapes, which were cylindrical and conical. METHODS: A 100N load was applied to two implant-abutment structures (with and without a metal-ceramic crown) incorporated in photo-elastic resin. Modification in light refraction were recorded and analyzed through a computerized software. Measurements of stripe extension and position were evaluated. RESULTS: Stress distribution around tapered implant was evaluated to be more uniform than in cylindrical one which demonstrated a high stress concentration at the more cervical region and in the apical region. The presence of a metal-ceramic crown caused an increase in tensions at the implant-resin interface. CONCLUSION: Conical implants distributed stresses to a larger and well-defined volume of resin and this can cause a decrease of forces acting at the interface. This could be due to the "wedge effect" of this fixture shape which could be considered superior in terms of stress distribution than cylindrical one. PMID- 22669057 TI - Effect of polymerization cycles on the linear dimensional change, hardness and impact strength of denture base acrylic resins. AB - AIM: This study verified the effect of polymerizing cycles on the linear dimensional change, hardness and impact strength of denture acrylic resins. METHODS: One hundred and twenty samples (N.=10) each for the Classico and Vipi acrylic resins were made according to the manufacturers' instructions. The polymerization cycles were: 1- water bath at 74 oC for 9 hr; 2- water bath at 74oC for 8 hr and temperature increased to 100 oC for 1 hr; 3- water bath at 74 oC for 2 hr and temperature increased to 100 oC for 1 hr; and 4- water bath at 120oC and 60 pounds pressure for 1 hr. Samples were deflasked after flask cooling and submitted to finishing. Linear distances between referential points in the samples were measured at deflasking and after water storage for 7 and 30 days with a comparator microscope with an accuracy of 0.0005 mm. Knoop hardness test was accomplished in a durometer with a load of 25 gf for 10 sec and an average of three indentations was considered for the sample hardness. Impact strength (kgf/cm2) was measured by the Charpy system with load of 40 kpcm. Data were submitted to ANOVA and Tukey's test (5%). RESULTS: Dimensional changes in the A-B and A-C distances, hardness values and impact strength for Classico and Vipi resins were differently influenced by the polymerization cycles, when deflasking and water storage for 7 and 30 days were considered. CONCLUSION: Linear dimensional change, hardness and impact strength of denture acrylic resins were differently affected by the polymerization cycles. PMID- 22669058 TI - Assessment of surface hardness of acrylic resins submitted to accelerated artificial aging. AB - AIM: The aim of this study was to assess the influence of accelerated artificial aging (AAA) on the surface hardness of acrylic resins. METHODS: The following three commercial brands of acrylic resins were tested: Vipi Flash (autopolymerized resin), Vipi Wave (microwave heat-polymerized resin) and Vipi Cril (conventional heat-polymerized resin). To perform the tests, 21 test specimens (65x10x3 mm) were made, 7 for each resin. Three surface hardness readings were performed for each test specimen, before and after AAA, and the means were submitted to the following tests: Kolmogorov-Smirnov (P>0.05), Levene Statistic, Two-way ANOVA, Tukey Post Hoc (P<0.05) with the SPSS Statistical Software 17.0. RESULTS: The analysis of the factors showed significant differences in the hardness values (P<0.05). Before aging, the autopolymerized acrylic resin Vipi Flash showed lower hardness values when compared with the heat polymerized resin Vipi Cril (P=0.001). After aging, the 3 materials showed similar performance when compared among them. The Vipi Cril was the only one affected by AAA and showed lower hardness values after this procedure (Pp=0.003). CONCLUSION: It may be concluded that accelerated artificial aging influenced surface hardness of heat-polymerized acrylic resin Vipi Cril. PMID- 22669059 TI - Oral koilocytic dysplasia: long-term clinical control. A case report. AB - Leukoplakia, a common lesion in the oral cavity, is considered a premalignant lesion that can develop into carcinoma. In 1986, a group of pathologists described a variant of epithelial dysplasia and named it "koilocytic dysplasia" (KD). This article presents a case of KD that was identified for 12 years as "carcinoma in situ". Even after removal of the lesion, it recurred with no signs of malignancy. The histopathological findings revealed all of the signs of KD (koilocytosis, acanthosis, multinucleated keratinocytes and atypical mitoses). Liquid-based cytology and hybrid capture were performed to confirm the diagnosis. Despite a professional recommendation to have the lesion removed surgically, the patient chose periodic clinical control. The mechanism of HPV transmission in the oral cavity still remains partially unknown. Additional studies on this subject are required to better understand the role of HPV in cell transformation in the oral cavity. PMID- 22669060 TI - Oral manifestation upon short time cocaine abuse. A case report. AB - Effects of cocaine abuse on the oral mucosa are still poorly defined. Herein, a case of an 18-year-old male patient with a 15-day history of persistent painful ulcers and aphthous lesions of unknown etiology and with no other remarkable manifestations, is presented. All of the laboratory tests performed showed to be within normal ranges. Only subsequently, the patient admitted a cocaine abuse, through smoking and rubbing, over the last 15 days. Finally, after 15 days of interruption of cocaine abuse the oral lesions showed complete regression. PMID- 22669061 TI - Unusual anchor pins placement and protocol deviations during computer-based implant placement in a patient with severe mandibular bone atrophy. A case report. AB - The aim of the study was to describe an unusual method to stabilize the surgical template during the treatment of a severely resorbed edentulous mandible by means of computer-guided implant surgery. Pre-operative computer-based planning revealed the difficulty to stabilize the surgical template in a 67-year-old healthy woman. A deviation of the original NobelGuideTM protocol was performed to ensure the stability of the surgical template: four anchor pins were used to stabilize the surgical template, two in the buccal side of the anterior template and two unusual pins were placed in the lingual site. Four straight TiUnite(r) Nobel BiocareTM implants were then placed, according to a modified All-on-4TM concept procedure, to avoid graft procedures and to reduce the cumulative chair side treatment time and costs. A temporary restoration was placed immediately after implant placement. Three months later a definitive, full acrylic restoration was delivered. PMID- 22669062 TI - Development of an ultra-sensitive enzyme immunoassay for human insulin autoantibodies. AB - OBJECTIVES: We developed an ultrasensitive enzyme immunoassay (ICT-EIA) for insulin autoantibody (IAA) measurements to better understand the pathophysiology of diabetes. DESIGN AND METHODS: We developed ICT-EIA for IAA and measured IAA in 24 patients with type 1 diabetes, 30 patients with type 2 diabetes, 30 patients with methimazole-treated Graves' disease, 20 patients with Hashimoto's disease, 9 patients with hyperinsulinemia, and 73 healthy control subjects. RESULTS: The conventional ELISA identified 3 patients with type 1 diabetes and 2 patients with type 2 diabetes as IAA positive, whereas 15 patients with type 1 diabetes, 7 patients with type 2 diabetes, and 4 patients with methimazole-treated Graves' disease were identified as IAA positive using ICT-EIA. CONCLUSIONS: The ICT-EIA is an ultrasensitive and specific assay for IAA, and its use may provide a better understanding of the role of IAA in diabetes onset and progression. PMID- 22669063 TI - Looking back as we move forward. PMID- 22669064 TI - An incidentally discovered radiolucency in the posterior mandible. PMID- 22669065 TI - Risk factors for osteoradionecrosis after head and neck radiation: a systematic review. AB - OBJECTIVE: This systematic review aimed to answer the clinical question, "What is the current risk of developing osteoradionecrosis of the jaws among irradiated head and neck cancer patients?" STUDY DESIGN: A systematic review of published English-language randomized controlled trials on the outcome of radiation therapy was performed via Medline and Embase databases. Data on osteoradionecrosis/bone toxicity were collected and analyzed. RESULTS: Twenty-two articles reporting on a total of 5,742 patients were selected for final review based on strict eligibility criteria. An estimated 2% of the head and neck-irradiated patients are at risk of developing osteoradionecrosis. Patients receiving adjunctive radiotherapy, accelerated fractionation without dose reduction, and chemoradiotherapy show no increase in osteoradionecrosis risk. Accelerated fractionation with dose reduction is associated with a reduced risk, whereas hyperfractionation shows elevated risk of developing osteoradionecrosis. CONCLUSIONS: The risk of developing osteoradionecrosis among the irradiated head and neck cancer patient has significantly declined in recent years. PMID- 22669066 TI - Comparison between self-perceived and clinical oral malodor. AB - OBJECTIVES: The aims were to compare self-perceived with clinical oral malodor and to examine risk factors of oral malodor. STUDY DESIGN: The study was performed on 565 dental patients. Information on sociodemographics, dental health behavior, and self-perceived oral malodor was collected. Clinical oral malodor, oral health status, and the proteolytic activity of the N-benzoyl-DL-arginine-2 napthilamide (BANA) test in tongue coating were assessed. RESULTS: The sensitivity and specificity of self-perceived oral malodor were 47.2% and 59.2%, respectively. Risk factors for self-perceived oral malodor were smoking habit and alcohol consumption, whereas those for clinical oral malodor were level of education, dental visit frequency, tongue-brushing frequency, mouth rinse use, deep periodontal pockets, gingivitis, tongue coating, and a high BANA test score. CONCLUSIONS: Self-perception was considered an invalid method of judging one's own oral malodor. Factors related to self-perceived oral malodor were different from those found in clinical oral malodor. PMID- 22669067 TI - Enhancing the efficacy of treatment for temporomandibular patients with muscular diagnosis through cognitive-behavioral intervention, including hypnosis: a randomized study. AB - OBJECTIVE: This study evaluated the efficacy of a cognitive-behavioral therapy (CBT), including hypnosis, in patients with temporomandibular disorders (TMDs) with muscular diagnosis. STUDY DESIGN: Seventy-two patients (65 women and 7 men with an average age of 39 years) were selected according to the Research Diagnostic Criteria for TMD, and assigned to the experimental group (n = 41), receiving the 6-session CBT program, and the control group (n = 31). All patients received conservative standard treatment for TMD. The assessment included pain variables and psychologic distress. RESULTS: There were significant differences between the groups, the experimental group showing a higher improvement in the variables evaluated. Specifically, 90% of the patients under CBT reported a significant reduction in frequency of pain and 70% in emotional distress. The improvement was stable over time, with no significant differences between posttreatment and 9-month follow-up. CONCLUSIONS: CBT, including hypnosis, significantly improved conservative standard treatment outcome in TMD patients. PMID- 22669068 TI - p53 expression and mutation analysis of odontogenic cysts with and without dysplasia. AB - OBJECTIVE: Overexpression of p53 protein is well described in odontogenic cystic lesions (OCLs), including those with epithelial dysplasia; however, most p53 antibodies stain both wild-type and mutated p53 protein and may not reflect genotype. Direct sequencing of the p53 gene has not identified mutations in OCLs with dysplasia. The purpose of this study was to determine the molecular basis of p53 expression in several types of OCLs with and without dysplasia. METHODS: The study material comprised 13 OCLs: odontogenic keratocyst (n = 5), orthokeratinized odontogenic cyst (n = 5), dentigerous cyst (n = 2), lateral periodontal cyst (n = 1), and unspecified developmental odontogenic cyst (UDOC) (n = 1). Five of these had features of mild or moderate epithelial dysplasia. One intraosseous squamous cell carcinoma (SCC) that was believed to have arisen from an antecedent dysplastic orthokeratinized OC was also included. Immunohistochemistry was performed using the DO7 monoclonal antibody that recognizes wild-type and mutated p53. DNA was extracted from microdissected tissue for all samples and exons 4 to 8 of the p53 gene direct sequenced. RESULTS: In 4 of 5 OCLs with dysplasia there was strong nuclear staining of basal and suprabasal cells. In all cases without dysplasia, nuclear expression in basal cells was either negative or weak and was absent in suprabasal cell nuclei. A mutation in exon 6 of the p53 gene (E224D) was identified in both the dysplastic orthokeratinized OC and the subsequent intraosseous SCC. CONCLUSIONS: OCLs with features of dysplasia show increased expression of p53 protein that does not reflect p53 mutational status. One dysplastic OC shared the same p53 mutation with a subsequent intraosseous SCC, indicating that p53 mutation may be associated with malignant transformation in this case. PMID- 22669069 TI - Nevoid basal cell carcinoma syndrome in Indian patients: a clinical and radiological study of 6 cases and review of literature. AB - OBJECTIVE: Nevoid basal cell carcinoma syndrome (NBCCS) is rarely reported in the Indian population. We present the clinical and radiological features of 6 cases of NBCCS in Indian patients. STUDY DESIGN: The clinical and radiological features of 6 cases of NBCCS were characterized into major and minor criteria and compared with features reported in Indian patients and in patients from other parts of the world. RESULTS: The most common features seen were presence of multiple keratocystic odontogenic tumors, rib abnormalities, and calcification of falx cerebri. Talons cusp and supernumerary teeth are features not previously reported in association with NBCCS. Basal cell carcinoma was not seen in any patient. CONCLUSIONS: Combining the current series with 17 additional cases reported in Indian patients, it is evident that the frequency of clinical and radiological features in NBCCS in Indian patients differs from other ethnic groups. PMID- 22669070 TI - Chronic lingual papulosis: new, independent entity or "mature" form of transient lingual papillitis? AB - OBJECTIVE: Several acute, usually pediatric variants of edematous, symptomatic fungiform lingual papillitis have been reported since the 1990s, most notably transient lingual papillitis (TLP); but no chronic forms have been mentioned. Is there a chronic counterpart, akin to the older palatal examples of inflammatory papillary hyperplasia? The objective of this study was to clinicopathologically characterize a previously unreported entity with clustered, chronic fibrous papules (nonsyndromic) of the tongue. METHODS: Cases were collected from clinics in 2 dental schools. RESULTS: Five women and 4 men were identified with multiple, moderately firm, slightly pedunculated, normally colored masses clustered at the tip of the tongue (n = 4), covering the dorsal surface (n = 4) or on the lateral border (n = 1); 2 showed several erythematous or edematous papules (similar to TLP) admixed with fibrous papules. Patient ages ranged from 31 to 62 years (average 49) and all lesions had been present for many years. All lesions were asymptomatic except for the lateral border lesion, which presented with a burning sensation and mild tenderness (disappeared with antifungal medication). Five cases were associated with mouth breathing or a tongue-thrust habit; 4 were associated with geographic tongue or fissured tongue. Four papules were biopsied. All were composed of dense, avascular fibrous tissue with no or very few inflammatory cells; one showed focal mild neovascularity and edema. The lesion appeared to represent altered filiform papillae, more so than fungiform papillae. CONCLUSIONS: Chronic lingual papulosis (CLP) is an innocuous entity represented by focal or diffuse enlargement of numerous lingual papillae, primarily the filiform papillae. It appears to usually have an adult onset and most likely represents papillary reaction to very low-grade, chronic irritation or desiccation. Some cases with childhood onset, however, seem to be variations of normal anatomy. No treatment or biopsy is required, but a number of systemic disorders and syndromes must be ruled out before applying the CLP diagnosis. PMID- 22669071 TI - Magnetic resonance imaging (MRI) and dynamic MRI evaluation of extranodal non Hodgkin lymphoma in oral and maxillofacial regions. AB - OBJECTIVE: The purpose of this study was to evaluate the diagnostic value of magnetic resonance imaging (MRI), especially dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), in extranodal non-Hodgkin lymphoma (NHL) of oral and maxillofacial regions. STUDY DESIGN: Thirteen cases with extranodal NHL were examined using MRI. T1-weighted images (T1WI) and T2-weighted images (T2WI) or short TI inversion recovery (STIR) images were obtained in all cases. Contrast enhanced images and DCE-MRI were acquired in 10 and 7 cases, respectively. On DCE MRIs, we analyzed the parameters as follows: contrast index at maximal contrast enhancement (CImax), maximum contrast index (CI) gain/CImax ratio, and washout ratios (WR(300), WR(600), and WR(900)) at 300, 600, and 900 seconds after contrast medium injection. RESULTS: The signal intensity of all lesions was hypointense to isointense on T1WIs and showed variable contrast enhancement patterns. On T2WIs and STIR images, the signal intensity was isointense to hyperintense in almost all cases. Analysis of DCE-MRI parameters in extranodal NHLs resulted in the identification of 4 types of CI curves according to CImax and WR: (1) CImax greater than 2.0 and WR(900) greater than 40%, (2) CImax greater than 2.0 and WR(900) less than 40%, (3) CImax less than 1.5 and WR(900) greater than 40%, and (4) CImax less than 1.5 and WR(900) greater than 40%. CONCLUSIONS: The signal intensities on MRI were not specific to extranodal NHL and resembled those of other tumor types. When CImax was less than 1.5 or WR900 was less than 40%, these parameters contributed to diagnosis in extranodal NHLs. PMID- 22669072 TI - Prevalence of calcified carotid artery atheromas on the panoramic images of patients with syndrome Z, coexisting obstructive sleep apnea, and metabolic syndrome. AB - OBJECTIVES: The objective of this study was to compare the prevalence of calcified carotid artery atheromas (CCAAs) on panoramic images of individuals (n = 31) with obstructive sleep apnea (OSA) with individuals (n = 117) with syndrome Z (SZ: OSA with concomitant metabolic syndrome [MetS]). STUDY DESIGN: Images of patients with OSA or SZ referred from the Sleep Service to Dentistry were evaluated. Descriptive statistics and t tests (Bonferroni correction) were conducted to determine significant differences between atheroma prevalence and proatherogenic factors (age, apnea-hypopnea index, body mass index, lipid profile, blood pressure, glucose) between OSA and SZ groups. RESULTS: Individuals with OSA had an atheroma prevalence of 35% and those with SZ 42% (P = .52). Individuals with SZ also had significantly more severe atherogenic profiles (obesity, dyslipidemia, hyperglycemia) than OSA patients (P <= .05). Greatest CCAA prevalence (63%) was evidenced by SZ patients with severe OSA and moderate MetS. CONCLUSION: Individuals with SZ have significantly greater atherogenic burden and slightly higher prevalence of CCAAs when compared with individuals with OSA. PMID- 22669074 TI - Impact of negative frequency-dependent selection on mating pattern and genetic structure: a comparative analysis of the S-locus and nuclear SSR loci in Prunus lannesiana var. speciosa. AB - Mating processes of local demes and spatial genetic structure of island populations at the self-incompatibility (S-) locus under negative frequency dependent selection (NFDS) were evaluated in Prunus lannesiana var. speciosa in comparison with nuclear simple sequence repeat (SSR) loci that seemed to be evolutionarily neutral. Our observations of local mating patterns indicated that male-female pair fecundity was influenced by not only self-incompatibility, but also various factors, such as kinship, pollen production and flowering synchrony. In spite of the mating bias caused by these factors, the NFDS effect on changes in allele frequencies from potential mates to mating pollen was detected at the S locus but not at the SSR loci, although the changes from adult to juvenile cohorts were not apparent at any loci. Genetic differentiation and isolation-by distance over various spatial scales were smaller at the S-locus than at the SSR loci, as expected under the NFDS. Allele-sharing distributions among the populations also had a unimodal pattern at the S-locus, indicating the NFDS effect except for alleles unique to individual populations probably due to isolation among islands, although this pattern was not exhibited by the SSR loci. Our results suggest that the NFDS at the S-locus has an impact on both the mating patterns and the genetic structure in the P. lannesiana populations studied. PMID- 22669075 TI - Repetitive sequences originating from the centromere constitute large-scale heterochromatin in the telomere region in the siamang, a small ape. AB - Chromosomes of the siamang Symphalangus syndactylus (a small ape) carry large scale heterochromatic structures at their ends. These structures look similar, by chromosome C-banding, to chromosome-end heterochromatin found in chimpanzee, bonobo and gorilla (African great apes), of which a major component is tandem repeats of 32-bp-long, AT-rich units. In the present study, we identified repetitive sequences that are a major component of the siamang heterochromatin. Their repeat units are 171 bp in length, and exhibit sequence similarity to alpha satellite DNA, a major component of the centromeres in primates. Thus, the large scale heterochromatic structures have different origins between the great apes and the small ape. The presence of alpha satellite DNA in the telomere region has previously been reported in the white-cheeked gibbon Nomascus leucogenys, another small ape species. There is, however, a difference in the size of the telomere region alpha satellite DNA, which is far larger in the siamang. It is not known whether the sequences of these two species (of different genera) have a common origin because the phylogenetic relationship of genera within the small ape family is still not clear. Possible evolutionary scenarios are discussed. PMID- 22669077 TI - The proteome of erythrocyte-derived microparticles from plasma: new clues for erythrocyte aging and vesiculation. AB - Vesicle formation is an integral part of the physiological erythrocyte aging process. Recent biophysical and immunochemical data have suggested that vesicles originate by the extrusion of membrane patches that, during aging, have become damaged and simultaneously enriched in removal signals. Thereby, vesiculation may serve to postpone the untimely removal of functional cells. As a first step toward the identification of the underlying mechanisms, we isolated erythrocyte derived vesicles from plasma by fluorescence-activated cell sorting, analyzed their proteome by mass spectrometry, and compared this with the membrane proteomes of erythrocytes that were separated according to cell age. The presence of band 3 and actin in the vesicles together with the absence of almost all other integral membrane and cytoskeletal proteins, and the specific, aging-associated alterations in band 3 aggregation and degradation shown by proteomics as well as immunochemistry, all suggest that the erythrocyte aging process harbors a specific, band 3-centered mechanism for vesicle generation. The age-related recruitment of plasma proteins, proteins of the ubiquitin-proteasome system, and small G proteins to the erythrocyte membrane supports the hypothesis that modification of band 3 and/or degradation initiate vesiculation, and the subsequent recognition and fast removal of vesicles by the immune system. This article is part of a Special Issue entitled: Integrated omics. PMID- 22669076 TI - The tempo and modes of evolution of reproductive isolation in fungi. AB - Reproductive isolation is an essential ingredient of speciation, and much has been learned in recent years about the evolution of reproductive isolation and the genetics of reproductive barriers in animals and plants. Fungi have been neglected on these aspects, despite being tractable model eukaryotes. Here, we used a model fitting approach to look at the importance of different barriers to gene flow to explain the decrease of reproductive compatibility with genetic distance in fungi. We found support for the occurrence of reinforcement in the presyngamy compatibility among basidiomycetes. In contrast, no evidence for reinforcement was detected in ascomycetes, concurring with the idea that host/habitat adaptation in this group can pleiotropically cause reproductive isolation. We found no evidence of a snowballing accumulation of postsyngamic reproductive incompatibilities in either ascomycetes or the complex of anther smut fungi. Together with previous studies, our results suggest that ecologically based barriers to gene flow and karyotypic differences may have an important role in hybrid inviability and sterility in fungi. Interestingly, hybrid sterility appeared to evolve faster than hybrid inviability in fungi. PMID- 22669078 TI - The roles of the reward system in sleep and dreaming. AB - The mesolimbic dopaminergic system (ML-DA) allows adapted interactions with the environment and is therefore of critical significance for the individual's survival. The ML-DA system is implicated in reward and emotional functions, and it is perturbed in schizophrenia, addiction, and depression. The ML-DA reward system is not only recruited during wakeful behaviors, it is also active during sleep. Here, we introduce the Reward Activation Model (RAM) for sleep and dreaming, according to which activation of the ML-DA reward system during sleep contributes to memory processes, to the regulation of rapid-eye movement (REM) sleep, and to the generation and motivational content of dreams. In particular, the engagement of ML-DA and associated limbic structures prioritizes information with high emotional or motivational relevance for (re)processing during sleep and dreaming. The RAM provides testable predictions and has clinical implications for our understanding of the pathogenesis of major depression and addiction. PMID- 22669079 TI - Is the colposcopically directed punch biopsy a reliable diagnostic test in women with minor cytological lesions? AB - OBJECTIVE: The study aimed to determine the accuracy of the colposcopy-directed punch biopsy (punch) to detect or exclude high-grade cervical intraepithelial neoplasia (CIN 2 or 3) in women with atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) cytological result and minor colposcopic findings. MATERIALS AND METHODS: In a diagnostic test accuracy study, women with ASCUS or LSIL cytological result and minor colposcopic changes had a single colposcopy-targeted punch biopsy was performed immediately followed by a loop electrocautery excision procedure (LEEP) biopsy. The trial was powered to detect a level of kappa for a dichotomous outcome of 0.4 (i.e., fair-to-moderate agreement), with a two-sided significance level of 5% and a power of 90%. Accuracy parameters were computed using a cutoff for positive punch biopsy result of CIN 1+ and CIN 2+ for an outcome of CIN 2+ and CIN 3+ assessed in the LEEP specimen. RESULTS: Sixty-eight punch biopsy/LEEP paired samples were analyzed. Of the 8 CIN 3 lesions, 6 and 4 were detected at cutoff CIN 1+ and CIN 2+, respectively (sensitivity, 50% and 75%). The corresponding specificities were 65% (39/60) and 97% (58/60). The punch biopsies identified only 14 (67%) or 6 (20%) of the 21 CIN 2+ lesions at cutoff CIN 1+ or CIN 2+, respectively. Of the punch biopsies, 31 (45.6%) accurately detected the severity of cervical abnormality. CONCLUSIONS: A single colposcopically directed punch biopsy appears to be insufficient to exclude underlying CIN 2 or 3. PMID- 22669080 TI - Effect of long-term cannabis use on axonal fibre connectivity. AB - Cannabis use typically begins during adolescence and early adulthood, a period when cannabinoid receptors are still abundant in white matter pathways across the brain. However, few studies to date have explored the impact of regular cannabis use on white matter structure, with no previous studies examining its impact on axonal connectivity. The aim of this study was to examine axonal fibre pathways across the brain for evidence of microstructural alterations associated with long term cannabis use and to test whether age of regular cannabis use is associated with severity of any microstructural change. To this end, diffusion-weighted magnetic resonance imaging and brain connectivity mapping techniques were performed in 59 cannabis users with longstanding histories of heavy use and 33 matched controls. Axonal connectivity was found to be impaired in the right fimbria of the hippocampus (fornix), splenium of the corpus callosum and commissural fibres. Radial and axial diffusivity in these pathways were associated with the age at which regular cannabis use commenced. Our findings indicate long-term cannabis use is hazardous to the white matter of the developing brain. Delaying the age at which regular use begins may minimize the severity of microstructural impairment. PMID- 22669081 TI - Structural substrates for resting network disruption in temporal lobe epilepsy. AB - Magnetic resonance imaging methods that measure interregional brain signalling at rest have been advanced as powerful tools to probe organizational properties of functional networks. In drug-resistant temporal lobe epilepsy, resting functional magnetic resonance imaging studies have primarily employed region of interest approaches that preclude a comprehensive evaluation of large-scale functional interactions. In line with the distributed nature of structural damage in this condition, we set out to quantify connectivity across the entire range of resting networks. Furthermore, we assessed whether connectivity is driven by co-localized structural pathology. We obtained resting state, diffusion tensor and anatomical imaging data in 35 patients with temporal lobe epilepsy and 20 healthy subjects on a 3 T scanner. Resting state networks were identified using independent component analysis, which allows an objective whole-brain quantification of functional connectivity. We performed group comparisons before and after correcting for voxel-wise grey matter density. In addition, we identified voxel wise associations between resting connectivity and white matter coherence indexed by fractional anisotropy. Compared with controls, patients showed altered (typically reduced) functional connectivity between the hippocampus, anterior temporal, precentral cortices and the default mode and sensorimotor networks. Reduced network integration of the hippocampus was explained by variations in grey matter density, while functional connectivity of the parahippocampus, and frontal and temporal neocortices showed atypical associations with white matter coherence within pathways carrying connections of these regions. Our multimodal imaging study suggests that in temporal lobe epilepsy, cortical atrophy and microstructural white matter damage impact functional resting connectivity. PMID- 22669083 TI - Ultrasensitive detection of the reduced form of nicotinamide adenine dinucleotide based on carbon nanotube field effect transistor. AB - We developed a simple, ultrasensitive, and quantitative detection method for the reduced form of nicotinamide adenine dinucleotide (NADH), based on carbon nanotube field effect transistors (CNTFETs). Following the injection of NADH at different concentrations, we obtained different electrical signals from a semiconductor characterization system mimicking biological catalysis of NADH dehydrogenase (CoI). Here, FET was fabricated via photolithography, attaching silicon wells, as the detection chamber, on the channel area of the single wall carbon nanotube (SWCNT). SWCNTs were functionalized with phenazine derivant, a counterpart of the key functional prosthetic group of CoI enzyme. In the presence of NADH, electrons transferred to phenazine derivant through SWCNT, by analogous means of the electron transport chain formed by a series of iron-sulfur (FeS) clusters in CoI. Using this method, the limit of detection was as low as 1 pM, and the range of linear response was 10 pM to 500 nM. Significantly, this approach possesses great potential for applications in real-time detection of NADH at extremely low concentrations, and rigorous analysis for NADH in electrochemical fields. PMID- 22669084 TI - Beer potomania: drink in this atypical cause of hyponatremia. PMID- 22669082 TI - The differing roles of the frontal cortex in fluency tests. AB - Fluency tasks have been widely used to tap the voluntary generation of responses. The anatomical correlates of fluency tasks and their sensitivity and specificity have been hotly debated. However, investigation of the cognitive processes involved in voluntary generation of responses and whether generation is supported by a common, general process (e.g. fluid intelligence) or specific cognitive processes underpinned by particular frontal regions has rarely been addressed. This study investigates a range of verbal and non-verbal fluency tasks in patients with unselected focal frontal (n=47) and posterior (n=20) lesions. Patients and controls (n=35) matched for education, age and sex were administered fluency tasks including word (phonemic/semantic), design, gesture and ideational fluency as well as background cognitive tests. Lesions were analysed by standard anterior/posterior and left/right frontal subdivisions as well as a finer-grained frontal localization method. Thus, patients with right and left lateral lesions were compared to patients with superior medial lesions. The results show that all eight fluency tasks are sensitive to frontal lobe damage although only the phonemic word and design fluency tasks were specific to the frontal region. Superior medial patients were the only group to be impaired on all eight fluency tasks, relative to controls, consistent with an energization deficit. The most marked fluency deficits for lateral patients were along material specific lines (i.e. left-phonemic and right-design). Phonemic word fluency that requires greater selection was most severely impaired following left inferior frontal damage. Overall, our results support the notion that frontal functions comprise a set of specialized cognitive processes, supported by distinct frontal regions. PMID- 22669087 TI - Nanomedicine: Downsizing tumour therapeutics. PMID- 22669085 TI - Insufficient androgen and FSH signaling may be responsible for the azoospermia of the infantile primate testes despite exposure to an adult-like hormonal milieu. AB - BACKGROUND: In humans, as well as in other higher primates, the infantile testis is exposed to an adult-like hormonal milieu, but spermatogenesis is not initiated at this stage of primate development. In the present study, we examined the molecular basis of this intriguing infertile state of the primate testis. METHODS: The integrity of androgen receptor (AR) and FSH receptor (FSHR) signaling pathways in primary cultures of Sertoli cells (Scs) harvested from azoospermic infant and spermatogenic pubertal monkey testes were investigated under identical in vitro hormonal conditions. In order to synchronously harvest Scs from early pubertal testis, the activation of testicular puberty was timed experimentally by prematurely initiating gonadotrophin secretion in juvenile animals with an intermittent infusion of gonadotrophin-releasing hormone. RESULTS: While qRT-PCR demonstrated that AR and FSHR mRNA expression in Scs from infant and pubertal testes were comparable, androgen-binding and FSH-mediated cAMP production by infant Scs was extremely low. Compromised AR and FSHR signaling in infant Scs was further supported by the finding that testosterone (T) and FSH failed to augment the expression of the T responsive gene, claudin 11, and the FSH responsive genes, inhibin-betaB, stem cell factor (SCF) and glial cell line-derived neurotrophic factor (GDNF) in Scs harvested at this stage of development. CONCLUSION: These results indicate that compromised AR and FSHR signaling pathways in Scs underlie the inability of the infant primate testis to respond to an endogenous hormonal milieu that later in development, at the time puberty, stimulates the initiation of spermatogenesis. This finding may have relevance to some forms of idiopathic infertility in men. PMID- 22669088 TI - Biosensors: One molecule at a time. PMID- 22669089 TI - Photodetectors: A sensitive pair. PMID- 22669090 TI - Plaque-infiltrating T lymphocytes in patients with carotid atherosclerosis: an insight into the cellular mechanisms associated to plaque destabilization. AB - AIM: Inflammation plays a crucial role in the progression of atherosclerotic plaques. The aim of the present study was to investigate phenotypic and functional characteristics of plaque-infiltrating T lymphocytes associated with a complicated phenotype of carotid atherosclerotic lesions. METHODS: Atherosclerotic plaques were obtained from 17 patients undergoing carotid endarterectomy and cultured to isolate infiltrating T lymphocytes. Blood samples were obtained from patients and from 20 sex- and age-matched healthy subjects. The presence of lymphocytes (CD3+ cells) within atherosclerotic plaques was determined by immunohistochemistry. Phenotypic characteristics and intracellular cytokine expression of plaque-infiltrating and circulating T lymphocytes were determined by flow cytometry. Cytokine levels in supernatants from infiltrating T cell cultures were evaluated by enzyme-linked immunosorbent assay. RESULTS: A higher number of CD3+ cells was detected in complicated than in uncomplicated plaques. Complicated plaques had higher percentages of tumor necrosis factor (TNF)-alpha- and interferon (IFN)-gamma- positive cells than uncomplicated ones, especially in CD4+ subpopulation. In patients the percentages of TNF-alpha positive cells were higher in infiltrating than in circulating lymphocyte samples. Intracellular TNF-alpha, IFN-gamma, interleukin (IL)-4 and IL-10 expression resulted higher in circulating lymphocyte samples from patients than in those from healthy subjects. Supernatants of infiltrating T cell cultures from complicated plaques showed higher levels of TNF-alpha and lower levels of IL-4 than those from uncomplicated plaques. CONCLUSION: Our data provide new information on the presence of increased percentages of pro-inflammatory T lymphocytes in complicated plaques with respect to uncomplicated ones and support the concept of the key role played by activated T cells in the progression of atherosclerotic lesions. PMID- 22669091 TI - Long-term outcome after acute type A aortic dissection: does an age limit still exist? AB - AIM: Aim of the study was to analyze outcome in patients who underwent surgery following type A aortic dissections and to evaluate the long-term survival rates in patients 70 years of age and older and those under 70 years of age, and in males as compared to females. METHODS: Between September 1997 and October 2008, 154 patients were retrospectively enrolled. There were 102 males (66.2%) and 52 females (33.8%) with a mean age of 63.5+/-12; seven patients (4.5%) were over 80 years of age, 46 (29.8%) were between 70 and 80 years of age and 101 were under 70 years of age at the time of surgery. We compared patients 70 years of age and older with those under 70 years of age, analyzing the early and long-term survival results and postoperative complications. RESULTS: Overall in-hospital mortality was 17.5% and permanent neurological dysfunction occurred in 10 patients (6.5%). Twenty patients (12.9%) died during follow-up. Among the males, the long-term survival rate was 80%, 68% and 51% at 1, 5 and 10 years, respectively. Among the females, survival rate was 84.6%, 72.3% and 47.5% at 1, 5 and 10 years, respectively. Five- and 10-year survival rates were 78.1% and 59.4%, respectively, for patients under 70 years of age, and 50.8% at 5 years and 26.1% at 10 years for those over 70. CONCLUSION: Patients might not be excluded from surgical intervention for acute type A aortic dissection (ATAAD) only due to age. It is important to consider biological age and the clinical features of the patients at the time of surgery. Age is a relative but not absolute contraindication for surgery in ATAAD. Long-term survival was not statistically different between males and females. PMID- 22669092 TI - Morphological, immunohistochemical and biochemical effects of non-pulsatile ex vivo perfusion with crescent pressures in human saphenous veins. AB - AIM: On the average, 15% to 25% of peripheral grafts and 10% to 30% of coronary grafts fail within 5 years. Changes in mechanical forces to which the vein is subjected could be an explanation for this phenomenon. We submitted human saphenous vein segments to non-pulsatile ex vivo perfusion with crescent pressures and evaluated morphology, nitric oxide synthase immunohistochemical expression; tissue levels of nitrite/nitrate and oxidative stress products. METHODS: Intact segments of human saphenous veins were obtained from 30 patients submitted to elective coronary artery bypass graft surgery. Ex vivo perfusion was performed during 3 hours, using oxygenated Krebs solution, flow of 100 mL/min and pressures of 0, 50, 100, 200 and 300 mmHg, defining five groups. RESULTS: Optical microscopy showed that veins of groups perfused with 200 and 300 mmHg presented increased luminal area and endothelial denuding. Electron microscopy transmission showed alterations in veins perfused with 200 and 300 mmHg. Immunohistochemical expression of the three nitric oxide synthase isoforms was observed in all vein layers, without significant difference among groups. Tissue levels of nitrite/nitrate were not significantly different among distinctive perfusion. Nitrotyrosine was not immunohistochemically expressed in all veins and malondialdehyde tissue levels were not different among groups. CONCLUSION: Non pulsatile ex vivo perfusion during 3h caused morphological alterations in human saphenous veins (HSVs), which were not accompanied by immunohistochemical and biochemical alterations. Even with mechanical lesions, HSVs maintained the ability of express nitric oxide synthase (NOS) and release nitric oxide. PMID- 22669093 TI - Transcranial Doppler and diffusion-weighted magnetic resonance evaluation of cerebral embolization occurring during transfemoral carotid stenting with proximal flow blockage. AB - AIM: Transfemoral carotid artery stenting (CAS) with endovascular proximal flow blockage is deemed able to reduce the cerebral embolization observed during filter-protected CAS. We evaluated clinical outcome and intraoperative embolization rates, measured by diffusion-weighted magnetic resonance imaging (DW MRI) and transcranial Doppler monitoring, in a series of patients undergoing CAS with proximal flow blockage. METHODS: A series of 35 consecutive patients with symptomatic or asymptomatic internal carotid artery stenosis >=70% were included to undergo CAS with proximal flow blockage, obtained with the Mo.Ma system. All patients underwent preoperative and postoperative DW-MRI in order to detect new ischemic lesions. Of the 35 patients, 31 (89%) underwent intraoperative transcranial Doppler monitoring to record the microembolic signals (MES) produced during each procedure. RESULTS: The MoMa system was successfully used in 34 patients (technical success: 97%). Intolerance to balloon occlusion was observed in 4 patients (12%), but never compromised the completion of the procedure. No deaths or neurological events occurred in the postoperative period. DW-MRI disclosed 74 new ischemic lesions in 8 patients (8/34, 23.5%). All lesions except one were ipsilateral to the treated carotid artery. MES were detected in all procedures, with a mean number of 33.2+/-23.2 (range 3-103). In 20 procedures (20/31, 65%), MES were detected also during flow blockage (mean: 9.1+/-7; range 2 28). CONCLUSION: While achieving good technical and clinical results, CAS with proximal flow blockage is still accompanied by a non-negligible cerebral embolization. The detection of MES during ICA flow blockage suggests the need for a better selection of patients. PMID- 22669094 TI - MitroFast(r) annuloplasty ring for complete posterior mitral leaflet destruction: a novel approach in active endocarditis. AB - We report the successful use of MitroFast(r) annuloplasty ring in the setting of active endocarditis to preserve the native valve mechanism despite complete posterior leaflet destruction. This patient remained well at 20 month follow-up after her surgery. PMID- 22669095 TI - Thrombin injection and compression with removable guidewire in the treatment of postcatheterization femoral pseudoaneurysm. AB - AIM:The purpose of our study was to determine the efficacy of percutaneous thrombin treatment for iatrogenic femoral artery pseudoaneurysms (FAP) and to identify those criteria that may help to predict increased treatment failure risk and complications. METHODS: A number of 32 iatrogenic femoral pseudoaneurysms were treated with US-guided thrombin injection (group A), while four elderly patient with complex femoral pseudoaneurysm underwent compression assisted by removable "guidewire" (group B). Twenty-five were classified as simple (single lobe) and 11 as complex (at least two lobes with a single neck to the native vessel). Pseudoaneurysm volume, classification, thrombin dose, anticoagulation therapy status, and sheath size were considered independent prognostic factors. RESULTS: All the 36 patients (pts) had initial complete femoral pseudoaneurysms thrombosis. The aneurysm was thrombosed on a Doppler ultrasound (US) follow-up in all the cases but four (group A), those who required the additional thrombin injection. A fatal complication occurred in one patient with complex FAP (group A). CONCLUSION: Preliminary data suggest that US-guided percutaneous thrombin injection is a safe and effective method to treat iatrogenic pseudoaneurysms. Simple iatrogenic femoral pseudoaneurysms benefit a single injection of up to 500 units of topical thrombin. We recommend more caution in complex pseudoaneurysms treatment; it is preferable to perform thrombin injection first into the lobe which is not directly joined to the femoral artery. A longer bed rest and closer observation are mandatory during the subsequent 24 hours. If the lobe communicating with the femoral artery is still patent, it can be retreated. Alternatively, we propose a new strategy approach through compression assisted removable "guidewire". PMID- 22669096 TI - Early outcomes of intra-aortic balloon pump in cardiac surgery. AB - AIM: As the proportion of high-risk patients for cardiac surgery increases, use of intraaortic balloon pump (IABP) has increased, especially for acute heart failure following cardiac surgery. The aim of this prospective study was to determine risk factors of early mortality and IABP complications in patient who underwent cardiac surgery. METHODS: From March 2008 through February 2011, 106 (2.36%) patients received preoperative (N.=19) and postoperative IABP (N.=87). They included 68 (64.2%) men and 38 (35.8%) women, with a mean age 59 +/- 9.6 years. Most of patients only had coronary disease. (N.=73) Prospective data collection obtained. RESULTS: Fifty nine patients (59.7%) were successfully weaned from IABP support and survived to hospital discharge. Hospital mortality was 44.3%. Risk factors for hospital death were age, urgent procedure, cardiopulmonary bypass (CPB) time, and incomplete revascularization. The overall mortality between patients with preoperative IABP insertion and patients with postoperative IABP did not significantly differ (6/19 vs. 41/87, P=0.163). Early vascular complications occurred in 4 patients (3.8%) that were not significant. CONCLUSION: The use of IABP is a safe option to support heart failure in cardiac surgery. Improved IABP technology and better surveillance have lead to increased use with lower complication rates. PMID- 22669097 TI - Lung volume reduction surgery 10 years later. AB - AIM:The purpose of this study was to evaluate whether favorable short-term results in term of functional outcome and survival following lung volume reduction surgery persist for longer periods. Composite preoperative and early postoperative variables were analysed. METHODS: This study was conducted on 52 emphysematous patients who underwent lung volume reduction surgery (LVRS) from 1993 to 2000, through a delayed retrospective analysis that has allowed us to evaluate a long-term follow-up (10 years or more); lung function and other variables were considered with respect to survival; 11 patients submitted to lung transplantation were also evaluated. RESULTS:Upper lobe distribution of emphysema (P=0.02, HR:2.43) and systolic PAP (P=0.04, HR=2.11) were significantly correlated to survival in a multivariate analysis; these variables seem to identify a small subgroup of 14 patients with longer survival (more than 10 years). Lung transplantation performed in some worsening patients (mean FEV1%:17+/-4) showed a trend of better survival when we compared the observed survival (55+/-47 months) with expected survival (39.5+/-15 months) (P=ns). CONCLUSION: We conclude that LVRS can lead to a very long survival (10 years or more) in a small subgroup of patients, with improvement of pulmonary functional data. Some preoperative data (upper lobe distribution of emphysema and pulmonary arterial pressure) appear to predict survival. Lung transplantation can be offered to these patients, showing a trend to improved life expectancy. PMID- 22669098 TI - In vitro effects of lidocaine hydrochloride on coronary artery bypass grafts. AB - AIM: Coronary artery bypass grafting (CABG) is one of the most common procedures performed to improve blood supply to myocardium. The characteristics of grafts, mechanical stress and pharmacological agents have substantial influence on the short and long term graft patency. Lidocaine is among the most frequently used antiarrhythmic agents perioperatively. The aim of this study was to evaluate the in vitro effects of lidocaine on internal mammarian artery (IMA), radial artery (RA) and saphenous vein (SV) grafts. METHODS: Using standard tissue bath techniques, responses to increasing concentrations of lidocaine hydrochloride were obtained, in segments of IMA, RA and SV grafts. Twenty patients were enrolled in the study with a total number of 48 grafts (16 for IMA, RA and SV grafts each). In vitro lidocaine concentrations between 10(-9)M and 10(-3.5)M were studied to represent therapeutic plasma concentration of 1.5-5 mcg/mL. RESULTS: In IMA and RA grafts, lidocaine hydrochloride caused vasodilatation (40.5+/-1.9% and 39.1+/-2.6 % respectively) at concentrations between 10(-9) to 10(-7.5) M while causing a dose dependent vasoconstriction response at concentrations above 10(-7.5) M. In SV graft samples, lidocain hydrochloride caused vasodilatation (24.4+/-1.9 %) at concentrations between 10(-9) to 10(-7) M while causing dose dependent vasoconstriction at concentrations above 10(-7) M. For vasoconstriction effect, mean+/-SD values for E(max) were calculated as: 120.1+/-6.6% in IMA, 83.35+/-5.06% in RA, and 154.0+/-13.8% in SV. The vasoconstriction in the SV samples was higher than in the RA and IMA. The mean +/ SD LogEC(50) values were -5.15+/-0.27, -5.76+/-0.11 and -5.56+/-0.19 for SV, IMA and RA grafts respectively.) There was a statiscally significant differences in the Log EC(50) values between SV, IMA and RA (P<0.005) CONCLUSION: Based on the results of our study, we conclude that, increasing doses of lidocaine in the perioperative period may cause vasospasm in IMA, RA and SV grafts. Thus, avoiding high doses may have a role in improving perioperative and long term mortality. PMID- 22669099 TI - Stepwise valve deployment decreases the risk of incorrect valve positioning during transapical aortic valve implantation. PMID- 22669100 TI - Pulmonary hypertension is associated with higher mortality in cystic fibrosis patients awaiting lung transplantation. AB - AIM:Pulmonary hypertension (PH) is frequently found in patients with advanced parenchymal lung diseases. In advanced stages, cystic fibrosis (CF) patients can develop PH and eventually cor pulmonale. Little is known about the prevalence of PH in CF patients and its impact on outcome. METHODS: We retrospectively studied a large cohort of CF patients evaluated for lung transplantation between 1995 and 2010. All the patients underwent right heart catheterization as part of the evaluation. We included 179 unique consecutive adult CF patients. Age was 24+/-9 years and 45.8% were women. RESULTS:Eighty-seven patients were transplanted (48.6%) and 65 died (36.3%) while waiting for LT. By right heart catheterization, 38.5% of the patients had PH (mean >=25 mm Hg). PaCO2 (P=0.045) and forced vital capacity (P=0.023) were independent predictors of PH in CF patients. The median survival (free of lung transplantation) was 13.4 months. After adjusting for several covariates, the presence of PH significantly increased mortality (hazard ratio, HR) (P<0.001). Pulmonary vascular resistance was associated with mortality (P=0.03). When both PH and PVR were included in the model, only PH predicted mortality. CONCLUSION: Pulmonary hypertension of mild degree is frequently found in CF patients with advanced lung disease and its presence significantly worsens survival. PMID- 22669101 TI - Influence of skin model on in vitro performance of drug-loaded soluble microneedle arrays. AB - A plethora of studies have described the in vitro assessment of dissolving microneedle (MN) arrays for enhanced transdermal drug delivery, utilising a wide variety of model membranes as a representation of the skin barrier. However, to date, no discussion has taken place with regard to the choice of model skin membrane and the impact this may have on the evaluation of MN performance. In this study, we have, for the first time, critically assessed the most common types of in vitro skin permeation models - a synthetic hydrophobic membrane (Silescol((r)) of 75 MUm) and neonatal porcine skin of definable thickness (300 350 MUm and 700-750 MUm) - for evaluating the performance of drug loaded dissolving poly (methyl vinyl ether co maleic acid) (PMVE/MA) MN arrays. It was found that the choice of in vitro skin model had a significant effect on the permeation of a wide range of small hydrophilic molecules released from dissolving MNs. For example, when Silescol((r)) was used as the model membrane, the cumulative percentage permeation of methylene blue 24h after the application of dissolvable MNs was found to be only approximately 3.7% of the total methylene blue loaded into the MN device. In comparison, when dermatomed and full thickness neonatal porcine skin were used as a skin model, approximately 67.4% and 47.5% of methylene blue loaded into the MN device was delivered across the skin 24h after the application of MN arrays, respectively. The application of methylene blue loaded MN arrays in a rat model in vivo revealed that the extent of MN-mediated percutaneous delivery achieved was most similar to that predicted from the in vitro investigations employing dermatomed neonatal porcine skin (300-350 MUm) as the model skin membrane. On the basis of these results, a wider discussion within the MN community will be necessary to standardise the experimental protocols used for the evaluation and comparison of MN devices. PMID- 22669102 TI - The application of serum cystatin C in estimating the renal function in women with preeclampsia. AB - OBJECTIVE: Serum cystatin C (Cys-C) is known to reflect the glomerular filtration rate (GFR) more precisely in native kidney diseases and renal dysfunctions secondary to other diseases. This study investigated the serum Cys-C in estimating the renal function in preeclamptic women. METHODS: A total of 96 patients with normal pregnancy (controls) and 48 cases of severe preeclampsia were recruited in this study. We measured the 24-hour creatinine clearance (CrCl), serum creatinine, Cys-C, uric acid (UA), and beta trace protein (BTP) concentrations on all the pregnant women in the second trimester and third trimester and in the postpartum of the patients with severe preeclampsia. Multiple comparisons and correlation analysis were used to analyze the indexes estimating the GFR. RESULTS: In the normal pregnancies, the concentrations of serum creatinine, UA, and BTP were significantly higher in the third trimester compared to the second trimester, however with no significant differences in the serum Cys-C levels. Comparison between the second and third trimester in patients with severe preeclampsia indicated that significant difference existed in the serum Cys-C, with higher concentration in third trimester. Correlation analyses demonstrated that significant negative correlations could be detected between Cys C and 24-hour CrCl in the second trimester and third trimester of all the 144 pregnant women and in the postpartum of the patients with severe preeclampsia, and better correlations in normal participants than in participants with preeclampsia. CONCLUSIONS: Serum Cys-C seems to reflect the GFR precisely in women with severe preeclampsia and can be a good marker to monitor the renal function from antepartum to postpartum. PMID- 22669103 TI - The value of cell line validation. PMID- 22669104 TI - In regard to Lassman et al. PMID- 22669106 TI - Macrocyclic ligand encapsulating dysprosium triangles: axial ligands perturbed magnetic dynamics. AB - Two Dy(3) triangles encapsulated inside the cavity of a macrocycle ligand have been successfully synthesized, providing a unique opportunity to probe the relaxation dynamics of the complexes by altering the axial ligands. PMID- 22669108 TI - Impact versus impact factor and Eigenfactor. PMID- 22669107 TI - Yin-Yang1 is required for epithelial-to-mesenchymal transition and regulation of Nodal signaling during mammalian gastrulation. AB - The ubiquitously expressed Polycomb Group protein Yin-Yang1 (YY1) is believed to regulate gene expression through direct binding to DNA elements found in promoters or enhancers of target loci. Additionally, YY1 contains diverse domains that enable a plethora of protein-protein interactions, including association with the Oct4/Sox2 pluripotency complex and Polycomb Group silencing complexes. To elucidate the in vivo role of YY1 during gastrulation, we generated embryos with an epiblast specific deletion of Yy1. Yy1 conditional knockout (cKO) embryos initiate gastrulation, but both primitive streak formation and ingression through the streak is severely impaired. These streak descendants fail to repress E Cadherin and are unable to undergo an appropriate epithelial to mesenchymal transition (EMT). Intriguingly, overexpression of Nodal and concomitant reduction of Lefty2 are observed in Yy1 cKO embryos, suggesting that YY1 is normally required for proper Nodal regulation during gastrulation. Furthermore, definitive endoderm is specified but fails to properly integrate into the outer layer. Although anterior neuroectoderm is specified, mesoderm production is severely restricted. We show that YY1 directly binds to the Lefty2 locus in E7.5 embryos and that pharmacological inhibition of Nodal signaling partially restores mesoderm production in Yy1 cKO mutant embryos. Our results reveal critical requirements for YY1 during several important developmental processes, including EMT and regulation of Nodal signaling. These results are the first to elucidate the diverse role of YY1 during gastrulation in vivo. PMID- 22669109 TI - Cobalt-based dental alloy, allergy to cobalt, and palmoplantar pustulosis. PMID- 22669111 TI - Slow-growing gingival mass. AB - OBJECTIVES: A 33-year-old woman presented with a slow growing palatal gingival mass. The clinical differential diagnosis included benign tumors and tumor-like lesions, including the pyogenic granuloma, peripheral giant cell granuloma, peripheral ossifying fibroma, giant cell fibroma, peripheral odontogenic tumors, and oral focal mucinosis. STUDY DESIGN: The lesion was excised and histopathological examination followed by immunohistochemical staining was carried out. RESULTS: The microscopic findings and the immunohistochemical reactivity was diagnostic for a nerve sheath myxoma. CONCLUSIONS: The clinical features, microscopic findings, immunohistochemistry, and the differential diagnosis including the relationship to the neurothekeoma are discussed. PMID- 22669112 TI - Gingival bleeding and jaw bone necrosis in patients with metastatic renal cell carcinoma receiving sunitinib: report of 2 cases with clinical implications. AB - There is emerging evidence that oral mucositis/stomatitis is a common adverse effect of sunitininb antiangiogenic therapy in patients with metastatic renal cell carcinoma (mRCC). In addition, a case of sunitinib-related jaw osteonecrosis was recently described. We report on 2 patients with mRCC treated with sunitinib. The first patient, a 19-year-old woman, treated with cisplatin and sunitinib, presented with oral pain, malodor, spontaneous and continuous gingival bleeding, and painful necrotic ulcerations clinically resembling necrotizing ulcerative gingivitis (NUG). Suntinib-related stomatitis and bleeding were considered cumulative to NUG symptoms. The second patient, a 64-year-old woman, treated with sunitinib only, complained of mandibular pain. Sunitinib-related jaw osteonecrosis was diagnosed. Gingival bleeding and soft tissue necrosis, as well as jaw osteonecrosis may develop as adverse events of sunitinib use. Antiangiogenic therapies are increasingly used in the treatment of cancers. The presented cases are aimed to alert health care professionals on adverse oral events. PMID- 22669113 TI - Mucocutaneous dyskeratosis with periodontal destruction and premature tooth loss. AB - We report the case of a 16-month-old boy who presented an exuberant erythematous gingival swelling and severe tooth mobility. Radiographic examination confirmed alveolar bone loss, and gingival biopsy showed epithelium containing numerous dyskeratotic cells. Because of feeding difficulties, the enlarged gingival tissue and involved teeth were removed. One year later, similar problems were encountered during the eruption of the deciduous second molars. The patient also exhibited papular skin lesions. Histopathologic features on biopsies of the skin and oral lesions were similar. The oral and cutaneous lesions presented by this patient were similar to those described by From et al. in 1978 in a father and son, reported as dyskeratosis benigna intraepithelialis mucosae et cutis hereditaria--the sole report in the English language. To avoid confusion with hereditary benign intraepithelial dyskeratosis (Witkop-von Sallmann syndrome) we have renamed the condition as mucocutaneous dyskeratosis with periodontal destruction and tooth loss. PMID- 22669114 TI - Facial necrotizing fasciitis from an odontogenic infection. AB - Necrotizing fasciitis (NF) is defined as rapidly progressive necrosis of subcutaneous fat and fascia. It is a rare but life-threatening infection characterized by a progressive, usually rapid, necrotizing process of the subcutaneous tissues and fascial planes. The condition is commonly described in the extremities, abdominal wall, and perineum but rarely seen in the head and neck. The diagnosis of NF depends mainly on clinical features, which are not always observable, so that the disease is often diagnosed late in its course, resulting in high mortality. Broad-spectrum antibiotics, aggressive surgical treatment and supportive therapy are the most widely accepted modalities of successful treatment. We describe a case of necrotizing fasciitis of the head and neck, arising from odontogenic origin. PMID- 22669115 TI - Cracks in dentin and enamel after cryopreservation. AB - OBJECTIVE: The objective of this study was to investigate if cryopreservation of teeth for long-term storage leads to cracks in enamel and dentin. STUDY DESIGN: Three teeth, which were extracted for orthodontic reasons, were cryopreserved in liquid nitrogen (temperature -196 degrees C) and thawed according to standard protocols after 4 months. Micro computed tomography using synchrotron radiation was performed to detect cracks in the tooth hard tissues. RESULTS: Cracks were found in the enamel of all teeth, which are associated with forceps application during extraction. Cracks with a width larger than 0.8 MUm were not identified in dentin and cementum. CONCLUSION: Although cryopreservation of teeth according to the standard protocol does not generate cracks more than 0.8 MUm wide, the use of forceps can result in prominent cracks. PMID- 22669116 TI - [7]-Helicene: a chiral molecular tweezer for silver(I) salts. AB - We have unambiguously demonstrated the binding of the silver(I) ion in the central cavity of [7]-helicene, given that the counterion is weakly coordinating. In such a binding mode, the helicene is functioning as a chiral molecular tweezer. PMID- 22669117 TI - Roles of vimentin and 14-3-3 zeta/delta in the inhibitory effects of heparin on PC-3M cell proliferation and B16-F10-luc-G5 cells metastasis. AB - AIM: To investigate the inhibitory effects of heparin on PC-3M cells proliferation in vitro and B16-F10-luc-G5 cells metastasis in Balb/c nude mice and identify the protein expression patterns to elucidate the action mechanism of heparin. METHODS: Human prostate cancer PC-3M cells were incubated with heparin 0.5 to 125 MUg/mL for 24 h. The proliferation of PC-3M cells was assessed by MTS assay. BrdU incoporation and Ki67 expression were detected using a high content screening (HCS) assay. The cell cycle and apoptosis of PC-3M cells were tested by flow cytometry. B16-F10-luc-G5 cardinoma cells were injected into the lateral tail vein of 6-week old male Balb/c nude mice and heparin 30 mg/kg was administered iv 30 min before and 24 h after injection. The metasis of B16-F10 luc-G5 cells was detected by bioluminescence assay. Activated partial thromboplastin time (APTT) and hemorheological parameters were measured on d 14 after injection of B16-F10-luc-G5 carcinoma cells in Balb/c mice. The global protein changes in PC-3M cells and frozen lung tissues from mice burdened with B16-F10-luc-G5 cells were determined by 2-dimensional gel electrophoresis and image analysis. The protein expression of vimentin and 14-3-3 zeta/delta was measured by Western blot. The mRNA transcription of vimentin, transforming growth factor (TGF)-beta, E-cadherin, and alpha(v)-integrin was measured by RT-PCR. RESULTS: Heparin 25 and 125 MUg/mL significantly inhibited the proliferation, arrested the cells in G(1) phase, and suppressed BrdU incorporation and Ki67 expression in PC-3M cells compared with the model group. But it had no significant effect on apoptosis of PC-3M cells. Heparin 30 mg/kg markedly inhibits the metastasis of B16-F10-luc-G5 cells on day 8. Additionally, heparin administration maintained relatively normal red blood hematocrit but had no influence on APTT in nude mice burdened with B16-F10-luc-G5 cells. Thirty of down regulated protein spots were identified after heparin treatment, many of which are related to tumor development, extracellular signaling, energy metabolism, and cellular proliferation. Vimentin and 14-3-3 zeta/delta were identified in common in PC-3M cells and the lungs of mice bearing B16-F10-luc-G5 carcinoma cells. Heparin 25 and 125 MUg/mL decreased the protein expression of vimentin and 14-3-3 zeta/delta and the mRNA expression of alpha(v)-integrin. Heparin 125 MUg/mL decreased vimentin and E-cadherin mRNA transcription while increased TGF-beta mRNA transcription in the PC-3M cells, but the differences were not significant. Transfection of vimentin-targeted siRNA for 48 h significantly decreased the BrdU incoporation and Ki67 expression in PC-3M cells. CONCLUSION: Heparin inhibited PC 3M cell proliferation in vitro and B16-F10-luc-G5 cells metastasis in nude mice by inhibition of vimentin, 14-3-3 zeta/delta, and alpha(v)-integrin expression. PMID- 22669118 TI - Population pharmacokinetics modeling of levetiracetam in Chinese children with epilepsy. AB - AIM: To establish a population pharmacokinetics (PPK) model of levetiracetam in Chinese children with epilepsy. METHODS: A total of 418 samples from 361 epileptic children in Peking University First Hospital were analyzed. These patients were divided into two groups: the PPK model group (n=311) and the PPK validation group (n=50). Levetiracetam concentrations were determined by HPLC. The PPK model of levetiracetam was established using NONMEM, according to a one compartment model with first-order absorption and elimination. To validate the model, the mean prediction error (MPE), mean squared prediction error (MSPE), root mean-squared prediction error (RMSPE), weight residues (WRES), and the 95% confidence intervals (95% CI) were calculated. RESULTS: A regression equation of the basic model of levetiracetam was obtained, with clearance (CL/F)=0.988 L/h, volume of distribution (V/F)=12.3 L, and K(a)=1.95 h(-1). The final model was as follows: K(a)=1.56 h(-1), V/F=12.1 (L), CL/F=1.04*(WEIG/25)(0.583) (L/h). For the basic model, the MPE, MSPE, RMSPE, WRES, and the 95%CI were 9.834 (-0.587 197.720), 50.919 (0.012-1286.429), 1.680 (0.021-34.184), and 0.0621 (-1.100 1.980). For the final model, the MPE, MSPE, RMSPE, WRES, and the 95% CI were 0.199 (-0.369-0.563), 0.002082 (0.00001-0.01054), 0.0293 (0.001-0.110), and 0.153 (-0.030-1.950). CONCLUSION: A one-compartment model with first-order absorption adequately described the levetiracetam concentrations. Body weight was identified as a significant covariate for levetiracetam clearance in this study. This model will be valuable to facilitate individualized dosage regimens. PMID- 22669119 TI - Pharmacokinetic characteristics of vincristine sulfate liposomes in patients with advanced solid tumors. AB - AIM: To evaluate the single- and multiple-dose pharmacokinetics of vincristine sulfate liposomes (VSLI) in patients with advanced solid tumors. METHODS: In single-dose pharmacokinetic study, 16 patients were administered VSLI (1.5, 2.0, or 2.3 mg.m(-2)) through intravenous infusion. Another 6 patients receiving vincristine sulfate (VCR, 2.0 mg) were taken as the control. In multiple-dose pharmacokinetic study, 12 patients were administered VSLI (1.5 or 1.8 mg.m(-2)) through intravenous infusion weekly for 4 consecutive weeks. The plasma concentration of VSLI was determined using the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. RESULTS: After intravenous infusion of the single dose of VSLI, the plasma concentrations were characterized by bi-exponential decline curves. No statistically significant differences were observed between the main pharmacokinetic parameters in the 3 dose groups. Compared with the patients receiving VCR, the patients treated with VSLI displayed an increase in the area under the plasma concentration vs time curve (AUC), and a decrease in plasma clearance rates. On the 4th cycle in the multiple-dose study, the plasma concentration of VCR in all subjects prior to the weekly administration was below the lower limit of quantification (LLOQ). The calculated pharmacokinetic parameters from the subjects in the multiple- and single-dose (1.5 mg.m(-2)) groups had no significant differences. Although the administration of liposomal VCR may significantly elevate the plasma concentration of VCR, VSLI-associated adverse events were similar to those associated with conventional VCR. CONCLUSION: VSLI exhibits a lower clearance and a higher AUC compared with conventional VCR. No accumulation was observed in patients exposed to VSLI for 4 consecutive weeks. VSLI was generally tolerated in the subjects. The phase II dose of VSLI may be recommended as 4 doses of 1.5 mg.m(-2) for treatment of patients with advanced solid tumors. PMID- 22669120 TI - Acute and persistent infection by a transfected Mo7 strain of Babesia bovis. AB - A Mo7-derived Babesia bovis line stably transfected with the gfp-bsd gene was inoculated into two four to five months old calves, while two additional calves were inoculated with Mo7 parasites. Similar mild clinical signs were detected in all calves. B. bovis rap-1 was identified in the bloodstream by PCR four days post inoculation (dpi), and consistently over ten months thereafter. Transfusion of blood from experimentally infected calves into four naive splenectomized calves at 212 dpi resulted in acute disease in recipients, confirming persistent infection in the four donor animals. The proportion of GFP expressing parasites recovered from a splenectomized recipient calf is undistinguishable from transfected parasites that were maintained in long term culture under blasticidin selection. Furthermore, the sequences of transfected genes in recovered parasites remained unaltered. Together, the data demonstrates that exogenous B. bovis transgenes can be expressed and remain stable throughout acute and persistent infection in calves. PMID- 22669121 TI - Marshaling leadership for high-value health care: an Institute of Medicine discussion paper. PMID- 22669122 TI - Mitochondria, oxidative stress and neurodegeneration. AB - Mitochondria are involved in ATP supply to cells through oxidative phosphorylation (OXPHOS), synthesis of key molecules and response to oxidative stress, as well as in apoptosis. They contain many redox enzymes and naturally occurring inefficiencies of oxidative phosphorylation generate reactive oxygen species (ROS). CNS functions depend heavily on efficient mitochondrial function, since brain tissue has a high energy demand. Mutations in mitochondrial DNA (mtDNA), generation and presence of ROS and environmental factors may contribute to energy failure and lead to neurodegenerative diseases. Many rare metabolic disorders have been associated with mitochondrial dysfunction. More than 300 pathogenic mtDNA mutations involve proteins that regulate OXPHOS and mitochondrial structural integrity, and have also been described in neurodegenerative diseases with autosomal inheritance. Mitochondria may have an important role in ageing-related neurodegenerative disorders like Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS). In primary mitochondrial and neurodegenerative disorders, there is strong evidence that mitochondrial dysfunction occurs early and has a primary role in pathogenesis. In the present review, we discuss several mitochondrial diseases as models of neurodegeneration. PMID- 22669123 TI - A study of the standard brain in Japanese children: morphological comparison with the MNI template. AB - Functional magnetic resonance imaging (MRI) studies involve normalization so that the brains of different subjects can be described using the same coordinate system. However, standard brain templates, including the Montreal Neurological Institute (MNI) template that is most frequently used at present, were created based on the brains of Western adults. Because morphological characteristics of the brain differ by race and ethnicity and between adults and children, errors are likely to occur when data from the brains of non-Western individuals are processed using these templates. Therefore, this study was conducted to collect basic data for the creation of a Japanese pediatric standard brain. Participants in this study were 45 healthy children (contributing 65 brain images) between the ages of 6 and 9 years, who had nothing notable in their perinatal and other histories and neurological findings, had normal physical findings and cognitive function, exhibited no behavioral abnormalities, and provided analyzable MR images. 3D-T1-weighted images were obtained using a 1.5-T MRI device, and images from each child were adjusted to the reference image by affine transformation using SPM8. The lengths were measured and compared with those of the MNI template. The Western adult standard brain and the Japanese pediatric standard brain obtained in this study differed greatly in size, particularly along the anteroposterior diameter and in height, suggesting that the correction rates are high, and that errors are likely to occur in the normalization of pediatric brain images. We propose that the use of the Japanese pediatric standard brain created in this study will improve the accuracy of identification of brain regions in functional brain imaging studies involving children. PMID- 22669124 TI - One-step conjugation chemistry of DNA with highly scattered silver nanoparticles for sandwich detection of DNA. AB - DNA-silver nanoparticle (AgNP) conjugates were facilely prepared through a one step method, and then used for the quantitative detection of HIV DNA with a sandwich strategy based on their strong plasmon resonance scattering signals. PMID- 22669125 TI - [Indications and outcome of ventilated patients treated in a neurological intensive care unit]. AB - OBJECTIVE: This study characterized artificially ventilated patients in a neurological intensive care unit (NICU) between 2006-2008 in a purely neurological clinic and a so-called stand-alone situation. In addition the long term prognoses as well as the quality of life of surviving patients were investigated. METHODS: All ventilated patients from October 2006 to December 2008 were enrolled in this descriptive, retrospective study. The duration of stay in intensive care was analyzed and the current quality of life was prospectively assessed based on the patient records. Final diagnoses, duration of intensive care unit and ventilation as well as the highest score in SAPS II (simplified acute physiology score) and complications during hospitalization were determined. The patients were divided into groups based on the diagnoses as vascular, inflammatory, neurodegenerative, hereditary, epileptogenic and others. Additionally patients were contacted and asked to respond by completing questionnaires on the Barthel index (BI) and the modified Rankin scale (mRS). RESULTS: During the study period a total of 512 patients were treated in the NICU of whom 201 required artificial respiration. Cerebrovascular diseases were the main reason for therapy in the NICU in 96 out of 201 cases (47.8%), followed by inflammatory diseases in 46 (22.8%) and epileptogenic diseases in 26 patients (13%). The median duration of artificial respiration was 9 days with a mean treatment duration of 16 days (range 1-57 days). Of the patients 31 (15.4%) died in the NICU and an additional 32 patients (18.8%) died within a median of 2 months after discharge. Outcome data were available from 67 out of 170 sent questionnaires and rehabilitation reports of 86 patients, which enabled the outcome of 121 surviving patients to be analyzed (71.2%). Of these 42.2% showed no or mild impairment in everyday life. However, the remaining 38% had severe impairments according to the BI. The evaluation of the mRS showed that 49.6% of the patients still had severe symptoms. CONCLUSIONS: More than one third of the patients treated in the NICU required artificial ventilation with an emphasis on cerebrovascular diseases, which illustrates the overlap between stroke unit and NICU care. Despite a lengthy duration of ventilation and a long stay in the intensive care unit more than one third of surviving patients showed no or only mild impairment. However, an additional third suffered from severe disability up to nursing care dependency. The study data differ little from the few publications in this field despite the stand alone situation of the NICU. The case mix index per day averaged around 0.3 and underlines the economic importance with respect to other forms of neurological treatment. PMID- 22669126 TI - [Diagnosis of dopa-responsive dystonia after 34 years: complete remission after L dopa treatment]. PMID- 22669129 TI - Mapping of reinforcing and analgesic effects of the mu opioid agonist endomorphin 1 in the ventral midbrain of the rat. AB - INTRODUCTION: Agonists at the mu opioid receptor (MOR) are widely recognized for their effects on reward and pain. Although prior studies have attributed some of these effects to MORs on GABA neurons in the ventral tegmental area (VTA), recent studies have identified a region of particularly strong MOR immunostaining residing caudal to the VTA, in a region denoted the rostromedial tegmental nucleus (RMTg). METHODS: Hence, we examined whether rats would self-administer small doses (50-250 pmol) of the selective MOR agonist endomorphin-1 (EM1) into the RMTg and adjacent sites. EM1 was chosen due to its short half-life, thus limiting drug spread, and due to its presence endogenously in brain neurons, including some afferents to the RMTg. RESULTS: The highest rates of EM1 self administration occurred within 0.5 mm of the RMTg center, in a region roughly 0.8 1.6 mm caudal to the majority of VTA DA neurons. In contrast, self-administration rates were much lower in the adjacent VTA, interpeduncular nucleus, central linear nucleus, or median raphe nucleus. Furthermore, EM1 infusions into the RMTg, but not surrounding regions, produced conditioned place preference, while EM1 infusions into the RMTg but not anterior VTA markedly reduced formalin induced pain behaviors. EM1 effects were mimicked by infusions of the GABA agonist muscimol into the same region, consistent with EM1 having inhibitory actions on its target neurons. CONCLUSION: These results implicate a novel brain region in modulating MOR influences on both appetitive and aversive behavior. PMID- 22669132 TI - KRAS-LCS6 genotype as a prognostic marker in early-stage CRC--letter. PMID- 22669131 TI - Best practices in cancer nanotechnology: perspective from NCI nanotechnology alliance. AB - Historically, treatment of patients with cancer using chemotherapeutic agents has been associated with debilitating and systemic toxicities, poor bioavailability, and unfavorable pharmacokinetics. Nanotechnology-based drug delivery systems, on the other hand, can specifically target cancer cells while avoiding their healthy neighbors, avoid rapid clearance from the body, and be administered without toxic solvents. They hold immense potential in addressing all of these issues, which has hampered further development of chemotherapeutics. Furthermore, such drug delivery systems will lead to cancer therapeutic modalities that are not only less toxic to the patient but also significantly more efficacious. In addition to established therapeutic modes of action, nanomaterials are opening up entirely new modalities of cancer therapy, such as photodynamic and hyperthermia treatments. Furthermore, nanoparticle carriers are also capable of addressing several drug delivery problems that could not be effectively solved in the past and include overcoming formulation issues, multidrug-resistance phenomenon, and penetrating cellular barriers that may limit device accessibility to intended targets, such as the blood-brain barrier. The challenges in optimizing design of nanoparticles tailored to specific tumor indications still remain; however, it is clear that nanoscale devices carry a significant promise toward new ways of diagnosing and treating cancer. This review focuses on future prospects of using nanotechnology in cancer applications and discusses practices and methodologies used in the development and translation of nanotechnology-based therapeutics. PMID- 22669133 TI - Plaque sealing and passivation with a mechanical self-expanding low outward force nitinol vShield device for the treatment of IVUS and OCT-derived thin cap fibroatheromas (TCFAs) in native coronary arteries: report of the pilot study vShield Evaluated at Cardiac hospital in Rotterdam for Investigation and Treatment of TCFA (SECRITT). AB - AIMS: The aim of the pilot SECRITT trial was to evaluate the safety and feasibility of sealing the high risk IVUS and optical coherence tomography derived thin cap fibroatheroma (TCFA), with a dedicated nitinol self-expanding vShield device. METHODS AND RESULTS: After screening with angiography, fractional flow reserve (FFR), intravascular ultrasound virtual histology (IVUS-VH) and optical coherence tomography (OCT), 23 patients met enrolment criteria (presence of non-obstructive VH-derived TCFA lesion with thin cap on OCT) and were randomised to vShield (n=13) versus medical therapy (n=10). In the shielded group, baseline percent diameter stenosis was 33.2+/-13.5%, FFR was 0.93+/-0.06. At six-month follow-up in shielded patients percent diameter stenosis further decreased to 18.7+/-16.9% and FFR remained the same 0.93+/-0.05. Average late loss was 0.24+/-0.13 mm. Average baseline fibrous cap thickness was 48+/-12 um. After shield placement at six-month follow-up neo-cap formation was observed with average cap thickness of 201+/-168 um. There were no dissections after shield placement and no plaque ruptures. In addition, mean stent area of 8.76+/-2.16 mm2 increased to 9.45+/-2.30 mm2, that is by 9% at six-month follow-up. The number of malapposed struts decreased from 10.7% to 7.6% and the number of uncovered struts at six months was 8.1%. There were no device-related major adverse cardiovascular events (MACE) events at six-month follow-up. CONCLUSIONS: High risk plaque passivation and sealing with a vShield self-expanding nitinol device appears feasible and safe. A long-term larger randomised study with streamlined screening criteria is needed to evaluate the efficacy of this approach over medical therapy. PMID- 22669134 TI - Diaphragmatic breathing exercises and pelvic floor retraining in children with dysfunctional voiding. AB - BACKGROUND: Dysfunctional voiding (DV) in neurologically normal children is characterized by involuntary intermittent contractions of either the striated muscle in external urethral sphincter, or the pelvic floor during voiding. Urinary incontinence, pelvic holding maneuvers, voiding difficulties, urinary tract infections (UTIs), constipation and vesicoureteral reflux are highly associated with DV. AIM: To investigate the role of abdominal and pelvic floor muscle (PFM) retraining in children with DV. DESIGN: Prospective clinical controlled study SETTING: Outpatient clinical facility POPULATION: Forty-three children, 5-13 years of age, with dysfunctional voiding METHODS: In addition to standard urotherapy (education, timed voiding, adequate fluid intake, voiding posture and pattern, constipation management and hygiene issues), children were assigned abdominal and PFM retraining. Diaphragmatic breathing exercises were done in lying and sitting positions, for the purpose of achieving abdominal muscle relaxation. PFM retraining consisted of low-level three-second contractions followed by thirty-second relaxation periods. Selected children received pharmacotherapy (anticholinergics or desmopressin). Recurrent symptomatic UTIs were treated with antibiotic prophylaxis. Uroflowmetry with PFM electromyography and ultrasound residual urine volumes were obtained before and at the end of the 12-month treatment period. Clinical manifestations and uroflowmetry parameters were analysed before and after the therapy. RESULTS: After one year of therapy, urinary incontinence was cured in 20 out of 24 patients (83%), nocturnal enuresis in 12 out of 19 children (63%), while 13 out of 19 children (68%) were UTI free. All 15 patients recovered from constipation. Post-treatment uroflowmetry parameters showed significant improvements and a bell shaped curve was observed in 36 out of 43 children. CONCLUSION: In combination with standard urotherapy, abdominal and pelvic floor muscle retraining is beneficial for curing urinary incontinence, nocturnal enuresis and UTIs in children with DV, as well as for normalizing urinary function. Further trials are needed to define the most effective treatment program which would result in the best treatment outcome. CLINICAL REHABILITATION IMPACT: To improve clinical and objective treatment outcome in dysfunctional voiders. Diaphragmatic breathing and pelvic floor muscle exercises are simple and easy to learn and could be assigned to children aged 5 or older. As they do not require special equipment, they can be performed at all health care levels. PMID- 22669135 TI - Relation between maximum phonation time and exercise capacity in chronic heart failure patients. AB - BACKGROUND: Patients with chronic heart failure (CHF) commonly fatigue easily due to low peak oxygen uptake (peak VO(2)), an important index of exercise capacity. Maximum phonation time (MPT) is widely used to evaluate maximum vocal capabilities because it is non-invasive, quick, and inexpensive. AIM: The aim of this study was to determine the relation between MPT and exercise capacity, and MPT required to attain an exercise capacity of >=5 metabolic equivalents (METs) in CHF outpatients. DESIGN: Cross-sectional study. SETTING: Outpatient cardiac rehabilitation unit. POPULATION: We enrolled 111 CHF outpatients (mean age 54.2+/ 10.1 years). METHODS: Peak VO(2) was assessed during cardiopulmonary exercise testing (CPX) as the index of exercise capacity. After CPX, we divided the patients into two groups according to exercise capacity: >=5 METs group (N.=68) and <5 METs group (N.=43). Measurements of MPT were taken in the seated position. All patients were asked to produce a sustained vowel /a:/ for as long as possible and were verbally encouraged during respiratory effort. RESULTS: After adjustment for patient clinical characteristics, MPT in the CHF patients was found to be significantly higher in the >=5 METs group than in the <5 METs group (22.1+/-8.4 vs. 17.0+/-11.6 s, F=13.5, P<0.001). Receiver-operating characteristic curve analysis of exercise capacity of >=5 METs extracted a cutoff value for MPT of 18.27 s, with a sensitivity of 0.76, 1-specificity of 0.33, and AUC value of 0.81 (95% CI: 0.70-0.87, P<0.001). CONCLUSION: There were differences in MPT in relation to an exercise capacity threshold of >=5 METs in CHF outpatients. A MPT of 18.27 sec may be the best cutoff value to identify people with or without exercise capacity of >=5 METs. CLINICAL REHABILITATION IMPACT: Measurement of MPT may be a useful method for estimating exercise capacity in CHF outpatients. PMID- 22669136 TI - Electrochemical sensing based on printable temporary transfer tattoos. AB - The realization of epidermal chemical sensing requires a fabrication methodology compatible with the non-planarity and irregularities of the human anatomy. This communication describes the development of printed temporary transfer tattoo (T3) electrochemical sensors for physiological and security monitoring of chemical constituents leading to the demonstration of 'electronic skin'. PMID- 22669139 TI - Introduction for the Special Issue on Glycosylation and Immunity. PMID- 22669140 TI - "Strength in numbers". PMID- 22669141 TI - Clinicopathologic conference: multiquadrant expansile fibro-osseous lesion in a juvenile. AB - This paper intends to present clinical, radiologic, and histopathologic features of a case of gigantiform cementoma manifesting in a 14-year-old boy, without any familial involvement. He has been followed for 3 years. Further cases from the literature have been reviewed that confirm a similar clinicopathologic picture. This is the first case report that describes "non-familial gigantiform cementoma" after the World Health Organisation's classification of 2005. PMID- 22669143 TI - Effect of an herbal compound for treatment of burning mouth syndrome: randomized, controlled, double-blind clinical trial. AB - OBJECTIVE: This randomized, double-blind, placebo-controlled clinical study aimed at evaluating the effect of the systemic use of an herbal compound (Catuama) on the symptoms of burning mouth syndrome (BMS). STUDY DESIGN: Seventy-two patients with BMS were randomly allocated into test (n = 38) and control (n = 34) groups. Patients were instructed to take 2 capsules each day for 8 weeks. They were reassessed at 4, 8, and 12 weeks after treatment onset using a faces scale (FS) and a visual numeric scale (VNS). RESULTS: Although both groups demonstrated a reduction in symptoms, the improvement observed in the test group was significantly greater than in the control group after 4 (FS: P = .010) and 8 (VNS: P = .03; FS: P < .001) weeks of treatment. This significant reduction was maintained 12 weeks after treatment onset (FS, VNS: P = .001). CONCLUSIONS: The systemic administration of Catuama reduces the symptoms of BMS and may be a novel therapeutic strategy for the treatment of this disease. PMID- 22669142 TI - Increased risk of mortality and loss to follow-up among HIV-positive patients with oropharyngeal candidiasis and malnutrition before antiretroviral therapy initiation: a retrospective analysis from a large urban cohort in Johannesburg, South Africa. AB - OBJECTIVE: We investigated the effect of oropharyngeal candidiasis (OC) and body mass index (BMI) before antiretroviral therapy (ART) initiation on treatment outcomes of human immunodeficiency virus (HIV)-positive patients. STUDY DESIGN: Treatment outcomes included failure to increase CD4 count by >=50 or >=100 cells/MUL or failure to suppress viral load (<400 copies/mL) at 6 or 12 months in addition to loss to follow-up (LTFU) and mortality by 12 months. Risk and hazard ratios (HRs) were estimated with the use of log-binomial regression and Cox proportional hazards models, respectively. RESULTS: Baseline CD4 <100 cells/MUL, low BMI (<18.5 kg/m(2)), low hemoglobin, and elevated aspartate transaminase were associated with OC at ART initiation. Patients with low BMI with and without, respectively, OC were at risk of mortality (HR 2.42, 95% CI 1.88-3.12; HR 1.87, 95% CI 1.54-2.28) and LTFU (HR 1.36, 95% CI 1.02-1.82; HR 1.55, 95% CI 1.30 1.85). CONCLUSIONS: Low BMI (with/without OC) at ART initiation was associated with poor treatment outcomes. Conversely, normal BMI with OC was associated with adequate CD4 response and reduced LTFU compared with without OC. PMID- 22669144 TI - Differential collagenolytic activity of Candida albicans isolated from oral mucosa and dentinal carious lesions of HIV-infected children. AB - OBJECTIVE: The aim of this study was to compare type I collagen degradation by Candida albicans isolated from oral mucosa (M) and cavitated active dentinal caries (CAD) of HIV-infected children. STUDY DESIGN: To verify the proteolytic activity, the specimens were cultivated in brain-heart infusion medium and the supernatants were incubated in the presence or absence of type I collagen at 37 degrees C for 12 hours and analyzed using 10% sodium dodecyl sulfate polyacrylamide gel electrophoresis. Intensity of the bands on the gels was assessed by densitometric analysis using a scanner and images analyzed with software from Kodak Digital Science EDAS 120. RESULTS: Supernatants of all the C. albicans degraded type I collagen: that from M, on average, by 38.3% (SD 21.67) and that from CAD by 54% (SD 25.94; Wilcoxon test: P < .05). Predisposing factors had no association with the percentage of type I collagen degradation (Mann Whitney test: P > .05). CONCLUSIONS: Candida albicans from different sites of the oral cavity of HIV-infected children has proteolytic activity for type I collagen. PMID- 22669145 TI - A comparative study of microvessel density in squamous cell carcinoma of the oral cavity and lip. AB - OBJECTIVES: The objective of this study was to comparatively evaluate the density of lymphatic vessels (LVD) and neoformed microvessels (NMVD) in squamous cell carcinoma of the oral cavity (OCSCC) and lip (LSCC). Association between LVD/NMVD and vascular endothelial growth factor (VEGF)-A/-C was also assessed. STUDY DESIGN: OCSCC and LSCC were compared with regard to immunoexpression of LVD, NMVD, and vascular endothelial growth factor-A (VEGF)-A/-C. Association between VEGF-A/-C with vascularity was also assessed. Statistical analyses were performed using t test, Pearson chi(2), and Mann-Whitney tests. Statistical significance was accepted at P less than .05. RESULTS: The NMVD and VEGF-C expressions were significantly higher in OCSCC compared with LSCC. NMVD was associated with VEGF-C in OCSCC, but not in LSCC. CONCLUSIONS: Differences in NMVD and VEGF-C were found between OCSCC and LSCC. Positive association between VEGF-C and NMVD was observed in OCSCC, but not in LSCC, which may be one of the contributing factors that account for the distinctive clinical-biological behavior of these lesions. PMID- 22669146 TI - Tetraploidy with double t(11;18) of recurrent MALT lymphoma in buccal mucosa: a case report. AB - Mucosa-associated lymphoid tissue (MALT) lymphoma is a type of an extranodal marginal zone B-cell lymphoma that accounts for about 5% to 8% of all B-cell lymphomas. It is rare for a recurrent oral MALT lymphoma to have tetraploidy with a double t(11;18) chromosomal abnormality, however. A 66-year-old Japanese woman with a swelling of the right buccal mucosa was referred to our hospital. A tumor was excised, and a pathologic diagnosis of MALT lymphoma with a t(11;18) (q21; q21) chromosome translocation was made. Two years later, swelling of the right buccal mucosa recurred, which was then excised and pathologically diagnosed as MALT lymphoma. This tumor did not have a t(11;18) (q21; q21) chromosome translocation, but exhibited tetraploidy with double t(11;18). FISH analysis revealed that the recurrent MALT lymphoma of the buccal mucosa had tetraploidy with double t(11;18). This is the first reported case of a recurrent MALT lymphoma showing tetraploidy with double t(11;18). PMID- 22669147 TI - Calcifying cystic odontogenic tumor associated with other lesions: case report with cone-beam computed tomography findings. AB - The calcifying cystic odontogenic tumor (CCOT) simultaneously occurring with other lesions at different locations in the same patient is rare. We report a patient with CCOT associated with an odontoma, a supernumerary tooth, and a dentigerous cyst simultaneously occurring in the maxilla. Cone-beam computed tomography (CBCT) images showed a well-defined expansile lesion with internal calcification, high-density masses surrounded by low-density area, and a supernumerary tooth at the anterior maxilla. Posterolaterally to these lesions, an embedded canine with pericoronal radiolucency was detected. Histopathologic examination revealed a CCOT associated with an odontoma, a supernumerary tooth, and a dentigerous cyst of the embedded canine. Enucleation was performed, and a 2 year postoperative follow-up was uneventful. CBCT was useful in giving the differential diagnosis by depicting internal calcification of CCOT, and in revealing the extent and complex relationship of these lesions. PMID- 22669148 TI - Comment on surgical management of solitary venous malformation in the midcheek region. PMID- 22669150 TI - Should pain be used as predictor of prognosis in oral squamous cell carcinomas? PMID- 22669152 TI - Lingual nerve deficit following mandibular third molar removal: review of the literature and medicolegal considerations. AB - The removal of mandibular third molars is probably the most frequently performed procedure in oral and maxillofacial surgery, and it is the most common surgical procedure associated with lingual nerve deficit. Lingual sensory impairment remains a clinical problem in oral and maxillofacial surgery and has serious medical and legal implications. In fact, damage to the lingual nerve is a common cause of litigation in dentistry. The purpose of this article was to review the literature about lingual nerve deficit following mandibular third molar removal and discuss the associated medicolegal aspects. PMID- 22669153 TI - A new approach for atraumatic implant explantation and immediate implant installation. AB - OBJECTIVE: This study reports a new approach for implant extraction in a convenient, fast, and atraumatic way and allowing a new implant placement at same surgical time. STUDY DESIGN: The Biotechnology Institute extraction kit consists of a wrench that allows a 200 N-cm countertorque force, an internal connection extractor, an extractor for external connection, and a set of ratchet handle extension pieces. In this study, a total of 91 implants installed in 42 patients were explanted. RESULTS: Extraction torques ranged from 80 to 200 N-cm. In those cases in which implant removal torques exceeded 200 N-cm, a 2-3-mm depth incision was done using a set of atraumatic trephines to avoid too high countertorque forces. CONCLUSIONS: The possibility of extracting osseointegrated implants opens new doors in oral implantology. The extraction kit allows dentists to re-treat cases and improve the final results, achieving the best outcomes for patients. PMID- 22669154 TI - Recombinant human nerve growth factor (rhNGF-beta) gene transfer promotes regeneration of crush-injured mental nerve in rats. AB - OBJECTIVE: The aim of this study was to evaluate whether the recombinant human nerve growth factor (rhNGF-beta) gene transfer at a crush-injured sensory nerve can enhance nerve regeneration. STUDY DESIGN: A 4-mm crush injury was made on the mental nerve of mandible in rats, and rhNGF-beta adenovirus (6 MUL, concentration = 1.0 * 10(11) pfu/MUL) was injected at the crushed site for the experimental group (NGF-Ad group, n = 15) and the same volume of PBS for the controls (PBS group, n = 15). A sham group of uninjured nerve was also used for the normal control (Sham group, n = 15). The effect of rhNGF-beta adenovirus injection was evaluated by real-time reverse trascriptase polymerase chain reaction for the quantification of nerve growth factor (NGF), low-affinity NGF receptor (p75NTR), and its tyrosine receptor kinase A (trkA) mRNA expression at the trigeminal ganglion (TG) 5 days after injection. Nerve regeneration was evaluated with sensory test, retrograde axonal transport in the TG, and histomorphometric study for 4 weeks. RESULTS: NGF, p75NTR, and trkA mRNA expression was significantly increased at the TG 5 days after injection of rhNGF-beta adenovirus (P < .05). The NGF-Ad group showed improved sensory recovery (P < .05), and the number of retrograde-labeled sensory neurons and soma size of TG were larger compared with the PBS groups (P < .05). Histomorphometrically, the myelinated axon number, myelin thickness, and G-ratio in the NGF-Ad group was also significantly higher than the PBS groups (P < .05). CONCLUSIONS: Recombinant human nerve growth factor gene transfer promoted regeneration of crush-injured mental nerve. PMID- 22669155 TI - Clinical study of the relationship between implant stability measurements using Periotest and Osstell mentor and bone quality assessment. AB - OBJECTIVES: The purpose of this study was to evaluate the relationship between subjective bone quality assessments and objective implant stability values using Periotest and Osstell Mentor, which are widely used clinically, to assess the correlation between these 2 measurements. STUDY DESIGN: A total of 211 dental implants (114 in the maxilla and 97 in the mandible) were placed in 162 patients (89 males and 73 females). Bone quality type was classified according to the Lekholm and Zarb classification. After implant placement, implant stability was measured using Periotest and Osstell Mentor. Implant stability was represented by the implant stability quotient (ISQ) values and periotest values (PTVs). All of the procedures were performed by 1 operator to reduce potential errors. RESULTS: The ISQ values were higher in the mandible (72.77 +/- 8.77) than in the maxilla (65.72 +/- 8.65), whereas PTVs were lower in the mandible (-3.02 +/- 2.63) than in the maxilla (-0.17 +/- 2.82). A statistically significant correlation was found between bone quality type and both ISQ values and PTVs. A significant negative correlation was found between the ISQ values and PTVs (P < .01). CONCLUSION: Both measurements seem to be useful in predicting implant placement prognosis and in determining loading protocols. PMID- 22669156 TI - Osteochondroma of the temporomandibular joint: report of 2 cases emphasizing the importance of personalizing the surgical treatment. AB - BACKGROUND: Osteochondromas (OCs) are rare in the craneofacial area (0.6%). We present 2 cases of OC of the mandibular condyle, emphasizing the surgical decision of each case. CASE 1: In a 48-year-old woman with facial asymmetry, left cross-bite, and mandible deviation to the left, a computerized tomographic (CT) scan confirmed the presence of a bony expansion of the right condyle. The clinical diagnosis was osteochondroma. The patient underwent condylectomy with costochondral reconstruction. CASE 2: In a 76-year-old woman with a 1-month history of right preauricular pain, CT showed a deformed right condyle with a bony mass at the base of the temporal bone and the articular fossa. OC of the skull base was diagnosed, with possibly a concurrent lesion of the condyle. The patient underwent condylectomy with the removal of the skull base mass and an inmediate TMJ reconstruction by means of an appropriately sized stock total TMJ prosthesis. CONCLUSIONS: It is necessary to personalize the temporomandibular joint reconstructive options. PMID- 22669157 TI - Effect of thin nano-hydroxyapatite coating on implant osseointegration in ovariectomized rats. AB - PURPOSE: The purpose of this study was to investigate the effect of the thin nano hydroxyapatite (nano-HA) coating on implant osseointegration in an ovariectomized rat model. MATERIALS AND METHODS: Implants were divided into a control group and a test group (nano-HA-coated group). Surface morphology was examined using field emission scanning electron microscopy (FSEM). Surface roughness of both groups was performed. Sixteen ovariectomized rats randomly received 2 implants in both tibiae. After 12 weeks of implantation, tibias were retrieved and prepared for histomorphometric evaluation and removal torque tests (RTQ). RESULTS: Rodlike crystals uniformly covered the porous surfaces and the surface morphology of the implant was still clear. No significant differences were found in surface roughness between the 2 groups (P > .05). More bone tissue was formed around test implants compared with control implants. Test implants showed a significantly greater BIC, bone area within all threads, and RTQ values compared with control implants (P < .05). CONCLUSIONS: These results indicate the thin nano-HA coating by an electrochemical process has potential benefits to enhance implant osseointegration in ovariectomized rats. PMID- 22669158 TI - New talent: Americas. PMID- 22669159 TI - Clinical relevance of circulating CK-19mRNA-positive tumour cells before front line treatment in patients with metastatic breast cancer. AB - BACKGROUND: To investigate the clinical relevance of CK-19mRNA-positive circulating tumour cells (CTCs) detected before the initiation of front-line treatment in patients with metastatic breast cancer (MBC). METHODS: The presence of CTCs was detected in 298 patients with MBC using a real-time PCR (RT-PCR assay. In 44 patients, the detection of CTCs was evaluated by both the CellSearch and the RT-PCR assay. Interaction with known prognostic factors and association of CTCs with clinical outcome were investigated. RESULTS: There was a strong correlation between the detection of CTCs by both assays. CK-19mRNA-positive CTCs were detected in 201 (67%) patients and their detection was independent of various patients' clinico-pathological characteristics. The median progression free survival (PFS; 9.2 vs 11.9 months (mo), P=0.003) and the overall survival (OS; 29.7 vs 38.9 mo, P=0.016) were significantly shorter in patients with detectable CK-19mRNA-positive CTCs compared with patients without detectable CTCs. Multivariate analysis demonstrated that oestrogen receptor status, performance status and detection of CTCs were emerged as independent prognostic factors associated with decreased PFS and OS. CONCLUSION: The detection of CK 19mRNA-positive CTCs in patients with MBC before front-line therapy could define a subgroup of patients with dismal clinical outcome. PMID- 22669160 TI - FADD protein release mirrors the development and aggressiveness of human non small cell lung cancer. AB - BACKGROUND: The need to unfold the underlying mechanisms of lung cancer aggressiveness, the deadliest cancer in the world, is of prime importance. Because Fas-associated death domain protein (FADD) is the key adaptor molecule transmitting the apoptotic signal delivered by death receptors, we studied the presence and correlation of intra- and extracellular FADD protein with development and aggressiveness of non-small cell lung cancer (NSCLC). METHODS: Fifty NSCLC patients were enrolled in this prospective study. Intracellular FADD was detected in patients' tissue by immunohistochemistry. Tumours and distant non tumoural lung biopsies were cultured through trans-well membrane in order to analyse extracellular FADD. Correlation between different clinical/histological parameters with level/localisation of FADD protein has been investigated. RESULTS: Fas-associated death domain protein could be specifically downregulated in tumoural cells and FADD loss correlated with the presence of extracellular FADD. Indeed, human NSCLC released FADD protein, and tumoural samples released significantly more FADD than non-tumoural (NT) tissue (P=0.000003). The release of FADD by both tumoural and NT tissue increased significantly with the cancer stage, and was correlated with both early and late steps of the metastasis process. CONCLUSION: The release of FADD by human NSCLC could be a new marker of poor prognosis as it correlates positively with both tumour progression and aggressiveness. PMID- 22669163 TI - Osteoblast and osteoclast behavior in zebrafish cultured scales. AB - Fish scale culture can be used as a model to test the effects of several molecules on bone metabolism by histological and biochemical methods, although solid cell biology data about the behavior of the scale cells in culture are needed if such a model is to be employed for pharmacological applications. In the present study, we cultured zebrafish scales at various temperatures and for various times and analyzed the behavior of the bone cells in terms of viability and activity. We demonstrated that the cultured scale cells maintained their usual distribution at 28 degrees C until 72 h, after which time episquamal osteoblasts showed an obvious change in their cell organization followed by an increase in cell death. Osteoclast tartrate-resistant acid phosphatase and osteoblast alkaline phosphatase activities were maintained until 72 h but were reduced at 96 h as a consequence of the massive cell death. This scenario indicates that zebrafish scales cultured until 72 h can be considered as an innovative model of explanted organ culture to assay the ability of chemical compounds to modulate the metabolism of bone cells. PMID- 22669164 TI - Diagnostic challenges of hemihematocolpos and dysmenorrhea in adolescents: obstructed hemivagina, didelphys or bicornuate uterus and renal aplasia is a rare female genital malformation. AB - OBJECTIVES: To develop a clear diagnostic and therapeutic strategy for adolescents presenting with abdominal pain and vaginal tumor caused by congenital female genital anomalies, such as blind hemivagina and uterine anomalies, as the lack of the correct diagnosis of the underlying anatomical genitourinary malformation frequently leads to destructive surgical procedures. METHODS: Retrospective study, study group: patients with double/bicornuate uterus, blind hemivagina and hematocolpos (n = 13), controls: patients with uterine malformation and complete vertical vaginal septum (n = 11), analysis for: menarche, age at onset of symptoms, type of malformation, symptoms leading to admission and diagnostic/surgical techniques applied. RESULTS: Median age at diagnosis study group 19.85 (SD +/- 6.23, range 13-23 years) versus controls 26.09 years (SD +/- 7.44, 16-36 years); predominance of imperforated hemivagina: 69.2 % right-sided versus 30.8 % left-sided septum; renal agenesis ipsilateral to imperforate hemivagina 100 % study group versus 9.1 % controls; 84.6 % previous surgical interventions in the study group, such as partial removal of the septum and re-obliteration, unilateral salpingo-ovarectomy and vaginal drainage of pyometra. We used a single transvaginal surgical procedure, including removal of the obstructed vaginal septum and marsupialization of the blind hemivagina. CONCLUSIONS: A diagnostic and therapeutic algorithm for young women presenting with progressive dysmenorrhea and abdominal pain and/or vaginal tumor reduces destructive interventions. PMID- 22669165 TI - A large retroperitoneal cystic venous malformation mimicking bilateral ovarian cystic tumors. AB - INTRODUCTION: Retroperitoneal cysts are a rare disease. Most retroperitoneal cysts of vascular origin have been reported as hemangiomas. However, according to the recent classification of vascular anomalies accepted by the International Society for Study of Vascular Anomalies (ISSVA), these previously reported retroperitoneal hemangiomas should rather have been classified as vascular malformations. CASE REPORT: A 65-year-old woman visited our hospital complaining of a sense of unexplained abdominal fullness. Magnetic resonance imaging suggested a uterine leiomyoma and bilateral ovarian cystic tumors. However, abdominal surgery revealed normal bilateral ovaries, but huge cystic masses in the retroperitoneum. Postoperative histological diagnosis of the retroperitoneal cysts demonstrated that they were venous malformations. CONCLUSION: This is a rare case in which large cystic retroperitoneal venous malformations were preoperatively diagnosed as ovarian cystic tumors. Retroperitoneal hemangiomas should be renamed as vascular malformations following the ISSVA classification. PMID- 22669166 TI - Influence of delta-opioid receptors in the behavioral effects of nicotine. AB - Multiple studies in animal models and humans suggest that the endogenous opioid system is an important neurobiological substrate for nicotine addictive properties. In this study, we evaluated the participation of delta-opioid receptors in different behavioral responses of nicotine by using delta-opioid receptor knockout mice. Acute nicotine administration induced hypolocomotion and antinociception in wild-type mice, which were similar in knockout animals. The development of tolerance to nicotine-induced antinociception was also similar in both genotypes. In agreement, the expression and functional activity of delta opioid receptors were not modified in the different layers of the spinal cord and brain areas evaluated after chronic nicotine treatment. The somatic manifestation of the nicotine withdrawal syndrome precipitated by mecamylamine was also similar in wild-type and delta-opioid receptor knockout mice. In contrast, nicotine induced a conditioned place preference in wild-type animals that was abolished in knockout mice. Moreover, a lower percentage of acquisition of intravenous nicotine self-administration was observed in mice lacking delta-opioid receptors as well as in wild-type mice treated with the selective delta-opioid receptor antagonist naltrindole. Accordingly, in-vivo microdialysis studies revealed that the enhancement in dopamine extracellular levels induced by nicotine in the nucleus accumbens was reduced in mutant mice. In summary, the present results show that delta-opioid receptors are involved in the modulation of nicotine rewarding effects. However, this opioid receptor does not participate either in several acute effects of nicotine or in the development of tolerance and physical dependence induced by chronic nicotine administration. PMID- 22669167 TI - Low doses of 17beta-estradiol rapidly improve learning and increase hippocampal dendritic spines. AB - While a great deal of research has been performed on the long-term genomic actions of estrogens, their rapid effects and implications for learning and memory are less well characterized. The often conflicting results of estrogenic effects on learning and memory may be due to complex and little understood interactions between genomic and rapid effects. Here, we investigated the effects of low, physiologically relevant, doses of 17beta-estradiol on three different learning paradigms that assess social and non-social aspects of recognition memory and spatial memory, during a transcription independent period of memory maintenance. Ovariectomized female CD1 mice were subcutaneously administered vehicle, 1.5 MUg/kg, 2 MUg/kg, or 3 MUg/kg of 17beta-estradiol 15 minutes before social recognition, object recognition, or object placement learning. These paradigms were designed to allow the testing of learning effects within 40 min of hormone administration. In addition, using a different set of ovariectomized mice, we examined the rapid effects of 1.5 MUg/kg, 2 MUg/kg, or 3 MUg/kg of 17beta-estradiol on CA1 hippocampal dendritic spines. All 17beta-estradiol doses tested impacted learning, memory, and CA1 hippocampal spines. 17beta-Estradiol improved both social and object recognition, and may facilitate object placement learning and memory. In addition, 17beta-estradiol increased dendritic spine density in the stratum radiatum subregion of the CA1 hippocampus, but did not affect dendritic spines in the lacunosum-moleculare, within 40 min of administration. These results demonstrate that the rapid actions of 17beta estradiol have important implications for general learning and memory processes that are not specific for a particular type of learning paradigm. These effects may be mediated by the rapid formation of new dendritic spines in the hippocampus. PMID- 22669161 TI - Association of PHB 1630 C>T and MTHFR 677 C>T polymorphisms with breast and ovarian cancer risk in BRCA1/2 mutation carriers: results from a multicenter study. AB - BACKGROUND: The variable penetrance of breast cancer in BRCA1/2 mutation carriers suggests that other genetic or environmental factors modify breast cancer risk. Two genes of special interest are prohibitin (PHB) and methylene-tetrahydrofolate reductase (MTHFR), both of which are important either directly or indirectly in maintaining genomic integrity. METHODS: To evaluate the potential role of genetic variants within PHB and MTHFR in breast and ovarian cancer risk, 4102 BRCA1 and 2093 BRCA2 mutation carriers, and 6211 BRCA1 and 2902 BRCA2 carriers from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2 (CIMBA) were genotyped for the PHB 1630 C>T (rs6917) polymorphism and the MTHFR 677 C>T (rs1801133) polymorphism, respectively. RESULTS: There was no evidence of association between the PHB 1630 C>T and MTHFR 677 C>T polymorphisms with either disease for BRCA1 or BRCA2 mutation carriers when breast and ovarian cancer associations were evaluated separately. Analysis that evaluated associations for breast and ovarian cancer simultaneously showed some evidence that BRCA1 mutation carriers who had the rare homozygote genotype (TT) of the PHB 1630 C>T polymorphism were at increased risk of both breast and ovarian cancer (HR 1.50, 95%CI 1.10-2.04 and HR 2.16, 95%CI 1.24-3.76, respectively). However, there was no evidence of association under a multiplicative model for the effect of each minor allele. CONCLUSION: The PHB 1630TT genotype may modify breast and ovarian cancer risks in BRCA1 mutation carriers. This association need to be evaluated in larger series of BRCA1 mutation carriers. PMID- 22669168 TI - General principals of miRNA biogenesis and regulation in the brain. AB - MicroRNAs (miRNAs) are small, noncoding RNAs that mediate posttranscriptional gene suppression in a sequence-specific manner. The ability of a single miRNA species to target multiple messenger RNAs (mRNAs) makes miRNAs exceptionally important regulators of various cellular functions. The regulatory capacity of miRNAs is increased further by the miRNA ability to suppress gene expression using multiple mechanisms that range from translational inhibition to mRNA degradation. The high miRNA diversity multiplied by the large number of individual miRNA targets generates a vast regulatory RNA network than enables flexible control of mRNA expression. The gene-regulatory capacity and diversity of miRNAs is particularly valuable in the brain, where functional specialization of neurons and persistent flow of information requires constant neuronal adaptation to environmental cues. In this review we will summarize the current knowledge about miRNA biogenesis and miRNA expression regulation with a focus on the role of miRNAs in the mammalian nervous system. PMID- 22669169 TI - Galantamine, an acetylcholinesterase inhibitor and positive allosteric modulator of nicotinic acetylcholine receptors, attenuates nicotine taking and seeking in rats. AB - Current smoking cessation pharmacotherapies have limited efficacy in preventing relapse and maintaining abstinence during withdrawal. Galantamine is an acetylcholinesterase inhibitor that also acts as a positive allosteric modulator of nicotinic acetylcholine receptors. Galantamine has recently been shown to reverse nicotine withdrawal-induced cognitive impairments in mice, which suggests that galantamine may function to prevent relapse in human smokers. However, there are no studies examining whether galantamine administration modulates nicotine self-administration and/or reinstatement of nicotine seeking in rodents. The present experiments were designed to determine the effects of galantamine administration on nicotine taking and reinstatement of nicotine-seeking behavior, an animal model of relapse. Moreover, the effects of galantamine on sucrose maintained responding and sucrose seeking were also examined to determine whether galantamine's effects generalized to other reinforced behaviors. An inverted U shaped dose-response curve was obtained when animals self-administered different unit doses of nicotine with the highest responding for 0.03 mg/kg per infusion of nicotine. Acute galantamine administration (5.0 mg/kg, i.p.) attenuated nicotine self-administration when animals were maintained on either a fixed-ratio 5 (FR5) or progressive ratio (PR) schedule of reinforcement. Galantamine administration also attenuated the reinstatement of nicotine-seeking behavior. No significant effects of galantamine on sucrose self-administration or sucrose reinstatement were noted. Acetylcholinesterase inhibitors have also been shown to produce nausea and vomiting in humans. However, at doses required to attenuate nicotine self-administration, no effects of galantamine on nausea/malaise as measured by pica were noted. These results indicate that increased extracellular acetylcholine levels and/or nicotinic acetylcholine receptor stimulation is sufficient to attenuate nicotine taking and seeking in rats and that these effects are reinforcer selective and not due to adverse malaise symptoms such as nausea. PMID- 22669170 TI - Severe cross-modal object recognition deficits in rats treated sub-chronically with NMDA receptor antagonists are reversed by systemic nicotine: implications for abnormal multisensory integration in schizophrenia. AB - Schizophrenia is a complex and debilitating disorder, characterized by positive, negative, and cognitive symptoms. Among the cognitive deficits observed in patients with schizophrenia, recent work has indicated abnormalities in multisensory integration, a process that is important for the formation of comprehensive environmental percepts and for the appropriate guidance of behavior. Very little is known about the neural bases of such multisensory integration deficits, partly because of the lack of viable behavioral tasks to assess this process in animal models. In this study, we used our recently developed rodent cross-modal object recognition (CMOR) task to investigate multisensory integration functions in rats treated sub-chronically with one of two N-methyl-D-aspartate receptor (NMDAR) antagonists, MK-801, or ketamine; such treatment is known to produce schizophrenia-like symptoms. Rats treated with the NMDAR antagonists were impaired on the standard spontaneous object recognition (SOR) task, unimodal (tactile or visual only) versions of SOR, and the CMOR task with intermediate to long retention delays between acquisition and testing phases, but they displayed a selective CMOR task deficit when mnemonic demand was minimized. This selective impairment in multisensory information processing was dose-dependently reversed by acute systemic administration of nicotine. These findings suggest that persistent NMDAR hypofunction may contribute to the multisensory integration deficits observed in patients with schizophrenia and highlight the valuable potential of the CMOR task to facilitate further systematic investigation of the neural bases of, and potential treatments for, this hitherto overlooked aspect of cognitive dysfunction in schizophrenia. PMID- 22669171 TI - A randomized, double-blind, placebo-controlled, trial of lamotrigine therapy in bipolar disorder, depressed or mixed phase and cocaine dependence. AB - Bipolar disorder is associated with very high rates of substance dependence. Cocaine use is particularly common. However, limited data are available on the treatment of this population. A 10-week, randomized, double-blind, placebo controlled trial of lamotrigine was conducted in 120 outpatients with bipolar disorder, depressed or mixed mood state, and cocaine dependence. Other substance use was not exclusionary. Cocaine use was quantified weekly by urine drug screens and participant report using the timeline follow-back method. Mood was assessed with the Hamilton rating scale for depression, quick inventory of depressive symptomatology self-report, and young mania rating scale. Cocaine craving was assessed with the cocaine-craving questionnaire. Data were analyzed using a random regression analysis that used all available data from participants with at least one postbaseline assessment (n=112). Lamotrigine and placebo groups were similar demographically (age 45.1+/-7.3 vs 43.5+/-10.0 years, 41.8% vs 38.6% women). Urine drug screens (primary outcome measure) and mood symptoms were not significantly different between groups. However, dollars spent on cocaine showed a significant initial (baseline to week 1, p=0.01) and by-week (weeks 1-10, p=0.05) decrease in dollars spent on cocaine, favoring lamotrigine. Few positive trials of medications for cocaine use, other than stimulant replacement, have been reported, and none have been reported for bipolar disorder. Reduction in amount of cocaine use by self-report with lamotrigine suggests that a standard treatment for bipolar disorder may reduce cocaine use. A study limitation was weekly assessment of urine drug screens that decreased the ability to detect between-group differences. PMID- 22669174 TI - Dispersal of deep-sea larvae from the intra-American seas: simulations of trajectories using ocean models. AB - Using data on ocean circulation with a Lagrangian larval transport model, we modeled the potential dispersal distances for seven species of bathyal invertebrates whose durations of larval life have been estimated from laboratory rearing, MOCNESS plankton sampling, spawning times, and recruitment. Species associated with methane seeps in the Gulf of Mexico and/or Barbados included the bivalve "Bathymodiolus" childressi, the gastropod Bathynerita naticoidea, the siboglinid polychaete tube worm Lamellibrachia luymesi, and the asteroid Sclerasterias tanneri. Non-seep species included the echinoids Cidaris blakei and Stylocidaris lineata from sedimented slopes in the Bahamas and the wood-dwelling sipunculan Phascolosoma turnerae, found in Barbados, the Bahamas, and the Gulf of Mexico. Durations of the planktonic larval stages ranged from 3 weeks in lecithotrophic tubeworms to more than 2 years in planktotrophic starfish. Planktotrophic sipunculan larvae from the northern Gulf of Mexico were capable of reaching the mid-Atlantic off Newfoundland, a distance of more than 3000 km, during a 7- to 14-month drifting period, but the proportion retained in the Gulf of Mexico varied significantly among years. Larvae drifting in the upper water column often had longer median dispersal distances than larvae drifting for the same amount of time below the permanent thermocline, although the shapes of the distance-frequency curves varied with depth only in the species with the longest larval trajectories. Even species drifting for >2 years did not cross the ocean in the North Atlantic Drift. PMID- 22669173 TI - Associations between cannabinoid receptor-1 (CNR1) variation and hippocampus and amygdala volumes in heavy cannabis users. AB - Heavy cannabis users display smaller amygdalae and hippocampi than controls, and genetic variation accounts for a large proportion of variance in liability to cannabis dependence (CD). A single nucleotide polymorphism in the cannabis receptor-1 gene (CNR1), rs2023239, has been associated with CD diagnosis and intermediate phenotypes, including abstinence-induced withdrawal, cue-elicited craving, and parahippocampal activation to cannabis cues. This study compared hippocampal and amygdalar volumes (potential CD intermediate phenotypes) between heavy cannabis users and healthy controls, and analyzed interactions between group, rs2023239 variation, and the volumes of these structures. Ninety-four heavy cannabis users participated, of whom 37 (14 men, 23 women; mean age=27.8) were matched to 37 healthy controls (14 men, 23 women; mean age=27.3) for case control analyses. Controlling for total intracranial volume and other confounding variables, matched cannabis users had smaller bilateral hippocampi (left, p=0.002; right, p=0.001) and left amygdalae (p=0.01) than controls. When genotype was considered in the case-control analyses, there was a group by genotype interaction, such that the rs2023239 G allele predicted lower volume of bilateral hippocampi among cannabis users relative to controls (both p<0.001). This interaction persisted when all 94 cannabis users were compared to controls. There were no group by genotype interactions on amygdalar volume. These data replicate previous findings of reduced hippocampal and amygdalar volume among heavy cannabis users, and suggest that CNR1 rs2023239 variation may predispose smaller hippocampal volume after heavy cannabis use. This association should be tested in future studies of brain volume differences in CD. PMID- 22669172 TI - The role of histone acetylation in memory formation and cognitive impairments. AB - Long-term memory formation requires transcription and protein synthesis. Over the past few decades, a great amount of knowledge has been gained regarding the molecular players that regulate the transcriptional program linked to memory consolidation. Epigenetic mechanisms have been shown to be essential for the regulation of neuronal gene expression, and histone acetylation has been one of the most studied and best characterized. In this review, we summarize the lines of evidence that have shown the relevance of histone acetylation in memory in both physiological and pathological conditions. Great advances have been made in identifying the writers and erasers of histone acetylation marks during learning. However, the identities of the upstream regulators and downstream targets that mediate the effect of changes in histone acetylation during memory consolidation remain restricted to a handful of molecules. We outline a general model by which corepressors and coactivators regulate histone acetylation during memory storage and discuss how the recent advances in high-throughput sequencing have the potential to radically change our understanding of how epigenetic control operates in the brain. PMID- 22669175 TI - Thermal biology of sea snakes and sea kraits. AB - Temperature probably had no direct effect on the evolution of sea kraits within their center of origin, a geologically stable thermal zone straddling the equator, but may have indirectly affected expansions and contractions in distributions beyond that zone through global fluctuations that caused alternation of higher and lower sea levels. The northern limit of the Laticauda colubrina complex seems to be the 20 degrees C isotherm; in the south, the range does not reach that isotherm because there is no land (also a habitat requirement of sea kraits) within the zone of suitable temperature. The relationship of temperature to the pattern of geographic variation in morphology supports either the hypothesis of peripheral convergence or the developmental hypothesis but does not distinguish between them. Quadratic surfaces relating cumulative scores for coloration and morphological characters to global position showed a strong latitudinal component and an even stronger longitudinal one in which the direction of the latitudinal effect was reversed between east and west. A multivariate analysis revealed that while morphological characters vary significantly by location and climate when tested separately, when the influence of location on morphology is taken into account, no residual relationship between climate and morphology remains. Most marine snakes have mean upper temperature tolerances between 39 degrees C and 40 degrees C and operate at temperatures much nearer their upper thermal limits than their lower limits but still avoid deleterious extremes by diving from excessively hot water to deeper, cooler strata, and by surfacing when water is cold. At the surface in still water in sunlight, Pelamis can maintain its body temperature slightly above that of the water, but whether this is significant in nature is questionable. As temperature falls below 18-20 degrees C, survival time is progressively reduced, accompanied by the successive occurrence of cessation of feeding, cessation of swimming, and failure to orient. Acclimation does not seem to be in this species' repertoire. In the water column, marine snakes track water temperature; on land, sea kraits can thermoregulate by basking, selecting favorable locations, and by kleptothermy. Laticauda colubrina adjusts its reproductive cycle geographically in ways that avoid breeding in the coldest months. Mean voluntary diving time is not temperature-dependent within the normal range of temperatures experienced by marine snakes in the field, but is reduced in water colder than 20 degrees C. On land, much as while diving in the sea, sea kraits maintain long periods of apnea; intervals between breaths are inversely related to temperature. PMID- 22669176 TI - Water-dispersible and biodegradable polymer micelles with good antibacterial efficacy. AB - New amphiphilic ABC triblock copolymers have been designed and self-assembled into water-dispersible and biodegradable polymer micelles, which exhibit good antibacterial activities without quaternary ammonium moieties or the loading of any external antibiotics due to the increased local concentration of cationic charge in the polymer micelles compared to the un-self-assembled individual polymer chains. PMID- 22669177 TI - Effects of low-level laser therapy (LLLT) on bone repair in rats: optical densitometry analysis. AB - The aim of this study was to evaluate the process of bone repair in rats submitted to low-level laser therapy using optical densitometry. A total of 45 rats which underwent femoral osteotomy were randomly distributed into three groups: control (group I) and laser-treated groups using wavelengths in the red (lambda, 660-690 nm) and in the infrared (lambda, 790-830 nm) spectra (group II and group III, respectively). The animals (five per group) were killed after 7, 14, and 21 days and the femurs were removed for optical densitometry analysis. Optical density showed a significant increase in the degree of mineralization (gray level) in both groups treated with the laser after 7 days. After 14 days, only the group treated with laser therapy in the infrared spectrum showed higher bone density. No differences were observed between groups after 21 days. Such results suggest the positive effect of low-level laser therapy in bone repair is time- and wavelength-dependent. In addition, our results have confirmed that optical densitometry technique can measure bone mineralization status. PMID- 22669178 TI - A high-throughput comparative characterization of laser-induced soft tissue damage using 3D digital microscopy. AB - 3D digital microscopy was used to develop a rapid alternative approach to quantify the effects of specific laser parameters on soft tissue ablation and charring in vitro without the use of conventional tissue processing techniques. Two diode lasers operating at 810 and 980 nm wavelengths were used to ablate three tissue types (bovine liver, turkey breast, and bovine muscle) at varying laser power (0.3, 1.0, and 2.0 W) and velocities (1-50 mm/s). Spectrophotometric analyses were performed on each tissue to determine tissue-specific absorption coefficients and were considered in creating wavelength-dependent energy attenuation models to evaluate minimum heat of tissue ablations. 3D surface contour profiles characterizing tissue damage revealed that ablation depth and tissue charring increased with laser power and decreased with lateral velocity independent of wavelength and tissue type. While bovine liver ablation and charring were statistically higher at 810 than 980 nm (p < 0.05), turkey breast and bovine muscle ablated and charred more at 980 than 810 nm (p < 0.05). Spectrophotometric analysis revealed that bovine liver tissue had a greater tissue-specific absorption coefficient at 810 than 980 nm, while turkey breast and bovine muscle had a larger absorption coefficient at 980 nm (p < 0.05). This rapid 3D microscopic analysis of robot-driven laser ablation yielded highly reproducible data that supported well-defined trends related to laser-tissue interactions and enabled high throughput characterization of many laser-tissue permutations. Since 3D microscopy quantifies entire lesions without altering the tissue specimens, conventional and immunohistologic techniques can be used, if desired, to further interrogate specific sections of the digitized lesions. PMID- 22669180 TI - New iron(III) nitrate hydrates: Fe(NO3)3.xH2O with x = 4, 5 and 6. AB - Crystals of the title compounds were grown from their hydrous melts or solutions. The crystal structure of iron(III) trinitrate hexahydrate {hexaaquairon(III) trinitrate, [Fe(H(2)O)(6)](NO(3))(3)} is built up from [Fe(H(2)O)(6)](2+) octahedra and nitrate anions connected via hydrogen bonds. In iron(III) trinitrate pentahydrate {pentaaquanitratoiron(III) dinitrate, [Fe(NO(3))(H(2)O)(5)](NO(3))(2)}, one water molecule in the coordination octahedron of the Fe(III) atom is substituted by an O atom of a nitrate group. Iron(III) trinitrate tetrahydrate {triaquadinitratoiron(III) nitrate monohydrate, [Fe(NO(3))(2)(H(2)O)(3)]NO(3).H(2)O} represents the first example of a simple iron(III) nitrate with pentagonal-bipyramidal coordination geometry, where two bidentate nitrate anions and one water molecule form a pentagonal plane. PMID- 22669179 TI - Estrogen suppresses heptatic IkappaB expression during short-term alcohol exposure. AB - OBJECTIVE: To assess the effects of sex steroids on hepatic inflammatory pathways in short-term chronically ethanol-fed rats. METHODS: Ovariectomized female Wistar rats (8-12 weeks old, n = 8 per treatment group) were implanted with osmotic pumps releasing 17beta-estradiol (20 MUg/24 h) or testosterone (25 MUg/24 h) and fed liquid diets with or without ethanol (8 % w/v) for two weeks. Hepatic expression of IkappaBalpha/beta, TNF-alpha, and IL-6 mRNA was examined by real time PCR. Liver (nuclear) NFkappaB, IkappaBalpha and beta, IL-6, and IL-6Ralpha protein expression was examined by enzyme-linked immunosorbent assay (ELISA) or Western blot. RESULTS: Estrogen alone induced greater steatosis, NFkappaB translocation, TNF-alpha mRNA, as well as IL-6, and IL-6R protein. Alcohol consumption along with estrogen treatment further increased steatosis, NFkappaB translocation, TNF-alpha mRNA, and IL-6 protein. Conversely, neither estrogen nor ethanol consumption induced IkappaBalpha or IkappaBbeta mRNA or protein expression, while testosterone robustly induced these inhibitory proteins regardless of treatment. CONCLUSIONS: Estrogen exposure enhances alcohol-induced liver inflammation, and the anti-inflammatory effects of testosterone in the liver might be related to induction of IkappaB. Elevated inflammation in response to estrogen may overwhelm the regenerative influence of IL-6 in liver, leading to increased steatosis and greater liver damage. PMID- 22669181 TI - Li3Al(MoO4)3, a lyonsite molybdate. AB - Trilithium aluminium trimolybdate(VI), Li(3)Al(MoO(4))(3), has been grown as single crystals from alpha-Al(2)O(3) and MoO(3) in an Li(2)MoO(4) flux at 998 K. This compound is an example of the well known lyonsite structure type, the general formula of which can be written as A(16)B(12)O(48). Because this structure can accomodate cationic mixing as well as cationic vacancies, a wide range of chemical compositions can adopt this structure type. This has led to instances in the literature where membership in the lyonsite family has been overlooked when assigning the structure type to novel compounds. In the title compound, there are two octahedral sites with substitutional disorder between Li(+) and Al(3+), as well as a trigonal prismatic site fully occupied by Li(+). The (Li,Al)O(6) octahedra and LiO(6) trigonal prisms are linked to form hexagonal tunnels along the [100] axis. These polyhedra are connected by isolated MoO(4) tetrahedra. Infinite chains of face-sharing (Li,Al)O(6) octahedra extend through the centers of the tunnels. A mixed Li/Al site, an Li, an Mo, and two O atoms are located on mirror planes. PMID- 22669182 TI - Lanthanum tetrazinc, LaZn4. AB - The structure of lanthanum tetrazinc, LaZn(4), has been determined from single crystal X-ray diffraction data for the first time, approximately 70 years after its discovery. The compound exhibits a new structure type in the space group Cmcm, with one La atom and two Zn atoms occupying sites with m2m symmetry, and one Zn atom occupying a site with 2.. symmetry. The structure is closely related to the BaAl(4), La(3)Al(11), BaNi(2)Si(2) and CaCu(5) structure types, which can be presented as close-packed arrangements of 18-vertex clusters, in this case LaZn(18). The kindred structure types contain related 18-vertex clusters around atoms of the rare earth or alkaline earth metal. PMID- 22669183 TI - meso-Bis{eta(5)-1-[1-(dimethylamino)ethenyl]-3 (trimethylsilyl)cyclopentadienyl}iron(II) and the cobalt(II) analogue. AB - The two title crystalline compounds, viz. meso-bis{eta(5)-1-[1 (dimethylamino)ethenyl]-3-(trimethylsilyl)cyclopentadienyl}iron(II), [Fe(C(12)H(20)NSi)(2)], (II), and meso-bis{eta(5)-1-[1-(dimethylamino)ethenyl]-3 (trimethylsilyl)cyclopentadienyl}cobalt(II), [Co(C(12)H(20)NSi)(2)], (III), were obtained by the reaction of lithium 1-[1-(dimethylamino)ethenyl]-3 (trimethylsilyl)cyclopentadienide with FeCl(2) and CoCl(2), respectively. For (II), the trimethylsilyl- and dimethylaminoethenyl-substituted cyclopentadienyl (Cp) rings present a nearly eclipsed conformation, and the two pairs of trimethylsilyl and dimethylaminoethenyl substituents on the Cp rings are arranged in an interlocked fashion. In the case of (III), the same substituted Cp rings are perfectly staggered leading to a crystallographically centrosymmetric molecular structure, and the two trimethylsilyl and two dimethylaminoethenyl substituents are oriented in opposite directions, respectively, with the trimethylsilyl group of one Cp ring and the dimethylaminoethenyl group of the other Cp ring arranged more closely than in (II). PMID- 22669184 TI - Methanol[1-(methoxymethanimidoyl)-2-(pyridin-2 ylmethyl)guanidine]bis(perchlorato)copper(II). AB - The title complex, [Cu(ClO(4))(2)(C(9)H(13)N(5)O)(CH(3)OH)], was synthesized from a methanolysis reaction of N-(methylpyridin-2-yl)cyanoguanidine (L(3)) and copper(II) perchlorate hexahydrate in a 1:1 molar ratio. The Cu(II) ion is six coordinated by an N(3)O(3) donor set which confers a highly distorted and asymmetric octahedral geometry. Three N-donor atoms from the chelating 1 (methoxymethanimidoyl)-2-(pyridin-2-ylmethyl)guanidine (L(3m)) ligand and one O atom from the methanol molecule define the equatorial plane, with two perchlorate O atoms in the apical sites, one of which has a long Cu-O bond of 2.9074 (19) A. The dihedral angle between the five- and six-membered chelate rings is 8.21 (8) degrees . Two molecules are associated into a dimeric unit by intermolecular N H...O(perchlorate) hydrogen bonds. Additionally, the weakly coordinated perchlorate anions also link adjacent [Cu(ClO(4))(2)(L(3m))(CH(3)OH)] dimers by hydrogen-bonding interactions, resulting in a two-dimensional layer in the (100) plane. Further C-H...O hydrogen bonds link the two-dimensional layers along [100] to generate a three-dimensional network. PMID- 22669185 TI - One-dimensional coordination polymers generated from a new triazole bridging ligand and HgX2 (X = Cl, Br and I): characterization and luminescent properties. AB - The new 4-amino-1,2,4-triazole asymmetric bridging ligand 4-amino-5-(pyridin-3 yl)-3-[4-(pyridin-4-yl)phenyl]-4H-1,2,4-triazole (L) has been used to generate three novel isomorphic one-dimensional coordination polymers, viz. catena poly[[tris[dichloridomercury(II)]-bis{MU(3)-4-amino-5-(pyridin-3-yl)-3-[4 (pyridin-4-yl)phenyl]-4H-1,2,4-triazole}] acetonitrile monosolvate], {[Hg(3)Cl(6)(C(18)H(14)N(6))(2)].CH(3)CN}(n), (I), and the bromido, {[Hg(3)Br(6)(C(18)H(14)N(6))(2)].CH(3)CN}(n), (II), and iodido, {[Hg(3)I(6)(C(18)H(14)N(6))(2)].CH(3)CN}(n), (III), analogs. The asymmetric ligand acts as a tridentate ligand to coordinate the three different Hg(II) centers (two of which are symmetry-related). Two ligands and two symmetry-related Hg(II) centers form centrosymmetric rectangular units which are linked into one dimensional chains via the other unique Hg atoms, which sit on mirror planes. The chains are elaborated into a three-dimensional structure via interchain hydrogen bonds. The acetonitrile solvent molecules are located in ellipsoidal cavities. The luminescent character of these three coordination complexes was investigated in the solid state. PMID- 22669186 TI - 3,5-Bis{4-[(benzimidazol-1-yl)methyl]phenyl}-4H-1,2,4-triazol-4-amine and its one dimensional polymeric complex with HgCl2. AB - The molecule of 3,5-bis{4-[(benzimidazol-1-yl)methyl]phenyl}-4H-1,2,4-triazol-4 amine (L), C(30)H(24)N(8), has an antiperiplanar conformation of the two terminal benzimidazole groups and forms two-dimensional networks along the crystallographic b axis via two types of intermolecular hydrogen bonds. However, in catena-poly[[[dichloridomercury(II)]-MU-3,5-bis{4-[(benzimidazol-1 yl)methyl]phenyl}-4H-1,2,4-triazol-4-amine] dichloromethane hemisolvate], {[HgCl(2)(C(30)H(24)N(8))].0.5CH(2)Cl(2)}(n), synthesized by the combination of L with HgCl(2), the L ligand adopts a synperiplanar conformation. The Hg(II) cation lies in a distorted tetrahedral environment, which is defined by two N atoms and two Cl atoms to form a one-dimensional zigzag chain. These zigzag chains stack via hydrogen bonds which expand the dimensionality of the structure from one to two. PMID- 22669187 TI - The structures of three Hg2X4L2 macrocycles {X = Cl, Br and I, and L = 1,2-bis[4 (pyridin-3-yl)phenoxy]ethane} assembled from ether-bridged dipyridyl ligands. AB - The new ether-bridged dipyridyl ligand 1,2-bis[4-(pyridin-3-yl)phenoxy]ethane (L) has been used to synthesize three isostructural centrosymmetric binuclear Hg(II) macrocycles, namely bis{MU-1,2-bis[4-(pyridin-3-yl)phenoxy]ethane kappa(2)N:N'}bis[dichloridomercury(II)], [Hg(2)Cl(4)(C(24)H(20)N(2)O(2))(2)], and the bromido, [Hg(2)Br(4)(C(24)H(20)N(2)O(2))(2)], and iodido, [Hg(2)I(4)(C(24)H(20)N(2)O(2))(2)], analogues. The Hg atoms adopt a highly distorted tetrahedral coordination environment consisting of two halides and two pyridine N-donor atoms from two bridging ligands. In the solid state, the macrocycles form two-dimensional sheets in the bc plane through noncovalent Hg...X and X...X (X = Cl, Br and I) interactions. PMID- 22669188 TI - X-ray and DFT-calculated structures of a vanadyl Schiff base complex: (methanol kappaO)[2-methoxy-6-({2-[(2-oxido-3 methoxybenzylidene)amino]benzyl}iminomethyl)phenolato kappa4O1,N,N,O1']oxidovanadium(IV) monohydrate. AB - The central V(V) atom in the title mononuclear oxovanadium complex, [VO(C(23)H(20)N(2)O(4))(CH(3)OH)].H(2)O, has a distorted octahedral coordination. Two N atoms and two O atoms of the Schiff base define the base of the bipyramid and two O atoms are in the apical positions, one from vanadyl and the second from methanol. Density functional theory (DFT) calculations were performed for the title complex and its ligand to compare their geometry in the solid and gas phases. Additional analyses were made of the changes in the geometry of the ligand during complex formation. The HOMA (harmonic oscillator model of aromaticity) descriptor of pi-electron delocalization was calculated to estimate the aromaticity of the benzene rings in the title complex and its ligand. PMID- 22669189 TI - Bis(1-tert-butyl-1H-imidazole-kappaN3)dichloridocobalt(II). AB - In the crystal structure of the title compound, [CoCl(2)(C(7)H(12)N(2))(2)], molecular units are formed by coordination of the unsubstituted N atoms of two tert-butyl-substituted imidazole molecules and two chloride ligands, which distinguishes the complex from structures of imidazolium-based dications with tetrachloridocobaltate dianions. There are two crystallographically independent molecules in the asymmetric unit, related by a noncrystallographic inversion centre. PMID- 22669190 TI - 1-[5-(4,5-Dimethyl-1,3,2-dioxaborolan-2-yl)thiophen-2-yl]ethanone and 4-(4,4,5,5 tetramethyl-1,3,2-dioxaborolan-2-yl)benzaldehyde. AB - In both title compounds, C(10)H(13)BO(3)S, (I), and C(13)H(17)BO(3), (II), the molecules adopt nearly planar conformations. The crystal packing of (I) consists of a supramolecular two-dimensional network with a herringbone-like topology formed by self assembly of centrosymmetric pairs of molecules linked via dipole dipole interactions. The crystal structure of (II) consists of a supramolecular two-dimensional network built up from centrosymmetric pairs of molecules via pi pi interactions. These pairs of molecules are self-organized in an offset fashion related by a symmetry centre, generating supramolecular ribbons running along the [101] direction. Neighbouring ribbons are stacked via complementary van der Waals and hydrophobic methyl-methyl interactions. PMID- 22669191 TI - Hydrogen bis[tris(4-fluorophenyl)phosphane oxide] triiodide. AB - In the title compound, C(36)H(25)F(6)O(2)P(2)(+).I(3)(-), hydrogen-bonded [{(p FC(6)H(4))(3)PO}(2)H](+) dimers assemble along the crystallographic c axis to form channels that house extended chains of triiodide anions. Although the I-I bond lengths of 2.9452 (14) and 2.9023 (15) A are typical, the inter-ion I...I distance of 3.5774 (10) A is unusually short. A posteriori modelling of nonmerohedral twinning about (100) has been only partially successful, achieving a reduction in the maximum residual electron density from 5.28 to 3.24 e A(-3). The inclusion of two low-occupancy I-atom sites (total 1.7%), which can be interpreted as translational disorder of the triiodide anions along the channels, reduced the maximum residual electron density to 2.03 e A(-3). The minor fractional contribution volume of the nonmerohedral twin domains refined to 0.24 and simultaneous refinement of the inversion twin domains showed the crystal to be a 0.5:0.5 inversion twin. PMID- 22669192 TI - Two closely related, and unexpected, quinolinone derivatives: a three-dimensional hydrogen-bonded framework structure and a hydrogen-bonded molecular ribbon of R(2)(2)(18) and R(4)(4)(24) rings. AB - 1,5-Bis(4-chlorophenyl)-3-(2-oxo-1,2-dihydroquinolin-3-yl)pentane-1,5-dione, (Ia), and 1,5-bis(2-chlorophenyl)-3-(2-oxo-1,2-dihydroquinolin-3-yl)pentane-1,5 dione, (Ib), crystallize as an 84:16 mixture, 0.84C(26)H(19)Cl(2)NO(3).0.16C(26)H(19)Cl(2)NO(3), in the space group I4(1)/a, where the molecules of the two isomers occupy very similar sites in the unit cell. A combination of one N-H...O hydrogen bond and one C-H...O hydrogen bond links the molecules, regardless of isomeric form, into a single three-dimensional framework structure. The molecules of (9RS,10RS)-8,9-bis(4-chlorobenzyl)-10-(2 oxo-1,2-dihydroquinolin-3-yl)-5,6,9,10-tetrahydrophenanthridine, C(36)H(22)Cl(2)N(2)O(4), (II), are linked by two hydrogen bonds, one each of the N-H...O and C-H...O types, into a molecular ribbon in which centrosymmetric rings of R(2)(2)(18) and R(4)(4)(24) types alternate. The hydrogen-bonded ribbons enclose channels, which contain highly disordered solvent molecules. PMID- 22669193 TI - Structural characteristics of dibromoborylated benzene derivatives. AB - The crystal structures of five dibromobenzene derivatives, namely dibromoborylbenzene, C(6)H(5)BBr(2), (I), 1-dibromoboryl-4 (trimethylsilyl)benzene, C(9)H(13)BBr(2)Si, (II), 4-bromo-1 (dibromoboryl)benzene, C(6)H(4)BBr(3), (III), dibromo(dimethylamino)(phenyl)borane, C(8)H(12)BBr(2)N, (IV), and dibromo(dimethylsulfanyl)[4-(trimethylsilyl)phenyl]borane, C(11)H(19)BBr(2)SSi, (V), have been determined. Compounds (I)-(IV) crystallize with one molecule in the asymmetric unit, but the molecule of (V) is located on a crystallographic mirror plane, implying twofold disorder of the central aromatic ring, the S atom and one of the methyl groups bonded to the S atom. In (I), (II) and (III), the B atom is three-coordinated, and in (IV) and (V) it is four-coordinated. The geometric parameters of the -BBr(2) group in these five structures agree well with those of comparable structures retrieved from the Cambridge Structural Database. The C-B and B-Br bond lengths in the molecules with a three-coordinated B atom are significantly shorter than those in the molecules with a four coordinated B atom. In the compounds with a three-coordinated B atom, the -BBr(2) group tends to be coplanar with the aromatic ring to which it is attached. PMID- 22669194 TI - Two androsterone derivatives as inhibitors of androgen biosynthesis. AB - The title compounds, (3R,5S,5'R,8R,9S,10S,13S,14S)-10,13-dimethyl-5'-(2 methylpropyl)tetradecahydro-6'H-spiro[cyclopenta[a]phenanthrene-3,2' [1,4]oxazinane]-6',17(2H)-dione, C(26)H(41)NO(3), (I), and methyl (2R)-2 [(3R,5S,8R,9S,10S,13S,14S)-10,13-dimethyl-2',17-dioxohexadecahydro-3'H spiro[cyclopenta[a]phenanthrene-3,5'-[1,3]oxazolidin-3'-yl]]-4-methylpentanoate, C(28)H(43)NO(5), (II), possess the typical steroid shape (A-D rings), but they differ in their extra E ring. The azalactone E ring in (I) shows a half-chair conformation, while the carbamate E ring of (II) is planar. The orientation of the E-ring substituent is clearly established and allows a rationalization of the biological results obtained with such androsterone derivatives. PMID- 22669195 TI - Aripiprazole salts. II. Aripiprazole perchlorate. AB - The molecular structure of aripiprazole perchlorate (systematic name: 4-(2,3 dichlorophenyl)-1-{4-[(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)oxy]butyl}piperazin 1-ium perchlorate), C(23)H(28)Cl(2)N(3)O(2)(+).ClO(4)(-), does not differ substantially from the recently published structure of aripiprazole nitrate [Freire, Polla & Baggio (2012). Acta Cryst. C68, o170-o173]. Both compounds have almost identical bond distances, bond angles and torsion angles. The two different counter-ions occupy equivalent places in the two structures, giving rise to very similar first-order 'packing motifs'. However, these elemental arrangements interact with each other in different ways in the two structures, leading to two-dimensional arrays with quite different organizations. PMID- 22669196 TI - Two dibenzodiazepinone molecules with dissimilar dimeric associations and apparent different tautomeric forms. AB - In two dibenzodiazepinones, viz. the tricyclic core structure, 5H dibenzo[b,e]diazepin-11(10H)-one, C(13)H(10)N(2)O, and an acylated derivative, 1 (11-hydroxy-5H-dibenzo[b,e]diazepin-5-yl)-2-{4-[3-(1H-imidazol-1 yl)propyl]piperidin-1-yl}ethanone ethanol monosolvate, C(26)H(29)N(5)O(2).C(2)H(5)OH, dimeric association via hydrogen-bond bridging between the cyclic amide entities is evident, but there are considerable differences between the parent compound and the amidated derivative. Highly consistent with reported structures of related tricyclic lactams, two molecules of the nonsubstituted compound are bridged through two N-H...O hydrogen bonds across a crystallographic centre of symmetry and the bond lengths of the cyclic amide entity correspond to the amino-oxo (lactam) tautomeric form. In contrast, the structure of the derivative shows two similar, but crystallographically unique, molecules hydrogen bonded into a dimeric unit exhibiting an approximate (noncrystallographic) C2 axis. The bond lengths of the two derivative cyclic amide groups support their potential presence in the hydroxyimine (lactim) tautomeric forms, with the resulting possibility of intermolecular tautomerism. Likely driving forces for the two extreme configurations are discussed. PMID- 22669198 TI - Ruegeria arenilitoris sp. nov., isolated from the seashore sand around a seaweed farm. AB - A Gram-negative, motile and rod-shaped bacterial strain, G-M8(T), which was isolated from seashore sand around a seaweed farm at Geoje island in South Korea, was characterized taxonomically. It grew optimally at 30-37 degrees C, at pH 7.0 8.0 and in presence of 2 % (w/v) NaCl. A neighbour-joining phylogenetic tree based on 16S rRNA gene sequences revealed that strain G-M8(T) joined the cluster comprising the type strains of Ruegeria atlantica and Ruegeria lacuscaerulensis, showing 97.5 % sequence similarity, by a bootstrap resampling value of 85.8 %. It exhibited 16S rRNA gene sequence similarity values of 95.4-96.7 % to the type strains of the other Ruegeria species. Strain G-M8(T) exhibited the highest gyrB sequence similarity value (88.5 %) to the type strain of R. lacuscaerulensis. Strain G-M8(T) contained Q-10 as the predominant ubiquinone and C(18:1) omega7c as the predominant fatty acid. The polar lipid profile of strain G-M8(T) was similar to that of R. atlantica KCTC 12424(T). The DNA G+C content of strain G M8(T) was 64.6 mol% and its mean DNA-DNA relatedness values with R. atlantica KCTC 12424(T) and R. lacuscaerulensis KCTC 2953(T) were 18 +/- 5.3 and 10 +/- 3.6 %, respectively. Differential phenotypic properties, together with the phylogenetic and genetic distinctiveness, demonstrated that strain G-M8(T) is distinguished from other Ruegeria species. On the basis of the data presented, strain G-M8(T) (=KCTC 23960(T) = CCUG 62412(T)) represents a novel species of the genus Ruegeria, for which the name Ruegeria arenilitoris sp. nov. is proposed. PMID- 22669197 TI - Enhanced leavening properties of baker's yeast overexpressing MAL62 with deletion of MIG1 in lean dough. AB - This study aimed to increase maltose fermentation in industrial baker's yeast to increase its leavening properties. To this end, we overexpressed MAL62 encoding alpha-glucosidase (maltase) and deleted MIG1 encoding a transcriptional repressor that regulates MAL gene expression. Strain overexpressing MAL62 showed 46.3 % higher alpha-glucosidase activity and enhanced leaving activity than the parental strain when tested in glucose-maltose low sugar model liquid dough (LSMLD). Deleting MIG1 was much less effective, but it could further strengthen leavening properties in a strain overexpressing MAL62. The relationship between maltose permease and alpha-glucosidase was further dissected by transforming the two genes. The results indicated that without increasing the maltose permease activity, maltose metabolism could also be enhanced by the increased alpha glucosidase activity. Previous strategies for strain improvement have targeted the enhancement of alpha-glucosidase and maltose permease activities in concert. Our results suggest that increasing alpha-glucosidase activity is sufficient to improve maltose fermentation in lean dough. PMID- 22669199 TI - Kineococcus endophytica sp. nov., a novel endophytic actinomycete isolated from a coastal halophyte in Jiangsu, China. AB - A novel Gram-positive, motile, non-spore-forming coccus-shaped bacterial strain, designated KLBMP 1274(T), was isolated from a halophytic plant (Limonium sinense) collected from the coastal region of Nantong, Jiangsu Province, in east China. Phylogenetic analyses based on the 16S rRNA gene sequence showed that strain KLBMP 1274(T) belongs to the genus Kineococcus and is closely related to Kineococcus rhizosphaerae RP-B16(T) (98.72 %), Kineococcus aurantiacus IFO 15268(T) (98.71 %), Kineococcus radiotolerans SRS30216(T) (98.69 %) and Kineococcus gynurae KKD096(T) (97.33 %). The 16S rRNA gene sequence similarity to other species of the genus Kineococcus was <97 %. The cell wall contained meso diaminopimelic acid as the diagnostic diamino acid, with arabinose and galactose as the characteristic sugars. The predominant menaquinone was MK-9(H(2)). The polar lipids were found to be diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, phosphatidylinositol mannosides, an unknown phospholipid, an unknown glycolipid, and three unknown lipids. Major cellular fatty acids were found to be anteiso-C(15: 0) and iso-C(14: 0). The chemotaxonomic data for strain KLBMP 1274(T) were typical of the genus Kineococcus. The total DNA G+C content was 73.4 mol %. DNA-DNA relatedness and differential phenotypic data demonstrated that strain KLBMP 1274(T) was clearly distinguished from all closely related species of the genus Kineococcus. Thus, strain KLBMP 1274(T) represents a novel species of the genus Kineococcus, for which the name Kineococcus endophytica sp. nov. is proposed. The type strain is KLBMP 1274(T) (=KCTC 19886 (T) = NBRC 108674(T)). PMID- 22669200 TI - Cerebral oedema as a complication following treatment of a giant arachnoid cyst. PMID- 22669201 TI - Motor cortex evaluation by nTMS after surgery of central region tumors: a feasibility study. AB - BACKGROUND: Largely discussed during the past decade, motor cortex reorganization in brain tumor surgery has been investigated only by few studies. We therefore aimed to investigate cortical motor representation after resection of perirolandic WHO grade II and III gliomas using navigated transcranial magnetic stimulation (nTMS). METHODS: Five patients were examined before neurosurgery and after a follow-up period of 17.7 +/- 6.8 months. As a control, five healthy age matched subjects were equally studied by nTMS in two sessions spaced 12.6 (range 2-35) days apart. Resting motor thresholds (RMT), hotspots and centers of gravity (CoG) were identified for the first dorsal interosseous (FDI), abductor pollicis brevis (APB), extensor digitorum (EXT), tibialis anterior (TA) and abductor hallucis (AH) muscles. Euclidian distances, coefficients of variance and intraclass correlation coefficients (ICC) were calculated. RESULTS: Healthy subjects showed moderate to excellent reliability measurement of RMT (ICC = 0.69 0.94). Average displacement of CoGs across sessions was 0.68 +/- 0.34 cm in the dominant and 0.76 +/- 0.38 cm in the non-dominant hemisphere; hotspots moved 0.87 +/- 0.51 cm and 0.83 +/- 0.45 cm, respectively. In one patient these parameters differed significantly from the control group (p < 0.05 for both CoGs and hotspots). Overall, all patients' CoGs moved 1.12 +/- 0.93 cm, and hotspots were 1.06 +/- 0.7 cm apart. In both patients and healthy subjects, movement of assessed parameters was more important along the X- than the Y-axis. CONCLUSIONS: nTMS allows evaluating cortical reorganization after brain tumor surgery. It may contribute to the understanding of neurofunctional dynamics, thus influencing therapeutic strategy. PMID- 22669202 TI - 3D T2-weighted turbo spin-echo MR sequence for identifying cerebrospinal fluid leak after endoscopic endonasal pituitary surgery. AB - BACKGROUND: This study aimed to assess the efficacy of MR images with 3D T2 weighted turbo spin-echo (3D T2-TSE) sequences for early identification of postoperative cerebrospinal fluid (CSF) leaks. METHODS: We analyzed the medical records and radiological reports for 72 consecutive patients who underwent an endoscopic endonasal approach for sellar and parasellar lesions between April 2009 and December 2010. Patients were 38 men and 34 women with a mean age of 46.4 years. All underwent MR scanning within 2 postoperative days, which included 3D T2-TSE sequences as well as a conventional T2-weighted (T2W) protocol. Sequence accuracy in predicting postoperative CSF leaks was assessed for sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). RESULTS: A postoperative CSF leak was confirmed in 6 of 72 patients (8.3 %). On immediate postoperative MR images, 39 patients were suspicious for CSF leaks on conventional T2W sequences, while 18 patients on 3D T2-TSE. The 3D T2-TSE imaging had superior specificity and PPV (50 % vs. 81.8 %, 15.4 % vs. 33.3 %), while there was no difference in sensitivity and NPV compared with conventional T2W sequences. CONCLUSION: Compared to the conventional T2W protocol, MR imaging with the 3D T2-TSE protocol provides differential images around the sellar area with improved specificity and PPV for the detection of postoperative CSF leaks. PMID- 22669203 TI - Highly controlled immortal polymerization of beta-butyrolactone by a dinuclear indium catalyst. AB - An ethoxy-bridged dinuclear indium catalyst was used for the ring opening polymerization of the cyclic ester beta-butyrolactone to form the biodegradable polyester poly(hydroxybutyrate) (PHB). The catalyst shows remarkable activity and control during polymerization, allowing for formation of diblock polymers. Addition of high ratios of alcohols to the catalyst leads to fast chain transfer and immortal polymerization. PMID- 22669204 TI - Finasteride and methadone use and risk of advanced hepatitis C related liver disease. AB - AIM: We evaluated the association between two medications that alter bioavailable androgen levels, finasteride and methadone, and risk of advanced HCV-related liver disease. BACKGROUND: Males have strikingly greater cirrhosis risk across disease etiologies, including hepatitis C virus (HCV) infection. METHODS: In a cross-sectional study in HCV+ male veterans, we determined medication use by up to 15-year medical record review, and hepatic pathology by the FibroSURE-ActiTest (F3/F4-F4, advanced vs. F0-F3, mild fibrosis; and A2/A3-A3, advanced vs. A0-A2, mild inflammation). We performed race-adjusted and race-stratified multivariate analyses. RESULTS: Among 571 HCV+ males, 43 % were White and 57 % African American. There were non-significant decreased risks with finasteride use (OR(adj advanced fibrosis) = 0.75, 95 % CI 0.39-1.45 and OR(adj advanced inflammation) = 0.74, 95 % CI 0.41-1.43). For methadone, there was a non-significant 41 % increased advanced fibrosis risk in Whites and 51 % reduced risk in AA. White male methadone-users had 2.1-fold excess advanced inflammation risk (p = 0.15). CONCLUSIONS: Our preliminary study results suggest finasteride use is not significantly associated with a decreased risk of advanced hepatic fibrosis or inflammation in HCV+ males. The ethnically-divergent results for methadone associated fibrosis risk and finding of potentially increased inflammation risk in White males suggests the need for additional research. PMID- 22669205 TI - Missense mutations in MLH1, MSH2, KRAS, and APC genes in colorectal cancer patients in Malaysia. AB - BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide with approximately 1 million cases diagnosed annually. In Malaysia, CRC is the second most common cancer in women and ranked first in men. The underlying cause of CRC remains unknown. AIMS: The aim of this study was to analyze the mutations in genes involved in CRC including MLH1, MSH2, KRAS, and APC genes. METHODS: A total of 76 patients were recruited. We used the polymerase chain reaction denaturing high-performance liquid chromatography for the detection of mutations in the mismatch repair (MMR) and APC genes and the PCR single-strand conformation polymorphism for screening of the KRAS gene mutations. RESULTS: We identified 17 types of missense mutations in 38 out of 76 patients in our patients. Nine mutations were identified in the APC gene, five mutations were detected in the KRAS gene, and two mutations were identified in the MSH2 gene. Only one mutation was identified in MLH1. Out of these 17 mutations, eight mutations (47 %) were predicted to be pathogenic. Seven patients were identified with multiple mutations (3: MSH2 and KRAS, 1: KRAS and APC, 1: MLH1 and APC, 2: APC and APC). CONCLUSIONS: We have established the PCR-DHPLC and PCR-SSCP for screening of mutations in CRC patients. This study has given a snapshot of the spectrum of mutations in the four genes that were analyzed. Mutation screening in patients and their family members will help in the early detection of CRC and hence will reduce mortality due to CRC. PMID- 22669206 TI - Fatigue: a prevalent symptom in gastroparesis. AB - BACKGROUND: Fatigue is seen in many medical conditions. Patients with gastroparesis may complain of fatigue. AIM: The aim of this work is to first assess the prevalence and severity of fatigue in patients with gastroparesis, and secondly to correlate fatigue with symptoms, quality of life, and factors that may contribute to fatigue. METHODS: One hundred and fifty-six patients with gastroparesis filled out questionnaires including the fatigue assessment instrument (FAI), patient assessment of upper gastrointestinal symptom severity index, patient assessment of upper gastrointestinal disorders-quality of life and hospital anxiety, and depression scale to evaluate for fatigue, symptoms, quality of life, and depression. Gastric emptying test and laboratory studies for hemoglobin, glycosylated hemoglobin, thyroid function (TSH), and inflammatory markers (CRP and ESR) were obtained. RESULTS: Fatigue was reported by 93 % of patients. The mean total FAI score was 3.71 +/- 0.2, with 51 % of patients having a score above 4, indicating severe fatigue. There were moderate correlations between fatigue and many symptoms of gastroparesis: upper abdominal discomfort (r = 0.446), upper abdominal pain (r = 0.422), loss of appetite (r = 0.329), bloating (r = 0.297), and abdominal distention (r = 0.265). Fatigue in patients using metoclopramide (3.5 +/- 0.4) was similar to patients using domperidone (3.7 +/- 0.5) or neither medicine (3.8 +/- 0.3). Fatigue severity correlated with a decreased quality of life (r = -0.694, p < 0.001), increased depression (r = 0.339, p = 0.009), lower anxiety (r = -0.441, p < 0.001), and lower hemoglobin levels (r = -0.258, p = 0.005), but not to glycosylated hemoglobin, ESR, CRP, TSH, or gastric emptying. CONCLUSIONS: Fatigue is an important significant symptom in patients with gastroparesis with a high prevalence and severity. Fatigue is correlated with many symptoms of gastroparesis, low hemoglobin, depression, inflammation, decreased quality of life, but not to severity of delayed gastric emptying or to medication use. PMID- 22669207 TI - Anti-Saccharomyces cerevisiae antibodies associate with phenotypes and higher risk for surgery in Crohn's disease: a meta-analysis. AB - BACKGROUND: Recent studies suggested that anti-Saccharomyces cerevisiae antibody (ASCA) status was associated with diagnostic findings, stratified classification phenotypes, disease activity and clinical course of Crohn's disease (CD). However, the relationship between ASCA status and phenotypes of CD remains controversial in these studies. AIMS: The purpose of this study was to evaluate whether ASCA status is associated with the phenotypes and the risk of surgery in diverse populations in CD. METHODS: We conducted a meta-analysis of studies assessing the association of ASCA status with phenotypes and risk of surgery in CD. Three independent reviewers undertook data extraction. We pooled odds ratios separately for the cohort and case-control studies. RESULTS: We identified ten cohort studies (n = 2,365) and 14 case-control studies (n = 1,887) that investigated the association of ASCA status with phenotypes and risk of surgery in CD. The meta-analysis of the cohort studies showed significant association between the ASCA-positive status and higher risk of early-onset age (OR 2.25, 95 % CI 1.41-3.57, P < 0.001), ileal involvement disease (1.70, 1.05-2.77, P = 0.03), complicated disease behavior (2.09, 1.71-2.57, P < 0.001), perianal disease (1.49, 1.14-1.94, P = 0.004), and risk for surgery (1.61, 1.29-2.01, P < 0.001). Meta-analysis of the case-control studies also showed a significantly higher risk in ileal involvement disease (1.77, 1.25-2.49, P = 0.001), complicated disease behavior (2.13, 1.70-2.68, P < 0.001), perianal disease (1.96, 1.38-2.78, P < 0.001), and risk for surgery (1.71, 1.17-2.49, P = 0.005), except for the early-onset age (1.16, 0.80-1.69, P = 0.44). CONCLUSIONS: This meta-analysis indicated that positive ASCA status is a risk factor for early onset age, ileal involvement, complicated behavior, perianal disease and requirement for surgery in CD. PMID- 22669208 TI - Helicobacter pylori infection increases the risk of colorectal adenomas: cross sectional study and meta-analysis. AB - BACKGROUND: The studies concerning the association between Helicobacter pylori status and colorectal adenoma, premalignant lesions of colorectal cancers, are not consistent. METHODS: This cross-sectional study investigated the association of colorectal adenoma with H. pylori infection in a consecutive series of 2,195 asymptomatic average-risk subjects who underwent screening colonoscopy and H. pylori testing. Multivariate analyses were adjusted for potential relevant confounders, including age, sex, smoking, alcohol consumption, family history of colorectal cancer, and regular use of aspirin. Furthermore, we performed a systematic literature review and meta-analysis of available studies, including the current study, to clarify whether H. pylori infection is associated with an increased risk of colorectal adenoma. RESULTS: Among 2,195 eligible subjects, 1,253 subjects were H. pylori seropositive and 942 subjects were seronegative. In the H. pylori (+) group, the prevalence of colorectal adenoma and advanced adenoma was significantly higher than in the H. pylori (-) group (25.3 vs. 20.1 %, p = 0.004 and 6.1 vs. 2.9 %, p < 0.001, respectively). In our multivariate analysis, H. pylori seropositivity was an independent risk factor for overall colorectal adenoma (OR = 1.36, 95 % CI = 1.10-1.68) and advanced adenoma (OR = 2.21, 95 % CI = 1.41-3.48). The positive association was confined in cases with any proximal adenoma. In the meta-analysis, which included ten studies and 15,863 patients, the pooled OR for colorectal adenoma related to H. pylori infection was 1.58 (95 % CI = 1.32-1.88). CONCLUSION: Our results from this cross-sectional study and current studies included in our meta-analysis indicated that H. pylori infection was associated with a modest increase in the risk for colorectal adenoma. PMID- 22669209 TI - Patients with esophageal motility disorders show distinct patterns based on axial force measurements. AB - BACKGROUND: Using manometry, the classification of motility-related disorders in the esophagus is vague and overlapping. We present a new method, which combines manometry and axial force measurements in a single catheter. AIM: The aim was to examine the manometric and axial force recordings during swallows. METHODS: Recordings from 20 patients suffering from diffuse esophageal spasms (DES) (8), achalasia (5) and other diseases including gastro-oesophageal reflux (7) were compared to recordings made in ten healthy subjects. The probe was capable of measuring axial force 6.5-cm proximal to the lower esophageal sphincter (LES) and pressures 8-, 10- and 12-cm proximal to the LES. After insertion, five dry and five wet swallows were made. Swallows were repeated with 0, 2, 4 and 6 ml of water in a bag mounted distal to the axial force recording site. Each contraction was analysed for duration and amplitude, and was categorised according to its configuration. RESULTS: The number of failed contractions measured with axial force was lower for the achalasia (P < 0.001) and DES groups (P < 0.001) compared to the healthy volunteers. The number of multi-peaked contractions was unchanged for the achalasia and DES groups while it increased for the group of healthy volunteers. On several occasions a negative traction force was encountered though the manometric pattern appeared normal. CONCLUSIONS: Measurements of axial force generated by primary peristalsis provide additional information about esophageal neuromuscular function in different diseases that is not demonstrable with manometry alone. PMID- 22669210 TI - Complexation of high methoxyl pectin with ethanol desolvated whey protein nanoparticles: physico-chemical properties and encapsulation behaviour. AB - Using a desolvation method, whey protein isolate (WPI) nanoparticles were prepared and mixed with high methoxyl pectin (HMP) solutions (DE 72.8) to form WPI-HMP supramolecular complexes at low pH. Aqueous dispersions containing 5% WPI at pH 9 were desolvated with ethanol, and then diluted in HMP solutions at pH 3. Changes in particle size of the HMP-WPI complexes were studied as a function of HMP concentration. Upon dilution of the WPI nanoparticles in 0.05% HMP at pH 3, the average apparent diameter (d(90)) was around 270 nm, and there were no differences with desolvation level. These nanoparticles would undergo coarsening with storage at room temperature. The complexes showed to withstand homogenization and although heating increased aggregation, the particle size of the heated suspensions improved after homogenization. In addition, the suspensions demonstrated higher interfacial pressures (measured by drop tensiometry) compared to the corresponding unprocessed, desolvated or heated WPI solutions, suggesting their employment as surface active ingredients. The encapsulation efficiency of the desolvated WPI suspensions and desolvated WPI-HMP complex suspensions was studied using a model hydrophilic dye. In all cases, appreciable amounts of dye molecule were encapsulated and retained by the nanoparticles during storage at pH 3. PMID- 22669211 TI - The odd fate of a chicken dinner. PMID- 22669212 TI - Central serous chorioretinopathy after blunt trauma. AB - The authors report a case of a 46-year-old Hispanic male with central serous chorioretinopathy (CSC) following blunt trauma to the left eye. The patient presented with a complaint of throbbing headache and blurry vision in left eye. The patient was diagnosed with diabetes mellitus 1 year previous to the event. On examination, uncorrected visual acuity was 20/20 OD, 20/200 OS. No anisocoria or afferent pupillary defect was present. Intraocular pressure was normal. Subconjunctival haemorrhage and lid ecchymosis were present in OS and fundus examination showed serous macular detachment and central retinal pigment epithelium detachment, and no evidence of diabetic retinopathy. Optical coherence tomography OS showed subretinal fluid and fluorescein angiography demonstrated the typical 'smokestack' pattern of leakage into the subretinal space. The patient received observational therapy for 4 months and the CSC spontaneously resolved with visual acuity of 20/20 in left eye. PMID- 22669214 TI - An unusual cause of hoarseness. AB - A 55-year-old man had a 3 month history of hoarseness and choking when he drinks liquids. Physical examination revealed evidence of left sided palsy of 9th, 10th, 11th and 12th cranial nerves. A brain MRI revealed a skull base lytic lesion. The authors diagnosed Collet-Sicard syndrome. The patient was found to have colon cancer. He received palliative skull radiotherapy and died few weeks later in hospice care. PMID- 22669213 TI - Community acquired Pseudomonas pneumonia in an immune competent host. AB - Pseudomonas aeruginosa is an uncommon cause of community-acquired pneumonia in immune-competent hosts. It is commonly seen in patients with structural lung abnormality such as cystic fibrosis or in immune compromised hosts. Here, the authors report a case of community-acquired Pseudomonas pneumonia in a 26-year old healthy man who presented with 8-week history of malaise and cough. PMID- 22669215 TI - Cortical blindness and posterior reversible encephalopathy syndrome in an older patient. AB - Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiological entity. It associates, to varying extents, neurological symptoms such as headaches, confusion, seizures and visual alterations from haemianopsia to cortical blindness. The diagnosis relies on brain MRI, showing signs of subcortical and cortical oedema in the posterior regions of the brain, with hypersignals in T2/fluid attenuated inversion recovery (FLAIR) or diffusion sequences. With early diagnosis and control of the causal factors, the symptoms and radiological signs can be - as the name implies - totally regressive. PRES can be caused by various heterogeneous factors, such as hypertension, side effect of drug therapies, eclampsia, sepsis or autoimmune diseases. The authors report here the case of an 86-year-old woman, presenting totally regressive cortical blindness and seizures, with compatible imaging. PMID- 22669217 TI - Microbiome: Pathogens and commensals fight it out. PMID- 22669216 TI - Is there an association between Vogt-Koyonagi-Harada syndrome and intracranial meningioma? AB - The authors report a case of Vogt-Koyonagi-Harada syndrome associated with intracranial meningioma. The authors discuss the HLA-DR4 gene as a common and causative factor in both conditions. This case report draws attention to the possibility of a causative association between intracranial meningioma and Vogt Koyonagi-Harada syndrome, a rare but potentially blinding condition if not detected and treated early. PMID- 22669218 TI - Bacterial physiology: Another brick in the wall. PMID- 22669221 TI - FRED and HYBRID docking performance on standardized datasets. AB - The docking performance of the FRED and HYBRID programs are evaluated on two standardized datasets from the Docking and Scoring Symposium of the ACS Spring 2011 national meeting. The evaluation includes cognate docking and virtual screening performance. FRED docks 70 % of the structures to within 2 A in the cognate docking test. In the virtual screening test, FRED is found to have a mean AUC of 0.75. The HYBRID program uses a modified version of FRED's algorithm that uses both ligand- and structure-based information to dock molecules, which increases its mean AUC to 0.78. HYBRID can also implicitly account for protein flexibility by making use of multiple crystal structures. Using multiple crystal structures improves HYBRID's performance (mean AUC 0.80) with a negligible increase in docking time (~15 %). PMID- 22669223 TI - Selective total encapsulation of the sulfate anion by neutral nano-jars. AB - Nano-sized toroidal copper(II)-hydroxide/pyrazolate assemblies, lined by H-bond donors on the inside and hydrophobic on the outside, selectively extract sulfate from mixtures with nitrate or perchlorate. Tetrabutylammonium "lids" seal the "nano-jars" and render the encapsulated sulfate anion completely buried and inaccessible, so that it is not precipitated by Ba(2+) ions. PMID- 22669219 TI - The microbiology of asthma. AB - Asthma remains an important human disease that is responsible for substantial worldwide morbidity and mortality. The causes of asthma are multifactorial and include a complex mix of environmental, immunological and host genetic factors. In addition, epidemiological studies show strong associations between asthma and infection with respiratory pathogens, including common respiratory viruses such as rhinoviruses, human respiratory syncytial virus, adenoviruses, coronaviruses and influenza viruses, as well as bacteria (including atypical bacteria) and fungi. In this Review, we describe the many roles of microorganisms in the risk of developing asthma and in the pathogenesis of and protection against the disease, and we discuss the mechanisms by which infections affect the severity and prevalence of asthma. PMID- 22669220 TI - Replication-transcription conflicts in bacteria. AB - DNA replication and transcription use the same template and occur concurrently in bacteria. The lack of temporal and spatial separation of these two processes leads to their conflict, and failure to deal with this conflict can result in genome alterations and reduced fitness. In recent years major advances have been made in understanding how cells avoid conflicts between replication and transcription and how such conflicts are resolved when they do occur. In this Review, we summarize these findings, which shed light on the significance of the problem and on how bacterial cells deal with unwanted encounters between the replication and transcription machineries. PMID- 22669224 TI - Results from a large-scale epidemiologic look-back investigation of improperly reprocessed endoscopy equipment. AB - OBJECTIVE: To determine whether improper high-level disinfection practices during endoscopy procedures resulted in bloodborne viral infection transmission. DESIGN: Retrospective cohort study. SETTING: Four Veterans Affairs medical centers (VAMCs). PATIENTS: Veterans who underwent colonoscopy and laryngoscopy (ear, nose, and throat [ENT]) procedures from 2003 to 2009. METHODS: Patients were identified through electronic health record searches and serotested for human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV). Newly discovered case patients were linked to a potential source with known identical infection, whose procedure occurred no more than 1 day prior to the case patient's procedure. Viral genetic testing was performed for case/proximate pairs to determine relatedness. RESULTS: Of 10,737 veterans who underwent endoscopy at 4 VAMCs, 9,879 patients agreed to viral testing. Of these, 90 patients were newly diagnosed with 1 or more viral bloodborne pathogens (BBPs). There were no case/proximate pairings found for patients with either HIV or HBV; 24 HCV case/proximate pairings were found, of which 7 case patients and 8 proximate patients had sufficient viral load for further genetic testing. Only 2 of these cases, both of whom underwent laryngoscopy, and their 4 proximates agreed to further testing. None of the 4 remaining proximate patients who underwent colonoscopy agreed to further testing. Mean genetic distance between the 2 case patients and 4 proximate patients ranged from 13.5% to 19.1%. CONCLUSIONS: Our investigation revealed that exposure to improperly reprocessed ENT endoscopes did not result in viral transmission in those patients who had viral genetic analysis performed. Any potential transmission of BBPs from colonoscopy remains unknown. PMID- 22669225 TI - Managing and preventing exposure events from inappropriately reprocessed endoscopes. PMID- 22669226 TI - Adequate disinfection of a split-septum needleless intravascular connector with a 5-second alcohol scrub. AB - OBJECTIVE: Define optimum vascular catheter connector valve disinfection practices under laboratory and clinical conditions. DESIGN: Prospective observational clinical survey and laboratory assessment of disinfection procedures. SETTING: All adult inpatients at an academic healthcare center. METHODS: In the clinical setting, contamination of needleless connectors was assessed in 6 weekly prevalence surveys in which the connector valves from central venous catheters (CVCs) in situ were cultured by pressing the connector diaphragm to an agar plate. Before culture, valves were disinfected by scrubbing the diaphragm with a 70% isopropyl alcohol pledget for 0, 5, 10, 15, or 30 seconds. In the laboratory, the diaphragms on 150 unused sterile connector valves were inoculated with 10(3), 10(5), or 10(8) colony-forming units of Staphylococcus epidermidis and allowed to dry. After disinfection of the diaphragms by scrubbing with a 70% isopropyl alcohol pledget for 0, 5, 10, 15, or 30 seconds, the valves were sampled by pressing the diaphragm to an agar plate. RESULTS: In the clinical setting, 363 connector valves from patients with CVCs were sampled, and 66.7% of nondisinfected valves revealed bacterial contamination. After 5-second disinfection with an alcohol pledget, only 1 (1.4%) of 71 yielded microbial growth (P < .005). In the laboratory, at the 10(3) and 10(5) inoculum, all connector valves yielded sterile cultures when scrubbed for 5 or more seconds (P < .001). At the 10(8) inoculum, 2 (20%) of 10 connector valves yielded minimal growth of S. epidermidis. CONCLUSIONS: A 5-second scrub with a 70% isopropyl alcohol pledget yields adequate disinfection of a split-septum intravascular catheter connector valve under clinical and laboratory conditions. PMID- 22669227 TI - Association of Bacillus cereus infection with contaminated alcohol prep pads. AB - BACKGROUND: Bacillus species have caused healthcare-associated outbreaks of invasive disease as well as pseudo-outbreaks. We report an outbreak investigation of blood cultures positive for Bacillus cereus associated with alcohol prep pads (APPs) contaminated with B. cereus and Bacillus species resulting in a rapid internal product recall and subsequent international product recall. DESIGN: Epidemiologic and microbiologic outbreak investigation. SETTING: A 300-bed tertiary care children's hospital in Aurora, Colorado. PATIENTS: Patients with blood or cerebrospinal fluid cultures positive for B. cereus. METHODS: Three patients with blood cultures positive for B. cereus were identified in late 2010. Breaches in procedural and surgical techniques, common interventions, and products were explored. The following 3 common products were cultured: sterile saline syringes, chlorhexidine/alcohol skin preparation solution, and APPs. Repetitive sequence-based polymerase chain reaction (Rep-PCR) was used to compare isolates obtained from patients and from APPs and was confirmed by independent pulsed-field gel electrophoresis. RESULTS: There appeared to be a significant increase in blood cultures positive for B. cereus during 2009-2010. B. cereus and other Bacillus species were cultured from the internal contents of 63.3% of APPs not labeled as sterile, and 8 of the 10 positive lots were manufactured after 2007. None of the isolates obtained from the patients matched strains isolated from the APPs. However, some lots of APPs had strains that were indistinguishable from one another. CONCLUSIONS: APPs that were not labeled as sterile were contaminated with Bacillus species. The product was immediately recalled internally and replaced with APPs from another manufacturer that were labeled as sterile. On January 3, 2011, the manufacturer voluntarily recalled its APPs. Healthcare facilities, healthcare providers, and users of APPs should avoid the use of APPs not specifically labeled as sterile. PMID- 22669228 TI - Positive cultures of organ preservation fluid predict postoperative infections in solid organ transplantation recipients. AB - OBJECTIVE: The significance of positive cultures of organ preservation fluid (OPF) in solid organ transplantation is not known. We sought to describe the microbiology and define the clinical impact of positive OPF cultures. DESIGN: Retrospective cohort study. SETTING: Tertiary care hospital. PATIENTS: A consecutive sample of all solid organ transplantations at our center between July 2006 and January 2009 was reviewed. A total of 331 allografts (185 kidneys, 104 livers, 31 pancreases, and 11 hearts) met the inclusion criterion of having OPF cultures taken from the transplanted allograft. METHODS: Organisms recovered from OPF were classified as high or low risk according to their virulence. Clinical outcomes were compared between recipients of organs with positive OPF cultures and recipients of organs with negative OPF cultures. RESULTS: OPF cultures were positive in 62.2% of allografts and yielded high-risk organisms in 17.8%. Normal skin flora constituted the majority of positive OPF cultures, while Enterobacteriaceae spp. and Staphylococcus aureus made up the majority of high risk organisms. Recipients of allografts with positive OPF cultures developed more frequent bacterial infections, regardless of allograft type (relative risk, 2.39; 95% confidence interval [CI], 1.61-3.54). Moreover, isolation of a given organism in OPF samples was associated with the development of a clinical infection with the same organism, regardless of allograft type. CONCLUSIONS: Positive cultures of OPF are common events in solid organ transplantation, frequently involve high-risk organisms, and are associated with the development of postoperative clinical bacterial infections. Further study is required to determine the optimal strategies for their prevention and management. PMID- 22669229 TI - Cluster randomized trial to evaluate the effect of a multimodal hand hygiene improvement strategy in primary care. AB - OBJECTIVE: To evaluate the effectiveness of a multimodal intervention in primary care health professionals for improved compliance with hand hygiene practice, based on the World Health Organization's 5 Moments for Health Hygiene. DESIGN: Cluster randomized trial, parallel 2-group study (intervention and control). SETTING: Primary healthcare centers in Madrid, Spain. PARTICIPANTS: Eleven healthcare centers with 198 healthcare workers (general practitioners, nurses, pediatricians, auxiliary nurses, midwives, odontostomatologists, and dental hygienists). Methods. The multimodal hand hygiene improvement strategy consisted of training of healthcare workers by teaching sessions, implementation of hydroalcoholic solutions, and installation of reminder posters. The hand hygiene compliance level was evaluated by observation during regular care activities in the office visit setting, at the baseline moment, and 6 months after the intervention, all by a single external observer. RESULTS: The overall baseline compliance level was 8.1% (95% confidence interval [CI], 6.2-10.1), and the healthcare workers of the intervention group increased their hand hygiene compliance level by 21.6% (95% CI, 13.83-28.48) compared with the control group. CONCLUSIONS: This study has demonstrated that hand hygiene compliance in primary healthcare workers can be improved with a multimodal hand hygiene improvement strategy. PMID- 22669230 TI - Monitoring hand hygiene via human observers: how should we be sampling? AB - OBJECTIVE: To explore how hand hygiene observer scheduling influences the number of events and unique individuals observed. DESIGN: We deployed a mobile sensor network to capture detailed movement data for 6 categories of healthcare workers over a 2-week period. SETTING: University of Iowa Hospital and Clinic medical intensive care unit (ICU). METHODS: We recorded 33,721 time-stamped healthcare worker entries to and exits from patient rooms and considered each entry or exit to be an opportunity for hand hygiene. Architectural drawings were used to derive 4 optimal line-of-sight placements for observers. We ran simulations for different observer movement schedules, all with a budget of 1 hour of total observation time. We considered observation times of 1-15, 15-30, 30, and 60 minutes per station. We stochastically generated healthcare worker hand hygiene compliance on the basis of all data and recorded the total unit compliance as it would be reported by each simulated observer. RESULTS: Considering a 60-minute total observation period, aggregate simulated observers captured 1.7% of the average total number of opportunities per day at best and 0.5% at worst. The 1-15 minute schedule captures, on average, 16% fewer events than does the 60-minute (ie, static) schedule, but it samples 17% more unique individuals. The 1-15 minute schedule also provides the best estimator of compliance for the duration of the shift, with a mean standard deviation of 17%, compared with 23% for the 60 minute schedule. CONCLUSIONS: Our results show that observations are sensitive to different observers' schedules and suggest the importance of using data-driven approaches to schedule hand hygiene audits. PMID- 22669231 TI - Findings of the International Nosocomial Infection Control Consortium (INICC), Part I: Effectiveness of a multidimensional infection control approach on catheter-associated urinary tract infection rates in pediatric intensive care units of 6 developing countries. AB - DESIGN: A before-after prospective surveillance study to assess the impact of a multidimensional infection control approach for the reduction of catheter associated urinary tract infection (CAUTI) rates. SETTING: Pediatric intensive care units (PICUs) of hospital members of the International Nosocomial Infection Control Consortium (INICC) from 10 cities of the following 6 developing countries: Colombia, El Salvador, India, Mexico, Philippines, and Turkey. PATIENTS: PICU inpatients. METHODS: We performed a prospective active surveillance to determine rates of CAUTI among 3,877 patients hospitalized in 10 PICUs for a total of 27,345 bed-days. The study was divided into a baseline period (phase 1) and an intervention period (phase 2). In phase 1, surveillance was performed without the implementation of the multidimensional approach. In phase 2, we implemented a multidimensional infection control approach that included outcome surveillance, process surveillance, feedback on CAUTI rates, feedback on performance, education, and a bundle of preventive measures. The rates of CAUTI obtained in phase 1 were compared with the rates obtained in phase 2, after interventions were implemented. RESULTS: During the study period, we recorded 8,513 urinary catheter (UC) days, including 1,513 UC-days in phase 1 and 7,000 UC-days in phase 2. In phase 1, the CAUTI rate was 5.9 cases per 1,000 UC days, and in phase 2, after implementing the multidimensional infection control approach for CAUTI prevention, the rate of CAUTI decreased to 2.6 cases per 1,000 UC-days (relative risk, 0.43 [95% confidence interval, 0.21-1.0]), indicating a rate reduction of 57%. CONCLUSIONS: Our findings demonstrated that implementing a multidimensional infection control approach is associated with a significant reduction in the CAUTI rate of PICUs in developing countries. PMID- 22669232 TI - Findings of the International Nosocomial Infection Control Consortium (INICC), Part II: Impact of a multidimensional strategy to reduce ventilator-associated pneumonia in neonatal intensive care units in 10 developing countries. AB - Design. Before-after prospective surveillance study to assess the efficacy of the International Nosocomial Infection Control Consortium (INICC) multidimensional infection control program to reduce the rate of occurrence of ventilator associated pneumonia (VAP). Setting. Neonatal intensive care units (NICUs) of INICC member hospitals from 15 cities in the following 10 developing countries: Argentina, Colombia, El Salvador, India, Mexico, Morocco, Peru, Philippines, Tunisia, and Turkey. Patients. NICU inpatients. Methods. VAP rates were determined during a first period of active surveillance without the implementation of the multidimensional approach (phase 1) to be then compared with VAP rates after implementation of the INICC multidimensional infection control program (phase 2), which included the following practices: a bundle of infection control interventions, education, outcome surveillance, process surveillance, feedback on VAP rates, and performance feedback on infection control practices. This study was conducted by infection control professionals who applied National Health Safety Network (NHSN) definitions for healthcare associated infections and INICC surveillance methodology. Results. During phase 1, we recorded 3,153 mechanical ventilation (MV)-days, and during phase 2, after the implementation of the bundle of interventions, we recorded 15,981 MV-days. The VAP rate was 17.8 cases per 1,000 MV-days during phase 1 and 12.0 cases per 1,000 MV-days during phase 2 (relative risk, 0.67 [95% confidence interval, 0.50 0.91]; [Formula: see text]), indicating a 33% reduction in VAP rate. Conclusions. Our results demonstrate that an implementation of the INICC multidimensional infection control program was associated with a significant reduction in VAP rate in NICUs in developing countries. PMID- 22669233 TI - National survey of practices to prevent healthcare-associated infections in Thailand: the role of safety culture and collaboratives. AB - OBJECTIVE: To evaluate hospital characteristics and practices used by Thai hospitals to prevent catheter-associated urinary tract infection (CAUTI), central line-associated bloodstream infection (CLABSI), and ventilator-associated pneumonia (VAP), the 3 most common types of healthcare-associated infection (HAI) in Thailand. DESIGN: Survey. SETTING: Thai hospitals with an intensive care unit and 250 or more hospital beds. METHODS: Between January 1, 2010, and October 31, 2010, research nurses collected data from all eligible hospitals. The survey assessed hospital characteristics and practices to prevent CAUTI, CLABSI, and VAP. Ordinal logistic regression was used to assess relationships between hospital characteristics and use of prevention practices. RESULTS: A total of 204 (80%) of 256 hospitals responded. Most hospitals (93%) reported regularly using alcohol-based hand rub. The most frequently reported prevention practice by infection was as follows: for CAUTI, condom catheters in men (47%); for CLABSI, avoiding routine central venous catheter changes (85%); and for VAP, semirecumbent positioning (84%). Hospitals with peripherally inserted central catheter insertion teams were more likely to regularly use elements of the CLABSI prevention bundle. Greater safety scores were associated with regular use of several VAP prevention practices. The only hospital characteristic associated with increased use of at least 1 prevention practice for each infection was membership in an HAI collaborative. CONCLUSIONS: While reported adherence to hand hygiene was high, many of the prevention practices for CAUTI, CLABSI, and VAP were used infrequently in Thailand. Policies and interventions emphasizing specific infection prevention practices, establishing a strong institutional safety culture, and participating in collaboratives to prevent HAI may be beneficial. PMID- 22669235 TI - Trends in hospitalization for community-associated methicillin-resistant Staphylococcus aureus in New York City, 1997-2006: data from New York State's Statewide Planning and Research Cooperative System. AB - OBJECTIVE: To describe trends in hospitalizations with community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infection in New York City over 10 years and to explore the demographics and comorbidities of patients hospitalized with CA-MRSA infections. DESIGN: Retrospective analysis of hospital discharges from New York State's Statewide Planning and Research Cooperative System database from 1997 to 2006. PATIENTS: All patients greater than 1 year of age admitted to New York hospitals with diagnosis codes indicating MRSA who met the criteria for CA-MRSA on the basis of admission information and comorbidities. METHODS: We determined hospitalization rates and compared demographics and comorbidities of patients hospitalized with CA-MRSA versus those hospitalized with all other non-MRSA diagnoses by multivariable logistic regression. RESULTS: Of 18,226 hospitalizations with an MRSA diagnosis over 10 years, 3,579 (20%) were classified as community-associated. The CA-MRSA hospitalization rate increased from 1.47 to 10.65 per 100,000 people overall from 1997 to 2006. Relative to non MRSA hospitalizations, men, children, Bronx and Manhattan residents, the homeless, patients with human immunodeficiency virus (HIV) infection, and persons with diabetes had higher adjusted odds of CA-MRSA hospitalization. CONCLUSIONS: The CA-MRSA hospitalization rate appeared to increase between 1997 and 2006 in New York City, with residents of the Bronx and Manhattan, men, and persons with HIV infection or diabetes at increased odds of hospitalization with CA-MRSA. Further studies are needed to explore how changes in MRSA incidence, access to care, and other factors may have impacted these rates. PMID- 22669234 TI - Association between vancomycin-resistant Enterococci bacteremia and ceftriaxone usage. AB - OBJECTIVE: Vancomycin-resistant enterococci (VRE) have become a public health concern with implications for patient mortality and costs. Hospital antibiotic usage may impact VRE incidence, but the relationship is poorly understood. Animal investigations suggest that ceftriaxone may be associated with VRE proliferation. We measured antimicrobial usage and VRE bloodstream infection (VRE-BSI) incidence to test our hypothesis that increased ceftriaxone usage would be associated with a higher incidence of VRE-BSI. DESIGN: Retrospective cohort study. SETTING: University of Alabama at Birmingham Medical Center, a 900-bed urban tertiary care hospital. PARTICIPANTS: All patients admitted during the study period contributed data. METHODS: We conducted a retrospective analysis of antimicrobial usage and VRE-BSI from 2005 to 2008 (43 months). Antimicrobial usage was quantified as days of therapy (DOTs) per 1,000 patient-days. VRE-BSI incidence was calculated as cases per 1,000 patient-days. Negative binomial regression with adjustment for correlation between consecutive observations was used to measure the association between antimicrobial usage and VRE-BSI incidence at the hospital- and care-unit levels. RESULTS: VRE-BSI incidence increased from 0.06 to 0.17 infections per 1,000 patient-days. Hospital VRE-BSI incidence was associated with prior-month ceftriaxone DOTs (incidence rate ratio, 1.38 per 10 DOTs; P = .005). After controlling for ceftriaxone, prior-month cephalosporin usage (class) was not predictive of VRE-BSI (P = .70). Similarly, prior-month usage of piperacillin tazobactam, ceftazidime, cefepime, cefazolin, or vancomycin was not predictive of VRE-BSI when considered individually (P>= .4 for all comparisons). The final model suggests that type of intensive care unit was related to VRE-BSI incidence. CONCLUSIONS: Ceftriaxone usage in the prior month, but not cephalosporin (class) or vancomycin usage, was related to VRE-BSI incidence. These findings suggest that an antimicrobial stewardship program that limits ceftriaxone may reduce nosocomial VRE-BSI incidence. PMID- 22669236 TI - Serologic testing for protection against hepatitis B virus infection among students at a health sciences university in the United States. AB - OBJECTIVE: To evaluate hepatitis B vaccination coverage and documentation of vaccine-induced immunity. DESIGN: Retrospective cohort analysis. SETTING: Graduate school in the United States with programs in osteopathic medicine, dentistry, and allied health. METHODS: Data collected included demographics, dates of hepatitis B vaccine doses, and postvaccination concentrations of antibody to hepatitis B surface antigen (anti-HBs), with dates. The proportions of students with anti-HBs of 10 IU/L or more by demographics, age at vaccination, interval since completion of the primary series, and response to additional vaccine doses were compared. RESULTS: Of 3,452 students who matriculated during 2004-2009, 2,643 had complete data; 2,481 (93.9%) received 3 primary doses. Most were women (64.6%), US-born (85.6%), and white (63.2%); median age at receipt of the primary series was 14.5 years (interquartile range, 11.6-20.2 years) and at postvaccination testing was 23.2 years (interquartile range, 22.1-24.8 years). Of those who received 3 primary doses, 2,306 (92.9%) had an anti-HBs postvaccination concentration of 10 IU/L or more. Younger age at vaccination and longer time interval from vaccination to anti-HBs testing were associated with a postvaccination concentration of less than 10 IU/L (P< .001 and P = .0185, respectively, Cochran-Armitage test for trend). Almost all students (98.2%) who initially had less than 10 IU/L of anti-HBs, but then received at least 1 additional dose, had a follow-up anti-HBs concentration of 10 IU/L or more. CONCLUSIONS: Almost all students had serologic evidence of protection against hepatitis B virus infection; most were vaccinated as adolescents and were tested more than 10 years after vaccination. Among students with anti-HBs concentrations of less than 10 IU/L, nearly all had 10 IU/L or more after at least 1 additional vaccine dose. PMID- 22669237 TI - H1N1 influenza vaccine compliance among hospital- and non-hospital-based healthcare personnel. AB - BACKGROUND: The 2009 pandemic H1N1 influenza vaccine had lower uptake compared to seasonal influenza vaccine, and most studies examining uptake of H1N1 vaccine focused on hospital-based healthcare personnel (HCP). Determinants of H1N1 vaccine uptake among HCP in all work settings need to be identified so that interventions can be developed for use in encouraging uptake of future pandemic or emerging infectious disease vaccines. OBJECTIVE: To identify factors influencing nonhospital HCP H1N1 influenza vaccine compliance. DESIGN AND SETTING: An H1N1 influenza vaccine compliance questionnaire was administered to HCP working in myriad healthcare settings in March-June 2011. METHODS: Surveys were used to assess H1N1 influenza vaccine compliance and examine factors that predicted H1N1 influenza vaccine uptake. RESULTS: In all, 3,188 HCP completed the survey. Hospital-based HCP had higher compliance than did non-hospital-based personnel (Chi2 = 142.2, P < .001). In logistic regression stratified by hospital setting versus nonhospital setting, determinants of H1N1 vaccination among non hospital-based HCP included extent to which H1N1 vaccination was mandated or encouraged, perceived importance of vaccination, access to no-cost vaccine provided on-site, no fear of vaccine side effects, and trust in public health officials when they say that the influenza vaccine is safe. Determinants of hospital-based HCP H1N1 vaccine compliance included having a mandatory vaccination policy, perceived importance of vaccination, no fear of vaccine side effects, free vaccine, perceived seriousness of H1N1 influenza, and trust in public health officials. CONCLUSIONS: Non-hospital-based HCP versus hospital based HCP reasons for H1N1 vaccine uptake differed. Targeted interventions are needed to increase compliance with pandemic-related vaccines. PMID- 22669238 TI - Prospective approach to managing antimicrobial drug shortages. AB - Antimicrobial drug shortages continue to increase, with few new therapeutic options available. Nationally, proposals have been offered to alleviate drug shortages; however, these recommendations are unlikely to effect change in the near future. Thus, antimicrobial stewardship leaders in acute care hospitals must develop a prospective management strategy to lessen the impact of these shortages on patient care. Herein, we describe several resources available to aid professionals in antimicrobial stewardship and healthcare epidemiology to manage drug shortages. An effective approach should include prospectively tracking shortages and maximizing inventory by appropriately managing usage. Several tenets should underpin this management. Alternative agents should be rationally chosen before the inventory of the primary agent has reached zero, ethical considerations should be taken into account, and timely notification and communication with key stakeholders should occur throughout the prescribing and dispensing process. PMID- 22669239 TI - When should contact precautions and active surveillance be used to manage patients with multidrug-resistant enterobacteriaceae? PMID- 22669240 TI - Influenza vaccination coverage among health professionals before and after the A(H1N1) influenza pandemic in France. PMID- 22669241 TI - Neurosurgical case investigation of postflood pseudomeningitis due to mold. PMID- 22669243 TI - Logistic model of glucose-regulated C-peptide secretion: hysteresis pathway disruption in impaired fasting glycemia. AB - The present analysis tests the hypothesis that quantifiable disruption of the glucose-stimulated insulin-secretion dose-response pathway mediates impaired fasting glycemia (IFG) and type 2 diabetes mellitus (DM). To this end, adults with normal and impaired fasting glycemia (NFG, n = 30), IFG (n = 32), and DM (n = 14) were given a mixed meal containing 75 g glucose. C-peptide and glucose were measured over 4 h, 13 times in NFG and IFG and 16 times in DM (age range 50-57 yr, body mass index 28-32 kg/m(2)). Wavelet-based deconvolution analysis was used to estimate time-varying C-peptide secretion rates. Logistic dose-response functions were constructed analytically of the sensitivity, potency, and efficacy (in the pharmacological sense of slope, one-half maximal stimulation, and maximal effect) of glucose's stimulation of prehepatic insulin (C-peptide) secretion. A hysteresis changepoint time, demarcating unequal glucose potencies for onset and recovery pathways, was estimated simultaneously. According to this methodology, NFG subjects exhibited distinct onset and recovery potencies of glucose in stimulating C-peptide secretion (6.5 and 8.5 mM), thereby defining in vivo hysteresis (potency shift -2.0 mM). IFG patients manifested reduced glucose onset potency (8.6 mM), and diminished C-peptide hysteretic shift (-0.80 mM). DM patients had markedly decreased glucose potency (18.8 mM), reversal of C peptide's hysteretic shift (+4.5 mM), and 30% lower C-peptide sensitivity to glucose stimulation. From these data, we conclude that a dynamic dose-response model of glucose-dependent control of C-peptide secretion can identify disruption of in vivo hysteresis in patients with IFG and DM. Pathway-defined analytic models of this kind may aid in the search for prediabetes biomarkers. PMID- 22669242 TI - JAK/STAT3 pathway inhibition blocks skeletal muscle wasting downstream of IL-6 and in experimental cancer cachexia. AB - Cachexia, the metabolic dysregulation leading to sustained loss of muscle and adipose tissue, is a devastating complication of cancer and other chronic diseases. Interleukin-6 and related cytokines are associated with muscle wasting in clinical and experimental cachexia, although the mechanisms by which they might induce muscle wasting are unknown. One pathway activated strongly by IL-6 family ligands is the JAK/STAT3 pathway, the function of which has not been evaluated in regulation of skeletal muscle mass. Recently, we showed that skeletal muscle STAT3 phosphorylation, nuclear localization, and target gene expression are activated in C26 cancer cachexia, a model with high IL-6 family ligands. Here, we report that STAT3 activation is a common feature of muscle wasting, activated in muscle by IL-6 in vivo and in vitro and by different types of cancer and sterile sepsis. Moreover, STAT3 activation proved both necessary and sufficient for muscle wasting. In C(2)C(12) myotubes and in mouse muscle, mutant constitutively activated STAT3-induced muscle fiber atrophy and exacerbated wasting in cachexia. Conversely, inhibiting STAT3 pharmacologically with JAK or STAT3 inhibitors or genetically with dominant negative STAT3 and short hairpin STAT3 reduced muscle atrophy downstream of IL-6 or cancer. These results indicate that STAT3 is a primary mediator of muscle wasting in cancer cachexia and other conditions of high IL-6 family signaling. Thus STAT3 could represent a novel therapeutic target for the preservation of skeletal muscle in cachexia. PMID- 22669244 TI - The disposition index: from individual to population approach. AB - To correctly evaluate the glucose control system, it is crucial to account for both insulin sensitivity and secretion. The disposition index (DI) is the most widely accepted method to do so. The original paradigm (hyperbolic law) consists of the multiplicative product of indices related to insulin sensitivity and secretion, but more recently, an alternative formula has been proposed with the exponent alpha (power function law). Traditionally, curve-fitting approaches have been used to evaluate the DI in a population: the algorithmic implementations often introduce some critical issues, such as the assumption that one of the two indices is error free or the effects of the log transformation on the measurement errors. In this work, we review the commonly used approaches and show that they provide biased estimates. Then we propose a novel nonlinear total least square (NLTLS) approach, which does not need to use the approximations built in the previously proposed alternatives, and show its superiority. All of the traditional fit procedures, including NLTLS, account only for uncertainty affecting insulin sensitivity and secretion indices when they are estimated from noisy data. Thus, they fail when part of the observed variability is due to inherent differences in DI values between individuals. To handle this inevitable source of variability, we propose a nonlinear mixed-effects approach that describes the DI using population hyperparameters such as the population typical values and covariance matrix. On simulated data, this novel technique is much more reliable than the curve-fitting approaches, and it proves robust even when no or small population variability is present in the DI values. Applying this new approach to the analysis of real IVGTT data suggests a value of alpha significantly smaller than 1, supporting the importance of testing the power function law as an alternative to the simpler hyperbolic law. PMID- 22669245 TI - Estrogen targets fat mass and glucose metabolism by acting in the brain. PMID- 22669247 TI - Anandamide regulates the expression of GnRH1, GnRH2, and GnRH-Rs in frog testis. AB - Gonadotropin-releasing hormone (either GnRH1 or GnRH2) exerts a local activity in vertebrate testis, including human testis. Relationships between endocannabinoid (eCB) and GnRH systems in gonads have never been elucidated in any species so far. To reveal a cross-talk between eCBs and GnRH at testicular level, we characterized the expression of GnRH (GnRH1 and GnRH2) as well as GnRH receptor (GnRH-R1, -R2, and -R3) mRNA in the testis of the anuran amphibian Rana esculenta during the annual sexual cycle; furthermore, the corresponding transcripts were localized inside the testis by in situ hybridization. The possible endogenous production of the eCB, anandamide (AEA), was investigated in testis by analyzing the expression of its biosynthetic enzyme, Nape-pld. Incubations of testis pieces with AEA were carried out in the postreproductive period (June) and in February, when a new spermatogenetic wave takes place. In June, AEA treatment significantly decreased GnRH1 and GnRH-R2 mRNA, stimulated the transcription of GnRH2 and GnRH R1, and did not affect GnRH-R3 expression. In February, AEA treatment upregulated GnRH2 and GnRH-R3 mRNA, downregulated GnRH-R2, and did not affect GnRH1 and GnRH R1 expression. These effects were mediated by type 1 cannabinoid receptor (CB1) since they were fully counteracted by SR141716A (Rimonabant), a selective CB1 antagonist. In conclusion, eCB system modulates GnRH activity in frog testis during the annual sexual cycle in a stage-dependent fashion. PMID- 22669249 TI - Gas phase metal cluster model systems for heterogeneous catalysis. AB - Since the advent of intense cluster sources, physical and chemical properties of isolated metal clusters are an active field of research. In particular, gas phase metal clusters represent ideal model systems to gain molecular level insight into the energetics and kinetics of metal-mediated catalytic reactions. Here we summarize experimental reactivity studies as well as investigations of thermal catalytic reaction cycles on small gas phase metal clusters, mostly in relation to the surprising catalytic activity of nanoscale gold particles. A particular emphasis is put on the importance of conceptual insights gained through the study of gas phase model systems. Based on these concepts future perspectives are formulated in terms of variation and optimization of catalytic materials e.g. by utilization of bimetals and metal oxides. Furthermore, the future potential of bio-inspired catalytic material systems are highlighted and technical developments are discussed. PMID- 22669246 TI - Transformation of postingestive glucose responses after deletion of sweet taste receptor subunits or gastric bypass surgery. AB - The glucose-dependent secretion of the insulinotropic hormone glucagon-like peptide-1 (GLP-1) is a critical step in the regulation of glucose homeostasis. Two molecular mechanisms have separately been suggested as the primary mediator of intestinal glucose-stimulated GLP-1 secretion (GSGS): one is a metabotropic mechanism requiring the sweet taste receptor type 2 (T1R2) + type 3 (T1R3) while the second is a metabolic mechanism requiring ATP-sensitive K(+) (K(ATP)) channels. By quantifying sugar-stimulated hormone secretion in receptor knockout mice and in rats receiving Roux-en-Y gastric bypass (RYGB), we found that both of these mechanisms contribute to GSGS; however, the mechanisms exhibit different selectivity, regulation, and localization. T1R3(-/-) mice showed impaired glucose and insulin homeostasis during an oral glucose challenge as well as slowed insulin granule exocytosis from isolated pancreatic islets. Glucose, fructose, and sucralose evoked GLP-1 secretion from T1R3(+/+), but not T1R3(-/-), ileum explants; this secretion was not mimicked by the K(ATP) channel blocker glibenclamide. T1R2(-/-) mice showed normal glycemic control and partial small intestine GSGS, suggesting that T1R3 can mediate GSGS without T1R2. Robust GSGS that was K(ATP) channel-dependent and glucose-specific emerged in the large intestine of T1R3(-/-) mice and RYGB rats in association with elevated fecal carbohydrate throughout the distal gut. Our results demonstrate that the small and large intestines utilize distinct mechanisms for GSGS and suggest novel large intestine targets that could mimic the improved glycemic control seen after RYGB. PMID- 22669248 TI - Ablation of ghrelin receptor in leptin-deficient ob/ob mice has paradoxical effects on glucose homeostasis when compared with ablation of ghrelin in ob/ob mice. AB - The orexigenic hormone ghrelin is important in diabetes because it has an inhibitory effect on insulin secretion. Ghrelin ablation in leptin-deficient ob/ob (Ghrelin(-/-):ob/ob) mice increases insulin secretion and improves hyperglycemia. The physiologically relevant ghrelin receptor is the growth hormone secretagogue receptor (GHS-R), and GHS-R antagonists are thought to be an effective strategy for treating diabetes. However, since some of ghrelin's effects are independent of GHS-R, we have utilized genetic approaches to determine whether ghrelin's effect on insulin secretion is mediated through GHS-R and whether GHS-R antagonism indeed inhibits insulin secretion. We investigated the effects of GHS-R on glucose homeostasis in Ghsr-ablated ob/ob mice (Ghsr(-/ ):ob/ob). Ghsr ablation did not rescue the hyperphagia, obesity, or insulin resistance of ob/ob mice. Surprisingly, Ghsr ablation worsened the hyperglycemia, decreased insulin, and impaired glucose tolerance. Consistently, Ghsr ablation in ob/ob mice upregulated negative beta-cell regulators (such as UCP-2, SREBP-1c, ChREBP, and MIF-1) and downregulated positive beta-cell regulators (such as HIF 1alpha, FGF-21, and PDX-1) in whole pancreas; this suggests that Ghsr ablation impairs pancreatic beta-cell function in leptin deficiency. Of note, Ghsr ablation in ob/ob mice did not affect the islet size; the average islet size of Ghsr(-/-):ob/ob mice is similar to that of ob/ob mice. In summary, because Ghsr ablation in leptin deficiency impairs insulin secretion and worsens hyperglycemia, this suggests that GHS-R antagonists may actually aggravate diabetes under certain conditions. The paradoxical effects of ghrelin ablation and Ghsr ablation in ob/ob mice highlight the complexity of the ghrelin-signaling pathway. PMID- 22669250 TI - [Partial nephrectomy. Rationale and limitations of an organ-preserving approach]. AB - The rising incidence of renal cell cancer in recent decades has led to a revision in the therapy of this malignancy. For small renal masses, partial nephrectomy has become the standard surgical treatment instead of radical nephrectomy. This approach can lead to a higher overall survival due to preservation of renal function. Avoiding chronic kidney disease is mandatory for patients with benign or small non-aggressive tumors; however, partial nephrectomy correlates with higher complication rates and is conditioned by operator skills. The role of partial nephrectomy compared to radical nephrectomy is still to be established particularly for larger tumors. The results of studies so far are mostly based on non-randomized retrospective data. This article will present the pros and cons of partial nephrectomy and will focus on the steps required to promulgate the indications of nephron-sparing surgery. PMID- 22669251 TI - [Obesity and prostate cancer. Role of adipocytokines and clinical implications]. AB - Obesity is proposed as a possible risk factor for many tumors. The present review discusses the current knowledge on the clinical and biological impact of obesity on the development and progression of prostate cancer, the role of adipocyte derived hormones (adipocytokines) in this scenario and the resulting clinical implications. In addition, the results of own experimental and clinical studies on the involvement of adipocytokines (e.g. leptin, adiponectin) in the pathophysiology of prostate cancer are presented. It was found that patients who were diagnosed with prostate cancer at this clinic had higher serum leptin and lower serum adiponectin concentrations. These investigations and other studies have further shown that higher serum levels of the adipocytokine leptin were associated with larger prostate cancer volumes, high-grade classification, biochemical recurrence, metastasis and progression of metastatic prostate tumors, as well as increased mortality. Moreover, there was a strong correlation between the serum level of leptin and serum levels of prostate specific antigen (PSA). Leptin stimulated in vitro the proliferation and inhibited the apoptosis of prostate cancer cells in a dose and time-dependent manner, however, androgen resistant cell lines responded more strongly. At the molecular level, adipocytokines require the network of tyrosine kinases to accomplish the mitogenic and antiapoptotic effects in prostate cancer cells. Prominent members of the most important signal transduction cascades, such as MAPK, PI3-K and JAK/STAT are activated upon binding of leptin to its receptor on the cell membrane of prostate cancer cells. Adipocytokines such as leptin may serve as additional prognostic parameters for the evaluation of specific therapies for metastatic hormone refractory prostate cancer. The findings presented here are intended as a basis for further studies. PMID- 22669252 TI - Effect of volumetric water content and clover (Trifolium incarnatum) on the survival of Escherichia coli O157:H7 in a soil matrix. AB - Studies aimed at understanding Escherichia coli O157:H7 soil survival dynamics are paramount due to their inevitable introduction into the organic vegetable production systems via animal manure-based fertilizer. Therefore, a greenhouse study was conducted to determine the survival of E. coli O157:H7 in highly controlled soil matrices subjected to two variable environmental stressors: (1) soil volumetric water content (25 or 45 % VWC), and (2) the growth of clover (planted or unplanted). During the 7-week study, molecular-based qPCR analyses revealed that E. coli O157:H7 survival was significantly lower in soils maintained at either near water-holding capacity (45 % VWC) or under clover growth. The significant reduction under clover growth was only observed when E. coli populations were determined relative to all bacteria, indicating the need to further study the competition between E. coli O157:H7 and the total bacterial community in organic soils. Given the significant effect of clover on E. coli O157:H7 survival under different moisture conditions in this greenhouse-based study, this work highlights the antimicrobial potential of clover exudates in arable soils, and future work should concentrate on their specific mechanisms of inhibition; ultimately leading to the development of crop rotations/production systems to improve pre-harvest food safety and security in minimally processed, ready-to-eat and organic production systems. PMID- 22669254 TI - Virtual 3-D 18F-FDG PET/CT panendoscopy for assessment of the upper airways of head and neck cancer patients: a feasibility study. AB - PURPOSE: The aim of this study was to evaluate whether a virtual 3-D (18)F fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT panendoscopy is feasible and can be used for noninvasive imaging of the upper airways and pharyngeal/laryngeal tumours. METHODS: From (18)F-FDG PET/CT data sets of 40 patients (29 men, 11 women; age 61 +/- 9 years) with pharyngeal or laryngeal malignancies virtual 3-D (18)F-FDG PET/CT panendoscopies were reconstructed and the image processing time was measured. The feasibility of assessing the oral cavity, nasopharynx, tongue base, soft palate, pharyngeal tonsils, epiglottis, aryepiglottic folds, piriform sinus, postcricoid space, glottis, subglottis, trachea, bronchi and oesophagus and of detecting primary tumours was tested. Results of fibre-optic bronchoscopy and histology served as the reference standard. RESULTS: The nasopharynx, tongue base, soft palate, pharyngeal tonsils, epiglottis, subglottis and the tracheobronchial tree were accessible in all 40, and the aryepiglottic folds, posterior hypopharyngeal wall, postcricoid space, piriform sinus, glottis, oral cavity and oesophagus in 37, 37, 37, 37, 33, 16 and 0 patients, respectively. In all 12 patients with restricted fibre-optic evaluation due to being primarily intubated, the subglottis was accessible via virtual panendoscopy. The primary tumour was depicted in 36 of 40 patients (90 %). The mean processing time for virtual (18)F-FDG PET/CT panendoscopies was 145 +/- 98 s. CONCLUSION: Virtual (18)F-FDG PET/CT panendoscopy of the upper airways is technically feasible and can detect pharyngeal and laryngeal malignancies. This new tool can aid in the complete evaluation of the subglottic space in intubated patients and may be used for planning optical panendoscopies, biopsies and surgery in the future. PMID- 22669253 TI - Isolation and characterization of a novel bacteriophage phi4D lytic against Enterococcus faecalis strains. AB - In recent years, Enterococcus faecalis has emerged as an important opportunistic nosocomial pathogen capable of causing dangerous infections. Therefore, there is an urgent need to develop novel antibacterial agents to control this pathogen. Bacteriophages have very effective bactericidal activity and several advantages over other antimicrobial agents and so far, no serious or irreversible side effects of phage therapy have been described. The objective of this study was to characterize a novel virulent bacteriophage phi4D isolated from sewage. Electron microscopy revealed its resemblance to Myoviridae, with an isometric head (74 +/- 4 nm) and a long contractile tail (164 +/- 4 nm). The phi4D phage genome was tested using pulsed-field gel electrophoresis and estimated to be 145 +/- 2 kb. It exhibited short latent period (25 min) and a relatively small burst size (36 PFU/cell). Tests were conducted on the host range, multiplicities of infection (MOI), thermal stability, digestion of DNA by restriction enzymes, and proteomic analyses of this phage. The isolated phage was capable of infecting a wide spectrum of enterococcal strains. The results of these investigations indicate that phi4D is similar to other Myoviridae bacteriophages (for example phiEF24C), which have been successfully used in phagotherapy. PMID- 22669255 TI - Detection of cranial meningiomas: comparison of 68Ga-DOTATOC PET/CT and contrast enhanced MRI. AB - PURPOSE: PET imaging with somatostatin receptor ligands, such as (68)Ga-DOTATOC, is a well-established method for detection and target volume definition of meningiomas prior to radiotherapy. Since DOTATOC PET delivers a higher contrast between meningiomas and surrounding tissues than MRI, we conducted a retrospective analysis to compare the diagnostic accuracy of contrast-enhanced MRI (CE-MRI) with (68)Ga-DOTATOC PET/CT in patients with cranial meningiomas prior to radiotherapy. METHODS: Over a period of 6 years, 134 patients (20-82 years of age, 107 women and 27 men) underwent cranial CE-MRI and (68)Ga-DOTATOC PET/CT. To compare the two methods, the lesions considered typical of meningiomas visually were counted and analysed with respect to their location and SUVmax. RESULTS: In the 134 patients investigated by both modalities, 190 meningiomas were detected by (68)Ga-DOTATOC PET/CT and 171 by CE-MRI. With knowledge of the PET/CT data, the MRI scans were reinvestigated, which led to the detection of 4 of the 19 incidental meningiomas, resulting in an overall detection rate of 92 % of the meningioma lesions that were found by PET/CT. CONCLUSION: Ga-DOTATOC PET/CT demonstrated an improved sensitivity in meningioma detection when compared to CE-MRI. Tumours adjacent to the falx cerebri, located at the skull base or obscured by imaging artefacts or calcification are particularly difficult to detect by MRI. Therefore (68)Ga-DOTATOC PET/CT may provide additional information in patients with uncertain or equivocal results on MRI or could help to confirm a diagnosis of meningioma based on MRI or could help to confirm MRI-based diagnosis of meningiomas in cases of biopsy limitations. It is possible that not only radiotherapy and surgical planning, but also follow-up strategies would benefit from this imaging modality. PMID- 22669257 TI - A trapper keeper for TRAPP, its structures and functions. AB - During biosynthesis many membrane and secreted proteins are transported from the endoplasmic reticulum, through the Golgi and on to the plasma membrane in small transport vesicles. These transport vesicles have to undergo budding, movement, tethering, docking, and fusion at each organelle of the biosynthetic pathway. The transport protein particle (TRAPP) complex was initially identified as the tethering factor for endoplasmic reticulum (ER)-derived COPII vesicles, but the functions of TRAPP may extend to other areas of biology. Three forms of TRAPP complexes have been discovered to date, and recent advances in research have provided new insights on the structures and functions of TRAPP. Here we provide a comprehensive review of the recent findings in TRAPP biology. PMID- 22669258 TI - Tightrope act: autophagy in stem cell renewal, differentiation, proliferation, and aging. AB - Autophagy is a constitutive lysosomal catabolic pathway that degrades damaged organelles and protein aggregates. Stem cells are characterized by self-renewal, pluripotency, and quiescence; their long life span, limited capacity to dilute cellular waste and spent organelles due to quiescence, along with their requirement for remodeling in order to differentiate, all suggest that they require autophagy more than other cell types. Here, we review the current literature on the role of autophagy in embryonic and adult stem cells, including hematopoietic, mesenchymal, and neuronal stem cells, highlighting the diverse and contrasting roles autophagy plays in their biology. Furthermore, we review the few studies on stem cells, lysosomal activity, and autophagy. Novel techniques to detect autophagy in primary cells are required to study autophagy in different stem cell types. These will help to elucidate the importance of autophagy in stem cells during transplantation, a promising therapeutic approach for many diseases. PMID- 22669259 TI - Key role of integrin alpha(IIb)beta (3) signaling to Syk kinase in tissue factor induced thrombin generation. AB - The fibrin(ogen) receptor, integrin alpha(IIb)beta(3), has a well-established role in platelet spreading, aggregation and clot retraction. How alpha(IIb)beta(3) contributes to platelet-dependent coagulation is less well resolved. Here, we demonstrate that the potent suppressing effect of clinically used alpha(IIb)beta(3) blockers on tissue factor-induced thrombin generation is linked to diminished platelet Ca(2+) responses and phosphatidylserine (PS) exposure. The same blockers suppress these responses in platelets stimulated with collagen and thrombin receptor agonists, whereas added fibrinogen potentiates these responses. In platelets spreading on fibrinogen, outside-in alpha(IIb)beta(3) signaling similarly enhances thrombin-induced Ca(2+) rises and PS exposure. These responses are reduced in alpha(IIb)beta(3)-deficient platelets from patients with Glanzmann's thrombasthenia. Furthermore, the contribution of alpha(IIb)beta(3) to tissue factor-induced platelet Ca(2+) rises, PS exposure and thrombin generation in plasma are fully dependent on Syk kinase activity. Tyrosine phosphorylation analysis confirms a key role of Syk activation, which is largely but not exclusively dependent on alpha(IIb)beta(3) activation. It is concluded that the majority of tissue factor-induced procoagulant activity of platelets relies on Syk activation and ensuing Ca(2+) signal generation, and furthermore that a considerable part of Syk activation relies on alpha(IIb)beta(3) signaling. These results hence point to a novel role of Syk in integrin-dependent thrombin generation. PMID- 22669260 TI - Dynamics of ESCRT proteins. AB - Proteins of the ESCRT (endosomal sorting complex required for transport) complex function in membrane fission processes, such as multivesicular body (MVBs) formation, the terminal stages of cytokinesis, and separation of enveloped viruses from the plasma membrane. In mammalian cells, the machinery consists of a network of more than 20 proteins, organized into three complexes (ESCRT-I, -II, and -III), and other associated proteins such as the ATPase vacuolar protein sorting 4 (Vps4). Early biochemical studies of MVBs biogenesis in yeast support a model of sequential recruitment of ESCRT complexes on membranes. Live-cell imaging of ESCRT protein dynamics during viral budding and cytokinesis now reveal that this long-standing model of sequential assembly and disassembly holds true in mammalian cells. PMID- 22669261 TI - Regulated expression and neural functions of human natural killer-1 (HNK-1) carbohydrate. AB - Human natural killer-1 (HNK-1) carbohydrate, comprising a unique trisaccharide HSO(3)-3GlcAbeta1-3Galbeta1-4GlcNAc, shows well-regulated expression and unique functions in the nervous system. Recent studies have revealed sophisticated and complicated expression mechanisms for HNK-1 glycan. Activities of biosynthetic enzymes are controlled through the formation of enzyme-complexes and regulation of subcellular localization. Functional aspects of HNK-1 carbohydrate were examined by overexpression, knockdown, and knockout studies of these enzymes. HNK 1 is involved in several neural functions such as synaptic plasticity, learning and memory, and the underlying molecular mechanisms have been illustrated upon identification of the target carrier glycoproteins of HNK-1 such as the glutamate receptor subunit GluA2 or tenascin-R. In this review, we describe recent findings about HNK-1 carbohydrate that provide further insights into the mechanism of its expression and function in the nervous system. PMID- 22669262 TI - Tactual perception: a review of experimental variables and procedures. AB - This paper reviews the literature on tactual perception. Throughout this review, we will highlight some of the most relevant aspects in the touch literature: type of stimuli; type of participants; type of tactile exploration; and finally, the interaction between touch and other senses. Regarding type of stimuli, we will analyse studies with abstract stimuli such as vibrations, with two- and three dimensional stimuli, and also concrete stimuli, considering the relation between familiar and unfamiliar stimuli and the haptic perception of faces. Under the "type of participants" topic, we separated studies with blind participants, studies with children and adults, and also performed an overview of sex differences in performance. The type of tactile exploration is explored considering conditions of active and passive touch, the relevance of movement in touch and the relation between haptic exploration and time. Finally, interactions between touch and vision, touch and smell and touch and taste are explored in the last topic. The review ends with an overall conclusion on the state of the art for the tactual perception literature. With this work, we intend to present an organised overview of the main variables in touch experiments, compiling aspects reported in the tactual literature, and attempting to provide both a summary of previous findings, and a guide to the design of future works on tactual perception and memory, through a presentation of implications from previous studies. PMID- 22669263 TI - Expansion of a globally pervasive grass occurs without substantial trait differences between home and away populations. AB - The global expansion of species beyond their ancestral ranges can derive from mechanisms that are trait-based (e.g., post-establishment evolved differences compared to home populations) or circumstantial (e.g., propagule pressure, with no trait-based differences). These mechanisms can be difficult to distinguish following establishment, but each makes unique predictions regarding trait similarity between ancestral ('home') and introduced ('away') populations. Here, we tested for trait-based population differences across four continents for the globally distributed grass Dactylis glomerata, to assess the possible role of trait evolution in its worldwide expansion. We used a common-environment glasshouse experiment to quantify trait differences among home and away populations, and the potential relevance of these differences for competitive interactions. Few significant trait differences were found among continents, suggesting minimal change during global expansion. All populations were polyploids, with similar foliar carbon:nitrogen ratios (a proxy for defense), chlorophyll content, and biomass. Emergence time and growth rate favored home populations, resulting in their competitive superiority over away populations. Small but significant trait differences among away populations suggest different introductory histories or local adaptive responses following establishment. In summary, the worldwide distribution of this species appears to have arisen from its pre-adapted traits promoting growth, and its repeated introduction with cultivation and intense propagule pressure. Global expansion can thus occur without substantial shifts in growth, reproduction, or defense. Rather than focusing strictly on the invader, invasion success may also derive from the traits found (or lacking) in the recipient community and from environmental context including human disturbance. PMID- 22669265 TI - Transcatheter embolization of extensive left gastric artery collaterals presenting with massive upper gastrointestinal bleed. AB - We report a case of extensive left gastric artery collaterals that were formed in the region of gastric fundus due to splenic artery occlusion and resulted in massive hematemesis. These collaterals were thought to be portosystemic collaterals related to portal hypertension during upper endoscopy study and single-phase venous computed tomography studies. The collaterals were treated by transcatheter endovascular coil embolization. Our case highlights the importance of recognizing and differentiating left gastric artery collaterals from gastric venous varices as a cause of hematemesis since the treatment approach for each condition is totally different. It also introduces the feasibility of percutaneous left gastric artery embolization as a treatment for this condition, without the need for surgical splenectomy and partial gastrectomy which have a higher mortality and morbidity. PMID- 22669266 TI - Innumerable bilateral pulmonary arteriovenous malformations: percutaneous transcatheter embolization using Amplatzer vascular plug. AB - We report an unusual and distinct case of innumerable bilateral pulmonary arteriovenous malformation (PAVM) in a 42-year-old patient presenting with significant right-to-left shunt resulting in severe dyspnea and with a history of stroke due to paradoxical embolization related to his PAVM. Because it was impossible to treat all his PAVMs, our aim was to treat those with a feeding artery measuring 3 mm or more in diameter, aiming to improve the patient's dyspnea and decrease the risk of paradoxical embolization. We safely and successfully embolized 8 of the patient's PAVMs, using a single Amplatzer vascular plug for each PAVM. The procedure did not result in significant improvement of the patient's symptoms. In similar cases with innumerable PAVMs, the expectations of symptom relief should be lowered and the patient should be informed that treatment will only offer protection from paradoxical embolization. To our knowledge, there are no similar cases previously described in the literature. PMID- 22669264 TI - The role of sleep problems and circadian clock genes in childhood psychiatric disorders. AB - CLOCK gene research and the analysis of circadian rhythmicity on the behavioural, cellular and molecular level are increasingly contributing to accumulate clinically relevant knowledge in the fields of neuroscience, psychopharmacology and adult psychiatry. However, the role of circadian phenomena, including sleep alterations in mental disorders during childhood and adolescence remains largely enigmatic. Fortunately, recent publications have addressed this problem and there is now some evidence available highlighting the relevance of CLOCK genes in conditions, such as ADHD, mood disorders, schizophrenia and anxiety disorders. PMID- 22669267 TI - Giant true brachial artery aneurysm. AB - True brachial artery aneurysms (BAAs) are uncommon peripheral vessel aneurysms that typically occur in the setting of injury. While its relationship with trauma and infectious etiologies are well defined, the association between arteriovenous fistulas (AVFs) and BAA is less well understood. We present a case of a giant true BAA that presented several years post-AVF ligation. A review of BAA, its association with AVF, and its management follows. PMID- 22669268 TI - Retroperitoneal trapdoor endarterectomy for paravisceral "coral-reef" aortic plaque. AB - A 67-year-old woman presented to the emergency room with progressive claudication, chest pain, and flash-pulmonary edema. Her past medical history was significant for poorly controlled hypertension requiring multiple antihypertensive medications, renal insufficiency, and tobacco abuse. Diagnostic evaluation revealed an extensive exophytic plaque localized to the paravisceral aorta resulting in high-grade stenoses of the proximal aorta as well as the celiac, superior mesenteric, and left renal arteries. She underwent surgical revascularization through a retroperitoneal aortic exposure and trapdoor aortic endarterectomy, the technical conduct of which is described in this manuscript. The patient recovered uneventfully and experienced resolution of her claudication and pulmonary symptoms, improved blood pressure control, and normalization of her creatinine. Review of the medical literature pertaining to management of proximal occlusive disease of the abdominal aorta is discussed. PMID- 22669269 TI - Sulcus vocalis: excision, primary suture and medialization laryngoplasty: personal experience with 44 cases. AB - This is a prospective, cohort study to present personal experience on excision of sulcus, primary suture of defect and medialization laryngoplasty. An article about this subject is not present in medical literature. Forty-four patients with sulcus vocalis who were operated on by excision, primary suture of epithelial defect and medialization laryngoplasty were included. Pre- and postoperative evaluations included GRBAS, VHI-30, stroboscopy, aerodynamic and acoustic analysis. Grade, roughness and breathiness of GRBAS were significantly better postoperatively (p < 0.05), whereas asthenia and strain were not (p > 0.05). All VHI-30 results decreased significantly after surgery (p < 0.01). Glottal closure and mucosal wave amplitude during stroboscopy improved significantly postoperatively (p < 0.05), whereas symmetry and periodicity did not (p > 0.05). Maximum phonation time, mean airflow rate, mean efficiency and mean pressure of aerodynamic analysis improved significantly after surgery (p < 0.05). However, mean resistance and mean power were not significantly different (p > 0.05). All parameters, except F (0) and soft phonation index during acoustic analysis with /a/, and except F (0), voice turbulence index and soft phonation index during acoustic analysis with constant phrase improved significantly after surgery (p < 0.05). Surgical treatments of sulcus vocalis are not satisfactory enough, yet. Excision of sulcus, primary suture of epithelial defect and medialization laryngoplasty is one of the successful surgical options. Intact vocal ligament at the bottom of sulcus is a good prognostic sign for good postoperative voice result. Success appears to depend on how long, how wide and how deep sulcus is. Good patient selection may increase the percentage of happy patients. PMID- 22669270 TI - Quality of dying in head and neck cancer patients: the role of surgical palliation. AB - To study the role of surgery for symptom palliation in patients with advanced head and neck malignancy. Between 2000 and 2011, patients with locoregionally advanced cancer in the head and neck region, who chose surgical palliation for symptom control, were studied retrospectively. During the study period, 52 patients were included. The index tumour included carcinoma of the maxilla (23.1 %), tongue (19.2 %), larynx/hypopharynx (15.4 %), post-radiation sarcoma (11.5 %), primary sarcoma (11.5 %), carcinoma of the lower alveolus (11.5 %), nasal mucosal melanoma (3.9 %) and metastatic tumour in the head and neck region (3.9 %). The major symptoms included bleeding (53.9 %), tumour pain (19.2 %), dysphagia (11.5 %), non-healing ulcerations (7.7 %), airway obstruction (5.8 %) and pathological fracture of the mandible (1.9 %). Ligation of the carotid artery was performed in 10 patients, complete resection of tumour in 35, and surgical debulking of the tumour in 7 patients. Mean survival of the patients was 5.6 months. The majority of the patients achieved satisfactory and persistent control of symptoms. One patient died from pneumonia during the hospital stay, and the rest were discharged after a mean duration of 16.4 days. In selected patients, surgery is effective in palliating symptoms which are otherwise difficult to manage. Detailed planning and good communication is the key to success in improving the quality of dying. PMID- 22669271 TI - Quality of life and patients' satisfaction after otoplasty. AB - The objective of the study was to present the long-term results of satisfaction and quality of life of patients after otoplasty due to protuberant ears. A retrospective study at an academic tertiary referral centre is presented. A total of 164 patients were followed up after otoplasty due to ear dysplasia grade I. The validated questionnaires SF-36 and Patient Outcomes of Surgery-head/neck (POS) were applied to evaluate the quality of life and the patients' satisfaction after therapy. The comparison of preoperative and postoperative quality of life measured by POS showed significantly higher scores after surgery than before, independent of gender, age or experience of the surgeon. The patients' satisfaction with the surgical outcome showed high values in all subgroups. Except for "vitality", the SF-36 showed for all other items higher values of postoperative quality of life for patients after otoplasty than the German control population. With this study, we were able to demonstrate that health related quality of life of patients is significantly increased by otoplasty. This finding is most pronounced in early childhood (children younger than 10 years of age), but independent of gender, experience of the surgeon or whether a revision or a primary case was treated. The method of performing otoplasty as described in this paper has been used in our institution for many years. It is adapted to the specific pathology and combines resection with suture techniques. To confirm and complement our results and increase the knowledge in this field of surgery, a prospective study is not only needed but currently performed. PMID- 22669273 TI - The risk of overweight and obesity in children after tonsillectomy: a cross sectional study. AB - The aim of this cross-sectional study was to determine the prevalence of tonsillectomy among secondary school children and to investigate whether tonsillectomy with or without adenoidectomy is a risk factor for childhood obesity. A total of 27 secondary schools with 12,296 students between the ages 11 and 17 were screened in Denizli, Turkey. We determined 129 students who had undergone tonsillectomy; each student was matched with two healthy control subjects of the same age and sex (n = 258). A 28-item questionnaire on nutrition and physical exercise was completed by the parents. Age-adjusted body mass index and waist circumference percentiles of Turkish boys and girls were used for the assessment of overweight and obesity. The prevalence of tonsillectomy was 1.0 %. There was no significant relationship between having tonsillectomy and being overweight or obese and physical exercise and screen time (p > 0.05 for each). Logistic regression analyses suggested no significant effect of tonsillectomy on overweight or obesity of the subjects (p > 0.05). It seems that tonsillectomy had no effect on overweight and obesity among children. PMID- 22669272 TI - Intratympanic dexamethasone perfusion versus injection for treatment of refractory sudden sensorineural hearing loss. AB - Intratympanic steroid treatment for the sudden sensorineural hearing loss (SSNHL) has a long history and many techniques have been developed. The efficacies are varied in different studies owing to different criteria, steroid type and dose, delivery methods, or absence of comparison groups. Recently, animal experiments suggested that continuous delivery systems produce the higher inner ear drug concentrations than other ways. This study was aimed at evaluating the efficacies of intratympanic dexamethasone perfusion versus injection for treatment of refractory sudden sensorineural hearing loss (RSSNHL). A total of 136 patients were enrolled in this nonrandomized, prospective, controlled study. Thirty-two patients were treated with continuous intratympanic dexamethasone perfusion via round window microcatheter by an electronic pump at a rate of 10 MUl/min twice daily for 7 days and 34 patients underwent intratympanic dexamethasone injection of the same dosage. Seventy patients who refused to undertake further treatment were selected as a control group. Pure-tone audiometry results were obtained before and after treatments. Minimum follow-up time from the last treatment was 1 month. There were no serious adverse events in the treatment groups. Hearing improvement rate (HIR) of SSNHL in perfusion group was 40.6 %, which was significantly higher than in the injection and control groups (20.6 and 7.7 %, respectively). HIR had no relation with sex, age, and associated symptoms. Results indicated that intratympanic dexamethasone perfusion by external electronic pump with gelatin sponge placement in round window niche is an efficacious and safe method for the treatment of RSSNHL, showing superiority to simple injection through the drum. PMID- 22669274 TI - Multidetector CT of the heart: spectrum of benign and malignant cardiac masses. AB - Recent innovations in multidetector 3D CT have improved the spatial and temporal resolution of cardiac computed tomography (CT), which results in greater frequency of mass lesion identification and provides a new opportunity for more precise characterization. Although cardiac masses are rare entities, patients with cardiac masses may present with acute symptoms and may be encountered by emergency radiologists. The objectives of this article are to review the CT appearance of cardiac masses and the role of volumetric MDCT with 3D rendering to define characteristic features and provide a practical approach to formulating a differential diagnosis. PMID- 22669275 TI - Can exotic phytoseiids be considered 'benevolent invaders' in perennial cropping systems? AB - Numerous natural enemies were adopted worldwide for the control of major pests, including exotic phytoseiid species (Acari: Mesostigmata: Phytoseiidae) that had been moved from continent to continent in protected and perennial agricultural systems. However, relatively fewer successes were recorded in perennial agricultural systems. In this manuscript we focus on the question: Can and will exotic phytoseiids provide better pest control than indigenous species in perennial agricultural systems? To answer this question, we review the efficacy of biological control efforts with phytoseiids in several case studies, where exotic and indigenous species were used against pests on indigenous host plants and some crops that were historically or recently introduced. Related factors affecting predator establishment, such as intraguild predation and pesticide effects are discussed, as well as the potential negative effects of exotic species releases on biological control and their impact on the indigenous natural fauna. On citrus, apple, grape and cassava exotic phytoseiids have enhanced biological control without negatively affecting indigenous species of natural enemies, except for the case of Euseius stipulatus (Athias-Henriot) on citrus that displaced Euseius hibisci (Chant) in a limited region of coastal California, USA, the latter considered to be an inferior biocontrol agent of Panonychus citri Koch. Phytoseiulus persimilis Athias-Henriot on gorse, an invasive weed, is perhaps the only recorded case of a negative effect of an established exotic phytoseiid on biological control. PMID- 22669276 TI - Population dynamics of Aceria guerreronis (Acari: Eriophyidae) and other mites associated with coconut fruits in Una, state of Bahia, northeastern Brazil. AB - Aceria guerreronis Keifer is a major coconut pest in the Americas, Africa and some Asian countries, and occurs in high population levels in northeastern Brazil. The determination of the climatic conditions that favorably affect its population growth and the prevalence and abundance of predatory mites can promote more efficient control practices. Our objective was to evaluate the pattern of occurrence and population dynamics of A. guerreronis, their associated predators and other mites during a 2 year period in a hybrid coconut plantation in the municipality of Una, state of Bahia, northeastern Brazil. Monthly samples of fruits were taken from June 2008 to May 2010 for qualitative and quantitative evaluation of mites. Aceria guerreronis represented 99.9 % of the mites. An average density of 1,117 mites per fruit and a maximum of 23,596 mites per fruit indicated that the level of infestation can be high in Bahia. Bdella ueckermanni Hernandes, Daud and Feres was the most abundant and frequent predator. Population increase of A. guerreronis was directly related to the temperature rise and inversely related to both the increase of air relative humidity and rainfall. The highest population densities occurred from November to March. The largest A. guerreronis populations occurred in fruits with 32 and 48 % of damaged surface. The relationship between prevailing wind direction and incidence of A. guerreronis could not be corroborated or refuted. PMID- 22669277 TI - Tiadinil, a plant activator of systemic acquired resistance, boosts the production of herbivore-induced plant volatiles that attract the predatory mite Neoseiulus womersleyi in the tea plant Camellia sinensis. AB - Plants respond with various defense mechanisms to pathogenic or herbivorous attack. Some chemicals called plant activators that induce the plant defense response against pathogens have been commercially used to protect plants. Here we studied the effects of tiadinil (TDL) on defense mechanisms against herbivores. TDL suppresses pathogenic fungi on tea leaves by inducing defense mechanisms. We used one of the major trophic systems in tea consisting of the herbivorous mite, Tetranychus kanzawai, and the predatory mite, Neoseiulus womersleyi. TDL enhanced the production of herbivore-induced plant volatiles that attract predatory mites. The predatory mites preferred the T. kanzawai-induced volatiles from TDL-treated plants to those produced by untreated plants. These results suggest that TDL activates the plant defense response via an indirect process mediated by plant volatiles that attract natural enemies of the herbivores. In contrast, the oviposition rate, adult maturation rate, and sex ratio of T. kanzawai were not affected by TDL treatment. These results suggest that TDL did not activate any direct defense against the herbivorous mite. PMID- 22669278 TI - Tripartite associations among bacteriophage WO, Wolbachia, and host affected by temperature and age in Tetranychus urticae. AB - A phage density model of cytoplasmic incompatibility (CI), which means lytic phages reduce bacterial density associated with CI, significantly enhances our understanding of the tripartite associations among bacteriophage WO, Wolbachia and host. However, WO may alternate between lytic and lysogenic life cycles or change phage production under certain conditions including temperature, host age and host species background. Here, extreme temperatures can induce an alteration in the life cycle of WO and change the tripartite associations among WO, Wolbachia and CI. Based on the accumulation of the WO load, WO can transform into the lytic life cycle with increasing age. These findings confirmed that the environment plays an important role in the associations among WO, Wolbachia and host. PMID- 22669279 TI - Intraguild predation and cannibalism between the predatory mites Neoseiulus neobaraki and N. paspalivorus, natural enemies of the coconut mite Aceria guerreronis. AB - Neoseiulus neobaraki and N. paspalivorus are amongst the most common phytoseiid predators of coconut mite, Aceria guerreronis, found in the spatial niche beneath coconut fruit bracts. Both predators may occur on the same coconut palms in Benin and Tanzania and are therefore likely to interact with each other. Here, we assessed cannibalism and intraguild predation (IGP) of the two predators in the absence and presence of their primary prey A. guerreronis. In the absence of the shared extraguild prey, A. guerreronis, N. neobaraki killed 19 larvae of N. paspalivorus per day and produced 0.36 eggs/female/day, while the latter species killed only 7 larvae of the former and produced 0.35 eggs/female/day. Presence of A. guerreronis only slightly decreased IGP by N. neobaraki but strongly decreased IGP by N. paspalivorus, which consumed 4-7 times less IG prey than N. neobaraki. Resulting predator offspring to IG prey ratios were, however, 4-5 times higher in N. paspalivorus than N. neobaraki. Overall, provision of A. guerreronis increased oviposition in both species. In the cannibalism tests, in the absence of A. guerreronis, N. neobaraki and N. paspalivorus consumed 1.8 and 1.2 conspecific larvae and produced almost no eggs. In the presence of abundant herbivorous prey, cannibalism dramatically decreased but oviposition increased in both N. neobaraki and N. paspalivorus. In summary, we conclude that (1) N. neobaraki is a much stronger intraguild predator than N. paspalivorus, (2) cannibalism is very limited in both species, and (3) both IGP and cannibalism are reduced in the presence of the common herbivorous prey with the exception of IGP by N. neobaraki, which remained at high levels despite presence of herbivorous prey. We discuss the implications of cannibalism and IGP on the population dynamics of A. guerreronis and the predators in view of their geographic and within-palm distribution patterns. PMID- 22669280 TI - Diversity and seasonal patterns of ticks parasitizing wild birds in western Portugal. AB - The diversity and abundance of questing ticks and ticks parasitizing birds was assessed during 1 year in two recreational forests in western Portugal, a suburban forest and an enclosed game area. The aim of this study was to assess the distribution and seasonality of tick species and to understand the role of bird species as hosts for ticks. Ixodes ricinus was the most abundant questing tick collected in the enclosed game area, whereas in the suburban forest, only three ticks were collected by blanket dragging. Tick species parasitizing birds included I. ricinus, I. frontalis, I. arboricola, I. acuminatus, Haemaphysalis punctata, Hyalomma marginatum and H. lusitanicum. This is the first record of I. arboricola in Portugal. Tick prevalence and intensity of infestation differed between study areas and was higher in birds from the game area where a large population of deer and wild boar may support tick populations. Ground and shrub dwelling bird species such as Turdus merula, Erithacus rubecula and Sylvia melanocephala were the most heavily parasitized by ticks, but the importance of different bird species as hosts of larvae and nymphs of I. ricinus and I. frontalis differed. Therefore, different bird species may contribute differently for tick population maintenance. PMID- 22669281 TI - Esterase profile of Rhipicephalus (Boophilus) microplus populations collected from Northern India exhibiting varied susceptibility to deltamethrin. AB - Rhipicephalus (Boophilus) microplus is an economically important ectoparasite of cattle. Chemical acaricides remain the most practical method for control of these pests. During past two decades there have been increasing reports of resistance development against synthetic pyrethroids in tick populations of this species throughout the world. A study was conducted to determine the level of susceptibility of R. (B.) microplus to deltamethrin collected from different geographical locations of northern India. LPT bioassay results revealed LC(50) values of deltamethrin ranging from 0.035 to 0.00037 % A.I. Esterase profile of the tick larval extracts using native PAGE, revealed 5 bands of esterase activity designated EST-5 to EST-1A. Inhibitory tests recognized EST-1, EST-2 and EST-3 as Acetylcholinesterases (AchEs), EST-4 and EST-5 as Carboxylesterases (CaEs). The band intensity varied between tick populations of various locations, being more intense in case of the resistant populations. An extra band of esterase activity (EST-1A) was obtained in larval extracts of ticks from 3 locations. This increased esterase activity may be involved in the resistance development in these tick populations. Acaricide resistance is a multi-factorial phenomenon, thus other causes of increased resistance like sodium channel mutation and reduced drug penetration (e.g. cuticle thickening) and behavioural changes (e.g. avoiding the pesticides) are to be tested in future in order to confirm the basic cause of the resistance development in these acaricide resistant tick populations. PMID- 22669282 TI - Direct scaffolding of biomimetic hydroxyapatite-gelatin nanocomposites using aminosilane cross-linker for bone regeneration. AB - Hydroxyapatite-gelatin modified siloxane (GEMOSIL) nanocomposite was developed by coating, kneading and hardening processes to provide formable scaffolding for alloplastic graft applications. The present study aims to characterize scaffolding formability and mechanical properties of GEMOSIL, and to test the in vitro and in vivo biocompatibility of GEMOSIL. Buffer Solution initiated formable paste followed by the sol-gel reaction led to a final hardened composite. Results showed the adequate coating of aminosilane, 11-19 wt%, affected the cohesiveness of the powders and the final compressive strength (69 MPa) of the composite. TGA and TEM results showed the effective aminosilane coating that preserves hydroxyapatite-gelatin nanocrystals from damage. Both GEMOSIL with and without titania increased the mineralization of preosteoblasts in vitro. Only did titania additives revealed good in vivo bone formation in rat calvarium defects. The scaffolding formability, due to cohesive bonding among GEMOSIL particles, could be further refined to fulfill the complicated scaffold processes. PMID- 22669283 TI - Preparation and antibiotic drug release of mineralized collagen coatings on titanium. AB - In this study, a mineralized collagen coating was electrolytically deposited onto titanium. The results showed that the mineralized collagen coatings with dense or porous morphology could be obtained. The mineral phase was mainly hydroxyapatite. In vitro evaluation showed the mineralized collagen coatings were stable in Kokubo's simulated body fluid, and displayed a good cytocompatibility in the cell multiplication test. The mineralized collagen coatings loaded with vancomycin hydrochloride showed an inhibitory effect on the growth of S. aureus. The present mineralized collagen coating demonstrates good suitability for surface modification of orthopedic metal implants. PMID- 22669284 TI - In vitro behaviour of three biocompatible glasses in composite implants. AB - Poly(L,DL-lactide) composites containing filler particles of bioactive glasses 45S5 and S53P4 were compared with a composite containing a slowly dissolving glass S68. The in vitro reactivity of the composites was studied in simulated body fluid, Tris-buffered solution, and phosphate buffered saline. The high processing temperature induced thermal degradation giving cavities in the composites containing 45S5 and S53P4, while good adhesion of S68 to the polymer was observed. The cavities partly affected the in vitro reactivity of the composites. The degradation of the composites containing the bioactive glasses was faster in phosphate buffered saline than in the two other solutions. Hydroxyapatite precipitation suggesting bone tissue bonding capability was observed on these two composites in all three solutions. The slower dissolution of S68 glass particles and the limited hydroxyapatite precipitation suggested that this glass has potential as a reinforcing composition with the capability to guide bone tissue growth in biodegradable polymer composites. PMID- 22669285 TI - Biocompatibility and biodegradation studies of PCL/beta-TCP bone tissue scaffold fabricated by structural porogen method. AB - Three-dimensional printer (3DP) (Z-Corp) is a solid freeform fabrication system capable of generating sub-millimeter physical features required for tissue engineering scaffolds. By using plaster composite materials, 3DP can fabricate a universal porogen which can be injected with a wide range of high melting temperature biomaterials. Here we report results toward the manufacture of either pure polycaprolactone (PCL) or homogeneous composites of 90/10 or 80/20 (w/w) PCL/beta-tricalcium phosphate (beta-TCP) by injection molding into plaster composite porogens fabricated by 3DP. The resolution of printed plaster porogens and produced scaffolds was studied by scanning electron microscopy. Cytotoxicity test on scaffold extracts and biocompatibility test on the scaffolds as a matrix supporting murine osteoblast (7F2) and endothelial hybridoma (EAhy 926) cells growth for up to 4 days showed that the porogens removal process had only negligible effects on cell proliferation. The biodegradation tests of pure PCL and PCL/beta-TCP composites were performed in DMEM with 10 % (v/v) FBS for up to 6 weeks. The PCL/beta-TCP composites show faster degradation rate than that of pure PCL due to the addition of beta-TCP, and the strength of 80/20 PCL/beta-TCP composite is still suitable for human cancellous bone healing support after 6 weeks degradation. Combining precisely controlled porogen fabrication structure, good biocompatibility, and suitable mechanical properties after biodegradation, PCL/beta-TCP scaffolds fabricated by 3DP porogen method provide essential capability for bone tissue engineering. PMID- 22669286 TI - Reproducibility of multifocal VEP latency using different stimulus presentations. AB - The aims of the article were to study the reproducibility of latency of multifocal visual evoked potential (mfVEP) recorded using different stimulus presentations and to identify the peak with least variability. Ten normal subjects, aged between 22 and 52 years (mean age 32 +/- 8.37 years), participated in the study. All subjects underwent mfVEP testing with pattern reversal and pattern pulse stimulus presentations. The stimulus subtends 26 degrees from fixation and includes 24 segments. Only the vertical channel was recorded on all subjects. Testing was repeated after 1-2 weeks. Only the right eye of all subjects was analysed. Segments with low signal-to-noise ratios (SNR < 1.5) were excluded from analysis. The latencies were analysed to confirm values from the same peak for the two tests. The latency values were then analysed for the start of the response, the first peak and the second peak. The waveforms were reproducible throughout the field. Reproducibility of latency at the "start of the response" was significantly lesser than the first and the second peaks studied, while the reproducibility of latency at the first peak was not statistically different from the second peak for either pattern reversal or pattern pulse stimulation. The latency values were not different between the first and the second sessions for either pattern reversal or pattern pulse stimulation for any of the peaks. The pattern reversal stimulus presentation produced less variability in latency. The first peak is the most reproducible among the three measures in both the stimulus presentation. PMID- 22669288 TI - A dicranopteris-like Fe-Sn-Sb-P alloy as a promising anode for lithium ion batteries. AB - A novel dicranopteris-like Fe-Sn-Sb-P composite was prepared, for the first time, by electrodeposition. The quaternary Fe-Sn-Sb-P alloy of multiphase displayed an excellent cycling performance as an anode of Li ion secondary batteries. PMID- 22669287 TI - Multimodal fundus imaging in fundus albipunctatus with RDH5 mutation: a newly identified compound heterozygous mutation and review of the literature. AB - The aim of this study was to describe multimodal retinal imaging of fundus albipunctatus (FA) with the newly identified compound heterozygous RDH5 mutation and to review the relevant literature. Five family members were examined, and the RDH5 gene was analyzed by direct sequencing. The clinical features and genetic study of FA are reviewed. The proband had a compound heterozygotic missense mutation of Cys59Ser (TGC -> AGC) and a nonsense mutation of Trp95ter (TGG -> TGA) in the RDH5 gene. Fundus examination revealed diffuse yellow flecks with foveal sparing. Infrared reflectance (IR) imaging showed multiple discrete round lesions, and fundus autofluorescence (FAF) imaging showed decreased autofluorescence. In spectral domain optical coherence tomography (SD-OCT), the lesions spanned across the retinal pigment epithelium complex and the photoreceptor inner segment ellipsoid band. The outer nuclear layer thickness is decreased compared to normal control. Electroretinography (ERG) showed improved dark-adapted responses after a prolonged 2.5-h dark adaptation. The fundi of the patient's son and daughter both appeared unremarkable. The clinical findings, differential diagnosis, and genetic studies of these features are reviewed. This is the first time that IR imaging of this disease has been reported; IR imaging showed more detail than did FAF imaging. Although retinal imaging (fundus photographs, FAF, IR, SD-OCT) of FA showed characteristic findings, ERG and genetic study remain the most reliable tests for making the diagnosis. PMID- 22669289 TI - A multiple-ascending-dose study to evaluate safety, pharmacokinetics, and pharmacodynamics of a novel GPR40 agonist, TAK-875, in subjects with type 2 diabetes. AB - G-protein-coupled receptor 40 (GPR40), highly expressed in pancreatic beta-cells, mediates free fatty acid (FFA)-induced insulin secretion. This phase I, double blind, randomized study investigated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of a novel, glucose-lowering GPR40 agonist, TAK 875 (q.d., orally * 14 days), in type 2 diabetics (placebo, n = 14; at 25, 50, 100, 200, or 400 mg, n = 45). Approximately dose-proportional increases in AUC(0 24) and C(max) occurred. TAK-875 showed good tolerability with no dose-limiting side effects. Two subjects (on TAK-875) had mild hypoglycemia, probably related to prolonged fasting after oral glucose tolerance tests (OGTTs). TAK-875 showed reductions from baseline in fasting (2 to -93 mg/dl) and post-OGTT glucose (26 to -172 mg/dl), with an apparent dose-dependent increase in post-OGTT C-peptide over 14 days. Consistent with preclinical data, TAK-875 apparently acts as a glucose dependent insulinotropic agent with low hypoglycemic risk. Its PK is suitable for once-daily oral administration. PMID- 22669290 TI - Physiologically based pharmacokinetic (PBPK) modeling in children. AB - This review summarizes the present status of physiologically based pharmacokinetic (PBPK) modeling and simulation (M&S) and its application in support of pediatric drug research. We address the reasons that PBPK is suited to the current needs of pediatric drug development and pharmacotherapy in light of the evolution in pediatric PBPK methodologies and approaches, which were originally developed for the purpose of toxicologic evaluation. Also discussed is the current degree of confidence in using PBPK to support pediatric drug development and registration and the key factors essential for robust results and broader adoption of pediatric PBPK M&S. PMID- 22669292 TI - Hypoxic-ischemic retinal injury in rat pups. AB - BACKGROUND: Visual loss associated with brain damage, especially hypoxic-ischemic (HI) encephalopathy, is the most common cause of visual impairment in children in developed countries. We hypothesized that HI insults can cause long-term damage in immature eyes. METHODS: In postnatal day 7 rat pups, HI was induced by unilateral common carotid artery ligation followed by hypoxia. Retina damage was assessed by electroretinography (ERG) and cell counting. Neuronal injury and astrogliosis were evaluated by terminal deoxynucleotidyl transferase nick-end labeling, cleaved caspase 3, ED1, and glial fibrillary acidic protein immunostaining. RESULTS: We observed rapid and persistently extensive injuries in the ganglia cell layer (GCL), inner plexiform layer, and inner nuclear layer (INL) in ipsilateral retinas after HI injury, corresponding to the marked alteration in ERG. HI insult caused prominent microglial and Muller cell activation in ipsilateral inner retinas. Neuronal death in the GCL and INL after HI injury was mainly apoptotic, involving caspase-dependent pathways. CONCLUSION: Our study demonstrated the first evidence of HI retinal damage at both the pathological and functional level using the Vannucci model in neonatal rats. Because retinal damage is often associated with HI injury, it is important to demonstrate that a particular neuroprotective strategy effectively preserves the retina in addition to the brain. PMID- 22669291 TI - UGT2B17 genetic polymorphisms dramatically affect the pharmacokinetics of MK-7246 in healthy subjects in a first-in-human study. AB - MK-7246, an antagonist of the chemoattractant receptor on T helper type 2 (Th2) cells, is being developed for the treatment of respiratory diseases. In a first in-human study, we investigated whether genetic polymorphisms contributed to the marked intersubject variability in the pharmacokinetics of MK-7246 and its glucuronide metabolite M3. Results from in vitro enzyme kinetic studies suggested that UGT2B17 is probably the major enzyme responsible for MK-7246 metabolism in both the liver and the intestine. As compared with those with the UGT2B17*1/*1 wild-type genotype, UGT2B17*2/*2 carriers, who possess no UGT2B17 protein, had 25 and 82-fold greater mean dose-normalized values of area under the plasma concentration-time curve (AUC) and peak concentration of MK-7246, respectively, and a 24-fold lower M3-to-MK-7246 AUC ratio. The apparent half-life of MK-7246 was not as variable between these two genotypes. Therefore, the highly variable pharmacokinetics of MK-7246 is attributable primarily to the impact of UGT2B17 genetic polymorphisms and extensive first-pass metabolism of MK-7246. PMID- 22669293 TI - The influence of maternal cortisol and emotional state during pregnancy on fetal intrauterine growth. AB - BACKGROUND: This exploratory study investigates the influence of maternal cortisol and emotional state during pregnancy on fetal intrauterine growth (IUG). We expected higher basal cortisol levels, or more depressive and anxious complaints during pregnancy, to be associated with slower IUG and lower birth weight. METHODS: A total of 91 pregnant women were recruited from the antenatal clinic and were seen once each trimester. In addition to psychological assessments, a diurnal cortisol profile was derived from saliva samples. IUG was evaluated using ultrasound. RESULTS: In mid-pregnancy (trimester (T)2), basal cortisol levels significantly predicted the variance of weight (proportion of variance in growth variable explained (PVE) = 11.6%) and body mass index (BMI) at birth (PVE = 6.8%). In late pregnancy (T3) emotional state, particularly depressive symptoms (BMI at birth: PVE = 6.9%; ponderal index (PI) at birth: PVE = 8.2%; head circumference at T3: PVE = 10.3%; head circumference at birth PVE = 9.1%) and attachment (BMI at birth: PVE = 6.9%; PI at birth: PVE = 7.2%) had an influence on growth. Analysis of growth between T2 and T3 showed that attachment and cortisol in T3 had an influence on the variation in increase in estimated fetal weight (PVE = 12.5-8.6%). CONCLUSION: These data indicate basal cortisol levels were more important in T2 whereas emotional state was more important in T3. PMID- 22669294 TI - Evaluation of air-displacement plethysmography for body composition assessment in preterm infants. AB - BACKGROUND: Adiposity may contribute to the future risk of disease. The aim of this study was to evaluate the accuracy and reliability of an air-displacement plethysmography (ADP) system to estimate percentage fat mass (%FM) in preterm infants and to evaluate interdevice reliability in infants. METHODS: A total of 70 preterm and 9 full-term infants were assessed. The accuracy of ADP measurements was assessed by determining reference %FM values using H(2)(18)O dilution measurement. RESULTS: Mean %FM by ADP was 5.67 +/- 1.84 and mean %FM by H(2)18O dilution was 5.99 +/- 2.56. Regression analysis showed that %FM by ADP was associated with %FM by H(2)(18)O dilution (R2 = 0.63, SE of estimate (SEE) = 1.65, P = 0.006). Bland-Altman analysis showed no bias (r = -0.48, P = 0.16) and 95% limits of agreement were -3.40 to 2.76 %FM. There was no difference in mean interdevice reliability %FM values (8.97 vs. 8.55 %FM) between ADP 1 and 2. Regression analysis indicated a low SEE (1.14% FM) and high R2 (0.91); 95% limits of agreement were -1.87 to 2.71 %FM. The regression line did not differ significantly from the line of identity. CONCLUSION: ADP is a noninvasive, reliable, and accurate technique to measure preterm infants' body composition in both research and clinical settings. PMID- 22669296 TI - Human umbilical cord blood-derived mesenchymal stem cell transplantation attenuates severe brain injury by permanent middle cerebral artery occlusion in newborn rats. AB - BACKGROUND: Severe brain injury induced by neonatal stroke causes significant mortality and disability, and effective therapies are currently lacking. We hypothesized that human umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) can attenuate severe brain injury induced by permanent middle cerebral artery occlusion (MCAO) in rat pups. METHODS: After confirming severe brain injury involving more than 50% of the ipsilateral hemisphere volume at 1 h after MCAO using diffusion-weighted magnetic resonance imaging (MRI) in postnatal day (P)10 rats, human UCB-derived MSCs were transplanted intraventricularly. The brain MRI was evaluated periodically up to 28 d after MCAO (P38). Sensorimotor function and histology in the peri-infarct tissues were evaluated at the end of the experiment. RESULTS: Severe brain injury induced by permanent MCAO resulted in decreased survival and body weight gain, increased brain infarct volume as measured by MRI, impaired functional tests such as the rotarod and cylinder test, and histologic abnormalities such as increased terminal deoxynucleotidyl transferase nick-end labeling, reactive microglial marker, and glial fibrillary acidic protein-positive cells in the penumbra. All of these abnormalities were significantly improved by MSC transplantation 6 h after MCAO. CONCLUSION: These results suggest that human UCB-derived MSCs are a promising therapeutic candidate for the treatment of severe perinatal brain injury including neonatal stroke. PMID- 22669297 TI - Continuous renal replacement therapy to reduce inflammation in a piglet hemorrhage-reperfusion extracorporeal membrane oxygenation model. AB - BACKGROUND: During extracorporeal membrane oxygenation (ECMO), circulation of blood across synthetic surfaces triggers an inflammatory response. Therefore, we evaluated the ability of continuous renal replacement therapy (CRRT) to remove cytokines and reduce the inflammatory response in a piglet hemorrhage-reperfusion ECMO model. METHODS: Three groups were studied: (i) uninjured controls (n = 11); (ii) hemorrhage-reperfusion while on venoarterial ECMO (30% hemorrhage with subsequent blood volume replacement within 60 min) (n = 8); (iii) treatment with CRRT after hemorrhage-reperfusion while on ECMO (n = 7). Hemodynamic parameters, oxygen utilization, and plasma and broncho-alveolar lavage (BAL) cytokine levels were recorded and lung tissue samples collected for histologic comparison. RESULTS: Whereas mean arterial pressures decreased among hemorrhage-reperfusion piglets, ECMO with CRRT did not significantly alter mean arterial pressures or systemic vascular resistance and was able to maintain blood flow as well as oxygen delivery after hemorrhage-reperfusion. Plasma interleukin (IL)-6 and IL 10, and BAL tumor necrosis factor (TNF)-alpha, IL-1beta, IL-6, IL-8, and IL-10 increased as a result of hemorrhage-reperfusion while on ECMO. After a 6-h period of CRRT, plasma IL-6 and BAL TNF-alpha, IL-6, and IL-8 levels decreased. CONCLUSION: Data suggest CRRT may decrease inflammatory cytokine levels during the initial phase of ECMO therapy following hemorrhage-reperfusion while maintaining cardiac output and oxygen utilization. PMID- 22669298 TI - Sleep fragmentation and intermittent hypoxemia are associated with decreased insulin sensitivity in obese adolescent Latino males. AB - BACKGROUND: Although sleep-related breathing disorder (SRBD) has been linked to insulin resistance in adults, this has not been as well established in children. We hypothesized that the severity of SRBD in adolescents was associated with metabolic impairment. METHODS: Polysomnography was performed on obese, Latino males referred for snoring. The frequently sampled intravenous glucose tolerance test was used to assess glucose homeostasis. Total-body dual-energy X-ray absorptiometry was used to quantify adiposity. RESULTS: A total of 22 males (mean age +/- SD: 13.4 +/- 2.1 y, BMI z-score 2.4 +/- 0.3, obstructive apnea hypopnea index 4.1 +/- 3.2) were studied. After correcting for age and adiposity in multiple-regression models, Log frequency of desaturation (defined as >=3% drop in oxygen saturation from baseline) negatively correlated with insulin sensitivity. Sleep efficiency was positively correlated with glucose effectiveness (S(G), the capacity of glucose to mediate its own disposal). The Log total arousal index was positively correlated with Log homeostasis model assessment-estimated insulin resistance. CONCLUSION: Sleep fragmentation and intermittent hypoxemia are associated with metabolic impairment in obese adolescent Latino males independent of age and adiposity. We speculate that SRBD potentiates the risk for development of metabolic syndrome and type 2 diabetes in the obese adolescent population. PMID- 22669299 TI - Estimating the division rate for the growth-fragmentation equation. AB - Growth-fragmentation equations arise in many different contexts, ranging from cell division, protein polymerization, neurosciences etc. Direct observation of temporal dynamics being often difficult, it is of main interest to develop theoretical and numerical methods to recover reaction rates and parameters of the equation from indirect observation of the solution. Following the work done in Perthame and Zubelli (Inverse Probl 23:1037-1052, 2007) and Doumic et al. (2009) for the specific case of the cell division equation, we address here the general question of recovering the fragmentation rate of the equation from the observation of the time-asymptotic solution, when the fragmentation kernel and the growth rates are fully general. We give both theoretical results and numerical methods, and discuss the remaining issues. PMID- 22669300 TI - A genetic linkage map of Brassica carinata constructed with a doubled haploid population. AB - Brassica carinata is an important oilseed crop with unique favourable traits that are desirable for other Brassica crops. However, given the limited research into genetic resources in B. carinata, knowledge of the genetic structure of this species is relatively poor. Nine homozygous, genetically distinct accessions of B. carinata were obtained via microspore culture, from which two divergent doubled haploid (DH) lines were used to develop a DH mapping population that consisted of 183 lines. The mapping population showed segregation of multiple traits of interest. A genetic map was constructed with PCR-based markers, and a total of 212 loci, which covered 1,703 cM, were assigned to eight linkage groups in the B genome and nine linkage groups in the C genome, which allowed comparison with genetic maps of other important Brassica species that contain the B/C genome(s). Loci for two Mendelian-inherited traits related to pigmentation (petal and anther tip colour) and one quantitative trait (seed coat colour) were identified using the linkage map. The significance of the mapping population in the context of genetic improvement of Brassica crops is discussed. PMID- 22669301 TI - Characterization of QTL for oil content in maize kernel. AB - Kernel oil content in maize is a complex quantitative trait. Phenotypic variation in kernel oil content can be dissected into its component traits such as oil metabolism and physical characteristics of the kernel, including embryo size and embryo-to-endosperm weight ratio (EEWR). To characterize quantitative trait loci (QTL) for kernel oil content, a recombinant inbred population derived from a cross between normal line B73 and high-oil line By804 was genotyped using 228 molecular markers and phenotyped for kernel oil content and its component traits [embryo oil content, embryo oil concentration, EEWR, embryo volume, embryo width, embryo length, and embryo width-to-length ratio (EWLR)]. A total of 58 QTL were identified for kernel oil content and its component traits in 26 genomic regions across all chromosomes. Eight main-effect QTL were identified for kernel oil content, embryo oil content, embryo oil concentration, EEWR, embryo weight, and EWLR, each accounting for over 10 % of the phenotypic variation in six genomic regions. Over 90 % of QTL identified for kernel oil content co-localized with QTL for component traits, validating their molecular contribution to kernel oil content. On chromosome 1, the QTL that had the largest effect on kernel oil content (qKO1-1) was associated with embryo width; on chromosome 9, the QTL for kernel oil content (qKO9) was related to EEWR (qEEWR9). Embryo oil concentration and embryo width were identified as the most important component traits controlling the second largest QTL for kernel oil content on chromosome 6 (qKO6) and a minor QTL for kernel oil content on chromosome 5 (qKO5-2), respectively. The dissection of kernel oil QTL will facilitate future cloning and/or functional validation of kernel oil content, and help to elucidate the genetic basis of kernel oil content in maize. PMID- 22669302 TI - Lack of circulating pigment epithelium-derived factor is a marker of osteogenesis imperfecta type VI. AB - BACKGROUND: Osteogenesis imperfecta (OI) type VI is a rare autosomal recessive bone fragility disorder that is caused by inactivating mutations in SERPINF1, the gene that encodes pigment-epithelium derived factor (PEDF). Determining PEDF serum levels might facilitate the diagnosis of OI type VI. OBJECTIVE: The objective of the study was to assess whether lack of circulating PEDF is a specific marker of OI type VI and to evaluate whether PEDF serum levels are influenced by other metabolic bone diseases. MATERIALS AND METHODS: Serum PEDF concentrations were measured in 12 patients with OI type VI (aged 2.7-31 yr) as well as in 96 children and adolescents with OI types I, III, and IV; in 26 young patients with hypophosphatemic rickets; and in 19 healthy controls. RESULTS: Circulating PEDF was undetectable in all 12 patients with OI type VI but was measurable for the other 141 study participants. No significant differences in serum PEDF concentrations were found between the diagnostic groups other than OI type VI. Treatment with bisphosphonates (in OI types I, III, and IV) and with phosphate and calcitriol (in hypophosphatemic rickets) did not have a detectable influence on serum PEDF. In patients with OI types I, III, and IV, serum creatinine, body mass index z-score, and OI severity were significant predictors of PEDF serum levels. CONCLUSION: Determining PEDF serum concentration helps to diagnose OI type VI but does not seem to provide information on the activity of bone turnover or mineralization. PMID- 22669303 TI - Management of postmenopausal virilization. AB - CONTEXT: Mild clinical signs of hyperandrogenism such as hirsutism may appear during the menopausal transition as part of the normal aging process, but the development of frank virilization suggests a specific source of androgen excess, including androgen-secreting tumors. PATIENT AND METHODS: A 68-yr-old postmenopausal woman was referred because of a history of progressive development of hirsutism and frontal balding for the previous 8 yr, together with moderate hyperandrogenemia. Initial imaging procedures depicted a 2-cm solid nodule in the right adrenal gland and normal appearance of both ovaries. To confirm the source of androgen excess, we conducted simultaneous selective venous sampling of adrenals and ovaries. Sampling was consistent with an ovarian source. After bilateral laparoscopic salpingo-oophorectomy, the patient was diagnosed with bilateral ovarian hyperthecosis. Three weeks after surgery, her androgen levels had decreased to the normal female range. CONCLUSION: Diagnosis of hyperandrogenism in postmenopausal women is challenging. Postmenopausal virilization may be associated with adrenal or ovarian androgen-secreting tumors or with benign conditions. A detailed clinical history is critical to differentiate the progressive development of virilization that characterizes benign causes from the rapid progression that characterizes malignant tumors. Imaging techniques do not always reveal the cause of hyperandrogenism and may even be misleading. Although technically difficult, combined adrenal and ovarian venous sampling may be required to confirm the source of androgen excess before the best surgical approach is determined. PMID- 22669304 TI - Thyroid dysfunction during late gestation is associated with excessive iodine intake in pregnant women. AB - CONTEXT: Adequate iodine intake during pregnancy is essential for both the synthesis of maternal thyroid hormones and the maintenance of normal fetal brain development. Scant evidence is available on the effects of excessive iodine intake during pregnancy. OBJECTIVE: The study assesses the relationship between iodine nutritional status and thyroid function of pregnant women with excessive iodine intake during late gestation. DESIGN AND PARTICIPANTS: A cross-sectional study of 384 pregnant women was carried out in Tianjin and Haixing from April to October in 2010. MAIN OUTCOME MEASURES: Morning urine samples and blood samples were obtained from all subjects. Serum levels of free T(3), free T(4), and sensitive TSH and urinary iodine concentration were measured. RESULTS: The median urinary iodine concentration of pregnant women with excessive iodine intake was significantly higher than those with adequate iodine intake (P < 0.001). The prevalence of thyroid disease, especially subclinical hypothyroidism, in pregnant women with excessive iodine intake was significantly higher than in those with adequate iodine intake (P < 0.05). Subclinical hypothyroidism was the most frequent pattern of thyroid disease for pregnant women and those with positive or negative thyroid autoantibodies. Living with high water iodine content and having urinary iodine concentration higher than 250 MUg/liter are associated risk factors for subclinical hypothyroidism in pregnant women (OR(1) = 41.822, OR(2) = 6.202; P < 0.05, where OR(1) is the odds ratio for living with high water iodine content and hypothyroidism and OR(2) is the odds ratio for urinary iodine concentration >250 MUg/liter and hypothyroidism). CONCLUSIONS: Excessive iodine intake during late pregnancy may lead to maternal thyroid dysfunction, particularly subclinical hypothyroidism. The appropriate measurements should be performed to monitor the onset of hypothyroidism in pregnant women with excessive iodine intake. PMID- 22669305 TI - An overview of UV-absorbing compounds (organic UV filters) in aquatic biota. AB - The purpose of this article is to summarize biological monitoring information on UV-absorbing compounds, commonly referred as organic UV filters or sunscreen agents, in aquatic ecosystems. To date a limited range of species (macroinvertebrates, fish, and birds), habitats (lakes, rivers, and sea), and compounds (benzophenones and camphors) have been investigated. As a consequence there is not enough data enabling reliable understanding of the global distribution and effect of UV filters on ecosystems. Both liquid chromatography and gas chromatography coupled with mass spectrometry-based methods have been developed and applied to the trace analysis of these pollutants in biota, enabling the required selectivity and sensitivity. As expected, the most lipophilic compounds occur most frequently with concentrations up to 7112 ng g( 1) lipids in mussels and 3100 ng g(-1) lipids (homosalate) in fish. High concentrations have also been reported for 4-methylbenzilidenecamphor (up to 1800 ng g(-1) lipids) and octocrylene (2400 ng g(-1) lipids). Many fewer studies have evaluated the potential bioaccumulation and biomagnification of these compounds in both fresh and marine water and terrestrial food webs. Estimated biomagnification factors suggest biomagnification in predator-prey pairs, for example bird-fish and fish-invertebrates. Ecotoxicological data and preliminary environmental assessment of the risk of UV filters are also included and discussed. PMID- 22669306 TI - A new method for quantifying prenatal exposure to ethanol by microwave-assisted extraction (MAE) of meconium followed by gas chromatography-mass spectrometry (GC MS). AB - Ethanol is a legal and widely available substance. There are health and social consequences associated with its abuse. One of the most important problems is related to alcohol consumption during pregnancy. In fact, prenatal ethanol exposure can be associated with fetal alcohol spectrum disorder (FASD), a term used to describe a wide range of potentially lifelong effects that include physical, mental, behavioral, and learning disabilities. Fatty acid ethyl esters (FAEEs), which are non-oxidative metabolites of ethanol, are currently used as biomarkers of direct ethanol consumption in different matrices, including hair, blood, skin surface, and meconium. Analysis of these compounds in meconium reveals exposure to alcohol during the second and third trimesters of pregnancy. An important finding for evaluation of gestational ethanol exposure is the fact that FAEEs do not cross the placenta. Because they accumulate in the fetal gut from approximately the 20th week of gestation until birth, this provides a wide window of detection of chronic exposure to alcohol. The sum of the concentrations of all the FAEEs, with a cutoff of 2 nmol g(-1) or 600 ng g(-1) meconium, has been recommended as evidence of maternal alcohol use. We introduce a novel technique to quantify ethyl myristate, ethyl palmitate, ethyl stearate, and their deuterated analogues (as internal standards, IS) in meconium using microwave assisted extraction (MAE) coupled with gas chromatography-mass spectrometry (GC MS). Limits of detection and quantification were 50 and 100 ng g(-1) for all analytes except ethyl stearate (LOD 100 ng g(-1) and LOQ 500 ng g(-1)). Calibration curves were linear from the LOQ to 5000 ng g(-1). The validated method was applied to the analysis of 81 meconium samples. PMID- 22669307 TI - Mercury speciation analysis in human hair by species-specific isotope-dilution using GC-ICP-MS. AB - We optimized a mercury (Hg) speciation extraction method for human hair in combination with species-specific isotope-dilution analysis by gas chromatography inductively coupled plasma-mass spectrometry (GC-ICP-MS). The method was validated on human hair reference material RM (IAEA-086), which is recommended for analysis of monomethylmercury (MMHg) and inorganic mercury (IHg). Three reagents, hydrochloric acid (HCl), nitric acid (HNO3), and tetramethylammonium hydroxide (TMAH), and three extraction procedures, at ambient temperature for 12 h, microwave-assisted at 75 degrees C for 6 min, and oven heated at 80 degrees C for 2 h were tested. Extraction efficiency, recovery, and potential species transformations were evaluated for each method. The most efficient procedures, with recovery of ~90 % for each species with limited demethylation (<5 %) and methylation (0 %), were HNO3 digestion, irrespective of temperature, and microwave-assisted TMAH extraction. Acidic extraction with HCl induces significant demethylation, with production of artifacts. To correct for potential demethylation artifacts we recommend spiking with isotopically enriched standards before the extraction step. PMID- 22669308 TI - Rapid narrow band elution for on-line SPE using a novel solvent plug injection technique. AB - Determination of trace constituents in biological and environmental samples usually requires a pre-concentration step. While solid-phase extraction (SPE) has been widely used, it is slow, labor intensive and adversely affected by analytical errors from handling. On-line SPE eliminates some of the flaws but often suffers from solvent compatibility problems with the subsequent chromatography separation. In this study, we are presenting a technical solution for overcoming some of these compatibility issues, by utilizing a fully automated, focused SPE sample transfer technique utilizing narrow-band solvent plugs, for seamless hyphenation with high-performance liquid chromatography (HPLC) or flow injection mass spectrometry (MS). A wide range of pharmaceutical compounds was studied in different sample matrices. Short plugs of high elution strength solvent were generated by means of an electrically actuated sample loop and enrichment and transfer steps monitored using on-line SPE-MS. The impact of the solvent plugs on chromatographic separation was studied using hyphenated SPE LC-MS. By carefully examining elution profiles of solvent plugs of different compositions, optimum conditions for quantitative elution within well-defined volumes were found for all substances. In addition, the highly focused elution bands resulted in excellent retention time and peak area reproducibilities when injected on-line onto HPLC columns. Finally, to demonstrate proof-of-principle, the fully integrated on-line SPE-LC-MS system was applied to the analysis of spiked urine and river water samples. PMID- 22669309 TI - [Sudden cardiac death and automated external defibrillators. Where we are in 2012?]. AB - Sudden cardiac death (SCD) is one of the major problems in the western world with approximately 70.000-100.000 SCD patients (pts) in Germany and 450.000 SCD victims in the US. SCD is not caused by a single factor but is a multifactorial problem. SCD is caused by ventricular tachyarrhythmias in approximately 90% of pts, whereas SCD is caused by bradyarrhythmias in 5-10%. In 50% of SCD victims, sudden cardiac death is the first manifestation of a heart disease. There is general agreement that early defibrillation with automated external defibrillators (AED) is an effective tool to treat pts with ventricular fibrillation. Nevertheless, further stragies on cardiopulmonary resuscitation and AED therapy are necessary to improve survival of patients with cardiac arrest. PMID- 22669310 TI - Big endothelin-1 as a predictor of atrial fibrillation recurrence after primary ablation only in patients with paroxysmal atrial fibrillation. AB - BACKGROUND: Atrial fibrillation (AF) recurrence after ablation is difficult to predict. The development of AF is associated with inflammation, and inflammatory markers such as big endothelin-1 (big ET-1) reflect inflammatory status. It is unknown, however, whether big ET-1 can be used as a predictor for AF recurrence. The aim of this study was to investigate the relationship between plasma levels of big ET-1 and AF recurrence. METHODS: A total of 158 patients who had undergone primary ablation for symptomatic and/or drug-refractory AF, including 103 with paroxysmal and 55 with persistent AF, were included in this study. Left atrial diameter was measured with echocardiography and plasma big ET-1 levels with ELISA. All patients were followed up for at least 12 months and AF recurrence defined as an episode of AF lasting >= 30 s, with or without atrial flutter or atrial tachycardia. RESULTS: The AF recurrence rate was 44.9% (71/158) during the median follow-up period of 22 (13, 40) months. Plasma levels of big ET-1 in the recurrence group were higher than those in the non-recurrence group in all patients [0.80 (0.54, 1.30) vs. 0.57 (0.48, 0.72) fmol.L(-) (1), p = 0.001], in patients with paroxysmal AF [0.81 (0.46, 1.30) vs. 0.57 (0.48, 0.70) fmol.L(-) (1), p = 0.009] as well as in patients with persistent AF [0.77 (0.57, 1.28) vs. 0.57 (0.49, 0.89) fmol.L(-) (1), p = 0.034]. Multiple logistic regression analyses showed that plasma levels of big ET-1 were associated with AF recurrence in patients with paroxysmal AF (p = 0.037). Kaplan-Meier analysis demonstrated that the sinus rhythm maintenance rate was lower in patients with higher big ET-1 levels than those with lower levels (p < 0.05). CONCLUSIONS: Baseline plasma big ET-1 levels are associated with AF recurrence after primary ablation procedure in patients with paroxysmal AF, and may be used in the prediction of AF recurrence in these patients. PMID- 22669311 TI - [Anticoagulation. Start of a new era?]. PMID- 22669313 TI - Rare hepatic malignant tumors: dynamic CT, MRI, and clinicopathologic features: with analysis of 54 cases and review of the literature. AB - AIM: To evaluate the dynamic CT, MRI, and clinicopathologic characteristics of rare hepatic malignant tumors (HRMTs), improving the understanding and diagnosis of the tumors. METHODS: A retrospective analysis of 54 cases of HRMTs diagnosed by pathology in our hospital during January 1, 2005 to September 1, 2011. RESULTS: The types of tumors included hepatic sarcoma (n = 8), malignant lymphoma (n = 4), malignant fibrous histiocytoma (MFH, n = 7), malignant melanoma (MM, n = 4), squamous cell carcinoma (SCC, n = 5), primary clear cell carcinoma of the liver (PCCCL, n = 7), stromal tumors (ST n = 4), hepatoblastoma (HB, n = 8), carcinoid (n = 6), primary primitive neuroectodermal tumor (pPNET, n = 1). Age of the patients ranged from 1 to 79 years (mean = 46.7 years). There were more men in this group (34/54). Symptoms of HRMTs show no specificity. Except PCCCL and HB, the serum AFP of most HRMTs was negative. 43 patients had a single hepatic mass, and 11 patients had multiple hepatic masses. Diameters ranged from 2 to 15 cm (mean = 7.7 cm). Precontrast CT revealed that most masses had uneven density (n = 46) and ill-demarcated margin (n = 37). Enhanced CT showed most lesions unevenly enhanced (n = 49), of which PCCCL had a prompt enhancement in the arterial phase and rapid wash-out on the portal venous phase and delayed phase; malignant lymphoma and ST had slight enhancement, MFH and undifferentiated embryonal sarcoma had gradual delayed enhancement. Most masses had low-signal on T1WI and high-signal on T2WI, while MM had high-signal on T1WI and low-signal on T2WI. CONCLUSIONS: Although there is frequent overlap in the CT, MRI, and clinicopathologic appearances between the rare malignant tumors, some HRMTs have characteristic imaging features that can suggest a specific diagnosis. PMID- 22669312 TI - [Aerobic and strength training in patients with diabetes mellitus type 2 and heart failure]. AB - Patients with type 2 diabetes mellitus and heart failure represent a relevant population in everyday practice. Several exercise training studies have documented numerous positive changes in cardiovascular risk factors, morbidity and mortality, that can only be achieved through long-term training programs of combined aerobic and strength training. This efficient and cost effective therapy should be offered to as many patients in need as possible. PMID- 22669314 TI - [Dentogenic infections-part I: the significance of bacterial isolation of dentogenic infections under routineous conditions]. AB - The microflora of odontogenic infections is typically polymicrobial with increased resistance rates against various antibiotics. The purpose of the present study was to analyze bacterial spectra and resistance in odontogenic infections under routineous conditions.Microbiological samples were collected and transported under routineous conditions in a prospective study of 19 patients. All Bacterial spectra and resistance rates were compared with the results of a former prospective evaluation.There were 11 men, 5 woman and 3 children (age range of 2-86 years). A total of only 38 bacterial strains were analyzed. The ratio between aerobes and anaerobes was nearly 1:1. The resistance rates were nearly the same for Penicillin G, but a 2-fold increased resistance for clindamycin against aerobes and a more than 10-fold increased resistance against anaerobes was noted.Prospective studies under standardized conditions are necessary to isolate strict anaerobes and to detect changes in antibiotic efficiency. PMID- 22669315 TI - A new class of PANI-Ag core-shell nanorods with sensing dimensions. AB - A single-step, cost-effective and eco-safe synthesis of a new class of homogeneous silver-polyaniline (PANI-Ag) core-shell nanorods is carried out via mild photolysis by ultraviolet radiation from sunlight (SUN UV-radiation). X-ray diffraction (XRD) of these core-shell nanorods gives two additional peaks from PANI centered at 2theta = 20.5 degrees and 24. 9 degrees . A validation of the core-shell structural information is given by transmission electron spectroscopy (TEM) whereas the tubular shape morphology is determined by scanning electron microscopy (SEM). UV-Vis. absorption shows a strong blue-shift along with photoluminescence emission. Fourier transform-infrared spectroscopy (FT-IR) and energy dispersive X-ray spectroscopy (EDX) also support the core-shell formation. Thermogravimetric analysis (TGA) shows good thermal stability and allows excellent detection of hydrogen peroxide and hydrazine. The cyclic voltammetry (CV) results show excellent electro-activation, indicating its promising potential in sensing of clinical and environmental analytes. PMID- 22669316 TI - Molecular epidemiological study of hepatitis B virus in blood donors from five Chinese blood centers. AB - Although the genetic variability of hepatitis B virus (HBV) in HBV-infected patients has been extensively studied, reports on genotypes, subtypes and mutations in the S region of HBV strains from Chinese blood donors are limited. In this study, 245 blood samples from HBsAg-positive blood donors were collected from five geographically diverse blood centers in China. The S region of HBV was amplified, and the HBV genotype and subtype were determined. The amino acid sequences of the S region were aligned, and mutations related to the failure of immunization and HBsAg detection were determined. Of the 245 samples, 228 (93 %) were genotyped successfully. We found that genotypes B, C, D and A accounted for 58.8 %, 21.9 %, 6.6 % and 3.95 % of the isolates, respectively. The distribution of HBV antigen subtypes was as follows: adw (67.6 %), adr (23.3 %) and ayw (8.7 %). Mutations were present in 39 (17.1 %) of 228 samples in the major hydrophilic region (MHR) of the S region. This study demonstrated that HBV genotype/subtype B/adw was the most frequent strain circulating in HBV-infected Chinese blood donors, followed by C/adr. The occurrence of MHR mutants in HBV-infected blood donors and the potential failure to detect some of them in collected units poses a threat to transfusion safety. PMID- 22669318 TI - Characterization of malleability and immunological properties of human adenovirus type 3 hexon hypervariable region 1. AB - Adenovirus (Ad) capsids that display exogenous epitopes can be potently immunogenic, eliciting a potent humoral response against components of the capsid. We used the epitopes flag, his(6)flag, his(6)lgsflag and AdV4HVR5 as model antigens to characterize the hexon hypervariable region (HVR) 1 as a site for epitope insertion. A peptide of up to 17 amino acids could be incorporated into HVR1 of the Ad3 hexon without adversely affecting the biological characteristics of the virus. Multiple vaccinations with capsid-modified Ad3 induced a humoral response against the epitope inserted in HVR1. However, antiserum against the his(6)flag or his(6)lgsflag epitope did not recognize glutathione S-transferase (GST)-his(6) and GST-flag fusion protein. Our study illustrates that there is an immune response against the new epitope within the amino acids of his(6)flag or his(6)lgsflag epitopes. This discovery could be a warning for the generation of multivalent vaccine vectors by incorporation of multiple epitopes into single HVRs. PMID- 22669317 TI - The immune response to Nipah virus infection. AB - Nipah virus has recently emerged as a zoonotic agent that is highly pathogenic in humans. Outbreaks have occurred regularly over the last two decades in South and Southeast Asia, where mortality rates reach as high as 100 %. The natural reservoir of Nipah virus has been identified as bats from the Pteropus family, where infection is largely asymptomatic. Human disease is characterized by both respiratory and encephalitic components, and thus far, no effective vaccine or intervention strategies are available. Little is know about how the immune response of either the reservoir host or incidental hosts responds to infection, and how this immune response is either inadequate or might contribute to disease in the dead-end host. Experimental vaccines strategies have given us some insight into the immunological requirements for protection. This review summarizes our current understanding of the immune response to Nipah virus infection and emphasizes the need for further research. PMID- 22669319 TI - Novel C3 mutation p.Lys65Gln in aHUS affects complement factor H binding. AB - BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is associated with mutations affecting complement proteins and regulators and with autoantibodies against complement factor H (CFH). Approximately half of the aHUS patients progress to end-stage renal disease. DNA analysis of the risk factor genes is important for prognosis of aHUS recurrence after renal transplantation. METHODS: Mutational screening of C3 encoding the central complement component was performed by Sanger sequencing in 70 aHUS patients. Mutated and wild type recombinant C3b proteins were produced and their affinity to CFH was analyzed by ELISA. RESULTS: A single novel missense change p.Lys65Gln in C3 was found in 3 aHUS patients. The alteration leads to decreased binding of C3b to CFH in vitro. All three patients acquired the illness as adults and had a first aHUS episode after renal transplantation or suffered recurrence of the disease after transplantation. CONCLUSIONS: The novel C3 change was found in 3 aHUS patients. It results in decreased C3b binding to CFH and thus might lead to impaired C3b inactivation in vivo. The p.Lys65Gln is likely to be associated with aHUS after kidney transplantation and, therefore, might be an important prognostic factor. PMID- 22669320 TI - The effect of a multidisciplinary care clinic on the outcomes in pediatric chronic kidney disease. AB - BACKGROUND: Current best evidence-based practice for children with chronic kidney disease (CKD) attempts to achieve good clinical outcomes through careful management of comorbidities and is likely best achieved with a multidisciplinary care (MDC) CKD clinic. METHODS: In this retrospective study of children with CKD in British Columbia, Canada, we analyzed clinical outcomes in a cohort of 73 CKD patients from 2003 under a standard care model and a second cohort of 125 CKD patients from 2009 under a MDC clinic model. RESULTS: Patient demographics were similar, but there was a decrease in the percentage of patients with CKD stage 3 5 in 2009 (59 vs. 75 %; p = 0.002), although the absolute number increased. After adjustment for severity of CKD, hemoglobin was significantly higher (13.0 g/dl vs. 12.2 g/dl, p < 0.03), calcium was significantly higher (9.6 mg/dl vs. 9.1 mg/dl, p < 0.001), and albumin was significantly higher (4.4 g/dl vs. 3.8 g/dl, p < 0.001) in the 2009 MDC cohort. The rate of disease progression, assessed by annualized estimated glomerular filtration rate (eGFR) slope, improved from -4.0 ml/min/1.73 m(2) in the 2003 cohort to 0.5 ml/min/1.73 m(2) in the 2009 cohort (p < 0.01). Blood pressure control was better in 2009 although not statistically significant. CONCLUSIONS: Multidisciplinary care improved the outcomes of children with CKD especially in anemia management, bone mineral metabolism, nutrition, and renal disease progression. PMID- 22669321 TI - Membrano-proliferative glomerulonephritis, atypical hemolytic uremic syndrome, and a new complement factor H mutation: report of a case. AB - BACKGROUND: Complement protein factor H (CFH) is a regulatory protein of the alternative complement pathway (AP); CFH mutations lead to a spectrum of different phenotypical manifestations of renal disease. CASE-DIAGNOSIS/TREATMENT: We report the case of a boy with a novel CFH gene mutation who presented with a membranoproliferative (MPGN) pattern of glomerular injury and developed 2 years later atypical hemolytic uremic syndrome (aHUS); this description shows that CFH alteration leads to two different renal diseases in the same patient. CONCLUSIONS: Our case suggests the possibility that complement dysregulation could determine different renal conditions, which may be part of the same disease spectrum. Early recognition of an evolution of glomerulopathies into aHUS may allow appropriate management and prevention of life-threatening consequences. PMID- 22669322 TI - Obesity in patients with Bardet-Biedl syndrome: influence of appetite-regulating hormones. AB - BACKGROUND: Bardet-Biedl syndrome (BBS) is a genetic disorder with obesity as one of the major phenotypic criterion, which is proposed to be of neuroendocrine origin. Therefore, disturbances in appetite-regulating hormones have been considered as causative factors. Acyl ghrelin is an orexigenic hormone, whereas its desacylated form, obestatin, and leptin have the opposite functions. Ghrelin is negatively regulated in relation to nutritional status. The aim of this study was to evaluate the impact of hormone alterations on obesity development in BBS patients. METHODS: Total and acylated ghrelin, obestatin, leptin and adiponectin were measured in eight children with BBS. The results were analyzed in relation to auxological parameters [body mass index (BMI), height]. RESULTS: The mean BMI was significantly increased in BBS patients compared to the controls. Plasma levels of acylated ghrelin, total ghrelin and obestatin were slightly elevated in BBS patients compared to controls, as was the acyl/total ghrelin ratio. Leptin levels were significantly elevated in BBS patients. CONCLUSION: BBS patients lack the negative regulatory mechanisms of appetite-regulating hormones with respect to nutritional status and exhibit resistance to anorexigenic leptin. This results in a shift towards the orexigenic effects of this self-regulating system. These alterations may in part be responsible for the disturbed appetite regulation in BBS patients. PMID- 22669323 TI - Y chromosome interstitial deletion induced Y-STR allele dropout in AMELY-negative individuals. AB - Short tandem repeat (STR) multiplexes with the amelogenin (AMEL) gene as a gender marker have been used as a routine tool of forensic DNA analysis. It has been reported that AMEL-based gender detection could misidentify a known male as a female due to the dropout of amelogenin Y (AMELY) allele. Other gender markers, such as Y-chromosomal short tandem repeat (Y-STR), may be a substitution of AMEL and help the sex determination. In current study, employing AmpFlSTR(r) Sinofiler and AmpFlSTR(r) Y-filerTM PCR Amplification kit, 18 AMELY-negative males were identified. Accordingly, the incidence of the AMELY dropout was 0.227 0/00 (18/79,304) in Chinese population. Sequencing of AMELY allele and analyzing of azoospermia factors region suggested that 3 out of 18 misidentifications were induced by mutations in the primer-binding region of the AMELY, while other 15 sex misidentifications were results of Y chromosome microdeletions with variant lengths. Moreover, variant combination patterns of AMELY dropout and Y-STRs deletions were also observed. Our data suggested that Y-STR locus dropout may indicate more problems, especially in the mixed sample's interpretation. Results of haplogroup prediction showed that seven AMELY dropouts combined with variant Y STR deletions can be classified as the J2 subdivision, suggesting that some of these Y chromosomes might descend from a common ancestor. PMID- 22669325 TI - Is acute subdural hematoma reduced during the agonal stage and postmortem? AB - The issue of proper use of postmortem computed tomography (PMCT) in forensic fields is currently being actively discussed. The PMCT image has specific findings that differ from the antemortem image, and it is essential to understand and interpret postmortem changes in order to utilize PMCT properly. In this article, we present two cases of acute subdural hematoma (ASDH) in which images were obtained both ante- and postmortem. These images showed marked reduction of hematoma and diminishing midline shift between the agonal and postmortem periods, without evacuation of the hematoma. Attention should be paid to this phenomenon because key findings in determining cause of death could disappear if investigating the cause of death takes too long in cases that prove to be ASDH. In other words, this phenomenon potentially becomes a risk for misdiagnosis when we decide the cause of death without knowing the details of the circumstances of death. PMID- 22669324 TI - Hyperthermia and postmortem biochemical investigations. AB - The postmortem diagnosis of heat-related deaths presents certain difficulties. Firstly, preterminal or terminal body temperatures are often not available. Additionally, macroscopic and microscopic findings are nonspecific or inconclusive and depend on survival duration after exposure. The diagnosis of hyperthermia is therefore essentially based on scene investigation, the circumstances of death, and the reasonable exclusion of other causes of death. Immunohistochemistry and postmortem biochemical investigations have been performed by several authors in order to better circumstantiate the physiopathology of hyperthermia and provide further information to confirm or exclude a heat-related cause of death. Biochemical markers, such as electrolytes, hormones, blood proteins, enzymes, and neurotransmitters, have been analyzed in blood and other biological fluids to improve the diagnostic potential of autopsy, histology, and immunohistochemistry. The aim of this article is to present a review of the medicolegal literature pertaining to the postmortem biochemical investigations that are associated with heat-related deaths. PMID- 22669327 TI - Aluminum complexes of the redox-active [ONO] pincer ligand. AB - A series of aluminum complexes containing the tridentate, redox-active ligand bis(3,5-di-tert-butyl-2-phenol)amine ([ONO]H(3)) in three different oxidation states were synthesized. The aluminum halide salts AlCl(3) and AlBr(3) were reacted with the doubly deprotonated form of the ligand to afford five-coordinate [ONHO(cat)]AlX(solv) complexes (1a, X = Cl, solv = OEt(2); 1b, X = Br, solv = THF), each having a trigonal bipyramidal coordination geometry at the aluminum and containing the [ONHO(cat)](2-) ligand with a protonated, sp(3)-hybridized nitrogen donor. The [ONO] ligand platform may also be added to aluminum through the use of the oxidized ligand salt [ONO(q)]K, which was reacted with AlCl(3) in the presence of either diphenylacetylacetonate (acacPh(2)(-)) or 8-oxyquinoline (quinO(-)) to afford [ONO(q)]Al(acacPh(2))Cl (2) or [ONO(q)]Al(quinO)Cl (3), respectively, with well-defined [ONO(q)](-) ligands. Quinonate complexes 2 and 3 were reduced by one electron to afford the corresponding complexes K{[ONO(sq)]Al(acacPh(2))(py)} (4) and K{[ONO(sq)]Al(quinO)(py)} (5), respectively, containing well-defined [ONO(sq)](2-) ligands. The addition of tetrachloro-1,2-quinone to 1a in the presence of pyridine resulted in the expulsion of HCl and the formation of an aluminum complex with two different redox active ligands, [ONO]Al(o-O(2)C(6)Cl(4))(py) (6). Similar results were obtained when 1a was reacted with 9,10-phenanthrenequinone to afford [ONO]Al(o O(2)C(14)H(8))(py) (7) or with pyrene-4,5-dione to afford [ONO]Al(o O(2)C(16)H(8))(py) (8). Structural, spectroscopic and preliminary magnetic measurements on 6-8 suggest ligand non-innocent redox behavior in these complexes. PMID- 22669326 TI - Pulsed high-dose dexamethasone improves interleukin 10 secretion by CD5+ B cells in patients with primary immune thrombocytopenia. AB - BACKGROUND: B cells expressing CD5 are potentially capable of producing interleukin 10 (IL-10) which contributes to the regulatory function of B cells. This study was aimed at exploring the alteration of numbers of CD5(+) B cells and their ability of producing IL-10 in patients with immune thrombocytopenia (ITP), and the effects of pulsed high-dose dexamethasone (HD-DXM) therapy on CD5(+) B cells. METHODS: Peripheral blood mononuclear cells from 25 adult ITP patients were stained with PE-CD5/FITC-CD19 antibodies for flow cytometry analyses before and after HD-DXM therapy. The expression of IL-10 mRNA was measured by RT-PCR. After 24 h culture with or without dexamethasone in the presence of PMA, ionomycin and Brefeldin A, cells were permeabilized and stained with APC-IL-10 antibody to investigate intracellular IL-10 expression. Supernatant IL-10 concentration was detected by ELISA. RESULTS: The number of CD5(+) B cells was elevated in patients with ITP. Expression of IL-10 mRNA, percentage of IL-10(+) cells and intracellular IL-10 in CD5(+) B cells from untreated patients were significantly higher than that in controls. In contrast, ITP patients showed lower IL-10 concentration in supernatants than controls. After HD-DXM therapy, the number of CD5(+) B cells decreased to normal level, while intracellular IL-10 expression in CD5(+) B cells was further enhanced and IL-10 concentration in supernatants was also increased. Similar results were observed when dexamethasone was administrated in vitro. CONCLUSIONS: Increased number of CD5(+) B cells in which IL-10 is accumulated with decreased IL-10 concentration in supernatants suggests that the ability of CD5(+) B cells to secret IL-10 is impaired in ITP patients. Both the aberrant number and ability of IL-10 secretion of CD5(+) B cells could be corrected by HD-DXM. PMID- 22669328 TI - Strategies for sustaining a quality improvement collaborative and its patient safety gains. AB - OBJECTIVE: To identify strategies to facilitate the sustainability of a quality and safety improvement collaborative: the Safer Patients Initiative (SPI) and its successes. DESIGN: A qualitative interview study with a repeated sample at two time points. SETTING: Twenty organizations participating in the SPI programme in the UK. PARTICIPANTS: Twenty principal SPI programme coordinators took part in interviews towards the end of the supported phase of the programme, 12 of which were interviewed again a year later, along with another three replacement programme coordinators, totalling 35 interviewees across the two time points. MAIN OUTCOME MEASURES: Programme coordinators' perceptions of facilitating strategies to the sustainability of the collaborative and its gains. RESULTS: Qualitative analysis identified three overarching factors for the sustainability of SPI: (i) using programme improvement methodology and measurement of its outcomes; (ii) organizational strategies to ensure sustainability and (iii) alignment of goals with external requirements. Within these were eight themes identified by the coordinators as helping to sustain the efforts of the SPI programme and its successes. CONCLUSIONS: This study has presented what principle programme coordinators across 20 NHS organizations considered to be the key strategies to sustain their own improvement programme and its successes, during the supported phase of the programme and 1 year on. Recommendations are to consider these practical strategies in order to improve chances of maintaining changes and continuing a quality improvement programme beyond the formal cessation of the intervention. PMID- 22669329 TI - The contralateral subfrontal approach can simplify surgery and provide favorable visual outcome in tuberculum sellae meningiomas. AB - The ipsilateral approach for the tumor-dominant or amblyopic side in surgery of tuberculum sellae meningiomas (TSMs) frequently requires manipulation of the optic nerve and unroofing of the optic canal, which results in postoperative visual aggravation. We suggest a contralateral approach and discuss the benefits with respect to the postoperative visual outcome. Between 2005 and August 2011, 24 patients with TSMs underwent surgical resection via the contralateral approach. The contralateral approach accesses the tumor from the opposite side of the tumor-dominant or amblyopic side. Using this technique, the tumor was separated from the noncompromised optic nerve with only internal debulking. The tumor was dissected from the optic nerve without manipulation of the compromised optic nerve under the direct view of the inferomedial aspect of the optic nerve. The tumor that extended into the optic canal could be removed easily via dural unroofing of the medial wall of the optic canal. Seventeen patients (70.8 %) were improved, 6 (25 %) were unchanged, and 1 (4.2 %) worsened on visual acuity of the affected eye. Fifteen (62.5 %) were improved, 8 (33.3 %) were unchanged, and 1 patient (4.2 %) worsened on visual field defect of the affected eye. However, deterioration of visual acuity and visual field defect of the nonaffected eye was developed in one (4.2 %) and three patients (12.5 %), respectively. Surgical approach-related visual field defect was developed on two patients (8.3 %). The contralateral approach reduces manipulation of the involved optic nerve and directly visualizes the inferomedial aspect of the compromised optic nerve which could result in improvement of postoperative visual outcomes. PMID- 22669330 TI - The association of education with long-term weight change in the EPIC-PANACEA cohort. AB - BACKGROUND/OBJECTIVES: Cross-sectionally, educational attainment is strongly associated with the prevalence of obesity, but this association is less clear for weight change during adult life. The objective of this study is to examine the association between educational attainment and weight change during adult life in the European Prospective Investigation into Cancer and Nutrition (EPIC). SUBJECTS/METHODS: EPIC is a cohort study with 361,467 participants and up to 10 years of follow-up. Educational attainment was categorized according to the highest obtained school level (primary school or less, vocational secondary training, other secondary education and university). Multivariate mixed-effects linear regression models were used to study education in relation to weight at age 20 years (self-reported), to annual change in weight between age 20 years and measured weight at recruitment, and to annual change in weight during follow-up time. RESULTS: Higher educational attainment was associated with on average a lower body mass index (BMI) at age 20 years and a lower increase in weight up to recruitment (highest vs lowest educational attainment in men: -60 g per year (95% confidence interval (CI) -80; -40), women -110 g per year (95% CI -130; -80)). Although during follow-up after recruitment an increase in body weight was observed in all educational levels, gain was lowest in men and women with a university degree (high vs low education -120 g per year (95% CI -150; -90) and 70 g per year (95% CI -90; -60), respectively). CONCLUSIONS: Existing differences in BMI between higher and lower educated individuals at early adulthood became more pronounced during lifetime, which possibly impacts on obesity-related chronic disease risk in persons with lower educational attainment. PMID- 22669331 TI - Rapid onset of Wernicke's syndrome after gastric balloon positioning. PMID- 22669332 TI - Administration of omega-3 fatty acids and Raloxifene to women at high risk of breast cancer: interim feasibility and biomarkers analysis from a clinical trial. AB - BACKGROUND/OBJECTIVES: The antiestrogen, Raloxifene (Ral) is an effective breast cancer chemopreventive agent. Omega-3 fatty acids (n-3FA) may inhibit mammary carcinogenesis. On the basis of their mechanisms of action, we test the hypothesis that a combination of n-3FA and Ral may be superior in reducing select biomarkers of breast cancer risk in women. SUBJECTS/METHODS: Postmenopausal women at increased risk for breast cancer (breast density >= 25%) were randomized to: (1) no intervention; (2) Ral 60 mg; (3) Ral 30 mg; (4) n-3FA (Lovaza) 4 g and (5) Lovaza 4 g+Ral 30 mg for 2 years. Reduction in breast density is the primary end point of the study. We report preliminary data on feasibility, compliance and changes in secondary end points related to IGF-I signaling, estrogen metabolism, oxidative stress and inflammation in the first group of 46 women who completed 1 year of the study. RESULTS: All interventions were well tolerated with excellent compliance (96 +/- 1% overall) by pill count and also supported by the expected rise in both serum n-3FA and n-3FA/Omega-6 fatty acids (n-6FA) ratio in women randomized to groups 4 and 5 (P<0.05). Lovaza decreased serum triglycerides and increased high-density lipoprotein (HDL) cholesterol compared with control (P<0.05 for both). Ral reduced serum IGF-1 in a dose-dependent manner (P<0.05) while Lovaza did not. Lovaza had no effect on IGF-1 or IGFBP-3. None of the other biomarkers were affected by our treatment. CONCLUSION: The combination of Lovaza and Ral is a feasible strategy that may be recommended in future breast cancer chemoprevention trials. PMID- 22669333 TI - Short-term low carbohydrate/high-fat diet intake increases postprandial plasma glucose and glucagon-like peptide-1 levels during an oral glucose tolerance test in healthy men. AB - BACKGROUND/OBJECTIVES: Postprandial hyperglycemia increases the risks of development of type 2 diabetes and cardiovascular diseases. The purpose of this study was to determine whether a 3-day low-carbohydrate/high-fat diet (LC/HFD) alters postprandial plasma glucose and incretin levels during oral glucose tolerance test (OGTT) in healthy men. SUBJECTS/METHODS: Nine healthy young men (age (mean +/- s.e.), 27 +/- 1 years; body mass index, 22 +/- 1 kg/m(2)) consumed either a normal diet (ND: energy from ~22% fat) or a LC/HFD (energy from ~69% fat) for 3 days each. The total energy intake from each diet was similar. An OGTT was performed after each 3-day dietary intervention. Postprandial plasma glucose, insulin, free fatty acid and glucagon-like peptide-1 (GLP-1) levels were determined at rest and during the OGTT. RESULTS: Plasma glucose levels and incremental area under the curve during the OGTT were significantly higher in the LC/HFD trial than in the ND trial (P=0.024). In addition, increase in GLP-1 levels was significantly higher in the LC/HFD trial than in the ND trial (P=0.025). The first-phase insulin secretion indexes were significantly lower in the LC/HFD trial than in the ND trial (P<0.041). CONCLUSIONS: These results demonstrate that even short-term LC/HFD increased postprandial plasma glucose and GLP-1 levels in healthy young men. A decrease in first-phase insulin secretion may partially contribute to the short-term LC/HFD-induced increase in postprandial plasma glucose levels. PMID- 22669334 TI - A preclinical and clinical study of mycophenolate mofetil in pancreatic cancer. AB - A high throughput screening for anticancer activity of FDA approved drugs identified mycophenolic acid (MPA), an inhibitor of inositol monophosphate dehydrogenase (IMPDH) as an active agent with an antiangiogenesis mode of action. Exposure of pancreatic cancer cell lines to MPA resulted in growth inhibition and reduced the expression of VEGF that was reversed by supplementing the media with guanosine supporting and IMPDH-dependant mechanism. In preclinical in vivo study, MPA showed a moderate inhibition of tumor growth in a panel of 6 human derived pancreatic cancer xenografts but reduced the expression of VEGF. To investigate the effects of MPA in human pancreatic cancer, a total of 12 patients with resectable pancreatic cancer (PDA) received increasing doses of mycophenolate mofetil (MMF) in cohorts of 6 patients each from 5-15 days prior to surgical resection. Treatment was well tolerated with one episode of grade 1 muscle pain, one episode of grade 2 lymphopenia (2 gr/day dose) and one episode of grade 2 elevantion in LFT (all in the 2 gr./day dose). Patients recovered from surgery uneventfully with no increased post-operative complications. Assessment of CD31, VEGF, and TUNEL in resected specimens compared to a non treated control of 6 patients showed no significant variations in any of the study endpoints. In conclusion, this study shows the feasibility of translating a preclinical observation to the clinical setting and to explore a drug mechanism of action in patients. MPA, however, did not show any hints of antiangiogenesis of anticancer clinical activity questioning if this agent should be further developed in PDA. PMID- 22669335 TI - Additive effects of vorinostat and MLN8237 in pediatric leukemia, medulloblastoma, and neuroblastoma cell lines. AB - PURPOSE: Histone deacetylase (HDAC) inhibitors, such as vorinostat, decrease Aurora kinase activity by a variety of mechanisms. Vorinostat and MLN8237, a selective Aurora A kinase inhibitor, disrupt the spindle assembly and the mitotic checkpoint at different points, suggesting that the combination could have increased antitumor activity. The purpose of this study was to determine the cytotoxicity of vorinostat and MLN8237 in pediatric tumor cell lines. METHODS: Cell survival was measured after 72 h of drug treatment using a modified methyl tetrazolium assay. For drug combination experiments, cells were exposed to medium alone (controls), single drug alone, or to different concentrations of the combination of the two drugs, for a total of 36 concentration pairs per plate. The interaction of the drug combination was analyzed using the universal response surface approach. RESULTS: The cells express the target of MLN8237, Aurora A. For each cell line, the single agent IC(50) for MLN8237 and for vorinostat was in the clinically relevant range. Both drugs inhibited cell survival in a concentration dependent fashion. At concentrations of MLN8237 exceeding approximately 1 MUM, there was a paradoxical increase in viability signal in all three lines that may be explained by inhibition of Aurora B kinase. The combination of MLN8237 and vorinostat showed additive cytotoxicity in all three cell lines and nearly abrogated the paradoxical increase in survival noted at high single-agent MLN8237 concentrations. CONCLUSION: MLN8237 and vorinostat are active in vitro against cancer cell lines. These results provide important preclinical support for the development of future clinical studies of MLN8237and vorinostat. PMID- 22669336 TI - Biodegradation of oil spill by petroleum refineries using consortia of novel bacterial strains. AB - Feasibility study carried out at the site prior to the full scale study showed that the introduced bacterial consortium effectively adapted to the local environment of the soil at bioremediation site. The soil samples were collected from the contaminated fields after treatment with bacterial consortium at different time intervals and analyzed by gas chromatography after extraction with hexane and toluene. At time zero (just before initiation of bioremediation), the concentration of total petroleum hydrocarbons in the soil (25-cm horizon) of plot A, B, C and D was 30.90 %, 18.80 %, 25.90 % and 29.90 % respectively, after 360 days of treatment with microbial consortia was reduced to 0.97 %, 1.0 %, 1.0 %, and 1.1 % respectively. Whereas, only 5 % degradation was observed in the control plot after 365 days (microbial consortium not applied). PMID- 22669337 TI - Logic circuit upon angiogenic response controlled by enzyme-linked iron oxide microparticles--towards biocomputing in human cells. AB - In the present study, we designed a logic circuit upon angiogenic response controlled by a combination of enzyme-functionalized magnetic microparticles operating in human umbilical vein endothelial cells (HUVECs). The reported results represent the first example of a biocomputing system operating in controlling angiogenesis. PMID- 22669338 TI - Computed tomography coronary angiography accuracy in women and men at low to intermediate risk of coronary artery disease. AB - OBJECTIVES: To investigate the diagnostic accuracy of CT coronary angiography (CTCA) in women at low to intermediate pre-test probability of coronary artery disease (CAD) compared with men. METHODS: In this retrospective study we included symptomatic patients with low to intermediate risk who underwent both invasive coronary angiography and CTCA. Exclusion criteria were previous revascularisation or myocardial infarction. The pre-test probability of CAD was estimated using the Duke risk score. Thresholds of less than 30 % and 30-90 % were used for determining low and intermediate risk, respectively. The diagnostic accuracy of CTCA in detecting obstructive CAD (>=50 % lumen diameter narrowing) was calculated on patient level. P < 0.05 was considered significant. RESULTS: A total of 570 patients (46 % women [262/570]) were included and stratified as low (women 73 % [80/109]) and intermediate risk (women 39 % [182/461]). Sensitivity, specificity, PPV and NPV were not significantly different in and between women and men at low and intermediate risk. For women vs. men at low risk they were 97 % vs. 100 %, 79 % vs. 90 %, 80 % vs. 80 % and 97 % vs. 100 %, respectively. For intermediate risk they were 99 % vs. 99 %, 72 % vs. 83 %, 88 % vs. 93 % and 98 % vs. 99 %, respectively. CONCLUSION: CTCA has similar diagnostic accuracy in women and men at low and intermediate risk. KEY POINTS : * Coronary artery disease (CAD) is increasingly investigated by computed tomography angiography (CTCA). * CAD detection or exclusion by CTCA is not different between sexes. * CTCA diagnostic accuracy was similar between low and intermediate risk sex-specific groups. * CTCA rarely misses obstructive CAD in low-intermediate risk women and men. * CAD yield by invasive coronary angiography after positive CTCA is similar between sex-risk-specific groups. PMID- 22669339 TI - Passive/aggressive detoxification of continuous flow biotreatment systems using absorptive polymers: partitioning bioreactors treating transient phenol loadings. AB - Biotreatment of wastewaters containing toxic compounds can be jeopardized by surges in substrate concentration. Preventative measures include tight monitoring and control to either dilute high concentration transients, or to divert them to surge tanks for later release and treatment. Using phenol as a typical toxic substrate, we have imposed 4 h phenol surges of 3,000, 6,000 and 8,000 mg/l from a steady-state feed of 500 mg/l, demonstrating such reduced treatment efficiency. In contrast, with the addition to the bioreactor of a small amount (3-10 % w/v) of inert polymer beads (Hytrel 8206) possessing a high affinity for phenol (partition coefficient of 39), significant detoxification was achieved, resulting in a 100 % increase in treatment efficiency, and good performance at phenol surges of up to 16,000 mg/l. The addition (passive operation) of polymers to a biotreatment system eliminated the need for intervention during toxic transients while, at the same time, demonstrating that the polymers perform this function automatically and at all times (aggressive operation). PMID- 22669340 TI - Engineering efficient xylose metabolism into an acetic acid-tolerant Zymomonas mobilis strain by introducing adaptation-induced mutations. AB - The impact of the two adaptation-induced mutations in an improved xylose fermenting Zymomonas mobilis strain was investigated. The chromosomal mutation at the xylose reductase gene was critical to xylose metabolism by reducing xylitol formation. Together with the plasmid-borne mutation impacting xylose isomerase activity, these two mutations accounted for 80 % of the improvement achieved by adaptation. To generate a strain fermenting xylose in the presence of high acetic acid concentrations, we transferred the two mutations to an acetic acid-tolerant strain. The resulting strain fermented glucose + xylose (each at 5 % w/v) with 1 % (w/v) acetic acid at pH 5.8 to completion with an ethanol yield of 93.4 %, outperforming other reported strains. This work demonstrated the power of applying molecular understanding in strain improvement. PMID- 22669341 TI - [Ethic rounds in intensive care. Possible instrument for a clinical-ethical assessment in intensive care units]. AB - Ethical problems, such as medical end-of-life decisions or withdrawing life sustaining treatment are viewed as an essential task in intensive care units. This article presents the ethics rounds as an instrument for evaluation of ethical problems in intensive care medicine units. The benchmarks of ethical reflection during the ethics rounds are considerations of ethical theory of principle-oriented medical ethics. Besides organizational aspects and the institutional framework, the role of the ethicist is described. The essential evaluation steps, as a basis of the ethics rounds are presented. In contrast to the clinical ethics consultation, the ethicist in the ethics rounds model is integrated as a member of the ward round team. Therefore ethical problems may be identified and analyzed very early before the conflict escalates. This preventive strategy makes the ethics rounds a helpful instrument in intensive care units. PMID- 22669342 TI - Ureteroscopy-assisted retrograde nephrostomy (UARN) for an incomplete double ureter. PMID- 22669343 TI - Using a multi-component indicator toward reducing phytoplankton bloom occurrences in the Swan River estuary. AB - The Swan River estuary is an icon of the city of Perth, Western Australia, running through the city centre and dividing the northern from the southern part of the city. However, frequent phytoplankton blooms have been observed in the estuary as a result of eutrophication. The Index of Sustainable Functionality (ISF), a composite index able to indicate for sustainable health of the estuary, was applied, taking into account the hydrology and highly seasonal nature of the estuary to inform the management of the estuary, towards the aim of reducing bloom occurrences. The study period was from the beginning of intensive monitoring in 1995 to mid-2009. The results emphasize the importance of physical controls on the ecology of the estuary. No significant trend in the estuary's low functionality was found, indicating that despite extensive restoration efforts, the frequency of algal bloom occurrences has remained relatively stationary and other mitigating factors have maintained an annual average ISF value at around 70 % functionality. We identified that the low flow season consistently performs the worst, with (high) temperature found as the most dominant variable for phytoplankton growth and bloom. Thus in managing the estuary, vigilance is required during periods of high temperature and low flow. Focusing on the risk of phytoplankton bloom, a nutrient reduction program that is in place is a long term solution due to high concentrations in the estuary. Other management measures need to be considered and adopted to effectively reduce the occurrences of future phytoplankton blooms. PMID- 22669344 TI - Anaphylaxis on reperfusion during liver transplantation with coagulopathy. AB - We present a case in which anaphylaxis on hepatic reperfusion during liver transplantation presented only with hypotension and coagulopathy. There were no cutaneous manifestations or clinical features distinguishing anaphylaxis from postreperfusion syndrome. The recipient regularly consumed seafood, and the organ donor died of anaphylaxis to shellfish. The trigger for anaphylaxis was postulated to be passive transfer of immunoglobulin to the recipient. Anesthesiologists should be notified of donor factors to anticipate anaphylaxis. In this report, we discuss coagulopathy of anaphylaxis and contrast it with disseminated intravascular coagulation. PMID- 22669345 TI - Special article: retained guidewires after intraoperative placement of central venous catheters. AB - Guidewire retention is a rare complication of central venous catheter placement, and has been related to operator fatigue, inexperience, and inattention, and inadequate supervision of trainees. The true incidence of guidewire loss after intraoperative placement of central venous catheters is unknown. We report 4 cases of guidewire loss after central venous access procedures performed by anesthesia providers in the operating room. Worsening of patients' clinical condition during catheter placement and complex procedures necessitating more than one guidewire insertion are recurring scenarios in cases involving guidewire loss. Over 6 years at our institution, intraoperative wire loss occurred at a rate of 1:3291 procedures (95% confidence interval of 1/10,000 to 8/10,000). PMID- 22669346 TI - A novel computerized fading memory algorithm for glycemic control in postoperative surgical patients. AB - BACKGROUND: Hyperglycemia is commonly encountered in critically ill patients and is associated with increased mortality and morbidity. To better control blood glucose levels, we previously developed a new computerized fading memory (FM) algorithm. In this study we evaluated the safety and efficacy of this algorithm in surgical intensive care unit (SICU) patients and compared its performance against the existing insulin-infusion algorithm (named VA algorithm) used in our institution. METHODS: A computer program was developed to run the FM and VA algorithms. Forty eight patients, who were scheduled to have elective surgery, were randomly assigned to receive insulin infusion on the basis of either the FM or VA algorithm. On SICU admission, an insulin infusion was either continued from the operating room or initiated when the glucose level exceeded the target level of 140 mg/dL. Hourly blood glucose measurements were performed and entered into the computer program, which then prescribed the next insulin dose. The randomly assigned algorithm was applied for the first 8 hours of SICU stay, after which the VA algorithm was used. The number of episodes of hypoglycemia (glucose <60 mg/dL) and excessive hyperglycemia (>300 mg/dL) were noted. Additionally, the time required to bring the glucose level within target range (140 +/- 20 mg/dL), the number of glucose measurements within the target range, glycemic variability, and insulin usage were analyzed and compared between the 2 algorithms. RESULTS: Patient demographics and starting glucose levels were similar between the groups. With the existing VA algorithm, 1 episode of severe hypoglycemia was observed. Three patients did not reach the target range within 8 hours. With the FM algorithm no hypoglycemia occurred, and all patients achieved the target range within 8 hours. Glycemic variability measured by the SD of mean glucose levels was 28% (95% confidence interval, 14% to 39%) lower for the FM algorithm (P < 0.001). The FM algorithm used 1.1 U/h less insulin than did the VA algorithm (P = 0.043). CONCLUSION: The novel computerized FM algorithm for glycemic control, which emulates physiologic biphasic insulin secretion, managed glucose better than the existing algorithm without any episodes of hypoglycemia. The FM algorithm had less glycemic variability and used less insulin when compared to the conventional clinical algorithm. PMID- 22669347 TI - Postoperative analgesic and behavioral effects of intranasal fentanyl, intravenous morphine, and intramuscular morphine in pediatric patients undergoing bilateral myringotomy and placement of ventilating tubes. AB - BACKGROUND: Bilateral myringotomy and placement of ventilating tubes (BMT) is one of the most common pediatric surgical procedures in the United States. Many children who undergo BMT develop behavioral changes in the postanesthesia care unit (PACU) and require rescue pain medication. The incidence of these changes is lower in children receiving intraoperative opioids by the nasal, IM, or IV route compared with placebo. However, there are no data to indicate which route of administration is better. Our study was designed to compare the immediate postoperative analgesic and behavioral effects of 3 frequently used intraoperative techniques of postoperative pain control for patients undergoing BMT under general anesthesia. METHODS: One hundred seventy-one ASA physical status I and II children scheduled for BMT were randomized into 1 of 3 groups: group 1-nasal fentanyl 2 MUg/kg with IV and IM saline placebo; group 2-IV morphine 0.1 mg/kg with nasal and IM placebo; or group 3-IM morphine 0.1 mg/kg with nasal and IV placebo. All subjects received a standardized general anesthetic with sevoflurane, N(2)O, and O(2) and similar postoperative care. The primary end point of the study was the pain scores measured by the Faces, Legs, Activity, Cry, and Consolability (FLACC) scale in the PACU. RESULTS: There were no significant differences in peak FLACC pain among the 3 groups (mean [95% CI] 2.0 [1.2-2.8] for intranasal fentanyl, 2.7 [1.7-3.6] for IV morphine, and 2.9 [2.1-3.7] for IM morphine, respectively). There were no differences in the scores on the Pediatric Anesthesia Emergence Delirium (PAED) scale, incidence of postoperative emergence delirium (PAED score >= 12), emesis, perioperative hypoxemia, or need for airway intervention, and postoperative rescue analgesia. There were also no differences in the duration of PACU stay or parental satisfaction among the groups. CONCLUSION: In this double-blind, double-dummy study, there was no difference in the efficacy of intranasal fentanyl, IM and IV morphine in controlling postoperative pain and emergence delirium in children undergoing BMT placement. The IM route is the simplest and avoids the potential for delays to establish vascular access for IV therapy and the risks of laryngospasm if intranasal drugs pass through the posterior nasopharynx and irritate the vocal cords. PMID- 22669348 TI - Synthesis of anti-HIV lithospermic acid by two diverse strategies. AB - An efficient and convergent route for the synthesis of the natural product (+) lithospermic acid, which possesses anti-HIV activity, was accomplished. The (+/-) trans-dihydrobenzo[b]furan core therein was prepared by two different strategies. The first strategy involved the use of a palladium-catalyzed annulation to generate an appropriately substituted benzo[b]furan ester followed by a stereoselective reduction of a carbon-carbon double bond with Mg-HgCl(2)-MeOH. The second strategy relied on an aldol condensation between a suitably substituted methyl arylacetate and 3,4-dimethoxybenzaldehyde, followed by cyclization. Finally, a total synthesis of (+)-lithospermic acid was completed via coupling of a trans-dihydrobenzo[b]furan cinnamic acid with an enantiomerically pure methyl lactate. PMID- 22669349 TI - Recent advances in tomato functional genomics: utilization of VIGS. AB - Tomato unquestionably occupies a significant position in world vegetable production owing to its world-wide consumption. The tomato genome sequencing efforts being recently concluded, it becomes more imperative to recognize important functional genes from this treasure of generated information for improving tomato yield. While much progress has been made in conventional tomato breeding, post-transcriptional gene silencing (PTGS) offers an alternative approach for advancement of tomato functional genomics. In particular, virus induced gene silencing (VIGS) is increasingly being used as rapid, reliable, and lucrative screening strategy to elucidate gene function. In this review, we focus on the recent advancement made through exploiting the potential of this technique for manipulating different agronomically important traits in tomato by discussing several case studies. PMID- 22669350 TI - Seasonal variation in myopia progression and axial elongation: an evaluation of Japanese children participating in a myopia control trial. AB - PURPOSE: To investigate the seasonal variations in myopia progression and axial elongation in Japanese children. METHODS: Ninety-two children who were enrolled in a myopia-control trial and wearing single vision or progressive addition lenses were included in the analyses (mean +/- SD age 11.4 +/- 1.7 years, mean spherical equivalent refractive error -4.40 +/- 1.38 D). Refractive error and axial length were measured every 6 months for 1.5 years by non-cycloplegic autorefraction and partial coherence interferometer, respectively. Myopia progression and axial elongation for each 6-month interval were calculated by subtracting the measure at the end of the interval from that at the beginning. Seasons were classified as summer, winter or others, based on mid-day of the 6 month period between visits. RESULTS: Myopia progression was not significantly influenced by the season. After adjusting study groups (type of spectacles), years and age at the baseline, the mean (+/-SE) myopia progression was 0.35 +/- 0.04 D for summer, 0.28 +/- 0.06 D for winter and 0.38 +/- 0.04 D for the others. In contrast, axial elongation was significantly influenced by the season, and the mean axial elongation was 0.137 +/- 0.010 mm for summer, 0.170 +/- 0.013 mm for winter and 0.163 +/- 0.008 mm for the others. The seasonal variation in axial elongation, however, was smaller than that previously reported overseas. CONCLUSIONS: In Japanese children myopia progression did not slow in summer. Although axial elongation slightly decreased in summer, myopia progression seems to be fairly stable throughout the year. PMID- 22669351 TI - Comparison of efficacy of four prostaglandin analogues by bilateral treatment in healthy subjects. AB - PURPOSE: To compare the drug efficacy of four prostaglandin analogues (PGAs) by bilateral treatment in normal subjects. METHODS: Three consecutive studies comparing latanoprost to three other PGAs (travoprost, tafluprost and bimatoprost) were performed in 24 healthy subjects. Each study was separated by a washout period of over 6 weeks. In each study, two drugs were randomly assigned to one eye of each subject. Study subjects instilled the assigned medication at 9:00 p.m. every day for 2 weeks. The same masked investigator measured intraocular pressure (IOP) at 9:00 a.m., 1:00 p.m. and 5:00 p.m. at baseline and repeated measurements on days 7 and 14. The differences in IOP reduction were compared between the drugs. RESULTS: Mean diurnal IOP reduction with latanoprost on days 7 and 14 was similar to that with travoprost and tafluprost, but was significantly lower than that with bimatoprost. The association of the mean diurnal IOP reduction between latanoprost and bimatoprost on day 14 (r (2) = 0.25) was weak, in remarkable contrast to the strong association between latanoprost and travoprost (r (2) = 0.81) and between latanoprost and tafluprost (0.82). CONCLUSIONS: The short-term bilateral treatment revealed a different IOP lowering efficacy of bimatoprost compared to other PGAs in healthy subjects. PMID- 22669352 TI - Validation of a measurement to predict upper airway collapsibility during sedation for colonoscopy. AB - Techniques to quantify the effects of sedation on upper airway collapsibility have been used as research tools in the laboratory and operating room. However, they have not been used previously in the usual clinical practice environment of colonoscopy sedation. The propensity for upper airway collapsibility, quantified as the critical pharyngeal pressure (P(crit)), was hypothesized to correlate with the need for clinical intervention to maintain ventilation. Twenty patients scheduled for colonoscopy with sedation were prospectively recruited to undergo measurement of upper airway collapsibility using negative airway pressure (NAP) provocation with a minimum pressure of -18 cmH(2)O. The P(crit) was the negative pressure that collapses the airway, either directly or by extrapolation from the pressure-flow relationship. An exponential transformation was applied to the P(crit) data for statistical analysis. A clinical intervention score (CIS) was used to quantify required interventions by the sedation nurse. The measurement of the P(crit) during sedation was significantly larger (less negative) than both the baseline ("awake") (P = 0.0029) and late recovery (P = 0.01) values. The CIS was not predicted by the transformed baseline or sedated P(crit) with or without including demographics associated with sleep apnea syndrome. Although the NAP technique showed the expected changes with sedation in this clinical situation, we did not find that it predicted the need for clinical intervention during endoscopy. Our study was not large enough to test for subpopulations in which the test might be predictive; further studies of these particular groups are needed to determine the clinical utility of the NAP measurement. PMID- 22669353 TI - Longitudinal change in dysarthria associated with Friedreich ataxia: a potential clinical endpoint. AB - CNS functions that show change across short periods of time are particularly useful clinical endpoints for Friedreich ataxia. This study determined whether there is measurable acoustical change in the dysarthria associated with Friedreich ataxia across yearly intervals. A total of 29 participants diagnosed with Friedreich ataxia were recorded across 4 years at yearly intervals. A repeated measures ANOVA was used to determine which acoustic measures differed across time, and pairwise t tests were used to assess the consistency of the change across the time intervals. The relationship between the identified measures with perceptual severity was assessed with stepwise regression. Significant longitudinal change was observed with four measures that relate to the utterance duration and spectral changes in utterances. The spectral measures consistently detected change across time intervals of two or more years. The four measures combined moderately predicted perceptual severity. Together, the results implicate longitudinal change in speaking rate and utterance duration. Changes in speech associated with Friedreich ataxia can be measured across intervals of 2 years and therefore show rich potential for monitoring disease progression and therapy outcomes. PMID- 22669354 TI - CSF abnormalities can be predicted by VEP and MRI pathology in the examination of optic neuritis. AB - Optic neuritis (ON) is linked to multiple sclerosis (MS). The presence of white matter lesions on cerebral magnetic resonance imaging (MRI) predicts the risk of MS after ON with considerable accuracy. Oligoclonal bands (OCB) are present in 95 % of MS patients, and a lumbar puncture can also be valuable in the evaluation of patients with ON. We analyzed CSF findings in patients referred with ON in the context of MRI and visual evoked potential (VEP) pathology. We assessed the possible contributory role of a lumbar puncture and weigh this against disadvantages of the procedure. Between February 2003 and November 2011, 505 patients were referred by ophthalmologists to the Clinic of Optic Neuritis, Glostrup Hospital, University of Copenhagen. None had MS prior to referral. A total of 437 were included in the study, and all underwent MRI, a lumbar puncture and VEP. Patients with other organic causes of their symptoms and patients with >3 months between onset and tests were excluded. All files were reviewed retrospectively. CSF leukocytes and the IgG index were elevated in 33 and 41 %, respectively, and OCBs were detected in 61 % of patients. CSF abnormalities correlated strongly with VEP and MRI (p < 0.0001). Patients with normal VEP and MRI had a 96 % probability of a normal lumbar puncture. The contributory role of a lumbar puncture in the evaluation of ON seems negligible when patients have a normal VEP and MRI. We suggest that all patients should be evaluated with VEP and MRI before deciding on a lumbar puncture. PMID- 22669355 TI - Support of the concept of interhemispheric rivalry by two consecutive strokes occurring in both hemispheres: a case study. PMID- 22669356 TI - [Please don't hurt me!: a plea against invasive procedures in children and adolescents with complex regional pain syndrome (CRPS)]. AB - BACKGROUND: Complex regional pain syndrome (CRPS; formerly known as Morbus Sudeck/reflex dystrophy) is diagnosed in children and adolescents, but the clinical presentation is often atypical. Unfortunately, potentially harmful, invasive treatments are used in pediatric patients. PATIENTS AND METHODS: A retrospective chart study of pediatric chronic pain patients with CRPS was performed. RESULTS: Over the course of 6 years, 37 (35 girls) children and adolescents took part in a multidisciplinary chronic pain inpatient program. At admission, patients took on average 4.4 (range 1-10) different medications and 29 different pharmaceuticals were used overall. Prior to admission, invasive pain treatments were performed without success in 16 of the children (43%). At least 13 children received two or more invasive treatments. Although sympathetic blocks were most prevalent, operations and regional anesthesia were also used. CONCLUSION: Despite a lack of evidence for invasive procedures, these continue to be used in children and adolescents with CRPS, who later respond positively to conventional treatment. The English full-text version of this article is available at SpringerLink (under "Supplemental"). PMID- 22669357 TI - Late retirement is not associated with increased mortality, results based on all Swedish retirements 1991-2007. PMID- 22669358 TI - The relation between socioeconomic status and short-term mortality after acute myocardial infarction persists in the elderly: results from a nationwide study. AB - We assessed whether the previously observed relationship between socioeconomic status (SES) and short-term mortality (pre-hospital mortality and 28-day case fatality) after a first acute myocardial infarction (AMI) in persons <75 years, are also observed in the elderly (i.e. >=75 years), and whether these relationships vary by sex. A nationwide register based cohort study was conducted. Between January 1st 1998 and December 31st 2007, 76,351 first AMI patients were identified, of whom 60,498 (79.2 %) were hospitalized. Logistic regression analyses were performed to measure SES differences in pre-hospital mortality after a first AMI and 28-day case-fatality after a first AMI hospitalization. All analyses were stratified by sex and age group (<55, 55-64, 65-74, 75-84, >=85), and adjusted for age, ethnic origin, marital status, and degree of urbanization. There was an inverse relation between SES and pre hospital mortality in both sexes. There was also an inverse relation between SES and 28-day case-fatality after hospitalization, but only in men. Compared to elderly men with the highest SES, elderly men with the lowest SES had a higher pre-hospital mortality in both 75-84 year-olds (OR = 1.26; 95 % CI 1.09-1.47) and >=85 year-olds (OR = 1.26; 1.00-1.58), and a higher 28-day case-fatality in both 75-84 year-olds (OR = 1.26; 1.06-1.50) and >=85 year-olds (OR = 1.36; 0.99-1.85). Compared to elderly women with the highest SES, elderly women with the lowest SES had a higher pre-hospital mortality in >=85 year-olds (OR = 1.20; 0.99-1.46). To conclude, in men there are SES inequalities in both pre-hospital mortality and case-fatality after a first AMI, in women these SES inequalities are only shown in pre-hospital mortality. The inequalities persist in the elderly (>=75 years of age). Clinicians and policymakers need to be more vigilant on the population with a low SES background, including the elderly. PMID- 22669359 TI - Catalyst-controlled reversal of chemoselectivity in acylation of 2-aminopentane 1,5-diol derivatives. AB - Highly chemo- and regioselective acylation of 2-aminopentane-1,5-diol derivatives has been achieved by organocatalysis. An acyl group can be chemoselectively introduced onto the sterically hindered secondary hydroxy group in the presence of the primary one by virtue of the molecular recognition event of the catalyst. PMID- 22669360 TI - Evaluation of sexual function in women at two stages of multiple sclerosis. AB - PURPOSE: In the present study, we aimed to evaluate the sexual function in patients with multiple sclerosis (MS) who were examined in two subgroups and compare the results to the control group with a validated questionnaire. METHODS: A total of 23 consecutive female MS patients divided into groups with relapsing remitting MS (RRMS) and secondary progressive MS (SPMS) and 45 healthy control subjects were included into the study. The inclusion criteria were as follows: Definite MS, age between 18 and 60 years and an Expanded Disability Status Scale (EDSS) score of <8. The neurologic impairment, the disability and the independence of the patient, and cognitive performances were measured, and also the effect of MS is evaluated by EDSS. RESULTS: No statistically significant difference was found between two groups. FSFI scores in both groups were significantly lower than the control group. Domain scores for desire, arousal, orgasm, pain, lubrication and satisfaction measured between RRMS and SPMS patients showed no significant difference. Comparing each domain score for arousal, orgasm and satisfaction revealed significantly lower scores in RRMS and SPMS patients compared to control group. CONCLUSIONS: In this study, we detected statistically significant decrease in FSFI scores in two groups of MS compared to healthy controls. We could not define a difference in sexual function in different stages of MS in women and a statistically significant negative correlation between EDSS and FSFI scores in the two subgroups of MS. PMID- 22669361 TI - Phase I trial of docetaxel, oxaliplatin, and capecitabine (DOC) in untreated gastric cancer patients. AB - BACKGROUND: A combination of docetaxel (D), oxaliplatin (O), and capecitabine (C) (DOC) was studied in this dose-escalation phase Ib trial in patients with untreated advanced gastric cancer. METHODS: Dose-limiting toxicity (DLT) included any grade 4 hematological or any grade 3 non-hematological toxicity, besides alopecia and nausea or vomiting. Cohorts of three patients, expanded to six if one DLT occurred, were studied. Two DLTs out of three patients, or >=3 out of six patients defined the toxic level. The preceding level, maximum tolerated dose (MTD), was further expanded to nine patients. The primary objective was to establish the MTD of the DOC regimen. RESULTS: Twenty-one patients entered four dose levels. Levels I, II, and IIb were considered safe and included 3, 6, and 6 patients, respectively. Level III defined our toxic level with three analyzed patients. Therefore, level IIB was expanded to 9 patients. No other DLTs were recorded. CONCLUSIONS: Fractionation of doses and the use of less toxic and more convenient derivatives are the rationales for this new combination. The MTD (mg/m(2)) was: D, 30 and O, 70, both on days 1 and 8, i.v.; C 1000 per day, days 2-15, p.o.; all given every 3 weeks. A cooperative phase II study has been opened. PMID- 22669362 TI - Complications in ankle arthroscopy. AB - PURPOSE: To determine the complication rate for ankle arthroscopy. METHODS: A review of a consecutive series of patients undergoing ankle arthroscopy in our hospital between 1987 and 2006 was undertaken. Anterior ankle arthroscopy was performed by means of a 2-portal dorsiflexion method with intermittent soft tissue distraction. Posterior ankle arthroscopy was performed by means of a two portal hindfoot approach. Complications were registered in a prospective national registration system. Apart from this complication registry, patient records, outpatient charts and operative reports were reviewed. Patients with a complication were asked to visit our hospital for clinical examination and assessment of permanent damage and persisting complaints. RESULTS: An overall complication rate of 3.5% in 1,305 procedures was found. Neurological complications (1.9%) were related to portal placement. Age was a significant risk factor for the occurrence of complications. Most complications were transient and resolved within 6 months. Complications did not lead to functional limitations. Residual complaints did not influence daily activities. CONCLUSIONS: Our complication rate is less than half of what has been reported in literature (3.5 vs 10.3%). The use of the dorsiflexion method for anterior ankle arthroscopy can prevent a significant number of complications. Posterior ankle arthroscopy by means of a two-portal hindfoot approach is a safe procedure with a complication rate that compares favourably to that of anterior ankle arthroscopy. LEVEL OF EVIDENCE: Retrospective prognostic study, Level II. PMID- 22669364 TI - Maternal phenylketonuria: low phenylalaninemia might increase the risk of intra uterine growth retardation. AB - BACKGROUND: Malformations and mental retardation in the offspring of women with Phenylketonuria (PKU) can be prevented by maintaining maternal blood Phenylalanine (PHE) within a target range (120-300 MUmol/L) through a PHE restricted diet. In a former French study, a high and unexpected proportion of intra uterine growth retardation (IUGR) has been reported. Guidelines have been proposed to all French centres caring for maternal PKU since 2002. OBJECTIVE: To confirm IUGR and investigate its causes. The other goals were to assess the follow-up of these pregnancies based on the new guidelines and the pertinence of these recommendations. DESIGN: Clinical, biological and ultrasound data of all pregnancies in PKU women in France, from 2002 to 2007 were retrospectively analyzed. RESULTS: Data from 115 pregnancies in 86 women with PKU were collected. Ninety percent of women had been informed of the risk of maternal PKU in the absence of a strict diet during pregnancy, 88 % of women had started a diet before conception, and 45 % of infants were born small for gestational age (birth length and/or weight <=-2 SD). PHE intakes were lower in the group with IUGR from the fifth to the eighth month of pregnancy and duration of time spent at <120 MUmol/L during pregnancy was associated with a higher risk of IUGR. CONCLUSION: Hyperphenylalaninemia (HPA) is not the only risk factor for IUGR; PHE lower than 120 MUmol/L could also be associated with the IUGR occurrence. Even if the monitoring of these pregnancies has been improved since the initiation of guidelines, we would like to stress on the importance of the dietary aspect of the disease. PMID- 22669363 TI - Enzyme replacement therapy for mucopolysaccharidosis VI: long-term cardiac effects of galsulfase (Naglazyme(r)) therapy. AB - Characteristic cardiac valve abnormalities and left ventricular hypertrophy are present in untreated patients with mucopolysaccharidosis type VI (MPS VI). Cardiac ultrasound was performed to investigate these findings in subjects during long-term enzyme replacement therapy (ERT) with recombinant human arylsulfatase B (rhASB, rhN-acetylgalactosamine 4-sulfatase, galsulfase, Naglazyme(r)). Studies were conducted in 54 subjects before ERT was begun and at specific intervals for up to 96 weeks of weekly infusions of rhASB at 1 mg/kg during phase 1/2, phase 2, and phase 3 trials of rhASB. At baseline, mitral and aortic valve obstruction was present and was significantly greater in those >=12 years of age. Mild mitral and trace aortic regurgitation were present, the former being significantly greater in those <12 years. Left ventricular hypertrophy, with averaged z-scores ranging from 1.6-1.9 SD greater than normal, was present for ages both <12 and >=12 years. After 96 weeks of ERT, ventricular septal hypertrophy regressed in those <12 years. For those >=12 years, septal hypertrophy was unchanged, and aortic regurgitation increased statistically but not physiologically. Obstructive gradients across mitral and aortic valves remained unchanged. The results suggest that long-term ERT is effective in reducing intraventricular septal hypertrophy and preventing progression of cardiac valve abnormalities when administered to those <12 years of age. PMID- 22669365 TI - Klaas Westerterp; editorial board member, EJCN. Interview. PMID- 22669366 TI - In both Norwegian and English. PMID- 22669367 TI - [Is the answer even more pills?]. PMID- 22669368 TI - [Kind physicians and work-shy patients again?]. PMID- 22669369 TI - [Confusion regarding evidence-based advice]. PMID- 22669370 TI - [Unreasonable thoughts about evidence]. PMID- 22669373 TI - [Overdiagnosis in mammography screening]. PMID- 22669374 TI - [Failing statistics on breast cancer]. PMID- 22669376 TI - [Proton pump inhibitors prevent drug-induced bleeding ulcers]. PMID- 22669378 TI - [Permanent jobs for specialists--necessary and forward-looking]. PMID- 22669379 TI - [Epilepsy--controversial proposal on new classification]. PMID- 22669380 TI - [Irresponsibly on male circumcision]. PMID- 22669381 TI - Evidence-based practice for patients with severe venous thrombosis. PMID- 22669382 TI - [Patterns in the prescription of antihypertensive drugs in Norway, 1975-2010]. AB - BACKGROUND: A complete overview of drugs used for hypertension is not available from official data sources. The aim of this study was to investigate the use of blood pressure medication over the years to identify trends in consumption patterns. MATERIAL AND METHOD: Data were collected from the Norwegian drug wholesaler statistics for the years 1975-2010 and from the Norwegian prescription database 2004-2010. Defined daily doses (DDD) per 1000 inhabitants per day, number of users and prevalence by gender and age were analysed. RESULTS: In the period 1975 to 2010 the use of antihypertensives increased from 55 to 248 DDD/1000 inhabitants/day (Norwegian drug wholesaler statistics). Data from the Norwegian prescription database show that in 2010 there were a total of 754 909 users of antihypertensives, of whom 638 830 had received the diagnosis hypertension. Thiazides and angiotensin II antagonists had the greatest increase in number of users from 2004 to 2010. In all ages up to 73 years, a higher proportion of men were prescribed drugs for hypertension in 2010, whereas in the over-73 s these drugs were most widely used by women. INTERPRETATION: The use of antihypertensives is steadily increasing. Angiotensin II antagonists and thiazides are the most commonly used drugs. The authorities'' decision in 2004 that thiazides should be regarded as first-line therapy for hypertension probably contributed to increased use of thiazides. PMID- 22669383 TI - [Sickness absence associated with major life events]. AB - BACKGROUND: Sickness absence in the Norwegian workplace doubled in the period 1993-2003. However, the extent to which the driving factors were medical or non medical remains unclear, as does the extent to which the cause may be found in the composition of the workforce. MATERIAL AND METHODS: A differences-in differences regression model was used to estimate the added sickness absence associated with major life events such as separation, death of spouse and pregnancy in the period 1993-2005. The data were obtained from administrative registers covering the entire Norwegian population, and include all absence periods of 16 days' duration or more reported by a doctor's medical certificate. The primary outcome measures were incidence (the proportion of absentees in a given time window) and absence (the proportion of sick days in a given time window). The level of absence among employees exposed to the specified life events was compared to control groups matched for gender, age, education and income. RESULTS: In 1993, people in each of the three groups exposed to major life events had more frequent and longer periods of absence than people in the control groups. This added sickness absence increased between 1993 and 2005. The changes in added sickness absence were at times significant, particularly for pregnant women. While sickness absence among pregnant women in 1993 was 15.4 percentage points higher than in the control group, the difference had increased to 24.8 percentage points in 2005. INTERPRETATION: We find it improbable for the increase in added sickness absence to be caused by changes in the medical impact of life events or alterations in the workforce composition. We believe the increase is caused by changing attitudes among the working population and in the medical profession towards sickness absence on grounds that are not strictly medical, combined with improved social acceptance and diagnosis of mental health issues, and/or a medicalisation of natural health variations (pregnancy) and emotional distress (grief). PMID- 22669384 TI - Organ donation and Norwegian doctors' need for training. AB - BACKGROUND: The skill of the person who asks about organ donation and the timing of the conversation may have an impact on the likelihood of obtaining consent from a patient's relatives. The purpose of the study was to investigate the experience that intensive care doctors and neurosurgeons have of treating organ donors and communicating with their relatives, as well as the doctors' own learning needs. MATERIAL AND METHOD: In 2008, we sent a questionnaire to all doctors at all intensive-care units at all donor hospitals in Norway, and to all neurosurgeons/neurosurgical trainees. RESULTS: Altogether 435 doctors (55 per cent) responded to the questionnaire. Of these, 63 per cent were specialists in intensive care medicine. More than half had little experience of organ donation or how to relate to the patients' relatives. Many of them reported a need to learn more about the medical issues associated with organ donation and about communication in this situation. INTERPRETATION: Many doctors fail to adhere to recommended practice in their encounters with relatives. Training programmes should focus especially on communication with relatives. PMID- 22669385 TI - [Combination treatment of depression]. AB - Severe depression is a common diagnosis and a number of studies have demonstrated the superiority of antidepressants to placebos. More than half of the patients remain depressed despite initial treatment. If reasons like incorrect diagnosis and non-optimal choice of drug or doses are excluded, combination therapy may be considered. Augmentation of antidepressants with lithium or the thyroid hormone T3 has documented effectiveness, mainly with tricyclic antidepressants, but is not frequently used. Less documentation exists for a combination of two antidepressant drugs, but their use is relatively common. PMID- 22669386 TI - [A young man with swallowing difficulties]. PMID- 22669387 TI - [An exemplary course of treatment--because it happened in the Oslo city center?]. PMID- 22669388 TI - [Middle-aged female presenting with headache, blurred vision and skin rash]. AB - BACKGROUND: Autoimmune hyperlipidemia (AIH) is a rare cause of secondary hyperlipidemia. A few cases of AIH have been reported in multiple myeloma. MATERIAL AND METHODS: A female in her fifties was referred to the outpatient clinic presenting with headache, blurred vision and skin rash. Physical examination with subsequent laboratory and histological examinations revealed severe hyperlipidemia secondary to secretory multiple myeloma with monoclonal IgG kappa protein and erythrocytosis secondary to a erythropoietin secreting adenoma in the liver. RESULTS AND INTERPRETATION: Treatment for multiple myeloma (induction treatment and autologous hematological stem cell transplantation) gained partial remission and was associated with normalization of serum lipids. There was no need for further medical treatment of the hyperlipidemia. Three years after the initial treatment, serum concentrations of triglycerides and total cholesterol increased in parallel with monoclonal IgG kappa protein. Total cholesterol and triglycerides decreased and remained within the reference ranges after retreatment with a second autologous stem cell transplantation. Surgical removal of the hepatic adenoma caused normalisation of the erythropoietin concentration and resolution of the erythrocytosis. The present case reports two rare complications (AIH and erythrocytosis) to multiple myeloma and hepatic adenoma, with regression of complaints and normalisation of laboratory tests after adequate treatment of underlying diseases. PMID- 22669389 TI - [Pharmaceuticals as pollution]. AB - The pharmaceuticals we humans use to treat illness and disease typically enter the aquatic environment via the sewer network and wastewater treatment works. Understanding the risks posed to the aquatic environment by these chemicals requires an understanding of the concentrations that exist in the environment and whether they are sufficiently high to have adverse effects on aquatic organisms. The main source of pharmaceuticals to wastewater treatment works is pharmaceuticals used by the general population. Only a small contribution is believed to come from hospitals. The predicted environmental concentrations of pharmaceuticals suggest that certain pharmaceuticals may pose a risk to the environment, but measurement of the actual concentrations present in effluents and recipient waters suggest that sophisticated wastewater treatment is effective for significantly reducing effluent concentrations, and that environmental concentrations of pharmaceuticals, in the Oslo Fjord, for example, are generally low. Humans also excrete the metabolites of the pharmaceuticals that they have used and these too may be released into the environment, sometimes in greater concentrations than the parent drug. The occurrence of most pharmaceuticals and their metabolites in the environment poses little acute environmental risk. However, the effects of long-term chronic exposure to these compounds are still poorly understood and the long-terms risks to the environment are still not clear. What is clear is that certain pharmaceuticals pose a greater environmental risk than others, and that where possible this knowledge should be used to inform users of more environmentally friendly alternatives. PMID- 22669390 TI - High-flying anatomy (with a dash of clinical ornithology). PMID- 22669393 TI - Assessment of accuracy and efficiency of atlas-based autosegmentation for prostate radiotherapy in a variety of clinical conditions. AB - BACKGROUND AND PURPOSE: The goal of the current study was to evaluate the commercially available atlas-based autosegmentation software for clinical use in prostate radiotherapy. The accuracy was benchmarked against interobserver variability. MATERIAL AND METHODS: A total of 20 planning computed tomographs (CTs) and 10 cone-beam CTs (CBCTs) were selected for prostate, rectum, and bladder delineation. The images varied regarding to individual (age, body mass index) and setup parameters (contrast agent, rectal balloon, implanted markers). Automatically created contours with ABAS((r)) and iPlan((r)) were compared to an expert's delineation by calculating the Dice similarity coefficient (DSC) and conformity index. RESULTS: Demo-atlases of both systems showed different results for bladder (DSC(ABAS) 0.86 +/- 0.17, DSC(iPlan) 0.51 +/- 0.30) and prostate (DSC(ABAS) 0.71 +/- 0.14, DSC(iPlan) 0.57 +/- 0.19). Rectum delineation (DSC(ABAS) 0.78 +/- 0.11, DSC(iPlan) 0.84 +/- 0.08) demonstrated differences between the systems but better correlation of the automatically drawn volumes. ABAS((r)) was closest to the interobserver benchmark. Autosegmentation with iPlan((r)), ABAS((r)) and manual segmentation took 0.5, 4 and 15-20 min, respectively. Automatic contouring on CBCT showed high dependence on image quality (DSC bladder 0.54, rectum 0.42, prostate 0.34). CONCLUSION: For clinical routine, efforts are still necessary to either redesign algorithms implemented in autosegmentation or to optimize image quality for CBCT to guarantee required accuracy and time savings for adaptive radiotherapy. PMID- 22669394 TI - [MRI mammography screening in women with lobular carcinoma in situ]. PMID- 22669395 TI - [Efficacy of adjuvant zoledronic acid in breast cancer therapy remains unclear]. PMID- 22669396 TI - [Organ-sparing chemoradiotherapy: a viable alternative to initial cystectomy for patients with muscle-invasive bladder cancer]. PMID- 22669397 TI - Evolution of the crystal and magnetic structure of the R2MnRuO7 (R = Tb, Dy, Ho, Er, Tm, Yb, Lu, and Y) family of pyrochlore oxides. AB - The members of the family of pyrochlore oxides with the formula R(2)MnRuO(7) (R = Tb, Dy, Ho, Er, Tm, Yb, Lu and Y) have been synthesized and characterized. Polycrystalline samples were prepared by a soft chemistry procedure involving citrates of the different metal ions, followed by thermal treatments in air or O(2) pressure. The crystallographic and magnetic structures have been analysed from X-ray diffraction (XRD) and neutron powder diffraction (NPD) data, in complement with magnetic measurements; the evolution along the series of the crystallographic parameters (unit-cell parameters, bond distances and angles) is discussed. In R(2)MnRuO(7) pyrochlores, Mn and Ru ions statistically occupy the 16c sites in a cubic unit cell with space group Fd 3m, which defines an intrinsic frustrated three-dimensional system. In all the cases, the low-temperature NPD data unveils an antiferromagnetic coupling of two subsets of Mn(4+)/Ru(4+) spins, indicating that the magnetic frustration is partially relieved by the random distribution of Mn and Ru over the 16c sites. At lower temperatures there is a polarization of the R(3+) magnetic moments, which also participate in the magnetic structure, when a magnetic rare earth is present. PMID- 22669398 TI - Microsatellite instability is associated with a better prognosis for gastric cancer patients after curative surgery. AB - BACKGROUND: Microsatellite instability (MSI) is one of the leading mechanisms for the carcinogenesis of gastric cancer. Its prognostic value is controversial. METHODS: Between May 1988 and Oct 2003, a total of 214 gastric cancer patients undergoing curative surgery were enrolled, and their MSI statuses were classified as MSI-H (high) or MSI-L/S (low/stable). The clinicopathologic characteristics of MSI-H and MSI-L/S gastric cancers were compared. RESULTS: The MSI-H tumors accounted for 11.7 % (n = 25) of the 214 total gastric cancers. Although not statistically significant, the MSI-H gastric cancers were more frequently located in the lower third of the stomach (64 % vs. 49.2 %) and were more often the intestinal type (72 % vs. 61.4 %) compared to the MSI-L/S gastric cancers. The MSI-H gastric cancers had a significantly better 5-year overall survival (OS) rate (68 % vs. 47.6 %, p = 0.030) and a trend of a better 3-year disease-free survival rate (71.8 % vs. 55.2 %, p = 0.076) compared to the MSI-L/S gastric cancers. A multivariate analysis revealed that pathologic TNM stage and MSI status were the independent prognostic factors for OS after curative surgery. CONCLUSIONS: Compared to MSI-L/S tumors, MSI-H tumors are associated with a better OS rate for gastric cancer patients after R0 resection. PMID- 22669399 TI - Guided treatment improves outcome of patients with enterocutaneous fistulas. AB - BACKGROUND: The present study was designed to evaluate the effects of guided treatment of patients with an enterocutaneous fistula and to evaluate the effect of prolonged period of convalescence on outcome. METHODS: All consecutive patients with an enterocutaneous fistula treated between 2006 and 2010 were included in this study. Patient information was gathered prospectively. Treatment of patients focused on sepsis control, optimization of nutritional status, wound care, establishing the anatomy of the fistula, timing of surgery, and surgical principles. Outcome included spontaneous and surgical closure, mortality, and postoperative recurrence. The relationship between period of convalescence and recurrence rate was determined by combining the present prospective cohort with a historical cohort from our group. RESULTS: Between 2006 and 2010, 79 patients underwent focused treatment for enterocutaneous fistula. Cox regression analysis showed that period of convalescence related significantly with recurrence of the fistula (hazard ratio 0.99; 95 % confidence interval 0.98-0.999; p = 0.04). Spontaneous closure occurred in 23 (29 %) patients after a median period of convalescence of 39 (range 7-163) days. Forty-nine patients underwent operative repair after median period of 101 (range 7-374) days and achieved closure in 47 (96 %). Overall, eight patients (10 %) died. CONCLUSIONS: Prolonging period of convalescence for patients with enterocutaneous fistulas improves spontaneous closure and reduces recurrence rate. PMID- 22669400 TI - Wound healing after open appendectomies in adult patients: a prospective, randomised trial comparing two methods of wound closure. AB - BACKGROUND: The skin is closed in open appendectomy traditionally with few interrupted nonabsorbable sutures. The use of this old method is based on a suggestion that this technique decreases wound infections. In pediatric surgery, skin closure with running intradermal absorbable sutures has been found to be as safe as nonabsorbable sutures, even in complicated cases. Our purpose was to compare the safety of classic interrupted nonabsorbable skin closure to continuous intradermal absorbable sutures in appendectomy wounds in adult patients. METHODS: A total of 206 adult patients with clinically suspected appendicitis were allocated to the study and prospectively randomized into two groups of wound closure: the interrupted nonabsorbable (NA) suture and the intradermal continuous absorbable (A) suture group. Primary wound healing was controlled on the first postoperative day, at 1 week clinically and after 2 weeks by means of a telephone interview. Follow-up data were obtained from 185 patients (90 in group NA and 95 in group A). RESULTS: Continuous absorbable intradermal suturing was as safe as nonabsorbable sutures in regard to wound infections. CONCLUSION: Continuous, absorbable sutures can be used safely even in complicated appendicectomies without increasing the risk of wound infection. Considering the benefits of absorbable suturing, we recommend this method in all open appendectomies. PMID- 22669401 TI - Treatment of common bile duct stones in Sweden 1989-2006: an observational nationwide study of a paradigm shift. PMID- 22669402 TI - Rationale and design of an International Multicenter Registry of patients with repaired tetralogy of Fallot to define risk factors for late adverse outcomes: the INDICATOR cohort. AB - Although early survival after tetralogy of Fallot (TOF) repair in the modern era is excellent, studies on late outcomes have shown increasing rates of mortality and morbidity. Despite multiple publications on factors associated with late complications, risk factors for major outcomes (death and sustained ventricular tachycardia [VT]) remain poorly defined. Consequently, the International Multicenter TOF Registry (INDICATOR) was established. This article describes the development, structure, and goals of this registry and characterizes the initial cohort derived from four large congenital heart centers in the United States, Canada, and Europe. A data coordinating center with a core cardiac magnetic resonance (CMR) laboratory and statistical core was established. Subjects with repaired TOF who had CMR imaging performed between 1997 and 2010 and >= 1 year follow-up were included. Clinical end points were death and sustained VT. Demographic, electrophysiologic, exercise, and outcome data were collected. A total of 873 subjects fulfilled inclusion criteria (median age at repair 2.9 years and at CMR imaging 22.8 years). Of these, 9 % had QRS duration >180 ms on electrocardiogram (ECG). On CMR imaging, 38 % had severe right-ventricular (RV) dilatation (>= 160 mL/m(2)), and 6 % had severe RV dysfunction (ejection fraction < 35 %). Of the 551 subjects with exercise testing available, 28 % had severely decreased exercise capacity with <50 % predicted peak oxygen consumption. The INDICATOR cohort allows robust statistical analysis to evaluate major clinical outcomes in patients with repaired TOF. Continued follow-up and further expansion of the registry may provide new insights into innovative therapeutic strategies to improve late outcomes. PMID- 22669403 TI - Involvement of hippocampal CAMKII/CREB signaling in the spatial memory retention induced by creatine. AB - Although Creatine (Cr) and Phosphocreatine (PCr) systems play a key role in cellular energy and energy transport in neuronal cells, its implications for learning and memory are still controversial. Thus, we decided to investigate the involvement of cAMP-dependent protein kinase A (PKA), Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and cAMP responsive element binding protein (CREB) in the spatial consolidation after an intrahippocampal injection of Cr. Statistical analysis revealed that Cr (2.5 nmol/hippocampus) (post-training) decreased the latency for escape and the mean number of errors on Barnes maze test. Post training co-administration of the PKA inhibitor (H-89 25 rhomol/hippocampus) did not alter the facilitatory effect of Cr in this memory test. On the other hand, Cr-induced spatial retention was reverted by co-administration of the CaMKII inhibitor (STO-609 5 nmol/hippocampus). Neurochemical analysis revealed that intrahippocampal injection of Cr, when analyzed after 30 min rather than after 3 h, increased the levels of pCREB and pCaMKII but not pPKA levels. Statistical analysis also revealed that the post-training co-administration of STO-609 but not H-89 reversed the increase of pCREB levels induced by Cr. The results presented in this report suggest that intracellular CaMKII/CREB pathway plays a key role in the Cr-induced spatial retention. Thus, it is plausible to propose that Cr plays a putative role as a neuromodulator in the brain, and that at least some of its effects may be mediated by intracellular CaMKII/CREB pathway. PMID- 22669404 TI - Growth of regional acute stroke systems of care in the United States in the first decade of the 21st century. AB - BACKGROUND AND PURPOSE: States and counties in the US began implementing regional systems of acute stroke care in the first decade of the 21st century, whereby emergency medical services systems preferentially route acute stroke patients directly to primary stroke centers. The pace, geographic range, and population reach of regional stroke system implementation has not been previously delineated. METHODS: We performed a review of legislative archives, internet and media reports, consultation with American Heart Association/American Stroke Association and Centers for Disease Control staff, and phone interviews with state public health and emergency medical service officials from each of the 50 states. RESULTS: The first counties to adopt regional regulations supporting routing of acute stroke patients to primary stroke centers were in Alabama and Texas in 2000; the first states were Florida and Massachusetts in 2004. By 2010, 16 states had state-level legislation or regulations to enable emergency medical service routing to primary stroke centers, as did counties in 3 additional states. The US population covered by routing protocols increased substantially in the latter half of the decade, from 1.5% in 2000 to 53% of the US population by the end of 2010. CONCLUSIONS: The first decade of the 21st century witnessed a remarkable structural transformation in acute stroke care: by the end of 2010, over half of all Americans were living in states/counties with emergency medical service routing protocols supporting the direct transport of acute stroke patients to primary stroke centers. Additional efforts are needed to extend regional stroke systems of care to the rest of the US. PMID- 22669405 TI - Hull down on the horizon: A Randomized trial of Unruptured Brain Arteriovenous malformations (ARUBA) trial. PMID- 22669406 TI - A perfect storm: how a randomized trial of unruptured brain arteriovenous malformations' (ARUBA's) trial design challenges notions of external validity. PMID- 22669407 TI - Drip-and-ship thrombolytic treatment paradigm among acute ischemic stroke patients in the United States. AB - BACKGROUND AND PURPOSE: To provide a national assessment of thrombolytic administration using drip-and-ship treatment paradigm. METHODS: Patients treated with the drip-and-ship paradigm among all acute ischemic stroke patients treated with thrombolytic treatment were identified within the Nationwide Inpatient Sample. Thrombolytic utilization, patterns of referral, comparative in-hospital outcomes, and hospitalization charges related to drip-and-ship paradigm were determined. All the in-hospital outcomes were analyzed after adjusting for potential confounders using multivariate analysis. RESULTS: Of the 22 243 ischemic stroke patients who received thrombolytic treatment, 4474 patients (17%) were treated using drip-and-ship paradigm. Of these 4474 patients, 81% were referred to urban teaching hospitals for additional care, and 7% of them received follow-up endovascular treatment. States with a higher proportion of patients treated using the drip-and-ship paradigm had higher rates of overall thrombolytic utilization (5.4% versus 3.3%; P<0.001). The rate of home discharge/self-care was significantly higher in patients treated with drip-and-ship paradigm compared with those who received thrombolytics through primary emergency department arrival in the multivariate analysis (OR, 1.198; 95% CI, 1.019-1.409; P=0.0286). CONCLUSIONS: One of every 6 thrombolytic-treated patients in United States is treated using drip-and-ship paradigm. States with the highest proportion of drip and-ship cases were also the states with the highest thrombolytic utilization. PMID- 22669408 TI - Bd on the beach: high prevalence of Batrachochytrium dendrobatidis in the lowland forests of Gorgona Island (Colombia, South America). AB - The amphibian chytrid fungus, Batrachochytrium dendrobatidis, Bd, has been implicated in the decimation and extinction of many amphibian populations worldwide, especially at mid and high elevations. Recent studies have demonstrated the presence of the pathogen in the lowlands from Australia and Central America. We extend here its elevational range by demonstrating its presence at the sea level, in the lowland forests of Gorgona Island, off the Pacific coast of Colombia. We conducted two field surveys, separated by four years, and diagnosed Bd by performing polymerase chain reactions on swab samples from the skin of five amphibian species. All species, including the Critically Endangered Atelopus elegans, tested positive for the pathogen, with prevalences between 3.9 % in A. elegans (in 2010) and 52 % in Pristimantis achatinus. Clinical signs of chytridiomycosis were not detected in any species. To our knowledge, this is the first report of B. dendrobatidis in tropical lowlands at sea level, where temperatures may exceed optimal growth temperatures of this pathogen. This finding highlights the need to understand the mechanisms allowing the interaction between frogs and pathogen in lowland ecosystems. PMID- 22669409 TI - Intraocular PAS-positive macrophages simulating Whipple's disease. PMID- 22669410 TI - Microsatellite instability testing in Korean patients with colorectal cancer. AB - Microsatellite instability (MSI) testing is useful for identifying patients with hereditary nonpolyposis colorectal cancer and detecting sporadic colorectal cancer that develops through replication error pathways. A pentaplex panel is recommended by the National Cancer Institute for MSI testing, but simplified mononucleotide panels and immunohistochemistry of mismatch repair proteins are widely employed for convenience. This study was to evaluate the MSI status of colorectal cancer in Korean patients. This study included 1,435 patients with colorectal adenocarcinoma subjected to surgical resection. The pentaplex Bethesda panel was used for MSI testing. Seventy nine (5.5 %) carcinomas were classified as MSI-high (MSI-H) and 95 (6.6 %) as MSI-low (MSI-L). BAT-26 and BAT-25 were unstable in 73 and 75 of 79 MSI-H carcinomas, respectively. With the panel comprising these 2 mononucleotide markers, 72 carcinomas were diagnosed as MSI-H, compared to the Bethesda panel data (72/79, 91.1 %). In contrast, BAT-26 or BAT 25 were unstable in only 7 (7.4 %) of the 95 MSI-L tumors. In the panel with 2 dinucleotide markers, D17250 linked to p53 and D2S123 to hMSH2, detection rates were 89.9 % (71/79) for MSI-H and 80.0 % (76/95) for MSI-L carcinomas, compared to the Bethesda panel. Moreover, we compared the frequency of MSI tumor in our patients with those reported previously from Western countries. In conclusion, the frequency of MSI-H appears lower in colorectal cancer patients in Korea. A simplified panel for MSI testing with BAT-26 and BAT-25 seems not effective for the accurate evaluation of MSI status, particularly in MSI-L colorectal carcinomas, in our patients. PMID- 22669411 TI - Quality of life and coping of women treated for breast cancer and their caregiver. What are the interactions? AB - This longitudinal study analyzed the interactions between the quality of life and the coping strategies of 100 patients treated for breast cancer and their caregivers. Data were collected after diagnosis, at the end of treatment, and 6 months after treatment with the Quality of Life Questionnaire-C30 (QLQ-C30), Duke Health Profile and Ways of Coping Checklist for both patients and caregivers. The theoretical model was tested using a typology of patients and mixed model analyses. The quality of life of patients changed over time and no cluster effect was found. The influence of the sociodemographic characteristics, coping strategies (patients and caregivers) and the quality of life of caregivers on patient's quality of life were different according to the quality of life dimensions considered. To understand the adaptation of patients to their disease, it is therefore essential to look at whether the caregiver is capable of playing a supporting role. PMID- 22669412 TI - Ligand-manipulated selective transformations of Au-Ni bimetallic heteronanostructures in an organic medium. AB - Here we demonstrated that Au can be more reactive than Ni in Au/Ni heteronanostructures and be etched out first by oxidization with HAuCl(4). Ligands were proven to determine the conversion pathways and structures of final products. These abnormal ligand-manipulated redox reactions may provide more possibilities for the chemical transformation of existing nanostructures into more complex ones. PMID- 22669413 TI - An urgent need for a change in policy revealed by a study on prenatal testing for Duchenne muscular dystrophy. AB - Prenatal diagnosis for Duchenne muscular dystrophy (DMD) was introduced in the Netherlands in 1984. We have investigated the impact of 26 years (1984-2009) of prenatal testing. Of the 635 prenatal diagnoses, 51% were males; nearly half (46%) of these were affected or had an increased risk of DMD. As a result 145 male fetuses were aborted and 174 unaffected boys were born. The vast majority (78%) of females, now 16 years or older, who were identified prenatally have not been tested for carrier status. Their average risk of being a carrier is 28%. We compared the incidences of DMD in the periods 1961-1974 and 1993-2002. The incidence of DMD did not decline but the percentage of first affected boys increased from 62 to 88%. We conclude that a high proportion of families with de novo mutations in the DMD gene cannot make use of prenatal diagnosis, partly because the older affected boys are not diagnosed before the age of five. Current policy, widely accepted in the genetic community, dictates that female fetuses are not tested for carrier status. These females remain untested as adults and risk having affected offspring as well as progressive cardiac disease. We see an urgent need for a change in policy to improve the chances of prevention of DMD. The first step would be to introduce neonatal screening of males. The next is to test females for carrier status if requested, prenatally if fetal DNA is available or postnatally even before adulthood. PMID- 22669414 TI - Publics and biobanks: Pan-European diversity and the challenge of responsible innovation. AB - This article examines public perceptions of biobanks in Europe using a multi method approach combining quantitative and qualitative data. It is shown that public support for biobanks in Europe is variable and dependent on a range of interconnected factors: people's engagement with biobanks; concerns about privacy and data security, and trust in the socio-political system, key actors and institutions involved in biobanks. We argue that the biobank community needs to acknowledge the impact of these factors if they are to successfully develop and integrate biobanks at a pan-European level. PMID- 22669415 TI - Partial deletion of GLRB and GRIA2 in a patient with intellectual disability. AB - We report about the partial de novo loss of GLRB and GRIA2 in an individual with intellectual disability (ID). No additional mutations were found in either gene. GLRB itself does not seem to be a good candidate as it causes autosomal recessive hyperekplexia and no symptoms were found in the patient. Mutations of GRIA2 have not been described as cause of ID to date. Nonetheless, it is a very attractive candidate because it encodes a subunit of a glutamate receptor, which is highly expressed in postsynaptic structures and has an important role in signal transduction across synapses. Although we were able to isolate a fragment of a fusion transcript of both genes from the patient's blood, we were not able to isolate a transcript with an open reading frame throughout the entire length. The reading frame could be restored by differential splicing, which might take place in brain tissue but not in blood. We assume that either haploinsufficiency of GRIA2 or a GLRB/GRIA2 fusion gene leading to a protein with dominant-negative properties is causing the phenotype of the patient. PMID- 22669416 TI - Expanded spectrum of Pelizaeus-Merzbacher-like disease: literature revision and description of a novel GJC2 mutation in an unusually severe form. AB - Homozygous or compound heterozygous mutations in the GJC2 gene, encoding the gap junction protein connexin47 (Cx47), cause the autosomal recessive hypomyelinating Pelizaeus-Merzbacher-like disease (PMLD1, MIM# 608804). Although clinical and neuroradiological findings resemble those of the classic Pelizaeus-Merzbacher disease, PMLD patients usually show a greater level of cognitive and motor functions. Unpredictably a homozygous missense GJC2 mutation (p.Glu260Lys) was found in a patient presenting with a very severe clinical picture characterised by congenital nystagmus and severe neurological impairment. Also magnetic resonance imaging was unusually severe, showing an abnormal supra- and infratentorial white matter involvement extending to the spinal cord. The novel p.Glu260Lys (c.778G>A) mutation, occurring in a highly conserved motif (SRPTEK) of the Cx47 extracellular loop-2 domain, was predicted, by modelling analysis, to break a 'salt bridge network', crucial for a proper connexin-connexin interaction to form a connexon, thus hampering the correct formation of the connexon pore. The same structural analysis, extended to the previously reported missense mutations, predicted that most changes were expected to have less severe impact on protein functions, correlating with the mild PMLD1 form of the patients. Our study expands the spectrum of PMLD1 and provides evidence that the extremely severe clinical and neuroradiological PMLD1 form of our patient likely correlates with the predicted impairment of gap junction channel assembly resulting from the detrimental effect of the new p.Glu260Lys mutant allele on Cx47 protein. PMID- 22669417 TI - REGENT: a risk assessment and classification algorithm for genetic and environmental factors. AB - The identification of environmental and genetic factors that contribute to disease risk requires appropriate statistical methods and software that can integrate different sources of risk, provide statistical assessment of combined risk factors, and facilitate interpretation of this risk. We have developed an R package, REGENT, to calculate risks conferred by genetic factors and multilevel environmental factors. This is performed at a population level, with the option to also analyse individual-level data. REGENT incorporates variability in risk factors to calculate confidence intervals for risk estimates and to classify the population into different categories of risk based on significant differences from the baseline average member of the population. REGENT is an R package available from CRAN: http://cran.r-project.org/web/packages/REGENT. It will be of value to genetic researchers exploring the utility of the variants detected for their disorder, and to clinical researchers interested in genetic risk studies. PMID- 22669418 TI - Intravitreal delivery of AAV-NDI1 provides functional benefit in a murine model of Leber hereditary optic neuropathy. AB - Leber hereditary optic neuropathy (LHON) is a mitochondrially inherited form of visual dysfunction caused by mutations in several genes encoding subunits of the mitochondrial respiratory NADH-ubiquinone oxidoreductase complex (complex I). Development of gene therapies for LHON has been impeded by genetic heterogeneity and the need to deliver therapies to the mitochondria of retinal ganglion cells (RGCs), the cells primarily affected in LHON. The therapy under development entails intraocular injection of a nuclear yeast gene NADH-quinone oxidoreductase (NDI1) that encodes a single subunit complex I equivalent and as such is mutation independent. NDI1 is imported into mitochondria due to an endogenous mitochondrial localisation signal. Intravitreal injection represents a clinically relevant route of delivery to RGCs not previously used for NDI1. In this study, recombinant adenoassociated virus (AAV) serotype 2 expressing NDI1 (AAV-NDI1) was shown to protect RGCs in a rotenone-induced murine model of LHON. AAV-NDI1 significantly reduced RGC death by 1.5-fold and optic nerve atrophy by 1.4-fold. This led to a significant preservation of retinal function as assessed by manganese enhanced magnetic resonance imaging and optokinetic responses. Intraocular injection of AAV-NDI1 overcomes many barriers previously associated with developing therapies for LHON and holds great therapeutic promise for a mitochondrial disorder for which there are no effective therapies. PMID- 22669419 TI - Vaginal laxity: a poorly understood quality of life problem; a survey of physician members of the International Urogynecological Association (IUGA). AB - INTRODUCTION AND HYPOTHESIS: Our goal was to assess how physician members of the International Urogynecological Association (IUGA) perceive and manage vaginal laxity. METHODS: An Internet-based survey was circulated targeting physician members of IUGA that consisted of 27 questions and was designed to query attitudes and practices with respect to vaginal laxity. RESULTS: Five hundred and sixty-three of the 2,235 surveys were completed (25% response rate). Most respondents (65% male and 35 % female) listed urogynecology as their specialty. The geographical distribution was Europe (39%), North America (23%), Asia (15%), South America (14%), Australia (6%), and Africa (3%). Eighty-three percent described laxity as underreported by their patients. The majority considered laxity a bothersome condition to patients that impacts relationship happiness and sexual function. The introitus was listed most often as being responsible for these symptoms. Whereas only 54% offered surgical treatment, surgery was cited as more effective than Kegel exercises or physical therapy. North Americans were more likely to prefer and perform surgical treatment for this problem. CONCLUSION: Vaginal laxity is common and may impact sexual function and quality of life. Expanding our knowledge regarding pathophysiology and treatment would be of benefit to these patients. PMID- 22669420 TI - Case report: transitional cell carcinoma in situ within a urethral diverticulum. AB - A 56-year-old female smoker presented after long diagnostic delay with high-grade transitional cell carcinoma in situ within a urethral diverticulum. This is the third report of this type in the literature. Preoperative investigations, including urine cytology and magnetic resonance imaging (MRI), were not helpful. PMID- 22669421 TI - Preoperative clinical, demographic, and urodynamic measures associated with failure to demonstrate urodynamic stress incontinence in women enrolled in two randomized clinical trials of surgery for stress urinary incontinence. AB - INTRODUCTION AND HYPOTHESIS: The unexpected absence of urodynamic stress incontinence (USI) in women planning surgery for stress urinary incontinence (SUI) is a challenge to surgeons. We examined the prevalence and clinical and demographic factors associated at baseline (preoperatively) with the unexpected absence of USI among study participants of two multicenter randomized clinical trials of surgery for treating SUI. METHODS: Women with SUI symptoms and positive stress tests on physical examination enrolled in two separate clinical trials-one comparing the autologous fascial sling with the Burch colposuspension [Stress Incontinence Surgical Treatment Efficacy Trial (SISTEr), and the other comparing the retropubic mid-urethral sling with the transobturator midurethral sling [Trial of Mid-Urethral Slings (TOMUS)]-were evaluated for USI preoperatively. The association of clinical, demographic, and urodynamic parameters was examined in women without USI in univariate and multivariate analyses. RESULTS: Overall, 144 of 1,233 women (11.7 %) enrolled in the two studies showed no USI. These women had a significantly lower mean volume at maximum cystometric capacity than those with USI (347.5 vs. 395.8 in SISTEr, p = 0.012), (315.2 vs. 358.2 in TOMUS, p = 0.003) and a lower mean number of daily accidents reported on a 3-day diary (2.2 vs 2.7 in SISTEr, p = 0.030) (1.7 vs 2.7 in TOMUS, p < 0.001). Additionally, those without demonstrable USI were more likely to have Pelvic Organ Prolapse Quantification (POP-Q) stage III/IV (31.7 % vs 14.4 % in SISTEr, p = 0.002), (15.5 % vs 6.9 % in TOMUS, p = 0.025). SUI severity as recorded on the Urogenital Distress Inventory (UDI) correlated strongly with the presence of USI in both studies. CONCLUSIONS: We observed that about one of eight women planning surgery for SUI does not show USI. Stage 3/4 POP was strongly associated with the unexpected absence of USI. A diminished urodynamic bladder capacity among women who did not display USI may reflect an inability to reach the limits of capacity during urodynamics, at which these women normally leak. PMID- 22669422 TI - Lighted stents facilitate robotic-assisted laparoscopic ureterovaginal fistula repair. AB - Three cases of ureterovaginal fistula (UVF) repair were reviewed in order to improve the minimally invasive surgical technique. We successfully repaired UVF robotically using five ports by placing a lighted ureteral stent preoperatively to assist with ureter identification and dissection. Placement of a lacrimal duct probe allowed fistula tract identification and obliteration. Preoperative surgical team planning is useful to avoid errors and delays. A multispecialty and an experienced robotic surgical team were paramount for the success of our robotic repair. PMID- 22669423 TI - Population-based trends in ambulatory surgery for urinary incontinence. AB - INTRODUCTION AND HYPOTHESIS: Surgical procedures for stress urinary incontinence (SUI) have become progressively less invasive and easier to perform with the development of new technologies such as the midurethral sling. For these reasons, it seems logical to conclude that midurethral slings would supplant other surgical treatments for incontinence. The purpose of this study was to assess the impact of this technology on trends in ambulatory surgery for incontinence over the past decade. METHODS: We searched Current Procedure Terminology codes and the State Ambulatory Surgery Database from 2001 through 2009 to identify all ambulatory procedures for incontinence. Next, we calculated age-adjusted rates separately for each procedure. We then fit a multilevel model to characterize patient and regional factors associated with the preferential use of midurethral slings over alternative treatments. RESULTS: Midurethral slings and submucosal injections comprised >90 % of all ambulatory procedures for SUI during the time period examined. Age-adjusted rates of midurethral slings increased dramatically, from 2.36 to 9.45/10,000 population (p < 0.001), whereas rates of submucosal injections remained relatively stable, from 1.75 to 1.41/10,000 population (p = 0.226). Not surprisingly, older ([odds ratio (OR) 0.61; 95 % confidence interval (CI) 0.56-0.66] and more infirm patients (OR 0.60; CI 0.44-0.83) were more likely to receive submucosal injection therapy than to receive midurethral slings. CONCLUSIONS: Rates of midurethral slings have increased significantly by fourfold. Rates of submucosal injections, however, have remained fairly stable during this time period, suggesting that sling dissemination has led to an increase in rates of incontinence procedures as opposed to replacing old technologies in the ambulatory setting. PMID- 22669424 TI - Pelvic floor disorders clinical trials: participant recruitment and retention. AB - INTRODUCTION AND HYPOTHESIS: We used a focus-group methodology to gather information about women's knowledge and attitudes regarding research participation. METHODS: Two in-person focus groups at seven clinical sites were conducted in women with pelvic floor disorder (PFD): one of women with clinical trial study experience and the other without such experience. One Web-based focus group combining both groups was also conducted. RESULTS: One hundred and five women (average age 58.6 years) participated. Participants in both groups believed that their physicians were the best source of information about clinical trials yet felt that other sources of trial information were important. Financial compensation was not a primary motivating factor for PFD trial enrollment but was, however, cited as an important consideration. Internet collection of data was feasible and provided information comparable with in-person focus groups. CONCLUSIONS: This study identified central themes guiding successful recruitment to and retention in PFD-related trials and provided insight regarding strategies that may guide future trials. PMID- 22669425 TI - Responsiveness of the Pelvic Floor Distress Inventory and Pelvic Floor Impact Questionnaire in women undergoing treatment for pelvic floor disorders. AB - INTRODUCTION AND HYPOTHESIS: This study evaluated the responsiveness and minimal important differences (MID) of the Chinese Pelvic Floor Distress Inventory (PFDI) and Pelvic Floor Impact Questionnaire (PFIQ) in women undergoing urodynamic stress incontinence (USI) and/or pelvic organ prolapse (POP) treatment. METHODS: One hundred and fifty-six women were assessed using the PFDI and PFIQ before and after they received continence surgery and or pelvic floor repair (PFR) surgery, or vaginal pessary. Symptom severity was recorded using a visual analog scale (VAS) before and after treatment as was rating of their satisfaction with the treatment they received. Responsiveness of the PFDI and PFIQ were evaluated by effect sizes, standardized response mean, paired samples t test or Wilcoxon Signed Rank Test. MID in the PFDI and PFIQ for different treatments were determined by satisfaction rating, change in VAS scoring, and distribution-based methods. RESULTS: There were significant improvements in the respective subscales of PFDI and PFIQ, demonstrating moderate to great responsiveness after different treatments. The estimation of MID for the Urinary Distress Inventory (UDI) was 30 to -14 and the Urinary Impact Questionnaire (UIQ) was -28 to -14 for women who underwent continence surgery. The MID for the Pelvic Organ Prolapse Distress Inventory (POPDI) was -44 to -21, the Pelvic Organ Prolapse Impact Questionnaire (POPIQ) -40 to -27, the UDI -22 to -16, the UIQ -37 to -31, the Colo-Rectal-Anal Distress Inventory (CRADI) -37 to -14, and the Colo-Rectal-Anal Impact Questionnaire (CRAIQ) -34 to -6 for women who underwent PFR surgery; and estimation of MID for the POPDI was -16, the POPIQ -29, the UDI -28, the UIQ -17, the CRADI -25, and the CRAIQ -31 for women who received a vaginal pessary. The MID of the respective subscales were supported by the distribution-based methods. CONCLUSIONS: The Chinese PFDI and PFIQ instruments are responsive to change in women undergoing continence surgery, PFR surgery or vaginal pessary for USI or POP. PMID- 22669426 TI - Estrogen inhibits vaginal tropoelastin and TGF-beta1 production. AB - INTRODUCTION AND HYPOTHESIS: The aim of this study was to quantify the effects of estrogen on vaginal smooth muscle cell (SMC) tropoelastin and transforming growth factor (TGF)-beta1 production. METHODS: Primary SMC were incubated with estradiol, and cell proliferation was assessed by 3-[4,5-dimethylthiazol-2-yl] 2,5-diphenyl tetrazolium bromide (MTT) assay at 48 h. Supernatants were collected and tropoelastin and TGF-beta1 levels measured. RESULTS: SMC proliferation was significantly increased by estradiol [relative cell number, mean +/- standard error (SE), estradiol 0.1 MUM 116 +/- 19 % of control (P = NS), 1 MUM 127 +/- 13 % of control (P < 0.05), 10 MUM 153 +/- 26 % of control, (P < 0.05)]. Tropoelastin production was significantly decreased by estrogen [mean +/- SE, estradiol 0.1 MUM 78 +/- 2 % of control (P < 0.05), 1 MUM 76 +/- 4 % of control (P < 0.05), 10 MUM 67 +/- 3 % of control, (P < 0.05)]. In addition, TGF-beta1 production was significantly decreased [mean +/- SE, estradiol 0.1 MUM 96 +/- 4 % of control (P = NS), 1 MUM 84 +/- 6 % of control (P < 0.05), 10 MUM 70 +/- 6 % of control, (P < 0.05)]. CONCLUSION: Estrogen increases vaginal SMC proliferation and inhibits tropoelastin and TGF-beta1 production. PMID- 22669427 TI - Perioperative experience of pelvic organ prolapse repair with the Prolift and Elevate vaginal mesh procedures. AB - INTRODUCTION AND HYPOTHESIS: We compared the operative and immediate postoperative experience of the trocar-based Prolift and non-trocar-based Elevate techniques used to repair vaginal prolapse. METHODS: A retrospective review of Prolift and Elevate repairs was performed. Baseline characteristics and operative and postoperative variables evaluated included compartment(s) repaired, adjacent organ injury, operative time (OT), change in hemoglobin (DeltaH), pain score, narcotic use, length of stay (LOS), and short-term complications. Categorical variables were assessed as counts and percent frequency. Data were compared using chi-squared analysis and paired t test. RESULTS: Prolift (n = 143) and Elevate (n = 77) patients were similar in age (p = 0.19). Concurrent hysterectomy was done in 22 (15.4 %) and 24 (31.2 %), respectively, and concurrent midurethral sling placed in 100 (70 %) and 50 (65 %), respectively. LOS (median, 25th,75th) after anterior/apical compartment repairs was shorter with Elevate, whether with (1.0; 1.0,1.5 vs. 2.0 days;1.0, 2.0; p = 0.003) or without (2.0; 1.0, 2.0 vs. 2.0 days; 2.0, 3.0; p = 0.024) hysterectomy, but no differences in OT, DeltaH, pain score, or narcotic use occurred. Posterior compartment mean pain scores were lower with Prolift (3.6 +/- 2.2 vs. 1.7 +/- 1.5, p = 0.035), and three-compartment-repair pain scores were lower with Elevate (0.6 +/- 1.3 vs 2.5 +/- 1.9; p = 0.013). Three bladder injuries occurred with Prolift but none with Elevate. CONCLUSIONS: Operative and postoperative experiences were similar between groups; however, Elevate anterior/apical repairs had shorter LOS, which might reflect more aggressive discharge planning. There were no bowel or major vascular injuries, and the Prolift trocar bladder injuries did not alter the surgical procedure. PMID- 22669428 TI - Does the G-spot exist? A review of the current literature. AB - In 1950, Grafenberg described a distinct erotogenic zone on the anterior wall of the vagina, which was referred to as the Grafenberg spot (G-spot) by Addiego, Whipple (a nurse) et al. in 1981. As a result, the G-spot has become a central topic of popular speculation and a basis of a huge business surrounding it. In our opinion, these sexologists have made a hotchpotch of Grafenberg's thoughts and ideas that were set forth and expounded in his 1950 article: the intraurethral glands are not the corpus spongiosum of the female urethra, and Grafenberg did not report an orgasm of the intraurethral glands. G-spot amplification is a cosmetic surgery procedure for temporarily increasing the size and sensitivity of the G-spot in which a dermal filler or a collagen-like material is injected into the bladder-vaginal septum. All published scientific data point to the fact that the G-spot does not exist, and the supposed G-spot should not be identified with Grafenberg's name. Moreover, G-spot amplification is not medically indicated and is an unnecessary and inefficacious medical procedure. PMID- 22669429 TI - Anisotropy in photocatalytic oxidization activity of NaNbO3 photocatalyst. AB - NaNbO(3) single-crystal films with (100), (110) and (111) oriented crystal planes were grown on LaAlO(3) (100), (110) and (111) substrates by pulsed laser deposition. The NaNbO(3) films exhibit anisotropy in the photocatalytic oxidization activity for Rhodamine B (RhB) degradation. The increasing order of RhB degradation in Ar atmosphere under full arc irradiation of a Xe lamp is (100) < (110) < (111), which is consistent with that of OH generation. The good linear relationship between the activity of RhB degradation and the coercive electric field indicates that the photocatalytic activity is closely related to the ferroelectric property. PMID- 22669430 TI - Margareta Ryberg (1946-2012): a personal tribute. AB - We pay tribute to the life and work of Margareta Ryberg (1946-2012). She was an expert on the different forms of protochlorophyll(ide), their protein partners, and their transformations in angiosperms; on the structural aspects, and the nature of prolamellar bodies, as well as on the localization of light-dependent NADPH:protochlorophyllide oxido-reductase. She was a great teacher, who also loved gardening and handicraft. But above all, she was a beloved wife, mother, grandmother, and friend who will be deeply missed. PMID- 22669431 TI - Toral lateral line units of goldfish, Carassius auratus, are sensitive to the position and vibration direction of a vibrating sphere. AB - We recorded the responses of lateral line units in the midbrain torus semicircularis of goldfish, Carassius auratus, to a 50-Hz vibrating sphere and determined the unit's spatial receptive fields for various distances between fish and sphere and for different directions of sphere vibration. All but one unit responded to the vibrating sphere with an increase in discharge rate. Only a proportion (25%) of the units exhibited phase-locked responses. Receptive fields were narrow or broad and contained one, two or more areas of increased discharge rate. The data show that the receptive fields of toral lateral line units are in many respects similar to those of brainstem units but differ from those of afferent nerve fibres. The responses of primary afferents represent the pressure gradient pattern generated by a vibrating sphere and provide information about sphere location and vibration direction. Across the array of lateral line neuromasts, the fish brain in principle can derive this information. Nevertheless, toral units tuned to a distinct sphere location or sensitive to a distinct sphere vibration direction were not found. Therefore, it is conceivable that the torus semicircularis uses a population code to determine spatial location and vibration direction of a vibrating sphere. PMID- 22669432 TI - Micro-scale fluid and odorant transport to antennules of the crayfish, Procambarus clarkii. AB - A numerical model was developed to determine advective-diffusive transport of odorant molecules to olfactory appendages of the crayfish, Procambarus clarkii. We tested the extent of molecule transport to the surfaces of aesthetasc sensilla during an antennule flick and the degree of odorant exchange during subsequent flicks. During the rapid downstroke of a flick, odorant molecules are advected between adjacent aesthetascs, while during the slower return stroke, these odorants are trapped between the sensilla and molecular diffusion occurs over a sufficient time period to transport odorants to aesthetasc surfaces. During subsequent flicks, up to 97.6% of these odorants are replaced with new odorant molecules. The concentration of molecules captured along aesthetasc surfaces was found to increase with increased gap spacing between aesthetascs, flick speed, and distance from the proximal end of the aesthetasc, but these changes in morphology and flicking kinematics reduce the animal's ability to take discrete samples of the odorant-laden fluid environment with each flick. Results suggest that antennule flicking allows discrete sampling of the time- and space-varying odorant signal, and high concentration odorant filaments can be distinguished from more diffuse, low concentration filaments through changes in both the timing and the encounter rate of odorant molecules to aesthetasc surfaces. PMID- 22669433 TI - [Botulinum toxin in the head and neck region]. PMID- 22669434 TI - [The application of botulinum toxin in oromandibular, pharyngeal and laryngeal dystonia]. AB - Dystonias of the oral, pharyngeal and laryngeal muscles are potential causes of deglutitive, respiratory and communicative disorders. In addition to functional deficits such as dysphagia, dysarthria and dysphonia, social disadvantages may arise from the visible or audible manifestations. Treatment with botulinum toxin offers symptomatic and temporary therapeutic effects. Examples of applications in oromandibular dystonia, palatoclonus, dysphagia and laryngeal dystonia (e.g., spasmodic dysphonia) are described. PMID- 22669435 TI - [Treatment of blepharospasm, hemifacial spasm and facial synkinesis with botulinum toxin]. AB - Involuntary facial movements are caused by various diseases. This article describes three of these diseases: blepharospasm, hemifacial spasm and facial synkinesis following facial nerve paralysis. The different etiologies, clinical symptoms and diagnosis are discussed. A common therapeutic approach for these three diseases is presented. Involuntary facial movements can be reduced or even completely suppressed by local injections of botulinum toxin. PMID- 22669436 TI - [Botulinum toxin for the treatment of secretory disorders of the head and neck area]. AB - Botulinum toxin can be used for the temporary blockade of secretory glands in the head and neck area. Botulinum toxin is increasingly the therapy of choice for the treatment of Frey's syndrome and gustatory tearing, and it is gaining attention for hypersalivation therapy. For nasal hypersecretion, this drug has a very specific use. In comparison to the treatment of skeletal muscles, the individual effect and its duration are more difficult to predict. All indications presented here are for off-label use; therefore, careful counseling and informed consent are necessary. With botulinum toxin, for several diseases, as new treatment options are opening up, well-founded knowledge about the indications and treatment course is important for the ENT surgeon. PMID- 22669437 TI - [Botulinum toxin type A for preventive treatment of chronic migraines]. AB - The use of botulinum toxin type A for chronic migraines was studied systematically in the PREEMPT trials program. Superiority to placebo treatment was established. Thus, for the first time a prophylactic drug against chronic migraines is available that is both effective and well tolerated. Botox(r) was licensed in England for the prophylaxis of headaches in adults with chronic migraines (headaches on at least 15 days per month of which at least 8 days are with migraines) in 2010. PMID- 22669439 TI - [Medical examination. Preparation for ENT specialisation. Part 5]. PMID- 22669438 TI - [Pharmacology of botulinum toxin drugs]. AB - Botulinum toxin (BT) is used with remarkable success to treat various disorders caused by muscle hyperactivities or exocrine gland overactivity. Its use for treatment of non-muscular pain conditions is currently being explored. In Germany, BT type A is available as Botox(r), Dysport(r) and Xeomin(r), BT type B as NeuroBloc(r). In aesthetic medicine they are called Vistabel(r), Azzalure(r) and Bocouture(r). Numerous other BT drugs are used worldwide. Often, their origin is dubious. BT drugs consist of botulinum neurotoxin, complexing proteins and adjuvants. Their manufacturing process is highly complex. BT drugs vary in many aspects. By no means are they generics. Clinically relevant differences include their potency labeling, antigenicity, presence of complexing proteins, storage conditions, pH value of the reconstituted drug and pharmaceutical preparation. PMID- 22669440 TI - [Guideline "Otitis media with effusion" - long version. S1 Guideline of the German Society of Otorhinolaryngology, Head and Neck Surgery]. PMID- 22669441 TI - Multidetector CT evaluation of various aortic diseases: diagnostic tips, pitfalls, and remedies for imaging artifacts. AB - With technical development of multidetector computed tomography (MDCT), diagnostic accuracy of CT in the evaluation of various aortic diseases has markedly increased. However, there are pitfalls that potentially hamper the proper diagnosis of aortic diseases with MDCT. Radiologists should recognize the various pitfalls and be familiar with the remedies of CT artifact occurring in patients with various aortic diseases. We describe prescriptions which allow prompt diagnosis and appropriate treatment for each aortic disease. PMID- 22669442 TI - Salvage liver transplantation for hepatic gas gangrene. AB - Hepatic gas gangrene is an uncommon situation mainly due to bacterial infection by Clostridium perfringens. It remains a life-threatening condition associated with a high mortality rate. Quick diagnosis and aggressive therapy including liver transplantation should be proposed to improve the outcome. This report describes a rare case of hepatic gas gangrene on native liver, secondary to iatrogenic hepatic artery thrombosis and instrumental biliary tree infection, which was successfully treated by liver transplantation. PMID- 22669443 TI - Anatomical study of the proximal origin of hamstring muscles. AB - PURPOSE: It is relatively well accepted that the long head of the biceps femoris and the semitendinosus both originate from the ischial tuberosity as a common tendon. However, it is also widely known that the biceps femoris is consistently injured more than the semitendinosus. The purpose of this study was to examine the origins of the hamstring muscles, to find an anatomic basis for diagnosis and treatment of injuries of the posterior thigh regions. MATERIALS AND METHODS: Twenty-eight hips of fourteen adult Japanese cadavers were used in this study. In twenty hips of ten cadavers, the positional relationships among the origins on the ischial tuberosity were examined. In eight hips of four cadavers, histological examination of the origins of the hamstrings was also performed. RESULTS: The origin of the long head of the biceps femoris adjoined that of the semitendinosus. In the proximal regions of these muscles, the long head consisted of the tendinous part; however, the semitendinosus mainly consisted of the muscular part. Some of the fibers of the biceps tendon extended to fuse with the sacrotuberous ligament. The semimembranosus muscle broadly originated from the lateral surface of the ischial tuberosity. CONCLUSION: The origins of the long head of the biceps femoris and the semitendinosus are found to be almost independent, and the tendon of the long head is partly fused with the sacrotuberous ligament. The high incidence of injuries to the long head of the biceps femoris could be explained by these anatomical configurations. PMID- 22669444 TI - Wound dehiscence and stump infection after lower limb amputation: risk factors and association with antibiotic use. AB - BACKGROUND: Optimal duration of antibiotic prophylaxis following major lower limb amputation in preventing adverse stump outcomes is controversial. OBJECTIVE: We assess the epidemiology and risk factors of wound dehiscence and stump infection after mid-thigh to transmetatarsal amputations with regard to antibiotic administration. METHODS: Our retrospective observational study at the Geneva University Hospital (January 1995-June 2010) includes a total of 289 amputations in 270 adult patients (199 males; median age 70 years). RESULTS: Wound dehiscence and/or stump infection occurred in 47 (16.3%) and 63 (21.8%) patients with a median delay of 24 and 14 days, respectively. No clinical variable was significantly associated with stump infection. Diabetes and older age (>80 years) were associated with dehiscence. Importantly, transcutaneous tissue oxygen tension (TcPO2) and duration of antibiotic administration showed no association with either outcome. CONCLUSION: The duration of antibiotic administration before or after surgery does not change the epidemiology of stump complications. PMID- 22669445 TI - Biomechanical comparison of two stabilization techniques for unstable sacral fractures. AB - AIM: The purpose of the study was to assess the stability provided by an ilio iliac dorsal plate fixation technique using an AO narrow DCP on the pelvic brim in vertically and rotationally unstable type-C pelvic ring injuries. MATERIALS AND METHODS: We examined 12 fresh cadaver pelvises in a single limb stance load. A type-C pelvic ring injury (a type I lateral sacral fracture in the classification of Denis with symphysis pubis rupture) was performed on the cadaver specimen and fixed with a four-hole narrow dynamic compression plate to stabilize the symphysis pubis rupture; the sacrum fracture was stabilized either anteriorly with two 3-hole reconstruction plates ("anterior plate osteosynthesis") or with a posterior fixation using a 12-hole narrow DCP. A cyclic load of between 100 and 250 N was applied to the fifth lumbar vertebra of the specimen. An extensometer was attached to both sides of the sacrum fracture to detect movements at the fracture site. RESULTS: We were able to achieve usable measurements in nine specimens. Three measurements were performed on each specimen, and the movements recorded at the fracture gap in trans-sacral plate fixation were higher than or similar to those observed for anterior plate synthesis in 23 out of 27 cases. CONCLUSION: Dorsal ilio-iliac bridge plate fixation provides somewhat reduced stability compared to anterior plate fixation, but the difference is not significant. PMID- 22669446 TI - Luteimicrobium album sp. nov., a novel actinobacterium isolated from a lichen collected in Japan, and emended description of the genus Luteimicrobium. AB - A novel Gram-stain-positive actinobacterium, designated RI148-Li105(T), was isolated from a lichen sample from Rishiri Island, Japan, and its taxonomic position was investigated by a polyphasic approach. 16S rRNA gene sequencing study indicated that strain RI148-Li105(T) was related to the type strain of Luteimicrobium subarcticum, with a similarity of 97.8%. Cells of strain RI148 Li105(T) exhibited a rod-coccus cycle. The diagnostic cell-wall diamino acid of this organism was lysine and the peptidoglycan type was found to be A4alpha. The predominant menaquinones were MK-8(H(2)) and MK-9(H(2)), and the major fatty acids were iso-C(16:0), C(17:1) omega9c and C(17:0). The DNA G+C content was 73.6 mol%. The major phenotypic characteristics of strain RI148-Li105(T) basically corresponded to those of the genus Luteimicrobium excluding the fatty acid composition. These results suggest that strain RI148-Li105(T) should be affiliated with the genus Luteimicrobium. Meanwhile, DNA-DNA hybridization and some phenotypic characteristics revealed that the strain differs from L. subarcticum. Therefore, strain RI148-Li105(T) represents a novel species of the genus Luteimicrobium, for which the name Luteimicrobium album sp. nov. is proposed. The type strain of Luteimicrobium album is RI148-Li105(T) (=NBRC 106348(T)=DSM 24866(T)). PMID- 22669447 TI - Pre-clinical pharmacokinetics and anti-chlamydial activity of salicylidene acylhydrazide inhibitors of bacterial type III secretion. AB - Salicylidene acylhydrazides belong to a class of compounds shown to inhibit bacterial type III secretion (T3S) in pathogenic Gram-negative bacteria. This class of compounds also inhibits growth and replication of Chlamydiae, strict intracellular bacteria that possess a T3S system. In this study a library of 58 salicylidene acylhydrazides was screened to identify inhibitors of Chlamydia growth. Compounds inhibiting growth of both Chlamydia trachomatis and Chlamydophila pneumoniae were tested for cell toxicity and seven compounds were selected for preliminary pharmacokinetic analysis in mice using cassette dosing. Two compounds, ME0177 and ME0192, were further investigated by individual pharmacokinetic analysis. Compound ME0177 had a relatively high peak plasma concentration (C(max)) and area under curve and therefore may be considered for systemic treatment of Chlamydia infections. The other compound, ME0192, had poor pharmacokinetic properties but the highest anti-chlamydial activity in vitro and therefore was tested for topical treatment in a mouse vaginal infection model. ME0192 administered vaginally significantly reduced the infectious burden of C. trachomatis and the number of infected mice. PMID- 22669448 TI - Surgical approach and outcomes in patients with lithium-associated hyperparathyroidism. AB - BACKGROUND: Patients receiving lithium therapy are at elevated risk of developing hyperparathyroidism. In lithium-associated hyperparathyroidism (LAH), the incidence of multiglandular disease (MGD) is unclear, and the need for routine bilateral cervical exploration remains controversial. Therefore, in LAH patients, surgical approaches, pathologic findings, cure rates, and factors associated with persistent or recurrent disease were investigated. METHODS: Retrospective analysis of 27 patients with LAH undergoing parathyroidectomy with the intraoperative parathyroid hormone (PTH) assay. RESULTS: The median postoperative follow-up was 7 months; 17 patients had >6 months follow-up. Cervical exploration was unilateral in 9, bilateral in 18 (3 were converted from unilateral). Sixteen patients (62%) had MGD, 12 with four-gland hyperplasia and 4 with double adenomas. Ten patients (38%) had a single adenoma. Twenty-five (93%) of 27 patients had initially successful surgery. Of the 17 patients with >6 months follow-up, two had persistent disease and two experienced recurrent disease. All patients with a single adenoma remain free of disease. Three (75%) of four patients with persistent/recurrent disease had MGD and were receiving lithium at the time of surgery. Patients with persistent/recurrent disease were older (p = 0.01) and had experienced a longer duration of hypercalcemia (p = 0.04). CONCLUSIONS: LAH patients have a high incidence of MGD, and bilateral exploration is frequently necessary. With access to the intraoperative PTH assay, it is reasonable to initiate a unilateral approach because many patients will harbor single adenomas and can be reliably rendered normocalcemic. Patients with MGD remain at higher risk of persistent/recurrent disease. PMID- 22669450 TI - Frequent and early death limits quality of life assessment in patients with advanced malignancies evaluated for palliative surgical intervention. AB - BACKGROUND: The purpose of this study was to determine the feasibility and optimal timing of quality of life assessment for patients undergoing palliative surgical evaluation. METHODS: Patients with an advanced malignancy undergoing consultation for palliative surgical intervention were prospectively enrolled from November 2009 to January 2011. Follow-up quality of life assessment was performed using validated instruments at 1 and 3 months post-enrollment. Univariate analysis of variables was performed to identify clinicopathologic variables associated with questionnaire completion. RESULTS: Of 77 patients enrolled, the most common clinical presentations included bowel obstruction (32 %), abdominal pain (21 %), wound complications (18 %), and gastrointestinal bleeding (11 %). Of the 77 patients, 34 (44 %) were treated with nonoperative/nonprocedural care, 9 (12 %) with endoscopic or interventional radiologic procedures, and 34 (44 %) with surgery. Follow-up questionnaires were obtained at 1 month and 3 months in 48 % and 15 %, respectively. A total of 31 patients (40 %) died prior to study completion. On univariate analysis, death was the only factor associated with questionnaire response. All other demographic, clinical, and treatment variables were not associated with response to questionnaires. There were no significant differences in baseline or follow-up quality of life scores between patients treated with surgical intervention or nonoperative management. CONCLUSIONS: Death during the study period was a significant factor in limiting adequate follow-up assessment. Future studies attempting to obtain follow-up data on patients evaluated for palliative surgical intervention may require larger patient numbers to account for frequent early death in this population and anticipate the need to account for the high rate of missing data in statistical analysis. PMID- 22669449 TI - The management of cervical lymph nodes in patients with cutaneous melanoma. AB - BACKGROUND: The aim of this study was to review the management of cervical lymph nodes in patients with cutaneous melanoma and to analyze factors influencing prognosis. METHODS: This was a retrospective cohort study of patients who had cervical node surgery at the Sydney Melanoma Unit from 1990 to 2004. RESULTS: Of 716 patients who met the study criteria, 339 had a sentinel node biopsy (SNB) and 396 had a neck dissection. Locoregional recurrence occurred in 27.6 % of those undergoing therapeutic neck dissection and 60 % eventually developed distant metastases. Radiotherapy was given as adjuvant treatment in 110 of the patients who had a therapeutic neck dissection (41 %), but this was not associated with improved regional control (p = .322). Multivariate analysis showed that nodal positivity (p < .001) and primary tumor ulceration (p = < .027) were the most important predictors of locoregional recurrence and that primary tumor Breslow thickness (p = .009) and node positivity (p = .046) were the most important factors predicting survival. SNB-positive patients who underwent immediate completion lymphadenectomy had a 5-year survival advantage over those who had a therapeutic neck dissection for macroscopic disease (54 % vs 47 %, p = .028). CONCLUSIONS: Nodal status was the most important factor predicting disease-free and overall survival in patients with melanoma of the head and neck. Adjuvant radiotherapy was not associated with better locoregional control in the non randomized cohorts of patients in this study. PMID- 22669451 TI - Recruitment of podoplanin positive cancer-associated fibroblasts in metastatic lymph nodes predicts poor prognosis in pathological N2 stage III lung adenocarcinoma. AB - BACKGROUND: Cancer-associated fibroblasts (CAFs) directly communicate with cancer cells and play important roles in cancer progression. Recent studies have reported that primary cancer tissue with podoplanin-expressing CAFs predicted a poorer outcome among stage I lung adenocarcinoma patients. However, whether podoplanin(+)-CAFs also can be recruited into metastatic lymph nodes and influence the prognosis remains unclear. METHODS: We selected 112 patients with pathological N2 stage III lung adenocarcinoma and examined the podoplanin expression of CAFs and their prognostic impact in primary and metastatic N2 lesions. RESULTS: Podoplanin(+)-CAFs were observed in 61 (54.5 %) primary sites and 44 (39.3 %) metastatic lymph nodes. Podoplanin(+)-CAFs were found at metastatic lymph nodes in 33 (54.1 %) primary podoplanin-positive and 11 (21.6 %) primary podoplanin-negative sites. These findings suggest a significant positive correlation in podoplanin expression in CAFs between pairs of primary and metastatic lesions (P < 0.001). The difference in the overall survival of patients with podoplanin-positive/negative CAFs in their primary lesion was not correlated (P = 0.927). In contrast, patients with podoplanin(+)-CAFs in metastatic lymph nodes had a shorter overall survival than those without podoplanin(+)-CAFs (P = 0.003). In multivariate analyses, podoplanin(+)-CAFs in metastatic lymph nodes were a significantly independent risk factor for a poor outcome (P = 0.007). CONCLUSIONS: Our study indicated that podoplanin(+)-CAFs in metastatic lymph nodes was a significant prognostic factor for overall survival among pathological N2 stage III adenocarcinoma patients. PMID- 22669452 TI - Society of Surgical Oncology Heritage Award: honoring William C. Wood, MD. PMID- 22669453 TI - Tumor budding is an independent predictor of outcome in AJCC/UICC stage II colorectal cancer. AB - BACKGROUND: In colorectal cancer, the morphology of the invasive tumor margin may reflect aggressiveness of tumor growth, thus providing important prognostic information. The tumor growth pattern according to Jass and the extent of tumor budding were analyzed in patients with American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) stage II disease. METHODS: Tumors of 120 randomly selected patients with AJCC/UICC stage II disease were retrospectively reviewed for tumor growth pattern (expanding vs. infiltrating) and the extent of tumor budding, with high-grade budding reflecting presence of 10 or more budding foci scattered at the invasive tumor margin. Progression-free and cancer-specific survivals were determined by the Kaplan-Meier method. For multivariable analysis, Cox's proportional hazards regression models were performed. RESULTS: The infiltrating growth pattern was significantly associated with histological subtype and lymphovascular invasion, while high-grade budding was significantly associated with tumor grade and lymphovascular invasion. High grade budding, but not the infiltrating growth pattern, was significantly associated with outcome in univariable analysis. Cox's proportional hazards regression models proved tumor budding to be an independent predictor of disease progression (hazard ratio 3.91, 95 % confidence interval 1.3-11.77; P = 0.02) and cancer-related death (hazard ratio 5.90, 95 % confidence interval 1.62-21.51; P = 0.007). The combination of infiltrating growth pattern and high-grade budding did not have a stronger prognostic significance than tumor budding alone. CONCLUSIONS: Tumor budding independently predicted patient outcome in patients with AJCC/UICC stage II colorectal cancer and may therefore be used for accurate prognostication, patient counseling, and design of clinical trials by using integrated multimodal therapy. PMID- 22669454 TI - Characteristic immunophenotype of solid subtype component in lung adenocarcinoma. AB - BACKGROUND: Lung adenocarcinomas represent a morphologically heterogeneous tumor composed of an admixture of different histologic subtypes (lepidic, papillary, acinar, and solid subtype). The presence of a solid subtype component is reported to be associated with a poorer prognosis. The aim of this study was to evaluate the characteristic immunophenotype of the solid subtype component compared with the immunophenotypes of other components. METHODS: We analyzed the clinicopathological characteristics of stage I adenocarcinoma patients with predominant solid subtype disease. Furthermore, we immunostained adenocarcinomas with predominant lepidic, papillary, acinar, and solid subtype components (n = 23 each) for 10 molecular markers of tumor invasiveness and scored the results. RESULTS: Patients showing predominance of the solid subtype component (solid subtype adenocarcinoma) had a poorer prognosis than those showing predominance of the lepidic, papillary, or acinar component. Lymphovascular invasion was more often detected in solid subtype tumors than in others. The solid subtype component showed a significantly stronger staining intensity of laminin-5 expression than the lepidic, papillary, and acinar components (P < 0.001, P < 0.001, and P = 0.016, respectively). The fibronectin and vimentin expression levels were also significantly higher in the solid subtype component than in other components. This immunostaining character was validated by using mixed subtype adenocarcinomas containing all four components in the same tumor. CONCLUSIONS: This study concluded that the solid subtype component in lung adenocarcinomas exhibit the invasive immunophenotype, including increased laminin 5 expression, compared with the other components, which may be associated with a poorer prognosis. PMID- 22669455 TI - Use of panitumumab-IRDye800 to image microscopic head and neck cancer in an orthotopic surgical model. AB - BACKGROUND: Fluorescence imaging hardware (SPY) has recently been developed for intraoperative assessment of blood flow via detection of probes emitting in the near-infrared (NIR) spectrum. This study sought to determine if this imaging system was capable of detecting micrometastatic head and neck squamous cell carcinoma (HNSCC) in preclinical models. METHODS: A NIR fluorescent probe (IRDye800CW) was covalently linked to a monoclonal antibody targeting epidermal growth factor receptor (EGFR; panitumumab) or nonspecific IgG. HNSCC flank (SCC 1) and orthotopic (FADU and OSC19) xenografts were imaged 48-96 h after systemic injection of labeled panitumumab or IgG. The primary tumor and regional lymph nodes were dissected using fluorescence guidance with the SPY system and grossly assessed with a charge-coupled NIR system (Pearl). Histologic slides were also imaged with a NIR charged-coupled device (Odyssey) and fluorescence intensity was correlated with pathologic confirmation of disease. RESULTS: Orthotopic tongue tumors were clearly delineated from normal tissue with tumor-to-background ratios of 2.9 (Pearl) and 2.3 (SPY). Disease detection was significantly improved with panitumumab-IRDye compared to IgG-IRDye800 (P < 0.05). Tissue biopsy samples (average size 3.7 mm) positive for fluorescence were confirmed for pathologic disease by histology and immunohistochemistry (n = 25 of 25). Biopsy samples of nonfluorescent tissue were proven to be negative for malignancy (n = 28 of 28). The SPY was able to detect regional lymph node metastasis (<1.0 mm) and microscopic areas of disease. Standard histological assessment in both frozen and paraffin-embedded histologic specimens was augmented using the Odyssey. CONCLUSIONS: Panitumumab-IRDye800 may have clinical utility in detection and removal of microscopic HNSCC using existing intraoperative optical imaging hardware and may augment analysis of frozen and permanent pathology. PMID- 22669456 TI - Comparison of radiogrammetrical metacarpal indices in children and reference data from the First Zurich Longitudinal Study. AB - BACKGROUND: A number of radiogrammetrical metacarpal indices are in use, some of which have been adapted for children. OBJECTIVE: The purpose of this study was to compare four known indices-bone mineral density (BMD), relative cortical area, Exton-Smith index, bending breaking resistance index-and the more recently defined pediatric bone index (PBI) according to the two criteria of minimum height dependence and minimum variability in children of equal bone age. MATERIALS AND METHODS: A total of 3,121 left-hand radiographs from 231 healthy Caucasian children ranging in age from 3 to 19 years old were analysed using BoneXpert(r), a programme for automatic analysis of hand radiographs and assessment of bone age. RESULTS: Dependence on height for chronological age or bone age and the mean relative standard deviation were lowest in the PBI for both genders pooled. The differences in height dependence were statistically significant and are shown to be clinically relevant. Reference data for PBI are presented. CONCLUSION: PBI may be a better indicator than BMD for bone health in children; however, verification in a clinical group is needed. PMID- 22669457 TI - Dose optimisation for intraoperative cone-beam flat-detector CT in paediatric spinal surgery. AB - BACKGROUND: During surgery for spinal deformities, accurate placement of pedicle screws may be guided by intraoperative cone-beam flat-detector CT. OBJECTIVE: The purpose of this study was to identify appropriate paediatric imaging protocols aiming to reduce the radiation dose in line with the ALARA principle. MATERIALS AND METHODS: Using O-arm(r) (Medtronic, Inc.), three paediatric phantoms were employed to measure CTDI(w) doses with default and lowered exposure settings. Images from 126 scans were evaluated by two spinal surgeons and scores were compared (Kappa statistics). Effective doses were calculated. The recommended new low-dose 3-D spine protocols were then used in 15 children. RESULTS: The lowest acceptable exposure as judged by image quality for intraoperative use was 70 kVp/40 mAs, 70 kVp/80 mAs and 80 kVp/40 mAs for the 1-, 5- and 12-year-old equivalent phantoms respectively (kappa = 0,70). Optimised dose settings reduced CTDI(w) doses 89-93%. The effective dose was 0.5 mSv (91-94,5% reduction). The optimised protocols were used clinically without problems. CONCLUSIONS: Radiation doses for intraoperative 3-D CT using a cone-beam flat-detector scanner could be reduced at least 89% compared to manufacturer settings and still be used to safely navigate pedicle screws. PMID- 22669458 TI - The creation of non-disease: an assault on the diagnosis of child abuse. PMID- 22669460 TI - XBP1S protects cells from ER stress-induced apoptosis through Erk1/2 signaling pathway involving CHOP. AB - The mammalian unfolded protein response (UPR) protects the cell against the stress of misfolded proteins in the endoplasmic reticulum (ER), and the transcription factor X-box binding protein 1 spliced (XBP1S), a regulator of the UPR, is known to be important for ER stress (ERS)-mediated apoptosis and cell growth, but the molecular mechanism underlying these processes remains unexplored. Here, we report that knockdown of XBP1S by an siRNA silencing approach increased the expression of ERS-associated molecules. The overexpression of XBP1S stimulated, whereas its knockdown inhibited, cell proliferation in chondrocytes and chondrosarcoma cells; in addition, overexpression of XBP1S inhibited, while its repression enhanced, ERS-mediated apoptosis in chondrocytes and chondrosarcoma cells. Furthermore, XBP1S-mediated inhibition of apoptosis in response to ERS is through the Erk1/2 signaling pathway and down-regulation CHOP transcription factor. CHOP is one of the key downstream molecules known to be involved in ERS-mediated apoptosis. Collectively, these findings reveal a novel critical role of XBP1S in ERS-mediated apoptosis and the molecular mechanisms involved. PMID- 22669459 TI - Lamins at a glance. PMID- 22669461 TI - Divergent regulation of Wnt-mediated development of the dorsomedial and ventrolateral dermomyotomal lips. AB - The dermomyotome is the dorsal compartment of the somite which gives rise to multiple cell fates including skeletal muscle, connective tissue, and endothelia. It consists of a pseudostratified, roughly rectangular epithelial sheet, the margins of which are called the dermomyotomal lips. The dermomyotomal lips are blastema-like epithelial growth zones, which continuously give rise to resident dermomyotomal cells and emigrating muscle precursor cells, which populate the subjacent myotomal compartment. Wnt signaling has been shown to regulate both dermomyotome formation and maintenance of the dermomyotomal lips. Whereas the epithelialization of the dermomyotome is regulated via canonical, beta-catenin dependent Wnt signaling, the downstream signaling mechanisms suppressing epithelial-mesenchymal transition (EMT) in the mature dermomyotomal lips have been unknown. Here, we present evidence that dermomyotomal lip sustainment is differentially regulated. Whereas the dorsomedial dermomyotomal lip is maintained by canonical Wnt signaling, development of the ventrolateral dermomyotomal lip is regulated by non-canonical, PCP-like Wnt signaling. We discuss our results in the light of the different developmental prerequisites in the dorsomedial and ventrolateral lips, respectively, thus providing a new perspective on the regulation of dermomyotomal EMT. PMID- 22669463 TI - Identification of amino acids involved in catalytic process of M. tuberculosis GlmU acetyltransferase. AB - M. tuberculosis GlmU is a bifunctional enzyme with acetyltransferase activity in C-terminus and uridyltransferase activity in N-terminus, and it is involved in the biosynthesis of glycosyl donor UDP-N-acetylglucosamine (UDP-GlcNAc). The crystal structure of M. tuberculosis GlmU clearly determines the active site and catalytic mechanism of GlmU uridyltransferase domain but not succeed in GlmU acetyltransferase domain. Sequence comparison analysis revealed highly conserved amino acid residues in the C-terminus between M. tuberculosis GlmU and GlmU enzymes from other bacteria. To find the essential amino acids related to M. tuberculosis GlmU acetyltransferase activity, we substituted 10 conserved amino acids in the acetyltransferase domain of M. tuberculosis GlmU by site-directed mutagenesis. All the mutant GlmU proteins were largely expressed in soluble and purified by affinity chromatography. Enzyme assays showed that K362A, H374A, Y398A and W460A mutants abolished more than 90% activity of M. tuberculosis GlmU acetyltransferase and totally lost the affinity with two substrates, suggesting the potential substrate-binding functions. However, K403A, S416A, N456A and E458A mutants exhibited decreased GlmU acetyltransferase activity and lower kinetic parameters, probably responsible for substrate releasing by conformation shifting. PMID- 22669462 TI - Carbohydrate-based cancer vaccines: target cancer with sugar bullets. AB - With the booming development of glycobiology and glycochemistry, more and more structures of tumor-associated carbohydrate antigens (TACAs) are identified. Their broad expression and high specificity in cancer make them important targets to develop cancer vaccines or immunotherapies. However, most of the TACAs are T cell-independent antigens, they cannot elicit a powerful enough immune response to prevent or treat cancer. Immunotolerance and immunosuppression are more easily induced due to their endogenous properties and the declining immunity of the patients. This review summarizes the recent efforts to overcome these obstacles: coupling the carbohydrate antigens to proper carriers such as proteins or some small molecule carriers, and chemically modifying the structures of the TACAs to enhance the immunogenicity of TACAs and break the immunotolerance. PMID- 22669464 TI - Happiness and job satisfaction in a casino-dominated economy. AB - Proposals for casinos usually focus on numbers of jobs without considering their quality. We surveyed 1,506 Macau residents, modelling happiness and job satisfaction. Being employed is shown to be important for 'happiness'. But job attributes also matter, confirming the work domain as influential on wellbeing. Casino employees report similar happiness as others. However, despite relatively high pay, they report low overall job satisfaction. The particular aspects of their jobs that they rated generally negatively tended to be those inherent in casino employment rather than easily modifiable by managerial action. PMID- 22669465 TI - Personal glucose sensor for point-of-care early cancer diagnosis. AB - Early POC diagnosis of cancer is demonstrated by using multi-invertase conjugated microsphere labels and a personal glucose sensor (PGS) transducer. The invertase, which catalyzes the hydrolysis of sucrose to glucose, enables the PGS to detect target analytes beyond glucose, and the numerous invertase labels involved in each antibody-antigen binding event lead to significantly amplified PGS readings for sensitive protein detection. PMID- 22669466 TI - The B-cell identity factor Pax5 regulates distinct transcriptional programmes in early and late B lymphopoiesis. AB - Pax5 controls the identity and development of B cells by repressing lineage inappropriate genes and activating B-cell-specific genes. Here, we used genome wide approaches to identify Pax5 target genes in pro-B and mature B cells. In these cell types, Pax5 bound to 40% of the cis-regulatory elements defined by mapping DNase I hypersensitive (DHS) sites, transcription start sites and histone modifications. Although Pax5 bound to 8000 target genes, it regulated only 4% of them in pro-B and mature B cells by inducing enhancers at activated genes and eliminating DHS sites at repressed genes. Pax5-regulated genes in pro-B cells account for 23% of all expression changes occurring between common lymphoid progenitors and committed pro-B cells, which identifies Pax5 as an important regulator of this developmental transition. Regulated Pax5 target genes minimally overlap in pro-B and mature B cells, which reflects massive expression changes between these cell types. Hence, Pax5 controls B-cell identity and function by regulating distinct target genes in early and late B lymphopoiesis. PMID- 22669467 TI - Female parthenogenetic apomixis and androsporogenetic parthenogenesis in embryonal cells of Araucaria angustifolia: interpolation of progenesis and asexual heterospory in an artificial sporangium. AB - Cell fate, development timing and occurrence of reproductive versus apomictic development in gymnosperms are shown to be influenced by culture conditions in vitro. In this study, female parthenogenetic apomixis (fPA), androsporogenetic parthenogenesis (mAP) and progenesis were demonstrated using embryonal initials of Araucaria angustifolia in scaled-up cell suspensions passing through a single cell bottleneck in darkness and in an artificial sporangium (AS). Expression was based on defined nutrition, hormones and feedforward-adaptive feedback process controls at 23-25 degrees C and in darkness. In fPA, the nucleus of an embryonal initial undergoes endomitosis and amitosis, forming a diploid egg-equivalent and an apoptotic ventral canal nucleus in a transdifferentiated archegonial tube. Discharge of egg-equivalent cells as parthenospores and their dispersal into the aqueous culture medium were followed by free-nuclear conifer-type proembryogenesis. This replaced the plesiomorphic and central features of proembryogenesis in Araucariaceae. Protoplasmic fusions of embryonal initials were used to reconstruct heterokaryotic expressions of fPA in multiwell plates. In mAP, restitutional meiosis (automixis) was responsible for androsporogenesis and the discharge of monads, dyads, tetrads and polyads. In a display of progenesis, reproductive development was brought to an earlier ontogenetic stage and expressed by embryonal initials. Colchicine increased polyploidy, but androspore formation became aberrant and fragmented. Aberrant automixis led to the formation of chromosomal bouquets, which contributed to genomic silencing in embryonal initials, cytomixis and the formation of pycnotic micronucleated cells. Dispersal of female and male parthenospores displayed heteromorphic asexual heterospory in an aqueous environment. PMID- 22669468 TI - Undercarboxylated osteocalcin is positively associated with free testosterone in male patients with type 2 diabetes mellitus. AB - Although a recent study showed that undercarboxylated osteocalcin (ucOC) is important for male fertility and testosterone production by testes, little is known about the relationship between ucOC and testosterone in humans. We found for the first time that ucOC is positively associated with free testosterone in men with type 2 diabetes. INTRODUCTION: The ucOC has been shown to play a key role in energy metabolism as an endocrine hormone. Although a recent animal study demonstrated that ucOC is also important for male fertility and testosterone production by the testes, association between serum osteocalcin and testosterone levels has not been understood in humans. METHODS: Sixty-nine male patients with type 2 diabetes were recruited and chemical bone markers [total osteocalcin (TOC), ucOC, bone-specific alkaline phosphatase (BAP), and urinary N-terminal cross-linked telopeptide of type I collagen (uNTX)], gonadotropic hormones [luteinizing hormone (LH) and follicle-stimulating hormone (FSH)], and free testosterone (FT) were measured. RESULTS: Multiple regression analysis showed that ucOC and ucOC/TOC ratio were associated positively with FT and negatively with LH (for ucOC, beta = 0.30, p = 0.042 and beta = -0.52, p = 0.048; for ucOC/TOC ratio, beta = 0.31, p = 0.031 and beta = -0.54, p = 0.036, respectively) independently of age, duration of diabetes, body mass index, and hemoglobin A1c. ucOC and ucOC/TOC ratio were significantly associated with FT even after adjusting for LH and FSH (beta = 0.24, p = 0.042 and beta = 0.25, p = 0.031, respectively). However, neither TOC, BAP, nor uNTX was associated with the gonadotropic hormones or FT levels. CONCLUSIONS: The present study indicates for the first time that ucOC is associated positively with FT and negatively with LH in type 2 diabetes. These findings support the recent evidence that ucOC is involved in testosterone production in male subjects. PMID- 22669470 TI - Bimetallic coordination networks based on Al(acacCN)3: a building block between inertness and lability. AB - The Al(III) complex of 3-cyanopentane-2,4-dionate (acacCN) features peripheric nitrile groups which may coordinate to silver cations. As the Al(acacCN)(3) building block ranges between inertness and lability, its reactivity towards Ag(I) salts depends on the solvent and the weakly or non-coordinating counter anions; an impressive range of different extended structures has been encountered. With AgPF(6), the original building block is retained and hexafluorophosphate remains uncoordinated. A highly symmetric 3D crystalline solid forms in the presence of trichloromethane, and with benzene a tetrasolvate with large solvent-filled voids is obtained. Two different classes of reaction products with silver triflate have been observed. In addition to networks incorporating Al(acacCN)(3), partial solvolysis may lead to a dinuclear methoxide bridged derivative. The resulting Al(2)(MU-OMe)(2) core may be perceived as a four-connected node in a self-interpenetrating 3D network. Earlier studies reported transmetalation for the reaction of Al(acacCN)(3) with AgNO(3) and we find the same reactivity for silver tetrafluoroborate. Full degradation of the Al(III) building block with formation of [Ag(acacCN)] is observed. PMID- 22669469 TI - Fractures in users of antidepressants and anxiolytics and sedatives: effects of age and dose. AB - SUMMARY: Antidepressants have been associated with fractures. In a case-control study, increasing age was associated with more fractures in users of selective serotonin reuptake inhibitors and tricyclic antidepressants, whereas for anxiolytics and sedatives, more fractures were seen among the younger users. Depression per se did not seem associated with fractures. INTRODUCTION: This study aims to study the effects of age and dose of selective serotonin reuptake inhibitors (SSRI), tricyclic antidepressants (TCA) and anxiolytics/sedatives on fracture risk. METHODS: The study was designed as a case-control study. From the Danish National Health Service, we identified 124,655 fracture cases and 373,962 age- and gender-matched controls. Crude odds ratios were estimated, and propensity score adjustment was used to minimise confounding by indication. RESULTS: A higher risk of fractures was associated with an increasing dose of anxiolytics and sedatives; the highest excess risk was present in the age stratum below 40 years of age (p < 0.01), and thereafter, the excess risk of fractures declined with age. For SSRI, a growing excess risk of fractures was seen with both increasing dose and age. Regarding TCA, no particular trend with age was present. However, an increasing risk of fractures was associated with increasing TCA dose in the age group above 60 years. Finally, for other antidepressants, no particular trend with age or dose was observed. In our data, a hospital diagnosis of depression or manic depression was associated with fewer fractures. CONCLUSION: Caution should be shown upon prescription of SSRI to older subjects. A hospital diagnosis of depression or manic depression and thus potentially a more severe disease was not a risk factor for fractures. PMID- 22669471 TI - Sleep disturbances in adult survivors of childhood brain tumors. AB - PURPOSE: The aims of this study are to compare self-reported sleep quality in adult survivors of childhood brain tumors and a population-based comparison group, to identify treatment-related factors associated with sleep disturbances, and to identify the impact of post-treatment obesity and depression on sleep scores in adult survivors of childhood brain tumors. METHODS: Randomly selected adult survivors of childhood brain tumors (n = 78) and age-, sex-, and zip code matched population-group members (n = 78) completed the Pittsburgh Sleep Quality Index and the Brief Symptom Inventory. Sleep quality and the effect of demographic, treatment, and post-treatment characteristics were evaluated with linear and logistic regression analyses. RESULTS: Brain tumor survivors were 2.7 (95% CI, 1.1, 6.5) times more likely than the comparison group to take greater than 30 min to fall asleep. Females in both groups reported worse sleep quality and impaired daytime functioning. Among survivors, post-treatment obesity was associated with daytime dysfunction. CONCLUSIONS: These results agree with previous studies associating sleep, sex, and obesity and identified longer sleep latency as being a problem among childhood brain tumor survivors. Further study identifying factors contributing to sleep latency, and its impact on quality of life among adult survivors of childhood brain tumors is needed. PMID- 22669472 TI - Prognostic value of quality of life measured after treatment on subsequent survival in patients with nasopharyngeal carcinoma. AB - PURPOSE: Pretreatment quality of life (QoL) has been used to predict survival in cancer patients. In this study, we examined the prognostic value of QoL measured after treatment on subsequent survival in patients with nasopharyngeal carcinoma (NPC). METHODS: We enrolled 273 patients with NPC who had been curatively treated for more than 1 year. The EORTC QLQ-C30 and H&N35 questionnaires were completed 1 year after radiotherapy. The predictability of QoL variables on disease-specific survival (DSS) and overall survival (OS) was analyzed using Cox's proportional hazards models. RESULTS: Twenty-nine (10.6%) patients developed locoregional relapse and 27 (9.9%) had distant metastasis after the QoL survey with subsequent 5-year DSS and OS rates of 87.9% and 84.0 %, respectively. Based on the QLQ-C30, scales of physical functioning, fatigue, and appetite loss significantly predicted DSS and OS (p < 0.05). In the H&N35, only sexuality was significantly correlated with DSS and OS (p < 0.05). An increment of 10 points in physical functioning (HR: 0.69; 95% CI: 0.48-0.90; p = 0.004) or a decline of 10 points in fatigue problems (HR: 1.40; 95% CI: 1.19-1.61; p = 0.0002), appetite loss (HR: 1.21; 95% CI: 1.03-1.40; p = 0.02), and sexuality (HR: 1.14; 95% CI: 1.02-1.25; p = 0.019) was associated with better OS. CONCLUSION: Some QoL variables measured after the treatment provide prognostic value on subsequent survival in patients with NPC. PMID- 22669473 TI - Common variants of the genes encoding erythropoietin and its receptor modulate cognitive performance in schizophrenia. AB - Erythropoietin (EPO) improves cognitive performance in clinical studies and rodent experiments. We hypothesized that an intrinsic role of EPO for cognition exists, with particular relevance in situations of cognitive decline, which is reflected by associations of EPO and EPO receptor (EPOR) genotypes with cognitive functions. To prove this hypothesis, schizophrenic patients (N > 1000) were genotyped for 5' upstream-located gene variants, EPO SNP rs1617640 (T/G) and EPORSTR(GA)(n). Associations of these variants were obtained for cognitive processing speed, fine motor skills and short-term memory readouts, with one particular combination of genotypes superior to all others (p < 0.0001). In an independent healthy control sample (N > 800), these associations were confirmed. A matching preclinical study with mice demonstrated cognitive processing speed and memory enhanced upon transgenic expression of constitutively active EPOR in pyramidal neurons of cortex and hippocampus. We thus predicted that the human genotypes associated with better cognition would reflect gain-of-function effects. Indeed, reporter gene assays and quantitative transcriptional analysis of peripheral blood mononuclear cells showed genotype-dependent EPO/EPOR expression differences. Together, these findings reveal a role of endogenous EPO/EPOR for cognition, at least in schizophrenic patients. PMID- 22669474 TI - Examination of the cytotoxic and embryotoxic potential and underlying mechanisms of next-generation synthetic trioxolane and tetraoxane antimalarials. AB - Semisynthetic artemisinin-based therapies are the first-line treatment for P. falciparum malaria, but next-generation synthetic drug candidates are urgently required to improve availability and respond to the emergence of artemisinin resistant parasites. Artemisinins are embryotoxic in animal models and induce apoptosis in sensitive mammalian cells. Understanding the cytotoxic propensities of antimalarial drug candidates is crucial to their successful development and utilization. Here, we demonstrate that, similarly to the model artemisinin artesunate (ARS), a synthetic tetraoxane drug candidate (RKA182) and a trioxolane equivalent (FBEG100) induce embryotoxicity and depletion of primitive erythroblasts in a rodent model. We also show that RKA182, FBEG100 and ARS are cytotoxic toward a panel of established and primary human cell lines, with caspase-dependent apoptosis and caspase-independent necrosis underlying the induction of cell death. Although the toxic effects of RKA182 and FBEG100 proceed more rapidly and are relatively less cell-selective than that of ARS, all three compounds are shown to be dependent upon heme, iron and oxidative stress for their ability to induce cell death. However, in contrast to previously studied artemisinins, the toxicity of RKA182 and FBEG100 is shown to be independent of general chemical decomposition. Although tetraoxanes and trioxolanes have shown promise as next-generation antimalarials, the data described here indicate that adverse effects associated with artemisinins, including embryotoxicity, cannot be ruled out with these novel compounds, and a full understanding of their toxicological actions will be central to the continuing design and development of safe and effective drug candidates which could prove important in the fight against malaria. PMID- 22669477 TI - Molecular diversity, metabolic transformation, and evolution of carotenoid feather pigments in cotingas (Aves: Cotingidae). AB - Carotenoid pigments were extracted from 29 feather patches from 25 species of cotingas (Cotingidae) representing all lineages of the family with carotenoid plumage coloration. Using high-performance liquid chromatography (HPLC), mass spectrometry, chemical analysis, and 1H-NMR, 16 different carotenoid molecules were documented in the plumages of the cotinga family. These included common dietary xanthophylls (lutein and zeaxanthin), canary xanthophylls A and B, four well known and broadly distributed avian ketocarotenoids (canthaxanthin, astaxanthin, alpha-doradexanthin, and adonixanthin), rhodoxanthin, and seven 4 methoxy-ketocarotenoids. Methoxy-ketocarotenoids were found in 12 species within seven cotinga genera, including a new, previously undescribed molecule isolated from the Andean Cock-of-the-Rock Rupicola peruviana, 3'-hydroxy-3-methoxy beta,beta-carotene-4-one, which we name rupicolin. The diversity of cotinga plumage carotenoid pigments is hypothesized to be derived via four metabolic pathways from lutein, zeaxanthin, beta-cryptoxanthin, and beta-carotene. All metabolic transformations within the four pathways can be described by six or seven different enzymatic reactions. Three of these reactions are shared among three precursor pathways and are responsible for eight different metabolically derived carotenoid molecules. The function of cotinga plumage carotenoid diversity was analyzed with reflectance spectrophotometry of plumage patches and a tetrahedral model of avian color visual perception. The evolutionary history of the origin of this diversity is analyzed phylogenetically. The color space analyses document that the evolutionarily derived metabolic modifications of dietary xanthophylls have resulted in the creation of distinctive orange-red and purple visual colors. PMID- 22669475 TI - Heat shock protein 70: roles in multiple sclerosis. AB - Heat shock proteins (HSP) have long been considered intracellular chaperones that possess housekeeping and cytoprotective functions. Consequently, HSP overexpression was proposed as a potential therapy for neurodegenerative diseases characterized by the accumulation or aggregation of abnormal proteins. Recently, the discovery that cells release HSP with the capacity to trigger proinflammatory as well as immunoregulatory responses has focused attention on investigating the role of HSP in chronic inflammatory autoimmune diseases such as multiple sclerosis (MS). To date, the most relevant HSP is the inducible Hsp70, which exhibits both cytoprotectant and immunoregulatory functions. Several studies have presented contradictory evidence concerning the involvement of Hsp70 in MS or experimental autoimmune encephalomyelitis (EAE), the MS animal model. In this review, we dissect the functions of Hsp70 and discuss the controversial data concerning the role of Hsp70 in MS and EAE. PMID- 22669476 TI - IPLEX administration improves motor neuron survival and ameliorates motor functions in a severe mouse model of spinal muscular atrophy. AB - Spinal muscular atrophy (SMA) is an inherited neurodegenerative disorder and the first genetic cause of death in childhood. SMA is caused by low levels of survival motor neuron (SMN) protein that induce selective loss of alpha-motor neurons (MNs) in the spinal cord, resulting in progressive muscle atrophy and consequent respiratory failure. To date, no effective treatment is available to counteract the course of the disease. Among the different therapeutic strategies with potential clinical applications, the evaluation of trophic and/or protective agents able to antagonize MNs degeneration represents an attractive opportunity to develop valid therapies. Here we investigated the effects of IPLEX (recombinant human insulinlike growth factor 1 [rhIGF-1] complexed with recombinant human IGF-1 binding protein 3 [rhIGFBP-3]) on a severe mouse model of SMA. Interestingly, molecular and biochemical analyses of IGF-1 carried out in SMA mice before drug administration revealed marked reductions of IGF-1 circulating levels and hepatic mRNA expression. In this study, we found that perinatal administration of IPLEX, even if does not influence survival and body weight of mice, results in reduced degeneration of MNs, increased muscle fiber size and in amelioration of motor functions in SMA mice. Additionally, we show that phenotypic changes observed are not SMN-dependent, since no significant SMN modification was addressed in treated mice. Collectively, our data indicate IPLEX as a good therapeutic candidate to hinder the progression of the neurodegenerative process in SMA. PMID- 22669478 TI - Increase of 20-HETE synthase after brain ischemia in rats revealed by PET study with 11C-labeled 20-HETE synthase-specific inhibitor. AB - 20-Hydroxyeicosatetraenoic acid (20-HETE), an arachidonic acid metabolite known to be produced after cerebral ischemia, has been implicated in ischemic and reperfusion injury by mediating vasoconstriction. To develop a positron emission tomography (PET) probe for 20-HETE synthase imaging, which might be useful for monitoring vasoconstrictive processes in patients with brain ischemia, we synthesized a (11)C-labeled specific 20-HETE synthase inhibitor, N'(4 dimethylaminohexyloxy)phenyl imidazole ([(11)C]TROA). Autoradiographic study showed that [(11)C]TROA has high-specific binding in the kidney and liver consistent with the previously reported distribution of 20-HETE synthase. Using transient middle cerebral artery occlusion in rats, PET study showed significant increases in the binding of [(11)C]TROA in the ipsilateral hemisphere of rat brains after 7 and 10 days, which was blocked by co-injection of excess amounts of TROA (10 mg/kg). The increased [(11)C]TROA binding on the ipsilateral side returned to basal levels within 14 days. In addition, quantitative real-time PCR revealed that increased expression of 20-HETE synthase was only shown on the ipsilateral side on day 7. These results indicate that [(11)C]TROA might be a useful PET probe for imaging of 20-HETE synthase in patients with cerebral ischemia. PMID- 22669479 TI - Penumbra detection using PWI/DWI mismatch MRI in a rat stroke model with and without comorbidity: comparison of methods. AB - Perfusion-diffusion (perfusion-weighted imaging (PWI)/diffusion-weighted imaging (DWI)) mismatch is used to identify penumbra in acute stroke. However, limitations in penumbra detection with mismatch are recognized, with a lack of consensus on thresholds, quantification and validation of mismatch. We determined perfusion and diffusion thresholds from final infarct in the clinically relevant spontaneously hypertensive stroke-prone (SHRSP) rat and its normotensive control strain, Wistar-Kyoto (WKY) and compared three methods for penumbra calculation. After permanent middle cerebral artery occlusion (MCAO) (WKY n=12, SHRSP n=15), diffusion-weighted (DWI) and perfusion-weighted (PWI) images were obtained for 4 hours post stroke and final infarct determined at 24 hours on T(2) scans. The PWI/DWI mismatch was calculated from volumetric assessment (perfusion deficit volume minus apparent diffusion coefficient (ADC)-defined lesion volume) or spatial assessment of mismatch area on each coronal slice. The ADC-derived lesion growth provided the third, retrospective measure of penumbra. At 1 hour after MCAO, volumetric mismatch detected smaller volumes of penumbra in both strains (SHRSP: 31 +/- 50 mm(3), WKY: 22 +/- 59 mm(3), mean +/- s.d.) compared with spatial assessment (SHRSP: 36 +/- 15 mm(3), WKY: 43 +/- 43 mm(3)) and ADC lesion expansion (SHRSP: 41 +/- 45 mm(3), WKY: 65 +/- 41 mm(3)), although these differences were not statistically significant. Spatial assessment appears most informative, using both diffusion and perfusion data, eliminating the influence of negative mismatch and allowing the anatomical location of penumbra to be assessed at given time points after stroke. PMID- 22669480 TI - Alterations of the Hsp70/Hsp90 chaperone and the HOP/CHIP co-chaperone system in cancer. AB - Activation of the Hsp90 chaperone system is a characteristic of cancer cells. The regulation of chaperone activities involves their interaction with cochaperones; therefore we investigated the expression of Hsp70 and Hsp90 and their specific co chaperones HOP and CHIP in cancer cell lines and primary cancers. Inhibition of Hsp90 by 17AAG increased the levels of Hsp70, Hsp90 and HOP but not CHIP mRNA in cancer cells. These changes are linked to activation of the HSF1 transcription factor and we show that the HOP promoter contains HSF1 binding sites, and that HSF1 binding to the HOP promoter is increased following 17AAG. The lack of alteration in the co-chaperone CHIP is explained by a lack of HSF response elements in the CHIP promoter. Non-proliferating cells expressed higher levels of CHIP and lower HOP, Hsp70 and Hsp90 levels compared to proliferating cells. Decreased expression of CHIP in proliferating cancer cells is in keeping with its proposed tumor suppressor properties, while over-expression of HOP in proliferating cells may contribute to excessive Hsp90 activity and stabilization of client proteins in tumors. In a panel of colorectal cancer samples, increased expression of Hsp70 and an increased ratio of HOP to CHIP were found, and were associated with decreased median survival. These data indicate that multiple changes occur in the chaperone/co-chaperone system in cancer that impact patient survival. It is likely that the ability to identify individual alterations to this system will be beneficial for treatment strategy decisions, particularly those that employ chaperone inhibitors. PMID- 22669481 TI - De novo synthesis of protein phosphatase 1A, magnesium dependent, alpha isoform (PPM1A) during oocyte maturation. AB - Oocyte maturation in mammals is a multiple-stage process that generates fertilizable oocytes. Ovarian oocytes are arrested at prophase of the first meiotic division characterized by the presence of a germinal vesicle. Towards ovulation, the oocytes resume meiosis and proceed to the second metaphase in a process known as maturation; they undergo nuclear and cytoplasmic changes that are accompanied by translation and degradation of mRNA. Protein phosphatase 1A, magnesium dependent, alpha isoform (PPM1A), which belongs to the metal-dependent serine/threonine protein phosphatase family, is highly conserved during evolution. PPM1A plays a significant role in many cellular functions such as cell cycle progression, apoptosis and cellular differentiation. It works through diverse signaling pathways, including p38 MAP kinase JNK and transforming growth factor beta (TGF-beta). Herein we report that PPM1A is expressed in mouse oocytes and that its mRNA level rises during oocyte maturation. Using quantitative real time polymerase chain reaction (qPCR) and western blot analysis, we found that PPM1A mRNA is synthesized at the beginning of the maturation process and remains elevated in the mature oocytes, promoting the accumulation of PPM1A protein. Since PPM1A function is mainly affected by its level, we propose that it might have an important role in oocyte maturation. PMID- 22669483 TI - Long-term results of single intradermal 1 % methylene blue injection for intractable idiopathic pruritus ani: a prospective study. AB - BACKGROUND: The aim of this study was to assess the effectiveness and side effects of methylene blue injection into the perianal skin of patients with chronic refractory idiopathic pruritus ani (IPA). METHODS: Patients with IPA who failed to respond to standard perianal skin care advice and treatment of associated pathologies were included. One per cent methylene blue solution was injected intradermally into the itching perianal area up to the level of the dentate line, with a 10-ml syringe with a 22-gauge needle, using a total of 15 ml. A patient symptom score from 1 to 5 was used (1 = worst). The study was designed as a single-centre, prospective, non-randomized trial. RESULTS: Between September 2004 and November 2008, 10 patients with IPA were included in the study. Symptoms resolved within 4 weeks in all cases. Numbness of the perianal area and tattooing disappeared within the period of 3-4 weeks. There was no skin necrosis or anaphylaxis. The median follow-up was 47 months, range 29-60 months. Anal itching recurred in 8 patients. Four of those 8 patients noted that anal itching was less severe when it recurred, and it was unchanged in the other 4 patients. Six out of 10 patients felt much better or reported the resolution of pruritus ani. CONCLUSIONS: An intradermal application of 1 % methylene blue solution is associated with a positive effect on IPA with mild side effects related to sensory cutaneous innervation in all patients within the first 4 weeks following the procedure and a 20 % success rate within 60 months. PMID- 22669482 TI - Analgesia without sedatives during colonoscopies: worth considering? AB - Colonoscopy is a proven method for bowel cancer screening and is often experienced as a painful procedure. Today, there are two main strategies to facilitate colonoscopy. First, deep sedation results in satisfied patients but increases sedation-associated risks and raises costs for healthcare providers. Second, there is the advocacy for colonoscopies without any form of sedation. This might be an option for a special group of patients, but does not hold true for everybody. Following Moerman's hypothesis: "If pain is the crucial point, why do we need sedation?" this review shows the analgesic options for a painless procedure, increasing success rates without increasing risk of sedation. There are two agents, with the potential to be a nearly ideal analgesic agent for colonoscopy: alfentanil and nitrous oxide (N(2)O). Administration of either substance causes the patient to be comfortable yet alert and facilitates a short turnover. Advantages of these drugs include rapid onset and offset of action, analgesic and anxiolytic effects, ease of titration to desired level, rapid recovery, and an excellent safety profile. PMID- 22669484 TI - A retrospective comparison of the location and diameter of the inferior alveolar canal at the mental foramen and length of the anterior loop between American and Taiwanese cohorts using CBCT. AB - PURPOSE: The aim was to retrospectively compare the measurements of the location and size of the inferior alveolar canal at the mental foramen and the length of the anterior loop between two cohorts of Americans and Taiwanese using cone-beam computed tomography (CBCT). METHODS: CBCT was performed with an I-CAT((r)) Cone Beam 3D Dental Imaging System and reconstructed into multiple-plane views to measure two populations. RESULTS: There was no statistically significant difference (P = 0.2681) in the distance from the mental foramen to the inferior border of the mandible (mandibular border height) between Americans (9.84 +/- 2.01 mm) and Taiwanese (10.13 +/- 1.66 mm). No significant difference was found (p = 0.1161) in the inferior alveolar canal diameter between these two cohorts (2.26 +/- 0.67 and 2.13 +/- 0.47 mm, respectively). However, the anterior loop length of Taiwanese (7.61 +/- 1.81 mm) was significantly longer than that of Americans (6.22 +/- 1.68 mm) (P < 0.0001). CONCLUSION: Our study indicated that (1) the location of mental foramen of Americans was closer to the inferior border of the mandible than Taiwanese; (2) the diameter of the inferior alveolar canal of Americans was larger than Taiwanese; (3) the anterior loop of Taiwanese was longer than Americans. These differences may be, at least partly, due to the racial influence and this information may possess potential valuable clinical relevance. PMID- 22669485 TI - Overexpression of Smad proteins, especially Smad7, in oral epithelial dysplasias. AB - OBJECTIVE: Transforming growth factor beta, via membrane-bound receptors and downstream Smad2-4, 7, can modulate tumorigenesis. Smad2 and Smad3 heterodimerize with Smad4, and the complex migrates to the nucleus to regulate the expression of target genes. Smad7 is a key negative regulator of this signaling pathway. This study aimed to examine Smad2-4, 7 expression and phosphorylated Smad2-3 (p-Smad2 3) in oral epithelial dysplasia and compared it with normal oral mucosa, hyperkeratosis/epithelial hyperplasia and squamous cell carcinoma (SCC). MATERIALS AND METHODS: Immunohistochemical staining of Smad2-4, 7 and p-Smad2-3, was performed for 75 samples of human oral mucosa, including hyperkeratosis/epithelial hyperplasia (n = 20), mild epithelial dysplasia (n = 11), moderate to severe epithelial dysplasia (n = 11), and SCC (n = 43). Normal buccal mucosa samples (n = 9) were also included. RESULTS: A significant increase in Smad7 expression was observed in the ascending order of samples of normal oral mucosa, hyperkeratosis/epithelial hyperplasia/mild oral epithelial dysplasia, moderate to severe oral epithelial dysplasia, and well-differentiated oral SCC/moderately to poorly differentiated oral SCC. Additionally, significant increases in Smad7 expression were noted as compared with expression of Smad2-4 and p-Smad2-3 in lesions of hyperkeratosis/epithelial hyperplasia, mild oral epithelial dysplasia, moderate to severe oral epithelial dysplasia, well differentiated oral SCC, and moderately to poorly differentiated oral SCC. CONCLUSIONS: Our results indicate that Smad proteins, particularly Smad7, in oral epithelial dysplasia and SCC could contribute to the attenuation of Smads anti proliferative signaling in cancer development. CLINICAL RELEVANCE: Smad7 could be a marker for risk of malignant transformation of oral epithelial dysplasia. PMID- 22669487 TI - Short-chain fatty acids suppress lipopolysaccharide-induced production of nitric oxide and proinflammatory cytokines through inhibition of NF-kappaB pathway in RAW264.7 cells. AB - Short-chain fatty acids (SCFAs) produced by the colonic bacterial fermentation of dietary fiber contribute a significant proportion of daily energy requirement. Furthermore, these compounds are modulators of macrophage function and potential targets for the development of new drugs. The aims of this study were to evaluate the effects of three types of SCFAs (sodium acetate (NaAc), sodium propionate (NaP), and sodium butyrate (NaB)) on the production of NO and inducible nitric oxide synthase (iNOS) and proinflammatory and antiinflammatory cytokines (tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL-1, IL-6, and IL-10)) and to observe the effect of NaAc on inhibiting lipopolysaccharide (LPS)-induced NF kappaB activation in LPS-stimulated RAW264.7 cells. The results show that three types of SCFAs (acetate, propionate, and butyrate) reduced the production of proinflammatory factors, including TNF-alpha, IL-1beta, IL-6, and NO, and inhibited the vitality of iNOS. Meanwhile, SCFAs enhanced the production of antiinflammatory cytokine IL-10 in lower concentrations (1-1,200 MUmol/L). Like NaB, NaAC inhibited LPS-induced NF-kappaB activation. These results may hold promise on the role that SCFAs have on the prevention and treatment of various inflammatory conditions. PMID- 22669488 TI - Effect of feed flushing during summer season on growth, reproductive performance and blood metabolites in Malpura ewes under semiarid tropical environment. AB - Feed scarcity during hot summer months is one of the major predisposing factors for low reproductive efficiency of livestock reared in hot semiarid environment. A study was conducted to assess the effect of concentrate supplementation during summer months on growth, reproductive performance, and blood metabolites in Malpura ewes. Twenty adult Malpura ewes were used in the present study. The ewes were divided into two groups viz, group 1 (n = 10; control) and group 2 (n = 10; concentrate supplementation). The study was conducted for a period of 35 days covering two estrus cycles. In the first cycle, only PGF(2alpha) was given to all ewes, while in second cycle, all ewes were synchronized for estrus using progesterone-impregnated intravaginal sponges and pregnant mare serum gonadotropin. The animals were allowed for grazing for 8-10 h per day. Apart from grazing, group 2 ewes were supplemented with concentrate mixture at 1.5 % of body weight. Concentrate supplementation had significant influence on body weight, ADG, estrus percentage, estrus duration, onset of estrus, ovulation response, plasma glucose, total protein, and urea. The present study reveals that ewes supplemented with concentrate mixture at 1.5 % of body weights during summer season significantly influenced the growth and reproductive performance of Malpura ewes. Further, the study signifies the importance of providing additional feed supplementation to ewes kept grazing under the conditions of a hot, semiarid environment to improve their reproductive efficiency. PMID- 22669486 TI - Osteoblast proliferation and differentiation on a barrier membrane in combination with BMP2 and TGFbeta1. AB - OBJECTIVES: Bioresorbable collagen membranes are routinely utilized in guided bone regeneration to selectively direct the growth and repopulation of bone cells in areas of insufficient volume. However, the exact nature by which alveolar osteoblasts react to barrier membranes as well as the effects following the addition of growth factors to the membranes are still poorly understood. The objective of the present study was therefore to investigate the effect of a bioresorbable collagen membrane soak-loaded in growth factors bone morphogenetic protein 2 (BMP2) or transforming growth factor beta1 (TGFbeta1) on osteoblast adhesion, proliferation, and differentiation. MATERIAL AND METHODS: Prior to experimental seeding, membranes were soaked in either BMP2 or TGFbeta1 at a concentration of 10 ng/ml for 5 min. RESULTS: Human osteoblasts adhered to all soak-loaded membranes as assessed by scanning electron microscopy. Growth factors BMP2 and TGFbeta1 increased osteoblast proliferation at 3 or 5 days post-seeding when compared to control collagen membranes. Analysis of real-time PCR revealed that administration of BMP2 increased osteoblast differentiation markers such as osterix, collagen I, and osteocalcin. BMP2 also increased mineralization of primary osteoblasts as demonstrated by alizarin red staining when compared to control and TGFbeta1 soak-loaded membranes. CONCLUSION: The combination of a collagen barrier membrane with growth factors TGFbeta1 and BMP2 significantly influenced adhesion, proliferation, and differentiation of primary human osteoblasts. CLINICAL RELEVANCE: The described in vitro effects following the combination of collagen barrier membranes with growth factors TGFbeta1 and BMP2 provide further biologic support for the clinical application of this treatment strategy in guided bone regeneration procedures. PMID- 22669489 TI - Layered inorganic-organic frameworks based on the 2,2-dimethylsuccinate ligand: structural diversity and its effect on nanosheet exfoliation and magnetic properties. AB - The structures of four new 2,2-dimethylsuccinate frameworks suitable for exfoliation into nanosheets using ultrasonication are reported. These hybrid compounds contain either monovalent (Li(+)) or divalent (Co(2+) and Zn(2+)) cations, and they all feature hydrophobically capped covalently bonded layers that only interact with each other via weak van der Waals forces. Critically this shows that the use of this dicarboxylate ligand generally yields two dimensional compounds suitable for simple and affordable nanosheet exfoliation. This extends the range of frameworks that can be exfoliated and highlights the 2,2 dimethylsuccinate ligand as an excellent versatile platform for the production of nanosheets. The topologies of the layers in each framework were found to vary significantly and this appears to have a significant effect on the relative size of the nanosheets produced; increased space between methyl groups and more extensive inorganic connectivity appears to favour the formation of thin nanosheets with larger lateral dimensions. Additionally the magnetic properties of two of these frameworks were examined, and it was found that both exhibit strong low dimensional antiferromagnetic coupling despite their well-separated layers preventing three dimensional magnetic order. PMID- 22669490 TI - [Diuretic resistance and mechanical ventilation in decompensated cor pulmonale: successful treatment by slow continuous ultrafiltration]. AB - We report on a 53-year-old male patient who presented with severe dyspnea at rest and massive volume overload because of decompensated cor pulmonale. Furthermore he suffered from stage 3 chronic kidney disease. As there was diuretics resistance and carbon dioxide narcosis, he had to be intubated and ventilated. The massive volume overload could be successfully treated with slow continuous ultrafiltration (SCUF) with removal of a volume of 27.5 l within 3 days. The SCUF therapy is an effective and gentle method to treat even an excessive volume overload based on diuretics resistance. PMID- 22669491 TI - [Oral factor Xa inhibitors or warfarin for stroke prophylaxis. ROCKET AF and ARISTOTLE studies]. PMID- 22669493 TI - Effects of statins on serum polyunsaturated fatty acids. PMID- 22669494 TI - Issues of banking breast cancer cells to generate mammospheres. AB - Identification of breast cancer stem cells, within the context of the tumor tissue, requires an efficient and standardized method to preserve the functional features of living cells. Although isolating cancer stem cells can be laborious and time-consuming, minimal processing may be advantageous for the banking of specimens from which cultures are not immediately needed. Homogenization of banking procedures will result in a reliable network of biorepositories for cooperative studies and several research groups are focusing on the issues of tissue banks for translational medicine. Most tissue banks collect and freeze unprocessed cancer specimens, which cannot therefore be used to generate viable cells. We discuss the principal issues of biobanking breast cancer living cells and protocols for mammospheres formation from single cell suspension of tumor cells. PMID- 22669492 TI - Philadelphia-positive acute lymphoblastic leukemia: current treatment options. AB - The Philadelphia chromosome (Ph), t(9;22), is seen in about 20 % to 30 % of adults diagnosed with acute lymphoblastic leukemia (ALL). It has been associated with poorer prognosis compared with Ph-negative ALL. Tyrosine kinase inhibitors (TKIs) targeting the BCR-ABL oncogenic protein from this translocation have been incorporated into treatment regimens used to treat patients with Ph-positive ALL. Imatinib has been the most widely used TKI with several published trials showing it produced better outcomes when combined with chemotherapy. Dasatinib, a more potent inhibitor than imatinib, has also been evaluated with promising results. However, relapses still occur at a high rate, and allogeneic stem cell transplant is considered, so far, a better curative option in first remission. Additional strategies have also included incorporation of TKIs in the post-transplant setting and the use of newer third generation TKIs. This review provides an update on emerging therapies for adults with Ph-positive ALL. PMID- 22669496 TI - Concussion in athletics: ongoing clinical and brain imaging research controversies. AB - Concussion, the most common form of traumatic brain injury, proves to be increasingly complex and not mild in nature as its synonymous term mild traumatic brain injury (mTBI) would imply. Despite the increasing occurrence and prevalence of mTBI there is no universally accepted definition and conventional brain imaging techniques lack the sensitivity to detect subtle changes it causes. Moreover, clinical management of sports induced mild traumatic brain injury has not changed much over the past decade. Advances in neuroimaging that include electroencephalography (EEG), functional magnetic resonance imaging (fMRI), resting-state functional connectivity, diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS) offer promise in aiding research into understanding the complexities and nuances of mTBI which may ultimately influence clinical management of the condition. In this paper the authors review the major findings from these advanced neuroimaging methods along with current controversy within this field of research. As mTBI is frequently associated with youth and sports injury this review focuses on sports-related mTBI in the younger population. PMID- 22669495 TI - Long-term proline exposure alters nucleotide catabolism and ectonucleotidase gene expression in zebrafish brain. AB - Hyperprolinemia is an inherited disorder of proline metabolism and hyperprolinemic patients can present neurological manifestations, such as seizures cognitive dysfunctions, and psychotic disorders. However, the underlying mechanisms of these symptoms are still unclear. Since adenine nucleotides play crucial roles in neurotransmission and neuromodulation, we evaluated the in vivo and in vitro effects of proline on ectonucleotidase activities and gene expression in zebrafish brain. For the in vivo studies, animals were exposed at two proline concentrations (1.5 and 3.0 mM) during 1 h or 7 days (short- or long term treatments, respectively). For the in vitro assays, different proline concentrations (ranging from 3.0 to 1000 MUM) were tested. Short-term proline exposure did not promote significant changes on the ectonucleotidase activities and gene expression. Long-term proline exposure significantly increased ATP catabolism in both concentrations tested (14 % and 22 %, respectively), whereas ADP and AMP hydrolysis were increased only at 3.0 mM proline (21 % and 17 %, respectively) when compared to control. Moreover, the relative gene expression of enpd3 increased in both treated groups after long-term proline, whereas enptd1 increased only at 3.0 mM proline. Proline in vitro did not promote significant changes on ectonucleotidase activities. Altogether, these data indicate that the enzymes responsible for the control of extracellular nucleotides levels might be altered after proline exposure in zebrafish, contributing to better understand the pathophysiology of this disease. Moreover, such findings might facilitate the use of the zebrafish as a complementary vertebrate model for studying inborn errors of amino acid metabolism. PMID- 22669497 TI - Genetic influences of resting state fMRI activity in language-related brain regions in healthy controls and schizophrenia patients: a pilot study. AB - Individuals with schizophrenia show a broad range of language impairments, similar to those observed in reading disability (RD). Genetic linkage and association studies of RD have identified a number of candidate RD-genes that are associated with neuronal migration. Some individuals with schizophrenia also show evidence of impaired cortical neuronal migration. We have previously linked RD related genes with gray matter distributions in healthy controls and schizophrenia. The aim of the current study was to extend these structural findings and to examine links between putative RD-genes and functional connectivity of language-related regions in healthy controls (n = 27) and schizophrenia (n = 28). Parallel independent component analysis (parallel-ICA) was used to examine the relationship between language-related regions extracted from resting-state fMRI and 16 single nucleotide polymorphisms (SNPs) spanning 5 RD-related genes. Parallel-ICA identified four significant fMRI-SNP relationships. A Left Broca-Superior/Inferior Parietal network was related to two KIAA0319 SNPs in controls but not in schizophrenia. For both diagnostic groups, a Broca-Medial Parietal network was related to two DCDC2 SNPs, while a Left Wernicke-Fronto-Occipital network was related to two KIAA0319 SNPs. A Bilateral Wernicke-Fronto-Parietal network was related to one KIAA0319 SNP only in controls. Thus, RD-genes influence functional connectivity in language-related regions, but no RD-gene uniquely affected network function in schizophrenia as compared to controls. This is in contrast with our previous study where RD-genes affected gray matter distribution in some structural networks in schizophrenia but not in controls. Thus these RD-genes may exert a more important influence on structure rather than function of language-related networks in schizophrenia. PMID- 22669498 TI - Population variability of phthalate metabolites and bisphenol A concentrations in spot urine samples versus 24- or 48-h collections. AB - Human exposure to phthalates and bisphenol A (BPA) can be assessed through urinary biomonitoring, but methods to infer daily intakes assume that spot sample concentrations are comparable to daily average concentrations. We evaluate this assumption using human biomonitoring data from Germany and the United States (US). The German data comprised three regional studies with spot samples and one with full-day samples analyzed for phthalate metabolites. The US data included: a study on DEHP metabolites and BPA involving eight persons supplying all urine voids (from which 24-h samples were constructed) for seven consecutive days; NHANES spot sample data on DEHP metabolites and BPA; and a regional study of children with 48-h samples analyzed for BPA. In the German data, measures of central tendency differed, but spot and 24-h samples showed generally comparable variance including 95th percentiles and maxima equidistant from central tendency measures. In contrast, the US adult data from the eight-person study showed similar central tendencies for phthalate metabolites and BPA, but generally greater variability for the spot samples, including higher 95th percentiles and maxima. When comparing children's BPA concentrations in NHANES spot and 48-h samples, distributions showed similar central tendency and variability. Overall, spot urinary concentrations of DEHP metabolites and BPA have variability roughly comparable with corresponding 24-h average concentrations obtained from a comparable population, suggesting that spot samples can be used to characterize population distributions of intakes. However, the analysis also suggests that caution should be exercised when interpreting the high end of spot sample data sets. PMID- 22669499 TI - Time series analysis of personal exposure to ambient air pollution and mortality using an exposure simulator. AB - This paper describes a modeling framework for estimating the acute effects of personal exposure to ambient air pollution in a time series design. First, a spatial hierarchical model is used to relate Census tract-level daily ambient concentrations and simulated exposures for a subset of the study period. The complete exposure time series is then imputed for risk estimation. Modeling exposure via a statistical model reduces the computational burden associated with simulating personal exposures considerably. This allows us to consider personal exposures at a finer spatial resolution to improve exposure assessment and for a longer study period. The proposed approach is applied to an analysis of fine particulate matter of <2.5 MUm in aerodynamic diameter (PM(2.5)) and daily mortality in the New York City metropolitan area during the period 2001-2005. Personal PM(2.5) exposures were simulated from the Stochastic Human Exposure and Dose Simulation. Accounting for exposure uncertainty, the authors estimated a 2.32% (95% posterior interval: 0.68, 3.94) increase in mortality per a 10 MUg/m(3) increase in personal exposure to PM(2.5) from outdoor sources on the previous day. The corresponding estimates per a 10 MUg/m(3) increase in PM(2.5) ambient concentration was 1.13% (95% confidence interval: 0.27, 2.00). The risks of mortality associated with PM(2.5) were also higher during the summer months. PMID- 22669500 TI - Personal exposure to volatile organic compounds in the Czech Republic. AB - Personal exposures to volatile organic compounds (VOCs) were measured in the three industrial cities in the Czech Republic, Ostrava, Karvina and Havirov, while the city of Prague served as a control in a large-scale molecular epidemiological study identifying the impacts of air pollution on human health. Office workers from Ostrava and city policemen from Karvina, Havirov and Prague were monitored in the winter and summer of 2009. Only adult non-smokers participated in the study (N=160). Radiello-diffusive passive samplers were used to measure the exposure to benzene, toluene, ethylbenzene, meta- plus para-xylene and ortho-xylene (BTEX). All participants completed a personal questionnaire and a time-location-activity diary (TLAD). The average personal BTEX exposure levels in both seasons were 7.2/34.3/4.4/16.1 MUg/m(3), respectively. The benzene levels were highest in winter in Karvina, Ostrava and Prague: 8.5, 7.2 and 5.3 MUg/m(3), respectively. The personal exposures to BTEX were higher than the corresponding stationary monitoring levels detected in the individual localities (P<0.001; except m,p-xylene in summer). The indoor environment, ETS (environmental tobacco smoke), cooking, a home-heating fireplace or gas stove, automobile use and being in a restaurant were important predictors for benzene personal exposure. Ostrava's outdoor benzene pollution was a significant factor increasing the exposure of the Ostrava study participants in winter (P<0.05). PMID- 22669501 TI - Mathematical simulation of membrane protein clustering for efficient signal transduction. AB - Initiation and propagation of cell signaling depend on productive interactions among signaling proteins at the plasma membrane. These diffusion-limited interactions can be influenced by features of the membrane that introduce barriers, such as cytoskeletal corrals, or microdomains that transiently confine both transmembrane receptors and membrane-tethered peripheral proteins. Membrane topographical features can lead to clustering of receptors and other membrane components, even under very dynamic conditions. This review considers the experimental and mathematical evidence that protein clustering impacts cell signaling in complex ways. Simulation approaches used to consider these stochastic processes are discussed. PMID- 22669502 TI - Optimal flow and pressure management in machine perfusion systems for organ preservation. AB - Intra-organ flow is the most critical parameter in machine-perfused organ preservation systems (MPS). Ultrasonic flow sensors (UFS) are commonly employed in MPS. However, UFS are sensitive to changes in fluid composition and temperature and require recalibration. Novel Coriolis-type mass flow sensors (CFS) may be more suitable for MPS because the measurement technique is not amenable to these factors. The effect of viscosity, colloids, temperature, pressure, and preservation solution on flow measurement accuracy of UFS and CFS was therefore investigated. A CFS-based MPS was built and validated for setpoint stability using porcine kidneys and the ability to reproduce different pressure and flow waveforms. The UFS exhibited a temperature- and preservation solution dependent overestimation of flow rate compared to the CFS. The CFS deviated minimally from the actual flow rate and did not require recalibration. The CFS based MPS conformed to the preprogrammed temperature, flow, pressure, and vascular resistance settings during 6-h kidney preservation. The system was also able to accurately reproduce different pressure and flow waveforms. Conclusively, CFS-based MPS are more suitable for organ preservation than UFS-based MPS. Our CFS-based MPS provides a versatile yet robust experimental platform for testing and validating different types of clinical and experimental MPS. PMID- 22669504 TI - Timing of traumatic brain injury in childhood and intellectual outcome. AB - OBJECTIVE: Typically, studies on outcomes after traumatic brain injury (TBI) have investigated whether a younger age at injury is associated with poorer recovery by comparing 2 age groups rather than participants injured across childhood. This study extended previous research by examining whether the influence of age on recovery fits an early vulnerability or critical developmental periods model. METHODS: Children with a TBI (n = 181) were categorized into 4 age-at-injury groups-infant, preschool, middle childhood, and late childhood--and were evaluated at least 2-years post-TBI on IQ. RESULTS: Overall, the middle childhood group had lower IQ scores across all domains. Infant and preschool groups performed below the late childhood group on nonverbal and processing speed domains. CONCLUSIONS: Contrary to expectations, children injured in middle childhood demonstrated the poorest outcomes; this age potentially coincides with a critical period of brain and cognitive development. PMID- 22669503 TI - Nutrient transport in human annulus fibrosus is affected by compressive strain and anisotropy. AB - The avascular intervertebral disc (IVD) receives nutrition via transport from surrounding vasculature; poor nutrition is believed to be a main cause of disc degeneration. In this study, we investigated the effects of mechanical deformation and anisotropy on the transport of two important nutrients--oxygen and glucose--in human annulus fibrosus (AF). The diffusivities of oxygen and glucose were measured under three levels of uniaxial confined compression--0, 10, and 20%--and in three directions--axial, circumferential, and radial. The glucose partition coefficient was also measured at three compression levels. Results for glucose and oxygen diffusivity in AF ranged from 4.46 * 10(-7) to 9.77 * 10(-6) cm(2)/s and were comparable to previous studies; the glucose partition coefficient ranged from 0.71 to 0.82 and was also similar to previous results. Transport properties were found to decrease with increasing deformation, likely caused by fluid exudation during tissue compression and reduction in pore size. Furthermore, diffusivity in the radial direction was lower than in the axial or circumferential directions, indicating that nutrient transport in human AF is anisotropic. This behavior is likely a consequence of the layered structure and unique collagen architecture of AF tissue. These findings are important for better understanding nutritional supply in IVD and related disc degeneration. PMID- 22669505 TI - Ochrobactrum anthropi: a rare cause of pneumonia. AB - Ochrobactrum anthropi, a Gram-negative bacillus, is an unusual human pathogen. It has been implicated primarily in catheter-related bloodstream infections. Sporadic cases of infection at other body sites have been reported. Pneumonia, however, is an exceedingly rare clinical manifestation; only one case has been reported in the medical literature so far. We present another case of lower respiratory tract infection secondary to O. anthropi in a patient who was critically ill, but recovered with a favorable outcome. We have provided an overview of clinical manifestations, diagnosis, and treatment of infections due to this rare microorganism. PMID- 22669506 TI - Flow cytometric quantification and immunophenotyping of leukemic stem cells in acute myeloid leukemia. AB - Leukemic stem cells (LSCs) are root of clonal growth in acute myeloid leukemia (AML) and responsible for the propagation of leukemic blasts (LBs). LSCs are considered as CD34 + CD38- population among LBs and often express as CD123, CD44, or CD184, which are rarely expressed on normal hematopoietic stem cells and could be the potential therapeutic targets. Using multi-color flow cytometry, we analyzed the proportions of CD34 + CD38- LSCs and expression of CD123, CD44, and CD184 on LSCs in 63 patients with AML. The median proportion of LSCs was 1.3 % (0.0-33.1 %) at the time of diagnosis. Of all patients, 74.6 % of them had CD123 positive LSCs, all patients had CD44-positive LSCs, and 85.7 % had CD184-positive LSCs, respectively. The proportions of LSCs were significantly lower in the complete remission (CR) group compared with non-CR group (P = 0.006). The lower proportions of LSCs in CR group indicated that measurement of the proportion of LSCs might be helpful to predict the prognosis of AML. PMID- 22669507 TI - Hexavalent chromate reduction by alkaliphilic Amphibacillus sp. KSUCr3 is mediated by copper-dependent membrane-associated Cr(VI) reductase. AB - The present study was aimed to localize and characterize hexavalent chromate [Cr(VI)] reductase activity of the extreme alkaliphilic Amphibacillus sp. KSUCr3 (optimal growth pH 10.5). The resting cells were able to reduce about 62 % of the toxic heavy metal Cr(VI) at initial concentration of 200 MUM within 30 min. Cell permeabilization resulted in decrease of Cr(VI) reduction in comparison to untreated cells. Enzymatic assays of different sub-cellular fractions of Amphibacillus sp. KSUCr3 demonstrated that the Cr(VI) reductase was mainly associated with the membranous fraction and expressed constitutively. In vitro studies of the crude enzyme indicated that copper ion was essential for Cr(VI) reductase activity. In addition, Ca2+ and Mn2+ slightly stimulated the chromate reductase activity. Glucose was the best external electron donor, showing enhancement of the enzyme activity by about 3.5-fold. The K (m) and V (max) determined for chromate reductase activity in the membranous fraction were 23.8 MUM Cr(VI) and 72 MUmol/min/mg of protein, respectively. Cr(VI) reductase activity was maximum at 40 degrees C and pH 7.0 and it was significantly inhibited in the presence of disulfide reducers (2-mercaptoethanol), ion chelating agent (EDTA), and respiratory inhibitors (CN and Azide). Complete reduction of 100 and 200 MUM of Cr(VI) by membrane associated enzyme were observed within 40 and 180 min, respectively. However, it should be noted that biochemical characterization has been done with crude enzyme only, and that final conclusion can only be drawn with the purified enzyme. PMID- 22669508 TI - Paraoxonase 1, atherosclerosis and arterial stiffness in renal patients. AB - Atherosclerosis is an important contributor to increased cardiovascular burden in populations with and without renal disease. Paraoxonases (PON) are a group of enzymes that hydrolyse organophosphates. Recent evidence indicates a protective role for PON in patients with coronary artery disease and atherosclerosis. Although data are limited, the low enzyme activity found in patients with chronic kidney disease and renal transplants has been linked to atherosclerosis and arterial stiffness. In this paper, we review the emerging role of PON1 in the pathophysiology of atherosclerosis and arterial stiffness in patients with chronic kidney disease. PMID- 22669509 TI - IL-6 and PACAP receptor expression and localization after global brain ischemia in mice. AB - Pituitary adenylate cyclase-activating polypeptide (PACAP) exerts a neuroprotective action against ischemic damage. This action is mediated by the interleukin-6 (IL-6) pathway. However, as the expression patterns of PACAP receptors and IL-6 following ischemia are not understood, we evaluated them in the mouse hippocampus in response to ischemia induced by bilateral common carotid artery occlusion. Real-time PCR determination of PAC1R mRNA expression in the hippocampus was significantly elevated on day 7 after ischemia. VPAC1R mRNA expression was significantly decreased 3 days after the ischemic episode, while VPAC2R mRNA expression showed a nonsignificant tendency to increase on day 7. IL 6 mRNA expression was significantly increased on day 3 and peaked on day 7 after ischemia. The mRNA expression of activity-dependent neuroprotective protein, which is a neuroprotective factor stimulated by PACAP, remained virtually unchanged in response to ischemia. IL-6 immunoreactivity was detected in the CA1 pyramidal cell layer and colocalized with the neuronal marker NeuN on day 1 after ischemia. On day 3, irregularly shaped IL-6-immunopositive cells colocalized with the astrocytic marker glial fibrillary acidic protein but not with the microglial marker Iba1. PAC1R immunoreactivity co-labeled with IL-6 immunoreactivity. These results suggest that PACAP could stimulate IL-6 secretion by neurons during the acute phase after an ischemic episode and thereafter by astrocytes during the subacute phase. PMID- 22669510 TI - Age at onset in LRRK2-associated PD is modified by SNCA variants. AB - Mutations in the leucine-rich repeat kinase 2 (LRRK2) and alpha-synuclein (SNCA) genes are known genetic causes of Parkinson's disease (PD). Recently, a genetic variant in SNCA has been associated with a lower age at onset in idiopathic PD (IPD). We genotyped the SNCA polymorphism rs356219 in 84 LRRK2-associated PD patients carrying the G2019S mutation. We found that a SNCA genetic variant is associated with an earlier age at onset in LRRK2-associated PD. Our results support the notion that SNCA variants can modify the pathogenic effect of LRRK2 mutations as described previously for IPD. PMID- 22669511 TI - Involvement of p38 MAPK-dependent activator protein (AP-1) activation in modulation of gastric mucosal inflammatory responses to Helicobacter pylori by ghrelin. AB - A peptide hormone, ghrelin, plays an important role in modulation of gastric mucosal inflammatory responses to Helicobacter pylori infection by controlling the cross-talk between nitric oxide synthase (NOS) and cyclooxygenase (COX) enzyme systems. In this study, we report that H. pylori LPS-elicited induction in gastric mucosal COX-2 and inducible (i) iNOS protein expression, and the impairment in constitutive (c) cNOS phosphorylation, was associated with mitogen activated protein kinase, c-Jun N-terminal kinase (JNK), extracellular signal regulated kinase and p38 activation, and occurred with the involvement of transcription factors, CCATT/enhancer-binding protein (C/EBP) delta, cAMP response element-binding protein, activator protein-1 (AP-1), and NF-kappaB. The modulatory effect of ghrelin on the LPS-induced changes was manifested in the inhibition of nuclear translocation of p65 NF-kappaB and C/EBPdelta, and suppression in AP-1 activation, and the inhibition in phosphorylation of JNK and p38, as well as their respective downstream targets, c-Jun and ATF-2. However, only the inhibition of p38-mediated ATF-2 phosphorylation was reflected in the reduced expression of COX-2 protein. Further, the effect of ghrelin of the LPS induced changes was reflected in the increase in Src/Akt-dependent cNOS activation through phosphorylation and the inhibition of cNOS-mediated IKK-beta S nitrosylation. Our findings indicate ghrelin counters the proinflammatory consequences of H. pylori by interfering with the p38/ATF-2-induced AP-1 activation in association with concurrent up-regulation in Src/Akt-dependent cNOS phosphorylation. PMID- 22669512 TI - Identification of RARRES1 as a core regulator in liver fibrosis. AB - Genetic factors contribute to progression and modulation of hepatic fibrosis. High throughput genomics/transcriptomics approaches aiming at identifying key regulators of fibrosis development are tainted with the difficulty of separating essential biological "driver" from modifier genes. We applied a comparative transcriptomics approach and investigated fibrosis development in different organs to identify overlapping expression changes, since these genes may be part of core pathways in fibrosis development. Gene expression was analysed on publicly available microarray data from liver, lung and kidney fibrosis. RARRES1, AGER and S100A2 were differentially regulated in all fibrosis experiments. RARRES1 was extensively analysed by means of advanced bioinformatics analyses and functional studies. Microarray and Western Blot analysis of a standard liver fibrosis model (CCl(4)) demonstrated an early induction of RARRES1 mRNA and protein expression. In addition, quantitative RT-PCR in tissue samples from patients with advanced liver fibrosis showed higher expression as compared to non fibrotic biopsies. Microarray analysis of RARRES1 overexpressing cells identified an enrichment of a major signature associated with fibrosis. Furthermore, RARRES1 expression increased during in vitro activation of hepatic stellate cells. To further verify the pro-fibrogenic role across organs, we demonstrated an increase in RARRES1 expression in a rat lung fibrosis model induced by adenoviral TGF beta1 induction. We have performed a comparative transcriptomics analysis in order to identify core pathways of liver fibrogenesis, confirmed a candidate gene and enlightened the up- and downstream mechanisms of its action leading to fibrosis across organs and species. PMID- 22669513 TI - Headaches associated with papilledema. AB - Headaches associated with papilledema may be both life-threatening as well as vision-threatening. This review will review the following clinical features: (1) the character of headaches associated with increased intracranial pressure; (2) the visual symptoms associated with papilledema; (3) the funduscopic findings of true papilledema versus pseudo-papilledema; (4) the role of ancillary ophthalmological testing such as visual fields and spectral domain optical coherence tomography; (5) the neuro-radiological evaluation of patients with headaches and papilledema; (6) the treatment of vision-threatening papilledema. PMID- 22669514 TI - 7-Nitro-4-(phenylthio)benzofurazan is a potent generator of superoxide and hydrogen peroxide. AB - Here, we report on 7-nitro-4-(phenylthio)benzofurazan (NBF-SPh), the most potent derivative among a set of patented anticancer 7-nitrobenzofurazans (NBFs), which have been suggested to function by perturbing protein-protein interactions. We demonstrate that NBF-SPh participates in toxic redox-cycling, rapidly generating reactive oxygen species (ROS) in the presence of molecular oxygen, and this is the first report to detail ROS production for any of the anticancer NBFs. Oxygraph studies showed that NBF-SPh consumes molecular oxygen at a substantial rate, rivaling even plumbagin, menadione, and juglone. Biochemical and enzymatic assays identified superoxide and hydrogen peroxide as products of its redox cycling activity, and the rapid rate of ROS production appears to be sufficient to account for some of the toxicity of NBF-SPh (LC(50) = 12.1 MUM), possibly explaining why tumor cells exhibit a sharp threshold for tolerating the compound. In cell cultures, lipid peroxidation was enhanced after treatment with NBF-SPh, as measured by 2-thiobarbituric acid-reactive substances, indicating a significant accumulation of ROS. Thioglycerol rescued cell death and increased survival by 15-fold to 20-fold, but pyruvate and uric acid were ineffective protectants. We also observed that the redox-cycling activity of NBF-SPh became exhausted after an average of approximately 19 cycles per NBF-SPh molecule. Electrochemical and computational analyses suggest that partial reduction of NBF SPh enhances electrophilicity, which appears to encourage scavenging activity and contribute to electrophilic toxicity. PMID- 22669516 TI - Endosomes and lysosomes are involved in early steps of Tl(III)-mediated apoptosis in rat pheochromocytoma (PC12) cells. AB - The mechanisms that mediate thallium (Tl) toxicity are still not completely understood. The exposure of rat pheochromocytoma (PC12) cells to Tl(I) or Tl(III) activates both mitochondrial (Tl(I) and Tl(III)) and extrinsic (Tl(III)) pathways of apoptosis. In this work we evaluated the hypothesis that the effects of Tl(III) may be mediated by the damage to lysosomes, where it might be incorporated following the route of iron uptake. PC12 cells exposed for 3 h to 100 MUM Tl(III) presented marked endosomal acidification, effect that was absent when cells were incubated in a serum-free medium and that was fully recovered when the latter was supplemented with transferrin. After 6 h of incubation the colocalization of cathepsins D and B with the lysosomal marker Lamp-1 was decreased together with an increase in the total activity of the enzymes. A permanent damage to lysosomes after 18 h of exposure was evidenced from the impairment of acridine orange uptake. Cathepsin D caused the cleavage of pro apoptotic protein BID that is involved in the activation of the intrinsic pathway of apoptosis. Supporting that, BID cleavage and the activation of caspase 3 by Tl(III) were fully prevented when cells were preincubated with cathepsin D inhibitor (pepstatin A) and only partially prevented when cathepsin B inhibitor (E64d) was used. None of these inhibitors affected BID cleavage or caspase 3 activation in Tl(I)-treated cells. Together, experimental results support the role of Tl(III) uptake by the acidic cell compartments and their involvement in the early steps of Tl(III)-mediated PC12 cells apoptosis. PMID- 22669515 TI - Interactions of silica nanoparticles with lung epithelial cells and the association to flotillins. AB - Amorphous silica nanoparticles (aSNPs) gain increasing popularity for industrial and therapeutic claims. The lung with its surface area of 100-140 m(2) displays an ideal target for therapeutic approaches, but it represents also a serious area of attack for harmful nanomaterials. The exact nature of the cytotoxic effects of NPs is still unknown. Furthermore, cellular pathways and the destiny of internalized NPs are still poorly understood. Therefore, we examined the cytotoxicity (MTS, LDH) and inflammatory responses (IL-8) for different-sized aSNPs (30, 70, 300 nm) on our lung epithelial cells line NCI H441 and endothelial cell line ISO-HAS-1. Additionally, colocalization studies have been conducted via immunofluorescence staining for flotillin-1- and flotillin-2-bearing endocytic vesicles. Subsequently, the relevance of flotillins concerning the viability of aSNP-exposed epithelial cells has been evaluated using flotillin-1/2 depleted cells (siRNA). This study reveals the relevance of the nanoparticle size regarding cytotoxicity (MTS, LDH) and inflammatory responses (IL-8), whereat the smaller the size of the nanoparticle is, the more harmful are the effects. All different aSNP sizes have been incorporated in flotillin-1- and flotillin-2 labelled vesicles in lung epithelial and endothelial cells, which display a marker for late endosomal or lysosomal structures and appear to exhibit a clathrin- or caveolae-independent mode of endocytosis. Flotillin-depleted H441 showed a clearly decreased uptake of aSNPs. Additionally, the viability of aSNP exposed cells was reduced in these cells. These findings indicate a contribution of flotillins in as yet unknown (clathrin or caveolae-independent) endocytosis mechanisms and (or) endosomal storage. PMID- 22669517 TI - Primary spinal epidural rhabdomyosarcoma: a case report and review of the literature. AB - BACKGROUND: Primary intraspinal sarcomas are very rare in children. Rhabdomyosarcoma (RMS) is a highly aggressive and rapidly growing sarcoma with skeletal origin that occasionally appears in the spinal epidural space. METHOD: We report a 13-year-old girl who presented with back pain, progressive paraparesis, and urinary retention. She had muscular weakness in her lower extremities and absent deep tendon reflex. An epidural dumbbell-shape mass at T11 T12 level was observed on MRI. The patient underwent T12 hemilaminectomy, partial T11 hemilaminectomy, and right facetectomy. A large, firm, dark-red vascular epidural tumor was found compressing the cord. The tumor which extended to intracanal and foraminal parts was removed completely. DISCUSSION: Histopathological examination revealed undifferentiated small round and oval tumoral cells. Immunohistochemical staining was positive for vimentin, desmin, and myogenin. The final diagnosis was alveolar RMS. She received radiotherapy and chemotherapy by vincristine, actinomycin-D, doxorubicin, and ifosfamide. The patient was in good condition with no tumor recurrence or metastasis at the 1 year follow-up. PMID- 22669519 TI - The most important decision in decompressive craniectomy in pediatric traumatic brain injury: when not to perform it! PMID- 22669518 TI - Pediatric meningiomas: a single-center experience with 15 consecutive cases and review of the literature. AB - OBJECTIVE: The goal of this study was to determine the epidemiology, clinical presentation, associated factors, pathological features, and treatment outcome of pediatric meningiomas in a single-center institution. METHODS: Clinical data of 15 patients under 18 years of age operated on for meningiomas from January 1994 to December 2010 were reviewed. RESULTS: The study group included nine males and six females (mean age of 13 years at surgery). The most common symptoms at presentation were headaches in 6 out of 15 (40 %), raised intracranial pressure in 3 out of 15 (20 %), and seizures in 3 out of 15 (20 %). Sole operated tumors were found in 12 out of 15 (80 %), whose location is as follows: parasagittal in 4 out of 12 (33.3 %), 2 in the convexity (16.6 %), 2 at the skull base (16.6 %), and 4 in other sites (33.3 %). Six children presented with radiation-induced (RT) meningiomas and five had evidence of neurofibromatosis type 2 (NF2). Three patients had multiple meningiomas (all of them had NF2). Simpson's grade I excision was achieved in 12 out of 15 (80 %). On histopathology, 11 out of 15 (73.3 %) were grade I and 4 out of 15 (26.6 %) were grade II (all of them atypical). Five tumors (33.3 %) recurred, four of which had RT or NF2. During the mean follow-up period of 5 years, 12 out of 15 (80 %) had a good outcome (GOS=5). CONCLUSIONS: Childhood meningiomas are uncommon lesions with a slight male predominance. Absence of large series with long follow-up precludes any definite conclusions on the clinical course and outcome of these tumors. Associated factors (such as RT and NF2), location, and extent of excision appear to be more important than histopathological grade in predicting outcome. PMID- 22669521 TI - The history of the surgical repair of spina bifida. AB - INTRODUCTION: The history of surgical spina bifida repair has seen many successes and failures. Many early surgeons attempted treatment of open spina bifida defects before a clear understanding of the disease process or pathology had been discovered. CONCLUSIONS: The attempts, while often fruitless, served to better our understanding of the disease and represent stepping-stones to the treatment we successfully use today. The present paper reviews the history of the surgical treatment of myelomeningoceles. PMID- 22669522 TI - Advanced comparative cytogenetic analysis of X chromosomes in river buffalo, cattle, sheep, and human. AB - Based on a recently generated comprehensive gene map for Ovis aries chromosome X (OARX) with an approximately even locus distribution, we assigned selected bacterial artificial chromosome (BAC) probes corresponding to these OARX loci to Bubalus bubalis (BBU) and Bos taurus (BTA) by comparative fluorescence in-situ hybridization (FISH) to improve cytogenetically the X chromosome maps in these species. Twenty-five added loci in BBUX and BTAX, respectively, contribute to a more detailed description of the cytogenetic organization of these chromosomes. Further seven loci were identified in OARX and two DNA probes were assigned to X and Y chromosomes in river buffalo, cattle, and sheep, respectively, and thus identified loci in the pseudoautosomal region. The additional assignments double the number of cytogenetic loci in BBUX and increase their number in BTAX and OARX. The larger quantity of cytogenetic anchors allows a more precise morphological comparison of bovid X chromosomes among each other and with the Homo sapiens (HSA) X chromosome. The anchor loci confirm and refine syntenic fragments in HSAX and identify several evolutionary breakpoints between the compared chromosomes. The cytogenetic assignments in BBUX, BTAX, and OARX represent useable anchors for the ongoing genome sequence assembly in Bovidae. PMID- 22669523 TI - Validity of the Beck Depression Inventory as a screening tool for a clinical mood disorder in bariatric surgery candidates. AB - BACKGROUND: The Beck Depression Inventory (BDI) is one of the most commonly used instruments to assess depression in persons with obesity. While it has been validated in normal and psychiatric populations, in obese populations, its validity remains uncertain. This study aimed to investigate the validity and reliability of the BDI-IA and BDI-II in severely obese bariatric surgery candidates. METHODS: Consecutive new candidates at a bariatric surgery clinic were invited to participate in the study by their consulting surgeon. All candidates were assessed using the Structured Clinical Interview for DSM-IV Disorders (SCID-I); 118 completed the BDI-IA and 83 completed the BDI-II. Two hundred one patients (response rate, 88 %) participated in the study. The current sample (82 % female) had an average body mass index of 42.83 +/- 6.34 and an average age of 45 +/- 12 years. RESULTS: Based on the SCID-I, 54 candidates (26.9 %) met the criteria for a mood disorder, with 37 meeting the criteria for current major depressive disorder. Individuals diagnosed with a clinical mood disorder had significantly higher scores on the BDI (BDI-IA, 23.59 +/- 9.69 vs. 12.76 +/- 8.29; BDI-II, 22.93 +/- 5.22 vs. 11.25 +/- 8.44). Our results indicated that, as a screening tool for a clinical mood disorder, the BDI-II had an optimal cutoff of 13, with a sensitivity of 100 and specificity of 67.75. CONCLUSIONS: Results indicated that the BDI-IA should not be used as a tool to measure depressive symptomatology in obese bariatric surgery candidates. No cutoff was identified with adequate sensitivity and specificity, and over 20 % of patients were misclassified. As a screening tool for a clinical mood disorder, the BDI-II was adequate; however, prevalence rates were significantly overestimated. PMID- 22669524 TI - Pulmonary extramedullary haematopoiesis. AB - A 72-year-old Caucasian lady with myeloproliferative disorder was admitted for evaluation of progressive dyspnoea, weight loss, fatigue and mild hypoxia. A diffuse ground glass opacity was seen on CT pulmonary angiogram. Differential diagnoses included heart failure, infection, progression of myeloproliferative disorder with extramedullary haematopoiesis, thromboembolism or hydroxyurea induced lung injury. Bronchoscopy and broncho-alveolar lavage were uninformative however lung biopsy with video-assisted thoracoscopy revealed extramedullary haematopoiesis within lung parenchyma. This is a very rare complication of myeloproliferative disorder and the authors discuss the significance of the case, review the literature and report the patient's progress. PMID- 22669525 TI - The development of focal segmental glomerulosclerosis secondary to anabolic steroid abuse. AB - The authors present the case of a patient who presented to the nephrology department of a district general hospital with end-stage renal failure. He presented with malignant hypertension and symptoms and signs of uraemia. He also gave a history of prior abuse of anabolic steroids over a number of years. Renal biopsy was performed and the findings were in keeping with a diagnosis of advanced focal segmental glomerulosclerosis (FSGS). The patient went on to require renal replacement therapy within weeks of presentation. The authors suggest that anabolic steroid abuse is a direct cause of FSGS. People with raised body mass index are known to be at increased risk of developing this condition, due to increased haemodynamic stress on the glomeruli, with subsequent development of sclerosis. However, the authors believe that anabolic steroid abuse may be an independent risk factor, and that anabolic steroids have a direct nephrotoxic effect that leads to a more advanced initial presentation with rapid decline in renal function. PMID- 22669526 TI - A report on a rare case of Klebsiella ozaenae causing atrophic rhinitis in the UK. AB - Ozena is a chronic disease of the nasal cavity characterised by atrophy of the mucosa and bone caused by Klebsiella ozaenae. It is endemic to subtropical and temperate regions affecting the lower socio-economic group, usually the poor who live in unhygienic conditions. It is a rare disease in the UK. There is usually a delay in diagnosis due to unfamiliarity of the disease. A 25-year-old Nigerian migrant presented with nasal obstruction with purulent nasal discharge. Isolation of the bacterium was found from cultures of nasal discharge, crusting and tissue biopsies. She was treated successfully with ciprofloxacin. It is important to consider this rare condition in cases of nasal obstruction even in non-endemic areas especially with the advances of modern travel. PMID- 22669527 TI - Gliadin allergy manifested with chronic urticaria, headache and amenorrhea. AB - Gluten intolerance is an autoimmune enteropathy caused by heterogeneous mixture of wheat storage proteins. Malabsorption symptoms imply diarrhoea, abdominal pain/bloating and weight loss. This case describes a 22-year-old female subject, who had chronic headache, joint pain, urticaria and long period of amenorrhea. Skin prick tests revealed a sensitisation to alpha-gliadin, while neurological, gynaecological, endocrine and clinical-laboratory examinations did not justify the above-mentioned symptoms. Gluten-free diet resolved chronic symptoms and re established the menstrual cycle, whereas a temporary gliadin daily diet re exacerbated all clinical symptoms. Urticaria occurred 20 min and the chronic headache the next day after exposure to the gliadin-rich diet. In addition, the missing of the expected menstrual bleeding was observed. This case demonstrates that gliadin intake can induce malabsorption and 'idiopathic' neuronal or gynaecological symptoms. PMID- 22669528 TI - Ocular and orbital metastases presenting as a first sign of gastric adenocarcinoma. AB - The authors report a case of simultaneous choroidal and orbital metastases with optic nerve involvement presenting as an initial manifestation of gastric adenocarcinoma. To our knowledge, this is the first case of its kind reported in the literature where a 60 years male presented with 6 months history of progressive painful diminution of vision in his left eye associated with inward and upward rotation of the same globe. Examination of left eye revealed displacement of the globe superomedially by an inferolateral mass with restriction of ocular motility in levoversion. Fundus examination showed exudative retinal detachment with a subretinal mass which was supported by the ocular ultrasonography. Intraocular and orbital tumour was demonstrated by CT. Endoscopic biopsy revealed adenocarcinoma of the stomach. The left orbit was exenterated and specimen was sent for histopathological examination which confirmed the presence of same metastatic tumour cells in the eye and orbit. The patient underwent chemotherapy and radiotherapy for gastric carcinoma but the patient died after 6 months. PMID- 22669529 TI - Systemic vasculitis: a dual diagnosis? AB - The authors describe a 25-year-old male with systemic vasculitis fulfilling the American College of Rheumatology classification criteria for both granulomatosis with polyangiitis (Wegener's granulomatosis) and polyarteritis nodosa. The patient was diagnosed with granulomatosis with polyangiitis following a mediastinal biopsy which revealed necrotising granulomas of the large airways, a positive cytoplasmic antineutrophil cytoplasmic antibodies and high antiproteinase 3 antibody titre. He then developed acute right-sided abdominal and testicular pain as well as areas of hyperaesthesia and parasthesiae on both lower limbs. He was found to have focal crescentic glomerulonephritis and mononeuritis multiplex, in keeping with his diagnosis of granulomatosis with polyangiitis, as well as two areas of infarction in his right testicle and multiple aneurysms of his hepatic and right renal arteries, more typical of polyarteritis nodosa. His symptoms developed 6 weeks after hepatitis B vaccination, which may have played an aetiological role. PMID- 22669530 TI - The middle ear mass: a rare but important diagnosis. AB - The authors report a rare case of primary intracranial meningioma presenting as a middle ear mass with conductive hearing loss. The authors aim to highlight the importance of diagnosing a middle ear mass, which although rare, may have a substantial impact on ongoing patient management. A discussion of other middle ear pathologies is made in order to demonstrate the subtle differences in presentation. PMID- 22669531 TI - Ulcerative skin lesions in a child with colitis ulcerosa after colectomy. PMID- 22669532 TI - In silico evaluation of TERT inhibition by anticancer drugs. AB - The activation of telomerase represents an early step in carcinogenesis. Increased telomerase expression in malignant tumors suggests that telomerase inactivation may represent a potential chemotherapeutic target. In this work, existing anticancer drugs were docked against telomerase reverse transcriptase (TERT) using a Lamarckian genetic algorithm (LGA). Autodock's scoring function was applied to each of the molecules in order to identify the inhibitor with the strongest pharmacological action. The structural insights provided by this study regarding binding poses and possible interactions, free energies of binding, and drug scores aided in the identification of potential inhibitory compounds. The ranks of the various ligands investigated were based on the final docked energy values. Among nine selected compounds, vindesine, temsirolimus, and cyclosporine were found to be more potent TERT inhibitors than the standard inhibitor, curcumin. PMID- 22669533 TI - Theoretical description of halogen bonding - an insight based on the natural orbitals for chemical valence combined with the extended-transition-state method (ETS-NOCV). AB - In the present study we have characterized the halogen bonding in selected molecules H3N-ICF3 (1-NH 3 ), (PH3)2C-ICF3 (1-CPH 3 ), C3H7Br-(IN2H2C3)2C6H4 (2 Br), H2-(IN2H2C3)2C6H4 (2-H 2 ) and Cl-(IC6F5)2C7H10N2O5 (3-Cl), containing from one halogen bond (1-NH 3 , 1-CPH 3 ) up to four connections in 3-Cl (the two Cl HN and two Cl-I), based on recently proposed ETS-NOCV analysis. It was found based on the NOCV-deformation density components that the halogen bonding C-X (...) B (X-halogen atom, B-Lewis base), contains a large degree of covalent contribution (the charge transfer to X (...) B inter-atomic region) supported further by the electron donation from base atom B to the empty sigma*(C-X) orbital. Such charge transfers can be of similar importance compared to the electrostatic stabilization. Further, the covalent part of halogen bonding is due to the presence of sigma-hole at outer part of halogen atom (X). ETS-NOCV approach allowed to visualize formation of the sigma-hole at iodine atom of CF3I molecule. It has also been demonstrated that strongly electrophilic halogen bond donor, [C6H4(C3H2N2I)2][OTf]2, can activate chemically inert isopropyl bromide (2 Br) moiety via formation of Br-I bonding and bind the hydrogen molecule (2-H 2 ). Finally, ETS-NOCV analysis performed for 3-Cl leads to the conclusion that, in terms of the orbital-interaction component, the strength of halogen (Cl-I) bond is roughly three times more important than the hydrogen bonding (Cl-HN). PMID- 22669534 TI - Usnic acid inhibits breast tumor angiogenesis and growth by suppressing VEGFR2 mediated AKT and ERK1/2 signaling pathways. AB - Tumor growth depends on angiogenesis and inducing angiogenesis is one of the most important hallmarks in the cancer development. Treatment with small molecules that inhibit angiogenesis has been an effective strategy for anti-cancer therapy. Some anti-angiogenic factors are derived from traditional Chinese herbs. Usnic acid (UA), an active compound mainly found in lichens, has shown some biological and physiological activities. However, the role and mechanism of UA in tumor angiogenesis are still unknown. The aim of this study was to assess the effects of UA on tumor angiogenesis. In this study, we demonstrated that UA strongly inhibited in vivo angiogenesis in a chick embryo chorioallantoic membrane assay and vascular endothelial growth factor-induced mouse corneal angiogenesis model. In a mouse xenograft tumor model, UA suppressed Bcap-37 breast tumor growth and angiogenesis without affecting mice body weight. In an in vitro assay, UA not only significantly inhibited endothelial cell proliferation, migration and tube formation, but also induced morphological changes and apoptosis in endothelial cells. In addition, UA inhibited Bcap-37 tumor cell proliferation. Moreover, western blot analysis of cell signaling molecules indicated that UA blocked vascular endothelial growth factor receptor (VEGFR) 2 mediated Extracellular signal-regulated protein kinases 1 and 2(ERK1/2) and AKT/P70S6K signaling pathways in endothelial cells. These results provided the first evidence of the biological function and molecular mechanism of UA in tumor angiogenesis. PMID- 22669535 TI - Endothelial dysfunction as an underlying pathophysiological condition of chronic kidney disease. AB - Renal dysfunction and cardiovascular disorders affect each other adversely and worsen existing pathophysiological conditions. These disorders are extremely diverse in terms of pathology. Vascular disorders, in particular vascular endothelial dysfunction, are common risk factors for each other. Early endothelial dysfunction reduces vascular relaxation and causes inflammatory cell infiltration and slight inflammation in blood vessels. Endothelial dysfunction in the kidneys manifests as albuminuria. Proactive treatment is required in the early phase of endothelial dysfunction to prevent cardiovascular disease in chronic kidney disease patients. PMID- 22669536 TI - A Ypt/Rab GTPase module makes a PAS. AB - Organization of membrane micro-domains by Ypt/Rab GTPases is key for all membrane trafficking events in eukaryotic cells. Since autophagy is a membrane trafficking process, it was expected that these GTPases would play a role in autophagy as well. While evidence about participation of Ypt/Rabs in autophagy is beginning to emerge, the mechanisms by which they act in this process are still not clear. Moreover, it is still questionable if and how Ypt/Rabs coordinate autophagy with other cellular trafficking processes. Yeast Ypt1 and its mammalian homolog Rab1 are required for both endoplasmic reticulum (ER)-to-Golgi transport and autophagy, suggesting that they coordinate these two processes. In our recent paper, we identify Atg11, a bona fide phagophore assembly site (PAS) component, as a downstream effector of Ypt1. Moreover, we show that three components of a GTPase module--the Ypt1 activator, Trs85-containing TRAPP complex, Ypt1, and the Atg11 effector--interact on the PAS and are required for PAS formation during selective autophagy. We propose that Ypt/Rabs coordinate the secretory and the autophagic pathways by recruiting process-specific effectors. PMID- 22669537 TI - [Addiction counselling in the surgical emergency room. Implementation of a brief intervention for alcohol-intoxicated patients]. AB - INTRODUCTION: The primary care system, especially emergency rooms, seems to be an ideal location for the implementation of brief interventions for secondary prevention of alcohol use disorders. The present study examines whether a brief intervention can both lead to a reduction in alcohol quantity and consumption frequency as well as to an increased contact with alcohol counselling services. METHODS: The brief intervention for patients with alcohol consumption consisted of an interview about the alcohol drinking patterns and the delivery of a flyer from the local counselling services. One month later a follow-up interview was conducted. RESULTS: A total of 64 patients participated in the study; 37 patients gave their consent for follow-up. Patients with harmful/dependent alcohol use significantly reduced their alcohol amount (p<0,001) and consumption frequency (p<0,02). Patients who linked the injury to the consumed alcohol reduced their drinking frequency significantly more than those who did not (p=0,01). The intervention had no influence on the contact rate with counselling services. DISCUSSION: Promising evidence was found, which needs confirmation in the form of randomized controlled trials with focus on long-term effects. PMID- 22669538 TI - [Septic arthritis as an initial manifestation of a bacterial endocarditis]. AB - Septic arthritis due to endocarditis is a rare and life-threatening disease. Endocarditis occurs with an incidence of 30 patients per 1 million citizens/year. Staphylococcus aureus is one of the most common causative pathogens. Methicillin resistant Staphylococcus aureus (MRSA) can lead to a severe outcome with a high mortality rate, and embolic complications of the kidney, brain, and spleen are seen in one third of all cases. The diagnosis and treatment of endocarditis is a challenge for all health care providers. We report about a patient who was admitted to our hospital with generalized sepsis of unknown origin. PMID- 22669539 TI - Predictive value of morphological features in patients with autism versus normal controls. AB - We investigated the predictive power of morphological features in 224 autistic patients and 224 matched-pairs controls. To assess the relationship between the morphological features and autism, we used the receiver operator curves (ROC). In addition, we used recursive partitioning (RP) to determine a specific pattern of abnormalities that is characteristic for the difference between autistic children and typically developing controls. The present findings showed that morphological features are significantly increased in patients with autism. Using ROC and RP, some of the morphological measures also led to strong predictive accuracy. Facial asymmetry, multiple hair whorls and prominent forehead significantly differentiated patients with autism from controls. Future research on multivariable risk prediction models may benefit from the use of morphological features. PMID- 22669540 TI - Diversifying evolution of highly pathogenic H5N1 avian influenza virus in Egypt from 2006 to 2011. AB - An evolutionary analysis was conducted of 354 hemagglutinin (HA) and 208 neuraminidase (NA) genes, including newly generated sequences of 5 HA and 30 NA, of Egyptian H5N1 clade 2.2.1 viruses isolated from poultry and humans. Five distinct phylogenetically distinguishable clusters arose from a monophyletic origin since 2006. Only two clusters remained in circulation after 2009: (i) A cluster of viruses arose in 2007 in industrial-vaccinated chickens and carried multiple mutations in or adjacent to the immunogenic epitopes of the HA. Viruses within this cluster evolved with significantly elevated mutation rates indicating persisting selective pressures, e.g. to escape host immunity and (ii) The second group arose in 2008 and harboured strains from recent human infections featuring a conspicuous deletion in the HA receptor-binding domain and substitutions close to the highly conserved active site of the NA. In both sublineages, a number of positively selected amino acids, different glycosylation patterns and variations in the polybasic proteolytic cleavage site were observed. Continuous monitoring of the evolving H5N1 virus in Egypt is essential to develop new control campaigns in poultry and human population. PMID- 22669541 TI - Complete nucleotide sequence of a South African isolate of Grapevine fanleaf virus. AB - The complete sequences of RNA1 and RNA2 have been determined for a South African isolate of Grapevine fanleaf virus (GFLV-SAPCS3). The two RNAs are, respectively, 7,342 and 3,817 nucleotides in length, excluding the poly(A) tails. RNA1 has a large open reading frame (ORF) of 6,852 nucleotides and a 5'-UTR and a 3'-UTR of 243 and 244 nucleotides, respectively. RNA2 encodes for an ORF of 3,330 nucleotides and has the highest nucleotide identity (90.4 %) with GFLV-F13. The full length nucleotide sequence of GFLV-SAPCS3 RNA1 had the highest nucleotide identity (86.5 %) to the French isolate GFLV-F13. The 5'- and 3'-UTRs of GFLV SAPCS3 RNA2 are 272 nucleotides and 212 nucleotides (nt) in length, respectively. The GFLV-SAPCS3 RNA2 5'-UTR is 32-53 nt longer compared to other GFLV isolates. The GFLV-SAPCS3 RNA2 5'-UTR is also more closely related to GFLV-GHu and Arabis mosaic virus (ArMV) isolates than to other GFLV isolates. Putative intra- and interspecies recombination events between GFLV and ArMV isolates involving GFLV SAPCS3 RNA1 and RNA2 were investigated. Recombination analysis software has indicated that the GFLV-SAPCS3 5'-UTR might have evolved from a recombinational event between GFLV-F13-type and ArMV-Ta-type isolate. PMID- 22669542 TI - The connectivity of lymphogenous and hematogenous tumor cell dissemination: biological insights and clinical implications. AB - Although tumor cells are found in the blood early after tumorigenesis, dissemination through the lymphatic system and in particular the formation of lymph node metastases has long been considered to be a driving force behind the formation of secondary tumors in distant vital organs. Contemporary experimental observations and clinical trial results suggest that this may not be the case. In this review we survey the evidence for both points of view, and examine the hypothesis that the prognostic relevance of lymph node metastases may lie in their ability to indicate that primary tumors are producing soluble factors that have the potential to promote metastasis at these distant sites, for example by releasing tumor cells from dormancy. Furthermore, the interconnectivity between the lymphatic and blood circulatory systems underscores the relevance of the analysis of the properties of circulating and disseminated tumor cells for prognostic evaluation, patient stratification and understanding the biology of metastasis. We therefore give an overview of the current state of the art in this field. PMID- 22669543 TI - Revision anterior cruciate ligament reconstruction: an update. AB - With the rising number of anterior cruciate ligament (ACL) reconstructions performed, revision ACL reconstruction is increasingly common nowadays. A broad variety of primary and revision ACL reconstruction techniques have been described in the literature. Recurrent instability after primary ACL surgery is often due to non-anatomical ACL graft reconstruction and altered biomechanics. Anatomical reconstruction must be the primary goal of this challenging revision procedure. Recently, revision ACL reconstruction has been described using double bundle hamstring graft. Successful revision ACL reconstruction requires an exact understanding of the causes of failure and technical or diagnostic errors. The purpose of this article is to review the causes of failure, preoperative evaluation, graft selection and types of fixation, tunnel placement, various types of surgical techniques and clinical outcome of revision ACL reconstruction. PMID- 22669544 TI - Viscoelastic adaptation of tendon graft material to compression: biomechanical quantification of graft preconditioning. AB - PURPOSE: The tensile viscoelastic behaviour of tendon tissue is of central biomechanical importance and well examined. However, the viscoelastic tendon adaptation to external compression, such as when a tendon graft is fixated with an interference screw, has not been investigated before. Here, we quantify this adaptive behaviour in order to develop a new method to mechanically precondition tendon grafts and to better understand volumetric changes of tendinous tissue. The hypothesis of this study was that under compressive loads, tendon grafts will undergo a temporary volumetric (and therefore diametric) reduction, due to the extrusion of water from the tendon. METHODS: Compressive testing was performed on a material testing machine and load applied through the use of a custom-made mould, with a semi-circular cross section to accommodate the tendon graft. The effects of different compressive forces on the length, diameter and weight of tendon grafts were measured by calipers and a weighing scale, respectively. Further, different strain rates (1 vs. 10 mm/min) (n = 6, per rate), compression method (steady compression vs. creep) (n = 15 for each method) and different compression durations (1, 5, 10 min) (n = 5 for each duration) were tested to identify the most effective combination to reduce graft size by preserving its macroscopic structure. RESULTS: The effect of compression on volume reduction (75 % of initial volume and weight) reached a plateau at 6,000 N on an 8-mm tendon bundle. Length thereby increased by approximately 10 %. Both steady compression and creeping were able to reduce dimensions of the graft; however, creeping was more effective. There was no difference in effect with different durations for compression (p > 0.05) in both methods. CONCLUSION: The viscoelastic behaviour of hamstring tendon grafts under pressure allows preconditioning of the grafts for reduction of volume and diameter and therefore to drill a smaller bone tunnel, retaining more of the original bone. At the same time, the collagen content of the transplant is preserved and a tight fit of the transplant in the bone tunnel achieved. PMID- 22669545 TI - A reformulated spherule-derived coccidioidin (Spherusol) to detect delayed-type hypersensitivity in coccidioidomycosis. AB - The ability of spherule-derived coccidioidin containing 0.4 % phenol and 0.0001 % thimerosal in buffered saline to induce delayed-type hypersensitivity (DTH) was evaluated in four separate studies. The skin test antigen was titrated in 20 adult volunteers with a recent history of pulmonary coccidioidomycosis using intradermal doses of 0.4, 0.8, and 1.6 MUg of antigen, based on total dry weight. Based on these data, a dose of 1.27 MUg was shown to elicit a mean +/- SEM induration response of 23.5 +/- 2.3 mm at 48 h, similar to the 23.6-mm response after 48 h of the U. S. Reference coccidioidin last tested approximately 13 years ago. The 1.27 MUg dose in 0.1 mL of the spherule-derived antigen (Spherusol) was then examined in three separate groups of adult volunteers to determine the sensitivity and specificity of the product. Fifty-nine of 60 individuals living in a non-endemic area for coccidioidomycosis were skin test negative to Spherusol. Twelve subjects with a recent history of pulmonary histoplasmosis were skin test negative to Spherusol. Finally, 51 of 52 individuals with a recent diagnosis of acute pulmonary coccidioidomycosis were skin test positive to Spherusol. Within this group, prior therapy with fluconazole did not appear to reduce the reactivity to Spherusol. No serious adverse events were observed in the four studies. From these data, Spherusol was found to be safe and has an overall observed sensitivity and specificity of >= 98 % in detecting DTH in coccidioidomycosis. PMID- 22669546 TI - Highly crosslinked polyethylene does not reduce aseptic loosening in cemented THA 10-year findings of a randomized study. AB - BACKGROUND: Polyethylene (PE) wear particles are believed to cause aseptic loosening and thereby impair function in hip arthroplasty. Highly crosslinked polyethylene (XLPE) has low short- and medium-term wear rates. However, the long term wear characteristics are unknown and it is unclear whether reduced wear particle burden improves function and survival of cemented hip arthroplasty. QUESTIONS/PURPOSES: We asked whether XLPE wear rates remain low up to 10 years and whether this leads to improved implant fixation, periprosthetic bone quality, and clinical function compared to conventional PE. METHODS: We randomized 60 patients (61 hips) to receive either PE or XLPE cemented cups combined with a cemented stem. At 10 years postoperatively, 51 patients (52 hips) were evaluated for polyethylene wear and component migration estimation by radiostereometry, for radiolucent lines, bone densitometry, and Harris hip and pain scores. Revisions were recorded. RESULTS: XLPE cups had a lower mean three-dimensional wear rate between 2 and 10 years compared to conventional PE hips: 0.005 mm/year versus 0.056 mm/year. We found no differences in cup migration, bone mineral density, radiolucencies, functional scores, and revision rate. There was a trend toward improved stem fixation in the XLPE group. The overall stem failure rate was comparably high, without influencing wear rate in XLPE hips. CONCLUSIONS: XLPE displayed a low wear rate up to 10 years when used in cemented THA, but we found no clear benefits in any other parameters. Further research is needed to determine whether cemented THA designs with XLPE are less prone to stem loosening. LEVEL OF EVIDENCE: Level I, therapeutic study. See the Instructions for Authors for a complete description of levels of evidence. PMID- 22669547 TI - Durability of a cruciate-retaining TKA with modular tibial trays at 20 years. AB - BACKGROUND: Modular tibial trays have been utilized in TKA for more than 20 years. However, concerns have been raised about modular implants and it is unclear whether these devices are durable in the long term. QUESTIONS/PURPOSES: We determined (1) survival, (2) relationship of age and polyethylene thickness with revision, (3) function, and (4) radiographic lucencies and osteolysis in patients having a single TKA implant at 20-year followup. METHODS: We prospectively followed 75 patients implanted with 101 Press-Fit Condylar((r)) (Johnson and Johnson Professional, Inc, Raynham, MA, USA) posterior cruciate retaining TKAs (with modular tibial trays) between 1988 and 1991. At 20 years, 59 patients were deceased. We clinically evaluated the living 16 patients (22 knees) and contacted the relatives of all deceased patients to confirm implant status. We clinically assessed 14 of the 16 patients with the Knee Society score, WOMAC, and UCLA and Tegner activity level scores. Radiographically, we determined lucencies, component migration, and osteolysis. We performed survival analysis including all original patients. Minimum followup was 20 years (mean, 20.6 years; range, 20-21.8 years). RESULTS: Six reoperations were performed in five patients (6% rate of revision) over the 20-year followup. All revisions were related to polyethylene wear and occurred at least 10 years after the primary procedure. Survivorship with revision for any reason as the end point was 91% (95% CI, 0.83 0.97) at 20 years. Average Knee Society clinical and functional scores were 90 (range, 60-100) and 59 (range, 30-87), respectively. CONCLUSIONS: Our data demonstrate the durability of this posterior cruciate-retaining TKA design. The data provide a standard for newer designs and newer bearing surface materials at comparable followup. PMID- 22669548 TI - Clinical and radiographic factors associated with distal radioulnar joint instability in distal radius fractures. AB - BACKGROUND: Distal radioulnar joint (DRUJ) instability is an important cause of ulnar-sided wrist pain in distal radius fractures. However, instability is frequently undiagnosed and the clinical and radiographic factors associated with instability are not well understood. QUESTIONS/PURPOSES: We therefore identified clinical and radiographic factors associated with DRUJ instability in distal radius fractures. PATIENTS AND METHODS: We retrospectively reviewed all 221 patients who underwent surgical treatment for unstable distal radius fractures from 2007 to 2010. Ten patients (five men and five women) had DRUJ instability by intraoperative manual testing (Group I); these patients had a median age of 52 years. The other 211 patients (81 men and 130 women) (Group II) had a median age of 55 years. Clinical and radiographic data were compared between the groups. RESULTS: The incidence of open wounds at the wrist and the relative ulnar length measured on the prereduction radiograph were greater in Group I. An open wound at the wrist and positive ulnar variance of 6 mm or greater on the prereduction radiograph increased the risk of DRUJ instability (relative risks = 45 and 17, respectively) in distal radius fractures. CONCLUSIONS: An open wound at the wrist or positive ulnar variance of 6 mm or greater observed on the prereduction radiograph in patients with distal radius fractures should alert the physician to the possibility of DRUJ instability. LEVEL OF EVIDENCE: Level II, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID- 22669549 TI - Robotic-assisted TKA reduces postoperative alignment outliers and improves gap balance compared to conventional TKA. AB - BACKGROUND: Several studies have shown mechanical alignment influences the outcome of TKA. Robotic systems have been developed to improve the precision and accuracy of achieving component position and mechanical alignment. QUESTIONS/PURPOSES: We determined whether robotic-assisted implantation for TKA (1) improved clinical outcome; (2) improved mechanical axis alignment and implant inclination in the coronal and sagittal planes; (3) improved the balance (flexion and extension gaps); and (4) reduced complications, postoperative drainage, and operative time when compared to conventionally implanted TKA over an intermediate term (minimum 3-year) followup period. METHODS: We prospectively randomized 100 patients who underwent unilateral TKA into one of two groups: 50 using a robotic assisted procedure and 50 using conventional manual techniques. Outcome variables considered were postoperative ROM, WOMAC scores, Hospital for Special Surgery (HSS) knee scores, mechanical axis alignment, flexion/extension gap balance, complications, postoperative drainage, and operative time. Minimum followup was 41 months (mean, 65 months; range, 41-81 months). RESULTS: There were no differences in postoperative ROM, WOMAC scores, and HSS knee scores. The robotic assisted group resulted in no mechanical axis outliers (> +/- 3 degrees from neutral) compared to 24% in the conventional group. There were fewer robotic assisted knees where the flexion gap exceeded the extension gap by 2 mm. The robotic-assisted procedures took an average of 25 minutes longer than the conventional procedures but had less postoperative blood drainage. There were no differences in complications between groups. CONCLUSIONS: Robotic-assisted TKA appears to reduce the number of mechanical axis alignment outliers and improve the ability to achieve flexion-extension gap balance, without any differences in clinical scores or complications when compared to conventional manual techniques. PMID- 22669551 TI - Does extracorporeal shock wave therapy enhance healing of osteochondritis dissecans of the rabbit knee?: a pilot study. AB - BACKGROUND: Severe osteochondritis dissecans (OCD) in children and adolescents often necessitates surgical interventions (ie, drilling, excision, or debridement). Since extracorporeal shock wave therapy (ESWT) enhances healing of long-bone nonunion fractures, we speculated ESWT would reactivate the healing process in OCD lesions. QUESTIONS/PURPOSES: We asked whether ESWT would enhance articular cartilage quality, bone and cartilage density, and histopathology of osteochondral lesions compared to nontreated controls in an OCD rabbit model. METHODS: We harvested a 4-mm-diameter plug of the weightbearing osteochondral surface on the medial femoral condyle of each knee in 20 skeletally immature (8 week-old) female rabbits. We placed a piece of acellular collagen glycosaminoglycan matrix into the cavity and then replaced the plug. Two weeks after surgery, we sedated each rabbit and treated the right knee in a single setting with shock waves: 4000 impulses at 4 Hz and 18 kV. The left knee was a sham control. Ten weeks after surgery, we assessed cartilage morphology of the lesion using a modified Outerbridge Grading System, bone and cartilage density using histologic imaging, bone and cartilage morphology using the histopathology assessment system, and radiographic bone density and union and compared these parameters between ESWT-treated and control knees. RESULTS: Histologically, we observed more mature bone formation and better healing (1.1 versus 3.4) and density of the cartilage (60 versus 49) on the treated side. Radiographically, we noted an increase in bony density (154 versus 138) after ESWT. CONCLUSIONS: ESWT accelerated the healing rate and improved cartilage and subchondral bone quality in the OCD rabbit model. CLINICAL RELEVANCE: This therapeutic modality may be applicable in OCD treatment in the pediatric population. Future research will be necessary to determine whether it may play a role in healing of human osteochondral defects. PMID- 22669552 TI - Is routine mid-term total hip arthroplasty surveillance beneficial? AB - BACKGROUND: Routine followup of patients after primary or revision THA is commonly practiced and driven by concerns that delays in identifying early failure will result in more complicated or more costly surgical interventions. Although mid-term followup (4-10 years) has been performed to follow cohorts of patients, the benefit of observing individual patients regardless of symptoms has not been established. QUESTIONS/PURPOSES: We determined (1) the reasons patients with THA return for mid-term followup, (2) the treatment recommendations and interventions occurring as a result of mid-term followup, and (3) how frequently revision surgery is recommended for asymptomatic and symptomatic patients at mid term followup. METHODS: We retrospectively identified 501 patients (503 hips) who returned for followup at least 4 years (mean, 5 years; range, 4-10.9 years) after their primary or revision THA. We recorded their reasons for followup and treatment recommendations, including those for revision surgery, at mid-term followup. RESULTS: Fifty-three percent of patients returning for routine followup had no symptoms, 31% reported an unrelated musculoskeletal concern, and 19% had symptoms from their primary THA (15%) or revision THA (32%). Sixty-nine percent of symptomatic patients and 10% of asymptomatic patients received treatment recommendations, with physical therapy as the most frequent intervention (74%). Revision surgery was recommended for 6% of symptomatic and 0.6% of asymptomatic patients. CONCLUSIONS: Although routine surveillance may identify rare, asymptomatic patients with arthroplasty failure, it is much more likely to result in recommendations for nonoperative management during early followup. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID- 22669553 TI - Bisphosphonate-associated femur fractures have high complication rates with operative fixation. AB - BACKGROUND: Bisphosphonate-associated femur fractures have been well described but the preoperative patient factors, treatment modalities, and complications of treatment are unclear. QUESTIONS/PURPOSES: We asked whether a diagnosis of osteoporosis, the characteristic radiographic features of bisphosphonate-related femur fractures, and complication rates differed in patients with operatively treated femoral shaft fractures receiving bisphosphonates and in patients not receiving bisphosphonates. METHODS: We retrospectively reviewed 43 patients with bisphosphonate-associated femoral shaft fractures (including subtrochanteric) from 2002 to 2008 and 20 patients with similar fractures but not treated with bisphosphonates. Similar implants were used in both groups, but a greater number of adjuvants were used in the bisphosphonate cohort. We recorded preoperative osteoporosis and radiographic findings of the characteristic bisphosphonate femur fracture and early complications. The minimum followup was 5 months (mean, 29 months; range 5-60 months). RESULTS: Preoperatively a greater percentage of patients treated with bisphosphonates had confirmed osteoporosis than those not treated with bisphosphonates (24% versus 5%, respectively), a greater percentage had a proximal fracture location (48% versus 40%, respectively), and their mean cortex to shaft diameter ratio was greater (24% versus 15%, respectively). The bisphosphonate cohort had a higher rate of intraoperative fractures (21% versus 0%) and postoperative plate failures (30% versus 0%). CONCLUSIONS: Despite low rates of other risk factors and ample use of biologic adjuvants, patients treated with bisphosphonates having femur fractures have more complications. LEVEL OF EVIDENCE: Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence. PMID- 22669554 TI - A case of typical headache with an atypical diagnosis. PMID- 22669555 TI - Aspirin for the primary prevention of cardiovascular diseases. PMID- 22669556 TI - Identification of the biosynthetic gene cluster for the antibiotic polyketide L 155,175 in Streptomyces hygroscopicus. AB - The antibiotic L-155,175, a potent antiparasitic and antifungal compound, has an unusual structure involving 16-membered macrolides that contain a tetrahydropyran ring connected through a three-carbon linker chain. To identify the biosynthetic gene cluster for L-155,175, a genomic DNA library of Streptomyces hygroscopicus ATCC31955 was constructed and screened with a degenerate primer set designed from a conserved region of the ketosynthase (KS) domain. Sequence analysis of a fosmid clone, pEY1D8 (34 kb), revealed multiple open reading frames (ORFs) encoding type I polyketide synthase (PKS). To determine whether the cloned genes are involved in L-155,175 biosynthesis, a deletion mutant (1D8m) was generated by homologous recombination, in which the gene encoding the KS domain was substituted with an apramycin-resistance gene by PCR-targeted Streptomyces gene replacement. LC-MS analysis showed that L-155,175 production was completely abolished in the 1D8m strain, thereby proving that the cloned gene is responsible for L-155,175 biosynthesis. The sequencing of two other fosmid clones (pEY8B10 and pEY1C9) harboring overlapping sequences from pEY1D8 revealed a 60-kb DNA segment encoding six ORFs for type I PKS harboring 12 modules. The domain organization of the PKS modules encoded by PKS exactly matched the structure of L-155,175. This is the first report on the gene cluster involved in the biosynthesis of L-155,175. PMID- 22669557 TI - Health sciences and medical college preadmission criteria and prediction of in course academic performance: a longitudinal cohort study. AB - High School, Aptitude and Achievement Tests have been utilized since 2002 in Saudi Arabia for the purpose of student selection to health sciences and medical colleges. However, longitudinal studies determining the predictive validity of these so-called cognitive tests for in-course performance is lacking. Our aim was to assess the predictive validity of Saudi health sciences and medical school pre admission selection tools for in-course performance over a three year period and therefore we conducted a retrospective review of pre-admission (High School Test, Saudi Aptitude and Achievement tests) and in-course academic performance data (Grade Point Average, GPA) for all students enrolled in undergraduate Health Sciences Colleges and College of Medicine, 2007-2010. Correlation and linear regression analyses were performed for the whole cohort. Data are reported on 87 of 1,905 (4.6 %) students who applied to Health Sciences and Medical Colleges. The results indicate that in-course GPA scores in year three were significantly positively correlated with High School (r = 0.65; p < 0.05), Aptitude (r = 0.65; p < 0.05) and Achievement (r = 0.66; p < 0.05) selection test scores. Furthermore, the High School Exam was the best predictor of achievement in year three. Regression analysis revealed that 54 % of the variance in predicting academic performance is explained by the three test scores. Results confirmed our hypothesis that High School, Aptitude and Achievement tests are statistically predictive of academic performance in health sciences and medical colleges. Further longitudinal, national work is nevertheless required to determine the extent to which pre-admissions cognitive and non-cognitive tests, socio demographic and educational process variables predict undergraduate and postgraduate achievement and performance. PMID- 22669558 TI - Increased serum clearance of oligomannose species present on a human IgG1 molecule. AB - The role of Fc glycans on clearance of IgG molecule has been examined by various groups in experiments where specific glycans have been enriched or the entire spectrum of glycans was studied after administration in pre-clinical or clinical pharmacokinetic (PK) studies. The overall conclusions from these studies are inconsistent, which may result from differences in antibody structure or experimental design. In the present study a well-characterized recombinant monoclonal IgG1 molecule (mAb-1) was analyzed from serum samples obtained from a human PK study. mAb-1 was recovered from serum using its ligand cross-linked to Sepharose beads. The overall purity and recovery of all isoforms were carefully evaluated using a variety of methods. Glycans were then enzymatically cleaved, labeled using 2-aminobenzamide and analyzed by normal phase high performance liquid chromatography. The assays for recovering mAb-1 from serum and subsequent glycan analysis were rigorously qualified at a lower limit of quantitation of 15 MUg/mL, thus permitting analysis to day 14 of the clinical PK study. Eight glycans were monitored and classified into two groups: (1) the oligomannose type structures (M5, M6 and M7) and (2) fucosylated biantennary oligosaccharides (FBO) structures (NGA2F, NA1F, NA2F, NA1F-GlcNAc and NGA2F-GlcNAc). We observed that the oligomannose species were cleared at a much faster rate (40%) than FBOs and conclude that high mannose species should be carefully monitored and controlled as they may affect PK of the therapeutic; they should thus be considered an important quality attribute. These observations were only possible through the application of rigorous analytical methods that we believe will need to be employed when comparing innovator and biosimilar molecules. PMID- 22669559 TI - Postoperative delirium: a 76-year-old woman with delirium following surgery. AB - Delirium (acute confusion) complicates 15% to 50% of major operations in older adults and is associated with other major postoperative complications, prolonged length of stay, poor functional recovery, institutionalization, dementia, and death. Importantly, delirium may be predictable and preventable through proactive intervention. Yet clinicians fail to recognize and address postoperative delirium in up to 80% of cases. Using the case of Ms R, a 76-year-old woman who developed delirium first after colectomy with complications and again after routine surgery, the diagnosis, prevention, and treatment of delirium in the postoperative setting is reviewed. The risk of postoperative delirium can be quantified by the sum of predisposing and precipitating factors. Successful strategies for prevention and treatment of delirium include proactive multifactorial intervention targeted to reversible risk factors, limiting use of sedating medications (especially benzodiazepines), effective management of postoperative pain, and, perhaps, judicious use of antipsychotics. PMID- 22669560 TI - Development of monoclonal antibody-based galactomannoprotein antigen-capture ELISAs to detect Aspergillus fumigatus infection in the invasive aspergillosis rabbit models. AB - Aspergillus fumigatus is one of the most prominent opportunistic fungal pathogens in immunocompromised hosts. Early recognition of this infection along with prompt antifungal therapy may increase the survival rate. We expressed two potential bio markers of A. fumigatus infection-galactomannoprotein Afmp1p and Afmp4p in Pichia pastoris. We generated 33 monoclonal antibodies (MAbs), 20 against recombinant Afmp1p (rAfmp1p) and the other 13 against recombinant Afmp4p (rAfmp4p). Subsequently, we developed two antigen-capture enzyme-linked immunosorbent assays (ELISAs) which employed MAbs as both the capture and the detection antibodies for rAfmp1p and rAfmp4p. The two antigen-capture ELISAs specifically detected Afmp1p/Afmp4p in cultures of A. fumigatus and had no cross-reaction with other tested pathogenic fungi, including Penicillium marneffei and other pathogenic Aspergillus species. The Afmp1p-captured ELISA would be positive even when the culture supernatant of A. fumigatus had been diluted to 128-fold of its original concentration. The two antigen ELISAs could capture circulating or excreted antigens during the acute phase of invasive aspergillosis (IA) in the animal model, and had no cross-reactivity to other Aspergillus-challenged animal models. We developed two antigen-capture ELISAs for the laboratory diagnosis of A. fumigatus infection. These two antigen-capture ELISAs may be useful in the clinical diagnosis of aspergillosis. PMID- 22669561 TI - Comparison of the two blood culture systems, Bactec 9240 and BacT/Alert 3D, in the detection of Candida spp. and bacteria with polymicrobial sepsis. AB - The purpose of this investigation was to evaluate the performance of the Bactec 9240 and BacT/Alert 3D blood culture systems in the detection of Candida spp. and bacteria in simulated polymicrobial sepsis models. A total of 28 clinical isolates of Escherichia coli, Staphylococcus aureus, Candida albicans, and Candida glabrata were studied. Five polymicrobial models of C. albicans + S. aureus, C. albicans + E. coli, C. glabrata + S. aureus, C. glabrata + E. coli, and C. albicans + C. glabrata were prepared. Each combination was inoculated in five different blood culture vials. The two systems were compared for culture positivity and time to detection (TTD). Twenty-four mixed cultures with a yeast and a bacteria were tested. Bactec Mycosis vials could detect yeasts in all 24 cultures. The aerobic vials from both Bactec and BacT/Alert could detect both yeasts and bacteria in 22/24 (91.66 %) cultures. Bactec Plus Anaerobic/F and BacT/Alert FN vials could detect both microorganisms in 19/24 (79.16 %) and 4/24 (16.67 %) vials, respectively. Seven polymicrobial sepsis models with C. albicans + C. glabrata were also tested. Mycosis vials could detect both yeasts in 7/7 mixed cultures. The aerobic vials from Bactec and BacT/Alert could detect both yeasts in 3/7 and 2/7 mixed cultures, respectively. Bactec Plus Aerobic/F had a shorter TTD compared to BacT/Alert FA and Bactec Plus Anaerobic/F vials (p < 0.0001 and p < 0.01, respectively). The present study shows that the Bactec and BacT/Alert systems have different characteristics in the detection of yeasts and bacteria with polymicrobial sepsis. PMID- 22669563 TI - Passive sampling of perfluorinated acids and sulfonates using polar organic chemical integrative samplers. AB - The applicability of a polar organic chemical integrative sampler (POCIS) for detection and determination of perfluorinated acids and sulfonates in water was studied under field conditions. Standard POCIS configurations (i.e., pharmaceutical and pesticide) were deployed in effluent from a wastewater treatment plant for 1, 2, and 3 weeks. Ten of 15 target compounds were found in POCIS, five of which were quantified in wastewater. Pest-POCIS appeared more effective for the sampling, while Pharm-POCIS had a more rapid uptake kinetic, which leads to faster saturation or equilibrium. The results showed that the pesticide configuration is probably more suitable for the sampling of this class of compounds. Based on average concentration in water over the sampling period and amount of compound adsorbed in the POCIS, we calculated sampling rates for five studied compounds and obtained values of 0.034 to 0.222 L day(-1). PMID- 22669562 TI - Acidic pharmaceuticals in domestic wastewater and receiving water from hyper urbanization city of China (Shanghai): environmental release and ecological risk. AB - The occurrence, behavior, and release of five acidic pharmaceuticals, including ibuprofen (IBP), naproxen (NPX), ketoprofen (KEP), diclofenac (DFC), and clofibric acid (CA), have been investigated along the different units in a tertiary-level domestic wastewater treatment plant (WWTP) in hyper-urbanization city of China (Shanghai). IBP was the most abundant chemicals among the measured in raw wastewater. The loads of the acidic pharmaceuticals in the WWTP influent ranged from 7.5 to 414 mg/day/1,000 inh, which were lower than those reported in the developed countries suggesting a less per capita consumption of pharmaceuticals in Shanghai. IBP obtained by highest removal (87 %); NPX and KEP were also significantly removed (69-76 %). However, DFC and CA were only moderately removed by 37-53 %, respectively. Biodegradation seemed to play a key role in the elimination of the studied pharmaceuticals except for DFC and CA. An annual release of acidic pharmaceuticals was estimated at 1,499 and 61.7 kg/year through wastewater and sludge, respectively, from Shanghai. Highest pharmaceuticals concentrations were detected in the effluent discharge point of the WWTP, indicating that WWTP effluent is the main source of the acidic pharmaceuticals to its receiving river. Preliminary results indicated that only DFC in river had a high risk to aquatic organisms. Nevertheless, the joint toxicity effects of these chemicals are needed to further investigate. PMID- 22669564 TI - Cadmium tolerance in six poplar species. AB - Selection of poplar species with greater Cd tolerance and exploiting the physiological mechanisms involved in Cd tolerance are crucial for application of these species to phyto-remediation. The aim of this study is to investigate variation in Cd tolerance among the six poplar species and its underlying physiological mechanisms. Cuttings of six Populus species were cultivated for 10 weeks before exposure to either 0 or 200 MUM CdSO(4) for 20 days. Gas exchange in mature leaves was determined by a portable photosynthesis system. Cd concentrations in tissues were analyzed by a flame atomic absorbance spectrometry. Subsequently, Cd amount per plant, bio-concentration factor (BCF) and translocation factor (T (f)) were calculated. Nonenzymatic compounds and activities of antioxidative enzymes in tissues were analyzed spectrophotometrically. Cd exposure caused decline in photosynthesis in four poplar species including Populus cathayana (zhonghua 1). Among the six species, P. cathayana (zhonghua 1) displayed the highest Cd concentrations in tissues, the largest Cd amount in aerial parts, the highest BCF in aerial parts and T (f) under Cd exposure. Under Cd stress, increases in total soluble sugars in roots but decreases in starch in roots, wood, and leaves of P. cathayana (zhonghua 1) were found. Induced O (2) (*-) and H(2)O(2) production in roots and leaves, and increases in free proline, soluble phenolics, and activities of antioxidative enzymes were observed in P. cathayana (zhonghua 1). Based on results of this pot experiment, it is concluded that P. cathayana (zhonghua 1) is superior to other five species for Cd phyto-remediation, and its well-coordinated physiological changes under Cd exposure confer the great Cd tolerance of this species. PMID- 22669565 TI - Energy reserves and accumulation of metals in the ground beetle Pterostichus oblongopunctatus from two metal-polluted gradients. AB - Living in an area chronically polluted with metals is usually associated with changes in the energy distribution in organisms due to increased energy expenses associated with detoxification and excretion processes. These expenses may be reflected in the available energy resources, such as lipids, carbohydrates, and proteins. In this context, the energy status of Pterostichus oblongopunctatus (Coleoptera: Carabidae) was studied in two metal pollution gradients near Olkusz and Miateczko Slaskie in southern Poland. Both regions are rich in metal ores, and the two largest Polish zinc smelters have been operating there since the 1970s. Beetles were collected from five sites at each gradient. Zinc and cadmium concentrations were measured in both the soil and the beetles. The possible reduction in energy reserves as a cost of detoxifying assimilated metals was evaluated biochemically by determining the total lipid, carbohydrates, and protein contents. At the most polluted sites, the Zn concentration in the soil organic layer reached 2,906 mg/kg, and the Cd concentration reached 55 mg/kg. Body Zn and Cd concentrations increased with increasing soil Zn and Cd concentrations (p = 0.003 and p = 0.0001, respectively). However, no relationship between pollution level and energetic reserves was found. The results suggest that populations of P. oblongopunctatus inhabiting highly metal-polluted sites are able to survive without any serious impact on their energy reserves, though they obviously have to cope with elevated body metal concentrations. PMID- 22669566 TI - Biodegradation and removal of 3,4-dichloroaniline by Chlorella pyrenoidosa based on liquid chromatography-electrospray ionization-mass spectrometry. AB - 3,4-Dichloroaniline (3,4-DCA), widely used in the synthesis of dyes, textile and herbicides, is toxic to living organisms. The purpose of this study was to investigate the capability of green algae in degrading and removing 3,4-DCA in water. An environmentally ubiquitous green alga Chlorella pyrenoidosa was isolated from fresh aquatic environment. Then unicellular alga was incubated with 3,4-DCA at a concentration of 4.6 MUg/ mL in water. The residual concentration of 3,4-DCA in the medium and the metabolites were analyzed. A removal percentage of 78.4 % was obtained over a 7-day period. Two major metabolites with less toxicity were identified as 3,4-dichloroformanilide and 3,4-dichloroacetanilide from the liquid chromatography-electrospray ionization-mass spectrometry analysis. The application of microalga C. pyrenoidosa may have potential for removing the environmental pollutant in aquatic environment. PMID- 22669567 TI - Reduced frequency of NKT-like cells in patients with progressive chronic lymphocytic leukemia. AB - Natural killer T (NKT) cells are a subset of innate immune cells displaying a limited repertoire of antigen specificities and CD1d restriction. Little is known about contribution of NKT cells in cancer initiation and progression. In this study, the frequencies of NKT-like cells, B cells expressing CD1d molecule and CD4(+) regulatory (Treg) cells were analyzed in 40 patients with chronic lymphocytic leukemia (CLL) and 15 healthy subjects by flow cytometry. Our results showed that the frequency of CD3(+)CD56(+) NKT-like cells is significantly decreased in progressive (4.9 +/- 0.8 % of total CD3(+) T cells) compared with indolent (8.1 +/- 1.2 %, p = 0.036) patients and healthy subjects (10.6 +/- 1.7 %, p = 0.003). However, no association was found between NKT-like cell frequency and immunoglobulin heavy chain variable region gene (IGHV) mutation or CD38 and ZAP70 expression. On the other hand, expression of CD1d molecule was significantly higher in leukemic B cells of patients with CLL (75 +/- 1.5 % of total CD19(+) B cells) compared to B cells from healthy subjects (59.6 +/- 2.2 %, p < 0.001), with no significant difference between progressive and indolent patients. Interestingly, the frequency of Treg cells was inversely correlated with that of NKT-like cells in patients with CLL (r = -0.4, p = 0.002). Our results suggest a protective role for NKT-like cells in patients with CLL, which seems to be downregulated presumably by Treg cells. PMID- 22669568 TI - Acute, generalised but transient muscle cramping and weakness shortly after first oxaliplatin infusion. PMID- 22669569 TI - Mechanisms of cadmium-induced proximal tubule injury: new insights with implications for biomonitoring and therapeutic interventions. AB - Cadmium is an important industrial agent and environmental pollutant that is a major cause of kidney disease. With chronic exposure, cadmium accumulates in the epithelial cells of the proximal tubule, resulting in a generalized reabsorptive dysfunction characterized by polyuria and low-molecular-weight proteinuria. The traditional view has been that as cadmium accumulates in proximal tubule cells, it produces a variety of relatively nonspecific toxic effects that result in the death of renal epithelial cells through necrotic or apoptotic mechanisms. However, a growing volume of evidence suggests that rather than merely being a consequence of cell death, the early stages of cadmium-induced proximal tubule injury may involve much more specific changes in cell-cell adhesion, cellular signaling pathways, and autophagic responses that occur well before the onset of necrosis or apoptosis. In this commentary, we summarize these recent findings, and we offer our own perspectives as to how they relate to the toxic actions of cadmium in the kidney. In addition, we highlight recent findings, suggesting that it may be possible to detect the early stages of cadmium toxicity through the use of improved biomarkers. Finally, some of the therapeutic implications of these findings will be considered. Because cadmium is, in many respects, a model cumulative nephrotoxicant, these insights may have broader implications regarding the general mechanisms through which a variety of drugs and toxic chemicals damage the kidney. PMID- 22669570 TI - The minimal impact of food on the pharmacokinetics of ridaforolimus. AB - PURPOSE: Ridaforolimus, a potent inhibitor of the mammalian target of rapamycin (mTOR), is under development for the treatment for solid tumors. This open-label, randomized, 3-period crossover study investigated the effect of food on the pharmacokinetics of ridaforolimus 40 mg as well as safety and tolerability of the study medication. METHODS: Ridaforolimus was administered to 18 healthy, male subjects (mean age 36.4 years) in the fasted state, following ingestion of a light breakfast, and following a high-fat breakfast. Whole blood samples were collected from each subject pre-dose and 1, 2, 3, 4, 6, 8, 24, 48, 72, 96, and 168 h post-dose. RESULTS: The geometric mean (95 % confidence interval, CI) fasted blood area under the curve (AUC(0-infinity)) and maximum concentration (C(max)) were 1940 (1510, 2500) ng h/mL and 116 (87, 156) ng/mL, respectively, and median time to C(max) (T(max)) and average apparent terminal half-life (t(1/2)) were 6.0 and 64.5 h, respectively. Both T(max) and t(1/2) were similar in the fasted and fed states. With a light breakfast, the geometric mean intra individual ratios (GMRs) for AUC(0-infinity) and C(max) (fed/fasted) and 90 % CIs were 1.06 (0.85, 1.32) and 1.15 (0.83, 1.60); following a high-fat breakfast, the AUC(0-infinity) and C(max) GMRs (90 % CI) were 1.46 (1.18, 1.81) and 1.12 (0.81, 1.53), respectively. CONCLUSIONS: Increases in ridaforolimus exposure following both the light and high-fat breakfasts were not considered to be clinically meaningful. Ridaforolimus was generally well tolerated, and there were no discontinuations due to drug-related AEs. Ridaforolimus should be given without regard to food. PMID- 22669571 TI - A multicenter phase II trial of docetaxel and capecitabine as salvage treatment in anthracycline- and taxane-pretreated patients with metastatic breast cancer. AB - OBJECTIVE: To evaluate the efficacy and safety of docetaxel plus capecitabine (DC) combination as salvage treatment in anthracycline- and taxane-pretreated patients with metastatic breast cancer (MBC). PATIENTS AND TREATMENT: Patients with MBC who had disease progression after initial chemotherapy with anthracyclines (n = 29; 100 %) and taxanes (n = 11; 37.9 %) were treated with oral capecitabine 950 mg/m(2) twice daily on days 1-14 and docetaxel 75 mg/m(2) on day 1 every 3 weeks. Nineteen (65.5 %) patients received this regimen as second line and 10 (34.5 %) as >=3rd line of therapy. All patients were evaluable for response and toxicity. RESULTS: Complete response occurred in two (6.9 %) patients and partial response in eleven (37.9 %) for an overall response rate of 44.8 % (95 % CI 26.7-62.9 %). Eleven women (37.9 %) had stable disease and five (17.2 %) progressive disease. Of the eleven patients previously treated with anthracyclines and taxanes, five (45.5 %) responded to DC combination. The median duration of response was 5.7 months (range 3.4-64.2), the median time to disease progression 9.3 months (range 1.2-58), and the median overall survival 25.5 months. No toxic death occurred. Neutropenia grade 4 occurred in 58.6 % of patients and three of them (10.3 %) developed neutropenic fever. Non hematological toxicities were manageable with grade 3 hand-foot syndrome occurring in 6.9 % of the patients, fatigue in 3.4 %, and neurotoxicity in 3.4 %. CONCLUSION: The DC combination is a valuable regimen as salvage treatment in anthracycline- or anthracycline and taxane-pretreated patients with MBC. PMID- 22669572 TI - The anatomical pathways for antennal sensory information in the central nervous system of the cricket, Gryllus bimaculatus. AB - Antennae are one of the major organs to detect chemo- and mechanosensory cue in crickets. Little is known how crickets process and integrate different modality of information in the brain. We thus used a number of different anatomical techniques to gain an understanding of the neural pathways extending from the antennal sensory neurons up to centers in the brain. We identified seven antennal sensory tracts (assigned as T1-7) utilizing anterograde dye filling from the antennal nerve. Tracts T1-T4 project into the antennal lobe (AL), while tracts T5 and T6 course into the dorsal region of the deutocerebrum or the suboesophageal ganglion, and finally, tract T7 terminates in the ventral area of flagellar afferent (VFA). By analyzing autofluorescence images of the AL, we identified 49 sexually isomorphic glomeruli on the basis of shape, relative position and size. On the basis of our sensory-tract data, we assigned the glomeruli into one of four separate groups. We then three-dimensionally reconstructed the internal structures in the AL (glomeruli) and the VFA (layers). Next in the protocerebrum, we identified both the tracts and their terminations from the AL and VFA. We found that 10 tracts originate in the AL, whereas there are at least eight tracts from the VFA. Several tracts from the AL share their routes with those from the VFA, but their termination areas are segregated. We now have a better anatomical understanding of the pathways for the antennal information in cricket. PMID- 22669573 TI - Evaluation of KIR genes in recurrent miscarriage. AB - PURPOSE: Natural killer (NK) cells express killer immunoglobulin-like receptors (KIRs) which recognize HLA class I molecules on trophoblasts. KIRs could either activate NK cells or inhibit them to produce soluble factors necessary for the maintenance of pregnancy, thus they are suspected of being involved in the causes of recurrent miscarriage. The aim of this study was to evaluate whether there is any possible association between KIR genes, genotypes and recurrent miscarriage. METHODS: The present study was carried out on 40 women who had unexplained recurrent miscarriage and 90 controls. Sequence-specific oligonucleotide probes analysis were used to investigate 16 KIR genes. All data were statistically analyzed by Fisher Exact Test. RESULTS: The rate of Bx genotypes that consists elevated number of activating KIR genes was significantly higher (p = 0.014) in women with recurrent miscarriage when compared with the control group. Additionally, the frequency of AA genotype (AA1) of the subjects in the study group was significantly lower than the frequency of the subjects in the control group (p = 0,014). Furthermore, there were no statistically significant differences in the frequencies of the individual KIR genes between women with recurrent miscarriage and the control group. CONCLUSIONS: Inclined balance of KIRs toward an activating state in NK cells may contribute to recurrent miscarriage. PMID- 22669574 TI - The anti-Fn14 antibody BIIB036 inhibits tumor growth in xenografts and patient derived primary tumor models and enhances efficacy of chemotherapeutic agents in multiple xenograft models. AB - Agonistic antibodies targeting Fn14, the receptor for TWEAK, have demonstrated anti-tumor activity in xenograft models. Herein, we further explore the therapeutic potential of the humanized anti-Fn14 agonistic antibody, BIIB036, as a single agent and in combination with standard of care cancer therapeutics. Pharmacokinetic studies of BIIB036 in tumor-bearing mice revealed a half-life of approximately three days suggesting twice a week dosing would be necessary to maintain efficacy. However, in multiple xenograft models, BIIB036 treatment resulted in extended tumor growth inhibition up to 40-50 d following cessation of dosing, suggesting that frequent administration of BIIB036 may not be necessary to maintain prolonged anti-tumor activity. Subsequent xenograft studies revealed that maximal efficacy was achieved with BIIB036 dosing once every two weeks, by either intraperitoneal or subcutaneous administration. Xenograft tumors that were initially treated with BIBI036 and then re-grew up to 1000 mm3 following cessation of the first cycle of treatment remained sensitive to a second cycle of treatment. BIIB036 was also evaluated in patient derived primary colon tumor models, where efficacy compared favorably with a standard of care agent. Lastly, BIIB036 enhanced the efficacy of several standard of care chemotherapeutics, including paclitaxel in MDA-MBA-231 breast tumor xenografts, paclitaxel or carboplatin in HOP62 non-small cell lung xenografts, and 5-FU in NCI-N87 gastric xenografts, with no overlapping toxicities. These studies thus establish BIIB036 as a promising therapeutic agent with durable anti-tumor activity in human xenografts as well as patient derived primary tumor models, and enhanced activity and tolerability in combination with standard of care chemotherapeutics. Taken together, the data presented herein suggest that BIIB036 warrants evaluation in the clinic. PMID- 22669575 TI - AT-406, an orally active antagonist of multiple inhibitor of apoptosis proteins, inhibits progression of human ovarian cancer. AB - Ovarian carcinoma is the most deadly gynecological malignancy. Current chemotherapeutic drugs are only transiently effective and patients with advance disease often develop resistance despite significant initial responses. Mounting evidence suggests that anti-apoptotic proteins, including those of the inhibitor of apoptosis protein (IAP) family, play important roles in the chemoresistance. There has been a recent emergence of compounds that block the IAP functions. Here, we evaluated AT-406, a novel and orally active antagonist of multiple IAP proteins, in ovarian cancer cells as a single agent and in the combination with carboplatin for therapeutic efficacy and mechanism of action. We demonstrate that AT-406 has significant single agent activity in 60% of human ovarian cancer cell lines examined in vitro and inhibits ovarian cancer progression in vivo and that 3 out of 5 carboplatin-resistant cell lines are sensitive to AT-406, highlighting the therapeutic potential of AT-406 for patients with inherent or acquired platinum resistance. Additionally, our in vivo studies show that AT-406 enhances the carboplatin-induced ovarian cancer cell death and increases survival of the experimental mice, suggesting that AT-406 sensitizes the response of these cells to carboplatin. Mechanistically, we demonstrate that AT-406 induced apoptosis is correlated with its ability to down-regulate XIAP whereas AT-406 induces cIAP1 degradation in both AT-406 sensitive and resistance cell lines. Together, these results demonstrate, for the first time, the anti-ovarian cancer efficacy of AT 406 as a single agent and in the combination with carboplatin, suggesting that AT 406 has potential as a novel therapy for ovarian cancer patients, especially for patients exhibiting resistance to the platinum-based therapies. PMID- 22669576 TI - Mesenchymal stem cells in mammary adipose tissue stimulate progression of breast cancer resembling the basal-type. AB - Data are accumulating to support a role for adipose-derived mesenchymal stem cells (MSCs) in breast cancer progression; however, to date most studies have relied on adipose MSCs from non-breast sources. There is a particular need to investigate the role of adipose MSCs in the pathogenesis of basal-like breast cancer, which develops at a disproportionate rate in pre-menopausal African American women with a gain in adiposity. The aim of this study was to better understand how breast adipose MSCs (bMSCs) contribute to the progression of basal like breast cancers by relying on isogenic HMT-3255 S3 (pre-invasive) and T4-2 (invasive) human cells that upon transplantation into nude mice resemble this tumor subtype. In vitro results suggested that bMSCs may contribute to breast cancer progression in multiple ways. bMSCs readily penetrate extracellular matrix components in part through their expression of matrix metalloproteinases 1 and 3, promote the invasion of T4-2 cells and efficiently chemoattract endothelial cells via a bFGF-independent, VEGF-A-dependent manner. As mixed xenografts, bMSCs stimulated the growth, invasion and desmoplasia of T4-2 tumors, yet these resident stem cells showed no observable effect on the progression of pre invasive S3 cells. While bMSCs form vessel-like structures within Matrigel both in vitro and in vivo and chemoattract endothelial cells, there appeared to be no difference between T4-2/bMSC mixed xenografts and T4-2 xenografts with regard to intra- or peri-tumoral vascularity. Collectively, our data suggest that bMSCs may contribute to the progression of basal-like breast cancers by stimulating growth and invasion but not vasculogenesis or angiogenesis. PMID- 22669578 TI - Targeting aminopeptidase N, a newly identified receptor for F4ac fimbriae, enhances the intestinal mucosal immune response. AB - Enterotoxigenic Escherichia coli (ETEC) are a major cause of diarrhea in human and animal. In piglets, ETEC having F4 fimbriae (F4(+) ETEC) induce severe diarrhea, dependent on the presence of receptors for F4 (F4R). In this study, porcine aminopeptidase N (pAPN) was identified as an F4R by comparative proteomic analysis of brush border proteins of F4R(+) and F4R(-) pigs and by adherence/internalization experiments on pAPN-transfected cells. Binding of F4 fimbriae to pAPN depended on sialic acid containing carbohydrate moieties, and resulted in clathrin-mediated endocytosis of the fimbriae. Endocytosis via pAPN was not restricted to F4 fimbriae, but was also observed for anti-pAPN antibodies. Both F4 fimbriae- and pAPN-specific antibodies were taken up in vivo by porcine enterocytes and induced subsequently a rapid immunoglobulin A and G response. In conclusion, we identified pAPN as an endocytotic receptor for F4 fimbriae and highlight the opportunity to target vaccine antigens to this epithelial receptor. PMID- 22669577 TI - Selenium-containing histone deacetylase inhibitors for melanoma management. AB - Melanoma incidence and mortality rates continue to increase each year. Lack of clinically viable agents, drug combinations, effective targeted delivery approaches and success inhibiting targets in tumor tissue have made this disease one of the most difficult to treat, which makes prevention an important option for decreasing disease incidence and mortality rates. Inhibiting histone deacetylases (HDAC) is an approach currently being explored to more effectively treat melanoma but use for prevention has not been explored. In this study, novel selenium containing derivatives of the FDA approved HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) called 5-phenylcarbamoylpentyl selenocyanide (PCP-SeCN) and Bis{5-phenylcarbamoylpentyl} diselenide (B(PCP)-2Se) were created and efficacy tested for preventing early melanocytic lesion development in skin. Topical application of PCP-SeCN and B(PCP)-2Se inhibited melanocytic lesion development in laboratory-generated skin by up to 87% with negligible toxicological effect. Mechanistically, PCP-SeCN and B(PCP)-2Se inhibited HDAC activity and had new inhibitory properties by moderating Akt activity to induce cellular apoptosis as demonstrated by an increase in the sub G0-G1 cell population, and cleaved caspase-3 as well as PARP levels. Furthermore, PCP-SeCN and B(PCP)-2Se inhibited cell proliferation by inhibiting cyclin D1 expression and increasing p21 levels. Thus, PCP-SeCN and B(PCP)-2Se are potential melanoma chemopreventive agents with enhanced efficacy compared with SAHA due to new PI3 kinase pathway inhibitory properties. PMID- 22669580 TI - [Use of SMS to ask mothers to come to vaccination sessions in Bobo-Dioulasso]. AB - Even though the expanded programme for immunization (EPI) coverage at national level is high in Burkina (95% of fully vaccinated children), mothers of children following EPI in Health Centres (HC) would benefit from being reminded of EPI sessions by sending SMS (short message service) to their own mobile phone, or through mobile phone of a family member living in the same compound. SMS could be sent through Computerized Immunization Registers (CIR), hosted by HC computers. 210 mothers of children aged 0 to 5 years were chosen at random and questioned if they owned a mobile phone, if they could read a SMS, or, if not, what language they would understand if a voice SMS was sent. They were also asked if a family member could receive, read and transmit the message, if mothers did not own a mobile phone. They were also asked if they are willing to give their telephone number to HC. 94% of mothers could be reached through written or voice SMS, sent to their own or family member's mobile phone. 100% of mothers would be willing to give their telephone number to their HC to improve their ability to come at the right time for vaccination sessions. SMS reminders, delivered through CIR, should improve EPI attendance and management of sessions in HC, especially in epidemic context. PMID- 22669579 TI - IL-17-producing innate lymphoid cells are restricted to mucosal tissues and are depleted in SIV-infected macaques. AB - Innate lymphoid cells (ILCs) are an emerging subset of lymphocytes involved in surveillance against virally infected cells. Here, we show CD3(-)CD8(high) lymphocytes in macaque blood include major subsets of ILCs including natural killer (NK) cells expressing CD16, NKp46, and NKG2A, but also populations of ILCs in mucosal tissues having different properties. One ILC subset secreted interleukin (IL)-17 (ILC17), but these were restricted to mucosal tissues. Some mucosal ILC17 cells expressed classical NK-cell markers, but little NKG2A or NKG2D. Some ILC17 cells secreted IL-22 and tumor necrosis factor-alpha, but few produced interferon (IFN)-gamma or contained granzyme B. IL-17 production by ILCs was induced by IL-6, transforming growth factor-beta, and IL-23. Further, simian immunodeficiency virus (SIV) infection resulted in a significant loss of ILC17 cells, especially in the jejunum, which persisted throughout SIV infection. These findings indicate that ILC17 cells may be involved in innate mucosal immune responses, and their loss may contribute to loss of intestinal mucosal integrity and disease progression in human immunodeficiency virus (HIV)/SIV infection. PMID- 22669581 TI - [Fixed drug eruption in dermatology setting in Lome (Togo): a retrospective study of 321 cases]. AB - The aim of this study was to determine the frequency and list of drugs responsible for fixed drug eruption (FDE) in Lome (Togo). A descriptive retrospective study of patients with FDE treated from January 2006 to November 2011 in dermatology service at the teaching hospital of Lome (Togo) was conducted. During the study period, 321 cases of FDE were reported among 472 cases of toxidermia observed. Mean age of the patients was 31.27 +/- 14.01 years and sex-ratio (M/F) was 1.01. One hundred thirty-three (41.4%) of 321 patients had a previous FDE, against 58.6% who were in their first attack. The most common form was the hyperpigmented form (247 cases/321). The main locations of the lesions were the trunk (N = 127) followed by the lower limbs (N = 85), the upper limbs (N = 81) and external genital organs (N = 53). A drug was incriminated in 163 (50.8%) of the 321 patients, in whom 109 patients took their drug by self medication. Antibacterial sulfonamides were the first drug involved (70.5%), followed by nonsteroidal anti-inflammatory drugs (9.8%), antimalarial drugs (7.4%) and antibiotics (3.7%). All patients received a banned drug. In addition, 111 patients were treated with antihistamines, 69 with corticosteroids, and 58 with topical antiseptics. During follow-up, 42 of 321 patients have been seen; all had a favorable outcome. Our study confirms the frequency of FDE and the role of antibacterial sulfonamides as the cause of FDE in Africa and documents the effects of self-medication in toxidermia in Togo. PMID- 22669582 TI - Bioactive glass 45S5 powders: effect of synthesis route and resultant surface chemistry and crystallinity on protein adsorption from human plasma. AB - Despite its medical applications, the mechanisms responsible for the osseointegration of bioactive glass (45S5) have yet to be fully understood. Evidence suggests that the strongest predictor for osseointegration of bioactive glasses, and ceramics, with bone tissue as the formation of an apatitic calcium phosphate layer atop the implanted material, with osteoblasts being the main mediator for new bone formation. Most have tried to understand the formation of this apatitic calcium phosphate layer, and other bioresponses between the host and bioactive glass 45S5 using Simulated Body Fluid; a solution containing ion concentrations similar to that found in human plasma without the presence of proteins. However, it is likely that cell attachment is probably largely mediated via the adsorbed protein layer. Plasma protein adsorption at the tissue bioactive glass interface has been largely overlooked. Herein, we compare crystalline and amorphous bioactive glass 45S5, in both melt-derived as well as sol-gel forms. Thus, allowing for a detailed understanding of both the role of crystallinity and powder morphology on surface ions, and plasma protein adsorption. It was found that sol-gel 45S5 powders, regardless of crystallinity, adsorbed 3-5 times as much protein as the crystalline melt-derived counterpart, as well as a greater variety of plasma proteins. The devitrification of melt-cast 45S5 resulted in only small differences in the amount and variety of the adsorbed proteome. Surface properties, and not material crystallinity, play a role in directing protein adsorption phenomena for bioactive glasses given the differences found between crystalline melt-cast 45S5 and sol-gel derived 45S5. PMID- 22669583 TI - Validation of reference genes for normalizing gene expression in real-time quantitative reverse transcription PCR in human thyroid cells in primary culture treated with progesterone and estradiol. AB - The use of appropriately chosen reference genes for normalizing gene expression in real-time quantitative reverse transcription polymerase chain reaction is an important step in the analysis of gene expression, compensating for several technical factors. As female sex hormones have been shown to influence growth and differentiation of thyroid follicular cells, the establishment of normalizer genes in human thyroid cells in primary culture, treated with progesterone, and estradiol, is important to evaluate their effect on gene expression in these cells, so candidate reference genes were studied. beta-Actin, glyceraldehyde-3 phosphate dehydrogenase (GAPDH), beta2-microglobulin (B2M), and TATA box binding protein (TBP) were evaluated in thyroid cells treated with estradiol, progesterone, and their inhibitors. Normfinder software was used to assess the stability of the genes and identified beta-actin as the gene with adequate stability and lower inter-group variations, when compared to TBP, B2M, and GAPDH. PMID- 22669584 TI - The effect of the microgravity rotating culture system on the chondrogenic differentiation of bone marrow mesenchymal stem cells. AB - We investigated the influence of the microgravity rotating culture system on the chondrogenic differentiation of bone marrow mesenchymal stem cells (MSCs). During chondrogenic induction, MSCs combined with polyglycolic acid (PGA) were cultured by static culture or microgravity rotating culture and chondrocyte formation was confirmed by toluidine blue staining. Furthermore, the mRNA and protein expressions of a specific cartilage extracellular matrix protein (collagen type II and Aggrecan) were evaluated by real-time RT-PCR and western blot, respectively. Toluidine blue staining indicated the OD values of proteoglycans semi-determination were higher in the microgravity rotating culture group than the static culture group. Following chondrogenic induction, mRNA and proteins of collagen type II and Aggrecan were more significantly expressed in cells of the microgravity rotating culture group compared with the controls. Compared with routine three-dimensional static culture, the microgravity rotating culture system was more effective for the construction of tissue-engineered cartilage in vitro. PMID- 22669585 TI - Cold response of dedifferentiated barley cells at the gene expression, hormone composition, and freezing tolerance levels: studies on callus cultures. AB - In this study, data is presented how dark-grown, embryogenic barley callus cells respond to cold without any light-dependent, chloroplast-related mechanism, independently of the systemic signals. The expression of HvCBF9, HvCBF14, and HvCOR14b genes, members of one of the most important cold-inducible regulatory system, was measured by real-time PCR. Characteristic of the cold response was similar in the crowns of seedlings and in dark-grown callus cultures, however, gene expression levels were lower in calli. Endogenous concentration of auxins, abscisic acid, and salicylic acid did not change, but phaseic acid and neophaseic acid showed robust accumulation after cold acclimation. Freezing tolerance of the cultures was also higher after 7 days of cold-hardening. The results suggest the presence of a basal, light-independent, cold-responsive activation of the CBF COR14b pathway in barley cultures. The effects of Dicamba, the exogenous auxin analog used for maintaining tissue cultures were also studied. Dicamba seems to be a general enhancer of the gene expression and physiological responses to cold stress, but has no specific effect on the activation. Our data along with previous findings show that this system might be a suitable model for studying certain basic cellular mechanisms involved in the cold acclimation process in cereals. PMID- 22669586 TI - Development of bead-based immunoassay to quantify neutralizing antibody for human papillomavirus 16 and 18. AB - Human papillomavirus (HPV) has drawn great attention globally because of its association with virtually all (99 %) cases of cervical cancer. HPV virus-like particles (VLPs) have been implicated as an effective HPV vaccine candidate. In this study, we optimized the relevant parameters for bacterial production of high risk HPV16 and HPV18 VLP L1 proteins. The combination of glutathione S transferase fusion and late log phase culture induction enhanced the solubility and yield of HPV L1 proteins. For detection and quantification of HPV-16 and -18 antibodies, a Luminex-based competitive immunoassay was developed for use in vaccine clinical trials. The characteristics of the assay that were optimized included monoclonal antibody specificity, conjugation of VLP to microspheres, VLP concentration, antibody concentration, dilution of samples, and incubation time. No cross-reactivity occurred. This immunoassay was proven to be sensitive and accurate, and is potentially valuable for vaccine candidate evaluation and clinical use. PMID- 22669587 TI - Aortic root compliance influences hemolysis in mechanical heart valve prostheses: an in-vitro study. AB - Mechanical heart valve prostheses are known to activate coagulation and cause hemolysis. Both are particularly dependent on the leaflet dynamics, which in turn depends on the flow field in the aortic root influenced by the aortic root geometry and its compliance. Compliance reduction of large vessels occurs in aging patients, both in those who have atherosclerotic diseases and those who do not. In this study we investigated the correlation between hemolysis and the compliance of the proximal aorta in a novel, pulsatile in vitro blood tester using porcine blood. Two mechanical heart valves, the St Jude Medical (SJM) bileaflet valve and a trileaflet valve prototype (Triflo) were tested for hemolysis under physiological conditions (120/80 mm Hg, 4.5 l/min, 70 bpm) and using two different tester setups: with a stiff aorta and with a compliant aorta. Valve dynamics were subsequently analyzed via high-speed videos. In the tests with the Triflo valve, the free plasma hemoglobin increased by 13.4 mg/dl for the flexible and by 19.3 mg/dl for the stiff setup during the 3-hour test. The FFT spectra and closing speed showed slight differences for both setups. Free plasma hemoglobin for the SJM valve was up by 22.2 mg/dl in the flexible and 42.7 mg/dl in the stiff setup. Cavitation induced by the higher closing speed might be responsible for this, which is also indicated by the sound spectrum elevation above 16 kHz. PMID- 22669589 TI - Nonlinear analysis of heart rate variability to assess the reaction of ewe fetuses undergoing fetal cardiac surgery. AB - Fetal cardiac surgery (FCS) represents a challenging issue for the in utero treatment of congenital heart defects. However, FCS has still not gained the sufficient reliability for clinical practice due to an incompletely elucidated fetal stress response. For example, blood sampling can contribute to its onset, leading to fetoplacental unit dysfunction, one of the main causes of failure of the surgical procedure. In order to address this issue, the role of the autonomic control system during an experimental procedure of cardiac bypass on ewe fetuses was investigated by means of recurrence quantification analysis (RQA), a well recognized method for the analysis of nonlinear systems. RQA was applied to time series extracted from fetal arterial pressure recordings before and after the cardiac bypass established by means of an extracorporeal circuit, including an axial blood pump, and taking advantage of the capability of the placenta to work as a natural oxygenator. Statistically significant correlations were found among RQA-based metrics and fetal blood gas data, suggesting the possibility to infer the clinical status of the fetus starting from its hemodynamic signals.This study shows the relevance of RQA as a complementary tool for the monitoring of the fetal status during cardiac bypass. PMID- 22669588 TI - Divert to ULTRA: differences in infused volumes and clearance in two on-line hemodiafiltration treatments. AB - BACKGROUND: Mixed diffusive-convective dialysis therapies offer greater removal capabilities than conventional dialysis. The aim of this study was to compare two different on-line, post-dilution hemodiafiltration (HDF) treatments with regard to achieved convective volume and middle-molecule dialysis efficiency: standard volume control (sOL-HDF) and automated control of the transmembrane pressure (TMP) (UC-HDF). METHODS: We enrolled 30 ESRD patients (55.9 +/- 14.0 years, 20/10 M/F) in a randomized, prospective, cross-over study. The patients received a 3 month period of sOL-HDF followed by UC-HDF for a further 3 months, or vice versa, using the same dialysis machine. In sOL-HDF, fixed exchange volumes were set according to a filtration fraction greater than or equal to 25%. In UC-HDF therapy, the exchanged volume was driven by a biofeedback system controlling the TMP and its set point in a double loop. Patients maintained their treatment time, dialyzer, blood flow rate, and anticoagulant regimen unchanged throughout the study. RESULTS: Greater convective volumes were achieved in UC-HDF than in sOL HDF (23.8 +/- 3.9 vs.19.8 +/- 4.8 L; p<0.001) with high pre-dialysis Ht value (sOL-HDF 34.0 +/- 4.5% and UC-HDF 34.0 +/- 4.4%; p = 0.91). The average clearance values of beta2m and P were higher in UC-HDF than in sOL-HDF (respectively 123 +/ 24 vs. 111 +/- 22 ml/min, p<0.002 and 158 +/- 26 vs. 152 +/- 25 ml/min, p<0.05). Moreover, the UC-HDF mode led to a significantly increased rate of call-free sessions from 88% to 97% (p<0.0001). CONCLUSIONS: This study showed that the biofeedback module, applied to the automatic control of TMP in on-line HDF, results in higher convective volumes and correspondingly higher beta2m and P clearances. By making the HDF treatment more automated and less complex to perform, it significantly reduced the staff workload. PMID- 22669590 TI - Changes in whole blood viscosity at low shear rates correlate with intravascular volume changes during hemodialysis. AB - BACKGROUND: Elevated blood viscosity has been shown to be independently correlated with cardiovascular risk factors and associated with increased risk of major cardiovascular events, including death and acute myocardial infarction. The aim of the present study was to investigate changes in whole blood viscosity (WBV) at shear rates of 1, 5, and 300 s-1 before and after hemodialysis in patients with end-stage renal disease (ESRD). We also examined the relationship between the changes of WBV and intravascular blood volume. METHODS: 43 patients with ESRD receiving maintenance hemodialysis were enrolled. WBV was measured using a scanning capillary tube viscometer pre- and post-dialysis to quantify dialytic viscosity surges. Body weight, blood pressure, and hematocrit were also measured before and after hemodialysis, as was the fluid removed during the session. RESULTS: Hemodialysis had a 3 times greater impact on the low-shear WBV at a shear rate of 1 s-1 (i.e., 44.1% change) than on the high-shear WBV at a shear rate of 300 s-1 (i.e., 15.9% change). Changes in the low-shear WBV obtained at shear rates of 1 and 5 s-1 during hemodialysis were significantly correlated with changes in hematocrit. The intravascular blood volume reduction during hemodialysis was positively correlated with the changes in both high-shear and low-shear WBVs. CONCLUSIONS: These results suggest that the WBV parameter may hold additional information beyond hemoconcentration. Further research is needed to evaluate the relationship between low-shear WBV surges and increased morbidity in the patient population with ESRD. PMID- 22669591 TI - Partially hydrolyzed guar gums reduce dietary fatty acid and sterol absorption in guinea pigs independent of viscosity. AB - This study investigated the effect of two partially hydrolyzed guar gums (PHGG) on fatty acid and sterol excretion. PHGG were obtained by chemical hydrolysis of guar gum (GG) with H(2)O:EtOH (1:1) at 100 degrees C for 1 h (PHGG1) or 2 h (PHGG2). The viscosity of the PHGG in a 1 % (w/v) aqueous solution corresponded to that of a pseudoplastic fluid and was higher for PHGG1 than PHGG2. Guinea pigs (n = 8 per group) were fed high fat diets (17/100 g) that contained 12/100 g of cellulose, PHGG1, or PHGG2 for 4 weeks. Despite the differences in viscosity, the two PHGG exerted similar physiological effects. Compared to the control cellulose group, the body weight gain was lower in animals fed PHGG, although no effect on food consumption was observed. PHGG increased the excretion of fatty acids and neutral sterols, but not bile acids. Consumption of PHGG did not alter the fecal fatty acid profile, while intestinal bioconversion of sterols tended to increase in response to PHGG2. A reduction in the viscosity within the range tested did not correlate with losses in the hypocholesterolemic capacity of PHGG as both were effective in reducing plasma cholesterol. Thus, we conclude that the chemical hydrolysis of guar gum renders the gum suitable for inclusion in food products without significantly altering its beneficial health effects. PMID- 22669592 TI - Cerebral blood flow and cerebrovascular reactivity at rest and during sub-maximal exercise: effect of age and 12-week exercise training. AB - Chronic reductions in cerebral blood flow (CBF) and cerebrovascular reactivity to CO2 are risk factors for cerebrovascular disease. Higher aerobic fitness is associated with higher CBF at any age; however, whether CBF or reactivity can be elevated following an exercise training intervention in healthy individuals is unknown. The aim of this study was to assess the effect of exercise training on CBF and cerebrovascular reactivity at rest and during exercise in young and older individuals. Ten young (23 +/- 5 years; body mass index (BMI), 26 +/- 3 kg m(-2); [Formula: see text], 35 +/- 5 ml kg(-1) min(-1)) and 10 older (63 +/- 5 years; BMI, 25 +/- 3.0 kg m(-2); [Formula: see text], 26 +/- 4 ml kg(-1) min(-1)) previously sedentary individuals breathed 5 % CO2 for 3 min at rest and during steady-state cycling exercise (30 and 70 % heart rate range (HRR)) prior to and following a 12-week aerobic exercise intervention. Effects of training on middle cerebral artery blood velocity (MCAv) at rest were unclear in both age groups. The absolute MCAv response to exercise was greater in the young (9 and 9 cm s(-1) (30 and 70 % HRR, respectively) vs. 5 and 4 cm s(-1) (older), P < 0.05) and was similar following training. Cerebrovascular reactivity was elevated following the 12-week training at rest (2.87 +/- 0.76 vs. 2.54 +/- 1.12 cm s(-1) mm Hg(-1), P = 0.01) and during exercise, irrespective of age. The finding of a training-induced elevation in cerebrovascular reactivity provides further support for exercise as a preventative tool in cerebrovascular and neurological disease with ageing. PMID- 22669593 TI - Association of sleep quality and dementia among long-lived Chinese older adults. AB - In this study, we examined the existence of relationship between sleep quality and dementia in subjects aged 90 years and above. The sample included 216 men and 444 women. Dementia and sleep quality were measured with 30-item mini-mental state examination (MMSE) and the Pittsburgh sleep quality index, respectively. Subjects with dementia had higher sleep quality score (7.83 +/- 2.15 vs. 5.22 +/- 2.49; P < 0.0001), longer sleep latency (50.97 +/- 21.33 vs. 37.61 +/- 12.53; P < 0.0001), and a lower sleep efficiency percentage (73.95 +/- 8.783 vs. 81.32 +/- 10.21; P < 0.0001) and more likely to report poor sleep quality (25.42 vs.17.13 %; P = 0.035). Subjects with poor sleep quality had significantly lower MMSE scores (P = 0.007) and higher prevalence of dementia (P = 0.042). Multiple logistic regressions were performed by adjusting clinical factors that are thought to be associated with dementia or sleep quality. We found that poor sleep quality was a risk factor for dementia (unadjusted odds ratio (OR) 1.719, 95 % confidence interval (CI) 1.138-2.597; adjusted OR 1.759, 95 % CI 1.012-3.057). There was no significant difference in MMSE scores (11.25 +/- 3.40, 16.26 +/- 5.14, and 15.43 +/- 5.51; P = 0.105) among participants with daily average sleep durations of <5, 5-9, and >9 h, respectively. Among Chinese nonagenarians and centenarians, dementia was correlated with poor sleep quality, longer sleep latency, and lower sleep efficiency percentage. PMID- 22669594 TI - Ditosylate salt of itraconazole and dissolution enhancement using cyclodextrins. AB - Salt formation has been a promising approach for improving the solubility of poorly soluble acidic and basic drugs. The aim of the present study was to prepare the salt form of itraconazole (ITZ), a hydrophobic drug to improve the solubility and hence dissolution performance. Itraconazolium ditolenesulfonate salt (ITZDITOS) was synthesized from ITZ using acid addition reaction with p toluenesulfonic acid. Salt characterization was performed using (1)H NMR, mass spectrometry, Fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction. The particle size and morphology was studied using dynamic light scattering technique and scanning electron microscopy, respectively. The solubility of the salt in water and various pharmaceutical solvents was found multifold than ITZ. The dissolution study exhibited 5.5-fold greater percentage release value in 3 h of ITZDITOS (44.53%) as compared with ITZ (8.54%). Results of in vitro antifungal studies using broth microdilution technique indicate that ITZDITOS possessed similar antifungal profile as that of ITZ when tested against four fungal pathogens. Furthermore, the physical mixtures of ITZDITOS with two cyclodextrins, beta-cyclodextrin (beta-CD), and 2 hydroxypropyl-beta-cyclodextrin (HP-beta-CD) were prepared in different molar ratios and were evaluated for in vitro release. It was observed that in only 30 min of dissolution study, about 74 and 81% of drug was released from 1:3 molar ratios of ITZDITOS with beta-CD and ITZDITOS with HP-beta-CD, respectively, which was distinctly higher than the drug released from ITZ commercial capsules (70%). The findings warrant further preclinical and clinical studies on ITZDITOS so that it can be established as an alternative to ITZ for developing oral formulations. PMID- 22669595 TI - Affect regulation and HIV risk among youth in therapeutic schools. AB - The acquisition of affect regulation skills is often impaired or delayed in youth with mental health problems but the relationship between affect dysregulation and risk behaviors has not been well studied. Baseline data from adolescents (N = 417; ages 13-19) recruited from therapeutic school settings examined the relationship between affect dysregulation, substance use, self-cutting, and sexual risk behavior. Analyses of covariance demonstrated that adolescents who did not use condoms at last sex, ever self-cut, attempted suicide, used alcohol and other drugs and reported less condom use self-efficacy when emotionally aroused were significantly more likely (p < .01) to report greater difficulty with affect regulation than peers who did not exhibit these behaviors. General patterns of difficulty with affect regulation may be linked to HIV risk behavior, including condom use at last sex. HIV prevention strategies for youth in mental health treatment should target affect regulation in relation to multiple risk behaviors. PMID- 22669596 TI - Significant improvement in MRI-proven bone edema is associated with protection from structural damage in very early RA patients managed using the tight control approach. AB - OBJECTIVE: To identify the value of magnetic resonance imaging (MRI)-proven bone edema in patients with very early rheumatoid arthritis (RA). METHODS: All of the 13 patients included in the study were positive at entry for MRI-proven bone edema of the wrist and finger joints and anti-cyclic citrullinated peptide antibodies or IgM-rheumatoid factor. A tight control approach was applied for 12 months. Plain MRI and radiographs of both wrist and finger joints were examined every 6 months. MRI was scored by the RA MRI scoring (RAMRIS) technique and plain radiographs were scored using the Genant-modified Sharp score. Variables that were correlated with plain radiographic changes at 12 months were examined. RESULTS: Simplified disease activity index (SDAI) remission was achieved in 7 patients, and a significant reduction in the RAMRIS bone edema score, which declined to <33 % as compared with the baseline, was achieved in 8 out of 13 patients. Four patients showed plain radiographic progression while 9 patients did not. Significant reductions in the RAMRIS bone edema score (p = 0.007) and the time-integrated SDAI (p = 0.031) were the variables involved in plain radiographic progression. CONCLUSIONS: Improvement in bone edema may be associated with protection against structural damage in very early RA patients managed using the tight control approach. PMID- 22669597 TI - Fluorodeoxyglucose (FDG) uptake in pulmonary rheumatoid nodules diagnosed by video-assisted thoracic surgery lung biopsy: two case reports and a review of the literature. AB - Two cases of rheumatoid nodules evaluated by fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and video-assisted thoracic surgery (VATS) biopsy are reported. The first case was that of a 44-year-old woman who presented with a cavitated nodule with intense standardized uptake values (SUVs) both in the early (max 3.4) and delayed (max 4.4) phases, suggesting malignancy. However, after VATS biopsy, she was diagnosed as having a rheumatoid nodule with vasculitis. The second case was that of a 74-year-old woman admitted with bilateral lung nodules, two of which showed intense early (max 2.2) and delayed (max 6.0) phase SUVs, and mild early (max 0.6) and delayed (max 0.9) phase SUVs. These two nodules were finally proven to be a lung cancer and rheumatoid nodule without vasculitis, respectively. These cases show that rheumatoid nodules with an enhanced inflammatory process, such as vasculitis, can appear false-positive for malignancy on FDG-PET/CT scan images. PMID- 22669598 TI - Subacute thyroiditis in a patient with juvenile idiopathic arthritis undergoing etanercept treatment: a case report and review of the literature. AB - We report on a 24-year-old woman with juvenile idiopathic arthritis (JIA) who developed subacute thyroiditis (SAT) while being treated with etanercept. She had suffered from JIA for 12 years, and her arthritis proved refractory to treatment with ibuprofen, prednisolone, and methotrexate. For the past 5 years, the patient had been treated successfully with etanercept at 25 mg/week. The patient more recently complained of high fever and lassitude, and presented with anterior neck swelling and tenderness. Palpation of the thyroid gland revealed it to be warm, erythematous, tender, and diffusely swollen. Laboratory tests revealed an increased erythrocyte sedimentation rate and C-reactive protein level. Thyroid function tests revealed decreased levels of thyrotropin-stimulating hormone, increased levels of free triiodothyronine, free thyroxine, and thyroglobulin, and an absence of thyroid autoantibodies. Sonography showed a diffusely reduced predominantly hypoechoic thyroid gland. Unenhanced computed tomography of the neck showed a homogeneously and mildly reduced thyroid gland. Serum titers of several viruses were not significant and so were considered unlikely to be the pathogens. On the basis of these presented findings, we diagnosed SAT, and etanercept therapy was withdrawn. The patient was treated with antibiotics and an increased prednisolone dose was initiated. She became symptom free and showed improved laboratory test results within 2 weeks, and was euthyroid by 3 months. Three months later, the patient developed hypothyroidism, although 6 months further on, the patient was asymptomatic on prednisolone, methotrexate, and levothyroxine therapy. In conclusion, whether SAT is a specific adverse event in this case in response to etanercept remains unclear. Nevertheless, the possibility of SAT should be considered in such patients on etanercept treatment. PMID- 22669599 TI - Mortality factors in idiopathic inflammatory myopathy: focusing on malignancy and interstitial lung disease. AB - OBJECTIVES: The objective of this study was to assess the incidence and common types of concomitant malignancies and to define predictive factors of death in Korean patients with idiopathic inflammatory myopathy (IIM). METHODS: From January 1989 to May 2011, 162 patients were diagnosed with IIM at a university hospital in Korea. The medical records were retrospectively reviewed. The clinical findings of the patients were compared for malignancy, and the prognostic factors predicting death were analyzed. RESULTS: Malignancies were found in 17 patients (10.5 %), all of whom had a significantly lower frequency of interstitial lung disease (ILD) and an older age at onset. The main causes of death were ILD and malignancy. Older age at diagnosis, presence of malignancy, rapidly progressive ILD and minimal creatinine phosphokinase (CPK) elevation were independent risk factors for death. CONCLUSIONS: Malignancy was one of the most serious risk factor for death in our patients with IIM. Early discovery of malignancy is important, and an extensive investigation for common malignancies in each region should be done at diagnosis and for a minimum of 2 years thereafter. As minimally elevated CPK levels in ILD patients may be associated with fatal ILD, an early evaluation and a more aggressive treatment of ILD should be considered in these patients. PMID- 22669600 TI - Improvement of health status evaluated by Arthritis Impact Measurement Scale 2 (AIMS-2) and Short Form-36 (SF-36) in patients with rheumatoid arthritis treated with tocilizumab. AB - OBJECTIVE: To evaluate the improvement of health status in patients with rheumatoid arthritis (RA) treated with tocilizumab. METHODS: Thirty-nine patients were treated with 8 mg/kg tocilizumab every 4 weeks for 24 weeks. Disease activity was assessed by Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI). Improvement of health status was assessed by Arthritis Impact Measurement Scale 2 (AIMS-2) and Short Form-36 (SF-36). RESULTS: Tocilizumab improved CDAI and SDAI significantly at week 4 compared with at baseline. In the components of AIMS-2, "physical score", "symptom" and "affect" improved significantly at week 4 compared with at baseline, while "social interaction" did not improve significantly during 24 weeks of tocilizumab therapy. Similarly in SF-36, "bodily pain", "general health", "vitality" and "mental health" improved significantly at week 4. The most correlative component of AIMS-2 with CDAI was "symptom", while "social interaction" did not correlate with CDAI during tocilizumab treatment. CONCLUSION: The time-course diversity in improvement of health status should be considered to provide proper healthcare when treated with tocilizumab. PMID- 22669601 TI - Comment on "Comparison of MMP-3 levels in rheumatoid arthritis after treatment with tocilizumab or infliximab for 12 weeks" by Yokoe et al. PMID- 22669602 TI - Relationships of diverse apoptotic death process patterns to mitochondrial membrane potential (Deltapsi(m)) evaluated by three-parameter flow cytometric analysis. AB - Recently, it has been proposed that novel methodologies are needed to re-evaluate apoptotic cell death, as studies of apoptosis have shown it to be a complex process. Since mitochondria are key regulators in cell death pathways, we developed a simultaneous 3-parameter flow cytometric analysis that incorporates the change in mitochondrial membrane potential (Deltapsi(m)) in an Annexin-V [for phosphatidyl-serine (PS)] and propidium iodide (PI) assay system (3 parameters with 4 colours), and evaluated the apoptotic process using various haematological malignant cell lines and death triggers. The present method enabled visualization of cell composition during apoptosis and captured complicated molecular events. For example, apoptotic cells that lost Deltapsi(m) did not always externalize PS, while some late apoptotic cells had polarized Deltapsi(m). The findings of unchanged PS-externalization and aberrant cell death suggest that there is no relationship of PS externalization and apoptosis with an unknown apoptotic mechanism. Based on PS-externalization, sensitivity to staurosporine, and the combination of cell lines and triggers, the apoptotic process was classified into 2 types. Importantly, most of our findings could not be observed by PS-PI and Deltapsi(m) assays when independently performed. Our method may be useful for examining mitochondrial-related apoptosis and death signalling pathways, as well as screening novel apoptosis-inducing cancer drugs. PMID- 22669603 TI - Inhibitory effect of tannins from galls of Carpinus tschonoskii on the degranulation of RBL-2H3 Cells. AB - In this study, the anti-allergy potency of thirteen tannins isolated from the galls on buds of Carpinus tschonoskii (including two tannin derivatives) was investigated. RBL-2H3 (rat basophilic leukemia) cells were incubated with these compounds, and the release of beta-hexosaminidase and cytotoxicity were measured. Of the thirteen tannins, tetragalloylglucose (2), pentagalloylglucose (3), casuarictin (4), and casuarinin (9) were the most potent inhibitors, and all the tannins showed no cytotoxic effect after 24 h of incubation. The results obtained suggest that tannins from C. tschonoskii are capable of inhibiting allergic reactions and may be useful for the treatment or prevention of type I allergic diseases. PMID- 22669604 TI - Preface. PMID- 22669605 TI - Regulation of anthocyanin biosynthesis by nitrogen in TTG1-GL3/TT8-PAP1 programmed red cells of Arabidopsis thaliana. AB - Nitrogen nutrients can regulate anthocyanin biosynthesis in Arabidopsis thaliana. In this investigation, we report the nitrogen regulation of anthocyanin biosynthesis activated by TTG1-GL3/TT8-PAP1 in red pap1-D cells. To understand the mechanisms of nitrogen regulation, we employed red pap1-D cells and wild-type cells (as a control) to examine the effects of different nitrogen treatments on anthocyanin biosynthesis. In general, the higher concentrations of ammonium and high total nitrogen tested (e.g., 58.8 and 29.8 mM total nitrogen consisting of NH(4)NO(3) and KNO(3)) reduced the levels and molecular diversity of anthocyanins; in contrast, the lower concentrations of ammonium and total nitrogen conditions (e.g., 9.4 mM KNO(3) and the depletion of nitrogen) increased the levels and molecular diversity of anthocyanins. An expression analysis of the main regulatory and pathway genes showed that at conditions of higher concentrations of ammonium and total nitrogen, the expression levels of PAP1 and TT8 decreased, but the expression levels of LBD37, 38 and 39, three negative regulators of anthocyanin biosynthesis, increased. In addition, the expression levels of the main pathway genes decreased. In contrast, at conditions of lower concentrations of ammonium and total nitrogen, the expression levels of PAP1, TT8 and the main pathway genes increased, whereas those of LBD37, 38 and 39 decreased. These results show that nitrogen regulation of anthocyanin biosynthesis in red cells undergoes a mechanism by which nitrogen controls the expression of genes encoding both main components of the TTG1-GL3/TT8-PAP1 complex and negative regulators. Based on these observations, we propose that the regulatory mechanism of nitrogen may occur via two pathways to control the expression of genes encoding positive and negative regulators in red pap1-D cells. PMID- 22669607 TI - Abstracts of the 2012 International MASCC/ISOO (Multiple Association of Supportive Care in Cancer/International Society for Oral Oncology) Symposium. New York City, New York, USA. June 28-30, 2012. PMID- 22669606 TI - Effect of ring-substituted oxysterols on the phase behavior of dipalmitoylphosphatidylcholine membranes. AB - Oxysterols are oxygenated derivatives of cholesterol that form a class of potent regulatory molecules with diverse biological activity. Given the implications of oxysterols in several physiological/pathophysiological pathways of human diseases, it is important to identify how their presence affects the biophysical properties of cell membranes. In this article we first describe the structure, formation, and biological functions of oxysterols, and previous work on the effect of these molecules on the structure and phase behavior of lipid membranes. We then present results of our X-ray diffraction experiments on aligned multilayers of dipalmitoylphosphatidylcholine (DPPC) membranes containing ring substituted oxysterols. The effect of these molecules on the phase behavior of DPPC membranes is found to be very similar to that of cholesterol. All the oxysterols studied induce a modulated phase in DPPC membranes, similar to that reported in DPPC-cholesterol membranes. However, some differences are observed in the ability of these molecules to suppress the main transition of the lipid and to induce chain ordering, which might be related to differences in their orientation in the bilayer. PMID- 22669609 TI - Optic neuropathy associated with spontaneous intracranial hypotension. AB - Spontaneous intracranial hypotension is characterized by postural headache that is generally associated with neck and/or back pain, radicular symptoms, nausea, and vomiting, and can sometimes be accompanied by cranial nerve symptoms. Although ocular manifestations are common, visual impairment due to optic nerve involvement is not commonly reported. Here, we report a case of a 34-year-old woman with postural headache and visual loss in the left eye associated with spontaneous intracranial hypotension. The orbital magnetic resonance imaging revealed increased intensity on T2-weighted images and on the pathologic contrast enhancement of the left optic nerve. Radionuclide cisternography showed bilateral cerebrospinal fluid leakage at the top of the thoracic region. To our knowledge, this is the first report documenting an association between optic neuropathy and spontaneous intracranial hypotension. PMID- 22669608 TI - The English and Chinese versions of the five-level EuroQoL Group's five-dimension questionnaire (EQ-5D) were valid and reliable and provided comparable scores in Asian breast cancer patients. AB - OBJECTIVE: To examine the measurement properties of and comparability between the English and Chinese versions of the five-level EuroQoL Group's five-dimension questionnaire (EQ-5D) in breast cancer patients in Singapore. METHODS: This is an observational study of 269 patients. Known-group validity and responsiveness of the EQ-5D utility index and visual analog scale (VAS) were assessed in relation to various clinical characteristics and longitudinal change in performance status, respectively. Convergent and divergent validity was examined by correlation coefficients between the EQ-5D and a breast cancer-specific instrument. Test-retest reliability was evaluated. The two language versions were compared by multiple regression analyses. RESULTS: For both English and Chinese versions, the EQ-5D utility index and VAS demonstrated known-group validity and convergent and divergent validity, and presented sufficient test-retest reliability (intraclass correlation = 0.72 to 0.83). The English version was responsive to changes in performance status. The Chinese version was responsive to decline in performance status, but there was no conclusive evidence about its responsiveness to improvement in performance status. In the comparison analyses of the utility index and VAS between the two language versions, borderline results were obtained, and equivalence cannot be definitely confirmed. CONCLUSION: The five-level EQ-5D is valid, responsive, and reliable in assessing health outcome of breast cancer patients. The English and Chinese versions provide comparable measurement results. PMID- 22669610 TI - Treatment of facial myokymia in multiple sclerosis with botulinum toxin. PMID- 22669611 TI - Emerging of cysticercosis in Europe: a concern. PMID- 22669612 TI - BDNF and DYRK1A are variable and inversely correlated in lymphoblastoid cell lines from Down syndrome patients. AB - Down syndrome or trisomy 21 is the most common genetic disorder leading to mental retardation. One feature is impaired short- and long-term spatial memory, which has been linked to altered brain-derived neurotrophic factor (BDNF) levels. Mouse models of Down syndrome have been used to assess neurotrophin levels, and reduced BDNF has been demonstrated in brains of adult transgenic mice overexpressing Dyrk1a, a candidate gene for Down syndrome phenotypes. Given the link between DYRK1A overexpression and BDNF reduction in mice, we sought to assess a similar association in humans with Down syndrome. To determine the effect of DYRK1A overexpression on BDNF in the genomic context of both complete trisomy 21 and partial trisomy 21, we used lymphoblastoid cell lines from patients with complete aneuploidy of human chromosome 21 (three copies of DYRK1A) and from patients with partial aneuploidy having either two or three copies of DYRK1A. Decreased BDNF levels were found in lymphoblastoid cell lines from individuals with complete aneuploidy as well as those with partial aneuploidies conferring three DYRK1A alleles. In contrast, lymphoblastoid cell lines from individuals with partial trisomy 21 having only two DYRK1A copies displayed increased BDNF levels. A negative correlation was also detected between BDNF and DYRK1A levels in lymphoblastoid cell lines with complete aneuploidy of human chromosome 21. This finding indicates an upward regulatory role of DYRK1A expression on BDNF levels in lymphoblastoid cell lines and emphasizes the role of genetic variants associated with psychiatric disorders. PMID- 22669613 TI - Visible-light-mediated addition of alpha-aminoalkyl radicals generated from alpha silylamines to alpha,beta-unsaturated carbonyl compounds. AB - Visible-light-mediated addition of alpha-aminoalkyl radicals generated from alpha silylamines to alpha,beta-unsaturated carbonyl compounds using a photoredox catalyst is developed. We also succeeded in the isolation of a silyl enol ether as a primary product of the photochemical reaction. PMID- 22669614 TI - Positive roles for negative regulators in the mating response of yeast. AB - All cells must detect and respond to changes in their environment, often through changes in gene expression. The yeast pheromone pathway has been extensively characterized, and is an ideal system for studying transcriptional regulation. Here we combine computational and experimental approaches to study transcriptional regulation mediated by Ste12, the key transcription factor in the pheromone response. Our mathematical model is able to explain multiple counterintuitive experimental results and led to several novel findings. First, we found that the transcriptional repressors Dig1 and Dig2 positively affect transcription by stabilizing Ste12. This stabilization through protein-protein interactions creates a large pool of Ste12 that is rapidly activated following pheromone stimulation. Second, we found that protein degradation follows saturating kinetics, explaining the long half-life of Ste12 in mutants expressing elevated amounts of Ste12. Finally, our model reveals a novel mechanism for robust perfect adaptation through protein-protein interactions that enhance complex stability. This mechanism allows the transcriptional response to act on a shorter time scale than upstream pathway activity. PMID- 22669615 TI - A genomic bias for genotype-environment interactions in C. elegans. AB - The phenotype of an organism is determined by its genotype and environment. An interaction between these two arises from the differential effect of the environment on gene expression in distinct genotypes; however, the genomic properties identifying these are not well understood. Here we analyze the transcriptomes of five C. elegans strains (genotype) cultivated in five growth conditions (environment), and find that highly regulated genes, as distinguished by intergenic lengths, motif concentration, and expression levels, are particularly biased toward genotype-environment interactions. Sequencing these strains, we find that genes with expression variation across genotypes are enriched for promoter single-nucleotide polymorphisms (SNPs), as expected. However, genes with genotype-environment interactions do not significantly differ from background in terms of their promoter SNPs. Collectively, these results indicate that the highly regulated nature of particular genes predispose them for exhibiting genotype-environment interaction as a consequence of changes to upstream regulators. This observation may provide a deeper understanding into the origin of the extraordinary gene expression diversity present in even closely related species. PMID- 22669619 TI - Hydrogen sulfide: in the aftermath of argininosuccinate lyase and nitric oxide deficiency. PMID- 22669616 TI - Vascular density and endothelial cell expression of integrin alpha v beta 3 and E selectin in murine tumours. AB - The endothelial cell adhesion molecules, including the integrin alpha v beta 3 (alphavbeta3) and E-selectin, are involved in the process of angiogenesis required for tumour growth, cell migration and metastasis. The purpose of this study was to assess and compare widely used tumour models to select the ones most suitable for angiogenesis research. Fifteen murine tumours were selected including melanoma (B16), colon (C26, C38, C51), mammary (MA13, MA16, MA16/Adr, MA17, MA17/Adr, MA25, MA44), pancreatic (PO2, PO3), Glasgow osteogenic sarcoma (GOS) and Lewis lung carcinoma (LLC). The tumour vascular density, assessed using the platelet endothelial cell adhesion molecule 1 (PECAM-1; CD31) immunostaining, revealed that B16 melanoma was poorly vascularized (<5 %), whereas the colon and mammary tumours were well vascularized (5-15 %). The most vascularized tumours (>15 %) were the pancreatic tumours (PO2 and PO3), the sarcoma (GOS) and the lung tumour (LLC). The integrin alphavbeta3 and E-selectin, evaluated by immunohistology, showed that 7/15 tumours expressed the alphavbeta3 integrin which was homogeneously distributed on all tumour sections (B16, C26, MA17/Adr, MA25, MA44, PO2, LLC). E-selectin was expressed in 4/15 tumours and its expression was restricted to the tumour periphery. Only 2/15 tumours (B16 and C26) were shown to express both integrin alphavbeta3 and E-selectin. In conclusion, these data not only contribute to a better understanding of the tumour biology of murine tumours but can also guide the choice of appropriate models for antiangiogenic therapy, for selective drug delivery to tumours and the validation of tumour imaging modalities targeting these endothelial cell adhesion molecules. PMID- 22669623 TI - Low HPV vaccine coverage among female community college students. AB - This study assessed HPV vaccination and its correlates among culturally diverse 18-26 year-old community college women in Los Angeles. Specific research questions were: (1) What proportion of respondents have initiated the HPV vaccine, and what proportion have completed the three-dose series? (2) What demographic (e.g., age, ethnicity), psychosocial (e.g., vaccine-related beliefs, perceived social norms), and health care-related variables (e.g., health insurance status, provider recommendation, health care trust and satisfaction) are associated with vaccine initiation for this sample? Participants were recruited from the campus of a community college in central Los Angeles. All female students between 18 and 26 were eligible to participate. An anonymous web based survey assessed number of HPV vaccine doses received as well as demographic information, HPV- and HPV vaccine-related knowledge, attitudes, and behavior, perceived social norms, provider & health care system factors, sexual behavior, cervical health, and mother-daughter communication about sex. Analyses were conducted using 178 surveys. Multivariate logistic regression tested the relationships of statistically significant bivariate predictors to vaccine initiation. Those who initiated the vaccine were younger, more often had a health related academic major, thought the vaccine to be safer, perceived HPV severity lower, and perceived higher social approval for HPV vaccination than those unvaccinated. All who had initiated the vaccine had a doctor's recommendation. To increase uptake among 18-26-year-old women, research should explore provider interventions to increase vaccine recommendation, and also identify individuals and groups who may have negative beliefs about vaccine safety and efficacy to provide support in vaccine decision-making. PMID- 22669624 TI - Inflammatory myofibroblastic tumor of the lung: a benign lesion with aggressive behavior. AB - Inflammatory myofibroblastic tumor is a rare solid tumor that most often affects children and young adults. They present as myofibroblastic cell proliferations accompanied by inflammatory cells made up mostly of plasma cells. Although benign, the tumor may be very aggressive locally. In this report we describe a 22 year-old woman with primary invasive myofibroblastic tumor of the left lower lobe leading to a left pneumonectomy. PMID- 22669625 TI - New treatments of pancreatic neuroendocrine tumors: why using them? How to use them? PMID- 22669626 TI - Lactobacillus paracasei and Lactobacillus plantarum strains downregulate proinflammatory genes in an ex vivo system of cultured human colonic mucosa. AB - Significant health benefits have been demonstrated for certain probiotic strains through intervention studies; however, there is a shortage of experimental evidence relative to the mechanisms of action. Here, noninvasive experimental procedure based on a colon organ culture system has been used that, in contrast to most experimental in vitro models reported, can preserve natural immunohistochemical features of the human mucosa. This system has been used to test whether commensal lactobacilli (Lactobacillus paracasei BL23, Lactobacillus plantarum 299v and L. plantarum 299v (A(-))) were able to hinder inflammation like signals induced by phorbol 12-myristate 13-acetate (PMA)/ionomycin (IO). Whole genome microarrays have been applied to analyze expression differences, from which mRNA markers could be inferred to monitor the effect of putative probiotic strains under such conditions. Regarding the gene expression, PMA/IO treatment induced not only interleukin (IL)-2 and interferon gamma (IFN-gamma), as expected, but also other relevant genes related to immune response and inflammation, such as IL-17A, chemokine (C-X-C motif) ligand (CXCL) 9 and CXCL11. The ex vivo culturing did not modify the pattern of expression of those genes or others related to inflammation. Interestingly, this study demonstrated that lactobacilli downregulated those genes and triggered a global change of the transcriptional profile that indicated a clear homeostasis restoring effect and a decrease in signals produced by activated T cells. PMID- 22669628 TI - Escherichia coli: great diversity around a common core. AB - Escherichia coli outbreak in Germany, which resulted in more than 4,000 cases, including 908 cases of hemolytic-uremic syndrome (HUS) and at least 50 deaths, highlighted the genome plasticity of E. coli and the potential for new virulent strains to emerge. The analysis of 170 E. coli genome sequences for the presence of nine previously identified protective extraintestinal pathogenic E. coli antigens suggested the feasibility of a combination vaccine as a universal intervention against all pathogenic E. coli strains. IMPORTANCE: This article reports on the feasibility of a combination vaccine as a universal intervention against all pathogenic Escherichia coli strains. PMID- 22669627 TI - Polymorphisms in LEP and NPY genes modify the response to soluble fibre Plantago ovata husk intake on cardiovascular risk biomarkers. AB - The satiating effect of fibre consumption has been related to gut hormones, such as peptide YY and leptin. These peptides may also influence cardiovascular (CVD) risk biomarkers. Nevertheless, there is wide interindividual variation in metabolic responses to fibre consumption. The objective was to investigate differences in the effects of soluble fibre, in the form of Plantago ovata husk (Po-husk) treatment, on CVD risk biomarkers according to selected polymorphisms in genes related to satiety. The study was a multi-centred, double-blind, placebo controlled, parallel and randomised trial in mild-moderate hypercholesterolaemic patients (age range: 43-67 years). Eight polymorphisms in three genes related to satiety (LEP, NPY and PYY) were identified in 178 participants; 88 patients in the placebo (microcrystalline cellulose 14 g/day) group and 90 in the Po-husk (14 g/day) group, which had added to a low-saturated-fat diet for 8 weeks. The CVD biomarkers measured included the following: lipid profile, blood pressure (BP), glucose, insulin, hs-CRP, oxidised LDL and IL-6. Relative to the placebo, Po-husk consumption lowered the plasma total cholesterol concentration by 3.3 % according to rs7799039 polymorphism in the LEP gene (p < 0.05). Furthermore, the Po-husk reduced systolic BP (mean [95 % CI]) by -8 mmHg (-14.16; -1.90) and hs-CRP by 24.9 % in subjects with the AA genotype of the rs16147 polymorphism in the NPY gene (32 % of our total population; p < 0.05), which remained significant after Bonferroni correction. In conclusion, polymorphisms in the LEP and NPY genes potentiate the response to Po-husk, particularly the effects on systolic BP and the hs-CRP plasma concentration. PMID- 22669629 TI - Adaptation of human parainfluenza virus to airway epithelium reveals fusion properties required for growth in host tissue. AB - Paramyxoviruses, a family of RNA enveloped viruses that includes human parainfluenza virus type 3 (HPIV3), cause the majority of childhood croup, bronchiolitis, and pneumonia worldwide. Infection starts with host cell receptor binding and fusion of the viral envelope with the cell membrane at the cell surface. The fusion process requires interaction of the two viral surface glycoproteins, the hemagglutinin-neuraminidase (HN) and the fusion protein (F). We have previously shown that viruses with an HN/F pair that is highly fusogenic in monolayers of immortalized cells due to mutations in HN's secondary sialic acid binding site are growth impaired in differentiated human airway epithelium (HAE) cultures and in vivo. Here we have shown that adaptation of HPIV3 to growth in the lung is determined by specific features of HN and F that are different from those required for growth in cultured immortalized cells. An HPIV3 virus bearing a mutated HN (H552Q), which is fit and fusogenic in immortalized cells but unfit for growth in the lung, evolved into a less-fusogenic but viable virus in differentiated human airway epithelium. Stepwise evolution led to a progressive decrease in efficiency of fusion activation by the HN/F pair, with a mutation in F first decreasing the activation of F by HN and a mutation in HN's secondary sialic acid binding site decreasing fusion activation further and producing a stable virus. Adaptation of HPIV3 to successful growth in HAE is determined by specific features of HN and F that lead to a less easily activated fusion mechanism. IMPORTANCE: Human parainfluenza viruses (HPIVs) are paramyxoviruses that cause the majority of childhood cases of croup, bronchiolitis, and pneumonia worldwide, but there are currently no vaccines or antivirals available for treatment. Enveloped viruses must fuse their membrane with the target cell membrane in order to initiate infection. Parainfluenza virus fusion proceeds via a multistep reaction orchestrated by the two glycoproteins that make up its fusion machine. The receptor-binding hemagglutinin-neuraminidase (HN), upon receptor engagement, activates the fusion protein (F) to penetrate the target cell and mediate viral entry. In this study, we show that the precise balance of fusion activation properties of these two glycoproteins during entry is key for infection. In clinically relevant tissues, viruses evolve to acquire a set of fusion features that provide key clues about requirements for infection in human beings. PMID- 22669630 TI - Astrocyte-neuron communication: functional consequences. AB - Astrocyte-neuron communication has recently been proposed as a potential mechanism participating to synaptic transmission. With the development of this concept and accumulating evidences in favor of a modulation of synaptic transmission by astrocytes, has emerged the term gliotransmission. It refers to the capacity of astrocytes to release various transmitters, such as ATP, glutamate, D-serine, and GABA in the vicinity of synapses. While the cellular mechanisms involved in gliotransmission still need to be better described and, for some, identified, the aim of more and more studies is to determine the role of astrocytes from a functional point of view. This review will summarize the principal studies that have investigated a potential role of astrocytes in the various functions regulated by the brain (sleep, breathing, perception, learning and memory...). This will allow us to highlight the similarities and discrepancies in the signaling pathways involved in the different areas of the brain related to these functions. PMID- 22669632 TI - Study and reengineering of the binding sites and allosteric regulation of biosynthetic threonine deaminase by isoleucine and valine in Escherichia coli. AB - Biosynthetic threonine deaminase (TD) is a key enzyme for the synthesis of isoleucine which is allosterically inhibited and activated by Ile and Val, respectively. The binding sites of Ile and Val and the mechanism of their regulations in TD are not clear, but essential for a rational design of efficient productive strain(s) for Ile and related amino acids. In this study, structure based computational approach and site-directed mutagenesis were combined to identify the potential binding sites of Ile and Val in Escherichia coli TD. Our results demonstrated that each regulatory domain of the TD monomer possesses two nonequivalent effector-binding sites. The residues R362, E442, G445, A446, Y369, I460, and S461 only interact with Ile while E347, G350, and F352 are involved not only in the Ile binding but also in the Val binding. By further considering enzyme kinetic data, we propose a concentration-dependent mechanism of the allosteric regulation of TD by Ile and Val. For the construction of Ile overproducing strain, a novel TD mutant with double mutation of F352A/R362F was also created, which showed both higher activity and much stronger resistance to Ile inhibition comparing to those of wild-type enzyme. Overexpression of this mutant TD in E. coli JW3591 significantly increased the production of ketobutyrate and Ile in comparison to the reference strains overexpressing wild type TD or the catabolic threonine deaminase (TdcB). This work builds a solid basis for the reengineering of TD and related microorganisms for Ile production. PMID- 22669633 TI - Laboratory metabolic evolution improves acetate tolerance and growth on acetate of ethanologenic Escherichia coli under non-aerated conditions in glucose-mineral medium. AB - In this work, Escherichia coli MG1655 was engineered to produce ethanol and evolved in a laboratory process to obtain an acetate tolerant strain called MS04 (E. coli MG1655: DeltapflB, DeltaadhE, DeltafrdA, DeltaxylFGH, DeltaldhA, PpflB::pdc ( Zm ) -adhB ( Zm ), evolved). The growth and ethanol production kinetics of strain MS04 were determined in mineral medium, mainly under non aerated conditions, supplemented with glucose in the presence of different concentrations of sodium acetate at pH 7.0 and at different values of acid pH and a constant concentration of sodium acetate (2 g/l). Results revealed an increase in the specific growth rate, cell mass formation, and ethanol volumetric productivity at moderate concentrations of sodium acetate (2-10 g/l), in addition to a high tolerance to acetate because it was able to grow and produce a high yield of ethanol in the presence of up to 40 g/l of sodium acetate. Genomic analysis of the DeltapflB evolved strain identified that a chromosomal deletion of 27.3 kb generates the improved growth and acetate tolerance in MG1655 DeltapflB derivative strains. This deletion comprises genes related to the respiration of nitrate, repair of alkylated DNA and synthesis of the ompC gene coding for porin C, cytochromes C, thiamine, and colonic acid. Strain MS04 is advantageous for the production of ethanol from hemicellulosic hydrolysates that contain acetate. PMID- 22669631 TI - Role of human cytomegalovirus genotype polymorphisms in AIDS patients with cytomegalovirus retinitis. AB - Although several host factors have been identified to influence the course of HCMV infection, it still remains unclear why in AIDS patients without highly active antiretroviral therapy human cytomegalovirus (HCMV) retinitis is one of the most common opportunistic infections, whereas in other immunosuppressed individuals it has a low incidence. It was suggested that HCMV glycoprotein B strains may be suitable as marker for virulence and HCMV retinitis. Moreover, UL144 ORF, a member of the TNF-alpha receptor superfamily, may play a crucial role in innate defences and adaptive immune response of HCMV infection. Furthermore, sequence analyses of HCMV genes UL128, UL130, and UL131A as major determinants of virus entry and replication in epithelial and other cell types were performed. To evaluate the association of sequence variability of depicted viral genes with HCMV retinitis and in vitro growth properties in retinal pigment epithelial cells (RPE) and human foreskin fibroblasts (HFF), we compared 14 HCMV isolates obtained from vitreous fluid and urine of AIDS patients with clinically proven HCMV retinitis. Isolates were analyzed by PCR cycle sequencing and phylogenetic analysis. In addition, sequences of HCMV strains AF1, U8, U11, VR1814, and its cell culture adapted derivates were included. Sequence analysis of gB yielded three genetic subtypes (gB type 1 (5 isolates), gB type 2 (12 isolates), and gB type 3 (5 Isolates)), whereas sequence analysis of UL144 showed a greater diversity (7 isolates type 1A, 2 isolates type 1C, 7 isolates type 2, and 3 isolates type 3). In contrast, the UL128, UL130, and UL131A genes of all low-passage isolates were highly conserved and showed no preferential clustering. Moreover, in HFF and RPE cells, all of our HCMV isolates replicated efficiently independently of their genetic subtype. In conclusion, beside a possible link between the gB subtype 2 and HCMV retinitis, our study found no direct evidence for a connection between UL144/UL128/UL130/UL131A genotypes and the incidence of HCMV retinitis in AIDS patients. PMID- 22669635 TI - Surviving in the presence of sulphur dioxide: strategies developed by wine yeasts. AB - Sulphur dioxide has been used as a common preservative in wine since at least the nineteenth century. Its use has even become essential to the making of quality wines because of its antioxidant, antioxidasic and antiseptic properties. The chemistry of SO2 in wine is fairly complex due to its dissociation into different species and its binding to other compounds produced by yeasts and bacteria during fermentation. The only antiseptic species is the minute part remaining as molecular SO2. The latter concentration is both dependent on pH and concentration of free bisulphite. However, certain yeast species have developed cellular and molecular mechanisms as a response to SO2 exposure. Some of these mechanisms are fairly complex and have only been investigated recently, at least for the molecular mechanisms. They include sulphite reduction, sulphite oxidation, acetaldehyde production, sulphite efflux and the entry into viable but not culturable state, as the ultimate response. In this review, the chemistry of SO2 in wine is explained together with the impact of SO2 on yeast cells. The different defence mechanisms are described and discussed, mostly based on current knowledge available for Saccharomyces cerevisiae. PMID- 22669634 TI - Non-invasive determination of conjugative transfer of plasmids bearing antibiotic resistance genes in biofilm-bound bacteria: effects of substrate loading and antibiotic selection. AB - Biofilms cause much of all human microbial infections. Attempts to eradicate biofilm-based infections rely on disinfectants and antibiotics. Unfortunately, biofilm bacteria are significantly less responsive to antibiotic stressors than their planktonic counterparts. Sublethal doses of antibiotics can actually enhance biofilm formation. Here, we have developed a non-invasive microscopic image analyses to quantify plasmid conjugation within a developing biofilm. Corroborating destructive samples were analyzed by a cultivation-independent flow cytometry analysis and a selective plate count method to cultivate transconjugants. Increases in substrate loading altered biofilm 3-D architecture and subsequently affected the frequency of plasmid conjugation (decreases at least two times) in the absence of any antibiotic selective pressure. More importantly, donor populations in biofilms exposed to a sublethal dose of kanamycin exhibited enhanced transfer efficiency of plasmids containing the kanamycin resistance gene, up to tenfold. However, when stressed with a different antibiotic, imipenem, transfer of plasmids containing the kan(R+) gene was not enhanced. These preliminary results suggest biofilm bacteria "sense" antibiotics to which they are resistant, which enhances the spread of that resistance. Confocal scanning microscopy coupled with our non-invasive image analysis was able to estimate plasmid conjugative transfer efficiency either averaged over the entire biofilm landscape or locally with individual biofilm clusters. PMID- 22669636 TI - Diversity and antibiotic resistance of Acinetobacter spp. in water from the source to the tap. AB - Acinetobacter spp. are ubiquitous bacteria in the environment. Acinetobacter spp. isolated from a municipal drinking water treatment plant and from connected tap water were identified to the species level on the basis of rpoB gene partial sequence analysis. Intraspecies variation was assessed based on the analysis of partial sequences of housekeeping genes (rpoB, gyrB, and recA). Antibiotic resistance was characterized using the disk diffusion method and isolates were classified as wild or non-wild type (non-WT), according to the observed phenotype. The strains of Acinetobacter spp. were related to 11 different validly published species, although three groups of isolates, presenting low rpoB sequence similarities with previously described species, may represent new species. Most of the isolates were related to the species A. johnsonii and A. lwoffii. These two groups, as well as others related to the species A. parvus and A. tjernbergiae, were detected in the water treatment plant and in tap water. Other strains, related to the species A. pittii and A. beijerinckii, were isolated only from tap water. Most of the isolates (80 %) demonstrated wild type (WT) to all of the 12 antibiotics tested. Non-WT for tetracycline, meropenem, and ceftazidime, among others, were observed in water treatment plant or in tap water samples. Although, in general, this study suggests a low prevalence of acquired antibiotic resistance in water Acinetobacter spp., the potential of some species to acquire and disseminate resistance via drinking water is suggested. PMID- 22669637 TI - Reduced cardiac output and its correlation with coronary blood flow and troponin in asphyxiated infants treated with therapeutic hypothermia. AB - Perinatal asphyxia can lead to multi-organ insult which includes cardiovascular dysfunction. The objective was to study the relationship between cardiac function, perfusion and troponin. Unit database was accessed to identify infants with perinatal asphyxia over the last 2 years. Information from medical records and archived echocardiographic images was retrieved. Comparisons for echocardiographic information were made with healthy term infants. Seventeen infants with perinatal asphyxia were identified, of which three were excluded (one-33 weeks gestation, two-coagulopathy and pulmonary hypertension); 14 infants received therapeutic hypothermia. Median (range) gestation and birthweight were 39 (37-42) weeks and 3,550 (2,380-3,992) g respectively. Mean (S.D.) rectal temperature and time of echocardiogram were 33.5 +/- 0.5 degrees C and median (range) 7.7 h [3-10] respectively. Majority of infants had low biventricular outputs. Median (range) SVC flow was 29.8 ml/kg/min (13-96.2). Median (range) troponin was 0.77 MUg/L (0.17-2.6); normal <= 0.08 MUg/L. Markedly low coronary flows (diastolic VTI median (range) 2.1 (1.3-2.9) cm were noted compared to controls. Coronary flow had a significantly positive correlation with left ventricular output. Higher troponin levels were associated with lower aortic stroke velocity. A close association between cardiac output, perfusion and troponin was noted. A dichotomy between blood pressure and flow parameters was noted, indicating the wide variation in vascular resistance in these infants. Biventricular output, coronary and SVC flows were significantly higher in the control population. In conclusion, inter-variable relationship between cardiac output, coronary flow and troponin is an important addition to the understanding of cardiovascular impact of perinatal asphyxia. PMID- 22669638 TI - Sex and drug risk behavior pre- and post-emigration among Latino migrant men in post-Hurricane Katrina New Orleans. AB - High rates of sex and drug risk behaviors have been documented among Latino migrant men in the US. Whether these behaviors were established in the migrants' home countries or were adopted in the US has not been described and has implications for prevention strategies. Quarterly surveys were conducted to gather information on selected sex and drug risk practices of Latino migrant men who arrived in New Orleans after Hurricane Katrina seeking work. Both kappa scores and McNemar's tests were performed to determine if practice of these behaviors in home country was similar to practice post-emigration to the US. Female sex worker (FSW) patronage, same sex encounters (MSM), and crack cocaine use was more likely to occur post- rather than pre-emigration. Of those who ever engaged in these selected behaviors, most adopted the behavior in the US (i.e., 75.8% of FSW patrons, 72.7% of MSM participants, and 85.7% of crack cocaine users), with the exception of binge drinking (26.8%). Men who were living with a family member were less likely to adopt FSW patronage OR = 0.27, CI = 0.10-0.76, whereas men who earned >$465 per week were more likely to adopt crack cocaine use OR = 6.29 CI = 1.29, 30.57. Interventions that facilitate the maintenance of family cohesion and provide strategies for financial management may be useful for reducing sex and drug risk among newly arrived migrants. PMID- 22669640 TI - Percutaneous intradiscal high-pressure injection of saline and lidocaine in patients with lumbar intervertebral disc extrusion. AB - The intradiscal high-pressure injection of saline and lidocaine (IDHP) is a minimally invasive percutaneous procedure for a lumbar intervertebral disc extrusion. The purpose of this study was to investigate the clinical outcomes of IDHP in terms of pain relief, reduction of disability, and risk of complications. Thirty patients with primarily radicular pain due to an extrusion-type disc herniation who underwent IDHP were enrolled in the study. A visual analogue pain scale (VAS) and the Japanese Orthopedic Association (JOA) scoring system for the treatment of low back disorders were used at pre-treatment, 2 weeks post treatment, and 3 months post-treatment. The mean VAS decreased significantly (p < 0.01) from 64.3 mm at pre-treatment to 26.3 mm at 2 weeks post-treatment and 15.5 at 3 months post-treatment. The mean JOA score improved significantly (p < 0.01) from 14.7 to 21.3 at 2 weeks post-treatment and 24.6 at 3 months post-treatment. IDHP appeared to produce significant effects in patients with radicular pain, leading to the improvement of VAS and JOA scores. IDHP appears to be a safe, minimally invasive treatment option for a lumbar intervertebral disc extrusion. PMID- 22669639 TI - Factors influencing prostate cancer healthcare practices in Barbados, West Indies. AB - Although some investigations have assessed the barriers to prostate cancer screening among African-American men, limited data are available regarding such practices in similar African-origin populations. Key informant interviews were employed to obtain a range of perspectives pertaining to the healthcare practices of African-Barbadian men and to identify factors that obstruct prostate cancer screening in Barbados, West Indies. Gender-related perceptions were identified as a major obstruction to prostate cancer screening. Additionally, concerns about privacy, taking time away from work and mistrust of the medical community were reported as themes impeding the healthcare-seeking behaviors of African-Barbadian men. System-level barriers included limitations in access to care and ineffective dissemination of health information. Findings from this study suggest that targeted efforts aimed at modifying socio-cultural perceptions may assist in improving prostate cancer screening and general healthcare-seeking practices of African-Barbadian men and others who share similar beliefs. PMID- 22669641 TI - Bimodal distribution of risk for childhood obesity in urban Baja California, Mexico. AB - In Mexico, higher socioeconomic status (SES) has been found to be associated with increased risk for obesity in children. Within developed urban areas, however, there may be increased risk among lower SES children. Students in grades 4-6 from five public schools in Tijuana and Tecate, Mexico, were interviewed and weight, height and waist circumference (WC) measurements were taken. Interviews consisted of questions on food frequency, food insecurity, acculturation, physical activity and lifestyle practices. Multivariate logistic models were used to assess risk factors for obesity (having a body mass index [BMI] >=95th percentile) and abdominal obesity (a WC >90th percentile) using Stata 11.0. Five hundred and ninety students were enrolled; 43.7% were overweight or obese, and 24.3% were obese and 20.2% had abdominal obesity. Independent risk factors for obesity included watching TV in English (odds ratio [OR] 1.60, 95% confidence interval [CI] 1.06-2.41) and perceived child food insecurity (OR 1.57, 95% CI 1.05-2.36). Decreased risk for obesity was associated with female sex (OR 0.64, 95% CI 0.43 0.96), as was regular multivitamin use (OR 0.63, 95% CI 0.42-0.94). Risk obesity was also decreased with increased taco consumption (>=1*/week; OR 0.64, 95% CI 0.43-0.96). Independent risk factors for abdominal obesity included playing video games >=1*/week (OR 1.18, 95% CI 1.11-2.96) and older age group (10-11 years, OR 2.47, 95% CI 1.29-4.73 and >=12 years, OR 2.21, 95% CI 1.09-4.49). Increased consumption of tacos was also associated with decreased risk for abdominal obesity (>=1*/week; OR 0.56, 95% CI 0.40-1.00). We found a bimodal distribution for risk of obesity and abdominal obesity in school aged children on the Mexican border with the United States. Increased risk for obesity and abdominal obesity were associated with factors indicative of lower and higher SES including watching TV in English, increased video game playing and perceived food insecurity. Increased consumption of tacos (>=1*/week) was associated with decreased risk, possibly suggesting an association with children from middle income families. Regular multivitamin use was protective and future studies may focus on micronutrient supplementation as a means to prevent obesity in children or further investigate factors associated with vitamin use. Additionally, future studies need to examine the processes of acculturation on both sides of the US Mexican border that contribute to increased risk for obesity in children in relation to SES. PMID- 22669643 TI - Interpreting the empirical evidence on illegal gun market dynamics. AB - Thousands of Americans are killed by gunfire each year, and hundreds of thousands more are injured or threatened with guns in robberies and assaults. The burden of gun violence in urban areas is particularly high. Critics suggest that the results of firearm trace data and gun trafficking investigation studies cannot be used to understand the illegal supply of guns to criminals and, therefore, that regulatory and enforcement efforts designed to disrupt illegal firearms markets are futile in addressing criminal access to firearms. In this paper, we present new data to address three key arguments used by skeptics to undermine research on illegal gun market dynamics. We find that criminals rely upon a diverse set of illegal diversion pathways to acquire guns, gun traffickers usually divert small numbers of guns, newer guns are diverted through close-to-retail diversions from legal firearms commerce, and that a diverse set of gun trafficking indicators are needed to identify and shut down gun trafficking pathways. PMID- 22669642 TI - The association between parental perception of neighborhood safety and asthma diagnosis in ethnic minority urban children. AB - Low-income populations, minorities, and children living in inner cities have high rates of asthma. Recent studies have emphasized the role of psychosocial stress in development of asthma. Residence in unsafe neighborhoods is one potential source of increased stress. The study objective was to examine the association between parental perception of neighborhood safety and asthma diagnosis among inner city, minority children. Cross-sectional data from a community-based study of 6-8-year-old New York City children were used. Asthma was defined as parental report of physician-diagnosed asthma and at least one asthma-related symptom. Parental perceptions of neighborhood safety were assessed with a questionnaire. Associations between perceived neighborhood safety and asthma were examined using chi-squared tests. Multivariate logistic regression analyses were then performed. Five hundred four children were included with 79% female, 26.5% non-Hispanic Black, and 73.5% Hispanic. Asthma was present in 23.8% of children. There was an inverse association between feeling safe walking in the neighborhood and asthma with 45.7% of parents of asthmatic children reporting they felt safe compared to 60.9% of parents of non-asthmatic children (p = 0.006). Fewer parents of asthmatic children than of non-asthmatic children reported that their neighborhood was safe from crime (21.7% versus 33.9%, p = 0.018). In multivariate analyses adjusting for race/ethnicity, age, gender, socioeconomic status, number of smokers in the home and breastfeeding history, parents reporting feeling unsafe walking in the neighborhood were more likely to have a child diagnosed with asthma (OR = 1.89, 95%CI 1.13-3.14). Psychosocial stressors such as living in unsafe neighborhoods may be associated with asthma diagnosis in urban ethnic minority children. Addressing the increased asthma burden in certain communities may require interventions to decrease urban stressors. PMID- 22669644 TI - Health and safety strategies of urban taxi drivers. AB - This study describes health and safety concerns and self-care strategies of San Francisco taxi drivers. Focus groups and a written cross-sectional survey were done in a convenience sample of taxi drivers working in San Francisco. Sessions were audiotaped, transcribed in English, and independently coded to identify major health and safety themes, using thematic content analysis. Strategies to manage health and safety issues are the focus of this analysis. Five focus groups were held in 2009 with 36 participants. Major health and safety themes included stress, body pain, danger, vulnerable employment status, and concerns related to unhealthy working conditions. Self-care strategies included diffusion/decompression to manage stress, maintaining a positive attitude, maintaining power and control, and practicing proactive self-care. Creative self care strategies were described by taxi drivers to keep healthy and safe at work. These data will inform future self-care interventions to reduce health and safety risks of taxi driving. PMID- 22669645 TI - Food insufficiency, substance use, and sexual risks for HIV/AIDS in informal drinking establishments, Cape Town, South Africa. AB - HIV/AIDS is concentrated in impoverished communities. Two critical aspects of poverty are food insufficiency and substance abuse, and both are associated with sexual risks for HIV/AIDS in southern Africa. The current study is the first to examine both hunger and substance use in relation to sexual risks for HIV infection in South African alcohol serving establishments. Anonymous venue-based intercept surveys were completed by men (n = 388) and women (n = 407) patrons of six informal drinking places (e.g., shebeens) in Cape Town, South Africa. Food insufficiency and its more extreme form hunger were common in the sample, with 24 % of men and 53 % of women experiencing hunger in the previous 4 months. Multiple regression analyses showed that quantity of alcohol use was related to higher rates of unprotected sex for men and women. Trading sex to meet survival needs was related to food insufficiency and methamphetamine use among men but not women. Food insufficiency and substance use may both contribute to HIV risks in South African shebeens. However, the influence of hunger and substance use on sexual risks varies for men and women. Interventions to reduce HIV transmission risks may be bolstered by reducing both food insufficiency and substance use. PMID- 22669646 TI - Mitochondrial genomes gleaned from human whole-exome sequencing. PMID- 22669647 TI - Protease bias in absolute protein quantitation. PMID- 22669648 TI - Improved linear mixed models for genome-wide association studies. PMID- 22669650 TI - Shedding light on the BOLD fMRI response. PMID- 22669651 TI - Predicting microbial distributions in space and time. PMID- 22669652 TI - Rendering RNA in 3D. PMID- 22669655 TI - Developmental toxicology: methods and protocols. Volume overview: introduction. AB - The origins and history of the study of teratology and developmental toxicology span centuries of human experience. Anatomical malformations observed at birth have been described across many generations but the root causes of these events have been enigmatic and difficult to understand. Many factors may contribute to the lack of mechanistic understanding, but the miniscule size, inaccessibility, and the consequences of ethical concerns contribute heavily to the unique restrictions on developmental toxicology research. Classic teratogens, such as vitamin A, Rubella virus, thalidomide, and methyl mercury, have provided many insights into understanding the modes of chemical action that are responsible for causing defects but the specific mechanisms remain unclear. Developmental toxicology research has benefitted greatly in the past decades from discoveries made in related fields of study, including those from cancer research, stem cell biology, and developmental biology. New methods created and adapted for studies in developmental toxicology have taken on greater importance as gestational lesions can now be shown to have developmental and health consequences across the entire lifespan. PMID- 22669654 TI - Counting stem cells: methodological constraints. AB - The number of stem cells contributing to hematopoiesis has been a matter of debate. Many studies use retroviral tagging of stem cells to measure clonal contribution. Here we argue that methodological factors can impact such clonal analyses. Whereas early studies had low resolution, leading to underestimation, recent methods may result in an overestimation of stem-cell counts. We discuss how restriction enzyme choice, PCR bias, high-throughput sequencing depth and tagging method could affect the conclusions of clonal studies. PMID- 22669653 TI - Selected reaction monitoring-based proteomics: workflows, potential, pitfalls and future directions. AB - Selected reaction monitoring (SRM) is a targeted mass spectrometry technique that is emerging in the field of proteomics as a complement to untargeted shotgun methods. SRM is particularly useful when predetermined sets of proteins, such as those constituting cellular networks or sets of candidate biomarkers, need to be measured across multiple samples in a consistent, reproducible and quantitatively precise manner. Here we describe how SRM is applied in proteomics, review recent advances, present selected applications and provide a perspective on the future of this powerful technology. PMID- 22669656 TI - In vivo models of developmental toxicology. AB - The founding principles of teratology/developmental toxicology state that a developmental toxicants cause dysmorphogenesis when conceptuses are exposed at a sufficient dosage during a sensitive period of development in a sensitive species. While in vitro approaches in developmental toxicology can provide a means to assess the potency of toxicants, ultimately, the need to use whole animal models to demonstrate embryotoxicity is necessary to fully extrapolate findings to the human condition. This chapter is dedicated to reviewing the advantages of specific animal models and how these animal models may be used to assess toxicity in the embryo, both descriptively and mechanistically. PMID- 22669658 TI - Zebrafish embryo developmental toxicology assay. AB - A promising in vitro zebrafish developmental toxicology assay was generated to test compounds for their teratogenic potential. The assay's predictivity is approximately 87% in AB strain fish (Brannen KC et al., Birth Defects Res B Dev Reprod Toxicol 89:66-77, 2010). The procedure entails exposing dechorionated gastrulation-stage embryos to a range of compound concentrations for 5 days throughout embryonic and larva development. The larvae are evaluated for viability in order to identify an LC25 (the compound concentration in which 25% lethality is observed) and morphological anomalies using a numerical score system to identify the NOAEL (no observed adverse effect level). These values are used to calculate the teratogenic index (LC25/NOAEL ratio) of each compound. If the teratogenic index is equal to or greater than 10 then the compound is classified as a teratogen, and if the ratio is less than 10 then the compound is classified as a nonteratogen (Brannen KC et al., Birth Defects Res B Dev Reprod Toxicol 89:66-77, 2010). PMID- 22669657 TI - Caenorhabditis elegans as a model in developmental toxicology. AB - A number of practical advantages have made the nematode Caenorhabditis elegans a useful model for genetic and developmental biological research. These same advantages, along with conservation of disease and stress response pathways, availability of mutant and transgenic strains, and wealth of biological information, have led to the increased use of C. elegans in toxicological studies. Although the potential to study the mechanisms of developmental toxicology in C. elegans is promising, embryonic and larval growth tests to identify compounds that affect the nematode have remained the primary use of C. elegans in developmental toxicology. Here, we describe a C. elegans larval growth and development assay for medium- and high-throughput screening using the COPAS Biosort flow cytometer and provide descriptions of the data and subsequent analysis. PMID- 22669659 TI - Gene knockdown by morpholino-modified oligonucleotides in the zebrafish (Danio rerio) model: applications for developmental toxicology. AB - The zebrafish (Danio rerio) has long been used as a model for developmental biology, making it an excellent model to use also in developmental toxicology. The many advantages of zebrafish include their small size, prolific spawning, rapid development, and transparent embryos. They can be easily manipulated genetically through the use of transgenic technology and gene knockdown via morpholino-modified antisense oligonucleotides (MOs). Knocking down specific genes to assess their role in the response to toxicant exposure provides a way to further our knowledge of how developmental toxicants work on a molecular and mechanistic level while establishing a relationship between these molecular events and morphological, behavioral, and/or physiological effects (i.e., phenotypic anchoring). In this chapter, we address important considerations for using MOs to study developmental toxicology in zebrafish embryos and provide a protocol for their use. PMID- 22669660 TI - An amphibian model for studies of developmental reproductive toxicity. AB - The developmental programming of the reproductive system is vulnerable to chemical exposure. It is therefore important to evaluate long-term consequences of early life-stage exposure to endocrine disrupting chemicals. The African clawed frog Xenopus tropicalis has several characteristics which facilitates studies of developmental reproductive toxicity. Here, I present a X. tropicalis test protocol, including study design, exposure regime, and endpoints for chemical disruption of sex differentiation, reproductive organ development, the thyroxin-regulated metamorphosis, oestrogen synthesis (activity of the CYP19 aromatase enzyme), and fertility. PMID- 22669661 TI - Avian models in teratology and developmental toxicology. AB - The avian embryo is a long-standing model for developmental biology research. It also has proven utility for toxicology research both in ovo and in explant culture. Like mammals, avian embryos have an allantois and their developmental pathways are highly conserved with those of mammals, thus avian models have biomedical relevance. Fertile eggs are inexpensive and the embryo develops rapidly, allowing for high-throughput. The chick genome is sequenced and significant molecular resources are available for study, including the ability for genetic manipulation. The absence of a placenta permits the direct study of an agent's embryotoxic effects. Here, we present protocols for using avian embryos in toxicology research, including egg husbandry and hatch, toxicant delivery, and assessment of proliferation, apoptosis, and cardiac structure and function. PMID- 22669662 TI - Overview of in vitro models in developmental toxicology. AB - In vitro methods used to study the modes of action of developmental toxicants range in biological complexity from cell monocultures to the culture of intact viable conceptuses. Primitive methods were static in nature and generally failed to provide for the adequate transfer of oxygen and nutrients to the cells and tissues being cultured. Modern methods have improved on these deficits to allow growth of cells, tissues, and whole conceptuses at rates that mirror those seen in vivo. The experimental challenges encountered with in vitro studies are also not unlike those seen in vivo where scale, accessibility, and developmental timing continue to persist as significant challenges. In vitro models have advantages in the ability to control environmental conditions and the direct exposure to toxicants so that specific effects on cell growth, differentiation, and morphology can be assessed directly in cells that have retained a sufficient degree of pluripotency. In vitro methods range in biological complexity from primary and immortalized cell cultures, organ and tissue cultures, and whole embryo cultures using intact, viable conceptuses explanted from a variety of species. Different experimental approaches are used for the various stages of development and cover the spectrum from preimplantation, periimplantation, and on to postimplantation periods of development. PMID- 22669663 TI - Primary cell and micromass culture in assessing developmental toxicity. AB - Under the European Commission's New Chemical Policy both currently used and new chemicals should be tested for their toxicities in several areas, one of which was reproductive/developmental toxicity. Thousands of chemicals will need testing which will require a large number of laboratory animals. In vitro systems (as pre screens or as validated alternatives) appear to be useful tools to reduce the number of whole animals used or refine procedures and hence decrease the cost for the chemical industry. Validated in vitro systems exist for developmental toxicity/embryotoxicity testing. Indeed, three assays have recently been validated: the whole embryo culture (WEC), the rat limb bud micromass (MM), and the embryonic stem cell test (EST). In this article, the use of primary embryonic cell culture, and in particular micromass culture, including a relatively novel chick heart micromass (MM) culture system has been described and compared to the validated D3 mouse embryonic stem cell (ESC) test. PMID- 22669664 TI - Embryonic stem cell test: stem cell use in predicting developmental cardiotoxicity and osteotoxicity. AB - In order to prevent birth defects, toxicology programs have been designed to identify toxicities that may potentially be encountered in human embryos. With appropriate toxicity data sets, acceptable exposure levels and actual safety of prescription and nonprescription drugs as well as environmental chemicals could be established for individuals that are more vulnerable to chemical exposure, such as pregnant women and their unborn children. The gathering of such embryotoxicity data is currently performed in animal models. To reduce the spending of live animals, an assortment of in vitro assays has been proposed.In this chapter, the embryonic stem cell test (EST) is reviewed as an alternative model for testing embryotoxicity. In contrast to most in vitro toxicity assays, the EST uses two permanent cell lines: murine 3T3 fibroblasts and murine embryonic stem cells (ESCs). To establish developmental toxicity, the difference in sensitivity towards the cytotoxic potential of a given test compound between the adult and the embryonic cells is compared with an MTT assay. In addition, the EST contrasts the inhibition of development that a test compound may cause utilizing the in vitro differentiation potential of the ESCs.We describe here protocols to culture both cell lines as well as the differentiation of the ESCs into cardiomyocytes. Classically, the EST assesses developmental toxicity through counting of contracting cardiomyocyte agglomerates, which will be described as one endpoint. Although this classic EST has been validated in an EU-wide study, tremendous problems exist with the choice of endpoints, the EST's predictivity, and the associated costs. We therefore also give details on the more recently introduced molecular analysis of cardiomyocyte-specific mRNAs, which already has been used to successfully predict developmental toxicity. Moreover, this chapter will explain a method to evaluate developmental bone toxicity and hencewith an experimental setup to differentiate ESCs into osteoblasts is presented along with two endpoint analyses that will establish generation of osteoblasts as well as their calcification in culture. The various differentiation endpoints may be set into relation to the cytotoxicity that the same test compound causes to ultimately predict the potential of a compound to excite developmental toxicity in vivo. PMID- 22669665 TI - Mouse embryonic stem cell adherent cell differentiation and cytotoxicity assay. AB - There are thousands of environmental chemicals for which there is limited toxicological information, motivating the development and application of in vitro systems to profile the biological effects of xenobiotic exposure and predict their potential developmental hazard. An adherent cell differentiation and cytotoxicity (ACDC) assay was developed using pluripotent mouse embryonic stem cells (mESCs) to evaluate chemical-induced effects on both stem cell viability and differentiation. This assay uses an In-Cell Western technique after a 9-day culture. DRAQ5/Sapphire700 cell/DNA stains are used to quantify cell number and myosin heavy chain (MHC) protein is used as a marker of cardiomyocyte differentiation. MHC is corrected for cell number, thereby separating cytotoxicity and effects on differentiation. The ACDC assay can be used to evaluate the effects of xenobiotics on mESC differentiation and cell number in the same sample. PMID- 22669666 TI - The murine limb bud in culture as an in vitro teratogenicity test system. AB - There is widespread interest today in the use of in vitro methods to study normal and abnormal development. The limb is attractive in this context, since much is known about pattern formation during limb development. The murine limb bud culture technique described in this chapter was developed and refined in the 1970s. In this culture system, limb development mimics that in vivo, although the rate is slower. Growth and cartilage differentiation lead to the formation of proximal and distal structures with an "in vivo-like" 3D shape. Today, limb bud cultures are used to study the roles of genes during embryogenesis and the mechanisms by which chemicals interfere with critical signaling pathways. In this system, uniform developmental stages are selected for assessment, exposures are controlled precisely, and the confounding influences of maternal metabolism and transport are avoided. PMID- 22669667 TI - Rodent whole embryo culture. AB - The direct effects of chemical exposures, environmental extremes, and nutrient quality/quantity have been very difficult to study in mammalian embryos due to their anatomical inaccessibility, paucity of tissues, and other factors such as real ethical concerns in human studies. Many acute and chronic developmental anomalies can trace their origins to postimplantation phases of gestation where the organs are first being established and growth and differentiation are in highly active states of flux. Most agents and conditions that produce birth defects are believed to act during this period of organogenesis. The evolution of rodent whole embryo culture (WEC) techniques has provided a valuable experimental model where physiological conditions and exposures can be carefully controlled and manipulated to test hypotheses and explore biochemical and molecular mechanisms of action. Exposure to chemical agents can be controlled through their direct addition to the culture medium. Optimal in vitro culture conditions support the growth of intact, viable conceptuses (embryo and associated extraembryonic membranes) from early egg cylinder stages through establishment of the neural plate, gastrulation, neural tube closure, onset of active heartbeat and circulation, and the initial formation of all major organ systems that occur prior to the establishment of a functional placenta. Detailed comparisons of in vivo and in vitro growth show that conceptuses grown in WEC are nearly identical, structurally and functionally, to conceptuses of the same developmental stage that are allowed to develop normally in vivo. Culture conditions and mechanical apparatus can be modified to suit a large number of different experimental approaches and paradigms. PMID- 22669668 TI - Rabbit whole embryo culture. AB - Although the rabbit is used extensively in developmental toxicity testing, relatively little is known about the fundamental developmental biology of this species let alone mechanisms underlying developmental toxicity. This paucity of information about the rabbit is partly due to the historic lack of whole embryo culture (WEC) methods for the rabbit, which have only been made available fairly recently. In rabbit WEC, early somite stage embryos (gestation day 9) enclosed within an intact amnion and attached to the visceral yolk sac are dissected from maternal tissues and placed in culture for up to 48 h at approximately 37 degrees C and are continuously exposed to an humidified gas atmosphere mixture in a rotating culture system. During this 48 h culture period, major phases of organogenesis can be studied including cardiac looping and segmentation, neural tube closure, and development of anlagen of the otic system, eyes and craniofacial structures, somites and early phases of limb development (up to bud stage), as well as expansion and closure of the visceral yolk sac around the embryo. Following completion of the culture period, embryos are evaluated based on several growth and development parameters and also are assessed for morphological abnormalities. The ability to sustain embryo development independent of the maternal system allows for exposure at precise development stages providing the opportunity study the direct action of a teratogen or one of its metabolites on the developing embryo. Rabbit WEC is perhaps most useful when used in conjunction with rodent WEC methods to investigate species-specific mechanisms of developmental toxicity. PMID- 22669669 TI - Assessment of xenobiotic biotransformation including reactive oxygen species generation in the embryo using benzene as an example. AB - Quantification of embryonic metabolic capacity is an important tool in developmental toxicology research. Bioactivation of xenobiotics into reactive intermediates often contributes to embryo toxicity; thus, identification and quantification of these toxic metabolites is essential to gain further understanding of developmental toxicity. This chapter uses the environmental chemical benzene as a model xenobiotic to describe the detection of both metabolites and reactive oxygen species (ROS) in fetal liver. Briefly, mice are bred and the presence of a vaginal plug in a female mouse indicates gestational day 1. On the desired gestational day, pregnant dams are exposed to benzene followed by sacrifice at the desired time-point after exposure. Using gas chromatography coupled to mass spectrometry, the detection of benzene metabolites can be achieved. Additionally, we describe the measurement of ROS by flow cytometry using the fluorescent probe 5-(and-6)-chloromethyl-2',7' dichlorofluorescein diacetate, which readily diffuses into cells and, upon oxidation by any ROS, is converted to the highly fluorescent, negatively charged carboxydichlorofluorescein, which remains trapped within the cells. PMID- 22669670 TI - Methodological approaches to cytochrome P450 profiling in embryos. AB - Cytochrome P450 enzymes (CYPs) are heme thiolate proteins essential for vertebrate development and also play important roles in toxicology as well as normal metabolic function. CYP enzymes catalyze the oxidative biotransformation of many endogenous and exogenous chemicals, including steroids and eicosanoids, and drugs and other xenobiotic toxicants. Many CYPs have known for their potential roles in development, and many chemicals that cause developmental abnormalities are substrates for CYPs. The roles and regulation of most xenobiotic metabolizing CYPs during development are unknown, impeding understanding of mechanisms of developmental toxicity. The zebrafish (Danio rerio) has become one of the premier models in vertebrate developmental biology, in large part because of the logistical advantages of rapid external development, high adult maintenance density, and significant (bio)technological tool availability. The increasing use of zebrafish in drug discovery and mechanistic toxicology demands knowledge of CYP gene regulation and function. Here, we present methods to examine CYP expression during early development in zebrafish, with an emphasis on developmental microarrays. PMID- 22669671 TI - Analysis of Nrf2-mediated transcriptional induction of antioxidant response in early embryos. AB - Nrf2 is a transcription factor that regulates the induction of an expansive set of antioxidant proteins that act in synergy to remove reactive oxygen species (ROS). We have recently discovered that Nrf2 signaling is involved in the induction of antioxidant response in ethanol-exposed embryos. We have also demonstrated that chemically induced transcriptional activation of Nrf2 and subsequent induction of a broad spectrum of antioxidant proteins can act as an endogenous protective system against ethanol-induced oxidative stress and apoptosis in early mouse embryos. This chapter describes the methods used to analyze Nrf2-mediated transcriptional induction of antioxidant response in mouse embryos. Data which have been generated by using these methods have also been included to provide examples of their usefulness in evaluating Nrf2-mediated antioxidant response in early embryos. PMID- 22669672 TI - Regulation and control of AP-1 binding activity in embryotoxicity. AB - The electrophoretic mobility shift assay (EMSA) is a sensitive relatively straightforward methodology used to detect sequence-specific DNA-protein interactions. It is the fundamental procedure of several variants that allow qualitative and quantitative assessments of protein-nucleic acid complexes. Classically, nuclear proteins and DNA are combined and the resulting mixture is electrophoretically separated in polyacrylamide or agarose gel under native conditions. The distribution within the gel is generally detected with autoradiography of the 32P-labeled DNA. The underlying principle is that nucleic acid with protein bound to it will migrate more slowly through a gel matrix than the free nucleic acid. In this chapter, a representative protocol is described that addresses specific challenges of using whole embryos as the nuclear protein source, and the most common and informative EMSA variant, the "supershift," is also presented. The important points are underscored and approaches for troubleshooting are explained. References are provided for alternative methods and extensions of the basic protocol. PMID- 22669673 TI - Thioredoxin redox status assessment during embryonic development: the redox Western. AB - Oxidative stress can contribute significantly to the mechanisms that cause teratogenesis and embryotoxicity, but cellular antioxidant defense systems have evolved to counteract the detrimental consequences of oxidative insult. Numerous antioxidant systems exist in developing organisms but have been shown to be dynamically expressed and may only become functional during specific periods of development. Thioredoxins (Trxs) are a class of low-molecular-weight oxidoreductase antioxidants that play an important role in reactive oxygen species detoxification and transcription factor regulation, both of which are critical to normal development. In this chapter, we describe a method by which cytosolic thioredoxin-1 (Trx1) and mitochondrial thioredoxin-2 (Trx2) redox status can be measured. In brief, derivatization of reduced Trx at the active site cysteine thiols using a large maleimide derivative, targeting the redox sensitive residues making the protein larger. Nonreducing SDS-PAGE is performed to separate reduced (labeled) and oxidized (unlabeled) Trx based on their size. Band densitometries can be measured and used in the Nernst equation to calculate redox potentials. These approaches provide a means to evaluate this unique redox couple during development and allow for the measurement of compartmentalized (mitochondrial vs. cytosolic) oxidation during chemical insult. PMID- 22669674 TI - Methods for the determination of plasma or tissue glutathione levels. AB - We present two different methods for determining levels of glutathione in complex biological samples and plasma. The DTNB/GR enzyme recycling method is sensitive and requires no specialized equipment. The HPLC method is particularly useful for situations in which sample amounts are limited. Detailed instructions for performing each method as well as the advantages and disadvantages of each are discussed in this chapter. PMID- 22669675 TI - Oxidative stress, thiols, and redox profiles. AB - Oxidative stress has been recognized as a contributing factor in the toxicity of a large number of developmental toxicants. Traditional definitions of oxidative stress state that a shift in the balance between reduced and oxidized biomolecules within cells, in favor of the latter, result in changes that are deleterious to vital cell functions and can culminate in malformations and death. The glutathione (GSH)/glutathione disulfide (GSSG) redox couple has been the traditional marker of choice for characterization of oxidative stress because of its high concentrations and direct roles as antioxidant and cellular protectant. Steady state depletion of GSH through conjugation, oxidation, or export has often been reported as the sole criteria for invoking oxidative stress and a myriad of associated deleterious consequences. Numerous other, mostly qualitative, observations have also been reported to suggest oxidative stress has occurred but it is not always clear how well they reflect the state of a cell or its functions. Our emerging understanding of redox signaling and the roles of reactive oxygen species (ROS), thiols, oxidant molecules, and cellular antioxidants, all acting as second messengers, has prompted a redefinition of oxidative stress based on changes in the real posttranslational protein thiol modifications that are central to redox regulation and control. Thiol-based redox couples such as GSH/GSSG, cysteine/cystine (cys/cySS), thioredoxin reduced/thioredoxin-oxidized (TRX(red)/TRX(ox)) form independent signaling nodes that selectively regulate developmental events and are closely linked to changes in intracellular redox potentials. Accurate assessment of the consequences of increased free radicals in developing conceptuses should best be made using a battery of measurements including the quantitative assessment of intracellular redox potential, ROS, redox status of biomolecules, and induced changes in specific redox signaling nodes. Methods are presented for a determination of ROS production, soluble thiol oxidation, redox potential, and a proteomic approach to evaluate the thiol oxidation state of specific proteins. PMID- 22669676 TI - A review of toxicogenomic approaches in developmental toxicology. AB - Over the past decade, the use of gene expression profiling (i.e., toxicogenomics or transcriptomics) has been established as the vanguard "omics" technology to investigate exposure-induced molecular changes that underlie the development of disease. As this technology quickly advances, researchers are striving to keep pace in grasping the complexity of toxicogenomic response while at the same time determine its applicability for the field of developmental toxicology. Initial studies suggest toxicogenomics to be a promising tool for multiple types of study designs, including exposure-response investigations (dose and duration), chemical classification, and model comparisons. In this review, we examine the use of toxicogenomics in developmental toxicology, discussing biological and technical factors that influence response and interpretation. Additionally, we provide a framework to guide toxicogenomic investigations in the field of developmental toxicology. PMID- 22669677 TI - Epigenetic approaches and methods in developmental toxicology: role of HDAC inhibition in teratogenic events. AB - The relevance of histone acetylation/deacetylation in regulating decompaction/compaction of chromatin and, consequently, in regulating gene expression, has been described for many physiological and pathological biological processes, including normal and altered embryo development. Similarly to other biological systems, also in embryo cells the acetylation status is controlled by the antagonist activity of histone acetyl transferases (HATs) and histone deacetylases (HDACs) and is influenced by other factors acting on chromatin structure (i.e., every epigenetic modification of chromatin). The relevance of acetylation during development has been demonstrated in all developmental phases, from gametogenesis to zygote formation and during early and late embryonic stages. Moreover, the increase number of xenobiotic showing HDAC inhibitory activity recently focused the attention of teratologists on the possible role of HDAC inhibition as a novel teratogenic mechanism. This hypothesis has been demonstrated at least in embryos at somitogenic stages (for mouse embryos from stage E8 till stage E15): HDAC inhibition, histone hyperacetylation, increased cell death (apoptosis) has been suggested as the main event cascade involved in axial skeletal defects induced in rodent by a number of HDAC inhibitors, including the antiepileptic drug valproic acid. PMID- 22669679 TI - Assessment of histiotrophic nutrition using fluorescent probes. AB - Histiotrophic nutrition is a process whereby the rodent visceral yolk sac (VYS) internalizes exogenous macromolecules, degrades them, and sends the degradation products to the embryo for use in de novo macromolecular biosynthesis. This process is important for embryonic development during early gestation prior to the formation of the functional placenta. Quantification and visualization of histiotrophic nutrition can be accomplished using fluorescent tracer molecules such as fluorescein isothiocyanate-conjugated albumin (FITC-albumin) that can be visualized using fluorescent microscopy and quantified using fluorescent spectroscopy. The methods are simple and can provide complementary functional and structural information in studies of the effects of embryotoxicants on yolk sac function. PMID- 22669678 TI - DNA methylation screening and analysis. AB - DNA methylation is an epigenetic form of gene regulation that is universally important throughout the life course, especially during in utero and postnatal development. DNA methylation aids in cell cycle regulation and cellular differentiation processes. Previous studies have demonstrated that DNA methylation profiles may be altered by diet and the environment, and that these profiles are especially vulnerable during development. Thus, it is important to understand the role of DNA methylation in developmental governance and subsequent disease progression. A variety of molecular methods exist to assay for global, gene-specific, and epigenome-wide methylation. Here we describe these methods and discuss their relative strengths and limitations. PMID- 22669680 TI - Diabetic embryopathy. AB - Diabetic embryopathy reflects a scientific enigma--how does a seemingly rich intrauterine environment manage to disturb the development of the embryo? Which compounds in that environment may be teratogenic--and how shall we find them? How can we investigate a putative dose-response nature of the teratogen, i.e., how can we monitor the effects of varied severity of the diabetic state (which can be varied in a number of metabolic ways) on the embryonic development? Here, the whole embryo culture (WEC) technique provides an excellent tool for such studies. WEC is thus currently used to investigate the effect of graded levels of diabetes (e.g., hyperglycemia, hyperketonemia, increased branched chain amino acid (BCAA) levels), and putative antiteratogenic agents (antioxidants, folic acid, arachidonic acid, inositol), as well as the effect of different embryonic genotypes on diabetes-induced (mal)development. WEC is the only method, which is able to couple specific embryonic maldevelopment to precise changes in substrate levels or the (epi)genotype of the embryo. Using this method, we have been able to demonstrate that a diabetic environment--culture of embryos in serum from diabetic animals or in serum with increased levels of glucose, beta hydroxybutyrate or alpha-ketoisocaproic acid (KIC)--causes increased embryonic maldevelopment, and that this dysmorphogenesis is blocked by the addition of ROS scavenging agents to the culture medium. Genetically, others and we have demonstrated that Pax-3 downregulation predisposes for diabetes-induced dysmorphogenesis. PMID- 22669681 TI - Gene expression analysis in developing embryos: in situ hybridization. AB - In situ hybridization (ISH) is a technique that offers the ability to detect, and assay for alterations in, the spatial distribution of gene transcripts in an organism and is thus an invaluable tool to understanding the molecular basis during various developmental processes. Changes at the molecular levels consequent to toxicological perturbations and characterization of the expression of new or uncharacterized genes can be performed at the spatial and temporal levels with relative ease, speed, and specificity. Knowledge of expression pattern of specific genes allows one to formulate hypotheses of possible functions, molecular partners, and signaling pathways. We describe a procedure for ISH analysis of developing whole mouse embryos with the use of nonradioactive in vitro transcribed antisense RNA (riboprobes) and detected indirectly by a colorimetric reaction. PMID- 22669682 TI - Assessment of gross fetal malformations: the modernized Wilson technique and skeletal staining. AB - Teratology is the study of anatomical and physiological abnormalities, commonly known as birth defects. If an embryo is exposed to a harmful substance, or teratogen, during the critical period of development, an ensuing malformation may occur. These malformations and their associated mechanisms are studied and analyzed in laboratory animals in order to prevent them from occurring in humans. Rodents, such as rabbits, rats, and mice, have commonly been used in such studies because of their similarity to humans. In 1959, James G. Wilson designed, developed, and tested a protocol on how to observe and analyze structural malformations in rodent fetuses, which included external examination, skeletal evaluation, soft tissue analysis, and data collection/analysis. Although many years have passed since Wilson created this protocol, it is still widely used to this day, and only minor changes have been made to his instructions such as the chemicals used in the experiments and also the analysis of the experimental data. While only minor modifications have been made to this protocol since its beginning, major advances have been made in the dissemination of teratology information to the public such that information is now available through the Internet--information including the identification of an increasing number of teratogens and the understanding of the pathogenesis as it relates to the etiology of birth defects. Despite these advances, however, there has been little decrease in the overall incidence of major birth defects, although significantly improved reporting and ascertainment of birth defects must be factored into the equation in determining birth defect rates. Future birth defect prevention may be based on the understanding of individual genomes and pharmacogenomics, and as the interaction between teratogenic and genetic factors is better understood--with the hope that the incidence of both chemically induced and genetic defects will one day be substantially reduced. PMID- 22669683 TI - Diagnostic and therapeutic value of ductoscopy in nipple discharge and intraductal proliferations compared with standard methods. AB - BACKGROUND: Fiberoptic ductoscopy is a practical and direct approach that allows the visualization of intraductal breast disease. The aim of this study was to assess the efficacy of ductoscopy in the diagnosis and management of intraductal lesions. METHODS: Data on 357 ductoscopic investigations from patients with nipple discharge were collected prospectively. Seventy-five patients were diagnosed as having intraductal papillary lesions and these cases were evaluated by final histopathology (55 solitary, 14 multiple papillomatosis, 6 premalignant or malignant lesions). Results of classical diagnostic studies using ultrasonography, mammography, and galactography were compared with those of ductoscopy and pathology. RESULTS: The sensitivities of investigation methods for papillomas in this study were 72 % in ultrasonography, 62.9 % in mammography, 81.4 % in galactography, and 86.6 % in ductoscopy. With ductoscopic papillomectomy (DP), almost 30 % of patient with solitary papilloma did not require further extensive surgery. CONCLUSION: Since there is an increased risk of malignancy, surgical excision is recommended for multiple, larger papillomas and for papillomas with atypia and in addition for papillomas where diagnostic tools produce suspicious findings. On the other hand DP is a minimally invasive intervention and can aid in the follow-up of lesions proven to have no atypia. PMID- 22669685 TI - Deforestation and the limited contribution of forests to rural livelihoods in West Africa: evidence from Burkina Faso and Ghana. AB - Forest degradation in West Africa is generally thought to have negative consequences on rural livelihoods but there is little overview of its effects in the region because the importance of forests to rural livelihoods has never been adequately quantified. Based on data from 1014 rural households across Burkina Faso and Ghana this paper attempts to fill this knowledge gap. We demonstrate that agricultural lands and the non-forest environment including parklands are considerably more valuable to poor as well as more well-off rural households than forests. Furthermore, product types supplied by the non-forest environment are almost identical with those from forests. Accordingly, forest clearance/degradation is profitable for and, hence, probably performed by rural people at large. We attribute rural people's high reliance on non-forest versus forest resources to the two countries' restrictive and inequitable forest policies which must be reformed to promote effective forest conservation, e.g., to mitigate climate change. PMID- 22669684 TI - An 11-year analysis of the prevalent uropathogens and the changing pattern of Escherichia coli antibiotic resistance in 38,530 community urinary tract infections, Dublin 1999-2009. AB - BACKGROUND: Knowledge of local antimicrobial resistance patterns is essential for evidence-based empirical antibiotic prescribing, and a cutoff point of 20% has been suggested as the level of resistance at which an agent should no longer be used empirically. We sought to identify the changing incidence of causative uropathogens over an 11-year period. We also examined the trends in antibiotic resistance encountered in both the pooled urine samples and those where the causative organism was Escherichia coli. PATIENT AND METHODS: A retrospective analysis of the antimicrobial resistance within the positive community urine isolates over the 11-year period, 1999 to 2009, in a single Dublin teaching hospital was performed. RESULTS: In total 38,530 positive urine samples processed at our laboratory originated in the community of which 23,838 (56.7%) had E. coli as the infecting organism. The prevalence of E. coli has been increasing in recent years in community UTIs with 70.4% of UTIs in the community caused by E.coli in 2009. Ampicillin and trimethoprim were the least-active agents against E. coli with mean 11-year resistance rates of 60.8 and 31.5%, respectively. Significant trends of increasing resistance over the 11-year period were identified for trimethoprim, co-amoxyclav, cefuroxime and gentamicin. Ciprofloxacin remains a reasonable empirical antibiotic choice in this community with an 11-year resistance rate of 10.6%. Higher antibiotic resistance rates were identified in the male population and in children. CONCLUSION: Resistance rates to commonly prescribed antibiotics are increasing significantly. This data will enable evidence-based empirical prescribing which will ensure more effective treatment and lessen the emergence of resistant uropathogens in the community. PMID- 22669686 TI - Mercury levels in pristine and gold mining impacted aquatic ecosystems of Suriname, South America. AB - Mercury levels in sediment and predatory fish were measured for 53 localities in Suriname. The average mercury level in bottom sediment surpassed the Canadian standard for sediment in most localities, except the coastal plains. Of the predatory fish, 41 % had a mercury level above the European Union standard for human consumption of 0.5 MUg g(-1). Highest mercury levels were found in fish from the Brokopondo Reservoir and from the Upper Coppename River. High levels of mercury in fish in pristine areas are explained by atmospheric transportation of mercury with the northeastern trade winds followed by wet deposition. Contrary to gold mining areas, where mercury is bound to drifting sediments, in "pristine" areas the mercury is freely available for bio-accumulation and uptake. Impacts on piscivorous reptiles, birds, and mammals are unknown, but likely to be negative. PMID- 22669687 TI - Cyproterone synthesis, recognition and controlled release by molecularly imprinted nanoparticle. AB - In this study, we used novel synthetic conditions of precipitation polymerization to obtain nanosized cyproterone molecularly imprinted polymers for application in the design of new drug delivery systems. The scanning electron microscopy images and Brunauer-Emmett-Teller analysis showed that molecularly imprinted polymer (MIP) prepared by acetonitrile exhibited particles at the nanoscale with a high degree of monodispersity, specific surface area of 246 m(2) g(-1), and pore volume of 1.24 cm(3) g(-1). In addition, drug release, binding properties, and dynamic light scattering of molecularly imprinted polymers were studied. Selectivity of MIPs was evaluated by comparing several substances with similar molecular structures to that of cyproterone. Controlled release of cyproterone from nanoparticles was investigated through in vitro dissolution tests and by measuring the absorbance by HPLC-UV. The pH dissolution media employed in controlled release studies were 1.0 at 37 degrees C for 5 h and then at pH 6.8 using the pH change method. Results show that MIPs have a better ability to control the cyproterone release in a physiological medium compared to the non molecularly imprinted polymers (NMIPs). PMID- 22669688 TI - Soaking pretreatment of corn stover for bioethanol production followed by anaerobic digestion process. AB - The production of ethanol and methane from corn stover (CS) was investigated in a biorefinery process. Initially, a novel soaking pretreatment (NaOH and aqueous ammonia) for CS was developed to remove lignin, swell the biomass, and improve enzymatic digestibility. Based on the sugar yield during enzymatic hydrolysis, the optimal pretreatment conditions were 1 % NaOH+8 % NH(4)OH, 50 degrees C, 48 h, with a solid-to-liquid ratio 1:10. The results demonstrated that soaking pretreatment removed 63.6 % lignin while reserving most of the carbohydrates. After enzymatic hydrolysis, the yields of glucose and xylose were 78.5 % and 69.3 %, respectively. The simultaneous saccharification and fermentation of pretreated CS using Pichia stipitis resulted in an ethanol concentration of 36.1 g/L, corresponding only to 63.3 % of the theoretical maximum. In order to simplify the process and reduce the capital cost, the liquid fraction of the pretreatment was used to re-soak new CS. For methane production, the re-soaked CS and the residues of SSF were anaerobically digested for 120 days. Fifteen grams CS were converted to 1.9 g of ethanol and 1337.3 mL of methane in the entire process. PMID- 22669689 TI - Religion and BMI in Australia. AB - We estimated the relationship between religion and body mass index (BMI) for a general and representative sample of the Australia population. Data from the Household Income Labour Dynamics survey were analysed for 9,408 adults aged 18 and older. OLS regression analyses revealed that religious denomination was significantly related to higher BMI, after controlling for socio-demographic, health behaviours, and psychosocial variables. 'Baptist' men had, on average, a 1.3 higher BMI compared to those reporting no religious affiliation. Among women, 'Non-Christians' had, on average, a 1 unit lower BMI compared to those reporting no religious affiliation while 'Other Christian' women reported, on average, a 1 unit higher BMI. Our results also indicate that there was a negative relationship between religious importance and BMI among Australian women. PMID- 22669690 TI - The clinical treatment of childhood obesity. AB - With the rising prevalence of childhood obesity, pediatricians are increasingly called upon to treat clinically overweight children. The primary treatment options are behavioral lifestyle modification, pharmacotherapy, and surgery. The cornerstone of childhood obesity treatment is lifestyle modification and has been shown to be effective in improving the severity of overweight and obesity. Several guidelines discuss appropriate methods for lifestyle modification in overweight and obese children. This review will summarize three recent guidelines/recommendations (released by the Scottish Intercollegiate Network, the American Academy of Pediatrics, and the United Kingdom National Institute for Health and Clinical Excellence) and describe by way of example, a current child obesity treatment program in the United States (Duke University Medical Center). Finally, evidence for pharmacologic and surgical treatment options will also be discussed, which can be valuable treatment options for select patients. PMID- 22669691 TI - Renal cortical necrosis and acute kidney injury associated with Plasmodium vivax: a neglected human malaria parasite. AB - Plasmodium vivax is causing increasingly more cases of severe malaria worldwide. There is an urgent need to reexamine the clinical spectrum and burden of P. vivax so that adequate control measures can be implemented against this emerging but neglected disease. Herein, we report a case of renal acute cortical necrosis and acute kidney injury (AKI) associated with P. vivax monoinfection. Her initial serum creatinine was 7.3 mg/dL on admission. Modification of Diet in Renal Disease (MDRD) Study glomerular filtration rate (GFR) value was 7 mL/min/1.73 m(2) (normal kidney function-GFR above 90 mL/min/1.73 m(2) and no proteinuria). On follow-up, 5 months later, her SCr. was 2.43 mg/dl with no proteinuria. MDRD GFR value was 24 mL/min/1.73 m(2) suggesting severe chronic kidney disease (CKD; GFR less than 60 or kidney damage for at least 3 months), stage 4. Our case report highlights the fact that P. vivax malaria is benign by name but not always by nature. AKI associated with P. vivax malaria can lead to CKD. Further studies are needed to determine why P. vivax infections are becoming more severe. PMID- 22669692 TI - Effects of fipronil on dogs over Triatoma infestans, the main vector of Trypanosoma cruzi, causative agent of Chagas disease. AB - Chagas disease is the most important endemic disease in Latin America, mainly transmitted by Triatoma infestans in the Southern Cone countries of South America. Dogs are one of the main domestic reservoirs of Trypanosoma cruzi, the etiological agent of Chagas disease. The presence of dogs in rural households of endemic areas significantly increases the likelihood of the vectorial transmission of the parasite. We studied the mortality and blood intake of T. infestans exposed to dogs treated with different doses and formulations of fipronil. Two doses, two formulations, and different distances to the application point of fipronil were compared. Third instar nymphs of T. infestans were fed at different time intervals after the insecticide application up to 45 days post application. No significant difference was found between the blood intake of nymphs fed on control and treated dogs with different doses and formulations (p > 0.05). The spray formulation showed lower effect and persistence than the spot-on formulation. The mortality rate caused by the spot-on formulation in the 26.8-mg active ingredient (a.i.)/kg dose was higher (48%) than with the 13.4-mg a.i./kg dose (25%), 24 h after the insecticide application. The effect was highly heterogeneous among replicates of the same treatment. The mortality rate of nymphs fed over the point of the insecticide application was higher than the mortality of nymphs fed over places 12 cm apart from the fipronil application point, suggesting that the distribution of fipronil over the dog body is lower than the needed one to obtain a persistent triatomicide effect. PMID- 22669693 TI - The second transcribed spacer rDNA sequence: an effective genetic marker for inter-species phylogenetic analysis of trematodes in the order Strigeata. AB - In the present study, the second nuclear internal transcribed spacer (ITS-2) rDNA of Schistosoma japonicum isolates in mainland China was amplified, sequenced, and assessed for inferring the intra- and inter-species phylogenetic relationships of trematodes in the order Strigeata. The fragment containing ITS-2 rDNA was obtained from 24 S. japonicum isolates from eight epidemic provinces in mainland China. The length polymorphisms were observed among these ITS-2 rDNA sequences, ranging from 343 to 346 bp, and the intra- and inter-population variations in ITS 2 sequence were 0.0-2.1% among S. japonicum isolates in China. Phylogenetic analyses using the maximum parsimony and maximum likelihood methods revealed that the ITS-2 rDNA sequence is not a suitable marker for studying inter- and intra population variation in S. japonicum. However, phylogenetic analysis of trematodes in the order Strigeata indicated that the ITS-2 rDNA sequence provides an effective molecular marker for studying inter-species phylogenetic relationships among trematodes in this order. PMID- 22669694 TI - Canine visceral leishmaniasis: relationships between oxidative stress, liver and kidney variables, trace elements, and clinical status. AB - The aim of this study was to investigate the role of oxidative stress in the pathology of canine visceral leishmaniasis (CVL). We therefore studied the relationships between oxidative stress markers, liver and kidney variables, trace elements, and clinical status in dogs naturally infected with Leishmania infantum. Two groups of Leishmania-infected dogs [asymptomatic (AD, n = 14) and symptomatic (SD, n = 16)] were assessed and compared with a group of non-infected control dogs (CD, n = 30). A significant decrease (p < 0.001) in serum total antioxidant status (TAS) and albumin concentration (p < 0.05) and a significant increase in serum malondialdehyde (MDA) and blood urea nitrogen (BUN) concentrations (p < 0.001), in the SD group, were observed when compared to CD and AD groups. Dogs of the AD group presented a significant decrease in copper (p < 0.01) and zinc (p < 0.001) concentrations, when compared to CD group, while the SD group presented a significant decrease (p < 0.001) in copper and zinc concentrations, when compared to CD and AD groups. Oxidative stress markers (MDA and TAS) showed significant correlations (p < 0.001) with trace elements (copper and zinc) and liver (alanine aminotransferase) and kidney (BUN and creatinine) variables. The results of the present study revealed that symptomatic dogs showed more severe oxidative stress than asymptomatic and non-infected dogs and enhanced lipid peroxidation may be linked to liver and kidney damage in canine visceral leishmaniasis. PMID- 22669698 TI - [74-year-old woman with white fingers]. PMID- 22669695 TI - Development of a real-time PCR assay for the detection of Clonorchis sinensis DNA in gallbladder bile and stone samples from patients with cholecystolithiasis. AB - High prevalence of cholecystolithiasis in parts of East Asia has been postulated to be associated with Clonorchis sinensis infection. This study describes the development of a TaqMan-based real-time PCR assay for the detection of C. sinensis DNA in gallbladder bile and stone samples from patients with cholecystolithiasis. Primers and probe targeting the cytochrome c oxidase subunit 1 gene of mitochondrial DNA proved to be highly specific for C. sinensis and did not amplify other related heterogeneous DNA samples. The detection limit of this assay was 0.1 pg of adult C. sinensis genomic DNA. All of the egg-positive samples determined by microscopy yielded positive results by real-time PCR assay and that genetic testing of gallbladder stones using real-time PCR was considered as the most effective means for assessing C. sinensis infection status. This assay not only contributes to a greater understanding of stone pathogenesis but also benefits patients with cholecystolithiasis by facilitating effective diagnosis, treatment, and relapse prevention. PMID- 22669697 TI - [Fetal renal failure after intrauterine exposure to inhibitors of the renin angiotensin system]. AB - HISTORY AND AIM: A 36-year-old woman (primigravida, nullipara) at 25 + 3 weeks of gestation and a 27-year-old (primigravida, nullipara) at 22 + 7 weeks of gestation presented with oligo-/anhydramnios at our department of obstetrics. Both patients suffered from diabetes type 1 and 2, respectively, complicated by diabetic nephropathy, renal hypertension and retinopathy. The first woman had received an AT1 receptor antagonist and a beta blocker, the other one an ACE inhibitor and a beta blocker. At initial clinical examination both patients were in a good general state of health. Respiration, pulse and blood pressure were within normal limits. INVESTIGATIONS: Sonography showed oligy-/anhydramnion with enlarged echogenic kidneys of both fetuses. Having ruled out premature rupture of the membranes the reduced amount of amniotic fluid was interpreted as a consequence of the antihypertensive medication. TREATMENT AND COURSE: The medication was changed to methyldopa which resulted in an adequate and moderate increase of amniotic fluid in both patients. At post partum examination renal failure was confirmed in both infants. The first infant, now a boy at the age of two years, still suffers from chronic renal failure, needing antihypertensive medication with an ACE blocker. Follow-up of the second baby has so far shown normal growth of the kidneys and normotensive blood pressure. CONCLUSION: When planning a pregnancy, a preexisting hypertension should be treated with either methyldopa (1st choice) or a beta blocker as a second choice (e. g. Metoprolol). In patients who are treated with ACE blockers or AT1 antagonists, medication should be changed as soon as the pregnancy is ascertained. PMID- 22669699 TI - [Open and endovascular repair of abdominal aortic aneurysms - clinical picture, evidence, results]. PMID- 22669700 TI - [Nutrition in pregnancy - Practice recommendations of the Network "Healthy Start - Young Family Network"]. AB - Nutrition, physical activity and lifestyle in pregnancy influence maternal and child health. The "Healthy start - Young Family Network" supported by the German Government with the national action plan IN FORM developed recommendations on nutrition in pregnancy. Energy needs increase by only ~10 % by the end of pregnancy whereas micronutrient needs increase much more. Normal weight should preferably be achieved before pregnancy. Dietary recommendations follow those for the general population. Folic acid supplements (400 ug/day) should be started before pregnancy and continue for at least the first trimester. Iodine rich foods and salt and an iodine supplement (100-150 ug/day) are recommended. Long-chain omega-3 fatty acids should be provided with >= 1 weekly portion of oily sea fish, or a DHA-supplement if regular fish consumption is avoided. Vitamin D supplementation is advisable unless there is regular exposure to sunlight. Health care professions should lead parents to health-promoting lifestyles. Subjects of part 2 of the article are practice recommendations on nutrition in pregnancy, especially vegetarian diets, recommendations on micronutrient supplementation, risk reduction of listeriosis and toxoplasmosis, alcohol, tobacco, caffeine and physical activity in pregnancy. PMID- 22669701 TI - [Antibiotics - quo vadit?]. PMID- 22669702 TI - [Increased lipase levels]. PMID- 22669703 TI - [Vaccination against rabies: how and when?]. PMID- 22669705 TI - In vivo evaluation of doxorubicin-loaded (PEG)(3)-PLA nanopolymersomes (PolyDoxSome) using DMBA-induced mammary carcinoma rat model and comparison with marketed LipoDoxTM. AB - PURPOSE: To evaluate in vivo doxorubicin-loaded (PEG)(3)-PLA nanopolymersomes (PolyDoxSome) using 7,12-dimethyl benz[alpha]anthracene (DMBA)-induced mammary carcinoma rat model compared to marketed formulation LipoDoxTM. METHODS: Sprague Dawley female rats with mean tumor volume of about 2 cm(3) were used for pharmacokinetics, biodistribution, antitumor efficacy and toxicity studies. RESULTS: This study demonstrates that PolyDoxSome has higher AUC (569 vs. 4 h*MUg/mL), longer plasma circulation half life (21.9 vs. 0.49 h), decreased clearance (10.5 vs. 1579 mL/h/kg) and volume of distribution (137.7 vs. 1091 mL/kg) as compared to free doxorubicin. Tissue distribution profile showed increased doxorubicin concentration in tumor and decreased concentration in heart as compared to free doxorubicin. The toxicity studies as measured from liver function tests, cardiac enzyme assays, hematology test and body weight has demonstrated that it is better tolerated than free doxorubicin. When PolyDoxSome was compared with LipoDoxTM, it differs in size (171 vs. <100 nm), plasma circulation half life (22 vs. 35 h), C(max) (34 vs. 67 MUg/mL), and AUC (568 vs. 2291 h*MUg/mL), however PolyDoxSome was comparable on efficacy and toxicity profile of LipoDoxTM. CONCLUSIONS: Results suggest that PolyDoxSome has better in vivo profile than free doxorubicin and comparable efficacy and toxicity to LipoDoxTM. PMID- 22669706 TI - Random mutagenesis of beta-tubulin defines a set of dispersed mutations that confer paclitaxel resistance. AB - PURPOSE: Previous research showed that mutations in beta1-tubulin are frequently involved in paclitaxel resistance but the question of whether the mutations are restricted by cell-type specific differences remains obscure. METHODS: To circumvent cellular constraints, we randomly mutagenized beta-tubulin cDNA, transfected it into CHO cells, and selected for paclitaxel resistance. RESULTS: A total of 26 beta1-tubulin mutations scattered throughout the sequence were identified and a randomly chosen subset were confirmed to confer paclitaxel resistance using site-directed mutagenesis of beta-tubulin cDNA and transfection into wild-type cells. Immunofluorescence microscopy and biochemical fractionation studies indicated that cells expressing mutant tubulin had decreased microtubule polymer and frequently suffered mitotic defects that led to the formation of large multinucleated cells, suggesting a resistance mechanism that involves destabilization of the microtubule network. Consistent with this conclusion, the mutations were predominantly located in regions that are likely to be involved in lateral or longitudinal subunit interactions. Notably, fourteen of the new mutations overlapped previously reported mutations in drug resistant cells or in patients with developmental brain abnormalities. CONCLUSIONS: A random mutagenesis approach allowed isolation of a wider array of drug resistance mutations and demonstrated that similar mutations can cause paclitaxel resistance and human neuronal abnormalities. PMID- 22669708 TI - No difference in 9-year outcome in CLBP patients randomized to lumbar fusion versus cognitive intervention and exercises. AB - PURPOSE: To compare the 9-year outcome in patients with chronic low back pain treated by instrumented lumbar fusion versus cognitive intervention and exercises. METHODS: The main outcome measure was the Oswestry Disability Index (ODI). Secondary outcome measures included pain, fear-avoidance beliefs, trunk muscle strength, medication, and return to work. RESULTS: One-third of the patients randomized to cognitive intervention and exercises had crossed over and been operated and one-third of the patients allocated to lumbar fusion had been re-operated. The intention-to-treat analysis detected no differences between the two groups. The mean adjusted treatment effect for ODI was 1.9 (95 % CI -7.8 to 11.6). Analysed according to the treatment received, more operated patients used pain medication and were out of work. CONCLUSIONS: The outcome at 9 years was not different between instrumented lumbar fusion and cognitive intervention and exercises. PMID- 22669709 TI - Retinal vasculitis associated with pyoderma gangrenosum: a case report. PMID- 22669711 TI - Where does brentuximab vedotin fit into the management of patients with Hodgkin lymphoma? AB - Brentuximab vedotin is an antibody-drug conjugate that targets CD30 and links monomethyl auristatin E, a microtubule disrupting agent, to an anti-CD30 monoclonal antibody. A phase II study of brentuximab vedotin in relapsed/refractory classical Hodgkin lymphoma (cHL) showed an impressive overall response rate of 75 % with 34 % complete responses, and median remission duration of 20 months in complete responders. In addition, brentuximab vedotin has very modest toxicity in heavily pretreated patients, with reversible peripheral neuropathy being the most common side effect. Brentuximab vedotin received accelerated FDA approval in August 2011 for use as a salvage therapy in cHL following failure of at least two prior therapies. Brentuximab vedotin is the treatment of choice for patients relapsing after stem cell transplant and for patients refractory to standard salvage regimens pre-transplant. Because of high single-agent activity and limited side effects, brentuximab vedotin has emerged as an ideal drug to test in combination therapy for cHL. Current trials are examining the use of brentuximab vedotin in frontline combination regimens, as salvage therapy prior to stem cell transplant, and as adjuvant treatment post transplant. Such studies will help clarify the optimal use of brentuximab vedotin in the treatment paradigm for Hodgkin lymphoma. PMID- 22669710 TI - Inactivation of the constitutively active ghrelin receptor attenuates limbic seizure activity in rodents. AB - Ghrelin is a pleiotropic neuropeptide that has been recently implicated in epilepsy. Animal studies performed to date indicate that ghrelin has anticonvulsant properties; however, its mechanism of anticonvulsant action is unknown. Here we show that the anticonvulsant effects of ghrelin are mediated via the growth hormone secretagogue receptor (GHSR). To our surprise, however, we found that the GHSR knockout mice had a higher seizure threshold than their wild type littermates when treated with pilocarpine. Using both in vivo and in vitro models, we further discovered that inverse agonism and desensitization/internalization of the GHSR attenuate limbic seizures in rats and epileptiform activity in hippocampal slices. This constitutes a novel mechanism of anticonvulsant action, whereby an endogenous agonist reduces the activity of a constitutively active receptor. PMID- 22669712 TI - Preparation and characterization of artificial antigens for cadmium and lead. AB - Cadmium and lead were conjugated to two carrier proteins using a bifunctional chelator [2-(4-aminobenzyl)-diethylenetriaminepentaacetic acid] to synthesize artificial antigens for cadmium and lead. The techniques, including ultraviolet spectrometry, circular dichroism, sodium dodecyl sulfate polyacrylamide gel electrophoresis, and inductively coupled plasma optical emission spectroscopy, were utilized for characterizing the artificial antigens. The results of ultraviolet spectrometry showed characteristic absorption peak shifts between conjugates and carrier proteins. Circular dichroism resulted that the second structure of the conjugates was alpha-helix. The sodium dodecyl sulfate polyacrylamide gel electrophoresis results revealed the differences of band migration and molecular weight among antigens, chelator protein conjugate, and carrier proteins. The result of coupling ratios revealed that the metal content of the antigens was much higher than that of carrier proteins. These results indicated that the artificial antigens of cadmium and lead were synthesized successfully and had potential application in immunoassays of cadmium and lead ions. PMID- 22669713 TI - Species variation in small molecule components of animal vitreous. AB - PURPOSE: We characterized differences in biochemical composition of the vitreous of different animal species with respect to small molecule constituents. METHODS: Vitreous samples were extracted from sheep, pig, Dutch Belted rabbits, and New Zealand white rabbits. The vitreous samples were investigated for acetylcholinesterase (AChE) activity and, in addition, were subjected to metabolomics determination using mass spectrometry. RESULTS: AChE activity varied across the species investigated with greater activity noted in larger animals. Principal component analysis demonstrated species differentiation in relation to metabolomic profile. Key peaks identified the importance of animal diet on small molecule composition of the vitreous. CONCLUSIONS: Our results highlighted principal and consistent differences in small molecule composition and enzymatic activity of the vitreous depending on species. Interesting differences were demonstrated, showing that diet potentially can impact on components of and metabolites contained within the vitreous. Material will be exchanged between vascular and retinal tissue with the vitreous compartment and as a nonvascular, slowly equilibrating "sink" might reflect changes in transporter activity. As a first step, understanding the differences in the metabolic profile of vitreous from different species may impact interpretation of such activity across different species. PMID- 22669714 TI - Physiologic properties of Muller cells from human eyes affected with uveal melanoma. AB - PURPOSE: To study physiologic characteristics of human Muller cells from healthy and pathologically altered eyes. METHODS: Human tissue was used from organ donors and from patients affected with uveal melanoma. Several melanoma eyes also showed retinal detachment. Incubation of freshly prepared slices with a commercial vital dye preferentially stained Muller cells. The Muller cell response to hypotonic stress was observed by recording the cross-sectional area of cell somata. Electrophysiologic properties were investigated in parallel in whole-cell patch clamp experiments. RESULTS: Inward K+ currents mediated by inwardly rectifying Kir channels were significantly decreased in Muller cells from eyes with uveal melanoma compared with healthy controls. This was accompanied by a decrease of the membrane potential. Both effects were stronger in cells from eyes where the melanoma had caused a widespread retinal detachment. Application of a hypotonic solution did not affect Muller cells from healthy organ donors. By contrast, Muller cells from some melanoma eyes increased their soma size in response to hypotonic solution. This effect was aggravated in cells from eyes with widespread retinal detachment. The inflammatory mediator, arachidonic acid, could induce Muller cell swelling, whereas anti-inflammatory substances reduced the swelling. CONCLUSIONS: The experiments with human tissue confirm earlier data from animal models for retinal pathologies about typical alterations of reactive Muller cells. Hypotonic stress induced Muller cell swelling preferentially in cells from melanoma-affected eyes that displayed decreased inward current amplitudes. Widespread melanoma-associated retinal detachment potentiated the pathologic alterations of Muller cells. PMID- 22669716 TI - Evaluation of sirtuin role in neuroprotection of retinal ganglion cells in hypoxia. AB - PURPOSE. Hypoxia-induced apoptosis is responsible for reduced retinal ganglion cell (RGC) viability in a variety of chronic ocular disorders. Sirtuin 1 (SIRT1) plays an important role in preserving cell viability during hypoxia. We investigated the role of SIRT1 in sustaining RGC viability in an in vitro model of hypoxia. METHODS. Staurosphorine-differentiated RGCs (RGC-5) received varying hypoxic concentrations (100-500 MUM) of cobalt chloride (CoCl2) for 24 hours. Hypoxia-induced cell viability was assessed by WST-1 assay. The role of SIRT1 in promoting viability was determined indirectly via sirtinol (SIRT1 inhibitor). Hypoxia-induced apoptosis was evaluated by measuring stress-activated protein kinase/c-jun N-terminal kinase (SAPK/JNK) and caspase 3 activity. Vascular endothelial growth factor (VEGF) was measured to ascertain the influence of SIRT1. RESULTS. CoCl2 concentrations greater than 100 MUM resulted in significantly reduced RGC viability (P=0.01). CoCl2 treatment increased SIRT1 levels significantly (P<0.01): 100 (6.5-fold), 200 (6-fold), 300 (3.5-fold), and 400 MUM (4.5-fold). Phosphorylated SAPK/JNK increased 36-fold (200 MUM CoCl2 concentration), then plateaued at the 300- (25-fold) and 400-MUM (27.8-fold) CoCl2 concentrations (P<0.01). CoCl2 and sirtinol treatment increased Caspase 3 activity (P<0.05). VEGF release was significantly higher than control at the 100 MUM CoCl2 concentrations (P<0.01). Sirtinol reduced RGC viability, SIRT1 levels, and VEGF release (P<0.01) while having greater effect on SAPK/JNK phosphorylation. CONCLUSIONS. SIRT1 significantly influences RGC viability. Sirtinol's effect reflects the interaction SIRT1 has with apoptotic signaling proteins. This investigation demonstrated SIRT1 importance in forestalling the effects of hypoxia-induced apoptosis. PMID- 22669715 TI - Decreased IL-27 expression in association with an increased Th17 response in Vogt Koyanagi-Harada disease. AB - PURPOSE: IL-27 has emerged as an important regulator of proinflammatory T-cell responses in animal models. We investigated the pathophysiological role of IL-27 in Vogt-Koyanagi-Harada (VKH) disease. METHODS: IL-27P28 and EBI3 mRNA expression in peripheral blood mononuclear cells (PBMCs) were assayed by RT-PCR. Cytokines in the serum and supernatants of PBMCs, naive CD4(+) T cells and DC-T cocultures were assayed by ELISA. Flow cytometry was used to evaluate the frequencies of IL 17-producing CD4(+) T cells. RESULTS: The active VKH patients showed a decreased IL-27P28 mRNA expression in PBMCs and lower IL-27 expression in the serum and supernatants of PBMCs, but higher Th17 cells in PBMCs. EBI3 mRNA expression was not different among the groups tested. Stimulation of naive CD4(+) T cells under Th17 polarizing conditions showed a higher Th17 cell differentiation in active VKH patients. IL-27 significantly inhibited Th17 cell differentiation. IL-27 treated DCs showed a significant inhibition on Th17 differentiation. There was a significant defect in the Tr1 cell induction as measured by IL-10 in active VKH patients. Treatment with corticosteroids and cyclosporine A (CsA) resolved the intraocular inflammation in association with an upregulation of IL-27 and a downregulation of IL-17. In vitro experiments showed that corticosteroids, but not CsA, significantly upregulated the expression of IL-27. CONCLUSIONS: The present study suggests that decreased IL-27 expression may result in a higher Th17 in active VKH patients, which may promote the autoimmune response observed in these patients. Manipulation of IL-27 may offer a novel target for treatment of this disease. PMID- 22669717 TI - JARID1B protein expression and prognostic implications in uveal melanoma. AB - PURPOSE: It has been suggested recently that stem cell marker expression of jumonji AT-rich interactive domain 1B (JARID1B) is required for continuous tumor growth and maintenance in human cutaneous melanoma cells. The aim of this study is to determine whether JARID1B is also expressed in uveal melanoma (UM) and whether JARID1B marks an expanded cancer stem cell pool in poor prognosis UM. Based on the available data, this is the first time JARID1B expression in UM has been studied. METHODS: A total of 121 consecutive patients diagnosed with UM and who underwent enucleation were included in the study. Immunohistochemical staining with JARID1B antibodies was performed and immunoreactivity was assessed. Correlations of JARID1B expression with established clinicopathological parameters and overall survival (OS) were evaluated in univariate and multivariate analyses. RESULTS: JARID1B positive expression, as defined by >0% staining, was present in 55% of UMs and invariably in ciliary body epithelium. The correlation between JARID1B negative expression and JARID1B expression >5% inside the tumor tissue and OS was borderline statistically significant based on LogRank test at 5% significance level (P = 0.06). There were significantly more JARID1B positive cells in tumors with extrascleral extension than in tumors with no or minimal intrascleral invasion (P < 0.01, Mann-Whitney test). CONCLUSIONS: This study demonstrates that JARID1B is expressed by UM cells. Despite that JARID1B was highly expressed in UM, a statistically significant association (P < 0.05) between JARID1B expression and OS could not be obtained. However, a P-value of 0.06 could suggest that high JARID1B expression is correlated with lower survival; thus, a follow up study with a greater patient sample is recommended. In addition, samples of tumors characterized by high invasiveness showed a higher JARID1B expression. Furthermore, this study substantiates the presence of progenitor cells in the ciliary body epithelium. PMID- 22669718 TI - Effects of induced monocular blur versus anisometropic amblyopia on saccades, reaching, and eye-hand coordination. AB - PURPOSE: We previously showed that anisometropic amblyopia affects the programming and execution of saccades and reaching movements. In our current study, we investigated whether these amblyopia-related changes simply are due to a reduction in visual acuity alone by inducing artificial blur in one eye in visually-normal participants. METHODS: Twelve visually-normal participants performed saccades and reach-to-touch movements to targets presented on a computer screen during binocular and monocular viewing. A contact lens was used to blur the vision of one eye to a mean acuity level of 20/50. Saccades and reaching kinematics were compared before blur, immediately after blur, and 5 hours after blur was induced. The 5 hours after blur kinematic data from visually normal participants also were compared to those from 12 patients with anisometropic amblyopia who had comparable acuity in the amblyopic eye. RESULTS: Primary saccades (latency, amplitude, peak velocity), reaching movements (reaction time, movement time, peak acceleration, duration of the acceleration phase), and eye-hand coordination (saccade-to-reach planning interval, saccade-to reach peak velocity interval) were not affected by induced monocular blur in visually-normal participants, either immediately or 5 hours after blur. Compared to visually-normal participants after 5 hours of blur, patients with anisometropic amblyopia had significantly longer and more variable saccade latency during amblyopic eye viewing, lower peak acceleration, and a longer acceleration phase during reaching, and a different temporal pattern of eye-hand coordination. CONCLUSIONS: Artificially-induced monocular blur in visually-normal participants did not affect saccades, reaching movements, and eye-hand coordination during a simple reach-to-touch task even after a period of blur exposure. In contrast, patients with anisometropic amblyopia demonstrated significantly different kinematics while performing the same task. These results indicate that loss of visual acuity alone cannot explain the kinematic changes seen in patients with mild anisometropic amblyopia. PMID- 22669719 TI - Targeted administration into the suprachoroidal space using a microneedle for drug delivery to the posterior segment of the eye. AB - PURPOSE: This study seeks to determine the intraocular pharmacokinetics of molecules and particles injected into the suprachoroidal space of the rabbit eye in vivo using a hollow microneedle. METHODS: Suprachoroidal injections of fluorescein and fluorescently tagged dextrans (40 and 250 kDa), bevacizumab, and polymeric particles (20 nm to 10 MUm in diameter) were performed using microneedles in New Zealand white rabbits. The fluorescence intensity within the eye was monitored in each animal using an ocular fluorophotometer to determine the distribution of the injected material in the eye over time as compared with intravitreal injection of fluorescein. Fundus photography and histology were performed as well. RESULTS: Molecules and particles injected near the limbus using a microneedle flowed circumferentially around the eye within the suprachoroidal space. By targeting the suprachoroidal space, the concentration of injected materials was at least 10-fold higher in the back of the eye tissues than in anterior tissues. In contrast, intravitreal injection of fluorescein targeted the vitreous humor with no significant selectivity for posterior versus anterior segment tissues. Half-lives in the suprachoroidal space for molecules of molecular weight from 0.3 to 250 kDa ranged from 1.2 to 7.9 hours. In contrast, particles ranging in size from 20 nm to 10 MUm remained primarily in the suprachoroidal space and choroid for a period of months and did not clear the eye. No adverse effects of injection into the suprachoroidal space were observed. CONCLUSION: Injection into the suprachoroidal space using a microneedle offers a simple and minimally invasive way to target the delivery of drugs to the choroid and retina. PMID- 22669720 TI - The association between time spent outdoors and myopia using a novel biomarker of outdoor light exposure. AB - PURPOSE: We sought to determine whether conjunctival ultraviolet autofluorescence (UVAF), a biomarker of outdoor light exposure, is associated with myopia. METHODS: We performed a cross-sectional study on Norfolk Island and recruited individuals aged >= 15 years. Participants completed a sun-exposure questionnaire and underwent non-cycloplegic autorefraction. Conjunctival UVAF used a specially adapted electronic flash system fitted with UV-transmission filters (transmittance range 300-400 nm, peak 365 nm) as the excitation source. Temporal and nasal conjunctival UVAF was measured in both eyes using computerized photographic analysis with the sum referred to as "total UVAF." RESULTS: In 636 participants, prevalence of myopia decreased with an increasing quartile of total UVAF (P(trend) = 0.002). Median total UVAF was lower in subjects with myopia (spherical equivalent [SE] <= -1.0 diopter [D]) than participants without myopia: 16.6 mm(2) versus 28.6 mm(2), P = 0.001. In the multivariable model that adjusted for age, sex, smoking, cataract, height and weight, UVAF was independently associated with myopia (SE <= -1.0 D): odds ratio (OR) for total UVAF (per 10 mm(2)) was 0.81, 95% confidence interval (CI) 0.69 to 0.94, P = 0.007. UVAF was also significantly associated with myopia when analysis was restricted to subjects <50 years, and in moderate-severe myopia (SE <= -3.0 D). Prevalence of myopia decreased with increasing time outdoors (P(trend) = 0.03), but time outdoors was not associated with myopia on multivariable analysis. CONCLUSIONS: Study authors identified a protective association between increasing UVAF and myopia. The protective association of higher UVAF against myopia was stronger than that of increased levels of time spent outdoors as measured by this study's questionnaire. Future studies should investigate the association between UVAF and incident myopia, and its relationship to myopic progression. PMID- 22669721 TI - Circadian and wake-dependent effects on the pupil light reflex in response to narrow-bandwidth light pulses. AB - PURPOSE: Nonvisual light-dependent functions in humans are conveyed mainly by intrinsically photosensitive retinal ganglion cells, which express melanopsin as photopigment. We aimed to identify the effects of circadian phase and sleepiness across 24 hours on various aspects of the pupil response to light stimulation. METHODS: We tested 10 healthy adults hourly in two 12-hour sessions covering a 24 hour period. Pupil responses to narrow bandwidth red (635 +/- 18 nm) and blue (463 +/- 24 nm) light (duration of 1 and 30 seconds) at equal photon fluxes were recorded, and correlated with salivary melatonin concentrations at the same circadian phases and to subjective sleepiness ratings. The magnitude of pupil constriction was determined from minimal pupil size. The post-stimulus pupil response was assessed from the pupil size at 6 seconds following light offset, the area within the redilation curve, and the exponential rate of redilation. RESULTS: Among the measured parameters, the pupil size 6 seconds after light offset correlated with melatonin concentrations (P < 0.05) and showed a significant modulation over 24 hours with maximal values after the nocturnal peak of melatonin secretion. In contrast, the post-stimulus pupil response following red light stimulation correlated with subjective sleepiness (P < 0.05) without significant changes over 24 hours. CONCLUSIONS: The post-stimulus pupil response to blue light as a marker of intrinsic melanopsin activity demonstrated a circadian modulation. In contrast, the effect of sleepiness was more apparent in the cone contribution to the pupil response. Thus, pupillary responsiveness to light is under influence of the endogenous circadian clock and subjective sleepiness. PMID- 22669722 TI - Anti-inflammatory effects of alpha linolenic acid on human corneal epithelial cells. AB - PURPOSE: Systemic polyunsaturated fatty acids (PUFAs) were shown to improve the symptoms of dry eye syndrome due to their anti-inflammatory effects. This study evaluated the in vitro anti-inflammatory effects of PUFAs on human corneal epithelial (HCE) cells. METHODS: HCE cells were incubated for 2 hours with different concentrations of PUFAs: alpha-linolenic acid (ALA), gamma-linolenic acid (GLA), and linoleic acid (LA). Oleic acid (OA) and dexamethasone (DM) served as negative and positive controls, respectively. Cells were stimulated with either polyinosinic:polycytidylic acid (poly I:C) or lipopolysaccharide (LPS) complex. The protein contents and mRNA expression levels of IL-6, IL-8, IL-1beta, and TNF-alpha were evaluated with multiplex fluorescent bead immunoassay and real time PCR, respectively. The expression of inhibitory factor-kappaBalpha (I kappaBalpha) was evaluated with real-time PCR. RESULTS: The protein and mRNA levels of IL-6, IL-8, IL-1beta, and TNF-alpha were significantly increased after stimulation with LPS or poly I:C. Following treatment with ALA, a significant decrease was demonstrated in the protein content of TNF-alpha to 23.81% (P < 0.001), IL-6 to 46.71% (P < 0.001), IL-1beta to 20.86% (P < 0.05), and IL-8 to 52.21% (P < 0.001). Similar results were demonstrated at the mRNA level. The anti inflammatory effects of ALA were similar to those of DM for all of the pro inflammatory cytokines. The ALA inhibition of the pro-inflammatory cytokines was associated with a significant reduction of I-kappaBalpha. CONCLUSIONS: ALA may serve as a potent anti-inflammatory agent in ocular surface inflammation. The anti-inflammatory effects of ALA are comparable to those of corticosteroids, and are mediated through NF-kappaB signal transduction. PMID- 22669723 TI - Characterization of fusarium keratitis outbreak isolates: contribution of biofilms to antimicrobial resistance and pathogenesis. AB - PURPOSE: Fusarium is a major cause of microbial keratitis, and its ability to form biofilms was suggested as a contributing factor in recent outbreaks. We investigated the ability of outbreak Fusarium isolates (F. solani species complex [FSSC] and F. oxysporum species complex [FOSC]) to form biofilms in vitro and in vivo, and evaluated their antifungal susceptibilities. METHODS: Biofilm formation was assessed using our in vitro contact lens model and in vivo murine model. Biofilm architecture was assessed using confocal laser scanning microscopy (CLSM). Susceptibility against amphotericin B (AmB), voriconazole (VCZ), and natamycin (NAT) was determined using the CLSI-M38-A2 method and XTT metabolic assay. RESULTS: FSSC strains formed more biofilms than FOSC, in a strain- and clade-dependent manner. CLSM analyses revealed that "high biofilm forming" (HBF) strains had denser and thicker biofilms than "low biofilm forming" (LBF) strains of both species (thickness 51 vs. 41 MUm for FSSC and 61 vs. 45 MUm for FOSC strains, P < 0.05 for both comparisons). Fusarium biofilms exhibited species dependent antifungal susceptibilities (e.g., FSSC biofilms AmB minimal inhibitory concentrations [MIC] >=16 MUg/mL, while NAT or VCZ MICs were 2-8 MUg/mL). FSSC infected mice had severe corneal opacification independent of biofilm thickness, while FOSC infection resulted in moderate corneal opacification. Corneal fungal burden of mice infected with HBF strains was higher than those of the LBF strains. In contrast, the reference ATCC isolate was unable to cause infection. CONCLUSIONS: The ability to form biofilms is a key pathogenicity determinant of Fusarium, irrespective of the thickness of these biofilms. Further studies are warranted to explore this association in greater detail. PMID- 22669724 TI - Changes in diadenosine polyphosphates during alignment-fit and orthokeratology rigid gas permeable lens wear. AB - PURPOSE: To evaluate the levels of dinucleotides diadenosine tetraphosphate (Ap(4)A) and diadenosine pentaphosphate (Ap(5)A) in tears of patients wearing rigid gas permeable (RGP) contact lenses on a daily wear basis and of patients wearing reverse-geometry RGP lenses overnight for orthokeratology treatment. METHODS: Twenty-two young volunteers (10 females, 12 males; 23.47 +/- 4.49 years) were fitted with an alignment-fit RGP lens (paflufocon B) for a month, and after a 15-day washout period they were fitted with reverse-geometry RGP lenses for corneal reshaping (paflufocon D) for another month. During each period, tears were collected at baseline day 1, 7, 15, and 28. Ap(4)A and Ap(5)A were measured by high-pressure liquid chromatography (HPLC). Additionally, corneal staining, break-up time (BUT), Schirmer test, and dryness symptoms were evaluated. RESULTS: Ap(4)A concentrations increased significantly from baseline during the whole period of daily wear of RGP lenses (P < 0.001); concentration was also significantly higher than in the orthokeratology group, which remained at baseline levels during the study period except at day 1 (P < 0.001) and day 28 (P = 0.041). While BUT and Schirmer remained unchanged in both groups, discomfort and dryness were significantly increased during alignment-fit RGP daily wear but not during the orthokeratology period. CONCLUSIONS: Daily wear of RGP lenses increased the levels of Ap(4)A due to mechanical stimulation by blinking of the corneal epithelium, and this is associated with discomfort. Also, orthokeratology did not produce symptoms or signs of ocular dryness, which could be a potential advantage over soft contact lenses in terms of contact lens-induced dryness. PMID- 22669725 TI - Layer-specific manganese-enhanced MRI of the retina in light and dark adaptation. AB - PURPOSE: To employ functional manganese-enhanced MRI (MEMRI) to image layer specific changes in calcium-dependent activities in the rat retina during light versus dark adaptation. METHODS: Functional MEMRI at 20 * 20 * 700 MUm was used to study light and dark adaptation in the same animals (N = 10) in which one eye was covered and the fellow eye was not. The activity encoding of the light and dark adaptation was achieved in awake conditions and imaged under anesthesia. T(1)-weighted MRI at 11.7 tesla (T) was performed using two identical radiofrequency transceiver coils to allow interleaved MRI acquisitions of the two eyes. An intravascular contrast agent was also used to verify layer assignments. RESULTS: MEMRI detected contrasts among the inner retina, outer retina, and choroid. Independent confirmation of the vascular layers and boundaries between layers was documented with an intravascular contrast agent. The retinal layer thicknesses agreed with published data. The outer retina had lower MEMRI activity in light compared with dark adaption (P < 0.001), consistent with the increased metabolic demand associated with the "dark current." The inner retina had higher MEMRI activity in light compared with dark adaption (P < 0.05). The choroid MEMRI activity was not statistically different between light and dark adaptation (P > 0.05). CONCLUSIONS: This study demonstrated a high-resolution MEMRI protocol to image functional activities among different layers of the retinas in awake animals during light and dark adaptation. This approach could have potential applications in animal models of retinal dysfunction. PMID- 22669726 TI - In vivo imaging of lamina cribrosa pores by adaptive optics scanning laser ophthalmoscopy. AB - PURPOSE: To visualize and assess the surface-level pores of the lamina cribrosa in patients with glaucoma by using a prototype adaptive optics scanning laser ophthalmoscopy (AOSLO) system. METHODS: The numbers of laminar pores were compared between color disc photography, scanning laser ophthalmoscopy (SLO) without AO, and AOSLO. The pore area and elongation index were examined for correlation with ocular parameters such as the mean deviation, disc area, cup/disc ratio, disc ovality index, intraocular pressure (IOP), and axial length in the AOSLO images. RESULTS: The 40 eyes (20 normal and 20 glaucomatous) of 40 subjects were enrolled. The AOSLO provided laminar pore images of better quality than other imaging methods, and the number of visible pores was significantly greater in the AOSLO images than in the other imaging methods (the color disc photographs [P < 0.001] and SLO without AO images [P < 0.001]) when compared for 26 subjects. When compared for 40 subjects using AOSLO, the pore area was significantly larger in glaucomatous subjects than in normal subjects (P = 0.031), but elongation index was not. The pore area correlated significantly with the axial length (P = 0.008) in normal subjects, with the untreated IOPs (P = 0.002) in the glaucomatous subjects, and with the axial length (P = 0.001) and cup/disc ratio (P = 0.012) in the total subjects. Via multiple regression analysis, significant correlations with pore area were found for axial length in the normal (beta = 0.684, P = 0.001) and total subjects (beta = 0.496, P < 0.001) and untreated IOP in the glaucomatous (beta = 0.506, P = 0.023) and total subjects (beta = 0.331, P = 0.014). CONCLUSIONS: AOSLO is a useful imaging technology for assessing laminar pore morphology. The laminar pore area may be affected by axial length and IOP. PMID- 22669728 TI - Piperine suppresses cerebral ischemia-reperfusion-induced inflammation through the repression of COX-2, NOS-2, and NF-kappaB in middle cerebral artery occlusion rat model. AB - The pathophysiological mechanisms leading to neuronal injury in middle cerebral artery occlusion (MCAO) model of cerebral stroke are complex and multifactorial that form the bases of behavioral deficits and inflammation mediated damage. The present study demonstrates the effect of piperine pretreatment (10 mg/kg b wt, once daily p.o. for 15 days) on cerebral ischemia-induced inflammation in male Wistar rats. The right middle cerebral artery was occluded for 2 h followed by reperfusion for 22 h. A maximum infarct volume (57.80 %) was observed in ischemic MCAO group. However, piperine administration prior to ischemia showed a significant reduction in infarct volume (28.29 %; p < 0.05) and neuronal loss (12.72 %; p < 0.01). As a result of piperine pretreatment, a significant improvement in behavioral outputs of MCAO rats (p < 0.05-0.01) was observed. Piperine successfully reduced the level of proinflammatory cytokines IL-1beta, IL 6 and TNF-alpha, in ischemic group (p < 0.01). Ischemic group brain has shown edematous morphology with vacuolated architecture and pyknotic nuclei in H & E staining which was successfully ameliorated by piperine administration. Moreover, piperine also succeeded in lowering the expression of COX-2, NOS-2, and NF-kappaB (p < 0.01). Both cytosolic and nuclear NF-kappaB were down-regulated in ischemic group pre-administered with piperine (p < 0.01). The present study suggests that piperine is able to salvage the ischemic penumbral zone neurons by virtue of its anti-inflammatory property, thereby limiting ischemic cell death. PMID- 22669729 TI - A missense mutation in CRYGD linked with autosomal dominant congenital cataract of aculeiform type. AB - To detect the underlying genetic defects in two autosomal dominant congenital cataract (ADCC) families, having respectively twenty and four members affected with bilateral congenital cataract. Detailed family history and clinical data were recorded. Mutation screening in twenty three candidate genes including crystallins (CRYAA, CRYAB, CRYBA1/A3, CRYBA2, CRYBA4, CRYBB1, CRYBB2, CRYBB3, CRYGA, CRYGB, CRYGC, CRYGD, and CRYGS), gap junctional channels; connexins (GJA8, GJA3), beaded filament chain proteins (BFSP1, BFSP2), major intrinsic protein (MIP), lens intrinsic membrane protein-2 (LIM2), transcriptional factor (MAF), and in genes encoding for membrane-associated proteins (TMEM114, CHMP4B, EPHA2) was performed by bi-directional sequence analysis of the amplified products. In family A twenty members in six generations were affected by bilateral aculeiform type cataract and in family B four affected members in three generations had granular nuclear cataract. Mutation screening in already known candidate genes by sequence analyses revealed proline to threonine substitution at codon 23 (p.Pro23Thr) in CRYGD for aculeiform type cataract in family A. The family B with four members affected by granular nuclear cataract, however, could not be linked with any of these analyzed 23 candidate genes. The present study describes identification of p.Pro23Thr mutation in CRYGD for aculeiform type cataract in an ADCC family of Indian origin. The identical mutation has previously been reported to be linked with different phenotypes; lamellar cataract, cerulean cataract, coralliform cataract, flaky silica-like nuclear cataract and fasciculiform type cataract in different ADCC families. Interestingly, a mutation of different codon, i.e., p.Arg58His in CRYGD has been reported to be linked with aculeiform cataract in four different families; two from Switzerland, one from Macedonia and in a Mexican family. The findings in present study thus expand the genetic heterogeneity for aculeiform type cataract. Further, exclusion of these twenty three known candidate genes in family B having ADCC of granular nuclear type indicates the role of some other gene apart from for crystallins, gap junction channels, beaded filaments and membrane-associated proteins, and MAF for this phenotype. PMID- 22669731 TI - Usefulness of IDEAL T2-weighted FSE and SPGR imaging in reducing metallic artifacts in the postoperative ankles with metallic hardware. AB - PURPOSE: The aim of this work is to prospectively compare the effectiveness of iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL), T2-weighted fast spin-echo (FSE), and spoiled gradient-echo (SPGR) MR imaging to frequency selective fat suppression (FSFS) protocols for minimizing metallic artifacts in postoperative ankles with metallic hardware. MATERIALS AND METHODS: The T2-weighted and SPGR imaging with IDEAL and FSFS were performed on 21 ankles of 21 patients with metallic hardware. Two musculoskeletal radiologists independently analyzed techniques for visualization of ankle ligaments and articular cartilage, uniformity of fat saturation, and relative size of the metallic artifacts. A paired t test was used for statistical comparisons of MR images between IDEAL and FSFS groups. RESULTS: IDEAL T2 weighted FSE and SPGR images enabled significantly improved visualization of articular cartilage (p < 0.05), the size of metallic artifact (p < 0.05), and the uniformity of fat saturation (p < 0.05). However, no significant improvement was found in the visibility of ligaments. CONCLUSIONS: IDEAL T2-weighted FSE and SPGR imaging effectively reduces the degree of tissue-obscuring artifacts produced by fixation hardware in ankle joints and improves image quality compared to FSFS T2 weighted FSE and SPGR imaging. However, visibility of ligaments was not improved using IDEAL imaging. PMID- 22669730 TI - Case report: Third-degree skin and soft tissue burn after radiofrequency ablation of an osteoid osteoma guided through a triple-crown biopsy cannula. PMID- 22669732 TI - 3 T DCE-MRI assessment of synovitis of the interphalangeal joints in patients with erosive osteoarthritis for treatment response monitoring. AB - OBJECTIVE: To study the value of 3 T dynamic contrast-enhanced (DCE)-MRI for assessment of synovitis of the interphalangeal joints in patients with erosive osteoarthritis (EOA) for treatment response monitoring. MATERIALS AND METHODS: The interphalangeal joints of fingers two to five were examined at 3 T MRI in nine patients with EOA. Two musculoskeletal radiologists recorded erosions, bone marrow oedema (BME), synovitis and osteophytes. Interobserver reliability was calculated using kappa statistics. In six patients, DCE-MRI time intensity curves of synovitis in two affected joints were analysed. The maximum upslope, absolute and relative enhancement of synovitis were compared with MRI after 12 months of anti-tumour necrosis factor treatment. Intraobserver reproducibility was calculated using intra-class correlation coefficient. RESULTS: Interobserver reliability was 'good' for detection of erosions (kappa = 0.70), BME (kappa = 0.77) and synovitis (kappa = 0.77), but 'poor' for osteophytes (kappa = 0.12). Post-treatment DCE-MRI showed decreasing maximum upslope (p = 0.002) and absolute (p = 0.002) and relative (p = 0.01) enhancement compared to the initial scan. Intraobserver reproducibility of DCE-MRI was 'almost perfect' or 'strong' for all parameters. CONCLUSIONS: 3 T DCE-MRI demonstrates changes in time intensity curves of synovitis in EOA of the interphalangeal joints in a longitudinal study, indicating this technique is promising for monitoring therapy response. PMID- 22669733 TI - Use of the iPhone for radiographic evaluation of hallux valgus. AB - OBJECTIVE: The purpose of this study was to compare the measurements made using a smartphone accelerometer and computerized measurements as a reference in a series of 32 hallux valgus patients. MATERIALS AND METHODS: Two observers used an iPhone to measure the hallux valgus angle (HVA), intermetatarsal angle (IMA), and distal metatarsal articular angle (of anteroposterior foot radiographs in 32 patients with symptomatic hallux valgus on a computer screen. Digital angular measurements on the computer were set as the reference standard for analysis and comparison. The difference between computerized measurements and all iPhone measurements, and the difference between the first and second iPhone measurements for each observer were calculated. Inter- and intraobserver reliability of the smartphone measurement method was also tested. RESULTS: The variability of all measurements was similar for the iPhone and the computer-assisted techniques. The concordance between iPhone and computer-assisted angular measurements was excellent for the HVA, IMA, and DMAA. The maximum mean difference between the two techniques was 1.25 +/- 1.02 degrees for HVA, 0.92 +/- 0.92 degrees for IMA, and 1.10 +/- 0.82 degrees for DMAA. The interobserver reliability was excellent for HVA, IMA, and DMAA. The maximum mean difference between observers was 1.31 +/- 0.89 degrees for HVA, 0.90 +/- 0.92 degrees for IMA, and 0.78 +/- 0.87 degrees for DMAA. The intraobserver reliability was excellent for HVA, IMA, and DMAA. CONCLUSIONS: We conclude that the Hallux Angles software for the iPhone can be used for measurement of hallux valgus angles in clinical practice and even for research purposes. It is an accurate and reproducible method. PMID- 22669734 TI - Simulated caregivers: their feasibility in educating pharmacy staff to manage children's ailments. AB - BACKGROUND: Community pharmacy staff play a crucial role in the management of common childhood ailments. Simulated patient studies have not yet explored the management of children's cough/cold and fever, nor have many previous studies used simulated patient methods with focus on self-assessment as a training tool to shape future counselling behaviour. OBJECTIVES: To assess and shape the counselling behavior of pharmacy staff when dealing with children's cough/cold and fever; investigate influential factors of counselling behavior; and explore participant perceptions of simulated patient methods as a training tool, with particular emphasis on self-assessment. SETTING: Community pharmacies in the inner city region of metropolitan Sydney. METHOD: Six simulated caregivers visited eight community pharmacies. After applying their scenario, the interaction was scored and immediate performance feedback was delivered in the form of self-assessment. Semi-structured interviews followed, focusing on participant perceptions of self-assessment. MAIN OUTCOME MEASURES: Scores for each simulated patient interaction, and qualitative interviews responses from participants. RESULTS: The highest mean percentage score achieved was for the symptom based request for a cough/cold remedy in a five year old (48 +/- 14.3 %), while the lowest was the direct product request equivalent (22 +/- 8.5 %). Qualitative results showed that simulated patient visits were viewed positively and self-assessment was highly regarded. CONCLUSION: Using simulated caregivers in pharmacy to assess and improve children's cough/cold and fever management is feasible and acceptable. The opportunity to self-assess is particularly beneficial, allowing participants to demonstrate key psychology principles associated with behaviour change. PMID- 22669735 TI - Infraareolar access for thoracoscopic sympathectomy to treat primary hyperhidrosis. AB - We herein present a new technique for performing thoracoscopic sympathectomy to treat primary hyperhidrosis in both genders and all ages through the mammary infraareolar access associated with the axillary access. We believe that these points of access are feasible and safe, and result in an excellent cosmetic outcome without compromising the efficacy of the thoracoscopic sympathectomy. The existence of adhesions between the parietal and visceral pleura, the presence of large breasts, and lactation made it difficult to perform the surgery, but did not make it impossible to apply the technique using the infraareolar access. However, the presence of breast implants is a contraindication for the new access. PMID- 22669736 TI - Assessment of global cardiac I-123 MIBG uptake and washout using volumetric quantification of SPECT acquisitions. AB - BACKGROUND: Assessment of cardiac innervation using single-photon emission computer tomography (SPECT) is less established than planar imaging, but may be more suitable for quantification. Therefore, a volumetric quantification of I-123 MIBG SPECT acquisitions was performed. Reproducibility, the effects of extra cardiac I-123 MIBG uptake and the relation with conventional planar indices were evaluated. METHODS: 54 patients referred for planar and SPECT I-123 MIBG acquisitions were included. Ellipsoidal or box-shaped volumes of interest were placed on the left ventricle, cardiac lumen, mediastinum, lung and liver. SPECT segmentation was performed twice in all patients. Indices were determined based on the heart-to-mediastinum (HM), myocardial wall-to-mediastinum and myocardial wall-to-lumen regions. HM ratios and washout rates were also determined based on anterior planar images. RESULTS: Cardiac count densities were highly reproducible (CV 1.5-5.4, ICC 0.96-0.99) and inter-rater variability was low (CV 1.8-6.8, ICC 0.94-0.99). Mediastinal uptake was an important explanatory variable of uptake in the entire heart (early R(2) = 0.36; delayed R(2) =0.43) and myocardial wall (early R(2) = 0.28; delayed R(2) = 0.37). Lung washout was an explanatory variable of organ washout of the heart (heart R(2) = 0.38; myocardial wall R(2) = 0.33). In general, SPECT indices showed moderate-to-good correlations with the planar uptake (PCC 0.497-0.851). CONCLUSION: By applying a volumetric segmentation method we were able to segment the heart in all patients. SPECT I 123 MIBG quantification was found to be highly reproducible and had a moderate to good correlation with the planar indices. PMID- 22669737 TI - SPECT myocardial perfusion imaging as an endpoint. PMID- 22669738 TI - [Data quality of unsupervised endothelial cell counting vs. reading centre analysis in multicentric clinical trials]. AB - PURPOSE: The aim of this study was to assess data quality from unsupervised endothelial cell counting in the multicentric setting. PATIENTS AND METHODS: We performed an endothelial cell counting trial with two fictitious trial sites. The trial protocol simply demanded for marking 30 cells for analysis. Analyses were performed with the cell counting tool as built into the Topcon SP-3000P specular microscope. The first centre consequently dotted 30 cells. The other centre continuously dotted more cells until 30 cells were included in the cell counting analysis. Both sites analysed the same 89 eyes of corneal outpatients and heathy volunteers. Both sites used a dedicated Topcon SP-3000P microscope. The image pairs from both sites were eventually printed, scanned and re-evaluated with a programme that evaluated all visible cells ("reading centre"). The agreement between both sites was statistically assessed by means of Pearson's correlation and Bland-Altman analysis. The same statistical assessments were also performed for the image pairs as analysed in the reading centre. RESULTS: The determined cell densities as reported by both trial sites differed by -65 % to 42 %. Furthermore, we also observed a systematic deviation between both sites. Consequently, the coefficient of determination from Pearson's correlation was only 0.947. However, the agreement was as high as 0.997 when the image pairs were analysed in the reading centre. Here the difference between the cell densities of the image pairs ranged from merely -15 % to 9 % with no systematic deviation. CONCLUSIONS: Unsupervised endothelial cell counting does not result in sufficiently objective endothelial cell denstiy estimations. Furthermore, the built-in analysis tools can introduce systematic errors. Both drawbacks can be overcome by a reading centre that evaluates all visible cells on the images. For this reason, we recommend the involvement of a reading centre in multicentric clinical trials on the corneal endothelium. PMID- 22669739 TI - Oxidative stress and dermal toxicity of iron oxide nanoparticles in vitro. AB - A number of commercially available metal/metal oxide nanoparticles (NPs) such as superparamagnetic iron oxide (SPION) are utilized by the medical field for a wide variety of applications. These NPs may able to induce dermal toxicity via their physical nature and reactive surface properties. We hypothesize that SPION may be toxic to skin via the ability of particles to be internalized and thereby initiate oxidative stress, inducing redox-sensitive transcription factors affecting/leading to inflammation. Due to the skin's susceptibility to UV radiation, it is also of importance to address the combined effect of UVB and NPs co-exposure. To test this hypothesis, the effects of dextran-coated SPION of different sizes (15-50 nm) and manufacturers (MicroMod, Rostock-Warnemunde, Germany and KTH-Royal Institute of Technology, Stockholm, Sweden) were evaluated in two cell lines: normal human epidermal keratinocytes (HEK) and murine epidermal cells (JB6 P(+)). HEK cells exposed to 20 nm (KTH and MicroMod) had a decrease in viability, while the 15 and 50 nm particles were not cytotoxic. HEK cells were also capable of internalizing the KTH particles (15 and 20 nm) but not the MicroMod SPION (20 and 50 nm). IL-8 and IL-6 were also elevated in HEK cells following exposure to SPION. Exposure of JB6 P(+) cells to all SPIONs evaluated resulted in activation of AP-1. Exposure to SPION alone was not sufficient to induce NF-kappaB activation; however, co-exposure with UVB resulted in significant NF-kappaB induction in cells exposed to 15 and 20 nm KTH SPION and 50 nm MicroMod particles. Pre-exposure of JB6 P(+) cells to UVB followed by NPs induced a significant depletion of glutathione, release of cytokines, and cell damage as assessed by release of lactate dehydrogenase. Altogether, these data indicate that co-exposure to UVB and SPIONs was associated with induction of oxidative stress and release of inflammatory mediators. These results verify the need to thoroughly evaluate the adverse effects of UVB when evaluating dermal toxicity of engineered NPs on skin. PMID- 22669740 TI - Direct regulation of the proglucagon gene by insulin, leptin, and cAMP in embryonic versus adult hypothalamic neurons. AB - The proglucagon gene is expressed not only in the pancreas and intestine but also in the hypothalamus. Proglucagon-derived peptides have emerged as potential regulators of energy homeostasis. Whether leptin, insulin, or cAMP activation controls proglucagon gene expression in the hypothalamus is not known. A key reason for this has been the inaccessibility of hypothalamic proglucagon expressing neurons and the lack of suitable neuronal cell lines. Herein we describe the mechanisms involved in the direct regulation of the proglucagon gene by insulin, leptin, and cAMP in hypothalamic cell models. Insulin, through an Akt dependent manner, significantly induced proglucagon mRNA expression by 70% in adult-derived mHypoA-2/10 neurons and significantly suppressed it by 45% in embryonic-derived mHypoE-39 neurons. Leptin, via the Janus kinase-2/ signal transducer and activator of transcription-3 pathway, caused an initial increase by 66 and 43% at 1 h followed by a decrease by 45 and 34% at 12 h in mHypoA-2/10 and mHypoE-39 cells, respectively. Furthermore, cAMP activation by forskolin up regulated proglucagon expression by 87% in mHypoE-39 neurons and increased proglucagon mRNA, through Epac activation, in the mHypoE-20/2 neurons. Specific regions of the proglucagon promoter were regulated by cAMP signaling, as determined by transient transfections, whereas mRNA stability assays demonstrate that insulin and leptin increase proglucagon mRNA stability in the adult cells. These findings suggest that insulin, leptin, and cAMP act directly, but differentially, on specific hypothalamic neurons to regulate proglucagon gene expression. Because proglucagon-derived peptides are potential regulators of energy homeostasis, an understanding of hypothalamic proglucagon neurons is important to further expand our knowledge of alternative feeding circuits. PMID- 22669741 TI - Expression and function of myometrial PSF suggest a role in progesterone withdrawal and the initiation of labor. AB - Progesterone (P4), acting through its receptor (PR), is essential for the maintenance of pregnancy. P4 acts by suppressing uterine contractility and the expression of contraction-associated proteins (CAP) such as connexin 43 (Cx43). P4 levels must be reduced or its actions blocked to allow the increased expression of CAP genes and the initiation of labor. Although the importance of progesterone in pregnancy has been known for about 80 yr, the fundamental mechanisms by which P4/PR maintains myometrial quiescence and by which this signaling is blocked at term labor remain to be determined. In this manuscript, we demonstrate that ligand-bound PR interacts with the Cx43 gene promoter through activator protein-1 transcription factors. We show that the ability of PR to repress Cx43 transcription is conferred through the recruitment of the PR coregulator, polypyrimidine tract binding protein-associated splicing factor (PSF), and the further recruitment of the yeast switch independent 3 homolog A/histone deacetylase corepressor complex. PSF expression is elevated during pregnancy but falls toward term as a result of increased mechanical stretch of the myometrium and a rise in the concentrations of circulating estrogen. These data together indicate that PSF is a critical regulator of P4/PR signaling and labor. We suggest that decreased PSF at term may result in a de-repression of PR transcriptional control of CAP genes and thereby contributes to a functional withdrawal of progesterone at term labor. PMID- 22669742 TI - ERbeta-mediated estradiol enhances epithelial mesenchymal transition of lung adenocarcinoma through increasing transcription of midkine. AB - Epithelial-mesenchymal transition (EMT) plays a specific role in the migration of tumor cells. Both estrogen and midkine (MK) have been thought to be important factors in promoting the progression of non-small-cell lung cancer (NSCLC) and can enhance EMT. Some evidence indicated the correlation between estradiol (E2) and MK, but the precise mechanism on their interreaction is unknown. Here, we try to clarify whether and how E2 regulates MK expression to promote EMT. We found that E2 increased MK mRNA expression in lung adenocarcinoma cells LTEP-a2 and A549 in a time-dependent manner. E2-induced MK expression was inhibited by the estrogen receptor (ER) antagonist ICI 182,780 and tamoxifen but not by phosphoinositide-3 kinase and MAPK inhibitors, suggesting a genomic mechanism of E2 on the regulation of MK transcription. Moreover, luciferase reporter and chromatin immunoprecipitation assays exhibited that E2 induced ERbeta recruitment to the estrogen response element in the MK promoter. Small interfering RNA to ERalpha and ERbeta revealed that ERbeta mainly mediated E2-induced MK transcription. Interestingly, E2 enhanced MK expression in accordance with increase of EMT, whereas knockdown of MK could block EMT under E2 stimulation. Importantly, through analyzing lung adenocarcinoma tissues, there was indeed a correlation among levels of E2, MK, and EMT-related protein expression. Taken together, we reported a previously unrecognized mechanism on E2 in the regulation of MK expression and proved that MK plays a pivotal role in progression of E2 regulated EMT. PMID- 22669743 TI - Negative regulation of pancreatic and duodenal homeobox-1 by somatostatin receptor subtype 5. AB - Somatostatin receptor subtype 5 (SSTR5) mediates the inhibitory effect of somatostatin and its analogs on insulin expression/secretion and islet cell proliferation. We provide biochemical and genetic evidence that SSTR5 exerted its physiological actions via down-regulating pancreatic and duodenal homeobox-1 (PDX 1), a beta-cell-specific homeodomain-containing transcription factor. Cotransfection of SSTR5 with PDX-1 resulted in dose-dependent inhibition of PDX-1 expression in human embryonic kidney 293 cells. SSTR5 agonist RPL-1980 inhibited PDX-1 expression and abolished glucagon-like peptide 1-stimulated PDX-1 expression in mouse insulinoma beta-TC-6 cells. SSTR5 knockdown by short hairpin RNA led to increased PDX-1 expression that was accompanied by enhanced insulin secretion stimulated by high glucose in beta-TC6 cells and alternated expressions of cell cycle proteins that favor cell proliferation in mouse insulinoma MIN6 cells. Quantitative RT-PCR analysis showed that cotransfected SSTR5 inhibited PDX 1 mRNA expression, whereas knockdown of SSTR5 increased PDX-1 mRNA expression. In addition, we found that cotransfected wild-type SSTR5 increased PDX-1 ubiquitination in human embryonic kidney 293 cells, whereas SSTR5 P335L, a hypofunctional single nucleotide polymorphism of SSTR5, inhibited PDX-1 ubiquitination. SSTR5 knockout resulted in increased expression of PDX-1, insulin, and proliferating cell nuclear antigen in the islets of sstr(-/-) mice. Immunohistochemistry analysis showed that SSTR5 P335L was associated with elevated expression of PDX-1 in human pancreatic neuroendocrine tumor. Taken together, our studies demonstrated that SSTR5 is a negative regulator for PDX-1 expression and that SSTR5 may mediate the inhibitory effects of somatostatin and its analogs on insulin expression/secretion and cell proliferation via down regulating PDX-1 at both transcriptional and posttranslational levels. PMID- 22669744 TI - Synthesis of 'cineole cassette' monoterpenes in Nicotiana section Alatae: gene isolation, expression, functional characterization and phylogenetic analysis. AB - The scent bouquets of flowers of Nicotiana species, particularly those of section Alatae, are rich in monoterpenes, including 1,8-cineole, limonene, beta-myrcene, alpha- and beta-pinene, sabinene, and alpha-terpineol. New terpene synthase genes were isolated from flowers of Nicotiana bonariensis, N. forgetiana, N. longiflora, and N. mutabilis. The recombinant enzymes synthesize simultaneously the characteristic 'cineole cassette' monoterpenes with 1,8-cineole as the dominant volatile product. Interestingly, amino acid sequence comparison and phylogenetic tree construction clustered the newly isolated cineole synthases (CIN) of section Alatae together with the catalytically similar CIN of N. suaveolens of section Suaveolentes, thus suggesting a common ancestor. These CIN genes of N. bonariensis, N. forgetiana, N. longiflora, and N. mutabilis are distinct from the terpineol synthases (TERs) of the taxonomically related N. alata and N. langsdorfii (both Alatae), thus indicating gene diversification of monoterpene synthases in section Alatae. Furthermore, the presence of CINs in species of the American section Alatae supports the hypothesis that one parent of the Australian section Suaveolentes was a member of the present section Alatae. Amino acid sequences of the Nicotiana CINs and TERs were compared to identify relevant amino acids of the cyclization reaction from alpha-terpineol to 1,8 cineole. PMID- 22669745 TI - Developmentally non-redundant SET domain proteins SUVH2 and SUVH9 are required for transcriptional gene silencing in Arabidopsis thaliana. AB - In plants, RNA-directed DNA methylation (RdDM) and related transcriptional gene silencing (TGS) involve members of the suppressor of variegation 3-9-homologous (SUVH) group of putative histone methyltransferases. Utilizing a reverse genetic approach in Arabidopsis thaliana, we demonstrate that two closely related SUVH members, SUVH2 and SUVH9, act partially non-redundant in RdDM. DNA methylation, transcript accumulation and association with histone modifications were analyzed at the endogenous RdDM target AtSN1 (a SINE-like retroelement) in suvh2 and suvh9 single as well as suvh2 suvh9 double mutants. SUVH2 was found to be required for full DNA methylation at AtSN1 in early seed development and was also higher expressed in seeds than at later developmental stages. SUVH9 had its impact on RdDM later during vegetative development of the plant and was also higher expressed during that stage than at earlier developmental stages. The strongest reduction of RdDM at AtSN1 was found in suvh2 suvh9 double mutant plants. Histone 3-lysine 9-dimethylation (H3K9me2) associated with AtSN1 was reduced only in the simultaneous absence of functional SUVH2 and SUVH9. Thus, SUVH2 and SUVH9 functions in RdDM and TGS are overlapping in spite of some developmental specialization. Pol V specific transcripts were reduced in suvh2 suvh9 plants. This might indicate a role of these SUVH proteins in Pol V complex recruitment. PMID- 22669746 TI - Delta subclass HD-Zip proteins and a B-3 AP2/ERF transcription factor interact with promoter elements required for expression of the Arabidopsis cytochrome c oxidase 5b-1 gene. AB - We have identified transcription factors that interact with a promoter region involved in expression of the Arabidopsis thaliana COX5b-1 gene, which encodes an isoform of the cytochrome c oxidase zinc binding subunit. Elements with the core sequence ATCATT, involved in induction by sugars, are recognized both in vitro and in one-hybrid assays in yeast by HD-Zip proteins from the delta subclass and, though less efficiently, by the trihelix transcription factor GT-3b. DistalB-like elements (CCACTTG), required for induction by abscisic acid (ABA), interact with ESE1, a member of the B-3 subgroup of AP2/ERF transcription factors. The HD-Zip protein Athb-21 and ESE1 are able to interact in yeast two-hybrid assays with the ABA responsive element binding factor AREB2/ABF4, which binds to a G-box absolutely required for expression of the COX5b-1 gene. Overexpression of the identified transcription factors in plants produces an increase in COX5b-1 transcript levels. Moreover, these factors are able to induce the expression of a reporter gene located in plants under the control of the relevant COX5b-1 promoter regions required for expression. Analysis of promoter regions of COX5b genes from different plant species suggests that the identified transcription factors were recruited for the regulation of COX5b gene expression at different stages during the evolution of dicot plants. PMID- 22669747 TI - Trichilemmoma arising in the nasal vestibule: report of three cases with special emphasis on the differential diagnosis. AB - Trichilemmoma is a benign cutaneous epithelial tumor with differentiation towards cells of the outer hair root sheath and usually presents as a small papule on the face of middle-aged or older adults. We herein report three cases of trichilemmoma located in the nasal vestibule, including two of the conventional type and one of the desmoplastic variant. To our knowledge, only one case of trichilemmoma arising in the nasal vestibule has been previously reported. Trichilemmoma must be included in the differential diagnosis of epithelial lesions arising in this location. This is particularly important in the case of the desmoplastic trichilemmoma, a tumor that resembles invasive carcinoma such as desmoplastic squamous cell carcinoma, sclerosing basal cell carcinoma, and trichilemmal carcinoma. The circumscription of the lesion, the architectural pattern of epithelial cell cords and small nests merging with a desmoplastic stroma in the central area of the tumor, the expression of CD34, and the lack of an obvious squamous differentiation or basaloid foci favor the diagnosis of desmoplastic trichilemmoma. All these features help to rule out the diagnosis of carcinoma with significant clinical implications. PMID- 22669749 TI - Therapeutic attenuation of neuroinflammation and apoptosis by black tea theaflavin in chronic MPTP/probenecid model of Parkinson's disease. AB - Neuroinflammation and apoptosis in the dopaminergic neurons of substantia nigra play an important role in the pathogenesis of experimental and clinical Parkinson's disease (PD). This study focused on the possible anti-inflammatory and anti-apoptotic effects of theaflavin (TF), a black tea polyphenol against 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in mice. C57BL/6 male mice were treated with 10 doses of MPTP (25 mg/kg, s.c.) and probenecid (250 mg/kg, i.p.) for 3.5 days interval. TF (10 mg/kg) was administered 1 h prior to the administration of MPTP for 35 days of experimental period. MPTP/p treatment upregulates the release of interleukin-1beta, IL-6, tumor necrosis factor-alpha, IL-10, glial fibrillary acidic protein and Bax, and downregulates anti-apoptotic marker Bcl-2. Oral treatment of black tea polyphenol TF significantly attenuates MPTP-induced neuroinflammation as well as apoptosis. Behavioral studies (catalepsy and akinesia) were carried out to confirm these molecular studies. The results demonstrate that TF mediated its neuroprotection against chronic MPTP-induced toxicity through the involvement of multiple molecular events. It was concluded that TF may provide a precious therapeutic strategy for the treatment of progressive neurodegenerative disease such as PD in future. PMID- 22669748 TI - Oxidative damage to RNA in aging and neurodegenerative disorders. AB - An age-associated increase in oxidative damage to nucleic acids, predominantly to RNA, has been recently demonstrated in neurons of human and rodent brains, which may play a fundamental role in the development of age-associated neurodegeneration. Indeed, more prominent levels of neuronal RNA oxidation compared to normal aging have been described in neurodegenerative disorders including Alzheimer disease, Parkinson disease, dementia with Lewy bodies, and amyotrophic lateral sclerosis. Moreover, oxidative damage to RNA has been found also in cellular and animal model of neurodegeneration. Oxidative RNA modification can occur not only in protein-coding RNAs but also in non-coding RNAs that are recently revealed to contribute towards the complexity of the mammalian brain. It has been hypothesized that RNA oxidation causes aberrant expression of microRNAs and proteins and subsequently initiates inappropriate cell fate pathways. While less lethal than mutations in the genome and not inheritable, such sublethal damage to cells might be associated with underlying mechanisms of degeneration, especially age-associated neurodegeneration. Of particular interest, the accumulating evidence obtained from studies on either human samples or experimental models coincidentally suggests that RNA oxidation is a feature in neurons of aging brain and more prominently observed in vulnerable neurons at early-stage of age-associated neurodegenerative disorders, indicating that RNA oxidation actively contributes to the background, the onset, and the development of the disorders. Further investigations aimed at understanding of the processing mechanisms related to oxidative RNA damage and its consequences may provide significant insights into the pathogenesis of neurodegenerative disorders and lead to better therapeutic strategies. PMID- 22669750 TI - Response of hippocampal neurons and glial cells to alternating magnetic field in gerbils submitted to global cerebral ischemia. AB - The purpose of this study was to determine whether exposure to an extremely low frequency magnetic field (ELF-MF, 50 Hz) affects the outcome of postischemic damage in the hippocampus of Mongolian gerbils. After 10-min bilateral carotid occlusion, the gerbils were continuously exposed to ELF-MF (average magnetic induction at the center of the cage was 0.5 mT) for 7 days. The impact of ELF-MF was estimated immediately (the 7th day after reperfusion) and 7 days after cessation of exposure (the 14th day after reperfusion) compared with ischemic gerbils without ELF-MF exposure. Applying stereological methods, histological evaluation of changes in the hippocampus was done for determining its volume, volume densities of degenerating neurons and astrocytes, as well as the number of microglial cells per unit area. ELF-MF per se did not induce any morphological changes, while 10-min global cerebral ischemia led to neuronal death, especially in CA1 region of the hippocampus, as expected. Ischemic gerbils exposed to ELF-MF had significantly a lower degree of cell loss in the examined structure and greater responses of astrocytes and microglial cells than postischemic gerbils without exposure on the seventh day after reperfusion (immediate effect of ELF MF). Similar response was observed on the 14th day after reperfusion (delayed effect of ELF-MF); however, differences in measured parameters were low and insignificant. Applied ELF-MF has possible neuroprotective function in the hippocampus, as the most sensitive brain structure in the model of global cerebral ischemia, through reduction of neuronal death and activation of astrocytes and microglial cells. PMID- 22669751 TI - N-TproBNP as biomarker in systemic sclerosis. AB - Systemic sclerosis (SSc) is a connective tissue disorder characterized by tissue fibrosis affecting the skin and internal organs, fibroproliferative vasculopathy, and autoimmune activation. SSc still heralds a poor prognosis with significant morbidity and mortality. Early detection of organ involvement is critical as currently available treatments are most effective when started early. Many candidate biomarkers have been investigated in the past two decades. However, despite the enormous efforts, no accurate tool to predict the pattern of organ involvement and to assess disease activity has been yet identified. The N terminal fragment of probrain natriuretic peptide (N-TproBNP) is a neurohormone released by ventricular myocytes in response to pressure overload. N-TproBNP is highly relevant for diagnosis, prognosis, and prediction of pulmonary arterial hypertension in SSc. Moreover, several studies support its potential benefit for cardiac assessment of scleroderma patients. Conversely, the role of N-TproBNP as surrogate marker of pulmonary fibrosis and skin involvement is much less clear. We provide an extensive review of the studies that have previously investigated the role of N-TproBNP as candidate biomarker in scleroderma manifestations, presenting also the findings of a recent study we conducted in a cohort of 87 SSc patients. PMID- 22669752 TI - Integrative medicine in allergy and immunology. AB - Integrative medicine is a relatively new discipline which attempts to combine allopathic medicine with alternative or complementary medicine, to reap the benefits of both forms of medicine in optimizing the care of patients. Integrative medicine concentrates on treating the patient as a whole, both in body and mind. While the scientific method and "evidence-based" clinical research drives the management and treatment of diseases in conventional Western medicine, alternative or complementary medicine is based on unproven yet potentially beneficial techniques that have been developed throughout history, dating back to the ancient cultures in the Middle East, Africa, and China. In spite of the lack of evidence of most alternative medicine techniques, these methodologies have been practiced for centuries with great acceptance in many countries. It is in the Western world, where "modern" medicine is dictated by the scientific method, that the most controversy in the use of these alternative modes of therapy exists. Since the science behind alternative medicine is incomplete or non existent, it is difficult for those trained in Western medicine to accept or adopt this approach. But perhaps it is the failure of Western medicine to adequately guarantee our well being and good health that have led to the ongoing debate between the medical profession and the general public as to the benefits of these alternative treatments. In one sense, integrative medicine may be a futile attempt to coin a new term in the hope of legitimizing alternative medicine. On the other hand, there is a wealth of historical experience in the use of the techniques. Studies to evaluate the scientific basis behind ancient medical techniques are ongoing, and it is to be expected that the results will neither be uniformly positive nor negative. Of particular interest is the effect of traditional medicine, herbal formulations, and manipulative techniques on the immune system, and its application in the treatment of autoimmune and allergic diseases. Studies are being designed or conducted to investigate immune effects of herbal formulations or their components. Herbal plants or medicines may lead to skewing of the Th1/Th2 balance in either direction, thus may offer potential application in the treatment of allergic or autoimmune diseases. PMID- 22669754 TI - Antineutrophil cytoplasmic autoantibodies: how are they detected and what is their use for diagnosis, classification and follow-up? AB - Antineutrophil cytoplasmic antibodies (ANCA) are traditionally detected by an indirect immunofluorescence technique. According to the international consensus on ANCA testing, ANCA should also be tested by antigen-specific tests for myeloperoxidase-ANCA and proteinase 3-ANCA. The direct noncompetitive enzyme linked immunosorbent assay (ELISA) used to be the method of choice. Nowadays, these assays are called "first-generation" assays. Second-generation tests (capture ELISA) or third-generation tests (anchor ELISA) are more sensitive and specific for ANCA testing. We postulate that ANCA as detected by these newer ANCA tests may replace the need to perform indirect immunofluorescence-based assays. For classification of patients, ANCA serotype seems more important than classifying patients according to their clinical subtype, since genetics, clinical manifestations and response to therapy are more related to ANCA serotype than to clinical subtype. Detection of ANCA to monitor disease activity is still a controversial issue. Treatment based on ANCA levels is at present only experimentally performed in those patients who are treated with B-cell depletion therapy with rituximab. Future studies are needed to establish whether this way of monitoring patients is warranted. PMID- 22669753 TI - Recurrent miscarriage, antiphospholipid antibodies and the risk of thromboembolic disease. AB - Miscarriage affects 15 % of women, and while most are sporadic, there is a subset comprising 2-5 % of couples that suffers recurrent miscarriage (RM). Much work has been carried out to try to identify the RM underlying mechanisms. A subgroup of women with RM has been demonstrated to be in a prothrombotic state before pregnancy. The long-term health implications of this hypercoagulability may imply an increased risk of thrombotic events, including ischemic heart disease. Moreover, the presence of antiphospholipid antibodies (aPL), rather than thrombophilic genetic defects (i.e., factor V Leiden or prothrombin G202010A mutation) in patients with RM, is a determinant of thrombotic events later in life, especially among those patients having also classic cardiovascular risk factors. These facts may have therapeutic implications. The efficacy of long-term thromboprophylaxis and its associated risk of bleeding is a complex problem in aPL-positive patients who have not developed previous thrombosis or in patients with antiphospholipid syndrome with isolated obstetric morbidity (i.e., RM). While most authors advocate the use of antithrombotic therapy only in patients with aPL and thromboembolic events, there is no consensus as to whether patients who have not experienced yet any thrombotic event might also be given prophylaxis. Low-dose aspirin may be effective in the prevention of thrombosis for asymptomatic, persistently aPL-positive individuals who have additional thrombosis risk factors, i.e., hypertension and lupus anticoagulant have been found to be independent risk factors for thrombosis in aPL carriers, and therefore, the use of thromboprophylaxis in these high-risk subjects could be recommend. PMID- 22669755 TI - Treatment of ANCA-associated vasculitis, where to go? AB - The introduction of (oral) cyclophosphamide (CYC) in the treatment of ANCA associated vasculitides (AAV) has strongly improved prognosis but the side effects of long-term CYC treatment are serious. A number of recent randomized controlled studies have shown that the cumulative dose of CYC can be strongly reduced in the treatment of AAV or even reduced to zero. Maintenance treatment can be performed with azathioprine (AZA), or methotrexate (MTX) in case of intolerance, although the intensity and duration of maintenance treatment is still under discussion. More insight into the mechanisms involved in relapsing disease might allow individualized treatment. Induction of remission can be achieved in cases of mild disease expression with MTX but requires maintenance treatment to prevent relapses. Generalized disease can be treated with pulses of i.v. CYC or, possibly, with MMF. However, recent studies demonstrate the efficacy of RTX in inducing remission without the concomitant use of immunosuppressives. Corticosteroids are part of treatment in all regimens but the intensity and duration of steroid treatment is still being discussed. In life-threatening disease, the adjunctive efficacy of plasma exchange has been demonstrated and its usefulness in less severe disease is under investigation. Taken together, there are, indeed, alternatives for CYC in AAV. PMID- 22669756 TI - Considerations of traditional Chinese medicine as adjunct therapy in the management of ulcerative colitis. AB - Ulcerative colitis (UC) has been treated with traditional Chinese medicine (TCM) for literally thousands of years. This paper gives an overview of TCM in the management of UC, provides an account of the state of the evidence, identifies gaps in the research base, and makes recommendations for future research. TCM is based on patterns and this influences the selection of the type of herbal medication or manipulation technique used for treatment. The majority of clinical studies on the efficacy of Chinese herbal medicine and acupuncture in the treatment of UC have methodological shortcomings. The extent of heterogeneity in many of these clinical trials, poor design quality of past studies prevent meaningful systematic reviews (SRs) or meta-analysis, although there are positive signs that TCM may be useful in relieving abdominal pain and reducing inflammation. Many unknowns still exist, including the active ingredients within Chinese herbal medicine and the potential for interaction with other drugs or western medications. While there may be a potential role for utilizing TCM in the treatment of UC patients relying on both traditional concepts and modern developments, it should be recognized that there are no studies that irrefutably support the use of TCM in the treatment of UC. Further basic or translational research must be done to elucidate mechanisms of action of these agents, and well designed and well-conducted clinical studies must also be done to determine efficacy and safety of these agents. PMID- 22669757 TI - Quality standards for sample collection in coagulation testing. AB - Preanalytical activities, especially those directly connected with blood sample collection and handling, are the most vulnerable steps throughout the testing process. The receipt of unsuitable samples is commonplace in laboratory practice and represents a serious problem, given the reliability of test results can be adversely compromised following analysis of these specimens. The basic criteria for an appropriate and safe venipuncture are nearly identical to those used for collecting blood for clinical chemistry and immunochemistry testing, and entail proper patient identification, use of the correct technique, as well as appropriate devices and needles. There are, however, some peculiar aspects, which are deemed to be particularly critical when collecting quality specimens for clot based tests, and these require clearer recognition. These include prevention of prolonged venous stasis, collection of nonhemolyzed specimens, order of draw, and appropriate filling and mixing of the primary collection tubes. All of these important preanalytical issues are discussed in this article, and evidence-based suggestions as well as recommendations on how to obtain a high-quality sample for coagulation testing are also illustrated. We have also performed an investigation aimed to identify variation of test results due to underfilling of primary blood tubes, and have identified a clinically significant bias in test results when tubes are drawn at less than 89% of total fill for activated partial thromboplastin time, less than 78% for fibrinogen, and less than 67% for coagulation factor VIII, whereas prothrombin time and activated protein C resistance remain relatively reliable even in tubes drawn at 67% of the nominal volume. PMID- 22669758 TI - Critical moments in time: reflections on the development of orthogonal acceleration time-of-flight mass spectrometry. AB - This paper reflects on the historical development of orthogonal acceleration time of-flight analyzers that have been used routinely for high sensitivity analyses of biological molecules for more than a decade. In particular, the role of the late Michael Guilhaus from the University of New South Wales in Australia is highlighted. This account shows that like most advances in science, successful commercialization of new technology is not straightforward and is often the result of critical contributions of different people and organizations at different points in time. PMID- 22669759 TI - Automated precursor ion exclusion during LC-MS/MS data acquisition for optimal ion identification. AB - Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is widely used for characterizing multiple samples of complex mixtures with similar compositions. This article addresses a data acquisition strategy for collecting a maximal number of unique, high-quality MS/MS during LC-MS/MS analysis of multiple samples. Based on the concept that a component only needs to be identified once when analyzing multiple samples with similar compositions, an automated intersample data-dependent acquisition strategy was developed. The strategy is based on precursor ion exclusion (PIE) and is implemented in MassAnalyzer in an automated fashion for Thermo Scientific (San Jose, CA, USA) mass spectrometers. In this method, MassAnalyzer submits one sample at a time to the sample queue. After data acquisition of each sample, MassAnalyzer automatically analyzes the data to generate a PIE list based on the MS/MS precursor ions, merges this list with the list generated from previous runs, adds the list to the MS method file, and submits the next sample to the queue. The PIE list contains both m/z value and time window for each precursor ion, and is generated intelligently so that if an MS/MS is insufficient for identifying the peak of interest, it will be collected again near the top of the peak in the next run. Therefore, the strategy maximizes both quality and the number of unique MS/MS. When automated PIE was used to acquire LC-MS/MS data of an antibody tryptic digest and a soy hydrolysate sample, the number of identified ions increased by 52% and 93%, respectively, compared with data acquired without using PIE. PMID- 22669760 TI - New protein footprinting: fast photochemical iodination combined with top-down and bottom-up mass spectrometry. AB - We report a new approach for the fast photochemical oxidation of proteins (FPOP) whereby iodine species are used as the modifying reagent. We generate the radicals by photolysis of iodobenzoic acid at 248 nm; the putative iodine radical then rapidly modifies the target protein. This iodine-radical labeling is sensitive, tunable, and site-specific, modifying only histidine and tyrosine residues in contrast to OH radicals that modify 14 amino-acid side chains. We iodinated myoglobin (Mb) and apomyoglobin (aMb) in their native states and analyzed the outcome by both top-down and bottom-up proteomic strategies. Top down sequencing selects a certain level (addition of one I, two I's) of modification and determines the major components produced in the modification reaction, whereas bottom-up reveals details for each modification site. Tyr146 is found to be modified for aMb but less so for Mb. His82, His93, and His97 are at least 10 times more modified for aMb than for Mb, in agreement with NMR studies. For carbonic anhydrase and its apo form, there are no significant differences of the modification extents, indicating their similarity in conformation and providing a control for this approach. For lispro insulin, insulin-EDTA, and insulin complexed with zinc, iodination yields are sensitive to differences in insulin oligomerization state. The iodine radical labeling is a promising addition to protein footprinting methods, offering higher specificity and lower reactivity than ?OH and SO(4)(-?), two other radicals already employed in FPOP. PMID- 22669761 TI - Cascade dissociations of peptide cation-radicals. Part 1. Scope and effects of amino acid residues in penta-, nona-, and decapeptides. AB - Amino acid residue-specific backbone and side-chain dissociations of peptide z ions in MS(3) spectra were elucidated for over 40 pentapeptides with arginine C terminated sequences of the AAXAR and AAHXR type, nonapeptides of the AAHAAXX"AR and AAHAXAX"AR type, and AAHAAXX"AAR decapeptides. Peptide z(n) ions containing amino acid residues with readily transferrable benzylic or tertiary beta-hydrogen atoms (Phe, Tyr, His, Trp, Val) underwent facile backbone cleavages to form dominant z(n-2) or z(n-3) ions. These backbone cleavages are thought to be triggered by a side-chain beta-hydrogen atom transfer to the z ion C(alpha) radical site followed by homolytic dissociation of the adjacent C(alpha)-CO bond, forming x(n-2) cation-radicals that spontaneously dissociate by loss of HNCO. Amino acid residues that do not have readily transferrable beta-hydrogen atoms (Gly, Ala) do not undergo the z(n) -> z(n-2) dissociations. The backbone cleavages compete with side-chain dissociations in z ions containing Asp and Asn residues. Side-chain dissociations are thought to be triggered by alpha-hydrogen atom transfers that activate the C(beta)-C(gamma) or C(beta)-heteroatom bonds for dissociations that dominate the MS(3) spectra of z ions from peptides containing Leu, Cys, Lys, Met, Ser, Arg, Glu, and Gln residues. The Lys, Arg, Gln, and Glu residues also participate in gamma-hydrogen atom transfers that trigger other side-chain dissociations. PMID- 22669762 TI - Cascade dissociations of peptide cation-radicals. Part 2. Infrared multiphoton dissociation and mechanistic studies of z-ions from pentapeptides. AB - Dissociations of z(4) ions from pentapeptides AAXAR where X=H, Y, F, W, and V produce dominant z(2) ions that account for >50 % of the fragment ion intensity. The dissociation has been studied in detail by experiment and theory and found to involve several isomerization and bond-breaking steps. Isomerizations in z(4) ions proceed by amide trans->cis rotations followed by radical-induced transfer of a beta-hydrogen atom from the side chain, forming stable C(beta) radical intermediates. These undergo rate-determining cleavage of the C(alpha)-CO bond at the X residue followed by loss of the neutral AX fragment, forming x(2) intermediates. The latter were detected by energy-resolved resonant excitation collision-induced dissociation (CID) and infrared multiphoton dissociation (IRMPD) experiments. The x(2) intermediates undergo facile loss of HNCO to form z(2) fragment ions, as also confirmed by energy-resolved CID and IRMPD MS(4) experiments. The loss of HNCO from the x(2) ion from AAHWR is kinetically hampered by the Trp residue that traps the OCNH radical group in a cyclic intermediate. PMID- 22669763 TI - Time to face the fats: what can mass spectrometry reveal about the structure of lipids and their interactions with proteins? AB - Since the 1950s, X-ray crystallography has been the mainstay of structural biology, providing detailed atomic-level structures that continue to revolutionize our understanding of protein function. From recent advances in this discipline, a picture has emerged of intimate and specific interactions between lipids and proteins that has driven renewed interest in the structure of lipids themselves and raised intriguing questions as to the specificity and stoichiometry in lipid-protein complexes. Herein we demonstrate some of the limitations of crystallography in resolving critical structural features of ligated lipids and thus determining how these motifs impact protein binding. As a consequence, mass spectrometry must play an important and complementary role in unraveling the complexities of lipid-protein interactions. We evaluate recent advances and highlight ongoing challenges towards the twin goals of (1) complete structure elucidation of low, abundant, and structurally diverse lipids by mass spectrometry alone, and (2) assignment of stoichiometry and specificity of lipid interactions within protein complexes. PMID- 22669765 TI - Look beyond the red eyes! AB - This is a case of a 63-year-old gentleman who presented with persistent red eyes to the eye clinic for several months. He had been seen in the eye department on several visits when he was noted to have red ears too. This led to further review in the rheumatology and ear, nose and throat clinic to confirm the diagnosis of relapsing polychondritis. He was treated successfully with systemic steroids. PMID- 22669766 TI - Sudden loss of vision in a patient with significant ipsilateral internal carotid disease. AB - A 74-year-old man developed sudden onset of painless persistent partial loss of vision in the right eye 3 days after right total knee replacement. The initial investigation was for amaurosis fugax with a normal CT scan of the brain but the carotid Doppler confirmed >90% stenosis of the right internal carotid artery. Urgent ophthalmological review confirmed anterior ischaemic optic neuropathy. Subsequently, he lost his vision completely in the right eye. He had a previous high risk hemispheric transient ischaemic attack with carotid Doppler reported as normal. PMID- 22669764 TI - Ligand binding promotes CDK-dependent phosphorylation of ER-alpha on hinge serine 294 but inhibits ligand-independent phosphorylation of serine 305. AB - Phosphorylation of estrogen receptor-alpha (ERalpha) is critical for its transcription factor activity and may determine its predictive and therapeutic value as a biomarker for ERalpha-positive breast cancers. Recent attention has turned to the poorly understood ERalpha hinge domain, as phosphorylation at serine 305 (Ser305) associates with poor clinical outcome and endocrine resistance. We show that phosphorylation of a neighboring hinge domain site, Ser294, analyzed by multiple reaction monitoring mass spectrometry of ERalpha immunoprecipitates from human breast cancer cells is robustly phosphorylated exclusively by ligand (estradiol and tamoxifen) activation of ERalpha and not by growth factor stimulation (EGF, insulin, heregulin-beta). In a reciprocal fashion, Ser305 phosphorylation is induced by growth factors but not ligand activation of ERalpha. Phosphorylation at Ser294 and Ser305 is suppressed upon co stimulation by EGF and ligand, respectively, unlike the N-terminal (AF-1) domain Ser118 and Ser167 sites of ERalpha where phosphorylation is enhanced by ligand and growth factor co-stimulation. Inhibition of cyclin-dependent kinases (CDK) by roscovitine or SNS-032 suppresses ligand-activated Ser294 phosphorylation without affecting Ser118 or Ser104/Ser106 phosphorylation. Likewise, cell-free studies using recombinant ERalpha and specific cyclin-CDK complexes suggest that Ser294 phosphorylation is primarily induced by the transcription-regulating and cell cycle-independent kinase CDK7. Thus, CDK-dependent phosphorylation at Ser294 differentiates ligand-dependent from ligand-independent activation of Ser305 phosphorylation, showing that hinge domain phosphorylation patterns uniquely inform on the various ERalpha activation mechanisms thought to underlie the biologic and clinical diversity of hormone-dependent breast cancers. PMID- 22669767 TI - A large swelling of the tongue. AB - Hyalinising clear cell carcinoma (HCCC) is an infrequent distinct histological subtype of clear cell adenocarcinoma encountered in minor salivary glands which can be confused with a variety of clear cell-rich tumours. The entity of HCCC should be considered in patients presenting with well-circumscribed longstanding nodular enlargement without any other significant abnormality. HCCC is often difficult to diagnose due to its unusual presentation. This report presents a male patient who reported with a complaint of 2 month history of a large swelling on the tongue. The clinical, radiological, histological and immunohistochemical findings, confirmed the diagnosis of HCCC. PMID- 22669768 TI - Osteoid osteoma of mandible. AB - Osteomas are benign, slow-growing osteogenic tumours rarely occurring in the craniofacial bones. Osteomas are characterised by the proliferation of compact and/or cancellous bone. It can be of a central, peripheral, or extra skeletal type. The peripheral type arises from the periosteum and is rarely seen in the mandible. The lingual surface and lower border of the body are the most common locations of these lesions. They are usually asymptomatic and can be discovered in routine clinical and radiographic examination. In this paper, the authors present a large solitary peripheral osteoma located in the inferior surface of the left angle of mandible and causing facial deformity in a 14-year-old boy. Radiographic examination by diagnostic radiographs revealed mixed appearance (radiopaque- radiolucent), well-circumscribed, pedunculated mass approximately 3.5 cm in size. The osteoma was removed surgically, and no recurrence has been observed. PMID- 22669769 TI - A fixation of the right humerus to the iliac crest. AB - A patient with a shattered Gustilo 3B floating shoulder with an intact neurovascular bundle and a reasonably functional hand was encountered in Sri Lanka, following a blast injury. The limb was salvaged by using an external fixator to fix the humerus to the ipsilateral iliac crest. The wound healed well rendering the patient with a limp shoulder but, a functional hand which she could use by supporting the elbow with the left hand. This technique can be an option in rare situations such as the case in discussion to salvage 'floating shoulders' without disarticulation. PMID- 22669770 TI - An interesting case that included visual hallucinations in a patient with severe hypomagnesaemia and hypocalcaemia. AB - A 57-year-old man presenting with profound visual hallucinations was found to have severe hypomagnesaemia and hypocalcaemia with a normal level of parathyroid hormone (PTH). Magnesium is essential to the release of PTH so the suspected pathophysiology was thought to be: low Mg -> inappropriately low PTH -> low Ca. He commenced supplementation and his symptoms resolved. Causes of hypomagnesaemia are discussed. PMID- 22669771 TI - An unusual cause of miliary radiographic pattern. PMID- 22669772 TI - Coeliac disease presenting as chronic cough in an 8-year-old child. AB - Patients with the 'classical' gastrointestinal symptoms of coeliac disease (CD) are usually readily diagnosed and treated with a gluten exclusion diet. However, the advent of sensitive serological investigations has revealed that over half of childhood CD remains asymptomatic or presents with more subtle non gastrointestinal symptoms, with a significant risk to the health of undiagnosed children. In view of its changing presentation there is an increasing need for clinicians to have a low threshold to investigate patients for this disease. Rare cases of CD associated with respiratory symptoms have been reported. The authors report an interesting case presenting as chronic cough in an otherwise asymptomatic 8-year-old girl. As a result of having a low threshold of suspicion for underlying CD, a diagnosis has been made and the long-term health risks of undiagnosed disease have been improved in both the patient and her immediate family. PMID- 22669773 TI - Ileo-colic intussusception in premature neonate. AB - Intussusception in neonatal age is very rare. A 12-day-old child was referred from peripheral hospital with history of intolerance to feed, absolute constipation, abdominal distension and significant bilious aspirate. Per-rectal examination revealed necrotic haemorrhagic fluid. The patient was treated on the lines of necrotising enterocolitis in the referring hospital. On further investigation and exploration, the patient turned out to be ileo-colic intussusception which is exceedingly less common in premature neonates. Hence, other causes of intestinal obstruction should also be considered along with vigilant clinical outlook in neonates. PMID- 22669774 TI - The efficacy of cinacalcet combined with conventional therapy on bone and mineral metabolism in dialysis patients with secondary hyperparathyroidism: a meta analysis. AB - Cinacalcet, the first calcimimetic to be approved for the treatment of secondary hyperparathyroidism (SHPT) in the chronic kidney disease patients, offers a novel therapeutic approach to SHPT. The aim of this meta-analysis is to access the efficacy and safety of cinacalcet on bone and mineral metabolism disorders in the dialysis patients with SHPT. Randomized controlled trials on cinacalcet combined with vitamin D and/or phosphate binders in the dialysis patients with SHPT were identified in Pubmed, Sciencedirect, and the Cochrane library. Data were analyzed with RevMan software. We compared the proportion of patients achieving the biochemical targets recommended by the Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines and the incidence of adverse events between the cinacalcet and control groups. Six trials involving 2,548 patients were included. A greater proportion of patients in the cinacalcet group compared with the conventional group achieved the KDOQI targets. The relative risks (RRs) were parathyroid hormone (PTH) (RR = 3.51, 95 % CI: 2.38-5.17), calcium (RR = 2.04, 95 % CI: 1.76 2.37), phosphorus (RR = 1.15, 95 % CI: 0.83-1.60), and calcium-phosphorus product (Ca * P) (RR = 1.41, 95 % CI: 1.18-1.69), the number of patients simultaneously achieving the KDOQI targets for PTH + Ca * P was also greater (RR = 3.89, 95 % CI: 2.36-6.41), with p < 0.001 for each. The most common adverse events were nausea, vomiting, diarrhea, and hypocalcemia, which had a higher incidence in the cinacalcet group, but were usually mild to moderate in severity and transient. Compared with conventional therapy, treatment with cinacalcet results in more patients achieving KDOQI targets and offers an effective and safety therapeutic option for controlling mineral and bone disorders in the dialysis patients with SHPT. PMID- 22669775 TI - MMP2 expression is a prognostic marker for primary melanoma patients. AB - BACKGROUND: Matrix metalloproteinase 2 (MMP2) is a collagenase, which aids tumor growth and invasion by digesting the extracellular matrix surrounding the tumor tissue. Our study examined MMP2 expression in various stages of melanoma progression and tested the prognostic significance of MMP2 expression. We also analyzed the correlation between p-Akt status and MMP2 expression in melanoma patients. METHODS: Tissue microarray (TMA) and immunohistochemistry were employed to study the expression of MMP2. A total of 482 melanoma (330 primary and 152 metastatic) tumor biopsies and 149 nevi biopsies (49 normal and 100 dysplastic nevi) were used for the analysis. MMP2 expression was correlated with melanoma progression. Kaplan-Meier survival curve and multivariate Cox regression analysis were applied to verify the prognostic significance of MMP2 expression. The correlation between MMP2 and p-Akt expression was analyzed in 92 cases which were common in the present and the previous study on p-Akt expression. RESULTS: Strong MMP2 expression is significantly increased in primary (25 %) and metastatic melanoma (43 %) compared to normal (5 %) and dysplastic nevi (10 %). Patients with strong MMP2 had significantly poorer survival compared to those with negative-to-moderate MMP2 expression. MMP2 expression could predict the patient survival independent of tumor thickness and ulceration. Furthermore, in our cohort study MMP2 expression was associated with p-Akt status and patient survival. CONCLUSIONS: Strong MMP2 staining is associated with worse survival of melanoma patients and is an independent molecular prognostic factor for primary melanoma. PMID- 22669777 TI - [Puncture of ascites: abdominal paracentesis]. PMID- 22669776 TI - Discovery of TP53 splice variants in two novel papillary urothelial cancer cell lines. AB - BACKGROUND: Using a novel cell culture technique, we established two new cell lines, BC44 and BC61, from papillary urothelial carcinoma and analyzed them for genetic changes typical of this tumor type. METHODS AND RESULTS: Karyotyping revealed aneuploid karyotypes with loss of chromosome 9 and rearranged chromosome 5p. Molecular analysis showed CDKN2A deletions but wild-type PIK3CA. BC61 contained a G372C FGFR3 mutation. TP53 was not mutated in either cell line and BC61 expressed normal full-length protein. In contrast, BC44 exclusively expressed cytoplasmic and nuclear p53Delta40 and 133 isoforms from the alternative promoter P2 as revealed by Western blotting, immunocytochemistry and PCR. The only discernible difference in TP53 in BC44 was homozygosity for the deletion allele of the rs17878362 polymorphism in the P2 promoter. Expression of p53 isoforms was also detected in a few other urothelial carcinoma cell lines and tumor cultures and in 4 out of 28 carcinoma tissues. CONCLUSION: In urothelial cancers, TP53 is typically inactivated by mutations in one allele and loss of the wildtype allele and more frequently in invasive compared to papillary carcinomas. We show that some urothelial carcinomas may predominantly or exclusively express isoforms which are not detected by commonly used antibodies to epitopes located in the p53 TA amino-terminal region. Expression of these isoforms may constitute a further mode of p53 inactivation in urothelial carcinoma. Our findings raise the question to which extent this mechanism may compromise wildtype p53 function in papillary tumors in particular, where point mutations in the gene are rare. PMID- 22669778 TI - [What is your diagnosis? Mycoplasma pneumoniae pneumonia]. PMID- 22669779 TI - [The neurosurgical therapy of trigeminal neuralgia]. AB - The Trigeminal Neuralgie (TN) is he most common cause of facial pain with an incidence of 27 per 100'000 patients per year. The symptoms are paroxysmal stabbing, tearing, and burning pain usually in the area of the second and third trigeminal nerve, that can be provoked by drinking, shaving, chewing or talking. If the classical drug therapy with anticonvulsants is not sufficient or must be discontinued due to side effects, then the retrosigmoidal craniotomy and micro vascular decompression in vascular-nerve-contact ot partial rhizotomy are good pain-free procedures. Such operations are of low risk in the hands of experienced neurosurgeons and possible to be carried out even in elderly patients. A high percentage of free of complaints postoperative and low recurrence rate legitimate this method. PMID- 22669780 TI - [Effect of paracetamol (acetaminophen) on blood pressure in patients with coronary heart disease]. AB - Analgesic drugs, non-steroidal anti-inflammatory drugs and paracetamol (acetaminophen) in particular, belong to the most widely prescribed therapeutic agents. Beside their efficacy in pain relief, these drugs were recently linked to increased cardiovascular risk. Indeed, epidemiological and clinical studies showed that non-selective non-steroidal anti-inflammatory drugs, as well as selective cyclooxygenase-2 inhibitors both may increase blood pressure and cardiovascular events. However, the effect of paracetamol (acetaminophen) on blood pressure and cardiovascular health should not be neglected, too. Unfortunately, long-term randomized controlled trials appropriately powered to evaluate cardiovascular outcomes are lacking. This review summarizes the available data about the effect of paracetamol in particular, on blood pressure and other cardiovascular outcomes. PMID- 22669781 TI - [Critical reflexion on quality improvement and networking]. AB - Qualitiy-control and networking are two issues of debate in modern medicine. The origin of these terms is not to be found in medicine, but rather in industry. However their naive transfer to the field of medicine causes damage. It is relatively easy to test industrial products for their quality. Dealing with meaningful medical problems is far too complex. Simple data such as blood pressure, HbA1c, etc. may be assessed. The only means of quality-control of complex medical situations and actions are ward rounds by attending physicians, case presentations at staff meetings, etc. Issues of clinical quality-control are discussed on the basis of the history of an aged couple. Furthermore a personal clinical experience illustrates how doctors create a useful network with other physicians and how they eliminate "useless" colleagues from their network. Economists should have no influence or impact whatsoever on the quality-control and networking of physicians. PMID- 22669782 TI - [Diagnosis of Helicobacter pylori infection]. PMID- 22669783 TI - [Consequences of an accidental aspiration of petroleum in a case of a fire eating man]. AB - Fire-eater's pneumonitis, caused by aspiration of petroleum, is an infrequent clinical problem in our region. It is an acute inflammatory response of the lungs to the accidental aspiration of hydrocarbons, as shown in our patient. Despite the severe initial clinical und radiological presentation, fire-eater's pneumonitis usually shows a favourable evolution with "restitutio ad integrum". Acute mortality rate is less than 1%. Fire-eater's lung is a medical emergency and needs medical support and surveillance. There is no good evidence that systemic cortico-steroids and antibiotics are effective in the treatment of hydrocarbon aspiration. Concerning chronic lung injury after fire-eater's pneumonitis, there are favorable results from short observational series. PMID- 22669784 TI - [Not Available]. PMID- 22669785 TI - [Not Available]. PMID- 22669787 TI - [Cough and weight loss - CME ultrasound diagnosis. Pulmonary tuberculosis]. PMID- 22669790 TI - Should age be considered when proposing decompressive hemicraniectomy in malignant stroke, and if so where is the limit? PMID- 22669791 TI - A comparison of two diffusion process models in accounting for payoff and stimulus frequency manipulations. AB - I analyzed response time and accuracy data from a numerosity discrimination experiment in which both stimulus frequency and payoff structure were manipulated. The numerosity discrimination encompassed responding either "low" or "high" to the number of asterisks in a 10 * 10 grid, on the basis of an experimenter-determined decision cutoff (fixed at 50). In the stimulus frequency condition, there were more low than high stimuli in some blocks and more high than low stimuli in other blocks. In the payoff condition, responses were rewarded such that the relative value of a stimulus mimicked the relative frequency of that stimulus in the previous manipulation. I modeled the data using two sequential-sampling models in which evidence was accumulated until either a "low" or a "high" decision criterion was reached and a response was initiated: a single-stage diffusion model framework and a two-stage diffusion model framework. In using these two frameworks, the goal was to examine their relative merits across stimulus frequency and payoff structure manipulations. I found that shifts in starting point in a single-stage diffusion framework and shifts in the initial drift rate in the two-stage model were able to account for the data. I also found, however, that these two shifts across the two models produced similar changes in the random walk that described the decision process. In conclusion, I found that the similarities in the descriptions of the decision processes make it difficult to choose between the two models and suggested that such a choice should consider model assumptions and parameter estimate interpretations. PMID- 22669792 TI - Cognitive pitfall! Videogame players are not immune to dual-task costs. AB - With modern technological advances, we often find ourselves dividing our attention between multiple tasks. While this may seem a productive way to live, our attentional capacity is limited, and this yields costs in one or more of the many tasks that we try to do. Some people believe that they are immune to the costs of multitasking and commonly engage in potentially dangerous behavior, such as driving while talking on the phone. But are some groups of individuals indeed immune to dual-task costs? This study examines whether avid action videogame players, who have been shown to have heightened attentional capacities, are particularly adept multitaskers. Participants completed three visually demanding experimental paradigms (a driving videogame, a multiple-object-tracking task, and a visual search), with and without answering unrelated questions via a speakerphone (i.e., with and without a dual-task component). All of the participants, videogame players and nonvideogame players alike, performed worse while engaging in the additional dual task for all three paradigms. This suggests that extensive videogame experience may not offer immunity from dual-task costs. PMID- 22669793 TI - Effects of expectations on loudness and loudness difference. AB - To determine how expectations affect loudness and loudness difference, in two experiments we induced some subjects to expect loud sounds (condition L), some to expect soft sounds (condition S), and others to have no particular expectations (control). In Experiment 1, all subjects estimated the loudnesses of the same set of three moderately loud 1-kHz tones. Estimates were greatest for subjects in condition S and smallest for subjects in condition L. Control subjects' estimates were intermediate but closer to those of condition S subjects. In Experiment 2, subjects estimated the difference in loudness for pairs of moderately loud 1-kHz tones. Again, estimates were smallest for condition L subjects; estimates were greatest for control subjects, and condition S subjects' estimates were closer to control estimates than to condition L estimates. This pattern of results is explainable by a combination of (1) Parducci's (1995) range-frequency theory and (2) a gain control mechanism in the auditory system under top-down governance (Schneider, Parker, & Murphy, 2011). PMID- 22669794 TI - Antimicrobial therapy for bloodstream infection due to methicillin-susceptible Staphylococcus aureus in an era of increasing methicillin resistance: opportunities for antimicrobial stewardship. PMID- 22669795 TI - Effect of sodium nitroprusside on the occurrence of atrial fibrillation after cardiothoracic surgery. AB - BACKGROUND: Postoperative atrial fibrillation (POAF) is a frequent complication following cardiothoracic surgery and is associated with an increase in morbidity, mortality, and cost. One small prospective study of patients undergoing isolated coronary artery bypass graft surgery has demonstrated a decrease in the risk of POAF with the use of sodium nitroprusside. OBJECTIVE: To determine whether there is an association between intraoperative sodium nitroprusside use and the incidence of POAF. METHODS: A retrospective cohort of 1025 patients aged 18 years and older who underwent any cardiac surgery between April 2007 and July 2010 was evaluated at Regional Hospital of Scranton. Patients with a history of atrial fibrillation, those who had undergone cardiothoracic surgery, or those undergoing surgical treatment for atrial fibrillation were excluded. The primary outcome was the odds of developing POAF given the utilization of sodium nitroprusside during cardiothoracic surgery. POAF was defined according to the Society of Thoracic Surgeons Adult Cardiac Surgery Database version 2.61 as a new onset of atrial fibrillation/flutter requiring treatment that was not present preoperatively. Data on use of intraoperative sodium nitroprusside were obtained from the pharmacy department's billing database. RESULTS: The final analysis included 699 patients; 473 received sodium nitroprusside. The incidence of POAF was 25.4% in the sodium nitroprusside group and 27.9% in the control group. Univariate analysis demonstrated no association of sodium nitroprusside with POAF (OR 0.880; 95% CI 0.615 to 1.257). Multivariate analysis also showed no significant difference in the odds of POAF with sodium nitroprusside (OR 0.827; 95% CI 0.565 to 1.210). Repeating the analysis in 276 propensity score-matched patients also failed to demonstrate any association (OR 0.774; 95% CI 0.454 to 1.319). CONCLUSIONS: There was no significant association between the use of sodium nitroprusside during cardiothoracic surgery and POAF. PMID- 22669796 TI - Use of cilostazol in percutaneous coronary interventions. AB - OBJECTIVE: To evaluate the addition of cilostazol to standard dual antiplatelet therapy (DAT) with aspirin and clopidogrel in patients receiving coronary stenting. DATA SOURCES: Relevant information was identified through a search of MEDLINE (1966-November 2011), International Pharmaceutical Abstracts (1960-2011), and Cochrane Databases (publications archived until November 2011) using the terms cilostazol, percutaneous coronary intervention, triple therapy, and antiplatelet agents. STUDY SELECTION AND DATA EXTRACTION: English-language prospective and retrospective studies, including registry data in adults, were eligible for inclusion if triple therapy with cilostazol was compared with DAT with aspirin and clopidogrel in patients undergoing percutaneous coronary intervention (PCI) with stenting. Article bibliographies were also reviewed. DATA SYNTHESIS: Cilostazol uniquely possesses antiproliferative properties in addition to its antiplatelet effects. Several prospective and retrospective clinical trials evaluated it as a third agent in standard antiplatelet regimens after PCI with both bare metal and drug-eluting stents. Both angiographic and clinical outcomes, including major adverse cardiac events (MACEs), have been improved with the addition of cilostazol to DAT in most trials, without increasing bleeding risk. Higher-risk patients, such as elderly individuals and patients with diabetes, long lesions, or small vessels, seem to benefit the most from triple therapy. Patients who are poor responders to clopidogrel also appear to benefit from the addition of cilostazol by improving platelet reactivity with standard DAT. CONCLUSIONS: Triple therapy with cilostazol has been shown to reduce MACEs by providing increased inhibition of platelet aggregation and reducing the rates of in-stent thrombosis compared to DAT without increasing the risk of bleeding complications. Further studies are needed to identify proper patient selection based on risk factors for the addition of cilostazol. Additionally, studies comparing cilostazol with newer antiplatelet therapies, such as prasugrel and ticagrelor, are needed. PMID- 22669797 TI - Curriculum and instructional methods for drug information, literature evaluation, and biostatistics: survey of US pharmacy schools. AB - BACKGROUND: The drug information curriculum in US colleges of pharmacy continues to evolve. The American College of Clinical Pharmacy (ACCP) Drug Information Practice and Research Network (DI PRN) published an opinion paper with specific recommendations regarding drug information education in 2009. Adoption of these recommendations has not been evaluated. OBJECTIVE: To assess which recommendations made in the ACCP DI PRN opinion paper are included in US pharmacy school curricula and characterize faculty qualifications, educational methods, and recent changes in drug information education. METHODS: An electronic survey was designed using the ACCP DI PRN opinion paper and the Accreditation Council for Pharmacy Education standards and guidelines for accreditation of PharmD programs in the US. Survey questions addressed curricular content within the following categories: drug information, literature evaluation, and biostatistics. A letter including the online survey link was sent via email to the dean of each US college/school of pharmacy (N = 128). Recipients were instructed to forward the email to the individual at their institution who was the most knowledgeable about the content and methodology used for didactic drug information education. RESULTS: Sixty-four responses were included in the final analysis. Of the 19 ACCP DI PRN minimum core concepts, 9 (47%) were included in curricula of all responding institutions; 14 of 19 (74%) were included in curricula for all but 1 institution. In contrast, 5 of 16 concepts (31%) were not formally taught by a number of institutions. Many respondents noted an increased focus on evidence based medicine, medication safety, and informatics. CONCLUSIONS: Although a survey of drug information curricula documented substantial inclusion of the essential concepts presented in the ACCP DI PRN opinion paper, room for improvement remains in drug information curricula in US colleges of pharmacy. PMID- 22669799 TI - Rectal bleeding and hemostatic disorders induced by dabigatran etexilate in 2 elderly patients. AB - OBJECTIVE: To report rectal bleeding associated with hemostatic disorders in 2 elderly patients treated with dabigatran etexilate. CASE SUMMARY: A 79-year-old woman (weight, 69 kg) was hospitalized in a gastroenterology unit for severe rectal bleeding. She had been treated for 2 months with dabigatran etexilate 110 mg twice daily for chronic atrial fibrillation. On admission, her creatinine clearance (CrCl) was 20.7 mL/min/1.73 m(2), prothrombin time (PT) less than 10% (reference range 70-130%), and international normalized ratio (INR) 14.5 (venous blood). Eleven days after admission, hematologic and renal function were normalized and rectal bleeding stopped. An 84-year-old man (weight, 71 kg) was admitted for rectal bleeding with acute renal failure and dehydration that began while he was treated with dabigatran etexilate 110 mg twice daily for atrial fibrillation. On admission, CrCl was 33.5 mL/min/1.73 m(2), PT 13%, and INR 7.53 (venous blood). Dabigatran etexilate was stopped on admission. At the end of the hospitalization, CrCl was 66.5 mL/min/1.73 m(2), PT 54%, and INR 1.53. In both cases, an objective causality assessment revealed that those adverse reactions were probably related to dabigatran etexilate. DISCUSSION: In these 2 cases of rectal bleeding during dabigatran etexilate therapy, coagulation monitoring showed elevated PT and INR; neither patient had been exposed to vitamin K antagonists. These cases indicate the importance of PT and INR monitoring when using dabigatran etexilate, mainly in patients with a high risk of overdose, such as elderly patients or those with renal function impairment. CONCLUSIONS: It is critical to identify and subsequently manage dabigatran etexilate toxicity because there is no specific antidote to reverse the drug's anticoagulant effects. PMID- 22669800 TI - Shortened interval between tetanus vaccines. AB - OBJECTIVE: To identify the minimum safe interval between tetanus-diphtheria (Td) and tetanus-diphtheria-acellular pertussis (Tdap) vaccines. DATA SOURCES: Literature was retrieved through a review of ImmunoFacts, the Centers for Disease Control and Prevention (CDC) Web site, MEDLINE (1966-February 2012) and International Pharmaceutical Abstracts (1970-February 2012) using the terms Tdap, Td, and interval. In addition, reference citations from publications identified were reviewed. STUDY SELECTION AND DATA EXTRACTION: All English-language articles identified from the data sources were evaluated. Studies addressing an interval of 2 years or less between Td and Tdap vaccines were included. DATA SYNTHESIS: Two observational noninferiority studies have evaluated the safety of an interval of 2 years or less. The first involved a school-based immunization program to compare the safety of a single dose of Tdap given 18 months to 9 years after a tetanus and diphtheria toxoid-containing vaccine versus an interval of 10 or more years. Injection site erythema and swelling were increased among participants with shortened intervals between vaccines; however, no serious adverse events, entire limb swelling, or Arthus-like reactions were reported. The second study involved health care workers who received Tdap during a pertussis outbreak with the objective to compare safety of intervals less than 2 years between prior tetanus vaccination and Tdap with intervals 2 years or more. Criteria for noninferiority were met overall between the 2 intervals in terms of moderate and severe injection site reactions. Fever was more common with the shortened interval, as was any redness or any swelling. No serious adverse events were reported among the group with an interval of less than 2 years between vaccine administration. CONCLUSIONS: Although well-designed randomized controlled trials are lacking, the current observational evidence and CDC provisional recommendations support a shortened interval between Td and Tdap vaccines to protect health care workers from pertussis. Intervals less than 2 years may be associated with an increased incidence of local injection site reactions. PMID- 22669801 TI - Safety of mineralocorticoid receptor antagonists in patients receiving hemodialysis. AB - OBJECTIVE: To evaluate the literature supporting the safe use of mineralocorticoid antagonists (MRAs) in patients with end-stage renal disease who are receiving hemodialysis. DATA SOURCES: A review of the literature was performed using MEDLINE (1950 through week 2 of February 2012) using the key words and MeSH terms mineralocorticoid antagonists, aldosterone antagonists, spironolactone, or eplerenone combined with dialysis, renal disease, or kidney disease. STUDY SELECTION AND DATA EXTRACTION: Studies eligible for inclusion evaluated the impact of MRAs on serum potassium levels in patients with end-stage renal disease receiving hemodialysis. Data related to the patient populations and outcomes of interest were extracted from each publication. DATA SYNTHESIS: Ten studies were included in this review (spironolactone, 9; eplerenone, 1) and reported on the impact of MRAs on potassium levels in this population. In aggregate, the studies, with spironolactone doses ranging from 25 mg 3 times/week after dialysis to 300 mg/day and eplerenone doses of 25 mg twice daily, have shown little increases in serum potassium, particularly with the lower doses. The overall incidence of severe hyperkalemia was low. The literature base is limited by significant methodologic weaknesses of the studies, including low patient numbers, short follow-up periods, and lack of a blinded control group. CONCLUSIONS: The current literature suggests that MRAs may be used safely in patients with end-stage renal disease receiving hemodialysis, although additional large controlled trials are needed before definitive treatment recommendations can be made. PMID- 22669802 TI - Systematic review of consistency between adherence to cardiovascular or diabetes medication and health literacy in older adults. AB - OBJECTIVE: To review the relationship between health literacy and adherence to cardiovascular/diabetes medication. DATA SOURCES: We searched EMBASE (1974 February 2012) and MEDLINE (1948-February 2012). Search terms included health literacy, numeracy, health education and related terms, health literacy measurement tools, and medication adherence. STUDY SELECTION AND DATA EXTRACTION: English-language articles of all study designs were considered. Articles were included if they had a measurement of health literacy and medication adherence and if participants were older adults taking drugs for cardiovascular illness or diabetes mellitus. DATA SYNTHESIS: A total of 1310 citations were reviewed, including 9 articles that reported on 7 research studies. Most studies were retrospective, and all were based in the US. Because there was considerable diversity in measurements, participant characteristics, and outcome measures, we conducted a narrative synthesis rather than a meta-analysis. In assessing study validity, we looked at participant selection, method of measuring health literacy and medication adherence, missing data or losses, and adjustment for confounders. Of the 7 included studies, only 1 found a demonstrable association between health literacy and refill adherence. One clinical trial failed to show significant improvements in medication adherence after an intervention to improve health literacy. CONCLUSIONS: The current evidence does not show a definite association between health literacy and medication adherence in older adults with cardiovascular disease or diabetes mellitus. In the absence of a definite link, efforts to develop interventions to improve health literacy would not necessarily improve adherence to cardiovascular medications. There is an urgent need for robust studies outside of the US, with wider, generalized recruitment of participants. PMID- 22669803 TI - Review of the safety and efficacy of exenatide once weekly for the treatment of type 2 diabetes mellitus. AB - OBJECTIVE: To summarize and evaluate the available literature assessing the efficacy and safety of exenatide once weekly for the treatment of type 2 diabetes mellitus. DATA SOURCES: PubMed (1966-January 2012) and International Pharmaceutical Abstracts (1969-January 2012) were searched using the term exenatide once weekly. Abstracts presented at the European Association for the Study of Diabetes Annual Meeting in 2011 and reference citations from publications were reviewed for inclusion. Eli Lilly and Company and Amylin Pharmaceuticals were contacted for additional unpublished information. STUDY SELECTION AND DATA EXTRACTION: All English-language articles and abstracts were evaluated for inclusion. All randomized controlled trials were included in the review. DATA SYNTHESIS: The efficacy and safety of exenatide once weekly has been evaluated as initial monotherapy and as add-on therapy to metformin, sulfonylureas, and thiazolidinediones in patients with uncontrolled type 2 diabetes for up to 3 years. Results from 6 randomized, comparator-controlled studies in over 3000 patients indicate that treatment with exenatide once weekly results in significant glycemic improvements and weight loss. Gastrointestinal adverse effects and injection site reactions are common, but rarely lead to drug discontinuation. CONCLUSIONS: Exenatide once weekly holds promise as a convenient, efficacious, and well-tolerated antihyperglycemic agent for the treatment of type 2 diabetes. Studies evaluating outcomes such as cardiovascular events or all-cause mortality with exenatide once weekly are lacking. PMID- 22669805 TI - Computational and experimental analysis of the transmembrane domain 4/5 dimerization interface of the serotonin 5-HT(1A) receptor. AB - Experimental evidence suggests that most members of class A G-protein coupled receptors (GPCRs) can form homomers and heteromers in addition to functioning as single monomers. In particular, serotonin (5-HT) receptors were shown to homodimerize and heterodimerize with other GPCRs, although the details and the physiological role of the oligomerization has not yet been fully elucidated. Here we used computational modeling of the 5-HT(1A) receptor monomer and dimer to predict residues important for dimerization. Based on these results, we carried out rationally designed site-directed mutagenesis. The ability of the mutants to dimerize was evaluated using different FRET-based approaches. The reduced levels of acceptor photobleaching-Forster resonance energy transfer (FRET) and the lower number of monomers participating in oligomers, as assessed by lux-FRET, confirmed the decreased ability of the mutants to dimerize and the involvement of the predicted contacts (Trp175(4.64), Tyr198(5.41), Arg151(4.40), and Arg152(4.41)) at the interface. This information was reintroduced as constraints for computational protein-protein docking to obtain a high-quality dimer model. Analysis of the refined model as well as molecular dynamics simulations of wild type (WT) and mutant dimers revealed compensating interactions in dimers composed of WT and W175A mutant. This provides an explanation for the requirement of mutations of Trp175(4.64) in both homomers for disrupting dimerization. Our iterative computational-experimental study demonstrates that transmembrane domains TM4/TM5 can form an interaction interface in 5-HT(1A) receptor dimers and indicates that specific amino acid interactions maintain this interface. The mutants and the optimized model of the dimer structure may be used in functional studies of serotonin dimers. PMID- 22669806 TI - Maritime health: a review with suggestions for research. AB - International maritime health has largely developed within the sphere of occupational health services and international health problems. We reviewed publications in the journal International Maritime Health from 2000 to 2010 to establish the coverage of the journal and the scope of research in maritime health. We identified six thematic categories: healthcare access, delivery and integration; telehealth; non-communicable diseases and physical health problems; communicable diseases; psychological functioning and health; and safety-related issues. We describe the research within these themes and report on their publication prominence. We also analyse the research in terms of its geographical focus, the population groups addressed and the research methodologies used. We suggest a broadening of maritime research to include randomised controlled trials, longitudinal studies and more qualitative research; more research addressing the context for non-European seafarers; and research on seafarers spouses and family supports and obligations. We also recommend more research on psychosocial and cultural issues and on telehealth, as well as the development of a stronger systems perspective for promoting maritime health. PMID- 22669807 TI - Surveillance of maritime deaths on board Danish merchant ships, 1986-2009. AB - BACKGROUND: A previous study demonstrated a high death rate among seafarers signed on Danish ships during the years 1986-1993. This study aimed to examine and analyse the subsequent development until 2009. MATERIAL AND METHODS: A total of 356 fatalities were identified from data supplied from the Danish Maritime Authority, an insurance company, and other sources. Maritime deaths among seafarers signed on Danish ships comprise deaths from 1) accidents, suicides and homicides; and 2) disease on board. Deaths due to 2) occurring ashore within 30 days after signing off were included. The overall and mode-specific death rates were calculated for three eight-year observation periods. The rates for work related fatal accidents were compared with the rates for land-based trades. RESULTS: All categories of maritime deaths were significantly reduced from 1986 to 2009 - in particular during the last eight-year period (Accidents 1986-1993: 66.6 per 100,000 person years, 2002-2009: 27.0 per 100,000 person years, diseases 49.5-26.1, suicides 14.4-7.8). In spite of the remarkable improvement since 1986, seafarers remain in 2002-2009 more than six times more likely to die from occupational accidents (including shipwrecks) than do workers ashore. CONCLUSIONS: The favourable trend of maritime deaths in the Danish merchant fleet may be due to 1) preventive measures - e.g. interventions relating to vessel safety, work environment, and improved medical care on board - and to 2) technological and organizational changes - e.g. newer and larger vessels in the Danish merchant fleet, changed composition of the workforce, and reduced shore leaves. The persisting excess risk warrants further preventive actions. PMID- 22669808 TI - Infection control measures on ships and in ports during the early stage of pandemic influenza A (H1N1) 2009. AB - Shipping companies were surveyed to evaluate the effect of public health measures during the influenza A (H1N1) pandemic of 2009 on ship and port operations. Of 31 companies that operated 960 cruise, cargo, and other ships, 32% experienced health-screening measures by port health authorities. Approximately a quarter of ports (26%) performed screening at embarkation and 77% of shipping companies changed procedures during the early stage of the pandemic. Four companies reported outbreaks of pandemic influenza A (H1N1) 2009 on ships, which were ultimately stopped through infection control practices. Public health measures did not interfere substantially with port and ship operations with the exception of some port authorities that delayed embarking and disembarking procedures in a few ships. However, in the shipping companies' experience, measures were inconsistent between port health authorities. Access to antiviral drugs and pandemic vaccine was not provided in all ports. Current guidelines on medical care, hygiene, and emergency procedures on ships need to address pandemic influenza preparedness in future revisions. PMID- 22669809 TI - Awareness of health risks at the workplace and of risks of contracting communicable diseases including those related to food hygiene, among seafarers. AB - BACKGROUND: The awareness of health risks on board ships in terms of knowledge of dangers and discomfort at the workplace, and of risks of contracting communicable diseases including those related to food hygiene was assessed in a sample of workers of an Italian shipping company. Analysis was performed on crew members and on ashore personnel of the same firm to assess possible differences in risk perception. MATERIALS AND METHODS: The study was conducted by proposing an anonymous questionnaire to the crew members of 9 tankers and to the office staff of the shipping company Finaval S.p.A., which has its headquarters in Rome. RESULTS: People living ashore have a better knowledge of infectious risks than seafarers. Both ashore workers and seafarers have a reasonable awareness of blood borne and sexually-transmitted diseases. Seafarers are more concerned about the risks of psychological problems due to isolation than are office personnel. The risk of not being adequately cared for in case of disease or injury on board is also perceived as a major problem by seafarers. Ashore personnel, eating raw fish more than their mates on board, are at a greater risk of communicable gastrointestinal diseases. CONCLUSIONS: Seafarers should be the target of specific informative campaigns about health risks, possible consequences, and how to minimize exposure to them during travel/life at sea. PMID- 22669810 TI - Design for end-user acceptance: requirements for work clothing for fishermen in Mediterranean and northern fishing grounds. AB - Fishing is one of the most dangerous occupations, and as many as 24,000 fishermen around the world suffer fatal injuries or drowning at sea every year. Although fishermen in the European fishing fleet work in harsh and dangerous environments, many fishermen do not use personal protective clothing and buoyancy aids due to reduced work comfort and poor functionality. This emphasizes the importance of designing work clothing and personal protective equipment (PPE) with functionality that matches the fishermen's needs. The aim of this study was to identify the requirements for work clothing in terms of comfort, protection, and safety for fishermen operating in northern fishing grounds and in the Mediterranean. Furthermore, we investigated whether fishermen in the Mediterranean prioritize work-clothing requirements differently from fishermen in northern fishing grounds. Interviews and observations of fishermen provided us with the requirements for work clothing for fishermen. A questionnaire was then distributed to a selection of European fishermen. The study showed that fishermen operating in the Mediterranean prioritized their requirements differently from fishermen in northern fishing grounds. There was good agreement on requirements regarding work comfort. Safety requirements, such as integrated buoyancy, were ranked as less important by the Mediterranean fishermen compared to fishermen in northern fishing grounds. The results of this study provide a basis for the development of work clothing and PPE for fishermen. Work clothing and PPE that fulfil the requirements are likely to obtain end-user acceptance and thus improve safety for fishermen at sea. PMID- 22669811 TI - Occupational hazards for fishermen in the workplace in Polish coastal and beach fishing--a point of view. AB - The work of marine fishermen is considered one of the most dangerous and life threatening professions all over the world. There are some common features of the fishing occupation, such as: exposure to cold, wind, rough seas, substantial participation of physical effort, frequency of injuries during work, unpredictability and abruptness of threats, equipment failure, everyday psychological stress, and constant economic pressure. At the same time, the specificity and variety of hazards, depending significantly on geographical climate and cultural factors, makes the dissimilarity of problems and solutions substantial in different sectors of fishing. The present article is a review of the problems of Polish costal fishermen, referring to some local particularities within this extremely difficult profession requiring special predispositions. PMID- 22669812 TI - Extremely deep recreational dives: the risk for carbon dioxide (CO(2)) retention and high pressure neurological syndrome (HPNS). AB - Clear differences between professional and recreational deep diving are disappearing, at least when taking into account the types of breathing mixtures (oxygen, nitrox, heliox, and trimix) and range of dive parameters (depth and time). Training of recreational deep divers is conducted at depths of 120-150 metres and some divers dive to 180-200 metres using the same diving techniques. Extremely deep recreational divers go to depths of more than 200 metres, at which depths the physical and chemical properties of breathing gases create some physiological restrictions already known from professional deep diving. One risk is carbon dioxide retention due to limitation of lung ventilation caused by the high density of breathing gas mixture at great depths. This effect can be amplified by the introduction of the additional work of breathing if there is significant external resistance caused by a breathing device. The other risk for deep divers is High Pressure Neurological Syndrome (HPNS) caused by a direct compression effect, presumably on the lipid component of cell membranes of the central nervous system. In deep professional diving, divers use a mixture of helium and oxygen to decrease gas density, and nitrogen is used only in some cases for decreasing the signs and symptoms of HPNS. The same approach with decreasing the nitrogen content in the breathing mixture can also be observed nowadays in deep recreational diving. Moreover, in extremely deep professional diving, hydrogen has been used successfully both for decreasing the density of the breathing gas mixture and amelioration of HPNS signs and symptoms. It is fair to assume that the use of hydrogen will be soon "re-invented" by extremely deep recreational divers. So the scope of modern diving medicine for recreational divers should be expanded also to cover these problems, which previously were assigned exclusively to professional and military divers. PMID- 22669813 TI - Cardiomegaly in tropical Africa. AB - The term "cardiomegaly" is found in 5-7% of chest X-ray film evaluations in tropical Africa. However, "cardiomegaly" is a descriptive term, devoid of any aetiological meaning. Therefore, providing information about the aetiological factors leading to heart enlargement in a group of Africans (Nigerians) was the purpose of this study. In the years 2002-2011, 170 subjects (aged 17-80 years, mean age 42 years) in whom "cardiomegaly" was revealed by chest radiographs were studied at the Madonna University Teaching Hospital, Elele. The patients underwent echocardiography, electrocardiography, and several appropriate laboratory tests. Arterial hypertension was found to be most frequently associated with heart enlargement (39.4%), followed by dilated cardiomyopathy (21.76%), endomyocardial fibrosis (14.1%), valvular defects (9.4%), cardiac enlargement in the course of sickle-cell anaemia (6.47%), and schistosomal cor pulmonale (3.52%). This study is a contribution to a better aetiological elucidation of "cardiomegaly" in the tropics and emphasizes the importance of arterial hypertension as one of its causative factors. The dire need for effective treatment of hypertensive patients becomes evident. A high prevalence of elevated blood pressure seems to reflect an impact of civilization-related factors on the African communities. PMID- 22669814 TI - Outbreak of pulmonary histoplasmosis involving a group of four Polish travellers returning from Ecuador. AB - Exploring caves is, without doubt, a very exciting adventure; however, it carries some dangers. Three of four travellers were admitted to hospital with lung changes after returning from Ecuador, successively. Epidemiological studies revealed that the travellers visited caves infested by bats, and had contact with bats' guano. They gave a history of fever, fatigue, myalgia, dry cough, and chest pain during the stay or just after returning from Ecuador. In two patients, symptoms persisted in mild nature. Chest X-ray films showed diffuse nodules (coin-like lesions) in the lungs in each case. Histoplasmosis was taken into consideration. Differential diagnosis included paragonimiasis, pulmonary tuberculosis, and pulmonary infection of other causes. Direct examination of sputum was negative. Cultures were negative. Final diagnosis was made on epidemiological histories, as well as typical radiological changes, and was supported by positive tests for antibodies to Histoplasma capsulatum. Immunodiffusion test (ID), complement fixation test (CFTs), and Western blot test were positive. In two cases antifungal treatment was established. Ketoconazole followed by Itraconazole were used. Persons who are going to explore caves should be equipped with anti-dusk masks to prevent pulmonary histoplasmosis. The threat of Histoplasma capsulatum infection in bat-inhabited caves should be emphasized to travellers and also to physicians. PMID- 22669815 TI - Combined effects of work-related stress in Her Majesty's Coastguard (HMCG). AB - BACKGROUND: Having initially reported on the overall level of stress in Her Majesty's Coastguard (HMCG), in a second study we found that a combined (negative) effects approach to stress was better able to identify the associated psychosocial risk factors than by using the well-documented Effort-Reward Imbalance (ERI) or Job Demand-Control Support (JDCS) models alone. Using the same combined effects method, this study now examines the negative health and wellbeing outcomes associated with the level of high stress found in this occupational group. MATERIAL AND METHODS: Participants included 282 coastguards. A range of known stress outcomes were measured including: mental and physical health, accidents, risk taking, effects of memory, lifestyle, and job satisfaction. RESULTS: Significant associations were found with: anxiety, depression, number of sick days, perception that illness was caused or made worse by work, number of symptoms, medicines taken, insomnia, ability to maintain a desired body weight or take planned exercise and find time to relax and wind down, time spent on hobbies or interests, the impact of job on family life/family life on job, and job satisfaction. CONCLUSIONS: Sixteen negative outcomes were significantly associated with the combined effects approach, compared with 15 using ERI or 10 using JDCS alone. Results clearly demonstrated the harmful effects of stress in maritime related roles, other than those of seafarers and suggest that further research in this area would be useful. Further studies on the more flexible stress model, which allows for the examination of both established and new combinations of risk factors and associated outcomes, would also be beneficial. PMID- 22669816 TI - The effects of response cost and species-typical behaviors on a daily time-place learning task. AB - Two theories that have been hypothesized to mediate acquisition in daily time place learning (TPL) tasks were investigated in a free operant daily TPL task: the response cost hypothesis and the species-typical behavior hypothesis. One lever at the end of one of the choice arms of a T-maze provided food in the morning, and 6 h later, a lever in the other choice arm provided food. Four groups were used to assess the effect of two possible sources of response cost: physical effort of the task and costs associated with foraging ecology. One group was used to assess the effect of explicitly allowing for species-typical behaviors. If only first arm choice data were considered, there was little evidence of learning. However, both first press and percentage of presses on the correct lever prior to the first reinforcement revealed evidence of TPL in most rats tested. Unexpectedly, the high response cost groups for both of the proposed sources did not perform better than the low response cost groups. The groups that allowed animals to display species-typical behaviors performed the worst. Skip session probe trials confirmed that the majority of the rats that acquired the task were using a circadian timing strategy. The results from the present study suggest that learning in free operant daily TPL tasks might not be dependent on response cost. PMID- 22669817 TI - Access site-related complications after transradial catheterization can be reduced with smaller sheath size and statins. AB - The aim of this study was to investigate the risk factors for access site-related complications after transradial coronary angiography (CAG) or percutaneous coronary intervention (PCI). Transradial PCI has been shown to reduce access site related bleeding complications compared with procedures performed through a femoral approach. Although previous studies focused on risk factors for access site-related complications after a transfemoral approach or transfemoral and transradial approaches, it is uncertain which factors affect vascular complications after transradial catheterization. We enrolled 500 consecutive patients who underwent transradial CAG or PCI. We determined the incidence and risk factors for access site-related complications such as radial artery occlusion and bleeding complications. Age, sheath size, the dose of heparin and the frequency of PCI (vs. CAG) were significantly greater in patients with than without bleeding complications. However, body mass index (BMI) was significantly lower in patients with than without bleeding complications. Sheath size was significantly higher and the frequency of statin use was significantly lower in patients with than without radial artery occlusion. Multiple logistic analysis revealed that sheath size [odds ratio (OR) 5.5; P < 0.05] and BMI (OR 0.86; P < 0.01) were risk factors for bleeding complications; and sheath size (OR 5.2; P < 0.05) and the lack of statin pretreatment (OR 0.50; P < 0.05) were risk factors for occlusive complications. In conclusion, these findings indicate that down sizing of the devices used in transradial procedures might attenuate access site related complications after transradial CAG or PCI. Statin pretreatment might also be a strategy that could prevent radial artery occlusion after transradial procedures. PMID- 22669818 TI - Tudor domain proteins in development. AB - Tudor domain proteins function as molecular adaptors, binding methylated arginine or lysine residues on their substrates to promote physical interactions and the assembly of macromolecular complexes. Here, we discuss the emerging roles of Tudor domain proteins during development, most notably in the Piwi-interacting RNA pathway, but also in other aspects of RNA metabolism, the DNA damage response and chromatin modification. PMID- 22669819 TI - The Prdm family: expanding roles in stem cells and development. AB - Members of the Prdm family are characterized by an N-terminal PR domain that is related to the SET methyltransferase domain, and multiple zinc fingers that mediate sequence-specific DNA binding and protein-protein interactions. Prdm factors either act as direct histone methyltransferases or recruit a suite of histone-modifying enzymes to target promoters. In this way, they function in many developmental contexts to drive and maintain cell state transitions and to modify the activity of developmental signalling pathways. Here, we provide an overview of the structure and function of Prdm family members and discuss the roles played by these proteins in stem cells and throughout development. PMID- 22669820 TI - The developmental dismantling of pluripotency is reversed by ectopic Oct4 expression. AB - The transcription factors Nanog and Oct4 regulate pluripotency in the pre implantation epiblast and in derivative embryonic stem cells. During post implantation development, the precise timing and mechanism of the loss of pluripotency is unknown. Here, we show that in the mouse, pluripotency is extinguished at the onset of somitogenesis, coincident with reduced expression and chromatin accessibility of Oct4 and Nanog regulatory regions. Prior to somitogenesis expression of both Nanog and Oct4 is regionalized. We show that pluripotency tracks the in vivo level of Oct4 and not Nanog by assessing the ability to reactivate or maintain Nanog expression in cell culture. Enforced Oct4 expression in somitogenesis-stage tissue provokes rapid reopening of Oct4 and Nanog chromatin, Nanog re-expression and resuscitates moribund pluripotency. Our data suggest that decreasing Oct4 expression is converted to a sudden drop in competence to maintain pluripotency gene regulatory network activity that is subsequently stabilized by epigenetic locks. PMID- 22669822 TI - Regulation of neuronal differentiation at the neurogenic wavefront. AB - Signaling mediated by the Delta/Notch system controls the process of lateral inhibition, known to regulate neurogenesis in metazoans. Lateral inhibition takes place in equivalence groups formed by cells having equal capacity to differentiate, and it results in the singling out of precursors, which subsequently become neurons. During normal development, areas of active neurogenesis spread through non-neurogenic regions in response to specific morphogens, giving rise to neurogenic wavefronts. Close contact of these wavefronts with non-neurogenic cells is expected to affect lateral inhibition. Therefore, a mechanism should exist in these regions to prevent disturbances of the lateral inhibitory process. Focusing on the developing chick retina, we show that Dll1 is widely expressed by non-neurogenic precursors located at the periphery of this tissue, a region lacking Notch1, lFng, and differentiation related gene expression. We investigated the role of this Dll1 expression through mathematical modeling. Our analysis predicts that the absence of Dll1 ahead of the neurogenic wavefront results in reduced robustness of the lateral inhibition process, often linked to enhanced neurogenesis and the presence of morphological alterations of the wavefront itself. These predictions are consistent with previous observations in the retina of mice in which Dll1 is conditionally mutated. The predictive capacity of our mathematical model was confirmed further by mimicking published results on the perturbation of morphogenetic furrow progression in the eye imaginal disc of Drosophila. Altogether, we propose that Notch-independent Delta expression ahead of the neurogenic wavefront is required to avoid perturbations in lateral inhibition and wavefront progression, thus optimizing the neurogenic process. PMID- 22669821 TI - Neurogenin 2 regulates progenitor cell-cycle progression and Purkinje cell dendritogenesis in cerebellar development. AB - By serving as the sole output of the cerebellar cortex, integrating a myriad of afferent stimuli, Purkinje cells (PCs) constitute the principal neuron in cerebellar circuits. Several neurodegenerative cerebellar ataxias feature a selective cell-autonomous loss of PCs, warranting the development of regenerative strategies. To date, very little is known as to the regulatory cascades controlling PC development. During central nervous system development, the proneural gene neurogenin 2 (Neurog2) contributes to many distinct neuronal types by specifying their fate and/or dictating development of their morphological features. By analyzing a mouse knock-in line expressing Cre recombinase under the control of Neurog2 cis-acting sequences we show that, in the cerebellar primordium, Neurog2 is expressed by cycling progenitors cell-autonomously fated to become PCs, even when transplanted heterochronically. During cerebellar development, Neurog2 is expressed in G1 phase by progenitors poised to exit the cell cycle. We demonstrate that, in the absence of Neurog2, both cell-cycle progression and neuronal output are significantly affected, leading to an overall reduction of the mature cerebellar volume. Although PC fate identity is correctly specified, the maturation of their dendritic arbor is severely affected in the absence of Neurog2, as null PCs develop stunted and poorly branched dendrites, a defect evident from the early stages of dendritogenesis. Thus, Neurog2 represents a key regulator of PC development and maturation. PMID- 22669823 TI - COUP-TFII is essential for metanephric mesenchyme formation and kidney precursor cell survival. AB - Development of the metanephric kidney in mammals requires complex reciprocal tissue interactions between the ureteric epithelium and the mesenchyme. It is believed that Gdnf, produced in the metanephric mesenchyme, activates Ret signaling in the Wolffian duct to initiate the formation of the metanephros. However, the molecular mechanism for induction of Gdnf in the metanephric mesenchyme is not completely defined. Previous studies demonstrated that during the early stages of kidney development, loss of Osr1, Eya1, Pax2 or Wt1 gene function in the metanephric mesenchyme compromises the formation of the kidney. Moreover, it has been shown that the Hox11-Eya1-Pax2 complex activates the expression of Six2 and Gdnf in the metanephric mesenchyme to drive nephrogenesis. Here, we demonstrate that the orphan nuclear receptor chicken ovalbumin upstream promoter transcription factor II (COUP-TFII, also known as Nr2f2) is required for the specification of the metanephric mesenchyme. Deletion of COUP-TFII at E7.5 results in improper differentiation of the metanephric mesenchyme and absence of essential developmental regulators, such as Eya1, Six2, Pax2 and Gdnf. Importantly, we show that COUP-TFII directly regulates the expression of both Eya1 and Wt1 in the metanephric mesenchyme. Our findings reveal, for the first time, that COUP-TFII plays a central role in the specification of metanephric fate and in the maintenance of metanephric mesenchyme proliferation and survival by acting as a crucial regulator of Eya1 and Wt1 expression. PMID- 22669824 TI - A zebrafish Notum homolog specifically blocks the Wnt/beta-catenin signaling pathway. AB - Multiple developmental processes require tightly controlled Wnt signaling, and its misregulation leads to congenital abnormalities and diseases. Glypicans are extracellular proteins that modulate the Wnt pathway. In addition to interacting with Wnts, these glycosophosphotidylinositol (GPI)-anchored, heparan-sulfate proteoglycans bind ligands of several other signaling pathways in both vertebrates and invertebrates. In Drosophila, Notum, a secreted alpha/beta hydrolase, antagonizes the signaling of the prototypical Wnt Wingless (Wg), by releasing glypicans from the cell surface. Studies of mammalian Notum indicate promiscuous target specificity in cell culture, but the role of Notum in vertebrate development has not been studied. Our work shows that zebrafish Notum 1a, an ortholog of mammalian Notum, contributes to a self-regulatory loop that restricts Wnt/beta-catenin signaling. Notum 1a does not interact with Glypican 4, an essential component of the Wnt/planar cell polarity (PCP) pathway. Our results suggest a surprising specific role of Notum in the developing vertebrate embryo. PMID- 22669825 TI - Stable establishment of cotyledon identity during embryogenesis in Arabidopsis by ANGUSTIFOLIA3 and HANABA TARANU. AB - In seed plants, the shoot apical and root apical meristems form at the apical and basal poles of the embryonic axis, and leaves form at the flanks of the shoot apical meristem. ANGUSTIFOLIA3/GRF INTERACTING FACTOR1 (AN3/GIF1) encodes a putative transcriptional co-activator involved in various aspects of shoot development, including the maintenance of shoot apical meristems, cell proliferation and expansion in leaf primordia, and adaxial/abaxial patterning of leaves. Here, we report a novel function of AN3 involved in developmental fate establishment. We characterised an an3-like mutant that was found to be an allele of hanaba taranu (han), named han-30, and examined its genetic interactions with an3. an3 han double mutants exhibited severe defects in cotyledon development such that ectopic roots were formed at the apical region of the embryo, as confirmed by pWOX5::GFP expression. Additionally, gif2 enhanced the ectopic root phenotype of an3 han. Although the auxin accumulation pattern of the embryo was correct in an3 han-30, based on DR5rev::GFP expression at the globular stage, expression of the PLETHORA1 (PLT1), a master regulator of root development, expanded from the basal embryonic region to the apical region during the same developmental stage. Furthermore, the plt1 mutation suppressed ectopic root formation in an3 han. These data suggest that establishing cotyledon identity requires both AN3 and HAN to repress ectopic root formation by repressing PLT1 expression. PMID- 22669826 TI - Specific dermatoses of pregnancy: a review. AB - BACKGROUND: Some dermatoses worsen during pregnancy, some improve, yet others have unpredictable course. OBJECTIVE: To conduct evidence-based search, and review of current management of specific dermatoses of pregnancy. METHODS: Comprehensive literature search was conducted, with Medline and Cochrane Database regarding skin diseases in pregnancy from 1990- 2005. International pharmaceutical abstracts science search (1997- 2003) was used for search references found in the articles. All articles selected for inclusion in this review were evaluated critically with regards to their impact factor, source, and evidence based contribution on this topic as measured by their citation index and the journals they were published in. This review was limited to specific dermatoses of pregnancy generally and some of the skin disorders modified by pregnancy. RESULTS: Intrahepatic cholestasis of pregnancy should be managed as high risk pregnancies as several investigations have shown foetal complications. Recent randomised trials have demonstrated beneficial effects of ursodeoxycholic acid (UDCA) in intrahepatic cholestasis of pregnancy (ICP). Pruritice ruption of pregnancy is associated with multiple pregnancies. It has variable clinical features and has to be differentiated from pemphigoid gestationis, which is associated with an increased incidence of both prematurity and small for date's babies. Prurigo of pregnancy is extremely itchy with papules appearing on the extensor surfaces of the limbs and trunk. It has no maternal risk. The eruptions in pruritic folliculitis of pregnancy clear spontaneously in the postpartum period, with no associated morbidity either in the mother or baby. CONCLUSION: Some skin diseases like obstetric cholestasis may have adverse foetal outcome, while other disorders like pruritic folliculitis of pregnancy have no significant effect on either the mother or baby. PMID- 22669827 TI - Unsafe abortion and its ethical, sexual and reproductive rights implications. AB - BACKGROUND: Unsafe abortion is an important cause of maternal mortality and morbidity, particularly marked in developing countries with restrictive abortion laws. It has both bioethical and human rights implications, violating their key principles and components. OBJECTIVE: To highlight the magnitude of complications of unsafe abortion and examine the legal,bioethical, sexual and reproductive right implications of unsafe abortion as well as to review post abortion care (PAC) in Nigeria. DATA SOURCE: Information derived from online web-search, literature review of articles from learned journals, serials and monographs from local and supra-national agencies working on abortion, and reproductive health. RESULTS: About 20 million unsafe abortions are performed annually globally resulting in about 80, 000 maternal deaths. Asia and Africa have the highest number of maternal deaths. In Nigeria, 760, 000 abortions are performed annually. Abortion law in Nigeria is restrictive. Unsafe abortion violates three key bioethical principles at micro and mega-ethical levels. It also violates eleven of the twelve components of sexual and reproductive rights. PAC is approved as an effective approach to reducing abortion morbidity and mortality and promoting women's reproductive rights. CONCLUSION: Stakeholders can promote the ethical, sexual and reproductive rights of women through the following interventions: advocacy, liberalization of restrictive abortion law, training of health workers on PAC services, inter-organisational collaboration, development of right based code of ethics and inclusion into medical training curriculum. Socio-economic empowerment of women, provision of PAC services equipments in health facilities, and improvement of access to quality family planning services will also help promote the rights of women. PMID- 22669828 TI - Epidemiological characteristics and trends of caesarean delivery in a University Hospital in Northern Greece. AB - BACKGROUND: Current obstetric practice is characterised by a continuous increase in caesarean section (CS) delivery rates. OBJECTIVE: Main purpose of our study was to estimate the overall and annual rates of CS in a University Hospital in Greece. METHODS: This was a retrospective chart review of all singleton pregnancies delivered by CS between 2004 and 2008 at a gestational age > 24 weeks. The overall and annual CS rates were calculated. The rate of elective (Group 1) and emergency CS (Group 2) , as well as the specific indications in the two groups of the study were also analyzed. RESULTS: Overall 5362 singleton pregnancies were delivered in the period of the study. The overall CS rate was 29.2% (n = 1564). The mean +/-SD maternal age in years of the women delivered by CS was 29.65 +/- 6.72 years, while it was 27.10 +/-5.63 years for those who delivered vaginally (P<0.0001). The overall rates of elective and emergency CS were 18.2% and 11.0% respectively in the 5-year period of the study. The most common indication for an elective CS was a previous CS (63.1%), which remained almost stable during the period of the study. The main indication for emergency CS was foetal distress in the first three years of the study, while labour progress failure was the leading indication in the last two years. CONCLUSION: In this series, the overall CS rate was high. A previous caesarean delivery accounts for about one third of all cases and constitutes the leading indication for elective CS while foetal distress is the most common indication for an emergency caesarean section. PMID- 22669829 TI - Clinicopathological characteristics of odontogenic myxoma in Nigerians. AB - BACKGROUND: Odontogenic myxoma (OM) is a locally aggressive neoplasm whose clinicopathological characteristics have not been extensively reported in Nigerians. OBJECTIVE: To describe the clinicopathological characteristics of cases of OM seen at the Lagos University Teaching Hospital in Nigeria. METHODS: A review of both clinical and histopathological records of sixty-three cases of OM diagnosed over a period of thirty-seven years was undertaken. The cases were analyzed for age, sex, site, size, duration and histological contents of collagenization, odontogenic epithelium and calcification. RESULTS: Odontogenic myxoma represented 63(11.2%) cases of odontogenic tumours, was commonest in the second to forth decades and rare below age 10 and above 70 years. It was more common in females. Maxillary lesions were more common with respect to both central and peripheral histologic types, but occurred in equal frequencies in mandible and maxilla with respect to the central histologic type. Forty-seven (74.6%) cases were fibromyxoma and sixteen (25.4%) myxoma. Odontogenic epithelium was rare and observed in 5 (9.5%) cases while calcific material was present in sixteen (25.4%) cases. Late presentation was a common feature and surgical excision was the treatment of choice. CONCLUSION: Odontogenic myxoma is un-common among Nigerians when compared with ameloblastoma. Clinicopathological characteristics in this series are similar to information in the scientific literature. PMID- 22669830 TI - Nutritional status of children with sickle cell disease at Korle Bu Teaching Hospital, Accra, Ghana. AB - BACKGROUND: Sickle cell disease (SCD) with its attendant increased energy requirements has an adverse effect on growth. Good nutrition is essential for normal childhood growth and development. Differences in growth between children living within the same SEC's are likely to be due to the effects of the sickle cell disease. OBJECTIVE: To determine the relationship between SCD and nutritional status in children. METHODS: This cross-sectional study, conducted at the Paediatric Sickle Cell Clinic of the Korle Bu Teaching Hospital, recruited 427 children aged 1-12 years: 357 SCD patients (cases) and 70 of their siblings with Hb AA (controls), over a four-month period. Their socio-demographic data, weight and height/length were documented, and the weight-for-age (WAZ) and height/length-for-age (HAZ), weight-for-height/length (WHZ) scores calculated as indices of nutritional status. RESULTS: The mean (SD) age of SCD participants was 7.18 (3.15) years and of controls was 5.13 (3.28) years, (p=0.8). The prevalence of malnutrition was 61.3% among SCD subjects and 28.6% among controls, (p<0.001). The WAZ (underweight) and HAZ (stunting) scores were significantly more common among SCD children than controls, but the difference in the rates of wasting (WHZ) was not significant (p=0.3). CONCLUSION: Ghanaian SCD children are more underweight and stunted than their Hb AA counterparts living under similar socio economic conditions. Better education of families about the nutritional needs of SCD children in our community is needed. PMID- 22669831 TI - Urinary tract infection in febrile children with sickle cell anaemia. AB - BACKGROUND: Sickle cell anaemia (SCA) is very common in Maiduguri, North-Eastern Nigeria. Children with this disease have increased tendency to develop frequent and severe infections especially of the urinary tract, bones and lungs. The prevalence of urinary tract infection (UTI) has however not been reported in this part of the Nigeria. OBJECTIVE: To determine the prevalence of bacteriuria and bacterial isolates in the urine of febrile children with sickle cell anaemia. METHODS: This was a prospective study carried out on 250 children with SCA and 250 controls with HbAA aged 6 months to 15 years. Following clinical assessment, midstream urine or urine obtained by suprapubic bladder aspiration was collected and subjected to microscopy and culture. RESULTS: Bacteriuria was found in 65 (26%) of children with SCA and controls 514 (20.4%) of controls, p>0.05. Escherichia coli [16 (27.7%)] and Klebsiella species [16(24.6%)] were the predominant isolates in SCA group, while Escherichia coli [13(37.3%)] and Coliforms (25.4%) were predominant in the control group. Significant bacteruria occurred in patients with other clinical conditions such as pneumonia and septicaemia. CONCLUSION: Urinary tract infection is common in children with SCA. Routine screening is therefore recommended during febrile illnesses. PMID- 22669832 TI - An audit of laparoscopic surgeries in Ile-Ife, Nigeria. AB - BACKGROUND: After several years of lagging behind due to several constraints, many general surgeons across Nigeria are now performing laparoscopic surgery. An audit of the procedure in our setting is required. OBJECTIVE: To describe the outcome of consecutive laparoscopic general surgical procedures performed at the Obafemi Awolowo University Teaching Hospital, South-western Nigeria. METHODS: All patients with general surgical conditions who had laparoscopic surgery from January 2009 through May 2010 in our hospital were prospectively studied and type of pre, intra and postoperative data including sex, age, indication for surgery, and outcome of the procedure were obtained and analysed. RESULTS: Sixty-two patients (ages 18 to 72 years) had laparoscopic surgeries within the study period. Eighteen (29%) patients had laparoscopic cholecystectomy, 13 (21%) had laparoscopic appendicectomy, 10 (16.1%) had laparoscopic adhesiolysis, 7 (11.3%) laparoscopic biopsies of intraabdominal masses while 14(22.6%) others had diagnostic laparoscopies for a range of suspected abdominal conditions. All diagnostic procedures were performed as day cases while the duration of hospital stay was one to two days for the therapeutic procedures. Two(3%) procedures, including a biopsy of hepatic mass and a cholecystectomy were converted to open surgery due to significant haemorrhage. A minor bile duct injury was recorded in one patient who had cholecystectomy and superficial port site wound infections were noticed in two patients who had appendectomy. No mortality was recorded. CONCLUSION: Our results show the feasibility of laparoscopic surgery in Nigeria. We advocate local adaptation and improvisations to increase the use of laparoscopic surgery in Nigerian hospitals. PMID- 22669833 TI - Relationship between serum testosterone levels and features of the metabolic syndrome defining criteria in patients with type 2 diabetes mellitus. AB - BACKGROUND: There are increasing reports on the association between the testosterone deficiency syndrome (TDS) and increased risk of development of the metabolic syndrome - a well recognized cardiovascular risk factor in men with diabetes mellitus. OBJECTIVE: To determine the relationship between serum testosterone levels and components of the metabolic syndrome in Type 2 diabetes mellitus in Nigerian men. METHODS: A total of 203 men with type 2 DM aged 30-86 years were evaluated for the testosterone deficiency syndrome (TDS). The diagnosis of the TDS or hypogonadism was made using a combination of clinical features of hypogonadism and subnormal levels of total testosterone. The presence of the metabolic syndrome was sought for in those with and without the TDS. The metabolic syndrome was diagnosed using the new criteria by the International Diabetes Federation and related bodies. RESULTS: The overall prevalence rates of the TDS and the metabolic syndrome in the study subjects were 36% and 44% respectively. The proportion of the subjects with the Metabolic Syndrome (METS) was comparable in subjects with and without the TDS. (47% vs 43%, p = 0.6). Using the Mann Whitney U test, the mean rank of the testosterone level in the subjects with the METS was lower than that of those without the METS but this difference was not statistically significant (67.2 vs 66, p =0.9). CONCLUSION: The frequency of occurrence of the metabolic syndrome in men with type 2DM is comparable in those with hypogonadism and those without hypogonadism. There is no correlation between serum testosterone levels and the metabolic syndrome defining parameters. PMID- 22669834 TI - Methicillin resistant Staphylococcus aureus: awareness, knowledge and disposition to screening among healthcare workers in critical care units of a Nigerian hospital. AB - BACKGROUND: Awareness level about methicillin resistant Staphylococcus aureus (MRSA) is high in the western world but the status in developing countries is not well defined. OBJECTIVE: To assess MRSA awareness level, knowledge and disposition to screening among critical healthcare givers (HCGs) in Nigeria. METHODS: A self-administered questionnaire was used to assess the level of awareness and knowledge of HCGs in critical care units of the University of Ilorin Teaching Hospital, Ilorin, Nigeria on MRSA and their willingness to submit to screening. RESULTS: Only 103 (52.0%) of the 198 participants were aware of MRSA but all were favourably disposed to screening for the organism. Awareness was through hospital rounds 65(63.1%) and journals/ textbooks 35(34.0%), and Many, 120 (60.6%) considered MRSA as a threat in the hospital, while only 27 (13.6%) thought otherwise and 51(25.8%) were indifferent. Most HCGs, 124 (87.9%) reported that there were no MRSA control measures in their respective duty post. The age, cadre of work, and number of years in the hospital's critical care units correlated positively with awareness level. CONCLUSION: Methicillin resistant Staphylococcus aureus awareness level among the HCGs in our hospital is just a little above 50.0% with substantial proportion of them not realizing the medical implication of the organism. However, majority are well disposed to MRSA screening. Inadequate publicity is a major contributor to poor knowledge and awareness. There is need for educational intervention and sensitization programs on MRSA and other infection control techniques for HCGs in developing nations especially Nigeria. PMID- 22669835 TI - The electrical axis of the heart in nigerian patients with chronic obstructive lung disease in Benin City. AB - BACKGROUND: Of the electrocardiographic changes in chronic obstructive lung disease (COLD) patients, a shift of the P wave axis greater than 900 which is highly characteristic, is said to be due to hyperinflation and does not occur in interstitial lung disease. OBJECTIVE: To describe the electrocardiographic changes in chronic obstructive lung disease patients. METHODS: The electrical axis of the various waves of the ECG using the hexiaxial reference system in 92 Nigerian patients with COLD were examined, 39 of whom had associated cor pulmonale. P wave axis greater than 900 was present in 2(19.1%) of 17 patients with COLD alone and 15(41.7%) out of 36 with development of corpulmonale (p<0.001). The mean P wave axis was 64.7 +/- 10.6 0 in those without cor pulmonale while it was significantly shifted to the right (83.90) in those with cor pulmonale. The mean QRS axis was 53.50 +/- 21.20 and 89.0 +/-12.40 in those without and with cor pulmonale respectively (p=0.7716). The QRS axis was normal in all but one of those without cor pulmonale while there was a right axis deviation in 51.7% of those with it. ST and T wave changes were mainly present in those with associated cor pulmonale. CONCLUSION: The study shows that a shift of the electrical axis of the heart occurs in COLD patients mainly with the development of right ventricular hypertrophy (cor pulmonale), rather than the hyperinflation. PMID- 22669836 TI - Hepatitis B viral markers in surface antigen negative blood donors: the need to look beyond antibody negativity. AB - BACKGROUND: The presence of Hepatitis B Virus (HBV) in blood that is Hepatitis B Surface Antigen (HBsAg) negative is considered a potential risk for transmission of hepatitis B virus infection. OBJECTIVE: To determine prevalence of antibodies to markers of hepatitis B virus infection in HBsAg negative prospective blood donors. METHODS: A structured questionnaire to assess prospective donor's demographic data and past medical history was administered to 457 consenting HBsAg negative subjects. All the subjects were also negative for antibodies to hepatitis C virus (HCV), human immunodeficiency virus (HIV) and syphilis. Their serum samples were tested for the presence of anti-HBc, anti-HBe, anti-HBs and HBeAg. RESULTS: Of the 457 samples tested, 20 (4.37%), 58 (12.69%), 1 (0.22%), and 1 (0.22%) were positive to anti-HBc, anti-HBs, anti-HBe, and HBeAg antibodies, respectively. Ten (50%) of those who were positive for HBc antibody were also positive to anti-HBe and anti-HBs. Similarly, two (3.4%) donors who were positive for anti-HBs were also positive for HBeAg and anti-HBe. Of the 20 who were anti-HBc positive, seven had tattoo/traditional marks on their body and one had previous history of blood transfusion. CONCLUSION: This study has shown that some potential blood units containing HBV are being transfused to patients unknowingly by screening for HBsAg only. Screening for other markers of hepatitis B virus may increase the rejection rate, but will reduce HBV transmission. PMID- 22669837 TI - Knowledge and practice of breast cancer screening among female nurses and lay women in Osogbo, Nigeria. AB - BACKGROUND: Breast cancer is the most common cancer among African women. Most researchers have attributed the late presentation to poor knowledge of breast cancer symptoms. OBJECTIVE: This study was designed to evaluate the relationship between knowledge and practice of breast cancer screening in two groups of women with different levels of knowledge of breast carcinoma. METHODS: A cross sectional study was conducted using self administered questionnaire to assess the knowledge, attitudes and practice of breast cancer and screening programmes among nurses in a university teaching hospital, and women in non health professionals in south-western Nigeria. RESULTS: The mean knowledge score for the nurses was 10.9%+/-3.6 whereas the mean score for non-health professionals was 3.5%+/-4.1 (p value < 0.001). In those above the age of 40 years, comprising 141 subjects, 35 nurses and 106 women in non-health professionals, 22.9% and 15% respectively had had a mammogram (p=0.289,1.123). CONCLUSION: Good knowledge does not imply better screening rates in south-western Nigeria. PMID- 22669838 TI - Complications and causes of death in spinal cord injury patients in Nigeria. AB - BACKGROUND: There have been many reports on the problems of spinal cord injury (SCI) in Nigeria but few have reported on the complications and causes of death in spinal cord injured patients. OBJECTIVE: The objective of this study was to determine the complications, causes of death and associated risk factors in patients with SCI within six months post injury. METHODS: Patients were retrospectively identified from the hospital trauma database from January 1997 to December 2007. Complications and cause of death within the first six months of SCI were determined along with associated risk factors. RESULTS: Five hundred and eighty-two patients were eligible for analyses and data were obtained for 422 (72.5%) patients with a mean age of 37.2 (+/-14.2) years at six months follow-up. Muscle spasms 417 (98.8%) and neurogenic pain 382 (94.5%) were the main complications noted. The mortality during the review period was 144 (34.1%). Respiratory failure (44.4%) was the commonest cause of death. The independent predictors of mortality were mainly age, GCS<9, Frankel Type A at presentation and cervical spine injury (CSI) and while CSI and Frankel Type A injury were the main predictors of complications. CONCLUSION: Most common complication and cause of death following SCI are muscle spasm and respiratory failure respectively. The risk factors associated with mortality are age, GCS<9, cervical spinal injury, and complete neurologic injury and those for complications were cervical spinal injury and Frankel Type A injury. PMID- 22669839 TI - Orbital metastasis of hepatocellular carcinoma: a case report. AB - BACKGROUND: Hepatocellular carcinoma is one of the commonest malignancies in Nigeria, however metastasis to the orbit is a rare presentation. OBJECTIVE: To present a rare case of orbital metastasis of hepatocellular carcinoma. CASE REPORT: A 25-year-old man presented with a 3-month history of pain, progressive swelling and burred vision of the right eye. Examination revealed marked proptosis of the right eye with reduced visual acuity and conjunctival chemosis. The liver was enlarged, hard and nodular. Hepatocellular carcinoma and orbital metastasis were histologically confirmed. CONCLUSION: Metastatic hepatocellular carcinoma should be considered in the differential diagnosis of patients presenting with orbital tumours. PMID- 22669840 TI - Are all Semitic languages immune to letter transpositions? The case of Maltese. AB - Recent research using the rapid serial visual presentation (RSVP) paradigm with English sentences that included words with letter transpositions (e.g., jugde) has shown that participants can readily reproduce the correctly spelled sentences with little cost; in contrast, there is a dramatic reading cost with root-derived Hebrew words (Velan & Frost, Psychonomic Bulletin & Review 14:913-918, 2007, Cognition 118:141-156, 2011). This divergence could be due to (1) the processing of root-derived words in Semitic languages or (2) the peculiarities of the transitional probabilities in root-derived Hebrew words. Unlike Hebrew, Maltese is a Semitic language that does not omit vowel information in print and whose morphology also has a significant non-Semitic (mostly Romance) morphology. Here, we employed the same RSVP technique used by Velan and Frost (Psychonomic Bulletin & Review 14:913-918, 2007, Cognition 118:141-156, 2011), this time with Maltese (and English) sentences. The results showed that Maltese-English bilinguals were able to reproduce the Maltese words-regardless of whether they were misspelled (involving the transposition of two letters from the consonantal root) or not, with no reading cost-just as in English. The apparent divergences between the RSVP data with Hebrew versus Maltese sentences are likely due to the combination of the characteristics of the Hebrew orthographic system with the Semitic morphology. PMID- 22669841 TI - Tissue-specific mRNA expression patterns reveal a coordinated metabolic response associated with genetic selection for milk production in cows. AB - The molecular mechanisms regulating the physiological adaptation of tissues important for nutrient partitioning and metabolism in lactating cows are still not completely understood. The aim of our study was to identify tissue-specific regulatory mechanisms necessary to accommodate metabolic changes associated with different genetic potential for milk performance. For this purpose, we analyzed mRNA expression of genes involved in energy metabolism of segregating F(2) beef type cows with a combined genetic dairy and beef background (Charolais * German Holstein cross, CH*GH) in contrast to purebred German Holstein (GH) dairy cows. Three groups of cows differing in milk performance were examined using quantitative real-time PCR in liver, mammary gland, and skeletal muscle. Our results describe substantial tissue-specific differences in mRNA transcription profiles between cow groups in relation to their genetic potential for milk performance and highlight genes exhibiting specific, partially yet-unknown functions in dairy and beef type cows, e.g., upregulation of PCK2 transcripts in the mammary gland and FBP2 transcripts in skeletal muscle of dairy cows. Noticeably, PCCA and PPARGC1A mRNA abundance varied significantly across experimental groups in all three tissues, pointing to potential key gene functions in the metabolic adaptation relative to divergent milk production performance. Correlations of mRNA expression levels to milk performance traits indicate that gene transcriptional processes may play a regulatory role in liver, mammary gland, and skeletal muscle to enable cows with different genetic potential for milk performance to cope with metabolic lactation-associated challenges. PMID- 22669843 TI - F-box proteins elongate translation during stress recovery. AB - Protein synthesis is energetically costly and is tightly regulated by evolutionarily conserved mechanisms. Under restrictive growth conditions and in response to various stresses, such as DNA damage, cells inhibit protein synthesis to redirect available adenosine triphosphate to more essential processes. Conversely, proliferating cells, such as cancer cells, increase protein synthetic rates to support growth-related anabolic processes. mRNA translation occurs in three separate phases, consisting of initiation, elongation, and termination. Although all three phases are highly regulated, most of the translational control occurs at the rate-limiting initiation step. New evidence has described a molecular mechanism involved in the regulation of translation elongation. DNA damage initially slowed down elongation rates by activating the eukaryotic elongation factor 2 kinase (eEF2K) through an adenosine monophosphate (AMP) activated protein kinase (AMPK)-dependent mechanism. However, during checkpoint recovery, the SCF (Skp, Cullin, F-box-containing) betaTrCP (beta-transducin repeat-containing protein) E3 ubiquitin ligase promoted degradation of eEF2K, thereby allowing the restoration of peptide chain elongation. These findings establish an important link between DNA damage signaling and the regulation of translation elongation. PMID- 22669842 TI - Role of genetic modifiers in an orthologous rat model of ARPKD. AB - Human data and animal models of autosomal recessive polycystic kidney disease (ARPKD) suggest that genetic factors modulate the onset and severity of the disease. We report here for the first time that ARPKD susceptibility is attenuated by introgressing the mutated Pkhd1 disease allele from the polycystic kidney (PCK) rat onto the FHH (Fawn-Hooded Hypertensive) genetic background. Compared with PCK, the FHH.Pkhd1 strain had significantly decreased renal cyst formation that coincided with a threefold reduction in mean kidney weights. Further analysis revealed that the FHH. Pkhd1 is protected from increased blood pressure as well as elevated plasma creatinine and blood urea nitrogen levels. On the other hand, liver weight and biliary cystogenesis revealed no differences between PCK and FHH.Pkdh1, indicating that genes within the FHH genetic background prevent the development of renal, but not hepatic, manifestations of ARPKD. Microarray expression analysis of kidneys from 30-day-old PCK rats revealed increased expression of genes previously identified in PKD renal expression profiles, such as inflammatory response, extracellular matrix synthesis, and cell proliferation genes among others, whereas the FHH.Pkhd1 did not show activation of these common markers of disease. This newly developed strain can serve as a tool to map modifier genes for renal disease in ARPKD and provides further insight into disease variability and pathophysiology. PMID- 22669844 TI - Labeling and identification of direct kinase substrates. AB - Identifying kinase substrates is an important step in mapping signal transduction pathways, but it remains a difficult and time-consuming process. Analog-sensitive (AS) kinases have been used to selectively tag and identify direct kinase substrates in lysates from whole cells. In this approach, a gamma-thiol adenosine triphosphate analog and an AS kinase are used to selectively thiophosphorylate target proteins. Thiophosphate is used as a chemical handle to purify peptides from a tryptic digest, and target proteins are identified by liquid chromatography and tandem mass spectrometry (LC-MS/MS). Here, we describe an updated strategy for labeling AS kinase substrates, solid-phase capture of thiophosphorylated peptides, incorporation of stable isotope labeling in cell culture for filtering nonspecific background peptides, enrichment of phosphorylated target peptides to identify low-abundance targets, and analysis by LC-MS/MS. PMID- 22669846 TI - Matrix rigidity controls endothelial differentiation and morphogenesis of cardiac precursors. AB - Tissue development and regeneration involve tightly coordinated and integrated processes: selective proliferation of resident stem and precursor cells, differentiation into target somatic cell type, and spatial morphological organization. The role of the mechanical environment in the coordination of these processes is poorly understood. We show that multipotent cells derived from native cardiac tissue continually monitored cell substratum rigidity and showed enhanced proliferation, endothelial differentiation, and morphogenesis when the cell substratum rigidity closely matched that of myocardium. Mechanoregulation of these diverse processes required p190RhoGAP, a guanosine triphosphatase activating protein for RhoA, acting through RhoA-dependent and -independent mechanisms. Natural or induced decreases in the abundance of p190RhoGAP triggered a series of developmental events by coupling cell-cell and cell-substratum interactions to genetic circuits controlling differentiation. PMID- 22669845 TI - Coupled activation and degradation of eEF2K regulates protein synthesis in response to genotoxic stress. AB - The kinase eEF2K [eukaryotic elongation factor 2 (eEF2) kinase] controls the rate of peptide chain elongation by phosphorylating eEF2, the protein that mediates the movement of the ribosome along the mRNA by promoting translocation of the transfer RNA from the A to the P site in the ribosome. eEF2K-mediated phosphorylation of eEF2 on threonine 56 (Thr56) decreases its affinity for the ribosome, thereby inhibiting elongation. Here, we show that in response to genotoxic stress, eEF2K was activated by AMPK (adenosine monophosphate-activated protein kinase)-mediated phosphorylation on serine 398. Activated eEF2K phosphorylated eEF2 and induced a temporary ribosomal slowdown at the stage of elongation. Subsequently, during DNA damage checkpoint silencing, a process required to allow cell cycle reentry, eEF2K was degraded by the ubiquitin proteasome system through the ubiquitin ligase SCF(betaTrCP) (Skp1-Cul1-F-box protein, beta-transducin repeat-containing protein) to enable rapid resumption of translation elongation. This event required autophosphorylation of eEF2K on a canonical betaTrCP-binding domain. The inability to degrade eEF2K during checkpoint silencing caused sustained phosphorylation of eEF2 on Thr56 and delayed the resumption of translation elongation. Our study therefore establishes a link between DNA damage signaling and translation elongation. PMID- 22669847 TI - Intravitreal pegaptanib as adjunctive treatment for stage 3+ ROP shown to be effective in a prospective, randomized, controlled multicenter clinical trial. AB - PURPOSE: Both intravitreal pegaptanib with laser therapy and intravitreal bevacizumab monotherapy have been found to be more efficacious than laser therapy alone in prospective, randomized, controlled clinical trials. RESULTS: The use of pegaptanib with laser therapy was efficacious in 91.2% compared with 69.0% in controls. The use of bevacizumab monotherapy was efficacious in 95.7% compared with 78.1% in controls. CONCLUSIONS: The use of anti-vascular endothelial growth factor therapy for retinopathy of prematurity has been shown to be efficacious, without toxicity reported to date; however, the best drug and dose which allows greatest efficacy with fewest recurrences and without toxicity must be determined. PMID- 22669848 TI - Intravitreal pegaptanib combined with diode laser therapy for stage 3+ retinopathy of prematurity in zone I and posterior zone II. AB - PURPOSE: To investigate efficacy of intravitreal injection of pegaptanib and laser photocoagulation for treatment of stage 3+ retinopathy of prematurity (ROP) affecting zone I and posterior zone II, and to compare the results in terms of regression, development of peripheral retinal vessels, and final structural outcome with conventional laser photocoagulation or combined with cryotherapy. METHODS: In a prospective comparative study, 152 eyes with zone I, II posterior ROP 3+ (76 premature rabies), from 2009 to 2011, were included. Patients were randomly assigned to receive intravitreal pegaptanib (Macugen(r) 0.3 mg = 0.02 mL, Pfizer) with conventional diode laser photocoagulation in group 1 (68 eyes of 34 infants) or only laser therapy combined with cryotherapy in group 2 (84 eyes of 42 infants), bilaterally. The primary outcome of treatment success was defined as absence of recurrence of stage 3+ ROP. The mean follow-up after treatment was 19.3 months in group 1 and 21.5 months in group 2. RESULTS: Final favorable anatomic outcome and stable regression of ROP at last control examination was noted in 89.7% of eyes in group 1 and 60.8 % of eyes in group 2. Regression of plus disease and peripheral retinal vessels development appeared significantly more rapidly in group 1. No recurrence of neovascularization (stage 3+ ROP) was identified in 85.4% of patients in group 1 and 50% of patients in group 2. CONCLUSIONS: Results of this study support the administration of intravitreal pegaptanib as useful therapy in the management of stage 3+ ROP. PMID- 22669849 TI - Through the looking glass: evaluating the dissemination of research in cardiology. PMID- 22669850 TI - From abstract to impact in cardiovascular research: factors predicting publication and citation. AB - AIMS: Through a 4-year follow-up of the abstracts submitted to the European Society of Cardiology Congress in 2006, we aimed at identifying factors predicting high-quality research, appraising the quality of the peer review and editorial processes, and thereby revealing potential ways to improve future research, peer review, and editorial work. METHODS AND RESULTS All abstracts submitted in 2006 were assessed for acceptance, presentation format, and average reviewer rating. Accepted and rejected studies were followed for 4 years. Multivariate regression analyses of a representative selection of 10% of all abstracts (n= 1002) were performed to identify factors predicting acceptance, subsequent publication, and citation. A total of 10 020 abstracts were submitted, 3104 (31%) were accepted for poster, and 701 (7%) for oral presentation. At Congress level, basic research, a patient number >= 100, and prospective study design were identified as independent predictors of acceptance. These factors differed from those predicting full-text publication, which included academic affiliation. The single parameter predicting frequent citation was study design with randomized controlled trials reaching the highest citation rates. The publication rate of accepted studies was 38%, whereas only 24% of rejected studies were published. Among published studies, those accepted at the Congress received higher citation rates than rejected ones. CONCLUSIONS: Research of high quality was determined by study design and largely identified at Congress level through blinded peer review. The scientometric follow-up revealed a marked disparity between predictors of full-text publication and those predicting citation or acceptance at the Congress. PMID- 22669851 TI - Bilateral distal tibial stress fractures in a military recruit. AB - Stress fractures are common injuries in athletes and military recruits. They result from repetitive microtrauma, which over time exceeds the bone's intrinsic ability to repair itself. The site of occurrence is most commonly the weight bearing lower limb. Such injuries are easily missed as the history and clinical signs are often not consistent with an acute injury and therefore may not warrant an x-ray on first presentation to the emergency department or primary care. Even when plain radiographs are taken, the fractures may not be initially evident and in the presence of a high index of clinical suspicion, further investigations may be necessary. We present the case of a military recruit who developed bilateral distal tibial stress fractures early on in his training. PMID- 22669852 TI - A rare case of portal vein gas: accidental hydrogen peroxide ingestion. AB - Hydrogen peroxide (H(2)O(2)) is a colourless and odourless liquid with oxidant characteristics used for various purposes. Whereas in lower concentrations (3%), H(2)O(2) is used as a disinfectant in home cleaning products and wound care, in higher concentrations (35%) it is used in textile and paper industry as a bleaching agent and is diluted for use in lightening hair dyes. Like other caustic substances, direct injuries may develop if H(2)O(2) is swallowed and systemic air embolisms may occur due to the resultant gaseous oxygen. This study discusses a patient who was detected with the presence of gas in the portal venous system due to H(2)O(2) intoxication and was treated conservatively. PMID- 22669853 TI - Intraperitoneal urinary bladder fistula caused by a Foley catheter: a successfully conservative management. PMID- 22669855 TI - Enterocolitis with multiple ulcers of ileum and right colon in a patient with leukaemia attributed to cytomegalovirus. PMID- 22669854 TI - Life-threatening calcium channel blocker overdose and its management. AB - A young woman presented to the emergency department with complaints of nausea, vomiting, pain in the abdomen and difficulty in breathing after ingestion of 56 tablets of amlodipine 5 mg each (total 280 mg of amlodipine). She was managed using hyperinsulinaemia/euglycaemia therapy and other measures like calcium gluconate, glucagon and vasopressors. She was discharged from hospital in a stable condition after 5 days. PMID- 22669856 TI - Exercise-induced anaphylaxis. AB - A 23-year-old man presented with acute flushing, pruritus and warmth followed by collapse after vigorous exercise in a gymnasium. After resting for 30 min and receiving a rapid infusion of 0.9% sodium chloride, he was finally stable. He admitted that he had a similar experience 5 years earlier during exercise. Based on the patient's history, his symptoms were attributed to exercise-induced anaphylaxis. None of his episodes was associated with any suspicious co-triggers of anaphylaxis. He was successfully discharged from hospital without any complications after receiving guidance on how to prevent this condition. PMID- 22669857 TI - Unilateral isolated extraocular muscle lymphoma. AB - The authors would like to present an unusual case of ocular adnexal, mucosa associated lymphoid tissue lymphoma, isolated to a single extraocular muscle. A 59-year-old woman presented with a 3-month history of slowly progressive double vision, worse on elevation, for which her optometrist had given her prisms. A swollen left upper eyelid was present for 10 days. CT scan of the brain and orbits revealed a 3 cm * 1.5 cm mass arising from the region of the left superior rectus with no signs of bone erosion. Histology showed infiltration by small lymphoid cells. Stage 1AE low-grade marginal zone B cell lymphoma was diagnosed. Possible aetiologies included Chlamydia psittaci infection and the recently recognised IgG4-related sclerosing disease. After oral doxycycline 200 mg once a day failed to show improvement, localised radiotherapy 30 Gy resulted in excellent clinical and radiological resolution of this isolated lymphoma. PMID- 22669858 TI - Superior subluxation of an anterior end of the first rib in a trauma patient. AB - We present a case of a young man with a superior subluxation of an anterior end of the first rib following a road traffic accident. To the best of our knowledge, no similar case has so far been described in the literature. The patient presented with headache, backache and pain in the right anterior chest wall. After initial assessment, a chest radiograph was performed and it showed no abnormalities. A CT of the chest revealed an isolated hypermobile first rib at the anterior end owing to superior subluxation. The patient was treated conservatively. PMID- 22669859 TI - Primary disseminated extrahepatic abdominal hydatid cyst: a rare disease. AB - Hydatid disease (HD) is a parasitic disease, most frequently caused by Echinococcus granulosus or Echinococcus multilocularis and rarely by Echinococcus vogeli or Echinococcus oligarthus. Mostly, hydatid cyst is primarily in liver (75%) and lung (15%). Peritoneal HD (13%) is usually secondary. Dissemination of HD may occur following rupture of the hydatid cyst into the peritoneal cavity. Primary peritoneal hydatid cyst disease is a rare phenomenon. We present a case of primary disseminated abdominal HD presenting with the complaint of a pain in the epigastric region along with intermittent fever. Radiological evaluation and serological examination confirmed it as primary disseminated HD involving pancreas, a cyst anterior to the left lobe of the liver just below the peritoneum and the left kidney. PMID- 22669860 TI - Typhlitis: a neutropenic complication. PMID- 22669861 TI - Breast necrotising fasciitis managed by partial mastectomy. AB - We present the case of a 75-year-old woman who presented with extensive breast cellulitis, which was thought to be secondary to a deep breast abscess. On admission the patient underwent debridement of the breast and broad-spectrum intravenous antibiotics were administered. However, during hospitalisation she developed sepsis, acute renal failure and required further debridements for the rapidly spreading necrotising fasciitis. Subsequently, a partial mastectomy was performed and the patient made an overall good postoperative recovery. PMID- 22669862 TI - Ruptured renal calyx mimicking leaking abdominal aortic aneurysm. AB - The case of an 81-year-old man with a known 5.2 cm abdominal aortic aneurysm (AAA) and transitional cell carcinoma of the bladder who presented to the emergency department in painful clot retention is described. Approximately 5 h after starting bladder irrigation he developed a sudden onset of severe abdominal pain radiating to his back. Urgent CT scan (AAA protocol) revealed a rupture of the lower pole calyx of his right kidney and a stable aneurysm. Bladder irrigation was stopped and the patient settled with a catheter and simple analgesia. Given his significant co-morbidities, it was felt that surgical intervention for the underlying malignancy was inappropriate and the patient was discharged home. At last outpatient review, his renal function was at its baseline and he was suffering no ill-effects from the ruptured kidney. PMID- 22669863 TI - Totally laparoscopic resection of a rare duodenal tumour. AB - A 39-year-old woman presented to the gastroenterology clinic with recurrent right upper-quadrant pain and elevated liver enzymes. Endoscopy revealed a small submucosal mass at the edge of the major duodenal papilla, which was not amenable to endoscopic resection. The mass was successfully resected by laparoscopy. The papilla was subsequently reconstructed and a cannula inserted in the common bile duct. The postoperative period was uneventful and the patient was discharged on the third postoperative day. Subsequent pathological examination of the excised mass revealed a gangliocytic paraganglioma. Six weeks later, the patient was free of symptoms and the cannula was removed by duodenoscopy. PMID- 22669864 TI - Malignant peripheral nerve sheet tumour of cervix. AB - Sarcomas account for less than 1% of malignancies of the uterine cervix. Among them, rhabdomyosarcomas are the ones most frequently reported. Malignant peripheral nerve sheet tumour (MPNST) is very rare. In this paper we present a 53 year-old woman with MPNST of the uterine cervix. PMID- 22669865 TI - Rupture of an inferior epigastric artery pseudo-aneurysm following laparoscopic port insertion. AB - Laparoscopic port insertion is a potential cause of trauma to the inferior epigastric artery, resulting in pseudo-aneurysm formation. Treatment of pseudo aneurysms includes thrombin injection, coil embolisation, embolisation with N butyl cyanoacrylate, compression therapy or surgical excision and ligation. The authors present a case of pseudo-aneurysm caused by port insertion during laparoscopic sigmoid colectomy. The pseudo-aneurysm was identified using CT and Doppler ultrasound scans, but underwent spontaneous resolution with cessation of flow prior to intervention. The patient was therefore discharged, but he presented again as an emergency with rupture of a clinically infected pseudo aneurysm and needed emergency surgical intervention. PMID- 22669866 TI - Non-Hodgkin's lymphoma presenting as a mediastinal mass in a 38-year-old patient with superior vena cava syndrome and extreme fatigue owing to left atrium and right ventricle outflow tract compression: the applicability of strain imaging. PMID- 22669868 TI - Breathlessness and new de-saturation in a patient with congenital heart disease: a time to thrombolyse or to seek specialist help? AB - A patient with known repaired complex congenital heart disease was referred as an emergency with increasing breathlessness on exertion. He was not short of breath at rest and had a saturation of 85% in air. A CT pulmonary angiography demonstrated decreased flow from his right ventricle to pulmonary artery, which was thought to be due to pulmonary embolism. We reviewed the CT with a knowledge and understanding of his anatomy and found that he had developed a false aneurysm of his right ventricular outflow tract, which required surgical treatment. PMID- 22669867 TI - Spontaneous rupture of utero-ovarian vessels in pregnancy. AB - Spontaneous rupture of utero-ovarian vessels in pregnancy is rare and usually involves utero-ovarian veins. Presenting symptoms include acute-onset abdominal pain and maternal hypovolemic shock secondary to haemoperitoneum. Although this condition had been documented over a century ago, an accurate diagnosis is rarely reached prior to laparotomy due to a multitude of other surgical and obstetrical presentations that may pose a similar clinical picture. In such an event an emergency exploratory laparotomy followed by caesarean section with ligation of the uterine vessels can help in preventing a maternal mortality. PMID- 22669869 TI - Neonatal thyrotoxicosis presenting as persistent pulmonary hypertension. AB - Neonatal hyperthyroidism is a rare condition caused either by transplacental passage of thyroid-stimulating immunoglobulins from a mother with Graves' disease or by activating mutations of the thyrotropin receptors and alpha-subunit of G protein. The clinical features may vary. We report a case of neonatal thyrotoxicosis in an infant born to a mother with Graves' disease, who presented with cardiorespiratory failure and persistent pulmonary hypertension (PPHN). PPHN resolved with specific antithyroid treatment and extracorporeal membrane oxygenation was not required. PMID- 22669870 TI - Life-threatening ANCA-positive vasculitis associated with rickettsial infection. AB - We present a 47-year-old Caucasian fire fighter who developed multisystem organ failure in the setting of a positive antineutrophil cytoplasmic autoantibody (myeloperoxidase) as well as confirmed Rocky Mountain spotted fever by skin biopsy PCR. This case provided a diagnostic challenge, a rare association of a Rickettsia infection and autoimmune vasculitis as well as a unique management approach. PMID- 22669871 TI - Abscess or tumour? Lumbar spinal abscess mimicking a filum terminale tumour. AB - A 62-year-old woman presented with a 4-month history of central lower backache and a 2-week history of progressive bilateral leg weakness. She also complained of numbness on her left thigh and gluteal region, associated with urinary hesitancy and constipation. On examination, she had bilateral partial foot drop, absent knee and ankle reflexes and a negative Babinski's reflex and associated hyperaesthesia in L3 distribution bilaterally with decreased anal tone. Laboratory results revealed normal inflammatory markers. MRI scan demonstrated a large uniformly enhancing lesion in the filum terminale suggestive of a lumbar spinal tumour. An emergency spinal laminectomy from L3 to S2 was performed. Per operatively, the duramater was thickened and hyperaemic. The histopathology report suggested inflammation with no evidence of malignancy. Tissue specimen of cultured Staphylococcus aureus was sensitive to flucloxacillin. A final diagnosis of lumbar spinal abscess was made and subsequent antibiotic treatment led to good clinical recovery. PMID- 22669872 TI - Large-vessel GCA or a late presentation of Takayasu's arteritis? AB - Giant cell arteritis (GCA) is a vasculitis that involves medium- and large-sized vessels. Typically presenting with localised headache, temporal artery tenderness, jaw claudication and ophthalmological complications, it can also affect large vessels, leading to limb claudication. We describe a patient presenting with acute coronary syndrome but who was also noted to have absent upper limb pulses, leading to a speculative diagnosis of GCA. According to the American College of Rheumatology, the patient met the criteria for both giant cell arteritis and Takayasu's arteritis. The gold standard investigation for diagnosing GCA is the temporal artery biopsy. Although contemplated, it was argued by the reviewing rheumatologist that this would not alter her management. She was thus commenced on prednisolone 60 mg daily, which led within 2 days to a rapid fall in erythrocyte sedimentation rate to 66 mm/h, and by day 11 this had dropped further to 4 mm/h. PMID- 22669873 TI - Shingles with secondary asymptomatic CNS involvement! AB - A 32-year-old married Asian woman, previously fit and well, presented with a 3 day history of interscapular back pain followed by a 1-day history of frontal headache and a few episodes of vomiting. She did not have photophobia or neck stiffness. On examination, there was evidence of herpes zoster infection involving the right T3 dermatome. There were no signs of meningeal irritation, cognitive impairment or any neurological deficit. As it is uncommon to have reactivation of herpes zoster infection at a young age, HIV serology was requested to exclude immunodeficiency state. While awaiting serology, a lumbar puncture was performed to exclude opportunistic infections of the central nervous system as she had transient headache and vomiting at the onset. The cerebrospinal fluid showed an elevated level of protein, an increase in lymphocytes and a strongly positive PCR for varicella zoster. The HIV test was negative. Oral acyclovir was changed to intravenous therapy and, a week later, she was discharged with uneventful recovery. PMID- 22669874 TI - Multiple large infected scrotal sebaceous cysts masking Fournier's gangrene in a 32-year-old man. AB - Extensive large sebaceous cysts on the scotum are rare and present a problem only when infected or when cosmesis is deemed unacceptable by the patient. Fournier's gangrene is an infective condition with a high death rate. We describe a case of Fournier's gangrene in a patient masked by multiple large infected scrotal sebaceous cysts. A 32-year-old man with a history of alcohol dependency, cirrhosis and multiple scrotal sebaceous cysts presented with acute scrotal pain and erythema. Necrosis of the area became evident within 12 h of his admission and an emergency surgical debridement was performed. The wound was left open to heal via secondary intention over 4 weeks without complication. Fournier's gangrene is a rapidly progressive condition and early surgical debridement is crucial to achieve satisfactory outcomes. In this case, prompt intervention allowed a large scrotal defect to heal without the need for skin grafting. PMID- 22669875 TI - Nasal chondromesenchymal hamartoma with no nasal symptoms. AB - The authors present a case of nasal chondromesenchymal hamartoma (NCMH) in an 8 year-old boy with a 4-month history of frontal headache and no symptoms of nasal obstruction, rhinorrhoea or postnasal drip. An ENT examination as well as ophthalmology assessment presented normal results. CT scan showed a lesion involving the sphenoid and ethmoid sinuses. The patient had an endoscopic resection of the lesion that was confirmed histologically to be a NCMH. Though NCMH is known to present usually in infants with obstructing nasal mass, an unusual presentation of a patient with throbbing headache without any nasal symptoms is reported here. PMID- 22669876 TI - Artefacts in the amplitude-integrated EEG background pattern of a full-term asphyxiated neonate caused by diaphragm spasms. AB - The amplitude-integrated EEG (aEEG) is used to detect neonatal seizures in neonates with asphyxia, and despite limited data-information compared with standard EEG, aEEG is increasingly used as routine monitoring in neonatal intensive care units due to the logistic advantages. In addition, the aEEG background is of prognostic value in these infants. However, aEEG artefacts can lead to an erroneous interpretation of the background pattern. We report a full term infant with severe perinatal asphyxia with diaphragm spasms that caused a significant alteration in aEEG background pattern. After administration of a neuromuscular blocker, the aEEG background transformed from discontinuous low voltage pattern to a flat trace. The aEEG background pattern can be misinterpreted by electrical activity of non-cerebral origin. Administration of neuromuscular blockers is a rapid method to differentiate between cerebral and muscular activity on the aEEG when EEG is not (yet) available. PMID- 22669877 TI - Spontaneous sublingual haematoma: a rare entity. AB - Sublingual haematoma, also known as pseudo-Ludwig phenomenon, is an entity commonly described in patients on anticoagulation therapy. Spontaneous sublingual haematoma is a rare subtype. It is thought to be due to aneurismal changes in the facial or lingual arteries, occurring mostly in the elderly hypertensive population. Two case reports of spontaneous sublingual haematomas have been reported so far in the literature. Both cases were elderly patients and presented with a sublingual mass and elevation of the floor of the mouth. One patient was intubated whereas the other underwent an emergency tracheotomy. The authors present the third case of spontaneous sublingual haematoma that was afebrile and had a sudden onset of sore throat that progressed to dyspnoea and required a life saving tracheotomy. The patient recovered quickly postoperatively and could be discharged home in a couple of days and was decannulated in 1 week. No recurrence of the haematoma was noticed on follow-up after 1 year. PMID- 22669878 TI - Atypical toxoplasmic retinochoroiditis. AB - We report a case of re-activation of Toxoplasma gondii as a cause of atypical retinal necrosis in an immunocompetent individual. The rapid development of necrotising confluent retinochoroiditis and vitreous inflammation necessitated urgent aqueous humor PCR analysis, which was positive for T gondii. The patient was treated with two intravitreal injections of clindamycin, along with oral sulphadiazine, pyrimethamine, folinic acid and prednisolone. He developed central retinal arterial occlusion, as a complication of toxoplasmic retinochoroiditis, and immediate anterior chamber paracentesis was performed with visual recovery. The injection of intravitreal clindamycin with concomitant oral therapy was associated with control of toxoplasmic retinochoroiditis and resolution of vitreous inflammation. PMID- 22669879 TI - Extensive thrombophlebitis with gas associated with continuous infusion of vancomycin through a central venous catheter. PMID- 22669880 TI - A rare and unusual case of urethral bleeding. AB - A 46-year-old man presented with urethral trauma following the unusual sexual practice of urethral sounding. He was able to urinate freely and was treated conservatively. He did not require any follow-up. Urethral sounding is uncommon sexual practice, where commonly a metal object is inserted per urethra for gratification. This practice is actively discouraged because of the long-term risks from urethral trauma. PMID- 22669881 TI - Arabidopsis MYC2 interacts with DELLA proteins in regulating sesquiterpene synthase gene expression. AB - Arabidopsis thaliana flowers emit volatile terpenes, which may function in plant insect interactions. Here, we report that Arabidopsis MYC2, a basic helix-loop helix transcription factor, directly binds to promoters of the sesquiterpene synthase genes TPS21 and TPS11 and activates their expression. Expression of TPS21 and TPS11 can be induced by the phytohormones gibberellin (GA) and jasmonate (JA), and both inductions require MYC2. The induction of TPS21 and TPS11 results in increased emission of sesquiterpene, especially (E)-beta caryophyllene. DELLAs, the GA signaling repressors, negatively affect sesquiterpene biosynthesis, as the sesquiterpene synthase genes were repressed in plants overaccumulating REPRESSOR OF GA1-3 (RGA), one of the Arabidopsis DELLAs, and upregulated in a penta DELLA-deficient mutant. Yeast two-hybrid and coimmunoprecipitation assays demonstrated that DELLAs, represented by RGA, directly interact with MYC2. In yeast cells, the N terminus of MYC2 was responsible for binding to RGA. MYC2 has been proposed as a major mediator of JA signaling and crosstalk with abscisic acid, ethylene, and light signaling pathways. Our results demonstrate that MYC2 is also connected to GA signaling in regulating a subset of genes. In Arabidopsis inflorescences, it integrates both GA and JA signals into transcriptional regulation of sesquiterpene synthase genes and promotes sesquiterpene production. PMID- 22669883 TI - Diffuse primary large B cell lymphoma of leg type presenting on the breast: a rare case of surgical excision. AB - Primary breast lymphoma is a rare subtype of breast malignancy whose diagnosis relies on histopathological characteristics and a high index of suspicion in clinically unusual presentations of breast pathology. The authors report a rare case of diffuse primary large B cell lymphoma of leg type presenting as a single lesion confined to the breast. Unusually for this subtype of lymphoma, the lesion was surgically excised and the patient, to date, has made an uneventful recovery. PMID- 22669884 TI - Acute ischaemic ventricular inferoseptal defect in a pyretic patient: a diagnostic challenge. AB - A 78-year-old Caucasian male presented with a 5-day progressive history of fever, vomiting and dyspnoea. Initial clinical examination revealed fever, sinus tachycardia, hypotension, peripheral cyanosis and a systolic murmur. Investigations revealed a multiple organ dysfunction syndrome. A repeat trans thoracic echocardiogram showed a basal inferoseptum aneurysm associated with an acquired ventricular septal defect not demonstrated on initial scan. An intra aortic balloon pump was urgently inserted and he underwent surgical repair of the defect, 7 days after his initial presentation. He unfortunately died from postoperative complications. PMID- 22669885 TI - Brown tumour of the jaw. AB - Brown tumours are classic bony lesions that arise as a result of the effect of parathyroid hormone on bone tissue in some patients with hyperparathyroidism. They are erosive bony lesions caused by rapid osteolysis and peritrabecular fibrosis, resulting in a local destructive phenomenon. Facial skeleton is involved in about 2% of all cases of which the mandible is frequently affected. A 35-year-old female who was diagnosed with osteomalacia and brown tumour in posterior mandible as the sign of secondary hyperparathyroidism secondary to vitamin D deficiency is presented. PMID- 22669886 TI - Intraductal tubulopapillary neoplasm of the pancreas as a radiation induced malignancy. AB - Pancreatic malignancies account for 3% of all cancer diagnoses in the UK and prognosis is poor with overall 1-year survival rates at 20% and 5-year survival rates at 5%. The majority of these cancers (75%-95%) arise from the exocrine part of the gland and are almost all invasive ductal adenocarcinomas. One per cent of all pancreatic tumours are endocrine tumours. There is limited data regarding the management of such rare neoplasms of the pancreas and some evidence suggests that prognoses and risk factors may be different. Therefore, it is important to report experience of this type of malignancy in order to build a knowledge base to guide the practice of future clinicians. The authors report a case of an intraductal tubulopapillary neoplasm of the pancreas. This is very unusual form of intraductal pancreatic tumour, which is now thought to occupy a distinct histological subcategory and has arisen within a previously irradiated field. PMID- 22669887 TI - Purine nucleoside phosphorylase deficiency with a novel PNP gene mutation: a first case report from India. AB - The authors report a case of purine nucleoside phosphorylase (PNP) deficiency for the first time from India. The case presented with recurrent severe infections, developmental delays, seizures and progressive neurological deterioration. The diagnosis of primary immunodeficiency disorder was delayed in spite of recurrent infection due to predominant neurological symptoms. Sequencing of the PNP gene revealed a novel mutation resulting in a premature stop codon. PMID- 22669882 TI - Plant peroxisomes: biogenesis and function. AB - Peroxisomes are eukaryotic organelles that are highly dynamic both in morphology and metabolism. Plant peroxisomes are involved in numerous processes, including primary and secondary metabolism, development, and responses to abiotic and biotic stresses. Considerable progress has been made in the identification of factors involved in peroxisomal biogenesis, revealing mechanisms that are both shared with and diverged from non-plant systems. Furthermore, recent advances have begun to reveal an unexpectedly large plant peroxisomal proteome and have increased our understanding of metabolic pathways in peroxisomes. Coordination of the biosynthesis, import, biochemical activity, and degradation of peroxisomal proteins allows for highly dynamic responses of peroxisomal metabolism to meet the needs of a plant. Knowledge gained from plant peroxisomal research will be instrumental to fully understanding the organelle's dynamic behavior and defining peroxisomal metabolic networks, thus allowing the development of molecular strategies for rational engineering of plant metabolism, biomass production, stress tolerance, and pathogen defense. PMID- 22669888 TI - Oesophageal tuberculosis. AB - The case discussed is that of a previously healthy 48-year-old female who presented with a week long history of epigastric pain and continuing weight loss. A series of investigations and supporting literature alluded to a diagnosis of oesophageal tuberculosis (TB), and antituberculous medication was commenced accordingly. An accompanying discussion considers the incidence, differential diagnoses, pathogenesis, clinical features, investigations and aspects of management of oesophageal TB. PMID- 22669889 TI - Isolated posterior cruciate ligament calcification. AB - The authors present a case of calcified posterior cruciate ligament (PCL). A 61 year-old female presented in our department reporting 12 months history of knee pain that was getting worse during the night. The patient was under medication for epileptic seizure, osteoporosis and hyperthyroidism. X-rays demonstrated calcification of the PCL. CT and MRI excluded any other intra-articular and extra articular pathology. Arthroscopic debridement of the calcium deposits was performed and the symptoms resolved immediately, while the postoperative x-rays were normal. Histological examination confirmed the calcium nature of the lesion. Two years postoperatively the patient remains asymptomatic. PMID- 22669890 TI - Thirteen square centimetre mass causing syncope in a patient with device related infective endocarditis. AB - A 68-year-old man presented with anorexia, weight loss and severe asthenia starting 2 months before and fever lasting over 2 weeks. Analytical study revealed increased C reactive protein and sedimentation velocity. While thoracic x-ray and urinalysis were unremarkable, blood cultures were consistently positive for Enterococcus faecalis. A thoracic echocardiogram revealed a very large vegetation adherent to the ventricular electrocatheter of the patient's pacemaker, so parenteral antibiotics were started. During his stay at the internal medicine ward, patient suffered three syncopal episodes and maintained intermittent fever. A transesophageal ECG performed at a tertiary centre on the 14th day unmasked a 9-12 cm(2) organised mass, ovoid and with regular borders, adherent to the ventricular electrocatheter at right atrium level and protruding to the ventricle at systole. Patient was referred for cardiothoracic surgery and a 13 cm(2) mass was removed alongside the ventricular electrocatheter. Two weeks following surgery, patient remains stable and asymptomatic. PMID- 22669891 TI - Punctate vascular expression1 is a novel maize gene required for leaf pattern formation that functions downstream of the trans-acting small interfering RNA pathway. AB - The maize (Zea mays) gene RAGGED SEEDLING2-R (RGD2-R) encodes an ARGONAUTE7-like protein required for the biogenesis of trans-acting small interfering RNA, which regulates the accumulation of AUXIN RESPONSE FACTOR3A transcripts in shoots. Although dorsiventral polarity is established in the narrow and cylindrical leaves of rgd2-R mutant plants, swapping of adaxial/abaxial epidermal identity occurs and suggests a model wherein RGD2 is required to coordinate dorsiventral and mediolateral patterning in maize leaves. Laser microdissection-microarray analyses of the rgd2-R mutant shoot apical meristem identified a novel gene, PUNCTATE VASCULAR EXPRESSION1 (PVE1), that is down-regulated in rgd2-R mutant apices. Transcripts of PVE1 provide an early molecular marker for vascular morphogenesis. Reverse genetic analyses suggest that PVE1 functions during vascular development and in mediolateral and dorsiventral patterning of maize leaves. Molecular genetic analyses of PVE1 and of rgd2-R;pve1-M2 double mutants suggest a model wherein PVE1 functions downstream of RGD2 in a pathway that intersects and interacts with the trans-acting small interfering RNA pathway. PMID- 22669893 TI - CAV1 siRNA reduces membrane estrogen receptor-alpha levels and attenuates sexual receptivity. AB - Although classic estrogen receptors (ER) have been proposed to mediate estradiol signaling, it has been relatively recently that mechanisms of trafficking these receptors have been elucidated. ERalpha is palmitoylated and associates with caveolin proteins to be targeted to the cell membrane. Caveolins are scaffold proteins that not only traffic ERalpha to the membrane but also are involved in establishing metabotropic glutamate receptor interactions that are necessary for activating G protein signaling. To demonstrate the role of caveolin proteins in regulating an estradiol-dependent behavior, sexual receptivity, we used small interfering RNA to knock down caveolin-1 (CAV1) expression in the arcuate nucleus of the hypothalamus. In CAV1 knockdown rats, membrane, but not intracellular levels of ERalpha, were significantly reduced. As expected, estrogenic stimulation of the arcuate nucleus of the hypothalamus to medial preoptic nucleus projection was abrogated in CAV1 knockdown rats, indicating that the membrane initiated activation of this circuit was compromised. Moreover, estradiol-induced lordosis behavior that is dependent on activation of MU-opioid receptors in the medial preoptic nucleus was also significantly reduced. Thus, CAV1-mediated ERalpha trafficking to the cell membrane is required for estradiol activation of circuits underlying female sexual receptivity. PMID- 22669892 TI - Differential expression of the Chlamydomonas [FeFe]-hydrogenase-encoding HYDA1 gene is regulated by the copper response regulator1. AB - The unicellular green alga Chlamydomonas reinhardtii adapts to anaerobic or hypoxic conditions by developing a complex fermentative metabolism including the production of molecular hydrogen by [FeFe]-hydrogenase isoform1 (HYDA1). HYDA1 transcript and hydrogenase protein accumulate in the absence of oxygen or copper (Cu). Factors regulating this differential gene expression have been unknown so far. In this study, we report on the isolation of a Chlamydomonas mutant strain impaired in HYDA1 gene expression by screening an insertional mutagenesis library for HYDA1 promoter activity using the arylsulfatase-encoding ARYLSULFATASE2 gene as a selection marker. The mutant strain has a deletion of the COPPER RESPONSE REGULATOR1 (CRR1) gene encoding for CRR1, indicating that this SQUAMOSA-PROMOTER BINDING PROTEIN (SBP) domain transcription factor is involved in the regulation of HYDA1 transcription. Treating the C. reinhardtii wild type with mercuric ions, which were shown to inhibit the binding of the SBP domain to DNA, prevented or deactivated HYDA1 gene expression. Reporter gene analyses of the HYDA1 promoter revealed that two GTAC motifs, which are known to be the cores of CRR1 binding sites, are necessary for full promoter activity in hypoxic conditions or upon Cu starvation. However, mutations of the GTAC sites had a much stronger impact on reporter gene expression in Cu-deficient cells. Electrophoretic mobility shift assays showed that the CRR1 SBP domain binds to one of the GTAC cores in vitro. These combined results prove that CRR1 is involved in HYDA1 promoter activation. PMID- 22669894 TI - Insulin deficiency alters the metabolic and endocrine responses to undernutrition in fetal sheep near term. AB - Insulin deficiency affects the adult metabolic response to undernutrition, but its effects on the fetal response to maternal undernutrition remain unknown. This study examined the effects of maternal fasting for 48 h in late gestation on the metabolism of fetal sheep made insulin deficient by pancreatectomy (PX). The endocrine and metabolic responses to maternal fasting differed between intact, sham-operated and PX fetuses, despite a similar degree of hypoglycemia. Compared with intact fetuses, there was no increase in the plasma concentrations of cortisol or norepinephrine in PX fetuses during maternal fasting. In contrast, there was a significant fasting-induced rise in plasma epinephrine concentrations in PX but not intact fetuses. Umbilical glucose uptake decreased to a similar extent in both groups of fasted animals but was associated with a significant fall in glucose carbon oxidation only in intact fetuses. Pancreatectomized but not intact fetuses lowered their oxygen consumption rate by 15-20% during maternal fasting in association with increased uteroplacental oxygen consumption. Distribution of uterine oxygen uptake between the uteroplacental and fetal tissues therefore differed with fasting only in PX fetuses. Both groups of fetuses produced glucose endogenously after maternal fasting for 48 h, which prevented any significant fall in the rate of fetal glucose utilization. In intact but not PX fetuses, fasting-induced glucogenesis was accompanied by a lower hepatic glycogen content. Chronic insulin deficiency in fetal sheep therefore leads to changes in the counterregulatory endocrine response to hypoglycemia and an altered metabolic strategy in dealing with nutrient restriction in utero. PMID- 22669895 TI - A Fall in plasma free fatty acid (FFA) level activates the hypothalamic-pituitary adrenal axis independent of plasma glucose: evidence for brain sensing of circulating FFA. AB - The brain responds to a fall in blood glucose by activating neuroendocrine mechanisms for its restoration. It is unclear whether the brain also responds to a fall in plasma free fatty acids (FFA) to activate mechanisms for its restoration. We examined whether lowering plasma FFA increases plasma corticosterone or catecholamine levels and, if so, whether the brain is involved in these responses. Plasma FFA levels were lowered in rats with three independent antilipolytic agents: nicotinic acid (NA), insulin, and the A1 adenosine receptor agonist SDZ WAG 994 with plasma glucose clamped at basal levels. Lowering plasma FFA with these agents all increased plasma corticosterone, but not catecholamine, within 1 h, accompanied by increases in plasma ACTH. These increases in ACTH or corticosterone were abolished when falls in plasma FFA were prevented by Intralipid during NA or insulin infusion. In addition, the NA-induced increases in plasma ACTH were completely prevented by administration of SSR149415, an arginine vasopressin receptor antagonist, demonstrating that the hypothalamus is involved in these responses. Taken together, the present data suggest that the brain may sense a fall in plasma FFA levels and activate the hypothalamic pituitary-adrenal axis to increase plasma ACTH and corticosterone, which would help restore FFA levels. Thus, the brain may be involved in the sensing and control of circulating FFA levels. PMID- 22669896 TI - Phytoestrogen genistein up-regulates endothelial nitric oxide synthase expression via activation of cAMP response element-binding protein in human aortic endothelial cells. AB - We previously reported that genistein, a phytoestrogen, up-regulates endothelial nitric oxide synthase (eNOS) and prevents hypertension in rats that are independent of estrogen signaling machinery. However, how genistein regulates eNOS expression is unknown. In the present study, we show that genistein enhanced eNOS expression and NO synthesis in primary human aortic endothelial cells. Inhibition of extracellular signal regulated kinase, phosphoinositol-3 kinase, or protein kinase C did not affect genistein-enhanced eNOS expression and NO synthesis. However, chemical inhibition of protein kinase A (PKA) or adenoviral transfer of the specific endogenous PKA inhibitor gene completely abolished PKA activity and genistein-stimulated eNOS expression and NO production. Accordingly, genistein induced PKA activity and subsequent phosphorylation of cAMP response element (CRE)-binding protein (CREB) at Ser133. Suppression of CREB by small interfering RNA transfection abolished genistein-enhanced eNOS expression and NO production. Consistently, deletion of the CRE site within human eNOS promoter eliminated genistein-stimulated eNOS promoter activity. These findings provide the first evidence to our knowledge that genistein may play a beneficial role in vascular function through targeting the PKA/CREB/eNOS/NO signaling pathway. PMID- 22669897 TI - Antihypertensive role of tissue kallikrein in hyperaldosteronism in the mouse. AB - Tissue kallikrein (TK) is synthesized in arteries and distal renal tubule, the main target of aldosterone. Urinary kallikrein excretion increases in hyperaldosteronism. We tested the hypothesis that TK is involved in the cardiovascular and renal effects of high aldosterone. Kallikrein-deficient mice (TK-/-), and wild-type (WT) littermates, studied on two different genetic backgrounds, were treated with aldosterone and high-NaCl diet for 1 month. Control mice received vehicle and standard NaCl diet. Treatment induced 5- to 7 fold increase in plasma aldosterone, suppressed renin secretion, and increased urinary TK activity. In 129SvJ-C57BL/6J mice, blood pressure monitored by radiotelemetry was not different between control TK-/- and WT mice. In TK-/- mice, aldosterone induced larger increases in blood pressure than in WT mice (+47 vs. +27 mm Hg; genotype-treatment interaction, P < 0.05). Night-day difference was also exacerbated in treated TK-/- mice (P < 0.01). Moderate cardiac septal hypertrophy was observed in hypertensive animals without major change in heart function. Aldosterone-salt increased kidney weight similarly in both genotypes but induced a 2-fold increase in renal mRNA abundance of epithelial sodium channel subunits only in TK-/- mice. The hypertensive effect of TK deficiency was also documented in treated C57BL/6J mice. In this strain, aldosterone-induced hypertension was only observed in TK-/- mice (+16 mm Hg, P < 0.01). These findings show that TK deficiency exacerbates aldosterone-salt-induced hypertension. This effect may be due at least in part to enhanced sodium reabsorption in the distal nephron aggravating sodium retention. The study suggests that kallikrein plays an antihypertensive role in hyperaldosteronism. PMID- 22669898 TI - Simultaneous coronary angiography during titration of radiofrequency energy for ablation of left ventricular summit tachycardia in the 'inaccessible area'. PMID- 22669899 TI - The implementation of Integrated Disease Surveillance and Response in Uganda: a review of progress and challenges between 2001 and 2007. AB - BACKGROUND: In 2000 Uganda adopted the Integrated Disease Surveillance and Response (IDSR) strategy, which aims to create a co-ordinated approach to the collection, analysis, interpretation, use and dissemination of surveillance data for guiding decision making on public health actions. METHODS: We used a monitoring framework recommended by World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC)-Atlanta to evaluate performance of the IDSR core indicators at the national level from 2001 to 2007. To determine the performance of IDSR at district and health facility levels over a 5-year period, we compared the evaluation results of a 2004 surveillance survey with findings from a baseline assessment in 2000. We also examined national-level funding for IDSR implementation during 2000-07. RESULTS: Our findings show improvements in the performance of IDSR, including: (1) improved reporting at the district level (49% in 2001; 85% in 2007); (2) an increase and then decrease in timeliness of reporting from districts to central level; and (3) an increase in analysed data at the local level (from 10% to 47% analysing at least one target disease, P < 0.01). The case fatality rate (CFR) for two target priority diseases (cholera and meningococcal meningitis) decreased during IDSR implementation (cholera: from 7% to 2%; meningitis: from 16% to 4%), most likely due to improved outbreak response. A comparison before and after implementation showed increased funding for IDSR from government and development partners. However, funding support decreased ten-fold from the government budget of 2000/01 through to 2007/08. Per capita input for disease surveillance activities increased from US$0.0046 in 1996 99 to US$0.0215 in 2000-07. CONCLUSION: Implementation of IDSR was associated with improved surveillance and response efforts. However, decreased budgetary support from the government may be eroding these gains. Renewed efforts from government and other stakeholders are necessary to sustain and expand progress achieved through implementation of IDSR. PMID- 22669900 TI - Herpes zoster vaccine and the incidence of recurrent herpes zoster in an immunocompetent elderly population. AB - BACKGROUND: The benefit of vaccinating immunocompetent patients who have had shingles has not been examined. The study assessed the association between vaccination and the incidence of herpes zoster recurrence among persons with a recent episode of clinically diagnosed herpes zoster. METHODS: This is a matched cohort study in Kaiser Permanente Southern California. Study populations were immunocompetent elderly individuals >= 60 years old with a recent episode of herpes zoster. Incidence of recurrent herpes zoster was compared between the vaccinated and the unvaccinated matched cohorts. RESULTS: A total of 1036 vaccinated and 5180 unvaccinated members were included. On the basis of clinically confirmed cases, the incidence of recurrent herpes zoster among persons aged <70 years was 0.99 (95% confidence interval [CI], .02-5.54) and 2.20 (95% CI, 1.10-3.93) cases per 1000 person-years in the vaccinated and unvaccinated cohorts, respectively. The adjusted hazard ratio was 0.39 (95% CI, .05-4.45) among persons aged <70 years and 1.05 (95% CI, .30-3.69) among persons aged >= 70 years. CONCLUSIONS: The risk of herpes zoster recurrence following a recent initial episode is fairly low among immunocompetent adults, regardless of vaccination status. Such a low risk suggests that one should evaluate the necessity of immediately vaccinating immunocompetent patients who had a recent herpes zoster episode. PMID- 22669901 TI - Molecular characterization of an adaptive response to alkylating agents in the opportunistic pathogen Aspergillus fumigatus. AB - An adaptive response to alkylating agents based upon the conformational change of a methylphosphotriester (MPT) DNA repair protein to a transcriptional activator has been demonstrated in a number of bacterial species, but this mechanism appears largely absent from eukaryotes. Here, we demonstrate that the human pathogen Aspergillus fumigatus elicits an adaptive response to sub-lethal doses of the mono-functional alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). We have identified genes that encode MPT and O(6)-alkylguanine DNA alkyltransferase (AGT) DNA repair proteins; deletions of either of these genes abolish the adaptive response and sensitize the organism to MNNG. In vitro DNA repair assays confirm the ability of MPT and AGT to repair methylphosphotriester and O(6)-methylguanine lesions respectively. In eukaryotes, the MPT protein is confined to a select group of fungal species, some of which are major mammalian and plant pathogens. The evolutionary origin of the adaptive response is bacterial and rooted within the Firmicutes phylum. Inter-kingdom horizontal gene transfer between Firmicutes and Ascomycete ancestors introduced the adaptive response into the Fungal kingdom. Our data constitute the first detailed characterization of the molecular mechanism of the adaptive response in a lower eukaryote and has applications for development of novel fungal therapeutics targeting this DNA repair system. PMID- 22669902 TI - HomozygosityMapper2012--bridging the gap between homozygosity mapping and deep sequencing. AB - Homozygosity mapping is a common method to map recessive traits in consanguineous families. To facilitate these analyses, we have developed HomozygosityMapper, a web-based approach to homozygosity mapping. HomozygosityMapper allows researchers to directly upload the genotype files produced by the major genotyping platforms as well as deep sequencing data. It detects stretches of homozygosity shared by the affected individuals and displays them graphically. Users can interactively inspect the underlying genotypes, manually refine these regions and eventually submit them to our candidate gene search engine GeneDistiller to identify the most promising candidate genes. Here, we present the new version of HomozygosityMapper. The most striking new feature is the support of Next Generation Sequencing *.vcf files as input. Upon users' requests, we have implemented the analysis of common experimental rodents as well as of important farm animals. Furthermore, we have extended the options for single families and loss of heterozygosity studies. Another new feature is the export of *.bed files for targeted enrichment of the potential disease regions for deep sequencing strategies. HomozygosityMapper also generates files for conventional linkage analyses which are already restricted to the possible disease regions, hence superseding CPU-intensive genome-wide analyses. HomozygosityMapper is freely available at http://www.homozygositymapper.org/. PMID- 22669903 TI - High-resolution structures of two complexes between thrombin and thrombin-binding aptamer shed light on the role of cations in the aptamer inhibitory activity. AB - The G-quadruplex architecture is a peculiar structure adopted by guanine-rich oligonucleotidic sequences, and, in particular, by several aptamers, including the thrombin-binding aptamer (TBA) that has the highest inhibitory activity against human alpha-thrombin. A crucial role in determining structure, stability and biological properties of G-quadruplexes is played by ions. In the case of TBA, K(+) ions cause an enhancement of the aptamer clotting inhibitory activity. A detailed picture of the interactions of TBA with the protein and with the ions is still lacking, despite the importance of this aptamer in biomedical field for detection and inhibition of alpha-thrombin. Here, we fill this gap by presenting a high-resolution crystallographic structural characterization of the thrombin TBA complex formed in the presence of Na(+) or K(+) and a circular dichroism study of the structural stability of the aptamer both free and complexed with alpha-thrombin, in the presence of the two ionic species. The results indicate that the different effects exerted by Na(+) and K(+) on the inhibitory activity of TBA are related to a subtle perturbation of a few key interactions at the protein-aptamer interface. The present data, in combination with those previously obtained on the complex between alpha-thrombin and a modified aptamer, may allow the design of new TBA variants with a pharmacological performance enhancement. PMID- 22669904 TI - Single-molecule microscopy reveals new insights into nucleotide selection by DNA polymerase I. AB - The mechanism by which DNA polymerases achieve their extraordinary accuracy has been intensely studied because of the linkage between this process and mutagenesis and carcinogenesis. Here, we have used single-molecule fluorescence microscopy to study the process of nucleotide selection and exonuclease action. Our results show that the binding of Escherichia coli DNA polymerase I (Klenow fragment) to a primer-template is stabilized by the presence of the next correct dNTP, even in the presence of a large excess of the other dNTPs and rNTPs. These results are consistent with a model where nucleotide selection occurs in the open complex prior to the formation of a closed ternary complex. Our assay can also distinguish between primer binding to the polymerase or exonuclease domain and, contrary to ensemble-averaged studies, we find that stable exonuclease binding only occurs with a mismatched primer terminus. PMID- 22669905 TI - PSC: protein surface classification. AB - We recently proposed to classify proteins by their functional surfaces. Using the structural attributes of functional surfaces, we inferred the pairwise relationships of proteins and constructed an expandable database of protein surface classification (PSC). As the functional surface(s) of a protein is the local region where the protein performs its function, our classification may reflect the functional relationships among proteins. Currently, PSC contains a library of 1974 surface types that include 25,857 functional surfaces identified from 24,170 bound structures. The search tool in PSC empowers users to explore related surfaces that share similar local structures and core functions. Each functional surface is characterized by structural attributes, which are geometric, physicochemical or evolutionary features. The attributes have been normalized as descriptors and integrated to produce a profile for each functional surface in PSC. In addition, binding ligands are recorded for comparisons among homologs. PSC allows users to exploit related binding surfaces to reveal the changes in functionally important residues on homologs that have led to functional divergence during evolution. The substitutions at the key residues of a spatial pattern may determine the functional evolution of a protein. In PSC (http://pocket.uchicago.edu/psc/), a pool of changes in residues on similar functional surfaces is provided. PMID- 22669906 TI - NMSim web server: integrated approach for normal mode-based geometric simulations of biologically relevant conformational transitions in proteins. AB - The NMSim web server implements a three-step approach for multiscale modeling of protein conformational changes. First, the protein structure is coarse-grained using the FIRST software. Second, a rigid cluster normal-mode analysis provides low-frequency normal modes. Third, these modes are used to extend the recently introduced idea of constrained geometric simulations by biasing backbone motions of the protein, whereas side chain motions are biased toward favorable rotamer states (NMSim). The generated structures are iteratively corrected regarding steric clashes and stereochemical constraint violations. The approach allows performing three simulation types: unbiased exploration of conformational space; pathway generation by a targeted simulation; and radius of gyration-guided simulation. On a data set of proteins with experimentally observed conformational changes, the NMSim approach has been shown to be a computationally efficient alternative to molecular dynamics simulations for conformational sampling of proteins. The generated conformations and pathways of conformational transitions can serve as input to docking approaches or more sophisticated sampling techniques. The web server output is a trajectory of generated conformations, Jmol representations of the coarse-graining and a subset of the trajectory and data plots of structural analyses. The NMSim webserver, accessible at http://www.nmsim.de, is free and open to all users with no login requirement. PMID- 22669907 TI - Cscan: finding common regulators of a set of genes by using a collection of genome-wide ChIP-seq datasets. AB - The regulation of transcription of eukaryotic genes is a very complex process, which involves interactions between transcription factors (TFs) and DNA, as well as other epigenetic factors like histone modifications, DNA methylation, and so on, which nowadays can be studied and characterized with techniques like ChIP Seq. Cscan is a web resource that includes a large collection of genome-wide ChIP Seq experiments performed on TFs, histone modifications, RNA polymerases and others. Enriched peak regions from the ChIP-Seq experiments are crossed with the genomic coordinates of a set of input genes, to identify which of the experiments present a statistically significant number of peaks within the input genes' loci. The input can be a cluster of co-expressed genes, or any other set of genes sharing a common regulatory profile. Users can thus single out which TFs are likely to be common regulators of the genes, and their respective correlations. Also, by examining results on promoter activation, transcription, histone modifications, polymerase binding and so on, users can investigate the effect of the TFs (activation or repression of transcription) as well as of the cell or tissue specificity of the genes' regulation and expression. The web interface is free for use, and there is no login requirement. Available at: http://www.beaconlab.it/cscan. PMID- 22669908 TI - Quantum.Ligand.Dock: protein-ligand docking with quantum entanglement refinement on a GPU system. AB - Quantum.Ligand.Dock (protein-ligand docking with graphic processing unit (GPU) quantum entanglement refinement on a GPU system) is an original modern method for in silico prediction of protein-ligand interactions via high-performance docking code. The main flavour of our approach is a combination of fast search with a special account for overlooked physical interactions. On the one hand, we take care of self-consistency and proton equilibria mutual effects of docking partners. On the other hand, Quantum.Ligand.Dock is the the only docking server offering such a subtle supplement to protein docking algorithms as quantum entanglement contributions. The motivation for development and proposition of the method to the community hinges upon two arguments-the fundamental importance of quantum entanglement contribution in molecular interaction and the realistic possibility to implement it by the availability of supercomputing power. The implementation of sophisticated quantum methods is made possible by parallelization at several bottlenecks on a GPU supercomputer. The high performance implementation will be of use for large-scale virtual screening projects, structural bioinformatics, systems biology and fundamental research in understanding protein-ligand recognition. The design of the interface is focused on feasibility and ease of use. Protein and ligand molecule structures are supposed to be submitted as atomic coordinate files in PDB format. A customization section is offered for addition of user-specified charges, extra ionogenic groups with intrinsic pK(a) values or fixed ions. Final predicted complexes are ranked according to obtained scores and provided in PDB format as well as interactive visualization in a molecular viewer. Quantum.Ligand.Dock server can be accessed at http://87.116.85.141/LigandDock.html. PMID- 22669909 TI - VIGOR extended to annotate genomes for additional 12 different viruses. AB - A gene prediction program, VIGOR (Viral Genome ORF Reader), was developed at J. Craig Venter Institute in 2010 and has been successfully performing gene calling in coronavirus, influenza, rhinovirus and rotavirus for projects at the Genome Sequencing Center for Infectious Diseases. VIGOR uses sequence similarity search against custom protein databases to identify protein coding regions, start and stop codons and other gene features. Ribonucleicacid editing and other features are accurately identified based on sequence similarity and signature residues. VIGOR produces four output files: a gene prediction file, a complementary DNA file, an alignment file, and a gene feature table file. The gene feature table can be used to create GenBank submission. VIGOR takes a single input: viral genomic sequences in FASTA format. VIGOR has been extended to predict genes for 12 viruses: measles virus, mumps virus, rubella virus, respiratory syncytial virus, alphavirus and Venezuelan equine encephalitis virus, norovirus, metapneumovirus, yellow fever virus, Japanese encephalitis virus, parainfluenza virus and Sendai virus. VIGOR accurately detects the complex gene features like ribonucleicacid editing, stop codon leakage and ribosomal shunting. Precisely identifying the mat_peptide cleavage for some viruses is a built-in feature of VIGOR. The gene predictions for these viruses have been evaluated by testing from 27 to 240 genomes from GenBank. PMID- 22669910 TI - MAGNET: MicroArray Gene expression and Network Evaluation Toolkit. AB - MicroArray Gene expression and Network Evaluation Toolkit (MAGNET) is a web-based application that provides tools to generate and score both protein-protein interaction networks and coexpression networks. MAGNET integrates user-provided experimental measurements with high-throughput proteomic datasets, generating weighted gene-gene and protein-protein interaction networks. MAGNET allows users to weight edges of protein-protein interaction networks using a logistic regression model integrating tissue-specific gene expression data, sub-cellular localization data, co-clustering of interacting proteins and the number of observations of the interaction. This provides a way to quantitatively measure the plausibility of interactions in protein-protein interaction networks given protein/gene expression measurements. Secondly, MAGNET generates filtered coexpression networks, where genes are represented as nodes, and their correlations are represented with edges. Overall, MAGNET provides researchers with a new framework with which to analyze and generate gene-gene and protein protein interaction networks, based on both the user's own data and publicly available -omics datasets. The freely available service and documentation can be accessed at http://gurkan.case.edu/software or http://magnet.case.edu. PMID- 22669911 TI - Quantitative proteomics profiling of the poly(ADP-ribose)-related response to genotoxic stress. AB - Upon DNA damage induction, DNA-dependent poly(ADP-ribose) polymerases (PARPs) synthesize an anionic poly(ADP-ribose) (pADPr) scaffold to which several proteins bind with the subsequent formation of pADPr-associated multiprotein complexes. We have used a combination of affinity-purification methods and proteomics approaches to isolate these complexes and assess protein dynamics with respect to pADPr metabolism. As a first approach, we developed a substrate trapping strategy by which we demonstrate that a catalytically inactive Poly(ADP-ribose) glycohydrolase (PARG) mutant can act as a physiologically selective bait for the isolation of specific pADPr-binding proteins through its macrodomain-like domain. In addition to antibody-mediated affinity-purification methods, we used a pADPr macrodomain affinity resin to recover pADPr-binding proteins and their complexes. Second, we designed a time course experiment to explore the changes in the composition of pADPr-containing multiprotein complexes in response to alkylating DNA damage-mediated PARP activation. Spectral count clustering based on GeLC MS/MS analysis was complemented with further analyses using high precision quantitative proteomics through isobaric tag for relative and absolute quantitation (iTRAQ)- and Stable isotope labeling by amino acids in cell culture (SILAC)-based proteomics. Here, we present a valuable resource in the interpretation of systems biology of the DNA damage response network in the context of poly(ADP-ribosyl)ation and provide a basis for subsequent investigations of pADPr-binding protein candidates. PMID- 22669913 TI - CMWeb: an interactive on-line tool for analysing residue-residue contacts and contact prediction methods. AB - A contact map is a 2D derivative of the 3D structure of proteins, containing various residue-residue (RR) contacts within the structure. Contact maps can be used for the reconstruction of structure with high accuracy and can be predicted from the amino acid sequence. Therefore understanding the various properties of contact maps is an important step in protein structure prediction. For investigating basic properties of contact formation and contact clusters we set up an integrated system called Contact Map Web Viewer, or CMWeb for short. The server can be used to visualize contact maps, to link contacts and to show them both in 3D structures and in multiple sequence alignments and to calculate various statistics on contacts. Moreover, we have implemented five contact prediction methods in the CMWeb server to visualize the predicted and real RR contacts in one contact map. The results of other RR contact prediction methods can be uploaded as a benchmark test onto the server as well. All of these functionality is behind a web server, thus for using our application only a Java capable web browser is needed, no further program installation is required. The CMWeb is freely accessible at http://cmweb.enzim.hu. PMID- 22669912 TI - KOSMOS: a universal morph server for nucleic acids, proteins and their complexes. AB - KOSMOS is the first online morph server to be able to address the structural dynamics of DNA/RNA, proteins and even their complexes, such as ribosomes. The key functions of KOSMOS are the harmonic and anharmonic analyses of macromolecules. In the harmonic analysis, normal mode analysis (NMA) based on an elastic network model (ENM) is performed, yielding vibrational modes and B-factor calculations, which provide insight into the potential biological functions of macromolecules based on their structural features. Anharmonic analysis involving elastic network interpolation (ENI) is used to generate plausible transition pathways between two given conformations by optimizing a topology-oriented cost function that guarantees a smooth transition without steric clashes. The quality of the computed pathways is evaluated based on their various facets, including topology, energy cost and compatibility with the NMA results. There are also two unique features of KOSMOS that distinguish it from other morph servers: (i) the versatility in the coarse-graining methods and (ii) the various connection rules in the ENM. The models enable us to analyze macromolecular dynamics with the maximum degrees of freedom by combining a variety of ENMs from full-atom to coarse-grained, backbone and hybrid models with one connection rule, such as distance-cutoff, number-cutoff or chemical-cutoff. KOSMOS is available at http://bioengineering.skku.ac.kr/kosmos. PMID- 22669914 TI - Piloting the use of indigenous methods to prevent Nipah virus infection by interrupting bats' access to date palm sap in Bangladesh. AB - People in Bangladesh frequently drink fresh date palm sap. Fruit bats (Pteropus giganteus) also drink raw sap and may contaminate the sap by shedding Nipah virus through saliva and urine. In a previous study we identified two indigenous methods to prevent bats accessing the sap, bamboo skirts and lime (calcium carbonate). We conducted a pilot study to assess the acceptability of these two methods among sap harvesters. We used interactive community meetings and group discussions to encourage all the sap harvesters (n = 12) from a village to use either bamboo skirts or lime smear that some of them (n = 4) prepared and applied. We measured the preparation and application time and calculated the cost of bamboo skirts. We conducted interviews after the use of each method. The sap harvesters found skirts effective in preventing bats from accessing sap. They were sceptical that lime would be effective as the lime was washed away by the sap flow. Preparation of the skirt took ~105 min. The application of each method took ~1 min. The cost of the bamboo skirt is minimal because bamboo is widely available and they made the skirts with pieces of used bamboo. The bamboo skirt method appeared practical and affordable to the sap harvesters. Further studies should explore its ability to prevent bats from accessing date palm sap and assess if its use produces more or better quality sap, which would provide further incentives to make it more acceptable for its regular use. PMID- 22669915 TI - Children as agents of their own health: exploratory analysis of child discourse in Spain. AB - The promotion of children's decision-making is one of the principles of health promoting schools, and the empowerment of children means that they are enabled to influence their lifestyles and living conditions. The aim of this study was to find out the suggestions of Spanish school pupils in Year 3 and Year 6 of primary education to promote their own health and the health of the people closer to them, through their ideas about health. We analyse the discourse on health in the school environment from focus groups of primary school pupils aged around 8 and 12 of five schools in the town of Alicante (Spain). The groups were organized according to the type of school (public, private), the socioeconomic status of the neighbourhood (residential, working-class) and gender (single-sex, mixed groups) to ensure both the highest intergroup diversity and intra-group homogeneity. The findings show that primary school pupils have a wide and diverse notion of health. The application of the focus group technique has proved useful in eliciting information from groups of primary school pupils, and involving students in health-promoting programmes because it allows them to identify the social and interpersonal determinants of health. There is a firm basis to consider school pupils as health agents, particularly regarding interventions within the school environment itself. With the support of teachers, it is possible to train school pupils as community health agents, and increase their control over their own health. PMID- 22669916 TI - ACAT2 and ABCG5/G8 are both required for efficient cholesterol absorption in mice: evidence from thoracic lymph duct cannulation. AB - The metabolic fate of newly absorbed cholesterol and phytosterol is orchestrated through adenosine triphosphate-binding cassette transporter G5 and G8 heterodimer (G5G8), and acyl CoA:cholesterol acyltransferase 2 (ACAT2). We hypothesized that intestinal G5G8 limits sterol absorption by reducing substrate availability for ACAT2 esterification and have attempted to define the roles of these two factors using gene deletion studies in mice. Male ACAT2(-/-), G5G8(-/-), ACAT2(-/-)G5G8( /-) (DKO), and wild-type (WT) control mice were fed a diet with 20% of energy as palm oil and 0.2% (w/w) cholesterol. Sterol absorption efficiency was directly measured by monitoring the appearance of [(3)H]sitosterol and [(14)C]cholesterol tracers in lymph after thoracic lymph duct cannulation. The average percentage (+/- SEM) absorption of [(14)C]cholesterol after 8 h of lymph collection was 40.55 +/- 0.76%, 19.41 +/- 1.52%, 32.13 +/- 1.60%, and 21.27 +/- 1.35% for WT, ACAT2(-/-), G5G8(-/-), and DKO mice, respectively. [(3)H]sitosterol absorption was <2% in WT and ACAT2(-/-) mice, whereas it was up to 6.8% in G5G8(-/-) and DKO mice. G5G8(-/-) mice also produced chylomicrons with ~70% less cholesterol ester mass than WT mice. In contrast to expectations, the data demonstrated that the absence of G5G8 led to decreased intestinal cholesterol esterification and reduced cholesterol transport efficiency. Intestinal G5G8 appeared to limit the absorption of phytosterols; ACAT2 more efficiently esterified cholesterol than phytosterols. The data indicate that handling of sterols by the intestine involves both G5G8 and ACAT2 but that an additional factor (possibly Niemann-Pick C1-like 1) may be key in determining absorption efficiency. PMID- 22669917 TI - Evolution of substrate specificity for the bile salt transporter ASBT (SLC10A2). AB - The apical Na(+)-dependent bile salt transporter (ASBT/SLC10A2) is essential for maintaining the enterohepatic circulation of bile salts. It is not known when Slc10a2 evolved as a bile salt transporter or how it adapted to substantial changes in bile salt structure during evolution. We characterized ASBT orthologs from two primitive vertebrates, the lamprey that utilizes early 5alpha-bile alcohols and the skate that utilizes structurally different 5beta-bile alcohols, and compared substrate specificity with ASBT from humans who utilize modern 5beta bile acids. Everted gut sacs of skate but not the more primitive lamprey transported (3)H-taurocholic acid (TCA), a modern 5beta-bile acid. However, molecular cloning identified ASBT orthologs from both species. Cell-based assays using recombinant ASBT/Asbt's indicate that lamprey Asbt has high affinity for 5alpha-bile alcohols, low affinity for 5beta-bile alcohols, and lacks affinity for TCA, whereas skate Asbt showed high affinity for 5alpha- and 5beta-bile alcohols but low affinity for TCA. In contrast, human ASBT demonstrated high affinity for all three bile salt types. These findings suggest that ASBT evolved from the earliest vertebrates by gaining affinity for modern bile salts while retaining affinity for older bile salts. Also, our results indicate that the bile salt enterohepatic circulation is conserved throughout vertebrate evolution. PMID- 22669918 TI - Combined deletion of SCD1 from adipose tissue and liver does not protect mice from obesity. AB - Stearoyl-CoA desaturase 1 (SCD1) catalyzes the synthesis of monounsaturated fatty acids (MUFA) from saturated FA. Mice with whole-body or skin-specific deletion of SCD1 are resistant to obesity. Here, we show that mice lacking SCD1 in adipose and/or liver are not protected from either genetic- (agouti; A(y)/a) or diet induced obesity (DIO) despite a robust reduction in SCD1 MUFA products in both subcutaneous and epididymal white adipose tissue. Adipose SCD1 deletion had no effect on glucose or insulin tolerance or on hepatic triglyceride (TG) accumulation. Interestingly, lack of SCD1 from liver lowered the MUFA levels of adipose tissue and vice versa, as reflected by the changes in FA composition. Simultaneous deletion of SCD1 from liver and adipose resulted in a synergistic lowering of tissue MUFA levels, especially in the A(y)/a model in which glucose tolerance was also improved. Lastly, we found that liver and plasma TG show nearly identical genotype-dependent differences in FA composition, indicating that FA composition of plasma TG is predictive for hepatic SCD1 activity and TG FA composition. The current study suggests that SCD1 deletion from adipose and/or liver is insufficient to elicit protection from obesity, but it supports the existence of extensive lipid cross-talk between liver and adipose tissue. PMID- 22669920 TI - An occult filarial infection presenting as chyluria with proteinuria: a case report and review of literature. AB - Chyluria is the passage of chyle into urine, and develops as a result of communication between the lymphatic system and the urinary system. It is an unusual manifestation of lymphatic filariasis reported mainly from South Asian countries. We report the case of a 38-year-old man from an endemic area who presented with passage of milky urine. Physical examination did not reveal any lymphadenopathy or lymph oedema. Urine tests revealed nephrotic range proteinuria. A 99m technetium sulphur colloid lymphoscintigraphy confirmed connection between lymphatic vessels and the urinary tract. Predominant chyluria with no overt lymphatic filariasis remains an enigma. PMID- 22669919 TI - A pelvic mass on ultrasonography and high human chorionic gonadotropin level: not always an ectopic pregnancy. AB - A 24-year-old patient with 7-week amenorrhoea consulted for vaginal bleeding without abdominal pain. Ultrasonography revealed a 7 * 4 cm solid right pelvic mass. There was no visible intrauterine gestational sac. The serum beta-human chorionic gonadotropin (beta-hCG) level was 11 998 IU/l. Emergency laparoscopy was performed for a presumptive diagnosis of ectopic pregnancy. At laparoscopy, the right ovary was enlarged with a non-haemorrhagic 7 * 4 cm solid lesion, which was resected. The histological diagnosis was a dysgerminoma with immunohistochemistry showing nests of syncytiotrophoblastic cells, which were the origin of the hCG production. There was no pregnancy, either intrauterine or ectopic. There was no evidence of metastasis from the dysgerminoma on the positron-emission tomography scanner. The patient underwent a second procedure for surgical staging of this ovarian germ-cell tumour. This ovarian dysgerminoma was staged FIGO 1A, and the patient did not receive adjuvant therapy. There was no recurrence at the last 8-month follow-up. PMID- 22669921 TI - Resolution of severe hepato-pulmonary syndrome following transjugular portosystemic shunt procedure. AB - The hepato-pulmonary syndrome (HPS) is a relatively common complication of hepatic disease that leads to hypoxaemia and dyspnoea secondary to pulmonary shunting. A number of pharmacological therapies have been trialled, yet liver transplantation remains the only definitive treatment. The use of a transjugular intrahepatic portosystemic shunt (TIPS) to reduce portal hypertension and improve oxygenation remains controversial in HPS due to the lack of large clinical series or randomised controlled trials. We present a case of HPS successfully treated with TIPS and review the relevant literature. PMID- 22669922 TI - Unusual association of eclamptic encephalopathy and Japanese encephalitis. AB - Eclampsia is one of the hypertensive disorders of pregnancy causing considerable maternal morbidity and mortality. It is more common in developing nations, where access to adequate obstetric care is limited to a small population. Eclampsia is clinically characterised by encephalopathy, seizures, headache and cortical blindness and occurs in the setting of pre-eclampsia that comprises hypertension, proteinuria and peripheral oedema. Japanese encephalitis has emerged as a serious neurological disorder in South East Asian countries. In this case report, we highlight the unusual association of eclamptic encephalopathy and Japanese encephalitis in a patient belonging to northern India. This combination of illnesses caused diagnostic difficulty and delayed hospitalisation. A high index of suspicion is required in the endemic zone of Japanese encephalitis if the expected results are lacking in patients with eclampsia. PMID- 22669923 TI - A rare case of basilar impression. AB - A teenage girl presented with progressively worsening neck and occipital pain since 8 months ago that was associated with restriction of neck movements, low to moderate grade fever, anorexia and weight loss followed by gradually progressive quadriparesis since 3 months ago. Neurological examination revealed spastic quadriparesis without cranial nerve palsy. MRI of the cervical spine revealed prevertebral and paravertebral abscess from clivus to C2/C3 level, which extended into the anterior epidural space at C1-C3 level, causing atlantoaxial dislocation. There was evidence of basilar invagination. The dislocated dens caused compression over the cervicomedullary junction. On this basis, a diagnosis of craniovertebral junction Pott's disease was made. The patient was given neck immobilisation with cervical collar, and antitubercular treatment was started. She showed significant improvement in her neurological deficit during follow-up. PMID- 22669924 TI - Staphylococcus aureus mitral valve endocarditis due to heel decubitus ulcer. PMID- 22669925 TI - Rectus sheath haematoma. PMID- 22669926 TI - Previous iodinated contrast anaphylaxis in blunt abdominal trauma: management options. AB - A 34-year-old man presented with significant intra-abdominal and orthopaedic injuries following a high-speed motorbike crash. The man had a history of an anaphylactic reaction to iodine. As a result, the gold standard CT of the abdomen with contrast was unable to be performed to ascertain the exact nature of the intra-abdominal injuries. After stabilisation, an MRI of the abdomen was performed which localised the injuries. The previous contrast anaphylaxis delayed full assessment of the patient and subsequent management. This case discusses the current literature and the management guidelines in a patient with previous anaphylaxis to contrast. PMID- 22669927 TI - Seizures and postictal stupor in a patient with uncontrolled Graves' hyperthyroidism. AB - A 16-year-old girl with a history of Graves' disease presented with two episodes of generalised tonic-clonic seizures, necessitating intensive care admission. Laboratory examination demonstrated a suppressed thyroid-stimulating hormone level with dramatically elevated free triiodothyronine, free thyroxine and thyroid-stimulating immunoglobulins. Cerebrospinal fluid analysis showed oligoclonal banding in the absence of pleocytosis, thyroid peroxidase antibodies or infection. Neuroimaging revealed the presence of a congenital arachnoid cyst in the right temporal lobe. Despite restoration of euthyroidism and administration of antiepileptic and antiviral drugs, neurological features persisted. Subsequently, intravenous corticoids were administered to exclude the contribution of an underlying autoimmune encephalopathy. The patient gradually recovered and, in retrospect, elevated serum N-methyl-D-aspartic acid-receptor (NMDA-R) antibodies were detected. Although this patient presented with an intracerebral arachnoid cyst that can act epileptogenic per se, the combination of prolonged postictal encephalopathy with unresponsiveness to antiepileptic measures, absence of focal epileptiform activity on EEG, response to corticoids and serum NMDA-R antibody positivity favours the diagnosis of autoimmune NMDA-R encephalitis in this case. PMID- 22669928 TI - A dilemma of fibrous dysplasia versus chronic osteomyelitis of the clavicle. AB - An 11-year-old child presented to the emergency department in 2005 with episodes of pain in his right clavicle. No history of trauma was noted and he was systemically well with no clinical signs of acute inflammation. He was extensively investigated and a diagnosis of fibrous dysplasia of the right clavicle was reached on histology. He developed periodic relapses of pain in the clavicle. He has been followed up since 2005, his most recent follow-up being in November 2011. The clinical dilemma of fibrous dysplasia versus chronic osteomyelitis is illustrated by highlighting this case. PMID- 22669929 TI - Medical cause of compartment syndrome: a fatal case of Clostridium septicum. AB - A 57-year-old woman with non-Hodgkin's lymphoma presented to the emergency department with febrile neutropaenia. She complained of fever and malaise and had a normal physical examination. Ten hours later, she developed worsening right leg pain that required escalating doses of morphine. Her physical examination remained unremarkable. Owing to the increasing pain in her leg, an x-ray was performed which revealed subcutaneous emphysema. She subsequently developed numbness over her right leg and, then, 21 h after admission the leg became cold and ischaemic. Haemorrhagic bullae and bruising began to form and crepitus was palpated. She was taken to the operating room where debridement was attempted, but the surgeons found deep and extensive tissue necrosis. She was transferred to the intensive care unit for a trial of medical therapy and eventual palliation. The pathology revealed severe myonecrosis secondary to Clostridium septicum. She expired 36 h after presentation. PMID- 22669930 TI - Chondrosarcoma of the nasal septum. AB - Chondrosarcoma of the nasal septum is a rare malignancy. When it occurs, early diagnosis is difficult because patients generally present with common, non specific sinonasal complaints. This is the report of a 62-year-old woman who presented with a 1-month history of nasal obstruction, headache and anosmia. Nasal endoscopy showed a nasal mass obstructing both nasal cavities not separable from the septum. A wedge biopsy of the nasal mass was taken. Histopathology was suggestive of chondrosarcoma. The tumour was removed by an endoscopic approach. The clinical presentation, diagnosis and treatment of this case as well as a review of the literature are discussed. PMID- 22669931 TI - Usefulness of Palliative Prognostic Index for patient with advanced cancer in home care setting. AB - AIMS: This study aimed to clarify the accuracy of the Palliative Prognostic Index (PPI) for advanced cancer patients in home care settings. METHOD: The study included 65 advanced cancer patients who received home visiting services between April 2007 and June 2009, and who died at home or in the hospital. Using the medical records from initial home visits, we retrospectively calculated PPI scores along with sensitivity and specificity. RESULTS: For 3- and 6-week survival, prognostic prediction demonstrated respective sensitivities of 55% and 63%, and specificities of 79% and 77%. CONCLUSION: The sensitivity of the PPI for advanced cancer patients in home care settings was lower than reported for those in palliative care units. Development of prognostic tools suitable for home care settings is needed. PMID- 22669932 TI - Increasing access--a qualitative study of homelessness and palliative care in a major urban center. AB - Rates of morbidity and mortality are significantly higher in homeless populations. Homeless people experience many barriers to receive adequate palliative care. This qualitative study examines how a major urban city's palliative care resources can be improved to increase access and better serve the homeless. Audiotaped interviews were preformed with 7 homeless care providers in Toronto, Canada, and their transcripts were analyzed using thematic analysis. The findings of the study suggest that in order to increase access and to serve the city's terminally ill homeless better, the following 4 areas must be addressed: (1) increasing positive interaction between the health care system and the homeless, (2) training staff to deal with the unique issues confronting the homeless, (3) providing patient-centered care, and (4) diversifying the methods of delivery. PMID- 22669933 TI - Evaluating the effectiveness of CPR for in-hospital cardiac arrest. AB - Cardiopulmonary resuscitation (CPR) is one of the most commonly performed medical interventions. However, the true effectiveness of CPR remains unknown as it presents significant challenges for evaluation and research. Many resuscitation practices are driven by nonquantitative reasoning and may not be evidence based. Several studies have been published on survival after in-hospital CPR. However, the reported survival rates from one hospital to another vary significantly due to a number of reasons such as type of hospital, presence of specialized cardiac units, patient demographics, differences in inclusion criteria, outcome definitions and so on. Further research is indicated to evaluate the true effectiveness of CPR for in-hospital cardiac arrest. PMID- 22669934 TI - Noncancer palliative care: the lost pieces in an acute care setting in Taiwan. AB - Little is known about the picture of patients receiving palliative care in the acute care setting. The study was conducted in a medical center in Taiwan. Cancer palliative care (CPC) was performed for terminal do-not-resuscitate (DNR) patients with advanced cancers. Noncancer palliative care (NCPC) was performed for DNR patients who did not fulfill the criteria of CPC. Of the 1379 consecutive admissions, 258 patients were identified, with 193 (74.8%) requiring NCPC and 65 (25.2%) requiring CPC. The NCPC patients were older and had lower Charlson comorbidity index (2.6 vs 8.6, P < .001) than CPC patients and had poorer consciousness and more organ failure than CPC patients when recognized. Many noncancer patients without access to specialist palliative care services were treated in the acute care setting with delayed recognition. PMID- 22669935 TI - Provider approaches to palliative dyspnea assessment: implications for informatics-based clinical tools. AB - AIM: To understand provider practices around dyspnea assessment to inform the development of an electronic medical record (EMR)-based dyspnea assessment module in an inpatient palliative care consultation template. DESIGN: Qualitative analysis of palliative care provider interviews. RESULTS: Three themes emerged: (1) integration of patient self-report of breathlessness with a clinical observation of dyspnea; (2) identification of patients for dyspnea assessment based on perceived patient need; and (3) variability in preferences for and use of existing severity scales for dyspnea. CONCLUSIONS: The assessment approaches described by providers underscore the challenge of developing an informatics tool that supports the natural clinical experience and facilitates standardized care. The complexity of the dyspnea assessment process and variation in provider practices necessitate a level of flexibility and choice to be built into a computer-based tool. PMID- 22669936 TI - Latino values in the context of palliative care: illustrative cases from the Family Focused Grief Therapy trial. AB - BACKGROUND: Clinicians meet a variety of ethnicities among patients and families in hospice programs. This article focuses on Latino families. METHODS: Within a controlled trial of family therapy in the context of palliative care, 17 families identified as Hispanic. Five were examined qualitatively herein. RESULTS: A synopsis of each family's narrative is presented here. Patterns of strong family loyalty (Familismo), the gender roles of Machismo and Marianismo, the importance of family tradition, expectations about caregiving, and the place of faith and religion emerged as prominent and able potentially to impact on the therapy. CONCLUSIONS: Family therapists need to be thoughtful about cultural issues as they strive to support families. PMID- 22669937 TI - Continuous subcutaneous infusion of compound oxycodone for the relief of dyspnea in patients with terminally ill cancer: a retrospective study. AB - Pain and dyspnea are the most prevalent and distressing symptoms in patients with terminally ill cancer. Evidences have accumulated for the effects of morphine on dyspnea, whereas little is known about the effects of oxycodone on dyspnea. We investigated the effectiveness of oxycodone for dyspnea in patients with terminally ill cancer. The injectable form of compound oxycodone (iOC) containing hydrocotarnine was administered continuously via subcutaneous route. We administered iOC to 136 patients. The effect on dyspnea was less conspicuous than pain, yet iOC was effective for dyspnea with varying degrees. None of the adverse effects observed were serious. These results suggest that continuous subcutaneous administration of oxycodone could be one of the reasonable alternatives in the management of dyspnea in patients with terminally ill cancer. PMID- 22669938 TI - Minimizing human error in radiopharmaceutical preparation and administration via a bar code-enhanced nuclear pharmacy management system. AB - The objective of this project was to ensure correct radiopharmaceutical administration through the use of a bar code system that links patient and drug profiles with on-site information management systems. This new combined system would minimize the amount of manual human manipulation, which has proven to be a primary source of error. The most common reason for dosing errors is improper patient identification when a dose is obtained from the nuclear pharmacy or when a dose is administered. A standardized electronic transfer of information from radiopharmaceutical preparation to injection will further reduce the risk of misadministration. METHODS: Value stream maps showing the flow of the patient dose information, as well as potential points of human error, were developed. Next, a future-state map was created that included proposed corrections for the most common critical sites of error. Transitioning the current process to the future state will require solutions that address these sites. To optimize the future-state process, a bar code system that links the on-site radiology management system with the nuclear pharmacy management system was proposed. A bar coded wristband connects the patient directly to the electronic information systems. RESULTS: The bar code-enhanced process linking the patient dose with the electronic information reduces the number of crucial points for human error and provides a framework to ensure that the prepared dose reaches the correct patient. Although the proposed flowchart is designed for a site with an in-house central nuclear pharmacy, much of the framework could be applied by nuclear medicine facilities using unit doses. CONCLUSION: An electronic connection between information management systems to allow the tracking of a radiopharmaceutical from preparation to administration can be a useful tool in preventing the mistakes that are an unfortunate reality for any facility. PMID- 22669939 TI - Thermodynamic dissection of the intrinsically disordered N-terminal domain of human glucocorticoid receptor. AB - Intrinsically disordered (ID) sequence segments are abundant in cell signaling proteins and transcription factors. Because ID regions commonly fold as part of their intracellular function, it is crucial to understand the folded states as well as the transitions between the unfolded and folded states. Specifically, it is important to determine 1) whether large ID segments contain different thermodynamically and/or functionally distinct regions, 2) whether any ID regions fold upon activation, 3) the degree of coupling between the different ID regions, and 4) whether the stability of ID domains is a determinant of function. In this study, we thermodynamically characterized the full-length ID N-terminal domain (NTD) of human glucocorticoid receptor (GR) and two of its naturally occurring translational isoforms. The protective osmolyte trimethylamine N-oxide (TMAO) was used to induce folding transitions. Each of the three NTD isoforms was found to undergo a cooperative folding transition that is thermodynamically indistinguishable (based on m-values) from that of a globular protein of similar size. The extrapolated stabilities for the NTD isoforms showed clear correlation with the known activities of their corresponding GR translational isoforms. The data reveal that the full-length NTD can be viewed as having at least two thermodynamically coupled regions, a functional region, which is indispensable for GR transcriptional activity, and a regulatory region, the length of which serves to regulate the stability of NTD and thus the activity of GR. These results suggest a new functional paradigm whereby steroid hormone receptors in particular and ID proteins in general can have multiple functionally distinct ID regions that interact and modulate the stability of important functional sites. PMID- 22669940 TI - Involvement of the up-regulated FoxO1 expression in follicular granulosa cell apoptosis induced by oxidative stress. AB - Follicular atresia is common in female mammalian ovaries, where most follicles undergo degeneration at any stage of growth and development. Oxidative stress gives rise to triggering granulosa cell apoptosis, which has been suggested as a major cause of follicular atresia. However, the underlying mechanism by which the oxidative stress induces follicular atresia remains unclear. FoxO transcription factors are known as critical mediators in the regulation of oxidative stress and apoptosis. In this study, the involvement of FoxO1 in oxidative stress-induced apoptosis of mouse follicular granulosa cells (MGCs) was investigated in vivo and in vitro. It was observed that increased apoptotic signals correlated with elevated expression of FoxO1 in MGCs when mice were treated with the oxidant. Correspondingly, the expressions of FoxO1 target genes, such as proapoptotic genes and antioxidative genes, were also up-regulated. In primary cultured MGCs, treatment with H(2)O(2) led to FoxO1 nuclear translocation. Further studies with overexpression and knockdown of FoxO1 demonstrated the critical role of FoxO1 in the induction of MGC apoptosis by oxidative stress. Finally, inactivation of FoxO1 by insulin treatment confirmed that FoxO1 induced by oxidative stress played a pivotal role in up-regulating the expression of downstream apoptosis related genes in MGCs. Our results suggest that up-regulation of FoxO1 by oxidative stress leads to apoptosis of granulosa cells, which eventually results in follicular atresia in mice. PMID- 22669941 TI - USP2a protein deubiquitinates and stabilizes the circadian protein CRY1 in response to inflammatory signals. AB - The mammalian circadian clock coordinates various physiological activities with environmental cues to achieve optimal adaptation. The clock manifests oscillations of key clock proteins, which are under dynamic control at multiple post-translational levels. As a major post-translational regulator, the ubiquitination-dependent proteasome degradation system is counterbalanced by a large group of deubiquitin proteases with distinct substrate preference. Until now, whether deubiquitination by ubiquitin-specific proteases can regulate the clock protein stability and circadian pathways remains largely unclear. The mammalian clock protein, cryptochrome 1 (CRY1), is degraded via the FBXL3 mediated ubiquitination pathway, suggesting that it is also likely to be targeted by the deubiquitination pathway. Here, we identified that USP2a, a circadian controlled deubiquitinating enzyme, interacts with CRY1 and enhances its protein stability via deubiquitination upon serum shock. Depletion of Usp2a by shRNA greatly enhances the ubiquitination of CRY1 and dampens the oscillation amplitude of the CRY1 protein during a circadian cycle. By stabilizing the CRY1 protein, USP2a represses the Per2 promoter activity as well as the endogenous Per2 gene expression. We also demonstrated that USP2a-dependent deubiquitination and stabilization of the CRY1 protein occur in the mouse liver. Interestingly, the pro-inflammatory cytokine, TNF-alpha, increases the CRY1 protein level and inhibits circadian gene expression in a USP2a-dependent fashion. Therefore, USP2a potentially mediates circadian disruption by suppressing the CRY1 degradation during inflammation. PMID- 22669942 TI - Multiple substitutions of methionine 129 in human prion protein reveal its importance in the amyloid fibrillation pathway. AB - The role of the polymorphism Met or Val in position 129 in the human prion protein is well documented regarding disease susceptibility and clinical manifestations. However, little is known about the molecular background to this phenomenon. We investigated herein the conformational stability, amyloid fibrillation kinetics, and seeding propensity of different 129 mutants, located in beta-strand 1 of PrP (Met(129) (WT), M129A, M129V, M129L, M129W, M129P, M129E, M129K, and M129C) in HuPrP(90-231). The mutations M129V, M129L, M129K, and M129C did not affect stability (midpoints of thermal denaturation, T(m) = 65-66 degrees C), whereas the mutants M129A and M129E and the largest side chain M129W were destabilized by 3-4 degrees C. The most destabilizing substitution was M129P, which lowered the T(m) by 7.2 degrees C. All mutants, except for M129C, formed amyloid-like fibrils within hours during fibril formation under near physiological conditions. Fibril-forming mutants showed a sigmoidal kinetic profile and showed shorter lag times during seeding with preformed amyloid fibrils implicating a nucleated polymerization reaction. In the spontaneous reactions, the lag time of fibril formation was rather uniform for the mutants M129A, M129V, and M129L resembling the wild type. When the substituted amino acid had a distinct feature discriminating it from the wild type, such as size (M129W), charge (M129E, M129K), or rotational constraint (M129P), the fibrillation was impeded. M129C did not form ThT/Congo red-positive fibrils, and non-reducing SDS-PAGE of M129C during fibrillation conditions at different time points revealed covalent dimer formation already 15 min after fibrillation reaction initiation. Position 129 appears to be a key site for dictating PrP receptiveness toward recruitment into the amyloid state. PMID- 22669943 TI - Dynamic imaging by fluorescence correlation spectroscopy identifies diverse populations of polyglutamine oligomers formed in vivo. AB - Protein misfolding and aggregation are exacerbated by aging and diseases of protein conformation including neurodegeneration, metabolic diseases, and cancer. In the cellular environment, aggregates can exist as discrete entities, or heterogeneous complexes of diverse solubility and conformational state. In this study, we have examined the in vivo dynamics of aggregation using imaging methods including fluorescence microscopy, fluorescence recovery after photobleaching (FRAP), and fluorescence correlation spectroscopy (FCS), to monitor the diverse biophysical states of expanded polyglutamine (polyQ) proteins expressed in Caenorhabditis elegans. We show that monomers, oligomers and aggregates co-exist at different concentrations in young and aged animals expressing different polyQ lengths. During aging, when aggregation and toxicity are exacerbated, FCS-based burst analysis and purified single molecule FCS detected a populational shift toward an increase in the frequency of brighter and larger oligomeric species. Regardless of age or polyQ-length, oligomers were maintained in a heterogeneous distribution that spans multiple orders of magnitude in brightness. We employed genetic suppressors that prevent polyQ aggregation and observed a reduction in visible immobile species with the persistence of heterogeneous oligomers, yet our analysis did not detect the appearance of any discrete oligomeric states associated with toxicity. These studies reveal that the reversible transition from monomers to immobile aggregates is not represented by discrete oligomeric states, but rather suggests that the process of aggregation involves a more complex pattern of molecular interactions of diverse intermediate species that can appear in vivo and contribute to aggregate formation and toxicity. PMID- 22669944 TI - Increased laforin and laforin binding to glycogen underlie Lafora body formation in malin-deficient Lafora disease. AB - The solubility of glycogen, essential to its metabolism, is a property of its shape, a sphere generated through extensive branching during synthesis. Lafora disease (LD) is a severe teenage-onset neurodegenerative epilepsy and results from multiorgan accumulations, termed Lafora bodies (LB), of abnormally structured aggregation-prone and digestion-resistant glycogen. LD is caused by loss-of-function mutations in the EPM2A or EPM2B gene, encoding the interacting laforin phosphatase and malin E3 ubiquitin ligase enzymes, respectively. The substrate and function of malin are unknown; an early counterintuitive observation in cell culture experiments that it targets laforin to proteasomal degradation was not pursued until now. The substrate and function of laforin have recently been elucidated. Laforin dephosphorylates glycogen during synthesis, without which phosphate ions interfere with and distort glycogen construction, leading to LB. We hypothesized that laforin in excess or not removed following its action on glycogen also interferes with glycogen formation. We show in malin deficient mice that the absence of malin results in massively increased laforin preceding the appearance of LB and that laforin gradually accumulates in glycogen, which corresponds to progressive LB generation. We show that increasing the amounts of laforin in cell culture causes LB formation and that this occurs only with glycogen binding-competent laforin. In summary, malin deficiency causes increased laforin, increased laforin binding to glycogen, and LB formation. Furthermore, increased levels of laforin, when it can bind glycogen, causes LB. We conclude that malin functions to regulate laforin and that malin deficiency at least in part causes LB and LD through increased laforin binding to glycogen. PMID- 22669945 TI - Synapses of amphids defective (SAD-A) kinase promotes glucose-stimulated insulin secretion through activation of p21-activated kinase (PAK1) in pancreatic beta Cells. AB - The p21-activated kinase-1 (PAK1) is implicated in regulation of insulin exocytosis as an effector of Rho GTPases. PAK1 is activated by the onset of glucose-stimulated insulin secretion (GSIS) through phosphorylation of Thr-423, a major activation site by Cdc42 and Rac1. However, the kinase(s) that phosphorylates PAK1 at Thr-423 in islet beta-cells remains elusive. The present studies identified SAD-A (synapses of amphids defective), a member of AMP activated protein kinase-related kinases exclusively expressed in brain and pancreas, as a key regulator of GSIS through activation of PAK1. We show that SAD A directly binds to PAK1 through its kinase domain. The interaction is mediated by the p21-binding domain (PBD) of PAK1 and requires both kinases in an active conformation. The binding leads to direct phosphorylation of PAK1 at Thr-423 by SAD-A, triggering the onset of GSIS from islet beta-cells. Consequently, ablation of PAK1 kinase activity or depletion of PAK1 expression completely abolishes the potentiating effect of SAD-A on GSIS. Consistent with its role in regulating GSIS, overexpression of SAD-A in MIN6 islet beta-cells significantly stimulated cytoskeletal remodeling, which is required for insulin exocytosis. Together, the present studies identified a critical role of SAD-A in the activation of PAK1 during the onset of insulin exocytosis. PMID- 22669946 TI - DNase I hypersensitive site II of the human growth hormone locus control region mediates an essential and distinct long-range enhancer function. AB - Locus control regions (LCRs) comprise sets of DNA elements capable of establishing autonomous chromatin domains that support robust and physiologically appropriate expression of target genes, often working over extensive distances. Human growth hormone (hGH-N) expression in the pituitary is under the regulation of a well characterized LCR containing four DNase I hypersensitive sites (HSs). The two pituitary-specific HS, HSI and HSII, are located 14.5 and 15.5 kb 5' to the hGH-N promoter. HSI is essential for activation of hGH-N during pituitary development and for sustaining robust activity in the adult. To determine whether the closely linked HSII has a role in hGH-N expression, it was deleted from a previously validated hGH/P1 transgene. Analysis of three independent hGH/P1(DeltaHSII) transgenic mouse lines revealed that this deletion had no adverse effect on the formation of HSI, yet resulted in a substantial loss (70%) in hGH-N mRNA expression. This loss of expression was accompanied by a corresponding reduction in recruitment of the pituitary-specific transcription factor Pit-1 to the hGH-N promoter and a selective decrease in promoter occupancy of the elongation-linked isoform of RNA polymerase II. Sufficiency of HSI and HSII in LCR activity was explored by establishing two additional sets of mouse transgenic lines in which DNA segments containing these HS were positioned within the lambda phage genome. In this "neutral" DNA context, HSII was required for the recruitment of HAT activity. These data establish HSII as a nonredundant component of the hGH LCR essential for establishment of robust levels of hGH-N gene expression. PMID- 22669947 TI - Intrinsic disorder in dynein intermediate chain modulates its interactions with NudE and dynactin. AB - The functional diversity of cytoplasmic dynein is in part attributed to multiple interactions between noncatalytic dynein subunits and an array of regulatory proteins. This study focuses on the interaction between the dynein intermediate chain subunit (IC) and a dynein regulator protein (NudE). We use isothermal titration calorimetry and NMR spectroscopy to map their interacting sections to their respective N-terminal domains, which are predicted to form dimeric coiled coils. Interestingly, the specific residues within IC that interact with NudE are a subset of the bi-segmental binding region reported for p150(Glued), a subunit of the dynein activator protein dynactin. Although the IC binding domains of both NudE and p150(Glued) form dimeric coiled-coils and bind IC at a common site, we observe distinct binding modes for each regulatory protein: 1) NudE binds region 1 of the bi-segmental binding footprint of p150(Glued), whereas p150(Glued) requires regions 1 and 2 to match the binding affinity of NudE with region 1 alone. 2) Compared with unbound IC, NudE-bound IC shows a slight increase in flexibility in region 2, in contrast to the increase in ordered structure observed for p150(Glued)-bound IC (Morgan, J. L., Song, Y., and Barbar, E. (2011) J. Biol. Chem. 286, 39349-39359). 3) Although NudE has a higher affinity for the common binding segment on IC, when all three proteins are in solution, IC preferentially binds p150(Glued). These results underscore the importance of a bi segmental binding region of IC and disorder in region 2 and flanking linkers in selecting which regulatory protein binds IC. PMID- 22669948 TI - The SH2B1 adaptor protein associates with a proximal region of the erythropoietin receptor. AB - Gene targeting experiments have shown that the cytokine erythropoietin (EPO), its cognate erythropoietin receptor (EPO-R), and associated Janus tyrosine kinase, JAK2, are all essential for erythropoiesis. Structural-functional and murine knock-in experiments have suggested that EPO-R Tyr-343 is important in EPO mediated mitogenesis. Although Stat5 binds to EPO-R phosphotyrosine 343, the initial Stat5-deficient mice did not have profound erythroid abnormalities suggesting that additional Src homology 2 (SH2) domain-containing effectors may bind to EPO-R Tyr-343 and couple to downstream signaling pathways. We have utilized cloning of ligand target (COLT) screening to demonstrate that EPO-R Tyr(P)-343 and Tyr(P)-401 bind to the SH2 domain-containing adaptor protein SH2B1beta. Immunoprecipitation and in vitro mixing experiments reveal that EPO-R binds to SH2B1 in an SH2 domain-dependent manner and that the sequence that confers SH2B1 binding to the EPO-R is pYXXL. Previous studies have shown that SH2B1 binds directly to JAK2, but we show that in hematopoietic cells, SH2B1beta preferentially associates with the EPO-R. SH2B1 is capable of constitutive association with EPO-R, which is necessary for its optimal SH2-dependent recruitment to EPO-R-Tyr(P)-343/Tyr(P)-401. We also demonstrate that SH2B1 is responsive to EPO stimulation and becomes phosphorylated, most likely on serines/threonines, in an EPO dose- and time-dependent manner. In the absence of SH2B1, we observe enhanced activation of signaling pathways downstream of the EPO R, indicating that SH2B1 is a negative regulator of EPO signaling. PMID- 22669949 TI - Socioeconomic status and hepatocellular carcinoma in the United States. AB - BACKGROUND: Hepatocellular carcinoma (HCC) has a poor prognosis and, unlike most cancers, HCC incidence and mortality rates are increasing in the United States. While risk is known to vary among different racial and ethnic groups, less is known about the variability of risk within these groups by neighborhood socioeconomic status (SES). METHODS: HCC cases diagnosed in the Surveillance, Epidemiology and End Results (SEER) 11 cancer registries between 1996 and 2007, and the population of the SEER 11 catchment areas was studied. Analyses were conducted to compare census tract area family poverty, educational attainment, and unemployment by race and ethnicity. A multiple linear regression model, weighted by the number of cases and the number of individuals in each census tract, with adjustment for registry, was used to calculate mean differences in area-level attributes between HCC cases and the population. RESULTS: HCC cases in most racial/ethnic groups had lower mean neighborhood-level measures of SES than their referent population. An exception was seen among Hispanics. Comparing white cases with cases of other racial groups and to Hispanics, white cases lived in neighborhoods with less family poverty, fewer high-school dropouts, and lower unemployment. Compared with white cases, Asian and Pacific Islander and Hispanic cases lived in neighborhoods with a higher percentage of foreign-born population. CONCLUSIONS: Low neighborhood-level SES and immigrant status may be associated with greater risk of HCC within specific racial and ethnic groups. IMPACT: These findings could help to focus control resources for HCC toward the most affected communities. PMID- 22669950 TI - Relationship between mean platelet volume and atherosclerosis in young patients with ST elevation myocardial infarction. AB - Increased mean platelet volume (MPV) is associated with poor clinical outcome in patients with acute coronary syndrome. We evaluated the predictive role of MPV in young patients with acute myocardial infarction (AMI). This study includes 373 patients who presented to our hospital with AMI (group 1: 134 young patients, males aged <45 years and females aged <55 years; group 2: 239 older patients) and 141 adults with normal coronary angiography as a control group (group 3). In group 1, the levels of MPV and hemoglobin were higher than that in groups 2 and 3. In group 1, blood urea nitrogen levels were lower than that in groups 2 and 3 and creatinine levels were lower than that in group 2. After multivariate analysis, MPV and age were independent predictors of AMI in young patients. PMID- 22669951 TI - ARISTOTLE expands the list of novel anticoagulants for thromboprophylaxis in atrial fibrillation. PMID- 22669953 TI - Complements do not lie. AB - A 74-year-old patient presented with constitutional symptoms and was found to have acute kidney injury. He was known to have a prosthetic aortic valve. He was febrile with splenomegaly and vasculitic lesions on both hands. Nephritic screen revealed strongly positive cytoplasmic-antineutrophil cytoplasmic antibodies (c ANCA). Differential diagnosis thus included a small vessel vasculitis or infective endocarditis. Transoesophageal echocardiography demonstrated no vegetations and serial blood cultures were negative. Immunosuppression for presumed granulomatosis with polyangiitis (Wegeners granulomatosis) was therefore instituted. The patient deteriorated, requiring multi-organ support. Renal biopsy showed a proliferative glomerulopathy and complements were low. Atypical screen for culture negative endocarditis revealed a strongly positive IgG-antibody titre against Bartonella henselae. Immunosuppression was discontinued and treatment for chronic Bartonellosis commenced. The patient made a remarkable recovery. His renal function quickly returned to normal, and ANCA titres and complements normalised. He was discharged home after completing a 6 week course of antibiotic therapy. PMID- 22669952 TI - Be aware of wood in the knee. AB - The authors report a case of a 7-year-old boy who sustained a penetrating injury of a splinter of wood to the knee. Arthroscopic examination, removal of visualised foreign material and washout did not alleviate the symptoms of pain and swelling in its entirety. Microbiology cultures also failed to determine the cause of the on-going symptoms. Five days later, the patient underwent a mini arthrotomy through a lateral incision, which demonstrated synovitis, and removal of the remaining embedded foreign body from the lateral condyle. Although the authors advocate arthroscopy as the surgeon's first choice for removal of a foreign body from the knee, a mini-arthrotomy should also be considered to facilitate superior visualisation and easier instrumentation to remove embedded foreign bodies. PMID- 22669954 TI - Periurethral pseudoabscess secondary to injection of an intraurethral bulking agent. PMID- 22669955 TI - An acute presentation of visceral artery aneurysm. AB - A 56-year-old patient presented with shock and severe abdominal pain. Initial blood tests, erect chest x-ray and focused ultrasound were not diagnostic. CT imaging demonstrated bleeding from a superior mesenteric artery aneurysm. Operative treatment with ligation of the bleeding point and packing of the abdomen successfully controlled the bleeding. He eventually made a full recovery. PMID- 22669956 TI - Rowell syndrome--case report with discussion of significance of diagnostic accuracy. AB - Rowell syndrome is a very controversial condition and though defining diagnosing criteria exist, many previously published cases lack one or more of these criteria. It represents the combination of cutaneous lupus erythematosus and erythema multiforme in one single individual. In order to discuss relevance of diagnostic and defining criteria the authors use a case seen in our outpatient service that was primarily diagnosed as Rowell syndrome. But due to lacking criteria, the authors rediagnosed this patient as an unusual variation of lupus erythematosus. PMID- 22669957 TI - Severe psoriatic acroosteolysis in the absence of psoriatic arthropathy. PMID- 22669958 TI - Group-A-streptococcal meningitis in a 7-year-old child--a rare pathogen in a non immune compromised patient. AB - A case is presented of meningitis in a 7-year-old female child caused by Group A streptococcus (GAS), a rare bacterial cause of meningitis, with a high rate of morbidity (46%) and mortality (10%). GAS is susceptible for empiric antibiotic therapy aimed at the most prevalent pathogens of meningitis. As GAS meningitis is typically associated with ear-nose-throat (ENT) infections, specific search for a reservoir is advised. Bacterial typification often demonstrates M-protein gene sequence type (EMM type) 1.0 associated with upper respiratory tract infections and also severe, invasive GAS infections. Follow-up investigation including neurologic developmental status and audiologic testing is necessary. Although GAS is a very uncommon cause of acute bacterial meningitis in children, high morbidity and mortality have been reported. Being associated with ENT infections, a search for a GAS reservoir is proposed. GASs are susceptible for common empiric antibiotic therapies in meningitis. Follow-up investigation is necessary. PMID- 22669960 TI - Paraneoplastic syndromes associated to Hodgkin's lymphoma. PMID- 22669959 TI - Transient binocular visual loss: a rare presentation of ventriculoperitoneal shunt malfunction. AB - The authors report the case of a 27-year-old male with ventriculoperitoneal shunt (VPS) for hydrocephalus presenting with episodic transient binocular visual loss (TBVL) and headache. Complete physical, bedside shunt examination and funduscopy were unremarkable. Laboratory investigation, shunt series and imaging studies failed to reveal any acute abnormalities. Interrogation of the shunt system identified a valve malfunction which was corrected with resultant symptomatic relief and the patient was discharged home in stable condition. VPS malfunction occurs secondary to infection or mechanical failure such as obstruction, tubing fracture, shunt migration and over drainage. Resultant raised intracranial pressure leads to symptoms of headache, nausea, vomiting and gait abnormalities. Visual defects including blindness has been occasionally reported from shunt malfunction. Rare complications include cerebrospinal fluid oedema, colonic perforation, paraparesis and parkinsonism. TBVL due to shunt malfunction remains an uncommon presentation and requires a high index of clinical suspicion while evaluating these patients. PMID- 22669961 TI - Pseudodementia due to intracranial tuberculomas: an unusual presentation. AB - Tuberculosis is highly prevalent in developing countries. Meningitis is by far the most frequent manifestation of tuberculosis in the central nervous system. Infrequently they may present as intracranial masses. Intracranial tuberculomas, either multiple or single, pose great diagnostic challenge because the appearance may resemble many other non-infectious and infectious conditions and particularly in patients without constitutional symptoms or evidence of tuberculosis elsewhere in the body. Here the author highlights an unusual presentation of intracranial tuberculomas in the form of pseudodementia where other constitutional symptoms were absent. PMID- 22669962 TI - Round cell epithelioid GIST (gastrointestinal stromal tumour) in an endoscopic biopsy is a diagnostic confounder. PMID- 22669963 TI - Cystic appearance: an uncommon feature of pulmonary metastasis of colorectal origin. PMID- 22669964 TI - Recurrent intramedullary epidermoid cyst of conus medullaris. AB - Spinal intramedullary epidermoid cyst is a rare condition. Recurrent epidermoid cyst in the spine cord is known to occur. The authors describe a case of recurrent conus medullaris epidermoid cyst in a 24-year-old female. She initially presented at 7 years of age with bladder disturbance in the form of diurnal enuresis and recurrent urinary tract infection. MRI lumbar spine revealed a 4 cm conus medullaris epidermoid cyst. Since the initial presentation, the cyst had recurred seven times in the same location and she underwent surgical intervention in the form of exploration and debulking. This benign condition, owing to its anatomical location, has posed a surgical and overall management challenge. This occurrence is better managed in a tertiary-care centre requiring multi disciplinary treatment approach. PMID- 22669965 TI - Running a risk? Sport supplement toxicity with ephedrine in an amateur marathon runner, with subsequent rhabdomyolysis. AB - A 36-year-old man presented to the emergency department acutely unwell after being found collapsed while running a halfmarathon. He presented with a reduced Glasgow coma score, was tachycardic, agitated, hypoxic and profusely sweating. He had taken a 'supplement' given to him prior to the race by a friend, as he was concerned about not finishing. This contained both caffeine and a large dose of ephedrine (60 mg in total). After initial resuscitation he was intubated, and was transferred to critical care. He subsequently developed rhabdomyolysis, requiring haemofiltration. PMID- 22669966 TI - Spontaneous corneal perforation post cataract surgery. AB - A 69-year-old female was referred for bilateral cataracts. Best-corrected visual acuity was 6/12 oculus dexter (OD) and 6/18 oculus sinister (OS). On examination, tear film breakup time was 8 s, signifying mild dry eyes; otherwise was unremarkable. The patient underwent uneventful left cataract surgery. At a 1 month postoperative examination vision was 6/9. The left cornea was dry with extensive punctuate epithelial erosions. There was no lagophthalmos. Lubricants were started to both eyes. The authors proceeded with right cataract surgery. Postoperative preservative free drops were given. She failed to attend an earlier than routine 2 week postoperative examination. Four weeks postoperatively, the vision was 2/60. She was incompliant with the lubricant drops. Biomicroscopic examination showed a sterile painless paracentral corneal perforation with iris plugging, Seidel's negative. She was started on steroid drops and lubricants. A lower lid punctual plug was inserted. The best corrected vision at 4 months was 6/18 OD and 6/6 OS. PMID- 22669967 TI - An unusual cause of lower gastrointestinal haemorrhage. AB - A previously unreported cause of lower gastrointestinal haemorrhage in a 63-year old female patient on clopidogrel for cardiac comorbidities is presented. Endoscopy suggested a small bowel or colonic aetiology but failed to accurately localise the source. The patient became haemodynamically unstable despite conservative management and temporary cessation of clopidogrel. CT angiography demonstrated a pseudoaneurysm arising from the superior rectal artery. Percutaneous embolisation using coils was performed to successfully occlude the pseudoaneurysm, prevent further haemorrhage and avoid emergency colonic resection. PMID- 22669968 TI - The theoretical and empirical basis for meditation as an intervention for PTSD. AB - In spite of the existence of good empirically supported treatments for posttraumatic stress disorder (PTSD), consumers and providers continue to ask for more options for managing this common and often chronic condition. Meditation based approaches are being widely implemented, but there is minimal research rigorously assessing their effectiveness. This article reviews meditation as an intervention for PTSD, considering three major types of meditative practices: mindfulness, mantra, and compassion meditation. The mechanisms by which these approaches may effectively reduce PTSD symptoms and improve quality of life are presented. Empirical evidence of the efficacy of meditation for PTSD is very limited but holds some promise. Additional evaluation of meditation-based treatment appears to be warranted. PMID- 22669969 TI - Postnatal aversive experience impairs sensitivity to natural rewards and increases susceptibility to negative events in adult life. AB - Evidence shows that maternal care and postnatal traumatic events can exert powerful effects on brain circuitry development but little is known about the impact of early postnatal experiences on processing of rewarding and aversive stimuli related to the medial prefrontal cortex (mpFC) function in adult life. In this study, the unstable maternal environment induced by repeated cross-fostering (RCF) impaired palatable food conditioned place preference and disrupted the natural preference for sweetened fluids in the saccharin preference test. By contrast, RCF increased sensitivity to conditioned place aversion (CPA) and enhanced immobility in the forced swimming test. Intracerebral microdialysis data showed that the RCF prevents mpFC dopamine (DA) outflow regardless of exposure to rewarding or aversive stimuli, whereas it induces a strong and sustained prefrontal norepinephrine (NE) release in response to different aversive experiences. Moreover, the selective mpFC NE depletion abolished CPA, thus indicating that prefrontal NE is required for motivational salience attribution to aversion-related stimuli. These findings demonstrate that an unstable maternal environment impairs the natural propensity to seek pleasurable sources of reward, enhances sensitivity to negative events in adult life, blunts prefrontal DA outflow, and modulates NE release in the reverse manner depending on the exposure to rewarding or aversive stimuli. PMID- 22669970 TI - Mental paper folding performance following penetrating traumatic brain injury in combat veterans: a lesion mapping study. AB - Mental paper folding is a complex measure of visuospatial ability involving a coordinated sequence of mental transformations and is often considered a measure of mental ability. The literature is inconclusive regarding the precise neural architecture that underlies performance. We combined the administration of the Armed Forces Qualification Test boxes subtest measuring mental paper folding ability, with a voxel-based lesion symptom mapping approach to identify brain regions associated with impaired mental paper folding ability. Using a large sample of subjects with penetrating traumatic brain injury and defined lesions studied over 2 time points, roughly 15 and 35 years post-injury, enabled us to answer the causal questions regarding mental paper folding impairment. Our results revealed that brain injury significantly exacerbates the decline of performance on mental paper folding tasks over time. Our study adds novel neuropsychological and neuroimaging support for parietal lobe involvement; specifically the right inferior parietal lobule (Broadmann's Area [BA] 40) and the left parahippocampal region (BAs 19, 36). Both areas were consistently associated with mental paper folding performance and demonstrate that the right parietal lobe and the left parahippocampal gyrus play an integral role in mental paper folding tasks. PMID- 22669971 TI - An investigation into adolescents' experience of cognitive behavioural therapy within a child and adolescent mental health service. AB - Cognitive Behavioural Therapy (CBT) is frequently referenced within NICE (National Institute for Clinical Excellence) guidance and is a recommended psychological therapy for a number of different mental health disorders for both adults and children. This is due to the current body of quantitative research around CBT demonstrating its efficacy for a range of mental health difficulties. However, CBT has not been as well addressed within the qualitative field and this gap in research is even more obvious when looking at CBT conducted with children and adolescents. This interpretative phenomenological study explored adolescents' experiences of a course of CBT within a Child and Adolescent Mental Health Service (CAMHS) in a one-to-one format. Three female adolescents who had completed an agreed contract of therapy with the CBT service took part in semi structured interviews. Four superordinate themes emerged from analysis and highlighted components within CBT that were important to the sample. These were engagement, the therapeutic relationship, the impact of CBT on change and the manner in which CBT was delivered. The findings are discussed with relevance to current policy and pertinent literature as well as implications for service delivery and future research. PMID- 22669972 TI - NF-kappaB directly regulates Fas transcription to modulate Fas-mediated apoptosis and tumor suppression. AB - Fas is a member of the death receptor family. Stimulation of Fas leads to induction of apoptotic signals, such as caspase 8 activation, as well as "non apoptotic" cellular responses, notably NF-kappaB activation. Convincing experimental data have identified NF-kappaB as a critical promoter of cancer development, creating a solid rationale for the development of antitumor therapy that suppresses NF-kappaB activity. On the other hand, compelling data have also shown that NF-kappaB activity enhances tumor cell sensitivity to apoptosis and senescence. Furthermore, although stimulation of Fas activates NF-kappaB, the function of NF-kappaB in the Fas-mediated apoptosis pathway remains largely undefined. In this study, we observed that deficiency of either Fas or FasL resulted in significantly increased incidence of 3-methylcholanthrene-induced spontaneous sarcoma development in mice. Furthermore, Fas-deficient mice also exhibited significantly greater incidence of azoxymethane and dextran sodium sulfate-induced colon carcinoma. In addition, human colorectal cancer patients with high Fas protein in their tumor cells had a longer time before recurrence occurred. Engagement of Fas with FasL triggered NF-kappaB activation. Interestingly, canonical NF-kappaB was found to directly bind to the FAS promoter. Blocking canonical NF-kappaB activation diminished Fas expression, whereas blocking alternate NF-kappaB increased Fas expression in human carcinoma cells. Moreover, although canonical NF-kappaB protected mouse embryo fibroblast (MEF) cells from TNFalpha-induced apoptosis, knocking out p65 diminished Fas expression in MEF cells, resulting in inhibition of FasL-induced caspase 8 activation and apoptosis. In contrast, knocking out p52 increased Fas expression in MEF cells. Our observations suggest that canonical NF-kappaB is a Fas transcription activator and alternate NF-kappaB is a Fas transcription repressor, and Fas functions as a suppressor of spontaneous sarcoma and colon carcinoma. PMID- 22669973 TI - Fission yeast Dma1 requires RING domain dimerization for its ubiquitin ligase activity and mitotic checkpoint function. AB - In fission yeast (Schizosaccharomyces pombe), the E3 ubiquitin ligase Dma1 delays cytokinesis if chromosomes are not properly attached to the mitotic spindle. Dma1 contains a C-terminal RING domain, and we have found that the Dma1 RING domain forms a stable homodimer. Although the RING domain is required for dimerization, residues in the C-terminal tail are also required to help form or stabilize the dimeric structure because mutation of specific residues in this region disrupts Dma1 dimerization. Further analyses showed that Dma1 dimerization is required for proper localization at spindle pole bodies and the cell division site, E3 ligase activity, and mitotic checkpoint function. Thus, Dma1 forms an obligate dimer via its RING domain, which is essential for efficient transfer of ubiquitin to its substrate(s). This study further supports the mechanistic paradigm that many RING E3 ligases function as RING dimers. PMID- 22669974 TI - Oligomerization of heme o synthase in cytochrome oxidase biogenesis is mediated by cytochrome oxidase assembly factor Coa2. AB - The synthesis of the heme a cofactor used in cytochrome c oxidase (CcO) is dependent on the sequential action of heme o synthase (Cox10) and heme a synthase (Cox15). The active state of Cox10 appears to be a homo-oligomeric complex, and formation of this complex is dependent on the newly synthesized CcO subunit Cox1 and the presence of an early Cox1 assembly intermediate. Cox10 multimerization is triggered by progression of Cox1 from the early assembly intermediate to downstream intermediates. The CcO assembly factor Coa2 appears important in coupling the presence of newly synthesized Cox1 to Cox10 oligomerization. Cells lacking Coa2 are impaired in Cox10 complex formation as well as the formation of a high mass Cox15 complex. Increasing Cox1 synthesis in coa2Delta cells restores respiratory function if Cox10 protein levels are elevated. The C-terminal segment of Cox1 is important in triggering Cox10 oligomerization. Expression of the C terminal 54 residues of Cox1 appended to a heterologous matrix protein leads to efficient Cox10 complex formation in coa2Delta cells, but it fails to induce Cox15 complex formation. The state of Cox10 was evaluated in mutants, which predispose human patients to CcO deficiency and the neurological disorder Leigh syndrome. The presence of the D336V mutation in the yeast Cox10 backbone results in a catalytically inactive enzyme that is fully competent to oligomerize. Thus, Cox10 oligomerization and catalytic activation are separate processes and can be uncoupled. PMID- 22669975 TI - Pellino 2 is critical for Toll-like receptor/interleukin-1 receptor (TLR/IL-1R) mediated post-transcriptional control. AB - Interleukin 1 receptor-associated kinase 1(IRAK1), a key molecule in TLR/IL-1R mediated signaling, is phosphorylated, ubiquitinated, and degraded upon ligand stimulation. We and others have recently identified Pellino proteins as novel RING E3 ubiquitin ligases involved in IRAK1 polyubiquitination and degradation. However, it remains unclear how each Pellino member distinctly regulates TLR/IL 1R signaling by modulating IRAK1 ubiquitination. In this study we examined the role of Pellino 2 in IL-1- and LPS-mediated signaling and gene expression by knocking down Pellino 2 in human 293-IL-1R cells and primary bone marrow macrophages. Pellino 2 (but not Pellino 1) knockdown abolished IL-1- and LPS induced Lys-63-linked IRAK1 ubiquitination with reduced Lys-48-linked IRAK1 ubiquitination. Furthermore, Pellino 2 is required for TAK1-dependent NFkappaB activation. However, because of the retained TAK1-independent NFkappaB activation, the levels of IL-1- and LPS-induced NFkappaB activation were not substantially affected in Pellino 2 knockdown 293-IL-1R cells and primary macrophages, respectively. On the other hand, Pellino 2 knockdown reduced the IL 1- and LPS-induced inflammatory gene expression at late time points, which was accompanied by increased decay rates of the mRNAs of the inflammatory genes. Importantly, IL-1- and LPS-mediated JNK and ERK activation were substantially attenuated in Pellino 2 knock-down cells, implicating MAPK activation in TLR/IL 1R-induced mRNA stabilization. Taken together, this study demonstrated that Pellino 2 plays a critical role for TLR/IL-1R-mediated post-transcriptional control. PMID- 22669976 TI - Human axonal survival of motor neuron (a-SMN) protein stimulates axon growth, cell motility, C-C motif ligand 2 (CCL2), and insulin-like growth factor-1 (IGF1) production. AB - Spinal muscular atrophy is a fatal genetic disease of motoneurons due to loss of full-length survival of motor neuron protein, the main product of the disease gene SMN1. Axonal SMN (a-SMN) is an alternatively spliced isoform of SMN1, generated by retention of intron 3. To study a-SMN function, we generated cellular clones for the expression of the protein in mouse motoneuron-like NSC34 cells. The model was instrumental in providing evidence that a-SMN decreases cell growth and plays an important role in the processes of axon growth and cellular motility. In our conditions, low levels of a-SMN expression were sufficient to trigger the observed biological effects, which were not modified by further increasing the amounts of the expressed protein. Differential transcriptome analysis led to the identification of novel a-SMN-regulated factors, i.e. the transcripts coding for the two chemokines, C-C motif ligands 2 and 7 (CCL2 and CCL7), as well as the neuronal and myotrophic factor, insulin-like growth factor 1 (IGF1). a-SMN-dependent induction of CCL2 and IGF1 mRNAs resulted in increased intracellular levels and secretion of the respective protein products. Induction of CCL2 contributes to the a-SMN effects, mediating part of the action on axon growth and random cell motility, as indicated by chemokine knockdown and re addition studies. Our results shed new light on a-SMN function and the underlying molecular mechanisms. The data provide a rational framework to understand the role of a-SMN deficiency in the etiopathogenesis of spinal muscular atrophy. PMID- 22669978 TI - Ring-enhancing central nervous system lesions. PMID- 22669977 TI - Opticin exerts its anti-angiogenic activity by regulating extracellular matrix adhesiveness. AB - Opticin is an extracellular matrix glycoprotein that we identified associated with the collagen network of the vitreous humor of the eye. Recently, we discovered that opticin possesses anti-angiogenic activity using a murine oxygen induced retinopathy model: here, we investigate the underlying mechanism. Using an ex vivo chick chorioallantoic membrane assay, we show that opticin inhibits angiogenesis when stimulated by a range of growth factors. We show that it suppresses capillary morphogenesis, inhibits endothelial invasion, and promotes capillary network regression in three-dimensional matrices of collagen and Matrigel(TM). We then show that opticin binds to collagen and thereby competitively inhibits endothelial cell interactions with collagen via alpha(1)beta(1) and alpha(2)beta(1) integrins, thereby preventing the strong adhesion that is required for proangiogenic signaling via these integrins. PMID- 22669979 TI - Is there a role for expired medications in developing countries? PMID- 22669980 TI - Maternal experience of interactions with providers among mothers with milk supply concern. AB - BACKGROUND: Milk supply concern is the most common reason given by mothers for discontinuing breastfeeding. OBJECTIVES. To describe maternal experiences of interactions with health care providers related to milk supply. PATIENTS AND METHODS: Ten focus groups (N = 56 participants) were conducted among mothers who had had milk supply concern in the first month after birth. Group sessions were audio-recorded, transcribed, coded, and analyzed to identify themes. Results. Interactions regarding milk supply concern evoked strong emotions, including gratitude, guilt, disappointment, and fear, and measurement of infant weight was frequently reported as a trigger for these emotions. Some mothers reported that experiencing "pressure" and "guilt" when providers emphasized exclusive breastfeeding led to suboptimal breastfeeding choices. CONCLUSIONS: Interactions with providers about milk supply concern evoke strong emotions among mothers. Providers should be aware that how they communicate routine advice regarding infant weight and formula may have unintended consequences, including discontinuation of breastfeeding. PMID- 22669981 TI - Progressive familial intrahepatic cholestasis type 3: overlapping presentation with Wilson disease. PMID- 22669982 TI - Small-animal PET of steroid hormone receptors predicts tumor response to endocrine therapy using a preclinical model of breast cancer. AB - Estrogen receptor-alpha (ERalpha) and progesterone receptor (PR) are expressed in most human breast cancers and are important predictive factors for directing therapy. Because of de novo and acquired resistance to endocrine therapy, there remains a need to identify which ERalpha-positive (ERalpha(+))/PR-positive (PR(+)) tumors are most likely to respond. The purpose of this study was to use estrogen- and progestin-based radiopharmaceuticals to image ERalpha and PR in mouse mammary tumors at baseline and after hormonal therapy and to determine whether changes in these imaging biomarkers can serve as an early predictive indicator of therapeutic response. METHODS: Mammary adenocarcinomas that spontaneously develop in aged female mice deficient in signal transducer and activator of transcription-1 (STAT1) were used. Imaging of ERalpha and PR in primary tumor-bearing mice and mice implanted with mammary cell lines (SSM1, SSM2, and SSM3) derived from primary STAT1-deficient (STAT1(-/-)) tumors was performed. Hormonal treatments consisted of estradiol, an ER agonist; letrozole, an aromatase inhibitor; and fulvestrant, a pure ER antagonist. Small-animal PET/CT was performed using (18)F-fluoroestradiol ((18)F-FES) for ER, (18)F-fluoro furanyl norprogesterone ((18)F-FFNP) for PR, and (18)F-FDG for glucose uptake. Tracer uptake in the tumor was quantified and compared with receptor concentration determined by in vitro assays of resected tumors. RESULTS: Primary STAT1(-/-) mammary tumors and implanted SSM2 and SSM3 tumors showed high (18)F FES and (18)F-FFNP uptake and were confirmed to be ERalpha(+)/PR(+). Classic estrogen-induced regulation of the progesterone receptor gene was demonstrated by increased (18)F-FFNP uptake of estradiol-treated SSM3 tumors. Treatment with fulvestrant decreased (18)F-FFNP, (18)F-FES, and (18)F-FDG uptake and inhibited growth of SSM3 tumors but decreased only (18)F-FES uptake in SSM2 tumors, with no effect on growth, despite both tumors being ERalpha(+)/PR(+). Decreased (18)F FFNP uptake by SSM3 tumors occurred early after initiation of treatment, before measurable tumor growth inhibition. CONCLUSION: Using small-animal PET, a profile was identified that distinguished fulvestrant-sensitive from fulvestrant resistant ERalpha(+)/PR(+) tumors before changes in tumor size. This work demonstrates that imaging baseline tumoral (18)F-FES uptake and initial changes in (18)F-FFNP uptake in a noninvasive manner is a potentially useful strategy to identify responders and nonresponders to endocrine therapy at an early stage. PMID- 22669984 TI - Scar sarcoidosis with bone marrow involvement and associated musculoskeletal symptoms. AB - Sarcoidosis affects the lungs most commonly and can present with cutaneous lesions. It can also involve the bone marrow in rare instances, often presenting with non-specific symptoms such as fever and malaise, with occasional haematological abnormalities. The authors present the case of a 41-year-old caucasian female who was diagnosed with scar sarcoidosis, but who also reported fatigue, night sweats and polyarthralgia. No haematological abnormalities or lung involvement were detected. A magnetic resonance scan of the spine, performed due to disc prolapses, demonstrated areas of bone oedema and stress response that were reported as a possible sarcoid infiltration of the bone marrow. An improvement occurred after 8 weeks, despite conservative treatment. Bone marrow involvement in sarcoidosis is rarely reported, and was an accidental finding here. Due to the non-specific presentation, cases such as this are potentially underdiagnosed and should be considered in patients with systemic symptoms, regardless of their haematological status. PMID- 22669985 TI - The tale of two tumours: an undiagnosed case of papillary thyroid carcinoma. AB - Pituitary metastasis is an infrequent clinical problem occurring in 1%-5% of various autopsy series. Differentiated thyroid carcinoma as the primary malignancy was reported in only 2.1% of the cases. A 53-year-old Filipina presented with 7 months history of progressive loss of vision and headaches. She underwent thyroidectomy 2 years prior to admission for an enlarging neck mass. After then, she was lost to follow-up. Physical examination revealed visual field loss, galactorrhea and a 3*4 cm firm suprasternal mass. Imaging showed a 4.5*5*5 cm mass in the sphenoid and ethmoid sinuses with extension into the sella and suprasellar regions. Biopsy of the mass was consistent with papillary thyroid carcinoma, metastatic. For that, she underwent completion thyroidectomy, followed by surgical debulking of the sellar mass. Postoperatively, there was minimal improvement in vision and 13 months after, she is still on constant follow-up in our clinic, and is due for radioiodine therapy. PMID- 22669986 TI - Life-threatening hyponatraemia and intramuscular olanzapine: the world's longest therapeutic trial. AB - This case report provides a different perspective on the management of a patient with a psychotic illness. The detained patient, a man aged 50, had specific delusional beliefs about toxins affecting his kidneys, such that he needed to drink water to 'detoxify' himself. This resulted in him developing life threatening hyponatraemia. It became clear that he was very resistant to taking oral medication and was reluctant to engage with any psychological treatment. A novel approach was considered, involving the 'off licence' use of short acting intramuscular olanzapine for the successful treatment of the psychotic illness. The case demonstrates the safe use of intramuscular olanzapine for 155 days, which is the longest reported case for the use of intramuscular olanzapine for the treatment of a psychotic illness. The individual was later discharged on oral olanzapine. PMID- 22669987 TI - CADASIL: how to avoid the unavoidable? AB - All three siblings (one female/two males) of a family presented successively with cerebrovascular events at the ages of 55, 63 and 65. The first one manifested extensive left subcortical haemorrhage and both the second and third patient, showed left lacunar ischemic stroke. Their mother had died from vascular dementia at the age of 60 after several subcortical ischaemic strokes. Their maternal grandfather had died in his fifties from haemorrhagic stroke. All of them showed extensive white matter involvement. The genetic study revealed a mutation in exon 11 of the Notch3 gene in two family members. They were diagnosed with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Although CADASIL is a well-established disease, little is known about this disorder. The fact that all three siblings presented with CADASIL successively may appear disheartening, further studies are needed in order to control the clinical course of this devastating and unavoidable disorder. PMID- 22669988 TI - 'A lipaemic mystery': a patient with hypertriglyceridaemic pancreatitis and cerebral infarction. AB - Hypertriglyceridaemia (HTG) causes up to 10% of all cases of acute pancreatitis (AP). It is the third most common cause after gallstones and alcohol. Despite this frequency, there are no clear guidelines for its specific management, mainly due to the paucity of evidence. The authors present a case and discussion of hypertriglyceridaemic pancreatitis (HTGP) complicated by an acute cerebral infarct. The patient's subsequent death secondary to cerebral infarction opens the discussion as to whether HTG should be more urgently treated. PMID- 22669989 TI - Management of traumatic intrusive luxation of incisors in a patient with Down's syndrome. AB - Special needs individuals are children or adults who are prevented by a physical or mental condition from full participation in the normal range of activities of their age groups. They usually exhibit high treatment needs because of an increased prevalence and severity of trauma. This paper presents a case report and review of treatment strategy of repositioning, splinting of permanent incisors in a 13-year-old boy with Down's syndrome sustaining trauma led to intrusive luxation of maxillary incisors. The intruded incisors were immediately repositioned and splinted with composite within hours. PMID- 22669990 TI - Symptomatic ring-shaped lateral meniscus. MRI findings. AB - Ring-shaped lateral meniscus is a rare clinical entity that is usually asymptomatic. Moreover, diagnosis is always based on arthroscopic exploration of lateral meniscus. MRI has not been proven useful so far because the inner portion of the ring-shaped lateral meniscus is usually misinterpreted as a bucket-handle tear. The authors report a case of a 16-year-old girl with ring-shaped lateral meniscus in combination with a meniscal cyst. MRI demonstrated a cyst arising from lateral meniscus and meniscal tissue into the inner portion of the lateral compartment mimicking displaced meniscal fragment. Bucket-handle tears have not been reported to cause or accompany meniscal cysts. As a result the diagnosis of a ring-shaped lateral meniscus along with meniscal cyst was assumed based on MRI and confirmed during arthroscopy. The patient was treated with arthroscopic partial lateral meniscectomy and intra-articular cyst debridement. PMID- 22669991 TI - Smells like a heart attack, but is it? AB - Methaemoglobinaemia is rare. Acute myocardial infarction (AMI) is common. The authors present a unique case of methaemaglobinaemia masquerading as an AMI. A middle-aged male was urgently referred to a tertiary cardiac centre for primary percutaneous coronary intervention with acute chest pain, cyanosis and tachycardia. However, on arrival, his ECG was felt to be within normal limits. Similarly unremarkable, were his echocardiogram and routine blood tests. Arterial blood gas analysis revealed a methaemaglobinaemia of 28.5% which normalised spontaneously. This was thought to be secondary to the use of smelling salts, inhaled earlier that day in the gymnasium. This is the first reported case of smelling salts inducing methaemaglobinaemia and of methaemaglobinaemia mimicking an AMI. PMID- 22669992 TI - Ifosfamide induced Fanconi syndrome. AB - Ifosfamide (IFA) is a powerful chemotherapeutic drug that is active against a variety of paediatric malignancies. However, renal toxicities such as haemorrhagic cystitis and Fanconi syndrome are major hazards that hinder its use in clinical practice. The authors present a case of a patient treated for Wilms' tumour with IFA who developed rickets with Fanconi syndrome. Patients undergoing IFA treatment must be carefully monitored for the development of iatrogenic complications. Recent studies have improved our understanding of the underlying pathomechanism of IFA induced Fanconi syndrome, and selective renal protection against during chemotherapy with IFA may be possible soon. PMID- 22669993 TI - Radiolucent wooden foreign body masquerading as a depressed skull fracture. AB - The following case describes a head injury in an older male patient in which a large wooden foreign body, forming a subcutaneous tract in the scalp, was mistaken for a depressed skull fracture on initial clinical assessment. This foreign body was not visualised on CT brain imaging until specialised views were used retrospectively, after surgical exploration of the scalp laceration. Appropriate radiological techniques for the detection of radiolucent foreign bodies are discussed. PMID- 22669994 TI - Fast atrial fibrillation and caecal volvulus--a case report and evidence based management. AB - An 81-year-old Caucasian lady with permanent atrial fibrillation (AF) was admitted with palpitations and fast AF. She took bisoprolol and warfarin with subtherapeutic international normalised ratio. Rate control of AF was successful. Around 36 h later, she developed abdominal pain and vomiting. A caecal volvulus was diagnosed on CT. She underwent emergency laparotomy. Intraoperatively, an obstructing tumour was found in the colonic hepatic flexure. It was deemed inoperable. The caecal volvulus was decompressed and an ileo-transverse colon bypass was performed. She made a good recovery and her fast AF settled postoperatively. She was seen by the oncology team and was discharged with palliative care support with no further exacerbation of AF. PMID- 22669995 TI - Acute cardiogenic pulmonary oedema with multiorgan dysfunction--still to learn more about nitrobenzene poisoning. AB - Nitrobenzene is a nitrite compound often used in polishes or solvents. Its toxic effects are due to its ability to induce methaemoglobinaemia. The clinical presentation of this poisoning varies according to the concentration of methaemoglobin level in blood. The importance of early identification of the compound on the basis of clinical suspicion corroborative with methaemoglobin level with timely intervention is required to prevent fatal outcome. It is also important to take care of the secondary cycling of nitrobenzene from body stores to prevent secondary recurrence of symptoms in patients after heavy exposure. Here author reports a rare case of accidental poisoning with nitrobenzene presented with respiratory distress and cyanosis. On investigation, he was diagnosed to have cardiogenic pulmonary oedema and multiorgan dysfunction. The urgent institution of methylene blue as specific antidote along with haemodynamic and ventilatory support was proved crucial for life saving of the patient. PMID- 22669996 TI - Uterine myxoid leiomyosarcoma with an underlying haematological disorder--case report and review of literature. AB - Uterine myxoid leiomyosarcoma is an exceptionally unusual variant of leiomyosarcoma with only 34 cases having been reported in the literature. The authors describe a case of myxoid leiomyosaroma with an underlying haematological profile that has not been described previously. A 38-year-old Caucasian woman with a known uterine fibroid discovered during pregnancy presented to the emergency department with heavy per vaginal bleeding. On examination, she had a large abdominal mass. She had a haemoglobin level of 5.2, platelets of 16 and a low white cell count. She received multiple blood and platelet transfusions, despite which her haemoglobin and platelet count levels remained low. She underwent two bone marrow biopsies, which were inconclusive. She underwent laparotomy for abdominal hysterectomy, bilateral salphingo-oohphorectomy, omentectomy and appendicectomy. Histological examination showed uterine myxoid leiomyosarcoma (International Federation of Gynaecology and Obstetrics stage IIIA). Her haematological profile improved significantly following surgical resection of the tumour, reappearing with the recurrence of the disease. The authors hence, consider that pancytopaenia in this patient was a manifestation of paraneoplastic syndrome. PMID- 22669997 TI - Lupus mastitis: a mimicker of breast carcinoma. AB - The authors present a case of lupus mastitis which was initially diagnosed following an incisional biopsy of a breast lump, with similar pathology found 2 years later after an ultrasound guided biopsy of the same lump. The woman had been diagnosed 7 years before with systemic lupus erythematosus. The radiological and pathological features are presented in this report with discussion of similar cases in the literature. PMID- 22669998 TI - Bronchogenic adenocarcinoma presenting as a synchronous solitary lytic skull lesion with ischaemic stroke--case report and literature review. AB - The authors describe a rare case of metastatic bronchogenic adenocarcinoma in a 55-year-old man presenting with concomittant solitary lytic skull lesion and ischaemic stroke. Metastatic bronchogenic carcinoma is known to present as lytic skull lesions. Primary brain tumours are also known to cause ischaemic brain injury. An underlying stroke risk may be exagerated by cranial tumour surgery. Patients with brain tumours are well known to be predisposed to an increased risk of developing thromboembolic disease. It is unusual to see metastatic bronchogenic adenocarcinoma presenting as ischaemic stroke with a background of concomittant cerebral metastasis. The aetio-pathogenesis of this rare occurrence is discussed with a review of literature. PMID- 22669999 TI - Schizophrenia and Parkinson's disease: challenges in management. AB - A 57-year-old gentleman was admitted for relapse of psychotic symptoms. He had prior diagnosis of schizophrenia and Parkinson's disease. His psychotropic medications were adjusted but his neurological symptoms worsened, mainly dysphagia. His speech and mobility also posed significant problem. Neurology department was contacted for joint management. In the event of resolution of psychotic symptoms, he was transferred to the neurology department for further management. His medication for Parkinson's disease was reviewed; a percutaneous endoscopic gastrostomy tube was inserted in stomach for feeding as dysphagia did not improve. He was transferred back to psychiatry unit for further adjustment in psychotropic medication in order to see a possible improvement in dysphagia. Minor adjustment was done in this regard in view of his mental health stability. Change of medication was not possible for the possible side effects and patient's compliance issue. He was discharged with adequate plans; follow-up arrangement and suggestions for further management. PMID- 22670000 TI - Evil lurks in the heart of man: cardiac paraganglioma presenting as recurrent dyspnoea and chronic cough. AB - A man in his 60s presents with chronic dyspnoea and cough for 3 years. EKG and nuclear stress test were not diagnostic. An echocardiogram revealed moderate pericardial effusion. His symptoms improved with ibuprofen temporarily and a repeat echocardiogram showed resolution of the effusion. However, when his symptoms recurred, re-imaging showed a large intracardiac tumour causing right ventricular outflow obstruction. Subsequent histological examination revealed metastatic paraganglioma. He was found to carry a germline mutation in the SDHB gene which is associated with higher malignant risk. Knowledge of his underlying mutation allowed the patient and his family to receive appropriate gene-specific counselling and surveillance. PMID- 22670001 TI - Diagnostic uncertainty around seizures in advanced malignancy. AB - A 70-year-old lady with a resected Dukes B colon cancer, receiving adjuvant capecitabine and bevacizumab chemotherapy was admitted with Hickman line sepsis. During her admission, she developed seizures and periods of unresponsiveness and was suspected to have brain metastases. She was started on high dose steroids and sodium valproate and appeared to respond to this treatment. However an MRI scan revealed that she did not have brain metastases but a rare neurological condition called reversible posterior leukoencephalopathy syndrome, which can be fatal if not treated but has a good prognosis if the cause is identified and treated. PMID- 22670002 TI - Staphylococcal scalded skin syndrome in a preterm newborn presenting within first 24 h of life. AB - A preterm neonate was noted to have diffuse blanching erythema around the mouth followed by appearance of bullous lesions on the upper back, lower neck and right scapular areas at 23 h of life. The bullae subsequently ruptured leaving an extremely tender, erythematous, denuded area of the skin, which extended over next few hours to involve most of the upper back and right shoulder regions. Nikolsky sign was positive. Clinical diagnosis of staphylococcal scalded skin syndrome was made. The throat, blood, urine and cerebrospinal fluid cultures did not yield any growth, but wound culture was positive for Staphylococcus aureus. Treatment included administration of intravenous fluids and vancomycin for 10 days. The wound area was covered with vaseline and sterile gauge dressings. On day 5 of life, epithelialisation began and was complete on the seventh day of life. She was discharged home with intact skin, without scars, on day 12 of life. PMID- 22670003 TI - Recurrent haemoptysis, left-sided chest pain and an evolving left lower lobe cavity in a 50-year old smoker with prior high ethanol intake. AB - The authors describe a case of pancreatico-pleural fistula that presented as recurrent pyogenic chest disease in a patient with underlying ethanol related pancreatic disease. The diagnosis was suspected, given the context of non resolving chest sepsis despite repeated antibiotics in a patient with known pancreatic disease. Although not revealed by initial tests the diagnosis was confirmed by repeating imaging investigations. The fistula was repaired surgically with consequent resolution of chest disease without need for extensive thoracic surgery. PMID- 22670004 TI - Sweet's syndrome after adalimumab therapy for refractory relapsing polychondritis. AB - Relapsing polychondritis and Sweet's syndrome are rare systemic inflammatory conditions. The authors present a patient who developed Sweet's syndrome 1 week after adalimumab therapy for refractory relapsing polychondritis. Coexistent relapsing polychondritis and Sweet's syndrome is rare, however, is likely to represent a true disease association and signifies a high risk of myelodysplasia. Antitumour necrosis factor alpha (TNFalpha) therapy is a treatment option in both relapsing polychondritis and Sweet's syndrome, and switching anti-TNFalpha agents may be feasible in the event of adverse reaction. PMID- 22670005 TI - Two different management modalities in a two sibling case report of Adams Oliver syndrome. AB - The authors report two-sibling case of Adams Oliver syndrome. One was managed with early surgical intervention after a period of failed conservative management and the other conservatively managed until reconstruction and surgical correction of alopecia. The goal of treatment is to achieve a complete closure of the defect without encountering any fatal complications such as haemorrhage and infection or causing any long-term neurological morbidity. Various papers have been published related to ACC, yet there is no consensus on the therapeutic approach. The management decision hinges upon balancing the risks of complications including spontaneous sagittal sinus haemorrhage and the risk of surgical intervention. Both treatment modalities proved successful in these cases. PMID- 22670006 TI - Lymphadenopathy and hepatosplenomegaly in a patient with acute myelogenous leukaemia. PMID- 22670007 TI - Early radiological findings on CT in a patient with enteropathy-associated T cell lymphoma. PMID- 22670008 TI - Mediastinal mass-a rare presentation of desmoplastic small round cell tumour. AB - Primary mediastinal desmoplastic small round cell cancer is an uncommon tumour usually located in the abdomen and pelvis. Here the authors report an extremely rare case of a young male with a primary desmoplastic small round cell tumour in the anterior and middle mediastinum. The patient had non-specific complaints but an abnormal shadow was seen in a routine chest x-ray. He was diagnosed as having mediastinal mass with few lung parenchymal deposits on CT. Mediastinoscopy and guided biopsy revealed desmoplastic small round cell tumour. Desmoplastic small round cell tumour is a rare and aggressive tumour which rarely involves the mediastinum as a primary site. The nature of the lesion and its prognosis were explained to the patient. He was offered chemotherapy and radiotherapy for the tumour management. He refused treatment and left against medical advice. PMID- 22670009 TI - Isolated penile lymphoedema: surgical management. PMID- 22670010 TI - Clinical aspects of congenital syphilis with Hutchinson's triad. AB - Congenital syphilis is an infectious disease caused by Treponema pallidum transmitted by infected mother to her baby during pregnancy. Late congenital syphilis is recognised with 2 or more years after birth. One of the main aspects is observed with the triad of Hutchinson, characterised by the presence of interstitial keratitis, eighth nerve deafness and Hutchinson's teeth. This manuscript reports a case of late congenital syphilis presenting with Hutchinson's triad at an age of 7 years. These clinical features are related to syphilis present during pregnancy and at birth, however they commonly become apparent after 5-years of age. PMID- 22670011 TI - The dark side of SAPHO syndrome. AB - SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis and osteitis) is a relatively rare entity. The therapeutic approach of patients with SAPHO syndrome has included multiple drugs with varying success and incoherence responses. The therapy is still empirical today. SAPHO syndrome is commonly treated with non steroidal anti-inflammatory drugs, bisphophonates and non-biologic disease modifying antirheumatic drugs. Recent reports showed successful treatment with tumour necrosis factor alpha (TNF alpha) antagonists, but there is still a dark side of SAPHO syndrome including a subgroup of patient's refractory to all the treatments that have been empirically experienced. A clinical report of a patient with SAPHO syndrome with 12 years of evolution is described. All the therapeutic approaches, including anti TNF alpha therapy, have not prevented the clinical and radiographic progression of the disease. Given that the disease affects mostly younger patients, new therapeutic strategies are necessary in order to avoid potentially irreversible joint and bone lesions. PMID- 22670012 TI - Longitudinal evaluation of MPIO-labeled stem cell biodistribution in glioblastoma using high resolution and contrast-enhanced MR imaging at 14.1 tesla. AB - To optimize the development of stem cell (SC)-based therapies for the treatment of glioblastoma (GBM), we compared the pathotropism of 2 SC sources, human mesenchymal stem cells (hMSCs) and fetal neural stem cells (fNSCs), toward 2 orthotopic GBM models, circumscribed U87vIII and highly infiltrative GBM26. High resolution and contrast-enhanced (CE) magnetic resonance imaging (MRI) were performed at 14.1 Tesla to longitudinally monitor the in vivo location of hMSCs and fNSCs labeled with the same amount of micron-size particles of iron oxide (MPIO). To assess pathotropism, SCs were injected in the contralateral hemisphere of U87vIII tumor-bearing mice. Both MPIO-labeled SC types exhibited tropism to tumors, first localizing at the tumor edges, then in the tumor masses. MPIO labeled hMSCs and fNSCs were also injected intratumorally in mice with U87vIII or GBM26 tumors to assess their biodistribution. Both SC types distributed throughout the tumor in both GBM models. Of interest, in the U87vIII model, areas of hyposignal colocalized first with the enhancing regions (ie, regions of high vascular permeability), consistent with SC tropism to vascular endothelial growth factor. In the GBM26 model, no rim of hyposignal was observed, consistent with the infiltrative nature of this tumor. Quantitative analysis of the index of dispersion confirmed that both MPIO-labeled SC types longitudinally distribute inside the tumor masses after intratumoral injection. Histological studies confirmed the MRI results. In summary, our results indicate that hMSCs and fNSCs exhibit similar properties regarding tumor tropism and intratumoral dissemination, highlighting the potential of these 2 SC sources as adequate candidates for SC-based therapies. PMID- 22670013 TI - Electronic cigarettes: no such thing as a free lunch...Or puff. PMID- 22670014 TI - The pharyngeal airway: is bigger really better? PMID- 22670015 TI - Role of the CHADS2 score in acute coronary syndromes: with or without atrial fibrillation. PMID- 22670016 TI - GRP78, intronic polymorphisms, and pharmacogenomics in non-small cell lung cancer. PMID- 22670017 TI - Point: should positive end-expiratory pressure in patients with ARDS be set on oxygenation? Yes. PMID- 22670018 TI - Counterpoint: should positive end-expiratory pressure in patients with ARDS be set based on oxygenation? No. PMID- 22670019 TI - Is there a Starling curve for intensive care? AB - Large differences exist in the provision of ICU beds worldwide, with a complicated mix of risks and benefits to the population of having either too few or too many beds. Having too few beds can result in delayed admission of patients to the ICU or no admission at all, with either scenario potentially increasing mortality. Potential societal benefits of having few beds include lower costs for health care and less futile intensive care at the end of life. With added ICU beds for a population, mortality benefit should accrue, but there is still the question of whether the addition of beds always means that more lives will be saved or whether there is a point at which no additional mortality benefit is gained. With an abundance of ICU beds may come the possibility of increasing harm in the forms of unnecessary costs, poor quality of deaths (ie, excessively intensive), and iatrogenic complications. The possibility of harm may be likened to the concept of falling off a Starling curve, which is traditionally used to describe worsening heart function when overfilling occurs. This commentary examines the possible implications of having too few or too many ICU beds and proposes the concept of a family of Starling curves as a way to conceptualize the balance of societal benefits and harms associated with different availability of ICU beds for a population. PMID- 22670021 TI - Whipple disease revealed by lung involvement: a case report and literature review. AB - We report the case of a man with a history of intermittent fever and arthritis who presented with a dry cough and associated lung involvement, who was eventually given the diagnosis of Whipple disease. The pulmonary symptoms preceded the development of GI manifestations. Five years later, periodic acid Schiff (PAS)-positive macrophages were identified in duodenal biopsy specimens and polymerase chain reaction for Tropheryma whipplei was positive in the duodenum, stools, saliva, and cerebrospinal fluid. Pulmonary T whipplei was retrospectively confirmed by positive PAS staining and immunoreactivity to specific antibodies in endobronchial biopsy specimens. Antibiotic treatment was followed by remission. A literature review identified eight other cases of Whipple disease presenting with lung parenchymal involvement, predominantly interstitial lung disease (ILD), and without initial GI symptoms. In the absence of GI symptoms, a diagnosis of Whipple disease should be considered in middle aged men presenting with ILD or lung nodules, if the patient has a history of unexplained arthralgia and/or fever. The association of mediastinal adenopathy or pleural effusion offers additional concern. Whipple disease may be fatal in the absence of treatment, but prolonged antibiotic treatment often leads to complete remission. PMID- 22670022 TI - The intersection of genes and environment: development of pulmonary arterial hypertension in a patient with hereditary hemorrhagic telangiectasia and stimulant exposure. AB - Pulmonary arterial hypertension (PAH) is a rare complication of hereditary hemorrhagic telangiectasia (HHT). The triggers that promote the development of PAH in HHT remain poorly understood. We present the case of a 45-year-old woman with decompensated right-sided heart failure secondary to newly diagnosed PAH. The clinical diagnosis of HHT was confirmed on the basis of recurrent spontaneous epistaxis, multiple typical mucocutaneous telangiectasia, and the presence of pulmonary arteriovenous malformation. There was also a suggestive family history. The patient was discovered to have active and extensive stimulant abuse in addition to HHT. We concluded that there may be a temporal relationship between exposure to stimulants and development of PAH in a host with underlying gene mutation. This case highlights the paradigm of PAH development after environmental exposure in a genetically susceptible host. PMID- 22670020 TI - Assessment and diagnosis of renal dysfunction in the ICU. AB - Identifying patients with impaired renal function is crucial in the setting of critical illness. Serum creatinine serves as the gold standard for assessing steady-state renal function, helping to define those with chronic kidney disease (CKD). Although these baseline creatinine values are often not available in the setting of critical illness, CKD, whether defined by serum creatinine or proteinuria, increases the risk of developing acute kidney injury (AKI). Despite delays in elevations following renal insults, serum creatinine remains the standard for assessing acute changes in renal function. Standardized definitions of AKI, using changes in serum creatinine and urine output, have informed the epidemiology of ICU-acquired AKI and have helped define the long-term outcomes in patients who experience AKI. A complex cyclical interplay exists between AKI and CKD, in which CKD predisposes patients to an increased risk of AKI, whereas those with AKI, regardless of baseline renal function, are more likely to suffer from post-AKI CKD. The clarification of the AKI-CKD dynamic remains a work in progress and will be aided by the implementation of novel measures of renal function. Several novel biomarkers of renal function have been proposed to augment serum creatinine in the diagnosis of AKI and CKD. These biomarkers, taken with recent clinical investigations, have laid the groundwork for the impending paradigm shift in risk stratifying and in diagnosing changes in renal function in the ICU. PMID- 22670023 TI - Neurocognitive impairment in obstructive sleep apnea. AB - Obstructive sleep apnea syndrome (OSAS) is a common disorder with far-reaching health implications. One of the major consequences of OSAS is an impact on neurocognitive functioning. Several studies have shown that OSAS has an adverse effect on inductive and deductive reasoning, attention, vigilance, learning, and memory. Neurocognitive impairment can be measured objectively with tests such as the Wechsler Adult Intelligence Scale-Revised, the Psychomotor Vigilance Task, the Steer Clear Performance Test, and tests of repetitive finger tapping. In children, OSAS may cause attention-deficit hyperactivity disorder in addition to behavioral problems and learning disabilities. Risk factors for cognitive impairment include increasing age, male sex, apolipoprotein E epsilon4 allele positivity, current cigarette smoking, obesity, hypertension, diabetes mellitus, metabolic syndrome, Down syndrome, hypothyroidism, significant alcohol consumption, stroke, and the use of psychoactive medications. At a cellular level, OSAS likely causes cognitive impairment through intermittent hypoxia, hormonal imbalance, and/or systemic inflammation, either independently or via the resultant endothelial dysfunction that occurs. Excessive daytime sleepiness should be measured and minimized in all studies of neurocognitive impairment. Recent studies have used functional and structural neuroimaging to delineate the brain areas affected in patients with OSAS with neurocognitive dysfunction. A common finding in several of these studies is decreased hippocampal volume. Other affected brain areas include the frontal and parietal lobes of the brain, which show focal reductions in gray matter. These changes can be reversed at least partially with the use of CPAP, which highlights the importance of early recognition and treatment of OSAS. The currently available data in this field are quite limited, and more research is needed. PMID- 22670024 TI - A 40-year-old man with a nodular lung disease and skin rash. PMID- 22670025 TI - A 49-year-old man with chest pain and fever after returning from France. PMID- 22670026 TI - A 64-year-old man with progressive dyspnea and cough productive of copious amounts of clear sputum. PMID- 22670027 TI - Documenting clinical and laboratory images in publications: the CLIP principles. AB - In scientific publications, laboratory and clinical images are part of the evidence on which authors base the interpretation and conclusions of their research. However, variability in biology, image acquisition and quality, standards for interpretation, training and experience of evaluators, and presence of artifacts can markedly reduce interrater and intrarater reliability. This variability in interpretation suggests that authors should support their claims with complete information about the image on which those claims are based. Yet, without appropriate guidelines, the documentation of these published images almost certainly will be incomplete and inconsistent. Here, we propose six principles for documenting clinical and laboratory images in publications: the clinical and laboratory images in publications (CLIP) principles. The principles were inspired by the CONSORT (Consolidated Standards of Reporting Trials) and related initiatives that are intended to improve the documentation of research through the use of guidelines. However, the CLIP principles are not formal guidelines, standards, or requirements but, rather, reminders about the information that may be needed to support interpretations and conclusions based on images. These principles organize the self-evident factors related to the nature, acquisition, reporting, and presentation of clinical and laboratory images. As imaging technologies become more complex, however, so too does the specific information needed to document how specific types of images are acquired. Thus, in addition to general direction for all authors, the CLIP principles give journals and professional societies a foundation, a direction, and some models to assist them in developing technology-specific guidelines for reporting the images common in their area of practice. PMID- 22670028 TI - Prolonged grief disorder in the next of kin of adult patients who die during or after admission to intensive care. PMID- 22670029 TI - Cognitive biases or inadequate searching? PMID- 22670030 TI - Obesity and mortality in critically ill patients: another case of the simpson paradox? PMID- 22670031 TI - Influence of obstructive sleep apnea on endothelial function in obese patients. PMID- 22670032 TI - Tetracaine's bad reputation is not well deserved. PMID- 22670033 TI - Early mobilization testing in patients with acute stroke. PMID- 22670034 TI - Learning curve for endobronchial ultrasound-guided transbronchial needle aspiration. PMID- 22670035 TI - Editorial commentary: Escherichia coli O104:H4 and hemolytic uremic syndrome: the analysis begins. PMID- 22670037 TI - Iron deficiency and malaria mortality: possible implication of invasive bacterial diseases. PMID- 22670036 TI - Recent introduction and rapid dissemination of Chikungunya virus and Dengue virus serotype 2 associated with human and mosquito coinfections in Gabon, central Africa. AB - BACKGROUND: Chikungunya virus (CHIKV) and Dengue virus serotype 2 (DENV-2) were recently introduced in central Africa, along with Aedes albopictus. Simultaneous outbreaks of CHIKV and DENV-2 have subsequently occurred, in Cameroon in 2006 and Gabon in 2007. METHODS: To study the spread of the 2 viruses, we conducted active surveillance of acute febrile syndromes throughout Gabon between 2007 and 2010. Diagnostic methods included quantitative real-time reverse-transcription polymerase chain reaction, and molecular characterization was based on partial envelope gene sequences. RESULTS: Between 2007 and 2010, 4287 acutely febrile patients were investigated for CHIKV and DENV-2 infections, of whom 1567 were CHIKV-positive, 376 DENV-2-positive, and 37 coinfected. We diagnosed 153 CHIKV and 11 DENV-2 cases in 2008, and 5 CHIKV and 9 DENV-2 cases in 2009. In 2010, CHIKV and DENV-2 caused a second large simultaneous outbreak. Among 2826 acutely febrile patients examined during this outbreak, 1112 were CHIKV-positive, 288 DENV-2-positive, and 28 coinfected. Mosquitoes were collected near the homes of coinfected patients, and 1 Aedes albopictus specimen was found to be positive for both CHIKV and DENV-2. CONCLUSIONS: These findings show the rapid dissemination of CHIKV and DENV-2 within a nonimmune population in a tropical African country, probably facilitated by the spread of Aedes albopictus. This has resulted in major simultaneous outbreaks with numerous coinfections in both human and mosquito. PMID- 22670038 TI - Transmission of infection with human allografts: essential considerations in donor screening. AB - Transmission of infection via transplantation of allografts including solid organs, eyes, and tissues are uncommon but potentially life-threatening events. Donor-derived infections have been documented following organ, tissue, and ocular transplants. Each year, more than 70 000 organs, 100 000 corneas, and 2 million human tissue allografts are implanted worldwide. Single donors may provide allografts for >100 organ and tissue recipients; each allograft carries some, largely unquantifiable, risk of disease transmission. Protocols for screening of organ or tissue donors for infectious risk are nonuniform, varying with the type of allograft, national standards, and availability of screening assays. In the absence of routine, active surveillance, coupled with the common failure to recognize or report transmission events, few data are available on the incidence of allograft-associated disease transmission. Research is needed to define the optimal screening assays and the transmissibility of infection with allografts. Approaches are reviewed that may contribute to safety in allograft transplantation. PMID- 22670039 TI - Hypercalcemia in disseminated coccidioidomycosis: expression of parathyroid hormone-related peptide is characteristic of granulomatous inflammation. AB - BACKGROUND: Hypercalcemia is an uncommon complication of disseminated granulomatous infections. The pathogenesis of hypercalcemia associated with infection is not clear. METHODS: We investigated a case of disseminated coccidioidomycosis with hypercalcemia. We used a sensitive radioimmunoassay to measure serum parathyroid hormone-related peptide (PTHrP) and a mouse monoclonal antibody to PTHrP to immunostain biopsies. RESULTS: We found elevated serum levels of PTHrP while the patient was hypercalcemic that became undetectable when serum calcium normalized. We also found that the inflammatory cells and some surrounding tissues in skin biopsies expressed PTHrP. PTHrP was expressed by all biopsied lesions of patients with coccidioidomycosis that we examined, whether localized to the lung or disseminated, but no other cases were hypercalcemic. PTHrP was also expressed by the 3 mycobacterial granulomas we examined, and in a lymph node from a patient with sarcoidosis. CONCLUSIONS: The expression of PTHrP is a property of infectious granulomas regardless of etiology or the tissue involved, suggesting that PTHrP expression is part of the normal granulomatous immune response. Hypercalcemia may result if there is disseminated infection and multiple granulomas. We propose that excess production of PTHrP is the cause of hypercalcemia in granulomatous infections. PMID- 22670040 TI - Role of the veterans aging cohort study index in assessing total atherosclerotic burden. PMID- 22670042 TI - Clinical manifestations of Cryptococcus gattii infection: determinants of neurological sequelae and death. AB - BACKGROUND: Longer-term morbidity and outcomes of Cryptococcus gattii infection are not described. We analyzed clinical, microbiological, and outcome data in Australian patients followed for 12 months, to identify prognostic determinants. METHODS: Culture-confirmed C. gattii cases from 2000 to 2007 were retrospectively evaluated. Clinical, microbiological, radiological, and outcome data were recorded at diagnosis and at 6 weeks, 6 months, and 12 months. Clinical and laboratory variables associated with mortality and with death and/or neurological sequelae were determined. RESULTS: Annual C. gattii infection incidence was 0.61 per 10(6) population. Sixty-two of 86 (72%) patients had no immunocompromise; 6 of 24 immunocompromised hosts had idiopathic CD4 lymphopenia, and 1 had human immunodeficiency virus/AIDS. Clinical and microbiological characteristics of infection were similar in immunocompromised and healthy hosts. Isolated lung, combined lung and central nervous system (CNS), and CNS only disease was reported in 12%, 51% and 34% of the cases, respectively. Complications in CNS disease included raised intracranial pressure (42%), hydrocephalus (30%), neurological deficits (27%; 6% developed during therapy) and immune reconstitutionlike syndrome (11%). Geometric mean serum cryptococcal antigen (CRAG) titers in CNS disease were 563.9 (vs 149.3 in isolated lung infection). Patient immunocompromise was associated with increased mortality risk. An initial cerebrospinal fluid CRAG titer of >=256 predicted death and/or neurological sequelae (P = .05). CONCLUSIONS: Neurological C. gattii disease predominates in the Australian endemic setting. Lumbar puncture and cerebral imaging, especially if serum CRAG titers are >=512, are essential. Long-term follow up is required to detect late neurological complications. Immune system evaluation is important because host immunocompromise is associated with reduced survival. PMID- 22670043 TI - An outbreak of Shiga toxin-producing Escherichia coli O104:H4 hemolytic uremic syndrome in Germany: presentation and short-term outcome in children. AB - BACKGROUND: In May and June 2011 the largest known outbreak of hemolytic uremic syndrome (HUS) occurred in northern Germany. Because, quite unusually, a large number of adults was affected and the causative Escherichia coli strain, serotype O104:H4, showed an atypical virulence factor pattern, it was speculated that this outbreak was associated with an aggressive course and an unfavorable prognosis also in children. METHODS: Retrospective analysis of medical records of 90 children and comparison to previous outbreak and sporadic case series. RESULTS: Median age was unusually high (11.5 years) compared with that in historical series. Only 1 patient (1.1%) died in the acute phase. Most patients (67/90 [74%]) received supportive care only. Renal replacement therapy was required in 64 of 90 (71%) of the children. Neurological complications, mainly seizures and altered mental stage, were present in 23 of 90 (26%) patients. Ten patients received plasmapheresis, 6 eculizumab, and 7 a combination of both. After a median follow-up of 4 months, renal function normalized in 85 of 90 (94%) patients, whereas 3 patients had chronic kidney disease stage 3 or 4, and 1 patient (1.1%) still requires dialysis. Complete neurological recovery occurred in 18 of 23 patients. Mild to moderate and major residual neurological changes were present in 3 patients and 1 patient, respectively, although all patients were still improving. CONCLUSIONS: E. coli O104:H4 caused the largest HUS outbreak in children reported in detail to date and most patients received supportive treatment only. Initial morbidity, as well as short-term outcome, due to this pathogen, is comparable to previous pediatric series of Shiga toxin producing E. coli HUS. PMID- 22670045 TI - Clinical scoring for risk of resistant organisms in pneumonia: right idea, wrong interpretation. PMID- 22670044 TI - Concurrent epidemics of skin and soft tissue infection and bloodstream infection due to community-associated methicillin-resistant Staphylococcus aureus. AB - BACKGROUND: Since its emergence in 2000, epidemic spread of the methicillin resistant Staphylococcus aureus (MRSA) clone USA300 has led to a high burden of skin and soft tissue infections (SSTIs) in the United States, yet its impact on MRSA bloodstream infections (BSIs) is poorly characterized. METHODS: To assess clonality of the MRSA isolates causing SSTI and BSI during the epidemic period, a stratified, random sample of 1350 unique infection isolates (from a total of 7252) recovered at the Community Health Network of San Francisco from 2000 to 2008 were selected for genotyping. Risk factors and outcomes for 549 BSI cases caused by the USA300 epidemic clone and non-USA300 MRSA clones were assessed by retrospective review of patient medical records. RESULTS: From 2000 to 2008, secular trends of USA300 SSTI and USA300 BSI were strongly correlated (Pearson r = 0.953). USA300 accounted for 55% (304/549) of BSIs as it was the predominant MRSA clone that caused community-associated (115/160), healthcare-associated community-onset (125/207), and hospital-onset (64/182) BSIs. Length of hospitalization after BSI diagnosis and mortality rates for USA300 and non-USA300 were similar. Two independent risk factors for USA300 BSI were identified: concurrent SSTI (adjusted relative risk, 1.4 [95% confidence interval {CI}, 1.2 1.6]) and anti-MRSA antimicrobial use in the preceding 30 days (0.7 [95% CI, .6 .8]). Isolates from concurrent SSTI were indistinguishable genotypically from the USA300 isolates that caused BSI. CONCLUSIONS: USA300 SSTIs serve as a source for BSI. Strategies to control the USA300 SSTI epidemic may lessen the severity of the concurrent USA300 BSI epidemic. PMID- 22670046 TI - Severe morbidity due to Opisthorchis viverrini and Schistosoma mekongi infection in Lao People's Democratic Republic. AB - We assessed morbidity due to Opisthorchis viverrini and Schistosoma mekongi infections in 243 individuals in Lao People's Democratic Republic. Morbidity was associated with O. viverrini infection intensity. Coinfection with S. mekongi resulted in excess risk of liver fibrosis and left liver lobe enlargement. The high public health impact of opisthorchiasis warrants control. PMID- 22670047 TI - Editorial commentary: seasonal influenza vaccines during the 2009 pandemic: help or harm? PMID- 22670048 TI - Vaccine administration decision making: the case of yellow fever vaccine. AB - BACKGROUND: Providers must counsel travelers to yellow fever (YF)-endemic areas, although risk estimates of disease and vaccine serious adverse events (SAEs) may be imprecise. The impact of risk information and patients' requests for participation in vaccine decisions on providers' recommendations is unknown. METHODS: Vaccine providers were surveyed regarding decisions for 4 patient scenarios before and after being presented information about risk of YF disease vs vaccine SAEs. Participants' theoretical attitudes were compared with actual responses to scenarios in which patients wanted to share vaccine decisions. Analyses were done by using chi(2) tests with significance level of .05. RESULTS: Forty-six percent of respondents made appropriate initial YF vaccine administration decisions for a pregnant woman, 73% for an immunosuppressed man, and 49% for an 8-month-old infant. After receiving scenario-specific information, 20%, 54%, and 23% of respondents respectively who initially responded incorrectly changed to a more appropriate decision. Thirty-one percent of participants made consistently appropriate decisions. Among participants who made >=1 incorrect decision, 35.7% made no decision changes after receiving information. In the scenario in which either a decision to withhold or to administer vaccine was acceptable, 19% of respondents refused a patient's request for vaccine. CONCLUSIONS: Targeted information is necessary but insufficient to change the process of vaccine administration decision making. Providers need additional education to enable them to apply evidence, overcome cognitive decision-making errors, and involve patients in vaccine decisions. PMID- 22670050 TI - Protective efficacy against pandemic influenza of seasonal influenza vaccination in children in Hong Kong: a randomized controlled trial. AB - BACKGROUND: The efficacy of seasonal influenza vaccination against 2009 pandemic influenza A(H1N1) remains unclear. METHODS: One child aged 6-17 years in each of 796 households was randomized to receive 2009-2010 seasonal trivalent inactivated influenza vaccine (TIV) or saline placebo between August 2009 and February 2010. Households were followed up with serology, symptom diaries, and collection of respiratory specimens during illnesses. The primary outcomes were influenza infection confirmed by reverse-transcription polymerase chain reaction (RT-PCR) or a >=4-fold rise in serum antibody titer measured by hemagglutination inhibition assay. RESULTS: Receipt of TIV led to 8-13-fold mean geometric rises in antibody titers against seasonal A and B viruses, but only 1.5-fold mean geometric rises against the pandemic A(H1N1) virus that was not included in the vaccine. Children who received TIV had a reduced risk of seasonal influenza B confirmed by RT-PCR, with a vaccine efficacy estimate of 66% (95% confidence interval [CI], 31%-83%). Children who received TIV also a had reduced risk of pandemic influenza A(H1N1) indicated by serology, with a vaccine efficacy estimate of 47% (95% CI, 15%-67%). CONCLUSIONS: Seasonal TIV prevented pandemic influenza A(H1N1) and influenza B infections in children. Pandemic A(H1N1) circulated at the time of vaccination and for a short time afterward with no substantial seasonal influenza activity during that period. The potential mechanism for seasonal TIV to provide protection, possibly short lived, for children against pandemic A(H1N1) infection despite poor cross-reactive serologic response deserves further investigation. Clinical Trials Registration. NCT00792051. PMID- 22670051 TI - Relevance of electrical remodeling in human atrial fibrillation: results of the Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial mechanisms of atrial fibrillation study. AB - BACKGROUND: In animal models of atrial fibrillation (AF), changes in atrial electrophysiological properties are associated with the development of AF. Their relevance to human AF is unclear. METHODS AND RESULTS: The Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial enrolled 2580 patients receiving a dual-chamber pacemaker, who were older than the age of 65 and had a history of hypertension, but no history of AF. Serial noninvasive electrophysiological testing was performed over 2 years in a subgroup of 485 patients. There were no differences in the clinical characteristics between patients with and those without device-detected atrial tachyarrhythmias during the first year. Patients with atrial tachyarrhythmias had longer paced (153+/-29 versus 145+/-28 ms; P=0.046) and sensed (128+/-46 versus 118+/-25 ms; P=0.06) P-wave durations and were more likely to have AF induced during electrophysiological testing (23.5% versus 13.6%; P=0.03). They had similar corrected sinus node recovery times at 90 bpm (388+/-554 versus 376 +/- 466 ms; P=0.86), atrial effective refractory periods at 90 bpm (250+/-32 versus 248+/-36 ms; P=0.70), and rate-adaptive shortening of the atrial effective refractory periods (14+/-13 versus 12+/-14 ms; P=0.11). There were no significant differences in the change in electrophysiological properties over 2 years between patients with and those without atrial tachyarrhythmias. CONCLUSIONS: Prolonged P-wave duration, but not differences in atrial effective refractory periods, was associated with the development of atrial tachyarrhythmias in pacemaker patients. PMID- 22670052 TI - Integrated computational and experimental analysis of the neuroendocrine transcriptome in genetic hypertension identifies novel control points for the cardiometabolic syndrome. AB - BACKGROUND: Essential hypertension, a common complex disease, displays substantial genetic influence. Contemporary methods to dissect the genetic basis of complex diseases such as the genomewide association study are powerful, yet a large gap exists between the fraction of population trait variance explained by such associations and total disease heritability. METHODS AND RESULTS: We developed a novel, integrative method (combining animal models, transcriptomics, bioinformatics, molecular biology, and trait-extreme phenotypes) to identify candidate genes for essential hypertension and the metabolic syndrome. We first undertook transcriptome profiling on adrenal glands from blood pressure extreme mouse strains: the hypertensive BPH (blood pressure high) and hypotensive BPL (blood pressure low). Microarray data clustering revealed a striking pattern of global underexpression of intermediary metabolism transcripts in BPH. The MITRA algorithm identified a conserved motif in the transcriptional regulatory regions of the underexpressed metabolic genes, and we then hypothesized that regulation through this motif contributed to the global underexpression. Luciferase reporter assays demonstrated transcriptional activity of the motif through transcription factors HOXA3, SRY, and YY1. We finally hypothesized that genetic variation at HOXA3, SRY, and YY1 might predict blood pressure and other metabolic syndrome traits in humans. Tagging variants for each locus were associated with blood pressure in a human population blood pressure extreme sample with the most extensive associations for YY1 tagging single nucleotide polymorphism rs11625658 on systolic blood pressure, diastolic blood pressure, body mass index, and fasting glucose. Meta-analysis extended the YY1 results into 2 additional large population samples with significant effects preserved on diastolic blood pressure, body mass index, and fasting glucose. CONCLUSIONS: The results outline an innovative, systematic approach to the genetic pathogenesis of complex cardiovascular disease traits and point to transcription factor YY1 as a potential candidate gene involved in essential hypertension and the cardiometabolic syndrome. PMID- 22670053 TI - Structural basis of histidine kinase autophosphorylation deduced by integrating genomics, molecular dynamics, and mutagenesis. AB - Signal transduction proteins such as bacterial sensor histidine kinases, designed to transition between multiple conformations, are often ruled by unstable transient interactions making structural characterization of all functional states difficult. This study explored the inactive and signal-activated conformational states of the two catalytic domains of sensor histidine kinases, HisKA and HATPase. Direct coupling analyses, a global statistical inference approach, was applied to >13,000 such domains from protein databases to identify residue contacts between the two domains. These contacts guided structural assembly of the domains using MAGMA, an advanced molecular dynamics docking method. The active conformation structure generated by MAGMA simultaneously accommodated the sequence derived residue contacts and the ATP-catalytic histidine contact. The validity of this structure was confirmed biologically by mutation of contact positions in the Bacillus subtilis sensor histidine kinase KinA and by restoration of activity in an inactive KinA(HisKA):KinD(HATPase) hybrid protein. These data indicate that signals binding to sensor domains activate sensor histidine kinases by causing localized strain and unwinding at the end of the C-terminal helix of the HisKA domain. This destabilizes the contact positions of the inactive conformation of the two domains, identified by previous crystal structure analyses and by the sequence analysis described here, inducing the formation of the active conformation. This study reveals that structures of unstable transient complexes of interacting proteins and of protein domains are accessible by applying this combination of cross-validating technologies. PMID- 22670054 TI - Spleen serves as a reservoir of osteoclast precursors through vitamin D-induced IL-34 expression in osteopetrotic op/op mice. AB - Osteoclasts are generated from monocyte/macrophage-lineage precursors in response to colony-stimulating factor 1 (CSF-1) and receptor activator of nuclear factor kappaB ligand (RANKL). CSF-1-mutated CSF-1(op/op) mice as well as RANKL(-/-) mice exhibit osteopetrosis (OP) caused by osteoclast deficiency. We previously identified RANKL receptor (RANK)/CSF-1 receptor (CSF-1R) double-positive cells as osteoclast precursors (OCPs), which existed in bone in RANKL(-/-) mice. Here we show that OCPs do not exist in bone but in spleen in CSF-1(op/op) mice, and spleen acts as their reservoir. IL-34, a newly discovered CSF-1R ligand, was highly expressed in vascular endothelial cells in spleen in CSF-1(op/op) mice. Vascular endothelial cells in bone also expressed IL-34, but its expression level was much lower than in spleen, suggesting a role of IL-34 in the splenic generation of OCPs. Splenectomy (SPX) blocked CSF-1-induced osteoclastogenesis in CSF-1(op/op) mice. Osteoclasts appeared in aged CSF-1(op/op) mice with up regulation of IL-34 expression in spleen and bone. Splenectomy blocked the age associated appearance of osteoclasts. The injection of 2-methylene-19-nor-(20S) 1alpha,25(OH)(2)D(3) (2MD), a potent analog of 1alpha,25-dihidroxyvitamin D(3), into CSF-1(op/op) mice induced both hypercalcemia and osteoclastogenesis. Administration of 2MD enhanced IL-34 expression not only in spleen but also in bone through a vitamin D receptor-mediated mechanism. Either splenectomy or siRNA mediated knockdown of IL-34 suppressed 2MD-induced osteoclastogenesis. These results suggest that IL-34 plays a pivotal role in maintaining the splenic reservoir of OCPs, which are transferred to bone in response to diverse stimuli, in CSF-1(op/op) mice. The present study also suggests that the IL-34 gene in vascular endothelial cells is a unique target of vitamin D. PMID- 22670055 TI - Dissociating activity in the lateral intraparietal area from value using a visual foraging task. AB - We make decisions about where to look approximately three times per second in normal viewing. It has been suggested that eye movements may be guided by activity in the lateral intraparietal area (LIP), which is thought to represent the relative value of objects in space. However, it is not clear how values for saccade goal selection are prioritized while free-viewing in a cluttered visual environment. To address this question, we compared the neural responses of LIP neurons in two subjects with their saccadic behavior and three estimates of stimulus value. These measures were extracted from the subjects' performance in a visual foraging task, in which we parametrically controlled the number of objects on the screen. We found that the firing rates of LIP neurons did not correlate well with the animals' behavior or any of our estimated measures of value. However, if the LIP activity was further normalized, it became highly correlated with the animals' decisions. These data suggest that LIP activity does not represent value in complex environments, but that the value can easily be extracted with one further step of processing. We propose that activity in LIP represents attentional priority and that the downstream normalization of this activity is an essential process in guiding action. PMID- 22670056 TI - Cell cycle- and DNA repair pathway-specific effects of apoptosis on tumor suppression. AB - The DNA damage response comprises DNA repair, cell-cycle checkpoint control, and DNA damage-induced apoptosis that collectively promote genomic integrity and suppress tumorigenesis. Previously, we have shown that the Chk2 kinase functions independently of the Mre11 complex (Mre11, Rad50, and Nbs1) and ATM in apoptosis and suppresses tumorigenesis resulting from hypomorphic alleles of Mre11 or Nbs1. Based on this work, we have proposed that Chk2 limits the oncogenic potential of replication-associated DNA damage. Here we further address the role of Chk2 and damage-induced apoptosis in suppressing the oncogenic potential of chromosome breaks. We show that loss of Chk2 or a mutation in p53 (R172P), which selectively impairs its function in apoptosis, rescued the lethality of mice lacking Lig4, a ligase required for nonhomologous end-joining (NHEJ) repair of DNA double-strand breaks in G0/G1. In contrast to Lig4(-/-)p53(-/-) mice, Lig4(-/-)Chk2(-/-) and Lig4(-/-)p53(R172P/R172P) mice were not prone to organ-specific, rapid tumorigenesis. Although the severe NHEJ deficiency of Lig4(-/-) was a less potent initiator of tumorigenesis in the p53(R172P/R172P) and Chk2(-/-) backgrounds, where p53 cell-cycle functions are largely intact, even mild defects in the intra S and G2/M checkpoints caused by mutations in Nbs1 are sufficient to influence malignancy in p53(R172P/R172P) mice. We conclude that the oncogenic potential of double-strand breaks resulting from NHEJ deficiency is highly restricted by nonapoptotic functions of p53, such as the G1/S checkpoint or senescence, suggesting that the particular facets of the DNA damage response required for tumor suppression are dictated by the proliferative status of the tumor initiating cell. PMID- 22670057 TI - Low-resolution solution structures of Munc18:Syntaxin protein complexes indicate an open binding mode driven by the Syntaxin N-peptide. AB - When nerve cells communicate, vesicles from one neuron fuse with the presynaptic membrane releasing chemicals that signal to the next. Similarly, when insulin binds its receptor on adipocytes or muscle, glucose transporter-4 vesicles fuse with the cell membrane, allowing glucose to be imported. These essential processes require the interaction of SNARE proteins on vesicle and cell membranes, as well as the enigmatic protein Munc18 that binds the SNARE protein Syntaxin. Here, we show that in solution the neuronal protein Syntaxin1a interacts with Munc18-1 whether or not the Syntaxin1a N-peptide is present. Conversely, the adipocyte protein Syntaxin4 does not bind its partner Munc18c unless the N-peptide is present. Solution-scattering data for the Munc18 1:Syntaxin1a complex in the absence of the N-peptide indicates that this complex adopts the inhibitory closed binding mode, exemplified by a crystal structure of the complex. However, when the N-peptide is present, the solution-scattering data indicate both Syntaxin1a and Syntaxin4 adopt extended conformations in complexes with their respective Munc18 partners. The low-resolution solution structure of the open Munc18:Syntaxin binding mode was modeled using data from cross linking/mass spectrometry, small-angle X-ray scattering, and small-angle neutron scattering with contrast variation, indicating significant differences in Munc18:Syntaxin interactions compared with the closed binding mode. Overall, our results indicate that the neuronal Munc18-1:Syntaxin1a proteins can adopt two alternate and functionally distinct binding modes, closed and open, depending on the presence of the N-peptide, whereas Munc18c:Syntaxin4 adopts only the open binding mode. PMID- 22670058 TI - The N-end rule pathway counteracts cell death by destroying proapoptotic protein fragments. AB - In the course of apoptosis, activated caspases cleave ~500 to ~1,000 different proteins in a mammalian cell. The dynamics of apoptosis involve a number of previously identified, caspase-generated proapoptotic protein fragments, defined as those that increase the probability of apoptosis. In contrast to activated caspases, which can be counteracted by inhibitor of apoptosis proteins, there is little understanding of antiapoptotic responses to proapoptotic protein fragments. One possibility is the regulation of proapoptotic fragments through their selective degradation. The previously identified proapoptotic fragments Cys RIPK1, Cys-TRAF1, Asp-BRCA1, Leu-LIMK1, Tyr-NEDD9, Arg-BID, Asp-BCL(XL), Arg BIM(EL), Asp-EPHA4, and Tyr-MET bear destabilizing N-terminal residues. Tellingly, the destabilizing nature (but not necessarily the actual identity) of N-terminal residues of proapoptotic fragments was invariably conserved in evolution. Here, we show that these proapoptotic fragments are short-lived substrates of the Arg/N-end rule pathway. Metabolic stabilization of at least one such fragment, Cys-RIPK1, greatly augmented the activation of the apoptosis inducing effector caspase-3. In agreement with this understanding, even a partial ablation of the Arg/N-end rule pathway in two specific N-end rule mutants is shown to sensitize cells to apoptosis. We also found that caspases can inactivate components of the Arg/N-end rule pathway, suggesting a mutual suppression between this pathway and proapoptotic signaling. Together, these results identify a mechanistically specific and functionally broad antiapoptotic role of the Arg/N end rule pathway. In conjunction with other apoptosis-suppressing circuits, the Arg/N-end rule pathway contributes to thresholds that prevent a transient or otherwise weak proapoptotic signal from reaching the point of commitment to apoptosis. PMID- 22670059 TI - Identification of beta-amyloid-binding sites on transthyretin. AB - Transthyretin (TTR) binds to the Alzheimer-related peptide beta-amyloid (Abeta), and may protect against Abeta-induced neurotoxicity. In this work, the specific domains on TTR involved with binding to Abeta were probed. An array was constructed of peptides derived from overlapping sequences from TTR. Strong binding of Abeta to TIAALLSPYSYS (residues 106-117) was detected, corresponding to strand G on the inner beta-sheet of TTR. Abeta bound weakly to four contiguous peptides spanning residues 59-83, which includes strand E through the E/F helix and loop. To further pinpoint specific residues on TTR involved with Abeta binding, nine alanine mutants were generated: I68A, I73A, K76A, L82A, I84A, S85A, L17A, T106A and L110A. Abeta binding was significantly inhibited only in L82A and L110A, indicating that Abeta binding to TTR is mediated through these bulky hydrophobic leucines. Abeta binding to L17A and S85A was significantly higher than to wild-type TTR. Enhancement of binding in L17A is postulated to arise from reduced steric restriction to the interior L110 site, since these two residues are adjacent in the native protein. The S85A mutation caused a reduction in TTR tetramer stability; increased Abeta binding is postulated to be a direct consequence of the reduced quaternary stability. PMID- 22670060 TI - TRINS: a method for gene modification by randomized tandem repeat insertions. AB - In nature, the evolution of new protein functions is driven not only by side chain substitutions (point mutations), but also by backbone modifications (insertions and deletions). The current laboratory diversification methods, however, are largely limited to point mutations. Of particular interest are short insertions-by-duplication that are frequent in nature but cannot be introduced in vitro in a library format (i.e. in random locations and lengths). Here, we describe a new procedure that allows the generation of tandem repeats of random fragments of the target gene via rolling-circle amplification, and the concurrent incorporation of these repeats into the target gene. This procedure, dubbed tandem repeat insertion, or TRINS, results in a library of genes carrying insertions-by-duplication of variable lengths (3-150 bp) at random positions. This diversification pattern allows sampling of sequence space regions that are not readily accessible by other protocols. We demonstrate this method by constructing three different gene libraries, and by selecting insertion variants of TEM-1 beta-lactamase. PMID- 22670061 TI - Impaired blood pressure variability in chronic fatigue syndrome--a potential biomarker. AB - INTRODUCTION: Autonomic dysfunction is common in chronic fatigue syndrome (CFS). This study set out to derive an autonomic biomarker using a comprehensive assessment of heart rate and blood pressure variability. METHODS: Heart rate and non-invasive continuous blood pressure measurements (task force monitor) at rest and on standing were performed in CFS (Fukuda n = 68) and matched controls (n = 68) to derive high frequency (HF; parasympathetic) and low frequency (LF; sympathetic) heart rate variability (HRV), systolic (SBPV) and diastolic (DBPV) blood pressure variability. Variables of significance were combined using receiver operator curves to explore the diagnostic utility of parameters particularly at rest. RESULTS: At rest, LF-HRV (sympathetic) was significantly increased in CFS compared to controls, while parasympathetic markers were significantly reduced (P = 0.006). Total DBP spectral power was increased (P = 0.0003) across all domains, with a shift towards sympathetic and away from parasympathetic SBPV (P = 0.05). On standing, overall SBPV response was significantly reduced with reductions in both sympathetic and parasympathetic components of SBPV (all P < 0.0001). Change in LF-DBP and relative balance of LF/HF DBP on standing differed between CFS and controls (P < 0.0001). Using the 85% sensitivity levels, we determined a threshold for three chosen resting BPV parameters of LF DBP >3.185, rest HF DBP >0.86, rest total DBP >7.05. Achieving all of these differentiated between CFS and controls with 77% sensitivity and 53% specificity. CONCLUSION: This study has shown that there are objectively measured abnormalities of blood pressure variability in CFS and that these abnormalities have the potential to be a bedside diagnostic tool. PMID- 22670062 TI - A shocking hematuria. PMID- 22670063 TI - Cognitive decline reversed by cinacalcet. PMID- 22670064 TI - Combinatorial growth of oxide nanoscaffolds and its influence in osteoblast cell adhesion. AB - We report a novel method for high-throughput investigations on cell-material interactions based on metal oxide nanoscaffolds. These scaffolds possess a continuous gradient of various titanium alloys allowing the compositional and morphological variation that could substantially improve the formation of an osseointegrative interface with bone. The model nanoscaffold has been fabricated on commercially pure titanium (cp-Ti) substrate with a compositional gradients of tin (Sn), chromium (Cr), and niobium (Nb) deposited using a combinatorial approach followed by annealing to create native oxide surface. As an invitro test system, the human fetal osteoblastic cell line (hFOB 1.19) has been used. Cell adhesion of hFOB 1.19 cells and the suitability of these alloys have been evaluated for cell-morphology, cell-number, and protein adsorption. Although, cell-morphology was not affected by surface composition, cell-proliferation rates varied significantly with surface metal oxide composition; with the Sn- and Nb rich regions showing the highest proliferation rate and the Cr-rich regions presenting the lowest. The results suggest that Sn and Nb rich regions on surface seems to promote hFOB 1.19 cell proliferation and may therefore be considered as implant material candidates that deserve further analysis. PMID- 22670071 TI - Age and retinal nerve fiber layer thickness measured by spectral domain optical coherence tomography. AB - PURPOSE: To evaluate the association between age and peripapillary retinal nerve fiber layer (RNFL) thickness measured by Cirrus high-definition (HD) spectral domain optical coherence tomography (OCT) in healthy Korean subjects. METHODS: A total of 302 eyes from 155 healthy Korean subjects (age range, 20 to 79 years) underwent RNFL thickness measurements using the Cirrus HD-OCT. Average, quadrant, and clock-hour RNFL thickness parameters were analyzed in terms of age using linear mixed effect models. RESULTS: Average RNFL demonstrated a slope of -2.1 um per decade of age (p < 0.001). In quadrant analysis, superior (-3.4 um/decade, p < 0.001) and inferior (-2.9 um/decade, p < 0.001) quadrants showed steeper slopes, whereas temporal (-1.1 um/decade, p < 0.001) and nasal (-1.0 um/decade, p < 0.001) quadrants revealed shallower slopes. Among the 12 clock-hour sectors, clock hours 6 (-4.5 um/decade, p < 0.001) and 1 (-4.1 um/decade, p < 0.001) showed the greatest tendency to decline with age; RNFLs of the 3 (-0.2 um/decade, p = 0.391) and 4 (-0.6 um/decade, p = 0.052) o'clock hour sectors did not show significant decay. CONCLUSIONS: RNFL thickness was associated with age, especially in superior and inferior areas. The topographic distribution of correlation between age and RNFL thickness was not uniform. PMID- 22670072 TI - Factors associated with the signal strengths obtained by spectral domain optical coherence tomography. AB - PURPOSE: The aim of this study was to investigate factors associated with the signal strengths (SS, image quality scores) of optic disc and macular images obtained using Cirrus spectral domain optical coherence tomography (OCT). METHODS: Ninety-two glaucomatous eyes were imaged using the Cirrus OCT macular and optic disc cube modes after pupil dilation. The influences of patient age, spherical equivalent, cataract presence, and cataract and glaucoma severity (visual field mean deviation), on the SS of images obtained using the two cube modes were compared between patients whose images showed high SS (SS >=7) and low SS (SS <7). RESULTS: The signal strength was significantly higher in images obtained using the macular cube compared to the optic disc cube mode (7.8 +/- 1.3 vs. 6.9 +/- 1.1, respectively; p = 0.001). Age and visual acuity of patients differed significantly between the high- and low-SS groups when data acquired using the optic disc (p = 0.027 and 0.012, respectively) and macular cube modes (p = 0.046 and 0.014, respectively) were analyzed. When the optic disc cube mode was employed, the extent of cataracts was significantly related to SS, whereas when the macular cube mode was used, none of the factors analyzed was significantly associated with SS. CONCLUSIONS: Age, visual acuity, and the extent of cataracts were significantly associated with images of higher SS when the Cirrus OCT optic disc cube mode was employed. PMID- 22670070 TI - Short-term effectiveness of intravitreal bevacizumab vs. ranibizumab injections for patients with polypoidal choroidal vasculopathy. AB - PURPOSE: To compare the effectiveness of intravitreal injections of bevacizumab and ranibizumab in patients with treatment-naive polypoidal choroidal vasculopathy (PCV). METHODS: Records from 106 consecutive patients who received intraviteral bevacizumab (n = 58, 1.25 mg) or ranibizumab (n = 52, 0.5 mg) for treatment of PCV were retrospectively reviewed. After three initial monthly loading injections, injection was performed as needed. The main outcome measures included best-corrected visual acuity (BCVA), foveal central thickness (FCT) as assessed by spectral domain optical coherence tomography, and the changes in polypoidal lesions based on an indocyanine green angiography. RESULTS: The average number of injections was 3.31 +/- 1.25 in the bevacizumab group and 3.44 +/- 0.92 in the ranibizumab group. Mean logarithm of the minimum angle of resolution of BCVA from baseline to 6 months after injection improved by 0.17 in the bevacizumab group (p = 0.03) and by 0.19 in the ranibizumab group (p = 0.01). Average FCT decreased from 322 +/- 62.48 um to 274 +/- 40.77 um in the bevacizumab group (p = 0.02) and from 338 +/- 50.79 um to 286 +/- 36.93 um in the ranibizumab group (p = 0.02). Polyp regression rate was 20.7% (12 of 58 eyes) in the bevacizumab group and 21.2% (11 of 52 eyes) in the ranibizumab group. There was no statistically significant difference between groups in BCVA improvement achieved, FCT improvement achieved, and polyp regression rate between groups. CONCLUSIONS: Intravitreal injections of bevacizumab and ranibizumab have similar effects in stabilizing of visual acuity, macular edema, and regression of polypoidal complex in PCV eyes over the short term. PMID- 22670073 TI - Glaucoma progression detection by retinal nerve fiber layer measurement using scanning laser polarimetry: event and trend analysis. AB - PURPOSE: To evaluate the use of scanning laser polarimetry (SLP, GDx VCC) to measure the retinal nerve fiber layer (RNFL) thickness in order to evaluate the progression of glaucoma. METHODS: Test-retest measurement variability was determined in 47 glaucomatous eyes. One eye each from 152 glaucomatous patients with at least 4 years of follow-up was enrolled. Visual field (VF) loss progression was determined by both event analysis (EA, Humphrey guided progression analysis) and trend analysis (TA, linear regression analysis of the visual field index). SLP progression was defined as a reduction of RNFL exceeding the predetermined repeatability coefficient in three consecutive exams, as compared to the baseline measure (EA). The slope of RNFL thickness change over time was determined by linear regression analysis (TA). RESULTS: Twenty-two eyes (14.5%) progressed according to the VF EA, 16 (10.5%) by VF TA, 37 (24.3%) by SLP EA and 19 (12.5%) by SLP TA. Agreement between VF and SLP progression was poor in both EA and TA (VF EA vs. SLP EA, k = 0.110; VF TA vs. SLP TA, k = 0.129). The mean (+/-standard deviation) progression rate of RNFL thickness as measured by SLP TA did not significantly differ between VF EA progressors and non-progressors (-0.224 +/- 0.148 um/yr vs. -0.218 +/- 0.151 um/yr, p = 0.874). SLP TA and EA showed similar levels of sensitivity when VF progression was considered as the reference standard. CONCLUSIONS: RNFL thickness as measurement by SLP was shown to be capable of detecting glaucoma progression. Both EA and TA of SLP showed poor agreement with VF outcomes in detecting glaucoma progression. PMID- 22670074 TI - Low limit for effective signal strength in the Stratus OCT in imperative low signal strength cases. AB - PURPOSE: To determine the lowest limit of signal strength that is still effective for accurate analysis of optic coherence tomography (OCT) values, we investigated the reproducibility of OCT scans by signal strength (SS). METHODS: A total of 668 subjects were scanned for measurements of retinal nerve fiber layer (RNFL) thickness using the Stratus OCT twice on the same day. The variability of overall RNFL thickness parameters obtained at different SS was analyzed and compared by repeated-measures of ANOVA and Spearman's correlation coefficient. Values of the intraclass correlation coefficient (ICC) and variability (standard deviation) of RNFL thickness were obtained. The false positive ratio was analyzed. RESULTS: When SS was 3, the variability of RNFL thickness was significantly different (low ICC, high variability) in comparison to when SS was 4 or greater. Significant negative correlations were observed between variability in RNFL thickness and signal strength. The difference of variability of average RNFL thickness between SS 4 (4.94 um) and SS 6 (4.41 um) was 0.53 um. CONCLUSIONS: Clinically, the difference of variability of average RNFL thickness between SS 4 and SS 6 was quite small. High SS is important, however, when signal strength is low due to uncorrectable factors in patients in need of OCT for glaucoma and retinal disease. Our results suggest that SS 4 is the lowest acceptable limit of signal strength for obtaining reproducible scanning images. PMID- 22670076 TI - Contemplation of the surgical normogram of lateral rectus recession for exotropia associated with superior oblique palsy. AB - PURPOSE: To suggest a surgical normogram for lateral rectus recession in exotropia associated with unilateral or bilateral superior oblique muscle palsy (SOP). METHODS: We retrospectively reviewed the charts of 71 patients with exotropia who were successfully corrected over one year. Each patient had undergone unilateral or bilateral rectus recession associated with uni- or bilateral inferior oblique (IO) 14 mm recession, using a modified surgical normogram for lateral rectus (LR) recession, which resulted in 1 to 2 mm of reduction of LR recession. We divided all patients into 2 groups, the 34 patients who had undergone LR recession with unilateral IO (UIO) recession group and the remaining 37 patients who had undergone LR recession with bilateral IO (BIO) recession group. Lateral incomitancy was defined when the exoangle was reduced by more than 20% compared to the primary gaze angle. The surgical effects (prism diopters [PD]/mm) of LR recession were compared between the two groups using the previous surgical normogram as a reference (Parks' normogram). RESULTS: The mean preoperative exodeviation was 20.4 PD in the UIO group and 26.4 PD in the BIO group. The recession amount of the lateral rectus muscle ranged from 4 to 8.5 mm in the UIO group and 5 to 9 mm in the BIO group. Lateral incomitancy was noted as 36.4% and 70.3% in both groups, respectively (p = 0.02). The effect of LR recession was 3.23 +/- 0.84 PD/mm in the UIO group and 2.98 +/- 0.62 PD/mm in the BIO group and there was no statistically significant difference between two the groups (p = 0.15). CONCLUSIONS: Reduction of the LR recession by about 1 to 2 mm was successful and safe to prevent overcorrection when using on IO weakening procedure, irrespective of the laterality of SOP. PMID- 22670075 TI - Bell's phenomenon during screening examination for retinopathy of prematurity. AB - PURPOSE: Bell's phenomenon (BP), which may disturb screening examinations for retinopathy of prematurity (ROP), is known to present infrequently in premature babies. Stress associated with the examinations can influence expression of BP. The authors of the present study evaluated BP during examinations for ROP. METHODS: The present study included 102 eyes of 51 premature babies. Expression of BP was assessed at 3 steps of the examination in the following order: after insertion of a speculum, after illumination of an indirect ophthalmoscope and after scleral depression. The relationship between the expression of BP and the gestational age at the examination was analyzed in each step of the examination. RESULTS: The frequency of BP after the speculum insertion and the illumination was 77% to 92% in infants 32 weeks of age or younger, and decreased significantly to 16% to 57% in infants 42 weeks of age or older (p < 0.005). BP after the scleral depression had no significant association with the gestational age. Frequency of BP increased significantly as the steps of the examination proceeded (p < 0.01). CONCLUSIONS: BP was frequent in premature infants during ROP examination in spite of neurological immaturity. The examiner should take BP into consideration, which frequently occurs in younger infants. PMID- 22670077 TI - Factors associated with the direction of ocular deviation in sensory horizontal strabismus and unilateral organic ocular problems. AB - PURPOSE: To evaluate factors associated with the direction of horizontal deviation in the sensory strabismus of patients with unilateral organic amblyopia. METHODS: The medical charts of 53 patients who had been diagnosed with sensory strabismus between 2000 and 2009 were reviewed retrospectively. The underlying ocular disease, time of onset and the duration of vision impairment, refractive error and axial length of the fixing eye, and the direction and angle of deviation were analyzed to determine the distribution of underlying diseases and any factors relevant to determining the direction of the horizontal deviation. RESULTS: Congenital cataracts were the most common underlying disease, found in 33 patients, followed by acquired cataracts, optic nerve disorders, retinal detachment, glaucoma and lens subluxation. Among the 50 patients with horizontal strabismus, 11 had esotropia and 39 had exotropia. The incidence of esotropia was significantly higher when the fixing eye had hyperopia or emmetropia, than when the eye was myopic. Age of onset of vision deterioration and at diagnosis of sensory strabismus, and the axial length of the fixing eye had no relationship to the direction of horizontal deviation. In addition, the duration of visual impairment had no significant relationship with the direction or extent of horizontal deviation. CONCLUSIONS: The most common cause of sensory strabismus was congenital cataracts and the most frequent type of strabismus was exotropia. With respect to the direction of horizontal strabismus, esotropia occurred significantly more often when the refractive error of the fixing eye was hyperopia or emmetropia than when the fixing eye was myopic. PMID- 22670078 TI - Expression of the Na+-K+-2Cl(-)-cotransporter 2 in the normal and pressure induced ischemic rat retina. AB - PURPOSE: To evaluate the expression of the Na(+)-K(+)-2Cl(-)-cotransporter 2 (NKCC2) in the ischemic rat retina. METHODS: Retinal ischemia was induced by pressures 90 to 120 mmHg, above systemic systolic pressure. Immunohistochemistry and western blot analysis were performed. RESULTS: NKCC2 is expressed in the normal retina and its expression is increased by ischemia caused by intraocular pressure elevation. NKCC2 immunoreactivity was observed mainly in axon bundles of ganglion cells and horizontal cell processes in the retina. NKCC2 expression continuously increased with a peak value 3 days (to 415% of normal levels) after ischemic injury, and then gradually decreased to 314% of controls until 2 weeks post injury. The mean density of NKCC2-labeled ganglion cells per mm(2) changed from 1,255 +/- 109 in normal retinas to 391 +/- 49 and 185 +/- 37 at 3 days and 2 weeks after ischemia, respectively (p < 0.05), implying cell death of ganglion cells labeled with NKCC2. CONCLUSIONS: Taken together, these results suggest that NKCC2, which is expressed in retinal ganglion and horizontal cells, may contribute to cell death by ischemic injury in the retina, although the molecular mechanisms involved remain to be clarified. PMID- 22670079 TI - Frontoethmoidal mucocele presenting as progressive enophthalmos. AB - In this case report we describe a 27-year-old man who presented with progressive enophthalmos for 5 months without any other associated ocular symptoms such as pain, diplopia, or visual disturbance. Computed tomography showed that his progressive enophthalmos originated from a frontoethmoidal mucocele and this caused destruction of the lamina papyracea and shrinkage of the ethmoidal air cell. Finally the enlarged orbital space caused an inward deviation of the eyeball. Endoscopic marsupialization was successfully performed by an otolaryngologist and did not result in any ophthalmologic sequelae. Although frontoethmoidal sinus mucoceles mostly frequently originates from orbital mucoceles, enophthalmic manifestations are very rare. Enophthalmic conditions are not as responsive to surgical interventions as exophthalmic conditions. PMID- 22670080 TI - Unusual involvement of IgG4-related sclerosing disease in lacrimal and submandibular glands and extraocular muscles. AB - Chronic sclerosing sialadenitis, also known as Kuttner tumor, is a chronic inflammatory disease of the salivary glands that is reported in a few cases in medical literature. Recent reports suggest that certain aspects of sclerosing diseases, including chronic sclerosing sialadenitis or dacryoadenitis, should be classified under immunoglobulin G4 (IgG4)-related sclerosing disease based on immunohistochemical studies. This study reports an unusual case of IgG4-related sclerosing disease appearing simultaneously in the lacrimal glands, submandibular glands, and extraocular muscles. A 56-year-old male presented with complaints of bilateral eyelid swelling and proptosis that began two years ago. Computed tomography confirmed that bilateral submandibular enlargements also existed five years ago in the subject. Orbital computed tomography and magnetic resonance imaging revealed bilateral lacrimal gland enlargement and thickening of extraocular muscles. Typical findings of chronic sclerosing dacryoadenitis were revealed upon pathologic exam of the right lacrimal gland. Immunostaining revealed numerous IgG4-positive plasma cells. Through these clinical features, we make a diagnosis of IgG4-relataed sclerosing disease in the subject. PMID- 22670081 TI - LASIK interface-captured foreign bodies after mild traumatic corneal scratch without flap displacement. AB - A 38-year-old woman developed diffusely distributed opacities with crystalline materials in the laser in situ keratomileusis (LASIK) interface of her eye after she was scratched by a sprig during mountain climbing. No sign of flap displacement was noted. Despite two days of topical and systemic antibiotics therapy, the corneal infiltration with interface opacities persisted. The following day, the distribution of the crystalline materials had rotated in a counterclockwise direction. Flap lifting and foreign body removal using sufficient irrigation were performed. One month after surgery, the patient's postoperative uncorrected visual acuity was 0.8 with cleared interface. No signs of epithelial ingrowth or flap striae were noted. Mild traumatic corneal scratching without flap displacement may threaten the integrity of the LASIK interface. If foreign bodies are suspected to be the cause of inflammation, early flap lifting with irrigation is imperative for successful treatment. PMID- 22670082 TI - Sequential intrastromal corneal ring implantation and cataract surgery in a severe keratoconus patient with cataract. AB - A 49-year-old man with an uncorrected visual acuity (UCVA) of 20 / 1000, a best spectacle-corrected visual acuity (BSCVA) of 20 / 400, keratometric readings of K1 = 59.88 * 82 degrees / K2 = 45.88 * 172 degrees , and an inferior steepening that was consistent with keratoconus in his left eye was treated with clear cornea phacoemulsification and an intraocular lens (IOL) implantation after insertion of keraring intrastromal corneal ring segments for severe keratoconus and cataract. An asymmetrical pair of kerarings was implanted with the assistance of a femtosecond laser in September 2008; the one segment was 250 um and the other was 150 um and both were placed at 70 degrees . Three months after the kerarings were implanted, clear-cornea phacoemulsification and IOL implantation were performed on the left eye. After surgery, both the UCVA and the BSCVA of the left eye improved by eight lines. Postoperative central keratometry showed a decrease of 7.35 diopters in the left eye. Both the postoperative refraction ( 0.75 -0.75 * 60 degrees ) and the keratometric reading (K1 = 50.05 * 93 degrees / K2 = 48.83 * 3 degrees ) remained stable one month following the procedures. Thus, the sequential order of intrastromal corneal rings implantation and cataract surgery can be considered as a treatment option in patients with severe keratoconus and cataract. PMID- 22670083 TI - Indocyanine green angiographic findings of obscure choroidal abnormalities in neurofibromatosis. AB - We report two cases of choroidal neurofibromatosis, detected with the aid of indocyanine green angiography (ICGA) in patients with neurofibromatosis (NF)-1, otherwise having obscure findings based on ophthalmoscopy and fluoresceine angiography (FA). In case 1, the ophthalmoscopic exam showed diffuse bright or yellowish patched areas with irregular and blunt borders at the posterior pole. The FA showed multiple hyperfluorescent areas at the posterior pole in the early phase, which then showed more hyperfluorescence without leakage or extent in the late phase. The ICGA showed diffuse hypofluorescent areas in both the early and late phases, and the deep choroidal vessels were also visible. In case 2, the fundus showed no abnormal findings, and the FA showed weakly hypofluorescent areas with indefinite borders in both eyes. With the ICGA, these areas were more hypofluorescent and had clear borders. Choroidal involvement in NF-1 seems to occur more than expected. In selected cases, ICGA is a useful tool to be utilized when an ocular examination is conducted in a patient that has no definite findings based on the ophthalmoscope, B-scan, or FA tests. PMID- 22670084 TI - Anterior ischemic optic neuropathy associated with udenafil. AB - We report a case of anterior ischemic optic neuropathy associated with udenafil. A 54-year-old male presented with an acute onset visual field defect of the right eye after udenafil use. Examination revealed a relative afferent pupillary defect and a swollen disc. Automated visual fields revealed an enlarged blind spot and a narrowed visual field. Fluorescein angiography revealed both an inferior choroidal filling delay and an inferior sector filling delay of the optic disc in the arteriovenous phase as well as diffuse leakage of the optic disc in the late phase. Optical coherent tomography revealed increased thickness of the retinal nerve fiber layer, especially in the area of the inferior disc. The patient was counseled to discontinue the use of udenafil and to monitor his blood pressure regularly. The disc swelling was resolved with residual optic atrophy one month after discontinuing the use of udenafil. PMID- 22670085 TI - Quantitative analysis of optic disc color. PMID- 22670086 TI - Update in medical education for pediatrics: insights and directions from the 2010 literature. AB - BACKGROUND: While most would agree that utilizing the literature to enhance individual educational practice and/or institutional success is the ideal method for improving medical education, methods to focus attention on the most relevant and valuable information have been heretofore lacking in the pediatric medical education literature. METHODS: We performed a review of the medical education literature for the year 2010. Utilizing a similar strategy employed by others in Internal Medicine, we selected 12 high-yield education journals and manually reviewed the table of contents to select titles that would have grassroots applicability for medical educators. A broad search through PubMed was then completed using search terms adopted from prior studies, and titles from this search were similarly selected. The abstracts of selected titles (n=147) were each reviewed by two of the authors, then all authors reached consensus on articles for full review (n=34). The articles were then discussed and scored to achieve consensus for the 11 articles for inclusion in this paper. RESULTS: Several themes emerged from reviewing these publications. We did not select topics or sections of interest a priori. The themes, grouped into four areas: supervision and leadership, hand-off communication, core competencies: teaching and assessment, and educational potpourri, reflect our community's current concerns, challenges, and engagement in addressing these topics. Each article is summarized below and begins with a brief statement of what the study adds to the practice of pediatric medical education. DISCUSSION: This review highlights multiple 'articles of value' for all medical educators. We believe the value of these articles and the information they contain for improving the methods used to educate medical students, residents, and fellows are significant. The organically derived thematic areas of the representative articles offer a view of the landscape of medical education research in pediatrics in 2010. Readers can use these individual articles as both tools to improve their practice, as well as inspiration for future areas of research. PMID- 22670087 TI - Improving year-end transfers of care in academic ambulatory clinics: a survey of pediatric resident physician perceptions. AB - BACKGROUND: In resident primary care continuity clinics, at the end of each academic year, continuity of care is disrupted when patients cared for by the graduating class are redistributed to other residents. Yet, despite the recent focus on the transfers of care between resident physicians in inpatient settings, there has been minimal attention given to patient care transfers in academic ambulatory clinics. We sought to elicit the views of pediatric residents regarding year-end patient handoffs in a pediatric resident continuity clinic. METHODS: Residents assigned to a continuity clinic of a large pediatric residency program completed a questionnaire regarding year-end transfers of care. RESULTS: Thirty-one questionnaires were completed out of a total 45 eligible residents (69% response). Eighty seven percent of residents strongly or somewhat agreed that it would be useful to receive a written sign-out for patients with complex medical or social issues, but only 35% felt it would be useful for patients with no significant issues. Residents more frequently reported having access to adequate information regarding their new patients' medical summary (53%) and care plan (47%) than patients' functional abilities (30%), social history (17%), or use of community resources (17%). When rating the importance of receiving adequate sign-out in each those domains, residents gave most importance to the medical summary (87% of residents indicating very or somewhat important) and plan of care (84%). Residents gave less importance to receiving sign-out regarding their patients' functional abilities (71%) social history (58%), and community resources (58%). Residents indicated that lack of access to adequate patient information resulted in additional work (80%), delays or omissions in needed care (56%), and disruptions in continuity of care (58%). CONCLUSIONS: In a single-site study, residents perceive that they lack adequate information during year-end patient transfers, resulting in potential negative consequences for patient safety and medical education. PMID- 22670088 TI - Toward a portrait of Canadian cancer control. PMID- 22670089 TI - The tip of the iceberg: a countercurrents series. PMID- 22670090 TI - Risk factors and early detection of breast cancer: facts, questions, and genome based perspectives. PMID- 22670091 TI - Pereira's attack on legalizing euthanasia or assisted suicide: smoke and mirrors. AB - OBJECTIVE: To review the empirical claims made in: Pereira J. Legalizing euthanasia or assisted suicide: the illusion of safeguards and controls. Curr Oncol 2011;18:e38-45. DESIGN: We collected all of the empirical claims made by Jose Pereira in "Legalizing euthanasia or assisted suicide: the illusion of safeguards and controls." We then collected all reference sources provided for those claims. We compared the claims with the sources (where sources were provided) and evaluated the level of support, if any, the sources provide for the claims. We also reviewed other available literature to assess the veracity of the empirical claims made in the paper. We then wrote the present paper using examples from the review. RESULTS: Pereira makes a number of factual statements without providing any sources. Pereira also makes a number of factual statements with sources, where the sources do not, in fact, provide support for the statements he made. Pereira also makes a number of false statements about the law and practice in jurisdictions that have legalized euthanasia or assisted suicide. CONCLUSIONS: Pereira's conclusions are not supported by the evidence he provided. His paper should not be given any credence in the public policy debate about the legal status of assisted suicide and euthanasia in Canada and around the world. PMID- 22670092 TI - Casting stones and casting aspersions: let's not lose sight of the main issues in the euthanasia debate. PMID- 22670093 TI - Assisted death and the slippery slope-finding clarity amid advocacy, convergence, and complexity. AB - This paper unpacks the slippery slope argument as it pertains to assisted death.The assisted-death regimes of the Netherlands, Belgium, Luxembourg, Switzerland, and the states of Washington and Oregon are discussed and examined with respect to the slippery slope analytical rubric. In addition to providing a preliminary explanation of how the slippery slope argument has been academically defined and constructed, the paper examines assisted-death models from the perspective of considering what might exist at the top and at the bottom of the slippery slope. It also explores the nature and scope of safeguards implemented to avoid slippage, and shows that what lies at the top and bottom of the slippery slope may be different from jurisdiction to jurisdiction. After identifying some of the recent concerns that have arisen within each of the jurisdictions (concerns that might be viewed by some as evidence of slide), the paper concludes by making note of certain critical issues in the current assisted-death debate that merit deeper examination. PMID- 22670094 TI - Fertility risk discussions in young patients diagnosed with colorectal cancer. AB - PURPOSE: In 2006, the American Society of Clinical Oncology established guidelines on fertility preservation in cancer patients, but recent data suggest that the guidelines are not widely followed. To identify the frequency of fertility discussions and the characteristics that influence the rate of discussion, we performed a retrospective chart review for patients less than 40 years of age with newly diagnosed colorectal cancer (CRC). METHODS: Charts of patients aged 18-40 years with newly diagnosed crc presenting to the Juravinski Cancer Centre from 2000 to 2009 were reviewed for documentation of discussions regarding fertility risks with treatment and reproductive options available. The influences of sex, age, year of diagnosis, stage of cancer, and type of treatment on the frequency of discussions were explored. RESULTS: The review located 59 patients (mean age: 35 years) who met the criteria for inclusion. A fertility discussion was documented in 20 of those patients [33.9%; 95% confidence interval (CI): 22.1% to 47.4%]. In the multivariate analysis, the odds of fertility being addressed was higher for patients receiving radiation [odds ratio (OR): 9.31; 95% ci: 2.49 to 34.77, p < 0.001) and lower by age (OR: 0.86; 95% ci: 0.74 to 0.99; p = 0.040). Of patients less than 35 years of age undergoing radiation treatment, 85% had a documented fertility discussion. We observed no significant difference in the frequency of discussions after 2006, when the American Society of Clinical Oncology guidelines were published (31.4% for 2000-2006 vs. 37.5% for 2007-2009, p = 0.63). CONCLUSIONS: Discussions about fertility risks associated with CRC treatment occur infrequently among young adults with newly diagnosed CRC. However, discussions occur more frequently in younger patients and in those undergoing radiation. Further investigations assessing barriers and physician attitudes to fertility risk discussion and reproductive options are planned. PMID- 22670095 TI - A Canadian perspective on bendamustine for the treatment of chronic lymphocytic leukemia and non-Hodgkin lymphoma. AB - Despite the success of standard treatments in chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL), patients are often unable to tolerate aggressive regimens, and they require effective alternatives. Bendamustine is a bifunctional alkylator with unique properties that significantly distinguish it from other agents in its class. In untreated CLL, bendamustine has demonstrated rates of response and progression-free survival (PFS) that are superior to those with chlorambucil, with an acceptable toxicity profile. In the relapsed setting, combination treatment with bendamustine-rituximab (BR) has demonstrated promising activity in high-risk patients such as those refractory to fludarabine or alkylating agents. In untreated patients with indolent NHL and mantle cell lymphoma, BR has demonstrated a PFS significantly longer than that achieved with R-CHOP (rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone), with significantly reduced toxicity. In the relapsed setting, br has demonstrated rates of response and PFS superior to those with fludarabine-rituximab, with comparable toxicity. In the United States and Europe, bendamustine has been approved for the treatment of CLL and indolent NHL; its approval in Canada is pending and eagerly awaited. Once available, bendamustine will benefit many Canadian patients with NHL and CLL. PMID- 22670097 TI - Recently published indicators allow for comparison of radiation treatment rates relative to evidence-based guidelines for rectal cancer. PMID- 22670096 TI - Eastern Canadian colorectal cancer consensus conference: application of new modalities of staging and treatment of gastrointestinal cancers. AB - The annual Eastern Canadian Colorectal Cancer Consensus Conference was held in Ottawa, Ontario, October 22-23, 2010. Health care professionals involved in the care of patients with colorectal cancer participated in presentation and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses current issues in the management of colorectal cancer, such as the use of epidermal growth factor inhibitors in metastatic colon cancer, the benefit of calcium and magnesium with oxaliplatin chemotherapy, the role of microsatellites in treatment decisions for stage II colon cancer, the staging and treatment of rectal cancer, and the management of colorectal and metastatic pancreatic cancers. PMID- 22670098 TI - Choices for young women at intermediate risk of breast cancer. PMID- 22670099 TI - Humps and bumps: feel them ... like it or lump it. PMID- 22670100 TI - Fitness to drive in patients with brain tumours: the influence of mandatory reporting legislation on radiation oncologists in Canada. AB - BACKGROUND: Certain jurisdictions in Canada legally require that physicians report unfit drivers. Physician attitudes and patterns of practice have yet to be evaluated in Canada for patients with brain tumours. METHODS: We conducted a survey of 97 radiation oncologists, eliciting demographics, knowledge of reporting laws, and attitudes on reporting guidelines for unfit drivers. Eight scenarios with varying disability levels were presented to determine the likelihood of a patient being reported as unfit to drive. Statistical comparisons were made using the Fisher exact test. RESULTS: Of physicians approached, 99% responded, and 97 physicians participated. Most respondents (87%) felt that laws in their province governing the reporting of medically unfit drivers were unclear. Of the responding physicians, 23 (24%) were unable to correctly identify whether their province had mandatory reporting legislation. Physicians from provinces without mandatory reporting legislation were significantly less likely to consider reporting patients to provincial authorities (p = 0.001), and for all clinical scenarios, the likelihood of reporting significantly depended on the physician's provincial legal obligations. CONCLUSIONS: The presence of provincial legislation is of primary importance in determining whether physicians will report brain tumour patients to drivers' licensing authorities. In Canada, clear guidelines have to be developed to help in the assessment of whether brain tumour patients should drive. PMID- 22670101 TI - Specialists' perceptions of hereditary colorectal cancer screening in Newfoundland and Labrador. AB - PURPOSE: Colorectal cancer (CRC) screening is particularly valuable in Newfoundland and Labrador (NL), where a substantial proportion of CRC cases have a hereditary link. We examined the perceptions of gastroenterologists and general surgeons with respect to screening practices for patients with hereditary crc. METHODS: We surveyed all gastroenterologists and general surgeons in NL to determine demographic and professional practice characteristics and screening knowledge, practices, and attitudes for four groups of patients with hereditary CRC. RESULTS: Of the 43 eligible physicians, 36 (83.7%) responded. Most of the physicians surveyed knew the correct age to start screening, preferred screening by colonoscopy, had a systematic means in their own practice of prioritizing patients for screening, and felt that family doctors or patients (or both) should be responsible for monitoring screening compliance. Most physicians reported that patients with hereditary nonpolyposis CRC and familial adenomatous polyposis waited 3 months for screening; patients with a family history of CRC or adenomatous polyp waited 6 months or longer. Although respondents agreed on the need for a province-wide CRC registry [4.36 on a 5-point Likert scale (1 = strongly disagree; 5 = strongly agree)], they disagreed that wait times were reasonable (2.81) and that other health professionals should perform colonoscopies (2.86). They were equivocal about the need for centralized bookings (3.25) and about whether genetic testing is useful for prioritizing patients (3.25). CONCLUSIONS: Gastroenterologists and general surgeons in NL were knowledgeable about screening, but had varying opinions about individual roles in screening, wait times, and the means for prioritizing and providing screening for patients with hereditary CRC. PMID- 22670102 TI - Effect of exercise in reducing breast and chest-wall pain in patients with breast cancer: a pilot study. AB - BACKGROUND: Breast or chest-wall pain (BCP) is prevalent in 20%-50% of breast cancer survivors, and it affects quality of life (QOL). To determine the feasibility and potential efficacy of an exercise program to improve patient QOL and BCP, such a program was offered to breast cancer patients suffering from BCP. METHODS: The study enrolled 10 breast cancer patients with moderate-to-severe BCP at 3-6 months after completion of all adjuvant treatments. These patients participated in a 12-week comprehensive health improvement program (CHIP). Intensity was adjusted to reach 65%-85% of the patient's maximal heart rate. Before the CHIP and at 1 and 6 months after completion of the CHIP, QOL and pain were measured using questionnaires [European Organisation for Research and Treatment of Cancer Quality of Life core and breast cancer modules (QLQ-C30, BR23) and the McGill Pain Questionnaire short form] completed by the patients. Results were compared with those from case-matched control subjects from another study at McGill University. RESULTS: After the CHIP, patients reported significant and clinically important improvements in QOL and symptoms. At 1 and 6 months post-CHIP, patients in the study felt, on average, better in overall QOL than did historical control subjects. CONCLUSIONS: Our study suggests that patients who experience chronic bcp may benefit from an exercise program. A randomized controlled trial is warranted. PMID- 22670105 TI - Outcomes of surveillance for contralateral breast cancer in patients less than age 60 at the time of initial diagnosis. AB - BACKGROUND: After an initial diagnosis of breast cancer, the risk of contralateral breast cancer is approximately 0.5% per year. Annual mammography is recommended to identify local recurrences and contralateral new primaries. Because the sensitivity of mammography tends to be lower in younger women, we conducted a retrospective review of the method of detection and pathologic stage of metachronous contralateral primary breast cancers according to age at diagnosis in a cohort of breast cancer patients. METHODS: The Henrietta Banting Database contains information on cases of breast cancer diagnosed at Women's College Hospital from 1987 to 2004. From among 1992 women in the database, 71 patients were identified who were initially diagnosed before age 60 and who subsequently developed a contralateral breast cancer. Medical records were obtained for 53 of the 71 patients. RESULTS: Of the 53 contralateral cancers, 33 (62%) were detected by mammography, including 4 in 16 patients (25%) diagnosed before age 50 and 29 in 37 patients (78%) diagnosed at age 50 or older (p <= 0.001). CONCLUSIONS: Mammography has poor sensitivity for the surveillance of contralateral breast cancer in early-onset breast cancer patients. Other imaging modalities should be evaluated in this setting. PMID- 22670103 TI - Exercise in clinical cancer care: a call to action and program development description. AB - A large and convincing body of evidence demonstrates the benefits of exercise for cancer survivors during and after treatment. Based on that literature, more cancer survivors should be offered exercise support and programming. Unfortunately, exercise programs remain an exception rather than the norm in cancer care. Not surprisingly, common barriers to the implementation of exercise programs in oncology include limited resources, expertise, and awareness of benefits on the part of patients and clinicians. To improve the accessibility and cost-effectiveness of cancer exercise programs, one proposed strategy is to combine the resources of hospital and community-based programs with home-based exercise instruction. The present paper highlights current literature regarding exercise programming for cancer survivors, describes the development of an exercise program for cancer patients in Toronto, Canada, and offers experiential insights into the integration of exercise into oncologic care. PMID- 22670104 TI - The Peter Brojde lung cancer centre: a model of integrative practice. AB - BACKGROUND: The generally poor prognosis and poor quality of life for lung cancer patients have highlighted the need for a conceptual model of integrative practice. Although the philosophy of integrative oncology is well described, conceptual models that could guide the implementation and scientific evaluation of integrative practice are lacking. PURPOSE: The present paper describes a conceptual model of integrative practice in which the philosophical underpinnings derive mainly from integrative oncology, with important contributions from Traditional Chinese Medicine (TCM) and the discipline of nursing. The conceptual model is described in terms of its purpose, values, concepts, dynamic components, scientific evidence, clinical approach, and theoretical underpinnings. The model argues that these components delineate the initial scope and orientation of integrative practice. They serve as the needed context for evaluating and interpreting the effectiveness of clinical interventions in enhancing patient outcomes in lung cancer at various phases of the illness. Furthermore, the development of relevant and effective integrative clinical interventions requires new research methods based on whole-systems research. An initial focus would be the identification of interrelationship patterns among variables that influence clinical interventions and their targeted patient outcomes. PMID- 22670106 TI - International variability in the reimbursement of cancer drugs by publically funded drug programs. AB - PURPOSE: Evaluate inter-country variability in the reimbursement of publically funded cancer drugs, and identify factors such as cost containment measures that may contribute to variability. METHODS: As of February 28, 2010, licensed indications for 10 cancer drugs (bevacizumab, bortezomib, cetuximab, erlotinib, imatinib, pemetrexed, rituximab, sorafenib, sunitinib, and trastuzumab) were obtained from the drug registries of 6 licensing authorities corresponding to 13 countries or regions: Australia, Canada (Ontario), England, Finland, France, Italy, Germany, Japan, New Zealand, the Netherlands, Scotland, Sweden, and the United States (Medicare Parts B and D). Number of licensed indications reimbursed by public payers and the use of cost containment measures were obtained by survey of health authorities involved in reimbursement and through public documents. RESULTS: The 48 identified licensed indications varied between agencies (range: 36-44 indications). Finland, France, Germany, Sweden, and the United States reimbursed the highest percentage of indications (range: 90%-100%). Canada (54%), Australia (46%), Scotland (40%), England (38%), and New Zealand (25%) reimbursed the least. All 5 countries with the lowest rate of reimbursement incorporated a cost-effectiveness analysis into reimbursement decisions and rejected submissions for reimbursement mainly because of lack of cost effectiveness; in New Zealand, lack of cost effectiveness was the second leading cause of rejection after excessive cost. In 9 countries, risk-sharing agreements were used to contain costs. Indications initially not recommended for reimbursement (9 in Australia, 5 in Canada, and 3 in England, New Zealand, and Scotland) were subsequently approved with risk-sharing agreements or special pricing arrangements. CONCLUSIONS: Reimbursement of publically funded cancer drugs varies globally. The cause is multifactorial. PMID- 22670107 TI - Lymphoepithelioma-like carcinoma of the breast: a diagnostic and therapeutic challenge. AB - We present a patient with lymphoepithelioma-like carcinoma (LELC) of the breast whose diagnosis is illustrative of the pathology nuances that must be taken into account to successfully reach correct identification of the disease. We also present an overview of our patient's proposed treatment in the context of 16 other reported LELC cases. Although LELC cases are rare, a sufficient number have been reported to discern the natural history of this pathologic entity and to undertake a review of those cases and of the application of oncologic first principles in their management. Given the potential for locoregional spread and distant metastases in LELC, adjuvant therapy has a role in the treatment of this entity. PMID- 22670108 TI - Comparison of international breast cancer guidelines: are we globally consistent? cancer guideline AGREEment. AB - BACKGROUND: Evidence-based guidelines are used in health care systems throughout the world to aid in treatment decisions and to ensure quality and consistency in patient care. In breast oncology, guidelines for care are published by several internationally recognized organizations, including those from the United States, Canada, and the United Kingdom. The present study compared clinical breast cancer guidelines from the American Society of Clinical Oncology (ASCO, United States), Cancer Care Ontario (CCO, Canada), and the National Institute for Health and Clinical Excellence (NICE, United Kingdom) to determine the quality and consistency of content across international organizations. METHODS: We searched for breast cancer guidelines published by ASCO, CCO, and NICE. Guidelines on the same theme were identified across organizations and appraised by 4 independent reviewers using the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument. Content of each guideline was also scored for consistency in overall recommendations across organizations and for consistency in cited evidence. RESULTS: The quality of breast cancer guidelines produced by the targeted organizations was consistently good in the areas of Scope and Purpose, Rigor of Development, and Clarity and Presentation, but variable in the domains of Stakeholder Involvement, Applicability, and Editorial Independence. The content of the guidelines varied slightly in the strength of their recommendations. CONCLUSIONS: Our review demonstrated consistency in quality and content for breast cancer practice guidelines published by various organizations. Future guidelines developed by these organizations should focus on how to implement and measure uptake of a guideline. PMID- 22670109 TI - Moderators of psychological recovery from benign cancer screening results. AB - OBJECTIVE: The sudden confrontation of a potential health threat such as cancer, even after the diagnosis turns out to be benign, can have enduring adverse psychological consequences, including persistent anxiety, cancer fears, and other manifestations of psychological distress. The present study examines factors that potentially moderate psychological recovery among women who face a breast cancer threat. DESIGN: Participants were adult women had just received a benign outcome from a breast cancer diagnostic procedure that had been conducted because of suspicion of breast cancer (a non-conclusive mammography or ultrasonography result, a referral from their doctor because of pain or family history, detection of a lump, a 6-month follow-up appointment after a breast abnormality from a previous screening or diagnostic procedure, or a fluid leak from one or both breasts). We measured several psychological traits at Time 1 (right after receipt of the "no cancer" feedback) and then each month for the next 3 months. Analyses examined the factors that hindered or facilitated psychological recovery from the cancer threat. RESULTS: Results showed that trait anxiety and family history of cancer hindered recovery and that older age and optimism facilitated recovery and lessened adverse psychological consequences. Self-regulatory strategies such as planful problem-solving, positive reappraisal, and mastery facilitated recovery. CONCLUSIONS: Our findings shed light on the factors that are implicated in psychological recovery from a benign breast cancer outcome after a diagnostic procedure (ultrasonography, repeat or initial mammography, stereotactic biopsy, fine-needle aspiration, or ultrasound-guided biopsy). Those factors could be used to identify women who may experience prolonged psychological distress, so as to assist them when they face stressful diagnostic concerns. PMID- 22670110 TI - Quality-of-life outcomes in high-risk prostate cancer patients treated with helical tomotherapy in a hypofractionated radiation schedule with long-term androgen suppression. AB - PURPOSE: We examined the impact of hypofractionated radiation therapy and androgen suppression therapy (AST) on quality of life (QOL) in high-risk prostate cancer patients. METHODS: Between March 2005 and March 2007, 60 patients with high-risk prostate cancer were enrolled in a prospective phase ii study. All patients received 68 Gy (2.72 Gy per fraction) to the prostate gland and 45 Gy (1.8 Gy per fraction) to the pelvic lymph nodes in 25 fractions over 5 weeks. Of the 60 patients, 58 received ast. The University of California-Los Angeles Prostate Cancer Index questionnaire was used to prospectively measure QOL at baseline (month 0) and at 1, 6, 12, 18, 24, 30, and 36 months after radiation treatment. The generalized estimating equation approach was used to compare the QOL scores at 1, 6, 12, 18, 24, 30, and 36 months with those at baseline. RESULTS: We observed a significant decrease in QOL items related to bowel and sexual function. Several QOL items related to bowel function were significantly adversely affected at both 1 and 6 months, with improvement toward 6 months. Although decreased QOL scores persisted beyond the 6-month mark, they began to re approach baseline at the 18- to 24-month mark. Most sexual function items were significantly adversely affected at both 1 and 6 months, but the effects were not considered to be a problem by most patients. A complete return to baseline was not observed for either bowel or sexual function. Urinary function items remained largely unaffected, with overall urinary function being the only item adversely affected at 6 months, but not at 1 month. Urinary function returned to baseline and remained unimpaired from 18 months onwards. CONCLUSIONS: In our study population, who received hypofractionated radiation delivered using dynamic intensity-modulated radiotherapy with inclusion of the pelvic lymph nodes, and 2 3 years of ast prescription, QOL with respect to bowel and sexual function was significantly affected; QOL with respect to urinary function was largely unaffected. Our results are comparable to those in other published studies. PMID- 22670111 TI - Caught in the middle: case study of a brachial (sentry) lymph node recurrence after resection and locoregional breast radiotherapy. AB - To reduce local recurrence, adjuvant locoregional radiotherapy is given routinely for post-mastectomy breast patients with 4 or more positive lymph nodes. Most institutions adopt a 3- or 4-field radiotherapy technique, in which the field and shielding placements are informed by bony anatomic landmarks viewed on digitally reconstructed radiographs.Here, we report on a 40-year-old woman who underwent a lumpectomy with axillary node dissection, followed by chemotherapy, completion mastectomy, and adjuvant locoregional radiotherapy (50 Gy in 25 fractions) for a multicentric pT1cN2aM0 invasive ductal carcinoma of the right breast. At 9 months after radiotherapy, she presented with a palpable brachial lymph node, a major draining node of the upper extremity, in the axilla, abutting the previous anterior supraclavicular and axillary radiation fields. This occurrence highlights the potential superolateral border of the level i axillary nodal chain and its relationship to the upper extremity lymphatics via the brachial ("sentry") node. Adapting the delineated nodal target volume in locoregional radiotherapy of the breast for disease with extensive nodal involvement or other high-risk pathologic indications may be warranted in certain situations. Careful imaging and an informed discussion with the patient is needed before deciding to treat the sentry node and including the acromial-clavicular joints, balanced with the potential increased risk of lymphedema. PMID- 22670112 TI - Incidence of febrile neutropenia during adjuvant chemotherapy for breast cancer: a prospective study. PMID- 22670113 TI - Solitary fibrous tumour presenting as a pedunculated lung mass with associated lung atresia: report of a case. AB - This case report describes a solitary fibrous tumour presenting as a pedunculated mass arising from an almost completely atretic right middle lobe of lung. The intraoperative findings and pathologic diagnostic criteria used are described. To our knowledge, this is the first case report of a solitary fibrous tumour associated with partial lung atresia. PMID- 22670114 TI - Neoadjuvant erlotinib and surgical resection of a stage iiia papillary adenocarcinoma of the lung with an L861Q activating EGFR mutation. AB - The use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) is evolving, as is an understanding of predictive biomarkers for tumour response in non-small-cell lung cancer (NSCLC). In this report, we describe a case of rapidly progressing, borderline-resectable, clinical stage IIIA (micro) papillary adenocarcinoma in a 78-year-old woman who experienced a profound response to neoadjuvant erlotinib without short-term toxicity. On EGFR mutation testing, this patient had an uncommon activating point mutation at L861Q in exon 21. Her response permitted successful surgical resection with negative margins and avoidance of chemoradiation, which she was deemed too frail to tolerate. Our case addresses unique management issues such as preoperative testing for EGFR mutation, utility of histology in predicting EGFR mutations, and use of EGFR-TKIs pre- and postoperatively for potentially resectable NSCLC. PMID- 22670117 TI - FOXP3 Expression in GARP-Transduced Helper T Cells Is Not Associated with FOXP3 TSDR Demethylation. AB - AIM: Glycoprotein A repetitions predominant (GARP or LRRC32) represents a human regulatory CD4+ CD25(hi) FOXP3+ T (T(reg)) cell-specific receptor that controls FOXP3. Ectopic expression of GARP in helper T (T(h)) cells has been shown to be sufficient for the induction of FOXP3 and generation of a stable regulatory phenotype. Since expression of FOXP3 in Treg cells is epigenetically controlled by a conserved motif, the so-called T(reg)-specific demethylated region (TSDR), we asked whether GARP-mediated upregulation of FOXP3 in Th cells is similarly accompanied by demethylation of the TSDR. METHODS: DNA methylation of the FOXP3 TSDR was analyzed by direct sequencing of polymerase chain reaction (PCR) products from bisulfite-treated genomic DNA. RESULTS: Although GARP-transduced T(h) cells exhibit constitutive FOXP3 expression and a regulatory phenotype, the FOXP3 TSDR is completely methylated as in naive T(h) cells. GARP-mediated FOXP3 upregulation in T(h) cells is not associated with T(reg)-specific demethylation of the FOXP3 TSDR. CONCLUSION: Although GARP-engineered T(h) cells exhibit stable FOXP3 expression and a phenotypic reprogramming towards T(reg) cells in vitro, these cells do not completely mimic the epigenotype of natural T(reg) cells. Thus, concepts based on the genetic modification of T(h) cells as cellular therapies to treat autoimmune diseases or to control transplantation tolerance should be critically tested before any clinical application. PMID- 22670118 TI - The Austrian Bone Marrow Donor Registry: Providing Patients in Austria with Unrelated Donors for Transplant - a Worldwide Cooperation. AB - BACKGROUND: The Austrian Bone Marrow Donor Registry is the central search coordinating unit in charge of national and international donor searches in Austria. PATIENTS AND METHODS: Between 1988 and 2010, a worldwide search for an unrelated donor of blood stem cells (URD) was initiated for 2,166 Austrian patients with haematological disorders, 1,671 adults and 495 children, by the Austrian Bone Marrow Donor Registry. RESULTS: An URD was identified for 78.3% of the patients between 2008 and 2010, for 76.7% of the patients between 2004 and 2007, for 71.3% between 1996 and 2003, but only for 53.4% of the patients in the initial period of 1988-1995. Thus, results of international donor searches improve over time. In contrast, search duration decreases steadily: Search times of successful searches decreased from about 8 months in the first period between 1988 and 1996 to 1.84 months in 2010. Overall, 1,558 of the 2,166 patients (71.9%) could be provided with a matching donor. However, not every patient provided with a URD was transplanted. Overall, only 1,141 of 2,166 patients (52.7%) proceeded to transplant. CONCLUSION: Figures have significantly improved for the latest period of donor searches between 2008 and 2010. In this period, a donor could be found for 78.3%, and 58.5% of the patients received a transplant. PMID- 22670119 TI - Swiss Blood Stem Cells: More than Just a Registry. AB - Swiss Transfusion SRC, division Swiss Blood Stem Cells (SBSC), is an important national organization for all matters relating to blood stem cells. Not only has its name changed several times over the years but also its role has developed steadily and today goes beyond registry alone. For example, on order of and in close collaboration with transplant doctors, the organization searches for suitable donors worldwide. Searching for unrelated donors for Swiss patients and organizing the deliveries of the transplant tissues for Swiss and foreign patients are the most time-consuming procedures at SBSC. Additionally, the organization pays special attention to the problem of donor follow-up. Here it has made important contributions to the field of data collection (minimal data set) and helped to strengthen international coordination. As of January 2011, the organization has a new structure, because it has joined forces with the SRC Blood Transfusion Service. The new organization will be called Swiss Transfusion SRC, but SBSC remains as a main operational unit of the new organization. In 2009, SBSC implemented a successful new strategy to increase the numbers of donors: donors can now register online. This step led to a remarkable increase of donor numbers from 2009 to 2010. PMID- 22670121 TI - 'Sterility Testing of Blood Components and Advanced Therapy Medicinal Products' (Munich, April 29, 2010) Organized by the DGTI Section 'Safety in Hemotherapy' - Meeting Report. AB - Neither screening method completely detects all clinically relevant bacterial contaminations. The effect of sampling time and volume as well as standardization of the assay applied has also to be taken into account. Therefore, minimizing the risk of contamination during manufacture by measures such as donor selection, skin disinfection, division, and processing within closed systems remains crucial. In this context new concepts in sterility testing, especially with instable advanced therapy medicinal products (ATMPs), are needed as well as reassessment of pathogen inactivation techniques. At present hemovigilance data indicate that shortening the shelf life of platelet concentrates as introduced in Germany 2008 reduced the risk of transfusion-transmitted bacterial infections to the same extent as bacterial screening as done in Canada or the Netherlands. The evolving methodological progress, e.g. by standardizing culture methods or enhancing detection systems, requires careful follow-up in parallel to hemovigilance data in order to ensure optimal bacterial safety in hemotherapy. PMID- 22670120 TI - What Next? The Next Transit from Biology to Diagnostics: Next Generation Sequencing for Immunogenetics. AB - The human genome project triggered the introduction of next generation sequencing (NGS) systems. Although originally developed for total genome sequencing, metagenomics and plant genetics, the ultra-deep sequencing feature of NGS was utilized for diagnostic purposes in HIV resistance and tropism as well in detecting new mutations and tumor clones in oncology. Recent publications exploited the feature of clonal sequencing for immunogenetics to dissolve the growing number of ambiguities. This concept is quite reliable if all exons of interest are tested and the amplification region includes flanking introns. Challenging questions on quality control, cost effectiveness, workflow, and management of enormous loads of data remain if NGS is considered as routine method in the immunogenetics laboratory. If solved, NGS has big potential to have a major impact on immunogenetics by way of providing ambiguity-free HLA-typing results faster, but will also have a great influence on how immunogenetics testing and workflows are organized. PMID- 22670122 TI - Patient Blood Management: Clinical Hemotherapy and Hemostasis Management in Perioperative Settings. PMID- 22670123 TI - DRGs in Transfusion Medicine and Hemotherapy in Germany. AB - Patients requiring transfusion medicine and hemotherapy in an inpatient setting are incorporated into the German Diagnosis Related Groups (G-DRG) system in multiple ways. Different DRGs exist in Major Diagnostic Category 16 for patients that have been admitted for the treatment of a condition from the field of transfusion medicine. However, the reimbursement might be not cost covering for many cases, and efforts have to be intensified to find adequate definitions and prices. We believe that this can only be successful if health service research is intensified in this field. For patients requiring hemotherapy and transfusion medicine concomitant to the treatment of an underlying disease such as cancer, multiple systems exist to increase remuneration, among them the Patient Clinical Complexity Level (PCCL) and complex constellations to induce DRG splits. For direct reimbursement of high cost products, additional remuneration fees (Zusatzentgelte, ZE) are the most important. In addition, expensive innovations not reflected within the DRGs can be reimbursed after application and negotiation of the New Diagnostic and Treatment Methods (Neue Untersuchungs-und Behandlungsmethoden, NUB) system. The NUB system guarantees that medical progress is put rapidly into clinical practice and prevents financial issues from becoming a stumbling block for the use of innovative drugs and methods. PMID- 22670124 TI - Patient Blood Management: A Patient-Orientated Approach to Blood Replacement with the Goal of Reducing Anemia, Blood Loss and the Need for Blood Transfusion in Elective Surgery. AB - Patient Blood Management (PBM) describes an evidence-based, multidisciplinary therapeutic approach. Its focus is on the treatment of the individual patient and as such comprises transfusion therapy and pharmacotherapy. Furthermore, the applicability of PBM is not limited to the perioperative setting but is applicable also to other therapeutic measures and disciplines where significant blood loss is known to occur and where transfusion of blood products is part of the established treatment. PBM is fundamentally based on 3 pillars: (1) optimization of the (preoperative) erythrocyte volume, (2) reduction of diagnostic, therapeutic, or intraoperative blood loss, and (3) increasing individual tolerance towards anemia and accurate blood transfusion triggers. PBM primarily identifies patients at risk of transfusion and provides a management plan aimed at reducing or eliminating the risk of anemia and the need for allogeneic transfusion, thus reducing the inherent risks, inventory pressures, and the escalating costs associated with transfusion. PMID- 22670125 TI - Massive Bleeding and Massive Transfusion. AB - Massive bleeding in trauma patients is a serious challenge for all clinicians, and an interdisciplinary diagnostic and therapeutic approach is warranted within a limited time frame. Massive transfusion usually is defined as the transfusion of more than 10 units of packed red blood cells (RBCs) within 24 h or a corresponding blood loss of more than 1- to 1.5-fold of the body's entire blood volume. Especially male trauma patients experience this life-threatening condition within their productive years of life. An important parameter for clinical outcome is to succeed in stopping the bleeding preferentially within the first 12 h of hospital admission. Additional coagulopathy in the initial phase is induced by trauma itself and aggravated by consumption and dilution of clotting factors. Although different aspects have to be taken into consideration when viewing at bleedings induced by trauma compared to those caused by major surgery, the basic strategy is similar. Here, we will focus on trauma-induced massive hemorrhage. Currently there are no definite, worldwide accepted algorithms for blood transfusion and strategies for optimal coagulation management. There is increasing evidence that a higher ratio of plasma and RBCs (e.g. 1:1) endorsed by platelet transfusion might result in a superior survival of patients at risk for trauma-induced coagulopathy. Several strategies have been evolved in the military environment, although not all strategies should be transferred unproven to civilian practice, e.g. the transfusion of whole blood. Several agents have been proposed to support the restoration of coagulation. Some have been used for years without any doubt on their benefit-to-risk profile, whereas great enthusiasm of other products has been discouraged by inefficacy in terms of blood transfusion requirements and mortality or significant severe side effects. This review surveys current literature on fluid resuscitation, blood transfusion, and hemostatic agents currently used during massive hemorrhage in order to optimize patients' blood and coagulation management in emergency medical aid. PMID- 22670126 TI - Predictive Models and Algorithms for the Need of Transfusion Including Massive Transfusion in Severely Injured Patients. AB - BACKGROUND: Despite improvements on how to resuscitate exsanguinating patients, one remaining key to improve outcome is to expeditiously and reproducibly identify patients most likely to require transfusion including massive transfusion (MT). This work summarizes yet developed algorithms/scoring systems for transfusion including MT in civilian and military trauma populations. METHODS: A systematic search of evidence was conducted utilizing OVID/MEDLINE (1966 to present) and the 'Medical Algorithms Project'. RESULTS AND CONCLUSIONS: The models developed suggest combinations of physiologic, hemodynamic, laboratory, injury severity and demographic triggers identified on the initial evaluation of the bleeding trauma patient. Many approaches use a combination of dichotomous variables readily accessible after arrival but others rely on time consuming calculations or complex algorithms and may have limited real-time application. Weighted and more sophisticated systems including higher numbers of variables perform superior. A common limitation to all models is their retrospective nature, and prospective validations are urgently needed. Point-of care viscoelastic testing may be an alternative to these systems. PMID- 22670127 TI - Perioperative Red Blood Cell Transfusion: Harmful or Beneficial to the Patient? AB - Although the transfusion of red blood cells (RBCs) is safer than ever regarding infections, it is still associated with several adverse reactions and therefore should only be used on the basis of evidence-based triggers. However, prevention of RBC transfusion and subsequent substitution of blood losses with acellular solutions will inevitably result in dilutional anemia. Acute dilutional anemia can be compensated by the body over a wide range of hemoglobin concentrations without a critical restriction of tissue oxygenation. On the other hand, chronic anemia is known to be a potent cause of morbidity and mortality. As a consequence, the impact of perioperative anemia on mortality is difficult to describe, because anemia, as well as the transfusion of RBCs, can influence the clinical outcome. The resulting 'Gordian knot' cannot be cut easily, and this circumstance forces clinical physicians to make a daily trade-off between transfusion-associated and anemia-associated risks. This review focuses on the physiology of oxygen transport, the hazards of acute anemia, the hazards of RBC transfusion, and the literature putting these problems into perspective. PMID- 22670128 TI - Reduction of Fresh Frozen Plasma Requirements by Perioperative Point-of-Care Coagulation Management with Early Calculated Goal-Directed Therapy. AB - BACKGROUND: Massive bleeding and transfusion of packed red blood cells (PRBC), fresh frozen plasma (FFP) and platelets are associated with increased morbidity, mortality and costs. PATIENTS AND METHODS: We analysed the transfusion requirements after implementation of point-of-care (POC) coagulation management algorithms based on early, calculated, goal-directed therapy with fibrinogen concentrate and prothrombin complex concentrate (PCC) in different perioperative settings (trauma surgery, visceral and transplant surgery (VTS), cardiovascular surgery (CVS) and general and surgical intensive care medicine) at 3 different hospitals (AUVA Trauma Centre Salzburg, University Hospital Innsbruck and University Hospital Essen) in 2 different countries (Austria and Germany). RESULTS: In all institutions, the implementation of POC coagulation management algorithms was associated with a reduction in the transfusion requirements for FFP by about 90% (Salzburg 94%, Innsbruck 88% and Essen 93%). Furthermore, PRBC transfusion was reduced by 8.4-62%. The incidence of intraoperative massive transfusion (>=10 U PRBC) could be more than halved in VTS and CVS (2.56 vs. 0.88%; p < 0.0001 and 2.50 vs. 1.06%; p = 0.0007, respectively). Platelet transfusion could be reduced by 21-72%, except in CVS where it increased by 115% due to a 5-fold increase in patients with dual antiplatelet therapy (2.7 vs. 13.7%; p < 0.0001). CONCLUSIONS: The implementation of perioperative POC coagulation management algorithms based on early, calculated, goal-directed therapy with fibrinogen concentrate and PCC is associated with a reduction in the transfusion requirements for FFP, PRBC and platelets as well as with a reduced incidence of massive transfusion. Thus, the limited blood resources can be used more efficiently. PMID- 22670129 TI - Management of Dilutional Coagulopathy during Pediatric Major Surgery. AB - Perioperative dilutional coagulopathy is a major coagulation disorder during adult and pediatric surgery. Although the main underlying mechanisms are comparable, data of the development and management of dilutional coagulopathy in children are scarce. Observational data showed that intraoperative coagulation disorders mainly based on complex disturbances of clot firmness including acquired fibrinogen as well as factor XIII deficiencies, while clotting time and platelet counts remained fairly stable. A fast and reliable monitoring of the entire coagulation process (e.g. thrombelastometry) might be of extreme value for detection and guidance of effective coagulation management. Although the transfusion of fresh frozen plasma was recommended in several guidelines, the use of coagulation factors might offer an alternative and potentially superior approach in managing perioperative coagulation disorders. Further studies are urgently needed to determine the efficacy of modern coagulation management. PMID- 22670130 TI - Thromboelastometry Based Early Goal-Directed Coagulation Management Reduces Blood Transfusion Requirements, Adverse Events, and Costs in Acute Type A Aortic Dissection: A Pilot Study. AB - BACKGROUND: In aortic surgery bleeding complications can be fatal. Therefore, rotational thromboelastometry(ROTEMTM)-based coagulation management was introduced. METHODS: After 5 cases of acute type A aortic dissection and aortic arch replacement had been treated based on ROTEM findings (ROTEM group; RG), 5 cases without ROTEM were matched as control group (CG). CG treatment was based on conventional tests and clinical findings. Blood component and coagulation factor requirements, ventilation time, duration of stay at intensive care unit (ICU), hospitalization, and thrombotic or bleeding incidents as well as transfusion associated costs were compared. RESULTS: Administration of blood products and coagulation factor concentrates, ventilation time, ICU length of stay, and hospitalization tended to be lower in RG. Postoperative plasma transfusion (p = 0.038), recognized incidents (p = 0.048), and resulting costs on coagulation treatment (p = 0.049) were significantly reduced. CONCLUSION: Our data suggest that ROTEM-based coagulation management can reduce transfusion requirements and corresponding costs in patients with aortic arch replacement. These data has to be confirmed by prospective randomized trials. PMID- 22670131 TI - Retrospective Analysis of the Blood Component Utilization in a University Hospital of Maximum Medical Care. AB - BACKGROUND: Demographic data illustrate clearly that people in highly developed countries get older, and the elderly need more blood transfusions than younger patients. Additionally, special extensive therapies result in an increased consumption of blood components. Beyond that the aging of the population reduces the total number of preferably young and healthy blood donors. Therefore, Patient Blood Management will become more and more important in order to secure an increasing blood supply under fair-minded conditions. METHODS: At the University Hospital of Munster (UKM) a comprehensive retrospective analysis of the utilization of all conventional blood components was performed including all medical and surgical disciplines. In parallel, a new medical reporting system was installed to provide a monthly analysis of the transfusional treatments in the whole infirmary, in every department, and in special blood-consuming cases of interest, as well. RESULTS: The study refers to all UKM in-patient cases from 2009 to 2011. It clearly demonstrates that older patients (>60 years, 35.2-35.7% of all cases, but 49.4-52.6% of all cases with red blood cell (RBC) transfusions, 36.4-41. 6% of all cases with platelet (PTL, apheresis only) transfusions, 45.2 48.0% of all cases with fresh frozen plasma (FFP) transfusions) need more blood products than younger patients. Male patients (54.4-63.9% of all cases with transfusions) are more susceptible to blood transfusions than female patients (36.1-45.6% of all cases with transfusions). Most blood components are used in cardiac, visceral, and orthopedic surgery (49.3-55.9% of all RBC units, 45.8 61.0% of all FFP units). When regarding medical disciplines, most transfusions are administered to hematologic and oncologic patients (12.9-17.7% of all RBC units, 9.2-12.0% of all FFP units). The consumption of PTL in this special patient cohort (40.6-50.9% of all PTL units) is more pronounced than in all other surgical or in non-surgical disciplines. CONCLUSION: The results obtained from our retrospective analysis may help to further optimize the responsible and medical indication-related utilization of blood transfusions as well as the recruitment of blood donors and their timing. It may be also a helpful tool in order to avoid needless transfusions and transfusionassociated adverse events. PMID- 22670132 TI - Use of Activated Recombinant Factor VII in Severe Bleeding - Evidence for Efficacy and Safety in Trauma, Postpartum Hemorrhage, Cardiac Surgery, and Gastrointestinal Bleeding. AB - BACKGROUND: Uncontrolled bleeding continues to be a major cause of mortality in trauma, cardiac surgery, postpartum hemorrhage and liver failure. The aim of this paper is to assess the evidence supporting the efficacy of activated recombinant factor VII (rFVIIa) administration in these settings. METHODS: Electronic literature search. RESULTS: Numerous retrospective trials have mostly shown a decrease in blood transfusion requirements with no increase in thromboembolic events (TEE), but major limitations in trial design make generalization difficult. In most retrospective reports rFVIIa has been administered as a last ditch attempt to control bleeding, when acidosis, hypothermia and coagulation factor depletion may not allow optimal rFVIIa effect. Prospective randomized controlled trials have not shown any effect of rFVIIa on mortality or TEE, although some have shown a reduction in RBC requirement. CONCLUSION: Stipulated transfusion protocols in prospective trials have reduced anticipated mortality among controls and make future trials for mortality effect unlikely in view of large sample size requirements. Establishment of these protocols and rapid hemostasis are likely to have greater benefits than administration of a single agent. PMID- 22670133 TI - Molecular and Clinical Aspects of Angelman Syndrome. AB - The Angelman syndrome is caused by disruption of the UBE3A gene and is clinically delineated by the combination of severe mental disability, seizures, absent speech, hypermotoric and ataxic movements, and certain remarkable behaviors. Those with the syndrome have a predisposition toward apparent happiness and paroxysms of laughter, and this finding helps distinguish Angelman syndrome from other conditions involving severe developmental handicap. Accurate diagnosis rests on a combination of clinical criteria and molecular and/or cytogenetic testing. Analysis of parent-specific DNA methylation imprints in the critical 15q11.2-q13 genomic region identifies 75-80% of all individuals with the syndrome, including those with cytogenetic deletions, imprinting center defects and paternal uniparental disomy. In the remaining group, UBE3A sequence analysis identifies an additional percentage of patients, but 5-10% will remain who appear to have the major clinical phenotypic features but do not have any identifiable genetic abnormalities. Genetic counseling for recurrence risk is complicated because multiple genetic mechanisms can disrupt the UBE3A gene, and there is also a unique inheritance pattern associated with UBE3A imprinting. Angelman syndrome is a prototypical developmental syndrome due to its remarkable behavioral phenotype and because UBE3A is so crucial to normal synaptic function and neural plasticity. PMID- 22670134 TI - Rett Syndrome. AB - Rett syndrome is one of the most common causes of complex disability in girls. It is characterized by early neurological regression that severely affects motor, cognitive and communication skills, by autonomic dysfunction and often a seizure disorder. It is a monogenic X-linked dominant neurodevelopmental disorder related to mutation in MECP2, which encodes the methyl-CpG-binding protein MeCP2. There are several mouse models either based on conditional knocking out of the Mecp2 gene or on a truncating mutation. We discuss the clinical aspects with special emphasis on the behavioral phenotype and we review current perspectives in clinical management alongside with perspectives in altering gene expression. PMID- 22670135 TI - CDKL5-Related Disorders: From Clinical Description to Molecular Genetics. AB - Mutations in the cyclin-dependent kinase-like 5 gene (CDKL5) have been described in girls with Rett-like features and early-onset epileptic encephalopathy including infantile spasms. To date, with more than 80 reported cases, the phenotype of CDKL5-related encephalopathy is better defined. The main features consist of early-onset seizures starting before 5 months of age, severe mental retardation with absent speech and Rett-like features such as hand stereotypies and deceleration of head growth. On the other hand, neuro-vegetative signs and developmental regression are rare in CDKL5 mutation patients. The CDKL5 gene encodes a serine threonine kinase protein which is characterized by a catalytic domain and a long C-terminal extension involved in the regulation of the catalytic activity of CDKL5 and in the sub-nuclear localization of the protein. To our knowledge, more than 70 different point mutations have been described including missense mutations within the catalytic domain, nonsense mutations causing the premature termination of the protein distributed in the entire open reading frame, splice variants, and frameshift mutations. Additionally, CDKL5 mutations have recently been described in 7 males with a more severe epileptic encephalopathy and a worse outcome compared to female patients. Finally, about 23 male and female patients have been identified with gross rearrangements encompassing all or part of the CDKL5 gene, with a phenotype reminiscent of CDKL5 related encephalopathy combined with dysmorphic features. Even if recent data clearly indicate that CDKL5 plays an important role in brain function, the protein remains largely uncharacterized. Phenotype-genotype correlation is additionally hampered by the relatively small number of patients described. PMID- 22670136 TI - FOXG1-Related Disorders: From Clinical Description to Molecular Genetics. AB - Rett syndrome (RTT) is a severe neurodevelopmental disease that affects approximately 1 in 10,000 live female births and is often caused by mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MECP2). Mutations in loci other than MECP2 have also been found in individuals that have been labeled as atypical RTT. Among them, a mutation in the gene forkhead box G1 (FOXG1) has been involved in the molecular aetiology of the congenital variant of RTT. The FOXG1 gene encodes a winged-helix transcriptional repressor essential for the development of the ventral telencephalon in embryonic forebrain. Later, FOXG1 continues to be expressed in neurogenetic zones of the postnatal brain. Although RTT affects quasi-exclusively girls, FOXG1 mutations have also been identified in male patients. As far as we know, about 12 point mutations and 13 cases with FOXG1 molecular abnormalities (including translocation, duplication and large deletion on the chromosome 14q12) have been described in the literature. Affected individuals with FOXG1 mutations have shown dysmorphic features and Rett-like clinical course, including normal perinatal period, postnatal microcephaly, seizures and severe mental retardation. Interestingly, the existing animal models of FOXG1 deficiency showed similar phenotype, suggesting that animal models may be a fascinating model to understand this human disease. Here, we describe the impacts of FOXG1 mutations and their associated phenotypes in human and mouse models. PMID- 22670137 TI - The MEF2C-Related and 5q14.3q15 Microdeletion Syndrome. AB - Disorders related to the autosomal transcription factor MEF2C located in 5q14.3 were first described in 2009 and have since evolved to one of the more common microdeletion syndromes. Mutational screening in a larger cohort revealed heterozygous de novo mutations of MEF2C in about 1% of patients with moderate to severe intellectual disability, and the phenotype is similar in patients with intragenic deletions and multigenic microdeletions. Clinically, MEF2C-related disorders are characterized by severe intellectual disability with absent speech and limited walking abilities, hypotonia, seizures, and a variety of minor brain anomalies. The majority of patients show a similar facial gestalt with broad forehead, flat nasal bridge, hypotonic mouth, and small chin, as well as strabismus, but this phenotype is clinically not well recognized. The course of the disease is generally quite uniform, but patients with point mutations and smaller deletions seem to have a higher chance of walking skills and a lower risk of refractory seizures. Patients in whom the microdeletion also includes the RASA1 gene show features of the respective capillary and arterio-venous malformations and fistula syndrome. The phenotypic overlap with Rett syndrome is explained by a shared pathway and, accordingly, diminished MECP2 and CDKL5 expression is measureable in patients with MEF2C defects. Further research of this pathway may therefore eventually lead to a common therapeutic target. PMID- 22670138 TI - Pitt-Hopkins Syndrome. AB - Pitt-Hopkins syndrome (PTHS, MIM #610954) is characterized by severe intellectual disability, typical facial features and tendency to epilepsy, panting-and-holding breathing anomaly, stereotypic movements, constipation, and high myopia. Growth is normal or only mildly retarded, but half of the patients have postnatal microcephaly. Remarkably, congenital malformations are practically nonexistent. The cause of PTHS is de novo haploinsufficiency of the TCF4 gene (MIM *602272) at 18q21.2. Altogether 78 PTHS patients with abnormalities of the TCF4 gene have been published since 2007 when the etiology of PTHS was revealed. In addition, 27 patients with 18q deletion encompassing the TCF4 gene but without given PTHS diagnosis have been published, and thus, the number of reported patients with a TCF4 abnormality exceeds 100. The mutational spectrum includes large chromosomal deletions encompassing the whole TCF4 gene, partial gene deletions, frameshift (including premature stop codon), nonsense, splice site, and missense mutations. So far, almost all patients have a private mutation and only 2 recurrent mutations are known. There is no evident genotype-phenotype correlation. No familial cases have been reported. Diagnosis of PTHS is based on the molecular confirmation of the characteristic clinical features. Recently, a Pitt-Hopkins like phenotype has been assigned to autosomal recessive mutations of the CNTNAP2 gene at 7q33q36 and the NRXN1 gene at 2p16.3. PMID- 22670139 TI - Severe Intellectual Disability Associated with Recessive Defects in CNTNAP2 and NRXN1. AB - While heterozygous variants in CNTNAP2 and NRXN1 are reported as susceptibility factors for neuropsychiatric disorders, homozygous or compound heterozygous defects in either gene were reported as causative for severe neurodevelopmental disorders. This review provides an overview of the clinical aspects in patients with recessive defects in CNTNAP2 and NRXN1. PMID- 22670140 TI - The 22q13.3 Deletion Syndrome (Phelan-McDermid Syndrome). AB - The 22q13.3 deletion syndrome, also known as Phelan-McDermid syndrome, is a contiguous gene disorder resulting from deletion of the distal long arm of chromosome 22. In addition to normal growth and a constellation of minor dysmorphic features, this syndrome is characterized by neurological deficits which include global developmental delay, moderate to severe intellectual impairment, absent or severely delayed speech, and neonatal hypotonia. In addition, more than 50% of patients show autism or autistic-like behavior, and therefore it can be classified as a syndromic form of autism spectrum disorders (ASD). The differential diagnosis includes Angelman syndrome, velocardiofacial syndrome, fragile X syndrome, and FG syndrome. Over 600 cases of 22q13.3 deletion syndrome have been documented. Most are terminal deletions of ~100 kb to >9 Mb, resulting from simple deletions, ring chromosomes, and unbalanced translocations. Almost all of these deletions include the gene SHANK3 which encodes a scaffold protein in the postsynaptic densities of excitatory synapses, connecting membrane bound receptors to the actin cytoskeleton. Two mouse knockout models and cell culture experiments show that SHANK3 is involved in the structure and function of synapses and support the hypothesis that the majority of 22q13.3 deletion syndrome neurological defects are due to haploinsufficiency of SHANK3, although other genes in the region may also play a role in the syndrome. The molecular connection to ASD suggests that potential future treatments may involve modulation of metabotropic glutamate receptors. PMID- 22670141 TI - Update on Kleefstra Syndrome. AB - Kleefstra syndrome is characterized by the core phenotype of developmental delay/intellectual disability, (childhood) hypotonia and distinct facial features. The syndrome can be either caused by a microdeletion in chromosomal region 9q34.3 or by a mutation in the euchromatin histone methyltransferase 1 (EHMT1) gene. Since the early 1990s, 85 patients have been described, of which the majority had a 9q34.3 microdeletion (>85%). So far, no clear genotype phenotype correlation could be observed by studying the clinical and molecular features of both 9q34.3 microdeletion patients and patients with an intragenic EHMT1 mutation. Thus, to further expand the genotypic and phenotypic knowledge about the syndrome, we here report 29 newly diagnosed patients, including 16 patients with a 9q34.3 microdeletion and 13 patients with an EHMT1 mutation, and review previous literature. The present findings are comparable to previous reports. In addition to our former findings and recommendations, we suggest cardiac screening during follow-up, because of the possible occurrence of cardiac arrhythmias. In addition, clinicians and caretakers should be aware of the regressive behavioral phenotype that might develop at adolescent/adult age and seems to have no clear neurological substrate, but is rather a so far unexplained neuropsychiatric feature. PMID- 22670142 TI - Mild to Moderate Intellectual Disability and Significant Speech and Language Deficits in Patients with FOXP1 Deletions and Mutations. AB - Very recently, FOXP1 deficiency was shown to result in a phenotype of intellectual disability with significant speech and language impairment. Behavioral abnormalities should be considered as part of the clinical spectrum. Mild craniofacial abnormalities found in half of the described patients expand the clinical spectrum associated with FOXP1 mutations. PMID- 22670144 TI - RE(ACT)(r): INTERNATIONAL CONGRESS ON RESEARCH ON RARE AND ORPHAN DISEASES. PMID- 22670143 TI - Adult Phenotypes in Angelman- and Rett-Like Syndromes. AB - BACKGROUND: Angelman- and Rett-like syndromes share a range of clinical characteristics, including intellectual disability (ID) with or without regression, epilepsy, infantile encephalopathy, postnatal microcephaly, features of autism spectrum disorder, and variable other neurological symptoms. The phenotypic spectrum generally has been well studied in children; however, evolution of the phenotypic spectrum into adulthood has been documented less extensively. To obtain more insight into natural course and prognosis of these syndromes with respect to developmental, medical, and socio-behavioral outcomes, we studied the phenotypes of 9 adult patients who were recently diagnosed with 6 different Angelman- and Rett-like syndromes. METHODS: All these patients were ascertained during an ongoing cohort study involving a systematic clinical genetic diagnostic evaluation of over 250, mainly adult patients with ID of unknown etiology. RESULTS: We describe the evolution of the phenotype in adults with EHMT1, TCF4, MECP2, CDKL5, and SCN1A mutations and 22qter deletions and also provide an overview of previously published adult cases with similar diagnoses. CONCLUSION: These data are highly valuable in adequate management and follow-up of patients with Angelman- and Rett-like syndromes and accurate counseling of their family members. Furthermore, they will contribute to recognition of these syndromes in previously undiagnosed adult patients. PMID- 22670145 TI - New frontiers in the neuroscience of the sense of agency. AB - The sense that I am the author of my own actions, including the ability to distinguish my own from other people's actions, is a fundamental building block of our sense of self, on the one hand, and successful social interactions, on the other. Using cognitive neuroscience techniques, researchers have attempted to elucidate the functional basis of this intriguing phenomenon, also trying to explain pathological abnormalities of action awareness in certain psychiatric and neurological disturbances. Recent conceptual, technological, and methodological advances suggest several interesting and necessary new leads for future research on the neuroscience of agency. Here I will describe new frontiers for the field such as the need for novel and multifactorial paradigms, anatomically plausible network models for the sense of agency, investigations of the temporal dynamics during agentic processing and ecologically valid virtual reality (VR) applications. PMID- 22670146 TI - Wading pools, fading memories-place navigation in transgenic mouse models of Alzheimer's disease. AB - The Morris swim navigation task ("water maze") has been a primary research tool to assess hippocampal-dependent spatial learning and memory in rodents for three decades. Originally developed for rats, its application to mouse studies has been a tedious process, but nowadays there are more studies performed with the Morris swim task in mice than in rats. The task has proved to be particularly useful in demonstrating age-related memory impairment in transgenic mouse models of Alzheimer's disease (AD). This review focuses on task details that are most relevant for its application to mouse studies in general and characteristic patterns of impaired performance in Alzheimer model mice as compared with rodents sustaining hippocampal lesions. PMID- 22670147 TI - L-py: an L-system simulation framework for modeling plant architecture development based on a dynamic language. AB - The study of plant development requires increasingly powerful modeling tools to help understand and simulate the growth and functioning of plants. In the last decade, the formalism of L-systems has emerged as a major paradigm for modeling plant development. Previous implementations of this formalism were made based on static languages, i.e., languages that require explicit definition of variable types before using them. These languages are often efficient but involve quite a lot of syntactic overhead, thus restricting the flexibility of use for modelers. In this work, we present an adaptation of L-systems to the Python language, a popular and powerful open-license dynamic language. We show that the use of dynamic language properties makes it possible to enhance the development of plant growth models: (i) by keeping a simple syntax while allowing for high-level programming constructs, (ii) by making code execution easy and avoiding compilation overhead, (iii) by allowing a high-level of model reusability and the building of complex modular models, and (iv) by providing powerful solutions to integrate MTG data-structures (that are a common way to represent plants at several scales) into L-systems and thus enabling to use a wide spectrum of computer tools based on MTGs developed for plant architecture. We then illustrate the use of L-Py in real applications to build complex models or to teach plant modeling in the classroom. PMID- 22670148 TI - Mutations and binding sites of human transcription factors. AB - Mutations in any genome may lead to phenotype characteristics that determine ability of an individual to cope with adaptation to environmental challenges. In studies of human biology, among the most interesting ones are phenotype characteristics that determine responses to drug treatments, response to infections, or predisposition to specific inherited diseases. Most of the research in this field has been focused on the studies of mutation effects on the final gene products, peptides, and their alterations. Considerably less attention was given to the mutations that may affect regulatory mechanism(s) of gene expression, although these may also affect the phenotype characteristics. In this study we make a pilot analysis of mutations observed in the regulatory regions of 24,667 human RefSeq genes. Our study reveals that out of eight studied mutation types, "insertions" are the only one that in a statistically significant manner alters predicted transcription factor binding sites (TFBSs). We also find that 25 families of TFBSs have been altered by mutations in a statistically significant manner in the promoter regions we considered. Moreover, we find that the related transcription factors are, for example, prominent in processes related to intracellular signaling; cell fate; morphogenesis of organs and epithelium; development of urogenital system, epithelium, and tube; neuron fate commitment. Our study highlights the significance of studying mutations within the genes regulatory regions and opens way for further detailed investigations on this topic, particularly on the downstream affected pathways. PMID- 22670149 TI - Food allergy. AB - Food allergy is an important public health problem affecting 5% of infants and children in Korea. Food allergy is defined as an immune response triggered by food proteins. Food allergy is highly associated with atopic dermatitis and is one of the most common triggers of potentially fatal anaphylaxis in the community. Sensitization to food allergens can occur in the gastrointestinal tract (class 1 food allergy) or as a consequence of cross reactivity to structurally homologous inhalant allergens (class 2 food allergy). Allergenicity of food is largely determined by structural aspects, including cross-reactivity and reduced or enhanced allergenicity with cooking that convey allergenic characteristics to food. Management of food allergy currently focuses on dietary avoidance of the offending foods, prompt recognition and treatment of allergic reactions, and nutritional support. This review includes definitions and examines the prevalence and management of food allergies and the characteristics of food allergens. PMID- 22670150 TI - Cognitive function of idiopathic childhood epilepsy. AB - Most children with epilepsy are of normal intelligence. However, a significant subset will have temporary or permanent cognitive impairment. Factors that affect cognitive function are myriad and include the underlying neuropathology of the epilepsy, seizures, epileptiform discharges, psychosocial problems, age at seizure onset, duration of epilepsy, and side effects associated with antiepileptic drugs. This review article discusses cognitive function in children with idiopathic epilepsy and the effects of antiepileptic drugs on cognitive function in children. PMID- 22670151 TI - Successful and safe treatment of hemangioma with oral propranolol in a single institution. AB - PURPOSE: Dramatic improvement of hemangioma to propranolol has been recently reported; however, details on dose and duration of treatment, potential risks, and monitoring have not been determined. The objective of this study is to describe and analyze the use of propranolol as a first-line treatment or as a single therapy in management of complicated hemangioma. METHODS: A retrospective chart review of eight patients diagnosed with hemangioma and treated with propranolol in Kangbuk Samsung Hospital from February 2010 to April 2011 was performed. RESULTS: Eight patients with hemangioma with functional impairment, cosmetic disfigurement, or rapid growth were treated with propranolol. Five patients had solitary facial hemangioma. The mean age of symptoms at onset was 5 weeks. The median age for starting propranolol treatment was 5.5 months. Propranolol at 2 mg/kg/day was finally administered in divided doses with a gradual increase. Significant regression was observed in seven patients, and shrinkage in size, softening in consistency, and decrease in redness were evident within 4 weeks. Among them, six patients were still taking propranolol, and one patient had stopped after 12 months. Other one patient did not show significant improvement with satisfactory result after 3 months of propranolol use. Treatment with propranolol was well tolerated and had few side effects. No rebound growth was observed in any of the patients. CONCLUSION: We observed that use of propranolol was very effective in treatment of hemangioma without obvious adverse effects or relapse. PMID- 22670152 TI - Epilepsy in Korean patients with Angelman syndrome. AB - PURPOSE: The aim of this study was to investigate the natural history of epilepsy and response to anti-epileptic drug treatment in patients with Angelman syndrome (AS) in Korea. METHODS: We retrospectively reviewed the clinical records of 14 patients diagnosed with epilepsy out of a total of 17 patients with a genetic diagnosis of AS. These patients were seen at the Department of Pediatric Neurology at Severance Children's Hospital from March 2005 to March 2011. RESULTS: Fourteen (9 males and 5 females) subjects (82.3%) were diagnosed with epilepsy in AS. The most common seizure types were generalized tonic-clonic (n=9, 27%) and myoclonic (n=9, 27%), followed by atonic (n=8, 24%), atypical absence (n=4, 12%) and complex partial seizure (n=3, 9%). The most commonly prescribed antiepileptic drug (AED) was valproic acid (VPA, n=12, 86%), followed by lamotrigine (LTG, n=9, 64%), and topiramate (n=8, 57%). According to questionnaires that determined whether each AED was efficacious or not, VPA had the highest response rate and LTG was associated with the highest rate of seizure exacerbation. Complete control of seizures was achieved in 6 patients. Partial control was achieved in 7 patients, while one patient was not controlled. CONCLUSION: Epilepsy is observed in the great majority of AS patients. It may have early onset and is often refractory to treatment. There are few reports about epilepsy in AS in Korea. This study will be helpful in understanding epilepsy in AS in Korea. PMID- 22670153 TI - Successful pleurodesis with OK-432 in preterm infants with persistent pleural effusion. AB - OK-432 (picibanil) is an inactivated preparation of Streptococcus pyogenes that causes pleurodesis by inducing a strong inflammatory response. Intrapleural instillation of OK-432 has recently been used to successfully treat neonatal and fetal chylothorax. Here we report a trial of intrapleural instillation of OK-432 in two preterm infants who were born with hydrops fetalis and massive bilateral pleural effusion. Both cases showed persistent pleural effusion, refractory to conservative treatment, up to postnatal days 26 and 46, respectively. An average of 80 to 140 mL of pleural fluid was drained daily. In case 1, the infant was treated with OK-432 during the fetal period at gestation 28 weeks and 4 days of gestation, but showed recurrence of pleural effusion and progressed into hydrops. Within two to three days after OK-432 injection, the amount of pleural fluid drainage was dramatically decreased and there was no reaccumulation. We did not observe any side effects related to OK-432 injection. We suggest that OK-432 should be considered as a therapeutic option in infants who have persistent pleural effusion for more than four weeks, with the expectation of the early removal of the chest tube and a good outcome. PMID- 22670154 TI - Urinary bladder rupture during voiding cystourethrography. AB - Voiding cystourethrography (VCUG) is a commonly performed diagnostic procedure for the evaluation of vesicoureteral reflux with urinary tract infection or congenital renal diseases in children. The procedure is relatively simple and cost-effective, and complications are very rare. The iatrogenic complication of VCUG range from discomfort, urinary tract infection to bacteremia, as well as bladder rupture. Bladder rupture is a rare complication of VCUG, and only a few cases were reported. Bladder rupture among healthy children during VCUG is an especially uncommon event. Bladder rupture associated with VCUG is usually more common in chronically unused bladders like chronic renal failure. Presented is a case of bladder rupture that occurred during a VCUG in a healthy 9-month-old infant, due to instilled action of dye by high pressure. This injury completely healed after 7 days of operation, and it was confirmed with a postoperative cystography. The patient's bladder volume, underlying disease, velocity of the contrast media instilled, catheter size, and styles of instillation are important factors to prevent bladder rupture during VCUG. Management of bladder rupture should be individualized, but the majority of infants are treated with the operation. In conclusion, bladder rupture is a rare complication, however, delicate attention is needed in order to prevent more dire situations. PMID- 22670155 TI - An Adaptive Mesh Refinement Strategy for Immersed Boundary/Interface Methods. AB - An adaptive mesh refinement strategy is proposed in this paper for the Immersed Boundary and Immersed Interface methods for two-dimensional elliptic interface problems involving singular sources. The interface is represented by the zero level set of a Lipschitz function phi(x,y). Our adaptive mesh refinement is done within a small tube of |phi(x,y)|<= delta with finer Cartesian meshes. The discrete linear system of equations is solved by a multigrid solver. The AMR methods could obtain solutions with accuracy that is similar to those on a uniform fine grid by distributing the mesh more economically, therefore, reduce the size of the linear system of the equations. Numerical examples presented show the efficiency of the grid refinement strategy. PMID- 22670156 TI - A case report: lobular carcinoma in situ in a male patient with subsequent invasive ductal carcinoma identified on screening breast MRI. AB - Lobular carcinoma in situ is a form of in situ neoplasia that develops within the terminal lobules of the breast. It is an extremely rare finding in males due to the lack of lobular development in the male breast. The authors herein report an unusual case of incidentally discovered lobular carcinoma in situ in a male patient with recurrent bilateral gynecomastia who was subsequently diagnosed with invasive ductal carcinoma of the left breast. The pathology of lobular carcinoma in situ in a male as well as screening MRI surveillance of male patients at high risk for breast cancer are discussed, emphasizing the importance of screening and imaging follow up in men who are at high risk for breast cancer. PMID- 22670157 TI - A Pilot Study Assessing the Potential Role of non-CD133 Colorectal Cancer Stem Cells as Biomarkers. AB - INTRODUCTION: Over 50% of patients with colorectal cancer (CRC) will progress and/or develop metastases. Biomarkers capable of predicting progression, risk stratification and therapeutic benefit are needed. Cancer stem cells are thought to be responsible for tumor initiation, dissemination and treatment failure. Therefore, we hypothesized that CRC cancer stem cell markers (CRCSC) will identify a group of patients at high risk for progression. METHODS: Paraffin embedded tissue cores of normal (n=8), and histopathologically well-defined primary (n= 30) and metastatic (n=10) CRC were arrayed in duplicate on tissue microarrays (TMAs). Expression profiles of non-CD133 CRCSC (CD29, CD44, ALDH1A1, ALDH1B1, EpCam, and CD166) were detected by immunohistochemistry and the association with clinicopathological data and patient outcomes was determined using standard statistical methodology. An independent pathologist, blinded to the clinical data scored the samples. Scoring included percent positive cells (0 to 4, 0 = <10%, 1 = 10 - 24%, 2 = 25 - 49%, 3 = 50 - 74%, 4 = 75 - 100%), and the intensity of positively stained cells (0 to 4; 0 = no staining, 1 = diminutive intensity, 2 = low intensity, 3 = intermediate intensity, 4 = high intensity). The pathologic score represents the sum of these two values, reported in this paper as a combined IHC staining score (CSS). RESULTS: Of 30 patients 7 were AJCC stage IIA, 10 stage IIIB, 7 stage IIIC and 6 stage IV. Median follow-up was 113 months. DFI was 17 months. Median overall survival (OS) was not reached. Stage specific OS was: II - not reached; III - not reached; IV - 11 months. In a univariate analysis, poor OS was associated with loss of CD29 expression; median OS, 32 months vs. not reached for CSS 3-7 vs. >7.5, respectively; p=0.052 comparing entire curves, after adjustment. In a Cox model analysis, loss of CD29 exhibited a trend toward association with survival (p=0.098) after adjusting for the effect of stage (p=0.0076). Greater expression of ALDH1A1 was associated with increasing stage (p=0.042 over stages 2, 3b, 3c, and 4) while loss of CD29 expression exhibited a trend toward being associated with stages 3 and 4 (p=0.08). Compared to normal colon tissue, primary tumors were associated with increased expression of ALDH1B1 (p=0.008). ALD1H1B1 expression level differed according to whether the tumor was moderately or poorly differentiated, well differentiated, or mucinous; the highest expression levels were associated with moderately or poorly differentiated tumors (p=0.011). Lymph node metastases were associated with a trend toward decreased expression of EpCAM (p = 0.06) when comparing 0 vs. 1 vs. 2+ positive lymph nodes, as was CD29 (p = 0.08) when comparing 0 vs. any positive lymph nodes. Compared to normal colon tissue metastatic colon cancers from different patients were associated with increased ALDH1B1 expression (p=0.001) whereas CD29 expression was higher in normal colonic tissue (p=0.014). CONCLUSION: CD29 may be associated with survival as well as clinical stage and number of lymph nodes. ALDH1B1 expression was associated with differentiation as well as type of tissue evaluated. ALDH1A1 was associated with clinical stage, and decreased EpCAM expression was found in patients with advanced lymph node stage. CRCSCs may be useful biomarkers to risk stratify, and estimate outcomes in CRC. Larger prospective studies are required to validate the current findings. PMID- 22670158 TI - FDG PET/CT Response Evaluation in Malignant Pleural Mesothelioma Patients Treated with Talc Pleurodesis and Chemotherapy. AB - PURPOSE: Talc pleurodesis (TP) is employed worldwide for the management of persistent pneumothorax or pleural effusion, particularly of malignant origin. However, there are very little available data on (18)F-fluorodeoxyglucose positron-emission tomography/computed tomography ((18)F FDG PET/CT) response evaluation in malignant pleural mesothelioma (MPM) patients treated with TP and chemotherapy. METHODS: Patients with histologically confirmed MPM underwent TP and FDG PET/CT staging and restaging after 3-4 courses of chemotherapy. All patients fasted and received a dose of 5.18 MBq (18)F-FDG per kilogram of body weight. Whole-body emission scans were acquired with and without Ordered Subset Expectation Maximization (OSEM) iterative reconstruction algorithm. RESULTS: From January 2004 to March 2010, 8 patients with biopsy confirmed MPM (7 epithelial, 1 biphasic), with a median age of 65 years (range: 54-77), were evaluated. Median follow-up was 31 months (range: 4-44). After TP treatment, there was a mean interval of 14 days (range: 9-22) and 125 days (range: 76-162) between FDG PET/CT staging and restaging. According to modified RECIST and EORTC criteria, there was a concordance between the radiologic and metabolic SUVmean and SUVmax responses in 6 (75%) and 3 (37.5%) patients, respectively. CONCLUSION: TP produces an increased FDG PET uptake which may interfere with the post-chemotherapy disease evaluation. In our case series, the metabolic response measured by SUVmean seems to be in better agreement with the radiologic response compared to the SUVmax. PMID- 22670159 TI - PEEK (Polyether-ether-ketone) Based Cervical Total Disc Arthroplasty: Contact Stress and Lubrication Analysis. AB - This paper presents a theoretical analysis of the maximum contact stress and the lubrication regimes for PEEK (Polyether-ether-ketone) based self-mating cervical total disc arthroplasty. The NuNec((r)) cervical disc arthroplasty system was chosen as the study object, which was then analytically modelled as a ball on socket joint. A non-adhesion Hertzian contact model and elastohydrodynamic lubrication theory were used to predict the maximum contact stress and the minimum film thickness, respectively. The peak contact stress and the minimum film thickness between the bearing surfaces were then determined, as the radial clearance or lubricant was varied. The obtained results show that under 150 N loading, the peak contact stress was in the range 5.9 - 32.1 MPa, well below the yield and fatigue strength of PEEK; the calculated minimum film thickness ranged from 0 to 0.042 um and the corresponding lambda ratio range was from 0 to 0.052. This indicates that the PEEK based cervical disc arthroplasty will operate under a boundary lubrication regime, within the natural angular velocity range of the cervical spine. PMID- 22670160 TI - Thrombospondin-1 in early flow-related remodeling of mesenteric arteries from young normotensive and spontaneously hypertensive rats. AB - We tested the hypotheses that TSP-1 participates in the initiation of remodeling of small muscular arteries in response to altered blood flow and that the N terminal domain of TSP-1 (hepI) can reverse the pathological inward remodeling of resistance arteries from SHR.We measured (1) changes in gene/protein expression in MA of 6 week old WKY and SHR exposed to either increased (+ 100 %) or reduced blood flow (- 90 %) for 24-40 hours and (2) structural changes in MA of 12 week old SHR exposed for 3 days to hepI in organ culture.In both HF and LF of WKY, mRNA expression of eNOS, sGCalpha1 and PKG1beta were significantly reduced (p < 0.05), whereas mRNA of TSP1 was markedly increased (p < 0.05). In MA of young SHR, similar results were obtained except that eNOS mRNA was not reduced in LF. Expression of TSP1 protein was significantly increased in LF of young WKY and SHR (p < 0.05). Exposure of MA of 12 week old SHR to hepI (1 umol/L) resulted in a rapid lumen diameter increase (+ 12 +/- 2% after 3 days) without alteration in vascular reactivity, distensibility, media surface area or cell number.These are the first observations of reduced gene expression of eNOS/sGC/PKG and increased expression of TSP1 at the initiation of arterial remodeling in young WKY and SHR, irrespective of its outward or inward outcome. Furthermore, a fragment of TSP-1 rapidly and directly reversed pathological inward arterial remodeling of SHR in vitro. PMID- 22670161 TI - Effect of age on clinical presentation and outcome of patients hospitalized with acute coronary syndrome: a 20-year registry in a middle eastern country. AB - INTRODUCTION: Despite the fact that the elderly constitute an increasingly important group of patients with acute coronary syndrome (ACS), they are often excluded from clinical trials and are underrepresented in clinical registries. AIMS: To evaluate the impact of age in patients hospitalized with ACS. METHODS: Data collected for all patients presenting with ACS (n=16,744) who were admitted in Qatar during the period (1991-2010) and were analyzed according to age into 3 groups (<=50 years [41.4%], 51-70 years [48.7%] and >70 years [9.8%]). RESULTS: Older patients were more likely to be women and have hypertension, diabetes mellitus, and renal failure, while younger patients were more likely to be smokers. Non-ST-elevation myocardial infarction and heart failure were more prevalent in older patients. Older age was associated with undertreatment with evidence-based therapies and had higher mortality rate. Age was independent predictor for mortality. Over the study period, the relative reduction in mortality rates was higher in the younger compared with the older patients (61, 45.9 and 35.5%). CONCLUSIONS: Despite being a higher-risk group, older patients were undertreated with evidence based therapy and had worse short-term outcome. Guidelines adherence and improvement in hospital care for elderly patients with ACS may potentially reduce morbidity and mortality. PMID- 22670162 TI - Responses to Cortical Spreading Depression under Oxygen Deficiency. AB - OBJECTIVES: OBJECTIVES: The effect of cortical spreading depression (CSD) on extracellular K(+) concentrations ([K(+)](e)), cerebral blood flow (CBF), mitochondrial NADH redox state and direct current (DC) potential was studied during normoxia and three pathological conditions: hypoxia, after NOS inhibition by L-NAME and partial ischemia. METHODS: A SPECIAL DEVICE (MPA) WAS USED FOR MONITORING CSD WAVE PROPAGATION, CONTAINING: mitochondrial NADH redox state and reflected light, by a fluorometry technique; DC potential by Ag/AgCl electrodes; CBF by laser Doppler flowmetry; and [K(+)](e) by a mini-electrode. RESULTS AND DISCUSSION: CSD under the 3 pathological conditions caused an initial increase in NADH and a further decrease in CBF during the first phase of CSD, indicating an imbalance between oxygen supply and demand as a result of the increase in oxygen requirements. The hyperperfusion phase in CBF was significantly reduced during hypoxia and ischemia showing a further decline in oxygen supply during CSD. CSD wave duration increased during the pathological conditions, showing a disturbance in energy production.Extracellular K(+) levels during CSD, increased to identical levels during normoxia and during the three pathological groups, indicating correspondingly increase in oxygen demand. 5. The special design of the MPA enabled identifying differences in the simultaneous responses of the measured parameters, which may indicate changes in the interrelation between oxygen demand, oxygen supply and oxygen balance during CSD propagation, under the conditions tested. 6. In conclusion, brain oxygenation was found to be a critical factor in the responses of the brain to CSD. PMID- 22670163 TI - Characterisation of the MutS and MutL Proteins from the Pseudomonas avellanae Mismatch Repair (MMR) System. AB - The identification and analysis of the Pseudomonas avellanae mismatch repair system (MMR) were performed via sequencing and cloning the mutS and mutL genes and then analyzing the characteristics of the corresponding proteins studying their function and biological role in an E. coli heterologous system. In these studies, the P. avellanae MutS and MutL proteins were shown to localise at the nucleoid level, in a MutS-dependent manner as far as MutL is concerned, and were also able to complement the defect observed in both the mutS and mutL knockout strains of E. coli. In addition, their ability to form both homo and heterodimers between each other was shown by using the prokaryotic two-hybrid assay. Our results represent a first step to elucidate the MMR mechanism in plant pathogenic pseudomonads since the MMR genes were identified in P. syringae pathovars but there was no evidence on their action as effective repair products. PMID- 22670164 TI - Body mass index, gender, and ethnic variations alter the clinical implications of the epworth sleepiness scale in patients with suspected obstructive sleep apnea. AB - INTRODUCTION: The Epworth Sleepiness Scale (ESS) is often used in the evaluation of obstructive sleep apnea (OSA), though questions remain about the influence gender, ethnicity, and body morphometry have in the responses to this questionnaire. The aim of this study was to examine differences in ESS scores between various demographic groups of patients referred for polysomnography, and the relationship of these score to sleep-disordered breathing METHODS: Nineteen hundred consecutive patients referred for polysomnographic diagnosis of OSA completed questionnaires, including demographic data and ESS. OSA was determined based on a respiratory disturbance index (RDI) >=15 by polysomnography. RESULTS: In this high risk population for OSA, the ESS was 10.7 +/- 5.6. The highest ESS scores were seen in obese males; non-obese females and non-obese Caucasian males scored the lowest. ESS was weakly correlated with RDI (r = 0.17, P < 0.0001). The sensitivity of ESS for the diagnosis of OSA was 54% and the specificity was 57%. The positive (PPV) and negative (NPV) predictive values were 64% and 47%, respectively. In obese subjects, the sensitivity and specificity were 55% and 53%, compared with 47% and 63% in non-obese subjects. In obese, Hispanic males, the sensitivity, specificity, and PPV were 59%, 54%, and 84%, respectively. In non-obese, Caucasian females, the sensitivity, specificity, and NPV were 43%, 59%, and 72%. CONCLUSIONS: The ESS appears to be affected by many factors, including gender, ethnicity, and body morphometry. The ability of the ESS to predict OSA is modest, despite a significant correlation with the severity of OSA. The test characteristics improve significantly when applied to select populations, especially those at risk for OSA. PMID- 22670165 TI - Renal perfusion in scleroderma patients assessed by microbubble-based contrast enhanced ultrasound. AB - OBJECTIVES: Renal damage is common in scleroderma. It can occur acutely or chronically. Renal reserve might already be impaired before it can be detected by laboratory findings. Microbubble-based contrast-enhanced ultrasound has been demonstrated to improve blood perfusion imaging in organs. Therefore, we conducted a study to assess renal perfusion in scleroderma patients utilizing this novel technique. MATERIALS AND METHODOLOGY: Microbubble-based contrast agent was infused and destroyed by using high mechanical index by Siemens Sequoia (curved array, 4.5 MHz). Replenishment was recorded for 8 seconds. Regions of interests (ROI) were analyzed in renal parenchyma, interlobular artery and renal pyramid with quantitative contrast software (CUSQ 1.4, Siemens Acuson, Mountain View, California). Time to maximal Enhancement (TmE), maximal enhancement (mE) and maximal enhancement relative to maximal enhancement of the interlobular artery (mE%A) were calculated for different ROIs. RESULTS: There was a linear correlation between the time to maximal enhancement in the parenchyma and the glomerular filtration rate. However, the other parameters did not reveal significant differences between scleroderma patients and healthy controls. CONCLUSION: Renal perfusion of scleroderma patients including the glomerular filtration rate can be assessed using microbubble-based contrast media. PMID- 22670166 TI - Very early anthropometric changes after antiretroviral therapy predict subsequent survival, in karonga, Malawi. AB - BACKGROUND: Antiretroviral (ART) scale-up in Malawi has been achieved on a large scale based mainly on clinical criteria. Simple markers of prognosis are useful, and we investigated the value of very early anthropometric changes in predicting mortality. METHODS: PRINCIPAL FINDINGS: Adult patients who initiated ART in Karonga District, northern Malawi, between September 2005 and August 2006 were included in a prospective cohort study, and followed for up to one year. We used Cox regression to examine the association between anthropometric changes at 2 and 6 weeks and deaths within the first year. 573 patients were included, of whom 59% were women; the median age at initiation was 37 and 64% were in WHO stage 4. Both body mass index (BMI) and mid-upper arm circumference (MUAC) increased linearly with increased time on ART, and were closely correlated with each other. There were 118 deaths. After 2 weeks on ART, a BMI increase of <0.5 kg/m(2) (HR 2.47, 95%CI 1.24-4.94, p=0.005) or a MUAC increase of <0.5cm (HR 2.79, 95%CI 1.19-6.55, p=0.008) were strong predictors of death, and these associations were stronger after adjusting for baseline charactertistics. Similar results were found after 6 weeks on ART. CONCLUSIONS: Very early anthropometric changes, after 2 and 6 weeks on ART, are strong predictors of survival, independent of baseline characteristics. This should help identify patients requiring more detailed assessment where facilities are limited. MUAC is particularly valuable, requiring the simplest equipment and being appropriate for patients who have problems standing. PMID- 22670167 TI - Density-dependent separation of encapsulated cells in a microfluidic channel by using a standing surface acoustic wave. AB - This study presents a method for density-based separation of monodisperse encapsulated cells using a standing surface acoustic wave (SSAW) in a microchannel. Even though monodisperse polymer beads can be generated by the state-of-the-art technology in microfluidics, the quantity of encapsulated cells cannot be controlled precisely. In the present study, mono-disperse alginate beads in a laminar flow can be separated based on their density using acoustophoresis. A mixture of beads of equal sizes but dissimilar densities was hydrodynamically focused at the entrance and then actively driven toward the sidewalls by a SSAW. The lateral displacement of a bead is proportional to the density of the bead, i.e., the number of encapsulated cells in an alginate bead. Under optimized conditions, the recovery rate of a target bead group (large-cell quantity alginate beads) reached up to 97% at a rate of 2300 beads per minute. A cell viability test also confirmed that the encapsulated cells were hardly damaged by the acoustic force. Moreover, cell-encapsulating beads that were cultured for 1 day were separated in a similar manner. In conclusion, this study demonstrated that a SSAW can successfully separate monodisperse particles by their density. With the present technique for separating cell-encapsulating beads, the current cell engineering technology can be significantly advanced. PMID- 22670168 TI - Microfluidic device for studying cell migration in single or co-existing chemical gradients and electric fields. AB - Cell migration is involved in physiological processes such as wound healing, host defense, and cancer metastasis. The movement of various cell types can be directed by chemical gradients (i.e., chemotaxis). In addition to chemotaxis, many cell types can respond to direct current electric fields (dcEF) by migrating to either the cathode or the anode of the field (i.e., electrotaxis). In tissues, physiological chemical gradients and dcEF can potentially co-exist and the two guiding mechanisms may direct cell migration in a coordinated manner. Recently, microfluidic devices that can precisely configure chemical gradients or dcEF have been increasingly developed and used for chemotaxis and electrotaxis studies. However, a microfluidic device that can configure controlled co-existing chemical gradients and dcEF that would allow quantitative cell migration analysis in complex electrochemical guiding environments is not available. In this study, we developed a polydimethylsiloxane-based microfluidic device that can generate better controlled single or co-existing chemical gradients and dcEF. Using this device, we showed chemotactic migration of T cells toward a chemokine CCL19 gradient or electrotactic migration toward the cathode of an applied dcEF. Furthermore, T cells migrated more strongly toward the cathode of a dcEF in the presence of a competing CCL19 gradient, suggesting the higher electrotactic attraction. Taken together, the developed microfluidic device offers a new experimental tool for studying chemical and electrical guidance for cell migration, and our current results with T cells provide interesting new insights of immune cell migration in complex guiding environments. PMID- 22670169 TI - In situ pressure measurement within deformable rectangular polydimethylsiloxane microfluidic devices. AB - In this paper, we present a simple procedure to incorporate commercially available external pressure transducers into existing microfluidic devices, to monitor pressure-drop in real-time, with minimal design modifications to pre existing channel designs. We focus on the detailed fabrication steps and assembly to make the process straightforward and robust. The work presented here will benefit those interested in adding pressure drop measurements in polydimethylsiloxane (PDMS) based microchannels without having to modify existing channel designs or requiring additional fabrication steps. By using three different devices with varying aspect ratio channels ([Formula: see text], width/depth), we demonstrate that our approach can easily be adapted into existing channel designs inexpensively. Furthermore, our approach can achieve steady state measurements within a matter of minutes (depending on the fluid) and can easily be used to investigate dynamic pressure drops. In order to validate the accuracy of the measured pressure drops within the three different aspect ratio devices, we compared measured pressure drops of de-ionized water and a 50 wt. % glycerol aqueous solution to four different theoretical expressions. Due to the deformability of PDMS, measured pressure drops were smaller than those predicted by the rigid channel theories (plate and rectangular). Modification of the rigid channel theories with a deformability parameter alpha provided better fits to the measured data. The elastic rectangular expression developed in this paper does not have a geometric restriction and is better suited for microchannels with a wider range of aspect ratios. PMID- 22670170 TI - Shape controllable microgel particles prepared by microfluidic combining external ionic crosslinking. AB - Alginate microgels with varied shapes, such as mushroom-like, hemi-spherical, red blood cell-like, and others, were generated by combining microfluidic and external ionic crosslinking methods. This novel method allows a continuous fine tuning of the microgel particles shape by simply varying the gelation conditions, e.g., viscosity of the gelation bath, collecting height, interfacial tension. The release behavior of iopamidol-loaded alginate microgel particles with varied morphologies shows significant differences. Our technique can also be extended to microgels formation from different anionic biopolymers, providing new opportunities to produce microgels with various anisotropic dimensions for the applications in drug delivery, optical devices, and in advanced materials formation. PMID- 22670171 TI - Aldo-keto reductase family 1 member C3 (AKR1C3) is expressed in adenocarcinoma and squamous cell carcinoma but not small cell carcinoma. AB - Human aldo-keto reductase family 1 member C3 (AKR1C3) was initially identified as a critical enzyme in reducing 5alpha-dihydrotestosterone (5alpha-DHT) to 5alpha androstane-3alpha,17beta-diol (3alpha-diol) and oxidizing 3alpha-diol to androsterone. Based on these enzymatic activities, AKR1C3 was originally named type 2 3alpha-hydroxysteroid dehydrogenase (HSD)/type 5 17beta-HSD. Additionally, AKR1C3 was demonstrated to be capable of metabolizing other steroids including estrogen and progesterone. Subsequently, AKR1C3 was shown to possess 11 ketoprostaglandin reductase activity in metabolizing prostaglandins and dihydrodiol dehydrogenase x (DDx) activity in metabolizing xenobiotics. Tissue distribution of AKR1C3 has been detected in both sex hormone-dependent organs such as the testis, breast, endometrium, and prostate as well as sex hormone independent organs including the kidney and urothelium. Although prominent expression of AKR1C isozymes has been reported in human non-small cell lung carcinoma (NSCLC), the expression of AKR1C3 in small cell carcinoma of the lung has not been described. Also, the expression of AKR1C3 in normal lung has not been described. In this study, we demonstrated strong AKR1C3 immunoreactivity in bronchial epithelium but not in bronchial glands or alveolar pneumocytes. Strong AKR1C3 immunoreactivity was also demonstrated in columnar epithelium but only weak immunoreactivity in squamous epithelium of the gastrointestinal junction. Although AKR1C3 immunoreactivity was absent in small cell carcinoma of the lung, positive AKR1C3 immunoreactivity was extensively present in both adenocarcinoma and squamous cell carcinoma arising from the lung and the gastroesophageal junction. AKR1C3 may serve as an adjunct marker for differentiating small cell carcinoma from NSCLC. However, roles of AKR1C3 in adenocarcinoma, squamous cell carcinoma, and small cell carcinoma pathogenesis require further studies. PMID- 22670172 TI - Lentivirus-mediated RNAi knockdown of VEGFA in RKO colorectal cancer cells decreases tumor formation and growth in vitro and in vivo. AB - Vascular endothelial growth factors (VEGF) play important roles in angiogenesis, vasculogenesis and endothelial cell growth. In endothelial cancers, secreted VEGF proteins induce endothelial cell proliferation, promote cell migration, inhibit apoptosis and induce blood vessel permeabilization. VEGFA is frequently overexpressed in human colorectal cancers (CRC) and its expression correlates with tumor progression and invasiveness. In this study we examine the effect of knocking down VEGFA expression by infecting RKO colorectal cancer cells with lentiviral particles containing VEGFA-targeting RNAi constructs. We found that suppressing VEGFA dramatically decreased RKO cell proliferation, colony formation, invasion, migration and tumor growth. Furthermore, VEGFA knock-down reduced MAPK pathway signaling and Smac/DIABLO expression. These results suggest that lentivirus-mediated RNAi knock-down of VEGFA could be an effective therapy for the treatment of CRC. PMID- 22670174 TI - Histologic evaluation of intrahepatic micrometastases in patients treated with or without neoadjuvant chemotherapy for colorectal carcinoma liver metastasis. AB - In the present retrospective study, we tested the hypothesis that neoadjuvant chemotherapy (NAC) as a treatment for patients with colorectal carcinoma liver metastases (CRLM) may reduce intrahepatic micrometastases. The incidence and distribution of intrahepatic micrometastases were determined in specimens resected from 63 patients who underwent hepatectomy for CRLM (21 treated with NAC and 42 without). In addition, the therapeutic efficacy of NAC was evaluated histologically. Intrahepatic micrometastases were defined as microscopic lesions spatially separated from the gross tumor. The distance from these lesions to the border of the hepatic tumor was measured on histological specimens and the density of intrahepatic micrometastases (number of lesions/mm(2)) was determined in regions close to (<1 cm) the gross hepatic tumor. Of the 21 patients treated with NAC, 13 were identified as having a partial response according to the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines; thus, the overall response rate was 62%. Histologic evaluation of the therapeutic efficacy of NAC was significantly associated with tumor response to NAC according to the RECIST guidelines (p=0.048). In all, 260 intrahepatic micrometastases were detected in 39 patients (62%). Intrahepatic micrometastases were less frequently detected in NAC-treated patients than in untreated patients (5/21 [24%] vs. 34/42 [81%], respectively; p<0.001). There were no significant differences in the distance and density of intrahepatic micrometastases between the two groups (p=0.313 and p=0.526, respectively). In conclusion, NAC reduces the incidence of intrahepatic micrometastases in patients with CRLM, but NAC has no significant effect on their distribution when intrahepatic micrometastases are present. PMID- 22670173 TI - CsA improves the trophoblasts invasiveness through strengthening the cross-talk of trophoblasts and decidual stromal cells mediated by CXCL12 and CD82 in early pregnancy. AB - Our previous work has demonstrated that cyclosporin A (CsA) up-regulates but CD82 down-regulates the invasiveness of human trophoblasts. In the present study, we further investigated whether CsA can modulate the trophoblasts invasion through regulating the expression of CD82 in decidual stromal cells (DSCs). A co-culture model was established to investigate the effect of CsA on trophoblasts invasiveness. In-cell Western was performed to evaluate the expression of CD82, p53, beta-catenin and the phosphorylation level of NF-kappaB p50 in DSCs. The secretion of CXCL12 of trophoblasts and DSCs was determined by enzyme-linked immunosorbent assay (ELISA). We found that CsA could not directly change the expression of CD82 in DSCs, but the CsA-treated trophoblasts significantly enhanced CD82 expression, NF-kappaB p50 phosphorylation and p53 expression, and decreased beta-catenin expression in DSCs, and these effects could be abolished by anti-CXCL12 or CXCR4 neutralizing antibody. In addition, the invasiveness of trophoblast cells was markedly decreased after blocking CXCR4 of trophoblasts. Interestingly, when DSCs were pretreated with anti-CXCR4 neutralizing antibody, the invasiveness of trophoblast cells was enhanced in the coculture unit, and blocking CXCR4 on DSCs could reverse the decrease of trophoblasts invasiveness induced by CD82. Moreover, CsA further amplified these effects mediated by CXCL12 and CD82. Our results suggest that CsA not only promotes the trophoblasts invasiveness through stimulating the secretion of CXCL12, but also limits the invasiveness of trophoblasts by indirectly up-regulating the expression CD82. Therefore, CsA may contribute to the appropriate invasiveness of trophoblasts via strengthening the crosstalk between trophoblasts and DSCs. PMID- 22670175 TI - The PIWI protein acts as a predictive marker for human gastric cancer. AB - PURPOSE: To investigate the expression of the human PIWI subfamily proteins in gastric cancer and their potential roles in the occurrence, development and prognosis of gastric cancer. METHODS AND PATIENTS: Expression of the PIWI proteins were assessed by immunohistochemistry (IHC) in tissue microarrays (TMA), containing paired tumor tissue and adjacent non-cancer tissue from 182 patients who had undergone surgery in hospital for histologically proven gastric cancer (GC). Prognostic value and correlation with other clinicopathologic factors were evaluated in two classifications. RESULTS: The expression of PIWIL1-4 was significantly higher in tumor tissue than that in adjacent tissue; A significant correlation was observed between the higher expression of PIWI protein with the T stage, lymph node metastasis and clinical TNM (cTNM); Survival analysis by Kaplan Meier survival curve and log-rank test demonstrated that elevated PIWIL1 and PIWIL2 expression in cancer tissue predicted poorer overall survival (OS) compared with group in lower expression (36.5% VS 67.6%; 37.4% VS 54.2%; respectively). Notably, multivariate analyses by Cox's proportional hazard model revealed that expression of PIWIL1 was an independent prognostic factor in gastric cancer. CONCLUSIONS: The PIWI subfamily protein is an absolutely key molecular factor along with the tumor occurrence and development. And the PIWI protein could act as a potential biomarker for prognosis evaluation of gastric cancer. PMID- 22670176 TI - Necrotic epithelial cells in proximal renal tubules of 2nd trimester fetuses: is this "acute tubular necrosis"? AB - PURPOSE: The aim of this study is to describe the occurrence of necrotic tubular cells in kidneys of non-macerated fetuses. METHODS: Description of histology and immunostaining results using C9 immunostain of proximal tubular epithelium of kidneys from 30 consecutive non-macerated fetuses' autopsies. RESULTS: the gestational age ranged from 13 to 22 weeks. The mean gestational age was 18.6 weeks; the cause of death was acute chorioamnionitis in 13 cases (43.3%), termination of pregnancy for fetal anomalies in 13 (43.3%) and other causes in 4 (13.3%). Histology of the kidneys revealed vacuolation of proximal tubule epithelial cells (100%), dilatation of tubules (93.4%) and tubular cell necrosis (53.4%). C9 immunostaining was positive in 24 cases (80%) and was seen in all gestational ages. CONCLUSIONS: These results indicate that tubular cell necrosis is not an uncommon finding in the kidneys of 2(nd) trimester fetuses and may represent acute tubular necrosis (ATN). C9 is a helpful marker in confirming this diagnosis. Future studies may further explore this preliminary observation. PMID- 22670177 TI - An immunohistochemical and molecular genetic analysis of KIT and PDGFRA in small cell lung carcinoma in Japanese. AB - KIT and PDGFRA in small cell lung carcinoma (SCLC) have been rarely examined in Japanese. The author investigated protein expression of KIT and PDGFRA in 54 Japanese cases of small cell lung carcinoma by immunohistochemistry, and gene mutations of KIT and PDGFRA in 20 Japanese cases of small cell lung carcinoma by the PCR-direct sequencing method. The molecular genetic analysis showed no mutations of KIT (exons 9, 11, 13, and 17) and PDGFRA (exons 12 and 18) genes in all 20 cases. KIT protein expression was recognized in all cases (100%). Membranous KIT expression was strong in 35 cases, moderate in 7 cases and weak in 12 cases. PDGFRA protein expression was noted in 35 cases (65%); the membranous expression was strong in 2 cases, moderate in 16 cases, and weak in 17 cases. The overall median survival was 13 months. There was no significant difference in the survival between KIT strongly positive cases (median, 12 months) and KIT moderately or weakly positive cases (median, 11 months). Likewise, there was no significant difference in the survival between PDGFRA-positive cases (median, 11 months) and PDGFRA-negative cases (median, 12 months). The protein expressions of KIT and PDGFRA did not correlate with gender, smoking, and disease stage. These findings suggest, in Japanese population, that mutations of KIT and PDGFRA were absent in small cell lung carcinoma of Japan, that KIT protein expression is present in 100%, that PDGFRA expression is present in 65%, and that KIT and PDGFRA protein expressions do not correlate with survival, gender, smoking, and disease stage. PMID- 22670178 TI - Expression of c-Myc and Fas correlates with perineural invasion of pancreatic cancer. AB - Lymph node metastasis (LNM) and perineural invasion (PNI) are regarded as two important prognostic factors in pancreatic cancer. The aim of this study was to identify the LNM-associated and PNI-associated markers in pancreatic cancer. We have constructed a formalin-fixed paraffin embedded pancreatic tissue microarrays containing 324 cylindrical tissue cores of human pancreatic cancer and its paracancerous nonmalignant pancreatic specimens (NMPs) from 162 patients. Among those patients, there were 83 of 162 with PNI, and 65 of 162 with LNM. The protein products of 2 genes encompassing a variety of functional classes, such as oncogenes (c-Myc), apoptosis (Fas), were analyzed by immunohistochemistry on the tissue microarray. There was marked increase in cancer tissues cytoplasmic c-Myc expression level in pancreatic cancer compared with the NMPs (P < 0.0001). Additionally, the expression level of c-Myc was also significant increase in pancreatic cancer with PNI compared with cancer without PNI (P < 0.01). In contrast, cytoplasmic Fas, low expressed in pancreatic cancer (P < 0.0001) was negatively correlated with PNI (P < 0.05). Logistic regression analysis showed that the c-Myc expression in the cancer tissues cytoplasm acted as a potential and independently predictive factor for PNI. However, there were no significant association between the expression of these two genes and LNM (P > 0.05). This study for the first time described expression levels of c-Myc and Fas played an important role in PNI of pancreatic cancer. Combined detection can be used as predictive factors, especially c-Myc. PMID- 22670179 TI - Ribonucleotide reductase M2 does not predict survival in patients with resectable pancreatic adenocarcinoma. AB - BACKGROUND: Ribonucleotide reductase M2 (RRM2) was associated with pancreatic tumor progression and resistance to gemcitabine. This study aimed to determine if RRM2 protein expression was prognostic in patients with resectable pancreatic adenocarcinoma and predictive of adjuvant gemcitabine benefit. METHODS: 117 patients underwent tumor resection for pancreatic adenocarcinoma from 10/1999 to 12/2007. We constructed tissue microarrays from paraffin-embedded tumors and determined RRM2 protein expression using immunohistochemistry and grouped as negative or positive. We estimated overall survival (OS) and progression-free survival (PFS) using the Kaplan-Meier method and examined the prognostic and predictive value of RRM2 expression using Cox proportional hazards model. RESULTS: RRM2 expression showed no prognostic value in the entire group regarding OS (median OS 30.9 months in RRM2-positive versus 13.7 months in RRM2-negative, P = 0.26) and PFS (median OS 20.6 months in RRM2-positive versus 11.8 months in RRM2-negative, P = 0.46). RRM2 expression did not predict adjuvant gemcitabine benefit in the subgroup of 44 patients who received gemcitabine therapy (median OS 31.2 versus 15.2 months, P = 0.62; median PFS 11.3 versus 14.0 months, P = 0.35). Cox proportional hazards regression showed no prognostic effect of RRM2 expression on OS and PFS in the subgroup of 44 patients. However, the number of positive lymph nodes and perineural invasion were prognostic factors for OS (HR 1.2, P = 0.005) and for PFS (HR 5.5, P = 0.007), respectively. CONCLUSION: RRM2 protein expression in pancreatic adenocarcinoma is neither prognostic nor predictive of adjuvant gemcitabine benefit in patients with resectable pancreatic adenocarcinoma. PMID- 22670180 TI - Plasmacytoid adenocarcinoma of the lung. AB - Plasmacytoid adenocarcinoma of the lung has not been reported. Herein reported is the first case of plasmacytoid adenocarcinoma of the lung. A 68-year-old man presented with cough and sputum. X-P and CT demonstrated a large tumor (10 x 10 x 9 cm) in the right upper lobe. CT-guided needle biopsy was performed. The biopsy showed plasmacytoid malignant cells. The malignant cells were small, had eccentrically located nuclei, perinuclear halo, and basophilic cytoplasm. No mucins were observed by mucins stains. Immunohistochemical study showed that the tumor cells were positive for pancytokeratin AE1/3, pancytokeratin CAM5.2, TTF-1, Ki-67 (labeling 70%), CA19-9, and p53. They were negative for neuron specific enolase, CEA, CD45, CD68, chromogranin, synaptophysin, surfactant apoprotein A, CDX-2, kappa-chain, lambda-chain, KIT, and PDGFRA. Since epithelial markers and adenocarcinoma markers were positive, the pathological diagnosis was plasmacytoid adenocarcinoma of lung. The patient is now treated with chemotherapy. PMID- 22670181 TI - The efficacy of EBER in situ hybridization (ISH) stain in PTLD (malignant diffuse large B-cell lymphoma) about 4 years after ABO-incompatible kidney transplantation: a case report. AB - Post-transplant lymphoproliferative disease (PTLD) is a well-known late complication of organ transplantation which incidence has increased after the introduction of more powerful immunosuppressive agents. A 58-year-old man performed ABO-incompatible living kidney transplantation in June, 2008. At 3 years and 9 months after the transplantation, the patient complained of general fatigue and dyspnea and was hospitalized with renal dysfunction. The clinical data in hospital showed acute rejection, but soluble IL-II exceeded 21700U/ml, and HE staining kidney graft showed a massive infiltration of atypical lymphocytes. Atypical lymphocytes were positive for L-26 and negative for CD3 immunochemical stein, and the EBER in situ hybridization stain for EBV was negative in renal graft. We diagnosed diffuse large B-cell lymphoma in the kidney graft. However, he died due to multiple organ failure (MOF). We described a fatal case of diffuse large B-cell lymphoma without EBV infection occurring 3 years 9 months after ABO-incompatible kidney transplantation. Unfortunately, post-mortem autopsy using EBER-ISH stain does not show whether EB virus infection was a cause. PMID- 22670182 TI - Squamous cell carcinoma arising within verrucous carcinoma of the oral cavity: a case report. AB - The author herein reports a case of squamous cell carcinoma (SCC) arising within verrucous carcinoma (VC) of the hard palate. An 84-year-old woman was admitted to our hospital complaining of oral discomfort. Oral examination revealed a pedunculated verrucous tumor (15 x 15 mm) in the hard palate. A biopsy revealed verrucous tumor. Resection of the lesion with wide margins was performed. Grossly, the palate tumor was pedunculated and verrucous, but a depressed area (8 x 7 mm) was recognized. Microscopically, the verrucous ares showed verrucous proliferation of squamous epithelium with little cellular atypia, and was interpreted as VC without invasion. The depressed lesion was obvious SCC with invasion. There were direct transitions between the VC and SCC. Immunohistochemically, the VC and SCC tumor cells were negative for human papilloma virus antigens. P53 protein was expressed in both VC and SCC, though the expression in SCC was much more strong and broad than that in VC. The Ki-67 antigen was also expressed in the VC and SCC, and Ki-67 labeling index ranged was 12% in VC and 64% in SCC. These findings indicate that SCC may arise within VC. PMID- 22670184 TI - Giant cell tumor of the tendon sheath composed largely of epithelioid histiocytes. AB - Giant cell tumor of the tendon sheath (GCTTS) is a relatively uncommon lesion. GCTTS composed largely epithelioid histiocytes are very rare. In the literature, the author could not find such cases. A 73-year-old man presented with a mass of right thumb, and resection of the mass was performed. Grossly, the mass was encapsulated and yellowish, and measured 1.5 x 2 x 2 cm. Microscopically, the mass was composed of cellular and hypocellular zones. The former was composed of spindle cells and osteoclast-like giant cells, while the latter of epithelioid clear histiocytes. The area of the former was 20%, and the latter 80%. Pigment was seen in the former elements. Mitotic figures were seen in 3/per 30 high power fields (HPFs) in the former element and 2/per 30 HPFs in the latter element. Histochemically, the pigment was hemosiderin positive with Prussian blue staining. Immunohistochemically, both the elements were negative for cytokeratin (CK) CE1/3, CK CAM5.2, CEA, HMB45, alpha-smooth muscle antigen, p53, CD10, TTF-1, and CDX2. Both the elements were positive for CD68 and Ki-67 (cellular element 30% and hypocellular element 20%). The histiocytes of the hypocellular element and osteoclast-like giant cell of the cellular element were positive for CD45. S100-protein positive Langerhans cells and CD45-positive lymphocytes were scattered. The pathological diagnosis was GCTTS. In the author's experience, GCTTS composed largely epithelioid histiocytes are very rare. In the literature, the author could not find such cases. Thus, the author reports herein this case. PMID- 22670183 TI - Tumor-to-tumor metastasis: pathology and neuroimaging considerations. AB - The phenomenon of tumor-to-tumor metastasis has been reported in the literature for over a century. However, it remains fairly uncommon, with fewer than 100 cases being described during that time. Virtually any benign or malignant tumor can be a recipient, but meningiomas have been implicated as the most common intracranial neoplasm to harbor metastasis. The donor neoplasm is most frequently lung or breast carcinoma, while rare cases of metastasis from other primary tumors have been reported. We report here three examples of such rare metastases. This case series reports the first documented instance involving rectal adenocarcinoma. In addition, we report two cases of metastatic prostate adenocarcinoma to a meningioma; to date of which only three cases have been published. The terms "tumor-to-tumor metastasis" and "collision tumor" are addressed, as are details of the pathology. The limitations of standard radiological imaging techniques, such as standard CT and MR, which cannot reliably identify the presence of metastasis within a meningioma are compared with physiology-based neuroimaging methods, such as perfusion MR and MR spectroscopy, which may be more useful in noninvasively differentiating tumor histology. PMID- 22670185 TI - Hemophagocytic syndrome secondary to adult-onset Still's disease but very similar to lymphoma. AB - Hemophagocytic syndrome (HPS) is a clinicopathologic entity characterized by increased proliferation and activation of benign macrophages with hemophagocytosis throughout the reticuloendothelial system. HPS may be primary, or secondary to malignancy, infections, auto-immune diseases and pharmacotherapy. In patients with adult-onset Still's disease (AOSD), HPS is a rare but life threatening complication. Herein, we described a female patient with HPS secondary to AOSD. During the therapy, giant gastric ulcer similar to lymphoma developed after treatment with corticosteroid and nonsteroidal anti-inflammatory drugs. PMID- 22670187 TI - High-grade prostatic intraepithelial neoplasia. AB - High-grade prostatic intraepithelial neoplasia (HGPIN) has been established as a precursor to prostatic adenocarcinoma. HGPIN shares many morphological, genetic, and molecular signatures with prostate cancer. Its predictive value for the development of future adenocarcinoma during the prostate-specific antigen screening era has decreased, mostly owing to the increase in prostate biopsy cores. Nevertheless, a literature review supports that large-volume HGPIN and multiple cores of involvement at the initial biopsy should prompt a repeat biopsy of the prostate within 1 year. No treatment is recommended for HGPIN to slow its progression to cancer. PMID- 22670188 TI - Incidence of bladder cancer in sri lanka: analysis of the cancer registry data and review of the incidence of bladder cancer in the South asian population. AB - PURPOSE: To investigate the incidence of bladder cancer (BC) in Sri Lanka and to compare risk factors and outcomes with those of other South Asian nations and South Asian migrants to the United Kingdom (UK) and the United States (US). MATERIALS AND METHODS: The incidence of BC in Sri Lanka was examined by using two separate cancer registry databases over a 5-year period. Smoking rates were compiled by using a population-based survey from 2001 to 2009 and the relative risk was calculated by using published data. RESULTS: A total of 637 new cases of BC were diagnosed over the 5-year period. Sri Lankan BC incidence increased from 1985 but remained low (1.36 and 0.3 per 100,000 in males and females) and was similar to the incidence in other South Asian countries. The incidence was lower, however, than in migrant populations in the US and the UK. In densely populated districts of Sri Lanka, these rates almost doubled. Urothelial carcinoma accounted for 72%. The prevalence of male smokers in Sri Lanka was 39%, whereas Pakistan had higher smoking rates with a 6-fold increase in BC. CONCLUSIONS: Sri Lankan BC incidence was low, similar to other South Asian countries (apart from Pakistan), but the actual incidence is likely higher than the cancer registry rates. Smoking is likely to be the main risk factor for BC. Possible under reporting in rural areas could account for the low rates of BC in Sri Lanka. Any genetic or environmental protective effects of BC in South Asians seem to be lost on migration to the UK or the US and with higher levels of smoking, as seen in Pakistan. PMID- 22670189 TI - Surgical experience with retroperitoneal liposarcoma in a single korean tertiary medical center. AB - PURPOSE: This is a report of the surgical treatment and prognosis of retroperitoneal liposarcoma (RPLS) in Koreans. MATERIALS AND METHODS: Nineteen patients treated for RPLS between July 1, 1984, and March 31, 2009, were included. Patient demographics, histopathologic subtypes, survival rate, disease recurrence rate and interval, and adjuvant therapy were reviewed and analyzed. RESULTS: Of the 19 patients diagnosed with RPLS, 26.3% presented with well differentiated RPLS, 10.5% with dedifferentiated RPLS, 15.8% with myxoid/round cell type, and 47.4% with mixed-type liposarcoma. The mean follow-up period was 66.8 months (range, 6 to 165 months). Primary RPLS was treated in 17 patients. Nine patients (52.9%) had recurrent disease, and recurrence developed at a mean of 47.7 months after primary or repeated surgical treatment. The overall survival rate was 84.2% during a mean follow-up of 66.8 months. The 3- and 5-year survival rates were 86.9%, and the 10-year survival rate was 69.5%. The recurrence interval was significantly shorter in recurrent RPLS cases (p=0.023). The mean growth rate of locally recurrent tumors was 0.34 cm per month. CONCLUSIONS: The survival rates reported here were higher than in previous studies. Locally recurrent tumors presented with a low growth rate, which may have contributed to the relatively high survival rate. A high prevalence of mixed-type RPLS was also noted, and its cause and prognosis require further research. PMID- 22670190 TI - Prognostic Significance of Substaging according to the Depth of Lamina Propria Invasion in Primary T1 Transitional Cell Carcinoma of the Bladder. AB - PURPOSE: To evaluate the prognostic significance of the depth of lamina propria invasion in primary T1 transitional cell carcinoma (TCC) of the bladder. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 183 patients with primary T1 TCC of the bladder who had undergone transurethral resection (TUR) at our institution. Substaging was defined according to the depth of lamina propria invasion as follows: T1a, superficial invasion of lamina propria; T1b, invasion into the muscularis mucosa (MM); T1c, invasion beyond the MM but not to the muscularis propria. The prognostic significance of various clinicopathological variables for recurrence and progression was analyzed. RESULTS: Of the 183 patients, substaging was T1a in 119, T1b in 57, and T1c in 7 patients. The recurrence rate was 32.8% for T1a and 40.6% for T1b/c, but there was no significant difference between the two groups. The progression rate was significantly different between the two groups: 5.8% in T1a and 21.9% in T1b/c (p=0.003). The cancer-specific mortality rate was also significantly different: 4.2% in T1a and 14.0% in T1b/c (p=0.036). In the univariate analysis, microscopic tumor architecture was the only significant prognostic factor for recurrence. In the univariate and multivariate analysis concerning progression, depth of lamina propria invasion and concomitant carcinoma in situ were significant prognostic factors. CONCLUSIONS: Substaging according to the depth of lamina propria invasion in primary T1 TCC of the bladder was an independent prognostic factor for progression. This suggests that substaging would be helpful for guiding decisions about adjuvant therapies and follow-up strategies. PMID- 22670191 TI - Proper mesh placement using the outer cylinder of a ballpoint pen in the transobturator adjustable tape sling procedure for female stress urinary incontinence. AB - PURPOSE: The transobturator adjustable tape (TOA) sling operation is an effective procedure that allows for correction of postoperative incontinence or obstruction through adjustment of the mesh tension. During the operation, the outer cylinder of a ballpoint pen was used for proper mesh placement with less dissection. We evaluated the efficacy and safety of the TOA sling operation with the use of the outer cylinder of a ballpoint pen. MATERIALS AND METHODS: A total of 127 consecutive women with stress urinary incontinence underwent the TOA sling operation with the use of the outer cylinder of a ballpoint pen. The preoperative evaluations included a stress cough test, urodynamic study, and questionnaires related to quality of life. The mesh tension was adjusted 1 day after the operation. Postoperative evaluation was done at 1 month and included a stress cough test, uroflowmetry, questionnaires, and asking about satisfaction. At 1 year, we evaluated the patients with a stress cough test and by asking about their satisfaction with the procedure. RESULTS: The overall cure rate was 95.3% at 1 month and 96.8% at the 1-year follow-up. Postoperative adjustment of the mesh tension was done for 22 patients (17.3%). Eight patients needed increased tension for remaining stress urinary incontinence, and 14 patients needed reduced tension for urinary obstruction. The maximal flow rate was decreased significantly. However, the residual urine volume was not increased significantly. The total score on the questionnaires increased significantly. CONCLUSIONS: Results were excellent compared with outcomes of the traditional TOA sling procedure. Proper mesh placement by use of the outer cylinder of a ballpoint pen with less dissection and tension adjustment could improve the success rate of the TOA sling operation. PMID- 22670192 TI - The Prevalence and Characteristic Differences in Prostatic Calcification between Health Promotion Center and Urology Department Outpatients. AB - PURPOSE: We evaluated the differences in calculi characteristics and their prevalence according to the presence of lower urinary tract symptoms between adult patients examined at the Urology Department and those examined at the Health Promotion Center (HPC). MATERIALS AND METHODS: The prevalence of prostatic calcification, characteristics of calculi (number, size, and location), and differences in lower urinary tract symptoms were compared and analyzed for 479 subjects who underwent transrectal ultrasonography at the HPC and the Urology Outpatients Department at our hospital from October 2009 to October 2010. RESULTS: Of 479 subjects, 268 patients were examined at the HPC, and 211 were examined at the Urology Outpatients Department. Between the two groups, age, prostate-specific antigen levels, prostate volume transrectal ultrasonography, International Prostate Symptom Score (total, voiding, and storage), quality of life, and the prostatic calcification rate were significantly higher in the patients who visited the Urology Outpatients Department. The prevalence of prostatic calcification was 41.5% (199/479), with 36.1% (97/268) from the HPC and 48.3% (102/211) from the Urology Outpatients Department. When the characteristics of prostatic calcification were compared, there were no significant differences in the appearance, size, or location of the calculi between the two groups. CONCLUSIONS: The prevalence of prostatic calcification was high in patients complaining of lower urinary tract symptoms; however, there were no significant differences in the characteristics of the calculi. This finding leads us to believe that prostatic calcification can aggravate lower urinary tract symptoms but does not result in differences according to the number, size, or appearance of the calculi. PMID- 22670193 TI - Is high-sensitivity C-reactive protein associated with lower urinary tract symptoms in aging men? Results from the hallym aging study. AB - PURPOSE: The pathogenesis of lower urinary tract symptoms (LUTS) is uncertain. We investigated the potential role of inflammation in the development of LUTS, with the use of high-sensitivity C-reactive protein (hsCRP) as an inflammatory marker, in a population-based study of aging men in Korea. MATERIALS AND METHODS: Our study used a multistage stratified design to recruit a random sample of 1,510 men aged 45 years or older in Chuncheon, Korea, in 2003. Men with urologic or neurologic diseases that could cause voiding dysfunction were excluded. Also, men with medical conditions that could affect inflammation, such as infection or the use of nonsteroidal anti-inflammatory drugs, were excluded. LUTS were defined according to the International Prostate Symptom Score (IPSS). Various potential confounding factors were included in the analyses. RESULTS: A total of 330 subjects were included in the final analyses. There were 155 (47.0%) with an IPSS<8 and 175 (53%) with an IPSS>=8. The mean age of all subjects was 69.2+/-8.4 years. The mean hsCRP level of all subjects was 2.30+/-3.27 (median, 1.19) mg/l. The hsCRP levels in subjects with an IPSS>=8 differed significantly from those in subjects with an IPSS<8. Also, IPSS, storage symptom, voiding symptom, and quality of life (QoL) scores increased as hsCRP levels increased, respectively. The hsCRP level remained an independent risk factor of LUTS (IPSS>=8, storage symptom score>=4, incomplete voiding, intermittency, and QoL) after adjustment for variable possible confounding factors. CONCLUSIONS: Our results suggest that inflammatory processes may play an important role in the pathogenesis of LUTS and that hsCRP levels may indicate the severity of LUTS in aging men. PMID- 22670194 TI - Prevalence and Clinical Features of Detrusor Underactivity among Elderly with Lower Urinary Tract Symptoms: A Comparison between Men and Women. AB - PURPOSE: To identify the prevalence and clinical features of detrusor underactivity (DU) in elderly men and women presenting with lower urinary tract symptoms (LUTS). MATERIALS AND METHODS: We reviewed 1,179 patients aged over 65 years who had undergone a urodynamic study for LUTS with no neurological or anatomical conditions. DU was defined as a bladder contractility index <100 and a maximal flow rate (Qmax) <=12 ml/s combined with a detrusor pressure at Qmax <=10 cmH(2)O for men and women, respectively. RESULTS: Of the patients, 40.2% of men and 13.3% of women were classified as having DU (p<0.001). Types of clinical symptoms were not significantly different between patients with and without DU. In men, whereas the prevalence of bladder outlet obstruction (BOO) was constant across the age spectrum, the prevalence of DU and detrusor overactivity (DO) increased with age, and 46.5% of men with DU also had DO or BOO. In women, the prevalence of DU also increased with age, and the trend was more remarkable in women aged over 70 years. DU was accompanied by DO or urodynamic stress urinary incontinence (USUI) in 72.6% of the women with DU. Women with DU were found to have lower cystometric capacity and exhibited a greater incidence of reduced compliance than did women without DU. CONCLUSIONS: DU was a common mechanism underlying LUTS in the elderly population, especially in men. One half of the men and three quarters of the women with DU also had other pathologies such as DO, BOO, or USUI. PMID- 22670195 TI - Comparison and efficacy of low-dose and standard-dose tamsulosin and alfuzosin in medical expulsive therapy for lower ureteral calculi: prospective, randomized, comparative study. AB - PURPOSE: Typically in Korea, for a standard dose (0.4 mg) of tamsulosin, two low doses (0.2 mg) are administered. The aim of this study was to evaluate and compare the efficacy of tamsulosin (0.2 mg and 0.4 mg) and alfuzosin (10 mg) in the treatment of lower ureteral stones. MATERIALS AND METHODS: A total of 141 patients presenting with a single 4- to 10-mm sized lower ureteral stone were randomly assigned to 4 groups. Patients in group 1 (n=41) and group 2 (n=30) received an oral dose of 0.2 mg tamsulosin once and twice daily, respectively, and patients in group 3 (n=36) received a daily oral dose of 10 mg alfuzosin. Patients in group 4 (n=34) received trospium chloride only. The spontaneous passage of stones, the stone expulsion time, and adverse effects were evaluated. RESULTS: There were no significant differences in patient background, including age, sex, BMI, stone size, stone side, and symptom duration. The spontaneous stone passage rate through the ureter was higher and the stone expulsion time was faster in groups 1, 2, and 3 than in group 4. There were no statistically different changes in groups 1, 2, and 3. The adverse effects observed in all groups were comparable and were mild. CONCLUSIONS: Tamsulosin at 0.2 mg and 0.4 mg and alfuzosin (10 mg) proved to be safe and effective. A first cycle of medical expulsive therapy with tamsulosin 0.2 mg could be considered as an option in the management of single lower ureteral stone. PMID- 22670196 TI - Long-term urinary bladder function following unilateral refluxing low loop cutaneous ureterostomy. AB - PURPOSE: Unilateral low loop cutaneous ureterostomy (LLCU) has been offered as the preferred method of temporary urinary diversion in cases of massively dilated and refluxing ureters. We sought to explore whether LLCU is effective in preserving urinary bladder function in the long term. MATERIALS AND METHODS: The charts of all patients who had undergone temporary unilateral LLCU as newborns in the presence of massive vesico-ureteric reflux were retrospectively reviewed. Demographic data, follow-up length, and presence of incontinence were recorded. Patients were interviewed regarding lower urinary tract symptoms (LUTS), and their urination patterns were recorded by using uroflow and post-void residual (PVR) measurements. RESULTS: Between 1972 and 2003, a total of 24 patients underwent unilateral LLCU in the presence of massively refluxing ureters. Eight patients were included in the final analysis. The median age at diversion was 12 days, the median time to closure was 22.5 months, and the median follow-up was 12.5 years. Urinary bladders showed normal contour, normal capacities, and minimal PVRs in most cases. None of the patients required augmentation cystoplasty. One patient suffered from urinary leakage and few demonstrated minimal LUTS. CONCLUSIONS: Unilateral refluxing LLCU is an effective method of urinary diversion that preserves urinary bladder function for the long term. Larger studies are required to confirm this finding. PMID- 22670198 TI - Seminal vesicle involvement by urothelial carcinoma in situ of the bladder with mucosal spread pattern: a case report. AB - Mucosal spreading of urothelial tumors to the seminal vesicles is very rare. We experienced a case of mucosal involvement of the seminal vesicles by a bladder tumor in a 72-year-old man. The patient had a history of transurethral resection for invasive urothelial carcinoma of the bladder 8 years previously. Radical cystoprostatectomy was performed owing to recurrent and multiple urothelial carcinoma in situ. Microscopically, the urothelial carcinoma in situ was throughout the mucosa of the urinary bladder, both ureters, the prostate, and the left seminal vesicle. To date, the implication of mucosal involvement of the seminal vesicles by urothelial carcinoma is unclear. However, careful microscopic examination is needed to avoid an erroneous diagnosis. PMID- 22670197 TI - Taxol and taurine protect the renal tissue of rats after unilateral ureteral obstruction: a stereological survey. AB - PURPOSE: Blockage of the urinary tract induces changes in renal structure including tubular dilatation or atrophy, tubular cell death, inflammatory processes, and progressive interstitial fibrosis with the loss of renal parenchyma. The present study was conducted to survey the protective effects of Taxol and taurine on the renal structure after unilateral ureteral obstruction (UUO). MATERIALS AND METHODS: UUO was induced in three groups of rats (n=6) who then received distilled water, Taxol (0.3 mg/kg/d), or taurine (7.5 mg/kg/d). Stereological methods were used to gather quantitative as well as comparative data. RESULTS: Less than -8% of the volume of the glomeruli, proximal convoluted tubules (PCT), distal convoluted tubules (DCT), Henle's loop, and collecting ducts were preserved after UUO. After treatment of the UUO rats with Taxol, between -32% and 88% of the parameters mentioned above remained intact, and after treatment of the UUO rats with taurine, between -16% and 46% of the parameters remained intact (p<0.01). Compared with the untreated UUO animals, the volume of necrotic and fibrotic tissues decreased -53% and -63% in the UUO rats treated with Taxol and taurine, respectively (p<0.01). Less than -3% of the lengths of the renal tubules (PCT, DCT, Henle's loop, and collecting) were preserved in the UUO rats. After treatment with Taxol and taurine, -61% to 70% and -43% to 53% of the length of the renal tubules were preserved, respectively (p<0.01). CONCLUSIONS: Taurine and Taxol are effective in preventing some structural renal damage in a direct ureteral obstruction model. Taxol was more effective in renal protection. PMID- 22670199 TI - Docetaxel-induced fatal interstitial pneumonitis in a patient with castration resistant prostate cancer. AB - A 69-year-old man with castration-resistant prostate cancer (CRPC) received docetaxel and a corticosteroid. After the third cycle of docetaxel administration, he presented with dyspnea, cough, sputum, and fever of 39.2C. The chest X-ray and chest computed tomography (CT) revealed a diffuse reticulonodular shadow in both lungs, which suggested interstitial pneumonitis. Initially, we used empiric broad-spectrum antibiotics and high-dose corticosteroids. However, his condition progressively became worse and he was transferred to the intensive care unit, intubated, and placed on mechanical ventilation. He died 4 days after hospital admission. Here we report this case of fatal interstitial pneumonitis after treatment with docetaxel for CRPC. We briefly consider docetaxel-induced pneumonitis to make physicians aware of the possibility of pulmonary toxicity so that appropriate treatment can be begun as soon as possible. PMID- 22670200 TI - Patient-specific modelling of whole heart anatomy, dynamics and haemodynamics from four-dimensional cardiac CT images. AB - There is a growing need for patient-specific and holistic modelling of the heart to support comprehensive disease assessment and intervention planning as well as prediction of therapeutic outcomes. We propose a patient-specific model of the whole human heart, which integrates morphology, dynamics and haemodynamic parameters at the organ level. The modelled cardiac structures are robustly estimated from four-dimensional cardiac computed tomography (CT), including all four chambers and valves as well as the ascending aorta and pulmonary artery. The patient-specific geometry serves as an input to a three-dimensional Navier-Stokes solver that derives realistic haemodynamics, constrained by the local anatomy, along the entire heart cycle. We evaluated our framework with various heart pathologies and the results correlate with relevant literature reports. PMID- 22670201 TI - Boundary conditions of patient-specific fluid dynamics modelling of cavopulmonary connections: possible adaptation of pulmonary resistances results in a critical issue for a virtual surgical planning. AB - Cavopulmonary connections are surgical procedures used to treat a variety of complex congenital cardiac defects. Virtual pre-operative planning based on in silico patient-specific modelling might become a powerful tool in the surgical decision-making process. For this purpose, three-dimensional models can be easily developed from medical imaging data to investigate individual haemodynamics. However, the definition of patient-specific boundary conditions is still a crucial issue. The present study describes an approach to evaluate the vascular impedance of the right and left lungs on the basis of pre-operative clinical data and numerical simulations. Computational fluid dynamics techniques are applied to a patient with a bidirectional cavopulmonary anastomosis, who later underwent a total cavopulmonary connection (TCPC). Multi-scale models describing the surgical region and the lungs are adopted, while the flow rates measured in the venae cavae are used at the model inlets. Pre-operative and post-operative conditions are investigated; namely, TCPC haemodynamics, which are predicted using patient specific pre-operative boundary conditions, indicates that the pre-operative balanced lung resistances are not compatible with the TCPC measured flows, suggesting that the pulmonary vascular impedances changed individually after the surgery. These modifications might be the consequence of adaptation to the altered pulmonary blood flows. PMID- 22670202 TI - @neurIST complex information processing toolchain for the integrated management of cerebral aneurysms. AB - Cerebral aneurysms are a multi-factorial disease with severe consequences. A core part of the European project @neurIST was the physical characterization of aneurysms to find candidate risk factors associated with aneurysm rupture. The project investigated measures based on morphological, haemodynamic and aneurysm wall structure analyses for more than 300 cases of ruptured and unruptured aneurysms, extracting descriptors suitable for statistical studies. This paper deals with the unique challenges associated with this task, and the implemented solutions. The consistency of results required by the subsequent statistical analyses, given the heterogeneous image data sources and multiple human operators, was met by a highly automated toolchain combined with training. A testimonial of the successful automation is the positive evaluation of the toolchain by over 260 clinicians during various hands-on workshops. The specification of the analyses required thorough investigations of modelling and processing choices, discussed in a detailed analysis protocol. Finally, an abstract data model governing the management of the simulation-related data provides a framework for data provenance and supports future use of data and toolchain. This is achieved by enabling the easy modification of the modelling approaches and solution details through abstract problem descriptions, removing the need of repetition of manual processing work. PMID- 22670203 TI - Computational modelling and evaluation of cardiovascular response under pulsatile impeller pump support. AB - This study presents a numerical simulation of cardiovascular response in the heart failure condition under the support of a Berlin Heart INCOR impeller pump type ventricular assist device (VAD). The model is implemented using the CellML modelling language. To investigate the potential of using the Berlin Heart INCOR impeller pump to produce physiologically meaningful arterial pulse pressure within the various physiological constraints, a series of VAD-assisted cardiovascular cases are studied, in which the pulsation ratio and the phase shift of the VAD motion profile are systematically changed to observe the cardiovascular responses in each of the studied cases. An optimization process is proposed, including the introduction of a cost function to balance the importance of the characteristic cardiovascular variables. Based on this cost function it is found that a pulsation ratio of 0.35 combined with a phase shift of 200 degrees produces the optimal cardiovascular response, giving rise to a maximal arterial pulse pressure of 12.6 mm Hg without inducing regurgitant pump flow while keeping other characteristic cardiovascular variables within appropriate physiological ranges. PMID- 22670204 TI - Influence of different computational approaches for stent deployment on cerebral aneurysm haemodynamics. AB - Cerebral aneurysms are abnormal focal dilatations of artery walls. The interest in virtual tools to help clinicians to value the effectiveness of different procedures for cerebral aneurysm treatment is constantly growing. This study is focused on the analysis of the influence of different stent deployment approaches on intra-aneurysmal haemodynamics using computational fluid dynamics (CFD). A self-expanding stent was deployed in an idealized aneurysmatic cerebral vessel in two initial positions. Different cases characterized by a progression of simplifications on stent modelling (geometry and material) and vessel material properties were set up, using finite element and fast virtual stenting methods. Then, CFD analysis was performed for untreated and stented vessels. Haemodynamic parameters were analysed qualitatively and quantitatively, comparing the cases and the two initial positions. All the cases predicted a reduction of average wall shear stress and average velocity of almost 50 per cent after stent deployment for both initial positions. Results highlighted that, although some differences in calculated parameters existed across the cases based on the modelling simplifications, all the approaches described the most important effects on intra-aneurysmal haemodynamics. Hence, simpler and faster modelling approaches could be included in clinical workflow and, despite the adopted simplifications, support clinicians in the treatment planning. PMID- 22670206 TI - Multi-scale simulations of the dynamics of in-stent restenosis: impact of stent deployment and design. AB - Neointimal hyperplasia, a process of smooth muscle cell re-growth, is the result of a natural wound healing response of the injured artery after stent deployment. Excessive neointimal hyperplasia following coronary artery stenting results in in stent restenosis (ISR). Regardless of recent developments in the field of coronary stent design, ISR remains a significant complication of this interventional therapy. The influence of stent design parameters such as strut thickness, shape and the depth of strut deployment within the vessel wall on the severity of restenosis has already been highlighted but the detail of this influence is unclear. These factors impact on local haemodynamics and vessel structure and affect the rate of neointima formation. This paper presents the first results of a multi-scale model of ISR. The development of the simulated restenosis as a function of stent deployment depth is compared with an in vivo porcine dataset. Moreover, the influence of strut size and shape is investigated, and the effect of a drug released at the site of injury, by means of a drug eluting stent, is also examined. A strong correlation between strut thickness and the rate of smooth muscle cell proliferation has been observed. Simulation results also suggest that the growth of the restenotic lesion is strongly dependent on the stent strut cross-sectional profile. PMID- 22670207 TI - Visualization and simulated surgery of the left ventricle in the virtual pathological heart of the Virtual Physiological Human. AB - Ischaemic heart failure remains a significant health and economic problem worldwide. This paper presents a user-friendly software system that will form a part of the virtual pathological heart of the Virtual Physiological Human (VPH2) project, currently being developed under the European Commission Virtual Physiological Human (VPH) programme. VPH2 is an integrated medicine project, which will create a suite of modelling, simulation and visualization tools for patient-specific prediction and planning in cases of post-ischaemic left ventricular dysfunction. The work presented here describes a three-dimensional interactive visualization for simulating left ventricle restoration surgery, comprising the operations of cutting, stitching and patching, and for simulating the elastic deformation of the ventricle to its post-operative shape. This will supply the quantitative measurements required for the post-operative prediction tools being developed in parallel in the same project. PMID- 22670205 TI - euHeart: personalized and integrated cardiac care using patient-specific cardiovascular modelling. AB - The loss of cardiac pump function accounts for a significant increase in both mortality and morbidity in Western society, where there is currently a one in four lifetime risk, and costs associated with acute and long-term hospital treatments are accelerating. The significance of cardiac disease has motivated the application of state-of-the-art clinical imaging techniques and functional signal analysis to aid diagnosis and clinical planning. Measurements of cardiac function currently provide high-resolution datasets for characterizing cardiac patients. However, the clinical practice of using population-based metrics derived from separate image or signal-based datasets often indicates contradictory treatments plans owing to inter-individual variability in pathophysiology. To address this issue, the goal of our work, demonstrated in this study through four specific clinical applications, is to integrate multiple types of functional data into a consistent framework using multi-scale computational modelling. PMID- 22670208 TI - Left ventricular modelling: a quantitative functional assessment tool based on cardiac magnetic resonance imaging. AB - We present the development and testing of a semi-automated tool to support the diagnosis of left ventricle (LV) dysfunctions from cardiac magnetic resonance (CMR). CMR short-axis images of the LVs were obtained in 15 patients and processed to detect endocardial and epicardial contours and compute volume, mass and regional wall motion (WM). Results were compared with those obtained from manual tracing by an expert cardiologist. Nearest neighbour tracking and finite element theory were merged to calculate local myocardial strains and torsion. The method was tested on a virtual phantom, on a healthy LV and on two ischaemic LVs with different severity of the pathology. Automated analysis of CMR data was feasible in 13/15 patients: computed LV volumes and wall mass correlated well with manually extracted data. The detection of regional WM abnormalities showed good sensitivity (77.8%), specificity (85.1%) and accuracy (82%). On the virtual phantom, computed local strains differed by less than 14 per cent from the results of commercial finite-element solver. Strain calculation on the healthy LV showed uniform and synchronized circumferential strains, with peak shortening of about 20 per cent at end systole, progressively higher systolic wall thickening going from base to apex, and a 10 degrees torsion. In the two pathological LVs, synchronicity and homogeneity were partially lost, anomalies being more evident for the more severely injured LV. Moreover, LV torsion was dramatically reduced. Preliminary testing confirmed the validity of our approach, which allowed for the fast analysis of LV function, even though future improvements are possible. PMID- 22670209 TI - Coupled personalization of cardiac electrophysiology models for prediction of ischaemic ventricular tachycardia. AB - In order to translate the important progress in cardiac electrophysiology modelling of the last decades into clinical applications, there is a requirement to make macroscopic models that can be used for the planning and performance of the clinical procedures. This requires model personalization, i.e. estimation of patient-specific model parameters and computations compatible with clinical constraints. Simplified macroscopic models can allow a rapid estimation of the tissue conductivity, but are often unreliable to predict arrhythmias. Conversely, complex biophysical models are more complete and have mechanisms of arrhythmogenesis and arrhythmia sustainibility, but are computationally expensive and their predictions at the organ scale still have to be validated. We present a coupled personalization framework that combines the power of the two kinds of models while keeping the computational complexity tractable. A simple eikonal model is used to estimate the conductivity parameters, which are then used to set the parameters of a biophysical model, the Mitchell-Schaeffer (MS) model. Additional parameters related to action potential duration restitution curves for the tissue are further estimated for the MS model. This framework is applied to a clinical dataset derived from a hybrid X-ray/magnetic resonance imaging and non contact mapping procedure on a patient with heart failure. This personalized MS model is then used to perform an in silico simulation of a ventricular tachycardia (VT) stimulation protocol to predict the induction of VT. This proof of concept opens up possibilities of using VT induction modelling in order to both assess the risk of VT for a given patient and also to plan a potential subsequent radio-frequency ablation strategy to treat VT. PMID- 22670210 TI - A tool for multi-scale modelling of the renal nephron. AB - We present the development of a tool, which provides users with the ability to visualize and interact with a comprehensive description of a multi-scale model of the renal nephron. A one-dimensional anatomical model of the nephron has been created and is used for visualization and modelling of tubule transport in various nephron anatomical segments. Mathematical models of nephron segments are embedded in the one-dimensional model. At the cellular level, these segment models use models encoded in CellML to describe cellular and subcellular transport kinetics. A web-based presentation environment has been developed that allows the user to visualize and navigate through the multi-scale nephron model, including simulation results, at the different spatial scales encompassed by the model description. The Zinc extension to Firefox is used to provide an interactive three-dimensional view of the tubule model and the native Firefox rendering of scalable vector graphics is used to present schematic diagrams for cellular and subcellular scale models. The model viewer is embedded in a web page that dynamically presents content based on user input. For example, when viewing the whole nephron model, the user might be presented with information on the various embedded segment models as they select them in the three-dimensional model view. Alternatively, the user chooses to focus the model viewer on a cellular model located in a particular nephron segment in order to view the various membrane transport proteins. Selecting a specific protein may then present the user with a description of the mathematical model governing the behaviour of that protein-including the mathematical model itself and various simulation experiments used to validate the model against the literature. PMID- 22670211 TI - On the formalization of multi-scale and multi-science processes for integrative biology. AB - The aim of this work is to introduce the general concept of 'Bond Graph' (BG) techniques applied in the context of multi-physics and multi-scale processes. BG modelling has a natural place in these developments. BGs are inherently coherent as the relationships defined between the 'elements' of the graph are strictly defined by causality rules and power (energy) conservation. BGs clearly show how power flows between components of the systems they represent. The 'effort' and 'flow' variables enable bidirectional information flow in the BG model. When the power level of a system is low, BGs degenerate into signal flow graphs in which information is mainly one-dimensional and power is minimal, i.e. they find a natural limitation when dealing with populations of individuals or purely kinetic models, as the concept of energy conservation in these systems is no longer relevant. The aim of this work is twofold: on the one hand, we will introduce the general concept of BG techniques applied in the context of multi-science and multi-scale models and, on the other hand, we will highlight some of the most promising features in the BG methodology by comparing with examples developed using well-established modelling techniques/software that could suggest developments or refinements to the current state-of-the-art tools, by providing a consistent framework from a structural and energetic point of view. PMID- 22670212 TI - Workflow for generating competing hypothesis from models with parameter uncertainty. AB - Mathematical models are increasingly used in life sciences. However, contrary to other disciplines, biological models are typically over-parametrized and loosely constrained by scarce experimental data and prior knowledge. Recent efforts on analysis of complex models have focused on isolated aspects without considering an integrated approach-ranging from model building to derivation of predictive experiments and refutation or validation of robust model behaviours. Here, we develop such an integrative workflow, a sequence of actions expanding upon current efforts with the purpose of setting the stage for a methodology facilitating an extraction of core behaviours and competing mechanistic hypothesis residing within underdetermined models. To this end, we make use of optimization search algorithms, statistical (machine-learning) classification techniques and cluster-based analysis of the state variables' dynamics and their corresponding parameter sets. We apply the workflow to a mathematical model of fat accumulation in the arterial wall (atherogenesis), a complex phenomena with limited quantitative understanding, thus leading to a model plagued with inherent uncertainty. We find that the mathematical atherogenesis model can still be understood in terms of a few key behaviours despite the large number of parameters. This result enabled us to derive distinct mechanistic predictions from the model despite the lack of confidence in the model parameters. We conclude that building integrative workflows enable investigators to embrace modelling of complex biological processes despite uncertainty in parameters. PMID- 22670213 TI - Clinically driven design of multi-scale cancer models: the ContraCancrum project paradigm. AB - The challenge of modelling cancer presents a major opportunity to improve our ability to reduce mortality from malignant neoplasms, improve treatments and meet the demands associated with the individualization of care needs. This is the central motivation behind the ContraCancrum project. By developing integrated multi-scale cancer models, ContraCancrum is expected to contribute to the advancement of in silico oncology through the optimization of cancer treatment in the patient-individualized context by simulating the response to various therapeutic regimens. The aim of the present paper is to describe a novel paradigm for designing clinically driven multi-scale cancer modelling by bringing together basic science and information technology modules. In addition, the integration of the multi-scale tumour modelling components has led to novel concepts of personalized clinical decision support in the context of predictive oncology, as is also discussed in the paper. Since clinical adaptation is an inelastic prerequisite, a long-term clinical adaptation procedure of the models has been initiated for two tumour types, namely non-small cell lung cancer and glioblastoma multiforme; its current status is briefly summarized. PMID- 22670214 TI - Audited credential delegation: a usable security solution for the virtual physiological human toolkit. AB - We present applications of audited credential delegation (ACD), a usable security solution for authentication, authorization and auditing in distributed virtual physiological human (VPH) project environments that removes the use of digital certificates from end-users' experience. Current security solutions are based on public key infrastructure (PKI). While PKI offers strong security for VPH projects, it suffers from serious usability shortcomings in terms of end-user acquisition and management of credentials which deter scientists from exploiting distributed VPH environments. By contrast, ACD supports the use of local credentials. Currently, a local ACD username-password combination can be used to access grid-based resources while Shibboleth support is underway. Moreover, ACD provides seamless and secure access to shared patient data, tools and infrastructure, thus supporting the provision of personalized medicine for patients, scientists and clinicians participating in e-health projects from a local to the widest international scale. PMID- 22670215 TI - Drug transporters in spermatogenesis: A re-evaluation of recent data on P glycoprotein. AB - Drug transporters are integral membrane proteins expressed by a variety of organs, including the liver, kidney, small intestine and testis, and they are generally known to mediate drug or xenobiotic transport into and out of cells. Previous studies have also reported the presence of several drug transporters at blood-tissue barriers where they are thought to protect organs from harmful agents. In this editorial, we briefly discuss and re-evaluate recent findings that show P-glycoprotein, an efflux pump, to function at the blood-testis barrier. We also put forth a mechanistic model, hoping this information will form a strong basis for future studies. PMID- 22670216 TI - Filamin A: A regulator of blood-testis barrier assembly during post-natal development. AB - Filamins are a family of actin-binding proteins composed of filamin A, B and C. Besides of their ability to induce perpendicular branching of F-actin filaments via their actin binding domains near the N-terminus, filamins can regulate multiple cellular functions because of their unique ability to recruit more than 90 protein binding partners to their primary sequences which are having highly diversified cellular functions. However, this family of proteins has not been examined in the testis until recently. Herein, we highlight recent findings in the field regarding the role of these proteins in cell epithelia, and based on recent data in the testis regarding their role on spermatogenesis, this review provides the basis for future functional studies. PMID- 22670217 TI - Peritubular myoid cells have a role in postnatal testicular growth. AB - FSH stimulates testicular growth by increasing Sertoli cell proliferation and elongation of seminiferous cords. Little is known about the peritubular myoid cells in testicular development. In order to investigate the role of peritubular myoid cells in early testicular growth in rodents, two traditional models to induce testicular growth were used: FSH treatment and hemicastration. In order to affect proliferation of peritubular myoid cells, both treatments were combined with imatinib, a tyrosine kinase inhibitor. In addition, effects of imatinib on human testicular peritubular cell proliferation were investigated. Testicular weight, diameter and length of seminiferous cords, numbers of germ, Sertoli and BrdU-positive cells and FSH-levels were measured. FSH treatment and hemicastration increased length of the seminiferous cords and testicular weight by increasing first the early proliferation of peritubular myoid cells and later also the proliferation of the Sertoli cells. Imatinib blocked the FSH and hemicastration -induced testicular hypertrophy and decreased the proliferation of PDGF-stimulated human testicular peritubular cells in vitro. Present results provide new evidence that peritubular myoid cells have an important role in postnatal testicular growth. PMID- 22670218 TI - Daily sperm production and evaluation of morphological reproductive parameters of Murrah buffaloes in an extensive breeding system. AB - The development of male sexual maturity varies among buffaloes. The Murrah buffalo is considered the most important and efficient milk and fat producer, but aspects of its reproductive biology are still unknown. The present study aimed to evaluate the daily sperm production (DSP) and spermatogenesis in developing Murrah buffalo bulls by evaluation of the seminiferous tubules, testicular morphometry and using light microscopy and scanning electron microscopy. The testes of Murrah buffalo bulls at 18 mo was immature and at 24 mo could still be considered an average-efficiency breed based on their DSP. At 24 mo, the DSP rate was 0.97 billion sperm per testis and 13 million sperm per gram of testis. However, the animals had superior morphometric parameters compared with those of other livestock animals, except for the seminiferous tubule volume and diameter, which were inferior. In conclusion, our data support former views that the testes of the Murrah breed does not reach sexual maturity before 2 y of age and that important developmental steps occur later than Murrah crossbreeds from Brazil. PMID- 22670219 TI - Ontogenic development of spermatids during spermiogenesis in the high altitude bunchgrass lizard (Sceloporus bicanthalis). AB - The body of ultrastructural data on spermatid characters during spermiogenesis continues to grow in reptiles, but is still relatively limited within the squamates. This study focuses on the ontogenic events of spermiogenesis within a viviparous and continually spermatogenic lizard, from high altitude in Mexico. Between the months of June and August, testicular tissues were collected from eight spermatogenically active bunchgrass lizards (Sceloporus bicanthalis) from Nevado de Toluca, Mexico. The testicular tissues were processed for transmission electron microscopy and analyzed to access the ultrastructural differences between spermatid generations during spermiogenesis. Interestingly, few differences exist between S. bicanthalis spermiogenesis when compared with what has been described for other saurian squamates. Degrading and coiling membrane structures similar to myelin figures were visible within the developing acrosome that are likely remnants from Golgi body vesicles. During spermiogenesis, an electron lucent area between the subacrosomal space and the acrosomal medulla was observed, which has been observed in other squamates but not accurately described. Thus, we elect to term this region the acrosomal lucent ridge. This study furthers the existing knowledge of spermatid development in squamates, which could be useful in future work on the reproductive systems in high altitude viviparous lizard species. PMID- 22670220 TI - Age-dependent alterations in spermatogenesis in itchy mice. AB - Spermatogenesis is an intricate process in which spermatogonial stem cells divide and differentiate to produce mature sperm. This process strongly depends on protein turnover both in the developing germ cells and the supportive Sertoli cells, and recent evidence has demonstrated the role of the ubiquitin-proteasome system in this protein turnover in the testis. Itch, an E3 ligase important in the immune system, has been implicated in regulating the blood testis barrier. Although the specific role of Itch during spermatogenesis is not yet well understood, its ubiquitous expression and wide array of functional targets suggest multiple and tissue-specific roles. Here the testes of mice that lack Itch protein are evaluated at two developmental time points: peri-pubertal postnatal day (PND) 28 and adult PND 56. Itchy mice demonstrate an increased germ cell apoptotic index compared with wild type C57BL/6J mice at both PND 28 and PND 56. A corresponding 27% reduction in the total number of spermatid heads produced in PND 56 itchy mice was also evident. A histological evaluation of itchy mice revealed a delay in spermatogenesis at PND 28 and disorganization of late stage spermatids at PND 56. An analysis of several apoptotic markers revealed an age dependent change in cleaved caspase 9, an intrinsic apoptosis mediator. The breeding success of the itchy mice was also significantly decreased, possibly due to a developmental defect. Taken together, these findings indicate that Itch is required for functional spermatogenesis, and that it may play differing cellular roles during development. PMID- 22670221 TI - Microtubule affinity-regulating kinase 4 (MARK4) is a component of the ectoplasmic specialization in the rat testis. AB - During the seminiferous epithelial cycle of spermatogenesis, the ectoplasmic specialization (ES, a testis-specific adherens junction, AJ, type) maintains the polarity of elongating/elongated spermatids and confers adhesion to Sertoli cells in the seminiferous epithelium, and known as the apical ES. On the other hand, the ES is also found at the Sertoli-Sertoli cell interface at the blood-testis barrier (BTB) known as basal ES, which together with the tight junction (TJ), maintains Sertoli cell polarity and adhesion, creating a functional barrier that limits paracellular transport of substances across the BTB. However, the apical and basal ES are segregated and restricted to the adluminal compartment and the BTB, respectively. During the transit of preleptotene spermatocytes across the BTB and the release of sperm at spermiation at stage VIII of the seminiferous epithelial cycle, both the apical and basal ES undergo extensive restructuring to facilitate cell movement at these sites. The regulation of these events, in particular their coordination, remains unclear. Studies in other epithelia have shown that the tubulin cytoskeleton is intimately related to cell movement, and MARK [microtubule-associated protein (MAP)/microtubule affinity-regulating kinase] family kinases are crucial regulators of tubulin cytoskeleton stability. Herein MARK4, the predominant member of the MARK protein family in the testis, was shown to be expressed by both Sertoli and germ cells. MARK4 was also detected at the apical and basal ES, displaying highly restrictive spatiotemporal expression at these sites, as well as co-localizing with markers of the apical and basal ES. The expression of MARK4 was found to be stage-specific during the epithelial cycle, structurally associating with alpha-tubulin and the desmosomal adaptor plakophilin-2, but not with actin-based BTB proteins occludin, beta catenin and Eps8 (epidermal growth factor receptor pathway substrate 8, an actin bundling and barbed end capping protein). More importantly, it was shown that the expression of MARK4 tightly associated with the integrity of the apical ES because a diminished expression of MARK4 associated with apical ES disruption that led to the detachment of elongating/elongated spermatids from the epithelium. These findings thus illustrate that the integrity of apical ES, an actin-based and testis-specific AJ, is dependent not only on the actin filament network, but also on the tubulin-based cytoskeleton. PMID- 22670222 TI - New and Redesigned pRS Plasmid Shuttle Vectors for Genetic Manipulation of Saccharomycescerevisiae. AB - We have constructed a set of 42 plasmid shuttle vectors based on the widely used pRS series for use in the budding yeast Saccharomyces cerevisiae and the bacterium Escherichia coli. This set of pRSII plasmids includes new shuttle vectors that can be used with histidine and adenine auxotrophic laboratory yeast strains carrying mutations in the genes HIS2 and ADE1, respectively. Our pRSII plasmids also include updated versions of commonly used pRS plasmids from which common restriction sites that occur within their yeast-selectable biosynthetic marker genes have been removed to increase the availability of unique restriction sites within their polylinker regions. Hence, our pRSII plasmids are a complete set of integrating, centromere and 2MU episomal plasmids with the biosynthetic marker genes ADE2, HIS3, TRP1, LEU2, URA3, HIS2, and ADE1 and a standardized selection of at least 16 unique restriction sites in their polylinkers. Additionally, we have expanded the range of drug selection options that can be used for PCR-mediated homologous replacement using pRS plasmid templates by replacing the G418-resistance kanMX4 cassette of pRS400 with MX4 cassettes encoding resistance to phleomycin, hygromycin B, nourseothricin, and bialaphos. Finally, in the process of generating the new plasmids, we have determined several errors in existing publicly available sequences for several commonly used yeast plasmids. Using our updated sequences, we constructed pRS plasmid backbones with a unique restriction site for inserting new markers to facilitate future expansion of the pRS series. PMID- 22670223 TI - Genetics of ascites resistance and tolerance in chicken: a random regression approach. AB - Resistance and tolerance are two complementary mechanisms to reduce the detrimental effects of parasites, pathogens, and production diseases on host performance. Using body weight and ascites data on domesticated chicken Gallus gallus domesticus, we demonstrate the use of random regression animal model and covariance functions to estimate genetic parameters for ascites resistance and tolerance and illustrate the way individual variation in resistance and tolerance induce both genotype re-ranking and changes in variation of host performance along increasing ascites severity. Tolerance to ascites displayed significant genetic variance, with the estimated breeding values of tolerance slope ranging from strongly negative (very sensitive genotype) to weakly negative (less sensitive). Resistance to ascites had heritability of 0.34. Both traits are hence expected to respond to selection. The two complementary defense strategies, tolerance and resistance, were genetically independent. Ascites induced changes to the correlations between ascites resistance and body weight, with the genetic correlations being weak when birds were ascites-free but moderately negative when both healthy and affected birds were present. This likely results because ascites reduces growth, and thus high ascites incidence is genetically related to low adult body weight. Although ascites induced elevated phenotypic and genetic variances in body weight of affected birds, heritability displayed negligible changes across healthy and affected birds. Ascites induced moderate genotype re ranking in body weight, with the genetic correlation of healthy birds with mildly affected birds being unity but with severely affected birds 0.45. This study demonstrates a novel approach for exploring genetics of defense traits and their impact on genotype-by-environment interactions. PMID- 22670224 TI - Two-phase analysis in consensus genetic mapping. AB - Numerous mapping projects conducted on different species have generated an abundance of mapping data. Consequently, many multilocus maps have been constructed using diverse mapping populations and marker sets for the same organism. The quality of maps varies broadly among populations, marker sets, and software used, necessitating efforts to integrate the mapping information and generate consensus maps. The problem of consensus genetic mapping (MCGM) is by far more challenging compared with genetic mapping based on a single dataset, which by itself is also cumbersome. The additional complications introduced by consensus analysis include inter-population differences in recombination rate and exchange distribution along chromosomes; variations in dominance of the employed markers; and use of different subsets of markers in different labs. Hence, it is necessary to handle arbitrary patterns of shared sets of markers and different level of mapping data quality. In this article, we introduce a two-phase approach for solving MCGM. In phase 1, for each dataset, multilocus ordering is performed combined with iterative jackknife resampling to evaluate the stability of marker orders. In this phase, the ordering problem is reduced to the well-known traveling salesperson problem (TSP). Namely, for each dataset, we look for order that gives minimum sum of recombination distances between adjacent markers. In phase 2, the optimal consensus order of shared markers is selected from the set of allowed orders and gives the minimal sum of total lengths of nonconflicting maps of the chromosome. This criterion may be used in different modifications to take into account the variation in quality of the original data (population size, marker quality, etc.). In the foregoing formulation, consensus mapping is considered as a specific version of TSP that can be referred to as "synchronized TSP." The conflicts detected after phase 1 are resolved using either a heuristic algorithm over the entire chromosome or an exact/heuristic algorithm applied subsequently to the revealed small non-overlapping regions with conflicts separated by non-conflicting regions. The proposed approach was tested on a wide range of simulated data and real datasets from maize. PMID- 22670225 TI - Simplified Insertion of Transgenes Onto Balancer Chromosomes via Recombinase Mediated Cassette Exchange. AB - Balancer chromosomes are critical tools for Drosophila genetics. Many useful transgenes are inserted onto balancers using a random and inefficient process. Here we describe balancer chromosomes that can be directly targeted with transgenes of interest via recombinase-mediated cassette exchange (RMCE). PMID- 22670226 TI - Identification of Mutant Versions of the Spt16 Histone Chaperone That Are Defective for Transcription-Coupled Nucleosome Occupancy in Saccharomyces cerevisiae. AB - The highly conserved FACT (Facilitates Chromatin Transactions) complex performs essential functions in eukaryotic cells through the reorganization of nucleosomes. During transcription, FACT reorganizes nucleosomes to allow passage of RNA Polymerase II and then assists in restoring these nucleosomes after RNA Polymerase II has passed. We have previously shown, consistent with this function, that Spt16 facilitates repression of the Saccharomyces cerevisiae SER3 gene by maintaining nucleosome occupancy over the promoter of this gene as a consequence of intergenic transcription of SRG1 noncoding DNA. In this study, we report the results of a genetic screen to identify mutations in SPT16 that derepress SER3. Twenty-five spt16 mutant alleles were found to derepress SER3 without causing significant reductions in either SRG1 RNA levels or Spt16 protein levels. Additional phenotypic assays indicate that these mutants have general transcription defects related to altered chromatin structure. Our analyses of a subset of these spt16 mutants reveal defects in SRG1 transcription-coupled nucleosome occupancy over the SER3 promoter. We provide evidence that these mutants broadly impair transcription-coupled nucleosome occupancy at highly transcribed genes but not at lowly transcribed genes. Finally, we show that one consequence shared by these mutations is the reduced binding of mutant Spt16 proteins across SRG1 and other highly transcribed genes. Taken together, our results highlight an important role for Spt16 in orchestrating transcription coupled nucleosome assembly at highly transcribed regions of the genome, possibly by facilitating the association of Spt16 during this process. PMID- 22670227 TI - Regulated Expression of Chromobox Homolog 5 Revealed in Tumors of Apc(Min) (/+) ROSA11 Gene Trap Mice. AB - The gene-trap lacZ reporter insertion, ROSA11, in the Cbx5 mouse gene illuminates the regulatory complexity of this locus in Apc(Min) (/+) mice. The insertion site of the beta-Geo gene-trap element lies in the 24-kb intron proximal to the coding region of Cbx5. Transcript analysis indicates that two promoters for Cbx5 flank this insertion site. Heterozygotes for the insertion express lacZ widely in fetal tissues but show limited expression in adult tissues. In the intestine, strong expression is limited to proliferative zones of crypts and tumors. Homozygotes for ROSA11, found at a lower than Mendelian frequency, express reduced levels of the coding region transcript in normal tissues, using a downstream promoter. Analysis via real-time polymerase chain reaction indicates that the upstream promoter is the dominant promoter in normal epithelium and tumors. Bioinformatic analysis of the Cbx5 locus indicates that WNT and its target transcription factor MYC can establish a feedback loop that may play a role in regulating the self renewal of the normal intestinal epithelium and its tumors. PMID- 22670228 TI - Multienvironment quantitative trait Loci analysis for photosynthate acquisition, accumulation, and remobilization traits in common bean under drought stress. AB - Many of the world's common bean (Phaseolus vulgaris L.) growing regions are prone to either intermittent or terminal drought stress, making drought the primary cause of yield loss under farmers' field conditions. Improved photosynthate acquisition, accumulation, and then remobilization have been observed as important mechanisms for adaptation to drought stress. The objective of this study was to tag quantitative trait loci (QTL) for photosynthate acquisition, accumulation, and remobilization to grain by using a recombinant inbred line population developed from the Mesoamerican intragenepool cross of drought susceptible DOR364 and drought-tolerant BAT477 grown under eight environments differing in drought stress across two continents: Africa and South America. The recombinant inbred line population expressed quantitative variation and transgressive segregation for 11 traits associated with drought tolerance. QTL were detected by both a mixed multienvironment model and by composite interval mapping for each environment using a linkage map constructed with 165 genetic markers that covered 11 linkage groups of the common bean genome. In the multienvironment, mixed model, nine QTL were detected for 10 drought stress tolerance mechanism traits found on six of the 11 linkage groups. Significant QTL * environment interaction was observed for six of the nine QTL. QTL * environment interaction was of the cross-over type for three of the six significant QTL with contrasting effect of the parental alleles across different environments. In the composite interval mapping, we found 69 QTL in total. The majority of these were found for Palmira (47) or Awassa (18), with fewer in Malawi (4). Phenotypic variation explained by QTL in single environments ranged up to 37%, and the most consistent QTL were for Soil Plant Analysis Development (SPAD) leaf chlorophyll reading and pod partitioning traits. QTL alignment between the two detection methods showed that yield QTL on b08 and stem carbohydrate QTL on b05 were most consistent between the multilocation model and the single environment detection. Our results indicate the relevance of QTL detection in the sites in which bean breeding will be undertaken and the importance of photosynthate accumulation as a trait for common bean drought tolerance. PMID- 22670229 TI - Aging Uncouples Heritability and Expression-QTL in Caenorhabditis elegans. AB - The number and distribution of gene expression QTL (eQTL) represent the genetic architecture of many complex traits, including common human diseases. We previously reported that the heritable eQTL patterns are highly dynamic with age in an N2 * CB4856 recombinant inbred population of the nematode Caenorhabditis elegans. In particular, we showed that the number of eQTL decreased with age. Here, we investigated the reason for this decrease by combining gene expression profiles at three ages in the wild types N2 and CB4856 with the reported expression profiles of the RIL population. We determined heritability and transgression (when gene expression levels in the RILs are more extreme than the parents) and investigated their relation with eQTL changes with age. Transgressive segregation was widespread but depended on physiological age. The percentage of genes with an eQTL increased with a higher heritability in young worms. However, for old worms this percentage hardly increased. Using a single marker approach, we found that almost 20% of genes with heritability >0.9 had an eQTL in developing worms. Surprisingly, only 10% was found in old worms. Using a multimarker approach, this percentage increased to almost 30% for both age groups. Comparison of the single marker to a multiple marker eQTL mapping indicated that heritable regulation of gene expression becomes more polygenic in aging worms due to multiple loci and possible epistatic interactions. We conclude that linkage studies should account for the relation between increased polygenic regulation and diminished effects at older ages. PMID- 22670230 TI - Comparative Genetic Mapping and Discovery of Linkage Disequilibrium Across Linkage Groups in White Clover (Trifolium repens L.). AB - White clover (Trifolium repens L.) is an allotetraploid species (2n = 4X = 32) that is widely distributed in temperate regions and cultivated as a forage legume. In this study, we developed expressed sequence tag (EST)-derived simple sequence repeat (SSR) markers, constructed linkage maps, and performed comparative mapping with other legume species. A total of 7982 ESTs that could be assembled into 5400 contigs and 2582 singletons were generated. Using the EST sequences that were obtained, 1973 primer pairs to amplify EST-derived SSR markers were designed and used for linkage analysis of 188 F(1) progenies, which were generated by a cross between two Japanese plants, '273-7' and 'T17-349,' with previously published SSR markers. An integrated linkage map was constructed by combining parental-specific maps, which consisted of 1743 SSR loci on 16 homeologous linkage groups with a total length of 2511 cM. The primer sequences of the developed EST-SSR markers and their map positions are available on http://clovergarden.jp/. Linkage disequilibrium (LD) was observed on 9 of 16 linkage groups of a parental-specific map. The genome structures were compared among white clover, red clover (T. pratense L.), Medicago truncatula, and Lotus japonicus. Macrosynteny was observed across the four legume species. Surprisingly, the comparative genome structure between white clover and M. truncatula had a higher degree of conservation than that of the two clover species. PMID- 22670232 TI - Meeting new challenges with antiplatelet therapy in primary care. PMID- 22670233 TI - The not-so-good old days. PMID- 22670231 TI - The yeast ubr1 ubiquitin ligase participates in a prominent pathway that targets cytosolic thermosensitive mutants for degradation. AB - Mutations causing protein misfolding and proteolysis are associated with many genetic diseases. The degradation of these aberrant proteins typically is mediated by protein-quality control pathways that recognize misfolded domains. Several E3 ubiquitin ligases have been shown to target cytosolic misfolded proteins to the proteasome. In this study, we characterized a panel of more than 20 cytosolic thermosensitive mutants from six essential genes in Saccharomyces cerevisiae. These wild-type proteins are stable at restrictive temperature. In contrast, we found that a large portion of the mutants is degraded at nonpermissive temperature in a proteasome-dependent manner. Approximately one third of the assessed unstable mutants are targeted by the Ubr1 ubiquitin ligase. In two cases, efficient degradation of the thermosensitive mutants is abrogated in the absence of Ubr1 alone, whereas in a third case it is reliant on the dual deletion of Ubr1 and the nuclear E3 ligase San1. We found that the impairment of the degradation of these quality control substrates at the restrictive temperature is associated with the suppression of thermosensitive phenotype. This study confirms that Ubr1 plays an important role in the degradation of cytosolic misfolded proteins and indicates that degradation mediated by protein quality control is a major cause for the conditional lethality of mutated essential genes. PMID- 22670234 TI - Sports concussion: a return-to-play guide. PMID- 22670235 TI - Acute respiratory tract infection: a practice examines its antibiotic prescribing habits. AB - PURPOSE: We wanted to better understand our practice behaviors by measuring antibiotic prescribing patterns for acute respiratory tract infections (ARTIs), which would perhaps help us delineate goals for quality improvement interventions. We determined (1) the distribution of ARTI final diagnoses in our practice, (2) the frequency and types of antibiotics prescribed, and (3) the factors associated with antibiotic prescribing for patients with ARTI. METHODS: We looked at office visits for adults with ARTI symptoms that occurred between December 14, 2009, and March 4, 2010. We compiled a convenience sample of 438 patient visits, collecting historical information, physical examination findings, diagnostic impressions, and treatment decisions. RESULTS: Among the 438 patients, cough was the most common presenting complaint (58%). Acute sinusitis was the most frequently assigned final diagnosis (32%), followed by viral upper respiratory tract infection (29%), and acute bronchitis (24%). Sixty-nine percent of all ARTI patients (304/438) received antibiotic prescriptions, with macrolides being most commonly prescribed (167/304 [55%]). Prescribing antibiotics was associated with a complaint of sinus pain or shortness of breath, duration of illness >=8 days, and specific abnormal physical exam findings. Prescribing rates did not vary based on patient age or presence of risk factors associated with complication. Variations in prescribing rates were noted between individual providers and groups of providers. CONCLUSIONS: We found that we prescribed antibiotics at high rates. Diagnoses of acute sinusitis and bronchitis may have been overused as false justification for antibiotic therapy. We used broad spectrum antibiotics frequently. We have identified several gaps between current and desired performance to address in practice-based quality improvement interventions. PMID- 22670236 TI - Sudden visual loss and weakness in a young woman with migraines. PMID- 22670237 TI - Reducing the risk of breast cancer: A personalized approach. PMID- 22670238 TI - Treating pulmonary embolism at home? PMID- 22670239 TI - Clinical inquiries. Can probiotics safely prevent recurrent vaginitis? PMID- 22670240 TI - Obstipation unresponsive to usual therapeutic maneuvers. PMID- 22670241 TI - An anticoagulation option for nonvalvular atrial fibrillation. PMID- 22670242 TI - The treatment of gout. PMID- 22670243 TI - Managing type 2 diabetes in men. AB - The growing epidemic of T2DM requires intervention to assist patients who have been diagnosed to better manage the disease, to reduce the risk of developing the disease in those who have not yet been diagnosed, and to manage the associated complications. In addition to individualizing interventions based on a patient's needs, concerns, and capabilities, taking gender into account is necessary. In otherwise healthy people, several independent factors appear to pose a higher risk of T2DM in men relative to women, including systolic hypertension, regular smoking, and alcohol intake >= 40 g/d. At the same time, men achieve greater risk reduction from moderate daily alcohol intake and a diet high in fish and seafood, low-fat dairy products, whole grains, and magnesium. Once diagnosed with T2DM, men generally fare better than women regarding the risk for CVD; they also have a better prognosis after MI and a lower risk of death overall from CVD. Possible independent risk factors for CVD in men with T2DM that are especially important may include hypertension, poor glycemic control, and low HDL-C levels. Psychosocial complications, such as depression, are less likely in men with T2DM. However, men expend less effort coping, are less likely to utilize healthcare services, and are less informed about treatment options. Although men have a lower expectation of the benefit of self-management, they find support from family and friends more helpful than do women, but they are fearful of losing control of their disease. Taking these gender differences into account should prove helpful as family care physicians work with men to reduce their risk of developing T2DM and in helping men diagnosed with T2DM to better self-manage their disease. PMID- 22670244 TI - Coronary heart disease in men. AB - Elimination of key risk factors such as dyslipidemia and hypertension is important for reducing cardiovascular events later in life. A medical history, physical examination, and laboratory determination of lipid and glycosylated hemoglobin levels provide a good assessment of cardiovascular risk. A statin is first-line therapy for reducing LDL-C, which is the primary lipid target in most patients. High-dose statin therapy may be required to reach desired target levels. The choice of initial antihypertensive therapy is based on patient comorbidities and drug side effects; however, most patients require combination antihypertensive therapy to reach goal. The combination of this multifactorial risk approach along with smoking cessation and modification of other risk factors should complement current and future cardiovascular care for men. PMID- 22670245 TI - Addressing key questions with statin therapy. PMID- 22670246 TI - A treatment plan is presented at each management step. Introduction. PMID- 22670247 TI - Managing the multiple symptoms of benign prostatic hyperplasia. PMID- 22670248 TI - Dentistry: A global profession. PMID- 22670249 TI - Predictability of surgical techniques used for coverage of multiple adjacent gingival recessions--A systematic review. AB - OBJECTIVE: Predictable coverage of multiple adjacent gingival recessions (MAGRs) is a major challenge for clinicians. Although several surgical techniques have been proposed to treat MAGR, it is still unclear as to what extent the proposed approaches may lead to predictable root coverage. The aim of this article is to identify the predictability of the available surgical techniques used to achieve complete root coverage (CRC) of Miller Class I, II, and III MAGRs. METHOD AND MATERIALS: A search of the PubMed database was performed. Additional hand searching and a search for gray literature were also conducted. Due to the heterogeneity of the data, no meta-analysis could be performed. RESULTS: The search resulted in the selection of 16 publications analyzed in this review. In Miller Class I and II MAGRs, the coronalIy advanced flap (CAF) and the modified coronally advanced flap (MCAF) yielded a CRC ranging from 74.6% to 89.3% and a mean root coverage (MRC) ranging from 91.5% to 97.27% at 6 to 12 months following surgery. In Miller Class I and II recessions, the results obtained with MCAF were maintained for up to 5 years (CRC ranging from 35% to 85.1%), as indicated by two studies. One study has indicated that MCAF + connective tissue grafting (CTG) may improve the long-term stability of CRC compared with MCAF (35% CRC without CTG vs 52% CRC with CTG). In Miller Class I and II MAGRs, the use of CTG in conjunction with CAF, MCAF, coronally positioned pedicle (CPP), double pedicle graft (DPG), or the supraperiosteal tunnel technique yielded higher CRC or MRC than with bioabsorbable membranes, acellular dermal matrix (ADM), or platelet-rich fibrin (PRF). In Miller Class III MAGRs, the modified coronally advanced tunnel (MCAT) and CTG with and without an enamel matrix derivative resulted in 38% CRC and in 82% to 83% MRC, respectively. CONCLUSION: The present findings indicate that in Miller Class I and II MAGRs, CAF or MCAF with or without CTG may lead to predictable CRC; the CRC obtained with MCAF were maintained over a period of 5 years; the use of CTG appears to improve the long-term stability of the MCAF; and the use of CTG in conjunction with CAF, MCAF, CPP, DPG, or the supraperiosteal tunnel technique appear to yield higher CRC or MRC than the use of bioabsorbable membranes, ADM, or PRF. Also, MCAT plus CTG appears to represent a valuable technique for the treatment of Miller Class III MAGRs. PMID- 22670250 TI - Effect of intraoral scanning on the passivity of fit of implant-supported fixed dental prostheses. AB - OBJECTIVES: Passive fit between restorations and implants is considered a significant factor in preventing mechanical and biologic failures in implant dentistry. Since impression taking and master cast fabrication have been shown to cause substantial errors, it was the aim of this study to evaluate the effect of intraoral scanning on the passivity of fit of three-unit cement-retained implant supported fixed dental prostheses (FDPs). METHOD AND MATERIALS: Conventional and optical impressions (n = 10) of an in vitro situation with two implants in the mandibular left quadrant were made. Based on the scans, 10 FDP frameworks were CAD/CAM fabricated from zirconia ceramic; stereolithographic casts were also made. On both the stereolithographic casts and the casts obtained from the conventional impressions, 10 frameworks were waxed and cast in dental training alloy. Subsequently, all samples were cemented on the in vitro model, while the strains emerging were recorded for statistical analysis (MANOVA with Pillai trace; beta = .05). RESULTS: The restorations fabricated on the stereolithographic casts showed significantly lower levels of strain than the conventionally fabricated ones (P = .013). No significant difference could be found between conventionally and CAD/CAM-fabricated frameworks (P = .080). CONCLUSION: Intraoral digitization of dental implants appears to be at least as precise as conventional impression taking and master cast fabrication using prefabricated transfer components and laboratory analogs. PMID- 22670251 TI - Metastases and primary tumors around dental implants: A literature review and case report of peri-implant pulmonary metastasis. AB - OBJECTIVE: To perform a literature review on peri-implant metastases and primary malignoma and report a case of a pulmonary metastasis around dental implants of the anterior mandibular jaw that mimicked peri-implantitis. METHOD AND MATERIALS: A literature search of publications from June 1980 to June 2011 in the PubMed/Medline database was performed to collect information about the type, incidence, and localization of malignant primary tumors and metastases around dental implants and to evaluate potential risk factors. A descriptive statistic was performed based on the collected data with regard to the type and/or origin of tumor, its localization, and the patient's age and sex. RESULTS: A total of 1,795 articles were considered for evaluation. Peri-implant metastases are described in three articles, and peri-implant primary tumors were found in 14 publications. Of all peri-implant metastases, no associated risk factors are mentioned. Those of the peri-implant tumors are alterations of the peri-implant mucosa (such as oral lichen planus, verrucous leukoplakia, and ulcer). Most of the primary tumors are squamous cell carcinoma. The mean age of the patients with peri-implant metastases was 68 years; for the peri-implant primary tumors, it was 71 years. CONCLUSION: Peri-implant metastases and primary tumors are rare. Every untypical or refractory reaction to the treatment of peri-implantitis is suspicious for malignancy as long as the contrary remains unproven. PMID- 22670252 TI - Long-term clinical evaluation of platelet-rich plasma in the treatment of human periodontal intraosseous defects: A comparative clinical trial. AB - OBJECTIVE: To compare the long-term clinical outcomes obtained by the combination of platelet-rich plasma (PRP) and a porous hydroxyapatite at the test site with those obtained from the use of a mixture of hydroxyapatite and saline at the control site in the treatment of human intraosseous defects. METHOD AND MATERIALS: Sixty healthy, nonsmoking subjects diagnosed with chronic periodontitis were included in this study. Using a split-mouth design, intraosseous defects were surgically treated with a combination of PRP and a porous hydroxyapatite or a mixture of hydroxyapatite and saline. Clinical measurements and radiographic evaluation were performed at baseline and 1 and 4 years postoperatively. RESULTS: When compared with baseline, the 1-year results showed no significant changes. However, the 4-year results indicated that while both treatment modalities resulted in significant changes in all clinical parameters (probing depth, relative attachment level, gingival recession, and intraosseous defect fill; P < .001), the test group exhibited statistically significant changes compared with the control group: probing depth reduction, 5.8 +/- 0.49 mm vs 4.0 +/- 0.45 mm (P < .0001); clinical attachment gain, 5.4 +/- 1.2 mm vs 3.1 +/- 1.1 mm (P < .0001); and defect fill, 3.2 +/- 0.8 mm vs 2.1 +/- 0.6 mm (P < .0001). CONCLUSION: Treatment with a combination of PRP and hydroxyapatite compared with hydroxyapatite with saline led to a significantly more favorable clinical improvement in intraosseous periodontal defects. PMID- 22670253 TI - Rapid progression of an idiopathic leukoplakia to a proliferative verrucous leukoplakia lesion and then squamous cell carcinoma. AB - The article reports a case of oral proliferative verrucous leukoplakia (OPVL) in a 76-year-old woman, underscoring how an otherwise inconspicuous white plaque lesion can rapidly turn into a phase of verrucous carcinoma and subsequently squamous cell carcinoma. PMID- 22670254 TI - The relationship of periodontal disease severity to serum and GCF substance P levels in diabetics. AB - OBJECTIVE: To compare circulating and gingival crevicular fluid (GCF) substance P concentrations in well- and poorly controlled type 2 diabetic patients with chronic periodontitis. METHOD AND MATERIALS: Forty-five serum and 90 GCF samples were collected from diabetic patients with periodontal disease, and the concentrations of substance P were quantified by radioimmunoassay. RESULTS: Serum substance P levels were higher in the poorly controlled diabetic group than in patients with good glycemic control (P = .01); within the poorly controlled group, patients with severe attachment levels had the highest circulating substance P levels (P = .02). Additionally, the diseased sites showed higher substance P levels than control sites (P = .0016). The GCF substance P concentrations in diseased sites correlated significantly with clinical findings such as Plaque Index (r = 0.51, P = .001) and bleeding on probing (r = 0.35, P = .029). CONCLUSION: Within the limits of this study, our preliminary findings indicate that periodontal inflammation may influence circulating and GCF substance P levels in poorly controlled diabetic subjects. PMID- 22670255 TI - Use of the connective tissue graft for the coverage of composite resin-restored root surfaces in maxillary central incisors. AB - The purpose of this article is to report the use of the subepithelial connective tissue graft technique combined with the coronally positioned flap on a composite resin-restored root surface to treat Miller Class I gingival recessions associated with deep cervical abrasions in maxillary central incisors. Clinical measurements, including gingival recession height, probing depth, and bleeding on probing (BoP), were recorded during the preoperative clinical examination and at 2, 6, 12, and 24 months postoperatively. During the follow-up periods, no periodontal pockets or BoP were observed. The periodontal tissue of the teeth presented normal color, texture, and contouring. In addition, it was observed that creeping attachment had occurred on the restoration. This case report shows that this form of treatment can be highly effective and predictable in resolving gingival recession associated with a deep cervical abrasion. PMID- 22670256 TI - Antibacterial activity and adhesive properties of a chitosan-containing dental adhesive. AB - OBJECTIVE: To evaluate the antibacterial activity of adhesive resin incorporating chitosan as well as the adhesive characteristics. METHOD AND MATERIALS: An experimental adhesive was prepared by adding 0.12%, 0.25%, 0.5%, and 1% (w/w) chitosan solution to Single Bond adhesive resin. The solution of chitosan was prepared by dissolving 2 g of chitosan powder in 1 liter of 1% (v/v) acetic acid. Single Bond without chitosan was used as a control. The antibacterial activity was evaluated using a direct contact test against Streptococcus mutans. The viscosity, degree of conversion, pH, and microtensile bond strength (MUTBS) values of the experimental adhesives to dentin were evaluated. Data were analyzed using the ANOVA and Tukey tests. Statistical significance was set at the .05 probability level. RESULTS: The antibacterial properties of freshly prepared and aged experimental adhesives incorporating chitosan were found to exhibit an inhibitory effect on the growth of Streptococcus mutans compared with the unmodified adhesive resin (P < .05). The viscosity of the experimental adhesives increased with increasing the concentrations of chitosan incorporation into the adhesive. However, the degree of conversion and pH values decreased with increasing the concentrations of chitosan incorporation into the adhesive. Experimental adhesives incorporating 0.12% and 0.25% (w/w) chitosan showed no significant differences in the MUTBS values compared with the control (P > .05). However, the incorporation of 0.5% and 1% (w/w) chitosan into the dental adhesive significantly decreased the MUTBS (P < .05). CONCLUSION: Adhesive resin that contains 0.12% (w/w) chitosan is a promising antibacterial adhesive that does not adversely affect adhesive properties. PMID- 22670257 TI - Fiber post adhesion to radicular dentin: The use of acid etching prior to a one step self-etching adhesive. AB - The aim of this study was to evaluate the bond strength of fiber posts luted with a one-step self-etching adhesive with the push-out test after phosphoric acid conditioning of the root dentin. Thirty-six single-rooted teeth were endodontically treated. Teeth were sectioned perpendicularly to the cementoenamel junction, and a 10-mm post space was prepared with a calibrated bur. Specimens were then divided into three groups according to the adhesive protocol: A, total etch three steps; B, self-etch one step; and C, 32% phosphoric acid conditioning and self-etch one step. Fiber posts were luted with self-curing resin-based cement. Teeth were cut in 1-mm slices and pushed until failure with an Instron machine. Results were statistically analyzed with the ANOVA and Bonferroni tests (P < .05). Two additional specimens from each group were examined under the scanning electron microscope (SEM). The 32% phosphoric acid significantly influenced the push-out bond strength of fiber posts luted with self-etch adhesives (P < .05). SEM analysis showed a continuous hybrid layer with resin tags and lateral branches in groups A and C, while group B showed smear layer dissolution with poor infiltration of the tubules. PMID- 22670258 TI - Comparative antiplaque and antigingivitis efficacy of a multipurpose essential oil-containing mouthrinse and a cetylpyridinium chloride-containing mouthrinse: A 6-month randomized clinical trial. AB - OBJECTIVE: This 6-month, examiner-blind, single-center, randomized, parallel group clinical trial compared the antiplaque and antigingivitis effects of an essential oil-containing mouthrinse with zinc chloride and sodium fluoride (EO) to a 0.05% cetylpyridinium chloride-containing mouthrinse (CPC) also with fluoride. METHOD AND MATERIALS: Four hundred and eight gingivitis subjects were monitored for the primary outcomes of modified Gingival Index (MGI) and Plaque Index (PI) at baseline and 3 and 6 months. Subjects were randomly assigned to 6 month twice a day unsupervised use of EO, CPC, or negative control rinse in conjunction with normal brushing and flossing. RESULTS: EO was always better than CPC at 3 and 6 months considering all parameters. All benefits allowed by EO increased from 3 to 6 months. CPC was better than the negative control at 3 and 6 months with respect to whole mouth plaque, and the proportion of more severe sites (baseline scores >= 3) in PI and MGI. At 6 months, CPC did not differ from negative control in relation to whole mouth MGI reduction, proximal MGI reduction, and percentages of sites improved over baseline in PI and MGI. CONCLUSION: This new EO mouthrinse provided superior clinical benefits to CPC and demonstrated increasing plaque and gingivitis reductions over 6 months. Our findings support the regular long-term use of the EO mouthrinse and selection over a 0.05% CPC rinse for better efficacy. PMID- 22670259 TI - The effect of strontium and combinations of strontium and fluoride on the remineralization of artificial caries lesions in vitro. AB - OBJECTIVE: To determine the effect of relatively low strontium concentrations on enamel remineralization and investigate the dose-response effects of strontium and fluoride combinations on the remineralization of artificial caries lesions in vitro. METHOD AND MATERIALS: Artificial caries lesions were created in 135 bovine enamel specimens. Lesion severity was analyzed using transverse microradiography (TMR) and quantitative light-induced fluorescence (QLF). The specimens were randomly assigned to nine treatment groups based on lesion volume after lesion creation, as measured by TMR. Treatment groups were based on a 3 x 3 factorial design (0/0.05/0.1 ppm fluoride and 0/10/15 ppm strontium). Lesions were remineralized at 37 degrees C for 14 days in artificial saliva, which was supplemented or not with NaF and/or SrCl2 x 6H2O. Lesion remineralization was assessed using QLF and TMR. Data were analyzed using ANOVA. RESULTS: For the TMR data, lesion remineralization in the 10 ppm strontium + 0.05 ppm fluoride group was significantly higher than in all other groups (P < .05) except the 0 ppm strontium + 0.05 ppm fluoride group (P = .06). The 10 ppm strontium + 0 ppm fluoride group exhibited significantly less remineralization than the 0 ppm strontium + 0 ppm fluoride group (P = .048). For the QLF data, intergroup differences were not the same as for the TMR analysis. The QLF measurement was only moderately correlated with TMR mineral loss (r = -0.37). CONCLUSION: Strontium alone did not improve the remineralization of artificial caries lesions under the chosen in vitro conditions. However, a synergistic effect between the combination of fluoride and strontium was found at specific concentrations. PMID- 22670260 TI - Proceedings of the XIIIth International Symposium on Advances in Targeted Therapies, April 6-9, 2012, Dubrovnik, Croatia. PMID- 22670261 TI - Special issue dedicated to Paul Letourneau. PMID- 22670262 TI - Biotechnology investment: Gains and losses. PMID- 22670263 TI - Turning point: Mayim Bialik. Interviewed by Gene Russo. PMID- 22670264 TI - 12th International Conference on Biomedical Applications of Electrical Impedance Tomography (University of Bath, UK, 4-6 May 2011). PMID- 22670265 TI - A phosphoramidate-based prostate-specific membrane antigen-targeted SPECT agent. AB - BACKGROUND: Prostate-specific membrane antigen (PSMA) remains an active target for imaging and therapeutic applications for prostate cancer. METHODS: In the present study, an irreversible phosphoramidate inhibitor, CTT-54 (IC50 = 14 nM), has been modified to deliver 99mTc-(CO)3-DTPA as a SPECT imaging payload to PSMA+ cells in vivo and in vitro. Percent uptake, competitive binding, and internalization will evaluate the imaging agent in vitro. Preliminary biodistribution and imaging will be utilized for in vivo evaluation. RESULTS: In vitro studies demonstrate that the radiotracer 99mTc-(CO)3-DTPA-CTT-54 exhibits increasing cellular uptake in the PSMA+ LNCaP cells over time. More importantly, it was found that 99mTc-(CO)3-DTPA-CTT-54 is rapidly internalized into LNCaP cells, presumably through the PSMA enzyme-inhibitor complex. In a pilot biodistribution study, increasing accumulation of the radiotracer in LNCaP xenografts was observed from 2 to 4 hr and significant clearance from non-target tissues. CONCLUSIONS: While DTPA may not represent the ideal chelate structure for 99mTc(CO)3, the data provides proof-of-concept support for the development of a next-generation phosphoramidate-based PSMA inhibitor-conjugates for use as SPECT imaging agents. PMID- 22670266 TI - Proceedings of the 6th International Symposium on Alcoholic Liver and Pancreatic Diseases and Cirrhosis, October 20-21, 2011, Fukuoka, Japan. PMID- 22670267 TI - [Proceedings and abstracts of the VIIth International Congress Therapeutic Apheresis, May 28-29, 2010, Alghero, Sardinia]. PMID- 22670268 TI - Pediatric neurological disorder and present nuclear detonation: a hot issue. AB - It is no doubt for the health effect of the radiation from the nuclear detonation from the destroyed nuclear power plant. Due to the present crisis in Japan, the public health concern on this issue should be raised. In pediatric neurology, there are some interesting reports on pediatric neurological disorder and its relationship to leaked radiation. In this specific brief article, the author hereby discusses on the nuclear detonation and pediatric neurological disorder. Although there are some reports on the increased incidence of some pediatric neurological malignancies and congenital neurological anomalies there is no confirmed evidence. Effect on cognitive function is still controversial. The induction of abnormal electroencephalography is also mentioned. The observation on the effect of present crisis in pediatric neurology can provide more information and help better understand this topic. PMID- 22670269 TI - The politics of fraud. Latest takedown meant to spotlight Obama efforts. PMID- 22670270 TI - Dual costs. Feds, states focus on ways to improve care and rein in spending for high-cost patients eligible for both Medicaid and Medicare. PMID- 22670271 TI - Medicaid expenditures by state. Ranked by fiscal 2010 expenditures ($ in millions). PMID- 22670272 TI - Weighing the options. Results unclear in plans for doc payment system. PMID- 22670273 TI - Innovation won't wait. Despite law's uncertainty, CMS awards grants. PMID- 22670274 TI - By the number. Largest U.S. travel nurse staffing firms. Ranked by estimated 2010 U.S. temporary staffing revenue ($ millions). PMID- 22670275 TI - By the number. Largest U.S. per diem nurse staffing firms. Ranked by estimated 2010 U.S. temporary staffing revenue ($ millions). PMID- 22670276 TI - By the number. Largest U.S. locum tenens staffing firms. Ranked by estimated 2010 U.S. temporary staffing revenue ($ millions). PMID- 22670277 TI - In knots over flexibility. Providers hoped for CMS standards on exchanges. PMID- 22670278 TI - Gray economic outlook. Medicare, Medicaid may double? Provider cuts likely. PMID- 22670279 TI - By the numbers. Largest master's programs in health administration. Ranked by total full-time student enrollment in 2011-12 academic year. PMID- 22670280 TI - Fragile forecast. Trustees: control costs to retain quality, availability. PMID- 22670281 TI - By the numbers. Largest patient-satisfaction measurement firms. Ranked by total number of engagements in 2011. PMID- 22670282 TI - Sugar and your heart: sour news about sweets. PMID- 22670283 TI - Light smoking: dangerous in any dose. PMID- 22670284 TI - Distracted driving: fast lane to disaster. PMID- 22670285 TI - On call. As a retired physician, I particularly appreciate "Harvard Men's Health Watch" since it's an easy way for me to learn about new developments in medicine. As a 78-year-old man with an enlarged prostate, I'm particularly interested in your fine articles about BPH. But if memory serves me right, we called the condition "benign prostatic hypertrophy" when I was in practice, but now you call it "benign prostatic hyperplasia." What's the difference? PMID- 22670286 TI - The challenges of evaluation in the Brazilian Unified Health System (SUS). PMID- 22670287 TI - Hospital activities in organ donation program in Saudi Arabia. PMID- 22670288 TI - Authority figures. PMID- 22670289 TI - Research is care. PMID- 22670290 TI - An unintened misrepresentation. PMID- 22670291 TI - Toward universal standards. PMID- 22670292 TI - Uncomfortable humor. PMID- 22670293 TI - Case study. Exploring the limits of autonomy. Commentary. PMID- 22670294 TI - Case study. Exploring the limits of autonomy. Commentary. PMID- 22670295 TI - Case study. Exploring the limits of autonomy. Commentary. PMID- 22670296 TI - Struggle between survival and death: the life experience of Taiwanese older adults with suicidal ideation. AB - The purpose of this study was to use grounded theory to explore the subjective experiences of suicidal ideation among Taiwanese older adults in the community. Fifteen participants ages 66 to 88 were interviewed, and data were analyzed using a constant comparative analysis method. The Struggle Between Survival and Death was defined as the core category. Loss of loved ones, possession, and health was defined as the antecedent condition. The older adults struggled between survival and death during a suicidal ideation process categorized as negative emotions without an outlet, reminiscence about past achievements,lingering or persistent suicidal ideation, and hesitation to commit suicide. Lastly, the participants reported experiencing a meaningless existence in their daily lives. It is crucial to provide sensitive support to older adults who have had loss of life experiences, including providing an outlet to express negative emotions, religious support, reminiscence therapy, or a life review. PMID- 22670297 TI - [Report of the training camp for the scientists to write and review paper]. PMID- 22670299 TI - [Chronic infection and diseases of internal medicine. Introduction]. PMID- 22670298 TI - [Definition and characteristics of the practice guidelines for nosocomial pneumonias in Japan]. PMID- 22670300 TI - [Studies on Lewy bodies on their 100th year: a discussion]. PMID- 22670301 TI - Who--or what--is reading your resume? PMID- 22670302 TI - History always lends perspective. PMID- 22670303 TI - Uncomplicating insulin therapy: strategies for initiation in patients with type 2 diabetes. PMID- 22670304 TI - Contraception counseling: how two simple questions can make a difference. PMID- 22670305 TI - Oral anticoagulants for atrial fibrillation: Which one to choose? PMID- 22670306 TI - The data deluge: the information explosion in medicine and science. PMID- 22670307 TI - Success, professionalism, and the medical student. PMID- 22670308 TI - Through a glass darkly. PMID- 22670309 TI - Paulinia. PMID- 22670310 TI - Allvar Gullstrand, Albert Einstein, and a Nobel dilemma revisited. PMID- 22670311 TI - The anatomy of melancholy: Burton and Osler. PMID- 22670312 TI - The case for integrating public health and medical education and how to do it. PMID- 22670313 TI - Comparison of open and laparoscopic pyeloplasty in ureteropelvic junction obstruction surgery: report of 49 cases. AB - OBJECTIVE: This study aimed to evaluate laparoscopic dismembered pyeloplasty compared with open surgery and to determine whether the morbidity and outcome rates are different in each of these techniques. We report our 10-year experience with open and laparoscopic pyeloplasty at one istitution. METHODS: From February 1999 to October 2010, 49 patients with ureteropelvic junction obstruction were assigned into two groups. 25 patients underwent open surgical pyeloplasty (period 1999-2010) and 24 underwent laparoscopic pyeloplasty (period 2004-2010). 25 patients undergoing open pyeloplasty had a retroperitoneal flank approach. Of the 24 laparoscopic cases 18 had a transperitoneal retrocolic access, 1 had a transperitoneal transmesocolic access and 5 had a retroperitoneal access. In all 49 cases an Anderson-Hynes dismembered pyeloplasty was used. We retrospectively compared the operative time, hospital stay, perioperative complications and follow-up of the two groups. Clinical symptoms were assessed before and after surgery, subjectively. RESULTS: Patients dermographic data were similar between the two groups with mean age of 42 years (range 6-78) and with a male/female ratio of 1:1.45. A crossing vessel could be identified in 37.5% (9/24) with laparoscopy vs. 32% (8/25) in open surgery. Compared with open procedures, laparoscopic procedures were associated with a longer mean operating time (274 vs 143 min), a shorter mean hospital stay (9.9 vs 15.8 day) and the perioperative complication rates were 16.7% for laparoscopic pyeloplasties and 20% for open pyeloplasties. The success rates were 90.5% for laparoscopy and 90.9% for open surgery. Average follow-up was 40.9 month for the laparoscopic group and 72.3 month for the open group. Failed procedures showed no improvement in loin pain or obstruction. CONCLUSIONS: The efficacy (in term of success rate and perioperative complications) of laparoscopic pyeloplasty is comparable to that of open pyeloplasty, with shorter mean hospital stay and better cosmetic results. These findings may suggest, that the laparoscopic dismembered pyeloplasty has the potential to replace open surgery and may be considered the first option for the treatment of ureteropelvic junction obstruction in expert hands. PMID- 22670314 TI - Transperitoneal versus retroperitoneal laparoscopic partial nephrectomy: initial experience. AB - OBJECTIVE: We present the transperitoneal and retroperitoneal approaches to laparoscopic partial nephrectomy and compare the outcomes of each technique. METHODS: Between December 2006 and March 2010, retroperitoneal laparoscopic partial nephrectomy (RLPN) was performed in 23 patients and transperitoneal laparoscopic partial nephrectomy (TLPN) in 26 patients. They were compared regarding surgical technique, operative parameters, postoperative recovery and follow-up data. The 2 approaches used similar operative techniques to control parenchymal bleeding. RESULTS: The patient demographics were similar in both groups. The mean tumour size was 3.1 cm in the retroperitoneal group and 3.4 cm in the transperitoneal group. The difference was not statistically significant (p: 0.095). The mean operative time was significantly longer in the transperitoneal group (215 vs 185 minutes, p: 0.031). The mean warm ischemia time difference was not statistically significant (25 vs 28 minutes, p: 0.102). The mean estimated blood loss (EBL) was greater in the transperitoneal group (254 vs 204 cc, p: 0.003). Moreover, the mean hospital stay was 4.1 days in the RLPN and 4.3 days in the TLPN group (p: 0.303) The difference was not statistically significant. The median follow-up was 11 months (range: 2 to 35) in the retroperitoneal group and 13 months (range 1 to 36) in the transperitoneal group. CONCLUSIONS: Our experience has shown that laparoscopic partial nephrectomy is a safe, feasible technique for patients with small exophytic renal tumours. We believe that the decision regarding the approach should be based on the tumor location on the kidney surface. PMID- 22670315 TI - Comparison of p38MAPK (mitogene activated protein kinase), p65 NFkappaB (nuclear factor kappa b) and EMMPRIN (extracellular matrix metalloproteinase inducer) expressions with tumor grade and stage of superficial and invasive bladder tumors. AB - To identify the molecular mechanisms of bladder cancer invasion pathophysiology. To assess EMMPRIN, p65NFkappaB and p38MAPK expressions which play a role in signal transmission system of muscle and non muscle invasive bladder tumors. Fifty-seven patients with non muscle invasive tumors (mean age 65.2 +/- 16.1) and 34 patients with muscle invasive tumors (mean age 62.2 +/- 20.7) were included in this study. Normal tissue from the same patients' bladders were used as control group. Patients had either TUR or radical cystectomy and paraffin sections were prepared for immunohistochemistry. Expression density was evaluated semiquantitively according to tumor grade and invasion depth. Results were compared with Mann Whitney U, Wilcoxon W, Chi Square and variation analysis tests. MAPK and EMMPRIN expression was increased according to tumor grade (p < 0.05). These expressions were also significantly higher in muscle invasive tumors than in non muscle invasive ones (p < 0.05). In normal tissue samples of both TUR and radical cystectomy materials, EMMPRIN, NFkappaB and MAPK expressions were lower than in tumor samples (p < 0.05). NFkappaB wasn't related to tumor grade/stage (p > 0.05). It can be stated that MAPK and EMMPRIN expression is related to the grade of bladder tumor and that NFkappaB positivity is not related to the grade/stage of the disease. In future positivity of lymph nodes and visceral metastasis and survival must be assessed to define the relationship with the expressions in long term follow up studies involving a larger number of patients. PMID- 22670316 TI - Analysis of survival in radical and postoperative radiotherapy for prostate cancer. AB - PURPOSE: To analyze survival and complications in high dose 3D conformal radiotherapy (3DCRT) patients treated with curative and post-operative intent and compare radical surgery + radiotherapy (RT) patients vs. RT only patients. MATERIAL AND METHOD: 103 patients were treated curatively (RAD), 94 postoperatively (POST-OP). The mean age was higher in RAD group (72.6 years, range 56.4-85.1) than in POST-OP group (65.4 years, 43.9-77) (p < 0.0001). According to NCCN prognostic classification 13 (12%) patients was low risk, 48 (47%) intermediate risk and 42 (41%) high risk in RAD group. In POST-OP group 13 (14%) patients were low risk, 37 (40%) intermediate risk and 44 (46%) high risk. Hormone Therapy (HT) was administered in 98 patients (95%) in RAD and in 45 patients (47.8%) in POST-OP. Patients were treated with a three-dimensional conformal radiotherapy (3D-CRT). In RAD 15 (15%) were alive with disease (AWD), 5 (5%) dead of disease (DOD) and 10 (10%) dead of other cause (DOC); in POST-OP 14 (14.8%) were AWD, 2 (2%) DOD and 3 (3%) DOC. The prescription dose was 80 Gy in 2 Gy fractions in the RAD group, and 70 Gy in 2-Gy fractions in the POST-OP, respectively. RESULTS: No biochemical or clinical relapse was found in low risk patients in RAD group and 1 relapse in POST-OP group. The largest number of relapses occurred and in intermediate-high risk in RAD (39%) and POST-OP group (33%). In the cause-specific survival analysis no significant differences were found in high risk group between RAD and POST-OP (p = 0.9). In the biochemical relapse-free survival (bRFS) at 5 years analysis no significant differences were found in the high risk group between RAD and POST-OP (p = 0.1020). CONCLUSION: RT in RAD low- risk is very effectiva. RAD and POST-OP RT were well tolerated with a very low toxicity. The cause-specific survival at 5 years was 95% and 97% for the two groups of treatment, RAD and POST-OP respectively (Log-rank test p = 0.2908). PMID- 22670317 TI - Regular ultrasound examination of transplanted kidneys allows early diagnosis of renal cell carcinoma and conservative nephron sparing surgery. AB - INTRODUCTION: The development of malignancies is a relevant long-term complication of organ transplantation. Carcinoma of native kidney accounts for up to 5% of all malignancies found in transplant recipients. Primary clear cell type renal cell carcinoma (RCC) usually arises in the native kidneys. Its occurrence in the renal allograft has been reported infrequently. CASE PRESENTATION: We report a rare case of de novo RCC in a kidney allograft in a 41 years-old woman. Routine ultrasonography denoted a poorly marginated hypoechoic mass at the inferior pole of transplanted organ, confirmed by computed tomography which showed a lesion of 32 mm in diameter with characteristic radiological signs of RCC. The patient underwent nephron sparing surgery (NSS). At histological examination the tumor was T1-T2, N0, M0 with negative margins. At five years after NSS no significant impairment of renal function or recurrence was observed. CONCLUSION: Primary carcinomas of the kidney can be detected after transplantation in the native or transplanted kidney. According to the European Guidelines on the long-term management of kidney transplantation, all recipients should have regular ultrasonography of native and allograft kidneys to screen for cancer, which occurs at a much higher incidence in transplanted patients. NSS is a safe and efficient procedure for the treatment of RCC in renal graft, resulting in the preservation of renal function and in long-term cancer control. PMID- 22670318 TI - Solitary giant sarcomatoid carcinoma of the bladder. A case report. AB - A case of sarcomatoid carcinoma of the bladder (SCB) presenting as a giant intravesical mass in a 75-year-old man complaining of lower urinary tract swmptoms (LUTS), abdominal pain and fever is reported. SCB is a rare (0.1% of all primary bladder tumors), aggressive cancer with a complex histology (a biphasic tumor with malignant epithelial and mesenchymal elements) and poor prognosis. PMID- 22670319 TI - Renal cell carcinoma and synchronous thyroid metastasis with neoplastic thrombosis of the internal jugular vein: report of a case. AB - A case of thyroid metastasis of a renal clear cell carcinoma is presented. The fine-needle aspiration cytology pointed out the primary tumor origin. The patient underwent robot-assisted radical nephrectomy and contextual thyroidectomy. During the operative procedure, a neoplastic thrombus extending from the thyroid metastasis and protruding into the internal jugular vein was found. As a result, thrombectomy and ligation of the internal jugular vein were required. In cases of single synchronous thyroid metastases form RCC, radical surgery should be advisable. Robotic approach allows to associate major surgery procedures, as nephrectomy, with radical metastasectomy. PMID- 22670320 TI - Transvestibular urethrolysis. AB - OBJECTIVES: Bladder outlet obstruction with obstructive and irritative urinary symptoms may be a complication of surgery for female urinary incontinence. In presence of persistent symptoms the therapy is surgical and usually consists in an accurate urethrolysis. The way of approach is generally transvaginal. In this paper we propose and describe our experience with a transvestibular approach. METHODS: From 1995 to 2009 18 women who had undergone anti-incontinence surgery (TVT 12 pts, TOT 3 pts, Burch retropubic colposuspension 3 pts) with obstruction and/or irritative symptoms underwent to a transvestibular urethrolysys. Five patients had urinary retention the other patients had post voiding residual urine > 100 ml. With a scalpel blade a circum-meatal incision was performed and the urethra was progressively freed, dissecting just below the os pubis upwards and on the vaginal wall downwards untethering it under direct vision obtaining a complete circular freeing of the urethra; at the end the urethral meatus is repositioned with circular stiches. RESULTS: The operation lasts between 20 and 40 minutes. Urethral catheter was left in place for 24-48 hours and no complications were observed. The post-voiding residual urine decreased in all the cases and the irritative symptoms were reduced. CONCLUSIONS: The transvestibular approach represents a safe and effective approach to urethrolysis undependently of the type of anti-incontinence surgey carried out. Urethrolysis has the advantage of working in a relatively unscarred tissue, can allow a complete untethering of the urethra even in the retropubic space and leaves the vaginal wall intact. PMID- 22670321 TI - Blue nevus of the prostate: incidental finding in radical prostatectomy specimen with a pre-operative echographic image of peripheral hypoechogenic nodule. AB - Blue nevus is a stromal melanin deposition, which is microscopically characterized by deeply pigmented melanin-filled spindle cells within the fibromuscular stroma. Cases with prominent melanosis such as those with grossly visible pigment are uncommon. Melanocytic lesions of the prostate are incidental findings with no evidence of malignant transformation. There have only been very few reports of a malignant melanoma of primary prostatic origin. We report an incidental finding of a blue nevus of the prostate, in a radical prostatectomy specimen, in a 64-years-old man with a pre-operative ecographic image of peripheral hypoechogenic nodule. The are very few reports of blue nevi associated to prostatic adenocarcinoma, but none has been evidentiated before surgery as a distinct ultrasound lesion interpreted as adenocarcinoma, therefore inducing the clinician to perform biopsies and consequently a radical prostatectomy. PMID- 22670322 TI - Urinary incontinence in adults: nurses' beliefs, education and role in continence promotion. A narrative review. AB - INTRODUCTION: Urinary incontinence (UI) has a high prevalence worldwide, in both genders; the available data suggest that the number of incontinent people will dramatically increase in the next few years. The costs generated by UI are similar to those induced by HIV and breast cancer. We aimed to investigate nurses' beliefs, knowledge and educational situation in the field of urinary continence. METHODS: We performed a narrative review of literature, by searching qualitative and qualitative studies (2006-11) in PubMed, CINAHL and the Cochrane Library. Papers investigating pharmacological and/or surgical intervention were excluded. Only studies referred to adults have been taken into consideration. RESULTS: Prevalence ranges from 25 to 45% in women; in men, post-prostatectomy UI occurs in a median of 10-15% of the total cases. Benign prostatic hyperplasia, which affects 50% of men aged 50 to 60, is often associated with urge incontinence. The yearly individual expense for pads in Italy has been estimated to be as high as 913 euros in 2004. People often do not know about the possible solutions to UI; nurses seem to lack education in continence promotion, notwithstanding the proven effectiveness of the conservative interventions they could perform in autonomy. In Italy, few academic programs offer nursing education in this field. CONCLUSIONS: Urinary incontinence seems to be an underestimated problem; nurses often lack proper education in continence promotion. Academic, structured courses would be a solution; however, since education itself is not sufficient to really improve clinical practice, organizational support would be required to effectively promote continence in the broadest possible population. This would be a long-term investment for both quality of care and costs. Further studies are needed, regarding conservative management of UI; research could lead to a strong integration between clinical and academic branches of nursing, resulting in good quality evidence for clinical practice. PMID- 22670323 TI - Open for business: private networks create a marketplace for health information exchange. AB - Large health systems and their IT vendors are creating private information exchange networks at a time when federally funded state operations are gearing up for launch, Is there room for private and public offerings in the new HIE marketplace? PMID- 22670324 TI - Partnering on patient matching: an HIM committee helps steer a RHIO's patient index. PMID- 22670325 TI - Putting the HIM in IM: assimilating integrative medicine into clinical documentation. PMID- 22670326 TI - EHR 2014: highlights of the proposed stage 2 certification rule. PMID- 22670327 TI - Untangling HIE: patchwork regulations, standards complicate health information exchange. PMID- 22670328 TI - Converting data to ICD-10 with GEMs: reference mapping tools will aid in system transition. PMID- 22670329 TI - Trends in E-discovery: Four cases provide a glimpse of healthcare litigation's future. PMID- 22670330 TI - The 10 security domains (updated). PMID- 22670331 TI - Engaging physicians in ICD-10 planning: the documentation link. PMID- 22670332 TI - Coding diabetes mellitus in ICD-10-CM: improved coding for diabetes mellitus complements present medical science. PMID- 22670333 TI - Mandates encourage E-discovery. PMID- 22670334 TI - [Cell phones: health risks and prevention]. AB - The paper describes first of all the electromagnetic radiation of cellular phones and presents the physical parameters used to measure and evaluate the absorption of emissions of radio stations and cellular phones. It then presents selected research results of the experimental studies in vivo and in vitro which examine the biological effects of the emissions of cellular phones. The review of the epidemiologic evidence focuses in particular the epidemiologic studies on the use of cell phones and brain tumours, identifying some of the reasons of the conflicting results obtained. Studies dealing with the health risks involved in the increasing use of cellular phones by adolescents and children, more sensitive to this exposure, are also presented showing the need for special caution. The problem of hypersensitivity observed in some individuals is also briefly discussed. Finally the paper presents a summary of the main prevention measures necessary in order to reduce the risks in the framework of the "precautionary principle" including prevention policies and exposure limits in various countries. PMID- 22670335 TI - [Which prevention programs effectively reduce the risk of alcohol consumption in young people?]. AB - Alcohol consumption among young people is a major public health problem and the Italian National Health Institute considers it the leading cause of death for people under 24 years old, mainly due to road accidents. This study summarizes the evidence emerging from three Cochrane Collaboration reviews, aiming to orient the choice of alcohol prevention programs for young people. The first review considered schemes implemented at school to prevent alcohol consumption under 18 years of age; the second concerned studies on programs to reduce alcohol abuse by means of social norms; the third examined 56 trials on schemes for preventing young people from drinking. In the first review, 6 of 11 alcohol prevention schemes showed some signs of efficacy, and 14 of 39 schemes to combat substance abuse generally induced a significantly alcohol use reduction. The second review included three specific programs for alcohol-related problems with a > 17-month follow-up and they were effective. In the third review, 15 of 39 schemes proved effective in the short-term, 9 of 12 with medium follow-up were no longer effective (and alcohol consumption even increased in 2), while 3 long-term trials and 2 of 3 community schemes proved effective. These Cochrane reviews did not assess all strategies for preventing alcohol abuse in the young which have been implemented in different countries, because many interventions has been conducted spontaneously without any evaluation of their efficacy. An international registry on substance abuse prevention measures is warranted, with shared criteria for assessing their effects, to orient public health policies. PMID- 22670336 TI - [Assessment of the hygienic and sanitary conditions of housing in a sample in Chieti (central Italy)]. AB - The study describes the housing conditions of 106 dwellings in the town of Chieti (Abruzzo region, central Italy), inspected by Local Health Authority, in the period between the 1st of January 2009 and the 28th of February 2011. In 59.4% of them lived Italians, while in the remaining 40.6% lived foreigners. 35.8% of the houses met minimum law requirements, 24.5% were anti-hygienic, 24.5% anti hygienic and overcrowded, 13.2% overcrowded, 1.9% uninhabitable. The main issues were moisture and molds (52.8%). The second one was the inadequacy of floor area in relation with inhabitants (37.7%). Other problems were bedrooms (9.4%), baths (8.5%) and kitchens not complying minimum law requirements, but also not sufficient both ceiling hights (3.7%) and windows (2.8%) of rooms. Considering that human population in richest countries spend up to 90% of their lives in indoor environment, especially at home, the links between housing and health are really strong, and more must be done to improve general consideration of these themes both in general population and involved professionists (i.e. physicians, other health professionists, social workers, architects and engineers). PMID- 22670337 TI - [Prioritizing prescriptions in a ambulatory care setting: a tool to achieve appropriateness of care in public health management]. AB - Waiting lists are one of the main Public Health issues within developed countries. To promote appropriateness about General Practitioners' (GPs) prescriptions, during 2009 the project "Priority setting in outpatient prescriptions" in Latium Region has been approved. Regional referees, Latium Public Health Agency managers and advisors, managers and advisors of three Local Public Health Units (LPHUs) within the Latium region and some voluntarily recruited General Practitioners (each one with more than 800 patients enrolled) were included in a team work with the duty to develop the project. During two selected months of 2010, 46 GPs have forwarded overall 2.229 medical prescriptions. The six most numerous prescriptions were picked out and analyzed by the team work. 42% of these prescriptions were identified as belonging to category D of the priority level--"standard", while 42% and 41% of prescriptions bore the expressions of "control" and "diagnostic purpose" respectively. Among these ones, 75% were represented by bilateral mammography, prescribed to women aged between 50 and 69 years: but for those people bilateral mammography is already provided free of charge within the regional program of breast cancer screening, making the routine prescription by their physician a useless duplication, unacceptable in a healthcare system of good quality. Therefore at the conclusion of the project, the team work suggests proper standards be applied by healthcare professionals and GPs to achieve a significant objective: mammography appropriateness prescriptions. PMID- 22670338 TI - [Concept analysis of the nursing profession, published from 1994 to 2008]. AB - Concept analysis is a research method in which concepts are examined in a logical and systematic fashion to form clear and rigorous conceptual definitions. To describe the concept analyses published between 1994 and 2008 and identify the emerging tendencies in the Nursing discipline, a two-staged study has been developed. In the first stage a systematic review of the literature was conducted: research published in the journals indexed in the MedLine, CINAHL and Cochrane databases were judged eligible, if they reported the theme of 'concept analysis' and 'nursing' in the title or in their key words and were published in English language. In the second stage, the articles that emerged were subjected to a content analysis. Some 158 concept analyses emerged, on average 10/year (range 1-22, median 11, +/- 5.6): these regarded 129 different concepts. Ninety one (57.6%) concepts were focused on the nursing profession, while 67 (42.4%) were focused on the patients. Although in a few cases the effort made by the researchers moved toward the definition of new concepts, in others it appeared oriented toward including in Nursing some typical concepts from other disciplines, thus tracing an expansion of the domain of the Nursing discipline. Monitoring over time the concepts analysed constitutes an important research area to comprehend, both at a national and international level, the progressive evolution of the Nursing discipline. PMID- 22670339 TI - [Epidemiologic situation of viral hepatitis type A in Campania: perspectives of prevention and control of infections at the local level]. AB - In the Region Campania (South Italy) the Hepatitis A infection reveals to be very present, despite of worldwide decreasing trend. Particularly Naples has a high incidence pathology as compared with other regional districts: the propose of this work is analysing the reasons by analysis of small but representative sample of this pathology. Health District of ASL Napoli 1 Center provides us with the notifications of this disease. The cases disease are attributable to consumption of contaminated shellfish purchased from mainly non-authorized dealers present on all city territory. A properly educational, of the population, increased repression control of dealers, careful monitoring of illegal dumping, can reduce the incidence of EVA in city live Naples. PMID- 22670340 TI - [Enterobiasis in pediatric subjects in north-western Italy: a study of home remedies]. AB - The present study examines the most common home remedies in the Piedmont region of northwest Italy currently used in the treatment of pediatric enterobiasis, commonly known as pinworm infection. The remedies in question, typically based on popular beliefs and as such are nearly useless, were noted through interviews with subjects who had come to the local Hygiene and Public Health Services offices for information about pinworm prevention and treatment. Analysis of replies by the subjects clearly indicates that local families are ill-prepared to recognize the symptoms this parasitic infection; often it is confused with pediatric ketosis, therefore leading to inappropriate treatment which at times may be potentially harmful to the patient. PMID- 22670341 TI - [Vibrio spp. infections of clinical significance and implication for public health]. AB - Vibrio spp. infections still are a Public Health concern. Vibrio spp. can be found in marine, estuarine, and freshwater environments, and can be able to cause diseases in fish, shellfish, mammals, as well as in humans. Since '80 to date, the number of species within the genus increased from 21 to more than 100. The most important is Vibrio cholerae, the etiological agent of the cholera, responsible of seven pandemics; serotypes O1 and O139 can produce cholera toxin, while serotypes non-O1/non-O139 are generally associated with sporadic cholera cases and extraintestinal infections. Vibrio parahaemolyticus is an important cause of gastroenteritis associated with contaminated seafood consumption, whereas Vibrio vulnificus and V. alginolyticus can be related to wound infections or seafoodborne primary septicemia in immunocompromised patients. Disease prevention is mainly based on the application of proper individual or collective preventive measures. PMID- 22670342 TI - Tom the European. PMID- 22670343 TI - Giving subjects the eye and showing them the finger: socio-biological cues and saccade generation in the anti-saccade task. AB - Pointing with the eyes or the finger occurs frequently in social interaction to indicate direction of attention and one's intentions. Research with a voluntary saccade task (where saccade direction is instructed by the colour of a fixation point) suggested that gaze cues automatically activate the oculomotor system, but non-biological cues, like arrows, do not. However, other work has failed to support the claim that gaze cues are special. In the current research we introduced biological and non-biological cues into the anti-saccade task, using a range of stimulus onset asynchronies (SOAs). The anti-saccade task recruits both top-down and bottom-up attentional mechanisms, as occurs in naturalistic saccadic behaviour. In experiment 1 gaze, but not arrows, facilitated saccadic reaction times (SRTs) in the opposite direction to the cues over all SOAs, whereas in experiment 2 directional word cues had no effect on saccades. In experiment 3 finger pointing cues caused reduced SRTs in the opposite direction to the cues at short SOAs. These findings suggest that biological cues automatically recruit the oculomotor system whereas non-biological cues do not. Furthermore, the anti saccade task set appears to facilitate saccadic responses in the opposite direction to the cues. PMID- 22670344 TI - An early history of the Gestalt factors of organisation. AB - Wertheimer's (1923, Psychologische Forschung 4 301 - 350) idea that the perceptual world is articulated according to factors of organisation is widely acknowledged as one of the most original contributions of Gestalt psychology and stands as a milestone in the history of vision research. An inquiry focused on the forerunners of some of Wertheimer's factors of perceptual organisation is documented here. In fact, in 1900 Schumann described grouping by proximity and by vertical symmetry, and in 1903 G E Muller identified the factors of sameness/similarity and contour. Other authors contributed to the early description of these factors, such as Rubin, who in 1922 originally illustrated grouping by similarity. Even though Wertheimer himself granted these authors due recognition, later psychologists have paid little attention to their contributions. Some possible reasons for this negligence are briefly discussed. PMID- 22670345 TI - Independent effects of local and global binocular disparity on the perceived convexity of stereoscopically presented faces in scenes. AB - Evidence suggests that experiencing the hollow-face illusion involves perceptual reversal of the binocular disparities associated with the face even though the rest of the scene appears unchanged. This suggests stereoscopic processing of object shape may be independent of scene-based processing of the layout of objects in depth. We investigated the effects of global scene-based and local object-based disparity on the compellingness of the perceived convexity of the face. We took stereoscopic photographs of people in scenes, and independently reversed the binocular disparities associated with the head and scene. Participants rated perceived convexity of a natural disparity ("convex") or reversed disparity ("concave") face shown either in its original context with reversed or natural disparities or against a black background. Faces with natural disparity were rated as more convincingly convex independent of the background, showing that the local disparities can affect perceived convexity independent of disparities across the rest of the image. However, the apparent convexity of the faces was also greater in natural disparity scenes compared to either a reversed disparity scene or a zero disparity black background. This independent effect of natural scene disparity suggests that the 'solidity' associated with natural scene disparities spread to enhance the perceived convexity of the face itself. Together, these findings suggest that global and local disparity exert independent and additive effects upon the perceived convexity of the face. PMID- 22670346 TI - The role of vision in auditory distance perception. AB - In humans, multisensory interaction is an important strategy for improving the detection of stimuli of different nature and reducing the variability of response. It is known that the presence of visual information affects the auditory perception in the horizontal plane (azimuth), but there are few researches that study the influence of vision in the auditory distance perception. In general, the data obtained from these studies are contradictory and do not completely define the way in which visual cues affect the apparent distance of a sound source. Here psychophysical experiments on auditory distance perception in humans are performed, including and excluding visual cues. The results show that the apparent distance from the source is affected by the presence of visual information and that subjects can store in their memory a representation of the environment that later improves the perception of distance. PMID- 22670347 TI - Development of a 15-item odour discrimination test (Dusseldorf Odour Discrimination Test). AB - A key function of the olfactory system is the detection of differences in odour quality. Therefore, a test was developed to assess odour discrimination ability in normosmic humans. Out of six monomolecular substances (capric acid, coumarin, eugenol, geraniol, phenylethyl alcohol, and vanillin) quaternary mixtures were prepared. Within one item, three odour mixtures were presented (triangle forced choice procedure). The deviant odour contained the same substances as the two remaining odours; however, the proportions were changed. Study 1 (120 participants) aimed to select items that contribute to a high internal consistency. Study 2 (104 participants) assessed test-retest reliability, parallel test reliability and test validity. Out of 45 items, a 15-item test (Dusseldorf Odour Discrimination Test, DODT) with an internal consistency of 0.61 and medium item difficulties was prepared. The test-retest reliability of the DODT was 0.66 (test interval = 4 weeks) and the parallel test reliability 0.42. The DODT correlated significantly with the University of Pennsylvania Smell Identification Test and to a lesser extent with the phenylethyl alcohol odour threshold test. As the DODT did not correlate with the odour discrimination test of the Sniffin' Sticks, the two tests seem to measure different performances of the olfactory system. PMID- 22670348 TI - Tactile perception of nonpainful unpleasantness in relation to perceived roughness: effects of inter-element spacing and speed of relative motion of rigid 2-D raised-dot patterns at two body loci. AB - Rigid surfaces consisting of spatially jittered 2-D raised-dot patterns with different inter-element spacings were moved back and forth across the skin at three different speeds (10-fold range). Within each psychophysical experiment, participants numerically estimated the perceived magnitude of either unpleasantness (nonpainful) or roughness of 2-D raised-dot surfaces applied to two stationary body sites (experiment 1: fingers; experiment 2: forearm). The psychophysical functions for the two types of perceptual judgment were highly similar at both body loci; more specifically, the perceived magnitude of unpleasantness and roughness both increased monotonically as a power function of increasing inter-element spacing, with the rate of growth declining at the upper end of the continuum. These results suggest that inter-element spacing is a critical determinant of the perceived magnitude of unpleasantness (nonpainful), as well as of roughness. Each perceptual judgment also increased as a function of increasing relative speed at both body loci. However, the magnitude of this effect was significantly greater for perceived unpleasantness than for perceived roughness; conversely, the speed effect was significantly greater on the forearm than on the fingers. Several possible explanations for these findings are considered. PMID- 22670349 TI - The effect of contour closure on shape recognition. AB - Recent research on the Gestalt principle of closure has focused on how the presence of closure affects the ability to detect contours hidden in cluttered visual arrays. Some of the earliest research on closure, however, dealt with encoding and recognizing closed and open shapes, rather than detection. This research re-addresses the relation between closure and shape memory, focusing on how contour closure affects the ability to learn to recognize novel contour shapes. Of particular interest is whether closed contour shapes are easier to learn to recognize and, if so, whether this benefit is due to better encoding of closed contour shapes or easier comparison of closed contour shapes to already learned shapes. The results show that closed contours are indeed easier to recognize and, further, that this advantage appears to be related to better encoding. PMID- 22670350 TI - Are the responses generated during a psychophysical task independent of previously presented stimuli or do they depend on earlier stimulus presentations? AB - Quinn and Watt (2006 Perception 35 267-280) showed that the optimal tempi for pieces of music (ie the appropriate speed for a melody) vary from melody to melody. The current study tested if such tempi responses depend on previous stimulus presentations. To do this, we ran a many-participants single presentation version of the Quinn and Watt experiment. 616 visitors to the Glasgow Science Centre participated. We found that the results substantially matched those obtained earlier, and demonstrate that participants' responses are essentially independent of previously presented stimuli. PMID- 22670351 TI - The tilted Hermann grid illusion: 'illusory spots' versus 'phantom bands'. AB - The Hermann grid illusion became a cause celebre, when it was reported that small figural changes from straight to curved bars abolish the dark illusory spots. We demonstrate that this is not an all-or-none effect; rather, the visual system tolerates some tilt/curviness. We transformed straight and curved Hermann grids to rhombic Motokawa grids by gradually tilting the horizontal bars. Initially, we observed only dark illusory spots, then dark spots combined with phantom bands traversing the rhomb along the minor axis, and finally dark phantom bands only. This shows that two kinds of illusions can coexist in the same grid pattern. PMID- 22670352 TI - Healin' groovy: movement affects the appearance of the healing grid illusion. AB - Vection alters the perception of a visual illusion. It enhances the illusory completion of the healing grid (Kanai, 2005, Best Illusion of the Year Contest, Vision Sciences Society). When we perceive our self-motion, the mode of vision is different from that of when we are stationary. PMID- 22670353 TI - How long is your arm? Using multisensory illusions to modify body image from the third person perspective. AB - Updating body representations from the 3rd person perspectives (3PP) seems to require viewing the real body, unlike when viewing from a 1st person perspective. Here, 3PP updating was investigated through induction of a physically impossible multisensory illusion in which participants viewed real-time 3PP video of themselves having their arm pulled until it stretched to twice its normal length. The illusion elicited the subjective experience that the participant's own arm had been stretched and caused an overestimation of reaching distance, although actual reaches were unaffected. Multisensory illusions from the 3PP can alter body image when applied to real bodies. PMID- 22670354 TI - Persistent polyclonal B-cell lymphocytosis in chronic smokers: more than meets the eye. AB - BACKGROUND: Persistent neutrophiliais awell-recognized phenomenon in some chronic cigarette smokers. In contrast, persistent polyclonal B-cell lymphocytosis (PPBL) is considered a rare entity affecting this patient population. METHODS: We analyzed a cohort of 21 patients with chronic smoking histories presenting with persistent leukocytosis. None of the patients was on steroids, lithium preparations, or other medications known to increase the white blood cell (WBC) counts. We excluded any myeloproliferative or lymphoproliferative conditions in our patient cohort. WBC differential was obtained during repeated visits and the mean values calculated. The results were subsequently compared to known upper normal limits and tested for statistical significance. RESULTS: The absolute leukocyte count in our cohort was 17.8 +/- 3.2 x 10(9)/L and the absolute neutrophil count was 12.0 +/- 2.8 x 10(9)/L. The difference proved statistically significant for both values when compared to upper normal limits (P < 0.001). Six patients (five females and one male) were also found to have a significant and persistent lymphocytosis at 5.1 +/- 0.5 x 10(9)/L (P < 0.001). CONCLUSIONS: We have identified the presence of -29% PPBL cases in a series of consecutive patients with persistent leukocytosis/neutrophilia related to chronic cigarette smoking. Similar to the results obtained by other investigators, our PPBL patients showed a younger female predominance. Given the findings in our cohort, we believe that PPBL might be more common than previously thought and discuss further its potential implications for general and specialty practice. PMID- 22670355 TI - Midaortic syndrome in a premature infant. AB - Hypertension is an unusual finding in premature infants and warrants an extensive workup. Well-known causes of hypertension include endocrine, renal and cardiac anomalies. Coarctation of the thoracic aorta, a well-recognized cardiac anomaly leading to hypertension can manifest at various ages including the newborn period. In contrast, midaortic syndrome (MAS), also known as midaortic dysplastic syndrome, is a rare clinical syndrome involving hypoplasia of the abdominal aorta (AA) 1 with varying degrees of narrowing of the visceral branches, often presenting as intractable hypertension. Though there are case reports describing this condition in older children and adults, the diagnosis of MAS can be extremely difficult in neonates, especially in preterm low-birth-weight infants. We describe a rare case of a premature infant who presented with congestive heart failure in utero and intractable hypertension postnatally. This is the youngest reported case of MAS with autopsy confirmation in the literature. PMID- 22670356 TI - Superior vena cava syndrome caused by colon adenocarcinoma metastasis: a case report and review of literature. AB - Superior vena cava (SVC) syndrome is a critical medical condition that usually results from compression of the SVC by an intrathoracic mass. The majority of contemporary etiology of SVC syndrome are related to mediastinal malignancies and/or to the presence of intravascular devices. Rarely, SVC syndrome has been associated with intraluminal metastasis to this vessel. We describe an unusual case of an 88-year-old woman with stage IIA colon carcinoma diagnosed seven years earlier that was treated with surgical resection, who presented with classical signs and symptoms of SVC syndrome. Imaging studies confirmed the presence of an extensive mass in the SVC and intravascular biopsies showed metastatic colon cancer. She was treated with palliative radiotherapy with good clinical response, remaining asymptomatic eight months after the documentation of metastatic disease. To our knowledge this is the second published case of colorectal adenocarcinoma with intravascular metastasis to the superior vena cava causing SVC syndrome. We discuss the different etiologies and management of this syndrome, and encourage physicians to consider intraluminal metastasis as one of the etiologies. PMID- 22670357 TI - An uncommon twist on Twiddler's syndrome. AB - Twiddler's syndrome is a rare cause of pacemaker dysfunction characterized by coiling of the lead around the rotated generator. It is even less common for implantable cardioverter-defibrillator (ICD) devices. We describe a 44-year-old woman who underwent successful implantation of an ICD and three months later presented with left arm twitching. Chest radiograph demonstrated the unusual dislodgement of the atrial lead only and rotation of the ICD generator. The diagnosis of Twiddler's syndrome with solitary atrial lead rotation was thus established. The ICD pacing mode was switched to VVI, which resulted in cessation of muscle contractions. She later underwent atrial lead revision, untwisting and reanchoring of the ICD generator without any complications. PMID- 22670358 TI - Telemedicine-based digital retinal imaging vs standard ophthalmologic evaluation for the assessment of diabetic retinopathy. AB - OBJECTIVE: To study the cost benefit analysis of using a telemedicine-based digital retinal imaging evaluation compared to conventional ophthalmologic fundus examination of diabetic patients for diabetic retinopathy. METHODS: In this study, diabetic patients from Community Health Center, Inc. (CHCI), a large multi site Federally Qualified Health Center) were evaluated by teleophthalmology using the Canon CR-1 nonmydriatic fundus camera. Digital images were acquired in the CHCI offices and saved on the EyePACS server network. The images were later evaluated by retinal specialists at the Yale Eye Center, Yale University Department of Ophthalmology and Visual Science. The costs for the standard of care ophthalmic examinations were calculated based on 2009 Medicaid reimbursement rates. The process of telemedicine-based diagnosis was based on a take-store forward-visualize system. The cost of telemedicine-based digital retinal imaging examination included cost for devices, training, annual costs and a transportation fee. Current Medicaid reimbursement, transportation, and staff labor costs were used to calculate the conventional retinal examination cost as a comparison. RESULTS: Among the 611 patients digital retinal images screened in the first year of this program and for whom data are available, 166 (27.2%) cases of diabetic retinopathy were identified. Seventy-five (12.3%) patients screened positive with clinically significant disease and were referred for further ophthalmological evaluation and treatment. The primary direct cost of the telemedicine was $3.80, $15.00, $17.60, $1.50, and $2.50 per patient for medical assistant, ophthalmologist, capital cost (Equipment + Training), equipment maintenance, and transportation fee, respectively. The total cost in the telemedicine-based digital retinal imaging and evaluation was $40.40. The cost of conventional retinal examination was $8.70, $65.30, and $3.80 per patients for round-trip transportation, 2009 national Medicaid Physician Fee Schedule allowable for bilateral eye examination, and medical assistant personnel, respectively. The total costs of conventional fundus examination were $77.80. An additional conventional ophthalmologic retinal examination was required for 75 (12.3%) patients with clinically significant disease on telemedicine evaluation, which involves an averaged additional cost of $ 9.55 per patient for all the patients in the study. If the cost of subsequent examination was added, the total cost of telemedicine-based digital fundus imaging was $49.95 per patient in our group of 611 patients evaluated. CONCLUSIONS: Our cost analysis indicates that telemedicine-based diabetic retinopathy screening cost less ($49.95 vs $77.80) than conventional retinal examination and the telemedicine-based digital retinal imaging examination has the potential to provide an alternative method with greater convenience and access for the remote and indigent populations. Diabetes mellitus and diabetic retinopathy are growing problems in the United States and worldwide. Large scale adoption of telemedicine should be encouraged as a means toward providing improved access, increasing compliance with annual evaluation, at a low cost for patients with diabetes with direct access to an eye care specialist. PMID- 22670359 TI - Surveillance of adverse drug events in a large tertiary-care hospital. PMID- 22670360 TI - The ebb and flow model: a philosophy of organizational learning in the academic health center. AB - Academic health centers (AHCs) have traditionally been a vibrant locale for cutting-edge medical research, androgogic education and innovative clinical care for the most vexing diseases. While these pursuits have coexisted and flourished, the realities of the health-care business environment have demanded reformatting and emulation of a corporate organizational model. This evolution has impacted the core identities of the AHC and challenged individual medical-educators, clinician-scientists and basic science investigators to persist and succeed in this milieu. The AHC has a unique capacity to muster the innate learning drive of these individuals into an organizational mission as it balances the pressures exerted from both the internal and external environments. The AHC as an organization can be viewed as an experimental condition with modifiable variables to which its professionals can react, adapt to, and transform. Organizational learning and change implementation is in essence an experiment in human behavior modification. While all individuals are subject to change, merely assembling them in a single locale determines neither a predictable homogeneous outcome nor the success of their endeavor. This article highlights some of these propositions and offers a philosophical approach to advance the AHC as an organization through the creativity and innovation of its professional ranks. PMID- 22670362 TI - Self-governing organized medical staff. PMID- 22670361 TI - Is Social Security medicine necessary? 1962. PMID- 22670363 TI - FDR, HST, JFK, LBJ, SGR. PMID- 22670364 TI - Perspectives: the education of advanced practice nurses. PMID- 22670365 TI - Connecticut without connectivity. PMID- 22670366 TI - The impact of OIG's work plan on medical practices. PMID- 22670367 TI - Questioning the validity, methodology, cost and effectiveness of recredentialling: it's about time. PMID- 22670368 TI - Communicate, Communicate, communicate. PMID- 22670370 TI - Coming up with the goods. PMID- 22670369 TI - Azole tolerance test: a bedside observation to enhance physical diagnosis of superficial fungal infection. PMID- 22670371 TI - International network pushes the case for children's nursing. PMID- 22670372 TI - Sure Start was bound to fail. PMID- 22670373 TI - Where do our priorities lie? PMID- 22670374 TI - Drama of the NHS. PMID- 22670375 TI - Consulting children and young people on what makes a good nurse. AB - Health and education agencies collaborated in a hospital's special school to ask children what made a 'good' nurse. Eleven children aged between 11 and 14 years took part and described the 'good' nurse as having a professional persona and the ability to connect with them, delivering timely and effective care and being respectful of children's dignity. The results are now being used in an undergraduate children's nursing curriculum. PMID- 22670376 TI - Use of checking systems in medicines administration with children and young people. AB - This study aimed to establish which policies are in place for checking medication administration in UK children's units and to discuss evidence to support the use of different checking processes. It involved a questionnaire survey (n=105) in 69 UK hospitals of children's nurses and pharmacists. In the hospitals surveyed, most administrations of oral and intravenous medications were checked by two registered children's nurses. Evidence suggests a role for single and double checking depending on risk assessment. Robust research is needed to further evaluate these processes. PMID- 22670377 TI - Caring for a child with asthma: pre-registration education. AB - Management abilities enhance the care delivered to patients in the NHS. Students need to acquire these competencies to meet the Nursing and Midwifery Council requirements at registration. This article explores the management skills used by a third-year child branch nursing student in the assessment and care of a child with acute asthma in a paediatric emergency department. PMID- 22670378 TI - Assessment and management of a child with suspected acute neck injury. AB - Any child presenting at an emergency department after trauma, such as road traffic accidents, falls, sports and head injuries, should be assessed for risk of injury to the cervical spine. The aim of this article is to provide an overview of the assessment and nursing management of a child with a suspected cervical spine injury. Basic anatomy is covered along with neck injury assessment, how to measure a cervical collar correctly, safe immobilisation, and communication. PMID- 22670379 TI - [Tolstoi and his model of care]. PMID- 22670380 TI - [Absence of nursing in the multidisciplinary team of social projects]. PMID- 22670381 TI - [Generic drugs: we must cut pharmaceutical spending but undertaking drug quality]. AB - The World Health Organization and all drug regulatory agencies (DRA) support the commercialization of generic medicines because they control costs and are irreplaceable therapeutic options in countries lacking the innovator product. Generic drugs are widely considered to be cost-efficient substitutes for brand name medications. They make up about 20% of the total number of prescriptions in Spain, a figure that is still far from the use of generic drugs in USA and other European countries. Despite economical interest in this issue, in this article we review the interest of generic drugs from a pharmacological and clinical perspective that must undertake drug quality to ensure drug efficacy and safety of the patients. A generic drug (generic drugs, short: generics) is defined as "a drug product that is comparable to brand/reference listed drug product in dosage form, strength, route of administration, quality and performance characteristics, and intended use". Both the reference drug and the generic drug have to demonstrate previously they are therapeutically equivalent. With the exception of parenteral drugs, two products have demonstrated to be therapeutically equivalent if after administration in the same molar dose, their effects with respect to both efficacy and safety are essentially the same, as determined from bioequivalence studies in terms of comparison of appropriate pharmacokinetic parameters and bioavailability. Parenteral formulations, however, are not required to demonstrate therapeutic equivalence because it may be considered self evident. Such assumptions have never been challenged, but there are reasons to do so for parenteral antimicrobials. It is interesting to highlight that although brand-name drugs and generic drugs are both approved by DRA and may be interchangeable with respect to their clinical effects, they can differ substantially in their appearance. Consumers of brand-name medications receive identical-appearing batches of pills with each refill, whereas consumers of generic drugs must be prepared to receive pills of a different size, color, and shape, depending on which manufacturer is supplying their pharmacies. PMID- 22670382 TI - [Research projects in mental health care speciality: mentoring and lived experiences]. AB - The goal of the present study is to describe the methodology followed in the implementation of the mentoring research projects developed by the three residents of mental health during the 2009-10 academic years and present the results obtained and recognition. We designed eight targeted monthly tutorials and educational material complementing the methodological support. The development of the project followed an established pattern that allowed progressively advancing in the various phases. When completed the projects, the most relevant were selected for presentation at the XI National Meeting of Residents of Mental Health Nursing, and planned a public presentation of all projects. The main findings from the evaluation work were made for every resident of the experience and the quality of the tutorials. In his narrative are the positive enrichment achieved during the year of residency from the perspective of learning as well as relationship with mentors. In the individual assessment reflect relevant aspects of the authorization process as closeness, trust, resolving doubts, guidelines for intervention. The project presented at the national meeting took second award. PMID- 22670383 TI - [Crisis and nurses]. AB - Nobody can escape that we are in crisis. Already are responsible every day media, risk agencies and abstract but crucial markets reminded us. In this crisis, deep, prolonged and distressing health systems have been in the spotlight of national Governments and corporations, as key elements of building and resolution of the crisis. Generation because it interprets its inefficiency is responsible for much of the crisis. Resolution because it is understood that actions that envelope the same are carried out they shall foster the output. So then we have two key elements: crisis and health systems, which combine very differently but which inevitably and unfortunately have been associated on a permanent basis. To understand this symbiosis and try to analyze it I operate the simple formula of semantically understanding what is crisis and what health crisis. PMID- 22670384 TI - [Hospitalized children's parents' anxiety in critical care units]. AB - Child hospitalization is a potentially stressful process that affects both patients and family members. OBJECTIVE: Describe the anxiety that the parents of admitted children at a Intensive Care Units, Pediatric (PICU) and/or Neonatal (NICU) during the first week of hospitalization. MATERIAL AND METHOD: Observational study descriptive, transversal conducted at the Gregorio Maranon Hospital, in PICU and NICU. The inclusion criteria were: patients who didn't exceed the week admitted but they were at hospital more than one day, patients whose therapeutic effort wasn't limited and spanish-speaker parents. The sample size was 60 parents. We designed a questionnaire to measure sociodemographic variables and others related with the social support. The resulting variable, anxiety like State Anxiety (SA) and Trait Anxiety (TA) were determined by the STAI inventory. RESULTS: All the parents showed anxiety the average females SA was 44.59 (+/- 8.02) while the average of men was 44.32 (+/- 6.69). The results show a TA average of 34.73 (+/- 4.09) in woman and 34.95 (+/- 4.93) in men. 83% of the parents of the sample participated in their child caring, having this variable relationship with level of SA (p<0.05). Moreover 98% of parents understood the information given and were satisfied with it. CONCLUSION: All the parents presented anxiety, both SA and TA. They felt informed and supported by nurse. All these actions are directed towards an integral attention taking into account the family as the unit. PMID- 22670385 TI - [Global posturology as method of health self-regulation]. PMID- 22670386 TI - [Descriptive study of intrapartum antibiotic prophylaxis of neonatal infection by group B Streptococcus in Txagorritxu]. AB - INTRODUCTION: GBS is one of the most important causes of neonatal sepsis of vertical transmission (1-2% of the carriers). The infection may involve newborn's death or severe complications. The culture of vaginal and rectal GBS is a screening test and it is performed to all pregnant women between 35-37 weeks of gestation. If it is positive, intrapartum penicillin is prescribed. If it is negative or unknown, the antibiotic per protocol is given according to risk factors: rupture of membranes more than 18 hours, intrapartum temperature, or prematurity. The aim of this study is to quantify women who receive intrapartum antibiotic in relation to the positive culture and achievement with the SEGO's recommendation. MATERIAL AND METHODS: It describes a sample of 261 women of the Txagorritxu Hospital who have given birth during the work shift of researchers, excluding cesarean sections. VARIABLES: results of culture, antibiotic administration. Data were collected by reviewing and analyzed medical records using SPSS 17.0. RESULTS: From 261 women, 69 (26.4%) received antibiotic administration. From 69, 46 (66.67%) had a positive culture. 26 (37.68%) received antibiotics according to risk factors, although their cultures were negative or unknown. DISCUSSION: The results suggest there is a correct application of the SEGO's recommendation. Carrier women with no risk factors would not have received antibiotic therapy without screening. PMID- 22670387 TI - [The climacteric and biomedicine: reflections from nursing and the sociology of health and illness disciplines]. AB - This article critically examines the biomedical model and how it has influenced the social construction of the meaning of the menopause. This model has been criticized as reductionist since it understands people as entities made of several parts that can be studied separately. Contrarily for nursing, people are formed by several parts in direct relation with the environment and themselves. Therefore, it is not posible to understand people's reality without considering social factors. The menopause has been described in various biomedical texts as a phenomenon similar to a disease, with severe symptoms and negative connotations. However the experiences and meanings that women ascribe to this stage of their life are varied and not always negative. In order to offer appropriate care, it is important for nursing to think about the role of social interaction in constructing the meaning individuals attribute to phenomena. PMID- 22670388 TI - [Cell saver]. AB - The blood retrievers are instruments increasingly used in operating rooms. They are especially useful in operations where there is a high risk of bleeding and transfusion requirements are high. In paediatrics is of great importance in complex interventions in order to avoid allogeneic transfusion (blood collected from donors). The implementation of the recovery of blood in the surgical field is very simple and easy to use. This is a suction tube that collects the blood that is free, transferring it to a centrifuge where it is filtered and washed, stored in a blood collection bag for subsequent infusion. The blood is of high quality and contains a high hematocrit blood from the bank. PMID- 22670389 TI - [Nursing diagnoses linked to immigration process]. AB - The migration population's new social and demographic reality require a need's analysis. The migration's challenges demand an urgent reflection on all disciplines of an interdisciplinary team. Nursing's Language defines nursing's contribution. Nursing's language includes Outcomes, Interventions and Diagnosis. It is necessary to reflect on theory and research. There is little research to connect Nursing Diagnosis with the migration phenomenon The objective is to identify Nursing Diagnosis related to the migratory process by bibliographic revision and the hypothesis is Nursing diagnosis does not describe the whole migration phenomenon. 32 Nursing Diagnosis could be found in 12 documents of methasintesis. There are a lot of nursing's diagnosis and reflection according to the OPT (Outcome-Present State-Test) model. Clinical Reasoning Web shows 11 nursing's diagnosis related to migratory process. Risk or Relocation Stress Syndrome describes better the answers to the migratory process. PMID- 22670390 TI - [If by the end of the day we saw in a dish all we have ingested, we would be surprised. Interview by Maria Jesus Nadal Nadal]. PMID- 22670391 TI - [Performance improvement project for the introduction of safety devices: interdisciplinary approach and participation of professionals]. AB - OBJECTIVE: Develop a performance improvement project to introduce safety needle tube holder for venous blood collection after evaluation of the professionals. METHODS: Reach: Costa Ponent Primary Care Direction and the Hospital Viladecans Hospital from Institute Catala de la Salut. METHOD: Create interdisciplinary group. Design in two phases. First, material selection and assessment of safety devices. Second, implementation and evaluation of the proposed performance improvements. The material was selected using standardized criteria on safety devices, suitability to clinical practice and technical compatibility The assessment was qualitative questionnaire by adapting the Centers for Disease Control and Prevention. RESULT: We evaluated three types of needles, two of them were evaluated by 54 primary care professionals and one for 12 professionals from the hospital. Good acceptance regarding their interaction with technology and patient safety. It was considered effective safety device. The overall rating was satisfactory. Underutilized the material by hospital professionals. There were no differences regarding sex, the hand size, experience, training you received, and type of needle. It prepared a proposal to come in progressively safety needle tube holder in primary care. The evaluation performed in the hospital it was considered insufficient. CONCLUSIONS: Interdisciplinary participation is essential to implement measures to safe care. The safety needle evaluated were effective with respect to security professionals and the patient. The involvement of different levels of the organization have developed a proposal for performance improvement adapted to the needs of our environment. PMID- 22670392 TI - [Assess your knowledge on the cicatrization process]. PMID- 22670393 TI - [The European Academy of Nursing Sciences holds a scientific meeting in Barcelona]. PMID- 22670394 TI - Monoarticular arthritis update: Current evidence for diagnosis and treatment in the emergency department. AB - Monoarticular arthritis presentations in the emergency department are increasing as the population ages and gets heavier. Many etiologies--from trauma to infection to autoimmune-mediated inflammation--are associated with significant disability or early mortality, and their treatments are associated with adverse effects. A systematic approach to evaluating patients with monoarticular arthritic complaints is important for relieving pain, diagnosing systemic illness, and unmasking true arthritis emergencies. Septic arthritis is a rapidly destructive process that can cause significant disability in a matter of hours or days, with relatively high mortality. Other causes of monoarticular arthritis may cause disability in the long term. In all cases, accurate diagnosis and appropriate therapies are crucial for resuming activities and preventing long term deficits. This review examines the diagnosis and treatment of monoarticular arthritis, with a focus on recent evidence in the diagnosis of septic arthritis and new research on gout therapies. Modalities for pain control and new techniques for imaging are discussed. PMID- 22670395 TI - Loud music. Our transfer calls can define us. PMID- 22670396 TI - When "everything hurts". A patient in pain requires you to don your detective hat. PMID- 22670397 TI - Fence splitter. Evading police leads to a gruesome testicular injury. PMID- 22670398 TI - Pressing issues. Q&A with D. Randy Kuykendall Interview by Jenifer Goodwin. PMID- 22670399 TI - Toxicology today. Never underestimate the ingenuity of drug users. PMID- 22670400 TI - Lessons learned from the Joplin tornado. What should an EMS system take from such a disaster? PMID- 22670401 TI - Managing sepsis in the adult patient. What you need to know about emerging diagnostic trends and treatments for the sepsis patient. PMID- 22670402 TI - When thinking is hard: managing decision fatigue.. PMID- 22670403 TI - A primer on pediatric diabetic emergencies. What do you do with a hypo- or hyperglycemic child? PMID- 22670404 TI - I protest. Toward a more civil discourse, within and without. PMID- 22670405 TI - Mental health, natural and human-made disasters: lessons learnt and future needs. PMID- 22670406 TI - The great east Japan earthquake in 2011; toward sustainable mental health care system. AB - In face with a triple disaster of earthquake, tsunami and nuclear power plant accident, the degrees of which are historically hardly preceded, immediate mental health countermeasure was taken by the initiative of the national and local government together with academic and clinical organizations. Based on previous experience of natural disasters, more than 50 mental health care teams have been organized and dispatched to the affected areas, scheduled by the Ministry of Health, Labor and Welfare. When 6 months have passed, the acute and temporal support system should be replaced with more sustainable local networks with aims at promoting resilience, though community psychiatric service should be developed as well. Existing guidelines should be respected but actually it tended to be only partially recognized. In Fukushima prefecture, where nuclear plant accident occurred, its mental health impact is most concerned and long-term follow-up of the residents' health has been being planned. PMID- 22670407 TI - The narrative epidemiology of L'Aquila 2009 earthquake. AB - The authors describe their experience working and living in L'Aquila, where at 3.32 a.m., early in the morning of 6 April 2009, a 6.3 Richter magnitude earthquake caused serious damages to this 13th century town (with a population of 72 000 and a health district of 103 788), in the mountainous Abruzzo region and to several medieval hill villages in the surrounding areas: 309 residents were killed, over 1600 were injured, 66 000 residents were displaced, and, the centre of L'Aquila, the main historical and artistic centre of Abruzzo, was totally destroyed. Here is described the work done at the Psychiatric Unit of the General Hospital of L'Aquila and in the University. The Authors report the incidence rate of Acute Stress Disorder (ASD) in help-seekers (full ASD 4.9%, and partial ASD 39.3%), and of post-traumatic stress disorder (PTSD) found in different samples of population (range 12-37.5). The authors express their consideration about which real-world variables can reflect the population distress and the naturalistic process of recovery in such natural disasters. After the earthquake they hypothesize that a lot of residents had found their way to recover through 'writing, telling the story', by analogy with what narrative medicine asserts, thus estimating the positive effect of 'emotional disclosure' on health. A large number of materials (books, web-blogs, videos) were produced by residents and a database of memories was implemented. The suffering and struggle to recover in the aftermaths of a traumatic experience often yields remarkable transformations and positive growth. From this point of view, the authors underline the increased virtual relationships of residents through Facebook, to cope with the loss of previous social relationships, to get information about recreational opportunities, or to get organized for public events, despite their displacement. Many collective demonstrations were organized and showed the will to actively participate to the processes of reconstruction of the civil and scientific life of the town. The authors stress the need to prevent natural disasters, instead of preventing mental disorders following natural disasters, reporting that seven Italian seismologists and scientists are on trial for manslaughter, accused to have failed to evaluate the true risks of L'Aquila earthquake. PMID- 22670408 TI - Are human made disasters different? AB - The author distinguishes natural from human made disasters, and identifies their traumatic effects. He stresses the impact on both individuals and communities. Lessons learned from the NYC World Trade Center bombings are offered. He concludes with a universal prescription for responding to disasters. PMID- 22670409 TI - Heterogeneity: the issue of apples, oranges and fruit pie. AB - Heterogeneity refers to any kind of variation among studies contributing to the same outcome in a systematic review. There are three broad types of heterogeneity: clinical heterogeneity, methodological heterogeneity and statistical heterogeneity. In this paper, we describe these three types of heterogeneity and the main statistical approaches to measure heterogeneity. PMID- 22670410 TI - Functional MRI studies in disruptive behaviour disorders. AB - Aggressive or antisocial behaviours with violations of social rules are the main features of disruptive behaviour disorders (DBDs), which are developmental diseases and include conduct disorder and oppositional defiant disorder. In the last decade, several efforts have been made to shed light on the biological underpinnings of DBDs. In this context, the main findings of functional magnetic resonance imaging studies in DBD are reported here. There are indications of neural dysfunctions in response to affective stimuli, especially regarding medial and orbitofrontal prefrontal cortex and connected subcortical structures. PMID- 22670411 TI - The importance of secondary trauma exposure for post-disaster mental disorder. AB - BACKGROUND: Interventions to treat mental disorders after natural disasters are important both for humanitarian reasons and also for successful post-disaster physical reconstruction that depends on the psychological functioning of the affected population. A major difficulty in developing such interventions, however, is that large between-disaster variation exists in the prevalence of post-disaster mental disorders, making it difficult to estimate need for services in designing interventions without carrying out a post-disaster mental health needs assessment survey. One of the daunting methodological challenges in implementing such surveys is that secondary stressors unique to the disaster often need to be discovered to understand the magnitude, type, and population segments most affected by post-disaster mental disorders. METHODS: This problem is examined in the current commentary by analyzing data from the WHO World Mental Health (WMH) Surveys. We analyze the extent to which people exposed to natural disasters throughout the world also experienced secondary stressors and the extent to which the mental disorders associated with disasters were more proximally due to these secondary stressors than to the disasters themselves. RESULTS. Lifetime exposure to natural disasters was found to be high across countries (4.4-7.5%). 10.7-11.4% of those exposed to natural disasters reported the occurrence of other related stressors (e.g. death of a loved one and destruction of property). A monotonic relationship was found between the number of additional stressors and the subsequent onset of mental disorders CONCLUSIONS. These results document the importance of secondary stressors in accounting for the effects of natural disasters on mental disorders. Implications for intervention planning are discussed. PMID- 22670412 TI - Age of onset of mental disorders and use of mental health services: needs, opportunities and obstacles. AB - PURPOSE OF REVIEW: In this review, we provide an update of recent studies on the age of onset (AOO) of the major mental disorders, with a special focus on the availability and use of services providing prevention and early intervention. RECENT FINDINGS: The studies reviewed here confirm previous reports on the AOO of the major mental disorders. Although the behaviour disorders and specific anxiety disorders emerge during childhood, most of the high-prevalence disorders (mood, anxiety and substance use) emerge during adolescence and early adulthood, as do the psychotic disorders. Early AOO has been shown to be associated with a longer duration of untreated illness, and poorer clinical and functional outcomes. SUMMARY: Although the onset of most mental disorders usually occurs during the first three decades of life, effective treatment is typically not initiated until a number of years later. There is increasing evidence that intervention during the early stages of disorder may help reduce the severity and/or the persistence of the initial or primary disorder, and prevent secondary disorders. However, additional research is needed on effective interventions in early-stage cases, as well as on the long-term effects of early intervention, and for an appropriate service design for those with emerging mental disorders. This will mean not only the strengthening and re-engineering of existing systems, but is also crucial the construction of new streams of care for young people in transition to adulthood. PMID- 22670413 TI - No time to lose: onset and treatment delay for mental disorders. PMID- 22670414 TI - What promotes and inhibits cooperation in mental health care across disciplines, services and service sectors? A qualitative study. AB - AIMS: To explore the practice of cooperation in mental health care across services and identify conditions that promote and inhibit cooperation. METHODS: Focus groups with relevant service providers were conducted in four exemplary regions in Germany (rural/ urban and East/West). The discussions were content analysed. RESULTS: Seven central categories were deduced: (1) involved service providers, (2) comprehension, (3) reasons, (4) instruments for cooperation, (5) promoting and inhibiting conditions, (6) interdisciplinarity, and (7) regional and personal networks. Cooperation is practiced in networks, rather than defined relations. Who is involved in cooperation depends on patients/clients needs and may vary from case to case. Service providers do not have theoretical concepts of cooperation. Cooperation relies not only on personal contacts and knowledge between services but also on time, financial reimbursement and the social capital of the environment. In particular, cooperation with physicians was considered to be difficult by non-medical professionals. Physician's role models do not seem to include cooperation with other disciplines as a core task. CONCLUSIONS: To improve cooperation, regional and sustainable mental health networks have to be systematically implemented by providing leadership, time and reimbursement for network meetings. Interdisciplinary cooperation practice should be part of the curricula of medical students and residents in psychiatry. PMID- 22670415 TI - Gender differences in public beliefs and attitudes about mental disorder in western countries: a systematic review of population studies. AB - AIMS: While quite a number of theories and hypotheses about gender differences in public beliefs and attitudes about mental illness have been proposed, the empirical evidence, particularly evidence based on population studies, is rather scarce. METHODS: A systematic review of population-based studies providing information on gender differences in beliefs about mental disorders and attitudes towards the mentally ill was carried out. RESULTS: While both genders are no different in their willingness to seek informal help for mental illness, women seem more ready to recommend professional help than men. They also evaluate treatment outcomes more favourably. Women are more likely to endorse psychosocial conceptualizations of mental illness than men, and, in consequence, are more in favour of psychotherapy. With a few exceptions, women do not seem to display more favourable attitudes than men towards people with mental disorder. Female patients seem to be rejected by the public less than male patients. CONCLUSIONS: Our review suggests that gender matters in public beliefs and attitudes about mental illness. Some theoretical assumptions are supported by empirical findings, others not. However, as evidence is rather scarce, further studies testing theory driven hypotheses are needed. PMID- 22670416 TI - The relationship between socio-economic status and antidepressant prescription: a longitudinal survey and register study of young adults. AB - AIMS: The current study examines the relationship between socio-economic status (SES) and antidepressant prescription among young adults and investigates mechanisms that could explain such a potential social gradient. METHODS: Longitudinal survey data from a population-based Norwegian sample (N = 2606) was collected in four waves over a 13-year period. The data were linked to register data on antidepressant prescription and several indicators of SES (education, income, social or unemployment benefits, disability or rehabilitation benefits and parents' education). RESULTS: Apart from parents' education, all indicators of low SES were related to higher rates of antidepressant prescription. A part of the relationship between SES and antidepressant prescription was due to low SES being related to higher levels of anxiety and depression. Moreover, low SES was related to more frequent use of mental health services, which again was related to higher rates of antidepressant prescription. Both contact with physicians and other mental healthcare professionals accounted for some of the relationship between SES and antidepressant prescription. CONCLUSIONS: The study provides information about mechanisms involved in the relationship between low SES and antidepressant prescription. More research is needed about whether a comparable social gradient in antidepressant prescription is also to be found outside the Nordic countries. PMID- 22670417 TI - Personalised support delivered by support workers for people with severe and persistent mental illness: a systematic review of patient outcomes. AB - AIMS: Personalised support services assist patients with severe and persistent mental illness (SPMI) to live with functional deficits by providing living skills, emotional support, community access and advocacy. This paper aims to systematically review the evidence for personalised support. METHODS: Systematic searches of Medline, PsycINFO and Google Scholar (inception to March 2011) identified studies investigating patient outcomes for personalised support services. The quality of the selected studies was assessed. The strength of evidence for the three categories of patient outcomes (illness acuity, personal functioning and patient satisfaction) was graded. RESULTS: Fifteen studies met inclusion criteria with most rated as having moderate or weak study designs. The selected studies evaluated programs for outpatients with SPMI. There was moderate strength of evidence for reducing illness acuity and improving patient satisfaction with services, and weak strength of evidence for improving personal functioning in studies published to date. Most programs delivered multiple service types, and no clear pattern of service types leading to specific patient outcomes could be discerned. CONCLUSIONS: Although evidence published to date for personalised support is of variable quality, it suggests that services may be effective. More research on the effects of personalised support subtypes on patient outcomes is required. PMID- 22670418 TI - Childhood depression and anxiety disorders in Serbia: a psychometric study of four screening questionnaires. PMID- 22670419 TI - Parents' beliefs about actions they can take to prevent depressive disorders in young people: results from an Australian national survey. PMID- 22670420 TI - Social media and nursing. PMID- 22670421 TI - Social media and professional nursing: friend or foe? PMID- 22670422 TI - Sharon Starr: an exemplar in public health nursing. PMID- 22670423 TI - Environmental Public Health Tracking Program. PMID- 22670425 TI - Healing through compassionate care. PMID- 22670424 TI - Strengthening your social networking skills. PMID- 22670426 TI - Reaching out to friends and family. PMID- 22670427 TI - Safety at the One World Trade Center project. PMID- 22670428 TI - Listen up: training older workers. PMID- 22670429 TI - Beating the heat (and humidity). PMID- 22670430 TI - No shortcuts. PMID- 22670431 TI - The whole package. PMID- 22670433 TI - Hands off 274(j)! PMID- 22670432 TI - Instituting comprehensive risk management. PMID- 22670434 TI - Motivating and promoting safety. PMID- 22670435 TI - Eliminating silos at Airgas. PMID- 22670436 TI - Grainger moves fast on mobile. PMID- 22670437 TI - Beyond SDS compliance. PMID- 22670438 TI - How much does feedback help? PMID- 22670439 TI - Stop saying safety is first. PMID- 22670440 TI - Leadership alchemy. PMID- 22670441 TI - [Image of the month. Tophaceous gout of the forefoot ]. PMID- 22670442 TI - [How I treat ... dyslipidemia according to the cardiovascular risk profile]. AB - The new guidelines from the European Atherosclerosis Society and the European Society of Cardiology include a number of new items. Here we demonstrate their application in several different clinical examples. We focus on the 4 items most pertinent for medical practice: 1) the stratification of risk of cardiovascular disease into 4 categories ('very high', 'high', 'moderate' and 'low risk'), involving--for primary prevention cases--the use of the SCORE table, which has been calibrated for Belgium and where the risk can be adjusted according to HDL cholesterol and the presence of other risk factors; 2) the choice of more stringent therapeutic targets for LDL cholesterol (< 70 mg/dl for 'very high' risk patients, 100 mg/dl for 'high' risk patients and 115 mg/dl for patients at 'moderate' risk); 3) the choice of other therapeutic targets (non-HDL cholesterol and apolipoprotein B levels) for patients at 'very high' or 'high' risk with combined dyslipidaemia; and 4) follow-up of lipid parameters and muscular and hepatic enzymatic profiles. PMID- 22670443 TI - [Clinical case of the month. Cardiac complications of acromegaly: a rare cause of dilated cardiomyopathy]. AB - Acromegaly is a disease characterized by chronic growth hormone hypersecretion. Cardiovascular complications represent the main cause of death. We present here a rare case of dilated cardiomyopathy whose diagnosis revealed an acromegaly. This will provide the opportunity to review an uncommon disease and its recently reassessed prevalence. PMID- 22670444 TI - [Screening strategy and diagnostic criteria for gestational diabetes. Proposals of the GGOLFB]. AB - For nearly 50 years, the strategy of screening and the diagnostic criteria for gestational diabetes have been the subject of endless controversies. They differ between countries and from one center to another, mainly because of the lack of hard data allowing to define glycemic thresholds at which a therapeutic management is needed. Recently, a large observational study has demonstrated the existence of a robust relationship between maternal blood sugar and several fetomaternal perinatal complications. This relationship is linear, with no clear threshold that would define gestational diabetes unambiguously. Meanwhile, two randomized intervention trials have shown that the therapeutic management of mild gestational diabetes was associated with improved perinatal outcomes. Based on these data, the "International Association of Diabetes and Pregnancy Study Group" (IADPSG) released new recommendations on screening methods and diagnostic criteria for gestational diabetes. Although already endorsed by several international associations and implemented in some countries, these recommendations still raise questions and criticisms. This is why the "Groupement des Gynecologues Obstetriciens de Langue Francaise de Belgique" (GGOLFB) organized a meeting between diabetologists and gynecologists which allowed to reach a consensus on the strategy that we intend to implement in our respective centers. The purpose of this paper is to briefly overview the recent advances in gestational diabetes and more particularly to make our key conclusions known to the medical community. This will enable the standardization of the management of gestational diabetes in the French-speaking part of Belgium. PMID- 22670445 TI - [Neuroprotection by controlled hypothermia in neonatal hypoxic-ischemic encephalopathy]. AB - Neonatal hypoxic-ischemic encephalopathy is a major cause of death and neurodevelopmental delay. Brain cooling by mild controlled hypothermia is currently the most promising therapy. PMID- 22670446 TI - [Staphylococcus and its counter-measures against epidermal antimicrobial peptides]. AB - Staphylococci are microorganisms often involved in a colonization process on muco cutaneous sites. They are responsible for various nosocomial and community associated skin infections. The methicillin-resistant staphylococci are particularly involved in various aspects of pathology. Epidermal antimicrobial peptides are part of the host defense mechanisms corresponding to the innate immunity. They may limit the extent in colonization. However, some staphylococci are able to bypass the antimicrobial peptides released by the host. PMID- 22670447 TI - [Stress and smoking in treatment-seeking smokers]. AB - Fear of not controlling stress is the most frequently reported obstacle to smoking cessation. We report a retrospective study involving 70 smokers whose files were randomly selected from a smoking cessation clinic's recruitment. Stress management as a motive to smoke (SMMS) was systematically explored at the first visit, before quit date. SMMS mean score was 7.36 (+/- 2.4) on a 10 point scale. The score was higher in females than in males (p = 0,048). A multivariate logistic regression showed that SMMS was explained by two variables: physical dependence as measured with the FTND score (OR = 1.7, 95% CI = 1.18-2.46), and anxiety as measured with the HAD scale (OR = 1.27, 95% CI = 1.03-1.56). In conclusion, the high frequency and impact of perceived stress on smoking behavior call for a systematic clinical evaluation of perceived stress when engaging a treatment for smoking dependence. Our work has confirmed the importance for the smokers of perceived stress on their smoking behavior, particularly in females. Perceived stress showed a strong relationship with nicotine dependence and anxiety. Further investigation is warranted for a better understanding of the relationship between perceived stress and anxiety in smokers. PMID- 22670448 TI - [Medication of the month. Febuxostat (Adenuric)]. AB - Gout is a rheumatologic disease due to the deposition of urate (the catabolite of purines) crystals within joints. Prevalence of the disease is high. Potential articular and nephrological complications are numerous. Therefore, a chronic, preventive and effective therapy is required in specific patients. Dietary changes are frequently insufficient and urate-lowering therapy is thus necessary, like uricosuric or xanthine oxydase inhibitors. The objective of these therapies is to lower serum urate levels below 6 mg/dL. The xanthine oxydase inhibitor allopurinol is still the most used in the context of gout prevention. However, allopurinol tolerance and efficacy are far from optimal. Now, a new therapy is available in Belgium, the febuxostat. Febuxostat is a new xanthine oxidase inhibitor.Tolerance and therapeutic effect seem better compared to allopurinol. In this article, we review pharmacological data about this new treatment. We also review the most important clinical trials underlining strengths and limitations of febuxostat. PMID- 22670449 TI - [Clinical vignette for the medical school student: jugular foramen syndrome]. AB - Cranial neuropathies are frequent and their semiological analysis is the basis of the diagnostic workup. This is even more true in the case of multiple cranial neuropathies. We here propose a diagnostic exercise in the case of a simultaneous cranial nerves IX (glossopharyngeal), X (vagus) and XI (spinal) deficit. This case exemplifies that knowledge of nervous anatomy and physiology is the basis of the semiology of the nervous system. PMID- 22670450 TI - [Just a wish for the nursing profession]. PMID- 22670451 TI - ["Our objective is to have the profession adopt the Order" (interview by Yasmina Ouharzoune, Sylvie Warnet)]. PMID- 22670452 TI - [The health professions, a future growth area]. PMID- 22670453 TI - [World tobacco free day]. PMID- 22670454 TI - [Diagnosis and treatments for patients suffering from bowel cancer]. AB - After lung cancer, bowel cancer is the second most deadly cancer in France. Since 2009, it has been subject to an organised screening programme aimed at reducing mortality rates. The nursing care brings together a multi-disciplinary team which, from the diagnosis announcement and throughout the treatment, seeks to place the patient at the centre of the therapeutic project. PMID- 22670455 TI - [Announcement of bad news and patient support]. AB - Being unprepared for the announcement of bad news can influence patients' perception of their illness and upset their psychological balance. While the announcement of the diagnosis, the prognosis and the treatment remains a medical act, the psychological preparation around this announcement is a nursing act which forms an integral part of the nursing role. PMID- 22670456 TI - [The role of the stoma therapy nurse in the preoperative period]. AB - Based on clinical reasoning and nursing expertise, stomatherapy care helps to improve the stoma patient's quality of life. In the preoperative period, the stoma therapist seeks to expand on the information provided by the surgeon, to establish a helping relationship while preparing already, the stoma patient's future autonomy. PMID- 22670457 TI - [Nursing care adapted to different types of stoma]. AB - As soon as the patient leaves the operating theatre, in the recovery room, then in the surgical clinical unit, nurses carry out stoma care and monitor the possible occurrence of complications. Stoma therapists educate patients in caring for the stoma themselves, advise them in the choice of equipment and support them as they regain autonomy. PMID- 22670458 TI - [The training of stomatherapy nurses]. AB - Advising and educating patients and resource people, providing information and training, leading a public-private-freelance and associative care network as well as being involved in a research process are essential elements of the practice of a stoma therapist. Although based on specific training this practice is not so much a speciality as a specificity. PMID- 22670459 TI - [Therapeutic education at the heart of the patient treatment pathway]. AB - The surgical treatment of bowel cancer often results in a digestive stoma, either temporary or permanent. Stoma patients must learn to live with this changed body and intestinal function. They must also adapt their lifestyle to these changes. It is in this direction which the stoma therapy nurse supports the patient. PMID- 22670460 TI - [The peer support role of patient experts]. AB - As a complement to the care provided by stomatherapy nurses, expert stoma patients lend an ear and provide precious peer support based on their own experience as a stoma patient. Trained in this particular approach, they adopt a course of action adapted to the needs of the patients visited during the perioperative period. PMID- 22670461 TI - [The nurse's paradox or the virtue of care cessation]. AB - Between treatment which brings no improvement or which can even result in dangerous side effects and the lethal risk of the disease itself, the nurse is often faced with delicate situations. They must examine their conscience and choose between ministering treatment at all costs and not applying a medical prescription. PMID- 22670462 TI - [Assessment of oedema]. AB - Oedema signals a more or less significant disturbance of the capillary balance. Generalised or localised, it usually affects the lower parts of the body, notably the lower limbs. It can be a sign of heart failure which is why it is important for nurses to know how to spot, classify and above all assess the different types of oedema. PMID- 22670463 TI - [An unexpected delivery in Mayotte]. AB - The particular social-cultural context of Mayotte is resulting in an increase in the number of unexpected home births. When a secondary emergency response vehicle is dispatched, A & E nurses are involved in providing prehospital care, sometimes in difficult conditions, as one nurse testifies in this account. PMID- 22670464 TI - [Reclaiming the body through touch-relaxation massage]. AB - More than just a simple technique, touch-relaxation massage in the protected haematology unit of Nantes general hospital has become a real personalised act of care, in what are often difficult conditions of hospitalisation. It forms part of the global support of patients suffering from leukaemia. PMID- 22670465 TI - [The nurse as the last line of defence against quality defects in medicines]. AB - The administration of medicines, the last stage in the process, is mainly carried out by the nurse. She is therefore the last person to be able to intercept any quality defects in the medication which, despite the stringent safety measures taken by pharmaceutical laboratories throughout their manufacturing processes, remain unavoidable. These interceptions are vital for the patient's safety. PMID- 22670466 TI - Discussing diets with patients. PMID- 22670467 TI - [The nurse managing a burn]. PMID- 22670468 TI - [Diogenes syndrome]. PMID- 22670469 TI - [Reinforcing self efficacy of students: a pedagogy of success]. PMID- 22670470 TI - [Radial artery puncture]. PMID- 22670471 TI - In silico analysis of peptide binding features of HLA-B*4006. AB - HLA-B*4006 is the most common allele amongst Indians. It belongs to the 'HLA-B44 supertype' family of alleles that constitute an important component of the peptide binding repertoire in populations world over. Its peptide binding characteristics remain poorly examined. The amino acid sequence and structural considerations suggest a small, poorly hydrophobic 'F' pocket for this allele that may adversely affect the interaction with the C terminal residue of the antigenic peptide. Contribution of auxiliary anchor residues (P3) of the peptide has also been indicated. To examine these aspects by in silico analysis, HLA B*4001, 4002, and 4006 alleles were modeled using HLA-B*4402 as a template. Eleven peptides, known to bind alleles of this family, were used for docking and molecular dynamics studies. Interaction between the amino group (main-chain) of P3 residue and Tyr99 of the alleles was seen in majority of peptide-complexes. Hydrophobic interactions between Tyr7 and Tyr159 with N terminal residues of the peptide were also seen in all the complexes. Replacement of Trp95 by leucine in HLA-B*4006 resulted in reduction of binding free energy in 8 out of 9 complexes. In summary, the analysis of the modeled structures and HLA-peptide complexes strongly supports the adverse effect of Trp95 at pocket F and the possible role of the third residue of the antigenic peptide as an auxiliary anchor in HLA B*4006 peptide complexes. In the light of suggested promiscuous peptide binding pattern and association with risk for tuberculosis/HIV for this allele, the ascertainment of the predicted effects of Trp95 and role of P3 residue as an auxiliary anchor by this preliminary in silico analysis thus helps define direction of the further studies. PMID- 22670473 TI - Cold stress interaction on organophosphate insecticide poisoning: age-related assessment in rat cerebral cortex. AB - The present study was undertaken to identify the nature of the interactive effects of chlorpyrifos (CPF) and cold stress (15 degrees and 20 degrees C) on the activities of acetyl cholinesterase (AChE), choline acetyl transferase (ChAT), Na+, K(+)-ATPase and malondialdehyde (MDA) level in the cerebral cortex of 1 week, 3 weeks and 3 months of age. The results indicated an interaction of CPF with age of animal and cold exposure resulting in marked decrease in the activity levels of AChE, ChAT, Na+, K(+)-ATPase, followed by increased MDA levels. Overall, the effects of co-exposure of cold stress and CPF were appreciably different from either of the exposures. However, synergistic-action of CPF and cold stress at 15 degrees C showed a greater inhibition of AChE, ChAT, and Na+, K(+)-ATPase in comparison with CPF or cold stress alone and together at 20 degrees C. The results reveal that young animals are markedly more sensitive to interactive effects of CPF and cold stress than adults. PMID- 22670472 TI - Effect of L-deprenyl treatment on electrical activity, Na+, K+ ATPase, and protein kinase C activities in hippocampal subfields (CA1 and CA3) of aged rat brain. AB - L-deprenyl is considered to protect against age-related cognitive deficits by improving long-term learning/memory in the aged brain. The CA1 and CA3 hippocampal areas are the sites at which initial learning and memory processes occur. Chronic deprenyl treatment significantly augmented the basal electrical firing rate (multiple-unit action potentials), and Na+, K(+)-ATPase and protein kinase C activities of both CA1 and CA3 indicating that the drug increased the excitability of CA1 and CA3. The increase, however, was much greater in CA1 than in CA3 suggesting that deprenyl can improve longer-term learning in aged animals by its excitability-enhancing action in CA1. The drug also countered the ageing related loss of hippocampal protein kinase C activity. PMID- 22670474 TI - Anti-apoptotic potential of gymnemic acid phospholipid complex pretreatment in Wistar rats with experimental cardiomyopathy. AB - Cardiomyocyte apoptosis in heart failure has been the topic of research in many recent studies. In the present investigation, the potential cardioprotective effect of gymnemic acid phospholipid complex (GPC) on myocardial apoptosis and cardiac function was studied in doxorubicin (DOX; 30 mg/kg/ip/single dose) induced cardiomyopathy model in rats. Doxorubicin induced cardiomyopathy was evidenced by significant hemodynamic changes (increased systolic, diastolic, mean arterial pressure and heart rate), decreased heart weight to body weight ratio, increase in serum lactate dehydrogenase (LDH) and Ca2+ levels and decrease in myocardial Na+/K+ ATPase levels along with caspase-3 activation. A marked reduction in glutathione, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, superoxide dismutase and catalase levels along with increase in the levels of thiobarbituric acids (TBARS) were also observed in rat myocardium. In addition, DNA laddering observed on agarose gel electrophoresis and cardiac histopathology study further supplemented myocardial apoptosis. Pre treatment with GPC significantly reduced DOX-induced cardiac toxicity, including improvement of hemodynamic variables and heart weight to body weight ratio, decreased serum Ca2+ level and LDH levels, myocardial caspase-3 levels, increased Na+/K+ ATPase levels and decreased myocardial TBARS levels and elevated antioxidant enzymes as compared to pathogenic control group. Further, the anti apoptotic effect of GPC was verified by prevention of internucleosomal DNA laddering on agarose gel electrophoresis and attenuation of histopathological perturbations by doxorubicin. These observations demonstrate that GPC might serve as a cardioprotective formulation in DOX-induced cardiomyopathy in rats. PMID- 22670475 TI - Curcumin increases vasodilatory effect of cilostazol in diabetic rat aorta. AB - Increased generation of oxidants and (or) reduced endogenous antioxidant defense mechanisms are associated with the etiology of diabetic vascular complications. The aim of the present study was to evaluate whether curcumin supplementation increases the vasodilatory effect of cilostazol in streptozotocin induced diabetic rat aorta. Cumulative addition of cilostazol caused concentration dependent relaxations of thoracic aorta rings. The sensitivity and the maximal response to cilostazol were significantly higher in control than those in diabetic animals. Treatment with curcumin in control rats increased the sensitivity to cilostazol. Further, in aortic rings from diabetic rats treated with curcumin, the responses to cilostazol were significantly increased in comparison to the response in aorta from untreated diabetic rats. It can be conclude, that curcumin increases the cilostazol-induced vasodilation in diabetic rat aorta. PMID- 22670476 TI - Progression of early phase diabetic nephropathy in streptozotocin-induced diabetic rats: evaluation of various kidney-related parameters. AB - Diabetic nephropathy (DN) is one of the serious secondary complications of diabetes, which results in end-stage renal failure. Reports on the progressive nature of early phase DN especially with respect to kidney parameters such as kidney weight, type IV collagen excretion, total kidney and urinary glycosaminoglycans (GAGs) are few. This work was undertaken to determine systematically the progression of early phase DN in relation to various kidney related parameters for a period of four months. Experimentally-induced diabetic rats were grouped based on fasting blood glucose levels. Various basic and kidney related parameters such as kidney weight, microalbuminuria, urinary excretion of GAGs and type IV collagen, total kidney GAGs, histopathology, glomerular area and glomerular volume were examined in control and diabetic rats. There was a progressive increase in fasting blood sugar, urine sugar, kidney weight, microalbuminuria, urine glycosaminoglycans, urine type IV collagen, glomerular area and glomerular volume but there was a progressive decrease in kidney glycosaminoglycans. Glomerular sclerotic condition was aggravated with the increase in duration of diabetes from 1 to 4 months. Onset of DN in rats begins subtly after one month of diabetes but gets vitiated and more pronounced at the end of four months. PMID- 22670477 TI - Protective effect of Tribulus terrestris linn on liver and kidney in cadmium intoxicated rats. AB - Administration of cadmium (Cd) significantly increased the peroxidation markers such as malondialdehyde and protein carbonyls along with significant decrease in antioxidant markers such as super oxide dismutase and reduced glutathione in liver and kidney tissues. Cadmium also caused a significant alteration in hepatic and renal functional markers in serum viz. total protein, albumin, alanine transaminase, blood urea nitrogen and creatinine. Prominent pathological changes observed in liver were severe vascular and sinusoidal congestion with diffuse degenerative changes and mononuclear infiltration into peripheral areas, while the kidney showed vascular and glomerular congestion, cloudy swelling of tubular epithelium. Coadministration of ethonolic extract of T. terrestris or vitamin E along with Cd significantly reversed the Cd induced changes along with significant reduction in Cd load. PMID- 22670478 TI - Developmental and neurobehavioural toxicity study of arsenic on rats following gestational exposure. AB - To characterize developmental and behavioral alterations induced by arsenic exposure, Albino rats were exposed to arsenic (0, 1.5, 3.0 and 4.5 mg/kg/day/po) from gestation day 8 to till parturition and the offspring were observed over the first 3 postnatal weeks, until they were weaned on post-natal day (PND) 21. Once the pups were delivered (PND0), the treatment was discontinued. All pups were assessed for physical development, reflex development, strength and motor coordination from standard neurobehavioural developmental test batteries beginning on PND1. Gestational administration of arsenic at tested dose levels, showed no significant changes in the day of appearance of eye opening, startle reflex, negative geotaxis and spontaneous alteration performance in comparison to the control group. The number of live fetuses, mean fetal body weight and percentages of resorptions or malformations per litter were not affected by arsenic exposure. No treatment-related malformations or developmental variations were noted at any exposure level, suggesting that arsenic exposure at this dose level did not adversely affect behavioural endpoints of developmental toxicity. PMID- 22670479 TI - Influence of mating histories and age on female remating behaviour in a few closely related species of Drosophila nasuta subgroup. AB - Female remating with more than one male leads to coexistence of sperm from different males in the same female, thus creating a selection pressure on sperm. To understand the extent of divergence in the reproductive behaviour among closely related species, in the present study, the influence of first mating histories like mating latency, duration of copulation and age of flies have been analysed on female remating behaviour in closely related Drosophila nasuta subgroup species with varying levels of reproductive isolation. The time taken for the once mated females to remate varied from 7 days in D. s. sulfurigaster to 19 days in D. s. neonasuta after first mating. The female remating frequency varied from a minimum of 29% in D. s. neonasuta to a maximum of 95% in D. s. sulfurigaster. The younger flies, which had remating latency of three times less than aged flies, show 100% remating frequency. In addition, it was observed that the duration of copulation in the first mating influences the remating behaviour among the nasuta subgroup members. The results revealed that D. nasuta subgroup members despite being closely related differ in their reproductive behaviour. PMID- 22670481 TI - Real-world research expands beyond comparing medications. PMID- 22670480 TI - Regeneration of plantlets from mature embryo calli of Western Ghats land race cultivar of rice, Oryza sativa L. AB - The Malnad region located in the Western Ghats of Karnataka is known for the cultivation of indigenous rain fed land race cultivar of rice. The present study was to investigate the callogenic and caulogenic potentialities of the two indigenous rice cultivar namely Karimundaga and Kanadatumba using dehusked mature embryo explants. For callus and shoot bud differentiation, the explants were cultured on Murashige and Skoog (MS) medium supplemented with 2,4-D (1-3 mg/L), IAA (1-2 mg/L), Kn (1-4 mg/L) and BAP (1-4 mg/L). The morphogenic potentialities of the two rice cultivar differed in texture of callus. In both the cultivar callogenic frequency was optimized at 1 mg/L 2,4-D concentration, it was 94% in Karimundaga and 58% in Kanadatumba. Supplementation of IAA either alone (1-2 mg/L) or in combination with Kn or BAP at 1 to 4 mg/L concentration of each induces shoot bud differentiation from the calli. In the cultivar Karimundaga caulogenic frequency was highest (10.60 +/- 2.55) at 1.0 mg/L IAA and 4.0 mg/L BAP concentration. While in the cultivar Kanadatumba highest number of shoot buds (7.90 +/- 2.69) was differentiated at 1.0 mg/L IAA and 4.0 mg/L Kn concentration. The calli derived regenerants were successfully acclimatized in the greenhouse and agro-morphological variations were evaluated. The growth characteristics and yield related parameters exhibited by in vitro plants were lower than the in vivo plants. PMID- 22670482 TI - 'Population-based,' meet 'patient-centered'. PMID- 22670483 TI - How to combat Pharma's costly coupon programs. PMID- 22670484 TI - 4 payer trends to control specialty pharmacy costs. PMID- 22670485 TI - 'New' health care organizations will truly manage care. PMID- 22670486 TI - Reviewing the evidence for using continuous subcutaneous metoclopramide and ondansetron to treat nausea & vomiting during pregnancy. AB - OBJECTIVE: To examine the medical evidence regarding the clinical efficacy and cost-effectiveness of the application of continuous subcutaneous metoclopramide and ondansetron to treat nausea and vomiting during pregnancy. STUDY DESIGN: All of the published peer-reviewed articles on the subject were assembled and assigned a level of evidence based on research design. The search uncovered one level II matched, controlled trial and three level III uncontrolled, retrospective case series published in peer review journals, as well as a book chapter. The book chapter, although not subjected to the peer-review process, is included in this review due to the paucity of other evidence. RESULTS: The matched cohort trial showed that continuous subcutaneous metoclopramide is significantly less-tolerated than continuous subcutaneous ondansetron (31.8% vs. 4.4%; P < 0.001). The four case series reported complete symptom resolution for 63.9% to 75% of the patients. Complications arose in 24.9% to 30.5% of the selected cases that were severe enough to require discontinuation of therapy. Complications included side effects of a worsening of symptoms. All of the trials are retrospective and observational in nature and, therefore, subject to the limitations inherent in the research design. Absent the benefit of meaningful cohort controls, comparative statements effectiveness cannot be substantiated with the available data. CONCLUSION: Randomized, controlled trials of sufficient power are necessary before long-term continuous subcutaneous metoclopramide or ondansetron can be used on a widespread basis to treat nausea and vomiting during pregnancy. Cost approximations in the case series are reported and, when compared to the cost of other methods of treatment previously published in the medical literature, the therapy appears to be cost-prohibitive. However, definitive statements cannot be made regarding cost-effectiveness until clinical efficacy is demonstrated through a sufficiently powered, well-designed, randomized control trial (RCT). Until such time, the therapy should remain experimental and coverage be restricted to intractable hyperemesis gravidarum (HG) that is unresponsive to more-conventional treatment options. PMID- 22670487 TI - Molina watches the kids while mom gets examined. PMID- 22670488 TI - Biomarker panel for colon cancer rivals fecal occult blood test. PMID- 22670490 TI - [The centenary of the Israel Medical Association]. AB - On January 12th 1912, six Jewish physicians and one pharmacist assembled in Tel Aviv to proclaim the founding of the Jaffa Hebrew Medical Society. One year later the Jewish doctors of Jerusalem established the "Society of Hebrew Speaking Physicians". On 28th December, 1918 a few weeks after the end of World War 1, both organizations merged into the Hebrew Medical Association which later became the Israel Medical Association (I.M.A.). The Association played a leading role in the advancement of medicine in the Holy Land and was instrumental in imposing the Hebrew medical terminology in the newly founded State of Israel. PMID- 22670489 TI - Births: final data for 2009. AB - OBJECTIVES: This report presents 2009 data on U.S. births according to a wide variety of characteristics. Data are presented for maternal characteristics including age, live-birth order, race and Hispanic origin, marital status, hypertension during pregnancy, attendant at birth, method of delivery, and infant characteristics (period of gestation, birthweight, and plurality). Birth and fertility rates by age, live-birth order, race and Hispanic origin, and marital status also are presented. Selected data by mother's state of residence are shown, as well as birth rates by age and race of father. Trends in fertility patterns and maternal and infant characteristics are described and interpreted. METHODS: Descriptive tabulations of data reported on the birth certificates of the 4.13 million births that occurred in 2009 are presented. Denominators for population-based rates are postcensal estimates derived from the U.S. 2000 census. RESULTS: The number of births declined to 4,130,665 in 2009, 3 percent less than in 2008. The general fertility rate declined 3 percent to 66.7 per 1,000 women aged 15-44 years. The teenage birth rate fell 6 percent to 39.1 per 1,000. Birth rates for women in each 5-year age group from 20 through 39 years declined, but the rate for women 40-44 years continued to rise. The total fertility rate (estimated number of births over a woman's lifetime) was down 4 percent to 2,007.0 per 1,000 women. The number and rate of births to unmarried women declined, whereas the percentage of nonmarital births increased slightly to 41.0. The cesarean delivery rate rose again, to 32.9 percent. The preterm birth rate declined to 12.18 percent; the low birthweight rate was stable at 8.16 percent. The twin birth rate increased to 33.2 per 1,000; the triplet and higher order multiple birth rate rose 4 percent to 153.5 per 100,000. PMID- 22670491 TI - [Silicone implants and breast cancer--is it so?]. PMID- 22670492 TI - [Autoimmune or autoinflammatory syndromes induced by adjuvants]. PMID- 22670493 TI - [Physicians' strikes--ethical considerations]. AB - Strikes in general represent a solution based on a form of coercion. Historically, the striker caused direct damage to his employer, who was responsible for the perceived unfair treatment of the employee. In the case of strikes in the public sector, the employer is generally not harmed, but innocent citizens suffer in order to pressure the government agencies, a questionable practice from an ethical viewpoint. Physicians' strikes have more serious ethical problems. They cause suffering and death to innocent citizens. They violate the ethical codes to which physicians have committed themselves as professionals, and they seriously impair the trust of the public in physicians. Better and more ethical ways to provide fair compensation for physicians must be employed, perhaps like those used for judges and members of the IDF. PMID- 22670494 TI - [Tay-Sachs disease in non-Jewish infant in Israel]. AB - Tay-Sachs disease, also known as GM2 gangliosidosis or Hexosaminidase A deficiency is an autosomal recessive genetic fatal disorder. The disease is known to appear in East European Ashkenazi Jews, North African Jews, and Quebec French Canadians exclusively, but, with different frequency and type of mutation. Its most common variant is the infantile type Tay-Sachs disease. Juvenile and late onset forms of the disease are infrequent and slowly progressive. At nearly 3 to 6 months old, a baby with Tay-Sachs progressively loses his motor skills and attentiveness. Startle responses and hyperreflexia become prominent, especially on eliciting deep patellar and Achilles reflexes, as a consequence of neurodegeneration of the upper motor neuron. Other systemic damage ensues gradually; seizures, blindness, spasticity of limbs, inability to swallow and breathe, and eventually the baby dies at 1-4 years of age. All Tay-Sachs patients have a "cherry red spot", easily seen in the macula area of the retina, using an ophthalmoscope. The "cherry red spot" is the only normal part of the retina in these sick babies. The case presented here emphasizes that Tay-Sachs disease is sometimes misdiagnosed at first visits even by an experienced clinician, because of his lack of awareness that this disease is not exclusively a Jewish disease. PMID- 22670496 TI - [Brain natriuretic peptide (BNP) level predicts long term ventricular arrhythmias in patients with moderate to severe left ventricular dysfunction]. AB - BACKGROUND: Brain natriuretic peptide (BNP) is a powerful predictor of mortality in patients with left ventricular dysfunction. Since malignant ventricular arrhythmias such as sustained ventricular tachycardia (VT) and ventricular fibrillation (VF) are a major cause of death among those patients, we postulated that BNP levels can predict their long-term occurrence. OBJECTIVES: To study the association between malignant ventricular arrhythmias and BNP level over a long term follow-up. METHODS: We prospectively followed 94 patients with ischemic heart disease and left ventricular dysfunction, all implanted with an implantable cardioverter defibrillator (ICD). BNP level was measured at baseline and ICD interrogation and clinical status were recorded at 6 months intervals for a median of 3.5 years. RESULTS: Patients with BNP levels in the highest quartile experienced significantly more arrhythmic events than those at the lower three quartiles (OR 2.2, 95% C.I 1.2-4.2). In a multivariate analysis only BNP level predicted arrhythmic events. Among patients implanted for primary prevention of sudden cardiac death, BNP at the lowest quartile significantly predicted low event rate. CONCLUSION: While high BNP level is predictive of malignant ventricular arrhythmias, low levels among patients implanted for primary prevention can identify a low risk subgroup for which the ICD might be of borderline therapeutic benefit. PMID- 22670495 TI - [Alertness is its own reward: adult type Hirschprung's disease--clinical description of first two cases in Israel]. AB - Hirschprung disease is well known. The basic pathogenesis is lack of parasympathetic ganglia in the large bowel wall, part of it, or all of it. The absence of these ganglia paralyzes the involved segment leading to obstruction. Almost all babies are diagnosed and operated upon in their first year. Few rare cases manage to grow and reach maturity without diagnosis. These patients are characterized by severe constipation and grade III-IV hemorrhoids. This is adult type Hirschprung's disease. Two first cases in Israel were diagnosed, patients were operated upon, and recovered. Adult type Hirschprung's disease is reviewed and various surgical options are discussed. PMID- 22670497 TI - [Hearing loss due to chemotherapy and radiation therapy in young children]. AB - INTRODUCTION: Modern treatment of pediatric cancer patients has improved survival and life expectancy. However, treatment is associated with significant side effects, including hearing loss. Hearing impairment has an important impact on language, communication and social skills, as well as on academic performance in school. AIMS: 1. Characterize hearing loss caused by treatment of pediatric cancer. 2. Define the impact of hearing loss on language development. 3. Describe techniques for intervention. MATERIAL AND METHODS: A retrospective review of ten children averaging five years of age who were referred to MICHA, a center specializing in treating hearing impaired children. For each child, at least four hearing tests were obtained, various language acquisition tests administered and methods of interventions recorded. RESULTS: All the subjects had high-tone symmetric sensorineural hearing loss; at 4000 Hz it reached 80 dB HL. Low frequency tones were better preserved. Pure-tone thresholds were worse than speech reception thresholds. Hearing aids improved hearing thresholds. Nine out of the ten children experienced a delay in language acquisition. The treatment plan included: hearing aids, hearing training, intervention in language and communication skills, emotional support and preparation for elementary school. CONCLUSIONS: Hearing loss amongst pediatric cancer patients as a consequence of treatment is extremely common. Delays in acquisition of language skills are seen in the majority of these children. DISCUSSION AND SUMMARY: Pediatric cancer patients should be referred to a proper diagnostic and intervention program. They are likely to benefit from monitoring the hearing before, during and after treatment, and from interventions to improve their hearing, language and communication skills. In addition, audiometry and otoacoustic emissions should be used to identify early damage to the inner ear. Noise and further exposure to ototoxic medications should be avoided. PMID- 22670498 TI - [The effect of platelet transfusion on traumatic intracranial hemorrhage among patients treated with aspirin]. AB - BACKGROUND: Head trauma represents a serious medical and socio-economical problem owing to its related morbidity and mortality. One of its serious complications is traumatic intracranial hemorrhage (TICH). There is evidence that TICH has a tendency to expand, especially during the first hours following injury. Aspirin has a central role in preventing thromboembolic complications in atherosclerotic conditions. This effect is mediated through the inhibition of platelet activity. There is a theoretical concern that treatment prior to the head injury with aspirin may expand the size of TICH. The purpose of the current study was to evaluate the effect of platelet transfusion on the extent of TICH expansion among patients treated with aspirin. METHODS: This retrospective study includes patients admitted to the Tel-Aviv Medical Center and the Tel-Hashomer Medical Center between 1/12/2004 and 31/10/2008. Patients were included if they underwent closed head injury, were treated regularly with aspirin prior to the injury, and had radiological evidence of an intraparenchymal hemorrhage or contusion (IPHC) or an acute subdural hematoma (ASDH]. The interval between the injury and the first computed tomography [CT] scan was not longer than 12 hours, and the interval between the first CT scan and the control CT scan was not longer than 24 hours. The effect of platelet transfusion administered between these two CT scans on the radiological and clinical outcomes was evaluated by a comparison between a group of patients treated with platelet transfusion (group A) and a group of patients who weren't treated with it (group B). RESULTS: A total of 44 patients were included in the study: 14 patients had IPHC, 40 had ASDH and 10 had both IPHC and ASDH. In the IPHC group the frequency of hemorrhagic expansion and the extent of expansion were greater in group A than in group B. Possibly, an earlier first CT, longer duration between both CT scans and a larger hemorrhage volume on CT1 in group A may explain these differences. In the ASDH group the frequency of hemorrhagic expansion was lower in group A than in group B, but without statistical significance. There was no significant difference in the extent of hemorrhagic expansion between the two treatment groups. CONCLUSIONS: From this study it appears that platelet transfusion within 36 hours post injury for patients with TICH who were treated with aspirin prior to the head injury does not reduce the rate or extent of hemorrhagic expansion. However, owing to the limitations of the present study, this conclusion should be considered with caution. We recommend evaluating this issue in a prospective, randomized, multi center study. PMID- 22670499 TI - [Adjuvant treatment with trastuzumab in early breast cancer]. AB - The introduction of new biological agents into the clinic has had a major impact on breast cancer care. Of all well-studied biological agents, Trastuzumab is the only one that has become part of the standard therapy for advanced as well as for early breast cancer. Dr. Tahover and her colleagues' review in this issue of "Harefuah" presents the pivotal trials that have brought a change of practice in the adjuvant treatment of patients with breast cancer and HER2 positive tumors. More than 10,000 patients with tumors that were defined as human epidermal growth factor receptor 2, ErbB-2 positive have been recruited into these trials. Trastuzumab was given concomitantly with or sequentially after chemotherapy. The review teaches us that despite this large cohort, several crucial issues need further clarification: Exactly who are the candidates for this specific treatment? What is the preferred protocol for the combination of Trastuzumab and chemotherapy? What is the optimal duration of treatment with Trastuzumab in the adjuvant setting? In this editorial we discuss these topics based on published data from prospective and retrospective studies. PMID- 22670500 TI - [Update: adjuvant trastuzumab in HER2 positive breast cancer]. AB - Some of the women who undergo surgery for the removal of breast cancer will need adjuvant treatment with chemotherapy, hormonal therapy, biological therapy or radiation therapy. In patients whose tumor expresses HER2, the adjuvant treatment will include Trastuzumab. In a number of prospective randomized trials performed in recent years, Trastuzumab was proven to have a significant effect in reducing by half the incidence of the recurrence of the disease and reducing the risk of death by a third. It is important to provide Trastuzumab as early as possible, together with the chemotherapy, unless treatment with doxorubicin is needed and then Trastuzumab is given later. The most significant side effect of Trastuzumab is cardiac toxicity, which is manifested in most cases by an asymptomatic decrease of the left ventricular ejection fraction in 2.3-17.3% of patients, although in most cases this has no clinical significance. Symptomatic heart failure is a rare event in Trastuzumab treated patients, occurring in 0-4% of patients and it is generally reversible with Trastuzumab discontinuation. In this review we summarize the current perspective on Trastuzumab and discuss adjuvant treatments in HER2-positive early breast cancer. PMID- 22670501 TI - [Compliance with diagnostic MRI in the workup of sudden sensorineural hearing loss]. AB - INTRODUCTION: Sudden sensorineural hearing loss (SSNHL] can be the presenting symptom of an acoustic neurinoma. High sensitivity and specificity rates define magnetic resonance imaging (MRI) of the brain and internal acoustic canal as the gold standard for the diagnosis of retro-cochlear pathologies. A previous study revealed low compliance rates (49%] for performing an MRI after an episode of SSNHL; 15% of patients who had an MRI were diagnosed with a retro-cochlear pathology. AIM OF STUDY: To evaluate current compliance rates for performing an MRI of the brain and internal acoustic canal after an episode of SSNHL. MATERIAL AND METHODS: The study cohort included 41 patients, 24 females and 17 male, with an average age of 49.8 +/- 16.8 years (range, 16-78 years), who were diagnosed with SSNHL and admitted for treatment between December 2009 and June 2010. RESULTS: Two months after discharge from hospitalization, only 29 patients (70.7%) returned for the scheduled followup. Only 21 patients (51.2% of those admitted) had an MRI of the brain and internal acoustic canal, as was recommended upon their discharge. Three of those who had an MRI were diagnosed with a retro cochlear pathology. In 20 patients [48.8%) who did not perform an MRI, a retro cochlear pathology could not be ruled out. CONCLUSIONS: Compliance rates for performing an MRI after an episode of SSNHL haven't changed in recent years. The main reason seems to be poor patients' compliance, as well as their general practitioners and health insurance companies. Ruling out retro-cochlear pathologies by means of MRI is highly important and considered common medical practice. Guidelines regarding the importance of MRI after an episode of SSNHL should be updated and reinforced. PMID- 22670502 TI - [Cancer survivorship: an evolving medical field]. AB - More than a quarter of a million IsraeLi citizens live today with the diagnosis of cancer being a part of their past medical history. The volume of this population is going to enlarge in coming years. These patients tend to suffer from several unique medical and psychosocial difficulties due to their original malignant disease and its risk factors, as a consequence of the antineoplastic treatments they had received, and as a result of exceptional presentation of concomitant non-neoplastic diseases. In this review, we describe the current dilemmas that exist in the medical community concerning the appropriate setting and extent of care that are needed in order to deliver suitable care for this growing population, and emphasize the need for further research and the development of clinical excellence in the treatment of this population. PMID- 22670503 TI - [Dr. Moshe Sherman--the first otolaryngologist in Eretz-Israel: 100 years since his arrival]. AB - On 4.8.1911 Dr. Moshe Sherman landed at the port of Jaffa. He was the first otolaryngologist in Eretz-Israel and for one year he was the only specialist in the country. Dr. Sherman was born in Nikolayev (Russia) in 1881. He started his medical education in Odessa, continued in Berlin, graduated in 1907 at the University of Dorpat (Estonia) and pursued postgraduate studies in otolaryngology at Moscow University. He settled in Jaffa, started a private practice and soon became a famous specialist. He volunteered at the Jewish hospital in Jaffa- "Shaar Zion", and twice a year spent several weeks in Jerusalem seeing patients and performing small operations. On January 1912 Dr. Sherman, together with another 5 physicians, laid the foundations for the first doctors' organization in Israel: "The Medical Society of Jaffa and Jaffa district". In 1918 Dr. Sherman was elected consultant at the Hadassah Hospital in Tel Aviv, and in 1932 a department for ear, nose and throat diseases was established there under his management. He was the founder and first chairman of the Ototaryngology Society in Eretz-Israel, and in 1935 was elected the chairman of the Jewish Medical Association in Eretz-Israel (later--its honorary president). He was the initiator and founder of the "World Fellowship", and the Editor in Chief of 'Harefuah' and "Michtav Lachaver". Dr. Sherman was the author of numerous papers related to his specialty and to the history of Jewish organizations in Eretz-Israel and, later, in the State of Israel. Dr. Sherman died in Tel Aviv on July 17th 1969. PMID- 22670504 TI - Challenges in diagnosis and treatment of latent tuberculosis infection. PMID- 22670505 TI - In-hospital mortality of intermittent vs daily antitubercular regimen in patients with meningeal tuberculosis--a retrospective study. AB - INTRODUCTION: The Revised National Tuberculosis Control Programme (RNTCP), the State-run Tuberculosis Control Initiative of the Government of India, recommends intermittent thrice a week Directly Observed Treatment Short course (DOTS) both during intensive phase and continuation phase for a total of nine months for tubercular meningitis. However, most recent guidelines recommend daily regimen. OBJECTIVE: Assessment of the in-hospital mortality in patients with meningeal tuberculosis. MATERIAL AND METHODS: We retrospectively analyzed the data of patients (n = 98) admitted with a diagnosis of meningeal tuberculosis from January 1st 2006 to December 31st 2009 in a tertiary care centre in South India. Thwaites index score of four or less was used for diagnosis of meningeal tuberculosis which is a weighted diagnostic index score for dichotomised clinical variables including age, blood white cell count, duration of illness, CSF total white cell count, and CSF neutrophil percentage. We compared in-hospital treatment outcome of patients on thrice weekly intermittent DOTS regimen with daily regimen patients. RESULTS: The inhospital mortality was same (27%) in the two treatment regimens (p 0.944). However, there was less incidence of hepatic dysfunction in the intermittent DOTS regimen, even though it was not statistically significant (p 0.148). CONCLUSIONS: In the short-term, both regimens have similar mortality outcomes and no statistically significant difference in hepatic dysfunction during the hospital stay. PMID- 22670506 TI - Impact of the RNTCPIRL-EQA-OSE visits on quality of sputum smear microscopy services of Gujarat, India. AB - OBJECTIVE: On-site evaluation of laboratories with standard checklist is a first step to promote effective and consistent supervision. The present study was carried out to evaluate the impact of the RNTCP- Intermediate Reference Laboratory External Quality Assessment- On-Site Evaluation visits on quality of sputum smear microscopy services of Gujarat, India. Data of three IRL-EQA-OSE visit rounds, carried out between January 2005 and December 2010 are presented here. MATERIAL AND METHODS: Within the Revised National Tuberculosis Control Programme EQA framework, the IRL, Ahmedabad visited all Gujarat District Tuberculosis Centres, and evaluated their sputum smear microscopy services. The study covered a cohort of 29 DTCs during each of the three IRL-EQA-OSE visits. The authors focused on section III of Annexure A to study and analyse the said impact. In order to convert qualitative data into quantitative one, the authors denoted a score of 1 to "Acceptable" (No Error) remark and 0 to "Not-Acceptable" (Error) one. RESULTS: A larger degree of improvement was noted in Standard Operating Procedure practices, Disinfection practices, and Internal Quality Control practices. Many DTCs did not retrain their laboratory staff in EQA methodology. The Gujarat DTCs achieved an overall score of (820/957) 86% during the initial OSE visits which consistently improved to (842/957) 88% and (885/957) 92% during the two follow-up OSE visits along with sustenance and improvement in many important laboratory parameters. CONCLUSION: The co-sponsoring organisation (IRL) recognises the challenges and therefore, is committed to supporting state level implementation of EQA through additional training, technical assistance to districts, and improving this technical guidance. By periodic IRL-EQA-OSE visits, sputum smear microscopy services can be sustained and improved at field level. PMID- 22670507 TI - An epidemiological study of multi drug resistant tuberculosis cases registered under Revised National Tuberculosis Control Programme of Ahmedabad City. AB - BACKGROUND: The emergence of resistance to anti-tuberculosis drugs in general and Multi Drug Resistan Tuberculosis (MDR-TB) in particular, has become a significant public health problem and an obstacle to effective TB control. Baseline and adequate information on epidemiological factors and their interaction are prerequisites for its effective control. OBJECTIVES: To study socio-demographic profile, housing environment, health-seeking behaviour, present and past history regarding treatment of tuberculosis, drug resistance pattern and the preventive practice adopted by the patients. METHODOLOGY: A cross-sectional study was carried out on 81 MDR-TB patients registered under RNTCP of Ahmedabad city during July 2007-June 2008. To accomplish the objectives, information was collected by personal interviews using pre-designed, pre-tested proforma. Data, so collected, was analyzed and tabulated using appropriate statistical software. RESULTS: More than 2/3rd were males and majority were in age group 16-45 years, educated up to primary level, living in overcrowded and ill-ventilated houses. Initially almost all had pulmonary TB. At the start of category II, maximum number of patients were defaulters, the prime cause being financial crunch. The mean number of Anti Tubercular Treatment (ATT) taken before start of category IV was 2.85. More than 90% experienced side-effects of drugs. Although indiscriminate spitting was less, other methods of sputum disposal were also unsafe. Resistance to all four drugs (H, R, S & E) was found in more than 2/3rd of cases. Smear and culture conversion rate at three month follow up was 62.0% and 58.7% respectively. Only one patient (1.2%) was reactive for HIV in the study. Most of the patients perceived some degree of improvement in their condition following treatment. CONCLUSION: Most of the MDR cases were living in poor environmental conditions, had previous history of TB and defaulter of treatment regimen prescribed. Motivation of private practitioners for increasing referrals, use of incentives and enablers, enhancing contact tracing and increasing awareness regarding sputum disposal practices and measures to prevent the spread are necessary for effective control of tuberculosis. PMID- 22670508 TI - Morphological anatomy of accessory fissures in lungs. AB - BACKGROUND: Knowledge of the position and grade of accessory fissures and lobes is necessary for appreciation of lobar anatomy and thus locating bronchopulmonary segments. METHODS: Morphological variations of accessory fissures and lobes of the lungs were studied in 40 pairs of lungs from cadavers. RESULTS: Four left sided lungs and two right-sided lungs showed accessory fissure in the lower lobe. Only one accessory fissure of left lung belongs to grade-ii and the remaining belongs to grade iii. [According to Craig and Walker's fissural classification] CONCLUSIONS: Awareness regarding accessory fissures and lobes is essential for performing lobectomies, segmental resection, for differential diagnosis and interpreting radiological images. PMID- 22670509 TI - Port site tuberculosis: a case report and review of literature. AB - A rare case of port site tubercular infection is reported. A young male patient presented, one month after laparoscopic inguinal hernia repair with discharging sinuses at the port sites. Biopsy of the sinus tract showed features of tuberculosis. Excision of sinus tract was done and the patient was started on anti-tubercular therapy, sinuses healed. Probably, the source of tubercular infection was laparoscopic instruments. Proper sterilization of laparoscopic instruments is necessary. PMID- 22670510 TI - Primary tubercular osteomyelitis of mandible: rare presentation of a common disease. AB - Secondary tuberculosis of mandible is an uncommon complication of primary tuberculosis elsewhere in the body, most frequently, in the lungs. Primary tuberculosis of the mandible is a very rare entity, of which only eight cases have been reported in literature till date. A case of primary tuberculosis of mandible in a 9-year-old girl is presented here. PMID- 22670511 TI - Lingual tuberculosis. AB - Oral tuberculosis is very rare and when present they are usually secondary to pulmonary tuberculosis. Tuberculous lesions of the tongue have become so infrequent that they are virtually a forgotten disease entity and may pose a diagnostic problem. The case reported in this paper emphasizes the importance of including tuberculosis in the differential diagnosis of any chronic oral ulcer. The low number of oral infections by M. tuberculosis could be due to underreporting. PMID- 22670512 TI - Status report on RNTCP. PMID- 22670513 TI - Mycobacterium tuberculosis triggers autoimmunity? AB - Mycobacterial infections are known to induce the development of autoantibodies. This study was therefore carried out in endemic areas to look for the prevalence of autoantibodies in pulmonary and extra pulmonary tuberculosis, with and without rheumatological symptoms suggesting a possible role of mycobacterial infection triggering autoimmunity. The results reveal that there is a need for further studies to be carried out in relation to possible autoimmune phenomenon linked with Mycobacterium tuberculosis infections. Tuberculosis patients should ideally be screened for the presence of various autoantibodies, particularly for a detailed study on anti-nuclear antibody (ANA) specificities. Their significance has to be deciphered to understand the role of these background autoantibodies produced. It is important to screen all tuberculosis patients for autoantibody profile and should be followed up after the treatment for any flaring up of autoimmune related symptoms. PMID- 22670514 TI - Tuberculous epididymitis-cytology-based diagnosis. PMID- 22670515 TI - [CRISPR adaptive immunity systems of procaryotes]. AB - CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a newly identified prokaryotic immunity system against foreign genetic elements. In contrast to other cellular defense mechanisms (e.g. restriction-modification) CRISPR-mediated immunity is adaptive and can be programmed to protect cells against a particular bacteriophage or conjugative plasmid. In this review we describe general principles of CRISPR systems action and summarize known details of CRISPR systems from different microorganisms. PMID- 22670516 TI - [Multilocus epimutations of imprintome in the pathology of embryo development]. AB - Genomic imprinting is one of the most significant epigenetic phenomena, which is involved in the support of eutherians and human embryo development. Molecular mechanisms of imprinting disturbance in the pathology of pre- and postnatal ontogeny are related to a considerable degree to aberrant DNA methylation of imprinted genes. At present time data about multiple abnormalities of DNA methylation arising simultaneously in several imprinted loci are accumulated. This fact brings up the problem of interpretation of imprintome structural and functional organization, as well as interaction of imprinted genes. At present study DNA methylation analysis of 51 imprinted genes in placental tissues of human spontaneous abortions was performed. The presence of several epimutations affected from four to 12 imprinted genes was observed in each embryo. Majority of epimutations (78%) had a postzygotic origin. It was shown for the first time that the total incidence of abnormal DNA methylation of maternal and paternal alleles of imprinted genes, which lead to suppression of embryo development, is significantly higher than the incidence of epimutations, which can lead to stimulation of ontogenesis processes. This fact supports at the epigenetic level the "sex conflict" hypothesis, which explains the appearance of monoallelic imprinted genes expression in the evolution of mammals. PMID- 22670517 TI - [Association study of renin-angiotensin system genes and hemostasis system genes with ischemic stroke among Russians of Central Russia]. AB - The analysis of alleles and genotypes frequencies of 14 SNP in genes of rennin angiotensin system (REN, AGT, AGTR1, AGTR2, BKR2, ADRB2) and hemostasis system (FGB, F2, F5, F7, ITGB3, SERPINE1, MTHFR), as well as ACE insertion-deletion polymorphism in patients with stroke comparing to healthy controls matched by age, sex and ethnicity has been carried out. The genotyping procedure included the amplification of selected gene sequences following by hybridization of fluorescently labeled fragments with SNP-specific DNA probes. The analysis of allele frequencies of each gene separately revealed no statistically significant differences between groups of patients with stroke and healthy donors. Also the complex study has been performed to estimate the contribution of rennin angiotensin system and hemostasis system genes to the genetic susceptibility to ischemic stroke among Russians from Central Russia using method MDR (Multifactor Dimensionality Reduction). The combination with increased risk for development of ischemic stroke was presented by complex genotype FGB G/- x ACE I/- x MTHFR C/- x SERPINE1 5G/5G (p = 0.03, OR = 2.4, 95% CI 1.1-5.3), which frequency was statistically significant higher in patients with stroke compared to healthy control. PMID- 22670518 TI - The complete mitochondrial genome of silver croaker Argyrosomus argentatus (Perciforems; Sciaenidae): genome characterization and phylogenetic consideration. AB - The complete mitochondrial genome sequence of the silver croaker, Argyrosomus argentatus, was obtained by using LA-PCR and sequencing. The mitogenome is 16485 bp in length, consists of 13 protein-coding genes, two ribosomal RNAs, 22 transfer RNAs, and a non-coding control region like those found in other vertebrates, with the gene order similar to that of typical teleosts. Most of the genes of A. argentatus were encoded on the H-strand, while the ND6 and eight tRNA (Gln, Ala, Asn, Cys, Tyr, Ser (UCN), Glu and Pro)) genes were encoded on the L strand. The reading frames of two pairs of genes overlapped: ATPase8 and 6 and ND4L and ND4 by ten and seven nucleotides, respectively. The origin of L-strand replication in A. argentatus was in a cluster of five tRNA genes (WANCY) and was 46 nucleotides in length. The conserved motif (5'-GCGGG-3') was found at the base of the stem within the tRNA(Cys) gene. Within the control region, we identified all of the conserved motifs except for CSB-F. PMID- 22670519 TI - [Association of chromosome 8q24 variants with prostate cancer risk in the Siberian region of Russia and meta-analysis]. AB - Compelling evidence demonstrates chromosome 8q24 as a prostate cancer susceptibility locus. In present work we studied whether the common variants of 8q24 region, rs6983267 and rs1447295, were associated with the sporadic prostate cancer risk in the Russian population. Polymorphisms were genotyped in 393 case and 384 control Russian Caucasian men from Siberia region. The A allele of rs1447295 was significantly associated with the risk of prostate cancer (OR[CI 95%] = 1.74 [1.26-2.4], p = 7.8 x 10(-4)). A common G-A haplotype for rs6983267 - rs1447295 also showed an association with prostate cancer risk in Russian population (OR[CI 95%] = 2.03 [1.1 - 3.75], p = 0.02). We performed a meta analysis combining our results with previous studies to evaluate the association between studied SNPs and prostate cancer risk. Meta-analysis has strongly supported the association for these SNPs (p < 10(-6)). Accordingly our study confirms the association between chromosome 8q24 and prostate cancer risk. PMID- 22670520 TI - [Study of the positional relationship of nucleolar chromatin and nucleolar compartments in somatic nuclei OPF the ciliate Didinium nasutum]. AB - We showed earlier that nucleoli in interphase ciliates Didinium nasutum, appearing on single ultrathin sections as individual structures, actually are parts of more complex network-like structures in which fibrillar component is located on periphery, and granular--in the central part of a nucleolus. It is known, that nucleolar organizers in D. nasutum are represented by chromatin bodies connected with nucleoli. In this work we used 3D reconstruction on the basis of serial ultrathin sections to study localization of chromatin bodies which by morphological criteria might correspond to nucleolar organizers. Our data showed, that all such chromatin bodies settled down outside of nucleoli, near the periphery of fibrillar component. Even those chromatin bodies which on single sections looked completely surrounded by fibrillar nucleolar component, actually settled down in fibrillar component cavities open to nucleoplasm. Analysis of distribution of nucleolar chromatin bodies allowed us to conclude that activity in different parts of interphase complex network-like nucleoli of D. nasutum is approximately the same. PMID- 22670521 TI - Expression and characterization of Escherichia coli derived hepatitis C virus ARFP/F protein. AB - Genome of the hepatitis C virus (HCV) contains a long open reading frame encoding a polyprotein that is cleaved into 10 proteins. Recently, a novel, so called "ARFP/F", or "core+1", protein, which is expressed through a ribosomal frame shift within the capsid-coding sequence, has been described. Herein, to produce and characterize a recombinant form of this protein, the DNA sequence corresponding to the ARFP/F protein (amino acid 11-161) was amplified using a frame-shifted forward primer exploiting the capsid sequence of the 1b-subtype as a template. The amplicon was cloned into the pET-24a vector and expressed in different Escherichia coli strains. The expressed protein (mostly as insoluble inclusion bodies) was purified under denaturing conditions on a nickel nitrilotriacetic acid (Ni-NTA) affinity column in a single step with a yield of 5 mg/L of culture media. After refolding steps, characterization of expressed ARFP/F was performed by SDS-PAGE and Western blot assay using specific antibodies. Antigenic properties of the protein were verified by ELISA using HCV infected human sera and by its ability for a strong and specific interaction with sera of mice immunized with the peptide encoding a dominant ARFP/F B-cell epitope. The antigenicity plot revealed 3 major antigenic domains in the first half of the ARFP/F sequence. Immunization of BALB/c mice with the ARFP/F protein elicited high titers of IgG indicating the relevance of produced protein for induction of a humoral response. In conclusion, possibility of ARFP/F expression with a high yield and immunogenic potency of this protein in a mouse model have been demonstrated. PMID- 22670522 TI - [Alterations of expression level of RASSFIA gene in primary epithelial tumors of various locations]. AB - Tumor-suppressor activity was established for RASSF1A gene by in vitro and in vivo including studies of knock-out mutated mice cells. Data on methylation of promoter region and expression decrease revealed mainly in cancer cell lines were reported. Here, analysis of RASSF1A mRNA quantity was performed for the first time in primary epithelial malignant tumors of five various locations from 130 patients by semi-quantitative RT-PCR. Representative sets of kidney, lung and breast carcinomas samples were studied. Preliminary data for RASSF1A expression in ovarian and colorectal carcinomas are also reported. Our system studies showed unexpected expression profiles, namely mRNA level increase more frequently (2-7 times) than decrease in renal, breast, ovarian, and colorectal carcinomas. Increasing RASSF1A mRNA level was revealed significantly more frequently in renal cell carcinoma (24/38, 63% vs. 8/38, 21%, P = 0.0004, by Fisher exact test) and ovarian carcinomas (8/13, 62% vs. 2/13, 15%, P = 0.0114). Only in non-small cell lung cancer decreasing and increasing of RASSF1A expression were observed with equal frequency (16/38, 42%). Noteworthy, for early clinical stages prevalence of increasing expression both in squamous cell lung cancer and in adenocarcinoma was revealed, and for advanced clinical stages evident prevalence of decreasing RASSF1A expression was established. Cases with increasing expression both in early and advanced stages of clear cell renal cell carcinoma were in prevalence, in advanced stages it was proved significantly (P = 0.0094). These data suggested that RASSF1A expression alterations were tumor specific. Mentioned above regularity could point onto ambivalent RASSF1A functions in tumors--a tumor suppressor gene and a proto-oncogene as well. PMID- 22670523 TI - [Comparative analysis of antirestriction activity of R64 ArdA and ArdB proteins]. AB - Antirestriction proteins ArdA and ArdB are specific inhibitors of the type I restriction-modification enzymes. The transmissible plasmid R64 ardA and yfeB (ardB) genes were cloned in pUC18 and pZE21 vectors. It was shown that the R64 ArdA and ArdB proteins inhibit only restriction activity of the type I restriction-modification enzyme (EcoKI) in Escherichia coli K12 cells. The dependence of the effectiveness of the antirestriction activity of the ArdA and ArdB proteins on the intracellular concentration was determined. Antirestriction activity of ArdB is independent from the ClpXP protease. Transcription of yfeB (ardB) gene in R64 plasmid is realized from the yfeA promoter. PMID- 22670524 TI - [The search of partners of a new mammalian selenium-containing protein V (SelV) and expression it's mRNA during ontogenesis and spermatogenesis]. AB - Selenium is a biologically active trace elements, which is part of several proteins, and thus linked with the activity of many organs, tissues and systems of organism. There are 25 mammalian selenoproteins at present, one of which is SelV (Selenoprotein V). Since this protein has thioredoxin-like folding and a conserved motif (CXXU, where C is cysteine, U-selenocysteine) in its catalytic center, it belongs to the family of redox proteins, whose members are involved in redox reactions. In this paper, we show that the redox protein SelV can interact with O-linked N-acetylglucosamine transferase (OGT) and proteins belonging to the family of ASB: Asb-17, and Asb-9. The specificity of interactions SelV with OGT and Asb-9, but not with Asb-17 is confirmed by coimmunopretsipitation. In addition, expression of SelV mRNA in the later stages spermatogenesis, as well as in puberty and reproductive periods of rats is shown. PMID- 22670525 TI - [The influence of UPF genes on the severity of SUP45 mutations]. AB - Eukaryotic cells possess special mechanism of the degradation of mRNAs containing premature termination codons (PTCs)--nonsense-mediated mRNA decay (NMD) pathway. In yeast Saccharomyces cerevisiae, the activity of this pathway depends on the recognition of the PTC by the translational machinery and interaction of translation termination factors eRF1 and eRF3 with Upf1, Upf2 and Upf3 proteins. Previously we have shown that decreasing of eRF1 amount causes an impairment of NMD. Here we show that deletion of either UPF1 or UPF2 increased viability of sup45 mutants, while effect of UPF3 deletion is allele-specific. Two-hybrid data have shown that aa 1-555 of eRF1 participate in interaction with Upf1. Deletion of each UPF gene leads to allosuppresson of ade1-14 mutation without changing eRF1 amount. Depletion of Upf1 does not influence synthetic lethality of sup45 and prion [PSI+]. It is possible that the absence of Upf1 (or its activator Upf2) leads to more effective formation of the translation termination complex and, consequently, increased viability of cells containing mutant termination factors. PMID- 22670526 TI - [Effect of nucleocapsid on multimerization of gypsy structural protein Gag]. AB - The structural protein (Gag) of the gypsy Drosophila retrovirus lacks matrix, but contains capsid and nucleocapsid domains. The Gag forms virus-like particles in a bacterial cell; besides, its capsid alone is able to form aggregates. However, aggregates assembled from the capsid were variable in size and displayed much less organization than particles formed by the whole Gag. The nucleocapsid exerts influence on the organization and structure of particles, and this function is directed by sequence of amino acid residues at its N-terminus (a nucleocapsid proximal part). The particle assembling occurs in the presence of any RNAs or single stranded DNA oligonucleotides. PMID- 22670527 TI - [Biosynthesis and purification of human beta2-adrenergic receptor expressed in methylotrophic yeast Pichia pastoris]. AB - Human beta2-adrenergic receptor is one of the most studied G-protein-coupled receptors. It plays a key role in autonomic nervous system and is a drug target in cardiovascular and pulmonary diseases. Despite the fact that its crystal structure was revealed, a physiological role and molecular mechanisms of its action remain largely unknown. We designed the construct pVR2ADRH, which contained the gene for human beta2-adrenergic receptor with a polyhistidine tag C terminal extension. The recombinant DNA was used for transformation of the GS115 strain of Pichia pastoris. The heterologous expression level obtained was about 20 mg/l. The receptor was extracted from membrane fraction and was purified by metal-affinity and ion-exchange chromatography. The active receptors were isolated by alprenolol-sepharose CL-4B. The resulting level of purified human beta2-adrenergic receptor was approximately 1 mg per liter of culture. The homogeneity of the protein sample was confirmed by a dynamical light scattering analysis of the receptor's micellar solution. PMID- 22670528 TI - [Crystallographic and NMR spectroscopic protein structures: the inter-residue contacts]. AB - Inter-residue pair contacts have been analyzed in detail for the four pairs of protein structures determined both by X-ray analysis (X-ray) and nuclear magnetic resonance (NMR). At contact distances < or = 4.0 angstroms in the four NMR structures the overall number of pair contacts are less by 4-9% and pair contacts are in average shorter by 0.02-0.16 angstroms than those in corresponding X-ray structures. In each of four structure pairs 83-94% of common pair contacts are formed by the same residues in both structures and rest 6-17% ones are longer own pair contacts formed by the different residues in the NMR and X-ray structures. The amount of the longer own contacts is higher in the X-ray structure of the pair. In the each NMR structure there are three types of common pair contacts, which are shorter, longer or equal length in comparison with identical pair contacts in the X-ray structure of the same protein. The methodological different shortened common pair contacts predominate in the known distant dependence of the inter-residue contact densities of the 60-61 pair of the NMR/X-ray structure. Among four pairs analyzed the contact shortening proceeds upon the energy minimization of the crambin NMR structure and upon the resolving by the program X PLOR with decreased atom van der Waals radius of the NMR structures of ubiquitin, hen lysozyme and monomeric hemoglobin. An extent of the NMR contact shortening decreased as the amount of NMR information upon the calculation of the NMR structures increased. Among 60-61 pairs of NMR/X-ray structures the main difference between alpha-helical and beta-structural proteins on the inter residue distant dependence of the average contact densities arises from the strong alpha/beta difference in the local backbone geometry. PMID- 22670529 TI - [Structure-functional organization of eukaryotic high-affinity copper importer CTR1 determines its ability to transport copper, silver and cisplatin]. AB - It was shown recently, that high affinity Cu(I) importer eukaryotic protein CTR1 can also transport in vitro abiogenic Ag(I) ions and anticancer drug cisplatin. At present there is no rational explanation how CTR1 can transfer platinum group, which is different by coordination properties from highly similar Cu(I) and Ag(I). To understand this phenomenon we analyzed 25 sequences of chordate CTR1 proteins, and found out conserved patterns of organization of N-terminal extracellular part of CTR1 which correspond to initial metal binding. Extracellular copper-binding motifs were qualified by their coordination properties. It was shown that relative position of Met- and His-rich copper binding motifs in CTR1 predisposes the extracellular CTR1 part to binding of copper, silver and cisplatin. Relation between tissue-specific expression of CTR1 gene, steady-state copper concentration, and silver and platinum accumulation in organs of mice in vivo was analyzed. Significant positive but incomplete correlation exists between these variables. Basing on structural and functional peculiarities of N-terminal part of CTR1 a hypothesis of coupled transport of copper and cisplatin has been suggested, which avoids the disagreement between CTR1-mediated cisplatin transport in vitro, and irreversible binding of platinum to Met-rich peptides. PMID- 22670530 TI - [Molecular dynamics simulation of the tubulin dimer with cytostatics]. AB - Colchicin, podophylotoxin and indibulin are natural cytostatics that are used in the treatment of neoplasms. But applications of those compounds are rather restricted due to the high toxicity and low specificity. It seems very promising to investigate possibility to design new analogs of the above mentioned drugs that will possess higher cytostatic activity and less toxicity. For this purpose we see computer modeling experiments of tubulin and above mentioned compounds interaction as a powerful approach to design new artificial cytostatics with desired properties. In the current study the CHARMM software of protein-ligand interaction molecular dynamics method has been used. Particularly the following strategy has been applied. Molecules of the cytostatits have been positioned at several random positions around binding sites of tubulin and after energy minimization several binding sites have been identified on the tubulin macromolecule. In these binding sites structural changes that may be responsible for tubulin polymerization have been detected. PMID- 22670531 TI - [Furanosidase superfamily: search of homologues]. AB - The furanosidase superfamily contains GH32, GH43, GH62, GH68, GH117, DUF377, and DUF1861 families of glycoside hydrolases and their homologues. Catalytic domains of these families have five-bladed beta-propeller tertiary structure. Iterative screening of the protein database allowed to support their relationship as well as evolutionary connections with domains from GH33 and GH93 families of glycoside hydrolases. The latter two have structure of the six-bladed beta-propeller. Among revealed homologues we found 441 unclassified proteins. These proteins are combined into 39 groups based on homology: FURAN1-FURAN39. FURAN8 and FURAN36 can be considered as separate subfamilies within GH43 and GH32 families of glycoside hydrolases, respectively. The remaining 37 groups are new families of hypothetical glycoside hydrolases. PMID- 22670533 TI - Holding steady: maintaining financial viability with Medicare. PMID- 22670532 TI - [Draft macronuclear genome of a ciliate Euplotes crassus]. AB - Basic bioinformatical analysis of the draft Euplotes crassus macronuclear genome and transcriptome suggests that more than a quarter of E. crassus genes contain several exons. A large fraction of all introns is formed by "tiny" introns having length 20-30 bp. Analysis of the transcriptome revealed 63 possible cases of alternative splicing, and also 14 introns with non-standard splicing sites. About 2000 hypothetical genes do not have homologs in other ciliates, and since most of them have the closest homologs in bacterial genomes, they are likely an artifact of the sample preparation. Comparison of the E. crassus genome to the genomes of other ciliates showed an expansion of the same gene families, responsible for the free-living heterotrophic lifestyle. PMID- 22670534 TI - Doing more with less: making the most of resources in a lean world. PMID- 22670535 TI - Accountable care and patient-centered medical homes: steps to creating value based healthcare. PMID- 22670536 TI - Productivity: doing more with less. PMID- 22670538 TI - Management: seeing the big picture. PMID- 22670537 TI - Leadership: avoiding common leadership mistakes. PMID- 22670539 TI - The importance of failing forward. All of us will fail and make mistakes, but how can they benefit us and our organizations? PMID- 22670540 TI - Improving outcomes through pharmacy. Use of clinical pharmacists in the acute care setting can offer benefits to patients, organization. PMID- 22670541 TI - Meeting the healthcare needs of special needs children. Children's Village emerges and sustains through innovation, collaboration. PMID- 22670542 TI - The Supreme Court and healthcare. Justices may rule in June on constitutionality of health law. PMID- 22670543 TI - Your career is a marathon. Making smart choices during each career phase will allow you to go the distance. PMID- 22670544 TI - The expanding role of compensation committee. Responsibilities can include performance evaluation and succession planning. PMID- 22670545 TI - When there is no doctor in the house. Strategies for accommodating a physician shortage. PMID- 22670546 TI - Hospital CEO survey: progress on preparing for healthcare reform. PMID- 22670547 TI - Considerations for healthcare executive-supplier interactions. PMID- 22670548 TI - The second renaissance of hyperbaric medicine: indications revisited. PMID- 22670549 TI - Hyperbaric oxygen therapy reduces COX-2 expression in a dimethylhydrazine-induced rat model of colorectal carcinogenesis. AB - BACKGROUND: A better understanding of oncogenesis mechanisms should result in more effective approaches to colorectal cancer (CRC) treatment and prevention. Hyperbaric oxygen (HBO2) therapy is indicated as adjuvant treatment for infectious diseases as well as hypoxic and inflammatory lesions. The anti inflammatory effect of HBO2 could reduce colorectal carcinogenesis. METHODS: 48 Wistar rats were randomly divided into the following groups: * G1 - control; * G2 - HBO2 treatment; * G3 - 1,2-dimethylhydrazine (DMH) injection only; * G4 - DMH injection and HBO2 treatment. These groups were further randomly divided into two subgroups: a. euthanasia at six weeks; and. b. euthanasia at 12 weeks. Animals belonging to G2 and G4 were subjected to 15 HBO2 sessions, performed every 24 hours at 2.0 atm absolute pressure, 90 minutes each. Cancer was induced via intraperitoneal injection of DMH in G3 and G4. The aberrant crypt foci index (ACFi), the cell nuclear antigen index (PCNA) and the cyclooxygenase-2 index (iCOX-2) were determined. RESULTS: After DMH administration, ACFi increased and was higher in subgroups euthanized at six weeks than in those sacrificed at 12 weeks (p < 0.001). HBO2 alone (G2) did not affect ACFi (p > or = 0.05). Larger increases of PCNA were detected in G2 versus G3 (p < 0.05). Comparison between G4 and control group mice revealed no differences in PCNA (p > 0.05). COX-2 was overexpressed in G3 (p < 0.0001) compared to G4. CONCLUSION: COX-2 expression was "induced" by DMH and reverted to a "wild"-type level of expression upon exposure to HBO2. PMID- 22670550 TI - Lung function before and after oxygen diving: a randomized crossover study. AB - RATIONALE: Breathing oxygen with a partial pressure of > 50 kPa can cause pulmonary oxygen toxicity (POT). Diffusing capacity for carbon monoxide (DL(CO)) is thought to be a more sensitive indicator of POT than vital capacity (VC). Because diffusing capacity can be measured more specifically using nitric oxide (DL(NO)), we hypothesized that DL(NO) is better able to monitor and exclude POT than DL(CO). OBJECTIVE: To compare changes in lung function after oxygen and air dives which include measurement of DL(NO) and DL(CO). METHOD: Eleven healthy male divers (mean age 27.5 +/- 3.1 years) made two immersed dives to 150 kPa for three hours on two separate days, during which they randomly breathed 100% oxygen or air. VC, DL(NO) and DL(CO) were measured six times during a 26-hour period on both days and on a third non-diving day. RESULTS: There were no significant changes in DL(CO), DL(NO) or other diffusing capacity or spirometric parameters after either type of dive. CONCLUSION: Lung function after a single three-hour oxygen dive at a pO2 of approximately 150 kPa is comparable to that after an air dive at the same depth and duration. This suggests that such an oxygen dive does not induce detectable signs of POT. Our hypothesis that DL(NO) is more sensitive than DL(CO) for detection of POT could not be tested because the oxygen exposure did not affect either parameter. PMID- 22670551 TI - Per-capita claims rates for decompression sickness among insured Divers Alert Network members. AB - Decompression sickness (DCS) in recreational diving is a rare and usually self limiting injury, but permanent disability can occur. Incidence rate estimates are difficult to establish because the number of divers at risk is usually unknown in population samples with well-documented DCS. We estimated the annual per-capita DCS incidence rates for 2000-2007 based on insurance claims submitted by members of the Divers Alert Network (DAN), Durham, N.C., with dive accident insurance. The overall per-capita DCS claims rate (DCR) was 20.5 per 10,000 member-years. Based on the age-adjusted DCR, males submitted 28% more claims than females. Male to-female difference was greatest between 35 and 40 years of age and disappeared by the mid-50s. Highest rates were observed in the 30- to 39-year age category, after which DCR declined with increasing age. Highest yearly DCR was estimated in 2002. Insurance dropout rate was greater among those who had DCS in the first year of their insurance compared to those who did not have DCS in their first year. PMID- 22670553 TI - Intracranial abscess. PMID- 22670552 TI - Hyperbaric oxygen treatment for skin flap necrosis after a mastectomy: a case study. AB - The rate of complications in immediate breast reconstruction is in 15% to 20% due to partial loss of the mastectomy skin flaps. In the case of skin necrosis or ischemia, a therapy that reduces skin loss could be of additional benefit. Hyperbaric oxygen has been used to treat compromised flaps and grafts, an indication recognized and reimbursed according to the Undersea and Hyperbaric Medical Society (UHMS). So far, hyperbaric oxygen has not been previously reported as therapy for full-thickness breast skin flap necrosis on patients with a direct reconstruction with silicone implants after a skin-sparing mastectomy. This report presents such a case, in which a 52-year-old woman carrier of the BRCA2 mutation gene was successfully treated with hyperbaric oxygen therapy. PMID- 22670554 TI - Clostridial myonecrosis (gas gangrene). PMID- 22670555 TI - Necrotizing soft tissue infections. PMID- 22670556 TI - Osteomyelitis (refractory) with literature review supplement. PMID- 22670557 TI - Hyperbaric oxygen therapy for idiopathic sudden sensorineural hearing loss. AB - Idiopathic sudden sensorineural hearing loss (ISSHL) is the newest indication approved by the Undersea and Hyperbaric Medical Society's Hyperbaric Oxygen Therapy Committee. Idiopathic sudden sensorineural hearing loss appears to be characterized by hypoxia in the perilymph and therefore the scala tympani and the organ of Corti. A review of the literature reveals more than 100 publications evaluating the use of hyperbaric oxygen (HBO2) for the treatment of ISSHL, including eight randomized controlled trials. The best and most consistent results are obtained when HBO2 is initiated within two weeks of symptom onset and combined with corticosteroid treatment. The average hearing gain is 19.3 dB for moderate hearing loss and 37.7 dB for severe cases. This improvement brings hearing deficits from the moderate/severe range into the slight/no impairment range. This is a significant gain that can markedly improve a patient's quality of life, both clinically and functionally. PMID- 22670558 TI - New HBO2 evidence web site is open. PMID- 22670559 TI - Protein transport through a narrow solid-state nanopore at high voltage: experiments and theory. AB - We report experimentally the transport of an unfolded protein through a narrow solid-state nanopore of 3 nm diameter as a function of applied voltage. The random coil polypeptide chain is larger than the nanopore. The event frequency dependency of current blockades from 200 to 750 mV follows a van't Hoff-Arrhenius law due to the confinement of the unfolded chain. The protein is an extended conformation inside the pore at high voltage. We observe that the protein dwell time decreases exponentially at medium voltage and is inversely proportional to voltage for higher values. This is consistent with the translocation mechanism where the protein is confined in the pore, creating an entropic barrier, followed by electrophoretic transport. We compare these results to our previous work with a larger pore of 20 nm diameter. Our data suggest that electro-osmotic flow and protein adsorption on the narrowest nanopore wall are minimized. We discuss the experimental data obtained as compared with recent theory for the polyelectrolyte translocation process. This theory reproduces clearly the experimental crossover between the entropic barrier regime with medium voltage and the electrophoretic regime with higher voltage. PMID- 22670560 TI - Living with the BRCA genetic mutation: an uncertain conclusion to an unending process. AB - Women carrying a BRCA1 or BRCA2 genetic mutation have an up to 80% lifetime risk of developing breast cancer. It is especially important to understand the experiences of these women, as their lives are permeated with the threat of cancer. This qualitative study examined the experiences of six young women of reproductive age (age < 45 years) who were identified as carriers. The analysis of the semi-structured interviews inspired by grounded theory methodology, showed that participants experienced the same type of uncertainty demonstrated by women who have already been diagnosed with breast cancer. PMID- 22670561 TI - Acute reduction of anandamide-hydrolase (FAAH) activity is coupled with a reduction of nociceptive pathways facilitation in medication-overuse headache subjects after withdrawal treatment. AB - OBJECTIVES: We investigated (1) a possible relationship between the functional activity of the endocannabinoid system and the facilitation of pain processing in migraineurs with medication-overuse headache, and (2) the effect of withdrawal treatment on both. BACKGROUND: The endocannabinoid system antinociception effect includes prevention of nociceptive pathways sensitization. The sensitization of the pain pathways has been demonstrated to be pivotal in the development and maintenance of chronic form of migraine, including medication-overuse headache. METHODS: We used the temporal summation threshold of the nociceptive withdrawal reflex to explore the spinal cord pain processing, and the platelet activity of the enzyme fatty acid amide hydrolase to detect the functional state of the endocannabinoid system in 27 medication-overuse headache subjects before and 10 and 60 days after a standard withdrawal treatment and compared results with those of 14 controls. RESULTS: A significantly reduced temporal summation threshold and increased related pain sensation was found in subjects before withdrawal treatment when compared with controls. A significant fatty acid amide hydrolase activity reduction coupled with a significant improvement (reduction) in facilitation of spinal cord pain processing (increase in temporal summation threshold and reduction in related pain sensation) was found in medication overuse headache subjects at both 10 and 60 days after withdrawal treatment when compared with medication-overuse headache subjects before withdrawal treatment. CONCLUSIONS: We demonstrated a marked facilitation in spinal cord pain processing in medication-overuse headache before withdrawal treatment when compared with controls. Furthermore, the acute reduction of the fatty acid amide hydrolase activity coupled with a reduction of the facilitation in pain processing immediately (10 days) after withdrawal treatment and its persistence 60 days after withdrawal treatment could represent the consequence of a mechanism devoted to acutely reduce the degradation of endocannabinoids and aimed to increase the activity of the endocannabinoid system that results in an antinociceptive effect. PMID- 22670562 TI - Antifungal activity of Moroccan medicinal plants against citrus sour rot agent Geotrichum candidum. AB - AIMS: The aim of this work was to find an alternative to the chemical fungicides currently used in the control of Geotrichum candidum, the causal agent of citrus sour rot. METHODS AND RESULTS: Minimal inhibition concentrations (MIC) and minimal fungicidal concentrations (MFC) were determined using agar dilution method. The methanol extracts of Cistus villosus, Ceratonia siliqua and Halimium umbellatum exhibited strong antifungal activity with MIC values ranged between 0.156 and 1.25 mg ml(-1), and MFC values ranged between 2.5 and 5 mg ml(-1). Incidence of sour rot was lowered to 0.00, 3.33 and 11.66% when mandarin fruit was treated with C. villosus, C. siliqua and H. umbellatum methanol extracts at 50 mg ml(-1), respectively, compared with 95% in the control. CONCLUSIONS: Cistus villosus, C. siliqua and H. umbellatum methanol extracts successfully reduced the disease incidence caused by G. candidum, and no phytotoxic effects were recorded on citrus fruit. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings suggest that C. villosus, C. siliqua and H. umbellatum plants may be useful and effective agents for control of citrus sour rot. Such natural products therefore represent a sustainable alternative to the use of synthetic fungicides. PMID- 22670563 TI - Designing higher surface area metal-organic frameworks: are triple bonds better than phenyls? AB - We have synthesized, characterized, and computationally validated the high Brunauer-Emmett-Teller surface area and hydrogen uptake of a new, noncatenating metal-organic framework (MOF) material, NU-111. Our results imply that replacing the phenyl spacers of organic linkers with triple-bond spacers is an effective strategy for boosting molecule-accessible gravimetric surface areas of MOFs and related high-porosity materials. PMID- 22670564 TI - Matrix effects in analysis of beta-agonists with LC-MS/MS: influence of analyte concentration, sample source, and SPE type. AB - The synergistic influences of analyte concentration, sample source, and solid phase extraction (SPE) type on matrix effects in the multiresidue analyses of eight beta-agonists with LC-ESI-MS/MS were evaluated. Porcine muscle and liver extracts and urine from diverse sources were purified by strong or mixed-mode cation exchange and molecularly imprinted polymer SPE cartridges, respectively. Three spiked concentrations (2, 10, and 20 ng/mL) of eight beta-agonists in the purified matrices and the different sample sources were analyzed. The results show that for most beta-agonists there are significant differences in matrix effects between analyte concentrations or sample sources (P < 0.05), whereas there is no significant difference in matrix effects between different SPE cartridges (P > 0.05). Results from main effects testing indicated that analyte concentration was the main effector. PMID- 22670565 TI - Nitric oxide augments oridonin-induced efferocytosis by human histocytic lymphoma U937 cells via autophagy and the NF-kappaB-COX-2-IL-1beta pathway. AB - We previously demonstrated that oridonin-induced autophagy enhanced efferocytosis (phagocytosis of apoptotic cells) by macrophage-like U937 cells through activation of the inflammatory pathways. In this study, exposure of U937 cells to 2.5 MUM oridonin caused up-regulation of inducible nitric oxide synthase (iNOS) expression and continuous endogenous generation of nitric oxide (NO), which was reversed by pre-treatment with the inhibitors of nitric oxide synthase 1400 W (dihydrochloride) or L-NAME (hydrochloride). NO donor sodium nitroprusside (SNP) and efferocytosis irritant lipopolysaccharide (LPS) could also exert NO generation and iNOS expression. Moreover, oridonin-induced stimulation of efferocytosis was significantly suppressed by 1400 W or L-NAME. In addition, 1400 W or L-NAME impaired oridonin-induced autophagy. Inhibition of autophagy with 3 methyladenine (3MA) or Beclin-1 siRNA attenuated the uptake of apoptotic cells with a slight increase in the production of NO. The pro-inflammatory cytokine interleukin-1beta (IL-1beta) has been reported to be involved in oridonin-induced efferocytosis in U937 cells and interact with NO to contribute to inflammatory responses. 1400 W or L-NAME blocked the secretion of IL-1beta and the activation of NF-kappaB and COX-2. Provision of SNP or LPS in place of oridonin resulted in the similar enhancement of efferocytosis, autophagy, the release of IL-1beta and the expression of signal protein. NO augmented the oridonin-induced efferocytosis by mediating autophagy and activating the NF-kappaB-COX-2-IL-1beta pathway. Inhibition of NF-kappaB or COX-2 in turn decreased the production of NO and the expression of iNOS. There exists a positive feedback loop between NO generation and NF-kappaB-COX-2-IL-1beta pathway. PMID- 22670566 TI - Active cocaine use is associated with lack of HIV-1 virologic suppression independent of nonadherence to antiretroviral therapy: use of a rapid screening tool during routine clinic visits. AB - Clarifying the relationship between illicit drug use and HIV-1 virologic suppression requires characterization of both illicit drug use activity and adherence to antiretroviral therapy (ART). We developed a rapid clinical questionnaire to assess prior 7-day illicit drug use and ART adherence in a cross sectional study among 1777 HIV-infected persons in care. Of these, 76% were male, 35% were African-American, and 8% reported injection drug use as their probable route of HIV-1 infection. Questionnaire-reported frequencies of cocaine and marijuana use within the previous 7 days were 3.3% and 12.1%, respectively. Over three quarters (77.8%) of participants were on ART, of whom 69.7% had HIV-1 virologic suppression (HIV-1 RNA<48 copies/mL). Univariate analyses revealed that compared to no use, cocaine and marijuana use were both associated with missed ART doses (P<0.01). Multivariable logistic regression analysis adjusting for nonadherence demonstrated that cocaine use was independently associated with failing to achieve virologic suppression (adjusted odds ratio (aOR): 0.46; 95% confidence interval (95% CI): 0.22-0.98) but marijuana use was not (aOR: 1.08; 95% CI: 0.72-1.62). This result strengthens the evidence of a direct effect of cocaine on virologic control, independent of nonadherence to ART. PMID- 22670567 TI - Robust classification of functional and quantitative image data using functional mixed models. AB - This article introduces new methods for performing classification of complex, high-dimensional functional data using the functional mixed model (FMM) framework. The FMM relates a functional response to a set of predictors through functional fixed and random effects, which allows it to account for various factors and between-function correlations. The methods include training and prediction steps. In the training steps we train the FMM model by treating class designation as one of the fixed effects, and in the prediction steps we classify the new objects using posterior predictive probabilities of class. Through a Bayesian scheme, we are able to adjust for factors affecting both the functions and the class designations. While the methods can be used in any FMM framework, we provide details for two specific Bayesian approaches: the Gaussian, wavelet based FMM (G-WFMM) and the robust, wavelet-based FMM (R-WFMM). Both methods perform modeling in the wavelet space, which yields parsimonious representations for the functions, and can naturally adapt to local features and complex nonstationarities in the functions. The R-WFMM allows potentially heavier tails for features of the functions indexed by particular wavelet coefficients, leading to a down-weighting of outliers that makes the method robust to outlying functions or regions of functions. The models are applied to a pancreatic cancer mass spectroscopy data set and compared with other recently developed functional classification methods. PMID- 22670572 TI - Can deficits in empathy after head injury be improved by compassionate imagery? AB - Severe head injury (SHI) can result in problems in empathising, which in turn is associated with social difficulties. Compassionate imagery can increase compassion in non-brain injured people and can alter how they relate to themselves and others. This preliminary study investigates whether compassionate imagery can increase empathy in those with low empathy after SHI. A between-group repeated measures design was used wth 24 participants with severe SHI and low empathy, randomly allocated to a single treatment session of compassionate imagery or a control condition of relaxation. Empathy, self-compassion and relaxation were assessed pre- and post-intervention and fear of compassion pre intervention as a potential covariate. A group effect of compassionate imagery on empathy was not found, F(1, 21) = 0.12, p = .73. A non-specific increase in self compassion approached significance, T = 78.00, p = 0.07, r = -.26. Fear of compassion did not correlate significantly with changes in self-compassion or empathy. Demographic and injury factors associated with SHI that may impact on treatment effectiveness are discussed. Further research that takes these factors into account is warranted. PMID- 22670573 TI - Risk factors for developing post-traumatic stress disorder following childbirth: a systematic review. AB - BACKGROUND: Approximately 1-2% of women suffer from post-traumatic stress disorder (PTSD) postnatally. This review aims to elucidate how women at risk can be identified. METHODS: A systematic search of the published literature was carried out using the MEDLINE database (November 2003 to 29 October 2010) with both MeSH terms and free text. Thirty-one studies were considered appropriate for qualitative synthesis. Articles were included on the basis of (a) publication pertaining to PTSD following childbirth, (b) study carried out in Western Europe and (c) publication written in English. The results were primarily based on observational studies. The literature was thoroughly read and results were compiled. Furthermore, a novel quality rating system was employed to minimize the impact of bias. RESULTS: Subjective distress in labor and obstetrical emergencies were the most important risk factors. Infant complications, low support during labor and delivery, psychological difficulties in pregnancy, previous traumatic experiences, and obstetrical emergencies were identified as risk factors. CONCLUSIONS: We have identified factors both strongly associated and non associated with PTSD following childbirth. While the literature is limited by methodological shortcomings, a hypothesis regarding the development of PTSD is outlined, and recommendations with respect to screening and future research are provided. PMID- 22670574 TI - Intervention for aggressive victims of school bullying in Hong Kong: a longitudinal mixed-methods study. AB - The distinction between aggressive and passive victims of school bullying is well documented. Aggressive victims exhibit restlessness and hot-temperedness, are easily provoked, and take revenge when irritated, whereas passive victims are quiet and timid when attacked or insulted and withdraw rather than retaliate. To date, there has been no evidence-based evaluative study examining interventions designed specifically to reduce aggressive victimization, and neither has there been an inclusive assessment screening of high-risk aggressive victims prior to intervention. This study addressed these research gaps by employing multi-stage assessment procedures and a mixed-mode methodology in a one-year longitudinal design. Data were collected from student self-reports, parent and teacher rating scales, and individual structured interviews with students, parents and teachers. A total of 269 potential high-risk aggressive victims were identified from among 5,089 schoolchildren, 68 of whom were screened out and randomly assigned to 10 treatment groups, with 39 completing a one-year follow-up study. Multivariate analysis of variance identified significant improvements in physical and verbal victimization (F(2,47, 93.99) = 10.73, p < 0.01), verbal victimization (F(2.74, 104.14) = 12.80, p < 0.01) and social exclusion scores at the three follow-up assessments compared to the pre-treatment scores, and the qualitative results were consistent, showing participants' cognition, emotion, and behavior to have been positively reconstructed by the group intervention. The consistent quantitative and qualitative results confirm that the cognitive-behavioral group therapy program reported herein is effective in reducing aggressive victims' anxious and depressed emotions and reactive cognition. PMID- 22670568 TI - P/Q-type calcium channel modulators. AB - P/Q-type calcium channels are high-voltage-gated calcium channels contributing to vesicle release at synaptic terminals. A number of neurological diseases have been attributed to malfunctioning of P/Q channels, including ataxia, migraine and Alzheimer's disease. To date, only two specific P/Q-type blockers are known: both are peptides deriving from the spider venom of Agelenopsis aperta, omega agatoxins. Other peptidic calcium channel blockers with activity at P/Q channels are available, albeit with less selectivity. A number of low molecular weight compounds modulate P/Q-type currents with different characteristics, and some exhibit a peculiar bidirectional pattern of modulation. Interestingly, there are a number of therapeutics in clinical use, which also show P/Q channel activity. Because selectivity as well as the exact mode of action is different between all P/Q-type channel modulators, the interpretation of clinical and experimental data is complicated and needs a comprehensive understanding of their target profile. The situation is further complicated by the fact that information on potency varies vastly in the literature, which may be the result of different experimental systems, conditions or the splice variants of the P/Q channel. This review attempts to provide a comprehensive overview of the compounds available that affect the P/Q-type channel and should help with the interpretation of results of in vitro experiments and animal models. It also aims to explain some clinical observations by implementing current knowledge about P/Q channel modulation of therapeutically used non-selective drugs. Chances and challenges of the development of P/Q channel-selective molecules are discussed. PMID- 22670576 TI - Young person's epilepsy transition clinic. PMID- 22670575 TI - Folic acid functionalized nanoparticles for enhanced oral drug delivery. AB - The oral absorption of drugs that have poor bioavailability can be enhanced by encapsulation in polymeric nanoparticles. Transcellular transport of nanoparticle encapsulated drug, possibly through transcytosis, is likely the major mechanism through which nanoparticles improve drug absorption. We hypothesized that the cellular uptake and transport of nanoparticles can be further increased by targeting the folate receptors expressed on the intestinal epithelial cells. The objective of this research was to study the effect of folic acid functionalization on transcellular transport of nanoparticle-encapsulated paclitaxel, a chemotherapeutic with poor oral bioavailability. Surface functionalized poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles loaded with paclitaxel were prepared by the interfacial activity assisted surface functionalization technique. Transport of paclitaxel-loaded nanoparticles was investigated using Caco-2 cell monolayers as an in vitro model. Caco-2 cells were found to express folate receptor and the drug efflux protein, p-glycoprotein, to high levels. Encapsulation of paclitaxel in PLGA nanoparticles resulted in a 5 fold increase in apparent permeability (Papp) across Caco-2 cells. Functionalization of nanoparticles with folic acid further increased the transport (8-fold higher transport compared to free paclitaxel). Confocal microscopic studies showed that folic acid functionalized nanoparticles were internalized by the cells and that nanoparticles did not have any gross effects on tight junction integrity. In conclusion, our studies indicate that folic acid functionalized nanoparticles have the potential to enhance the oral absorption of drugs with poor oral bioavailability. PMID- 22670577 TI - The multifunctionality of human Vgamma9Vdelta2 gammadelta T cells: clonal plasticity or distinct subsets? AB - The dominant subset of gammadelta T cells in human peripheral blood expresses Vgamma9 paired with Vdelta2 as variable TCR elements. Vgamma9Vdelta2 T cells recognize pyrophosphates derived from the microbial non-mevalonate isoprenoid biosynthesis pathway at pico- to nanomolar concentrations. Structurally related pyrophosphates are generated in eukaryotic cells through the mevalonate pathway involved in protein prenylation and cholesterol synthesis. However, micromolar concentrations of endogenous pyrophosphates are required to be recognized by Vgamma9Vdelta2 T cells. Such concentrations are not produced by normal cells but can accumulate upon cellular stress and transformation. Therefore, many tumour cells are susceptible to gammadelta T cell-mediated lysis owing to the overproduction of endogenous pyrophosphates. This explains why Vgamma9Vdelta2 T cells contribute to both anti-infective and anti-tumour immunity. Ex vivo analysed Vgamma9Vdelta2 T cells can be subdivided on the basis of additional surface markers, including chemokine receptors and markers for naive and memory T cells. At the functional level, Vgamma9Vdelta2 T cells produce a broad range of cytokines, display potent cytotoxic activity, regulate alphabeta T cell responses, and - quite surprisingly - can act as professional antigen-presenting cells. Thus, an exceptional range of effector functions has been assigned to a population of T cells, which all recognize invariant exogenous or endogenous pyrophosphates that are not seen by any other immune cell. Here, we discuss whether this plethora of effector functions reflects the plasticity of individual Vgamma9Vdelta2 T cells or can be assigned to distinct subsets. PMID- 22670578 TI - TaCKX6-D1, the ortholog of rice OsCKX2, is associated with grain weight in hexaploid wheat. AB - The cytokinin oxidase/dehydrogenase (CKX) gene plays a principal role in controlling cytokinin levels and has been shown to be a major quantitative trait locus (QTL) affecting grain number in rice. However, the function and evaluation of the haplotypes of the wheat CKX gene have yet to be illustrated. In this study, TaCKX6-D1, a wheat ortholog of rice OsCKX2, was cloned and its haplotype variants were determined to be significantly associated with the 1000-grain weight on the basis of linkage mapping, association analysis and gene expression analysis. Five TaCKX6-D1 haplotypes, designated a-e, were identified. An indel marker was developed to identify haplotype a, which was associated with higher grain weight. Haplotype a showed decreased expression relative to haplotype b in seeds at 8 d after pollination. Sequence variations among modern cultivars, landraces and wild species suggest a significant domestication signature at the TaCKX6-D1 locus in Chinese wheat germplasm. TaCKX6-D1 may serve as a useful gene for the breeding of high-yielding wheat. A strategy for allele mining and utilization of TaCKX6-D1 was proposed. Our study also sheds light on the mechanisms of grain development and domestication of wheat, as well as the functional divergence of orthologs in comparative genomics. PMID- 22670579 TI - Overestimation of umbilical cord coiling index with segmental versus total length assessment. AB - The umbilical cord is the only communication between the fetus and the placenta and, not surprisingly, lesions or conditions affecting it may have detrimental effects in both. One important feature of the umbilical cord is its coiling index (UCI), with hypo- and hypercoiling being associated with fetal thrombotic vasculopathy, intolerance of labor, intrauterine growth restriction, cord stricture, thrombosis of cord and chorionic blood vessels, and fetal demise. It is essential that every placenta report include the UCI. The UCI could also be assessed prenatally, but there is currently no way of accurately assessing the entire length of the umbilical cord. The aim of this study was to compare UCI measured in a segment of cord 10 cm long (UCI-10) and over its total length (UCI T). One hundred fifty consecutive placenta reports in which both measurements were recorded were retrieved from the files and analyzed. Gestational age ranged from 16 to 42 weeks, with a mean of 33.67 +/- 5.96 weeks and a median of 36 weeks. Mean UCI-10 was 0.4360 +/- 0.2625 coils/cm and mean UCI-T was 0.3530 +/- 0.2022 coils/cm; the difference between these measurements was highly statistically significant (P < 0.0001). Counting the number of umbilical cord coils in 10 cm led to an overestimation of the UCI-T by 23.5%; it can be concluded, therefore, that the latter should be used. PMID- 22670580 TI - The changing role of hypertension societies: shifting gears in Italy. PMID- 22670581 TI - Obesity and hypertension in cardiac hypertrophy: two sides of the same coin? PMID- 22670582 TI - Renal denervation and treatment of hypertension. AB - Cardiovascular diseases kill more people each year than any other diseases. In 2008, 7.3 million people died of ischaemic heart disease, 6.2 million from stroke or another form of cerebrovascular disease. Hypertension affects about 1 billion people worldwide and is a major risk factor for many cardiovascular diseases, including coronary heart disease and stroke. In contrast, our knowledge in regard to the underlying molecular mechanisms remains incomplete and, as a consequence, it is difficult if not impossible to efficiently treat the most affected patients. While the development and application of novel pharmacological agents in combination with lifestyle changes have been applied in Western developed countries to a large number of patients, a significant number of individuals fail to respond. Recently, several novel approaches have been developed including a minimally invasive catheter-based renal nerve ablation technique and some of the consequences will be highlighted in this brief review article. This will include the discussion of previous attempts to denervate the renal arteries as well as the significant improvements achieved when catheter-based interventions are applied. PMID- 22670583 TI - Left heart morphology and function in primary aldosteronism. AB - Primary aldosteronism is the most frequent cause of secondary hypertension, accounting for up to 11% of cases in selected populations. Patients affected by primary aldosteronism have shown higher prevalence of cardiovascular and cerebrovascular events compared with patients with essential hypertension, despite similar blood pressure levels. Several studies have been performed over past years aiming to explain these data; many of these evaluated echocardiographic differences in hypertension-related cardiac organ damage between primary aldosteronism and essential hypertension. This article summarizes the present knowledge about structural and functional alteration of the human left heart in primary aldosteronism. PMID- 22670584 TI - The role of irbesartan in the treatment of patients with hypertension: a comprehensive and practical review. AB - Irbesartan is an orally active angiotensin II type 1 receptor antagonist (angiotensin receptor blocker [ARB]) whose pharmacological profile differs significantly from those of many other compounds of the same class. In particular, according to its pharmacokinetic and pharmacodynamic profile, irbesartan has a high bioavailability, a long duration of action and a small potential for pharmacological interactions due to the nature of the enzymatic pathway involved in its metabolic process. Morbidity data with irbesartan have been mainly accumulated in patients with renal impairment where the drug has demonstrated the most remarkable evidence of efficacy among the ARBs class, regardless of the stage of the renal disease (from early to late) and the length of the observational period. The efficacy of irbesartan has also been demonstrated in patients with left ventricular hypertrophy and congestive heart failure. The drug is indicated for the treatment of hypertension and renal impairment in patients with type 2 diabetes mellitus (T2D) and hypertension, and its tolerability and safety profile have been extensively investigated and reported to be similar to placebo. From the pharmacoeconomic point of view, treating patients with T2D, hypertension and overt nephropathy using irbesartan was both a cost- and life-saving procedure compared with the use of amlodipine and standard antihypertensive treatment in an Italian setting. The role of irbesartan in the management of hypertension with or without T2D and renal impairment is clearly recognized by national and international guidelines and largely acknowledged by the medical community according to the efficacy of the drug in the prevention of cardiovascular risk in addition to and beyond kidney prevention. PMID- 22670585 TI - Prevalence of left ventricular hypertrophy and determinants of left ventricular mass in obese women. AB - BACKGROUND: Obesity is frequently associated with left ventricular hypertrophy (LVH), a condition leading to an increased cardiovascular risk. AIM: The objective of this study was to evaluate the prevalence of LVH in a cohort of obese women, with a main focus on the anthropometric and clinical parameters that are associated with an increased left ventricular mass (LVM). METHODS: The study was performed in 166 obese female patients. LVM was measured by echocardiography. The influence of various parameters on LVM was assessed by multivariate analysis. RESULTS: The prevalence of LVH was drastically different depending on the type of indexed LVM, being 19.9% when the LVM was indexed for body surface area and 72.3% when indexed for height. Age, duration of obesity, weight, waist-to-hip ratio, pulse pressure and hypertension retained an independent direct correlation with the LVM, explaining 39.6% of the overall LVM variability. Among the parameters of the metabolic syndrome, the increase in blood pressure was the main determinant of increased LVM. CONCLUSIONS: By using allometric indexation of LVM for height, the results of our study indicate a high prevalence of LVH in a cohort of obese women. Hypertension, pulse pressure, age, duration of obesity, bodyweight and fat distribution, expressed as waist-to-hip ratio, predict 40% of LVM variation. PMID- 22670586 TI - High blood pressure, overweight and obesity among rural scholars from the Vela Project: a population-based study from South America. AB - BACKGROUND: Many studies have shown that high blood pressure and overweight begins in childhood. Consequently, it is useful to know blood pressure and body mass index (BMI) values from an early age. There are few data about blood pressure control in children and adolescents from rural populations in South America. AIM: The objective of this study was to determine the prevalence of high blood pressure and its association with sedentary habits and overweight/obesity in scholars from a rural population in Argentina. METHODS: The study population for this cross-sectional study was composed of rural children and adolescent scholars from Maria Ignacia Vela. Pre-hypertension and hypertension were defined on the basis of percentiles from the average of three blood pressure measurements taken on a single occasion. In patients with three blood pressure measurements above the 90th percentile, ambulatory blood pressure monitoring was performed to confirm hypertension or pre-hypertension. BMI was categorized by using the 2000 Centers for Disease Control and Prevention growth charts. RESULTS: We studied 334 scholars (aged 5-18 years). Mean age was 11.4 years. In 70% of the subjects, blood pressure had never been measured. The prevalence of high blood pressure was 4.4%. Students with sedentary habits were 3.67-fold more likely to develop high blood pressure than their physically active counterparts (odds ratio [OR] 3.67; 95% CI 1.08, 12.46; p = 0.037). Obese students were more likely to develop hypertension than the students with normal weight (OR = 5.17; 95% CI 1.52, 17.60; p = 0.02). Male students had a 3.4-fold higher risk of developing high blood pressure than females. CONCLUSIONS: In our rural population, the evaluation of blood pressure in children and adolescents is not a routine measure. Our data indicate a low prevalence of high blood pressure. These data could argue differences between rural and urban scholars. Our data demonstrate a close relationship between increased overweight, obesity and sedentary lifestyle with the development of high blood pressure. We emphasize the importance of blood pressure controls and the need to implement programmes to modify sedentary lifestyle in rural populations. PMID- 22670587 TI - Correlation of hypertension with waist circumference in Iranian adults. AB - BACKGROUND: Cardiovascular disease (CVD) is the most important cause of mortality in developed and developing countries. Hypertension is a major risk factor for CVD. Waist circumference (WC) cut-off point is a simple way to recognize risk of developing hypertension. However, there are different cut-off points for different races, including Iranians. AIM: The objective of this article was to determine the association between WC and hypertension as an important cardiovascular risk factor in the Iranian population. METHODS: A total of 850 subjects (430 women and 420 men) older than 18 years, who were residents in the urban and rural areas throughout Arak city, Iran, were included in the present study. WC of subjects was measured to identify its relationship with hypertension. Fasting plasma glucose and lipid profile were also measured. RESULTS: WC cut-off point to predict hypertension was 89 cm and 93 cm for men and women, respectively, by using receiver operator characteristic curve analysis. CONCLUSIONS: The results of our analysis showed that the cut-off point of WC in the Iranian population is greater than other Asians and WC is a strong index to predict hypertension. PMID- 22670589 TI - Restriction analysis of an amplified rodA gene fragment to distinguish Aspergillus fumigatus var. ellipticus from Aspergillus fumigatus var. fumigatus. AB - A previous multidisciplinary study indicated that gliotoxin-producing Aspergillus fumigatus Fresen. isolates from silage commodities mostly belonged to its variant A. fumigatus var. ellipticus Raper & Fennell. Sequence analysis revealed the presence of a single nucleotide polymorphism at five positions in a fragment of the rodA gene (coding for a hydrophobin rodletA protein) between Aspergillus fumigatus var. fumigatus and Aspergillus fumigatus var. ellipticus. A method was developed to distinguish these two types of isolates based on restriction analysis of this rodA gene fragment using the HinfI restriction enzyme. In addition, in silico analysis of 113 rodA gene fragments retrieved from GenBank was performed and confirmed the suitability of this method. In conclusion, the method developed in this study allows easy distinction between A. fumigatus var. fumigatus and its variant ellipticus. In combination with the earlier developed PCR-restriction fragment length polymorphism method of Staab et al. (2009, J Clin Microbiol 47: 2079), this method is part of a sequencing-independent identification scheme that allows for rapid distinction between similar species/variants within Aspergillus section Fumigati, specifically A. fumigatus, A. fumigatus var. ellipticus, Aspergillus lentulus Balajee & K.A. Marr, Neosartorya pseudofischeri S.W. Peterson and Neosartorya udagawae Y. Horie, Miyaji & Nishim. PMID- 22670588 TI - Chemical composition of currant seed extracts and their protective effect on human lymphocytes DNA. AB - On the basis of LC/UV/MS analysis, 35 compounds from the extracts of seeds of black, red, and white currants (2 cultivars of each) were identified. Black currants cultivars contained protocatechuic acid and p-hydroxybenzoic acid, and traces of nitril containing phenolic acids. The presence of synapoyl glucoside was characteristic for cv. Malling Jewel. Sesquiterpenoid glycosides and carboxymethylindol glycosides were present mainly in white and red currant cultivars. Blackcurrant seeds contained higher amounts of flavonoids, especially rutin, isoquercetin, and taxifolin. The currant seed extracts were tested for in vitro protective effect on chromosome aberrations in peripheral human lymphocytes using cytochalasin-B blocked micronucleus (CBMN) assay. The frequency of MN was scored in binucleated cells, and the cultivars of black currants showed the best antioxidant potential. At a concentration of only 0.17 mg/mL, extract of the seed cv. Malling Jewel effected a decrease in the frequency of MN of 60% compared with control cell cultures. PRACTICAL APPLICATION: Our results provide evidence of protective effects of currant seed extracts and isolated pure compounds on cytogenetic damages in human lymphocytes. Thus, currant seed extracts could exert beneficial effects in quite a few diseases, for many of the biological actions have been attributed to their antioxidant properties. PMID- 22670590 TI - Treatment of vibriosis in European sea bass larvae, Dicentrarchus labrax L., with oxolinic acid administered by bath or through medicated nauplii of Artemia franciscana (Kellogg): efficacy and residual kinetics. AB - European sea bass larvae were challenged by bath with Listonella anguillarum strain 332A, 2.5*10(7) CFUmL(-1) for 1h. Fish either received no treatment or oral treatment with Artemia franciscana (Kellog) nauplii enriched with oxolinic acid, or bath treatments with oxolinic acid. Medication commenced 1day following challenge and was performed on days 1, 3 and 5 post-challenge at a dosage of 20mgL(-1) for 2h for bath treatments, while two doses each of 750 nauplii per fish were administered daily for five consecutive days in oral treatments. Cumulative mortality reached 96% for the unmedicated challenged group, 32% in the group receiving bath treatments and 17% in the group receiving medicated nauplii. Pharmacokinetic parameters of oxolinic acid were calculated in sea bass larvae, for both treatments. Steady-state concentrations of oxolinic acid of 48.0 and 75.2MUgg(-1) were achieved for bath treatment and oral treatment, respectively, while the elimination half-life was calculated to be 25.1h for bath treatment and 21.7h for oral treatment. PMID- 22670591 TI - Comparison of a shortened isosorbide dinitrate-potentiated head-up tilt testing with the conventional protocol: tolerance and diagnostic accuracy. AB - BACKGROUND: The head-up tilt test (HUT) is widely used to investigate unexplained syncope; however, in clinical practice, it is long and sometimes not well tolerated. OBJECTIVES: To compare the sensitivity, specificity, accuracy, and patients' tolerance of a conventional and shortened HUT. METHODS: Patients with a history of vasovagal syndrome (VVS) were randomized to a conventional HUT (group I) consisting of 20-minute passive tilt followed by 25 minutes after administration of sublingual isosorbide dinitrate (ISDN), or a shortened HUT (group II) where ISDN was given immediately after tilt and observed for 25 minutes. The control group consisted of age- and gender-matched subjects without VVS symptoms. A specific questionnaire to evaluate tolerance was applied. RESULTS: Sixty patients (29 +/- 10 years, 82% female) were included. In group I, 22/30 patients had a positive HUT compared to 21/30 in group II (73% vs 70%, P = 0.77). There was also no difference in the accuracy between the two protocols (63% vs 73%, P = 0.24). The time to positivity was shorter in group II (13.2 minutes vs 30 minutes, P < 0.001). Within the control group (n = 60), the frequency of false-positives was 47% and 23% for the conventional and shortened HUT, respectively (P = 0.058). After conventional HUT, 65.2% subjects reported that the test was too long compared to 25% subjects after the shortened HUT (P = 0.002). CONCLUSION: In this study, the HUT without passive phase was not inferior to the conventional HUT regarding sensitivity, specificity, and accuracy. Furthermore, the shortened ISDN-potentiated protocol allowed faster diagnosis and was better tolerated. PMID- 22670592 TI - QSAR, docking and ADMET studies of artemisinin derivatives for antimalarial activity targeting plasmepsin II, a hemoglobin-degrading enzyme from P. falciparum. AB - This work presents the development of quantitative structure activity relationship (QSAR) model to predict the antimalarial activity of artemisinin derivatives. The structures of the molecules are represented by chemical descriptors that encode topological, geometric, and electronic structure features. Screening through QSAR model suggested that compounds A24, A24a, A53, A54, A62 and A64 possess significant antimalarial activity. Linear model is developed by the multiple linear regression method to link structures to their reported antimalarial activity. The correlation in terms of regression coefficient (r(2)) was 0.90 and prediction accuracy of model in terms of cross validation regression coefficient (rCV(2)) was 0.82. This study indicates that chemical properties viz., atom count (all atoms), connectivity index (order 1, standard), ring count (all rings), shape index (basic kappa, order 2), and solvent accessibility surface area are well correlated with antimalarial activity. The docking study showed high binding affinity of predicted active compounds against antimalarial target Plasmepsins (Plm-II). Further studies for oral bioavailability, ADMET and toxicity risk assessment suggest that compound A24, A24a, A53, A54, A62 and A64 exhibits marked antimalarial activity comparable to standard antimalarial drugs. Later one of the predicted active compound A64 was chemically synthesized, structure elucidated by NMR and in vivo tested in multidrug resistant strain of Plasmodium yoelii nigeriensis infected mice. The experimental results obtained agreed well with the predicted values. PMID- 22670593 TI - Lost productivity in four European countries among patients with rheumatic disorders: are absenteeism and presenteeism transferable? AB - BACKGROUND: When national pharmacoeconomic guidelines are compared, different recommendations are identified on how to identify, measure and value lost productivity, leading to difficulties when comparing lost productivity estimates across countries. From a transferability point of view, the question arises of whether differences between countries regarding lost productivity are the result of using different calculation methods (methodological differences) or of other between-country differences. When lost productivity data differ significantly across countries, the transferability of lost productivity data across countries is hindered. OBJECTIVE: The objective of this study was to investigate whether country of residence has a significant influence on the quantity of lost productivity among patients with rheumatic disorders. Confounding factors that might differ between countries were corrected for, while the methodology used to identify and measure lost productivity was kept the same. METHODS: This question was investigated by means of an online questionnaire filled out by 200 respondents with a rheumatic disorder per country in four European countries, namely the Netherlands, the UK, Germany and France. In addition to those regarding lost productivity, the questionnaire contained questions about patient characteristics, disability insurance, disease characteristics, quality of life and job characteristics as these variables are expected to influence lost productivity in terms of absenteeism and presenteeism. The data were analysed by regression analyses, in which different components - being absent in last 3 months, number of days absent and presenteeism - of lost productivity were the main outcome measures and other variables, such as gender, impact of disease, shift work, job control, partial disability and overall general health, were corrected for. RESULTS: The results showed that country sometimes has a significant influence on lost productivity and that other variables such as, for example, age, disease severity, number of contract hours, decision latitude, experienced health (as reported on the visual analogue scale) and partial disability, also influence lost productivity. A significant influence of country of residence was found on the variables 'being absent in the last three months', 'number of days absent' and 'quality of work on the last working day'. However, country did not influence 'quantity of work on the last working day' and 'overall presenteeism on the last working day'. CONCLUSION: It can be concluded that country has a significant influence on lost productivity among patients with rheumatic disorders, when corrected for other variables that have an influence on absenteeism and presenteeism. Transferring lost productivity data across countries without adaptation is hindered by the significant differences between countries in this patient group. As a result, transferring lost productivity data, being either monetary values or volumes of productivity losses, between countries can give wrong estimations of the cost effectiveness of treatments. PMID- 22670594 TI - Antinuclear antibodies in rheumatic disease: a proposal for a function-based classification. AB - Antinuclear antibodies (ANAs) are a diverse group of autoantibodies that bind macromolecular components of the cell nucleus. While some ANAs occur in normal individuals, others are expressed almost exclusively in patients with rheumatic disease and serve as markers for diagnosis and prognosis. Despite the clinical associations of ANAs, the relationship of these antibodies to specific disease manifestations is often unknown because the target antigens are intracellular molecules that are ubiquitously expressed. In systemic lupus erythematosus, the role of ANAs in disease manifestations is better understood, especially for antibodies to DNA and related nucleosomal antigens. These antibodies can promote nephritis by the formation of immune complexes that are deposited in the kidney. In addition, anti-DNA, along with antibodies to RNA-binding proteins such as anti Sm, can induce non-specific immune abnormalities based on the induction of type interferon 1 by plasmacytoid dendritic cells. Despite ANA expression in rheumatic disease, studies in animal models of inflammation and tissue injury indicate that antibodies to certain nuclear molecules such as HMGB1 have protective effects. Together, these considerations suggest a function-based classification of ANAs based on their expression in normal and autoimmune individuals as well as their capacity to induce or attenuate immunological disturbances. This classification provides a framework to elucidate the serological features of rheumatic disease and the often uncertain relationship between ANA expression and disease manifestations. PMID- 22670595 TI - Photon-manipulated drug release from a mesoporous nanocontainer controlled by azobenzene-modified nucleic acid. AB - Herein a photon-manipulated mesoporous release system was constructed based on azobenzene-modified nucleic acids. In this system, the azobenzene-incorporated DNA double strands were immobilized at the pore mouth of mesoporous silica nanoparticles. The photoisomerization of azobenzene induced dehybridization/hybridization switch of complementary DNA, causing uncapping/capping of pore gates of mesoporous silica. This nanoplatform permits holding of guest molecules within the nanopores under visible light but releases them when light wavelength turns to the UV range. These DNA/mesoporous silica hybrid nanostructures were exploited as carriers for the cancer cell chemotherapy drug doxorubicin (DOX) due to its stimuli-responsive property as well as good biocompatibility via MTT assay. It is found that the drug release behavior is light-wavelength-sensitive. Switching of the light from visible to the UV range uncapped the pores, causing the release of DOX from the mesoporous silica nanospheres and an obvious cytotoxic effect on cancer cells. We envision that this photocontrolled drug release system could find potential applications in cancer therapy. PMID- 22670596 TI - What is it about headache? PMID- 22670598 TI - The role of glucocorticoids in sodium retention in cirrhotic patients: a double blind, randomized, crossover study. AB - OBJECTIVE: Cirrhotic patients have an increased ratio of urinary cortisol to cortisone metabolites, indicating decreased renal 11-beta-hydroxysteroid dehydrogenase type-2 activity. This suggests that cortisol--by activation of the mineralocorticoid receptor--may contribute to the abnormal sodium retention evident in cirrhosis. The aim was to elucidate the role of glucocorticoids in sodium retention in decompensated cirrhotic patients. METHODS: A randomized, double-blind, placebo-controlled, crossover study was performed in nine patients with alcoholic cirrhosis of the liver. A washout interval of 14 days separated the two periods. After a basal period of 36 h, dexamethasone (0.5 mg every 6 h) or placebo was given for two days. Urine was collected for 12 h periods, and the concentrations of sodium, potassium, creatinine, cortisol and cortisol metabolites were determined. Blood samples for hemoglobin, glucose, sodium, potassium, creatinine, aldosterone and cortisol were obtained daily. RESULTS: Dexamethasone treatment decreased S-cortisol 92.3% (82.9-93.4%) (median and range) compared with that in the basal period. Natriuresis (dexamethasone- placebo) increased 55.1 (-26.4-168.7) mmol/day (median and range). No statistically significant differences (dexamethasone--placebo) were found in changes in body weight (0.00 (-0.45-2.20) kg/day), diuresis (0.56 (-0.35-1.43) L/day) or mean arterial pressure (8.33 (-16.0-41.3) mmHg) (median and range) in reference to the preceding 24 h basal period. CONCLUSION: These results indicate that endogenous glucocorticoids contribute to the sodium retention in patients with alcoholic cirrhosis of the liver. PMID- 22670599 TI - Patterns of condom use among students at historically Black colleges and universities: implications for HIV prevention efforts among college-age young adults. AB - Over 1.1 million Americans are living with human immunodeficiency virus (HIV), and African-American youth and young adults are disproportionately affected. Condoms are the most effective prevention tool, yet data regarding condom use patterns for African-American college youth are lacking. To inform and strengthen HIV prevention strategies with African-American college-age youth, we surveyed students attending 24 historically Black colleges and universities regarding condom use patterns. Students were administered anonymous questionnaires online to explore knowledge, attitudes, and practices related to condom use during last sexual intercourse (LSI). Among 824 sexually active respondents (51.8% female, median age 20 years, 90.6% heterosexuals), 526 (63.8%) reported condom use during LSI. Students who used condoms for disease prevention, whose mothers completed high school or had some college education or completed college were more likely to have used a condom during LSI. Spontaneity of sexual encounters, not feeling at risk of HIV, and partner-related perceptions were associated with condom non use during LSI (p<0.05). Over a third of our college youth sample did not use a condom during LSI and may benefit from increased condom education efforts. These efforts should highlight condoms' effectiveness in protection from HIV. Future HIV education and prevention strategies with similar groups of young adults should explore the implications of maternal education, clarify perceptions of HIV risk, and consider strategies that increase consistent condom use to interrupt sexual transmission of HIV. PMID- 22670600 TI - Health demand in primary care context: what do people think about physicians? AB - This research aims to explore the link between health demand and representation of medical function in a sample of 86 individuals (aged between 18 and 74) from Italy. A questionnaire has been administered for the analysis of cultural models (Carli & Paniccia 1999) in terms of affective symbolisations characterising physician-patient relationship. The questionnaire has been constructed according to a socio-constructivist methodology and allows to explore two specific emotional areas: (1) The view about medical profession and health care setting in general, (2) the experience referred to one's own general practitioner. Five clusters of subjects have been identified, thanks to multivariate statistic techniques (multiple correspondence analysis (MCA) and cluster analysis (CA). They show respectively: A deep concern for health and a paternalistic dynamics with physician (20.9% of the sample); a general distrust of the health service and a fatalistic view about health leading to avoid the use of visits (16.3%); a passive and dependent position in relation to physician seen as a skilled and powerful technician (20.9%); a little compliance with physician considered as a bureaucrat that must satisfy any request (20.9%); an active role in health management and a greater confidence in medical function for a better quality of life (20.9%). Results point out some differences by age, education and occupation. In particular, participants with university schooling (p < 0. 01) and professionals (p < 0. 05) show less motivation to use primary care services, while participants aged from 45 to 74 years (p < 0.05) and with elementary-middle schooling (p < 0.05) are more confident in medical function for health promotion. Findings suggest some indications on health demand and provide development lines for improving communication in primary care context. PMID- 22670597 TI - Endothelin-1 and the kidney--beyond BP. AB - Since its discovery over 20 years ago endothelin-1 (ET-1) has been implicated in a number of physiological and pathophysiological processes. Its role in the development and progression of chronic kidney disease (CKD) is well established and is an area of ongoing intense research. There are now available a number of ET receptor antagonists many of which have been used in trials with CKD patients and shown to reduce BP and proteinuria. However, ET-1 has a number of BP independent effects. Importantly, and in relation to the kidney, ET-1 has clear roles to play in cell proliferation, podocyte dysfunction, inflammation and fibrosis, and arguably, these actions of ET-1 may be more significant in the progression of CKD than its prohypertensive actions. This review will focus on the potential role of ET-1 in renal disease with an emphasis on its BP independent actions. PMID- 22670601 TI - Mini-review: spinocerebellar ataxias: an update of SCA genes. AB - Autosomal dominant spinocerebellar ataxias (SCAs) are a complex group of debilitating and neurodegenerative diseases that affect the cerebellum and its main connections and characterized by a generalized incoordination of gait, speech, and limb movements. In general, the onset of SCAs occurs during adult life and shows great clinical heterogeneity. Currently, the mutations responsible for different types of SCAs have been localized in different regions of the genome, and most of them were already mapped and cloned. Several pieces of evidence suggest that all these diseases share the same molecular mechanism and physiopathological processes. CAG trinucleotide expansion is a common mutational basis of several of these disorders. An expanded polyglutamine tract may become a toxic product when located within the coding region of the gene. The SCA genes, recent patents and the molecular aspects of these disorders are presented in this review. Our knowledge of the molecular mechanisms of SCAs is rapidly expanding, and the development of important studies is bringing hope for effective therapies. PMID- 22670602 TI - Advances in the management of malignant hemopathies: the role of statins. AB - Today, hematology is dependent on molecular biology for diagnosis, establishing the prognosis and treatment guidance in more and more diseases. One useful technique in this respect is the gene expression profiling, whose use is not yet a matter of routine. The discovery that the expression of LDL-receptor and cholesterol synthesis is increased in the cells of some leukemias and lymphomas and that some statins induced DNA damages and increased the level of reactive oxygen species, opens the possibility of using statins in the treatment of certain malignant hemopathies. Patents regarding their association with dipyridamole, retinoids, tipifarnib, cytostatics or chemotherapy programs contribute to increasing their effectiveness. Statins can increase the apoptosis of malignant cells and restore the chemosensitivity in patients with different malignant hemopathies. Techniques of molecular biology are useful for identifying patients who have indication for statins. The main adverse effects of statins are increased transaminase levels and myopathy. The last may be anticipated and treated today. PMID- 22670603 TI - Recent patents on high-throughput single nucleotide polymorphism (SNP) genotyping methods. AB - Single nucleotide polymorphisms (SNPs) are single-base inheritable variations in a given and defined genetic location that occur in at least 1% of the population. SNPs are useful markers for genetic association studies in disease susceptibility or adverse drug reactions, in evolutionary studies and forensic science. Given the potential impact of SNPs, the biotechnology industry has focused on the development of high-throughput methods for SNP genotyping. Many highthroughput SNP genotyping technologies are currently available and many others are being patented recently. Each offers a unique combination of scale, accuracy, throughput and cost. In this review, we described some of the most important recent SNP genotyping methods and also recent patents associated with it. PMID- 22670604 TI - Licensed DNA Vaccines against Infectious Hematopoietic Necrosis Virus (IHNV). AB - This article reviews some of the recent patents on DNA vaccines against fish viruses, in particular against the novirhabdovirus infectious hematopoitic necrosis virus (IHNV). Although very effective in protecting fish against IHNV, only one DNA vaccine has been approved to date for use in Canada. In Europe and in US, its commercialization is restricted due to safety concerns. PMID- 22670605 TI - Patents in the era of genomics: an overview. AB - The recent developments in biotechnology are the emerging science of "omics"- genomics, proteomics, transcriptomics and metabolomics. The state of the art sequencing technology has led to the deciphering of whole genome sequences of various microbes, plant, human and animals. The outcomes of genomics in the form of various genes, gene fragments, single nucleotide polymorphism, promoters and other regulatory sequences are a subject matter for patents based on its applications spanning agricultural, biomedical and industrial sectors. The patenting of genes and sequences is a debatable issue which has led to several controversies over recent years. With the accumulation of huge amount of sequences in various databases as a result of various genome sequencing projects worldwide, there is an immediate need for clarification of patenting genes and sequences. This review article gives an insight into patents based on development of genomics highlighting some of the patents based on deoxyribonucleic acid, genes, sequences and other related genetic material and gene technologies. Patents on single nucleotide polymorphism, stem cells, biomarkers for cancer diagnosis and treatment, microbial genes and plant genes are also discussed. PMID- 22670606 TI - Evaluation of Brazilian biotechnology patent activity from 1975 to 2010. AB - The analysis of patent activity is one methodology used for technological monitoring. In this paper, the activity of biotechnology-related patents in Brazil were analyzed through 30 International Patent Classification (IPC) codes published by the Organization for Economic Cooperation and Development (OECD). We developed a program to analyse the dynamics of the major patent applicants, countries and IPC codes extracted from the Brazilian Patent Office (INPI) database. We also identified Brazilian patent applicants who tried to expand protection abroad via the Patent Cooperation Treaty (PCT). We had access to all patents published online at the INPI from 1975 to July 2010, including 9,791 biotechnology patent applications in Brazil, and 163 PCTs published online at World Intellectual Property Organization (WIPO) from 1997 to December 2010. To our knowledge, there are no other online reports of biotechnology patents previous to the years analyzed here. Most of the biotechnology patents filed in the INPI (10.9%) concerned measuring or testing processes involving nucleic acids. The second and third places belonged to patents involving agro technologies (recombinant DNA technology for plant cells and new flowering plants, i.e. angiosperms, or processes for obtaining them, and reproduction of flowering plants by tissue culture techniques). The majority of patents (87.2%) were filed by nonresidents, with USA being responsible for 51.7% of all biotechnology patents deposited in Brazil. Analyzing the resident applicants per region, we found a hub in the southeast region of Brazil. Among the resident applicants for biotechnology patents filed in the INPI, 43.5% were from Sao Paulo, 18.3% were from Rio de Janeiro, and 9.7% were from Minas Gerais. Pfizer, Novartis, and Sanofi were the largest applicants in Brazil, with 339, 288, and 245 biotechnology patents filed, respectively. For residents, the largest applicant was the governmental institution FIOCRUZ (Oswaldo Cruz Foundation), which filed 69 biotechnology patents within the period analyzed. The first biotechnology patent applications via PCT were submitted by Brazilians in 1997, with 3 from UFMG (university), 2 from individuals, and 1 from EMBRAPA (research institute). PMID- 22670607 TI - Breaking the bond: recent patents on bacterial adhesins. AB - Adhesins need to be exposed on the surface of pathogenic bacteria to properly interact with host tissues and allow establishment of the infection. This fact implies that, in theory, one could manage or avoid infection by controlling adhesins' function, and also by indirectly detecting bacteria through their surface-exposed adhesins. Besides, binding of anti-adhesin immunoglobulins on the bacterial surface tend to promote the opsonization of the pathogen. Therefore, bacterial adhesins represent a great target to develop new biopharmaceuticals, which may become commercially and medically important products. In this review, we will summarize the biological importance of bacterial adhesins, and also discuss some recent patents related to these molecules, as well as their use and possible new future developments in this area. PMID- 22670608 TI - Advances in lentiviral vectors: a patent review. AB - Lentiviral vectors are at the forefront of gene delivery systems for research and clinical applications. These vectors have the ability to efficiently transduce nondividing and dividing cells, to insert large genetic segment in the host chromatin, and to sustain stable long-term transgene expression. Most of lentiviral vectors systems in use are derived from HIV-1. Numerous modifications in the basic HIV structure have been made to ensure safety and to promote efficiency to vectors. Lentiviral vectors can be pseudotyped with distinct viral envelopes that influence vector tropism and transduction efficiency. Moreover, these vectors can be used to reprogram cells and generate induced pluripotent stem cells. This review aims to show the patents that resulted in improved safety and efficacy of lentiviral vector with important implications for clinical trials. PMID- 22670609 TI - Recent patents in siRNA delivery employing nanoparticles as delivery vectors. AB - Small interfering RNAs (siRNAs) are rapidly emerging as new therapeutic tools for the treatment of some of the deadly diseases such as cancer. However, poor cellular uptake and instability in physiological milieu limit its therapeutic potential, hence there arises a need of a delivery system which can efficiently and repeatedly deliver siRNA to the target cells. Nanoparticles have shown immense potential as suitable delivery vectors with enhanced efficacy and biocompatibility. These delivery vectors are usually few nanometers in size, which not only protects siRNA against enzymatic degradation but also leads to tissue and cellular targeting. Nanoparticles prepared from various cationic polymers like polyethylenimine, and chitosan have been largely exploited as they bear several advantages such as, ease of manipulation, high stability, low cost and high payload. This review summarizes some of the recent patents on siRNA delivery employing polymer or lipid-based nano-vectors for therapeutic applications. PMID- 22670610 TI - Polymers for gene delivery: current status and future perspectives. AB - Gene therapy is a hope for curing many diseases and pathological conditions which are relatively difficult to treat. However lack of proper gene delivery vehicle is the main limiting step in this direction. Though viral vectors still lead as the major vehicle used in gene therapy clinical trials, their immunogenicity and low capacity restrict their wide use. Hence there is a need for developing non viral vectors which can really be used for clinical applications. Polymers are a versatile group of molecules which can be modified and designed or engineered according to the end needs of the applications. The objective of this review is to summarize the recent advances in the development of polymeric vectors for gene delivery applications reported in patents and scientific journals. PMID- 22670611 TI - Gene delivery by functional inorganic nanocarriers. AB - Gene delivery into cells to elicit cellular response has received a great attention recently. Viruses, lipids, peptides, cationic polymers and certain inorganic nanomaterials have been reported as gene delivery vectors. In this review, we focus on the recent literature on gene delivery using inorganic nanoparticles. This emerging field of study is concisely summarized and illustrated by selected examples and recent patents. New approaches and directions towards the practical use of multifunctional nanocarriers are highlighted. PMID- 22670612 TI - Beyond the blot: cutting edge tools for genomics, proteomics and metabolomics analyses and previous successes. AB - The skin has an amazing array of complex interacting biological processes. Recent advances in investigational techniques now allow evaluation of these processes at the level of the gene, protein and metabolite. Sometimes collectively known as the omics, these fields of inquiry, known as genomics, proteomics and metabolomics, respectively, are yielding new and important insights into skin structure and processes, its responses to injury and age, and the mechanisms by which new interventions and compounds may work to improve the health and integrity of this crucial organ. PMID- 22670613 TI - Skin differences based on age and chronicity of ultraviolet exposure: results from a gene expression profiling study. AB - BACKGROUND: Skin ageing represents an inevitable physiological consequence of getting older but the impact on personal health and wellbeing can be significant, and therefore considerable efforts have been made to understand the biology and pathophysiology of skin ageing to try to identify new targets that might offer therapeutic intervention and prevention. OBJECTIVES: This study was designed to identify differences at the gene expression level between young and old, sun exposed and sun-protected skin. METHODS: We generated transcriptomic data from young and old skin from sun-exposed and sun-protected sites (10 samples of each) using HG-U133 Plus 2.0 Affymetrix GeneChips. The data were analysed using hierarchical clustering, theme analysis and interaction mapping to identify regulated pathways, processes and potential targets for therapy. RESULTS: With 54,613 probe sets on the GeneChip, 2731 significant differences would be expected by chance (at P = 0.05), but we noted that 13,640 probe sets were significantly different comparing young arm skin vs. older arm skin (photoageing), and 7215 probe sets were significant for the young buttock vs. older buttock comparison (intrinsic ageing). In both types of ageing there was reduced expression of many genes implicated in lipid biosynthesis and epidermal differentiation with functional relevance to skin barrier integrity and maintenance. Increased expression of genes contributing to oxidative stress and decreased expression of antioxidant defences were also common to both types of ageing. Differences between intrinsic ageing and photoageing were mainly noted in extracellular matrix gene expression with reduced expression of interstitial collagen genes in intrinsic ageing and increased expression of elastic tissue genes in photoageing. CONCLUSIONS: Collectively, the data identified new biomarkers of aged skin, particularly involving abnormalities of proteases, matrix proteins and inflammation. These findings offer the prospect of new and more specific targets for therapeutic development based on an improved understanding of the biology of skin ageing. PMID- 22670614 TI - Application of genomics to breakthroughs in the cosmetic treatment of skin ageing and discoloration. AB - The use of global gene expression profiling, also known as transcriptomics or genomics, provides a means to identify key pathways affected in ageing skin that can be improved with appropriate cosmetic compounds. Aspects of skin ageing that can be addressed include matrix production, barrier, lipid synthesis, antioxidant capacity and hyperpigmentation. Gene expression profiling together with in vitro human skin cell cultures for compound screening and verification have led to the identification of cosmetic compounds and an understanding of the biological effects of compounds such as niacinamide, Pal-KTTKS, hexamidine, retinyl propionate and sodium dehydroacetate. In addition, understanding of the decreased antioxidant capacity of aged skin has led to the identification of new antiageing ingredients, olive-derived fatty acid ethoxylates, which have been shown to restore antioxidant enzymes in skin keratinocytes and fibroblasts. Gene expression profiling of age spots has also provided an understanding of the role of undecylenoyl phenylalanine in reducing melanin production by an adrenergic receptor mechanism in melanocytes. The use of these compounds in cosmetic formulations for skin care can aid improvements in the appearance of aged skin, including the improved appearance of fine lines, wrinkles and age spots. PMID- 22670615 TI - A novel monilethrix mutation in coil 2A of KRT86 causing autosomal dominant monilethrix with incomplete penetrance. AB - BACKGROUND: Monilethrix is a genetic hair shaft disorder that causes a dystrophic alopecia. Mutations causing autosomal dominant monilethrix have been found in the helix initiation and helix termination motifs of the type II hair keratins KRT81, KRT83 and KRT86. Mutations in DSG4 are linked to recessive transmission. OBJECTIVES: We investigated a large Tasmanian family demonstrating autosomal dominant monilethrix with incomplete penetrance in order to identify the responsible genetic mutation. As only some affected hairs were moniliform, analysis was undertaken to demonstrate a deficit in the tensile strength of nonmoniliform hairs. METHODS: One hundred and twenty family members were examined. Light microscopy of hair samples was used to support clinical diagnoses. Linkage and gene sequencing studies were then undertaken. Nonbeaded fibres were analysed using the Single Fibre Analyser 3 (SIFAN 3). RESULTS: We identified a novel A280V (c.839C > T substitution) mutation in the coil 2A region of KRT86. This is the first mutation located in a region other than the helix initiation or termination motifs. The A280V mutation was identified in both affected and clinically unaffected family members. Nonmoniliform hairs demonstrated reduced elasticity among both affected and unaffected individuals carrying the A280V mutation. CONCLUSIONS: This is the first mutation located in a region other than the helix initiation or termination motifs, thus expanding the spectrum of mutations and highlighting the importance of molecular diagnosis in monilethrix. PMID- 22670616 TI - The proteomic profile of hair damage. AB - BACKGROUND: Monilethrix is a congenital hair shaft disorder with associated fragility. Many of the changes seen in monilethrix hair on light microscopy and scanning electron microscopy are also seen in hair weathering and cosmetic damage to hair. OBJECTIVES: We used monilethrix as a model to investigate the relationship between hair protein structure and hair strength and resistance to cosmetic insult. METHODS: We applied proteomic techniques to identify novel peptide damage markers for chemical oxidative damage to hair. RESULTS: The findings suggest that specific sites in the protein structure of hair are targeted during oxidative damage from bleaching, a unique insight into how chemical damage compromises the structural integrity of the hair shaft at the molecular level. CONCLUSIONS: Applying proteomics to the study of congenital and acquired hair shaft disorders can deliver new insights into hair damage and novel strategies to strengthen hair. PMID- 22670617 TI - Dandruff/seborrhoeic dermatitis is characterized by an inflammatory genomic signature and possible immune dysfunction: transcriptional analysis of the condition and treatment effects of zinc pyrithione. AB - BACKGROUND: Dandruff/seborrhoeic dermatitis is a common scalp condition that is characterized by flakes, pruritus and sometimes mild erythema. These symptoms reflect tissue level events that are poorly understood at the molecular level. OBJECTIVES: The purpose of this work was: (i) to compare gene expression profiles in subjects with dandruff vs. those of subjects without dandruff to determine the key physiological disruptions manifest in the condition; and (ii) to determine the effect on this profile of treatment with a shampoo containing potentiated zinc pyrithione (ZPT). METHODS: In study 1, scalp biopsies were taken from 16 normal subjects and from involved and uninvolved sites in 15 subjects with dandruff. In study 2, 30 subjects with dandruff were treated for 3 weeks with a commercial ZPT shampoo (n = 15) or a vehicle (n = 15), and scalp lesional biopsies were collected at baseline and end of study for transcriptomic analysis. RNA was extracted from all biopsies and Affymetrix gene chips were used to analyse transcriptomic profiles, followed by bioinformatic analysis. RESULTS: Analysis of study 1 biopsies revealed more than 7000 individual probes differentially regulated in dandruff lesional skin relative to normal. Enriched Gene Ontology categories included: lipid metabolism, immune response, response to stimulus, apoptosis, cell proliferation, and epidermal development. The most striking feature of lesional skin relative to normal was the reciprocal expression of induced inflammatory genes and repressed lipid metabolism genes. Induced inflammatory genes were also enriched in dandruff uninvolved skin, suggesting the existence of predisposing factors associated with inflammation. Many genes increased in lesional skin were increased at the level of protein in stratum corneum samples (e.g. IL-1RA, S100A8, S100A9, S100A11, IL-8). Under conditions known to improve overall scalp condition, the ZPT shampoo treatment in study 2 produced a transcriptomic profile resembling that of normal scalp skin. CONCLUSIONS: These data provide novel insights into the nature of dandruff and the therapeutic action of potentiated ZPT-containing shampoo, and provide a basis to explore many new mechanistic questions related to these topics. PMID- 22670618 TI - Comparison of the impact of environmental stress on male and female skin. AB - Past research on understanding gender differences of skin biology and its response to environmental insults has focused on morphological and gross physiological comparisons. In general it has been found that male skin has a greater susceptibility to being negatively impacted by environmental stressors, in particular ultraviolet radiation. These noted differences in response to environmental insults are probably due to a combination of underlying biologically based differences and variable sun-protection and skin-care product usage between genders. Overall, published data support the hypothesis that male facial skin undergoes significant challenges from environmental insults that lead to a more damaged condition compared with female skin. These changes occur both from acute insults and from the impact of cumulative chronic exposure. Appropriate sun protection should be viewed as an important step in male skin care and grooming habits. PMID- 22670619 TI - A new era in skin care: the omics revolution. PMID- 22670620 TI - Activity of caprylic acid, carvacrol, epsilon-polylysine and their combinations against Salmonella in not-ready-to-eat surface-browned, frozen, breaded chicken products. AB - Caprylic acid (CAA), carvacrol (CAR), epsilon-polylysine (POL), and their combinations were evaluated for reduction of Salmonella contamination in not ready-to-eat surface-browned, frozen, breaded chicken products. Fresh chicken breast meat pieces (5 * 5 * 5 cm) were inoculated with Salmonella (7-strain mixture; 4-5 log CFU/g) and mixed with distilled water (control) or with CAA, CAR, and POL as single or combination treatments of 2 or 3 ingredients. Sodium chloride (1.2%) and sodium tripolyphosphate (0.3%) were added to all formulations, followed by grinding of the mixtures and forming into 9 * 5 * 3 cm portions. Sample surfaces were brushed with egg whites, coated with breadcrumbs, surface-browned in an oven (208 degrees C, 15 min), packaged, and stored at -20 degrees C (7 d). Total reductions of inoculated Salmonella in untreated (control) surface-browned, breaded products after frozen storage were 0.8 to 1.4 log CFU/g. In comparison, single treatments of CAA (0.25% to 1.0%), CAR (0.3% to 0.5%), and POL (0.125% to 1.0%) reduced counts by 2.9 to at least 4.5, 3.4 to at least 4.4, and 1.4 to 2.3 log CFU/g, respectively, depending on concentration. Pathogen counts of products treated with 2- or 3-ingredient combination treatments (0.03125% to 0.25% CAA, 0.0375% to 0.3% CAR, and/or 0.5% POL) were 0.4 to at least 3.3 log CFU/g lower (depending on treatment) than those of the untreated controls. The antimicrobial activity of 2-ingredient combinations comprised of 0.125% CAA, 0.15% CAR, or 0.5% POL was enhanced (P < 0.05) when applied as a 3 ingredient combination (that is, 0.125% CAA + 0.15% CAR + 0.5% POL). These data may be useful for the selection of antimicrobial treatments to reduce Salmonella contamination in not-ready-to-eat processed chicken products. PRACTICAL APPLICATION: Findings from the study may be useful for the selection of suitable antimicrobials, concentrations, and combinations to reduce Salmonella contamination in not-ready-to-eat surface-browned, frozen, breaded chicken products. PMID- 22670621 TI - Long-term compliance with follow-up after treatment for cervical intra-epithelial neoplasia. AB - OBJECTIVE: To assess the level of compliance with follow-up over time after treatment for preinvasive and Stage Ia1 lesions of the cervix. To compare the average interval between visits with the interval prescribed by protocol and to evaluate the use of this difference as a measure of compliance. DESIGN: Retrospective observational study. Setting. London university hospital. POPULATION: Women who received treatment for preinvasive (CINI-III, AIS) or Stage Ia1 cervical lesions. METHODS: Attendance data were obtained from hospital-based colposcopy and community-based databases. MAIN OUTCOME MEASURES: The average interval between the appointments attended by each woman was compared with the planned interval between visits. The time that elapsed since the previous appointment attended was calculated for each visit and correlated with the time since treatment. RESULTS: 1013 women attended 4128 follow-up visits in the colposcopy clinic and in the community. Twenty-two (2.2%) women never attended any post-treatment appointment and 209 (21.0%) of the 991 women who attended at least once, did so on average more than 12 months later than specified by the follow-up protocol. There was a highly significant correlation between the interval since the previous appointment and the time since treatment (Kendall's tau b = 0.529614, two-sided p < 0.0001), showing that compliance deteriorates with increasing time since treatment. CONCLUSIONS: Comparing the average interval between attendances with the planned interval prescribed by protocol is a sensitive measure of compliance. Compliance with follow-up deteriorates significantly with time since treatment. This decline in compliance may contribute to the increased risk of invasive disease after treatment. PMID- 22670622 TI - Identification of single nucleotide polymorphisms in the bovine follicle stimulating hormone receptor and effects of genotypes on superovulatory response traits. AB - In dairy cows, there is evidence that failure to respond to superovulation protocols is a heritable trait. In women, genotyping for the p.N680S single nucleotide polymorphism (SNP) in the follicle-stimulating hormone receptor (FSHR) gene may help identify poor responders before ovarian stimulation is initiated. Our objectives were to identify SNPs in the coding region of the bovine FSHR gene and to investigate the effect of FSHR genotypes on superovulatory response in Holstein cattle. Sequencing of FSHR exons 1-10 revealed seven SNPs. Three were non-synonymous mutations (c.337C>G, c.871A>G and c.1973C>G). SNP c.337C>G encodes for a proline-to-alanine (p.Pro113Ala) amino acid replacement in the extracellular ligand-binding domain of the receptor. PCR-RFLP analyses showed that homozygous GG Holstein cows present a higher percentage of viable embryos, whereas GG and CG animals have less unfertilised oocytes. SNP c.871A>G results in an isoleucine-to-valine (p.Ile291Val) modification, and homozygous AA animals present lower embryo yield after superovulatory treatments. SNP c.1973C>G corresponds to a threonine-to-serine (p.The658Ser) modification in the intracellular carboxyl-terminal domain of the FSHR protein, and homozygous GG Holstein cows were associated with a lower embryo yield and a higher percentage of unfertilised oocytes. Our results suggest that specific alleles of the bovine FSHR gene are associated with variations in embryo yield and in the number of unfertilised oocytes. PMID- 22670623 TI - Quantification of allergenic bovine milk alpha(S1)-casein in baked goods using an intact 15N-labeled protein internal standard. AB - Intact bovine 15N-alpha(S1)-casein was used as an internal standard in a selected reaction monitoring (SRM) assay for milk protein in baked food samples containing fats, sugar, and gums. Effects on SRM results of sample matrix composition in two biscuit recipes containing nonfat dry milk (NFDM) were studied, including samples from a milk allergen ELISA proficiency trial. Following extraction of defatted samples with carbohydrate-degrading enzymes and acid precipitation of casein, the SRM assay exhibited an LOQ of <3 ppm NFDM with 60-80% recovery. NFDM levels measured by the SRM assay were 1.7-2.5 times greater than median levels determined by ELISA. Differences were observed in the alpha(S1)-casein interpeptide SRM ion abundance profile between recipes and after baking. 15N alpha(S1)-Casein increases SRM analysis accuracy by correcting for extraction recovery but does not eliminate underestimation of allergen concentrations due to baking-related milk protein transformation (modifications). PMID- 22670624 TI - Molecular Interaction Between Smurfl WW2 Domain and PPXY Motifs of Smadl, Smad5, and Smad6-Modeling and Analysis. AB - Abstract The ubiquitin-proteasome proteolytic pathway is essential for various important biological processes including cell cycle progression, gene transcription, and signal transduction. One of the important regulatory mechanisms by which the bone-inducing activity of the bone morphogenetic protein (BMP) signaling is modulated involves ubiquitin-mediated proteasomal degradation. The BMP induced receptor signal is transmitted intracellularly by phosphorylation of Smad proteins by the activated receptor I. The phosphorylated Smads 1, 5, and 8 (R-Smads) oligomerize with the co-Smad (Smad4). The complex, thus, formed translocates to the nucleus and interacts with other cofactors to regulate the expression of downstream target genes. R-Smads contain PPXY motif in the linker region that interacts with Smad ubiquitin regulatory factor 1 (Smurf1), an E3 ubiquitin ligase that catalyzes ubiquitination of target proteins for proteasomal degradation. Smurf1 contains a HECT domain, a C2 domain, and 2 WW domains (WW1, WW2). The PPXY motif in target proteins and its interaction with Smurf1 may form the basis for regulation of steady-state levels of Smads in controlling BMP responsiveness of cells. Here, we present a homology-based model of the Smurf1 WW2 domain and the target octa-peptides containing PPXY motif of Smurf1- interacting Smads. We carried out docking of Smurf1 WW2 domain with the PPXY motifs of Smadl, Smad5, and Smad6 and identified the key amino acid residues involved in interaction. Furthermore, we present experimental evidence that WW2 domain of Smurf1 does indeed interact with the Smad proteins and that the deletion of WW2 domain of Smurf1 results in loss of its binding to Smads using the purified recombinant proteins. Finally, we also present data confirming that the deletion of WW2 domain in Smurf1 abolishes its ubiquitination activity on Smad1 in an in vitro ubiquitination assay. It shows that the interaction between the WW domain and Smad PPXY motif is a key step in Smurf1-mediated ubiquitination of its natural targets such as Smad1, Smad5, and Smad6. This work facilitates further strategies to unravel the biological function of such interactions and help in designing effective mimetic compounds that either mimic or disrupt the specific interaction. PMID- 22670625 TI - Efficient in vivo gene transfer by intraperitoneal injection of plasmid DNA and calcium carbonate microflowers in mice. AB - Gene transfer to intraperitoneal organs is thought to be a promising approach to treat such conditions as peritoneal fibrosis and peritoneal dissemination of cancers. We previously discovered that simple instillation of naked plasmid DNA (pDNA) onto intraperitoneal organs such as the liver and stomach could effectively transfer foreign genes in mice. In this study, we developed a novel nonviral method to enhance transfection efficiency of naked pDNA to intraperitoneal organs using a calcium carbonate suspension containing pDNA. Using commercially available calcium carbonate, we successfully transfected pDNA to the stomach. Handling of commercially available calcium carbonate, however, was troublesome owing to rapid precipitation and caking. To obtain slowly settling particles of calcium carbonate, we tried to synthesize novel versions of such particles and succeeded in creating flower-shaped particles, named calcium carbonate microflowers. Sedimentation of calcium carbonate microflowers was sufficiently slow for in vivo experiments. Moreover, the transfection efficiency of the suspension of calcium carbonate microflowers to the stomach was more effective than that of commercially available calcium carbonate, especially at low concentrations. Intraperitoneal injection of the suspension of calcium carbonate microflowers containing pDNA greatly enhanced naked pDNA transfer to whole intraperitoneal organs in mice. Furthermore, lactate dehydrogenase activities in intraperitoneal fluid and plasma were not raised by the suspension of calcium carbonate microflowers. PMID- 22670626 TI - Arabidopsis GT34 family contains five xyloglucan alpha-1,6-xylosyltransferases. AB - The Arabidopsis genome includes seven family 34 glycosyltransferase (GT34) encoding genes. XXT1 and XXT2 have previously been shown to encode XyG alpha-1,6 xylosyltransferases, while knockout mutants of a third, XXT5, exhibit decreased XyG content, suggesting a similar activity. Here, we extend the study to the rest of the Arabidopsis GT34 genes in terms of biochemical activity and their roles in XyG biosynthesis. The enzyme activity of XXTs was investigated using recombinant protein expressed in E. coli. XyG analysis of single and double T-DNA insertion knockouts, together with overexpression of GT34s in selected mutant lines, provided detailed function of each gene. We reveal the activity of the third member of the GT34 gene family (XXT4) that exhibits xylosyltransferase activity. Double mutants for either xxt2 or xxt5 had a large impact on XyG content, structure and size distribution. Overexpression of the remaining member, XXT3, was able to restore XyG epitopes in xxt2, xxt5 and xxt2 xxt5 double knockouts, suggesting that it also encodes a protein with XXT activity. Our work demonstrates that five of the seven Arabidopsis GT34 genes encode XXT enzymes. PMID- 22670627 TI - Electrophysiology studies in patients undergoing ICD implantation: findings from the NCDR(r). AB - BACKGROUND: Electrophysiology studies (EPS) have historically played a role in sudden death risk stratification. More recent studies point to the left ventricular ejection fraction (EF) as a guide to implantable cardioverter defibrillators (ICD) implantation. The extent of EPS use in patients undergoing ICD implantation in the current era remains unknown. METHODS: Patients undergoing de novo ICD implantation in the ICD Registry between September 2006 and March 2009 who also underwent EPS within 30 days before implant were compared to the remaining cohort to identify clinical characteristics that correlated with EPS performance. Multivariate models were generated using hierarchical logistic regression analysis. RESULTS: EPS were performed in 33,786 of 275,273 patients. Those undergoing EPS were more likely to have had a history of syncope, family history of sudden death, lack of congestive heart failure, narrower QRS intervals, and higher EF. Overall, 63.9% of EPS were performed in patients receiving primary prevention ICDs. Ventricular tachyarrhythmias were induced in 46.1% of primary prevention and 54.2% of secondary prevention ICD recipients. Monomorphic ventricular tachycardia was the most common type of arrhythmia induced in both groups. Complication rates were not higher in those undergoing EPS. CONCLUSIONS: EPS were performed predominantly in patients with borderline or less well-defined risk factors for sudden death. Ventricular arrhythmias induced from EPS were not uncommon and may help identify individuals at higher risk for future ICD therapies. Efforts to better define the role of EPS in patients undergoing ICD implantation should be considered. PMID- 22670628 TI - Interaction between endogenous and exogenous orienting in crossmodal attention. AB - Using a cue-target paradigm, we investigated the interaction between endogenous and exogenous orienting in cross-modal attention. A peripheral (exogenous) cue was presented after a central (endogenous) cue with a variable time interval. The endogenous and exogenous cues were presented in one sensory modality (auditory in Experiment 1 and visual in Experiment 2) whereas the target was presented in another modality. Both experiments showed a significant endogenous cuing effect (longer reaction times in the invalid condition than in the valid condition). However, exogenous cuing produced a facilitatory effect in both experiments in response to the target when endogenous cuing was valid, but it elicited a facilitatory effect in Experiment 1 and an inhibitory effect in Experiment 2 when endogenous cuing was invalid. These findings indicate that endogenous and exogenous cuing can co-operate in orienting attention to the crossmodal target. Moreover, the interaction between endogenous and exogenous orienting of attention is modulated by the modality between the cue and the target. PMID- 22670629 TI - Plasma cell myeloma associated with Epstein-Barr virus infection in an 11-year old girl. AB - Multiple myeloma is extremely rare in children and represents fewer than 1% of all patients with myeloma. We report a case of multiple myeloma in an 11-year-old girl, who presented with a well-differentiated immunoglobulin A/kappa plasmacytoma at the base of the skull at 9 years of age; at that time, the bone marrow biopsy was negative. Two years later, the patient experienced generalized bone pain with multiple lytic bone lesions that affected the skull, long bones, ribs, and clavicle. The bone marrow biopsy showed a well-differentiated (Marschalko-type) multiple myeloma that was positive for CD138 and immunoglobulin A, with kappa light chain restriction. Interestingly, the Epstein-Barr virus (EBV) was detected by in situ hybridization for EBV-encoded RNA (EBER) in the majority of the neoplastic cells from both biopsy specimens. The patient responded favorably to treatment with dexamethasone, thalidomide, and zoledronic acid and is scheduled for bone marrow transplantation. PMID- 22670630 TI - Structural evolution in the isotropic channel of a water-nonionic surfactant system that has a disconnected lamellar phase: a 1H NMR self-diffusion study. AB - We showed in a previous study that a water-nonionic surfactant system, where the surfactant is a 9:1 mixture of tetraethylene glycol monodecyl ether (C(10)E(4)) and pentaethylene glycol monodecyl ether (C(10)E(5)), forms a disconnected lamellar (L(alpha)) phase. Thus, the isotropic phase spans the whole concentration range from the water-rich L(1) region to the surfactant-rich L(2) region of the phase diagram. The L(1) and L(2) regions are connected via an isotropic channel that separates the two regions of the L(alpha) phase. In this letter, we monitored the structural evolution of the isotropic phase along a path through this isotropic channel via (1)H NMR self-diffusion measurements. We used this technique because it enables us to distinguish between discrete and bicontinuous structures by comparing the relative self-diffusion coefficients (obstruction factors) D/D(0) of the solvents (i.e. of water and surfactant in the present case). We found that the obstruction factor of water decreases whereas the obstruction factor of the surfactant increases with increasing surfactant concentration and increasing temperature. This trend is interpreted as the transition from a water-continuous L(1) region, which contains discrete micelles, to a bicontinuous structure, which may extend to very high surfactant concentrations. Although there is good evidence of bicontinuity over a broad concentration range, there is no evidence of inverse micelles or any other microstructure at the highest concentration studied in the surfactant-rich L(2) phase. PMID- 22670631 TI - Sequential deletion of all the polyketide synthase and nonribosomal peptide synthetase biosynthetic gene clusters and a 900-kb subtelomeric sequence of the linear chromosome of Streptomyces coelicolor. AB - Streptomyces coelicolor, with its 8 667 507-bp linear chromosome, is the genetically most studied Streptomyces species and is an excellent model for studying antibiotic production and cell differentiation. Here, we report construction of S. coelicolor derivatives containing sequential deletions of all the 10 polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) biosynthetic gene clusters and a 900-kb subtelomeric sequence (total c. 1.22 Mb, 14% of the genome). No obvious differences in growth rates and sporulation of the strains were found. An artificially circularized S. coelicolor genome with deletions of total c. 1.6 Mb segments (840-kb for the left and 761-kb for the right arm of the linear chromosome) was obtained. The actinorhodin biosynthetic gene cluster could be overexpressed in some of the constructed strains. PMID- 22670633 TI - Pharmacokinetics of a single oral dose of acyclovir and valacyclovir in North American box turtles (Terrapene sp.). PMID- 22670632 TI - When far becomes near: shared environments activate action simulation. AB - It has been proposed that one means of understanding a person's current behaviour and predicting future actions is by simulating their actions. That is, when another person's actions are observed, similar motor processes are activated in the observer. For example, after observing a reach over an obstacle, a person's subsequent reach trajectory is more curved, reflecting motor priming. Importantly, such motor states are only activated if the observed action is in near (peripersonal) space. However, we demonstrate that when individuals share action environments, simulation of another person's obstacle avoiding reach path takes place even when the action is in far (extrapersonal) space. We propose that action simulation is influenced by factors such as ownership. When an "owned" object is a potential future obstacle, even when it is viewed beyond current action space, simulations are evoked, and these leave a more stable memory capable of influencing future behaviour. PMID- 22670634 TI - Hierarchical three-dimensional microbattery electrodes combining bottom-up self assembly and top-down micromachining. AB - The realization of next-generation portable electronics and integrated microsystems is directly linked with the development of robust batteries with high energy and power density. Three-dimensional micro- and nanostructured electrodes enhance energy and power through higher surface area and thinner active materials, respectively. Here, we present a novel approach for the fabrication of hierarchical electrodes that combine benefits of both length scales. The electrodes consist of self-assembled, virus-templated nanostructures conformally coating three-dimensional micropillars. Active battery material (V(2)O(5)) is deposited using atomic layer deposition on the hierarchical micro/nanonetwork. Electrochemical characterization of these electrodes indicates a 3-fold increase in energy density compared to nanostructures alone, in agreement with the surface area increase, while maintaining the high power characteristics of nanomaterials. Investigation of capacity scaling for varying active material thickness reveals underlying limitations in nanostructured electrodes and highlights the importance of our method in controlling both energy and power density with structural hierarchy. PMID- 22670635 TI - Lessons learned from the first 100 laparoscopic liver resections: not delaying conversion may allow reduced blood loss and operative time. AB - BACKGROUND: The laparoscopic approach to liver resective surgery is slowly spreading to specialized centers. Little is known about factors influencing the immediate postoperative outcome. STUDY DESIGN: The purpose of the study was to evaluate the immediate outcome of laparoscopic liver resection (LLR), with particular emphasis on intraoperative bleeding and conversion. A retrospective analysis of demographic, clinical, and surgical data, including conversion, morbidity/mortality, and hospital stay, of the first 100 patients at our institution undergoing LLR from February 1997 through March 2007 was performed. RESULTS: Indication for LLR was benign lesion in 28 patients, malignancy in 33, and living donation in 39. Seventy-five resections involved two or more segments. Mean blood loss was 120 +/- 127.6 mL. One patient (1%) required transfusion. Mean operative time was 253 +/- 91.6 minutes. No patient died. Postoperative complications occurred in 21 patients. The conversion rate was 17%. Variables related to conversion were American Society of Anesthesiologists Class II, body mass index, cirrhosis, necessity for the Pringle maneuver, and intraoperative blood loss. Conversion did not influence the operative time. Patients with conversion had more complications and a longer hospital stay. CONCLUSIONS: Liver resection by laparoscopy is feasible and safe, implying low intraoperative blood loss. Not perfect physical conditions, cirrhosis, high body mass index, and, intraoperatively, blood loss and the necessity of a Pringle maneuver should be considered risk factors for conversion. A meticulous dissection by bipolar coagulation, Harmonic((r)) (Ethicon) scalpel, and ultrasound dissector, other than the attitude not to delay conversion in difficult cases, may allow for low blood loss without prolongation of operative time, with a possible, slight increase of the conversion rate. PMID- 22670636 TI - Commentary on "A comparison between single-incision and conventional laparoscopic cholecystectomy". PMID- 22670637 TI - Laparoendoscopic single-site versus traditional laparoscopic surgery in patients with cholecystectomy: a meta-analysis. AB - OBJECTIVES: To evaluate the primary outcomes of traditional laparoscopic cholecystectomy (TLC) compared with laparoendoscopic single-site cholecystectomy (LESSC). SUBJECTS AND METHODS: Randomized controlled trials (RCTs) comparing TLC with LESSC were included by a systematic literature research. The inclusion and extraction of the data were completed by two authors independently. Meta-analysis was performed using Review Manager version 5.1.4 software. The clinical outcomes were evaluated by odds ratio (OR) and standard mean difference (SMD) according to the different types of data. Sensitivity and heterogeneity analyses were used to account for rationality of pooling data and sources of heterogeneity. RESULTS: Seven RCTs involving 611 patients met the predefined inclusion criteria. The cosmetic score of the LESSC group was significantly higher at 1 week (SMD = 0.48; 95% confidence intervals [CI] 0.24, 0.73; P = .0001), 2 weeks (SMD = 0.87; 95% CI 0.61, 1.13; P < .00001), and 1 month (SMD = 0.88; 95% CI 0.62, 1.44; P<.00001) postoperatively. However, LESSC showed a lesser physical quality of life (PQOL) score at 3 days (SMD = -0.28; 95% CI -0.52, -0.44; P = .02), 1 week (SMD = -0.31; 95% CI -0.55, 0.06; P = .01), and 2 weeks (SMD = -0.30; 95% CI -0.55, -0.05; P = .02) postoperatively. There was no significant difference between the two groups in operating time, perioperative complication, intraoperative blood loss, postoperative hospital stay, Visual Analog Scale pain score, and PQOL on 1 day, 5 days, and 1 month postoperatively. CONCLUSION: LESSC is associated with a higher cosmetic score and a lesser short-term PQOL score compared with TLC. PMID- 22670638 TI - Early surgical outcomes of NiTi endoluminal compression anastomotic clip (NiTi CAC 30) use in patients with gastrointestinal malignancy. AB - BACKGROUND: The NiTi endoluminal Compression Anastomotic Clip (CACTM) 30 (NiTi CAC 30) (NiTi Alloys Technologies, Ltd., Netanya, Israel) is a new device with shape-memory characteristics. We aimed to investigate the safety and early surgical outcomes of NiTi CAC 30 for intestinal anastomosis in patients with gastrointestinal malignancy. SUBJECTS AND METHODS: Fifty patients operated on with NiTi CAC 30 were matched for sex, age, body mass index, operation type (open versus laparoscopy), operation name, and anastomosis type with patients in a control group operated on with a stapling device between November 2009 and May 2010. Early clinical outcomes were investigated. RESULTS: One misfired case of NiTi CAC 30 was excluded. Between the two groups, no significant differences were observed in demographics except for previous abdominal operation history. The results of early clinical outcomes were investigated, including operation time, estimated blood loss, time to first flatus, first defecation, and discharge, and complications. No differences were noted. Postoperatively, migration started in 1 patient between 3 and 5 days, 11 patients between 6 to 7 days, and 37 patients after 8 days. The expulsion of 31 cases occurred between 2 and 3 weeks, postoperatively. The NiTi CAC 30 was expulsed within 1 week in 4 patients and between 1 to 2 weeks in 8 patients. An expulsion occurred in 1 case at over 4 weeks. No problems related to early migration and expulsion were observed, and no anastomotic leakage and bleeding occurred. CONCLUSIONS: Intestinal anastomosis with the NiTi CAC 30 was safe and feasible without anastomotic leakage and reoperation compared with the stapling technique. PMID- 22670639 TI - Intravesical methylene blue facilitates precise identification of the diverticular neck during robot-assisted laparoscopic bladder diverticulectomy. AB - BACKGROUND: The aim of this report is to describe our surgical technique for robot-assisted laparoscopic bladder diverticulectomy. In this technique, methylene blue is instilled into the bladder to aid in intra-abdominal identification of the diverticular neck. SUBJECTS AND METHODS: We retrospectively reviewed the records of patients who underwent robot-assisted bladder diverticulectomy by a single surgeon. RESULTS: Between September 2008 and January 2011, 5 patients successfully underwent robot-assisted laparoscopic bladder diverticulectomy using 1% intravesical methylene blue. All cases were completed without intraoperative complication or need for open conversion. Mean operative time was 216 minutes, with a mean estimated blood loss of 45 mL. Patients were discharged 1-2 days following surgery. No patient experienced a perioperative complication. CONCLUSIONS: The robot-assisted approach for bladder diverticulectomy is a viable alternative to both open and laparoscopic surgery. The use of intravesical methylene blue greatly aids in identification of the diverticular neck during this procedure. PMID- 22670640 TI - Health worker recruitment and deployment in remote areas of Indonesia. AB - CONTEXT: Providing health care in remote and very remote areas has long been a major concern in Indonesia. In order to improve access to quality health care for residents in these areas, various policies on recruitment and deployment of health workers have been implemented, among them compulsory service, contracted staff and the Special Assignment of strategic health workers. ISSUE: Indonesia's difficult geography presents great challenges to health service delivery and most health workers prefer to serve in urban areas, resulting in an uneven distribution of health workers and shortages in remote areas. Great efforts have been made to mobilize health human resources more equitably, including placement schemes for strategic health workers and contracted staff, combined with an incentive scheme. While these have partially addressed the severe shortage of health workers in remote areas, current government policies were reviewed in order to clarify the current situation in Indonesia. LESSONS LEARNED: The Contracted Staff and Special Assignment of Strategic Health Workers programs show have made a significant contribution to improving the availability of health workers in Indonesia's remote areas. As these two programs used financial incentives as the main intervention, other non-financial interventions should also be trialed. For example, incentives such as the promise of a civil servant appointment or the provision of continuing professional education, as well as the recruitment of rural-background health workers may increase the willingness of health staff to serve in the remote and very remote areas of Indonesia. PMID- 22670641 TI - The impact of children's perception of an activity as play rather than not play on emotional well-being. AB - BACKGROUND: As an important aspect of health and development, a number of policy and practice initiatives across education, health and social care are aimed at increasing children's emotional well-being. Links have been made between young children's emotional well-being and play although empirical evidence is limited. This paper demonstrates that when children perceive an activity as play, they show more signs of emotional well-being than when they perceive the same activity as not play. METHODS: One hundred and twenty-nine children aged between 3 and 5 years participated in the study. The cues children use to differentiate play and not play were used to create an activity session that was 'like play' and an activity session that was 'not like play'. The activity itself remained constant. Children were allocated to either of the activity session types alternately and emotional well-being was measured using the Leuvens Involvement Scale. RESULTS: There was a significant difference in the level of emotional well-being displayed by children in the two activity session types. Children who undertook the 'like play' activity scored significantly higher than children who undertook the same activity but 'not like play'. Detailed observational analysis also showed increased behavioural indicators relating to emotional well-being among children participating in the 'like play' rather than 'not like play' activity session. CONCLUSION: Children demonstrate increased emotional well-being when they perceive an activity as play rather than not play. Findings support the proposition that play can be seen as an observable behaviour but also as a mental state. As well as providing important evidence as to the value of play for enhancing children's emotional well-being, findings are discussed in relation to professional practice in children's services. The paper highlights the training needs of practitioners to enable them to understand children's views about play and use this information to create playful situations which maximize the developmental potential of play. PMID- 22670642 TI - Synthesis of PDE IVb Inhibitors. 3. Synthesis of (+)-, (-)-, and (+/-)-7-[3 (cyclopentyloxy)-4-methoxyphenyl]hexahydro-3H-pyrrolizin-3-one via reductive domino transformations of 3-beta-carbomethoxyethyl-substituted six-membered cyclic nitronates. AB - Simple three-step asymmetric and racemic syntheses of GlaxoSmithKline's highly potent PDE IVb inhibitor 1 were developed. The suggested approach is based on reductive domino transformations of 3-beta-carbomethoxyethyl-substituted six membered cyclic nitronates, which are easily accessed by a stereoselective [4 + 2] cycloaddition of an appropriate nitroalkene to vinyl ethers. In vitro studies of PDE IVb inhibition by enantiomeric pyrrolizidinones (+)-1 and (-)-1 were performed. PMID- 22670643 TI - Green tea (Camelia sinensis) mediated suppression of IgE production by peripheral blood mononuclear cells of allergic asthmatic humans. AB - Recent studies in our laboratory demonstrated the suppression of immunoglobulin E (IgE) production by green tea extract (GTE) in U266 cells. However, the effects of GTE or one of its components (EGCG) on IgE production by human peripheral blood mononuclear cells (PBMC) are unknown. PBMC (1.5 * 106) obtained from serum IgE+, allergic asthmatic patients, were cultured +/- GTE (1-100 ng/ml) or purified EGCG (0.5-50 ng/ml), and IgE levels were determined on day 10 by enzyme linked immunosorbent assay (ELISA). High levels of IgE were detected in supernatants of the PBMC cultures on day 10. When GTE was included in vitro, IgE production by PBMC was suppressed on day 10, compared with control. Purified EGCG included in vitro also suppressed IgE production, but at lower levels, compared with control. This study demonstrates that GTE and its major catechin, EGCG, have immunoregulatory effects on human IgE responses. PMID- 22670644 TI - Olympic and world sport: making transnational society? AB - This paper introduces the special issue of the British Journal of Sociology on the subject of the transnational aspects of Olympic and world sport. The special issue is underpinned by the perspective that because sport provides a space for the forging of transnational connections and global consciousness, it is increasingly significant within contemporary processes of globalization and the making of transnational society. In this article, we examine in turn eight social scientific themes or problems that are prominent within the special issue: globalization, glocalization, neo-liberal ideologies and policies, transnational society, securitization, global civil society, transnational/global public sphere, and fantasy/imagination. We conclude by highlighting five 'circles' of future research inquiry within world sport that should be explored by social scientists. PMID- 22670645 TI - Mapping the global football field: a sociological model of transnational forces within the world game. AB - This paper provides a sociological model of the key transnational political and economic forces that are shaping the 'global football field'. The model draws upon, and significantly extends, the theory of the 'global field' developed previously by Robertson. The model features four quadrants, each of which contains a dominant operating principle, an 'elemental reference point', and an 'elemental theme'. The quadrants contain, first, neo-liberalism, associated with the individual and elite football clubs; second, neo-mercantilism, associated with nation-states and national football systems; third, international relations, associated with international governing bodies; and fourth, global civil society, associated with diverse institutions that pursue human development and/or social justice. We examine some of the interactions and tensions between the major institutional and ideological forces across the four quadrants. We conclude by examining how the weakest quadrant, featuring global civil society, may gain greater prominence within football. In broad terms, we argue that our four-fold model may be utilized to map and to examine other substantive research fields with reference to globalization. PMID- 22670646 TI - Planning for the worst: risk, uncertainty and the Olympic Games. AB - Security for the Olympic Games has become undeniably visible in recent years. A certain degree of this visibility became unavoidable after the 1972 Munich Olympics when military personnel and hardware became standard elements of Olympic security. Yet, this visibility is qualitatively different today in that it is often deliberately fashioned for public consumption. This article argues that this expressive dimension of security at the Games provides a window into wider issues of how authorities 'show' that they can deliver on the promise of maximum security under conditions of radical uncertainty. The latter sections of this article examine three ways in which this promise is extended: the discursive work of managers of unease, the staging of highly stylized demonstration projects, and the fabrication of fantasy documents. We focus on how officials emphasize that they have contemplated and planned for all possible security threats, especially catastrophic threats and worst-case scenarios. Actually planning for these events is epistemologically and practically impossible, but saying and showing that authorities are 'planning for the worst' are discursive ways of transforming uncertainty into apparently manageable risks that are independent of the functional activities they describe. As such, our analysis provides insights into the much broader issue of how authorities sustain the appearance of maximum security in order to maintain rhetorical control over what are deemed to be highly uncertain and insecure situations. Such performances may paradoxically amplify uncertainty, thus recreating the conditions that foster the ongoing securitization of everyday life. PMID- 22670647 TI - The regeneration games: purity and security in the Olympic city. AB - This paper examines the wider social impacts of hosting the London 2012 Olympic Games and its 'legacy' ambitions in East London, emphasizing securitization as an inbuilt feature of the urban regeneration project. Drawing on extensive original empirical research, the paper analyses the modalities of Olympic safety and security practices within the Olympic Park itself and their wider impact, while also connecting this research to theorization and debates in urban sociology and criminology. In this complex setting, a raft of formal and informal, often subtle, regulatory mechanisms have emerged, especially as visions of social ordering focused on 'cleansing' and 'purifying' have 'leaked out' from the hyper securitized 'sterilized' environment of the Olympic Park and become embedded within the Olympic neighbourhood. In such complex circumstances, applying Douglas' (1966) work on purity and danger to the spatial realm provides a key conceptual framework to understand the form and impact of such processes. The imposition of order can be seen to not only perform 'cleansing' functions, but also articulate multiple symbolic, expressive and instrumental roles. PMID- 22670648 TI - The bid, the lead-up, the event and the legacy: global cultural politics and hosting the Olympics. AB - Hosting mega sport events, especially the Olympics, demands an extensive engagement with global civil society given the voluntary, highly mediated exposure of host cities and nations to the world. The philosophy of Olympism requires ethical authority in demonstrating 'fitness' to host the Games, so demanding intensive strategic image management. Offensive and defensive mobilization of image-dependent 'species of power' in the field of sport (in a Bourdieusian sense) in conducting 'wars of position and movement' (following Gramsci) within global civil society are, then, crucial features of competitive manoeuvres around staging major sport events. The main empirical focus of this article is on the case of the Sydney 2000 ('Millennial') Games, in illustrating the socio-political dynamics of bidding and hosting in the context of a major civil societal matter of concern - Australia's continuing failure to achieve reconciliation with, and equality for, its indigenous peoples. Ironically, though, it was in the domain of human rights that Sydney had an advantage over its closest competitor in the 1993 bidding process - China. The strategies deployed to secure the consent of Australian Aborigines to the Games are addressed in analysing the means by which the Sydney 2000 Games avoided major disruption and international criticism. A second, briefer case analysis is then presented of the disputation concerning Beijing's successful bid for the 2008 Olympics, which saw them influentially described by one (US) political activist as the 'Genocide Games' and the subject of international protests surrounding the Torch Relay. It is concluded that the contrasting levels of public, mediated discord in these two Olympiads in which human rights were key issues related, significantly though not exclusively, to the Chinese authorities' difficulties in 'winning consent' through strategic incorporation of the most conspicuous, non state oppositional forces within Western-dominated global civil society in its most immediate, unruly, and mediatized form. PMID- 22670649 TI - Human rights and the Beijing Olympics: imagined global community and the transnational public sphere. AB - The Olympic Games are increasingly used by non-governmental organizations to demand transnational forms of accountability from public authorities. This article assesses the effectiveness of transnational public opinion surrounding the Beijing 2008 Olympics, when the pressure of Western public opinion was exerted upon the government of the world's most populous non-Western nation to improve its human rights record. Utilizing the concepts of 'imagined global community' and 'transnational public sphere', it finds that the Olympic Games had helped to call into existence a transnational public that ran up against the obstacle posed by the incomplete formation of supra-national forms of governance. The International Olympic Committee, a non-governmental organization, was a weak substitute. Because of the strong desire of Chinese people to take part in transnational deliberations, the article concludes with optimism about the potential of transnational public spheres that include Chinese people to develop toward more effective forms of transnational governance. But the IOC must strengthen the voice of its non-Western members, and Western interlocutors, including the media, must accept their share of the responsibility for creating the conditions for egalitarian dialogue. PMID- 22670650 TI - 'Our struggles are bigger than the World Cup': civic activism, state-society relations and the socio-political legacies of the 2010 FIFA World Cup. AB - South Africa's hosting of the 2010 FIFA World Cup saw a large number of public demonstrations, strikes and other forms of civic campaigning. World Cup activism was both preceded and followed by extensive and intensifying public unrest and industrial action that in the period before the tournament, threatened to derail the event. This paper assesses the motivations, forms and implications of the activism during South Africa's staging of the FIFA finals and interprets them against the larger context of shifting state-society relations in the country. There are two purposes to the analysis. First, to explore the underlying internal social forces that gave shape to the protests at the time, and the possible influence of the exogenous politics of mega-event social mobilization. Second, the implications and outcomes of these dynamics for longer term socio-political processes in the country are considered. The activism displayed many of the features of the politics of contestation of sport mega-events today. Importantly, however, the activism stemmed from a particular systemic dynamic and reflected changing relations in the post-apartheid political community. Therefore, while the World Cup was used as a strategic opportunity by many advocacy groups, it was one that rather fleetingly and ambivalently presented an additional platform to such groups in an otherwise on-going set of political battles. Rather than a strong case study of sport's transformative capacity, the civic campaigning during South Africa's World Cup demonstrates the way a sport mega-event can be used as a strategic entry point by civil society groups in their engagement with the state, although this can occur with greater or lesser success. PMID- 22670651 TI - Football's coming home?: Digital reterritorialization, contradictions in the transnational coverage of sport and the sociology of alternative football broadcasts. AB - This article critically utilizes the work of Manuel Castells to discuss the issue of parallel imported broadcasts (specifically including live-streams) in football. This is of crucial importance to sport because the English Premier League is premised upon the sale of television rights broadcasts to domestic and overseas markets, and yet cheaper alternative broadcasts endanger the price of such rights. Evidence is drawn from qualitative fieldwork and library/Internet sources to explore the practices of supporters and the politics involved in the generation of alternative broadcasts. This enables us to clarify the core sociological themes of 'milieu of innovation' and 'locale' within today's digitally networked global society. PMID- 22670652 TI - Fans, homophobia and masculinities in association football: evidence of a more inclusive environment. AB - This article draws on 3,500 responses from fans and professionals involved in association football (soccer) to an anonymous online survey posted from June 2010 to October 2010 regarding their views towards gay footballers. The overall findings are that, contrary to assumptions of homophobia, there is evidence of rapidly decreasing homophobia within the culture of football fandom. The results advance inclusive masculinity theory with 93 per cent of fans of all ages stating that there is no place for homophobia within football. Fans blame agents and clubs for the lack of openness and challenge football's governing organizations to oppose the culture of secrecy surrounding gay players and to provide a more inclusive environment to support players who want to come out. PMID- 22670654 TI - Prevention case management improves socioeconomic standing and reduces symptoms of psychological and emotional distress among transgender women. AB - Urban transgender women often experience several sociocultural co-factors which contribute to their risk of HIV infection. A transgender-specific HIV Prevention Case Management (PCM) intervention was implemented in a community HIV prevention setting and targeted reducing sex work and homelessness, increasing legal employment and income, and reducing psychological and emotional distress symptoms. Sixty high-risk transgender women were enrolled in the ten-session PCM intervention. Participants completed approximately nine out of the ten sessions (M = 8.7; SD = 2.6) and six-month follow-up evaluations were completed with 97% of the participants. Findings from baseline to follow-up evaluations demonstrated a decrease in homelessness (31.0% vs. 10.3%, p<0.01), less reliance on exchange sex as a primary source of income (41.4% vs. 22.4%, p < 0.05), and significant decreases in symptom complaints across multiple Brief Symptom Inventory sub scales, including depression, hostility, phobic anxiety, and psychoticism (all significant at p<0.05). Further, socioeconomic improvements following the intervention were significantly associated with psychological and emotional gains. The study suggests that adding a culturally appropriate PCM intervention in a community setting is beneficial in addressing co-factors for HIV infection as well as psychological and emotional distress symptoms among this extremely high-risk population. PMID- 22670655 TI - Early cartilage degeneration in a rat experimental model of developmental dysplasia of the hip. AB - Osteoarthritis (OA) is a common long-term complication of developmental dysplasia of the hip (DDH) that is associated with a higher incidence of OA. In addition, the age of onset of OA in DDH patients is significantly younger than in the general population. In order to investigate the early degeneration in DDH cartilage, we used a rat DDH model that was established by the straight-leg swaddling position. The hips were isolated from the DDH model rats and an untreated control group at postnatal weeks 2, 4, 6, and 8. Histology and proteoglycan levels were observed in articular cartilage using Safranin O staining. Biomarkers of cartilage degeneration, including type X collagen and matrix metalloproteinase (MMP)-13, were assessed using immunohistochemistry and quantitative real-time polymerase chain reaction. In addition, expressions of ADAMTS-4 and ADAMTS-5 were studied using quantitative real-time polymerase chain reaction at different ages. DDH rats showed decreased proteoglycans and derangement of chondrocytes when compared with the control group. Collagen X and MMP-13 expressions were higher in the superficial zone of DDH rats than in that of controls (p < 0.05), and the increase was age-dependent. mRNA expression of Collagen X and MMP-13 showed similar results (p < 0.05). A significant increase in mRNA expression of ADAMTS-5 was found in the DDH model cartilage at 8 weeks (p < 0.05). However, no change was observed in ADAMTS-4 expression. This study shows that degenerative cartilage changes occur at an early stage in the rat DDH model and become aggravated with age. PMID- 22670656 TI - Determination of polycyclic aromatic hydrocarbons in edible seafood by QuEChERS based extraction and gas chromatography-tandem mass spectrometry. AB - A high-throughput analysis of polycyclic aromatic hydrocarbons (PAHs) in edible seafood using QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) based extraction and gas chromatography-tandem mass spectrometry (GC-MS/MS) was developed and validated in 4 seafood matrices--crab, finfish, oyster, and shrimp. The extraction employs QuEChERS with dispersive solid phase extraction (dSPE) using cleanup sorbent that includes C18. The acetonitrile extract is partitioned into hexane and analyzed by GC-MS/MS. The procedure was validated by spike recovery experiments of 15 parent and 5 substituted PAHs at 5ppb and 25 ppb levels in the 4 matrices. Recoveries were 71%-130% with RSDs less than 14%. The limit of quantitation (LOQ) for benzo[a]pyrene are 0.4-2.5 ppb depending on matrix. For all 15 parent PAHs the LOQs are less than 10% of the Levels of Concern established by the U.S. Food and Drug Administration. Good recoveries were also achieved in aged spikes at 5 ppb level in oyster and shrimp. Method accuracy was further evaluated by analyzing NIST Standard Reference Material 1974b. Ten of 14 incurred PAHs corresponding to the parent compounds in the present study fell within the control limits established by the National Oceanic and Atmospheric Administration. Using the present method approximately 20 samples every 24 h can be analyzed with confirmation. PRACTICAL APPLICATION: The presented analytical method could be used for seafood safety assessments to examine petroleum contaminant levels in edible seafood after an oil spill. The method is fast and sensitive. PMID- 22670657 TI - Serum FGF21 and RBP4 levels in patients with chronic hepatitis C. AB - INTRODUCTION: Fibroblast growth factor-21 (FGF21) regulates glucose, lipid, and energy homeostasis. Retinol-binding protein-4 (RBP4) controls metabolic and proliferative cell functions. AIMS AND METHODS: Aims of the study were to assess (1) serum FGF21 and RBP4 levels in 75 non-obese chronic hepatitis C (CHC) patients and 41 healthy controls similar in age and BMI; (2) the relationship between their serum concentration and insulin resistance, liver histology, and biochemical parameters; (3) their effectiveness as diagnostic markers. RESULTS: FGF21 levels increased significantly in CHC patients compared with controls (p = 0.04). CHC patients with steatosis had significantly higher FGF21 levels compared with those without steatosis (p = 0.01). FGF21 concentration was positively related to steatosis grade (r = 0.39, p = 0.007). RBP4 levels did not differ between CHC patients and controls, but were negatively associated with necro inflammatory activity grade (r = (-0.34), p = 0.04), with significantly higher levels in patients with minimal inflammatory activity (G1 vs. G2/3, p < 0.001; G1 vs. G2, p = 0 < 001; G1 vs. G3, p = 0.01). After stepwise linear regression analysis adjusting for potential confounders, RBP4 levels retained their independent significance as a predictor of necro-inflammatory activity (beta = 0.31; t = -2.15, p = 0.035) and FGF21 levels as a predictor of steatosis (beta = 0.34; t = 2.31, p = 0.024). Serum FGF21 correlated with serum RBP4 levels (r = 0.32, p = 0.02). CONCLUSIONS: Serum FGF21 levels increased in CHC patients, especially in those with steatosis and were associated with steatosis grade. FGF21 seems to be a useful diagnostic marker in determining hepatic steatosis in CHC. A negative association between serum RBP4 and necro-inflammatory activity indicates that disease severity may determine RBP4 levels. PMID- 22670658 TI - Headache medications and bone health. PMID- 22670659 TI - Alcohol, violence, and the media. PMID- 22670660 TI - Systematic review: are lymphocytic colitis and collagenous colitis two subtypes of the same disease - microscopic colitis? AB - BACKGROUND: Despite similar clinical symptoms, collagenous colitis (CC) and lymphocytic colitis (LC) are considered two distinct disease entities. AIM: To compare pathoanatomical findings, clinical presentations, risk factors, course of diseases and response to treatment in CC and LC to establish whether they could be subtypes of the same disease, microscopic colitis (MC). METHODS: The MEDLINE was searched for CC, LC and MC, and clinical studies of >20 patients were included. Pooled results with 95% confidence intervals were calculated based on the number of patients. RESULTS: An abnormal number of intraepithelial lymphocytes are found in 45% (40-50%) with CC, and an abnormal subepithelial collagen band in 16% (13-20%) with LC suggesting a histological overlap. The incidence of CC and LC has increased in parallel. Mean age (CC 63 years; LC 60 years) and clinical presentation are indistinguishable, and females are predominant in CC (77%; 75-79%) as well as LC (68%; 66-70%). Risk factors such as nonsteroid anti-inflammatory drugs consumption CC 39% (36-42%); LC 32% (29-35%) are similar and prevalence of concomitant autoimmune diseases such as coeliac disease (CC 5%; CI: 4-6% and LC 7%; CI: 6-9%) do not differ. Bile acid diarrhoea is highly prevalent in CC (41%; 37-45%) and LC (29%; 24-34%). The effect of budesonide is identical. CONCLUSIONS: CC and LC could be considered histological subtypes of the same disease, MC. To facilitate recruitment to clinical trials, all MC patients could be included in future trials and stratified for subtypes. PMID- 22670661 TI - Integrated effects of light intensity and fertilization on growth and flavonoid accumulation in Cyclocarya paliurus. AB - Cyclocarya paliurus has been used for drug formulations and ingredients in functional foods in China. Field studies were conducted to examine the relationships between environmental factors and flavonoid accumulation. A split plot randomized design was used to establish three shading treatments and three fertilization levels, and growth parameters and flavonoid contents were detected. The greatest biomass production was achieved in intermediate shade and fertilization treatment, and leaf production per seedling increased by 139.5% compared to the treatment without shade and fertilization. Overall, shade and fertilization had a significantly negative effect on contents of total flavonoid, kaempferol, quercetin, and isoquercitrin in leaves of C. paliurus. However, the greatest accumulation of total flavonoid in the leaves was observed in intermediate shade and fertilization treatment, achieving 364.4 g/plant. The results suggest that manipulating the field growing conditions and optimizing the silvicultural system would be important for obtaining the greatest yield of targeted health-promoting substances. PMID- 22670662 TI - Natural killer cells: a review of manufacturing and clinical utility. PMID- 22670663 TI - Pegylated fluorescent peptides as substrates of proteolytic enzymes. AB - In this work the efficient and simple method of improvement specificity and solubility of low molecular weight proteinase substrates is described. The series of fluorescent substrates of selected proteolytic enzymes (neutrophil elastase, cathepsin G and proteinase 3 along with human airway trypsin like protease) were synthesized and modified by selective pegylation by the attachment of 2-(2-(2 aminoethoxy)ethoxy)acetic acid. Modification of the C-terminal carboxyl group resulted in the decrease in the specificity constants (k(cat)/K(M)) for all obtained analogues. The covalent attachment of PEG to N-terminal amino group has the opposite effect, as the increase in specificity constant was observed for all studied compounds. This outcome was pronounced the most for proteinase 3 substrate PEG-ABZ-Tyr-Tyr-Abu-ANB-NH2, whose catalytic constant (k(cat)) increased over three fold. The introduction of PEG moieties at both C- and N terminal yielded the substrates with lower specificity constants. For substrate (ABZ-Arg-Gln-Asp-Arg-ANB-NH2) the influence of the PEG chain length on its kinetic parameters was investigated. Elongation of the PEG chain at N-terminal of this peptide decreased the specificity constant. In addition to the effect of pegylation on the kinetic parameters of the studied substrates, the introduced modifications significantly improved their solubility in buffer solutions applied for enzymatic investigations. PMID- 22670664 TI - (Acyloxy)alkoxy moiety as amino acids protecting group for the synthesis of (R,R) 2,7 diaminosuberic acid via RCM. AB - A new synthetic pathway is described to prepare asymmetrically protected 2,7 diaminosuberic acid. This strategy exploits (acyloxy)alkoxy promoiety as protecting group and RCM reaction using second generation Grubbs catalyst and provides the trans isomer of (2R,7R)-7-(((9H-fluoren-9-yl)methoxy)carbonylamino) 2-(tert-butoxycarbonylamino)-8- methoxy-8-oxooct-4-enoic acid, which was in turn reduced to obtain (2R,7R)-7-(((9H-fluoren-9-yl)methoxy)carbonylamino)- 2-(tert butoxycarbonylamino)-8-methoxy-8-oxooctanoic acid. PMID- 22670665 TI - Expression of heme oxygenase-1 in response to proteasomal inhibition. AB - Heme oxygenase-1 (HO-1) is an antioxidant, antiapoptotic and cytoprotective enzyme, catalysing the degradation of heme to carbon monoxide, biliverdin and ferrous iron. Recent studies indicated that expression of HO-1 is under the control of proapoptotic transcription factor p53 and antioxidant transcription factor Nrf2. Whether each of these transcription factors act independently or there is a cooperation between them in inducing HO-1 expression remains to be elucidated. In this study, we examined the expression of HO-1 in B16F10 melanoma and 4T1 breast cancer cells after cell exposure to proteasome inhibitors. We found that HO-1 protein level is increased by about 70% in p53-wt B16F10 cells in response to proteasome inhibitor MG132 after 6 h. Likewise, a 6.8 fold increase in HO-1 level was observed after cell exposure to the highly specific proteasome inhibitor bortezomib after 6 h of treatment in B16F10 cells. Whereas no induction of HO-1 was observed in p53-null 4T1 cells after treatment with bortezomib for 6 h. Next, we aligned HO-1 untranslated region with a consensus p53-responsive element. This bioinformatic analysis identified a p53-responsive element within the untranslated region of HO-1. Then, we examined HO-1 expression after a prolonged exposure to bortezomib in both B16F10 and 4T1 cell. These analyses similarly indicated that HO-1 is strongly induced in B16F10 cells in a dosedependent; contrary to our expectations, a strong induction of HO-1 is also observed in 4T1 cells. Therefore, it is concluded that HO-1 expression is under the control of p53 during early time points of proteasomal inhibition. However, during prolonged incubation with proteasome inhibitors, HO-1 expression can be induced in a p53-independent manner, suggesting participation of other protein(s) with longer half-lives. PMID- 22670666 TI - Predicting the metabolic pathways of small molecules based on their physicochemical properties. AB - How to correctly and efficiently map small molecule to its possible metabolic pathway is a meaningful topic to metabonomics research. In this work, a novel approach to address this problem was introduced to encode physicochemical properties of small molecules. Based on this encoding method, a two stage feature selection method called mRMR-FFSAdaBoost was adopted to map small molecules to their corresponding metabolic pathways possible. As a result, the accuracies of 10-folds cross-validation test and independent set test for predicting the metabolic pathways of small molecules reached 83.88% and 85.23%, respectively. An online server for predicting metabolic pathways of unknown small molecules as described in this paper is accessible at http://chemdata.shu.edu.cn:8080/PathwayPrediction/. PMID- 22670667 TI - The stability of wild-type and deletion mutants of human C-terminus Hsp70 interacting protein (CHIP). AB - Carboxyl terminus of Hsp70 interacting protein (CHIP) is a dimeric co-chaperone involved in providing an appropriate balance between the synthesis and degradation of proteins, which is essential for normal cellular growth and function. Previous work has shown that CHIP, but not its isolated domains, has chaperone activity that is enhanced by heat. In this work, we investigate how heat and urea affect the stability of its domains. We found that the deletion mutant containing the TPR domain, which binds to chaperones Hsp70 or Hsp90, was monomeric and showed similar folding and stability to WT, while the mutant containing the U-box ubiquitin ligase domain was dimeric but had very low stability. The deletion mutants appeared to maintain most of their structure compared to the WT protein, but the regions around the tryptophan residues, which are at the interface of the domains in the WT structure, appeared to be more unfolded, which indicated that the region of contact between domains is likely important for the chaperone function. PMID- 22670668 TI - Synthesis and in vitro study of the anticancer activity of new analogs of octreotide. AB - Based on the structure of Octreotide (SMS 201-995) some modified at positions 5 with Dap (diaminopropanoic acid), Dab (diaminobutanoic acid) and Orn new C-amide analogs were synthesized. The Thr6 was replaced by unnatural amino acids Tle (t leucine). The cytotoxic effects of the novel compounds were tested in vitro against a panel of human tumor cell lines. All investigated compounds exhibited different concentration-dependent antiproliferative effects against the HT-29, MDA-MB-231, HepG2 and HeLa cell lines after 24 h treatment. The compound 2 (D-Phe c(Cys-Phe-D-Trp- Dap-Tle-Cys)-Thr-NH2) had antiproliferative effects on MDA-MB 231 cells with the IC50 0.03 mM. The HeLa and HepG-2 cells were most sensitive towards tested compounds at various concentrations. Results demonstrated that the peptide analogs 3 (D-Phe-c(Cys-Phe-D-Trp-Lys-Tle-Cys)-Thr-NH2), 4 (D-Phe-c(Cys Phe-D-Trp-Orn-Tle-Cys)-Thr-NH2) and 5 (RC-102) exert the most pronounced inhibition of the cell vitality up to 77% at higher concentrations and were not toxic to the normal Lep-3 cells. PMID- 22670669 TI - Functional and structural characterization of Helicobacter pylori ClpX: a molecular chaperone of Hsp100 family. AB - ClpX is a general stress protein which belongs to the heat shock protein, Clp/Hsp100 family of molecular chaperones. ClpX, in association with ClpP degrades proteins in an ATP dependent manner. Some members of the Clp family have been shown to be involved in the pathogenesis of many bacteria. The Helicobacter pylori genome demonstrates the presence of ClpX along with ClpA, ClpB and ClpP, the other members of the caseinolytic protease family. H. pylori ClpX is a 386 amino acid long protein. In this study, we have over-expressed H. pylori ClpX in E. coli, purified the recombinant protein to homogeneity and functionally characterized it. The recombinant H. pylori ClpX showed an inherent ATPase activity and prevented the heat induced aggregation of a model protein in vitro. The chaperonic activity of H. pylori ClpX was dependent on ATP hydrolysis and involved hydrophobic interaction with the substrate protein. Biophysical studies reveal the secondary structure tolerance of ClpX at various temperatures and in the presence of guanidine hydrochloride. The study demonstrates that H. pylori ClpX manifests chaperonic activity in the absence of any adaptor protein. PMID- 22670670 TI - Comparative proteomic analysis of colon cancer cell HCT-15 in response to all trans retinoic acid treatment. AB - Colon cancer is one of the most common malignances. In vitro and in vivo study show that retinoic acids inhibit a wide variety of cancer cells but the molecular mechanism of their anti-tumor effects are not yet fully understood. Alltrans retinoic acid (ATRA), an isomer of retinoic acid, can inhibit the proliferation of HCT-15 human colon cancer cell line. A proteomic analysis was performed using HCT-15 treated with ATRA to further elucidate the retinoic acid signaling pathway and its anti-tumor effect mechanism. MTT results showed that the growth of HCT-15 cells were significantly inhibited by ATRA. The alkaline phosphatase activity assay showed that ATRA failed to induce the differentiation of HCT-15. The DNA ladder detection showed that ATRA induced apoptosis in HCT-15. Two-dimensional gel electrophoresis coupled with MALDI-TOF/TOF mass spectrometry identified 13 differentially expressed proteins in HCT-15 cells after all-trans retinoic acid treatment. Among the identified differentially expressed proteins, there were four scaffold proteins (YWHAE, SFN, YWHAB, and YWHAZ), two ubiquitin modification related proteins (ISG-15 and UBE2N), two translational initiation factors (EIF1AX and EIF3K), two cytoskeleton related proteins (EZRI and CNN3), two proteinmodification related proteins (TXNDC17 and PIMT), and one enzyme related to phospholipid metabolism (PSP). Both EZRI and UBE2N were rendered to western blot validation and the results were consistent with the two-dimension electrophoresis analysis. In this study, the differentially expressed proteins in HCT-15 treated by ATRA were identified, which will assist the further elucidation of the anti-tumor mechanism of retinoic acids. PMID- 22670672 TI - Identification of a novel antifungal peptide with chitin-binding property from marine metagenome. AB - A novel antifungal peptide with 36 amino acids was identified by functional screening of a marine metagenomic library. The peptide did not show similarity with any existing antimicrobial peptide sequences in the databank. The108 bp ORF designated as mmgp1 was cloned and expressed in Escherichia coli BL21 (DE3) using pET expression system. Mass spectrometry analysis of the purified recombinant peptide revealed a molecular mass of 5026.9 Da. The purified recombinant peptide inhibited the growth of Candida albicans and Aspergillus niger. The peptide was predicted to adopt alpha- helical conformation with an extended coil containing a ligand binding site for N-acetyl-D-glucosamine. The alpha- helicity of the peptide was demonstrated by circular dichroism spectroscopy in the presence of chitin or membrane mimicking solvent, trifluoroethanol. The chitin binding property of the peptide was also confirmed by fast performance liquid chromatography. PMID- 22670671 TI - Mobilization of reserve proteins and activities of cysteine peptidases during germinative and post-germinative events of cowpea seeds. AB - Cysteine peptidases are the best characterized peptidases among those involved with storage protein mobilization during seed germination. In the present work we show two major groups of cysteine peptidase activities, one of higher (55 to 97 kDa) and other with lower (15 to 20 kDa) molecular masses which are temporally activated after 24 and 48 HAI, respectively, in germinating cowpeas. The former group is found both in protein bodies and in cytoplasmic fraction, while the latter is mostly present outside protein bodies. A third cysteine peptidase activity of ~37 kDa was specifically active at quiescent cotyledons and at 12 and 60 hours after imbibition (HAI). Main peptidase activities of albumin fractions were synchronizedly detected with radicle emergence at 36 HAI. Major vicilin mobilization was more pronounced from 60 HAI onwards and steadily increased until 144 HAI, when low levels of the smallest vicilin subunit were present. Cysteine peptidases were susceptible to iodoacetamide, E-64, iodoacetic acid, pCMB and beta-mercaptoethanol, except for the ~37 kDa peptidase, which was not affected by any of the inhibitors. By a two-dimensional native/SDS-PAGE combination it was observed an apparent linear arrangement of protein breakdown products as well as of peptidase activity spots. The finding may indicate a complex set of sequential proteolytic events where peptidases induce or activate new peptidases, which may act upon different aggregates or zymogens, and these hydrolysis products appear in a line of constant decreasing Rf x Mr ratio. PMID- 22670673 TI - Intrinsic vs environment driven equilibrium folding transitions in GTPase effector domain of dynamin: NMR insights. AB - Relative importance of the intrinsic properties of the polypeptide chain vis-a vis the environmental influences, in driving the folding of a protein, has been a subject of extensive debate and investigation. Folding/misfolding lead to self association in many systems, which have biological functional significance. We compare here, the NMR derived equilibrium folding transitions driven under different environmental conditions in the GTPase Effector Domain of dynamin, which self-associates into megadalton size species. We conclude that though hierarchy of folding and association of GED is substantially influenced by the solvents, these properties, to a good extent are also driven by intrinsic properties of the polypeptide chain, and the regions that form secondary structures, the types of secondary structures formed in those regions, and finally the regions that participate in the self-association are the same, indicating near neighbor interactions would have a telling effect on the final outcome of the folding process. These observations would open a new reliable frontier for elucidating the multiple folding trajectories and consequent self association, by simulations in vacuum, for this protein. PMID- 22670674 TI - MT1-MMP modulates bFGF-induced VEGF-A expression in corneal fibroblasts. AB - The cornea is physiologically avascular. Following a corneal injury, wound healing often proceeds without neovascularization (NV); however, corneal NV may be induced during wound healing in certain inflammatory, infectious, degenerative, and traumatic states. Such states disrupt the physiologic balance between pro-angiogenic and antiangiogenic mediators, favoring angiogenesis. Contributors to such states are matrix metalloproteinases (MMPs), which are key factors in both extracellular matrix remodeling and angiogenesis. Similarly, vascular endothelial growth factor A (VEGF-A) and basic fibroblast growth factor (bFGF) exert pro-angiogenic effects. Here, we elaborate on the facilitative role of MMPs-specifically Membrane Type 1 MMP (MT1-MMP, MMP14)-in corneal NV. Additionally, we provide new insight into the signaling relating to MT1-MMP, Ras, and ERK in the bFGF-induced VEGF-A expression pathways within the corneal fibroblasts. PMID- 22670675 TI - Identification of novel potent inhibitors against Bcl-xL anti-apoptotic protein using docking studies. AB - Bcl-xL protein belongs to BCL-2 family which has either pro- or anti-apoptotic activities owing to their importance in the regulation of apoptosis, tumor genesis and cellular responses to anti-cancer therapy. Bcl-xL permeabilize the outer mitochondrial membrane of cells and inhibit these processes. Protein inhibitor interactions play an important role in regulating the expression of Bcl xL protein. Here, we report the docking studies that resulted in the identification of new inhibitors distinct from the previously reported inhibitor against this protein. The results have been validated using Sybyl surflux docking. New potent inhibitors from docking analysis are pentacyclic triterpenoid derivative (2S,4aR,6aR, 6bS,8aS,10R,12R,12aS,12bR,14bR,E)-10,12-dihydroxy 2,4a,14b-trimethyl-9-((((R)-3,4,5-trihydroxy-6-methyl-2H-pyran- 2 yl)oxy)methylene)-1,2,3,4,4a,5,6,6a,6b,8a,9,10,11,12,12a,12b,13,14b octadecahydropicene-2-car-boxylic acid and 4- alkyl-4-methoxypiperidine derivative 8h (where R= 4-Cl-Ph) that promotes the release of pro-apoptotic proteins from the mitochondria which is a key event in cell death signaling. The compounds form stable complex with protein exhibiting highest binding affinity and Gibbs free energy. Pentacyclic triterpenoid derivatives compound-201 and piperidine derivative compound-39 are potent inhibitors with Ki value of 172.62nM and 175.24 nM high affinity and inhibitory potency. Salt bridge, pi-pi and hydrogen bonding interactions predominantly contribute towards the stability of the complexes. These compounds can further be exploited for their potential to enhance apoptosis. We have established the correlation between the experimental Ki value with our computational inhibition constant. The quantitative predictions in this study provide a scope for further experimental testing giving structural insights into the design and development of novel anticancer drugs. PMID- 22670676 TI - Defensinpred: defensin and defensin types prediction server. AB - Defensins are considered to play an important role in the innate immune system of virtually all life forms, from insects and plants to amphibians and mammals. They are classified into alpha, beta and theta-defensins. Fast and accurate computational prediction of defensin and defensin types will help in annotating unidentified defensin novel peptides. Identified defensins, owing to their small length and potent antimicrobial activity can be used effectively for development of new clinically applicable antibiotics. Thus predicting the defensin candidates will aid in accurate identification of novel peptide drugs. Support vector machines prediction model accuracy was 99% for defensin and defensin types. The results indicate that it is most accurate and efficient prediction method for defensin peptides. User friendly defensin web server is provided at www.defensinpred.cdac.in for the benefit of scientific community. PMID- 22670677 TI - Optimized soluble expression and purification of an aggregation-prone protein by fusion tag systems and on-column cleavage in Escherichia coli. AB - Previously we constructed a fusion protein based on GLP-1 and globular adiponectin but unfortunately its yield was low because it was mainly expressed as inclusion bodies. Herein to optimize the soluble expression of this fusion protein we tried several fusion tag systems. Fusion tags, including GST-, Trx- and MBP-tag, greatly improved the soluble expression of the fusion protein. However, these tag-fusion proteins were aggregation-prone as judged by Native PAGE and gel filtration chromatography, and this aggregation reduced the specificity of enterokinase-mediated enzyme cleavage which was essential to remove the fusion tags. To improve the specificity of protein cleavage, we employed on-column cleavage for downstream purification. Finally using optimized expression followed by on-column cleavage, we obtained the product fusion protein with a yield of 1.2 mg per g wet bacterial cells which was 8-fold higher than before. This method improved the yield and simplified the process, and as a convenient method it can also be used for the preparation of other aggregation prone proteins. PMID- 22670678 TI - High-resolution melting analysis allowed fast and accurate closed-tube genotyping of Fusarium oxysporum formae speciales complex. AB - The fungus Fusarium oxysporum is a highly complex species composed by many strains put together into groups called formae speciales. As it is difficult and laborious to discriminate Fusarium formae specials via biochemical or phenotypic methods, it is very important to develop novel, rapid, and simple to perform identification methods. Herein, real-time PCR assay [using universal internal transcribed spacer (ITS) primers] coupled with high-resolution melting (HRM) analysis was developed for identifying and distinguishing F. oxysporum formae speciales complex. The melting curve analysis of these amplicons specifically classified all isolates into seven F. oxysporum formae speciales and generated seven HRM curve profiles. The smallest DNA sequence difference recognized in this study was one nucleotide. The results presented show that HRM curve analysis of Fusarium ITS sequences is a simple, quick, and reproducible method that allows both the identification of seven F. oxysporum formae speciales and at the same time their screening for variants. Our genotyping assay uses the combined information of simultaneously acquired HRM data from an unlabeled probe and the full-length amplicon. Finally, the completion of both reaction and analysis in a closed tube saves time by eliminating the separate steps and reduces the risk of contamination. PMID- 22670679 TI - Feasibility and preliminary effectiveness of a novel mobility training intervention in infants and toddlers with cerebral palsy. AB - OBJECTIVE: To design a novel mobility training intervention incorporating infant motor learning and neurorehabilitation principles and investigate its feasibility, tolerability and effect on motor development in toddlers with cerebral palsy (CP). METHODS: A single-subject research design with repeated measures during 6-week baseline and intervention phases and after treatment withdrawal was used. Five participants attended therapy utilizing novel dynamic weight assistance technology, which allowed practice of motor skills beyond participants' current abilities. RESULTS: Average attendance and engagement rates exceeded 90%. Gains in gross motor function were observed after treatment that exceeded the expected rate in four of the five participants. Rates of motor development during treatment were 10.8, 3.8, 7.0, 15.1, and 0.3 times greater than during baseline for the five participants, respectively. CONCLUSIONS: This intervention was tolerated and demonstrated the potential to alter the trajectory of motor development in CP, providing proof of concept for further investigation. PMID- 22670680 TI - Copper(I)-catalyzed asymmetric desymmetrization: synthesis of five-membered-ring compounds containing all-carbon quaternary stereocenters. AB - A highly stereoselective catalytic alkylation sequence for the synthesis of highly functionalized and versatile five-membered-ring compounds bearing all carbon quaternary stereocenters was developed. Enantioselective desymmetrization of achiral cyclopentene-1,3-diones was thus executed by chiral Cu-phosphoramidite catalysts. A variety of complicated cyclopentane derivatives can be synthesized with excellent stereoselectivities using a low catalyst loading in a one-pot operation. PMID- 22670681 TI - Internet-using men who have sex with men would be interested in accessing authorised HIV self-tests available for purchase online. AB - Men who have sex with men (MSM) recruited in sex venues have been shown to be interested in accessing HIV home-tests if reliable and authorised tests were available. To what extent is this true for MSM recruited online? In an online survey in French on the use of unauthorised HIV home-tests purchased online, MSM previously unaware of the existence of these tests were asked if they would be interested in accessing them if these tests were authorised. Among 5908 non-HIV positive respondents, 86.5% expressed interest. Independent variables associated with interest included: being younger, living in smaller towns, having a job but not tertiary education and living in a conventional family with one's parents or a wife and family. Interested men were also more likely to have never done the standard HIV test or not in the last year, to have casual sex partners but on average not more than once a week, to take sexual risks with these partners, to live their sex-lives with men in absolute secrecy and yet often to try to make a date to see their sex partners again. Of the 5109 respondents interested in accessing self-tests purchasable online, 4362 (85.4%) answered an open question on their reasons for being interested. Using thematic analysis, principle themes identified proved to be similar to those found in earlier studies with MSM recruited in sex venues: convenience, rapidity accessing results and privacy. In answer to a closed question, men not interested chose as reasons: satisfaction with current method, doubts about reliability, not wanting to be alone when discovering results and fear of incorrect use. In conclusion, although the online questionnaire may have introduced selection bias over-representing men already interested, many Internet-using MSM are interested in accessing self-tests available for purchase online. PMID- 22670682 TI - Characterization of CD4+ cytotoxic lymphocytes and apoptosis markers induced by Trypanossoma cruzi infection. AB - Although the pathophysiology of Chagas disease is not completely understood, it is widely accepted that involvement of the immune response is critical in determining the outcome of the disease. In this context, CD4+ T cells may play an important role in generating different mechanisms of protection. In addition to effector and regulatory functions, CD4+ T cells may be also involved with lytic activities against the parasite and may have a relevant role on control of the infection. In this study, we have evaluated CD4+ T cells expressing cytotoxic and apoptosis markers in response to Trypanossoma cruzi infection in indeterminate (IND) and cardiac (CARD) patients with Chagas disease and non-infected individuals (NI). Our data demonstrated that: (1) CD4+ T cells presented higher ex vivo granzyme B expression in patients with Chagas disease compared with healthy individuals and that antigen induced a greater granzyme B expression in IND patients; (2) CD95L expression in CD4+ CD95+ T cells from IND patients is higher than in CARD and NI; (3) IND and CARD patients had an increased frequency of caspase-3 after in vitro stimulation and also expressed a high frequency of annexinV+ 7ADD+ within CD4+ T cells; (4) Lastly, a positive correlation was seen between cytotoxic molecules and CD45RO memory marker in CD4+ T cells and between caspase-3 and CD95L within CD4+ CD95+ T cells. These results suggest new insights into the functional competence of CD4+ T cells among the different clinical forms of Chagas disease, which will lead to a better understanding of their influence during immune responses against T. cruzi. PMID- 22670683 TI - Photochemical properties of mammalian melanopsin. AB - Melanopsin is the photoreceptor molecule of intrinsically photosensitive retinal ganglion cells, which serve as the input for various nonvisual behavior and physiological functions fundamental to organisms. The retina, therefore, possess a melanopsin-based nonvisual system in addition to the visual system based on the classical visual photoreceptor molecules. To elucidate the molecular properties of melanopsin, we have exogenously expressed mouse melanopsin in cultured cells. We were able to obtain large amounts of purified mouse melanopsin and conducted a comprehensive spectroscopic study of its photochemical properties. Melanopsin has an absorption maximum at 467 nm, and it converts to a meta intermediate having an absorption maximum at 476 nm. The melanopsin photoreaction is similar to that of squid rhodopsin, exhibiting bistability that results in a photosteady mixture of a resting state (melanopsin containing 11-cis-retinal) and an excited state (metamelanopsin containing all-trans-retinal) upon sustained irradiation. The absorption coefficient of melanopsin is 33000 +/- 1000 M(-1) cm(-1), and its quantum yield of isomerization is 0.52; these values are also typical of invertebrate bistable pigments. Thus, the nonvisual system in the retina relies on a type of photoreceptor molecule different from that of the visual system. Additionally, we found a new state of melanopsin, containing 7-cis-retinal (extramelanopsin), which forms readily upon long-wavelength irradiation (yellow to red light) and photoconverts to metamelanopsin with short-wavelength (blue light) irradiation. Although it is unclear whether extramelanopsin would have any physiological role, it could potentially allow wavelength-dependent regulation of melanopsin functions. PMID- 22670684 TI - Child temperament moderates effects of parent-child mutuality on self-regulation: a relationship-based path for emotionally negative infants. AB - This study examined infants' negative emotionality as moderating the effect of parent-child mutually responsive orientation (MRO) on children's self-regulation (n=102). Negative emotionality was observed in anger-eliciting episodes and in interactions with parents at 7 months. MRO was coded in naturalistic interactions at 15 months. Self-regulation was measured at 25 months in effortful control battery and as self-regulated compliance to parental requests and prohibitions. Negative emotionality moderated the effects of mother-child, but not father child, MRO. Highly negative infants were less self-regulated when they were in unresponsive relationships (low MRO), but more self-regulated when in responsive relationships (high MRO). For infants not prone to negative emotionality, there was no link between MRO and self-regulation. The "regions of significance" analysis supported the differential susceptibility model not the diathesis-stress model. PMID- 22670685 TI - Economic credentialing of physicians by insurance companies and headache medicine. PMID- 22670686 TI - Thermal transitions in dry and hydrated layer-by-layer assemblies exhibiting linear and exponential growth. AB - Layer-by-layer (LbL) assemblies are remarkable materials, known for their tunable mechanical, optical, and surface properties in nanoscale films. However, questions related to their thermal properties still remain unclear. Here, the thermal properties of a model LbL assembly of strong polyelectrolytes, poly(diallyldimethylammonium chloride)/poly(styrene sulfonate) (PDAC/PSS), assembled from solutions of varying ionic strength (0-1.25 M NaCl) are investigated using quartz crystal microbalance with dissipation (QCM-D) and modulated differential scanning calorimetry. Hydrated exponentially growing films (assembled from 0.25 to 1.25 M NaCl) exhibited distinct thermal transitions akin to a glass transition at 49-56 degrees C; linearly growing films (assembled without added salt) did not exhibit a transition in the temperature range investigated and were glassy. Results support the idea that exponentially growing films have greater segmental mobility than that of linearly growing films. On the other hand, all dry LbL assemblies investigated were glassy at room temperature and did not exhibit a T(g) up to 250 degrees C, independent of ionic strength. For the first time, thermal transitions such as T(g) values can be measured for LbL assemblies using QCM-D by monitoring fluctuations in changes in dissipation, allowing us to probe the film's internal structure as a function of film depth. PMID- 22670687 TI - Simvastatin exerts cardioprotective effects and inhibits the activity of Rho associated protein kinase in rats with metabolic syndrome. AB - 1. Insulin resistance (IR) is crucially involved in the pathophysiology of metabolic syndrome (MS). The aim of the present study was to investigate the effects of simvastatin on IR in rats with MS. 2. A rat model of MS was established and myocardial damage was examined by transmission electron microscopy. Twenty-two MS rats were divided into two groups of 11 rats each: (i) an MS group; and (ii) a simvastatin-treated MS. Ten Wistar rats were used as controls. The phosphorylation of myosin phosphatase target subunit 1 (MYPT-1), insulin receptor substrate 1 (IRS-1) and Akt were analysed by immunohistochemistry and western blotting. 3. Insulin resistance-induced MS was associated with a significant increase in Rho kinase (ROCK) activity and inhibition of the phosphatidylinositol 3-kinase (PI3-K)/Akt pathway. Decreased levels of phosphorylated (p-) MYPT-1 and p-IRS-1 (Ser307) and increased levels of p-Akt were found in hearts from the MS + simvastatin compared with the MS group. These results suggest that simvastatin reduces ROCK activity and increases Akt activity. 4. Simvastatin exerts cardioprotective effects and improves IR, which can be attributed, at least in part, to the inhibition of ROCK and activation of PI3-K/Akt. PMID- 22670688 TI - Rodent-borne hemorrhagic fevers: under-recognized, widely spread and preventable epidemiology, diagnostics and treatment. AB - This review presents an overview of the most important rodent-borne hemorrhagic fever pathogens directly transmitted from rodents to humans, namely Leptospira and hantaviruses, together with the New- and Old-World arenaviruses. These zoonotic diseases frequently share clinical symptoms, transmission routes and other epidemiological features and often have an emerging pattern. Differential diagnostics could benefit from a syndrome-based approach grouping these pathogens. In this review extensive descriptions of the epidemiology, clinical symptoms, diagnostics and treatment are provided including a practical overview, listing clinical features, diagnostics and risk factors for each selected rodent borne hemorrhagic fever pathogen. PMID- 22670689 TI - Feature binding and attention in working memory: a resolution of previous contradictory findings. AB - We aimed to resolve an apparent contradiction between previous experiments from different laboratories, using dual-task methodology to compare effects of a concurrent executive load on immediate recognition memory for colours or shapes of items or their colour-shape combinations. Results of two experiments confirmed previous evidence that an irrelevant attentional load interferes equally with memory for features and memory for feature bindings. Detailed analyses suggested that previous contradictory evidence arose from limitations in the way recognition memory was measured. The present findings are inconsistent with an earlier suggestion that feature binding takes place within a multimodal episodic buffer Baddeley, ( 2000 ) and support a subsequent account in which binding takes place automatically prior to information entering the episodic buffer Baddeley, Allen, & Hitch, ( 2011 ). Methodologically, the results suggest that different measures of recognition memory performance (A', d', corrected recognition) give a converging picture of main effects, but are less consistent in detecting interactions. We suggest that this limitation on the reliability of measuring recognition should be taken into account in future research so as to avoid problems of replication that turn out to be more apparent than real. PMID- 22670690 TI - Pushing the resolution limits in cryo electron tomography of biological structures. AB - Cryo electron tomography is a three-dimensional imaging technique that is suitable for imaging snapshots of the structural arrangements of biomolecular complexes and macromolecules, both in vitro and in the context of the cell. In terms of attainable resolution, cryo electron tomographic reconstructions now show resolvable details in the 5-10 nm range, connecting optical microscopy with molecular imaging techniques. In view of the current developments in super resolution light microscopy and correlative light and electron microscopy, cryo electron tomography will be increasingly important in structural biology as a tool to bridge light microscopy with molecular imaging techniques like NMR, X-ray diffraction and single particle electron microscopy. In cell biology, one goal, often referred to as visual proteomics, is the molecular mapping of whole cells. To achieve this goal and link cryo electron tomography to these high-resolution techniques, increasing the attainable resolution to 2-5 nm is vital. Here, we provide an overview of technical factors that limit the resolution in cryo electron tomography and discuss how during data acquisition and image processing these can be optimized to attain the highest possible resolution. Also, existing resolution measurement approaches and current technological developments that potentially increase the resolution in cryo electron tomography are discussed. PMID- 22670691 TI - Effect of long-term simulated microgravity on some sexual traits of male Japanese quail. AB - The aim of this study was to investigate the effects of long-term stay of Japanese quail in simulated microgravity on some sexual features of males. As a model for simulating microgravity exposure of birds in laboratory conditions was used hypodynamia. The mean left testis weight in males reared under hypodynamia from day 3 up to 180 days of age was lower than that of control (P<0.05), but the right testis weight differences between both groups were not significant. Also the area, volume and foam production of cloacal gland was not significantly decreased in hypodynamia birds at the end of experiment. By contrast, the plasma testosterone concentration of males living in hypodynamia was reduced about 50 % at 90 and 180 days of age in comparison to control (P<0.05) suggesting some negative effects on sexual development. Our results demonstrated that male quail kept under simulated microgravity conditions were sexually competent although their sexual efficiency was reduced especially in terms of plasma testosterone. PMID- 22670692 TI - Spectral peak frequency in low-frequency band in cross spectra of blood pressure and heart rate fluctuations in young type 1 diabetic patients. AB - In this study we tested whether joint evaluation of the frequency (f(cs)) at which maxima of power in the cross-spectra between the variability in systolic blood pressure and inter-beat intervals in the range of 0.06-0.12 Hz occur together with the quantification of baroreflex sensitivity (BRS) may improve early detection of autonomic dysfunction in type 1 diabetes mellitus (T1DM). We measured 14 T1DM patients (age 20.3-24.2 years, DM duration 10.4-14.2 years, without any signs of autonomic neuropathy) and 14 age-matched controls (Co). Finger arterial blood pressure was continuously recorded by Finapres for one hour. BRS and f(cs) were determined by the spectral method. Receiver-operating curves (ROC) were calculated for f(cs), BRS, and a combination of both factors determined as F(z)=1/(1+exp(-z)), z=3.09-0.013*BRS-0.027*f(cs). T1DM had significantly lower f(cs) than Co (T1DM: 88.8+/-6.7 vs. Co: 93.7+/-3.8 mHz; p<0.05), and a tendency towards lower BRS compared to Co (T1DM: 10.3+/-4.4 vs. Co: 14.6+/-7.1 ms/mm Hg; p=0.06). The ROC for Fz showed the highest sensitivity and specificity (71.4 % and 71.4 %) in comparison with BRS (64.3 % and 71.4 %) or f(cs) (64.3 % and 64.3 %). The presented method of evaluation of BRS and f(cs) forming an integrated factor Fz could provide further improvement in the risk stratification of diabetic patients. PMID- 22670693 TI - The mechanisms of inhibition of frog endplate currents with homologous derivatives of the 1,1-dimethyl-3-oxybutyl phosphonic acid. AB - The mode of inhibition of endplate currents by four esters of 1,1-dimethyl-3 oxybutyl phosphonic acid with different lipophilicities and molecule lengths were estimated by mathematical modeling based on previous electrophysiological data supplemented by several experiments with rhythmic stimulation. The aim was to discriminate between their receptor and non-receptor effects. It was shown that all esters have a two-component mechanism of depression: inhibition of the receptor open channel and allosteric modulation of the receptor-channel complex. The ratio of both functional components depends on the length and lipophilicity of the esters. Short and less lipophilic esters mostly act as open channel inhibitors and the rate of inhibition substantially depends on the rate of stimulation, i. e. probability of the receptor-channel opening. As the length of the ester radicals and their lipophilicity increased, these compounds were more active as allosteric receptor inhibitors, probably hindering the function of nAChRs from the lipid annulus. PMID- 22670694 TI - Metabolism of dehydroepiandrosterone sulfate and estrone-sulfate by human platelets. AB - The aim of the present research was to study the uptake of DHEAS, and to establish the intracrine capacity of human platelets to produce sex steroid hormones. The DHEAS transport was evaluated through the uptake of [(3)H]-DHEAS in the presence or absence of different substrates through the organic anion transporting polypeptide (OATP) family. The activity of sulfatase enzyme was evaluated, and the metabolism of DHEAS was measured by the conversion of [(3)H] DHEAS to [(3)H]-androstenedione, [(3)H]-testosterone, [(3)H]-estrone and [(3)H] 17beta-estradiol. Results indicated the existence in the plasma membrane of an OATP with high affinity for DHEAS and estrone sulphate (E(1)S). The platelets showed the capacity to convert DHEAS to active DHEA by the steroid-sulfatase activity. The cells resulted to be a potential site for androgens production, since they have the capacity to produce androstenedione and testosterone; in addition, they reduced [(3)H]-estrone to [(3)H]-17beta-estradiol. This is the first demonstration that human platelets are able to import DHEAS and E(1)S using the OATP family and to convert DHEAS to active DHEA, and to transform E(1)S to 17beta-estradiol. PMID- 22670695 TI - Coupled nitric oxide and autonomic receptor functional responses in the normal and inflamed urinary bladder of the rat. AB - Both divisions of the autonomic nervous system are involved in regulation of urinary bladder function. Several substances, other than noradrenaline and acetylcholine, seem to play important roles in physiology and pathophysiology of lower urinary tract. In the current study, we aimed to examine if there exist interplays between nitric oxide (NO) and autonomic transmitters and if such interactions vary in different parts of the urinary bladder in healthy and cyclophosphamide (CYP)-induced cystitic rats; when administered to the animals (100 mg/kg; i.p.), the cytotoxic CYP metabolite acrolein induces bladder inflammation. In the current study a series of in vitro functional studies were performed on detrusor muscle strip preparations. Stimulation with electrical field stimulation (EFS), methacholine, adenosine 5'-triphosphate (ATP), and adrenaline evoked contractile responses in isolated bladder preparations that were significantly reduced in cyclophosphamide (CYP)-treated rats. While the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine (L-NNA; 10(-4) M) did not affect contractile responses in normal, healthy strip preparations, it significantly increased the contractile responses to EFS, methacholine and adrenaline, but not to ATP, in the bladders from the CYP-treated rats. In the CYP treated rats, the ATP-evoked relaxatory part of its dual response (an initial contraction followed by a relaxation) was 6-fold increased in comparison with that of normal preparations, whereas the isoprenaline relaxation was halved in the CYP-treated. While L-NNA (10(-4) M) had no effect on the isoprenaline-evoked relaxations, it reduced the ATP-evoked relaxations in strip preparations from the bladder body of CYP-treated rats. Stimulation of beta(2)- and beta(3) adrenoceptors evoked relaxations and both responses were reduced in cystitis, the latter to a larger extent. In the trigone, the reduced ATP-evoked contractile response in the inflamed strips was increased by L-NNA, while L-NNA had no effect on the ATP-evoked relaxations, neither on the relaxations in healthy nor on the larger relaxations in the inflamed trigone. The study shows that both contractile and relaxatory functions are altered in the state of inflammation. The parasympathetic nerve-mediated contractions of the body of the bladder, evoked by the release of ATP and acetylcholine, were substantially reduced in cystitis. The relaxations to beta-adrenoceptor and purinoceptor stimulation were also reduced but only the ATP-evoked relaxation involved NO. PMID- 22670696 TI - Nitrotyrosine and nitrate/nitrite levels in cardiac arrest survivors treated with endovascular hypothermia. AB - The protective effect of therapeutic hypothermia in cardiac arrest survivors (CAS) has been previously well documented. Animal studies have indicated that attenuation of tissue oxidative stress (OS) may be involved in the mechanisms that lead to the beneficial effect of hypothermia. The extent of OS and nitric oxide (NO) production in adult CAS treated with endovascular hypothermia is, however, unknown. A total of 11 adult patients who experienced cardiac arrest out of hospital were included in the present study, and all were treated with mild hypothermia using the Thermogard XP (Alsius, USA) endovascular system. A target core temperature of 33 degrees C was maintained for 24 hours, with a subsequent rewarming rate of 0.15 degrees C per hour, followed by normothermia at 36.8 degrees C. Blood samples for the measurement of nitrotyrosine and nitrate/nitrite levels were drawn at admission and every 6 hours thereafter for two days. During the hypothermic period, the levels of nitrotyrosine and nitrates/nitrites were comparable with baseline values. During the rewarming period, serum levels of both parameters gradually increased and, during the normothermic period, the levels were significantly higher compared with hypothermic levels (nitrotyrosine, P<0.001; nitrates/nitrites, P<0.05). In our study, significantly lower levels of nitrotyrosine and nitrates/nitrites were demonstrated during hypothermia compared with levels during the normothermic period in adult CAS. These data suggest that attenuation of OS and NO production may be involved in the protective effect of hypothermia in adult CAS. PMID- 22670697 TI - Wnt/beta-catenin signaling: a promising new target for fibrosis diseases. AB - Wnt/beta-catenin signaling is involved in virtually every aspect of embryonic development and also controls homeostatic self-renewal in a number of adult tissues. Recently, emerging evidence from researches of organ fibrosis suggest that sustained Wnt/beta-catenin pathway reactivation is linked to the pathogenesis of fibrotic disorders. Here we focus on Wnt/beta-catenin-related pathogenic effects in different organs, such as lung fibrosis, liver fibrosis, skin fibrosis and renal fibrosis. Additionally, Wnt/beta-catenin signaling works in a combinatorial manner with TGF-beta signaling in the process of fibrosis, and TGF-beta signaling can induce expression of Wnt/beta-catenin superfamily members and vice versa. Moreover, network analysis, based on pathway databases, revealed that key factors in the Wnt pathway were targeted by some differentially expressed microRNAs detected in fibrosis diseases. These findings demonstrated the crosstalks between Wnt/beta-catenin pathway and TGF-beta signalings, and microRNAs, highlighting the role of Wnts in organ fibrogenesis. Most importantly, nowadays there is a variety of Wnt pathway inhibitors which give us the potential therapeutic feasibility, modulation of the Wnt pathway may, therefore, present as a suitable and promising therapeutic strategy in the future. PMID- 22670698 TI - The effect of diabetes mellitus on the ventricular epicardial activation and repolarization in mice. AB - Cardiac repolarization is prolonged in diabetes mellitus (DM), however the distribution of repolarization durations in diabetic hearts is unknown. We estimated the ventricular repolarization pattern and its relation to the ECG phenomena in diabetic mice. Potential mapping was performed on the anterior ventricular surface in healthy (n=18) and alloxan-induced diabetic (n=12) mice with the 64-electrode array. Activation times, end of repolarization times, and activation-recovery intervals (ARIs) were recorded along with limb lead ECGs. ARIs were shorter in the left as compared to right ventricular leads (P<0.05). The global dispersion of repolarization, interventricular and apicobasal repolarization gradients were greater in DM than in healthy animals (P<0.03). The increased dispersion of repolarization and apicobasal repolarization gradient in DM correlated with the prolonged QTc and Tpeak-Tend intervals, respectively. The increased ventricular repolarization heterogeneity corresponded to the electrocardiographic markers was demonstrated in DM. PMID- 22670699 TI - Effects of isoflurane concentration on basic echocardiographic parameters of the left ventricle in rats. AB - Transthoracic echocardiography (TTE) has become an important modality for the assessment of cardiac structure and function in animal experiments. The acquisition of echocardiographic images in rats requires sedation/anesthesia to keep the rats immobile. Commonly used anesthetic regimens include intraperitoneal or inhalational application of various anesthetics. Several studies have compared the effects of anesthetic agents on echocardiographic parameters in rats; however, none of them examined the effects of different concentrations of inhalational anesthetics on echocardiographic parameters. Accordingly, the aim of this study was to examine the effects of different concentrations of isoflurane used for anesthesia during TTE examination in rats on basic echocardiographic parameters of left ventricular (LV) anatomy and systolic function. TTE examinations were performed in adult male Wistar rats (n=10) anesthetized with isoflurane at concentrations of 1.5-3 %. Standard echocardiograms were recorded for off-line analysis. An absence of changes in basic echocardiographic parameters of LV anatomy and systolic function was found under isoflurane anesthesia using concentrations between 1.5-2.5 %. An isoflurane concentration of 3 % caused a small, but statistically significant, increase in LV chamber dimensions without a concomitant change in heart rate or fractional shortening. For the purpose of TTE examination in the rat, our results suggest that isoflurane concentrations = 2 cm in length. METHODS: Patients with columnar-lined oesophagus >= 2 cm in length and no intestinal metaplasia in biopsy specimens from two consecutive endoscopies with at least a 1-year interval were prospectively followed. A cohort of Barrett's oesophagus patients was used as a control. RESULTS: Columnar-lined oesophagus without intestinal metaplasia (n = 15) had a similar gender distribution, reflux symptoms prevalence and length as those of Barrett's oesophagus (n = 205). Patients were significantly younger (28.6 vs. 60 years, P < 0.0001) and accounted for 48% of patients aged <40 years in the two cohorts, but only 1% of those aged >40 years (P < 0.001). Patient distribution in both cohorts in 5 age brackets (0 19, 20-29, 30-39, 40-49, and >50 years) was significantly different, except for patients aged 40-49 years. Intestinal metaplasia was documented in 60% of the cohort after a mean follow-up of 7.1 years. CONCLUSIONS: Columnar-lined oesophagus without intestinal metaplasia >= 2 cm is infrequent in the setting of a systematic biopsy protocol, is associated with a younger age in comparison with Barrett's oesophagus, and appears to be an intermediate step between squamous and intestinal lining of the oesophagus. PMID- 22670706 TI - Immunoglobulin G dimers and immune complexes are dispensable for the therapeutic efficacy of intravenous immune globulin in murine immune thrombocytopenia. AB - BACKGROUND: Several mechanisms have been proposed to explain the therapeutic effects of intravenous immunoglobulin (IVIG) in immune thrombocytopenia (ITP). Noteworthy, a major role has been attributed to immunoglobulin (Ig)G dimers present in IVIG. It has also been suggested that immune complexes formed between IVIG and the patient's proteins after infusion could contribute to the therapeutic effect of IVIG in several autoimmune disorders. We recently observed that in-house preparations of polyclonal human IgG derived from small pools of plasma and devoid of IgG dimers were as efficient as IVIG in a mouse model of thrombocytopenia. In this work, we revisited the role of IgG dimers in the therapeutic effects of IVIG in ITP. STUDY DESIGN AND METHODS: We used the passive mouse model of ITP to determine the therapeutic efficacy of human IgG preparations devoid of IgG dimers and of dimer-enriched and -depleted commercial IVIG. Immune complex formation between IVIG and mouse plasma proteins was evaluated using a combination of chromatography and immunoprecipitation procedures. RESULTS: All preparations tested showed the same efficacy to alleviate ITP, regardless of their dimer contents. Significant amounts of immune complexes formed between IVIG and mouse plasma proteins were detected. However, the amount of immune complexes detected using the in-house preparation of human polyclonal IgG and mouse plasma was significantly lower, although the in-house preparation exhibited the same therapeutic efficacy as commercial IVIG. CONCLUSION: IgG dimers and immune complexes are dispensable to prevent thrombocytopenia in a mouse model of the disease. PMID- 22670707 TI - Knowledge of HIV transmission through breast milk among drug-dependent pregnant women. AB - Abstract The current study examined the correlates of knowledge about human immunodeficiency virus (HIV) transmission through breast milk among drug dependent pregnant women. There is a tremendous need to examine the knowledge about HIV transmission through breastfeeding among this largely understudied, but high-risk subset of pregnant women in order to minimize the extent to which they pass HIV to their children after giving birth. Participants included 97 pregnant women from Baltimore, MD, USA. Prevalence of drug use over the last 6 months included 37.1% reporting smoking marijuana, 36.1% injecting heroin, and 67.0% smoking crack. When asked whether HIV could be transmitted through breast milk, 72 women (74.2%) answered correctly. Our results indicate that the overall knowledge about transmission through breast milk is relatively low. Furthermore, participants who smoked crack during the past 6 months and participants who were white were significantly less likely to have correct knowledge about this topic. Our findings have important implications with regard to preventive interventions for this population. Future research is needed to determine how to best modify these interventions to address the specific needs of drug-dependent pregnant women, and how to specifically target white women and women who smoke crack. PMID- 22670708 TI - Methicillin-resistant Staphylococcus aureus burden in nursing homes associated with environmental contamination of common areas. AB - OBJECTIVES: To determine whether environmental cleaning and contamination are associated with variation in the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) between nursing homes. DESIGN: Prospective study of environmental contamination and cleaning quality. SETTING: Nursing home. PARTICIPANTS: Ten California nursing homes. MEASUREMENTS: Nursing homes were categorized into two groups based upon high and low differences in MRSA point prevalence and admission prevalence (delta prevalence) from nares screenings of nursing home residents. Environmental cleaning and infection control practices were evaluated by culturing common area objects for MRSA, assessing removal of intentionally applied marks visible only under ultraviolet (UV) light, and administering surveys on infection control and cleaning. RESULTS: Overall, 16% (78/500) of objects were MRSA positive, and 22% (129/577) of UV-visible marks were removed. A higher proportion of MRSA-positive objects was found in the high (19%) than in low (10%) nursing home groups (P = .005). Infection control and cleaning policies varied, including the frequency of common room cleaning (median 2.5 times daily, range 1-3 times daily) and time spent cleaning per room (median 18 minutes, range 7-45 minutes). In multivariate models, MRSA-positive objects were associated with high delta prevalence nursing homes (odds ratio (OR) = 2.8, P = .005), less time spent cleaning each room (OR = 2.9, P < .001), and less frequent cleaning of common rooms (OR = 1.5, P = .01). CONCLUSION: Substantial variation was found in MRSA environmental contamination, infection control practices, and cleaning quality. MRSA environmental contamination was associated with greater differences between MRSA point and admission prevalence, less frequent common room cleaning, and less time spent cleaning per room, which suggests that modifying cleaning practices may reduce MRSA environmental contamination and burden in nursing homes. PMID- 22670709 TI - Activation of AMPK by pterostilbene suppresses lipogenesis and cell-cycle progression in p53 positive and negative human prostate cancer cells. AB - Prostate cancer is one of the leading causes of cancer death in men in Western countries. Epidemiological studies have linked the consumption of fruits and vegetables to a reduced risk of prostate cancer, and small fruits are particularly rich sources of many active phytochemical stilbenes, such as pterostilbene. As a constituent of small fruits such as grapes, berries, and their products, pterostilbene is under intense investigation as a cancer chemopreventive agent. Using the p53 wild type LNCaP and p53 null PC3 cells, we found that treatment with pterostilbene resulted in dose-dependent inhibition of cellular proliferation, which suggested that the interaction of pterostilbene with the p53 might not fully explain its inhibitory effect on proliferation. In this study, we found that pterostilbene activated AMPK in both p53 positive and negative human prostate cancer cells. Pterostilbene-activated AMPK decreased the activity and/or expression of lipogenic enzymes, such as fatty acid synthase (FASN) and acetyl-CoA carboxylase (ACC). Interestingly, the resolution between apoptosis and growth arrest following AMPK activation is greatly influenced by p53 status. In p53 positive LNCaP cells, pterostilbene blocked the progression of cell cycle at G1 phase by inducing p53 expression and further up-regulating p21 expression. However, pterostilbene induced apoptosis in p53 negative PC3 cells. Our results suggest that pterostilbene may be a functional chemopreventive agent and that dietary exposure to pterostilbene would be helpful for antiprostate cancer activity. PMID- 22670711 TI - Total synthesis and structural revision of hericerin. AB - The total synthesis of hericerin, a pollen growth inhibitor from Hericium erinaceum, was achieved. We found that the reported structure of hericerin should be revised to be the carbonyl regioisomer. PMID- 22670710 TI - Evaluation of lithium response in episodic cluster headache: a retrospective case series. AB - OBJECTIVE: In this study, we attempted to evaluate the response to lithium treatment and its tolerability in the prevention of episodic cluster headache (CH) and to identify clinical predictors of response. BACKGROUND: Verapamil and lithium are the most widely used drugs in the prevention of CH attacks. Lithium is considered a second-line treatment in part because of its potentially severe adverse drug reactions (ADRs). Evidence for the efficacy of lithium in CH prevention is greater in chronic than in episodic patients. In addition, because of its narrow therapeutic window and ADRs (which can be significantly reduced with proper periodical monitoring of blood levels), lithium is recommended only in chronic CH, when other drugs are ineffective or potentially harmful. METHODS: Our primary aim was to determine whether lithium reduced the number of attacks per day (attack frequency). We compared attack frequency in 3 periods: run-in, the first, and the second week of lithium treatment. Responders were defined as patients showing at least a 50% reduction in attack frequency. RESULTS: Lithium response was evaluated in 26 patients. Treatment led to a significant reduction in attack frequency within 2 weeks in a percentage of 77% of responders and 23% of nonresponders. Responders and nonresponders did not differ in terms of demographic and clinical characteristics. Only 15% of patients experienced mild ADRs. CONCLUSION: Our study provides additional evidence on the effectiveness of lithium in the prevention of episodic CH. It also shows the tolerability of lithium, given the short duration of treatment and low dosage. PMID- 22670713 TI - Two pathways for the formation of ethylene in CO reduction on single-crystal copper electrodes. AB - Carbon monoxide is a key intermediate in the electrochemical reduction of carbon dioxide to methane and ethylene on copper electrodes. We investigated the electrochemical reduction of CO on two single-crystal copper electrodes and observed two different reaction mechanisms for ethylene formation: one pathway has a common intermediate with the formation of methane and takes place preferentially at (111) facets or steps, and the other pathway involves selective reduction of CO to ethylene at relatively low overpotentials at (100) facets. The (100) facets seem to be the dominant crystal facets in polycrystalline copper, opening up new routes to affordable (photo)electrochemical production of hydrocarbons from CO(2). PMID- 22670712 TI - Identification and proteome analysis of the two-component VirR/VirS system in epidemic Streptococcus suis serotype 2. AB - Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen that infects pigs and sporadically causes serious infections in humans. Two recent large-scale outbreaks of human streptococcal toxic-shock-like syndrome with high mortality occurred in China, posing new challenges for global public health. However, the global regulation of the virulence of epidemic SS2 isolates lacks a systematic understanding. In this study, we performed a mutational and functional analysis of an SS2 two-component system that is orthologous to the VirR/VirS regulatory system of Clostridium perfringens. An isogenic knockout mutant of VirR/VirS (DeltavirRS) was found to exhibit marked phenotypic changes, including the formation of shorter chains and thinner capsular walls, more easily cleared in whole blood, and decreased oxidative stress tolerance. Furthermore, the DeltavirRS mutant was greatly attenuated in a mouse model. Comparative proteome analysis of the expression profiles of the wild-type strain with the DeltavirRS mutant allowed us to identify 72 proteins that are differentially expressed in the absence of the VirR/VirS system and that are directly responsible for the pleiotropic phenotype of the DeltavirRS mutant. PMID- 22670714 TI - Tailored design of architecturally controlled Pt nanoparticles with huge surface areas toward superior unsupported Pt electrocatalysts. AB - Herein, we report a very simple and rapid method to synthesize two types of Pt nanoparticles with open porous structures (i.e., Pt nanodendrites and multiarmed Pt nanostars) in high yield. The present synthesis is performed by a simple sonication treatment of an aqueous solution containing K2PtCl4 and a nonionic block copolymer with branched alkyl chains in the presence of ascorbic acid (AA) at room temperature. Nanodendrites and multiarmed nanostars with different Pt nanostructures are selectively synthesized by simply controlling the dissolved block copolymer amounts in the reactive system. As-prepared 3D Pt nanodendrites and multiarmed Pt nanostars with well-defined morphologies are highly porous and self-supported structures assembled by staggered nanoarms as building blocks, thereby realizing extremely high surface areas (around 80 m(2) g(-1)). The present synthesis has a remarkable advantage in its simplicity for the synthesis of Pt nanocatalysts, in comparison with other previous approaches. Our Pt nanodendrites and Pt nanostars not only improve the active Pt surface area but also show superior electrochemical performance, which make them promising electrocatalysts for future. PMID- 22670715 TI - Structural insights into the interaction between the bacterial flagellar motor proteins FliF and FliG. AB - The binding of the soluble cytoplasmic protein FliG to the transmembrane protein FliF is one of the first interactions in the assembly of the bacterial flagellum. Once established, this interaction is integral in keeping the flagellar cytoplasmic ring, responsible for both transmission of torque and control of the rotational direction of the flagellum, anchored to the central transmembrane ring on which the flagellum is assembled. Here we isolate and characterize the interaction between the N-terminal domain of Thermotoga maritima FliG (FliG(N)) and peptides corresponding to the conserved C-terminal portion of T. maritima FliF. Using nuclear magnetic resonance (NMR) and other techniques, we show that the last ~40 amino acids of FliF (FliF(C)) interact strongly (upper bound K(d) in the low nanomolar range) with FliG(N). The formation of this complex causes extensive conformational changes in FliG(N). We find that T. maritima FliG(N) is homodimeric in the absence of the FliF(C) peptide but forms a heterodimeric complex with the peptide, and we show that this same change in oligomeric state occurs in full-length T. maritima FliG, as well. We relate previously observed phenotypic effects of FliF(C) mutations to our direct observation of binding. Lastly, on the basis of NMR data, we propose that the primary interaction site for FliF(C) is located on a conserved hydrophobic patch centered along helix 1 of FliG(N). These results provide new detailed information about the bacterial flagellar motor and support efforts to understand the cytoplasmic ring's precise molecular structure and mechanism of rotational switching. PMID- 22670716 TI - SOCS1 gene expression is increased in severe pulmonary tuberculosis. AB - Suppressors of cytokine signalling (SOCS) molecules inhibit cytokine signalling and may regulate protective immunity in tuberculosis (TB). We investigated the association of SOCS with disease progression in patients with pulmonary TB. For this purpose, we studied peripheral blood mononuclear cells (PBMCs) and T cells from patients with pulmonary TB (TB, n=33) and healthy endemic controls (EC, n=15). Cases were stratified into those with moderately advanced (Mod-PTB) or far advanced disease (Adv-PTB). Interferon-gamma (IFN-gamma), SOCS1 and SOCS3 gene expression was determined by RT-PCR. Statistical analysis was performed using the Mann-Whitney test. Levels of IL6 (P=0.018) and IL10 (P=0.013) were found to be elevated in PBMC supernatants from patients with TB as compared with EC. SOCS1 mRNA gene expression in T cells from patients with TB was increased as compared with that of EC (P=0.02). In addition, levels of SOCS1 mRNA transcripts were found to be elevated in PBMCs of Adv-PTB as compared with Mod-PTB (P=0.008) cases. Our data show that raised SOCS1 levels are associated with increased disease severity in TB. As SOCS1 regulates IFN-gamma-driven immunity and SOCS1 can be further upregulated by IL6 levels, the increase in SOCS1 in severe disease indicates a mechanism by which mycobacteria impede disease control in TB. PMID- 22670717 TI - Children's use of analogy during collaborative reasoning. AB - This microgenetic study examined social influences on children's development of analogical reasoning during peer-led small-group discussions of stories about controversial issues. A total of 277 analogies were identified among 7,215 child turns for speaking during 54 discussions from 18 discussion groups in 6 fourth grade classrooms (N = 120; age M=10.0, SD=0.6). Use of analogy was found to spread among the children in discussion groups and occur at an accelerating rate, primarily because of the increasing use of novel analogies. Relational analogies with shared surface features triggered purely relational analogies during the next 2 speaking turns, showing a trend of relational shift. These results provide distinctive new evidence for the importance of social interaction in an aspect of cognitive development. PMID- 22670718 TI - Endonucleolytic inhibition assay of DNA/Fok I transducer as a sensitive platform for homogeneous fluorescence detection of small molecule-protein interactions. AB - This paper reported a novel homogeneous fluorescence assay strategy for probing small molecule-protein interactions based on endonucleolytic inhibition of a DNA/Fok I transducer. The transducer could cyclically cleave fluorescence quenched probes to yield activated fluorescence signal, while protein binding to the small molecule label would prevent Fok I from approaching and cleaving the fluorescence-quenched probes. Because of the efficient signal amplification from the cyclic cleavage operation, the developed strategy could offer high sensitivity for detecting small molecule-protein interactions. This strategy was demonstrated using folate and its high-affinity or low-affinity binding proteins. The results revealed that the developed strategy was highly sensitive for detecting either high- or low-affinity small molecule-protein interactions with improved selectivity against nonspecific protein adsorption. This strategy could also be extended for assays of candidate small-molecule ligands using a competitive assay format. Moreover, this strategy only required labeling the small molecule on a DNA heteroduplex, circumventing protein modifications that might be harmful for activity. In view of these advantages, this new method could have potential to become a universal, sensitive, and selective platform for quantitative assays of small molecule-protein interactions. PMID- 22670719 TI - The effects of slip velocity on a micropolar fluid through a porous channel with expanding or contracting walls. AB - In this paper, a simple mathematical model depicting blood flow in the deforming porous channel is developed with an emphasis on the permeability property of the blood vessel and slip boundary based on Beavers and Joseph slip condition. In this study, the blood is represented by a micropolar fluid. With such an ideal model, the governing equations are reduced to ordinary ones by introducing suitable similar transformations. Homotopy analysis method is employed to obtain the expressions for velocity and microrotation fields. Graphs are sketched for some values of parameters such as slip coefficient and expansion ratio, and the associated dynamic characteristics are analysed in detail. PMID- 22670720 TI - The importance of bidirectional block during pulmonary vein isolation. AB - The definition of a successful ablation of atrial fibrillation can vary among electrophysiologists. A commonly described endpoint is bidirectional block of the four pulmonary veins. A case is described in which entrance block into a pulmonary vein was achieved early during pulmonary vein isolation. However, triggers from the pulmonary vein continued to conduct into the atrium, revealing the block was only unidirectional. Further ablation resulted in true electrical isolation and highlights the importance of achieving bidirectional block. PMID- 22670721 TI - Physicochemical and microbiological stability studies of extemporaneous antihypertensive pediatric suspensions for hospital use. AB - Extemporaneous suspensions of the antihypertensive agents furosemide, spironolactone and hydrochlorothiazide for pediatric use have been prepared at University Hospital (Federal University of Santa Catarina - Brazil). The aim of this work was to investigate the physicochemical and microbiological stability of these suspensions over the estimated shelf-life period of seven days and, if necessary, to optimize the formulations by improving the chemical stability. The pediatric suspensions were prepared using drug raw material and were stored at 25 +/- 2 degrees C and 5 +/- 3 degrees C. Chemical stability was evaluated by HPLC assay of the suspensions for drug content. Physical stability was evaluated by sedimentation volume, redispersibility, particle size, and zeta potential. Viable bacterial and fungal contaminations were assessed according to the official compendium. Furosemide and spironolactone suspensions as prepared herein can be stored for 7 days. However, the hydrochlorothiazide suspension formulation at pH 6.5 demonstrated poor chemical stability and was optimized by adjusting the pH to 3.3 where the drug exhibited acceptable stability. The optimized formulation demonstrated to be stable over the required period of 7 days. PMID- 22670722 TI - Drugs that inhibit gastric acid secretion may alter the course of inflammatory bowel disease. AB - BACKGROUND: Recent data suggest that acid suppressive medications may alter factors central to the pathophysiology of inflammatory bowel diseases (IBD), whether through shifts in the intestinal microbiome due to acid suppression or effects on immune function. AIM: To assess the relationship between the use of proton pump inhibitors (PPIs) or histamine2-receptor antagonists (H2Ra) and incidence of 'flares' (hospitalisation/surgery and change in medication). METHODS: We conducted a new user cohort study including individuals diagnosed with IBD in British Columbia using linked healthcare utilisation databases (available from July 1996 through April 2006). Propensity-score matched incidence rates during a 6-month follow-up period and rate ratios (RR) and 95% CI were calculated. RESULTS: Among 16 151 IBD patients, 1307 Crohn's disease (CD) and 996 ulcerative colitis (UC) patients experienced a new use of PPIs, whereas 741 CD and 738 UC used H2Ra. All IBD subgroups were matched separately to an equal number of unexposed IBD patients. H2Ra use in CD doubled the risk of hospitalisation/surgery (RR = 1.94; 95%CI 1.24-3.10) and numerically less so in UC patients (RR = 1.11) with widely overlapping CIs (0.61-2.03). Proton pump inhibitors use was associated with medication change in UC (RR = 1.39; 95%CI 1.20 1.62), but without meaningfully, increased risk of hospitalisation/surgery for UC or CD patients. Extending follow-up showed persistence, but attenuation, of all effects. CONCLUSIONS: Initiation of PPIs or H2Ra may be associated with short term changes in the course of IBD. Although confounding by indication was adjusted using propensity score matching, residual confounding may persist and findings need to be interpreted cautiously. PMID- 22670723 TI - Physical self-similarity enhances the gaze-cueing effect. AB - Important social information can be gathered from the direction of another person's gaze, such as their intentions and aspects of the environment that are relevant to those intentions. Previous work has examined the effect of gaze on attention through the gaze-cueing effect: an enhancement of performance in detecting targets that appear where another person is looking. The present study investigated whether the physical self-similarity of a face could increase its impact on attention. Self-similarity was manipulated by morphing participants' faces with those of strangers. The effect of gaze direction on target detection was strongest for faces morphed with the participant's face. The results support previous work suggesting that self-similar faces are processed differently from dissimilar faces. The data also demonstrate that a face's similarity to one's own face influences the degree to which that face guides our attention in the environment. PMID- 22670725 TI - Application of the self-generation effect to the learning of Blissymbols by persons presenting with a severe aphasia. AB - This study investigated the application of the self-generation effect to enhance the recognition and retention of Blissymbols in persons with severe aphasia. A 2*2*3 factorial design of two treatment types (self-generation and non generation) was used to teach two sets of Blissymbols. These were administered during 3 training days, between which were withdrawal periods of 1 day and 7 days. Recognition and retention probes were administered at intervals during the training. ANOVA analysis showed that the self-generation treatment produced no immediate recognition advantage; however, better retention of symbol recognition may have occurred over time. Hence, the potential application of the self generation effect in enhancing the retention of Blissymbols in persons with severe aphasia may warrant further investigation. PMID- 22670726 TI - Factors affecting computer mouse use for young children: implications for AAC. AB - More than 12% of preschoolers receiving special education services have complex communication needs, including increasing numbers of children who do not have significant motor impairments (e.g., children with autism spectrum disorders, Down syndrome, etc.). In order to meet their diverse communication needs (e.g., face-to-face, written, Internet, telecommunication), these children may use mainstream technologies accessed via the mouse, yet little is known about factors that affect the mouse performance of young children. This study used a mixed factorial design to investigate the effects of age, target size, and angle of approach on accuracy and time required for accurate target selection with a mouse for 20 3-year-old and 20 4-year-old children. The 4-year-olds were generally more accurate and faster than the 3-year-olds. Target size and angle mediated differences in performance within age groups. The 3-year-olds were more accurate and faster in selecting the medium and large targets relative to the small target, were faster in selecting the large relative to the medium target, and were faster in selecting targets along the vertical relative to the diagonal angle. The 4-year-olds were faster in selecting the medium and large targets relative to the small target. Implications for improving access to AAC include the preliminary suggestion of age-related threshold target sizes that support sufficient accuracy, the possibility of efficiency benefits when target size is increased up to an age-related threshold, and identification of the potential utility of the vertical angle as a context for training navigational input device use. PMID- 22670727 TI - Performance of children with typical development when reading and interpreting graphic-symbol sequences. AB - In order to understand a sequence of graphic symbols as sentences, one must not only recognize the meaning of individual symbols but also integrate their meaning together. In this study children without disabilities were asked to perform two tasks that presented sequences of graphics as stimuli but that differed in the need to treat the symbols as a sentence (i.e., with evidence of relationships among the individual symbols): a "reading" task (transpose the symbol sequence into speech), and an act-out task (demonstrate the meaning of the symbol sequences using puppets). The participants, aged 3 (n=18), 4 (n=36), 5 (n=27), and 6 (n=23) years, all succeeded on the reading task, but the younger groups were much less successful than the older groups on the act-out task. The children were more likely to pass the act-out task if they used conjugated rather than infinitive verb forms in their spoken responses on the reading task. In the younger age groups, children who used conjugated verb forms had higher receptive vocabulary scores. The findings suggest that being able to reproduce a sequence of symbols does not guarantee that the symbols are treated as a sentence. The inclusion in the study of children who were able to respond using speech, permitted observation of two types of responses (conjugated versus infinitive verb forms) that revealed different levels of understanding of graphic symbol sequences. PMID- 22670728 TI - Family influences and academic success: the perceptions of individuals using AAC. AB - Positive family influences have a significant impact on addressing school barriers to academic success for students from socially disadvantaged backgrounds. Due to inequities and attitudes toward people with complex communication needs, positive family influences may be critical in the academic success of students using AAC. This study asked the following question of eight United States high school graduates who have used augmentative and alternative communication (AAC): How do family influences positively affect the ability of students who use AAC to succeed in the secondary academic environment? Five themes emerged from the qualitative analysis of participants' narratives: (a) the impact of the family in seeking appropriate education, (b) homework as a challenge that was made easier through the involvement of the family, (c) the role of the family in communicating the importance of education, (d) mothers as driving forces of support, and (e) family encouragement for self-determination. This research allows families and schools to recognize the needs of students and to take action to meet them. It identifies the needs of families and schools in establishing relationships with each other, in terms of supporting requirements for accommodation, learning, motivation, and self-determination of students with complex commmunication needs. PMID- 22670729 TI - Perceptions of communication style and influences on intervention practices for young children with AAC needs. AB - The current study was designed to determine whether SLP perceptions of communication style (passive or active) affect their intervention planning and decision making for young children who require augmentative and alternative communication (AAC). A second goal was to determine whether SLPs who work with young children who use AAC target goals in intervention that promote and/or maintain an active communication style. An original survey was designed for the study. The SLP participants were asked to provide information about the design of AAC systems and the communicative opportunities made available to young children with AAC needs. Participants were recruited through email and were asked to respond to a Web-based survey. Eighty-nine preschool SLPs practicing in 20 states across the United States responded to the survey. Results indicated that many of the SLPs classified young children with AAC needs they have worked with as passive communicators. Furthermore, the SLPs reported differences in their intervention practices for children with AAC needs whom they considered active and passive communicators. The return rate for participants was small, and it is difficult to generalize the results. However, it appears that more emphasis needs to be placed on providing interventions that target communication skills that young children who use AAC need in order to be active communicators and to participate fully in their natural contexts. PMID- 22670730 TI - Traditional versus computerized presentation and response methods on a structured AAC assessment tool. AB - This pilot investigation compared participants' performance using traditional versus computerized presentation and response methods on a subtest of the Test of Aided-Symbol PerformanceTM (TASP). Participants were between 6 years and 21 years of age and were using some form of augmentative and alternative communication (AAC). Investigators used a within-subject crossover design, with participants randomly assigned to the administration condition they experienced first. Two months later, participants experienced the second condition. Results showed no significant difference in performance regardless of the administration condition, which supported the investigators' hypothesis. Accepting computerized presentation and response methods for the TASP would allow this measure to be used more broadly and expand the current methods of confidently evaluating options for AAC recommendations. PMID- 22670731 TI - Herb-drug interactions: an overview of systematic reviews. AB - OBJECTIVES: The aim of this overview of systematic reviews (SRs) is to evaluate critically the evidence regarding interactions between herbal medicinal products (HMPs) and synthetic drugs. METHODS: Four electronic databases were searched to identify relevant SRs. RESULTS: Forty-six SRs of 46 different HMPs met our inclusion criteria. The vast majority of SRs were of poor methodological quality. The majority of these HMPs were not associated with severe herb-drug interactions. Serious herb-drug interactions were noted for Hypericum perforatum and Viscum album. The most severe interactions resulted in transplant rejection, delayed emergence from anaesthesia, cardiovascular collapse, renal and liver toxicity, cardiotoxicity, bradycardia, hypovolaemic shock, inflammatory reactions with organ fibrosis and death. Moderately severe interactions were noted for Ginkgo biloba, Panax ginseng, Piper methysticum, Serenoa repens and Camellia sinensis. The most commonly interacting drugs were antiplatelet agents and anticoagulants. CONCLUSION: The majority of the HMPs evaluated in SRs were not associated with drug interactions with serious consequences. However, the poor quality and the scarcity of the primary data prevent firm conclusions. PMID- 22670733 TI - Computer analysis of non-invasive measures of cardiovascular variability for deducing autonomic function and for risk stratification. PMID- 22670734 TI - Time for change: traditional audit or continuous improvement? PMID- 22670735 TI - Medical simulation in 'my world'. PMID- 22670736 TI - Limited pre-operative echocardiography: are the limitations justified? PMID- 22670737 TI - Echocardiographic assessment by anaesthetists. PMID- 22670739 TI - Routine pre-operative echocardiography for detection of aortic stenosis? PMID- 22670740 TI - Awake videolaryngoscopy-assisted tracheal intubation in the morbidly obese. PMID- 22670741 TI - Patient-inserted awake Airtraq((r)) -assisted intubation. PMID- 22670742 TI - Awake tracheal intubation using videolaryngoscopy: importance of blade design. PMID- 22670744 TI - Unexpected behaviour of the bispectral index (BIS) after brain injury. PMID- 22670745 TI - Mortality, BIS and the ketamine conundrum. PMID- 22670746 TI - Postoperative analgesia - still failing to meet the standard. PMID- 22670747 TI - Requirement for critical care in the maternity unit. PMID- 22670748 TI - PCA test protocol delivers potentially fatal morphine overdose. PMID- 22670749 TI - Broken epidural catheter. PMID- 22670750 TI - Throat packs in neuroanaesthesia. PMID- 22670751 TI - Unusual malfunction of a sevoflurane vaporiser. PMID- 22670752 TI - The effect of ionizing radiation on metoprolol. AB - The influence of ionising radiation on physico-chemical properties of metoprolol tartrate (MT) in solid phase was studied. The compound was irradiated by radiation produced by a beam of high-energy electrons in an accelerator, in doses from 25 to 400 kGy, and the possible changes in the samples were detected by organoleptic analysis (colour, forms, clarity), chromatographic and spectrometric methods. Already at the standard sterilisation dose of 25 kGy, the presence of free radicals (0.3764 * 10(16) spin/g) and a decrease in the melting point by 1 degrees C were noted. At higher doses of irradiation products of radiolysis appeared (100 kGy) and the colour was changed from white to pale cream (200 kGy). Our observation was that with increasing mass loss of MT after irradiation with 100, 200 and 400 kGy, the concentration of free radicals increased from 1.0330 to 1.6869 * 10(16) spin/g. The radiolytic yield of total radiolysis was 4.54 * 10(7) mol/J for 100 kGy, 7.42 * 10(7) mol/J for 200 kGy and 4.74 * 10(7) mol/J for 400 kGy. No significant changes were observed in the character of FT-IR spectra, but in UV an increase in intensity of the band at the analytical wavelength was noted. As follows from the results MT shows high radiochemical stability for the typical sterilisation doses 25-50 kGy, and will probably be able to be sterilised by radiation in the dose of 25 kGy. PMID- 22670753 TI - Host specificity of Sporisorium reilianum is tightly linked to generation of the phytoalexin luteolinidin by Sorghum bicolor. AB - The smut fungus Sporisorium reilianum occurs in two varieties (S. reilianum f. sp. reilianum and S. reilianum f. sp. zeae) that cause head smut disease on sorghum and maize, respectively. Prior to plant infection, compatible haploid sporidia of S. reilianum fuse to form infectious dikaryotic hyphae that penetrate the leaf surface, spread throughout the plant, and reach the inflorescences, in which spore formation occurs. To elucidate the basis of host specificity of the two S. reilianum varieties, we compared disease etiology of S. reilianum f. sp. reilianum and S. reilianum f. sp. zeae on sorghum and maize. Both varieties could penetrate and multiply in both hosts. However, red spots appeared on inoculated leaves after sorghum infection with S. reilianum f. sp. zeae. Using matrix assisted laser desorption-ionization time of flight analysis of leaf extracts, we show that sorghum reacts with the production of the red and orange phytoalexins luteolinidin and apigeninidin upon colonization by S. reilianum f. sp. zeae but not by S. reilianum f. sp. reilianum. Using in vitro growth assays, we demonstrate that luteolinidin but not apigeninidin slows vegetative growth of both S. reilianum f. sp. zeae and S. reilianum f. sp. reilianum. However, the phytoalexin biosynthesis gene SbDFR3 is only induced in sorghum after infection with S. reilianum f. sp. zeae, as shown by quantitative real-time polymerase chain reaction. This suggests that regulation of luteolinidin biosynthesis determines infection success of S. reilianum on sorghum. PMID- 22670754 TI - Arabinogalactan proteins occur in the free-living cyanobacterium genus Nostoc and in plant-Nostoc symbioses. AB - Arabinogalactan proteins (AGP) are a diverse family of proteoglycans associated with the cell surfaces of plants. AGP have been implicated in a wide variety of plant cell processes, including signaling in symbioses. This study investigates the existence of putative AGP in free-living cyanobacterial cultures of the nitrogen-fixing, filamentous cyanobacteria Nostoc punctiforme and Nostoc sp. strain LBG1 and at the symbiotic interface in the symbioses between Nostoc spp. and two host plants, the angiosperm Gunnera manicata (in which the cyanobacterium is intracellular) and the liverwort Blasia pusilla (in which the cyanobacterium is extracellular). Enzyme-linked immunosorbent assay, immunoblotting, and immunofluorescence analyses demonstrated that three AGP glycan epitopes (recognized by monoclonal antibodies LM14, MAC207, and LM2) are present in free living Nostoc cyanobacterial species. The same three AGP glycan epitopes are present at the Gunnera-Nostoc symbiotic interface and the LM2 epitope is detected during the establishment of the Blasia-Nostoc symbiosis. Bioinformatic analysis of the N. punctiforme genome identified five putative AGP core proteins that are representative of AGP classes found in plants. These results suggest a possible involvement of AGP in cyanobacterial-plant symbioses and are also suggestive of a cyanobacterial origin of AGP. PMID- 22670755 TI - Development of viral vectors based on Citrus leaf blotch virus to express foreign proteins or analyze gene function in citrus plants. AB - Viral vectors have been used to express foreign proteins in plants or to silence endogenous genes. This methodology could be appropriate for citrus plants that have long juvenile periods and adult plants that are difficult to transform. We developed viral vectors based on Citrus leaf blotch virus (CLBV) by duplicating a minimum promoter (92 bp) either at the 3' untranslated region (clbv3'pr vector) or at the intergenic region between the movement and coat protein (CP) genes (clbvINpr vector). The duplicated fragment (-42/+50) around the transcription start site of the CP subgenomic RNA (sgRNA) had the full promoter activity and induced synthesis of a new sgRNA in infected plants. Agroinoculation with these vectors resulted in systemic infection of Nicotiana benthamiana and the resulting virions systemically infected citrus plants. A clbvINpr vector carrying the green fluorescent protein (GFP) gene expressed GFP in citrus plants and triggered gfp silencing in gfp-transgenic citrus plants, and vectors carrying fragments of the phytoene desaturase or the magnesium chelatase genes incited a silencing phenotype in citrus plants. These silenced phenotypes persisted in successive flushes. Because CLBV infections are symptomless in most citrus species, the effective silencing induced by CLBV-derived vectors will be helpful to analyze citrus gene function. PMID- 22670756 TI - Expression of the human NAD(P)-metabolizing ectoenzyme CD38 compromises systemic acquired resistance in Arabidopsis. AB - Plant systemic acquired resistance (SAR) is a long-lasting, broad-spectrum immune response that is mounted after primary pathogen infection. Although SAR has been extensively researched, the molecular mechanisms underlying its activation have not been completely understood. We have previously shown that the electron carrier NAD(P) leaks into the plant extracellular compartment upon pathogen attack and that exogenous NAD(P) activates defense gene expression and disease resistance in local treated leaves, suggesting that extracellular NAD(P) [eNAD(P)] might function as a signal molecule activating plant immune responses. To further establish the function of eNAD(P) in plant immunity, we tested the effect of exogenous NAD(P) on resistance gene-mediated hypersensitive response (HR) and SAR. We found that exogenous NAD(P) completely suppresses HR-mediated cell death but does not affect HR-mediated disease resistance. Local application of exogenous NAD(P) is unable to induce SAR in distal tissues, indicating that eNAD(P) is not a sufficient signal for SAR activation. Using transgenic Arabidopsis plants expressing the human NAD(P)-metabolizing ectoenzyme CD38, we demonstrated that altering eNAD(P) concentration or signaling compromises biological induction of SAR. This result suggests that eNAD(P) may play a critical signaling role in activation of SAR. PMID- 22670757 TI - RNA silencing and plant viral diseases. AB - RNA silencing plays a critical role in plant resistance against viruses, with multiple silencing factors participating in antiviral defense. Both RNA and DNA viruses are targeted by the small RNA-directed RNA degradation pathway, with DNA viruses being also targeted by RNA-directed DNA methylation. To evade RNA silencing, plant viruses have evolved a variety of counter-defense mechanisms such as expressing RNA-silencing suppressors or adopting silencing-resistant RNA structures. This constant defense-counter defense arms race is likely to have played a major role in defining viral host specificity and in shaping viral and possibly host genomes. Recent studies have provided evidence that RNA silencing also plays a direct role in viral disease induction in plants, with viral RNA silencing suppressors and viral siRNAs as potentially the dominant players in viral pathogenicity. However, questions remain as to whether RNA silencing is the principal mediator of viral pathogenicity or if other RNA-silencing-independent mechanisms also account for viral disease induction. RNA silencing has been exploited as a powerful tool for engineering virus resistance in plants as well as in animals. Further understanding of the role of RNA silencing in plant-virus interactions and viral symptom induction is likely to result in novel anti-viral strategies in both plants and animals. PMID- 22670758 TI - Assessing the association between self-report items for HIV pill adherence and biological measures. AB - Sub-optimal pill adherence to antiretroviral treatment among HIV-infected persons may have serious consequences, including a decline in health status, eventually leading to death. We developed an instrument to assess self-reported pill adherence to antiretroviral therapy (ART) among patients attending a public health clinic in South Africa. The instrument, based on previously published guidelines, consisted of five questions and a visual analogue scale assessing pill adherence behaviour and was administered to 101 patients living with HIV who commenced ART at least six months prior to data collection. The scale showed fair but not excellent internal consistency (alpha reliability=0.63). Participants reported generally high levels of pill adherence. One question on the scale was able to distinguish between a detectable and a lower than detectable viral load (p<0.01). Yet, the combined items did not predict biologically measured adherence. Despite good comprehensibility of items, the study may have been vulnerable to recall and social desirability bias and was conducted only among clinic attenders rather than those with varied levels of clinic attendance, which is potentially a matter for further study. PMID- 22670759 TI - Imaging and 3D morphological analysis of collagen fibrils. AB - The recent booming of multiphoton imaging of collagen fibrils by means of second harmonic generation microscopy generates the need for the development and automation of quantitative methods for image analysis. Standard approaches sequentially analyse two-dimensional (2D) slices to gain knowledge on the spatial arrangement and dimension of the fibrils, whereas the reconstructed three dimensional (3D) image yields better information about these characteristics. In this work, a 3D analysis method is proposed for second harmonic generation images of collagen fibrils, based on a recently developed 3D fibre quantification method. This analysis uses operators from mathematical morphology. The fibril structure is scanned with a directional distance transform. Inertia moments of the directional distances yield the main fibre orientation, corresponding to the main inertia axis. The collaboration of directional distances and fibre orientation delivers a geometrical estimate of the fibre radius. The results include local maps as well as global distribution of orientation and radius of the fibrils over the 3D image. They also bring a segmentation of the image into foreground and background, as well as a classification of the foreground pixels into the preferred orientations. This accurate determination of the spatial arrangement of the fibrils within a 3D data set will be most relevant in biomedical applications. It brings the possibility to monitor remodelling of collagen tissues upon a variety of injuries and to guide tissues engineering because biomimetic 3D organizations and density are requested for better integration of implants. PMID- 22670760 TI - A new binding site involving the C-terminal domain to design specific inhibitors of PepX. AB - PepX is a X-prolyl dipeptidyl aminopeptidase of S15 family that cleaves dipeptides from the N-terminus of polypeptides having a proline or alanine residue at the second position. Involved in bacterial nutrition and in peptide maturation, this serine exopeptidase, counterpart of the mammalian DDP-4, has been proposed to play a role in pathogenicity for Streptococci and to be a promising target against trypanosomes. Searching for specific inhibitors, we undertook docking simulations on the whole surface of PepX from Lactococcus lactis, type example of the S15 family, which revealed a new putative binding site in connection with the active site and involving the C-terminal domain. Accordingly to the results of the computations, we synthesized two peptidomimetics of low molecular weight: the valinephenylpiperazine and the valine-isopropylpiperazine that can accommodate to this putative binding site. Experiments revealed that the valine-phenylpiperazine was an uncompetitive inhibitor whereas the valine-isopropylpiperazine showed to be an activator of the enzyme activity. The valine-phenylpiperazine is interacting with ASN 379, GLU 383, GLU 474, residues in connection with the specificity and active sites, and with the residues from the C-terminal domain LEU 693, GLU 710 and GLN 712. These results point out a role of the C-terminal domain in controlling access to the active site of enzymes of the S15 family, like PepX, the cocaine esterase or the alpha-amino acid ester hydrolase, and could have applications in human health giving new perspectives to struggle against streptococci or trypanosomes by designing inhibitors specific to the S15 family of enzymes. PMID- 22670761 TI - Effect of cadmium sulfide quantum dots on physical properties of R-phycoerythrin as a protein matrix. AB - The synthesis and analysis of nanostructures in the cavities of protein molecules is a promising research field in the industry of nanosystems. In this study, atomic force microscopy (AFM) has been used to evaluate the properties of CdS quantum dots synthesized in the tunnel cavities of R-phycoerythrin, a 290 kDa water-soluble pigment protein responsible for light harvesting in red algae. It has been shown that R-phycoerythrin dissolved in deionized water to a concentration of 50 MUg/ml is prone to self-organization into regular spatial structures upon adsorption on the surface of mica, but no such structuring takes place in films prepared from R-phycoerythrin solutions diluted tenfold. In the latter case, protein molecules are deformed, as judged from the analysis of the surface profile. R-phycoerythrin with CdS quantum dots in protein cavities (the concentration of the preparation was (48 MUg/ml) loses the self-organization ability and is not deformed upon adsorption on the mica surface. Analysis of AFM images by flicker-noise spectroscopy has shown that incorporation of CdS quantum dots into R-phycoerythrin molecules provides for "smoothing" of the protein surface, with various irregularities being leveled off. Conversely, the irregularity of the protein surface increases when R-phycoerythrin molecules are arranged into three-dimensional branching structures. It is concluded that CdS quantum dots interfere with protein-protein interactions and restrain the conformational mobility of the protein. The anomalously rigid structure of R phycoerythrin in the presence of CdS is due to its conformational rearrangements during the synthesis of quantum dot. PMID- 22670762 TI - Effects of thioredoxin: SUMO and intein on soluble fusion expression of an antimicrobial peptide OG2 in Escherichia coli. AB - OG2 is a modified antimicrobial peptide of Palustrin-OG1 (OG1), which is derived from Odorrana grahami frog. OG2 has shown much higher selective antimicrobial activity and lower hemolytic activity than OG1, indicating OG2 may be a promising antimicrobial agent. In this study, we investigated three fusion partners, including thioredoxin, Mxe GyrA intein, and small ubiquitin-like modifier (SUMO), each fused with OG2, and examined their effects on the expression level and solubility of OG2 in Escherichia coli. The codon-optimized OG2 gene was cloned into pET32a (+) and pTWIN1 for fusion with thioredoxin and Mxe GyrA intein, respectively. In addition, the SUMO-OG2 gene was amplified by splice overlap extension PCR method and was cloned into pET30a (+). All recombinant plasmids were then transformed into E. coli BL21(DE3)pLysS, and the expressed fusion proteins were verified. Upon isopropyl beta-D-1-thiogalactopyranoside (IPTG) induction, OG2 fused with thioredoxin (Trx-OG2) showed the highest yield as a soluble fusion protein (50 mg/L), followed by Mxe GyrA intein (44 mg/L) and SUMO (11 mg/L). The thioredoxin-fused protein (Trx-OG2) was then purified by nickel nitrilotriacetic acid chromatography and desalted by Sephadex G25. The OG2 released by both tobacco etch virus protease and enterokinase from Trx-OG2 showed strong antimicrobial activity against Staphylococcus aureus ATCC25923. PMID- 22670763 TI - A single amino acid residue determines the ratio of hydrolysis to transglycosylation catalyzed by beta-glucosidases. AB - The propensity to catalysis of transglycosylation of the beta-glucosidase Tmbetagly is higher than for Sfbetagly. Moreover the propensity to catalysis of transglycosylation is directly proportional to the substrate concentration for Tmbetagly, whereas for Sfbetagly it is constant. For instance, 60% of a Tmbetagly sample catalyzes transglycosylation reactions at 40 mM p-nitrophenyl beta glucoside, whereas only 40% is engaged in hydrolysis of this substrate. For Sfbetagly the fraction involved in transglycosylation is only 30 %. In addition, 48 % of a Tmbetagly sample catalyzes transglycosylation reactions at 8 mM methylumbelliferyl beta-glucoside, whereas Sfbetagly does not catalyze transglycosylation using this substrate. Interestingly, these Tmbetagly properties were grafted into Sfbetagly by a single replacement of a residue forming a channel involved in supplying the catalytic water molecules for attack on the covalent intermediate present in the reaction catalyzed by beta glucosidases. Hence a single residue determines the ratio of hydrolysis to transglycosylation reactions catalyzed by these beta-glucosidases. PMID- 22670764 TI - Why is glycine not a part of the osmoticum in the urea-rich cells? AB - Kidney cells of animals including human and marine invertebrates contain high amount of the protein denaturant, urea. Methylamine osmolytes are generally believed to offset the harmful effects of urea on proteins in vitro and in vivo. In this study we have investigated the possibility of glycine to counteract the effects of urea on three proteins by measuring thermodynamic stability, DeltaGD degrees and functional activity parameters (K(m) and k(cat)). We discovered that glycine does not counteract the effects of urea in terms of both protein stability and functional activity. We also observed that the glycine alone is compatible with enzymes function and increases protein stability in terms of T(m) (midpoint of thermal denaturation) to a great extent. Our study indicates that a most probable reason for the absence of a stabilizing osmolyte, glycine in the urea-rich cells is due to the fact that this osmolyte is non-protective to macromolecules against the hostile effects of urea, and hence is not chosen by evolutionary selection pressure. PMID- 22670765 TI - Identification of a novel peptide ligand of human transfrrin receptor 1 for targeted tumor delivery drug. AB - Human transferrin receptor 1 (TfR1) is expressed on malignant cells at levels several fold higher than those on normal cells and its expression can be correlated with tumor stage or cancer progression. It is a potentially rational target for drug delivery. To identify novel ligands which can recognize the TfR1 specifically, a random phage displayed 12-mer peptide library was screened and two consensus motifs of the peptides which are displayed by the positive phages RXR and RXXXR (x is any amino acid) were yield. The phage displaying peptide SPRPRHTLRLSL (designated as B18) exhibited the highest affinity to TfR1 in phage ELISA and B18 could bind to TfR1 specifically in a dose dependent manner. The flow cytometry assay and immunocellularchemistry assay showed that the B18 could bind to TfR1 positive carcinoma cells with specificity. In addition, the biodistribution assay indicated that B18 could home to TfR1 positive tumor tissue specifically. Our study suggests that the peptide exhibited by B18 is a potentially promising targeting peptide for tumor diagnosis and treatment. PMID- 22670766 TI - Inkjet printed fractal-connected electrodes with silver nanoparticle ink. AB - The development of a simple and reliable method for nanoparticles-based ink in an aqueous solution is still a challenge for its inkjet printing application. Herein, we demonstrate the inkjet printing of fractal-aggregated silver (Ag) electrode lines on substrates. Spherical, monodisperse Ag nanoparticles have been synthesized using silver nitrate as a precursor, ethylene glycol as a reducing agent, and polyvinyl pyrrollidone as a capping agent. As-synthesized pure Ag nanoparticles were well dispersed in water-ethylene glycol mixture, which was directly used as an ink for inkjet printing. Using this ink, the Ag electrodes of fractal-connected lines were printed on Si/SiO2, glass, and polymer substrates. The fractal-connected Ag lines were attributed to the diffusion-limited aggregation of Ag nanoparticles and the effect of annealing on conductivity was also examined. PMID- 22670767 TI - Wide-open flaps are key to urease activity. AB - Substrate ingress and product egress from the active site of urease is tightly controlled by an active-site flap. Molecular dynamics simulations of urease have revealed a previously unobserved wide-open flap state that, unlike the well characterized closed and open states, allows ready access to the metal cluster in the active site. This state is easily reached from the open state via low free energy barriers. Additionally, we have found that even when the flap is closed, a region of the binding pocket is solvent-exposed, leading to the hypothesis that it may act as a substrate/product reservoir. The newly identified wide-open state offers further opportunities for small-molecule drug discovery by defining a more extensive active-site pocket than has been previously described. PMID- 22670768 TI - RuH2(CO)(PPh3)3 catalyzed selective formation of 1,4-disubstituted triazoles from cycloaddition of alkynes and organic azides. AB - The ruthenium hydride complex RuH(2)(CO)(PPh(3))(3) was found to be an effective catalyst for the cycloaddition reactions of terminal alkynes and azides. In the presence of RuH(2)(CO)(PPh(3))(3), various azides reacted with a range of terminal alkynes to produce 1,4-disubstituted 1,2,3-triazoles with 100% selectivity and moderate to excellent yields. PMID- 22670769 TI - Crystal structure of an activated variant of small heat shock protein Hsp16.5. AB - How does the sequence of a single small heat shock protein (sHSP) assemble into oligomers of different sizes? To gain insight into the underlying structural mechanism, we determined the crystal structure of an engineered variant of Methanocaldococcus jannaschii Hsp16.5 wherein a 14 amino acid peptide from human heat shock protein 27 (Hsp27) was inserted at the junction of the N-terminal region and the alpha-crystallin domain. In response to this insertion, the oligomer shell expands from 24 to 48 subunits while maintaining octahedral symmetry. Oligomer rearrangement does not alter the fold of the conserved alpha crystallin domain nor does it disturb the interface holding the dimeric building block together. Rather, the flexible C-terminal tail of Hsp16.5 changes its orientation relative to the alpha-crystallin domain which enables alternative packing of dimers. This change in orientation preserves a peptide-in-groove interaction of the C-terminal tail with an adjacent beta-sandwich, thereby holding the assembly together. The interior of the expanded oligomer, where substrates presumably bind, retains its predominantly nonpolar character relative to the outside surface. New large windows in the outer shell provide increased access to these substrate-binding regions, thus accounting for the higher affinity of this variant to substrates. Oligomer polydispersity regulates sHSPs chaperone activity in vitro and has been implicated in their physiological roles. The structural mechanism of Hsp16.5 oligomer flexibility revealed here, which is likely to be highly conserved across the sHSP superfamily, explains the relationship between oligomer expansion observed in disease-linked mutants and changes in chaperone activity. PMID- 22670770 TI - Identification of enterodiol as a masker for caffeine bitterness by using a pharmacophore model based on structural analogues of homoeriodictyol. AB - Starting from previous structure-activity relationship studies of taste modifiers based on homoeriodictyol, dihydrochalcones, deoxybenzoins, and trans-3 hydroxyflavones as obvious analogues were investigated for their masking effect against caffeine. The most active compounds of the newly investigated taste modifiers were phloretin, the related dihydrochalcones 3-methoxy-2',4,4' trihydroxydihydrochalcone and 2',4-dihydroxy-3-methoxydihydrochalcone, and the deoxybenzoin 2-(4-hydroxy-3-methoxyphenyl)-1-(4-hydroxyphenyl)ethanone. Starting with the whole set of compounds showing activity >22%, a (Q)SAR pharmacophore model for maskers of caffeine bitterness was calculated to explain the structural requirements. After docking of the pharmacophore into a structural model of the broadly tuned bitter receptor hTAS2R10 and docking of enterolactone and enterodiol as only very weakly related structures, it was possible to predict qualitatively their modulating activity. Enterodiol (25 mg L(-1)) reduced the bitterness of the 500 mg L(-1) caffeine solution by about 30%, whereas enterolactone showed no masking but a slight bitter-enhancing effect. PMID- 22670771 TI - Is there a statistical relationship between economic crises and changes in government health expenditure growth? an analysis of twenty-four European countries. AB - OBJECTIVE: To identify whether, by what means, and the extent to which historically, government health care expenditure growth in Europe has changed following economic crises. DATA SOURCES: Organization for Economic Cooperation and Development Health Data 2011. STUDY DESIGN: Cross-country fixed effects multiple regression analysis is used to determine whether statutory health care expenditure growth in the year after economic crises differs from that which would otherwise be predicted by general economic trends. Better understanding of the mechanisms involved is achieved by distinguishing between policy responses which lead to cost-shifting and all others. FINDINGS: In the year after an economic downturn, public health care expenditure grows more slowly than would have been expected given the longer term economic climate. Cost-shifting and other policy responses are both associated with these slowdowns. However, while changes in tax-derived expenditure are associated with both cost-shifting and other policy responses following a crisis, changes in expenditure derived from social insurance have been associated only with changes in cost-shifting. CONCLUSIONS: Disproportionate cuts to the health sector, as well as reliance on cost-shifting to slow growth in health care expenditure, serve as a warning in terms of potentially negative effects on equity, efficiency, and quality of health services and, potentially, health outcomes following economic crises. PMID- 22670772 TI - Cytosine-phosphate-guanosine-DNA induces CD274 expression in human B cells and suppresses T helper type 2 cytokine production in pollen antigen-stimulated CD4 positive cells. AB - Co-stimulatory molecules are important for regulating T cell activation and immune response. CD274 [programmed death ligand 1 (PD-L1), B7-H1] has emerged as an important immune modulator that can block T cell receptor signalling. We have investigated whether PD-L1 and other co-stimulatory ligands could be expressed in human B cells stimulated by cytosine-phosphate-guanosine (CpG)-DNA. CpG-DNA strongly induced the co-inhibitory molecule ligand, PD-L1, of human B cells. Results show that nuclear factor-kappa B (NF-kappaB) signalling is involved directly in CpG-DNA-induced PD-L1 expression in human B cells. We sought to determine the effect of CpG-DNA-treated B cells on T helper type 2 (Th2) cytokine production in Cry j 1 (Japanese pollen antigen)-stimulated human CD4-positive cells from patients with seasonal allergic rhinitis caused by Japanese cedar pollen. CpG-DNA-treated B cells reduced Cry j 1-induced interleukin (IL)-5 and IL 13 production in CD4-positive cells. When the binding of PD-1 to PD-L1 was inhibited by PD-1-immunoglobulin (Ig), this chimera molecule reversed the previously described reductions in IL-5 and IL-13 production. In contrast, the CpG B-treated B cells increased both interferon (IFN)-gamma and IL-12 production in the presence of Cry j 1-stimulated CD4-positive cells. CpG-DNA simultaneously reduced the expression of B7RP-1 [also known as inducible co-stimulator ligand (ICOSL), B7-H2] and the ligand of CD30 (CD30L). These results indicate that CpG DNA induces co-inhibitory molecule ligand PD-L1 expression in human B cells and PD-L1 can suppress Th2 cytokine production in Cry j 1-stimulated CD4-positive cells, while CpG-DNA increased Th1 cytokine production and reduced the expression of co-stimulatory molecule ligands that can promote Th2 inflammatory responses. PMID- 22670773 TI - Alteration of CD1 expression in multiple sclerosis. AB - Studies of multiple sclerosis (MS) have concentrated mainly on antigen presentation of peptides derived from the myelin sheath, while the implication of lipid antigen has been less explored in this pathology. As the extracellular environment regulates expression of the lipid antigen-presenting molecule CD1, we have examined whether sera from patients alters CD1 surface expression in monocyte-derived dendritic cells. We have shown that: (i) CD1 group 1 proteins were highly expressed in the presence of MS sera; (ii) sera from MS patients differentially regulated CD1 group 1 versus CD1 group 2 molecular expression; and (iii) CD1 was expressed strongly in monocytes from MS patients under immunosuppressive treatment. Overall, these results reveal that CD1 expression is modified in MS and provide novel information on the regulation of lipid antigen presentation in myeloid cells. PMID- 22670775 TI - Oral treatment with Hev b 13 ameliorates experimental colitis in mice. AB - Hev b 13 is an allergenic esterase obtained from the rubber tree Hevea brasiliensis, which has been shown recently to induce human mononuclear cells to release interleukin (IL)-10 in vitro. This immunoregulatory cytokine appears to play an important role in preventing inflammation and mucosal damage in animal models of colitis and in Crohn's disease patients. The aim of this study was to evaluate the therapeutic effect of Hev b 13 in mice with 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis. Two hours following colonic instillation of the haptenizing agent, and daily thereafter for 5 days, Hev b 13 was administered by oral gavage. In mice treated with daily doses of either 0.5 mg/kg or 5.0 mg/kg of Hev b 13, the clinical signs of diarrhoea, rectal prolapse and body weight loss and also histological damage of the distal colon, were reduced significantly, in comparison with water-treated diseased mice. These findings suggest a potent anti-inflammatory activity of Hev b 13; this activity is speculated to be related to its interaction with cells from the immune system. PMID- 22670774 TI - Cytokine/chemokine profiles contribute to understanding the pathogenesis and diagnosis of primary Sjogren's syndrome. AB - To investigate the pathogenesis of localized autoimmune damage in Sjogren's syndrome (SS) by examining the expression patterns of cytokines, chemokines and chemokine receptors at sites of autoimmune damage. mRNA expression of these molecules in the labial salivary glands (LSGs) and peripheral blood mononuclear cells (PBMCs) from 36 SS patients was examined using a real-time polymerase chain reaction-based method. Subsets of the infiltrating lymphocytes and chemokines/chemokine receptors expression in the LSG specimens were examined by immunohistochemistry. Cytokines/chemokine concentrations in the saliva were analysed using flow cytometry or enzyme-linked immunosorbent assay. mRNA expression of T helper type 1 (Th1) cytokines, chemokines and chemokine receptors was higher in LSGs than in PBMCs. In contrast, mRNA expression of Th2 cytokines, chemokines [thymus and activation-regulated chemokine (TARC/CCL17), macrophage derived chemokine (MDC/CCL22)] and chemokine receptor (CCR4) was associated closely with strong lymphocytic accumulation in LSGs. Furthermore, TARC and MDC were detected immunohistochemically in/around the ductal epithelial cells in LSGs, whereas CCR4 was detected on infiltrating lymphocytes. The concentrations of these cytokines/chemokines were significantly higher in the saliva from SS patients than those from controls, and the concentrations of Th2 cytokines/chemokines were associated closely with strong lymphocytic accumulation in LSGs. These results suggest that SS might be initiated and/or maintained by Th1 and Th17 cells and progress in association with Th2 cells via the interaction between particular chemokines/chemokine receptors. Furthermore, the measurement of cytokines/chemokines in saliva is suggested to be useful for diagnosis and also to reveal disease status. PMID- 22670776 TI - Intravenous immunoglobulin does not increase FcgammaRIIB expression levels on monocytes in children with immune thrombocytopenia. AB - Intravenous immunoglobulin (IVIG) produces a rapid and prolonged increase in the platelet counts of children with immune thrombocytopenia (ITP). The mechanism of IVIG efficacy in a murine model of ITP has been reported to operate through an IVIG-mediated increase in the expression of the inhibitory Fc receptor FcgammaRIIB(CD32B) on splenic macrophages. This investigation examined whether IVIG administration results in a similar increase in FcgammaRIIB expression on peripheral blood CD14(+) monocytes in 20 children with ITP. FcgammaRIIB expression on peripheral blood monocytes was measured by flow cytometry in ITP patients, before and after IVIG therapy, as well as in control subjects. Peripheral blood monocytes were labelled with fluorescent-specific antibodies. There were no significant differences in the absolute number of [corrected] CD14(+) CD32B(+) monocytes, and [corrected] the percentages of CD14(+) CD32B(+) cells in mononuclear cells or monocytes. [corrected]. We suggest that IVIG does not increase FcgammaRIIB expression in peripheral blood monocytes in children with ITP. PMID- 22670777 TI - Mannan-binding lectin (MBL)-associated serine protease-1 (MASP-1), a serine protease associated with humoral pattern-recognition molecules: normal and acute phase levels in serum and stoichiometry of lectin pathway components. AB - The pattern-recognition molecules mannan-binding lectin (MBL) and the three ficolins circulate in blood in complexes with MBL-associated serine proteases (MASPs). When MBL or ficolin recognizes a microorganism, activation of the MASPs occurs leading to activation of the complement system, an important component of the innate immune system. Three proteins are produced from the MASP1 gene: MASP-1 and MASP-3 and MAp44. We present an assay specific for MASP-1, which is based on inhibition of the binding of anti-MASP-1-specific antibody to MASP-1 domains coated onto microtitre wells. MASP-1 was found in serum in large complexes eluting in a position corresponding to ~600 kDa after gel permeation chromatography in calcium-containing buffer and as monomers of ~75 kDa in dissociating buffer. The concentration of MASP-1 in donor sera (n = 105) was distributed log-normally with a median value of 11 ug/ml (range 4-30 ug/ml). Serum and citrate plasma levels were similar, while the values in ethylenediamine tetraacetic acid plasma were slightly lower and in heparin plasma were 1.5 times higher than in serum. MASP-1 was present at adult level at 1 year of age, while it was 60% at birth. In normal healthy individuals the level of MASP-1 was stable throughout a 2-month period. After induction of an acute-phase reaction by operation we found an initial short decrease, concomitant with an increase in C reactive protein levels, followed by an increase, doubling the MASP-1 concentration after 2 days. The present data prepare the ground for studies on the associations of MASP-1 levels with disease. PMID- 22670778 TI - Circulating ficolin-2 and ficolin-3 in normal pregnancy and pre-eclampsia. AB - Ficolins are soluble molecules of the innate immune system that recognize carbohydrate molecules on microbial pathogens, apoptotic and necrotic cells. They act through two distinct routes: initiating the lectin pathway of complement activation and mediating a primitive opsonophagocytosis. In this study, we measured plasma levels of ficolin-2 and ficolin-3 in 60 pre-eclamptic patients, 60 healthy pregnant women and 59 healthy non-pregnant women by enzyme-linked immunosorbent assay (ELISA). Circulating levels of complement activation products (C4d, C3a, SC5b9), angiogenic factors (soluble fms-like tyrosine kinase-1, placental growth factor) and markers of endothelial activation (von Willebrand factor antigen), endothelial injury (fibronectin) and trophoblast debris (cell free fetal DNA) were also determined. Plasma levels of ficolin-2 were significantly lower in healthy pregnant than in healthy non-pregnant women, while ficolin-3 levels did not differ significantly between the two groups. Furthermore, pre-eclamptic patients had significantly lower ficolin-2 and ficolin 3 concentrations than healthy non-pregnant and pregnant women. In the pre eclamptic group, plasma ficolin-2 levels showed a significant positive correlation with serum placental growth factor (PlGF) concentrations and significant inverse correlations with serum levels of soluble fms-like tyrosine kinase-1 (sFlt-1), blood urea nitrogen and creatinine, serum lactate dehydrogenase activities, as well as with plasma VWF:antigen, fibronectin and cell-free fetal DNA concentrations. In conclusion, circulating levels of ficolin 2 are decreased in the third trimester of normal pregnancy. There is a further decrease in plasma ficolin-2 concentrations in pre-eclampsia, which might contribute to the development of the maternal syndrome of the disease through impaired removal of the trophoblast-derived material released into the maternal circulation by the hypoxic and oxidatively stressed pre-eclamptic placenta. PMID- 22670779 TI - Comparison of American and European practices in the management of patients with primary immunodeficiencies. AB - Primary immunodeficiency diseases (PIDs) comprise a heterogeneous group of rare disorders. This study was devised in order to compare management of these diseases in the northern hemisphere, given the variability of practice among clinicians in North America. The members of two international societies for clinical immunologists were asked about their management protocols in relation to their PID practice. An anonymous internet questionnaire, used previously for a survey of the American Academy of Allergy, Asthma and Immunology (AAAAI), was offered to all full members of the European Society for Immunodeficiency (ESID). The replies were analysed in three groups, according to the proportion of PID patients in the practice of each respondent; this resulted in two groups from North America and one from Europe. The 123 responses from ESID members (23.7%) were, in the majority, very similar to those of AAAAI respondents, with > 10% of their practice devoted to primary immunodeficiency. There were major differences between the responses of these two groups and those of the general AAAAI respondents whose clinical practice was composed of < 10% of PID patients. These differences included the routine use of intravenous immunoglobulin therapy (IVIg) for particular types of PIDs, initial levels of IVIg doses, dosing intervals, routine use of prophylactic antibiotics, perceptions of the usefulness of subcutaneous immunoglobulin therapy (SCIg) and of the risk to patients' health of policies adopted by health-care funders. Differences in practice were identified and are discussed in terms of methods of health-care provision, which suggest future studies for ensuring continuation of appropriate levels of immunoglobulin replacement therapies. PMID- 22670780 TI - Retraction. The European internet-based patient and research database for primary immunodeficiencies. PMID- 22670781 TI - How afraid are you of having blood drawn from your arm? A simple fear question predicts vasovagal reactions without causing them among high school donors. AB - BACKGROUND: We previously demonstrated in a group of mostly experienced blood donors that fear of blood draws was a significant predictor of vasovagal reactions. Importantly, being asked about one's fear immediately before donation did not increase reaction rates. This study further evaluates the relationship between fear and reactions among high school blood donors, who are known to be at a relatively greater risk for vasovagal reactions. STUDY DESIGN AND METHODS: Immediately after completing the blood donor health screening, 17- and 18-year old high school students were asked about their fear of having blood drawn. Based on a random selection, the fear question was administered in approximately half of the schools, resulting in a final sample of 1715 donors who did and 1692 donors who did not answer the fear question. RESULTS: Fear was a significant predictor of donor reactions and remained a significant independent predictor (along with estimated blood volume and donor sex) in a logistic regression analysis. There was no difference in the proportion of reactions observed between those who did and did not answer the predonation fear question. CONCLUSION: Consistent with previous evidence in older and more experienced blood donors, these findings indicate that assessing fear of blood draws may help to identify those who are most likely to experience vasovagal reactions among young donors without increasing the frequency of such reactions. PMID- 22670782 TI - Enhanced dissolution and systemic availability of albendazole formulated as solid dispersions. AB - Solid dispersions (SDs) containing the anthelmintic compound albendazole (ABZ) and either Pluronic 188 (P 188) or polyethylene glycol 6000 (PEG 6000) as hydrophilic carriers were formulated. Drug-polymers interactions in solid state were investigated using different techniques. Only a 4% of total ABZ was dissolved at 5 min post-incubation, reaching dissolution rates of 32.8% (PEG 6000) and 69.4% (P 188) in SDs. In this way, P 188 was substantially more efficient as ABZ dissolution promoter in comparison to PEG 6000, especially at the initial stages of the dissolution processes (<30 min). An increased systemic availability (p < 0.001) was obtained when ABZ was administered as ABZ-P 188 SDs, with a 50% enhancement in systemic exposure (AUC values) compared to treatment with an ABZ suspension. Consistently, the Cmax increased 130% (p < 0.001) following treatment with P 188 based SD ABZ formulation. For the ABZ-PEG 6000 SD formulation, the favorable effect on ABZ systemic availability did not reached statistical significance compared to the control group. The study reported here showed the utility of pharmacokinetic assays performed on mice as a model for preliminary drug formulation screening studies. PMID- 22670783 TI - Tachycardia associated with twin atrioventricular nodes in an infant with heterotaxy and interruption of inferior vena cava. AB - We report a 12-month-old boy with heterotaxy and interruption of inferior vena cava who showed sustained tachycardia associated with twin atrioventricular nodes (AVNs). Atrioventricular reciprocating tachycardia with antegrade conduction through the posterior AVN and retrograde conduction through the anterior AVN were successfully ablated using an upper approach from the left internal jugular vein. PMID- 22670784 TI - High-pressure gas phase femtosecond laser ionization mass spectrometry. AB - We describe a novel ion source for analytical mass spectrometry based on femtosecond laser ionization at pressures at and above atmospheric and characterize its performance when coupled to a tandem quadrupole/time-of-flight mass spectrometer. We assess source saturation limits, ionization and sampling efficiencies, the effective ionization volume, and limits of detection. We demonstrate 100% efficient ionization for a set of organic compounds and show that the degree of ion fragmentation over a range of laser powers is favorable compared to electron impact ionization, especially in that a substantial parent ion signal is always observed. We show how collisional cooling plays a role in controlling fragmentation at high pressures and address how ion-molecule chemistry can be controlled or exploited. High-pressure femtosecond laser ionization will allow "universal" and efficient ionization, presenting a research direction that will broaden the options for gas phase analysis beyond the capabilities of electron impact ionization. PMID- 22670789 TI - Fifth Conversation in the Discipline Biomolecular Stereodynamics State University of New York at Albany, June 02-06, 1987. PMID- 22670785 TI - Peripherally circulating CD4+ FOXP3+ CXCR3+ T regulatory cells correlate with renal allograft function. AB - Peripheral immunoregulation depends on T regulatory cell trafficking into the allograft to modulate the local alloresponse. Little is known about the relevance of trafficking receptors for Tregs after solid organ transplantation in humans. In this study, expression of the peripheral chemokine receptors CXCR3 and CCR5 on CD4+ FOXP3+ Treg cells was analysed and correlated with allograft function in renal transplant recipients. Flow cytometry analysis of peripheral blood mononuclear cells of 54 renal transplant recipients receiving a calcineurin inhibitor-based immunosuppression was performed for CD4, CD25, FOXP3, CXCR3 and CCR5 within the first 18 months post-transplantation. Correlation analysis of chemokine receptor expression and glomerular filtration rate as calculated by MDRD (eGFR) was performed. Expression of the peripheral homing receptors CXCR3 (r = 0.44, P < 0.05) and CCR5 (r = 0.45, P < 0.05) on FOXP3+ Tregs correlated with renal allograft function (eGFR) in patients receiving tacrolimus (n = 28), but not cyclosporine A (CsA) (n = 26). CsA but not tacrolimus reduced surface expression of CXCR3 on FOXP3+ Tregs in renal transplant recipients as correlated to trough levels (r = -0.42, P < 0.05). In contrast to CD4+ CXCR3+ CD25(lo) T cells, flow-sorted CD4+ CXCR3+ CD25(hi) Tregs isolated from healthy individuals did not produce IFNgamma or IL-17 ex vivo and expressed high levels of GARP mRNA both at baseline as well as after TCR activation indicating functional regulatory activity. Expression of the peripheral trafficking receptors CXCR3 and CCR5 on FOXP3+ Tregs is associated with renal allograft function. These results suggest that Treg trafficking may also depend on the interaction of CXCR3 or CCR5 and their respective ligands. PMID- 22670790 TI - Upcoming New Feature in the Journal of Biomolecular Structure & Dynamics. PMID- 22670786 TI - Primary mucinous carcinoma of the skin in the hypogastric region: a case of regional lymph node metastases 2 years after surgery. PMID- 22670792 TI - Palladium-catalyzed alkenylation and alkynylation of ortho-C(sp2)-H bonds of benzylamine picolinamides. AB - An efficient functionalization of ortho-C(sp(2))-H bonds of picolinamide (PA) protected benzylamine substrates with a range of vinyl iodides as well as acetylenic bromide is reported. ortho-Phenyl benzoic acid (oPBA) acts as an effective promoter in this reaction system. This method provides a practical strategy to access highly functionalized benzylamine compounds for organic synthesis. PMID- 22670793 TI - Covalent immobilization of trypsin on glutaraldehyde-activated silica for protein fragmentation. AB - Trypsin was immobilized by covalent binding to glutaraldehyde-activated silica with and without a spacer arm; 1,6-diaminohexane and polyethyleneglycol as well. The addition of polyethyleneglycol (PEG) to the immobilization media increased the activity of immobilized trypsin in organic solvents, whilst free trypsin activity disappeared under the same conditions. Thermal, pH, storage, and operational stabilities of the free and immobilized enzyme were found to be better than the free enzyme. Furthermore, use of immobilized enzyme for protein fragmentation was achieved by solid-phase, on-line, protein digestion in organic solvents. Reaction times were reduced to a few minutes and the sample handling was minimized. PMID- 22670795 TI - Where are the men? Targeting male partners in preventing mother-to-child HIV transmission. AB - Involvement of male partners may increase adherence to and improve outcomes of programs to prevent mother-to-child HIV transmission (PMTCT). Greater understanding of factors impeding male voluntary HIV counseling and testing (VCT) is needed. A cross-sectional study was conducted in Tshwane, South Africa. Semi structured interviews were completed with men whose partners had recently been pregnant. Of 124 men who participated, 94% believed male HIV testing was important, but 40% had never been tested. Of those tested, 32% were tested during the pregnancy, while 37% were tested afterward. Fifty-eight percent of men reported that their female partners had disclosed their test results during pregnancy. A man's likelihood of testing during pregnancy was associated with prior discussion of testing in PMTCT, knowing the female partner had tested, and her disclosure of the test result (all p<0.05). In terms of increasing male partner HIV testing rates, 74% of the men reported they would respond favorably to a written invitation for VCT from their partners. Based on themes that emerged during the interviews, six partner invitation cards to encourage male involvement in PMTCT were designed. Responses to the cards were elicited from 158 men and 409 women. One invitation card framed by the themes of fatherhood and the baby was selected by 41% of men and 31% of women as the most likely for women undergoing PMTCT to bring to their male partners and the most successful at encouraging men to be tested. In conclusion, this study found that a substantial proportion of men whose partners were recently pregnant had never been tested themselves; of those who had tested, most had done so only after the pregnancy. Encouraging partner communication and clinic attendance using an invitation card could facilitate increased male testing and participation in PMTCT. PMID- 22670794 TI - Is the cardiovascular system a therapeutic target for cannabidiol? AB - Cannabidiol (CBD) has beneficial effects in disorders as wide ranging as diabetes, Huntington's disease, cancer and colitis. Accumulating evidence now also suggests that CBD is beneficial in the cardiovascular system. CBD has direct actions on isolated arteries, causing both acute and time-dependent vasorelaxation. In vitro incubation with CBD enhances the vasorelaxant responses in animal models of impaired endothelium-dependent vasorelaxation. CBD protects against the vascular damage caused by a high glucose environment, inflammation or the induction of type 2 diabetes in animal models and reduces the vascular hyperpermeability associated with such environments. A common theme throughout these studies is the anti-inflammatory and anti-oxidant effect of CBD. In the heart, in vivo CBD treatment protects against ischaemia-reperfusion damage and against cardiomyopathy associated with diabetes. Similarly, in a different model of ischaemia-reperfusion, CBD has been shown to reduce infarct size and increase blood flow in animal models of stroke, sensitive to 5HT(1A) receptor antagonism. Although acute or chronic CBD treatment seems to have little effect on haemodynamics, CBD reduces the cardiovascular response to models of stress, applied either systemically or intracranially, inhibited by a 5HT(1A) receptor antagonist. In blood, CBD influences the survival and death of white blood cells, white blood cell migration and platelet aggregation. Taken together, these preclinical data appear to support a positive role for CBD treatment in the heart, and in peripheral and cerebral vasculature. However, further work is required to strengthen this hypothesis, establish mechanisms of action and whether similar responses to CBD would be observed in humans. PMID- 22670796 TI - Conflict adaptation: it is not what you expect. AB - In two studies, a vocal Stroop task with eight different colours was employed in order to put two core assumptions of the original interpretation of the Gratton effect to the test. We verified whether top-down control processes can elicit conflict adaptation when episodic memory effects are controlled for and to what extent proactive adjustments driven by the subjects' expectancy for congruency level repetition contribute to this effect. Therefore, we presented Stroop stimuli without feature repetitions and investigated whether the induced expectancy manipulation of raising the amount of either congruency level repetitions or alternations in a training phase transferred to an unmanipulated test phase. Over the two experiments, a sequential modulation of the Stroop effect was found in the absence of stimulus feature repetitions, strongly confirming a share for top-down control processes in bringing about the Gratton effect. In the condition where congruency level repetitions were raised, a strong Gratton effect was found. When congruency level alternations outnumbered repetitions, the Gratton effect disappeared completely. However, this difference seemed mainly due to cumulative effects of local, dynamic, trial-to-trial control adjustments rather than expectancy-induced attentional shifting. Once the transition probability changed back to 50% in the test phase of each experiment, a similar Gratton effect was found in both conditions. Taken together, these results are best explained in terms of dynamic reactive control. PMID- 22670797 TI - Preformulation and formulation of newly synthesized QNT3-18 for development of a skin whitening agent. AB - New molecules having the structure of (E)-2-(4-tert-butylbenzylidene) hydrazinecarbothioamide (QNT3-18) or 4-tert-butylphenylthiourea (QNT3-20) was synthesized and presupposed to inhibit melanogenesis through the inhibition of tyrosinase, which is involved in melanin formation. Therefore, we seek to develop these new molecules as skin whitening agents in topical formulations based on preformulation studies. QNT3-18 or QNT3-20 showed a strong single endothermic peak at 159.34 degrees C with 10.79 MUm-sized or at 150.69 degrees C with 9.0 MUm sized aggregated particles, respectively. Both QNT3-18 and QNT3-20 did not show cytotoxicity at effective concentration range (0.4 uM) against keratinocyte cells and QNT3-18 was more retained than QNT3-20 in the skin instead of permeating through the skin. QNT3-18 or QNT3-20 was practically insoluble in water; the aqueous solubility was 3.8 +/- 0.37 or 130.6 +/- 2.52 MUg/mL, respectively. Also, the partition coefficient value (log P) corresponding to the quotient between aqueous and octanol concentration of the molecule was 3.9 or 2.6, respectively. The skin retention amount of QNT3-18 was 1.7-fold higher than that of QNT3-20. When the optimal SLN cream (J3 formulation) containing 4 MUM QNT3-18 was applied on the backs of hairless rats for 4 days after UV irradiation for 7 days and the skin color was checked by reflectance spectrophotometer, the rat skin treated with SLN cream with QNT3-18 quickly recovered to normal compared to skin treated with SLN cream without QNT3-18. Taken together, this study suggests that topical formulations such as creams including SLNs with QNT3-18 might be appropriate carriers for skin whitening agents. PMID- 22670798 TI - Potentially curative treatment in patients with hepatocellular cancer--results from the liver cancer research network. AB - BACKGROUND: The extent to which potentially curative therapies are used in patients with hepatocellular cancer (HCC) and their related outcomes are unknown in the US. AIM: To determine the rate and outcomes of potentially curative treatment in patients with HCC. METHODS: Eleven US centers followed patients with HCC between 2001 and 2007. We determined rates of liver transplantation, surgical resection, or tumour ablation during follow-up, examined differences in adjusted survival of patients receiving these treatments, and determined the factors associated with receipt of potentially curative treatment. RESULTS: Of the 267 patients, 76 (28%) patients had early HCC, defined as Child A or B cirrhosis, with a solitary HCC or <= 3 nodules, each <= 3 cm. Of these, 53 (69.7%) received curative treatment. Thirty six percent of patients with non-early HCC received curative treatment. Compared to patients with non-early HCC who did not receive curative treatment, patients with early HCC and curative treatment had the best survival [hazard ratio, HR = 0.19 (95% CI, 0.08-0.42)] followed by patients with advanced HCC who received curative treatment [HR = 0.37 (95% CI, 0.22-0.64)]. Baseline performance status was significantly associated with receipt of curative treatment as well as survival after adjusting for demographics, clinical characteristics, and HCC stage. CONCLUSIONS: In this multicenter database, most of the patients with early HCC received potentially curative treatment. However, only 28% of patients had early HCC. One-third of patients with non-early HCC also underwent curative therapy. Potentially curative treatment improved survival and this effect was seen in patients with early as well as non-early HCC. PMID- 22670799 TI - A direct route to bis(imido)uranium(V) halides via metathesis of uranium tetrachloride. AB - Metathesis reactions between uranium tetrachloride and lithium 2,6 diisopropylphenylamide in the presence of 4,4'-dialkyl-2,2'-bipyridyl (R(2)bpy; R = Me, (t)Bu) or triphenylphosphine oxide (tppo) appear to generate bis(imido)uranium(IV) in situ. These extremely reactive complexes abstract chloride from dichloromethane to generate U(NDipp)(2)Cl(R(2)bpy)(2) or U(NDipp)(2)Cl(tppo)(3) (Dipp = 2,6-(i)Pr(2)C(6)H(3)). The preparation of the bromide and iodide analogues U(NDipp)(2)X(R(2)bpy)(2) was achieved by addition of CH(2)X(2) (X = Br, I) to the uranium(IV) solutions. The uranium(V) halides were characterized by X-ray crystallography and found to exhibit linear N-U-N units and short U-N bonds. Electrochemical measurements were made on the chloride bipyridine species, which reacts readily with iodine or ferrocenium to generate bis(imido)uranium(VI) cations. PMID- 22670800 TI - Potential effects of tooth-brushing on human dentin wear following exposure to acidic soft drinks. AB - This study used scanning electron microscopy and atomic force microscopy to examine the short-term potential effects of brushing time and the start-time of tooth-brushing after demineralization on primary dentin wear in vitro. Thirty-six noncarious primary central incisors were assigned to 12 experimental groups. Exposure to cola drinks was used to initiate the demineralization process. Three brushing times (5, 15 and 30 s) and four start-times of brushing (0, 30, 60 and 120 min) after an erosive attack were used for the abrasion process. Tooth brushing the softened dentin surface led to increases in the open tubular fraction and microstructural changes on the dentin surface. Brushing immediately after exposure to cola resulted in the greatest irreversible dentin loss, whereas brushing 60 or 120 min after pretreatment resulted in the least irreversible dentin loss. However, brushing time had no effect on the irreversible loss of dentin wear. Based on these experimental results, tooth-brushing should be performed at least 60 min after consuming a cola drink to achieve the desired tooth cleaning and avoid the introduction of surface lesions on dentin. PMID- 22670801 TI - A new technique for percutaneous dilatational tracheostomy (G-Trach): preliminary experience in pigs. AB - Tracheostomies are currently used for airway management in patients requiring long-term respiratory assistance. The dilatational percutaneous technique of forming tracheostomies is a valuable alternative to traditional surgical 'open' techniques. In this study, we tested a new dilatational percutaneous tracheostomy device using a balloon dilator with a particular innovative shape (G-Trach). At the Autonomous University of Barcelona Veterinary Institute, eight pigs (weighing 20-40 kg) were anaesthetised and underwent tracheostomy using the novel G-Trach technique. The mean (SD) procedure time was 2.63 (0.64) min from tracheal puncture to ventilation through the tracheostomy tube, and the mean (SD) time from positioning the dilator balloon to introducing the cannula was 0.71 (0.38) min. Vital functions and oxygen saturation remained constant throughout the procedures. Postmortem examinations did not reveal any tracheal injury. The G Trach seems to be a safe and easy new dilatational percutaneous technique for forming tracheostomies. The minimal subcutaneous tissue dissection could potentially decrease complications when compared with standard dilatational percutaneous tracheostomy methods. To confirm this hypothesis a human trial is ongoing. PMID- 22670802 TI - Cardiovascular effects of green tea catechins: progress and promise. AB - Recently, there is a growing interest in the cardiovascular beneficial effects of green tea. Epidemiological and clinical studies have suggested that consumption of green tea is inversely associated with the risk of developing cardiovascular diseases. Catechins, the major flavonoid constituents of green tea, exert cardioprotective effects through diverse mechanisms that include reversal of endothelial dysfunctions, decreasing inflammatory biomarkers, and providing antioxidant, antiplatelet and antiproliferative effects. Moreover, dietary consumption of green tea catechins has beneficial effects on blood pressure and lipid parameters. This review will focus on discussing the latest research on the cardioprotective effects of green tea catechins and their underlying molecular mechanisms. Several recent patents pertinent to green tea and cardiovascular health will also be discussed. It is noteworthy that clinical studies involving green tea are fraught with multiple complexity and confounding factors. Therefore, a rigorous assessment of the effects of green tea catechins in well controlled human trials will be required for better understanding of the effects of green tea in cardiovascular health. PMID- 22670803 TI - Evaluation of clinical efficacy of fasudil for the treatment of pulmonary arterial hypertension. AB - Multiple cell types in the vascular wall rely upon the rho-kinase (ROCK) signaling pathway for homeostatic function and response to injury. These cell types include endothelial and vascular smooth muscle cells, inflammatory cells, and fibroblasts. Rho is a guanosine triphosphate binding protein that activates its downstream target rho-kinase, in response to activation of a variety of G protein coupled receptors. When activated, ROCK inhibits myosin phosphatase and conversely upregulates the ezrin-radixin-moesin family of kinases. In vitro activation of these signaling cascades results in modulation of multiple cellular processes, including enhanced vasoconstriction, proliferation, impaired endothelial response to vasodilators, chronic pulmonary remodeling, and upregulation of vasoactive cytokines via the NF-kappaB transcription pathway. ROCK activity has also been linked specifically to a number of known effectors of pulmonary arterial hypertension (PAH), including endothelin-1, serotonin, and endothelial nitric oxide synthase, among others. Recently, elevated ROCK activity has been demonstrated in various animal models of PAH with ROCK inhibitors associated with pulmonary vasodilatation and regression of PAH. ROCK inhibitors are a new class of agents which may be beneficial in the treatment of PAH. Fasudil (Daiichi Chemical and Pharmacological Company, Ibaragi, Japan), a first generation ROCK inhibitor, has been widely studied. Emerging evidence from both animal and human studies suggests that fasudil can promote vasodilation independent of the mechanism that induces vasoconstriction and will be useful in conditions in which endothelial function is impaired including PAH. Several recent patents have described fasudil as a potential therapeutic option in PAH. This article provides an overview of the role of ROCK in the pathogenesis of PAH and discusses the clinical efficacy of fasudil as a therapeutic option for treating PAH. PMID- 22670804 TI - Increasing cotton genome coverage with polymorphic SSRs as revealed by SSCP. AB - Simple sequence repeat (SSR) markers are widely used in plant genetics and breeding. However, there are many SSR markers that do not reveal polymorphism in cotton. Traditional SSR genotyping methods only provide information on product sizes. This leaves many marker polymorphism undetected, thus, lowering the utility of SSRs. In the present study, monomorphic SSRs between two mapping parents, 'Emian22' and 3-79, were subjected to single-strand conformation polymorphism (SSCP) analysis to reveal polymorphism. Of the 4194 monomorphic SSR primer pairs, 158 pairs (3.77%) showed polymorphism and revealed 174 polymorphic loci. Sequence analysis showed that the differences in PCR products between the mapping parents were solely due to base transition or transversion, which was in agreement with SSCP principles. SSCP also revealed SSRs with motifs of AT/TA and GAA/CTT were more polymorphic in dinucleotides and trinucleotides, respectively. Genetic mapping integrated 160 loci into our interspecific BC(1) linkage map, 5 of which associated with QTLs related to cotton fiber quality. The technique discussed in the present study enables us to detect polymorphism of monomorphic SSRs, and increase the utilization efficiency of the existing SSR primers. PMID- 22670805 TI - LDL apheresis and inflammation--implications for atherosclerosis. AB - Low-density lipoprotein (LDL) apheresis is an extracorporeal treatment modality used in high-risk patients when LDL cholesterol levels cannot be reduced adequately with medication. The treatment is highly effective, but could be affected by potential unwanted effects on pro- and anti-inflammatory biomarkers. In this paper, we review the literature regarding the effect of LDL apheresis on pro- and anti-inflammatory biomarkers important in atherosclerosis, also as patients in LDL apheresis have high risk for atherosclerotic complications. We discuss the effect of LDL apheresis on complement, cytokines and finally a group of other selected pro- and anti-inflammatory biomarkers. The complement system is affected by LDL apheresis, and there are differences between different LDL apheresis systems. The plasma separation columns seem to trigger the formation of proinflammatory complement factors including C3a and C5a, while the same anaphylatoxins are adsorbed by the LDL apheresis columns, however, to varying degree. Proinflammatory cytokines are to some extent adsorbed by the LDL apheresis columns, while some of the anti-inflammatory cytokines increase during treatment. Finally, we discuss the effect of apheresis on different biomarkers including C-reactive protein, fibrinogen, adhesion molecules, myeloperoxidase and HDL cholesterol. In conclusion, even if there are differences between pro- and anti-inflammatory biomarkers during LDL apheresis, the consequences for the patients are largely unknown and larger studies need to be performed. Preferably, they should be comparing the effect of different LDL apheresis columns on the total inflammatory profile, and this should be related to clinical endpoints. PMID- 22670807 TI - Water-soluble conjugated polymers for imaging, diagnosis, and therapy. PMID- 22670806 TI - The patient-centered medical home and patient experience. AB - OBJECTIVE: To examine the relationship between practices' reported use of patient centered medical home (PCMH) processes and patients' perceptions of their care experience. DATA SOURCE: Primary survey data from 393 physician practices and 1,304 patients receiving care in those practices. STUDY DESIGN: This is an observational, cross-sectional study. Using standard ordinary least-squares and a sample selection model, we estimated the association between patients' care experience and the use of PCMH processes in the practices where they receive care. DATA COLLECTION: We linked data from a nationally representative survey of individuals with chronic disease and two nationally representative surveys of physician practices. PRINCIPAL FINDINGS: We found that practices' use of PCMH processes was not associated with patient experience after controlling for sample selection as well as practice and patient characteristics. CONCLUSIONS: In our study, which was large, but somewhat limited in its measures of the PCMH and of patient experience, we found no association between PCMH processes and patient experience. The continued accumulation of evidence related to the possibilities of the PCMH, how PCMH is measured, and how the impact of PCMH is gauged provides important information for health care decision makers. PMID- 22670808 TI - Optimization of primaquine diphosphate tablet formulation for controlled drug release using the mixture experimental design. AB - A tablet formulation based on hydrophilic matrix with a controlled drug release was developed, and the effect of polymer concentrations on the release of primaquine diphosphate was evaluated. To achieve this purpose, a 20-run, four factor with multiple constraints on the proportions of the components was employed to obtain tablet compositions. Drug release was determined by an in vitro dissolution study in phosphate buffer solution at pH 6.8. The polynomial fitted functions described the behavior of the mixture on simplex coordinate systems to study the effects of each factor (polymer) on tablet characteristics. Based on the response surface methodology, a tablet composition was optimized with the purpose of obtaining a primaquine diphosphate release closer to a zero order kinetic. This formulation released 85.22% of the drug for 8 h and its kinetic was studied regarding to Korsmeyer-Peppas model, (Adj-R(2) = 0.99295) which has confirmed that both diffusion and erosion were related to the mechanism of the drug release. The data from the optimized formulation were very close to the predictions from statistical analysis, demonstrating that mixture experimental design could be used to optimize primaquine diphosphate dissolution from hidroxypropylmethyl cellulose and polyethylene glycol matrix tablets. PMID- 22670809 TI - Structural and kinetic analysis of prolyl-isomerization/phosphorylation cross talk in the CTD code. AB - The C-terminal domain (CTD) of eukaryotic RNA polymerase II is an essential regulator for RNA polymerase II-mediated transcription. It is composed of multiple repeats of a consensus sequence Tyr(1)Ser(2)Pro(3)Thr(4)Ser(5)Pro(6)Ser(7). CTD regulation of transcription is mediated by both phosphorylation of the serines and prolyl isomerization of the two prolines. Interestingly, the phosphorylation sites are typically close to prolines, and thus the conformation of the adjacent proline could impact the specificity of the corresponding kinases and phosphatases. Experimental evidence of cross-talk between these two regulatory mechanisms has been elusive. Pin1 is a highly conserved phosphorylation-specific peptidyl-prolyl isomerase (PPIase) that recognizes the phospho-Ser/Thr (pSer/Thr)-Pro motif with CTD as one of its primary substrates in vivo. In the present study, we provide structural snapshots and kinetic evidence that support the concept of cross-talk between prolyl isomerization and phosphorylation. We determined the structures of Pin1 bound with two substrate isosteres that mimic peptides containing pSer/Thr-Pro motifs in cis or trans conformations. The results unequivocally demonstrate the utility of both cis- and trans-locked alkene isosteres as close geometric mimics of peptides bound to a protein target. Building on this result, we identified a specific case in which Pin1 differentially affects the rate of dephosphorylation catalyzed by two phosphatases (Scp1 and Ssu72) that target the same serine residue in the CTD heptad repeat but have different preferences for the isomerization state of the adjacent proline residue. These data exemplify for the first time how modulation of proline isomerization can kinetically impact signal transduction in transcription regulation. PMID- 22670810 TI - The influence of bleeding on trigger changes for platelet transfusion in patients with chemotherapy-induced thrombocytopenia. AB - BACKGROUND: For patients with thrombocytopenia without bleeding risk factors, a platelet transfusion trigger of 10 * 10(9) /L is recommended. No studies have evaluated the clinicians' decision-making process leading to trigger changes. STUDY DESIGN AND METHODS: We report on the evaluation of trigger changes and the relation with bleeding. Eighty patients previously enrolled in the SPRINT trial represent the patient population for the current analysis. RESULTS: Seventy-four patients had a starting trigger of 10 * 10(9) /L. Only a minority of patients treated with chemotherapy alone (3/12, 25%) and autologous transplant (6/15, 40%) had a change in their trigger in contrast to the majority of allogeneic transplant (37/47, 79%; p = 0.001 and p = 0.009, respectively, when compared to allogeneic transplant group). Bleeding was the main reason reported by clinicians for a trigger change, but the occurrence of significant bleeding (Grade 2-4) was similar in patients with or without a trigger change (51 and 54%, p = 1.00). Clinicians were influenced by the bleeding system: grade 1 mucocutaneous bleeding leading to a trigger change was overrepresented (71% of cases), as was grade 2 genitourinary bleeding not leading to a trigger change (57% of cases). CONCLUSION: A universal trigger of 10 * 10(9) /L may not be maintained in a diverse population of patients with their respective bleeding risk factors. Because the trigger is changed often, it may not be as effective as previously believed. PMID- 22670811 TI - Late-onset papular eruption after the initial course of combination chemotherapy consisting of paclitaxel and carboplatin: report of two cases. PMID- 22670812 TI - Dr. Rene Favaloro. PMID- 22670814 TI - The dynamic nature of bud dormancy in trees: environmental control and molecular mechanisms. AB - In tree species native to temperate and boreal regions, the activity-dormancy cycle is an important adaptive trait both for survival and growth. We discuss recent research on mechanisms controlling the overlapping developmental processes that define the activity-dormancy cycle, including cessation of apical growth, bud development, induction, maintenance and release of dormancy, and bud burst. The cycle involves an extensive reconfiguration of metabolism. Environmental control of the activity-dormancy cycle is based on perception of photoperiodic and temperature signals, reflecting adaptation to prevailing climatic conditions. Several molecular actors for control of growth cessation have been identified, with the CO/FT regulatory network and circadian clock having important coordinating roles in control of growth and dormancy. Other candidate regulators of bud set, dormancy and bud burst have been identified, such as dormancy associated MADS-box factors, but their exact roles remain to be discovered. Epigenetic mechanisms also appear to factor in control of the activity-dormancy cycle. Despite evidence for gibberellins as negative regulators in growth cessation, and ABA and ethylene in bud formation, understanding of the roles that plant growth regulators play in controlling the activity-dormancy cycle is still very fragmentary. Finally, some of the challenges for further research in bud dormancy are discussed. PMID- 22670816 TI - Theoretical Biochemistry & Molecular Biophysics. PMID- 22670815 TI - Improved protocol for indoline synthesis via palladium-catalyzed intramolecular C(sp2)-H amination. AB - An efficient method has been developed for the synthesis of indoline compounds from picolinamide (PA)-protected beta-arylethylamine substrates via palladium catalyzed intramolecular amination of ortho-C(sp(2))-H bonds. These reactions feature high efficiency, low catalyst loadings, mild operating conditions, and the use of inexpensive reagents. PMID- 22670817 TI - RELATED ADENINE TITLES. PMID- 22670819 TI - Instructions to Author. PMID- 22670822 TI - MOLECULAR MODELLER. PMID- 22670820 TI - Seventh Conversation in the Discipline Biomolecular Stereodynamics State University of New York at Albany, June 18-22, 1991. PMID- 22670823 TI - The organization of conspecific face space in nonhuman primates. AB - Humans and chimpanzees demonstrate numerous cognitive specializations for processing faces, but comparative studies with monkeys suggest that these may be the result of recent evolutionary adaptations. The present study utilized the novel approach of face space, a powerful theoretical framework used to understand the representation of face identity in humans, to further explore species differences in face processing. According to the theory, faces are represented by vectors in a multidimensional space, the centre of which is defined by an average face. Each dimension codes features important for describing a face's identity, and vector length codes the feature's distinctiveness. Chimpanzees and rhesus monkeys discriminated male and female conspecifics' faces, rated by humans for their distinctiveness, using a computerized task. Multidimensional scaling analyses showed that the organization of face space was similar between humans and chimpanzees. Distinctive faces had the longest vectors and were the easiest for chimpanzees to discriminate. In contrast, distinctiveness did not correlate with the performance of rhesus monkeys. The feature dimensions for each species' face space were visualized and described using morphing techniques. These results confirm species differences in the perceptual representation of conspecific faces, which are discussed within an evolutionary framework. PMID- 22670824 TI - Parent-child exome sequencing identifies a de novo truncating mutation in TCF4 in non-syndromic intellectual disability. PMID- 22670825 TI - In vitro effect of novel beta-lactam compounds on xanthine oxidase enzyme activity. AB - Carbazole substituted imines (2a-l) were prepared from N-methyl-3-amino carbazole with different aldehydes. The imines compounds undergo (2+2) cycloaddition reactions with in situ ketenes to produce beta-lactam compounds (3a-l). The beta lactam compounds were tested as inhibitors of the xanthine oxidase (XO) purified from bovine milk. The results show that these compounds exhibit inhibitory effects on XO at low concentrations with IC(50) values ranging from 21.65 to 58.04 uM. The most effective compound for XO was 4-(4-chlorophenyl)-1-(9-ethyl-9H carbazol-3-yl)-3-phenylazetidin-2-one with IC(50) of 21.65 MUM. The lactams investigated here showed effective XO inhibitory effects, in the same range as the clinically used allopurinol. PMID- 22670827 TI - A randomised comparison of the self-pressurised air-QTM intubating laryngeal airway with the LMA UniqueTM in children. AB - We conducted a randomised trial comparing the self-pressurised air-QTM intubating laryngeal airway (air-Q SP) with the LMA-Unique in 60 children undergoing surgery. Outcomes measured were airway leak pressure, ease and time for insertion, fibreoptic examination, incidence of gastric insufflation and complications. Median (IQR [range]) time to successful device placement was faster with the air-Q SP (12 (10-15 [5-18])) s than with the LMA-Unique (14 (12 17 [6-22]) s; p=0.05). There were no statistically significant differences between the air-Q SP and LMA-Unique in initial airway leak pressures (16 (14-18 [10-29]) compared with 18 (15-20 [10-30]) cmH2 O, p=0.12), an airway leak pressures at 10 min (19 (16-22 [12-30]) compared with 20 (16-22 [10-30]) cmH2 O, p=0.81); fibreoptic position, incidence of gastric insufflation, or complications. Both devices provided effective ventilation without the need for airway manipulation. The air-Q SP is an alternative to the LMA-Unique should the clinician prefer a device not requiring cuff monitoring during anaesthesia. PMID- 22670826 TI - Effects of spray drying process parameters on the solubility behavior and physical stability of solid dispersions prepared using a laboratory-scale spray dryer. AB - PURPOSE: The purpose of this study is to determine the process parameters of the laboratory-scale spray dryer affecting the solubility behavior and physical stability of solid dispersions. METHODS: Solid dispersions of the model drug (nilvadipine or nifedipine) and hypromellose (HPMC) (w/w: 1/1) were prepared using the laboratory-scale spray dryer. As process parameters, nitrogen flow rate, sample concentration and pump speed were investigated. The samples were characterized by dissolution tests, powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), scanning electron microscope (SEM), and nanoscale thermal analysis (Nano-TA). The physical stability was monitored after 7 months storage at 25 degrees C. RESULTS: Solubility behavior and physical stability were improved by setting the low nitrogen flow rate and high sample concentration. DSC showed that the physical state depends on the spray drying conditions, whereas, every sample showed the similar morphology from SEM results. The difference of solubility behavior and physical stability were found to come from the microstructural phase separation of the spray dried particles using a novel analytical technique (Nano-TA). CONCLUSIONS: This study demonstrated that nitrogen flow rate and sample concentration should be the critical parameters for the enhancements of the solubility and physical stability of solid dispersions. PMID- 22670828 TI - Approach to the synthesis of indoline derivatives from diaryliodonium salts. AB - An effective method of constructing the indoline moiety via intramolecular nucleophilic ring closure of a diaryliodonium salt is described. Diacetoxyiodoarene compounds (1a-1e) were converted into intermediate Koser's reagent and coupled with arylstannanes (7-10) to form diaryliodonium salts (11a 14e). Indoline compounds with different N-protecting groups, 15, 16, 17, and 18, were synthesized in higher yields by treating salts (11a-14e) with Cs(2)CO(3) and TEMPO. Regardless of the electronic environment of five para-substituted iodoarenes and the natures of four N-protected arylstannane groups, the conversion proceeded well to afford corresponding indolines in yields of 72-84 and 70-84%, respectively. PMID- 22670829 TI - Novel gold-capped nanopillars imprinted on a polymer film for highly sensitive plasmonic biosensing. AB - Herein, a nanoporous alumina was fabricated to use as a mold in transforming nanopillar structures onto a thin film polymer by thermal nanoimprint lithography (NIL). The size of the pores was successfully controlled by varying the applied voltages and etching time. These nanoporous structures were transferred to the Cyclo-olefin polymer (COP) film surface from the porous mold by a thermal nanoimprinting process. A plasmonic substrate was fabricated by sputtering a thin layer of gold onto this nanopillar polymer structure, and the refractive index response in a variety of media was evaluated. Finally, the biosensing capacity of this novel plasmonic substrate was verified by analysis of Human immunoglobulin and achieved a minimum detection limit of 1.0 ng/mL. With the advantages of mass production with consistent reproducibility stemming from the nanoimprint fabrication process, our gold-capped polymeric pillars are ready for the transition from academic interest into commercialization systems for practical use in diagnostic applications. PMID- 22670831 TI - Carbon monoxide activation via O-bound CO using decamethylscandocinium hydridoborate ion pairs. AB - Ion pairs [Cp*(2)Sc](+)[HB(p-C(6)F(4)R)(3)](-) (R = F, 1-F; R = H, 1-H) were prepared and shown to be unreactive toward D(2) and alpha-olefins, leading to the conclusion that no back-transfer of hydride from boron to scandium occurs. Nevertheless, reaction with CO is observed to yield two products, both ion pairs of the [Cp*(2)Sc](+) cation with formylborate (2-R) and borataepoxide (3-R) counteranions. DFT calculations show that these products arise from the carbonyl adduct of the [Cp*(2)Sc](+) in which the CO is bonded to scandium through the oxygen atom, not the carbon atom. The formylborate 2-R is formed in a two-step process initiated by an abstraction of the hydride by the carbon end of an O bound CO, which forms an eta(2)-formyl intermediate that adds, in a second step, the borane at the carbon. The borataepoxide 3-R is suggested to result from an isomerization of 2-R. This unprecedented reaction represents a new way to activate CO via a reaction channel emanating from the ephemeral isocarbonyl isomer of the CO adduct. PMID- 22670830 TI - Assessment of potential drug interactions by characterization of human drug metabolism pathways using non-invasive bile sampling. AB - AIM: Characterization of the biliary disposition of GSK1325756, using a non invasive bile sampling technique and spectrometric analyses, to inform the major routes of metabolic elimination and to enable an assessment of victim drug interaction risk. METHOD: Sixteen healthy, elderly subjects underwent non invasive bile capture using a peroral string device (Entero-Test((r))) prior to and following a single oral dose of GSK1325756 (100 mg). The device was swallowed by each subject and once the weighted string was judged to have reached the duodenum, gallbladder contraction was stimulated in order to release bile. The string was then retrieved via the mouth and bile samples were analyzed for drug related material using spectrometric and spectroscopic techniques following solvent extraction. RESULTS: Nuclear magnetic resonance spectroscopy (NMR) indicated that the O-glucuronide metabolite was the major metabolite of GSK1325756, representing approximately 80% of drug-related material in bile. As bile is the major clearance route for GSK1325756 (only 4% of the administered dose was excreted in human urine), this result indicates that uridine 5' diphospho-glucuronosyltransferases (UGTs) are the major drug metabolizing enzymes responsible for drug clearance. The relatively minor contribution made by oxidative routes reduces the concern of CYP-mediated victim drug interactions. CONCLUSION: The results from this study demonstrate the utility of deploying the Entero-Test(r) in early human studies to provide information on the biliary disposition of drugs and their metabolites. This technique can be readily applied in early clinical development studies to provide information on the risk of interactions for drugs that are metabolized and eliminated in bile. PMID- 22670832 TI - Action of tyrosinase on ortho-substituted phenols: possible influence on browning and melanogenesis. AB - The action of tyrosinase on ortho-substituted monophenols (thymol, carvacrol, guaiacol, butylated hydroxyanisole, eugenol, and isoeugenol) was studied. These monophenols inhibit melanogenesis because they act as alternative substrates to L tyrosine and L-Dopa in the monophenolase and diphenolase activities, respectively, despite the steric hindrance on the part of the substituent in ortho position with respect to the hydroxyl group. We kinetically characterize the action of tyrosinase on these substrates and assess its possible effect on browning and melanognesis. In general, these compounds are poor substrates of the enzyme, with high Michaelis constant values, K(m), and low catalytic constant values, k(cat), so that the catalytic efficiency k(cat)/K(m) is low: thymol, 161 +/- 4 M(-1) s(-1); carvacrol, 95 +/- 7 M(-1) s(-1); guaiacol, 1160 +/- 101 M(-1) s(-1). PMID- 22670833 TI - The influence of 'cognitive busyness' on causal attributions of challenging behaviour in dementia: a preliminary experimental study. AB - This study investigated the influence of 'cognitive busyness' (competing cognitive demands) on residential care staff attributions of challenging behaviour (CB) related to dementia. Following the model of attribution formation proposed by Gilbert, Pelham, and Krull (1988), it was hypothesised that care staff experiencing competing cognitive demands at the time of observing CBs linked with dementia would be more likely to make internal and controllable attributions regarding the causes of such behaviour. This study employed a cross over experimental design. Thirty formal dementia care-workers viewed two video clips of simulated CB, one under conditions of cognitive 'busyness' and another under control conditions of no extra cognitive demands. These conditions occurred a week apart and were counterbalanced, i.e. one group of participants undertook the control condition first and then the experimental condition whilst another undertook the reverse. Self-report measures of attributions were administered after the viewing of each video clip. Competing cognitive demands significantly influenced staff attributions regarding CB, in relation to internality and controllability, and type of CB emerged as a potential moderating factor. No link was found between cognitive busyness and other attributional dimensions (stability and globality). Concurrent cognitive demands seem capable of impairing the ability to use situational information to form some causal attributions regarding CB in dementia but this might depend on the type of CB being witnessed. The results are discussed in relation to key methodological and conceptual issues. PMID- 22670834 TI - Evaluation of HSPA2 in fertile and infertile individuals. AB - Heat-shock protein A2 (HSPA2) is a testis-specific member of the HSP70 family known to correlate with sperm maturity, function and fertility. The aim of this study was to compare expression of HSPA2 in fertile and infertile individuals using a recently marketed highly purified polyclonal antibody. Thus, after analysing sperm concentration, motility and morphology in semen sample of 49 individuals with male factor infertility and 47 fertile individuals according to World Health Organization guidelines, we evaluated HSPA2 by microscope florescence, flow cytometry, Western blot and RT-PCR. We observed higher percentage of sperm expressing HSPA2 in anterior and equatorial regions in fertile than infertile individuals by microscope fluorescence. Percentage of sperm expressing HSPA2 in two conditions (fixed permeabilised and capacitated) by flow cytometry showed that percentage of HSPA2-positive sperm in fixed permeabilised and also capacitated samples was significantly different between fertile and infertile individuals. Western blot analysis of HSPA2 in semen samples revealed high variation within the fertile and infertile population. The results of RT-PCR revealed higher expression of HSPA2 in the fertile compared to infertile individuals, but this difference was not significant. According to the results, we suggest that HSPA2 expression is heterogeneously expressed on different part of fixed permeabilised sperm and its expression is significantly higher in fertile compared to infertile individuals. The surface expression of this protein significantly increases following capacitation in both fertile and infertile individuals. HSPA2 expression significantly correlates with sperm concentration and morphology. Therefore, aberrant HSPA2 expression may play an important role in capacitation and fertilisation processes. PMID- 22670836 TI - Evaluation of imperfections in silica and chalcogenide glass microspheres using focussed ion beam milling and imaging. AB - Microspheres made from optical glasses such as silica and chalcogenide are used as both passive and active optical elements in micro-optics systems and devices. The homogeneity of the microspheres is crucial to their optical quality and performance in such devices and so it is essential, in optimizing such systems, that techniques with nanometer scale resolution are developed to measure the internal structure and homogeneity of such spheres. In this work an analytical protocol based on focussed ion beam milling, combined with secondary ion and secondary electron imaging, has been developed to study the internal homogeneity of glass microspheres. The results have shown that silica microspheres with diameters of three to five microns, fabricated by a sol-gel method, have internal inhomogeneities and voids that will lead to non-uniform optical properties. The FIB milling and imaging technique developed has been found to be a very useful method of studying such inhomogeneities, which have been proposed, but never previously observed, in glass microspheres. The FIB based technique has also been used on larger chalcogenide glass (Ga(2)S(3):La(2)S(3)) microspheres (diameter of order 70 microns) but no inhomogeneities have been observed at the spatial resolution of a few microns so far achieved for these larger microspheres. This study suggests that the FIB based milling and imaging technique may have potential for quantitative use in the measurement of morphological variations in such systems as well as in the study of aging processes in micron-sized glass spheres. PMID- 22670837 TI - How do we integrate thromboelastography with perioperative transfusion management? PMID- 22670838 TI - Novel compounds and drugs and recent patents in treating multidrug-resistant and extensively drug-resistant tuberculosis. AB - A number of recent studies revealed that successful treatment of the patients with MDR/XDR- TB was not achieved due to high resistant rates to many second-line drugs such as kanamycin and prothionamide including poor adherence of the lengthy treatment. Many new drugs and compounds such as benzothiazinones, meropenem, PA 824, isoflavonoids, rhein, PNU-100480, TMC207, SQ109, OPC-67683, AZD5847, and linezolid are currently in development pipeline. According to very few patents in new compounds and drugs against MDR/XDRMycobacterium tuberculosis bacilli have been currently introduced, so inventors must be encouraged to contribute to this area worldwide. PMID- 22670835 TI - Re-examining the significance of surgical volume to breast cancer survival and recurrence versus process quality of care in Taiwan. AB - OBJECTIVE: This study explored the association of surgical volume versus process quality with breast cancer survival and recurrence. DATA SOURCES/STUDY SETTING: Population-based cancer registration data and National Health Insurance claim data. STUDY DESIGN: This population-based study linked Taiwan's Cancer Database with Taiwan's National Health Insurance Database to collect data on all patients diagnosed with breast cancer in 2003-2004 who received surgical treatment. PRINCIPAL FINDINGS: This study included 6,396 female breast cancer patients, reported by 26 hospitals. After controlling for patient and provider characteristics, Cox's regression models did not reveal any association between a physician's surgical volume and breast cancer recurrence or survival, although hospital volume was marginally associated with positive 5-year recurrence (HR: 1.001, 95%CI: 1.000, 1.001). After controlling for hospital or physician volume of surgery, we found a significant association between quality of care and both 5 year survival and recurrence. Random effects were also identified between patients and providers based on 5-year survival and 5-year recurrence. CONCLUSIONS: Process quality of care was significantly more related to survival or recurrence than to surgical volume. The random effects found within hospital patient clustered data indicated that the effect of the clustered feature of this data should be considered when performing volume-outcome related studies. PMID- 22670839 TI - MicroRNAs in chondrogenesis, articular cartilage, and osteoarthritis: implications for tissue engineering. AB - Coordinated actions of various regulators, including morphogens are required for chondrogenesis and maintenance of articular cartilage function. Bone morphogenetic proteins, and related signaling molecules and transcription factors form a complex regulatory network. MicroRNAs (miRNAs) are noncoding small RNAs that negatively regulate the expression of downstream targets by repressing the translation or inducing the cleavage of messenger RNAs (mRNAs). Increasing evidence indicates that miRNAs are an integral part of the regulatory network in chondrocyte differentiation and cartilage function. The aim of this article is to review the progress in miRNA expression and target genes in cartilage differentiation, homeostasis, and in the pathobiology of osteoarthritis. The recent progress in miRNAs in cartilage has implications for tissue engineering. PMID- 22670840 TI - Neuroprotection by GDNF in the ischemic brain. AB - The glial cell line-derived neurotrophic factor (GDNF) was first identified as a survival factor for midbrain dopaminergic neurons, but additional studies provided evidences for a role as a trophic factor for other neurons of the central and peripheral nervous systems. GDNF regulates cellular activity through interaction with glycosyl-phosphatidylinositol-anchored cell surface receptors, GDNF family receptor-alpha1, which might signal through the transmembrane Ret tyrosine receptors or the neural cell adhesion molecule, to promote cell survival, neurite outgrowth, and synaptogenesis. The neuroprotective effect of exogenous GDNF has been shown in different experimental models of focal and global brain ischemia, by local administration of the trophic factor, using viral vectors carrying the GDNF gene and by transplantation of GDNF-expressing cells. These different strategies and the mechanisms contributing to neuroprotection by GDNF are discussed in this review. Importantly, neuroprotection by GDNF was observed even when administered after the ischemic injury. PMID- 22670841 TI - Ursodeoxycholic acid therapy in cystic fibrosis liver disease--a retrospective long-term follow-up case-control study. AB - BACKGROUND: The prevention and treatment of liver disease associated with cystic fibrosis remain a significant unresolved problem. AIM: To assess the long-term effects of continuous ursodeoxycholic acid (UDCA) therapy in cystic fibrosis patients with constantly elevated serum liver enzymes. METHODS: The primary endpoint was the incidence of overt liver disease. Between 1989 and 2005, UDCA treatment was started in 98 subjects from a cohort of 382 cystic fibrosis patients. These subjects were compared with a historic control group of 352 subjects who attended our centre between 1975 and 1989 before UDCA became standard treatment. For the long-term comparison of liver function and lung function tests, a group of 98 matched contemporary cystic fibrosis patients were compared with the 98 subjects treated with UDCA. RESULTS: Overt liver disease developed in only one of the 382 patients who was treated with UDCA for increased serum liver enzymes compared with nine patients in the historic control group (P < 0.05). Serum liver enzyme levels declined in most patients receiving UDCA treatment during the 17-year follow-up (87/98, P < 0.05). No difference was seen in lung function between subjects with cystic fibrosis-related liver disease and the matched controls. CONCLUSIONS: Regular and systematic screening for liver involvement enables early introduction of UDCA therapy in affected cystic fibrosis patients, reduces the development of severe liver disease and leads to a significant and persistent improvement in serum liver tests, without impairing long-term pulmonary outcome. PMID- 22670842 TI - Are the severe injuries of cutaneous leishmaniasis caused by an exacerbated Th1 response? AB - American tegumentary leishmaniasis (ATL) is a disease whose clinical features are strongly related to the type of immune response it induces. Herein we report an atypical presentation of cutaneous leishmaniasis in a woman with a severe and extensive sore located in her leg, and we describe the differences between the usual local immune response in ATL and the local immune response in this patient. We observed an intense inflammatory response characterized by Th1 cells and cytokines with conspicuous expression of Toll-like receptor 3 (TLR-3). Few parasites were present, but there was an extensive tissue damage. We also discuss the immunological factors that could be related to the atypical presentation. PMID- 22670843 TI - Capacitive energy storage in nanostructured carbon-electrolyte systems. AB - Securing our energy future is the most important problem that humanity faces in this century. Burning fossil fuels is not sustainable, and wide use of renewable energy sources will require a drastically increased ability to store electrical energy. In the move toward an electrical economy, chemical (batteries) and capacitive energy storage (electrochemical capacitors or supercapacitors) devices are expected to play an important role. This Account summarizes research in the field of electrochemical capacitors conducted over the past decade. Overall, the combination of the right electrode materials with a proper electrolyte can successfully increase both the energy stored by the device and its power, but no perfect active material exists and no electrolyte suits every material and every performance goal. However, today, many materials are available, including porous activated, carbide-derived, and templated carbons with high surface areas and porosities that range from subnanometer to just a few nanometers. If the pore size is matched with the electrolyte ion size, those materials can provide high energy density. Exohedral nanoparticles, such as carbon nanotubes and onion-like carbon, can provide high power due to fast ion sorption/desorption on their outer surfaces. Because of its higher charge-discharge rates compared with activated carbons, graphene has attracted increasing attention, but graphene had not yet shown a higher volumetric capacitance than porous carbons. Although aqueous electrolytes, such as sodium sulfate, are the safest and least expensive, they have a limited voltage window. Organic electrolytes, such as solutions of [N(C2H5)4]BF4 in acetonitrile or propylene carbonate, are the most common in commercial devices. Researchers are increasingly interested in nonflammable ionic liquids. These liquids have low vapor pressures, which allow them to be used safely over a temperature range from -50 degrees C to at least 100 degrees C and over a larger voltage window, which results in a higher energy density than other electrolytes. In situ characterization techniques, such as nuclear magnetic resonance (NMR), small-angle X-ray scattering (SAXS) and small-angle neutron scattering (SANS), and electrochemical quartz crystal microbalance (EQCM) have improved our understanding of the electrical double layer in confinement and desolvation of ions in narrow pores. Atomisitic and continuum modeling have verified and guided these experimental studies. The further development of materials and better understanding of charged solid-electrolyte interfaces should lead to wider use of capacitive energy storage at scales ranging from microelectronics to transportation and the electrical grid. Even with the many exciting results obtained using newer materials, such as graphene and nanotubes, the promising properties reported for new electrode materials do not directly extrapolate to improved device performance. Although thin films of nanoparticles may show a very high gravimetric power density and discharge rate, those characteristics will not scale up linearly with the thickness of the electrode. PMID- 22670844 TI - Invasive behavior of small diameter melanomas. PMID- 22670845 TI - Mutation spectra of S-(2-hydroxy-3,4-epoxybutyl)glutathione: comparison with 1,3 butadiene and its metabolites in the Escherichia coli rpoB gene. AB - S-(2-Hydroxy-3,4-epoxybutyl)glutathione (DEB-GSH conjugate) is formed from the reaction of 1,2:3,4-diepoxybutane (DEB) with glutathione (GSH), and the conjugate is considerably more mutagenic than several other butadiene-derived epoxides including DEB-in Salmonella typhimurium TA1535 [Cho, S.-H., (2010) Chem. Res. Toxicol. 23, 1544-1546]. We previously identified six DNA adducts in the reaction of the DEB-GSH conjugate with nucleosides and calf thymus DNA and two DNA adducts in livers of mice and rats treated with DEB [Cho, S.-H. and Guengerich, F. P. (2012) Chem. Res. Toxicol. 25, 706-712]. To define the role of GSH conjugation in 1,3-butadiene (BD) metabolism and characterize the mechanism of GSH transferase (GST)-enhanced mutagenicity of DEB, mutation spectra of BD and its metabolites in the absence and presence of GST/GSH and mouse liver microsomes were compared in the rpoB gene of Escherichia coli TRG8. The presence of GST considerably enhanced mutations. The mutation spectra derived from the DEB-GSH conjugate, the DEB/GST/GSH system, and the BD/mouse liver microsomes/GST/GSH system matched each other and were different from those derived from the other systems devoid of GSH. The major adducts in E. coli TRG8 cells treated with the DEB/GST/GSH system, the BD/mouse liver microsomes/GST/GSH system, or the DEB-GSH conjugate were S-[4 (N(7)-guanyl)-2,3-dihydroxybutyl]GSH, S-[4-(N(3)-adenyl)-2,3-dihydroxybutyl]GSH, and S-[4-(N(6)-deoxyadenosinyl)-2,3-dihydroxybutyl]GSH, indicating the presence of the GSH-containing DNA adducts in the systems. These results, along with the strong enhancement of mutagenicity by GST in this system, indicate the relevance of these GSH-containing DNA adducts. PMID- 22670846 TI - Comparison of Macintosh and AirtraqTM laryngoscopes in obese patients placed in the ramped position. AB - This study compared intubation conditions produced by the Macintosh and AirtraqTM laryngoscopes when used in obese patients in the ramped position. One hundred and thirty-two patients having bariatric surgery were placed in the ramped position and randomly assigned to have their tracheas intubated using either the Macintosh (n=64) or an Airtraq (n=68) laryngoscope. Mean (SD) intubation times were 37 (23) s and 14 (3) s for Macintosh and Airtraq, respectively (p<0.0001). Compared with the Macintosh laryngoscope, the Airtraq laryngoscope provided an improved vocal cord view as assessed by the Cormack and Lehane score (number of patients with Cormack-Lehane scores of 1/2/3/4/37/20/4/3 for the Macintosh, and 65/3/0/0 for the Airtraq laryngoscopes, p<0.0001). One patient in the Macintosh group had a failed intubation and intubation was achieved with the Airtraq. For obese patients in ramped position, Airtraq affords faster tracheal intubation than the Macintosh laryngoscope. PMID- 22670847 TI - The urban-rural disparity in nursing home quality indicators: the case of facility-acquired contractures. AB - OBJECTIVE: To identify and quantify the sources of the urban-rural disparity in facility-acquired contracture rates in nursing homes. DATA SOURCES: Survey inspection data of U.S. nursing homes from 1999 to 2008 and standardized national rural definition file from the Rural-Urban Commuting Area Codes. STUDY DESIGN: We estimated regressions of facility-level contracture rate as a function of urban rural categories (urban, micropolitan, small rural town, and isolated small rural town) and other related facility characteristics to identify size of the urban rural disparity. We used Blinder-Oaxaca decomposition techniques to determine the extent to which the disparity is attributable to the differences in facility and aggregate resident characteristics. PRINCIPAL FINDINGS: Rural nursing homes have higher contracture rates than urban nursing homes. About half of the urban-rural disparity is explained by differences in observable characteristics among urban and rural nursing homes. Differences in staffing levels explain less than 5 percent of the disparity, case-mix explains 6-8 percent, and structure and operational characteristics account for 10-22 percent of the disparity. CONCLUSION: While a lower level and quality of staffing are a concern for rural nursing homes, facility structure and funding sources explain a larger proportion of the urban-rural disparity in the quality of care. PMID- 22670849 TI - Influence of polarization setting on gold nanorod signal at nonplasmonic wavelengths under differential interference contrast microscopy. AB - Researchers rely on a variety of microscopic techniques for observing and tracking anisotropic nanoparticles in real time experiments. This technical note focuses on the optical behavior exhibited by gold nanorods at nonplasmonic wavelengths under differential interference contrast microscopy (DIC). Intense diffraction patterns appear at nonplasmonic wavelengths, and the behavior of these patterns can be altered by adjusting the surrounding medium or the polarizer setting. Such patterns are absent when linear and crossed polarizations are utilized. Making polarization adjustments is important in DIC microscopy, because it affects bias retardation and image contrast. The nonplasmonic diffraction bands that were observed could potentially be exploited for rotational tracking, but more importantly, researchers should exhibit care in selecting a nanorod sample and the polarization setting when working with DIC microscopy. PMID- 22670848 TI - Malaria parasite type 4 equilibrative nucleoside transporters (ENT4) are purine transporters with distinct substrate specificity. AB - Malaria, caused by Plasmodia parasites, affects hundreds of millions of people. As purine auxotrophs, Plasmodia use transporters to import host purines for subsequent metabolism by the purine salvage pathway. Thus purine transporters are attractive drug targets. All sequenced Plasmodia genomes encode four ENTs (equilibrative nucleoside transporters). During the pathogenic intraerythrocytic stages, ENT1 is a major route of purine nucleoside/nucleobase transport. Another plasma membrane purine transporter exists because Plasmodium falciparum ENT1 knockout parasites survive at supraphysiological purine concentrations. The other three ENTs have not been characterized functionally. Codon-optimized Pf- (P. falciparum) and Pv- (Plasmodium vivax) ENT4 were expressed in Xenopus laevis oocytes and substrate transport was determined with radiolabelled substrates. ENT4 transported adenine and 2'-deoxyadenosine at the highest rate, with millimolar-range apparent affinity. ENT4-expressing oocytes did not accumulate hypoxanthine, a key purine salvage pathway substrate, or AMP. Micromolar concentrations of the plant hormone cytokinin compounds inhibited both PfENT4 and PvENT4. In contrast with PfENT1, ENT4 interacted with the immucillin compounds in the millimolar range and was inhibited by 10 MUM dipyridamole. Thus ENT4 is a purine transporter with unique substrate and inhibitor specificity. Its role in parasite physiology remains uncertain, but is likely to be significant because of the strong conservation of ENT4 homologues in Plasmodia genomes. PMID- 22670850 TI - Precepting and symbolic interactionism--a theoretical look at preceptorship during clinical practice. AB - AIM: To present a discussion of precepting through the use of symbolic interactionism as exemplified by findings from an ethnographic study. BACKGROUND: It is a well-known fact that clinical practice, where students are supervised by precepting nurses, is an important part of nursing education. Several previous studies have stressed the vital role preceptors have for the development of student nurses' clinical competence. Despite this, few of these findings are discussed from a theoretical standpoint to further explain and illustrate the complexity of preceptorship. DATA SOURCES: This article builds on findings from an ethnographic study undertaken between November 2006-May 2007 and again between March-September 2009. Full details of the empirical findings have been reported elsewhere. DISCUSSION: Precepting can be understood as a trusting relationship between preceptor and student interacting and sharing nursing activities. The participants' actions will influence and shape the meaning and understanding of these activities. IMPLICATIONS FOR NURSING: Precepting is a complex and advanced role for nurses that they need to be properly prepared for. Thus, preceptor preparation needs to be organized in collaboration between healthcare organizations and universities. It is suggested that preceptor preparation programmes should focus on reflection, critical thinking and communication skills. CONCLUSION: Symbolic interactionism can serve as a potential theory that will expand the understanding of and give new perspectives of nursing practice. It would therefore be encouraging to see further testing of suitable theories to interpret empirical findings and create opportunities for practice improvement. PMID- 22670851 TI - Digital in-line holography on amplitude and phase objects prepared with electron beam lithography. AB - We report on the fabrication and characterization of amplitude and phase samples consisting of well defined Au or Al features formed on ultrathin silicon nitride membranes. The samples were manufactured using electron beam lithography, metallization and a lift-off technique, which allow precise lateral control and thickness of the metal features. The fabricated specimens were evaluated by conventional microscopy, atomic force microscopy and with the digital in-line holography set-up at the Lund Laser Centre. The latter uses high-order harmonic generation as a light source, and is capable of recovering both the shape and phase shifting properties of the samples. We report on the details of the sample production and on the imaging tests with the holography set-up. PMID- 22670852 TI - Sex differences in cognition in healthy elderly individuals. AB - Sex differences in patterns of cognitive test performance have been attributed to factors, such as sex hormones or sexual dimorphisms in brain structure, that change with normal aging. The current study examined sex differences in patterns of cognitive test performance in healthy elderly individuals. Cognitive test scores of 957 men and women (age 67-89), matched for overall level of cognitive test performance, age, education, and depression scale score, were compared. Men and women were indistinguishable on tests of auditory divided attention, category fluency, and executive functioning. In contrast, women performed better than men on tests of psychomotor speed and verbal learning and memory, whereas men outperformed women on tests of visuoconstruction and visual perception. Our finding that the pattern of sex differences in cognition observed in young adults is observed in old age has implications for future studies of both healthy elderly individuals and of those with cognitive disorders. PMID- 22670853 TI - Ketoconazole ion-exchange fiber complex: a novel method to reduce the individual difference of bioavailability in oral administration caused by gastric anacidity. AB - Water insoluble faintly alkaline drugs often have potential absorption problem in gastrointestinal tract in oral administration for patients with gastric anacidity. The purpose of the present study is to develop a novel method to improve the absorption of the water insoluble faintly alkaline drug in peroral administration. This method is based on ion exchange of ion-exchange fibers. Water-insoluble faintly alkaline drug ketoconazole was used as a model drug. Ketoconazole and the active groups of the ion-exchange fibers combined into ion pairs based on the acid-base reaction. This drug carrier did not release drugs in deionized water, but in water solution containing other ions it would release the drugs into the solution by ion exchange. Confirmed by the X-ray diffraction and the differential scanning calorimetry (DSC), the ketoconazole combined onto the ion-exchange fibers was in a highly molecular level dispersed state. The improved dissolution of ketoconazole ion-exchange fiber complexes is likely to originate from this ketoconazole's highly dispersed state. Furthermore, due to this ketoconazole's highly dispersed state, ketoconazole ion-exchange fiber complexes significantly decreased the individual difference of absorption in oral administration of ketoconazole caused by the fluctuation of the acid degree in the gastric fluid. PMID- 22670854 TI - The impact of anxiety on social decision-making: behavioral and electrodermal findings. AB - Anxiety plays an important role in social behavior. For instance, high-anxious individuals are more likely to avoid such social interactions as communicating with strangers. In this study, we investigate the impact of anxiety on social decision-making. The classic ultimatum game (UG) paradigm was utilized in concert with skin conductance recording. Behavioral results reveal that when playing as responders, high-trait anxiety (HTA) participants with lower levels of self esteem, as well as low-trait anxiety (LTA) participants with higher levels of impulsivity, were more likely to accept human-proposed inequitable offers. In addition, the HTA participants rejected more computer-proposed inequitable offers than did LTA participants. Moreover, the skin conductance response to inequitable offers was correlated with levels of anxiety in the HTA group, but not in the LTA group. In conclusion, people differing in levels of anxiety showed distinct behavior patterns and autonomic neural responses during social decision-making, whereas the levels of self-esteem, impulsivity, and depression might be additional moderating factors. These findings contextualize high-anxious people's avoidance tendency in social interaction. PMID- 22670855 TI - Differences in development and the prevalence of obesity among children and adolescents in different socioeconomic status districts in Shandong, China. AB - BACKGROUND: There are wide-ranging differences in human growth, not only between ethnic groups but also between regions. Shandong is one of the most populous provinces in China, with inequalities of regional economic status. However, no studies on the differences in development among children and adolescents in different districts have been reported. AIM: This study assessed the differences in height, weight and prevalence of obesity among children and adolescents of different socioeconomic status (SES) districts in Shandong, China. SUBJECTS AND METHODS: Data for this study were obtained from a large cross-sectional survey of schoolchildren. A total of 42 286 students (21 222 boys and 21 064 girls) aged 7 18 years from 16 districts participated in this study. Height and weight of all subjects were measured and BMI was calculated from their height and weight. Prevalence rates of obesity and overweight were determined by comparing calculated BMIs (kg/m(2)) to International Obesity Task Force (IOTF) cut-offs. Each of the 16 districts was assigned an SES ranking (low, moderate, high) based on per capita GDP and income in urban and rural areas. Comparisons of height, weight and the prevalence of overweight and obesity among different groups were made. RESULTS: Significant differences between SES groups were observed for height, weight and the prevalence of overweight and obesity. Boys and girls from high SES group were taller, heavier and more likely to be obese than their peers from moderate and low SES groups. The prevalences of combined overweight and obesity in the three SES groups were 18.46%, 21.08% and 27.31% in boys and 10.43%, 12.42% and 15.18% in girls, respectively. CONCLUSION: There have been obvious regional variations in development and the prevalence of obesity in children and adolescents in Shandong, China, These variations in development and prevalence of obesity in children and adolescents among different SES districts being related to the local SES, process of urbanization, living environments, nutritional status, dietary pattern, physical activity and public health. PMID- 22670857 TI - Carbene-stabilized beryllium borohydride. AB - The reaction of N-heterocyclic carbene, L:, with BeCl(2) quantitatively yields L:BeCl(2)1 (L: = :C{N(2,6-Pr(i)(2)C(6)H(3))CH}(2)). The carbene-stabilized beryllium borohydride monomer L:Be(BH(4))(2)2 is prepared by the reaction of 1 with LiBH(4). Compound 3, prepared by the reaction of 2 with Na(2)[Fe(CO)(4)].dioxane, represents an unusual "dual reduction" of the imidazole ring (i.e., hydroboration of the C?C backbone and hydrogenation of the C2 carbene center). PMID- 22670856 TI - Randomized double-blind clinical trial of autologous serum versus artificial tears in dry eye syndrome. AB - PURPOSE: To determine symptoms improvement in dry eye patients with short-term autologous serum (AS) eyedrops treatment using the standardized Ocular Surface Disease Index (OSDI) survey. MATERIALS AND METHODS: A double-blind randomized crossover clinical trial was conducted, comparing short-term (2 weeks) topical treatment with AS eyedrops diluted at 20% versus conventional artificial tears treatment in adult severe dry eye syndrome (DES) patients. The main outcome measure was assessment of symptoms with OSDI survey. Secondary outcomes were corneal and conjunctival fluorescein staining score of OXFORD and tear break up time (TBUT). The protocol was registered in www.clinicaltrials.gov , ID number: NCT00779987. RESULTS: Twelve severe DES patients were included. Autologous serum treatment showed a statistically significant (p = 0.002) higher OSDI decrease (50%) versus conventional treatment (22%). There were no significant changes in objectives parameters (OXFORD and TBUT). CONCLUSIONS: Severe DES patients treated with AS achieve better symptoms improvement compared to artificial tears in a short-term treatment. PMID- 22670858 TI - Detection of dengue virus in sera of Brazilian blood donors. AB - BACKGROUND: Dengue is the most important arboviral disease in the world. Dengue viruses (DENVs) have produced huge outbreaks in Brazil in the past 25 years with more than 5 million reported cases. During these epidemics, asymptomatic individuals infected with DENV could donate blood and serve as a source of virus dissemination in the community. Here, we studied the circulation of DENV in healthy individuals during an epidemic outbreak. STUDY DESIGN AND METHODS: The study included 500 serum samples from healthy blood donors collected at the Hemotherapy Center of Ribeirao Preto, Brazil, during a dengue outbreak. The presence of DENV RNA in the serum samples was screened by real-time reverse transcription-polymerase chain reaction (PCR). The virus serotype was determined by a heminested PCR procedure. A partial fragment of the NS5 gene sequence was used for phylogenetic analysis. RESULTS: DENV RNA was detected in the serum sample of 2 of 500 (0.4%) individuals. Both of them were infected with DENV-3 Genotype III, a virus that has been circulating in Brazil in the past decade. CONCLUSION: Individuals with asymptomatic DENV infection can be blood donors and serve as a source of virus dissemination in the community. Further studies are needed to determine the risk of recipient infection by DENV as a result of transfusion in Brazil, especially during epidemic periods. PMID- 22670859 TI - Crystallization and vitrification of a cyanurate trimer in nanopores. AB - The effects of nanopore confinement on the crystallization and vitrification of a low molecular weight organic material, tris(4-cumylphenol)-1,3,5-triazine, are investigated using differential scanning calorimetry. The material shows cold crystallization and subsequent melting in the bulk state. Under the nanoconfinement of controlled pore glasses (CPG), cold crystallization and melting shift to lower temperatures. Crystallization kinetics are hindered in nanoconfinement, and no crystallization occurs in 13 nm diameter pores over the course of a week. Using a traditional Avrami analysis, the restricted crystallization under nanopore confinement is quantified; for crystallization at 80 degrees C, the Avrami exponent decreases with decreasing pore size and the overall crystallization rate is approximately 30 times slower for material confined in 50 nm diameter pores than the bulk. When compared at the temperature at which the crystallization rate is a maximum, the Avrami exponent is higher in nanoconfined samples and the crystallization rate is approximately 10 times slower for material confined in 50 nm diameter pores. Under CPG nanoconfinement, the glass transition temperature also decreases and shows two values; interestingly, the T(g) values further decrease with increasing crystallinity. PMID- 22670860 TI - Pharmacokinetic interaction study between quercetin and valsartan in rats and in vitro models. AB - Valsartan is a potent, orally active non-peptide tetrazole derivative and selectively inhibits angiotensin II receptor type 1 which causes reduction in blood pressure and is used in treatment of hypertension. The risk of heart disease mortality decreased significantly as flavonoid intake increased. Interestingly, the flavonoid-containing foods contain a high amount of Quercetin. The objective of this study was to evaluate the influence of quercetin on the pharmacokinetics of valsartan. In vivo studies were performed on rats. Rats were treated with quercetin (10 mg/kg) and valsartan (10 mg/kg), blood samples were collected at 1, 1.5, 2, 2.5, 3, 3.5, 4, 6 and 8 h. Plasma concentration of valsartan was estimated by Reverse Phase (RP-HPLC). Quercetin significantly increases the plasma concentration of valsartan and peak concentration (70.45 ug/mL) was achieved at 3.5 h. In vitro studies were performed on rat intestinal everted sacs. The transport of valsartan from serosal side to mucosal side decreased from 53.12 +/- 1.27 to 40.15 +/- 0.45 ug/mL in the presence of quercetin and from 53.12 +/- 1.27 to 28.68 +/- 0.31 ug/mL in the presence of verapamil (standard P-glycoprotein (P-gp) inhibitor) at 120 min. Verapamil is a potent P-gp and CYP3A4 inhibitor. Quercetin is a P-gp inhibitor and may be an inhibitor of CYP3A4. The simultaneous administration of quercetin significantly increases the intestinal absorption and decreases the efflux of valsartan. The observed effect may be beneficial to develop oral valsartan dosage forms using safe P-gp inhibitor (quercetin) to improve its oral bioavailability. PMID- 22670861 TI - Passive smoking exposure might be associated with hypermetropia. AB - PURPOSE: The aim of the study was to explore the relationship between nicotine exposure in children via passive smoking and the refractive errors of these children. METHODS: The study included 300 children between the age of 5 and 12 years. Children were subjected to detailed history taking with special emphasis on the degree of exposure to passive smoke. They underwent a complete ophthalmological evaluation including cycloplegic refraction. Urine samples were collected to measure urinary levels of cotinine and creatinine with subsequent calculation of the cotinine creatinine ratio (CCR). RESULTS: The refractive error assessment indicated 122 hypermetropic (40.7%), 86 myopic (28.7%) and 92 emmetropic (30.7%) children. Gender and age were not statistically different between the three groups. Urinary cotinine was significantly higher in the hypermetropic than myopic and emmetropic groups (p < 0.0001). Moreover, it was significantly higher in the emmetropic group than the myopic one (p = 0.02). Cotinine/creatinine ratio (CCR) and the parental number of cigarettes smoked per day showed the same pattern as urinary cotinine. Considering all 300 data, the spherical equivalent refractive error was significantly correlated with the number of cigarettes smoked by the parents, CCR and urinary cotinine levels cotinine (p < 0.0001 for all correlations). CONCLUSION: Passive smoking indices were related to the degree of refractive error and children with hypermetropia showed significantly higher passive smoking indices. We suggest that passive smoking might be associated with a refractive error shift towards hypermetropia. PMID- 22670862 TI - Investigation of mutations in the synaptonemal complex protein 3 (SYCP3) gene among azoospermic infertile male patients in the Turkish population. AB - To investigate possible mutations and/or single nucleotide polymorphisms in the synaptonemal complex protein 3 (SYCP3) gene among nonobstructive azoospermic infertile males in a Turkish population, 75 nonobstructive azoospermic infertile male patients were included in the study. These patients were unrelated to each other and had 46,XY chromosome structure without Y microdeletion. In addition, 75 individuals whose fertility was proven by reproduction were enrolled in the study as controls. Nine exon deep intronic primers belonging to the SYCP3 gene were designed and amplified by PCR, and the nucleotide sequences were identified by DNA sequence analysis. DNA sequence analysis was used to detect mutations and/or single nucleotide polymorphisms in the SYCP3 gene. No mutations were detected in the 9 exons of SYCP3. A total of eleven variations, however, were detected: seven have been identified in the NCBI SNP database, whereas four have not. On the basis of the results, we agree with the idea that SYCP3 mutations are not associated with the genetic susceptibility for meiotic arrest in infertile male patients with nonobstructive azoospermia in the Turkish population and that further studies investigating the other components of the synaptonemal complex protein (SYCP1, SYCP2) should be conducted. PMID- 22670863 TI - Human platelet lysate gel provides a novel three dimensional-matrix for enhanced culture expansion of mesenchymal stromal cells. AB - Cell culture in regenerative medicine needs to facilitate efficient expansion according to good manufacturing practice requirements. Human platelet lysate (HPL) can be used as a substitute for fetal calf serum without the risk of xenogeneic immune reactions or transmission of bovine pathogens. Heparin needs to be added as anticoagulant before addition of HPL to culture medium; otherwise, HPL-medium forms a gel within 1 h. Here, we demonstrated that such HPL-gels provide a suitable 3D-matrix for cell culture that-apart from heparin-consists of the same components as the over-layered culture medium. Mesenchymal stromal cells (MSCs) grew in several layers at the interface between HPL-gel and HPL-medium without contact with any artificial biomaterials. Notably, proliferation of MSCs was much higher on HPL-gel compared with tissue culture plastic. Further, the frequency of initial fibroblastoid colony forming units (CFU-f) increased on HPL gel. The viscous consistency of HPL-gel enabled passaging with a convenient harvesting and reseeding procedure by pipetting cells together with their HPL matrix-this method does not require washing steps and can easily be automated. The immunophenotype and in vitro differentiation potential toward adipogenic, osteogenic, and chondrogenic lineage were not affected by culture-isolation on HPL-gel. Taken together, HPL-gel has many advantages over conventional plastic surfaces: it facilitates enhanced CFU-f outgrowth, increased proliferation rates, higher cell densities, and nonenzymatic passaging procedures for culture expansion of MSCs. PMID- 22670864 TI - Ruthenium terpyridine complexes containing a pyrrole-tagged 2,2'-dipyridylamine ligand-synthesis, crystal structure, and electrochemistry. AB - Ruthenium(II) terpyridine complexes containing the pyrrole-tagged 2,2' dipyridylamine ligand PPP (where PPP stands for N-(3-bis(2 pyridyl)aminopropyl)pyrrole with the general formula [Ru(tpy)(PPP)X](n+) (1, X = Cl(-); 2, X = H(2)O; 3, X = CH(3)CN; tpy = 2,2':6',2"-terpyridine) have been synthesized and characterized by (1)H NMR, IR, UV-vis, mass spectrometry, and elemental analysis. 1 and 2 have been structurally characterized by X-ray crystallography. Both 1 and 2 were successfully immobilized onto glassy carbon electrode via anodic oxidation of the pyrrole moiety on the PPP ligand to give stable and highly electroactive polymer films. Cyclic voltammetric studies of 1 in acetonitrile revealed a Ru(III)/Ru(II) couple at 0.4 V vs Cp(2)Fe(+/0) initially, but another redox couple resulting from chloride substitution by acetonitrile developed at E(1/2) = 0.82 V upon repetitive potential scan. This ligand substitution was induced by the acidic local environment caused by the release of protons during pyrrole polymerization. The electropolymerization of 2 in aqueous medium allowed the observation of the formation of Ru(IV)?O species in polypyrrole film. As the film grew thicker, the size of the Ru(III)/(/)Ru(II) couple (E(1/2) = 0.8 V vs SCE at pH 1) of poly[Ru(tpy)(PPP)(OH(2))](n+) increased accordingly, whereas the growth of the Ru(IV)/Ru(III) couple (E(1/2) = 0.89 V vs SCE at pH 1) leveled off after the film had reached a certain thickness. The Pourbaix diagram of the E(1/2) of the Ru(III) /Ru(II) and Ru(IV)/Ru(III) couples vs pH of the electrolyte medium has been obtained. The resulting poly[Ru(tpy)(PPP)(OH(2))](n+) film is electrocatalytically active toward the oxidation of benzyl alcohol. PMID- 22670865 TI - Harm reduction and the medicalisation of tobacco use. AB - In tobacco control the focus has, for some time, been on abstinence from all types of tobacco use as the only solution to the problem of smoking, and harm reduction approaches are controversial. The most recent English tobacco strategy has incorporated harm reduction approaches in the form of new 'routes' to quitting smoking that encourage those who cannot quit to use safer sources of nicotine. This move away from a focus on abstinence can be seen as the result of gradual shifts over the past 50 years in the way that that the problem of smoking is understood and the solutions that are offered. These shifts have involved increasingly seeing tobacco use as a medical problem. This article uses conceptual tools from science and technology studies to examine developments over the last decade in England, primarily the increasing importance of harm reduction approaches. Drawing on 20 semi-structured qualitative interviews with key stakeholders and documentary analysis, I suggest that the shape harm reduction has taken in English tobacco control policy has been another shift towards the medicalisation of tobacco use, but that this process has occurred in ways that provide a contrast to commonly outlined 'drivers' of medicalisation. PMID- 22670867 TI - Piebaldism. AB - Piebaldism is an uncommon autosomal dominantly inherited pigment anomaly characterized by a congenital white forelock and leukoderma on the frontal scalp, forehead, ventral trunk and extremities. It is caused by a loss-of-function mutation in the KIT gene. Genetic analyses reveal a consistent genotype-phenotype relationship in piebaldism. However, recently reported cases of piebaldism that are milder or severer than genetically expected indicate that other factors, such as a modifier gene of MC1R, influence skin and hair color. The KIT ligand/KIT that triggers the Ras/mitogen-activated protein kinase signaling pathway play essential functions in the migration, proliferation, survival, melanogenesis and melanosome transfer of the melanocytes. We summarize current research progress in piebaldism and related disorders. PMID- 22670868 TI - The health care jobs fallacy. PMID- 22670869 TI - Gold nanoparticle-embedded porous graphene thin films fabricated via layer-by layer self-assembly and subsequent thermal annealing for electrochemical sensing. AB - A uniform three-dimensional (3D) gold nanoparticle (AuNP)-embedded porous graphene (AuEPG) thin film has been fabricated by electrostatic layer-by-layer assembly of AuNPs and graphene nanosheets functionalized with bovine serum albumin and subsequent thermal annealing in air at 340 degrees C for 2 h. Scanning electron microscopy (SEM) investigations for the AuEPG film indicate that an AuNP was embedded in every pore of the porous graphene film, something that was difficult to achieve with previously reported methods. The mechanism of formation of the AuEPG film was initially explored. Application of the AuEPG film in electrochemical sensing was further demonstrated by use of H(2)O(2) as a model analyte. The AuEPG film-modified electrode showed improved electrochemical performance in H(2)O(2) detection compared with nonporous graphene-AuNP composite film-modified electrodes, which is mainly attributed to the porous structure of the AuEPG film. This work opens up a new and facile way for direct preparation of metal or metal oxide nanoparticle-embedded porous graphene composite films, which will enable exciting opportunities in highly sensitive electrochemical sensors and other advanced applications based on graphene-metal composites. PMID- 22670870 TI - Infrared matrix-assisted laser desorption/ionization orthogonal-time-of-flight mass spectrometry employing a cooling stage and water ice as a matrix. AB - Although water ice has been utilized in the past as a matrix for infrared matrix assisted laser desorption/ionization mass spectrometry (IR-MALDI-MS), it has not found a wider use due to limitations in the analytical performance and technical demands on the employment of the necessary cooling stage. Here, we developed a temperature-controlled sample stage for use with an orthogonal time-of-flight mass spectrometer (MALDI-o-TOF-MS). The stage utilizes a combination of liquid nitrogen cooling and counterheating with a Peltier element. It allows adjustment of the sample temperature between ~-120 degrees C and room temperature. To identify optimal irradiation conditions for IR-MALDI with the water ice matrix, we first investigated the influence of excitation wavelength, varied between 2.7 and 3.1 MUm, and laser fluence on the signal intensities of molecular substance P ions. These data suggest the involvement of transient melting of the ice during the laser pulse and primary energy deposition into liquid water. As a consequence, the best analytical performance is obtained at a wavelength corresponding to the absorption maximum of liquid water of about 2.94 MUm. The current data significantly surpass the previously reported analytical features. The particular softness of the method is, for example, exemplified by the analysis of noncovalently bound holo-myoglobin and of ribonuclease B. This is also the first report demonstrating the analysis of an IgG monoclonal antibody (MW ~ 150 kDa) from a water ice matrix. Untypical for MALDI-MS, high charge states of multiply protonated species were moreover observed for some of the investigated peptides and even for lacto-N-fucopentaose II oligosaccharides. Using water ice as matrix is of particular interest for MALDI MS profiling and imaging applications since matrix-free spectra are produced. The MS and tandem MS analysis of metabolites directly from frozen food samples is demonstrated with the example of a strawberry fruit. PMID- 22670871 TI - Late diagnosis of ectodermal dysplasia syndrome. AB - This case study reports the clinical, skin biopsy and molecular findings in a 56 year-old Filipino man with the autosomal recessive ectodermal dysplasia disorder, Schopf-Schulz-Passarge syndrome, the precise nature of which was established only after reading of a similar case in this journal. In addition to the late diagnosis, successful clinical management of his acral hyperkeratosis and ulceration has been difficult, with oral retinoids exacerbating the skin fragility. PMID- 22670872 TI - MMP proteolysis of the human extracellular matrix protein aggrecan is mainly a process of normal turnover. AB - Although it has been shown that aggrecanases are involved in aggrecan degradation, the role of MMP (matrix metalloproteinase) aggrecanolysis is less well studied. To investigate MMP proteolysis of human aggrecan, in the present study we used neoepitope antibodies against MMP cleavage sites and Western blot analysis to identify MMP-generated fragments in normal and OA (osteoarthritis/osteoarthritic) cartilage, and in normal, knee injury and OA and SF (synovial fluid) samples. MMP-3 in vitro digestion showed that aggrecan contains six MMP cleavage sites, in the IGD (interglobular domain), the KS (keratan sulfate) region, the border between the KS region and CS (chondroitin sulfate) region 1, the CS1 region, and the border between the CS2 and the G3 domain, and kinetic studies showed a specific order of digestion where the cleavage between CS2 and the G3 domain was the most preferred. In vivo studies showed that OA cartilage contained (per dry weight) 3.4-fold more MMP-generated FFGV fragments compared with normal cartilage, and although aggrecanase-generated SF-ARGS concentrations were increased 14-fold in OA and knee-injured patients compared with levels in knee-healthy reference subjects, the SF-FFGV concentrations did not notably change. The results of the present study suggest that MMPs are mainly involved in normal aggrecan turnover and might have a less active role in aggrecan degradation during knee injury and OA. PMID- 22670873 TI - Copper-catalyzed complete regio- and stereoselective cyclization of 1-aryl-3 sulfanyl-4-oxahepta-1,6-diynes triggered by alkynylation. AB - Copper(I)-catalyzed alkynylation-cyclization of 4-oxahepta-1,6-diynes 1 with a wide variety of terminal alkynes proceeded to give (3E,4Z)-3 (phenylsulfanylmethylene)-4-(2-propynylidene)tetrahydrofuran-2-yl]benzenes 2aa-he in high yields with complete regio- and stereoselectivity. PMID- 22670874 TI - The cost of an additional disability-free life year for older Americans: 1992 2005. AB - OBJECTIVE: To estimate the cost of an additional disability-free life year for older Americans in 1992-2005. DATA SOURCE: This study used 1992-2005 Medicare Current Beneficiary Survey, a longitudinal survey of Medicare beneficiaries with a rotating panel design. STUDY DESIGN: This analysis used multistate life table model to estimate probabilities of transition among a discrete set of health states (nondisabled, disabled, and dead) for two panels of older Americans in 1992 and 2002. Health spending incurred between annual health interviews was estimated by a generalized linear mixed model. Health status, including death, was simulated for each member of the panel using these transition probabilities; the associated health spending was cross-walked to the simulated health changes. PRINCIPAL FINDINGS: Disability-free life expectancy (DFLE) increased significantly more than life expectancy during the study period. Assuming that 50 percent of the gains in DFLE between 1992 and 2005 were attributable to increases in spending, the average discounted cost per additional disability-free life year was $71,000. There were small differences between gender and racial/ethnic groups. CONCLUSIONS: The cost of an additional disability-free life year was substantially below previous estimates based on mortality trends alone. PMID- 22670875 TI - Decorin as a new treatment alternative in Peyronie's disease: preliminary results in the rat model. AB - The purpose of this study is to investigate the effect of decorin, a naturally occurring proteoglycan with anti-transforming growth factor beta (TGF-beta) activity, on the rat model of Peyronie's disease (PD). Twenty-five adult male Sprague-Dawley rats were divided in three groups: I) TGF-beta (0.5 MUg) injected (n: 8); II) TGF-beta injected and decorin treated (n: 8); and III) controls (n: 9). Decorin (0.5 MUg per day) was given with intracavernous injection on the second, third, fourth and fifth day following TGF-beta injection. All rats underwent electrical stimulation of the cavernous nerve after 6 weeks. Intracavernosal and arterial blood pressures were measured during this procedure. Cross-sections of the rat penises were examined using Mason trichrome and H&E stains. Statistical analyses were carried out using one-way anova. Histopathological examinations confirmed the Peyronie's-like condition in TGF beta-injected rats, which exhibited a thickening of the tunica albuginea (TA), when compared to controls. Disorganisation of collagen on the TA was also prominent in TGF-beta-injected rats, but not in decorin-treated and control rats. Decorin-treated rats showed significantly higher maximal intracavernosal pressure (MIP) responses to cavernous nerve stimulation, when compared to group 1 (P < 0.05). Our results indicate that decorin antagonises the effects of TGF-beta in the rat model of PD and prevents diminished erectile response to cavernous nerve stimulation. PMID- 22670876 TI - Culture in social neuroscience: a review. AB - The aim of this review is to highlight an emerging field: the neuroscience of culture. This new field links cross-cultural psychology with cognitive neuroscience across fundamental domains of cognitive and social psychology. We present a summary of studies on emotion, perspective-taking, memory, object perception, attention, language, and the self, showing cultural differences in behavior as well as in neural activation. Although it is still nascent, the broad impact of merging the study of culture with cognitive neuroscience holds mutual distributed benefits for multiple related fields. Thus, cultural neuroscience may be uniquely poised to provide insights and breakthroughs for longstanding questions and problems in the study of behavior and thought, and its capacity for integration across multiple levels of analysis is especially high. These findings attest to the plasticity of the brain and its adaptation to cultural contexts. PMID- 22670877 TI - Combined fulminant frontotemporal dementia and amyotrophic lateral sclerosis associated with an I113T SOD1 mutation. AB - Mutations in the gene for superoxide dismutase type 1 cause amyotrophic lateral sclerosis (ALS), but are not thought to be associated with frontotemporal dementia (FTD). A lack of detailed case reports is one reason, among others, for this skepticism. This case report comments on a patient with familial ALS caused by I113T mutation in the SOD1 gene presenting with progressive cognitive and behavioral decline two years before developing progressive motor degeneration. In conclusion, this case provides evidence that SOD1 mutations can be associated with FTD. PMID- 22670878 TI - REM behavior disorder associated with familial amyotrophic lateral sclerosis. AB - The association between RBD and synucleinopathies is well known. However, the association between RBD and other neuromuscular diseases has not been as well described. Our case study describes two siblings with familial ALS, confirmed by the identification of the L84F mutation in the SOD1 gene, and RDB. We hope this case study will promote future studies on the prevalence of this association and will stimulate research in identifying the underlying pathogenic mechanism. PMID- 22670879 TI - Amyotrophic lateral sclerosis and riluzole use during pregnancy: a case report. PMID- 22670880 TI - Prognostic categories for amyotrophic lateral sclerosis. AB - Our objective was to generate a prognostic classification method for amyotrophic lateral sclerosis (ALS) from a prognostic model built using clinical variables from a population register. We carried out a retrospective multivariate analysis of 713 patients with ALS over a 20-year period from the South-East England Amyotrophic Lateral Sclerosis (SEALS) population register. Patients were randomly allocated to 'discovery' or 'test' cohorts. A prognostic score was calculated using the discovery cohort and then used to predict survival in the test cohort. The score was used as a predictor variable to split the test cohort in four prognostic categories (good, moderate, average, poor). The accuracy of the score in predicting survival was tested by checking whether the predicted survival fell within the actual survival tertile which that patient was in. A prognostic score generated from one cohort of patients predicted survival for a second cohort of patients (r(2) = 0.72). Six variables were included in the survival model: age at onset, diagnostic delay, El Escorial category, use of riluzole, gender and site of onset. Cox regression demonstrated a strong relationship between these variables and survival (chi(2) 80.8, df 1, p < 0.0001, n = 343) in the test cohort. Kaplan-Meier analysis demonstrated a significant difference in survival between clinical categories (log rank 161.932, df 3, p < 0.001), and the prognostic score generated for the test cohort accurately predicted survival in 64% of the patients. In conclusion, it is possible to correctly classify patients into prognostic categories using clinical data easily available at time of diagnosis. PMID- 22670881 TI - Novel G37V mutation of SOD1 gene in autopsied patient with familial amyotrophic lateral sclerosis. AB - We report a novel missense mutation (G37V) in exon 2 of the superoxide dismutase 1 gene in a 63-years-old Japanese male with purely lower motor neuron disease. His disease duration was 14 months, and he died of respiratory failure. The disease in this patient with the G37V mutation showed a rapid progression, although patients with G37R mutation are known to have a long survival. PMID- 22670882 TI - Trismus as the first symptom of amyotrophic lateral sclerosis. AB - We report the case of a 75-year-old female who had a trismus as the first, long lasting and, isolated symptom of ALS. We discuss also therapeutic possibilities. PMID- 22670883 TI - Electrical impedance myography as a biomarker to assess ALS progression. AB - Electrical impedance myography (EIM), a non-invasive, electrophysiological technique, has preliminarily shown value as an ALS biomarker. Here we perform a multicenter study to further assess EIM's potential for tracking ALS. ALS patients were enrolled across eight sites. Each subject underwent EIM, handheld dynamometry (HHD), and the ALS Functional Rating Scale-revised (ALSFRS-R) regularly. Techniques were compared by assessing the coefficient of variation (CoV) in the rate of decline and each technique's correlation to survival. Results showed that in the 60 patients followed for one year, EIM phase measured from the most rapidly progressing muscle in each patient had a CoV in the rate of decline of 0.62, compared to HHD (0.82) and the ALSFRS-R (0.74). Restricting the measurements to the first six months gave a CoV of 0.55 for EIM, 0.93 for HHD, and 0.84 for ALSFRS-R. For both time-periods, all three measures correlated with survival. Based on these data, a six-month clinical trial designed to detect a 20% treatment effect with 80% power using EIM would require only 95 patients/arm compared to the ALSFRS-R, which would require 220 subjects/arm. In conclusion, EIM can serve as a useful ALS biomarker that offers the prospect of greatly accelerating phase 2 clinical trials. PMID- 22670884 TI - Factors influencing burden among non-professional immigrant caregivers: a case control study. AB - AIM: To identify factors related to the burden that is experienced by untrained immigrant caregivers. BACKGROUND: There is growing concern about how to provide the care required by an ageing population. Although elder care has usually been provided by family members, this role is increasingly being fulfilled by immigrant caregivers with no formal training. DESIGN: Case-control study (burdened/non-burdened according to the Zarit Burden Interview). METHODS: The study took place between May 2005-October 2009. Anonymous questionnaires were distributed to 110 immigrant caregivers and their corresponding older care recipients (n = 110), who were receiving care in their homes in Barcelona (Spain). The questionnaires included measures of burden, social support, quality of life and social integration, and items about the physical/psychological status of the care recipient and the nature of the care tasks. Two groups of immigrant caregivers were defined according to their scores on the Zarit Burden Interview: burdened (n = 55) and non-burdened (n = 55). RESULTS: Burdened caregivers reported less social support, a poorer quality of life, and problems with social integration. Furthermore, 48% said that they lacked knowledge about the care task, while 44% had difficulty performing certain care tasks, which constitutes a risk situation. CONCLUSION: Burden among untrained immigrant caregivers may be reduced by improving their social support systems and quality of life, thereby helping to ensure the availability of the caregiver services, which society increasingly needs. PMID- 22670885 TI - Turnover numbers, turnover frequencies, and overpotential in molecular catalysis of electrochemical reactions. Cyclic voltammetry and preparative-scale electrolysis. AB - The search for efficient catalysts to face modern energy challenges requires evaluation and comparison through reliable methods. Catalytic current efficiencies may be the combination of many factors besides the intrinsic chemical properties of the catalyst. Defining turnover number and turnover frequency (TOF) as reflecting these intrinsic chemical properties, it is shown that catalysts are not characterized by their TOF and their overpotential (eta) as separate parameters but rather that the parameters are linked together by a definite relationship. The log TOF-eta relationship can often be linearized, giving rise to a Tafel law, which allows the characterization of the catalyst by the value of the TOF at zero overpotential (TOF(0)). Foot-of-the-wave analysis of the cyclic voltammetric catalytic responses allows the determination of the TOF, log TOF-eta relationship, and TOF(0), regardless of the side-phenomena that interfere at high current densities, preventing the expected catalytic current plateau from being reached. Strategies for optimized preparative-scale electrolyses may then be devised on these bases. The validity of this methodology is established on theoretical grounds and checked experimentally with examples taken from the catalytic reduction of CO(2) by iron(0) porphyrins. PMID- 22670886 TI - A study of the chemical and biological stability of vasoactive intestinal peptide. AB - CONTEXT: Vasoactive intestinal peptide (VIP) is a linear cationic neuropeptide composed of 28 amino acids. It belongs to the glucagon/secretin family. The biological functions of VIP are relatively broad, but it has not been well studied in the field of pharmaceutics. Especially in the selection of the way of VIP administration and the pharmaceutical formulation, the theory basis was deficient appreciably. OBJECTIVE: To provide the theory basis for the pharmaceutical development of VIP, the chemical and biological stability of VIP was studied. MATERIALS AND METHODS: The stability of VIP in different pH values, ionic strength, temperature, artificial gastric fluid and artificial intestinal fluid was investigated, and the concentration of VIP was calculated by HPLC method. RESULTS: The stability of VIP was pH-dependent. VIP was stable in acid and neutral solution, and almost didn't degrade during pH <= 7 solution. However, it was instability in basic solution and degraded completely at 30 min in pH 13 solution. Ionic strength did not affect its stability. VIP was stable in freezing conditions but it degraded at low concentration in cold storage. Furthermore, VIP degraded so quickly in artificial gastric fluid and artificial intestinal fluid that it can't be detected at 0 min. DISCUSSION AND CONCLUSION: the chemical and biological characteristic of VIP was unstable, so it isn't suitable for oral administration. PMID- 22670887 TI - Leaving nothing to chance: how to randomize a clinical trial. PMID- 22670888 TI - Establishment of an ex vivo pulpitis model by co-culturing immortalized dental pulp cells and macrophages. AB - AIM: To establish an ex vivo pulpitis model by co-culturing dental pulp cells with macrophages. METHODOLOGY: As dental pulp cells, immortalized human dental pulp cells, named DP-1, were used, whilst as macrophage cell lines, the differentiated human monocytic cell line, THP-1, was used. In some experiments, primary dental pulp cells were isolated and used to confirm the results obtained in the experiments using immortalized cells. Co-culturing was performed using transwell systems. Inflammatory responses were evaluated by measuring cytokines produced by the cells. RESULTS: Co-culturing both cell types markedly up regulated inflammatory cytokine production as compared with the cells cultured independently, suggesting that both cell types interact with each other to synergistically produce higher amounts of inflammatory cytokines. Interestingly, both DP-1 and primary dental pulp cells appeared to produce molecules stimulating macrophages to produce tumour necrosis factor-alpha-. CONCLUSION: Co-culturing immortalized dental pulp cells and macrophages may be a new ex vivo model for studying the pathophysiology of reversible pulpitis. PMID- 22670889 TI - Rapid microbial quantification of disinfected contact lens surfaces. AB - AIM: The efficacy of disinfection of contact lenses is difficult to determine. We have monitored microbial contamination on surfaces and in fluids by intrinsic fluorescence of microbes and distinguished their metabolic states (viable cells, nonviable cells, and endospores). This approach is sensitive (10 cells), requires no added reagents or sample contact, and measurements can be made in near real time. The disinfection performance of AMO Easy RubTM and Alcon No RubTM contact lens solutions was compared with CVS-brand saline for contact lenses on contact lenses contaminated with Pseudomonas aeruginosa (ATCC 10145). Our aim is to show that intrinsic fluorescence measurements can yield real-time, critical information about the efficacy of contact lens decontamination products and protocols. MATERIALS AND METHODS: Intrinsic fluorescence of AcuvueTM contact lenses (samples and controls) was measured before and after incubation with P. aeruginosa. Inoculated lenses were then cleaned and disinfected, according to directions for AMO Easy RubTM and Alcon No RubTM, rubbed and rinsed with saline for contact lenses (the brand made a difference in the experiment), followed by measurement of the effectiveness of the disinfection procedure with the intrinsic fluorescence instrument. Both the sample lenses after disinfection and the control lenses were immediately placed in LB broth for outgrowth and measured by standard cell-counting methods. The experiments were performed in triplicate. RESULTS: The concentration of P. aeruginosa formed on the lenses by the above methods varied from 10(6)-10(13) cells/mL. All lenses that were cultured following cleaning yielded no colonies. However, 10(5)-10(9) cells/mL of the bacteria on the treated lenses remained viable when analyzed by intrinsic fluorescence methodology. CONCLUSIONS: These results indicate that a medically significant amount of bacteria remained on the contact lenses after disinfection and/or cleaning, which were viable but nonculturable and are likely to go undetected when using standard culture methods. PMID- 22670890 TI - Efficacy of collagenase in patients who did and did not have previous hand surgery for Dupuytren's contracture. AB - Collagenase Clostridium histolyticum (CCH) is a non-surgical, efficacious therapy for Dupuytren's contracture (DC). This study evaluated the efficacy and safety of CCH in patients with previous DC surgery. Data from 12 CCH clinical trials were pooled. At screening, patients provided details about the type/date of previous DC surgery. Reviewers coded descriptions to the Operated Hand, finger, and joint. Of 1082 patients, 422 (39%) had previous DC surgery. For these patients with previous surgery, the CCH treatment was coded on the Operated (n = 206) or Non operated Hand (n = 196). End-points included changes in fixed-flexion contracture (FFC) and range of motion (ROM). Adverse events (AEs) were monitored. After treatment with CCH, FFC at metacarpophalangeal joints was reduced by 75% in previously Operated Hands and by 80% for Non-operated Hands (p = 0.6). Improvements in ROM were 32 degrees and 32 degrees , respectively (p = 0.9). For proximal inter-phalangeal joints, the reductions in FFC for the Operated and Non operated Hands were 52% and 50%, respectively (p = 0.6); improvements in ROM were 24 degrees and 26 degrees , respectively (p = 0.3). Some AE rates were significantly higher in the Operated vs Non-operated Hand groups, but were not clinically relevant. There were no between-group significant differences in AE duration (p > 0.08). Previous surgery for DC does not affect efficacy or safety of CCH, suggesting CCH is an option in patients with recurring DC. Some AE rates were significantly higher, but not clinically relevant. PMID- 22670892 TI - The development & evaluation of two vision screening tools for correctable visual loss in older people. AB - OBJECTIVES: In the UK, 20-50% of older people have undetected reduced vision and in most cases this results from correctable problems (refractive error and cataract). Many older people are not availing themselves of state-funded community optometric care. We assessed the efficacy of two vision screening instruments at detecting correctable visual problems and investigated the effect of optometric intervention on quality of life. METHODS: A computerised vision screener (CVS) was developed and refined after a preliminary study of 180 older people to include tests of: monocular presenting distance high contrast and low contrast visual acuities (VAs), binocular near acuities, and monocular visual fields. The modified CVS and a flip-chart vision screener (FVS) were evaluated on a second sample of 200 people aged 65+ (mean age 77 years). All participants in both studies were given an optometric eye examination, including high and low contrast VAs, refraction, binocular vision tests, tonometry, automated perimetry, and dilated fundoscopy including cataract grading and ARM grading. The target conditions were significant gain in monocular distance VA or binocular near VA with new refractive correction, significant cataract, or macular degeneration at risk of rapid progression. The Low Vision Quality of Life Questionnaire (LVQoL) was administered before and up to 3 months after testing. RESULTS: For the CVS, the best sensitivity (80.3%, 95% CI 72.4-86.4; specificity 66.7%, 95% CI 55.6 76.1) was obtained for a screener test combination of a fail on high contrast VA (>0.19 LogMAR) OR low contrast VA (>0.39 LogMAR) OR near VA (>N11.9). A screener test combination of high contrast VA OR near VA gave sensitivity of 79.5% (71.5 85.7) and specificity 67.9% (57-77.3). For the FVS, the best sensitivity was obtained for a test combination of a fail on high contrast VA OR low contrast VA OR near VA (sensitivity 82%, 95% CI 74.2-87.8; specificity 61.5%, 95% CI 50.4 71.6). A screener test combination of low contrast VA alone gave sensitivity of 75.4% (67.1-82.2) and specificity 76.9% (66.4-84.9). Significant improvements in LVQoL were found, with a significant correlation between gain in VA with new spectacles and improvement in LVQoL. CONCLUSIONS: The vision screeners are effective tools for detecting those with reduced vision. Further work is required to determine their effectiveness as a tool for encouraging older people to engage in regular eyecare. PMID- 22670891 TI - Effects of season and experimental warming on the bacterial community in a temperate mountain forest soil assessed by 16S rRNA gene pyrosequencing. AB - Climate warming may induce shifts in soil microbial communities possibly altering the long-term carbon mineralization potential of soils. We assessed the response of the bacterial community in a forest soil to experimental soil warming (+4 degrees C) in the context of seasonal fluctuations. Three experimental plots were sampled in the fourth year of warming in summer and winter and compared to control plots by 16S rRNA gene pyrosequencing. We sequenced 17,308 amplicons per sample and analysed operational taxonomic units at genetic distances of 0.03, 0.10 and 0.25, with respective Good's coverages of 0.900, 0.977 and 0.998. Diversity indices did not differ between summer, winter, control or warmed samples. Summer and winter samples differed in community structure at a genetic distance of 0.25, corresponding approximately to phylum level. This was mainly because of an increase of Actinobacteria in winter. Abundance patterns of dominant taxa (> 0.06% of all reads) were analysed individually and revealed, that seasonal shifts were coherent among related phylogenetic groups. Seasonal community dynamics were subtle compared to the dynamics of soil respiration. Despite a pronounced respiration response to soil warming, we did not detect warming effects on community structure or composition. Fine-scale shifts may have been concealed by the considerable spatial variation. PMID- 22670893 TI - Template induced conformational change of amyloid-beta monomer. AB - Population of aggregation-prone conformers for the monomeric amyloid-beta (Abeta) can dramatically speed up its fibrillar aggregation. In this work, we study the effect of preformed template on the conformational distributions of the monomeric Abeta by replica exchange molecular dynamics. Our results show that the template consisting of Abeta peptides with cross-beta structure can induce the formation of beta-rich conformations for the monomeric Abeta, which is the key feature of the aggregation-prone conformers. Similar effect is observed when the hIAPP peptides and poly alanine peptides were used as templates, suggesting that the template effect is insensitive to the sequence details of the template peptides. In comparison, the template with helical structure has no significant effects on the beta-propensity of the monomeric Abeta. Analysis to the interaction details revealed that the template tends to disrupt the intrapeptide interactions of the monomeric Abeta, which are absent in the fibrillar state, suggesting that the preformed template can reorganize the intrapeptide interactions of the monomeric Abeta during the capturing stage and reduce the energy frustrations for the fibrillar aggregations. PMID- 22670894 TI - Osteopathia striata congenita with cranial sclerosis and intellectual disability due to contiguous gene deletions involving the WTX locus. AB - Osteopathia striata congenita with cranial sclerosis (OSCS) is a skeletal dysplasia caused by germline deletions of or truncating point mutations in the X linked gene WTX (FAM123B, AMER1). Females present with longitudinal striations of sclerotic bone along the long axis of long bones and cranial sclerosis, with a high prevalence of cleft palate and hearing loss. Intellectual disability or neurodevelopmental delay is not observed in females with point mutations in WTX leading to OSCS. One female has been described with a deletion spanning multiple neighbouring genes suggesting that deletion of some neighbouring loci may result in abnormal neurodevelopment. In this cohort of 13 females with OSCS resulting from deletions of WTX, a relationship is observed where deletion of ARHGEF9 and/or MTMR8 in conjunction with WTX results in an additional neurodevelopmental phenotype whereas deletion of ASB12 along with WTX is associated with a good neurodevelopmental prognosis. PMID- 22670895 TI - Comparison between famciclovir and valacyclovir for acute pain in adult Japanese immunocompetent patients with herpes zoster. AB - Famciclovir is a guanine analog antiviral drug used commonly for herpes zoster. Efficacy of famciclovir treatment has been reported to be comparable to valacyclovir treatment. Both of these medications reduce the time to complete cessation of zoster-associated pain including post-herpetic neuralgia, as compared to acyclovir. We conducted a multicenter, randomized, open clinical trial in order to evaluate the extent of pain relief afforded by these two antiviral drugs during the acute disease phase of herpes zoster. The study group comprised 86 immunocompetent adult patients suffering from herpes zoster, who were treated with either famciclovir or valacyclovir for 7 days. Of these, 55 patients enrolled in this study within 72 h of the onset of the rash and 31 patients after 72 h of the onset. There was a significant reduction in acute herpes zoster pain with famciclovir on day 7 and at 2-3 weeks in both of these patient groups, while with valacyclovir, there was not significant reduction in pain on day 7. Of patients aged 50 years or older, there was a significantly earlier reduction in pain with famciclovir than with valacyclovir. In addition, a significant reduction in the number of patients with pain was observed as early as days 3-4 with famciclovir treatment as compared with valacyclovir treatment. We conclude that famciclovir was superior to valacyclovir in the relief of acute pain of herpes zoster. Accordingly, famciclovir is recommended for herpes zoster patients with moderate symptoms and a visual analog scale score of under 50 mm. PMID- 22670896 TI - TFD: Torsion Fingerprints as a new measure to compare small molecule conformations. AB - Advantages like intuitive interpretation, objectivity, general applicability, and its easy, automated calculation make the rmsd (root-mean-squared deviation) the measure of choice for the investigation of the accuracy of conformational model generators. For comparing conformations of a single molecule this is a clearly superior method. Single molecule analysis is, however, a rare scenario. Typically, conformations are generated for huge corporate or external vendor databases of high diversity which are then further investigated with high throughput computational methods like docking or pharmacophore searching, in virtual screening campaigns. Representative subsets for accuracy investigations of computational methods need to mimic this diversity. Averaged rmsd values over these data sets are frequently used to assess the accuracy of the methods. There are, however, significant weaknesses in rmsd comparisons for such kind of data sets. The interpretation is for example no longer intuitive because what can be expected in terms of good or bad rmsd values crucially depends on the data set composition like size or number of rotatable bonds of the underlying molecules. Further, rmsd lacks normalization which might result in very high averaged rmsd values for highly flexible molecules and thus might completely skew results. We have developed a novel measure to compare conformations of molecules called Torsion Fingerprint Deviation (TFD). It extracts, weights, and compares Torsion Fingerprints from a query molecule and generated conformations under consideration of acyclic bonds as well as ring systems. TFD is alignment-free and overcomes major limitations of rmsd while retaining its advantages. PMID- 22670898 TI - Synthesis, structures, and properties of two three-dimensional metal-organic frameworks, based on concurrent ligand extension. AB - A tritopic carboxylate ligand, tris(4'-carboxybiphenyl)amine (L-H(3)), has been synthesized and applied in the construction of microporous metal-organic frameworks (MOFs). Two novel metal-organic frameworks (MOFs), {[Zn(2)(L)(OH)].2DMF.H(2)O}(infinity) (1) and {[Cu(L H)(DMA)].DMA.2H(2)O}(infinity) (2), have been constructed out of L-H(3), Zn(2+), and Cu(2+), respectively. 1 has a 2-fold interpenetrating three-dimensional framework formed by L connectors and the [Zn(2)(CO(2))(3)] secondary building units (SBUs). As for 1, it is worth pointing out that one MU(2)-OH group links two Zn atoms between two neighboring SBUs to produce interesting Zn-O-Zn zigzag chains in the structure. 2 has a two-dimensional grid sheet formed by L-H connectors and the typical paddle-wheel [Cu(2)(CO(2))(4)] SBUs. Two-dimensional (2D) sheets nest with each other, which finally forms a three-dimensional (3D) nested framework. Two MOFs are characterized by infrared (IR) spectroscopy, thermogravimetry, single-crystal and elemental analyses, and powder X-ray diffraction methods. Framework 1' exhibits high permanent porosity (Langmuir surface area = 848 m(2)/g), high thermal stability (up to 450 degrees C), highly active properties for Friedel-Crafts alkylation reaction, as well as the potential application for the CO(2) gas storage and luminescent material. The catalytic results reveal that 2' is indeed an efficient heterogeneous catalyst for olefin epoxidation reactions. PMID- 22670899 TI - Spatiotemporal regulation of PKC via interactions with AKAP7 isoforms. AB - The regulation of kinases by scaffolding proteins greatly contributes to the fidelity of signal transduction. In the present study, we explored an interaction between the ubiquitous enzyme PKC (protein kinase C) and the scaffolding protein AKAP7 (A-kinase-anchoring protein 7). Using protein biochemistry and surface plasmon resonance approaches, we demonstrate that both AKAP7gamma and AKAP7alpha are capable of high-affinity interactions with multiple isoenzymes of PKC. Furthermore, this interaction is achieved via multi-site binding on both proteins. FRET (fluorescence resonance energy transfer) analysis using a PKC activity reporter suggests that anchoring of the kinase within AKAP7 complexes enhances the phosphorylation of substrate proteins. Finally, we determined using FRAP (fluorescence recovery after photobleaching) and virtual modelling that AKAP7 restricts the mobility of PKC within cells by tethering it to subcellular compartments. Collectively, the results of the present study suggests that AKAP7 could play an integral role in dictating PKC localization and function in tissues where the two proteins are co-expressed. PMID- 22670900 TI - Two hundred years of hospital costs and mortality--MGH and four eras of value in medicine. PMID- 22670901 TI - Delamanid for multidrug-resistant pulmonary tuberculosis. AB - BACKGROUND: Delamanid (OPC-67683), a nitro-dihydro-imidazooxazole derivative, is a new antituberculosis medication that inhibits mycolic acid synthesis and has shown potent in vitro and in vivo activity against drug-resistant strains of Mycobacterium tuberculosis. METHODS: In this randomized, placebo-controlled, multinational clinical trial, we assigned 481 patients (nearly all of whom were negative for the human immunodeficiency virus) with pulmonary multidrug-resistant tuberculosis to receive delamanid, at a dose of 100 mg twice daily (161 patients) or 200 mg twice daily (160 patients), or placebo (160 patients) for 2 months in combination with a background drug regimen developed according to World Health Organization guidelines. Sputum cultures were assessed weekly with the use of both liquid broth and solid medium; sputum-culture conversion was defined as a series of five or more consecutive cultures that were negative for growth of M. tuberculosis. The primary efficacy end point was the proportion of patients with sputum-culture conversion in liquid broth medium at 2 months. RESULTS: Among patients who received a background drug regimen plus 100 mg of delamanid twice daily, 45.4% had sputum-culture conversion in liquid broth at 2 months, as compared with 29.6% of patients who received a background drug regimen plus placebo (P=0.008). Likewise, as compared with the placebo group, the group that received the background drug regimen plus 200 mg of delamanid twice daily had a higher proportion of patients with sputum-culture conversion (41.9%, P=0.04). The findings were similar with assessment of sputum-culture conversion in solid medium. Most adverse events were mild to moderate in severity and were evenly distributed across groups. Although no clinical events due to QT prolongation on electrocardiography were observed, QT prolongation was reported significantly more frequently in the groups that received delamanid. CONCLUSIONS: Delamanid was associated with an increase in sputum-culture conversion at 2 months among patients with multidrug-resistant tuberculosis. This finding suggests that delamanid could enhance treatment options for multidrug-resistant tuberculosis. (Funded by Otsuka Pharmaceutical Development and Commercialization; ClinicalTrials.gov number, NCT00685360.). PMID- 22670902 TI - National survey of drug-resistant tuberculosis in China. AB - BACKGROUND: The available information on the epidemic of drug-resistant tuberculosis in China is based on local or regional surveys. In 2007, we carried out a national survey of drug-resistant tuberculosis in China. METHODS: We estimated the proportion of tuberculosis cases in China that were resistant to drugs by means of cluster-randomized sampling of tuberculosis cases in the public health system and testing for resistance to the first-line antituberculosis drugs isoniazid, rifampin, ethambutol, and streptomycin and the second-line drugs ofloxacin and kanamycin. We used the results from this survey and published estimates of the incidence of tuberculosis to estimate the incidence of drug resistant tuberculosis. Information from patient interviews was used to identify factors linked to drug resistance. RESULTS: Among 3037 patients with new cases of tuberculosis and 892 with previously treated cases, 5.7% (95% confidence interval [CI], 4.5 to 7.0) and 25.6% (95% CI, 21.5 to 29.8), respectively, had multidrug resistant (MDR) tuberculosis (defined as disease that was resistant to at least isoniazid and rifampin). Among all patients with tuberculosis, approximately 1 of 4 had disease that was resistant to isoniazid, rifampin, or both, and 1 of 10 had MDR tuberculosis. Approximately 8% of the patients with MDR tuberculosis had extensively drug-resistant (XDR) tuberculosis (defined as disease that was resistant to at least isoniazid, rifampin, ofloxacin, and kanamycin). In 2007, there were 110,000 incident cases (95% CI, 97,000 to 130,000) of MDR tuberculosis and 8200 incident cases (95% CI, 7200 to 9700) of XDR tuberculosis. Most cases of MDR and XDR tuberculosis resulted from primary transmission. Patients with multiple previous treatments who had received their last treatment in a tuberculosis hospital had the highest risk of MDR tuberculosis (adjusted odds ratio, 13.3; 95% CI, 3.9 to 46.0). Among 226 previously treated patients with MDR tuberculosis, 43.8% had not completed their last treatment; most had been treated in the hospital system. Among those who had completed treatment, tuberculosis developed again in most of the patients after their treatment in the public health system. CONCLUSIONS: China has a serious epidemic of drug-resistant tuberculosis. MDR tuberculosis is linked to inadequate treatment in both the public health system and the hospital system, especially tuberculosis hospitals; however, primary transmission accounts for most cases. (Funded by the Chinese Ministry of Health.). PMID- 22670903 TI - Efficacy and safety of vismodegib in advanced basal-cell carcinoma. AB - BACKGROUND: Alterations in hedgehog signaling are implicated in the pathogenesis of basal-cell carcinoma. Although most basal-cell carcinomas are treated surgically, no effective therapy exists for locally advanced or metastatic basal cell carcinoma. A phase 1 study of vismodegib (GDC-0449), a first-in-class, small molecule inhibitor of the hedgehog pathway, showed a 58% response rate among patients with advanced basal-cell carcinoma. METHODS: In this multicenter, international, two-cohort, nonrandomized study, we enrolled patients with metastatic basal-cell carcinoma and those with locally advanced basal-cell carcinoma who had inoperable disease or for whom surgery was inappropriate (because of multiple recurrences and a low likelihood of surgical cure, or substantial anticipated disfigurement). All patients received 150 mg of oral vismodegib daily. The primary end point was the independently assessed objective response rate; the primary hypotheses were that the response rate would be greater than 20% for patients with locally advanced basal-cell carcinoma and greater than 10% for those with metastatic basal-cell carcinoma. RESULTS: In 33 patients with metastatic basal-cell carcinoma, the independently assessed response rate was 30% (95% confidence interval [CI], 16 to 48; P=0.001). In 63 patients with locally advanced basal-cell carcinoma, the independently assessed response rate was 43% (95% CI, 31 to 56; P<0.001), with complete responses in 13 patients (21%). The median duration of response was 7.6 months in both cohorts. Adverse events occurring in more than 30% of patients were muscle spasms, alopecia, dysgeusia (taste disturbance), weight loss, and fatigue. Serious adverse events were reported in 25% of patients; seven deaths due to adverse events were noted. CONCLUSIONS: Vismodegib is associated with tumor responses in patients with locally advanced or metastatic basal-cell carcinoma. (Funded by Genentech; Erivance BCC ClinicalTrials.gov number, NCT00833417.). PMID- 22670905 TI - Clinical practice. Acute limb ischemia. PMID- 22670904 TI - Inhibiting the hedgehog pathway in patients with the basal-cell nevus syndrome. AB - BACKGROUND: Dysregulated hedgehog signaling is the pivotal molecular abnormality underlying basal-cell carcinomas. Vismodegib is a new orally administered hedgehog-pathway inhibitor that produces objective responses in locally advanced and metastatic basal-cell carcinomas. METHODS: We tested the anti-basal-cell carcinoma efficacy of vismodegib in a randomized, double-blind, placebo controlled trial in patients with the basal-cell nevus syndrome at three clinical centers from September 2009 through January 2011. The primary end point was reduction in the incidence of new basal-cell carcinomas that were eligible for surgical resection (surgically eligible) with vismodegib versus placebo after 3 months; secondary end points included reduction in the size of existing basal cell carcinomas. RESULTS: In 41 patients followed for a mean of 8 months (range, 1 to 15) after enrollment, the per-patient rate of new surgically eligible basal cell carcinomas was lower with vismodegib than with placebo (2 vs. 29 cases per group per year, P<0.001), as was the size (percent change from baseline in the sum of the longest diameter) of existing clinically significant basal-cell carcinomas (-65% vs. -11%, P=0.003). In some patients, all basal-cell carcinomas clinically regressed. No tumors progressed during treatment with vismodegib. Patients receiving vismodegib routinely had grade 1 or 2 adverse events of loss of taste, muscle cramps, hair loss, and weight loss. Overall, 54% of patients (14 of 26) receiving vismodegib discontinued drug treatment owing to adverse events. At 1 month, vismodegib use had reduced the hedgehog target-gene expression by basal-cell carcinoma by 90% (P<0.001) and diminished tumor-cell proliferation, but apoptosis was not affected. No residual basal-cell carcinoma was detectable in 83% of biopsy samples taken from sites of clinically regressed basal-cell carcinomas. CONCLUSIONS: Vismodegib reduces the basal-cell carcinoma tumor burden and blocks growth of new basal-cell carcinomas in patients with the basal-cell nevus syndrome. The adverse events associated with treatment led to discontinuation in over half of treated patients. (Funded by Genentech and others; ClinicalTrials.gov number, NCT00957229.). PMID- 22670906 TI - Images in clinical medicine. Scrofuloderma. PMID- 22670907 TI - Clinical problem-solving. The wolf at the door. PMID- 22670908 TI - Confronting multidrug-resistant tuberculosis. PMID- 22670909 TI - Oral hedgehog-pathway inhibitors for basal-cell carcinoma. PMID- 22670911 TI - Discontinuing donepezil or starting memantine for Alzheimer's disease. PMID- 22670912 TI - Discontinuing donepezil or starting memantine for Alzheimer's disease. PMID- 22670914 TI - Prostate-cancer mortality after PSA screening. PMID- 22670915 TI - Prostate-cancer mortality after PSA screening. PMID- 22670916 TI - Prostate-cancer mortality after PSA screening. PMID- 22670917 TI - Prostate-cancer mortality after PSA screening. PMID- 22670919 TI - Genomics, intellectual disability, and autism. PMID- 22670921 TI - What's the alternative? PMID- 22670922 TI - Translocation affecting sonic hedgehog genes in basal-cell carcinoma. PMID- 22670923 TI - Images in clinical medicine. Bladder stone. PMID- 22671019 TI - A curious serendipitous finding: Spitz naevus combined with a syringoma. AB - Combined tumours are often a serendipitous finding. Among the spectrum of melanocytic tumours, the co-existence of different cell populations of the same lineage is a well-recognised phenomenon. Less commonly documented, but still well documented is the event of a melanocytic tumour in collision with an epithelial benign or malignant neoplasm. Exceptionally infrequent is however the collision of a Spitz naevus with an epithelial tumour. Here we report the clinical dermoscopic and histopathological findings of a Spitz naevus occurring in collision with a syringoma. PMID- 22671021 TI - A prospective study to assess the palatability of analgesic medicines in children. AB - AIM: This study examined children's opinions on the taste of three analgesic medicines: paracetamol, ibuprofen and codeine. BACKGROUND: Many medicines for children are unpleasant and unacceptable. Research has shown that children's taste preferences differ to adults, in whom palatability is often tested. Little British research exists on children's opinions on the palatability of medicines. This study aimed to address this gap in knowledge. DESIGN: Prospective observational study. METHODS: Between May-September 2008, hospital inpatients aged 5-16 years rated the taste of required analgesics on a 100-mm visual analogue scale. This incorporated a 5-point facial hedonic scale. They were also asked their favourite flavour and colour for a medicine. RESULTS: A total of 159 children took part. Eighty-five males (53.5%) and 74 females (46.5%). The median age was 8 years (Inter-quartile range 6-11). The taste of ibuprofen was significantly preferred to paracetamol or codeine. Significant differences were observed depending if the medicine rated was taken first or second (for example pre-medication with paracetamol and ibuprofen). Younger children (5-8 years) were more likely to choose the extremes of the scale when grading than older children were. Preferred flavours on questioning were strawberry 44% and banana 17%. Favourite colours were pink 25.8% and red 20.8%, with girls more likely to choose pink and boys blue. CONCLUSION: Ibuprofen was the most palatable analgesic medicine tested. Children reported they preferred fruit flavours and colour was sex dependent. Nurses when administering two medicines together should consider giving the least palatable first, for example paracetamol before ibuprofen for pre-medication. PMID- 22671022 TI - Three-component assembly of conjugated enyne scaffolds via E-selective olefination of ynals. AB - Benefited by the accessible ynamido-lithium intermediates Ib from a Cu-catalyzed azide-alkyne cycloaddition in the presence of stoichiometric amounts of LiOH, a mild and flexible three-component route to conjugated enyne scaffolds was successfully achieved via a formal E-selective olefination strategy. PMID- 22671024 TI - Leaf gas exchange and oxidative stress in sorghum plants supplied with silicon and infected by Colletotrichum sublineolum. AB - Considering the economic importance of anthracnose, caused by Colletotrichum sublineolum, and silicon (Si) to enhance sorghum resistance against this disease, this study aimed to investigate the effect of this element on leaf gas exchange and also the antioxidative system when infected by C. sublineolum. Plants from sorghum line CMSXS142 (BR 009 [Tx623] - Texas), growing in hydroponic culture with (+Si, 2 mM) or without (-Si) Si, were inoculated with C. sublineolum. Disease severity was assessed at 2, 4, 6, 8, and 10 days after inoculation (dai) and data were used to calculate the area under anthracnose progress curve (AUAPC). Further, the net carbon assimilation rate (A), stomatal conductance to water vapor (g(s)), internal-to-ambient CO2 concentration ratio (C(i)/C(a)), and transpiration rate (E); the activities of superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), and glutathione reductase (GR); the electrolyte leakage (EL), and the concentrations of hydrogen peroxide (H2O2) and malondialdehyde (MDA) were determined. The AUAPC was reduced by 86% for the +Si plants compared with the -Si plants. The values of A, g(s), and E were lower upon inoculation of -Si plants in contrast to inoculated +Si plants with decreases of 31 and 60% for A, 34 and 61% for g(s), and 27 and 57% for E, respectively, at 4 and 8 dai. For the noninoculated plants, there was no significant difference between the -Si and +Si treatments for the values of A, g(s), and E. The C(i)/C(a) ratio was similar between the -Si and +Si treatments, regardless of the pathogen inoculation. The activities of SOD, CAT, APX, and GR tended to be higher in the +Si plants compared with the -Si plants upon inoculation with C. sublineolum. The EL significantly increased for -Si plants compared with +Si plants. The MDA concentration significantly increased by 31 and 38% at 4 and 8 dai, respectively, for the -Si plants compared with the +Si plants. Based on these results, Si may have a positive effect on sorghum physiology when infected by C. sublineolum through the maintenance of carbon fixation and also by enhancing the antioxidant system, which resulted in an increase in reactive oxygen species scavenging and, ultimately, reduced damage to the cell membranes. PMID- 22671026 TI - An optimized duplex real-time PCR tool for sensitive detection of the quarantine oomycete Plasmopara halstedii in sunflower seeds. AB - Plasmopara halstedii, the causal agent of downy mildew of sunflower, is an oomycete listed as a quarantine pathogen. This obligate parasite resides in a quiescent state in seeds of sunflower and can be spread from seed production areas to areas of crop production by international seed trade. To prevent the spread or the introduction of potentially new genotypes or fungicide-tolerant strains, an efficient method to detect P. halstedii in sunflower seed is required. This work reports the optimization of a real-time detection tool that targets the pathogen within sunflower seeds, and provides statistically validated data for that tool. The tool proved to be specific and inclusive, based on computer simulation and in vitro assessments, and could detect as few as 45 copies of target DNA. A fully optimized DNA extraction protocol was also developed starting from a sample of 1,000 sunflower seeds, and enabled the detection of <1 infected seed/1,000 seeds. To ensure reliability of the results, a set of controls was used systematically during the assays, including a plant specific probe used in a duplex quantitative polymerase chain reaction that enabled the assessment of the quality of each DNA extract. PMID- 22671023 TI - Strategy of lipid recognition by invariant natural killer T cells: 'one for all and all for one'. AB - Invariant natural killer T (iNKT) cells are evolutionarily conserved lipid reactive T cells that bridge innate and adaptive immune responses. Despite a relatively restricted T-cell receptor (TCR) diversity, these cells respond to a variety of structurally distinct foreign (i.e. microbial or synthetic) as well as host-derived (self-) lipid antigens presented by the CD1d molecule. These multi tasking lymphocytes are among the first responders in immunity, and produce an impressive array of cytokines and chemokines that can tailor the ensuing immune response. Accordingly, iNKT cells play important functions in autoimmune diseases, cancer, infection and inflammation. These properties make iNKT cells appealing targets in immune-based therapies. Yet, much has to be learned on the mechanisms that allow iNKT cells to produce polarized responses. Responses of iNKT cells are influenced by the direct signals perceived by the cells through their TCRs, as well as by indirect co-stimulatory (and potentially co-inhibitory) cues that they receive from antigen-presenting cells or the local milieu. A decade ago, biochemists and immunologists have started to describe synthetic lipid agonists with cytokine skewing potential, paving a new research avenue in the iNKT cell field. Yet how iNKT cells translate various antigenic signals into distinct functional responses has remained obscure. Recent findings have revealed a unique and innate mode of lipid recognition by iNKT cells, and suggest that both the lipid antigen presented and the diversity of the TCR modulate the strength of CD1d-iNKT TCR interactions. In this review, we focus on novel discoveries on lipid recognition by iNKT cells, and how these findings may help us to design effective strategies to steer iNKT cell responses for immune intervention. PMID- 22671027 TI - Grapevine phenolic compounds in xylem sap and tissues are significantly altered during infection by Xylella fastidiosa. AB - Pierce's disease of grapevine (PD), caused by the bacterial pathogen Xylella fastidiosa, remains a serious problem for grape production in California and elsewhere. This research examined induction of phenolic compounds in grapevines ('Thompson Seedless') infected with X. fastidiosa over a 6-month period. Two months postinoculation with X. fastidiosa, catechin, digalloylquinic acid, and astringin were found at greater levels in xylem sap; multiple catechins, procyanidins, and stilbenoids were found at greater levels in xylem tissues; and precursors to lignin and condensed tannins were found at greater levels in xylem cell walls. However, such large-scale inductions of phenolic compounds were not observed 4 months after inoculation. Six months after inoculation, infected plants had significantly reduced phenolic levels in xylem sap and tissues when compared with control plants, including lowered levels of lignin and condensed tannins. At 6 months, PD symptoms were severe in infected plants and most photosynthetic tissue was abscised. These results suggest that, even though grapevine hosts may initially respond to X. fastidiosa infections with increased production of phenolic compounds, ultimately, PD causes grapevines to enter a state of decline whereby diseased hosts no longer have the resources to support secondary metabolite production, including defense-associated phenolic compounds. PMID- 22671028 TI - Treatment of a crown-root fracture with intentional replantation - case report with 16-year follow-up. AB - AIM: To report the intentional replantation of a maxillary central incisor with a crown-root fracture. SUMMARY: An 11-year-old girl was referred to a paediatric clinic with an extensive crown-root fracture of the maxillary right central incisor (tooth 11) with pulp exposure. Radiographs revealed that tooth 11 had a periapical radiolucent lesion, which suggested pulpal necrosis. The treatment option chosen was planned extraction and immediate intentional replantation of tooth 11 in a more coronal position. Sixteen years after treatment, tooth 11 was aesthetically and functionally sound, suggesting that the treatment was successful. KEY LEARNING POINT: Intentional replantation may be considered as a treatment option for teeth with crown-root fractures. PMID- 22671029 TI - Modern stromatolite phototrophic communities: a comparative study of procaryote and eucaryote phototrophs using variable chlorophyll fluorescence. AB - Stromatolites are laminated organosedimentary structures formed by microbial communities, principally cyanobacteria although eucaryote phototrophs may also be involved in the construction of modern stromatolites. In this study, productivity and photophysiology of communities from stromatolites (laminated) and thrombolites (nonlaminated) were analysed using fluorescence imaging. Sub-samples of mats were excised at Highborne Cay, Bahamas, and cross-sectioned to simultaneously analyse surface, near-surface (1-2 mm), and deeper (2-10 mm) communities. Rapid light curve parameters and nonphotochemical downregulation showed distinct differences between phototroph communities, consistent with the reported quasi-succession of classic stromatolite mat types. Greater productivity was shown by cyanobacteria in Type 1 and Type 3 mats (first and final stage of the succession, Schizothrix gebeleinii and Solentia sp. respectively) and lower productivity within Type 2 mats (intermediate mat type). Eucaryote mat types, dominated by stalked (Striatella sp. and Licmophora sp.) and tube-dwelling (e.g. Nitzschia and Navicula spp.) diatoms, showed greater productivity than cyanobacteria communities, with the exception of Striatella (low productivity) and an unidentified coccoid cyanobacterium (high productivity). Findings indicate comparative variability between photosynthetically active procaryote and eucaryote sub-communities within stromatolites, with a pattern logically following the succession of 'classic' mat types, and lower than the productivity of eucaryote dominated 'nonclassic' mat types. PMID- 22671030 TI - Craniofacial variations in the tricho-dento-osseous syndrome. AB - Tricho-dento-osseous (TDO) syndrome is an autosomal dominant trait characterized by curly kinky hair at birth, enamel hypoplasia, taurodontism, thickening of cortical bones and variable expression of craniofacial morphology. Genetic studies have identified a 4-bp deletion in the DLX3 gene that is associated with TDO; however, phenotypic characterization and classification of TDO remains unclear in the literature. This study compares the craniofacial variations between 53 TDO-affected subjects and 34 unaffected family members. Standardized cephalograms were obtained and digitized. Cephalometric measurements were analyzed using a general linear model with family as a random effect. Numerous craniofacial measurements from both groups showed marked variability. TDO affected subjects showed a Class III skeletal pattern (smaller SNA and ANB angles), longer mandibular corpus length (GoGn) and shorter ramus height (p < 0.05). PMID- 22671031 TI - Effects of an anti-transforming growth factor-beta agent (pirfenidone) on strabismus surgery in rabbits. AB - PURPOSE: To evaluate the usefulness of an anti-transforming growth factor-beta (TGF-beta) agent, pirfenidone (PFD) on postoperative inflammation and fibrosis following strabismus surgery in rabbits. METHODS: Both eyes of 16 New Zealand white rabbits underwent reinsertion of the superior rectus muscle (SRM). After reinsertion of the SRM, PFD-loaded liposomes (0.5 mg/ml) were injected into the right eye (PFD group) and normal saline-loaded liposomes was injected into the left eye (control group), subconjunctivally (0.4 ml). To assess the postoperative inflammatory changes and fibrosis of the SRM, immunofluorescence staining with anti-CD11b antibody was performed at 3 days postoperatively, and Masson's trichrome staining was performed at 4 weeks postoperatively. To evaluate the toxicity of PFD on muscle fibers, the integrity of the muscle fibers was examined by transmission electron microscopy (TEM) at 3 days and 4 weeks postoperatively. RESULTS: CD11b protein expression was significantly reduced in the PFD group compared with the control group at 3 days postoperatively (p = 0.012). Masson trichrome staining, which stains collagen, was diminished in the PFD group at 4 weeks postoperatively. TEM revealed disorganized muscle fibers and vacuoles in both groups, but this was less prominent in the PFD group. CONCLUSIONS: Intraoperative injection of PFD may be effective as an adjunctive treatment to decrease inflammation and fibrosis resulting from strabismus surgery. PMID- 22671032 TI - Repeatability of corneal biomechanical measurements in children wearing spectacles and orthokeratology lenses. AB - PURPOSE: To determine the repeatability of corneal hysteresis (CH) and corneal resistance factor (CRF) measurements in children wearing spectacles and children under orthokeratology (ortho-k) therapy using the Ocular Response Analyzer (ORA). METHODS: CH and CRF were measured twice at a 10-min interval using ORA on the same day in both eyes of 25 children (mean age = 10.6 +/- 1.2 years) wearing spectacles and 34 children (mean age = 10.9 +/- 1.0 years) wearing ortho-k lenses. Four measurements were obtained from each eye in each set of measurements. Only data from the right eyes were analyzed. RESULTS: No significant between-measurement differences in CH and CRF were found in either group of subjects (paired t-tests, p > 0.05) and no correlations were found between the mean differences and their means (Pearson's correlations, -0.09 < r < 0.21, 0.24 < p < 0.85). The 95% limits of agreement (LA) were -1.87 mmHg to +2.59 mmHg and -1.53 mmHg to +1.41 mmHg for CH and -1.86 mmHg to +2.22 mmHg and -1.45 mmHg to +1.57 mmHg for CRF in the spectacle and ortho-k groups, respectively. A significant between-group difference in CRF was found (unpaired t-tests, p = 0.02). CONCLUSIONS: Repeatability of CH and CRF measurements using the ORA is within +/- 2 mmHg in children wearing spectacles or ortho-k lenses. We suggest that the ORA can be used to monitor long-term corneal biomechanical changes during ortho-k treatment. PMID- 22671033 TI - Recent progress in gene therapy for hemophilia. AB - Hemophilia A and B are X-linked monogenic disorders caused by deficiencies in coagulation factor VIII (FVIII) and factor IX (FIX), respectively. Current treatment for hemophilia involves intravenous infusion of clotting factor concentrates. However, this does not constitute a cure, and the development of gene-based therapies for hemophilia to achieve prolonged high level expression of clotting factors to correct the bleeding diathesis are warranted. Different types of viral and nonviral gene delivery systems and a wide range of different target cells, including hepatocytes, skeletal muscle cells, hematopoietic stem cells (HSCs), and endothelial cells, have been explored for hemophilia gene therapy. Adeno-associated virus (AAV)-based and lentiviral vectors are among the most promising vectors for hemophilia gene therapy. Stable correction of the bleeding phenotypes in hemophilia A and B was achieved in murine and canine models, and these promising preclinical studies prompted clinical trials in patients suffering from severe hemophilia. These studies recently resulted in the first demonstration that long-term expression of therapeutic FIX levels could be achieved in patients undergoing gene therapy. Despite this progress, there are still a number of hurdles that need to be overcome. In particular, the FIX levels obtained were insufficient to prevent bleeding induced by trauma or injury. Moreover, the gene-modified cells in these patients can become potential targets for immune destruction by effector T cells, specific for the AAV vector antigens. Consequently, more efficacious approaches are needed to achieve full hemostatic correction and to ultimately establish a cure for hemophilia A and B. PMID- 22671035 TI - Delayed ignition of autocatalytic combustion precursors: low-temperature nanomaterial binder approach to electronically functional oxide films. AB - Delayed ignition of combustion synthesis precursors can significantly lower metal oxide film formation temperatures. From bulk In(2)O(3) precursor analysis, it is shown here that ignition temperatures can be lowered by as much as 150 degrees C. Thus, heat generation from ~60 nm thick In(2)O(3) films is sufficient to form crystalline In(2)O(3) films at 150 degrees C. Furthermore, we show that the low processing temperatures of sufficiently thick combustion precursor films can be applied to the synthesis of metal oxide nanocomposite films from nanomaterials overcoated/impregnated with the appropriate combustion precursor. The resulting, electrically well-connected nanocomposites exhibit significant enhancements in charge-transport properties vs conventionally processed oxide films while maintaining desirable intrinsic electronic properties. For example, while ZnO nanorod-based thin-film transistors exhibit an electron mobility of 10(-3)-10(-2) cm(2) V(-1) s(-1), encasing these nanorods within a ZnO combustion precursor derived matrix enhances the electron mobility to 0.2 cm(2) V(-1) s(-1). Using commercially available ITO nanoparticles, the intrinsically high carrier concentration is preserved during nanocomposite film synthesis, and an ITO nanocomposite film processed at 150 degrees C exhibits a conductivity of ~10 S cm(-1) without post-reductive processing. PMID- 22671034 TI - Arginine-facilitated isomerization: radical-induced dissociation of aliphatic radical cationic glycylarginyl(iso)leucine tripeptides. AB - The gas phase fragmentations of aliphatic radical cationic glycylglycyl(iso)leucine tripeptides ([G(*)G(L/I)](+)), with well-defined initial locations of the radical centers at their N-terminal alpha-carbon atoms, are significantly different from those of their basic glycylarginyl(iso)leucine ([G(*)R(L/I)](+)) counterparts; the former lead predominantly to [b(2) - H](*+) fragment ions, whereas the latter result in the formation of characteristic product ions via the losses of (*)CH(CH(3))(2) from [G(*)RL](+) and (*)CH(2)CH(3) from [G(*)RI](+) through C(beta)-C(gamma) side-chain cleavages of the (iso)leucine residues, making these two peptides distinguishable. The alpha carbon-centered radical at the leucine residue is the key intermediate that triggers the subsequent C(beta)-C(gamma) bond cleavage, as supported by the absence of (*)CH(CH(3))(2) loss from the collision-induced dissociation of [G(*)RL(alpha-Me)](+), a radical cation for which the alpha-hydrogen atom of the leucine residue had been substituted by a methyl group. Density functional theory calculations at the B3LYP 6-31++G(d,p) level of theory supported the notion that the highly basic arginine residue could not only increase the energy barriers against charge-induced dissociation pathways but also decrease the energy barriers against hydrogen atom transfers in the GR(L/I) radical cations by ~10 kcal mol(-1), thereby allowing the intermediate precursors containing alpha- and gamma-carbon-centered radicals at the (iso)leucine residues to be formed more readily prior to promoting subsequent C(beta)-C(gamma) and C(alpha)-C(beta) bond cleavages. The hydrogen atom transfer barriers for the alpha- and gamma-carbon centered GR(L/I) radical cations (roughly in the range 29-34 kcal mol(-1)) are comparable with those of the competitive side-chain cleavage processes. The transition structures for the elimination of (*)CH(CH(3))(2) and (*)CH(2)CH(3) from the (iso)leucine side chains possess similar structures, but slightly different dissociation barriers of 31.9 and 34.0 kcal mol(-1), respectively; the energy barriers for the elimination of the alkenes CH(2)?CH(CH(3))(2) and CH(3)CH?CHCH(3) through C(alpha)-C(beta) bond cleavages of gamma-carbon-centered radicals at the (iso)leucine side chains are 29.1 and 32.8 kcal mol(-1), respectively. PMID- 22671037 TI - Identification of core functioning features for assessment and intervention in Autism Spectrum Disorders. AB - PURPOSE: Framed within a biopsychosocial approach, this study aimed to identify the main functionality dimensions that experts in the field of child development and child psychopathology considered as essential in the assessment-intervention process with young children with Autism Spectrum Disorders (ASD), using the International Classification of Functionality, Disability and Health for Children and Youth. METHOD: The Delphi method was used to obtain consensus among experts regarding the essential functionality features for the rehabilitation of young children with ASD. Therefore, web-based three-round survey was developed. RESULTS: There are more functionality features identified as more essential for the age group 3-6 than from the group birth-2 years of age. 49.4% of activities and participation dimensions were regarded as essential by experts, while only 13.9% of body functions were selected. 39.9% of environmental factors were also marked by experts as essential. CONCLUSIONS: Pervasive Developmental Disorders (PDD) are classified in diagnostic manuals-DSM-IV-TR and ICD-10. These classifications are valuable to detect signs/symptoms of health conditions; however, they are often not sufficient to develop individualized interventions. More functional information is needed to complement diagnostic data. The identified functionality dimensions of the ICF-CY complement diagnosis by differentiating relevant functioning aspects in all life domains, according to the biopsychosocial model and should always be addressed in the process of rehabilitation of young children with ASD. PMID- 22671038 TI - Autopsy case of delayed anaphylactic shock due to contrast medium. AB - We report an autopsy case of delayed anaphylactic shock due to contrast medium. A 17-year-old Japanese man underwent angiography using non-ionic contrast medium under the suspected diagnosis of Buerger's disease. Initial symptoms appeared 6 h after the administration of the contrast medium, and death was confirmed 11 h later. Considering the clinical course and the results of the autopsy, we concluded that the direct cause of the patient's death was severe acute circulatory failure due to a delayed allergic reaction to the contrast medium. The reported incidence of serious delayed reactions or biphasic reactions to non ionic contrast medium is extremely low; however, we should be aware of such rare adverse reactions. PMID- 22671039 TI - Compound heterozygosity of HLA-DRB3*01:01 and HLA-DRB4*01:01 as a potential predictor of fetal neonatal alloimmune thrombocytopenia. AB - BACKGROUND: Fetal neonatal alloimmune thrombocytopenia (FNAIT) is a life threatening bleeding disorder in the fetus or neonate caused by maternal alloantibodies directed against fetal platelet (PLT) antigens inherited from the father. The immune-dominant antigen leading to severe FNAIT is the human PLT antigen (HPA)-1, whose polymorphism constitutes an epitope for human leukocyte antigens (HLAs), usually DRB3*0101 leading to an immune response. STUDY DESIGN AND METHODS: In this study our aims were to find whether other allele variants of the beta subunit of the HLA-DR family specifically focused on the HLA residues that bind Position 33 of the HPA-1 integrin contribute to FNAIT development and affect response to treatment and whether coexistence of both anti-HPA-1a and anti HLA class I specific against the father's antigens leads to a more severe thrombocytopenia in the newborn. We examine the genotype of 23 mothers to newborns with FNAIT compared to a control group. RESULTS: Our results suggested that, when HPA-1 incompatibility with the husband is found, the presence of two HLA alleles (DRB3*01:01 and DRB4*01:01) in the mother increases the risk and severity of FNAIT and reduces the success of a preventive immunoglobulin G treatment. We provide a structural model for the molecular basis of the rational effects of the different HLA alleles. In addition, we found that the presence of both anti-HPA-1 and anti-HLAs did not aggravate FNAIT in comparison to mothers harboring only anti-HPA-1. CONCLUSION: Overall, we suggest that a specific genotyping of the mother in relation to HLA-DRB as well as HPA-1 can serve as an antenatal diagnostic tool, particularly in siblings of women who gave birth to neonates with FNAIT. PMID- 22671130 TI - Mitochondrial free [Ca(2+)] dynamics measured with a novel low-Ca(2+) affinity aequorin probe. AB - Mitochondria have a very large capacity to accumulate Ca(2+) during cell stimulation driven by the mitochondrial membrane potential. Under these conditions, [Ca(2+)](M) (mitochondrial [Ca(2+)]) may well reach millimolar levels in a few seconds. Measuring the dynamics of [Ca(2+)](M) during prolonged stimulation has been previously precluded by the high Ca(2+) affinity of the probes available. We have now developed a mitochondrially targeted double-mutated form of the photoprotein aequorin which is able to measure [Ca(2+)] in the millimolar range for long periods of time without problems derived from aequorin consumption. We show in the present study that addition of Ca(2+) to permeabilized HeLa cells triggers an increase in [Ca(2+)](M) up to an steady state of approximately 2-3 mM in the absence of phosphate and 0.5-1 mM in the presence of phosphate, suggesting buffering or precipitation of calcium phosphate when the free [Ca(2+)] reaches 0.5-1 mM. Mitochondrial pH acidification partially re-dissolved these complexes. These millimolar [Ca(2+)](M) levels were stable for long periods of time provided the mitochondrial membrane potential was not collapsed. Silencing of the mitochondrial Ca(2+) uniporter largely reduced the rate of [Ca(2+)](M) increase, but the final steady-state [Ca(2+)](M) reached was similar. In intact cells, the new probe allows monitoring of agonist-induced increases of [Ca(2+)](M) without problems derived from aequorin consumption. PMID- 22671131 TI - Predictive representation of other people's actions in joint action planning: an EEG study. AB - It has been postulated that when people engage in joint actions they form internal representations not only of their part of the joint task but of their co actors' parts of the task as well. However, empirical evidence for this claim is scarce. By means of high-density electroencephalography, this study investigated whether one represents and simulates the action of an interaction partner when planning to perform a joint action. The results showed that joint action planning compared with individual action planning resulted in amplitude modulations of the frontal P3a and parietal P3b event-related potentials, which are associated with stimulus classification, updating of representations, and decision-making. Moreover, there was evidence for anticipatory motor simulation of the partner's action in the amplitude and peak latency of the late, motor part of the Contingent Negative Variation, which was correlated with joint action performance. Our results provide evidence that when people engage in joint tasks, they represent in advance each other's actions in order to facilitate coordination. PMID- 22671132 TI - Toward a small molecule, biomimetic carbonic anhydrase model: theoretical and experimental investigations of a panel of zinc(II) aza-macrocyclic catalysts. AB - A panel of five zinc-chelated aza-macrocycle ligands and their ability to catalyze the hydration of carbon dioxide to bicarbonate, H(2)O + CO(2) -> H(+) + HCO(3)(-), was investigated using quantum-mechanical methods and stopped-flow experiments. The key intermediates in the reaction coordinate were optimized using the M06-2X density functional with aug-cc-pVTZ basis set. Activation energies for the first step in the catalytic cycle, nucleophilic CO(2) addition, were calculated from gas-phase optimized transition-state geometries. The computationally derived trend in activation energies was found to not correspond with the experimentally observed rates. However, activation energies for the second, bicarbonate release step, which were estimated using calculated bond dissociation energies, provided good agreement with the observed trend in rate constants. Thus, the joint theoretical and experimental results provide evidence that bicarbonate release, not CO(2) addition, may be the rate-limiting step in CO(2) hydration by zinc complexes of aza-macrocyclic ligands. pH-independent rate constants were found to increase with decreasing Lewis acidity of the ligand-Zn complex, and the trend in rate constants was correlated with molecular properties of the ligands. It is suggested that tuning catalytic efficiency through the first coordination shell of Zn(2+) ligands is predominantly a balance between increasing charge-donating character of the ligand and maintaining the catalytically relevant pK(a) below the operating pH. PMID- 22671133 TI - Total synthesis of (-)-polycavernoside A: Suzuki-Miyaura coupling approach. AB - A total synthesis of (-)-polycavernoside A, a marine lethal toxin isolated from the edible alga Gracilaria edulis , has been achieved via a convergent approach. The synthesis is highlighted by catalytic asymmetric syntheses of the two key fragments and their union through Suzuki-Miyaura coupling and Keck macrolactonization. PMID- 22671134 TI - Control in childbirth: a concept analysis and synthesis. AB - AIM: To report a concept analysis of control in childbirth. BACKGROUND: Control has a variety of definitions from a wide range of disciplines. In childbirth, however, the concept is more tenuous and depends on the context. It can be viewed in relationship to a woman's body and labour progression, pain, environment and the ability to request her method of birth. DATA SOURCES: Medline, CINAHL and PsycINFO databases were searched between 1970-2011 using the keywords, 'control', 'childbirth', 'labour' and 'delivery'. REVIEW METHODS: Walker and Avant's method of concept analysis was used for this review. In addition, cases were placed before defining attributes as recommended by Risjord. RESULTS: Four attributes of control were identified: decision-making, access to information, personal security and physical functioning. Antecedents include pregnancy and expectations of the birth. Consequences include childbirth satisfaction, childbirth experience, emotional well-being, fulfilment and the transition into motherhood. A model case, contrary case and borderline case are described. CONCLUSION: Clarifying the definition of control in childbirth and defining its attributes can help inform women and maternity providers throughout the world. This analysis provides clarity to a previously tenuous concept and allows practitioners to better understand the critical relationship between control in childbirth and satisfaction with the childbirth experience. It also has the potential to affect perinatal outcomes and subsequently healthcare costs. PMID- 22671135 TI - Clinical characteristics and risks of large congenital melanocytic naevi: a review of 31 patients at the Sydney Children's Hospital. AB - Large congenital melanocytic naevi (LCMN) are associated with an increased risk of malignancy and neurocutaneous melanocytosis (NCM). This Australian study aims to assess both the clinical characteristics of LCMN and the risks associated with it. The authors reviewed medical records of the Sydney Children's Hospital Dermatology Outpatient Clinic for the past 10 years and identified 31 eligible patients. A total of 14 boys and 17 girls with a median age of 0.13 years were assessed; 18 lesions were on the trunk, five were on the head, five were on the lower limbs and three were on the upper limbs. In all 20 patients had satellite naevi (the median number of the satellite naevi was 7.5). The patients were followed up for a median duration of 12 months. Central nervous system magnetic resonance imaging was performed on 19 patients and two (6.5%) were found to have NCM. Biopsies were performed on five patients; one patient (3.2%) was found to have benign proliferative nodules of undifferentiated spindle cells but no patient (0%) was found to have a malignancy. The clinical characteristics for the two patients with NCM and the patient with benign proliferative nodules suggest that the risk of both NCM and benign proliferative nodules may be greater with an increased number of satellite naevi and with the LCMN being larger in size. PMID- 22671137 TI - Abstracts of the First Biennial Symposium on Regulatory T Cells and T Helper Cells. March 30, 2012. London, United Kingdom. PMID- 22671138 TI - S100b protein levels in subretinal fluid in rhegmatogenous retinal detachment. AB - PURPOSE: To investigate the relevance of the concentration of S100B in subretinal fluid (SRF) with the postoperative anatomical and functional success and proliferative vitreoretinopathy (PVR) formation parameters in rhegmatogenous retinal detachment (RRD). METHODS: Fifty-three patients (34 male, 19 female) were included in this prospective study. Study group consisted of 46 patients who had scleral buckling (SB) surgery with the diagnosis of RRD. Control group consisted of six patients who had pars plana vitrectomy (PPV) for either full-thickness macular hole or subluxated intraocular lens. SRFs were obtained during SB surgery. Study cases were divided into three groups, corresponding to the duration of retinal detachment (DRD). Clinical characteristics including best corrected visual acuity (BCVA), anatomical status at 6 months, the presence of postoperative PVR that resulted in recurrent detachment and any possible re operations were recorded. The concentration of S100B was quantified by using an enzyme immunoassay test kit. RESULTS: The concentration of S100B in SRF increased significantly after RRD. And, S100B levels were evidently elevated in concordance with DRD. There was no correlation between the concentration of SRF - S100B with preoperative or postoperative BCVA. Again, S100B levels were not related to the extent of RRD or postoperative PVR formation. CONCLUSION: Concentration of S100B in SRF is good marker of retinal stress and increases in concordance with DRD. However it would not help to predict the possible anatomical and functional success or postoperative PVR formation. PMID- 22671140 TI - Characterization, cDNA cloning and expression pattern of relaxin gene during embryogenesis of Danio rerio. AB - We report the identification, the cDNA cloning, the temporal and spatial expression pattern analysis of the rln gene in the zebrafish Danio rerio. The deduced Rln B and A domains show different evolutionary conservation. Rln B domain shows higher similarity when compared to zebrafish and human RLN3 B domain than human RLN1 and RLN2 B domain. Differently, the zebrafish Rln A domain shows relatively low amino acid sequence similarity when compared with the same sequences. The rln gene is transcribed both during embryogenesis and in adult organism, where higher transcript level has been particularly evidenced in the brain. Moreover, we provide the first description of rln spatial expression pattern during embryonic development. In particular, we show restricted transcript localization starting at the pharyngula stage in olfactory placode, branchial arch region, and in a cell cluster near to otic vesicle. In larval stage, new transcription territories have been detected in both neural and non neural regions. In particular, in the brain, rln expression has been revealed in telencephalic region around anterior commissure, in the preoptic area, and in restricted rombencephalic cell clusters. Expression of rln gene in extra-neural territories has been detected in the pancreatic and thyroid gland regions. Danio rerio rln expression pattern analysis reveals shared features with the mammalian RLN gene, particularly in the brain, where it might have a role in the neurophysiological processes. In addition, expression in the thyroid and pancreas region suggests a function as a paracrine and endocrine hormone. PMID- 22671139 TI - Lichen myco- and photobiont diversity and their relationships at the edge of life (McMurdo Dry Valleys, Antarctica). AB - Lichen-forming fungi are among the most diverse group of organisms in Antarctica. Being poikilohydric, lichens are able to cope with harsh environmental conditions that exclude other organisms like vascular plants. The McMurdo Dry Valleys (Victoria Land, Continental Antarctica) are a hyperarid cold desert where macroscopic life is reduced to a few lichens and bryophyte species. We investigated the diversity of lichen-forming fungi and their associated photobionts in three valleys (Garwood, Marshall, and Miers). Correct identification of lichen-forming fungi from extreme ecosystems is complicated by the presence of numerous sterile and extremely modified thalli. To overcome this problem, we used a combined approach for the identification of the species present in the area, the first involving identification by means of standard characters and the second, two DNA-based (ITS region) species delimitation methods (General Mixed Yule-Coalescent model and genetic distances). In addition, we also used ITS sequences for the identification of the photobionts associated with the mycobionts. We studied the relationships between both bionts and assessed the degree of selectivity and specificity found in those associations. We also looked for landscape level spatial patterns in these associations. The two DNA-based methods performed quite differently, but 27 species of lichen forming fungi and five putative species of photobionts were found in the studied area. Although there was a general trend for low selectivity in the relationships, high specificity was found in some associations and differential selectivity was observed in some lichen-forming fungi. No spatial structure was detected in the distribution of photobionts in the studied area. PMID- 22671141 TI - Development of psoriasis 10 years after allogeneic hematopoietic cell transplantation from non-psoriatic donor: Further evidences for genetics and immunopathogenesis of psoriasis. PMID- 22671142 TI - Topotactic reduction yielding black titanium oxide nanostructures as metallic electronic conductors. AB - Detailed analyses of reduced, single crystal, rutile-type TiO(2) via high resolution transmission electron microscopy (TEM) are reported which reveal that the reduction proceeds topotactically via interstitial diffusion of Ti ions at low temperature, around 350 degrees C. This important finding encouraged the production of various nanostructured reduced titanium oxides from TiO(2) precursors with morphology retention, and in the process, the synthesis of black titanium oxide nanorods using TiO(2) nanorods was demonstrated. Interestingly, as opposed to the semiconductive behavior of Ti(2)O(3) synthesized at high temperature, topotactically synthesized Ti(2)O(3) exhibits metallic electrical resistance, and the value at room temperature is quite low (<6 MUOmega m, comparable to graphite). These unique properties are probably due to the lattice strains generally observed for topotactically synthesized Ti(2)O(3). This work shows that topotactically reduced titanium oxides can have fascinating properties as well as nanostructures. PMID- 22671143 TI - Manganese porphyrin catalyzed cycloisomerization of enynes. AB - Cycloisomerization of 1,6-enynes to five- or six-membered ring systems is successfully carried out in the presence of a cationic manganese(III) catalyst. The use of a structurally rigid tetradentate porphyrin as the equatorial ligand and a weakly coordinating axial ligand is the key to bringing out the catalytic reactivity of manganese for the reaction. The axial ligand of the catalyst has a marked effect on the product and selectively aids the formation of five- or six membered cyclic products. PMID- 22671144 TI - Needle electromyography at 1 month predicts paralysis of elbow flexion at 3 months in obstetric brachial plexus lesions. AB - AIM: Treatment decisions in obstetric brachial plexus lesions are often based on clinical paralysis of elbow flexion at 3 months of age, when electromyography (EMG) is misleading because motor unit potentials (MUPs) occur in clinically paralytic muscles. We investigated whether EMG at 1 week or 1 month identifies infants with flexion paralysis at 3 months, allowing early referral. METHOD: Forty-eight infants (27 females, 21 males) were prospectively studied. The presence or absence of flexion paralysis at around 1 week (median 9 d; range 5 17d), 1 month (median 31 d; range 24-53 d), and 3 months of age (median 87 d; range 77-106 d) was noted for clinical (shoulder external rotation, elbow flexion, extension, and supination) and EMG parameters (denervation activity, MUPs and polyphasic MUPs in the deltoid, biceps, and triceps muscles). RESULTS: At 1 month, the absence of biceps MUPs had a sensitivity of 95% for later flexion paralysis, and absence of deltoid MUPs had a sensitivity of 100% for flexion paralysis; the false-positive rates for the same findings were 21% and 33% respectively. EMG at 3 months was highly misleading as MUPs were seen in 19 of 20 clinically paralytic biceps muscles. INTERPRETATION: EMG at 1 month can identify severe cases of flexion paralysis for early referral EMG of the biceps at 3 months is highly misleading; the discrepancy between the EMG and clinical testing may be due to abnormal axonal branching and aberrant central motor control. PMID- 22671146 TI - Extramammary Paget's disease of the vulva: An annotated review of the current literature. AB - Extramammary Paget's disease is a rare and unusual neoplastic entity that presents mainly on apocrine gland-bearing skin. The vulva is the most common site of involvement but any area of the anogenital skin can be affected. Due to its rarity, variable clinical course and deceptive histological appearance it has a high misdiagnosis rate and both gynaecologists and dermatologists have limited experience in its management. The significance of the disease lies in its association with underlying malignancy as well as its inherent ability to invade the dermis and metastasise. The management is notoriously complicated and recurrence rates are high despite aggressive surgeries. Several alternative modalities are being explored, with results that are often variable and unpredictable. This review summarises the histopathological, clinical and therapeutic features of extramammary Paget's disease of the vulva reported in recent years. PMID- 22671247 TI - 'A very dangerous conversation': the patient's internal conflicts elaborated through the use of ethnic and religious differences between analyst and patient. PMID- 22671145 TI - Transcriptional networks driving enhancer function in the CFTR gene. AB - A critical cis-regulatory element for the CFTR (cystic fibrosis transmembrane conductance regulator) gene is located in intron 11, 100 kb distal to the promoter, with which it interacts. This sequence contains an intestine-selective enhancer and associates with enhancer signature proteins, such as p300, in addition to tissue-specific TFs (transcription factors). In the present study we identify critical TFs that are recruited to this element and demonstrate their importance in regulating CFTR expression. In vitro DNase I footprinting and EMSAs (electrophoretic mobility-shift assays) identified four cell-type-selective regions that bound TFs in vitro. ChIP (chromatin immunoprecipitation) identified FOXA1/A2 (forkhead box A1/A2), HNF1 (hepatocyte nuclear factor 1) and CDX2 (caudal-type homeobox 2) as in vivo trans-interacting factors. Mutation of their binding sites in the intron 11 core compromised its enhancer activity when measured by reporter gene assay. Moreover, siRNA (small interfering RNA)-mediated knockdown of CDX2 caused a significant reduction in endogenous CFTR transcription in intestinal cells, suggesting that this factor is critical for the maintenance of high levels of CFTR expression in these cells. The ChIP data also demonstrate that these TFs interact with multiple cis-regulatory elements across the CFTR locus, implicating a more global role in intestinal expression of the gene. PMID- 22671248 TI - A commentary on 'A very dangerous conversation' by Aisha Abbasi. PMID- 22671249 TI - A review of 'A very dangerous conversation' by Aisha Abbasi. PMID- 22671250 TI - Current developments in the practice of individual psychoanalytic psychodrama in France. AB - The authors present the history of individual psychoanalytic psychodrama and its current developments as practised in France. They put forward the technique, objectives and rules, along with the indications, limits and risks that ensue from the specific nature of this therapeutic approach. Through its technical adjustments, individual psychoanalytic psychodrama provides a therapeutic option that is appropriate to the defences prevalent in many patients that cause classical psychotherapies to fail: massive inhibition, operative functioning far removed from affects or in false self mode; phobias, disavowal or splitting of the internal psychic life and emotions; prevalence of short discharge circuits in acted-out behaviours and bodily or visceral complaints and expressions. Psychodrama utilizes these defences not in order to eliminate them but to 'subvert' them so that they can continue to carry out their protective role, in particular ensuring narcissistic continuity. At the same time, psychodrama relaxes these defences and facilitates a possible filtering through of the repressed material. Through the number of actors and the diffraction of transference that this allows, psychodrama provides a possibility of adjusting the potentially traumatic effect of the encounter with the object and the instigation of the transference in the regressive dimension induced by any psychotherapeutic process. PMID- 22671251 TI - The unreachable object? Difficulties and paradoxes in the analytical relationship with borderline patients. AB - The author investigates the main difficulties the analyst encounters in borderline patient analysis, focusing on the specific way in which such patients put the analyst's mental functioning to the test and highlighting the most salient elements of the transference-countertransference dynamic. The author picks out several of the paradoxes that characterize the analytical relationship with these patients, who are constantly seeking contact with the object, which is inevitably traumatic for them. On the basis of highly detailed clinical material, the author demonstrates how - no matter which theoretical-clinical model is adopted - a specific technical problem with these patients is how to manage their intense destructiveness. With these patients, countertransferential difficulties are inevitably predominant because of the looming threat of the destruction of the analytical relationship. Maintaining a balance between the recognition legitimization of primary narcissistic mirroring needs and the recognition control of narcissistic demands and attacks on the analytical link is as crucial as it is complex. The paper examines the most important therapeutic and anti therapeutic factors, highlighting the importance of countertransference analysis and self-analysis as ways of accessing as yet unrepresented elements of the patient and analyst respectively. Particular attention is given to the role played by the analyst's subjectivity and to the enactment. PMID- 22671252 TI - The colourless canvas: representation, therapeutic action and the creation of mind. AB - Freud's initial formulations viewed psychoanalysis as working towards the rediscovery of psychic elements - thoughts, feelings, memories, wishes, etc. - that were once known - represented in the mind, articulatable, thinkable - but then disguised and/or barred from consciousness. His subsequent revisions implicated a second, more extensive category of inchoate forces that either lost or never attained psychic representation and, although motivationally active, were not fixed in meaning, symbolically embodied, attached to associational chains, etc. Following Freud's theory of representation, the author conceptualizes these latter forces as "unrepresented" or "weakly represented" mental states that make a demand upon the mind for work and require transformation into something that is represented in the psyche, if they are to be thought about or used to think with. This paper describes, discusses and presents illustrations of this transformational process (figurability),that moves intersubjectively from unrepresented or weakly represented mental states to represented mental states, from force to meaning, from the inchoate to mental order. PMID- 22671253 TI - Has infantile sexuality anything to do with infants? AB - Classical psychoanalytic theory draws many concepts from mental processes that are assumed to arise in the infant and influence the adult mind. Still, psychoanalytic practice with mothers and infants has been integrated but little within general psychoanalytic theory. One reason is that only few analysts have utilized such practice to further theory. Another reason is that infant therapists tend to abandon classical psychoanalytic concepts in favour of attachment concepts. As a result the concept of infantile sexuality, so central to classical theory, plays an unobtrusive role in clinical discussions on infant therapy. The author argues that infantile sexuality plays an important role in many mother-infant disturbances. To function as a clinical concept, it needs to be delineated from attachment and be understood in the context of mother-infant interaction. Two examples are provided; one where the analyst's infantile sexuality emerged in a comment to the infant. Another is a case of breast-feeding problems with a little boy fretting at the breast. This is interpreted as reflecting the mother's infantile sexual conflicts as well as the boy's emerging internalization of them. Thus, to conceptualize such disorders we need to take into account the infantile sexuality in both mother and baby. PMID- 22671254 TI - Reflections on psychoanalytic technique with adolescents today: pseudo pseudomaturity. AB - The starting point for this paper is current observation of adolescents who seem unable to break the latency structure, making it difficult for the adolescence process to become established. These youngsters present with a specific set of characteristics which the author proposes to call 'pseudo-pseudomaturity': they seem for the most part well adapted, with an absence of unconscious conflicts. However, they differ from Meltzer's description of pseudomaturity in that the omnipotent attitude of dependence-denying is not seen. On the contrary, they seem eager to take the opportunity to have the infantile true self accepted and contained before they can safely enter the process of adolescence, with all its turbulence. Some aspects of our culture are discussed in relation to the psychic configuration described. Using fragments from the analysis of a 19 year-old patient, the paper looks at technical issues raised by these cases. There is an emphasis on the analyst's own mental processes and the importance of being able to contain the emotional turbulence that cannot be sensed by the patient. The author sets out the different modalities suggested/tested/proposed in the analytic relationship in support of the transferential work. Some questions regarding how and when to make interpretations are also discussed. In these types of cases, the psychoanalytic process carries a two-fold responsibility - to the patient and to society as a whole, in view of the creative potential that adolescents represent, essential for social change and growth. PMID- 22671255 TI - Delusional development in child autism at the onset of puberty: vicissitudes of psychic dimensionality between disintegration and development. AB - Although the psychogenetic hypotheses on child autism have been superseded, psychoanalysis can still reflect on the relational exchange and its sensory aspects in concomitance with the mental development of these patients. Without making generalizations as regards the pathogenesis, but considering the specific features of each autistic child, it may be possible to achieve an integration of those islands of competence that make up these patients' limited personal heritage. Such integration may be reached through the analysis of representational, emotional and relational transformations. The first part of this article describes the case of an autistic child in treatment from the age of four on a four-times-weekly basis who, during puberty, developed severe formal thought disorders together with delusional and hallucinatory formations. The second part develops some post-Jungian theoretical contributions, such as the concept of self as nothingness and the idea of the unsaturated archetype, so as to evaluate the function of some a-priori concepts in support of the analyst's position. These concepts are considered in relation to Bion's model of transformation, and to the formulations on dimensional awareness, especially on the shift from a two-dimensionality to three-dimensionality view, as well as to the rhythm of the object's presence and absence. PMID- 22671256 TI - Sigmund Freud and Otto Rank: debates and confrontations about anxiety and birth. AB - The publication of Otto Rank's The Trauma of Birth (1924) gave rise to an intense debate within the secret Committee and confronted Freud with one of his most beloved disciples. After analyzing the letters that the Professor exchanged with his closest collaborators and reviewing the works he published during this period, it is clear that anxiety was a crucial element among the topics in dispute. His reflections linked to the signal anxiety concept allowed Freud to refute Rank's thesis that defined birth trauma as the paradigmatic key to understanding neurosis, and, in turn, was a way of confirming the validity of the concepts of Oedipus complex, repression and castration in the conceptualization of anxiety. The reasons for the modifications of anxiety theory in the mid-1920s cannot be reduced, as Freud would affirm officially in his work of 1926, to the detection of internal contradictions in his theory or to the desire to establish a metapsychological version of the problem, for they gain their essential impulse from the debate with Rank. PMID- 22671257 TI - John Cage and W. R. Bion: an exercise in interdisciplinary dialogue. AB - The author discusses some striking convergences which appear in the thought of two unsettling and powerfully stimulating personalities of the 20th century: John Cage in music and art, and W.R. Bion in psychoanalysis. Both foster openness to the unknown and the need to tolerate 'uncertainties, mysteries, doubts', arguing for an attitude requiring negative valence and receptive emptiness. In their search for fresh personal awareness of reality aimed at allowing mental transformation and growth, both strive to disturb intellectual comfort and do not hesitate to use pro(e)vocative and even shocking means. They both propose an attitude towards tradition which demands the freedom to use and recreate inherited knowledge in a personal and innovative way. Finally, both Cage and Bion maintained a highly auto-reflective attitude, carefully considering the artist's/psychoanalyst's contribution to the process of art and psychoanalysis. These convergences probably represent important and wider contemporary cultural trends which permeate in their different realizations. PMID- 22671258 TI - Opening plenary. PMID- 22671259 TI - Dreams. PMID- 22671260 TI - Sexuality panel. PMID- 22671261 TI - History of psychoanalysis in Mexico. PMID- 22671262 TI - Impact and influence of relational psychoanalysis. PMID- 22671263 TI - Kleinian theory. PMID- 22671264 TI - Field theory. PMID- 22671265 TI - Psychoanalysis, sociology and European Jewish culture. PMID- 22671266 TI - New methods for integrating divergent concepts (Parts 1 & 2). PMID- 22671267 TI - Project committee on clinical observation panels. PMID- 22671268 TI - Recent contributions from clinical research: on mental processing, on dreams and dreaming, and on the role of phantasies about parental couple relationships. PMID- 22671269 TI - 'Consenting to be robbed so as not to be murdered': psychoanalytic treatments of chronically depressed patients in two parallel depression research studies. PMID- 22671270 TI - La sexualidad en el analisis: Escucha y enactment [sexuality in analysis: analytic listening and enactment]. PMID- 22671271 TI - Disruptions and working through in the supervisory process. PMID- 22671272 TI - Impasse revisited. PMID- 22671273 TI - Experience in the treatment of sexual difficulties: strengths and limitations of the psychoanalytic approach. PMID- 22671274 TI - The closing plenary. PMID- 22671277 TI - Isidoro Berenstein (1932-2011). PMID- 22671279 TI - Ultrafast conformational dynamics of pyranine during excited state proton transfer in aqueous solution revealed by femtosecond stimulated Raman spectroscopy. AB - Proton transfer reaction plays an essential role in a myriad of chemical and biological processes, and to reveal the choreography of the proton motion intra- and intermolecularly, a spectroscopic technique capable of capturing molecular structural snapshots on the intrinsic time scale of proton transfer motions is needed. The photoacid pyranine (8-hydroxypyrene-1,3,6-trisulfonic acid, HPTS) serves as a paradigm case to dissect excited state proton transfer (ESPT) events in aqueous solution, triggered precisely by photoexcitation. We have used femtosecond stimulated Raman spectroscopy (FSRS) to yield novel insights into the ultrafast conformational dynamics of photoexcited HPTS in complex with water and acetate molecules. Marker bands attributed to the deprotonated form of HPTS (1139 cm(-1), ~220 fs rise) appear earlier and faster than the monomer acetic acid peak (864 cm(-1), ~530 fs rise), indicating that water molecules actively participate in the ESPT chain. Several key low-frequency modes at 106, 150, 195, and 321 cm( 1) have been identified to facilitate ESPT at different stages from 300 fs, 1 ps, to 6 ps and beyond, having distinctive dynamics contributing through hydrogen bonds with 0, 1, and more intervening water molecules. The time-resolved FSRS spectroscopy renders a direct approach to observe the reactive coupling between the vibrational degrees of freedom of photoexcited HPTS in action, therefore revealing the anharmonicity matrix both within HPTS and between HPTS and the neighboring acceptor molecules. The observed excited state conformational dynamics are along the ESPT multidimensional reaction coordinate and are responsible for the photoacidity of HPTS in aqueous solution. PMID- 22671278 TI - A randomized controlled trial evaluating recovery and survival of 6% dimethyl sulfoxide-frozen autologous platelets in healthy volunteers. AB - BACKGROUND: Availability of platelets (PLTs) is severely limited by shelf life in some settings. Our objective was to determine and compare to Food and Drug Administration (FDA) criteria the PLT recovery and survival of autologous PLTs cryopreserved at -65 degrees C or less in 6% dimethyl sulfoxide (DMSO) reconstituted with a no-wash method (cryopreserved PLTs [CPPs]) compared to autologous fresh PLTs. STUDY DESIGN AND METHODS: This was a randomized, Phase I study analyzing PLT viability and in vitro function in consenting healthy subjects. Apheresis PLTs (APs) were collected in plasma. APs were suspended in 6% DMSO, concentrated, and placed at not more than -65 degrees C for 7 to 13 days. Frozen CPPs were thawed at 37 degrees C and resuspended into 25 mL of 0.9% NaCl. Control PLTs (fresh autologous) and CPPs were labeled with (111) In or (51) Cr, and recovery and survival after reinfusion were determined using standard methods. A panel of in vitro assays was completed on APs and CPPs. RESULTS: After frozen storage, CPPs retained 82% of AP yield and showed increased PLT associated P-selectin and reduced responses to agonists. CPP 24-hour recovery (41.6 +/- 9.7%) was lower than for fresh PLTs (68.4 +/- 8.2%; p < 0.0001) and did not meet the current FDA criterion. CPPs had diminished survival compared to fresh PLTs (7.0 +/- 2.1 days vs. 8.4 +/- 1.2 days, respectively; p = 0.018), but did meet and exceed the FDA criterion for survival. CONCLUSION: While 24-hour recovery does not meet FDA criteria for liquid-stored PLTs, the CPP survival of circulating PLTs was surprisingly high and exceeded the FDA criteria. These data support proceeding with additional studies to evaluate the clinical effectiveness of CPPs. PMID- 22671280 TI - Copper benzene tricarboxylate metal-organic framework with wide permanent mesopores stabilized by Keggin polyoxometallate ions. AB - Porous solids with organized multiple porosity are of scientific and technological importance for broadening the application range from traditional areas of catalysis and adsorption/separation to drug release and biomedical imaging. Synthesis of crystalline porous materials offering a network of uniform micro- and mesopores remains a major scientific challenge. One strategy is based on variation of synthesis parameters of microporous networks, such as, for example, zeolites or metal-organic frameworks (MOFs). Here, we show the rational development of an hierarchical variant of the microporous cubic Cu(3)(BTC)(2) (BTC = 1,3,5-benzenetricarboxylate) HKUST-1 MOF having strictly repetitive 5 nm wide mesopores separated by uniform microporous walls in a single crystal structure. This new material coined COK-15 (COK = Centrum voor Oppervlaktechemie en Katalyse) was synthesized via a dual-templating approach. Stability was enhanced by Keggin type phosphotungstate (HPW) systematically occluded in the cavities constituting the walls between the mesopores. PMID- 22671281 TI - NGAL excretion is higher from the healthy side than from the injured side in unilateral acute kidney injury. PMID- 22671282 TI - Sterilization of bone allografts by microwave and gamma radiation. AB - PURPOSE: Bone allografts are used to enhance healing in osteotomies, arthrodesis, fractures and to replace bone loss resulting from tumour or trauma. However, a major concern associated with the bone allografts is the potential for disease transmission. Various sterilization techniques have been developed to prevent infection through allografts. This study was undertaken with the aim of exploring the use of microwave radiation for sterilization of bone allografts and to compare with gamma radiation sterilization. MATERIALS AND METHODS: Bone allografts were processed from femoral heads obtained from living donors. The effect of microwave and gamma radiation on the bacteria isolated from bone allograft was evaluated. The microwave radiation treatment was performed at 2450 MHz (frequency) for varying lengths of time at maximum power 900 Watts (W). Viability of three Gram-positive bacteria - Bacillus subtilis, Corynebacterium, Staphylococcus aureus and three Gram-negative bacteria - Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa was examined after irradiation of bacterial suspensions and contaminated processed bone allografts. The sterility test of microwave and gamma irradiated bone allograft was carried out in accordance with ISO (International Organization for Standardization) 11737-2. RESULTS: Microwave irradiation (2450 MHz and 900 W) of bacterial isolates resulted in complete inactivation within 60 seconds. The contaminated bone samples showed no growth of organisms after 2 minutes of exposure to microwave irradiation. No viable counts were detected in bone grafts inoculated with Gram negative bacterial species on gamma irradiation to a dose of 15 kGy. Bones contaminated with Gram-positive bacteria required a higher dose of 20 kGy for complete inactivation. CONCLUSIONS: The study shows that sterilization of contaminated femoral head bone allografts can be achieved by short exposure of 2 min to 2450 MHz and 900 W microwave radiation. PMID- 22671283 TI - An immunohistochemical study of the oviduct in the domestic fowl (Gallus domesticus). AB - This study describes the distribution of vimentin, desmin, smooth muscle actin (SMA) and laminin in the oviduct of the laying domestic fowl. Vimentin immunostaining was localised in the luminal epithelium of the infundibulum, magnum, magnum-isthmus junction and isthmus. The luminal epithelium of the shell gland regions displayed weak vimentin immunostaining. Vimentin immunostaining was demonstrated in the glandular grooves of the tubular infundibular region. In contrast, gland cells in the magnum, isthmus and shell gland regions were vimentin immunonegative. Fibroblasts and vascular endothelial cells in the lamina propria of the oviductal regions studied exhibited vimentin immunostaining. Strong desmin and SMA immunostaining were present in the smooth muscle cells of the tunica muscularis and vascular tunica media. In this study, basement membranes underlying the luminal and glandular epithelia were immunopositive for laminin. In addition, basement membranes associated with smooth muscle cells exhibited laminin immunostaining. The results of the study indicate that the immunolocalisation of desmin, SMA and laminin in the oviduct of the domestic fowl is similar to that in the mammalian uterus. The immunolocalisation of vimentin in the domestic fowl varies depending on the oviductal region. PMID- 22671284 TI - Veterinary laboratory quality management--it takes a village. PMID- 22671285 TI - Flames, rings, veils, and eggs... the many faces of cytoplasm. PMID- 22671286 TI - Comparison of manual polychromatophilic cell and automated reticulocyte quantification in evaluating regenerative response in anemic dogs. AB - BACKGROUND: Degree of polychromasia and reticulocyte counts are commonly used in veterinary medicine to evaluate response to anemia. The quantitative association between these 2 measurements has not been evaluated. OBJECTIVE: The aim of this retrospective study was to compare automated reticulocyte percents and counts with those of polychromatophilic cells on blood films from dogs. METHODS: Blood films and medical records from 30 clinically healthy dogs and 60 anemic dogs were evaluated. Manual percentage of polychromatophilic cells (MPP) was determined by counting cells in 10 1000* fields, and automated reticulocyte percentage (ARP) was measured using an ADVIA 120 hematology analyzer; absolute polychromatophilic cell and reticulocyte counts were then calculated. Degree of polychromasia, estimated as slight, mild, moderate, marked was documented. Percentages and absolute counts of polychromatophilic cells and reticulocytes were compared using least squares regression and Pearson's correlation coefficients. RESULTS: The reference interval for MPP in healthy dogs was 0.21-0.26%. Correlation between MPP and ARP was highest when all levels were considered (n = 60, r = .98, P < .0001), strong when ARP was > 5% (n = 20, r = .91, P < .0001), and poor when ARP was 1-2% (n = 20, r = .35, P < .0001). Results were similar for comparisons of absolute reticulocyte and polychromatophilic cell counts, with the best correlation found when all levels of counts were analyzed together (r = .96) and for automated reticulocyte counts > 150,000/MUL (r = .94). Correlation of estimates of polychromasia with ARP was good (r = .83). CONCLUSION: In anemic dogs MPP can be used for assessment of regeneration, especially in dogs with higher levels of ARP. Standard quantification of reticulocytes is more accurate in dogs with lesser degrees of regeneration. PMID- 22671287 TI - Mammary gland carcinoma in a dog with peripheral blood and bone marrow involvement associated with disseminated intravascular coagulation. AB - A 7-year-old female Leonberger dog was referred to the National Veterinary School of Lyon Teaching Hospital with a 2-day history of anorexia and bleeding. A mammary mass had been removed 7 months earlier, but histologic examination was not performed. On physical examination, the dog was depressed and had pale mucous membranes and numerous petechiae and hematomas. Significant laboratory findings were moderate thrombocytopenia, prolonged prothrombin, activated partial thromboplastin, and thrombin times, hypofibrinogenemia, and increased concentration of fibrin(ogen) degradation products. A peripheral blood smear, buffy coat preparation, and bone marrow aspirate contained low numbers of large atypical cells that had moderate nuclear:cytoplasmic ratios, oval nuclei with multiple prominent nuclei, and basophilic cytoplasm with villous projections. A small nodule was found in the left inguinal mammary gland, and a fine-needle aspirate contained cells similar to those in blood and bone marrow. In samples of blood, bone marrow, and the mammary mass, the neoplastic cells were immunoreactive for cytokeratin. The diagnosis was mammary carcinoma with secondary disseminated intravascular coagulation (DIC) and disseminated tumor cells in bone marrow and circulating tumor cells in blood; this diagnosis was not confirmed by histopathologic examination. Owing to clinical deterioration and the poor prognosis, the dog was euthanized and a necropsy was not performed. This is the first report of a canine mammary carcinoma with circulating tumor cells and secondary DIC. PMID- 22671288 TI - Implementation of ICF in goal setting in rehabilitation of children with chronic disabilities at Beitostolen Healthsports Centre. AB - PURPOSE: Develop an International Classification of Functioning, Disability and Health (ICF) Code Set, useful in goal oriented rehabilitation of a study population of children with chronic disabilities. METHOD: A triangulation of methods, using an interview to identify the main needs and goals of the study population, and a questionnaire to identify the main problems, with a registration of the frequency within each category. After qualitative and quantitative analyses this resulted in two sets of ICF categories. These two sets were then compared and merged into a proposed ICF Code Set for goal setting. RESULTS: Thirty categories were identified from the interviews and the following linking process. Problems were reported in all suggested categories within the ICF questionnaire, resulting in 49 categories. The comparison of the two sets of categories resulted in a proposed ICF Code Set of 40 categories. CONCLUSIONS: Through a triangulation of methods, we developed a tailored code set for the goal setting process in rehabilitation for children with a disability, taking into account both individual preferences and the health professionals' perspective. Although the external validity is limited, our methodological procedures may have relevance for the implementation of ICF in other clinical settings and populations. PMID- 22671289 TI - Roles of Mac-1 and glycoprotein IIb/IIIa integrins in leukocyte-platelet aggregate formation: stabilization by Mac-1 and inhibition by GpIIb/IIIa blockers. AB - Circulating platelet-leukocyte hetero-aggregates play an important role in acute cardiovascular events and hypersensitivity reactions. The association involves the receptor families of selectins and integrin. The objective of this study was to investigate the role of CD11b/CD18 integrin (Mac-1) in hetero-aggregate formation and search for a counter-receptor on platelets ready to interact with Mac-1. As a model of leukocytes, Mac-1 presenting Chinese hamster ovary (CHO) cells were used to evaluate the role of Mac-1 in hetero-aggregate formation. The amount of CHO cell-bound active and inactive platelets was measured by flow cytometry, while the counter-receptors on platelets were identified via using blocking antibodies. We observed significant platelet adhesion on Mac-1-bearing cells when platelet-rich plasma or activated platelets were present. Inactive platelets did not adhere to Mac-1-bearing cells. Addition of fibrinogen, a ligand of Mac-1 significantly increased platelet binding. CD40L was demonstrated to act similarly on Mac-1. Inhibition of platelet GpIIb/IIIa completely abolished CHO cell-platelet aggregation. In our study, we have shown for the first time that Mac-1 mediates the formation of hetero-aggregates without selectin tethering when Mac-1 ligands such as fibrinogen or CD40L are present and blockers of platelet GpIIb/IIIa are able to diminish this interaction. PMID- 22671290 TI - Microbial dynamics and flagellate grazing during transition to winter in Lakes Hoare and Bonney, Antarctica. AB - The planktonic microbial communities of Lakes Hoare and Bonney were investigated during transition into winter. We hypothesized that the onset of darkness induces changes in the functional role of autotrophic and heterotrophic microplankton. Bacteria decreased in Lake Hoare during March-April, while in Lake Bonney bacterial abundances varied. Heterotrophic nanoflagellates (HNAN), phototrophic nanoflagellates (PNAN) and ciliates showed no marked decline with the onset of winter. PNAN outnumbered HNAN in both lakes. Grazing rates of HNAN in Lake Hoare ranged up to 30.8 bacteria per cell day(-1). The HNAN community grazed between 3.74 and 36.6 ng of bacterial carbon day(-1). Mixotrophic PNAN had grazing rates up to 15.2 bacteria per cell day(-1), and their daily community grazing exceeded bacterial production. In Lake Bonney East, PNAN grazing rates ranged up to 12.48 bacteria per cell day(-1) and in Lake Bonney West up to 8.16 bacteria per cell day(-1). As in Lake Hoare, the mixotrophic PNAN grazing rates (up to 950 ng C day(-1)) usually exceeded bacterial production. HNAN grazing rates were generally similar to those in Lake Hoare. As winter encroaches, these lakes move progressively towards heterotrophy and probably function during the winter, enabling populations to enter the short austral summer with actively growing populations. PMID- 22671291 TI - Teaching young dogs new tricks: improving occupational therapists' referral prioritization capacity with a web-based decision-training aid. AB - OBJECTIVE: A web-based clinical decision aid was designed to improve novices' capacity to prioritize occupational therapy referrals in community mental health teams. The aim of this research was to test the effectiveness of the decision aid. DESIGN: A trial was conducted using a consensus expert policy as the educational intervention; a one-group pre-test, post-test design was chosen to measure any effect of training. PARTICIPANTS: A total of 100 pre-registration occupational therapy students accessed the decision aid; they prioritized a set of referrals before and after being trained with graphical and descriptive representations of the expert policy. SETTING: Data were collected online via the World Wide Web from students at 12 UK universities. RESULTS: The effect of training was demonstrated through more accurate prioritization ratings when matched with expert ratings on the same referrals and more accurate judgement policies when matched with the consensus standard judgement policy. CONCLUSION: The tool was found to be effective as it improved referral prioritization capacity. PMID- 22671292 TI - Interfacing nanocarbons with organic and inorganic semiconductors: from nanocrystals/quantum dots to extended tetrathiafulvalenes. AB - There is no doubt that the outstanding optical and electronic properties that low dimensional carbon-based nanomaterials exhibit call for their implementation into optoelectronic devices. However, to harvest the enormous potential of these nanocarbons it is essential to probe them in multifunctional electron donor acceptor systems, placing particular attention on the interactions between electron donors/electron acceptors and nanocarbons. This feature article outlines challenges and recent breakthroughs in the area of interfacing organic and inorganic semiconductors with low-dimensional nanocarbons that range from fullerenes (0D) and carbon nanotubes (1D) to graphene (2D). In the context of organic semiconductors, we focus on aromatic macrocycles and extended tetrathiafulvalenes, and CdTe nanocrystals/quantum dots represent the inorganic semiconductors. Particular emphasis is placed on designing and probing solar energy conversion nanohybrids. PMID- 22671293 TI - Real-time imaging of plasma membrane deformations reveals pre-fusion membrane curvature changes and a role for dynamin in the regulation of fusion pore expansion. AB - Assays for real-time investigation of exocytosis typically measure what is released from the granule. From this, inferences are made about the dynamics of membrane remodeling as fusion progresses from start to finish. We have recently undertaken a different approach to investigate the fusion process, by focusing not primarily on the granule, but rather its partner in exocytosis - the plasma membrane. We have been guided by the idea that biochemical interactions between the granule and plasma membranes before and during fusion, cause changes in membrane conformation. To enable study of membrane conformation, a novel imaging technique was developed combining polarized excitation of an oriented membrane probe 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (diI) with total internal reflection fluorescence microscopy (pTIRFM). Because this technique measures changes in membrane conformation (or deformations) directly, its usefulness persists even after granule cargo reporter (catecholamine, or protein), is no longer present. In this mini-review, we first summarize the workings of pTIRFM. We then discuss the application of the technique to investigate deformations in the membrane preceding fusion, and later, during fusion pore expansion. Finally, we discuss how expansion of the fusion pore may be regulated by the GTPase activity of dynamin. PMID- 22671294 TI - Homodimerization and isoform-specific heterodimerization of neuroligins. AB - Neuroligins are postsynaptic adhesion proteins involved in the establishment of functional synapses in the central nervous system. In rodents, four genes give rise to neuroligins that function at distinct synapses, with corresponding neurotransmitter and subtype specificities. In the present study, we examined the interactions between the different neuroligins by isolating endogenous oligomeric complexes using in situ cross-linking on primary neurons. Examining hippocampal, striatal, cerebellar and spinal cord cultures, we found that neuroligins form constitutive dimers, including homomers and, most notably, neuroligin 1/3 heteromers. Additionally, we found that neuroligin monomers are specifically retained in the secretory pathway through a cellular quality control mechanism that involves the neuroligin transmembrane domain, ensuring that dimerization occurs prior to cell surface trafficking. Lastly, we identified differences in the dimerization capacity of autism-associated neuroligin mutants, and found that neuroligin 3 R471C mutants can form heterodimers with neuroligin 1. The pervasive nature of neuroligin dimerization indicates that the unit of neuroligin function is the dimer, and raises intriguing possibilities of distinct heterodimer functions, and of interactions between native and mutant neuroligins contributing to disease phenotypes. PMID- 22671296 TI - Two cases of transfusion-transmitted hepatitis B virus (HBV) infection in a low endemic country before implementation of HBV nucleic acid testing. AB - BACKGROUND: The risk of hepatitis B virus (HBV) transmission by transfusion is higher than that of other blood-borne viruses. In France, before the introduction of HBV nucleic acid testing (NAT) in 2010, blood donations were tested for hepatitis B surface antigen (HBsAg) and antibodies against hepatitis B core antigen, and the residual risk of HBV transfusion related to preseroconversion acute phase was estimated at 0.54 per million donations. The additional value of the implementation of a highly sensitive HBV NAT to prevent such transmissions is discussed. STUDY DESIGN AND METHODS: Two lookback investigations based on HBV seroconversion of repeat donors were performed. Donors and recipients were followed up in multiple samples that were tested for HBV serologic and molecular markers. RESULTS: The recipients have shown posttransfusion HBsAg seroconversion. The archived samples from the implicated donations were positive for HBV DNA at extremely low viral load in both cases. HBV isolates from donors and recipients of each case were organized in the same cluster with 100% identities into Genotypes A2 and B4, respectively. One recipient spontaneously recovered from infection while the second was successfully treated. CONCLUSION: The present cases highlight the importance of introducing highly sensitive HBV NAT to prevent transmission. Moreover, the lookback studies based on appropriate molecular and serologic investigations of patients transfused with previous donations from newly identified HBV-infected repeat donors offer the opportunity to treat a recently infected recipient. PMID- 22671297 TI - Why wait 3 months before doing electromyography in obstetric brachial plexus lesions? Challenging the norm. PMID- 22671298 TI - Ultrasonographic adrenal gland measurements in healthy Yorkshire Terriers and Labrador Retrievers. AB - An upper threshold of 7.4 mm for maximal adrenal gland diameter is commonly used to detect pituitary-dependent hyperadrenocorticism ultrasonographically in dogs. There is a substantial overlap between adrenal gland diameter of healthy dogs and of those with pituitary-dependent hyperadrenocorticism. The aim of this study is to determine the measurements of both adrenal glands, in particular, of the height at the caudal glandular pole in a longitudinal plane, in the Labrador retriever and Yorkshire terrier, two breeds widely represented in the population suspected of hyperadrenocorticism. Seventeen Labrador retrievers and 24 Yorkshire terriers considered healthy were included in the study. Adrenal gland measurements were taken on static images and comprised in measurements of the length in a longitudinal plane (L), of the height at the cranial (CrHLG) and caudal pole (CdHLG) in a longitudinal plane and in a transverse plane (CrHTR and CdHTR, respectively), and of the width at the cranial and caudal poles in a transverse plane (CrWTR and CdWTR, respectively). This study established new upper thresholds for the left and right height at the caudal pole measured in a longitudinal plane: 7.9 mm (left) and 9.5 mm (right) for the Labrador retrievers and 5.4 mm (left) and 6.7 mm (right) for the Yorkshire terriers. All the measurements were significantly different between the two breeds. There was a significant relationship between CdHTR and CdHLG, and the age of the dogs for both breeds. PMID- 22671299 TI - The chemoselective reactions of tyrosine-containing G-protein-coupled receptor peptides with [Cp*Rh(H2O)3](OTf)2, including 2D NMR structures and the biological consequences. AB - The bioconjugation of organometallic complexes with peptides has proven to be a novel approach for drug discovery. We report the facile and chemoselective reaction of tyrosine-containing G-protein-coupled receptor (GPCR) peptides with [Cp*Rh(H(2)O)(3)](OTf)(2), in water, at room temperature, and at pH 5-6. We have focused on three important GPCR peptides; namely, [Tyr(1)]-leu-enkephalin, [Tyr(4)]-neurotensin(8-13), and [Tyr(3)]-octreotide, each of which has a different position for the tyrosine residue, together with competing functionalities. Importantly, all other functional groups present, i.e., amino, carboxyl, disulfide, phenyl, and indole, were not prominent sites of reactivity by the Cp*Rh tris aqua complex. Furthermore, the influence of the Cp*Rh moiety on the structure of [Tyr(3)]-octreotide was characterized by 2D NMR, resulting in the first representative structure of an organometallic-peptide complex. The biological consequences of these Cp*Rh-peptide complexes, with respect to GPCR binding and growth inhibition of MCF7 and HT29 cancer cells, will be presented for [(eta(6)-Cp*Rh-Tyr(1))-leu-enkephalin](OTf)(2) and [(eta(6)-Cp*Rh-Tyr(3)) octreotide](OTf)(2). PMID- 22671300 TI - Concurrence of lichen striatus and localised pityriasis rosea: Cutaneous mosaicism. AB - Cutaneous mosaicism has always been an intriguing subject. A 15-year-old boy presented to us with a unilateral band of lesions of pityriasis rosea and lichen striatus. The case is discussed in the light of the concept of genetic mosaicism. PMID- 22671301 TI - Recyclable hypervalent iodine(III) reagent iodosodilactone as an efficient coupling reagent for direct esterification, amidation, and peptide coupling. AB - A hypervalent iodine(III) reagent plays a novel role as an efficient coupling reagent to promote the direct condensation between carboxylic acids and alcohols or amines to provide esters, macrocyclic lactones, amides, as well as peptides without racemization. The regeneration of iodosodilactone (1) can also be readily achieved. The intermediate acyloxyphosphonium ion C from the activation of a carboxylic acid is thought to be involved in the present esterification reaction. PMID- 22671302 TI - Reclaiming the worker role: perceptions of people with mental illness participating in IPS. AB - OBJECTIVE: People with severe mental illness are often successful in gaining work when participating in the evidence-based Individual Placement and Support (IPS) approach. Little evidence exists on how starting work is perceived by IPS participants. This qualitative study aimed to explore how IPS participants perceived working and the work environment to impact on their work performance. METHODS: Nineteen participants starting work in mainstream work settings were interviewed. Questions from the Work Environment Impact Scale were used and data was analysed by content analysis. The participants strove to fit in by coping with environmental demands and adapting to their worker role. RESULTS: Work was perceived as having a positive impact on their daily life, although starting work was perceived as a challenge and the mental illness affected work performance. Personal strategies were needed in order to cope. They perceived both supportive and demanding factors in their work environments, such as the employer's support and the social atmosphere among colleagues. CONCLUSION: The study showed that it is vital to focus on the individual's own strategies for adapting to the worker role when designing the support, as well as to develop collaborative relationships with employers and to optimize the match between the individual and the demands of the work environment. PMID- 22671303 TI - Congenital Bednar tumor over 10 years. PMID- 22671304 TI - Food incentives improve adherence to tuberculosis drug treatment among homeless patients in Russia. AB - The aim of the study was to evaluate the impact of food incentives on adherence to tuberculosis (TB) drug treatment among homeless patients with TB. Food packages were thus given as a part of directly observed therapy to 142 homeless patients with TB at a dispensary in Saint Petersburg, Russian Federation. In addition, a social worker provided the patients with information and legal assistance, for example help with internal passports. Among the 142 patients, 66 were included in the study at the dispensary during their entire treatment period, while 76 patients were included in the study during shorter periods mainly because of transfer to inpatient care. In the first group, 59% of the patients continued the TB drug treatment without interruption in contrast to 31% in a control group. In the second group, that is those studied during shorter periods, 95% continued the TB drug treatment without interruption while attached to the dispensary. Food was introduced in the TB programme of the City of St. Petersburg as a consequence of this study. In conclusion, it can be stated that the food incentive had a strong positive impact on the adherence to TB drug treatment among these socially marginalized patients. The social support contributed in all probability also to the positive results. PMID- 22671305 TI - Thieno analogues of RNA nucleosides: a detailed theoretical study. AB - We use first-principles density functional theory calculations to investigate the structural, energetic, bonding aspects, and optical properties of recently synthesized thieno-analogues of RNA nucleosides. The results are compared against the findings obtained for both the natural nucleosides as well as available experimental data. We find that the modified nucleosides form the hydrogen bonded Watson-Crick (WC) base pairing with similar H-bonding energy as obtained for the natural nucleosides. We have calculated and compared the charge transfer integrals for the H-bonded natural and thieno-modified nucleosides. We find that the thieno modification of these nucleosides strongly affects the charge transfer integrals due to the difference in extent of orbital delocalization in these two types of nucleosides. We also find that the degree of reduction of charge transfer integrals is larger for the H-bonded A-U pair than in the G-C pair. We also focus on the optical absorption properties of these thieno-modified nucleosides and their WC H-bonded base pairs in gas phase as well as with implicit water. Our calculated results show that the low energy peaks in the absorption spectra mainly arise because of the pi-pi* electronic transition for both the nucleosides, and the observed red shift for thieno-nucleosides compared to natural nucleosides are consistent with the calculated decrease in electronic gaps. Our results demonstrate that the thieno modification of natural nucleosides significantly modifies their electronic and optical properties, although the basic structural and bonding aspects remained the same. It also gives a microscopic understanding of the experimentally observed optical behaviors. PMID- 22671306 TI - Architecture of CuS/PbS heterojunction semiconductor nanowire arrays for electrical switches and diodes. AB - CuS/PbS p-n heterojunction nanowires arrays have been successfully synthesized. Association of template and DC power sources by controllable electrochemistry processes offers a technique platform to efficiently grow a combined heterojunction nanowire arrays driven by a minimization of interfacial energy. The resulting p-n junction materials of CuS/PbS show highly uniform 1D wire architecture. The single CuS/PbS p-n heterojunction nanowire based devices were fabricated, and their electrical behaviors were investigated. The independent nanowires exhibited a very high ON/OFF ratio of 1195, due to the association effect of electrical switches and diodes. PMID- 22671307 TI - Hesperidin attenuates brain biochemical changes of irradiated rats. AB - PURPOSE: The purpose of this study was to evaluate the efficacy of hesperidin (HES), a citrus flavonoid, against the severity of biochemical disorders in the cerebral hemispheres of irradiated rats. MATERIAL AND METHODS: Hesperidin (50 mg/kg body weight) was administered to male albino rats via gavages during 10 successive days before whole body exposure to gamma rays (5 Gy) and during 14 days after irradiation. The animals were sacrificed on the 14th day post irradiation. RESULTS: The results demonstrated a significant increase of the levels of thiobarbituric acid reactive substances (TBARS), protein carbonyls (CO), and advanced oxidation protein products (AOPP), associated to significant decreases of total superoxide dismutase (tSOD) and catalase (CAT) activities, and reduced thiols content in the cerebral hemispheres of irradiated rats indicating oxidative stress. A significant decrease of the serotonin (5-HT), dopamine (DA), norepinephrine (NE) and epinephrine (EPI) contents and a significant increase of the activity of monoamine oxidase (MAO) were recorded, also, indicating alterations in the metabolism of monoamines. Moreover, a significant decrease of the activities of glutamate dehydrogenase (GDH) and creatine phophokinase (CPK), and a significant increase of calcium ions (Ca (+2)) levels were recorded in the mitochondria. Hesperidin treatment has significantly attenuated oxidative stress, monoamines alterations and mitochondrial damage in the cerebral hemispheres of irradiated rats. CONCLUSION: It could be concluded that hesperidin might attenuate the severity of radiation-induced biochemical disorders in brain tissues. PMID- 22671308 TI - Role of platelets as mediators that link inflammation and thrombosis in atherosclerosis. AB - Platelets, crucial mediators of the acute complications of atherosclerosis that cause life-threatening ischemic events at late stages of the disease, are also key effectors of inflammation throughout plaque development through their interaction with endothelial and immune cells in the injured vessel wall. During the first steps of atherosclerosis, blood inflammatory leukocytes interact with the damaged endothelium in areas rich in platelet aggregates. In late stages of the disease, platelets secrete several inflammatory molecules, even without forming aggregates. These molecules exacerbate the inflammation and induce the transition from chronic to acute disease, featuring increased instability of the atherosclerotic lesion that results in plaque rupture and thrombosis. Moreover, platelets play an important role in vascular wall remodeling induced by chronic inflammation by controlling vascular cell differentiation and proliferation. In this review, we discuss the role of platelets as cell mediators that link inflammation and thrombosis in atherosclerotic disease and their potential in the development of new therapeutic tools to fight cardiovascular disease. PMID- 22671309 TI - Defining the normal acetabular vault in adult males and females using a novel three-dimensional model. AB - The management and quantification of bone loss is a major challenge in primary and revision total hip replacement. Defining the normal three-dimensional (3D) anatomy of the acetabular vault could aid in assessing pathologic changes and in designing prosthetic joint components. We performed a quantitative assessment of normal 3D acetabular vault structure to define the shape and location of weight bearing acetabular bone referred to as the vault. Images from 70 normal hip computed tomography images were used to define the 3D acetabular vault anatomy and develop a 3D model. Variation in vault shape was quantified by measuring the distance between every surface point on a subject's hemipelvis and the reference vault. Variation among different hip alignments was assessed using 19 scans from subjects with varus, valgus and dysplastic hip morphologies. The acetabular vault model had 96.6% (95% CI: 91.7-101.5), 97.8% (95% CI: 94.5-101.1) and 96.4% (95% CI: 98.7-94.1) of the surface points within 3 mm of normal male, normal female and abnormal hip specimens, respectively. Comparison of acetabular vault model fit between gender and hip types revealed that it was only significantly different between normal males and normal females (P = 0.0194) and between normal males and dysplastic females (P = 0.0377). A conserved 3D acetabular vault shape and location exists that can accommodate various hip morphologies. Defining a normal vault may increase the precision with which hip pathology can be identified and may also serve as a preoperative assessment tool for planning total hip arthroplasty. PMID- 22671310 TI - Treatment of acne scarring with fractional CO2 laser. AB - BACKGROUND: Fractional ablative CO(2) laser therapy is based on the theory of fractional photothermolysis. It can be effective in treating acne scars in a less invasive fashion than conventional ablative CO(2) laser therapy. OBJECTIVE: In this clinical study, the safety and efficacy of a novel CO(2) fractional ablative laser was investigated for the treatment of facial atrophic acne scarring in Chinese individuals. MATERIALS AND METHODS: A total of 31 patients (11 females, 20 males, Fitzpatrick skin phototypes III-IV) with facial acne scarring received three sequential fractional treatments over a 6-month period. Outcome measurements included blinded evaluations of before and after photographs by two physicians at 3 and 12 months after the final treatment. Global improvement was noted as well as any untoward events. RESULTS: At the 12 months follow-up time period, 12.9% of the patients showed excellent improvement in their acne scars, while 38.71% noted good to fair results. The clinical response at the 12-month follow-up visit tended to be better than at the 3-month follow-up visit, but was not statistically significant. Four patients experienced post-treatment and transient PIH but three patients were noted to have prolonged erythema. There was no evidence hypopigmentation or worsening of the scarring in any of the study patients. CONCLUSION: This high-energy pulsed and cool-scanned fractional ablative CO(2) laser system is safe and effective for facial atrophic acne scarring. Improvement in scarring was noted in the majority of patients with minimal discomfort and minimal downtime. Continued improvement over time is also an important clinical finding. PMID- 22671311 TI - A Web-based approach to blood donor preparation. AB - BACKGROUND: Written and video approaches to donor education have been shown to enhance donation attitudes and intentions to give blood, particularly when the information provides specific coping suggestions for donation-related concerns. This study extends this work by comparing Web-based approaches to donor preparation among donors and nondonors. STUDY DESIGN AND METHODS: Young adults (62% female; mean [+/-SD] age, 19.3 [+/-1.5] years; mean [range] number of prior blood donations, 1.1 [0-26]; 60% nondonors) were randomly assigned to view 1) a study Web site designed to address common blood donor concerns and suggest specific coping strategies (n = 238), 2) a standard blood center Web site (n = 233), or 3) a control Web site where participants viewed videos of their choice (n = 202). Measures of donation attitude, anxiety, confidence, intention, anticipated regret, and moral norm were completed before and after the intervention. RESULTS: Among nondonors, the study Web site produced greater changes in donation attitude, confidence, intention, and anticipated regret relative to both the standard and the control Web sites, but only differed significantly from the control Web site for moral norm and anxiety. Among donors, the study Web site produced greater changes in donation confidence and anticipated regret relative to both the standard and the control Web sites, but only differed significantly from the control Web site for donation attitude, anxiety, intention, and moral norm. CONCLUSION: Web-based donor preparation materials may provide a cost-effective way to enhance donation intentions and encourage donation behavior. PMID- 22671312 TI - Diversity and distribution of fungal communities in lakes of Antarctica. AB - This study assessed the diversity and distribution of filamentous fungi obtained from water sampled from six lakes in the Antarctic Peninsula. One hundred and twenty-eight fungal isolates were purified and identified by analysis of nuclear rDNA ITS region sequences as belonging to 31 fungal different operational taxonomic units (OTUs). The most frequently isolated fungi were Geomyces pannorum and Mortierella sp.; these species occurred in six and three of the lakes sampled, respectively, and displayed the highest total colony-forming unit per L. Different species that have not been found to these lakes and/or had adapted to cold conditions were found. In general, the fungal community displayed low richness and high dominance indices. The species Cadophora cf. luteo-olivacea, Cadophora malorum, Davidiella tassiana, G. pannorum, Mortierella cf. alpina and Thelebolus cf. microsporus that were found in the lakes in question were also previously found in other cold ecosystems, such as Arctic, temperate and Alpine regions. The results of this study suggest the presence of an interesting aquatic fungal web, including symbionts, weak and strong saprophytes and parasite/pathogen fungal species. This aquatic web fungal may be a useful community model for further ecological and evolutionary studies of extreme habitats. PMID- 22671313 TI - The early changes in trunk muscle strength and disability following lumbar spine fusion. AB - PURPOSE: To analyze trunk muscle function pre- and postoperatively in patients undergoing lumbar spine fusion. Associations between changes in trunk muscle strength and disability were also studied. METHOD: A total of 114 patients undergoing lumbar spine fusion participated in the study. The flexion and extension strength of the trunk was measured preoperatively and 3 months after surgery using a strain-gauge dynamometer. Disability and pain during the past week was evaluated with the Oswestry disability index (ODI) and visual analog scale (VAS), respectively. RESULTS: Preoperative trunk extension and flexion strength levels were 319 N and 436 N in males, respectively, and 160 N and 214 N in females, respectively. In females 3 months postoperatively, the trunk extension strength increased by 39 N (p < 0.001) and flexion by 38N (p < 0.001), whereas it remained unchanged in males. The preoperative extension/flexion strength ratio was 0.79 in females and 0.76 in males. Three months postoperatively, the strength ratio decreased to 0.66 in males (p = 0.02). The mean ODI improved by 47% and back pain decreased by 65% (both p < 0.001). The changes in the ODI correlated with changes in trunk extension (r = -0.38) and flexion (r = -0.43) strength. CONCLUSIONS: Patients undergoing lumbar spine fusion had low trunk muscle strength and strength imbalance. Back fusion surgery leads to considerable relief of pain and disability, but patients still have low trunk extension and flexion strength levels 3 months postoperatively. Therefore, there is need for a proper progressive strength training protocols to normalize back function. PMID- 22671314 TI - TRPA1-like channels enhance glycinergic transmission in medullary dorsal horn neurons. AB - The effect of icilin, a potent agonist of transient receptor potential ankyrin 1 (TRPA1) and TRPM8, on glycinergic transmission was examined in mechanically isolated rat medullary dorsal horn neurons by use of the conventional whole-cell patch-clamp technique. Icilin increased the frequency of glycinergic spontaneous miniature inhibitory post-synaptic currents (mIPSCs) in a dose-dependent manner. Either allyl isothiocyanate(AITC) or cinnamaldehyde, other TRPA1 agonists, also increased mIPSC frequency, but the extent of facilitation induced by AITC or cinnamaldehyde was less than that induced by icilin. However, menthol, a TRPM8 agonist, had no facilitatory effect on glycinergic mIPSCs. The icilin-induced increase in mIPSC frequency was significantly inhibited by either HC030031, a selective TRPA1 antagonist, or ruthenium red, a non-selective transient receptor potential channel blocker. Icilin failed to increase glycinergic mIPSC frequency in the absence of extracellular Ca(2+), suggesting that the icilin-induced increase in mIPSC frequency is mediated by the Ca(2+) influx from the extracellular space. In contrast, icilin still increased mIPSC frequency either in the Na(+) -free external solution or in the presence of Cd(2+), a general voltage-dependent Ca(2+) channel blocker. The present results suggest that icilin acts on pre-synaptic TRPA1-like ion channels, which are permeable to Ca(2+), to enhance glycinergic transmission onto medullary dorsal horn neurons. The TRPA1 like channel-mediated enhancement of glycinergic transmission in medullary dorsal horn neurons would contribute to the regulation of pain information from the peripheral tissues. PMID- 22671423 TI - Gender differences in the anatomy of the perineal glands in Guinea pigs and the effect of castration. AB - Perineal glands in guinea pigs are part of the sebaceous glandular complex. Their secretions are used for scent marking. This is important for social status and can be seen in both sexes and castrated males. Discrepancy exits about the existence of these glands in female guinea pigs and knowledge of the anatomical consequences of castration on the male perineal glands is sparse. To examine these uncertainties related to gender, perineal glands from 13 sexually mature pet guinea pigs were examined macro- and microscopically. Clear gender differences in the anatomy of perineal glands were found, and castrated males showed signs of atrophy and fatty infiltration in the glands. Females do have perineal glands, although smaller than the glands in the male. The glands are typically sebaceous with multiple excretory ducts. A macroscopic unique feature in the males was the clearly evident orifices of a large excretory duct on each side of the slightly everted perineal sac. However, the reason for this gender difference is not clear. In castrated males, the orifices were atrophied and difficult to see. In addition, the sebaceous glands of the hair follicles in the skin folds of the perineal opening were smaller and less abundant in females and castrated males. The changes in castrated males are presumably linked to the hormonal changes and decreased secretion after castration. The dense keratin layer in the perineal sac was thicker in males than in both castrated males and females and could contribute to the concrement formation seen mainly in males. PMID- 22671424 TI - "Unifying the definitions of sudden unexpected death in epilepsy": a pediatric perspective. PMID- 22671425 TI - Rupture of thin liquid films induced by impinging air-jets. AB - Thin liquid films on partially wetting substrates are subjected to laminar axisymmetric air-jets impinging at normal incidence. We measured the time at which film rupture occurs and dewetting commences as a function of diameter and Reynolds number of the air-jet. We developed numerical models for the air flow as well as the height evolution of the thin liquid film. The experimental results were compared with numerical simulations based on the lubrication approximation and a phenomenological expression for the disjoining pressure. We achieved quantitative agreement for the rupture times. We found that the film thickness profiles were highly sensitive to the presence of minute quantities of surface active contaminants. PMID- 22671427 TI - Chronic kidney disease and vascular remodelling: molecular mechanisms and clinical implications. AB - CKD (chronic kidney disease) is a severe and complex disease with a very high prevalence of CV (cardiovascular) complications. CKD patients are exposed to haemodynamic disturbances in addition to severe metabolic abnormalities that lead to a specific form of arterial remodelling, which contributes to the development of CV disease. Arterial calcification is a major event in the arterial remodelling process and is strongly linked to mineral metabolism abnormalities associated with CKD. Arterial remodelling is not limited to arterial calcification and modifications in arterial wall composition are also observed. Activation of the RAS (renin-angiotensin system), ET-1 (endothelin-1), endothelial dysfunction, oxidative stress and ADMA (asymmetric omega-NG,NG dimethylarginine), as well as the anti-aging molecule Klotho, are implicated in this process. The present review details the mechanisms involved in arterial calcification and arterial remodelling associated with CKD, and provides the clinical consequences of large and small artery stiffness and remodelling in CKD patients. PMID- 22671426 TI - Role of adrenal glucocorticoid signaling in prefrontal cortex gene expression and acute behavioral responses to ethanol. AB - BACKGROUND: Glucocorticoid hormones modulate acute and chronic behavioral and molecular responses to drugs of abuse including psychostimulants and opioids. There is growing evidence that glucocorticoids might also modulate behavioral responses to ethanol ( EtOH ). Acute EtOH activates the hypothalamic-pituitary adrenal axis, causing the release of adrenal glucocorticoid hormones. Our prior genomic studies suggest that glucocorticoids play a role in regulating gene expression in the prefrontal cortex (PFC) of DBA2/J (D2) mice following acute EtOH administration. However, few studies have analyzed the role of glucocorticoid signaling in behavioral responses to acute EtOH . Such work could be significant, given the predictive value for the level of response to acute EtOH in the risk for alcoholism. METHODS: We studied whether the glucocorticoid receptor (GR) antagonist, RU-486, or adrenalectomy (ADX) altered male D2 mouse behavioral responses to acute (locomotor activation, anxiolysis, or loss-of righting reflex [LORR]) or repeated (sensitization) EtOH treatment. Whole-genome microarray analysis and bioinformatics approaches were used to identify PFC candidate genes possibly responsible for altered behavioral responses to EtOH following ADX. RESULTS: ADX and RU-486 both impaired acute EtOH (2 g/kg)-induced locomotor activation in D2 mice without affecting basal locomotor activity. However, neither ADX nor RU-486 altered the initiation of EtOH sensitization (locomotor activation or jump counts), EtOH -induced anxiolysis, or LORR. ADX mice showed microarray gene expression changes in PFC that significantly overlapped with acute EtOH -responsive gene sets derived by our prior microarray studies. Q-rtPCR analysis verified that ADX decreased PFC expression of Fkbp5 while significantly increasing Gpr6 expression. In addition, high-dose RU-486 pretreatment blunted EtOH -induced Fkbp5 expression. CONCLUSIONS: Our studies suggest that EtOH 's activation of adrenal glucocorticoid release and subsequent GR activation may partially modulate EtOH 's acute locomotor activation in male D2 mice. Furthermore, because adrenal glucocorticoid basal tone regulated PFC gene expression, including a significant set of acute EtOH -responsive genes, this suggests that glucocorticoid-regulated PFC gene expression may be an important factor modulating acute behavioral responses to EtOH . PMID- 22671428 TI - Magnesium and its transporters in cancer: a novel paradigm in tumour development. AB - The relationship between magnesium and cancer is not as simple as could be assumed from the well-established requirement of magnesium for cell proliferation. Basic and pre-clinical studies indicate that magnesium deficiency can have both anti- and pro-tumour effects. In the present review, we briefly outline the new findings on the role of magnesium in angiogenesis and metastatization, and focus on the relationship between tumour cell proliferation and metabolic reprogramming, discussing how magnesium and its transporters are involved in these processes. The role of magnesium in cancer is also critically examined with regard to mitochondrial function, apoptosis and resistance to treatment. Finally, we bring together the latest experimental evidence indicating that alteration in the expression and/or activity of magnesium channels is a frequent finding in cancer cells and human tumour tissues examined to date, and we discuss the potential implications for developing novel diagnostic and therapeutic strategies. PMID- 22671430 TI - Chiral phosphoric acid catalyzed inverse-electron-demand aza-Diels-Alder reaction of isoeugenol derivatives. AB - Highly enantio- and diastereoselective three-component inverse electron-demand aza-Diels-Alder reaction of aldehydes, anilines, and isoeugenol derivatives catalyzed by a chiral phosphoric acid catalyst are reported. A wide variety of 2,3,4-trisubstituted tetrahydroquinolines containing an aryl group at the 4 position were obtained in a one-pot process with good to high yields and excellent stereoselectivities (>95:5 dr and up to >99% ee). PMID- 22671431 TI - Management pathway of skin conditions presenting to an Australian tertiary hospital emergency department. AB - There have been limited published data on the management pathway of patients presenting to the emergency department with skin conditions. We report the pathway of patients presenting with skin conditions to a large tertiary hospital for 1 year and make recommendations to optimise the available dermatological services. PMID- 22671429 TI - Toll-like receptor 9 activation: a novel mechanism linking placenta-derived mitochondrial DNA and vascular dysfunction in pre-eclampsia. AB - Emerging evidence suggests that in addition to being the 'power houses' of our cells, mitochondria facilitate effector responses of the immune system. Cell death and injury result in the release of mtDNA (mitochondrial DNA) that acts via TLR9 (Toll-like receptor 9), a pattern recognition receptor of the immune system which detects bacterial and viral DNA but not vertebrate DNA. The ability of mtDNA to activate TLR9 in a similar fashion to bacterial DNA stems from evolutionarily conserved similarities between bacteria and mitochondria. mtDNA may be the trigger of systemic inflammation in pathologies associated with abnormal cell death. PE (pre-eclampsia) is a hypertensive disorder of pregnancy with devastating maternal and fetal consequences. The aetiology of PE is unknown and removal of the placenta is the only effective cure. Placentas from women with PE show exaggerated necrosis of trophoblast cells, and circulating levels of mtDNA are higher in pregnancies with PE. Accordingly, we propose the hypothesis that exaggerated necrosis of trophoblast cells results in the release of mtDNA, which stimulates TLR9 to mount an immune response and to produce systemic maternal inflammation and vascular dysfunction that lead to hypertension and IUGR (intra-uterine growth restriction). The proposed hypothesis implicates mtDNA in the development of PE via activation of the immune system and may have important preventative and therapeutic implications, because circulating mtDNA may be potential markers of early detection of PE, and anti-TLR9 treatments may be promising in the management of the disease. PMID- 22671432 TI - The role of information technology as a complementary resource in healthcare integrated delivery systems. AB - As in many industries, it is recognized that there is a need to increase the use of information technology (IT) in the healthcare industry. However, until now, this has not occurred. In fact, some say that IT in healthcare has consistently fallen far short of expectations. The purpose of this study was to illuminate the need for a more holistic view of healthcare network integration and demonstrate that simply applying the latest technology to the network is not adequate for improving overall effectiveness. The study results showed that the more holistic view has to include management commitment, of complementarity between IT integration and organizational integration, and continued investments. PMID- 22671433 TI - The emergence and potential impact of medicine 2.0 in the healthcare industry. AB - Medicine 2.0 has emerged within healthcare information technology to enable more defined relationships among providers and patients. Physicians, hospitals, and patients are using Medicine 2.0 through social networking to maintain their foothold in the evolution of medical technologies. The authors' purpose was to determine potential improvements that Medicine 2.0 has on communication and collaboration of healthcare information. Research has shown that Medicine 2.0 has integrated into the healthcare industry and is enabling an increase in communication in healthcare matters. The provider-patient relationship is improving through the use of Medicine 2.0 and has positively impacted society so far. PMID- 22671434 TI - Our VOICE: an interdisciplinary approach to shared governance. AB - The authors' purpose was to make public to other healthcare executives the demonstrated success of an interdisciplinary shared governance process benefiting any healthcare organization. Main components of a successful model include a conducive work environment free of distractions, available resources in order to gather information to complete a project, and committees chosen focused on high priority for patient and staff satisfaction, quality, and safety. An essential piece of the puzzle is that grassroots staff needs to own the process. The authors share the current model and discuss outcomes, success, and lessons learned throughout their decade-long journey. PMID- 22671435 TI - An integrated lean-methods approach to hospital facilities redesign. AB - Lean production methods for eliminating waste and improving processes in manufacturing are now being applied in healthcare. As the author shows, the methods are appropriate for redesigning hospital facilities. When used in an integrated manner and employing teams of mostly clinicians, the methods produce facility designs that are custom-fit to patient needs and caregiver work processes, and reduce operational costs. The author reviews lean methods and an approach for integrating them in the redesign of hospital facilities. A case example of the redesign of an emergency department shows the feasibility and benefits of the approach. PMID- 22671437 TI - Orbital parasitosis. AB - Orbital parasitoses are uncommon diseases. Due to specific characteristics of orbital space, many different diseases, such as tumors and inflammatory disease, can present with similar clinical manifestations. The aim of this study is to review the most important clinical, epidemiological, and treatment aspects of orbital parasitoses described worldwide. PMID- 22671438 TI - PHACE syndrome associated with club foot and thumb-in-palm deformity. PMID- 22671439 TI - Caregiving appraisal and disease activity in early inflammatory arthritis. AB - OBJECTIVE: The caregiving process accompanying inflammatory arthritis can be stressful to both caregivers and care recipients. In this study, we examined how caregiving involvement and caregiving appraisal as perceived by both patients and their caregiving spouses relate to disease activity and mental health of patients in early inflammatory arthritis. METHODS: Patients in the early phase (> 6 weeks, <18 months duration) of inflammatory arthritis were recruited from a larger early inflammatory arthritis registry, which recorded sociodemographic data and disease characteristics. Disease activity was measured with the Disease Activity Score in 28 joints (DAS28). Current depressive symptoms were measured using the Center for Epidemiologic Studies - Depression Mood Scale. Patient and spouse perceived caregiving involvement and caregiving appraisal were assessed using the Caregiving Involvement Questionnaire and Caregiving Appraisal Scale, respectively. RESULTS: The study sample consisted of 73 patients living with spouse. Mean age was 54 years, 64.4% were women and mean illness duration was 7.48 months. Patients' positive caregiving appraisal was associated with less disease activity (DAS28) (p = 0.003) and less total depressive mood (p < 0.001). In multivariate analysis, patients' appraisal of the caregiving context was negatively associated with disease activity (DAS28) after controlling for caregiving involvement and depression (p = 0.035). CONCLUSION: This study indicates that, in early inflammatory arthritis, patients' caregiving appraisal might be important to consider when assessing disease activity. Clinicians are encouraged to include both patients and their spouse caregivers in interventions. PMID- 22671440 TI - Rates of water exchange on the [Fe4(OH)2(hpdta)2(H2O)4]0 molecule and its implications for geochemistry. AB - The ammonium salt of [Fe(4)O(OH)(hpdta)(2)(H(2)O)(4)](-) is soluble and makes a monospecific solution of [Fe(4)(OH)(2)(hpdta)(2)(H(2)O)(4)](0)(aq) in acidic solutions (hpdta = 2-hydroxypropane-1,3-diamino-N,N,N',N'-tetraacetate). This tetramer is a diprotic acid with pK(a)(1) estimated at 5.7 +/- 0.2 and pK(a)(2) = 8.8(5) +/- 0.2. In the pH region below pK(a)(1), the molecule is stable in solution and (17)O NMR line widths can be interpreted using the Swift-Connick equations to acquire rates of ligand substitution at the four isolated bound water sites. Averaging five measurements at pH < 5, where contribution from the less-reactive conjugate base are minimal, we estimate: k(ex)(298) = 8.1 (+/-2.6) * 10(5) s(-1), DeltaH(++) = 46 (+/-4.6) kJ mol(-1), DeltaS(++) = 22 (+/-18) J mol(-1) K(-1), and DeltaV(++) = +1.85 (+/-0.2) cm(3) mol(-1) for waters bound to the fully protonated, neutral molecule. Regressing the experimental rate coefficients versus 1/[H(+)] to account for the small pH variation in rate yields a similar value of k(ex)(298) = 8.3 (+/-0.8) * 10(5) s(-1). These rates are ~10(4) times faster than those of the [Fe(OH(2))(6)](3+) ion (k(ex)(298) = 1.6 * 10(2) s(-1)) but are about an order of magnitude slower than other studied aminocarboxylate complexes, although these complexes have seven-coordinated Fe(III), not six as in the [Fe(4)(OH)(2)(hpdta)(2)(H(2)O)(4)](0)(aq) molecule. As pH approaches pK(a1), the rates decrease and a compensatory relation is evident between the experimental DeltaH(++) and DeltaS(++) values. Such variation cannot be caused by enthalpy from the deprotonation reaction and is not well understood. A correlation between bond lengths and the logarithm of k(ex)(298) is geochemically important because it could be used to estimate rate coefficients for geochemical materials for which only DFT calculations are possible. This molecule is the only neutral, oxo-bridged Fe(III) multimer for which rate data are available. PMID- 22671441 TI - Chronic low dose UV exposure and p53 mutation: tilting the odds in early epidermal preneoplasia? AB - PURPOSE: This review addresses how mutation of the TP53 gene (p53) and ultraviolet light alter the behavior of normal progenitor cells in early epidermal preneoplasia. CONCLUSIONS: Cancer is thought to evolve from single mutant cells, which expand into clones and ultimately into tumors. While the mutations in malignant lesions have been studied intensively, less is known about the earliest stages of preneoplasia, and how environmental factors may contribute to drive expansion of mutant cell clones. Here we review the evidence that ultraviolet radiation not only creates new mutations but drives the exponential growth of the numerous p53 mutant clones found in chronically exposed epidermis. Published data is reconciled with a new paradigm of epidermal homeostasis which gives insights into the behavior of mutant cells. We also consider the reasons why so few mutant cells progress into tumors and discuss the implications of these findings for cancer prevention. PMID- 22671442 TI - Transference of atmospheric hydroxyl radical to the ocean surface induces high phytoplankton cell death. AB - Hydroxyl radical (OH), the main atmospheric oxidant at the global scale, is believed to play an important role in the dynamics of dissolved organic matter in the sea. Herein, we provide evidence, on the basis of seven experiments performed in contrasting ecosystems (subtropical NE Atlantic and Antarctic waters), of high fluxes of atmospheric OH into the surface oceanic layer, particularly during afternoon events. The experiments demonstrated a tight negative relationship between phytoplankton abundance and the concentration of OH in surface seawater, with acute cell death during afternoon atmospheric OH influx events. The effect of OH radical was higher for picophytoplankton organisms, with Prochlorococcus showing the highest decay rate and the shortest half-life among the phytoplankton populations habiting the ocean surface layers. Our results provide evidence for a high toxicity of atmospheric-derived OH radical to phytoplankton of the surface layer of the ocean. PMID- 22671516 TI - The phosphodiesterase-4 (PDE4) inhibitor rolipram decreases ethanol seeking and consumption in alcohol-preferring Fawn-Hooded rats. AB - BACKGROUND: Alcohol dependence is a complex psychiatric disorder demanding development of novel pharmacotherapies. Because the cyclic adenosine monophosphate (cAMP) signaling cascade has been implicated in mediating behavioral responses to alcohol, key components in this cascade may serve as potential treatment targets. Phosphodiesterase-4 (PDE4), an enzyme that specifically catalyzes the hydrolysis of cAMP, represents a key point in regulating intracellular cAMP levels. Thus, it was of interest to determine whether PDE4 was involved in the regulation of alcohol use and abuse. METHODS: Male Fawn-Hooded (FH/Wjd) rats were tested for 5% (v/v) ethanol (EtOH) and 10% (w/v) sucrose operant oral self-administration following treatment with the selective PDE4 inhibitor rolipram (0.0125, 0.025, or 0.05 mg/kg, subcutaneous [s.c.]); rolipram at higher doses (0.05, 0.1, and 0.2 mg/kg, s.c.) was tested to determine its impact on the intake of EtOH, sucrose, or water using the 2-bottle choice drinking paradigm. Subsequent open-field testing was performed to evaluate the influence of higher doses of rolipram on locomotor activity. RESULTS: Acute administration of rolipram dose-dependently reduced operant self-administration of 5% EtOH, but had no effect on 10% sucrose responding. Time-course assessment revealed significant decreases in EtOH consumption after rolipram (0.1, 0.2 mg/kg) treatment in continuous- and intermittent access to EtOH at 5% or 10%, respectively. Moreover, chronic rolipram treatment time-dependently decreased 5% EtOH consumption and preference during treatment days and after the termination of rolipram administration. Rolipram at the highest doses (0.1 and 0.2 mg/kg) did decrease locomotor activity, but the effect lasted only 10 and 20 minutes, respectively, which did not likely alter long-term EtOH drinking. CONCLUSIONS: These results suggest that PDE4 plays a role in alcohol seeking and consumption behavior. Drugs interfering with PDE4 may be a potential pharmacotherapy for alcohol dependence. PMID- 22671517 TI - Normal nasal cavity and paranasal sinuses in brown lemurs Eulemur fulvus: computed tomography and cross-sectional anatomy. AB - BACKGROUND: Far less is known about the normal anatomy of the nasal cavity of Eulemur fulvus; no computed tomography (CT) scan has ever been published. METHODS: Relevant CT scans were taken in the transverse, dorsal and longitudinal planes. These scans were compared with anatomical sections of heads. RESULTS: Computed tomography scans revealed almost all nasal structures, but cannot differentiate between the various layers of the nasal mucosa. Results show a double-scroll arrangement of the ventral nasal concha. The dorsal nasal concha protrudes into the maxillary sinus, but no protrusion into the frontal sinus was observed. The ethmoturbinate I is completely closed back on itself and rostrally voluminous. CONCLUSIONS: This work shows that at a clinical level, the integrity of the different turbinates can easily be appreciated from a simple CT scan. It will assist clinicians to evaluate pathological conditions that affect the nasal region. PMID- 22671518 TI - Four methods of evaluation of facial erythema and pigment treated with intense pulsed light or cream. AB - AIM: To evaluate methods of evaluation of patients with mild to moderate facial pigmentation or erythema and compare clinical and photographic grading with instrumental evaluation. METHODS: Of the 24 female subjects treated, 12 were treated with intense pulsed light (IPL) and 12 were treated with daily cream program. Evaluations before and at 16 weeks consisted of: 1. Clinical examination and severity grading by a dermatologist without knowledge of treatment given. 2. Standardised photographs were evaluated by two other dermatologists without knowledge of treatment given. 3. A computer controlled photographic skin analysis systems was used to grade severity of erythema and pigmentation. 4. Subjects were asked to assess their response at the end of a 16-week period, that is, subject self-evaluation. RESULTS: On clinical evaluation of IPL subjects, 12 showed improvement. Of the cream subjects, 11 showed improvement. There was correlation between dermatologist facial examination and the instrumental method. Overall the different assessments showed a slightly greater trend for improvement with IPL treatments for erythema and pigmentation, but no statistical differences were found between the treatments using Student's t-test and Anova analysis of comparative improvement. PMID- 22671519 TI - Alterations in the sarcoplasmic protein fraction of beef muscle with postmortem aging and hydrodynamic pressure processing. AB - Capillary electrophoresis (CE) and reversed-phase high performance liquid chromatography (RP-HPLC) analyses were utilized to detect differences in the sarcoplasmic protein fractions of beef strip loins subjected to aging and hydrodynamic pressure processing (HDP) treatments. At 48 h postmortem, strip loins (n = 12) were halved and subjected to control or HDP treatments. Following treatment, each half was divided into 3 portions which were aged for 0, 5, and 8 d. After each aging period, steaks were removed for Warner-Bratzler shear force (WBSF) analysis and for the extraction of sarcoplasmic proteins which were analyzed by CE and RP-HPLC. Aging by HDP interactions were not detected using either separation technique. With CE analysis, no HDP effects were observed; however, the relative peak area of 8 protein peaks ranging in size from 17 to >200 kDa were influenced by postmortem aging. Separation of proteins by RP-HPLC demonstrated that HDP influenced the relative size of 2 protein peaks while postmortem aging effects were observed in 6 peaks. Alterations in the sarcoplasmic protein fractions detected by both CE and RP-HPLC were correlated to WBSF measurements. Overall, data demonstrate that HDP has minimal effects on sarcoplasmic proteins and that aging related changes in the water soluble protein fractions of muscle may be useful as indirect indicators of beef tenderness. PRACTICAL APPLICATION: Using 2 different postmortem tenderization techniques, aging and hydrodynamic pressure processing, this study demonstrates that postmortem changes in the soluble protein fraction of beef may be useful as potential indicators of meat tenderness. PMID- 22671520 TI - Use of UV-C treatments to maintain quality and extend the shelf life of green fresh-cut bell pepper (Capsicum annuum L.). AB - The objective of this work was to select a Ultraviolet-C (UV-C) treatment for fresh-cut mature green bell pepper, and to evaluate the effect of its combination with refrigeration on quality maintenance. Bell pepper sticks were treated with 0, 3, 10, or 20 kJ/m2 UV-C in the outer (O), inner (I), or both sides of the pericarp (I/O) and stored for 8 d at 10 degrees C. During the first 5 d of storage, all UV-C treatments reduced deterioration as compared to the control. The treatment with 20 kJ/m2 I/O was the most effective to reduce deterioration, and was used for further evaluations. In a second group of experiments, mature green bell pepper sticks were treated with 20 kJ/m2 I/O, stored at 5 degrees C for 7 or 12 d and assessed for physical and chemical analysis, and microbiological quality. UV-C-treated fruit showed lower exudates and shriveling than the control. UV exposure also reduced decay, tissue damage, and electrolyte leakage. After 12 d at 5 degrees C, UV-C irradiated peppers remained firmer and had higher resistance to deformation than the control. The UV-C treatments also reduced weight loss and pectin solubilization. UV-C exposure decreased the counts of mesophile bacteria and molds, and did not affect acidity or sugars. UV-C treated fruit stored for 0 or 7 d at 5 degrees C did not show major differences in antioxidants from the control as measured against DPPH(*) or ABTS(*)+ radicals. Results suggest that UV-C exposure is useful to maintain quality of refrigerated fresh-cut green pepper. PRACTICAL APPLICATION: Exposure to UV-C radiation before packing and refrigeration could be a useful nonchemical alternative to maintain quality and reduce postharvest losses in the fresh-cut industry. PMID- 22671522 TI - Optimization of enzymatic clarification of green asparagus juice using response surface methodology. AB - Enzymatic clarification conditions for green asparagus juice were optimized by using response surface methodology (RSM). The asparagus juice was treated with pectinase at different temperatures (35 degrees C-45 degrees C), pH values (4.00-5.00), and enzyme concentrations (0.6-1.8 v/v%). The effects of enzymatic treatment on juice clarity and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging capacity were investigated by employing a 3-factor central composite design coupled with RSM. According to response surface analysis, the optimal enzymatic treatment condition was pectinase concentration of 1.45%, incubation temperature of 40.56 degrees C and pH of 4.43. The clarity, juice yield, and soluble solid contents in asparagus juice were significantly increased by enzymatic treatment at the optimal conditions. DPPH radical-scavenging capacity was maintained at the level close to that of raw asparagus juice. These results indicated that enzymatic treatment could be a useful technique for producing green asparagus juice with high clarity and high-antioxidant activity. PRACTICAL APPLICATION: Treatment with 1.45% pectinase at 40.56 degrees C, pH 4.43, significantly increased the clarity and yield of asparagus juice. In addition, enzymatic treatment maintained antioxidant activity. Thus, enzymatic treatment has the potential for industrial asparagus juice clarification. PMID- 22671521 TI - Bioactive compounds in lipid fractions of pumpkin (Cucurbita sp) seeds for use in food. AB - Seeds are considered to be agro-industrial residues, which can be used as source of macronutrients and/or raw material for extraction of vegetable oils, since they present great quantities of bioactive compounds. This study aimed to characterize the lipid fractions and the seeds of pumpkin (Cucurbita sp) varieties Nova Caravela, Mini Paulista, Menina Brasileira, and Moranga de Mesa aiming at using them in food. The chemical composition of the seeds was performed according to the official methods of American Oil Chemists' Society and Association of Official Analytical Chemists. Total carotenoids and phenolic compounds were determined by spectrophotometry, while the levels of tocopherols were analyzed by high efficiency liquid chromatography. It was noted that the seeds contain high amounts of macronutrients that are essential for the functioning of the human organism. As to total carotenoids, Mini Paulista and Menina Brasileira pumpkin varieties presented significant amounts, 26.80 and 26.03 MUg/g, respectively. Mini Paulista and Nova Caravela pumpkin varieties showed high amounts of total phenolic compounds in the lipid fractions and in the seeds. It was also found that gamma-tocopherol is the isomer that stood out in the lipid fractions and in the seeds, mainly in Menina Brasileira. Finally, the consumption of these seeds and use of lipid fractions provide the supply of large quantities of compounds that are beneficial for health and that may be potentially used in food, besides representing an alternative to better use of agro-industrial residues. PRACTICAL APPLICATION: Bioactive compounds, besides presenting basic nutritional functions, provide metabolic and physiological health benefits when consumed as part of the usual diet. Therefore, there is a growing interest in vegetable oils of special composition, such as the ones extracted from fruit seeds. The seeds of Cucurbita sp are shown to be promising sources of oils, and especially the Cucurbita moschata and maxima species have not yet been fully elucidated. For this reason, it becomes important to investigate the chemical composition and lipid fractions of these seeds, aiming to use them in food. PMID- 22671523 TI - Effect of HPMC on the quality of wheat-free bread made from carob germ flour starch mixtures. AB - Carob germ proteins have been shown to have functional properties similar to wheat gluten enabling formulation and production of yeast leavened gluten-free baked goods from a true dough rather than a stiff batter. The purpose of this research was to optimize the production of wheat-free bread containing carob germ flour, corn starch, NaCl, sucrose, hydroxypropyl methylcellulose (HPMC), and H2O. A key criterion was to formulate viscoelastic dough similar to wheat dough. To that end, response surface methodology (RSM) was used to determine optimal levels of carob germ flour, H2O, and HPMC. Components varied as follows: 4.94%-15.05% for carob germ flour, 0.05%-3.75% HPMC, and 65.25%-83.75% H2O (percents are on a flour basis, where carob germ flour in combination with maize starch equals 100%). Sucrose, NaCl, and yeast were held constant at 2%. Bread parameters evaluated were specific volume and crumb hardness, where the largest specific volume and the lowest value for crumb hardness were considered most desirable. The optimum formula as determined by RSM consisted of 7% carob germ flour, 93% maize starch, 2% HPMC, and 80% H2O with predicted crumb hardness of ~200 g of force and a specific volume of ~3.5 cm3/g. When proof time was optimized, a specific volume of ~5.6 ml/g and crumb hardness value of ~156 g of force was observed. Carob germ flour may be used as an alternative to wheat flour in formulating viscoelastic dough and high quality gluten-free bread. PRACTICAL APPLICATION: Celiac disease affects approximately 1% of the world's population. Sufferers of the disease must consume a gluten-free diet. Currently, gluten-free baked products are made from batters and lack the ability to be made from dough based systems which limits the overall processability and product variety. This research is aimed at the utilization of carob germ protein and its ability to form dough to produce an optimal gluten-free bread formulation. This will help to alleviate problems in processability and product variety associated with gluten free baked goods. PMID- 22671524 TI - Identification and characterization of gamma-irradiated dried Lentinus edodes using ESR, SEM, and FTIR analyses. AB - A detailed electron spin resonance (ESR) analysis for different parts of gamma irradiated (0 to 50 kGy) dried mushroom (Lentinus edodes) was conducted to identify radiation-induced signals. All studied mushroom parts except gills produced strong dose-dependent radiation-induced ESR signals particularly at about g = 2.0076, 20005, and 1.9911 demonstrating the generation of crystalline sugar radicals following irradiation. The intensity of these signals was highest in cap skin samples, followed by the cap core, stem skin, whole mushroom powder, and stem core samples, respectively. ESR-based identification was easily possible at 2 kGy or more using mushroom cap skin or cap core as samples. The radiation induced ESR signals were found sensitive to thermal treatment showing the limitation of ESR-based detection in case of heat-processed samples. Scanning electron microscopy (SEM) showed micro-structural damage upon irradiation resulting decreased percentage of rehydration; however, no major alteration was observed through the Fourier transform infrared (FTIR) spectra. Irradiation changed the structural morphology; however, the main functional groups were stable against radiation treatment. PRACTICAL APPLICATION: Food irradiation can confirm hygienic quality and prolong the product shelf life. However, due to lack of international consensus, effective identification methods and detailed quality characterization are required for the general use of this technology. PMID- 22671525 TI - Polyphenol composition and antioxidant activity of cumin (Cuminum cyminum L.) seed extract under drought. AB - This research evaluated the effect of drought on total and individual polyphenol contents as well as the antioxidant activities of cumin (Cuminum cyminum L.) seeds of 2 geographic origins, Tunisia (TCS) and India (ICS). Plants were treated with different levels of water deficit: control. Our results indicated that, in both varieties, moderate water deficit (MWD) improved the number of umbels per plant as well as the number of umbellets per umbel and the seed yield, in comparison to the control, but it decreased under severe water deficit (SWD). Besides, total phenolic contents were higher in the treated seeds and drought increased the level of total and individual polyphenols. This increase was appreciably more important in TCS than in ICS. Moreover, antioxidant activities of the extracts were determined by 4 different test systems, namely 2,2-diphenyl 1-picrylhydrazyl, beta-carotene/linoleic acid chelating, and reducing power assays, and showed that treated seeds exhibited the highest activity, for both TCS and ICS. PMID- 22671526 TI - Increased exposure of vitamin A by Chrysanthemum morifolium Ramat extract in rat was not via induction of CYP1A1, CYP1A2, and CYP2B1. AB - The aim of this study was to investigate the effect of Chrysanthemum morifolium Ramat (CM) extract on the pharmacokinetics of retinol and activities of cytochrome P450s (CYP450s) related to retinoid metabolism. Rats were treated with CM extract for 15 d. Plasma concentrations of retinol were measured following oral administration of retinol (45 mg/kg). Basal levels of retinol and retinoic acid in serum and liver were also measured. 7-Ethoxyresorufin-O-deethylase activity, phenacetin-O-deethylase activity, and 7-pentoxyresorufin-O-deethylase activities were used to assay the activities of CYP1A1, CYP1A2, and CYP2B1 in hepatic microsomes of rats, respectively. Protein expressions of the 3 CYP450s were measured by western blot. Our studies demonstrated that CM extract dose dependently increased basal level of retinol in serum. In pharmacokinetic experiment, CM extract dose-dependently increased plasma concentrations of retinol after oral administration of retinol to rats treated with CM extract. But activities and expressions of CYP1A1, CYP1A2, and CYP2B1 in hepatic microsomes of rats were also induced by CM extract. PMID- 22671527 TI - Effect of flaxseed oil fortified with vitamin E and phytosterols on antioxidant defense capacities and lipids profile in rats. AB - The main proposal of this study was to evaluate in vivo whether flaxseed oils fortified with micronutrients would have beneficial effects on lipid profile and antioxidant status in high-fat fed rats. Male Wistar rats were fed synthetic diets containing 10% of flaxseed oil (FO), phytosterols (PS) fortified FO (PS FO), vitamin E (V(E)) fortified FO (V(E)-FO), V(E) , and PS fortified FO (V(E)-PS FO), respectively, for 4 wk. The results showed that V(E) fortified FO enhanced the enzymatic (SOD and GPX) and nonenzymatic (GSH and V(E)) antioxidant system, lowered the lipid peroxide (TBARS) concentration compared with FO (P < 0.05). And FO fortified with PS significantly reduced the plasma TG, TC and LDL-C levels, and hepatic TG and TC levels of rats compared with FO (P < 0.05), but had no significant effect on antioxidant defense capacities. Combined addition of V(E) and PS in FO had a synergetic effect. These results indicated that flaxseed oils fortified micronutrients V(E) and PS may contribute to reduce the risk factors of cardiovascular disease (CVD) by improving plasma antioxidant defenses and lipids profiles. PRACTICAL APPLICATION: Flaxseed oil usually contains greater than 50% of alpha-linolenic acid (ALA) and is a desire origin for n-3 PUFA. But consuming high dose of n-3 PUFA could lead to oxidative damage through free radical-chain reaction in cellular and subcellular membranes. Our studies showed that a regular intake of V(E) and PS fortified flaxseed oils increased antioxidant defenses and ameliorated lipids profile in high-fat fed rats, and these indicated that the flaxseed oil fortified with these micronutrients might reduce the incidence of CVD. PMID- 22671530 TI - The application of computer color matching techniques to the matching of target colors in a food substrate: a first step in the development of foods with customized appearance. AB - A predictive color matching model based on the colorimetric technique was developed and used to calculate the concentrations of primary food dyes needed in a model food substrate to match a set of standard tile colors. This research is the first stage in the development of novel three-dimensional (3D) foods in which color images or designs can be rapidly reproduced in 3D form. Absorption coefficients were derived for each dye, from a concentration series in the model substrate, a microwave-baked cake. When used in a linear, additive blending model these coefficients were able to predict cake color from selected dye blends to within 3 DeltaE*(ab,10) color difference units, or within the limit of a visually acceptable match. Absorption coefficients were converted to pseudo X10, Y10, and Z10 tri-stimulus values (X10(P), Y10(P), Z10(P)) for colorimetric matching. The Allen algorithm was used to calculate dye concentrations to match the X10(P), Y10(P), and Z10(P) values of each tile color. Several recipes for each color were computed with the tile specular component included or excluded, and tested in the cake. Some tile colors proved out-of-gamut, limited by legal dye concentrations; these were scaled to within legal range. Actual differences suggest reasonable visual matches could be achieved for within-gamut tile colors. The Allen algorithm, with appropriate adjustments of concentration outputs, could provide a sufficiently rapid and accurate calculation tool for 3D color food printing. PRACTICAL APPLICATION: The predictive color matching approach shows potential for use in a novel embodiment of 3D food printing in which a color image or design could be rendered within a food matrix through the selective blending of primary dyes to reproduce each color element. The on-demand nature of this food application requires rapid color outputs which could be provided by the color matching technique, currently used in nonfood industries, rather than by empirical food industry methods. PMID- 22671531 TI - Fast determination of royal jelly freshness by a chromogenic reaction. AB - Royal jelly is one of the most important products of honeybees. Given its role in development of bee brood into fertile individuals of the royal caste it is also used in health products for human consumption. Royal jelly spoils and loses its health-promoting properties depending on storage duration and conditions. To ensure product quality before selling, it is therefore necessary to assess royal jelly freshness. Many indexes of freshness have been suggested, but they all lack reliability or require complex and time-consuming analyses. Here we describe a method to detect royal jelly freshness based on a chromogenic reaction between royal jelly and HCl. We demonstrate that analyses based on color parameters allow for the discrimination of royal jelly samples based on the duration of their storage. Color parameters of royal jelly stored at -18 and 4 degrees C for 28 d remained comparable to that of fresh samples, which supports the reliability of the method. The method of freshness determination described is practical, cheap, and fast and can thus be used in real-time when trading royal jelly. PRACTICAL APPLICATION: The method developed can be used to assess royal jelly freshness. It is practical, cheap, and fast and can thus be used in real-time when trading royal jelly. PMID- 22671532 TI - Dried plum products as a substitute for phosphate in chicken marinade. AB - In order to address the growing demand for more natural poultry products, alkaline phosphates commonly used in chicken breast meat marinades were replaced with plum ingredients and evaluated. For initial sensory evaluation, 200 consumers of chicken were served a small portion of the chicken breast on a plate and were asked to evaluate the product for overall impression, flavor, and texture on a 9-point hedonic scale with 1 = "dislike extremely" and 9 = "like extremely." Also, a 5-point just-about-right (JAR) scale was used on questions about tenderness, juiciness, overall flavor, and saltiness. Both hedonic and JAR demonstrated that the marinades of plum concentrate and the blend of plum fiber and powder were not distinguishable from the control (P > 0.05). Using two different percentages of fiber/powder blend, two different percentages of concentrate, sodium tripolyphosphate (STPP), and no marinade, measurements were made for marinade per cent pickup, thaw loss, and cook loss. Plum concentrate at 1.1% was most similar to STPP in marinade per cent pickup, thaw loss, drip loss, and cook loss. These results show that plum ingredients can potentially be used as a substitute in standard phosphate marinades. PRACTICAL APPLICATION: Consumers are increasingly demanding more natural foods with less artificial additives. This research presents the results of experiments using dried plum ingredients as a substitute for phosphates commonly used in marinades for chicken. Results indicate that dried plum ingredients may be a suitable substitute for phosphates in marinades. PMID- 22671533 TI - Isolation and identification of an exopolysaccharide-producing lactic acid bacterium strain from Chinese Paocai and biosorption of Pb(II) by its exopolysaccharide. AB - Lactic acid bacteria isolated from various traditional Chinese fermented foods were screened for the production of exopolysaccharides (EPS). The strain 70810 from Chinese Paocai, which was identified as Lactobacillus plantarum (HQ259238) by morphological, physiological, biochemical, and 16S rDNA tests, was selected due to its highest EPS production capability (0.859 g/L) for further study. Biosorption of Pb(II) from aqueous solutions by 70810 EPS was studied with parameters of initial pH, contact time, initial Pb(II) concentration, adsorbent dosage, and temperature, respectively. Maximum adsorption of Pb(II) was observed at pH 5, 30 degrees C, and 6 h, respectively. The adsorption capacity was also found to be dependent upon initial Pb(II) concentration and adsorbent dosage. Surface adsorption of the metal at surface of 70810 EPS was confirmed through scanning electron microscopy. Fourier transform infrared spectroscopy spectra analysis indicated that some functional groups (for example, -OH, COO-, C=O, and NH) of 70810 EPS were involved in Pb(II) biosorption process. PRACTICAL APPLICATION: Lactobacillus plantarum 70810 can be used as a starter culture for the production of some fermented foods (for example, yoghurt or fermented soybean milk) and the production of EPS that can meet consumer's demand for products with low levels of additives. The EPS may be used as a potential biosorbent for the removal of heavy metal from environment and these fermented foods maybe have the potential effect to excrete lead from human body. PMID- 22671535 TI - Living with hereditary haemorrhagic telangiectasia: coping and psychological distress - a cross-sectional study. AB - PURPOSE: The purpose of this study was to examine the relationship between coping strategies measured by Coping Orientation to Problems Experienced Scale (COPE) and psychological distress measured by Hospital Anxiety and Depression Scale (HADS) and Becks Hopelessness Scale (BHS) in individuals living with Hereditary hemorrhagic telangiectasia (HHT) and to examine if coping strategies might have a mediating role between experienced illness and psychological distress. HHT is mainly caused by mutations in the ENG- or ALK1-genes and associated with a shorter life span. 90% of patients have recurrent nosebleeds. METHOD: 66 individuals affected of HHT participated in this cross-sectional study, completing questions due to demographic variables, Experience of illness, COPE, BHS and HADS. X(2) test, bivariate correlations with Pearson r and hierarchical multiple regression were used using PASW 18. RESULTS: Experience of illness made the highest variance in anxiety, depression and hopelessness and the coping strategy "behavioral disengagement" seems to have a mediating role between nose bleedings, being afraid of complications, satisfied with life and psychological distress. CONCLUSIONS: Experience of illness is of big importance in psychological distress in individuals affected of HHT, and behavioral disengagement explained the actual relationship between experience of illness and psychological distress. PMID- 22671536 TI - Host-parasite interaction and microbiome response: effects of fungal infections on the bacterial community of the Alpine lichen Solorina crocea. AB - The lichen symbiosis allows a self-sustained life under harsh environmental conditions, yet symbiotic integrity can be affected by fungal parasites. Nothing is known about the impact of these biologically diverse and often specific infections on the recently detected bacterial community in lichens. To address this question, we studied the arctic-alpine 'chocolate chip lichen' Solorina crocea, which is frequently infected by Rhagadostoma lichenicola. We sampled healthy and infected lichens at two different sites in the Eastern Alps. High abundances of Acidobacteria, Planctomycetes, and Proteobacteria were identified analyzing 16S rRNA gene regions obtained by barcoded pyrosequencing. At the phylum and genus level, no significant alterations were present among infected and healthy individuals. Yet, evidence for a differentiation of communities emerged, when data were analyzed at the strain level by detrended correspondence analysis. Further, a profile clustering network revealed strain-specific abundance shifts among Acidobacteria and other bacteria. Study of stability and change in host-associated bacterial communities requires a fine-grained analysis at strain level. No correlation with the infection was found by analysis of nifH genes responsible for nitrogen fixation. PMID- 22671537 TI - Bone mass and biochemical markers of bone turnover in children and adolescents with chronic immune thrombocytopenia: relation to corticosteroid therapy and vitamin D receptor gene polymorphisms. AB - Optional drug therapy in refractory chronic immune thrombocytopenia (ITP) includes standard oral, pulsed high-dose steroid therapy, intravenous gamma globulin, anti-D, and immunosuppressive therapy or thrombopoietin receptor agonists. This work aimed to study the bone mass in children and adolescents with chronic ITP in relation to biochemical markers of bone turnover, cumulative steroid therapy, and the possible modulating effect of vitamin D receptor (VDR) gene polymorphisms. Thirty-six children and adolescents with chronic ITP were recruited from the Hematology Clinic, Children's Hospital, Ain Shams University and the Hematology Clinic of the National Research Centre in Egypt and compared with 43 healthy age- and sex-matched controls. The total cumulative dose of steroids was calculated. Bone markers (serum osteocalcin (OC) and propeptide I precollagen (PICP) and urinary deoxypyridinoline (DPD) excretion), analysis of VDR gene distribution, and dual energy X-ray absorptiometry at lumbar and hip regions were performed for patients and controls. Compared to controls, chronic ITP patients had higher body mass index (BMI) and lower height for age standard deviation score (SDS). Chronic ITP patients had lower levels of OC and C-terminal propeptide of type I procollagen (PICP) and higher urinary DPD excretion, and bone mineral density (BMD) was significantly lower for both spine and hip z-score (<0.001). BMD was inversely correlated with urinary DPD excretion, age, BMI, and cumulative steroid dose. There was significant negative correlation between cumulative oral steroid dose and BMD (r = -0.4, P = 0.01 and r = -0.45, p = 0.001 for spine and hip z-scores, respectively), but the correlation was non significant in relation to cumulative pulsed steroid therapy. FokI polymorphism was significantly related to BMD for both spine and hip z-score (p = 0.015 and p = 0.008, respectively), but there was no relation between BMD and Bsm1 polymorphism. FokI gene polymorphism may be one of the contributing factors in bone loss in patients on chronic steroid therapy. High cumulative doses of corticosteroids increased bone resorption in young chronic ITP patients. Longitudinal studies are needed to confirm the effect of different steroid protocols on bone turnover. Protocols of therapy of chronic ITP should restrict corticosteroid use in growing children and favor alternative less harmful therapies. PMID- 22671538 TI - Next-generation studies of mating system evolution. AB - The specificity of mate selection can vary from wantonly indiscriminate to extraordinarily choosy, and depends in large part on molecules expressed on the surfaces of sperm and eggs. Understanding the evolution of this specificity of gamete recognition leads to important insights into the evolution of reproductive isolation and speciation. One productive area of research has focused on genes that encode gamete recognition proteins in broadcast-spawning marine invertebrates. These gene products are relatively accessible to biochemical and cellular analyses of expression and function, and they mediate almost all of the elements of mate selection and specificity between males and females of such species. However, genetic analyses of their evolution are currently limited to a few combinations of molecules and taxa, and may miss the broader view of adaptive responses to selection on mating specificity across many genes and many types of mating systems. A transcriptomic study shows how next-generation sequencing methods and analyses could relatively easily broaden such studies to more clades, deepen those studies to include more of the interacting molecular parts that mediate gamete recognition, and eventually lead to a more complete understanding of the molecular basis for mating system variation and its evolutionary response to selection. PMID- 22671539 TI - The Tegula tango: a coevolutionary dance of interacting, positively selected sperm and egg proteins. AB - Reproductive proteins commonly show signs of rapid divergence driven by positive selection. The mechanisms driving these changes have remained ambiguous in part because interacting male and female proteins have rarely been examined. We isolate an egg protein the vitelline envelope receptor for lysin (VERL) from Tegula, a genus of free-spawning marine snails. Like VERL from abalone, Tegula VERL is a major component of the VE surrounding the egg, includes a conserved zona pellucida (ZP) domain at its C-terminus, and possesses a unique, negatively charged domain of about 150 amino acids implicated in interactions with the positively charged lysin. Unlike for abalone VERL, where this unique VERL domain occurs in a tandem array of 22 repeats, Tegula VERL has just one such domain. Interspecific comparisons show that both lysin and the VERL domain diverge via positive selection, whereas the ZP domain evolves neutrally. Rates of nonsynonymous substitution are correlated between lysin and the VERL domain, consistent with sexual antagonism, although lineage-specific effects, perhaps owing to different ecologies, may alter the relative evolutionary rates of sperm- and egg-borne proteins. PMID- 22671540 TI - Natural hybridization in the sea urchin genus Pseudoboletia between species without apparent barriers to gamete recognition. AB - Marine species with high dispersal potential often have huge ranges and minimal population structure. Combined with the paucity of geographic barriers in the oceans, this pattern raises the question as to how speciation occurs in the sea. Over the past 20 years, evidence has accumulated that marine speciation is often linked to the evolution of gamete recognition proteins. Rapid evolution of gamete recognition proteins in gastropods, bivalves, and sea urchins is correlated with gamete incompatibility and contributes to the maintenance of species boundaries between sympatric congeners. Here, we present a counterexample to this general pattern. The sea urchins Pseudoboletia indiana and P. maculata have broad ranges that overlap in the Indian and Pacific oceans. Cytochrome oxidase I sequences indicated that these species are distinct, and their 7.3% divergence suggests that they diverged at least 2 mya. Despite this, we suspected hybridization between them based on the presence of morphologically intermediate individuals in sympatric populations at Sydney, Australia. We assessed the opportunity for hybridization between the two species and found that (1) individuals of the two species occur within a meter of each other in nature, (2) they have overlapping annual reproductive cycles, and (3) their gametes cross-fertilize readily in the laboratory and in the field. We genotyped individuals with intermediate morphology and confirmed that many were hybrids. Hybrids were fertile, and some female hybrids had egg sizes intermediate between the two parental species. Consistent with their high level of gamete compatibility, there is minimal divergence between P. indiana and P. maculata in the gamete recognition protein bindin, with a single fixed amino acid difference between the two species. Pseudoboletia thus provides a well-characterized exception to the idea that broadcast spawning marine species living in sympatry develop and maintain species boundaries through the divergence of gamete recognition proteins and the associated evolution of gamete incompatibility. PMID- 22671541 TI - Low rates of bindin codon evolution in lecithotrophic Heliocidaris sea urchins. AB - Life-history variables including egg size affect the evolutionary response to sexual selection in broadcast-spawning sea urchins and other marine animals. Such responses include high or low rates of codon evolution at gamete recognition loci that encode sperm- and egg-surface peptides. Strong positive selection on such loci affects intraspecific mating success and interspecific reproductive divergence (and may play a role in speciation). Here, we analyze adaptive codon evolution in the sperm acrosomal protein bindin from a brooding sea urchin (Heliocidaris bajulus, with large eggs and nonfeeding or lecithotrophic larval development) and compare our results to previously published data for two closely related congeners. Purifying selection and low relative rates of bindin nonsynonymous substitution in H. bajulus were significantly different from selectively neutral bindin evolution in H. erythrogramma despite similar large egg size in those two species, but were similar to the background rate of nonsynonymous bindin substitution for other closely related sea urchins (including H. tuberculata, all with small egg size and feeding planktonic larval development). Bindin evolution is not driven by egg size variation among Heliocidaris species, but may be more consistent with an alternative mechanism based on the effects of high or low spatial density of conspecific mates. PMID- 22671542 TI - Contemporary evolution of sea urchin gamete-recognition proteins: experimental evidence of density-dependent gamete performance predicts shifts in allele frequencies over time. AB - Species whose reproductive strategies evolved at one density regime might be poorly adapted to other regimes. Field and laboratory experiments on the sea urchin Strongylocentrotus franciscanus examined the influences of the two most common sperm-bindin alleles, which differ at two amino acid sites, on fertilization success. In the field experiment, the arginine/glycine (RG) genotype performed best at low densities and the glycine/arginine (GR) genotype at high densities. In the laboratory experiment, the RG genotype had a higher affinity with available eggs, whereas the GR genotype was less likely to induce polyspermy. These sea urchins can reach 200 years of age. The RG allele dominates in larger/old sea urchins, whereas smaller/younger sea urchins have near-equal RG and GR allele frequencies. A latitudinal cline in RG and GR genotypes is consistent with longer survival of sea urchins in the north and with predominance of RG genotypes in older individuals. The largest/oldest sea urchins were likely conceived at low densities, before sea-urchin predators, such as sea otters, were overharvested and sea-urchin densities exploded off the west coast of North America. Contemporary evolution of gamete-recognition proteins might allow species to adapt to shifts in abundances and reduces the risk of reproductive failure in altered populations. PMID- 22671543 TI - Scale-specific sex-biased dispersal in the Valais shrew unveiled by genetic variation on the Y chromosome, autosomes, and mitochondrial DNA. AB - We investigated sex specificities in the evolutionary processes shaping Y chromosome, autosomes, and mitochondrial DNA patterns of genetic structure in the Valais shrew (Sorex antinorii), a mountain dwelling species with a hierarchical distribution. Both hierarchical analyses of variance and isolation-by-distance analyses revealed patterns of population structure that were not consistent across maternal, paternal, and biparentally inherited markers. Differentiation on a Y microsatellite was lower than expected from the comparison with autosomal microsatellites and mtDNA, and it was mostly due to genetic variance among populations within valleys, whereas the opposite was observed on other markers. In addition, there was no pattern of isolation by distance for the Y, whereas there was strong isolation by distance on mtDNA and autosomes. We use a hierarchical island model of coancestry dynamics to discuss the relative roles of the microevolutionary forces that may induce such patterns. We conclude that sex biased dispersal is the most important driver of the observed genetic structure, but with an intriguing twist: it seems that dispersal is strongly male biased at large spatial scale, whereas it is mildly biased in favor of females at local scale. These results add to recent reports of scale-specific sex-biased dispersal patterns, and emphasize the usefulness of the Y chromosome in conjunction with mtDNA and autosomes to infer sex specificities. PMID- 22671544 TI - Lineage-specific variation in slow- and fast-X evolution in primates. AB - Theories predict that the evolutionary rates of X-linked regions can differ from those of autosomal regions. The male-biased mutation theory predicts a slower rate of neutral substitution on the X chromosome (slow-X evolution), as the X spends less time in male germlines, where more mutations originate per generation than in female germlines. The fast-X theory, however, predicts a faster rate of adaptive substitution on the X chromosome when newly arising beneficial mutations are, on average, partially recessive (fast-X evolution), as the X enjoys a greater efficacy of positive selection. The slow- and fast-X processes are expected to interact as the degree of male-biased mutation can in turn influence the relative rate of adaptive evolution on the X. Here, we investigate lineage specific variation in, and the interaction of, slow- and fast-X processes using genomic data from four primates. We find consistent evidence for slow-X evolution in all lineages. In contrast, evidence for fast-X evolution exists in only a subset of lineages. In particular, the marmoset lineage, which shows the strongest evidence of fast-X, exhibits the lowest male mutation bias. We discuss the possible interaction between slow- and fast-X evolution and other factors that influence the degrees of slow- and fast-X evolution. PMID- 22671545 TI - Heritability of preferences for multiple cues of mate quality in humans. AB - Human mate preferences have received a great deal of attention in recent decades because of their centrality to sexual selection, which is thought to play a substantial role in human evolution. Most of this attention has been on universal aspects of mate preferences, but variation between individuals is less understood. In particular, the relative contribution of genetic and environmental influences to variation in mate preferences is key to sexual selection models but has barely been investigated in humans, and results have been mixed in other species. Here, we used data from over 4000 mostly female twins who ranked the importance of 13 key traits in a potential partner. We used the classical twin design to partition variation in these preferences into that due to genes, family environment, and residual factors. In women, there was significant variability in the broad-sense heritability of individual trait preferences, with physical attractiveness the most heritable (29%) and housekeeping ability the least (5%). Over all the trait preferences combined, broad-sense heritabilities were highly significant in women and marginally significant in men, accounting for 20% and 19% of the variation, respectively; family environmental influences were much smaller. Heritability was a little higher in reproductive aged than in nonreproductive aged women, but the difference was not significant. PMID- 22671546 TI - Joint reconstruction of divergence times and life-history evolution in placental mammals using a phylogenetic covariance model. AB - Violation of the molecular clock has been amply documented, and is now routinely taken into account by molecular dating methods. Comparative analyses have revealed a systematic component in rate variation, relating it to the evolution of life-history traits, such as body size or generation time. Life-history evolution can be reconstructed using Brownian models. However, the resulting estimates are typically uncertain, and potentially sensitive to the underlying assumptions. As a way of obtaining more accurate ancestral trait and divergence time reconstructions, correlations between life-history traits and substitution rates could be used as an additional source of information. In this direction, a Bayesian framework for jointly reconstructing rates, traits, and dates was previously introduced. Here, we apply this model to a 17 protein-coding gene alignment for 73 placental taxa. Our analysis indicates that the coupling between molecules and life history can lead to a reevaluation of ancestral life-history profiles, in particular for groups displaying convergent evolution in body size. However, reconstructions are sensitive to fossil calibrations and to the Brownian assumption. Altogether, our analysis suggests that further integrating inference of rates and traits might be particularly useful for neontological macroevolutionary comparative studies. PMID- 22671547 TI - Early evolutionary trends in ammonoid embryonic development. AB - During the Devonian Nekton Revolution, ammonoids show a progressive coiling of their shell just like many other pelagic mollusk groups. These now extinct, externally shelled cephalopods derived from bactritoid cephalopods with a straight shell in the Early Devonian. During the Devonian, evolutionary trends toward tighter coiling and a size reduction occurred in ammonoid embryonic shells. In at least three lineages, descendants with a closed umbilicus evolved convergently from forms with an opening in the first whorl (umbilical window). Other lineages having representatives with open umbilici became extinct around important Devonian events whereas only those with more tightly coiled embryonic shells survived. This change was accompanied by an evolutionary trend in shape of the initial chamber, but no clear trend in its size. The fact that several ammonoid lineages independently reduced and closed the umbilical window more or less synchronously indicates that common driving factors were involved. A trend in size decrease of the embryos as well as the concurrent increase in adult size in some lineages likely reflects a fundamental change in reproductive strategies toward a higher fecundity early in the evolutionary history of ammonoids. This might have played an important role in their subsequent success as well as in their demise. PMID- 22671548 TI - Rates of morphological evolution are correlated with species richness in salamanders. AB - The tempo and mode of species diversification and phenotypic evolution vary widely across the tree of life, yet the relationship between these processes is poorly known. Previous tests of the relationship between rates of phenotypic evolution and rates of species diversification have assumed that species richness increases continuously through time. If this assumption is violated, simple phylogenetic estimates of net diversification rate may bear no relationship to processes that influence the distribution of species richness among clades. Here, we demonstrate that the variation in species richness among plethodontid salamander clades is unlikely to have resulted from simple time-dependent processes, leading to fundamentally different conclusions about the relationship between rates of phenotypic evolution and species diversification. Morphological evolutionary rates of both size and shape evolution are correlated with clade species richness, but are uncorrelated with simple estimators of net diversification that assume constancy of rates through time. This coupling between species diversification and phenotypic evolution is consistent with the hypothesis that clades with high rates of morphological trait evolution may diversify more than clades with low rates. Our results indicate that assumptions about underlying processes of diversity regulation have important consequences for interpreting macroevolutionary patterns. PMID- 22671549 TI - Intraguild predation drives evolutionary niche shift in threespine stickleback. AB - Intraguild predation--competition and predation by the same antagonist--is widespread, but its evolutionary consequences are unknown. Intraguild prey may evolve antipredator defenses, superior competitive ability on shared resources, or the ability to use an alternative resource, any of which may alter the structure of the food web. We tested for evolutionary responses by threespine stickleback to a benthic intraguild predator, prickly sculpin. We used a comparative morphometric analysis to show that stickleback sympatric with sculpin are more armored and have more limnetic-like body shapes than allopatric stickleback. To test the ecological implications of this shift, we conducted a mesocosm experiment that varied sculpin presence and stickleback population of origin (from one sympatric and one allopatric lake). Predation by sculpin greatly increased the mortality of allopatric stickleback. In contrast, sculpin presence did not affect the mortality of sympatric stickleback, although they did have lower growth rates suggesting increased nonpredatory effects of sculpin. Consistent with their morphology, sympatric stickleback included more pelagic prey in their diets, leading to depletion of zooplankton in the mesocosms. These findings suggest that intraguild prey evolution has altered food web structure by reducing both predation by the intraguild predator and diet overlap between species. PMID- 22671550 TI - Phylogenetic analyses unravel the evolutionary history of NAC proteins in plants. AB - NAC (NAM/ATAF/CUC) proteins are one of the largest groups of transcription factors in plants. Although many NAC proteins based on Arabidopsis and rice genomes have been reported in a number of species, a complete survey and classification of all NAC genes in plant species from disparate evolutionary groups is lacking. In this study, we analyzed whole-genome sequences from nine major lineages of land plants to unveil the relationships between these proteins. Our results show that there are fewer than 30 NAC proteins present in both mosses and lycophytes, whereas more than 100 were found in most of the angiosperms. Phylogenetic analyses suggest that NAC proteins consist of 21 subfamilies, most of which have highly conserved non-NAC domain motifs. Six of these subfamilies existed in early-diverged land plants, whereas the remainder diverged only within the angiosperms. We hypothesize that NAC proteins probably originated sometime more than 400 million years ago and expanded together with the differentiation of plants into organisms of increasing complexity possibly after the divergence of lycophytes from the other vascular plants. PMID- 22671551 TI - Phylogeny of Leavenworthia S-alleles suggests unidirectional mating system evolution and enhanced positive selection following an ancient population bottleneck. AB - The adoption of self-fertilization from an ancestral outcrossing state is one of the most common evolutionary transitions in the flowering plants. In the mustard family, outcrossing is typically enforced by sporophytic self-incompatibility (SI), but there are also many self-compatible species. The genus Leavenworthia contains taxa that either possess or lack SI. Here, we present data showing that SI is associated with strict outcrossing and that there is widespread trans specific sequence polymorphism at the locus involved in the recognition of self pollen (the S-locus). This ancestral polymorphism is consistent with the presence of an outcrossing mating system in the common ancestor of Leavenworthia species, and suggests that there have been several independent losses of SI in the group. When compared with other mustard species, the bulk of Leavenworthia S-allele sequences are highly diverged from those found in other Brassicaceae and show relatively low levels of nucleotide diversity, a pattern that suggests the common ancestor of the genus likely underwent a strong population bottleneck. The hypothesis of postbottleneck S-locus rediversification is supported by tests showing stronger positive selection acting on S-alleles from Leavenworthia than those found in other Brassicaceae. PMID- 22671552 TI - Concerted versus independent evolution and the search for multiple refugia: comparative phylogeography of four forest beetles. AB - Phylogeographic structure and its underlying causes are not necessarily shared among community members, with important implications for using individual organisms as indicators for ecosystem evolution, such as the identification of forest refugia. We used mitochondrial DNA (cox1), Bayesian coalescent ancestral state reconstruction (implemented in BEAST), and ecological niche models (ENMs) to construct geospatial histories for four codistributed New Zealand forest beetles (Leiodidae, Nitidulidae, Staphylinidae, and Zopheridae) to examine the extent to which they have tracked environmental changes together through time. Hindcast ENMs identified potential forest refugia during the Last Glacial Maximum, whereas ancestral state reconstruction identified key geographic connections for each species, facilitating direct comparison of dispersal patterns supported by the data and the time frame in which they occurred. Well supported geographic state transitions for each species were mostly between neighboring regions, favoring a historical scenario of stepping stone colonization of newly suitable habitat rather than long distance dispersal. No geographic state transitions were shared by all four species, but three shared multiple projected South Island refugia and recent dispersal from the southernmost refugium. In contrast, strongly supported dispersal patterns in the refugia-rich northern South Island suggest more individualistic responses to environmental change in these ecologically similar forest species. PMID- 22671553 TI - Deep under the sea: unraveling the evolutionary history of the deep-sea squat lobster Paramunida (Decapoda, Munididae). AB - The diversification of Indo-Pacific marine fauna has long captivated the attention of evolutionary biologists. Previous studies have mainly focused on coral reef or shallow water-associated taxa. Here, we present the first attempt to reconstruct the evolutionary history--phylogeny, diversification, and biogeography--of a deep-water lineage. We sequenced the molecular markers 16S, COI, ND1, 18S, and 28S for nearly 80% of the nominal species of the squat lobster genus Paramunida. Analyses of the molecular phylogeny revealed an accelerated diversification in the late Oligocene-Miocene followed by a slowdown in the rate of lineage accumulation over time. A parametric biogeographical reconstruction showed the importance of the southwest Pacific area, specifically the island arc of Fiji, Tonga, Vanuatu, Wallis, and Futuna, for diversification of squat lobsters, probably associated with the global warming, high tectonic activity, and changes in oceanic currents that took place in this region during the Oligocene-Miocene period. These results add strong evidence to the hypothesis that the Neogene was a period of major diversification for marine organisms in both shallow and deep waters. PMID- 22671554 TI - Maintenance and loss of heterozygosity in a thelytokous lineage of honey bees (Apis mellifera capensis). AB - An asexual lineage that reproduces by automictic thelytokous parthenogenesis has a problem: rapid loss of heterozygosity resulting in effective inbreeding. Thus, the circumstances under which rare asexual lineages thrive provide insights into the trade-offs that shape the evolution of alternative reproductive strategies across taxa. A socially parasitic lineage of the Cape honey bee, Apis mellifera capensis, provides an example of a thelytokous lineage that has endured for over two decades. It has been proposed that cytological adaptations slow the loss of heterozygosity in this lineage. However, we show that heterozygosity at the complementary sex determining (csd) locus is maintained via selection against homozygous diploid males that arise from recombination. Further, because zygosity is correlated across the genome, it appears that selection against diploid males reduces loss of homozygosity at other loci. Selection against homozygotes at csd results in substantial genetic load, so that if a thelytokous lineage is to endure, unusual ecological circumstances must exist in which asexuality permits such a high degree of fecundity that the genetic load can be tolerated. Without these ecological circumstances, sex will triumph over asexuality. In A. m. capensis, these conditions are provided by the parasitic interaction with its conspecific host, Apis mellifera scutellata. PMID- 22671555 TI - Wolbachia infection and dramatic intraspecific mitochondrial DNA divergence in a fig wasp. AB - Mitochondria and Wolbachia are maternally inherited genomes that exhibit strong linkage disequilibrium in many organisms. We surveyed Wolbachia infections in 187 specimens of the fig wasp species, Ceratosolen solmsi, and found an infection prevalence of 89.3%. DNA sequencing of 20 individuals each from Wolbachia infected and -uninfected subpopulations revealed extreme mtDNA divergence (up to 9.2% and 15.3% in CO1 and cytochrome b, respectively) between infected and uninfected wasps. Further, mtDNA diversity was significantly reduced within the infected group. Our sequencing of a large part of the mitochondrial genome from both Wolbachia-infected and -uninfected individuals revealed that high sequence divergence is common throughout the mitochondrial genome. These patterns suggest a partial selective sweep of mitochondria subsequent to the introduction of Wolbachia into C. solsmi, by hybrid introgression from a related species. PMID- 22671556 TI - Sibling competition arena: selfing and a competition arena can combine to constitute a barrier to gene flow in sympatry. AB - Closely related species coexisting in sympatry provide critical insight into the mechanisms underlying speciation and the maintenance of genetic divergence. Selfing may promote reproductive isolation by facilitating local adaptation, causing reduced hybrid fitness in parental environments. Here, we propose a novel mechanism by which selfing can further impair interspecific gene flow: selfing may act to ensure that nonhybrid progeny systematically co-occur whenever hybrid genotypes are produced. Under a competition arena, the fitness differentials between nonhybrid and hybrid progeny are then magnified, preventing development of interspecific hybrids. We investigate whether this "sibling competition arena" can explain the coexistence in sympatry of closely related species of the plant fungal pathogens (Microbotryum) causing anther-smut disease. The probabilities of intrapromycelial mating (automixis), outcrossing, and sibling competition were manipulated in artificial inoculations to evaluate their contribution to reproductive isolation. We report that both intrapromycelial selfing and sibling competition significantly reduced rates of hybrid infection beyond that expected based solely upon selfing rates and noncompetitive fitness differentials between hybrid and nonhybrid progeny. Our results thus suggest that selfing and a sibling competition arena can combine to constitute a barrier to gene flow and diminish selection for additional barriers to gene flow in sympatry. PMID- 22671557 TI - Population subdivision and adaptation in asexual populations of Saccharomyces cerevisiae. AB - Population subdivision limits competition between individuals, which can have a profound effect on adaptation. Subdivided populations maintain more genetic diversity at any given time compared to well-mixed populations, and thus "explore" larger parts of the genotype space. At the same time, beneficial mutations take longer to spread in such populations, and thus subdivided populations do not "exploit" discovered mutations as efficiently as well-mixed populations. Whether subdivision inhibits or promotes adaptation in a given environment depends on the relative importance of exploration versus exploitation, which in turn depends on the structure of epistasis among beneficial mutations. Here we investigate the relative importance of exploration versus exploitation for adaptation by evolving 976 independent asexual populations of budding yeast with several degrees of geographic subdivision. We find that subdivision systematically inhibits adaptation: even the luckiest demes in subdivided populations on average fail to discover genotypes that are fitter than those discovered by well-mixed populations. Thus, exploitation of discovered mutations is more important for adaptation in our system than a thorough exploration of the mutational neighborhood, and increasing subdivision slows adaptation. PMID- 22671558 TI - Genetic erosion in wild populations makes resistance to a pathogen more costly. AB - Populations that have suffered from genetic erosion are expected to exhibit reduced average trait values or decreased variation in adaptive traits when experiencing periodic or emergent stressors such as infectious disease. Genetic erosion may consequentially modify the ability of a potential host population to cope with infectious disease emergence. We experimentally investigate this relationship between genetic variability and host response to exposure to an infectious agent both in terms of susceptibility to infection and indirect parasite-mediated responses that also impact fitness. We hypothesized that the deleterious consequences of exposure to the pathogen (Batrachochytrium dendrobatidis) would be more severe for tadpoles descended from European treefrog (Hyla arborea) populations lacking genetic variability. Although all exposed tadpoles lacked detectable infection, we detected this relationship for some indirect host responses, predominantly in genetically depleted animals, as well as an interaction between genetic variability and pathogen dose on life span during the postmetamorphic period. Lack of infection and a decreased mass and postmetamorphic life span in low genetic diversity tadpoles lead us to conclude that genetic erosion, while not affecting the ability to mount effective resistance strategies, also erodes the capacity to invest in resistance, increased tadpole growth rate, and metamorphosis relatively simultaneously. PMID- 22671559 TI - Resource and competitive dynamics shape the benefits of public goods cooperation in a plant pathogen. AB - Cooperative benefits depend on a variety of ecological factors. Many cooperative bacteria increase the population size of their groups by making a public good available. Increased local population size can alleviate the constraints of kin competition on the evolution of cooperation by enhancing the between-group fitness of cooperators. The cooperative pathogenesis of Agrobacterium tumefaciens causes infected plants to exude opines--resources that provide a nearly exclusive source of nutrient for the pathogen. We experimentally demonstrate that opines provide cooperative A. tumefaciens cells a within-group fitness advantage over saprophytic agrobacteria. Our results are congruent with a resource-consumer competition model, which predicts that cooperative, virulent agrobacteria are at a competitive disadvantage when opines are unavailable, but have an advantage when opines are available at sufficient levels. This model also predicts that freeloading agrobacteria that catabolize opines but cannot infect plants competitively displace the cooperative pathogen from all environments. However, we show that these cooperative public goods also promote increased local population size. A model built from the Price Equation shows that this effect on group size can contribute to the persistence of cooperative pathogenesis despite inherent kin competition for the benefits of pathogenesis. PMID- 22671560 TI - An evaluation of the possible adaptive function of fungal brood covering by Attine ants. AB - Fungus-growing ants (Myrmicinae: Attini) live in an obligate symbiotic relationship with a fungus that they rear for food, but they can also use the fungal mycelium to cover their brood. We surveyed colonies from 20 species of fungus-growing ants and show that brood-covering behavior occurs in most species, but to varying degrees, and appears to have evolved shortly after the origin of fungus farming, but was partly or entirely abandoned in some genera. To understand the evolution of the trait we used quantitative phylogenetic analyses to test whether brood-covering behavior covaries among attine ant clades and with two hygienic traits that reduce risk of disease: mycelial brood cover did not correlate with mutualistic bacteria that the ants culture on their cuticles for their antibiotics, but there was a negative relationship between metapleural gland grooming and mycelial cover. A broader comparative survey showed that the pupae of many ant species have protective cocoons but that those in the subfamily Myrmicinae do not. We therefore evaluated the previously proposed hypothesis that mycelial covering of attine ant brood evolved to provide cocoon-like protection for the brood. PMID- 22671561 TI - In a variable thermal environment selection favors greater plasticity of cell membranes in Drosophila melanogaster. AB - Theory predicts that developmental plasticity, the capacity to change phenotypic trajectory during development, should evolve when the environment varies sufficiently among generations, owing to temporal (e.g., seasonal) variation or to migration among environments. We characterized the levels of cellular plasticity during development in populations of Drosophila melanogaster experimentally evolved for over three years in either constant or temporally variable thermal environments. We used two measures of the lipid composition of cell membranes as indices of physiological plasticity (a.k.a. acclimation): (1) change in the ratio of phosphatidylethanolamine (PE) to phosphatidylcholine (PC) and (2) change in lipid saturation (number of double bonds) in cool (16 degrees C) relative to warm (25 degrees C) developmental conditions. Flies evolved under variable environments had a greater capacity to acclimate the PE/PC ratio compared to flies evolved in constant environments, supporting the prediction that environments with high among-generation variance favor greater developmental plasticity. Our results are consistent with the selective advantage of a more environmentally sensitive allele that may have associated costs in constant environments. PMID- 22671562 TI - The effect of a competitor on a model adaptive radiation. AB - The ecological forces shaping adaptive radiations are of great interest to evolutionary ecologists. Here, we experimentally test the hypothesis that the diversification of a lineage should be limited in the presence of competition from another taxon. We do this by studying a model microbial adaptive radiation (the generation of phenotypic diversity in asexual lineages of the bacterium Pseudomonas fluorescens) in the presence or absence of a competitor (Pseudomonas putida). In a spatially heterogeneous environment, the competitor P. putida reduced P. fluorescens population size only slightly and had no effect on diversification. In a spatially homogeneous environment, the competitor reduced P. fuoresecens population size to a much greater extent. Again the final extent of diversification in P. fluorescens was not affected by the competitor, but early diversification was accelerated. In this environment, P. putida suppressed the growth of a common variant of P. fluorescens and directly or indirectly facilitated the growth of a rare morph. Our results suggest that competition experienced by diversifying lineages may have complex effects on adaptive radiations not fully captured by current theory. PMID- 22671563 TI - Evolution and medicine in undergraduate education: a prescription for all biology students. AB - The interface between evolutionary biology and the biomedical sciences promises to advance understanding of the origins of genetic and infectious diseases in humans, potentially leading to improved medical diagnostics, therapies, and public health practices. The biomedical sciences also provide unparalleled examples for evolutionary biologists to explore. However, gaps persist between evolution and medicine, for historical reasons and because they are often perceived as having disparate goals. Evolutionary biologists have a role in building a bridge between the disciplines by presenting evolutionary biology in the context of human health and medical practice to undergraduates, including premedical and preprofessional students. We suggest that students will find medical examples of evolution engaging. By making the connections between evolution and medicine clear at the undergraduate level, the stage is set for future health providers and biomedical scientists to work productively in this synthetic area. Here, we frame key evolutionary concepts in terms of human health, so that biomedical examples may be more easily incorporated into evolution courses or more specialized courses on evolutionary medicine. Our goal is to aid in building the scientific foundation in evolutionary biology for all students, and to encourage evolutionary biologists to join in the integration of evolution and medicine. PMID- 22671564 TI - Rhodium-catalyzed asymmetric formal cycloadditions of racemic butadiene monoxide with imines. AB - A simple chiral sulfur-alkene hybrid ligand has proven to be highly effective for rhodium-catalyzed formal cycloaddition reactions of racemic butadiene monoxide and imines to furnish spirooxindole oxazolidines or 1,3-oxazolidines with high yields and stereoselectivities. A possible dynamic kinetic resolution as well as a kinetic resolution is considered to be involved in this catalytic process. PMID- 22671565 TI - Detection of a novel HLA-A allele, designated A*02:334. AB - We report a novel allele HLA-A*02:334 with the transition G->A at nucleotide position 282. PMID- 22671566 TI - Effects of breathing on multijoint control of center of mass position during upright stance. AB - Breathing exerts destabilizing effects on postural stability during quiet stance. The authors conducted an experiment to evaluate the role of motor abundance in the organization of the postural synergy compensating for the effects of breathing. They measured the kinematic pattern of covariation among the major joints of the postural chain (ankle, knee, hip, trunk, and neck) as a function of different breathing modes (spontaneous, paced, and increased volume) and different stance instructions (still vs. relaxed) using the uncontrolled manifold approach. Joint variability was structured to preserve the stable position of the center of mass. This result supports the hypothesis that motor abundance of the postural chain plays an important role in the flexible compensation for breathing during quiet stance. PMID- 22671568 TI - Positivity impairments: pervasive and impairing (yet nonprominent?) features of social anxiety disorder. PMID- 22671567 TI - Conceptual and linguistic representations of kinds and classes. AB - We investigate the hypothesis that our conceptual systems provide two formally distinct ways of representing categories by investigating the manner in which lexical nominals (e.g., tree, picnic table) and phrasal nominals (e.g., black bird, birds that like rice) are interpreted. Four experiments found that lexical nominals may be mapped onto kind representations, whereas phrasal nominals map onto class representations but not kind representations. Experiment 1 found that phrasal nominals, unlike lexical nominals, are mapped onto categories whose members need not be of a single kind. Experiments 2 and 3 found that categories named by lexical nominals enter into both class inclusion and kind hierarchies and thus support both class inclusion (is a) and kind specification (kind of) relations, whereas phrasal nominals map onto class representations which support only class inclusion relations. Experiment 4 showed that the two types of nominals represent hierarchical relations in different ways. Phrasal nominals (e.g., white bear) are mapped onto classes that have criteria of membership in addition to those specified by the class picked out by the head noun of the phrase (e.g., bear). In contrast, lexical nominals (e.g., polar bear) specify one way to meet the criteria specified by the more general kind concept (e.g., bear). Implications for the language-conceptual system interface, representation of hierarchical relations, lexicalization, and theories of conceptual combination are discussed. PMID- 22671569 TI - SHPS-1 deficiency induces robust neuroprotection against experimental stroke by attenuating oxidative stress. AB - Src homology 2 domain-containing protein tyrosine phosphatase substrate-1 (SHPS 1), also known as Signal-regulatory protein alpha (SIRPalpha) or SIRPA is a transmembrane protein that is predominantly expressed in neurons, dendritic cells, and macrophages. This study was conducted to investigate the role of SHPS 1 in the oxidative stress and brain damage induced by acute focal cerebral ischemia. Wild-type (WT) and SHPS-1 mutant (MT) mice were subjected to middle cerebral artery occlusion (60 min) followed by reperfusion. SHPS-1 MT mice had significantly reduced infarct volumes and improved neurological function after brain ischemia. In addition, neural injury and oxidative stress were inhibited in SHPS-1 MT mice. The mRNA and protein levels of the antioxidant genes nuclear factor-E2-related factor 2 (Nrf2) and heme oxygenase 1 were up-regulated in SHPS 1 MT mice. The SHPS-1 mutation suppressed the phosphorylation of SHP-1 and SHP-2 and increased the phosphorylation of Akt and GSK3beta. These results provide the first demonstration that SHPS-1 plays an important role in the oxidative stress and brain injury induced by acute cerebral ischemia. The activation of Akt signaling and the up-regulation of Nrf2 and heme oxygenase 1 likely account for the protective effects that were observed in the SHPS-1 MT mice. PMID- 22671570 TI - MMP3 and TIMP1 variants contribute to chronic periodontitis and may be implicated in disease progression. AB - AIM: Matrix metalloproteinases (MMPs) play a key role in the tissue destruction characteristic of chronic periodontitis. The purpose of this study was to investigate the association of MMP and TIMP polymorphisms with chronic periodontitis in two populations. MATERIAL AND METHODS: A total of 34 polymorphisms spanning 12 MMP and 2 TIMP genes were genotyped in 401 individuals from Brazil (99 cases with chronic periodontitis and 302 controls), and 274 individuals from the US (70 cases and 204 controls). Individuals were considered cases if presenting at least three teeth exhibiting sites of clinical attachment loss >= 5 mm in two different quadrants. Controls were characterized by absence of clinical attachment loss and no sites with probing depth >3 mm. MMP3 and TIMP1 mRNA expression was evaluated in healthy and diseased periodontal tissues. RESULTS: TIMP1 showed association with chronic periodontitis in the Brazilian population (for rs5906435, p = 0.0004), whereas MMP3 showed association in the US population (for rs679620, p = 0.0003; and rs650108, p = 0.002) and in the Brazilian population (for rs639752, p = 0.005). MMP3 and TIMP1 mRNA expression was significantly higher in diseased tissues when compared to control tissues. CONCLUSIONS: Our results further support a role for variations in MMP3 in chronic periodontitis and report a novel association with TIMP1. These genes may be considered additional candidate genes for chronic periodontitis. PMID- 22671571 TI - Impact of rituximab on treatment outcomes of patients with diffuse large b-cell lymphoma: a population-based analysis. AB - We conducted a multi-institutional population-based analysis of the survival and toxicity associated with the addition of rituximab to chemotherapy for patients with diffuse large B-cell lymphoma (DLBCL), including patients aged >= 80 years, who were excluded from published randomized trials. Using population-based registries in Ontario, we identified 4021 patients who received chemotherapy with or without rituximab (R-CHOP [rituximab with cyclophosphamide, doxorubicin, vincristine and prednisone] or CHOP) for DLBCL between 1996 and 2007, including 397 patients aged >= 80 years. After propensity score matching, the overall survival (OS) and significant toxicities for R-CHOP and CHOP treatment groups were compared. R-CHOP was associated with a significant increase in 5-year OS compared to CHOP alone (62% vs. 54%; hazard of death = 0.78, P = 0.0004). Survival benefit was seen in all age groups, including those aged >= 80 years. Patients treated with rituximab did not have a significant increase in 1-year hospitalization rates for cardiac, pulmonary, gastrointestinal or neurological diagnoses compared to those treated with CHOP alone. The addition of rituximab to CHOP improves survival in the general population of patients with DLBCL and produces early survival benefit for very elderly patients, without any significant increase in the risk of serious toxicity. PMID- 22671572 TI - Hydroxychloroquine-induced hyperpigmentation. PMID- 22671573 TI - Dynamic contrast-enhanced magnetic resonance imaging of the metastatic potential of tumors: a preclinical study of cervical carcinoma and melanoma xenografts. AB - BACKGROUND: Gadolinium diethylene-triamine penta-acetic acid (Gd-DTPA)-based dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has been suggested to be a useful non-invasive method for providing biomarkers for personalized cancer treatment. In this preclinical study, we investigated whether Gd-DTPA based DCE-MRI may have the potential to differentiate between poorly and highly metastatic tumors. MATERIAL AND METHODS: CK-160 cervical carcinoma and V-27 melanoma xenografts were used as tumor models. Fifty-six tumors were imaged, and parametric images of K(trans) (the volume transfer constant of Gd-DTPA) and v(e) (the fractional distribution volume of Gd-DTPA) were produced by pharmacokinetic analysis of the DCE-MRI series. The host mice were examined for lymph node metastases immediately after the DCE-MRI. RESULTS: Highly metastatic tumors showed lower values for median K(trans) than poorly metastatic tumors (p = 0.00033, CK-160; p < 0.00001, V-27). Median v(e) was lower for highly than for poorly metastatic V-27 tumors (p = 0.047), but did not differ significantly between metastatic and non-metastatic CK-160 tumors (p > 0.05). CONCLUSION: This study supports the clinical attempts to establish DCE-MRI as a method for providing biomarkers for tumor aggressiveness and suggests that tumors showing low K(trans) and low ve values may have high probability of lymphogenous metastatic dissemination. PMID- 22671574 TI - A possible association between coeliac disease and development of radiation pneumonitis. PMID- 22671575 TI - Incidence of thromboembolic events in patients with locally advanced rectal cancer receiving neoadjuvant chemoradiotherapy. PMID- 22671576 TI - Dosimetric comparison between VMAT with different dose calculation algorithms and protons for soft-tissue sarcoma radiotherapy. AB - BACKGROUND: To appraise the potential of volumetric modulated arc therapy (VMAT, RapidArc) and proton beams to simultaneously achieve target coverage and enhanced sparing of bone tissue in the treatment of soft-tissue sarcoma with adequate target coverage. MATERIAL AND METHODS: Ten patients presenting with soft-tissue sarcoma of the leg were collected for the study. Dose was prescribed to 66.5 Gy in 25 fractions to the planning target volume (PTV) while significant maximum dose to the bone was constrained to 50 Gy. Plans were optimised according to the RapidArc technique with 6 MV photon beams or for intensity modulated protons. RapidArc photon plans were computed with: 1) AAA; 2) Acuros XB as dose to medium; and 3) Acuros XB as dose to water. RESULTS: All plans acceptably met the criteria of target coverage (V95% >90-95%) and bone sparing (D(1 cm3) <50 Gy). Significantly higher PTV dose homogeneity was found for proton plans. Near-to maximum dose to bone was similar for RapidArc and protons, while volume receiving medium/low dose levels was minimised with protons. Similar results were obtained for the remaining normal tissue. Dose distributions calculated with the dose to water option resulted ~5% higher than corresponding ones computed as dose to medium. CONCLUSION: High plan quality was demonstrated for both VMAT and proton techniques when applied to soft-tissue sarcoma. PMID- 22671577 TI - Inhibition of specific cellular antioxidant pathways increases the sensitivity of neurons to meta-tetrahydroxyphenyl chlorin-mediated photodynamic therapy in a 3D co-culture model. AB - The effect of photodynamic therapy (PDT) on neurons is of critical importance when treating cancers within or adjacent to the nervous system. Neurons show reduced sensitivity to meta-tetrahydroxyphenyl chlorin (mTHPC) mediated PDT, so the aim of this study was to investigate whether neuron sparing is due to endogenous cellular antioxidant activity. Dorsal root ganglion (DRG) neurons and their associated satellite glia were subjected to mTHPC-PDT in a 3D co-culture system following incubation with antioxidant inhibitors: diethyl dithiocarbamate (DDC, SOD-1 inhibitor), 2-methoxyestradiol (2-MeOH(2), SOD-2 inhibitor) and L buthionine sulfoximine (L-BSO, glutathione synthase inhibitor). Sensitivity of each cell type was assessed using a combination of live/dead staining and immunofluorescence. Pretreatment with DDC and with L-BSO significantly increased the sensitivity of neurons to mTHPC-PDT and also affected satellite glial cell viability, whereas 2-MeOE(2) caused only a small increase in neuron sensitivity (not significant). Pretreatment using a combination of DDC and L-BSO caused a near total loss of neuron and glial cell viability in treatment and control conditions. These findings suggest that the SOD-1 and glutathione pathways are likely to be involved in the neuronal sparing associated with mTHPC-PDT. PMID- 22671578 TI - Effect of captopril on infantile haemangiomas: a retrospective case series. AB - The mechanism of action of beta adrenergic blockers in the involution of infantile haemangioma (IH) remains unclear. It has been proposed that the renin angiotensin pathway may play a role. We present a retrospective case series of 17 patients with IH who were treated with oral corticosteroid therapy and developed hypertension requiring treatment with the angiotensin converting enzyme inhibitor, captopril. All patients, with written documentation, demonstrated an improvement in their lesion at the start of oral corticosteroid therapy (n = 14). Captopril alone did not sustain the corticosteroid-induced involution with a documented worsening of infantile haemangioma in seven out of 12 patients (58%). PMID- 22671579 TI - Langmuir balance investigation of superoxide dismutase interactions with mixed lipid monolayers. AB - Higher than theoretical encapsulation efficiencies in liposomes of the cytoplasmic protein, superoxide dismutase (SOD), were previously observed. The high encapsulation of SOD led to the consideration of lipid-protein interactions and the embedding of SOD in the lipid bilayer. Difficulty in other methods such as dynamic scanning calorimetry due to cholesterol obscuring the measurements brought about the interest for a modified Langmuir monolayer relaxation study. A novel method was devised to distinguish between different lipid compositions that formed either a favorable or an unfavorable environment for SOD. Normalized monolayer relaxations with SOD were compared between mixed-lipid compositions containing 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-distearoyl-sn glycero-3-phosphocholine (DSPC), and cholesterol (Chol). Lipid-monolayer relaxation with and without SOD in the subphase was plotted over 30 min to determine if the protein was altering the lipid-monolayer relaxation. The monolayer relaxation with SOD was normalized to the monolayer relaxation without SOD over the 30 min period. The results indicated that lipid length and mole percent of cholesterol were important parameters that must be adjusted in order to support a favorable environment for SOD interaction with the lipid. It was determined that hydrophobic interactions were dominant over electrostatic forces; thus, SOD was embedding into the lipid monolayer. Additionally, this study was correlated to a previous liposome study and proved that lipid-protein interactions were the reason for the higher encapsulation efficiencies. The significance of this method is that it (1) provides a connection between lipid protein interactions observed in monolayers and bilayers and (2) establishes a simple and effective manner to test lipid compositions for lipid-protein interaction that will aid in optimization of liposome encapsulation efficiency. PMID- 22671580 TI - An N-heterocyclic carbene containing a bithiophene backbone: synthesis and coordination chemistry. AB - A new N-heterocyclic carbene (NHC) containing a fused bithiophene backbone has been synthesized along with its silver(I) and BPh(3) complexes. The donor strength of this unique NHC has been determined from the IR stretching frequencies of the isolated NHC-Rh(CO)(2)Cl complex. The photophysical properties of all of the novel compounds have been investigated and are presented. PMID- 22671581 TI - Stepwise association of hydrogen cyanide and acetonitrile with the benzene radical cation: structures and binding energies of (C6H6*+)(HCN)n, n = 1-6, and (C6H6*+)(CH3CN)n, n = 1-4, clusters. AB - Equilibrium thermochemical measurements using the ion mobility drift cell technique have been utilized to investigate the binding energies and entropy changes associated with the stepwise association of HCN and CH(3)CN molecules with the benzene radical cation in the C(6)H(6)(*+)(HCN)(n) and C(6)H(6)(*+)(CH(3)CN)(n) clusters with n = 1-6 and 1-4, respectively. The binding energy of CH(3)CN to the benzene cation (14 kcal/mol) is stronger than that of HCN (9 kcal/mol) mostly due to a stronger ion-dipole interaction because of the large dipole moment of acetonitrile (3.9 D). However, HCN can form hydrogen bonds with the hydrogen atoms of the benzene cation (CH(delta+)...NCH) and linear hydrogen bonding chains involving HCN...HCN interaction. HCN molecules tend to form externally solvated structures with the benzene cation where the ion is hydrogen bonded to the exterior of HCN chains. For the C(6)H(6)(*+)(CH(3)CN)(n) clusters, internally solvated structures are formed where the acetonitrile molecules are directly interacting with the benzene cation through ion-dipole and hydrogen bonding interactions. The lack of formation of higher clusters with n > 4, in contrast to HCN, suggests the formation of a solvent shell at n = 4, which is attributed to steric interactions among the acetonitrile molecules attached to the benzene cation and to the presence of the blocking CH(3) groups, both effects make the addition of more than four acetonitrile molecules less favorable. PMID- 22671582 TI - Primary health care resources for rehabilitation and secondary prevention after myocardial infarction - a questionnaire survey. AB - BACKGROUND: During the first year after a cardiac event, many patients are offered participation in a cardiac rehabilitation programme, after which the patients are often not given the opportunity to continue to attend rehabilitation and secondary prevention programmes. AIM: This study describes the primary health care centres' (PHCC) resources regarding cardiac rehabilitation/secondary prevention programmes for coronary heart disease (CHD) patients in a southern Swedish region. METHOD: A questionnaire containing 26 dichotomous or multiple choice questions was sent to the responsible manager of all 137 public and private PHCCs in Region Skane. Questionnaires from 91 (66%) of the PHCCs were completed and returned. RESULT: Few nurses at the PHCCs had special training regarding CHD (10%), cardiac rehabilitation (8%) or heart failure (32%). Twenty one per cent of the physicians had special training regarding CHD. One third of the PHCCs did not offer long-term secondary prevention programmes, and few (6%) had any routines for offering socio-economic support to CHD patients. Comparison of private and public PHCCs showed that the private centres could not offer a physiotherapist (61 vs. 84%) or dietician (32 vs. 73%; p = 0.03) to the same extension as the public ones. Furthermore, the majority (91%) of PHCCs had no cooperation with patient organizations. CONCLUSIONS: The PHCCs need to improve the strategies and long-term rehabilitation programmes. Furthermore, they need to focus on education programme for the staff. The result revealed that the PHCCs lack resources, strategies and long-term care programmes for CHD patients. PMID- 22671583 TI - Dual thienopyridine low-response to clopidogrel and prasugrel in a patient with STEMI, cardiogenic shock and early stent thrombosis is overcome by ticagrelor. AB - Little is known about the antiplatelet action of the thienopyridines, clopidogrel and prasugrel, as well as the non-thienopyridine, ticagrelor, in patients suffering from ST-elevation myocardial infarction (STEMI) complicated by cardiogenic shock since systematic comparisons of these antiplatelet agents in this devastating condition are limited so far. This is a report of a patient with STEMI undergoing urgent PCI in cardiogenic shock followed by repeated angioplasty after suffering early stent thrombosis (ST) who showed dual thienopyridine treatment failure of clopidogrel and prasugrel, which was successfully overcome by switching the patient to the non-thienopyridine derivative ticagrelor. PMID- 22671584 TI - Perspectives on tight junction research. AB - The tight junction connects neighboring epithelial or endothelial cells. As a general function, it seals the paracellular pathway and thus prevents back leakage of just transported solutes and water. However, not all tight junctions are merely tight: some tight junction proteins build their own transport pathways by forming channels selective for small cations, anions, or water. Two families of tight junction proteins have been identified, claudins (27 members in mammals) and tight junction-associated MARVEL proteins ((TAMPs) occludin, tricellulin, and MarvelD3); an additional, structurally different, junction protein is junction adhesion molecule (JAM). Besides classification by genetic or molecular kinship, classification of tight junction proteins has been suggested according to permeability attributes. Recent studies describe specific cis and trans interactions and manifold physiologic regulations of claudins and TAMPs. In many inflammatory and infectious diseases they are found to be altered, for example, causing adversely increased permeability. Currently, attempts are being made to alter the paracellular barrier for therapeutic interventions or for transiently facilitating drug uptake. This overview concludes with a list of open questions and future topics in tight junction research. PMID- 22671585 TI - Charge-selective claudin channels. AB - Claudins are the main determinants of barrier properties of the tight junction. Many claudins have been shown to act by tightening the paracellular pathway, but several function as paracellular channels. While some depend on the endogenous claudin background of the analyzed cell line, for other claudins, a distinct charge-selectivity has been shown. This paper portrays cation-selective (claudin 2, claudin-10b, claudin-15) and anion-selective (claudin-10a, claudin-17) claudins and claudins with debatable channel properties (claudin-4, claudin-7, claudin-16). It also describes molecular properties determining the observed charge-selectivity and pore properties in general. In leaky tissues, they widely determine overall transport characteristics by providing paracellular ion selective pathways. In small intestine, claudin-2 and claudin-15 replace each other in the developing gut. In kidney proximal tubules, claudin-2, claudin-10, and claudin-17 allow for paracellular reabsorption of sodium, chloride, and water. PMID- 22671586 TI - Claudin-derived peptides are internalized via specific endocytosis pathways. AB - Claudin proteins are involved in the paracellular tightening of epithelia and endothelia. Their internalization, which can be modulated by extracellular stimuli, for example, proinflammatory cytokines, is a prerequisite for the regulation of the paracellular barrier to allow, for instance, cell migration or drug delivery. The internalization of peptide sequences of claudins is completely unknown. Here, we studied the internalization of two peptides, TAMRA-claudin-1 and TAMRA-claudin-5, derivatives of the extracellular loop of claudin-1 and -5, respectively, in either epithelial or endothelial cells. The cellular uptake of the claudin-1 peptide follows the clathrin-mediated endocytosis as indicated by inhibitors and respective tracers for colocalization. In addition, macropinocytosis and caveolae-mediated endocytosis of the peptide was observed. In contrast, the claudin-5 peptide is mainly internalized via the caveolae mediated endocytosis evidenced by the colocalization with respective tracers and vesicle markers, whereas the nonselective macropinocytosis seems to be involved in a less effective manner. In conclusion, the assumption is supported that claudin peptides can be internalized by specific and nonspecific pathways. PMID- 22671587 TI - A phosphorylation hotspot within the occludin C-terminal domain. AB - Tight junctions (TJs) form paracellular barriers defining the permeability characteristics of epithelial and endothelial cell layers in our body. Tetraspanin integral membrane proteins, including occludin, tricellulin, MarvelD3, and a set of claudins, form a network of anastomosing strands bringing the membranes of neighboring cells into close contact. Occludin is assumed to play an important role in the regulation of TJ formation, structure, and function, and is tightly regulated by phosphorylation. We here summarize the role of occludin phosphorylation on assembly/disassembly and function of TJs and specifically focus on a cluster of 11 amino acids in the C-terminal cytoplasmic domain of occludin (Tyr398-Ser408), including highly conserved phosphorylation sites for c-Src, PKCs, and CK2. Phosphorylation by these kinases affects occludin localization, dynamics, and interaction with other TJ proteins. Interestingly, this phosphorylation hotspot is localized in an unstructured region close to the ZO-1 binding site, and a cysteine residue which is involved in intermolecular disulfide-bond formation thus contributing to occludin dimerization. We discuss potential consequences and open questions in respect to the functional role of this phosphorylation hotspot. PMID- 22671588 TI - Determinants contributing to claudin ion channel formation. AB - Pore-forming properties of claudins (Cld) are likely defined by residues of their first extracellular loop (ECL1). Detailed mechanisms are unclear. MDCK cells overexpressing FLAG-Cld-1 wild-type and mutants were characterized by transepithelial resistance (TER) and ion permeability measurements. Replacing ECL1 residues of sealing Cld-1 by corresponding Cld-2 residues we aimed to identify new determinants responsible for sealing and/or pore formation. We found that E48K and S53E substitutions in human Cld-1 strongly reduced TER and increased permeability for Na(+) and Cl(-) . In contrast, K65D, D68S, and other single substitutions showed no significant change of TER and permeability for Na(+) and Cl(-) . Double substitution S53E/K65D did not change TER and ion permeability, whereas S53E/D68S decreased TER, albeit weaker than S53E. Ratio of permeabilities for Na(+) and Cl(-) revealed no clear charge specificity of the pore induced by S53E or S53E/D68S in Cld-1, suggesting that primarily S53 and potentially D68 in Cld-1 are involved in sealing of the paracellular cleft and that charge-unselective pores may be induced by substituting S53E. PMID- 22671589 TI - Lipolysis-stimulated lipoprotein receptor: a novel membrane protein of tricellular tight junctions. AB - Tricellular tight junctions (tTJs) are specialized structural variants of tight junctions that restrict the free diffusion of solutes at the extracellular space of tricellular contacts. Their presence at cell corners, situated in the angles between three adjacent epithelial cells, was identified early by electron microscopy, but despite their potential importance, tTJs have been generally ignored in epithelial cell biology. Tricellulin was the first molecular component of tTJs shown to be involved in their formation and in epithelial barrier function. However, the precise molecular organization and function of tTJs are still largely unknown. Recently, we identified the lipolysis-stimulated lipoprotein receptor (LSR) as a tTJ-associated membrane protein. LSR recruits tricellulin to tTJs, suggesting that the LSR-tricellulin system plays a key role in tTJ formation. In this paper, we summarize the identification and characterization of LSR as a molecular component of tTJs. PMID- 22671590 TI - Overexpression of claudin-5 but not claudin-3 induces formation of trans interaction-dependent multilamellar bodies. AB - Tight junctions (TJs) regulate paracellular barriers and claudins (Cld) form the backbone of TJ strands. To elucidate the molecular mechanism of claudin polymer formation, TJs were reconstituted by claudin transfection of TJ-free HEK293 cells. Therewith, typical TJ stands can be found at cell-cell contacts. In addition, overexpression of Cld5-YFP induces formation of huge intracellular multilamellar bodies. In contrast, Cld3 does not induce similar structures. Inhibition of trans-interaction of Cld5 by Y148A substitution diminished formation of multilamellar bodies. These results demonstrate claudin subtype specific oligomerization. Cld3 and Cld5 localize to the plasma membrane differentially. Phosphorylation at T207 of Cld5 was suggested to participate in regulation of Cld5 internalization. However, prevention of potential phosphorylation by T207A substitution did not increase Cld5 amount in the plasma membrane of transfected cells. Taken together, if carefully evaluated, transfection of claudin constructs in nonpolar cells is a powerful strategy to improve understanding of subcellular targeting and assembly of TJ proteins. PMID- 22671591 TI - Association between segments of zonula occludens proteins: live-cell FRET and mass spectrometric analysis. AB - The tight junction protein ZO-1 (zonula occludens protein 1) has recruiting/scaffolding functions in the junctional complex of epithelial and endothelial cells. Homodimerization was proposed to be crucial for ZO-1 function. Here, we investigated the ability of ZO-1 domains to mediate self-interaction in living cells. We expressed ZO-1 truncation mutants as fusions with derivatives of green fluorescent protein in tight junction-free HEK-293 cells and determined self-association by means of fluorescence resonance energy transfer measurements using live-cell imaging. We show that both an SH3-hinge-GuK fusion protein and the PDZ2 domain self-associate in our test system. The recombinant PDZ2 domain also binds to ZO-1 and ZO-2 in tight junction-forming HT29/B6 cell lysates, as demonstrated by coprecipitation. Both interaction types are of relevance for the function of ZO-1 in the regulation of the junctional complex in polar cells. PMID- 22671592 TI - Dynamic properties of the tight junction barrier. AB - A principal role of tight junctions is to seal the apical intercellular space and limit paracellular flux of ions and molecules. Despite the fact that tight junctions form heavily cross-linked structures, functional studies have fostered the hypothesis that the tight junction barrier is dynamic and defined by opening and closing events. However, it has been impossible to directly measure tight junction barrier function with sufficient resolution to detect such events. Nevertheless, recent electrophysiological and sieving studies have provided tremendous insight into the presence of at least two pathways of trans-tight junction flux: a high-capacity ion-selective "pore" pathway and a low-capacity "leak" pathway that allows the passage of macromolecules. Furthermore, it is now known that the tight junction molecular structure is highly dynamic and that dynamics are correlated with barrier function. Taken together, these data support a dynamic model of tight junction conductance and suggest that regulation of tight junction openings and closings may provide sensitive means of barrier regulation. PMID- 22671593 TI - Regulation of tight junctions in human normal pancreatic duct epithelial cells and cancer cells. AB - To investigate the regulation of tight junction molecules in normal human pancreatic duct epithelial (HPDE) cells and pancreatic cancer cells, we introduced the human telomerase reverse transcriptase (hTERT) gene into HPDE cells in primary culture and compared them to pancreatic cancer cell lines. The hTERT-transfected HPDE cells were positive for PDE markers and expressed claudin 1, claudin-4, claudin-7, and claudin-18, occludin, tricellulin, marvelD3, JAM-A, zonula occludens (ZO)-1, and ZO-2. The tight junction molecules, including claudin-4 and claudin-18 of normal HPDE cells, were in part regulated via a protein kinase C signal pathway by transcriptional control. In addition, claudin 18 in normal HPDE cells and pancreatic cancer cells was markedly induced by a PKC activator, and claudin-18 in pancreatic cancer cells was also modified by DNA methylation. In the marvel family of normal HPDE cells and pancreatic cancer cells, tricellulin was upregulated via a c-Jun N-terminal kinase pathway, and marvelD3 was downregulated during Snail-induced epithelial-mesenchymal transition. PMID- 22671594 TI - The role for protein tyrosine phosphatase nonreceptor type 2 in regulating autophagosome formation. AB - Genome-wide association studies have identified single nucleotide polymorphisms within the gene locus encoding protein tyrosine phosphatase nonreceptor type 2 (PTPN2) as a risk factor for the development of chronic inflammatory diseases, such as inflammatory bowel disease (IBD), type 1 diabetes, and rheumatoid arthritis. IBD is characterized by a breakdown of the intestinal epithelial barrier function leading to an overwhelming and uncontrolled immune response to bacterial antigens. Recent studies demonstrated that PTPN2 regulates cytokine induced signaling pathways, epithelial barrier function, and cytokine secretion in human intestinal cells. Dysfunction of PTPN2 is also associated with impaired autophagosome formation and defective bacterial handling in intestinal cells. All of these cellular functions have been demonstrated to play a crucial role in the pathogenesis of IBD. The genetic variations within the PTPN2 gene may result in altered protein function, thereby essentially contributing to the onset and perpetuation of chronic inflammatory conditions in the intestine. PMID- 22671595 TI - Caveolin binds independently to claudin-2 and occludin. AB - Treatment of epithelial and endothelial cells with proinflammatory cytokines can stimulate tight junction protein endocytosis, with associated loss of physiologic barrier function. In some instances, the endocytic scaffolding protein, caveolin 1, has been implicated in the cytokine-dependent retrieval of the tight junction proteins occludin and claudins. How caveolin-1 interacts with these proteins, however, remains undefined. Using co-immunoprecipitation assays, we found that caveolin-1 separately interacts with claudin-2 and occludin, but not with ZO-1, ZO-2, or claudin-4. Further, we found that the interactions of caveolin-1 with claudin-2 and occludin were not disrupted by cholesterol removal, suggesting that they were not dependent on co-localization to cholesterol-rich lipid rafts. Co immunoprecipitation of caveolin-1 with chimeras between claudin-2 and -4 indicated that the C-terminal cytoplasmic domain of claudin-2 is required for association with caveolin-1; similar analysis showed that the ZO-1 binding region of occludin is not required for its interaction with caveolin-1. The finding that caveolin-1 interacts with claudin-2 and occludin, but not with claudin-4 or ZO-1, suggests a potential mechanism for selective retrieval of tight junction components. PMID- 22671596 TI - Regulation of epithelial barrier function by the inflammatory bowel disease candidate gene, PTPN2. AB - Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) has been identified as an inflammatory bowel disease (IBD) candidate gene. However, the mechanism through which mutations in the PTPN2 gene contribute to the pathogenesis of IBD has not been identified. PTPN2 acts as a negative regulator of signaling induced by the proinflammatory cytokine, interferon-gamma (IFN-gamma). IFN-gamma is known not only to play an important role in the pathogenesis of Crohn's disease (CD), but also to increase permeability of the intestinal epithelial barrier. We have shown that PTPN2 protects epithelial barrier function by restricting the capacity of IFN-gamma to increase epithelial permeability and prevent induction of expression of the pore-forming protein, claudin-2. These data identify an important functional role for PTPN2 as a protector of the intestinal epithelial barrier and provide clues as to how PTPN2 mutations may contribute to the pathophysiology of CD. PMID- 22671597 TI - Intracellular mediators of JAM-A-dependent epithelial barrier function. AB - Junctional adhesion molecule-A (JAM-A) is a critical signaling component of the apical junctional complex, a structure composed of several transmembrane and scaffold molecules that controls the passage of nutrients and solutes across epithelial surfaces. Observations from JAM-A-deficient epithelial cells and JAM-A knockout animals indicate that JAM-A is an important regulator of epithelial paracellular permeability; however, the mechanism(s) linking JAM-A to barrier function are not understood. This review highlights recent findings relevant to JAM-A-mediated regulation of epithelial permeability, focusing on the role of upstream and downstream signaling candidates. We draw on what is known about proteins reported to associate with JAM-A in other pathways and on known modulators of barrier function to propose candidate effectors that may mediate JAM-A regulation of epithelial paracellular permeability. Further investigation of pathways highlighted in this review may provide ideas for novel therapeutics that target debilitating conditions associated with barrier dysfunction, such as inflammatory bowel disease. PMID- 22671598 TI - Cingulin, paracingulin, and PLEKHA7: signaling and cytoskeletal adaptors at the apical junctional complex. AB - Cingulin, paracingulin, and PLEKHA7 are proteins localized in the cytoplasmic region of the apical junctional complex of vertebrate epithelial cells. Cingulin has been detected at tight junctions (TJs), whereas paracingulin has been detected at both TJs and adherens junctions (AJs) and PLEKHA7 has been detected at AJs. One function of cingulin and paracingulin is to regulate the activity of Rho family GTPases at junctions through their direct interaction with guanidine exchange factors of RhoA and Rac1. Cingulin also contributes to the regulation of transcription of several genes in different types of cultured cells, in part through its ability to modulate RhoA activity. PLEKHA7, together with paracingulin, is part of a protein complex that links E-cadherin to the microtubule cytoskeleton at AJs. In this paper, we review the current knowledge about these proteins, including their discovery, the characterization of their expression, localization, structure, molecular interactions, and their roles in different developmental and disease model systems. PMID- 22671599 TI - ZO-2, a tight junction scaffold protein involved in the regulation of cell proliferation and apoptosis. AB - ZO-2 is a membrane-associated guanylate kinase homologue (MAGUK) tight protein associated with the cytoplasmic surface of tight junctions. Here, we describe how ZO-2 is a multidomain molecule that binds to a variety of cell signaling proteins, to the actin cytoskeleton, and to gap, tight, and adherens junction proteins. In sparse cultures, ZO-2 is present at the nucleus and associates with molecules active in gene transcription and pre-mRNA processing. ZO-2 inhibits the Wnt signaling pathway, reduces cell proliferation, and promotes apoptosis; its absence, mutation, or overexpression is present in various human diseases, including deafness and cancer. PMID- 22671600 TI - From TER to trans- and paracellular resistance: lessons from impedance spectroscopy. AB - In epithelia and endothelia, overall resistance (TER) is determined by all ion conductive structures, such as membrane channels, tight junctions, and the intercellular space, whereas the epithelial capacitance is due to the hydrophobic phase of the plasma membrane. Impedance means alternating current resistance and, in contrast to ohmic resistance, takes into account that, e.g., capacitors become increasingly conductive with increasing frequency. Impedance spectroscopy uses the association of the capacitance with the transcellular pathway to distinguish between this capacitive pathway and purely conductive components (tight junctions, subepithelium). In detail, one-path impedance spectroscopy distinguishes the resistance of the epithelium from the resistance of subepithelial tissues. Beyond that, two-path impedance spectroscopy allows for the separation of paracellular resistance (governed by tight junctional properties) from transcellular resistance (determined by conductive structures residing in the cell membranes). The present paper reviews the basic principles of these techniques, some historic milestones, as well as recent developments in epithelial physiology. PMID- 22671601 TI - Diverse types of junctions containing tight junction proteins in stratified mammalian epithelia. AB - Molecular compositions and functions of tight junctions (TJs), that is, continuous, cell-cell-connecting zonulae occludentes serving as barrier structures for the paracellular transport of molecules and particles, have hitherto been determined for simple epithelia and for endothelia. In 2002, special TJ structures with barrier functions were identified in the stratum granulosum of mammalian epidermis. In addition, using biochemical and immunocytochemical methods, various types of TJ-type junctions have also been described that also contain claudins and/or occludin as well as typical TJ plaque proteins, in cell layers of all stratified squamous epithelia (e.g., various types of epidermis, gingiva, lingual, and other kinds of oral mucosa, pharynx, esophagus, trachea, vagina, and exocervix), including tissues without a lumen, such as the reticulum and Hassall corpuscles of the thymus, and tumors derived from such epithelia, notably squamous cell carcinomas. Biological and pathological aspects of TJ-related structures in such tissues are discussed. PMID- 22671602 TI - Barriers and more: functions of tight junction proteins in the skin. AB - Although the existence of tight junction (TJ) structures (or a secondary epidermal barrier) was postulated for a long time, the first description of TJ proteins in the epidermis (occludin, ZO-1, and ZO-2) was only fairly recent. Since then, a wealth of new insights concerning TJs and TJ proteins, including their functional role in the skin, have been gathered. Of special interest is that the epidermis as a multilayered epithelium exhibits a very complex localization pattern of TJ proteins, which results in different compositions of TJ protein complexes in different layers. In this review, we summarize our current knowledge about the role of TJ proteins in the epidermis in barrier function, cell polarity, vesicle trafficking, differentiation, and proliferation. We hypothesize that TJ proteins fulfill TJ structure-dependent and structure independent functions and that the specific function of a TJ protein may depend on the epidermal layer where it is expressed. PMID- 22671603 TI - Roles for claudins in alveolar epithelial barrier function. AB - Terminal airspaces of the lung, alveoli, are sites of gas exchange that are sensitive to disrupted fluid balance. The alveolar epithelium is a heterogeneous monolayer of cells interconnected by tight junctions at sites of cell-cell contact. Paracellular permeability depends on claudin (cldn)-family tight junction proteins. Of over a dozen alveolar cldns, cldn-3, cldn-4, and cldn-18 are the most highly expressed; other prominent alveolar claudins include cldn-5 and cldn-7. Cldn-3 is primarily expressed by type II alveolar epithelial cells, whereas cldn-4 and cldn-18 are expressed throughout the alveolar epithelium. Lung diseases associated with pulmonary edema, such as alcoholic lung syndrome and acute lung injury, affect alveolar claudin expression, which is frequently associated with impaired fluid clearance due to increased alveolar leak. However, recent studies have identified a role for increased cldn-4 in protecting alveolar barrier function following injury. Thus, alveolar claudins are dynamically regulated, tailoring lung barrier function to control the air-liquid interface. PMID- 22671605 TI - Relevance of endothelial junctions in leukocyte extravasation and vascular permeability. AB - Inflammation and immune surveillance rely on the ability of leukocytes to leave the blood stream and enter tissue. Cytokines and chemokines regulate expression and the activation state of adhesion molecules that enable leukocytes to adhere and arrest at sites of leukocyte exit. Capturing and arrest is followed by the transmigration of leukocytes through the vessel wall-a process called diapedesis. The review will focus on recently published novel approaches to determine the route that leukocytes take in vivo when they migrate through the endothelial layer of blood vessels. This work has revealed the dominant importance of the junctional pathway between endothelial cells in vivo. In addition, recent progress has improved our understanding of the molecular mechanisms that regulate junctional stability, the opening of endothelial junctions during leukocyte extravasation, and the induction of vascular permeability. PMID- 22671604 TI - Claudins and alveolar epithelial barrier function in the lung. AB - The alveolar epithelium of the lung constitutes a unique interface with the outside environment. This thin barrier must maintain a surface for gas transfer while being continuously exposed to potentially hazardous environmental stimuli. Small differences in alveolar epithelial barrier properties could therefore have a large impact on disease susceptibility or outcome. Moreover, recent work has focused attention on the alveolar epithelium as central to several lung diseases, including acute lung injury and idiopathic pulmonary fibrosis. Although relatively little is known about the function and regulation of claudin tight junction proteins in the lung, new evidence suggests that environmental stimuli can influence claudin expression and alveolar barrier function in human disease. This review considers recent advances in the understanding of the role of claudins in the breakdown of the alveolar epithelial barrier in disease and in epithelial repair. PMID- 22671606 TI - Involvement of claudins in zebrafish brain ventricle morphogenesis. AB - Zebrafish brain ventricle morphogenesis involves an initial circulation independent opening followed by a blood flow- and circulation-dependent expansion process. Zebrafish claudin-5a is required for the establishment of a neuroepithelial-ventricular barrier, which maintains the hydrostatic pressure within the ventricular cavity, thereby contributing to brain ventricle opening and expansion. In mammalia, several claudin family members, including claudin-3 and claudin-5, are expressed within microvessel endothelial cells of the blood brain barrier. Whether zebrafish brain ventricle morphogenesis provides a model for studying these claudins during early embryonic development was unknown. This review focuses on the expression and function of these zebrafish claudins during brain ventricle morphogenesis. PMID- 22671607 TI - Modulation of tight junction proteins in the perineurium for regional pain control. AB - Peripheral neurons are surrounded by the perineurium that forms the blood-nerve barrier and protects the nerve. Although the barrier serves as protection, it also hampers drug delivery of analgesic drugs to the peripheral nerve. We previously showed that opening of the barrier using hypertonic solutions facilitates drug delivery, for example, of hydrophilic opioids, which selectively target nociceptors. The perineurial barrier is formed by tight junction proteins, including claudin-1, claudin-5, and occludin. Under pathophysiological conditions such as nerve crush injury, the perineurial barrier is opened and tight junction proteins are no longer present. After several days, tight junction proteins reappear and the barrier reseals. Similarly, perineurial injection of hypertonic saline transiently opens the barrier, claudin-1 disappears, and hydrophilic analgesic drugs are effective. In the future, these findings could be used to reseal the barrier breakdown and could be applied to other barriers like the blood-brain or the intestinal mucosal barrier. PMID- 22671689 TI - Identification and quantification of base flow using carbon isotopes. AB - Six surface water samples from locations along Otter Creek in Southeastern Montana and a groundwater sample from a nearby monitoring well completed in the Knobloch coal were analyzed for stable carbon isotope ratios. Along the length of its perennial reach, between the towns of Otter and Ashland, Otter Creek crosses several coal outcrops, including the Knobloch coal zone. The carbon isotope ratio of the creek becomes progressively more similar to that of the Knobloch coal aquifer groundwater in samples collected downgradient from the town of Otter. The isotope ratio of the stream changes from -10.5 to -8.90/00 reflecting the influence of the coal-aquifer base flow contribution, as represented by Knobloch coal groundwater, which has a carbon isotope value of +3.90/00. The dissolved inorganic carbon concentrations of the groundwater and surface water are similar (~100 mg/L), which allowed the use of the simplified, first-order, two-end-member mixing equation. Using carbon isotope ratios, calculations of the fraction of water contributed by coal aquifers indicate that approximately 11% of the surface water in Otter Creek at its mouth near Ashland was supplied by groundwater from the coal aquifers that crop out between Otter and Ashland. This study was conducted in December, when Otter Creek is at low flow. At times of higher surface flow, the contribution from groundwater base flow will be correspondingly smaller. This study illustrates that carbon isotopes can be an effective, low cost tool in base flow studies. PMID- 22671691 TI - Molecular clock evidence for survival of Antarctic cyanobacteria (Oscillatoriales, Phormidium autumnale) from Paleozoic times. AB - Cyanobacteria are well adapted to freezing and desiccation; they have been proposed as possible survivors of comprehensive Antarctic glaciations. Filamentous types from the order Oscillatoriales, especially the species Phormidium autumnale Kutzing ex Gomont 1892, have widely diverse morphotypes that dominate in Antarctic aquatic microbial mats, seepages, and wet soils. Currently little is known about the dispersion of cyanobacteria in Antarctica and of their population history. We tested the hypothesis that cyanobacteria survived Antarctic glaciations directly on site after the Gondwana breakup by using the relaxed and strict molecular clock in the analysis of the 16S rRNA gene. We estimated that the biogeographic history of Antarctic cyanobacteria belonging to P. autumnale lineages has ancient origins. The oldest go further back in time than the breakup of Gondwana and originated somewhere on the supercontinent between 442 and 297 Ma. Enhanced speciation rate was found around the time of the opening of the Drake Passage (c. 31-45 Ma) with beginning of glaciations (c. 43 Ma). Our results, based primarily on the strains collected in maritime Antarctica, mostly around James Ross Island, support the hypothesis that long term survival took place in glacial refuges. The high morphological diversification of P. autumnale suggested the coevolution of lineages and formation of complex associations with different morphologies, resulting in a specific endemic Antarctic cyanobacterial flora. PMID- 22671690 TI - Recent advances in the discovery and preclinical testing of novel compounds for the prevention and/or treatment of alcohol use disorders. AB - Alcohol abuse and dependence have a staggering socioeconomic impact, yet current therapeutic strategies are largely inadequate to treat these disorders. Thus, the development of new strategies that can effectively prevent alcohol use disorders (AUDs) is of paramount importance. Currently approved medications attempt to deter alcohol intake by blocking ethanol metabolism or by targeting the neurochemical systems downstream of the cascades leading to craving and dependence. Unfortunately, these medications have provided only limited success as indicated by the continued high rates of alcohol abuse and alcoholism. The lack of currently available effective treatment strategies is highlighted by the urgent call by the NIAAA to find new and paradigm-changing therapeutics to either prevent or treat alcohol-related problems. This mini-review highlights recent findings from 4 laboratories with a focus on compounds that have the potential to be novel therapeutic agents that can be developed for the prevention and/or treatment of AUDs. PMID- 22671692 TI - Isolation and characterization of Cronobacter from desiccated foods in Korea. AB - A total of 115 desiccated food samples, including agricultural and marine products, were investigated for the presence of Cronobacter. Cronobacter species were characterized with biochemical tests. Antibiotic resistance was assessed with the disk diffusion method, and the molecular subtypes of Cronobacter isolates were identified using an automated repetitive sequence-based PCR (rep PCR) system. A total of 18 (15.7%) Cronobacter strains were isolated from 115 desiccated food products. Fifteen Cronobacter isolates were C. sakazakii (13%), followed by 2 C. dublinensis (1.7%), and 1 C. universalis (0.9%). The most common antibiotic resistance of Cronobacter observed was against cephalothin (77.8%) followed by ampicillin (5.6%). With exception of 2 strains, all Cronobacter strains isolated from different sources were successfully differentiated by using the automated rep-PCR system, indicating that it can be used for the purpose of contamination or outbreak source tracking of the bacteria. PMID- 22671693 TI - Producing pronouns and definite noun phrases: do speakers use the addressee's discourse model? AB - We report two experiments that investigated the widely held assumption that speakers use the addressee's discourse model when choosing referring expressions (e.g., Ariel, 1990; Chafe, 1994; Givon, 1983; Prince, 1985), by manipulating whether the addressee could hear the immediately preceding linguistic context. Experiment 1 showed that speakers increased pronoun use (and decreased noun phrase use) when the referent was mentioned in the immediately preceding sentence compared to when it was not, even though the addressee did not hear the preceding sentence, indicating that speakers used their own, privileged discourse model when choosing referring expressions. The same pattern of results was found in Experiment 2. Speakers produced more pronouns when the immediately preceding sentence mentioned the referent than when it mentioned a referential competitor, regardless of whether the sentence was shared with their addressee. Thus, we conclude that choice of referring expression is determined by the referent's accessibility in the speaker's own discourse model rather than the addressee's. PMID- 22671694 TI - Identification of a novel HLA-DQB1*03:38 allele by polymerase chain reaction sequence-based typing in a Chinese bone marrow donor. AB - HLA-DQB1*03:38 differs from HLA-DQB1*03:03:02:01 at nucleotide position 184 T>C in exon 2. PMID- 22671695 TI - Synthesis of chiral helical 1,3-oxazines. AB - A series of novel 1,3-oxazines were prepared to construct a helical framework. The 1,3-oxazine attached to the phenanthrene unit showed a small bite angle theta (~12 degrees ), while the units attached to [4]helicene showed a larger theta (~35 degrees ) and exhibited helical isomers at ambient conditions. The diastereomers of the third type of helicene-like bis-oxazine attached to binaphthyl were easily separable and showed good thermal stability. All four diastereomers of bis-helicene were synthesized, and their absolute configuration was established. PMID- 22671696 TI - A chemical small molecule induces mouse embryonic stem cell differentiation into functional vascular endothelial cells via Hmbox1. AB - Embryonic stem cells (ESCs) can differentiate to endothelial progenitor cells and vascular endothelial cells (VECs), but the mechanism is largely unknown. In this study, we synthesized 2 chiral compounds (R-ABO and S-ABO) and identified R-ABO as an effective inducer of ESC differentiation into VECs. Furthermore, we found that R-ABO induced ESC differentiation into VECs via homeobox containing 1 (Hmbox1) that acted upstream of fibroblast growth factor 2 (FGF-2). The data suggest that R-ABO is a novel tool for ESC differentiation into VECs, and Hmbox1 is a key regulator in this differentiation process. These findings provide information on a novel target and a new platform for further investigating the gene control of ESC differentiation to VECs. PMID- 22671697 TI - The spectrum of spitzoid tumours: A clinical study. AB - This study explores the relationship between different types of spitzoid tumours, spindle cell naevus of Reed and spitzoid melanomas. Clinical and histopathological data were retrospectively reviewed from our hospital database in Cambridge from January 2006 to July 2009. Clinical images, where available, were recorded. Search headings from our pathology database included 'spitzoid tumours', 'Spitz naevi', 'atypical spitzoid tumours', spitzoid tumours of uncertain malignant potential ('STUMP'), 'spindle cell naevus of Reed' and 'spitzoid melanomas'. The total number of spitzoid tumours was 118 comprising Spitz naevi (72), atypical spitzoid tumours (30), spitzoid melanomas (eight), and other naevi with spitzoid features (eight). In total, 60% of Spitz naevi were diagnosed clinically and 50% reported a history of change with spitzoid melanoma, compared with 32% with Spitz naevi. In all, 60% of Spitz naevi and atypical spitzoid tumours were pigmented in contrast with spitzoid melanomas (83%). Variegated pigmentation was found in 20% of Spitz naevi and atypical spitzoid tumours, however, no spitzoid melanomas had mixed pigmentation. There were 30 atypical spitzoid tumours (9 M : 21 F); 16 occurred on the lower limbs, peaking in the 20-30-years age group. There were eight patients with spitzoid melanomas with a 7:1 F : M ratio, 50% of which were diagnosed clinically. Of the 34 spindle cell naevus of Reed (10 M : 24 F), 31 were misdiagnosed, most commonly as melanoma. Reed naevi peaked in the 30-40 year age group and on the upper limbs and lower limbs in the 20-30-years age group. In summary, age and sex appeared helpful in distinguishing benign from malignant spitzoid tumours, however history was less discriminatory. Spitzoid melanomas, most of which were pigmented occurred more commonly in females. Atypical spitzoid tumours were more common in females and pathologists favoured malignancy in this group beyond 20 years of age. PMID- 22671698 TI - How and when do students use flashcards? AB - Previous survey research has documented students' use of self-regulated study strategies, with a particular interest in self-testing. These surveys indicate that students frequently use flashcards to self-test and that self-testing is primarily used as a way to monitor learning. Whereas previous surveys provide information about whether and why students self-test, they provide minimal information about how and when students choose to self-test. Accordingly, the primary purpose of the current survey was to explore how and when students engage in self-testing. We surveyed 374 undergraduates about the amount of practice and the timing of practice, two factors that strongly affect the efficacy of self testing. Results indicate that students understand the benefits of practising to higher criterion levels (amount of practice) but do not typically implement or understand the benefits of practising with longer lags (timing of practice). We discuss practical implications for supporting more successful student learning. PMID- 22671699 TI - Predicting levels of basic functional mobility, as assessed by the Timed "Up and Go" test, for individuals with stroke: discriminant analyses. AB - PURPOSE: To compare stroke subjects with different levels of functional mobility, as determined by the Timed "Up and Go" (TUG) test, with controls and outline which clinical functional measures could be combined to predict functional mobility. METHOD: Twenty-two chronic stroke (54.7 +/- 15.4 years) and 22 healthy subjects (54.7 +/- 15.4 years) performed the TUG and were assessed regarding the paretic or non-dominant quadriceps strength, maximal gait speed, and quality of life (QL). Each group was divided into fast, intermediate, and slow sub-groups regarding their TUG performances. ANOVAs were employed to investigate the main and interaction effects between the groups and sub-groups and discriminant analyses to predict group membership. RESULTS: For both groups, the three sub groups were significantly different regarding their TUG scores (26.21 < F < 32.73; p < 0.006). The significant interactions indicated that faster stroke subjects demonstrated similar TUG scores, compared to those of all the healthy sub-groups. Maximal gait speed and QL showed significant discriminant functions and correctly classified 86.4% of the original grouped cases. CONCLUSIONS: Fast stroke subjects demonstrated similar TUG performances compared to those of healthy subjects. Group membership was correctly classified for the majority of subjects, except for the fast stroke sub-group, but only for the variables related to gait speed and QL. PMID- 22671700 TI - Cue effectiveness in communicatively efficient discourse production. AB - Recent years have seen a surge in accounts motivated by information theory that consider language production to be partially driven by a preference for communicative efficiency. Evidence from discourse production (i.e., production beyond the sentence level) has been argued to suggest that speakers distribute information across discourse so as to hold the conditional per-word entropy associated with each word constant, which would facilitate efficient information transfer (Genzel & Charniak, 2002). This hypothesis implies that the conditional (contextualized) probabilities of linguistic units affect speakers' preferences during production. Here, we extend this work in two ways. First, we explore how preceding cues are integrated into contextualized probabilities, a question which so far has received little to no attention. Specifically, we investigate how a cue's maximal informativity about upcoming words (the cue's effectiveness) decays as a function of the cue's recency. Based on properties of linguistic discourses as well as properties of human memory, we analytically derive a model of cue effectiveness decay and evaluate it against cross-linguistic data from 12 languages. Second, we relate the information theoretic accounts of discourse production to well-established mechanistic (activation-based) accounts: We relate contextualized probability distributions over words to their relative activation in a lexical network given preceding discourse. PMID- 22671701 TI - Case of Conradi-Hunermann-Happle syndrome with alopecia: Histological examination of affected follicles. PMID- 22671702 TI - GeLC-MRM quantitation of mutant KRAS oncoprotein in complex biological samples. AB - Tumor-derived mutant KRAS (v-Ki-ras-2 Kirsten rat sarcoma viral oncogene) oncoprotein is a critical driver of cancer phenotypes and a potential biomarker for many epithelial cancers. Targeted mass spectrometry analysis by multiple reaction monitoring (MRM) enables selective detection and quantitation of wild type and mutant KRAS proteins in complex biological samples. A recently described immunoprecipitation approach (Proc. Nat. Acad. Sci.2011, 108, 2444-2449) can be used to enrich KRAS for MRM analysis, but requires large protein inputs (2-4 mg). Here, we describe sodium dodecyl sulfate-polyacrylamide gel electrophoresis-based enrichment of KRAS in a low molecular weight (20-25 kDa) protein fraction prior to MRM analysis (GeLC-MRM). This approach reduces background proteome complexity, thus, allowing mutant KRAS to be reliably quantified in low protein inputs (5-50 MUg). GeLC-MRM detected KRAS mutant variants (G12D, G13D, G12V, G12S) in a panel of cancer cell lines. GeLC-MRM analysis of wild-type and mutant was linear with respect to protein input and showed low variability across process replicates (CV = 14%). Concomitant analysis of a peptide from the highly similar HRAS and NRAS proteins enabled correction of KRAS-targeted measurements for contributions from these other proteins. KRAS peptides were also quantified in fluid from benign pancreatic cysts and pancreatic cancers at concentrations from 0.08 to 1.1 fmol/MUg protein. GeLC-MRM provides a robust, sensitive approach to quantitation of mutant proteins in complex biological samples. PMID- 22671703 TI - Normalized CCND1 expression has prognostic value in mantle cell lymphoma. PMID- 22671704 TI - The method of en face frozen section in clearing periocular basal cell carcinoma and squamous cell carcinoma. AB - BACKGROUND: The senior consultants Ross Benger and Andrew Gal have been using en face frozen section histological margin control in removing cancer from the periocular region since 1985. The aim of this study was to determine the percentage of cases in which more than one resection was necessary in order to achieve clear margins. METHODS: This is a retrospective study of patients treated at Drummoyne Eye Surgical Centre in the period 1999-2007, in whom removal of the eyelid cancer was decided to be with en face frozen section histological control. A record was kept of how many resections were necessary to achieve clear margins. Paraffin sections were subsequently examined for a final histopathological diagnosis. RESULTS: Two hundred and fifty people were included in the study, of whom 204 had basal cell carcinoma (BCC) and 32 had squamous cell carcinoma (SCC). One hundred and twenty BCCs had a full-thickness eyelid "wedge" resection, of which 45% needed more than the standard two frozen sections taken to achieve clear margins. Eighty-four BCCs were removed using ring resection, of which 35.7% needed more than the standard initial resections (peripheral annulus and deep disc) to achieve clear margins. CONCLUSIONS: Our study showed that a significant percentage of BCC and SCC lesions needed further resection after the initial frozen section edge checks to achieve clear margins. Intraoperative presence of the histopathologist increased the likelihood of achieving clearance of the cancer at a single operating session. PMID- 22671705 TI - A novel cross-talk between endothelin and ErbB receptors controlling glutamate transporter expression in astrocytes. AB - The endothelin and epidermal growth factor (EGF) systems are central to the control of reactive brain processes and are thought to partly exert these tasks by endothelin-induced transactivation of the epidermal growth factor receptor (EGFR) Here we show that beyond EGFR transactivation, endothelins prevent the ligand-induced internalization of the EGFR. We unravel that endothelins abrogate internalization of the EGFR by either promoting the formation of "internalization deficient" EGFR/ErB2-heterodimers or by activating c-Abl kinase, a negative regulator of EGFR internalization. We further provide evidence that this cross talk is operational in the control of astrocytic glutamate transport. Specifically, we establish that the inhibitory effects exerted by endothelins on basal as well as EGF-induced expression of the major astroglial glutamate transporter subtype, glutamate transporter 1, are a direct consequence of the endothelin-dependent retention of the EGFR at the cell surface. Together our findings unravel a previously unknown cross-talk between endothelin and epidermal growth factor receptors, which may have implications for a variety of pathological conditions. PMID- 22671706 TI - Atopic dermatitis: a candidate for disease-modifying strategy. AB - The concept of disease modification has been introduced to define the therapeutic strategies aimed to break, stop, or reverse the natural course of a chronic invalidating disease. This strategy is tightly related to the biomarker-based stratification of affected patients using genetic and other biological markers. With regard to the progress in understanding the genetic background of atopic dermatitis (AD), its natural history and its pivotal role in the emergence of allergic asthma, the time is mature to foster the research field of biomarkers in AD and to consider the elaboration of disease-modifying strategies in the management of AD with the goal to stop or even reverse the atopic march. PMID- 22671707 TI - Sequence-based HLA high-resolution typing of a bone marrow donor/recipient pair reveals the novel HLA allele HLA-C*07:208. AB - Nucleotide sequence of HLA-C*07:208 allele was different from that of HLA C*07:02:01:01 by a single-nucleotide substitution at position 475 G>C. PMID- 22671708 TI - Fluorescence switching of imidazo[1,5-a]pyridinium ions: pH-sensors with dual emission pathways. AB - Imidazo[1,5-a]pyridinium ions are identified as highly emissive and water-soluble fluorophores accessed by an efficient three-component coupling reaction. Synthetic modifications of groups conjugated to the polyheterocyclic core are shown to profoundly impact the emission properties of these molecules. Notably, two structural isomers of functionalized imidazo[1,5-a]pyridinium ions were found to exhibit distinct de-excitation pathways, which are responsible for either a fluorescence turn-on or ratiometric response to pH change. PMID- 22671709 TI - The active fixation coronary sinus lead: more peril than promise? PMID- 22671710 TI - Lessons from ICD lead recalls: what have we learned? PMID- 22671711 TI - Small molecule inhibitors promote efficient generation of induced pluripotent stem cells from human skeletal myoblasts. AB - Human somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) by ectopic expression of key transcription factors. iPSCs have been generated from a variety of cell types. However, iPSC induction from human myoblasts has not yet been reported. Human primary skeletal myoblasts can be cultured from diagnostic muscle biopsy specimens, and thousands of lines are frozen and stored in biobanks, and are a valuable source for iPSC-based etiological and pathogenic studies. Our aim was to generate iPSCs from human skeletal myoblasts enriched from muscle biopsy samples. We used retro- or Sendai virus vector-mediated reprogramming of enriched human myoblasts from 7 donors. We show that stable iPSC lines can be generated from human myoblasts at efficiency similar to that of fibroblasts when appropriate media is used, and the efficiency of the feeder-free iPSC generation can be significantly improved by inhibitors of histone deacetylase (sodium butyrate) and TGF-beta signaling (SB431542). PMID- 22671712 TI - Meaning of work and the returning process after breast cancer: a longitudinal study of 56 women. AB - BACKGROUND: An increasing number of women survive breast cancer and a majority return to work. However, findings based on mean values may conceal individual processes that need to be better understood to discuss meaningful rehabilitation. AIM: The purpose of this study is to describe the sick-leave pattern of a group of Swedish women with primary breast cancer but foremost to explore their ideas about what motivates and discourages their return to work. METHOD: Fifty-six women were repeatedly interviewed over a period of 18-24 months. Interview sections that clearly illustrated the women's experiences and ideas about work were categorized using the comparative similarities-differences technique. FINDINGS: The average length of sick leave was 410 days (range 0-942). Six months after the first day of sick leave, 29% worked at least their previous service grade. At 12 months, 55% and at 18 months 57% did so. Those treated with chemotherapy had in average more than twice as large sick leave as those who did not. Three categories emerged. 'Motives for not returning to work' consists of four subcategories: 'I'm still too fragile to return to work'; 'My workplace is a discouraging place'; 'I took an opportunity to pause' and 'I've lost the taste for work'. 'Motives for returning' consists of two sub-categories: 'Work generates and structures my everyday life' and 'I miss my workplace'. Finally, 'Transition in work approach' reflects a changed approach to work. CONCLUSION: The meaning of work varies over time, but first and foremost work was regarded as an important part of the healing process as it restores the disruption of everyday life. Guidelines cannot be reduced to a linear relationship with biomedical variables but the individual context of everyday life must be considered. PMID- 22671714 TI - The 2012 AHS/AAN guidelines for prevention of episodic migraine: a summary and comparison with other recent clinical practice guidelines. AB - BACKGROUND: Updated guidelines for the preventive treatment of episodic migraine have been issued by the American Headache Society (AHS) and the American Academy of Neurology (AAN). We summarize key 2012 guideline recommendations and changes from previous guidelines. We review the characteristics, methods, consistency, and quality of the AHS/AAN guidelines in comparison with recently issued guidelines from other specialty societies. METHODS: To accomplish this, we reviewed the AHS/AAN guidelines and identified comparable recent guidelines through a systematic MEDLINE search. We extracted key data, and summarized and compared the key recommendations and assessed quality using the Appraisal of Guidelines Research and Evaluation-II (AGREE-II) tool. We identified 2 additional recent guidelines for migraine prevention from the Canadian Headache Society and the European Federation of Neurological Societies. All of the guidelines used structured methods to locate evidence and linked recommendations with assessment of the evidence, but they varied in the methods used to derive recommendations from that evidence. RESULTS: Overall, the 3 guidelines were consistent in their recommendations of treatments for first-line use. All rated topiramate, divalproex/sodium valproate, propranolol, and metoprolol as having the highest level of evidence. In contrast, recommendations diverged substantially for gabapentin and feverfew. The overall quality of the guidelines ranged from 2 to 6 out of 7 on the AGREE-II tool. CONCLUSION: The AHS/AAN and Canadian guidelines are recommended for use on the basis of the AGREE-II quality assessment. Recommendations for the future development of clinical practice guidelines in migraine are provided. In particular, efforts should be made to ensure that guidelines are regularly updated and that guideline developers strive to locate and incorporate unpublished clinical trial evidence. PMID- 22671715 TI - Migraine relieved by chilis. PMID- 22671716 TI - Motor deficits associated with mild, chronic hyponatremia: a factor analytic study. AB - Chronic hyponatremia (CHN) has traditionally been considered asymptomatic. If symptoms are observed, they are often mistakenly attributed to the underlying disorder. However, in recent studies neuropsychological deficits have been associated with CHN. The authors sought to determine the association between CHN and motor deficits. They used previously collected data, and 41 subjects with hyponatremia were included. An exploratory factor analysis with principal component analysis (PCA) was performed (eigenvalues >1.0). Factor scores were generated for each subject based on the resultant PCA factor structure. Finally, partial correlations were computed to measure the degree of association between baseline serum sodium concentration [Na+] and individual neuropsychological factor scores with the effect of age removed. All significance tests were performed using 2-tailed comparisons with alpha level of p <= .05. A 3-factor model emerged accounting for 70.17% of the total variance, including 1 factor that loaded primarily with motor speed and reaction time. A significant correlation was observed between this motor factor and serum [Na+] (r = -.477, p = .002). These findings add to previous observations suggesting that CHN is associated with subtle yet harmful motor deficits. PMID- 22671717 TI - Validity and reliability of the Chinese translation of the Physical Activity Scale for the Elderly (PASE). AB - PURPOSE: To translate and assess the reliability and validity of a Chinese version of the Physical Activity Scale for the Elderly (PASE). METHODS: Participants included Chinese individuals >65 living in the community or assistive living facilities. At baseline, 73 subjects completed the translated PASE, and Chinese versions of three other scales to evaluate validity; the Timed Up and Go (TUG), the Older American Resources Services Activities of Daily Living (OARS ADL), and the Activities Balance Confidence Scale (ABC). At follow-up, 66 subjects completed the PASE and a questionnaire to determine if there were any changes in health over the retest period. RESULTS: The mean baseline PASE-C score was 76.0 (+/-49.1) at baseline and 78.33 (+/-50.27) at follow up. Correlations between the PASE-C and other variables were: age r = -0.51; TUG r = -0.52; OARS ADL r = 0.56 and ABC score r = 0.62. The retest reliability was ICC = 0.79 (95% confidence interval 0.68-0.86). CONCLUSION: Our results indicate that the PASE-C has acceptable reliability and there is support for validity in the older Chinese population. PMID- 22671718 TI - Inactivation of Listeria monocytogenes on ham and bologna using pectin-based apple, carrot, and hibiscus edible films containing carvacrol and cinnamaldehyde. AB - Edible films can be used as wrapping material on food products to reduce surface contamination. The incorporation of antimicrobials into edible films could serve as an additional barrier against pathogenic and spoilage microorganisms that contaminate food surfaces. The objective of this study was to investigate the antimicrobial effects of carvacrol and cinnamaldehyde, incorporated into apple, carrot, and hibiscus-based edible films against Listeria monocytogenes on contaminated ham and bologna. Ham or bologna samples were inoculated with L. monocytogenes and dried for 30 min, then surface wrapped with edible films containing the antimicrobials at various concentrations. The inoculated, film wrapped samples were stored at 4 degrees C. Samples were taken at day 0, 3, and 7 for enumeration of surviving L. monocytogenes by plating on appropriate media. Carvacrol films showed better antimicrobial activity than cinnamaldehyde films. Compared to control films without antimicrobials, films with 3% carvacrol induced 1 to 3, 2 to 3, and 2 to 3 log CFU/g reductions on ham and bologna at day 0, 3, and 7, respectively. Corresponding reductions with 1.5% carvacrol were 0.5 to 1, 1 to 1.5, and 1 to 2 logs, respectively. At day 7, films with 3% cinnamaldehyde reduced L. monocytogenes population by 0.5 to 1.5 and 0.5 to 1.0 logs on ham and bologna, respectively. Inactivation by apple films was greater than that by carrot or hibiscus films. Apple films containing 3% carvacrol reduced L. monocytogenes population on ham by 3 logs CFU/g on day 0 which was 1 to 2 logs greater than that by carrot and hibiscus films. Films were more effective on ham than on bologna. The food industry and consumers could use these films to control surface contamination by pathogenic microorganisms. PRACTICAL APPLICATION: Antimicrobial edible, food-compatible film wraps prepared from apples, carrots, and hibiscus calyces can be used by the food industry to inactivate Listeria monocytogenes on widely consumed ready to eat meat products such as bologna and ham. This study provides a scientific basis for large-scale application of edible fruit- and vegetable-based antimicrobial films on foods to improve microbial food safety. PMID- 22671719 TI - The effect of nanoparticle polyethylene glycol surface density on ligand-directed tumor targeting studied in vivo by dual modality imaging. AB - The development and application of nanoparticles as in vivo delivery vehicles for therapeutic and/or diagnostic agents has seen a drastic growth over the last decades. Novel imaging techniques allow real-time in vivo study of nanoparticle accumulation kinetics at the level of the cell and targeted tissue. Successful intravenous application of such nanocarriers requires a hydrophilic particle surface coating, of which polyethylene glycol (PEG) has become the most widely studied and applied. In the current study, the effect of nanoparticle PEG surface density on the targeting efficiency of ligand-functionalized nanoemulsions was investigated. We synthesized 100 nm nanoemulsions with a PEG surface density varying from 5 to 50 mol %. Fluorescent and paramagnetic lipids were included to allow their multimodal detection, while RGD peptides were conjugated to the PEG coating to obtain specificity for the alpha(v)beta(3)-integrin. The development of a unique experimental imaging setup allowed us to study, in real time, nanoparticle accumulation kinetics at (sub)-cellular resolution in tumors that were grown in a window chamber model with confocal microscopy imaging, and at the macroscopic tumor level in subcutaneously grown xenografts with magnetic resonance imaging. Accumulation in the tumor occurred more rapidly for the targeted nanoemulsions than for the nontargeted versions, and the PEG surface density had a strong effect on nanoparticle targeting efficiency. Counterintuitively, yet consistent with the PEG density conformation models, the highest specificity and targeting efficiency was observed at a low PEG surface density. PMID- 22671722 TI - How young children learn from examples: descriptive and inferential problems. AB - Three experiments with preschool- and young school-aged children (N = 75 and 53) explored the kinds of relations children detect in samples of instances (descriptive problem) and how they generalize those relations to new instances (inferential problem). Each experiment initially presented a perfect biconditional relation between two features (e.g., all and only frogs are blue). Additional examples undermined one of the component conditional relations (not all frogs are blue) but supported another (only frogs are blue). Preschool-aged children did not distinguish between supported and undermined relations. Older children did show the distinction, at least when the test instances were clearly drawn from the same population as the training instances. Results suggest that younger children's difficulties may stem from the demands of using imperfect correlations for predictions. Older children seemed sensitive to the inferential problem of using samples to make predictions about populations. PMID- 22671761 TI - Circumscribed alopecia areata incognita. AB - The characteristic lesion of alopecia areata is a smooth bald patch on the scalp. When there is no bald surface it is called alopecia areata incognita. To date, all cases of alopecia areata reported as so-called 'incognito' have shown a diffuse involvement of the scalp as in acute telogen effluvium. Recently, we have observed two patients who showed localised hair thinning of the scalp without bald spots. Histopathologically, the lesions were typical of alopecia areata with peribulbar lymphocytic infiltrates. The response to corticosteroid treatment and its clinical course were also compatible with alopecia areata. PMID- 22671763 TI - Tissue proteomics by one-dimensional gel electrophoresis combined with label-free protein quantification. AB - Label-free methods streamline quantitative proteomics of tissues by alleviating the need for metabolic labeling of proteins with stable isotopes. Here we detail and implement solutions to common problems in label-free data processing geared toward tissue proteomics by one-dimensional gel electrophoresis followed by liquid chromatography tandem mass spectrometry (geLC MS/MS). Our quantification pipeline showed high levels of performance in terms of duplicate reproducibility, linear dynamic range, and number of proteins identified and quantified. When applied to the liver of an adenomatous polyposis coli (APC) knockout mouse, we demonstrated an 8-fold increase in the number of statistically significant changing proteins compared to alternative approaches, including many more previously unidentified hydrophobic proteins. Better proteome coverage and quantification accuracy revealed molecular details of the perturbed energy metabolism. PMID- 22671762 TI - Caffeine provokes adverse interactions with 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') and related psychostimulants: mechanisms and mediators. AB - Concomitant consumption of caffeine with recreational psychostimulant drugs of abuse can provoke severe acute adverse reactions in addition to longer term consequences. The mechanisms by which caffeine increases the toxicity of psychostimulants include changes in body temperature regulation, cardiotoxicity and lowering of the seizure threshold. Caffeine also influences the stimulatory, discriminative and reinforcing effects of psychostimulant drugs. In this review, we consider our current understanding of such caffeine-related drug interactions, placing a particular emphasis on an adverse interaction between caffeine and the substituted amphetamine, 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy'), which has been most recently described and characterized. Co-administration of caffeine profoundly enhances the acute toxicity of MDMA in rats, as manifested by high core body temperature, tachycardia and increased mortality. In addition, co administration of caffeine enhances the long-term serotonergic neurotoxicity induced by MDMA. Observations to date support an interactive model of drug induced toxicity comprising MDMA-related enhancement of dopamine release coupled to a caffeine-mediated antagonism of adenosine receptors in addition to inhibition of PDE. These experiments are reviewed together with reports of caffeine-related drug interactions with cocaine, d-amphetamine and ephedrine where similar mechanisms are implicated. Understanding the underlying mechanisms will guide appropriate intervention strategies for the management of severe reactions and potential for increased drug-related toxicity, resulting from concomitant caffeine consumption. PMID- 22671764 TI - T cells producing the anti-inflammatory cytokine IL-10 regulate allergen-specific Th2 responses in human airways. AB - BACKGROUND: Murine models suggest a critical functional role for the anti inflammatory cytokine IL-10 in local regulation of allergic airways inflammation. There is little corresponding information on human airway cells. This study aimed to investigate whether local IL-10 production regulates responses by respiratory mucosal leucocytes isolated from nasal polyps. MATERIALS AND METHODS: Nasal polyp tissue was harvested from 24 patients sensitised to aeroallergens with chronic rhinitis and polyposis undergoing routine polypectomy. Cells were isolated by matrix proteolysis. Cytokine production by polyp cells was determined by cytometric bead array (CBA) and intracellular cytokine analysis. Surface marker expression by polyp cells was determined by flow cytometry. RESULTS: Allergen stimulation significantly enhanced production of IL-10, but not IL-5 or IFN-gamma by nasal polyp cell suspensions. Under the same conditions, neutralisation of IL 10 significantly increased allergen-specific IL-5 and IFN-gamma production by nasal polyp cells. Cell depletion experiments showed that T cells themselves were primarily responsible for IL-10 production or for inducing its production by other cells. Intracellular cytokine staining confirmed production of IL-10 in the absence of IL-2 production by T cells in response to allergen. CONCLUSION: T cells within the human respiratory mucosa produce IL-10, which is capable of inhibiting pro-inflammatory Th2 and Th1 cytokine production in an antigen specific fashion. PMID- 22671765 TI - Giant cell arteritis and polymyalgia rheumatica after influenza vaccination: comparing different experiences. PMID- 22671766 TI - Toward intracellular targeted delivery of cancer therapeutics: progress and clinical outlook for brain tumor therapy. AB - A number of anti-cancer drugs have their targets localized to particular intracellular compartments. These drugs reach the targets mainly through diffusion, dependent on biophysical and biochemical forces that allow cell penetration. This means that both cancer cells and normal cells will be subjected to such diffusion; hence many of these drugs, like chemotherapeutics, are potentially toxic and the concentration achieved at the site of their action is often suboptimal. The same relates to radiation that indiscriminately affects normal and diseased cells. However, nature-designed systems enable compounds present in the extracellular environment to end up inside the cell and even travel to more specific intracellular compartments. For example, viruses and bacterial toxins can more or less specifically recognize eukaryotic cells, enter these cells, and direct some protein portions to designated intracellular areas. These phenomena have led to creative thinking, such as employing viruses or bacterial toxins for cargo delivery to cells and, more specifically, to cancer cells. Proteins can be genetically engineered in order to not only mimic what viruses and bacterial toxins can do, but also to add new functions, extending or changing the intracellular routes. It is possible to make conjugates or, more preferably, single-chain proteins that recognize cancer cells and deliver cargo inside the cells, even to the desired subcellular compartment. These findings offer new opportunities to deliver drugs/labels only to cancer cells and only to their site of action within the cells. The development of such dual-specificity vectors for targeting cancer cells is an attractive and potentially safer and more efficacious way of delivering drugs. We provide examples of this approach for delivering brain cancer therapeutics, using a specific biomarker on glioblastoma tumor cells. PMID- 22671768 TI - Getting stuck in depression: the roles of rumination and emotional inertia. AB - Like many other mental disorders, depression is characterised by psychological inflexibility. Two instances of such inflexibility are rumination: repetitive cognitions focusing on the causes and consequences of depressive symptoms; and emotional inertia: the tendency for affective states to be resistant to change. In two studies, we tested the predictions that: (1) rumination and emotional inertia are related; and (2) both independently contribute to depressive symptoms. We examined emotional inertia of subjective affective experiences in daily life among a sample of non-clinical undergraduates (Study 1), and of affective behaviours during a family interaction task in a sample of clinically depressed and non-depressed adolescents (Study 2), and related it to self reported rumination and depression severity. In both studies, rumination (particularly the brooding facet) and emotional inertia (particularly of sad/dysphoric affect) were positively associated, and both independently predicted depression severity. These findings demonstrate the importance of studying both cognitive and affective inflexibility in depression. PMID- 22671769 TI - Psychometric properties of the Swedish version of the selection, optimization, compensation questionnaire. AB - BACKGROUND: The model of selection, optimization and compensation has been proposed as a model of adaptive management strategies throughout the lifespan. AIM: The aim of this study was to test the psychometric properties of a translated Swedish version of the 12-item selection, optimization, and compensation (SOC) questionnaire. METHOD: The 12-item SOC questionnaire is composed of four subscales: elective selection (ES), loss-based selection, optimization and compensation. A convenience sample of 122 Swedish-speaking people, aged 19-85, participated in a study of the validity and reliability of the SOC questionnaire. Cronbach's alpha coefficient, corrected item-total correlation and Cronbach's alpha if item deleted were used for reliability testing. Two other scales, the ways of coping questionnaire and Rosenberg's self esteem scale, were used to test convergent validity, and the geriatric depression scale was used to test discriminant validity. Stability over time was evaluated using a test-retest model with a 2-week interval. RESULTS: The 12-item SOC questionnaire showed a Cronbach's alpha value of 0.50, and the subscales ranged from alpha = 0.16 to alpha = 0.64. Two items in the ES subscale had negative values on the corrected item-total correlation and showed substantial improvement (>0.05) in Cronbach's alpha when item deleted. When these two items that influenced internal consistency were deleted, Cronbach's alpha rose to 0.68. CONCLUSION: The Swedish version of the 12-item SOC questionnaire showed deficiencies in a test of internal consistency because of two items in the ES subscale, and these two items were deleted. A consequence of the reduction is a weakening of the ES subscale and thereby to some extent the SOC questionnaire in total. Further testing is advisable. However, the 10-item SOC questionnaire was acceptable in a test of validity and reliability. PMID- 22671770 TI - Antimicrobial activity of whey protein isolate edible films with essential oils against food spoilers and foodborne pathogens. AB - The use of antimicrobial edible film is proposed as a means of improving food safety and extending the shelf-life of food systems by controlling the release of antimicrobials on food surfaces. In this work we first selected and studied 8 different essential oils (EOs) from plants, namely, oregano, clove, tea tree, coriander, mastic thyme, laurel, rosemary, and sage as natural antimicrobials against 2 gram-positive bacteria (Listeria innocua and Staphylococcus aureus) and 2 gram-negative bacteria (Salmonella enteritidis and Pseudomona fragi) by using the agar disk diffusion method. EOs from oregano, clove, and tea tree produced the largest surfaces of inhibition against the growth of the 4 bacterial strains tested. Second and following the assessment of compatibility, stable antimicrobial edible films based on whey protein isolate (WPI) with increasing concentrations (0.5% to 9%) of the 8 EOs were developed and tested for antimicrobial activity against the same gram-positive and gram-negative bacteria. WPI-edible films incorporating oregano or clove EO were found to have the most intense inhibitory effect of microbial growth. The bacterial strain gram-negative P. fragi presented the less susceptibility to the effect of those films. Moreover, only the edible films based on these 2 EOs were active against all 4 studied microorganisms. On the other hand, the edible films incorporating tea tree, coriander, mastic thyme, laurel, rosemary, or sage EOs even at high concentrations (7% to 9%) did not cause any antimicrobial effect against the pathogens S. aureus or S. enteritidis. PRACTICAL APPLICATION: Potential applications of this technology can introduce direct benefits to the food industry by improving safety and microbial product quality. The results of this research have direct application in the food industry with potential applications in various foodstuffs, including meat and poultry products where the control of spoilage bacteria such as P. fragi throughout their chilled storage or the improvement of food safety by controlling pathogens such as S. enteritidis are topics of particular interest for the industry. PMID- 22671767 TI - Recommendations and considerations for the use of biologics in orthopedic surgery. AB - Reconstruction of extensive bone defects remains technically challenging and has considerable medical and financial impact on our society. Surgical procedures often require a bone/substitute graft to enhance and accelerate bone repair. Bone autografts are associated with morbidity related to bone harvesting and are limited in quantity. Alternatively, bone allografts expose the patient to the risk of transmission of infectious disease. Synthetic bone graft substitutes, such as calcium sulfates, hydroxyapatite, tricalcium phosphate, and combinations, circumvent some of the disadvantages of auto- and allografts, but have limited indications. Biomedical research has made possible the stimulation of the body's own healing mechanisms, either by delivering exogenous growth factors locally, or by stimulating their local production by gene transfer. Among all known factors having osteoinductive properties, only two bone morphogenetic proteins (for specific indications) and demineralized bone matrix have been approved for clinical use. In addition, ongoing research is exploring the efficacy of cell therapy and tissue engineering. The present report examines the composition, biological properties, indications, clinical experience and regulations of several of the biotherapeutics employed for bone reconstruction. PMID- 22671771 TI - Prospective analysis of factors related to migraine aura--the PAMINA study. AB - OBJECTIVES: The aim of this study was to examine factors increasing and decreasing the risk of occurrence of migraine aura and of headache and migraine not associated with aura (HoA, MoA) prospectively by means of a daily diary. METHODS: Of 327 patients with migraine completing a comprehensive diary up to 90 days, we selected all patients who recorded at least 1 episode of migraine aura. To find risk indicators and triggers of aura, HoA, and MoA, we analyzed 56 variables and calculated univariate and multivariate generalized linear mixed models. RESULTS: Fifty-four patients recorded a total of 4562 patient days including 354 days with migraine aura. In the multivariate analysis, the risk of aura was statistically significantly increased by smoking, menstruation, and hunger, and it was decreased by holidays and days off. The risk of HoA and/or MoA was increased during menstruation, by psychic tension, tiredness, and odors, and it was decreased by smoking. CONCLUSION: Menstruation is the most prominent factor increasing the risk of aura as well as that of HoA and MoA. Smoking shows the most striking difference increasing the risk of aura, but decreasing the risk of HoA and MoA. PMID- 22671772 TI - Acute morbidity and mortality in invertebrates and fish following exposure to potassium-deficient saltwater. PMID- 22671774 TI - A novel HLA-B*54 allele, B*54:25, identified by sequence-based typing. AB - The novel allele B*54:25 allele showed a single nucleotide difference with B*54:01:01 at nt 208 C > G in exon 2. PMID- 22671773 TI - Protection of dopaminergic cells by urate requires its accumulation in astrocytes. AB - Urate is the end product of purine metabolism and a major antioxidant circulating in humans. Recent data link higher levels of urate with a reduced risk of developing Parkinson's disease and with a slower rate of its progression. In this study, we investigated the role of astrocytes in urate-induced protection of dopaminergic cells in a cellular model of Parkinson's disease. In mixed cultures of dopaminergic cells and astrocytes oxidative stress-induced cell death and protein damage were reduced by urate. By contrast, urate was not protective in pure dopaminergic cell cultures. Physical contact between dopaminergic cells and astrocytes was not required for astrocyte-dependent rescue as shown by conditioned medium experiments. Urate accumulation in dopaminergic cells and astrocytes was blocked by pharmacological inhibitors of urate transporters expressed differentially in these cells. The ability of a urate transport blocker to prevent urate accumulation into astroglial (but not dopaminergic) cells predicted its ability to prevent dopaminergic cell death. Transgenic expression of uricase reduced urate accumulation in astrocytes and attenuated the protective influence of urate on dopaminergic cells. These data indicate that urate might act within astrocytes to trigger release of molecule(s) that are protective for dopaminergic cells. PMID- 22671776 TI - Enhanced life-role participation in response to comprehensive gait training in chronic stroke survivors. AB - PURPOSE: Intensive gait training can produce improvements in gait and function (> 6 months after stroke); findings are mixed for enhanced life role participation. Therefore, it is unclear if improved gait and function translate into life role participation gain. Our objective was to evaluate whether intensive gait therapy can produce significant improvements in life role participation for chronic stroke survivors. METHODS: In conjunction with a clinical gait training trial, we conducted a secondary analysis for a 44-member cohort with stroke (>6 months). Gait training interventions included exercise, body weight supported treadmill training (BWSTT), over-ground gait training, and functional electrical stimulation (FES) for 1.5 h/day, 4 days/wk for 12 weeks. Study measures included Tinetti Gait (TG) (gait impairment), Functional Independence Measure (FIM, function), Stroke Impact Scale Subscale of Life Role Participation (SISpart), and Craig Handicap Assessment & Reporting Technique (CHART, life-role participation). Analyses included Wilcoxon Signed Rank Test and PLUM Regression Model. RESULTS: Gait interventions produced significant improvement in CHART (p = 0.020), SISpart (p = 0.011), FIM (p < 0.0001), and Tinetti Gait (p < 0.0001). Age, gender and time since stroke did not predict response to treatment. CONCLUSIONS: Intensive, multi-modal, long-duration gait therapy resulted in significant gain in life-role participation, according to a relatively comprehensive, homogeneous measure. PMID- 22671777 TI - In vitro metabolism of piperaquine is primarily mediated by CYP3A4. AB - Piperaquine (PQ) is part of a first-line treatment regimen for Plasmodium falciparum malaria recommended by the World Health Organization (WHO). We aimed to determine the major metabolic pathway(s) of PQ in vitro. A reliable, validated tandem mass spectrometry method was developed. Concentrations of PQ were measured after incubation with both human liver microsomes (HLMs) and expressed cytochrome P450 enzymes (P450s). In pooled HLMs, incubations with an initial PQ concentration of 0.3 uM resulted in a 34.8 +/- 4.9% loss of substrate over 60 min, corresponding to a turnover rate of 0.009 min(-1) (r(2) = 0.9223). Miconazole, at nonspecific P450 inhibitory concentrations, resulted in almost complete inhibition of PQ metabolism. The greatest inhibition was demonstrated with selective CYP3A4 (100%) and CYP2C8 (66%) inhibitors. Using a mixture of recombinant P450 enzymes, turnover for PQ metabolism was estimated as 0.0099 min( 1); recombinant CYP3A4 had a higher metabolic rate (0.017 min(-1)) than recombinant CYP2C8 (p < .0001). Inhibition of CYP3A4-mediated PQ loss was greatest using the selective inhibitor ketoconazole (9.1 +/- 3.5% loss with ketoconazole vs 60.7 +/- 5.9% with no inhibitor, p < .0001). In summary, the extent of inhibition of in vitro metabolism with ketoconazole (83%) denotes that PQ appears to be primarily catalyzed by CYP3A4. Further studies to support these findings through the identification and characterization of PQ metabolites are planned. PMID- 22671778 TI - Prediction of clearance and volume of distribution in the obese from normal weight subjects: an allometric approach. AB - BACKGROUND AND OBJECTIVE: The principles of allometry can be applied within a given species (intra-species scaling), for example extrapolation of pharmacokinetic parameters from adults to adolescents and older children (>5 years of age). Similarly, allometric scaling may also be used to predict pharmacokinetic parameters from normal weight subjects to the obese. The objective of this investigation was to evaluate the predictive performance of several allometric methods for the prediction of drug clearance (CL) and volume of distribution (V(d)) in the obese from normal weight subjects. METHODS: CL and V(d) values for 12 drugs for obese and normal weight subjects were obtained from the literature. Three methods (simple allometry and fixed exponents of 0.75 and 1.0) and two methods (simple allometry and a fixed exponent of 1.0) were used to predict CL and V(d), respectively, using total body weight in the obese from normal weight subjects. When data were available, ideal body weight, percentage ideal body weight and body mass index were also used for prediction purposes. RESULTS: The results of the study indicated that CL could be predicted with accuracy in the obese from normal weight subjects using total body weight and simple allometry as well as fixed exponent of 0.75. The prediction of V(d) in the obese from normal weight subjects was less accurate than the prediction of CL in this population. For the prediction of CL and V(d) in the obese, simple allometry performed better than the fixed exponent of 0.75 or 1.0, respectively. CONCLUSIONS: The study indicated that allometric scaling can be applied to predict CL in the obese from normal weight subjects with high accuracy. The predicted CL can then be used to select a dose to initiate a clinical trial (pharmacokinetics, safety and efficacy). PMID- 22671779 TI - The anti-nausea effects of CB1 agonists are mediated by an action at the visceral insular cortex. AB - BACKGROUND AND PURPOSE: Conditioned gaping reactions reflect nausea-induced behaviour in rats. Cannabinoid 1 receptor (CB(1) ) agonists interfere with the establishment of nausea-induced conditioned gaping; however, it is not known if their effects are mediated by an action at peripheral or central CB(1) receptors. EXPERIMENTAL APPROACH: We utilized the conditioned gaping model of nausea to evaluate the effect of peripheral and central administration of the peripherally restricted CB(1) agonist, CB13, on the establishment of LiCl-induced gaping in rats. We further evaluated the ability of HU-210 administered to the gustatory insular cortex (GIC) or visceral insular cortex (VIC) to interfere with LiCl induced conditioned gaping and determined if this effect was mediated by CB(1) receptors. KEY RESULTS: Central, but not peripheral, CB13 suppressed LiCl-induced conditioned gaping. Central administration of the potent CB(1) agonist, HU-210, delivered to the VIC, but not the GIC, suppressed the establishment of LiCl induced gaping reactions, but not LiCl-induced suppression of hedonic reactions or conditioned taste avoidance. This pattern of results suggests that HU-210 delivered to the VIC prevented LiCl-induced nausea, but not learning per se. The suppression of LiCl-induced conditioned gaping by HU-210 was mediated by CB(1) receptors because it was prevented by co-administration of CB(1) antagonist/inverse agonist, AM-251, into the VIC. A high dose of AM-251 (20 ug) administered alone into the VIC did not produce conditioned gaping reactions. CONCLUSIONS AND IMPLICATIONS: The nausea-relieving effects of CB(1) agonists, but not the nausea-inducing effects of CB(1) inverse agonists, are mediated, at least in part, by their action at the VIC in rats. PMID- 22671853 TI - The role of noncoronary cusp ablation approach in the treatment of perinodal atrial tachycardias. AB - BACKGROUND: Ablation in the noncoronary aortic cusp (NCC) potentially has a role in the treatment of perinodal atrial tachycardias (ATs). The objective of the study was to characterize clinical and electrophysiological properties of perinodal ATs between two groups of requiring and not requiring NCC ablation. METHODS: A total of 113 patients with focal ATs who underwent electrophysiologic study and radiofrequency catheter ablation were enrolled in the study. The clinical and electrophysiological characteristics of ATs that need and not need NCC ablation were compared. RESULTS: Totally 20 cases were revealed to have the focal ATs located in the perinodal area. Among them, only five cases (25%) warrant ablation in the NCC, whereas the remainder could be successfully eliminated by ablation from the endocardial right atrium at the perinodal region. There were no clinical and electrophysiological clues observed to have the potential to predict the true original site, including the activation mode, the three-dimensional mapping characteristics of earliest activation site in the right atrium, as well as the time of termination during the ablation in the perinodal area. CONCLUSIONS: Approximately, one-fourth of the perinodal ATs warrant ablation in the NCC. However, no clinical and electrophysiological clues could predict the potential site of the perinodal ATs. PMID- 22671854 TI - Anger as "seeing red": evidence for a perceptual association. AB - Metaphor representation theory contends that people conceptualise their non perceptual states (e.g., emotion concepts) in perceptual terms. The present research extends this theory to colour manipulations and discrete emotional representations. Two experiments (N = 265) examined whether a red font colour would facilitate anger conceptions, consistent with metaphors referring to anger to "seeing red". Evidence for an implicit anger-red association was robust and emotionally discrete in nature. Further, Experiment 2 examined the directionality of such associations and found that they were asymmetrical: Anger categorisations were faster when a red font colour was involved, but redness categorisations were not faster when an anger-related word was involved. Implications for multiple literatures are discussed. PMID- 22671855 TI - Is it that difficult to find a good preference order for the incremental algorithm? AB - In a recent article published in this journal (van Deemter, Gatt, van der Sluis, & Power, 2012), the authors criticize the Incremental Algorithm (a well-known algorithm for the generation of referring expressions due to Dale & Reiter, 1995, also in this journal) because of its strong reliance on a pre-determined, domain dependent Preference Order. The authors argue that there are potentially many different Preference Orders that could be considered, while often no evidence is available to determine which is a good one. In this brief note, however, we suggest (based on a learning curve experiment) that finding a Preference Order for a new domain may not be so difficult after all, as long as one has access to a handful of human-produced descriptions collected in a semantically transparent way. We argue that this is due to the fact that it is both more important and less difficult to get a good ordering of the head than of the tail of a Preference Order. PMID- 22671856 TI - Peracetic acid is effective for controlling fungus on channel catfish eggs. AB - Peracetic acid (PAA) is a relatively new compound suggested for use to treat pathogens in aquaculture. It is approved for use in Europe, but not in the United States. This study determined the effectiveness of PAA for fungus control on channel catfish, Ictalurus punctatus (Rafinesque), eggs. The study consisted of five PAA concentrations (2.5, 5, 10, 15 and 20mgL(-1) ) and an untreated control in a flow-through system. A single spawn was used for each replication (N =4). Eggs were treated twice daily until the embryos developed eyes. When hatching was complete for all viable eggs, fry were counted to determine the percent survival in each treatment. Fungal growth was severe in the untreated controls resulting in 11% survival. Treatments of 2.5, 5 and 10mgL(-1) PAA were significantly different from the controls (P<0.05). The highest percent survival of hatched fry was with 5mgL(-1) PAA administered twice daily; the 2.5mgL(-1) PAA treatment had slightly less survival, but gives a higher margin of safety in case of treatment error. Very little fungus was present in treatments receiving 2.5mgL(-1) PAA or higher, and concentrations of 15 and 20mgL(-1) PAA were toxic to the eggs. The mean survivals in the 0, 2.5, 5, 10, 15 and 20mgL(-1) PAA treatments were 11%, 60%, 63%, 62%, 32% and 0%, respectively. Therefore, PAA may be a compound that merits further investigations regarding its use in U.S. aquaculture. PMID- 22671857 TI - Pathogenesis of migraine: role of neuromodulators. AB - The pathogenesis of migraine is still, today, a hotly debated issue. Recent biochemical studies report the occurrence in migraine of metabolic abnormalities in the synthesis of neurotransmitters and neuromodulators. These include a metabolic shift directing tyrosine metabolism toward the decarboxylation pathway, therein resulting in an unphysiological production of noradrenaline and dopamine along with increased synthesis of traces amines such as tyramine, octopamine, and synephrine. This biochemical alteration is possibly favored by impaired mitochondrial function and high levels of glutamate in the central nervous system (CNS) of migraine patients. The unbalanced levels of the neurotransmitters (dopamine and noradrenaline) and neuromodulators (eg, tyramine, octopamine, and synephrine) in the synaptic dopaminergic and noradrenergic clefts of the pain matrix pathways may activate, downstream, the trigeminal system that releases calcitonin gene-related peptide. This induces the formation of an inflammatory soup, the sensitization of first trigeminal neuron, and the migraine attack. In view of this, we propose that migraine attacks derive from a top-down dysfunctional process that initiates in the frontal lobe in a hyperexcitable and hypoenergetic brain, thereafter progressing downstream resulting in abnormally activated nuclei of the pain matrix. PMID- 22671859 TI - Potential role of alpha-synuclein in neurodegeneration: studies in a rat animal model. PMID- 22671858 TI - Physicochemical properties and antioxidant activities of Korean traditional alcoholic beverage, yakju, enriched with mulberry. AB - Mulberry fruits (Morus alba L.), rich in health beneficial compounds such as polyphenols, flavonoids, and anthocyananis, have traditionally been used as nutritional foodstuffs and fork medicines. In this study, physicochemical properties and antioxidant activities of a traditional Korean alcoholic beverage ''yakju'' enriched with mulberry were evaluated. The beverage was enriched with smoothies prepared from Korean mulberry cultivars of Cheongilppong (CP), Suwonppong (SP), and Daesungppong (DP). In comparison to the control, an increase in alcohol content and total acidity and a decrease in sugar level in yakju enriched with mulberry were observed during 15 d of fermentation. The total polyphenol and total flavonoid content increased in the following order: DP yakju > SP yakju > CP yakju > control yakju. In contrast, the anthocyanin content decreased during the fermentation periods. The trans-resveratrol content of mulberry yakju increased during the fermentation and the resveratrol content of DP yakju (0.24 mg/L) was significantly higher than that of SP yakju (0.21 mg/L) and CP yakju (0.14 mg/L) on the 15th day of fermentation (P < 0.05). The antioxidant activities of mulberry yakju, which was assessed using the 1,1 diphenyl-2-picryl hydrazyl (DPPH), 2,2'-azino-bis-(3-ethylbenozothiazoline-6 sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP), and reducing power assays, decreased during the 1st day of fermentation and increased into thereafter. The increase in antioxidant activities of mulberry yakju might have been affected primarily by the total flavonoid and total polyphenol content with increasing alcohol concentration, as a good extractor, during the fermentation; however, the antioxidant activities may have also been affected by the total anthocyanin content up to the 1st day of fermentation. PRACTICAL APPLICATION: The physicochemical properties and antioxidant activities of a traditional Korean alcoholic beverage ''yakju'' enriched with mulberry were investigated. This analysis is important for the potential applications of mulberry yakju as functional alcoholic drinks. PMID- 22671860 TI - A novel HLA-B*35 allele, B*35:188, identified by sequence-based typing. AB - The novel allele B*35:188 allele showed a single nucleotide difference with B*35:96 at nt 347 T>C in exon 3. PMID- 22671861 TI - The reliability and validity of the World Health Organization Disability Assessment Schedule (WHODAS-II) in stroke. AB - PURPOSE: Psychometric properties of the World Health Organization Disability Assessment Schedule (WHODAS-II) in stroke have received some attention recently, mostly using classical approaches, but there is still an absence of investigation from a modern psychometric perspective. This study aimed to test the reliability and validity of the WHODAS-II in stroke, using modern psychometric analysis. METHODS: A total of 188 community-dwelling poststroke patients were recruited. Internal construct validity was assessed by Rasch analysis, reliability by internal consistency and person separation index (PSI), and external construct validity by associations with Functional Independence Measure (FIM(TM)). RESULTS: Rasch analysis indicated that total score (based upon 32 items, omitting the work related items) was satisfactory, after adjustment for local dependency. The proposed "activities" and "participation" components also satisfied Rasch model expectations. An existing short form was problematic due to inclusion of a work related item, but an alternative 10-item version was acceptable. Cronbach's alpha for the WHODAS-II, its domains and components varied between 0.83 and 0.99 and PSI between 0.70 and 0.95. External construct validity was confirmed by expected correlations with FIM(TM). CONCLUSIONS: WHODAS-II provides a reliable and valid instrument for measuring disability and components of "activities" and "participation" in stroke survivors. Various combinations of the item set may provide a range of scales to suit most research needs. PMID- 22671862 TI - Metabolic map and bioactivation of the anti-tumour drug noscapine. AB - BACKGROUND AND PURPOSE: Noscapine is a promising anti-tumour agent. The purpose of the present study was to describe the metabolic map and investigate the bioactivation of noscapine. EXPERIMENTAL APPROACH: Ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry-based metabolomics was used to analyse the in vitro incubation mixtures, urine and faeces samples from mice treated with noscapine. Recombinant drug-metabolizing enzymes were employed to identify those involved in noscapine metabolism. Hepatic GSH levels and serum biochemistry were also carried out to determine reactive metabolites of noscapine. KEY RESULTS: Several novel phase I metabolites of noscapine were detected after oral gavage of mice, including an N demethylated metabolite, two hydroxylated metabolites, one metabolite undergoing both demethylation and cleavage of the methylenedioxy group and a bis demethylated metabolite. Additionally, several novel glucuronides were detected, and their structures were elucidated through MS/MS fragmentology. Recombinant enzymes screening showed the involvement of several cytochromes P450, flavin containing mono-oxygenase 1 and the UDP-glucuronosyltransferases UGT1A1, UGT1A3, UGT1A9 and UGT2B7, in noscapine metabolism. In vitro glutathione trapping revealed the existence of an ortho-quinone reactive intermediate formed through further oxidation of a catechol metabolite. However, this bioactivation process of noscapine does not occur in vivo. Similar to this result, altered glutathione levels in liver and serum biochemistry revealed no evidence of hepatic damage, thus indicating that, at least in mice, noscapine does not induce hepatotoxicity through bioactivation. CONCLUSIONS AND IMPLICATIONS: A comprehensive metabolic map and bioactivation evaluation provides important information for the development of noscapine as an anti-tumour drug. PMID- 22671864 TI - Analysis of event logs from syringe pumps: a retrospective pilot study to assess possible effects of syringe pumps on safety in a university hospital critical care unit in Germany. AB - BACKGROUND: Medication errors occur in approximately one out of five doses in a typical hospital setting. Patients in the intensive care unit (ICU) are particularly susceptible to errors during the application of intravenous drugs as they receive numerous potent drugs applied by syringe pumps. OBJECTIVE: The aim of this study was to analyse the effects on potential harmful medication errors and to address factors that have potential for improving medication safety after the introduction of a standardized drug library into syringe pumps with integrated decision support systems. METHODS: A team of physicians and nurses developed a dataset that defined standardized drug concentrations, application rates and alert limits to prevent accidental overdosing of intravenous medications. This dataset was implemented in 100 syringe pumps with the ability to log programming errors, alerts, reprogramming events and overrides ('smart pumps'). In this retrospective pilot study, all pump-related transaction data were obtained from the pump logs, by downloading the data from the pumps, covering 20 months of use between 1 April 2008 and 30 November 2009. Patient data were gathered from the electronic patient charts. The study was performed in a cardiothoracic ICU of the Charite University Hospital, Berlin, Germany. RESULTS: A total of 7884 patient treatment days and 133,601 infusion starts were evaluated. The drug library with the features of the dose rate was used in 92.8% of the syringe pump starts, in 1.5% of the starts a manual dosing mode without the use of the drug library was used and in 5.7% of the starts the mode 'mL/h', without any calculation features, was used. The most frequently used drugs were vasoactive drugs, followed by sedation medication. The user was alerted for a potentially harmful overdosing in 717 cases and in 66 cases the pumps were reprogrammed after the alert. During the early morning hours a higher rate of alarms was generated by the pumps, compared with the rest of the day. CONCLUSIONS: Syringe pumps with integrated safety features have the capacity to intercept medication errors. The structured evaluation of the bedside programming history in log recordings is an important benefit of smart pumps, as this enables the users to obtain an objective measurement of infusion practice, which can be used to provide team feedback and to optimize the programming of the pumps. Further research will show if the combination of these data with physiological data from ICU patients can improve the safety of pump-driven intravenous medication. PMID- 22671865 TI - The safety of H1N1 vaccine in children in Saudi Arabia: a cohort study using modern technology in a developing country. AB - BACKGROUND: With its rapid introduction in 2009, concerns about the safety of the H1N1 vaccines have been raised. Data were especially limited on the pediatric safety of H1N1 vaccine in Saudi Arabia. OBJECTIVES: The objectives of this study were to investigate the safety of the H1N1 vaccine (Pandemrix((r))) in children and examine the feasibility of obtaining information on possibly associated adverse reactions using mobile telephone contact with child caregivers. METHODS: A cohort study was conducted in Riyadh, Saudi Arabia. Patients were included if they were aged between 6 and 18 years and had received one dose of the H1N1 vaccine. A control group involved children from the same school system who had not received the vaccine. Six months following vaccination, a clinical pharmacist called the caregiver of the child to ask about hospitalization, emergency room visits and events related to H1N1 vaccine administration using a standardized questionnaire. RESULTS: Caregivers of 372 school-age children were contacted. The response rate was 97% (n = 359). A total of 169 children who received at least one dose of the H1N1 vaccine were compared with 190 children in the control group who had not received the vaccine. Controlling for age, sex, education and use of medications, the odds ratio (OR) of hospitalization or emergency room visits for children within the 6 months after vaccination relative to the unvaccinated children was 1.25 (95% CI 0.47, 3.35). The risk of influenza-like symptoms was significantly reduced in vaccinated children compared with unvaccinated children (OR 0.63; 95% CI 0.41, 0.99). CONCLUSION: School-age children in Saudi Arabia who received the H1N1 vaccine did not have an increased risk of hospitalization or emergency room visits. Larger studies are needed to confirm these results. Proactive pharmacovigilance is important in assessing the safety of vaccines and other medications. It is feasible to collect information on adverse drug reactions using mobile telephones, a method that can be of benefit in both developed and developing countries. PMID- 22671905 TI - The Three-Dimensional NMR Solution Structure of alpha-Cobratoxin at pH 7.5 and Conformational Differences With the NMR Solution Structure at pH 3.2. AB - Abstract The 3D solution structure of alpha-cobratoxin, a neurotoxin purified from the Naja naja siamensis snake venom, has been determined by Nuclear Magnetic Resonance spectroscopy, in conjunction with distance geometry and restrained molecular dynamics, at pH 7.5. A total of 490 distance restraints were obtained from NOE intensities and 25 phi dihedral angle restraints deduced from J- coupling data. The generated structures are well defined with root mean square deviations from a geometrical mean structure of 0.107 +/- 0.036 nm for the backbone atoms and 0.128 +/-0.073 nm for the side-chain atoms (considering residues 1 to 66 minus 26 to 35). A comparison between the generated structures at pH 7.5 and the mean NMR solution structure at pH 3.2 revealed that the 3D structure of alpha-cobratoxin is more compact at neutral pH. This major difference is mainly due to the pH-dependant conformational variations of three residues His(18), Thr(44) and Thr(59). PMID- 22671904 TI - Autobiographical memory specificity and the persistence of depressive symptoms in HIV-positive patients: rumination and social problem-solving skills as mediators. AB - Individuals infected with human immunodeficiency virus (HIV) are at elevated risk for depressive conditions, which in turn can negatively impact health-related behaviours and the course of illness. The present study tested the role of autobiographical memory specificity and its interaction with perceived stress in the persistence of depressive symptoms among dysphoric HIV-positive individuals. Additionally, we examined whether rumination and social problem solving mediated these effects. Results indicated that memory specificity moderated the impact of perceived stress, such that perceived stress was more strongly associated with follow-up depressive symptoms among those with greater memory specificity. Rumination, but not social problem solving, mediated this effect. Implications of these findings are discussed. PMID- 22671906 TI - Molecular Dynamics Simulation of Equine Infectious Anemia Virus Tat Protein in Water and in 40% Trifluoroethanol. AB - Abstract Two molecular dynamics (MD) simulations were performed in order to increase the understanding of the dependence of protein conformation on solvent environment. The protein used for these simulations is the transcriptional activator of the equine infectious anemia virus (EIAV-Tat). The structure of this protein has been determined by nuclear magnetic resonance (NMR) in aqueous solution (Willbold et al., Science 264, 1584 (1994)) and in 40% (v/v) trifluoroethanol (TFE) (Sticht et al., Eur. J. Biochem., submitted) showing considerable differences in the stability of the secondary structure elements. In order to investigate the influence of the solvent MD simulations (300 K; 200 ps) were carried out in water and in a solvent containing 40% (v/v) TFE. In both simulations the structure as determined in 40% TFE by NMR, showing three-helices and a tight type II turn, was used as the initial structure. The MD simulations clearly indicate a decreased stability of the secondary structure elements in aqueous environment as made obvious by larger atomic motions and stronger fluctuations in the length of the hydrogen bonds. Complete unfolding of the helices was not observed on a 200 ps timescale. The root mean square deviation (RMSD) values of the backbone atoms after 200 ps simulation compared to the starting structure underline the strong influence of the solvent on the protein stability. This RMSD value is 1.95 A for the simulation in water and 1.29 A for the simulation in TFE/water. This result supports the notion that TFE acts as a secondary structure inducing and stabilizing solvent. The differences apparent from the MD simulations are in good agreement with the data derived from NMR measurements, showing the relevance of MD as a method for estimating conformational and dynamical properties of proteins. PMID- 22671907 TI - A Full-Coordinate Model of the Polymerase Domain of HIV-I Reverse Transcriptase and its Interaction With a Nucleic Acid Substrate. AB - Abstract We present a full-coordinate model of residues 1-319 of the polymerase domain of HIV-I reverse transcriptase. This model was constructed from the x-ray crystallographic structure of Jacobo-Molina et al. (Jacobo-Molina et al., P.N.A.S. USA 90, 6320-6324 (1993)) which is currently available to the degree of C- coordinates. The backbone and side-chain atoms were constructed using the MAXSPROUT suite of programs (L. Holm and C. Sander, Mol. Biol. 218, 183-194 (1991)) and refined through molecular modeling. A seven base pair A-form dsDNA was positioned in the nucleic acid binding cleft to represent the template-primer complex. The orientation of the template-primer complex in the nucleic acid binding cleft was guided by the positions of phosphorus atoms in the crystal structure. Two magnesium ions were placed in the active site in order to better understand the polymerization mechanism. The positions of metal ions in a number of structures guided the placement of ions in this study (L.S. Beese and T.A. Steitz, EMBO. J10, 25-33 (1991); T.A. Steitz and J.A. Steitz, P.N.A.S. USA 90, 6498-6502 (1993); D.L. Sloan et al., J. Biol. Chem. 250, 8913-8920 (1975); R.F. Setlik et al., J. Biomol. Str. Dyn. 10, 945-972 (1993)). The geometry of the active site allowed metal ions to be bound to Asp 110 and Asp 186 of the catalytic triad. However, due to spacial constraints, Asp 185 was found unable to bind to a metal ion. Due to its proximity to the attacking 3'OH group of the 3' terminal residue of the primer strand, it is proposed that this residue acts as a general base which abstracts a proton from the attacking group. Based on the locations of these metal ions with respect to the attacking group of the 3' end of the primer strand and to an incoming dTTP placed in the active site, we propose roles for the magnesium ions and discuss a mechanism through which chain elongation occurs. Also reported are the interactions between the polymerase domain and the template-primer complex observed in our model. These interactions are discussed in view of their possible roles in positioning the nucleic acid complex in the binding cleft and in regard to other structural and functional roles. The importance of these residues as observed in our model is compared to results from multiple sequence alignments and various mutational studies on HIV-I reverse transcriptase. PMID- 22671908 TI - Application of 3-Dimensional Homology Modeling of Cytochrome P450 2B1 for Interpretation of Site-Directed Mutagenesis Results. AB - Abstract Three-dimensional structures of cytochrome P450 2B1 were modeled based on the crystallographic structure of P450(cam). The effect of the alignment, loop choice, and minimization with or without water was assessed. Although final models were similar in overall structure, the identity of active site residues depended upon the alignment. An example is Phe-206, which may or may not form part of the active site. The choice of the loop conformation had a lesser effect, while including water in the final minimization step was essential for preserving the shape and size of the active site. The best model (model 2) was in good agreement with the data from site-directed mutagenesis studies, and correctly predicted the effect of substitutions at 9 out of 10 amino acid positions. Thus, residues important for P450 2B1 activity, such as Ile- 114, Phe-206, Ile-290, Thr 302, Val-363, and Gly-478, constitute part of the active site and are able to interact with the substrate androstenedione through hydrophobic interactions. On the other hand, Ser-303, Ser-360 and Lys-473 are far from the active site and/or cannot interact with the substrate, in agreement with experimental data. The model indicates other residues likely to be important for enzyme function, such as Tyr- 111, Leu-209, Ile-477, and Ile- 480, which can be tested experimentally. The substrate may assume numerous binding orientations consistent with observed patterns of hydroxylation at C(5) and C(6). The replacement in the model of certain amino acid residues to mimic residue substitutions from site-directed mutagenesis studies and docking of the substrate into the modified active site allowed a plausible explanation for alterations in regio- and stereospecificities of some mutants of P450 2B1, such as Gly-478 -> Ala or Val-363 Ala. PMID- 22671909 TI - Characterization of the Structural Conformation Adopted by (TTAGGG)(n) Telomeric DNA Repeats of Different Length in Closed Circular DNA. AB - Abstract Telomeric DNA sequences are known to adopt unusual DNA structures upon protonation when contained into negatively supercoiled DNA. In this paper, the structural properties of (T(2)AG(3))(n) telomeric sequences of different length is analyzed in detail. Transition to the protonated form is observed at very low pH for (T(2)AG(3))(n<8) sequences. Formation of the protonated form is facilitated by negative supercoiling. The patterns of chemical modification obtained with different chemical reagents indicate that protonation induces denaturation of the (T(2)AG(3))(n) telomeric sequences. Upon denaturation, the "C rich" strand becomes structured forming, most likely, hairpin-like conformations stabilized by the formation of C(+).C pairs and, probably, of A(+).A pairs. The "G-rich" strand of the (T(2)AG(3))(8) sequence shows also signs of becoming structured giving rise to various structural conformers which might include triple- and tetra-stranded conformations. However, in the case of shorter sequences, the "G-rich" strand remains basically single-stranded. PMID- 22671910 TI - Theoretical Design, Chemical Synthesis and Footprinting Analysis of a Novel Peptide Derivative of the Intercalator 7-H Pyridocarbazole Targeted Towards the Major Groove of DNA. AB - Abstract In order to target the major groove of DNA, we have designed novel peptide derivatives of 7-H pyridocarbazole, which is the chromophoric ring of ditercalinium, a potent antitumor bisin- tercalator. We will present here the results obtained with a compound that has a D-Asn tethered to the pyridinium nitrogen of the ring by a protonated beta-alanyl-ethyl chain. We have investigated two alternative means of intercalation of the chromophore: first, into the (pur-pur) sequences, d(CpG)(2) and d(CpA).d(TpG); second, into the (pur pyr) sequences, d(GpC)(2)and d(GpT).d(ApC). For the first intercalative mode, the best bound triplet sequences are d(ACG).d(CGT) and d(ACA) d(TGT), namely with an adenine immediately upstream from the intercalation site. In these complexes, the chromophore has its concave side in the major groove, its long axis nearly colinear with the mean long axis of the two base pairs of the intercalation site, and a bidentate H-bonded configuration occurs which involves the C=0 and NH groups of the D-Asn side chain and HN(6) and N(7) (resp.) of the adenine base upstream. One alkylammonium proton is H-bonded to N(7) of the guanine of the intercalation site, on the strand opposite to the one bearing the adenine. In the second intercalative mode, the chromophore's concave site now faces one DNA strand, and both alkylammonium protons are involved in H-bonds with N(7) and O(6) of the 3' guanine on the same strand. The peptide's complexes with sequences having A, G, or C upstream of this guanine were computed to be energetically competitive with those with the best (pyr-pur) triplets. This provides a rare example of energetically favourable drug intercalation in-between (pur-pyr) sequences as compared to the standard (pyr-pur) ones. The synthesis of this compound was performed, and a series of footprinting experiments undertaken on a total of approximately 300 nucleotides. These experiments were consistent with the inferences from the theoretical computations. PMID- 22671913 TI - Structural Biology: The State of the Art Volumes One and Two. PMID- 22671915 TI - Comparison of outcomes after typical and atypical eclampsia: a retrospective study. AB - OBJECTIVE: To evaluate the characteristics, clinical features and maternal perinatal outcomes after atypical eclampsia. METHODS: In a retrospective study, we compared demographics, clinical characteristics and outcomes between typical and atypical eclampsia. RESULTS: Of 90 eclamptic patients, 56 had typical eclamptic features and 34 had atypical features. Compared to typical eclampsia, atypical eclampsia had higher gestational age (37.6 +/- 3.3 vs. 34.6 +/- 4.2 weeks, p = 0.001), a higher incidence of no antenatal risk factors [25 (73.5%) vs. 12 (21.4%), p < 0.001], less antepartum seizures [11 (32.4%) vs. 45 (80.4%), p < 0.001], a lower incidence of prodromal symptoms [20 (58.5%) vs. 49 (87.5%), p = 0.002], and a higher incidence of no lesion in brain imaging [16 (47.1%) vs. 12 (21.4%), p = 0.010). Although atypical eclampsia was associated with a lower odd ratio (OR) in composite perinatal complications (OR = 0.22, 95% CI = 0.08-0.60, p = 0.003), composite maternal complications did not differ between the two groups (OR = 0.52, 95% CI = 0.08-0.60, p =0.191). CONCLUSIONS: Maternal outcomes did not differ between the two groups. Therefore, more attention should be focused on atypical eclampsia. PMID- 22671916 TI - Immunodetection of hemocytes, peneidins and alpha2-macroglobulin in the lymphoid organ of white spot syndrome virus infected shrimp. AB - Viral diseases restrict the development of the world shrimp industry and there are few studies on cell response to the presence of viral infections. We performed immunohistochemistry assays to characterize hemocytes subpopulations involved in the immune process occurring in the LO of Litopenaeus vannamei shrimp. Tissue sections of animals that increased their LO spheroids and hemocytes infiltration after WSSV induced infection, were used. Three MABs namely, 40E10 (recognizing small granule hemocytes), 40E2 (recognizing large granule hemocytes), and 41B12, which recognize alpha(2)-macroglobulin were used. Additionally one polyclonal antibody was used against the penaeidins antimicrobial peptides, and to detect WSSV a commercial immunohistochemistry kit (DiagXotics) was used. Numerous small granule hemocytes were detected in the stromal matrix of LO tubules, whereas large granule hemocytes were less numerous and located mainly in hemal sinuses. The exocytosis of two molecules, which have been related to the phagocytosis process, i.e. penaeidins, and alpha(2) macroglobulin, was detected in the external stromal matrix and the outer tubule walls. alpha(2) -macroglobulin inhibits phenoloxidase activity and its strong release in LO tissue may explain the absence of melanization in the immune processes occurring in it. The immunolabeling of vesicles within the LO spheroids with MABs 41B12 40E10 and antipenaedin antibody suggests that LOS are formed by phagocytic cells derived from small granule and hyaline hemocytes, with a possible role of peneidins and alpha(2)-macroglobulin acting as opsonines. PMID- 22671918 TI - Fish immune responses against endoparasitic nematodes - experimental models. AB - Vertebrates mount a series of immune reactions when invaded by helminths but antihelmintic immune strategies allow, in many cases, the first invaders of the non-immune host to survive for prolonged periods, whereas subsequent larval invaders of the same parasite species face increased host resistance and thereby decreased colonization success. This concomitant immunity may represent a trade off between adverse side effects (associated with killing of large helminths in the host tissue) and the need for future protection against invasion. Encapsulation and isolation of large live endoparasitic larvae may be associated with less pathology compared to coping with excess dead parasite tissue in host organs. Likewise, live adult nematodes may be accepted in tissues at a certain activity level for the same reasons. Various host cell receptors bind helminth molecules after which signal-transducing events lead to mobilization of specific reaction patterns depending on the combination of receptors and ligands involved. Both innate and adaptive responses (humoral and cellular) are prominent actors, but skewing of the Th1 lymphocyte response towards a Th2 type is a characteristic element of antihelminthic responses in mammalian hosts. Similar patterns may be expected also to occur in at least some fish species, such as salmonids, producing relevant cytokines, MHCII and CD4+ cells required for these lymphocyte subpopulations. Atlantic cod, Gadus morhua L., is without these immunological elements that indicate that alternative reaction pathways exist in at least some fish groups. Recent achievements within teleost immunology have made it possible to track these host responses in fish and the present work outlines the main immune reactions in fish against helminths and suggests three experimental fish models for exploration of these immune pathways in fish infected with nematodes. PMID- 22671920 TI - A comparison of dental restoration outcomes after placement by restorative function auxiliaries versus dentists. AB - OBJECTIVES: To compare the outcomes of restorations placed by restorative function auxiliaries (RFAs) with those placed by dentists. METHODS: Between July 1, 2007, and June 30, 2008, we matched 455 restorations placed by RFAs working at HealthPartners Dental Group with the same number placed by dentists. Restorations were matched by tooth number, American Dental Association procedure code, and patient age-group. RESULTS: Of 910 restorations, 17 (1.9 percent) had problems potentially related to the filling or crown placement during the first year. Problem rates were not significantly different (p = 0.33) for restorations placed by RFAs (1.3 percent, 6 of 455) and those placed by dentists (2.4 percent, 11 of 455). CONCLUSIONS: There was no significant difference in problem rates for restorations placed by RFAs versus those placed by dentists. This finding may free dentists to handle more difficult cases, alleviating some of the pressures of daily practice and meeting the need for improved access. PMID- 22671919 TI - Cortisol secretory parameters in young exercisers in relation to LH secretion and bone parameters. AB - OBJECTIVE: Amenorrhoea and low bone density are common in excessive exercisers, yet endocrine factors that differentiate adolescent amenorrhoeic exercisers (AE) from eumenorrhoeic exercisers (EE) are unclear. We have previously reported that high ghrelin and low leptin predict lower LH secretion in AE. Leptin and ghrelin impact cortisol secretion, and hypercortisolaemia can inhibit LH pulsatility. We hypothesized that higher cortisol secretion in young endurance weight-bearing AE compared with EE and nonexercisers predicts lower LH secretion, lower levels of a bone formation marker and higher levels of a bone resorption marker. DESIGN: Cross-sectional. SUBJECTS: We studied 21 AE, 18 EE and 20 nonexercisers aged 14 21 years (BMI 10th-90th%iles). MEASUREMENTS: Subjects underwent frequent sampling (11 p.m. to 7 a.m.) to assess cortisol, ghrelin, leptin and LH secretory dynamics. Fasting levels of a bone formation (P1NP) and bone resorption (CTX) marker were measured. RESULTS: BMI did not differ among groups. Cortisol pulse amplitude, mass, half-life and area under the curve (AUC) were highest in AE (P = 0.04, 0.007, 0.04 and 0.003) and were associated inversely with fat mass (r = 0.29, -0.28 and -0.35, P = 0.03, 0.04 and 0.007). We observed inverse associations between cortisol and LH AUC (r = -0.36, P = 0.008), which persisted after controlling for fat mass, leptin and ghrelin AUC. Cortisol correlated positively with CTX in EE and inversely with P1NP in nonexercisers. CONCLUSIONS: Higher cortisol secretion in AE compared with EE and nonexercisers is associated with lower LH secretion. Effects of leptin and ghrelin on LH secretion may be mediated by increased cortisol. PMID- 22671921 TI - Extensive computational study on coordination of transition metal cations and water molecules to glutamic acid. AB - On the basis of the conformations of glutamic acid (Glu) and analysis of possible metal cation coordination and hydration modes, conformations of Glu metalated with transition metal cations (TMCs), Cu(+/2+), Zn(+/2+), and Fe(+/2+/3+) and hydrations of Glu-Cu(+/2+) and Glu-Zn(+/2+) complexes by up to three water molecules are determined by extensive computational searches. The BHandHLYP functional is chosen as the main computational method as its overall performance for treating the spin multiplicity of TMCs is similar to that of CCSD(T) and better than that of MP2 and B3LYP. All mono- and divalent TMCs prefer tridentate coordination to canonical Glu, while Fe(3+) favors a bidentate coordination to zwitterionic Glu. The ground state of Glu-Fe(+) is found to be a spin sextet. Metal ion affinities of Glu for the TMCs are determined, and an excellent agreement with the experiment for Cu(+) may be obtained if the entropic effect is properly accounted for. Effects of hydration on the stabilities of different Glu Cu(+/2+)/Zn(+/2+) structures are discussed, and the hydration energies for up to three water molecules are obtained. For the global minimum to take the zwitterionic form, Glu-Zn(+) requires only monohydration, Glu-Zn(2+) needs to be trihydrated, while Glu-Cu(+/2) should be hydrated with four or more water molecules. PMID- 22671922 TI - The biophysics and biomechanics of cryoballoon ablation. AB - Recent clinical and preclinical studies have demonstrated that cryothermal ablation using a balloon catheter (Artic Front(r), Medtronic CryoCath LP, Pointe Claire, Canada) provides an effective means of achieving pulmonary vein isolation. This review explores the biophysics and biomechanics of cryoballoon ablation. Components of the cryoballoon catheter system are examined, mechanisms of cryothermal injury are summarized, and potential advantages of cryoballoon technology over standard radiofrequency ablation in isolating pulmonary veins are discussed. Practical aspects of biophysics and biomechanics relevant to the clinical electrophysiologist are emphasized, particularly with regards to the selection of the most appropriate cryoballoon catheter and minimizing peri procedural complications. PMID- 22671923 TI - Jasmonic acid transient accumulation is needed for abscisic acid increase in citrus roots under drought stress conditions. AB - Phytohormones are central players in sensing and signaling numerous environmental conditions like drought stress. In this work, an experimental system based on severe drought was established and hormone profiling together with gene expression of key enzymes involved in abscisic acid (ABA) and jasmonic acid (JA) biosynthesis was studied in roots of citrumelo CPB 4475 (a commercial citrus rootstock) plants. JA concentration transiently increased after a few hours of stress, returning to control levels 30 h after the onset of the condition. A more progressive ABA accumulation was observed, with the onset of this increase at the same time or right after the JA transient accumulation. Molecular data suggested that, at least, part of the hormonal regulation takes place at the biosynthetic level. These observations also pointed to a possible involvement of JA on ABA biosynthesis under stress. To test this hypothesis, JA and ABA biosynthesis were chemically inhibited and subsequently phenotypes rescued by the addition of exogenous hormones. Results showed that the early JA accumulation was necessary for the subsequent ABA increase in roots under stress whereas the opposite could not be stated. The model includes a burst of JA in roots of citrus under severe drought stress conditions that leads to a more progressive ABA accumulation that will induce later plant responses. The present work adds a new level of interaction between JA and ABA at the biosynthetic level that together with the previously described interaction between signal transduction cascades of the two hormones would allow plants to fine-tune specific responses to different stimuli. PMID- 22671924 TI - Targeting of adhesion molecules as a therapeutic strategy in multiple myeloma. AB - Multiple myeloma (MM) is a clonal disorder of plasma cells that remains, for the most part, incurable despite the advent of several novel therapeutic agents. Tumor cells in this disease are cradled within the bone marrow (BM) microenvironment by an array of adhesive interactions between the BM cellular residents, the surrounding extracellular matrix (ECM) components such as fibronectin (FN), laminin, vascular cell adhesion molecule-1 (VCAM-1), proteoglycans, collagens and hyaluronan, and a variety of adhesion molecules on the surface of MM cells including integrins, hyaluronan receptors (CD44 and RHAMM) and heparan sulfate proteoglycans. Several signaling responses are activated by these interactions, affecting the survival, proliferation and migration of MM cells. An important consequence of these direct adhesive interactions between the BM/ECM and MM cells is the development of drug resistance. This phenomenon is termed "cell adhesion-mediated drug resistance" (CAM-DR) and it is thought to be one of the major mechanisms by which MM cells escape the cytotoxic effects of therapeutic agents. This review will focus on the adhesion molecules involved in the cross-talk between MM cells and components of the BM microenvironment. The complex signaling networks downstream of these adhesive molecules mediated by direct ligand binding or inside-out soluble factors signaling will also be reviewed. Finally, novel therapeutic strategies targeting these molecules will be discussed. Identification of the mediators of MM-BM interaction is essential to understand MM biology and to elucidate novel therapeutic targets for this disease. PMID- 22671925 TI - Molecular targets for the treatment of multiple myeloma. AB - Multiple myeloma (MM) represents a suitable disease to be treated with Molecularly targeted drugs (MTDs). MM clone aberrations affect signal transduction pathways controlling both proliferation and/or cell survival. Research findings on small drugs or monoclonal antibodies (mAb) against the components of these pathways are now available and related clinical trials in MM patients are rapidly growing up. Promising results have been recently obtained with AKT inhibitors (perifosine) and mTOR inhibitors (everolimus and temsirolimus). However, the activity of these agents used alone is still limited and can be strongly increased by their combination with other drugs such as bortezomib or dexamethasone. The present review will summarize the main signaling components that can be targeted by MTDs and the most important available results derived from the clinical trials based on their use. Another important issue in the treatment of MM is the control of the related bone disease. Two main strategies can be used: i) inhibition of bone resorption and ii) promotion of bone formation. Emerging clinical data suggest that specific MTDs are able to prolong survival not only for the prevention of the skeletal-related events but also for a direct or indirect effect on the proliferation and/or survival of MM cells. A summary on the main preclinical and clinical results in this setting will be provided. In conclusion, the use of MTD in the treatment of MM is a promising approach but still far from becoming a current indication: a new dawn is arising with still unpredictable results. PMID- 22671926 TI - Promises and challenges of MicroRNA-based treatment of multiple myeloma. AB - MicroRNAs (miRNAs) recently emerged with a key role in multiple myeloma (MM) pathophysiology and are considered important regulators of MM cell growth and survival. Since miRNAs can act either as oncogenes or tumour suppressors, the potential of targeting the miRNA network arises as a novel therapeutic approach for human cancer. Potential strategies based on miRNA therapeutics basically rely on miRNA inhibition or miRNA replacement approaches and take benefit respectively from the use of antagomirs or synthetic miRNAs as well as from lipid-based nanoparticles which allow an efficient miRNA-delivery. The availability of experimental in vivo platforms which recapitulate the growth of MM cells within the specific human bone marrow microenvironment in immunocompromised mice (SCID hu and SCID-synth-hu) provides powerful systems for development of miRNA-based therapeutics in MM. Preliminary findings on the anti-MM activity of synthetic miRNAs in such experimental models offer a proof-of-principle that miRNA therapeutics is a promising opportunity for this still incurable disease representing the rationale for a new venue of investigation in this specific field. PMID- 22671928 TI - Novel targets and derived small molecule inhibitors in multiple myeloma. AB - Recent research advances have defined a key role of the bone marrow (BM) in multiple myeloma (MM) pathogenesis thereby leading to new treatment paradigms, which aim to target both the tumor cell as well as its BM microenvironment. The incorporation of thalidomide, bortezomib, and lenalidomide into conventional cytotoxic and transplantation regimens in relapsed and refractory, but also in newly diagnosed MM has changed treatment options during the last decade. However, MM remains still incurable. Ongoing translational research aims to identify additional therapeutic targets and to design derived agents, predominantly small molecule inhibitors, with higher potency and less toxicity to further improve MM patient outcome and to overcome drug resistance. PMID- 22671927 TI - Mouse models as a translational platform for the development of new therapeutic agents in multiple myeloma. AB - Mouse models of multiple myeloma (MM) are basic tools for translational research and play a fundamental role in the development of new therapeutics against plasma cell malignancies. All available models, including transplantable murine tumors in syngenic mice, xenografts of established human cell lines in immunocompromised mice and transgenic models that mirror specific steps of MM pathogenesis, have demonstrated some weaknesses in predicting clinical results, particularly for new drugs targeting the human bone marrow microenvironment (huBMM). The recent interest to models recapitulating the in vivo growth of primary MM cells in a human (SCID-hu) or humanized (SCID-synth-hu) host recipient has provided powerful platforms for the investigation of new compounds targeting MM and/or its huBMM. Here, we review and discuss strengths and weaknesses of the key in vivo models that are currently utilized in the MM preclinical investigation. PMID- 22671929 TI - Targeted therapy of multiple myeloma: the changing paradigm at the beginning of the new millennium. AB - Multiple myeloma (MM) is a malignant hematological neoplasmand constitutes 10% of blood cancers. Recently, it has become evident that almost all cases of MM are preceded by gammopathy of undetermined significance (MGUS). MM is diagnosed by the presence of paraprotein in serum or urine, detected by serum electrophoresis and immunofixation, infiltration of malignant plasma cells in the bone marrow and related organ, or tissue damage. Cytogenetic status, International Staging System (ISS) and the quality of response to therapy are the most important prognostic factors. In the last decade the availability of new effective drugs, such as thalidomide, lenalidomide and bortezomib have provided a new therapeutic scenario expected to impact favorably on the outcome of MM patients. Today, for younger patients a triple-agent induction regimen incorporating novel agents followed by autologous stem cell transplantation (ASCT) is the best approach. In this setting ongoing clinical trials are evaluating the efficacy of consolidation and maintenance therapy based on the use of new drugs. For patients noteligible for ASCT the best initial regimens are combination therapy with melphalan and prednisone plus either thalidomide or bortezomibor the combination of lenalidomide and dexamethasone. Supportive therapy includes the use of erythropoietin and bisphosphonates according to the updated guidelines. In the future the identification of candidate therapeutic targets through gene expression profiling (GEP) and single-nucleotide polymorphism (SNP) analysis, as well as the availability of the targeted investigative agents will lead to a substantial progress in the development and implementation of personalized medicine in MM. PMID- 22671930 TI - MicroRNAs in the pathobiology of multiple myeloma. AB - MicroRNAs (miRNAs) are small non-coding RNAs that bind to the 3'untranslated region of target mRNAs and lead to translation repression or mRNA degradation, thus regulating important cell processes. MiRNA deregulation has been identified in virtually all types of cancer, and miRNA profiling has proved useful in cancer diagnosis, prognosis and response to therapy. So far, limited but important evidence of miRNA impaired expression has been reported in multiple myeloma (MM), suggesting implications in the pathogenesis and biology of the disease. In this review, we present a general overview of the role of miRNAs in B-cell development and associated malignancies, focusing on those most extensively characterized. We fully describe seminal studies on miRNA expression in MM, highlighting the correlations of their deregulation with pathogenesis and with distinct molecular subgroups, as well as their role in prognostic stratification. The data obtained in MM, supported by the consolidated role of miRNAs in cancer and their potential effectiveness in therapy, all provide a solid rationale for the more accurate characterization of their deregulation and the development of effective means of selectively delivering miRNAs and anti-miRNAs to myeloma cells in therapeutic approaches. PMID- 22671931 TI - Modulation of gastrointestinal function by MuDelta, a mixed u opioid receptor agonist/ u opioid receptor antagonist. AB - BACKGROUND & PURPOSE: Loperamide is a selective u opioid receptor agonist acting locally in the gastrointestinal (GI) tract as an effective anti-diarrhoeal but can cause constipation. We tested whether modulating u opioid receptor agonism with delta opioid receptor antagonism, by combining reference compounds or using a novel compound ('MuDelta'), could normalize GI motility without constipation. EXPERIMENTAL APPROACH: MuDelta was characterized in vitro as a potent u opioid receptor agonist and high-affinity delta opioid receptor antagonist. Reference compounds, MuDelta and loperamide were assessed in the following ex vivo and in vivo experiments: guinea pig intestinal smooth muscle contractility, mouse intestinal epithelial ion transport and upper GI tract transit, entire GI transit or faecal output in novel environment stressed mice, or four weeks after intracolonic mustard oil (post-inflammatory). Colonic delta opioid receptor immunoreactivity was quantified. KEY RESULTS: delta Opioid receptor antagonism opposed u opioid receptor agonist inhibition of intestinal contractility and motility. MuDelta reduced intestinal contractility and inhibited neurogenically mediated secretion. Very low plasma levels of MuDelta were detected after oral administration. Stress up-regulated delta opioid receptor expression in colonic epithelial cells. In stressed mice, MuDelta normalized GI transit and faecal output to control levels over a wide dose range, whereas loperamide had a narrow dose range. MuDelta and loperamide reduced upper GI transit in the post inflammatory model. CONCLUSIONS AND IMPLICATIONS: MuDelta normalizes, but does not prevent, perturbed GI transit over a wide dose-range in mice. These data support the subsequent assessment of MuDelta in a clinical phase II trial in patients with diarrhoea-predominant irritable bowel syndrome. PMID- 22671932 TI - Accidental natalizumab administration in pregnancy in multiple sclerosis. PMID- 22671933 TI - Accidental natalizumab administration to the third trimester of pregnancy in an adolescent patient with multiple sclerosis. PMID- 22671934 TI - The effects and experiences of goal setting in stroke rehabilitation - a systematic review. AB - OBJECTIVE: To systematically integrate and appraise the evidence for effects and experiences of goal setting in stroke rehabilitation. DESIGN: Systematic review of quantitative and qualitative studies. METHODS: Relevant databases were searched from start of database to 30 April 2011. Studies of any design employing goal setting, reporting stroke-specific data and evaluating its effects and/ or experiences were included. RESULTS: From a total of 53998 hits, 112 full texts were analysed and 17 studies were included, of which seven evaluated effects while ten explored experiences of goal setting. No eligible randomized controlled trials were identified. Most of the included studies had weak to moderate methodological strengths. The design, methods of goal setting and outcome measures differed, making pooling of results difficult. Goal setting appeared to improve recovery, performance and goal achievement, and positively influenced patients' perceptions of self-care ability and engagement in rehabilitation. However, the actual extent of patient involvement in the goal setting process was not made clear. Patients were often unclear about their role in this process. Professionals reported higher levels of collaboration during goal setting than patients. Patients and professionals differed on how they set goals, types of goals set, and on how they perceived goal attainment. Barriers to goal setting outnumbered the facilitators. CONCLUSION: Due to the heterogeneity and quality of included studies, no firm conclusions could be made on the effectiveness, feasibility and acceptability of goal setting in stroke rehabilitation. Further rigorous research is required to strengthen the evidence base. Better collaboration and communication between patients and professionals and relevant education are recommended for best practice. PMID- 22671935 TI - Crestal remodelling and osseointegration at surface-modified commercially pure titanium and titanium alloy implants in a canine model. AB - BACKGROUND: Ti-6Al-7Nb alloys exhibit enhanced mechanical properties and corrosion resistance and may represent an improvement to present commercially pure (CP) titanium oral implant technology. OBJECTIVES: To evaluate crestal remodelling and osseointegration at CP titanium compared with Ti-6Al-7Nb alloy oral implants using a canine model. METHODS: Two threaded anodized CP titanium and two Ti-6Al-7Nb alloy anodized oral implants (o4.5 * 6.1 mm) were placed into each jaw quadrant in the edentulated posterior mandible in six adult male Hound Labrador mongrel dogs. Abutments were placed onto the implants, and the mucogingival flaps were adapted and sutured for transmucosal wound healing. Block biopsies were collected for histometric analysis following an 8-week healing interval. RESULTS: Healing was uneventful. Bone density outside and within the root of the threads averaged (+/- SE) 49.0 +/- 4.5% and 38.7 +/- 5.1% for CP titanium implants and 43.2 +/- 3.6% and 34.2 +/- 4.8% for Ti-6Al-7Nb alloy implants. Mean osseointegration reached 68.0 +/- 4.4% and 62.8 +/- 2.5% for CP titanium and Ti-6Al-7Nb alloy implants, respectively. Although crestal resorption at lingual sites averaged 0.2 +/- 0.1 mm for both technologies, crestal resorption at buccal sites averaged 0.9 +/- 0.2 and 1.0 +/- 0.6 mm for CP titanium and Ti-6Al-7Nb alloy implants, respectively. There were no statistically significant differences between implant technologies for any parameter assessed. Notably, advanced/advancing buccal crestal resorption exposing the implant threads was observed in 50% of the implants (four of six animals) regardless of implant technology; osteoclastic resorption still observed at 8 weeks following implant placement. CONCLUSION: Within the limitations of study, anodized Ti-6Al 7Nb alloy implants may represent a feasible alternative to benchmark anodized CP titanium implants. Remodelling of the buccal crestal plate resulting in advanced bone loss appears a major impediment to oral implant osseointegration and possibly, in extension, implant maintenance. PMID- 22671936 TI - Enhanced Wnt/beta-catenin signalling during tooth morphogenesis impedes cell differentiation and leads to alterations in the structure and mineralisation of the adult tooth. AB - BACKGROUND INFORMATION: Previous studies have indicated that over-activation of the wingless interaction site (Wnt)/beta-catenin signalling pathway has important implications for tooth development, at the level of cell differentiation and morphology, as well as for the production of supernumerary teeth. Here, we provide evidence for a crucial role of this signalling pathway during the stage of tooth morphogenesis. We have developed an in vitro model consisting of 14.5 day-old mouse embryo first molars, in which the Wnt pathway is overactivated by the glycogen synthase kinase-3 inhibitor 6-bromoindirubin-3'-oxime (BIO; 20 uM). RESULTS: We found that over-activation of the Wnt/beta-catenin pathway delayed the differentiation and growth of the inner dental epithelium. In addition, in contrast to controls in which Nestin protein expression was restricted to differentiated odontoblasts, in BIO-treated molars, Nestin expression spread through sub-odontoblastic cellular layers. This alteration appears to be related to: (i) the over-expression of Bmp4 in the same region, (ii) the delay in odontoblast precursor cell differentiation and (iii) increased proliferation of mesenchymal cells. Furthermore, treatments longer than 6 days induced the malformation of typical dental structures and led to a total lack of cell differentiation. Finally, over-activation of the Wnt route during odontogenesis resulted in adult teeth which presented altered size, morphology and mineralisation. CONCLUSIONS: Our results indicate that Wnt/beta-catenin over activation during tooth morphogenesis is sufficient to cause dramatic alterations in the adult tooth, by delaying cellular differentiation and stimulating proliferation of the dental mesenchyme of developing teeth. PMID- 22671937 TI - The role of real time three-dimensional transesophageal echocardiography in assessing Libman-Sacks endocarditis. AB - A 33-year-old woman was referred to our echocardiography laboratory because of loud murmur at the apex. Transthoracic and transesophageal echocardiography (TTE and TEE) showed a mass involving the anterior leaflet of the mitral valve. Real time three-dimensional TEE (RT3D TEE) images clearly showed the nodular, irregular and large size of the mass. Based on her laboratory findings and the echocardiographic appearance of the mass, Libman-Sacks endocarditis was prediagnosed. In intraoperative inspection, a large nodular tumor was shown on the atrial side of the anterior mitral valve leaflet. In this case, RT3D TEE is better than all echocardiographic imaging modalities in evaulating vegetation of Libman-Sacks endocarditis. PMID- 22671938 TI - Brooding deficits in memory: focusing attention improves subsequent recall. AB - Ruminative habits of thought about one's problems and the resulting consequences are correlated with symptoms of depression and cognitive biases (Nolen-Hoeksema, Wisco, & Lyubomirsky, 2008). In our orienting task, brooders and non-brooders concentrated on self-focusing phrases while they were also exposed to neutral target words. On each trial in the unfocused condition, participants saw and then reported the target before concentrating on the phrase; in the focused condition, the target was reported after phrase concentration. A brooding-related deficit on a subsequent unexpected test of free and forced recall was obtained in the unfocused condition only. Brooders recalled more successfully in the focused than in the unfocused condition. Thus, impaired recall of material unrelated to self concerns may be corrected in situations that constrain attention. PMID- 22671939 TI - Characterizing the surface quality and droplet interface shape for microarray plates. AB - The variation in the surface quality of microarray plates was examined by measuring the contact angles of 480 droplets on five microarray plates. It was found that the measured contact angle did not accurately predict the droplet shape for moderate Bond numbers (~0.5 <= N(B) <= 5). By defining an apparent contact angle using the ratio of the contact radius to the height, the variance in the predicted interface shape decreased by greater than a factor of 3 for both local and globally averaged characteristics. The error in the predicted droplet height was also reduced by 3 orders of magnitude. PMID- 22671940 TI - Complex Forster energy transfer interactions between semiconductor quantum dots and a redox-active osmium assembly. AB - The ability of luminescent semiconductor quantum dots (QDs) to engage in diverse energy transfer processes with organic dyes, light-harvesting proteins, metal complexes, and redox-active labels continues to stimulate interest in developing them for biosensing and light-harvesting applications. Within biosensing configurations, changes in the rate of energy transfer between the QD and the proximal donor, or acceptor, based upon some external (biological) event form the principle basis for signal transduction. However, designing QD sensors to function optimally is predicated on a full understanding of all relevant energy transfer mechanisms. In this report, we examine energy transfer between a range of CdSe-ZnS core-shell QDs and a redox-active osmium(II) polypyridyl complex. To facilitate this, the Os complex was synthesized as a reactive isothiocyanate and used to label a hexahistidine-terminated peptide. The Os-labeled peptide was ratiometrically self-assembled to the QDs via metal affinity coordination, bringing the Os complex into close proximity of the nanocrystal surface. QDs displaying different emission maxima were assembled with increasing ratios of Os peptide complex and subjected to detailed steady-state, ultrafast transient absorption, and luminescence lifetime decay analyses. Although the possibility exists for charge transfer quenching interactions, we find that the QD donors engage in relatively efficient Forster resonance energy transfer with the Os complex acceptor despite relatively low overall spectral overlap. These results are in contrast to other similar QD donor-redox-active acceptor systems with similar separation distances, but displaying far higher spectral overlap, where charge transfer processes were reported to be the dominant QD quenching mechanism. PMID- 22671941 TI - Antioxidant, antihyperglycemic, and antihyperlipidemic effects of Coriandrum sativum leaf and stem in alloxan-induced diabetic rats. AB - In India's indigenous system of medicine, Coriandrum sativum (CS), commonly used as a food ingredient, is claimed to be useful for various ailments. To establish its utility in diabetes mellitus, the present study evaluated the antidiabetic and antioxidant effects of CS in alloxan-induced diabetic rats. The extracts were shown to contain bioactive compounds including phenolics, flavonoids, steroids, and tannins. The extracts of CS in alloxan-induced diabetic rats were found to significantly lower blood glucose levels. Antidiabetic activity of the CS extracts was compared with the clinically available drug glibenclamide. The levels of serum total cholesterol, triglycerides, and low-density lipoprotein cholesterol were lower in the extract-treated group and high-density lipoprotein cholesterol was higher than the diabetic control rats. The extracts of CS exhibited strong scavenging effect on 2, 2-diphenyl-2-picrylhydrazyl free radical and inhibition of lipid peroxidation. The free radical scavenging effect of the extracts was comparable with that of the reference antioxidants. Furthermore, it also showed an improved antioxidant potential as evidenced by decreased lipid peroxidation and a significant increase in the activity of various antioxidant enzymes such as catalase, superoxide dismutase, and glutathione peroxidase in the liver of diabetic rats. These results indicate that the extracts could protect liver function and exhibited hypoglycemic, hypolipidemic, and antioxidant efficacies in the diabetic rats. These results support the use of this plant extract to manage diabetes mellitus. PRACTICAL APPLICATIONS: The leaves and stem of this plant Coriandrum sativum if used in cuisine would be a remedy for diabetes. PMID- 22671942 TI - Oral immunization with attenuated Salmonella vaccine expressing Escherichia coli O157:H7 intimin gamma triggers both systemic and mucosal humoral immunity in mice. AB - Human infections with EHEC such as O157:H7 have been a great concern for worldwide food-industry surveillance. This pathogen is commonly associated with bloody diarrhea that can evolve to the life-threatening hemolytic uremic syndrome. Animals are the natural reservoir where this pathogen remains asymptomatically, in steps of ingestion and colonization of the bowel. The bacterium is shed in the feces, contaminating the surroundings, including water and food that are directed for human consumption. A major player in this colonization process is intimin, an outer membrane adhesion molecule encoded by the E. coli attachment and effacement (eae) gene that has been shown to be essential for intimate bacterial attachment to eukaryotic host cells. In an attempt to reduce the colonization of animal reservoirs with EHEC O157:H7, we designed a vaccine model to induce an immune response against intimin gamma. The model is based on its recombinant expression in attenuated Salmonella, used as a suitable vaccine vector because of its recognized ability to deliver recombinant antigens and to elicit all forms of immunity: mucosal, systemic, and humoral responses. To test this model, mice were orally immunized with a S. enterica serovar Typhimurium strain carrying the pYA3137eaeA vector, and challenged with E. coli O157:H7. Here we show that immunization induced the production of high levels of specific IgG and IgA antibodies and promoted reduction in the fecal shedding of EHEC after challenge. The live recombinant vaccine reported herein may contribute to the efforts of reducing animal intestinal mucosa colonization. PMID- 22671943 TI - Reciprocal relationship between reactive oxygen species and cyclooxygenase-2 and vascular dysfunction in hypertension. AB - AIMS: This study evaluates a possible relationship between reactive oxygen species (ROS) and cyclooxygenase (COX)-2-derived products in conductance and resistance arteries from hypertensive animals. Angiotensin II (Ang II)-infused mice or spontaneously hypertensive rats treated with the NAD(P)H Oxidase inhibitor apocynin, the mitochondrion-targeted SOD2 mimetic Mito-TEMPO, the superoxide dismutase analog tempol, or the COX-2 inhibitor Celecoxib were used. RESULTS: Apocynin, Mito-TEMPO, and Celecoxib treatments prevented Ang II-induced hypertension, the increased vasoconstrictor responses to phenylephrine, and the reduced acetylcholine relaxation. The NOX-2 inhibitor gp91ds-tat, the NOX-1 inhibitor ML171, catalase, and the COX-2 inhibitor NS398 abolished the ex vivo effect of Ang II-enhancing phenylephrine responses. Antioxidant treatments diminished the increased vascular COX-2 expression, prostanoid production, and/or participation of COX-derived contractile prostanoids and thromboxane A(2) receptor (TP) in phenylephrine responses, observed in arteries from hypertensive models. The treatment with the COX-2 inhibitor normalized the increased ROS production (O(2).(-) and H(2)O(2)), NAD(P)H Oxidase expression (NOX-1, NOX-4, and p22phox) and activity, MnSOD expression, and the participation of ROS in vascular responses in both hypertensive models. Apocynin and Mito-TEMPO also normalized these parameters of oxidative stress. Apocynin, Mito-TEMPO, and Celecoxib improved the diminished nitric oxide (NO) production and the modulation by NO of phenylephrine responses in the Ang II model. INNOVATION: This study provides mechanistic evidence of circuitous relationship between COX-2 products and ROS in hypertension. CONCLUSION: The excess of ROS from NAD(P)H Oxidase and/or mitochondria and the increased vascular COX-2/TP receptor axis act in concert to induce vascular dysfunction and hypertension. PMID- 22671944 TI - Understanding causal pathways: response to "teen pregnancy and the achievement gap among urban minority youth". PMID- 22671946 TI - Geographic variations in elementary school-based physical activity practices. AB - BACKGROUND: Physical activity (PA) is associated with health and academic benefits among children, but many schools do not meet national recommendations. This study examined school-based PA practices in nationally representative samples of public elementary schools, and geographic variations in those practices. METHODS: Mail-back surveys were used to gather data from 578 public elementary schools during the 2006-2007 school year and 680 public elementary schools during the 2009-2010 school year. RESULTS: Nationwide, only 1 in 5 schools met the national recommendation of at least 150 minutes of physical education (PE) per week, although PE was more prevalent in the South. Nearly three-fourths of schools nationwide met recommendations for 20 or more minutes of recess daily, and this was more prevalent in the Midwest but less so in the South. Approximately 40% of schools offered sports and approximately 40% offered other opportunities for PA during the school day. The only practice that increased over time was formal classroom instruction on PA. CONCLUSIONS: There has been little change in elementary school-based PA practices nationwide in recent years. With the upcoming renewal of the Elementary and Secondary Education Act, policymakers have an important opportunity to promote increased PA in schools. PMID- 22671947 TI - Examining school-based pedometer step counts among children in grades 3 to 6 using different timetables. AB - BACKGROUND: Advocates for the implementation of the Balanced School Day (BSD) schedule argue that this schedule will increase opportunities for physical activity. However, the relationship between this scheduling change and its impact on physical activity has not been examined. Thus, this study assessed levels of physical activity in students attending 2 different schools: 1 using the BSD and the other using the Traditional School Day (TSD) schedule. METHODS: Participation of students between grades 3 and 6 was sought. Data were collected over 4 school days using pedometers. Independent Sample t tests and 1-way analysis of variance (ANOVA) were performed. RESUTLS: A total of 117 students participated. Overall, average daily step counts for boys (6972 +/- 1952) were significantly higher than girls (5742 +/- 1495; p < .001). These average step counts represent 47% and 48% of the recommended amount of steps needed for health benefits for children between the ages of 6 and 12. The average daily step count for students using the BSD schedule was 6017 (+/-1666), while the average daily step count for students using the TSD schedule was 6788 (+/-1987). The difference in steps (771) was statistically significant (p = .03). CONCLUSIONS: These results do not support claims that the BSD offers increased physical activity. In fact, these results suggest that students enrolled in schools using the BSD schedule may have reduced daily physical activity. In addition, these results demonstrate that overall school-based physical activity is less than half of the recommended level; independent of school scheduling. PMID- 22671948 TI - Analysis of influential factors associated with the smoking behavior of aboriginal schoolchildren in remote Taiwanese mountainous areas. AB - BACKGROUND: A disparity in smoking behavior exists between the general and minority populations residing in Taiwan's mountainous areas. This study analyzed individual and environmental factors associated with children's smoking behavior in these areas of Taiwan. METHODS: In this school-based study, data on smoking behavior and related factors for mountain-dwelling students were obtained from the 2008 and 2009 Control of School-aged Children Smoking Study surveys. A representative sample (N = 1239) from 26 primary schools was included. The association among 3 groups (never-, former-, and current-smokers) and the potential variables were simultaneously examined using unordered polytomous logistic regression analysis. RESULTS: Between 13% and 34% of ever-smokers reported that their first smoking experience was in third grade. More than 70% were found to have bought cigarettes and 87% reported that the tobacco retailers had sold them cigarettes. The significant factors for current-smokers were predisposing factors, ie, attitude toward smoking (adjusted odds ratio [AOR] = 1.21); reinforcing factors, ie, family smoked in front of me (AOR = 2.44), friends smoked in front of me (AOR = 16.24), and school staff smoked in front of me (AOR = 2.98); and enabling factors, ie, cigarette availability and accessibility (AOR = 2.16 and 2.42, respectively). A student's perceived punishment for smoking at school had a positive significant effect on the risk of being former-smokers (AOR = 1.57). CONCLUSION: The findings provide a basis for school and community to design and implement effective anti-smoking programs for remote mountain-based students to further reduce youth smoking. PMID- 22671949 TI - Integrating life skills into a theory-based drug-use prevention program: effectiveness among junior high students in Taiwan. AB - BACKGROUND: Drug use has been noted among students in Taiwan during the past decade and schools have a role in preventing or delaying students' drug use. We developed and evaluated a school-based, drug-use prevention program integrating the theory of planned behavior (TPB) and life skills for junior high school students. METHODS: We recruited 441 seventh graders from randomly selected schools: N = 143 experimental groups, N = 142 conventional groups, and N = 156 control groups. The experimental group received ten 45-minute sessions of theory based interventions. The conventional group got traditional didactic teaching and drug refusal skills. The control group received no intervention. RESULTS: Compared to the control group, experimental group students showed greater improvement in attitude, subjective norm, perceived behavioral control, life skills, and intention not to use drugs. Compared to the conventional group, the experimental group had significantly higher posttest scores for 4 of the 5 outcomes, including life skills (96.53 vs. 90.92, p < .001), attitude (27.43 vs. 24.40, p = .012), subjective norm (29.51 vs. 28.06, p = .002), and perceived behavioral control (18.59 vs. 16.81, p < .001). The conventional group scored significantly higher in behavioral intention than did the control group. CONCLUSION: Study results demonstrated the effectiveness of a drug-use prevention program integrating the TPB and life skills. PMID- 22671950 TI - Work-related violence, lifestyle, and health among special education teachers working in Finnish basic education. AB - BACKGROUND: Studies have reported higher levels of absenteeism due to illness among special education teachers compared to other teachers, but it is not known which factors might contribute to this difference. We examined whether health, health behaviors, and exposure to violence at work differed between special education and general education teachers in Finnish basic education. METHODS: Survey data from 5760 general and special education teachers were analyzed with multilevel logistic models adjusted for individual- and school-level confounding factors. RESULTS: No difference was found between the health behaviors of general and special education teachers. The differences in physical and mental health between the two groups were also relatively small. With regard to work-related violence, however, male special education teachers were 3 times more likely to be exposed to mental abuse, and 5 times more likely to be exposed to physical violence when compared to their male colleagues in general education. Although female special educators were also at an increased risk of mental abuse and physical violence compared to their female general teacher colleagues, their odds ratios for such an encounter were smaller (2- and 3-fold, respectively) than those of male special education teachers. The school-level variance of physical violence toward teachers was large, which indicates that while most schools have little physical violence toward teachers, schools do exist in which teachers' exposure to violence is common. CONCLUSIONS: These findings suggest that special education teachers may benefit from training for handling violent situations and interventions to prevent violence at schools. PMID- 22671951 TI - Monohafnium oxide clusters HfO(n)- and HfO(n) (n = 1-6): oxygen radicals, superoxides, peroxides, diradicals, and triradicals. AB - The electronic and structural properties of monohafnium oxide clusters, HfO(n)(-) and HfO(n) (n = 1-6), are investigated using anion photoelectron spectroscopy and density-functional theory at the B3LYP level. The observed ground-state adiabatic detachment energy is low for HfO(-) (0.5 +/- 0.1 eV) and HfO(2)(-) (2.125 +/- 0.010 eV), roughly constant for HfO(3)(-) (3.6 +/- 0.1 eV), HfO(4)(-) (3.67 +/- 0.05 eV), and HfO(5)(-) (3.9 +/- 0.1 eV), and substantially higher for HfO(6)(-) (4.9 +/- 0.1 eV). Activated oxygen species, such as radical, superoxide, peroxide, diradical, and triradical, are identified in the HfO(n)(-) and HfO(n) clusters. The Hf center is shown to be flexible to accommodate the oxygen species. The sum of formal Hf-O bond orders around the Hf center is equal to four for all of the neutral clusters studied, and five for all of the anions. The O rich HfO(n)(-) and HfO(n) (n = 3-6) clusters provide well-defined molecular models to understand O(2) adsorption and activation on an Hf center. PMID- 22671956 TI - Ninth Conversation in the Discipline Biomolecular Stereodynamics The University, Albany, New York, June 20-24, 1995. PMID- 22671952 TI - CD4+ and CD8+ regulatory T cells (Tregs) are elevated and display an active phenotype in patients with chronic HCV mono-infection and HIV/HCV co-infection. AB - The aim of this study was to examine regulatory T cells (Tregs) in peripheral blood and liver tissue in patients with chronic hepatitis C virus (HCV) mono infection and in patients with HIV/HCV co-infection. In a cross-sectional study were included 51 patients with chronic HCV infection, 24 patients with HIV/HCV co infection and 24 healthy individuals. CD4+ and CD8+ Tregs were determined using flow cytometry. Fibrosis was examined by transient elastography. Inflammation, fibrosis and Tregs were determined in liver biopsies from 12 patients. Increased frequency of CD4+ and CD8+ Tregs was found in HIV/HCV co-infected patients [median: 6.4% (IQR: 5.7-6.9) and 1.0% (0.7-1.2), respectively] compared to HCV mono-infected patients [5.6% (4.2-6.3), P = 0.01 and 0.5% (0.3-0.7), P < 0.001, respectively]. Furthermore, HCV mono-infected patients had increased frequencies of Tregs compared with healthy controls (P < 0.05). However, no associations between the frequency of Tregs and fibrosis were found. Furthermore, characterization of CD4+ Tregs using CD45RA demonstrated a higher frequency of activated Tregs in both HCV mono-infected and HIV/HCV co-infected patients compared with healthy controls. Finally, number of intrahepatic Tregs was associated with both peripheral CD8+ Tregs and intrahepatic inflammation. In conclusion, HCV mono-infected patients and particularly HIV/HCV co-infected patients have increased the frequency of CD4+ and CD8+ Tregs compared with healthy controls. Furthermore, CD4+ Tregs in infected patients displayed an active phenotype. Tregs were not associated with fibrosis, but a positive correlation between intrahepatic Tregs and inflammation was found. Taken together, these results suggest a role for Tregs in the pathogenesis of chronic HCV infection. PMID- 22671957 TI - Age-related changes of skin blood flow during postocclusive reactive hyperemia in human. AB - BACKGROUND/PURPOSE: The objective was to study age-related alterations in the time-amplitude characteristics of the oscillatory components of peripheral blood flow in healthy humans during postocclusive reactive hyperemia. METHODS: Forearm blood skin perfusion was studied by the method of laser Doppler flowmetry in 120 healthy volunteers, who were divided into two age groups: young (19-30 years old; n = 82) and middle-age (30-60 years old; n = 38). The forearm occlusion approach was used to reveal the reaction of the microvascular bed to transient ischemia. To estimate the age-related changes of separate oscillatory components of LDF signals during postocclusive reactive hyperemia, we applied adaptive time amplitude wavelet analysis. RESULTS: A statistically significant increase in the skin blood perfusion after occlusion removal was revealed: 4-fold in the 1st and 3.5-fold in the 2nd group respectively. Both the amplitude of blood flow oscillations at rest and the postocclusive growth of the amplitude showed an age related decline in the frequency intervals associated with the myogenic (0.052 0.145 Hz), sympathetic (0.021-0.052 Hz) and endothelial (0.0095-0.021 Hz) activity. CONCLUSION: The time-amplitude characteristics of the oscillatory components of peripheral blood flow depend on age, with the dependence becoming more evident after a transient ischemia. PMID- 22671958 TI - Intelligent modelling of oesophageal cancer treatment and its use to determine the dose of chemotherapy drug. AB - In this paper, the behaviour of oesophageal cancer has been modelled to provide treatment for patients with oesophageal squamous carcinoma. In this method, the dose of chemotherapy drugs is calculated using a combination of neural networks. Implementation shows that the proposed method is able to effectively treat oesophageal cancer. The results of the proposed method for determining chemotherapy drug dose are in most cases consistent with expert medical opinion. PMID- 22671959 TI - Functions of DNA methyltransferase 3-like in germ cells and beyond. AB - DNA methyltransferase 3-like (DNMT3L) is one of the key players in de novo DNA methylation of imprinting control elements and retrotransposons, which occurs after genome-wide epigenetic erasure during germ cell development. In this review, we summarise the biochemical properties of DNMT3L and discuss the possible mechanisms behind DNMT3L-mediated imprinting establishment and retrotransposon silencing in germ cells. We also discuss possible connections between DNMT3L and non-coding RNA-mediated epigenetic remodelling, the roles of DNMT3L in germ cell development and the implications in stem cell and cancer research. PMID- 22671961 TI - Interactive effects of UV radiation and water availability on seedlings of six woody Mediterranean species. AB - To assess the effects of UV radiation and its interaction with water availability on Mediterranean plants, we performed an experiment with seedlings of six Mediterranean species (three mesophytes vs three xerophytes) grown in a glasshouse from May to October under three UV conditions (without UV, with UVA and with UVA+UVB) and two irrigation levels (watered to saturation and low watered). Morphological, physiological and biochemical measures were taken. Exposure to UVA+UVB increased the overall leaf mass per area (LMA) and the leaf carotenoids/chlorophyll a + b ratio of plants in relation to plants grown without UV or with UVA, respectively. In contrast, we did not find a general effect of UV on the leaf content of phenols or UVB-absorbing compounds of the studied species. Regarding plant growth, UV inhibited the above-ground biomass production of well watered plants of Pistacia lentiscus. Conversely, under low irrigation, UVA tended to abolish the reduction in growth experienced by P. lentiscus plants growing in a UV-free environment, in accordance with UVA-enhanced apparent electron transport rate (ETR) values under drought in this species. UVA also induced an overall increase in root biomass when plants of the studied species were grown under a low water supply. In conclusion, while plant exposition to UVA favored root growth under water shortage, UVB addition only gave rise to photoprotective responses, such as the increase in LMA or in the leaf carotenoids/chlorophyll a + b ratio of plants. Species-specific responses to UV were not related with the xerophytic or mesophytic character of the studied species. PMID- 22671962 TI - What is the gold standard for intrapartum fetal monitoring? AB - The health authorities of Stockholm county recently published a Health Technology Assessment report: "Fetal monitoring with computerized STAN analysis during labor - a systematic review" with the aim to ensure that high quality research information on costs, effectiveness and broader impact of health technologies is analysed and presented in the most efficient way for those who use, manage and work in this field. The report claims to analyse available research in relation to ST interval analysis of fetal electrocardiogram (STAN) and concludes that scientific evidence for advantages of the STAN technology for maternal and fetal outcome was insufficient and that clinical use cannot be recommended and should be restricted to research protocols. The Norwegian reference group for fetal surveillance points out that the report suffers from two insufficiencies: selection bias by not providing a complete collection of the evidence for the clinical performance of the STAN technology and, secondly, that it does not provide evidence-based alternative methods. PMID- 22671963 TI - C-reactive protein as a prognostic marker for advanced renal cell carcinoma treated with sunitinib. AB - OBJECTIVES: To investigate the prognostic role of C-reactive protein in patients with advanced renal cell carcinoma treated with sunitinib. METHODS: A total of 41 consecutive patients with advanced clear-cell renal cell carcinoma treated with sunitinib between December 2008 and August 2011 were included in this study. Logistic regression analysis estimated the relative importance of non-tumor variables, including C-reactive protein, and selected adverse events as predictive factors for sunitinib responses. RESULTS: Overall, 11 patients (26.8%) showed a partial response and 10 patients (24.4%) had stable disease. On univariate analysis, Memorial Sloan-Kettering Cancer Center non-poor risk, normal C-reactive protein, hand-foot skin reaction, altered taste, fatigue and leukopenia were significantly correlated with objective responses (P = 0.020, 0.001, 0.006, 0.006, 0.023 and 0.037, respectively). On multivariate analysis, normal C-reactive protein was independently associated with objective response (P = 0.016). Patients with a normal level of C-reactive protein (<=0.30 mg/dL) had a significantly higher partial response plus stable disease rate (84.6% vs 35.7%, P = 0.002) and significantly longer progression-free survival (median 19.0 vs 6.0 months, P = 0.036) than patients with an elevated level of C-reactive protein. CONCLUSIONS: C-reactive protein is an independent prognostic indicator for patients with advanced renal cell carcinoma treated with sunitinib. PMID- 22671965 TI - Electrophysiology testing and the National Cardiovascular Data Registry: stimulating, yet inconclusive. AB - In this issue of PACE, Cheng et al. do an impressive job in evaluating clinical variables associated with electrophysiology studies (EPS) performed within 1 month before implantable cardioverter defibrillator (ICD) placement in 33,786 individuals entered into the National Cardiovascular Data Registry for Implantable Cardioverter Defibrillators (NCDR(r)-ICD) over a 3-year period. Although of great interest, most of the conclusions are by necessity based on conjecture drawn from observations alone, since the inherent, point-in-time structure of the Registry limits the ability to assess accurate longitudinal clinical correlations and outcomes. The fact is, we really do not know why these patients underwent EPS or how the data from these tests were used. In addition to stimulating speculation on the role of EPS in ICD recipients, the present report should promote caution regarding what conclusions can and should be drawn from the NCDR(r)-ICD in its present format. As constructed, the Registry provides demographic data and clinical elements up to only a fixed point in time. Hence, the ability to draw conclusions is limited by the abundance of disconnected variables and snapshot quality of data in the NCDR. PMID- 22671966 TI - Computerised working memory training in healthy adults: a comparison of two different training schedules. AB - This study compared a high intensity working memory training (45 minutes, 4 times per week for 4 weeks) with a distributed training (45 minutes, 2 times per week for 8 weeks) in middle-aged, healthy adults. The aim was to clarify whether a computerised working memory training is effective and whether intensity of training influences training outcome. To evaluate the efficacy and possible transfer effects, a neuropsychological test battery assessing short- and long term memory, working memory, executive functions and mental speed was applied at baseline and at retest. Our results indicate that the distributed training led to increased performance in all cognitive domains when compared to the high intensity training and the control group without training. The most significant differences revealed by interaction contrasts were found for verbal and visual working memory, verbal short-term memory and mental speed. These results support the hypothesis that cognitive enhancement by cognitive intervention is effective in healthy individuals, and that a distributed training schedule is superior to a high intensity intervention. PMID- 22671967 TI - Surface chemistry, reactivity, and pore structure of porous silicon oxidized by various methods. AB - Oxidation is the most commonly used method of passivating porous silicon (PSi) surfaces against unwanted reactions with guest molecules and temporal changes during storage or use. In the present study, several oxidation methods were compared in order to find optimal methods able to generate inert surfaces free of reactive hydrides but would cause minimal changes in the pore structure of PSi. The studied methods included thermal oxidations, liquid-phase oxidations, annealings, and their combinations. The surface-oxidized samples were studied by Fourier transform infrared spectroscopy, isothermal titration microcalorimetry, nitrogen sorption, ellipsometry, X-ray diffraction, electron paramagnetic resonance spectroscopy, and scanning electron microscopy imaging. Treatment at high temperature was found to have two advantages. First, it enables the generation of surfaces free of hydrides, which is not possible at low temperatures in a liquid or a gas phase. Second, it allows the silicon framework to partially accommodate a volume expansion because of oxidation, whereas at low temperature the volume expansion significantly consumes the free pore volume. The most promising methods were further optimized to minimize the negative effects on the pore structure. Simple thermal oxidation at 700 degrees C was found to be an effective oxidation method although it causes a large decrease in the pore volume. A novel combination of thermal oxidation, annealing, and liquid-phase oxidation was also effective and caused a smaller decrease in the pore volume with no significant change in the pore diameter but was more complicated to perform. Both methods produced surfaces that were not found to react with a model drug cinnarizine in isothermal titration microcalorimetry experiments. The study enables a reasonable choice of oxidation method for PSi applications. PMID- 22671968 TI - Hydrotris(triazolyl)borate complexes as functional models for Cu nitrite reductase: the electronic influence of distal nitrogens. AB - Hydrotris(triazolyl)borate (Ttz) ligands form CuNO(x) (x = 2, 3) complexes for structural and functional models of copper nitrite reductase. These complexes have distinct properties relative to complexes of hydrotris(pyrazolyl)borate (Tp) and neutral tridentate N-donor ligands. The electron paramagnetic resonance spectra of five-coordinate copper complexes show rare nitrogen superhyperfine couplings with the Ttz ligand, indicating strong sigma donation. The copper(I) nitrite complex [PPN](+)[(Ttz(tBu,Me))Cu(I)NO(2)](-) has been synthesized and characterized and allows for the stoichiometric reduction of NO(2)(-) to NO with H(+) addition. Anionic Cu(I) nitrite complexes are unusual and are stabilized here for the first time because Ttz is a good pi acceptor. PMID- 22671969 TI - Association between obesity and periodontal disease in young adults: a population based birth cohort. AB - AIM: To evaluate the association between obesity and periodontal disease and the mediating effect of oral hygiene, systemic inflammation and carbohydrate intake. MATERIAL AND METHODS: Subjects born in 1982 in Pelotas, Brazil (n = 5,914), have been followed for several times. Oral health was assessed in a representative sample of 720 individuals at 24 years. Obesity, waist circumference and number of episodes with obesity between 15 and 23 years of age were the main exposures. Mediating effect of oral hygiene, C-reactive protein level and carbohydrate consumption was also assessed. RESULTS: Obese individuals were more likely to have >= 2 teeth with gingival bleeding. However, after adjusting for confounders, the association was not statistically significant [OR (obese * 2 or more teeth) 1.72 (95% CI: 0.95, 3.11)] and adjustment for potential mediators decreased the OR (OR = 1.38). The risk of presenting calculus in obese subjects was 10% higher [PR 1.10 (95% CI: 1.02, 1.18)]. The number of episodes of obesity between 15 and 23 years was associated with dental calculus. Periodontal pockets were not associated with obesity. CONCLUSION: Systemic inflammation and oral hygiene may be mediating the association between obesity and gingivitis. Obesity was not associated with periodontal pockets in young adults in this cohort. PMID- 22671970 TI - Separability of tight and roaming pathways to molecular decomposition. AB - Recent studies have questioned the separability of the tight and roaming mechanisms to molecular decomposition. We explore this issue for a variety of reactions including MgH(2) -> Mg + H(2), NCN -> CNN, H(2)CO -> H(2) + CO, CH(3)CHO -> CH(4) + CO, and HNNOH -> N(2) + H(2)O. Our analysis focuses on the role of second-order saddle points in defining global dividing surfaces that encompass both tight and roaming first-order saddle points. The second-order saddle points define an energetic criterion for separability of the two mechanisms. Furthermore, plots of the differential contribution to the reactive flux along paths connecting the first- and second-order saddle points provide a dynamic criterion for separability. The minimum in the differential reactive flux in the neighborhood of the second-order saddle point plays the role of a mechanism divider, with the presence of a strong minimum indicating that the roaming and tight mechanisms are dynamically distinct. We show that the mechanism divider is often, but not always, associated with a second-order saddle point. For the formaldehyde and acetaldehyde reactions, we find that the minimum energy geometry on a conical intersection is associated with the mechanism divider for the tight and roaming processes. For HNNOH, we again find that the roaming and tight processes are dynamically separable but we find no intrinsic feature of the potential energy surface associated with the mechanism divider. Overall, our calculations suggest that roaming and tight mechanisms are generally separable over broad ranges of energy covering most kinetically relevant regimes. PMID- 22671971 TI - Efficacy and safety of 'true' cinnamon (Cinnamomum zeylanicum) as a pharmaceutical agent in diabetes: a systematic review and meta-analysis. AB - AIMS: Diabetes is a leading cause of morbidity and mortality worldwide. Studies have frequently looked at dietary components beneficial in treatment and prevention. We aim to systematically evaluate the literature on the safety and efficacy of Cinnamomum zeylanicum on diabetes. METHODS: A comprehensive search of the literature was conducted in the following databases; PubMed, Web of Science, Biological Abstracts, SciVerse Scopus, SciVerse ScienceDierect, CINAHL and The Cochrane Library. A meta-analysis of studies examining the effect of C. zeylanicum extracts on clinical and biochemical parameters was conducted. Data were analysed using RevMan v5.1.2. RESULTS: The literature search identified 16 studies on C. zeylanicum (five in-vitro, six in-vivo and five in-vivo/in-vitro). However, there were no human studies. In-vitro C. zeylanicum demonstrated a potential for reducing post-prandial intestinal glucose absorption by inhibiting pancreatic alpha-amylase and alpha-glucosidase, stimulating cellular glucose uptake by membrane translocation of glucose transporter-4, stimulating glucose metabolism and glycogen synthesis, inhibiting gluconeogenesis and stimulating insulin release and potentiating insulin receptor activity. The beneficial effects of C. zeylanicum in animals include attenuation of diabetes associated weight loss, reduction of fasting blood glucose, LDL and HbA(1c) , increasing HDL cholesterol and increasing circulating insulin levels. Cinnamomum zeylanicum also significantly improved metabolic derangements associated with insulin resistance. It also showed beneficial effects against diabetic neuropathy and nephropathy, with no significant toxic effects on liver and kidney and a significantly high therapeutic window. CONCLUSION: Cinnamomum zeylanicum demonstrates numerous beneficial effects both in vitro and in vivo as a potential therapeutic agent for diabetes. However, further randomized clinical trials are required to establish therapeutic safety and efficacy. PMID- 22671972 TI - Redox proteomics. AB - Proteins are major targets of reactive oxygen and nitrogen species (ROS/RNS) and numerous post-translational, reversible or irreversible modifications have been characterized, which may lead to a change in the structure and/or function of the oxidized protein. Redox proteomics is an increasingly emerging branch of proteomics aimed at identifying and quantifying redox-based changes within the proteome both in redox signaling and under oxidative stress conditions. Correlation between protein oxidation and human disease is widely accepted, although elucidating cause and effect remains a challenge. Increasing biomedical data have provided compelling evidences for the involvement of perturbations in redox homeostasis in a large number of pathophysiological conditions and aging. Research toward a better understanding of the molecular mechanisms of a disease together with identification of specific targets of oxidative damage is urgently required. This is the power and potential of redox proteomics. In the last few years, combined proteomics, mass spectrometry (MS), and affinity chemistry-based methodologies have contributed in a significant way to provide a better understanding of protein oxidative modifications occurring in various biological specimens under different physiological and pathological conditions. Hence, this Forum on Redox Proteomics is timely. Original and review articles are presented on various subjects ranging from redox proteomics studies of oxidatively modified brain proteins in Alzheimer disease and animal models of Alzheimer and Parkinson disease, to potential new biomarker discovery paradigm for human disease, to chronic kidney disease, to protein nitration in aging and age-related neurodegenerative disorders, electrophile-responsive proteomes of special relevance to diseases involving mitochondrial alterations, to cardiovascular physiology and pathology. PMID- 22671973 TI - Novel recombinant BCG coexpressing Ag85B, ESAT-6 and Rv2608 elicits significantly enhanced cellular immune and antibody responses in C57BL/6 mice. AB - Tuberculosis (TB) remains an enormous global health problem, and a new vaccine against TB more potent than the current inadequate vaccine, the Bacille Calmette Guerin (BCG), is urgently needed. BCG has proven to be an effective recombinant delivery vehicle for foreign antigens because of its ability to induce long-lived specific humoral and cellular immunity. Experimental evidences have revealed that Ag85B, ESAT-6 and Rv2608 are important immunodominant antigens of Mycobacterium tuberculosis and are all promising vaccine candidate molecules. In this study, we have constructed a novel recombinant BCG (rBCG) expressing fusion protein Ag85B ESAT6-Rv2608 and evaluated the immunogenicity of rBCG in C57BL/6 mice. Results show there is strong TB-specific CD4+ and CD8+ T lymphocytes proliferative response in mice immunized with rBCG vaccine, especially the cytotoxic CD8+ T cells playing an important role in protection against TB. And rBCG immunization has induced a significantly strong Th1 immune response, characterized by the increased ratio of IgG2b/IgG1. Results also show that rBCG immunization could increase the secretion of Th1 cytokines such as TNF-alpha and IL-2 and could decrease the secretion of Th2 cytokine IL-10. Moreover, it was shown that rBCG immunization induced a strong humoral response in mice, characterized by the elevated IgG titre. Therefore, we conclude that this rBCG immunization could increase both cellular immune response and antigen-specific humoral response significantly as compared to BCG immunization in mice. The above results illustrated that rBCG::Ag85B-ESAT6-Rv2608 is a potential candidate against M. tuberculosis for further study. PMID- 22671974 TI - Comparative antigenic proteins and proteomics of pathogenic Yersinia enterocolitica bio-serotypes 1B/O: 8 and 2/O: 9 cultured at 25 degrees C and 37 degrees C. AB - Yersinia enterocolitica is a Gram-negative enteric pathogen responsible for a number of gastrointestinal disorders; the most pathogenic bio-serotype is 1B/O: 8. In this study, we compared the antigenicity of the outer membrane proteins and proteomics of the whole-cell proteins of a pathogenic bio-serotype 2/O: 9 isolated in China and a bio-serotype 1B/O: 8 strain isolated in Japan. Using two dimensional gel electrophoresis, we showed that the outer membrane proteins A (OmpA), C (OmpC) and F (OmpF) were the major antigens for both strains, although proteins located on the bacterial cell membrane and enzymes involved in energy metabolism were also identified as antigenic. We compared the whole-cell proteins of the two strains cultured at 25 degrees C and 37 degrees C and found portions of the outer membrane proteins (OmpX, OmpF and OmpA) were downregulated when the bacteria were cultured at 37 degrees C, whereas urease subunit gamma (UreA), urease subunit alpha (UreC) and urease accessory protein (UreE), which are involved in urease synthesis, were upregulated when the bacteria were grown at 37 degrees C. These observations will lay a foundation to selection of diagnostic markers for pathogenic Yersinia enterocolitica, and maybe contribute to choose the vaccine targets. PMID- 22671975 TI - Phospholipase C-gamma1 expression correlated with cancer progression of potentially malignant oral lesions. AB - BACKGROUND: Phospholipase C-gamma1 (PLCgamma1) is required for cellular migration during tumor progression and invasion of oral squamous cell carcinoma (OSCC) cells. The objective of the current study was to determine immunoexpression pattern of PLCgamma1 in oral potentially malignant lesions (OPLs) and evaluate PLCgamma1 usefulness as a biomarker for predicting clinical behavior in the carcinogenesis of OPL. METHODS: In a retrospective follow-up study, the expression pattern of PLCgamma1 protein was determined using immunohistochemistry in samples from 68 patients, including untransformed cases (n = 38) and malignant transformed cases (n = 30). The corresponding post-malignant lesions (OSCCs) were also performed. RESULTS: We observed that elevated expression of PLCgamma1 in 40 of 68 (59%) general OPLs and 23 of 30 (77%) OSCCs compared with that in normal oral mucosa. Kaplan-Meier analysis revealed that patients with PLCgamma1 positivity had a significantly higher incidence of OSCC than those with PLCgamma1 negativity. Cox regression analysis revealed that PLCgamma1 expression patterns were significantly associated with increased risk of malignant progression. In addition, the correlation between PLCgamma1 expression in pre-malignant OPL and that in post-malignant OSCC was significant (P = 0.004). CONCLUSION: These data indicate that PLCgamma1 expression in OPL correlated with oral cancer progression, and PLCgamma1 may serve as a useful marker for the identification of high-risk OPL into OSCC. PMID- 22671976 TI - The delicate balance between inflammation, conception and pregnancy. PMID- 22671977 TI - Evolution of variations in the common pattern of stomatogenesis in peritrich ciliates: evidence from a comparative Study including a new description of stomatogenesis in Pseudepistylis songi Peng et al., 2007. AB - The stomatogenesis of peritrich ciliates is an important developmental process but has been studied relatively little for such a large, diverse taxon. Complex oral structures and an inability of staining techniques to reveal them clearly have been the major factors hindering investigation of this process. In the present study, an improved method of staining with protargol was used to investigate the entire process of stomatogenesis in a large, colonial species of peritrich, Pseudepistylis songi, and to compare it to descriptions of stomatogenesis in several other species. We found that P. songi and other peritrichs have the same general type of ophryobuccokinetal stomatogenesis, with the parental oral complex being inherited by one daughter and the new oral complex by the other daughter; however, some differences between individual taxa appear to have arisen in the course of evolution. Reorganization of the entire germinal kinety (Gk) to form the germinal anlage may be plesiomorphic, with restriction of reorganization to its abstomal part being apomorphic. Development of the entire new haplokinety of one daughter cell (2Hk) from the germinal band or its homologue also appears to be plesiomorphic, with development of peristomial and infundibular parts of 2Hk from separate rudiments being apomorphic. Furthermore, development of the new Gk of the parental oral complex (1Gk) from the entire infundibular part of the parental haplokinety (1Hk) may be plesiomorphic, and development from just the abstomal part may be apomorphic. Finally, development of the Gk of the new oral complex (2Gk) from residual kinetosomes of the germinal band appears to be plesiomorphic. PMID- 22671979 TI - A Thermodynamic and Mutational Analysis of an RNA Purine Loop as a Protein Binding Site. PMID- 22671980 TI - Beneficial effects of solar UV-B radiation on soybean yield mediated by reduced insect herbivory under field conditions. AB - Ultraviolet-B radiation (UV-B: 280-315 nm) has damaging effects on cellular components and macromolecules. In plants, natural levels of UV-B can reduce leaf area expansion and growth, which can lead to reduced productivity and yield. UV-B can also have important effects on herbivorous insects. Owing to the successful implementation of the Montreal Protocol, current models predict that clear-sky levels of UV-B radiation will decline during this century in response to ozone recovery. However, because of climate change and changes in land use practices, future trends in UV doses are difficult to predict. In the experiments reported here, we used an exclusion approach to study the effects of solar UV-B radiation on soybean crops, which are extensively grown in many areas of the world that may be affected by future variations in UV-B radiation. In a first experiment, performed under normal management practices (which included chemical pest control), we found that natural levels of UV-B radiation reduced soybean yield. In a second experiment, where no pesticides were applied, we found that solar UV B significantly reduced insect herbivory and, surprisingly, caused a concomitant increase in crop yield. Our data support the idea that UV-B effects on agroecosystems are the result of complex interactions involving multiple trophic levels. A better understanding of the mechanisms that mediate the anti-herbivore effect of UV-B radiation may be used to design crop varieties with improved adaptation to the cropping systems that are likely to prevail in the coming decades in response to agricultural intensification. PMID- 22671981 TI - Rapid and accurate analyses of silicon and phosphorus in plants using a portable X-ray fluorescence spectrometer. AB - The elemental analysis of plant material is a frequently employed tool across biological disciplines, yet accurate, convenient and economical methods for the determination of some important elements are currently lacking. For instance, digestion-based techniques are often hazardous and time-consuming and, particularly in the case of silicon (Si), can suffer from low accuracy due to incomplete solubilization and potential volatilization, whilst other methods may require large, expensive and specialised equipment. Here, we present a rapid, safe and accurate procedure for the simultaneous, nonconsumptive analysis of Si and phosphorus (P) in as little as 0.1 g dried and ground plant material using a portable X-ray fluorescence spectrometer (P-XRF). We used certified reference materials from different plant species to test the analytical performance of P XRF and show that the analysis suffers from very little bias and that the repeatability precision of the measurements is as good as or better than that of other methods. Using this technique we were able to process and analyse 200 ground samples a day, so P-XRF could provide a particularly valuable tool for plant biologists requiring the simultaneous nonconsumptive analysis of multiple elements, including those known to be difficult to measure such as Si, in large numbers of samples. PMID- 22671983 TI - Validation of a handoff assessment tool: the Handoff CEX. AB - AIMS AND OBJECTIVES: Test the feasibility and validity of a handoff evaluation tool for nurses. BACKGROUND: No validated tools exist to assess the quality of handoff communication during change of shift. DESIGN: Prospective cohort study. METHODS: A standardised tool, the Handoff CEX, was developed based on the mini CEX. The tool consisted of seven domains scored on a 1-9 scale. Nurse educators observed shift-to-shift handoff reports among nurses and evaluated both the provider and recipient of the report. Nurses participating in the report simultaneously evaluated each other as part of their handoff. RESULTS: Ninety eight evaluations were obtained from 25 reports. Scores ranged from 3-9 in all domains except communication and setting (4-9). Experienced (>five years) nurses received significantly higher mean scores than inexperienced (<= five years) nurses in all domains except setting and professionalism. Mean overall score for experienced nurses was 7.9 vs 6.9 for inexperienced nurses. External observers gave significantly lower scores than peer evaluators in all domains except setting. Mean overall score by external observers was 7.1 vs. 8.1 by peer evaluators. Participants were very satisfied with the evaluation (mean score 8.1). CONCLUSIONS: A brief, structured handoff evaluation tool was designed that was well-received by participants, was felt to be easy to use without training, provided data about a wide range of communication competencies and discriminated well between experienced and inexperienced clinicians. Relevance to clinical practice. This tool may be useful for educators, supervisors and practicing nurses to provide training, ongoing assessment and feedback to improve the quality of handoff. PMID- 22671984 TI - Evaluation of indigenous bacterial strains for biocontrol of the frogeye leaf spot of soya bean caused by Cercospora sojina. AB - AIMS: Assessment of biological control of Cercospora sojina, causal agent of frogeye leaf spot (FLS) of soya bean, using three indigenous bacterial strains, BNM297 (Pseudomonas fluorescens), BNM340 and BNM122 (Bacillus amyloliquefaciens). METHODS AND RESULTS: From cultures of each bacterial strain, cell suspensions and cell-free supernatants were obtained and assayed to determine their antifungal activity against C. sojina. Both mycelial growth and spore germination in vitro were more strongly inhibited by bacterial cell suspensions than by cell-free supernatants. The Bacillus strains BNM122 and BNM340 inhibited the fungal growth to a similar degree (I ~ 52-53%), while cells from P. fluorescens BNM297 caused a lesser reduction (I ~ 32-34%) in the fungus colony diameter. The foliar application of the two Bacillus strains on soya bean seedlings, under greenhouse conditions, significantly reduced the disease severity with respect to control soya bean seedlings and those sprayed with BNM297. This last bacterial strain was not effective in controlling FLS in vivo. CONCLUSIONS: Our data demonstrate that the application of antagonistic bacteria may be a promising and environmentally friendly alternative to control the FLS of soya bean. SIGNIFICANCE AND IMPACT OF THE STUDY: To our knowledge, this is the first report of biological control of C. sojina by using native Bacillus strains. PMID- 22671986 TI - The influence of surfactants and hydrolyzed proteins on keratinocytes viability and elasticity. AB - BACKGROUND/PURPOSE: The knowledge how surfactants and hydrolyzed proteins influence the elastic properties of living epidermal keratinocytes is sparse. We demonstrate that the stiffness of cells measured by atomic force microscope (AFM) can be correlated with viability test. METHODS AND MATERIALS: The effects of sodium lauryl sulphate (SLS) and hydrolyzed collagen (HK) of molecular weight 9 kDa were examined with respect to human keratinocytes viability and elasticity. MTT assay was applied to determine the survival fraction of keratinocytes treated with SLS and HK solutions of various molar ratios. The AFM measurements of the keratinocytes stiffness were carried out immediately after the exposure of cells to the SLS and HK, respectively. RESULTS: The increase of the SLS concentration resulted in the decrease of cells proliferation and this effect was inhibited by addition of HK. The strongest inhibition was observed for the SLS:HK molar ratio equals to 2:1. AFM study shows decrease in the cell stiffness for cells treated with SLS. Fluorescence microscopy reveals remodeling of actin filaments of SLS treated cells. SLS:HK mixture treatment results in mechanical stiffness close to untreated cells. CONCLUSION: These results provide possible correlations between mechanical properties and viability of keratinocytes when the chemical stress occurs. PMID- 22671987 TI - Bioactive sesquiterpenoids from the rhizomes of Acorus calamus. AB - Eight new sesquiterpenes (1-8) and one new norsesquiterpene (9) named calamusins A-I were isolated from the ethanol extract of Acorus calamus rhizomes. The absolute configuration of compound 8 was determined by comparing its experimental and calculated ECD spectra. The absolute configurations of the other compounds were determined from their CD spectra. Furthermore, in in vitro assays, compounds 3, 4, 7, and 9 (10 MUM) exhibited weak hepatoprotective activities against APAP induced HepG2 cell damage. PMID- 22671988 TI - Measurement of social climate within neurobehavioural rehabilitation services using the EssenCES. AB - In forensic mental health settings, quality of social climates is associated with a range of therapeutic assets. An essential characteristic of neurobehavioural rehabilitation services is provision of an enriched environment which reverses contingencies that maintain challenging behaviour. The concept of social climate is therefore equally important to these services. Criticisms of existing measures of social climate led to development of the EssenCES. This was initially validated in German forensic mental hospitals, and subsequently an English translation in equivalent UK services. To determine if EssenCES can be used to measure social climate in neurobehavioural rehabilitation units, responses from 114 staff and patients were analysed using statistical methods from classical test theory. Results were similar to those obtained previously. Rasch analysis was also used to test the assumption that EssenCES comprises a true interval scale measurement tool. Item-person misfit, erratic responding, redundant response categories and disordered thresholds undermined this assumption. Rating scale recalibration, item reduction, and removing respondents who continued to demonstrate poor fit resulted in a measure with good internal construct validity but questionable external construct validity. Relative merits of modifying EssenCES for use with patients with cognitive impairment versus designing a measure conceptualised for use in neurobehavioural rehabilitation services are discussed. PMID- 22671985 TI - Induction and exacerbation of psoriasis with Interferon-alpha therapy for hepatitis C: a review and analysis of 36 cases. AB - BACKGROUND: Interferon-alpha (IFN-alpha) therapy is used to treat hepatitis C infection. The exacerbation and occurrence of psoriasis in hepatitis C patients treated with IFN-alpha is increasingly recognized, but the distinct associated features, aetiology and management have not been reviewed. OBJECTIVE: To review all published cases of hepatitis C patients who developed psoriasis while receiving IFN-alpha therapy. METHODS: The review was conducted by searching the PubMed database using the keywords 'hepatitis C' AND 'psoriasis.' In addition, references to additional publications not indexed for PubMed were followed to obtain a complete record of published data. RESULTS: We identified 32 publications describing 36 subjects who developed a psoriatic eruption while receiving IFN-alpha therapy for hepatitis C. Topical therapies were a commonly employed treatment modality, but led to resolution in only 30% of cases in which they were employed solely. Cessation of IFN-alpha therapy led to resolution in 93% of cases. Hundred per cent of those who developed psoriasis while on IFN alpha therapy responded to systemic therapy and were able to continue the drug. CONCLUSION: Further studies and analysis of IFN-alpha-induced lesions are necessary to clarify the role of IFN-alpha and the hepatitis C virus in the development of psoriatic lesions. PMID- 22671989 TI - Syntheses, structures, optical and magnetic properties of Ba2MLnSe5 (M = Ga, In; Ln = Y, Nd, Sm, Gd, Dy, Er). AB - The twelve quaternary rare-earth selenides Ba(2)MLnSe5 (M = Ga, In; Ln = Y, Nd, Sm, Gd, Dy, Er) have been synthesized for the first time. The compounds Ba(2)GaLnSe(5) (Ln = Y, Nd, Sm, Gd, Dy, Er) are isostructural and crystallize in a new structure type in the centrosymmetric space group P 1 of the triclinic system while the isostructural compounds Ba(2)InLnSe(5) (Ln = Y, Nd, Sm, Gd, Dy, Er) belong to the Ba(2)BiInS(5) structure type and crystallize in the noncentrosymmetric space group Cmc2(1) of the orthorhombic system. The structures contain infinite one-dimensional anionic chains (1)(infinity)[GaLnSe(5)](4-) and (1)(infinity)[InLnSe(5)](4-), and both chains are built from LnSe(6) octahedra and MSe(4) (M = Ga, In) tetrahedra in the corresponding selenides. As deduced from the diffuse reflectance spectra, the band gaps of most Ba(2)MLnSe(5) (M = Ga, In; Ln = Y, Nd, Sm, Gd, Dy, Er) compounds are around 2.2 eV. The magnetic susceptibility measurements on Ba(2)GaGdSe(5) and Ba(2)InLnSe(5) (Ln = Nd, Gd, Dy, Er) indicate that they are paramagnetic and obey the Curie-Weiss law, while the magnetic susceptibility of Ba(2)InSmSe(5) deviates from the Curie-Weiss law as a result of the crystal field splitting. Furthermore, Ba(2)InYSe(5) exhibits a strong second harmonic generation response close to that of AgGaSe(2), when probed with the 2090 nm laser as fundamental wavelength. PMID- 22671990 TI - The association of histologic placental inflammation with category II fetal heart tracings. AB - The present study assessed whether placentas in women delivered by cesarean for category II fetal heart tracings (FHT) exhibit a higher incidence of acute inflammation than those of women delivered by cesarean for labor arrest. This case control study included singleton pregnancies >=36 weeks of gestation delivered by cesarean for an FHT indication (cases) or because of labor arrest (controls) 2005-2009 at Prentice Women's Hospital. Exclusions were maternal diabetes, hypertension, known thrombophilia, connective tissue disorders, clinical evidence of chorioamnionitis, placental abruption, fetal anomalies, stillbirth, or an infant with a birth weight less than the 10th percentile. Women were included in the case group if the indication for cesarean delivery was based on the FHT and review of the FHT determined that they were designated as category II prior to delivery. A perinatal pathologist, unaware of indications for delivery, assessed placental inflammation in maternal and fetal compartments. Stage and grade of acute inflammation, from none to severe (scored 0-3), in the membranes, chorionic plate, chorionic vessels, and umbilical cord were assessed, and overall maternal and fetal inflammatory stages were assigned. Findings indicative of chronic inflammation were also noted. Other than lower umbilical artery cord gases in women with category II FHT, cases (n = 51) and controls (n = 27) had similar baseline characteristics and newborn outcomes, as well as similar placental pathologic findings. In uncomplicated patients, the presence or extent of placental inflammation does not appear to differ between women delivered for category II FHT and labor arrest. PMID- 22671991 TI - Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio are prolonged in patients with moderate and severe obstructive sleep apnea. AB - BACKGROUND: Prolongation of the peak and the end of T wave (Tp-e) has been reported to be associated with ventricular arrhythmias. Tp-e/QT ratio and Tp e/QTc ratio are used as an index of ventricular arrhythmogenesis. An increased incidence of ventricular arrhythmias has been reported in patients with obstructive sleep apnea (OSA). The aim of this study was to assess ventricular repolarization in patients with OSA by using Tp-e interval, Tp-e/QT ratio, and Tp e/QTc ratio. METHODS: We have studied 72 patients who underwent overnight polysomnography (PSG) between the years 2010-2011 at our institution. Patients with moderate and severe OSA (23 patients; mean age: 45+/-10), according to the apnea-hypopnea index, constituted the study group. Patients with normal PSG (23 patients; mean age: 42+/-11) were used as the control group. In all patients, Tp e interval, Tp-e/QT ratio, Tp-e/QTc ratio, as well as some other electrocardiogram intervals were measured. Independent samples t-tests were used for comparison of continuous and categorical variables and correlations were calculated by Spearman rank correlation. RESULTS: Although QT and QTc intervals were not different between the groups, mean Tp-e interval (81.6+/-11.1 msn; 63.9+/-7.3 msn; respectively; P < 0.001), Tp-e/QT ratio (0.21+/-0.03; 0.17+/ 0.02; respectively; P < 0.001), and Tp-e/QTc ratio (0.20+/-0.03; 0.16+/-0.02; respectively; P < 0.001) were prolonged in the study group compared to the control group. Correlation analysis showed a significant positive correlation between the presence of moderate and severe OSA and Tp-e interval (r = 0.72; P < 0.001), Tpe/QT ratio (r = 0.70; P < 0.001), and Tp-e/QTc ratio (r = 0.70; P < 0.001). CONCLUSIONS: Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio are prolonged in patients with moderate and severe OSA patients. There is a positive correlation between the presence of OSA and Tp-e interval, Tp-e/QT ratio, and Tp e/QTc ratio. PMID- 22671992 TI - Relationship of advanced oxidative protein products in human saliva and plasma: age- and gender-related changes and stability during storage. AB - The blood levels of advanced oxidative protein products (AOPP) elevate in aging and age-related diseases. However, saliva AOPP in healthy humans have been unexplored. Thus, we investigated 143 Chinese healthy adults to assay age- and gender-related changes in saliva and plasma AOPP levels and the stability of saliva AOPP stored both at - 20 degrees C and - 80 degrees C. We found the mean AOPP levels in saliva and plasma of 119 subjects were 7.51 +/- 3.20 and 28.31 +/- 5.53 MUmol/L (MUM). An age-dependent increase was observed in both saliva and plasma AOPP levels. This increase was particularly significant in the elderly subjects compared with that in the young and middle-aged ones. A significant positive correlation among age, saliva and plasma AOPP levels was observed. No gender-dependent difference was observed in either saliva or plasma AOPP levels during the aging process. Furthermore, AOPP levels in the 24 saliva samples showed no significant change at every successive determination during 4 weeks at 80 degrees C, whereas those levels significantly increased after 7 days of storage at - 20 degrees C. These results indicate the feasibility to screen aging biochemical indicators using saliva AOPP as an alternative to blood AOPP. Saliva AOPP samples are suitable to be stored at - 80 degrees C. PMID- 22671993 TI - Inter- and intramolecular mechanisms for chlorine rearrangements in trimethyl substituted N-chlorohydantoins. AB - The antimicrobial compounds 1-chloro-3,5,5-trimethylhydantoin and 3-chloro-1,5,5 trimethylhydantoin (1 and 2, respectively) have been synthesized and examined via a joint experimental and computational study. The measured rate of loss of oxidative chlorine in the absence and presence of exposure to UVA irradiation determined 2 to be less stable than 1. An interesting migration reaction was observed during UVA irradiation that featured the production of chlorine rearrangement and dechlorinated compounds. Two novel hydrogen atom transfer reaction (HATR) mechanisms have been proposed: (1) an intramolecular process in which a hydrogen atom undergoes a series of sigmatropic shifts, and (2) an intermolecular pathway in which a radical abstracts a hydrogen atom from a neighboring molecule. Density functional theory (DFT) calculations at the UB3LYP/6-311G++(2d,p) theory level have been employed to elucidate the preferred reaction pathway. Both proposed HATR mechanisms predicted 2 to possess a lower free energy of activation, DeltaG(?), relative to 1 in accordance with the experimental stability measurements. However, the intermolecular route had an overall lower absolute DeltaG(?) and was more consistent with measured product ratios in solution. The intermolecular reaction pathway, unlike the intramolecular route, also predicted the lack of formation of a migration product featuring a Cl covalently bonded to a methylene group at the 5-position of the hydantoin moiety, which was verified by NMR experiments. PMID- 22671994 TI - An overnight increase in CO2 predicts mortality in sleep disordered breathing. AB - BACKGROUND AND OBJECTIVE: Sleep disordered breathing (SDB) is highly prevalent but under-recognized. Evidence is accumulating for its role as a predictor of mortality independent of cardiovascular risk factors. The role of hypercapnia in SDB is not known systematically, and between 11 and 43% of patients with SDB develop chronic hypercapnia. Hypercapnia predicts mortality in other respiratory conditions. The role of hypercapnia in independently predicting mortality in patients with SDB after assessing for the presence of airways disease and obesity was investigated. METHODS: The records of 396 consecutive patients were examined retrospectively. Univariate and multivariate analyses were performed using Cox proportional hazards regression to determine the association between gas exchange and polysomnography (PSG) variables and all-cause mortality, adjusted for potential confounders, including age, gender and presence of co-morbidity and airways disease. RESULTS: The mean age of our patient population was 55 +/- 15 years, and the mean body mass index (BMI) was 30.6 +/- 6.2 kg/m2 . Out of the 322 patient population, 258 were men. After 10 years, 25% had died, following a maximum follow-up of 16.7 years. Mortality among patients with SDB was predicted by a difference between evening and morning PaCO2 (DeltaPaCO2 ) of >=7 mm Hg and evening hypoxaemia (PaO2 < 65 mm Hg), independent of age and the presence of co morbidity and airways disease. There was a significant correlation between minimum oxygen saturation (SpO2 ) and DeltaPaCO2 >= 7 mm Hg (P = 0.002) and evening PaO2 < 65 mm Hg (P < 0.001). CONCLUSIONS: An overnight increase in CO2 and evening hypoxaemia are independent mortality predictors in SDB. A low minimum SpO2 identifies patients in whom morning and evening arterial blood gases are beneficial. PMID- 22671995 TI - A comparative study of a preservative-free latanoprost cationic emulsion (Catioprost) and a BAK-preserved latanoprost solution in animal models. AB - PURPOSE: Benzalkonium chloride (BAK), a common preservative in eye drops, can induce ocular surface toxicity that may decrease glaucoma therapy compliance. The ocular hypotensive effect, pharmacokinetic (PK) profiles, and local tolerance of a preservative-free latanoprost 0.005% cationic emulsion (Catioprost((r))), and a BAK-preserved latanoprost 0.005% solution (Xalatan((r))), were compared. METHODS: The ocular hypotensive effect was evaluated in monkeys with elevated intraocular pressure (IOP) induced by laser photocoagulation of the trabecular meshwork. Each monkey (n=8) received both latanoprost formulations once daily for 5 consecutive treatment days in a crossover design with at least a 2-week washout period between treatments. IOP was measured at baseline (on day 1, no instillation), on vehicle treatment day (day 0), and on treatment days 1, 3, and 5 before drug instillation and then hourly for 6 h. In rabbits, the ocular and systemic concentrations of latanoprost free acid were determined following a single instillation and the local tolerance of twice daily instillations over 28 days was assessed. RESULTS: Both the preservative-free and BAK-preserved latanoprost formulations shared the same efficacy profile with the maximum IOP reduction occurring 2 h after each morning dose (-15%, -20%, and -26%; -15%, -23%, and -23% on days 1, 3, and 5, respectively) and lasting through 24 h. The equivalence in efficacy was confirmed by the PK data demonstrating similar area under the curves (AUCs). While both formulations were well tolerated, the incidence of conjunctival hyperemia was reduced by 42% with the BAK-free latanoprost cationic emulsion. CONCLUSIONS: In animal models, a preservative-free latanoprost cationic emulsion was as effective as Xalatan((r)) for lowering IOP with an improved ocular tolerance profile. PMID- 22671996 TI - Evaluation of field-effect mobility and contact resistance of transistors that use solution-processed single-walled carbon nanotubes. AB - Solution-processed single-walled carbon nanotubes (SWNTs) offer many unique processing advantages over nanotubes grown by the chemical vapor deposition (CVD) method, including capabilities of separating the nanotubes by electronic type and depositing them onto various substrates in the form of ultradensely aligned arrays at low temperature. However, long-channel transistors that use solution processed SWNTs generally demonstrate inferior device performance, which poses concerns over the feasibility of using these nanotubes in high-performance logic applications. This paper presents the first systematic study of contact resistance, intrinsic field-effect mobility (MU(FE)), and conductivity (sigma(m)) of solution-processed SWNTs based on both the transmission line method and the Y function method. The results indicate that, compared to CVD nanotubes, although solution-processed SWNTs have much lower MU(FE) for semiconducting nanotubes and lower sigma(m) for metallic nanotubes due to the presence of a higher level of structural defects, such defects do not affect the quality of electric contacts between the nanotube and metal source/drain electrodes. Therefore, solution processed SWNTs are expected to offer performance comparable to that of CVD nanotubes in ultimately scaled field-effect transistors, where contacts will dominate electron transport instead of electron scattering in the channel region. These results show promise for using solution-processed SWNTs for high performance nanoelectronic devices. PMID- 22671997 TI - The p53-Bak apoptotic signaling axis plays an essential role in regulating differentiation of the ocular lens. AB - The tumor suppressor p53 is a master regulator of apoptosis and also plays a key role in cell cycle checking. In our previous studies, we demonstrated that p53 directly regulates Bak in mouse JB6 cells (Qin et al. 2008. Cancer Research. 68(11):4150) and that p53-Bak signaling axis plays an important role in mediating EGCG-induced apoptosis. Here, we demonstrate that the same p53-Bak apoptotic signaling axis executes an essential role in regulating lens cell differentiation. First, during mouse lens development, p53 is expressed and differentially phosphorylated at different residues. Associated with p53 expression, Bak is also significantly expressed during mouse lens development. Second, human p53 directly regulates Bak promoter and Bak expression in p53 knockout mice (p53-/-) was significantly downregulated. Third, during in vitro bFGF-induced lens cell differentiation, knockdown of p53 or Bak leads to significant inhibition of lens cell differentiation. Fourth, besides the major distribution of Bak in cytoplasm, it is also localized in the nucleus in normal lens or bFGF-induced differentiating lens cells. Finally, p53 and Bak are co localized in both cytoplasm and nucleus, and their interaction regulates the stability of p53. Together, these results demonstrate for the first time that the p53-Bak apoptotic signaling axis plays an essential role in regulating lens differentiation. PMID- 22671998 TI - Diagnostic accuracy of heart-rate recovery after exercise in the assessment of diabetic cardiac autonomic neuropathy. AB - AIMS: Poor prognosis associated with blunted post-exercise heart-rate recovery may reflect autonomic dysfunction. This study sought the accuracy of post exercise heart-rate recovery in the diagnosis of cardiac autonomic neuropathy, which represents a serious, but often unrecognized complication of Type 2 diabetes. METHODS: Clinical assessment of cardiac autonomic neuropathy and maximal treadmill exercise testing for heart-rate recovery were performed in 135 patients with Type 2 diabetes and negative exercise echocardiograms. Cardiac autonomic neuropathy was defined by abnormalities in >= 2 of 7 autonomic function markers, including four cardiac reflex tests and three indices of short-term (5 min) heart-rate variability. Heart-rate recovery was defined at 1-, 2- and 3-min post-exercise. RESULTS: Patients with cardiac autonomic neuropathy (n = 27; 20%) had lower heart-rate recovery at 1-, 2- and 3-min post-exercise (P < 0.01). Heart rate recovery demonstrated univariate associations with autonomic function markers (r-values 0.20-0.46, P < 0.05). Area under the receiver-operating characteristic curve revealed good diagnostic performance of all heart-rate recovery parameters (range 0.80-0.83, P < 0.001). Optimal cut-offs for heart-rate recovery at 1-, 2- and 3-min post-exercise were <= 28 beats/min (sensitivity 93%, specificity 69%), <= 50 beats/min (sensitivity 96%, specificity 63%) and <= 52 beats/min (sensitivity 70%, specificity 84%), respectively. These criteria predicted cardiac autonomic neuropathy independently of relevant clinical and exercise test information (adjusted odds ratios 7-28, P < 0.05). CONCLUSIONS: Post-exercise heart-rate recovery provides an accurate diagnostic test for cardiac autonomic neuropathy in Type 2 diabetes. The high sensitivity and modest specificity suggests heart-rate recovery may be useful to screen for patients requiring clinical autonomic evaluation. PMID- 22671999 TI - "X"-shaped incision and keloid skin-flap resurfacing: a new surgical method for auricle keloid excision and reconstruction. PMID- 22672000 TI - Lipopolysaccharide appears to activate human endometrial endothelial cells through TLR-4-dependent and TLR-4-independent mechanisms. AB - PROBLEM: Uterine innate immunity remains poorly characterized, and while endometrial endothelial cells are known to express Toll-like receptors (TLRs), little is known about their function in these cells. The present study evaluated the effect of Gram-negative bacterial lipopolysaccharide (LPS) on human endometrial endothelial cell (HEECs) cytokine secretion and tissue factor expression, and the role of TLR-4 in these responses. METHODS: Human endometrial endothelial cells were treated with or without LPS +/- LPS-RS, a TLR-4 antagonist, via the binding of MD-2. After 24 hr, cell-free supernatants were evaluated for cytokines by multiplex analysis and cell lysates were analyzed for tissue factor expression by Western blot. RESULTS: Treatment of HEECs with LPS significantly upregulated the secretion of IL-6, IL-8, and G-CSF, and this was prevented by LPS-RS. LPS also induced tissue factor expression by the HEECs; however, this was unaffected by LPS-RS. CONCLUSION: These findings suggest that TLR-4 is functional in HEECs and its activation by bacterial LPS induces a specific cytokine/chemokine response. However, bacterial LPS also induced tissue factor expression in what seemed to be a TLR-4-independent fashion, suggesting that this bacterial component can act on the HEECs through TLR-4-dependent and TLR-4-independent pathways. These findings indicate that endometrial endothelial cells may play an active role in uterine innate immunity. PMID- 22672001 TI - Field analysis of photoprotection in co-occurring cool climate C(3) and C(4) grasses. AB - C(4) photosynthesis is particularly successful at high light intensities and high temperatures, but is relatively rare when the average growing season temperature is less than about 15 degrees C. We tested the hypothesis that rapidly reversible photoprotection enables some C(4) species to tolerate cool climates, by focusing on two questions: (1) Do chlorophyll fluorescence responses differ seasonally between co-occurring C(3) and C(4) grasses in the field? (2) Does xanthophyll-mediated photoprotection differ between the two pathways? Spartina pectinata (C(4) ) and Calamogrostis canadensis (C(3) ) were sampled in a herbaceous fresh-water meadow in New Brunswick, Canada (45 degrees N 66 degrees W). Non-photochemical thermal energy dissipation (Phi(NPQ) ) and the epoxidation state of the xanthophyll cycle (EPS) were used as indicators of photoprotection. We observed no differential susceptibility to chronic photoinhibition (i.e. photodamage) between the C(3) and C(4) species, except potentially during spring emergence. On average, C. canadensis showed higher levels of protective dynamic photoinhibition throughout the growing season, but S. pectinata had greater Phi(NPQ) and lower EPS during seasonal and daily temperature minima. The low Rubisco capacity of C(4) species is a potential limiting factor to C(4) success at high latitudes, but our findings suggest that it is unlikely via a photoinhibitory feedback mechanism. PMID- 22672003 TI - Response to Replacing ranibizumab with bevacizumab on the Pharmaceutical Benefits Scheme: where does the current evidence leave us? PMID- 22672002 TI - C-H bond functionalization via hydride transfer: formation of alpha-arylated piperidines and 1,2,3,4-tetrahydroisoquinolines via stereoselective intramolecular amination of benzylic C-H bonds. AB - We here report a study of the intramolecular amination of sp(3) C-H bonds via the hydride transfer cyclization of N-tosylimines (HT-amination). In this transformation, 5-aryl aldehydes are subjected to N-toluenesulfonamide in the presence of BF(3).OEt(2) to effect imine formation and HT-cyclization, leading to 2-arylpiperidines and 3-aryl-1,2,3,4-tetrahydroisoquinolines in a one-pot procedure. We examined the reactivity of a range of aldehyde substrates as a function of their conformational flexibility. Substrates of higher conformational rigidity were more reactive, giving higher yields of the desired products. However, a single substituent on the alkyl chain linking the N-tosylimine and the benzylic sp(3) C-H bonds was sufficient for HT-cyclization to occur. In addition, an examination of various arenes revealed that the electronic character of the hydridic C-H bonds dramatically affects the efficiency of the reaction. We also found that this transformation is highly stereoselective; 2-substituted aldehydes yield cis-2,5-disubstituted piperidines, while 3-substituted aldehydes afford trans-2,4-disubstituted piperidines. The stereoselectivity is a consequence of thermodynamic control. The pseudoallylic strain between the arene and tosyl group on the piperidine ring is proposed to rationalize the greater stability of the isomer with the aryl ring in the axial position. This preferential placement of the arene is proposed to affect the observed stereoselectivity. PMID- 22672005 TI - First CORE China meeting, 20-23 October 2011. PMID- 22672004 TI - IgA anti-epidermal transglutaminase autoantibodies: a sensible and sensitive marker for diagnosis of dermatitis herpetiformis in adult patients. AB - BACKGROUND: Dermatitis herpetiformis (DH) is a rare gluten-sensitive blistering itchy skin disease, strictly related to coeliac disease (CD). Direct immunofluorescence, demonstrating IgA granular deposits localized either in the dermal papillae or along the dermo-epidermal junction, is currently the gold standard for diagnosis of DH. It has been shown that DH immunocomplexes contain epidermal transglutaminase (eTG) and that sera from patients with DH contain antibodies specifically directed against eTG. OBJECTIVES: We studied the usefulness of serum eTG antibodies in discriminating between DH, CD and other gastrointestinal and dermatologic diseases. METHODS: eTG antibodies were tested in 308 adult patients' sera: 44 patients with untreated dermatitis herpetiformis (UDH), 99 patients with untreated coeliac disease (UCD), 70 dermatological controls and 95 gastrointestinal controls. RESULTS: In UDH eTG antibody levels were significantly higher than in DH patients on gluten-free diet, UCD, gastrointestinal controls and dermatological controls. In UCD eTG antibodies strongly correlated with tissue transglutaminase (tTG) antibodies, whereas in UDH no significant correlation was observed. CONCLUSION: Serum IgA eTG antibody determination can efficiently distinguish UDH from other dermatological itchy diseases and is highly sensitive to gluten-free diet. PMID- 22672006 TI - Evolution of elongation factor-like (EFL) protein in Rhizaria is revised by radiolarian EFL gene sequences. AB - Elongation factor 1alpha (EF-1alpha) and elongation factor-like (EFL) proteins are considered to carry out equivalent functions in translation in eukaryotic cells. Elongation factor 1alpha and EFL genes are patchily distributed in the global eukaryotic tree, suggesting that the evolution of these elongation factors cannot be reconciled without multiple lateral gene transfer and/or ancestral co occurrence followed by differential loss of either of the two factors. Our current understanding of the EF-1alpha/EFL evolution in the eukaryotic group Rhizaria, composed of Foraminifera, Radiolaria, Filosa, and Endomyxa, remains insufficient, as no information on EF-1alpha/EFL gene is available for any members of Radiolaria. In this study, EFL genes were experimentally isolated from four polycystine radiolarians (i.e. Dictyocoryne, Eucyrtidium, Collozoum, and Sphaerozoum), as well as retrieved from publicly accessible expressed sequence tag data of two acantharean radiolarians (i.e. Astrolonche and Phyllostaurus) and the endomyxan Gromia. The EFL homologs from radiolarians, foraminiferans, and Gromia formed a robust clade in both maximum-likelihood and Bayesian phylogenetic analyses, suggesting that EFL genes were vertically inherited from their common ancestor. We propose an updated model for EF-1alpha/EFL evolution in Rhizaria by incorporating new EFL data obtained in this study. PMID- 22672008 TI - Terlipressin-induced extensive skin necrosis: a case report and published work review. PMID- 22672009 TI - First flatus time and xerostomia associated with gum-chewing after liver resection. AB - AIMS AND OBJECTIVES: The aim of this study was to compare the return of bowel function and xerostomia in patients who were and were not instructed to chew gum after elective open liver resection. BACKGROUND: Patients who undergo liver resection have limited early ambulation, because they require bed rest after surgery to prevent internal bleeding. They normally also require narcotic analgesics or patient-controlled analgesia for pain control. For these reasons, they often have symptoms of intestinal gas accumulation, abdominal distension and/or abdominal pain. DESIGN: Prospective case-control study. METHODS: Forty-two patients with hepatocellular carcinoma who were treated at Samsung Medical Center from September 2010 to February 2011 were included in this study. Patients who were scheduled for elective liver resection for hepatocellular carcinoma and were over 30 years of age were eligible. Patients were assigned to a gum-chewing group or a non-gum-chewing (control) group before surgery. RESULTS: The mean age of the gum-chewing group was 54.9 (+/-9.7) years, and the mean age of the control group was 55.1 (+/-8.4) years. The mean values of first flatus time and xerostomia were higher in the control group than in the gum-chewing group. First flatus time and xerostomia grade were significantly decreased in gum-chewing group compared with the control group after adjustment for hospitalisation days, duration of surgery and amount of analgesics administered. CONCLUSION: Patients who were instructed to chew gum after surgery demonstrated faster bowel function recovery and lower xerostomia grade after elective open liver resection than patients who did not chew gum. RELEVANCE TO CLINICAL PRACTICE: Gum-chewing is an inexpensive, helpful adjunct to standard postoperative care after liver resection. PMID- 22672010 TI - Registry of hemophilia and other bleeding disorders in Syria. AB - Creating a national registry for bleeding disorders is a major step in establishing a National Hemophilia Care Program in all countries. Creating such a registry which would contain accurate and regularly updated data, including laboratory analysis confirmed by a reference laboratory established at the Syrian Hemophilia Society. Blood samples were drawn and analysed in the Society reference laboratory for the following screening tests: prothrombin time (PT), APTT and coagulation factor assays. Inhibitor detection and VWF RiCof were performed depending on the result of the screening tests. HBs Ag, anti-HCV, anti HIV 1+2 and syphilis tests were also performed to detect transfusion transmitted agents (TTA). Diagnosis of the bleeding disorder type was confirmed for 760 of these cases. Among the 760 confirmed patients, 82.5% had haemophilia. Among these, 89.6%were haemophilia A; 10.4% were haemophilia B; 8.3% had VWD; 9.2% had other rare bleeding disorders as follows: 1.2% FVII deficiency, 0.7% FV deficiency, 1.8% F1 deficiency, 0.4% FX deficiency, 1.4% platelets dysfunctions (mainly Glanzmann Thrombasthenia) and 3.7% had combined FVIII and FV deficiency. Eighty (21.3%) cases of 375 screened for transfusion transmitted agents were positive for at least one infection: 0.5% were HBsAg positive, 19.7% were anti HCV positive, 0.8% had combined HBsAg and anti-HCV positivity and 0.3% was anti Syphilis positive. All patients were negative for HIV1 and HIV2. The preliminary data presented here follow known data on haemophilia A, haemophilia B and VWD disease. This registry will certainly help in improving haemophilia care in Syria. PMID- 22672011 TI - Characterization of MLS(b) resistance among Staphylococcus aureus and Staphylococcus epidermidis isolates carrying different SCCmec types. AB - This work characterizes MLS(b) resistance in 39 methicillin-resistant Staphylococcus aureus (MRSA) and 32 Staphylococcus epidermidis (MRSE) isolates. Of 21 erm(A) gene encoding MRSA isolates, 71.4% carried SCCmecIII, whereas of 12 isolates carrying the erm(C) gene, 83.3% carried SCCmecIV. Among the 25 MRSE isolates positive for the erm(C) gene, 80% had SCCmecIV or nontypeable cassettes. Isolates carrying these genes had MIC(90) >= 256 MUg/mL to erythromycin and clindamycin. The msr(A) gene was associated with a low MIC(90) to these drugs. The erm(A) gene was associated with SCCmecIII in MRSA isolates, whereas the erm(C) gene was associated with SCCmecIV in both MRSA and MRSE isolates. PMID- 22672012 TI - Vitamin K1-loaded lipid-core nanocapsules: physicochemical characterization and in vitro skin permeation. AB - BACKGROUND: The incorporation of substances in nanocarriers can modulate and/or manage their delivery profiles (immediate or sustained) and permeation through skin. Consequently, drug nanencapsulation intended for topical treatment can reduce the systemic absorption of the substance. OBJECTIVE: To obtain and characterize vitamin K1-loaded lipid core nanocapsules as well as to determine whether the nanoencapsulation influences the skin permeation of this vitamin. METHODS: The skin permeation study was performed by means of Franz-type diffusion cells followed by the tape stripping and retention techniques. The vitamin K1 loaded lipid core nanocapsules were obtained by the preformed polymer precipitation method and the particles were characterized. RESULTS: The nanocapsules presented average diameter of 211 +/- 2 nm, pH of 5.7 +/- 0.3, zeta potential of -14.9 +/- 0.6 mV and drug content of 10.2 mg/mL (102.1%). The physical stability of the nanocapsule suspension was verified using multiple light backscattering analysis. The amount of vitamin K1 in the dermis after 8 h of drug permeation was higher when the nanocapsules were applied compared to the control. Moreover, retention in the outermost skin layer and a decrease in the skin permeation to the receptor compartment due to the nanoencapsulation were observed. CONCLUSION: Thus, nanoencapsulation can lead to the selective permeation of vitamin K1 through the skin. PMID- 22672013 TI - Strategic design and refinement of Lewis acid-base catalysis by rare-earth-metal containing polyoxometalates. AB - Efficient polyoxometalate (POM)-based Lewis acid-base catalysts of the rare-earth metal-containing POMs (TBA(6)RE-POM, RE = Y(3+), Nd(3+), Eu(3+), Gd(3+), Tb(3+), or Dy(3+)) were designed and synthesized by reactions of TBA(4)H(4)[gamma SiW(10)O(36)] (TBA = tetra-n-butylammonium) with RE(acac)(3) (acac = acetylacetonato). TBA(6)RE-POM consisted of two silicotungstate units pillared by two rare-earth-metal cations. Nucleophilic oxygen-enriched surfaces of negatively charged POMs and the incorporated rare-earth-metal cations could work as Lewis bases and Lewis acids, respectively. Consequently, cyanosilylation of carbonyl compounds with trimethylsilyl cyanide ((TMS)CN) was efficiently promoted in the presence of the rare-earth-metal-containing POMs via the simultaneous activation of coupling partners on the same POM molecules. POMs with larger metal cations showed higher catalytic activities for cyanosilylation because of the higher activation ability of C?O bonds (higher Lewis acidities) and sterically less hindered Lewis acid sites. Among the POM catalysts examined, the neodymium containing POM showed remarkable catalytic performance for cyanosilylation of various kinds of structurally diverse ketones and aldehydes, giving the corresponding cyanohydrin trimethylsilyl ethers in high yields (13 substrates, 94 99%). In particular, the turnover frequency (714,000 h(-1)) and the turnover number (23,800) for the cyanosilylation of n-hexanal were of the highest level among those of previously reported catalysts. PMID- 22672015 TI - Errorless learning improves memory performance in children with acquired brain injury: a controlled comparison of standard and self-generation techniques. AB - The principle of errorless learning has proven efficacy in helping adults and older adults with acquired memory impairment learn novel information. However, surprisingly few studies have investigated its efficacy in children. The present study addresses this omission in the literature, investigating the effectiveness of two forms of errorless learning - the established method, in which the examiner provides responses during learning, and a self-generation method, in which learners produce their own responses - each relative to the standard baseline of trial-and-error learning, in young people with acquired brain injury (ABI, n = 15) and non-injured controls (n = 15). Participants learned different word lists in each condition and their memory was tested after distraction and, subsequently, after a 20-minute delay. Not surprisingly, controls performed better than the ABI group. However, while there was no effect of learning condition for controls, in the ABI group memory performance was significantly better under errorless conditions. In contrast to findings in the adult literature, there was no difference in the efficacy of the two errorless methods, suggesting that self-generation was no better than standard examiner-generation. This study extends upon previous research to provide the first demonstration of the effectiveness of errorless methods in a group of young people with ABI. PMID- 22672014 TI - Characteristics of cognitive function in early and late stages of amnestic mild cognitive impairment. AB - AIM: The detection of the early stages in amnesic mild cognitive impairment (aMCI) is considered important in diagnosing progression to Alzheimer's disease. The current study sought to investigate differences in cognitive function between control subjects with no memory loss (control), and subjects in the early stage of aMCI (EMCI) and late stage of aMCI (LMCI). METHODS: A total of 100 community dwelling older adults aged 65 years and over were recruited from 1543 potential subjects. Subjects were classified into three groups based on the degree of objective memory impairment; control (n=29), EMCI (n=34) and LMCI (n=37). Multiple neuropsychological tests were carried out to examine cognitive function. RESULTS: The EMCI individuals showed lower cognitive function relative to controls; not only in logical memory, but also in letter fluency (P<0.05). There were no significant differences in neuropsychological scores between the EMCI and LMCI groups, except for category fluency and logical memory. In addition, the EMCI subjects' logical memory score showed a significant relationship with letter fluency, category fluency and digit span backward test performance (P<0.05). CONCLUSIONS: These results suggest that the application of multiple neuropsychological tests might be useful in diagnosing older adults with EMCI and LMCI. PMID- 22672016 TI - The GCN2 homologue in Arabidopsis thaliana interacts with uncharged tRNA and uses Arabidopsis eIF2alpha molecules as direct substrates. AB - Phosphorylation of eIF2alpha is an important strategy for living organisms to adapt to metabolic and physiological changes that are often associated with external stimuli. GCN2 is one of the well-studied eIF2alpha kinases in yeast and mammals, which is responsible for the survival of the organism under amino acid starvation. Despite the downstream reactions being quite divergent, AtGCN2 exhibits a high primary sequence similarity to its yeast and animal counterparts. In this study, we provide experimental evidence to show that AtGCN2 shares similar biochemical properties to the yeast and animal homologues. Our in vitro assays demonstrate the binding of the C-terminus of AtGCN2 to uncharged tRNA molecules and the enzymatic activities of AtGCN2 on both eIF2alpha homologues in A. thaliana, thus providing essential information for further understanding the functions of plant general control non-repressible (GCN) homologues. PMID- 22672017 TI - Ultrafast proton transfer of three novel quinone cyanine photoacids. AB - Steady-state and time-resolved emission techniques were used to study the photoprotolytic properties of three recently synthesized strong quinone cyanine photoacids (QCy7 and its sulfonated derivatives). The rate coefficient of the excited-state proton transfer (ESPT), k(PT), of the three dyes is roughly 1.5 * 10(12) s(-1), a high value that is comparable to the solvation dynamics rate of large polar organic molecules in H(2)O and D(2)O. It is twice as fast as the proton transfer rate between two adjacent water molecules in liquid water. We found that, as expected, two of the sulfonated photoacids geminately recombines with the proton at an elevated rate. The accelerated geminate recombination process of the sulfonated derivatives is different from a simple diffusion process of protons. The ESPT rate coefficient of these molecules is the highest recorded thus far. PMID- 22672018 TI - Living donor liver transplantation in children: a single North American center experience over two decades. AB - Little data concerning hospital charges and long-term outcomes of LDLT in North American children according to transplant indications have been published. To compare outcomes of patient and graft survival and healthcare charges for LDLT for those with BA vs. other diagnoses (non-BA). A retrospective review of 52 children receiving 53 LDLT (38 BA and 14 non-BA) from 1992 to 2010 at our institution was performed. One-, five-, and 10-yr patient and graft survival data were comparable to national figures reported to UNOS. Average one-yr charges for recipients and donors were $242 849 for BA patients and $183 614 for non-BA (p = 0.074). BA patients were 1.23 +/- 1.20 yr of age vs. 4.25 +/- 5.02 for non-BA, p = 0.045. Examination of the total population of patients who were alive in 2010 in five chronological groupings showed that the crude five-yr survival rates were 1992-1995: 9/11 (82%); 1995-1997: 6/10 (60%); 1997-1999: 8/10 (80%); 1999-2001: 9/10 (90%); and 2001-2003: 7/7 (100%). Thus, examination of the clinical and financial data together over the entire period of the transplant program suggests that the dramatic improvement in patient survival was accomplished without a dramatic increase in indexed charges. All 53 donors survived, and only 10% had complications requiring hospitalization. LDLT in children results in excellent outcomes for patients and donors. Ways to lower costs and maximize graft outcome should be investigated. PMID- 22672019 TI - Pulmonary metastases: a rare manifestation of the most common cancer. AB - Basal cell carcinoma (BCC) is the most common human malignancy but rarely metastasises. We report on two patients with symptomatic lung metastases and a past history of recurrent BCC excisions. In our first patient, a heavy smoker with multiple lung lesions, histology of a resected nodule was first reported as non-small cell lung cancer but a repeat nodule biopsy a year later was recognised as a pulmonary metastasis from primary cutaneous BCC. Our second patient, a young never-smoker with two previous BCC, was confirmed as having a pulmonary metastasis from BCC on the lung resection specimen. Pulmonary metastasis from an unidentified primary site is a common clinical situation. These patients emphasise the importance of considering the most common cancer as a potential primary. PMID- 22672020 TI - Help yourself by helping us: responding to reviewers' comments. PMID- 22672022 TI - Writing an abstract: window to the world on your work. PMID- 22672023 TI - What drove us to drink 2 litres of water a day? PMID- 22672024 TI - The need to evaluate public health reforms: Australian perinatal mental health initiatives. AB - OBJECTIVE: To describe the Australian perinatal mental health reforms and explore ways of improving surveillance of maternal mental health morbidity and mortality in this context. APPROACHES: We reviewed the Australian perinatal (defined as conception to one year postpartum) mental health reforms, in association with an appraisal of the population health methods that could be used for their evaluation. CONCLUSION: Despite the increasing focus of public health reforms on maternal mental health in the perinatal period, there is currently no national data available to evaluate these reforms or to provide an evidence base for improved health outcomes. National data development and linkage of relevant datasets would go a long way towards enabling such an endeavour. IMPLICATIONS: Inclusion of key mental health items in the Perinatal National Minimum Dataset and use of data linkage techniques will allow for monitoring of trends in maternal mental health morbidity and mortality in response to the Australian reforms. Once this is implemented, cost-benefit analyses can be undertaken. PMID- 22672025 TI - Hospital-activity data inaccurate for determining spread-of-disease at diagnosis for non-small cell lung cancer. AB - OBJECTIVE: Accurate information on spread-of-disease at diagnosis would increase the usefulness of hospital-activity data for cancer research. This study evaluates the accuracy of codes recorded in hospital-activity data to assign spread-of-disease at diagnosis for non-small cell lung cancer (NSCLC). METHODS: The reference (gold) standard was TNM stage as assigned at a multi-disciplinary meeting. To allow comparison with hospital-activity data, TNM stage was mapped to spread-of-disease (local, regional, distant). Sensitivity, specificity and positive-predictive values were stratified by whether the patient had surgery. RESULTS: Data from the reference standard and hospital-activity database were available for 2,184 patients. According to the reference standard, local disease was present for 57.0% of surgical patients and 12.6% of non-surgical patients at diagnosis. Hospital-activity data over-estimated patients with local disease (surgical: 71.9%, non-surgical: 48.5%). There was a corresponding underestimation of distant spread-of-disease: surgical (reference standard: 4.0%, hospital activity data: 2.7%); non-surgical (reference standard: 45.9%, hospital-activity data: 36.8%). This meant that hospital-activity data had good sensitivity but poor specificity for local disease; and poor sensitivity, but good specificity for metastatic disease. CONCLUSION: Secondary diagnosis codes in hospital activity data do not accurately capture spread-of-disease at diagnosis for patients with non-small cell lung cancer; even when the clinical notes contain TNM clinical stage as documented at a multidisciplinary meeting. IMPLICATIONS: Changes are needed to coding rules, and the ICD codes themselves, to allow for coding of regional and distant spread without specification of the precise site. PMID- 22672026 TI - Differential loss of participants does not necessarily cause selection bias. AB - BACKGROUND: Most research is affected by differential participation, where individuals who do not participate have different characteristics to those who do. This is often assumed to induce selection bias. However, selection bias only occurs if the exposure-outcome association differs for participants compared to non-participants. We empirically demonstrate that selection bias does not necessarily occur when participation varies in a study. METHODS: We used data from three waves of the longitudinal Survey of Family, Income and Employment (SoFIE). We examined baseline associations of labour market activity and education with self-rated health using logistic regression in five participation samples: A) the original sample at year one (n=22,260); B) those remaining in the sample (n=18,360); C) those (at year 3) consenting to data linkage (n=14,350); D) drop outs over three years (n=3,895); and E) those who dropped out or did not consent (n=7,905). RESULTS: Loss to follow-up was more likely among lower socioeconomic groups and those with poorer health. However, for labour market activity and education, the odds of reporting fair/poor health were similar across all samples. Comparisons of the mutually exclusive samples (C and E) showed no difference in the odds ratios after adjustment for sociodemographic (participation) variables. Thus, there was little evidence of selection bias. CONCLUSIONS: Differential loss to follow-up (drop out) need not lead to selection bias in the association between exposure (labour market activity and education) and outcome (self-rated health). PMID- 22672027 TI - Capture-recapture using multiple data sources: estimating the prevalence of diabetes. AB - OBJECTIVE: To examine the potential for using multiple list sources and capture recapture methods for estimating the prevalence of diagnosed diabetes. METHOD: A model-averaging procedure using an adjusted Akaike's Information Criterion (QAICc) was used to combine capture-recapture estimates from log-linear models obtained from simultaneously analysing four sources of data. The method was illustrated using four separate lists of patients with diabetes, resident in Otago, New Zealand. RESULTS: Eighteen candidate models with a QAICc weight of more than 0.01 were obtained. A total of 5,716 individuals were enrolled on one or more of the four lists, of whom 379 (6.6%) appeared on all four lists and 1,670 (29.2%) appeared on one list only. The model-averaged estimate of the total number of people with diagnosed diabetes was 6,721 (95% CI: 6,097, 7,346). The age-standardised prevalence was 3.70% (95% CI: 3.36-4.04%) for the total population and 4.45% (95% CI: 4.03-4.86) for adults aged 15+ years. CONCLUSIONS: Estimated diabetes prevalence was consistent with national survey results. Capture-recapture methods, combined with model averaging, are a cheap, efficient tool to estimate the prevalence of diagnosed diabetes. IMPLICATIONS: This method provides a relatively easy way to estimate the prevalence of diagnosed diabetes using routinely collected diabetes information, thus providing the opportunity to monitor the diabetes epidemic and inform planning decisions and resource allocation. PMID- 22672028 TI - Geographic Information Systems used to describe the link between the risk of Ross River virus infection and proximity to the Leschenault estuary, WA. AB - OBJECTIVE: To investigate the relationship between risk of Ross River virus (RRV) infection and proximity to mosquito-breeding habitat surrounding a tidal wetland ecosystem in south-west Australia. METHODS: Geographic information systems (GIS) were used to spatially map cases of RRV disease in the Leschenault region between July 1995 and June 1996. Half kilometre buffer zones were constructed around the Leschenault Estuary and associated waterways; RRV disease case counts were calculated for each zone. RESULTS: Different relationships between RRV disease incidence and proximity to saltmarsh mosquito habitat were observed east of the Leschenault Estuary compared with an urban region to the south. Disease incidence showed a decreasing trend away from eastern margins of the Estuary, particularly for the first 2 km. In the urban region, RRV disease risk was low close to the Estuary, but increased further out and remained steady across the remainder of that region. CONCLUSIONS: The findings support an increased risk of contracting RRV disease for people residing close to eastern margins of the Leschenault Estuary. IMPLICATIONS: This study highlights how historical data combined with GIS can improve understanding of the epidemiology of RRV disease. This has a valuable role in assessing the risk of mosquito-borne disease for land-use planning. PMID- 22672029 TI - Most Australians do not meet recommendations for dairy consumption: findings of a new technique to analyse nutrition surveys. AB - OBJECTIVE: To describe the pattern of dairy consumption in Australians aged 12 years and over, and assess the extent to which the population meets national recommendations. METHODS: We developed a new method of combining quantitative data from a 24-hour dietary recall questionnaire with semiquantitative data from a food frequency questionnaire (FFQ), to investigate the usual patterns of dairy consumption. We applied this technique to data from the 9,096 Australians aged 12 and over who completed the FFQ part of the most recent nationally representative nutrition study - the 1995 National Nutrition Survey. RESULTS: When weighted according to the characteristics of the Australian population, 58% of male and 73% of female FFQ respondents failed to regularly meet recommendations for consumption of dairy products. While mean dairy consumption was higher in adolescents, 62% of boys and 83% of girls failed to meet their higher recommendation of three serves per day. Breastfeeding women appeared to consume more dairy but 60% consumed less than two serves per day. CONCLUSIONS AND IMPLICATIONS: Given accumulating evidence of protective effects of dairy foods for a range of metabolic and cardiovascular disorders, our observations warrant a focus on the development of cost-effective public health interventions to increase dairy consumption. PMID- 22672030 TI - The cost-effectiveness of falls prevention interventions for older community dwelling Australians. AB - OBJECTIVE: To evaluate the cost-effectiveness of strategies designed to prevent falls among older people. METHODS: A decision analytic Markov model of interventions designed to prevent falls was developed. Incremental cost effectiveness ratios (ICERs) using quality adjusted life year (QALYs) as the measure, were calculated for those interventions aimed at the general population (home exercise, group exercise, tai chi, multiple and multi-factorial interventions); high-risk populations (group exercise, home hazard assessment/modification and multi-factorial interventions); and specific populations (cardiac pacing, expedited cataract surgery and psychotropic medication withdrawal). Uncertainty was explored using univariate and probabilistic sensitivity analysis. CONCLUSION: In the general population, compared with no intervention the ICERs were tai chi ($44,205), group-based exercise ($70,834), multiple interventions ($72,306), home exercise ($93,432), multifactorial interventions with only referral ($125,868) and multifactorial interventions with an active component ($165,841). The interventions were ranked by cost in order to exclude dominated interventions (more costly, less effective) and extendedly dominated interventions (where an intervention is more costly and less effective than a combination of two other interventions). Tai chi remained the only cost-effective intervention for the general population. IMPLICATIONS: Interventions designed to prevent falls in older adults living in the community can be cost-effective. However, there is uncertainty around some of the model parameters which require further investigation. PMID- 22672031 TI - Paid parental leave supports breastfeeding and mother-infant relationship: a prospective investigation of maternal postpartum employment. AB - OBJECTIVE: To investigate the association between the mother-infant relationship, defined as maternal-infant emotional attachment, maternal separation anxiety and breastfeeding, and maternal employment status at 10 months following first childbirth. METHOD: Samples of employed, pregnant women, over 18 years of age and with sufficient English literacy were recruited systematically from one public and one private maternity hospital in Victoria. Data were collected by structured interview and self-report questionnaire in the third trimester, and at 3 and 10 months postpartum. Socio-demographic, employment, and breastfeeding information was collected. Participants completed standardised assessments of maternal separation anxiety and mother-to-infant emotional attachment. RESULTS: Of 205 eligible women, 165 (81%) agreed to participate and 129 (78%) provided complete data. A reduced odds of employment participation was independently associated with continuing to breastfeed at 10 months (OR=0.22, p=0.004) and reporting higher maternal separation anxiety (OR=0.23, p=0.01) when maternal age, education, occupational status and use of paid maternity leave and occupational status were adjusted for in analyses. CONCLUSION: Employment participation in the first 10 months postpartum is associated with lower maternal separation anxiety, and shorter breastfeeding duration. IMPLICATIONS: Paid parental leave has public health implications for mothers and infants. These include permitting sufficient time to protect sustained breastfeeding, and the development of optimal maternal infant attachment, reflected in confidence about separation from her infant. PMID- 22672032 TI - Diabetic retinopathy screening in New Zealand requires improvement: results from a multi-centre audit. AB - OBJECTIVE: To determine whether diabetic retinal screening services and retinopathy referral centres in New Zealand meet the national guidelines for referral and assessment of screen detected moderate retinal and mild macular diabetic eye disease. METHODS: Diabetic retinal screening pathways and the data collected at four main centre retinal screening services were described and compared with recommendations in the national diabetes retinal screening guidelines. A retrospective audit of photoscreen detected moderate retinopathy (grade R3), and mild maculopathy (grades M2B and M3) during May to August 2008 was undertaken. Data collected by retinopathy referral centres were used to examine the follow-up of screen detected cases and to make comparisons with the national recommendations. RESULTS: All four screening services used the guidelines for grading, but the recommended dataset was incomplete. Not all recorded data were readily accessible. The retinal photos of 157 (2.4%) patients were graded as R3, M2B, M3 or a combination. The proportion of those screened with these grades varied across the four centres from 1.2% to 3.4%. Follow-up of the 157 screen positive patients did not always comply with guideline recommendations. Seventy five (48%) were referred for review by an ophthalmologist as recommended, 45 (60% of referred) were seen within the recommended six months. Nine patients (15% of the 60 with a documented assessment) were referred for or received laser treatment at 12-months follow-up. CONCLUSION: Quality diabetic retinal screening data systems and quality assurance programs are required to improve the monitoring and quality of retinal screening in New Zealand. PMID- 22672033 TI - A 'whole of system' approach to compare options for CVD interventions in Counties Manukau. AB - OBJECTIVE: To assess the usefulness of a national and a local system dynamics model of cardiovascular disease to planning and funding decision makers. METHODS: In an iterative process, an existing national model was populated with local data and presented to stakeholders in Counties Manukau, New Zealand. They explored the model's plausibility, usefulness and implications. Data were collected from 30 people using questionnaires, and from field notes and interviews; both were thematically analysed. RESULTS: Potential users readily understood the model and actively engaged in discussing it. None disputed the overall model structure, but most wanted extensions to elaborate areas of specific interest to them. Local data made little qualitative difference to data interpretation but were nevertheless considered a necessary step to support confident local decisions. CONCLUSION: Some limitations to the model and its use were recognised, but users could allow for these and still derive use from the model to qualitatively compare decision options. IMPLICATIONS: The system dynamics modelling process is useful in complex systems and is likely to become established as part of the routinely used suite of tools used to support complex decisions in Counties Manukau District Health Board. PMID- 22672034 TI - A bibliometric analysis of research on Indigenous health in Australia, 1972-2008. AB - OBJECTIVE: To determine the growth patterns and citation volume of research publications referring to Indigenous health in Australia from 1972 to 2008 compared to seven selected health fields. METHODS: Web of Science was used to identify all publications (n=820) referring to the health of Indigenous Australians authored by Australian researchers, 1972 to 2008. Citations for each publication were also captured. Growth was compared with selected health fields as well as with overall Australian research publications. RESULTS: Research publications referring to Indigenous health, while remaining relatively small in number, grew at an average annual rate of 14.1%, compared with 8.2% across all fields of Australian research. The growth rate shown was equal second highest in our seven categories of health and medical research. However, Indigenous publications were cited significantly less than the Australian average. CONCLUSIONS: While there has been positive growth in publications referring to Indigenous health, the attention paid to this research through citations remains disappointingly low. IMPLICATIONS: Given that research concentration and impact can be an index of how seriously a nation considers a health problem, the low visibility of Australian research examining Indigenous health does not demonstrate a level of concern commensurate with the gravity of Indigenous health problems. Further investigation for the reasons for lower citations may identify potential intervention strategies. PMID- 22672035 TI - Increased mortality among Indigenous persons during and after release from prison in New South Wales. AB - OBJECTIVE: To estimate the overall and cause specific mortality of Aboriginal offenders in New South Wales (NSW), Australia. METHODS: The study cohort consisted of all Aboriginal men and women aged 18 years and older who had experienced full-time imprisonment in NSW between 1 January 1988 and 31 December 2002. Their data were linked probabilistically to the Australian National Death Index to obtain information on death. Standardised mortality ratios were calculated for all causes of death and adjusted for age, sex, and calendar year. RESULTS: The cohort comprised 7,980 men and 1,373 women with 75,801 person years of observation. During a median follow-up period of 8.3 years, 485 men and 73 women died, giving an overall mortality rate of 733 and 755 deaths per 100,000 person-years. The risk of death in men was 4.8 (95% CI: 4.4-5.3) times and among women 12.6 (95% CI: 10.0-15.8) times that of the NSW residents, with a markedly elevated risk for almost all conditions. The leading cause of death was cardiovascular disease in men (112 deaths, 23%) and mental and behavioural disorders (17 deaths, 23%) in women. The risk of death was greatest following release from prison. CONCLUSIONS AND IMPLICATIONS: High mortality rates for cardiovascular disease, a preventable and treatable condition, were seen among Aboriginal offenders. Prison has an important role to play in screening marginalised populations for a range of health conditions. This is particularly true for Indigenous offenders. PMID- 22672036 TI - Can we count? Enumerating births in two remote Aboriginal communities in the Northern Territory. AB - OBJECTIVE: To examine the accuracy of birth counts for two remote Aboriginal communities in the Top End of the Northern Territory. METHODS: We compared livebirth counts from community birth records with birth registration numbers and perinatal counts. RESULTS: For 2004-06, for Community 1, there were 204 recorded local livebirths, 190 birth registrations and 172 livebirths in perinatal data. In Community 2, the counts were 244, 222 and 208, respectively. The mean annual number of babies, indicating service requirements for babies and their mothers, ranged from 57 to 68 (depending on source) in Community 1, and from 69 to 81 in Community 2. Most differences were for births to Aboriginal mothers. Births to 'visitors' accounted for 16 births in Community 1 and 30 cases in Community 2. CONCLUSION: Birth registration and perinatal data apparently underestimate community birth counts at a local level. Mobility of Aboriginal women seems to partly explain this. IMPLICATIONS: The differences in birth counts have important implications for local planning in relation to demand on housing, health and education services. The number of births is also a critical data requirement for measuring infant health status, including mortality rates, with measures of disadvantage strongly influenced by the number of births. Aboriginal mobility is not a 'data problem', but an integral part of Aboriginal life that needs to be catered for in administrative data collections in the Northern Territory. PMID- 22672037 TI - South Australian four-year-old Aboriginal children: residence and socioeconomic status influence weight. AB - OBJECTIVE: Obesity rates have increased in children in Australia in the past 15 years. However, there is little available population data describing rates of overweight and obesity in Aboriginal children. METHODS: Anthropometric data of four-year-old children (n=11,859) were collected by trained nurses at routine statewide preschool health checks during 2009. Weight status (underweight, healthy weight, overweight and obese) was determined using age and gender specific International Obesity Task Force (IOTF) cut-points. RESULTS: There were 337 Aboriginal children (3%) in the study population. Aboriginal children had significantly higher rates of overweight and obesity compared to non-Aboriginal children (28% compared to 18% respectively, chi(2) p=0.0001). A statistically significant association between BMIz score and identifying as Aboriginal remained after controlling for rural/urban residence and socioeconomic status using multiple regression analyses. CONCLUSIONS: Aboriginal children have higher rates of overweight and obesity compared to their non-Aboriginal peers by the time they are four years of age. Aboriginal children have higher BMIz scores compared to non-Aboriginal children after controlling for rural/urban residence and socioeconomic status. IMPLICATIONS: A significant investment is required to optimise the health of Aboriginal women before pregnancy and throughout pregnancy. A rethink may be necessary in the approach to dietary management and catch-up growth of Aboriginal children of low birth weight or having growth failure in early childhood. PMID- 22672038 TI - Loose tobacco, ethnicity, income and rurality. PMID- 22672039 TI - Healthy organisations are associated with healthy employees: results of a cross sectional study. PMID- 22672040 TI - Ecologic fallacy and the social ecology of circumcision. PMID- 22672041 TI - Acceptability of proactive telephone recruitment to a telephone support service to encourage healthy eating, physical activity and weight loss. PMID- 22672042 TI - Support for vulnerable people during heat waves: a response to Stuart et al. PMID- 22672043 TI - Student Aboriginal health worker smoking: findings from a training college in Western Australia. PMID- 22672044 TI - Dental caries and dental fluorosis in children on the NSW Central Coast: a cross sectional study of fluoridated and non-fluoridated areas. PMID- 22672045 TI - Coeliac disease in Type 1 diabetes from 1990 to 2009: higher incidence in young children after longer diabetes duration. AB - AIMS: To determine the incidence of coeliac disease in young people with Type 1 diabetes and to examine the effect of age at diabetes onset and disease duration. METHODS: This was a clinic-based observational cohort study of 4379 people aged <= 18 years (49% male) between 1990 and 2009 from Sydney, Australia. Screening for coeliac disease was performed at diagnosis and 1-2 yearly using anti endomysial and/or anti-tissue transglutaminase immunoglobulin A (IgA) antibodies. Coeliac disease was diagnosed by small bowel biopsy based on Marsh score >= III. RESULTS: Coeliac disease was confirmed by biopsy in 185; of these, 61 (33%) were endomysial or tissue transglutaminase IgA antibody-positive at diabetes diagnosis. Mean age at diabetes onset was 6.6 +/- 4.0 vs. 8.4 +/- 4.1 years in those without coeliac disease (P < 0.001). Mean incidence was 7.7 per 1000 person years (95% CI 6.6-8.9) over 20 years. Incidence was higher in children aged < 5 years at diabetes diagnosis (10.4 per 1000 person years) vs. >= 5 years (6.4 per 1000), incidence rate ratio 1.6 (95% CI 1.2-2.2, P = 0.002). Coeliac disease was diagnosed after 2, 5 and 10 years of diabetes in 45, 78 and 94% of cases, respectively. Median time to coeliac disease diagnosis was longer in children aged < 5 years at diabetes onset (3.3 years) compared with older children (0.7 years, P < 0.001). CONCLUSIONS: Coeliac disease is common in young people with Type 1 diabetes; the risk is greatest with diabetes onset < 5 years, but after longer diabetes duration. Screening for coeliac disease should be performed at diabetes diagnosis and for at least 10 years in young children. PMID- 22672046 TI - Deletion and acquisition of genomic content during early stage adaptation of Pseudomonas aeruginosa to a human host environment. AB - Adaptation of bacterial pathogens to a permanently host-associated lifestyle by means of deletion or acquisition of genetic material is usually examined through comparison of present-day isolates to a distant theoretical ancestor. This limits the resolution of the adaptation process. We conducted a retrospective study of the dissemination of the P.aeruginosa DK2 clone type among patients suffering from cystic fibrosis, sequencing the genomes of 45 isolates collected from 16 individuals over 35 years. Analysis of the genomes provides a high-resolution examination of the dynamics and mechanisms of the change in genetic content during the early stage of host adaptation by this P.aeruginosa strain as it adapts to the cystic fibrosis (CF) lung of several patients. Considerable genome reduction is detected predominantly through the deletion of large genomic regions, and up to 8% of the genome is deleted in one isolate. Compared with in vitro estimates the resulting average deletion rates are 12- to 36-fold higher. Deletions occur through both illegitimate and homologous recombination, but they are not IS element mediated as previously reported for early stage host adaptation. Uptake of novel DNA sequences during infection is limited as only one prophage region was putatively inserted in one isolate, demonstrating that early host adaptation is characterized by the reduction of genomic repertoire rather than acquisition of novel functions. Finally, we also describe the complete genome of this highly adapted pathogenic strain of P.aeruginosa to strengthen the genetic basis, which serves to help our understanding of microbial evolution in a natural environment. PMID- 22672047 TI - A cross-talk of decidual stromal cells, trophoblast, and immune cells: a prerequisite for the success of pregnancy. AB - Embryo implantation and formation of a functional placenta are complex processes that require a plethora of regulatory mechanisms involving both mother and embryo cells. Recently, an important role in this complicated cells and factors network was assigned to the decidual stromal cells (DSC) and trophoblast cells. Decidualization includes biochemical changes that trigger DSC to produce a number of factors required for the implantation and induction of immunotolerance in maternal immune system. Immunotolerance is achieved by a cascade of strictly controlled events starting with selective homing of immune cells to the feto maternal site, regulated proliferation, and predominant differentiation into a regulatory type of immune cells. Furthermore, cytotoxic effector functions are reduced owing to the influence of steroid hormones, factors, cytokines, and inhibitory receptors. Altogether the entire immune system of the mother is switched to tolerogenic functional state which is a prerequisite for the successful maintenance of pregnancy. PMID- 22672048 TI - In vivo imaging reveals novel aspects of retinal disease progression in Rs1h(-/Y) mice but no therapeutic effect of carbonic anhydrase inhibition. AB - PURPOSE: X-linked juvenile retinoschisis (XLRS) is the most common juvenile maculopathy in men and is caused by mutations in the gene encoding retinoschisin (RS1). Evidence in the literature on the therapeutic effect of carboanhydrase inhibitors (CAIs) to treat schisis formation in the retina has remained equivocal. Here, we evaluate the effect of the CAI dorzolamide on the structural and functional disease progression in the mouse model for XLRS (Rs1h(-/y)). METHODS: Rs1h (-/y) mice were treated unilaterally with dorzolamide eye drops (Trusopt((r)) 20 mg/mL) every 12 h for 2 weeks starting on postnatal day 14 (n = 27). Changes of retinal structure were monitored by confocal scanning laser ophthalmoscopy and spectral domain optical coherence tomography 12 h, 14 days, 4 weeks, 2 months, and 6 months after completion of the treatment. RESULTS: Schisis formation (peak at 3 months) preceded photoreceptor degeneration and hyper fluorescence (peak at 7 months). Structural pathology was most severe in the superior hemi-retina with previously unreported hyper-fluorescent lesions. Quantitative analysis showed no significant differences regarding the inner or outer retinal thickness of the treated vs. untreated eyes 12 h after the completion of treatment (IRT(12 h) = -1.29 +/- 1.89 MUm; ORT(12 h) = 0.61 +/- 2.08 MUm; mean +/- 95%CI) or at any later time point. CONCLUSION: Time line analysis after short-term treatment with CAI failed to show short-, intermediate , or long-term evidence of structural improvement in Rs1h(-/y) mice. Schisis formation in the inner retina peaked at the age of 3 months and was followed by photoreceptor degeneration predominantly in the superior hemi-retina. Previously unreported hyper-fluorescent lesions co-register with structural retinal pathologies. PMID- 22672049 TI - The failed and future promise of intraspinal drug administration for neurologic disorders. PMID- 22672050 TI - Neurotech report. PMID- 22672051 TI - Linguistic testing during ON/OFF states of electrical stimulation in the associative portion of the subthalamic nucleus. AB - INTRODUCTION: Long-term studies of subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with Parkinson's disease have shown potential cognitive and linguistic side-effects. In this pilot study, we examined whether direct monopolar stimulation in the ventral, associative STN would result in language effects. METHODS: Three subjects participated in two linguistic tasks targeting language generation (language samples) and language composition (syntactic/grammatical structures). All subjects were tested in ON-/OFF associative stimulation settings. The subjects' Unified Parkinson's Disease Rating Scale scores in ON/OFF medication were taken; all subjects' scores indicated that DBS would be beneficial. Testing was conducted in the associative STN at varying stimulation settings of amplitude (80% of previously determined side-effect threshold), pulse width, and frequency. RESULTS: Linguistic functioning was affected by electrical stimulation to the associative STN. The data reflected a general decline in linguistic functioning in the ON stimulation setting. CONCLUSION: Our data support previous findings implicating STN stimulation in cognitive-linguistic effects. A larger patient group with a blinded methodology is warranted. PMID- 22672052 TI - Pain management in postherpetic neuralgia: emerging new therapeutic options besides spinal cord stimulation. PMID- 22672053 TI - Encourage disregard. PMID- 22672055 TI - Contagious flexibility? A study on whether schedule flexibility facilitates work life enrichment. AB - Schedule flexibility defines an important generating resource for work-life enrichment; however, our knowledge about how such spillovers take place is limited. This multiple case study examines how workers from different working time contexts with varying levels of schedule flexibility experience work-life interplay. Given the adopted explorative design, it is important to interpret the findings in a tentative light. Nonetheless, the study offers important insight into work-life enrichment that may guide future research in this field. The findings indicate that schedule flexibility may act as a boundary-spanning resource owing to the agency potential it offers workers. Thus, it seemed that flexible schedule opportunities enabled workers to engage more fully in personal life activities, which in turn had a positive influence on their work involvement through positive affect. Such positive role engagements appeared, however, to be greatly determined by workers' boundary management and by time conditions of work and family. In conclusion, the major findings and limitation of the study are discussed against existing research and theory. PMID- 22672056 TI - Intravenous injection of indocyanine green to enhance laser-assisted coagulation of blood vessels in skin - an animal study. AB - BACKGROUND: Laser therapy of vascular lesions, such as port wine stains (PWS) or leg veins are still imperfect due to different diameters and depth of vessels in tissue. We propose to improve blood vessel coagulation by intravenous introduction of an exogenous chromophore (indocyanine green, ICG) that effectively converts near-infrared (NIR) laser light into heat. OBJECTIVE: The purpose of this study was to determine the plasma clearance rate, systemic toxicity and histological effects of ICG-assisted laser therapy in an animal model. METHODS: Piglets received intravenous injection of ICG. Blood samples were collected at different times. Systemic toxicity was assessed by measuring liver enzyme levels and other indicators of liver function. The plasma clearance rate of ICG was determined by light absorption measurement in blood samples. The skin was irradiated with a diode laser (810 nm) using radiant exposures from 31 to 80 J/cm2. Skin reaction at the treatment site was graded, and punch biopsies were taken for histological examination at 24 and 72 h after treatment. RESULTS: No hepatic toxicity was observed. The clinical examination revealed no adverse skin reactions at 24 or 72 h after laser irradiation. This was confirmed by histological evaluation that showed efficient vessel coagulation without damage of the epidermis or dermis. CONCLUSIONS: In light of these in vivo results, we suggest that ICG-assisted laser therapy could substantially improve clinical outcomes of PWS or leg veins treatment with minimal risk of adverse reactions. PMID- 22672058 TI - Evaluation of digestive tolerance of a soluble corn fibre. AB - BACKGROUND: To assess consumers' acceptance of a new fibre, it is essential to evaluate its digestive tolerance after ingestion. We aimed to determine the tolerance of increasing dosages of PromitorTM Soluble Gluco Fibre (SGF; Tate&Lyle, Hoffman Estates, IL, USA) up to 70 g fibre per day using a validated gastrointestinal composite score. METHODS: A composite score of gastrointestinal tolerance integrating gastrointestinal symptoms, stool frequency and consistency was applied. To statistically validate this composite score, the gastrointestinal tolerance of inulin (10 g versus 20 g containing, respectively, 9 g versus 18 g of fibre) was assessed in 18 healthy volunteers in a randomised double-blind placebo-controlled cross-over study. Second, in a double-blind placebo-controlled cross-over study with 20 healthy volunteers, the gastrointestinal tolerance of SGF in both acute and 'spread over the day' conditions of consumption was assessed. RESULTS: By contrast to 10 g, 20 g of inulin demonstrated a significant difference in composite score compared to placebo [P < 0.001, difference = 7.6; 95% confidence interval (CI) = 3.8-11.3]. These values were considered as reference during the second study. In acute conditions, 40 g of SGF fibre was the highest (threshold) dose tested that indicates the digestive tolerance criteria (difference from placebo on the composite score <7.6 and upper limit of the 95% CI <11.3); this is twice the amount tolerated for inulin. In 'spread over the day' conditions, 65 g of SGF fibre was the threshold dose (P < 0.001, difference = 6.5; 95% CI = 3.4-9.5). CONCLUSIONS: The results of the present study demonstrate that 40 g of SGF fibre, when consumed as a single dose, and 65 g of SGF fibre, when consumed in multiple-doses, across the day are well-tolerated by healthy volunteers. PMID- 22672059 TI - The use of a rigid disc to protect exposed structures in wounds treated with negative pressure wound therapy: effects on wound bed pressure and microvascular blood flow. AB - There are increasing reports of deaths and serious complications associated with the use of negative pressure wound therapy (NPWT). Bleeding may occur in patients when NPWT is applied to a wound with exposed blood vessels or vascular grafts, possibly due to mechanical deformation and hypoperfusion of the vessel walls. Recent evidence suggests that using a rigid barrier disc to protect underlying tissue can prevent this mechanical deformation. The aim of this study was to examine the effect of rigid discs on the tissue exposed to negative pressure with regard to tissue pressure and microvascular blood flow. Peripheral wounds were created on the backs of eight pigs. The pressure and microvascular blood flow in the wound bed were measured when NPWT was applied. The wound was filled with foam, and rigid discs of different designs were inserted between the wound bed and the foam. The discs were created with or without channels (to accommodate exposed sensitive structures such as blood vessels and nerves), perforations, or a porous dressing that covered the underside of the discs (to facilitate pressure transduction and fluid evacuation). When comparing the results for pressure transduction to the wound bed, no significant differences were found using different discs covered with dressing, whereas pressure transduction was lower with bare discs. Microvascular blood flow in the wound bed decreased by 49 +/- 7% when NPWT was applied to control wounds. The reduction in blood flow was less in the presence of a protective disc (e.g., -6 +/- 5% for a dressing-covered, perforated disc, p = 0.006). In conclusion, NPWT causes hypoperfusion of superficial tissue in the wound bed. The insertion of a rigid barrier counteracts this effect. The placement of a rigid disc over exposed blood vessels or nerves may protect these structures from rupture and damage. PMID- 22672060 TI - Case of Kindler syndrome resulting from mutation in the FERMT1 gene. PMID- 22672057 TI - Suppression of premature termination codons as a therapeutic approach. AB - In this review, we describe our current understanding of translation termination and pharmacological agents that influence the accuracy of this process. A number of drugs have been identified that induce suppression of translation termination at in-frame premature termination codons (PTCs; also known as nonsense mutations) in mammalian cells. We discuss efforts to utilize these drugs to suppress disease causing PTCs that result in the loss of protein expression and function. In-frame PTCs represent a genotypic subset of mutations that make up ~11% of all known mutations that cause genetic diseases, and millions of patients have diseases attributable to PTCs. Current approaches aimed at reducing the efficiency of translation termination at PTCs (referred to as PTC suppression therapy) have the goal of alleviating the phenotypic consequences of a wide range of genetic diseases. Suppression therapy is currently in clinical trials for treatment of several genetic diseases caused by PTCs, and preliminary results suggest that some patients have shown clinical improvements. While current progress is promising, we discuss various approaches that may further enhance the efficiency of this novel therapeutic approach. PMID- 22672061 TI - Self-assembled three-dimensional nanocrown array. AB - Although an ordered nanoplasmonic probe array will have a huge impact on light harvesting, selective frequency response (i.e., nanoantenna), and quantitative molecular/cellular imaging, the realization of such an array is still limited by conventional techniques due to the serial processing or resolution limit by light diffraction. Here, we demonstrate a thermodynamically driven, self-assembled three-dimensional nanocrown array that consists of a core and six satellite gold nanoparticles (GNPs). Our ordered nanoprobe array is fabricated over a large area by thermal dewetting of thin gold film on hexagonally ordered porous anodic alumina (PAA). During thermal dewetting, the structural order of the PAA template dictates the periodic arrangement of gold nanoparticles, rendering the array of gold nanocrown. Because of its tunable size (i.e., 50 nm core and 20 nm satellite GNPs), arrangement, and periodicity, the nanocrown array shows multiple optical resonance frequencies at visible wavelengths as well as angle-dependent optical properties. PMID- 22672062 TI - The development of measurement tools for prosthetic eye research. AB - BACKGROUND: The aim was to develop tools to measure the condition of ocular prostheses and the socket's response to prosthetic eyewear. METHODS: A novel staining technique for displaying deposits on prosthetic eyes was developed. Equal interval perceptual grading scales for measuring inferior palpebral conjunctival inflammation, and anterior and posterior stained surface deposits on prosthetic eyes were developed from 800 photographs of 43 volunteers. The photographs for each scale were chosen by the authors. A group of four ophthalmologists, three optometrists and three senior students was consulted about selection criteria and asked to position the photographs along a 1.5 m rule to determine equal intervals. Photographs judged not to represent exactly equal perceptual intervals were exchanged with others from the original pool. The final scales (a five-photograph scale for inflammation and two 11 photograph scales for deposits) were assessed for inter-rater reliability and test-retest reliability by groups of senior optometry students. RESULTS: Standard deviations for inter rater reliability tests were 0.52 scale units for the inflammation scale, 0.99 for the anterior surface deposits scale and 1.03 for the posterior surface deposits scale. The standard deviation of the test-retest differences for inflammation was 0.6 scale units and for both anterior and posterior surface deposits it was 0.71. CONCLUSIONS: A novel technique for displaying and measuring the intensity and extent of deposit formation on prosthetic eye surfaces has been described. The two equal interval perceptual grading scales that have been developed to quantify the extent of deposit formation together with the equal interval perceptual scale for grading severity of palpebral conjunctival inflammation will for the first time allow the effects of prosthetic eye wear to be evaluated. Further research to validate the scale for palpebral conjunctival inflammation in a clinical setting is recommended. The technique for staining deposits on prosthetic eyes is recommended for clinical practice. PMID- 22672063 TI - Development and validation of the Family Meaning of Nursing-Home Visits Scale. AB - AIMS AND OBJECTIVES: The purpose of this study was to develop and test a Family Meaning of Nursing-Home Visits Scale that can be used to assess and document family members' rationale for visiting nursing home residents. BACKGROUND: Understanding the meaning ascribed by families for visiting nursing home residents is necessary to develop intervention programmes that facilitate the quality of families' nursing home visits. No valid and reliable instrument is available in Taiwan or elsewhere to accurately document the meaning of family visits to nursing home residents. DESIGN: A cross-sectional design was used to collect survey data from family members of nursing home residents as the quantitative component of a mixed-methods study. Items were developed based on qualitative data from our previous research and that of others. This initial pool of items was used to develop and validate the scale. METHODS: The validity of the scale was confirmed by exploratory factor analysis and criterion-related validity testing. Internal consistency reliability was assessed by Cronbach's alphas. RESULTS: Factor analysis yielded a six-factor final solution (32 items), accounting for 66.76% of the variance. For criterion-related validity, 'responsibility for care quality' was negatively correlated with satisfaction with nursing home caregiving (r = -0.23, p < 0.01) and nursing home rehabilitation activities (r = -0.17, p < 0.05). Cronbach's alpha for each subscale ranged from 0.68-0.98, and Cronbach's alpha for the total scale was 0.83. CONCLUSIONS: The Family Meaning of Nursing-Home Visits Scale has acceptable internal consistency reliability, good content validity and acceptable construct validity. RELEVANCE TO CLINICAL PRACTICE: The Family Meaning of Nursing-Home Visits Scale provides nurses and healthcare providers an objective and consistent method to explore the priority of meanings family members assign to nursing home visits. Based on this priority for visiting, interventions could be designed to increase the quality of visits, thus promoting families' continued incentive to visit in person. PMID- 22672064 TI - Skin integrity testing and monitoring of in vitro tape stripping by capacitance based sensor imaging. AB - BACKGROUND: Despite the frequent use of porcine ear skin for tape-stripping experiments, the peculiarities of this skin type have not been characterised in detail yet. Thus, different techniques were employed to investigate the skin surface structure of porcine ear skin and the changes in barrier function during in vitro tape stripping. To this end, the potential of capacitance-based skin hydration imaging as a means of skin quality control was investigated for the first time. METHODS: The porcine ear model was characterised before and during tape stripping using transepidermal water loss (TEWL) measurements, capacitance based sensor imaging, attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) and optical light microscopy. RESULTS: The capacitance based sensor was found to deliver precise information about the quality of the employed skin sites before and during tape stripping. The removal of stratum corneum proteins was highly reproducible even for different porcine ear types. The mean greyscale values showed an excellent linear correlation to the corresponding TEWL values and the respective penetration depth. Optical light microscopy confirmed the presence of canyons on the surface of porcine ear skin. CONCLUSION: The results suggest that the capacitance-based sensor is a suitable tool for skin integrity testing of porcine ear skin in vitro and for monitoring changes in skin barrier function. PMID- 22672065 TI - Endophytic Chaetomium globosum enhances maize seedling copper stress tolerance. AB - This study aims at characterisation of the impact of Chaetomium globosum on copper stress resistance of maize seedlings. Higher levels of copper treatment decreased maize dry weight and induced a marked increase in osmotic solutes, antioxidant enzyme activity and the level of lipid peroxidation. On the other hand, addition of the endophytic C. globosum alleviated the toxic effect of copper on maize growth. The combination of copper sulphate and Chaetomium increased seedling dry weight, osmotic solute content and antioxidant enzyme activity compared to copper sulphate alone, while lipid peroxidation levels were also decreased. The fungal scavenger system might be important for supporting the ability of maize seedlings to resist copper toxicity. PMID- 22672066 TI - Experience of recombinant activated factor VII usage during surgery in patients with haemophilia with inhibitors. AB - Inhibitor development is one of the most challenging complications of haemophilia management. Haemostatic control in patients with haemophilia with inhibitors can be difficult, and is especially risky in those undergoing surgical interventions. Most haemophilia patients with inhibitors suffer from chronic joint disease requiring surgical correction due to recurrent bleeding episodes. The aim of this study was to assess the use of recombinant activated factor VII (rFVIIa) as haemostatic therapy during orthopaedic surgery in haemophilia patients with inhibitors. A series of case reports was retrospectively collected to describe clinical experience of rFVIIa use in inhibitor patients undergoing a range of orthopaedic surgical procedures at a single centre. All surgeries were performed using standard methods. All patients received rFVIIa at a starting dose of 120 MUg kg(-1) with the subsequent regimens depending on the type of surgery. rFVIIa provided effective haemostasis in 23 patients with haemophilia A and inhibitors (15 with high inhibitor titres) undergoing orthopaedic surgery. The majority (70%) of surgical procedures were major (joint and extra-articular surgery). The doses and intervals of rFVIIa treatment used varied depending on the severity of bleeding, and the type (major or minor) or site of surgery. In all cases, administration of rFVIIa achieved good haemostasis. In all 23 patients with haemophilia with inhibitors, rFVIIa treatment in orthopaedic interventions proved to be an efficient haemostatic agent, providing effective intra-operative and postoperative haemostasis. PMID- 22672067 TI - The increased prevalence of non-alcoholic fatty liver disease in psoriatic patients: a study from South India. AB - BACKGROUND: Psoriasis is an inflammatory disease of the skin and joints. Previous studies have shown a higher prevalence of metabolic syndrome (MS) in psoriatic patients. Recent studies show that non-alcoholic fatty liver disease (NAFLD) is also frequent in psoriasis patients. OBJECTIVES: To investigate the occurrence and severity of NAFLD in South Indian psoriatic patients and healthy controls. METHODS: In phase 1 we performed a case control study on 333 adult psoriasis patients and 330 controls matched by age, sex and body mass index. NAFLD was diagnosed by ultrasonography and liver enzymes after excluding other liver diseases. In phase 2 we compared the NAFLD subgroups in psoriasis patients and controls by determining their fibrosis, steatosis and non-alcoholic steatohepatitis (NASH) scores. RESULTS: The occurrence of NAFLD was higher in psoriasis patients than in controls (17.4 vs 7.9%; P = 0.002). NAFLD patients in the psoriasis group (n = 58) were more likely to have MS (P = 0.03) and diabetes (P = 0.02) than those with psoriasis alone (n = 254). The former group had a longer duration of psoriasis and arthritis (P = 0.003 and 0.005). Psoriasis patients with NAFLD had more severe disease as per the psoriasis area and severity index scores (P = 0.02). Psoriasis patients had more severe NAFLD than controls as reflected by the steatosis, NASH and fibrosis scores (P = 0.001, 0.003, 0.03 respectively). CONCLUSION: NAFLD is the commonest liver disease in Indian psoriatic patients when compared to controls. As NAFLD is more severe in psoriasis patients we suggest routine screening for NAFLD in this group especially when systemic therapy is considered. PMID- 22672068 TI - Use of the Multiple Errands Test-Simplified Version in the assessment of suboptimal effort. AB - Most measures of suboptimal effort focus on short-term learning; fewer studies have considered non-memory feigned cognitive impairment. This study investigated the utility of the Multiple Errands Test - Simplified Version (MET-SV) in the detection of feigned executive functioning impairment. Performance of simulating malingerers (N = 47) was compared to acquired brain injury (N = 46) and neurologically healthy control groups (N = 50). Although simulating malingerers were successful at feigning a realistic level of impairment compared to the brain injury group, there were significant differences regarding pattern of performance. A logistic regression model successfully classified 84% of simulating malingerers and 74.5% of brain injured individuals. Receiver Operating Characteristic (ROC) analysis supported the discriminatory power of the model. The current study is unique in yielding some understanding of the real-life observation of suspected malingerers compared to individuals with genuine cognitive difficulties. Results suggest the MET-SV can contribute to the clinical assessment of individuals suspected of suboptimal effort in the domain of executive functioning. Further research is needed to establish whether the MET-SV can be reliably used in medico-legal settings. PMID- 22672069 TI - New reaction model for O-O bond formation and O2 evolution catalyzed by dinuclear manganese complex. AB - A new mechanism of the oxygen evolving reaction catalyzed by [H(2)O(terpy)Mn(MU O)(2)Mn(terpy)OH(2)](3+) is proposed by using density functional theory. This proton coupled electron transfer (PCET) model shows reasonable barriers. Because in experiments excess oxidants (OCl(-) or HSO(5)(-)) are required to evolve oxygen from water, we considered the Mn(2) complex neutralized by three counterions. Structure optimization made the coordinated OCl(-) withdraw a H(+) from the water ligand and produces the reaction space for H(2)O(2) formation with the deprotonated OH(-) ligand. The reaction barrier for the H(2)O(2) formation from OH(-) and protonated OCl(-) depends significantly on the system charge and is 14.0 kcal/mol when the system is neutralized. The H(2)O(2) decomposes to O(2) during two PCET processes to the Mn(2) complex, both with barriers lower than 12.0 kcal/mol. In both PCET processes the spin moment of transferred electrons prefers to be parallel to that of Mn 3d electrons because of the exchange interaction. This model thus explains how the triplet O(2) molecule is produced. PMID- 22672070 TI - Late-onset bloodstream infections in preterm infants: a 2-year survey. AB - BACKGROUND: We determined the prevalence and risk factors for late-onset bloodstream infections (LO-BSI), the distribution of pathogens and the outcomes of affected preterm infants. METHODS: The records of all preterm infants (<37 weeks gestation) born between 2004 and 2005 and hospitalized in the neonatal intensive care unit for >3 days were retrieved for this retrospective matched case-control study. RESULTS: A total of 108 out of 1459 preterm infants (7.4%) had 142 episodes of LO-BSI. The highest LO-BSI rate (44%) was among 198 very-low birthweight infants (<1500 g). The most common causative organisms were Coagulase negative staphylococci and Klebsiella (60% and 13%, respectively). The mean hospital stay was 64 days for LO-BSI preterm infants versus 48 days for non-LO BSI preterm infants. Congenital malformations and peripheral catheters were independent risk factors for LO-BSI. Crude mortality rates were 6.9% (LO-BSI) and 3.0% (non-LO-BSI), with an LO-BSI-attributable mortality of 3.9%. CONCLUSION: LO BSI frequently affect very-low-birthweight infants. Strategies to prevent LO-BSI should target peripheral catheters. PMID- 22672071 TI - Ornithine transcarbamylase deficiency: are carrier females suitable donors? PMID- 22672072 TI - Biological rhythms, jetlag and performance in Thoroughbred racehorses. PMID- 22672073 TI - Hide and seek: diagnosing equine viral diseases using molecular biology techniques. PMID- 22672074 TI - Repair or destruction: optimising therapies for joint diseases. PMID- 22672075 TI - On the question of colic: are answers beginning to emerge? PMID- 22672077 TI - Re: The effect of hoof angles on dorsal laminae load of the equine hoof. PMID- 22672079 TI - Re: The effect of hoof angle variations on dorsal lamellar load in the equine hoof. PMID- 22672080 TI - Flii neutralizing antibodies improve wound healing in porcine preclinical studies. AB - Wound healing is an important area of widely unmet medical need, with millions of procedures carried out worldwide which could potentially benefit from a product to improve the wound repair process. Our studies investigating the actin remodeling protein Flightless I (Flii) show it to be an important regulator of wound healing. Flii-deficient mice have enhanced wound healing in comparison to Flii overexpressing mice which have impaired wound healing. For the first time, we show that a Flightless I neutralizing monoclonal antibody (FnAb) therapy is effective in a large animal model of wound repair. Porcine 5 cm incisional and 6.25 cm(2) excisional wounds were treated with FnAb at the time of wounding and for two subsequent days. The wounds were dressed in Tegaderm dressings and left to heal by secondary intention for 7 and 35 days, respectively. At the relevant end points, the wounds were excised and processed for histological analysis. Parameters of wound area, collagen deposition, and scar appearance were analyzed. The results show that treatment with FnAb accelerates reepithelialization and improves the macroscopic appearance of early scars. FnAbs have the potential to enhance wound repair and reduce scar formation. PMID- 22672081 TI - A study comparing insulin lispro mix 25 with glargine plus lispro therapy in patients with Type 2 diabetes who have inadequate glycaemic control on oral anti hyperglycaemic medication: results of the PARADIGM study. AB - AIMS: To test the hypothesis that initiation and intensification with 25% insulin lispro, 75% insulin lispro protamine suspension (LM25), is non-inferior to initiation and intensification with glargine + insulin lispro therapy on change from baseline in HbA(1c). METHODS: In this randomized, non-inferiority (margin of 0.4%), parallel, prospective, multi-country, 48-week, open-label study, patients (n = 426) with Type 2 diabetes inadequately controlled with oral anti hyperglycaemic medications were assigned to either initiating therapy with one daily LM25 injection, progressing up to three daily injections (full analysis set n = 211; per protocol set n = 177) or initiating therapy with one daily glargine injection and progressing up to three daily insulin lispro injections (full analysis set n = 212; per protocol set n = 184). RESULTS: LM25 therapy was found to be non-inferior to glargine + insulin lispro therapy by study end (upper limit of 95% CI < 0.4), with a least-squares mean difference (95% CI) in HbA(1c) (LM25 minus glargine + insulin lispro) of -0.4 mmol/mol (95% CI -2.7 to 1.9); -0.04% (95% CI -0.25 to 0.17). No statistically significant differences between treatment groups were found in the percentage of patients achieving HbA(1c) targets or postprandial blood glucose levels. The increase in insulin dose, number of injections and weight change during the course of the study were similar in both groups. Patients in both groups experienced similar hypoglycaemia rates and safety profile. CONCLUSIONS: For patients with Type 2 diabetes inadequately controlled with oral anti-hyperglycaemic medications, glycaemic control when initiating and intensifying with LM25 therapy was found to be non inferior to treatment with glargine + insulin lispro therapy. PMID- 22672082 TI - Genetic diversity of planktonic eukaryotes in high mountain lakes (Central Pyrenees, Spain). AB - The genetic diversity of planktonic eukaryotic microorganisms (size range 3-40 um) inhabiting 11 alpine lakes of the Central Pyrenees (Spain) was analysed by cloning and sequencing of the 18S rRNA gene. The selected lakes covered a wide range of environmental conditions representative of the regional landscape heterogeneity. Overall, we obtained 953 sequences (averaged length 750 bp) that were grouped in 343 representative OTUs (98% identity). The genetic richness was high, and the 18S rRNA gene sequences spread within nine high-rank taxonomic groups and grouped in 26 eukaryal classes. Most of the sequences affiliated with Stramenopiles (> 55% of total sequences, mostly Chrysophyceae), Cryptophyta and Alveolata (15% each). Three groups had relative abundance < 5%, i.e. Opisthokonta (mostly Fungi), Viridiplantae (mostly Chlorophyceae) and Rhizaria (cercomonads). Finally, minor groups were related to Katablepharidophyta, Euglenozoa and Telonemida. The lakes showed a different community structure being pH, and phosphorous and Chl a concentrations the main environmental drivers. The novelty level was high, and a quarter of the retrieved OTUs were notably divergent (< 97% identity) from any previously known sequence, mainly for Rhizaria and Opisthokonta. More than 50% of the sequences affiliated with clusters exclusively formed by uncultured protists. Cryptophyta and Viridiplantae showed the largest number of sequences closely related to cultured counterparts. This work is the first description of the genetic diversity of eukaryotic assemblages in ultraoligotrophic high mountain lakes, and the study unveils alpine environments as an important reservoir of microbial eukaryotic biodiversity. PMID- 22672083 TI - Normal corneal thickness measurements in pigmented rabbits using spectral-domain anterior segment optical coherence tomography. AB - OBJECTIVE: To document the thickness of the central cornea in pigmented rabbits using spectral-domain anterior segment optical coherence tomography (AS-OCT). ANIMALS STUDIED: Seventeen pigmented rabbits (6 male, 11 female, both eyes) were involved in this study. PROCEDURES: Thirty-four eyes from healthy pigmented rabbits underwent a complete ophthalmologic examination, including AS-OCT. Eight radial scans, 6 mm in length and centered on the cornea, were obtained using the AS-OCT. Corneal thickness was automatically calculated using pachymetry software. Measurements were displayed as the mean and standard deviation for each of the 17 regions defined by the software. The regions were the center (1 mm radius, area a), the inner ring (2.5 mm radius, area b), the outer ring (3 mm radius, area c), and the eight radial scan lines in eight directions (Superior (1), SN (2), Nasal (3), IN (4), Inferior (5), IT (6), Temporal (7), ST (8)) with an angle of 45 degrees between each consecutive scan line (a, b 1-8, c 1-8). RESULTS: There was no statistically significance difference in corneal thickness between gender, eye, and the eight directions (P = 0.804, P > 0.05, P > 0.05). There was a statistical difference between the thickness in areas a, b, and c (P < 0.05). The corneal thickness increased gradually from the center to the periphery of the 6 mm measured. The center corneal thickness was 387 +/- 19.8 MUm for OD and 384 +/- 20.2 MUm for OS. The corneal thicknesses of the thinnest point of the right eyes (OD) and the left eyes (OS) were 376 +/- 20.2 and 370 +/- 16.8 MUm, respectively. There was positive correlation between the thinnest point and area a in both the right eyes (r = 0.892, P < 0.001) and the left eyes (r = 0.832, P < 0.001). CONCLUSIONS: This is the first documentation of the rabbit corneal thickness in vivo using the spectral-domain AS-OCT. Pigmented rabbit corneas were almost 150 MUm thinner than human corneal values. Gender and eye were not associated with any statistical differences in central corneal thickness in this study. PMID- 22672085 TI - Robust changes in expression of brain-derived neurotrophic factor (BDNF) mRNA and protein across the brain do not translate to detectable changes in BDNF levels in CSF or plasma. AB - Adult rats were treated acutely with peripheral kainic acid (KA), and changes in brain-derived neurotrophic factor (BDNF) mRNA and protein were tracked over time across multiple brain regions. Despite robust elevation in both mRNA and protein in multiple brain regions, plasma BDNF was unchanged and cerebrospinal fluid (CSF) BDNF levels remained undetectable. Primary neurons were then treated with KA. BDNF was similarly elevated within neurons, but was undetectable in neuronal media. Thus, while deficits in BDNF signaling have been implicated in a number of diseases, these data suggest that extracellular concentrations of BDNF may not be a facile biomarker for changes in neurons. PMID- 22672084 TI - Regional and voxel-wise comparisons of blood flow measurements between dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) and arterial spin labeling (ASL) in brain tumors. AB - The objective of the current study was to evaluate the regional and voxel-wise correlation between dynamic susceptibility contrast (DSC) and arterial spin labeling (ASL) perfusion magnetic resonance imaging (MRI) measurement of cerebral blood flow (CBF) in patients with brain tumors. Thirty patients with histologically verified brain tumors were evaluated in the current study. DSC-MRI was performed by first using a preload dose of gadolinium contrast, then collecting a dynamic image acquisition during a bolus of contrast, followed by posthoc contrast agent leakage correction. Pseudocontinuous ASL was collected using 30 pairs of tag and control acquisition using a 3-dimensional gradient-echo spin-echo (GRASE) acquisition. All images were registered to a high-resolution anatomical atlas. Average CBF measurements within regions of contrast-enhancement and T2 hyperintensity were evaluated between the two modalities. Additionally, voxel-wise correlation between CBF measurements obtained with DSC and ASL were assessed. Results demonstrated a positive linear correlation between DSC and ASL measurements of CBF when regional average values were compared; however, a statistically significant voxel-wise correlation was only observed in around 30 40% of patients. These results suggest DSC and ASL may provide regionally similar, but spatially different measurements of CBF. PMID- 22672086 TI - Recent advances in pediatric hypertension. PMID- 22672087 TI - The role of uric acid in the pathogenesis of hypertension in the young. AB - Uric acid has been suspected to be a risk factor for hypertension since the 1870s. Numerous epidemiological studies demonstrate an association between uric acid and both incident and prevalent hypertension in diverse populations. Studies in elderly patients have had more variable results, raising the possibility that uric acid may be more significant to hypertension in the young. Animal models support a two-phase mechanism for the development of hyperuricemic hypertension. Initially, uric acid induces vasoconstriction by activation of the renin angiotensin system and reduction of circulating nitric oxide, which can be reversed by lowering uric acid. Over time, uric acid uptake into vascular smooth muscle cells causes cellular proliferation and secondary arteriolosclerosis that impairs pressure natriuresis, causing sodium-sensitive hypertension. Consistent with the animal model data, small clinical trials performed in adolescents with newly diagnosed essential hypertension demonstrate that at least in certain young patients, reduction of serum uric acid can mitigate blood pressure elevation. While more research is clearly necessary, the available data suggest that uric acid is likely causative in some cases of early-onset hypertension. PMID- 22672088 TI - Neurocognitive alterations in hypertensive children and adolescents. AB - Hypertensive adults demonstrate performance deficits on neuropsychological testing compared with scores of normotensive controls. This article reviews emerging preliminary evidence that children with hypertension also manifest neurocognitive differences when compared with normotensive controls. Database and single-center studies suggest that children with hypertension manifest deficits on measures of neurocognition and have an increased prevalence of learning difficulties and that children with hypertension associated with obesity may be at increased risk for depression and anxiety. Studies suggesting blunted cerebrovascular reactivity in children with hypertension are also reviewed. PMID- 22672089 TI - Prehypertension in adolescents: risk and progression. AB - In 2004, the National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents recommended a new designation of prehypertension for children with mildly elevated blood pressure (BP). This description was intended to help identify children most at risk for the development of persistent hypertension for whom targeted prevention programs would be most beneficial and was based largely on expert opinions and epidemiologic normal values. This review summarizes the knowledge that has been gained regarding the epidemiology and risk associated with prehypertension in adolescents since its inception and highlights future challenges in understanding and preventing the development of hypertensive disease in this population. PMID- 22672090 TI - Impact of fetal programming, birth weight, and infant feeding on later hypertension. AB - The concept of developmental origins of adult disease derives from both epidemiologic and basic sciences. This brief review considers the impact of the intrauterine milieu, intrauterine growth retardation, premature birth, and infant feeding on later hypertension and kidney disease. PMID- 22672091 TI - Pediatric ambulatory blood pressure monitoring: indications and interpretations. AB - The prevalence of hypertension in children and adolescents is increasing, especially in obese and ethnic children. The adverse long-term effects of hypertension beginning in youth are known; therefore, it is important to identify young patients who need intervention. Unfortunately, measuring blood pressure (BP) is difficult due to the variety of techniques available and innate biologic variation in BP levels. Ambulatory BP monitoring may overcome some of the challenges clinicians face when attempting to categorize a young patient's BP levels. In this article, the authors review the use of ambulatory BP monitoring in pediatrics, discuss interpretation of ambulatory BP monitoring, and discuss gaps in knowledge in usage of this technique in the management of pediatric hypertension. PMID- 22672092 TI - Update on the pharmacologic treatment of hypertension in pediatrics. AB - J Clin Hypertens (Greenwich). 2012; 14:383-387. (c)2012 Wiley Periodicals, Inc. The past decade of investigation into the pharmacologic treatment of hypertension in children has been rewarding. The studies have shown that blood pressure medications effectively reduce blood pressure in children with hypertension and that these agents are generally well tolerated with few treatment-related adverse effects. While we have advanced our capacity to make rational therapeutic decisions, future efforts must be directed towards comparing the effectiveness of the different classes of antihypertensive agents and studies evaluating the impact of antihypertensive agents on outcome. PMID- 22672093 TI - Antihypertensive drug use by children: are the drugs labeled and indicated? AB - As a result of the Food and Drug Administration (FDA) Modernization Act and the Best Pharmaceuticals for Children Act, the number of medications with FDA approved pediatric labeling has increased. To assess the success of these initiatives, we examined whether antihypertensive drugs used by children with hypertension in 2008 had FDA-approved pediatric labeling and indications. Using a nationwide commercial insurer database, 2915 children with primary (n=2607) and secondary (n=308) hypertension were identified. Drug user rate and days of supply were calculated from pharmacy claims. Drugs were categorized based on pediatric labeling and indication and whether they were recommended for pediatric use. Antihypertensive drugs were used by 889 (34%) children with primary hypertension and 200 children (65%) with secondary hypertension. User rates were 44.3% in hypertensive children younger than 6 years, 30.9% in those 6 years to older than 12 years, and 38.1% in those 12 years to older than 18 years. Seven percent of drugs were neither labeled for pediatric use nor considered recommended for use in children. In children younger than 6 years, 29% of drugs used were not indicated for use in that age group. Despite recent legislative initiatives, many drugs used by hypertensive children still lack pediatric labeling. Additional efforts are needed to close the gap between the availability of drugs that are labeled and indicated for pediatric use and actual drug usage in children. PMID- 22672094 TI - Correlation of blood pressure readings from 6-hour intervals with the daytime period of 24-hour ambulatory blood pressure monitoring in pediatric patients. AB - Shorter-interval (6-hour) ambulatory blood pressure monitoring (ABPM) has been shown to correlate well with 24-hour ABPM in adults, but this has not been studied in children. The authors selected 131 patients aged 9 to 18 who underwent 24-ABPM from 2000-2008. Six-hour intervals beginning at different start times were compared with the daytime and 24-hour period, with subset analysis for normotensive and hypertensive patients. Concordance correlation coefficients (CCCs) were used to assess for agreement. Among normotensive patients, the mean difference between daytime and 6-hour intervals ranged from -0.1 mm Hg to 0.0 mm Hg for diastolic blood pressure (DBP) and -1.1 mm Hg to 0.6 mm Hg for systolic blood pressure (SBP) with CCCs of 0.88 to 0.93 for DBP and 0.93 to 0.96 for SBP. For hypertensive patients, mean difference ranged from -0.6 to 1.3 mm Hg for DBP and -0.8 to 1.1 mm Hg for SBP with CCCs of 0.89 to 0.98 for DBP and 0.86 to 0.95 for SBP. Shorter-interval monitoring correlates significantly with full daytime monitoring in children, allowing for assessment of blood pressure with improved convenience. PMID- 22672095 TI - The present and future of the American Society of Hypertension-2012. PMID- 22672097 TI - The multidisciplinary management of non-melanoma conchal bowl skin cancer. AB - Mohs micrographic surgery (MMS) has been shown to achieve high cure rates and reduce recurrence rates of skin cancer in auricular and preauricular regions. Non melanoma skin cancers of the conchal bowl are difficult to treat due to the challenge of accessing them and their close association with surrounding structures that may be inadvertently involved. Treatment goals in this anatomical area include total tumour removal and maximal tissue conservation to provide the best functional and aesthetic result for the patient. We present two patients with conchal bowl basal cell carcinoma treated with MMS and found to have extensive disease that benefited from collaborative management with an ear, nose and throat (ENT) surgeon. Where extensive subclinical spread is encountered or complex reconstruction is required it is useful to adopt a multidisciplinary approach to achieve total tumour control and maximal tissue conservation. Currently preoperative assessment of tumour margins is difficult and limited data are available on what cases should be co-managed. Our recommendation is that collaborative ENT involvement be reserved for cases where a long history is involved, a history of recurrence, previous failed excisions, close proximity to difficult to access areas, histological subtypes of skin carcinoma that are known to be aggressive or recurrent or when there is suspicion of subclinical spread based on other grounds. PMID- 22672098 TI - Down-regulation of Glucan, Water-Dikinase activity in wheat endosperm increases vegetative biomass and yield. AB - A novel mechanism for increasing vegetative biomass and grain yield has been identified in wheat (Triticum aestivum). RNAi-mediated down-regulation of Glucan, Water-Dikinase (GWD), the primary enzyme required for starch phosphorylation, under the control of an endosperm-specific promoter, resulted in a decrease in starch phosphate content and an increase in grain size. Unexpectedly, consistent increases in vegetative biomass and grain yield were observed in subsequent generations. In lines where GWD expression was decreased, germination rate was slightly reduced. However, significant increases in vegetative growth from the two leaf stage were observed. In glasshouse pot trials, down-regulation of GWD led to a 29% increase in grain yield while in glasshouse tub trials simulating field row spacing and canopy development, GWD down-regulation resulted in a grain yield increase of 26%. The enhanced yield resulted from a combination of increases in seed weight, tiller number, spikelets per head and seed number per spike. In field trials, all vegetative phenotypes were reproduced with the exception of increased tiller number. The expression of the transgene and suppression of endogenous GWD RNA levels were demonstrated to be grain specific. In addition to the direct effects of GWD down-regulation, an increased level of alpha-amylase activity was present in the aleurone layer during grain maturation. These findings provide a potentially important novel mechanism to increase biomass and grain yield in crop improvement programmes. PMID- 22672099 TI - Intraoperative neurophysiologic methods for spinal cord stimulator placement under general anesthesia. AB - OBJECTIVES: To demonstrate that spinal cord stimulators (SCSs) may be placed safely and accurately under general anesthesia (GA) and that the proposed evaluation method activates structures predominantly in the dorsal columns. MATERIALS AND METHODS: Data were retrospectively analyzed from 172 electrodes implanted with spinal cord SCSs at the Lahey Clinic between September 2008 and July 2011. All patients had their SCS placed under GA. Electromyography was recorded from upper or lower limb muscle groups related to the placement of the stimulator electrode. Lateralization was performed based on electromyographic responses and electrode pairs stimulated. In a select group of patients, standard neurophysiologic tests, paired pulse, and collision studies were performed to demonstrate that the pain stimuli were activating the dorsal columns. RESULTS: One hundred fifty-five patients had standard thoracic or cervical SCS placement. Preoperatively this cohort of patients had a visual analog score (VAS) of 7.51 +/ 1.93, while postoperatively the VAS was 3.63 +/- 2.43 (a reduction of 52.11%). Based on the electromyographic recording technique, the electrodes were repositioned intraoperatively in 15.9% of patients. The recovery time (initial approximately 70 msec and complete approximately 150-300 msec) in both the paired pulse tests and the collision studies showed that the stimulation used to elicit the compound muscle action potentials came from antidromic activation of the dorsal columns and not from the corticospinal tract. CONCLUSION: GA SCS is safe and appears to be at least as accurate and efficacious as using the awake SCS placement technique based on a 50% improvement in the VAS. In addition, the technique presented herein demonstrates that the test stimuli activate the same fiber tracts as that of the therapeutic stimulation. PMID- 22672100 TI - Transannular Diels-Alder reactivities of 14-membered macrocylic trienes and their relationship with the conformational preferences of the reactants: a combined quantum chemical and molecular dynamics study. AB - Transannular Diels-Alder (TADA) reactions that occur between the diene and dienophile moieties located on a single macrocyclic triene molecule have been recognized as effective synthetic routes toward realizing complex tricyclic molecules in a single step. In this paper, we report a comprehensive study on the TADA reactions of 14-membered cyclic triene macrocycles to yield A.B.C[6.6.6] tricycles using quantum chemical methods and using classical molecular dynamics simulations. A benchmark study has been performed to examine the reliability of the commonly used ab initio methods and hybrid density functional levels of theory in comparison with results from CCSD(T) calculations to accurately model TADA reactions. The energy barriers obtained using the M06-2X functional were found to be in quantitative agreement with the CCSD(T) level of theory using a reasonably large basis set. Conformational properties of the reactants have been systematically studied using extensive molecular dynamics (MD) simulations. For this purpose, model systems were conceived, and force field parameters corresponding to the dihedral terms in the potential energy function were obtained. Linear relationship between the activation energies corresponding to the TADA reactions and the probability of finding the reactant in certain conformational states was obtained. A clustering method along with optimizations at the molecular mechanics and density functional M06-2X levels has been used to locate the most stable conformation of each of the trienes. PMID- 22672101 TI - The efficacy of manual toothbrushes following a brushing exercise: a systematic review. AB - AIM: To determine the efficacy of manual tooth brushing with respect to toothbrush design and brushing duration. MATERIAL AND METHODS: The PubMed-MEDLINE and Cochrane CENTRAL were searched through October 2010 to identify appropriate studies. The outcome measurement was dental plaque removal following subject brushing. RESULTS: The search yielded 2119 titles and abstracts. Ultimately, 59 papers with 212 brushing exercises as separate legs of the experiments and meeting the eligibility criteria were selected. Overall, a brushing exercise provides a 42% (21) plaque score reduction (95% CI: 41.23; 42.03). Of the brushing studies providing data as assessed according to the Quigley and Hein plaque index, the weighted mean reduction from baseline in plaque scores was 30% (95% CI: 26.79; 33.21). A weighted mean plaque score reduction of 53% (95% CI: 49.51; 56.49) was observed in the experiments using the Navy plaque index. Subanalysis between the different bristle tuft configurations illustrated variation in plaque removal ability (24-61%). The angled bristle design numerically showed the highest mean plaque reduction with either index. A subanalysis of brushing duration revealed after 1 min, a mean reduction of 27% and after 2 min, 41%. CONCLUSION: The efficacy in plaque removal following a brushing exercise is a reduction from baseline plaque scores of 42% on average, with a variation of 30-53% dependent on the plaque index used. The available evidence indicates that bristle tuft arrangement (flat trim, multilevel, angled) and brushing duration are factors that contribute to the variation in observed efficacy. PMID- 22672102 TI - Dietary counselling with or without oral nutritional supplements in the management of malnourished patients: a systematic review and meta-analysis of randomised controlled trials. AB - Dietary counselling and oral nutritional supplements (ONS) are recommended for managing malnutrition. A recent systematic review demonstrated (in separate analyses) that dietary counselling and dietary counselling with ONS improved energy intake, weight and some indices of body composition, although there was considerable heterogeneity. The present analysis aimed to examine the effects on mortality and nutritional indices of dietary counselling given with or without ONS and to explore the heterogeneity in the meta-analyses aiming to characterise the groups most likely to benefit from these interventions. A systematic review and meta-analysis was performed using Cochrane methodology. Twenty-six studies were included in the analysis: 12 comparing dietary counselling with usual care and 14 comparing dietary counselling and ONS if required with usual care (2123 participants). Quality of studies varied. Dietary counselling given with or without ONS had no effect on mortality [relative risk (fixed) = 1.12; 95% confidence interval = 0.86-1.46] but was associated with significant but heterogeneous benefits to weight [mean difference (random) = 1.7 kg; 95% confidence interval = 0.86-2.55], energy intake and some aspects of body composition. Subgroup analyses taking into account clinical background, age, nutritional status, type and length of intervention failed to reveal any differences in mortality, weight change and energy intake between groups. There were insufficient data on functional outcomes to explore these findings. Dietary counselling given with or without ONS is effective at increasing nutritional intake and weight but adequately-powered studies in similar patient populations and standardised for factors that might account for variations in response are required. PMID- 22672103 TI - Coevolutionary genetic variation in the legume-rhizobium transcriptome. AB - Coevolutionary change requires reciprocal selection between interacting species, where the partner genotypes that are favoured in one species depend on the genetic composition of the interacting species. Coevolutionary genetic variation is manifested as genotype * genotype (G * G) interactions for fitness in interspecific interactions. Although quantitative genetic approaches have revealed abundant evidence for G * G interactions in symbioses, the molecular basis of this variation remains unclear. Here we study the molecular basis of G * G interactions in a model legume-rhizobium mutualism using gene expression microarrays. We find that, like quantitative traits such as fitness, variation in the symbiotic transcriptome may be partitioned into additive and interactive genetic components. Our results suggest that plant genetic variation had the largest influence on nodule gene expression and that plant genotype and the plant genotype * rhizobium genotype interaction determine global shifts in rhizobium gene expression that in turn feedback to influence plant fitness benefits. Moreover, the transcriptomic variation we uncover implicates regulatory changes in both species as drivers of symbiotic gene expression variation. Our study is the first to partition genetic variation in a symbiotic transcriptome and illuminates potential molecular routes of coevolutionary change. PMID- 22672104 TI - Etiological agents of superficial mycoses in Kayseri, Turkey. AB - OBJECTIVE: In this study, we aimed to determine the prevalence of agents that cause superficial mycoses and clinical types of superficial mycoses in terms of age and gender in our region were aimed. METHODS: Five hundred samples of nails, skin and skin with hair taken from 476 children and adult patients pre-diagnosed with superficial mycoses were examined by direct microscopy and cultural methods between October 2009 and October 2010. RESULTS: Fungal elements were determined in 212 (42.4%) of the samples by using direct microscopy. Fungal growth was detected in 111 (22.2%) cultures of the same samples. It was found that the most common agents in superficial mycoses were Trichophyton rubrum (43.7%), Candida spp. (28%) and less often, Aspergillus spp., Malassezia spp., Saccharomyces spp., Rhodotorula spp., Trichosporon spp. and Trichophyton verrucosum. CONCLUSION: The significance of diagnosis by using direct microscopy and culturing together was again shown for the diagnosis of superficial fungal infections that follow a chronic course and affect the quality of life of patients. The most common agents in the superficial mycoses were T. rubrum. With this study, defining the aetiological agents of superficial mycoses in the Kayseri region is expected to contribute to the literature in terms of epidemiological data. PMID- 22672105 TI - The effectiveness of intralesional injection of platelet-rich plasma in accelerating the healing of chronic ulcers: an experimental and clinical study. AB - The purpose of this prospective experimental and clinical study is to evaluate the effectiveness of the intralesional injection of platelet-rich plasma (PRP), in the management of non-healing chronic wounds. Skin defects were created in the ears of 20 white New Zealand rabbits. In the study group, autologous PRP was injected intralesionally. The control group was treated conservatively. Nineteen out of 20 cases of the study group healed within a mean time of 24.9 days. In the control group, seven defects healed within a mean period of 26.7 days, seven ulcers did not heal at day 28 and in six cases a full thickness ear defect was recorded. For a 3-year period, 26 patients with chronic ulcers underwent surgical debridement and intralesional injection of PRP. A histological study was performed before and 7 days after PRP injection. Ten patients healed within a mean period of 7 weeks. In 16 cases, PRP prepared the wound bed for the final and simpler reconstructive procedure. Intralesional injection is a newly described method for application of PRP and represents an effective therapeutic option when dealing with non-healing wounds. PMID- 22672106 TI - Analysis of population structure among Korean and Japanese Legionella pneumophila isolates using hsp60 sequences. AB - The population structure of Korean (150 strains) and Japanese (92 strains) Legionella pneumophila isolates along with 18 reference strains were investigated using hsp60 sequence (1647 bp) analysis. Twelve clonal subgroups (hsP-I to hsP-X and hsF-I and hsF-II) were designated on the hsp60 tree, inferred from representative sequences using the neighbor-joining method. Some of the isolates showed unique subgroups depending on the source of isolates, including hsP-I, hsF I, and hsF-II from cooling tower water, and subgroups hsP-VIII and hsP-X from circulating hot water bath. These subgroups may be useful for epidemiological studies to chase or specify sources of infection in Korea and Japan. PMID- 22672107 TI - Effects of cilostazol on cognition and regional cerebral blood flow in patients with Alzheimer's disease and cerebrovascular disease: a pilot study. AB - AIM: It remains unknown whether antiplatelet agents have a preventive effect on cognitive decline in patients with Alzheimer's disease (AD). We investigated the effects of cilostazol, an antiplatelet agent and cyclic adenosine monophosphate phosphodiesterase 3 inhibitor, on cognition and regional cerebral blood flow (rCBF) in elderly patients with AD and cerebrovascular disease (CVD). METHODS: A total of 20 patients with AD and CVD were randomly assigned to a cilostazol group (n=11, 100 mg daily) or control group (n=9, aspirin 100 mg or clopidogrel 50 mg 75 mg daily) for 6 months. RESULTS: The cilostazol group did not show any statistically significant changes in cognitive function test scores, whereas the control group showed statistically significant cognitive decline on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (Japanese version), Revised Wechsler Memory Scale (logical memory-I) and Trail Making Test-A. Analysis of covariance of treatment effect revealed that the cilostazol group showed increased rCBF in the right anterior cingulate lobe compared with baseline, whereas the control group showed decreased rCBF in the left middle temporal gyrus compared with baseline. CONCLUSION: These findings suggest that cilostazol might have a preventive effect on cognitive decline in patients with AD and CVD. PMID- 22672108 TI - Image statistics on the age perception of human skin. AB - BACKGROUND/PURPOSE: Recent research on the age-dependent changes of facial skin has analyzed their correlation with changes in image and colorimetric properties using mainly first- and second-order statistics. The aim of this study is to reveal the importance of third-order statistics and relate those image properties to skin age perception. METHODS: Photographs of the faces of 118 Japanese women ranging in age from 13 to 80 years were taken in a controlled environment. Subsequently, 10 Japanese subjects rated the age perception of skin patches from the cheek area of the original facial images. RESULTS: The age estimation of the skin patches was highly correlated with its chronological age proving that our skin patches contain enough information for age estimation. Also, the perceived age was significantly high correlated to color and lightness statistical values. Specifically, age perception was significantly high correlated with third-order statistics of all channels in CIELAB1976. CONCLUSION: Our results reveal the importance of higher order statistics for the development of nonintrusive skin quality assessments of the skin. PMID- 22672109 TI - Life history trade-offs and evidence for hierarchical resource allocation in two monocarpic perennials. AB - The evolution of floral display is thought to be constrained by trade-offs between the size and number of flowers; however, empirical evidence for the trade off is inconsistent. We examined evidence for trade-offs and hierarchical allocation of resources within and between two populations each of the monocarpic perennials, Cardiocrinum cordatum and C. giganteum. Within all populations, flower size-number trade-offs were evident after accounting for variation in plant size. In addition, variation in flower size explained much variation in flower-level allocation to attraction, and female and male function, a pattern consistent with hierarchical allocation. However, between population differences in flower size (C. cordatum) and number (C. giganteum) were not consistent with size-number trade-offs or hierarchical allocation. The population-level difference in C. cordatum likely reflects the combined influence of a time lag between initiation and maturation of flowers, and higher light levels in one population. Thus, our study highlights one mechanism that may account for the apparent independence of flower size and number in many studies. A prediction of sex allocation theory was also supported. In C. giganteum: plants from one population invested more mass in pistils and less in stamens than did plants from the other population. Detection of floral trade-offs in Cardiocrinum may be facilitated by monocarpic reproduction, production of a single inflorescence and ease of measuring plant size. PMID- 22672110 TI - Auditory spatial deficits following hemispheric lesions: dissociation of explicit and implicit processing. AB - Auditory spatial deficits occur frequently after hemispheric damage; a previous case report suggested that the explicit awareness of sound positions, as in sound localisation, can be impaired while the implicit use of auditory cues for the segregation of sound objects in noisy environments remains preserved. By assessing systematically patients with a first hemispheric lesion, we have shown that (1) explicit and/or implicit use can be disturbed; (2) impaired explicit vs. preserved implicit use dissociations occur rather frequently; and (3) different types of sound localisation deficits can be associated with preserved implicit use. Conceptually, the dissociation between the explicit and implicit use may reflect the dual-stream dichotomy of auditory processing. Our results speak in favour of systematic assessments of auditory spatial functions in clinical settings, especially when adaptation to auditory environment is at stake. Further, systematic studies are needed to link deficits of explicit vs. implicit use to disability in everyday activities, to design appropriate rehabilitation strategies, and to ascertain how far the explicit and implicit use of spatial cues can be retrained following brain damage. PMID- 22672111 TI - Strain echocardiographic assessment of ventricular function after percutaneous pulmonary valve implantation. AB - INTRODUCTION: Percutaneous pulmonary valve implantation (PPVI) is an emerging therapy for pulmonary valve dysfunction. Minimal data on the midterm effects of PPVI on ventricular function exist. We describe the effects of PPVI on right and left ventricular (RV, LV) function with speckle tracking echocardiography. METHODS: Patients who met the inclusion criteria of the Food and Drug Administration Phase 1 Feasibility Clinical Trial PPVI were identified. Patients were studied with echocardiograms at baseline, post-PPVI (day of discharge), 3 months, and at 6 months. Patients were studied by cardiac magnetic resonance at baseline and at 6 months. Longitudinal strain was measured at the basal, mid, and apical portions of the RV, interventricular septum (IVS), and LV. Global RV and LV strain and strain rates were recorded. Paired t-tests were used for analysis. RESULTS: Ten patients were analyzed: nine patients were a variant of tetralogy of Fallot and one patient had complex LV outflow obstruction requiring a Ross and RV pulmonary atresia conduit. Mean age was 24.4 +/- 7.6 years. Indication for PPVI was pulmonary regurgitation in six patients, stenosis in two patients, and stenosis/regurgitation in two patients. After PPVI, both RV systolic pressure and RV to pulmonary artery pressure gradient significantly decreased. Cardiac magnetic resonance RV end-diastolic volume significantly decreased. IVS-mid, IVS apical, and LV-global strain significantly increased and RV-basal decreased immediately after PPVI. Global RV a' strain rate significantly increased immediately after PPVI. However, RV, IVS, and LV strain/strain rate values between baseline and the 6 month echocardiographic study were either similar or significantly decreased. CONCLUSION: Despite improvement in RV hemodynamics, there was a decrease or no improvement in RV and LV function as measured by strain echocardiographic values at midterm follow-up. Larger studies with longer follow-up are needed to determine if these results remain consistent. PMID- 22672112 TI - Factors associated with dry mouth in dependent Japanese elderly. AB - OBJECTIVES: To identify factors associated with dry mouth. BACKGROUND: Dry mouth adversely affects oropharyngeal health, particularly in elderly, and can lead to pneumonia. A better understanding of the epidemiology of dry mouth is therefore important in improving treatment strategies and oral health in high-risk elderly patients. METHODS: We conducted a cross-sectional study involving 383 dependent Japanese elderly individuals (65-84 [n = 167] and >=85 [n = 216] years) at eight long-term care facilities and hospitals. Thirty-four potential factors associated with dry mouth were examined by multiple logistic regression analysis. The primary outcome was dry mouth, as diagnosed by tongue dorsum moisture. RESULTS: We identified that body mass index and severity of physical disability were identified as a potential factors associated with dry mouth in the super-elderly (>=85 years) group, whereas severity of physical disability, outcome measurement time, high daily water consumption, mouth breathing, use of antidepressants and diuretics, and high frequency of daily brushing (>=2 times per day; Odds ratio: 5.56; 95% Confidence Interval: 1.52-20.00) were associated with dry mouth in the 65- to 84-year-old group. CONCLUSION: To our knowledge, this is the first study to identify a link between frequency of daily brushing and dry mouth and suggests that tooth brushing should be encouraged in high-risk dependent Japanese elderly (65-84 years), particularly those taking antidepressants and/or diuretics. PMID- 22672113 TI - Dental laboratory communication regarding removable dental prosthesis design in the UAE. AB - PURPOSE: The purpose of this study was to determine the methods dental practitioners in the United Arab Emirates (UAE) use to communicate cast removable dental prosthesis (RDP) design to dental laboratories; identify common practices taken by dentists/dental technicians prior to fabrication of RDP framework; and seek out dental technicians' attitudes toward their role in RDP design decisions. MATERIALS AND METHODS: All dental laboratories (n = 28) listed in a local telephone directory were invited to complete a questionnaire through a face-to face interview. They were also requested to examine RDP cases fabricated in the past 2 months and identify steps taken by dentists/dental technicians prior to fabrication of the framework. Descriptive statistics were used to report frequencies and percentages. RESULTS: Twenty-one (75%) dental laboratories agreed to participate, out of which 19 had the facilities to fabricate chrome-cobalt RDPs. Cast RDPs comprised approximately 4.04% (+/-2.67) of services provided. A reported 84.2% of dentists frequently communicate through generic lab script, with 89.5% rarely/never giving details regarding RDP design. While 52.6% of labs agree/strongly agree that it is the dentist's responsibility to decide the final RDP design, 94.7% agree/strongly agree that dentists should depend on dental technicians for design-making decisions. A total of 19 RDP cases were reviewed. All 19 were surveyed and designed by dental technicians but received dentist approval of design prior to fabrication. Thirteen (68.4%) had rest-seat preparations done by dentists after approval, and new impressions sent to the lab. No other tooth modifications were noted. CONCLUSION: The responsibility of RDP design appeared to be largely delegated to dental technicians. Importance of tooth modifications seemed to be undervalued and not completed prior to framework fabrication. PMID- 22672114 TI - Corneal refractive surgery: past to present. AB - There have been many historical corneal refractive techniques and procedures developed over the years. From early techniques of radial keratotomy to modern excimer laser techniques, the field of refractive surgery is one of the most rapidly developing in ophthalmology. This review details the historical aspects of the many early techniques up to current techniques used on millions of eyes around the world. PMID- 22672115 TI - Cytokines in human milk and late-onset breast milk jaundice. AB - BACKGROUND: Maternal milk plays an important role in the development of late onset breast milk jaundice (BMJ), possibly due to the unique characteristics of breast milk. The aim of this study was to investigate whether there is a relation between cytokine concentrations in the milk of nursing mothers and BMJ. METHODS: Breast milk samples were collected from breast-feeding mothers of healthy full term neonates, 40 with BMJ and 40 without jaundice. Milk samples were taken between the second and the fourth postpartum week. The concentrations of interleukin (IL)-1 beta, IL-6, IL-8, IL-10, and tumor necrosis factor-alpha were measured by flow cytometric bead array. RESULTS: There were significant differences between the study groups in terms of IL-1 beta concentrations (P= 0.013). Not statistically significant but similar trends were also seen for IL-10 (P= 0.067) and tumor necrosis factor-alpha (P= 0.053) concentrations. However, no significant differences were noted in IL-6 (P= 0.174) and IL-8 (P= 0.285) concentrations. CONCLUSIONS: IL-1 beta concentration seems to be increased in milk of mothers whose infants had BMJ. Although the effect of these cytokines on BMJ is unknown, it may cause prolonged jaundice via hepatic uptake, hepatic excretion, conjugation and intestinal absorption. PMID- 22672116 TI - Incremental cost effectiveness analysis for Haemophilia Home-Based Care Programme in Thailand. PMID- 22672117 TI - Obesity impairs wound closure through a vasculogenic mechanism. AB - Since obesity impairs wound healing and bone marrow (BM)-derived vasculogenic progenitor cells (PCs) are important for tissue repair, we hypothesize that obesity-impaired wound healing is due, in part, to impaired PC mobilization, trafficking, and function. Peripheral blood was obtained from nondiabetic, obese (BMI > 30, n = 25), and nonobese (BMI < 30, n = 17) subjects. Peripheral blood human (h)PCs were isolated, quantified, and functionally assessed. To corroborate the human experiments, 6-mm stented wounds were created on nondiabetic obese mice (TALLYHO/JngJ, n = 15) and nonobese mice (SWR/J, n = 15). Peripheral blood mouse (m)PCs were quantified and wounds were analyzed. There was no difference in the number of baseline circulating hPCs in nondiabetic, obese (hPC-ob), and nonobese (hPC-nl) subjects, but hPC-ob had impaired adhesion (p < 0.05), migration (p < 0.01), and proliferation (p < 0.001). Nondiabetic obese mice had a significant decrease in the number of circulating PCs (mPC-ob) at 7 (p = 0.008) and 14 days (p = 0.003) after wounding. The impaired circulating mPC-ob response correlated with significantly impaired wound closure at days 14 (p < 0.001) and 21 (p < 0.001) as well as significantly fewer new blood vessels in the wounds (p < 0.001). Our results suggest that obesity impairs the BM-derived vasculogenic PC response to peripheral injury and this, in turn, impairs wound closure. PMID- 22672118 TI - Diabetes incidence does not differ between subjects with and without high depressive symptoms--5-year follow-up results of the Heinz Nixdorf Recall Study. AB - AIMS: Cross-sectional studies have consistently reported evidence for an association between diabetes and depressive disorders. However, only limited prospective studies have examined this association, reporting conflicting results. In a population-based cohort study, we compared cumulative incidences of diabetes between participants with and without high depressive symptoms. METHOD: We analysed the 5-year follow-up data from the German Heinz Nixdorf Recall study of 3547 participants without diabetes at baseline [mean age 58.8 (sd 7.6) years, 47.5% male]. Depressive symptoms were defined using the Centre for Epidemiologic Studies Depression scale (cut point >= 17). Diabetes (diagnosed or previously undetected) was identified by self-reported physician-diagnosed diabetes, medication and high blood glucose levels. We estimated 5-year cumulative incidences with 95% confidence intervals and fitted multiple logistic regression models to calculate the odds ratios, adjusted for age, sex, physical activity, smoking, living with or without partner, and educational level. RESULTS: The cumulative incidence of diabetes was 9.2% (95% CI 6.3-12.8) in participants with high depressive symptoms at baseline and 9.0% (95% CI 8.0-10.0) in participants without these symptoms. The age- and sex-adjusted odds ratio of diabetes in participants with depressive symptoms compared with those without was 1.13 [95% CI 0.77-1.68; fully adjusted 1.11 (95% CI 0.74-1.65)]. These results did not substantially change in several additional sensitivity analyses. CONCLUSION: Our study did not show a significantly increased risk of developing diabetes in individuals with high depressive symptoms compared with those without high depressive symptoms during a 5-year follow-up period. PMID- 22672119 TI - An unusual presentation of alveolar echinococcosis in a 12-yr-old immunocompetent child. AB - AE is a parasitic disease caused by Echinococcus multilocularis (E.m.). AE is a rare form of echinococcosis and mostly seen in 50- to 70-yr-old patients. Its asymptomatic invasive tumor-like lesion development period, which lasts as much as 20 yr, is too long. Hence, this disease is very rare in children. Herein, we report an AE in a 12-yr-old girl who was not eligible for surgical treatment because of a radiological evaluation of non-resectable lesion and was scheduled for a LT. PMID- 22672120 TI - Androgen deprivation therapy: past, present and future. AB - Since Huggins and Hodges demonstrated the responsiveness of prostate cancer to androgen deprivation therapy (ADT), androgen-suppressing strategies have formed the cornerstone of management of advanced prostate cancer. Approaches to ADT have included orchidectomy, oestrogens, luteinizing hormone-releasing hormone (LHRH) agonists, anti-androgens and more recently the gonadotrophin-releasing hormone antagonists. The most extensively studied antagonist, degarelix, avoids the testosterone surge and clinical flare associated with LHRH agonists, offering more rapid PSA and testosterone suppression, improved testosterone control and improved PSA progression-free survival compared with agonists. The clinical profile of degarelix appears to make it a particularly suitable therapeutic option for certain subgroups of patients, including those with metastatic disease, high baseline PSA (>20 ng/mL) and highly symptomatic disease. As well as forming the mainstay of treatment for advanced prostate cancer, ADT is increasingly used in earlier disease stages. While data from clinical trials support the use of ADT neoadjuvant/adjuvant to radiotherapy for locally advanced or high-risk localized prostate cancer, it remains to be established whether specific ADT classes/agents provide particular benefits in this clinical setting. PMID- 22672121 TI - Improving the management of patients with prostate cancer receiving long-term androgen deprivation therapy. AB - In many patients with prostate cancer, androgen deprivation therapy (ADT) is administered over prolonged periods of time. The benefits of long-term ADT in patients with advanced disease are well established and, more recently, studies have shown that long-term adjuvant ADT used in combination with radiotherapy improves survival in patients with earlier stages of disease. Nevertheless, clinicians should remain aware of the potential long-term side effects of ADT and the strategies that can be used to manage or prevent long-term complications. One such strategy is intermittent androgen deprivation (IAD), in which patients receive cycles of ADT, the duration of which is usually determined by PSA levels. Accumulating data indicate that this approach improves the tolerability of ADT (particularly sexual dysfunction) and patients' quality of life, without compromising clinical outcomes (progression and survival). Indeed, the latest European Association of Urology guidelines state that IAD should no longer be considered investigational. Nevertheless, some questions remain unanswered, including: who are the most suitable patients for IAD and what are the optimal PSA levels for stopping and restarting treatment? Osteoporosis (and the resultant increased risk of fractures) is a well-recognized complication of long-term ADT. Bone mineral density should be measured before and during long-term ADT and patients advised to make appropriate lifestyle changes to help preserve bone health. Pharmacological intervention is also an option. Denosumab (an NF-kappaB ligand inhibitor) significantly reduces ADT-induced bone loss and the risk of fractures in patients with non-metastatic disease. In those whose disease has metastasized, zoledronate and denosumab are licensed to prevent skeletal-related events and a large randomized study has shown that denosumab is more effective than zoledronate in this setting. PMID- 22672122 TI - New developments in castrate-resistant prostate cancer. AB - Castrate-resistant prostate cancer (CRPC) occurs when disease progresses in the presence of castrate levels of androgens and remains sensitive to further hormonal manipulation. For many years the treatment of CRPC was limited to the use of docetaxel for metastatic disease. However, this has recently changed with the approval of several new agents. Sipuleucel-T, an immunotherapeutic vaccine, is now available in the US for patients with non-metastatic CRPC and abiraterone, an oral enzyme inhibitor of androgen biosynthesis, as well as cabazitaxel, a cytotoxic chemotherapeutic, have been approved for the treatment of metastatic CRPC. Also, denosumab, a subcutaneous antibody, is now an option for the treatment of patients with CRPC with bone metastases, in addition to zoledronic acid, an intravenous bisphosphonate. Further treatment advances for metastatic CRPC therapeutics are in late stage phase III development. These include therapies affecting the androgen receptor (MDV3100) as well as additional immune based therapeutics, PROSTVAC and ipilimumab. A broad range of agents is also emerging under the term targeted therapies. The endothelin-A receptor antagonist zibotentan, the tyrosine kinase inhibitors dasatinib, sorafenib and cabozantinib, the anti-angiogenic agent aflibercept, and the clusterin inhibitor custirsen, are all currently being tested for efficacy in metastatic CRPC. The mechanism of action of these and other promising agents are discussed alongside current therapeutic options and their potential place in the treatment landscape for CRPC is considered. PMID- 22672123 TI - Drivers for change in the management of prostate cancer - guidelines and new treatment techniques. AB - Clinical practice guidelines and new treatment techniques are of particular importance for the effective management of prostate cancer. In Europe, the European Association of Urology guidelines offer a regularly updated evidence based source of recommendations for the optimal treatment of prostate cancer. This review examines recent changes to guidelines highlighting developments in diagnosis, hormonal therapy in advanced and metastatic disease, bone protection, the definition of new terminology such as castrate-resistant prostate cancer, treatment of relapse after hormonal therapy, and cytotoxic therapy for castrate resistant prostate cancer. The review also examines new surgical and radiotherapeutic developments in prostate cancer. This includes minimally invasive techniques such as robot-assisted radical prostatectomy, which is becoming the surgical gold standard for clinically localized disease in many countries. Other promising techniques reviewed include cryosurgical ablation of the prostate, laser-induced interstitial thermotherapy, vascular-targeted photodynamic therapy, and high-intensity focused ultrasound; with the exception of cryotherapy, these approaches are not currently recommended for routine clinical use. Finally, we will review the evidence supporting intensity modulated radiotherapy, an optimized high-precision form of three-dimensional conformal radiotherapy which aims to allow homogeneously increased radiation doses, without increased toxicity to healthy at-risk organs. Novel techniques such as proton beam or carbon ion radiotherapy, which may offer improved and more localized dose distribution with reduced damage to normal tissue, are also examined. PMID- 22672124 TI - Biomarkers intersect with the exposome. AB - The exposome concept promotes use of omic tools for discovering biomarkers of exposure and biomarkers of disease in studies of diseased and healthy populations. A two-stage scheme is presented for profiling omic features in serum to discover molecular biomarkers and then for applying these biomarkers in follow up studies. The initial component, referred to as an exposome-wide-association study (EWAS), employs metabolomics and proteomics to interrogate the serum exposome and, ultimately, to identify, validate and differentiate biomarkers of exposure and biomarkers of disease. Follow-up studies employ knowledge-driven designs to explore disease causality, prevention, diagnosis, prognosis and treatment. PMID- 22672125 TI - Characterization of two genes for the biosynthesis of the labdane diterpene Z abienol in tobacco (Nicotiana tabacum) glandular trichomes. AB - Leaves of tobacco (Nicotiana tabacum) are covered with glandular trichomes that produce sucrose esters and diterpenoids in varying quantities, depending on cultivar type. The bicyclic diterpene Z-abienol is the major labdanoid present in some oriental tobacco cultivars, where it constitutes a precursor of important flavours and aromas. We describe here the identification and characterization of two genes governing the biosynthesis of Z-abienol in N. tabacum. As for other angiosperm labdanoid diterpenes, the biosynthesis of Z-abienol proceeds in two steps. NtCPS2 encodes a class-II terpene synthase that synthesizes 8-hydroxy copalyl diphosphate, and NtABS encodes a kaurene synthase-like (KSL) protein that uses 8-hydroxy-copalyl diphosphate to produce Z-abienol. Phylogenetic analysis indicates that NtABS belongs to a distinct clade of KSL proteins that comprises the recently identified tomato (Solanum habrochaites) santalene and bergamotene synthase. RT-PCR results show that both genes are preferentially expressed in trichomes. Moreover, microscopy of NtCPS2 promoter-GUS fusion transgenics demonstrated a high specificity of expression to trichome glandular cells. Ectopic expression of both genes, but not of either one alone, driven by a trichome-specific promoter in transgenic Nicotiana sylvestris conferred Z-abienol formation to this species, which does not normally produce it. Furthermore, sequence analysis of over 100 tobacco cultivars revealed polymorphisms in NtCPS2 that lead to a prematurely truncated protein in cultivars lacking Z-abienol, thus establishing NtCPS2 as a major gene controlling Z-abienol biosynthesis in tobacco. These results offer new perspectives for tobacco breeding and the metabolic engineering of labdanoid diterpenes, as well as for structure-function relationship studies of terpene synthases. PMID- 22672126 TI - Trends in midwife-attended births in the United States, 1989-2009. AB - INTRODUCTION: Data on attendance at birth by midwives in the United States have been available on the national level since 1989. Rates of certified nurse-midwife (CNM)-attended births more than doubled between 1989 (3.3% of all births) and 2002 (7.7%) and have remained steady since. This article examines trends in midwife-attended births from 1989 to 2009. METHODS: The data in this report are based on records gathered as part of the US National Standard Certificate of Live Birth from a public use Web site, Vital Stats (http://www.cdc.gov/nchs/VitalStats.htm), that allows users to create and download specialized tables. RESULTS: Between 2007 and 2009, the proportion of all births attended by CNMs increased by 4% from 7.3% of all births to 7.6% and a total of 313,516. This represents a decline in total births attended by CNMs from 2008 but a higher proportion of all births because total US births dropped at a faster rate. The proportion of vaginal births attended by CNMs reached an all time high of 11.4% in 2009. There were strong regional patterns to the distribution of CNM-attended births. Births attended by "other midwives" rose to 21,787 or 0.5% of all US births, and the total proportion of all births attended by midwives reached an all-time high of 8.1%. The race/ethnicity of mothers attended by CNMs has shifted over the years. In 1990, CNMs attended a disproportionately high number of births to non-white mothers, whereas in 2009, the profile of CNM births mirrors the national distribution in race/ethnicity. DISCUSSION: Midwife-attended births in the United States are increasing. The geographic patterns in the distribution of midwife-attended births warrant further study. PMID- 22672127 TI - Transcriptome sequencing of wild chickpea as a rich resource for marker development. AB - The transcriptome of cultivated chickpea (Cicer arietinum L.), an important crop legume, has recently been sequenced. Here, we report sequencing of the transcriptome of wild chickpea, C. reticulatum (PI489777), the progenitor of cultivated chickpea, by GS-FLX 454 technology. The optimized assembly of C. reticulatum transcriptome generated 37 265 transcripts in total with an average length of 946 bp. A total of 4072 simple sequence repeats (SSRs) could be identified in these transcript sequences, of which at least 561 SSRs were polymorphic between C. arietinum and C. reticulatum. In addition, a total of 36 446 single-nucleotide polymorphisms (SNPs) were identified after optimization of probability score, quality score, read depth and consensus base ratio. Several of these SSRs and SNPs could be associated with tissue-specific and transcription factor encoding transcripts. A high proportion (92-94%) of polymorphic SSRs and SNPs identified between the two chickpea species were validated successfully. Further, the estimation of synonymous substitution rates of orthologous transcript pairs suggested that the speciation event for divergence of C. arietinum and C. reticulatum may have happened approximately 0.53 million years ago. The results of our study provide a rich resource for exploiting genetic variations in chickpea for breeding programmes. PMID- 22672128 TI - Genome-wide SNP identification in multiple morphotypes of allohexaploid tall fescue (Festuca arundinacea Schreb). AB - BACKGROUND: Single nucleotide polymorphisms (SNPs) provide essential tools for the advancement of research in plant genomics, and the development of SNP resources for many species has been accelerated by the capabilities of second generation sequencing technologies. The current study aimed to develop and use a novel bioinformatic pipeline to generate a comprehensive collection of SNP markers within the agriculturally important pasture grass tall fescue; an outbreeding allopolyploid species displaying three distinct morphotypes: Continental, Mediterranean and rhizomatous. RESULTS: A bioinformatic pipeline was developed that successfully identified SNPs within genotypes from distinct tall fescue morphotypes, following the sequencing of 414 polymerase chain reaction (PCR) - generated amplicons using 454 GS FLX technology. Equivalent amplicon sets were derived from representative genotypes of each morphotype, including six Continental, five Mediterranean and one rhizomatous. A total of 8,584 and 2,292 SNPs were identified with high confidence within the Continental and Mediterranean morphotypes respectively. The success of the bioinformatic approach was demonstrated through validation (at a rate of 70%) of a subset of 141 SNPs using both SNaPshotTM and GoldenGateTM assay chemistries. Furthermore, the quantitative genotyping capability of the GoldenGateTM assay revealed that approximately 30% of the putative SNPs were accessible to co-dominant scoring, despite the hexaploid genome structure. The sub-genome-specific origin of each SNP validated from Continental tall fescue was predicted using a phylogenetic approach based on comparison with orthologous sequences from predicted progenitor species. CONCLUSIONS: Using the appropriate bioinformatic approach, amplicon resequencing based on 454 GS FLX technology is an effective method for the identification of polymorphic SNPs within the genomes of Continental and Mediterranean tall fescue. The GoldenGateTM assay is capable of high-throughput co-dominant SNP allele detection, and minimises the problems associated with SNP genotyping in a polyploid by effectively reducing the complexity to a diploid system. This SNP collection may now be refined and used in applications such as cultivar identification, genetic linkage map construction, genome-wide association studies and genomic selection in tall fescue. The bioinformatic pipeline described here represents an effective general method for SNP discovery within outbreeding allopolyploid species. PMID- 22672129 TI - Technological innovation in spinal cord stimulation: use of a newly developed delivery device for introduction of spinal cord stimulation leads. AB - OBJECTIVE: The use of multiple cylindrical leads and multicolumn and single column paddle leads in spinal cord stimulation offers many advantages over the use of a single cylindrical lead. Despite these advantages, placement of multiple cylindrical leads or a paddle lead requires a more invasive surgical procedure. Thus, the ideal situation for lead delivery would be percutaneous insertion of a paddle lead or multiple cylindrical leads. This study evaluated the feasibility and safety of percutaneous delivery of S-Series paddle leads using a new delivery device called the Epiducer lead delivery system (all St. Jude Medical Neuromodulation Division, Plano, TX, USA). MATERIALS AND METHODS: This uncontrolled, open-label, prospective, two-center study approved by the AZ St. Lucas (Ghent) Ethics Committee evaluated procedural aspects of implantation of an S-Series paddle lead using the Epiducer lead delivery system and any adverse events relating to the device. Efficacy data during the patent's 30-day trial also were collected. RESULTS: Data from 34 patients were collected from two investigational sites. There were no adverse events related to the Epiducer lead delivery system. The device was inserted at an angle of either 20 degrees -30 degrees or 30 degrees -40 degrees and was entered into the epidural space at T12/L1 in most patients. The S-Series paddle lead was advanced four vertebral segments in more than 50% of patients. The average (+/-standard deviation [SD]) time it took to place the Epiducer lead delivery system was 8.7 (+/-5.0) min. The average (+SD) patient-reported pain relief was 78.8% (+24.1%). CONCLUSIONS: This study suggests the safe use of the Epiducer lead delivery system for percutaneous implantation and advancement of the S-Series paddle lead in 34 patients. PMID- 22672130 TI - Effectiveness of a mouthrinse containing active ingredients in addition to chlorhexidine and triclosan compared with chlorhexidine and triclosan rinses on plaque, gingivitis, supragingival calculus and extrinsic staining. AB - OBJECTIVES: To assess the effectiveness of three different mouthrinses- chlorhexidine, triclosan + sodium fluoride and chlorhexidine + triclosan + sodium fluoride + zinc chloride--on plaque, calculus, gingivitis and stains and to evaluate the occurrence of adverse effects with these three treatments. METHODS: Forty-eight healthy subjects participated in a double-blind, randomized, parallel experiment and were randomly allocated to any one of the three experimental mouthrinses: group A (0.2% chlorhexidine (CHX) gluconate), group B (0.03% triclosan + 0.025% sodium fluoride (NaF) + 12% ethyl alcohol) or group C (0.2% CHX + 0.3% triclosan + 0.3% NaF + 0.09% Zn chloride (ZnCl(2)). All the subjects were assessed for gingivitis, plaque, supragingival calculus and extrinsic stains at baseline and at the end of the 21-day experimental period. RESULTS: There was a significant difference (P = 0.046) in the effectiveness for the prevention of gingivitis and plaque, with subjects of group A and group C presenting least and highest gingival and plaque scores, respectively. Significant differences (P = 0.03) were observed for the accumulation of supragingival calculus where the deposition of calculus in group A was nearly double that of the group B, and group B was most effective in the prevention of supragingival calculus. Highest deposition of extrinsic stains was in the group A followed by group C and group B. There was no significant difference between the three treatments for adverse events' occurrence. CONCLUSIONS: CHX mouthrinse was most effective in controlling plaque and gingivitis but caused greatest deposition of extrinsic stains. Supragingival calculus deposition was least in triclosan + NaF group followed by CHX + triclosan + NaF + ZnCl(2) and CHX. More than half of the subjects reported adverse events during the experimental phase. PMID- 22672131 TI - Reconstruction of infected and denuded scrotum and penis by combined application of negative pressure wound therapy and split-thickness skin grafting. AB - Trauma to the genital region and perineum can leave behind lifelong sequelae and pose significant challenges to surgeons in the restoration of functional ability and aesthetic status. Effective methods and techniques are indispensable during the treatment period. Negative pressure wound therapy (NPWT) is a widely accepted technique that is becoming a commonplace treatment in many clinical settings. The purpose of this case report was to introduce the efficacy of the concurrent usage of NPWT and split-thickness skin grafting (STSG) in the reconstruction of genital injuries. A man suffered a traffic accident that caused necrosis of the scrotum and penis associated with a severe infection caused by Pseudomonas aeruginosa and Enterobacter cloacea. After debridement, we adopted NPWT during the postoperative dressing changes and the application of meshed STSG. The outcomes showed that combination of NPWT and split-thickness skin grafts is safe, well-tolerated and efficient in the reconstruction of penoscrotal defects. This could be a versatile tool for reconstruction after perineal and penoscrotal trauma. PMID- 22672132 TI - Serotonin and sleep: breaking the cycle (Commentary on Nakamaru-Ogiso et al.). PMID- 22672133 TI - Differential involvement of the basolateral amygdala and orbitofrontal cortex in the formation of sensory-specific associations in conditioned flavor preference and magazine approach paradigms. AB - Four experiments examined the roles of the basolateral amygdala and orbitofrontal cortex in the formation of sensory-specific associations in conditioned flavor preference and conditioned magazine approach paradigms using unconditioned stimulus (US) devaluation and selective Pavlovian-instrumental transfer procedures in Long Evans rats. Experiment 1 found that pre-training amygdala and orbitofrontal cortex lesions had no detectable effect on the formation or flexible use of sensory-specific flavor-nutrient associations in a US devaluation task, where flavor cues were paired either simultaneously or sequentially with nutrient rewards in water-deprived subjects. In Experiment 2, pre-training amygdala and orbitofrontal cortex lesions both attenuated outcome-specific Pavlovian-instrumental transfer. Experiment 3 indicated that amygdala lesions have no effect on the formation of sensory-specific flavor-nutrient associations in a US devaluation task in food-deprived subjects. Finally, Experiment 4 demonstrated that the outcomes used in Experiment 3 were sufficiently motivationally significant to support conditioned flavor preference. These findings suggest that, although both orbitofrontal cortex and amygdala lesions attenuate the acquisition of sensory-specific associations in magazine approach conditioning, neither lesion reduces the ability to appropriately respond to a flavor cue that was paired with a devalued outcome. PMID- 22672134 TI - Recruitment to intellectual disability research: a qualitative study. AB - BACKGROUND: Difficulties in the recruitment of adults with intellectual disability (ID) to research studies are well described but little studied. The aim of this study was to investigate the difficulties in recruiting to a specific research project, in order to inform future recruitment to ID research. METHODS: Individual semi-structured interviews were held between September 2009 and May 2010 with people who had been involved as intermediaries in recruitment to the research project. These were transcribed verbatim and were independently analysed by two researchers using the Framework approach, who then agreed upon the key emerging themes. RESULTS: Ten interviews were analysed. A number of themes arose, including participant factors (interview anxiety, difficulties in understanding the concept of research, worry about negative feedback), the importance of the researcher (using a personal approach, meeting potential participants prior to recruitment) and motivators [enjoyment of the research interview (participant), obtaining a medical assessment (carer)]. The themes were then used to generate strategies to improve recruitment to ID research: these include the research team applying a more personal approach, developing the recruitment process to allow for multiple meetings with potential participants, and considering motivators for both participants and carers. CONCLUSIONS: This study has used the experiences of intermediaries to identify strategies for improving recruitment to future ID research. This has implications in terms of both time and money. However, successful recruitment is essential to ID research, and we hope that the study will be used by ID researchers to review and improve their recruitment processes. PMID- 22672135 TI - Analysis of serum chemokine levels in patients with HIV-associated eosinophilic folliculitis. AB - BACKGROUND: Patients with human immunodeficiency virus (HIV) infection exhibit various skin diseases. HIV-associated eosinophilic folliculitis (EF) and pruritic papular eruption (PPE) are frequently seen. OBJECTIVE: To understand the mechanisms underlying HIV-associated EF and PPE. METHODS: In order to know frequencies of EF and PPE among patients with HIV infection, we first collected HIV(+) patients who visited dermatology clinic in National Center for Global Health and Medicine during February 2007. We next collected 25 serum samples from HIV(+) patients with skin diseases from May 2008 to May 2010. Eight of 25 patients had EF (EF group), four had PPE (PPE group) and others had non-itchy skin problems such as condyloma acuminatum (no itch group). RESULTS: We first confirmed high frequencies of EF (10.7%) and PPE (5.3%) among 75 HIV(+) patients who visited our clinic during one month. We then measured serum levels of CCL11, CCL17, CCL26 and CCL27. Serum CCL17 levels in EF were significantly higher than those of PPE and no itch group. Serum CCL26 and CCL27 levels in EF were higher than those of no itch group. The number of CD4(+) cells in EF was significantly lower than that in no itch group. CONCLUSION: High serum levels of CCL17, CCL26 and CCL27, and low CD4(+) cell counts may account for the development of HIV associated EF. PMID- 22672136 TI - Analysis of the normative conditions of oral health, depression and serotonin transporter-linked promoter region polymorphisms in an elderly population. AB - AIM: To investigate the association between depression, the normative conditions of oral health and serotonin-transporter-linked promoter region (5-HTTLPR) polymorphisms in a community-dwelling elderly sample. METHODS: Elderly adults living in a community (n=200) were submitted to an oral clinical examination. Depression was assessed using the 15-item Geriatric Depression Scale. The 5 HTTLPR was analyzed by polymerase chain reaction-restriction fragment length polymorphism. Associations between the biomarkers and clinical covariates were assessed by bivariate and multivariate statistical tests. Statistical significance was set at P<0.05. RESULTS: The prevalence of dental caries, periodontal disease, edentulism and oral mucosal lesions was 51.2%, 20.8%, 58.0% and 21.5%, respectively. The prevalence of depression was 21.5%. A higher frequency of the S allele was recorded in older individuals with depression (P=0.017). The present findings showed no significant association between depression and the normative conditions of oral health. The observed allelic polymorphisms were 44% S and 56% L, respectively. Genotypic variants were 33.5% LL, 45.0% SL and 21.5% SS. Individuals carrying the SS genotype showed a significantly high prevalence of periodontal disease (prevalence ratio=3.077, CI 95%=1.008-9.393, P=0.048). CONCLUSION: The present findings suggest that depressive community-dwelling older individuals did not show any association with alterations of oral health normative conditions. However, the SS genotypic polymorphic variant of 5-HTTLPR seems to contribute to the occurrence of periodontal disease in the elderly. PMID- 22672137 TI - Booster effect of canine distemper, canine parvovirus infection and infectious canine hepatitis combination vaccine in domesticated adult dogs. AB - Domesticated adult dogs with antibody titer classified as below 'high' to one or more of canine distemper virus (CDV), canine parvovirus type-2 (CPV-2) and canine adenovirus type-1 (CAdV-1) were then given an additional inoculation, and the effectiveness of this booster evaluated 2 months later. Consequently, CDV and CAdV-1 antibody titer experienced a significant increase, but the same effect was not observed in the antibody titer of CPV-2. These findings suggest that with additional inoculation, a booster effect may be expected in increasing antibody titers for CDV and CAdV-1, but it is unlikely to give an increase in CPV-2 antibody titer. PMID- 22672138 TI - Exercise training, genetics and type 2 diabetes-related phenotypes. AB - Type 2 diabetes mellitus (T2DM) is at virtually pandemic levels world-wide. Diabetes has been referred to as 'a geneticist's nightmare'. However, dramatic advances in our understanding of the genetics of T2DM have occurred in the past 5 years. While endurance exercise training and increased habitual physical activity levels have consistently been shown to improve or be associated with improved T2DM-related phenotypes, there is substantial interindividual variation in these responses. There is some evidence that T2DM-related phenotype responses to exercise training are heritable, indicating that they might have a genetic basis. Genome-wide linkage studies have not identified specific chromosomal loci that could account for these differences, and no genome-wide association studies have been performed relative to T2DM-related phenotype responses to exercise training. From candidate gene studies, there are relatively strong and replicated data supporting a role for the PPARgamma Pro12Ala variant in the interindividual differences in T2DM-related phenotype responses to training. This is a potentially important candidate locus because it affects T2DM susceptibility, has high biological plausibility and is the target for the primary pharmaceutical method for treating T2DM. Is it time to conduct a hypothesis-driven large-scale exercise training intervention trial based on PPARgamma Pro12Ala genotype with T2DM-related phenotypes as the primary outcome measures, while also assessing potential mechanistic changes in skeletal muscle and adipose tissue? Or would it be more appropriate to propose a smaller trial to address the specific skeletal muscle and adipose tissue mechanisms affected by the interaction between the PPARgamma Pro12Ala genotype and exercise training? PMID- 22672139 TI - Study protocol: the Registrar Clinical Encounters in Training (ReCEnT) study. AB - BACKGROUND: Patient encounters are the core learning activity of Australian general practice (family practice) training. Exposure to patient demographics and presentations may vary from one general practice registrar (vocational trainee) to another. This can affect comprehensiveness of training. Currently, there is no mechanism to systematically capture the content of GP registrar consultations. The aim of the Registrar Clinical Encounters in Training (ReCEnT) study is to document longitudinally the nature and associations of consultation-based clinical and educational experiences of general practice registrars. METHODS/DESIGN: This is an ongoing prospective multi-site cohort study of general practice registrars' consultations, entailing paper-based recording of consultation data. The study setting is general practices affiliated with three geographically-based Australian general practice regional training providers. Registrars record details of 60 consecutive consultations. Data collected includes registrar demographics, details of the consultation, patient demographics, reasons for encounter and problems managed. Problems managed are coded with the International Classification of Primary Care (second edition) classification system. Additionally, registrars record educational factors related to the encounter. The study will follow the clinical exposure of each registrar six-monthly over the 18 months to two years (full-time equivalent) of their general practice training program. CONCLUSIONS: The study will provide data on a range of factors (patient, registrar and consultation factors). This data will be used to inform a range of educational decisions as well as being used to answer educational research questions. We plan to use ReCEnT as a formative assessment tool for registrars and help identify and address educational needs. The study will facilitate program evaluation by the participating training providers and thus improve articulation of educational programs with practice experience. From the research point of view it will address an evidence gap - the in-practice clinical and educational experience of general practice trainees, determinants of these experiences, and the determinants of registrars' patterns of practice (for example, prescribing practice) over the course of their training. PMID- 22672140 TI - Heterozygote excess through life history stages in Cestrum miradorense Francey (Solanaceae), an endemic shrub in a fragmented cloud forest habitat. AB - Comparisons of genetic diversity and population genetic structure among different life history stages provide important information on the effect of the different forces and micro-evolutionary processes that mould diversity and genetic structure after fragmentation. Here we assessed genetic diversity and population genetic structure using 32 allozymic loci in adults, seeds, seedlings and juveniles of eight populations of the micro-endemic shrub Cestrum miradorense in a highly fragmented cloud forest in central-eastern Mexico. We expected that due to its long history or rarity, this species may have endured the negative effects of fragmentation and would show moderate to high levels of genetic diversity. High genetic diversity (H(e) = 0.445 +/- 0.03), heterozygote excess (F(IT) = 0.478 +/- 0.034, F(IS) = -0.578 +/- 0.023) and low population differentiation (F(ST) = 0.064 +/- 0.011) were found. Seeds had higher genetic diversity (H(e) = 0.467 +/- 0.05) than the later stages (overall mean for adults, seedlings and juveniles H(e) = 0.438 +/- 0.08). High gene flow was observed despite the fact that the fragmentation process began more than 100 years ago. We conclude that the high genetic diversity was the result of natural selection, which favours heterozygote excess in all stages, coupled with a combination of a reproductive system and seed/pollen dispersal mechanisms that favour gene flow. PMID- 22672141 TI - Utility of intravascular ultrasound guidance in patients undergoing percutaneous coronary intervention for type C lesions. AB - BACKGROUND: Percutaneous coronary intervention (PCI) of complex lesions (i.e., American College of Cardiology/American Heart Association class type C) remains challenging and the outcome may be compromised. The use of intravascular ultrasound (IVUS) to guide PCI was suggested to improve outcome. METHODS: A cohort of 1,984 patients who underwent PCI to type C lesions in our center from April 2000 to March 2010 was identified. Using propensity score matching with clinical and angiographic characteristics, we identified 637 patients who underwent IVUS guidance and 637 patients who had only angiographic guidance PCI. Major adverse cardiovascular events (MACE), a composite end-point of all-cause mortality, Q-wave myocardial infarction and target lesion revascularization, were compared between the 2 groups. RESULTS: After propensity score matching, baseline clinical and angiographic characteristics were well matched. Patients undergoing IVUS-guided PCI had less predilatation and more postdilatation, and were treated more often with cutting balloon. Final diameter stenosis was significantly smaller in the IVUS-guided group (3 +/- 11% vs. 7 +/- 19%, P < 0.001), resulting in higher angiographic success compared with the non-IVUS-guided group (97.9% vs. 94.8%, P < 0.001). The incidence of MACE was significantly lower in the IVUS guided group compared to the angiography-guided group (11.0% vs. 15.6%, P = 0.017) as was cardiac death (1.9% vs. 4.4%, P = 0.010). CONCLUSION: IVUS-guided PCI for complex type C lesions is associated with better outcome and should be considered for these lesions. PMID- 22672142 TI - Enhanced sonophoretic delivery of 5-aminolevulinic acid: preliminary human ex vivo permeation data. AB - BACKGROUND/AIMS: 5-Aminolevulinate (ALA) is an important photodynamic therapy drug for the treatment of actinic keratoses and other non-melanoma skin cancers in cosmetically sensitive areas. One limitation of this drug is a relatively high recurrence rate. Our aim was to evaluate the feasibility of ultrasound augmented ALA delivery in excised human skin. MATERIALS AND METHODS: An ultrasonic delivery device was used to enhance radiolabelled ALA into excised skin. Quantification of ALA was performed after passive and ultrasonic ALA delivery. Transepidermal water loss was used as a measure of barrier function before and after ultrasonic treatment. RESULTS: We found that ultrasonic treatment dramatically increased the mean cumulative amount of ALA to P< 0.0001 from 4 to 8 h when compared to passive ALA treatment. The flux was calculated to be 54.8 +/- 8.0 MUg/cm(2) h with ultrasound treatment. TEWL increased nearly two-fold, from 12.3 to 21.0, after ultrasound treatment. CONCLUSION: Our study supports the use of ultrasound for improved ALA delivery by showing significant improvements in the cumulative drug load and flux via combined ultrasound and ALA treatment. PMID- 22672143 TI - Effects of complete dentures on respiratory performance: spirometric evaluation. AB - OBJECTIVES: There is a lack of data regarding whether edentulous subjects should remove dentures during spirometric measurements or not. The purpose of this study is to determine influences of complete dentures on spirometric parameters in edentulous subjects. MATERIALS AND METHODS: A total of 46 complete denture wearers were included in this study. Respiratory functions of the subjects were evaluated by spirometric tests that were performed in four different oral conditions: without dentures (WOD), with dentures, lower denture only and upper denture only. Forced vital capacity (FVC), peak expiratory flow, forced expiratory volume in 1 s and forced expiratory flow between 25% and 75% were evaluated. The data were analyzed with Friedman, Wilcoxon and paired-samples t tests (alpha = 0.05). RESULTS: Significant differences were found between spirometric parameters in different oral conditions (p < 0.05). In all spirometric parameters, the most important significant differences were found between conditions WOD, FVC and with lower dentures (FVC), and WOD (forced expiratory volume in 1 s) and with upper dentures (forced expiratory volume in 1 s) (p < 0.001). CONCLUSION: It was observed that complete dentures may unfavourably affect spirometric values of edentulous subjects. However, current findings need to be confirmed with advanced respiratory function tests. PMID- 22672144 TI - Influence of implant abutment angulations and two types of fibers on the fracture resistance of ceramage single crowns. AB - PURPOSE: To assess the effect of three implant abutment angulations and two types of fibers on the fracture resistance of overlaying Ceramage single crowns. MATERIALS AND METHODS: Three groups, coded A to C, with different implant abutment angulations (group A/0 degrees , group B/15 degrees , and group C/30 degrees angulation) were restored with 45 overlay composite restorations; 15 Ceramage crowns for each angulation. Groups A, B, and C were further subdivided into three subgroups (n = 5) coded: 1, crowns without fiber reinforcement; 2, crowns with Connect polyethylene reinforcement; and 3, crowns with Interlig glass reinforcement. All crowns were constructed by one technician using the Ceramage System. The definitive restorations (before cementation) were stored in distilled water at mouth temperature (37 degrees C) for 24 hours prior to testing. Before testing, the crowns were cemented using Temp Bond. The compressive load required to break each crown and the mode of failure were recorded. The speed of testing was 1 mm/min. The results were statistically analyzed by two-way ANOVA (p < 0.05). The tested crowns were examined using a stereomicroscope at 40*, and selected crowns (five randomly selected from each group) were further examined by scanning electron microscopy (SEM) to reveal the composite-fiber interface. RESULTS: Fracture resistance of single crowns was not affected (p > 0.05) by the different abutment angulations chosen (0 degrees , 15 degrees , 30 degrees ) or fiber reinforcement (Connect and Interlig fibers). Crowns in group A exhibited average loads to fracture (N) of A1 = 843.57 +/- 168.20, A2 = 1389.20 +/- 193.40, and A3 = 968.00 +/- 387.53, which were not significantly different (p > 0.05) from those of groups B (B1 = 993.20 +/- 327.19, B2 = 1471.00 +/- 311.68, B3 = 1408.40 +/- 295.07), or group C (C1 = 1326.80 +/- 785.30, C2 = 1322.20 +/- 285.33, C3 = 1348.40 +/- 527.21). SEM images of the fractured crowns showed that the origin of the fracture appeared to be located at the occlusal surfaces of the crowns, and the crack propagation tended to extend from the occlusal surface towards the gingival margin. CONCLUSIONS: Implant abutment angulations of 0 degrees , 15 degrees , and 30 degrees did not significantly (p > 0.05) influence the fracture resistance of overlaying Ceramage single crowns constructed with or without reinforcing fibers. The two types of fibers used for reinforcement (Connect and Interlig) had no effect (p > 0.05) on the fracture resistance of overlaying Ceramage single crowns. PMID- 22672145 TI - NorLeu3-A(1-7) stimulation of diabetic foot ulcer healing: results of a randomized, parallel-group, double-blind, placebo-controlled phase 2 clinical trial. AB - This randomized, double-blind, placebo-controlled Phase 2 clinical trial explored NorLeu(3)-A(1-7) (DSC127) safety and healing efficacy in diabetic foot ulcers. Patients with chronic, noninfected, neuropathic, or neuroischemic plantar Wagner Grade 1 or 2 foot ulcers (n = 172) were screened for nonhealing. Subjects were randomized to receive 4 weeks' once-daily topical treatment with 0.03% DSC127 (n = 26), 0.01% DSC127 (n = 27), or Placebo (n = 24), followed by 20 weeks' standard of care. DSC127 was assessed for safety (including laboratory values and adverse events), primary efficacy (% ulcers completely epithelialized at Week 12), and durability of effect. Baseline, demography, and safety parameters were compared between intent-to-treat groups and were comparable. Dose-response curves for DSC127 effect on % area reduction from baseline at Week 12 (40% placebo; 67% 0.01% DSC127; 80% 0.03% DSC127) and 24 (23% placebo; 53% 0.01% DSC127; 95% 0.03% DSC127) followed a log-linear pattern for both intent-to-treat and per-protocol populations. Covariate analysis compared reduction in ulcer area, depth, and volume from baseline; reductions in the 0.03% DSC127 group were greater at Weeks 12 and 24. Placebo-treated ulcers healed in a median 22 weeks vs. 8.5 weeks for 0.03%DSC127 (p = 0.04). This study provides preliminary evidence that DSC127 is safe and effective in accelerating the healing of diabetic foot ulcers. PMID- 22672146 TI - Physical activity promotion and obesity prevention in Girl Scouts: Scouting Nutrition and Activity Program+. AB - BACKGROUND: A previous version of Scouting Nutrition and Activity Program (SNAP) resulted in greater physical activity (PA) during troop meetings, but no impact on girls' body mass index (BMI) or overall PA. The purpose of this study was to evaluate the effects of a 6-month intervention that coupled the evidence-based program SNAP with a channel of communication to parents using health report cards. METHODS: Thirty-two Girl Scouts (mean age = 9.5, SD = 1.4 years) received the SNAP+ intervention. Girls were measured before and after the intervention on body composition, BMI, and 7-day step counts. Troop leaders were trained to implement an interactive obesity-prevention curriculum. Parents received health report cards designed to provide personalized information about their daughters' PA and weight status. RESULTS: The full sample of participants took more steps per day after the intervention (mean difference = 1741, P= 0.007). Results showed that lower values for body fat percentage (P= 0.620), BMI percentile (P= 0.100) and BMI z-scores (P= 0.055) at intervention end were not statistically significant. In the subsample of girls at risk for overweight and obesity, there were lower values for BMI z-score (P= 0.010), BMI percentile (P= 0.027), and body fat percentage (P= 0.053). CONCLUSIONS: From this preliminary study, the SNAP+ intervention appears to be effective for Scout-based promotion of PA, and for the prevention of overweight and obesity in at-risk Girl Scouts, but further evaluation through a fully powered randomized controlled trial is warranted. PMID- 22672147 TI - Allergenic vaccines administration and inhibitor development in haemophilia. PMID- 22672148 TI - Impact of community pharmacy diabetes monitoring and education programme on diabetes management: a randomized controlled study. AB - AIMS: To evaluate the impact of a pharmacist-led patient education and diabetes monitoring programme on HbA(1c) and other cardiovascular risk factors in the community setting. METHODS: Patients with Type 2 diabetes (n = 46) attending two community pharmacies in Hertfordshire, UK were randomized to one of two groups. Patients in the intervention group (n = 23) received a programme of education about diabetes, its treatment and associated cardiovascular risk factors. These patients were seen for monitoring/counselling by a community pharmacist on six occasions over a 12-month period. Measures included HbA(1c), BMI, blood pressure, blood glucose and lipid profile. Patients in the control group (n = 23) underwent these measurements at baseline and at 12 months only, without specific counselling or education over and above usual care. RESULTS: HbA(1c) fell from 66 mmol/mol (8.2%) to 49 mmol/mol (6.6%) (P < 0.001) in intervention group, compared with reduction from 65 mmol/mol (8.1%) to 59 mmol/mol (7.5%) in the control group (P = 0.03). Blood pressure fell from 146/87 to 126/81 mmHg in the intervention group (P = 0.01) compared with no significant change in the control group (136/86 to 139/82 mmHg). Significant reductions in BMI (30.8 to 27 kg/m(2), P < 0.001) and blood glucose (8.8 to 6.9 mmol/l, P < 0.001) were also observed in the intervention group as compared with no significant changes in the control group. Lipid profile changes were mixed. In the intervention group, improvements were seen in diabetes-related quality of life (P = 0.001), diabetes knowledge (P = 0.018), belief about the need for medication (P = 0.004) and reduced concerns regarding medication (P < 0.001). CONCLUSIONS: Education and counselling by community pharmacists can result in favourable improvements to the cardiovascular risk profile of patients with Type 2 diabetes. PMID- 22672149 TI - Follicular carcinoma of thyroid following successful liver transplantation--a report. AB - Follicular carcinoma of the thyroid is a relatively rare malignancy in childhood even in paediatric solid organ transplant recipients. The risk of developing de novo malignancies after liver transplantation is higher compared to the general population. We report an 18-yr-old girl who had successfully undergone liver transplantation five yr earlier for neonatal sclerosing cholangitis complicated by the development of dysplastic nodules. Baseline immunosuppression was with tacrolimus and prednisolone. Mycophenolate mofetil was later added in view of steroid-resistant episodes of graft rejection. She subsequently suffered from marked obesity and essential hypertension needing antihypertensive medication. Five yr after liver transplantation, she presented with a right-sided thyroid swelling that was rapidly progressive with no associated lymphadenopathy and normal systemic examination. Ultrasound of her neck revealed a solid lesion in the right lobe of the thyroid gland with ill-defined margins, and a diagnostic right thyroid lobectomy confirmed the diagnosis of follicular carcinoma with focal capsular and vascular invasion. She underwent total thyroidectomy and currently remains well on thyroxine supplements. Our report highlights the need for high level of suspicion and prompt investigation into any abnormal lesion in the long-term follow-up of solid organ transplant recipients. PMID- 22672150 TI - Atypical features of nanophthalmic macula--a spectral domain OCT study. AB - BACKGROUND: To report atypical features on Spectral domain optical coherence tomography (SD-OCT) in a case of non-familial pure adult nanophthalmos. CASE PRESENTATION: A 39 year old male hyperope was found to have biometric and fundus findings typical of nanophthalmos. The additional atypical features included serous pigment epithelial detachment (PED) in right eye and a cuff of subretinal fluid with underlying yellow deposits along superotemporal arcade in the left eye. Fundus flourescein angiogram showed hyperfluorescence due to window defect, dye pooling due to serous PED in right eye and leak superior to disc in right eye and superotemporally in left eye. Cirrus-SD OCT horizontal line scan passing through the fovea showed extensive inner limiting membrane corrugations causing distorted foveal contour in both eyes. A large juxtafoveal serous PED and a small extrafoval PED were seen with folds in the retinal pigment epithelium (RPE) choriocapillary layer in the right eye. CONCLUSION: Structural disruptions in the RPE-choriocapillary complex in the form of folds or juxtafoveal serous PED and RPE folds can be atypical features of nanophthalmic macula better discerned on high resolution OCT. PMID- 22672151 TI - A national study of adverse effects and global quality of life among candidates for curative treatment for prostate cancer. AB - OBJECTIVES: To provide population-based estimates of typical adverse effects (AEs), e.g. urinary, bowel and sexual dysfunction, in patients with non metastatic recurrence-free prostate cancer (PCa) by curative treatment method, including no treatment. To describe associations between typical AEs and global quality of life (QoL) and to study patients' use of medication for erectile dysfunction (EDmed) and the relationship between such use and global QoL. PATIENTS AND METHODS: In October 2006 a national population-based sample of PCa survivors diagnosed in 2004 was invited to a postal survey focusing on treatment related AEs and global QoL, 12-32 months after treatment start. All had completed their initial treatment. In the present study, 771 compliers were categorized into four groups of localized or locally advanced PCa related to the treatment they completed: (i) no treatment; (ii) radical prostatectomy (RP); (iii) radiotherapy (RAD) without hormones; and (iv) RAD with hormone therapy of 3-24 months duration. Measurement of AEs was restricted to function, using selected items from the 50-item Expanded Prostate Cancer Index Composite and the Brief Sexual Function Inventory among others, whereas global QoL was measured with the 12-item short-form health survey. National prescription data enabled assessment of adjuvant hormone application and EDmed use. RESULTS: Men who had undergone RP reported more urinary incontinence (24%) than the other treatment groups, but had the lowest level of moderate/severe urinary irritative-obstructive symptoms. Men from the 'no treatment' group had the highest level of moderate/severe irritative obstructive urinary symptoms. Men who had undergone RAD reported higher levels of irritative intestinal symptoms and faecal leakage compared with the RP group and the no treatment group. In all treatment groups, poor sexual drive and poor erectile function were common AEs, with men treated with RP reporting the highest prevalence of poor erectile function (89%). Presence of irritative-obstructive urinary symptoms and poor sexual drive were independently associated with low global QoL in multivariate analyses. Fifty percent of the study group had used EDmed after treatment start, but only 47% of them were still using EDmed at the time of the survey. Use of EDmed was not significantly associated with global QoL. CONCLUSIONS: PCa survivors after curative treatment, but also patients without any anticancer therapy, report high levels of urinary and sexual AEs. Irritative-obstructive urinary symptoms and poor sexual drive were significantly associated with low global QoL, whereas erectile function and use of EDmed were not. PMID- 22672152 TI - The sweet and bitter sides of galectins in melanoma progression. AB - Melanoma is the leading cause of skin cancer-related deaths, which is due in large part to its aggressive behavior, resistance to therapy, and ability to metastasize to multiple organs such as the lymph nodes, lung, and brain. Melanoma progresses in a stepwise manner from the benign nevus, to radial spreading through the dermis, to a vertical invasive phase, and finally to metastasis. The carbohydrate-binding family of galectins has a strong influence on each phase of melanoma progression through their effects on immune surveillance, angiogenesis, cell migration, tumor cell adhesion, and the cellular response to chemotherapy. Galectins share significant homology in their carbohydrate recognition domain (CRD), which mediates binding to an array of N-glycosylated proteins located on the surface of tumor cells, endothelial cells, T-cells, and to similarly glycosylated extracellular matrix proteins. Galectins are also present within tumor cells where they perform anti-apoptotic functions and enhance intracellular signaling that results in deregulated expression of genes involved in tumor progression. The most extensively studied galectins, galectin-1 and galectin-3, have been shown to have profound effects on melanoma growth and metastasis by influencing many of these biological processes. PMID- 22672153 TI - Targeted inactivation of transcription factors by overexpression of their truncated forms in plants. AB - Transcription factors are central constituents of gene regulatory networks that control diverse aspects of plant development and environmental adaptability. Therefore they have been explored for decades as primary targets for agricultural biotechnology. A gene of interest can readily be introduced into many crop plants, whereas targeted gene inactivation is practically difficult in many cases. Here, we developed an artificial small interfering peptide (a-siPEP) approach, which is based on overexpression of specific protein domains, and evaluated its application for the targeted inactivation of transcription factors in the dicot model, Arabidopsis, and monocot model, Brachypodium. We designed potential a-siPEPs of two representative MADS box transcription factors, SUPPRESSOR OF OVEREXPRESSOR OF CONSTANS 1 (SOC1) and AGAMOUS (AG), and a MYB transcription factor, LATE ELONGATED HYPOCOTYL (LHY). Transgenic plants overproducing the a-siPEPs displayed phenotypes comparable to those of gene deficient mutants. The a-siPEPs attenuate nuclear import and DNA-binding of target transcription factors. Our data demonstrate that the a-siPEP tool is an efficient genetic means of inactivating specific transcription factors in plants. PMID- 22672154 TI - African immigrant views of HIV service needs: gendered perspectives. AB - This qualitative, community-based research study explored the influence of gender on community perceptions of HIV/AIDS service needs among African immigrant men and women in Calgary, Canada. A total of 41 key informant participants (24 male, 17 female) from 14 sub-Saharan countries completed individual, semi-structured interviews. Thematic interview analysis results produced four themes directly related to HIV and gender, including different sexual standards for men and women, condom use, infidelity, and the need for dialogue between partners on sex and HIV. Each of these themes was related to a contextual theme of "family breakdown", which resulted from cultural adjustment challenges faced by African immigrants. For men, finding suitable employment was a key issue; for women, isolation was identified as an adjustment factor. The findings suggest that a more holistic conception of HIV prevention may be necessary for programmes to be successful and that HIV/AIDS services should be better integrated with newcomer services. PMID- 22672155 TI - Enhanced expression of glutamine synthetase (GS1a) confers altered fibre and wood chemistry in field grown hybrid poplar (Populus tremula X alba) (717-1B4). AB - Hybrid poplar (Populus tremula X P. alba) genetically engineered to express the pine cytosolic glutamine synthetase gene (GS1a) has been previously shown to display desirable field performance characteristics, including enhancements in growth and nitrogen use efficiency. Analysis of wood samples from a 3-year-old field trial of three independently transformed GS1a transgenic hybrid poplar lines revealed that, when compared with wild-type controls, ectopic expression of GS1a resulted in alterations in wood properties and wood chemistry. Included were significant enhancements in wood fibre length, wood density, microfibre angle, per cent syringyl lignin and elevated concentrations of wood sugars, specifically glucose, galactose, mannose and xylose. Total extractive content and acid insoluble lignin were significantly reduced in wood of GS1a transgenics when compared with wild-type trees. Together, these cell wall characteristics resulted in improved wood pulping attributes, including improved lignin solubilization with no concurrent decrease in yield. Trees with increased GS1a expression have improved characteristics for pulp and paper production and hold potential as a feedstock for biofuels production. PMID- 22672156 TI - Escalating therapy of cutaneous side effects of EGFR inhibitors: experience of German reference centers. AB - Recommendations for the management of cutaneous adverse effects of inhibitors of the epidermal growth factor receptor (EGFR) are urgently needed. In this context an expert panel of German dermatologists recently proposed a 3-step management concept based on personal experience and a current literature consensus. While steps 1 and 2 addressed general and preventive measures, as well as the therapy that can be performed by the primary treating physician, here we address the management of challenging cases (step 3) that do not respond well to basic measures and should be referred to an experienced dermatologist. PMID- 22672158 TI - Early semantic and phonological effects on temporal- and muscle-specific motor resonance. AB - Previous studies using functional magnetic resonance imaging and transcranial magnetic stimulation (TMS) explored the relationships between linguistic processing and motor resonance, i.e. the activation of the motor system while perceiving others performing an action. These studies have mainly investigated a specific linguistic domain, i.e. semantics, whereas phonology has been largely neglected. Here we used single-pulse TMS to compare the effects of semantic and phonological processing with motor resonance effects. We applied TMS to the primary motor hand area while subjects observed object-oriented actions and performed semantic and phonological tasks related to the observed action. Motor evoked potentials were recorded in two hand muscles, one of them more involved in the execution of the observed actions than the other one, at three different timepoints (0, 200 and 400 ms after stimulus onset). The results demonstrated increased corticospinal excitability that was muscle-specific (i.e. restricted to the hand muscle involved in the observed action), hemisphere-specific (left), and time-specific (400 ms after stimulus onset). The results suggest an additive effect of independent semantic and phonological processing on motor resonance. The novel phonological effect reported here expands the links between language and the motor system and is consistent with a theory of shared control for hand and mouth. Furthermore, the timing of the semantic effect suggests that motor activation during semantic processing is not an 'epiphenomenon' but rather is essential to the construction of meaning. PMID- 22672157 TI - Cell phones to collect pregnancy data from remote areas in Liberia. AB - PURPOSE: To report findings on knowledge and skill acquisition following a 3-day training session in the use of short message service (SMS) texting with non- and low-literacy traditional midwives. DESIGN: A pre- and post-test study design was used to assess knowledge and skill acquisition with 99 traditional midwives on the use of SMS texting for real-time, remote data collection in rural Liberia, West Africa. METHODS: Paired sample t-tests were conducted to establish if overall mean scores varied significantly from pre-test to immediate post-test. Analysis of variance was used to compare means across groups. The nonparametric McNemar's test was used to determine significant differences between the pre-test and post-test values of each individual step involved in SMS texting. Pearson's chi-square test of independence was used to examine the association between ownership of cell phones within a family and achievement of the seven tasks. FINDINGS: The mean increase in cell phone knowledge scores was 3.67, with a 95% confidence interval ranging from 3.39 to 3.95. Participants with a cell phone in the family did significantly better on three of the seven tasks in the pre-test: "turns cell on without help" (chi(2) (1) = 9.15, p= .003); "identifies cell phone coverage" (chi(2) (1) = 5.37, p= .024); and "identifies cell phone is charged" (chi(2) (1) = 4.40, p= .042). CONCLUSIONS: A 3-day cell phone training session with low- and nonliterate traditional midwives in rural Liberia improved their ability to use mobile technology for SMS texting. CLINICAL RELEVANCE: Mobile technology can improve data collection accessibility and be used for numerous health care and public health issues. Cell phone accessibility holds great promise for collecting health data in low-resource areas of the world. PMID- 22672159 TI - Have medical journals missed the Web 2.0 roller coaster? PMID- 22672160 TI - Improving timeliness while improving the quality of emergency department care. PMID- 22672161 TI - Disaster triage: evidence, consistency and standard practice. PMID- 22672162 TI - Review article: management of cyanide poisoning. AB - Cyanide poisoning is uncommon, but generates interest because of the presumed utility of an antidote immediately available in those areas with a high risk of cyanide exposure. As part of its regular review of guidelines, the Australian Resuscitation Council conducted a systematic review of the human evidence for the use of various proposed cyanide antidotes, and a narrative review of the relevant pharmacological and animal studies. There have been no relevant comparative or placebo-controlled human trials. Nine case series were identified. Treatment with hydroxocobalamin was reported in a total of 361 cases. No serious adverse effects of hydroxocobalamin were reported, and many patients with otherwise presumably fatal poisoning survived. Sodium thiosulphate use was reported in two case series, similarly with no adverse effects. Treatment with a combination of sodium nitrite, amyl nitrite and sodium thiosulphate was reported in 74 patients, with results indistinguishable from those of hydroxocobalamin and sodium thiosulphate. No case series using dicobalt edetate or 4-dimethylaminophenol were identified, but successful use in single cases has been reported. Hydroxocobalamin and sodium thiosulphate differ from alternatives in having negligible adverse effects, and on the basis of current evidence are the antidotes of choice. The indications for the use of an antidote, the requirements for supportive care and a recommended approach for workplaces where there is a risk of cyanide poisoning are presented. PMID- 22672163 TI - Review article: late post-hysterectomy ectopic pregnancy. AB - Ectopic pregnancy after hysterectomy is a rare but potentially life-threatening condition requiring prompt diagnosis to prevent the increased mortality associated with rupture. Twenty-seven cases of late post-hysterectomy ectopic pregnancy reported in the English literature since 1918 were reviewed and analysed for presenting symptoms, missed diagnosis rate at initial presentation, location of ectopic and rupture rate at diagnosis. The presenting symptoms were found to be non-specific. The diagnosis in this population is twice more likely to be missed than in women with intact uteri. The rupture rate is 63%, compared with 37% in women with intact uteri. The majority of late post-hysterectomy ectopic pregnancies (62%) were located in the fallopian tubes. Because of the potential risk of mortality, emergency physicians should always consider the possibility of ectopic pregnancy in childbearing women whose surgical history includes hysterectomy without oophorectomy. Evaluation of abdominal pain in this population should include a pregnancy test to ensure prompt diagnosis when the possibility of pregnancy exists clinically. PMID- 22672164 TI - Organ and tissue donation-related attitudes, education and practices of emergency department clinicians in Australia. AB - OBJECTIVE: The ED is emerging as a priority for efforts to improve rates of organ and tissue donation (OTD) in Australia, but little is known of ED clinicians' attitudes, education or practices in the area. We aimed to determine the attitudes and OTD-related educational background and practices of Australian ED clinicians. METHODS: This was a national cross-sectional survey of members of the Australasian College for Emergency Medicine (ACEM) and the College of Emergency Nursing Australasia (CENA); online questionnaire of 133 items, graded responses using Likert and ordinal multi-category scales, plus open-ended qualitative questions. RESULTS: Of 2969 ACEM members, 599 (20.2%) responded; of 1026 CENA members, 212 (20.7%) responded. Respondents were broadly representative of the membership, with male trainee specialists underrepresented. Most ED staff supported OTD, although many were not certain that facilitating OTD was their role, or that the ED was the right place to identify donors. Around a quarter of medical and nursing staff had received no education regarding OTD. Having received education was related to professional status, cultural background, place of work and years of experience, and was significantly associated with attitude towards OTD and whether staff participated in OTD-related tasks. CONCLUSIONS: More education on OTD is needed and requested by ED clinicians in Australia, particularly on OTD after cardiac death, management of a donor, brain death and obtaining consent. Postgraduate curricula should reflect this need for more OTD related education in emergency medicine and nursing. PMID- 22672165 TI - Effect of working consecutive night shifts on sleep time, prior wakefulness, perceived levels of fatigue and performance on a psychometric test in emergency registrars. AB - OBJECTIVE: To evaluate the effect of working consecutive night shifts on sleep time, prior wakefulness, perceived levels of fatigue and psychomotor performance in a group of Australian emergency registrars. METHODS: A prospective observational study with a repeated within-subjects component was conducted. Sleep time was determined using sleep diaries and activity monitors. Subjective fatigue levels and reciprocal reaction times were evaluated before and after day and night shifts. RESULTS: A total of 11 registrars participated in the study with 120 shifts analysed. Sleep time was found to be similar during consecutive night and day shifts. The mean number of hours spent awake before the end of a night shift was 14.33. Subjective fatigue scores were worst at the end of a night shift. There was no difference in reciprocal reaction time between the end of night shift and the start of day shift. CONCLUSIONS: Registrars sleep a similar amount of time surrounding night and day shifts. Despite reporting the highest levels of fatigue at the end of a night shift, there is no significant difference in reaction times at the end of night shift compared with the beginning of day shift. This correlates with the finding that at the end of night shift the registrars have been awake for less than 16 h, which is the point at which psychomotor performance is expected to decline. PMID- 22672166 TI - How useful are the Heart Foundation risk criteria for assessment of emergency department patients with chest pain? AB - OBJECTIVE: To investigate the prognostic utility of Heart Foundation (Australia) risk stratification table in an ED chest pain population. METHODS: A planned sub study of a prospective observational study of adult patients with potentially cardiac chest pain who underwent evaluation for acute coronary syndrome (ACS) was conducted. Data collected included demographical, clinical, ECG, biomarker and outcome data. Outcome of interest was diagnostic utility of the classification system for ACS or myocardial infarction (MI) at index presentation and major adverse cardiac events (MACE) within 7 and 30 days. MACE included death, cardiac arrest, revascularization, cardiogenic shock, arrhythmia and prevalent (cause of presentation) and incident (occurring within the follow-up period) MI. Analysis was by descriptive and receiver-operator curve analyses. RESULTS: Seven hundred and sixty-eight patients were studied; 109 had MI (14.2%, 95% confidence interval [CI] 11.9-16.8%). There were 88 MACE at 7 days (13.5%, 95% CI 11.1-16.4%) and 93 MACE at 30 days (14.4%%, 95% CI 11.9-17.3%). Diagnostic performance (c-statistic) of the National Heart Foundation risk classification for ACS, MI, 7 and 30 day MACE was 0.74 for each (95% CI 0.71-0.77). Although sensitivity of the high-risk classification for MI, 7 and 30 day MACE was high (99-100%), specificity was low (48-50%). CONCLUSION: The Heart Foundation risk classification shows only fair predictive performance for MI, 7 and 30 day MACE. With specificity of approximately 50%, the recommendation for coronary care admission for all high risk patients is hard to justify. PMID- 22672167 TI - Prevalence and characteristics of patients with risky alcohol consumption presenting to emergency departments in rural Australia. AB - OBJECTIVE: This study measures the prevalence of problematic alcohol consumption in patients of EDs in rural areas of Australia, relative to the general population in the same rural communities. It also identifies the characteristics associated with risky drinking in rural ED patients. METHODS: Surveys containing the Alcohol Use Disorders Identification Test (AUDIT) and questions corresponding to the 2001 Australian Alcohol Guidelines were completed by 1056 patients presenting to five EDs in rural areas of New South Wales, and 756 residents of the same five communities. RESULTS: Relative to the general community, ED patients were statistically significantly more likely to engage in risky alcohol consumption according to the AUDIT (39% vs 20%), alcohol consumption posing a high risk of short-term harm (26% vs 18%) and alcohol consumption posing a high risk of long-term harm (7% vs 3%). Although being aged under 40 years of age, being unmarried, not completing school and being assigned less urgent triage categories were associated with risky alcohol use among ED patients, rates of risky consumption were high across all patient subgroups. CONCLUSIONS: Risky drinking, across a number of measures, is overrepresented in patients of rural Australian EDs relative to the general community, and this type of consumption is not limited to certain subgroups of patients. There is a need for interventions that address both heavy single occasion drinking and excessive regular consumption in patients of rural Australian EDs, with universal interventions recommended rather than targeted programmes. PMID- 22672168 TI - Venous thromboembolism in emergency department patients with rigid immobilization for lower leg injury: Incidence and risk factors. AB - OBJECTIVES: To determine the incidence and risk factors for symptomatic venous thromboembolism (VTE) in adults who are discharged from the ED with rigid immobilization for lower limb injury. METHODS: Eligible patients presenting between 1 December 2008 and 31 December 2010 were identified retrospectively from the Southern Health ED (Monash Medical Centre, Dandenong Hospital, Casey Hospital, all located in Melbourne, Australia) information system. Age, sex, diagnosis, type of splint and other defined potential VTE risk factors were recorded. VTE was confirmed from archived diagnostic imaging or hospital re attendance records. Patients presenting between 1 October 2010 and 31 December 2010 were contacted to detect VTE diagnosed and treated outside of Southern Health. VTE incidence is reported, and comparison of risk factors performed. RESULTS: VTE was initially confirmed in 33 of 1231 patients (2.7%, 95% confidence interval 1.9-3.7). VTE was reported by 3 of 174 in the contacted subgroup (1.7%, 0.4-4.6). Applying this 'missed rate' to the whole sample, the estimated VTE incidence is between 3.1% and 7.1%. Multivariate risk factor analysis found VTE risk to increase with age and a diagnosis of Achilles tendon rupture. CONCLUSION: The estimated VTE incidence was between 3% and 7% in this ED population with age and diagnosis of Achilles tendon rupture increasing risk. Prospective research to more accurately determine incidence, severity and risk stratification is required before firm recommendations on the likely risk versus benefit profile of thromboprophylaxis can be made for this population. PMID- 22672169 TI - Effect on emergency department efficiency of an accelerated diagnostic pathway for the evaluation of chest pain. AB - OBJECTIVE: To compare ED efficiency measures between a trial period using an accelerated diagnostic pathway (ADP) for chest pain evaluation, and a control period using a traditional diagnostic pathway (TDP). METHODS: The TDP used cardiac Troponin I assays at arrival and 6 h. The ADP used point-of-care multimarker (myoglobin, creatine kinase-MB fraction and cardiac Troponin I) assays at arrival and 2 h. Outcomes for consecutive eligible patients included ED length of stay (LOS), discharges and admissions within 4 and 8 h, ED occupancy and cardiac cubicle throughput. RESULTS: There were 413 and 258 eligible patients during the 81 day TDP and 66 day ADP periods. The ED LOS for chest pain patients was reduced in the ADP period for both discharged patients (median 297 [interquartile range {IQR} 230-437]vs 545 [IQR 457-677] min, P < 0.0001) and admitted patients (median 609.5 [IQR 464-857]vs 733.5 [IQR 532-1070] min, P= 0.007). For the whole ED, the percentage of patients discharged or admitted within 4 or 8 h and ED occupancy were similar between periods. Cardiac cubicle throughput increased during the ADP period (217 [95% confidence interval 209.6 224.4]vs 188 [95% confidence interval 174.5-201.8] patients per week, P= 0.005). CONCLUSIONS: The ADP utilizing point-of-care multimarkers led to significantly shorter ED LOS for both discharged and admitted chest pain patients. This was associated with increased cardiac cubicle throughput, but improvements in other whole ED performance indicators were not demonstrated. PMID- 22672170 TI - One hundred tasks an hour: an observational study of emergency department consultant activities. AB - OBJECTIVE: To determine work activity patterns undertaken by ED consultants. METHODS: A single observer time-motion study of consultants rostered to clinical shifts: primarily administrative (Duty) or clinical (Resuscitation). Direct observation of 130 h was undertaken using purpose developed time-stamping software. Primary outcome was task number and time spent in predetermined categories of activity. Comparisons occurred by role delineation, sex, weekday and time of day. RESULTS: For each observed hour consultants performed 101 discrete tasks. A high proportion was spent multitasking; 77 min of overlapping activity in each hour of observation. Consultants spent 42% of each hour on communication, 35% on direct clinical care and 24% on computer use; only 9% was spent on non-clinical tasks. Consultants spent little time (0.6%) accessing e resources. Duty consultants undertook more tasks than Resuscitation consultants, 111 versus 90, and more time was spent on communication (47% vs 35%) and computer use (32% vs 15%) with less on clinical care (29% vs 43%). Female consultants undertook 119 tasks per hour compared with 93 for male consultants; more time was spent on communication (51% vs 38%) and computer use (28% vs 22%). No difference in activity occurred by time of day or weekday. CONCLUSION: ED consultants have very high hourly task rates dominated by communication and clinical activities and frequently multitask. The activity is relatively constant throughout the week but is influenced by sex and role delineation. Appreciation of activity distribution might allow informed interventions to realign the workload or divert tasks to supporting resources. PMID- 22672171 TI - Selection and validation of quality indicators for the Shorter Stays in Emergency Departments National Research Project. AB - OBJECTIVE: Despite the spread of time targets for ED lengths of stay around the world, there have been few studies exploring the effects of such policies on quality of ED care. The Shorter Stays in Emergency Departments (SSED) National Research Project seeks to address this. The purpose of this paper was to describe how the indicators for the SSED study in New Zealand were selected and validated. METHODS: A literature review was used to identify potential indicators. A reference group of 25 key stakeholders from across the health system was convened, with the aims of validating the suggested indicators and to ensure that other candidate indicators were not overlooked. A thematic analysis using a general inductive approach was used to analyse focus group discussions. RESULTS: The major themes were communication, access, timeliness, appropriateness and satisfaction. The 12 indicators selected after literature review were confirmed and two further indicators added after the thematic analysis. The indicators are: hospital and ED length of stay; re-presentation within 48 h; mortality; times to reperfusion, antibiotics, asthma treatment, analgesia, CT for head injury and to theatre (appendicitis and fractured neck of femur); triage time compliance; proportion who left without being seen; quality of discharge information; and ED overcrowding/access block. CONCLUSION: Through literature review and consultation with stakeholders, an evidence-based and clinically relevant set of indicators was compiled with which to measure the effect of the SSED target. This indicator set is consistent with recent international recommendations for measuring quality of care in EDs. PMID- 22672172 TI - Role of head computed tomography in the evaluation of children admitted to the paediatric intensive care unit with new-onset seizure. AB - OBJECTIVE: The role of neuroimaging in children presenting with new-onset seizure is poorly defined. This study evaluates the incidence of abnormal CT findings in children admitted to the paediatric intensive care unit (PICU) with new-onset seizure and examines potential clinical variables associated with abnormal head CT findings. METHODS: A retrospective analysis of 89 previously asymptomatic children admitted to Sydney Children's Hospital (Sydney, Australia) PICU between November 2005 and September 2009 with new-onset seizure was undertaken. Demographic data, clinical details and head CT findings were abstracted from medical records. The clinical significance and the impact of CT findings on acute management decisions was analysed. Clinical variables associated with abnormal clinically significant CT results were examined. RESULTS: A total of 71/89 patients underwent head CT. Of the children who underwent head CT (n= 71), clinically significant CT results were found in 19.7% of patients and head CT findings resulted in a change in acute management in 7% of patients. Children without fever were more than twice as likely to have a positive CT scan (P= 0.049); however, a substantial proportion (6/45) of febrile children also had abnormal scans. Focal seizures were not predictive of abnormal CT results. There was a significant relationship between abnormal CT and multiple seizures (P < 0.02), and age less than 24 months (P < 0.049). CONCLUSION: In this highly selected group head CT findings are frequently abnormal and might change acute management. Children admitted to the PICU with first presentation of seizure who have multiple seizures and/or are aged <2 years should have immediate CT or MRI scanning. PMID- 22672174 TI - Assessment of the effect of Advanced Paediatric Life Support training on level of self-perceived preparedness among health-care workers in Cambodia. AB - OBJECTIVE: The objective of this study was to survey the self-perceived preparedness of Cambodia's Advanced Paediatric Life Support (APLS) providers towards their APLS training and accreditation 5 years post-implementation. METHODS: A cross-sectional survey was administered in December 2009 to APLS providers who had been trained throughout the 5 year period from December 2005 to May 2009. RESULTS: One hundred and two (93%) APLS providers responded. The median rating for their original APLS learning experience was 6 out of 10, and the reported median recall of the APLS teaching content was 7 out of 10. Since their training, 80% had managed a child in cardiac arrest, 85% a child with serious illness and 72% with serious injury. Their subjective preparedness from APLS training for each of the three resuscitation types, on a scale of 1-10, were medians of 7, 7 and 6, respectively. For all groups, perceived preparedness for all three resuscitation types did not differ despite varying lengths of time from their original training. CONCLUSION: APLS training has increased the self perceived preparedness of paediatric health-care workers in Cambodia. RESULTS indicate moderate relevance to real patient resuscitations experienced by health workers, and the perceived recall of the teachings and sense of preparation from APLS training does not significantly decline over time. However, our results suggest subsequent further APLS instructor courses might maintain resuscitation preparedness. PMID- 22672173 TI - Australian triage tags: a prospective, randomised cross-over trial and evaluation of user preference. AB - OBJECTIVE: The aim of this study was to determine if any disaster triage tag is superior to others, based on objective parameters (time, accuracy) and subjective parameters (user preference). A secondary aim was to determine the average time to perform triage assessment using 'sieve and sort'. METHODS: This was a prospective, randomised cross-over trial comparing triage cards currently used, or being implemented, across Australia. De-identified patient information from a trauma database was used to create 125 cases. Volunteer participants were selected from Major Incident Medical Management and Support certified doctors, nurses, paramedics and defence medics and randomised into five groups. Participants completed timed 'sieve and sort' triage exercises on 25 different cases with each of the five triage tags and were then asked to rank the tags in order of preference. Participants also performed timed practical triage assessments (sieve and sort) on two healthy volunteers. RESULTS: Based on the objective measures we did not find that one card was superior to others; however, the Northern Territory card was significantly slower and less accurate (P < 0.001). Doctors were the fastest and most accurate 'sorters' (P < 0.001); however, inaccuracy was the same for all professional groups for the 'sieve'. Participants preferred the SMART card to any other tag. Participants' time to carry out a sieve was approximately 30 s, and 60 s for a sort. CONCLUSION: The SMART card was preferred by participants based on design issues, which supports its implementation. We suggest that doctors are best used in the casualty clearing post. PMID- 22672175 TI - Emergency presentation of emboli to multiple sites from an atrial myxoma. AB - A middle aged man presented to our ED with back pain and confusion, had evidence of acute arterial insufficiency to his lower limbs and myocardial infarction on initial ECG. His workup included an urgent CT, which revealed a filling defect in his dilated left atrium, renal and splenic infarcts, and an embolism in his left internal iliac artery. Urgent embolectomy and fasciotomy could not save his left lower limb, and emergency cardiac surgery was required to excise an atrial myxoma. A brief narrative review of the literature is also presented, with this case being unusual in causing such widespread concurrent multiple organ damage, including stroke and myocardial infarct. PMID- 22672176 TI - Ecstasy-induced acute coronary syndrome: something to rave about. AB - Ecstasy or 3,4-methylenedioxymethamphetamine is a commonly used illicit recreational drug, enjoying popularity for its stimulant effects. Although acute coronary syndrome is recognized after cocaine and methamphetamine use, association with Ecstasy use has rarely been reported. We report three cases of significantly delayed acute coronary syndrome and ST elevation myocardial infarction related to ingestion of Ecstasy. PMID- 22672177 TI - Traumatic appendicitis in minor blunt abdominal injury. AB - Trauma has been reported as a cause of appendicitis on several cases in the literature. The present study reports the relationship between blunt abdominal trauma (BAT) of injury severity score less than 4 and appendicitis. A 17-year-old girl developed appendicitis after a minor BAT. An ecchymosis at the right lower quadrant misled the diagnosis, which was made 1 day later. Laparotomy revealed an inflamed appendix, a few enlarged mesenteric lymph nodes, contusion, as well as punctuated bleeding sites of the caecum. Moreover, based on a brief literature review, the different pathophysiological mechanisms and the difficulties of diagnosis of this entity are discussed. It is suggested that appendicitis should be considered as a possibility in the setting of right lower quadrant pain following minor BAT, when there is clinical suspicion of an inflammatory process within the right iliac fossa. PMID- 22672178 TI - Scapular manipulation for reduction of anterior shoulder dislocation without analgesia: comment. PMID- 22672180 TI - Randomised, controlled trial of immediate total-body computed tomography scanning in trauma patients. PMID- 22672182 TI - Oral HIV-associated Kaposi sarcoma. AB - Kaposi sarcoma (KS), an AIDS defining condition, remains one of the most commonly HIV-associated neoplasms. While the use of highly active antiretroviral therapy (HAART) has brought about a dramatic decrease in the prevalence and incidence of AIDS-KS worldwide, this has not been the case in resource-poor sub-Saharan African countries, where HIV has reached epidemic proportions and human herpesvirus-8 infection is endemic. Oral involvement is a common manifestation of AIDS-associated KS and may be an early presenting finding of HIV infection. The clinical manifestation of oral KS can vary and may have an unpredictable course ranging from mild to fulminant. Rapidly progressive facial lymphoedema associated with extensive advanced oral KS portends a poor prognosis. Oral KS may regress with antiretroviral therapy or may flare up as part of the immune reconstitution inflammatory syndrome. The oral lesions of AIDS-KS are best managed with HAART together with systemic chemotherapy. This article provides a review of contemporary knowledge of the biology, pathology, clinical features and management of oral AIDS-KS. PMID- 22672184 TI - Evaluation of polymerase chain reaction assays for the diagnosis of Trichomonas vaginalis infection in Russia. AB - BACKGROUND: In Russia, the microscopy- and culture-based diagnostics of trichomoniasis is mainly suboptimal. Recent years, domestically produced diagnostic PCR assays have been implemented; however, any evaluation of these PCRs has never been internationally reported. OBJECTIVE: To assess the performance characteristics of PCR assays developed and currently used in Russia to detect Trichomonas vaginalis. MATERIALS AND METHODS: Five PCR assays were assessed on 448 samples (317 vaginal and 131 male urethral) collected from symptomatic attendees of youth centres (n = 415) and patients of a dermatovenereological dispensary that were previously diagnosed with trichomoniasis (n = 33). As reference assay, a sensitive and specific real-time multiplex PCR was used. RESULTS: T. vaginalis DNA was detected in five (all females) of the 415 patients of youth centres (1.2%). All 33 patients previously diagnosed at the venereological dispensary proved to be true positive. For 445 (99.3%) of these 448 samples identical results were obtained by all PCRs, 35 positive and 410 negative. The three discordant samples were positive in all PCRs except one conventional PCR assay. The sensitivities of the PCRs were 94.3-100% and 66.7-100% for vaginal and urethral swabs, respectively. All evaluated assays were 100% specific. The detection limits of the different PCRs ranged from 0.1 to 5 genome equivalents per reaction. CONCLUSION: The PCR assays currently used in Russia for the detection of T. vaginalis have in general high sensitivities and excellent specificities for both vaginal samples and urethral samples from males. PMID- 22672185 TI - Leisure activities among older Germans - a qualitative study. AB - BACKGROUND: Leisure activities contribute to well-being and health in old age. Community nurses should consequently promote such activities among older persons. To do so they need an understanding of older persons' interest in leisure activities. Social contacts, volunteering and pursuit of hobbies and interests constitute the main aspects of leisure. AIMS AND OBJECTIVES: This study aimed to determine the attitudes of older Germans to these aspects to identify user types of leisure time facilities. DESIGN: A qualitative study was conducted within a community-based project in an industrial town in West Germany. METHODS: Data were collected with semi-structured guideline interviews and evaluated with qualitative content analysis according to Mayring. RESULTS: With regard to social contacts attitudes ranged from limited need for contacts to being a reliable member in an older persons' club. Social engagement is only found among the latter. Pursuit of hobbies and interest ranged from being a minimal user of leisure time facilities to refined expectations. Inflexible group structures may prevent potential users from participation despite having a programme in accordance with target group needs. CONCLUSIONS: Attitudes to leisure activities can be described as a combination of two dimensions: the degree of social involvement and the desired refinement of hobbies and interest. IMPLICATIONS FOR PRACTICE: Community nurses who organise social afternoons need to assess these attitudes and should steer social dynamics of in a way that facilitates access for newcomers. PMID- 22672183 TI - Spinal interleukin-10 therapy to treat peripheral neuropathic pain. AB - INTRODUCTION: Current research indicates that chronic peripheral neuropathic pain includes a role for glia and the actions of proinflammatory factors. This review briefly discusses the glial and cytokine responses that occur following peripheral nerve damage in support of utilizing anti-inflammatory cytokine interleukin-10 (IL-10) therapy to suppress chronic peripheral neuropathic pain. SPINAL NONVIRAL INTERLEUKIN-10 GENE THERAPY: IL-10 is one of the most powerful endogenous counter-regulators of proinflammatory cytokine function that acts in the nervous system. Subarachnoid (intrathecal) spinal injection of the gene encoding IL-10 delivered by nonviral vectors has several advantages over virally mediated gene transfer methods and leads to profound pain relief in several animal models. NONVIRAL GENE DELIVERY: Lastly, data are reviewed that nonviral deoxyribonucleic acid (DNA) encapsulated by a biologically safe copolymer, poly(lactic-co-glycolic) acid (PLGA), thought to protect DNA, leads to significantly improved therapeutic gene transfer in animal models, which additionally and significantly extends pain relief. CONCLUSIONS: The impact of these early studies exploring anti-inflammatory genes emphasizes the exceptional therapeutic potential of new biocompatible intrathecal nonviral gene delivery approaches such as PLGA microparticles. Ultimately, ongoing expression of therapeutic genes is a viable option to treat chronic neuropathic pain in the clinic. PMID- 22672186 TI - Sutures versus staples for wound closure in orthopaedic surgery: a randomized controlled trial. AB - BACKGROUND: A recently published meta-analysis comparing metallic staples to sutures in orthopaedic procedures revealed three fold increase in risk for infection in stapled wounds. The studies included in the meta-analysis are at risk of bias due to experimental design limitations. A large randomized controlled trial is proposed to direct orthopaedic surgeons in their choice of wound closure material. METHODS/DESIGN: A parallel group randomized controlled trial with institutional review board approval will be conducted. Patients will be randomized intraoperatively to have skin wounds closed with sutures or staples. Dressings will be used to maintain blinding outcome assessors. The primary outcome measure will be a composite all-cause wound complication outcome measure composed of: infection, wound drainage, wound necrosis, blistering, dehiscence, suture abscess and material sensitivity reaction. An independent review board blinded to treatment assignment will adjudicate suspected complications based on clinical data. All deceased patients will also be reviewed. An interim analysis of complications will take place after half of the patients have been recruited. All data will be analyzed by a blinded statistician. Dichotomous primary and secondary outcome measures will be analyzed using the Chi-squared statistic. Continuous outcome measures will be analyzed using Student's t-test. Subgroup analysis will compare infection rates using sutures versus staples in each anatomic area (upper extremity, pelvis/acetabulum, hip/femur, knee, ankle). A further subgroup analysis will be conducted comparing trauma patients to elective surgery patients. Non-infected revision surgery will also be compared to primary surgery. DISCUSSION: Wound closure material is an afterthought for many orthopaedic surgeons. The combined results of several comparative trials suggests that the choice of wound closure materials may have an impact on the rate of surgical site infections. However, the strength of the evidence is poor given the heterogeneity of the methods employed in previous studies. The following study protocol aims to guide surgeons in their choice of wound closure material by determining if there is a difference in complication rates in sutured and stapled wounds. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov under the identifier NCT01146236 (registered June 14, 2010). PMID- 22672187 TI - Synergistic impact of low serum albumin on intensive care unit admission and high blood urea nitrogen during intensive care unit stay on post-intensive care unit mortality in critically ill elderly patients requiring mechanical ventilation. AB - AIMS: To identify intensive care unit (ICU) risk factors for post-ICU 6-month (PI6M) mortality in critically ill elderly patients requiring mechanical ventilation (MV). METHODS: The present study was a retrospective observational study carried out in a respiratory ICU from December 2008 to December 2009. Medical records of patients aged >=70 years and receiving MV were reviewed. Risk factors of PI6M mortality were assessed by multivariate Cox regression. RESULTS: Of 120 patients enrolled, 46 (38%) died in the PI6M period. As compared with survivors, non-survivors had lower serum albumin levels on ICU admission, lower estimated glomerular filtration rate, higher peak blood urea nitrogen (BUN) levels during ICU stay (ICU-peak BUN), a higher ratio of prolonged steroid use and longer MV length in ICU. Independent risk factors of PI6M mortality were low albumin on admission (hazard ratio [HR] 3.53 per g/dL decrease, 95% CI [1.97 6.33], P<0.001) and high ICU-peak BUN (HR 1.11 per 10-mg/dL increase, [1.04 1.18], P=0.001). The HR for PI6M mortality was 7.88 [2.97-20.91] for patients with both risk factors (albumin <=2.8 g/dL and ICU-peak BUN >72 mg/dL) as compared with those without. For patients with high ICU-peak BUN (>72 mg/dL), PI6M survival was better for those with a reduction in BUN level to <=72 mg/dL at ICU discharge than those without. CONCLUSIONS: Low serum albumin level on ICU admission and high BUN level during ICU stay are two independent risk factors, especially their combination, of PI6M mortality in critically ill elderly patients requiring MV. Furthermore, patients with a reduction in high BUN have a better PI6M survival. PMID- 22672188 TI - The distribution of TPX2 in dividing leaf cells of the fern Asplenium nidus. AB - Plant cell division requires the dynamic organisation of several microtubule arrays. The mechanisms of regulation of the above arrays are under rigorous research. Among several factors that are involved in plant microtubule dynamics, the Targeting Protein for Xklp2 (TPX2) has been found to play a role in spindle organisation, in combination with Aurora kinases, in dividing cells of angiosperms. Microtubule organisation in dividing cells of ferns exhibits certain peculiarities. Accordingly, the presence and distribution of a TPX2 homologue might be helpful in understanding the patterns and regulatory mechanisms of microtubule arrays in this plant group. In this study, a putative TPX2 homologue was identified using Western blotting in the fern Asplenium nidus. It was found, using immunostaining and CLSM, that it is co-localised with perinuclear preprophase microtubules and the prophase spindle, and follows the microtubule pattern during metaphase/anaphase and telophase. During cytokinesis, while in angiosperms TPX2 is degraded, in A. nidus the TPX2 signal persists, co-localising with the phragmoplast. In early post-cytokinetic cells, a TPX2 signal is present on the nuclear surface facing the daughter cell wall and, thereafter it is co localised with the fern-specific microtubule aggregation that lines the new wall, which is possibly involved in cortical microtubule assembly. PMID- 22672189 TI - Lesion classification using 3D skin surface tilt orientation. AB - BACKGROUND/PURPOSE: Current non-invasive diagnostic procedures to detect skin cancer rely on two-dimensional (2D) views of the skin surface. For example, the most commonly-used ABCD features are extracted from the 2D images of skin lesion. However, because the skin surface is an object in three-dimensional (3D) space, valuable additional information can be obtained from a perspective of 3D skin objects. The aim of this work is to discover the new diagnostic features by considering 3D views of skin artefacts. METHODS: A surface tilt orientation parameter was proposed to quantify the skin and the lesion in 3D space. The skin pattern was first extracted from simply captured white light optical clinical (WLC) skin images by high-pass filtering. Then the directions of the projected skin lines were determined by skin pattern analysis. Next the surface tilt orientations of skin and lesion were estimated using the shape from texture technique. Finally the difference of tilt orientation in the lesion and normal skin areas, combined with the ABCD features, was used as a lesion classifier. RESULTS: The proposed method was validated by processing a set of images of malignant melanoma and benign naevi. The scatter plot of classification using the feature of surface tilt orientation alone showed the potential of the new 3D feature, enclosing an area of 0.78 under the ROC curve. The scatter plot of classification, combining the new feature with the ABCD features by use of Principal Component Analysis (PCA), demonstrated an excellent separation of benign and malignant lesions. An ROC plot for this case enclosed an area of 0.85. Compared with the ABCD analysis where the area under the ROC curve was 0.65, it indicated that the surface tilt orientation (3D information) was able to enhance the classification results significantly. CONCLUSIONS: The initial classification results show that the surface tilt orientation has a potential to increase lesion classifier accuracy. Combined with the ABCD features, it is very promising to distinguish malignant melanoma from benign lesions. PMID- 22672190 TI - Simultaneous dual vascular access site for the treatment of coronary artery bifurcation lesions by complex 2-stent technique. AB - OBJECTIVES: To propose an original approach based on simultaneous dual vascular access site (DAS) using 2 small-size guiding catheters to easily perform complex 2-stent techniques for bifurcation coronary lesions (BL). BACKGROUND: Simultaneous kissing stenting and classic crush technique require large 7 or 8Fr guiding catheters leading to large amounts of contrast medium, vascular access site complications, and sometimes frictions or criss-cross of the 2-stent delivery systems. METHODS: DAS was used in 30 patients with BL (11 radio-radial, 16 radio-femoral, and 3 femoro-femoral). Among 60 guiding catheters, the size was 5Fr in 28, 6Fr in 30, and 7Fr in 2 cases of double adjacent BL. When 2 different size catheters were used, contrast medium injections were done using the smallest size catheter. DAS patients were compared with a group of 30 BL patients treated using a single femoral vascular access site (SAS) with 7 or 8Fr catheters. RESULTS: Success rate was 100% in all patients. Contrast volume used was smaller in DAS than in SAS patients (277 +/- 156 cc vs. 380 +/- 165 cc,P = 0.01). No vascular access site complication occurred in the sub-group of the 11 DAS radio radial patients. Postintervention hospitalization duration was shorter in DAS than in SAS (1.9 +/- 2 vs. 2.8 +/- 2 days,P = 0.048). CONCLUSION: DAS allows to successfully perform complex stenting technique of BL using small-size guiding catheters leading to decreased contrast medium volume, decreased vascular access site complications rates, and shortened hospitalization duration. PMID- 22672191 TI - Three-dimensional finite element analysis of custom-made ceramic dowel made using CAD/CAM technology. AB - PURPOSE: This study compares the stress distribution in the structure of a loaded endodontically treated maxillary extracted canine restored with either custom made zirconia (Cercon) or cast gold dowel and core. MATERIALS AND METHODS: Standard treatments were implemented to prepare the gutta-percha-filled root canal and dowel space. The tooth along with the dowel and core fabricated pattern resin were prepared to receive an all-ceramic (Cercon) crown. An impression was made for the tooth preparation with the zirconia milled dowel and core in place to fabricate the Cercon crown using CAD/CAM. The restored canine was scanned, and from the scan two models were constructed with the surrounding ligament and bone. Three-dimensional finite element elastic analysis was then carried out for the stress distribution within the different regions of the two models due to a concentrated force of 100 N applied at the mid-lingual area. Analyses were made for three load angulations, vertical, buccolingual horizontal, and an in-between oblique force at 45(o) . Each region of the models was assumed isotropic and homogeneous. The two restored canines with zirconia and gold were compared in terms of the resulting maximum tensile, compressive, and Von Mises stresses. RESULTS: Generally, there were no significant differences in the maximum stresses in most regions for both models. Von Mises stresses for zirconia dowel and core was 8.966 MPa and for cast gold dowel and core was 8.752 MPa. The maximum tensile stress for zirconia dowel and core was 9.326 MPa, and for cast gold dowel and core was 8.166 MPa. CONCLUSIONS: The present work validates the use of CAD/CAM zirconia material for ceramic dowel and cores. CLINICAL IMPLICATIONS: CAD/CAM Zirconia can be used for a custom-made dowel and core in an esthetically demanding zone as an esthetic replacement for a metal cast dowel and core when restoring endodontically treated teeth. PMID- 22672192 TI - Widespread uncoupling between transcriptome and translatome variations after a stimulus in mammalian cells. AB - BACKGROUND: The classical view on eukaryotic gene expression proposes the scheme of a forward flow for which fluctuations in mRNA levels upon a stimulus contribute to determine variations in mRNA availability for translation. Here we address this issue by simultaneously profiling with microarrays the total mRNAs (the transcriptome) and the polysome-associated mRNAs (the translatome) after EGF treatment of human cells, and extending the analysis to other 19 different transcriptome/translatome comparisons in mammalian cells following different stimuli or undergoing cell programs. RESULTS: Triggering of the EGF pathway results in an early induction of transcriptome and translatome changes, but 90% of the significant variation is limited to the translatome and the degree of concordant changes is less than 5%. The survey of other 19 different transcriptome/translatome comparisons shows that extensive uncoupling is a general rule, in terms of both RNA movements and inferred cell activities, with a strong tendency of translation-related genes to be controlled purely at the translational level. By different statistical approaches, we finally provide evidence of the lack of dependence between changes at the transcriptome and translatome levels. CONCLUSIONS: We propose a model of diffused independency between variation in transcript abundances and variation in their engagement on polysomes, which implies the existence of specific mechanisms to couple these two ways of regulating gene expression. PMID- 22672193 TI - Quality standards for child and adolescent mental health in primary care. AB - BACKGROUND: Child and adolescent mental health problems are common in primary healthcare settings. However, few parents of children with mental health problems express concerns about these problems during consultations. Based on parental views, we aimed to create quality of care measures for child and adolescent mental health in primary care and develop consensus about the importance of these quality standards within primary care. METHODS: Quality Standards were developed using an iterative approach involving four phases: 1) 34 parents with concerns about their child's emotional health or behaviour were recruited from a range of community settings including primary care practices to participate in focus group discussions, followed by validation groups or interviews. 2) Preliminary Quality Standards were generated that fully represented the parents' experiences and were refined following feedback from an expert parent nominal group. 3) 55 experts, including parents and representatives from voluntary organisations, across five panels participated in a modified two-stage Delphi study to develop consensus on the importance of the Quality Standards. The panels comprised general practitioners, other community-based professionals, child and adolescent psychiatrists, other child and adolescent mental health professionals and public health and policy specialists. 4) The final set of Quality Standards was piloted with 52 parents in primary care. RESULTS: In the Delphi process, all five panels agreed that 10 of 31 Quality Standards were important. Although four panels rated 25-27 statements as important, the general practitioner panel rated 12 as important. The final 10 Quality Standards reflected healthcare domains involving access, confidentiality for young people, practitioner knowledge, communication, continuity of care, and referral to other services. Parents in primary care agreed that all 10 statements were important. CONCLUSIONS: It is feasible to develop a set of Quality Standards to assess mental healthcare provision for children and adolescents seen within primary healthcare services. Primary care practitioners should be aware of parental perspectives about quality of care as these may influence help-seeking behaviours. PMID- 22672194 TI - SAP and XIAP deficiency in hemophagocytic lymphohistiocytosis. AB - Hemophagocytic lymphohistiocytosis (HLH) is a multisystem inflammatory disorder due to cytokine overproduction from excessively activated lymphocytes and macrophages. HLH has been divided into two subgroups: primary HLH and secondary HLH. Primary HLH includes PRF1, UNC13D, STX11, STXBP2, RAB27A, LYST, SH2D1A and XIAP gene mutations; and secondary HLH is associated with infections, malignancies and autoimmune diseases. Among primary HLH-related genes, SH2D1A and XIAP are genetically responsible for X-linked lymphoproliferative syndrome (XLP) due to signaling-lymphocytic-activation-molecule-associated protein (SAP) and XIAP deficiencies, respectively. XLP is characterized by extreme vulnerability to Epstein-Barr virus infection. The major clinical manifestations of XLP consist of HLH (60%), lymphoproliferative disorder (30%) and dysgammaglobulinemia (30%). Analysis of clinical phenotypes of XLP patients suggests that XLP predominantly shows familial HLH phenotypes, whereas some XLP patients present sporadic HLH. For many decades, clinicians and investigators have been concerned with possible XLP in young boys presenting with Epstein-Barr-virus-associated HLH. This review aims to describe the new knowledge about XLP and to draw the attention of the pediatrician to XLP, which should be differentiated from other forms of HLH. PMID- 22672195 TI - Outcome of phacoemulsification in patients with and without Pseudoexfoliation syndrome in Kashmir. AB - BACKGROUND: The aim of the study is to compare the outcome of phacoemulsification in patients with and without pseudoexfoliation syndrome in Kashmir. METHODS: 200 patients were prospectively evaluated and divided into 2 groups. Group 1 comprised 100 cases with pseudoexfoliation and Group 2 (control) 100 cases without pseudoexfoliation. Phacoemulsification with posterior chamber intraocular lens implantation was performed by 3 surgeons. Intraoperative and postoperative observations were made in both the groups at regular intervals upto 6 months. A chi square test was used for statistical analysis. RESULTS: Patients with pseudoexfoliation were significantly older (P = 0.000), had harder cataract(P = 0.030) and smaller mean pupil diameter(P = 0.000) than the control group. Intraoperative complications were comparable between the 2 groups except the occurrence of zonular dehiscence which was seen in 7% patients of Group 1 compared to 0% in Group 2. Higher postoperative inflammatory response was seen in Group 1(P = 0.000). Decrease in intraocular pressure (IOP) at all postoperative measurements was more in Group 1(P = 0.000). The visual acuity was better in the control group in the early postoperative period (P = 0.029), however the final visual acuity at 6 months was comparable between the 2 groups. CONCLUSIONS: Phacoemulsification in presence of pseudoexfoliation necessitates appropriate surgical technique to avoid intraoperative complications. Pseudoexfoliation is associated with higher inflammatory response, significant postoperative IOP drop and satisfactory visual outcome. PMID- 22672196 TI - Controversies in performing a randomized control trial and a systemic review. PMID- 22672197 TI - Development of associations among central adiposity, adiponectin and insulin sensitivity from adolescence to young adulthood. AB - OBJECTIVE: To examine associations of central adiposity, serum adiponectin and clamp-derived insulin sensitivity in a single longitudinal cohort from early adolescence to young adulthood. METHODS: The cohort was examined three times at mean ages 15 years (n = 308), 19 years (n = 218) and 22 years (n = 163). Insulin sensitivity was measured with the euglycaemic hyperinsulinaemic clamp. Circulating adiponectin was measured by enzyme-linked immunosorbent assay. Computed tomography scans were used at mean age 22 to compute subcutaneous and visceral abdominal fat volume. Partial Pearson correlations and linear regression were used to examine cross-sectional associations at each examination. RESULTS: The moderate negative correlation between waist circumference and adiponectin was significant and essentially unchanged from mean age 15 (-0.32, P < 0.0001) to mean age 22 (-0.29, P < 0.002), whereas the negative correlation between waist circumference and insulin sensitivity and the positive correlation between adiponectin and insulin sensitivity increased steadily in magnitude to mean age 22 (-0.29, P = 0.0002; and 0.32, P < 0.0001, respectively). In regression models including both visceral and subcutaneous fat, only visceral fat was significantly associated with insulin sensitivity, while only subcutaneous fat was nearly significantly associated with adiponectin. CONCLUSIONS: This study shows that the significant negative relationship between waist circumference and adiponectin predated the development of significant relationships between insulin sensitivity and both waist circumference and adiponectin. It also shows that adiponectin is more closely related to subcutaneous fat and insulin sensitivity is more closely related to visceral fat in young adults. PMID- 22672198 TI - Successful in vitro fertilization and pregnancy in Glanzmann thrombasthenia. PMID- 22672199 TI - High-intensity focused ultrasound (HIFU) for definitive treatment of prostate cancer. AB - What's known on the subject? and What does the study add? Novel therapeutic methods have emerged in recent years as 'focal' treatment alternatives in which cancer foci can be eradicated and greatly reducing the associated side-effects of radical treatment. High-intensity focused ultrasound (HIFU) seems to result in a well fitted technology, which has proven short- to medium-term cancer control, with a low rate of complications comparable with those of established therapies. This is an up-to-date review of the available literature on HIFU as a definitive treatment of prostate cancer. It describes the technique in a comprehensive approach in terms of technical features, procedure, indications, and gives an overview of its historical background; finally, we present the future applications of HIFU and its development trend. OBJECTIVES: * To provide an up-to date review of the available literature on high-intensity focused ultrasound (HIFU) as a definitive treatment of prostate cancer. * To present the technique in a comprehensive approach, comparing the available devices according to the existing evidence in terms of technical features, procedure, indications, and to give an overview of its historical background; and finally, to discuss future applications of HIFU and its development trend. MATERIALS AND METHODS: * A systematic literature search was conducted using MEDLINE and EMBASE via Ovid databases (January 2000 to December 2011), to identify studies on HIFU for treatment of prostate cancer. * Only English-language and human-based full manuscripts that reported on case series studies with >50 participants, patient characteristics, efficacy and safety data were included. RESULTS: * No randomised controlled trials were identified by the literature search. We identified 31 uncontrolled studies that examined the efficacy of HIFU as primary treatment and two studies that examined the efficacy of HIFU as salvage treatment. * Most treated patients had localised prostate cancer (stage T1-T2); Gleason scores of 2 10 and mean prostate specific antigen (PSA) values of 4.6-12.7 ng/mL. The mean age range of the patients was 64.1-72 years. The mean follow-up ranged from 6.4 to 76.8 months. Negative biopsy rates ranged from 35 to 95%. PSA nadirs ranged from 0.04 to 1.8 ng/mL. The 5-year disease-free survival rates ranged from 61.2 to 95%; 7- and 8-year disease free survival rates ranged from 69 to 84%. * The most common complications associated with the HIFU procedure as the primary treatment included: urinary retention (<1-20%); urinary tract infections (1.8 47.9%); stress or urinary incontinence (<1-34.3%); and erectile dysfunction (20 81.6%). * Recto-urethral fistula was reported in <2% of patients. * Treatment related morbidity appeared to be reduced by the combination of transurethral resection (TURP) of the prostate and HIFU. CONCLUSIONS: * Novel therapeutic methods have emerged in recent years as 'focal' treatment alternatives, in which cancer foci could be eradicated by greatly reducing the associated side-effects of radical treatment. * HIFU seems to result in short- to medium-term cancer control, with a low rate of complications comparable with those of established therapies. * However, longer-term follow-up studies are needed to evaluate cancer specific and overall survival. If available promising results on HIFU for definitive treatment of prostate cancer are confirmed in future prospective trials, focal therapy could start to challenge the current standard of care. PMID- 22672200 TI - Neurocognitive deficits in HIV-infected women and victims of childhood trauma. AB - The study investigated the behavioral and brain effects of childhood trauma and human immunodeficiency virus (HIV) infection, both separately and in combination, and assessed potential interactions in women who were dually affected. Eighty three HIV-positive and 47 matched HIV-negative South African women underwent neuromedical, neuropsychiatric, and neurocognitive assessments. Univariate tests of significance assessed if either HIV infection or childhood trauma, or the combination, had a significant effect on neurocognitive performance. The majority of women were Black (96%) and had an average age of 30 years. An analysis of covariance revealed significant HIV effects for the Hopkins Verbal Learning Test (HVLT) learning and delay trials (p < 0.01) and the Halstead Category Test (HCT) (p < 0.05). A significant trauma effect was seen on the HVLT delay trial (p < 0.05). The results provide evidence for neurocognitive dysfunction in memory and executive functions in HIV-infected women and memory disturbances in trauma exposed women. PMID- 22672201 TI - Pre-transplant myeloid dendritic cell deficiency associated with cytomegalovirus infection and death after kidney transplantation. AB - BACKGROUND: Dendritic cells (DCs) are potent antigen-presenting cells critical for immunity. We previously demonstrated a significant association between pre transplant blood myeloid dendritic cell (mDC) and plasmacytoid dendritic cell (pDC) deficiency and post-transplant BK viremia in renal transplant recipients. In the current post-hoc analysis, we studied the association of these same pre transplant DC levels with other post-transplant outcomes. METHODS: Pre-transplant peripheral blood mDC and pDC levels were quantified using flow cytometry in 78 patients undergoing kidney transplantation. Post-transplant outcomes were analyzed, including infection, rejection, and patient death, with a median follow up of 5.3 years. Associations between DC levels and outcomes were assessed using logistic regression analysis and Cox proportional hazards models. RESULTS: An independent association of mDC levels with post-transplant cytomegalovirus infection (adjusted odds ratio 7.0, P = 0.01) and patient death (adjusted hazard ratio 13.0, P = 0.015) was found. No associations were demonstrated between levels of either DC subtype and bacterial infections or rejection. CONCLUSIONS: Pre-transplant mDC deficiency is significantly associated with CMV infection and death after kidney transplantation. PMID- 22672202 TI - Standardized 'no-touch' donor tissue preparation for DALK and DMEK: harvesting undamaged anterior and posterior transplants from the same donor cornea. AB - PURPOSE: To describe a standardized 'no-touch' harvesting technique of anterior and Descemet membrane (DM) grafts for use in deep anterior lamellar keratoplasty (DALK) and Descemet membrane endothelial keratoplasty (DMEK), which provides undamaged anterior and posterior corneal grafts. METHODS: A retrospective evaluation was performed of our standard method for harvesting DM grafts and DALK grafts (Technique I; n = 31) versus a newly designed 'no-touch' technique (Technique II; n = 31), in which a peripheral ring of trabecular meshwork tissue is left in-situ, and the DM graft is trephined on an underlying soft contact lens. Endothelial cell density (ECD) before and immediately after DM stripping was used as the main outcome parameter. RESULTS: Endothelial cell density did not differ within Techniques I and II (before versus after DM stripping) (p = 0.75 and p = 0.54, respectively) or among Techniques I and II (p = 0.61). With the latter technique, anterior corneal grafts and posterior DM grafts could be harvested with negligible damage to the endothelial cell layer or the posterior stromal bed. All 93 grafts (62 DM grafts) were eligible for transplantation, and six months post-operatively all transplants used were functional. CONCLUSION: The new technique offers the following advantages: (i) production of 'undamaged' grafts for DALK and DMEK, (ii) better controlled tissue handling of the thin DM graft during DM stripping and (iii) an increase in availability of corneal grafts obtained from the same donor tissue pool. PMID- 22672203 TI - A systematic review of the impact of weight loss on cancer incidence and mortality. AB - Obesity is well recognized as a significant risk factor for certain cancers; however, a corresponding risk reduction with weight loss is not yet clearly defined. This review aims to examine the literature investigating the effect of all types of weight loss on cancer incidence and mortality, and to more clearly describe the relationship between these two factors. A literature search identified 34 publications reporting weight loss data in relation to cancer incidence or mortality. All except one were observational studies and the majority used self-reported weights and did not define intentionality of weight loss. 16/34 studies found a significant inverse association between weight loss and cancer incidence or mortality. The remainder returned null findings. The observed association was more consistently seen in studies that investigated the effect of intentional weight loss (5/6 studies) and the risk reduction was greatest for obesity-related cancers and in women. In conclusion, intentional weight loss does result in a decreased incidence of cancer, particularly female obesity-related cancers. However, there is a need for further evaluation of sustained intentional weight loss in the obese with less reliance on self reported weight data and more focus on male populations. PMID- 22672204 TI - Main occluding area in partially edentulous patients: changes before and after implant treatment. AB - The 'main occluding area', the location where food crushing occurs during the first stroke of mastication, is reported to be an important concept; however, it is currently limited to findings in individuals with normal dentition. The purpose of this study was to assess the changes in the location, area and bite force of the main occluding area before and after implant treatments. We enrolled 50 partially edentulous and 22 normally dentate subjects. To identify the location of the main occluding area, each subject was instructed to freely bite once on a dental stopping using the partially edentulous side or the normally dentate area. The location, occluding contact area and bite force of the main occluding area before and after the implant treatments were analysed. The main occluding area was located at a reproducible location in the partially edentulous and normally dentate subjects. This location was principally the first molar region, and for the partially edentulous patients with missing teeth in the molar regions, it moved from the premolar region to the first molar region after treatment. The occluding contact area and bite force for the main occluding area increased (P < 0.05) after the implant treatment in the partially edentulous patients with missing teeth in the molar regions. These results suggest that the main occluding area can be restored to the first molar region after implant treatment and may be an important factor in the assessment of prosthodontic treatment. PMID- 22672205 TI - Mycoplasma pneumoniae and mucositis--part of the Stevens-Johnson syndrome spectrum. AB - BACKGROUND: Mycoplasma pneumoniae may induce mucosal inflammation, referred to as M. pneumoniae-associated mucositis (MPAM). There is no generally accepted definition of MPAM, since there may be mucosal lesions only, or mucosal and minimal skin lesions. PATIENTS AND METHODS: We conducted a literature review of MPAM, paying particular attention to pathogenesis, clinical manifestations, treatment decisions, and prognosis. RESULTS: We identified 32 cases of MPAM (median age 13.5 years), whereof 23 patients were otherwise healthy children and young adolescents (72%). M. pneumoniae infection was associated with fever and respiratory symptoms in all calls; it was confirmed by serology (n = 30) and/or PCR (n = 9). Oral lesions were present in all cases, followed by ocular (97%) and uro-genital lesions (78%). Despite the syndrome's name postulating the absence of cutaneous involvement, minimal skin lesions occurred in 31%. Treatment regimens included systemic antibiotics (100%) and systemic anti-inflammatory treatment with corticosteroids (31%) or immunoglobulins (9%). Macrolides were given in 81%, with failure, relapse, and/or worsening in one-third of patients. No patient suffered long-term sequelae. CONCLUSION: MPAM is a distinct extra-pulmonary manifestation falling into the continuum of Stevens-Johnson syndrome. This entity may be due to inflammatory mechanisms suggesting that systemic anti-inflammatory treatment is even more important than antimicrobials. PMID- 22672206 TI - Myogenic regional responsiveness to cholinergic and vipergic stimulation in human colon. AB - BACKGROUND: Differences in the actions of enteric neurotransmitters on colonic circular and longitudinal muscle layers have not been clearly determined, nor the possible existence of intrinsic myogenic phenotypes that might contribute to regional differences in human colon motor activity. The aim of this study was to analyze the direct pharmaco-mechanical coupling of carbachol (CCh) and vasoactive intestinal polypeptide (VIP) on human colonic smooth muscle strips and cells. METHODS: Circular and longitudinal muscle strips and cells were obtained from 15 human specimens of ascending and sigmoid colon. Both isometric tension on muscle strips and contraction and relaxation on cells were measured in response to increasing CCh and VIP concentrations. KEY RESULTS: Circular muscle strips of ascending colon were more sensitive to the effect of CCh than that of sigmoid colon, EC(50) values being, respectively, 4.15MUmolL(-1) and 8.47MUmolL(-1) (P<0.05), although there were no differences in maximal responses. No regional differences were observed in longitudinal muscle strips or in smooth muscle cells. Maximal responses to CCh were higher on circular than longitudinal muscle strips and cells throughout the colon. A greater sensitivity to VIP was observed in ascending colon compared with sigmoid colon, both in circular (EC(50:) 0.041 and 0.15MUmolL(-1) , respectively, P<0.01) and longitudinal (EC(50:) 0.043 and 0.09MUmolL(-1) , respectively, P<0.05) strips, and similar differences were observed in longitudinal smooth muscle cells (EC(50:) 44.85 and 75.24nmolL(-1) , respectively, P<0.05). CONCLUSIONS & INFERENCES: Regional myogenic differences in pharmaco-mechanical coupling between the enteric neurotransmitters and smooth muscle contribute to the complex regional motor patterns of human colon. PMID- 22672207 TI - Lesions of the orbital prefrontal cortex impair the formation of attentional set in rats. AB - In rats, reversal learning impairments are commonly reported after lesions of the orbital prefrontal cortex (OFC), in contrast to the effect of lesions of the medial prefrontal cortex, which impair attentional set-shifting. Comparable dissociations have also been reported in humans, monkeys and mice. However, these two manifestations of behavioural flexibility may share common cognitive processes. The present study tested the hypothesis that lesions of the OFC (an area that integrates expected and actual outcomes to signal which cues in the environment predict reward) would impair the formation of attentional set as well as impairing reversal learning. We compared the performance of lesioned and control rats on two set-shifting tasks. The first task we used, 'the 4ID task', had no reversal stages, but multiple intradimensional acquisitions before the extradimensional shift stage, to assess set-formation as well as set-shifting. The second task was the standard intradimensional/extradimensional '7-stage task', which includes reversal learning stages after each compound acquisition. Compared with controls, lesioned rats were slower to form attentional set on the 4ID task. When they did form a set, they required more trials to complete the extradimensional shift stage. On the 7-stage task, we replicated our previous finding of impaired reversal learning and reduced shift-costs. We interpret these findings as reflecting a single deficit in identifying relevant cues after unexpected outcomes, which supports recent models of OFC function. Our findings challenge the assumption that the contribution of the OFC to behavioural flexibility is limited to reversal learning. PMID- 22672208 TI - Mexican American female adolescents' perceptions of relationships and dating violence. AB - PURPOSE: This study fills a gap regarding the perspectives of Mexican American female adolescents on dating relationships and dating violence (DV). METHODS: This was a qualitative descriptive study. Focus groups included 20 Mexican American young women, primarily first and second generation, mean age 14.5 years (SD= 2.5). Data were analyzed with categorical analysis. FINDINGS: Participants described key components of DV and identified cultural aspects that may serve to promote healthy dating relationships. CONCLUSIONS: Family-based interventions to promote exploration of gender roles and parent-child communication may foster biculturalism as well as promote healthy dating relationships and prevent violence within this cultural group. CLINICAL RELEVANCE: In the United States, 10% to 40% of teens experience DV. Hispanic females experience more physical DV than their White peers. PMID- 22672209 TI - Copy number variations in normal karyotype acute myeloid leukaemia and their association with treatment response. AB - Copy number variation (CNV) has been reported to be associated with chemotherapy response, which affects disease prognosis. Here, we determined the frequency of genome-wide cytogenetic CNV aberrations in Korean patients with normal karyotype (NK) acute myeloid leukaemia (AML) and tested whether these genomic variations contribute to differences in Ara-C and anthracycline-based chemotherapy responses. Bone marrow aspirates and blood from 30 previously untreated de novo NK-AML patients were provided at the time of diagnosis for copy number analysis. Possible associations between cytogenetic aberrations and clinical parameters were analysed. CNVs were identified in 23 (76.7%) of the 30 cases tested. Multivariate analyses controlled for other clinical co-variates showed that patients having copy number loss had a decreased probability of complete remission (OR, 0.015 [95% CI, 0-0.737], p = 0.035). Patients who had a copy number gain of more than four regions tended to have shorter event-free survival (EFS) (p = 0.083) with multivariate analysis showing that CNV increase is an independent predictive factor for shorter EFS (HR, 22.104 [95% CI, 1.644 297.157], p = 0.020). In addition, we identified candidate genes that may be involved in Ara-C and anthracycline drug response in Korean patients with NK-AML. These results suggest that CNVs may affect the success of Ara-C and anthracycline based chemotherapy in Korean patients with NK-AML. PMID- 22672210 TI - Are adults with intellectual disabilities socially excluded? An exploratory study in Taiwan. AB - BACKGROUND: The aim of this exploratory study is to examine to what extent adults with intellectual disabilities (ID) in Taiwan are socially excluded and to identify the factors that are potentially associated with such social exclusion. METHODS: The research method of this study is secondary data analysis, using descriptive and chi2 statistical analysis. Two data sets, from the 2003 and 2006 surveys entitled 'Survey of Living Situation for People with Disabilities in Taiwan', were used (n = 572; n = 618). In addition, 'independent living/living within the community' (as opposed to residing in an institution), 'employment' and 'household economic situation/residing in a low-income household' were social exclusion indicators in this study. RESULTS: The results revealed that in the 2003 (2006) survey, 81.9% (79.6%) of the subjects fell into at least one category of social exclusion, 11.3% (12.3%) fell into two or more categories and 0.2% (1.1%) fell into all three categories. Moreover, older women with ID, with no spouse or partner, lower educational levels and greater severity of the disability had a significantly greater likelihood of being subjected to more categories of social exclusion. CONCLUSIONS: The finding that the proportion of adults with ID and no social exclusion has risen from 18.1% in 2003 to 20.4% in 2006 represents an encouraging trend. However, there has been a marked increase in the proportion of the subjects with more categories of social exclusion, particularly with regard to those who have to endure all three categories, from 0.2% in 2003, to 1.1% in 2006. This implies that, at the time of the last survey, there was still considerable room for improvement in the social inclusion of adults with ID in Taiwan. PMID- 22672211 TI - Combined spinal cord and peripheral nerve field stimulation for persistent post herniorrhaphy pain. AB - OBJECTIVES: Chronic post-hernia pain is a common complication after inguinal herniorrhaphies. Peripheral nerve field stimulation (PNFS) and spinal cord stimulation (SCS) are two new promising treatment modalities. Four patients with persistent neuropathic post-hernia pain were recruited for this prospective study. MATERIALS AND METHODS: Electrodes were inserted into the epidural space of the spinal canal and into the subcutaneous tissue in the inguinal region during a single surgical procedure. During a 14-day trial, double-blind stimulation was performed via an external stimulator: three days using the spinal electrode (SCS), three days using the inguinal electrode (PNFS), three days using both (SCS + PNFS), and five days off, with an alternating order from patient to patient. During the trial, pain intensity was assessed thrice daily by the visual analog scale. Additionally, pain intensity and quality of life (QOL) were assessed before and after surgical intervention by the Brief Pain Inventory, SF36 scale, and Pain Disability Index. RESULTS: All patients had a marked pain reduction during the trial phase, and this reduction was more prominent when both electrodes were activated simultaneously (p < 0.001). At the late follow-up, a significant pain reduction and improvement of QOL was observed in three patients. CONCLUSIONS: Both SCS and PNFS are effective in treating post-hernia pain, but the magnitude of pain reduction was more prominent with concomitant stimulation. Combined PNFS and SCS should be considered for patients with a less than optimal response to either SCS or PNFS. More studies are necessary to address the cost effect issues of this new approach to treatment. PMID- 22672213 TI - Nanosilver as a novel agent in keloid therapy. PMID- 22672212 TI - Salivary gland hypofunction induced by activation of innate immunity is dependent on type I interferon signaling. AB - BACKGROUND: Activation of innate immunity through polyinosinic:polycytidylic acid [poly(I:C)] causes acute salivary gland hypofunction. As a major consequence of poly(I:C) treatment is type I interferon (IFN) production, this study was undertaken to investigate their role in salivary gland dysfunction. METHODS: Different strains of mice deficient in either interferon alpha receptor (IFNAR1( /-)) or IL-6(-/-), or IL-10(-/-), or EBI3(-/-) were treated with poly(I:C). Salivary gland function was determined by measuring pilocarpine-induced saliva volume. Gene expression levels were measured by real-time PCR. Ca(2+) mobilization studies were performed using ex-vivo acinar cells. RESULTS: A single injection of poly(I:C) rapidly induced salivary gland hypofunction in wild-type B6 mice (41% drop in saliva volumes compared to PBS-treated mice). In contrast, the loss of function in poly(I:C)-treated IFNAR(-/-) mice was only 9.6%. Gene expression analysis showed reduced levels of Il-6, Il-10, and Il-27 in submandibular glands of poly(I:C)-treated IFNAR(-/-) mice. While salivary gland dysfunction in poly(I:C)-treated IL-10(-/-) and EBI3(-/-) mice was comparable to wild-type mice, the IL-6(-/-) mice were more resistant, with only a 21% drop in function. Pilocarpine-induced Ca(2+) flux was significantly suppressed in acinar cells obtained from poly(I:C)-treated wild-type mice. CONCLUSIONS: Our data demonstrate that a combined action of type I IFNs and IL-6 contributes toward salivary gland hypofunction. This happens through interference with Ca(2+) mobilization within acinar cells. Thus, in acute viral infections and diseases like Sjogren's syndrome, elevated levels of type I IFNs and IL-6 can directly affect glandular function. PMID- 22672214 TI - A prospective randomised controlled trial of Nd:YAG laser photocoagulation versus liquid paraffin plus antiseptic cream in the treatment of recurrent epistaxis. AB - OBJECTIVES: To evaluate the efficacy of Nd:YAG laser photocoagulation with that of liquid paraffin plus antiseptic cream in the management of recurrent epistaxis. DESIGN: Prospective clinical study. Eighty consecutive patients with histories of recurrent epistaxis were randomly assigned to receive treatment in an outpatient setting consisting of either a combination of liquid paraffin plus antiseptic cream (group 1) or Nd:YAG laser photocoagulation (group 2). SETTING: University-affiliated teaching hospital. PARTICIPANTS: Eighty consecutive patients who suffered from recurrent anterior epistaxis presented to the Otolaryngology Department at the Eye and ENT Hospital, Fudan University between February 2011 and June 2011. MAIN OUTCOME MEASURES: The following outcome measures were assessed: bleeding intensity, bleeding frequency 4 and 12 weeks after treatment (0 = no bleeding, 1 = reduced bleeding, 2 = the same, 3 = worse), participant's perception of discomfort during the management (grade 0-10, where 10 is the worst pain) and complications. RESULTS: At 12 weeks, 85% of laser patients versus 40% of control patients had no reported bleeding. The outcome score at 4 weeks after treatment showed no significant difference between the two groups (P = 0.130, P > 0.05); however, the outcome score at 12 weeks after treatment showed a significant difference between the two groups (P = 0.000, P < 0.01). The median and mean +/- sd pain levels experienced were 5.0 and 5.2 +/- 2.2. Both groups had no complications. CONCLUSIONS: It can be concluded that Nd:YAG laser photocoagulation is a preferable therapy in the treatment of recurrent epistaxis, especially in terms of long-lasting efficacy. The level of pain associated with the procedure was tolerated. It is a simple, easy, safe and rapid therapy, which can be performed in an office setting. PMID- 22672215 TI - Incidence of post-stroke delirium and 1-year outcome. AB - INTRODUCTION: Post-stroke delirium is not uncommon, and is associated with poorer outcome, higher mortality, longer hospital stay and greater risk of post-stroke dementia. We aim to identify the incidence of post-stroke delirium, risk factors for its development and 1-year outcome. METHOD: Consecutive patients aged >50 years admitted to the acute stroke unit were recruited. Baseline demographic data, types of stroke, location of infarct, etiology of stroke, premorbid cognitive impairment, living arrangement, comorbidity, drug history and biochemical parameters were collected. Delirium was screened by the Confusion Assessment Method. Outcome data included length of stay, mortality, functional mobility, and placement on discharge 6 months and 12 months post-stroke. RESULTS: A total of 314 patients with a mean age of 72.9 years were recruited. Of those patients, 86 (27.4%) had delirium. Age (OR 1.05), presence of acute urinary retention (OR 7.67), chest infection (OR 22), National Institutes of Health Stroke Scale (OR 1.13), total anterior circulation infarct (OR 18.8), posterior circulation infarct (OR 3.52) and pre-existing cognitive impairment (OR 2.51) were independent predictors of post-stroke delirium. Patients with delirium had more functional disability, a higher proportion went to a nursing home on discharge (62% vs 11.2%), at 6 months (60% vs 12.5%) and at 12 months (65% vs 13%), and there was higher inpatient mortality (18% vs 2.2%) and 1-year mortality (30% vs 7.4%). Hospital stay was also longer (45 vs 22 days). CONCLUSION: Delirium is a common complication post-stroke, with treatable risk factors. It results in higher functional impairment, nursing home placement and mortality. Comprehensive geriatric assessment of older stroke patients might help to reduce the occurrence of delirium. PMID- 22672216 TI - The WISTAH hand study: a prospective cohort study of distal upper extremity musculoskeletal disorders. AB - BACKGROUND: Few prospective cohort studies of distal upper extremity musculoskeletal disorders have been performed. Past studies have provided somewhat conflicting evidence for occupational risk factors and have largely reported data without adjustments for many personal and psychosocial factors. METHODS/DESIGN: A multi-center prospective cohort study was incepted to quantify risk factors for distal upper extremity musculoskeletal disorders and potentially develop improved methods for analyzing jobs. Disorders to analyze included carpal tunnel syndrome, lateral epicondylalgia, medial epicondylalgia, trigger digit, deQuervain's stenosing tenosynovitis and other tendinoses. Workers have thus far been enrolled from 17 different employment settings in 3 diverse US states and performed widely varying work. At baseline, workers undergo laptop administered questionnaires, structured interviews, two standardized physical examinations and nerve conduction studies to ascertain demographic, medical history, psychosocial factors and current musculoskeletal disorders. All workers' jobs are individually measured for physical factors and are videotaped. Workers are followed monthly for the development of musculoskeletal disorders. Repeat nerve conduction studies are performed for those with symptoms of tingling and numbness in the prior six months. Changes in jobs necessitate re-measure and re-videotaping of job physical factors. Case definitions have been established. Point prevalence of carpal tunnel syndrome is a combination of paraesthesias in at least two median nerve served digits plus an abnormal nerve conduction study at baseline. The lifetime cumulative incidence of carpal tunnel syndrome will also include those with a past history of carpal tunnel syndrome. Incident cases will exclude those with either a past history or prevalent cases at baseline. Statistical methods planned include survival analyses and logistic regression. DISCUSSION: A prospective cohort study of distal upper extremity musculoskeletal disorders is underway and has successfully enrolled over 1,000 workers to date. PMID- 22672217 TI - How common is the ability of extrafloral nectaries to produce nectar droplets, to secrete nectar during the night and to store starch? AB - Evidence in favour of the ability of extrafloral nectaries (EFNs) to form nectar drop(let)s, secrete extrafloral nectar (EFNec) also during the night and store starch was compiled in order to refute controversial assertions. Not only were more than 150 reports of direct observations of EFNec drop(let)s found, but also 90 studies which suggest that EFNec secretion is copious enough to form drop(let)s automatically by forces of physics (surface tension strength), provided nectar accumulation is not interrupted by predatory animals. Twenty direct observations of nocturnal production of EFNec sufficiently proved that it is not always produced during the day. Additionally, numerous observations of the nocturnal activities of nectar consumers on EFNs indirectly indicated very common nocturnal secretion of EFNec. Although there is an early report of a starch containing EFN from 1881 (Trelease), few similar observations in other EFNs followed. Nevertheless, four studies have described the disappearance of stored starch during secretion and senescence of the EFNs. Referring back to an apparent relationship between the degradation of starch stored in a floral nectary and programmed cell death, at least in EFNs with transient storage of starch, a similar relationship cannot be excluded. PMID- 22672218 TI - Pharmacologic preconditioning therapy prior to atrial septal defect closure in patients at high risk for acute pulmonary edema. AB - OBJECTIVES: The aim of this study was to assess whether transient atrial septal defect (ASD) occlusion and, if required, vasodilator therapy would improve the safety of percutaneous ASD closure in high-risk subsets. BACKGROUND: While percutaneous ASD closure is generally considered a low risk intervention, hypertensive and elderly patients may develop pulmonary edema following the procedure because of underlying left ventricular (LV) diastolic dysfunction. METHODS: Fifty-two consecutive patients who underwent successful percutaneous ASD closures were enrolled into a single-center prospective registry. Patients with arterial hypertension and/or >60 years of age (n = 15) were considered at risk for periprocedural pulmonary edema. Those patients were tested for an increase of LV filling pressures during transient ASD occlusion and, if this was the case, treated according to a prespecified algorithm. Clinical and echocardiography data were collected in-hospital and at 6 months follow-up. RESULTS: Shunt size was comparable in high and standard-risk patients (Qp:Qs 2.1 +/- 0.8 vs. 2.1 +/- 0.7, P = 0.82). High-risk patients had more often pulmonary hypertension (58% vs. 14%, P < 0.05) and were more frequently symptomatic. Among them, 4/15 (27%) demonstrated a significant rise of left-sided filling pressures during transient ASD balloon occlusion and underwent pharmacologic preconditioning prior to ASD closure. None of them developed periprocedural pulmonary edema. At follow-up, patients were less symptomatic (Pre: NYHA II n = 15, NYHA III n = 9; Post: NYHA II n = 15, NYHA III n = 0; P = 0.02) and right ventricular size decreased from 23 +/- 5 cm(2) to 17 +/- 5 cm(2), P < 0.05. CONCLUSION: Transient ASD occlusion and, if required, pharmacologic preconditioning prior to percutaneous closure may prevent periprocedural pulmonary edema in high-risk patients. PMID- 22672219 TI - Softness sensor system for simultaneously measuring the mechanical properties of superficial skin layer and whole skin. AB - BACKGROUND/AIMS: Few attempts have been made to distinguish the softness of different skin layers, though specific measurement of the superficial layer would be useful for evaluating the emollient effect of cosmetics and for diagnosis of skin diseases. MATERIALS AND METHODS: We developed a sensor probe consisting of a piezoelectric tactile sensor and a load cell. To evaluate it, we firstly measured silicone rubber samples with different softness. Then, it was applied to human forearm skin before and after tape-stripping. A VapoMeter and skin-surface hygrometer were used to confirm removal of the stratum corneum. A Cutometer was used to obtain conventional softness data for comparison. RESULTS AND CONCLUSIONS: Both the piezoelectric tactile sensor and the load cell could measure the softness of silicone rubber samples, but the piezoelectric tactile sensor was more sensitive than the load cell when the reaction force of the measured sample was under 100 mN in response to a 2-mm indentation. For human skin in vivo, transepidermal water loss and skin conductance were significantly changed after tape-stripping, confirming removal of the stratum corneum. The piezoelectric tactile sensor detected a significant change after tape-stripping, whereas the load cell did not. Thus, the piezoelectric tactile sensor can detect changes of mechanical properties at the skin surface. The load cell data were in agreement with Cutometer measurements, which showed no change in representative skin elasticity parameters after tape-stripping. These results indicate that our sensor can simultaneously measure the mechanical properties of the superficial skin layer and whole skin. PMID- 22672220 TI - Conventional and modified veneered zirconia vs. metalloceramic: fatigue and finite element analysis. AB - PURPOSE: The purpose of this study was to test the hypothesis that all-ceramic crown core-veneer system reliability is improved by modifying the core design and as a result is comparable in reliability to metal-ceramic retainers (MCR). Finite element analysis (FEA) was performed to verify maximum principal stress distribution in the systems. MATERIALS AND METHODS: A first lower molar full crown preparation was modeled by reducing the height of proximal walls by 1.5 mm and occlusal surface by 2.0 mm. The CAD-based preparation was replicated and positioned in a dental articulator for specimen fabrication. Conventional (0.5 mm uniform thickness) and modified (2.5 mm height, 1 mm thickness at the lingual extending to proximals) zirconia (Y-TZP) core designs were produced with 1.5 mm veneer porcelain. MCR controls were fabricated following conventional design. All crowns were resin cemented to 30-day aged composite dies, aged 14 days in water and either single-loaded to failure or step-stress fatigue tested. The loads were positioned either on the mesiobuccal or mesiolingual cusp (n = 21 for each ceramic system and cusp). Probability Weibull and use level probability curves were calculated. Crack evolution was followed, and postmortem specimens were analyzed and compared to clinical failures. RESULTS: Compared to conventional and MCRs, increased levels of stress were observed in the core region for the modified Y-TZP core design. The reliability was higher in the Y-TZP-lingual modified group at 100,000 cycles and 200 N, but not significantly different from the MCR-mesiolingual group. The MCR-distobuccal group showed the highest reliability. Fracture modes for Y-TZP groups were veneer chipping not exposing the core for the conventional design groups, and exposing the veneer-core interface for the modified group. MCR fractures were mostly chipping combined with metal coping exposure. CONCLUSIONS: FEA showed higher levels of stress for both Y-TZP core designs and veneer layers compared to MCR. Core design modification resulted in fatigue reliability response of Y-TZP comparable to MCR at 100,000 cycles and 200 N. Fracture modes observed matched with clinical scenarios. PMID- 22672221 TI - Progression of subclinical myocardial dysfunction in type 2 diabetes after 5 years despite improved glycemic control. AB - BACKGROUND: Patients with uncomplicated diabetes have reduced left ventricular long-axis function, related to poor glycemic control and increased conduit arterial stiffness, with increased radial function. It is unknown if improved control of risk factors can reverse these subclinical changes. PATIENTS AND METHODS: We studied 27 patients with type 2 diabetes (18 men) 57 +/- 1 months (mean +/- SD) after an initial visit when they were compared with healthy age- and sex-matched controls. On both visits patients had detailed echocardiographic studies including tissue Doppler, noninvasive tests of conduit arterial function, and metabolic and lipid profiling. RESULTS: Mean age at this second review was 63.4 +/- 8.1 years; 48% of patients received insulin. Mean HbA1c had decreased by 13% to 8 +/- 1.6% and cholesterol by 17% to 4.3 +/- 1.3 mmol/L (both, P < 0.01), but long-axis systolic and early diastolic myocardial velocities had also declined, by 13% and 20%, respectively (both, P < 0.001). Body mass index had increased by 4%, arterial pulse pressure by 17% (both P < 0.01), and carotid arterial stiffness by 49% (P < 0.01). Fractional shortening (by 21%, P < 0.001), radial systolic velocity (by 13%, P < 0.05), and ejection fraction (by 9% to 68 +/- 7%, P < 0.01) had all declined. Reductions in longitudinal function were best predicted by its baseline measurements, duration of diabetes, fasting triglycerides, and arterial stiffness (epsilon index). CONCLUSIONS: Despite improved diabetic control, subclinical left ventricular dysfunction progressed over 5 years. Radial compensation was reversed. Prevention of subclinical myocardial dysfunction in diabetes might require more intensive control of net cardiovascular risk. PMID- 22672222 TI - Deciphering the genomic structure, function and evolution of carotenogenesis related phytoene synthases in grasses. AB - BACKGROUND: Carotenoids are isoprenoid pigments, essential for photosynthesis and photoprotection in plants. The enzyme phytoene synthase (PSY) plays an essential role in mediating condensation of two geranylgeranyl diphosphate molecules, the first committed step in carotenogenesis. PSY are nuclear enzymes encoded by a small gene family consisting of three paralogous genes (PSY1-3) that have been widely characterized in rice, maize and sorghum. RESULTS: In wheat, for which yellow pigment content is extremely important for flour colour, only PSY1 has been extensively studied because of its association with QTLs reported for yellow pigment whereas PSY2 has been partially characterized. Here, we report the isolation of bread wheat PSY3 genes from a Renan BAC library using Brachypodium as a model genome for the Triticeae to develop Conserved Orthologous Set markers prior to gene cloning and sequencing. Wheat PSY3 homoeologous genes were sequenced and annotated, unravelling their novel structure associated with intron loss events and consequent exonic fusions. A wheat PSY3 promoter region was also investigated for the presence of cis-acting elements involved in the response to abscisic acid (ABA), since carotenoids also play an important role as precursors of signalling molecules devoted to plant development and biotic/abiotic stress responses. Expression of wheat PSYs in leaves and roots was investigated during ABA treatment to confirm the up-regulation of PSY3 during abiotic stress. CONCLUSIONS: We investigated the structural and functional determinisms of PSY genes in wheat. More generally, among eudicots and monocots, the PSY gene family was found to be associated with differences in gene copy numbers, allowing us to propose an evolutionary model for the entire PSY gene family in Grasses. PMID- 22672223 TI - Parental bonding in males with adjustment disorder and hyperventilation syndrome. AB - BACKGROUND: The purpose of the study was to identify the style of parental bonding and the personality characteristics that might increase the risk of hyperventilation and adjustment disorder. METHODS: A total of 917 males were recruited, 156 with adjustment disorder and hyperventilation syndrome (AD + HY), 273 with adjustment disorder without hyperventilation syndrome (AD-HY), and 488 healthy controls. All participants completed the Parental Bonding Instrument, Eysenck Personality Questionnaire, and Chinese Health Questionnaire. RESULTS: Analysis using structural equation models identified a pathway relationship in which parental bonding affected personality characteristics, personality characteristics affected mental health condition, and mental health condition affected the development of hyperventilation or adjustment disorder. Males with AD-HY perceived less paternal care, and those with AD + HY perceived more maternal protection than those with adjustment disorder and those in the control group. Participants with AD-HY were more neurotic and less extroverted than those with AD + HY. Both groups showed poorer mental health than the controls. CONCLUSIONS: Although some patients with hyperventilation syndrome demonstrated symptoms of adjustment disorder, there were different predisposing factors between the two groups in terms of parental bonding and personality characteristics. This finding is important for the early intervention and prevention of hyperventilation and adjustment disorder. PMID- 22672224 TI - Spontaneous resolution of severe, symptomatic mesocolic panniculitis: a case report. AB - BACKGROUND: Mesenteric panniculitis is a rare chronic fibrosing inflammatory disease that typically affects the adipose tissue and mesentery of the small intestine but may also affect the mesosigmoid and the mesocolon. The pathology of this disease remains unclear despite association with some malignancies or inflammatory disorders. We report a case of mesocolic panniculitis and a literature review of its clinical presentation, imaging findings, associated conditions and treatment options. CASE PRESENTATION: A 64 year-old Caucasian man was admitted to the gastroenterology department for severe weakness, left lower quadrant abdominal pain, weight loss and diarrhoea. Physical examination revealed a palpable firm mass occupying the entire left part of the abdomen. Abdominal CT scan showed fatty infiltration of the mesosigmoid and left mesocolic fat which was strongly suggestive of panniculitis. Laparoscopic surgery revealed an inflamed and edematous mesocolon and mesosigmoid; the sigmoid mucosa appeared petechial which was suggestive of venous ischemia. Histological examination of surgical biopsies revealed mesocolic panniculitis. Despite exhaustive investigation, no associated conditions were found and the cause was classified as idiopathic. Surprisingly, the patient clinically improved without therapeutic intervention other than supportive care. CONCLUSION: Although mesenteric panniculitis is most often a radiographic diagnosis without clinical symptomatology, it can also present with significant general status alteration. We report a case of mesocolic panniculitis complicated by development of an inflammatory mass associated with ischemic colitis. Mesenteric panniculitis is a difficult diagnosis to make which typically requires histologic confirmation. The overall prognosis is good with supportive treatment. PMID- 22672226 TI - Surgical treatment of a complete symptomatic ossification of quadratus femoris muscle in a young haemophilic patient. PMID- 22672225 TI - Dealing with heterogeneous populations in randomized wound trials: challenges and potential solutions. AB - Chronic wounds have a great variety of etiologies and manifestations that influence wound healing. Such heterogeneity potentially threatens the validity and clinical usefulness of trials if not considered appropriately. In 82 randomized wound trials retrieved from 10 Cochrane reviews, we assessed if and how authors considered wound and other prognostically important characteristics in the conduct and analysis of wound trials. We assessed whether these characteristics were discussed, reflected in the eligibility criteria, used for prestratification or for adjustments to ensure comparability of treatment groups, and whether subgroup analyses were conducted to identify heterogeneity of treatment effects. Nine percent of all trials explicitly discussed characteristics that influence wound healing in the introduction and 43% in the Discussion section. Ninety percent of trials had at least one prognostically important characteristic as eligibility criterion. Only 11% of trials used prestratification, and 6% adjusted the results for imbalances between treatment groups. Twenty-seven percent performed subgroup analyses with prognostically important characteristics defining subgroups. Chronic wound trials use simple randomization, but rarely adapt the study design and analysis to take the heterogeneity of patients into consideration. Collaborative multicenter trials would overcome many of the limitations and provide statistical power to detect important treatment effects both overall and in subgroups. PMID- 22672227 TI - Femoral-gluteal adiposity is not associated with insulin sensitivity in type 1 diabetes. AB - AIMS: To quantify and compare associations between femoral-gluteal adiposity and insulin sensitivity in adults with Type 1 diabetes mellitus with adults with normal glucose tolerance. METHODS: Individuals with Type 1 diabetes (n = 28) were recruited from the Pittsburgh Epidemiology of Diabetes Complication study, a 24 year prospective study of childhood-onset diabetes, and compared cross sectionally with individuals with normal glucose tolerance (n = 56) of similar age, sex and BMI. Insulin sensitivity was defined as whole-body glucose disposal measured by hyperinsulinaemic-euglycaemic clamps. Adiposity was quantified by dual energy X-ray absorptiometry. RESULTS: Individuals with Type 1 diabetes exhibited lower insulin sensitivity (5.8 vs. 8.2 mg min(-1) kg fat-free mass(-1), P < 0.01), lower total fat mass (20.1 vs. 29.0 kg, P < 0.001) and lower proportional leg fat mass (36.0 vs.37.7%, P = 0.03), but similar proportional trunk fat (% trunk fat mass) compared with individuals with normal glucose tolerance. Overall, results from linear regression demonstrated that higher % leg fat mass (P < 0.01) and lower % trunk fat mass (P < 0.01) were independently associated with lower insulin sensitivity after adjustments for age, sex, height, total fat mass (kg) and diabetes status. Higher % leg fat mass was independently associated with higher insulin sensitivity in individuals with normal glucose tolerance (P < 0.01) after similar adjustment; significant associations were not observed in Type 1 diabetes. CONCLUSIONS: Reduced insulin sensitivity is a prominent feature of Type 1 diabetes and is associated with total and abdominal adiposity. Compared with adults with normal glucose tolerance, leg fat mass does not show any positive association with insulin sensitivity in Type 1 diabetes. PMID- 22672229 TI - Effects of bipolar and monopolar transurethral resection of the prostate on urinary and erectile function: a prospective randomized comparative study. AB - OBJECTIVE: To evaluate the outcomes of bipolar vs conventional monopolar transurethral resection of the prostate (TURP) on urinary and erectile function. MATERIAL AND METHODS: A total of 286 patients with benign prostatic hyperplasia (BPH) were randomized to bipolar or monopolar conventional TURP treatment groups. Operative and early postoperative variables and complications were recorded and all patients were re-evaluated at 1, 3, 6 and 12 months after surgery using the International Prostate Symptom Score (IPSS), uroflowmetry, post-void residual urine volume (PVR) and the erectile function domain of the International Index of Erectile Function (IIEF-ED). A comparative evaluation of erectile function was performed on 188 preoperatively non-catheterized patients with regular sexual partners. RESULTS: The operating time was shorter in the bipolar TURP group. Postoperative bleeding and blood transfusion requirements did not significantly differ between the two groups. Sodium levels were significantly lower in the monopolar group than in the bipolar group. Transuretheral resection syndrome developed in two (1.4%) patients in the monopolar group. Both groups had similar and significantly improved IPSS values, maximum urinary flow rate values and PVR measurement. ED worsened in 32 (17.0%) patients, improved in 53 (28.2%) patients, and was unchanged in 103 (54.8%) patients. Changes in the IIEF scores during the follow-up period were similar between the bipolar and monopolar groups. CONCLUSION: Bipolar TURP is a safe and effective procedure that is associated with a significantly shorter operating time, a smaller reduction in serum sodium levels and a similar efficacy compared with conventional monopolar TURP. PMID- 22672228 TI - Identifying self-perceived HIV-related stigma in a population accessing antiretroviral therapy. AB - This study identifies factors associated with self-perceived HIV-related stigma (stigma) among a cohort of individuals accessing antiretroviral therapy in British Columbia, Canada. Data were drawn from the Longitudinal Investigations into Supportive and Ancillary Health Services study, which collects social, clinical, and quality of life (QoL) information through an interviewer administered survey. Clinical variables (i.e., CD4 count) were obtained through linkages with the British Columbia HIV/AIDS Drug Treatment Program. Multivariable linear regression was performed to determine the independent predictors of stigma. Our results indicate that among participants with high school education or greater the outcome stigma was associated with a 3.05 stigma unit decrease (95% CI: -5.16, -0.93). Having higher relative standard of living and perceiving greater neighborhood cohesion were also associated with a decrease in stigma ( 5.30 95% CI: -8.16, -2.44; -0.80 95% CI: -1.39, -0.21, respectively). Lower levels of stigma were found to be associated with better QoL measures, including perceiving better overall function (-0.90 95% CI: -1.47, -0.34), having fewer health worries (-2.11 95% CI: -2.65, -1.57), having fewer financial worries ( 0.67 95% CI: -1.12, -0.23), and having less HIV disclosure concerns (-4.12 95% CI: -4.63, -3.62). The results of this study show that participants with higher education level, better QoL measures, and higher self-reported standards of living are less likely to perceive HIV-related stigma. PMID- 22672231 TI - Ocular motor score a novel clinical approach to evaluating ocular motor function in children. AB - PURPOSE: Ocular motility disturbances are common in a number of neuropaediatric and neurometabolic disorders. Assessment of ocular motor function can be a source of information for diagnosis and follow-up of these patients. AIM: To evaluate a new clinical ocular motor function test: ocular motor score (OMS) and provide reference values in children and young adults without known ocular or neurological disorders. MATERIAL AND METHODS: A total of 233 children and young adults, 103 males and 130 females between the ages of 6 months and 19 years, were assessed according to a specific OMS protocol. They were divided into four different age groups: 0.5-3, 4-6, 7-10 and 11-19 years. The OMS protocol consists of 15 different subtests evaluating ocular motor function, and a total score of minimum 0 up to max 15 can be obtained: the minimum score, 0, is considered normal while 1 represents an abnormal function. RESULTS: The median OMS in the whole reference group was 0.3 (range 0-4.8). The median OMS in the different age groups, starting with the youngest, was: 0.9 (range 0.3-4.8), 0.3 (range 0-3.4), 0.3 (range 0-2.3) and 0 (range 0-3.5), respectively. The youngest subjects, aged 0.5-3, showed a significantly higher total OMS compared with the other age groups (p < 0.001). CONCLUSION: This study provides reference values for the OMS test in a population aged 0.5-19 years. The test may be valuable as a screening tool for identification and follow-up of ocular motor dysfunction in children and young adults. PMID- 22672232 TI - Current concepts in hypophosphatasia: case report and literature review. AB - BACKGROUND. Hypophosphatasia (HP) is characterized by defective mineralization of bone and teeth because of deficient alkaline phosphatase activity. There are generally six recognized clinical forms, of which the most severe is often lethal prenatally or early in life. In milder forms, such as odontohypophosphatasia (OHP), premature exfoliation of primary teeth may be the only clinical manifestation. CASE REPORT. A 20-month-old girl was referred to the Specialist Paediatric Salaried Dental Service within the Harrogate and District NHS Foundation Trust with mobility of tooth numbers 71 and 81. Clinical examination revealed grade III mobile 71 and 81, with minimal gingival inflammation and plaque deposits. There were no other dental findings and no significant medical history. Tooth numbers 71 and 81 exfoliated prematurely with no evidence of root resorption, shortly after presentation. Haematological and urinary investigations showed no abnormalities. Histological examination showed a complete absence of cementum. A diagnosis of OHP was made. After 10 months of dental follow-up, no further teeth have increased mobility. CONCLUSION. Odontohypophosphatasia should be included as a differential diagnosis in children presenting with early loss of primary teeth. The dentist may be the first health care professional to whom the patient presents. PMID- 22672233 TI - NLRP10 enhances Shigella-induced pro-inflammatory responses. AB - Members of the NLR family evolved as intracellular sensors for bacterial and viral infection. However, our knowledge on the implication of most of the human NLR proteins in innate immune responses still remains fragmentary. Here we characterized the role of human NLRP10 in bacterial infection. Our data revealed that NLRP10 is a cytoplasmic localized protein that positively contributes to innate immune responses induced by the invasive bacterial pathogen Shigella flexneri. SiRNA-mediated knock-down studies showed that NLRP10 contributes to pro inflammatory cytokine release triggered by Shigella in epithelial cells and primary dermal fibroblasts, by influencing p38 and NF-kappaB activation. This effect is dependent on the ATPase activity of NLRP10 and its PYD domain. Mechanistically, NLRP10 interacts with NOD1, a NLR that is pivotally involved in sensing of invasive microbes, and both proteins are recruited to the bacterial entry point at the plasma membrane. Moreover, NLRP10 physically interacts with downstream components of the NOD1 signalling pathway, such as RIP2, TAK1 and NEMO. Taken together, our data revealed a novel role of NLRP10 in innate immune responses towards bacterial infection and suggest that NLRP10 functions as a scaffold for the formation of the NOD1-Nodosome. PMID- 22672235 TI - Abstracts of the RCOG (Royal College of Obstetricians and Gynaecologists) 10th International Scientific Congress. June 5-8, 2012. Kuching, Sarawak, Malaysia. PMID- 22672236 TI - Hyperkeratoses as paraneoplastic syndrome. PMID- 22672237 TI - The autonomic response to human esophageal acidification and the development of hyperalgesia. AB - BACKGROUND: Distal esophageal acidification induces variable hyperalgesia in the non-acid exposed proximal esophagus. As the autonomic nervous system (ANS) modulates nociception, the aim was to determine whether autonomic reactivity to acid infusion predicted inter-individual differences in hyperalgesia. METHODS: In 25 healthy volunteers (18 women, age range 22-58, mean 36.5 years), using a double-blind, placebo-controlled crossover design, pain thresholds to electrical stimulation were determined in the proximal esophagus and foot (control) pre and post a 30-min distal esophageal infusion of 0.15 mol L(-1) HCl or saline with autonomic monitoring. Sympathetic Cardiac Sympathetic Index and Skin Conductance Response and parasympathetic Cardiac Vagal Tone and Cardiac Sensitivity to Baroreflex measures were derived. Plasma cortisol was measured pre and post infusion as were anxiety and unpleasantness. KEY RESULTS: Acid infusion reduced group pain threshold in the proximal esophagus (adjusted mean change -5.0 mA vs saline +3.4 mA, P < 0.001), and raised sympathetic measures (Cardiac Sympathetic Index, Skin Conduction Response) and cortisol levels, but reduced parasympathetic measures (cardiac vagal tone and cardiac sensitivity to Baroreflex) (all P < 0.05). Acid infusion also increased anxiety and unpleasantness scores (both P < 0.05). In 16 acid-sensitizers, the degree of hyperalgesia correlated with increasing heart rate (r = -0.66, P = 0.005), and fall in cardiac vagal tone (r = 0.54, P = 0.03) and Cardiac Sensitivity to Baroreflex (r = 0.54, P = 0.03). CONCLUSIONS & INFERENCES: Acid-induced esophageal hyperalgesia correlated with reduced parasympathetic tone, suggesting that the parasympathetic nervous system may have anti hyperalgesic properties. Additional studies on the autonomic modulation of esophageal hyperalgesia are required. PMID- 22672238 TI - Electromyographic power spectrum of jaw muscles during clenching in unilateral temporomandibular joint osteoarthritis patients. AB - The relationship between temporomandibular joints (TMJ) osteoarthritis and masticatory muscle disorders is poorly understood. The data are sparse, the results are conflicting, and electromyographic (EMG) power spectrum analysis has not been used. The aims of this study were to compare the differences in EMG power spectrum during, and pressure pain thresholds (PPTs) before and after, sustained clenching in patients with unilateral TMJ osteoarthritis and healthy control subjects. Nineteen patients with unilateral TMJ osteoarthritis without masticatory muscle pain and 20 control subjects were evaluated. We measured EMG amplitudes at maximum voluntary contraction, median frequency from the EMG power spectrum during sustained clenching at 70% and PPTs before and after the clenching in both temporalis and masseter muscles. There were no significant differences in PPT decrease between muscles or between groups during sustained clenching. There were no significant differences in maximum voluntary contraction EMG activity ratios of affected to unaffected sides between groups, or of masseter to temporalis muscles between affected and unaffected side of patients with TMJ osteoarthritis. Median frequencies decreased from the beginning to the end of the sustained clench, and the interaction between group and clench was significant: the median frequency decrease was larger in the osteoarthritis group. Our results suggested that masticatory muscles of patients with unilateral TMJ osteoarthritis are more easily fatigued during sustained clenching than normal subjects. PMID- 22672239 TI - Do proconvulsants modify or halt epileptogenesis? Pentylenetetrazole is ineffective in two rat models of temporal lobe epilepsy. AB - In patients at risk of developing epilepsy after an initial precipitating injury to the brain, the epileptogenic latent period may offer a window of opportunity for initiating potential antiepileptogenic therapy in an attempt to prevent epilepsy from developing. One potential target for antiepileptogenesis is the development of neuronal hyperexcitability during the latent period. Surprisingly, some recent studies in models of temporal lobe epilepsy (TLE) have suggested that proconvulsant drugs could have favourable effects on epileptogenesis, resulting in the proposal of pursuing proconvulsant prophylaxis for epileptogenesis. In the present study, we evaluated this provocative hypothesis by experiments with the GABA(A) receptor antagonist pentylenetetrazole (PTZ) in two TLE models, the intrahippocampal kainate model and the lithium-pilocarpine model in rats. First, we repeatedly determined the PTZ seizure threshold by i.v. infusion of the convulsant during the latent period following intrahippocampal kainate. In line with recent experiments in the lithium-pilocarpine model, the PTZ seizure threshold was significantly decreased over several days following status epilepticus. We then studied whether prolonged infusion of a proconvulsant dose of PTZ at different times after kainate or pilocarpine affected the development of epilepsy. PTZ did not prevent the development of spontaneous recurrent seizures and did not decrease their frequency or severity, but exerted only a moderate disease-modifying effect in that spontaneous seizures in the kainate model were significantly shortened. These data indicate that administration of proconvulsant drugs such as PTZ during the latent period following SE is not a promising strategy for preventing epilepsy. PMID- 22672240 TI - Effects of matrix metalloproteinase (MMP)-2 polymorphisms on responsiveness to antihypertensive therapy of women with hypertensive disorders of pregnancy. AB - Imbalanced matrix metalloproteinase (MMP) expression, including MMP-2, has been demonstrated in pre-eclampsia. However, little is known about the effect of polymorphisms in MMP-2 gene on hypertensive disorders of pregnancy. We examined whether two functional MMP-2 polymorphisms (g.-1306C>T and g.-735C>T) are associated with pre-eclampsia and/or gestational hypertension and whether these polymorphisms affect therapeutic responses in women with these conditions. We studied 216 healthy pregnant women (HP), 185 patients with gestational hypertension (GH) and 216 patients with pre-eclampsia (PE). They were stratified as responsive or non-responsive to antihypertensive therapy according to clinical and laboratorial parameters of therapeutic responsiveness. Genomic DNA was extracted from whole blood and genotypes for g-1306C>T and g.-735C>T polymorphisms were determined by real-time PCR using Taqman allele discrimination assays. Haplotype frequencies were inferred using the PHASE 2.1 program. The distributions of MMP-2 genotypes and haplotypes were similar in HP, GH and PE patients (p > 0.05). In addition, we found no significant differences in MMP-2 genotype or haplotype frequencies when GH or PE patients were classified as responsive or non-responsive to antihypertensive therapy (p > 0.05). Our results suggest that MMP-2 polymorphisms do not affect the susceptibility to hypertensive disorders of pregnancy. In parallel, MMP-2 polymorphisms apparently do not affect the responsiveness to antihypertensive therapy of women with these hypertensive disorders of pregnancy. PMID- 22672242 TI - Regarding: intradiscal pulsed radiofrequency application following provocative discography for the management of degenerative disc disease and concordant pain: a pilot study. PMID- 22672244 TI - Comment on: malignant pheochromocytoma presenting as incapacitating bony pain. PMID- 22672245 TI - Defining and applying a functionality approach to intellectual disability. AB - BACKGROUND: The current functional models of disability do not adequately incorporate significant changes of the last three decades in our understanding of human functioning, and how the human functioning construct can be applied to clinical functions, professional practices and outcomes evaluation. METHODS: The authors synthesise current literature on human functioning dimensions, systems of supports and approaches to outcomes evaluation for persons with intellectual disability (ID), and propose a functionality approach that encompasses a systems perspective towards understanding human functioning in ID. The approach includes human functioning dimensions, interactive systems of supports and human functioning outcomes. RESULTS: Based on this functionality approach the authors: (1) describe how such an approach can be applied to clinical functions related to defining ID, assessment, classification, supports planning and outcomes evaluation; and (2) discuss the impact of a functionality approach on professional practices in the field of ID. CONCLUSIONS: A functionality approach can increase focus on the integrative nature of human functioning, provide unified language, align clinical functions and encourage evidence-based practices. The approach incorporates a holistic view of human beings and their lives, and can positively affect supports provision and evaluation. PMID- 22672246 TI - Long disease duration interferes with therapeutic effect of globus pallidus internus pallidal stimulation in primary cervical dystonia. AB - OBJECTIVES: We retrospectively investigated the correlation between disease duration and the therapeutic effect of globus pallidus internus (GPi) stimulation in patients with primary cervical dystonia (CD). MATERIALS AND METHODS: Eight patients with CD unresponsive to medical treatments underwent bilateral GPi deep brain stimulation (DBS). They were followed for 63.5 +/- 38.2 months (mean +/- standard deviation) and were assessed before and at 1, 12, 24, and 36 months after surgery and at their final visit to our outpatient clinic using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Univariate analysis was performed to identify factors that affected their postoperative TWSTRS score. RESULTS: At last follow-up, disease severity and the degree of disability and pain on the TWSTRS were significantly improved by 70.2%, 76.1%, and 87.1%, respectively (p < 0.05, Wilcoxon signed-rank test). Neither age nor preoperative CD severity was predictive of postoperative improvement; however, the disease duration affected their reduction rate of TWSTRS severity score at each time point investigated (p < 0.05). CONCLUSIONS: Bilateral GPi-DBS is an effective long-term therapy in patients with CD. The delivery of GPi stimulation in the earlier course of CD may yield greater postoperative improvement. PMID- 22672247 TI - Expression of Wilms' tumor 1 (WT1) in oral squamous cell carcinoma. AB - BACKGROUND: The product of the Wilms' tumor gene, WT1 protein, is a tumor antigen for various kinds of cancer, and WT1 peptide-based cancer immunotherapy is widely anticipated as a new possibility for cancer treatment. The aim of this study was to investigate the expression of WT1 from quantitative and morphological perspectives in oral squamous cell carcinoma (OSCC), the most widespread malignant neoplasm of the oral cavity. METHODS: Six OSCC cell lines and tissue sections from 29 OSCC patients were analyzed. To detect WT1 expression, reverse transcription-polymerase chain reaction analysis (RT-PCR), real-time PCR, Western blots, and immunofluorescence flow cytometry for WT1 were performed on the cell lines, and immunohistochemistry and fluorescence in situ hybridization (FISH) were performed on the tissue sections. RESULTS: WT1 mRNA was found overexpressed in one of the six OSCC cell lines, with expression levels higher than that seen in human leukemia cell line (K562). Immunohistochemical analysis of tissue sections showed overexpression of WT1 protein in two patients, concentrated mainly in the cytoplasm of the outer one to three cell layers of the cancer nests. This was consistent with the expression of WT1 mRNA observed by FISH. Meanwhile, WT1 was not detected on normal oral epithelium. WT1 protein was detected on actively proliferating cancer nests and even on elongated epithelial ridge where new droplet-cancer-nests were being formed and starting infiltration toward subepithelial layer. CONCLUSIONS: The results suggest that WT1 plays an important role in the pathogenesis of some types of OSCC, particularly in proliferation of the cancer cells. PMID- 22672248 TI - Methotrexate vs. fumaric acid esters in moderate-to-severe chronic plaque psoriasis: data registry report on the efficacy under daily life conditions. AB - OBJECTIVE: To compare the clinical efficacy of methotrexate (MTX) vs. fumaric acid esters (FAE) in psoriasis treated under daily life conditions. METHODS: Data were extracted from a registry (http://www.psoriasisregistry.at) of 272 adult patients with moderate-to-severe chronic plaque psoriasis treated primarily with MTX (n = 72) or FAE (n = 200) between 2004 and 2011. Data from all patients, including those who did not complete at least 3 months of monotherapy, were included in an intention-to-treat (ITT) worst-case analysis. RESULTS: Thirty of 72 (41.7%) patients treated with MTX and 85 of 200 (42.5%) patients treated with FAE discontinued early, mainly due to side-effects or lack of response. Among patients who completed at least 3 months of treatment, the response to primary treatment with MTX vs. FAE did not differ significantly at any time point. In the ITT worst-case analysis at month 3, complete remission rate, PASI90, PASI75 and PASI50 rates were 6%, 7%, 24% and 39% in MTX-treated patients vs. 1%, 5%, 27% and 44% in FAE-treated patients. Overall mean PASI reduction score improved significantly in response to primary MTX and FAE treatment (by 10.6% and 12.6%, respectively) between 3 and 6 months (P = 0.0005; exact Wilcoxon test), but not between 6 and 12 months (P = 0.16). A subset of 32 patients who did not respond satisfactorily to primary treatment with FAE responded better to subsequent MTX therapy (P < 0.0001; paired Wilcoxon test). CONCLUSIONS: As shown by retrospective analysis, the primary efficacy of FAE was similar to that of MTX under daily life conditions. PMID- 22672250 TI - A tissue biopsy-based epigenetic multiplex PCR assay for prostate cancer detection. AB - BACKGROUND: PSA-directed prostate cancer screening leads to a high rate of false positive identifications and an unnecessary biopsy burden. Epigenetic biomarkers have proven useful, exhibiting frequent and abundant inactivation of tumor suppressor genes through such mechanisms. An epigenetic, multiplex PCR test for prostate cancer diagnosis could provide physicians with better tools to help their patients. Biomarkers like GSTP1, APC and RASSF1 have demonstrated involvement with prostate cancer, with the latter two genes playing prominent roles in the field effect. The epigenetic states of these genes can be used to assess the likelihood of cancer presence or absence. RESULTS: An initial test cohort of 30 prostate cancer-positive samples and 12 cancer-negative samples was used as basis for the development and optimization of an epigenetic multiplex assay based on the GSTP1, APC and RASSF1 genes, using methylation specific PCR (MSP). The effect of prostate needle core biopsy sample volume and age of formalin-fixed paraffin-embedded (FFPE) samples was evaluated on an independent follow-up cohort of 51 cancer-positive patients. Multiplexing affects copy number calculations in a consistent way per assay. Methylation ratios are therefore altered compared to the respective singleplex assays, but the correlation with patient outcome remains equivalent. In addition, tissue-biopsy samples as small as 20 MUm can be used to detect methylation in a reliable manner. The age of FFPE samples does have a negative impact on DNA quality and quantity. CONCLUSIONS: The developed multiplex assay appears functionally similar to individual singleplex assays, with the benefit of lower tissue requirements, lower cost and decreased signal variation. This assay can be applied to small biopsy specimens, down to 20 microns, widening clinical applicability. Increasing the sample volume can compensate the loss of DNA quality and quantity in older samples. PMID- 22672249 TI - Intensive care unit patients with 2009 pandemic influenza A (H1N1pdm09) virus infection - United States, 2009. AB - BACKGROUND: The influenza A (H1N1pdm09) [pH1N1] virus resulted in intensive care unit (ICU) admissions, acute respiratory distress syndrome (ARDS), and death. OBJECTIVES: To describe the characteristics of ICU patients with pH1N1 virus infection in the United States during the spring and fall of 2009 and to describe the factors associated with severe complications including ARDS and death. PATIENTS/METHODS: Through two national case-series conducted during spring and fall of 2009, medical charts were reviewed on ICU patients with laboratory confirmed pH1N1 infection by real-time reverse-transcriptase polymerase chain reaction. RESULTS: The majority (77%) of 154 patients hospitalized in an ICU were <50 years of age, and 65% had at least one underlying medical condition. One hundred and twenty-eight (83%) patients received influenza antiviral agents; 29% received treatment <= 2 days after illness onset. Forty-eight (38%) patients developed ARDS and 37 (24%) died. Patients with ARDS were more likely to be morbidly obese (36% versus 19%, P=0.04) and patients who died were less likely to have asthma (11% versus 28%, P=0.05). Compared with patients who received treatment >= 6 days after illness onset, patients treated <= 2 days after illness onset were less likely to develop ARDS (17% versus 37%, P<0.01) or die (7% versus 35%, P<0.01). CONCLUSIONS: Among patients hospitalized in an ICU with pH1N1 virus infection, ARDS was a common complication, and one-quarter of patients died. Patients with asthma had less severe outcomes. Early treatment with influenza antiviral agents was likely beneficial, especially when initiated <= 2 days after illness onset. PMID- 22672251 TI - Individual's perspective of local community environment and health indicators in older adults. AB - AIM: This study evaluated the relationship between individual's perspective of local community environment and health in older people. METHODS: A survey about quality of life in older adults in Spain was applied to a representative sample of 1106 community-dwelling people (mean age+/-SD = 72.07+/-7.83 years, 43.67% males). Local community (Community Wellbeing Index, neighborhood problems, time in the neighborhood), psychosocial and sociodemographic measures were considered. Four health outcomes (self-perceived health status, functional independence, depression and number of chronic medical conditions) were studied. Multivariate logistic analyses were carried out. RESULTS: At least two local community measures were independently associated with each health outcome. Satisfaction with community services significantly contributed to all models; it was positively related with self-rated health and functional independence, and negatively associated with depression and chronic medical conditions. CONCLUSION: The individual's perspective of the local community environment was associated with health outcomes in older adults. This can be useful in the development of policies committed to promoting social integration and active aging in the community. PMID- 22672252 TI - A high-resolution map of the Nile tilapia genome: a resource for studying cichlids and other percomorphs. AB - BACKGROUND: The Nile tilapia (Oreochromis niloticus) is the second most farmed fish species worldwide. It is also an important model for studies of fish physiology, particularly because of its broad tolerance to an array of environments. It is a good model to study evolutionary mechanisms in vertebrates, because of its close relationship to haplochromine cichlids, which have undergone rapid speciation in East Africa. The existing genomic resources for Nile tilapia include a genetic map, BAC end sequences and ESTs, but comparative genome analysis and maps of quantitative trait loci (QTL) are still limited. RESULTS: We have constructed a high-resolution radiation hybrid (RH) panel for the Nile tilapia and genotyped 1358 markers consisting of 850 genes, 82 markers corresponding to BAC end sequences, 154 microsatellites and 272 single nucleotide polymorphisms (SNPs). From these, 1296 markers could be associated in 81 RH groups, while 62 were not linked. The total size of the RH map is 34,084 cR(3500) and 937,310 kb. It covers 88% of the entire genome with an estimated inter-marker distance of 742 Kb. Mapping of microsatellites enabled integration to the genetic map. We have merged LG8 and LG24 into a single linkage group, and confirmed that LG16-LG21 are also merged. The orientation and association of RH groups to each chromosome and LG was confirmed by chromosomal in situ hybridizations (FISH) of 55 BACs. Fifty RH groups were localized on the 22 chromosomes while 31 remained small orphan groups. Synteny relationships were determined between Nile tilapia, stickleback, medaka and pufferfish. CONCLUSION: The RH map and associated FISH map provide a valuable gene-ordered resource for gene mapping and QTL studies. All genetic linkage groups with their corresponding RH groups now have a corresponding chromosome which can be identified in the karyotype. Placement of conserved segments indicated that multiple inter-chromosomal rearrangements have occurred between Nile tilapia and the other model fishes. These maps represent a valuable resource for organizing the forthcoming genome sequence of Nile tilapia, and provide a foundation for evolutionary studies of East African cichlid fishes. PMID- 22672253 TI - The Depression in Visual Impairment Trial (DEPVIT): trial design and protocol. AB - BACKGROUND: The prevalence of depression in people with a visual disability is high but screening for depression and referral for treatment is not yet an integral part of visual rehabilitation service provision. One reason for this may be that there is no good evidence about the effectiveness of treatments in this patient group. This study is the first to evaluate the effect of depression treatments on people with a visual impairment and co morbid depression. METHODS /DESIGN: The study is an exploratory, multicentre, individually randomised waiting list controlled trial. Participants will be randomised to receive Problem Solving Therapy (PST), a 'referral to the GP' requesting treatment according to the NICE's 'stepped care' recommendations or the waiting list arm of the trial. The primary outcome measure is change (from randomisation) in depressive symptoms as measured by the Beck's Depression Inventory (BDI-II) at 6 months. Secondary outcomes include change in depressive symptoms at 3 months, change in visual function as measured with the near vision subscale of the VFQ-48 and 7 item NEI VFQ at 3 and 6 months, change in generic health related quality of life (EQ5D), the costs associated with PST, estimates of incremental cost effectiveness, and recruitment rate estimation. DISCUSSION: Depression is prevalent in people with disabling visual impairment. This exploratory study will establish depression screening and referral for treatment in visual rehabilitation clinics in the UK. It will be the first to explore the efficacy of PST and the effectiveness of NICE's 'stepped care' approach to the treatment of depression in people with a visual impairment. TRIAL REGISTRATION: ISRCTN46824140. PMID- 22672255 TI - Ventricular function in patients with end-stage renal disease starting dialysis therapy: a tissue Doppler imaging study. AB - BACKGROUND: Heart failure is prevalent in end-stage renal disease (ESRD) patients on long-term dialysis. Detection of right ventricular (RV) dysfunction before starting dialysis may help to identify patients at a higher risk of developing heart failure. AIM: To assess RV function in predialysis patients using tissue Doppler imaging (TDI) derived myocardial performance index of RV (MPI-RV). METHODS: Echocardiography including pulsed TDI of lateral tricuspid annulus was performed in 41 patients with ESRD before starting dialysis therapy and 12 age and gender matched healthy controls. RV dysfunction was defined as MPI > 0.4; a value above the median MPI in controls. RESULTS: Compared to controls, ESRD patients had significantly higher blood pressure and lower hemoglobin level. MPI RV was significantly impaired in ESRD patients compared to control (0.6 vs. 0.4, P < 0.001). RV dysfunction was identified in 23 ESRD patients (56%). ESRD patients had significantly lower e' velocity and e'/a' ratio as compared with controls. Pulmonary hypertension was detected in 15 (36.5%) patients. Among ESRD patients, no correlation was detected between MPI-RV and calculated mean pulmonary artery pressure (r = -0.13, P = 0.47), pulmonary artery systolic pressure (r =-0.12, P = 0.6), left ventricular ejection fraction (r = 0.294, P = 0.06), or MPI of left ventricle (r = 0.3, P = 0.065). ESRD patients with and without pulmonary hypertension had similar MPI-RV (0.6 vs.0.62, P = 0.32). CONCLUSION: Subclinical RV dysfunction-as estimated by TDI derived MPI-is highly prevalent among ESRD patients even before starting dialysis therapy. Pulmonary hypertension is not significantly associated with RV dysfunction in these patients. PMID- 22672254 TI - The gastrointestinal electrical mapping suite (GEMS): software for analyzing and visualizing high-resolution (multi-electrode) recordings in spatiotemporal detail. AB - BACKGROUND: Gastrointestinal contractions are controlled by an underlying bioelectrical activity. High-resolution spatiotemporal electrical mapping has become an important advance for investigating gastrointestinal electrical behaviors in health and motility disorders. However, research progress has been constrained by the low efficiency of the data analysis tasks. This work introduces a new efficient software package: GEMS (Gastrointestinal Electrical Mapping Suite), for analyzing and visualizing high-resolution multi-electrode gastrointestinal mapping data in spatiotemporal detail. RESULTS: GEMS incorporates a number of new and previously validated automated analytical and visualization methods into a coherent framework coupled to an intuitive and user friendly graphical user interface. GEMS is implemented using MATLAB(r), which combines sophisticated mathematical operations and GUI compatibility. Recorded slow wave data can be filtered via a range of inbuilt techniques, efficiently analyzed via automated event-detection and cycle clustering algorithms, and high quality isochronal activation maps, velocity field maps, amplitude maps, frequency (time interval) maps and data animations can be rapidly generated. Normal and dysrhythmic activities can be analyzed, including initiation and conduction abnormalities. The software is distributed free to academics via a community user website and forum (http://sites.google.com/site/gimappingsuite). CONCLUSIONS: This software allows for the rapid analysis and generation of critical results from gastrointestinal high-resolution electrical mapping data, including quantitative analysis and graphical outputs for qualitative analysis. The software is designed to be used by non-experts in data and signal processing, and is intended to be used by clinical researchers as well as physiologists and bioengineers. The use and distribution of this software package will greatly accelerate efforts to improve the understanding of the causes and clinical consequences of gastrointestinal electrical disorders, through high-resolution electrical mapping. PMID- 22672256 TI - Quality of life in patients with acne in Erbil city. AB - BACKGROUND: Acne is a very common condition and has a substantial impact on patients' quality of life. This study was carried out to determine the impact of acne and its clinical severity on health related quality of life in a group of patients attending private clinic in Erbil city, Iraq. METHODS: A cross-sectional study was conducted between July 1st, 2011 and November 1st, 2011. A convenience sample of 510 patients attending private clinic in Erbil city was taken. Verbal informed consent was obtained from all participants. The Cardiff acne disability index (CADI) was used in this study. RESULTS: The sample included 510 patients (173 males and 337 females); their mean +/- SD age was 20.08 +/- 4.23 years (ranged from 11 to 36 years) with a male: female ratio of 0.41:1. The mean +/- SD ages of males and females were 18.62 +/- 3.19 and 20.83 +/- 4.49 years, respectively (P < 0.001). Results revealed that there is significant association between age and quality of life impairment (P < 0.001), and it revealed that quality of life was more impaired (47.2%) among female than that (37.6%) among male patients (P = 0.038). There was significant association between grading of acne and QOL impairment (P < 0.0001). CONCLUSIONS: Acne negatively affects quality of life, females were more affected than the males, age group 21-25 more than the other age groups and the greater the grade "severity" of acne, the greater the level of impairment of quality of life. PMID- 22672257 TI - Clinical evaluation of a new device in the assessment of peripheral sensory neuropathy in diabetes. AB - AIMS: Current National Institute for Health and Clinical Excellence guidelines state that patients with diabetes should have annual examination of their feet to exclude signs of sensory impairment. The VibraTip is a new disposable device producing a vibratory stimulus, which has been developed in order to screen for peripheral sensory neuropathy in diabetes. This study was designed to evaluate the device by assessing intra-rater reliability and comparing the ability of the VibraTip to detect or exclude peripheral sensory neuropathy with other bedside methods. METHODS: One hundred and forty-one patients with diabetes (Type 1 or Type 2) were examined for diabetic peripheral sensory neuropathy using a Neurothesiometer, 10-g monofilament, a 128-Hz tuning fork, a NeurotipTM and a VibraTip. The failure to perceive the Neurosthesiometer stimulus at >= 25 V in either foot was considered the reference method for the presence of peripheral sensory neuropathy. Receiver operating characteristic curves were produced for each device and the sensitivity, specificity, predictive values and likelihood ratios for the diagnosis of peripheral sensory neuropathy were calculated. Repeat testing with the VibraTip was performed in 18 patients and intra-rater reliability assessed using Cronbach alpha. RESULTS: Analysis of the area under the receiver operating characteristic curves showed that the 10-g monofilament was significantly better than the 128-Hz tuning fork (P = 0.0056) and the Neurotip (P = 0.0022), but was no different from the VibraTip (P = 0.3214). The alpha coefficient for the VibraTip was calculated to be 0.882, indicating good reliability. CONCLUSIONS: The VibraTip is a device comparable with the 10-g monofilament and therefore could be considered a useful tool for screening for peripheral sensory neuropathy in diabetes. PMID- 22672258 TI - Polymorphic miRNA-mediated gene contribution to inhibitor development in haemophilia A. AB - Development of inhibitory antibodies is perhaps the most serious complication of FVIII replacement therapy, precluding efficient clinical management of patients with haemophilia A (HA). The development and function of immune system are also regulated by microRNAs (miRNAs). Mutations and changes in the level of expression of some miRNA genes have been associated with the onset and progression of immunological disorders. The aim of this study was to investigate new genetic polymorphisms in loci for miRNA and their targets to evaluate whether these SNPs may confer susceptibility to inhibitor development in patients with HA. Italian HA patients with and without inhibitors and healthy controls were recruited in this study. For SNP analysis, standard DNA sequencing method was used. We have studied four SNPs, i.e. rs36101366, rs34683807, rs1803603 and rs3024496 located in the 3'UTR of F8 and IL-10 genes. These SNPs have been checked for their frequencies in patients with and without inhibitors, but no statistically significant differences were found. Then, we have searched for other genetic variants in loci for haematopoietic-specific miRNAs, i.e. hsa-mir-150, hsa-mir 155, hsa-mir-146a, hsa-mir-142, hsa-mir-181a and in a specific miRNA, hsa-mir 1184, i.e. predicted to be located in the intron 22 of F8 gene. For all miRNAs selected, we did not identify any sequence variation in our study population. This is the first study to demonstrate that there was no association between selected SNPs in miRNAs and their targets and the susceptibility to inhibitor development in people affected by HA. PMID- 22672259 TI - Serum concentrations of vascular endothelial growth factor in an infant treated with ranibizumab for retinopathy of prematurity. PMID- 22672260 TI - Hepcidin and erythropoietin measurements in the cord blood of neonates with meconium-stained amniotic fluid. AB - AIM: To compare hepcidin and erythropoietin levels in the cord blood of neonates with meconium-stained amniotic fluid (MSAF) to levels obtained from age-, body mass index- and gravidity-matched neonates with clear amniotic fluid. METHODS: A cross-sectional controlled study was conducted in secondary and tertiary care centers. Cord blood samples of 40 neonates following term gestations (>=37 weeks' gestation) with MSAF and 40 maternal age-, body mass index- and gravidity-matched controls with clear amniotic fluid were analyzed in this study. Demographic data, delivery outcomes and laboratory evaluations were recorded. RESULTS: Cord blood pH levels were lower in fetuses with MSAF when compared to those with clear amniotic fluid (P=0.0001). Fetuses with MSAF had higher cord blood erythropoietin levels in comparison to those with clear amniotic fluid (P=0.0001). Delivery outcomes and hepcidin measurements were similar in both groups. CONCLUSIONS: We demonstrated a significant relationship between erythropoietin levels and meconium passage, but failed to show the existence of a relationship between hepcidin levels and meconium passage. PMID- 22672261 TI - Rhizosphere fungus Penicillium chrysogenum promotes growth and induces defence related genes and downy mildew disease resistance in pearl millet. AB - Susceptible pearl millet seeds (cv 7042S) were treated with the plant growth promoting fungus Penicillium chrysogenum (PenC-JSB9) at 1 * 10(8) spores.ml(-1) to examine mRNA expression profiles of five defence responsive genes and test its ability to induce resistance to downy mildew caused by Sclerospora graminicola. PenC-JSB9 treatment at 1 * 10(8) CFU.ml(-1) for 6 h significantly enhanced seed germination (9.8- 89%), root length (4.08% to 5.1 cm), shoot length (18.9% to 7.77 cm) and reduced disease incidence (28%) in comparison with untreated controls. In planta colonisation of PenC-JSB9 showed that all three root segments (0-6 cm) and soil dilutions incubated on PDA produced extensive mycelial growth, however colonisation frequency of PenC-JSB9 was significantly higher in soil than in root segments. Spatiotemporal studies revealed that induction of resistance was triggered as early as 24 h and a minimum 2-3 days was optimal for total resistance to build up between inducer treatment and challenge inoculation in both experiments. In Northern blot analysis, transcript accumulation of resistant and PenC-JSB9 induced susceptible cultivars showed higher basal levels of defence gene expression than non-pretreated susceptible controls. Transcript accumulation in resistant seedlings challenge-inoculated with the pathogen showed maximum expression of CHS (3.5-fold increase) and Pr-1a (threefold increase) at 24 and 12 h, respectively. While PenC-JSB9 pretreated susceptible seedlings challenge inoculated showed rapid and enhanced expression of LOX and POX at 48 h and for CHT at 24 h, whereas non-pretreated susceptible seedlings after pathogen inoculation showed weak expression of hybridised defence genes. Enhanced activation of defence genes by PenC-JSB9 suggests its role in elevated resistance against S. graminicola. PMID- 22672262 TI - Antibodies to the glutamate receptor in mania. AB - BACKGROUND: There is evidence that the glutamatergic system is involved in the pathophysiology of mania. Antibodies to the NR2 subunits of the N-methyl-D aspartate (NMDA) receptor have been shown to adversely affect glutamate functioning. METHODS: We measured serum antibodies to the NR2 peptide of the NMDA receptor in 60 individuals with different subtypes of mania, including schizoaffective cases, who were assessed at up to three time points. We also measured these antibodies in 295 individuals in other psychiatric groups and in 170 non-psychiatric controls. NR2 antibody levels were compared among groups by multivariate analyses and within the mania group by repeated measures analysis of variance. RESULTS: Individuals with mania had increased levels of antibodies to the NR2 peptide compared to levels in non-psychiatric controls when measured at the time of admission (t = 2.99, p = 0.003) and the time of evaluation (t = 2.57, p = 0.010), but not at follow-up six months later. The levels of antibodies in individuals in other psychiatric groups did not differ significantly from the levels measured in the control population. Within the mania group, there was a significant decrease in antibody levels over the three time points of the study (F = 5.4, df = 2, p = 0.0067). CONCLUSIONS: NR2 antibodies are elevated during the acute phase of mania but not at follow-up. Our findings support a role for antibodies to the NMDA receptor in the pathogenesis of acute mania. PMID- 22672263 TI - Novel hydrophilic docetaxel (CQMU-0519) analogue inhibits proliferation and induces apoptosis in human A549 lung, SKVO3 ovarian and MCF7 breast carcinoma cell lines. AB - OBJECTIVE: Objectives of this investigation were not merely to perform a comparative study with original docetaxel, but to define anti-proliferative and apoptotic effects of novel hydrophilic docetaxel (CQMU-0519) analogue on A549 lung, SKVO3 ovary and MCF7 breast carcinoma cell lines. MATERIALS AND METHODS: The materials for the study consist of a completely new docetaxel analogue (CQMU 0519), synthesized by the Department of Pharmacology, Chongqing Medical University, China, which is completely soluble in water. 50 nm of drug concentration was utilized on all three cell lines where cell population growth was assessed using cell culture kit-8 and flow cytometry analysis, whereas apoptotic pathways were unveiled by use of annexin-V FITC, apoptosis DNA ladder, caspases-3, 6, 8 and 9; in the meanwhile, regulation of Bcl-2 family members was analysed by western blotting. RESULT: The novel docetaxel analogue (CQMU-0519) suppressed cell proliferation in all three cell lines, inhibition of cell proliferation and cell cycle arrest being more evident in G(2) /M phase. Also, in both lung and ovarian cell lines, apoptotic levels were higher as measured by the various tests performed, and downregulation of Bcl-2 and Bcl-xL with increased expressions of Bad and Bax indicated the intrinsic pathway for apoptosis. Nevertheless, it was found that MCF7 cells, although also manifesting high levels of apoptosis, used the extrinsic pathway instead. Hence, it was shown that novel docetaxel analogue (CQMU-0519) may have some prospective use in future clinical trials. CONCLUSIONS: Novel hydrophilic docetaxel analogue (CQMU-0519) inhibited cell proliferation and enhanced the intrinsic apoptotic pathway in lung and ovarian carcinoma cells, whereas it used the extrinsic one in breast adenocarcinoma cells. PMID- 22672265 TI - Assessment of replication rates of human keratinocytes in engineered skin substitutes grafted to athymic mice. AB - Stable closure of skin wounds with engineered skin substitutes (ESS) requires indefinite mitotic capacity to generate the epidermis. To evaluate whether keratinocytes in ESS exhibit the stem cell phenotype of label retention, ESS (n = 6-9/group) were pulsed with 5-bromo-2'-deoxyuridine (BrdU) in vitro, and after grafting to athymic mice (n = 3-6/group). Pulse and immediate chase in vitro labeled virtually all basal keratinocytes at day 8, with label uptake decreasing until day 22. Label retention in serial chase decreased more rapidly from day 8 to day 22, with a reorganization of BrdU-positive cells into clusters. Similarly, serial chase of labeled basal keratinocytes in vivo decreased sharply from day 20 to day 48 after grafting. Label uptake was assessed by immediate chases of basal keratinocytes, and decreased gradually to day 126, while total labeled cells remained relatively unchanged. These results demonstrate differential rates of label uptake and retention in basal keratinocytes of ESS in vitro and in vivo, and a proliferative phenotype with potential for long-term replication in the absence of hair follicles. Regulation of a proliferative phenotype in keratinocytes of ESS may improve the biological homology of tissue-engineered skin to natural skin, and contribute to more rapid and stable wound healing. PMID- 22672266 TI - Has the DRG system impacted on inpatient allergy care in university dermatology departments in Germany? AB - BACKGROUND: Diagnostic provocation tests (ICD Z01.5) have a low cost weight in the German DRG system. We aimed at investigating a possible economic impact on the number of provocation tests in German university medical centers (UMC) for dermatology. METHODS: We review quality records of 35 German UMC for 2008 and 2010 (ICD Z01.5, total number of patients as well as priority ranking). RESULTS: 33/35 hospitals gave full data for both years including the ten most frequent diagnoses. Between 2008 and 2010, total number of patients treated increased in 23/33 (70 %) UMC, those with ICD Z01.5 only in 11/24 (46 %) UMC with full data. In 2008, the ICD Z01.5 was in the top ten list of main diagnoses in 29/33 (88 %) hospitals, in 2010 in 25/33 (76 %); also, priority ranking tended to decrease. In contrast, total number of ICD Z01.5 in Germany tended to increase slightly. CONCLUSIONS: We noticed a tendency for decreasing numbers of provocation tests being performed in dermatological UMC in Germany. As there is no evidence for a decreasing number of patients suffering from allergies, one may speculate about a shift to non-university departments due to an economic impact. PMID- 22672264 TI - Host HDL biogenesis machinery is recruited to the inclusion of Chlamydia trachomatis-infected cells and regulates chlamydial growth. AB - Chlamydia trachomatis is an obligate intracellular bacterial pathogen that is the most common cause of sexually transmitted bacterial infections and is the etiological agent of trachoma, the leading cause of preventable blindness. The organism infects epithelial cells of the genital tract and eyelid resulting in a damaging inflammatory response. Chlamydia trachomatis grows within a vacuole termed the inclusion, and its growth depends on numerous host factors, including lipids. Although a variety of mechanisms are involved in the acquisition of host cell cholesterol and glycosphingolipids by C. trachomatis, none of the previously documented pathways for lipid acquisition are absolutely required for growth. Here we demonstrate that multiple components of the host high-density lipoprotein (HDL) biogenesis machinery including the lipid effluxers, ABCA1 and CLA 1, and their extracellular lipid acceptor, apoA-1, are recruited to the inclusion of C. trachomatis-infected cells. Furthermore, the apoA-1 that accumulates within the inclusion colocalizes with pools of phosphatidylcholine. Knockdown of ABCA1, which mediates the cellular efflux of cholesterol and phospholipids to initiate the formation of HDL in the serum, prevents the growth of C. trachomatis in infected HeLa cells. In addition, drugs that inhibit the lipid transport activities of ABCA1 and CLA 1 also inhibit the recruitment of phospholipids to the inclusion and prevent chlamydial growth.These results strongly suggest that C. trachomatis co-opts the host cell lipid transport system involved in the formation of HDL to acquire lipids, such as phosphatidylcholine, that are necessary for growth. PMID- 22672267 TI - Effect of veneering technique on the fracture resistance of zirconia fixed dental prostheses. AB - To compare the fracture resistance of zirconia 3-unit posterior fixed dental prostheses (FDPs) frameworks veneered with different veneering materials and techniques before and after artificial ageing. Forty-eight zirconia 3-unit FDPs, representing a missing first molar, were adhesively cemented on human teeth. The zirconia frameworks were randomly distributed according to the veneering materials and techniques into three groups, each containing 16 samples: group LV (layering technique/Vintage ZR), group LZ (layering technique/ZIROX) and group PP (CAD/CAM and press-over techniques/PressXZr). Half of each group was artificially aged through dynamic loading and thermocycling to simulate 5 years of clinical service. Afterwards, all specimens were tested for fracture resistance using compressive load. An analysis of variance (anova) was used to assess the effect of veneering ceramic and artificial ageing on fracture resistance (P < 0.05). Except for one minor cohesive chipping in group LV1, all specimens survived artificial ageing. The mean fracture resistance values (in Newton) of different non-aged (+/- s.d.)/aged (+/- s.d.) groups were as follows: LV0 2034 (+/- 401)/LV1 1625 (+/- 291); LZ0 2373 (+/- 718)/LZ1 1769 (+/- 136); and PP0 1959 (+/- 453)/PP1 1897 (+/- 329). Artificial ageing significantly reduced the fracture resistance in groups veneered with the layering technique (P < 0.05), whereas no significant effect was found in specimens veneered with the CAD/CAM and press over techniques. All tested systems have the potential to withstand occlusal forces applied in the posterior region. The combination of the CAD/CAM and press over techniques for the veneering process improved the overall stability after artificial ageing, relative to the layering technique. PMID- 22672268 TI - Early-life stress-induced anxiety-related behavior in adult mice partially requires forebrain corticotropin-releasing hormone receptor 1. AB - Early-life stress may lead to persistent changes in central corticotropin releasing hormone (CRH) and the CRH receptor 1 (CRHR1) system that modulates anxiety-related behavior. However, it remains unknown whether CRH-CRHR1 signaling is involved in early-life stress-induced anxiety-related behavior in adult animals. In the present study, we used conditional forebrain CRHR1 knockout (CRHR1-CKO) mice and examined the potential role of forebrain CRHR1 in the anxiogenic effects of early-life stress. As adults, wild-type mice that received unstable maternal care during the first postnatal week showed reduced body weight gain and increased anxiety levels in the open field test, which were prevented in stressed CRHR1-CKO mice. In the light-dark box test, control CRHR1-CKO mice were less anxious, but early-life stress increased anxiety levels in both wild-type and CRHR1-CKO mice. In the elevated plus maze test, early-life stress had only subtle effects on anxiety-related behavior. Moreover, early-life stress did not alter the basal home cage activity and gene expression levels of key hypothalamic pituitary-adrenal axis regulators in adult wild-type and CRHR1-CKO mice, but enhanced neuroendocrine reactivity to acute immobilization stress in CRHR1-CKO mice. Our findings highlight the importance of forebrain CRHR1 in modulating some of the anxiogenic effects of early-life stress, and suggest that other neural circuits are also involved in the programming effects of early-life stress on anxiety-related behavior. PMID- 22672269 TI - Heparin affin regulatory peptide modulates the endogenous anticoagulant activity of heparin and heparan sulphate mimetics. AB - Pleiotrophin, also known as heparin affin regulatory peptide (HARP), is a growth factor expressed in various tissues and cell lines. In this work, HARP was tested for its capacity to modulate the anticoagulant activity of heparin and heparan sulphate mimetics (OTR4120). We used both in vitro and in vivo assays. HARP was found to be differently effective for neutralization of the anticoagulant activity of the mimetic heparan sulphate (OTR4120) and heparin in purified system and human plasma. HARP was shown to compete with both antithrombin and thrombin for binding to heparin and to OTR4120, respectively. In the presence of OTR4120, the V(max) was constant and the calculated maximum velocity was 1.56 U/min; the thrombin Km value (0.011 nM) was affected by HARP concentrations. The Km (HARP) value was 0.085 nM, which is consistent with high affinity of HARP to OTR4120. Under the same conditions, initial velocity patterns for antithrombin-heparin were determined in the presence or in the absence of HARP. The antithrombin value Km (0.022 nM) was affected by HARP (0.077 nM). HARP exhibits efficacy equivalent to or greater than protamine. Interestingly, intraperitoneally administered HARP decreased the anticoagulant activity of heparin and of OTR4120 in mice. Taken together, these data provide the first evidence for a physiological role of HARP in the modulation of anticoagulant activity of heparin and heparin-like material. PMID- 22672270 TI - Siblings of individuals with Smith-Magenis syndrome: an investigation of the correlates of positive and negative behavioural traits. AB - BACKGROUND: Smith-Magenis syndrome (SMS) is a neurodevelopmental disorder that affects approximately one out of 25,000 births worldwide. To date, no research has been conducted to investigate how having an individual with SMS in a family is a positive or negative influence on siblings. METHODS: To investigate this question we conducted a study involving 79 siblings and 60 parents of individuals with SMS to assess perceptions of how having a sibling with SMS positively and negative influence siblings' behavioural traits. RESULTS: Our findings show that age of siblings of individuals with SMS was associated with a significant increase in positive behavioural traits and a significant decrease in negative behavioural traits. Additionally, siblings who perceive benefits from having a sibling with SMS demonstrate significantly more positive behavioural traits and significantly fewer negative behavioural traits. Parents accurately assess the changes in sibling behavioural traits with age, and parents who perceive their child as having experienced benefits from the sibling relationship report that siblings demonstrate significantly more positive behavioural traits and significantly fewer negative behavioural traits. CONCLUSIONS: Our research shows that although individuals experience difficulties as a result of having a sibling with SMS, overall, siblings tend to fare well and parents appreciate both the positive and negative behavioural effects that result from having a sibling with SMS. PMID- 22672271 TI - Examining the science of aging. PMID- 22672272 TI - Hyaluronic acid plus mannitol treatment for improved skin hydration and elasticity. AB - BACKGROUND: Mesotherapy treatment of aging skin aims to replace depleting levels of minerals, vitamins, amino acids, and hyaluronic acid (HA). AIM: To investigate the efficacy of 13.5 mg/g uncross-linked HA+0.9% mannitol (HA+mannitol) on skin hydration and elasticity. PATIENTS/METHODS: Four centers enrolled 34 women: Subgroup 1 comprised 27 subjects injected using a "depot" technique; Subgroup 2 comprised seven subjects injected using a "picotage" technique. RESULTS: A notable difference was seen between the two subgroups in outcome and subject satisfaction. In Subgroup 1, a significant improvement was seen in hydration, anisotropy, and skin roughness, but Subgroup 2 showed no significant improvements. Most physicians assessed HA+mannitol as "easy/very easy" to inject. Physician esthetic assessment in Subgroup 1 was "improved/very improved" for >90% of subjects at Day 60, and >80% according to subject assessment. 95% of subjects were delighted with treatment, and 85% would undergo repeat treatment and would recommend treatment to a friend. However, results for Subgroup 2 indicated 86% of subjects were unhappy with treatment and 83% would refuse to undergo repeat treatment. CONCLUSIONS: HA+mannitol is effective for skin hydration, anisotropy, and roughness when treated using a depot technique. PMID- 22672273 TI - Long-term aesthetic outcomes with injectable poly-l-lactic acid: observations and practical recommendations based on clinical experience over 5 years. AB - BACKGROUND: Facial rejuvenation techniques have evolved in recent decades driven by a paradigm shift to restoration of lost volume, and an increase in the number of available products. As clinical experience has increased, practitioners have further refined the use of these products. OBJECTIVES: To share observations and practical recommendations based on clinical experience with the aesthetic use of injectable poly-l-lactic acid (PLLA) in patients followed for up to 5 years. METHODS: Literature review and retrospective case history review of the first 100 patients treated with injectable PLLA, many of whom have been followed for over 5 years. RESULTS: Use of injectable PLLA, alone or in combination with other products, has provided excellent and long-lasting (up to 5 years) aesthetic results for most of the reviewed patients. Typically, patients have received one or two touch-up sessions between years 2 and 4 after initial full correction. There were minimal adverse events of papule formation; these eventually resolved. CONCLUSIONS: Injectable PLLA is a safe and effective option for achieving long term patient satisfaction with soft-tissue augmentation. PMID- 22672274 TI - Formulation optimization, skin irritation, and efficacy characterization of a novel skin-lightening agent. AB - BACKGROUND: Skin-lightening preparations are used by people all over the world for a diverse range of dermatologic indications. The gold standard treatment for skin lightening is with hydroquinone but has been controversial because of the presence of several side effects. Therefore, there has been a constant search for developing new treatment alternatives. Furthermore, the new amendments and bans on animal testing by ECVAM have made the three-dimensional models like EpiDerm(TM) and MelanoDerm(TM) increasingly popular. OBJECTIVE: This work aims at the formulation development for a new skin-lightening agent, SMA-012, followed by testing for skin irritation and efficacy. METHODS: Formulation parameters such as concentration of SMA-012, amount of ethanol, effect of permeation enhancers and pH were first optimized using Franz cell experiments. Tape stripping and underlying skin assays were performed to analyze the amounts of SMA-012 in different layers of skin. The irritation potential and efficacy of the screened formulation were evaluated using Epiderm(TM) and Melanoderm(TM) models. RESULTS: Skin permeation experiments suggested that concentrations of 0.1% SMA-012, 35% ethanol, and pH of 8.5 to be the best formulation characteristics. This particular formulation was found to be nonirritant for short-term exposure, when tested in Epiderm(TM) model and also significantly effective in decreasing the amount of melanin in pigmented skin equivalent models. CONCLUSION: SMA-012 shows a good promise as a skin-lightening agent for cosmetic and therapeutic applications. Additionally, our study demonstrates the application of skin equivalent models as alternatives to animal testing in studying the regulation of skin pigmentation. PMID- 22672275 TI - Skin presenting a higher level of caspase-14 is better protected from UVB irradiation according to in vitro and in vivo studies. AB - Caspase-14, a cysteine endoproteinase belonging to the conserved family of aspartate-specific proteinases, was shown to play an important role in the terminal differentiation of keratinocytes and barrier function of the skin. In the present study, we developed a biofunctional compound that we described as a modulator of caspase-14 expression. Using normal human keratinocytes (NHK) in culture and human skin biopsies, this compound was shown to increase caspase-14 expression and partially reverse the effect of caspase-14-specific siRNA on NHK. Moreover, the increase in filaggrin expression visualized on skin biopsies and the recovery of the barrier structure after tape-stripping indicated that this compound could exhibit a beneficial effect on the skin barrier function. Considering the possible link between caspase-14 and the barrier function, a UVB irradiation on NHK and skin biopsies previously treated with the caspase-14 inducer, was performed. Results indicated that pretreated skin biopsies exhibited less signs of UV damage such as active caspase-3 and cyclobutane pyrimidine dimers (CPDs). Likewise, pretreated NHK were protected from UV-induced genomic DNA damage, as revealed by the Comet Assay. Finally, a clinical test showed a reduction of transepidermal water loss (TEWL) on the treated skin compared with placebo, under UV stress condition, confirming a protecting effect. Taken together, these results strongly suggest that, by increasing caspase-14 expression, the biofunctional compound could exhibit a protective effect on the skin barrier function, especially in case of barrier damage and UV irradiation. PMID- 22672277 TI - Problems in pattern alopecia. AB - Female pattern hair loss (FPHL) was originally described as synonymous with androgenetic alopecia. However, the role of androgens in FPHL has not been proven, and the etiology is not yet defined. Several patterns of hair loss in women have been described, in addition to descriptions of scarring alopecias mimicking FPHL. In this paper, we discuss FPHL as an entity other than androgenetic alopecia and suggest that de-emphasizing the physicians reliance on pattern in the diagnosis of hair loss in women, and instead utilizing other tools including dermoscopy and histopathology, would benefit clinician's efforts in treating alopecias. PMID- 22672276 TI - Multiple minimally invasive Erbium: Yttrium Aluminum Garnet laser mini-peels for skin rejuvenation: an objective assessment. AB - BACKGROUND: As the demand for minimally invasive rejuvenation is increasing, micropeel resurfacing using Erbium:Yttrium Aluminum Garnet (Er:YAG) laser 2940 nm has been reported for the treatment of photoaged skin without ablation of the epidermis. However, little is known about the efficacy and underlying histologic changes associated with this type of treatment. AIMS: The aims of this study are to evaluate the clinical effect and objectively quantify the histological changes in response to multiple sessions of Er:YAG laser 2940 nm mini-peels. PATIENTS AND METHODS: Six female volunteers of Fitzpatrick skin type III-IV and Glogau's class I-III wrinkles were subjected to six microresurfacing peels at 2-week intervals using Er:YAG 2940 nm laser at subablative fluences of 2-3 J/cm(2) to treat periorbital rhytides. Quantitative evaluation of collagen types I, III, and VII, newly synthesized collagen, total elastin, and tropoelastin was performed by histochemistry and immunohistochemistry coupled with computerized morphometric analysis at base line, end of treatment, and 3 months post-treatment. RESULTS: Compared to the base line, evaluation of volunteers revealed obvious clinical improvement in response to Er:YAG mini-peels. Collagen types I, III, and VII, as well as newly synthesized collagen, together with tropoelastin showed a statistically significant increase in response to treatment, while the mean level of total elastin was significantly decreased in response to treatment. However, this was followed by regression of improvement at 3 months post-treatment but was still better than baseline. CONCLUSIONS: This study revealed that multiple Er:YAG mini-peels is a promising treatment option for photoaging as it reverses the signs of photoaged skin with little downtime and side effects. However, to maintain the short-term improvement achieved after treatment, continued Er:YAG 2940 nm laser mini-peels is required. PMID- 22672278 TI - Effects of solar radiation on the skin. AB - No one would underestimate the importance of sunlight to the evolution of life on the earth and its role in human development. However, all humans - especially individuals who are lightly pigmented or whose occupation or lifestyle exposes them to excessive amounts of sunlight - are potentially susceptible to its deleterious effects. These effects can range from acute biological responses, such as sunburn and skin tanning, to conditions resulting from chronic exposure such as photoaged skin and potentially life-threatening conditions such as skin cancer. The objective of this review is to present a concise and up-to-date perspective on the effects of UVB, UVA, visible, and infrared radiation on cutaneous biochemistry and physiology. PMID- 22672279 TI - Subcision for treatment of rolling acne scars in Iraqi patients: a clinical study. AB - BACKGROUND: Acne scarring is a common dermatologic problem causing a great cosmetic disfigurement. Subcision is one of the effective modalities for treatment of rolling acne scars. OBJECTIVE: To evaluate the efficacy and safety of subcision for rolling acne scars in Iraqi patients. PATIENTS AND METHODS: Forty patients (21 males and 19 females) with moderate to severe grades of facial rolling acne scars were enrolled in this study. Subcision was done for all patients. Patients were followed up at 2, 6, 12 weeks, and 6 months after the last session. The response to treatment was evaluated by objective and subjective methods. RESULTS: Thirty-four patients completed the study and follow up period. Eight of them were complaining of severe and 26 of moderate grade of acne scars. At the end of the study, 18 (52.94%) patients had mild grade, 15 (44.11%) patients had moderate grade, and one (2.92%) patient had severe grade. This change was statistically highly significant (P-value = 0.0000001). The average scar score before treatment was 13.264 +/- 1.675; and it improved to 9.47 +/- 2.71 after 6 months (P-value = 0.0000001). Regarding the photographic assessment, the difference in the visual analogue scale before and after the treatment was statistically highly significant (P-value = 0.0000001). All patients were satisfied regarding the improvement after treatment with varying degrees. All reported side-effects were mild and transient. CONCLUSION: Subcision is a safe, easy to perform, well-tolerated, and valuable surgical technique for treatment of rolling acne scars. PMID- 22672280 TI - Melasma in men. AB - Melasma is an acquired hypermelanosis that results in localized hyperpigmentation, commonly found on the face. This condition is much more common in women than men. There are some features of melasma in men that seem to differ from those seen in women. However, there is a paucity of data on this topic. The aim of this article is to review the etiology, clinical presentation, and treatment of melasma in men. It is important for dermatologists to understand some unique aspects of melasma in this group to provide appropriate care for patients who suffer from this frustrating condition. PMID- 22672281 TI - Hair transplant for acne scars: an innovative approach. AB - Postacne scarring is a common entity that affects patients both physically and psychologically. Treatment of facial scarring is rarely a mono-dimensional process. Various modalities of treatments from cheaper subcision, punch techniques and excision to expensive laser resurfacing techniques are available. Treatment of postacne scars in a particular case has to be individualized, taking into consideration many factors like age, gender, types of scarring, Fitzpatrick skin type, and socioeconomic status of the patient. In this article, we describe an innovative method of simply doing hair transplantation in acne scars and hence making them less visible and cosmetically well acceptable to the patient. PMID- 22672282 TI - Modulation of telomere binding proteins: a future area of research for skin protection and anti-aging target. AB - Telomere shortening is considered as one of the main characteristics of cellular aging by limiting cellular division. Besides the fundamental advances through the discoveries of telomere and telomerase, which were recognized by a Nobel Prize, telomere protection remains an essential area of research. Recently, it was evidenced that studying the cross-talks between the proteins associated with telomere should provide a better understanding of the mechanistic basis for telomere-associated aging phenotypes. In this review, we discuss the current knowledge on telomere shortening, telomerase activity, and the essential role of telomere binding proteins in telomere stabilization and telomere-end protection. This review highlights the capacity of telomere binding proteins to limit cellular senescence and to maintain skin tissue homeostasis, which is of key importance to reduce accelerated tissue aging. Future studies addressing telomere protection and limitation of DNA damage response in human skin should include investigations on telomere binding proteins. As little is known about the expression of telomere binding proteins in human skin and modulation of their expression with aging, it remains an interesting field of skin research and a key area for future skin protection and anti-aging developments. PMID- 22672283 TI - Terminology matters: patient understanding of "opioids" and "narcotics". AB - BACKGROUND: The terms "opioid" and "narcotic" are often used interchangeably by healthcare providers. The purpose of this study was to compare understanding "narcotics" vs. "opioids." METHODS: A convenience sample of English-speaking women (n = 188), aged 21-45 years, seeking care at a primary care clinic were asked (1) "What is an opioid/narcotic?" (2) "Give an example of an opioid/narcotic?" (3) "Why does someone take an opioid/narcotic?" and (4) "What happens when someone takes an opioid/narcotic for a long time?" Responses were recorded verbatim by a research assistant and then coded independently by two investigators. RESULTS: More than half of respondents (55.9%) responded "don't know" to all 4 opioid questions, while just 3.2% responded "don't know" to all 4 narcotic questions (P < 0.01). Most women were unfamiliar with the term opioid (76.3%) and did not know why someone would take an opioid (68.8%). About two thirds of respondents were able to give an example of a narcotic (64.2%) and knew the consequences of long-term narcotic use (63.2%). CONCLUSIONS: While more women were more familiar with narcotic, many identified negative connotations with this term. Future research should explore how to improve patient understanding and attitudes regarding both the terms opioids and narcotics. PMID- 22672284 TI - Can procalcitonin tests aid in identifying bacterial infections associated with influenza pneumonia? A systematic review and meta-analysis. AB - OBJECTIVE: To summarize evidence for the diagnostic accuracy of procalcitonin (PCT) tests for identifying secondary bacterial infections in patients with influenza. METHODS: Major databases, including MEDLINE, EMBASE, and the Cochrane Library, were searched for studies published between January 1966 and May 2009 that evaluated PCT as a marker for diagnosing bacterial infections in patients with influenza infections and that provided sufficient data to construct two-by two tables. RESULTS: Six studies were selected that included 137 cases with bacterial coinfection and 381 cases without coinfection. The area under a summary ROC curve was 0.68 (95% CI: 0.64-0.72). The overall sensitivity and specificity estimates for PCT tests were 0.84 (95% CI: 0.75-0.90) and 0.64 (95% CI: 0.58 0.69), respectively. These studies reported heterogeneous sensitivity estimates ranging from 0.74 to 1.0. The positive likelihood ratio for PCT (LR+ = 2.31; 95% CI: 1.93-2.78) was not sufficiently high for its use as a rule-in diagnostic tool, while its negative likelihood ratio was reasonably low for its use as a rule-out diagnostic tool (LR- = 0.26; 95% CI: 0.17-0.40). CONCLUSIONS: Procalcitonin tests have a high sensitivity, particularly for ICU patients, but a low specificity for identifying secondary bacterial infections among patients with influenza. Because of its suboptimal positive likelihood ratio and good negative likelihood ratio, it can be used as a suitable rule-out test but cannot be used as a standalone rule-in test. PMID- 22672285 TI - Does sacral neuromodulation lead to relevant reduction in the need for intermittent catheterization? A single-center experience on patients with chronic urinary retention. AB - PURPOSE: Sacral neuromodulation (SNM) is an approved method for second-line treatment of different therapy refractory disorders of the urinary bladder. Alongside success in overactive bladder symptoms for detrusor overactivity, SNM also was shown to succeed in chronic urinary retention (UR) of various etiology. METHODS: From October 2007 to December 2010, a cohort of 20 patients received two-stage InterStim tined-lead(r) (Medtronic Inc., Minneapolis, MN, USA) SNM therapy for UR. The number of electrodes implanted was decided by surgeons on the basis of patients' clinical presentation and extent of UR. Dependent on the treatment success, patients received either implantation of the implantable pulse generator (IPG) or the electrodes were removed. Median follow-up time was 12 months (1-38 months). RESULTS: All 20 patients, of whom 80% were female, suffered from idiopathic or neurogenic UR for a median 60 months (7-440 months) before SNM. Median patient age was 51 years (34-68 years). Eighteen (90%) of the stimulated patients showed significant success with implantation of IPG within a median of 43 days (15-93). In the follow-up period, postvoid residual (PVR) urine of the permanent stimulated patients was reduced from a median of 350 mL to 135 mL. While this just did not reach statistical significance (p= 0.057), the median number of intermittent catheterizations (ICs) could be reduced relevantly from four to one per day (p= 0.021). The subgroup analysis of idiopathic and neurogenic UR showed relevant improvement of the vital parameters, but the number of patients was obviously too small to yield statistically significant results. Subgroup analysis according to the number of electrodes implanted revealed statistically significant reduction of IC only after unilateral SNM. PVR of <=400 mL was a statistically significant predictor for success of SNM treatment. In the presented treatment period, only one mild adverse event occurred that could be handled conservatively. CONCLUSIONS: SNM can be a successful and secure second line therapy option for patients with chronic UR. Data suggest a more success promising situation for idiopathic cause of disease, but the number of patients was too small to reach statistical significance. Further prospective, randomized multicenter data concerning indications and number of electrodes are necessary and highly appreciated. PMID- 22672286 TI - Subjective memory impairment, objective cognitive functioning and social activity in French older people: findings from the Three Cities study. AB - AIM: To investigate the association between subjective memory impairment (SMI) and objective cognitive impairment in later life, and to ascertain whether this is modified by level of social activity, education or living alone. METHODS: Data were analyzed from three French community surveys carried out in Bordeaux, Dijon and Montpellier. Representative samples of 9294 residents aged 65 years and over were included in the study. SMI was ascertained and investigated in relation to performance on the Benton Visual Retention Test (BVRT), the Isaac Set Test (IST) and Trail Making Test B (TMT). Adjustments were made for age, sex, education, depressive symptoms (Centre for Epidemiological Depression scale), site where study was carried out and living alone. Stratified analyses investigated modification by high or low social activity, education or living arrangement. RESULTS: SMI was reported by 21.9% of the sample, and was significantly associated with lower scores on BVRT and TMT after adjustment for age, sex, education, depressive symptoms, site and living alone. These associations were not significantly modified by social activity, education or living alone. CONCLUSION: Worse subjective memory was associated independently with worse performance on two tests of cognitive function; however, in these cohorts, no evidence was found for modification of associations by social activity/support or education. PMID- 22672288 TI - Significance of decoy receptor 3 (Dcr3) and external-signal regulated kinase 1/2 (Erk1/2) in gastric cancer. AB - BACKGROUND: Decoy receptor 3 (DcR3), a member of the tumor necrosis factor receptor (TNFR) superfamily, is associated with anti-tumor immunity suppression. It is highly expressed in many tumors, and its expression can be regulated by the MAPK/MEK/ERK signaling pathway. The MAPK/MEK/ERK pathway has been reported to be a regulator in tumor occurrence, development and clonal expansion. External signal regulated kinase (ERK) is a vital member of this pathway. RESULTS: The expression of DcR3 and ERK1/2 in tumor tissues of gastric cancer patients was significantly higher than the non-cancerous group (P < 0.05). There was no statistical difference among tumor tissues from patients with different ages or gender, and even of different differentiation (P > 0.05). However, in patients with stage I gastric cancer, the DcR3 and ERK1/2 levels were significantly lower than patients with more advanced stages. CONCLUSIONS: DcR3 and ERK1/2 play a vital role in the development of gastric cancer, and they may be new markers for indicating the efficiency of gastric cancer treatment in the future. PMID- 22672287 TI - A protocol for a randomized clinical trial of interactive video dance: potential for effects on cognitive function. AB - BACKGROUND: Physical exercise has the potential to affect cognitive function, but most evidence to date focuses on cognitive effects of fitness training. Cognitive exercise also may influence cognitive function, but many cognitive training paradigms have failed to provide carry-over to daily cognitive function. Video games provide a broader, more contextual approach to cognitive training that may induce cognitive gains and have carry over to daily function. Most video games do not involve physical exercise, but some novel forms of interactive video games combine physical activity and cognitive challenge. METHODS/DESIGN: This paper describes a randomized clinical trial in 168 postmenopausal sedentary overweight women that compares an interactive video dance game with brisk walking and delayed entry controls. The primary endpoint is adherence to activity at six months. Additional endpoints include aspects of physical and mental health. We focus this report primarily on the rationale and plans for assessment of multiple cognitive functions. DISCUSSION: This randomized clinical trial may provide new information about the cognitive effects of interactive videodance. It is also the first trial to examine physical and cognitive effects in older women. Interactive video games may offer novel strategies to promote physical activity and health across the life span.The study is IRB approved and the number is: PRO08080012ClinicalTrials.gov Identifier: NCT01443455. PMID- 22672290 TI - A pocket-sized disposable device for testing the integrity of sensation in the outpatient setting. AB - AIMS: To compare the Ipswich Touch Test and the VibraTip with the Neuropathy Disability Score and the vibration perception threshold for detecting the 'at risk' foot. METHODS: We directly compared the Ipswich Touch Test and the VibraTip with both the Neuropathy Disability Score >= 6 and the vibration perception threshold >= 25 V indicating 'at-risk' feet in 83 individuals. RESULTS: The vibration perception threshold and Neuropathy Disability Score tests exhibited almost perfect agreement with each other (P < 0.001). The VibraTip and Ipswich Touch Test results were identical (P < 0.001). The VibraTip and Ipswich Touch Test results also exhibited almost perfect agreement with the vibration perception threshold (P < 0.001) and the Neuropathy Disability Score (P < 0.001). CONCLUSIONS: These two simple and efficient tests are easy to teach, reliable and can be used in any setting, and neither requires an external power source. We conclude that both the VibraTip and the Ipswich Touch Test are reliable and sensitive tests for identifying the 'high-risk' foot. PMID- 22672289 TI - Obstetric outcome in donor oocyte pregnancies: a matched-pair analysis. AB - BACKGROUND: To investigate the obstetrical and perinatal impact of oocyte donation, a cohort of women who conceived after OD was compared with a matched control group of women who became pregnant through in vitro fertilisation with autologous oocytes (AO). METHODS: A matched-pair analysis has been performed at the Centre for Reproductive Medicine of the UZ Brussel, Dutch speaking Free University of Brussel. A total of 410 pregnancies resulted in birth beyond 20 weeks of gestation occurring over a period of 10 years, including 205 oocyte donation pregnancies and 205 ICSI pregnancies with autologous oocytes (AO). Patients in the OD group were matched on a one-to-one basis with the AO group in terms of age, ethnicity, parity and plurality. Matched groups were compared using paired t-tests for continuous variables and McNemar test for categorical variables. A conditional logistic regression analyses was performed adjusting for paternal age, age of the oocyte donor, number of embryos transferred, and singleton/twin pregnancy. RESULTS: Oocyte donation was associated with an increased risk of pregnancy induced hypertension (PIH) (matched OR: 1.502 CI: 1.024-2.204), and first trimester bleeding (matched OR: 1.493 CI: 1.036-2.15). No differences were observed between the two matched groups with regard to gestational age, mean birth weight and length, head circumference and Apgar scores. CONCLUSIONS: Oocyte donation is associated with an increased risk for PIH and first trimester bleeding independent of the recipients' age, parity and plurality, and independent of the age of the donor or the partner. However, oocyte donation has no impact on the overall perinatal outcome. PMID- 22672291 TI - Efficient production of an engineered apoptin from chicken anemia virus in a recombinant E. coli for tumor therapeutic applications. AB - BACKGROUND: Apoptin, a nonstructural protein encoded by the VP3 gene of chicken anemia virus (CAV), has been shown to not only induce apoptosis when introduced into the precursors of chicken thymocytes, but has been found to specifically kill human cancer cells, tumor cell and transformed cells without affecting the proliferation of normal cells. This tumor-specific apoptotic characteristic of the protein potentially may allow the development of a protein drug that has applications in tumor therapy. However, several major problems, which include poor expression and poor protein solubility, have hampered the production of apoptin in bacteria. RESULTS: Significantly increased expression of recombinant full-length apoptin that originated from chicken anemia virus was demonstrated using an E. coli expression system. The CAV VP3 gene was fused with a synthetic sequence containing a trans-acting activator of transcription (TAT) protein transduction domain (PTD). The resulting construct was cloned into various different expression vectors and these were then expressed in various E. coli strains. The expression of the TAT-Apoptin in E. coli was significantly increased when TAT-Apoptin was fused with GST-tag rather than a His-tag. When the various rare amino acid codons of apoptin were optimized, the expression level of the GST TAT-Apoptin(opt) in E. coli BL21(DE3) was significantly further increased. The highest protein expression level obtained was 8.33 g/L per liter of bacterial culture after induction with 0.1 mM IPTG for 4 h at 25 degrees C. Moreover, approximately 90% of the expressed GST-TAT-Apoptin(opt) under these conditions was soluble. After purification by GST affinity chromatography, the purified recombinant TAT-Apoptin(opt) protein was used to evaluate the recombinant protein's apoptotic activity on tumor cells. The results demonstrated that the E. coli-expressed GST-TAT-apoptin(opt) showed apoptotic activity and was able to induce human premyelocytic leukemia HL-60 cells to enter apoptosis. CONCLUSIONS: On expression in E. coli, purified recombinant TAT-Apoptin(opt) that has been fused to a GST tag and had its codons optimized, was found to have great potential. This protein may in the future allow the development of a therapeutic protein that is able to specifically kill tumor cells. PMID- 22672292 TI - Echocardiographic guidance of percutaneous patent foramen ovale closure: head-to head comparison of transesophageal versus rotational intracardiac echocardiography. AB - BACKGROUND: Transesophageal (TEE) and intracardiac (ICE) echocardiography are commonly used to guide percutaneous patent foramen ovale (PFO) closure. The study aim was to perform a head-to-head comparison between TEE and rotational ICE echocardiography in the measurement of the fossa ovalis and device selection. METHODS: In 45 patients with cryptogenic stroke or peripheral embolism and PFO with large right-to-left shunt, fossa ovalis dimensions were assessed preoperatively by TEE and intraoperatively by rotational ICE. The Amplatzer devices, deployed on the basis of ICE, were compared with those that would have been selected by TEE. RESULTS: A good correlation between TEE and rotational ICE was observed for both longitudinal and transverse fossa ovalis dimensions (TEE four-chamber vs. ICE four-chamber: r = 0.75; TEE bicaval vs. ICE four-chamber: r = 0.77; TEE aorta vs. ICE aorta: r = 0.59; P < 0.001 for all). However, no such correlation was found in 13 patients with atrial septal aneurysm (ASA) (TEE four chamber vs. ICE four-chamber: r = 0.33; TEE bicaval vs. ICE four-chamber: r = 0.49; TEE aorta vs. ICE aorta: r = 0.05; P = NS for all). At Bland-Altman analysis, slight systematic differences with wide limits of agreement for each comparison were observed, particularly in patients with ASA, suggesting that the two imaging modalities cannot be used interchangeably. As regards device selection, a moderate agreement was found between TEE- and ICE-guided device size (72%, kappa = 0.53, P < 0.001), except in patients with ASA (36%, kappa = 0.02, P = NS). CONCLUSIONS: Our study suggests a significant disagreement between TEE and rotational ICE in measuring fossa ovalis and selecting the device for PFO closure, particularly in patients with ASA. PMID- 22672293 TI - Myths or legends and RAS. PMID- 22672294 TI - Marathon of eponyms: 26 Zinsser-Engman-Cole syndrome (Dyskeratosis congenita). AB - The use of eponyms has long been contentious, but many remain in common use, as discussed elsewhere (Editorial: Oral Diseases. 2009: 15; 185). The use of eponyms in diseases of the head and neck is found mainly in specialties dealing with medically compromised individuals (paediatric dentistry, special care dentistry, oral and maxillofacial medicine, oral and maxillofacial pathology, oral and maxillofacial radiology and oral and maxillofacial surgery) and particularly by hospital-centred practitioners. This series has selected some of the more recognised relevant eponymous conditions and presents them alphabetically. The information is based largely on data available from MEDLINE and a number of internet websites as noted below: the authors would welcome any corrections. This document summarises data about Zinsser-Engman-Cole syndrome. PMID- 22672296 TI - Antidepressant effects on emotional temperament: toward a biobehavioral research paradigm for major depressive disorder. AB - BACKGROUND: Given the limited efficacy of current pharmacotherapy for major depressive disorder (MDD) and the historical decline in antidepressant development, there is increasing clinical urgency to develop more effective treatments. OBJECTIVES: To synthesize findings from clinical psychology and affective neuroscience related to the construct of emotional temperament; to examine the effects of antidepressants on the temperament dimensions of positive (PA) and negative affectivity (NA); and to propose a biobehavioral research paradigm for the treatment of MDD. METHODS: We begin with an introduction to PA and NA, which emphasizes their construct development, historical context, and relevance to psychopathology. We then review studies of antidepressant effects on PA and NA, and explore two related hypotheses: (1) Cause-correction: The antidepressant response may fundamentally occur through changes in emotional temperament, with subsequent spread to syndrome or symptom changes; (2) preferential effects: Antidepressants with different mechanisms of action may have preferential effects on PA or NA. RESULTS: Preliminary findings appear to support the cause-correction hypothesis; there is insufficient clinical evidence to support the preferential effects hypothesis. CONCLUSIONS: PA and NA are biologically based temperament dimensions, which modulate emotional, motivational, and behavioral responses to positive and negative incentives. They can be altered by antidepressants, and may independently contribute to depression improvement. In addition, the distinct biobehavioral features of PA and NA suggest that combined pharmacological and cognitive-behavioral treatments targeting these dimensions may have specific, and perhaps, synergistic antidepressant effects. PMID- 22672297 TI - Human cytomegalovirus linked to stroke in a Chinese population. AB - AIM: Human cytomegalovirus (HCMV) is implicated in several cardiovascular disorders, including atherosclerosis, coronary heart disease, and cardiac transplant arteriopathy. We aimed to evaluate the relationship between HCMV and stroke. METHODS: Real-time polymerase chain reaction (PCR) and ELISA were performed on plasma samples isolated from 200 patients diagnosed with stroke and 200 controls. All participants belonged to the Stroke Hypertension Investigation in Genetics (SHINING) study. RESULTS: HCMV seropositivity was higher in the stroke group than in controls (55.0% vs. 23.5%; P < 0.0001). The presence of HCMV DNA increased the risk of stroke (unadjusted odds ratio [OR], 3.98; 95% confidence interval [CI], 2.59 to 6.11; P < 0.0001). Risks were also increased for the subtypes ischemic stroke (unadjusted OR, 4.01; 95% CI, 2.57-6.24; P < 0.0001) and hemorrhagic stroke (unadjusted OR, 3.80; 95% CI, 1.64-8.78; P= 0.0018). Increased risk with HCMV remained significant after adjustment for age, sex, body mass index, hypertension, and smoking (ischemic stroke: adjusted OR, 4.07; 95% CI, 2.52-6.32; P < 0.0001; hemorrhagic stroke: adjusted OR, 3.88; 95% CI, 1.61-9.36; P= 0.0026). CONCLUSIONS: We demonstrate a novel link between HCMV infection and stroke. These findings may provide important insights into the pathogenesis of stroke. PMID- 22672298 TI - Female early adult depression results in detrimental impacts on the behavioral performance and brain development in offspring. AB - AIMS: The present study was to understand whether early adult depressive females implicated their offspring. METHODS: Seven-week-old female mice were subject to chronic mild stress (CMS) to establish the animal model of depression. The behavioral performance of their offspring were tested via neonatal reflexes tests, hole-board test, and morris water maze test in different ages. Astrocyte number, hippocampal volume, and neurogenesis were analyzed via immunohistochemical blotting. Glucocorticoid receptor (GR) expression and serum cortisol levels were measured by western blotting and ELISA. RESULTS: Female depressive mice had normal fertility, but their offspring had lowered neonatal survival rate and body weight from neonatal period to early adulthood. The offspring of female depressive mice exhibited the impairments of neonatal reflex attainment and memory, but had higher emotionality as adults. Furthermore, the astrocyte number, hippocampal volume, and neurogenesis were reduced in the offspring. However, the expressions of GR were increased in the hippocampus of offspring. CONCLUSION: This study reveals that female early adult depressive mice have normal reproductive ability, but make long-term detrimental impacts on the behavioral performance and brain development of their offspring. PMID- 22672299 TI - Synergic effects of levamlodipine and bisoprolol on blood pressure reduction and organ protection in spontaneously hypertensive rats. AB - AIMS: Stroke is a major cause of disability and death worldwide. Hypertension is one of the most important risk factors for stroke. The objective of this work was to study the synergic effects of levamlodipine and bisoprolol on blood pressure reduction and organ protection in spontaneously hypertensive rats (SHR). METHODS: Blood pressure was continuously monitored in conscious SHR. For acute study, a single dose of drugs was administrated via an intragastric catheter. For chronic study (4 months), drugs were delivered via rat chow. RESULTS: A single dose of levamlodipine (from 1 mg/kg), bisoprolol (from 0.125 mg/kg), and their combinations significantly decreased blood pressure. The levamlodipine-induced tachycardia and the bisoprolol-induced bradycardia were temporized by the combination of these two drugs. Upon chronic treatment, this combination also decreased blood pressure variability and reduced organ damage. CONCLUSION: Levamlodipine and bisoprolol produce synergic effects on blood pressure reduction and organ protection in SHR. PMID- 22672300 TI - Time course of depression and one-year prognosis of patients with stroke in mainland China. AB - AIMS: To investigate the incidence of depression at different time points within the first year after stroke in mainland China and to identify risk factors related to a poor 1-year prognosis in stroke patients. METHODS: Subjects with acute cerebrovascular diseases were recruited and enrolled from 56 hospitals in mainland China between April 2008 and April 2010. Demographic data, previous disease history, and clinical data were collected. Four follow-up visits were occurred within the first year after stroke. The modified Rankin Scale >= 2 represents an unfavorable prognosis. Depression was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition and was divided into persistent, recurrent and transient types. RESULTS: The 1-year cumulative incidence of depression in stroke patients was 41.8%. Logistic regression analysis showed that the 1-year prognosis level was associated with age, disability before onset, neurological functional deficit level at admission, and a range of depression types. The odds ratio for persistent depression is the highest (OR = 7.615, P < 0.0001, 95% confidence interval 5.011-11.572). CONCLUSIONS: In our study, depression occurred in >40% of patients within the first year after stroke. Persistent depression is the first independent determinant of prognosis during the first year after stroke. PMID- 22672301 TI - A new simple model for prediction of hospital mortality in patients with intracerebral hemorrhage. AB - BACKGROUND: The current prognostic models for mortality and functional outcome after intracerebral hemorrhage (ICH) are not simple enough. To predict the outcome of ICH, a new simple model, ICH index (ICHI), was established and evaluated in this study. METHODS: Medical records of all cases with ICH in our hospital from January 2008 to August 2009 were reviewed. Multiple linear regression analyses were used to assess the contributions of independent variables to hospital mortality after ICH. RESULTS: Age, serum glucose, white blood cell counts (WBC), and Glasgow Coma Scale (GCS) score were found to be greatly associated with mortality. A formula of ICH index [ICHI = age (years)/10 + glucose (mmol/L) + WBC (10(9) /L) - GCS score] was established. Furthermore, the receiver operating characteristic (ROC) analyses were performed to estimate the predictive value of the ICHI. The model showed an area under the ROC curve (AURC) of 0.923 (95% CI: 0.883-0.963, P < 0.001). The best cut-off value of ICHI for mortality was 18, which gave sensitivity, specificity, and Youden's index of 0.65, 0.95, and 0.60, respectively. The hospital mortality was extremely increased when 18 < ICHI < 28 (mortality 72.0%) and when ICHI >= 28 (mortality 100%), in contrast with overall mortality (21.6%). CONCLUSION: The ICHI can be a simple predictive model and complementary to other prognostic models. PMID- 22672302 TI - NPY intraperitoneal injections produce antidepressant-like effects and downregulate BDNF in the rat hypothalamus. AB - AIMS: Several studies have documented an involvement of Neuropeptide Y (NPY) in stress-related disorders. Stress-related disorders are also characterized by changes in brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), neurotrophins implicated in the survival and function of neurons. Thus the aim of this study was to investigate whether an NPY intraperitoneal treatment has antidepressant-like effects in rats subjected to a classical stress paradigm, the Forced Swim Test (FST), in association with changes in local brain neurotrophin production. METHODS: Rats were intraperitoneally injected with either NPY (60 MUg/kg) or a vehicle for three consecutive days between two FST sessions and then tested for time spent (or delay onset) in immobile posture. Moreover, we measured by enzyme-linked immunosorbent assay (ELISA) neurotrophin levels in the hypothalamus and corticosterone levels in plasma. RESULTS: The data showed that NPY induced a significant delay in the onset and a significant reduction in the duration of the immobility posture in FST. We also found that NPY decreased BDNF levels in the hypothalamus and corticosterone levels in plasma. DISCUSSION: Immobility posture in FST can be reduced by antidepressant drugs. Thus, our data show an antidepressant-like effect of NPY associated with changes in BDNF levels in the hypothalamus and reduced activity of hypothalamic-pituitary-adrenal (HPA) axis. CONCLUSION: These findings, while confirming the involvement of the NPY system in stress-related disorders, suggest that a less invasive route of administration, such as an intraperitoneal injection, may be instrumental in coping with stressful events in animal models and perhaps in humans. PMID- 22672303 TI - Drug binding assays do not reveal specific binding of lacosamide to collapsin response mediator protein 2 (CRMP-2). AB - AIMS: Lacosamide (LCM; SPM 927, Vimpat(r)) is an antiepileptic drug (AED) used as adjunctive treatment for adults with partial-onset seizures. LCM has a different mode of action from traditional sodium channel blocking AEDs in that it selectively enhances slow inactivation of sodium channels without affecting fast inactivation. Initial investigations suggested that LCM might have an additional mode of action by binding to the collapsin response mediator protein 2 (CRMP-2), which is further investigated here. METHODS: LCM binding to native and cloned human CRMP-2 was determined using radioligand binding experiments and surface plasmon resonance measurements. RESULTS: No specific binding of [(3) H]LCM (free concentration 100-1450 nM) to isolated or membrane bound human CRMP-2 expressed in mammalian cell systems and bacteria was observed. Surface plasmon resonance analysis also showed that LCM, over a concentration range of 0.39-100 MUM, does not specifically bind to human CRMP-2. CONCLUSION: The diverse drug binding methods employed here are well suited to detect specific binding of LCM to CRMP-2 in the micromolar range, yet the results obtained were all negative. Results of this study suggest that LCM does not specifically bind to CRMP-2. PMID- 22672304 TI - Meta-analysis of association between particulate matter and stroke attack. AB - AIMS: We conducted systematic review as well as meta-analyses on the association between particulate matter and daily stroke attack from a number of epidemiologic studies. METHODS: Twelve quantitative studies about the associations between particulate matter and stroke attack met the inclusive criteria. We evaluated the odds ratio (OR) of stroke attack associated with per 10 MUg/m(3) increase of the concentration of PM(10) (particulate matter with aerodynamic diameter <= 10 MUm) or PM(2.5) (particulate matter with aerodynamic diameter <= 2.5 MUm) as effect scale, and a sensitivity analysis for the results was conducted. RESULTS: In the time-series design, PM(10) exposure wasn't related to an increased risk of daily stroke attack [OR per 10 MUg/m(3) = 1.002, 95% confidence interval (CI): 0.999~1.005], PM(2.5) exposure were related to an increased risk of daily stroke attack (OR per 10 MUg/m(3) = 1.006, 95%CI: 1.002~1.010]; but in the case crossover studies, PM(10) exposure was related to increase in risk of daily stroke attack (OR per 10 MUg/m(3) = 1.028, 95%CI: 1.001~1.057). PM(2.5) exposure was not significant association with daily stroke attack (OR per 10 MUg/m(3) = 1.016, 95%CI: 0.937~1.097). Sensitivity analysis showed that the results for PM(10) , PM(2.5) and daily stroke attack were robust in the time-series design. CONCLUSIONS: We found some evidence for an effect of air pollutants on stroke attack risk. PMID- 22672305 TI - Mephentermine dependence: an emerging challenge. PMID- 22672306 TI - Protection of different components of Danshen in cerebral infarction in mice. PMID- 22672307 TI - A substance P antagonist improves outcome in female Sprague Dawley rats following diffuse traumatic brain injury. PMID- 22672308 TI - Efficacy of a penile variable tension loop for improving climacturia after radical prostatectomy. AB - WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Climacturia is present in ~20-40% of men after radical prostatectomy, and adversely affects sexual satisfaction. Although several strategies have been proposed for the treatment of climacturia, none have been systematically studied to date. This observational study shows that use of a penile variable tension loop can significantly reduce the degree and frequency of orgasm-associated incontinence, and the associated distress experienced by patients and partners. Climacturia resolves completely in half the patients, and occurs occasionally or rarely in the remainder. OBJECTIVE: To define the impact of the use of a penile variable tension loop on climacturia and on the distress level experienced by patients and their partners as a result of climacturia. PATIENTS AND METHODS: All patients presenting for sexual function assessment after radical prostatectomy (RP) were questioned regarding climacturia. The study population consisted of men who had undergone RP < 6 months before initial evaluation, had reported having climacturia on >=25% attempts where orgasm was achieved, had agreed to use the variable tension loop consistently, and continued to have climacturia when not using the loop at follow up. Patients were interviewed regarding the frequency and degree of climacturia, and their own and their partner's distress levels secondary to climacturia, both with and without the use of the variable tension loop. RESULTS: The study population comprised 124 men. At baseline, the degree of climacturia was small, moderate, and large in 16%, 72%, 12% of patients, respectively, and 28%, 26% and 0%, respectively, at follow-up (all P < 0.01). Climacturia occurred rarely, occasionally, most of the time, or always in 15%, 48%, 16% and 21% of cases, respectively, at baseline, and 48% of patients experienced no climacturia with use of the variable tension loop. Distress was experienced by 14% and 61% of patients and partners at baseline, and 2% and 11% of patients and partners at follow up (P < 0.01). Severity of distress was significantly lower at follow-up for both partners and patients (P < 0.01). CONCLUSIONS: Climacturia is a common complication of radical prostatectomy. Application of the variable tension loop can result in a significant decrease in the frequency and volume of climacturia. Use of the variable tension loop is a simple and non-invasive strategy for relieving the distress associated with climacturia in patients who have undergone RP and their partners. PMID- 22672309 TI - Equisetum arvense hydromethanolic extracts in bone tissue regeneration: in vitro osteoblastic modulation and antibacterial activity. AB - OBJECTIVES: Equisetum arvense preparations have long been used to promote bone healing. The aim of this work was to evaluate osteogenic and antibacterial effects of E. arvense hydromethanolic extracts. MATERIALS AND METHODS: Dried aerial components of E. arvense were extracted using a mixture of methanol:water (1:1), for 26 days, yielding three extracts that were tested (10-1000 MUg/ml) in human osteoblastic cells: E1, E2 and EM (a mixture of E1 and E2, 1:1). Cell cultures, performed on cell culture plates or over hydroxyapatite (HA) substrates, were assessed for osteoblastic markers. In addition, effects of the extracts on Staphylococcus aureus were addressed. RESULTS: Solution E1 caused increased viability/proliferation and ALP activity at 50-500 MUg/ml, and deleterious effects at levels >=1000 MUg/ml. E2 inhibited cell proliferation at levels >=500 MUg/ml. EM presented a profile between those observed with E1 and E2. In addition, E1, E2 and EM, 10-1000 MUg/ml, inhibited expansion of S. aureus. Furthermore, E1, tested in HA substrates colonized with osteoblastic cells, causing increase in cell population growth (10-100 MUg/ml). E1 also exhibited antibacterial activity against S. aureus cultured over HA. CONCLUSIONS: Results showed that E. arvense extracts elicited inductive effects on human osteoblasts while inhibiting activity of S. aureus, suggesting a potentially interesting profile regarding bone regeneration strategies. PMID- 22672312 TI - White papules on the face, neck and upper chest. Birt-Hogg-Dube syndrome. PMID- 22672311 TI - Increasing the presence of biofilm and healing delay in a porcine model of MRSA infected wounds. AB - Data supporting the concept that microbial biofilms are a major cause of non healing ulcers remain limited. A porcine model was established where delayed healing resulted from methicillin-resistant Staphylococcus aureus (MRSA) infection in full-thickness wounds. At the end of one study a wound remaining open was sampled and a MRSA strain was isolated. This pig-passaged strain was used as the inoculating strain in several subsequent studies. The resulting MRSA wound infections exhibited a greater, more stable tissue bioburden than seen in studies using the parent strain. Furthermore, wounds infected with the passaged strain experienced a greater delay in healing. To understand whether these changes corresponded to an increased biofilm character of the wound infection, wound biopsy samples from studies using either the parent or passaged MRSA strains were examined microscopically. Evidence of biofilm was observed for both strains, as most samples at a minimum had multiple isolated, dense microcolonies of bacteria. However, the passaged MRSA resulted in bacterial colonies of greater frequency and size that occurred more often in concatenated fashion to generate extended sections of biofilm. These results provide a model case in which increasing biofilm character of a wound infection corresponded with a greater delay in wound healing. PMID- 22672310 TI - Modulation of Caenorhabditis elegans infection sensitivity by the LIN-7 cell junction protein. AB - In Caenorhabditis elegans, the LIN-2/7/10 protein complex regulates the activity of signalling proteins. We found that inhibiting lin-7 function, and also lin-2 and lin-10, resulted in enhanced C. elegans survival after infection by Burkholderia spp., implicating a novel role for these genes in modulating infection outcomes. Genetic experiments suggested that this infection phenotype is likely caused by modulation of the DAF-2 insulin/IGF-1 signalling pathway. Supporting these observations, yeast two-hybrid assays confirmed that the LIN-2 PDZ domain can physically bind to the DAF-2 C-terminus. Loss of lin-7 activity also altered DAF-16 nuclear localization kinetics, indicating an additional contribution by hsf-1. Unexpectedly, silencing lin-7 in the hypodermis, but not the intestine, was protective against infection, implicating the hypodermis as a key tissue in this phenomenon. Finally, consistent with lin-7 acting as a general host infection factor, lin-7 mutants also exhibited enhanced survival upon infection by two other Gram-negative pathogens, Pseudomonas and Salmonella spp. PMID- 22672314 TI - Phagocytosis here and now. PMID- 22672313 TI - The effectiveness of oral appliances in elderly patients with obstructive sleep apnoea treated with lorazepam--a pilot study. AB - Obstructive sleep apnoea (OSA) is one of the most common sleep disorders in elderly and represents a special problem for elderly patients. Elderly patients use a large number of drugs that might have an influence on the upper airway structure, anxiolytics or benzodiazepines being the most common. The aim of this study was to examine the effectiveness of mild or moderate OSA treatment with mandibular advance oral appliance in older lorazepam users compared with the age matched lorazepam-free patients. A total of 40 functionally independent patients with the age of 65-74 were enrolled in the study. All included patients were found to suffer from at least two of the existing OSA symptoms (snoring, sleep fragmentation, daytime sleepiness) and were diagnosed with mild or moderate OSA after nocturnal polysomnography. Patients were divided into two groups. The experimental group consisted of 20 patients who used lorazepam in their daily therapy, and a control group consisted of 20 patients who did not take lorazepam. A mandibular advance appliance was made individually for each patient. Patients involved in the study were not overweight and were suggested to practise sleeping on the side and reduce alcohol consumption during the study. The study has shown that mandibular advance oral appliances were responsible for complete control of the OSA in over 37% of cases (15 patients). Patients have also reported substantial improvement in the symptoms; 80% of them reported that they had snored less, slept better (94%) and have not experienced daytime sleepiness (100%). PMID- 22672315 TI - The development, distribution and density of the plasma membrane calcium ATPase 2 calcium pump in rat cochlear hair cells. AB - Calcium is tightly regulated in cochlear outer hair cells (OHCs). It enters mainly via mechanotransducer (MT) channels and is extruded by the plasma membrane calcium ATPase (PMCA)2 isoform of the PMCA, mutations in which cause hearing loss. To assess how pump expression matches the demands of Ca(2+) homeostasis, the distribution of PMCA2 at different cochlear locations during development was quantified using immunofluorescence and post-embedding immunogold labeling. The PMCA2 isoform was confined to stereociliary bundles, first appearing at the base of the cochlea around post-natal day (P)0 followed by the middle and then the apex by P3, and was unchanged after P8. The developmental appearance matched the maturation of the MT channels in rat OHCs. High-resolution immunogold labeling in adult rats showed that PMCA2 was distributed along the membranes of all three rows of OHC stereocilia at similar densities and at about a quarter of the density in inner hair cell stereocilia. The difference between OHCs and inner hair cells was similar to the ratio of their MT channel resting open probabilities. Gold particle counts revealed no difference in PMCA2 density between low- and high-frequency OHC bundles despite larger MT currents in high frequency OHCs. The PMCA2 density in OHC stereocilia was determined in low- and high-frequency regions from calibration of immunogold particle counts as 2200/MUm(2) from which an extrusion rate of ~200 ions/s per pump was inferred. The limited ability of PMCA2 to extrude the Ca(2+) load through MT channels may constitute a major cause of OHC vulnerability and high-frequency hearing loss. PMID- 22672316 TI - The partitioning of water uptake between growth forms in a Neotropical savanna: do herbs exploit a third water source niche? AB - In addition to trees and grasses, the savannas of central Brazil are characterised by a diverse herbaceous dicot flora. Here we tested whether the coexistence of a highly diversified assemblage of species resulted in stratification or strong overlap in the use of soil water resources. We measured oxygen and hydrogen isotope ratios of stem water from herbs, grasses and trees growing side by side, as well as the isotopic composition of water in soil profile, groundwater and rainfall, and predawn (Psi(pd)) and midday (Psi(md)) leaf water potentials. We used a stable isotope mixing model to estimate vertical partitioning of soil water by the three growth forms. Grasses relied on shallow soil water (5-50 cm) and were strongly anisohydric. Psi(pd) and Psi(md) decreased significantly from the wet to the dry season. Trees extracted water from deeper regions of the soil profile (60-120 cm) and were isohydric. Psi(pd) and Psi(md) did not change from the wet to the dry season. Herbs overlapped with grasses in patterns of water extraction in the dry season (between 10 and 40 cm), but they took up water at soil depths intermediate (70-100 cm) to those of trees and grasses during the wet season. They showed seasonal changes in Psi(pd) but not in Psi(md). We conclude that vertical partitioning of soil water may have contributed to coexistence of these three growth forms and resulted in a more complex pattern of soil water extraction than the two-compartment model of soil water uptake currently used to explain the structure and function of tropical savanna ecosystems. PMID- 22672317 TI - The concept of quality of life and its role in enhancing human rights in the field of intellectual disability. AB - BACKGROUND: The changed societal views of persons with disabilities are reflected in the 2006 United Nations Convention on the Rights of Persons with Disabilities. However, what is not specified in the Convention is how to operationalise and measure the Articles composing the Convention, and how to use that information to further enhance the human rights of persons with disabilities. METHOD: The authors analyse the relationships between eight core quality of life domains and the 34 Articles contained in the Convention. RESULTS: There is a close relationship between the core quality of life domains and the 34 Articles contained in the Convention. Furthermore, the current status of these Articles can be evaluated through the assessment of indicators associated with the eight core quality of life domains. CONCLUSIONS: Based on the assessment of these quality of life-related outcomes, three strategies can be used to enhance the human rights of persons with intellectual disability. These three are to employ person-centred planning, publish provider profiles and implement a system of support. PMID- 22672318 TI - Impact of stage 3B chronic kidney disease on thrombosis and bleeding outcomes after orthopedic surgery in patients treated with desirudin or enoxaparin: insights from a randomized trial. AB - BACKGROUND: Venous thromboembolism (VTE) remains a significant complication of major orthopedic surgery, and chronic kidney disease (CKD) is common among elderly patients undergoing total hip replacement (THR). OBJECTIVES: The purpose of this study was to evaluate thrombosis and bleeding outcomes in patients with stage 3B CKD treated with either desirudin or enoxaparin after elective THR. PATIENTS/METHODS: This was a post hoc subgroup analysis of a randomized, multicenter, double-blind study of desirudin vs. enoxaparin in patients undergoing elective THR. RESULTS: Patients received either subcutaneous desirudin 15 mg twice daily or subcutaneous enoxaparin 40 mg once daily. Of the 2078 randomized patients who received study medication, 577 had stage 3B CKD or worse (27.8%), and the proportion of these patients who experienced a major VTE in the enoxaparin treatment group was found to be much higher than in the desirudin treatment group (11.1% vs. 3.4%, model-adjusted odds ratio 3.52, 95% confidence interval 1.48-8.40, P=0.004). There was no statistically significant difference between treatment groups in terms of rates of major bleeding, regardless of stage of renal function. CONCLUSIONS: CKD has been reported previously to increase the risk of bleeding with anticoagulants, and these findings suggest that CKD may also increase the risk of major VTE for patients treated with enoxaparin, but not for patients treated with desirudin. Clinicians should consider the impact of CKD on the risk of VTE when choosing a prophylaxis agent. PMID- 22672321 TI - Your ideal Sexual Medicine day. PMID- 22672320 TI - Simulation to locate burr hole sites in a patient for deep brain stimulation surgery and clipping of intracranial aneurysm. AB - BACKGROUND AND OBJECTIVE: Deep brain stimulation (DBS) candidates with neurologic diseases such as unruptured aneurysm present additional challenges to neurosurgeons when craniotomy must precede DBS surgery. Such craniotomy may potentially overlap with intended burr hole sites for the later insertion of DBS electrodes, and the skin incision for craniotomy may lie very close to or intersect with that for the burr holes. We report here a case of forehead craniotomy prior to DBS surgery in which we employed a neuronavigation system to simulate locations for the craniotomy and burr holes. METHOD: A 62-year-old male patient with Parkinson's disease was a candidate for DBS. He also had an aneurysm and was planned first to undergo frontal craniotomy for clipping before the DBS surgery. The locations of the craniotomy, burr holes, and skin incisions were therefore simulated using a neuronavigation system during craniotomy. RESULTS: Two weeks after the craniotomy, the patient underwent DBS surgery. Planning software confirmed the absence of cortical veins beneath the entry points of tentative burr holes and aided trajectory planning. The DBS surgery was performed without the interference of the burr holes and head pins and the craniotomy. CONCLUSION: Simulation of the locations of craniotomy and burr holes using a neuronavigation system proved valuable in the present case of frontal craniotomy before DBS surgery. PMID- 22672319 TI - High dose erythropoietin increases brain tissue oxygen tension in severe vasospasm after subarachnoid hemorrhage. AB - BACKGROUND: Vasospasm-related delayed cerebral ischemia (DCI) significantly impacts on outcome after aneurysmal subarachnoid hemorrhage (SAH). Erythropoietin (EPO) may reduce the severity of cerebral vasospasm and improve outcome, however, underlying mechanisms are incompletely understood. In this study, the authors aimed to investigate the effect of EPO on cerebral metabolism and brain tissue oxygen tension (PbtO2). METHODS: Seven consecutive poor grade SAH patients with multimodal neuromonitoring (MM) received systemic EPO therapy (30.000 IU per day for 3 consecutive days) for severe cerebral vasospasm. Cerebral perfusion pressure (CPP), mean arterial blood pressure (MAP), intracranial pressure (ICP), PbtO2 and brain metabolic changes were analyzed during the next 24 hours after each dose given. Statistical analysis was performed with a mixed effects model. RESULTS: A total of 22 interventions were analyzed. Median age was 47 years (32 68) and 86 % were female. Three patients (38 %) developed DCI. MAP decreased 2 hours after intervention (P < 0.04) without significantly affecting CPP and ICP. PbtO2 significantly increased over time (P < 0.05) to a maximum of 7 +/- 4 mmHg increase 16 hours after infusion. Brain metabolic parameters did not change over time. CONCLUSIONS: EPO increases PbtO2 in poor grade SAH patients with severe cerebral vasospasm. The effect on outcome needs further investigation. PMID- 22672323 TI - Report on ISSWSH fellowship. PMID- 22672324 TI - Characterization of Salmonella enterica serovar Enteritidis isolates recovered from blood and stool specimens in Thailand. AB - BACKGROUND: Bacteremia due to Salmonella spp. is a life-threatening condition and is commonly associated with immune compromise. A 2009 observational study estimated risk factors for the ten most common non-typhoidal Salmonella (NTS) serovars isolated from Thai patients between 2002-2007. In this study, 60.8% of Salmonella enterica serovar Enteritidis isolates (n = 1517) were recovered from blood specimens and infection with Salmonella serovar Enteritidis was a statistically significant risk factor for bacteremia when compared to other NTS serovars. Based on this information, we characterized a subset of isolates collected in 2008 to determine if specific clones were recovered from blood or stool specimens at a higher rate. Twenty blood isolates and 20 stool isolates were selected for antimicrobial resistance testing (MIC), phage typing, PFGE, and MLVA. RESULT: Eight antibiogrammes, seven MLVA types, 14 XbaI/BlnI PFGE pattern combinations, and 11 phage types were observed indicating considerable diversity among the 40 isolates characterized. Composite analysis based on PFGE and MLVA data revealed 22 genotypes. Seven of the genotypes containing two or more isolates were from both stool and blood specimens originating from various months and zones. Additionally, those genotypes were all further discriminated by phage type and/or antibiogramme. Ninety percent of the isolates were ciprofloxacin resistant. CONCLUSIONS: The increased percentage of bloodstream infections as described in the 2009 observational study could not be attributed to a single clone. Future efforts should focus on assessing the immune status of bacteriaemic patients and identifying prevention and control measures, including attribution studies characterizing non-clinical (animal, food, and environmental) isolates. PMID- 22672326 TI - Association of the 4 g/5 g polymorphism of plasminogen activator inhibitor-1 gene with sudden sensorineural hearing loss. A case control study. AB - BACKGROUND: The 5 G/5 G genotype of PAI-1 polymorphism is linked to decreased plasminogen activator inhibitor-1 (PAI-1) levels and it has been suggested that lower PAI-1 levels may provide protective effects on inflammation, local microcirculatory disturbance, and fibrotic changes, which are likely associated with development of sudden sensorineural hearing loss (SSNHL). METHODS: The association of the 4 G/5 G PAI-1 polymorphism with the development and clinical outcome of SSNHL is evaluated via a case control study. 103 patients with SSNHL and 113 age and sex-matched controls were enrolled at University of Ferrara, Italy and hearing loss outcome was measured at least 3 months after the onset of hearing loss. DNA was isolated from peripheral blood using the QIAamp kit and the 4 G/5 G polymorphism in the -675 promoter region was genotyped with an allele specific PCR. Genotype distribution was tested in patients and compared to controls by chi-square and odd-ratio analysis. The codominant and recessive models were used for the multiple logistic regression analyses of the PAI-1 gene allele. RESULTS: In this population, 5 G/5 G genotype had a two-time lower frequency in SSNHL patients compared to healthy controls (15.5% vs 30.1%) and was associated with decreased odds compared to 4 G/5 G genotype (OR 0.37, 95% CI 0.19 0.75, p = 0.005). In addition, the patients with 5 G/5 G genotype showed a trend of more than 2 times higher ratio of hearing recovery (> 20 dB) after systemic corticosteroid treatment compared to 4 G/5 G genotype (OR 2.3, 95% CI 0.32 - 16.83, p = 0.39), suggesting a better clinical outcome. CONCLUSIONS: The 5 G/5 G genotype of PAI-1 may be associated with a reduced risk of SSNHL in the Italian population. PMID- 22672325 TI - Allergens in urban schools and homes of children with asthma. AB - BACKGROUND: Most studies of indoor allergens have focused on the home environment. However, schools may be an important site of allergen exposure for children with asthma. We compared school allergen exposure to home exposure in a cohort of children with asthma. Correlations between settled dust and airborne allergen levels in classrooms were examined. METHODS: Settled dust and airborne samples from 12 inner-city schools were analyzed for indoor allergens using multiplex array technology (MARIA). School samples were linked to students with asthma enrolled in the School Inner-City Asthma Study (SICAS). Settled dust samples from students' bedrooms were analyzed similarly. RESULTS: From schools, 229 settled dust and 197 airborne samples were obtained. From homes, 118 settled dust samples were obtained. Linear mixed regression models of log-transformed variables showed significantly higher settled dust levels of mouse, cat and dog allergens in schools than homes (545% higher for Mus m 1, estimated absolute difference 0.55 MUg/g, p < 0.0001; 198% higher for Fel d 1, estimated absolute difference 0.13 MUg/g, p = 0.0033; and 144% higher for Can f 1, estimated absolute difference 0.05 MUg/g, p = 0.0008). Airborne and settled dust Mus m 1 levels in classrooms were moderately correlated (r = 0.48; p < 0.0001). There were undetectable to very low levels of cockroach and dust mite allergens in both homes and schools. CONCLUSION: Mouse allergen levels in schools were substantial. In general, cat and dog allergen levels were low, but detectable, and were higher in schools. Aerosolization of mouse allergen in classrooms may be a significant exposure for students. Further studies are needed to evaluate the effect of indoor allergen exposure in schools on asthma morbidity in students with asthma. PMID- 22672327 TI - Application of an immune-magnetic cell sorting method for CD138-positive plasma cells in FISH analysis of multiple myeloma. AB - INTRODUCTION: Interphase fluorescence in situ hybridization (FISH) analysis of multiple myeloma (MM) may indiscriminately count signals of nonplasma cells, thus decreasing specificity and sensitivity. We aimed to evaluate the usefulness of an immune-magnetic sorting method for plasma cells in FISH analysis of MM and define optimal sample preparation conditions. METHODS: Plasma cells were purified using EasySep((r)) CD138 Positive Selection Cocktail and Magnetic Nanoparticles (Invitrogen). We compared FISH results with and without plasma cell purification for three sample preparation methods: direct harvest, 24-h culture, and 96-h culture with interleukin-4 in five newly diagnosed MM patients. Archived fixed bone marrow cells of 17 MM patients were also studied. RESULTS: The percentage of abnormal cells identified was significantly higher with plasma cell purification than without purification (median, 88.0%; range, 84.0-100.0%vs. 15.0%, 12.5 29.5%, respectively). The three sample preparation methods showed comparable results. Immune-magnetic sorting also significantly increased the percentage of abnormal cells identified in FISH analysis of archived fixed bone marrow cells (P < 0.001). CONCLUSIONS: Immune-magnetic CD138-positive cell sorting significantly increased the percentage of abnormal cells identified in FISH analysis of MM samples for all sample preparation methods. This method could also be applied for retrospective FISH analysis of archived fixed bone marrow cells. PMID- 22672328 TI - The impact of mitral stenosis on left atrial function assessed by two-dimensional speckle tracking echocardiography. AB - AIMS: The aim of this study is to investigate the effect of mitral stenosis (MS) on left atrial (LA) function using two-dimensional speckle tracking echocardiography (2DSTE). METHODS AND RESULTS: The study subjects consisted of 52 patients with asymptomatic MS and 52 control subjects. LA function was assessed using prototype speckle tracking software and manual tracking method. Maximal LA volume (LAVmax) and minimal LA volume (LAVmin) and LA volume before atrial contraction (LAVpre-a) were measured. Using these volumes, LA reservoir, conduit and booster pump fuction parameters were calculated. Indexed LAVmax, LAVmin, and LAVpre-a measurements via speckle tracking were highly correlated with manual tracing methods in both groups. Expansion index (67.8 +/- 36.4 vs. 148.3 +/- 44.2), diastolic emptying index (37.7 +/- 12.9 vs. 58.0 +/- 8.5), passive emptying (37.3 +/- 14.1 vs. 70.4 +/- 10.4) and passive emptying index (13.3 +/- 6.3 vs. 41.3 +/- 10.6) were decreased significantly in MS patients (P < 0.001). In contrast active emptying index (62.6 +/- 4.1 vs. 29.5 +/- 10.1) increased in MS group (P < 0.001) while active emptying (28.1 +/- 13.0 vs. 28.3 +/- 6.9) remained same among both groups. CONCLUSIONS: This is the first study relating LA volumes and function assessed by 2DSTE to MS. 2D speckle tracking analysis of LA volume is relatively easy and provides more detailed information regarding the changes in LA volumes during the cardiac cycle. PMID- 22672329 TI - Systematic review of care intervention studies for the management of incontinence and promotion of continence in older people in care homes with urinary incontinence as the primary focus (1966-2010). AB - The aim of this paper was to compare published studies of care interventions for the management and promotion of continence, with urinary incontinence as the primary focus, in older care home residents. Incontinence is a prevalent and serious problem amongst older people in care homes, with an increasing international focus. MEDLINE and CINAHL searches via OVID (January 1966 to May 2010) were carried out, with studies limited to English language publications only. Included in this search were studies investigating urinary and fecal incontinence in people aged 65 years or older in care homes. Studies on surgical or pharmacological interventions or fecal incontinence alone were excluded. A total of 33 interventional studies were identified. Toileting programs and incontinence pads are the mainstays of treatment, with some studies implying significant economic and labor costs. Drug therapy as an adjunct to toileting programs has so far shown only moderate benefits. Combined physical therapy/behavioral therapies have shown effective short-term improvements. Adaptations to physical environment and staff training techniques might also be paramount. Exercise and Functional Incidental Training programs, although expensive, might provide additional benefit by reducing wetness rates and improving appropriate toileting rates. Combined complex behavioral interventions are now a common feature and their effectiveness for the management of urinary incontinence should be determined in future studies. Studies including long-term effectiveness on maintaining continence with full economic evaluation are also warranted in this population. PMID- 22672330 TI - Dorothy Hodgkin Lecture 2012: non-alcoholic fatty liver disease, insulin resistance and ectopic fat: a new problem in diabetes management. AB - Non-alcoholic fatty liver disease is now recognized as the hepatic component of the metabolic syndrome. Non-alcoholic fatty liver disease is a spectrum of fat associated liver conditions that can result in end-stage liver disease and the need for liver transplantation. Simple steatosis, or fatty liver, occurs early in non-alcoholic fatty liver disease and may progress to non-alcoholic steatohepatitis, fibrosis and cirrhosis with increased risk of hepatocellular carcinoma. Prevalence estimates for non-alcoholic fatty liver disease range from 17 to 33% in the general populations and it has been estimated that non-alcoholic fatty liver disease exists in up to 70% of people with Type 2 diabetes. Non alcoholic fatty liver disease increases risk of Type 2 diabetes and cardiovascular disease. In people with Type 2 diabetes, non-alcoholic fatty liver disease is the most frequent cause (~80%) of fatty liver diagnosed by ultrasound. As non-alcoholic fatty liver disease is strongly associated with insulin resistance, the presence of non-alcoholic fatty liver disease with diabetes often contributes to poor glycaemic control. Consequently, strategies that decrease liver fat and improve whole-body insulin sensitivity may both contribute to prevention of Type 2 diabetes and to better glycaemic control in people who already have developed diabetes. This review summarizes the Dorothy Hodgkin lecture given by the author at the 2012 Diabetes UK annual scientific conference, proposing that fatty acid fluxes through the liver are crucial for the pathogenesis of non-alcoholic fatty liver disease and for increasing insulin resistance. PMID- 22672331 TI - Developing a national health research system: participatory approaches to legislative, institutional and networking dimensions in Zambia. AB - For many sub-Saharan African countries, a National Health Research System (NHRS) exists more in theory than in reality, with the health system itself receiving the majority of investments. However, this lack of attention to NHRS development can, in fact, frustrate health systems in achieving their desired goals. In this case study, we discuss the ongoing development of Zambia's NHRS. We reflect on our experience in the ongoing consultative development of Zambia's NHRS and offer this reflection and process documentation to those engaged in similar initiatives in other settings. We argue that three streams of concurrent activity are critical in developing an NHRS in a resource-constrained setting: developing a legislative framework to determine and define the system's boundaries and the roles all actors will play within it; creating or strengthening an institution capable of providing coordination, management and guidance to the system; and focusing on networking among institutions and individuals to harmonize, unify and strengthen the overall capacities of the research community. PMID- 22672332 TI - The role of group education on quality of life in patients with a stoma. AB - Stoma education has been traditionally given in a one-to-one setting. Since 2007, daily group education programmes were organised for stoma patients and their relatives by our stoma therapy unit. The programmes included lectures on stoma and stoma care, and social activities in which patients shared their experiences with each other. Patients were also encouraged to expand interaction with each other and organise future social events. A total of 72 patients [44 (61.1%) male with a mean (+/- SD) age of 56.8 +/- 13.6 years] with an ileostomy (n= 51, 70.8%), a colostomy (n= 18, 25.0%) or a urostomy (n= 3, 4.2%) were included in the study. Patients were asked to answer a survey (SF-36) face-to-face before the initiation of the programme, which was repeated 3 months later via telephone call. The comparison of pre-education and post-education SF-36 scores revealed a statistically significant improvement in all 8-scale profiles, but not in vitality scale, and both psychometrically-based and mental health summary measures. Analyses disclosed that married patients and those who were living at rural districts seem to have the most improvement in life quality particularly in bodily pain, general health and role-emotional scales and mental health summary measure. In our opinion, group educations may be beneficial for stoma patients, and stoma therapy units may consider organising similar activities. PMID- 22672333 TI - Immunohistochemical localization of CD1a and S100 in gingival tissues of healthy and chronic periodontitis subjects. AB - OBJECTIVE: The aim of this study was to evaluate the presence and distribution of CD1a and S100 protein markers in states of gingival health and chronic periodontitis in human subjects. MATERIALS AND METHODS: Gingival tissue samples were derived from 10 healthy and 10 chronic periodontitis-affected human subjects. The presence and distribution of CD1a and S100 protein was assessed using immunohistochemistry, and the cell types involved in their expression was determined. RESULTS: The presence and distribution of CD1a was confined only to the gingival epithelium, whereas S100 was seen in the epithelium and connective tissue. However, increased expression of both CD1a and S100 protein was seen in periodontitis-affected gingival tissues compared with healthy gingiva. Immunohistochemistry demonstrated that CD1a- and S100-positive cells in the epithelium are Langerhans cells (LCs) and S100 positive cells in the connective tissue are dendritic cells (DCs). CONCLUSION: Our findings suggest the transition of CD1a-positive LCs to S100-positive DCs from epithelium to connective tissue in response to an antigenic challenge. Demonstration of increased number of S100 positive DCs in the gingival connective tissue in chronic periodontitis possibly suggests their involvement in bone resorption in addition to their antigen presentation property. PMID- 22672334 TI - Treatment of diabetic foot ulcers using cultured allogeneic keratinocytes--a pilot study. AB - Diabetic foot ulcers often pose a difficult treatment problem. Repeated applications of cell-based products have been reported to result in acceleration of diabetic wound healing. The purpose of this clinical trial study was to report preliminary findings of the efficacy and safety of the cultured allogeneic keratinocyte sheets in the treatment of diabetic foot ulcers. Fifty-nine patients with diabetic foot ulcers were randomized to either the keratinocyte treatment group (n = 27) or the control group treated with vaseline gauze (n = 32). Except for the application of keratinocytes, treatment of study ulcers was identical for patients in both groups. Either keratinocyte sheet or vaseline gauze was applied at the beginning of the study and weekly thereafter for a maximum of 11 weeks. The maximum follow-up period for each patient was 12 weeks. Complete ulcer healing was achieved in 100% of the treatment group and 69% of the control group (p < 0.05). The Kaplan-Meier median times to complete closure were 35 and 57 days for the keratinocyte and control groups, respectively. No adverse events related to the treatment occurred. These results indicate that cultured allogeneic keratinocytes may offer a safe and effective treatment for diabetic foot ulcers. PMID- 22672335 TI - Shedding-generated Met receptor fragments can be routed to either the proteasomal or the lysosomal degradation pathway. AB - The receptor tyrosine kinase Met and its ligand, the hepatocyte growth factor/scatter factor, are essential for embryonic development, whereas deregulation of Met signaling pathways is associated with tumorigenesis and metastasis. The presenilin-regulated intramembrane proteolysis (PS-RIP) is involved in ligand-independent downregulation of Met. This proteolytic process involves shedding of the Met extracellular domain followed by gamma-secretase cleavage, generating labile intracellular fragments degraded by the proteasome. We demonstrate here that upon shedding both generated Met N- and C-terminal fragments are degraded directly in the lysosome, with C-terminal fragments escaping gamma-secretase cleavage. PS-RIP and lysosomal degradation are complementary, because their simultaneous inhibition induces synergistic accumulation of fragments. Met N-terminal fragments associate with the high affinity domain of HGF/SF, confirming its decoy activity which could be reduced through their routing to the lysosome at the expense of extracellular release. Finally, the DN30 monoclonal antibody inducing Met shedding promotes receptor degradation through induction of both PS-RIP and the lysosomal pathway. Thus, we demonstrate that Met shedding initiates a novel lysosomal degradation which participates to ligand-independent downregulation of the receptor. PMID- 22672336 TI - Risk factors affecting third molar autotransplantation in males: a retrospective survey in dental clinics. AB - The aim of this study was to investigate the risk factors affecting long-term prognosis of autotransplantation of third molars with complete root formation in males at dental clinics. Participating dentists were requested to provide information on transplantations they had undertaken from 1 January 1990 to 31 December 2010. Data on a total of 708 teeth from 637 patients were collected. After data screening and elimination, participants of this study consisted of 183 teeth of 171 males ranging from 20 to 72 years of age (mean age, 44.8 years). The cumulative survival rate was 86.0% at the 5-year mark, 59.1% at 10 years and 28.0% at 15 years. The mean survival time was 134.5 months, as calculated by the Kaplan-Meier method. Single factor analysis using the log-rank test showed that the following factors had significant influence (P < 0.05) on survival of transplanted teeth: periodontal disease as the reason for recipient site tooth extraction, fewer than 25 present teeth and Eichner index Groups B1 to C. Cox regression analysis examined five factors: age, smoking habit, recipient site extraction caused by periodontal disease, fewer than 25 present teeth and Eichner index. This analysis showed that two of these factors were significant: fewer than 25 present teeth was 2.63 (95% CI, 1.03-6.69) and recipient site extraction caused by periodontal disease was 3.80 (95% CI, 1.61-9.01). The results of this study suggest that long-term survival of transplanted teeth in males is influenced not only by oral bacterium but also by occlusal status. PMID- 22672338 TI - Malformation of gynoecia impedes fertilisation in bud-flowering Calluna vulgaris. AB - In Calluna vulgaris, a common bedding plant during autumn in the northern hemisphere, the bud-blooming mutation of flower morphology is of high economic importance. Breeding of new bud-blooming cultivars suffers from poor seed set in some of the desirable bud-flowering crossing partners. In the current study, fertilisation and seed development in genotypes with good or poor seed set were monitored in detail in order to examine pre- and post-zygotic cross breeding incompatibilities. Whereas no distinct differences were detected in seed development, pollen tube growth was impeded in the pistils of genotypes characterised by poor seed set. Detailed microscopic analysis revealed malformations of the gynoecia due to imperfect fusion of carpels. Hence, a pre zygotic mechanism hindering pollen tube growth due to malformation of gynoecia was deduced. An interaction of putative candidate genes involved in malformation of gynoecia with floral organ identity genes controlling the flower architecture is discussed. PMID- 22672337 TI - Borrelia burgdorferi malQ mutants utilize disaccharides and traverse the enzootic cycle. AB - Borrelia burgdorferi, the causative agent of Lyme disease, cycles in nature between a vertebrate host and a tick vector. We demonstrate that B. burgdorferi can utilize several sugars that may be available during persistence in the tick, including trehalose, N-acetylglucosamine (GlcNAc), and chitobiose. The spirochete grows to a higher cell density in trehalose, which is found in tick hemolymph, than in maltose; these two disaccharides differ only in the glycosidic linkage between the glucose monomers. Additionally, B. burgdorferi grows to a higher density in GlcNAc than in the GlcNAc dimer chitobiose, both of which may be available during tick molting. We have also investigated the role of malQ (bb0166), which encodes an amylomaltase, in sugar utilization during the enzootic cycle. In other bacteria, MalQ is involved in utilizing maltodextrins and trehalose, but we show that, unexpectedly, it is not needed for B. burgdorferi to grow in vitro on any of the sugars assayed. In addition, infection of mice by needle inoculation or tick bite, as well as acquisition and maintenance of the spirochete in the tick vector, does not require MalQ. PMID- 22672339 TI - Promoting social inclusion through Unified Sports for youth with intellectual disabilities: a five-nation study. AB - BACKGROUND: Although the promotion of social inclusion through sports has received increased attention with other disadvantaged groups, this is not the case for children and adults with intellectual disability who experience marked social isolation. The study evaluated the outcomes from one sports programme with particular reference to the processes that were perceived to enhance social inclusion. METHOD: The Youth Unified Sports programme of Special Olympics combines players with intellectual disabilities (called athletes) and those without intellectual disabilities (called partners) of similar skill level in the same sports teams for training and competition. Alongside the development of sporting skills, the programme offers athletes a platform to socialise with peers and to take part in the life of their community. Unified football and basketball teams from five countries--Germany, Hungary, Poland, Serbia and Ukraine- participated. Individual and group interviews were held with athletes, partners, coaches, parents and community leaders: totalling around 40 informants per country. RESULTS: Qualitative data analysis identified four thematic processes that were perceived by informants across all countries and the two sports to facilitate social inclusion of athletes. These were: (1) the personal development of athletes and partners; (2) the creation of inclusive and equal bonds; (3) the promotion of positive perceptions of athletes; and (4) building alliances within local communities. CONCLUSIONS: Unified Sports does provide a vehicle for promoting the social inclusion of people with intellectual disabilities that is theoretically credible in terms of social capital scholarship and which contains lessons for advancing social inclusion in other contexts. Nonetheless, certain limitations are identified that require further consideration to enhance athletes' social inclusion in the wider community. PMID- 22672340 TI - Current status of validation for robotic surgery simulators - a systematic review. AB - To analyse studies validating the effectiveness of robotic surgery simulators. The MEDLINE((r)), EMBASE((r)) and PsycINFO((r)) databases were systematically searched until September 2011. References from retrieved articles were reviewed to broaden the search. The simulator name, training tasks, participant level, training duration and evaluation scoring were extracted from each study. We also extracted data on feasibility, validity, cost-effectiveness, reliability and educational impact. We identified 19 studies investigating simulation options in robotic surgery. There are five different robotic surgery simulation platforms available on the market. In all, 11 studies sought opinion and compared performance between two different groups; 'expert' and 'novice'. Experts ranged in experience from 21-2200 robotic cases. The novice groups consisted of participants with no prior experience on a robotic platform and were often medical students or junior doctors. The Mimic dV-Trainer((r)), ProMIS((r)), SimSurgery Educational Platform((r)) (SEP) and Intuitive systems have shown face, content and construct validity. The Robotic Surgical SimulatorTM system has only been face and content validated. All of the simulators except SEP have shown educational impact. Feasibility and cost-effectiveness of simulation systems was not evaluated in any trial. Virtual reality simulators were shown to be effective training tools for junior trainees. Simulation training holds the greatest potential to be used as an adjunct to traditional training methods to equip the next generation of robotic surgeons with the skills required to operate safely. However, current simulation models have only been validated in small studies. There is no evidence to suggest one type of simulator provides more effective training than any other. More research is needed to validate simulated environments further and investigate the effectiveness of animal and cadaveric training in robotic surgery. PMID- 22672341 TI - Symptomatic subsegmental pulmonary embolism: what is the next step? AB - The introduction of computed tomography pulmonary angiography (CTPA) has led to an increase in the incidence of pulmonary embolism (PE) diagnosis. However, the case fatality rate is lower and the mortality rates of PE have remained unchanged, suggesting a lower severity of illness. Specifically, the multiple detector CTPA increased the rate of subsegmental filling defect reported in patients with suspected PE. Whether these filling defects reported on CTPA would correlate with true subsegmental PE (SSPE) on pulmonary angiography or are actually artifacts is unknown. The inter-observer agreement for SSPE diagnosis among radiologists with varied levels of experience is low (kappa of 0.38; 95% CI, 0.0-0.89). Furthermore, the clinical importance of a symptomatic SSPE diagnosed by CTPA is unclear. SSPE are frequent on pulmonary angiography in patients with a low probability ventilation-perfusion (V/Q) scan for suspected PE. Several prospective management cohort studies have demonstrated that patients with low or intermediate V/Q scan results can be safely managed without anticoagulation by combining the scan results with the pretest probability (PTP) of PE and compression ultrasonography. Although clinical equipoise exists, the majority of patients diagnosed with SSPE on CTPA are currently treated with anticoagulant therapy. Only a small number of patients with SSPE diagnosed by CTPA and without DVT who did not receive anticoagulation treatment have been reported in the literature. None of these patients suffered recurrent symptomatic VTE (PE or DVT) during the 3-month follow-up period (0%; 95% CI, 0-7.4%), suggesting that SSPE might be clinically unimportant. These conclusions are only hypothesis generating and need to be confirmed in prospective clinical management studies before changing clinical practice. PMID- 22672343 TI - Postprandial insulin resistance in Zucker diabetic fatty rats is associated with parasympathetic-nitric oxide axis deficiencies. AB - The Zucker diabetic fatty (ZDF) rat is an obesity and type 2 diabetes model. Progression to diabetes is well characterised in ZDF rats, but only in the fasted state. We evaluated the mechanisms underlying postprandial insulin resistance in young ZDF rats. We tested the hypothesis that the overall postprandial action of insulin is affected in ZDF rats as a result of impairment of the hepatic parasympathetic-nitric oxide (PSN-NO) axis and/or glutathione (GSH), resulting in decreased indirect (PSN-NO axis) and direct actions of insulin. Nine-week-old male ZDF rats and lean Zucker rats (LZR, controls) were used. The action of insulin was assessed in the fed state before and after parasympathetic antagonism atropine. Basal hepatic NO and GSH were measured, as well as NO synthase (NOS) and gamma-glutamyl-cysteine synthethase (GCS) activity and expression. ZDF rats presented postprandial hyperglycaemia (ZDF, 201.4 +/- 12.9 mg/dl; LZR, 107.7 +/- 4.3 mg/dl), but not insulinopaenia (ZDF, 5.9 +/- 0.8 ng/ml; LZR, 1.5 +/- 0.3 ng/ml). Total postprandial insulin resistance was observed (ZDF, 78.6 +/- 7.5 mg glucose/kg; LZR, 289.2 +/- 24.7 mg glucose/kg), with a decrease in both the direct action of insulin (ZDF, 54.8 +/- 7.0 mg glucose/kg; LZR, 173.3 +/- 20.5 mg glucose/kg) and the PSN-NO axis (ZDF, 24.5 +/- 3.9 mg glucose/kg; LZR, 115.9 +/- 19.4 mg glucose/kg). Hepatic NO (ZDF, 117.2 +/- 11.4 MUmol/g tissue; LZR, 164.6 +/- 4.9 MUmol/g tissue) and GSH (ZDF, 4.9 +/- 0.3 MUmol/g; LZR, 5.9 +/- 0.2 MUmol/g) were also compromised as a result of decreased NOS and GCS activity, respectively. These results suggest a compromise of the mechanism responsible for potentiating insulin action after a meal in ZDF rats. We show that defective PSN NO axis and GSH synthesis, together with an impaired direct action of insulin, appears to contribute to postprandial insulin resistance in this model. PMID- 22672344 TI - Is MRI better than CT for detecting a vascular component to dementia? A systematic review and meta-analysis. AB - BACKGROUND: Identification of causes of dementia soon after symptom onset is important, because appropriate treatment of some causes of dementia can slow or halt its progression or enable symptomatic treatment where appropriate. The accuracy of MRI and CT, and whether MRI is superior to CT, in detecting a vascular component to dementia in autopsy confirmed and clinical cohorts of patients with VaD, combined AD and VaD ("mixed dementia"), and AD remain unclear. We conducted a systematic review and meta-analysis to investigate this question. METHODS: We searched eight databases and screened reference lists to identify studies addressing the review question. We assessed study quality using QUADAS. We estimated summary diagnostic accuracy according to imaging finding, and ratios of diagnostic odds ratios (RDORs) for MRI versus CT and high versus low risk of bias. RESULTS: We included 7 autopsy and 31 non-autopsy studies. There was little evidence that selective patient enrolment and risk of incorporation bias impacted on diagnostic accuracy (p = 0.12 to 0.95). The most widely reported imaging finding was white matter hyperintensities. For CT (11 studies) summary sensitivity and specificity were 71% (95% CI 53%-85%) and 55% (44%-66%). Corresponding figures for MRI (6 studies) were 95% (87%-98%) and 26% (12%-50%). General infarcts was the most specific imaging finding on MRI (96%; 95% CI 94% 97%) and CT (96%; 93%-98%). However, sensitivity was low for both MRI (53%; 36% 70%) and CT (52%; 22% to 80%). No imaging finding had consistently high sensitivity. Based on non-autopsy studies, MRI was more accurate than CT for six of seven imaging findings, but confidence intervals were wide. CONCLUSION: There is insufficient evidence to suggest that MRI is superior to CT with respect to identifying cerebrovascular changes in autopsy-confirmed and clinical cohorts of VaD, AD, and 'mixed dementia'. PMID- 22672345 TI - Visuomotor gain distortion alters online motor performance and enhances primary motor cortex excitability in patients with stroke. AB - OBJECTIVES: Determine if ipsilesional primary motor cortex (M1) in stroke patients processes online visuomotor discordance in gain between finger movement and observed feedback in virtual reality (VR). MATERIALS AND METHODS: Chronic stroke patients flexed (N= 7) or extended (N= 1) their finger with real-time feedback of a virtual hand presented in VR. Virtual finger excursion was scaled by applying a low-gain (G(0.25) ), high-gain (G(1.75) ), or veridical (G(1.00) ) scaling factor to real-time data streaming from a sensor glove. Effects of visuomotor discordance were assessed through analysis of movement kinematics (joint excursion, movement smoothness, and angular velocity) and amplitude of motor evoked potentials (MEPs) elicited with transcranial magnetic stimulation applied to ipsilesional M1. Data were analyzed with a repeated-measures analysis of variance (significance set at 0.05). RESULTS: G(0.25) discordance (relative to veridical) leads to significantly larger joint excursion, online visuomotor correction evidenced by decreased trajectory smoothness, and significantly facilitated agonist MEPs. This effect could not be explained by potential differences in motor drive (background electromyographic) or by possible differences related to joint angle or angular velocity, as these variables remained invariant across conditions at the time of MEP assessment. M1 was not significantly facilitated in the G(1.75) condition. MEPs recorded in an adjacent muscle that was not involved in the task were unaffected by visual feedback in either discordance condition. These data suggest that the neuromodulatory effects of visuomotor discordance on M1 were relatively selective. CONCLUSIONS: Visuomotor discordance may be used to alter movement performance and augment M1 excitability in patients following stroke. Our data illustrate that visual feedback may be a robust way to selectively modulate M1 activity. These data may have important clinical implications for the development of future VR training protocols. PMID- 22672346 TI - Simultaneous total corporal reconstruction and implantation of a penile prosthesis in patients with erectile dysfunction and severe fibrosis of the corpora cavernosa. AB - INTRODUCTION: Implantation of a penile prosthesis in severely scarred corporal bodies represents a great challenge as fibrosis can compromise dilatation and subsequent closure of the corpora cavernosa and limit size, type, and function of the device. AIM: The aim of this study is to report our experience of simultaneous corporeal reconstruction and penile prosthesis implantation in patients with severe penile contracture consequence of diffuse fibrosis. METHODS: Between March 2006 and February 2010, 18 patients with severe penile contracture and coporeal fibrosis underwent simultaneous corporeal reconstruction and placement of a penile prosthesis. MAIN OUTCOME MEASURES: Surgical outcome and complications have been recorded during postoperative follow-up. Patients' satisfaction has been assessed 6 months postoperatively with the administration of the modified erectile dysfunction index of treatment satisfaction questionnaire. RESULTS: Although the dilatation of the corpora was extremely difficult due to the severe fibrosis, a penile prosthesis has been implanted in all patients. A malleable penile prosthesis has been inserted in four patients and a three-piece inflatable device in the remainder. After an average follow-up of 26 months (range 6-36), revision surgery was required in four patients (elective exchange to three-piece inflatable device in three patients and upsizing of the implant in one patient). Although all patients were able to achieve penetrative sexual intercourse, four patients were partially dissatisfied because of significant penile shortening. CONCLUSION: In expert hands, simultaneous penile prosthesis implantation and corporal reconstruction of severely scarred corpora yield satisfactory results. Patients must be warned that complication rate in presence of severe fibrosis is significantly higher than in virgin cases and that downsized cylinders might be required due to the contracture of the tunica albuginea. PMID- 22672347 TI - Development and validation of a real-time PCR assay for detection and quantification of Tuber magnatum in soil. AB - BACKGROUND: Tuber magnatum, the Italian white truffle, is the most sought-after edible ectomycorrhizal mushroom. Previous studies report the difficulties of detecting its mycorrhizas and the widespread presence of its mycelium in natural production areas, suggesting that the soil mycelium could be a good indicator to evaluate its presence in the soil. In this study a specific real-time PCR assay using TaqMan chemistry was developed to detect and quantify T. magnatum in soil. This technique was then applied to four natural T. magnatum truffieres located in different regions of Italy to validate the method under different environmental conditions. RESULTS: The primer/probe sets for the detection and quantification of T. magnatum were selected from the ITS rDNA regions. Their specificity was tested in silico and using qualitative PCR on DNA extracted from 25 different fungal species. The T. magnatum DNA concentration was different in the four experimental truffieres and higher in the productive plots. T. magnatum mycelium was however also detected in most of the non-productive plots. Ascoma production during the three years of the study was correlated with the concentration of T. magnatum DNA. CONCLUSIONS: Taken together, these results suggest that the specific real-time PCR assay perfected in this study could be an useful tool to evaluate the presence and dynamics of this precious truffle in natural and cultivated truffieres. PMID- 22672349 TI - Management and risk factors for mortality in very elderly patients with acute myocardial infarction. AB - AIM: Elderly patients often remain underrepresented in clinical trials. The aim of our study was to analyze the treatment, clinical outcome and risk factors for mortality in patients aged >=85 years with ST-segment elevation myocardial infarction (STEMI). METHODS: From 2005-2011, 102 patients aged >=85 years with STEMI admitted to a coronary care unit were retrospectively reviewed. Clinical data, treatment and outcome were recorded. Reperfusion strategy and its influence in hospital morbidity and mortality were evaluated. Morbidity was defined as the presence of heart failure (Killip-Kimball >1), arrhythmias, mechanical complications, stroke or major bleeding. Risk factors for mortality were assessed by multivariate analysis. RESULTS: The mean age was 87.5+/-2.5 years (range 85 96). Therapeutic strategy on admission was: primary-angioplasty (PCI) for 33 patients (32.3%) fibrinolysis for 30 patients (29.4%) and conservative treatment for 35 patients (34.3%). In the four remaining patients, rescue angioplasty was required. A total of 29 patients (28.4%) died, and morbidity was seen in 63 patients (61.7%). The morbidity and mortality rates in the conservative treatment group (77.1% and 48.5%) were higher than that found in the reperfusion strategy group (primary-PCI and fibrinolysis; 53.7% and 17.9%; P=0.02 and P=0.002, respectively). Regarding mortality, the univariate analysis showed that heart failure on admission (P=0.0001) and previous coronary artery disease (P=0.01) were prognostic variables. Only heart failure was an independent risk factor for mortality (odds ratio=3.64, 95% CI 0.78-21.87, P<0.0001). CONCLUSIONS: Mortality and morbidity in very elderly patients with STEMI are very high, especially in those not receiving reperfusion therapies. Heart failure on admission was an independent risk factor for hospital mortality. PMID- 22672348 TI - Within-patient variation of hemoglobin and reticulocytes: implications for evaluating ESA responsiveness in dialysis patients. AB - INTRODUCTION: Techniques that assess percent reticulocytes (%retics) or hemoglobin (Hb) to detect erythropoiesis-stimulating agents (ESA) use in athletes may be useful in evaluating ESA responsiveness in dialysis patients. However, within-patient variation, appropriate transformation, or the relationship between the blood draw interval length and analyte variation are untested. METHODS: In a prospective, single-arm trial, we determined Hb and %retics in 30 hemodialysis patients receiving stable ESA doses. Within-patient results were evaluated for variance homogeneity and normality with and without transformation. RESULTS: Square-root transformation (sqrt) of %retics produced the most constant variance (lowest r-value for correlation between sqrt|normalized residuals| and fitted values: 0.018 highest P-value 0.739) compared with log transformation (r = 0.198, P < 0.001) or no transformation (r = 0.215, P < 0.001) and showed the least departure from normality (highest P-value: 0.002 vs. < 0.001 vs. < 0.001, respectively). Hb results did not improve with transformation. Within-patient variance in both %retics and Hb increased with interval length between lab draws (P < 0.001). CONCLUSIONS: Initial assessment of anti-doping tool use in dialysis patient anemia management indicates square-root transformation of %retics and adjustment for time between lab draw intervals for both %retics and Hb will be required. PMID- 22672350 TI - Prediction of significant conduction disease through noninvasive assessment of cardiac calcification. AB - AIMS: Cardiac calcification is associated with coronary artery disease, arrhythmias, conduction disease, and adverse cardiac events. Recently, we have described an echocardiographic-based global cardiac calcification scoring system. The objective of this study was to evaluate the severity of cardiac calcification in patients with permanent pacemakers as based on this scoring system. METHODS AND RESULTS: Patients with a pacemaker implanted within the 2-year study period with a previous echocardiogram were identified and underwent blinded global cardiac calcium scoring. These patients were compared to matched control patients without a pacemaker who also underwent calcium scoring. The study group consisted of 49 patients with pacemaker implantation who were compared to 100 matched control patients. The mean calcium score in the pacemaker group was 3.3 +/- 2.9 versus 1.8 +/- 2.0 (P = 0.006) in the control group. Univariate and multivariate analysis revealed glomerular filtration rate and calcium scoring to be significant predictors of the presence of a pacemaker. CONCLUSION: Echocardiographic-based calcium scoring correlates with the presence of severe conduction disease requiring a pacemaker. PMID- 22672351 TI - Emergence of biopharmaceutical innovators in China, India, Brazil, and South Africa as global competitors and collaborators. AB - Biopharmaceutical innovation has had a profound health and economic impact globally. Developed countries have traditionally been the source of most innovations as well as the destination for the resulting economic and health benefits. As a result, most prior research on this sector has focused on developed countries. This paper seeks to fill the gap in research on emerging markets by analyzing factors that influence innovative activity in the indigenous biopharmaceutical sectors of China, India, Brazil, and South Africa. Using qualitative research methodologies, this paper a) shows how biopharmaceutical innovation is taking place within the entrepreneurial sectors of these emerging markets, b) identifies common challenges that indigenous entrepreneurs face, c) highlights the key role played by the state, and d) reveals that the transition to innovation by companies in the emerging markets is characterized by increased global integration. It suggests that biopharmaceutical innovators in emerging markets are capitalizing on opportunities to participate in the drug development value chain and thus developing capabilities and relationships for competing globally both with and against established companies headquartered in developed countries. PMID- 22672352 TI - Inhibition of melanogenesis and antioxidant properties of Magnolia grandiflora L. flower extract. AB - BACKGROUND: Magnolia grandiflora L. flower is wildly used in Asian as a traditional herbal medication. The purpose of the study was to investigate the antimelanogenic and antioxidant properties of Magnolia grandiflora L. flower extract. In the study, the inhibitory effects of M. grandiflora L. flower extract on mushroom tyrosinase, B16F10 intracellular tyrosinase activity and melanin content were determined spectrophotometrically. Meanwhile, the antioxidative capacity of the flower extract was also investigated. RESULTS: Our results revealed that M. grandiflora L. flower extract inhibit mushroom tyrosinase activity (IC(50) = 11.1%; v/v), the flower extract also effectively suppressed intracellular tyrosinase activity (IC(50) = 13.6%; v/v) and decreased the amount of melanin (IC(50) = 25.6%; v/v) in a dose-dependent manner in B16F10 cells. Protein expression level of tyrosinase and tyrosinase-related protein 1 (TRP-1) were also decreased by the flower extract. Additionally, antioxidant capacities such as ABTS(+) free radical scavenging activity, reducing capacity and total phenolic content of the flower extract were increased in a dose-dependent pattern. CONCLUSIONS: Our results concluded that M. grandiflora L. flower extract decreased the expression of tyrosinase and TRP-1, and then inhibited melanogenesis in B16F10 cells. The flower extract also show antioxidant capacities and depleted cellular reactive oxygen species (ROS). Hence, M. grandiflora L. flower extract could be applied as a type of dermatological whitening agent in skin care products. PMID- 22672353 TI - Deep and superficial masseter muscle blood flow in women. AB - PURPOSE: Although changes in blood perfusion have been described as being associated with temporomandibular disorder (TMD) myofascial pain, very little is known about blood flow levels in the deep and superficial masseter muscle. This study investigated blood flow in deep and superficial sites of six healthy female participants at baseline and during intermittent and continuous biting exercises and recovery. MATERIALS AND METHODS: Blood flow was monitored unilaterally using a single-fiber probe laser Doppler flowmeter. The blood flow was continuously monitored at baseline and during two biting exercises: (a) intermittent at 25%, 50%, and 100% maximum voluntary bite force for 30 seconds each followed by 90 seconds rest between each biting level and (b) continuous biting at similar maximum voluntary bite force levels followed by 90 seconds rest. RESULTS: There was significantly higher blood flow in the deep sites compared to the superficial sites (p < 0.001) and a significant increase in blood flow during biting compared to baseline (p < 0.001). There were no significant changes in blood flow among the three levels of biting, between the intermittent and continuous exercises, or from baseline blood flow compared to recovery. CONCLUSIONS: This study showed regional differences in masseter muscle blood flow, perhaps related to differences in muscle fiber type and pattern of muscle fiber recruitment. PMID- 22672354 TI - Revising acute care systems and processes to improve breastfeeding and maternal postnatal health: a pre and post intervention study in one English maternity unit. AB - BACKGROUND: Most women in the UK give birth in a hospital labour ward, following which they are transferred to a postnatal ward and discharged home within 24 to 48 hours of the birth. Despite policy and guideline recommendations to support planned, effective postnatal care, national surveys of women's views of maternity care have consistently found in-patient postnatal care, including support for breastfeeding, is poorly rated. METHODS: Using a Continuous Quality Improvement approach, routine antenatal, intrapartum and postnatal care systems and processes were revised to support implementation of evidence based postnatal practice. To identify if implementation of a multi-faceted QI intervention impacted on outcomes, data on breastfeeding initiation and duration, maternal health and women's views of care, were collected in a pre and post intervention longitudinal survey. Primary outcomes included initiation, overall duration and duration of exclusive breastfeeding. Secondary outcomes included maternal morbidity, experiences and satisfaction with care. As most outcomes of interest were measured on a nominal scale, these were compared pre and post intervention using logistic regression. RESULTS: Data were obtained on 741/1160 (64%) women at 10 days post-birth and 616 (54%) at 3 months post-birth pre-intervention, and 725/1153 (63%) and 575 (50%) respectively post-intervention. Post intervention there were statistically significant differences in the initiation (p = 0.050), duration of any breastfeeding (p = 0.020) and duration of exclusive breastfeeding to 10 days (p = 0.038) and duration of any breastfeeding to three months (p = 0.016). Post intervention, women were less likely to report physical morbidity within the first 10 days of birth, and were more positive about their in-patient care. CONCLUSIONS: It is possible to improve outcomes of routine in-patient care within current resources through continuous quality improvement. PMID- 22672355 TI - Identifying poor performance among doctors in NHS organizations. AB - AIM: To account for the means by which poor performance among career doctors is identified by National Health Service organizations, whether the tools are considered effective and how these processes may be strengthened in the light of revalidation and the requirement for doctors to demonstrate their fitness to practice. METHOD: This study sought to look beyond the 'doctor as individual'; as well as considering the typical approaches to managing the practice of an individual, the systems within which the doctor is working were reviewed, as these are also relevant to standards of performance. A qualitative review was undertaken consisting of a literature review of current practice, a policy review of current documentation from 15 trusts in one deanery locality, and 14 semi structured interviews with respondents with an overview of processes in use. The framework for the analysis of the data considered tools at three levels: individual, team and organizational. RESULTS: Tools are, in the main, reactive- with an individual focus. They rely on colleagues and others to speak out, so their effectiveness is hindered by a reluctance to do so. Tools can lack an evidence base for their use, and there is limited linking of data across contexts and tools. CONCLUSIONS: There is more work to be done in evaluating current tools and developing stronger processes. Linkage between data sources needs to be improved and proactive tools at the organizational level need further development to help with the early identification of performance issues. This would also assist in balancing a wider systems approach with a current over emphasis on individual doctors. PMID- 22672356 TI - Coronary angioplasty and the internet: what can patients searching online expect to find? AB - OBJECTIVES: This study set out to assess the quality of online information available on coronary angioplasty. BACKGROUND: Patients searching for healthcare information frequently use the Internet. However the lay reader may not be able to discern the robustness of evidence presented. At present, the overall quality and accuracy of online content regarding coronary angioplasty is unknown. METHODS: The search term "coronary angioplasty" was entered into three popular search engines (Google, Yahoo, and Bing), and the first 50 webpages provided by each search engine pooled. Exclusion criteria consisted of duplicated sites, sites requiring a registration or login, and direct links to documents or videos. The remaining sites were analyzed using the LIDA instrument; a validated method for assessing websites based on accessibility, usability, and readability. Readability was also separately assessed using the Flesch Reading Ease Score (FRES). RESULTS: Of 150 weblinks reviewed, 86 were excluded on the basis of the criteria listed above. The remaining 64 sites achieved mean scores of 50/60 (83%) on accessibility, 40/54 (74%) on usability, 32/51 (62%) on reliability, and 47.5 on FRES. Significant variability was noted among the LIDA scores, with no correlation between LIDA score and search engine ranking. CONCLUSIONS: Although most websites are easy to access, content is frequently out-of-date and fails to be presented in an easily comprehensible format. A minority of websites display factually incorrect information. Clinicians should be wary of patients being misled by erroneous or commercially biased online content, and be able to redirect their patients to more robust, up-to-date sources. PMID- 22672357 TI - Capturing skin properties from dynamic mechanical analyses. AB - BACKGROUND/PURPOSE: Existing skin mechanical testing devices focus on measuring skin elasticity and are not tailored to assess the dynamic behavior of skin. Additionally, the mathematical techniques used in existing devices are often not optimal. METHODS: A new dynamic mechanical device that measures the linear dynamics of skin was developed and tested. The mechanical properties of skin were evaluated in experiments in which stiffness and damping parameters were measured (i) at different locations on the arm and hand, (ii) when stratum corneum hydration was varied by controlled changes in environmental humidity, and (iii) following the application of film-forming polymers. Parallel measurements were made with the Cutometer so that the two devices could be compared. RESULTS: The findings revealed that reliable and valid measurements of skin mechanical properties can be obtained from the device. The stiffness of the skin was shown to vary significantly as a function of skin site, changes in stratum corneum hydration and following application of the polymer films. Changes in the damping parameter were less consistently associated with varying the condition of the skin. CONCLUSION: The high reliability and speed of measurement make this device and analytic procedure an attractive option for testing skin mechanics. PMID- 22672359 TI - Effects of a laughter and exercise program on physiological and psychological health among community-dwelling elderly in Japan: randomized controlled trial. AB - AIM: To examine the effects of a once-weekly laughter and exercise program on physical and psychological health among elderly people living in the community. As a regular exercise program can be difficult to maintain, we provided a more enjoyable program to enhance adherence to exercise. METHODS: A total of 27 individuals aged 60 years or older, without disabilities, were randomly assigned to either an immediate treatment group (n=14) or a delayed treatment group (n=13). The intervention was a 120-min session consisting of laughter and exercise, carried out once a week for 10 consecutive weeks. Measurements taken at baseline, 3 and 6 months included bodyweight, height, body fat, lean mass, bone mineral density, hemoglobin A1c (HbA(1c)), glucose, high-density lipoprotein and low-density lipoprotein cholesterol, and triglycerides, as well as self-rated health and psychological factors. RESULTS: All participants completed the 3-month program. Bone mineral density increased significantly in the immediate treatment group compared with the delayed treatment group during the first 3 months (P<0.001). In addition, HbA(1c) decreased significantly (P=0.001), and self-rated health increased significantly (P=0.012). CONCLUSIONS: The combination of a laughter and exercise program might have physiological and psychological health benefits for the elderly. Laughter might be an effective strategy to motivate the elderly to participate in physical activity. PMID- 22672358 TI - The Italian information system on zoonoses data collection. AB - In the framework of the international obligations subscribed by the Italian government, the Italian Ministry of Health should provide the European Union (EU) (European Commission, European Food Safety Authority - EFSA) with a set of data and information related to the report and the spread of zoonoses and to the activities put in place for monitoring and control of zoonoses. In 2008, the Italian Ministry of Health commissioned the Istituto G. Caporale (ICT) to implement an information system able to provide information and data on the monitoring and control of zoonoses in the national territory, in accordance with the national and community legislation. The system is part of the e-Government process that involves all public administrations of the EU and refers to the use of information and communication technologies for the digital processing of documents in order to obtain simplification and interoperability of administrative procedures through the Internet, as defined in the strategic lines published by the National Centre for Information Systems in Public Administration (DigitPA) in 2009-2011. PMID- 22672360 TI - Overexpression of high mobility group box 1 with poor prognosis in patients after radical prostatectomy. AB - What's known on the subject? and What does the study add? Recent studies have indicated that high mobility group box 1 (HMGB1) is related to the development and progression of human carcinomas. However, further studies were required to confirm the roles played by HMGB1 in clinical prostate cancer treatment. We investigated the relationship between HMGB1 expression and the characteristics of prostate cancer, and also evaluated the significance of HMGB1 as a prognostic factor for biochemical recurrence-free survival after radical prostatectomy. OBJECTIVE: * To investigate high mobility group box 1 (HMGB1) expression in human prostate cancer (PC) cell lines and its prognostic significance after radical prostatectomy (RP). PATIENTS AND METHODS: * Quantitative reverse-transcription polymerase chain reaction and western blotting were used to detect HMGB1 mRNA and protein expression in PC cell lines. * Immunohistochemistry coupled with the tissue microarray technique was performed to evaluate HMGB1 protein expression in 168 primary prostatectomy tissue samples. * Clinicopathological features were compared between positive and negative HMGB1 protein expression groups. * Kaplan Meier and multivariate Cox analyses were applied to determine the prognostic value of HMGB1 protein expression on biochemical recurrence (BCR) for patients with PC who were undergoing RP. RESULTS: * There were three PC cells (DU145, PC-3 and LNCaP) with overexpression of HMGB1 mRNA and protein compared to the non transformed immortalized prostate cell RWPE-1. * A total of 60.1% (101/168) of the PC samples appeared to have positive protein expression of HMGB1. * HMGB1 protein expression was correlated with some clinicopathological parameters, such as pathological stage (pT) (P= 0.011), Gleason score, preoperative prostate specific antigen concentration and BCR (P < 0.001, respectively). * Positive HMGB1 immunostaining in patients with PC who were undergoing RP was significantly associated with poor median BCR-free survival (23.1 months vs 15.6 months) (P < 0.001). * Multivariate analysis indicated that HMGB1 protein expression was an independent prognostic factor for BCR-free survival after RP (hazard ratio = 2.348, 95% confidence interval = 1.373-6.361, P= 0.001). CONCLUSIONS: * Up regulation of HMGB1 mRNA and protein concentrations was confirmed in PC cells. * HMGB1 expression may contribute to the malignant progression of PC. * HMGB1 presents as a novel prognostic factor for BCR after RP. PMID- 22672361 TI - Behavioural changes and occlusal splints are effective in the management of masticatory myofascial pain: a short-term evaluation. AB - The aim of this research was to test the hypothesis that treatment with intra oral appliances with different occlusal designs was beneficial in the management of pain of masticatory muscles compared with a control group. A total of 51 patients were analysed according to the research diagnostic criteria for temporomandibular disorders (RDC/TMD) to obtain the diagnosis of masticatory myofascial pain (MMP). The sample was then randomly divided into three groups: group I (n = 21) wore a full coverage acrylic stabilisation occlusal splint; group II (n = 16) wore an anterior device nociceptive trigeminal inhibitory (NTI) system; and group III (n = 14) only received counselling for behavioural changes and self-care (the control group). The first two groups also received counselling. Follow-ups were performed after 2 and 6 weeks and 3 months. In these sessions, patients were evaluated by means of a visual analogue scale (VAS) and pressure pain threshold (PPT) of the masticatory muscles. Possible adverse effects were also recorded, such as discomfort while using the appliance and occlusal changes. The results were analysed with Kruskal-Wallis, anova, Tukey's and Friedman tests, with a significance level of 5%. Group I showed improvement in the reported pain at the first follow-up (2 weeks), whereas for groups II and III, this progress was detected only after 6 weeks and 3 months, respectively. The PPT values did not change significantly. It was concluded that behavioural changes are effective in the management of pain in MMP patients. However, the simultaneous use of occlusal devices appears to produce an earlier improvement. PMID- 22672362 TI - Construction of a traditional Chinese medicine syndrome-specific outcome measure: the Kidney Deficiency Syndrome Questionnaire (KDSQ). AB - BACKGROUND: Development of Traditional Chinese Medicine (TCM) syndrome-specific outcome measures is needed for the evaluation of TCM syndrome-specific therapies. We constructed a Kidney Deficiency Syndrome Questionnaire (KDSQ) for the evaluation of the common TCM syndromes Kidney-Yin Deficiency Syndrome (KDS-Yin) and Kidney-Yang Deficiency Syndrome (KDS-Yang) in middle-aged women with menopausal symptoms. METHODS: KDS-Yin and KDS-Yang were traditionally defined by expert opinion were validated by exploratory factor analysis (EFA) and structural equation modeling (SEM). Content validity was tested by EFA on a sample of 236 women from a seminar and SEM on another sample of 321 women from a postal survey. Other psychometric properties were tested on 292 women from the seminar at baseline and two systematically selected sub-samples: 54 who reported no changes in discomforts 11-12 days after the baseline and 31 who reported changes in discomforts 67-74 days after the baseline. All participants completed the KDSQ, the Greene Climacteric Scale and the standard 12-item Short Form Health Survey. RESULTS: The EFA and SEM established the measurement models of KDS-Yin and KDS Yang supporting content validity of the KDSQ. Internal consistency was good (Cronbach's Alpha >0.70). Construct validity was supported by theoretically derived levels of correlation with the established external measures. Test-retest reliability was strong (ICC(agreement): KDS-Yin, 0.94; KDS-Yang, 0.93). The KDSQ was responsive to changes over time as tested by effect size and longitudinal validity. CONCLUSIONS: The KDSQ was a valid and reliable measure for KDS-Yin and KDS-Yang in Hong Kong Chinese middle-aged women with menopausal symptoms. PMID- 22672363 TI - Diet components associated with perceived fatigue in breast cancer survivors. AB - Little is known about the contribution of diet components independent of body composition to persistent fatigue in breast cancer survivors. Therefore, our study aim was to determine the associations among dietary intake and fatigue in relation to and independent of adiposity and physical activity (PA) in breast cancer survivors. Baseline data from 42 breast cancer survivors enrolled in a randomised exercise trial were analysed: fatigue (Functional Assessment of Cancer Therapy for fatigue), diet components (3-day diet record), body mass index, per cent body fat (dual-energy X-ray absorptiometry) and PA (accelerometer). The mean age was 54 +/- 9 years with an average body mass index of 30.5 +/- 8.1 kg/m(2). Fatigue was positively associated with % of kcal/day fat intake (r = 0.31, P < 0.05) and inversely related to fibre g/day (r = 0.38, P < 0.05) and carbohydrate g/day intake (r = 0.31, P < 0.05). Mean fatigue was greater for participants eating <25 g/day of fibre compared with >25 g/day of fibre (15.7 +/- 10.8 versus 6.4 +/- 3.7, P < 0.005). No significant associations were noted between fatigue and PA or body composition. Diets high in fibre and low in fat are associated with reduced fatigue in breast cancer survivors. The difference in fatigue for low- versus high-fibre diets exceeded the minimal clinically important difference of three units. Prospective studies evaluating the effect of changing diet on fatigue in breast cancer survivors are warranted. PMID- 22672364 TI - Percutaneous implanted paddle lead for spinal cord stimulation: technical considerations and long-term follow-up. AB - OBJECTIVES: Spinal cord stimulation (SCS) is an established method for treatment of chronic pain. Cylindrical-type leads can be implanted percutaneously. In contrast, paddle leads (lamitrode) require more invasive surgery (i.e., laminotomy or laminectomy) for placement into the epidural space, thereby offering several advantages over percutaneous leads (octrode), including less lead migration and better paresthesia coverage. The goal of this study was to prospectively demonstrate the safety and efficacy of a percutaneous paddle lead for SCS. MATERIALS AND METHODS: This prospective trial enrolled 81 patients. The mean age was 57 years (range 27-82 years) with an almost equal sex distribution (male 47%, female 53%). Most patients (90%) had failed back surgery syndrome combined with lower extremity pain and lower back pain. A percutaneous paddle lead was implanted using a novel introduction system for percutaneous implantation. All implantations were performed under local anesthesia. Prior to the final implantation of the impulse generator, all patients underwent seven days of trial stimulation with pain assessment using a visual analog scale (VAS). The median follow-up was 12 months. RESULTS: The data showed favorable clinical outcomes for paresthesia coverage and pain reduction (median VAS 8.4 vs. 2.3), with a risk profile comparable with known percutaneous techniques. Compared with the published data (2-22%), the lead migration rate in this study was low (2.5%). No perioperative complications occurred. CONCLUSIONS: This new, minimally invasive percutaneous paddle lead is effective and safe, with a low migration rate. Placement can be done under local anesthesia, allowing an intraoperative assessment of the paresthesia coverage in terms of pain relief. This approach is less invasive and offers a faster and more comfortable procedure compared with laminotomy or laminectomy. PMID- 22672365 TI - International collaboration as a tool for diagnosis of patients with inherited thrombocytopenia in the setting of a developing country. AB - BACKGROUND: Inherited thrombocytopenias (ITs) are heterogeneous genetic disorders that frequently represent a diagnostic challenge. The requirement of highly specialized tests for diagnosis represents a particular problem in resource limited settings. To overcome this difficulty, we applied a diagnostic algorithm and developed a collaboration program with a specialized international center in order to increase the diagnostic yield in a cohort of patients in Argentina. METHODS: Based on the algorithm, initial evaluation included collection of clinical data, platelet size, blood smear examination and platelet aggregation tests. Confirmatory tests were performed according to diagnostic suspicion, which included platelet glycoprotein expression, immunofluorescence for myosin-9 in granulocytes and platelet thrombospondin-1 and molecular screening of candidate genes. RESULTS: Thirty-one patients from 14 pedigrees were included; their median age was 32 (4-72) years and platelet count 72 (4-147)*10(9) L(-1). Autosomal dominant inheritance was found in nine (64%) pedigrees; 10 (71%) had large platelets and nine (29%) patients presented with syndromic forms. A definitive diagnosis was made in 10 of 14 pedigrees and comprised MYH9-related disease in four, while classic and monoallelic Bernard-Soulier syndrome, gray platelet syndrome, X-linked thrombocytopenia, thrombocytopenia 2 (ANKRD26 mutation) and familial platelet disorder with predisposition to acute myelogenous leukemia were diagnosed in one pedigree each. CONCLUSIONS: Adoption of an established diagnostic algorithm and collaboration with an expert referral center proved useful for diagnosis of IT patients in the setting of a developing country. This initiative may serve as a model to develop international networks with the goal of improving diagnosis and care of patients with these rare diseases. PMID- 22672366 TI - Comparison of left ventricular stroke volume assessment by two- and three dimensional echocardiography in a swine model of acute myocardial infarction validated by thermodilution method. AB - BACKGROUND: Accurate left ventricular stroke volume (LVSV) measurement is clinically important in patients presenting with acute myocardial infarction. Three-dimensional echocardiography (3DE) is expected to overcome limitations of two-dimensional echocardiography (2DE). However, inaccuracy in volumetry by 3DE has often been reported hindering further clinical application. This study aimed at comparing agreement and correlation with the thermodilution method (TDM) between 2DE and 3DE measurement of LVSV. METHODS: Swine model of myocardial infarction was created and LVSV was measured by 3DE by subtracting end-systolic from end-diastolic volume (3DE-method). Pulsed Doppler ultrasound and left ventricular outlet tract area were used to measure LVSV by 2DE (2DE-method). TDM was performed by the Swan-Ganz catheter. Bland-Altman analysis followed by assessment of intraclass correlation coefficient (ICC) were performed between 2DE method and TDM as well as 3DE-method and TDM. RESULTS: A total of 25 comparisons revealed a significant overestimation of LVSV by the 2DE-method (bias = 6.5 mL; 95% confidence interval [CI], 3.9-9.0 mL; P < 0.0001), whereas there was no significant bias by the 3DE-method (bias =-1.6; 95% CI, -4.3 to 1.1 mL; P = 0.22). The ICC between 2DE and TDM was 0.49 (95% CI, 0.14-0.74) whereas ICC between 3DE and TDM was 0.75 (95% CI, 0.51-0.88). CONCLUSIONS: This study elucidated that LVSV is better estimated by 3DE-method compared to the conventional 2DE-method. This investigation will provide a more accurate, quick and noninvasive way of LVSV and cardiac output assessment at bedside by further application of 3DE. PMID- 22672367 TI - Skin graft vascular maturation and remodeling: a multifractal approach to morphological quantification. AB - OBJECTIVE: One important contributor to tissue graft viability is angiogenic maturation of the graft tissue bed. This study uses scale-invariant microvascular morphological quantification to track vessel maturation and remodeling in a split thickness skin-grafting model over 21 days, comparing the results to classical techniques. METHODS: Images from a previous study of split-thickness skin grafting in rats were analyzed. Microvascular morphology (fractal and multifractal dimensions, lacunarity, and vessel density) within fibrin interfaces of samples over time was quantified using classical semi-automated methods and automated multifractal and lacunarity analyses. RESULTS: Microvessel morphology increased in density and complexity, from three to seven days after engraftment and then regressed by 21 days. Vessel density increased from 0.07 on day 3 to 0.20 on day 7 and then decreased to 0.06 on day 21. A similar trend was seen for the fractal dimension that increased from 1.56 at three days to 1.77 at seven days then decreased to 1.57 by 21 days. Vessel diameters did not change whereas complexity and density did, signaling remodeling. CONCLUSIONS: This new automated analysis identified design parameters for tissue engraftment and could be used in other models of graft vessel biology to track proliferation and pruning of complex vessel beds. PMID- 22672368 TI - An alternative approach in fabrication of fixed complete dentures using a duplicate denture. AB - The traditional prosthetic steps in the fabrication of a fixed complete denture after implant osseointegration include final impression, verification of implant positioning in the working cast, mounting of the working cast, and mock denture wax trial insertion prior to the laboratory fabrication of the metal substructure; however, in patient scenarios of immediate loading of implants, the interim conversion prosthesis can be used to advance from the final impression to the milling of the underlying framework in one appointment. Consistency in the initial wax trial insertion, radiographic guide, and intraoral positioning of the conversion prosthesis can result in a well-designed definitive prosthesis in less time with the use of the existing duplicate complete denture. PMID- 22672369 TI - The road may be long, but you are on your way. PMID- 22672370 TI - The advocacy factor: the importance of grassroots movements in support of DWI policies. PMID- 22672371 TI - Developing countries ignore drinking and driving problems at their own peril. PMID- 22672372 TI - Achieving international progress on alcohol and traffic safety. PMID- 22672373 TI - Response to commentaries. PMID- 22672374 TI - Commentary on Jarl & Gerdtham (2012): further evidence of the reversal of alcohol related risk of oesophageal cancer after alcohol cessation. PMID- 22672375 TI - Commentary on Roerecke & Rehm (2012): The state of the science on moderate drinking and health--a case of heterogeneity in and heterogeneity out? PMID- 22672376 TI - Commentary on Elkashef et al. (2012): just enough efficacy for a second look. PMID- 22672377 TI - Commentary on Hyggen (2012): subtle perils of large general population surveys. PMID- 22672378 TI - Commentary on Bruneau et al. (2012): injection of prescription opioid pain relievers and infectious disease risk. PMID- 22672379 TI - Commentary on O'Connor et al. (2012): planning to effectively ban menthol cigarettes. PMID- 22672380 TI - Is deep brain stimulation for addiction an acceptable crime control measure? PMID- 22672382 TI - Association between the ABO blood group and the human intestinal microbiota composition. AB - BACKGROUND: The mucus layer covering the human intestinal epithelium forms a dynamic surface for host-microbial interactions. In addition to the environmental factors affecting the intestinal equilibrium, such as diet, it is well established that the microbiota composition is individually driven, but the host factors determining the composition have remained unresolved. RESULTS: In this study, we show that ABO blood group is involved in differences in relative proportion and overall profiles of intestinal microbiota. Specifically, the microbiota from the individuals harbouring the B antigen (secretor B and AB) differed from the non-B antigen groups and also showed higher diversity of the Eubacterium rectale-Clostridium coccoides (EREC) and Clostridium leptum (CLEPT) groups in comparison with other blood groups. CONCLUSIONS: Our novel finding indicates that the ABO blood group is one of the genetically determined host factors modulating the composition of the human intestinal microbiota, thus enabling new applications in the field of personalized nutrition and medicine. PMID- 22672383 TI - Physiological and biochemical responses of Quercus pubescens to air warming and drought on acidic and calcareous soils. AB - The drought- and thermo-tolerant Quercus pubescens, a tree species growing on both acidic and calcareous soils in the sub-Mediterranean region, was exposed to soil drought (-60% to -80% soil water content) and air warming (+1.2 degrees C daytime temperature), singly and in combination. The experiment was conducted on two natural forest soils with similar texture but different pH (acidic and calcareous soils). The physiological (photosynthesis) and biochemical (antioxidant system) responses of Q. pubescens were investigated. On acidic soil, Q. pubescens had a higher reactive oxygen species (ROS) content than on calcareous soil, confirming that this species is better adapted to the latter soil type. A down-regulation of ascorbate-glutathione cycle enzymes suggests that ROS were used as signalling molecules. Air warming stimulated stomatal opening, while soil drought induced stomatal closure in the late afternoon and reduced Rubisco carboxylation efficiency. Photosynthetic performance in the combined treatment was higher than under single drought stress and similar to control and air warming. Q. pubescens biochemical responses depended on soil pH. On acidic soil, Q. pubescens trees exposed to air warming used ROS as signalling molecules. On calcareous soil, these trees were able to balance both soil drought and air warming stress, avoiding ROS toxic effects by increasing antioxidant enzyme activitiy and maintaining a high enzymatic antioxidant defence. When combined, drought and air warming induced either more severe (higher oxidative pressure and impairment of the light-harvesting complex) or different responses (decline of the thermal energy dissipation capacity) relative to the single stressors. Overall, however, Q. pubescens preserved the functionality of the photosynthetic apparatus and controlled the antioxidant system response, thus confirming its drought and thermo-tolerance and therefore its potential to adapt to the ongoing climate change. PMID- 22672384 TI - Androgen function in the pathophysiology and treatment of male Huntington's disease patients. AB - Low concentrations of circulating testosterone have been associated with dementia manifesting with advancing age and in neurodegenerative conditions. Huntington's disease (HD) is a dominantly inherited neurodegenerative disease with an invariably fatal outcome. Severe motor symptoms, psychosis and dementia are symptomatic hallmarks of the progression of HD that result from the dysfunction and death of neocortical and basal ganglia neurones. Treatments are directed toward manifest symptoms, although they are largely ineffectual in slowing or preventing disease progression. Emerging data have identified hypothamic pathologies in HD that result in endocrine disturbances. Clinically defined primary or secondary hypogonadism elicit low circulating testosterone concentrations and have been linked to the development of Alzheimer's disease in men. Examining similar neuroendocrine dysfunction in HD including the nature of manifest hypogonadism in male patients could allow an elucidation of the complex pathophysiology of HD and provide an impetus for hitherto untested testosterone replacement therapy. PMID- 22672385 TI - Young people at risk for psychosis: case finding and sample characteristics of the Oulu Brain and Mind Study. AB - AIM: Set within the general population-based Northern Finland Birth Cohort 1986, the Oulu Brain and Mind Study aims to explore the causes and pathogenesis of psychotic illness by following young people at risk for psychosis due to having a first-degree relative with psychotic illness or due to having experienced psychotic-like symptoms themselves. We report the study methods and explore the relationship between these definitions of high risk for psychosis and operational criteria for a prodromal psychosis syndrome based on interview. METHODS: Prospectively collected data from earlier follow-ups of this cohort were combined with health register data to categorize subjects as those with familial risk (n = 272), symptomatic risk (n = 117), psychosis (n = 78), attention deficit hyperactivity disorder (ADHD) (n = 103) and a sample of controls (n = 193) drawn randomly from the remaining cohort. The Structured Interview for Prodromal Syndromes (SIPS) was applied to all, 295 participants together with questionnaires measuring psychosis vulnerability and schizotypal traits. RESULTS: There were 29 (10%) current prodromal cases. Criteria for the current prodromal syndrome were fulfilled by 12% of the familial risk group and 19% of the symptomatic risk group, compared with 5% of the ADHD group and 4% of controls. CONCLUSION: We successfully detected young people with a prodromal psychosis syndrome although relatively few subjects deemed to be at high risk met the full operational criteria according to the SIPS interview. Combining methods from familial, clinical and psychometric high-risk approaches provides a tractable method for studying risk of psychosis in the general population. PMID- 22672386 TI - Expression of proto-oncogene KIT is up-regulated in subset of human meningiomas. AB - BACKGROUND: KIT is a proto-oncogene involved in diverse neoplastic processes. Aberrant kinase activity of the KIT receptor has been targeted by tyrosine kinase inhibitor (TKI) therapy in different neoplasias. In all the earlier studies, KIT expression was reported to be absent in meningiomas. However, we observed KIT mRNA expression in some meningioma cases. This prompted us to undertake its detailed analyses in meningioma tissues resected during 2008-2009. METHODS: Tumor tissues and matched peripheral blood samples collected from meningioma patients were used for detailed molecular analyses. KIT expression was ascertained immunohistochemically and validated by immunoblotting. KIT and KITLG transcript levels were discerned by reverse transcription quantitative real-time PCR (RT qPCR). Similarly, KIT amplification and allele loss were assessed by quantitative real-time (qPCR) and validated by fluorescence in situ hybridization (FISH) on the neoplastic tissues. Possible alterations of the gene at the nucleotide level were analyzed by sequencing. RESULTS: Contrary to earlier reports, KIT expression, was detected immunohistochemically in 20.6% meningioma cases (n = 34). Receptor (KIT) and ligand (KITLG) transcripts monitored by RT-qPCR were found to co-express (p = 0.048) in most of the KIT immunopositive tumors. 1/7 KIT positive meningiomas showed allele loss corroborated by reduced FISH signal in the corresponding neoplastic tissue. Sequence analysis of KIT showed M541L substitution in exon 10, in one of the immunopositive cases. However, its biological consequence remains to be uncovered. CONCLUSIONS: This study clearly demonstrates KIT over-expression in the human meningiomas. The data suggest that up-regulated KIT transcription (p < 0.001), instead of gene amplification (p > 0.05), is a likely mechanism responsible for altered KIT expression. Thus, KIT is a potential candidate for detailed investigation in the context of meningioma pathogenesis. PMID- 22672387 TI - Increased high-level gentamicin resistance in invasive Enterococcus faecium is associated with aac(6')Ie-aph(2")Ia-encoding transferable megaplasmids hosted by major hospital-adapted lineages. AB - Gentamicin is important in synergistic bactericidal therapy with cell wall agents for severe enterococcal infections. During 2003-2008, a 10-fold increase in the prevalence of high-level gentamicin resistance (HLGR), to above 50%, in blood culture isolates of Enterococcus faecium, was reported by the Norwegian Surveillance System for Antimicrobial Resistance. A representative national collection of invasive E. faecium isolates (n = 99) from 2008 was examined by a multilevel approach. Genotyping revealed a polyclonal population dominated by major hospital-associated lineages (mainly ST203, ST17, ST18, ST202 and ST192). The presence of aac(6')-Ie-aph(2")-Ia, encoding the bi-functional aminoglycoside modifying enzyme, was found in 98% of HLGR isolates (56/57). Furthermore, a significantly higher prevalence of potential virulence genes, toxin-antitoxin loci as well as pRE25 and pRUM type replicons was demonstrated in isolates belonging to major hospital-associated lineages compared to other sequence types. Megaplasmids of pLG1 replicon type (200-330 kb) were present in 90% of the isolates. Co-hybridization analyses revealed genetic linkage of aac(6')-Ie aph(2")-Ia to this replicon type. Transfer of HLGR-encoding plasmids was restricted to E. faecium. In conclusion, the increased prevalence of HLGR in invasive E. faecium in Norway is associated with hospital-adapted genetic lineages carrying aac(6')-Ie-aph(2")-Ia-encoding transferable megaplasmids of the pLG1 replicon type. PMID- 22672388 TI - The recurrent pain and sexual sequelae of provoked vestibulodynia: a perpetuating cycle. AB - INTRODUCTION: Optimal management of provoked vestibulodynia (PVD), thought to be the most common form of chronic dyspareunia, is unclear. AIM: To integrate recent brain data on chronic pain circuitry with stress-induced neuroendocrine mechanisms in the skin and the stress burden (allostatic load) of women with PVD; to also clarify the typical chronicity and negative sexual sequelae associated with PVD; and then review modulation of pain circuitry by cognitive therapy and mindfulness practice and apply to PVD management. Methods. Review of scientific publications in the areas of sexual medicine, pain, brain imaging, gynecology, stress response, mindfulness, and cognitive behavioral therapy (CBT). MAIN OUTCOME MEASURES: (i) A model of PVD to reflect its etiology, typical chronicity, and the detrimental effects on sexual function; (ii) Interventions of sexual rehabilitation based on principles underlying changes associated with CBT and mindfulness practice. RESULTS: A model emerges which reflects how stress-induced changes of pain amplification (central sensitization), characteristic of chronic pain conditions, may impair sexual response in addition to sexual dysfunction that arises from conscious pain avoidance and/or fear-related inattention to sexual cues. Stress from low self-acceptance may be a major component of the allostatic load present in women with PVD, only to be exacerbated by the sexual dysfunction precipitated by the pain of intercourse. Mindfulness-based CBT appears promising to target both the pain and sexual suffering from PVD. CONCLUSION: New findings on brain activity associated with recurrent clinical pain, functional brain changes associated with CBT and mindfulness, plus new data on stress systems within the skin along with data on increased stress load in women with PVD, support the use of mindfulness-based CBT for the recurrent pain and sexual suffering from PVD. PMID- 22672389 TI - Using phonocardiography to investigate maternal cardiac reserve function in gestational hypertension and pre-eclampsia. AB - AIM: This study used phonocardiography to investigate maternal cardiac reserve function in gestational hypertension and pre-eclampsia. METHOD: Ninety-nine pregnant women with gestational hypertension (50 cases) and pre-eclampsia (49 cases) were included in the study; 99 normotensive pregnant women acted as controls. Using phonocardiography, cardiac reserve function parameters for all participants were recorded: heart rate, the ratio of the first heart sound magnitude to the second heart sound magnitude (S1/S2) and the ratio of the diastolic duration to the systolic duration (D/S). RESULTS: The average values for S1/S2 in the pre-eclampsia and gestational hypertension groups were 4.3+/-2.2 and 2.2+/-1.1 respectively. The average D/S of the pre-eclampsia and gestational hypertension groups were 1.1+/-0.3 and 1.4+/-0.3 respectively. Cases of postnatal adverse maternal outcomes were only observed in the pre-eclampsia group. A small proportion (2 out of 28) suffered cardiac-related complications, with one of these two patients dying from cardiac failure. Both these cases had notably poor cardiac reserve function (S1/S2>5.00 and D/S<1) before delivery. The index S1/S2 increases and the index D/S decreases with increasing severity of hypertension complicated pregnancies. CONCLUSIONS: Our findings indicate that cardiac reserve function declines with the increasing severity of hypertension during pregnancy. Phonocardiography is a useful, convenient and clinically worthwhile technique to monitor cardiac reserve function parameters of pregnant women with pre-eclampsia. PMID- 22672390 TI - Successful implementation of clinical practice guidelines for pressure risk management in a home nursing setting. AB - RATIONALE: This paper reports an initiative which promoted evidence-based practice in pressure risk assessment and management among home nursing clients in Melbourne, Australia. AIM AND OBJECTIVES: The aim of this study was to evaluate the introduction and uptake of the Australian Wound Management Association Guidelines for the Prediction and Prevention of Pressure Ulcers. METHOD: In 2007 a pilot study was conducted. Nurse perspectives (n=21) were obtained via survey and a client profile (n=218) was generated. Audit of the uptake and continued use of the pressure risk screening tool, during the pilot study and later once implemented as standard practice organizational wide, was conducted. RESULTS: Nurses at the pilot site successfully implemented the practice guidelines, pressure risk screening was adopted and supporting resources were well received. Most clients were at low risk of pressure ulcer development. The pilot site maintained and extended their pilot study success, ensuring more than 90% of clients were screened for pressure risk over the 18 months which followed. All other sites performed less well initially, however subsequently improved, meeting the pilot sites success after 18 months. Two years later, the organization continues to screen more than 90% of all clients for pressure risk. CONCLUSION: Implementation of clinical practice guidelines was successful in the pilot project and pressure risk screening became a well-adopted practice. Success continued following organizational wide implementation. Pilot study findings suggest it may be prudent to monitor the pressure ulcer risk status of low risk clients so as to prevent increasing risk and pressure ulcer development among this group. PMID- 22672391 TI - Colorectal surgery: rigour and logic when treating pelvic floor disorders. PMID- 22672392 TI - Tourniquet use in knee replacement surgery: what is the evidence? PMID- 22672393 TI - Comminuted radial head fractures: picking up the pieces. PMID- 22672394 TI - The descending perineum 'comes of age'. PMID- 22672395 TI - Two literary icons at 200 - New England Journal of Medicine (NEJM) and Charles Dickens. PMID- 22672397 TI - Dirofilaria-induced fibrosis: an unusual cause of pelviureteric obstruction. PMID- 22672398 TI - Giant hydronephrosis mimicking massive ascites. PMID- 22672399 TI - Isolated gall bladder rupture following blunt trauma. PMID- 22672400 TI - Abdominal cryptorchidism presenting with an acute abdomen. PMID- 22672401 TI - Re: Role of fine needle aspiration cytology in the preoperative investigation of branchial cysts. PMID- 22672402 TI - Cerebellar haematoma requiring surgical evacuation: long-term outcome. PMID- 22672403 TI - Modified pull-out suture in zone one injuries: button or gasket? PMID- 22672404 TI - Acute non-specific abdominal pain with port-wine urine. PMID- 22672405 TI - Interaction of Campylobacter spp. and human probiotics in chicken intestinal mucus. AB - Campylobacter is the most common cause of bacterial food-borne diarrhoeal disease throughout the world. The principal risk of human contamination is handling and consumption of contaminated poultry meat. To colonize poultry, Campylobacter adheres to and persists in the mucus layer that covers the intestinal epithelium. Inhibiting adhesion to the mucus could prevent colonization of the intestine. The aim of this study was to investigate in vitro the protective effect of defined commercial human probiotic strains on the adhesion of Campylobacter spp. to chicken intestinal mucus, in a search for alternatives to antibiotics to control this food-borne pathogen. The probiotic strains Lactobacillus rhamnosus GG and Propionibacterium freudenreichii ssp. shermanii JS and a starter culture strain Lactococcus lactis ssp. lactis adhered well to chicken intestinal mucus and were able to reduce the binding of Campylobacter spp. when the mucus was colonized with the probiotic strain before contacting the pathogen. Human-intended probiotics could be useful as prophylactics in poultry feeding for controlling Campylobacter spp. colonization. PMID- 22672406 TI - Transcatheter closure of persistent ductus arteriosus in adults. AB - OBJECTIVE: To describe the technical aspects and outcome of duct occlusion in adults over a 12-year period. METHODS: A single center review of all transcatheter duct closures performed between 2000 and 2012. RESULTS: Of 518 transcatheter duct closures performed, 31 patients were over the age of 16 at the time of procedure (6%). In 10 of the 31 cases, it was not possible to cross the duct from the pulmonary artery. In 4 of those, the duct was small enough to be closed with coils delivered from the aorta (although 1 required a second procedure for a residual shunt). In the remaining 6 cases, it was necessary to cross the duct from the aorta and create an arterio-venous "circuit" using a snare to deliver an Amplatzer device from the femoral vein. In none of the 487 children who underwent transcatheter duct closure during the same time period was it necessary to deliver the device using an arterio-venous wire circuit. The increased complexity of the procedure in adults compared with children was further reflected by longer procedure times (median of 37 minutes in adults vs. 24 minutes in children [P < 0.01]) and longer fluoroscopy times (median of 8.4 minutes in adults vs. 4.3 minutes in children [P < 0.025]). There were no major complications. CONCLUSIONS: Closure of the arterial duct in adults is safe and effective but ductal anatomy may differ from that seen in childhood, making transcatheter closure technically much more demanding than in children. PMID- 22672407 TI - A pilot randomised controlled trial of personalised care for depressed patients with symptomatic coronary heart disease in South London general practices: the UPBEAT-UK RCT protocol and recruitment. AB - BACKGROUND: Community studies reveal people with coronary heart disease (CHD) are twice as likely to be depressed as the general population and that this co morbidity negatively affects the course and outcome of both conditions. There is evidence for the efficacy of collaborative care and case management for depression treatment, and whilst NICE guidelines recommend these approaches only where depression has not responded to psychological, pharmacological, or combined treatments, these care approaches may be particularly relevant to the needs of people with CHD and depression in the earlier stages of stepped care in primary care settings. METHODS: This pilot randomised controlled trial will evaluate whether a simple intervention involving a personalised care plan, elements of case management and regular telephone review is a feasible and acceptable intervention that leads to better mental and physical health outcomes for these patients. The comparator group will be usual general practitioner (GP) care.81 participants have been recruited from CHD registers of 15 South London general practices. Eligible participants have probable major depression identified by a score of >=8 on the Hospital Anxiety and Depression Scale depression subscale (HADS-D) together with symptomatic CHD identified using the Modified Rose Angina Questionnaire. Consenting participants are randomly allocated to usual care or the personalised care intervention which involves a comprehensive assessment of each participant's physical and mental health needs which are documented in a care plan, followed by regular telephone reviews by the case manager over a 6 month period. At each review, the intervention participant's mood, function and identified problems are reviewed and the case manager uses evidence based behaviour change techniques to facilitate achievement of goals specified by the patient with the aim of increasing the patient's self efficacy to solve their problems.Depressive symptoms measured by HADS score will be collected at baseline and 1, 6- and 12 months post randomisation. Other outcomes include CHD symptoms, quality of life, wellbeing and health service utilisation. DISCUSSION: This practical and patient-focused intervention is potentially an effective and accessible approach to the health and social care needs of people with depression and CHD in primary care. TRIAL REGISTRATION: ISRCTN21615909. PMID- 22672409 TI - Prognostic value of echocardiographic-derived calcium index in coronary artery disease diagnosed by 64-multidetector computed tomography. AB - PURPOSE: To determine whether echocardiographic calcium index (ECI) calculated using transthoracic echocardiography (TTE) predicts coronary ischemic events. We also wished to determine coronary artery calcium score (CACS), the presence of obstructive coronary artery disease (CAD) and plaque composition, all of which were assessed by multidetector computed tomography (MDCT). METHODS: We carried out a prospective cohort study of 82 consecutive outpatients with chest pain and low-moderate risk of CAD, referred for noninvasive coronariography by MDCT. ECI was blindly assessed by TTE and correlated with subsequent cardiovascular events during a follow up period of 36 months. RESULTS: ECI values of >=7 had a sensitivity of 77.3%, a specificity of 90%, positive predictive value of 73.9%, and negative predictive value of 91.5% with respect to future coronary ischemic events. In addition, patients with ECI >= 7 showed a greater presence of severe calcified and obstructive CAD and a linear increase of obstructed vessels and mixed and calcified plaques, with a linear trend according to ECI values. CONCLUSION: ECI values of >=7 determine poor CAD prognosis in relation to ischemic events. Furthermore, ECI >= 7 may serve as a marker of content of coronary artery calcium, intraluminal obstruction, and plaque composition. Therefore, ECI seems to provide prognostic information as well as information about the characteristics of the plaque of atheroma. PMID- 22672410 TI - Relationship between esophageal contraction patterns and clearance of swallowed liquid and solid boluses in healthy controls and patients with dysphagia. AB - BACKGROUND: Non-obstructive dysphagia patients prove to be a difficult category for clinical management. Esophageal high-resolution manometry (HRM) is a novel method, used to analyze dysphagia. However, it is not yet clear how findings on HRM relate to bolus transport through the esophagus. METHODS: Twenty healthy volunteers and 20 patients with dysphagia underwent HRM and videofluoroscopy in a supine position. Each subject swallowed five liquid and five solid barium boluses. Esophageal contraction parameters and bolus transport were evaluated with HRM and concurrent videofluoroscopy. KEY RESULTS: Stasis of liquid and solid barium boluses occurred in patients and in healthy volunteers in 64% and 41% and in 84% and 82% of the swallows, respectively. Overall, 70% of the liquid and 72% of the solid bolus swallows were followed by a peristaltic contraction, the difference not being statistically significant. Statistically significant associations were found for transition zone length of liquid and solid boluses, and for DCI and distal contraction amplitudes for liquid stasis. No correlation was found between the degree of stasis and other manometric parameters. CONCLUSIONS & INFERENCES: Stasis of both liquid and solid boluses occurs frequently in patients and in controls and can be regarded as physiological. Motility patterns can predict the effectiveness of bolus transit and level of stasis to some degree but the relationship between esophageal motility and transit is complex and far from perfect. Esophageal manometry is therefore currently deemed unfit to be used for the prediction of bolus transit, and should rather be used for the identification of treatable esophageal motility disorders. PMID- 22672411 TI - A clinical evaluation of the I-gel TM supraglottic airway device in children. AB - BACKGROUND: The i-gel(TM) is one of the latest commercially available, second generation supraglottic airway devices (SADs). Specific features include a distal cuff made of a thermoplastic elastomer gel that does not require inflation and a gastric side channel to allow passage of a gastric tube, venting of gas from the stomach, and an early indication of regurgitation. Previous studies in older children and adults have shown that it is a reliable, efficient, and safe device for airway management. METHODS: We evaluated the i-gel(TM) in sizes ranging from 1 to 2.5 in children considered suitable for a supraglottic device. We assessed successful rates of insertion, airway leak pressure, position confirmed by fiberoptic laryngoscopy, gastric tube placement, manipulations required, and complications. RESULTS: The i-gel(TM) was used in 154 children over a period of 12 months. The median age [interquartile range (IQR)] was 4 years 11 months (2-7 years), median weight (IQR) 19 kg (13-26), and median (IQR) duration of procedure 29 (30-45) min. First insertion attempt was successful in 93.5% of patients, and second attempt in 5.8%. The median (IQR) time to insertion was 14 (13-16) s. The median (IQR) leak pressure was 20 (15-25) cmH(2) 0. Gastric tube placement was successful in 90% of cases. On fiberoptic examination, the vocal cords were visible in 97% of patients. Complications arose in 20% of patients, but the majority were minor. Anesthetists commented that the device had a tendency to displace upward out of the mouth and that extension toward the forehead and flexion toward the feet of the proximal tube altered the quality of the airway. Overall, in seven (4.5%) patients, the device was abandoned and an alternative airway was used. CONCLUSIONS: Pediatric i-gel(TM) sizes 1.5-2.5 provided a satisfactory airway during anesthesia for spontaneously breathing infants and children. However, to ensure a clear airway, considerable vigilance is required when fixing the device in the mouth and to avoid the negative effects of flexion of the proximal tubing. The i-gel(TM) is more expensive than first-generation devices. Whether this additional cost for the potential benefit of greater airway protection is considered acceptable will depend on longer-time evaluation and surveillance to establish overall safety. PMID- 22672412 TI - Prevention of post-thrombotic syndrome: a case for new oral anticoagulant drugs or for heparins? PMID- 22672414 TI - Arriba-lib: evaluation of an electronic library of decision aids in primary care physicians. AB - BACKGROUND: The successful implementation of decision aids in clinical practice initially depends on how clinicians perceive them. Relatively little is known about the acceptance of decision aids by physicians and factors influencing the implementation of decision aids from their point of view. Our electronic library of decision aids (arriba-lib) is to be used within the encounter and has a modular structure containing evidence-based decision aids for the following topics: cardiovascular prevention, atrial fibrillation, coronary heart disease, oral antidiabetics, conventional and intensified insulin therapy, and unipolar depression. The aim of our study was to evaluate the acceptance of arriba-lib in primary care physicians. METHODS: We conducted an evaluation study in which 29 primary care physicians included 192 patients. The physician questionnaire contained information on which module was used, how extensive steps of the shared decision making process were discussed, who made the decision, and a subjective appraisal of consultation length. We used generalised estimation equations to measure associations within patient variables and traditional crosstab analyses. RESULTS: Only a minority of consultations (8.9%) was considered to be unacceptably extended. In 90.6% of consultations, physicians said that a decision could be made. A shared decision was perceived by physicians in 57.1% of consultations. Physicians said that a decision was more likely to be made when therapeutic options were discussed "detailed". Prior experience with decision aids was not a critical variable for implementation within our sample of primary care physicians. CONCLUSIONS: Our study showed that it might be feasible to apply our electronic library of decision aids (arriba-lib) in the primary care context. Evidence-based decision aids offer support for physicians in the management of medical information. Future studies should monitor the long-term adoption of arriba-lib in primary care physicians. PMID- 22672413 TI - Unbalance of intestinal microbiota in atopic children. AB - BACKGROUND: Playing a strategic role in the host immune function, the intestinal microbiota has been recently hypothesized to be involved in the etiology of atopy. In order to investigate the gastrointestinal microbial ecology of atopic disease, here we performed a pilot comparative molecular analysis of the faecal microbiota in atopic children and healthy controls. RESULTS: Nineteen atopic children and 12 healthy controls aged 4-14 years were enrolled. Stools were collected and the faecal microbiota was characterized by means of the already developed phylogenetic microarray platform, HTF-Microbi.Array, and quantitative PCR. The intestinal microbiota of atopic children showed a significant depletion in members of the Clostridium cluster IV, Faecalibacterium prausnitzii, Akkermansia muciniphila and a corresponding increase of the relative abundance of Enterobacteriaceae. CONCLUSION: Depleted in key immunomodulatory symbionts, the atopy-associated microbiota can represent an inflammogenic microbial consortium which can contribute to the severity of the disease. Our data open the way to the therapeutic manipulation of the intestinal microbiota in the treatment of atopy by means of pharmaceutical probiotics. PMID- 22672416 TI - Quality of life assessments in advanced breast cancer: should there be more consistency? AB - Quality of life (QOL) measures have assumed increasing importance in assessing the impact of therapeutic drugs and interventions on patients and in making judgements about their cost-effectiveness. Important treatment decisions and crucial funding strategies involve QOL data and, for patients with a disease such as advanced breast cancer that impinges on their life expectancy, QOL can become a hugely important consideration. Yet, despite this, there is a lack of consensus on what defines an appropriate QOL measure, and inconsistency in the instruments that are chosen to measure it. The National Institute for Health and Clinical Excellence (NICE) is seen as a model for appraising the value of new treatments and NICE approval is required for treatments to be funded in the UK. In order to compare different disease conditions they use a generic measure, preferring the EQ-5D. We have performed a literature search of clinical trials in advanced breast cancer to establish which QOL measures have been used. Our findings show marked heterogeneity in terms of which QOL tools are used. It is suggested that there should be more consensus on which QOL instruments are used, not only between researchers, but between them and the bodies that approve funding. PMID- 22672415 TI - MET gain in diffuse astrocytomas is associated with poorer outcome. AB - Glioblastoma may develop rapidly without evidence for precursor lesions (primary glioblastomas), or progress from diffuse or anaplastic astrocytomas (secondary glioblastomas). Despite having distinct genetic profiles, these glioblastoma subtypes have similar histological features. We hypothesized that the highly malignant phenotype of glioblastoma may be attributable to genetic alterations that are common to both glioblastoma subtypes. In the present study, we first searched for commonly (>35%) amplified genes in glioblastomas with IDH1 mutation (a hallmark of secondary glioblastoma) and those without IDH1 mutation (typical for primary glioblastoma) in data from The Cancer Genome Atlas (TCGA). A total of 25 genes were identified, of which 21 were located at 7q31-34. We then screened 264 gliomas (70 glioblastomas, 112 diffuse astrocytomas, 82 oligodendrogliomas) for gain of the MET at 7q31.2 with quantitative polymerase chain reaction (PCR). MET gain was detected in primary glioblastomas (47%) and secondary glioblastomas (44%), suggesting that this genetic alteration plays a role in the pathogenesis of both glioblastoma subtypes. MET gain was also common in diffuse astrocytomas (38%), but less frequent in oligodendrogliomas (16%). MET gain in diffuse astrocytomas was associated with shorter survival (median, 43.0 vs. 70.7 months; P = 0.004), suggesting that MET gain is a useful prognostic marker for diffuse astrocytomas. PMID- 22672417 TI - A comparative in vitro study of two denture cleaning techniques as an effective strategy for inhibiting Candida albicans biofilms on denture surfaces and reducing inflammation. AB - PURPOSE: Candida albicans is the predominant oral yeast associated with denture induced stomatitis, and with an increasing population of denture wearers its incidence is increasing. Maintaining good oral and denture hygiene, through chemical and/or mechanical intervention, is essential to reducing this disease. The aim of this study, using a robust adherent C. albicans cell model system, was to evaluate and compare the efficacy of a novel denture cleanser to the efficacy of a commonly used dentifrice coupled with brushing. MATERIALS AND METHODS: Four C. albicans strains isolated from individuals diagnosed as having denture-induced stomatitis, were adhered to denture acrylic resin sections (1 cm(2) by 1 mm thickness) and after 4 hours of growth, challenged daily sequentially for 4 days with a denture cleanser (Polident) or intermittently with denture cleanser (day 1), then dentifrice (Colgate Cavity Protection Toothpaste) and brushing (days 2 and 3) and denture cleanser (day 4). Colony forming units were evaluated for each treatment, as were the levels of regrowth. Scanning electron microscopy (SEM) was also performed. Microbial susceptibility testing and time-kill studies were performed on biofilms. A coculture model was also used to assess interleukin-8 (IL-8) production from treated biofilms. RESULTS: It was shown that sequential treatment with the denture cleanser killed and inhibited regrowth each day. Intermittent treatment showed that viable C. albicans biofilms were only retained rather than being dispersed, which could be visualized by SEM. Time-kill studies demonstrated that the novel denture cleanser was highly active and killed quickly, unlike the dentifrice. IL-8 was expressed in greater levels in 24-hour biofilms than in 4-hour biofilms, but treatment with denture cleanser reduced IL 8 output. CONCLUSIONS: The data indicate that maintaining good oral health for denture wearers requires daily use of a denture cleanser rather than an alternating regimen. The inability of the denture cleanser to sterilize during intermittent treatments demonstrates the difficulty in controlling established biofilm. Moreover, the presence of mature biofilm may result in high levels of inflammation, but this can be controlled through denture cleansing. PMID- 22672419 TI - Treating scars: addressing surface, volume, and movement to expedite optimal results. Part 2: more-severe grades of scarring. AB - BACKGROUND: The management of scarring (after acne, surgery, or disease) is an ongoing challenge. METHODS: This is the second of two reviews and will use a grading scale of disease burden to classify scarred patients. Treatment discussion will concentrate on procedures exerting effect on volume and surface changes and the effects of movement. RESULTS: Treatment relevant to the type and severity of scarring will be discussed and tabulated treatment plans outlined. CONCLUSION: Severe grades of scarring often require a combination of filling agents for volume deficit, injectable agents for hypertrophic disease, neurotoxins to effect movement, and fractionated and ablative resurfacing for surface changes. PMID- 22672418 TI - Sildenafil promotes neuroprotection of the pelvic ganglia neurones after bilateral cavernosal nerve resection in the rat. AB - OBJECTIVE: To determine the gene expression profile of pelvic ganglia neurones after bilateral cavernosal nerve resection (BCNR) and subsequent treatment with sildenafil in relation to neurotrophic-related pathways. MATERIALS AND METHODS: Fisher rats aged 5 months were subjected to BCNR or sham operation and treated with or without sildenafil (20 mg/kg body-weight in drinking water) for 7 days. Total RNA isolated from pelvic ganglia was subjected to reverse transcription and then to quantitative reverse transcriptase-polymerase chain reaction (PCR) with the RAT-neurotrophic array. Results were corroborated by real-time PCR and western blotting. Another set of animals were injected with a fluorescent tracer at the base of the penis, 7 days before BCNR or sham operation, and were sacrificed 7 days after surgery. Sections of pelvic ganglia were used for immunohistochemistry with antibodies against neurturin, neuronal nitric oxide synthase, tyrosine hydroxylase and glial cell line-derived neurotrophic factor receptor alpha2. RESULTS: A down-regulation of the expression of neuronal nitric oxide synthase accompanied by changes in the level of cholinergic neurotrophic factors, such as neurturin and its receptor glial cell line-derived neurotrophic factor receptor alpha2, artemin, neurotrophin-4 and cilliary neurotrophic factor, was observed 7 days after BCNR in pelvic ganglia neurones. Treatment with sildenafil, starting immediately after surgery, reversed all these changes at a level similar to that in sham-operated animals. CONCLUSIONS: Sildenafil treatment promotes changes in the neurotrophic phenotype, leading to a regenerative state of pelvic ganglia neurones. The present study provides a justification for the use of phosphodiesterase 5 inhibitors as a neuroprotective agent after BCNR. PMID- 22672420 TI - The influences of skin visco-elasticity, hydration level and aging on the formation of wrinkles: a comprehensive and objective approach. AB - BACKGROUND: Various skin parameters including skin visco-elasticity and hydration level affect the formation of wrinkles. OBJECTIVE: The aim of this study was to investigate the comprehensive and objective relationship between age, skin visco elasticity, hydration level, and the occurrence of wrinkles using bioengineering equipments for the first time. METHODS: A total number of 97 healthy women were included in this study. Age, Fitzpatrick skin type, skin mechanical parameters obtained with Cutometer(R0~R9), hydration level measured with Corneometer, as well as wrinkle parameters (SEsm, SEr, SEsc, and SEw) assessed with Visioscan, were analyzed with the Pearson's correlation test. RESULTS: The skin fluidity (R6) increased while the elastic recovery ratio (R7) decreased with the age. The wrinkle parameter (SEw) also increased with the age. The higher skin hysteresis values (R4 and R9) coincided with the higher SEw values. Skin hydration significantly lowered the hysteresis (R9), the wrinkles (SEw), and the depth of wrinkle furrows (R3mr). CONCLUSION: The elderly have less elastic skin and more wrinkles. Skin hysteresis most closely related with the degree of wrinkles. Drier skin showed more wrinkles and deeper furrows, with wider intervals. On the basis of these objective findings, we propose several skin parameters associated with wrinkles, and hypothesize the mechanism of wrinkle generation. PMID- 22672421 TI - Critical phases in the seed development of common juniper (Juniperus communis). AB - Common juniper (Juniperus communis L.) populations in northwest European lowlands are currently declining in size and number. An important cause of this decline is a lack of natural regeneration. Low seed viability seems to be one of the main bottlenecks in this process. Previous research revealed a negative relation between seed viability and both temperature and nitrogen deposition. Additionally, the seeds of common juniper have a variable ripening time, which possibly influences seed viability. However, the underlying mechanisms remain unresolved. In order to elucidate this puzzle, it is important to understand in which phases of seed production the main defects are situated, together with the influence of ripening time. In this study, we compared seed viability of populations with and without successful recruitment. We examined three seed phases: (i) gamete development; (ii) fertilisation and early-embryo development; and (iii) late-embryo development. After the first two phases, we found no difference in the percentage viable seeds between populations with or without recruitment. After late-embryo development, populations without recruitment showed a significantly lower percentage of viable seeds. These results suggest that late-embryo development is a bottleneck in seed development. However, the complex interaction between seed viability and ripening time suggest that the causes should be in the second seed phase, as the accelerated development of male and female gametophytes may disturb the male-female synchrony for successful mating. PMID- 22672422 TI - Dynamic flux balance analysis of the metabolism of Saccharomyces cerevisiae during the shift from fully respirative or respirofermentative metabolic states to anaerobiosis. AB - Dynamic flux balance analysis was utilized to simulate the metabolic behaviour of initially fully respirative and respirofermentative steady-state cultures of Saccharomyces cerevisiae during sudden oxygen depletion. The hybrid model for the dynamic flux balance analysis included a stoichiometric genome-scale metabolic model as a static part and dynamic equations for the uptake of glucose and the cessation of respirative metabolism. The yeast consensus genome-scale metabolic model [Herrgard MJ et al. (2008) Nat Biotechnol 26, 1155-1160; Dobson PD et al. (2010) BMC Syst Biol 4, 145] was refined with respect to oxygen-dependent energy metabolism and further modified to reflect S. cerevisiae anabolism in the absence of oxygen. Dynamic flux balance analysis captured well the essential features of the dynamic metabolic behaviour of S. cerevisiae during adaptation to anaerobiosis. Modelling and simulation enabled the identification of short time scale flux distribution dynamics under the transition to anaerobic metabolism, during which the specific growth rate was reduced, as well as longer time-scale process dynamics when the specific growth rate recovered. Expression of the metabolic genes was set into the context of the identified dynamics. Metabolic gene expression responses associated with the specific growth rate and with the cessation of respirative metabolism were distinguished. PMID- 22672423 TI - Exploring young people's expectations of a youth mental health care service. AB - Client expectations about mental health services relate to the client's and the therapist's role, the therapeutic process and therapeutic outcomes. Research with adults shows that such expectations affect service engagement and clinical outcomes. AIM: The present study investigated expectations for adolescents and young adults, which have not been adequately investigated and may partly explain the reluctance of young people to seek professional help. METHODS: Participants included 20 young people aged 12-24 attending their initial session at a youth mental health service, who were interviewed immediately prior to their initial session. Data were analysed using qualitative methods to draw main themes around each of the four expectancy types. RESULTS: Overall, the strongest theme was that young people were unsure of what to expect from attending a mental health service. The key theme for expectations of their role as a client was readiness for therapy, and for the therapist's role the key themes were who they expected to see, the directiveness and likeability of the therapist, and the type of help they expected they would receive. The young people expected that the therapy process would involve simply talking and expected their engagement to be dependent on how much they liked their first few sessions. Outcome expectations were non-specific and the theme of hopefulness was most evident. CONCLUSION: As unrealistic and unmet expectations can lead to poorer engagement and outcomes in therapy, the study highlights a need for young people to be better informed about what to expect when coming to mental health services. PMID- 22672424 TI - GDNF contributes to oestrogen-mediated protection of midbrain dopaminergic neurones. AB - Parkinson's disease (PD) is characterised by the preferential loss of dopaminergic neurones from the substantia nigra (SN) that leads to the hallmark motor disturbances. Animal and human studies suggest a beneficial effect of oestrogen to the nigrostriatal system, and the regulation of neurotrophic factor expression by oestrogens has been suggested as a possible mechanism contributing to that neuroprotective effect. The present study was designed to investigate whether the neuroprotection exerted by 17beta-oestradiol on nigrostriatal dopaminergic neurones is mediated through the regulation of glial cell line derived neurotrophic factor (GDNF) expression. Using an in vivo rat model of PD, we were able to confirm the relevance of 17beta-oestradiol in defending dopaminergic neurones against 6-hydroxydopamine (6-OHDA) toxicity. 17beta oestradiol, released by micro-osmotic pumps, implanted 10 days before intrastriatal 6-OHDA injection, prevented the loss of dopaminergic neurones induced by 6-OHDA. 17beta-oestradiol treatment also promoted an increase in GDNF protein levels both in the SN and striatum. To explore the relevance of GDNF increases to 17beta-oestradiol neuroprotection, we analysed, in SN neurone-glia cultures, the effect of GDNF antibody neutralisation and RNA interference mediated GDNF knockdown. The results showed that both GDNF neutralisation and GDNF silencing abolished the dopaminergic protection provided by 17beta oestradiol against 6-OHDA toxicity. Taken together, these results strongly identify GDNF as an important player in 17beta-oestradiol-mediated dopaminergic neuroprotection. PMID- 22672425 TI - Roles of microRNA-34a in the pathogenesis of placenta accreta. AB - AIM: MicroRNA-34a (miR-34a) is associated with invasion and metastasis of various cancers. The trophoblastic cells of placenta accreta invade into the myometrium in a similar way to the invasion of cancers. We studied the roles of miR-34a in the pathogenesis of placenta accreta. METHODS: The human choriocarcinoma cell line JAR was used for in vitro experiments as a model of trophoblasts, and placental tissues from the operative specimen of patients with or without placenta accreta were used for experiments in vivo. Morpholino antisense oligomer against miR-34a (miR-34a Morpho/AS) was added to JAR, and the expression of miR 34a and plasminogen activator inhibitor-1 (PAI-1) was determined by real time PCR. The effects of antisense, interleukin (IL)-6 and IL-8 in the process of invasion were studied with an invasion assay. Expression of miR-34a in vivo was studied with the use of fluorescent in situ hybridization (FISH). RESULTS: Expression of miR-34a was inhibited by 65% with the administration of antisense, and a slight increase in miR-34a expression was observed with the addition of IL 6 and IL-8. PAI-1 expression decreased with the addition of IL-6 and IL-8, and increased with the administration of antisense. There was an increase in invasive capacity through the inhibition of miR-34a expression. Strong FISH expression of miR-34a was observed in trophoblast cells of non-placenta accreta, and a clear decrease in miR-34a expression was observed in those of placenta accreta. CONCLUSIONS: Expression of miR-34a was downregulated in placenta accreta. In vitro experiments also showed that the invasive potential of JAR increased by suppressing miR-34a, probably through the expression of PAI-1. PMID- 22672426 TI - Identification of key proteins of cultured human intestinal cells involved in interaction with enteroaggregative Escherichia coli. AB - Enteroaggregative Escherichia coli (EAEC) adherence to human intestinal tissue is known to be mediated by aggregative adherence fimbriae (AAF). However, the host cell molecules involved in EAEC adherence remain uncharacterized. In the present study, four key membrane glycoproteins of cultured human intestinal epithelial cells (INT-407) were found to be involved in the interaction with the T8 strain of EAEC. Nine membrane proteins of INT-407 cells were found to interact with EAEC T8, of which four were identified as fibronectin, epidermal growth factor receptor (EGFR), Thrombospondin-1 (TSP1) and glucose-regulated protein (GRP-94). Our findings were validated by Western blot using antibody against each identified protein. The adherence of EAEC-T8 to INT-407 cells was reduced to c. 26, 29, 37 and 76% in the presence of the antibody against GRP-94, EGFR, fibronectin and TSP-1, respectively. These findings were further substantiated by flow cytometry, where the final mean fluorescence intensity value of the INT-407 cells (c. 1075) resulting from adherent-labelled bacteria was found to be reduced to c. 26, 132, 228 and 597 in the presence of antibody against GRP-94, EGFR, fibronectin and TSP-1. We propose that GRP-94, EGFR, fibronectin and TSP-1 are involved in the aggregative adherence of EAEC-T8 to INT-407 cells. PMID- 22672428 TI - Exploring women's postpartum sexuality: social, psychological, relational, and birth-related contextual factors. AB - INTRODUCTION: Women's postpartum sexuality can be influenced by factors related to physical, personal, and relationship transitions after the newborn arrives. Despite this, many experiential and social factors remain unexplored. AIMS: This study aims to (i) investigate a range of variables thought to influence postpartum sexuality; (ii) expand the focus beyond latency to penis-vagina intercourse; and (iii) assess positive aspects of postpartum sexuality. METHODS: Via retrospective reporting on the first 3 months postpartum, 304 women completed an online questionnaire. MAIN OUTCOME MEASURES: The main outcome measures were retrospective reports of sexual desire (Sexual Desire Inventory), latency to resumption of sexual activity, and perceptions of partner's sexual desire. Other measures were birth experience (Questionnaire Measuring Attitudes About Labor and Delivery), breastfeeding status, perceptions of social support (Multidimensional Scale of Perceived Social Support), stress (Perceived Stress Scale), and body image (Body Image Self-Consciousness Scale). RESULTS: Significant differences in time to resumption were found. Women performed oral sex on their partners earlier than engaging in masturbation, which was followed by intercourse and then receiving oral sex. Post hoc analyses identified birth experience, social support, importance of partner's sexual fulfillment, and perception of partner's desire as contributors to this pattern. Women's postpartum sexual desire was influenced by their perceptions of their partner's postpartum sexuality and individual's level of fatigue. Results suggested that postpartum desire was not significantly influenced by breastfeeding status, vaginal issues, or psychosocial variables including stress, body image, or social support. CONCLUSION: Results suggest that women's perceptions of their partner's sexuality impact postpartum sexuality more than the physical factors most commonly studied (e.g., vaginal trauma and breastfeeding). These results portray postpartum sexuality as a multidimensional phenomenon and highlight the need for further research that addresses its social context. PMID- 22672427 TI - Concurrent epigenetic silencing of wnt/beta-catenin pathway inhibitor genes in B cell chronic lymphocytic leukaemia. AB - BACKGROUND: The Wnt/beta-catenin signalling is aberrantly activated in primary B cell chronic lymphocytic leukaemia (CLL). Epigenetic silencing of pathway inhibitor genes may be a mechanism for its activation. In this study, we investigated systematically and quantitatively the methylation status of 12 Wnt/beta-catenin pathway inhibitor genes - CDH1, DACT1, DKK1, DKK2, DKK3, DKK4, SFRP1, SFRP2, SFRP3, SFRP4, SFRP5 and WIF1 - in the cell lines EHEB and MEC-1 as well as patient samples. METHODS: Quantification of DNA methylation was performed by means of bisulphite pyrosequencing and confirmed by bisulphite Sanger sequencing. Gene expression was analysed by qPCR using GAPDH as internal control. E-cadherin and beta-catenin protein quantification was carried out by microsphere based immunoassays. Methylation differences observed between the patient and control groups were tested using generalised least squares models. RESULTS: For 10 genes, a higher methylation level was observed in tumour material. Only DKK4 exhibited similarly high methylation levels in both tumour and normal specimens, while DACT1 was always essentially unmethylated. However, also for these inhibitors, treatment of cells with the demethylating agent 5-aza-2' deoxycytidine resulted in an induction of their expression, as shown by quantitative PCR, suggesting an indirect epigenetic control of activity. While the degree of demethylation and its transcriptional consequences differed between the genes, there was an overall high correlation of demethylation and increased activity. Protein expression studies revealed that no constitutive Wnt/beta catenin signalling occurred in the cell lines, which is in discrepancy with results from primary CLL. However, treatment with 5-aza-2'-deoxycytidine caused accumulation of beta-catenin. Simultaneously, E-cadherin expression was strongly induced, leading to the formation of a complex with beta-catenin and thus demonstrating its epigenetically regulated inhibition effect. CONCLUSIONS: The results suggest an epigenetic silencing mechanism of the Wnt/beta-catenin pathway inhibitor genes in CLL. Hypermethylation and silencing of functionally related genes may not be completely stochastic but result from the tumour epigenome reprogramming orchestrated by Polycomb-group repressive complexes. The data are of interest in the context of epigenetic-based therapy. PMID- 22672429 TI - Information-searching behaviors of main and allied health professionals: a nationwide survey in Taiwan. AB - RATIONALE, AIMS AND OBJECTIVES: There are a variety of resources to obtain health information, but few studies have examined if main and allied health professionals prefer different methods. The current study was to investigate their information-searching behaviours. METHODS: A constructed questionnaire survey was conducted from January through April 2011 in nationwide regional hospitals of Taiwan. Questionnaires were mailed to main professionals (physicians and nurses) and allied professionals (pharmacists, physical therapists, technicians and others), with 6160 valid returns collected. RESULTS: Among all professional groups, the most commonly used resource for seeking health information was a Web portal, followed by colleague consultations and continuing education. Physicians more often accessed Internet-based professional resources (online databases, electronic journals and electronic books) than the other groups (P < 0.05). In contrast, physical therapists more often accessed printed resources (printed journals and textbooks) than the other specialists (P < 0.05). And nurses, physical therapists and technicians more often asked colleagues and used continuing education than the other groups (P < 0.01). The most commonly used online database was Micromedex for pharmacists and MEDLINE for physicians, technicians and physical therapists. Nurses more often accessed Chinese-language databases rather than English-language databases (P < 0.001). CONCLUSIONS: This national survey depicts the information-searching pattern of various health professionals. There were significant differences between and within main and allied health professionals in their information searching. The data provide clinical implications for strategies to promote the accessing of evidence-based information. PMID- 22672430 TI - An asymptomatic needle in the left ventricular anterolateral wall: a prison inmate's strange radio antenna. AB - A foreign body such as a needle in the heart can be life-threatening. While this may occur accidentally, needles may be inserted into the body by psychiatric patients or in cases involving domestic violence. A needle can migrate through the thorax toward the heart. In drug users, needles may also reach the right ventricle via the peripheral veins. Cardiac injury can occur via the esophagus after swallowing a needle. The clinical outcome may vary from an asymptomatic situation to tamponade or shock, depending on how severely the cardiac structures are affected. In injuries involving the thorax, pneumothorax may cause sudden shortness of breath. Here, we report the case of a 34-year-old male prison inmate who accidentally lodged a pin in his left ventricle while asleep. As he has refused surgery, it was decided to follow the patient carefully. PMID- 22672431 TI - Lack of association of non-synonymous FUT2 and ALPL polymorphisms with venous thrombosis. PMID- 22672432 TI - Assessing falls risk in older adult mental health patients: a Western Australian review. AB - Falls are a common and costly complication of hospitalization, particularly in older adult populations. This paper presents the results of a review of 139 falls at two older adult mental health services in Western Australia, Australia, over a 12-month period. Data were collected from the hospital incident report management system and from case file reviews of patients who sustained a fall during hospitalization. The results demonstrated that the use of different risk assessment and falls management tools led to variations in practice, policies, and management strategies. The review identified mental health-specific falls risk factors that place older people with a mental illness at risk when admitted to the acute mental health setting. With the expansion of community mental health care, many older people with a mental illness are now cared for in a variety of health-care settings. In assessing falls risk and implementing falls-prevention strategies, it is important for clinicians to recognize this group as an ambulant population with a fluctuating course of illness. They have related risks that require specialized falls assessment and management. PMID- 22672433 TI - Transradial Szabo technique for intervention of ostial lesions. AB - OBJECTIVES: The aim of our study is to assess the feasibility and safety of transradial intervention (TRI) of coronary ostial lesions using the Szabo technique. BACKGROUND: When performing TRI of coronary ostial lesions, precise stent positioning is of paramount importance. TRI has experienced increasing popularity in the U.S.; however, utilization of the Szabo technique has not been systematically evaluated in this setting. We report the results of ostial stent deployment using the Szabo technique for 2 experienced TRI operators and centers. METHODS: This was a retrospective analysis of 40 consecutive patients who underwent PCI from April 2009 to September 2011. All patients who underwent PCI via the transradial route with the Szabo technique for ostial lesions performed by experienced transradial operators (>200 cases/yr) were included. RESULTS: In our study of 40 patients with 41 coronary ostial lesions, overall procedural success rate was 100%. Stent dislodgement was seen in 1 patient. Clinical follow up was 100%, with a mean duration of 292.7+/-200 days. Target lesion revascularization (TLR) was seen in 2 patients (5%). One patient had an episode of transient ischemic attack (TIA) at 33 days after PCI; another experienced subacute stent thrombosis at 81 days while on dual antiplatelet therapy. MACE was 7.5% overall. CONCLUSION: In our study, treatment of coronary ostial lesions with the Szabo technique via TRI is associated with a high procedural success rate and a low MACE of 7.5%. PMID- 22672434 TI - Investigating incursions of bluetongue virus using a model of long-distance Culicoides biting midge dispersal. AB - Bluetongue virus (BTV) is an economically important pathogen of ruminants that is the aetiological agent of the haemorrhagic disease bluetongue. Bluetongue virus is biologically transmitted by Culicoides biting midges (Diptera: Ceratopogonidae), and long-range dispersal of infected vector species contributes substantially to the rapid spread of the virus. The range of semi-passive flights of infected Culicoides on prevailing winds has been inferred to reach several hundred kilometres in a single night over water bodies. In this study, an atmospheric dispersion model was parameterized to simulate Culicoides flight activity based on dedicated entomological data sets collected in the UK. Five outbreaks of BTV in Europe were used to evaluate the model for use as an early warning tool and for retrospective analyses of BTV incursions. In each case, the generated predictions were consistent with epidemiological observations confirming its reliability for use in disease outbreak management. Furthermore, the model aided policy makers to predict, contain and eradicate BTV outbreaks in the UK during 2007 and 2008. PMID- 22672435 TI - Glomerular disease search filters for Pubmed, Ovid Medline, and Embase: a development and validation study. AB - BACKGROUND: Tools to enhance physician searches of Medline and other bibliographic databases have potential to improve the application of new knowledge in patient care. This is particularly true for articles about glomerular disease, which are published across multiple disciplines and are often difficult to track down. Our objective was to develop and test search filters for PubMed, Ovid Medline, and Embase that allow physicians to search within a subset of the database to retrieve articles relevant to glomerular disease. METHODS: We used a diagnostic test assessment framework with development and validation phases. We read a total of 22,992 full text articles for relevance and assigned them to the development or validation set to define the reference standard. We then used combinations of search terms to develop 997,298 unique glomerular disease filters. Outcome measures for each filter included sensitivity, specificity, precision, and accuracy. We selected optimal sensitive and specific search filters for each database and applied them to the validation set to test performance. RESULTS: High performance filters achieved at least 93.8% sensitivity and specificity in the development set. Filters optimized for sensitivity reached at least 96.7% sensitivity and filters optimized for specificity reached at least 98.4% specificity. Performance of these filters was consistent in the validation set and similar among all three databases. CONCLUSIONS: PubMed, Ovid Medline, and Embase can be filtered for articles relevant to glomerular disease in a reliable manner. These filters can now be used to facilitate physician searching. PMID- 22672437 TI - Anesthesia for children with pericardial effusion: a case series. AB - OBJECTIVES AND AIMS: To review the anesthetic management of children requiring surgical intervention for pericardial effusion, determine the nature and frequency of complications and define risk factors that predict perioperative risk. BACKGROUND: Anesthesia in the presence of a pericardial effusion may be associated with significant hemodynamic compromise particularly during induction. However, the literature specifically concerning children is limited to a single case report. METHODS: A retrospective case review of children undergoing general anesthesia for surgical treatment for pericardial effusion between 1999 and 2008 at a single institution. RESULTS: Sixty-five children underwent 79 general anesthetics for surgical treatment for pericardial effusion. Median age was 4 years (2 weeks-16 years), and median weight 15 kg (range, 2.5-96 kg). Fifty-five children (84%) developed effusions following cardiac surgery. The commonest induction agent was ketamine (25/65, 38%), and the majority of children (52/65, 80%) were intubated and ventilated for the procedure. Seven children (11%) suffered from eight major complications, and 14 children (22%) suffered from a minor complication. Major complications were more common in children with preoperative tachypnoea (P = 0.01) and cardiac tamponade on preoperative echocardiogram (ECHO) (P = 0.001). Preoperative hypoxia had a sensitivity of 92% and a positive likelihood ratio of 5.2 (95% CI 1.5-17.5) for predicting all complications. CONCLUSIONS: Anesthesia for pericardial effusion in children was associated with an adverse physiological event in one-third of children. Major complications may be predicted by preoperative tachypnoea and cardiac tamponade on preoperative ECHO, and all complications may be predicted by preoperative hypoxia. The anesthetic technique included a variety of induction agents, and we cannot recommend a particular approach. PMID- 22672436 TI - Detection of mixed populations of wild-type and YMDD hepatitis B variants by pyrosequencing in acutely and chronically infected patients. AB - BACKGROUND: Lamivudine (LAM) is associated with the highest known rate of resistance mutations among nucleotide analogs used to treat chronic hepatitis B virus (HBV) infection. Despite this, LAM continues in widespread use, especially in combination therapies. The primary LAM resistance mutation (rtM204V/I) occurs in the YMDD motif of HBV polymerase. The aim of this study was to characterize Brazilian HBV isolates from acute and chronic cases by direct sequencing, and to identify HBV quasispecies in the YMDD motif using a pyrosequencing method capable of detecting single-nucleotide polymorphisms. HBV DNA from serum samples of 20 individuals with acute HBV infection and 44 with chronic infection undergoing antiviral therapies containing LAM were analyzed by direct sequencing and pyrosequencing methods. RESULTS: Phylogenic analyses of direct-sequenced isolates showed the expected genotypes (A, D and F) for the Brazilian population in both acute and chronic infections. However, within genotype A isolates, subgenotype A2 was more frequently detected in acute cases than in chronic cases (P = 0.012). As expected, none of the individuals with acute hepatitis B had LAM-resistant isolates as a dominant virus population, whether detected by direct sequencing or pyrosequencing. However, pyrosequencing analyses showed that 45% of isolates (9/20) had minor subpopulations (4-17%) of LAM-resistant isolates. Among chronic patients undergoing LAM treatment, YMDD mutants were frequently found as a dominant virus population. In cases where wild-type virus was the dominant population, subpopulations of YMDD variants were usually found, demonstrating the complexity of HBV quasispecies. CONCLUSIONS: YMDD variants were frequently detected as a minor population in acute HBV infection. The occurrence of pre existing variants may lead to a high frequency of resistant mutants during antiviral therapy in the chronic phase. In chronic infection, detection of YMDD variants before virological or biochemical breakthrough might contribute to making better therapy choices and thus improving treatment outcome. PMID- 22672438 TI - An information transmission model for transcription factor binding at regulatory DNA sites. AB - BACKGROUND: Computational identification of transcription factor binding sites (TFBSs) is a rapid, cost-efficient way to locate unknown regulatory elements. With increased potential for high-throughput genome sequencing, the availability of accurate computational methods for TFBS prediction has never been as important as it currently is. To date, identifying TFBSs with high sensitivity and specificity is still an open challenge, necessitating the development of novel models for predicting transcription factor-binding regulatory DNA elements. RESULTS: Based on the information theory, we propose a model for transcription factor binding of regulatory DNA sites. Our model incorporates position interdependencies in effective ways. The model computes the information transferred (TI) between the transcription factor and the TFBS during the binding process and uses TI as the criterion to determine whether the sequence motif is a possible TFBS. Based on this model, we developed a computational method to identify TFBSs. By theoretically proving and testing our model using both real and artificial data, we found that our model provides highly accurate predictive results. CONCLUSIONS: In this study, we present a novel model for transcription factor binding regulatory DNA sites. The model can provide an increased ability to detect TFBSs. PMID- 22672439 TI - Problem drinking and physical intimate partner violence against women: evidence from a national survey in Uganda. AB - BACKGROUND: Problem drinking has been identified as a major risk factor for physical intimate partner violence (PIPV) in many studies. However, few studies have been carried on the subject in developing countries and even fewer have a nationwide perspective. This paper assesses the patterns and levels of PIPV against women and its association with problem drinking of their sexual partners in a nationwide survey in Uganda. METHODS: The data came from the women's dataset in the Uganda Demographic and Health Survey of 2006. Problem drinking among sexual partners was defined by women's reports that their partner got drunk sometimes or often and served as the main independent variable while experience of PIPV by the women was the main dependent variable. In another aspect problem drinking was treated an ordinal variable with levels ranging from not drinking to getting drunk often. A woman was classified as experiencing PIPV if her partner pushed or shook her; threw something at her; slapped her; pushed her with a fist or a harmful object; kicked or dragged her, tried to strangle or burn her; threatened/attacked her with a knife/gun or other weapon. General chi-square and chi-square for trend analyses were used to assess the significance of the relationship between PIPV and problem drinking. Multivariate analysis was applied to establish the significance of the relationship of the two after controlling for key independent factors. RESULTS: Results show that 48% of the women had experienced PIPV while 49.5% reported that their partners got drunk at least sometimes. The prevalence of both PIPV and problem drinking significantly varied by age group, education level, wealth status, and region and to a less extent by occupation, type of residence, education level and occupation of the partner. Women whose partners got drunk often were 6 times more likely to report PIPV (95% CI: 4.6-8.3) compared to those whose partners never drank alcohol. The higher the education level of the women the less the likelihood of experiencing PIPV (ptrend < 0.001). Similar relationship was found between wealth status and experiencing PIPV. CONCLUSIONS: Problem drinking among male partners is a strong determinant of PIPV among women in Uganda. PIPV prevention measures should address reduction of problem drinking among men. Longerterm prevention measures should address empowerment of women including ensuring higher education, employment and increased income. PMID- 22672440 TI - Loss of INI1 protein expression defines a subgroup of aggressive central nervous system primitive neuroectodermal tumors. AB - Pediatric embryonal brain tumors can be difficult to classify. Atypical teratoid rhabdoid tumors (ATRT) contain rhabdoid cells, while primitive neuroectodermal tumors (PNETs) are composed of "small round blue cells." Loss of INI1 is a common event in ATRT; therefore, we investigated if the loss of INI1 protein expression was also observed in central nervous system (CNS) PNET and pineoblastoma. A histological review of 42 CNS PNETs and six pineoblastomas was performed. INI1 expression was assessed by immunohistochemistry. Sequencing was performed on the mutational hotspots of INI1. INI1-immunonegative tumors were further investigated using fluorescence in situ hybridization. Epithelial membrane antigen (EMA) protein expression was assessed in six CNS PNETs to further define the phenotype. Five CNS PNETs without rhabdoid cell morphology were immuno-negative for both INI1 and EMA. Of these primary CNS PNET patients, three died <11 months postdiagnosis, which was dissimilar to the INI1-immunopositive primary CNS PNETs where 18/24 (75%) patients were alive 1 year postdiagnosis. We have identified a small subgroup of CNS PNETs which lack INI1 protein expression, but have no evidence of rhabdoid cell morphology. INI1 protein loss may occur through mechanisms other than gene deletion. INI1 immunohistochemistry should be performed for all CNS PNET cases. PMID- 22672441 TI - Impact of eLearning course on nurses' professional competence in seclusion and restraint practices: 9-month follow-up results of a randomized controlled study (ISRCTN32869544). AB - eLearning may facilitate continuing vocational education, but data on the long term effects of an eLearning course are lacking. The aim of this study was to explore the long-term impact of an eLearning course entitled ePsychNurse.Net on psychiatric nurses' professional competence in practicing seclusion and restraint and on their job satisfaction and general self-efficacy at 9-month follow-up. In a randomized controlled study, 12 wards were randomly assigned to the ePsychNurse.Net (intervention) or training as usual (control). Baseline and 9 month follow-up data on nurses' knowledge of coercion-related legislation, physical restraint and seclusion, their attitudes towards physical restraint and seclusion, job satisfaction and general self-efficacy were analysed for 137 completers (those who participated in the 9-month follow-up assessment). No between-group differences were found on any variable, with the exception of a change in attitude to seclusion in favour of the control group. The findings of the long-term effects did not differ from the immediate outcomes (3-month follow up) and the improved level of knowledge acquired and further consolidation of that knowledge did not take place in the 6-month period after the 3-month ePsychNurse.Net course. The ePsychNurse.Net should be further developed and its future modifications will require additional studies, probably with some new outcome measures. PMID- 22672443 TI - Interactive effects of mechanical stress, sand burial and defoliation on growth and mechanical properties in Cynanchum komarovii. AB - In drylands, wind, sand burial and grazing are three important factors affecting growth and mechanical properties of plants, but their interactive effects have not yet been investigated. Plants of the semi-shrub Cynanchum komarovii, common in semi-arid parts of NE Asia, were subjected to brushing, burial and defoliation. We measured biomass allocation and relative increment rates of dry mass (RGR(m)), height (RGR(h)) and basal diameter (RGR(d)). We also measured the stem mechanical properties, Young's modulus (E), second moment of area (I), flexural stiffness (EI) and breaking stress (sigma(b)), and scaled these traits to the whole-plant level to determine the maximum lateral force (F(lateral)) and the buckling safety factor (BSF). Brushing increased RGR(m); neither burial nor defoliation independently affected RGR(m), but together they reduced it. Among buried plants, brushing positively affected stem rigidity and strength through increasing RGR(d), E, I and EI, and at whole plant level this resulted in a larger BSF and F(lateral). However, among unburied plants this pattern was not observed. Our results thus show that effects of mechanical stress and grazing on plants can be strongly modified by burial, and these interactions should be taken into account when considering adaptive significance of plant mechanical traits in drylands. PMID- 22672442 TI - Long-term oncological and continence outcomes after laparoscopic radical prostatectomy: a single-centre experience. AB - Study Type--Therapy (case series) Level of Evidence 4. What's known on the subject? and What does the study add? Over the past decade, minimally invasive laparoscopic radical prostatectomy and more recently robot-assisted laparoscopic prostatectomy have been introduced and have proven equally effective compared with open surgery in terms of mid-term cancer control and complication rates. Because long-term data is lacking, open prostatectomy is still considered the 'gold standard' by some authors, who argue that minimally invasive approaches have to measure up to the excellent long-term results of open surgery. This study represents one of the largest series (1845 patients) of minimally invasive radical prostatectomy with extended follow-up (11.3 years) and detailed data on oncological outcome and postoperative incontinence. It therefore supplies previously lacking information on these details for minimally invasive prostate surgery and provides important information for patient counselling. OBJECTIVE: * To investigate biochemical recurrence (BCR) rates and data on postoperative incontinence in a large laparoscopic radical prostatectomy (LRP) cohort with extended follow-up. MATERIALS AND METHODS: * BCR and independent predictors of BCR were identified using Kaplan-Meier and Cox regression analysis of 1845 patients who underwent LRP from 1999 to 2007. * Urinary incontinence was evaluated by pads per day and stratified as follows: 0-1 pad: no incontinence; 2 3 pads: mild incontinence; and >= 3 pads: severe incontinence. RESULTS: * Organ confined disease, extraprostatic extension, seminal vesicle invasion and lymph node metastasis were present in 71.3%, 20.5%, 6.7% and 3.2% of patients, respectively. The positive surgical margin rate was 29.2%. * Postoperatively, 74.9% of the patients were continent, while 9.2% had mild and 15.9% severe incontinence. * The mean follow-up was 5 years with a maximum follow-up of 11.3 years. * There were 51 overall deaths and six deaths from prostate cancer. The 5 year, 8-year and 10-year BCR-free survival rates were 83.9%, 78.6% and 75.6%, respectively. * On univariate analyses preoperative D'Amico risk classification, pathological tumour stage, postoperative Gleason sum and surgical margin status were predictors of BCR (P < 0.001). * On multivariable analysis, D'Amico classification, Gleason sum (P < 0.001), postoperative tumour stage (P < 0.001), nodal status (P < 0.001) and surgical margin status (P = 0.002) were independent predictors of BCR. CONCLUSIONS: * LRP offers excellent long-term functional and oncological results with a low incidence of BCR for patients with localized disease. * These results could be used for patient counselling before robot assisted laparascopic prostatectomy (RALP) until long-term follow-up data for RALP is available. PMID- 22672444 TI - Successful hair transplantation for treatment of acquired temporal triangular alopecia. PMID- 22672445 TI - Multicomponent venom of the spider Cupiennius salei: a bioanalytical investigation applying different strategies. AB - The multicomponent venom of the spider Cupiennius salei was separated by three different chromatographic strategies to facilitate subsequent analysis of peptidic venom components by tandem mass spectrometry (MALDI-TOF-MS and ESI-MS), Edman degradation and amino acid analysis: (a) desalting of the crude venom by RP HPLC only, (b) chromatographic separation of the crude venom into 42 fractions by RP-HPLC, and (c) multidimensional purification of the crude venom by size exclusion and cation exchange chromatography and RP-HPLC. A total of 286 components were identified in the venom of C. salei by mass spectrometry and the sequence of 49 new peptides was determined de novo by Edman degradation and tandem mass spectrometry; 30 were C-terminally amidated. The novel peptides were assigned to two main groups: (a) short cationic peptides and (b) Cys-containing peptides with the inhibitor cystine knot motif. Bioinformatics revealed a limited number of substantial similarities, namely with the peptides CpTx1 from the spider Cheiracantium punctorium and U3-ctenitoxin-Asp1a from the South American fishing spider (Ancylometes sp.) and with sequences from a Lycosa singoriensis venom gland transcriptome analysis. The results clearly indicate that the quality of the data is strongly dependent on the chosen separation strategy. The combination of orthogonal analytical methods efficiently excludes alkali ion and matrix adducts, provides indispensable information for an unambiguous identification of isomasses, and results in the most comprehensive repertoire of peptides identified in the venom of C. salei so far. PMID- 22672446 TI - Serial magnetic resonance imaging of placenta percreta with bladder involvement during pregnancy and postpartum: a case report. AB - Whether to manage placenta previa percreta surgically or conservatively has been a controversial issue. A 30-year-old woman with placenta percreta with bladder involvement was treated conservatively. A planned cesarean section was performed at 33 weeks' gestation. A 1768-g female infant was delivered through a transverse fundal uterine incision with the placenta left inside the uterus. The following morning, a massive postpartum hemorrhage occurred, and was successfully treated with transarterial embolization. The placenta was never expelled and spontaneously disappeared 4 months after surgery. We demonstrate serial magnetic resonance imaging of the placenta percreta during pregnancy and the postpartum period. PMID- 22672447 TI - Primary anastomosis vs nonrestorative resection for perforated diverticulitis with peritonitis: a prematurely terminated randomized controlled trial. AB - AIM: This randomized controlled trial (RCT) was performed to test the hypothesis that adverse event rates following primary anastomosis (PRA) are not inferior to those following nonrestorative colon resection for perforated diverticulitis with peritonitis. METHOD: Patients admitted for perforated diverticulitis with peritonitis were randomly assigned to PRA (left colon resection with PRA and loop ileostomy) or nonrestorative colon resection (left colon resection with end colostomy). The endpoint was adverse events defined as mortality and morbidity following PRA or nonrestorative colon resection and stoma reversal. The estimated sample size was 300 patients in each study arm (alpha 0.10; 90% power). RESULTS: During a 9-year period, 90 patients were randomly assigned to undergo PRA or nonrestorative colon resection in 14 centres in eight countries. Thirty-four PRA patients were comparable to 56 nonrestorative colon resection patients for age (P = 0.481), gender (P = 0.190), APACHE III (P = 0.281), Hinchey stage III vs IV (P = 0.394) and Mannheim Peritonitis Index (P = 0.145). There were no differences in operating time (P = 0.231), surgeries performed at night (P = 0.083), open vs laparoscopic approach (P = 0.419) and litres of peritoneal irrigation (P = 0.096). There was no significant difference in mortality (2.9 vs 10.7%; P = 0.247) and morbidity (35.3 vs 46.4%; P = 0.38) following PRA or nonrestorative colon resection. After a similar lag time (P = 0.43), 64.7% of PRA patients and 60% of nonrestorative colon resection patients underwent stoma reversal (P = 0.659). Adverse event rates following stoma reversal differed significantly after PRA and reversal of nonrestorative resection (4.5 vs 23.5%; P = 0.0589). CONCLUSION: No conclusions may be drawn on preference of one treatment over another from this RCT because it was prematurely terminated following accrual of 15% of its sample size. PMID- 22672448 TI - Near-infrared imaging of water in human hair. AB - BACKGROUND/PURPOSE: The water content of hair can be evaluated by weighing, the Karl Fischer method, and from electrical properties. However, these methods cannot be used to study the distribution of water in the hair. Imaging techniques are required for this purpose. In this study, a highly sensitive near-infrared (NIR) imaging system was developed for evaluating water in human hair. The results obtained from NIR imaging and conventional methods were compared. METHODS: An extended indium-gallium-arsenide NIR camera (detection range: 1100 2200 nm) and diffuse illumination unit developed in our laboratory were used to obtain a NIR image of hair. A water image was obtained using a 1950-nm interference filter and polarization filter. Changes in the hair water content with relative humidity (20-95% RH) and after immersion in a 7% (w/w) sorbitol solution were measured using the NIR camera and an insulation resistance tester. The changes in the water content after treatment with two types of commercially available shampoo were also measured using the NIR camera. RESULTS: As the water content increased with changes in the relative humidity, the brightness of the water image decreased and the insulation resistance decreased. The brightness in the NIR image of hair treated with sorbitol solution was lower than that in the image of hair treated with water. This shows the sorbitol-treated hair contains more water than water-treated hair. The sorbitol-treated hair had a lower resistance after treatment than before, which also shows that sorbitol treatment increases the water content. With this system, we could detect a difference in the moisturizing effect between two commercially available shampoos. CONCLUSION: The highly sensitive imaging system could be used to study water in human hair. Changes in the water content of hair depended on the relative humidity and treatment with moisturizer. The results obtained using the NIR imaging system were similar to those obtained using a conventional method. Our system could detect differences in the moisturizing effects of two commercially available shampoos. PMID- 22672449 TI - Editorial: 'Face' and its cultural dimensions: some considerations for nurse educators. PMID- 22672450 TI - Acupuncture prior to surgery to minimise postoperative nausea and vomiting: a systematic review. AB - AIMS AND OBJECTIVES: The aim of this systematic review was to assess the outcome of acupuncture treatment prior to surgery in order to avoid or minimise postoperative nausea and vomiting. BACKGROUND: The symptoms of nausea and/or vomiting remain a huge problem for many patients after surgery. There is much debate around the best treatment for nausea and/or vomiting, and the most beneficial solution has yet to be found. Postoperative nausea and vomiting is not a life-threatening symptom, but many patients express great distress and dissatisfaction with the existing treatment. Many patients rate their nausea similar to or worse than pain. Historically, treatments often include drug therapy, but not other non-pharmacologic therapies, such as acupuncture or acupressure, which can have beneficial effects on nausea. DESIGN: A systematic literature review. METHODS: The review was undertaken using key words and electronic databases and included 21 papers from the years November 1996 until August 2009. RESULTS: The results indicate that the application of acupuncture reduced the incidence of nausea but not vomiting when compared with the use of antiemetic prophylaxis alone. CONCLUSIONS: The results show that there is a lack of knowledge of the best treatment to minimise postoperative nausea and vomiting prior to surgery. RELEVANCE TO CLINICAL PRACTICE: The overall results of this review conclude that all kinds of AP stimulation, both non-invasive and invasive, seem to prevent PONV with minimal side effects. The findings from this study can be used to inform future research to evaluate the effects of preoperative treatment with acupuncture vs. sham procedure before surgery to avoid PONV. PMID- 22672451 TI - Factors related to medication non-adherence for patients with hypertension in Taiwan. AB - AIMS AND OBJECTIVE: To characterise a Taiwanese population and to examine the prevalence of antihypertensive medication non-adherence and how the cultural/clinical factors were associated with non-adherence in Taiwan. BACKGROUND: Antihypertensive medication non-adherence is a significant clinical issue in the United States. However, little is known about hypertension (HTN) control and cultural/clinical factors related to non-adherence in Taiwan. DESIGN: A convenience sample survey design was used. METHOD: Data were gathered from a convenience sample of 200 subjects recruited from a large teaching hospital. Medication non-adherence and cultural/clinical factors were recorded using various self-administered questionnaires, and blood pressure was taken twice for each participant. RESULTS: The mean age of the participants was 60.4 (SD 11.5 years) including 62% men. Two-thirds had less than a high school education (64.5%), and the majority of them were married (86.0%) and lived with family or close friends (93.5%). The average length of HTN diagnosis was 8.6 years (SD 9.0 years). Medication non-adherence rate was 47.5%, and uncontrolled HTN rate was 49.0%. Some participants (17.0%) used Chinese herbs for treating their disease (e.g. cough) and promoting health in addition to their regular antihypertensive medications. Two factors were found to be statistically significant for predicting medication non-adherence: Lower Perceived Susceptibility to Specific Diseases [OR = 1.15 (95%CI, 1.01-1.31)] and Longer Length of HTN Diagnosis [OR = 1.06 (95%CI, 1.01-1.12)]. CONCLUSIONS: Taiwanese at risk of non-adherence included those who perceived lower susceptibility to specific diseases and had been diagnosed with HTN for a longer time. Those using herbs need to be studied for an impact of herbs on their adherence behaviour. RELEVANCE TO CLINICAL PRACTICE: These findings can help guide the development of culturally sensitive and clinically appropriate nursing interventions for HTN management in Taiwan. PMID- 22672452 TI - Risk factors and incidence of deep vein thrombosis in lower extremities among critically ill patients. AB - AIMS AND OBJECTIVES: To investigate how many critically ill patients developed deep vein thrombosis (DVT) during their admission to intensive care units (ICU) and to compare the characteristics of patients with and without deep vein thrombosis. BACKGROUND: Critically ill patients are a high-risk group for deep vein thrombosis because they typically have multiple risk factors, such as prolonged immobility, mechanical ventilation and old age. DESIGN: A prospective observational study was employed. METHODS: The subjects were 90 patients who were older than 18 years of age, who were admitted to an intensive care unit for more than five days and were not provided any prophylactic measures. Data were collected at a university hospital for five months. A duplex scan was performed on day 2.4 on average and repeated between days 5-7 to diagnose deep vein thrombosis. The iliac, femoral, popliteal and tibial veins were examined by compression and colour Doppler methods of the duplex scan by one technician. RESULTS: Age, gender and body mass index were significant factors for deep vein thrombosis development (p < 0.05). Ten patients (11.1%) developed deep vein thrombosis during their stay in the intensive care units. CONCLUSIONS: The incidence was lower than in Western studies in which patients were not provided prophylaxis, but may increase with an extended observation period as in previous studies. RELEVANCE TO CLINICAL PRACTICE: The results of this study could allow ICU nurses to recognise the DVT incidence in critically ill patients. This result could lead to more active prevention and monitoring of DVT by ICU nurses, especially for high-risk patients, such as older or obese patients. PMID- 22672453 TI - Needs of adult patients in intensive care units of Estonian hospitals: a questionnaire survey. AB - AIMS AND OBJECTIVES: To describe the intensive care unit patients' perceptions about the importance of their different needs and how their needs are met in Estonian hospitals, and to determine the correlations between the patients' perceptions and their demographic characteristics and background variables. BACKGROUND: Meeting needs of patients in intensive care unit is important for avoiding unpleasant experiences and providing patient-centred care. DESIGN: A descriptive questionnaire survey. METHODS: The study was performed in sixteen intensive care units (ICUs) in six acute care hospitals in Estonia. Data were collected over six months in 2008 using the structured five-point scale questionnaire Needs of Adult Patients in Intensive Care Unit. The Convenience sample consisted of The adult patients discharged from ICUs to hospital wards able to answer the questionnaire (n = 166). Data were analysed using descriptive statistics, correlation analysis and statistical tests. RESULTS: Patients' needs varied and were sometimes unmet. The most important needs were physical comfort and feeling safe. Privacy, involvement of family and friends and being involved in decision-making were less important. The more important a need was perceived to be, the better it was met. The need for physical comfort was met best, involvement in decision-making worst. Patients with lower educational level and unscheduled patients agreed more that their needs were met. The better the patients considered their condition when leaving the ICU, the more they agreed that their needs were met. CONCLUSIONS: The findings provide a basis for understanding the needs of critically ill adults in Estonian ICUs to provide them more patient-centred care and improve their psychological well-being and quality of life after discharge. RELEVANCE TO CLINICAL PRACTICE: Identifying and acknowledging the personal needs of patients in intensive care unit is important. When meeting the patients' needs, their individual characteristics should be taken into consideration. PMID- 22672454 TI - Effect of head and body positioning on cerebral blood flow velocity in patients who underwent cranial surgery. AB - AIM AND OBJECTIVES: The aim of this study was to investigate the effects of head and neck positions on the cerebral blood flow velocity by transcranial Doppler ultrasound in patients who underwent cranial surgery. BACKGROUND: Inappropriate head elevation and body positioning in patients who undergo cranial surgery may affect cerebral blood flow and cerebral perfusion pressure. DESIGNED: Experimental clinical study. METHOD: Our sample consisted of 38 patients who underwent cranial surgery between October 2009 and May 2010. The measurments of mean cerebral blood flow velocity were taken by the transcranial Doppler ultrasound through the temporal window. The mean cerebral blood flow velocity of the patients was measured in supine position with 0 degrees and 30 degrees head elevations, right and left lateral positions, right and left lateral positions with head flexion and extension. The measurements were taken before surgery and within 72 hours after surgery. RESULTS: The mean cerebral blood flow velocity of the middle cerebral arteries was increased in head elevations from 0 degrees to 30 degrees , in right and lateral positions with 30 degrees head elevations, but the velocity was decreased in head flexion and extension positions in preoperative and postoperative periods. DISCUSSION: Head and body positioning, which is one of the nursing care activities, may affect intracranial pressure and cerebral perfusion pressure. Our results are similar with those of previous studies, which showed that head elevation did not affect the cerebral blood flow velocity. RELEVANCE TO CLINICAL PRACTICE: By the results of this study, the head elevation of the patients, who underwent cranial surgery, should be 30 degrees during the nursing care to provide optimum cerebral blood flow. Right and left lateral positioning is safe and recommended for these patients if there is no medical contraindication. PMID- 22672455 TI - Beyond the 'tick and flick': facilitating best practice falls prevention through an action research approach. AB - AIMS AND OBJECTIVES: To examine residential aged care facility staff views on using falls risk assessment tools and the implications for developing falls prevention practices in the context of an action research project. BACKGROUND: Falls risk assessments play an important role in care planning by identifying and monitoring aged care facility residents most at risk of falls. Yet while such assessments are recommended in falls prevention best practice guidelines, there is little published research that examines staff procedures and views related to conducting falls risk assessments. DESIGN: Falls risk assessments were undertaken in the context of an action research project. METHOD: Twelve staff members from two residential aged care facilities (RACFs) in Tasmania formed a single Falls Action Research Group, which met 22 times over a year, providing the study's qualitative data. During this time, key group members assessed 178 residents using a new falls risk assessment tool (FROP-Resi). RESULTS: According to group members, facilities evolved from a 'tick-and-flick' approach to falls risk assessment to a more individualised, face-to-face assessment process. Group members perceived the process to be more meaningful and enjoyable for staff involved in the assessment process resulting in higher quality of assessments and leading to improved levels of falls awareness among staff, residents and family caregivers. CONCLUSIONS: An action research process is useful for facilitating a new approach to falls risk assessments, engaging aged care facility staff with falls prevention and prompting improvements in falls prevention practices. RELEVANCE TO CLINICAL PRACTICE: RACFs need to provide opportunities for staff to meet regularly to discuss practice, identify issues and take action. By doing so, staff can engage meaningfully with best practice activities such as optimising falls risk assessment processes. PMID- 22672456 TI - Visual functioning in nursing home residents: information in client records. AB - AIM AND OBJECTIVES: To improve (eye)care in nursing homes by reporting and assessing visual functioning to enhance professional caregivers' awareness of visual problems. BACKGROUND: Older adults experience visual problems owing to biological ageing or eye disease. In the Netherlands, the prevalence of visual impairments is the highest in the subgroup of nursing home residents (41.3%). These impairments influence quality of life in terms of limiting daily activities and participation in social activities. Furthermore, 63% of visual problems are defined as 'avoidable blindness'. For this reason, screening of visual functioning in the nursing home is of major importance. Moreover, visual functioning should also be taken into account to prevent the incidence of falls. DESIGN: A field study on recorded information of visual functioning and visual assessment in nursing homes. METHODS: Assessment of visual functioning of 259 residents in nursing homes. Subsequently, recorded information in client files is related to the assessment outcome. RESULTS: Only in 101 (39%) of the 259 client records was some information on visual functioning found in client files. Whether a prescription for new glasses was dispensed made no difference in reporting on visual functioning in the client record. In more than half of the cases assessed as 'low vision or blindness', no information about visual functioning was found. Furthermore, no information was found in 31% (80/259) cases of suspected visual problems (referrals). A significant proportion of client records (p < 0.05) showed no recorded information in cases of referral for further check-up. CONCLUSIONS: In this study, one-third of nursing homes residents have visual problems, needing examination by an ophthalmologist. Problems with visual functioning should be assessed and captured in client records. Awareness of residents' visual functioning is a prerequisite for adapting basic daily care to the residents' needs. PMID- 22672457 TI - A systematic review of peer support interventions for breastfeeding. AB - AIMS AND OBJECTIVES: The objective of this systematic review was to describe peer support interventions supporting breastfeeding during pregnancy and the postnatal period. BACKGROUND: Breastfeeding is an effective way to promote infants' health. Including a peer support element in breastfeeding programmes is a highly successful way to increase breastfeeding. DESIGN: A systematic literature review. METHODS: The review was conducted from the CINAHL, MEDLINE and the Cochrane Library databases from year 2000 until the end of February 2008. According to the inclusion criteria, the adopted studies focused on breastfeeding, breastfeeding support interventions and education of healthy mothers and infants from the perspective of mothers or family members. Additionally, the studies had to be conducted in Europe, North America, Australia or New Zealand to meet the criteria. Articles combining peer support and professional support were also included in the study. RESULTS: The results indicated that during pregnancy, hospitalisation and the postnatal period, individual support and education were used most commonly. Peer support was strongly associated with the postnatal period. The combination of professional support and peer support by trained and experienced peer supporters was effective in ensuring the continuation of breastfeeding. CONCLUSIONS: Only continuous breastfeeding support produces effective results. Diverse types of interventions are needed during different phases of motherhood. The role of peer support is most important during the postnatal period. If professional support is not available for mothers, peer support could provide an alternative worth considering. RELEVANCE TO CLINICAL PRACTICE: Professionals require breastfeeding education to act as breastfeeding supporters as well as the support of their organisations in this work. Moreover, professionals need to gain knowledge of the role of peer support regarding the efficient combination of professional support and peer support to increase breastfeeding. PMID- 22672458 TI - Services doing the best they can: service experiences of young adults with type 1 diabetes mellitus in rural Australia. AB - AIMS AND OBJECTIVES: To describe the healthcare experiences of young adults with type 1 diabetes who access diabetes services in rural areas of New South Wales, Australia. BACKGROUND: The incidence of type 1 diabetes in childhood and adolescence is increasing worldwide; internationally, difficulties are encountered in supporting young people during their transition from children to adulthood. Consumers' experiences and views will be essential to inform service redesign. DESIGN: This was a qualitative exploratory study. METHODS: Semistructured telephone interviews were conducted with 26 people aged 18-28 years living rurally, recruited through staff in four regional healthcare centres in 2008. RESULTS: Two key themes were evident: lack of access (comprised of transfer to adult services, access to health professionals and access to up-to date information) and age-appropriate provision. The impact of place of residence and personal motivation crossed all themes. Participants contrasted unfavourably the seamless care and support received from paediatric outreach services with the shortages in specialist and general practice-based care and information and practical problems of service fragmentation and lack of coordination experienced as adults. They identified a range of issues including need for ongoing education, age-appropriate services and support networks related to developing their ability to self-manage. They valued personal service; online and electronic support was seldom volunteered as an alternative. CONCLUSION: This was a first view of rural young people's experiences with adult diabetes services. Reported experiences were in line with previous reports from other settings in that they did not perceive services in this rural area of Australia as meeting their needs; suggestions for service redesign differed. RELEVANCE TO CLINICAL PRACTICE: New models of age-appropriate service provision are required, to meet their needs for personal as well as other forms of support, whilst acknowledging the very real resource limitations of these locations. PMID- 22672459 TI - Perceptions of effective self-care support for children and young people with long-term conditions. AB - AIMS AND OBJECTIVES: To: (1) Examine children's/young people's, parents' and professionals'/workers' perceptions of the effectiveness of different models of self-care support, (2) identify factors that support and inhibit self-care and (3) explore how different models integrate with self-care support provided by other organisations. BACKGROUND: Childhood long-term illness has been largely overlooked in government policy and self-care support under-researched when compared with adults. There is a lack of evidence on which are the most appropriate models and methods to engage young people and their parents in self care. DESIGN: Case study. METHODS: Case studies of six different models of self care support were conducted using multiple methods of data collection in 2009. Semi-structured interviews were conducted with 26 young people, 31 parents and 36 self-care support providers. A sample of self-care support activities was observed and relevant documents reviewed. Data were analysed using the Framework approach. RESULTS: The effectiveness of self-care support projects was defined in relation to four dimensions - providing a sense of community, promoting independence and confidence, developing knowledge and skills and engaging children/young people. Self-care support provided by schools appeared to be variable with some participants experiencing barriers to self-management and inclusion. Participants self-referred themselves to self-care support projects, and there was a lack of integration between some projects and other forms self care support. CONCLUSION: This study adds to knowledge by identifying four dimensions that are perceived to be central to effective self-care support and the contextual factors that appear to influence access and experiences of self care support. RELEVANCE TO CLINICAL PRACTICE: Study findings can inform the development of self-care support programmes to meet the needs of individuals, families and communities. In addition, the findings suggest that healthcare professionals need to support schools if young people with long-term conditions are to have the same educational and social opportunities as their peers. PMID- 22672460 TI - Sexual self-concept as influencing intended sexual health behaviour of young adolescent Taiwanese girls. AB - AIMS AND OBJECTIVES: The purpose of this study was to test a process model that assesses the relationship of sexual health knowledge and normative beliefs to sexual health behavioural intention, with sexual self-concept as a mediating variable. The model is intended to assist in the prediction of which adolescents would exhibit a lower intention to engage in protective sexual health behaviour. BACKGROUND: Previous research has shown that sexual-related behaviours are associated with sexual self-concept, sexual health knowledge and perceived parental/peer approval of sexual behaviour. DESIGN: This study is a cross sectional research. METHODS: This study was conducted with 545 adolescent girls, aged 12-15 years, from eight junior high schools in Taiwan. Participants were assessed using the Sexual Self-Concept Inventory, the Sexual Health Behavior Intention Scale, the Parental Approval of Sexual Behavior Scale (PASB), the Friends' Approval of Sexual Behavior Scale and the Sexual Health Knowledge Scale. Data were analysed using structural equation modelling, with the maximum likelihood estimate determined by the LISREL 8.52 program. RESULTS: The model exhibited adequate fit (goodness-of-fit index = 0.96, adjusted goodness-of-fit index = 0.94, normed fit index = 0.96, comparative fit index = 0.98, standardised root mean square residual = 0.049 and root mean square error of approximation = 0.048) and the findings indicate that sexual self-concept was a significant influence on the relationship of sexual health knowledge and normative beliefs to sexual health behavioural intention. CONCLUSIONS: The results of this study revealed the importance of sexual self-concept for adolescent girls' sexual health behaviour. RELEVANCE TO CLINICAL PRACTICE: Evidence-based strategies that reinforce and clarify sexual self-concept as a mediating factor may aid in adolescent females' intention to engage in protective sexual health behaviour. PMID- 22672461 TI - Developing empathy in nursing students: a cohort longitudinal study. AB - AIMS AND OBJECTIVES: To determine whether a specific training course will enhance empathic skills in student nurses during a 3-year degree course. The study considers levels of empathy in student nurses and assesses whether these can be increased. BACKGROUND: Empathy is accepted as a critical component of supportive relationships. Many scholars have argued that empathy provides health professionals with the capacity to improve the health of patients, so it should ideally be taught to make health professionals more responsive to patient needs. DESIGN: Cohort longitudinal study. METHODS: Data were collected using the Italian version of the Balanced Emotional Empathy Scale (BEES). The study was designed to guarantee repeated measurements of levels of emotional empathy in the pre- and postintervention phases. This allowed us to evaluate the development and improvement of empathy and to measure the effects of extra training on the students' empathy skills. Two groups took part in the study: the Intervention and the Control Groups. Students in the Intervention Group attended additional seminars and laboratories in small groups with tutors to learn and develop communicative and empathic abilities. RESULTS: One hundred and three participants (76% women) completed the study. Data showed that the training course was effective, especially for women: BEES scores 31.60 at pre-intervention phase and 42.91 at the end of the academic course. Results regarding men were less clear, and the study discusses these unexpected, anomalous findings. CONCLUSION: According to literature, men and women have different empathic traits, and we found that they show disparate empathic tendencies. More women than men took advantage of the training course. In any case, our data show that specific training courses are effective. RELEVANCE TO CLINICAL PRACTICE: As our study shows, empathy is a skill that may be taught. So it would be advisable to introduce these into the traditional nursing curriculum. PMID- 22672462 TI - Exploring nurses' experiences of prescribing in secondary care: informing future education and practice. AB - AIMS AND OBJECTIVES: To explore the experiences of secondary care nurse prescribers to establish how prescribing is employed and what its benefits and disadvantages are perceived to be. BACKGROUND: Nurse prescribing has developed rapidly since it inception almost 20 years ago and there is a significant body of research evaluating its implementation in primary care. Recent expansion of non medical prescribing rights has prompted nurses in secondary care establishments to become prescribers. Evaluation of nurse prescribing in this new environment is required, if practice is to be informed and advanced. The lack of such evaluations in the published literature was the impetus for this study. DESIGN: A cross-sectional qualitative study. METHODS: A convenience sample of nurse prescribers was interviewed using a single broad question to prompt elaboration. Transcribed interviews were analysed using Colaizzi's procedural steps. RESULTS: Three main themes emerged from the analysis: motivations behind becoming a nurse prescriber; benefits and limitations of prescribing education and continuing professional development and prescribing in practice. CONCLUSION: Nurses felt nurse prescribing offers clear benefits in relation to patient care. Where nurses were not prescribing, finance arrangements between different NHS trusts appear to be a significant barrier to its successful implementation of prescribing in practice. Nurse prescribing is strongly believed to be the domain of the experienced nurse. There is a clear need for ongoing evaluation of all aspects of nurse prescribing. RELEVANCE TO CLINICAL PRACTICE: This paper makes key recommendations on the future development and delivery of programmes of education for nurse prescribers and for the delivery of safe and effective prescribing in practice. PMID- 22672463 TI - Surviving, not thriving: a qualitative study of newly qualified midwives' experience of their transition to practice. AB - AIM AND OBJECTIVES: The study explored the experiences of newly qualified midwives and described the factors that facilitated or constrained their development during the transition from student to registered midwife. BACKGROUND: Knowledge of the transition to midwifery practice remains limited. DESIGN AND METHOD: A qualitative descriptive approach was used. Sixteen graduates from one Australian University participated in a tape-recorded interview. Thematic analysis was used to analyse the data set. RESULTS: The metaphor of 'The Pond', an environment that consists of layers of life and can be both clear and peaceful or murky and infested, was used to describe new midwives perceptions of the context and culture of hospital-based maternity care. For some, 'The Pond' was a harsh environment that often became toxic. The 'Life-raft' metaphor was used to describe the importance of midwife-to-midwife relationships. The theme of 'Swimming' captured the consequence of positive interactions with colleagues and a supportive environment, whilst 'Sinking' described the consequence of poor relationships with midwives and a difficult working environment. CONCLUSION: The study highlights the importance of positive midwife-to-midwife relationships on the transition from student to registered midwife. There was also evidence that continuity with women and midwifery colleagues enhanced confidence and restored faith in normal birth. At the same time, it was clear that the midwifery culture of some institutions remains highly contested with midwives struggling to provide woman-centred care and often challenged by the risk-averse nature of maternity care. RELEVANCE TO CLINICAL PRACTICE: Whilst further work is required, the findings provide a deeper understanding of individual midwives' transition period. The importance of forming longitudinal relationships not only with women but with midwifery colleagues is highlighted. Developing continuity models that adequately support graduates and student's needs are likely to assist in addressing practices issues in both the academic and clinical setting. PMID- 22672464 TI - Becoming a caregiver: new family carers' experience during the transition from hospital to home. AB - AIMS AND OBJECTIVES: To explore and understand the experience of new informal caregivers in Italy during the transition from hospital to home. BACKGROUND: Frequent patient discharge into the home environment has lead to a significant increase in postdischarge care being provided by family caregivers. The transition period in particular is seen as a period of great significance, as caregivers may be unprepared and concerned as to the amount of care required by the recipient. DESIGN: A qualitative phenomenological approach was used to gain a deeper understanding of caregivers' lived experiences. METHODS: Data were collected at two points in time using different methodologies: in-depth interviews were conducted to explore the caregivers' perspective of the predischarge period; focus groups obtained data after the patients' re-entry into the home environment and aimed to validate interview findings. RESULTS: Family caregivers reflected on three main themes during the transition period: (1) their newly acquired role; (2) the recipient's condition; and (3) the support they required. The core concept of 'being responsible for everything' seemed to be a recurring theme running through these three subject matters. Fulfilling numerous commitments and different social roles besides the caring activity itself seemed to weigh heavily on caregivers. Carers were referring particularly to their need for hope, confidence and safety during the transition from hospital to home. CONCLUSIONS: It cannot be assumed a priori that families can cope with the demands of care-giving. Therefore, healthcare professionals should come to recognise caregivers as persons in need of emotional and practical support. RELEVANCE TO CLINICAL PRACTICE: The findings of this study can stimulate healthcare professionals to acquire effective communication skills and display an empathic attitude when assessing caregivers' needs in the particularly challenging phase of transition from hospital to home. PMID- 22672465 TI - Attitudes of healthcare staff and patients' family members towards family presence during resuscitation in adult critical care units. AB - AIM AND OBJECTIVES: This study examines the attitudes of healthcare staff and patients' family members towards family presence during resuscitation (FPDR) in critical care units in Hong Kong. BACKGROUND: A wealth of literature is available on FPDR in various hospital and healthcare settings. The findings include many anecdotal accounts of both the positive and the negative effects of family presence. There is little documentation on the comparisons of staff and family members' perceptions and the predictors of staff attitudes towards FPDR practice. DESIGN: Cross-sectional survey design. METHOD: A convenience sample of 163 healthcare staff and 69 family members was recruited from the intensive care units. RESULTS: There was significant difference in the attitudes of healthcare staff and patients' families towards FPDR. The regression analysis showed that the healthcare staff would be more supportive to FPDR if family members could share the dying moments with patients, family members were accompanied by a bereavement team member, there was adequate staff to support the family and staff members were adequately trained. If healthcare staff feel that family members may have the impression that the resuscitation is chaotic, witness resuscitation is traumatic experience for the family, family presence will increase risk of litigation and colleagues will not allow family members to stay during resuscitation making them less supportive of FPDR. Nurses were more supportive to FPDR than doctors. CONCLUSION: The results provide information for healthcare professionals on the development of FPDR programmes for patients and their family members. Through multi-disciplinary collaborations, the effective and safe implementation of FPDR practice can be enhanced. RELEVANCE TO CLINICAL PRACTICE: The results could help the clinical staff to develop written guidelines to produce an integrated and consistent approach to this sensitive issue in clinical practice. PMID- 22672466 TI - Reliability and validity of the Chinese version of heart disease fact questionnaire. PMID- 22672467 TI - Effect of oestrogen receptors on brain NMDA receptors of 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine mice. AB - Parkinson's disease (PD) is characterised by the loss of nigrostriatal dopamine (DA) neurones and glutamate overactivity. There is substantial evidence to suggest that oestrogens prevent or delay the disease. 17beta-oestradiol has neuroprotective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD and modulates brain NMDA receptors. In MPTP-lesioned mice, oestrogen receptor (ER)alpha and ERbeta are important in 17beta-oestradiol induced neuroprotection. To evaluate the role of ERs in the response of NMDA receptors to lesion, we compared wild-type (WT) with ER knockout (KO) C57Bl/6 male mice that received 7, 9 or 11 mg/kg of MPTP. These mice were also treated with MPTP (9 mg/kg) and 17beta-oestradiol. [(3) H]Ro 25-6981 specific binding autoradiography was used to label NMDA receptors containing NR2B subunits. In the frontal and cingulate cortex and striatum, vehicle-treated WT mice had higher [(3) H]Ro 25-6981 specific binding compared to ERKO mice. Cortical [(3) H]Ro 25 6981 specific binding decreased with increasing doses of MPTP in WT and ERKOalpha but not ERKObeta mice, whereas a dose-related decrease was only observed in the striatum of WT mice remaining low in ERKOalpha and ERKObeta mice. No effect of 17beta-oestradiol treatment in intact or MPTP-lesioned mice of all three genotypes was observed in the cortex, whereas it increased striatal specific binding of intact ERKObeta and MPTP-lesioned WT mice. Striatal [(3) H]Ro 25-6981 specific binding positively correlated with striatal DA concentrations only in WT mice. MPTP and 17beta-oestradiol treatments had more limited effects in the hippocampus. Only in the CA3 and dentate gyrus did vehicle and 17beta-oestradiol treated ERKOalpha mice have higher [(3) H]Ro 25-6981 specific binding than WT and ERKObeta mice, whereas MPTP decreased this specific binding only in the CA1, CA2 and CA3 of ERKOalpha mice. Hence, brain NMDA receptors were affected by the deletion of ERs, which affect the response to MPTP and 17beta-oestradiol treatments with brain region specificity. PMID- 22672468 TI - Validation of the Korean version of the Eppendorf Schizophrenia Inventory as a screening measure to detect adolescents at ultra-high risk for psychosis. AB - AIM: No validated self-report scale is available for use as a screening tool to detect non-help-seeking adolescents at ultra-high risk (UHR) for psychosis in a community setting. The study aims to examine the reliability and validity of the Korean version of the Eppendorf Schizophrenia Inventory (K-ESI) for assessing adolescents at UHR for psychosis in a community setting. METHODS: In the first study, to confirm the reliability and discriminant validity of the K-ESI, community sample (782 adolescents, 281 young adults, 122 early and middle-aged adults) and outpatients with schizophrenia (109) were recruited. A single cross sectional survey was performed using the K-ESI for the community sample and the K ESI and Positive and Negative Syndrome Scale for patients. In the second study, the Korean version of Youth Self Report (K-YSR) was administered initially to 1002 students. Of the 217 students whose scores were equal to or higher than the cut-off point of the K-YSR, 120 who agreed to an in-depth evaluation were interviewed using the Comprehensive Assessment of At-Risk Mental States to confirm the predictive validity of the K-ESI. RESULTS: The K-ESI showed good internal consistency and excellent test-retest reliability and discriminant validity. However, the factor structure in adolescents was substantially different from that of the original ESI. The best cut-off point for the K-ESI to identify UHR adolescents was 29, with a sensitivity of 77% and a specificity of 70%. CONCLUSION: The results revealed that the K-ESI can be used as a valid and reliable instrument to identify adolescents at UHR for psychosis in a community setting. PMID- 22672469 TI - Penetration of anticancer drugs through tumour tissue as a function of cellular packing density and interstitial fluid pressure and its modification by bortezomib. AB - BACKGROUND: Limited penetration of anticancer drugs in solid tumours is a probable cause of drug resistance. Our previous results indicate that drug penetration depends on cellular packing density and adhesion between cancer cells. METHODS: We used epithelioid and round cell variants of the HCT-8 human colon carcinoma cell lines to generate tightly and loosely packed xenografts in nude mice. We measured packing density and interstitial fluid pressure (IFP) and studied the penetration of anti-cancer drugs through multilayered cell cultures (MCC) derived from epithelioid HCT-8 variants, and the distribution of doxorubicin in xenografts with and without pre-treatment with bortezomib. RESULTS: We show lower packing density in xenografts established from round cell than epithelioid cell lines, with lower IFP in xenografts. There was better distribution of doxorubicin in xenografts grown from round cell variants, consistent with previous data in MCC. Bortezomib pre-treatment reduced cellular packing density, improved penetration, and enhanced cytotoxcity of several anticancer drugs in MCC derived from epithelioid cell lines. Pre-treatment of xenografts with bortezomib enhanced the distribution of doxorubicin within them. CONCLUSIONS: Our results provide a rationale for further investigation of agents that enhance the distribution of chemotherapeutic drugs in combination with conventional chemotherapy in solid tumours. PMID- 22672470 TI - Residual thermal stress simulation in three-dimensional molar crown systems: a finite element analysis. AB - PURPOSE: To simulate coefficient of thermal expansion (CTE)-generated stress fields in monolithic metal and ceramic crowns, and CTE mismatch stresses between metal, alumina, or zirconia cores and veneer layered crowns when cooled from high temperature processing. MATERIALS AND METHODS: A 3D computer-aided design model of a mandibular first molar crown was generated. Tooth preparation comprised reduction of proximal walls by 1.5 mm and of occlusal surfaces by 2.0 mm. Crown systems were monolithic (all-porcelain, alumina, metal, or zirconia) or subdivided into a core (metallic, zirconia, or alumina) and a porcelain veneer layer. The model was thermally loaded from 900 degrees C to 25 degrees C. A finite element mesh of three nodes per edge and a first/last node interval ratio of 1 was used, resulting in approximately 60,000 elements for both solids. Regions and values of maximum principal stress at the core and veneer layers were determined through 3D graphs and software output. RESULTS: The metal-porcelain and zirconia-porcelain systems showed compressive fields within the veneer cusp bulk, whereas alumina-porcelain presented tensile fields. At the core/veneer interface, compressive fields were observed for the metal-porcelain system, slightly tensile for the zirconia-porcelain, and higher tensile stress magnitudes for the alumina-porcelain. Increasingly compressive stresses were observed for the metal, alumina, zirconia, and all-porcelain monolithic systems. CONCLUSIONS: Variations in residual thermal stress levels were observed between bilayered and single-material systems due to the interaction between crown configuration and material properties. PMID- 22672471 TI - Evaluating quality of care for patients with type 2 diabetes using electronic health record information in Mexico. AB - BACKGROUND: Several low and middle-income countries are implementing electronic health records (EHR). In the near future, EHRs could become an efficient tool to evaluate healthcare performance if appropriate indicators are developed. The aims of this study are: a) to develop quality of care indicators (QCIs) for type 2 diabetes (T2DM) in the Mexican Institute of Social Security (IMSS) health system; b) to determine the feasibility of constructing QCIs using the IMSS EHR data; and c) to evaluate the quality of care (QC) provided to IMSS patients with T2DM. METHODS: We used a three-stage mixed methods approach: a) development of QCIs following the RAND-UCLA method; b) EHR data extraction and construction of indicators; c) QC evaluation using EHR data from 25,130 T2DM patients who received care in 2009. RESULTS: We developed 18 QCIs, of which 14 were possible to construct using available EHR data. QCIs comprised both process of care and health outcomes. Several flaws in the EHR design and quality of data were identified. The indicators of process and outcomes of care suggested areas for improvement. For example, only 13.0% of patients were referred to an ophthalmologist; 3.9% received nutritional counseling; 63.2% of overweight/obese patients were prescribed metformin, and only 23% had HbA1c <7% (or plasma glucose<=130 mg/dl). CONCLUSIONS: EHR data can be used to evaluate QC. The results identified both strengths and weaknesses in the electronic information system as well as in the process and outcomes of T2DM care at IMSS. This information can be used to guide targeted interventions to improve QC. PMID- 22672472 TI - A primary pericardial undifferentiated sarcoma invading the right atrium and superior vena cava. AB - Primary undifferentiated cardiac sarcomas are rare. The literature demonstrated that 81% of primary cardiac undifferentiated sarcomas arose in the left atrium. We reported herein a case of 56-year-old male farmer with a primary pericardial undifferentiated sarcoma, which was revealed only on echocardiography but not computed tomography. The tumor, which invaded the right atrium and superior vena cava, was not completely resected. PMID- 22672473 TI - Effect of experimental feed additives on aflatoxin in milk of dairy cows fed aflatoxin-contaminated diets. AB - Three studies were conducted to determine the potential of experimental feed additives (EFAs), clays or non-digestible yeast oligosaccharides, to reduce milk aflatoxin (AFM1) concentrations in lactating Holstein cows consuming aflatoxin contaminated diets. All studies included a pre-treatment period and a 2-week experimental period in a randomized block design. During the pre-treatment period, cows received a total mixed ration (TMR) with no aflatoxin contamination. During both experimental weeks, all cows were fed a TMR containing aflatoxin contaminated corn. During experimental week 1, cows received no EFA's in the TMR, but EFA's were included in the TMR for the second experimental week. In studies 1 and 2, the experimental period consisted of 2 weeks each lasting 7 days with 12 cows per treatment. Aflatoxin M1 concentrations were analysed by HPLC for milk samples collected on days 5-7 and days 11-14. In various experiments, treatments included control (no EFA), 100 g/cow daily of experimental Lallemand((r)) product, 10 g/cow daily of MTB-100((r)) -2004, (Alltech, Inc.), 10 g/cow daily of MTB-100((r)) -2006, (Alltech, Inc.), 10 g/cow daily of experimental Alltech((r)) product (Alltech, Inc.) and 227 g/cow daily of Astra-Ben 20((r)) (AB-20((r)) ; Prince Agri Products, Inc.). In study 3, the experimental period of 2 weeks each lasting 8 days and milk samples were collected from day 4 to 8 and day 11 to 16. Milk samples from study 3 were analysed for AFM1 concentrations by ELISA. For all experiments, changes in AFM1 concentrations because of the addition of EFA's were calculated. Four of the five EFAs tested in this study had no significant effect on AFM1 concentrations. However, the addition of AB-20((r)) resulted in a significant decrease in AFM1 concentrations (60.4%). In summary, the addition of AB-20((r)) to the diet of cattle appears to be effective for significantly reducing AFM1 concentrations in the milk of cows fed an aflatoxin-contaminated diet. PMID- 22672474 TI - Intrinsic and extrinsic negative regulators of nuclear protein transport processes. AB - The nuclear-cytoplasmic protein transport is a critical process in cellular events. The identification of transport signals (nuclear localization signal and nuclear export signal) and their receptors has facilitated our understanding of this expanding field. Nuclear transport must be appropriately regulated to deliver proteins through the nuclear pore when their functions are required in the nucleus, and to export them into the cytoplasm when they are not needed in the nucleus. Altered nuclear transport processes have been observed in stressed cells, which would change gene expressions. Some viruses interfere with nuclear transport in host cells to evade immune defense. Moreover, certain transport factors negatively regulate nuclear protein transport in cells. Understanding the regulatory mechanisms of nuclear-cytoplasmic trafficking not only provides important information about cellular processes, but also is of use for developing specific inhibitors for transport pathways. PMID- 22672476 TI - Mucopolysaccharidosis type I (Hurler syndrome) and anesthesia: the impact of bone marrow transplantation, enzyme replacement therapy, and fiberoptic intubation on airway management. AB - AIM: To assess the effect of bone marrow transplantation (BMT), enzyme replacement therapy (ERT), and a fiberoptic endotracheal intubation technique in patients with mucopolysaccharidosis type I (MPS I, Hurler syndrome). BACKGROUND: The mucopolysaccharidoses are inherited metabolic conditions with a well documented association with difficult airway management. We present the largest series to date of patients with Hurler syndrome (MPS I) and look at the impact of new treatments, such as BMT and ERT, on anesthesia and airway management. METHODS/MATERIALS: We carried out a retrospective chart review of patients with MPSI undergoing anesthesia over 9 years at the Royal Manchester Children's Hospital. Data were collected on incidence of difficult and failed intubation and airway difficulties under anesthesia. RESULTS: There were 39 patients identified, of which 20 had the attenuated form of MPS I and received ERT, 18 were treated by BMT and one patient received neither treatment. These patients had a total of 114 general anesthetics for 141 procedures. The incidence of airway complications overall is lower than previously reported at 31%. Patients with the attenuated form of the disease on ERT still have a high incidence of airway problems at 57% and a failed intubation rate of 3%. BMT patients on the other hand have a much lower incidence of airway complications at 14%, and there were no failed intubations in this group. CONCLUSIONS: Managing the MPS1 patient continues to be a challenge but with treatment and newer forms of airway management it is improving. PMID- 22672475 TI - Anti-staphylococcal activities of lysostaphin and LytM catalytic domain. AB - BACKGROUND: Lysostaphin and the catalytic domain of LytM cleave pentaglycine crossbridges of Staphylococcus aureus peptidoglycan. The bacteriocin lysostaphin is secreted by Staphylococcus simulans biovar staphylolyticus and directed against the cell walls of competing S. aureus. LytM is produced by S. aureus as a latent autolysin and can be activated in vitro by the removal of an N-terminal domain and occluding region. RESULTS: We compared the efficacies of the lysostaphin and LytM catalytic domains using a newly developed model of chronic S. aureus infected eczema. Lysostaphin was effective, like in other models. In contrast, LytM was not significantly better than control. The different treatment outcomes could be correlated with in vitro properties of the proteins, including proteolytic stability, affinity to cell wall components other than peptidoglycan, and sensitivity to the ionic milieu. CONCLUSIONS: Although lysostaphin and LytM cleave the same peptide bond in the peptidoglycan, the two enzymes have very different environmental requirements what is reflected in their contrasting performance in mouse eczema model. PMID- 22672477 TI - Human leukocyte antigen mismatches associated with increased risk of rejection, graft failure, and death independent of initial immunosuppression in renal transplant recipients. AB - Human leukocyte antigen (HLA) mismatches have been shown to adversely affect renal allograft outcomes and remain an important component of the allocation of deceased donor (DD) kidneys. The ongoing importance of HLA mismatches on transplant outcomes in the era of more potent immunosuppression remains debatable. Using Australia and New Zealand Dialysis and Transplant Registry, live and DD renal transplant recipients between 1998 and 2009 were examined. The association between the number of HLA mismatches and HLA-loci mismatches and outcomes were examined. Of the 8036 renal transplant recipients, 59% had between 2 and 4 HLA mismatches. Compared with 0 HLA mismatch, increasing HLA mismatches were associated with a higher risk of graft failure and patient death in the adjusted models. HLA mismatches were associated with an incremental risk of rejection although the relative risk was higher for live donor kidney transplants. Increasing HLA-AB and HLA-DR mismatches were associated with a greater risk of acute rejection, graft failure, death-censored graft failure, and/or death. There was no consistent association between initial immunosuppressive regimen and outcomes. Our results corroborate and extend the previous registry analyses demonstrating that HLA mismatches are associated with poorer transplant outcomes independent of immunosuppression and transplant era. PMID- 22672478 TI - Sperm storage in caecilian amphibians. AB - BACKGROUND: Female sperm storage has evolved independently multiple times among vertebrates to control reproduction in response to the environment. In internally fertilising amphibians, female salamanders store sperm in cloacal spermathecae, whereas among anurans sperm storage in oviducts is known only in tailed frogs. Facilitated through extensive field sampling following historical observations we tested for sperm storing structures in the female urogenital tract of fossorial, tropical caecilian amphibians. FINDINGS: In the oviparous Ichthyophis cf. kohtaoensis, aggregated sperm were present in a distinct region of the posterior oviduct but not in the cloaca in six out of seven vitellogenic females prior to oviposition. Spermatozoa were found most abundantly between the mucosal folds. In relation to the reproductive status decreased amounts of sperm were present in gravid females compared to pre-ovulatory females. Sperm were absent in females past oviposition. CONCLUSIONS: Our findings indicate short-term oviductal sperm storage in the oviparous Ichthyophis cf. kohtaoensis. We assume that in female caecilians exhibiting high levels of parental investment sperm storage has evolved in order to optimally coordinate reproductive events and to increase fitness. PMID- 22672479 TI - Is a treatment delay in radical prostatectomy safe in individuals with low-risk prostate cancer? AB - INTRODUCTION: Many patients diagnosed with localized prostate cancer (PCa) are presented with several treatment modalities, which may require time to understand these options before making an informed decision regarding treatment. AIM: The aim of this study was to compare the effect of radical prostatectomy (RP) delay on postoperative functional outcomes and mortality in a North American population based cohort. METHODS: Overall, 17,153 men treated with RP for non-metastatic clinical stage T1-2, low-grade PCa between years 1995 and 2005 within the U.S. Surveillance, Epidemiology, and End Results Medicare-linked database were abstracted. MAIN OUTCOME MEASURES: The effect of treatment delay (from PCa diagnosis to RP of >3 months) on pathological upstaging at surgery (>=pT3) and postoperative functional outcomes (urinary incontinence and erectile dysfunction) was examined using logistic regression analyses. The 10-year PCa mortality rates were computed using cumulative incidence rates. RESULTS: Overall, 2,576 (15%) patients underwent RP > 3 months after diagnosis. A treatment delay of >3 months was associated with a 24% and 33% higher rate of erectile dysfunction diagnosis and procedure, respectively (both P <= 0.001). Treatment delay was also associated with 6% higher rate of urinary incontinence procedure (P = 0.01). Furthermore, a dose-response effect was detected with respect to increasing durations of RP delay (<=3 vs. 3-5 vs. 5-9 vs. >=9 months) the rates of erectile dysfunction and urinary incontinence diagnoses/procedures. Treatment delay was not associated with pathological upstaging and PCa mortality. CONCLUSIONS: Customarily, the timing of RP following biopsy is dictated by tumor aggressiveness. In general, patients with more unfavorable characteristics are operated sooner. This may obliterate the potential detriments of delayed RP. The treatment delay between biopsy and RP may result in more extensive periprostatic tissue resection and may adversely affect postoperative continence and erectile function. PMID- 22672480 TI - Causes of mental distress do matter. PMID- 22672481 TI - The prevention access and risk taking in young people (PARTY) project protocol: a cluster randomised controlled trial of health risk screening and motivational interviewing for young people presenting to general practice. AB - BACKGROUND: There are growing worldwide concerns about the ability of primary health care systems to manage the major burden of illness in young people. Over two thirds of premature adult deaths result from risks that manifest in adolescence, including injury, neuropsychiatric problems and consequences of risky behaviours. One policy response is to better reorientate primary health services towards prevention and early intervention. Currently, however, there is insufficient evidence to support this recommendation for young people. This paper describes the design and implementation of a trial testing an intervention to promote psychosocial risk screening of all young people attending general practice and to respond to identified risks using motivational interviewing. MAIN OUTCOMES: clinicians' detection of risk-taking and emotional distress, young people's intention to change and reduction of risk taking. SECONDARY OUTCOMES: pathways to care, trust in the clinician and likelihood of returning for future visits. The design of the economic and process evaluation are not detailed in this protocol. METHODS: PARTY is a cluster randomised trial recruiting 42 general practices in Victoria, Australia. Baseline measures include: youth friendly practice characteristics; practice staff's self-perceived competency in young people's care and clinicians' detection and response to risk taking behaviours and emotional distress in 14-24 year olds, attending the practice. Practices are then stratified by a social disadvantage index and billing methods and randomised. Intervention practices receive: nine hours of training and tools; feedback of their baseline data and two practice visits over six weeks. Comparison practices receive a three hour seminar in youth friendly practice only. Six weeks post-intervention, 30 consecutive young people are interviewed post-consultation from each practice and followed-up for self-reported risk taking behaviour and emotional distress three and 12 months post consultation. DISCUSSION: The PARTY trial is the first to examine the effectiveness and efficiency of a psychosocial risk screening and counselling intervention for young people attending primary care. It will provide important data on health risk profiles of young people attending general practice and on the effects of the intervention on engagement with primary care and health outcomes over 12 months. TRIAL REGISTRATION: ISRCTN16059206. PMID- 22672482 TI - ADAMTS-13 activity and autoantibodies classes and subclasses as prognostic predictors in acquired thrombotic thrombocytopenic purpura. AB - BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a rare life-threatening disease. Of surviving patients, 45% develops an exacerbation or a late recurrence. Severe ADAMTS-13 deficiency, both during the acute episode and remission, is a well-established predictor of recurrence. The predictive value of anti-ADAMTS-13 antibodies, their inhibitory activity and Ig class subtype for disease recurrence is still to be established. OBJECTIVES: To analyze ADAMTS-13 related biomarkers (ADAMTS-13 and anti-ADAMTS-13 immunoglobulins, classes and subclasses) and their potential relationship with prognosis. PATIENTS/METHODS: In 115 patients with TTP, we assessed the association between levels of these biomarkers and the severity of acute episodes; we analysed also the hazard ratio (HR) and 95% confidence interval (CI) of recurrence in association with biomarkers levels retrieved at the previous acute episode or during remission, using Cox regression models. RESULTS: During the acute phase, higher IgA, IgG1 and IgG3 titers showed the strongest association with acute episode severity. In the survival analyzes, the only biomarker significantly associated with a high hazard of recurrence after an acute episode was the presence of IgG. Conversly, low ADAMTS-13 activity or antigen levels (<10%), the presence of ADAMTS-13 inhibitor or IgG during remission were all significantly associated with a higher hazard of recurrence. CONCLUSIONS: Both the Ig class and subclass are of predictive value for acute episode severity in patients with TTP. Although markers that could predict the risk of recurrence in the acute phase are limited, a thorough assessment of ADAMTS-13-related parameters during remission is warranted. PMID- 22672483 TI - Genetic typing of classical swine fever virus isolates from China. AB - The E2 genes of 73 classical swine fever virus (CSFV) originated from CSF suspected cases in different regions of China were genetically characterized and compared with reference CSF viruses. All Chinese viruses that characterized were segregated into two major groups and subdivided into four subgroups. Most of isolates (61.6%) belonged to group 2 and were further divided into three subgroups: subgroup 2.1, 2.2 and 2.3. Subgroup 2.1 was the largest subgroup which contained 46.6% of isolates, while subgroup 2.3 was the smallest subgroup which contained only one isolate (1.4%). The remaining 38.4% of isolates were classified into subgroup 1.1 within group 1. However, no group 3 and subgroups 1.2 and 1.3 viruses were found in this study. This study has provided epidemiological information useful for assessing the virus origin and establishing a national prevention and control strategy against the disease. PMID- 22672484 TI - Management of venous thromboembolism for older adults in long-term care facilities. AB - PURPOSE: To provide information on current evidence-based clinical management of venous thromboembolism (VTE) for nurse practitioners working for older adults in long-term care facilities. METHODS AND DATA RESOURCES: A systematic review and summary using current clinical guidelines and reliable clinical research studies: American Medical Directors Association, American College of Chest Physicians, Medline, PubMed, Refworks, and CINAHL. CONCLUSIONS: The management of VTE focuses on a comprehensive approach including acute and long-term pharmacologic approach, surgical and mechanical approach, prophylaxis of recurrent VTE, maintaining INR, and monitoring lab values. IMPLICATIONS: Recommendations based on the most current clinical research studies and guidelines will facilitate a cost-effective management of venous thromboembolism for older adults in long-term care facilities. PMID- 22672485 TI - Nonalcoholic fatty liver disease: the hepatic metabolic syndrome. AB - PURPOSE: To examine a case of nonalcoholic fatty liver disease (NAFLD) and review the incidence, pathophysiology, appropriate diagnostic procedures and imaging, clinical considerations, and treatment options. DATA SOURCES: Findings from the history, physical examination, and diagnostic testing of a 39-year-old man with elevated liver enzymes presenting to the hepatology clinic; a search of evidence based literature in the PubMed and CINAHL database with the terms "fatty liver,""nonalcoholic fatty liver disease," and "nonalcoholic steatohepatitis." CONCLUSIONS: NAFLD is the deposition of fat in the liver that can progress to nonalcoholic steatohepatitis, resulting in fibrosis and cirrhosis. The exact pathophysiology is unknown, but risk factors can include those criteria associated with metabolic syndrome. NAFLD is a diagnosis of exclusion and can lead to serious health consequences if it is not identified and interventions are not implemented promptly. Treatment options remain limited but currently focus on weight loss, exercise, and diet. IMPLICATION FOR PRACTICE: The clinician must include the spectrum of NAFLD in the differential diagnosis for any patient with elevated liver enzymes. The key actions for diagnosing NAFLD are identifying risk factors and ordering appropriate testing for confirmation. These considerations will lead to early diagnosis and implementation of treatment interventions. PMID- 22672486 TI - A progressive nurse practitioner student evaluation tool. AB - PURPOSE: To describe the process of designing a new progressive nurse practitioner student clinical evaluation tool based on competencies. DATA SOURCES: Selected research articles and professional organization published guidelines. CONCLUSIONS: Evaluation of nurse practitioner students' clinical performance is an important and often complex responsibility of faculty. The clinical evaluation tool should reflect the changing expectations associated with particular courses across the curriculum and be based on the competencies identified by the National Organization of Nurse Practitioner Faculties. Collaboration by faculty is the key to development of an accurate and useful clinical evaluation tool. IMPLICATIONS FOR PRACTICE: The progressive nurse practitioner clinical evaluation tool presented here is the result of integrating specific clinical course outcomes and competencies recognized by key nurse practitioner associations. PMID- 22672487 TI - Overcoming barriers to practice: A nurse practitioner-led model. AB - PURPOSE: Nurse practitioners (NPs) in Ontario, Canada, experience many barriers to practice that negatively influence their ability to increase access to comprehensive primary healthcare services. A NP-Led Clinic Model has helped to overcome many of the barriers and has had a real impact on access to care. DATA SOURCES: Legislative and regulatory documents from the government of Ontario were reviewed. Reflection upon the barriers to NP practice in Ontario and the positive impact of the new model of care is presented. CONCLUSIONS: NPs with a voice in the governance and operations of a workplace have the potential to reduce barriers to practice. IMPLICATIONS FOR PRACTICE: Lessons for NPs internationally can be learned from the experience of the Ontario NP-Led Clinic Model. PMID- 22672488 TI - Relationships between lifestyle, health behaviors, and health status outcomes for underserved adults. AB - PURPOSE: To examine the relationships between lifestyle, health behaviors, and health status for underserved adults. DATA SOURCES: A convenience sample of 84 adults responded to a questionnaire on lifestyle, health behaviors, health indices, and health status. Health status was measured by the 12-Item Short-Form Health Survey (SF-12). CONCLUSIONS: The majority of the sample was white, female, ranged in age from 19 to 64 years, and had an annual income range of $0-$25,000. Lifestyle factors reported included smoking (44%), consuming alcohol (59%), using street drugs previously (43%), exercising regularly (45%), and having adequate sleep (M= 7.16 h). Sixty-five percent engaged in at least one screening behavior during the past 12 months and used at least one prescription medication. Data for health indices demonstrated subjects had at least one current symptom (89%), at least one current medical condition (72%), and a body mass index classified as overweight (48%). No significant relationships were found between lifestyle and health status. Findings indicated health indices rather than lifestyle were related to health status. IMPLICATIONS FOR PRACTICE: Findings provided selective support for the links between lifestyle, health behaviors, and health status. Nurses can use the results as a basis for future assessments and interventions with underserved adults. PMID- 22672489 TI - Postural balance in young adults: the role of visual, vestibular and somatosensory systems. AB - PURPOSE: The purpose of the study is to examine what sensory system predominates to maintain balance (e.g., visual, vestibular, and somatosensory) among people in their twenties and thirties. DATA SOURCES: A subset of individuals from a larger descriptive cross-sectional study was assessed. A sample of 194 (males = 28%, females = 72%) young adults in the second and third decades of life had anthropometric measurements (height, weight, waist circumference, hip circumference, and leg length) taken and body mass index and waist-to-hip ratio were calculated. Balance was assessed using the NeuroCom Balance Master machine. RESULTS: There was a significant difference among the three sensory systems for postural balance among the young population, F (2, 576) = 111.741, p < .001. Post hoc Bonferroni tests were maintained at the 0.05 level which showed significance for the visual system compared to vestibular and somatosensory system: visual (M = 93.7, SD = 2.07); vestibular (M = 90.4, SD = 2.74); and somatosensory (M = 90.0, SD = 3.13). Based on the results, the visual system is the predominant sensory system used by young adults to maintained optimal postural balance. SIGNIFICANCE FOR PRACTICE: There is very little known about balance of younger adults. If balance issues are identified early in adult life it is possible to prevent exacerbation of balance decline as one age. If nurse practitioners are aware of what dominant sensory systems for balance young adults use, perhaps strategies to preserve these can avoid falls as they age. PMID- 22672490 TI - FRAX(r) counseling for bone health behavior change in women 50 years of age and older. AB - PURPOSE: To evaluate the use of FRAX(r) (Fracture risk assessment tool) for changes in bone health risk factors and treatment decision-making. DATA SOURCES: A convenience sample of seventeen women, 50 years and older, English-speaking, generally healthy, with the ability to perform weight-bearing exercise, presenting for a DXA scan in a Midwestern city between August 2009 and November 2009, and not already being treated for osteoporosis or osteopenia. Self administered diet and exercise questionnaires were completed by participants, followed by individual counseling related to FRAX(r) absolute risk and NOF guidelines. Questionnaires were repeated at approximately three months later, along with a short survey regarding the information's impact. CONCLUSIONS: FRAX(r) increased a participant's perception of future risk for osteoporosis and desire to change bone health habits. About 50% actually made changes in calcium and vitamin D consumption and weight-bearing exercise. FRAX(r) could not be applied to those with osteopenia of the spine only; and a variety of bone health risk factors not covered by FRAX(r) were identified. IMPLICATIONS FOR PRACTICE: The FRAX(r) risk assessment tool can be useful to motivate clients to change bone health behavior. However, it has limitations in its use as a tool for whether or not to prescribe bisphosphonates. PMID- 22672491 TI - Laparoscopic vs open partial nephrectomy for T1 renal tumours: evaluation of long term oncological and functional outcomes in 340 patients. AB - OBJECTIVE: To evaluate the long-term oncological and functional outcomes of laparoscopic partial nephrectomy (LPN) compared with open partial nephrectomy (OPN) for pT1 renal tumours. PATIENTS AND METHODS: In this retrospective single centre study, 340 consecutive patients underwent LPN and OPN for localized, incidentally discovered, renal masses of <7 cm (cT1). The patients were matched for age, sex, body mass index, American Society of Anesthesiology score, tumour side (right or left kidney) and tumour characteristics (RENAL nephrometry score). Demographic data, peri- and postoperative variables, including operating time, estimated blood loss, complications, hospital stay, renal function, histological tumour staging and grading, and metastasis rates were collected and analysed. RESULTS: The median (SEM) operating time for LPN and OPN was 145.3 (45.4) min and 155.2 (35.6) min, respectively (P = 0.07). The median (SEM) warm ischaemia time was 11.7 (2.2) min in the LPN and 14.4 (1.9) min in the OPN group (P = 0.03). The median (SEM) RENAL nephrometry scores for LPN and OPN were 5.9 (1.6) and 6.1 (0.3), respectively (P = 0.11). During follow-up, the biochemical markers of glomerular filtration were completely normalized, showing the absence of renal injury and there was no significant difference in glomerular filtration rate between the groups, with median (SEM) rates of 79.8 (3.0) mL/min/1.72 m(2) for the LPN and 80.2 (2.7) mL/min/1.72 m(2) for the OPN group at 5-year follow-up. The 5-year overall survival and cancer-specific survival rates, calculated using the Kaplan-Meier method, were 94% and 91% in the LPN group, and 92% and 88% in the OPN group. CONCLUSION: LPN and OPN provide similar long-term oncological outcomes in the therapy of T1 renal cancer. With regard to renal function, no damage to the kidney was found after LPN and OPN, with a complete normalization of renal function at the 5-year follow-up in both groups. PMID- 22672492 TI - Severe unilateral vasomotor rhinitis: an antecedent sign of vascular compromise? PMID- 22672493 TI - Common mental disorders in pregnancy in the context of interpartner violence. AB - Pregnancy is generally described as a period with a high incidence of common mental disorders (CMD) in the life cycle of many women who incur the risk of developing mental problems including depression, post-traumatic stress and drug abuse. Our objective with this study was to gauge how the presence of violence in Portuguese pregnant women affected their psychopathology. One hundred and eighty four pregnant outpatients of the Obstetrics and Gynaecology Department of the Hospital Pedro Hispano in Matosinhos, Oporto, Portugal with an average age of 29 and in their last 3 months of pregnancy were the subjects of this study. These participants were divided into two groups: one of abused women (n= 107) and another of non-abused women (n= 77). In order to be able to compare them, both groups were assessed with the Conflict Tactic Scale 2, the Brief Symptom Inventory and the Inventory of the Clinical Evaluation of Depression. It was observed that pregnant women who had suffered violence during pregnancy exhibited some form of CMD during pregnancy. Another important finding was the evidence of the negative impacts that domestic violence had on the mental health of women. PMID- 22672494 TI - All change: the lived experience of younger women with cancer of the vulva. AB - AIMS AND OBJECTIVES: To generate an understanding of the women's own perspectives of their care and address a gap in knowledge in relation to the broader impact of vulval cancer. BACKGROUND: Few people go though life without experiencing events that can change their perspective on how they see themselves, their role in society and their relationship with those around them. People are multi dimensional, so a person with has a physical illness is also affected psychologically and sociologically. DESIGN: Qualitative. METHODS: Based on the work of Heidegger and van Manen, an interpretative phenomenological research study was undertaken to explore the experiences of thirteen women under 50 years of age with vulval cancer living in the UK. RESULTS: Data were analysed using framework analysis and showed that a diagnosis of cancer of the vulva and the subsequent treatment has an effect on physical, psychological and sexual functioning. CONCLUSIONS: The concept of 'All Change' expressed the sentiment that following the diagnosis and surgery, everything has changed; life is not the same as it was before diagnosis. This included both physical and psychological changes and impacts on perceptions of body image. RELEVANCE TO CLINICAL PRACTICE: The challenge is to raise awareness of vulval cancer among health care professions and society in general and determine the most effective interventions in facilitating pre and post operative support for these women. PMID- 22672495 TI - Vitamin D3 receptor is highly expressed in Hodgkin's lymphoma. AB - BACKGROUND: Hodgkin lymphoma (HL) is one of the most frequent lymphoma in the western world. Despite a good overall prognosis, some patients suffer relapsing tumors which are difficult to cure. Over a long period Vitamin D has been shown to be a potential treatment for cancer. Vitamin D acts via the vitamin D receptor, a nuclear receptor, acting as an inducible transcription factor. We aimed to investigate the expression of vitamin D receptor as a possible diagnostic marker and potential therapeutic target in HL as well as in B-cell derived non-Hodgkin lymphoma (B-NHL). METHODS: We used a panel of 193 formalin fixed tissues of lymphoma cases consisting of 55 cases of HL and 138 cases on several B-NHL entities. RESULTS: Vitamin D receptor is strongly expressed in tumor cells of HL, regardless of the sub entity with an overall positivity of 80% of all HL cases. In contrast, only about 17% of the analyzed origin-NHL showed positivity for vitamin D receptor. The detection of nuclear localization of vitamin D receptor in the tumor cells of HL suggests activated status of the vitamin D receptor. CONCLUSIONS: Our study suggests VDR as a specific marker for tumor cells of HL, but not of B-NHL subtypes. Further, the observed nuclear localization suggests an activated receptor status in tumor cells of HL. Further investigations of mutational status and functional studies may shed some light in functional relevance of vitamin D receptor signaling in HL. PMID- 22672496 TI - Can measurement of maternal anti-cytomegalovirus immunoglobulin-M antibody levels be used to screen for cytomegalovirus infection in embryos and fetuses? AB - AIMS: Our study aims to estimate whether measurement of maternal anti cytomegalovirus immunoglobulin-M antibody (CMV-IgM) levels are useful as a screening method for achieving early detection of congenital CMV infection. MATERIAL AND METHODS: Levels of maternal CMV-IgM were measured by enzyme immunoassay in all (n =2865) pregnant women who visited our hospital in the first trimester during the period from January 2005 to December 2009. RESULTS: Among them, 21 individuals (0.73%) had a CMV-IgM titer of >=0.08 and were judged to be CMV-IgM-positive. Informed consent was obtained from all 21 individuals to perform the confirmation test that quantifies the levels of cytomegalovirus DNA (CMV-DNA) in amniotic fluid by real-time polymerase chain reaction. However, only one (0.03%) of the 21 individuals was CMV-DNA-positive (CMV-DNA concentration, 1.0 * 10(4) copies/ml). CONCLUSION: In order to detect congenital CMV infection in early pregnancy, it is considered appropriate to use ultrasound for close examination of embryo or fetal symptoms indicative of CMV instead of performing serological screening based on CMV-IgM. PMID- 22672497 TI - Validity and reliability of a self-reported measure of medication adherence in patients with Type 2 diabetes mellitus in Singapore. AB - AIMS: A reliable and valid measure is essential for the assessment of medication adherence. Until now, no patient-reported medication adherence measure has been validated in Singapore. The aim of this study was to validate a modified 4-item Morisky-Green-Levine Medication Adherence Scale in patients with Type 2 diabetes in Singapore. METHODS: A cross-sectional survey was conducted in a sample of outpatients with Type 2 diabetes in Singapore from September to December in 2009. Respondents completed either an English or Chinese version of the modified 4-item Morisky-Green-Levine Medication Adherence Scale. The scale scores ranged from 0 to 4, with higher scores indicating better medication adherence. Reliability was assessed using Cronbach's alpha. Content validity was assessed by expert review. Construct validity was examined using factor analysis and hypothesis testing. RESULTS: Of the 294 respondents who completed the modified Morisky-Green-Levine Medication Adherence Scale, 13.3, 21.4, 35.7 and 29.6% had a score of 0-1, 2, 3 and 4, respectively. The internal consistency of the scale was moderate (Cronbach's alpha = 0.62). Principal component analysis showed that the four items loaded onto one factor (eigenvalue = 1.95). Respondents with higher scores were older (P < 0.001), had lower HbA(1c) levels (P < 0.001) and had better adherence to physician-recommended diet (P < 0.001) and physical exercise (P = 0.02). CONCLUSIONS: The psychometric properties of the modified Morisky-Green Levine Medication Adherence Scale were less than satisfactory. A ceiling effect was observed. The scale may not be an adequate measure to assess medication adherence in patients with Type 2 diabetes in Singapore. Future research could target refining the scale and investigating its use in other patient populations. PMID- 22672498 TI - Terahertz wave techniques using a metal mesh for evaluating the components of the stratum corneum. AB - BACKGROUND/PURPOSE: Terahertz waves are located in the region of the spectrum between milliwaves and infrared. We analyzed the feasibility of terahertz spectroscopy to inspect the compositional variations of the stratum corneum (SC). METHODS: We used a terahertz time-domain spectroscopy system with the metal mesh technique. To investigate whether terahertz can inspect compositional variation of SC, we measured the terahertz frequency spectra of the SC sheet that was treated with chloroform-methanol, lipid mixture, a denaturation agent, and heating with hot air. RESULTS: The chloroform-methanol treatment of the SC shifted the dip position, which represents a convex downward shape of the spectra, to a higher frequency. This dip shift was reversed to an untreated position by the dose-dependent application of a lipid mixture. The heating treatment of the SC shifted the dip position to a higher frequency. The same dip shift was also induced by the application of a denaturation agent to the SC. CONCLUSION: The technique using terahertz waves with a metal mesh is effective because of its simplicity and its high degree of accuracy in detecting the amount of lipid and the protein conformation state. PMID- 22672499 TI - Small bowel exploration and resection using single-port surgery: a safe and feasible approach. AB - AIM: The aim of this study is to demonstrate the efficacy of wireless capsule endoscopy for preoperative identification of bleeding sources and/or small bowel tumours in surgical patients and to evaluate the feasibility of single-port surgery in the treatment of such pathologies. METHOD: Five patients presenting with obscure gastrointestinal bleeding or/and mild small bowel obstruction were investigated to diagnose and localize the bleeding source or tumour using capsule endoscopy imaging, and, if necessary, with other investigative modalities. All patients were operated on using single-port surgery for small bowel exploration, lesion confirmation, small bowel resection and anastomosis. RESULTS: Small bowel pathology was successfully detected by video capsule endoscopy in three of four patients, and was further substantiated by contrast CT, double-balloon endoscopy or enteroclysis. Complete small bowel exploration, intra-operative identification and oncological resection of the involved segment and anastomosis (intracorporeal and extracorporeal) was successfully performed in all five patients using single port access without any complication, morbidity or mortality. CONCLUSION: This study demonstrates the feasibility and safety of single-port small bowel resection performed after a high-quality preoperative localization of the tumour. PMID- 22672500 TI - Body image of children and adolescents with cancer: a metasynthesis on qualitative research findings. AB - Children and adolescents with cancer are confronted with many challenges. This review considered studies that used qualitative methods to examine the body image experience of children and adolescents with cancer. A systematic literature search of English and Chinese databases was undertaken, covering the period between 1960 and October 2010. Qualitative research findings were extracted and pooled using the Joanna Briggs Institute Qualitative Assessment and Review Instrument. Eight papers met the inclusion criteria. The derived four metasyntheses included being distanced from the body, loss of self-identity, self protective strategies and support, and getting rid of the shackles of the body. In conclusion, children and adolescents with cancer also experience various problems associated with changes in their body image. Repeated courses of treatment lead to loss of a normal, orderly life, and might even result in changes in interpersonal interactions. In response to body image change, individuals with cancer develop self-protective, coping strategies. Children and adolescents who experience life-threatening cancer come to face body image change positively, and might hold a confident attitude toward their future. PMID- 22672501 TI - Effects of a vildagliptin/metformin combination on markers of atherosclerosis, thrombosis, and inflammation in diabetic patients with coronary artery disease. AB - BACKGROUND: Diabetic patients present with an accelerated atherosclerotic process and an increased risk for future cardiovascular events. In addition to the risk imposed by the disease itself, pharmacological treatment adds also a sizable risk, especially if certain classes of antidiabetic drugs are employed. Animal evidence indicates that dipeptidyl peptidase-4 inhibitors have anti atherosclerotic effects, yet clinical data are scarcely available. DESIGN: We plan to prospectively investigate the effects of dipeptidyl peptidase-4 inhibition with vildagliptin on a number of atherothrombotic markers and adipokines in patients with proven atherosclerosis and type 2 diabetes. The selected markers are: interleukin-6, high sensitivity C reactive protein, interleukin 1-beta, total adiponectin levels, matrix metallo-proteinase 9 and platelet reactivity testing. Sixty eligible patients will be randomized in a 2:1 ratio to vildagliptin/metformin or metformin only treatment, for a 3-month duration treatment. Blood sampling for the proposed investigations will be taken at enrollment and immediately after completion of the study period. DISCUSSION: Demonstrating antiatherothrombotic properties of dipeptidyl peptidase-4 inhibitors on proven markers is of substantial clinical significance. Coupled with their proven good safety profile these findings could translate into a significant clinical benefit. PMID- 22672502 TI - Borderline personality features and development of psychosis in an 'ultra high risk' (UHR) population: a case control study. AB - AIMS: There is clinical uncertainty as to whether borderline personality disorder (BPD) traits in those with an 'at risk mental state' have an effect on the risk of 'transition' to psychosis. We aimed to investigate the relationship between baseline BPD features, risk of transition and type of psychotic disorder experienced. METHOD: This is a case-control study of 'ultra high risk' (UHR) for psychosis patients treated at the clinic, between 2004 and 2007. 'Cases' were UHR individuals who made the 'transition' to full threshold psychotic disorder within 24 months; 'control' group was a matched UHR sample who had not developed a psychotic disorder at 24 months. Individuals were matched on time of entry to the clinic, age and gender. Diagnostic and statistical manual of mental disorders, fourth edition (DSM-IV) BPD features were assessed from clinical assessments using a structured instrument (Structured Clinical Interview for DSM-IV Axis II Disorder for BPD (SCID-II BPD)). Psychosis diagnosis following transition was rated from the clinical files using the operational criteria in studies of psychotic illness (OPCRIT) computer algorithm. The number of BPD traits and number with full threshold BPD were compared in those who developed psychosis and those who did not. RESULTS: We analysed data from 48 cases and 48 controls. There was no statistically significant difference in the rate of transition to psychosis for those with baseline full-threshold BPD, compared with those without BPD. The number of BPD traits or number with full threshold BPD did not differ by psychosis diagnosis grouping. CONCLUSIONS: Co-occurring BPD or BPD features does not appear to strongly influence the risk of short-term transition to psychosis or the risk of developing a non-affective psychotic disorder in this population. PMID- 22672503 TI - Interaction between dopamine- and isotocin-containing neurones in the preoptic area of the catfish, Clarias batrachus: role in the regulation of luteinising hormone cells. AB - Apart from gonadotrophin-releasing hormone (GnRH) and dopamine (DA), oxytocin has emerged as an important endogenous agent that regulates reproduction. Although the interaction between these factors has been extensively studied in mammals, parallel information in teleosts is much limited. We studied the organisation of tyrosine hydroxylase (TH; a marker for dopamine) and isotocin neurones in the preoptic area (POA) and hypothalamus of the catfish, Clarias batrachus and its implication in the regulation of luteinising hormone (LH) cells in the pituitary. Nucleus preopticus periventricularis (NPP), a major dopaminergic centre in the brain, consists of anterior (NPPa) and posterior (NPPp) subdivisions. Using retrograde neuronal tracing, we found that majority of the DA neurones in NPPa, but none from NPPp, project to the pituitary. The nucleus preopticus (NPO) of C. batrachus contains a conspicuous assemblage of large isotocin-positive neurones. It consists of a paraventricular subdivision (NPOpv) located on either side of the third ventricle and lies roughly sandwiched between the dopaminergic neurones of NPPa and NPPp. An additional subset of isotocin neurones was located above the optic chiasm in the supraoptic subdivision of the NPO (NPOso). Isotocin containing neurones in both the subdivisions of NPO were densely innervated by DA fibres. Superfusion of the POA-containing brain slices with DA D(1) -like receptor agonist (SKF-38393) resulted in significant increase in isotocin immunoreactivity in the NPOpv neurones; NPOso neurones did not respond. However, treatment with DA D(2) -like receptor agonist (quinpirole) reduced isotocin immunoreactivity in the NPOso, but not in the NPOpv. Thus, DA appears to differentially regulate the components of isotocinergic system. Isotocin fibres extend to the pituitary and terminate on LH cells and the superfused pituitary slices treated with isotocin caused significant reduction in LHbeta immunoreactivity. An elaborate interplay between the DA and isotocin systems appears to be an important component of the LH regulatory system. PMID- 22672504 TI - Antimicrobial susceptibility testing of Clostridium difficile using EUCAST epidemiological cut-off values and disk diffusion correlates. AB - With the emergence of reduced susceptibility of Clostridium difficile to metronidazole and vancomycin the value of antimicrobial susceptibility testing has increased. The aim of our study was to evaluate disk diffusion for susceptibility testing of C. difficile by comparing disk diffusion results with MICs from gradient tests and to propose zone diameter breakpoint correlates for the EUCAST epidemiological cut-off values (ECOFFs) recently published. We tested 211 clinical isolates of C. difficile, from patients with diarrhoea hospitalized at Aarhus and Odense University Hospitals, Denmark. Furthermore, ten clinical isolates of C. difficile from the Anaerobe Reference Laboratory, University Hospital of Wales, with known reduced susceptibility to either metronidazole or vancomycin, were included. Isolates were tested with Etest gradient strips and disk diffusion towards metronidazole, vancomycin and moxifloxacin on Brucella Blood Agar supplemented with hemin and vitamin K. We found an excellent agreement between inhibition zone diameter and MICs. For each MIC value, the inhibition zones varied from 0 to 8 mm, with 93% of values within 6 mm for metronidazole, 95% of values within 4 mm for vancomycin, and 98% of values within 4 mm for moxifloxacin. With proposed zone diameter breakpoints for metronidazole, vancomycin and moxifloxacin of WT >= 23 mm, WT >= 19 and WT >= 20 mm, respectively, we found no very major errors and only major errors below 2%. In conclusion, we suggest that disk diffusion is an option for antimicrobial susceptibility testing of C. difficile. PMID- 22672505 TI - Normal and cancer cell metabolism: lymphocytes and lymphoma. AB - Recent studies of normal and neoplastic lymphocytes have revealed overlapping metabolic rewiring in activated T cells and Myc-transformed lymphocytes. Myc expression is attenuated in normal lymphocytes that return to the basal state, but Notch-activated or Myc-transformed lymphocytes persistently express Myc, which activates genes involved in glucose and glutamine metabolism. Although this difference could provide a therapeutic window for the treatment of cancers, the overlapping metabolic profiles suggest a potential for immunosuppression by metabolic inhibitors. PMID- 22672507 TI - Nanoparticle loading level and properties of experimental hybrid resin luting agents. AB - PURPOSE: This study investigated the influence of nanoparticle loading level on properties of experimental hybrid resin luting agents. MATERIALS AND METHODS: Silanated 2-MUm barium borosilicate glass microparticles and 7-nm silica nanoparticles were used. Five materials were obtained by loading a photocurable Bis-GMA/TEGDMA co-monomer with a total mass fraction of 60% inorganic fillers. The mass fraction of nanoparticles was set at 0% (control), 1% (G1), 2.5% (G2.5), 5% (G5), or 10% (G10). The properties evaluated were flexural strength (sigma) and modulus (E(f) ), Knoop hardness number (KHN), and film thickness (FT). Dispersion/interaction of the particles with the resin phase was assessed by scanning electron microscopy (SEM). Data were submitted to statistical analysis (5%). RESULTS: For sigma, G1 > G2.5 = G5 = G10, and control > G10. For E(f) , G2.5 > control = G1 > G5 > G10. For KHN, G5 = G10 > control = G1 = G2.5. For FT, G10 = G5 > control = G1, and G10 > G2.5. Incorporation of nanoparticles was associated with observation of clusters in the SEM analysis. The clusters were more frequent for higher nanoparticle loadings. CONCLUSION: Modest incorporation of nanoparticles may improve the properties of resin luting materials. Nanofiller mass fractions above 2.5% should, however, be avoided because they may be detrimental to the properties of the resin luting agents. PMID- 22672508 TI - Apparent zinc absorption and zinc status of weanling rats fed moderately zinc deficient diets enriched with beef tallow or sunflower oil. AB - The aim of the study was to compare apparent Zn absorption and Zn status of weanling rats fed diets that differed in Zn level, fat level and fat source. Semi synthetic diets, which were about isoenergetic and contained 3% soyabean oil, were supplemented with 7 or 100 mg Zn/kg to create a mild Zn deficiency (LZ) or a high Zn supply (HZ) and with 0 (LF), 22% beef tallow (BT) or 22% sunflower oil (SF) according to a 2 * 3 factorial design of treatments. They were fed ad libitum to 6 * 8 rats for 28 days. Energy intake and growth rates were comparable among the HZ groups. Weight gains in the LZ-LF, LZ-BT and LZ-SF groups averaged 5.54, 4.95 and 4.15 g/day, and apparent Zn absorption averaged 79.4, 60.3 and 48.0 MUg Zn/day, respectively, whereas faecal Zn excretion was comparable among these groups. Apparent Zn absorption, and plasma and femur Zn concentrations were lower in the high-fat groups than in the LF group, possibly due to the high cellulose content of the BT and SF diets. Plasma Zn concentrations were higher in the animals fed the BT-based than in the SF-based diets, whereas femur and soft tissue Zn concentrations were comparable among these groups. The differences between the LZ-BT and LZ-SF groups in growth rate, Zn absorption rate and Zn status were confirmed in a second experiment. The results indicate that moderately Zn-deficient diets enriched with SF in relation to BT affect Zn metabolism of weanling rats by a yet unknown mechanism. PMID- 22672506 TI - The type III secretion system is necessary for the development of a pathogenic and endophytic interaction between Herbaspirillum rubrisubalbicans and Poaceae. AB - BACKGROUND: Herbaspirillum rubrisubalbicans was first identified as a bacterial plant pathogen, causing the mottled stripe disease in sugarcane. H. rubrisubalbicans can also associate with various plants of economic interest in a non pathogenic manner. RESULTS: A 21 kb DNA region of the H. rubrisubalbicans genome contains a cluster of 26 hrp/hrc genes encoding for the type three secretion system (T3SS) proteins. To investigate the contribution of T3SS to the plant-bacterial interaction process we generated mutant strains of H. rubrisubalbicans M1 carrying a Tn5 insertion in both the hrcN and hrpE genes. H. rubrisulbalbicans hrpE and hrcN mutant strains of the T3SS system failed to cause the mottled stripe disease in the sugarcane susceptible variety B-4362. These mutant strains also did not produce lesions on Vigna unguiculata leaves. Oryza sativa and Zea mays colonization experiments showed that mutations in hrpE and hrcN genes reduced the capacity of H. rubrisulbalbicans to colonize these plants, suggesting that hrpE and hrcN genes are involved in the endophytic colonization. CONCLUSIONS: Our results indicate that the T3SS of H. rubrisubalbicans is necessary for the development of the mottled stripe disease and endophytic colonization of rice. PMID- 22672509 TI - A primary left atrial leiomyosarcoma mimicking myxoma: echocardiographic findings. AB - Echocardiography is the initial imaging modality to delineate the cardiac mass. Clinically echocardiographic information about morphology, location, motion and hemodynamic consequences of the tumor is very important for decision making in terms of additional imaging studies and treatment. We present a case of left atrial leiomyosarcoma masquerading as myxoma preoperatively and discuss the echocardiographic features for distinguishing leiomyosarcoma from a benign tumor, such as myxoma. PMID- 22672510 TI - Burden of disease resulting from chronic mountain sickness among young Chinese male immigrants in Tibet. AB - BACKGROUND: In young Chinese men of the highland immigrant population, chronic mountain sickness (CMS) is a major public health problem. The aim of this study was to measure the disease burden of CMS in this population. METHODS: We used disability-adjusted life years (DALYs) to estimate the disease burden of CMS. Disability weights were derived using the person trade-off methodology. CMS diagnoses, symptom severity, and individual characteristics were obtained from surveys collected in Tibet in 2009 and 2010. The DALYs of individual patients and the DALYs/1,000 were calculated. RESULTS: Disability weights were obtained for 21 CMS health stages. The results of the analyses of the two surveys were consistent with each other. At different altitudes, the CMS rates ranged from 2.1-37.4%; the individual DALYs of patients ranged from 0.13-0.33, and the DALYs/1,000 ranged from 3.60-52.78. The age, highland service years, blood pressure, heart rate, smoking rate, and proportion of the sample working in engineering or construction were significantly higher in the CMS group than in the non-CMS group (p < 0.05). These variables were also positively associated with the individual DALYs (p < 0.05). Among the symptoms, headaches caused the largest proportion of DALYs. CONCLUSION: The results show that CMS imposes a considerable burden on Chinese immigrants to Tibet. Immigrants with characteristics such as a higher residential altitude, more advanced age, longer highland service years, being a smoker, and working in engineering or construction were more likely to develop CMS and to increase the disease burden. Higher blood pressure and heart rate as a result of CMS were also positively associated with the disease burden. The authorities should pay attention to the highland disease burden and support the development and application of DALYs studies of CMS and other highland diseases. PMID- 22672511 TI - Antimicrobial susceptibilities and resistance genes in Campylobacter strains isolated from poultry and pigs in Australia. AB - AIMS: To evaluate the phenotypic and genotypic profiles of Campylobacter spp. from poultry faecal samples from free range or intensively raised meat chickens and free range egg layers. In addition, a case-comparison study of antibiotic resistance genes from different groups of poultry and some pig strains previously collected was carried out. METHODS: Resistance to different antibiotics was assessed using the agar dilution method. In addition, all the strains were tested for ampicillin (bla(OXA-61) ), erythromycin (aph-3-1), tetracycline tet(O), streptomycin (aadE), and the energy-dependent multi-drug efflux pump (cmeB) resistance genes using multiplex polymerase chain reaction. RESULTS: The evaluation of phenotypic resistance revealed all of the strains from poultry were sensitive to ciprofloxacin, gentamicin, erythromycin or tylosin. But, widespread resistance to lincomycin (51-100%), extensive resistance to ampicillin (33.3 60.2%) and less resistance to tetracycline (5.6-40.7%) were observed in the different groups of chickens. Antibiotic resistance genes bla(OXA-61,) cmeB and tet(O) were found in 82.6-92.7%, 80.3-89% and 22.3-30.9% Camp. coli isolates from pigs, whilst 59-65.4% and 19.2-40.7% Camp. jejuni from chickens were found to encode bla(OXA-61) and tet(O), respectively. CONCLUSION: No significant difference between isolates from free range egg layers and meat chickens (P < 0.05) was found. However, there were significant differences between the pig strains and all the groups of poultry strains (P < 0.05) with regard to carriage of resistance genes. In addition, pulsed field gel electrophoresis of selected resistant isolates from the poultry and pig revealed closely related clonal groups. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results suggest the resistant strains are persisting environmental isolates that have been acquired by the different livestock species. Furthermore, the different treatment practices in poultry and pigs have resulted in differences in resistance profiles in Campylobacter isolates. PMID- 22672513 TI - Template stamps to estimate recipient site density in hair transplantation. PMID- 22672512 TI - Patterns of functional enzyme activity in fungus farming ambrosia beetles. AB - INTRODUCTION: In wood-dwelling fungus-farming weevils, the so-called ambrosia beetles (Curculionidae: Scolytinae and Platypodinae), wood in the excavated tunnels is used as a medium for cultivating fungi by the combined action of digging larvae (which create more space for the fungi to grow) and of adults sowing and pruning the fungus. The beetles are obligately dependent on the fungus that provides essential vitamins, amino acids and sterols. However, to what extent microbial enzymes support fungus farming in ambrosia beetles is unknown. Here we measure (i) 13 plant cell-wall degrading enzymes in the fungus garden microbial consortium of the ambrosia beetle Xyleborinus saxesenii, including its primary fungal symbionts, in three compartments of laboratory maintained nests, at different time points after gallery foundation and (ii) four specific enzymes that may be either insect or microbially derived in X. saxesenii adult and larval individuals. RESULTS: We discovered that the activity of cellulases in ambrosia fungus gardens is relatively small compared to the activities of other cellulolytic enzymes. Enzyme activity in all compartments of the garden was mainly directed towards hemicellulose carbohydrates such as xylan, glucomannan and callose. Hemicellulolytic enzyme activity within the brood chamber increased with gallery age, whereas irrespective of the age of the gallery, the highest overall enzyme activity were detected in the gallery dump material expelled by the beetles. Interestingly endo-beta-1,3(4)-glucanase activity capable of callose degradation was identified in whole-body extracts of both larvae and adult X. saxesenii, whereas endo-beta-1,4-xylanase activity was exclusively detected in larvae. CONCLUSION: Similar to closely related fungi associated with bark beetles in phloem, the microbial symbionts of ambrosia beetles hardly degrade cellulose. Instead, their enzyme activity is directed mainly towards comparatively more easily accessible hemicellulose components of the ray-parenchyma cells in the wood xylem. Furthermore, the detection of xylanolytic enzymes exclusively in larvae (which feed on fungus colonized wood) and not in adults (which feed only on fungi) indicates that only larvae (pre-) digest plant cell wall structures. This implies that in X. saxesenii and likely also in many other ambrosia beetles, adults and larvae do not compete for the same food within their nests - in contrast, larvae increase colony fitness by facilitating enzymatic wood degradation and fungus cultivation. PMID- 22672514 TI - Nomogram and scoring system for predicting stone-free status after extracorporeal shock wave lithotripsy in children with urolithiasis. AB - OBJECTIVE: To determine the stone-free rate after extracorporeal shock wave lithotripsy (ESWL) and its associated factors to formulate a nomogram table and scoring system to predict the probability of stone-free status in children. PATIENTS AND METHODS: A total of 412 children (427 renal units [RUs]) with urolithiasis were treated with ESWL using a lithotriptor between 1992 and 2008. Cox proportional hazards regression was used to model the number of treatment sessions to stone-free status as a function of statistically significant demographic characteristics, stones and treatment variables. A bootstrap method was used to evaluate the model's performance. Based on the multivariate model, the probabilities of being stone-free after each treatment session (1, 2 and >3) were then determined. A scoring system was created from the final multivariate proportional hazard model to evaluate each patient and predict their stone-free probabilities. RESULTS: Complete data were available for 395 RUs in 381 patients. Of the 395 RUs, 303 (76.7%) were considered to be stone-free after ESWL. Multivariate analysis showed that previous history of ipsilateral stone treatment is related to stone-free status (hazard ratio [HR]: 1.49; P = 0.03). Stone location was a significant variable for stone-free status, but only in girls. Age (HR 1.65, P = 0.02) and stone burden (HR 4.45, P = 0.002) were significant factors in the multivariate model. CONCLUSION: We believe that the scoring system, and nomogram table generated, will be useful for clinicians in counselling the parents of children with urolithiasis and in recommending treatment. PMID- 22672515 TI - Kidney transplant ureteroneocystostomy: comparison of full-thickness vs. Lich Gregoir techniques. AB - Despite a variety of urinary tract reconstructive techniques, urinary complications are the most frequent technical adverse event following kidney transplantation. We examined outcomes of two ureteroneocystostomy techniques, the full-thickness (FT) technique and the Lich-Gregoir (LG) technique in 634 consecutive kidney-alone transplants (327 FT and 307 LG) between December 2006 and December 2010. Urological complications at one yr post-transplantation occurred in 27 cases (4.3%) including 16 ureteral strictures (2.5%), four ureteral obstructions (0.6%) owing to donor-derived stones or intrinsic hematoma, and seven urine leaks (1.1%). Compared with LG, the FT technique was associated with similar proportions of ureteral complications overall (3.9% vs. 4.6%, p = 0.70), ureteral strictures (3.7% vs. 1.3%, p = 0.08), urinary stones/hematoma (1.0% vs. 0.3%, p = 0.36), and overall urinary leaks (1.6% vs. 0.6%, p = 0.22); however, the FT technique was associated with somewhat fewer urine leaks at the ureterovesical junction (0% vs. 1.3%, p = 0.05). There were no differences between the two groups in terms of length of stay, delayed graft function, urinary tract infection with the first post-transplant year, estimated glomerular filtration rate, and overall graft and patient survival. The FT technique of ureteroneocystostomy is technically simple to perform and has a similar incidence of urinary complications compared with the LG technique. PMID- 22672516 TI - Review of penile prosthetic reservoir: complications and presentation of a modified reservoir placement technique. AB - INTRODUCTION: Multiple modifications have been made to the inflatable penile prosthesis (IPP) since its inception in the 1970s. These modifications have made reservoir-related mechanical malfunctions highly unlikely in current IPP models. Although these complications are rare, it would be incumbent upon the implanting surgeon to be aware of these potential complications, how they present, how they are best treated, and how to prevent them from occurring. AIMS: The aim of this article was to present our experience with complications associated with penile prosthesis reservoirs, perform a review of the literature regarding reservoir related complications, and present our modified technique to place the reservoir into the space of Retzius. MAIN OUTCOME MEASURES: Reservoir-related complications including inguinal herniation, erosion into bladder or bowel, intraperitoneal reservoir placement with subsequent visceral injury, vascular injury, autoinflation, and infection. METHODS: We retrospectively reviewed our experience with penile prosthesis reservoir complications or procedures requiring an alternative implantation approach at our center over the past 10 years where over 400 devices were implanted. We also review reservoir-related complications published in the English literature since the 1980s. RESULTS: While exceedingly rare, reservoir complications do occur. Six cases from our institution are presented including one reservoir herniation, one postoperative direct inguinal hernia, one bladder laceration during revision surgery, one ectopic reservoir placement due to morbid obesity, one iliac vein compression syndrome, and one vascular laceration during reservoir revision. Reported reservoir complications include inguinal herniation, erosion into the bladder or bowel, intraperitoneal reservoir placement with subsequent injury to the ureter or bowel, vascular injury, autoinflation, and infection. CONCLUSION: Penile prosthesis reservoirs rarely fail mechanically but are associated with a variety of complications or may require alternate implantation technique. In our experience, the Jorgensen scissors technique allows safe entry into the space of Retzius with diminished risk of hernia as well as vascular, bladder, or bowel injury. PMID- 22672517 TI - The adapter protein ADAP is required for selected dendritic cell functions. AB - BACKGROUND: The cytosolic adaptor protein ADAP (adhesion and degranulation promoting adapter protein) is expressed by T cells, natural killer cells, myeloid cells and platelets. ADAP is involved in T-cell-receptor-mediated inside-out signaling, which leads to integrin activation, adhesion and reorganization of the actin cytoskeleton. However, little is known about the role of ADAP in myeloid cells. In the present study, we analyzed the function of ADAP in bone-marrow derived dendritic cells (BMDCs) from ADAP-deficient mice. RESULTS: ADAP-deficient BMDCs showed almost normal levels of antigen uptake, adhesion, maturation, migration from the periphery to the draining lymph nodes, antigen-specific T-cell activation, and production of the proinflammatory cytokines IL-6 and TNF-?. Furthermore, we provide evidence that the activation of signaling pathways after lipopolysaccharide (LPS) stimulation are not affected by the loss of ADAP. In contrast, ADAP-deficient BMDCs showed defects in CD11c-mediated cellular responses, with significantly diminished production of IL-6, TNF-? and IL-10. Actin polymerization was enhanced after CD11c integrin stimulation. CONCLUSIONS: In summary, we propose that the adapter molecule ADAP is critical for selected CD11c integrin-mediated functions of dendritic cells. PMID- 22672518 TI - Tuning multiple motor travel via single motor velocity. AB - Microtubule-based molecular motors often work in small groups to transport cargos in cells. A key question in understanding transport (and its regulation in vivo) is to identify the sensitivity of multiple-motor-based motion to various single molecule properties. Whereas both single-motor travel distance and microtubule binding rate have been demonstrated to contribute to cargo travel, the role of single-motor velocity is yet to be explored. Here, we recast a previous theoretical study, and make explicit a potential contribution of velocity to cargo travel. We test this possibility experimentally, and demonstrate a strong negative correlation between single-motor velocity and cargo travel for transport driven by two motors. Our study thus discovers a previously unappreciated role of single-motor velocity in regulating multiple-motor transport. PMID- 22672519 TI - Proinflammatory effects of cookstove emissions on human bronchial epithelial cells. AB - Approximately half of the world's population uses biomass fuel for indoor cooking and heating. This form of combustion typically occurs in open fires or primitive stoves. Human exposure to emissions from indoor biomass combustion is a global health concern, causing an estimated 1.5 million premature deaths each year. Many 'improved' stoves have been developed to address this concern; however, studies that examine exposure-response with cleaner-burning, more efficient stoves are few. The objective of this research was to evaluate the effects of traditional and cleaner-burning stove emissions on an established model of the bronchial epithelium. We exposed well-differentiated, normal human bronchial epithelial cells to emissions from a single biomass combustion event using either a traditional three-stone fire or one of two energy-efficient stoves. Air-liquid interface cultures were exposed using a novel, aerosol-to-cell deposition system. Cellular expression of a panel of three pro-inflammatory markers was evaluated at 1 and 24 h following exposure. Cells exposed to emissions from the cleaner burning stoves generated significantly fewer amounts of pro-inflammatory markers than cells exposed to emissions from a traditional three-stone fire. Particulate matter emissions from each cookstove were substantially different, with the three stone fire producing the largest concentrations of particles (by both number and mass). This study supports emerging evidence that more efficient cookstoves have the potential to reduce respiratory inflammation in settings where solid fuel combustion is used to meet basic domestic needs. PRACTICAL IMPLICATIONS: Emissions from more efficient, cleaner-burning cookstoves produced less inflammation in well-differentiated bronchial lung cells. The results support evidence that more efficient cookstoves can reduce the health burden associated with exposure to indoor pollution from the combustion of biomass. PMID- 22672520 TI - Denying the effects of psychiatric drugs on health is indeed a scandal. PMID- 22672521 TI - Left ventricular diastolic dysfunction in atrial fibrillation: predictors and relation with symptom severity. AB - BACKGROUND: Left ventricular diastolic dysfunction (LVDD) is common in the general population, but its prevalence in atrial fibrillation (AF), predictors for LVDD in AF and the association between LVDD and AF-related symptom severity has not been well studied. METHODS: In 124 consecutive patients (mean age 61 +/- 11years, 60% male) with paroxysmal (n = 70) or persistent AF (n = 54) referred for AF catheter ablation, LVDD was evaluated according to current guidelines using transthoracic echocardiography. AF-related symptom severity was quantified using the European Heart Rhythm Association score. RESULTS: LVDD was present in 46 patients (37%). In uni- and multivariable regression analysis, age (OR 1.068 per year, 95% CI 1.023-1.115, P = 0.003) and persistent AF (OR 2.427 vs. paroxysmal AF, 95% CI 1.112-5.3, P = 0.026) were associated with LVDD. LVDD was found in 11% with mild AF symptoms (n = 27) as opposed to 44% in patients with moderate-severe AF symptoms (n = 97, P = 0.002). Thus, the OR for moderate-severe AF symptoms was 6.368 (1.797-22.568, P = 0.004) in the presence of LVDD. CONCLUSIONS: LVDD (1) occurs frequently in AF, (2) is associated with advancing age and AF progression and (3) is correlated with symptom severity in AF. PMID- 22672522 TI - Identification of a third rearrangement at Xq28 that causes severe hemophilia A as a result of homologous recombination between inverted repeats. AB - BACKGROUND: Intrachromosomal homologous recombination between inverted repeats on the X chromosome account for about half of severe hemophilia A cases. Repeats in F8 intron 1 and intron 22 can recombine with homologous inverted repeats located about 200 kb upstream and 500 kb downstream of F8, respectively, resulting in partial sequence inversion of the F8 open reading frame and, subsequently, no functional protein production. OBJECTIVES: In the present study, we characterize a third novel homologous recombination at Xq28 consistent with absence of F8 transcription that we previously reported for the affected chromosome of the index patient as well as his mother and sister. RESULTS: The rearrangement occurs between a repeat in F8 intron 1 (Int1R-1) and an inverted identical repeat (Int1R 2d) in intron 2 of a duplicated copy of IKBKG located about 386 kb upstream of F8. The rearrangement was confirmed by Southern blot and inverse PCR and results in failure of PCR amplification across Int1R-1. CONCLUSION: We developed a PCR based diagnostic method that can be used to screen for this genetic rearrangement in cases of severe hemophilia A for which mutations cannot be identified. PMID- 22672523 TI - Prevention of post-stroke cognitive decline: a review focusing on lifestyle interventions. AB - BACKGROUND AND PURPOSE: Despite a high prevalence of post-stroke cognitive impairment, therapeutic possibilities are still limited. Stroke and dementia share the same cluster of modifiable risk factors. Thus, lifestyle interventions and strict adherence to medication may not only decrease the risk of recurrent stroke but also the risk of post-stroke cognitive decline. METHODS: We performed a systematic literature search for randomized clinical trials (RCTs) targeting modifiable risk factors for the prevention of cognitive decline following stroke. RESULTS: We identified 25 non-pharmacological interventions and eight multiple risk factor interventions in stroke patients using cognition as outcome measure. None of the published trials investigated interventions aimed at the prevention of post-stroke cognitive decline. However, a number of ongoing trials aim at risk factor reduction and include measures on cognition. CONCLUSION: Evidence for risk factor modification for the prevention of cognitive decline after stroke is scarce and comes mainly from observational studies. There is a need for more RCTs targeting the prevention of post-stroke dementia using lifestyle interventions and a multiple risk factor approach. PMID- 22672525 TI - Detection of Brucella spp. DNA in the semen of seronegative bulls by polymerase chain reaction. AB - Semen samples from 88 reproductively mature bulls were screened to detect the presence of Brucella spp. by polymerase chain reaction. Twenty-seven samples were found to be positive, underscoring the importance of researching brucellosis in males and the need for greater care in the selection of sperm-donating bulls for semen centres. PMID- 22672524 TI - Biological characterization and selection criteria of adjuvant chemotherapy for early breast cancer: experience from the Italian observational NEMESI study. AB - BACKGROUND: International treatment guidelines recommend administration of adjuvant chemotherapy in early breast cancer based on clinical, prognostic and predictive parameters. METHODS: An observational study (NEMESI) was conducted in 63 Italian oncology centres in patients with early breast cancer. Age, performance status, concomitant disease, menopausal status, histology, tumor dimension (pT), axillary lymph node status (pN), grading (G), estrogen and progesterone receptor (ER and PgR), proliferative index (ki67 or MIB-1), human epidermal growth factor receptor 2 (HER2) and type of adjuvant treatment were recorded. The primary objective of the study was to define parameters influencing the decision to prescribe adjuvant chemotherapy and the type of chemotherapy. RESULTS: Data for 1894 patients were available. 69.0% postmenopausal, 67.0% pT1, 22.3% pTmic/pT1a/pT1b, 61.0% pN0, 48.7% luminal A, 18.1% luminal B, 16.1% HER2 positive, 8.7% triple negative, 8.4% unknown. 57.8% received adjuvant chemotherapy: 38.1% of luminal A, 67.3% luminal B, 88.2% HER2-positive, 97.6% triple negative. Regimens administered: 9.1% CMF-like, 48.8% anthracyclines, 38.4% anthracyclines plus taxanes, 3.7% taxanes alone. Increasing pT/pN and, marginally, HER2-positive were associated with the prescription of anthracyclines plus taxanes. Suboptimal schedules (CMF-like or AC/EC or FEC-75) were prescribed in 37.3% receiving chemotherapy, even in HER2-positive and triple negative disease (36.5% and 34.0%, respectively). CONCLUSIONS: This study showed an overprescription of adjuvant chemotherapy for early breast cancer, particularly referred to luminal A. pT, pN and, marginally, HER2 were the principal determinants for the choice of chemotherapy type. Suboptimal chemotherapy regimens were adopted in at least one third of HER2-positive and triple negative. PMID- 22672526 TI - An ethnographic study of main events during hospitalisation: perceptions of nurses and patients. AB - AIM: To explore nurses' and patients' perceptions of care during main events of hospitalisation. BACKGROUND: Main events during hospitalisation such as admission, transfer to the operation room and preparation for discharge have been identified as times when there is significant patient-caregiver interaction. It is during these interactions that there is an opportunity for the nurse to have a positive influence on the patient's satisfaction with care. The patient's perception of care has been studied but not qualitatively. Perceptions of care from the nurses' perspectives have not been well studied. This study explored the patient's perception of care as well as the nurse's perception of the care he provided. DESIGN: This study used an ethnographic methodology that included participant observation and unstructured interviews. METHOD: The research was conducted in two phases. First, participant observation was chosen to observe and understand nurse-patient and nurse-family behaviour. The second phase was an unstructured interview to elicit both the patient's and the nurse's views about the care experience. RESULTS: Two major findings were the patient and the nurse had different perceptions of the care experience and the presence of family or a support person influenced the patient's perception of care. CONCLUSION: The use of ethnography proved to be a valuable methodology for studying the interactions of patients, families and nurses. Qualitative methods such as ethnography can yield significant findings on perceptions that are unable to be gleaned by traditional quantitative methods but can serve to provide hypotheses for further study. Relevance to clinical practice. This study suggests that to maintain quality and patient satisfaction scores, hospitals will need to focus on the difference between the perceived care given and the perceived care received particularly during main events. The role of families and visitors supports positive perceptions of care. PMID- 22672527 TI - Borderline mucinous ovarian tumor presenting as pseudo-Meigs' syndrome. AB - Borderline ovarian tumor with the initial presentation of pseudo-Meigs' syndrome is rare. A 52-year-old postmenopausal woman presented with a large ovarian tumor, ascites, and right hydrothorax. We found elevated serum carcinoembryonic antigens (44.4 ng/mL), carbohydrate antigen (CA)-125 (269.8 U/mL), and CA-199 (7942 U/mL). The frozen section pathology revealed a mucinous borderline ovarian tumor, and a staging operation was performed. Final pathologic examination confirmed the diagnosis of intestinal type ovarian mucinous borderline tumor with non-invasive cul-de-sac implants. Her pleural effusion and ascites resolved after surgery, and she remained tumor-free after 3 years' follow up. Physicians should be cautious for the rare possibility of pseudo-Meigs' syndrome in patients with pelvic tumors having the features of advanced ovarian cancer. PMID- 22672528 TI - TRAIL and vitamins: opting for keys to castle of cancer proteome instead of open sesame. AB - Cancer is a multifaceted molecular disorder that is modulated by a combination of genetic, metabolic and signal transduction aberrations, which severely impair the normal homeostasis of cell growth and death. Accumulating findings highlight the fact that different genetic alterations, such as mutations in tumor suppressor genes, might be related to distinct and differential sensitivity to targeted therapies. It is becoming increasingly apparent that a multipronged approach that addresses genetic milieu (alterations in upstream and/or parallel pathways) eventually determines the response of individual tumors to therapy. Cancerous cells often acquire the ability to evade death by attenuating cell death pathways that normally function to eliminate damaged and harmful cells. Therefore impaired cell death nanomachinery and withdrawal of death receptors from cell surface are some of major determinants for the development of chemotherapeutic resistance encountered during treatment. It is therefore essential to emphasize underlying factors which predispose cells to refractoriness against TRAIL mediated cell death pathway and the relevant regulatory components involved. We bring to limelight the strategies to re sensitize TRAIL resistant cells via vitamins to induce apoptosis. PMID- 22672529 TI - A fatal neuromuscular disease in an adult patient after poliomyelitis in early childhood: consideration of the pathology of post-polio syndrome. AB - Post-polio syndrome (PPS) characterized by new neuromuscular problems can appear many years after acute poliomyelitis in polio survivors. We report a 77-year-old man with antecedent poliomyelitis who newly developed neuromuscular disease with a clinical course of 27 years, the final 10 years of which were characterized by apparent progression, thus raising doubt as to the clinical diagnosis of amyotrophic lateral sclerosis (ALS) following PPS. Pathologically, plaque-like, old poliomyelitis lesions were found almost exclusively in the lumbosacral cord, showing complete neuronal loss and glial scars in the anterior horns. Although less severe, neuronal loss and gliosis were also evident outside the old lesions, including the intermediate zone. Moreover, symmetrical degeneration of the corticospinal tracts, as evidenced by CD68 immunostaining, was a feature of the white matter of the lower spinal cord. In the motor cortex, loss of Betz cells was also confirmed. Synaptophysin immunostaining of the lumbosacral cord also revealed decreased expression outside the old lesions, excluding the posterior horn. Interestingly, decreased expression of synaptophysin was also evident in the cervical anterior horns, where no old lesions were observed. No Bunina bodies, TDP-43 inclusions, or Golgi fragmentation were found. Neurogenic atrophy was evident in the iliopsoas and scalenus muscles, and inclusion body myositis like changes were also observed in these muscles and the tongue. Was it possible to have diagnosed this patient as having ALS? We consider that the features in this case may have represented the pathology of long-standing and/or fatal PPS itself, and not ALS. PMID- 22672530 TI - Can abundant colloid exclude oncocytic (Hurthle cell) carcinoma in thyroid fine needle aspiration? Cytohistological correlation of 127 oncocytic (Hurthle cell) lesions. AB - OBJECTIVE: The objective of the present study was to find out whether the presence or absence of certain cytological features can exclude oncocytic (Hurthle cell) carcinoma in thyroid fine needle aspiration (FNA) to minimize unnecessary surgery. METHODS: Over a 17-year period, 127 hypercellular, oncocyte exclusive, lymphocyte-absent aspirates obtained via ultrasound-guided FNA with on site assessment had histology slides for review. The presence or absence of six cytological features (microfollicular arrangement, discohesive single cells, small cell dysplasia, large cell dysplasia, transgressing blood vessels and colloid) and one histological feature (macrofollicular component) were determined for each case independently by two cytopathologists. RESULTS: Histology showed 12 (9.4%) cases of Hashimoto thyroiditis, 23 (18.1%) oncocytic adenomatoid nodules in nodular goitre, 66 (52.0%) oncocytic adenomas and 26 (20.5%) oncocytic carcinomas (13 minimally invasive without angioinvasion, six minimally invasive with angioinvasion, seven widely invasive). Histologically, a macrofollicular component was present in seven of 26 (26.9%) oncocytic carcinomas, including one case with abundant thin colloid. A microfollicular arrangement, discohesive single cells, small cell dysplasia, large cell dysplasia and transgressing vessels were present in oncocytic carcinoma, oncocytic adenoma and oncocytic adenomatoid nodules in nodular goitre. CONCLUSIONS: A macrofollicular component is frequently present in oncocytic carcinoma, oncocytic adenoma and oncocytic adenomatoid nodules in nodular goitre. None of the cytological features studied, including abundant colloid, can exclude oncocytic carcinoma. Oncocytic carcinoma can only be excluded by thorough histological examination of thyroidectomy specimens. A molecular marker is needed to triage oncocytic lesions in thyroid FNA. PMID- 22672531 TI - The frequency of advanced adenoma in consulting patients: a nationwide survey in Iceland (2003-2006). AB - AIM: To assess the frequency of advanced colorectal adenomas in consulting patients in Iceland. METHOD: The histological configuration of colorectal adenomas (CRA) found in 3603 patients was classified into tubular (TA), villous (VA) and serrated (SA) and the degree of neoplastic severity into low-grade dysplasia (LGD), high-grade dysplasia (HGD), carcinoma in situ (CIS), intramucosal carcinoma (IMC) and submucosal carcinoma (SMC). Advanced CRA were those showing HGD, CIS, IMC and/or SMCs. In patients with two or more adenomas, the adenoma with the highest degree of epithelial neoplasia was selected to record cases. RESULTS: Between 2003 and 2006 a total of 19424 endoscopic examinations (13572 colonoscopies and 5852 sigmoidoscopies) were performed in Iceland (mean, 4856 endoscopies per year). At histology a mean of 759.3 CRA per year were found. Thus, CRA were found in 15.6% of the colorectal endoscopies performed per year. Out of the 3037 CRA studied, 67% were TA, 29% VA and the remaining 4% SA. LGD was present in 79%, HGD in 15%, CIS in 2.4%, IMC in 1.9% and SMC in 1.9%. Consequently, out of 3037 CRA investigated, 652 (21.5%) were advanced CRA; 71% of these showed HGD, 11% CIS, 9% IMC and 9% SMC. Two-thirds of the 652 advanced CRA were advanced VA, and more than three-quarters of 58 advanced CRA with SMC, were advanced VA. CONCLUSION: Advanced VA displaying intraepithelial neoplasia (HGD and CIS) showed a propensity to evolve into invasive carcinoma. Accordingly, VA displaying HGD and CIS might be regarded as biological markers for predicting colorectal cancer risk. This is the first study in which the frequency of CRA and advanced CRA detected in consulting patients is reported on a nationwide basis. PMID- 22672532 TI - Practice of breast self-examination and knowledge of breast cancer among female university students in Korea. AB - This study examined the practice of breast self-examination and knowledge of breast cancer among female university students in Korea. This was a cross sectional descriptive study. The participants were 2186 female university students in Korea. The Breast Cancer and Heredity Knowledge Scale was used. The collected data were analyzed through descriptive statistics, chi(2)-test, t-test, ANOVA, and logistic regression. Twenty-seven percent of students reported engaging in breast self-examination. The participants displayed a medium-level score (total score: 5.33 +/- 2.70, range: 0-11) on knowledge about breast cancer. Predictors for breast self-examination were age (odds ratio = 1.15, P < 0.001), major (odds ratio = 1.80, P < 0.001), and knowledge of breast cancer (odds ratio = 1.16, P < 0.001). This study was the sole nationwide-scale research that examined the practice of breast self-examination, related factors, and knowledge of breast cancer among female university students, as a representative sample of young Korean women. The results are valuable in developing educational programs that can increase knowledge related to breast cancer, as well as the practice of breast self-examination, to support health promotion among young women. PMID- 22672533 TI - Applying clinical staging to young people who present for mental health care. AB - AIM: The study aims to apply clinical staging to young people who present for mental health care; to describe the demographic features, patterns of psychological symptoms, disability correlates and clinical stages of those young people; and to report longitudinal estimates of progression from less to more severe stages. METHODS: The study uses cross-sectional and longitudinal assessments of young people managed in specialized youth clinics. On the basis of clinical records, subjects were assigned to a specific clinical 'stage' (i.e. 'help-seeking', 'attenuated syndrome', 'discrete disorder' or 'persistent or recurrent illness'). RESULTS: Young people (n = 209, mean age = 19.9 years (range = 12-30 years), 48% female) were selected from a broader cohort of n = 1483 subjects. Ten percent were assigned to the earliest 'help-seeking' stage, 54% to the 'attenuated syndrome' stage, 25% to the 'discrete disorder' stage and 11% to the later 'persistent or recurrent illness' stage. The interrater reliability of independent ratings at baseline was acceptable (kappa = 0.71). Subjects assigned to the 'attenuated syndrome' stage reported symptom and disability scores that were similar to those assigned to later stages. Longitudinally (median = 48 weeks), transition to later clinical stages were 11% of the 'help-seeking', 19% of the 'attenuated syndrome' and 33% of the 'discrete disorder' groups. CONCLUSION: Among young people presenting for mental health care, most are clinically staged as having 'attenuated syndromes'. Despite access to specialized treatment, a significant number progress to more severe or persistent disorders. PMID- 22672534 TI - Retinal ganglion cell survival and axon regeneration in WldS transgenic rats after optic nerve crush and lens injury. AB - BACKGROUND: We have previously shown that the slow Wallerian degeneration mutation, whilst delaying axonal degeneration after optic nerve crush, does not protect retinal ganglion cell (RGC) bodies in adult rats. To test the effects of a combination approach protecting both axons and cell bodies we performed combined optic nerve crush and lens injury, which results in both enhanced RGC survival as well as axon regeneration past the lesion site in wildtype animals. RESULTS: As previously reported we found that the Wld(S) mutation does not protect RGC bodies after optic nerve crush alone. Surprisingly, we found that Wld(S) transgenic rats did not exhibit the enhanced RGC survival response after combined optic nerve crush and lens injury that was observed in wildtype rats. RGC axon regeneration past the optic nerve lesion site was, however, similar in Wld(S) and wildtypes. Furthermore, activation of retinal glia, previously shown to be associated with enhanced RGC survival and axon regeneration after optic nerve crush and lens injury, was unaffected in Wld(S) transgenic rats. CONCLUSIONS: RGC axon regeneration is similar between Wld(S) transgenic and wildtype rats, but Wld(S) transgenic rats do not exhibit enhanced RGC survival after combined optic nerve crush and lens injury suggesting that the neuroprotective effects of lens injury on RGC survival may be limited by the Wld(S) protein. PMID- 22672536 TI - Development of an AFASS assessment and screening tool towards the prevention of mother-to-child HIV transmission (PMTCT) in sub-Saharan Africa--a Delphi survey. AB - BACKGROUND: The rate of mother-to-child transmission of HIV, occurring during pregnancy, delivery/labour and breastfeeding, still remains high in Sub-Saharan Africa (SSA). The World Health Organization recommends HIV infected mothers exclusively breastfeed their infants, unless replacement feeding is Acceptable, Feasible, Affordable, Sustainable and Safe (AFASS). Health care workers are responsible for providing counselling to mothers on the risks and benefits of infant feeding options allowing mothers to make an 'informed choice', but this role is challenging and mostly subjective. The aim of this study was to develop and content validate an AFASS assessment tool that could be used for infant feeding counselling in SSA. METHODS: An AFASS assessment tool was developed based on the evidence and tools available regarding why replacement feeding is not AFASS in SSA (15 questions). Fifty seven experts involved in PMTCT programmes in five SSA countries were approached to participate as members of the Delphi expert panel (purposive sampling and snowballing). A web-based survey, utilising a 4 point Likert scale, was employed to gain consensus (>75% agreement) from the expert panel following the Delphi technique. RESULTS: A final panel of 15 experts was obtained. Thirteen of the 15 questions in the tool achieved consensus agreement. Experts suggested some additional questions, and that double-barrelled questions were split. Consensus was achieved regarding the applicability and appropriateness of the tool within a SSA context. Experts all agreed that the tool will be useful for the purpose for which it was designed. Suggestions made by the expert panel were incorporated into the revised tool. CONCLUSIONS: The findings of this study confirm that this AFASS counselling tool may be appropriate and useful for SSA. Ideally the revised tool should be tested by providers of infant feeding advice with the aim of adoption into routine PMTCT programmes in SSA. Within the context of the 2010 WHO guidelines which advocate a public health rather than an individualised approach, it may inform the WHO process of improving counselling tools for health care workers involved in PMTCT programmes. PMID- 22672535 TI - Mucormycosis after allogeneic haematopoietic stem cell transplantation: a French Multicentre Cohort Study (2003-2008). AB - We conducted a nationwide retrospective study to evaluate clinical characteristics and outcome of mucormycosis among allogeneic haematopoietic stem cell transplant recipients. Twenty-nine patients were diagnosed between 2003 and 2008. Mucormycosis occurred at a median of 225 days after allogeneic haematopoietic stem cell transplant, and as a breakthrough infection in 23 cases. Twenty-six patients were receiving steroids, mainly for graft-versus-host disease treatment, while ten had experienced a prior post-transplant invasive fungal infection. Twenty-six patients received an antifungal treatment; surgery was performed in 12. Overall survival was 34% at 3 months and 17% at 1 year. PMID- 22672537 TI - Three-dimensional contrast echocardiography in assessing left ventricular diverticulum. AB - Congenital left ventricular (LV) diverticulum is a rare malformation that can be alone or in association with other congenital abnormalities. Since the several complications have been reported in association with LV diverticulum, as cardiac rupture, heart failure, and endocarditis, patients with LV diverticulum who are managed with conservative treatment would require regular checkups to ascertain the absence of such complications. We report a case of LV diverticulum in a 47 year-old man. He took the serial three-dimensional contrast echocardiography, which was reliable and readily available tool for defining LV diverticulum and monitoring the presence of complications. PMID- 22672538 TI - Successful pregnancy after the treatment of primary amenorrhea in a patient with non-classical congenital adrenal hyperplasia. AB - We describe a case of non-classical congenital adrenal hyperplasia (NCCAH) due to 21-hydroxylase deficiency in a 30-year-old Japanese woman who achieved pregnancy after treatment of primary amenorrhea. Hirsutism and clitoromegaly were present. Ultrasound examination showed polycystic appearance of the ovary. Luteinizing hormone-releasing hormone (LH-RH) test resulted in exaggerated LH response, showing a polycystic ovary syndrome (PCOS) pattern. The diagnosis was based on the elevated intial levels of 17-hydroxyprogesterone (55 ng/mL) and dihydroepiandosterone (7780 ng/mL). The first withdrawal bleeding occurred within 6 weeks after treatment with hydrocortisone (20 mg/day) combined with conjugated estrogens (1.25 mg/day) and medroxyprogesterone acetate (10 mg/day), which were continued for five courses. The bleeding remained cyclic every 28 days with maintenance doses of hydrocortisone. Subsequently, ovulation was induced using clomiphene citrate (100 mg/day). Pregnancy was achieved at the second attempt of ovulation induction and was within 10 months after initial presentation. Continuing hydrocortisone, the patient delivered a healthy baby at term. PMID- 22672539 TI - The HIV-1 Nef protein interacts with two components of the 40S small ribosomal subunit, the RPS10 protein and the 18S rRNA. AB - BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) Nef-encoded protein plays key functions at almost all stages of the viral life cycle, but its role in translation is largely unknown. METHODS: To determine the effect of Nef on translation we used an in vitro translation assay. The detection of Nef/RPS10 complexes and the presence of 18S rRNA and tRNAs in the complexes were performed by coimmunoprecipitation and RT-PCR assay. RESULTS: We observed that the HIV-1 Nef protein specifically impaired translation in vitro. We observed the interaction of Nef with RPS10 by coimmunoprecipitation assay. In addition 18S rRNA and tRNAs were present in the Nef/RPS10 complexes. CONCLUSIONS: Our results are consistent with a model in which the Nef protein by binding to two components of the 40S small ribosomal subunit, RPS10 and 18S rRNA, and to a lesser extent to tRNAs, could lead to decreased protein synthesis. PMID- 22672540 TI - Dealing with EBV sero-negative recipients: copy paste the CMV recipe?*. PMID- 22672541 TI - Anastomotic pseudoaneurysm after renal transplantation; a new hybrid approach with graft salvage. PMID- 22672542 TI - Age-dependent vulnerability to experimental acute pancreatitis is associated with increased systemic inflammation and thrombosis. AB - The severity and mortality rates of acute pancreatitis (AP) are significantly elevated in the elderly population. However, due to a lack of appropriate animal models, the underlying mechanisms for this age-dependent vulnerability remain largely unknown. The purpose of this study was to characterize a murine model of AP, which displays age-associated severity, and to use this model to identify pathophysiologies that are distinctive of the aged with AP. AP was induced in young (4-5 months), middle-aged (12-13 months), and aged (23-25 months) C57BL/6 mice by repeated injection of caerulein, a homologue of the gastrointestinal hormone cholecystokinin. Approximately 10% of aged mice died during AP, while young and middle-aged mice showed no mortality. Although both young and aged mice exhibited early signs of edema and inflammation in the pancreas, kidney, and lung, young mice showed signs of recovery within 24 h, while aged mice exhibited increasingly severe tissue damage and cell death. There was a significant age dependent increase in pancreatic neutrophil activation and systemic inflammation as assessed by pancreatic myeloperoxidase and plasma interleukin-6 (IL-6) concentration, respectively. Importantly, aged but not young mice with AP showed significantly elevated thrombosis in the lung and kidney as well as a marked increase in plasma concentration of plasminogen activator inhibitor-1 (PAI-1), a primary inhibitor of the fibrinolytic system. These results demonstrate that aging is associated with increased severity of AP characterized by augmented and prolonged pancreatic inflammation and the presence of multiple extra-pancreatic sequelae including thrombosis. PMID- 22672543 TI - Focal intrahepatic strictures: a review of diagnosis and management. AB - INTRODUCTION: Focal intrahepatic strictures are becoming more common owing to more prevalent and accurate cross-sectional imaging. However, data relating to their management are lacking. The purpose of the present review was to synthesize the current evidence regarding these lesions and to formulate a strategy for diagnosis and management. METHODS: A literature search of relevant terms was performed using Medline. References of papers were subsequently searched to obtain older literature. RESULTS: Focal intrahepatic strictures involve segmental hepatic ducts and/or left and right main hepatic ducts during their intrahepatic course. Most patients are asymptomatic while the minority present with vague abdominal pain or recurrent sepsis and only rarely with jaundice. Investigations used to distinguish benign from malignant aetiologies include blood tests (CEA, Ca19.9), imaging studies [ultrasonography (US), computed tomography (CT), magnetic resonance cholangiopancreatography (MRCP) and fluorodeoxyglucose positron emission tomography (FDG-PET)], endoscopic modalities [endoscopic retrograde cholangiopancreatography (ERCP)/endoscopic ultrasound (EUS)/cholangioscopy] and tissue sampling (brush cytology/biopsy). CONCLUSIONS: A focal intrahepatic stricture requires thorough investigation to exclude malignancy even in patients with a history of biliary surgery, hepatolithiasis or parasitic infection. If during the investigative process a diagnosis or suspicion of malignancy is demonstrated then surgical resection should be performed. If all diagnostic modalities suggest a benign aetiology, then cholangioscopy with targeted biopsies should be performed. PMID- 22672544 TI - Treatment and surveillance of polypoid lesions of the gallbladder in the United Kingdom. AB - OBJECTIVES: The increase in the routine use of abdominal imaging has led to a parallel surge in the identification of polypoid lesions in the gallbladder. True gallbladder polyps (GBP) have malignant potential and surgery can prevent or treat early gallbladder cancer. In an era of constraint on health care resources, it is important to ensure that surgery is offered only to patients who have appropriate indications. The aim of this study was to assess treatment and surveillance policies for GBP among hepatobiliary and upper gastrointestinal tract surgeons in the UK in the light of published evidence. METHODS: A questionnaire on the management of GBP was devised and sent to consultant surgeon members of the Association of Upper Gastrointestinal Surgeons (AUGIS) of Great Britain and Ireland with the approval of the AUGIS Committee. It included eight questions on indications for laparoscopic cholecystectomy and surveillance based on GBP (size, number, growth rate) and patient (age, comorbidities, ethnicity) characteristics. RESULTS: A total of 79 completed questionnaires were returned. The vast majority of surgeons (>75%) stated that they would perform surgery when a single GBP reached 10 mm in size. However, there was a lack of uniformity in the management of multiple polyps and polyp growth rate, with different surveillance protocols for patients treated conservatively. CONCLUSIONS: Gallbladder polyps are a relatively common finding on abdominal ultrasound scans. The survey showed considerable heterogeneity among surgeons regarding treatment and surveillance protocols. Although no randomized controlled trials exist, national guidelines would facilitate standardization, the formulation of an appropriate algorithm and appropriate use of resources. PMID- 22672545 TI - Portal biliopathy in patients with non-cirrhotic portal hypertension: does the type of surgery affect outcome? AB - OBJECTIVES: After portosystemic anastomoses for biliopathy, some patients continue to suffer biliary obstruction. The effects of splenectomy and devascularization of the abdominal oesophagus and upper stomach are unclear. The aim of the current study was to determine the features of portal biliopathy (PB) in patients with non-cirrhotic portal hypertension, and to investigate outcomes in these patients after surgical procedures. METHODS: A retrospective study of 56 patients who underwent surgery for PB during 1996-2010 was conducted. Data on presenting features, treatment received and outcomes were analysed. RESULTS: In total, 41 of these patients had extrahepatic portal venous obstruction and 15 had non-cirrhotic portal fibrosis. Forty patients underwent shunt surgery and 16 underwent splenectomy and devascularization. Median bilirubin levels fell from 1.8 mg/dl (range: 0.4-5.9 mg/dl) to 1.0 mg/dl (range: 0.3-5.4 mg/dl) after shunt surgery and from 1.9 mg/dl (range: 0.6-4.0 mg/dl) to 1.2 mg/dl (range: 0.6-5.2 mg/dl) after splenectomy-devascularization. On follow-up, five of 33 patients had persistent jaundice after successful shunt surgery. These patients had a history of multiple endoscopic stentings and three patients had demonstrated a dominant common bile duct stricture preoperatively. CONCLUSIONS: Portal biliopathy was reversed in 38 of 43 patients by either portosystemic shunting or splenectomy devascularization. In five patients, direct biliary decompressive procedures were required because of shunt blockage or a non-reversible biliary stricture. PMID- 22672546 TI - Outcomes in patients with indeterminate pulmonary nodules undergoing resection for colorectal liver metastases. AB - OBJECTIVES: This study aimed to assess outcomes in patients who underwent hepatic resection for colorectal liver metastases (CRLM) with subcentimetre indeterminate pulmonary nodules (IPN) and to devise a management pathway for these patients. METHODS: Patients undergoing CRLM resection from January 2006 to December 2010 were included. Survival differences following liver resection in patients with and without IPN were determined. RESULTS: A total of 184 patients were included, 30 of whom had IPN. There were no significant differences between the IPN and non IPN groups in terms of demographics, surgery and pathological factors. There were no significant differences between patients with and without IPN with respect to disease-free (P= 0.190) and overall (P= 0.710) survival. Fifteen patients with IPN progressed to metastatic lung disease over a median period of 10 months (range: 3-18 months); six of these patients underwent lung resection. Of the remaining 15 patients with IPN, eight showed no IPN progression and subsequent CT scans did not identify IPN in the remaining seven. CONCLUSIONS: Colorectal liver metastases patients with IPN who have resectable disease should be treated with liver resection and should be subject to intensive surveillance post-resection. Although 50% of these patients will progress to develop lung metastases, this does not appear to influence survival following liver resection. PMID- 22672547 TI - Is left lobe adult-to-adult living donor liver transplantation ready for widespread use? The US experience (1998-2010). AB - OBJECTIVES: Living donor liver transplantation (LDLT) is an accepted treatment for patients with end-stage liver disease. To minimize risk to the donor, left lobe (LL) LDLT may be an ideal option in adult LDLT. METHODS: This study assessed the outcomes of LL-LDLT compared with right lobe (RL) LDLT in adults (1998-2010) as reported to the United Network for Organ Sharing (UNOS) Organ Procurement and Transplantation Network (OPTN). RESULTS: A total of 2844 recipients of LDLT were identified. Of these, 2690 (94.6%) underwent RL-LDLT and 154 (5.4%) underwent LL LDLT. A recent increase in the number of LL-LDLTs was noted: average numbers of LL-LDLTs per year were 5.2 during 1998-2003 and 19.4 during 2004-2010. Compared with RL-LDLT recipients, LL-LDLT recipients were younger (mean age: 50.5 years vs. 47.0 years), had a lower body mass index (BMI) (mean BMI: 24.5 kg/m(2) vs. 26.8 kg/m(2)), and were more likely to be female (64.6% vs. 41.9%). Donors in LL LDLT had a higher BMI (mean BMI: 29.4 kg/m(2) vs. 26.5 kg/m(2)) and were less likely to be female (30.9% vs. 48.1%). Recipients of LL-LDLT had a longer mean length of stay (24.9 days vs. 18.2 days) and higher retransplantation rates (20.3% vs. 10.9%). Allograft survival in LL-LDLT was significantly lower than in RL-LDLT and there was a trend towards inferior patient survival. In Cox regression analysis, LL-LDLT was found to be associated with an increased risk for allograft failure [hazard ratio (HR): 2.39)] and inferior patient survival (HR: 1.86). CONCLUSIONS: The number of LL-LDLTs has increased in recent years. PMID- 22672548 TI - Portal vein embolization stimulates tumour growth in patients with colorectal cancer liver metastases. AB - OBJECTIVES: Portal vein embolization (PVE) can facilitate the resection of previously unresectable colorectal cancer (CRC) liver metastases. Bevacizumab is being used increasingly in the treatment of metastatic CRC, although data regarding its effect on post-embolization liver regeneration and tumour growth are conflicting. The objective of this observational study was to assess the impact of pre-embolization bevacizumab on liver hypertrophy and tumour growth. METHODS: Computed tomography scans before and 4 weeks after PVE were evaluated in patients who received perioperative chemotherapy with or without bevacizumab. Scans were compared with scans obtained in a control group in which no PVE was administered. Future liver remnant (FLR), total liver volume (TLV) and total tumour volume (TTV) were measured. Bevacizumab was discontinued >= 4 weeks before PVE. RESULTS: A total of 109 patients and 11 control patients were included. Portal vein embolization induced a significant increase in TTV: the right lobe increased by 33.4% in PVE subjects but decreased by 34.8% in control subjects (P < 0.001), and the left lobe increased by 49.9% in PVE subjects and decreased by 33.2% in controls (P= 0.022). A total of 52.8% of the study group received bevacizumab and 47.2% did not. There was no statistical difference between the two chemotherapy groups in terms of tumour growth. Median FLR after PVE was similar in both groups (28.8% vs. 28.7%; P= 0.825). CONCLUSIONS: Adequate liver regeneration was achieved in patients who underwent PVE. However, significant tumour progression was also observed post-embolization. PMID- 22672549 TI - Operative procedures for unresectable pancreatic cancer: does operative bypass decrease requirements for postoperative procedures and in-hospital days? AB - BACKGROUND: The optimal surgical management of patients found to have unresectable pancreatic cancer at open exploration remains unknown. METHODS: Records of patients who underwent non-therapeutic laparotomy for pancreatic cancer during 2000-2009 and were followed until death at Memorial Sloan-Kettering Cancer Center, New York, were reviewed. RESULTS: Over the 10-year study period, 157 patients underwent non-therapeutic laparotomy. Laparotomy alone was performed in 21% of patients; duodenal bypass, biliary bypass and double bypass were performed in 11%, 30% and 38% of patients, respectively. Complications occurred in 44 (28%) patients. Three (2%) patients died perioperatively. Postoperative interventions were required in 72 (46%) patients following exploration. The median number of inpatient days prior to death was 16 (interquartile range: 8-32 days). Proportions of patients requiring interventions were similar regardless of the procedure performed at the initial operation, as were the total number of inpatient days prior to death. Patients undergoing gastrojejunostomy required fewer postoperative duodenal stents and those undergoing operative biliary drainage required fewer postoperative biliary stents. CONCLUSIONS: In this study, duodenal, biliary and double bypasses in unresectable patients were not associated with fewer invasive procedures following non-therapeutic laparotomy and did not appear to reduce the total number of inpatient hospital days prior to death. Continued effort to identify unresectability prior to operation is justified. PMID- 22672550 TI - Ratio of remnant to total liver volume or remnant to body weight: which one is more predictive on donor outcomes? AB - BACKGROUND: Right lobe donations are known to expose the donors to more surgical risks than left lobe donations. In the present study, the effects of remnant volume on donor outcomes after right lobe living donor hepatectomies were investigated. METHODS: The data on 262 consecutive living liver donors who had undergone a right hepatectomy from January 2004 to June 2011 were retrospectively analysed. The influence of the remnant on the outcomes was investigated according to the two different definitions. These were: (i) the ratio of the remnant liver volume to total liver volume (RLV/TLV) and (ii) the remnant liver volume to donor body weight ratio (RLV/BWR). For RLV/TLV, the effects of having a percentage of 30% or below and for RLV/BWR, the effects of values lower than 0.6 on the results were investigated. RESULTS: Complication and major complication rates were 44.7% and 13.2% for donors with RLV/TLV of <=30%, and 35.9% and 9.4% for donors with RLV/BWR of < 0.6, respectively. In donors with RLV/TLV of <=30%, RLV/BWR being below or above 0.6 did not influence the results in terms of liver function tests, complications and hospital stay. The main impact on the outcome was posed by RLV/TLV of <=30%. CONCLUSION: Remnant volume in a right lobe living donor hepatectomy has adverse effects on donor outcomes when RLV/TLV is <=30% independent from the rate of RLV/BWR with a cut-off point of 0.6. PMID- 22672551 TI - Endoscopic ultrasound-guided choledoco-duodenostomy as an alternative to percutaneous trans-hepatic cholangiography. AB - BACKGROUND: Endoscopic ultrasonography (EUS)-guided choledochoduodenostomy (CDS) is an alternative to percutaneous transhepatic cholangiography (PTC) drainage in patients with an obstructed biliary system where conventional endoscopic retrograde biliary drainage (ERBD) has been unsuccessful. METHODS: Five EUS-CDS procedures were reviewed to assess whether successful decompression was achieved and maintained. RESULTS: There was technical success in each instance with no immediate complications. There was a significant fall in the median bilirubin of 164 mmol/l. The median follow-up was 44 days. In one patient the stent migrated with no adverse outcome. CONCLUSION: EUS-CDS is a viable alternative to PTC with fewer complications and comparable success rates. EUS-CDS may offer a future route for novel therapeutic advances. PMID- 22672552 TI - A typical feature of groove pancreatitis. PMID- 22672553 TI - Endoscopic ultrasound-guided treatment of visceral artery pseudoaneurysm. PMID- 22672556 TI - Late onset Li-Fraumeni Syndrome with bilateral breast cancer and other malignancies: case report and review of the literature. AB - BACKGROUND: Li-Fraumeni-Syndrome (LFS) is an autosomal-dominant, inherited tumour predisposition syndrome associated with heterozygous germline mutations in the TP53 gene. Patients with LFS are at a high risk to develop early-onset breast cancer and multiple malignancies, among which sarcomas are the most common. A high incidence of childhood tumours and close to 100% penetrance has been described. Knowledge of the genetic status of the TP53 gene in these patients is critical not only due to the increased risk of malignancies, but also because of the therapeutic implications, since a higher rate of radiation-induced secondary tumours in these patients has been observed. CASE REPORT: We report a patient with LFS harbouring heterozygous, pathogenic TP53 germline mutation, who was affected by four synchronous malignancies at the age of 40: a myxofibrosarcoma of the right upper arm, bilateral breast cancer and a periadrenal liposarcoma. Radiological treatments and a surveillance program were adjusted according to recommendations for LFS patients. CONCLUSION: Management of tumour treatment of patients with LFS is different to the general population because of their risk for secondary cancers in the radiation field. Screening procedures should take a possibly elevated risk for radiation induced cancer into account. PMID- 22672557 TI - Racial differences in B cell receptor signaling pathway activation. AB - BACKGROUND: Single-cell network profiling (SCNP) is a multi-parametric flow cytometry-based approach that simultaneously measures basal and modulated intracellular signaling activity in multiple cell subpopulations. Previously, SCNP analysis of a broad panel of immune signaling pathways in cell subsets within PBMCs from 60 healthy donors identified a race-associated difference in B cell anti-IgD-induced PI3K pathway activity. METHODS: The present study extended this analysis to a broader range of signaling pathway components downstream of the B cell receptor (BCR) in European Americans and African Americans using a subset of donors from the previously analyzed cohort of 60 healthy donors. Seven BCR signaling nodes (a node is defined as a paired modulator and intracellular readout) were measured at multiple time points by SCNP in PBMCs from 10 healthy donors [5 African Americans (36-51 yrs), 5 European Americans (36-56 yrs), all males]. RESULTS: Analysis of BCR signaling activity in European American and African American PBMC samples revealed that, compared to the European American donors, B cells from African Americans had lower anti-IgD induced phosphorylation of multiple BCR pathway components, including the membrane proximal proteins Syk and SFK as well as proteins in the PI3K pathway (S6 and Akt), the MAPK pathways (Erk and p38), and the NF-kappaB pathway (NF-kappaB). In addition to differences in the magnitude of anti-IgD-induced pathway activation, racial differences in BCR signaling kinetic profiles were observed. Further, the frequency of IgD+ B cells differed by race and strongly correlated with BCR pathway activation. Thus, the race-related difference in BCR pathway activation appears to be attributable at least in part to a race-associated difference in IgD+ B cell frequencies. CONCLUSIONS: SCNP analysis enabled the identification of statistically significant race-associated differences in BCR pathway activation within PBMC samples from healthy donors. Understanding race-associated contrasts in immune cell signaling responses may be one critical component for elucidation of differences in immune-mediated disease prevalence and treatment responses. PMID- 22672558 TI - Dialysis anticoagulation causing postoperative bleeding in a patient with systemic amyloidosis. PMID- 22672560 TI - Does e-cigarette consumption cause passive vaping? AB - Electronic cigarette consumption ('vaping') is marketed as an alternative to conventional tobacco smoking. Technically, a mixture of chemicals containing carrier liquids, flavors, and optionally nicotine is vaporized and inhaled. The present study aims at the determination of the release of volatile organic compounds (VOC) and (ultra)fine particles (FP/UFP) from an e-cigarette under near to-real-use conditions in an 8-m(3) emission test chamber. Furthermore, the inhaled mixture is analyzed in small chambers. An increase in FP/UFP and VOC could be determined after the use of the e-cigarette. Prominent components in the gas-phase are 1,2-propanediol, 1,2,3-propanetriol, diacetin, flavorings, and traces of nicotine. As a consequence, 'passive vaping' must be expected from the consumption of e-cigarettes. Furthermore, the inhaled aerosol undergoes changes in the human lung that is assumed to be attributed to deposition and evaporation. PRACTICAL IMPLICATIONS: The consumption of e-cigarettes marks a new source for chemical and aerosol exposure in the indoor environment. To evaluate the impact of e-cigarettes on indoor air quality and to estimate the possible effect of passive vaping, information about the chemical characteristics of the released vapor is needed. PMID- 22672559 TI - Prosthodontic treatment and medical considerations for a patient with Turner syndrome: a clinical report. AB - This clinical report describes a multidisciplinary approach in the rehabilitation of a 23-year-old Caucasian woman affected with Turner's syndrome and subsequently diagnosed with T4 Giant cell reparative granuloma of the right maxillary sinus. The surgical treatment included a maxillectomy and infratemporal fossa dissection followed by a free fibula palatal reconstruction, fibula bone graft of the orbital floor, dental implant placement, and prosthodontic rehabilitation. Prosthodontic planning and treatment considerations in an adult patient with Turner Syndrome are discussed. PMID- 22672561 TI - 'Myrosin cells' are not a prerequisite for aphid feeding on oilseed rape (Brassica napus) but affect host plant preferences. AB - The enzyme myrosinase (EC 3.2.3.1.147) is present in specialised myrosin cells and forms part of the glucosinolate-myrosinase system, also known as 'the mustard oil bomb', which has an important role in the defence system of cruciferous plants against insect pests. Transgenic Brassica napus MINELESS have been produced by transgenic ablation of myrosin cells. This prompted us to investigate the importance of myrosin cells in plant-aphid interactions. In order to study this, we challenged transgenic MINELESS and wild-type cultivar Westar seedlings with the aphids Brevicoryne brassicae (a specialist) and Myzus persicae (a generalist). Our study included aphid free-choice and aphid fecundity experiments. Data from these experiments showed that B. brassicae prefers wild type seedlings and M. persicae prefers MINELESS. B. brassicae and M. persicae showed significant variation in establishment on plants regardless of whether they were wild type or MINELESS and also differed significantly in affecting plant parts. Myrosinase activity in MINELESS control seedlings was 83.6% lower than the wild-type control seedlings. Infestation with either of the two aphid species induced myrosinase levels in both wild-type and MINELESS seedlings. Infestation with M. persicae reduced the concentration of most glucosinolates while B. brassicae had the opposite effect. B. brassicae enhanced the formation of glucosinolate hydrolysis products both in wild-type and MINELESS seedlings. However, M. persicae decreased All ITC but increased 3,4ETBut NIT in wild-type seedlings. Taken together, the investigation shows that the presence of myrosin cells affects the preference of generalist and specialist aphid species for Brassica napus plants. PMID- 22672562 TI - A CD3+ count-based thymoglobulin induction regimen permits delayed introduction of calcineurin inhibitors in kidney transplantation. AB - BACKGROUND: Withholding calcineurin inhibitors (CNIs) can be considered when graft function is inadequate following kidney transplantation (KT). Thymoglobulin (rATG) can be used to prevent acute rejection while CNIs are being withheld. Here, we report our results of a novel CNI-sparing induction protocol, which utilizes a CD3+ cell count-based rATG treatment regimen when delayed graft function (DGF) develops in the immediate postoperative period. METHODS: In a cohort of 153 consecutive deceased-donor KT recipients, all received a single intraoperative dose of basiliximab; 84 subsequently developed DGF and therefore received rATG (rATG+ group), while 69 demonstrated immediate graft function and received CNIs (rATG- group). RESULTS: In the rATG+ group, mean duration of therapy was 8.5+/-6.0 d, permitting CNI initiation to be delayed until postoperative day 10.3+/-6.2. Cumulative dose of rATG was only 5.1+/-4.5 mg/kg while targeting CD3+ counts of <=30 cells/mm3. CD3+ counts were reduced to a mean of 16.7+/-17.0 cells/mm3 during therapy. At one yr, patient and graft survival rates were 97.6% and 92.9%, respectively, while the frequency of infections and malignancies were not significantly increased compared to the rATG- group. CONCLUSION: A unique induction regimen successfully delayed CNI initiation by using modest doses of rATG to deplete CD3+ cells, while yielding excellent long term graft outcome without increased risk of infection or malignancy. PMID- 22672563 TI - Is testosterone treatment good for the prostate? Study of safety during long-term treatment. AB - INTRODUCTION: For men with androgen deficiency on testosterone replacement therapy (TRT), clinical concern relates to the development of prostate cancer (PCa). AIM: An updated audit of prostate safety from the UK Androgen Study was carried out to analyze the incidence of PCa during long-term TRT. MAIN OUTCOME MEASURES: Diagnosis of PCa in men receiving TRT, by serum prostate-specific antigen (PSA) testing and digital rectal examination (DRE), and its relation to different testosterone preparations. METHODS: One thousand three hundred sixty five men aged 28-87 (mean 55) years with symptomatic androgen deficiency and receiving TRT have been monitored for up to 20 years. All patients were prescreened for PCa by DRE and PSA along with endocrine, biochemical, hematological, and urinary profiles at baseline and every 6 months. Abnormal findings or rising PSA were investigated by transrectal ultrasound and prostate biopsy. The data were compared for the four different testosterone preparations used in TRT, including pellet implants, Restandol, mesterolone, and Testogel. RESULTS: Fourteen new cases of PCa were diagnosed at one case per 212 years treatment, after 2,966 man-years of treatment (one case per 212 years). Time to diagnosis ranged from 1 to 12 years (mean 6.3 years). All tumors were clinically localized and suitable for potentially curative treatment. Initiating testosterone treatment had no statistically significant effect on total PSA, free PSA or free/total PSA ratio, and any initial PSA change had no predictive relationship to subsequent diagnosis of cancer. CONCLUSIONS: The incidence of PCa during long-term TRT was equivalent to that expected in the general population. This study adds to the considerable weight of evidence that with proper clinical monitoring, testosterone treatment is safe for the prostate and improves early detection of PCa. Testosterone treatment with regular monitoring of the prostate may be safer for the individual than any alternative without surveillance. PMID- 22672564 TI - Genetic and environmental heterogeneity of residual variance of weight traits in Nellore beef cattle. AB - BACKGROUND: Many studies have provided evidence of the existence of genetic heterogeneity of environmental variance, suggesting that it could be exploited to improve robustness and uniformity of livestock by selection. However, little is known about the perspectives of such a selection strategy in beef cattle. METHODS: A two-step approach was applied to study the genetic heterogeneity of residual variance of weight gain from birth to weaning and long-yearling weight in a Nellore beef cattle population. First, an animal model was fitted to the data and second, the influence of additive and environmental effects on the residual variance of these traits was investigated with different models, in which the log squared estimated residuals for each phenotypic record were analyzed using the restricted maximum likelihood method. Monte Carlo simulation was performed to assess the reliability of variance component estimates from the second step and the accuracy of estimated breeding values for residual variation. RESULTS: The results suggest that both genetic and environmental factors have an effect on the residual variance of weight gain from birth to weaning and long yearling in Nellore beef cattle and that uniformity of these traits could be improved by selecting for lower residual variance, when considering a large amount of information to predict genetic merit for this criterion. Simulations suggested that using the two-step approach would lead to biased estimates of variance components, such that more adequate methods are needed to study the genetic heterogeneity of residual variance in beef cattle. PMID- 22672565 TI - Quality of life in asymptomatic children and adolescents before and after diagnosis of hypertrophic cardiomyopathy through family screening. AB - AIMS AND OBJECTIVES: The aim of this study was to measure quality of life (QoL) in asymptomatic children with hypertrophic cardiomyopathy (HCM) before and after diagnosis. BACKGROUND: Hypertrophic cardiomyopathy is a disease with a 50% risk of inheritance. Children at risk for serious complications can be diagnosed early with family screening, but before embarking on a screening programme, it is important to evaluate the psychosocial consequences of such screening. DESIGN: Prospective case-control study. METHODS: Quality of life was measured using a questionnaire by Lindstrom incorporating both objective and subjective aspects of the three spheres: external, interpersonal and personal, before and two years after diagnosis. The study group consisted of 13 children/adolescents (11 boys), median age 11 (5-18) years, with HCM diagnosed at family screening. All filled out a questionnaire before diagnosis and at follow-up. 41 healthy children/adolescents (22 boys), median age 11 (2-19) years with a first-degree relative diagnosed with HCM served as controls; 15/41 also completed follow-up data. RESULTS: The total QoL score for all spheres was similar in both groups at baseline and follow-up. In the interpersonal sphere, it was more common that children diagnosed with HCM had no siblings both at baseline (p = 0.002) and follow-up (p = 0.005). The family situation, social support and life events were unchanged from baseline to follow-up. Children with HCM had significantly more psychosomatic symptoms compared with controls at baseline (p < 0.05) but not at follow-up. Self-esteem, peer acceptance and satisfaction with school were unchanged and similar between groups. CONCLUSION: Family screening for HCM does not appear to negatively influence QoL. RELEVANCE TO CLINICAL PRACTICE: This study indicates that family screening of asymptomatic children and adolescents had no significant detrimental effects on QoL. This suggests that the benefits of finding symptomatic individuals at risk for serious complications outweigh concerns about screening asymptomatic individuals. PMID- 22672566 TI - Invasiveness of mouse embryos to human ovarian cancer cells HO8910PM and the role of MMP-9. AB - BACKGROUND: Our previous work found that mouse embryos could invade malignant cancer cells. In the process of implantation, embryo trophoblast cells express matrix metalloproteinases and the invasive ability of trophoblast cells is proportional to matrix metalloproteinase-9 protein expression. So the purpose of this study is to observe the effects of mouse embryos on human ovarian cancer cells in the co-culture environment in vitro and explore the possible mechanism of matrix metalloproteinase-9. METHODS: Several groups of human ovarian cancer cells HO8910PM were co-cultured with mouse embryos for different time duration, after which the effects of mouse embryos on morphology and growth behavior of HO8910PM were observed under the light microscope real-time or by H.E staining. Apoptosis was detected under laser confocal microscope by Annexin V-EGFP/PI staining in situ. Invasion ability of tumor cells was studied by transwell experiments. After matrix metalloproteinase 9 (MMP -9) activity was inhibited by MMP-9 Inhibitor I, the interaction between mouse embryos and human ovarian cancer cells HO8910PM was observed. RESULTS: Mouse embryos were able to invade co cultured human ovarian cancer cell layer which extended in the bottom of the culture dish, and gradually pushed away tumor cells to form their own growth space. The number of apoptosis tumor cells surrounding the embryo increased under laser confocal microscope. After co-cultured with mouse embryos, tumor cells invasive ability was lowered compared with the control group. After MMP-9 activity was inhibited, the interaction between mouse embryos and HO8910PM cells had no significant difference compared with the normal MMP-9 activity group. CONCLUSION: Mouse embryos were able to invade human ovarian cancer cells in vitro and form their own growth space, promote apoptosis of human ovarian cancer cells and lower their invasive ability. The mouse embryo was still able to invade human ovarian cancer cells after MMP-9 activity was inhibited. PMID- 22672567 TI - Apparent signal of competition limiting diversification after ecological transitions from marine to freshwater habitats. AB - Adaptive radiations are typically triggered when a lineage encounters a significant range of open niche space (ecological opportunity), stemming from colonisation of new areas, extinction of competitors or key innovations. The most well-known of these is the colonisation of new areas, through either dispersal into new regions or the invasion of novel ecological regimes. One aspect of ecological opportunity that has rarely been studied, however, is the extent to which pre-existent competitors act to limit diversification in newly colonised adaptive zones. Herein, we show that in multiple geographically independent invasions of freshwaters by marine Sea Catfishes (Ariidae), rates of both morphological disparification and lineage diversification are inversely related to the presence and diversity of other freshwater fish lineages. Only in one region (Australia-New Guinea) with an otherwise depauperate freshwater fauna, has an ariid invasion gained any substantial traction. This is true at both regional and community scales, suggesting that competitive constraints may be an important factor regulating adaptive radiation. PMID- 22672569 TI - Long-term outcome of the use of intravesical botulinum toxin for the treatment of overactive bladder (OAB). AB - OBJECTIVES: To assess the long-term compliance with repeated injections of intravesical botulinum toxin (BT) in a 'real-life' mixed population of patients with idiopathic detrusor overactivity and neurogenic detrusor overactivity. To identify the reasons why patients discontinued BT therapy and to explore the outcomes of those patients who did discontinue treatment. PATIENTS AND METHODS: Retrospective evaluation of the case notes of a series of patients who had received intravesical BT treatment at a large UK teaching hospital. No antibiotic prophylaxis was given for the procedure. RESULTS: Over a period of 7 years, 268 patients were initiated on intravesical BT treatment for overactive bladder (OAB) at our institution, with 137 followed up for >=36 months, with 80 patients having >=60 months follow-up after their first injection. Almost two-thirds of patients (61.3%) had discontinued intravesical BT therapy at 36 months, with a 63.8% discontinuation rate at 60 months. The main reasons for discontinuation were tolerability issues, mainly urinary tract infections and the need for clean intermittent self-catheterisation. Primary and secondary losses of efficacy were of secondary importance. Most of the patients that discontinued have remained under urology care and now receive alternative methods of treatment. CONCLUSIONS: Intravesical BT therapy is an effective short-term treatment for OAB. With time, two-thirds of patients discontinued treatment usually because of the tolerability issues associated with treatment. PMID- 22672568 TI - A genome-wide association study of venous thromboembolism identifies risk variants in chromosomes 1q24.2 and 9q. AB - OBJECTIVES: To identify venous thromboembolism (VTE) disease-susceptibility genes. PATIENTS AND METHODS: We performed in silico genome wide association scan (GWAS) analyses using genotype data imputed to approximately 2.5 million single nucleotide polymorphisms (SNPs) from adults with objectively-diagnosed VTE (n=1503), and controls frequency matched on age and gender (n=1459; discovery population). Single-nucleotide polymorphisms exceeding genome-wide significance were replicated in a separate population (VTE cases, n=1407; controls, n=1418). Genes associated with VTE were re-sequenced. RESULTS: Seven SNPs exceeded genome wide significance (P<5*10(-8)): four on chromosome 1q24.2 (F5 rs6025 [factor V Leiden], BLZF1 rs7538157, NME7 rs16861990 and SLC19A2 rs2038024) and three on chromosome 9q34.2 (ABO rs2519093 [ABO intron 1], rs495828, rs8176719 [ABO blood type O allele]). The replication study confirmed a significant association of F5, NME7 and ABO with VTE. However, F5 was the main signal on 1q24.2 as only ABO SNPs remained significantly associated with VTE after adjusting for F5 rs6025. This 1q24.2 region was shown to be inherited as a haplotype block. ABO re-sequencing identified 15 novel single nucleotide variations (SNV) in ABO intron 6 and the ABO 3' UTR that were strongly associated with VTE (P<10(-4)) and belonged to three distinct linkage disequilibrium (LD) blocks; none were in LD with ABO rs8176719 or rs2519093. Our sample size provided 80% power to detect odds ratios (ORs)=2.0 and 1.51 for minor allele frequencies=0.05 and 0.5, respectively (alpha=1*10(-8); 1% VTE prevalence). CONCLUSIONS: Apart from F5 rs6025, ABO rs8176719, rs2519093 and F2 rs1799963, additional common and high VTE-risk SNPs among whites are unlikely. PMID- 22672570 TI - A 77-year-old man with sudden onset of left hand weakness and hematuria. PMID- 22672571 TI - Survival outcome of patients with screening versus symptomatically detected colorectal cancers. AB - AIM: The national Bowel Cancer Screening Programme has been rolled out nationwide following pilot screening in two health authorities in the UK. The aim of this study was to define overall 5-year survival of screen detected cancers and to compare the overall survival outcome of screened vs symptomatic patients over a 10-year period. METHOD: All patients with colorectal cancer treated at one trust in patients of screening age (50-69 years) during the pilot screening programme (2000-2008) were analysed. Patients were defined as screen detected or symptomatically detected. Disease pathology and recurrence data were obtained from the hospital's computerized results reporting system and mortality was cross matched with data from the West Midlands Cancer Intelligence Network. RESULTS: In all, 633 patients aged 50-69 were identified in the study period; 155 patients had a screen detected cancer and 478 did not. A log-rank test completed on survival outcomes indicated that survival was significantly worse in the symptomatic group. This difference persisted if only patients treated with curative intent were considered. CONCLUSION: Survival outcome was significantly better in the screened vs the symptomatic population in all groups and also in those treated for curative intent. There was a trend towards better survival for screen detected cancer when compared stage for stage. PMID- 22672572 TI - Cytological features of diffuse large B-cell lymphoma can mimic metastatic carcinoma on fine needle aspiration cytology. PMID- 22672573 TI - Physical therapy in Huntington's disease--toward objective assessments? AB - BACKGROUND AND PURPOSE: Physical therapy is recommended for the treatment of Huntington's disease, but reliable studies investigating its efficacy are almost non-existent. This may in part be due to the lack of suitable outcome measures. Therefore, we investigated the applicability of novel quantitative and objective assessments of motor dysfunction in the evaluation of physical therapy interventions aimed at improving gait and posture. METHODS: Twelve patients with Huntington disease received a predefined twice-weekly intervention focusing on posture and gait over 6 weeks. The GAITRite mat and a force plate were used for objective and quantitative assessments. The Unified Huntingtons Disease Rating Scale Total Motor Score, the timed Up &Go test, and the Berg Balance Scale were used as clinical outcome measures. RESULTS: Significant improvements were seen in GAITRite measures after therapy. Improvements were also seen in the Up & Go test and Berg Balance Scale, whereas force plate measures and Total Motor Scores did not change. CONCLUSIONS: The results suggest that physical therapy has a positive effect on gait in Huntington's disease. The study shows that objective and quantitative measures of gait and posture may serve as endpoints in trials assessing the efficacy of physical therapy. They should be explored further in larger trials applying a randomized controlled setting. PMID- 22672574 TI - Coronary artery calcium scanning in asymptomatic patients with diabetes mellitus: a paradigm shift. AB - Coronary artery calcium (CAC) is the most powerful cardiac risk prognosticator in the asymptomatic population, with consistent superiority to all risk factor-based paradigms. More recently, the strong prognostic value of changes in CAC has been demonstrated. The application of CAC to asymptomatic patients with diabetes mellitus (DM), all of whom have been presumed to be of high risk, has yielded a range of risks from low to high, proportional to the amount of calcified plaque, as in patients without DM. These risks are higher than in non-diabetic patients at corresponding CAC levels, except for those without CAC who have the same low risk as non-diabetic patients. In addition, the value of serial scanning to assess plaque progression and prognosis in people with DM has been demonstrated. Therefore, we propose that: (i) DM is not a coronary artery disease equivalent; (ii) CAC can be used routinely in all asymptomatic diabetic patients >40 years of age, as proposed by American College of Cardiology/American heart Association guidelines; and (iii) serial CAC scanning be considered for evaluation of the response to therapy. PMID- 22672575 TI - Enhancement of musculocutaneous nerve reinnervation after vascular endothelial growth factor (VEGF) gene therapy. AB - BACKGROUND: Vascular endothelial growth factor (VEGF) is not only a potent angiogenic factor but it also promotes axonal outgrowth and proliferation of Schwann cells. The aim of the present study was to quantitatively assess reinnervation of musculocutaneous nerve (MCN) stumps using motor and primary sensory neurons after plasmid phVEGF transfection and end-to-end (ETE) or end-to side (ETS) neurorrhaphy. The distal stump of rat transected MCN, was transfected with plasmid phVEGF, plasmid alone or treated with vehiculum and reinnervated following ETE or ETS neurorrhaphy for 2 months. The number of motor and dorsal root ganglia neurons reinnervating the MCN stump was estimated following their retrograde labeling with Fluoro-Ruby and Fluoro-Emerald. Reinnervation of the MCN stumps was assessed based on density, diameter and myelin sheath thickness of regenerated axons, grooming test and the wet weight index of the biceps brachii muscles. RESULTS: Immunohistochemical detection under the same conditions revealed increased VEGF in the Schwann cells of the MCN stumps transfected with the plasmid phVEGF, as opposed to control stumps transfected with only the plasmid or treated with vehiculum. The MCN stumps transfected with the plasmid phVEGF were reinnervated by moderately higher numbers of motor and sensory neurons after ETE neurorrhaphy compared with control stumps. However, morphometric quality of myelinated axons, grooming test and the wet weight index were significantly better in the MCN plasmid phVEGF transfected stumps. The ETS neurorrhaphy of the MCN plasmid phVEGF transfected stumps in comparison with control stumps resulted in significant elevation of motor and sensory neurons that reinnervated the MCN. Especially noteworthy was the increased numbers of neurons that sent out collateral sprouts into the MCN stumps. Similarly to ETE neurorrhaphy, phVEGF transfection resulted in significantly higher morphometric quality of myelinated axons, behavioral test and the wet weight index of the biceps brachii muscles. CONCLUSION: Our results showed that plasmid phVEGF transfection of MCN stumps could induce an increase in VEGF protein in Schwann cells, which resulted in higher quality axon reinnervation after both ETE and ETS neurorrhaphy. This was also associated with a better wet weight biceps brachii muscle index and functional tests than in control rats. PMID- 22672576 TI - Promoting walking among office employees - evaluation of a randomized controlled intervention with pedometers and e-mail messages. AB - BACKGROUND: The purpose of the study was to evaluate a 6-month intervention to promote office-employees' walking with pedometers and e-mail messages. METHODS: Participants were recruited by 10 occupational health care units (OHC) from 20 worksites with 2,230 employees. Voluntary and insufficiently physically active employees (N = 241) were randomized to a pedometer (STEP, N = 123) and a comparison group (COMP, N = 118). STEP included one group meeting, log-monitored pedometer-use and six e-mail messages from OHC. COMP participated in data collection. Reach, effectiveness, adoption, implementation, maintenance (RE-AIM) and costs were assessed with questionnaires (0, 2, 6, 12 months), process evaluation and interviews (12 months). RESULTS: The intervention reached 29% (N = 646) of employees in terms of participation willingness. Logistic regression showed that the proportion of walkers tended to increase more in STEP than in COMP at 2 months in "walking for transportation" (Odds ratio 2.12, 95%CI 0.94 to 4.81) and at 6 months in "walking for leisure" (1.86, 95%CI 0.94 to 3.69). Linear model revealed a modest increase in the mean duration of "walking stairs" at 2 and 6 months (Geometric mean ratio 1.26, 95%CI 0.98 to 1.61; 1.27, 0.98 to 1.64). Adoption and implementation succeeded as intended. At 12 months, some traces of the intervention were sustained in 15 worksites, and a slightly higher number of walkers in STEP in comparison with COMP was observed in "walking stairs" (OR 2.24, 95%CI 0.94 to 5.31) and in "walking for leisure" (2.07, 95%CI 0.99 to 4.34). The direct costs of the intervention were 43 Euros per participant. CONCLUSIONS: The findings indicate only modest impact on some indicators of walking. Future studies should invest in reaching the employees, minimizing attrition rate and using objective walking assessment. TRIAL REGISTERATION: ISRCTN79432107. PMID- 22672577 TI - Live/real time three-dimensional transesophageal echocardiography in the assessment of aortic root patch dehiscence. AB - We report a 66-year-old man who underwent partial reconstruction of the aortic root and presented with heart failure 2 months after the procedure. We used live/real time three-dimensional transesophageal echocardiography (3DTEE) to detect the exact site of the dehiscence flap and extent of the leakage. This information could be valuable to surgeons. PMID- 22672578 TI - Multimodal quantitative analysis of early pulsed-dye laser treatment of scars at a pediatric burn hospital. AB - BACKGROUND: The pulsed-dye laser (PDL) is a potential adjunctive therapy for treatment of hyperemic and hypertrophic scars. OBJECTIVE: To compare the effects of early PDL treatment plus compression therapy (CT) with those of CT alone in patients undergoing burn scar reconstruction with split-thickness grafts on an extremity. METHODS: Laser treatments were applied to one half of the graft seam. Standard CT was applied to both halves. Laser treatment was repeated at 6-week intervals until one half reached sufficient clinical improvements. Each half was evaluated just before treatments using quantitative measures of color, scar height, biomechanical properties and clinical features using the Vancouver Scar Scale (VSS). RESULTS: Less quantitative scar erythema and height and greater tissue elasticity were observed after two or three treatments for PDL plus compression than with compression alone. VSS scores showed greater improvement for vascularity, pliability, pigmentation, and height for PDL plus compression than for compression alone. CONCLUSION: PDL treatment in combination with CT appears to reduce scar hyperemia and height and normalize the biomechanical properties of burn-related scars. PMID- 22672580 TI - Reproductive outcome of couples with recurrent miscarriage and balanced chromosomal abnormalities. AB - AIM: Despite known association of parental carriers of structural chromosomal rearrangements with a history of recurrent pregnancy loss (RPL), the possibility of having a miscarriage due to an unbalanced chromosomal aberration remains unknown. There has been limited research on the reproductive outcome of such couples. The present study was done to report the distribution of structural chromosome rearrangements in patients experiencing RPL and to describe subsequent pregnancy outcomes in the carriers. MATERIAL AND METHODS: Chromosomal analysis was performed on blood samples from 788 individuals with RPL and distribution of chromosomal anomalies was studied. In couples found to have chromosomal rearrangements, pregnancy outcomes were recorded over 2 years. In the subsequent pregnancy, cytogenetic analysis was done on amniotic fluid (obtained at 16-20 weeks), or on miscarriage specimens (in pregnancies that failed to continue). RESULTS: Chromosomal rearrangements were identified in 6.8% (54/788) cases (including 5.9% reciprocal translocations, 0.7% Robertsonian translocations, and 0.1% inversions). The risk of having a chromosomal aberration was not related to the number of previous miscarriages. Over the next 2 years, two-thirds of the 49 documented pregnancies resulted in a normal live birth, and one-third miscarried. Most miscarriages (56.2%) were euploid, two were trisomic and 12.5% had an unbalanced translocation. CONCLUSION: In couples with no other cause of RPL other than a structural chromosomal rearrangement, nearly two-thirds are likely to have a normal outcome in subsequent pregnancy. Couples with pure abortion histories carry higher risk for cytogenetic abnormality than couples with normal children in addition to abortions. PMID- 22672579 TI - Nutrient-dependent requirement for SOD1 in lifespan extension by protein restriction in Drosophila melanogaster. AB - Reactive oxygen species (ROS) modulate aging and aging-related diseases. Dietary composition is critical in modulating lifespan. However, how ROS modulate dietary effects on lifespan remains poorly understood. Superoxide dismutase 1 (SOD1) is a major cytosolic enzyme responsible for scavenging superoxides. Here we investigated the role of SOD1 in lifespan modulation by diet in Drosophila. We found that a high sugar-low protein (HS-LP) diet or low-calorie diet with low sugar content, representing protein restriction, increased lifespan but not resistance to acute oxidative stress in wild-type flies, relative to a standard base diet. A low sugar-high protein diet had an opposite effect. Our genetic analysis indicated that SOD1 overexpression or dfoxo deletion did not alter lifespan patterns of flies responding to diets. However, sod1 reduction blunted lifespan extension by the HS-LP diet but not the low-calorie diet. HS-LP and low calorie diets both reduced target of rapamycin (TOR) signaling and only the HS-LP diet increased oxidative damage. sod1 knockdown did not affect phosphorylation of S6 kinase, suggesting that SOD1 acts in parallel with or downstream of TOR signaling. Surprisingly, rapamycin decreased lifespan in sod1 mutant but not wild type males fed the standard, HS-LP, and low-calorie diets, whereas antioxidant N acetylcysteine only increased lifespan in sod1 mutant males fed the HS-LP diet, when compared to diet-matched controls. Our findings suggest that SOD1 is required for lifespan extension by protein restriction only when dietary sugar is high and support the context-dependent role of ROS in aging and caution the use of rapamycin and antioxidants in aging interventions. PMID- 22672581 TI - A case of congenital plasmodium vivax malaria from a temperate region in Central China. AB - In February 2011, a rare case of congenital Plasmodium vivax malaria was diagnosed in a temperate region of Central China. An infant developed intermittent fever 20 days after delivery. Since this occurred during the non transmission winter season in a low malaria endemic region and the infant's mother did not have a clear malaria history or showed malaria symptoms at the time of the delivery, malaria infection was not suspected at the beginning. Later, on suspicion of potential malignant haematological illness due to persistence of the fever, bone marrow smear was examined, which revealed infection by P. vivax parasite. This rare case of congenital vivax malaria underlines that malaria diagnosis might need to be included in the healthcare of neonates born in vivax-endemic areas. PMID- 22672582 TI - Identification and expression analysis of components involved in rice Xa21 mediated disease resistance signalling. AB - Rice Xa21 gene encodes a receptor-like kinase that confers broad-spectrum resistance against Xanthomonas oryzae pv. oryzae (Xoo). Recently, a number of genes involved in the Xa21-mediated disease resistance pathway have been identified. Based on our previous data and the literature, we chose 16 candidate proteins and made corresponding antibodies. Using Western blotting, we systematically investigated the expression profile of the proteins in Xa21 mediated disease resistance response. We found nine proteins with altered expression. We further compared their expression in resistance, susceptible and mock responses, and found that GST expression was up-regulated during the resistance process, indicating GST is a positive regulator in resistance responses. ATPsB expression was down-regulated during both the resistance and susceptible response processes, although it was higher in the resistance response than that in the susceptible response. The total amount of MYB, GAPDH, CatB, Trx and NB-ARC proteins was lower in the resistance than in the susceptible response, but their abundance per unit bacteria in the resistance response was still higher than in the susceptible response, suggesting that these proteins might be positive regulators in the resistance response. In addition, expression of another ERF was induced by inoculation with bacterial blight pathogen, and expression of Zf-LSD1 was activated by wounding stress alone. Interestingly, most proteins showed similar altered expression patterns in the resistance and susceptible responses, but differed to some extents, implying that both responses might share common molecular mechanisms. This study revealed evidence of resistance-related protein expression, providing a foundation for better understanding of their functions. PMID- 22672583 TI - Development of specific and quantitative real-time detection PCR and immunoassays for lambda3-interferon. AB - AIM: Single nucleotide polymorphisms (SNP) around interferon (IFN)-lambda3 have been associated with the response to pegylated IFN-alpha treatment for chronic hepatitis C. Specific quantification methods for IFN-lambda3 are required to facilitate clinical and basic study. METHODS: Gene-specific primers and probes for IFN-lambda1, 2 and 3 were designed for real-time detection PCR (RTD-PCR). Dynamic range and specificity were examined using specific cDNA clones. Total RNA from hematopoietic and hepatocellular carcinoma cell lines was prepared for RTD PCR. Monoclonal antibodies were developed for the IFN-lambda3-specific immunoassays. The immunoassays were assessed by measuring IFN-lambda3 in serum and plasma. RESULTS: The RTD-PCR had a broad detection range (10-10(7) copies/assay) with high specificity (~10(7) -fold specificity). Distinct expression profiles were observed in several cell lines. Hematopoietic cell lines expressed high levels of IFN-lambda compared with hepatocellular carcinoma cells, and Sendai virus infection induced strong expression of IFN-lambda. The developed chemiluminescence enzyme immunoassays (CLEIA) detected 0.1 pg/mL of IFN-lambda3 and showed a wide detection range of 0.1-10 000 pg/mL with little or no cross reactivity to IFN-lambda1 or IFN-lambda2. IFN-lambda3 could be detected in all the serum and plasma samples by CLEIA, with median concentrations of 0.92 and 0.86 pg/mL, respectively. CONCLUSION: Our newly developed RTD-PCR and CLEIA assays will be valuable tools for investigating the distribution and functions of IFN-lambda3, which is predicted to be a marker for predicting outcome of therapy for hepatitis C or other virus diseases. PMID- 22672584 TI - A prospective, controlled clinical trial evaluating the clinical radiological and aesthetic outcome after 5 years of immediately placed implants in sockets exhibiting periapical pathology. AB - OBJECTIVE: The aim was to compare the clinical, aesthetic and radiological outcome of immediately placed implants in sockets with or without periapical pathology 5 years after placement. MATERIALS AND METHODS: Twenty-seven patients were followed 5 years after immediate implant placement (test-group: 12 patients with periapical pathologies; control-group: 15 patients without periapical pathology). Clinical (FMBS, FMPS, CAL, keratinized mucosa), aesthetical (length of clinical crown, Papilla index), and radiological (vertical distance implant shoulder to first bone to implant contact (IS-BIC)) parameters were assessed. Both 95% confidence intervals, as well as results of statistical tests (one sample, two-sample, paired t-test) were provided. RESULTS: After 5 years the implant survival rate was 100% for all 27 implants. In the test group the width of the keratinized mucosa increased significantly over the observation period (0.8 +/- 1.0 mm). Concerning aesthetic parameters at the 3-month as well as at the 5-year examination no statistically significant difference could be found between the two groups. In the control-group the papilla mesial and distal to the implant increased statistically significant during the observation period by 0.5 +/- 0.5 and 0.4 +/- 0.6 index score points, respectively. The position of the gingival margin at the implant site and the two neighboring teeth remained stable. At the 5-year visit IS-BIC measured between 1.4 +/- 0.5 mm (mesial, control) and 1.7 +/- 0.7 mm (distal, test), no significant difference could be found between the two groups. Over the observation period no statistically significant change of IS-BIC could be found in the test- as well as in the control-group. None of the examined radiographs revealed any signs of retrograde peri-implantitis. CONCLUSION: The replacement of teeth exhibiting periapical pathologies by implants placed immediately after tooth extraction can be a successful treatment modality with no disadvantages in clinical, aesthetical and radiological parameters to immediately placed implants into healthy sockets. PMID- 22672585 TI - Nursing interventions for improving nutritional status and outcomes of stroke patients: descriptive reviews of processes and outcomes. AB - BACKGROUND: Stroke produces many effects that impact eating. Nutrition is fundamental for recovery and rehabilitation, but the nursing nutritional role and associated outcomes have not been delineated. AIMS: (1) To identify nursing interventions intended to improve nutritional status and related outcomes of stroke survivors, and (2) To examine the outcomes of identified nursing interventions on nutrition-related outcomes, including dietary intake, functional status, complications, activities of daily living, mortality, and quality of life for stroke survivors. METHODS: A modified version of Cochrane literature searching and review methods was used to identify studies that described and evaluated nursing nutritional interventions for adult stroke patients in hospital and community settings. A minimum of 10 years content of seven databases and nine journals was searched to March 2011. Findings were presented descriptively. RESULTS: In total 27 papers from 26 studies were included: 5 randomized controlled trials, 5 clinical trials, 6 quasi-experiments, 4 case studies, and 6 qualitative/observational studies. Stroke nursing nutritional care encompassed screening of nutritional status and swallowing function; assessment of nutritional characteristics and preferences; referral; mealtime organization, supervision and monitoring; mealtime assistance and feeding skills. Nurses individualized care, coordinated or managed meal delivery and enteral feeding systems, were responsible for the dining environment and conduct of mealtimes; they taught staff, patients, and carers. There was little indication of integrated or psychosocial nursing nutritional care, or concepts, theories or models of nursing nutritional care. Many interventions were described but not evaluated. Little high quality evidence was of available. CONCLUSIONS: This review indicated the parameters of nursing nutritional care, and provided a framework for future research. A functional, supportive, and educational nursing nutritional role was described but little evidence was of sufficient quality to support policy and practice development or inform education. Nutritional care was revealed as an essential but under-recognized element of stroke nursing. PMID- 22672586 TI - The addition of sitagliptin to ongoing metformin therapy significantly improves glycemic control in Chinese patients with type 2 diabetes. AB - BACKGROUND: The present study was conducted to evaluate the efficacy, safety and tolerability of sitagliptin added to ongoing metformin therapy in Chinese patients with type 2 diabetes (T2DM) who failed to achieve adequate glycemic control with metformin monotherapy. METHODS: After a metformin titration/stabilization period and a 2-week, single-blind, placebo run-in period, 395 Chinese patients with T2DM aged 25-77 years (baseline HbA1c 8.5%) were randomized (1:1) to double-blind placebo or sitagliptin 100 mg q.d. added to ongoing open-label metformin (1000 or 1700 mg/day) for 24 weeks. RESULTS: Significant (P < 0.001) changes from baseline in HbA1c (-0.9%), fasting plasma glucose (-1.2 mmol/L), and 2-h post-meal plasma glucose (-1.9 mmol/L) were seen with sitagliptin compared with placebo. There were no significant differences between sitagliptin and placebo in the incidence of hypoglycemia or gastrointestinal adverse events. A small decrease from baseline body weight was observed in the placebo group compared with no change in the sitagliptin group (between-group difference 0.5kg; P=0.018). CONCLUSIONS: The addition of sitagliptin 100 mg to ongoing metformin therapy significantly improved glycemic control and was generally well tolerated in Chinese patients with T2DM who had inadequate glycemic control on metformin alone. PMID- 22672587 TI - Cluster-randomised trial to evaluate the 'Change for Life' mass media/ social marketing campaign in the UK. AB - BACKGROUND: Social marketing campaigns offer a promising approach to the prevention of childhood obesity. Change4Life (C4L) is a national obesity prevention campaign in England. It included mass media coverage aiming to reframe obesity into a health issue relevant to all and provided the opportunity for parents to complete a brief questionnaire ('How are the Kids') and receive personalised feedback about their children's eating and activity. Print and online C4L resources were available with guidance about healthy eating and physical activity. The study aims were to examine the impact of personalised feedback and print material from the C4L campaign on parents' attitudes and behaviours about their children's eating and activity in a community-based cluster-randomised controlled trial. METHODS: Parents of 5-11 year old children were recruited from 40 primary schools across England. Schools were randomised to intervention or control ('usual care'). Basic demographic data and brief information about their attitudes to their children's health were collected. Families in intervention schools were mailed the C4L print materials and the 'How are the Kids' questionnaire; those returning the questionnaire were sent personalised feedback and others received generic materials. Outcomes included awareness of C4L, attitudes to the behaviours recommended in C4L, parenting behaviours (monitoring and modelling), and child health behaviours (diet, physical activity and television viewing). Follow-up data were collected from parents by postal questionnaire after six months. Qualitative interviews were carried out with a subset of parents (n = 12). RESULTS: 3,774 families completed baseline questionnaires and follow-up data were obtained from 1,419 families (37.6%). Awareness was high in both groups at baseline (75%), but increased significantly in the intervention group by follow-up (96% vs. 87%). Few parents (5.2% of the intervention group) returned the questionnaire to get personalised feedback. There were few significant group differences in parental attitudes or parenting and child health behaviours at follow-up. Physical activity was rated as less important in the intervention group, but a significant group-by socioeconomic status (SES) interaction indicated that this effect was confined to higher SES families. Similar interactions were also seen for physical activity monitoring and child television time; with adverse effects in higher SES families and no change in the lower SES families. Effects were little better in families that completed the questionnaire and received personalised feedback. At interview, acceptability of the intervention was modest, although higher in lower SES families. CONCLUSIONS: The C4L campaign materials achieved increases in awareness of the campaign, but in this sample had little impact on attitudes or behaviour. Low engagement with the intervention appeared a key issue. TRIAL REGISTRATION NUMBER: Current Controlled Trials ISRCTN00791709. PMID- 22672588 TI - Heterogeneous virulence of pandemic 2009 influenza H1N1 virus in mice. AB - BACKGROUND: Understanding the pathogenesis of influenza infection is a key factor leading to the prevention and control of future outbreaks. Pandemic 2009 Influenza H1N1 infection, although frequently mild, led to a severe and fatal form of disease in certain cases that make its virulence nature debatable. Much effort has been made toward explaining the determinants of disease severity; however, no absolute reason has been established. RESULTS: This study presents the heterogeneous virulence of clinically similar strains of pandemic 2009 influenza virus in human alveolar adenocarcinoma cells and mice. The viruses were obtained from patients who were admitted in a local hospital in China with a similar course of infection and recovered. The A/Nanchang/8002/2009 and A/Nanchang/8011/2009 viruses showed efficient replication and high lethality in mice while infection with A/Nanchang/8008/2009 was not lethal with impaired viral replication, minimal pathology and modest proinflammatory activity in lungs. Sequence analysis displayed prominent differences between polymerase subunits (PB2 and PA) of viral genomes that might correlate with their different phenotypic behavior. CONCLUSIONS: The study confirms that biological heterogeneity, linked with the extent of viral replication, exists among pandemic H1N1 strains that may serve as a benchmark for future investigations on influenza pathogenesis. PMID- 22672589 TI - Plasticity of symbiont acquisition throughout the life cycle of the shallow-water tropical lucinid Codakia orbiculata (Mollusca: Bivalvia). AB - In marine invertebrates that acquire their symbionts from the environment, these are generally only taken up during early developmental stages. In the symbiosis between lucinid clams and their intracellular sulfur-oxidizing bacteria, it has been shown that the juveniles acquire their symbionts from an environmental stock of free-living symbiont forms, but it is not known if adult clams are still competent to take up symbiotic bacteria from the environment. In this study, we investigated symbiont acquisition in adult specimens of the lucinid clam Codakia orbiculata, using transmission electron microscopy, fluorescence in situ hybridization, immunohistochemistry and PCR. We show here that adults that had no detectable symbionts after starvation in aquaria for 6 months, rapidly reacquired symbionts within days after being returned to their natural environments in the field. Control specimens that were starved and then exposed to seawater aquaria with sulfide did not reacquire symbionts. This indicates that the reacquisition of symbionts in the starved clams returned to the field was not caused by high division rates of a small pool of remaining symbionts that we were not able to detect with the methods used here. Immunohistochemistry with an antibody against actin, a protein involved in the phagocytosis of intracellular bacteria, showed that actin was expressed at the apical ends of the gill cells that took up symbionts, providing further evidence that the symbionts were acquired from the environment. Interestingly, actin expression was also observed in symbiont containing cells of untreated lucinids freshly collected from the environment, indicating that symbiont acquisition from the environment occurs continuously in these clams throughout their lifetime. PMID- 22672590 TI - Laparoscopic vs open partial nephrectomy for T1 renal tumours: evaluation of long term oncological and functional outcomes in 340 patients. PMID- 22672591 TI - Simplified technique for orbital prosthesis fabrication: a clinical report. AB - Loss of orbital content can cause functional impairment, disfigurement of the face, and psychological distress. Rehabilitation of an orbital defect is a complex task, and if reconstruction by plastic surgery is not possible or not desired by the patient, the defect can be rehabilitated by an orbital prosthesis. The prosthetic rehabilitation in such cases depends on the precisely retained, user-friendly removable maxillofacial prosthesis. Many times, making an impression of the orbital area with an accurate record of surface details can be a difficult procedure. The critical areas are making a facial moulage, mold preparation, and attaching the retention device, particularly when eyeglass frames are used. This case focuses on these hindrance factors. A simple basket was used for the impression tray to obtain the facial moulage. A putty mold was used, and attachment of the prosthesis to a retention device was accomplished with positional distance. This method proves to be an economical and simple way of making an orbital prosthesis. PMID- 22672592 TI - LINE-1 methylation status and its association with tetralogy of fallot in infants. AB - BACKGROUND: Methylation levels of long interspersed nucleotide elements (LINE-1) are representative of genome-wide methylation status and play an important role in maintaining genomic stability and gene expression. To derive insight into the association between genome-wide methylation status and tetralogy of fallot (TOF), we compared the methylation status of LINE-1 element between TOF patients and controls. The methylation of the NKX 2-5, HAND 1, and TBX 20 promoter regions was also evaluated. METHODS: Genomic DNA from right ventricular tissue samples was obtained from 32 patients with TOF and 15 control subjects. Sequenom MassARRAY platform was performed to examine the methylation levels of LINE-1, NKX2-5, HAND1 and TBX20. Mann-Whitney U test was used to compare differences in methylation levels between two groups. RESULTS: The methylation level of LINE-1 was significantly lower in patients with TOF, with a median of 57.95% (interquartile range [IQR]: 56.10%-60.04%), as opposed to 59.70% in controls (IQR: 59.00% 61.30%; P = 0.0021). The highest LINE-1 methylation level was 61.3%. The risk of TOF increased in subjects with the lowest methylation levels (less than or equal to 59.0%; OR = 14.7, 95% CI: 1.8-117.7, P = 0.014) and in those with medium methylation levels (59.0%-61.3%; OR = 2.0, 95% CI: 0.3-14.2, P = 0.65). An ROC curve analysis showed a relatively high accuracy of using the LINE-1 methylation level in predicting the presence of TOF (AUC = 0.78, 95% CI: 0.65-0.91; P = 0.002). The association of the LINE-1 methylation level with TOF was only observed in males (P = 0.006) and not in females (P = 0.25). Neither age nor gender was found to be associated with the LINE-1 methylation level in patients or controls. Higher methylation levels of NKX2-5 and HAND1 and lower methylation levels of TBX20 were also observed in patients with TOF than in controls. No association was found between the methylation levels of NKX2-5, HAND1 and TBX 20 with the LINE-1 methylation level. CONCLUSIONS: Lower LINE-1 methylation levels are associated with increased risk of TOF and may provide important clues for the development of TOF. PMID- 22672593 TI - The role of tissue factor and protease-activated receptor 2 in endometriosis. AB - PROBLEM: Little is known about the roles of TF and PAR-2 in endometriosis. This article investigated the expression of TF and PAR-2 in ectopic and eutopic endometrium with endometriosis and their relationship with the menstrual cycle. METHODS: Ectopic and eutopic endometrium tissues from 42 women with ovarian endometrioma and endometrium tissues from 20 women without endometriosis were obtained. All the samples were assessed for TF and PAR-2 protein location using immunohistochemistry and for relative TF and PAR-2 mRNA expression using real time florescent quantitative polymerase chain reaction (FQ-PCR). RESULTS: Total TF and PAR-2 expression were significantly higher in ectopic and eutopic endometrium of women with endometriosis when compared with controls. Moreover, TF expression in ectopic and eutopic endometrium and PAR-2 expression in ectopic endometrium were significantly increased through the whole menstrual cycle. However, in eutopic endometrium with endometriosis, PAR-2 expression only in secretory phase was higher than its cycle-matched normal controls. There is no such difference in the proliferative phase. CONCLUSION: The abnormal co upregulated expression of TF and PAR-2 in eutopic and ectopic endometrium may affect the development and growth of endometriotic lesions and highlighted the pathologic role of TF and PAR-2 in eutopic endometrium in endometriosis. PMID- 22672594 TI - Nrf2 protects human alveolar epithelial cells against injury induced by influenza A virus. AB - BACKGROUND: Influenza A virus (IAV) infection primarily targets respiratory epithelial cells and produces clinical outcomes ranging from mild upper respiratory infection to severe pneumonia. Recent studies have shown the importance of lung antioxidant defense systems against injury by IAV. Nuclear factor-erythroid 2 related factor 2 (Nrf2) activates the majority of antioxidant genes. METHODS: Alveolar type II (ATII) cells and alveolar macrophages (AM) were isolated from human lungs not suitable for transplantation and donated for medical research. In some studies ATII cells were transdifferentiated to alveolar type I-like (ATI-like) cells. Alveolar epithelial cells were infected with A/PR/8/34 (PR8) virus. We analyzed PR8 virus production, influenza A nucleoprotein levels, ROS generation and expression of antiviral genes. Immunocytofluorescence was used to determine Nrf2 translocation and western blotting to detect Nrf2, HO-1 and caspase 1 and 3 cleavage. We also analyzed ingestion of PR8 virus infected apoptotic ATII cells by AM, cytokine levels by ELISA, glutathione levels, necrosis and apoptosis by TUNEL assay. Moreover, we determined the critical importance of Nrf2 using adenovirus Nrf2 (AdNrf2) or Nrf2 siRNA to overexpress or knockdown Nrf2, respectively. RESULTS: We found that IAV induced oxidative stress, cytotoxicity and apoptosis in ATI-like and ATII cells. We also found that AM can ingest PR8 virus-induced apoptotic ATII cells (efferocytosis) but not viable cells, whereas ATII cells did not ingest these apoptotic cells. PR8 virus increased ROS production, Nrf2, HO-1, Mx1 and OAS1 expression and Nrf2 translocation to the nucleus. Nrf2 knockdown with siRNA sensitized ATI-like cells and ATII cells to injury induced by IAV and overexpression of Nrf2 with AdNrf2 protected these cells. Furthermore, Nrf2 overexpression followed by infection with PR8 virus decreased virus replication, influenza A nucleoprotein expression, antiviral response and oxidative stress. However, AdNrf2 did not increase IFN-lambda1 (IL-29) levels. CONCLUSIONS: Our results indicate that IAV induces alveolar epithelial injury and that Nrf2 protects these cells from the cytopathic effects of IAV likely by increasing the expression of antioxidant genes. Identifying the pathways involved in protecting cells from injury during influenza infection may be particularly important for developing new therapeutic strategies. PMID- 22672595 TI - Is colorectal surveillance indicated in patients with PTEN mutations? AB - AIM: Patients with germline phosphatase and tensin homologue (PTEN) mutations develop hamartomatous lesions in several organs and are at increased risk of various malignancies. We assessed the lifetime risk of benign and malignant gastrointestinal lesions in patients with a proven PTEN mutation. METHOD: Data on gender, mutation, dates of birth, last contact, and diagnosis, location and type of gastrointestinal lesions were collected from nine countries. The lifetime risk of gastrointestinal lesions was calculated by Kaplan-Meier methods. RESULTS: A total of 156 patients (67 men, 43%) from 101 families with a PTEN mutation were included. Patients were born between 1928 and 2008. Benign gastrointestinal polyps were reported in 49 (31%) patients at a mean age of 38 years (range 18-62 years) and were most often hamartomas. Twenty-two (44%) patients had upper as well as lower gastrointestinal lesions, 14 (29%) had only colonic lesions and 13 (27%) had gastrointestinal lesions at unknown sites. The cumulative risk of developing benign gastrointestinal polyps was 70% at age 60. Four patients (two men) developed colorectal carcinoma at 53, 57, 59 and 62 years, respectively. The cumulative risk of developing colorectal carcinoma was 18% at age 60. Except for one carcinoid in the small intestine, no upper gastrointestinal cancers were observed. CONCLUSION: Benign gastrointestinal lesions are common in PTEN mutation carriers, and a three- to four-fold increased lifetime risk of colorectal cancer compared with the general population may exist. Colorectal screening of patients with germline PTEN mutations is recommended, starting at age 40 years. PMID- 22672596 TI - Prevalence of Fabry disease in TIA/stroke cohorts. What defines Fabry disease? PMID- 22672597 TI - Context matters...more than ever. PMID- 22672598 TI - Interventions for improving coordination of reach to grasp following stroke: a systematic review. AB - BACKGROUND: Stroke is associated with disruption to efficient and accurate reach to grasp function. Information about treatments for upper limb coordination deficits and their effectiveness may contribute to improved recovery of upper limb function after stroke. AIMS: To identify all existing interventions targeted at coordination of arm and hand segments for reach to grasp following stroke. To determine the effectiveness of current treatments for improving coordination of reach to grasp after stroke. SEARCH STRATEGY: The search included The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); MEDLINE; EMBASE; CINAHL; AMED; ProQuest Dissertations and Theses (International) and ISI Proceedings (Conference) databases. A grey literature search included Mednar, Dissertation International, Conference Proceedings, National Institute of Health Clinical Trials and the National Institute of Clinical Studies. We also explored Physiotherapy Evidence Database, Chartered Society of Physiotherapy Research and REHABDATA therapy databases. Finally, the reference lists of identified articles were examined for additional studies. The search spanned from 1950 to April 2010 and was limited to English language papers only. METHODS OF THE REVIEW: Studies were included with a specific design objective related to coordination of the hand and arm during reach to grasp and involving participants with a clinical diagnosis of stroke. The review was inclusive with regard to study design. To determine effectiveness of interventions we analysed studies with coordination measures that exist within impairment measurement scales or specific kinematic measures of coordination. The methodological quality of the studies was assessed by two independent authors using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Comparable Cohort/Case Control and the JBI Critical Appraisal Checklist for Experimental Studies together with additional questions from Downs and Black. Two review authors independently extracted data from the studies using standardised JBI-MAStARI data extraction forms. Pooling of results was not appropriate so the findings were summarised in tables and in narrative form. RESULTS: One randomised controlled trial, two case-control studies and four experimental studies without controls were included in this review. The review has identified three categories of potential intervention for improving hand and arm coordination after stroke; functional therapy, biofeedback or electrical stimulation and robot or computerised training. In view of the limited availability of good quality evidence and lack of empirical data, this review does not draw a definitive conclusion for the second question regarding the effectiveness of interventions aimed at improving hand and arm coordination after stroke. Improvements in hand and arm coordination during reach to grasp were reported in four studies, whereas one study found no benefit. Two studies did not report specific effects of interventions for hand and arm coordination after stroke. CONCLUSIONS: IMPLICATIONS FOR PRACTICE: There is currently insufficient evidence to provide strong recommendations about the effect of interventions for improving hand and arm coordination during reach to grasp after stroke. IMPLICATIONS FOR RESEARCH: Randomised controlled trials of sufficient power with standardised outcome measures are needed to enable meta-analysis comparison in the future. Such studies should include both functional performance and detailed kinematic measures of hand and arm coordination. PMID- 22672599 TI - Size matters: a meta-analysis on the impact of hospital size on patient mortality. AB - OBJECTIVE: This paper seeks to understand the relationship between hospital size and patient mortality. Patient mortality has been used by several studies in the health services research field as a proxy for measuring healthcare quality. RESEARCH METHODS: A systematic review is conducted to identify studies that investigate the impact of hospital size on patient mortality. Using the findings of 21 effect sizes from 10 eligible studies, a meta-analysis is performed using a random effects model. Subgroup analyses using three factors--the measure used for hospital size, type of mortality measure used and whether mortality was adjusted or unadjusted--were utilised to investigate their moderating influence on the study's primary relationship. RESULTS: Results from this analysis indicate that big hospitals have lower odds of patient mortality versus small hospitals. Specifically, the probability of patient mortality in a big hospital, in reference to a small hospital, is 11% less. Subgroup analyses show that studies with unadjusted mortality rates have an even lower overall odds ratio of mortality versus studies with adjusted mortality rates. CONCLUSIONS: Aside from some limitations in data reporting, the findings of this paper support theoretical notions that big hospitals have lower mortality rates than small hospitals. Guidelines for better data reporting and future research are provided to further explore the phenomenon. Policy implications of this paper's findings are underscored and a sense of urgency is called for in an effort to help improve the state of a healthcare system that struggles with advancing healthcare quality. PMID- 22672600 TI - Early laparoscopic cholecystectomy in a district general hospital: is it safe and feasible? AB - BACKGROUND: Early laparoscopic cholecystectomy (ELC) is becoming the accepted treatment for the management of acute gallstone disease in specialist centres. It has also been achieved safely in the district general hospital (DGH) setting. We audited the management of acute gallstone disease in our DGH and set about to see if we could implement ELC safely and effectively. PATIENTS AND METHODS: A retrospective audit of 2 years of practice was performed using our hospital computerised systems. Following this, departmental education regarding the benefits of early cholecystectomy was widely disseminated. Management guidelines were altered to promote and consider ELC for all suitable patients. A prospective audit of practice was then performed for 6 months. RESULTS: The first cycle revealed that only 10.42% of emergency patients admitted with gallstone-related disease had ELC. In the second cycle, 63 patients were admitted with acute gallstone disease. Three died from acute pancreatitis. Twenty-one (58%) of the 36, who were deemed suitable, had ELC. Fifteen (42%) had planned delayed laparoscopic cholecystectomy (DLC), with six (40%) being readmitted whilst waiting for their elective surgery (all undergoing ELC during their readmission). Conversion rates were similar between all groups. One of the patients having DLC had a bile leak, which settled following Endoscopic Retrograde Cholangiopancreatography and stent. CONCLUSION: We were able to increase ELC rates following the implementation of necessary changes. There did not appear to be any difference in conversion or morbidity rates between ELC and DLC. We conclude ELC is safe and feasible in the DGH setting. PMID- 22672601 TI - Evidence-based practice in a multiprofessional context. AB - BACKGROUND: Healthcare today is a complex system with increasing needs of specific knowledge of evaluation of research and implementation into clinical practice. A critical issue is that we all apply evidence-based practice (EBP) with standardised methods and continuing and systematic improvements. EBP includes both scientific and critical assessed experience-based knowledge. For the individual, this means applying evidence-based knowledge to a specific situation, and for the organisation, it means catering for a systematic critical review and evaluation and compiling research into guidelines and programmes. In 2009, the County Council of Jonkoping had approximately 335,000 inhabitants and the healthcare organisation had more than 10,000 employees. As the County Council actively promotes clinical improvement, it is interesting to explore how healthcare employees think about and act upon EBP. The aim of this survey was therefore to describe factors that facilitate or hinder the application of EBP in the clinical context. METHOD: A quantitative study was performed with a questionnaire to healthcare staff employed in the County Council of Jonkoping in 2009. The questionnaire consisted of questions concerning which factors are experienced to affect the development of evidence-based healthcare. There were 59 open and closed questions, divided into the following areas: * Sources of knowledge used in practice * Barriers to finding and evaluating research reports and guidelines * Barriers to changing practice on the basis of best evidence * Facilitating factors for changing practice on the basis of best evidence * Experience in finding, evaluating and using different sources of evidence. The participants were selected using the county council's staff database and included medical, caring and rehabilitative staff within hospitals, primary care, dentistry and laboratory medicine. The inclusion criteria were permanent employment and clinical work. Invitations were sent to 5787 persons to participate in the study and 1445 persons answered the questionnaire. RESULTS: Knowledge used in daily clinical practice was mainly based on information about the patient, personal experience and local guidelines. Twenty per cent answered that they worked 'in the way they always had', and 11% responded that they used evidence from research as a basis for change. The participants experienced that EBP was not used enough in clinical healthcare and explained this with practical and structural barriers, which they thought should be better monitored by the organisation and directors. CONCLUSION: Overall, the results indicate that the scientific evidence for healthcare is not used sufficiently as a base for decisions in daily practice as well as for changing practice. This is more prominent among assistant staff. As a consequence, this might affect the care of the patients in a negative way. Increased awareness of EBP and a stronger evidence-based approach are keys in the ongoing improvement work in the county. Local guidelines seem to be a way to implement knowledge. But, as the arena of activities is complex and the employees have diverse education levels, different strategies to facilitate and promote EBP are necessary. PMID- 22672602 TI - Systematic review on the relationship between the nursing shortage and job satisfaction, stress and burnout levels among nurses in oncology/haematology settings. AB - AIM: To establish the best available evidence regarding the relationship between the nursing shortage and nurses' job satisfaction, stress and burnout levels in oncology/haematology settings. METHODS: Electronic databases (CINAHL, Medline, Scopus, ScienceDirect, PsycInfo, PsycArticles, Web of Science, The Cochrane Library, Proquest and Mednar) were searched using a three-step strategy in order to identify published and unpublished studies conducted between 1990 and 2010. Grey literature was excluded in the review. The identified studies were evaluated using standardised critical appraisal instruments from the Joanna Briggs Institute-Meta Analysis of Statistics Assessment and Review Instrument (JBI MAStARI). A total of seven descriptive and descriptive-correlational studies published in English were included and data were presented in a narrative summary. RESULTS: Findings revealed a positive bidirectional relationship between the nursing shortage and oncology registered nurses' (RNs') job dissatisfaction, stress and burnout. The extent of the job dissatisfaction, stress and burnout experienced by the oncology RNs and their perception of staffing inadequacy differed according to their demography and work settings. Particularly, nurses who had higher qualifications and positions, who worked full-time and who worked in inpatient settings and non-Magnet hospitals were more likely to attribute staffing inadequacy as one of the main contributing factors for their job dissatisfaction, stress and burnout. This led to a rise in the number of oncology RNs leaving the speciality. CONCLUSION: Within the constraints of the study and the few quality papers available, it appears that oncology RNs who worked in substandard staffing units often express job dissatisfaction, stress and burnout, which prompt them to seek new employment out of the oncology specialty. This entails a pressing need for organisations to ensure sufficient staffing in oncology/haematology settings, in order to ensure that quality patient care is provided. Limited studies that examine the relationship between the nursing shortage and oncology RNs' stress and burnout have been conducted. Also, no studies in the Asian context have previously been conducted. IMPLICATIONS FOR PRACTICE: Organizations need to customize their strategies for the recruitment and retention of oncology nurses. The strategies should take into consideration the specific demographic characteristics of oncology nurses or those of work settings that are experiencing staffing inadequacy and negative nursing outcomes. The strategies should also aim to replicate features of other institutions that are attractive to oncology nurses, and also include training that help oncology nurses better manage their emotions. IMPLICATIONS FOR RESEARCH: Future research needs to examine the relationship between the nursing shortage and oncology nurses' job satisfaction, stress and burnout in bone marrow transplant units, paediatric oncology settings and Asian oncology settings. The characteristics of oncology nurses or workplaces that are more likely to experience negative nursing outcomes due the nursing shortage should also be identified. PMID- 22672603 TI - Document analysis using an aggregative and iterative process. AB - This paper is a descriptive commentary concerning the use of document analysis in qualitative research concerned with developing an understanding of the role of child and adolescent mental health nursing in an inpatient. The document analysis was undertaken using thematic analysis with both an iterative process (Attride Stirling) and an aggregative process, the Joanna Briggs Institute Thematic Analysis Program (TAP). After the initial iterative process the data were entered into an online software program, TAP, for aggregation and further analysis. The TAP software consisted of a three-step approach in the analysis of data extraction of illustrations, aggregation to categories and synthesis of categories into themes. A TAP chart was generated displaying the connections between the illustrations, categories and themes. The advantage and limitations of utilising the TAP software compared with Computer Assisted Qualitative Data Analysis Software were discussed. The program afforded direct involvement by the researcher in the cognitive process of the analysis; rather than just the technical process. A limitation of the program would be the volume of the data if the research involved a vast amount of data. The TAP program was a clearly defined three-step software program that was appropriate for the documents analysis for the research. The program would have a wide application for facilitating the thematic analysis of documents, although the program is suitable for smaller amounts of data. PMID- 22672604 TI - Reducing inequality in health through evidence-based clinical guidance: is it feasible? The New Zealand experience. AB - Evidence-based guidance and guidelines need to include the voices of the most disadvantaged groups in society; doing so is a significant challenge, but one which is critical to a responsive and healthcare system. Addressing ethnic disparity (and other types of disparity) in health via evidence-based guidance is likely to be less effective if approaches are singular and do not address issues of participation by those groups who have the greatest stake in improved health outcomes. This paper presents a multifaceted framework, which has been developed in New Zealand to ensure health inequalities experienced by Maori (the indigenous population within New Zealand) are addressed when developing evidence-based guidance. The framework has two overarching goals. These are: (i) to ensure the explicit identification of Maori health needs occurs during each formal stage of guideline development; and (ii) to ensure there is full Maori participation in the guidance development process. The steps to achieving these two goals are described in detail. The framework presented is evolving and intended to be flexible dependent upon healthcare environments and resourcing. This paper is intended to provide some focus and discussion for the role of evidence-based guidance in both addressing and entrenching health inequalities in vulnerable groups. PMID- 22672605 TI - Evidence-based abstracts: what research summaries should contain to support evidence-based medicine. AB - The practice of evidence-based medicine involves the integration of individual clinical expertise with the best available external clinical evidence from the systematic retrieval of the most current literature. Clinicians need to conduct a critical appraisal of the medical articles they access. However, clinicians in developing countries usually lack access to the best resources for evidence-based practice (EBP). The abstracts of 100 of the most recently published randomised controlled trials were used in the present study. These abstracts were critically appraised using a new questionnaire. Questions 1 to 8 were answerable by 38%, 26%, 52%, 23%, 12%, 53%, 36% and 12%, respectively, of the examined summaries. EBP requires better access to medical resources. Therefore, the summaries of relevant studies should be complete and self-sufficient to support EBP. This means a research summary should adequately report the findings of a clinical trial without needing to access the full text. PMID- 22672609 TI - The "east-west" advancement flap for nasal defects: reexamined and extended. PMID- 22672610 TI - Increasing alcohol use disorders among mid-life Australians: time for a new focus? PMID- 22672611 TI - Radiographic and clinical outcomes of implants placed in ridge preserved sites: a 12-month post-loading follow-up. AB - OBJECTIVE: The aim of this clinical study was to evaluate the interproximal radiographic bone levels and the survival/success rate of dental implants placed in alveolar ridges previously preserved with a synthetic bone substitute or a bovine xenograft. MATERIAL AND METHODS: Alveolar ridge preservation was performed in 27 patients who were randomly assigned in two groups. In the test group (n = 14), the extraction socket was treated with a synthetic bone graft Straumann Bone Ceramic; SBC and a collagen barrier, whereas in the control group (n = 13) a deproteinized bovine bone mineral (DBBM) and the same collagen barrier were used. After 8 months of healing, titanium dental implants with a hydrophilic surface were placed in the preserved ridges. During surgery, 9/13 implants in the SBC group and 8/12 implants in the DBBM group presented with either dehiscence or fenestration defects and required additional bone augmentation. The implants were loaded at 4 months following placement and were followed up for 1 year post loading. Interproximal radiographic bone levels were evaluated in standardized periapical radiographs at loading and 1 year post-loading. Probing pocket depth, gingival recession and bleeding upon probing were recorded at implants and neighbouring teeth. The success rate of the implants was evaluated according to criteria set by Albrektsson et al. (1986). RESULTS: The survival rate of the implants in both groups was 100% at 1-year post-loading. No statistically significant differences in any of the clinical and radiographic measurements were detected between the two groups (P < 0.05). The success rate of the implants was 84.6% (11/13) in the SBC group and 83.3% (10/12) in the DBBM group. CONCLUSION: Equivalent success and survival rates (as well as similar radiographic changes) of dental implants placed in alveolar ridges previously preserved with SBC or DBBM should be anticipated. PMID- 22672612 TI - Neuropathologic analysis of Lewy-related alpha-synucleinopathy in olfactory mucosa. AB - We analyzed the incidence and extent of Lewy-related alpha-synucleinopathy (LBAS) in the olfactory mucosa, as well as the central and peripheral nervous systems of consecutive autopsy cases from a general geriatric hospital. The brain and olfactory mucosa were immunohistochemically examined using antibodies raised against phosphorylated alpha-synuclein. Thirty-nine out of 105 patients (37.1%) showed LBAS in the central or peripheral nervous systems. Seven patients presented LBAS (Lewy neurites) in the olfactory lamina propria mucosa. One out of the seven cases also showed a Lewy neurite in a bundle of axons in the cribriform plate, but alpha-synuclein deposits were not detected in the olfactory receptor neurons. In particular, high incidence of alpha-synuclein immunopositive LBAS in the olfactory mucosa was present in the individuals with clinically as well as neuropathologically confirmed Parkinson's disease and dementia with Lewy bodies (6/8 cases, 75%). However, this pathologic alteration was rare in the cases with incidental or subclinical Lewy body diseases (LBD) (one out of 31 cases, 3.2%). In the olfactory bulb, the LBAS was usually present in the glomeruli and granular cells of most symptomatic and asymptomatic cases with LBD. Our studies further confirmed importance of the olfactory entry zone in propagation of LBAS in the human aging nervous system. PMID- 22672613 TI - Prevalence of restless legs syndrome in Japanese patients with chronic liver disease. AB - AIM: Sleep disturbance is a major complication in patients with chronic liver disease, but causes are unclear. The aim of this study was to clarify the prevalence of restless legs syndrome (RLS) in Japanese chronic liver disease patients and investigate the influence on sleep and quality of life. METHODS: The study included 149 consecutive outpatients with chronic liver disease at Nagasaki University Hospital between September 2008 and March 2010. The presence of RLS was evaluated by a written survey using the questionnaire for the epidemiological surveillance of the international RLS research group in 2003. In addition, 89 cases, including all RLS patients, were evaluated for sleep quality and health-related quality of life. Sleep quality was evaluated by using the Japanese version of the Pittsburgh Sleep Quality Index (PSQI), and health-related quality of life was evaluated by the Japanese SF-36 Health Survey. RESULT: Twenty-five of the 149 patients (16.8%) fulfilled the diagnostic criteria for RLS. The median global PSQI score of the RLS group was significantly higher than the non-RLS group (9 vs 5, P < 0.01). The number of poor sleepers (global PSQI score, >5) in the RLS group was significantly higher than in the non-RLS group (P < 0.05). In SF-36, the mental component summary score of the RLS group was 43.8 +/- 10.8, which was significantly lower than the non-RSL group (49.8 +/- 10.5; P < 0.05). CONCLUSION: This is the first report that clarifies the prevalence of RLS in Japanese chronic liver disease patients. RLS worsens quality of sleep and life in chronic liver disease patients. PMID- 22672614 TI - Thalassemia major phenotypes secondary to the association of beta 5'UTR +20(C -> T) allele with beta 39(C -> T). PMID- 22672615 TI - Dietary restriction attenuates age-associated muscle atrophy by lowering oxidative stress in mice even in complete absence of CuZnSOD. AB - Age-related loss of muscle mass and function, sarcopenia, has a major impact on the quality of life in the elderly. Among the proposed causes of sarcopenia are mitochondrial dysfunction and accumulated oxidative damage during aging. Dietary restriction (DR), a robust dietary intervention that extends lifespan and modulates age-related pathology in a variety of species, has been shown to protect from sarcopenia in rodents. Although the mechanism(s) by which DR modulates aging are still not defined, one potential mechanism is through modulation of oxidative stress and mitochondrial dysfunction. To directly test the protective effect of DR against oxidative stress-induced muscle atrophy in vivo, we subjected mice lacking a key antioxidant enzyme, CuZnSOD (Sod1) to DR (60% of ad libitum fed diet). We have previously shown that the Sod1(-/-) mice exhibit an acceleration of sarcopenia associated with high oxidative stress, mitochondrial dysfunction, and severe neuromuscular innervation defects. Despite the dramatic atrophy phenotype in the Sod1(-/-) mice, DR led to a reversal or attenuation of reduced muscle function, loss of innervation, and muscle atrophy in these mice. DR improves mitochondrial function as evidenced by enhanced Ca2+ regulation and reduction of mitochondrial reactive oxygen species (ROS). Furthermore, we show upregulation of SIRT3 and MnSOD in DR animals, consistent with reduced mitochondrial oxidative stress and reduced oxidative damage in muscle tissue measured as F2-isoprostanes. Collectively, our results demonstrate that DR is a powerful mediator of mitochondrial function, mitochondrial ROS production, and oxidative damage, providing a solid protection against oxidative stress-induced neuromuscular defects and muscle atrophy in vivo even under conditions of high oxidative stress. PMID- 22672616 TI - Differential roles of galanin on mechanical and cooling responses at the primary afferent nociceptor. AB - BACKGROUND: Galanin is expressed in a small percentage of intact small diameter sensory neurons of the dorsal root ganglia and in the afferent terminals of the superficial lamina of the dorsal horn of the spinal cord. The neuropeptide modulates nociception demonstrating dose-dependent pro- and anti-nociceptive actions in the naive animal. Galanin also plays an important role in chronic pain, with the anti-nociceptive actions enhanced in rodent neuropathic pain models. In this study we compared the role played by galanin and its receptors in mechanical and cold allodynia by identifying individual rat C-fibre nociceptors and characterising their responses to mechanical or acetone stimulation. RESULTS: Mechanically evoked responses in C-fibre nociceptors from naive rats were sensitised after close intra-arterial infusion of galanin or Gal2-11 (a galanin receptor-2/3 agonist) confirming previous data that galanin modulates nociception via activation of GalR2. In contrast, the same dose and route of administration of galanin, but not Gal2-11, inhibited acetone and menthol cooling evoked responses, demonstrating that this inhibitory mechanism is not mediated by activation of GalR2. We then used the partial saphenous nerve ligation injury model of neuropathic pain (PSNI) and the complete Freund's adjuvant model of inflammation in the rat and demonstrated that close intra-arterial infusion of galanin, but not Gal2-11, reduced cooling evoked nociceptor activity and cooling allodynia in both paradigms, whilst galanin and Gal2-11 both decreased mechanical activation thresholds. A previously described transgenic mouse line which inducibly over-expresses galanin (Gal-OE) after nerve injury was then used to investigate whether manipulating the levels of endogenous galanin also modulates cooling evoked nociceptive behaviours after PSNI. Acetone withdrawal behaviours in naive mice showed no differences between Gal-OE and wildtype (WT) mice. 7-days after PSNI Gal-OE mice demonstrated a significant reduction in the duration of acetone-induced nociceptive behaviours compared to WT mice. CONCLUSIONS: These data identify a novel galaninergic mechanism that inhibits cooling evoked neuronal activity and nociceptive behaviours via a putative GalR1 mode of action that would also be consistent with a TRP channel-dependent mechanism. PMID- 22672617 TI - Characterization of placental transfer of polychlorinated dibenzo-p-dioxins, dibenzofurans and polychlorinated biphenyls in normal pregnancy. AB - AIM: Prenatal exposure to dioxins may result in many adverse health effects. However, the mechanisms by which dioxins are transferred from mother to fetus through the placenta are not well understood. The aim of this study was to investigate the differences in dioxin concentrations between maternal blood, the placenta, and cord blood in normal pregnant women, and to identify which individual congeners of these compounds are transferred from mother to fetus through the placenta. MATERIAL AND METHODS: Samples were collected from 19 pregnant Japanese women. Specific congeners of seven polychlorinated dibenzo-p dioxins (PCDDs), 10 polychlorinated dibenzofurans (PCDFs), and four non-ortho polychlorinated biphenyls (PCBs) were analyzed. RESULTS: The TEQ concentrations of PCDDs, PCDFs, and non-ortho PCBs were 8.03, 3.39, and 3.95 pg TEQ/g lipid, respectively, in the maternal blood; 8.78, 3.61, and 0.87 pg TEQ/g lipid in the placenta; and 4.33, 1.25, 1.08 pg TEQ/g lipid in the cord blood. Among specific congeners, 1,2,3,7,8-PentaCDD and 2,3,4,7,8-PentaCDF exhibited a placenta to maternal blood ratio greater than 1.0, while OctaCDD exhibited the greatest cord blood to placenta ratio. The cord blood to maternal blood ratio of total PCDDs was significantly higher than that of total PCDFs and total non-ortho PCBs. CONCLUSION: The dioxin concentration in cord blood was approximately half of the amount in maternal blood, despite congeners showing a high toxic equivalency factor accumulating in the placenta. PCDDs were transferred more readily than PCDFs and non-ortho PCBs from maternal blood to the fetus through the placenta. PMID- 22672619 TI - DREB1A promotes root development in deep soil layers and increases water extraction under water stress in groundnut. AB - Water deficit is a major yield-limiting factor for many crops, and improving the root system has been proposed as a promising breeding strategy, although not in groundnut (Arachis hypogaea L.). The present work was carried out mainly to assess how root traits are influenced under water stress in groundnut, whether transgenics can alter root traits, and whether putative changes lead to water extraction differences. Several transgenic events, transformed with DREB1A driven by the rd29 promoter, along with wild-type JL24, were tested in a lysimeter system that mimics field conditions under both water stress (WS) and well-watered (WW) conditions. The WS treatment increased the maximum rooting depth, although the increase was limited to about 20% in JL24, compared to 50% in RD11. The root dry weight followed a similar trend. Consequently, the root dry weight and length density of transgenics was higher in layers below 100-cm depth (Exp. 1) and below 30 cm (Exp. 2). The root diameter was unchanged under WS treatment, except a slight increase in the 60-90-cm layer. The root diameter increased below 60 cm in both treatments. In the WW treatment, total water extraction of RD33 was higher than in JL24 and other transgenic events, and somewhat lower in RD11 than in JL24. In the WS treatment, water extraction of RD2, RD11 and RD33 was higher than in JL24. These water extraction differences were mostly apparent in the initial 21 days after treatment imposition and were well related to root length density in the 30-60-cm layer (R(2) = 0.68), but not to average root length density. In conclusion, water stress promotes rooting growth more strongly in transgenic events than in the wild type, especially in deep soil layers, and this leads to increased water extraction. This opens an avenue for tapping these characteristics toward the improvement of drought adaptation in deep soil conditions, and toward a better understanding of genes involved in rooting in groundnut. PMID- 22672618 TI - Decreased expression of extracellular matrix proteins and trophic factors in the amygdala complex of depressed mice after chronic immobilization stress. AB - BACKGROUND: The amygdala plays an essential role in controlling emotional behaviors and has numerous connections to other brain regions. The functional role of the amygdala has been highlighted by various studies of stress-induced behavioral changes. Here we investigated gene expression changes in the amygdala in the chronic immobilization stress (CIS)-induced depression model. RESULTS: Eight genes were decreased in the amygdala of CIS mice, including genes for neurotrophic factors and extracellular matrix proteins. Among these, osteoglycin, fibromodulin, insulin-like growth factor 2 (Igf2), and insulin-like growth factor binding protein 2 (Igfbp2) were further analyzed for histological expression changes. The expression of osteoglycin and fibromodulin simultaneously decreased in the medial, basolateral, and central amygdala regions. However, Igf2 and Igfbp2 decreased specifically in the central nucleus of the amygdala. Interestingly, this decrease was found only in the amygdala of mice showing higher immobility, but not in mice displaying lower immobility, although the CIS regimen was the same for both groups. CONCLUSIONS: These results suggest that the responsiveness of the amygdala may play a role in the sensitivity of CIS-induced behavioral changes in mice. PMID- 22672620 TI - Roadmap for a participatory research-practice partnership to implement evidence. AB - BACKGROUND: Our research team has undertaken implementation of evidence in the form of practice guideline recommendations for populations in hospital, community, and long-term care settings with diverse provider and patient populations (people with chronic wounds, e.g., pressure and leg ulcers, heart failure, stroke, diabetes, palliative care, cancer, and maternity care). Translating evidence into clinical practice at the point of care is a complex and often overwhelming challenge for the health system as well as for individual practitioners. PURPOSE: To ensure that best available evidence is integrated into practice, "local evidence" needs to be generated and this process accomplishes a number of things: it focuses all involved on the "same page," identifies important facilitating factors as well as barriers, provides empirical support for planning, and in itself is a key aspect of implementation. In doing this work, we developed a roadmap, the Queen's University Research Roadmap for Knowledge Implementation (QuRKI) that outlines three major phases of linked research and implementation activity: (1) issue identification/clarification; (2) solution building; and (3) implementation, evaluation, and nurturing the change. In this paper, we describe our practical experience as researchers working at point-of-care and how research can be used to facilitate the implementation of evidence. An exemplar is used to illustrate the fluid interplay of research and implementation activities and present the range of supporting research. IMPLICATIONS: QuRKI serves as a guide for researchers in the formation of a strategic alliance with the practice community for undertaking evidence-informed reorganization of care. Using this collaborative approach, researchers play an integral role in focusing on, and using evidence during all discussions. We welcome further evaluation of its usefulness in the field. PMID- 22672622 TI - Testing postural control among various osteoporotic patient groups: a literature review. AB - AIM: Osteoporosis can cause vertebral fractures, which might lead to a flexed posture, impaired postural control and consequently increased fall risk. Therefore, the aim of the present review was to examine whether postural control of patients with osteoporosis, vertebral fractures, thoracic kyphosis and flexed posture is affected. Furthermore, instruments measuring postural control were evaluated and examined for sensitivity and easy clinical use. METHODS: Until February 2011, electronic databases were systematically searched for cross sectional studies. Methodological quality was assessed with a modified Downs & Black scale. RESULTS: Of the 518 found studies, 18 studies were included. Postural control was generally affected for patients with vertebral fractures, thoracic kyphosis and flexed posture. Patients with osteoporosis had impaired postural control when assessed with computerized instruments. Easy performance based tests did not show any impairments. CONCLUSIONS: There is evidence for an impaired postural control in all patient groups included. Impaired postural control is an important risk factor for falls. Functional performance tests are not sensitive and specific enough to detect affected postural control in patients with osteoporosis. To detect impaired postural control among osteoporotic patients and to obtain more insight into the underlying mechanisms of postural control, computerized instruments are recommended, such as easy-to-use ambulant motion-sensing (accelerometry) technology. PMID- 22672623 TI - RAD sequencing yields a high success rate for westslope cutthroat and rainbow trout species-diagnostic SNP assays. AB - Hybridization with introduced rainbow trout threatens most native westslope cutthroat trout populations. Understanding the genetic effects of hybridization and introgression requires a large set of high-throughput, diagnostic genetic markers to inform conservation and management. Recently, we identified several thousand candidate single-nucleotide polymorphism (SNP) markers based on RAD sequencing of 11 westslope cutthroat trout and 13 rainbow trout individuals. Here, we used flanking sequence for 56 of these candidate SNP markers to design high-throughput genotyping assays. We validated the assays on a total of 92 individuals from 22 populations and seven hatchery strains. Forty-six assays (82%) amplified consistently and allowed easy identification of westslope cutthroat and rainbow trout alleles as well as heterozygote controls. The 46 SNPs will provide high power for early detection of population admixture and improved identification of hybrid and nonhybridized individuals. This technique shows promise as a very low-cost, reliable and relatively rapid method for developing and testing SNP markers for nonmodel organisms with limited genomic resources. PMID- 22672621 TI - Prediction and course of symptoms and lung function around an exacerbation in chronic obstructive pulmonary disease. AB - BACKGROUND: Frequent exacerbations induce a high burden to Chronic Obstructive Pulmonary Disease (COPD). We investigated the course of exacerbations in the published COSMIC study that investigated the effects of 1-year withdrawal of fluticasone after a 3-month run-in treatment period with salmeterol/fluticasone in patients with COPD. METHODS: In 373 patients, we evaluated diary cards for symptoms, Peak Expiratory Flow (PEF), and salbutamol use and assessed their course during exacerbations. RESULTS: There were 492 exacerbations in 224 patients. The level of symptoms of cough, sputum, dyspnea and nocturnal awakening steadily increased from 2 weeks prior to exacerbation, with a sharp rise during the last week. Symptoms of cough, sputum, and dyspnea reverted to baseline values at different rates (after 4, 4, and 7 weeks respectively), whereas symptoms of nocturnal awakening were still increased after eight weeks. The course of symptoms was similar around a first and second exacerbation. Increases in symptoms and salbutamol use and decreases in PEF were associated with a higher risk to develop an exacerbation, but with moderate predictive values, the areas under the receiver operating curves ranging from 0.63 to 0.70. CONCLUSIONS: Exacerbations of COPD are associated with increased symptoms that persist for weeks and the course is very similar between a first and second exacerbation. COPD exacerbations are preceded by increased symptoms and salbutamol use and lower PEF, yet predictive values are too low to warrant daily use in clinical practice. PMID- 22672624 TI - A new surgical template with a handpiece positioner for use during flapless placement of four dental implants to retain a mandibular overdenture. AB - This article describes the fabrication of a new and inexpensive surgical template from a radiographic template for flapless placement of dental implants to retain a mandibular overdenture. A radiographic template with radiopaque metal plate markers is constructed and used as a guide for achieving three-dimensional evaluation of bone using computed tomography (CT). The potential position and angulation of the implants are measured relative to the metal plates using the CT data. The radiographic template is converted into a surgical template by attaching rigid metal rods that guide the handpiece precisely during subsequent drilling procedures. PMID- 22672625 TI - Human gene correlation analysis (HGCA): a tool for the identification of transcriptionally co-expressed genes. AB - BACKGROUND: Bioinformatics and high-throughput technologies such as microarray studies allow the measure of the expression levels of large numbers of genes simultaneously, thus helping us to understand the molecular mechanisms of various biological processes in a cell. FINDINGS: We calculate the Pearson Correlation Coefficient (r-value) between probe set signal values from Affymetrix Human Genome Microarray samples and cluster the human genes according to the r-value correlation matrix using the Neighbour Joining (NJ) clustering method. A hyper geometric distribution is applied on the text annotations of the probe sets to quantify the term overrepresentations. The aim of the tool is the identification of closely correlated genes for a given gene of interest and/or the prediction of its biological function, which is based on the annotations of the respective gene cluster. CONCLUSION: Human Gene Correlation Analysis (HGCA) is a tool to classify human genes according to their coexpression levels and to identify overrepresented annotation terms in correlated gene groups. It is available at: http://biobank-informatics.bioacademy.gr/coexpression/. PMID- 22672626 TI - Long-term outcome of the use of intravesical botulinum toxin for the treatment of overactive bladder (OAB). PMID- 22672627 TI - Use of service data to inform pediatric HIV-free survival following prevention of mother-to-child transmission programs in rural Malawi. AB - BACKGROUND: Recent years have seen rapid and significant progress in science and implementation of programs to prevent mother-to-child transmission of HIV. Programs that support PMTCT routinely monitor service provision but very few have measured their effectiveness. The objective of the study was to use service data to inform HIV-free survival among HIV exposed children that received antiretroviral drugs to prevent mother-to-child transmission (PMTCT) of HIV. The study was conducted in two rural districts in Malawi with support from FHI 360. METHODS: A descriptive observational study of PMTCT outcomes was conducted between June 2005 and June 2009. The dataset included patient-level data of all pregnant women 1) that tested HIV-positive, 2) that were dispensed with antiretroviral prophylaxis, and 3) whose addresses were available for home visits. The data were matched to each woman's corresponding antenatal clinic data from home visit registers. RESULTS: Out of 438 children whose home addresses were available, 33 (8%) were lost to follow-up, 35 (8%) were alive but not tested for HIV by the time home visit was conducted, and 52 (12%) were confirmed deceased. A total of 318 children were alive at the time of the home visit and had an HIV antibody test done at median age 15 months. The resulting estimated 24-month probability of HIV-free survival over all children was 78%. Among children who did not receive nevirapine, the estimated 24-month probability of HIV-free survival was 61%, and among those who did receive NVP syrup the estimate was 82%. CONCLUSIONS: When mothers and newborns received nevirapine, the estimated 24 month probability of HIV-free survival among children was high at 82% (CI: 54% to 99%). However this conclusion should be interpreted cautiously 1) due to the wide confidence interval; and 2) because the confidence interval range includes 55%, which is the natural HIV-free survival rate in the absence of a PMTCT intervention. This analysis highlighted the need of quality data and well structured home visits to assess PMTCT effectiveness. PMID- 22672629 TI - The WIMAT colonoscopy suitcase model: a novel porcine polypectomy trainer. AB - AIM: Simulation allows the acquisition of complex skills within a safe environment. Endoscopic polypectomy has a long learning curve. Our novel polypectomy simulator may be a useful adjunct for training. The aim of this study was to assess its content validity. METHOD: The Welsh Institute for Minimal Access Therapy (WIMAT) endoscopy suitcase was designed to simulate colonic polypectomy. Participants from regional and national courses were recruited into the study. Each undertook a standardized simulated polypectomy and completed a seven-point Likert scale questionnaire examining its realism. RESULTS: In all, 17 participants completed the questionnaire: 15 (88.2%) gastroenterologists, one (5.9%) colorectal surgeon and one (5.9%) experienced endoscopic nurse specialist. Of the gastroenterologists, seven (46.7%) were consultants and eight (53.3%) were senior trainees or Post CCT (Certificate of Completion of Training) fellows. The mean number of real-life polypectomies performed by the cohort was 156 (95% CI 35 355). The highest scores were for 'mucosal realism' (median score 6.0, P=0.001), 'endoscopic snare control' (median score 6.0, P=0.001), 'handling the polyp' (median score 6.0, P=0.001) and 'raising mucosa' (median score 6.0, P<0.001). Of the 15 parameters examined only three were not statistically significant in favour of the simulator. These were 'anatomical realism of sessile polyps', 'resistance of scope movement' and 'paradoxical motion'. The overall score for the simulation was 6.0 (P < 0.001). There was no significant difference between the level of difficulty of the simulator compared with real life (median score 4.0, P = 0.559). CONCLUSION: The WIMAT colonoscopy suitcase model has excellent content validity for several parameters. This may have potential applications in medical training and assessment. PMID- 22672628 TI - Cyclic changes in the level of the innate immune molecule, surfactant protein-a, and cytokines in vaginal fluid. AB - PROBLEM: Our knowledge of the innate host defenses in the vagina, a site where these defenses are essential to protecting the host upper reproductive tract from invasion by pathogens, is as yet rudimentary. Specifically, little is known about the pattern-recognition component of vaginal innate immunity, the relationship of pattern-recognition molecules to known cytokine levels, and the role of gonadal hormones in their regulation. METHOD OF STUDY: We measured levels of Surfactant Protein-A (SP-A), a prototypic innate pattern-recognition protein, in vaginal fluid (VF) and correlated them with levels of IL-1beta and IL-8, two cytokines known to be present in VF. Assays were carried out on VF collected over three consecutive cycles from ten healthy naturally cycling women who were sampled at three specific time points in the menstrual cycle. The three time points were chosen to enable correlation with distinct hormonal states. RESULTS: Both SP-A and cytokines levels were highest 5-6 days after menses (P < 0.05) and were significantly lower at ovulation and mid-luteal phase. CONCLUSION: Surfactant Protein-A, like other host defense molecules in the reproductive tract, appears to be regulated by gonadal hormones. PMID- 22672630 TI - MBL1 genotypes in wild boar populations from Sweden, Austria, the Czech Republic, and Japan. AB - The single nucleotide polymorphism (SNP) G949T in the mannose-binding lectin ( MBL ) 1 gene has been associated with low MBL-A concentration in serum and detected at different frequencies in various European pig populations. However, the origin of this SNP is not known. Part of the MBL1 gene was sequenced in 12 wild boar/Large White crossbred pigs from the second backcross (BC 2 ) generation in a family material originating from two wild boar x Large White intercrosses. Also, MBL-A serum concentration was measured in the entire BC 2 generation (n = 45). Furthermore, the genotypes of 68 wild boars from Sweden, Austria, the Czech Republic, and Japan were determined in regard to five previously described SNPs in MBL1 . The T allele of G949T was present among the BC 2 animals. MBL-A serum concentration in the BC 2 animals showed a bimodal distribution, with one-third of the animals at levels between 0.7 and 1.6 MUg mL(-1) and the remaining pigs at levels around 13 MUg mL(-1) . There was a co-variation between the presence of the T allele and low MBL-A concentration in serum. The genotyping of the wild boars revealed differences between populations. The T allele of G949T was not detected in the Austrian and Japanese samples and is thus unlikely to be an original feature of wild boars. In contrast, it was present at high frequency (0.35) among the Swedish wild boars, probably representing a founder effect. Five MBL1 haplotypes were resolved. Only two of these were present among the Japanese wild boars compared to four in each of the European populations. This difference may reflect differences in selection pressure and population history. PMID- 22672631 TI - Lack of international consensus in low-risk drinking guidelines. AB - INTRODUCTION AND AIMS: To encourage moderate alcohol consumption, many governments have developed guidelines for alcohol intake, guidelines for alcohol consumption during pregnancy and legislation relating to blood alcohol limits when driving. The aim of this study was to determine the degree of international consensus within such guidelines. DESIGN AND METHODS: Official definitions of standard drinks and consumption guidelines were searched for on government websites, including all 27 European Union Member States and countries from all global geographic regions. RESULTS: There was a remarkable lack of agreement about what constitutes harmful or excessive alcohol consumption on a daily basis, a weekly basis and when driving, with no consensus about the ratios of consumption guidelines for men and women. DISCUSSION AND CONCLUSIONS: International consensus in low-risk drinking guidelines is an important--and achievable--goal. Such agreement would facilitate consistent labelling of packaged products and could help to promote moderate alcohol consumption. However, there are some paradoxes related to alcohol content labelling and people's use of such information: although clearer information could increase people's capacity to monitor and regulate their alcohol consumption, not all drinkers are motivated to drink moderately or sensibly, and drinkers who intend to get drunk may use alcohol content labelling to select more alcoholic products. PMID- 22672632 TI - Clinicopathological and genetic characteristics of extraventricular neurocytomas. AB - Extraventricular neurocytoma (EVN) shares histological features with central neurocytoma, but has a wide morphological spectrum. Little is known regarding its clinicopathologic nature, biological behavior and genetic abnormalities. The aim of this study is to examine the diagnostic criteria, genetic abnormalities and biological behavior of EVN. Clinicopathological and molecular genetic studies were performed in seven EVNs. Among them, three cases showed atypical histology. Immunohistochemically, synaptophysin was robustly positive, but neuronal muclear antigen was positive in only half the cases (4/7cases). Isocitrate dehydrogenase enzyme isoform 1 (IDH1) (H09 immunostaining), alpha-internexin and p53 were negative in all cases. One case was positive for galectin-3. None of the cases showed IDH1 R132 and IDH2 R172 mutation by direct sequencing. One case showed high polysomy of the epidermal growth factor receptor (EGFR) gene; however, O6 methylguanine-DNA methyltransferase (MGMT) promoter methylation and 1p/19q co deletion were not detected. Array-based comparative genomic hybridization (CGH) study was performed in two cases, revealing different profiles, with loss and gain of multiple chromosomal loci. Two children (18%) had tumor recurrence after initial surgery, and one of them showed worse histology at recurrence and EGFR high polysomy. One patient died from the disease at 18.5 months after surgery. From our study, we concluded that EVNs were characterized by the absence of p53 overexpression, alpha-internexin positivity, MGMT promotor methylation and IDH1/IDH2 mutation. Oligodendrocyte transcription factor 2 expression was seen in a scattered positive pattern but quite large numbers of tumor cells were negative. EVN is a WHO grade II tumor but some cases (2/7 cases in our series) can show late recurrence but mortality is low (1/7 cases in our series). CGH study suggested genetic heterogeneity of EVNs and unknown subclassification, which requires verification in more cases. PMID- 22672633 TI - Fractional carbon dioxide laser treatment to enhance skin permeation of ascorbic acid 2-glucoside with minimal skin disruption. AB - BACKGROUND: Topical treatment with vitamin C has been used to treat photoaged skin and as a skin whitener, but no standard procedure exists for percutaneous delivery. OBJECTIVE: To compare skin histology and the permeation of ascorbic acid 2-glucoside (AA2G) after fractional and conventional carbon dioxide (CO(2) ) laser pretreatment. METHODS: The effect on porcine skin of treatment with different strengths of fractional and conventional CO(2) laser treatment was examined using scanning electron microscopy and transmission electron microscopy. Permeation of AA2G through porcine skin was tested in vitro using a Franz diffusion chamber. In vivo changes in fluorescein thiocyanate permeability in nude mice were examined using confocal laser scanning microscopy. RESULTS: Fractional CO(2) laser treatment with four or fewer passes caused less disruption than conventional laser treatment at the same fluence. AA2G permeation using four passes of fractional laser treatment was similar to that seen with conventional CO(2) laser treatment of the same fluence. Changes in permeability and in depth of permeation were higher with conventional than fractional laser treatment. CONCLUSION: Fractional CO(2) laser treatment can cause similar transdermal delivery of AA2G to conventional laser treatment with less skin disruption and a different pattern of histologic change. PMID- 22672634 TI - Evidence of the receptor-mediated influence of melatonin on pancreatic glucagon secretion via the Galphaq protein-coupled and PI3K signaling pathways. AB - Melatonin has been shown to modulate glucose metabolism by influencing insulin secretion. Recent investigations have also indicated a regulatory function of melatonin on the pancreatic alpha-cells. The present in vitro and in vivo studies evaluated whether melatonin mediates its effects via melatonin receptors and which signaling cascade is involved. Incubation experiments using the glucagon producing mouse pancreatic alpha-cell line alphaTC1 clone 9 (alphaTC1.9) as well as isolated pancreatic islets of rats and mice revealed that melatonin increases glucagon secretion. Preincubation of alphaTC1.9 cells with the melatonin receptor antagonists luzindole and 4P-PDOT abolished the glucagon-stimulatory effect of melatonin. In addition, glucagon secretion was lower in the pancreatic islets of melatonin receptor knockout mice than in the islets of the wild-type (WT) control animals. Investigations of melatonin receptor knockout mice revealed decreased plasma glucagon concentrations and elevated mRNA expression levels of the hepatic glucagon receptor when compared to WT mice. Furthermore, studies using pertussis toxin, as well as measurements of cAMP concentrations, ruled out the involvement of Galphai- and Galphas-coupled signaling cascades in mediating the glucagon increase induced by melatonin. In contrast, inhibition of phospholipase C in alphaTC1.9 cells prevented the melatonin-induced effect, indicating the physiological relevance of the Galphaq-coupled pathway. Our data point to the involvement of the phosphatidylinositol 3-kinase signaling cascade in mediating melatonin effects in pancreatic alpha-cells. In conclusion, these findings provide evidence that the glucagon-stimulatory effect of melatonin in pancreatic alpha-cells is melatonin receptor mediated, thus supporting the concept of melatonin-modulated and diurnal glucagon release. PMID- 22672635 TI - Hemolysis induced by an extreme mountain ultra-marathon is not associated with a decrease in total red blood cell volume. AB - Prolonged running is known to induce hemolysis. It has been suggested that hemolysis may lead to a significant loss of red blood cells; however, its actual impact on the erythrocyte pool is unknown. Here, we test the hypothesis that prolonged running with high hemolytic potential decreases total red blood cell volume (RCV). Hemolysis (n = 22) and RCV (n = 19) were quantified in ultra marathon runners before and after a 166-km long mountain ultra-endurance marathon (RUN) with 9500 m of altitude gain/loss. Assessment of total hemoglobin mass (Hbmass) and RCV was performed using a carbon monoxide rebreathing technique. RUN induced a marked acute-phase response and promoted hemolysis, as shown by a decrease in serum haptoglobin (P < 0.05). Elevated serum erythropoietin concentration and reticulocyte count after RUN were indicative of erythropoietic stimulation. Following RUN, runners experienced hemodilution, mediated by a large plasma volume expansion and associated with a large increase in plasma aldosterone. However, neither Hbmass nor RCV were found to be altered after RUN. Our findings indicate that mechanical/physiological stress associated with RUN promotes hemolysis but this has no impact on total erythrocyte volume. We therefore suggest that exercise 'anemia' is entirely due to plasma volume expansion and not to a concomitant decrease in RCV. PMID- 22672636 TI - Traditional food and herbal uses of wild plants in the ancient South-Slavic diaspora of Mundimitar/Montemitro (Southern Italy). AB - BACKGROUND: In Europe, only a limited number of cross-cultural comparative field studies or meta-analyses have been focused on the dynamics through which folk plant knowledge changes over space and time, while a few studies have contributed to the understanding of how plant uses change among newcomers. Nevertheless, ethnic minority groups and/or linguistic "isles" in Southern and Eastern Europe may provide wonderful arenas for understanding the various factors that influence changes in plant uses. METHODS: A field ethnobotanical study was carried out in Mundimitar (Montemitro in Italian), a village of approx. 450 inhabitants, located in the Molise region of South-Eastern Italy. Mundimitar is a South-Slavic community, composed of the descendants of people who migrated to the area during the first half of the 14th century, probably from the lower Neretva valley (Dalmatia and Herzegovina regions). Eighteen key informants (average age: 63.7) were selected using the snowball sampling technique and participated in in-depth interviews regarding their Traditional Knowledge (TK) of the local flora. RESULTS: Although TK on wild plants is eroded in Montemitro among the youngest generations, fifty-seven taxa (including two cultivated species, which were included due to their unusual uses) were quoted by the study participants. Half of the taxa have correspondence in the Croatian and Herzegovinian folk botanical nomenclature, and the other half with South-Italian folk plant names. A remarkable link to the wild vegetable uses recorded in Dalmatia is evident. A comparison of the collected data with the previous ethnobotanical data of the Molise region and of the entire Italian Peninsula pointed out a few uses that have not been recorded in Italy thus far: the culinary use of boiled black bryony (Tamus communis) shoots in sauces and also on pasta; the use of squirting cucumber ( Ecballium elaterium) juice for treating malaria in humans; the aerial parts of the elderberry tree ( Sambucus nigra) for treating erysipelas in pigs; the aerial parts of pellitory ( Parietaria judaica) in decoctions for treating haemorrhoids. CONCLUSIONS: The fact that half of the most salient species documented in our case study - widely available both in Molise and in Dalmatia and Herzegovina - retain a Slavic name could indicate that they may have also been used in Dalmatia and Herzegovina before the migration took place. However, given the occurrence of several South-Italian plant names and uses, also a remarkable acculturation process affected the Slavic community of Montemitro during these last centuries. Future directions of research should try to simultaneously compare current ethnobotanical knowledge of both migrated communities and their counterparts in the areas of origin. PMID- 22672637 TI - Differential expression of proteins associated with seasonal bud dormancy at four critical stages in Japanese apricot. AB - Dormancy is of great significance in the growth and development of deciduous fruit trees. We used a combination of two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionisation time of flight/time of flight mass spectrometry (MALDI-TOF/TOF MS) to identify the differentially expressed proteome of Japanese apricot flower buds at four critical stages, from paradormancy before leaf fall to dormancy release. More than 400 highly reproducible protein spots (P < 0.05) were detected: 34 protein spots showed a greater than twofold difference in expression values, of which 32 protein spots were confidently identified from databases. Identified proteins were classified into six functional categories: stress response and defence (11), energy metabolism (ten), protein metabolism (five), cell structure (three), transcription (one) and unclassified (two). The glyoxalase I homologue could help Japanese apricot survival under various abiotic and biotic stresses, greatly contributing to its dormancy. Enolase, thioredoxin family proteins and triose phosphate isomerase provide adequate energy to complete consecutive dormancy release and bud break in Japanese apricot. Cinnamyl alcohol dehydrogenase 9 and arginase enhance the resilience of plants, enabling them to complete dormancy safely. Analysis of functions of identified proteins and related metabolic pathways will increase our knowledge of dormancy in woody plants. PMID- 22672638 TI - Molecular quantification of Saccharomyces cerevisiae alpha-pheromone secretion. AB - Saccharomyces cerevisiae yeast cells court each other by producing an attractive sex pheromone specific to their mating type. Cells detect the sex pheromone from potential mates using a well-defined intracellular signalling cascade that has become a model for studying signal transduction. In contrast, the factors contributing to the production of pheromone itself are poorly characterized, despite the widespread use of the S. cerevisiae alpha-pheromone secretion pathway in industrial fungal protein expression systems. Progress in understanding pheromone secretion has been hindered by a lack of a precise and quantitative pheromone production assay. Here, we present an ELISA-based method for the quantification of alpha-pheromone secretion. In the absence of pheromone from the opposite mating type, we found that each cell secretes over 550 mature alpha pheromone peptides per second; 90% of this total was produced from MF alpha1. The addition of a-pheromone more than doubled total alpha-pheromone secretion. This technique offers several improvements on current methods for measuring alpha pheromone production and will allow detailed investigation of the factors regulating pheromone production in yeast. PMID- 22672639 TI - The liver in painting: a case of abstraction. PMID- 22672640 TI - Controlled attenuation parameter (CAP): a new device for fast evaluation of liver fat? PMID- 22672641 TI - Anticoagulation in cirrhosis. PMID- 22672642 TI - Non-invasive diagnosis of liver steatosis using controlled attenuation parameter (CAP) and transient elastography. AB - INTRODUCTION: Recently, a study showed that Controlled Attenuation Parameter (CAP), evaluated with transient elastography, could efficiently separate steatosis grades. The aim of this study was to prospectively evaluate the performance of CAP for the diagnosis of steatosis in patients with chronic liver disease. PATIENTS AND METHODS: Consecutive patients with chronic liver disease had steatosis diagnosis using CAP, blood sample and liver biopsy. Steatosis was graded as the percentage of hepatocytes with fat: S0 <= 10%, S1: 11 ~ 33%, S2: 34 ~ 66%, S3 >= 67%. RESULTS: Characteristics of the 112 patients included were as follows: age 54 years, BMI 26 kg m(-) 2, HCV 36%, NAFLD 25%. Steatosis repartition was: S0 52%, S1 19%, S2 14%, S3 15%. CAP was significantly correlated with SteatoTest, Fatty Liver Index (FLI), percentage of steatosis on liver biopsy, steatosis grade and slightly with liver stiffness, but not with fibrosis and activity grade on liver biopsy. Using CAP vs SteatoTest vs FLI score, Area Under the Receiver-Operating Characteristics (ROC) curves (AUROC)s were 0.84 vs 0.72 vs 0.72 for the diagnosis of steatosis >= S1, 0.86 vs 0.73 vs 0.71 for the diagnosis of steatosis >= S2, and 0.93 vs 0.73 vs 0.75 for the diagnosis of steatosis S3 respectively. For a sensitivity >= 90%, cut-offs of CAP were 215 dB m(-1) for S >= 1, 252 dB m(-1) for S >= 2, and 296 dB m(-1) for S3. CONCLUSION: CAP is very efficient to detect even low grade steatosis. CAP being implemented on FibroScan((r)) (Echosens, Paris, France), both steatosis and fibrosis can be evaluated simultaneously, enlarging the spectrum of non-invasive techniques for the management of chronic liver diseases. PMID- 22672643 TI - TNF-alpha neutralization improves experimental hepatopulmonary syndrome in rats. AB - BACKGROUND/AIM: TNF-alpha is increased in hepatopulmonary syndrome (HPS). Pentoxifylline (PTX) mitigated experimental HPS through the inhibition of TNF alpha. However, PTX has pleiotropic effects besides the inhibition of TNF-alpha. This study is to neutralize TNF-alpha with specific monoclonal antibody to TNF alpha (TNF-alpha McAb) to investigate the effect of TNF-alpha on HPS. MATERIALS AND METHODS: Hepatopulmonary syndrome was induced by common bile duct ligation (CBDL); controls were sham operated. The endpoints were 1, 2, 3, 4 and 5 weeks after surgery. (99m) Technetium-macroaggregated albumin (Tc-MAA) was to evaluate intrapulmonary arteriovenous shunts; Portal venous pressure, cardiac output and mean blood pressure (MAP) were also measured. Serum was for Alanine transaminase (ALT), endotoxin, TNF-alpha and nitric oxide (NO) measurements, liver for histology, lung for histology and iNOS, PI3K/Akt expression assay. RESULTS: Portal vein pressure was significantly elevated and MAP decreased in CBDL rats. Tc-MAA was mainly located in lung and very weak in brain in sham group and mainly in brain of CBDL rats. TNF-alpha McAb significantly decreased the radioactivity in the brain, reduced cardiac output, increased MAP and systemic vascular resistance (SVR) in CBDL animals. Serum ALT, endotoxin, TNF-alpha and NO were significantly increased. TNF-alpha McAb significantly decreased these serum indices in CBDL rats. TNF-alpha McAb significantly alleviated liver damage, decreased alveolar-arterial gradient and inhibited iNOS, PI3K/Akt and p-Akt expression in lung tissue. Furthermore, TNF-alpha McAb significantly attenuated the inflammatory response in lung. CONCLUSION: TNF-alpha McAb improves HPS in cirrhotic rats; this effect is likely mediated through the inhibition of TNF alpha PI3K/Akt-NO pathway. PMID- 22672644 TI - Changes in sequences of core region, interferon sensitivity-determining region and interferon and ribavirin resistance-determining region of hepatitis C virus genotype 1 during interferon-alpha and ribavirin therapy, and efficacy of retreatment. AB - AIM: Some regions associated with sensitivity to interferon-alpha and ribavirin have been identified in the hepatitis C virus (HCV) genome, including amino acid 70 in the core region (core a.a. 70), a.a. 2209-2248 (interferon sensitivity determining region, ISDR) and a.a. 2334-2379 (interferon and ribavirin resistance determining region, IRRDR). METHODS: We examined changes in the sequences of these regions in 25 patients with chronic HCV genotype 1 infection who had not had sustained virological response (SVR) to interferon-alpha and ribavirin for 24 48 weeks and subsequently received retreatment for 48-72 weeks. RESULTS: At baseline, the core a.a. 70 was mutant (resistant) type in seven patients. At the start of retreatment, the core a.a. 70 had changed from sensitive to resistant type in 2 patients, and SVR was not achieved by retreatment. The ISDR variations were resistant type (0-1 mutations) in 17 patients at baseline. After 2 weeks of treatment, amino acid change was found in two patients; in one, the substitutions returned to baseline status after treatment, and in the other, the substitution persisted. At the start of retreatment, ISDR sequences had changed from resistant to sensitive type in two patients and SVR was achieved and from sensitive to resistant type in three patients and SVR was not achieved. The IRRDR variations were resistant type (<6 mutations) in 19 patients at baseline and at the start of retreatment. CONCLUSION: Sequences of the core region and ISDR sometimes change during anti-HCV therapy, potentially affecting the outcomes of retreatment. PMID- 22672645 TI - Real-time PCR as an effective technique to assess the impact of phoresy by Paenibacillus sp. bacteria on Steinernema diaprepesi nematodes in nature. AB - Quantitative real-time PCR (qPCR) is a powerful tool to study species of cryptic organisms in complex food webs. This technique was recently developed to detect and quantify several species of entomopathogenic nematodes (EPNs), which are widely used for biological control of insects, and some natural enemies of EPNs such as nematophagous fungi and the phoretic bacteria Paenibacillus sp. and Paenibacillus nematophilus. A drawback to the use of primers and TaqMan probes designed for Paenibacillus sp. is that the qPCR also amplified Paenibacillus thiaminolyticus and Paenibacillus popilliae, two closely related species that are not phoretically associated with EPNs. Here, we report that the detection of Paenibacillus sp. DNA in nematode samples was two orders of magnitude greater (P < 0.001) when the bacterium was added to soil together with its EPN species specific host Steinernema diaprepesi than when it was added concomitantly with other EPNs or with species of bacterial-feeding nematodes. Just 6% of samples detected trace amounts of P. thiaminolyticus and P. popilliae exposed to the same experimental conditions. Thus, although the molecular assay detects Paenibacillus spp. DNA in nonphoretic associations, the levels are essentially background compared to the detection of Paenibacillus sp. in association with its nematode host. PMID- 22672646 TI - Biomine: predicting links between biological entities using network models of heterogeneous databases. AB - BACKGROUND: Biological databases contain large amounts of data concerning the functions and associations of genes and proteins. Integration of data from several such databases into a single repository can aid the discovery of previously unknown connections spanning multiple types of relationships and databases. RESULTS: Biomine is a system that integrates cross-references from several biological databases into a graph model with multiple types of edges, such as protein interactions, gene-disease associations and gene ontology annotations. Edges are weighted based on their type, reliability, and informativeness. We present Biomine and evaluate its performance in link prediction, where the goal is to predict pairs of nodes that will be connected in the future, based on current data. In particular, we formulate protein interaction prediction and disease gene prioritization tasks as instances of link prediction. The predictions are based on a proximity measure computed on the integrated graph. We consider and experiment with several such measures, and perform a parameter optimization procedure where different edge types are weighted to optimize link prediction accuracy. We also propose a novel method for disease-gene prioritization, defined as finding a subset of candidate genes that cluster together in the graph. We experimentally evaluate Biomine by predicting future annotations in the source databases and prioritizing lists of putative disease genes. CONCLUSIONS: The experimental results show that Biomine has strong potential for predicting links when a set of selected candidate links is available. The predictions obtained using the entire Biomine dataset are shown to clearly outperform ones obtained using any single source of data alone, when different types of links are suitably weighted. In the gene prioritization task, an established reference set of disease-associated genes is useful, but the results show that under favorable conditions, Biomine can also perform well when no such information is available.The Biomine system is a proof of concept. Its current version contains 1.1 million entities and 8.1 million relations between them, with focus on human genetics. Some of its functionalities are available in a public query interface at http://biomine.cs.helsinki.fi, allowing searching for and visualizing connections between given biological entities. PMID- 22672647 TI - Co-ordinate regulation of cytokinin gene family members during flag leaf and reproductive development in wheat. AB - BACKGROUND: As the global population continues to expand, increasing yield in bread wheat is of critical importance as 20% of the world's food supply is sourced from this cereal. Several recent studies of the molecular basis of grain yield indicate that the cytokinins are a key factor in determining grain yield. In this study, cytokinin gene family members in bread wheat were isolated from four multigene families which regulate cytokinin synthesis and metabolism, the isopentenyl transferases (IPT), cytokinin oxidases (CKX), zeatin O glucosyltransferases (ZOG), and beta-glucosidases (GLU). As bread wheat is hexaploid, each gene family is also likely to be represented on the A, B and D genomes. By using a novel strategy of qRT-PCR with locus-specific primers shared among the three homoeologues of each family member, detailed expression profiles are provided of family members of these multigene families expressed during leaf, spike and seed development. RESULTS: The expression patterns of individual members of the IPT, CKX, ZOG, and GLU multigene families in wheat are shown to be tissue- and developmentally-specific. For instance, TaIPT2 and TaCKX1 were the most highly expressed family members during early seed development, with relative expression levels of up to 90- and 900-fold higher, respectively, than those in the lowest expressed samples. The expression of two cis-ZOG genes was sharply increased in older leaves, while an extremely high mRNA level of TaGLU1-1 was detected in young leaves. CONCLUSIONS: Key genes with tissue- and developmentally specific expression have been identified which would be prime targets for genetic manipulation towards yield improvement in bread wheat breeding programmes, utilising TILLING and MAS strategies. PMID- 22672648 TI - Apolipoprotein B/apolipoprotein A1 ratio is a good predictive marker of metabolic syndrome and pre-metabolic syndrome in Chinese adolescent women with polycystic ovary syndrome. AB - AIM: The apolipoprotein B/apolipoprotein A1 (ApoB/ApoA1) ratio is well known to be related to metabolic syndrome (MS) and its components in adults of different races. There is low prevalence of MS but high occurrence of various metabolic disorders in Chinese adolescent women with polycystic ovary syndrome (PCOS). We sought to assess if the ApoB/ApoA1 ratio can be used as a predictive marker of MS and pre-MS in Chinese adolescent women with PCOS. MATERIAL AND METHODS: This cross-sectional study included 160 Chinese adolescent women. Based on International Diabetes Federation criteria for MS, patients who had no less than two components of MS but did not meet the criteria for the diagnosis of MS were considered as having pre-MS. RESULTS: The ApoB/ApoA1 ratio was higher in obese subjects with high free androgen index (FAI). The ApoB/ApoA1 ratio increased significantly as the number of MS components increased and provided 87.5% of sensitivity and 78.9% of specificity with a threshold value of 0.63 for MS, 86.2% of sensitivity and 79.4% of specificity with a threshold value of 0.58 for pre-MS in Chinese adolescent women with PCOS. CONCLUSION: The ApoB/ApoA1 ratio was a good predictive marker of MS and pre-MS in Chinese adolescent women with PCOS. FAI could be involved in obesity-related metabolic abnormalities. PMID- 22672649 TI - Top 10 plant pathogenic bacteria in molecular plant pathology. AB - Many plant bacteriologists, if not all, feel that their particular microbe should appear in any list of the most important bacterial plant pathogens. However, to our knowledge, no such list exists. The aim of this review was to survey all bacterial pathologists with an association with the journal Molecular Plant Pathology and ask them to nominate the bacterial pathogens they would place in a 'Top 10' based on scientific/economic importance. The survey generated 458 votes from the international community, and allowed the construction of a Top 10 bacterial plant pathogen list. The list includes, in rank order: (1) Pseudomonas syringae pathovars; (2) Ralstonia solanacearum; (3) Agrobacterium tumefaciens; (4) Xanthomonas oryzae pv. oryzae; (5) Xanthomonas campestris pathovars; (6) Xanthomonas axonopodis pathovars; (7) Erwinia amylovora; (8) Xylella fastidiosa; (9) Dickeya (dadantii and solani); (10) Pectobacterium carotovorum (and Pectobacterium atrosepticum). Bacteria garnering honourable mentions for just missing out on the Top 10 include Clavibacter michiganensis (michiganensis and sepedonicus), Pseudomonas savastanoi and Candidatus Liberibacter asiaticus. This review article presents a short section on each bacterium in the Top 10 list and its importance, with the intention of initiating discussion and debate amongst the plant bacteriology community, as well as laying down a benchmark. It will be interesting to see, in future years, how perceptions change and which bacterial pathogens enter and leave the Top 10. PMID- 22672650 TI - Abutment design for implant-supported indirect composite molar crowns: reliability and fractography. AB - PURPOSE: To investigate the reliability of titanium abutments veneered with indirect composites for implant-supported crowns and the possibility to trace back the fracture origin by qualitative fractographic analysis. MATERIALS AND METHODS: Large base (LB) (6.4-mm diameter base, with a 4-mm high cone in the center for composite retention), small base (SB-4) (5.2-mm base, 4-mm high cone), and small base with cone shortened to 2 mm (SB-2) Ti abutments were used. Each abutment received incremental layers of indirect resin composite until completing the anatomy of a maxillary molar crown. Step-stress accelerated-life fatigue testing (n = 18 each) was performed in water. Weibull curves with use stress of 200 N for 50,000 and 100,000 cycles were calculated. Probability Weibull plots examined the differences between groups. Specimens were inspected in light polarized and scanning electron microscopes for fractographic analysis. RESULTS: Use level probability Weibull plots showed Beta values of 0.27 for LB, 0.32 for SB-4, and 0.26 for SB-2, indicating that failures were not influenced by fatigue and damage accumulation. The data replotted as Weibull distribution showed no significant difference in the characteristic strengths between LB (794 N) and SB 4 abutments (836 N), which were both significantly higher than SB-2 (601 N). Failure mode was cohesive within the composite for all groups. Fractographic markings showed that failures initiated at the indentation area and propagated toward the margins of cohesively failed composite. CONCLUSIONS: Reliability was not influenced by abutment design. Qualitative fractographic analysis of the failed indirect composite was feasible. PMID- 22672651 TI - Comprehensive geriatric functional analysis of elderly populations in four categories of the long-term care insurance system in a rural, depopulated and aging town in Japan. AB - AIM: The aim of this study was to show which dimensions of functions differ among community-dwelling elderly participants in four different certification levels of the current long-term care insurance system (LTCI) in a rural, depopulated and aging town in Japan, with special consideration for strengths and weaknesses of the LTCI. METHODS: The study population consisted of 1077 community-dwelling elderly participants aged 65 years and older, with LTCI certification comprising 542 uncertified elderly (Ippan-Koureisya), 437 specified elderly (Tokutei Koreisha), 57 support-level elderly (Youshien-Koureisha) and 41 care-level elderly (Youkaigo-Ninteisha). Each participant was rated regarding their health status, with question topics including basic activities of daily living (ADL), the Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC), the 15-item Geriatric Depression Scale (GDS-15), 21-item Fall Risk Index (FRI 21), the quantitative subjective quality of life (QOL), current medical situation, past medical histories and social backgrounds. RESULTS: The scores in basic ADL, each item of the TMIG-IC and five items of the quantitative subjective QOL were significantly lower, and the scores in GDS-15 and in FRI-21 were significantly higher according to certification level, in order of uncertified, specified, support-level and care-level elderly in a dose-response manner. Exercise and drinking habits were significantly less common in support- or care level elderly than in specified or uncertified elderly. The prevalence of taking antihypertensive, antihyperlipidemia, antidepressant or sleeping medications was significantly higher in the support- or care-level elderly than in uncertified or specified elderly people. Support- or care-level elderly also had a significantly higher prevalence of past medical histories of stroke, bone fractures, osteoarthropathy, heart disease and cancer than uncertified or specified elderly people. CONCLUSION: Actual standardized quantitative and qualitative geriatric functions of the elderly among four categories in newly revised LTCI system were shown in a depopulated and aging town in Japan. Based on the actual situation of functions of the elderly, the strengths and weaknesses of the current LTCI system were reconsidered. Further research on the measures to prevent future dependency among the specified and support-level elderly is required. PMID- 22672652 TI - Time course pathogenesis of sulphur mustard-induced skin lesions in mouse model. AB - Sulphur mustard (SM) is a bifunctional alkylating agent that causes cutaneous blistering in humans and animals. In this study, we have presented closer views on pathogenesis of SM-induced skin injury in a mouse model. SM diluted in acetone was applied once dermally at a dose of 5 or 10 mg/kg to Swiss albino mice. Skin was dissected out at 0, 1, 3, 6, 12, 24, 48, 72 and 168 hours, post-SM exposure for studying histopathological changes and immunohistochemistry of inflammatory reparative biomarkers, namely, transforming growth factor alpha (TGF-alpha), fibroblast growth factor (FGF), endothelial nitric oxide synthase (eNOS) and interlukin 6 (IL-6). Histopathological changes were similar to other mammalian species and basal cell damage resembled the histopathological signs observed with vesication in human skin. Inflammatory cell recruitment at the site of injury was supported by differential expressions of IL-6 at various stages. Time-dependent expressions of eNOS played pivotal roles in all the events of wound healing of SM induced skin lesions. TGF-alpha and FGF were strongly associated with keratinocyte migration, re-epithelialisation, angiogenesis, fibroblast proliferation and cell differentiation. Furthermore, quantification of the tissue leukocytosis and DNA damage along with semiquantitative estimation of re epithelialisation, fibroplasia and neovascularisation on histomorphologic scale could be efficiently used for screening the efficacy of orphan drugs against SM induced skin injury. PMID- 22672653 TI - Combined modality treatment for complex fistulating perianal Crohn's disease. AB - AIM: Perianal disease affects 33% (range 8-90%) of patients with Crohn's disease. Fistulae are often complex and their management is often difficult and unsatisfactory. This study was a retrospective assessment of a combination of surgical treatment with a standardized protocol of infliximab (IFX) therapy. METHOD: A consecutive series of patients with complex perianal Crohn's disease, presenting between January 2003 and June 2008, were included. Acute sepsis was initially treated with antibiotics and/or surgical drainage (MRI guided when appropriate) and loose seton insertion. IFX was given at 5 mg/kg, at 0, 2 and 6 weeks. End-points were complete, partial or no response. Setons were empirically removed after the second cycle of IFX. RESULTS: Forty-eight patients, average age 46 (range 24-82)years, with perianal Crohn's disease were identified. Three patients stopped IFX after the second infusion, either because of allergy (two patients) or for failure to respond (one patient). Fourteen patients were given maintenance IFX at 8-weekly intervals. Results were recorded for 48 patients, of whom 14 (29%) had a complete response, 20 (42%) had a partial response and 14 (29%) had no response to treatment. Outpatient follow-up was for a median of 20 months. CONCLUSION: Combining surgical procedures with IFX resulted in complete and partial remission in 29% and 42% of patients, respectively. No serious side effects occurred. Using a combined, intensive medico-surgical approach, good initial control of perianal disease was achieved safely. PMID- 22672654 TI - School day segmented physical activity patterns of high and low active children. AB - BACKGROUND: Variability exists in children's activity patterns due to the association with environmental, social, demographic, and inter-individual factors. This study described accelerometer assessed physical activity patterns of high and low active children during segmented school week days whilst controlling for potential correlates. METHODS: Two hundred and twenty-three children (mean age: 10.7 +/- 0.3 yrs, 55.6% girls, 18.9% overweight/obese) from 8 north-west England primary schools wore ActiGraph GT1M accelerometers for 7 consecutive days during autumn of 2009. ActiGraph counts were converted to minutes of moderate (MPA), vigorous (VPA) and moderate-to-vigorous (MVPA) physical activity. Children were classified as high active (HIGH) or low active (LOW) depending on the percentage of week days they accumulated at least 60 minutes of MVPA. Minutes spent in MPA and VPA were calculated for school time and non-school time and for five discrete school day segments (before-school, class time, recess, lunchtime, and after-school). Data were analysed using multi-level modelling. RESULTS: The HIGH group spent significantly longer in MPA and/or VPA before-school, during class time, lunchtime, and after-school (P < .05), independent of child and school level factors. The greatest differences occurred after-school (MPA = 5.5 minutes, VPA = 3.8 minutes, P < 0.001). MPA and VPA were also associated with gender, BMI z-score, number of enrolled children, playground area per student, and temperature, depending on the segment analysed.The additive effect of the segment differences was that the HIGH group accumulated 12.5 minutes per day more MVPA than the LOW group. CONCLUSIONS: HIGH active children achieved significantly more MPA and VPA than LOW active during four of the five segments of the school day when analyses were adjusted for potential correlates. Physical activity promotion strategies targeting low active children during discretionary physical activity segments of the day, and particularly via structured afterschool physical activity programs may be beneficial. PMID- 22672655 TI - Comparing alcohol affordability in 65 cities worldwide. AB - INTRODUCTION AND AIMS: To develop a measure of alcohol affordability (AA) and compare the AA of 65 cities worldwide. DESIGN AND METHODS: In this paper, AA is defined as the proportion of median daily income needed to buy a certain quantity of certain alcoholic beverages. The income data and the price of alcoholic beverages were drawn from the Union Bank of Switzerland survey and the Economist Intelligence Unit respectively. RESULTS: A large majority of cities (87.7%, n = 57) had a high level of AA. The top 20 ranking was occupied by European and American cities with Tokyo in the Western Pacific region being the exception. All cities belonging to high-income countries had high levels of AA. However, two cities with low-level AA came from low-middle-income countries instead of low income countries. DISCUSSION AND CONCLUSIONS: The findings have shown that alcohol consumption is highly affordable in many cities. If price policy is being considered as policy instrument of alcohol control, it is in urgent need of price adjustments. More specifically, the new emerging economies play a significant role in the world alcohol control movement because of their bright economic performance with huge population size. Further studies on AA, especially periodical monitoring and its impacts on alcohol consumption and alcohol related health problems, should be conducted so as to facilitate the formulation and evaluation price measure of alcohol control. PMID- 22672656 TI - Editorial comment to cytoreductive nephrectomy for pT3b-T4 M1 renal cell carcinoma in 39 patients: single center analysis. PMID- 22672657 TI - Detection of the rare HLA-B*40:97 allele in an unrelated Taiwanese bone marrow donor. AB - We detected a rare HLA-B locus allele, B*40:97, in a Taiwanese unrelated donor in our routine HLA SBT (sequence-based typing) exercise for a possible hematopoietic stem cell donation. In exons 2, 3 and 4, the sequence of B*40:97 is identical to the sequence of B*40:02:01 except one nucleotide at nucleotide position 760 (C >T) in exon 4. The nucleotide variation caused one amino acid alteration at residue 230 (L->F). B*40:97 was probably derived from a nucleotide substitution event where C was replaced by T at nucleotide 760 involving B*40:02:01. The HLA A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 haplotype in association with B*40:97 may be deduced as A*26:01-B*40:97-C*03:03-DRB1*11:01-DQB1*03:03. Our recognition of B*40:97 in Taiwanese helps to fill the void of ethnic information for the allele B*40:97 reported to the IMGT/HLA Database. PMID- 22672658 TI - Study of the uterine local immune response in a murine model of embryonic death due to Tritrichomonas foetus. AB - PROBLEM: Bovine tritrichomonosis is a sexually transmitted disease caused by Tritrichomonas foetus, characterized by conceptus loss. We developed a mouse model of tritrichomonosis to study the mechanisms involved in the embryonic death. We hypothesized that embryonic death may be due to an exacerbated maternal response to the pathogen that then affects embryo development. METHOD OF STUDY: We infected BALB/c mice with Tritrichomonas foetus and paired them after confirming active infection. We studied the expression of pro- and anti inflammatory cytokines, markers for T regulatory and T helper 17 cells as well as haem-oxygenase-1 expression in uterine tissue by real-time RT-PCR. RESULTS: As expected, TNF-alpha was augmented in infected animals. IL-10 and IL-4 were also up-regulated. Treg-associated genes were higher expressed in uteri of infected group. In mice that have lost their conceptus after the infection, haem-oxygenase 1 (HO-1) mRNA levels were strongly decreased, while RORgammat mRNA, a reliable marker for Th17, was augmented in uterus. CONCLUSION: A T effector response of type 1 and 17 may be involved in tritrichomonosis-related embryonic death. This alters protective mechanisms as HO-1. Increased regulatory T cells may facilitate embryonic death by promoting the persistence of infection. PMID- 22672659 TI - Genetic deletion of MT(1) and MT(2) melatonin receptors differentially abrogates the development and expression of methamphetamine-induced locomotor sensitization during the day and the night in C3H/HeN mice. AB - This study explored the role of the melatonin receptors in methamphetamine (METH) induced locomotor sensitization during the light and dark phases in C3H/HeN mice with genetic deletion of the MT(1) and/or MT(2) melatonin receptors. Six daily treatments with METH (1.2 mg/kg, i.p.) in a novel environment during the light phase led to the development of locomotor sensitization in wild-type (WT), MT(1)KO and MT(2)KO mice. Following four full days of abstinence, METH challenge (1.2 mg/kg, i.p.) triggered the expression of locomotor sensitization in METH pretreated but not in vehicle (VEH)-pretreated mice. In MT(1)/MT(2)KO mice, the development of sensitization during the light phase was significantly reduced and the expression of sensitization was completely abrogated upon METH challenge. During the dark phase the development of locomotor sensitization in METH pretreated WT, MT(1)KO and MT(2)KO mice was statistically different from VEH treated controls. However, WT and MT(2)KO, but not MT(1)KO mice receiving repeated VEH pretreatments during the dark phase expressed a sensitized response to METH challenge that is of an identical magnitude to that observed upon 6 days of METH pretreatment. We conclude that exposure to a novel environment during the dark phase, but not during the light phase, facilitated the expression of sensitization to a METH challenge in a manner dependent on MT(1) melatonin receptor activation by endogenous melatonin. We suggest that MT(1) and MT(2) melatonin receptors are potential targets for pharmacotherapeutic intervention in METH abusers. PMID- 22672660 TI - Primary traumatic patellar dislocation. AB - Acute traumatic patellar dislocation is a common injury in the active and young adult populations. MRI of the knee is recommended in all patients who present with acute patellar dislocation. Numerous operative and non-operative methods have been described to treat the injuries; however, the ideal management of the acute traumatic patellar dislocation in young adults is still in debate. This article is intended to review the studies to the subjects of epidemiology, initial examination and management. PMID- 22672664 TI - Prognostic categories and timing of negative prognostic communication from critical care physicians to family members at end-of-life in an intensive care unit. AB - Negative prognostic communication is often delayed in intensive care units, which limits time for families to prepare for end-of-life. This descriptive study, informed by ethnographic methods, was focused on exploring critical care physician communication of negative prognoses to families and identifying timing influences. Prognostic communication of critical care physicians to nurses and family members was observed and physicians and family members were interviewed. Physician perception of prognostic certainty, based on an accumulation of empirical data, and the perceived need for decision-making, drove the timing of prognostic communication, rather than family needs. Although prognoses were initially identified using intuitive knowledge for patients in one of the six identified prognostic categories, utilizing decision-making to drive prognostic communication resulted in delayed prognostic communication to families until end of-life (EOL) decisions could be justified with empirical data. Providers will better meet the needs of families who desire earlier prognostic information by separating prognostic communication from decision-making and communicating the possibility of a poor prognosis based on intuitive knowledge, while acknowledging the uncertainty inherent in prognostication. This sets the stage for later prognostic discussions focused on EOL decisions, including limiting or withdrawing treatment, which can be timed when empirical data substantiate intuitive prognoses. This allows additional time for families to anticipate and prepare for end-of-life decision-making. PMID- 22672666 TI - Nodule development on the tropical legume Sesbania virgata under flooded and non flooded conditions. AB - The interaction between the Brazilian pioneer legume Sesbania virgata and its microsymbiont Azorhizobium doebereinerae leads to the formation of nitrogen fixing nodules on roots that grow either in well-aerated soils or in wetlands. We studied the initiation and development of nodules under these alternative conditions. To this end, light and fluorescence microscopy were used to follow the bacterial colonisation and invasion into the host and, by means of transmission electron microscopy, we could observe the intracellular entry. Under hydroponic conditions, intercellular invasion took place at lateral root bases and mature nodules were round and determinate. However, on roots grown in vermiculite that allows aerated growth, bacteria also entered via root hair invasion and nodules were both of the determinate and indeterminate type. Such versatility in entry and developmental plasticity, as previously described in Sesbania rostrata, enables efficient nodulation in both dry and wet environments and are an important adaptive feature of this group of semi-tropical plants that grow in temporarily flooded habitats. PMID- 22672665 TI - Spectrum of toxic hepatitis following intentional paraquat ingestion: analysis of 187 cases. AB - INTRODUCTION: This retrospective observational study examined the clinical features, the degrees of toxic hepatitis, physiological markers and clinical outcomes after intentional paraquat poisoning and sought to determine what association, if any, might exist between these findings. METHODS: A total of 187 patients were referred for management of intentional paraquat ingestion between 2000 and 2010. Patients were categorized into two groups according to their hepatic complication, i.e. with (N = 87) or without (N = 100) toxic hepatitis. Demographic, clinical and laboratory data were obtained for analysis. Mortality rates were also analysed. RESULTS: It was found that patients with toxic hepatitis were younger (39.7 +/- 13.7 vs 44.2 +/- 16.6 year old, P = 0.046), and suffered from greater incidences of acute respiratory failure (63.2 vs 48.0%, P = 0.037) and acute renal failure (75.9 vs 56.0%, P = 0.004) than patients without hepatitis. The hospitalization period was longer in patients with hepatitis than without hepatitis (16.2 +/- 14.6 vs 11.2 +/- 12.1 days, P = 0.012), even though there was no difference in mortality rate between both groups (56.3 vs 53.0%, P = 0.649). Notably, the symptoms of toxic hepatitis developed within 6.7 +/- 6.3 days of exposure to paraquat with aspartate aminotransferase (AST) 138 +/- 156 U/L, alanine aminotransferase (ALT) 127 +/- 114 U/L and total bilirubin 2.7 +/- 2.6 mg/dL. The hepatitis peaked at 9.5 +/- 8.8 days with AST 125 +/- 139 U/L, ALT 183 +/- 181 U/L and total bilirubin 3.2 +/- 3.6 mg/dL. Nevertheless, the symptoms resolved within 17.3 +/- 9.8 days of paraquat exposure, and none of the patients died of hepatic complication. CONCLUSIONS: A substantial proportion of paraquat patients suffered from hepatic complication (46.52%), but the spectrum of hepatitis in these patients seemed mild and transient. PMID- 22672667 TI - On the hypothesis-free testing of metabolite ratios in genome-wide and metabolome wide association studies. AB - BACKGROUND: Genome-wide association studies (GWAS) with metabolic traits and metabolome-wide association studies (MWAS) with traits of biomedical relevance are powerful tools to identify the contribution of genetic, environmental and lifestyle factors to the etiology of complex diseases. Hypothesis-free testing of ratios between all possible metabolite pairs in GWAS and MWAS has proven to be an innovative approach in the discovery of new biologically meaningful associations. The p-gain statistic was introduced as an ad-hoc measure to determine whether a ratio between two metabolite concentrations carries more information than the two corresponding metabolite concentrations alone. So far, only a rule of thumb was applied to determine the significance of the p-gain. RESULTS: Here we explore the statistical properties of the p-gain through simulation of its density and by sampling of experimental data. We derive critical values of the p-gain for different levels of correlation between metabolite pairs and show that B/(2*alpha) is a conservative critical value for the p-gain, where alpha is the level of significance and B the number of tested metabolite pairs. CONCLUSIONS: We show that the p-gain is a well defined measure that can be used to identify statistically significant metabolite ratios in association studies and provide a conservative significance cut-off for the p-gain for use in future association studies with metabolic traits. PMID- 22672668 TI - Serum calcium level is related to both intima-media thickness and carotid atherosclerosis: a neglect risk factor in obese/overweight subjects. AB - BACKGROUND: Experimental studies suggested that high serum calcium may be important in the pathogenesis of vascular diseases. Since calcium seems to affect specifically the cerebrovascular district, aim of this study was to determine the relation between serum calcium levels, within normal range, and subclinical atherosclerosis in the carotid arteries, in a population of obese/overweight subjects. METHODS: In our retrospective study we included 472 subjects (59% female) with body mass index equal to or more than 25 kg/m2. They underwent a physical examination, a biochemical assessment (including calcium evaluation) and a B-mode ultrasonography of the extracranial carotid arteries to detect carotid atherosclerosis presence and to measure intima-media thickness. RESULTS: Mean age of the population was 50 +/-12 years. Prevalence of the Carotid atherosclerosis was 40%. Mean carotid intima-media thickness was 0,66 +/- 0,18 mm. The univariate and multivariate analysis showed an association between calcium and carotid intima-media thickness (p = 0,035). We divided the population in serum calcium tertiles. We found an higher carotid atherosclerosis prevalence in the III tertile in comparison to that of the I tertile (p = 0,039). CONCLUSIONS: In this study we found a positive relation between serum calcium levels, within normal range, and subclinical atherosclerosis in the carotid arteries, in a population of obese/overweight subjects. It is important to consider the impact of the serum calcium levels in the overall risk assessment of patients, at least in obese subjects. PMID- 22672669 TI - Validation of the TonoVet(r) rebound tonometer in normal and glaucomatous cats. AB - Objective To validate intraocular pressure (IOP) readings obtained in cats with the TonoVet((r)) tonometer. Animals studied IOP readings obtained with the TonoVet((r)) were compared to IOP readings determined by manometry and by the Tono-Pen XL(TM) in 1 normal cat and two glaucomatous cats. TonoVet((r)) and Tono Pen XL(TM) readings were also compared in a further six normal and nine glaucomatous cats. Procedures The anterior chambers of both eyes of three anesthetized cats were cannulated and IOP was varied manometrically, first increasing from 5 to 70 mmHg in 5 mmHg increments, then decreasing from 70 to 10 mmHg in 10 mmHg decrements. At each point, two observers obtained three readings each from both eyes, with both the TonoVet((r)) and Tono-Pen XL(TM) . IOP was measured weekly for 8 weeks with both tonometers in six normal and nine glaucomatous unsedated cats. Data were analyzed by linear regression. Comparisons between tonometers and observers were made by paired student t-test. Results The TonoVet((r)) was significantly more accurate than the Tono-Pen XL(TM) (P = 0.001), correlating much more strongly with manometric IOP. In the clinical setting, the Tono-Pen XL(TM) underestimated IOP when compared with the TonoVet((r)) . Conclusions Both the TonoVet((r)) and Tono-Pen XL(TM) provide reproducible IOP measurements in cats; however, the TonoVet((r)) provides readings much closer to the true IOP than the Tono-Pen XL(TM) . The TonoVet((r)) is superior in accuracy to the Tono-Pen XL(TM) for the detection of ocular hypertension and/or glaucoma in cats in a clinical setting. PMID- 22672670 TI - MGMT, GATA6, CD81, DR4, and CASP8 gene promoter methylation in glioblastoma. AB - BACKGROUND: Methylation of promoter region is the major mechanism affecting gene expression in tumors. Recent methylome studies of brain tumors revealed a list of new epigenetically modified genes. Our aim was to study promoter methylation of newly identified epigenetically silenced genes together with already known epigenetic markers and evaluate its separate and concomitant role in glioblastoma genesis and patient outcome. METHODS: The methylation status of MGMT, CD81, GATA6, DR4, and CASP8 in 76 patients with primary glioblastomas was investigated. Methylation-specific PCR reaction was performed using bisulfite treated DNA. Evaluating glioblastoma patient survival time after operation, patient data and gene methylation effect on survival was estimated using survival analysis. RESULTS: The overwhelming majority (97.3%) of tumors were methylated in at least one of five genes tested. In glioblastoma specimens gene methylation was observed as follows: MGMT in 51.3%, GATA6 in 68.4%, CD81 in 46.1%, DR4 in 41.3% and CASP8 in 56.8% of tumors. Methylation of MGMT was associated with younger patient age (p < 0.05), while CASP8 with older (p < 0.01). MGMT methylation was significantly more frequent event in patient group who survived longer than 36 months after operation (p < 0.05), while methylation of CASP8 was more frequent in patients who survived shorter than 36 months (p < 0.05). Cox regression analysis showed patient age, treatment, MGMT, GATA6 and CASP8 as independent predictors for glioblastoma patient outcome (p < 0.05). MGMT and GATA6 were independent predictors for patient survival in younger patients' group, while there were no significant associations observed in older patients' group when adjusted for therapy. CONCLUSIONS: High methylation frequency of tested genes shows heterogeneity of glioblastoma epigenome and the importance of MGMT, GATA6 and CASP8 genes methylation in glioblastoma patient outcome. PMID- 22672671 TI - Risk factors of cesarean delivery at prenatal care, admission and during labor in low-risk pregnancy: multivariate logistic regression analysis. AB - AIM: Risk assessment for cesarean delivery is not a one-time assessment, but rather a procedure that continues throughout pregnancy and labor. The objective of this study was to develop models to determine risk factors of cesarean delivery in three stages in low-risk pregnancy. MATERIAL AND METHODS: The period from pregnancy to childbirth was divided into three stages, including prenatal care, admission and labor. Multivariable logistic regression analysis was used to develop three risk assessment models according to these stages, which were compared by areas under receiver operating characteristic (ROC) curves. RESULTS: We developed three predictive models with different risk factors. The ability of each model to determine the risk of cesarean delivery differed according to the three stages. The ROC curve values differed significantly between the labor (model III) and prenatal care (model I) or admission (model II) models (z=11.43, P<0.001; z=8.18, P<0.001, respectively). There was also a difference in the ROC between models I and II (z=6.76, P<0.001). CONCLUSION: This study shows that the models constructed for the more advanced stages of pregnancy were the more accurate risk factors of cesarean delivery. Therefore, the risk assessment model for cesarean delivery should be differently adapted according to each stage. PMID- 22672672 TI - Structure-oriented review of 14-3-3 protein isoforms in geriatric neuroscience. AB - This review focuses on the possible relevance of 14-3-3 proteins in geriatric neuroscience. 14-3-3 proteins are mainly localized in the synapses and neuronal cytoplasm. These proteins regulate intracellular signal cascades for differentiation, development, growth, apoptosis and survival. Seven isoforms have so far been identified in mammals. The binding motifs and potential functions of 14-3-3 proteins are now recognized to have a wide range of functional relevance. First, we provide a brief summary of the molecular structure and multiple functions of 14-3-3 proteins. Second, we review the involvement of 14-3-3 proteins in common diseases of geriatric neurology, such as Alzheimer's disease and tauopathies, Parkinson's disease and alpha-synucleinopathies, Huntington's disease and polyglutamine diseases, Creutzfeldt-Jakob disease and prion diseases, cerebral infarction, and atherosclerosis. Finally, we discuss the immunohistochemical localization of 14-3-3 proteins and its isoforms during the postnatal development of rat brains as a basis for understanding adult neurogenesis. The elucidation of the isoform-dependent functions of 14-3-3 proteins with regard to brain development might be promising for the future development of novel therapeutic interventions for common diseases of geriatric neurology. PMID- 22672673 TI - Kinematic, strength, and stiffness adaptations after a short-term sled towing training in athletes. AB - One of the most frequently used methods for training the sprint-specific strength is the sled towing. To date, no studies have been conducted to explore the effects of this method after a training period in well-trained athletes. The purpose of this study was to determine the effects of 4 weeks of resisted sprint training with sled towing. Twenty-two trained athletes experienced in the use of weighted sled (WS) participated in the study. They conducted the same 3-week training to level their initial condition. After that they were distributed in two groups, unresisted (UR) and WS training. They carried out the same 4-week, 2 days/week sprint-specific training, only differing in that the experimental group performed sprints with a (WS) which caused a reduction of 7.5% of their maximum velocity. Pre- and posttest were conducted which included the measurement of sprint kinematics, muscular strength (including isoinertial, isokinetic, and jump measurements), and sprinting stiffness (leg and vertical). Results show different adaptations in the groups although no interaction effect was found. The WS group improved the velocity in the transition phase, while the UR group improved the velocity in the maximum velocity phase. No improvements in the height of the jump tests were found. PMID- 22672674 TI - Hem-o-lok clip causing small bowel obstruction after robot-assisted radical prostatectomy. PMID- 22672675 TI - A shortage of caring in British nursing? PMID- 22672676 TI - Saying something interesting about responsibility for health. AB - The concept of responsibility for health is a significant feature of health discourse and public health policy, but application of the concept is poorly understood. This paper offers an analysis of the concept in two ways. Following an examination of the use of the word 'responsibility' in the nursing and wider health literature using three examples, the concept of 'responsibility for health' as fulfilling a social function is discussed with reference to policy documents from the UK. The philosophical literature on moral responsibility is introduced, and in considering two versions, reactive attitudes and accountability, it is argued that in application both can be regarded, though with different emphasis, as being constituted in three parts: (i) a responsible agent; (ii) having obligations (responsibilities); and (iii) being susceptible to being held responsible (that is blamed) if he fails to meet them. The three-stage model is consistent with the examples of the word responsibility in use, but application to the social function model causes a number of problems for healthcare practice, especially for the reactive attitudes account. Apart from considerable problems in stating what exactly the obligations are and how they can be justified; and how blame might justly be apportioned and by whom, the very ideas of obligation and blame are in conflict within healthcare systems and professional nursing practice which have foundations deeply embedded in the notion of the supremacy of personal autonomy. It is concluded that current application of the concept of responsibility for health is conceptually incoherent, and if it is to retain its place in health policy and discourse, urgent remedy is required. PMID- 22672677 TI - The holism of aesthetic knowing in nursing. AB - In 1978, Carper identified 'four fundamental patterns of knowing' that became largely foundational to subsequent epistemological discourse within the nursing discipline. These patterns of empirical, personal, aesthetic, and ethical knowing were presented as conceptually distinct yet related patterns of knowing. In order to provide an alternative conceptualization of aesthetics in nursing, the main tenants of Carper's discussion of aesthetic knowing will be revisited, and the foundations for her arguments will be examined. Specifically, Dewey's Art as Experience will be examined in relation to the 'holism' of nursing, and an alternative position on pragmatic aesthetics in nursing will be offered. A preliminary reintegration of the four patterns of knowing will then be presented as will an example of a potential cultivation of aesthetics in nursing, through an example of Rodin's 19th century sculpture, the Burghers of Calais. PMID- 22672678 TI - Reflexivity and habitus: opportunities and constraints on transformative learning. AB - This paper will explore the relationship between Mezirow's concept of reflexivity and Bourdieu's theory of habitus in order to develop a more robust framework within which critical reflection can take place. Nurse educators have sought to close the theory practice gap through the use of critical reflection. However, we are not convinced that this has produced the depth and quality of reflection required. Furthermore, the contexts in which critical reflection takes place is often sidelined or erased so that the whole impetus in the literature is to educate nurses in reflection rather than empower nurses to understand the complex circumstances and barriers that obstruct critical reflection. This paper argues that the reason for this position is that nurse education does not always acknowledge the role that personal and cultural values systems have on reflective practices. The literature search was undertaken using CINHAL and MEDLINE. Keywords included: values systems, habitus, and critical reflection. Inclusion criteria were determined by the theoretical approach and included seminal texts, from as far back as 1956, to identify key themes. Although critical reflection is a potentially powerful way of enhancing care it has often failed to do so. It is suggested that this is because nurse educators have frequently used models of reflection without considering the impact that student's personal values systems has on their perceptions of care and subsequently care delivery. The purpose of this paper is to promote deeper levels of reflection and is part of a programme of research aimed at developing a more robust approach to reflection in educational practice. PMID- 22672679 TI - The lost path to emancipatory practice: towards a history of reflective practice in nursing. AB - This paper historicizes the taken-for-granted acceptance of reflection as a fundamental professional practice in nursing. It draws attention to the broad application of reflective practice, from pedagogy to practice to regulation, and explores the epistemological basis upon which the authority of reflective discourse rests. Previous work has provided a series of critiques of the logic and suitability of reflective practice across all domains of nursing. The goal of this paper is to commence a history of nursing's reflective identity. The paper begins with a discussion of Dewey and Schon then focuses on Habermas's Theory of Communicative Action as the epistemological basis of reflective practice's standing as a authoritative discourse in nursing. PMID- 22672680 TI - Is there unity within the discipline? AB - This paper will examine a claim that nursing is united by its moral stance. The claim is that there are moral constraints on nurses' actions as people practising nursing (nurses qua nurses) and that they are in some way different from both what for now can be called standard morality and also different from the person's own moral views who also happens to be a nurse, hence the defining and unifying factor for nursing. I will begin by situating the claim within the broader area about the need for a definition to state features that are essential to all and only members of its class. This will highlight the fact that there are two distinct types of definition used by authors seeking to find a unity for nursing. One type of definition has to do with goals or purposes given to nursing and the other with ends discovered as nursing. But even if there are ends waiting to be discovered a particular practical concern is how we can have knowledge of them. I will suggest that knowledge by intuition is plausible but that as things currently stand in moral epistemology it will not provide the unifying ground for nursing. Then I will argue that in the latter approach to definition a certain account of human nature has been advanced in order to provide features that are there to be discovered and so not dependent on human beings for the definition or classification. However, such an attempt to define nursing cannot do what is wanted. Rather than the account of human nature grounding morality and doing so for nursing, the account of human nature itself relies upon a prior account of morality. Because of this it loses its supposed ground of unity for the profession. Nursing is not united by its moral stance especially if this is understood in a strong sense as unique moral stance, but as things currently stand in moral epistemology this is not necessarily a bad thing for practitioners or patients. PMID- 22672681 TI - A reply to 'Phenomenology as research method or substantive metaphysics? An overview of phenomenology's uses in nursing' by Vicki Earle: a phenomenological grapevine? PMID- 22672682 TI - Letter to the editor. PMID- 22672683 TI - Parents need to protect: influences, risks and tensions for parents of prepubertal children born with ambiguous genitalia. AB - AIM AND OBJECTIVES: The aim of the study was to explore parents' experiences of and the influences, risks and tensions associated with their child's genital ambiguity and the place reconstructive surgeries had in their lives. BACKGROUND: Research into the clinical management of disorders of sex development is a complex and growing field of study. A small number of studies have indicated that the decisions parents make with regard to their child's care during infancy are confounded by moral, social and emotional factors which can influence their choices. DESIGN: Narrative methods. METHODS: In-depth interviews elicited stories from 10 mothers and five fathers of 11 prepubertal children. RESULTS: A key theme from the data focused on the parents' motivations to protect their child from the real or perceived threats arising from other people's attitudes and responses to their ambiguous genitalia. Several rationales for their protective behaviours were described, which encouraged the parents to actively manage their child's care. CONCLUSION: The dilemmas that parents face in the complex and challenging situation following the birth of a child with ambiguous genitalia require early support from insightful professionals such as nurses. This support could better prepare the parents to recognise and discuss their protective behaviours and the impact these may have on their child's future. RELEVANCE TO CLINICAL PRACTICE: These findings draw attention to the parents' need for nurses to be knowledgeable about the impact that disorders of sex development can have on family's emotional, psychosocial well-being and decision-making. Nurses' awareness of the debate surrounding genital surgeries is important if they are to understand the motivations that underpin parents' decision-making and how to support them sensitively. Nurses are the health professionals who have the most consistent direct contact with these families throughout the child's life and, therefore, can provide support in the ongoing decision-making process. PMID- 22672684 TI - The use of negative pressure therapy and hyaluronic acid for the management of post-traumatic lower limb injury. AB - Management of severe limb trauma continues to challenge surgeons. Suitable treatment should be individualised for each patient, taking into consideration not only the wound extremity but also the associated injuries, age and socioeconomic status of the patient with the goal to recover function and to improve patient quality of life. The aim of this report is to present a severe degloving multiplane lower limb injury case in which a conservative treatment of the wound was performed with negative pressure therapy and dermal substitute, avoiding amputation and restoring limb function. PMID- 22672686 TI - Effect of incorporation of silane-treated silver and aluminum microparticles on strength and thermal conductivity of PMMA. AB - PURPOSE: The purpose of this study was to study the effect of addition of metal filler particles on different strengths of polymethylmethacrylate (PMMA) and to evaluate the thermal perception in vivo. MATERIALS AND METHODS: The study was carried out in two parts. Part 1 of the study was an in vitro investigation regarding the effect of addition of metal fillers (aluminum and silver) in concentrations of 10%, 20%, and 30%, by volume on the tensile, compressive, and flexural strength of PMMA. Part 2 of the study comprised the clinical evaluation of the thermal perception by 10 edentulous patients provided with two sets of complete dentures, one fabricated with unfilled PMMA and another with 20% aluminum particle filled PMMA on the palatal portion of the maxillary denture. Recorded data were subjected to Student's t-test and ANOVA test. RESULTS: The mean tensile and flexural strength values among control and other groups were found to have statistically significant differences (p < 0.05) except for Al1 and Al2 groups. Mean compressive strength values among control and other groups were statistically significant (p < 0.05). In the clinical study, all 10 participants reported higher perception of hot and cold sensations in dentures with a metalized palatal portion. CONCLUSIONS: Compressive strength increased progressively on increasing the filler concentration for both silver- and aluminum-filled PMMA. Silane-treated metalized PMMA showed reduction in tensile and flexural strength at 30% concentration. Metalized dentures led to an appreciable increase in thermal perception by the participants of this study. PMID- 22672685 TI - The 5'UTR-intron of the Gladiolus polyubiquitin promoter GUBQ1 enhances translation efficiency in Gladiolus and Arabidopsis. AB - BACKGROUND: There are many non-cereal monocots of agronomic, horticultural, and biofuel importance. Successful transformation of these species requires an understanding of factors controlling expression of their genes. Introns have been known to affect both the level and tissue-specific expression of genes in dicots and cereal monocots, but there have been no studies on an intron isolated from a non-cereal monocot. This study characterizes the levels of GUS expression and levels of uidA mRNA that code for beta-glucuronidase (GUS) expression in leaves of Gladiolus and Arabidopsis using GUBQ1, a polyubiquitin promoter with a 1.234 kb intron, isolated from the non-cereal monocot Gladiolus, and an intronless version of this promoter. RESULTS: Gladiolus and Arabidopsis were verified by Southern hybridization to be transformed with the uidA gene that was under control of either the GUBQ1 promoter (1.9 kb), a 5' GUBQ1 promoter missing its 1.234 kb intron (0.68 kb), or the CaMV 35 S promoter. Histochemical staining showed that GUS was expressed throughout leaves and roots of Gladiolus and Arabidopsis with the 1.9 kb GUBQ1 promoter. GUS expression was significantly decreased in Gladiolus and abolished in Arabidopsis when the 5'UTR-intron was absent. In Arabidopsis and Gladiolus, the presence of uidA mRNA was independent of the presence of the 5'UTR-intron. The 5'-UTR intron enhanced translation efficiency for both Gladiolus and Arabidopsis. CONCLUSIONS: The GUBQ1 promoter directs high levels of GUS expression in young leaves of both Gladiolus and Arabidopsis. The 5'UTR-intron from GUBQ1 resulted in a similar pattern of beta glucuronidase translation efficiency for both species even though the intron resulted in different patterns of uidA mRNA accumulation for each species. PMID- 22672687 TI - Recognition of HLA-A*24:137 allele in a Taiwanese unrelated bone marrow stem cell donor and the plausible HLA haplotype associated with A*24:137. AB - We detected a rare HLA-A*24:137 allele in an unrelated Taiwanese haematopoietic stem cell donor during a routine SBT (sequence-based typing) HLA typing exercise. The DNA sequence of A*24:137 is identical to the sequence of A*24:02:01:01 in exons 2 and 3 except at codon 21 where CGC was replaced with CAA. The DNA variation caused an amino acid alteration at amino acid residue 21 (R->Q). The HLA haplotype in association with A*24:137 may be deduced as A*24:137-B*15 DRB1*14. The formation of A*24:137 was probably the result of a nucleotide point mutation involving A*24:02:01:01. It remains to be determined whether A*24:137 is restricted to Taiwanese/Chinese ethnicity. PMID- 22672688 TI - Diaphragmatic hernia in infants following living donor liver transplantation: report of three cases and a review of the literature. AB - DH is a rare complication following LT. This report presents three cases of right sided DH after LT using a left-sided graft. All of the patients were younger than one yr of age, and they were critically ill owing to their original disease, characterized by biliary atresia, progressive familiar intrahepatic cholestasis, and acute liver failure. DH occurred with sudden onset within three months after LT. All of the cases were promptly diagnosed and treated. A literature review of 24 cases of DH identified four factors associated with DH: left-sided graft, right-sided DH, relatively delayed onset of DH, and age-specific chief complaint. DH following LT should be considered as a potential surgical complication when a left-sided graft is used, especially in small infants with coagulopathy and malnutrition. PMID- 22672691 TI - A young infant with multiple red plaques (case presentation). PMID- 22672689 TI - Resting energy expenditure and carbohydrate oxidation are higher in elderly patients with COPD: a case control study. AB - BACKGROUND: Elderly patients with chronic obstructive pulmonary disease (COPD) usually have a compromised nutritional status which is an independent predictor of morbidity and mortality. To know the Resting Energy Expenditure (REE) and the substrate oxidation measurement is essential to prevent these complications. This study aimed to compare the REE, respiratory quotient (RQ) and body composition between patients with and without COPD. METHODS: This case-control study assessed 20 patients with chronic obstructive pulmonary disease attending a pulmonary rehabilitation program. The group of subjects without COPD (control group) consisted of 20 elderly patients attending a university gym, patients of a private service and a public healthy care. Consumption of oxygen (O2) and carbon dioxide (CO2) was determined by indirect calorimetry and used for calculating the resting energy expenditure and respiratory quotient. Body mass index (BMI) and waist circumference (WC) were also measured. Percentage of body fat (%BF), lean mass (kg) and muscle mass (kg) were determined by bioimpedance. The fat free mass index (FFMI) and muscle mass index (MMI) were then calculated. RESULTS: The COPD group had lower BMI than control (p = 0.02). However, WC, % BF, FFMI and MM-I did not differ between the groups. The COPD group had greater RQ (p = 0.01), REE (p = 0.009) and carbohydrate oxidation (p = 0.002). CONCLUSIONS: Elderly patients with COPD had higher REE, RQ and carbohydrate oxidation than controls. PMID- 22672692 TI - A newborn infant with sepsis-like clinical picture and petechial bleeding (case presentation). PMID- 22672693 TI - Editors' comments. PMID- 22672696 TI - Improved knee flexion following high-flexion total knee arthroplasty. AB - BACKGROUND: The application of new techniques and materials in total knee arthroplasty (TKA) continue to be a primary focus in orthopedic surgery. The primary aim of the present study is to evaluate post TKA total range of motion (ROM) among a group of patients who received a gender specific high-flexion design modification implant compared to a control group of patients who received non-gender specific implants. METHODS AND RESULTS: The control group was comprised of 39 TKAs that were recruited pre-operatively and received the non gender specific implant while the study group consisted of 39 TKAs who received gender specific implants. The study group yielded an improvement in mean post operative ROM of 21 degrees at 12 months, whereas the mean improvement in ROM among the control group was 11 degrees . Thus, the study group had a 10 degrees increased ROM improvement (91%) over the control group (p = 0.00060). In addition, 100% of the subjects with gender specific high-flexion implants achieved greater or equal ROM post-operatively compared to 82% for the control cohort. Lastly, women who exhibited greater pre-operative ROM and lower body mass index (BMI) were found to benefit the most with the gender specific prosthesis. CONCLUSION: Our study demonstrates that among subjects with a normal BMI, the gender specific high-flexion knee implant is associated with increased ROM as compared to the non-gender specific non-high-flexion implant designs. PMID- 22672697 TI - Risk factors, healthcare-seeking and sexual behaviour among patients with genital ulcers in Zambia. AB - BACKGROUND: Genital ulcers (GU) are associated with an increased risk of HIV transmission. Understanding risk factors for genital ulcers and sexual behaviour patterns after onset of symptoms and health seeking behaviour among GU-patients can provide useful information to aid design effective prevention strategies for genital ulcers. We investigated risk factors of self-reported GUs and care seeking in the general population, and assessed GU patients regarding past care seeking, recent sexual behaviour and partner awareness of the disease. METHODS: We analysed national data on genital ulcers from the 2007 Zambia Demographic and Health Survey, and data from a cross-sectional survey of genital ulcer patients from primary health care facilities in Lusaka, Zambia. RESULTS: The prevalence of GU in 2007 in the general population of Lusaka was 3.6%. Important predictors for genital ulcers were age 25-29 years, being widowed/separated/divorced and having a high number of life-time sexual partners. No differences in care-seeking were observed by residence, wealth and gender, and 60% of the respondents sought care from public health facilities. Among patients with GUs in Lusaka, 14% sought care >2 weeks after symptom onset. Forty-two percent were not aware of their HIV status, 57% reported sex after onset of symptoms and only 15% reported consistent condom use. CONCLUSIONS: Low awareness of HIV status despite high probability of being infected and low condom use after onset of genital ulcer symptoms leads to a high potential for transmission to sexual partners. This, combined with the fact that many patients with GUs delayed seeking care, shows a need for awareness campaigns about GUs and the importance of abstinence or use of condoms when experiencing such symptoms. PMID- 22672698 TI - Increased stroke risk in Bell's palsy patients without steroid treatment. AB - BACKGROUND AND PURPOSE: To investigate the risk of stroke development following a diagnosis of Bell's palsy in a nationwide follow-up study. METHODS AND MATERIALS: Information on Bell's palsy and other factors relevant for stroke was obtained for 433218 eligible subjects without previous stroke who had ambulatory visit in 2004. Of those, 897 patients with Bell's palsy were identified. Over a median 2.9 years of follow-up, 4581 incident strokes were identified. We estimated hazard ratios (HR) and 95% confidence intervals [CI] with Cox proportional hazard models adjusting for age, sex, co-morbidities, and important risk factors. Standardized incidence ratio of stroke amongst patients with Bell's palsy was analyzed. RESULTS: Compared with non-Bell's palsy patients, patients with Bell's palsy had a 2.02-times (95% CI, 1.42-2.86) higher risk of stroke. The adjusted HR of developing stroke for patients with Bell's palsy treated with and without systemic steroid were 1.67 (95% CI, 0.69-4) and 2.10 (95%, 1.40-3.07), respectively. CONCLUSIONS: Patients with Bell's palsy carry a higher risk of stroke than the general population. Our data suggest that these patients might benefit from a more intensive stroke prevention therapy and regular follow-up after initial diagnosis. PMID- 22672700 TI - Infection complications in an unselected cohort of patients with multiple myeloma treated with lenalidomide combinations. PMID- 22672699 TI - Detection of identity by descent using next-generation whole genome sequencing data. AB - BACKGROUND: Identity by descent (IBD) has played a fundamental role in the discovery of genetic loci underlying human diseases. Both pedigree-based and population-based linkage analyses rely on estimating recent IBD, and evidence of ancient IBD can be used to detect population structure in genetic association studies. Various methods for detecting IBD, including those implemented in the soft- ware programs fastIBD and GERMLINE, have been developed in the past several years using population genotype data from microarray platforms. Now, next generation DNA sequencing data is becoming increasingly available, enabling the comprehensive analysis of genomes, in- cluding identifying rare variants. These sequencing data may provide an opportunity to detect IBD with higher resolution than previously possible, potentially enabling the detection of disease causing loci that were previously undetectable with sparser genetic data. RESULTS: Here, we investigate how different levels of variant coverage in sequencing and microarray genotype data influences the resolution at which IBD can be detected. This includes microarray genotype data from the WTCCC study, denser genotype data from the HapMap Project, low coverage sequencing data from the 1000 Genomes Project, and deep coverage complete genome data from our own projects. With high power (78%), we can detect segments of length 0.4 cM or larger using fastIBD and GERMLINE in sequencing data. This compares to similar power to detect segments of length 1.0 cM or higher with microarray genotype data. We find that GERMLINE has slightly higher power than fastIBD for detecting IBD segments using sequencing data, but also has a much higher false positive rate. CONCLUSION: We further quantify the effect of variant density, conditional on genetic map length, on the power to resolve IBD segments. These investigations into IBD resolution may help guide the design of future next generation sequencing studies that utilize IBD, including family-based association studies, association studies in admixed populations, and homozygosity mapping studies. PMID- 22672701 TI - Protoanemonin: a natural quorum sensing inhibitor that selectively activates iron starvation response. AB - Many Gram-negative bacteria employ cell-to-cell communication mediated by N-acyl homoserine lactones (quorum sensing) to control expression of a wide range of genes including, but not limited to, genes encoding virulence factors. Outside the laboratory, the bacteria live in complex communities where signals may be perceived across species. We here present a newly found natural quorum sensing inhibitor, produced by the pseudomonads Pseudomonas sp. B13 and Pseudomonas reinekei MT1 as a blind end in the biodegradation of organochloride xenobiotics, which inhibits quorum sensing in P. aeruginosa in naturally occurring concentrations. This catabolite, 4-methylenebut-2-en-4-olide, also known as protoanemonin, has been reported to possess antibacterial properties, but seems to have dual functions. Using transcriptomics and proteomics, we found that protoanemonin significantly reduced expression of genes and secretion of proteins known to be under control of quorum sensing in P. aeruginosa. Moreover, we found activation of genes and gene products involved in iron starvation response. It is thus likely that inhibition of quorum sensing, as the production of antibiotics, is a phenomenon found in complex bacterial communities. PMID- 22672702 TI - Should mortality be informed for cesarean hysterectomy for placenta accreta? PMID- 22672703 TI - Immunohistochemical phenotyping of the inflammatory infiltrate in de novo autoimmune hepatitis after liver transplantation in children. AB - We have investigated the inflammatory infiltrate in post-transplant dn-AIH, a form of late insidious graft rejection, focusing on transcription factors defining effector and T-regs, using an antigen retrieval immunohistochemical method on archived liver tissue, and compared it with ACR and classical AIH. Paraffin-embedded liver biopsies from pediatric patients with dn-AIH (n = 10), ACR (n = 10), and AIH (n = 13) were selected randomly and stained using antibodies directed to CD4, CD8, T-bet (marker of Th1 polarization), GATA-3 (marker of Th2 polarization), FOXP3 (marker for T regulatory cells), IL-17, CD56 (NK cells), and perforin. Portal and lobular lymphocytic infiltrate was assessed semi-quantitatively. Prominent CD4, CD8, and T-bet positivity were present in both the lobular and portal infiltrate of all three conditions. Overall T-bet score of lobular inflammation in the dn-AIH group was lower than in the ACR and AIH groups (p = 0.02). In contrast, most samples showed absent or minimal GATA-3 positivity. FOXP3, CD56, IL-17, and perforin staining of mild to moderate severity were present in all three groups in both the portal and lobular infiltrate. A Th1 polarization of the inflammatory infiltrate characterizes dn AIH, but also ACR and AIH. PMID- 22672704 TI - Effects of health literacy to self-efficacy and preventive care utilization among older adults. AB - AIM: This study examined the relationships between health literacy, self-efficacy and preventive care utilization among older adults in Taiwan. METHODS: The data were from a longitudinal survey, "Taiwan Longitudinal Study in Aging" in 2003 and 2007. A total of 3479 participants who completed both two waves were included for analysis. Health literacy first was constructed through education, cognitive function and disease knowledge through structural equation modeling (SEM); then, the associations of health literacy to later self-efficacy and preventive care were examined. RESULTS: The model fit of SEM was good, indicating that the construct of health literacy was appropriate. Healthy literacy showed a moderate positive effect on self-efficacy and a small positive effect on preventive care utilization. CONCLUSIONS: Health literacy increases self-efficacy and utilization of preventive care. Promoting people's health knowledge and health literacy is suggested. PMID- 22672706 TI - Fungal microflora of the skin and their role in biofilm infection. PMID- 22672705 TI - Coculture with hematopoietic stem cells protects cardiomyocytes against apoptosis via paracrine activation of AKT. AB - BACKGROUND: Previous experimental studies concluded that stem cells (SC) may exert their beneficial effects on the ischemic heart by paracrine activation of antiapoptotic pathways. In order to identify potential cardioprotective mediators, we performed a systematic analysis of the differential gene expression of hematopoietic SC after coculture with cardiomyocytes (CM). METHODS: After 48 h of coculture with neonatal rat ventricular CM (NRVCM), two consecutive cell sorting steps generated a highly purified population of conditioned murine hematopoietic SC (>99%). Next, a genome-wide microarray analysis of cocultured vs. monocultured hematopoietic SC derived from three independent experiments was performed. The analysis of differentially expressed genes was focused on products that are secretable and/or membrane-bound and potentially involved in antiapoptotic signalling. RESULTS: We found CCL-12, Macrophage Inhibitory Factor, Fibronectin and connexin 40 significantly upregulated in our coculture model. An ELISA of cell culture supernatants was performed to confirm secretion of candidate genes and showed that coculture supernatants revealed markedly higher CCL-12 concentrations. Moreover, we stimulated NRVCM with concentrated coculture supernatants which resulted in a significant reduction of apoptosis compared to monoculture-derived supernatant. Mechanistically, NRVCMs stimulated with coculture supernatants showed a higher level of AKT-phosphorylation, consistent with enhanced antiapoptotic signaling. CONCLUSION: In summary, our results show that the interaction between hematopoietic SC and NRVCM led to a modified gene expression and induction of antiapoptotic pathways. These findings may thus at least in part explain the cardioprotective effects of hematopoietic SC. PMID- 22672707 TI - Lipoprotein particle distribution and skeletal muscle lipoprotein lipase activity after acute exercise. AB - BACKGROUND: Many of the metabolic effects of exercise are due to the most recent exercise session. With recent advances in nuclear magnetic resonance spectroscopy (NMRS), it is possible to gain insight about which lipoprotein particles are responsible for mediating exercise effects. METHODS: Using a randomized cross over design, very low density lipoprotein (VLDL) responses were evaluated in eight men on the morning after i) an inactive control trial (CON), ii) exercising vigorously on the prior evening for 100 min followed by fasting overnight to maintain an energy and carbohydrate deficit (EX-DEF), and iii) after the same exercise session followed by carbohydrate intake to restore muscle glycogen and carbohydrate balance (EX-BAL). RESULTS: The intermediate, low and high density lipoprotein particle concentrations did not differ between trials. Fasting triglyceride (TG) determined biochemically, and mean VLDL size were lower in EX DEF but not in EX-BAL compared to CON, primarily due to a reduction in VLDL-TG in the 70-120 nm (large) particle range. In contrast, VLDL-TG was lower in both EX DEF and EX-BAL compared to CON in the 43-55 nm (medium) particle range. VLDL-TG in smaller particles (29-43 nm) was unaffected by exercise. Because the majority of VLDL particles were in this smallest size range and resistant to change, total VLDL particle concentration was not different between any of these conditions. Skeletal muscle lipoprotein lipase (LPL) activity was also not different across these 3 trials. However, in CON only, the inter-individual differences in LPL activity were inversely correlated with fasting TG, VLDL-TG, total, large and small VLDL particle concentration and VLDL size, indicating a regulatory role for LPL in the non-exercised state. CONCLUSIONS: These findings reveal a high level of differential regulation between different sized triglyceride-rich lipoproteins following exercise and feeding, in the absence of changes in LPL activity. PMID- 22672708 TI - Cell division and density of symbiotic Chlorella variabilis of the ciliate Paramecium bursaria is controlled by the host's nutritional conditions during early infection process. AB - The association of ciliate Paramecium bursaria with symbiotic Chlorella sp. is a mutualistic symbiosis. However, both the alga-free paramecia and symbiotic algae can still grow independently and can be reinfected experimentally by mixing them. Effects of the host's nutritional conditions against the symbiotic algal cell division and density were examined during early reinfection. Transmission electron microscopy revealed that algal cell division starts 24 h after mixing with alga-free P. bursaria, and that the algal mother cell wall is discarded from the perialgal vacuole membrane, which encloses symbiotic alga. Labelling of the mother cell wall with Calcofluor White Stain, a cell-wall-specific fluorochrome, was used to show whether alga had divided or not. Pulse labelling of alga-free P. bursaria cells with Calcofluor White Stain-stained algae with or without food bacteria for P. bursaria revealed that the fluorescence of Calcofluor White Stain in P. bursaria with bacteria disappeared within 3 days after mixing, significantly faster than without bacteria. Similar results were obtained both under constant light and dark conditions. This report is the first describing that the cell division and density of symbiotic algae of P. bursaria are controlled by the host's nutritional conditions during early infection. PMID- 22672709 TI - Carbon and nitrogen partitioning during the post-anthesis period is conditioned by N fertilisation and sink strength in three cereals. AB - Further knowledge of the processes conditioning nitrogen use efficiency (NUE) is of great relevance to crop productivity. The aim of this paper was characterise C and N partitioning during grain filling and their implications for NUE. Cereals such as bread wheat (Triticum aestivum L. cv Califa sur), triticale (* Triticosecale Wittmack cv. Imperioso) and tritordeum (* Tritordeum Asch. & Graebn line HT 621) were grown under low (LN, 5 mm NH(4) NO(3)) and high (HN, 15 mm NH(4)NO(3)) N conditions. We conducted simultaneous double labelling ((12)CO(2) and (15)NH(4) (15)NO(3)) in order to characterise C and N partitioning during grain filling. Although triticale plants showed the largest total and ear dry matter values in HN conditions, the large investment in shoot and root biomass negatively affected ear NUE. Tritordeum was the only genotype that increased NUE in both N treatments (NUE(total)), whereas in wheat, no significant effect was detected. N labelling revealed that N fertilisation during post-anthesis was more relevant for wheat and tritordeum grain filling than for triticale. The study also revealed that the investments of C and N in flag leaves and shoots, together with the 'waste' of photoassimilates in respiration, conditioned the NUE of plants, and especially under LN. These results suggest that C and N use by these plants needs to be improved in order to increase ear C and N sinks, especially under LN. It is also remarkable that even though tritordeum shows the largest increase in NUE, the low yield of this cereal limits its agronomic value. PMID- 22672710 TI - How orthodox protestant parents decide on the vaccination of their children: a qualitative study. AB - BACKGROUND: Despite high vaccination coverage, there have recently been epidemics of vaccine preventable diseases in the Netherlands, largely confined to an orthodox protestant minority with religious objections to vaccination. The orthodox protestant minority consists of various denominations with either low, intermediate or high vaccination coverage. All orthodox protestant denominations leave the final decision to vaccinate or not up to their individual members. METHODS: To gain insight into how orthodox protestant parents decide on vaccination, what arguments they use, and the consequences of their decisions, we conducted an in-depth interview study of both vaccinating and non-vaccinating orthodox protestant parents selected via purposeful sampling. The interviews were thematically coded by two analysts using the software program Atlas.ti. The initial coding results were reviewed, discussed, and refined by the analysts until consensus was reached. Emerging concepts were assessed for consistency using the constant comparative method from grounded theory. RESULTS: After 27 interviews, data saturation was reached. Based on characteristics of the decision making process (tradition vs. deliberation) and outcome (vaccinate or not), 4 subgroups of parents could be distinguished: traditionally non-vaccinating parents, deliberately non-vaccinating parents, deliberately vaccinating parents, and traditionally vaccinating parents. Except for the traditionally vaccinating parents, all used predominantly religious arguments to justify their vaccination decisions. Also with the exception of the traditionally vaccinating parents, all reported facing fears that they had made the wrong decision. This fear was most tangible among the deliberately vaccinating parents who thought they might be punished immediately by God for vaccinating their children and interpreted any side effects as a sign to stop vaccinating. CONCLUSIONS: Policy makers and health care professionals should stimulate orthodox protestant parents to make a deliberate vaccination choice but also realize that a deliberate choice does not necessarily mean a choice to vaccinate. PMID- 22672711 TI - Does outdoor air pollution induce new cases of asthma? Biological plausibility and evidence; a review. AB - It is widely accepted that air pollution can exacerbate asthma in those who already have the condition. What is less clear is whether air pollution can contribute to the initiation of new cases of asthma. Mechanistic evidence from toxicological studies, together with recent information on genes that predispose towards the development of asthma, suggests that this is biologically plausible, particularly in the light of the current understanding of asthma as a complex disease with a variety of phenotypes. The epidemiological evidence for associations between ambient levels of air pollutants and asthma prevalence at a whole community level is unconvincing; meta-analysis confirms a lack of association. In contrast, a meta-analysis of cohort studies found an association between asthma incidence and within-community variations in air pollution (largely traffic dominated). Similarly, a systematic review suggests an association of asthma prevalence with exposure to traffic, although only in those living very close to heavily trafficked roads carrying a lot of trucks. Based on this evidence, the U.K.'s Committee on the Medical Effects of Air Pollutants recently concluded that, overall, the evidence is consistent with the possibility that outdoor air pollution might play a role in causing asthma in susceptible individuals living very close to busy roads carrying a lot of truck traffic. Nonetheless, the effect on public health is unlikely to be large: air pollutants are likely to make only a small contribution, compared with other factors, in the development of asthma, and in only a small proportion of the population. PMID- 22672712 TI - Mandibular molar rehabilitation using orthodontic extrusion associated with odontoplasty. AB - The aim of this clinical report is to describe the successful treatment of a mandibular first molar presenting an extensive fracture at the buccal aspect in a young patient. The extension of the fracture was a negative prognostic factor for tooth maintenance. An alternative clinical treatment was proposed since the patient was young and presented with good oral hygiene and periodontal health. The treatment was based on orthodontic forced eruption associated with odontoplasty. A 3-year follow-up after the surgical procedure demonstrated the maintenance of periodontal health and good plaque control. It can be concluded that orthodontic forced eruption associated with odontoplasty promoted favorable conditions for prosthetic rehabilitation and is a feasible procedure in the treatment of tooth fracture extended below the cementoenamel junction. PMID- 22672713 TI - Clinical and radiological outcomes of two implants with different prosthetic interfaces and neck configurations: randomized, controlled, split-mouth clinical trial. AB - BACKGROUND: Peri-implant bone loss seems to occur following implant placement/loading regardless of all the efforts to eliminate it. Several factors, including surgical trauma, biologic width establishment, lack of passive fit of the superstructures, implant-abutment microgap, and occlusal overloading, may increase peri-implant bone loss. Over the years, new interface designs were introduced and clinical studies suggest that internal conical connection and platform shifting may be advantageous for marginal bone preservation. PURPOSE: To compare clinical and radiological outcomes of two implant designs with different prosthetic interfaces and neck configurations in a randomized, controlled, split mouth clinical trial. MATERIALS AND METHODS: Thirty-four partially edentate patients randomly received at least one internal conical connection with back tapered collar and platform shifting design or external-hexagon implants with flat-to-flat implant-abutment interface. Primary end point was peri-implant bone level changes at different time points, failures of implants and/or prosthesis, any complications, implant stability quotient (ISQ) values, and periodontal parameters. RESULTS: No dropout occurred. Marginal bone changes were statistically significantly different with better results for the internal conical connection. No implants and prosthesis failures have been observed, yielding a cumulative survival rate of 100%. A high ISQ value was found for both implants, and no statistically significant difference was found for ISQ mean values between interventions at each time point (p > .05). All implants showed no bleeding on probing and a very slight amount of plaque at the 1-year-in-function visit. CONCLUSIONS: Both implant designs investigated performed similarly in terms of failure rates, providing successful results up to 1 year after loading. The back-tapered neck configuration with conical connection and built-in platform shifting showed statistically lower marginal bone loss than straight neck configuration with flat-to-flat implant-abutment interface and external-hexagonal connection. PMID- 22672715 TI - Understanding acute care nurse practitioner communication and decision-making in healthcare teams. AB - AIMS AND OBJECTIVES: This paper aims to describe communication and decision making in healthcare teams following the introduction of an acute care nurse practitioner role. BACKGROUND: Healthcare teams need to establish clear processes for communication and decision-making about patient care to be effective. Little is known about how acute care nurse practitioners affect these team processes. DESIGN: Observational/descriptive study. METHODS: Structured non-participant observations of acute care nurse practitioners and healthcare team members during routine patient care activities were completed to identify the verbal and non verbal behaviours. Data were collected in two hospitals in one Canadian province from March-May 2009 for a total of 17 hours and 23 minutes. Descriptive statistics were generated. RESULTS: Differences in communication and decision making were noted between the cases. The acute care nurse practitioners in Case 1 spoke most frequently with physicians when making patient care decisions while the acute care nurse practitioners in Case 2 spoke most frequently with the nurses. The acute care nurse practitioners needed to validate all patient care decisions if prescriptive authority had not been transferred to them. DISCUSSION: Much of the potential of acute care nurse practitioner roles rests on the ability to enact the full scope of their role. Acute care nurse practitioner scope of practice depends on the legislation, the transfer of decision-making authority in the organisation, and the messages received form the medical and nursing leadership group. CONCLUSIONS: This appears to be the first in-depth description of communication and decision-making in healthcare teams following the introduction of acute care nurse practitioners and furthers our understanding of how system-level imperatives filter down to healthcare teams. RELEVANCE TO CLINICAL PRACTICE: The transfer of prescriptive authority to acute care nurse practitioners affected communication and decision-making and changed the way routine activities were conducted. PMID- 22672714 TI - In silico polymorphism analysis for the development of simple sequence repeat and transposon markers and construction of linkage map in cultivated peanut. AB - BACKGROUND: Peanut (Arachis hypogaea) is an autogamous allotetraploid legume (2n = 4x = 40) that is widely cultivated as a food and oil crop. More than 6,000 DNA markers have been developed in Arachis spp., but high-density linkage maps useful for genetics, genomics, and breeding have not been constructed due to extremely low genetic diversity. Polymorphic marker loci are useful for the construction of such high-density linkage maps. The present study used in silico analysis to develop simple sequence repeat-based and transposon-based markers. RESULTS: The use of in silico analysis increased the efficiency of polymorphic marker development by more than 3-fold. In total, 926 (34.2%) of 2,702 markers showed polymorphisms between parental lines of the mapping population. Linkage analysis of the 926 markers along with 253 polymorphic markers selected from 4,449 published markers generated 21 linkage groups covering 2,166.4 cM with 1,114 loci. Based on the map thus produced, 23 quantitative trait loci (QTLs) for 15 agronomical traits were detected. Another linkage map with 326 loci was also constructed and revealed a relationship between the genotypes of the FAD2 genes and the ratio of oleic/linoleic acid in peanut seed. CONCLUSIONS: In silico analysis of polymorphisms increased the efficiency of polymorphic marker development, and contributed to the construction of high-density linkage maps in cultivated peanut. The resultant maps were applicable to QTL analysis. Marker subsets and linkage maps developed in this study should be useful for genetics, genomics, and breeding in Arachis. The data are available at the Kazusa DNA Marker Database (http://marker.kazusa.or.jp). PMID- 22672716 TI - Gene expression in the developing aleurone and starchy endosperm of wheat. AB - Wheat is a critical food source globally. Food security is an increasing concern; current production levels are not expected to keep pace with global demand. New technologies have provided a vast array of wheat genetic data; however, best use of this data requires placing it within a framework in which the various genes, pathways and interactions can be examined. Here we present the first systematic comparison of the global transcriptomes of the aleurone and starchy endosperm of the developing wheat seed (Triticum aestivum), at time points critical to the development of the aleurone layer; 6-, 9- and 14-day post-anthesis. Illumina sequencing gave 25-55 million sequence reads per tissue, of the trimmed reads, 70%-81% mapped to reference expressed sequence transcripts. Transcript abundance was analysed by performing RNA-Seq normalization to generate reads per kilobase of exon model per million mapped reads values, and these were used in comparative analyses between the tissues at each time point using Kal's Z-test. This identified 9414-13 202 highly differentially expressed transcripts that were categorized on the basis of tissue and time point expression and functionally analysed revealing two very distinct tissues. The results demonstrate the fundamental biological reprogramming of the two major biologically and economically significant tissues of the wheat seed over this time course. Understanding these changes in gene expression profiles is essential to mining the potential these tissues hold for human nutrition and contributing to the systems biology of this important crop plant. PMID- 22672717 TI - Bladder endometriosis developed after long-term estrogen therapy for prostate cancer. PMID- 22672718 TI - Age- and weight-adjusted warfarin initiation nomogram for ischaemic stroke patients. AB - OBJECTIVES: Specific guidelines for initial dosing of warfarin in ischaemic stroke patients have not been developed. Therefore, we have developed an age- and weight-adjusted warfarin initiation nomogram (AW-WIN) for ischaemic stroke patients and then evaluated the efficacy and safety of AW-WIN compared with physician-determined warfarin dosing (PDWD). METHODS: The age- and weight adjusted warfarin initiation nomogram was administered to 104 acute ischaemic stroke patients between January 2008 and February 2009. A historical control group (PDWD) of 96 patients was selected from comparable patients who were discharged with warfarin during the previous year. Time-to-therapeutic international normalized ratios (INRs) and the incidence of excessive anticoagulation were compared in the AW-WIN and PDWD groups. RESULTS: The general characteristics, risk factors, and stroke mechanism of the AW-WIN and PDWD groups did not differ significantly. The mean time to INR >= 2.0 was significantly shorter in the AW-WIN than in the PDWD group (4.9 +/- 0.7 vs. 6.2 +/- 0.8 days, P = 0.0008). After adjustment for potential confounding variables, the AW-WIN group reached target INR faster than the PDWD group (hazard ratio, 1.76; 95% confidence interval, 1.26-2.45; P = 0.001). The time-to-therapeutic INR >=1.7 was shorter (P = 0.0002), the proportion of patients with therapeutic INR (2-3) at 5 days was higher (P = 0.002), and the rate of excessive anticoagulation of >=3.5 INR during hospitalization was lower (P = 0.024) in the AW-WIN than in the PDWD group. CONCLUSIONS: AW-WIN reduces the time to target INR and the risk of excessive anticoagulation. AW-WIN may be an efficient and safe method of anticoagulation during the acute phase of ischaemic stroke. PMID- 22672719 TI - Technical aspects of single-port thoracoscopic surgery for lobectomy. AB - Thoracoscopic Surgery is in common use in routine surgical practice. With the advancement of the various techniques and instruments required, mini wounds and fewer thoracoports become practical in recent years. Here, we report our experience of performing lobectomy with radical lymph node dissection in 3 patients using regular straight endoscopic instruments. We demonstrate the feasibility of such techniques and discuss the key points of effectively performing the procedures. Because of the favorable outcomes, we encourage such procedures to be widely applied in surgical operations of various types. PMID- 22672721 TI - Bioactive oligopeptides in dermatology: Part II. AB - Peptides are central to the regulation and modulation of the chemical reactions and biological responses that occur in nature. Many physiological processes are affected by the interactions of these peptides, including cell proliferation and migration, inflammation, melanogenesis, angiogenesis and innate immunity. Thus, biologically active peptides offer a great potential medically and therapeutically. Moreover, the ability to generate synthetic peptides with attention to specifically modulating their pharmacokinetics and properties for increased potency, delivery and stability has spurred much interest in this rapidly growing field of research. In this review, we focus on the therapeutic uses of bioactive peptides as antimicrobials and effectors of neurotransmitter release. We also highlight the advantages and challenges associated with this new technology and discuss methods for improving oligopeptide transdermal delivery. PMID- 22672720 TI - Fine-scale genetic breaks driven by historical range dynamics and ongoing density barrier effects in the estuarine seaweed Fucus ceranoides L. AB - BACKGROUND: Factors promoting the emergence of sharp phylogeographic breaks include restricted dispersal, habitat discontinuity, physical barriers, disruptive selection, mating incompatibility, genetic surfing and secondary contact. Disentangling the role of each in any particular system can be difficult, especially when species are evenly distributed across transition zones and dispersal barriers are not evident. The estuarine seaweed Fucus ceranoides provides a good example of highly differentiated populations along its most persistent distributional range at the present rear edge of the species distribution, in NW Iberia. Intrinsic dispersal restrictions are obvious in this species, but have not prevented F. ceranoides from vastly expanding its range northwards following the last glaciation, implying that additional factors are responsible for the lack of connectivity between neighbouring southern populations. In this study we analyze 22 consecutive populations of F. ceranoides along NW Iberia to investigate the processes generating and maintaining the observed high levels of regional genetic divergence. RESULTS: Variation at seven microsatellite loci and at mtDNA spacer sequences was concordant in revealing that Iberian F. ceranoides is composed of three divergent genetic clusters displaying nearly disjunct geographical distributions. Structure and AFC analyses detected two populations with an admixed nuclear background. Haplotypic diversity was high in the W sector and very low in the N sector. Within each genetic cluster, population structure was also pervasive, although shallower. CONCLUSIONS: The deep divergence between sectors coupled with the lack of support for a role of oceanographic barriers in defining the location of breaks suggested 1) that the parapatric genetic sectors result from the regional reassembly of formerly vicariant sub-populations, and 2) that the genetic discontinuities at secondary contact zones (and elsewhere) are maintained despite normal migration rates. We conclude that colonization and immigration, as sources of gene-flow, have very different genetic effects. Migration between established populations is effectively too low to prevent their differentiation by drift or to smooth historical differences inherited from the colonization process. F. ceranoides, but possibly low-dispersal species in general, appear to be unified to a large extent by historical, non-equilibrium processes of extinction and colonization, rather than by contemporary patterns of gene flow. PMID- 22672722 TI - Evaluation of pretransplant factors predicting cardiac dysfunction following high dose melphalan conditioning and autologous peripheral blood stem cell transplantation. AB - BACKGROUND: Cardiac complications following hematopoietic stem cell transplantation (HSCT) are emerging as a significant concern given the increasing utilization of HSCT for a variety of hematologic malignancies. METHODS: We utilized an existing database to determine the frequency of cardiac dysfunction (CD), namely a decrease in left ventricular ejection fraction, following conditioning with high-dose melphalan (HDM) and autologous HSCT for multiple myeloma (MM) and systemic amyloidosis (AL). We then performed a case-control study to examine variables associated with increased risk of CD in this population. RESULTS: In MM patients undergoing HSCT, the rate of CD was 1.6% (17/1050, 95% CI: [0.9, 2.6]). None of the examined pre-HSCT variables or HDM dose were significantly associated with development of CD in this population. In patients with AL, the rate of CD was 5.6% (24/426, 95% CI: [3.6, 8.3]). On univariate analysis, decision to administer an HDM dose <200 mg/m(2) [odds ratio (OR): 4.59 (1.27-16.57) P = 0.02], pretransplant left ventricular ejection fraction <60% [OR: 17.78 (2.29-138.33) P = 0.006], and documented amyloid involvement of >= 3 organs [OR: 4.0 (1.03-15.6) P = 0.046] were associated with the development of CD in the AL population. No other examined peri-transplant factors were associated with development of CD. CONCLUSION: To our knowledge, this is the first series to report a significant rate of CD following HDM conditioning and autologous HSCT in patients with AL. PMID- 22672723 TI - Energetic and conformational changes upon complexation of gelatin with sodium dodecyl sulfate. AB - The interaction between gelatin and sodium dodecyl sulfate (SDS) is investigated by calorimetry and photometric spectrum. The conformational change in gelatin chains upon binding of SDS, the morphology development of gelatin-SDS complex, and the nature of the interaction are studied by isothermal titration calorimetry (ITC), circular dichroism (CD), fluorescence, and freeze-fracture transmission electronic microscope micrograph (FF-TEM). The results show that the exothermic binding process is driven by both electrostatic and hydrophobic interaction. The triple helix structure of gelatin is decomposed to random coil upon the binding of SDS. The morphology of complex transfers from branch-like to "necklace-and bead". The interaction can be controlled by the concentration of SDS, the pH value of the solution, and the ionic strength of the system. PMID- 22672724 TI - Cognitive impairments and functional declines in older adults at high risk for care needs. AB - AIM: Functional status of those who have very mild cognitive impairment have not been sufficiently investigated. In the current study, we analyzed the characteristics of functional awareness in older adults who had cognitive impairment and were at high risk of requiring support/care (termed as specified elderly at high risk for care needs in the long-term care insurance scheme). METHODS: The answers of a health check, which is provided by the local municipal government for those aged 75 years or older who have not been certified as eligible for care services, were analyzed. The differences of the variables between the two groups regarding yes/no answers to each of three cognition related questions were analyzed. Then, a multiple logistic analysis was carried out to investigate the association of yes/no answers of the three cognition related questions and the awareness of functional decline. RESULTS: The participants who had cognitive impairment had greater awareness of functional declines. Multiple logistic regression analysis showed that subjective memory impairment and disorientation were significantly associated with a wider range of awareness of functional decline. CONCLUSIONS: Subjective cognitive impairment was associated with a wide range of awareness of functional decline in older adults at high risk for care need. PMID- 22672725 TI - Postprandial leucine and insulin responses and toxicological effects of a novel whey protein hydrolysate-based supplement in rats. AB - The purpose of this study was: aim 1) compare insulin and leucine serum responses after feeding a novel hydrolyzed whey protein (WPH)-based supplement versus a whey protein isolate (WPI) in rats during the post-absorptive state, and aim 2) to perform a thorough toxicological analysis on rats that consume different doses of the novel WPH-based supplement over a 30-day period. In male Wistar rats (~250 g, n = 40), serum insulin and leucine concentrations were quantified up to 120 min after one human equivalent dose of a WPI or the WPH based supplement. In a second cohort of rats (~250 g, n = 20), we examined serum/blood and liver/kidney histopathological markers after 30 days of feeding low (1human equivalent dose), medium (3 doses) and high (6 doses) amounts of the WPH-based supplement. In aim 1, higher leucine levels existed at 15 min after WPH vs. WPI ingestion (p = 0.04) followed by higher insulin concentrations at 60 min (p = 0.002). In aim 2, liver and kidney histopathology/toxicology markers were not different 30 days after feeding with low, medium, high dose WPH-based supplementation or water only. There were no between-condition differences in body fat or lean mass or circulating clinical chemistry markers following the 30 day feeding intervention in aim 2. In comparison to WPI, acute ingestion of a novel WPH-based supplement resulted in a higher transient leucine response with a sequential increase in insulin. Furthermore, chronic ingestion of the tested whey protein hydrolysate supplement appears safe. PMID- 22672726 TI - Post-transcriptional regulation on a global scale: form and function of Csr/Rsm systems. AB - Originally described as a repressor of gene expression in the stationary phase of growth, CsrA (RsmA) regulates primary and secondary metabolic pathways, biofilm formation, motility, virulence circuitry of pathogens, quorum sensing and stress response systems by binding to conserved sequences in its target mRNAs and altering their translation and/or turnover. While the binding of CsrA to RNA is understood at an atomic level, new mechanisms of gene activation and repression by this protein are still emerging. In the gamma-proteobacteria, small non-coding RNAs (sRNAs) use molecular mimicry to sequester multiple CsrA dimers away from mRNA. In contrast, the FliW protein of Bacillus subtilis inhibits CsrA activity by binding to this protein, thereby establishing a checkpoint in flagellum morphogenesis. Turnover of CsrB and CsrC sRNAs in Escherichia coli requires a specificity protein of the GGDEF-EAL domain superfamily, CsrD, in addition to the housekeeping nucleases RNase E and PNPase. The Csr system of E. coli contains extensive autoregulatory circuitry, which governs the expression and activity of CsrA. Interaction of the Csr system with transcriptional regulatory networks results in a variety of complex response patterns. This minireview will highlight basic principles and new insights into the workings of these complex eubacterial regulatory systems. PMID- 22672727 TI - Can echocardiographic particle image velocimetry correctly detect motion patterns as they occur in blood inside heart chambers? A validation study using moving phantoms. AB - AIMS: To validate Echo Particle Image Velocimetry (PIV) METHODS: High fidelity string and rotating phantoms moving with different speed patterns were imaged with different high-end ultrasound systems at varying insonation angles and frame rates. Images were analyzed for velocity and direction and for complex motion patterns of blood flow with dedicated software. Post-processing was done with MATLAB-based tools (Dflow, JUV, University Leuven). RESULTS: Velocity estimation was accurate up to a velocity of 42 cm/s (r = 0.99, p < 0.001, mean difference 0.4 +/- 2 cm/s). Maximally detectable velocity, however, was strongly dependent on frame rate and insonation angle and reached 42 cm/s under optimal conditions. At higher velocities estimates became random. Direction estimates did depend less on velocity and were accurate in 80-90%. In-plane motion patterns were correctly identified with three ultrasound systems. CONCLUSION: Echo-PIV appears feasible. Velocity estimates are accurate, but the maximal detectable velocity depends strongly on acquisition parameters. Direction estimation works sufficiently, even at higher velocities. Echo-PIV appears to be a promising technical approach to investigate flow patterns by echocardiography. PMID- 22672728 TI - Evaluation of clinical outcomes and bone loss around titanium implants with oxidized surface: six-year follow-up results from a prospective case series study. AB - PURPOSE: The aim of this prospective study was to assess long-term clinical outcomes and peri-implant bone level changes around oxidized implants supporting partial fixed rehabilitations. MATERIALS AND METHODS: Twenty-two partially edentulous patients were included in the study. A total of 33 fixed rehabilitations were placed, supported by 54 titanium implants with oxidized microtextured surface. Prostheses were delivered after 3 and 6 months of implant placement in the mandible and maxilla, respectively. Patients were scheduled for follow-up at 6 and 12 months and then yearly. At each follow-up, plaque level and bleeding scores were assessed and periapical radiographs were taken. The main outcomes were prosthesis success, implant survival, implant success, and marginal bone level change. RESULTS: Three patients were excluded from the study because they did not attend the 1-year follow-up. Nineteen patients, accounting for 49 implants, were followed for at least 6 years after prosthesis delivery. The mean follow-up duration was 81.8 months (range 75-96 months). One mandibular single tooth implant failed after 1 year in a smoker woman. Cumulative implant survival and success at 6 years were 98.0% and 95.9%, respectively. Prosthesis success was 96.7%. The mean peri-implant bone loss at 6 years was 0.76 +/- 0.47 mm. Not significantly (p = .75) greater bone loss was found in the maxilla (0.78 +/- 0.14 mm, n = 19) as compared with the mandible (0.74 +/- 0.59 mm, n = 30). In the maxilla, bone loss was significantly greater around implants supporting partial prostheses as compared with single-tooth implants (p = .03). Full patient satisfaction was reported. CONCLUSION: Implants with oxidized microtextured surface may achieve excellent long-term clinical outcomes in the rehabilitation of partial edentulism. PMID- 22672730 TI - Taking the pressure off in the Emergency Department: evaluation of the prophylactic application of a low shear, soft silicon sacral dressing on high risk medical patients. AB - Pressure injuries are key clinical indicators of care standard. In Australia, pressure injuries increase length of hospital stay by 4.31 and cost $285 million annually. This pilot study examined the effectiveness of sacral dressing in reducing the prevalence of pressure injuries in older, high-risk patients. A non randomised one-sample experimental design was used in this study comprising of four phases. Of the 51 patients recruited to the study, one patient developed a sacral pressure injury compared to six patients identified in a known group with similar demographics who were not approached to participate in the study. The results indicated that patients in the known group were 5.4 times more likely to develop a pressure injury than the intervention group. Findings suggest that applying a protective sacral dressing with a low shear backing as part of a simple standardised prevention injury prevention regime commencing in the Emergency Department was beneficial in the prevention of pressure injury in older 'at high risk' medical patients. PMID- 22672729 TI - Analysis of medical expenditure and socio-economic status in patients with ocular chemical burns in East China: a retrospective study. AB - BACKGROUND: Little has been known regarding the relationship between ocular chemical injury and victims' medical expenditure, income loss and socio-economic status changes. So we conduct this retrospective cross-sectional study in patients with ocular chemical burns in East China. METHODS: Fifty-six patients were enrolled and required to complete a self-report questionnaire consisting of the following contents: entire expenditure on medical treatment; the victims' personal and household per capita income, and income loss caused by the injury; and the changes of socioeconomic status as well. RESULTS: The median expense of medical treatment was CNY 40,000 (approximately US$5,900). The medical expenditure rose significantly with increased injury severity, prolonged hospital stay, and increased frequency of surgery. More than half victims (51.8 %, 29/56) paid all or the majority of medical expense by themselves. The expense of only 5 victims was mainly paid by medical insurance, accounting for less than ten percent (8.9 %, 5/56). The victims' personal and household per capita income both decreased significantly after the injury, with the median reduction being CNY 24,000 and CNY 7,800 (approximately US$3600 and US$1200) per year respectively. The reduction amplitude of personal and household per capita income rose with increased injury severity and prolonged time of care required. The injury caused emotional depression or anxiety in 76.8 % (43/56) victims, and the relationship with their relatives got worse in 51.9 % (29/56) patients. Moreover, only 21.4 % (12/56) patients felt that the whole society gave them care and concern after the injury, whereas 46.4 % (26/56) and 28.6 % (16/56) felt indifference or discrimination from society as a whole (X2 = 16.916, P = 0.028). CONCLUSIONS: The medical expense was a huge economic burden to most victims of ocular chemical burns, and personal and household per capita income of the victims decreased significantly after injury, both of which had a close relationship with the injury severity. Formal legislation was urgently needed to compel the employer to purchase injury or medical insurance and provide more compulsory protection to the population working in high risk occupations. In addition, psychological counseling and instruction shouldn't be neglected in the aid and treatment of victims. PMID- 22672731 TI - Endobronchial ultrasound guided fine needle aspiration versus transcervical mediastinoscopy in nodal staging of non small cell lung cancer: a prospective comparison study. AB - BACKGROUND: At present only few studies directly compare the diagnostic yield of endobronchial ultrasound guided fine needle aspiration (EBUS-FNA) and transcervical video-assisted mediastinoscopy (TM) for mediastinal lymph node staging in patients with NSCLC. If and when EBUS-FNA may replace TM as Gold Standard remains controversial. METHODS: From April 2008 to December 2009, 36 patients with mediastinal lymphadenopathy underwent simultaneous EBUS-FNA/ TM at our institution. Among them were 26 patients with confirmed or suspected NSCLC. RESULTS: A total of 133 samples were obtained by EBUS-FNA and 157 samples by TM. EBUS-FNA achieved significantly less conclusive, but more indeterminate pathological results in comparison to TM (78.7% vs. 98.6%, p < 0.001; 14.9% vs. 1.4%, p = 0.007). Less paratracheal nodes were sampled by EBUS-FNA (right: 46.2% vs. 88.5%, p = 0.003; left: 23.1% vs. 65.4%, p = 0.005), while sampling rates in the subcarinal localisation were comparable (96.2% vs. 80.8%, p = NS). Among patients with confirmed NSCLC and conclusive EBUS-FNA/ TM findings (n = 18), the prevalence of N2/N3 disease was 66.7% (n = 12) according to TM findings. Diverging nodal stages were found in five patients (27.8%). Three patients who were N2 negative in EBUS-FNA were upstaged to N2 or N3 by TM, two patients with N2 status in EBUS-FNA were upstaged to N3 by TM. CONCLUSIONS: Compared to TM, EBUS-FNA had a lower diagnostic yield and resulted in systematic mediastinal nodal understaging. At this point we suggest corroborating negative EBUS-FNA results by transcervical mediastinoscopy. PMID- 22672732 TI - The effects of respiratory training for chronic obstructive pulmonary disease patients: a randomised clinical trial. AB - AIMS AND OBJECTIVES: To assess the effects of respiratory training on lung function, activity tolerance and quality of life in patients with chronic obstructive pulmonary disease. BACKGROUND: For patients with chronic obstructive pulmonary disease, pulmonary rehabilitation can increase activity tolerance and improve their psychological state by relieving dyspnoea and promoting their quality of life. DESIGN: A randomised clinical trial was conducted in a local hospital. METHODS: Patients with chronic obstructive pulmonary disease were randomly assigned to intervention (n=20) and control groups (n=20). Spirometry, six-minute walking distance and quality of life were used to assess the efficacy of respiratory training programme. RESULTS: Significant improvement in lung function, including forced vital capacity (p=0.037), forced expiratory volume in one-second (p=0.006) and per cent predicted forced expiratory volume in one second (p=0.008) in the intervention group. Regarding efficacy of the training programme for patients with chronic obstructive pulmonary disease, in forced expiratory volume in one-second (p=0.024) and per cent predicted forced expiratory volume in one-second (p=0.035), six-minute walking distance significantly increased. In addition, there were significant improvements for symptoms (p=0.018), impact (p<0.001) and total quality of life scores (p<0.001), as well as significantly decreased body mass, airflow obstruction, dyspnoea and exercise capacity index (p=0.004) in the intervention group. CONCLUSIONS: A respiratory training programme for patients with chronic obstructive pulmonary disease was found to relieve dyspnoea, maintain lung function, increase activity tolerance and improve quality of life. RELEVANCE TO CLINICAL PRACTICE: Respiratory training programme can be used as a routine rehabilitation protocol for patients with chronic obstructive pulmonary disease and can be used by nurses as a reference to monitor chronic obstructive pulmonary disease patients' health status. PMID- 22672733 TI - The periodic wetting of leaves enhances water relations and growth of the long lived conifer Araucaria angustifolia. AB - The importance of foliar absorption of water and atmospheric solutes in conifers was recognised in the 1970s, and the importance of fog as a water source in forest environments has been recently demonstrated. Araucaria angustifolia (Araucariaceae) is an emergent tree species that grows in montane forests of southern Brazil, where rainfall and fog are frequent events, leading to frequent wetting of the leaves. Despite anatomical evidence in favour of leaf water absorption, there is no information on the existence and physiological significance of a such process. In this study, we test the hypothesis that the use of atmospheric water by leaves takes place and is physiologically relevant for the species, by comparing growth, water relations and nutritional status between plants grown under two conditions of soil water (well-watered and water stressed plants) and three types of leaf spraying (none, water and nutrient solution spray). Leaf spraying had a greater effect in improving plant water relations when plants were under water stress. Plant growth was more responsive to water available to the leaves than to the roots, and was equally increased by both types of leaf spraying, with no interaction with soil water status. Spraying leaves with nutrient solution increased shoot ramification and raised the concentrations of N, P, K, Zn, Cu and Fe in the roots. Our results provide strong indications that water and nutrients are indeed absorbed by leaves of A. angustifolia, and that this process might be as important as water uptake by its roots. PMID- 22672734 TI - The effect of removable partial dentures on alveolar bone resorption: a retrospective study with cone-beam computed tomography. AB - PURPOSE: The aim of this study was to compare vertical and horizontal mandibular alveolar bone resorption by measuring bone morphological variation in Kennedy Class II removable partial denture (RPD) wearers and non-wearers using cone-beam computed tomography (CBCT). MATERIALS AND METHODS: In total, 124 sites in the CBCT scans of 62 (29 RPD non-wearers, 33 RPD wearers) Kennedy Class II patients were analyzed retrospectively. Three-dimensional representations of the mandible with superimposed cross-sectional slices were developed with the CBCT scans to evaluate the mandibular alveolar height and width by measuring distances between the mandibular canal, mylohyoid ridge, alveolar crest, and lower border of the mandible in four regions (eight sites) of Kennedy Class II non-wearers and wearers of RPDs. RESULTS: Mandibular alveolar bone height and width were significantly lower in edentulous sites when compared with dentate sites in both Kennedy Class II non-wearers and wearers of RPDs (p < 0.05). Additionally, mean vertical and horizontal mandibular bone resorption was significantly higher in RPD wearers than in non-wearers (p < 0.05). CONCLUSIONS: Vertical and horizontal alveolar bone resorption was found to be higher in the RPD wearing patients when comparing the dentate and edentulous sites. PMID- 22672735 TI - Attention and semantic processing during speech: an fMRI study. AB - This fMRI study was conducted to investigate whether language semantics is processed even when attention is not explicitly directed to word meanings. In the "unattended" condition, the subjects performed a visual detection task while hearing semantically related and unrelated word pairs. In the "phoneme" condition, the subjects made phoneme judgements between prime and target words, and in the "word" condition, they indicated whether the words in each word pair were semantically related or unrelated. In the word condition, stronger activity was obtained for unrelated than related words in the superior temporal gyrus/sulcus (STG/STS), lingual/fusiform gyri and cuneus, whereas in the phoneme condition no such effect was observed. However, during the unattended condition, stronger activity was found in the right STG. Our results suggest that both semantic judgement of word pairs and their passive hearing activate the same neural networks but this activation is more restricted in the passive hearing. PMID- 22672736 TI - Large-scale analysis of microRNA evolution. AB - BACKGROUND: In animals, microRNAs (miRNA) are important genetic regulators. Animal miRNAs appear to have expanded in conjunction with an escalation in complexity during early bilaterian evolution. Their small size and high-degree of similarity makes them challenging for phylogenetic approaches. Furthermore, genomic locations encoding miRNAs are not clearly defined in many species. A number of studies have looked at the evolution of individual miRNA families. However, we currently lack resources for large-scale analysis of miRNA evolution. RESULTS: We addressed some of these issues in order to analyse the evolution of miRNAs. We perform syntenic and phylogenetic analysis for miRNAs from 80 animal species. We present synteny maps, phylogenies and functional data for miRNAs across these species. These data represent the basis of our analyses and also act as a resource for the community. CONCLUSIONS: We use these data to explore the distribution of miRNAs across phylogenetic space, characterise their birth and death, and examine functional relationships between miRNAs and other genes. These data confirm a number of previously reported findings on a larger scale and also offer novel insights into the evolution of the miRNA repertoire in animals, and it's genomic organization. PMID- 22672738 TI - Editorial comment to new three-dimensional head-mounted display system, TMDU-S-3D system, for minimally invasive surgery application: procedures for gasless single port radical nephrectomy. PMID- 22672737 TI - Myosins XI-K, XI-1, and XI-2 are required for development of pavement cells, trichomes, and stigmatic papillae in Arabidopsis. AB - BACKGROUND: The positioning and dynamics of vesicles and organelles, and thus the growth of plant cells, is mediated by the acto-myosin system. In Arabidopsis there are 13 class XI myosins which mediate vesicle and organelle transport in different cell types. So far the involvement of five class XI myosins in cell expansion during the shoot and root development has been shown, three of which, XI-1, XI-2, and XI-K, are essential for organelle transport. RESULTS: Simultaneous depletion of Arabidopsis class XI myosins XI-K, XI-1, and XI-2 in double and triple mutant plants affected the growth of several types of epidermal cells. The size and shape of trichomes, leaf pavement cells and the elongation of the stigmatic papillae of double and triple mutant plants were affected to different extent. Reduced cell size led to significant size reduction of shoot organs in the case of triple mutant, affecting bolt formation, flowering time and fertility. Phenotype analysis revealed that the reduced fertility of triple mutant plants was caused by delayed or insufficient development of pistils. CONCLUSIONS: We conclude that the class XI myosins XI-K, XI-1 and XI-2 have partially redundant roles in the growth of shoot epidermis. Myosin XI-K plays more important role whereas myosins XI-1 and XI-2 have minor roles in the determination of size and shape of epidermal cells, because the absence of these two myosins is compensated by XI-K. Co-operation between myosins XI-K and XI-2 appears to play an important role in these processes. PMID- 22672739 TI - How many steps are enough to avoid severe physical inactivity in patients with chronic obstructive pulmonary disease? AB - While prognostically valuable, physical activity monitoring is not routinely performed for patients with COPD. We aimed to determine the number of daily steps associated with severe physical inactivity (physical activity level <1.40) in this population. We found that a daily step value <4580 is associated with severe physical inactivity. Our results are of significant value for clinicians counselling patients with COPD to help avoid the morbidity of severe physical inactivity. PMID- 22672740 TI - Spatiotemporal coordination behaviors in futsal (indoor football) are guided by informational game constraints. AB - This report investigated the behavioral dynamics of teams in futsal game practice when the goalkeeper of the attacking team is substituted for an extra outfield player. To this end, the lateral and longitudinal displacements of the ball and both teams, as well as their kinematics expressed in angles and radial distances from the goal center, were obtained and subjected to relative phase analysis. The results demonstrated (a) stronger phase relations with the ball for the defending team than the attacking team for both coordinate systems, (b) phase relations between each team and ball, and, to a lesser extent, between teams themselves, produced greater stabilities in the lateral (side-to-side) direction than the longitudinal (forward-backward) direction, and (c) phase attractions were most pronounced for the defending team and ball when using angles as a measure of association, indicating ball position and goal location as key informational constraints for futsal game behavior. These findings advance understanding of self-organizing sports game dynamics with implications for sports practice. PMID- 22672741 TI - TLR4 and TLR9 are induced in oral lichen planus. AB - BACKGROUND: The role of Toll-like receptors (TLRs) has been elucidated in many human infectious, autoimmune and neoplastic diseases. Previously, TLR2 and TLR4 expression in oral lichen planus (OLP) was described. The aim of our study was to examine expression patterns of TLR4 and TLR9 in normal oral mucosa and OLP and describe the effect of topical tacrolimus treatment on the expression of TLR4 and TLR9 in OLP. METHODS: Toll-like receptor 4 and TLR9 expression was analysed by immunohistochemistry in five samples of normal oral mucosa and 50 samples of OLP (31 representing clinically white and 19 clinically erythematous/erosive lesions). We evaluated also the effect of topical tacrolimus on TLR4 and TLR9 expression in a patient with OLP. RESULTS: Toll-like receptor 4 and TLR9 expression was increased in OLP epithelium compared with normal epithelium (P < 0.001); no significant difference between the two clinical types of OLP was observed. TLR9 expression was strongest in the superficial layer of the epithelium (P < 0.001), while the expression of TLR4 was strongest in the basal layer (P < 0.001). Treatment of OLP lesions with topical tacrolimus resulted in clinical improvement but had no effect on TLR expression levels. CONCLUSIONS: Toll-like receptor 4 and TLR9 are induced in OLP; our finding confirms the results of a previous study. TLR4 and TLR9 may play a part in the pathogenesis of OLP. Further studies are needed to dissect the definitive role of TLRs in OLP pathogenesis and progression and to determine the effect of tacrolimus on the function of TLRs. PMID- 22672742 TI - Vitamin D deficiency in patients with myasthenia gravis and improvement of fatigue after supplementation of vitamin D3: a pilot study. AB - BACKGROUND: Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disorder. Vitamin D has important roles both in the autoimmune response and in skeletal muscles. We determined the levels of 25-hydroxy vitamin D [25(OH)D] in patients with MG and in healthy subjects to determine whether vitamin D deficiency is present in MG and whether vitamin D supplementation has beneficial effects on fatigue. METHODS: Plasma levels of 25(OH)D were analyzed in 33 patients with MG (22 males; mean age, 58 years) and in 50 healthy age- and sex matched blood donors, without vitamin D3 medication. MG composite (MGC) score assessed fatigue. Thirteen patients with MG without previous vitamin D3 supplementation were started on vitamin D3 supplementation (cholecalciferol) 800 IU/day, with a follow-up examination after 2.5-10 months (mean, 6 months). RESULTS: Patients with MG without pre-existing vitamin D3 supplementation (N = 16) had a mean MGC of 4.5 and lower plasma 25(OH)D levels (mean, 51 +/- 19 nM) than healthy controls (69 +/- 21 nM) (P = 0.017). Seventeen patients had pre existing vitamin D3 supplementation, because of corticosteroid treatment, and their mean 25(OH)D was 79 +/- 22 nM and mean MGC was 5.5. In the 13 patients who received cholecalciferol, 25(OH)D was overall increased at follow-up with 22% (P = 0.033) and MGC score improved by 38% (P = 0.05). CONCLUSIONS: Plasma 25(OH)D levels are significantly lower in patients with MG compared with healthy controls. As vitamin D has beneficial effects on the autoimmune response and on fatigue score in patients with MG, we suggest monitoring this parameter in patients with MG and supplementation with vitamin D3 when 25(OH)D levels are low. PMID- 22672743 TI - Bioactive oligopeptides in dermatology: Part I. AB - Short sequence amino acids or oligopeptides represent a relatively new and promising area of dermatology. Oligopeptides are defined as peptide sequences ranging from 2 to 20 amino acids. This class of proteins includes potent biologically active compounds, which can modulate various cellular and molecular processes. The medical potential of short sequence peptides was initially characterized many decades ago with the identification of biological mediators such as angiotensin, vasopressin, oxytocin and bradykinin. However, the role of oligopeptides in affecting biological activity within the skin has only recently been explored. Currently, the dermatologic use of protein peptide fragments is a rapidly growing field of research. Recent studies suggest that treatment with various biologically active peptides can result in favourable clinical outcomes such as for the treatment of hyperpigmentation disorders with tyrosinase inhibitors and the use of collagen synthesis modulators to diminish skin laxity. In this review, we explore the roles of biologically active short sequence peptides as potential therapeutics through the modulation of collagen, elastin and melanin synthesis. PMID- 22672744 TI - Extent of nucleus pulposus migration in the annulus of porcine intervertebral discs exposed to cyclic flexion only versus cyclic flexion and extension. AB - BACKGROUND: Repeated flexion of an intervertebral disc has been identified as a mechanism to produce posterior herniations. Repeated extension under certain conditions has also been shown to cause the nucleus of partially herniated discs to reverse and migrate anteriorly. While research shows that the nucleus pulposus migrates anteriorly in extension and infiltrates the annulus posteriorly in flexion, it is not known if a cycle of flexion followed by a cycle of extension produces more or less annular damage compared to pure flexion alone. METHODS: Two groups of porcine spinal motion segments were exposed to either repeated flexion with extension or just repeated flexion. Digitized photographs of dissected specimens enhanced with a radio-opaque blue dye enabled the quantification of the area of annulus infiltrated with nucleus pulposus. FINDINGS: Specimens exposed to both flexion and extension showed significantly more annular damage and axial creep compared to those exposed to flexion alone. INTERPRETATION: It would appear that while flexion alone can still cause nucleus pulposus to track through the annulus of an intervertebral disc, the effects are compounded when it is followed by a subsequent cycle of extension. Thus, movements which require both repetitive flexion and extension, have the potential to produce more annular damage than those which require merely flexion. PMID- 22672745 TI - Formation of silicon nanostructures with a combination of spacer technology and deep reactive ion etching. AB - A new method of fabricating high aspect ratio nanostructures in silicon without the use of sub-micron lithographic technique is reported. The proposed method comprises two important steps including the use of CMOS spacer technique to form silicon nitride nanostructure masking followed by deep reactive ion etching (DRIE) of the silicon substrate to form the final silicon nanostructures. Silicon dioxide is used as the sacrificial layer to form the silicon nitride nanostructures. With DRIE a high etch selectivity of 50:1 between silicon and silicon nitride was achieved. The use of the spacer technique is particularly advantageous where self-aligned nanostructures with potentially unlimited lengths are formed without the need of submicron lithographic tools and resist materials. With this method, uniform arrays of 100 nm silicon nanostructures which are at least 4 MUm tall with aspect ratio higher than 40 were successfully fabricated. PMID- 22672746 TI - Racial and geographic variation in coronary heart disease mortality trends. AB - BACKGROUND: Magnitudes, geographic and racial variation in trends in coronary heart disease (CHD) mortality within the US require updating for health services and health disparities research. Therefore the aim of this study is to present data on these trends through 2007. METHODS: Data for CHD were analyzed using the US mortality files for 1999-2007 obtained from the US Centers for Disease Control and Prevention. Age-adjusted annual death rates were computed for non-Hispanic African Americans (AA) and European Americans (EA) aged 35-84 years. The direct method was used to standardize rates by age, using the 2000 US standard population. Joinpoint regression models were used to evaluate trends, expressed as annual percent change (APC). RESULTS: For both AA men and women the magnitude in CHD mortality is higher compared to EA men and women, respectively. Between 1999 and 2007 the rate declined both in AA and in EA of both sexes in every geographic division; however, relative declines varied. For example, among men, relative average annual declines ranged from 3.2% to 4.7% in AA and from 4.4% to 5.5% in EA among geographic divisions. In women, rates declined more in later years of the decade and in women over 54 years. In 2007, age-adjusted death rate per 100,000 for CHD ranged from 93 in EA women in New England to 345 in AA men in the East North Central division. In EA, areas near the Ohio and lower Mississippi Rivers had above average rates. Disparities in trends by urbanization level were also found. For AA in the East North Central division, the APC was similar in large central metro (-4.2), large fringe metro (-4.3), medium metro urbanization strata (-4.4), and small metro (-3.9). APC was somewhat higher in the micropolitan/non-metro (-5.3), and especially the non-core/non-metro (-6.5). For EA in the East South Central division, the APC was higher in large central metro (-5.3), large fringe metro (-4.3) and medium metro urbanization strata (-5.1) than in small metro (-3.8), micropolitan/non-metro (-4.0), and non-core/non-metro (-3.3) urbanization strata. CONCLUSIONS: Between 1999 and 2007, the level and rate of decline in CHD mortality displayed persistent disparities. Declines were greater in EA than AA racial groups. Rates were greater in the Ohio and Mississippi River than other geographic regions. PMID- 22672747 TI - Feasibility of MR imaging/MR spectroscopy-planned focal partial salvage permanent prostate implant (PPI) for localized recurrence after initial PPI for prostate cancer. AB - PURPOSE: To assess the feasibility of magnetic resonance imaging (MRI)-planned partial salvage permanent prostate implant (psPPI) among patients with biopsy proven local recurrence after initial PPI without evidence of distant disease. METHODS AND MATERIALS: From 2003-2009, 15 patients underwent MRI/magnetic resonance spectroscopy (MRS) planning for salvage brachytherapy (psPPI, I-125 [n=14; 144 Gy]; Pd-103 [n=1; 125 Gy]) without hormone therapy. Full dose was prescribed to areas of recurrence and underdosage, without entire prostate implantation. Limiting urethral and rectal toxicity was prioritized. Follow-up was from salvage date to prostate-specific antigen (PSA) concentration failure (Phoenix criteria = nadir + 2.0; ASTRO = 3 consecutive rises), recurrence, distant metastases, or last follow-up PSA level. Progression-free survival (PFS) was defined as no PSA failure or biopsy-proven recurrence without all-cause mortality. Toxicity was scored using Common Terminology Criteria for Adverse Events version 4.0. RESULTS: At salvage, median age was 68 years, and PSA concentration was 3.5 ng/mL (range, 0.9-5.6 ng/mL). Abnormal MRI/MRS findings were evident in 40% of patients. Biopsy-proven recurrences consisted of a single focus (80%) or 2 foci (20%). At recurrence, Gleason score was 6 (67%) or >=7 (27%). Median interval between initial and salvage implantation was 69 months (range, 28-132 months). psPPI planning characteristics limited doses to the rectum (mean V100 = 0.5% [0.07 cc]) and urethra (V100 = 12% [0.3 cc]). At median follow-up (23.3 months; range, 8-88 months), treatment failure (n=2) resulted only in localized recurrence; both patients underwent second psPPI with follow-up PSA tests at 12 and 26 months, resulting in 0.6 and 0.7 ng/mL, respectively. American Society for Radiation Oncology PFS rates at 1, 2, and 3 years were 86.7%, 78.4%, and 62.7%, respectively, with 5 patients for whom treatment failed (n=3 with negative transrectal ultrasound-guided biopsy results). Phoenix PFS rates at 1, 2, and 3 years were 100%, 100%, and 71.4%. 73%, respectively; achieved PSA nadir of <0.5 ng/mL; and 47% of patients had a nadir of <0.1 ng/mL. Treatment-related toxicity was minimal, with no operative interventions, fistulas, or other grade >=3 gastrointestinal (GI)/genitourinary (GU) toxicity. Thirteen percent had grade 1 GI and 33% had grade 2 GU toxicities. Postsalvage, 20% of patients had no erectile dysfunction, 67% of patients had medication responsive erectile dysfunction, and 13% of patients had erectile dysfunction refractory to medication. CONCLUSIONS: Focal psPPI with MR-planning in highly selected patients is feasible with short-term control comparable to conventional salvage, with less toxicity. Longer follow-up is needed to confirm its impact on quality of life and treatment. PMID- 22672748 TI - Mitigation and treatment of radiation-induced thoracic injury with a cyclooxygenase-2 inhibitor, celecoxib. AB - PURPOSE: To test whether a cyclooxygenase-2 inhibitor (celecoxib) could reduce mortality resulting from radiation-induced pneumonitis. METHODS AND MATERIALS: Celecoxib was given to mice twice daily for 40 consecutive days starting on the day of local thoracic irradiation (LTI) or 40 or 80 days later. C3Hf/KamLaw mice were observed for morbidity, and time to death was determined. Results were analyzed using the Cox proportional hazards model. RESULTS: Timing of celecoxib relative to LTI determined efficacy. A significant reduction in time to death was achieved only when celecoxib was started 80 days after LTI, corresponding to the time when pneumonitis is expressed. For these mice the reduction in mortality was quantified as a hazard ratio for mortality of treated vs untreated of 0.36 (95% confidence interval [CI] 0.24-0.53), thus significantly less than 1.0. Correspondingly, the median lethal dose for treated mice (12.9 Gy; 95% CI 12.55 13.25 Gy) was significantly (P=.026) higher than for untreated mice (12.4 Gy; 95% CI 12.2-12.65 Gy). CONCLUSIONS: Celecoxib significantly reduced lung toxicity when administered months after LTI when the deleterious effects of radiation were expressed. The schedule-dependent reduction in fatal pneumonitis suggests that celecoxib could be clinically useful by reintroduction of treatment months after completion of radiation therapy. These findings may be important for designing clinical trials using cyclooxygenase-2 inhibitors to treat radiation-induced lung toxicity as a complement to concurrent radiation therapy of lung cancers. PMID- 22672749 TI - KRAS mutation status and clinical outcome of preoperative chemoradiation with cetuximab in locally advanced rectal cancer: a pooled analysis of 2 phase II trials. AB - PURPOSE: Cetuximab-containing chemotherapy is known to be effective for KRAS wild type metastatic colorectal cancer; however, it is not clear whether cetuximab based preoperative chemoradiation confers an additional benefit compared with chemoradiation without cetuximab in patients with locally advanced rectal cancer. METHODS AND MATERIALS: We analyzed EGFR, KRAS, BRAF, and PIK3CA mutation status with direct sequencing and epidermal growth factor receptor (EGFR) and Phosphatase and tensin homolog (PTEN) expression status with immunohistochemistry in tumor samples of 82 patients with locally advanced rectal cancer who were enrolled in the IRIX trial (preoperative chemoradiation with irinotecan and capecitabine; n=44) or the ERBIRIX trial (preoperative chemoradiation with irinotecan and capecitabine plus cetuximab; n=38). Both trials were similarly designed except for the administration of cetuximab; radiation therapy was administered at a dose of 50.4 Gy/28 fractions and irinotecan and capecitabine were given at doses of 40 mg/m2 weekly and 1650 mg/m2/day, respectively, for 5 days per week. In the ERBIRIX trial, cetuximab was additionally given with a loading dose of 400 mg/m2 on 1 week before radiation, and 250 mg/m2 weekly thereafter. RESULTS: Baseline characteristics before chemoradiation were similar between the 2 trial cohorts. A KRAS mutation in codon 12, 13, and 61 was noted in 15 (34%) patients in the IRIX cohort and 5 (13%) in the ERBIRIX cohort (P=.028). Among 62 KRAS wild-type cancer patients, major pathologic response rate, disease free survival and pathologic stage did not differ significantly between the 2 cohorts. No mutations were detected in BRAF exon 11 and 15, PIK3CA exon 9 and 20, or EGFR exon 18-24 in any of the 82 patients, and PTEN and EGFR expression were not predictive of clinical outcome. CONCLUSIONS: In patients with KRAS wild-type locally advanced rectal cancer, the addition of cetuximab to the chemoradiation with irinotecan plus capecitabine regimen was not associated with improved clinical outcome compared with chemoradiation without cetuximab. PMID- 22672750 TI - Flattening filter free vs flattened beams for breast irradiation. AB - PURPOSE: Flattening filter free (FFF) beams offer the potential for a higher dose rate, shorter treatment time, and lower peripheral dose. To investigate their role in large-field treatments, this study compared flattened and FFF beams for breast irradiation. METHODS AND MATERIALS: Ten left breast clinical plans comprising 2 tangential beams and a medially located 3-field simultaneous integrated boost (SIB) were replanned. Full intensity modulated radiotherapy (IMRT), hybrid IMRT, electronic tissue compensator (ETC), and multiple static field treatment plans were created for the elective breast volume using flattened and FFF beams, in combination with a 3-field IMRT SIB. Plan quality was assessed and delivery times were measured for all plans for 1 patient. Out-of-field doses were measured using an ionization chamber for an IMRT plan optimized on a corner of simple cubic phantom for both flattened and FFF beams. RESULTS: For each technique, mean target volume metrics (planning target volume coverage, homogeneity, conformity) were typically within 3% for flattened and FFF beams. Larger mean differences in boost conformity favoring flattened hybrid (7.2%) and full IMRT (5.5%) plans may have reflected limitations in plan normalization. Calculated heart and ipsilateral lung doses were comparable; however, both flattened and FFF low-dose phantom measurements were substantially higher than calculated values, rendering the comparison of low dose in the contralateral breast uncertain. Beam delivery times were on average 31% less for FFF. CONCLUSIONS: In general, target volume metrics for flattened and FFF plans were comparable. The planning system did not seem to allow for accurate peripheral dose evaluation. FFF was associated with a potentially shorter treatment time. All 4 IMRT techniques allowed FFF beams to generate acceptable plans for breast IMRT. PMID- 22672751 TI - A prospective cohort study to compare treatment results between 2 fractionation schedules of high-dose-rate intracavitary brachytherapy (HDR-ICBT) in patients with cervical cancer. AB - PURPOSE: To compare the treatment results of 2 fractionation schedules for high dose-rate intracavitary brachytherapy (HDR-ICBT) in patients with cervical cancer. METHODS AND MATERIALS: From June 2001 through January 2008, 267 patients with stage IB-IVA cervical cancer were enrolled in the study. All patients underwent 4-field pelvic irradiation and HDR-ICBT. The median central and parametrial doses were 39.6 Gy and 45 Gy, respectively. Patient underwent either 6 Gy*4 (HDR-4) (n=144) or 4.5 Gy*6 (HDR-6) (n=123) to point A of ICBT using 192Ir isotope twice weekly. The rates of overall survival, locoregional failure, distant metastasis, proctitis, cystitis, and enterocolitis were compared between HDR-4 and HDR-6. RESULTS: There were no significant differences in the demographic data between HDR-4 and HDR-6 except for total treatment time. The 5 year proctitis rates were 23.0% and 21.5% in HDR-4 and HDR-6 (P=.399), respectively. The corresponding rates of grade 2-4 proctitis were 18.7% and 9.6% (P=.060). The corresponding rates of grades 3-4 proctitis were 5.2% and 1.3% (P=.231). Subgroup analysis revealed that HDR-4 significantly increased grade 2-4 proctitis in patients aged>=62 years old (P=.012) but not in patients aged<62 years (P=.976). The rates of overall survival, locoregional failure, distant metastasis, cystitis, and enterocolitis were not significantly different between HDR-4 and HDR-6 schedules. CONCLUSION: The small fraction size of HDR-ICBT is associated with grade 2 proctitis without compromise of prognosis in elderly patients. This schedule is suggested for patients who tolerate an additional 2 applications of HDR-ICBT. PMID- 22672752 TI - Multi-institutional experience of ductal carcinoma in situ in black vs white patients treated with breast-conserving surgery and whole breast radiation therapy. AB - PURPOSE: Given the paucity of data on racial disparities in ductal carcinoma in situ (DCIS), the data from a multi-institutional cohort of DCIS patients treated with breast-conserving surgery and whole breast radiation therapy (RT) were analyzed to determine whether racial disparities or differences exist. METHODS AND MATERIALS: A total of 533 white and 76 black DCIS patients from 3 university based cancer centers were uniformly treated with breast-conserving surgery and RT. All patient data were collected and analyzed as a function of race. RESULTS: The median follow-up was 5.2 years. No significant racial differences were seen in tumor size, age at diagnosis, estrogen receptor status, necrosis, or grade (all P>.05). Of the treatment parameters, the RT dose delivered, boost, positive margin rates, frequency of hormone receptor status assessment, and receipt of hormonal therapy for the 2 cohorts did not significantly differ (all P>.05). The local relapse-free survival was similar at 5 years (96.1% and 98.1%, P=.399) and 10 years (92.8% vs 95.8%, P=.360), with no significant overall survival difference at 10 years (94.0% vs 88.9%, P=.290) between the white and black patients, respectively. On multivariate analysis, race was not an independent predictor of local relapse-free survival or overall survival when accounting for age, grade, and margin status. CONCLUSION: In our large cohort of DCIS patients uniformly treated at 3 institutions with breast conservation without any apparent differences in treatment delivery parameters, we demonstrated that the clinical and pathologic features and local survival outcomes did not differ as a function of race. Our results suggest that when black patients with DCIS are appropriately selected for breast conservation and receive adjuvant RT without racial disparities in the treatment parameters, differences in the outcomes as a function of race do not exist. PMID- 22672753 TI - Automatic segmentation and online virtualCT in head-and-neck adaptive radiation therapy. AB - PURPOSE: The purpose of this work was to develop and validate an efficient and automatic strategy to generate online virtual computed tomography (CT) scans for adaptive radiation therapy (ART) in head-and-neck (HN) cancer treatment. METHOD: We retrospectively analyzed 20 patients, treated with intensity modulated radiation therapy (IMRT), for an HN malignancy. Different anatomical structures were considered: mandible, parotid glands, and nodal gross tumor volume (nGTV). We generated 28 virtualCT scans by means of nonrigid registration of simulation computed tomography (CTsim) and cone beam CT images (CBCTs), acquired for patient setup. We validated our approach by considering the real replanning CT (CTrepl) as ground truth. We computed the Dice coefficient (DSC), center of mass (COM) distance, and root mean square error (RMSE) between correspondent points located on the automatically segmented structures on CBCT and virtualCT. RESULTS: Residual deformation between CTrepl and CBCT was below one voxel. Median DSC was around 0.8 for mandible and parotid glands, but only 0.55 for nGTV, because of the fairly homogeneous surrounding soft tissues and of its small volume. Median COM distance and RMSE were comparable with image resolution. No significant correlation between RMSE and initial or final deformation was found. CONCLUSION: The analysis provides evidence that deformable image registration may contribute significantly in reducing the need of full CT-based replanning in HN radiation therapy by supporting swift and objective decision-making in clinical practice. Further work is needed to strengthen algorithm potential in nGTV localization. PMID- 22672754 TI - 5-Androstene-3beta,17beta-diol promotes recovery of immature hematopoietic cells following myelosuppressive radiation and synergizes with thrombopoietin. AB - PURPOSE: 5-Androstene-3beta,17beta-diol (5-AED) stimulates recovery of hematopoiesis after exposure to radiation. To elucidate its cellular targets, the effects of 5-AED alone and in combination with (pegylated) granulocyte colony stimulating factor and thrombopoietin (TPO) on immature hematopoietic progenitor cells were evaluated following total body irradiation. METHODS AND MATERIALS: BALB/c mice were exposed to radiation delivered as a single or as a fractionated dose, and recovery of bone marrow progenitors and peripheral blood parameters was assessed. RESULTS: BALB/c mice treated with 5-AED displayed accelerated multilineage blood cell recovery and elevated bone marrow (BM) cellularity and numbers of progenitor cells. The spleen colony-forming unit (CFU-S) assay, representing the life-saving short-term repopulating cells in BM of irradiated donor mice revealed that combined treatment with 5-AED plus TPO resulted in a 20.1-fold increase in CFU-S relative to that of placebo controls, and a 3.7 and 3.1-fold increase in comparison to 5-AED and TPO, whereas no effect was seen of Peg-G-CSF with or without 5-AED. Contrary to TPO, 5-AED also stimulated reconstitution of the more immature marrow repopulating (MRA) cells. CONCLUSIONS: 5-AED potently counteracts the hematopoietic effects of radiation-induced myelosuppression and promotes multilineage reconstitution by stimulating immature bone marrow cells in a pattern distinct from, but synergistic with TPO. PMID- 22672755 TI - Role of salvage radiation therapy for patients with relapsed or refractory hodgkin lymphoma who failed autologous stem cell transplant. AB - PURPOSE: To analyze, through chart review, the efficacy of salvage radiation therapy (sRT) for relapsed or progressive Hodgkin lymphoma (HL) patients who failed autologous stem cell transplant (ASCT). PATIENTS AND METHODS: Among 347 patients with recurrent/refractory HL who received ASCT from 1986-2006, 163 had post-ASCT progression or relapse. Of these, 56 received sRT and form the basis of this report. Median age at sRT was 30 years (range, 17-59 years). Disease was confined to lymph nodes in 27 patients, whereas 24 had both nodal and extranodal disease. Salvage radiation therapy alone was given in 34 patients (61%), and sRT plus chemotherapy was given in 22 (39%). Median interval from ASCT to sRT was 0.8 years (range, 0.1-5.6 years). The median dose was 35 Gy (range, 8-40.3 Gy). The sRT technique was extended-field in 14 patients (25%) and involved-field in 42 (75%). RESULTS: The median follow-up from sRT was 31.3 months (range, 0.2-205.5 months). Overall response rate was 84% (complete response: 36%; partial response: 48%). The median overall survival was 40.8 months (95% confidence interval, 34.2 56.3 months). The 5-year overall survival was 29% (95% confidence interval, 14% 44%). The 2-year progression-free survival (PFS) was 16%; the 2-year local PFS was 65%, whereas the 2-year systemic PFS was 17%. The 1-year PFS was higher in patients in whom all diseased sites were irradiated (49%) compared with those in whom only the symptomatic site was treated (22%, P=.07). Among 20 alive patients, 5 were disease free (at 6.4, 6.8, 7.4, 7.9, and 17.1 years). CONCLUSION: For patients with HL who fail ASCT, a selective use of RT provides a durable local control rate of 65% at 2 years and should be considered as part of the standard management plan for the palliation of incurable HL. Occasionally irradiation of truly localized disease can lead to long-term survival. PMID- 22672756 TI - Thyroid adenomas after solid cancer in childhood. AB - PURPOSE: Very few childhood cancer survivor studies have been devoted to thyroid adenomas. We assessed the role of chemotherapy and the radiation dose to the thyroid in the risk of thyroid adenoma after childhood cancer. METHODS AND MATERIALS: A cohort of 3254 2-year survivors of a solid childhood cancer treated in 5 French centers before 1986 was established. The dose received by the isthmus and the 2 lobes of the thyroid gland during each course of radiation therapy was estimated after reconstruction of the actual radiation therapy conditions in which each child was treated as well as the dose received at other anatomical sites of interest. RESULTS: After a median follow-up of 25 years, 71 patients had developed a thyroid adenoma. The risk strongly increased with the radiation dose to the thyroid up to a few Gray, plateaued, and declined for high doses. Chemotherapy slightly increased the risk when administered alone but also lowered the slope of the dose-response curve for the radiation dose to the thyroid. Overall, for doses up to a few Gray, the excess relative risk of thyroid adenoma per Gray was 2.8 (90% CI: 1.2-6.9), but it was 5.5 (90% CI: 1.9-25.9) in patients who had not received chemotherapy or who had received only 1 drug, and 1.1 (90% CI: 0.4-3.4) in the children who had received more than 1 drug (P=.06, for the difference). The excess relative risk per Gray was also higher for younger children at the time of radiation therapy than for their older counterparts and was higher before attaining 40 years of age than subsequently. CONCLUSIONS: The overall pattern of thyroid adenoma after radiation therapy for a childhood cancer appears to be similar to that observed for thyroid carcinoma. PMID- 22672757 TI - Sacral pressure ulcer successfully treated with traction, resulting in a reduction of wound deformity. PMID- 22672758 TI - Molecular genetics of the adrenocortical axis and breeding for robustness. AB - The concept of robustness refers to the combination of a high production potential and a low sensitivity to environmental perturbations. The importance of robustness-related traits in breeding objectives is progressively increasing toward the production of animals with a high production level in a wide range of climatic conditions and production systems, together with a high level of animal welfare. Current strategies to increase robustness include selection for "functional traits," such as skeletal and cardiovascular integrity, disease resistance, and mortality at various stages. It is also possible to use global evaluation of sensitivity to the environment (eg reaction norm analysis or canalization), but these techniques are difficult to implement in practice. The glucocorticoid hormones released by the adrenal cortex exert a wide range of effects on metabolism, the cardiovascular system, inflammatory processes, and brain function, for example. Protein catabolism toward energy production and storage (lipids and glycogen) supports their pivotal role in stress responses aiming at the adaptation and survival of individuals under strong environmental pressure. Large individual variations have been described in adrenocortical axis activity, with important physiopathological consequences. In terms of animal production, higher cortisol levels have negative effects on growth rate and feed efficiency and increase the fat:lean ratio of carcasses. On the contrary, cortisol has positive effects on functional traits and adaptation. Intense selection for lean tissue growth and more generally high protein output during the past decades has concomitantly reduced cortisol production, which may be responsible for the negative effects of selection on functional traits. In this paper, we review experimental evidence suggesting that the balance between production and functional traits was modified in favor of improved robustness by selecting animals with higher adrenocortical axis activity, as well as the molecular genetic tools that can be used to fine-tune this objective. PMID- 22672759 TI - Potential plasma biomarkers for progression of knee osteoarthritis using glycoproteomic analysis coupled with a 2D-LC-MALDI system. AB - BACKGROUND: Although osteoarthritis (OA) is a highly prevalent joint disease, to date, no reliable biomarkers have been found for the disease. In this study, we attempted to identify factors the amounts of which significantly change in association with the progression of knee OA. METHODS: A total of 68 subjects with primary knee OA were enrolled in the study. These subjects were followed up over an 18-month period, and plasma and serum samples were obtained together with knee radiographs every 6 months, i.e., 0, 6, 12 and 18 months after the enrollment. Progressors and non-progressors were determined from the changes on radiographs, and plasma samples from those subjects were subjected to N-glycoproteomic 2D-LC MALDI analysis. MS peaks were identified, and intensities for respective peaks were compared between the progressors and non-progressors to find the peak intensities of which differed significantly between the two groups of subjects. Proteins represented by the chosen peaks were identified by MS/MS analysis. Expression of the identified proteins was evaluated in synovial tissues from 10 OA knee joints by in situ hybridization, western blotting analysis and ELISA. RESULTS: Among the subjects involved in the study, 3 subjects were determined to be progressors, and 6 plasma and serum samples from these subjects were subjected to the analysis together with another 6 samples from the non-progressors. More than 3000 MS peaks were identified by N-glycoproteomic 2D-LC-MALDI analysis. Among them, 4 peaks were found to have significantly different peak intensities between the progressors and non-progressors. MS/MS analysis revealed that these peaks represented clusterin, hemopexin, alpha-1 acid glycoprotein-2, and macrophage stimulating protein, respectively. The expression of these genes in OA synovium was confirmed by in situ hybridization, and for clusterin and hemopexin, by western blotting analysis and ELISA as well. CONCLUSIONS: In this study, 4 potential biomarkers were identified as potential prognostic markers for knee OA through N-glycoproteomic analysis. To the best of our knowledge, this is the first report for the use of glycoproteomic technology in exploring potential biomarkers for knee OA. PMID- 22672760 TI - Ligand- and structure-based drug design strategies and PPARdelta/alpha selectivity. AB - Peroxisome-proliferator-activated receptors are a class of nuclear receptors with three subtypes: alpha, gamma and delta. Their main function is regulating gene transcription related to lipid and carbohydrate metabolism. Currently, there are no peroxisome-proliferator-activated receptors delta drugs being marketed. In this work, we studied a data set of 70 compounds with alpha and delta activity. Three partial least square models were created, and molecular docking studies were performed to understand the main reasons for peroxisome-proliferator activated receptors delta selectivity. The obtained results showed that some molecular descriptors (log P, hydration energy, steric and polar properties) are related to the main interactions that can direct ligands to a particular peroxisome-proliferator-activated receptors subtype. PMID- 22672761 TI - Isolation and characterisation of an antifolate insensitive (afi1) mutant of Arabidopsis thaliana. AB - Antifolates can impair the synthesis and/or function of folates in living organisms. Mechanisms of resistance or tolerance to antifolates have been mainly described in plants using the drug methotrexate. In this work, the antifolate trimethoprim (TMP) was used with the aim of revealing a novel mechanism of resistance. EMS mutagenised seeds from Arabidopsis were screened to isolate individuals insensitive to TMP. Genetic analysis revealed a homozygous recessive mutation that segregates with the phenotype of tolerance to 50 MUm TMP. Mapping analysis localised the mutation at the end of the short arm of chromosome 3. Preliminary characterisation demonstrated up-regulation of several genes from the folate biosynthetic pathway in the TMP insensitive mutant, and a slight increase in total folate content in the mutant as compared with the Col-0 control. Moreover, sequence analysis of the DHFR (dihydrofolate reductase) genes, which encode a known target for resistance to antifolates, did not reveal any changes. This study is the first report of a stable mutant insensitive (afi1) to the antifolate trimethoprim in plants, and suggests the existence of a novel mechanism of resistance to antifolates. PMID- 22672762 TI - Electrochemical detection of the binding of Bacillus anthracis protective antigen (PA) to the membrane receptor on macrophages through release of nitric oxide. AB - Anthrax is a serious bacterial disease of man and animals whose pathogenesis involves the secretion of lethal toxins in the host. The intracellular delivery of toxic complexes involves a complex structural rearrangement of sub-domains of the exotoxin protective antigen (PA). We have used a biocompatible microelectrode array, coated with J774 mouse macrophages, to detect PA binding and intracellular signaling resulting in nitric oxide (NO) release. We have found that exposure of macrophages to PA in vitro activates the inducible isoform of NO synthase (iNOS), thus increasing the extracellular concentration of NO and nitrite, in a dose- and time-dependent manner. However, the cell-binding domain 4 of PA (PA4) could substitute for full-length PA to achieve equivalent NO release, suggesting that the heptamerisation of PA, ultimately required to deliver toxic complexes into the cell, is not a requirement for the activation of an intracellular cascade through the ERK 1/2 and the PI-3K/ Akt kinase pathways and that these events could be triggered by the binding of PA4 alone to its cell membrane receptor. Further, we have found that pre-incubation of the cells with azidothymidine, a pro-oxidant drug, significantly improves the limit of detection of rPA-induced NO release thus offering a sensitive tool for the analysis of the kinetics of anthrax intoxication and ultimately drug discovery. PMID- 22672763 TI - Efficient one-pot synthesis of molecularly imprinted silica nanospheres embedded carbon dots for fluorescent dopamine optosensing. AB - A new type of eco-friendly molecularly imprinted polymer (MIP) was synthesized through an efficient one-pot room-temperature sol-gel polymerization and applied as a molecular recognition element to construct dopamine (DA) fluorescence (FL) optosensor. Highly luminescent carbon dots (CDs) were firstly synthesized via a one-step reaction in organosilane, and their surface were anchored with MIP matrix (CDs@MIP). The resulting composite of a synergetic combination of CDs with MIP showed high photostability and template selectivity. Moreover, the composite allowed a highly sensitive determination of DA via FL intensity decreasing when removal of the original templates. The new MIP-based DA sensing protocol was applied to detect DA concentration in aqueous solution, the relative FL intensity of CDs@MIP decreased linearly with the increasing DA in the concentration range of 25-500nM with a detection limit (3sigma) of 1.7 nM. Furthermore, the proposed method was successfully intended for the determination of trace DA in human urine samples without the interference of other molecules and ions. PMID- 22672764 TI - A novel dual mode microelectrode array for neuroelectrical and neurochemical recording in vitro. AB - The communication between neurons is inherently electrical and chemical in nature. In situ, simultaneous acquisition for the dual mode signals is important for neuroscience research. In this paper, the concept of dual mode neural microelectrode array (MEA) sensor was proposed, and a low cost thin film MEA chip for in vitro test was fabricated using standard lithography technology. The sensor incorporates arrayed microelectrodes, a counter electrode and a reference electrode on one glass slide, which is suitable for electrophysiological and electrochemical recording in vitro. Electrophysiological recordings were carried out on acute hippocampus slice. Local field potentials and three different spike firing patterns with the amplitude ranging from +/- 20 MUV to +/- 60 MUV were acquired by the arrayed microelectrodes. Electrochemical current response of the microelectrodes to calibrated dopamine solution was tested. A good linear relationship between the current and dopamine concentration was observed, with the detection sensitivity of 4671 MUA mM(-1)cm(-2) and a correlation coefficient of 0.986. The sensor is novel for its capability of detecting in vitro dual mode neural signals on one single chip. PMID- 22672765 TI - A moving-part-free protamine-sensitive polymeric membrane electrode for sensitive biomedical analyses. AB - Traditional potentiometric polyion-sensitive electrodes can only work effectively in samples with vigorous convection fulfilled by magnetic stirrer, electrode rotator, or other moving components. The dependence on complex moving parts prohibits the fabrication of compact, cost-effective, and energy-effective test devices from the commercial point of view. In this paper, a novel potentiometric sensing protocol without using any moving parts has been proposed for polycationic protamine. In contrast to traditional protamine-sensitive electrodes conditioned by discriminated ion (Na(+)), the proposed electrode is conditioned with primary ion (protamine). Upon a medium exchange from the conditioning solution into an unstirred sample solution without protamine, protamine loaded in the membrane is stripped into the aqueous phase via ion exchange with aqueous sodium ion, thereby inducing a large potential drop. Interestingly, when the sample solution initially contains protamine, the ion-exchange process has been found to be sensitively inhibited by the sample protamine, and thus the potential drop is suppressed, which forms the basis of the moving-part-free potentiometric polyion sensing strategy. Utilizing the digestion ability of protease to protamine, the electrode was employed to determine the activity of trypsin with a detection limit at least one order of magnitude lower than traditional potentiometric methods. The trypsin inhibitor in both buffer and plasma samples was also sensitively detected with the moving-part-free protamine-sensitive electrode. Finally, the ability of the proposed electrode to detect polyanionic heparin was demonstrated. PMID- 22672766 TI - Increased NMDA receptor inhibition at an increased Sevoflurane MAC. AB - BACKGROUND: Sevoflurane potently enhances glycine receptor currents and more modestly decreases NMDA receptor currents, each of which may contribute to immobility. This modest NMDA receptor antagonism by sevoflurane at a minimum alveolar concentration (MAC) could be reciprocally related to large potentiation of other inhibitory ion channels. If so, then reduced glycine receptor potency should increase NMDA receptor antagonism by sevoflurane at MAC. METHODS: Indwelling lumbar subarachnoid catheters were surgically placed in 14 anesthetized rats. Rats were anesthetized with sevoflurane the next day, and a pre-infusion sevoflurane MAC was measured in duplicate using a tail clamp method. Artificial CSF (aCSF) containing either 0 or 4 mg/mL strychnine was then infused intrathecally at 4 MUL/min, and the post-infusion baseline sevoflurane MAC was measured. Finally, aCSF containing strychnine (either 0 or 4 mg/mL) plus 0.4 mg/mL dizocilpine (MK-801) was administered intrathecally at 4 MUL/min, and the post-dizocilpine sevoflurane MAC was measured. RESULTS: Pre-infusion sevoflurane MAC was 2.26%. Intrathecal aCSF alone did not affect MAC, but intrathecal strychnine significantly increased sevoflurane requirement. Addition of dizocilpine significantly decreased MAC in all rats, but this decrease was two times larger in rats without intrathecal strychnine compared to rats with intrathecal strychnine, a statistically significant (P < 0.005) difference that is consistent with increased NMDA receptor antagonism by sevoflurane in rats receiving strychnine. CONCLUSIONS: Glycine receptor antagonism increases NMDA receptor antagonism by sevoflurane at MAC. The magnitude of anesthetic effects on a given ion channel may therefore depend on the magnitude of its effects on other receptors that modulate neuronal excitability. PMID- 22672767 TI - Midline crossing is not required for subsequent pathfinding decisions in commissural neurons. AB - BACKGROUND: Growth cone navigation across the vertebrate midline is critical in the establishment of nervous system connectivity. While midline crossing is achieved through coordinated signaling of attractive and repulsive cues, this has never been demonstrated at the single cell level. Further, though growth cone responsiveness to guidance cues changes after crossing the midline, it is unclear whether midline crossing itself is required for subsequent guidance decisions in vivo. In the zebrafish, spinal commissures are initially formed by a pioneer neuron called CoPA (Commissural Primary Ascending). Unlike in other vertebrate models, CoPA navigates the midline alone, allowing for single-cell analysis of axon guidance mechanisms. RESULTS: We provide evidence that CoPA expresses the known axon guidance receptors dcc, robo3 and robo2. Using loss of function mutants and gene knockdown, we show that the functions of these genes are evolutionarily conserved in teleosts and that they are used consecutively by CoPA neurons. We also reveal novel roles for robo2 and robo3 in maintaining commissure structure. When midline crossing is prevented in robo3 mutants and dcc gene knockdown, ipsilaterally projecting neurons respond to postcrossing guidance cues. Furthermore, DCC inhibits Robo2 function before midline crossing to allow a midline approach and crossing. CONCLUSIONS: Our results demonstrate that midline crossing is not required for subsequent guidance decisions by pioneer axons and that this is due, in part, to DCC inhibition of Robo2 function prior to midline crossing. PMID- 22672768 TI - Topoisomerase expression in oral squamous cell carcinoma: relationship with cancer stem cells profiles and lymph node metastasis. AB - BACKGROUND: The relationship between predictive proteins and tumors presenting cancer stem cells (CSCs) profiles in oral tumors is still poorly understood. This study aims to identify the relationship between topoisomerases I, IIalpha, and IIIalpha and putative CSCs immunophenotype in oral squamous cell carcinoma (OSCC) and determine its influence on prognosis. METHODS: The following data were retrieved from 127 patients: age, gender, primary anatomic site, smoking and alcohol intake, recurrence, metastases, histologic classification, treatment, and survival. An immunohistochemical study for topoisomerases I, IIalpha, and IIIalpha was performed in a tissue microarray containing 127 paraffin blocks of OSCCs. RESULTS: In univariate analysis, topoisomerases expression showed significant differences according to CSCs profiles and p53 immunoexpression, but not with survival. Topoisomerases IIalpha and IIIalpha also showed significant relationship with lymph node metastasis. The multivariate test confirmed these associations. CONCLUSIONS: The results that all topoisomerases correlates with OSCC CSCs may indicate a role for topoisomerases in head and neck carcinogenesis. Notwithstanding, it is plausible that other members of topoisomerases family could represent novel therapeutical targets in oral squamous cell carcinoma. PMID- 22672769 TI - Melanoma recognition framework based on expert definition of ABCD for dermoscopic images. AB - BACKGROUND/PURPOSE: Melanoma Recognition based on clinical ABCD rule is widely used for clinical diagnosis of pigmented skin lesions in dermoscopy images. However, the current computer-aided diagnostic (CAD) systems for classification between malignant and nevus lesions using the ABCD criteria are imperfect due to use of ineffective computerized techniques. METHODS: In this study, a novel melanoma recognition system (MRS) is presented by focusing more on extracting features from the lesions using ABCD criteria. The complete MRS system consists of the following six major steps: transformation to the CIEL*a*b* color space, preprocessing to enhance the tumor region, black-frame and hair artifacts removal, tumor-area segmentation, quantification of feature using ABCD criteria and normalization, and finally feature selection and classification. RESULTS: The MRS system for melanoma-nevus lesions is tested on a total of 120 dermoscopic images. To test the performance of the MRS diagnostic classifier, the area under the receiver operating characteristics curve (AUC) is utilized. The proposed classifier achieved a sensitivity of 88.2%, specificity of 91.3%, and AUC of 0.880. CONCLUSIONS: The experimental results show that the proposed MRS system can accurately distinguish between malignant and benign lesions. The MRS technique is fully automatic and can easily integrate to an existing CAD system. To increase the classification accuracy of MRS, the CASH pattern recognition technique, visual inspection of dermatologist, contextual information from the patients, and the histopathological tests can be included to investigate the impact with this system. PMID- 22672770 TI - Safety and biomarker effects of solanezumab in patients with Alzheimer's disease. AB - OBJECTIVES: To assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of 12 weekly infusions of solanezumab, an anti-beta-amyloid (Abeta) antibody, in patients with mild-to-moderate Alzheimer's disease. Cognitive measures were also obtained. METHODS: In this phase 2, randomized, double-blind, placebo-controlled clinical trial, 52 patients with Alzheimer's disease received placebo or antibody (100 mg every 4 weeks, 100 mg weekly, 400 mg every 4 weeks, or 400 mg weekly) for 12 weeks. Safety and biomarker evaluations continued until 1 year after randomization. Both magnetic resonance imaging and cerebrospinal fluid (CSF) examinations were conducted at baseline and after the active treatment period. The Abeta concentrations were measured in plasma and CSF, and the Alzheimer's Disease Assessment Scale-cognitive portion was administered. RESULTS: Clinical laboratory values, CSF cell counts, and magnetic resonance imaging scans were unchanged by treatment, and no adverse events could be clearly related to antibody administration. Total (bound to antibody and unbound) Abeta(1-40) and Abeta(1-42) in plasma increased in a dose-dependent manner. Antibody treatment similarly increased total Abeta(1-40) and Abeta(1-42) in CSF. For patients taking 400 mg weekly, antibody treatment decreased unbound Abeta(1-40) in CSF (P < .01), but increased unbound Abeta(1-42) in CSF in a dose dependent manner. The Alzheimer's Disease Assessment Scale-cognitive portion was unchanged after the 12-week antibody administration. CONCLUSIONS: Antibody administration was well tolerated with doses up to 400 mg weekly. The dose dependent increase in unbound CSF Abeta(1-42) suggests that this antibody may shift Abeta equilibria sufficiently to mobilize Abeta(1-42) from amyloid plaques. PMID- 22672771 TI - Substrate effects on the strain relaxation in GaN/AlN short-period superlattices. AB - We present a comparative study of the strain relaxation of GaN/AlN short-period superlattices (SLs) grown on two different III-nitride substrates introducing different amounts of compensating strain into the films. We grow by plasma assisted molecular beam epitaxy (0001)-oriented SLs on a GaN buffer deposited on GaN(thick)-on-sapphire template and on AlN(thin)-on-sapphire template. The ex situ analysis of strain, crack formation, dislocation density, and microstructure of the SL layers has established that the mechanism of strain relaxation in these structures depends on the residual strain in substrate and is determined mainly by the lattice mismatch between layers. For growth on the AlN film, the compensating strain introduced by this film on the layer prevented cracking; however, the densities of surface pits and dislocations were increased as compared with growth on the GaN template. Three-dimensional growth of the GaN cap layer in samples with pseudomorphly grown SLs on the AlN template is observed. At the same time, two-dimensional step-flow growth of the cap layer was observed for structures with non-pseudomorphly grown SLs on the GaN template with a significant density of large cracks appearing on the surface. The growth mode of the GaN cap layer is predefined by relaxation degree of top SL layers. PMID- 22672772 TI - Short-term outcomes of extracorporeal shock wave therapy for the treatment of chronic non-calcific tendinopathy of the supraspinatus: a double-blind, randomized, placebo-controlled trial. AB - BACKGROUND: There is evidence supporting the use of extracorporeal shock wave therapy (ESWT) in calcific tendinopathy of the rotator cuff, but the best current evidence does not support its use in non-calcifying tendinopathy. We conducted a randomized placebo-controlled trial to investigate the efficacy and safety of low energy ESWT for non-calcifying tendinopathy of the rotator cuff. METHODS: 20 patients with non-calcifying supraspinatus tendinopathy (NCST) were randomized to an active or a sham treatment group. Physical, blood, roentgenographic, and MRI examinations of the shoulder were conducted to verify that patients met the inclusion and exclusion criteria. These examinations were repeated six and twelve weeks after treatments. Effectiveness was determined by comparison of the mean improvement in the Constant and Murley score (CMS) between the treatment and the placebo groups at three months. Safety was assessed by analyzing the number and severity of adverse events. RESULTS: All the patients completed the investigation protocol. At the final follow-up, significant improvement in the total CMS score and most of the CMS subscales was observed in the ESWT group when compared to the baseline values. Significantly higher total CMS, and significantly higher scores for CMS pain and ROM were observed in the ESWT group when compared to the placebo. No serious adverse events were noted after ESWT. CONCLUSIONS: Patients suffering from NCST may benefit from low energy ESWT, at least in short-term. The application protocol of ESWT is likely to play a key-role in a successful treatment. Future investigations should be undertaken on the long-term effects of this technique for the treatment of NCST. TRIAL REGISTRATION: Current Controlled Trials ISRCTN41236511. PMID- 22672773 TI - Clinical outcome and microvascular blood flow in VAC(r) - and Sorbalgon(r) treated peri-vascular infected wounds in the groin after vascular surgery - an early interim analysis. AB - Vacuum-assisted wound closure (VAC((r))) therapy is considered to be superior to conventional dressings in the treatment of peri-vascular groin infections after vascular surgery at our department. Therefore, we performed an early interim analysis of the clinical outcomes in these seriously ill patients at risk of amputation and death. Patients were randomised to either VAC((r)) (n = 5) or Sorbalgon((r)) (n = 5; best alternative treatment) therapy after surgical debridement. Non-invasive, laser Doppler perfusion imaging (LDPI) studies of the skin adjacent to the undressed wound were performed after 14 days of wound treatment. There was no difference in LDPI values in VAC((r)) versus Sorbalgon((r)) treated patients (P = 0.46). One patient in the VAC((r)) group suffered from two re-bleeding episodes, leading to vascular resection and transfemoral amputation and in the Sorbalgon((r)) group two had a complete wound healing time of more than 4 months and one had a visible interposition bypass graft in the groin after 1 month of treatment. No patient died of the groin infection. Although not statistically proven, fewer wound treatment failures were recorded in the VAC((r)) group, justifying this early interim analysis. LDPI studies were feasible. PMID- 22672774 TI - Optimization of iTRAQ labelling coupled to OFFGEL fractionation as a proteomic workflow to the analysis of microsomal proteins of Medicago truncatula roots. AB - BACKGROUND: Shotgun proteomics represents an attractive technical framework for the study of membrane proteins that are generally difficult to resolve using two dimensional gel electrophoresis. The use of iTRAQ, a set of amine-specific isobaric tags, is currently the labelling method of choice allowing multiplexing of up to eight samples and the relative quantification of multiple peptides for each protein. Recently the hyphenation of different separation techniques with mass spectrometry was used in the analysis of iTRAQ labelled samples. OFFGEL electrophoresis has proved its effectiveness in isoelectric point-based peptide and protein separation in solution. Here we describe the first application of iTRAQ-OFFGEL-LC-MS/MS on microsomal proteins from plant material. The investigation of the iTRAQ labelling effect on peptide electrofocusing in OFFGEL fractionator was carried out on Medicago truncatula membrane protein digests. RESULTS: In-filter protein digestion, with easy recovery of a peptide fraction compatible with iTRAQ labelling, was successfully used in this study. The focusing quality in OFFGEL electrophoresis was maintained for iTRAQ labelled peptides with a higher than expected number of identified peptides in basic OFFGEL-fractions. We furthermore observed, by comparing the isoelectric point (pI) fractionation of unlabelled versus labelled samples, a non-negligible pI shifts mainly to higher values. CONCLUSIONS: The present work describes a feasible and novel protocol for in-solution protein digestion in which the filter unit permits protein retention and buffer removal. The data demonstrates an impact of iTRAQ labelling on peptide electrofocusing behaviour in OFFGEL fractionation compared to their native counterpart by the induction of a substantial, generally basic pI shift. Explanations for the occasionally observed acidic shifts are likewise presented. PMID- 22672775 TI - Heat shock effects on seed germination of five Brazilian savanna species. AB - Fire is considered an important factor in influencing the physiognomy, dynamics and composition of Neotropical savannas. Species of diverse physiognomies exhibit different responses to fire, such as population persistence and seed mortality, according to the fire frequency to which they are submitted. The aim of this study is to investigate the effects of heat shocks on seed germination of Anadenanthera macrocarpa (Benth.) Brenan, Dalbergia miscolobium Benth., Aristolochia galeata Mart. & Zucc., Kielmeyera coriacea (Spreng.) Mart. and Guazuma ulmifolia Lam., which are native species of the Brazilian savanna. The temperatures and exposure times to which the seeds were submitted were established according to data obtained in the field during a prescribed fire: 60 degrees C (10, 20 and 40 min), 80 degrees C (5, 10 and 20 min) and 100 degrees C (2, 5 and 10 min). Untreated seeds were used as controls. Seeds of A. galeata and K. coriacea showed high tolerance to most heat treatments, and seeds of A. macrocarpa showed a significant reduction in germination percentage after treatments of 80 degrees C and 100 degrees C. Treatments of 100 degrees C for 10 min reduced germination percentage for all species except G. ulmifolia, which has dormant seeds. For this species, germination was accelerated by heat treatments. The high temperatures applied did not interfere with the time to 50% germination (T(50) ) of the tolerant seeds. Seeds of the savanna species K. coriacea and A. galeata were more tolerant to heat shocks than seeds of the forest species A. macrocarpa. Guazuma ulmifolia, the forest species with seeds that germinate after heat shock, also occurs in savanna physiognomies. Overall, the high temperatures applied did not affect the germination rate of the tolerant seeds. PMID- 22672776 TI - Centrality-based pathway enrichment: a systematic approach for finding significant pathways dominated by key genes. AB - BACKGROUND: Biological pathways are important for understanding biological mechanisms. Thus, finding important pathways that underlie biological problems helps researchers to focus on the most relevant sets of genes. Pathways resemble networks with complicated structures, but most of the existing pathway enrichment tools ignore topological information embedded within pathways, which limits their applicability. RESULTS: A systematic and extensible pathway enrichment method in which nodes are weighted by network centrality was proposed. We demonstrate how choice of pathway structure and centrality measurement, as well as the presence of key genes, affects pathway significance. We emphasize two improvements of our method over current methods. First, allowing for the diversity of genes' characters and the difficulty of covering gene importance from all aspects, we set centrality as an optional parameter in the model. Second, nodes rather than genes form the basic unit of pathways, such that one node can be composed of several genes and one gene may reside in different nodes. By comparing our methodology to the original enrichment method using both simulation data and real world data, we demonstrate the efficacy of our method in finding new pathways from biological perspective. CONCLUSIONS: Our method can benefit the systematic analysis of biological pathways and help to extract more meaningful information from gene expression data. The algorithm has been implemented as an R package CePa, and also a web-based version of CePa is provided. PMID- 22672777 TI - Soluble amyloid precursor protein alpha in the cerebrospinal fluid as a diagnostic and prognostic biomarker for idiopathic normal pressure hydrocephalus. AB - BACKGROUND: Cognitive impairment is difficult to improve after shunt operation in patients with idiopathic normal pressure hydrocephalus (iNPH). This study aims to identify cerebrospinal fluid (CSF) biomarkers predictive of improvement in cognitive function. METHODS: This study was conducted between January 2008 and December 2010 on consecutive, unselected admissions to our program for the treatment of patients with clinically suspected iNPH. Lumbar CSF concentrations of total tau (Tau), tau phosphorylated at threonine 181 (p-tau), soluble amyloid precursor protein (sAPP), sAPPalpha, sAPPbeta, and beta-amyloid(1-42) (Abeta42) were analyzed by ELISA. RESULTS: Concentrations of p-tau, sAPP, sAPPalpha, and sAPPbeta were strong diagnostic biomarkers for distinguishing between iNPH and Alzheimer's disease (AD). sAPPalpha exhibited the highest accuracy in differentiating iNPH from patients with AD and normal controls, with an area under the curve value of 0.994. We examined the prognostic value of p-tau and sAPPalpha for cognition function after surgery. With a cutoff value of 198 ng/ml or less for sAPPalpha, sensitivity and specificity are 66.7% and 82.9%, respectively, whilst the Mini-Mental State Examination score at 6 months after surgery is expected to be 25 or more. CONCLUSION: Our results show that sAPPalpha is a suitable biomarker for the diagnosis and prognosis of iNPH. PMID- 22672779 TI - Evaluation epidermal p53 immunostaining by digital image analysis. AB - BACKGROUND/PURPOSE: Digital techniques have been developed and validated to assess semiquantitatively immunohistochemical nuclear staining. Currently visual classification is the standard for qualitative nuclear evaluation. Analysis of pixels that represents the immunohistochemical labeling can be more sensitive, reproducible and objective than visual grading. This study compared two semiquantitative techniques of digital image analysis with three techniques of visual analysis imaging to estimate the p53 nuclear immunostaining. METHODS: Sixty-three sun-exposed forearm-skin biopsies were photographed and submitted to three visual analyses of images: the qualitative visual evaluation method (0 to 4 + ), the percentage of labeled nuclei and HSCORE. Digital image analysis was performed using ImageJ 1.45p; the density of nuclei was scored per ephitelial area (DensNU) and the pixel density was established in marked suprabasal epithelium (DensPSB). RESULTS: Statistical significance was found in: the agreement and correlation among the visual estimates of evaluators, correlation among the median visual score of the evaluators, the HSCORE and the percentage of marked nuclei with the DensNU and DensPSB estimates. DensNU was strongly correlated to the percentage of p53-marked nuclei in the epidermis, and DensPSB with the HSCORE. CONCLUSION: The parameters presented herein can be applied in routine analysis of immunohistochemical nuclear staining of epidermis. PMID- 22672780 TI - Photocurrent detection of chemically tuned hierarchical ZnO nanostructures grown on seed layers formed by atomic layer deposition. AB - We demonstrate the morphological control method of ZnO nanostructures by atomic layer deposition (ALD) on an Al2O3/ZnO seed layer surface and the application of a hierarchical ZnO nanostructure for a photodetector. Two layers of ZnO and Al2O3 prepared using ALD with different pH values in solution coexisted on the alloy film surface, leading to deactivation of the surface hydroxyl groups. This surface complex decreased the ZnO nucleation on the seed layer surface, and thereby effectively screened the inherent surface polarity of ZnO. As a result, a 2-D zinc hydroxyl compound nanosheet was produced. With increasing ALD cycles of ZnO in the seed layer, the nanostructure morphology changes from 2-D nanosheet to 1-D nanorod due to the recovery of the natural crystallinity and polarity of ZnO. The thin ALD ZnO seed layer conformally covers the complex nanosheet structure to produce a nanorod, then a 3-D, hierarchical ZnO nanostructure was synthesized using a combined hydrothermal and ALD method. During the deposition of the ALD ZnO seed layer, the zinc hydroxyl compound nanosheets underwent a self-annealing process at 150 degrees C, resulting in structural transformation to pure ZnO 3-D nanosheets without collapse of the intrinsic morphology. The investigation on band electronic properties of ZnO 2-D nanosheet and 3-D hierarchical structure revealed noticeable variations depending on the richness of Zn-OH in each morphology. The improved visible and ultraviolet photocurrent characteristics of a photodetector with the active region using 3-D hierarchical structure against those of 2-D nanosheet structure were achieved. PMID- 22672778 TI - Predicting later-life outcomes of early-life exposures. AB - BACKGROUND: In utero exposure of the fetus to a stressor can lead to disease in later life. Epigenetic mechanisms are likely mediators of later-life expression of early-life events. OBJECTIVES: We examined the current state of understanding of later-life diseases resulting from early-life exposures in order to identify in utero and postnatal indicators of later-life diseases, develop an agenda for future research, and consider the risk assessment implications of this emerging knowledge. METHODS: This review was developed based on our participation in a National Research Council workshop titled "Use of in Utero and Postnatal Indicators to Predict Health Outcomes Later in Life: State of the Science and Research Recommendations." We used a case study approach to highlight the later life consequences of early-life malnutrition and arsenic exposure. DISCUSSION: The environmental sensitivity of the epigenome is viewed as an adaptive mechanism by which the developing organism adjusts its metabolic and homeostatic systems to suit the anticipated extrauterine environment. Inappropriate adaptation may produce a mismatch resulting in subsequent increased susceptibility to disease. A nutritional mismatch between the prenatal and postnatal environments, or early life obesogen exposure, may explain at least some of the recent rapid increases in the rates of obesity, type 2 diabetes, and cardiovascular diseases. Early-life arsenic exposure is also associated with later-life diseases, including cardiovascular disease and cancer. CONCLUSIONS: With mounting evidence connecting early-life exposures and later-life disease, new strategies are needed to incorporate this emerging knowledge into health protective practices. PMID- 22672781 TI - The greatest risk for low-back pain among newly educated female health care workers; body weight or physical work load? AB - BACKGROUND: Low back pain (LBP) represents a major socioeconomic burden for the Western societies. Both life-style and work-related factors may cause low back pain. Prospective cohort studies assessing risk factors among individuals without prior history of low back pain are lacking. This aim of this study was to determine risk factors for developing low back pain (LBP) among health care workers. METHODS: Prospective cohort study with 2,235 newly educated female health care workers without prior history of LBP. Risk factors and incidence of LBP were assessed at one and two years after graduation. RESULTS: Multinomial logistic regression analyses adjusted for age, smoking, and psychosocial factors showed that workers with high physical work load had higher risk for developing LBP than workers with low physical work load (OR 1.8; 95% CI 1.1-2.8). In contrast, workers with high BMI were not at a higher risk for developing LBP than workers with a normal BMI. CONCLUSION: Preventive initiatives for LBP among health care workers ought to focus on reducing high physical work loads rather than lowering excessive body weight. PMID- 22672782 TI - Non-invasive assessment of negative pressure wound therapy using high frequency diagnostic ultrasound: oedema reduction and new tissue accumulation. AB - Tissue oedema plays an important role in the pathology of chronic and traumatic wounds. Negative pressure wound therapy (NPWT) is thought to contribute to active oedema reduction, yet few studies have showed this effect. In this study, high frequency diagnostic ultrasound at 20 MHz with an axial resolution of 60 um was used to assess the effect of NPWT at - 80 mmHg on pressure ulcers and the surrounding tissue. Wounds were monitored in four patients over a 3-month period during which changes in oedema and wound bed thickness (granulation tissue) were measured non-invasively. The results showed a rapid reduction of periwound tissue oedema in all patients with levels falling by a mean of 43% after 4 days of therapy. A 20% increase in the thickness of the wound bed was observed after 7 days due to new granulation tissue formation. Ultrasound scans through the in situ gauze NPWT filler also revealed the existence of macrodeformation in the tissue produced by the negative pressure. These preliminary studies suggest that non-invasive assessment using high frequency diagnostic ultrasound could be a valuable tool in clinical studies of NPWT. PMID- 22672783 TI - Validity and reliability of the Korean version of the pediatric quality of life ESRD module. AB - BACKGROUND: Health-related quality of life is a very important issue in children with end-stage renal disease and their family. Moreover, this can be a lifelong problem. In this study, we performed a cross-sectional investigation of the health-related quality of life in Korean children, undergoing renal replacement therapies, such as dialysis and renal transplantation. FINDINGS: We validated the Korean version of the PedsQL 3.0 End-Stage Renal Disease Module by comparing with the PedsQL 4.0 Generic Core Scales. A total of 92 pediatric patients with end stage renal disease, aged 2-18 year old, were enrolled in four teaching hospitals in Korea. The module was acceptable for both parent proxy-report and child self report. The response rate was acceptable, since no reminders were delivered. A large proportion of the responders answered > 90% of the items, which suggests a good face validity. The PedsQL 4.0 Generic Core Scales and the PedsQL 3.0 End Stage Renal Disease Module showed minimal missing values in the current study, which supported feasibility. The validation analyses revealed acceptable floor and ceiling effects and an acceptable construct validity. CONCLUSIONS: The PedsQL 3.0 End-stage Renal Disease Module may be useful as an end-stage renal disease specific instrument in the evaluation of the health-related quality of life in Korean children; however, a larger, longitudinal prospective study is needed. PMID- 22672784 TI - Variations in foliar stable carbon isotopes among functional groups and along environmental gradients in China - a meta-analysis. AB - Variations in foliar stable carbon isotope signatures (delta(13)C) of different plant functional groups (PFGs) and their relationships with environmental factors in China were investigated in this meta-analysis. There were some significant, but small differences in delta(13)C among PFGs categorised by life form (<10/00). Trees (-26.780/00) and shrubs (-26.890/00) had similar mean delta(13)C that were significantly higher than those of herbs (-27.490/00). Evergreen shrubs ( 25.820/00) had significantly higher mean delta(13)C than deciduous shrubs ( 26.920/00). Perennial herbs (-26.830/00) had significantly higher mean delta(13) C than annual herbs (-27.100/00). Grasses (-26.460/00) had significantly higher mean delta(13)C than forbs (-26.960/00). For pooled data, delta(13)C was significantly and negatively correlated with mean annual precipitation (MAP) and mean annual temperature (MAT), while it was significantly and positively correlated with latitude and altitude. There was a threshold value of MAP along the gradients, and delta(13)C did not change significantly with higher rainfall. The delta(13) C of PFGs changed with altitude, suggesting that increases in delta(13)C with altitude cannot be generalised. Differences in delta(13)C between PFGs were generally much <10/00 and therefore insignificant. In contrast, MAP and MAT had relatively large effects on delta(13) C (more than 40/00 between extremes). The delta(13)C of some PFGs responded to environmental gradients in the same manner, while their 'rates' of change were significantly different in some cases. This information could help predict potential changes in the distribution of PFGs in response to future climate change. PMID- 22672785 TI - Analyzing fixed points of intracellular regulation networks with interrelated feedback topology. AB - BACKGROUND: Modeling the dynamics of intracellular regulation networks by systems of ordinary differential equations has become a standard method in systems biology, and it has been shown that the behavior of these networks is often tightly connected to the network topology. We have recently introduced the circuit-breaking algorithm, a method that uses the network topology to construct a one-dimensional circuit-characteristic of the system. It was shown that this characteristic can be used for an efficient calculation of the system's fixed points. RESULTS: Here we extend previous work and show several connections between the circuit-characteristic and the stability of fixed points. In particular, we derive a sufficient condition on the characteristic for a fixed point to be unstable for certain graph structures and demonstrate that the characteristic does not contain the information to decide whether a fixed point is asymptotically stable. All statements are illustrated on biological network models. CONCLUSIONS: Single feedback circuits and their role for complex dynamic behavior of biological networks have extensively been investigated, but a transfer of most of these concepts to more complex topologies is difficult. In this context, our algorithm is a powerful new approach for the analysis of regulation networks that goes beyond single isolated feedback circuits. PMID- 22672786 TI - The fraction of recombinant factor VIII:Ag unable to bind von Willebrand factor has no FVIII coagulant activity: studies in vitro. AB - A fraction of FVIII:Ag in commercial recombinant FVIII (rFVIII) cannot bind VWF whereas all the FVIII:Ag in plasma-derived FVIII (pd-FVIII) concentrates does. To compare the FVIII:C activities of the fractions of rFVIII:Ag that can and cannot bind VWF. The FVIII:Ag contents of the rFVIII Kogenate, and Advate and a pd-FVIII pd-VWF (Fanhdi) were measured by ELISA. The FX activation was initiated by adding 1.0 IU of FVIII:C of each FVIII-containing product to a coagulant phospholipids suspension containing 1.0 nm FIXa, 100 nm FX, 1 MUm hirudin and 2 mm calcium chloride and measured after 1, 5 and 10 min. The same approach was followed after adding 2.0 IU of pd-VWF to 1.0 IU of FVIII:C of Kogenate or Advate. The FVIII:Ag content/IU of FVIII:C of Kogenate, Advate and Fanhdi were 1.80 +/- 0.05, 1.31 +/- 0.9 and 0.84 +/- 1.5 IU respectively. Only Kogenate and Advate effectively enhanced FX activation 1 min after adding each FVIII:C to the coagulant suspension containing FIXa and FX. Thus, the FXa initially generated by FIXa readily activated FVIII:C in control Kogenate and Advate to thereby effectively enhance FX activation while the VWF in Fanhdi continued to suppress FX activation for up to 10 min. Addition of pd-VWF to Kogenate or Advate effectively decreased their enhancements of FX activation to the same level as Fanhdi over 10 min. The FVIII:Ag fraction in Kogenate and Advate that cannot bind VWF appears to be inactive as it has no measureable FVIII:C activity in the presence of added VWF in vitro. PMID- 22672787 TI - Improving the diagnostic accuracy of dysplastic and melanoma lesions using the decision template combination method. AB - BACKGROUND/PURPOSE: Melanoma is the most dangerous type of skin cancer, and early detection of suspicious lesions can decrease the mortality rate of this cancer. In this article, we present a multi-classifier system for improving the diagnostic accuracy of melanoma and dysplastic lesions based on the decision template combination rule. METHODS: First, the lesion is differentiated from the surrounding healthy skin in an image. Next, shape, colour and texture features are extracted from the lesion image. Different subsets of these features are fed to three different classifiers: k-nearest neighbour (k-NN), support vector machine (SVM) and linear discriminant analysis (LDA). The decision template method is used to combine the outputs of these classifiers. RESULTS: The proposed method has been evaluated on a set of 436 dermatoscopic images of benign, dysplastic and melanoma lesions. The final classifier ensemble delivers a total classification accuracy of 80.46%, with 67.73% of dysplastic lesions correctly classified and 83.53% of melanoma lesions correctly classified. CONCLUSION: The results show that the proposed method significantly increases the diagnostic accuracy of dysplastic and melanoma lesions compared with a single classifier. The total classification rate is also improved. PMID- 22672788 TI - Quantum dot-doped porous silicon metal-semiconductor metal photodetector. AB - In this paper, we report on the enhancement of spectral photoresponsivity of porous silicon metal-semiconductor metal (PS-MSM) photodetector embedded with colloidal quantum dots (QDs) inside the pore layer. The detection efficiency of QDs/PS hybrid-MSM photodetector was enhanced by five times larger than that of the undoped PS-MSM photodetector. The bandgap alignment between PS (approximately 1.77 eV) and QDs (approximately 1.91 eV) facilitates the photoinduced electron transfer from QDs to PS whereby enhancing the photoresponsivity. We also showed that the photoresponsitivity of QD/PS hybrid-MSM photodetector depends on the number of layer coatings of QDs and the pore sizes of PS. PMID- 22672789 TI - Phthalate exposure changes the metabolic profile of cardiac muscle cells. AB - BACKGROUND: Phthalates are common plasticizers present in medical-grade plastics and other everyday products. They can also act as endocrine-disrupting chemicals and have been linked to the rise in metabolic disorders. However, the effect of phthalates on cardiac metabolism remains largely unknown. OBJECTIVES: We examined the effect of di(2-ethylhexyl)phthalate (DEHP) on the metabolic profile of cardiomyocytes because alterations in metabolic processes can lead to cell dysfunction. METHODS: Neonatal rat cardiomyocytes were treated with DEHP at a concentration and duration comparable to clinical exposure (50-100 MUg/mL, 72 hr). We assessed the effect of DEHP on gene expression using microarray analysis. Physiological responses were examined via fatty acid utilization, oxygen consumption, mitochondrial mass, and Western blot analysis. RESULTS: Exposure to DEHP led to up-regulation of genes associated with fatty acid transport, esterification, mitochondrial import, and beta-oxidation. The functional outcome was an increase in myocyte fatty acid-substrate utilization, oxygen consumption, mitochondrial mass, PPARalpha (peroxisome proliferator-activated receptor alpha) protein expression, and extracellular acidosis. Treatment with a PPARalpha agonist (Wy-14643) only partially mimicked the effects observed in DEHP-treated cells. CONCLUSIONS: Data suggest that DEHP exposure results in metabolic remodeling of cardiomyocytes, whereby cardiac cells increase their dependence on fatty acids for energy production. This fuel switch may be regulated at both the gene expression and posttranscription levels. Our findings have important clinical implications because chronic dependence on fatty acids is associated with an accumulation in lipid intermediates, lactate, protons, and reactive oxygen species. This dependence can sensitize the heart to ischemic injury and ventricular dysfunction. PMID- 22672790 TI - Electrocardiographic changes of ST-elevation myocardial infarction in patients with complete occlusion of the left main trunk without collateral circulation: differential diagnosis and clinical considerations. AB - Acute coronary syndromes due to involvement of the left main trunk usually present with subtotal occlusion and electrocardiographic pattern with predominant ST depression (non-ST-elevation myocardial infarction). The cases with complete occlusion frequently present an ST-elevation myocardial infarction pattern, but these patients usually die before reaching the hospital. We present a series of 7 patients with total left main trunk occlusion without collateral circulation showing ST-elevation myocardial infarction pattern. The electrocardiographic pattern is similar to left anterior descending coronary artery proximal occlusion to first septal and first diagonal but without ST elevation in V(1) and aVR because of left circumflex coronary artery compromise. In 4 (60%) of 7 of cases, there is also advanced right bundle-branch block plus superoanterior hemiblock. Despite severe clinical state at entrance (5/7 presented cardiac arrest/cardiogenic shock), 3 patients (43%) survived after percutaneous coronary intervention. PMID- 22672791 TI - Effects of flecainide therapy on inappropriate shocks and arrhythmias in catecholaminergic polymorphic ventricular tachycardia. AB - We report the case of a child with catecholaminergic polymorphic ventricular tachycardia, who had inappropriate electric shocks by an implantable cardioverter defibrillator and from recurrence of arrhythmias despite an appropriate beta blocking treatment. An additional treatment by flecainide completely suppressed inappropriate shocks due to sinusal tachycardia and ventricular tachyarrhythmias. We briefly discuss the potentially interesting effect of flecainide in this specific arrhythmia. PMID- 22672792 TI - Silicone lymphadenopathy: an unexpected cause of neck lumps. AB - OBJECTIVE: To report a rare case of silicone lymphadenopathy solely affecting the left supraclavicular lymph nodes. CASE REPORT: Our patient presented with a painless swelling in the left supraclavicular region. Notably, she had previously undergone cosmetic breast augmentation using silicone-containing implants. Radiological imaging and subsequent excisional biopsy of the swelling produced findings consistent with a silicone foreign body reaction secondary to bilateral breast implant rupture. CONCLUSION: Silicone lymphadenopathy following breast augmentation primarily affects the axillary nodes. Supraclavicular lymph node involvement is unusual. To our knowledge, this is the first report in the English language literature of silicone lymphadenopathy manifesting solely in the supraclavicular lymph nodes. Although the need to exclude malignancy in such cases is of the utmost importance, silicone lymphadenopathy should also be considered in the differential diagnosis. Fine needle aspiration cytology is a useful initial investigation, which may be followed up by excisional biopsy and histological analysis for further confirmatory diagnostic information. PMID- 22672793 TI - Time perspective and psychosocial positive functioning among Italian adolescents who binge eat and drink. AB - Evidence of an association between binge eating and binge drinking and of related health consequences have stimulated investigators to examine and explore risk and protective factors plus the reasons why individuals engage in these risky behaviours (Benjamin & Wulfert, 2003; Ferriter & Ray, 2011). This study examined the relationship between binge drinking and eating, time perspective and psychological functioning. A cross-sectional survey of 1350 17-19 year-old adolescents was conducted. Findings suggested that adolescents engaged in both binge eating and binge drinking behaviours reported negative experiences in the past, and they showed a lower future orientation and a greater inclination to fatalism than did the other students Additionally, they were more likely to report lower feelings of satisfaction with life and self-esteem than the others. The pattern of results allows to conclude that time perspective may be a salient dimension when exploring the psychosocial correlates of binge behaviours, particularly within adolescents. PMID- 22672794 TI - I-ONE therapy in patients undergoing total knee arthroplasty: a prospective, randomized and controlled study. AB - BACKGROUND: Total knee arthroplasty (TKA) is often associated with a severe local inflammatory reaction which, unless controlled, leads to persistent pain up to one year after surgery. Standard and accelerated rehabilitation protocols are currently being implemented after TKA, but no consensus exists regarding the long term effects. Biophysical stimulation with pulsed electromagnetic fields (PEMFs) has been demonstrated to exert an anti-inflammatory effect, to promote early functional recovery and to maintain a positive long-term effect in patients undergoing joint arthroscopy. The aim of this study was to evaluate whether PEMFs can be used to limit the pain and enhance patient recovery after TKA. METHODS: A prospective, randomized, controlled study in 30 patients undergoing TKA was conducted. Patients were randomized into experimental PEMFs or a control group. Patients in the experimental group were instructed to use I-ONE stimulator 4hours/day for 60days. Postoperatively, all patients received the same rehabilitation program. Treatment outcome was assessed using the Knee Society Score, SF-36 Health-Survey and VAS. Patients were evaluated pre-operatively and one, two, six and 12 months after TKA. Joint swelling and Non Steroidal Anti Inflammatory Drug (NSAID) consumption were recorded. Comparisons between the two groups were carried out using a two-tail heteroschedastic Student's t-test. Analysis of variance for each individual subject during the study was performed using ANOVA for multiple comparisons, applied on each group, and a Dunnet post hoc test. A p value < 0.05 was considered statistically significant. RESULTS: Pre operatively, no differences were observed between groups in terms of age, sex, weight, height, Knee-Score, VAS, SF-36 and joint swelling, with the exception of the Functional Score. The Knee-Score, SF-36 and VAS demonstrated significantly positive outcomes in the I-ONE stimulated group compared with the controls at follow-ups. In the I-ONE group, NSAID use was reduced and joint swelling resolution was more rapid than in controls. The effect of I-ONE therapy was maintained after use of the device was discontinued. CONCLUSIONS: The results of the study show early functional recovery in the I-ONE group. I-ONE therapy should be considered after TKA to prevent the inflammatory reaction elicited by surgery, for pain relief and to speed functional recovery. PMID- 22672796 TI - Synthesis and positive inotropic evaluation of N-(1-oxo-1,2,4,5-tetrahydro [1,2,4]triazolo[4,3-a]quinolin-7-yl)acetamides bearing piperazine and 1,4 diazepane moieties. AB - Two series of N-(1-oxo-1,2,4,5-tetrahydro-[1,2,4]triazolo[4,3-a]quinolin-7 yl)acetamides bearing piperazine and 1,4-diazepane moieties were synthesized and screened for their positive inotropic activity by measuring left atrium stroke volume on isolated rabbit heart preparations. Most of the derivatives exhibited better in vitro positive inotropic activity than the existing drug, milrinone, among which 2-(4-(4-chlorobenzyl)-1,4-diazepan-1-yl)-N-(1-oxo-1,2,4,5-tetrahydro [1,2,4]triazolo[4,3-a]quinolin-7-yl)acetamide 6c proved to be the most potent with 15.48 +/- 0.27% increased stroke volume (milrinone: 2.46 +/- 0.07%) at a concentration of 3 * 10(-5) M. The chronotropic effects of the compounds that exhibited inotropic effects were also evaluated. PMID- 22672795 TI - Extraction of DNA from plant and fungus tissues in situ. AB - BACKGROUND: When samples are collected in the field and transported to the lab, degradation of the nucleic acids contained in the samples is frequently observed. Immediate extraction and precipitation of the nucleic acids reduces degradation to a minimum, thus preserving accurate sequence information. An extraction method to obtain high quality DNA in field studies is described. FINDINGS: DNA extracted immediately after sampling was compared to DNA extracted after allowing the sampled tissues to air dry at 21 degrees C for 48 or 72 hours. While DNA extracted from fresh tissues exhibited little degradation, DNA extracted from all tissues exposed to 21 degrees C air for 48 or 72 hours exhibited varying degrees of degradation. Yield was higher for extractions from fresh tissues in most cases. Four microcentrifuges were compared for DNA yield: one standard electric laboratory microcentrifuge (max rcf = 16,000 * g), two battery-operated microcentrifuges (max rcf = 5,000 and 3,000 * g), and one manually-operated microcentrifuge (max rcf = 120 * g). Yields for all centrifuges were similar. DNA extracted under simulated field conditions was similar in yield and quality to DNA extracted in the laboratory using the same equipment. CONCLUSIONS: This CTAB (cetyltrimethylammonium bromide) DNA extraction method employs battery-operated and manually-operated equipment to isolate high quality DNA in the field. The method was tested on plant and fungus tissues, and may be adapted for other types of organisms. The method produced high quality DNA in laboratory tests and under simulated field conditions. The field extraction method should prove useful for working in remote sites, where ice, dry ice, and liquid nitrogen are unavailable; where degradation is likely to occur due to the long distances between the sample site and the laboratory; and in instances where other DNA preservation and transportation methods have been unsuccessful. It may be possible to adapt this method for genomic, metagenomic, transcriptomic and metabolomic projects using samples collected in situ. PMID- 22672797 TI - 8-17 DNAzyme modified with purine analogs in its catalytic core: the conservation of the five-membered moieties of purine residues. AB - 8-17 DNAzyme is characterized by its recurrence in different in vitro selections and versatile cleavage sites, leading to extensive studies on its structural properties and applications. We evaluated the purine residues (A6, G7, G11, A12, G14, and A15) in the catalytic core of 8-17 DNAzyme of their five-membered ring moiety with purine analogs 1-5 to have an insight into the conservation of the residues at the level of functional groups. The 7-nitrogen atom in the AGC loop was demonstrated to be strictly conserved for the cleavage reaction. But such modifications exerted favorable effect at G11 of the base-pair stem and A12 in the single-strand loop, directing toward more efficient DNAzymes. Even the most conserved G14 could tolerate such modifications. These results demonstrated that chemical modification on the functional groups is a feasible approach to gain an insight into the structural requirement in the catalytic reaction of DNAzymes. It also provided modification sites for introduction of signaling molecules used for mechanistic and folding studies of 8-17 DNAzyme. PMID- 22672798 TI - A new 9,11-secosterol from the soft coral Sinularia granosa. AB - Chemical investigations on the EtOAc-soluble fractions from the EtOH extract of Formosa soft coral afforded a new 9,11-secosteroid, 8alphaH-3beta,11-dihydroxy 5alpha,6alpha-expoxy-24-methylene-9,11-secocholestan-9-one (1), along with one known steroid 3beta,11-dihydroxy-5beta,6beta-expoxy-24-methylene-9,11 secocholestan-9-one (2) from Sinularia granosa. The structure of the new metabolite was elucidated on the basis of extensive spectroscopic analysis and by comparison of their NMR data with the known compounds, including 2. Both 1 and 2 were shown to significantly inhibit the accumulation of the pro-inflammatory inducible nitric oxide synthase protein, and 1 also was found to effectively reduce the level of cyclooxygenase-2 protein, in lipopolysaccharide-stimulated RAW264.7 macrophage cells at 10 MUM. Furthermore, cytotoxic activity of 1 and 2 toward a limited panel of cancer cell lines was also discovered. PMID- 22672799 TI - Potent and selective inhibitors of PI3Kdelta: obtaining isoform selectivity from the affinity pocket and tryptophan shelf. AB - A potent inhibitor of PI3Kdelta that is >= 200 fold selective for the remaining three Class I PI3K isoforms and additional kinases is described. The hypothesis for selectivity is illustrated through structure activity relationships and crystal structures of compounds bound to a K802T mutant of PI3Kgamma. Pharmacokinetic data in rats and mice support the use of 3 as a useful tool compound to use for in vivo studies. PMID- 22672800 TI - Makomotindoline from Makomotake, Zizania latifolia infected with Ustilago esculenta. AB - Makomotindoline (1) was isolated from Makomotake, Zizania latifolia infected with Ustilago esculenta. The structure was determined by the interpretation of spectroscopic data and synthesis. Makomotindoline (1), its l-Glc isomer (2) and its aglycon (3) were synthesized and their effects on rat glioma cells showed adverse effects on the cell growth. PMID- 22672801 TI - Synthesis and biological evaluation of antifungal derivatives of enfumafungin as orally bioavailable inhibitors of beta-1,3-glucan synthase. AB - Orally bioavailable inhibitors of beta-(1,3)-D-glucan synthase have been pursued as new, broad-spectrum fungicidal therapies suitable for treatment in immunocompromised patients. Toward this end, a collaborative medicinal chemistry program was established based on semisynthetic derivatization of the triterpenoid glycoside natural product enfumafungin in order to optimize in vivo antifungal activity and oral absorption properties. In the course of these studies, it was hypothesized that the pharmacokinetic properties of the semisynthetic enfumafungin analog 3 could be improved by tethering the alkyl groups proximal to the basic nitrogen of the C3-aminoether side chain into an azacyclic system, so as to preclude oxidative N-demethylation. The results of this research effort are disclosed herein. PMID- 22672802 TI - Sentulic acid: a cytotoxic ring A-seco triterpenoid from Sandoricum koetjape Merr. AB - A new ring A-seco triterpenoid, sentulic acid, along with a known oleanane-type triterpenoid, 3-oxoolean-12-en-27-oic acid, were isolated from the Indonesian plant Sandoricum koetjape Merr. Their chemical structures were elucidated by spectroscopic analysis. In addition, the cytotoxic effects of these compounds on human promyelocytic leukemia HL-60 cells were studied. The results of 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays and trypan blue dye exclusion tests showed that sentulic acid and 3-oxoolean-12-en-27-oic acid were able to induce cytotoxicity in these cells. Furthermore, morphological examination and DNA fragmentation analysis indicated that these cytotoxic effects were mediated by apoptosis. PMID- 22672803 TI - Design, synthesis and biological evaluation of novel imidazopyridines as potential antidiabetic GSK3beta inhibitors. AB - Design, synthesis and biological evaluation of the imidazopyridine analogs as novel GSK3beta inhibitors for treatment of type 2 diabetes mellitus are described. Most of the analogs exhibited excellent inhibitory activities (IC50<44 nM) against glycogen synthase kinase 3beta (GSK3beta). The structure-activity relationship (SAR) of the imidazopyridine analogs and the binding mode of analog 23 in the catalytic domain of GSK3beta, based on our X-ray crystallography study, are described. In particular, analog 28, which was selected as a potential drug candidate for treatment of type 2 diabetes mellitus, exhibited excellent GSK3beta inhibition, pharmacokinetic profiles and blood glucose lowering effect in mouse. PMID- 22672804 TI - Pyrrolidine based chiral organocatalyst for efficient asymmetric Michael addition of cyclic ketones to beta-nitrostyrenes. AB - An efficient asymmetric Michael addition of cyclic ketones to beta-nitrostyrenes using secondary diamine as an organocatalyst derived from l-proline and (R)-alpha methylbenzyl amine has been described. This pyrrolidine based catalyst 1 was found to be very effective to synthesize various gamma-nitrocarbonyl compounds in good yield (up to 81%) with excellent stereoselectivity (up to >99:1 dr and >99% ee). PMID- 22672805 TI - Immunohistochemical markers for the differential diagnosis of nephrogenic adenomas. AB - Nephrogenic adenoma (NA) is a rare benign lesion commonly occurring in the urinary bladder that poses challenges to devising a diagnosis. In this study, 21 cases of NAs were studied by performing immunohistochemistry for PAX8, p63, CK903, PSA, S100A1, BerEP4, and CEA on routine tissue sections. PAX8 showed diffuse moderate to strong (2+ and 3+) nuclear staining in all of NAs (n = 6 and 15, respectively) and negative in the normal urothelium (n = 15). Nuclear staining for p63 was not seen in any case of NAs examined (n = 19) and was diffuse and strong (3+) in the normal urothelium (n = 14). High-molecular-weight keratin CK903 showed weak (1+) diffuse staining in all of the NAs examined (n = 19) and diffuse and moderate to strong positivity in the normal urothelium (n = 16). PSA staining was negative in both of the NAs (n = 21) and normal urothelium (n = 16). S100A1 showed strong (3+) diffuse staining in 19 of 20 of the NAs examined (n = 19) and diffuse weak (1+) (n = 14) to moderate (n = 3) staining in the normal urothelium. BerEP4 showed focal to diffuse, mild to moderate (1+ and 2+) cytoplasmic staining in all of NAs (n = 2 and 19) and negative in the normal urothelium (n = 19). CEA staining was negative in both of the NAs (n = 21) and normal urothelium (n = 17). A panel composed of PAX8, p63, PSA, S100A1, and CEA appears to be sensitive and specific in differentiating NA from its mimics of urothelial and prostatic origins. PMID- 22672806 TI - Papillary squamous cell carcinoma of the oral mucosa: a clinicopathologic and immunohistochemical study of 12 cases and literature review. AB - Papillary squamous cell carcinoma (SCC) (PSCC) of the oral mucosa is a relatively rare but distinct variant of SCC of head and neck. The objectives of this study were to describe the clinicopathologic and immunohistochemical features of a series of patients with oral PSCC and to review the literature on this topic. Retrospective review of patients with clinical and pathologic diagnosis of PSCC (n = 12) between 2000 and 2008 in our institution was conducted. The outcome analysis in a mean follow-up of 56 months (range, 24-131 months) was performed. These patients were 7 women and 5 men, and the mean age at diagnosis was 72.9 years (range, 53-83 years). The cheek and the gingiva were the predominant sites of involvement. At the end of follow-up, 4 patients were found to have local recurrence, and 3 were dead of disease. The estimated 3- and 5-year survival was 91.7% and 76.4% for the whole series, respectively. Histopathologically, the papillary pattern consisted of multiple, thin, delicate filiform, finger-like papillary projections with fibrovascular cores. Besides, the exophytic pattern consisted of the broad-based bulbous to "cauliflower-like" exophytic growth with rounded projections. Immunohistochemically, positivity for CKpan, CKhmw (high molecular weight), and p53, yet negativity for CK8, vimentin, desmin, smooth muscle actin, and S-100 was observed in PSCC. In conclusion, 2 specific histopathologic growth patterns of oral PSCC were identified to separate from conventional SCC. Patients with PSCC have a favorable outcome in relation to exophytic nature and limited invasion of the tumor. PMID- 22672807 TI - Community hospital admission from the emergency department by persons with substance use disorders. AB - Persons with a substance use disorder (SUD) are less likely to be insured and may have limited access to appropriate care, thereby increasing their reliance on emergency departments (EDs). We investigated whether health conditions and insurance status are significant predictors of admission to a community hospital directly from an ED visit with an SUD diagnosis. We analyzed the 2008 Nationwide Emergency Department Sample of the Healthcare Cost and Utilization Project. Lack of health insurance was disproportionately likely in ED visits that carried an SUD diagnosis, whether alcohol- or drug-related. Using regression analysis, most SUD and non-SUD diagnostic categories and many procedure categories were significantly related to subsequent hospital admission. Controlling for clinical characteristics, SUD-related ED visits covered by public or private insurance had substantially higher odds of leading to hospital admission than did uninsured visits. Policies that broaden insurance coverage may improve access to inpatient care for persons with SUDs. PMID- 22672808 TI - Proposing indicators to measure achievement and shortfall inequality consistently. AB - In several economic fields, such as those related to health or education, the individuals' characteristics are measured by bounded variables. Accordingly, these characteristics may be indistinctly represented by achievements or shortfalls. A difficulty arises when inequality needs to be assessed. One may focus either on achievements or on shortfalls but the respective inequality rankings may lead to contradictory results. In this note we propose a procedure to define indicators that measure equally the achievement and shortfall inequality. Specifically, we derive measures which are invariant under ratio scale or translation transformations, and a decomposable measure is also obtained. As the indicators proposed depend on the distribution bounds, families of indices that guarantee the same inequality rankings regardless of the distribution maximal levels are identified. PMID- 22672810 TI - Comments to "Multicorrelation models and uptake factors to estimate extractable metal concentrations from soil and metal in plants in pasturelands fertilized with manure" by Lopes et al. (2012). [Environmental Pollution 166 (2012) 17-22]. PMID- 22672811 TI - Ozone, climate change and forests. PMID- 22672814 TI - Stochastic simulations of a synthetic bacteria-yeast ecosystem. AB - BACKGROUND: The field of synthetic biology has greatly evolved and numerous functions can now be implemented by artificially engineered cells carrying the appropriate genetic information. However, in order for the cells to robustly perform complex or multiple tasks, co-operation between them may be necessary. Therefore, various synthetic biological systems whose functionality requires cell cell communication are being designed. These systems, microbial consortia, are composed of engineered cells and exhibit a wide range of behaviors. These include yeast cells whose growth is dependent on one another, or bacteria that kill or rescue each other, synchronize, behave as predator-prey ecosystems or invade cancer cells. RESULTS: In this paper, we study a synthetic ecosystem comprising of bacteria and yeast that communicate with and benefit from each other using small diffusible molecules. We explore the behavior of this heterogeneous microbial consortium, composed of Saccharomyces cerevisiae and Escherichia coli cells, using stochastic modeling. The stochastic model captures the relevant intra-cellular and inter-cellular interactions taking place in and between the eukaryotic and prokaryotic cells. Integration of well-characterized molecular regulatory elements into these two microbes allows for communication through quorum sensing. A gene controlling growth in yeast is induced by bacteria via chemical signals and vice versa. Interesting dynamics that are common in natural ecosystems, such as obligatory and facultative mutualism, extinction, commensalism and predator-prey like dynamics are observed. We investigate and report on the conditions under which the two species can successfully communicate and rescue each other. CONCLUSIONS: This study explores the various behaviors exhibited by the cohabitation of engineered yeast and bacterial cells. The way that the model is built allows for studying the dynamics of any system consisting of two species communicating with one another via chemical signals. Therefore, key information acquired by our model may potentially drive the experimental design of various synthetic heterogeneous ecosystems. PMID- 22672815 TI - Vascular resection and reconstruction at pancreatico-duodenectomy: technical issues. AB - BACKGROUND: With the improvement of perioperative management over the years, pancreatico-duodenectomy has become a safe operation despite its technical complexity. The presence of concomitant visceral artery occlusion unrelated to the underlying malignancy and concomitant major venous infiltration by tumor poses additional hazards to resection which could compromise the postoperative outcome. DATA SOURCES: A MEDLINE database search was performed to identify relevant articles using the key words "median arcuate ligament syndrome", "superior mesenteric artery", "replaced right hepatic artery", and "portal vein resection". Additional papers and book chapters were identified by a manual search of the references from the key articles. RESULTS: Computed tomography with 3-dimensional reconstruction of the vascular anatomy provides most key information on the potential vascular problems encountered during surgery. A trial clamping of the gastroduodenal artery provides a simple intraoperative assessment for the presence of any significant visceral arterial occlusion. Depending on the timing of diagnosis, division of the median arcuate ligament, bypass or endovascular stenting should be considered. Portal and superior mesenteric vein resection had been used with increasing frequency and safety. The steps and methods taken to reconstruct the venous continuity vary with individual surgeons, and the anatomical variations encountered. With segmental loss of the portal vein, opinions differs with regard to the preservation of the splenic vein, and when divided, the necessity of restoring its continuity; source of the autologous vein graft when needed and whether the use of synthetic graft is a safe alternative. CONCLUSIONS: During a pancreatico-duodenectomy, images of computed tomography must be carefully studied to appreciate the changes and variation of vascular anatomy. Adequate preoperative preparation, acute awareness of the probable arterial and venous anatomical variation and the availability of expertise, especially micro-vascular surgery, for vascular reconstruction would help to make the complex pancreatic resection a safer procedure. PMID- 22672816 TI - Key challenges to the development of extracorporeal bioartificial liver support systems. AB - BACKGROUND: For nearly three decades, extracorporeal bioartificial liver (BAL) support systems have been anticipated as promising tools for the treatment of liver failure. However, these systems are still far from clinical application. This review aimed to analyze the key challenges to the development of BALs. DATA SOURCE: We carried out a PubMed search of English-language articles relevant to extracorporeal BAL support systems and liver failure. RESULTS: Extracorporeal BALs face a series of challenges. First, an appropriate cell source for BAL is not readily available. Second, existing bioreactors do not provide in vivo-like oxygenation and bile secretion. Third, emergency needs cannot be met by current BALs. Finally, the effectiveness of BALs, either in animals or in patients, has been difficult to document. CONCLUSIONS: Extracorporeal BAL support systems are mainly challenged by incompetent cell sources and flawed bioreactors. To advance this technology, future research is needed to provide more insights into interpreting the conditions for hepatocyte differentiation and liver microstructure formation. PMID- 22672817 TI - Living donor liver transplantation in 43 children with biliary atresia: a single center experience from the mainland of China. AB - BACKGROUND: There is no large-cohort report on living donor liver transplantation (LDLT) for biliary atresia (BA) patients from the mainland of China. This single center study describes our initial experience with 43 LDLTs for BA patients aged two years or younger. METHODS: In this study, the eligibility criteria were BA as the primary diagnosis and two years of age or younger. From October 2006 to December 2010, the clinical data of 43 LDLTs, including pre-operative evaluations, surgical techniques, postoperative complications and outcomes of donors and recipients, were retrospectively analyzed. RESULTS: Donor graft type was the left lateral segment with compatible ABO blood groups. Forty-three recipients were selected in this study. The median patient age at operation was 9 months (range 6-24), and the median body weight was 8 kg (range 5.7-12.5). Fourteen (32.6%) recipients received Kasai operations before liver transplantation. The overall one- and two-year cumulative survival rates for grafts and recipients were 81%, 81% and 76%, 76%, respectively. No donor mortality was encountered, with a minimal morbidity and no long-term sequelae. Nine out of 43 recipients died. Postoperative complications of recipients were biliary leakage and refluxing cholangitis (11/43, 25.6%), hepatic artery thrombosis (4, 9.3%), pulmonary infections (4, 9.3%), portal vein thrombosis (3, 7.0%), wound disruption (3, 7.0%), acute rejection (3, 7.0%), cytomegalovirus infection (2, 4.7%), and intra-abdominal bleeding (1, 2.3%). CONCLUSION: Despite the relatively low survival rates due to lack of experience initially, LDLT still provides encouraging outcomes for pediatric recipients with BA, even small children under two years old. PMID- 22672818 TI - AFP level and histologic differentiation predict the survival of patients with liver transplantation for hepatocellular carcinoma. AB - BACKGROUND: In liver transplantation or resection for hepatocellular carcinoma (HCC), patient selection depends on morphological features. In patients with HCC, we performed a clinicopathological analysis of risk factors that affected survival after liver transplantation. METHODS: In 389 liver transplantations performed from 2004 to 2010, 102 were for HCC patients. Data were collected retrospectively from the Organ Transplantation Center Database. Variables were as follows: age, gender, preoperative alpha-fetoprotein (AFP) levels, Child-Pugh and MELD scores, prognostic staging criteria (Milan and UCSF), etiology, number of tumors, the largest tumor size, total tumor size, multifocality, intrahepatic portal vein tumor thrombosis, bilobarity, and histological differentiation. RESULTS: One hundred and two patients were evaluated. The 5-year overall survival rate was 56.5%. According to the UCSF criteria, 63% of the patients were within and 37% were beyond UCSF (P=0.03). Ten patients were excluded (one with fibrolamellary HCC and 9 because of early postoperative death without HCC recurrence), and 92 patients were assessed. The mean age of the patients was 56.5+/-6.9 years. Sixty-two patients underwent living donor liver transplantations. The mean follow-up time was 29.4+/-22.6 months. Fifteen patients (16.3%) died in the follow-up period due to HCC recurrence. Univariate analysis showed that AFP level, intrahepatic portal vein tumor thrombosis, histologic differentiation and UCSF criteria were significant factors related to survival and tumor recurrence.The 5-year estimated overall survival rate was 62.2% in all patients. According to the UCSF criteria, and the 5-year overall survival rate was 66.7% within and 52.7% beyond the criteria (P=0.04). Multivariate analysis showed that AFP level and poor differentiation were independent factors. CONCLUSIONS: For proper patient selection in liver transplantation for HCC, prognostic criteria related to tumor biology (especially AFP level and histological differentiation) should be considered. Poor differentiation and higher AFP levels are indicators of poor prognosis after liver transplantation. PMID- 22672819 TI - Health-related quality of life after liver transplantation: the experience from a single Chinese center. AB - BACKGROUND: Few studies have been performed to assess health-related quality of life (HRQOL) in liver transplantation (LT) patients in the mainland of China. This study aimed to investigate the HRQOL of post-LT patients in a single center. METHODS: HRQOL was evaluated by the SF-36 (Chinese version) questionnaire in 60 patients (LT group) who had received LT for benign end-stage liver disease (BELD). Fifty-five patients with BELD (BELD group) and 50 healthy volunteers from the general population (GP group) were also evaluated, and the results were compared among the three groups. RESULTS: There was a significant difference among the three groups in terms of the scores of eight domains in the SF-36 (P<0.01). Patients in the BELD group had lower scores in each domain of the SF-36 in comparison with those in the GP group (P<0.025). The LT group had mental health scores equivalent to those of the BELD group (P>0.025), but higher scores for the remaining seven domains (P<0.025). Compared with the GP group, the LT group scored equivalently for role physical, body pain, vitality, social function and role emotion (P>0.025), but had lower scores for the remaining three domains (P<0.025). Lower family income was found to be associated with reduced physical function and mental health scores (P<0.05). Better education was associated with increased mental health scores (P<0.05). CONCLUSIONS: LT patients generally have a good HRQOL although some respects of their HRQOL remains to be improved. Lower family income and poor education are important factors relating to the poor HRQOL of LT patients. PMID- 22672820 TI - Rapid measurement of indocyanine green retention by pulse spectrophotometry: a validation study in 70 patients with Child-Pugh A cirrhosis before hepatectomy for hepatocellular carcinoma. AB - BACKGROUND: The indocyanine green (ICG) retention test is the most popular liver function test for selecting patients for major hepatectomy. Traditionally, it is done using spectrophotometry with serial blood sampling. The newly-developed pulse spectrophotometry is a faster alternative, but its accuracy on Child-Pugh A cirrhotic patients undergoing hepatectomy for hepatocellular carcinoma has not been well documented. This study aimed to assess the accuracy of the LiMON((r)), one of the pulse spectrophotometry systems, in measuring preoperative ICG retention in these patients and to devise an easy formula for conversion of the results so that they can be compared with classical literature records where ICG retention was measured by the traditional method. METHODS: We measured the liver function of 70 Child-Pugh A cirrhotic patients before hepatectomy for hepatocellular carcinoma from September 2008 to January 2009. ICG retention at 15 minutes measured by traditional spectrophotometry (ICGR15) was compared with ICG retention at 15 minutes measured by the LiMON (ICGR15(L)). RESULTS: The median ICGR15 was 14.7% (5.6%-32%) and the median ICGR15(L) was 10.4% (1.2%-28%). The mean difference between them was -4.3606. There was a strong correlation between ICGR15 and ICGR15(L) (correlation coefficient, 0.844; 95% confidence interval, 0.762-0.899). The following formula was devised: ICGR15=1.16XICGR15(L)+2.73. CONCLUSIONS: The LiMON provides a fast and repeatable way to measure ICG retention at 15 minutes, but with constant underestimation of the real value. Therefore, when comparing results obtained by traditional spectrophotometry and the LiMON, adjustment of results from the latter is necessary, and this can be done with a simple mathematical calculation using the above formula. PMID- 22672821 TI - Novel functional proteins interact with midkine in hepatic cancer cells. AB - BACKGROUND: Midkine is a heparin-binding growth factor that promotes the proliferation, survival, migration and differentiation of various target cells. Midkine plays an important role in tumorigenesis and tumor progression, and is overexpressed in many human malignant tumors. Patients with high tumor midkine expression frequently have a worse prognosis than those with low expression. The present study was designed to investigate the interaction network of midkine in hepatic cancer cells, and to elucidate its role in hepatocellular carcinoma. METHODS: DNA encoding full-length midkine was cloned into pDBLeu vector to serve as bait in yeast two-hybrid screening to identify interacting proteins. Candidate proteins were examined on SC-Leu-Trp-His+3-AT (20 mmol/L) plates and assayed for X-gal activity, then sequenced and classified according to the GenBank. Finally, identified proteins were expressed by the in vitro expression system pCMVTnT, and protein interactions were confirmed by co-immunoprecipitation. RESULTS: Using the yeast two-hybrid system, we found 6 proteins that interacted with midkine: NK kappa-B inhibitor alpha (I-kappa-B-alpha), Dvl-binding protein naked cuticle 2, granulin, latent active TGF-beta binding protein 3, latent active TGF-beta binding protein 4, and phospholipid scramblase 1. In vitro co-immunoprecipitation demonstrated that all identified proteins directly interacted with midkine. CONCLUSION: The identification of midkine-interacting proteins in hepatic cancer cells indicates that midkine is a multifunctional factor that may participate in cell migration, differentiation, and proliferation, and is also associated with the multicellular response feedback during the development of hepatocellular carcinoma. PMID- 22672822 TI - Inhibition of GSK-3beta ameliorates hepatic ischemia-reperfusion injury through GSK-3beta/beta-catenin signaling pathway in mice. AB - BACKGROUND: Glycogen synthase kinase (GSK)-3beta/beta-catenin signaling regulates ischemia-reperfusion (I/R)-induced apoptosis and proliferation, and inhibition of GSK-3beta has beneficial effects on I/R injury in the heart and the central nervous system. However, the role of this signaling in hepatic I/R injury remains unclear. The present study aimed to investigate the effects and mechanism of GSK 3beta/beta-catenin signaling in hepatic I/R injury. METHODS: Male C57BL/6 mice (weighing 22-25 g) were pretreated with either SB216763, an inhibitor of GSK 3beta, or vehicle. These mice were subjected to partial hepatic I/R. Blood was collected for test of alanine aminotransferase (ALT), and liver specimen for assays of phosphorylation at the Ser9 residue of GSK-3beta, GSK-3beta activity, axin 2 and the anti-apoptotic factors Bcl-2 and survivin, as well as the proliferative factors cyclin D1 and proliferating cell nuclear antigen, and apoptotic index (TUNEL). Real-time PCR, Western blotting and immunohistochemical staining were used. RESULTS: SB216763 increased phospho-GSK-3beta levels and suppressed GSK-3beta activity (1880+/-229 vs 3280+/-272 cpm, P<0.01). ALT peaked at 6 hours after reperfusion. Compared with control, SB216763 decreased ALT after 6 hours of reperfusion (4451+/-424 vs 7868+/-845 IU/L, P<0.01), and alleviated hepatocyte necrosis and vacuolization. GSK-3beta inhibition led to the accumulation of beta-catenin in the cytosol (0.40+/-0.05 vs 1.31+/-0.11, P<0.05) and nucleus (0.62+/-0.14 vs 1.73+/-0.12, P<0.05), beta-catenin further upregulated the expression of axin 2. Upregulation of GSK-3beta/beta-catenin signaling increased Bcl-2, survivin and cyclin D1. Serological and histological analyses showed that SB216763 alleviated hepatic I/R-induced injury by reducing apoptosis (1.4+/-0.2% vs 3.6+/-0.4%, P<0.05) and enhanced liver proliferation (56+/-8% vs 19+/-4%, P<0.05). CONCLUSION: Inhibition of GSK-3beta ameliorates hepatic I/R injury through the GSK-3beta/beta-catenin signaling pathway. PMID- 22672823 TI - Functional distinction of rat liver natural killer cells from spleen natural killer cells under normal and acidic conditions in vitro. AB - BACKGROUND: The microenvironment within solid tumors has often been shown to exhibit an acidic extracellular pH. Although the morphologic and functional differences in natural killer (NK) cells of the liver and spleen have been reported previously under physiological conditions, the difference under acidic conditions is still unclear. This study was to investigate the differences in the morphological and functional characteristics between rat liver and spleen NK cells under normal and acidic conditions in vitro. METHODS: Liver and spleen NK cells were isolated and purified from Sprague-Dawley rats by density gradient centrifugation and the Dynabeads((r)) FlowComp(TM) Flexi system, and stimulated for 4 days with or without IL-2 or treated with low pH or control for different times. Morphology was examined by scanning electron microscopy (SEM) and transmission electron microscopy (TEM), cell death and proliferation assays were performed by flow cytometry, IFN-gamma production was tested by ELISA, and cytotoxic activity was evaluated by lactate dehydrogenase (LDH) release assay. RESULTS: Liver NK cells had significantly higher levels of cytotoxic activity than spleen NK cells under normal and acidic conditions, and the maximum difference was observed at pH 5.6. Further analysis revealed that the cytotoxic activity of NK cells was correlated with morphology, cell death, proliferative activity and IFN-gamma production. By TEM, liver NK cells contained a greater number of electron-dense granules per cell at pH 5.6. Moreover, a modest elevation of cell death and reduction of proliferation of liver NK cells occurred within a range of 5.6-7.2. Interestingly, an acidic extracellular pH only marginally, and not significantly, suppressed IFN-gamma production by liver NK cells. CONCLUSION: The sharp morphological and functional differences shown by the two types of NK cells in vitro indicate that liver NK cells are unexpectedly resistant to pH shock. PMID- 22672824 TI - Effect of recombinant human growth hormone and interferon gamma on hepatic collagen synthesis and proliferation of hepatic stellate cells in cirrhotic rats. AB - BACKGROUND: Fibrosis plays a key role in the development of liver cirrhosis. In this study, we investigated the effect of growth hormone and interferon gamma on hepatic collagen synthesis and the proliferation of hepatic stellate cells in a cirrhotic rat model. METHODS: Cirrhosis was induced in rats using carbon tetrachloride. Rats were simultaneously treated with daily subcutaneous injections of recombinant human growth hormone or interferon gamma combined with recombinant human growth hormone. The control group was given saline. The relative content of type I and type IV collagen was assessed by indirect immunofluorescence analysis. Activated hepatic stellate cells were prepared from cirrhotic rats. The 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) method was used to assess the effects of recombinant human growth hormone and interferon gamma on these cells in vitro. RESULTS: Both qualitative and quantitative analysis showed that type I and type IV collagen secretion increased with time after recombinant human growth hormone administration and was significantly higher than control and recombinant human growth hormone combined with interferon gamma administration. In vitro, recombinant human growth hormone significantly stimulated hepatic stellate cell proliferation in a concentration dependent manner (10(-3)-10(-1) mg/100 MUL), and interferon gamma (10(-2)-10(-1) MUg/100 MUL) significantly inhibited their growth compared to the control group. Interferon gamma combined with recombinant human growth hormone eliminated this growth-promoting effect to a certain degree in a concentration-dependent manner (10(-1) MUg/100 MUL, P<0.05, 10(-2)-10(-3) MUg/100 MUL, P>0.05) and a time dependent manner (P<0.05). CONCLUSIONS: Recombinant human growth hormone increased collagen secretion in cirrhotic rats in vivo and promoted the proliferation of hepatic stellate cells from cirrhotic rats in vitro. It is possible that concurrent interferon gamma therapy can offset these side-effects of recombinant human growth hormone. PMID- 22672825 TI - Quality control measures for lowering the seroconversion rate of hemodialysis patients with hepatitis B or C virus. AB - BACKGROUND: Hemodialysis (HD) patients are at high risk of infection by hepatitis B virus (HBV) or hepatitis C virus (HCV). The present study was designed to determine the impact of quality control measures on the prevention of transmission of blood-borne viruses. METHODS: A total of 6182 adult maintenance HD patients from all HD units in Zhejiang Province were recruited on January 1, 2007. The baseline demographic and clinical characteristics were recorded and all patients were followed up until death or survival at 4 years later. The Quality Control Standards of Hemodialysis were gradually implemented in HD units. The HBV or HCV seroconversion rates of the recruited patients were calculated and compared every year during the observation period. RESULTS: The prevalence of HBV was 8.3% at the beginning of the study, and 6.6% for HCV. With the implementation of the HD quality control measures, the HBV seroconversion rate tended to decrease year by year (X2=6.620, P=0.085), and the HCV seroconversion rate decreased significantly (X2=10.41, P=0.015). Compared with the data in 2007, the HBV seroconversion rate (X2=4.204, P=0.040, relative risk ratio 0.393, 95% CI 0.156-0.991) and the HCV seroconversion rate (X2=7.373, P=0.007, relative risk ratio 0.386, 95% CI 0.189-0.787) decreased significantly in 2010. CONCLUSION: Quality control measures for HD decreased the seroconversion rates of HBV or HCV in HD patients, showing that updated quality control measures reduce the risk for transmission of blood-borne viruses in the HD population. PMID- 22672826 TI - Can the biliary enhancement of Gd-EOB-DTPA predict the degree of liver function? AB - BACKGROUND: Excretion of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) in the bile may be related to liver function, because of elimination from the liver after preferential uptake by hepatocytes. The purpose of this study was to investigate the relation between liver and biliary enhancement in patients with or without liver dysfunction, and to compare the tumor-to-liver contrast in these patients. METHODS: Forty patients [group 1: normal liver and Child-Pugh class A in 20 patients, group 2: Child-Pugh class B in 18 patients and Child-Pugh C in 2] were evaluated. All patients underwent MR imaging of the liver using a 1.5-Tesla system. T1-weighted 3D images were obtained at 5, 10, 15 and 20 minutes after Gd-EOB-DTPA injection. The relation between group 3 (total bilirubin <1.8 mg/dL) and group 4 (total bilirubin >=1.8 mg/dL) was investigated at 20 minutes. Liver and biliary signals were measured, and compared between groups 1 and 2 or groups 3 and 4. Tumor-to-liver ratio was also evaluated between groups 1 and 2. Scheffe's post-hoc test after two-way repeated-measures ANOVA and Pearson's correlation test were used for statistical analysis. RESULTS: Liver enhancement showed significant difference at all time points between groups 1 and 2. Biliary enhancement did not show a significant difference between groups 1 and 2 at 5 minutes, but did at 10, 15 and 20 minutes. At 20 minutes, significant differences between groups 3 and 4 were seen for liver and biliary enhancement. At all time points, liver enhancement correlated with biliary enhancement in both groups. At 5 minutes and 20 minutes, statistical differences between groups 1 and 2 were seen for tumor-to-liver ratio. CONCLUSIONS: The degree of biliary enhancement has a close correlation to that of liver enhancement. It is especially important that insufficient liver enhancement causes lower tumor-to-liver contrast in the hepatobiliary phase of Gd-EOB-DTPA. PMID- 22672827 TI - Quantitative analysis of intestinal gas in patients with acute pancreatitis. AB - BACKGROUND: Disturbance of gastrointestinal function is a common complication in the early phase of acute pancreatitis (AP). Intestinal gas may reflect the function of the gut. Using plain abdominal radiographs, we investigated whether intestinal gas volume is related to AP. METHODS: Plain abdominal radiographs of 68 patients with AP within 24 hours after admission and 21 normal controls were digitized and transmitted to a computer. The region of intestinal gas was identified by an image manipulation software and the gas volume score (GVS) was calculated. The relationships between the GVS values and various clinical factors of AP were analyzed. RESULTS: The GVS in the AP group was 0.084+/-0.016, in the mild AP (MAP) group 0.070+/-0.005, and in the severe AP (SAP) group 0.094+/ 0.013; all values were higher than that in the control group (P<0.01). The GVS in the SAP group was higher than that in the MAP group. The GVSs were correlated to the Ranson's scores (r=0.762, P<0.01) and the acute physiology and chronic health evaluation II (APACHE II) scores (r=0.801, P<0.01). In addition, the GVS in patients with secondary pancreatic and/or peripancreatic infection was 0.107+/ 0.014, higher than that in patients without secondary infection (P<0.01). GVS was not related to gender, age, etiology or clinical outcome of AP. CONCLUSIONS: Intestinal gas volume is significantly elevated in patients with AP. It is closely related to Ranson's and APACHE II score and secondary pancreatic and/or peripancreatic infection. GVS may be a new prognostic tool for assessing the severity of AP in the early course of the disease. PMID- 22672828 TI - Induction, modulation and potential targets of miR-210 in pancreatic cancer cells. AB - BACKGROUND: MiR-210 is induced by hypoxia and plays different roles in the development of certain cancers. However, little is known about its role in pancreatic cancer (PC). This study aimed to explore the induction and modulation of PC by miR-210 and its potential molecular targets. METHODS: PC cells were cultured under normoxic and hypoxic conditions. Expression of miR-210 and hypoxia inducible factor (HIF)-1alpha was detected using quantitative reverse transcription polymerase chain reaction. Cancer cells were transiently transfected with HIF-1alpha small interfering RNA (siRNA) and miR-210 mimics, and cell proliferation was measured using the CCK-8 assay. Potential targets for miR 210 were then identified using a dual luciferase reporter assay. RESULTS: Hypoxic conditions induced miR-210 expression in six PC cell lines (AsPC-1, BxPC-3, MIAPaCa-2, PANC-1, Su86.86 and SW1990), but not in Capan-1 or T3M4 cells. Transfection of HIF-1alpha siRNA into PANC-1 cells markedly inhibited HIF-1alpha expression, and subsequently down-regulated miR-210 expression under hypoxic conditions. MiR-210 had no observable impact on the proliferation of PANC-1 or Su86.86 cells and dual luciferase reporter assays showed significantly reduced luciferase activity in the wild-type E2F3, EFNA3, GIT2, MNT, ZNF462 and EGR3 constructs, compared to the corresponding mutants, but not in HOXA3. CONCLUSIONS: These results suggest that miR-210 expression in PC cells is induced by hypoxia through a HIF-1alpha-dependent pathway, but does not influence PC cell proliferation. Also, E2F3, EFNA3, GIT2, MNT, ZNF462 and EGR3 may be potential miR 210 targets in PC. PMID- 22672829 TI - Pancreas-preserving segmental duodenectomy for gastrointestinal stromal tumor of the duodenum and splenectomy for splenic angiosarcoma. AB - BACKGROUND: Gastrointestinal stromal tumors are the most common mesenchymal tumors of the gastrointestinal tract and occur rarely in the duodenum. Splenic angiosarcoma is an aggressive neoplasm with an extremely poor prognosis. METHODS: We report a case of a 70-year-old man hospitalized for abdominal pain in the upper quadrants, dyspepsia and nausea, previously treated for Hodgkin lymphoma 30 years ago. Abdominal CT showed a solid nodular lesion in the third portion of the duodenum, the presence of retropancreatic, aortic and caval lymph nodes, and four nodular splenic masses. (111)In-octreotide scintigraphy revealed pathological tissue accumulation in the duodenal region, and in the retropancreatic, retroduodenal, aortic and caval lymph nodes, suggesting a nonfunctioning neuroendocrine peripancreatic tumor. RESULTS: At exploratory laparotomy, an exophytic soft tumor was found originating from the third portion of the duodenum. Pancreas-preserving duodenectomy with duodenojejunostomy, splenectomy and lymphnodectomy of retropancreatic aortic and caval lymph nodes were performed. Pathological evaluation and immunohistochemical studies showed the presence of a duodenal gastrointestinal stromal tumor with low mitotic activity and a well-differentiated angiosarcoma localized to the spleen and invading lymph nodes. CONCLUSIONS: We speculated that the angiosarcoma and duodenal gastrointestinal stromal tumors of this patient were due to the treatment of Hodgkin lymphoma with radiotherapy 30 years ago. Pancreas-preserving segmental duodenectomy can be used to treat non-malignant neoplasms of the duodenum and avoid extensive surgery. Splenectomy is the treatment of choice for localized angiosarcomas but a strict follow-up is mandatory because of the possibility of recurrence. PMID- 22672830 TI - Management of splenic artery aneurysm associated with extrahepatic portal vein obstruction. AB - BACKGROUND: Splenic artery aneurysms although rare are clinically significant in view of their propensity for spontaneous rupture and life-threatening bleeding. While portal hypertension is an important etiological factor, the majority of reported cases are secondary to cirrhosis of the liver. We report three cases of splenic artery aneurysms associated with extrahepatic portal vein obstruction and discuss their management. METHODS: The records of three patients of splenic artery aneurysm associated with extrahepatic portal vein obstruction managed from 2003 to 2010 were reviewed retrospectively. The clinical presentation, surgical treatment and outcome were analyzed. RESULTS: The aneurysm was >3 cm in all patients. The clinical symptoms were secondary to extrahepatic portal vein obstruction (hematemesis in two, portal biliopathy in two) while the aneurysm was asymptomatic. Doppler ultrasound demonstrated aneurysms in all patients. A proximal splenorenal shunt was performed in two patients with excision of the aneurysm in one patient and ligation of the aneurysm in another one. The third patient had the splenic vein replaced by collaterals and hence underwent splenectomy with aneurysmectomy. All patients had an uneventful post-operative course. CONCLUSIONS: Splenic artery aneurysms are associated with extrahepatic portal vein obstruction. Surgery is the mainstay of treatment. Although technically difficult, it can be safely performed in an experienced center with minimal morbidity and good outcome. PMID- 22672832 TI - In vivo tendon engineering with skeletal muscle derived cells in a mouse model. AB - Engineering a functional tendon with strong mechanical property remains an aim to be achieved for its eventual application. Both skeletal muscle and tendon are closely associated during their development and both can bear strong mechanical loading dynamically. This study explored the possibility of engineering stronger tendons with mouse skeletal muscle derived cells (MDCs) and with mouse tenocytes as a control. The results demonstrated that both MDCs and tenocytes shared the gene expression of growth differentiation factor-8 (GDF-8), collagens I, III, VI, scleraxis and tenomodulin, but with MyoD gene expression only in MDCs. Quantitatively, MDCs expressed higher levels of GDF-8, collagens III and VI (p < 0.05), whereas tenocytes expressed higher levels of collagen I, scleraxis and tenomodulin (p < 0.05). Interestingly, MDCs proliferated faster with more cells in S + G2/M phases than tenocytes (p < 0.05). After been seeded on polyglycolic acid (PGA) fibers, MDCs formed better quality engineered tendons with more mature collagen structure and thicker collagen fibrils as opposed to tenocyte engineered tendons. Biochemically, more collagen VI and decorin were produced in the former than in the later. Functionally, MDC engineered tendons exhibited stronger mechanical properties than tenocyte engineered tendons, including maximal load, stiffness, tensile strength and Young's modulus (p < 0.05). Furthermore, with the increase of implantation time, MDCs gradually lost their expression of myogenic molecules of MyoD and desmin and gained the expression of tenomodulin, a marker for tenocytes. Collectively, these results indicate that MDCs may serve as a desirable alternative cell source for engineering functional tendon tissue. PMID- 22672831 TI - Modulation of chondrocyte behavior through tailoring functional synthetic saccharide-peptide hydrogels. AB - Tailoring three-dimensional (3D) biomaterial environments to provide specific cues in order to modulate function of encapsulated cells could potentially eliminate the need for addition of exogenous cues in cartilage tissue engineering. We recently developed saccharide-peptide copolymer hydrogels for cell culture and tissue engineering applications. In this study, we aim to tailor our saccharide-peptide hydrogel for encapsulating and culturing chondrocytes in 3D and examine the effects of changing single amino acid moieties differing in hydrophobicity/hydrophilicity (valine (V), cysteine (C), tyrosine (Y)) on modulation of chondrocyte function. Encapsulated chondrocytes remained viable over 21 days in vitro. Glycosaminoglycan and collagen content was significantly higher in Y-functionalized hydrogels compared to V-functionalized hydrogels. Extensive matrix accumulation and concomitant increase in mechanical properties was evident over time, particularly with the presence of Y amino acid. After 21 days in vitro, Y-functionalized hydrogels attained a modulus of 193 +/- 46 kPa, compared to 44 +/- 21 kPa for V-functionalized hydrogels. Remarkably, mechanical and biochemical properties of chondrocyte-laden hydrogels were modulated by change in a single amino acid moiety. This unique property, combined with the versatility and biocompatibility, makes our saccharide-peptide hydrogels promising candidates for further investigation of combinatorial effects of multiple functional groups on controlling chondrocyte and other cellular function and behavior. PMID- 22672833 TI - Spatial control of cell-mediated degradation to regulate vasculogenesis and angiogenesis in hyaluronan hydrogels. AB - Matrix remodeling is crucial for neovascularization, however its utilization to control this process in synthetic biomaterials has been limited. Here, we utilized hyaluronic acid (HA) hydrogels to spatially control cellular remodeling during vascular network formation. Specifically, we exploited a secondary radical polymerization to alter the ability of cells to degrade the hydrogel and utilized it to create spatial patterning using light initiation. We first demonstrated the ability of the hydrogel to either support or inhibit in vitro vasculogenesis of endothelial colony-forming cells (ECFCs) or angiogenesis from ex ovo chorioallantoic membranes. We showed that vascular tube branching and sprouting, which required matrix metalloproteinases (MMPs)-dependent remodeling, could be achieved in hydrogels formed by primary addition-crosslinking only. Although ECFCs expressed higher levels of MMPs in the hydrogels with the secondary radical crosslinking, the generated kinetic chains disabled cell-mediated remodeling and therefore vascular formation was arrested at the vacuole and lumen stage. We then patterned hydrogels to have regions that either permitted or inhibited cell mediated degradation during in vitro vasculogenesis or angiogenesis. Our ability to control degradation cues that regulate vascular tube formation is important for the study of vascular biology and the application of synthetic biomaterials in tissue regeneration. PMID- 22672834 TI - The effect of differentiation stage of amniotic fluid stem cells on bone regeneration. AB - Bone tissue engineering strategies require cells with high proliferative and osteogenic potential as well as a suitable scaffold to support the development of these as they form new bone tissue. In this study, we evaluated whether the differentiation stage of amniotic fluid stem cells (AFSC) could enhance the regeneration of critical sized femoral defects in a rat model. For this purpose, AFSC were seeded onto a starch-poly(epsilon-caprolactone) (SPCL) scaffold and were cultured in vitro in osteogenic culture media for different periods of time in order to obtain: i) undifferentiated cells, ii) cells committed to the osteogenic phenotype and iii) "osteoblast-like" cells. In vitro results indicate that AFSC were considered to be osteogenically committed by the end of week 2 and osteoblastic-like after week 3 in culture. Constructs composed of AFSC-SPCL scaffolds from each differentiation stage were implanted into critical sized femoral defects. The quality of new tissue formed in the defects was evaluated based on micro-CT imaging and histological analysis of constructs retrieved at 4 and 16 weeks after implantation. In vivo formation of new bone was observed under all conditions. However, the most complete repair of the defect was observed after 16 weeks in the animals receiving the SPCL scaffolds seeded with osteogenically committed AFSC. Furthermore, the presence of blood vessels was noted in the inner sections of the scaffolds suggests that these cells could potentially be used to induce bone regeneration and angiogenesis in non-union bone defects. PMID- 22672835 TI - The gene transfection properties of a lipophosphoramidate derivative with two phytanyl chains. AB - Development of efficient and non-toxic gene delivery systems is among the most challenging requirements for successful gene therapy. Cationic lipophosphoramidates constitute a class of cationic lipids we have already shown to be efficient for in vivo gene transfer. Herein, we report the synthesis of a cationic lipophosphoramidate bearing two phytanyl chains (BSV18) as hydrophobic domain, and studied its gene transfection properties. In vitro, BSV18 exhibited a high transfection efficacy associated with a low cytotoxicity. (31)P NMR studies of various cationic lipophosphoramidates in water solution suggested that the phytanyl chains may favor the formation of an inverted hexagonal phase, a supramolecular arrangement which is presumed to enhance the endosomal escape and consequently increase the transfection efficiency. In vivo, systemic delivery of BSV18-based lipoplexes allowed a high efficiency of gene transfection into the mouse lung. With a view to clinical application, we evaluated not only the efficiency of lung transfection but also the eventual in vivo side-effects. Thus, in addition to monitoring the in vivo transfection efficiency by bioluminescent imaging and identifying by immunohistochemistry the cell types transfected, we also assessed in living animals the potential liver reaction as well as the inflammatory and immune responses induced by BSV18-mediated transfection. All those adverse effects were actually highly transient. Thus, taken together, these results indicate that lipophosphoramidates equipped with two phytanyl chains may have great potential for lung gene therapy, in particular for Cystic Fibrosis. PMID- 22672836 TI - Cancer cell labeling and tracking using fluorescent and magnetic nanodiamond. AB - Nanodiamond, a promising carbon nanomaterial, develops for biomedical applications such as cancer cell labeling and detection. Here, we establish the nanodiamond-bearing cancer cell lines using the fluorescent and magnetic nanodiamond (FMND). Treatment with FMND particles did not significantly induce cytotoxicity and growth inhibition in HFL-1 normal lung fibroblasts and A549 lung cancer cells. The fluorescence intensities and particle complexities were increased in a time- and concentration-dependent manner by treatment with FMND particles in lung cancer cells; however, the existence of FMND particles inside the cells did not alter cellular size distribution. The FMND-bearing lung cancer cells could be separated by the fluorescent and magnetic properties of FMNDs using the flow cytometer and magnetic device, respectively. The FMND-bearing cancer cells were identified by the existence of FMNDs using flow cytometer and confocal microscope analysis. More importantly, the cell morphology, viability, growth ability and total protein expression profiles in the FMND-bearing cells were similar to those of the parental cells. The separated FMND-bearing cells with various generations were cryopreservation for further applications. After re thawing the FMND-bearing cancer cell lines, the cells still retained the cell survival and growth ability. Additionally, a variety of human cancer types including colon (RKO), breast (MCF-7), cervical (HeLa), and bladder (BFTC905) cancer cells could be used the same strategy to prepare the FMND-bearing cancer cells. These results show that the FMND-bearing cancer cell lines, which reserve the parental cell functions, can be applied for specific cancer cell labeling and tracking. PMID- 22672837 TI - Detection and visualization of intracutaneous allergic type-specific elements using long-wavelength near-infrared hyperspectral imaging. AB - BACKGROUND/PURPOSE: This study aimed to develop a method for the assessment of allergic dermatitis by using the long-wavelength near-infrared spectrum (more than 1000 nm) to detect intracutaneous allergic type-specific elements. Such a method was realized by establishing a spectral classifier for the spectra of type I and type IV allergic dermatitis reactions. METHODS: Near-infrared spectral images of histamine-induced cutaneous reaction (type I) and contact hypersensitivity erythema elicited by squaric acid dibutylester (SADBE; type IV) were obtained, and the absorption spectra of normal and inflamed skin were extracted from these spectral images. A spectral classifier was established from these training datasets, and it was then applied to two test cases, red flare by methyl nicotinate (normal) and metal allergy (type IV). RESULTS: The spectral classifier established by canonical discriminant analysis (CDA) achieved very accurate detection (normal: 87.67%, type I: 87.00%, type IV: 98.5%). Furthermore, the test cases were also correctly classified: the red flare induced by methyl nicotinate was categorized as normal skin and the metal allergy was categorized as a type IV allergic reaction. CONCLUSIONS: These results suggest a possible application of near-infrared spectral imaging to the assessment of allergic dermatitis. PMID- 22672839 TI - A case of ambiguous external genitalia in a Thoroughbred male horse with the 63,XO/64,XY mosaic karyotype. AB - A Thoroughbred colt with ambiguous external genitalia was presented for clinical and histological examinations. The colt had a short penis that faced backward between his hind limbs. The measurements of luteinizing hormone, follicle stimulating hormone, testosterone and ir-inhibin showed a tendency to increase gradually from April. Both the sex-determining region of the Y chromosome and amelogenin gene fragments were detected by the PCR method. A cytogenetic analysis revealed the 63,XO/64,XY mosaic karyotype (ratio 83:17). In autopsy, immature symmetrical subcutaneous testes were found in the inguinal regions. The testes and other accessory sex organs were histologically normal. These results add to our knowledge of chromosomal abnormality and information concerning disorders of sex development in the horse. PMID- 22672840 TI - Sensitive detection of whole-genome differentiation among closely-related species of the genus Fusarium using DNA-DNA hybridization and a microplate technique. AB - We developed a new system for detection of whole-genome differentiation using DNA DNA hybridization, and tested its sensitivity with three closely-related Fusarium species. We compared DNA-DNA relatedness to nucleotide sequence homologies of five genetic regions between each of five strains of three Fusarium species. DNA DNA relatedness by our system was 16.2-86.6%. Sequence homologies of 18S rDNA, rDNA cluster region from ITS1 to 28S rDNA, beta-tub, EF-1alpha and lys2 were 100.0, 99.0-100.0, 96.7-100.0, 95.1-99.4, and 94.7-100.0%, respectively. Our system could clearly detect differentiation between closely-related fungal species which have very similar morphological-characteristics, and exhibit little diagnoses in nucleotide sequences. Our results suggest that this system is a good tool for identification and phylogenetic analysis of closely-related fungal species. PMID- 22672838 TI - Promoter hypermethylation-induced transcriptional down-regulation of the gene MYCT1 in laryngeal squamous cell carcinoma. AB - BACKGROUND: MYCT1, previously named MTLC, is a novel candidate tumor suppressor gene. MYCT1 was cloned from laryngeal squamous cell cancer (LSCC) and has been found to be down-regulated in LSCC; however, the regulatory details have not been fully elucidated. METHODS: Here, we sought to investigate the methylation status of the CpG islands of MYCT1 and mRNA levels by bisulfite-specific PCR (BSP) based on sequencing restriction enzyme digestion, reverse transcription and real-time quantitative polymerase chain reaction (RQ-PCR). The function of specific sites in the proximal promoter of MYCT1 in LSCC was measured by transient transfection, luciferase assays, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation assay (ChIP). RESULTS: The results suggested hypermethylation of 12 CpG sites of the promoter in both laryngeal cancer tissues and the laryngeal cancer line Hep-2 cell. The hypermethylation of the site CGCG (-695 to 692), which has been identified as the c-Myc binding site, was identified in laryngeal cancer tissues (59/73) compared to paired mucosa (13/73); in addition, statistical analysis revealed that the methylation status of this site significantly correlated with cancer cell differentiation(p < 0.01). The mRNA level of MYCT1 increased in Hep-2 cells treated with 5-aza-C (p < 0.01). The luciferase activity from mutant transfectants pGL3-MYCT1m (-852/+12, mut-695-C > A, mut-693-C > G) was significantly reduced compared with the wild type pGL3 MYCT1 (-852/+12), while the luciferase activity from wild transfectants pGL3 MYCT1 (-852/+12) rose after 5-aza treatment in Hep-2 cells. Finally, EMSA and ChIP confirmed that the methylation of the CGCG (-695 to -692) site prevented c Myc from binding of the site and demethylation treatment of the 5' flanking region of MYCT1 by 5-aza induced the increased occupation of the core promoter by c-Myc (p < 0.01). CONCLUSION: In summary, this study concluded that hypermethylation contributed to the transcriptional down-regulation of MYCT1 and could inhibit cancer cell differentiation in LSCC. DNA methylation of the CGCG site (-695 to -692) of MYCT1 altered the promoter activity by interfering with its binding to c-Myc in LSCC. Epigenetic therapy of reactivating MYCT1 by 5-aza should be further evaluated in clinical trails of LSCC. PMID- 22672841 TI - Feline epidermal nevi resembling human inflammatory linear verrucous epidermal nevus. AB - Multiple, pigmented, verrucous, cutaneous lesions in a 2-year-old female cat were pathologically examined. The lesions were linearly arranged on the right side of the body, and had developed along with moderate pruritus since infancy. Histologically, prominent exophytic, papillomatous outgrowths of the epidermis and acanthosis with intense ortho and parakeratotic hyperkeratosis were characteristic of the lesions. Dermal inflammation with mononuclear cells, neutrophils, and eosinophils was also noted. Inclusion bodies, cellular degeneration, and intranuclear viral particles suggesting papillomavirus infection in the keratinocytes were not observed. Papillomavirus antigen and DNA were not detected in the lesions by immunohistochemistry and polymerase chain reaction, respectively. In accordance with these clinical and histopathological features, the cutaneous lesions of the present cat were diagnosed as epidermal nevi, which were consistent with human inflammatory linear verrucous epidermal nevi. PMID- 22672842 TI - Molecular epidemiological survey of the Babesia gibsoni cytochrome b gene in western Japan. AB - In this study, we conducted a survey of the cytochrome b (cytb) gene of Babesia gibsoni (B. gibsoni) isolated from clinical cases to determine the prevalence of potential atovaquone (ATV)-resistant variants. Ninety-two blood samples were collected from naturally B. gibsoni infected dogs. The cytb nucleotide sequence was determined by direct sequencing. Twelve non-synonymous amino acid substitutions were identified in cytb. The principal ATV-resistant substitution, M121I, was detected in three cases. This survey determined that potentially ATV resistant B. gibsoni strains are present in dogs in Japan. PMID- 22672843 TI - Accumulation of metals in the liver and kidneys of cattle from agricultural areas in Lusaka, Zambia. AB - Intensive agricultural practices are recognized as significant sources of metal pollution in soils and pasture. This study investigated metal contamination in cattle offal from an agricultural area in Zambia, where inorganic fertilizers, agricultural lime, and pesticides are routinely applied. The highest median values (mg/kg, wet weight) of Cu (40.9), Zn (35.2), Cr (1.35) and Ni (0.594) were recorded in the liver, whereas the highest median values of Pb (0.061) and Cd (0.049) were found in kidneys. Maximum levels of Hg, As and Co were under 0.2 mg/kg in both organs. Pb and Cd did not exceed the benchmark values in cattle offal for human consumption and did not pose immediate health risks. Concentrations of Ni and Cr could present a public health concern. Monitoring of metal accumulations in offal of cattle, not only from well-known polluted environments but also agricultural areas, should be done regularly for the health of human consumers. PMID- 22672844 TI - Microfabrication and optical properties of highly ordered silver nanostructures. AB - Using thermal evaporation, we fabricated five uniform and regular arrays of Ag nanostructures with different shapes that were based on an anodized aluminum oxide template and analyzed their optical properties. Round-top-shaped structures are obtained readily, whereas to obtain needle-on-round-top-shaped and needle shaped structures, control of the directionality of evaporation, pore size, length, temperature of the substrate, etc., was required. We then observed optical sensitivity of the nanostructures by using surface-enhanced Raman scattering, and we preliminarily investigated the dependency of Raman signal to the roughness and shape of the nanostructures. PMID- 22672845 TI - Quantitative analysis of the opioid peptide DAMGO in rat plasma and microdialysis samples using liquid chromatography-tandem mass spectrometry. AB - A liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI MS/MS) method for the quantification of the opioid peptide DAMGO in rat plasma, as well as DAMGO and the microdialysis recovery calibrator [(13)C(2),(15)N]-DAMGO in microdialysis samples, is described. The microdialysis samples consisted of 15 MUL Ringer solution containing 0.5% bovine serum albumin. Pretreatment of the samples involved protein precipitation with acetonitrile followed by dilution with 0.01% formic acid. The lower limits of quantification were 0.52 ng/mL and 0.24 ng/mL for DAMGO and [(13)C(2),(15)N]-DAMGO respectively and the response was linear up to 5000 fold higher concentrations. The plasma samples (50 MUL) were precipitated with acetonitrile containing the isotope labeled analog [(13)C(2),(15)N]-DAMGO as internal standard. The method was linear in the range of 11-110,000 ng/mL. The separations were conducted on a HyPurity C18 column, 50*4.6 mm, 3 MUm particle size, with a mobile phase consisting of acetonitrile, water and formic acid to the proportions of 17.5:82.5:0.01. Low energy collision dissociation tandem mass spectrometric (CID-MS/MS) analysis was carried out in the positive ion mode using multiple reaction monitoring (MRM) of the following mass transitions: m/z 514.2->453.2 for DAMGO and m/z 517.2->456.2 for [(13)C(2),(15)N]-DAMGO. The intra-day precision and accuracy did not exceed 5.2% and 93-104% for both compounds and sample types described. The inter-day precision an accuracy were <6.8% and 95-105% respectively. The method described is simple, reproducible and suitable for the analysis of small sample volumes at low concentrations. PMID- 22672846 TI - Similarity analyses of chromatographic fingerprints as tools for identification and quality control of green tea. AB - Similarity assessment of complex chromatographic profiles of herbal medicinal products is important as a potential tool for their identification. Mathematical similarity parameters have the advantage to be more reliable than visual similarity evaluations of often subtle differences between the fingerprint profiles. In this paper, different similarity analysis (SA) parameters are applied on green-tea chromatographic fingerprint profiles in order to test their ability to identify (dis)similar tea samples. These parameters are either based on correlation or distance measurements. They are visualised in colour maps and evaluation plots. Correlation (r) and congruence (c) coefficients are shown to provide the same information about the similarity of samples. The standardised Euclidean distance (ds) reveals less information than the Euclidean distance (de), while Mahalanobis distances (dm) are unsuitable for the similarity assessment of chromatographic fingerprints. The adapted similarity score (ss*) combines the advantages of r (or c) and de. Similarity analysis based on correlation is useful if concentration differences between samples are not important, whereas SA based on distances also detects concentration differences well. The evaluation plots including statistical confidence limits for the plotted parameter are found suitable for the evaluation of new suspected samples during quality assurance. The ss* colour maps and evaluation plots are found to be the best tools (in comparison to the other studied parameters) for the distinction between deviating and genuine fingerprints. For all studied data sets it is confirmed that adequate data pre-treatment, such as aligning the chromatograms, prior to the similarity assessment, is essential. Furthermore, green-tea samples chromatographed on two dissimilar High-Performance Liquid Chromatography (HPLC) columns provided the same similarity assessment. Combining these complementary fingerprints did not improve the similarity analysis of the studied data set. PMID- 22672847 TI - Comparison of GC/MS and LC/MS methods for the analysis of propofol and its metabolites in urine. AB - Gas chromatography-mass spectrometry (GC/MS) and liquid chromatography-mass spectrometry (LC/MS) were compared for their capacity to metabolite identification, sensitivity, and speed of analysis for propofol and its metabolites in urine samples. Acidic hydrolysis, liquid-liquid extraction (LLE), and trimethylsilyl (TMS) derivatization procedures were applied for GC/MS analysis. The LC/MS analysis used a simple sample pretreatment based on centrifugation and dilution. Propofol and four metabolites were successfully analyzed by GC/MS following TMS derivatization. One compound, di isopropanolphenol was tentatively characterized as a new metabolite observed for the first time in human urine. The TMS derivatization greatly improved the chromatographic properties and detection sensitivity, especially for hydroxylated metabolites. The lower limits of quantitation (LLOQ) of propofol were about 325 and 0.51 ng/mL for the GC/MS scan mode and selected ion monitoring (SIM) mode, respectively. In addition, five conjugated propofol metabolites were successfully analyzed by LC-MS/MS in negative ion mode. The detection sensitivity for these conjugated metabolites could be greatly enhanced by the addition of triethylamine to the mobile phase without any loss of LC resolution capacity. The LLOQs of propofol-glucuronide (PG) were about 1.17 and 2.01 ng/mL for the LC-MS-selected ion monitoring (SIM) and multiple reaction monitoring (MRM) mode, respectively. Both GC/MS and LC/MS methods sensitively detected nine metabolites of propofol and could be used to provide complementary data for the reasonable propofol metabolism study. Urinary excretion profiles for propofol and its metabolites following administration to human were suggested based on the total ion chromatograms obtained by GC/MS and LC/MS methods, respectively. PMID- 22672848 TI - Intrahepatic and systemic therapy with oxaliplatin combined with capecitabine in patients with hepatic metastases from breast cancer. AB - BACKGROUND: The aim was to evaluate activity and toxicity of hepatic arterial infusion of oxaliplatin in combination with capecitabine in patients with metastatic breast cancer with liver metastases and limited extrahepatic disease. PATIENTS AND METHODS: Sixteen consecutive patients received capecitabine 13 00mg/m(2) daily combined with oxaliplatin 85 mg/m(2) every two weeks. Seven patients alternated between intrahepatic and systemic oxaliplatin, and in 9 oxaliplatin was primarily given intrahepatic. Five patients had liver-only metastases and 11 had additionally bone metastases. The patients had received median two previous chemotherapeutic regimens for metastatic disease. RESULTS: The response rate was 50% and the stable disease (>=6 months) rate 44%. Median progression free and overall survival was 7.9 and 19.2 months, respectively. The toxicity was moderate with abdominal pain, neuropathy, and hand foot syndrome as the most common adverse events. CONCLUSION: The combination of capecitabine and intrahepatic/systemic therapy with oxaliplatin was active in pretreated patients with liver metastasis from breast cancer. PMID- 22672849 TI - Pregnancy and delivery in patients with Fontan circulation: a report of two cases. AB - Fontan operation is performed to provide palliation for patients with many forms of highly complex congenital heart disease that cannot support a biventricular circulation. Increasing numbers of women who have undergone these connections in childhood are now reaching their childbearing years, and some are becoming pregnant. The low flow and fixed cardiac output of a Fontan circulation poses a number of problems during pregnancy. Here, we report two cases of pregnancy and delivery with Fontan circulation. Case 1, who underwent Fontan procedure for congenital pulmonary atresia with intact vertical septum at age 7, delivered a male infant weighing 1073 g by cesarean section at 28(6/7) weeks due to massive genital bleeding. Case 2 underwent Fontan procedure for double inlet left ventricle and delivered by vacuum extraction a male infant weighing 2142 g, while monitoring central venous pressure at 37(5/7) weeks. The former had ascites and dose of diuretic had to be added at early pregnancy, and the latter had no adverse cardiac and obstetric events. These cases suggest that patients after adequate Fontan palliation could complete pregnancy without long-term cardiac sequelae, but might be complicated with cardiac or obstetrical events. Intensive care should be required with specialists, including a neonatologist, anesthesiologist and cardiologist. We have added a literature review of pregnancy with Fontan circulation, referring to previous reports. PMID- 22672850 TI - [Intrahospital mortality in patients with Clostridium difficile-associated diarrhea infection]. AB - BACKGROUND: Clostridium difficile (C. difficile) is a gram-positive anaerobic bacillus capable of producing diarrhea or colitis in the hospitalized patient, particularly in those exposed to the use of antibiotics, and 6% to 38% mortality in patients with C. difficile-associated diarrhea (CDAD) has been described. AIMS: To determine the hospital death rate in patients presenting with CDAD. As a secondary aim, hospital stay and risk factors for unfavorable outcome were recorded. METHODS: A retrospective cohort study was carried out. The case records of hospitalized patients presenting with diarrhea and that tested positive for C. difficile through toxin A and B assays were reviewed. The number of non-surviving patients that presented with CDAD during hospitalization was recorded along with the principal factors associated with the worst outcome. RESULTS: Of the 66 patients enrolled in the study, 6 (9,1%) died during their hospitalization. The median age was lower in the group of surviving patients than in the group of non surviving patients, with 51,5 years (range 36 to 66,75) and 81,5 years (range 69,5 to 83,25), respectively (p=0,002). Hospital stay was 32,50 days (range 8,25 to 64,25) in the group of non-surviving patients and was 6,5 days (range 4 to 15,75) (p=0,045) in the group with no deaths. CONCLUSIONS: The elevated mortality found in the hospitalized CDAD patients in the Intensive Care Unit makes the maintenance of strict surveillance in this population imperative so there can be opportune detection and treatment. PMID- 22672851 TI - [Laparoscopic apendicectomy vs open approach for the treatment of acute appendicitis]. AB - BACKGROUND: There is no international consensus on the approach of choice for performing appendectomy. AIMS: To analyze and compare open and laparoscopic approaches in the surgical treatment of acute appendicitis. MATERIAL AND METHODS: A retrospective study was carried out on patients over 14-years-old operated on for suspected acute appendicitis between January 2007 and December 2009. Variables were: age, sex, body mass index, specialized surgeon or resident in training, progression duration, conversion rate, use of drains, abdominal cavity irrigation, macroscopic appearance of the appendix, onset time of anesthesia, ASA classification, postoperative hospital stay, resumption of intake of liquids, and complications. The patients were divided into two groups: laparoscopic approach (LA) and open approach (OA). RESULTS: A total of 533 patients were enrolled (290 LA and 243 OA). Onset time of anesthesia was 75 min (30-190 min) in LA vs 55 min (20-160 min) in OA (p<0,0001). COMPLICATIONS: intraabdominal abscesses in 17 LA cases vs 13 OA cases (p=0,79); surgical wound alterations in 16 LA cases vs 47 OA cases (p=0,0001); incisional hernias in 2 LA cases (1%) vs 10 OA cases (p=0,008). There were no statistically significant differences in postoperative hospital stay (3 days), resumption of intake of liquids (1 day) or readmission rate (8%). CONCLUSIONS: There are fewer surgical wound alterations and incisional hernias with the laparoscopic approach, but there is higher cost, lengthier surgery duration, and a longer learning curve. Our results cannot provide a clear indication for one approach or the other, and therefore each case must be evaluated on an individual basis. PMID- 22672852 TI - [Clostridium difficile-associated diarrhea infection: is it time for us to start worrying in Mexico?]. PMID- 22672853 TI - [Morbidity and mortality in a series of patients suffering from intraperitoneal neoplasia treated with peritoneal cytoreduction and hyperthermic intraperitoneal chemotherapy at the Fundacion Santa Fe de Bogota Teaching Hospital (ONCOLGroup- ATIA study)]. AB - BACKGROUND: The procedure of radical peritonectomy followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is considered the standard treatment for peritoneal cancers. AIMS: To evaluate various outcomes in a cohort of patients with peritoneal tumors treated with HIPEC. METHODS: Twenty-four patients consecutively treated with radical peritonectomy plus HIPEC within the time frame of November 2007 to July 2010 were enrolled; 15 (62%) had tumors of appendicular origin, 4 (16.7%) had primary peritoneal tumors, 2 had ovarian carcinomas and there was one case of colon cancer, one carcinosarcoma and one hemangioendothelioma. Mean age was 53 years (range: 26-68) and median follow-up was 14.2 months (range: 1-32). Demographic data, histology, peritoneal cancer index (PCI), surgical procedure characteristics, recurrence-free survival (RFS), and overall survival (OS) were all evaluated. Short-term morbidity and mortality were also determined. RESULTS: Complete cytoreduction was achieved in 18 patients (75%). Mean PCI was 15 (<10: 41% and >10: 58%), and the median (range) for surgery duration, length of stay in the Intensive Care Unit, parenteral nutritional support, and hospital stay were 12,5 (7-20) hours, 11,4 (2-74) days, 13,8 (12-65) days, and 29,1 (10-90) days, respectively. One patient (4%) died 6 months after the procedure, due to multiple associated complications. Considerable morbidity was seen in 52% of cases, including thromboembolic events (41%), catheter-related bacteremia (29%), fistulas (29%), and nephrotoxicity (25%). Six patients (25%) recurred after a median of 21 months of RFS. CONCLUSIONS: Cytoreductive surgery plus HIPEC in well-selected patients presenting with tumors that affect the peritoneum is a procedure that can be carried out in Colombia with an adequate safety and effectiveness profile. Mortality was similar to that reported in the international literature. PMID- 22672854 TI - Effect of antispasmodic agents, alone or in combination, in the treatment of Irritable Bowel Syndrome: systematic review and meta-analysis. AB - INTRODUCTION: Irritable bowel syndrome (IBS) is characterized by recurrent abdominal pain, bloating, and changes in bowel habit. AIMS: To determine the clinical effectiveness of the antispasmodic agents available in Mexico for the treatment of IBS. METHODS: We carried out a systematic review and meta-analysis of randomized controlled clinical trials on antispasmodic agents for IBS treatment. Clinical trials identified from January 1960 to May 2011 were searched for in MEDLINE, the Cochrane Library, and in the ClinicalTrials.gov registry. Treatment response was evaluated by global improvement of symptoms or abdominal pain, abdominal distention/bloating, and frequency of adverse events. The effect of antispasmodics vs placebo was expressed in OR and 95% CI. RESULTS: Twenty seven studies were identified, 23 of which fulfilled inclusion criteria. The studied agents were pinaverium bromide, mebeverine, otilonium, trimebutine, alverine, hyoscine, alverine/simethicone, pinaverium/simethicone, fenoverine, and dicyclomine. A total of 2585 patients were included in the meta-analysis. Global improvement was 1.55 (CI 95%: 1.33 to 1.83). Otilonium and the alverine/simethicone combination produced significant values in global improvement while the pinaverium/simethicone combination showed improvement in bloating. As for pain, 2394 patients were included with an OR of 1.52 (IC 95%: 1.28 a 1.80), favoring antispasmodics. CONCLUSIONS: Antispasmodics were more effective than placebo in IBS, without any significant adverse events. The addition of simethicone improved the properties of the antispasmodic agents, as seen with the alverine/simethicone and pinaverium/simethicone combinations. PMID- 22672855 TI - A reason for choosing peritoneal dialysis: lessons after the Japan earthquake and the Fukushima nuclear accident. PMID- 22672856 TI - High morbidity and mortality associated with an outbreak of influenza A(H3N2) in a psycho-geriatric facility. AB - In spring 2008, an influenza A subtype H3N2 outbreak occurred in a long stay psycho-geriatric ward and two wards in the intellectual disability services (IDS), part of a large psychiatric hospital. The attack rate in the index ward was 90% (18/20) for patients and 35% (7/20) for staff. It was 14% (1/7) and 17% (2/12) in the affected IDS wards for patients and 0% (0/20) and 4% (1/25) for staff. Many of the laboratory-confirmed cases did not have a fever >38 degrees C, a typical sign of influenza. Control measures included oseltamivir treatment for cases and prophylaxis for contacts, standard and droplet infection control precautions, active surveillance for early detection and isolation of potential cases. As a result, the outbreak did not spread throughout the hospital. Although the staff vaccination rate (10%) prior to the outbreak was low, we observed a much lower vaccine effectiveness rate in the patients (11%) than in the staff (100%) in the index ward. Vaccination of residents and staff of such facilities remains the key influenza prevention strategy. PMID- 22672857 TI - [Tilt training increases vasoconstrictor reserve in patients with neurocardiogenic syncope]. AB - Neurocardiogenic syncope (NCS) is a common clinical entity resulting from an excessive reflex autonomic response, particularly during orthostatism. Treatment options are controversial and of limited effectiveness. Tilt training (TT) is a promising option to treat these patients. However, its mechanism of action and clinical impact remain unclear. OBJECTIVE: To characterize hemodynamic and autonomic responses during a TT program in patients with NCS refractory to conventional measures. METHODS: We studied 28 patients (50% male, mean age 41+/ 14 years) without structural heart disease, with NCS documented by tilt testing. The TT program included 9 tilt sessions (3 times a week, 30 min) (60 degrees - 6 sessions, 70 degrees - 3 sessions), under ECG and blood pressure monitoring combined with home orthostatic self-training and 10 degrees head-up during sleep. Systolic volume, cardiac output, total peripheral resistance, baroreflex sensitivity and heart-rate variability were computed. Patients were reassessed at 1 month and every 6 months for a maximum of 36 months (24+/-12 months). RESULTS: Over the course of the TT program there was a significant increase in total peripheral resistance (1485+/-225 vs. 1591+/-187 dyn.s.cm(-5), p<0.05), with a decrease in standard deviation (206+/-60 vs. 150+/-42, p<0.05). During follow-up, syncope recurred in five patients (19%), with a significant reduction in the number of episodes (4.0+/-3.2/patient in the 12 months before TT vs. 1.4+/ 0.8/patient post-TT, p<0.05). CONCLUSION: In refractory NCS, TT may be an effective therapeutic option, with long-term benefits. These results appear to be due to an increase in vasoconstrictor reserve combined with a reduction in its variance. PMID- 22672858 TI - Structural characterization of alkaline hydrogen peroxide pretreated grasses exhibiting diverse lignin phenotypes. AB - BACKGROUND: For cellulosic biofuels processes, suitable characterization of the lignin remaining within the cell wall and correlation of quantified properties of lignin to cell wall polysaccharide enzymatic deconstruction is underrepresented in the literature. This is particularly true for grasses which represent a number of promising bioenergy feedstocks where quantification of grass lignins is particularly problematic due to the high fraction of p-hydroxycinnamates. The main focus of this work is to use grasses with a diverse range of lignin properties, and applying multiple lignin characterization platforms, attempt to correlate the differences in these lignin properties to the susceptibility to alkaline hydrogen peroxide (AHP) pretreatment and subsequent enzymatic deconstruction. RESULTS: We were able to determine that the enzymatic hydrolysis of cellulose to to glucose (i.e. digestibility) of four grasses with relatively diverse lignin phenotypes could be correlated to total lignin content and the content of p-hydroxycinnamates, while S/G ratios did not appear to contribute to the enzymatic digestibility or delignification. The lignins of the brown midrib corn stovers tested were significantly more condensed than a typical commercial corn stover and a significant finding was that pretreatment with alkaline hydrogen peroxide increases the fraction of lignins involved in condensed linkages from 88-95% to ~99% for all the corn stovers tested, which is much more than has been reported in the literature for other pretreatments. This indicates significant scission of beta-O-4 bonds by pretreatment and/or induction of lignin condensation reactions. The S/G ratios in grasses determined by analytical pyrolysis are significantly lower than values obtained using either thioacidolysis or 2DHSQC NMR due to presumed interference by ferulates. CONCLUSIONS: It was found that grass cell wall polysaccharide hydrolysis by cellulolytic enzymes for grasses exhibiting a diversity of lignin structures and compositions could be linked to quantifiable changes in the composition of the cell wall and properties of the lignin including apparent content of the p hydroxycinnamates while the limitations of S/G estimation in grasses is highlighted. PMID- 22672859 TI - Meta-analysis of human lung cancer microRNA expression profiling studies comparing cancer tissues with normal tissues. AB - BACKGROUND: Lung cancer is the major cause of cancer death globally, it is often diagnosed at an advanced stage and has one of the lowest survival rates of any type of cancer. The common interest in the field of lung cancer research is the identification of biomarkers for early diagnosis and accurate prognosis. There is increasing evidence to suggest that microRNAs play important and complex roles in lung cancer. METHODS: A meta-analysis was conducted to review the published microRNA expression profiling studies that compared the microRNAs expression profiles in lung cancer tissues with those in normal lung tissues. A vote counting strategy that considers the total number of studies reporting its differential expression, the total number of tissue samples used in the studies and the average fold change was employed. RESULTS: A total of 184 differentially expressed microRNAs were reported in the fourteen microRNA expression profiling studies that compared lung cancer tissues with normal tissues, with 61 microRNAs were reported in at least two studies. In the panel of consistently reported up regulated microRNAs, miR-210 was reported in nine studies and miR-21 was reported in seven studies. In the consistently reported down-regulated microRNAs, miR-126 was reported in ten studies and miR-30a was reported in eight studies. Four up regulated microRNAs (miR-210, miR-21, miR-31 and miR-182) and two down-regulated mcroiRNAs (miR-126 and miR-145) were consistently reported both in squamous carcinoma and adenocarcinoma-based subgroup analysis, with the other 14 microRNAs solely reported in one or the other subset. CONCLUSIONS: In conclusion, the top two most consistently reported up-regulated microRNAs were miR-210 and miR-21. The results of this meta-analysis of human lung cancer microRNA expression profiling studies might provide some clues of the potential biomarkers in lung cancer. Further mechanistic and external validation studies are needed for their clinical significance and role in the development of lung cancer. PMID- 22672860 TI - Fetal and neonatal endocrine disruptors. AB - Endocrine disruptors are substances commonly encountered in every setting and condition in the modern world. It is virtually impossible to avoid the contact with these chemical compounds in our daily life. Molecules defined as endocrine disruptors constitute an extremely heterogeneous group and include synthetic chemicals used as industrial solvents/lubricants and their by-products. Natural chemicals found in human and animal food (phytoestrogens) also act as endocrine disruptors. Different from adults, children are not exposed only to chemical toxins in the environment but may also be exposed during their intrauterine life. Hundreds of toxic substances, which include neuro-immune and endocrine toxic chemical components that may influence the critical steps of hormonal, neurological and immunological development, may affect the fetus via the placental cord and these substances may be excreted in the meconium. Children and especially newborns are more sensitive to environmental toxins compared to adults. Metabolic pathways are immature, especially in the first months of life. The ability of the newborn to metabolize, detoxify and eliminate many toxins is different from that of the adults. Although exposures occur during fetal or neonatal period, their effects may sometimes be observed in later years. Further studies are needed to clarify the effects of these substances on the endocrine system and to provide evidence for preventive measures. PMID- 22672861 TI - Plasma kisspeptin levels in girls with premature thelarche. AB - OBJECTIVE: Premature thelarche (PT) is defined as isolated breast development without secondary sex characteristics in girls below the age of eight. We aimed to determine whether the level of kisspeptin, which plays a role in the release of gonadotropins, is associated with PT. METHODS: The patient group included children with PT aged 3-8 years (n=20) and the control group included healthy children in the same age range (n=20). Height standard deviation scores (HSDSs), bone maturation and growth velocity were evaluated in the two groups. Basal follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), prolactin (PRL), and sex hormone-binding globulin (SHBG) levels were also measured in the two groups by immunochemiluminometric assay (ICMA). A gonadotropin-releasing hormone (GnRH) test was also conducted in the patient group and the peak levels of FSH and LH were determined. Kisspeptin levels were measured using enzyme immunoassay (EIA). RESULTS: No differences were found between the groups in terms of age, HSDS, annual growth rate and bone age. While the plasma basal FSH, LH and E2 levels in the patient and control groups did not show statistically significant differences, PRL levels were higher in the patient group (p<0.05). Peak LH response to GnRH test was at the prepubertal level (<5 ng/mL) in patients with PT. In the patient group, kisspeptin levels were significantly higher compared to the levels in the control group (2.96 +/- 1.21 ng/dL vs. 1.19 +/- 0.41 ng/dL, p<0.05), and kisspeptin levels showed a significant correlation with PRL, FSH, LH, and E2 levels (p<0.05). CONCLUSIONS: In this study, plasma kisspeptin levels were found to be higher in patients with PT and to show a positive correlation with increased PRL levels. Kisspeptin is one of the neuropeptides that plays a role in the onset of puberty. Our results support the hypothesis that PT may result from the temporary activation of central stimulants. PMID- 22672862 TI - The role of interleukin-6 and C-reactive protein in non-thyroidal illness in premature infants followed in neonatal intensive care unit. AB - OBJECTIVE: To investigate the role of interleukin-6 (IL-6) and C-reactive protein (CRP) in non-thyroidal illness (NTI) in premature infants. METHODS: Serum levels of IL-6 and CRP, thyroid-stimulating hormone (TSH), total thyroxine (T4), free T4 (fT4), total triiodothyronine (T3), and free T3 (fT3) were determined at the 1st, 2nd and 4th weeks of postnatal life in 148 premature infants born before 33 weeks of gestation. RESULTS: At the 1st week, serum T3 was negatively correlated with IL-6 (r= -0.33, p= 0.001) and CRP (r= -0.17, p= 0.03). Serum T3 was negatively and more strongly correlated with IL-6 (r= -0.49, p= 0.001) and CRP (r=- 0.33, p= 0.03) at the 2nd week, at which time sepsis frequency and low T3 rates were the highest. At the 4th week, mortality rate was higher among infants with lower T3 levels. CONCLUSIONS: High IL-6 and CRP values related to neonatal sepsis might have a significant role in the pathogenesis of NTI in premature infants. PMID- 22672863 TI - Developmental defects of the thyroid gland: relationship with advanced maternal age. AB - OBJECTIVE: Developmental defects of the thyroid gland are the most frequent causes of permanent congenital hypothyroidism. This study aimed to investigate the epidemiological features of patients with thyroid dysgenesis (TD). METHODS: Medical records of 234 patients with TD followed between the years 2008 and 2010 were evaluated retrospectively. Diagnosis was made by ultrasonography. RESULTS: Of 234 patients, 120 (51.3%) were male and 114 (48.7%) were female. Male to female ratio was 1.08 and there were no significant differences in epidemiologic and clinical findings between girls and boys. One hundred eighty-three patients (78.2%) were diagnosed as hypoplasia, 35 (14.9%) as thyroid agenesis, 4 as ectopic thyroid gland and 12 as hemiagenesis. The mean maternal age of the group was 28.9 +/- 0.4 years (range 18 to 45 years), which is significantly higher than the recently reported mean maternal ages for Turkish women. CONCLUSIONS: Advanced maternal age was more prevalent in patients with TD. Our clinical and epidemiologic findings suggested no evidence of sexual dimorphism. PMID- 22672864 TI - Serum visfatin levels, adiposity and glucose metabolism in obese adolescents. AB - OBJECTIVE: Visfatin, an adipokine, has insulin-mimetic effects. The main determinants of both the production and the physiologic role of visfatin are still unclear. The aim of this study is to determine the relation of serum visfatin to adiposity and glucose metabolism. METHODS: 40 pubertal adolescents (20 females, 20 males; age range: 9-17 years) with exogenous obesity and 20 age- and sex-matched healthy adolescents (10 females, 10 males) were enrolled in the study. Oral glucose tolerance test (OGTT) was performed in the obese group. Serum glucose, insulin and visfatin levels were analyzed in the fasting state in the controls and at 0, 60 and 120 minutes during the OGTT in the obese group. RESULTS: The obese group had higher serum visfatin levels than the control group [11.6 (3.3-26) ng/mL vs. 7.5 (3.3-10.5) ng/mL, p<0.001[. Visfatin levels were correlated positively with body mass index, waist/hip ratio, insulin, and homeostasis model assessment for insulin resistance and negatively with glucose/insulin ratio in the combined group (obese subjects plus controls). Visfatin levels were essentially similar in obese subjects with and without insulin resistance (p>0.05). Serum visfatin levels did not change at 60 and 120 minutes of the OGTT compared to the baseline levels (p>0.05). CONCLUSIONS: Serum visfatin levels are elevated in obese adolescents and do not change with acute changes in glucose metabolism. Visfatin levels are related with adiposity and glucose metabolism parameters. However, the role and contribution of adiposity and glucose metabolism to the circulating visfatin levels in obese patients remain to be explored. PMID- 22672865 TI - Characteristics of children with type 1 diabetes and persistent suboptimal glycemic control. AB - OBJECTIVE: This study aims to determine the relationship between the duration of persistent poor glycemic control in type 1 diabetes mellitus (T1DM) children and the likelihood of subsequent improvement. METHODS: A retrospective cohort study was conducted on T1DM patients aged 6-18 years, followed for at least six visits at Children's National Medical Center (Washington, DC) with at least one hemoglobin A1c (HbA1c) >= 10% after the first year since the initial visit (n=151). Medical records of patients with subsequently improved glycemic control were reviewed (n=39). RESULTS: Patients aged 12-18 years, females, and Medicaid patients were twice as likely to be in persistently poor control as patients aged 6-11 years, males, and privately insured patients, respectively. Each additional visit with HbA1c >= 10% and one percentage point increase in the mean HbA1c reduced the likelihood of subsequent improvement by 20% and 50%, respectively. Of the 39 patients with improved control, only 5 (13%) sustained their improvement for >= 2 years. Multiple contributing factors for improved control were identified, but no one factor explained improved control in > 25% of patients. CONCLUSION: This study suggests that the longer the duration of poor control, the more difficult it is to reverse the underlying factors of poor diabetes management. Strategies to improve regular clinic attendance along with reinforcement of changes which resulted in improved control are critical. Adolescents, females, and Medicaid patients in particular should be targeted for sustained intervention. PMID- 22672866 TI - SLC34A3 intronic deletion in a new kindred with hereditary hypophosphatemic rickets with hypercalciuria. AB - OBJECTIVE: Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is an autosomal recessive form of hypophosphatemia with hyperphosphaturia, hypercalciuria, and hypercalcemia. In two reports on six affected kindreds with HHRH, the disease was mapped to chromosome 9q34, which contains the SLC34A3 gene that encodes the renal type 2c sodium-phosphate cotransporter. Our objective was to define the clinical course of these cases in a family with HHRH and to screen for SLC34A3 gene in order to determine whether these mutations are responsible for HHRH. METHODS: After clinical and biochemical evaluations, the entire SLC34A3 gene was screened using PCR amplification followed by direct sequencing technique. In this paper, we describe a new kindred with HHRH and a case of progressive and complicated HHRH presenting at age 27 years. RESULTS: We found 101-bp deletion in intron 9 of the SLC34A3 gene. The index patient was homozygous for this mutation which has been previously reported in a Caucasian population. This is the first report for presence of SLC34A3 intron 9 deletion in an Iranian population. CONCLUSIONS: These data showed that HHRH can be easily missed or underdiagnosed. Genetic evaluation of patients with familial hypercalciuria, hypophosphatemia and nephrolithiasis is needed for further information on the prevalence and management of this rare disorder. PMID- 22672867 TI - Testicular adrenal rest tumors in patients with congenital adrenal hyperplasia. AB - OBJECTIVE: Early diagnosis and treatment of testicular adrenal rest tumors (TART) is important for gonadal functions and fertility protection in boys with congenital adrenal hyperplasia (CAH). In this descriptive study, we investigated the prevalence of TART in boys with 21-hydroxylase deficient (21OHD) CAH followed in our pediatric endocrine clinic. METHODS: The study group consisted of 14 male patients with a mean age of 9.6 +/- 5.1 (range: 0.8-18.3) years. Six (42.9%) of the 14 patients were diagnosed as having salt-wasting type (SW) and eight (57.1%) patients - as having the simple virilizing (SV) form of 21OHD. Mean age at diagnosis was 2.9 +/- 2.7 (range: 0.03-6.3) years. Two different radiologists performed scrotal ultrasonography. Chronological age, bone age, and anthropometric measurements were evaluated. Serum adrenocorticotropic hormone (ACTH), 17-alpha-hydroxyprogesterone (17OHP) and androstenedione levels were also evaluated in all patients during the follow-up period. RESULTS: Scrotal ultrasonography revealed bilateral TART in two patients (14.3%) and testicular microlithiasis (TM) in four patients (28.6%). One patient had both TART and TM bilaterally. During the follow-up period, the mean serum adrenocorticotropic hormone, 17OHP and androstenedione levels in the total group of patients were 130.0 +/- 179.1 pg/mL (21.7-726.5), 5.8 +/- 3.3 ng/mL (0.8-11.4) and 4.3 +/- 4.1 (0.2-11.0) ng/mL, respectively. CONCLUSIONS: Microlithiasis or TART may be frequently encountered during the follow-up of patients with CAH. In order to prevent late complications including infertility, we suggest that ultrasonographic evaluations be performed yearly in all male CAH patients. PMID- 22672868 TI - Wolcott-Rallison syndrome due to a novel mutation (R491X) in EIF2AK3 gene. AB - Wolcott-Rallison syndrome (WRS) is a rare autosomal recessive disorder characterized by early-onset diabetes, spondyloepiphyseal dysplasia, tendency to skeletal fractures secondary to osteopenia, and growth retardation. Mutations in the eukaryotic translation initiation factor 2alpha kinase (EIF2AK3) gene are responsible for this disorder. Here, we describe a boy with neonatal diabetes, diagnosed at 2 months of age, who developed severe growth retardation and a skeletal fracture during the follow-up period. The patient's skeletal X-ray revealed findings of skeletal dysplasia. A clinical diagnosis of WRS was confirmed by the identification of a novel homozygous nonsense mutation (R491X) in exon 9 of the EIF2AK3 gene. The aim of this report is to raise the awareness for Wolcott-Rallison syndrome in cases presenting with isolated neonatal diabetes. This patient demonstrates that the other findings of this syndrome might be obscured by a diagnosis of isolated neonatal diabetes. PMID- 22672869 TI - Early onset of liver steatosis in a Japanese girl with maturity-onset diabetes of the young type 3 (MODY3). AB - Maturity-onset diabetes of the young type 3 (MODY3) is caused by heterozygous mutation in the HNF1A gene. Liver adenomatosis has been reported in MODY3 patients. The patient reported in this paper is a Japanese girl who first developed hepatomegaly, fatty liver, and hepatic dysfunction at age 5 years. Liver biopsy demonstrated steatosis and degeneration of hepatocytes. At that time, blood glucose and HbA1c levels were within normal ranges. Elevated HbA1c was noticed 4 years later, but islet cell and glutamic acid decarboxylase antibodies were not detected in the serum. Therefore, MODY3 was suspected and subsequent analysis of the HNF1A gene identified a heterozygous germline splice donor-site mutation in intron 9. MODY3 patients should be screened by non invasive liver imaging, and careful follow-up of liver disease should be performed. PMID- 22672870 TI - Permanent neonatal diabetes mellitus: same mutation, different glycemic control with sulfonylurea therapy on long-term follow-up. AB - Permanent neonatal diabetes mellitus (PNDM) is a rare condition presenting before six months of age. Mutations in the genes encoding the ATP-sensitive potassium (KATP) channel are the most common causes. Sulfonylurea (SU) therapy leads to dramatic improvement in diabetes control and quality of life in most patients who carry these mutations. Here, we report the long-term follow-up results of two siblings with PNDM who were treated with insulin until ABCC8 gene mutation was identified, and were successfully transferred to oral SU therapy. After 3.5 years of follow-up on SU, one patient had a very good response, while the other one had a poor response. Bad compliance to diet was thought to be the most probable reason for poor glycemic control in this patient. In conclusion, molecular genetic diagnosis in all patients with PNDM is recommended. Compliance to treatment should be an important aspect of the follow-up of these patients. PMID- 22672871 TI - Congenital hypothyroidism due to maternal radioactive iodine exposure during pregnancy. AB - Radioactive iodine (RAI) is used effectively in the treatment of hyperthyroidism and thyroid cancer, but it is contraindicated during pregnancy. RAI treatment during pregnancy can lead to fetal hypothyroidism, mental retardation and increased malignancy risk in the infant. Pregnancy tests must be performed before treatment in all women of reproductive age. However, at times, RAI is being used before ruling out pregnancy. We herein present a male newborn infant with congenital hypothyroidism whose mother was given a three-week course of methimazole therapy for her multiple hyperactive nodules and subsequently received 20 mCi RAI during the 12th week of her pregnancy. The patient was referred to our neonatology unit at age two weeks when his thyrotropin (TSH) level was reported to be high in the neonatal screening test. Physical examination was normal. Laboratory investigations revealed hypothyroidism (free triiodothyronine 1.55 pg/mL, free thyroxine 2.9 pg/mL, TSH 452 mU/L, thyroglobulin 20.1 ng/mL). The thyroid gland could not be visualized by ultrasonography. L-thyroxine treatment was initiated. PMID- 22672872 TI - Diabetes program at schools in Turkey. PMID- 22672873 TI - Proposal for an in vivo histopathologic scoring system for skin aging by means of confocal microscopy. AB - BACKGROUND: Many instrumental devices have been testing in analysing and quantifying the skin aging signs. However, histopathology still remains the only methods that allow a microscopic assessment of the skin. However, a skin biopsy is not feasible in aesthetically critical areas such as the face. Recently, confocal microscopy has been discovered as a noninvasive tool with a nearly histologic resolution. Distinct morphologic confocal aspects on facial skin have been described and correlated with the histopathologic counterparts. OBJECTIVES: In our study we aim to develop an easy to use confocal aging score to quantify the skin aging related signs. METHODS: A sample of facial skin of fifty volunteers has been subjected to confocal imaging. Combining the previously identified confocal features, three different semi-quantitative scores were calculated: - epidermal disarray score (irregular honeycombed pattern + epidermal thickness + furrow pattern); - epidermal hyperplasia score (mottled pigmentation + extent of polycyclic papillary + epidermal thickness; - collagen score (curled fibers, 2 for huddles of collagen, 1 for coarse collagen structures, and 0 for thin reticulated collagen) RESULTS: The epidermal disarray score showed a stable trend up to 65 years and a dramatic increase in the elderly subjects epidermal. Hyperplasia score was characterized by an ascending trend from younger subjects to middle age. The total collagen score showed a progressive trend with age with a different proportion of distinct collagen type. CONCLUSIONS: RCM is a powerful, noninvasive technique that could permit to microscopically quantify the aging signs and to test cosmetic efficacy. PMID- 22672874 TI - The TWEAK/Fn14 pathway as an aggravating and perpetuating factor in inflammatory diseases: focus on inflammatory bowel diseases. AB - The TWEAK/Fn14 pathway is a ligand/receptor pair of the TNFSF that has emerged as a prominent player in normal and pathological tissue remodeling. TWEAK/Fn14 pathway activation drives many processes relevant to autoimmune and inflammatory diseases. IBDs, including CD and UC, are chronic, relapsing inflammatory diseases of the GI tract. These diseases differ in their clinical, macroscopic, and histopathological presentation; however, pathological processes that prominently contribute, more or less in each case, include breakdown of the mucosal epithelial barrier, chronic inflammation, and tissue remodeling with fibrosis. TWEAK may promote the pathogenesis of IBD by signaling through Fn14, which can be up-regulated on IECs, thereby contributing to breakdown of the mucosal barrier; the induction of IEC-derived mediators that promote chronic inflammation and shape gut immunity against commensal flora; and delayed healing and fibrosis. TWEAK may also exert its action on endothelial and stromal cell types, including smooth muscle cells and fibroblasts, to promote chronic inflammation, dysregulated tissue repair, and fibrosis. Here, we review the data supporting an emerging role of the TWEAK/Fn14 pathway in autoimmune and inflammatory diseases, with a particular focus on IBD, and discuss how it interplays with other prominent pathways, including IL-13, TNF-alpha, and TGF-beta, to aggravate and perpetuate the pathological processes underlying IBD. PMID- 22672876 TI - The mitochondrial Ca(2+) uniporter. AB - Mitochondrial Ca(2+) uptake plays a fundamental role in the regulation of energy production and cell survival. Under physiological conditions, mitochondrial Ca(2+) uptake occurs by a uniport mechanism driven electrophoretically by the membrane potential created by the respiratory chain. The activity and the biochemical properties of the mitochondrial calcium uniporter (MCU) were extensively characterized for decades but the molecular identity of the channel has remained elusive. Here, we review the recent discovery of the mitochondria Ca(2+) uniporter that represents a groundbreaking result for the molecular understanding of mitochondrial Ca(2+) homeostasis and will provide insight into the role of mitochondrial Ca(2+) deregulation in the pathogenesis of human disorders. PMID- 22672875 TI - Eosinophil crystalloid granules: structure, function, and beyond. AB - Eosinophils are granulocytes associated with host defense against parasitic helminths with allergic conditions and more recently, with immunoregulatory responses. Eosinophils are distinguished from leukocytes by their dominant population of cytoplasmic crystalloid (also termed secretory, specific, or secondary) granules that contain robust stores of diverse, preformed cationic proteins. Here, we provide an update on our knowledge about the unique and complex structure of human eosinophil crystalloid granules. We discuss their significance as rich sites of a variety of receptors and review our own recent research findings and those of others that highlight discoveries concerning the function of intracellular receptors and their potential implications in cell signaling. Special focus is provided on how eosinophils might use these intracellular receptors as mechanisms to secrete, selectively and rapidly, cytokines or chemokines and enable cell-free extracellular eosinophil granules to function as independent secretory structures. Potential roles of cell-free eosinophil granules as immune players in the absence of intact eosinophils will also be discussed. PMID- 22672877 TI - Introduction: regulated exocytosis. AB - Calcium ions regulate secretory processes in several ways. Most prominently they (i) trigger the release of vesicle contents rapidly and in a highly cooperative way and they (ii) control priming steps, which prepare vesicles for release. The importance of using assays with high time resolution for separating these distinct roles is pointed out here. PMID- 22672878 TI - Norms for imaging markers of brain reserve. AB - Brain reserve allows some people to be more resilient to neurodegeneration processes and brain diseases. Structural markers of brain reserve are hippocampus, lateral ventricles, and white matter lesions volume (HV, LVV, WMLV). Subjects in the low end of the distribution of these markers are at higher risk to develop brain diseases such as Alzheimer's disease. We described the distribution of the above markers in a large group of cognitively-intact persons. A sample of 158 people aged between 40 to 90 years (mean +/- SD: 60 +/- 12 years, education 9 +/- 4 years, MMSE score 28 +/- 2) belonging to the Italian Brain Normative Archive was selected. HV, LVV, and WMLV were measured with validated procedures. The HV and LVV were measured by manual segmentation and the Freesurfer software, respectively, and normalized by head size; WMLV was measured with semi-automated thresholding. Test-retest reliability was >0.83 for all measures. No relationship was found between HV and age, whereas a significant relationship was found for LVV and WMLV (ventricle left: B 0.02, 95% CI 0.22 to 0.34; ventricle right: B 0.02 95% CI 0.23 to 0.34 p < 0.001; WML: B 0.04; 95% CI 0.03 to 0.06 p < 0.005). The 5th percentile threshold indicating lower brain reserve were: (i) HV below 2,260 mm(3) at 40 and 2,000 mm(3) at 90; (ii) LVV above 17,000 mm(3) at 40 and 60,000 mm(3) at 90; and (iii) WMLV above 1,200 mm(3) at 40 and 8,700 mm(3) at 90. Normative data of brain reserve markers can be used to estimate the brain resilience to neurodegeneration. PMID- 22672879 TI - GABA attenuates amyloid toxicity by downregulating its endocytosis and improves cognitive impairment. AB - GABA (gamma-aminobutyric acid) receptor modulators have been investigated as a potential treatment strategy in Alzheimer's disease (AD). In the present study, we found that GABA levels were different in wild type (WT) and AbetaPP/PS1 mouse brains. GABA downregulated amyloid-beta (Abeta) uptake in neurons through the receptor for advanced glycation end-products. Therefore, relative high levels of GABA decreased cytotoxicity induced by Abeta in WT mice. GABA treatment decreased basal levels of cell death and the cell death induced by hydrogen peroxide in WT and AbetaPP/PS1 neurons. Application of GABA during early life before 2 months of age can improve cognitive function significantly in AbetaPP/PS1 mice. However, GABA treatment at 6 and 8 months of age cannot improve water maze performance. Activating or suppressing GABAA receptors by optogenetic methods also confirmed that GABA activation before 2 months of age increased water maze performance in AbetaPP/PS1 mice. Our data suggest that GABA administration during early life can be a potential treatment for AD. PMID- 22672881 TI - Intensification of polypharmacy glucose-lowering treatment in type-2 diabetes: when to be cautious? PMID- 22672882 TI - Estimation of a safe level for occupational exposure to vinyl chloride using a benchmark dose method in central China. AB - OBJECTIVES: The aim of this study was to estimate a benchmark dose (BMD) for chromosome damage induced by vinyl chloride monomer (VCM) in VCM-exposed workers in central China and validate the published results in Shanghai. METHODS: VCM exposed workers who had been exposed to VCM for at least one year (n=463) and matched subjects not exposed to VCM or other toxins (n=273) were asked to participate in this study. Micronucleus (MN) frequency based on the cytokinesis block micronucleus assay (CBMN) was used as a biomarker for chromosome damage induced by VCM exposure. RESULTS: The MN frequency in the VCM-exposed workers was significantly higher than that in the control group, and multivariate Poisson regression suggested that gender, smoking status and VCM exposure were the significant factors influencing the risk of increased MN frequency. When subjects were further stratified according to gender and smoking status, the results showed that female VCM-exposed workers were more susceptible than the males to the risk of increased MN frequency. The MN frequency of smokers was significantly higher than that of nonsmokers in the control group. Our study also suggested that there was a strong dose-response relationship between VCM CED and the increased risk of MN frequency in the total group, males and females. The BMDL(10) was found to be 630.6, 670.2 and 273.7 mg-year for all VCM-exposed workers, males and females, respectively. CONCLUSIONS: These results invite further scrutiny of the current VCM occupational exposure limits and warrant further study of the risk of VCM genotoxicity and carcinogenicity. PMID- 22672880 TI - Recent advances in imaging Alzheimer's disease. AB - Advances in brain imaging technology in the past five years have contributed greatly to the understanding of Alzheimer's disease (AD). Here, we review recent research related to amyloid imaging, new methods for magnetic resonance imaging analyses, and statistical methods. We also review research that evaluates AD risk factors and brain imaging, in the context of AD prediction and progression. We selected a variety of illustrative studies, describing how they advanced the field and are leading AD research in promising new directions. PMID- 22672883 TI - Psychological outcome of injured workers at 3 months after occupational injury requiring hospitalization in Taiwan. AB - INTRODUCTION: After a traumatic event, a significant proportion of victims develop psychiatric disorders. Trauma has been an important ailment among workers. This study aimed to determine the prevalence of post-traumatic stress disorder (PTSD) and other psychiatric disorders at three months after occupational injuries. METHODS: Our study candidates were injured workers in Taiwan who were hospitalized for 3 days or longer and received hospitalization benefits from the Labor Insurance program. A two-staged survey study was conducted. A self-reported questionnaire including the Brief Symptom Rating Scale (BSRS-50) and Post-traumatic Symptom Checklist (PTSC) was sent to workers at 3 months after injury. Those who met the criteria were recruited for the second stage phone interview with a psychiatrist using the Mini-international Neuropsychiatrie Interview (MINI). RESULTS: A total of 2001 workers completed the questionnaire (response rate 45.5%). Among them, 357 (17.8%) fulfilled the criteria for the MINI interview and were invited. A total of 148 (41.5%) completed the phone interview. The estimated rates of PTSD, partial PTSD (PPTSD), major depression, comorbid PTSD/PPTSD and major depression, and either PTSD/PPTSD or major depression were 2.7, 4.1, 3.0, 2.3, and 7.5%, respectively. The estimated rates of either PTSD/PPTSD or major depression among workers who suffered from intracranial injury, fracture, burn, crushing injury, and open wound of upper limbs were 10.4, 6.9, 5.9, 5.8 and 0%, respectively. CONCLUSIONS: At three months after occupational injuries, a significant proportion of workers suffered from psychiatric disorders. The rates of psychiatric disorders occurring after intracranial injuries were significantly higher than those occurring after non-intracranial injuries. PMID- 22672884 TI - Effects of individual and work-related factors on incidence of shoulder pain in a large working population. AB - OBJECTIVES: The aim of this study was to assess the effects of individual and work-related factors on the incidence of shoulder pain in a large French working population. METHODS: A total of 3,710 workers of a French region were randomly included in a cross-sectional study between 2002 and 2005. They completed a self administered questionnaire about musculoskeletal symptoms, individual factors and exposure to work constraints. In 2007, 2,332 responded to a follow-up questionnaire. The Nordic questionnaire was used both times to assess shoulder pain during the preceding 7 days. Associations between incident shoulder pain and individual and work-related factors at baseline were studied by multivariate logistic regression for both genders. RESULTS: A total of 946 men and 709 women without shoulder pain at baseline were eligible for the analyses. At follow-up, 105 men (11.1%) and 145 women (20.5%) reported shoulder pain. For men, age (OR 3.3, 95% CI, 1.7-6.5 for >=50 yr), working with arms above the shoulder (1.5; 1.0 2.3) and high perceived physical exertion (1.6; 1.0-2.5) increased the risk of incident shoulder pain. For women, the factors associated with incident shoulder pain were age (2.9; 1.5-5.8 for >=50 yr), obesity (2.5; 1.4-4.5), temporary employment (2.1; 1.1-3.7), high perceived physical exertion (2.2; 1.4-3.5) and low decision latitude (1.6; 1.0-2.3). CONCLUSION: Age was the strongest predictor of incident shoulder pain in both genders. BMI and biomechanical and psychosocial factors were also identified as risk factors, whereas no factor related to work organization remained in the final models. PMID- 22672885 TI - A Guillain-Barre syndrome-like neuropathy associated with arsenic exposure. AB - OBJECTIVES: We report on a patient presenting with an isolated polyneuropathy mimicking Guillain-Barre syndrome (GBS) associated with arsenic exposure. CASE: A 43-year-old man visited our emergency room complaining of progressive quadriparesis over the prior 5 days. His clinical course with laboratory data was typical of GBS. However, because of his recent use of herbal medication, we screened for the presence of several heavy metals. Serial analyses of urinary inorganic arsenic concentrations confirmed exposure to arsenic. He was diagnosed as arsenic neuropathy mimicking GBS without any systemic manifestation of arsenic intoxication. CONCLUSIONS: The present case study emphasizes the need to consider arsenic intoxication in patients presenting with acute demyelinating neuropathies and histories of herbal medication use. PMID- 22672886 TI - Early education and health outcomes of a 2001 U.S. birth cohort. AB - This paper looks at health outcomes, health behaviors, and health screening with respect to participation in Early Childhood Care and Education. With information on health status at multiple periods in time, we are able to look at whether healthier children select into early childhood education (as measured by center based preschool care and Head Start), as well as whether early childhood education has immediate and near-term effects on a range of health status measures. There is some evidence that child obesity is ameliorated by participation in center-based preschool or Head Start and this finding is supported by clear evidence of improved nutrition and increased levels of health screening. Effects on other health outcomes such as asthma, ear infections, and respiratory problems may be partially masked by unobserved heterogeneity. PMID- 22672887 TI - Intracranial melanocytic meningeal tumours and melanosis oculi: case report and literature review. AB - BACKGROUND: Melanocytic meningeal tumours are rare extra-axial neoplasms of the nervous system, with only three reported cases in the cavernous sinus. Herein we describe for the first time the association of ocular melanosis and multiple intracranial melanocytic meningeal tumours, with the presenting lesion being in the cavernous sinus. The importance of this association is discussed together with the diagnostic and therapeutic challenges of the case. CASE PRESENTATION: A 20-year-old man presented with a left sixth cranial nerve deficit; general examination documented only congenital melanosis of the homolateral eye. MRI examination showed a space occupying lesion in the left cavernous sinus, which was followed conservatively for 2 years, until a new space occupying lesion was evident at the level of the right frontal convexity: both lesions presented with neuroradiological characteristics suggestive of melanin content.The frontal convexity lesion was removed: intraoperatively the dura was markedly and diffusely melanotic. Histological examination documented a melanocytic meningeal tumour, with a proliferative index of 3 %. The patient underwent 3D-Conformal Radiation Therapy on the lesion of the cavernous sinus (total dose 5040 cGy), with initial tumour reduction. Three years later, due to a symptomatic growth, he underwent partial removal of the lesion in the cavernous sinus. Histological examination was unchanged. He then received adjuvant Temozolomide with Low Dose Fractionated Radiation Therapy (LD-FRT). Due to further disease progression cisplatin plus fotemustine were administered, concomitant with LD-FRT: after two cycles MRI documented significant disease regression. After a period of apparent disease control, the patient presented with persistent cough and evidence of multiple thoracic metastases, which lead to his death, seven years after presentation. CONCLUSIONS: Intracranial melanocytic meningeal tumours are challenging lesions, both from a diagnostic and therapeutic point of view; though rare, the possible association with ocular melanosis should be recognized and might facilitate an early diagnosis. Surgery remains the best possible option when feasible. In the event of partial resection, this "benign" disease might be clinically aggressive. PMID- 22672888 TI - Neuropeptidase activity is down-regulated by estradiol in steroid-sensitive regions of the hypothalamus in female mice. AB - Thimet oligopeptidase (TOP) and prolyl endopeptidase (PEP) are neuropeptidases involved in the hydrolysis of gonadotropin-releasing hormone, a key component of the hypothalamic-pituitary-gonadal axis. GnRH is regulated in part by feedback from steroid hormones such as estradiol. Previously, we demonstrated that TOP levels are down-regulated by estradiol in reproductively-relevant regions of the female rodent brain. The present study supports these findings by showing that TOP enzyme activity, as well as protein levels, in the ventromedial hypothalamic nucleus of female mice is controlled by estradiol. We further demonstrate that PEP levels in this same brain region are down-regulated by estradiol in parallel with those of TOP. These findings provide evidence that these neuropeptidases are part of the fine control of hormone levels in the HPG axis. PMID- 22672889 TI - Using Internet search engines to obtain medical information: a comparative study. AB - BACKGROUND: The Internet has become one of the most important means to obtain health and medical information. It is often the first step in checking for basic information about a disease and its treatment. The search results are often useful to general users. Various search engines such as Google, Yahoo!, Bing, and Ask.com can play an important role in obtaining medical information for both medical professionals and lay people. However, the usability and effectiveness of various search engines for medical information have not been comprehensively compared and evaluated. OBJECTIVE: To compare major Internet search engines in their usability of obtaining medical and health information. METHODS: We applied usability testing as a software engineering technique and a standard industry practice to compare the four major search engines (Google, Yahoo!, Bing, and Ask.com) in obtaining health and medical information. For this purpose, we searched the keyword breast cancer in Google, Yahoo!, Bing, and Ask.com and saved the results of the top 200 links from each search engine. We combined nonredundant links from the four search engines and gave them to volunteer users in an alphabetical order. The volunteer users evaluated the websites and scored each website from 0 to 10 (lowest to highest) based on the usefulness of the content relevant to breast cancer. A medical expert identified six well-known websites related to breast cancer in advance as standards. We also used five keywords associated with breast cancer defined in the latest release of Systematized Nomenclature of Medicine-Clinical Terms (SNOMED CT) and analyzed their occurrence in the websites. RESULTS: Each search engine provided rich information related to breast cancer in the search results. All six standard websites were among the top 30 in search results of all four search engines. Google had the best search validity (in terms of whether a website could be opened), followed by Bing, Ask.com, and Yahoo!. The search results highly overlapped between the search engines, and the overlap between any two search engines was about half or more. On the other hand, each search engine emphasized various types of content differently. In terms of user satisfaction analysis, volunteer users scored Bing the highest for its usefulness, followed by Yahoo!, Google, and Ask.com. CONCLUSIONS: Google, Yahoo!, Bing, and Ask.com are by and large effective search engines for helping lay users get health and medical information. Nevertheless, the current ranking methods have some pitfalls and there is room for improvement to help users get more accurate and useful information. We suggest that search engine users explore multiple search engines to search different types of health information and medical knowledge for their own needs and get a professional consultation if necessary. PMID- 22672892 TI - Comparative study on factors affecting anaerobic digestion of agricultural vegetal residues. AB - BACKGROUND: Presently, different studies are conducted related to the topic of biomass potential to generate through anaerobic fermentation process alternative fuels supposed to support the existing fossil fuel resources, which are more and more needed, in quantity, but also in quality of so called green energy. The present study focuses on depicting an optional way of capitalizing agricultural biomass residues using anaerobic fermentation in order to obtain biogas with satisfactory characteristics.. The research is based on wheat bran and a mix of damaged ground grains substrates for biogas production. RESULTS: The information and conclusions delivered offer results covering the general characteristics of biomass used , the process parameters with direct impact over the biogas production (temperature regime, pH values) and the daily biogas production for each batch relative to the used material. CONCLUSIONS: All conclusions are based on processing of monitoring process results , with accent on temperature and pH influence on the daily biogas production for the two batches. The main conclusion underlines the fact that the mixture batch produces a larger quantity of biogas, using approximately the same process conditions and input, in comparison to alone analyzed probes, indicating thus a higher potential for the biogas production than the wheat bran substrate.Adrian Eugen Cioabla, Ioana Ionel, Gabriela-Alina Dumitrel and Francisc Popescu contributed equally to this work. PMID- 22672894 TI - The dispersion of 137Cs in a shallow Mediterranean embayment (Saronikos Gulf- Elefsis Bay), estimated inventories and residence times. AB - The activity concentrations of (137)Cs in the water column of the Saronikos Gulf and Elefsis Bay (Greece) determined during four cruises between winter 2007 and winter 2009 are evaluated in the present study. The activity concentrations of (137)Cs ranged between 1.0 +/- 0.3 and 6.5 +/- 0.7 Bq m(-3) (mean: 2.7 +/- 1.6 Bq m(-3)), depending on sampling depth and season with a tendency to background levels. Regarding the vertical distribution of (137)Cs, maximum concentrations were observed in the interface between water and sediment during autumn and winter as a result of thermocline break-down at the end of winter that caused surface (137)Cs to sink into deeper layers. The mean surface residence time of the Chernobyl-derived (137)Cs in the Saronikos Gulf was estimated to be 15 +/- 4 y, whereas the effective and the ecological half-lives of (137)Cs in the study area were 6.2 +/- 1.5 and 7.8 +/- 1.9 y, respectively. Finally, the inventories of (137)Cs varied between 0.052 +/- 0.004 and 1.315 +/- 0.129 kBq m(-2) (mean: 0.355 +/- 0.302 kBq m(-2)), being in the lowest level comparing to the direct atmospheric deposition after the Chernobyl accident. PMID- 22672895 TI - Contamination mechanisms of air basin with tritium in venues of underground nuclear explosions at the former Semipalatinsk test site. AB - During the period of testing from 1945 to 1962 at the territory of Semipalatinsk test site (STS) within the Degelen Mountains in tunnels, 209 underground nuclear explosions were produced. Many of the tunnels have seasonal water seepage in the form of streams, through which tritium migrates from the underground nuclear explosion (UNE) venues towards the surface. The issue of tritium contamination occupies a special place in the radioactive contamination of the environment. In this paper we assess the level and distribution of tritium in the atmospheric air of ecosystems with water seepage at tunnels No 176 and No 177, located on "Degelen" site. There has been presented general nature of tritium distribution in the atmosphere relative to surface of a watercourse which has been contaminated with tritium. The basic mechanisms were studied for tritium distribution in the air of studied ecosystems, namely, the distribution of tritium in the systems: water-atmosphere, tunnel air-atmosphere, soil water atmosphere, vegetation-atmosphere. An analytical calculation of tritium concentration in the atmosphere by the concentration of tritium in water has been performed. There has experimentally obtained the dependence for predictive assessment of tritium concentrations in air as a function of tritium concentration in one of the inlet sources such as water, tunnel air, soil water, vegetation, etc.. The paper also describes the general nature of tritium distribution in the air in the area "Degelen". PMID- 22672896 TI - Effective marker placement for functional identification of the centre of rotation at the hip. AB - The accuracy and precision of quantifying musculoskeletal kinematics, and particularly determining the centre of rotation (CoR) at the hip joint, using skin marker based motion analysis is limited by soft tissue artefact (STA). We posed the question of whether the contribution of individual markers towards improving the precision of the functional joint centre using marker based methods could be assessed, and then utilised to allow effective marker placement for determination of the CoR at the hip. Sixty-three retro-reflective skin markers were placed to encompass the thighs of seven healthy subjects, together with a set of sixteen markers on the pelvis. The weighted optimal common shape technique (wOCST) was then applied to determine the weighting, or importance, of each marker for identifying the centre of rotation at the hip. The markers with the highest weightings over all subjects and measurements were determined that identified the HJC with the highest precision. The use of six markers in selected regions (two anterior, two lateral and two posterior) allowed the HJC to be determined with a similar precision to the complete set of 63 markers, with the determined regions predominantly distant from the hip joint, excluding areas associated with the bellies of large muscles and therefore large motion artefact from muscle activity. The novel approach presented here allows an understanding of each marker's contribution towards a precise joint determination, and therefore enables the targeted placement of markers for reliable assessment of musculoskeletal kinematics. PMID- 22672898 TI - Further validation of a Chinese version of the Obsessive-Compulsive Inventory Revised. AB - BACKGROUND: There has been an increased effort to understand the nature of obsessive-compulsive disorder (OCD) in non-Western cultures. In particular, growing research has examined OCD in China, but there are no comprehensive instruments that measure both OCD severity and heterogeneity for characterizing samples. AIMS: A validated, comprehensive measure that could be used in China would provide researchers with a useful instrument for evaluating severity and heterogeneity of OCD in a non-Western culture, allowing researchers to better understand the universal and cultural components that play a role in the nature of OCD. METHOD: The current investigation presents data on the reliability and validity of a Mandarin translation of the Obsessive-Compulsive Inventory-Revised (CH-OCI) using both a student (n = 1950) and clinical sample (n = 50 patients with OCD; n = 50 patients with anxiety as a comparison group). RESULTS: Results support the factor structure, convergent and discriminant validity, criterion related validity, test-retest reliability, and internal consistency of the CH OCI. CONCLUSIONS: Validation of the instrument permits researchers and clinicians to measure OCD presentation in Mandarin-speaking samples. PMID- 22672897 TI - Potential utility of eGFP-expressing NOG mice (NOG-EGFP) as a high purity cancer sampling system. AB - PURPOSE: It is still technically difficult to collect high purity cancer cells from tumor tissues, which contain noncancerous cells. We hypothesized that xenograft models of NOG mice expressing enhanced green fluorescent protein (eGFP), referred to as NOG-EGFP mice, may be useful for obtaining such high purity cancer cells for detailed molecular and cellular analyses. METHODS: Pancreato-biliary cancer cell lines were implanted subcutaneously to compare the tumorigenicity between NOG-EGFP mice and nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. To obtain high purity cancer cells, the subcutaneous tumors were harvested from the mice and enzymatically dissociated into single-cell suspensions. Then, the cells were sorted by fluorescence activated cell sorting (FACS) for separation of the host cells and the cancer cells. Thereafter, the contamination rate of host cells in collected cancer cells was quantified by using FACS analysis. The viability of cancer cells after FACS sorting was evaluated by cell culture and subsequent subcutaneous reimplantation in NOG-EGFP mice. RESULTS: The tumorigenicity of NOG-EGFP mice was significantly better than that of NOD/SCID mice in all of the analyzed cell lines (p < 0.01). Sorting procedures enabled an almost pure collection of cancer cells with only slight contamination by host cells. Reimplantation of the sorted cancer cells formed tumors again, which demonstrated that cell viability after sorting was well maintained. CONCLUSIONS: This method provides a novel cancer sampling system for molecular and cellular analysis with high accuracy and should contribute to the development of personalized medicine. PMID- 22672899 TI - Upregulation of calprotectin and downregulation of retinol binding protein in the serum of workers with trichloroethylene-induced hypersensitivity dermatitis. AB - OBJECTIVES: The aim of this study was to explore the involved pathophysiological processes and develop biomarkers of trichloroethylene-induced hypersensitivity dermatitis (THD). METHODS: We examined the impact of THD on the serum proteome in 8 male patients by comparing the serum samples between acute and healed stages. Sample pooling and immunodepletion were applied for sample preparation. Two dimensional gel electrophoresis coupled with matrix-assisted laser-desorption ionization time-of-flight mass spectrometry (MALDI-TOF-TOF/MS) was utilized to identify and quantitate differentially expressed proteins. Changes in selected proteins were further confirmed by an ELISA assay. RESULTS: A total of 41 spots were quantitated with significant alteration (p<0.05; fold-change>=+/- 3.0) in the serum between the acute and healed stages. Of these proteins, 26 proteins were identified by MALDI-TOF-TOF/MS. The identified proteins could be categorized into diverse functional classes, e.g., immunity and defense response, vitamin and lipid transport, fatty acid biosynthesis, actin binding, proteolysis and glycolysis. The ELISA assay confirmed the relative upregulation of calprotectin (S100A8/A9) and downregulation of retinol binding protein (RBP4) in the serum of the acute stage. The alteration of calprotectin and RBP4 was found to be specific to THD rather than trichloroethylene exposure. CONCLUSIONS: The pathophysiological processes underlying THD may involve elevated inflammatory responses and oxidative stress, inhibition of vitamin transport, depression of fatty acid biosynthesis, loss of extracellular actin scavenger, increase in oxygen transport, dysfunction in lipid transport, proteolysis and glycolysis. The combination of higher calprotectin and lower RBP4 levels in the serum could be used as potential biomarkers of THD. PMID- 22672900 TI - Transforming growth factor-beta suppresses metastasis in a subset of human colon carcinoma cells. AB - BACKGROUND: TGFbeta signaling has typically been associated with suppression of tumor initiation while the role it plays in metastasis is generally associated with progression of malignancy. However, we present evidence here for an anti metastatic role of TGFbeta signaling. METHODS: To test the importance of TGFbeta signaling to cell survival and metastasis we compared human colon carcinoma cell lines that are either non-tumorigenic with TGFbeta response (FET), or tumorigenic with TGFbeta response (FETalpha) or tumorigenic with abrogated TGFbeta response via introduction of dominant negative TGFbetaRII (FETalpha/DN) and their ability to metastasize. Metastatic competency was assessed by orthotopic transplantation. Metastatic colony formation was assessed histologically and by imaging. RESULTS: Abrogation of TGFbeta signaling through introduction of a dominant negative TGFbeta receptor II (TGFbetaRII) in non-metastatic FETalpha human colon cancer cells permits metastasis to distal organs, but importantly does not reduce invasive behavior at the primary site. Loss of TGFbeta signaling in FETalpha-DN cells generated enhanced cell survival capabilities in response to cellular stress in vitro. We show that enhanced cellular survival is associated with increased AKT phosphorylation and cytoplasmic expression of inhibitor of apoptosis (IAP) family members (survivin and XIAP) that elicit a cytoprotective effect through inhibition of caspases in response to stress. To confirm that TGFbeta signaling is a metastasis suppressor, we rescued TGFbeta signaling in CBS metastatic colon cancer cells that had lost TGFbeta receptor expression due to epigenetic repression. Restoration of TGFbeta signaling resulted in the inhibition of metastatic colony formation in distal organs by these cells. These results indicate that TGFbeta signaling has an important role in the suppression of metastatic potential in tumors that have already progressed to the stage of an invasive carcinoma. CONCLUSIONS: The observations presented here indicate a metastasis suppressor role for TGFbeta signaling in human colon cancer cells. This raises the concern that therapies targeting inhibition of TGFbeta signaling may be imprudent in some patient populations with residual TGFbeta tumor suppressor activity. PMID- 22672901 TI - Human Fidgetin is a microtubule severing the enzyme and minus-end depolymerase that regulates mitosis. AB - Fidgetin is a member of the AAA protein superfamily with important roles in mammalian development. Here we show that human Fidgetin is a potent microtubule severing and depolymerizing the enzyme used to regulate mitotic spindle architecture, dynamics and anaphase A. In vitro, recombinant human Fidgetin severs taxol-stabilized microtubules along their length and promotes depolymerization, primarily from their minus-ends. In cells, human Fidgetin targets to centrosomes, and its depletion with siRNA significantly reduces the velocity of poleward tubulin flux and anaphase A chromatid-to-pole motion. In addition, the loss of Fidgetin induces a microtubule-dependent enlargement of mitotic centrosomes and an increase in the number and length of astral microtubules. Based on these data, we propose that human Fidgetin actively suppresses microtubule growth from and attachment to centrosomes. PMID- 22672902 TI - Suppression of replicative senescence by rapamycin in rodent embryonic cells. AB - The TOR (target of rapamycin) pathway is involved in aging in diverse organisms from yeast to mammals. We have previously demonstrated in human and rodent cells that mTOR converts stress-induced cell cycle arrest to irreversible senescence (geroconversion), whereas rapamycin decelerates or suppresses geroconversion during cell cycle arrest. Here, we investigated whether rapamycin can suppress replicative senescence of rodent cells. Mouse embryonic fibroblasts (MEFs) gradually acquired senescent morphology and ceased proliferation. Rapamycin decreased cellular hypertrophy, and SA-beta-Gal staining otherwise developed by 4 6 passages, but it blocked cell proliferation, masking its effects on replicative lifespan. We determined that rapamycin inhibited pS6 at 100-300 pM and inhibited proliferation with IC(50) around 30 pM. At 30 pM, rapamycin partially suppressed senescence. However, the gerosuppressive effect was balanced by the cytostatic effect, making it difficult to suppress senescence without causing quiescence. We also investigated rat embryonic fibroblasts (REFs), which exhibited markers of senescence at passage 7, yet were able to slowly proliferate until 12-14 passages. REFs grew in size, acquired a large, flat cell morphology, SA-beta-Gal staining and components of DNA damage response (DDR), in particular, gammaH2AX/53BP1 foci. Incubation of REFs with rapamycin (from passage 7 to passage 10) allowed REFs to overcome the replicative senescence crisis. Following rapamycin treatment and removal, a fraction of proliferating REFs gradually increased and senescent phenotype disappeared completely by passage 24. PMID- 22672903 TI - A role for CDK9 in UV damage response. PMID- 22672904 TI - Repression of endometrial tumor growth by targeting SREBP1 and lipogenesis. AB - The aberrantly increased lipogenesis is a universal metabolic feature of proliferating tumor cells. Although most normal cells acquire the bulk of their fatty acids from circulation, tumor cells synthesize more than 90% of required lipids de novo. The sterol regulatory element-binding protein 1 (SREBP1), encoded by SREBF1 gene, is a master regulator of lipogenic gene expression. SREBP1 and its target genes are overexpressed in a variety of cancers; however, the role of SREBP1 in endometrial cancer is largely unknown. We have screened a cohort of endometrial cancer (EC) specimen for their lipogenic gene expression and observed a significant increase of SREBP1 target gene expression in cancer cells compared with normal endometrium. By using immunohistochemical staining, we confirmed SREBP1 protein overexpression and demonstrated increased nuclear distribution of SREBP1 in EC. In addition, we found that knockdown of SREBP1 expression in EC cells suppressed cell growth, reduced colonigenic capacity and slowed tumor growth in vivo. Furthermore, we observed that knockdown of SREBP1 induced significant cell death in cultured EC cells. Taken together, our results show that SREBP1 is essential for EC cell growth both in vitro and in vivo, suggesting that SREBP1 activity may be a novel therapeutic target for endometrial cancers. PMID- 22672907 TI - Induction of ASAP (MAP9) contributes to p53 stabilization in response to DNA damage. AB - p53 is a key tumor suppressor that controls DNA damage response and genomic integrity. In response to genotoxic stress, p53 is stabilized and activated, resulting in controlled activation of genes involved in cell cycle arrest, DNA repair and/or apoptosis. ASAP is a centrosome- and spindle-associated protein, the deregulation of which induces severe mitotic defects. We show here that following double-strand break DNA formation, ASAP directly interacts with and stabilizes p53 by enhancing its p300-mediated acetylation and blocking its MDM2 mediated ubiquitination and degradation, leading to an increase of p53 transcriptional activity. Upon DNA damage, ASAP is transiently accumulated before being degraded upon persistent damage. This work links the p53 response with the cytoskeleton and confirms that the DNA-damaging signaling pathway is coordinated by centrosomal proteins. We reveal the existence of a new pathway through which ASAP signals the DNA damage response by regulating the p300-MDM2-p53 loop. These results point out ASAP as a possible target for the design of drugs to sensitize radio-resistant tumors. PMID- 22672905 TI - Global tumor protein p53/p63 interactome: making a case for cisplatin chemoresistance. AB - Cisplatin chemoresistance is a clinical problem that leads to treatment failure in various human epithelial cancers. Members of tumor protein (TP) p53 family play various critical roles in the multiple molecular mechanisms underlying the chemoresistance of tumor cells. However, the in-depth mechanisms of the cellular response to cisplatin-induced cell death are still under thorough investigation. We previously showed that squamous cell carcinoma (SCC) cells exposed to cisplatin display an ATM-dependent phosphorylation of DeltaNp63alpha, leading to a specific function of the phosphorylated (p)-DeltaNp63alpha transcription factor in cisplatin-sensitive tumor cells. We further found that SCC cells expressing non-p-DeltaNp63alpha-S385G became cisplatin-resistant. Using quantitative mass spectrometry of protein complexes labeled with isobaric tags, we showed that TP53 and DeltaNp63alpha are involved in numerous protein-protein interactions, which are likely to be implicated in the response of tumor cells to cisplatin exposure. We found that p-DeltaNp63alpha binds to the splicing complex, leading to repression of mRNA splicing and activation of ACIN1-mediated cell death pathway. In contrast to p-DeltaNp63alpha, non-p-DeltaNp63alpha fails to bind the critical members of the splicing complex, thereby leading to activation of RNA splicing and reduction of cell death pathway. Overall, our studies provide an integrated proteomic platform in making a case for the role of the p53/p63 interactome in cisplatin chemoresistance. PMID- 22672906 TI - Timeless preserves telomere length by promoting efficient DNA replication through human telomeres. AB - A variety of telomere protection programs are utilized to preserve telomere structure. However, the complex nature of telomere maintenance remains elusive. The Timeless protein associates with the replication fork and is thought to support efficient progression of the replication fork through natural impediments, including replication fork block sites. However, the mechanism by which Timeless regulates such genomic regions is not understood. Here, we report the role of Timeless in telomere length maintenance. We demonstrate that Timeless depletion leads to telomere shortening in human cells. This length maintenance is independent of telomerase, and Timeless depletion causes increased levels of DNA damage, leading to telomere aberrations. We also show that Timeless is associated with Shelterin components TRF1 and TRF2. Timeless depletion slows telomere replication in vitro, and Timeless-depleted cells fail to maintain TRF1-mediated accumulation of replisome components at telomeric regions. Furthermore, telomere replication undergoes a dramatic delay in Timeless-depleted cells. These results suggest that Timeless functions together with TRF1 to prevent fork collapse at telomere repeat DNA and ensure stable maintenance of telomere length and integrity. PMID- 22672908 TI - Cancers co-opt cohabitants' catabolism: autophagy and senescence in the tumor stroma. PMID- 22672909 TI - Heightened cough response to bronchoconstriction in cough variant asthma. AB - BACKGROUND AND OBJECTIVE: The pathophysiology of cough variant asthma (CVA) is poorly understood. We compared bronchoconstriction-triggered cough between CVA patients and normal control (NC) subjects. METHODS: There were two protocols in the study. We measured bronchial responsiveness to methacholine (MCh) and counted the number of coughs in nine CVA patients and seven NC subjects (study A). Using partial and full flow-volume curves, expiratory flow of the partial flow-volume curve at 40% above residual volume level (PEF40) and FEV(1) were used to measure bronchoconstriction. Mild bronchoconstriction was defined as a 35% fall in PEF40 (PC(35) -PEF40), and more severe bronchoconstriction as a 20% fall in FEV1 (PC20) -FEV(1) ). In study B, the same measurements were obtained in six CVA patients before and after therapy. RESULTS: In study A, more coughs were provoked at PC35 PEF40 in CVA patients (median, 60 coughs/32 min post challenge; range, 12-135) than in NC subjects (median, 0/32 min; range, 0-13; P < 0.05). At PC20 -FEV1 , more coughs were provoked in CVA patients (median, 60/32 min; range, 12-150) than in NC subjects (median, 20/32 min; range, 0-54; P < 0.05). In study B, the six CVA patients who underwent re-examination after treatment had less coughs at PC35 -PEF40 (median, 3/32 min; range, 0-14) and PC(20) -FEV1 (median, 13/32 min; range, 3-26) after therapy than before therapy (median, 54/32 min; range, 33-125 and 52/32 min, 45-96, respectively; P < 0.05). CONCLUSIONS: We identified heightened cough response to bronchoconstriction as a feature of CVA. PMID- 22672910 TI - The ParA/MinD family puts things in their place. AB - Bacteria must segregate their DNA and position a septum to grow and divide. In many bacteria, MinD is involved in spatial regulation of the cytokinetic Z ring, and ParAs are involved in chromosome and plasmid segregation. The use of the MinD/ParA family to provide positional information for spatial organization continues to expand with the recognition that orphan ParAs are required for segregating cytoplasmic protein clusters and the polar localization of chemotaxis proteins, conjugative transfer machinery, type IV pili, and cellulose synthesis. Also, some bacteria lacking MinD use orphan ParAs to regulate cell division. Positioning of MinD/ParA proteins is either due to self-organization on a surface or reliance on a landmark protein that functions as a molecular beacon. PMID- 22672911 TI - Intestinal microbiota is a plastic factor responding to environmental changes. AB - Traditionally regarded as stable through the entire lifespan, the intestinal microbiota has now emerged as an extremely plastic entity, capable of being reconfigured in response to different environmental factors. In a mutualistic context, these microbiome fluctuations allow the host to rapidly adjust its metabolic and immunologic performances in response to environmental changes. Several circumstances can disturb this homeostatic equilibrium, inducing the intestinal microbiota to shift from a mutualistic configuration to a disease associated profile. A mechanistic comprehension of the dynamics involved in this process is needed to deal more rationally with the role of the human intestinal microbiota in health and disease. PMID- 22672912 TI - Potential role of multiple carbon fixation pathways during lipid accumulation in Phaeodactylum tricornutum. AB - BACKGROUND: Phaeodactylum tricornutum is a unicellular diatom in the class Bacillariophyceae. The full genome has been sequenced (<30 Mb), and approximately 20 to 30% triacylglyceride (TAG) accumulation on a dry cell basis has been reported under different growth conditions. To elucidate P. tricornutum gene expression profiles during nutrient-deprivation and lipid-accumulation, cell cultures were grown with a nitrate to phosphate ratio of 20:1 (N:P) and whole genome transcripts were monitored over time via RNA-sequence determination. RESULTS: The specific Nile Red (NR) fluorescence (NR fluorescence per cell) increased over time; however, the increase in NR fluorescence was initiated before external nitrate was completely exhausted. Exogenous phosphate was depleted before nitrate, and these results indicated that the depletion of exogenous phosphate might be an early trigger for lipid accumulation that is magnified upon nitrate depletion. As expected, many of the genes associated with nitrate and phosphate utilization were up-expressed. The diatom-specific cyclins cyc7 and cyc10 were down-expressed during the nutrient-deplete state, and cyclin B1 was up-expressed during lipid-accumulation after growth cessation. While many of the genes associated with the C3 pathway for photosynthetic carbon reduction were not significantly altered, genes involved in a putative C4 pathway for photosynthetic carbon assimilation were up-expressed as the cells depleted nitrate, phosphate, and exogenous dissolved inorganic carbon (DIC) levels. P. tricornutum has multiple, putative carbonic anhydrases, but only two were significantly up-expressed (2-fold and 4-fold) at the last time point when exogenous DIC levels had increased after the cessation of growth. Alternative pathways that could utilize HCO3- were also suggested by the gene expression profiles (e.g., putative propionyl-CoA and methylmalonyl-CoA decarboxylases). CONCLUSIONS: The results indicate that P. tricornutum continued carbon dioxide reduction when population growth was arrested and different carbon-concentrating mechanisms were used dependent upon exogenous DIC levels. Based upon overall low gene expression levels for fatty acid synthesis, the results also suggest that the build-up of precursors to the acetyl-CoA carboxylases may play a more significant role in TAG synthesis rather than the actual enzyme levels of acetyl CoA carboxylases per se. The presented insights into the types and timing of cellular responses to inorganic carbon will help maximize photoautotrophic carbon flow to lipid accumulation. PMID- 22672913 TI - Asia Cohort Consortium: challenges for collaborative research. AB - In this era of chronic diseases, large studies are essential in investigating genes, environment, and gene-environment interactions as disease causes, particularly when associations are important but not strong. Moreover, to allow expansion and generalization of the results, studies should be conducted in populations outside Western countries. Here, we briefly describe the Asia Cohort Consortium (ACC), a collaborative cancer cohort research project that was first proposed in 2004 and now involves more than 1 million healthy individuals across Asia. There are approximately 50 active members from Bangladesh, China, India, Japan, Korea, Malaysia, Singapore, Taiwan, Thailand, the United States, and elsewhere. To date, the work of the ACC includes 3 articles published in 2011 on the roles of body mass index, tobacco smoking, and alcohol consumption in mortality, diabetes, and cancer of the small intestine. Many challenges remain, including data harmonization, resolution of ethical and legal issues, establishment of protocols for biologic samples and transfer agreements, and funding procurement. PMID- 22672914 TI - BMI is strongly associated with hypertension, and waist circumference is strongly associated with type 2 diabetes and dyslipidemia, in northern Chinese adults. AB - BACKGROUND: Obesity is closely associated with chronic diseases such as hypertension, type 2 diabetes mellitus (T2DM), and dyslipidemia. We analyzed the optimal obesity index cut-off values for metabolic syndrome (MetS), and identified the obesity index that is more closely associated with these chronic diseases, in a population of northern Chinese. METHODS: We surveyed 8940 adults (age, 20-74 years) living in northern China for chronic diseases. Receiver operating characteristics (ROC) analysis, relative risk, and multivariate regression were used to develop an appropriate index and optimal cut-off values for MetS and obesity-related chronic diseases. RESULTS: Waist circumference (WC) and body mass index (BMI) were good markers for MetS, WC was a good marker for T2DM and dyslipidemia, and BMI was a good marker for hypertension. The optimal BMI cut-off value of MetS was 24 kg/m2, and the optimal WC cut-offs were 86 cm and 78 cm in men and women, respectively. Relative risk regression models showed that BMI was associated with hypertension, T2DM, and hypertriglyceridemia and a higher prevalence ratio (PR) for hypertension: 2.35 (95% CI, 2.18-2.50). WC was associated with T2DM, hypertension, and hypertriglyceridemia, with PRs of 2.05 (1.63-2.55) for T2DM and 2.47 (2.04-2.85) for hypertriglyceridemia. In multivariate regression models, the standardized regression coefficients (SRCs) of BMI were greater for SBP and DBP, and the SRC of WC was greater for fasting blood glucose, 2-hour postload blood glucose, triglyceride, and total cholesterol. CONCLUSIONS: Our analysis of a population of northern Chinese indicates that the optimal cut-off values for MetS are WCs of 86 cm in men and 78 cm in women and a BMI of 24 kg/m2 in both sexes. BMI was strongly associated with hypertension, while WC was strongly associated with T2DM and dyslipidemia. PMID- 22672915 TI - The effect of virtual reality gaming on dynamic balance in older adults. AB - BACKGROUND: physical therapy interventions that increase functional strength and balance have been shown to reduce falls in older adults. AIM: this study compared a virtual reality group (VRG) and a control group (CG). DESIGN: randomised controlled 6-week intervention with pre- and post-test evaluations. SETTING: outpatient geriatric orthopaedic and balance physical therapy clinic. POPULATION: forty participants were randomised into two groups. METHOD: the VRG received three different Nintendo(r) Wii FIT balance interventions three times per week for 6 weeks and the CG received no intervention. RESULTS: compared with the CG, post-intervention measurements showed significant improvements for the VRG in the 8-foot Up & Go test [median decrease of 1.0 versus -0.2 s, (P=0.038) and the Activities-specific Balance Confidence Scale (6.9 versus 1.3%) (P=0.038)]. CONCLUSION: virtual reality gaming provides clinicians with a useful tool for improving dynamic balance and balance confidence in older adults. PMID- 22672916 TI - Identification of cancer-related symptom clusters: an empirical comparison of exploratory factor analysis methods. AB - CONTEXT: Symptom clusters, important for symptom management strategies, have been determined empirically by various analytical methods. Guidance to select methods from the options available in standard statistical packages is limited. OBJECTIVES: To compare alternative common factor analysis (FA) extraction methods appropriate to the data, to assess whether or not they determine similar symptom clusters, and to propose analytical approaches that are useful in this clinical context. METHODS: Within one month of commencing chemotherapy, outpatients from oncology and hematology clinics (n = 202) reported their symptom experience on a modified Rotterdam Symptom Checklist. Symptom distress levels in the past week were rated on a scale of one (not at all) to four (very much). In a secondary data analysis of 42 symptoms, the associations between symptoms and factors were determined using alternative common FA methods: principal axis factoring, unweighted least squares, image factor analysis, and alpha factor analysis (AFA). Symptom inclusion in a cluster was based on the interpretation of pattern and structure coefficients, and importantly, clinical relevance of the grouping. RESULTS: Five symptom clusters were commonly identified across methods: musculoskeletal discomforts/lethargy, oral discomforts, upper gastrointestinal discomforts, vasomotor symptoms, and gastrointestinal toxicities. In AFA, three additional clusters were lethargy, somatic symptoms, and treatment-related symptom clusters. CONCLUSION: The most parsimonious solution resulted from principal axis factoring, but for large numbers of symptoms, AFA may be superior by identifying symptom clusters more useful for symptom management. Interpreting complex symptom relationships may lead to the investigation of pathophysiological mechanisms and intervention opportunities. Future studies should include psychological and cognitive symptoms. PMID- 22672917 TI - A pilot randomized controlled trial of an oral care intervention to reduce mucositis severity in stem cell transplant patients. AB - CONTEXT: Oral mucositis remains a significant problem in autologous stem cell transplantation (ASCT). OBJECTIVES: This pilot trial assessed the effectiveness of oral cryotherapy plus an oral care protocol in reducing oral mucositis severity in ASCT patients. METHODS: Patients admitted for ASCT were randomly allocated to either the experimental arm (n=23) or usual care (n=23). All participants received information on principles of good oral hygiene and skills training in oral self-care. Patients in the experimental arm had a 60-minute regimen of oral cryotherapy. The primary outcome of oral mucositis severity and secondary outcomes of mucositis-related pain and functional intake of food and fluids were measured at Days -1, 3, 6, 9, and 12. Length of hospital stay was determined by counting backward from discharge day to admission. Perception of tolerability and acceptability of the 60-minute cryotherapy and frequency of the oral care regimen also were assessed. RESULTS: Forty-eight patients were recruited at the study site in six months. The overall mean (SE) of oral mucositis severity for the experimental arm was significantly lower than that for the control group: 0.43 (0.12) vs. 1.14 (0.12); P<0.001, on a 0-4 scale. The overall mean (SE) mucositis-related pain score for the experimental arm also was significantly lower than that for the control group: 0.30 (0.23) vs. 1.64 (0.24); P<0.001, on a 0-10 scale. CONCLUSION: Oral cryotherapy plus an oral care protocol appears to be beneficial in reducing severity of mucositis compared with an oral care protocol alone. PMID- 22672918 TI - Attitudes of health care professionals to opioid prescribing in end-of-life care: a qualitative focus group study. AB - CONTEXT: Opioid therapy is central to the management of pain in the field of generalist palliative and end-of-life care, and international guidelines highlight the need for opioids to be used as part of a comprehensive strategy to treat pain. However, evidence suggests that the use of opioids in palliative care is suboptimal, and many patients do not receive adequate pain control at the end of life. OBJECTIVES: This study aimed to explore the attitudes of health care professionals to opioid prescribing in generalist end-of-life care. METHODS: Thirty-one health and allied health professionals participated in four focus groups. Two focus groups took place in general practitioner practices and two in hospices. RESULTS: Findings revealed that significant barriers exist to the appropriate use of opioids in end-of-life care. Particular barriers exist for professionals working in primary care and include concerns about giving high doses and having insufficient training in opioid use. Working partnerships between specialist and generalist palliative care providers are important for increasing generalist confidence in prescribing. Patients and their families often have concerns about initiating opioids, and specialist nursing staff are crucial to managing and alleviating these concerns. CONCLUSION: Significant barriers exist to the appropriate use of opioids in end-of-life care. If international priorities on improving pain management at the end of life are to be achieved, educational opportunities for generalists need to be enhanced, and effective interprofessional working models need to be developed so that pain management for patients at the end of life is optimized. PMID- 22672919 TI - Guided imagery for non-musculoskeletal pain: a systematic review of randomized clinical trials. AB - CONTEXT: Our previous review of the literature concluded that there is encouraging evidence that guided imagery alleviates musculoskeletal pain, but the value of guided imagery in the management of non-musculoskeletal pain remains uncertain. OBJECTIVES: The objective of this systematic review was to assess the effectiveness of guided imagery as a treatment option for non-musculoskeletal pain. METHODS: Six databases were searched from their inception to February 2011. Randomized clinical trials were considered if they investigated guided imagery in human patients with any type of non-musculoskeletal pain in any anatomical location and assessed pain as a primary outcome measure. Trials of motor imagery and hypnosis were excluded. The selection of studies, data extraction, and validation were performed independently by two reviewers. RESULTS: Fifteen randomized clinical trials met the inclusion criteria. Their methodological quality was generally poor. Eleven trials found that guided imagery led to a significant reduction of non-musculoskeletal pain. Four studies found no change in non-musculoskeletal pain with guided imagery in comparison with progressive relaxation, standard care, or no treatment. CONCLUSION: The evidence that guided imagery alleviates non-musculoskeletal pain is encouraging but remains inconclusive. PMID- 22672920 TI - An exploratory study to clarify the cluster of symptoms predictive of chemotherapy-related nausea using random forest modeling. AB - CONTEXT: Chemotherapy-related nausea is experienced by most cancer patients receiving chemotherapy. Although vomiting is managed well with current antiemetics, nausea is difficult to manage and little is understood about its development. OBJECTIVES: The aim was to determine whether nausea exists as part of a symptom cluster and evaluate the symptom cluster's impact on patients' quality of life, psychological distress, and nutritional status. METHODS: A prospective observational design over two cycles of chemotherapy was used. Patients completed the Memorial Symptom Assessment Scale, Hospital Anxiety and Depression Scale, Functional Assessment of Cancer Therapy-General, and Patient Generated Subjective Global Assessment before chemotherapy and at the end of the first and second cycles of treatment. Random forest modeling, a state-of-the-art prediction method, was used to analyze the data. RESULTS: One hundred four patients participated in the study. Nausea was found to be a dynamic experience, changing over time. "Core" symptoms, predictive of the presence of nausea, were identified and included appetite loss, feeling bloated, vomiting, taste changes, and lack of energy. Although nausea alone did have an impact on patient outcomes, the impact was significantly higher in relation to physical and functional quality of life and nutritional status in those patients who had more than two symptoms from the nausea cluster. CONCLUSION: This exploratory study, using an innovative analytical approach, has shown that nausea is a complex symptom affected by the presence and/or severity of other concurrent symptoms (the symptom cluster). The findings have implications for the measurement of nausea and also to target people for interventions to manage nausea and its cluster of symptoms. PMID- 22672921 TI - Culture is a priority for research in end-of-life care in Europe: a research agenda. AB - CONTEXT: Culture has a profound influence on our understanding of what is appropriate care for patients at the end of life (EoL), but the evidence base is largely nonexistent. OBJECTIVES: An international workshop was organized to compile a research agenda for cultural issues in EoL research, and assess challenges and implications of the integration of the culture concept in different contexts. METHODS: Participant experts were identified from the expert network established through an Internet-based call for expertise on culture and EoL care and from meetings. The workshop comprised presentations of research priorities from country and disciplinary perspectives, and group discussions. Analysis used all data gathered in the workshop and applied standard qualitative techniques. RESULTS: Thirty experts participated in the workshop and identified the following priorities for cross-cultural research: 1) clarifying the concepts of culture and cultural competence; 2) defining EoL in a context of social and cultural diversity, with a focus on concepts of EoL care and bioethics, experiences of receiving and giving EoL care, and care practices in different settings; and 3) developing appropriate methodologies and outcome measurements that address diversity. CONCLUSION: This first pan-European meeting compiled a research agenda, identifying key areas for future research focusing on culture, diversity, and their operationalization. This requires international and multidisciplinary collaboration, which is necessary in the current efforts to synthesize best practices in EoL care. PMID- 22672922 TI - Considerations in developing and delivering a nonpharmacological intervention for symptom management in lung cancer: the views of patients and informal caregivers. AB - CONTEXT: Few studies consider patient's and caregiver's preferences when developing nonpharmacological interventions. This is important to develop acceptable and accessible nonpharmacological interventions for patients with cancer. OBJECTIVES: The objective of this study was to identify the views of patients with lung cancer and their informal caregivers on the desirable components of a novel nonpharmacological intervention for the management of the symptom cluster of cough, breathlessness, and fatigue, and their needs and preferences regarding uptake and delivery of the intervention. METHODS: This study was qualitative in orientation, using semistructured interviews and framework analysis to elicit the views of 37 patients with lung cancer and 23 caregivers regarding the issues that were perceived to be important regarding the development and delivery of a nonpharmacological intervention. RESULTS: A number of key issues were identified that carried important implications for patient participation and adherence to the intervention, including the perceived relevance of potential techniques; appreciable benefits in the short term; convenience; variation in patient preferences; timing of the intervention; venue; caregiver involvement; the provider of the intervention, and contact with other patients. CONCLUSION: The data from this study have provided insight into the key issues that are likely to influence the development, uptake, and delivery of a nonpharmacological intervention to help manage the respiratory symptom cluster of cough, breathlessness, and fatigue. It is crucial that these findings are considered when developing and modeling a nonpharmacological symptom management intervention. PMID- 22672923 TI - The association between dairy food intake and the incidence of diabetes in Australia: the Australian Diabetes Obesity and Lifestyle Study (AusDiab). AB - OBJECTIVE: Several studies have suggested that dairy food may reduce the risk of obesity and metabolic abnormalities but few have been able to conclusively demonstrate that it reduces the risk of diabetes. The aim of the present analysis was to investigate if dairy food intake independently reduces the risk of diabetes. DESIGN: The Australian Diabetes Obesity and Lifestyle Study (AusDiab) is a national, population-based, prospective survey conducted over 5 years. Baseline measurements included a 121-item FFQ, anthropometrics and an oral glucose tolerance test. SETTING: Forty-two randomly selected clusters across Australia. SUBJECTS: Adults aged >=25 years who participated in the baseline survey and returned to follow-up 5 years later. RESULTS: A total of 5582 participants with complete data were eligible for analysis, 209 of whom had incident diabetes. Compared with men in the first tertile of dairy food intake, men in the third tertile had a significantly reduced risk of developing diabetes after adjustment for age, sex, total energy intake, family history of diabetes, education, physical activity, smoking status, fasting serum TAG and HDL cholesterol, systolic blood pressure, waist circumference and hip circumference (OR = 0.53, 95 % CI 0.29, 0.96; P = 0.033). A similar non-significant association was observed in women. CONCLUSIONS: Dietary patterns that incorporate high intakes of dairy food may reduce the risk of diabetes among men. Further investigation into the relationship between dairy food intake and diabetes needs to be undertaken to fully understand the potential mechanism of this observation. PMID- 22672924 TI - Polymorphisms of the drug transporter gene ABCB1 predict side effects of treatment with cabergoline in patients with PRL adenomas. AB - INTRODUCTION: Treatment with dopamine agonists in patients with prolactin (PRL) adenomas and Parkinson's disease is associated with central side effects. Central side effects may depend on a substance's ability to pass the blood-brain barrier, which can be actively controlled by transporter molecules such as the P glycoprotein (P-gp) encoded by the ABCB1 gene. MATERIALS AND METHODS: We aimed to determine whether cabergoline is transported by the P-gp and whether polymorphisms of its encoding ABCB1 gene predict central side effects of cabergoline therapy in patients with PRL adenomas. i) In an experimental mouse model lacking the homologues of the human ABCB1 gene (Abcb1ab double knockout mouse model), we examined whether cabergoline is a substrate of the P-gp using eight mutant and eight wild-type mice. ii) In a human case-control study including 79 patients with PRL adenomas treated with cabergoline at the Max Planck Institute of Psychiatry in Munich, we investigated the association of four selected ABCB1 gene single nucleotide polymorphisms (SNPs) (rs1045642, rs2032582, rs2032583 and rs2235015), with the occurrence of central side effects under cabergoline therapy. RESULTS: i) In the experimental mouse model, we observed that brain concentrations of cabergoline were tenfold higher in the mutant mice compared with their wild-type littermates, implying that cabergoline is indeed a substrate of the transporter P-gp at the blood-brain barrier level. ii) In the human study, we observed significant negative associations under cabergoline for the C-carriers and heterozygous CT individuals of SNP rs1045642 with two central side effects (frequency of fatigue and sleep disorders) and for the G-carriers of SNP rs2032582 with the enhancement of dizziness. For the SNPs rs2235015 and rs2032583, no associations with central side effects under cabergoline were found. DISCUSSION: This is the first study demonstrating that individual ABCB1 gene polymorphisms, reflecting a different expression and function of the P-gp, could predict the occurrence of central side effects under cabergoline. Our findings can be viewed as a step into personalised therapy in PRL adenoma patients. PMID- 22672925 TI - The study of bone demineralization and its risk factors in an Afro-Caribbean subset of patients with inflammatory bowel disease. AB - INTRODUCTION: Bone demineralization has been increasingly recognized as a disease process concurrent with inflammatory bowel disease (IBD). Racial variation in osteoporosis in IBD patients has been poorly described. We sought to identify the risk factors for demineralization in Afro-Caribbeans (AC) with IBD. METHODS: A retrospective chart review was performed from a 10-year prospectively collected database of IBD patients seen at an urban medical center. Data on dual-energy X ray absorptiometry (DXA) scanning, use of steroids, bisphosphonates, calcium, and vitamin D, as well as blood chemistries were collected. RESULTS: One hundred and fifteen charts of AC IBD patients were reviewed, of which 24 patients had undergone DXA scanning. Fourteen patients with a T-score of less than -1 were compared with 10 patients with DXA scores of more than -1. Two patients with T scores of less than -1 had fractures, whereas none were observed in the comparison group (P=0.5). The mean BMI for those with T-scores of less than -1 was 23.9 kg/m compared with 31.5 kg/m in those with T-scores of more than -1 (P=0.0034). CONCLUSION: Screening for bone demineralization in ethnic populations with IBD is lacking as only 21% of AC IBD patients seen in our institution had undergone a DXA scan. Of those who were scanned, more than half of the patients had T-scores suggestive of bone demineralization. Although those who were obese did not have demineralization, our sample sizes were small and the results from this study should prompt further investigation to determine the prevalence and significance of bone demineralization in minority populations with IBD. PMID- 22672926 TI - Intraoperative gamma cameras for radioguided surgery: technical characteristics, performance parameters, and clinical applications. AB - Several small gamma cameras (SGCs) intended for surgical use are now in development or currently being marketed. In this review, we discuss the characteristics, performance, and clinical use of SGCs which are hand-held and small enough to be easily managed by surgeons during their procedures. We expect that SGCs have the potential to be used more widely in radioguided surgery. As advancing molecular imaging technologies will broaden clinical indications, SGCs will likely be used and integrated with other imaging modalities into numerous types of radioguided surgery in the near future. PMID- 22672927 TI - The potential role of the striatum in antisocial behavior and psychopathy. AB - In this review, we examine the functions of the striatum and the evidence that this brain region may be compromised in antisocial individuals. The striatum is involved in the processing of reward-related information and is thus important in reward-based learning. We review evidence from a growing number of brain imaging studies that have identified differences in the structure or functioning of the striatum either in antisocial groups or in relation to personality traits that are associated with antisocial behavior such as impulsivity and novelty seeking. Evidence from structural imaging studies suggests that the volume of the striatum is increased in antisocial populations, although evidence of localization to specific subregions is inconsistent. Functional imaging studies, which similarly tend to find increased functioning in the striatum, suggest that the striatum is not necessarily hypersensitive to the receipt of reward in antisocial individuals but instead may not be appropriately processing the absence of a reward, resulting in continuous responding to a stimulus that is no longer rewarding. This may impair the ability of individuals to flexibly respond to the environment, thus contributing to impulsivity and antisocial behavior. We conclude by discussing genetic and environmental factors that may affect the development of the striatum. PMID- 22672929 TI - What's going on during the debriefing of a simulation session? PMID- 22672930 TI - Neurophysiological monitoring in adult and pediatric intensive care. AB - Clinical neurophysiology is both an extension of clinical examination and an integration of neuroimaging. It plays a role in diagnosis, prognosis and monitoring in the Intensive Care Unit (ICU). Electroencephalography (EEG) and somatosensory evoked potentials (SEPs) are the most informative neurophysiological tests. Both have a major prognostic role in the hypoxic ischemic encephalopathy and traumatic brain injury (TBI). In the former the absence of bilateral cortical SEPs has an unfavorable prognostic significance of 100%, whereas bilateral normal SEPs has uncertain prognostic value. In TBI these SEP patterns have high early prognostic value for both bad and good outcome. Continuous EEG monitoring is indicated for diagnosis and treatment of non convulsive seizures and status epilepticus (NCSE), whereas SEPs are more able to indicate the occurrence of neurological deterioration. In our opinion EEG-SEP monitoring is also valuable for interpretation and management of ICP trends, contributing to optimise treatment in a single patient. The EEG seems to have the same prognostic utility in pediatric as in adult ICU. Recent reviews supported the use of SEPs in the integrated process of outcome prediction after acute brain injury in children. However differences in interpretation are needed and the issue is whether it is possible to establish an age limit over which the prediction of SEPs is similar to that in adults. There are only a few studies of seizure prevalence in pediatric ICU. The variability of frequency of NCSE in comatose children is high as in adults and, similar to the adult, remains unclear the impact on outcome. PMID- 22672928 TI - Effects of chronic cocaine self-administration on cognition and cerebral glucose utilization in Rhesus monkeys. AB - BACKGROUND: Chronic cocaine use is associated with neurobiological and cognitive deficits that persist into abstinence, hindering success of behavioral treatment strategies and perhaps increasing likelihood of relapse. The effects of current cocaine use and abstinence on neurobiology and cognition are not well characterized. METHODS: Adult male rhesus monkeys with an extensive cocaine self administration history (~ 5 years) and age-matched control animals (n = 4/group) performed cognitive tasks in morning sessions and self-administered cocaine or food in afternoon sessions. Positron emission tomography and [(18)F] fluorodeoxyglucose were employed to assess cerebral metabolic rates of glucose utilization during cognitive testing. RESULTS: Cocaine-experienced monkeys required significantly more trials and committed more errors on reversal learning and multidimensional discriminations, compared with control animals. Cocaine naive, but not cocaine-experienced, monkeys showed greater metabolic rates of glucose utilization during a multidimensional discrimination task in the caudate nucleus, hippocampus, anterior and posterior cingulate, and regions associated with attention, error detection, memory, and reward. Using a delayed match-to sample task, there were no differences in baseline working memory performance between groups. High-dose cocaine self-administration disrupted delayed match-to sample performance but tolerance developed. Acute abstinence from cocaine did not affect performance, but by day 30 of abstinence, accuracy increased significantly, while performance of cocaine-naive monkeys was unchanged. CONCLUSIONS: These data document direct effects of cocaine self-administration on cognition and neurobiological sequelae underlying cognitive deficits. Improvements in working memory can occur in abstinence, albeit across an extended period critical for treatment seekers, suggesting pharmacotherapies designed to enhance cognition may improve success of current behavioral modification strategies. PMID- 22672931 TI - Why are we still mesmerized by the old fashioned Medicine Man? PMID- 22672932 TI - Right ventricular failure in acute lung injury and acute respiratory distress syndrome. AB - Acute respiratory distress syndrome (ARDS) is a clinical entity involving not only alveolar lesions but also capillary lesions, both of which have deleterious effects on the pulmonary circulation, leading to constant pulmonary hypertension and to acute cor pulmonale (ACP) in 20-25% of patients ventilated with a limited plateau pressure (Pplat). Considering the poor prognosis of patients suffering from such acute right ventricular (RV) dysfunction, RV protection by appropriate ventilatory settings has become a crucial issue in ARDS management. The goal of this review is to emphasize the importance of analyzing RV function in ARDS, using echocardiography, in order to limit RV afterload. Any observed acute RV dysfunction should lead physicians to consider a strategy for RV protection, including strict limitation of Pplat, diminution of positive end-expiratory pressure (PEEP) and control of hypercapnia, all goals achieved by prone positioning. PMID- 22672933 TI - Unsupervised feature relevance analysis applied to improve ECG heartbeat clustering. AB - The computer-assisted analysis of biomedical records has become an essential tool in clinical settings. However, current devices provide a growing amount of data that often exceeds the processing capacity of normal computers. As this amount of information rises, new demands for more efficient data extracting methods appear. This paper addresses the task of data mining in physiological records using a feature selection scheme. An unsupervised method based on relevance analysis is described. This scheme uses a least-squares optimization of the input feature matrix in a single iteration. The output of the algorithm is a feature weighting vector. The performance of the method was assessed using a heartbeat clustering test on real ECG records. The quantitative cluster validity measures yielded a correctly classified heartbeat rate of 98.69% (specificity), 85.88% (sensitivity) and 95.04% (general clustering performance), which is even higher than the performance achieved by other similar ECG clustering studies. The number of features was reduced on average from 100 to 18, and the temporal cost was a 43% lower than in previous ECG clustering schemes. PMID- 22672934 TI - 3D hybrid wound devices for spatiotemporally controlled release kinetics. AB - This paper presents localized and temporal control of release kinetics over 3 dimensional (3D) hybrid wound devices to improve wound-healing process. Imaging study is performed to extract wound bed geometry in 3D. Non-Uniform Rational B Splines (NURBS) based surface lofting is applied to generate functionally graded regions. Diffusion-based release kinetics model is developed to predict time based release of loaded modifiers for functionally graded regions. Multi-chamber single nozzle solid freeform dispensing system is used to fabricate wound devices with controlled dispensing concentration. Spatiotemporal control of biological modifiers thus enables a way to achieve target delivery to improve wound healing. PMID- 22672935 TI - Regulation of USP7/HAUSP in response to DNA damage: yet another role for ATM. PMID- 22672936 TI - Polo-like kinase 1 directs the AMPK-mediated activation of myosin regulatory light chain at the cytokinetic cleavage furrow independently of energy balance. AB - It has been recently proposed that AMP-activated protein kinase (AMPK) might indirectly promote the phosphorylation of MRLC (myosin II regulatory light chain) at Ser19 to regulate the transition from metaphase to anaphase and the completion of cytokinesis. Although these findings provide biochemical support for our earlier observations showing that the active form of the alpha catalytic AMPK subunit associates dynamically with essential mitotic regulators, several important issues remained unexplored. Does glucose starvation alter the ability of AMPK to bind to the mitotic apparatus and travel from centrosomes to the spindle midzone during mitosis and cytokinesis? Does AMPK activate MRLC exclusively at the cleavage furrow during cytokinesis? What is the mitosis specific stimulus that activates the mito-cytokinetic AMPK/MRLC axis regardless of energy deprivation? First, we confirm that exogenous glucose deprivation fails to alter the previously described distribution of phospho-AMPKalpha(Thr172) in all of the mitotic phases and does not disrupt its apparent association with the mitotic spindle and other structures involved in cell division. Second, we establish for the first time that phospho-AMPKalpha(Thr172) colocalizes exclusively with Ser19-phosphorylated MRLC at the cleavage furrow of dividing cells, a previously unvisualized interaction between phospho-AMPKalpha(Thr172) and phospho-MRLC(Ser19) that occurs in cleavage furrows, intercellular bridges and the midbody during cell division that appears to occur irrespective of glucose availability. Third, we reveal for the first time that the inhibition of AMPK mitotic activity in response to PLK1 inhibition completely prevents the co localization of phospho-AMPKalpha(Thr172) and phospho-MRLC(Ser19) during the final stages of cytokinesis and midbody ring formation. Because PLK1 inhibition efficiently suppresses the AMPK-mediated activation of MRLC at the cytokinetic cleavage furrow, we propose a previously unrecognized role for AMPK in ensuring that cytokinesis occurs at the proper place and time by establishing a molecular dialog between PLK1 and MRLC in an energy-independent manner. PMID- 22672938 TI - Limb apraxia in a patient with cerebral infarct: diffusion tensor tractography study. AB - We report on a patient with ideomotor apraxia (IMA) and limb-kinetic apraxia (LKA) following cerebral infarct, which demonstrated neural tract injuries by diffusion tensor tractography (DTT). A 67-year-old male was diagnosed as cerebral infarct in the left frontal cortex (anterior portion of the precentral gyrus and prefrontal cortex) and centrum semiovale. The patient presented with severe paralysis of the right upper extremity and mild weakness of the right lower extremity at onset. At the time of DTT scanning (5 months after onset), the patient was able to move all joint muscles of the right upper extremity against gravity, except for the finger extensors, which he could extend partially against gravity. The patient showed intact ideational plan for motor performance; however, his movements were slow, clumsy, and mutilated when executing grasp release movements of his affected hand. The patient's score on the ideomotor apraxia test was 20 (cut-off score < 32). DTTs for premotor cortex fibers, supplementary motor area fibers, and superior longitudinal fasciculus of the left hemisphere showed partial injuries, compared with those of the right side, and these injuries appeared to be responsible for IMA and LKA in this patient. PMID- 22672937 TI - Decreased efficiency of MSH6 mRNA polyadenylation linked to a 20-base-pair duplication in Lynch syndrome families. PMID- 22672939 TI - A corrected version of the Timed-25 Foot Walk Test with a dynamic start to capture the maximum ambulation speed in multiple sclerosis patients. AB - BACKGROUND: No clinical test is currently available and validated to measure the maximum walking speed (WS) of multiple sclerosis (MS) patients. Since the Timed 25-Foot Walk Test (T25FW) is performed with a static start, it takes a significant proportion of the distance for MS patients to reach their maximum pace. OBJECTIVES: In order to capture the maximum WS and to quantify the relative impact of the accelerating phase during the first meters, we compared the classical T25FW with a modified version (T25FW(+)allowing a dynamic start after a 3 meters run-up. METHODS: Sixty-four MS patients and 30 healthy subjects performed successively the T25FW and the T25FW(+). RESULTS: The T25FW(+)was performed faster than the T25FW for the vast majority of MS and healthy subjects. In the MS population, the mean relative gain of speed due to the dynamic start on T25FW(+) was independent from the EDSS and from the level of ambulation impairment. Compared to healthy subjects, the relative difference between dynamic versus static start was more important in the MS population even in patients devoid of apparent gait impairment according to the T25FW. CONCLUSION: The T25FW(+)allows a more accurate measurement of the maximum WS of MS patients, which is a prerequisite to reliably evaluate deceleration over longer distance tests. Indirect arguments suggest that the time to reach the maximum WS may be partially influenced by the cognitive impairment status. The maximum WS and the capacity of MS patients to accelerate on a specific distance may be independently regulated and assessed separately in clinical trials and rehabilitation programs. PMID- 22672940 TI - Ability of three motor measures to predict functional outcomes reported by stroke patients after rehabilitation. AB - OBJECTIVE: This investigation examined the demographic characteristics along with 3 measures of motor function in determining outcomes in activities of daily living (ADL) after distributed constraint-induced therapy (dCIT). METHODS: The study recruited 69 stroke patients who received 3 weeks of dCIT for 2 hours daily, 5 days a week. The self-reported outcome measures for daily function were the Motor Activity Log (MAL) including the amount of use (AOU) and quality of movement (QOM), Nottingham Extended Activities of Daily Living Questionnaire (NEADL), and the Stroke Impact Scale (SIS). Age, sex, onset, side of stroke, Fugl Meyer assessment (FMA), Wolf Motor Function Test (WMFT), and Action Research Arm Test (ARAT) were the potential predictors. RESULTS: The ARAT grasp-grip-pinch score was the most dominant predictor for MAL-AOU and NEADL (P< 0.05), and the ARAT total score for the subscore of the ADL/instrumental ADL section of the SIS (P< 0.05). The FMA wrist-hand score was a significant predictor for MAL-QOM (P< 0.05). Age was the only demographic factor that significantly predicted NEADL performance (P< 0.05). CONCLUSION: Among the 3 commonly used measures of motor function after stroke, ARAT was the strongest determinant in predicting MAL-AOU, MAL-QOM, and SIS-ADL/instrumental ADL after dCIT. PMID- 22672941 TI - Neurorehabilitation with versus without resistance training after botulinum toxin treatment in children with cerebral palsy: a randomized pilot study. AB - OBJECTIVE: To compare the effects of physical rehabilitation with (PRT) and without (CON) progressive resistance training following treatment of spastic plantarflexors with botulinum toxin type A (BoNT) in children with cerebral palsy (CP). METHODS: Fourteen children with CP performed supervised PRT (n=7) or CON (n=7) two times per week for 12 weeks, following the BoNT-treatment. Outcome measurements were performed at baseline (pre BoNT), and 4 and 12 weeks post BoNT. They consisted of: ankle muscle function (maximal torque and submaximal torque steadiness of isometric ankle dorsi- and plantarflexion and associated ankle muscle [EMG] activity), gait function (3-dimensional gait analysis), balance function (sway analysis), gross motor function (GMFM-66), and spasticity (modified Ashworth). RESULTS: Submaximal torque control (torque steadiness) of isometric dorsiflexion improved similarly in the two groups, and the improvement was related to the reduction in antagonist (soleus) co-activity (P< 0.05). Maximal plantarflexion torque increased after PRT, whereas a reduction was seen after CON (P< 0.05). No changes in function were observed. CONCLUSIONS: Both types of physical rehabilitation in combination with BoNT-treatment improved antagonist (ankle dorsiflexion) torque-control to the same extent - which was related to the reduction in antagonist co-activity - but only rehabilitation with PRT increased maximal plantarflexion torque. PMID- 22672942 TI - The vibratory stimulus as a neurorehabilitation tool for stroke patients: proof of concept and tolerability test. AB - INTRODUCTION: Current scientific knowledge reinforces that successful reorganization of surviving nervous tissue supports cognitive and motor recovery after stroke. The development of new neurorehabilitation tools to modulate this physiologic process is needed. In this context, vibratory stimuli are a noninvasive form of proprioceptive stimulation of the nervous system and are freely available and easy to use at a low cost. OBJECTIVES: To access the feasibility and tolerability of targeted vibratory stimuli delivered through a wearable device in an early post-stroke setting. PATIENTS AND METHODS: Five stroke patients were recruited from a stroke unit setting having a first ever medial cerebral artery ischemic stroke with motor deficit. The stimulation device developed delivered external vibratory stimuli to major joints at preprogrammed arrays of intensity, duration and interval of actuation. The tolerability test was set for five-hour duration and during that period data on vital parameters, cognitive, motor and sensitive performance as well as anxiety scores were recorded. RESULTS: The device remained in place throughout and none of the patients or relatives asked to interrupt the tolerability test. There were no major complications during the trial or the ensuing days. Attention to the affected side during stimulation was increased in four patients, and two were reported as clearly more awake during the test. DISCUSSION: This is the first tolerability test focused on the use of targeted vibratory stimulus as a neurorehabilitation tool in stroke patients. There were no hazards to report and most interestingly the majority of patients showed increased awareness to the affected side of the body. These findings will be further analyzed under functional MRI control and on long-term ambulatory use trials. PMID- 22672943 TI - Rehabilitation improves dyskinesias in Parkinsonian patients: a pilot study comparing two different rehabilitative treatments. AB - GOAL AND OBJECTIVES: The present study was devised: (a) to test whether an intensive (60 hours in 4 weeks) multidisciplinary rehabilitation treatment (involving physiotherapy, exercises to improve gait and balance using treadmill and stabilometric platform, occupational therapy) for Parkinsonian patients is effective in improving dyskinesia and motor performance compared to a control group undergoing a non-intensive non multidisciplinary rehabilitation treatment (30 hours in 4 weeks involving physiotherapy only); and (b) to verify whether rehabilitation may lead to a reduction in levodopa dosage. MATERIAL AND METHODS: Forty Parkinsonian patients suffering from dyskinesias were admitted to study: 20 for an intensive multidisciplinary (Group1) and 20 for a non-intensive non multidisciplinary rehabilitation treatment (Group2). The rating scales used for the clinical evaluation were: Unified Parkinson's Disease Rating Scales (UPDRS) II, III, IV, Parkinson's disease disability scale (PDDS), Abnormal Involuntary Movement Scale (AIMS). RESULTS: All outcome measurements improved in both groups of patients, but patients Group1 presented better results: UPDRS II was reduced by 33% in Group1 and by 22% in Group2, UPDRS III 29% vs. 22%, UPDRS IV 74% vs. 10%, PDDS 18% vs. 12%, and AIMS 71% vs. 8%. A different behaviour was observed for levodopa dosage at baseline and after treatment: dosage decreased by an average value of 210 mg (p< 0.0001) in Group1 and was virtually unchanged (30 mg reduction, p=0.08) in Group2. CONCLUSION: Our findings suggest that a rehabilitation protocol should be considered as a valid non-invasive therapeutic support for patients who show dyskinesias and that there are better results when the treatment is intensive. PMID- 22672944 TI - Ipsilateral motor pathway without contralateral motor pathway in a stroke patient. AB - The ipsilateral motor pathway from the unaffected motor cortex to the affected extremity is one of the mechanisms of motor recovery following stroke. We report on a stroke patient who showed the ipsilateral motor pathway without the contralateral motor pathway on functional MRI and diffusion tensor tractography. A 53-year-old left hemiparetic patient with an infarct in the right middle cerebral artery territory was evaluated. During a period of three months after onset, motor function of the affected (left) hand had recovered slowly, to the extent that the patient was able to overcome gravity. FMRI showed that only the unaffected (left) primary sensorimotor cortex was activated by movements of the unaffected (right) hand or of the affected (left) hand. On diffusion tensor tractography, the corticospinal tract of the left hemisphere originated from the primary sensori-motor cortex and descended through the known corticospinal tract pathway. By contrast, the right corticospinal tract showed a disruption with Wallerian degeneration to the upper medulla. We conclude that the motor function of the affected (left) hand appeared to be controlled only by the ipsilateral motor pathway from the left motor cortex to the left hand. Motor function of the affected hand appeared to have been reorganized to the ipsilateral motor pathway from the unaffected motor cortex to the affected hand. PMID- 22672945 TI - Motor point location index using regression equations for the tibialis anterior muscle. AB - PURPOSE: The present study highlighted a novel motor point location index (MPLI) for the precise localization of the motor point (MP) of the tibialis anterior (TA) using a regression equation. METHODS: Twenty healthy young adults (female=8; mean age +/- SD=18.50 +/- 0.32) were volunteered for this study. The regression analysis was performed by correlating the MP locations with anatomical landmarks. The TA muscle's MP location was bilaterally determined by needle electromyography (EMG) measurement. The anatomical landmarks included lower leg length (LLL), tibial tuberosity-intermalleolar line length (TT-ILL), the knee width (KW) and the leg width (LW). RESULTS: The excellent correlation between the TT-ILL and the vertical MP location was obtained, R(2) 0.815. Approximately 82% of the variance of the vertical MP location was accounted for by its linear relationship with the TT-ILL. The high correlation between the LW and the horizontal MP location was observed, R(2)=0.764. Approximately 77% of the variance of the horizontal MP location index was accounted for by its linear relationship with the LW. CONCLUSIONS: These findings indicate that the anatomical landmarks were useful to accurately predict MP locations for the TA muscle. Clinically, this MP location index using regression equations may be alternative for the current method that was not previously affordable. PMID- 22672946 TI - Relationship between the modified Rankin Scale and the Barthel Index in the process of functional recovery after stroke. AB - OBJECTIVE: The modified Rankin Scale (mRS) and the Barthel Index (BI) are the most common clinimetrical instruments for measuring disability after stroke. This study investigated the relationship between the BI and the mRS at multiple time points after stroke. The BI, which is a widely used instrument for longitudinal follow-up post-stroke, was used as reference to determine the effect of time on the sensitivity of the mRS in differentiating functional recovery. METHODS: Ninety-two patients with first stroke and hemispheric brain lesion were evaluated using the BI and mRS at 10 days, 3 and 6 months. The Kruskal-Wallis test was applied to examine median differences in BI among the mRS levels at 10 days, 3 and 6 months with Dunn's correction for multigroup comparison. The Mann and Whitney test was used to compare median differences in BI scores between two aggregations of mRS grades (mRS=0-2, mRS=3-5) at the same time periods after stroke. RESULTS: BI score distribution amongst mRS grades overlapped at 10 days, differentiating only between extreme grades (no disability vs severe disability). At 3 months, independent patients with slight disability could be distinguished from dependent patients with marked disability. At 6 months, grade 2 and 3 overlapped no more, differentiating independence (class 0-2) from dependence (class 3-5). The largest transition to an independent functional status occurred from grade 4, at 3 months. CONCLUSION: Maximum sensitivity of mRS in differentiating functional recovery is reached at six months post-stroke. PMID- 22672947 TI - Neural injury of uncinate fasciculus in patients with diffuse axonal injury. AB - The recent development of diffusion tensor imaging (DTI) allows visualization and estimation of the uncinate fasciculus (UF). We investigated injuries of the UF in patients with diffuse axonal injury (DAI) who showed no specific lesions except for DAI lesions on conventional brain MRI. Twenty-one chronic patients with DAI, and 21 age- and sex-matched normal control subjects were recruited for this study. Diffusion tensor images were acquired using a sensitivity-encoding head coil at 1.5 T and the UF was reconstructed using DTI-Studio software. Fractional anisotropy (FA), apparent diffusion coefficient (ADC) value, and fiber number of the UF were measured. In the DAI group, the FA values and fiber numbers were significantly decreased compared to those of the control group (P< 0.05). The FA value and fiber number decreased 8.4% and 26.5% in the DAI group compared to those of the control group. By contrast, the ADC value did not show any difference between the DAI and control groups (P> 0.05). Changes in the DTI parameters of the DAI group appeared to indicate neural injury of the UF. We believe that DTI can be a useful evaluation tool for detecting hidden neural injuries of UF in patients with DAI. PMID- 22672948 TI - Rapid resolution of akinetic mutism in delayed post-hypoxic leukoencephalopathy with intravenous magnesium sulfate. AB - OBJECTIVE/BACKGROUND: Delayed post-hypoxic leukoencephalopathy is a rare condition marked by the development of neuropsychiatric symptoms, parkinsonism and akinetic mutism days to weeks after an individual has recovered from a prolonged cerebral hypoxic event. This syndrome can cause significant long-term neurologic dysfunction. At present there are no acute treatment strategies that have been identified that have been shown to alter the natural course of this disorder. In most instances all that can be offered to patients is early supportive care and then subsequent rehabilitation services. METHODS: Case Report. RESULTS: A patient is presented who developed new onset encephalopathy, extrapyramidal symptoms and akinetic mutism three weeks after being discharged for a respiratory arrest from a drug overdose. MRI showed the development of extensive white matter and bilateral globus pallidus lesions. She had rapid resolution of akinetic mutism with intravenous magnesium sulfate as well as improvement in her other associated neurologic symptoms. CONCLUSION: The case report suggests the use of intravenous magnesium sulfate as an acute treatment for the akinetic mutism associated with delayed post-hypoxic leukoencephalopathy. In addition it also may improve the extrapyramidal and neuropsychiatric symptoms associated with this syndrome. This may be the first potential acute treatment for this rare neurologic condition. PMID- 22672949 TI - The effect of trigger point management by positional release therapy on tension type headache. AB - OBJECTIVE: The aim of this study was to compare the effectiveness of trigger points' management by Positional Release Therapy (PRT) and routine medical therapy in treatment of Tension Type Headache. BACKGROUND: Tension Type Headache is the most frequent headache with the basis of myofascial and trigger point disorders. PRT is an indirect technique that treats trigger points. METHOD: 30 Patients with active trigger points in cervical muscles entered to the study. They were randomly assigned to PRT or medical therapy group. Headache frequency, intensity and duration and tablet count were recorded by use of a daily headache diary. Sensitivity of trigger points was assessed by numeric pain intensity and by use of a digital force gauge (FG 5020). RESULTS: Both groups showed significant reduction in headache frequency and duration and tablet count after treatment phase. However, the reduction of study variables was persisted only in PRT group after follow up phase. There was no significant reduction in headache intensity, neither in PRT and nor in medication group. Sensitivity of trigger points was significantly reduced. In comparison of the two study groups, there was no significant difference in headache frequency, intensity, duration and tablet count (p> 0.05). CONCLUSION: Both procedures were equally effective according to the study. Thus, PRT can be a treatment choice for patients with T.T.H. PMID- 22672950 TI - Instructions emphasizing speed improves hemiparetic arm kinematics during reaching in stroke. AB - BACKGROUND: Stroke severely compromises the capacity for skilled motor control including the ability to reach with the stroke-affected upper-extremity. Research incorporating intensive motor therapies has broadly demonstrated the ability to improve hemiparetic reaching post-stroke, yet the role of specific task parameters has received less attention. These task parameters, such as speed-of performance, may be important to the structure and delivery of motor rehabilitation. The objective of the study was to determine the influence of task pacing demands on hemiparetic reaching strategies in survivors of stroke. METHODS: Kinematic motion analysis was used to examine upper-extremity reaching patterns in 11 survivors of stroke. Participants were instructed to reach between two targets at a self-selected pace and as fast as possible. Outcome measures included maximal movement speed, accuracy, movement smoothness, and reaching strategies (anterior trunk flexion, elbow extension, and shoulder flexion). RESULTS: Participants reached significantly faster and smoother during the task that emphasized speed while maintaining target accuracy. Participants used significantly less anterior trunk displacement during the fast condition, yet no change in shoulder flexion. CONCLUSION: Task parameters that emphasize speed positively influence reaching strategies with the more-affected upper-extremity. Survivors of stroke were able to respond to changes in pacing demands while significantly reducing reliance on compensatory trunk movement. This outcome highlights the need to further understand the impact of task parameters during intensive motor therapies. PMID- 22672951 TI - The effect of supervised exercises on static and dynamic balance in Parkinson's disease patients. AB - BACKGROUND/AIM: The aim of the this study was to examine the effects of supervised exercises on measures of static and dynamic balance Parkinson's disease (PD) patients. MATERIAL AND METHODS: The study used a before-after study design. Seventeen PD patients with mild and moderate levels of disability were enrolled in the study. Patients followed an exercise program under a physiotherapist's supervision one day a week for 12 weeks. The standard Balance Master protocol was used before and after exercise to assess static and dynamic balance. RESULTS: A statistically significant difference was observed in the unilateral balance test, one of the static balance assessments performed while standing on the left or right leg with eyes closed (p < 0.05). With respect to dynamic balance, a statistically significant difference in the maximum excursion of limits of stability (LOS), one of the balance tests used in the supervised exercise programs for patient with Parkinson's disease, between measurements taken before and after exercises was also detected (p < 0.05). CONCLUSIONS: The change of LOS revealed that dynamic balance improved due to the exercises. Thus, our supervised exercise program provided improvement in dynamic balance of PD patients. PMID- 22672952 TI - The prediction of gross motor outcome using cerebrovascular reserve measured by acetazolamide-challenged SPECT. AB - The purpose of this study was to evaluate the relationship between the recovery of gross motor function and cerebrovascular reserve (CVR) capacity measured by brain perfusion single-photon emission computed tomography (SPECT) in patients with first-ever supratentorial infarction. Gross motor function was assessed according to the locomotor and mobility subset of the functional independence measure. The CVR was measured as the difference in the regional cerebral blood flow (rCBF) after acetazolamide (ACZ)-challenged(99m)Tc-ECD perfusion SPECT from baseline rCBF. All 22 hemiplegic patients (mean age, 60.97 years) enrolled were admitted at a mean of 20.86 days from onset and received rehabilitation care for an average of 38.82 days. The recovery of gross motor function was significantly correlated with baseline rCBF and CVR of ACZ-SPECT in the areas of affected supratentorial hemisphere (r=0.447 and r=0.444, respectively, p < 0.05). Analysis of the linear regression model, adjusted for time to SPECT testing, revealed that the CVR in the affected supratentorial hemisphere was a significant predictor of the gross motor outcome (p< 0.05). In conclusion, the CVR of the affected supratentorial hemisphere may be employed along with other parameters to predict the gross motor recovery of patients with subacute infarction. PMID- 22672953 TI - Upper extremity function and its relation with hand sensation and upper extremity strength in patients with multiple sclerosis. AB - The purpose of this study was to investigate the relationships between the upper extremity functions, upper extremity strength and hand sensation in patients with Multiple Sclerosis (MS). Twenty-two patients with MS (mean age: 38.5 +/- 8.31 years, median Expanded Disability Status Scale (EDSS): 2) and 10 healthy subjects were included. Upper extremity function was measured with the Nine-hole peg test, upper extremity strength (shoulder flexion-abduction, elbow flexion, pinch and grip) with hand-held dynamometer, hand grip dynamometer and manual pinch meter, threshold of light touch-pressure with Semmes-Weinstein monofilament, duration of vibration with 128-Hz frequency tuning fork, and distance of two-point discrimination with an aesthesiometer. Strength and functional level of the upper extremity, light touch-pressure, two-point discrimination, vibration sensations of the hand were lower in patients with MS compared with healthy controls (p < 0.05). Light touch-pressure sensation of thumb and index fingers, two-point discrimination of index finger and elbow flexion strength were found to be related with upper extremity function in patients with MS (p< 0.05). These results indicate that the hand sensation, upper extremity strength and function were affected in MS patients. Additionally upper extremity functions seem to be related with light touch-pressure and two-point discrimination sensations of the hand and elbow flexion strength. Upper extremity strengthening and sensorial training of the hand may contribute to the upper extremity function in patients with MS. PMID- 22672956 TI - Case study on combined CO2 sequestration and low-salinity water production potential in a shallow saline aquifer in Qatar. AB - CO2 is one of the byproducts of natural gas production in Qatar. The high rate of natural gas production from Qatar's North Field (world's largest non-associated gas field) has led to the production of significant amounts of CO2. The release of CO2 into the atmosphere may be harmful from the perspective of global warming. In this work, we study the CO2 sequestration potential in Qatar's Aruma aquifer. The Aruma aquifer is a saline aquifer in the southwest of Qatar. It occupies an area of approximately 1985 km2 on land (16% of Qatar's total area). We have developed a compositional model for CO2 sequestration in the Aruma aquifer on the basis of available log and flow test data. We suggest water production at some distance from the CO2 injection wells as a possible way to control the pore pressure. This method increases the potential for safe sequestration of CO2 in the aquifer without losing integrity of the caprock and without any CO2 leakage. The water produced from this aquifer is considerably less saline than seawater and could be a good water source for the desalination process, which is currently the main source of water in Qatar. The outcome of the desalination process is water with higher salinity than the seawater that is currently discharged into the sea. This discharge can have negative long-term environmental effects. The water produced from the Aruma aquifer is considerably less saline than seawater and can be a partial solution to this problem. PMID- 22672957 TI - Consumers' knowledge of food label information: an exploratory investigation in Potchefstroom, South Africa. AB - OBJECTIVE: To determine the ability of consumers to: locate and manipulate food label information; assess the accuracy of nutrient content claims and which health/nutrient claims are allowed; and identify symbols on food labels. Associations pertaining to use and knowledge regarding food label information were also determined for consumers from different demographic and related groups. DESIGN: An exploratory descriptive study was undertaken, employing a face-to-face survey focusing on demographic information, shopping behaviour, nutrition is important beliefs, label use, label knowledge and label preference and information sources. SETTING: Selected public locations in Potchefstroom in the North West Province of South Africa. SUBJECTS: Respondents (n 229) complying with set inclusion criteria were recruited through purposive sampling. RESULTS: The results indicated respondents' general health and label awareness, as most of them (>80%) could locate label information and identify symbols and specific nutrient content claims although only 53% were able to calculate the number of servings. Nevertheless, an inability was found to assess the accuracy of some nutrient content claims and permissible health/nutrient claims. More educated, younger, Afrikaans- and English-speaking respondents seemed to be more knowledgeable regarding food label information. CONCLUSIONS: Respondents who were informed about nutrition were also informed about label information, while label reading practices resulted in label-influenced purchasing decisions. Educational programmes on food labels should start with nutritional background that could be implemented by consumers during label reading and purchasing decisions. PMID- 22672958 TI - Serum hepatocyte growth factor and cancer mortality in an apparently healthy Japanese population. AB - BACKGROUND: In patients with cancer, hepatocyte growth factor (HGF) is elevated and is a predictor of prognosis. We investigated whether serum HGF was a predictive marker for cancer death in a population of community-dwelling Japanese. METHODS: We studied 1492 apparently healthy Japanese adults who underwent health examinations in 1999. Those who reported a history of liver disease or malignancy on a baseline questionnaire were excluded, and plasma HGF was measured in the remaining 1470 participants, who were followed periodically for 10 years. Multivariate proportional hazards regression was used to estimate cancer mortality. RESULTS: A total of 169 participants died during follow-up (61 from cancer, 32 from cerebrocardiovascular disease, and 76 from other diseases). Mean HGF at baseline was significantly higher among decedents than among survivors (0.26 +/- 0.11 vs 0.23 +/- 0.09 ng/ml, respectively; P < 0.01). The Cox proportional hazards model showed that age, systolic blood pressure, HGF (hazard ratio, 1.27; 95% CI, 1.06-1.52; P = 0.009), albumin level, smoking status, and creatinine were independent predictors of all-cause death. Age, HGF (hazard ratio, 1.31; 95% CI, 1.04-1.65; P = 0.02), and total cholesterol were independent predictive markers for cancer death. CONCLUSIONS: Serum HGF was a predictor of cancer death in an apparently healthy population of community-dwelling Japanese. PMID- 22672959 TI - Relation of serum alpha- and gamma-tocopherol levels to cardiovascular disease related mortality among Japanese men and women. AB - BACKGROUND: There is limited evidence regarding the relationship between serum tocopherol levels and cardiovascular disease. METHODS: We conducted a nested case control study as part of the Japan Collaborative Cohort Study for evaluation of cancer risk (JACC Study). Baseline serum samples were collected from 39 242 participants (age range, 40-79 years) between 1988 and 1990. During the 13-year follow-up, there were 530 stroke deaths (302 ischemic strokes and 210 hemorrhagic strokes) and 211 deaths from coronary heart disease. Controls were matched for sex, age, and area of residence. RESULTS: Serum alpha-tocopherol level was not associated with any type of cardiovascular death in men; however, in women, it was inversely associated with total stroke mortality and hemorrhagic stroke mortality. The multivariate odds ratio (95% CI) for the highest versus the lowest quintile of serum alpha-tocopherol levels among women was 0.35 (0.16-0.77; P for trend = 0.009) for total stroke and 0.26 (0.07-0.97; P for trend = 0.048) for hemorrhagic stroke. Serum gamma-tocopherol was inversely associated with ischemic stroke mortality in men but positively associated with hemorrhagic stroke mortality in women. The respective multivariate odds ratios (95% CI) for the highest versus the lowest quintile and for a 1-standard deviation increment in gamma-tocopherol level were 0.48 (0.22-1.06; P for trend = 0.07) and 0.77 (0.58 1.02), respectively, for ischemic stroke in men and 3.10 (0.95-10.12; P for trend = 0.052) and 1.49 (1.04-2.13) for hemorrhagic stroke in women. CONCLUSIONS: Among women, hemorrhagic stroke mortality was inversely associated with serum alpha tocopherol and positively associated with serum gamma-tocopherol. These findings are due in part to the antioxidative and antithrombotic activities of these tocopherols. PMID- 22672960 TI - Harnessing the incretin system beyond glucose control: potential cardiovascular benefits of GLP-1 receptor agonists in type 2 diabetes. AB - The management of type 2 diabetes continues to evolve as new data emerge. Although glycaemic control is still important, other risk factors--such as hypertension, dyslipidaemia and obesity--must also be addressed in order to reduce the long-term risks of cardiovascular complications and mortality. In this context, targeting the incretin system, and glucagon-like peptide-1 (GLP-1) in particular, has generated much interest. GLP-1 is released from the gut in response to food ingestion and plays a crucial role in glucose homeostasis. GLP-1 receptors are expressed in the heart and vasculature, prompting evaluation of their physiological role and pharmacological stimulation, both in healthy and disease states. These studies indicate that GLP-1 and GLP-1-based therapies appear to have direct, beneficial effects on the cardiovascular system, in addition to their glucose-lowering properties, such as modulation of blood pressure, endothelial function, and myocardial contractility. Intriguingly, some of these effects appear to be independent of GLP-1 receptor signalling. Data from clinical studies of the GLP-1 receptor agonists, exenatide and liraglutide on cardiovascular risk factors, in patients with type 2 diabetes are also promising and the results from prospective studies to assess cardiovascular outcomes are eagerly awaited. PMID- 22672961 TI - Dynamic foot function changes following total knee replacement surgery. AB - BACKGROUND: Individuals with knee osteoarthritis (OA) have flatter/more pronated feet than those without OA, but it is unclear whether altered foot posture and function are a cause or consequence of knee OA. The purpose of this study was to examine whether changes in foot posture and function occur after realignment of the knee following total knee replacement (TKR). MATERIALS AND METHODS: Nineteen patients with predominantly medial compartment knee OA were tested prior to and 12 months after TKR. The Foot Posture Index (FPI) and Arch Index (AI) were measured as well as motion of the tibia, rearfoot and forefoot using a 3D motion analysis system incorporating a multisegment foot model. RESULTS: There were no significant changes in FPI or AI following TKR, however gait analysis revealed significant increases in tibial external rotation (-18.7 +/- 7.0 degrees vs 22.5 +/- 8.7 degrees , p=0.002), tibial transverse plane range of motion (-9.1 +/ 4.6 degrees vs -11.4 +/- 6.1 degrees , p=0.0028) and rearfoot range of motion in the frontal plane (8.6 +/- 2.6 degrees vs 10.4 +/- 2.7 degrees , p=0.002), and a decrease in rearfoot transverse plane range of motion (8.7 +/- 5.3 degrees vs 5.9 +/- 4.1 degrees , p=0.038) following the procedure. CONCLUSIONS: TKR produces no change in static foot posture, but results in significant changes in rearfoot kinematics during gait. These findings suggest that rearfoot motion compensates for changes in the alignment of the knee, highlighting the ability of the foot to accommodate for proximal skeletal malalignment. PMID- 22672962 TI - [Care of older patients: towards collaboration between internal medicine and geriatrics]. PMID- 22672963 TI - [Renal sympathetic denervation in resistant hypertension]. PMID- 22672964 TI - [Advances on breast cancer: a perspective]. PMID- 22672966 TI - [Key points in healthcare of frail elders in the Emergency Department]. AB - Patients older than 65 years are increasingly attended in the Emergency Department (ED). This means that internists working in ED are responsible for improving their geriatric training. The frail elders are the one who have the higher probability to suffer an adverse event. The detection of this profile is very important for making a decision in ED. A possible geriatric emergency model would be the one that screens frailty among all patients older than 65 years old in ED by nurses, and, in those triaged as of high risk, a geriatric assessment must be done by a geriatric trained doctor or nurse. All this information will be helpful for the final location and discharge follow-up plan. PMID- 22672967 TI - [A 37-years old man with recurrent episodes of fever and abdominal pain]. PMID- 22672968 TI - Expression and characterization of recombinant soluble porcine CD3 ectodomain molecules: mapping the epitope of an anti-porcine CD3 monoclonal antibody 898H2-6 15. AB - The porcine CD3 specific monoclonal antibody 898H2-6-15 has been used in allo- and xeno-transplantation studies as a porcine CD3 marker and as an effective T cell depletion reagent when conjugated to the diphtheria toxin mutant, CRM9. A recombinant anti-porcine CD3 immuntoxin was recently developed using single-chain variable fragments (scFv) derived from 898H2-6-15. In this study, using published sequence data, we have expressed the porcine CD3 ectodomain molecules in E. coli through inclusion body isolation and in vitro refolding approach. The expressed and refolded porcine CD3 ectodomain molecules include CD3epsilon, CD3gamma, CD3delta, CD3epsilongamma heterodimer, CD3epsilondelta heterodimer, CD3epsilongamma single-chain fusion protein and CD3epsilondelta single-chain fusion protein. These refolded porcine CD3 ectodomain molecules were purified with a strong anion exchange resin Poros 50HQ. ELISA analysis demonstrated that only the porcine CD3epsilongamma ectodomain single-chain fusion protein can bind to the porcine CD3 specific monoclonal antibody 898H2-6-15. The availability of this porcine CD3epsilongamma ectodomain single-chain fusion protein will allow screening for affinity matured variants of scFv derived from 898H2-6-15 to improve the recombinant anti-porcine CD3 immunotoxin. Porcine CD3epsilongamma ectodomain single-chain fusion protein will also be a very useful reagent to study the soluble phase interaction between porcine CD3epsilongamma and porcine CD3 antibodies such as 898H2-6-15. PMID- 22672969 TI - Prognostic factors for non-small cell lung cancer with bone metastasis at the time of diagnosis. AB - INTRODUCTION: The skeletal system is one of the most common distant sites of metastatic non-small cell lung cancer (NSCLC) which may lead to skeletal-related event (SRE). The purpose of this study was to assess the frequency of SRE and the prognostic factors of overall survival (OS) in patients presenting bone metastasis in NSCLC. METHODS: Two hundred and twenty NSCLC patients with skeletal metastases at the time of diagnosis between January 2000 and August 2007 were investigated retrospectively. RESULTS: Forty-seven of 110 patients (43%) without a SRE at the time of diagnosis experienced their first SRE during the follow-up. Patients with squamous cell carcinoma had a 1.8-times higher risk of short OS [95% confidence interval (CI) 1.11-2.84, p=0.016], compared with patients with non-squamous cell carcinoma, and patients treated with EGFR TKIs achieved a 50% protective effect in OS compared with patients not treated with them (95% CI 0.32 0.80, p=0.004). Patients with ECOG performance status 0-1 and single bone metastasis had a 1.8-times (95% CI 1.13-2.60, p=0.003) and 2.4-times (95% CI 1.26 4.46, p=0.008) longer OS than patients with performance status>=2 and two or more bone metastases, respectively. CONCLUSION: Our study demonstrated that the frequency of SRE was common and single bone metastasis, good performance status (ECOG 0, 1), EGFR TKI treatment had good prognosis and histology of squamous cell carcinoma had bad prognosis. PMID- 22672970 TI - Radical radiotherapy with or without gemcitabine in patients with early stage medically inoperable non-small cell lung cancer. AB - BACKGROUND: Preclinical and phase I data suggest gemcitabine to be a potent radiosensitiser. This multicentre study addressed whether the addition of low dose gemcitabine to radical radiotherapy improved 2 year event-free survival in patients with medically inoperable stages I-II non-small cell lung cancer. AIM: To determine whether low dose gemcitabine increased event-free survival in patients with T1-2 N0-1 M0 NSCLC deemed unfit for surgery. METHODS: Patients with T1-2 N0-1 M0 NSCLC deemed unfit for surgery were randomised to 3D conformal radiotherapy delivering 55 Gy in 20 fractions over 4 weeks to known sites of cancer with (Arm B) or without (Arm A) 100mg/m(2) weekly gemcitabine. RESULTS: Study entry was terminated early because of slow accrual. 111 patients were randomised between March 2003 and December 2005, of whom 4 withdrew consent and 2 were lost to follow-up. Median age was 75 (range 49-88)years and 67 (63%) were male. 86 (81%) were PS 0-1 and 31 (30%) Charlson index 2 or greater. Event-free survival in arm A and B, respectively, was 42% and 46% at 2 years and 20% and 31% at 5 years (p=0.72), while overall survival was 56% and 52% at 2 years and 20% and 33% at 5 years (p=0.87). Two deaths from accelerated interstitial lung disease were seen in arm B, but toxicity was otherwise mild. CONCLUSION: No evidence of an improvement in event-free survival was seen with the addition of weekly gemcitabine at this dose for patients with early stage NSCLC unfit for surgery, although the power of the study was low. PMID- 22672971 TI - A rose by any other name: medical homes. PMID- 22672972 TI - A rare breast tumor: solid neuroendocrine carcinoma. AB - BACKGROUND: Solid neuroendocrine carcinoma of breast (NECB) is extremely rare. In this paper, we present a case of inflammatory primary solid neuroendocrine carcinoma of breast managed by surgery and chemotherapy and a brief review of the epidemiology, clinical features, diagnosis, pathologic features, treatment, and prognosis of solid NECB. METHODS: A 63-year-old woman was admitted in our institution with inflammatory primary solid neuroendocrine carcinoma of breast. A bulky mass of 6,5 cm tumor was located in the upper-outer and intern quadrant of her right breast. The patient underwent neo-adjuvant chemotherapy, and subsequent radical mastectomy with axillary lymph node dissection. Microscopically, the tumor was classified as solid cohesive, the tumor cells were positive for neuroendocrine markers chromogranin A and synaptophysin. 19 lymph nodes of 27 were metastatic. RESULTS: Local recurrence and metastatic progression was noted only one month after the surgery, the patient was managed by chemotherapy and hormone-therapy. She is still alive, 24 months after diagnosis. CONCLUSIONS: Solid neuroendocrine carcinoma is a subtype of mammary carcinoma with several distinctive features. Because of the rarity of this disease, there is no standard treatment, they are characterized by a higher propensity for local and distant recurrence, This case reinforces the importance to explore the novels therapeutics regimen and one of ways to explore is the use of VP16-cisplatine as treatment as it was partially efficacy for this kind of tumor. PMID- 22672973 TI - Relationship of hobby activities with mortality and frailty among community dwelling elderly adults: results of a follow-up study in Japan. AB - BACKGROUND: The proportion of Japanese adults aged 65 years or older is predicted to increase; thus, it is becoming more important to identify factors that influence health status among elderly adults in Japan. We conducted a follow-up study of community-dwelling elderly adults to assess the relationship of hobby activities with mortality and incident frailty. METHODS: We randomly selected 3583 individuals aged 65 to 84 years from the residential registries of 7 study areas in Hokkaido, Japan in August 2007. Among them, 1955 (54.6%) returned completed questionnaires with written informed consent by mail. The baseline assessment questionnaire comprised questions on current and past involvement in hobby activities, self-perceived health status, smoking and drinking habits, and body height and weight. Questions on hobby activities were from 4 categories: solitary physical, group physical, solitary cultural, and group cultural activities. We later conducted a follow-up survey of the participants to ascertain all-cause mortality and incident frailty. A Cox proportional hazards model was used for analysis of data from September 2007 to May 2010. RESULTS: After adjusting for potential confounders, the risk of incident frailty among respondents participating in solitary physical activities was significantly lower than in those who did not participate in such activities (hazard ratio = 0.57; 95% CI 0.33, 0.99). Furthermore, the risk of incident frailty among respondents taking part in group cultural activities was significantly lower than in those who did not participate in such activities (0.41; 0.19, 0.87). CONCLUSIONS: These findings may be important for programs that seek to promote good health among elderly adults. PMID- 22672974 TI - Venous thromboembolism in adult hospitalizations - United States, 2007-2009. AB - Deep vein thrombosis (DVT) is a blood clot that occurs in a deep vein of the body; pulmonary embolism (PE) occurs when a clot breaks free and enters the arteries of the lungs. DVT and PE comprise venous thromboembolism (VTE), an important and growing public health concern. Hospitalization is a major risk factor for VTE, and many VTE events that occur among hospitalized patients can be prevented. A new program of the U.S. Department of Health and Human Services (Partnership for Patients: Better Care, Lower Costs) aims to reduce the number of preventable VTE cases in hospitals. To estimate the number of hospitalizations with VTE each year in the United States, CDC analyzed 2007-2009 data from the National Hospital Discharge Survey (NHDS). The results of that analysis determined that an estimated average of 547,596 hospitalizations with VTE occurred each year among those aged >=18 years in the United States. DVT was diagnosed in an estimated annual average of 348,558 hospitalizations, and PE was diagnosed in 277,549; both DVT and PE were diagnosed in 78,511 hospitalizations. Estimates of the rates of hospitalizations with VTE were substantially higher among adults aged >=60 years compared with those aged 18-59 years. These findings underscore the need to promote implementation of evidence-based prevention strategies to reduce the number of preventable cases of VTE among hospitalized patients. PMID- 22672975 TI - Neonatal herpes simplex virus infection following Jewish ritual circumcisions that included direct orogenital suction - New York City, 2000-2011. AB - Herpes simplex virus (HSV) infection commonly causes "cold sores" (HSV type 1 [HSV-1]) and genital herpes (HSV-1 or HSV type 2 [HSV-2]); HSV infection in newborns can result in death or permanent disability. During November 2000 December 2011, a total of 11 newborn males had laboratory-confirmed HSV infection in the weeks following out-of-hospital Jewish ritual circumcision, investigators from the New York City Department of Health and Mental Hygiene (DOHMH) learned. Ten of the 11 newborns were hospitalized; two died. In six of the 11 cases, health-care providers confirmed parental reports that the ritual circumcision included an ultra-Orthodox Jewish practice known as metzitzah b'peh, in which the circumciser (mohel, plural: mohelim) places his mouth directly on the newly circumcised penis and sucks blood away from the circumcision wound (direct orogenital suction). In the remaining cases, other evidence suggested that genital infection was introduced by direct orogenital suction (probable direct orogenital suction). Based on cases reported to DOHMH during April 2006-December 2011, the risk for neonatal herpes caused by HSV-1 and untyped HSV following Jewish ritual circumcision with confirmed or probable direct orogenital suction in New York City was estimated at 1 in 4,098 or 3.4 times greater than the risk among male infants considered unlikely to have had direct orogenital suction. Oral contact with a newborn's open wound risks transmission of HSV and other pathogens. Circumcision is a surgical procedure that should be performed under sterile conditions. Health-care professionals advising parents and parents choosing Jewish ritual circumcision should inquire in advance whether direct orogenital suction will be performed, and orogenital suction should be avoided. PMID- 22672976 TI - Methodologic changes in the Behavioral Risk Factor Surveillance System in 2011 and potential effects on prevalence estimates. AB - In the past few years, all large population health surveys that depend on telephone interviews, including the Behavioral Risk Factor Surveillance System (BRFSS), have had to adjust to the rapid rise in the proportion of U.S. households that have a cellular telephone but no landline telephone. To maintain survey coverage and validity, surveys have had to add cellular telephone households to their samples. In addition, telephone surveys have had to make adjustments in weighting to account for declining response rates by adopting new methods of weighting to adjust survey data for differences between the demographic characteristics of respondents and the target population. Since 2004, BRFSS has been planning and testing the addition of cellular telephone households and improvements in its methods of statistical weighting. These new methods were implemented during the fielding of the 2011 BRFSS, which is to be released in 2012. This policy note describes the methodologic changes and their potential effects on BRFSS prevalence estimates. Preliminary assessments indicate that the inclusion of cellular telephone respondents and the move to a new method of weighting might increase prevalence estimates for health risk behaviors and chronic disease in many states. Carefully planned communication to public health officials and nonscientific audiences of the effect of changes in methods on estimates is needed to prevent misinterpretation. PMID- 22672977 TI - Update: influenza activity - United States, 2011-12 season and composition of the 2012-13 influenza vaccine. AB - During the 2011-12 influenza season in the United States, influenza activity* occurred at low levels during October through December and increased in January and February before peaking in mid-March. Influenza A (H3N2) viruses predominated overall, but influenza A (H1N1)pdm09 (pH1N1) and influenza B viruses also circulated widely. This influenza season was mild compared with recent years, with a lower percentage of outpatient visits for influenza-like illness (ILI),? lower rates of hospitalizations, and fewer deaths attributed to pneumonia and influenza. This report summarizes influenza activity in the United States during the 2011-12 influenza season (October 2, 2011-May 19, 2012) and reports the recommendations for the components of the 2012-13 Northern Hemisphere influenza vaccine. PMID- 22672978 TI - Notes from the field: investigation of leptospirosis underreporting - Puerto Rico, 2010. AB - Leptospirosis, a zoonosis transmitted through contact with the urine of infected animals, either directly or through exposure to contaminated water or soil, is a frequent cause of acute febrile illness (AFI) and can be difficult to distinguish from dengue in areas where both are endemic. Approximately 5%-10% of patients with leptospirosis are affected severely; the case-fatality rate in those with severe disease is 5%-15%. Early identification of leptospirosis cases and early administration of penicillin G or doxycycline can reduce the duration and severity of illness. PMID- 22672979 TI - Investigations into ultrasound induced atomization. AB - The present work deals with measurements of the droplet size distribution in an ultrasonic atomizer using photographic analysis with an objective of understanding the effect of different equipment parameters such as the operating frequency, power dissipation and the operating parameters such as the flow rate and liquid properties on the droplet size distribution. Mechanistic details about the atomization phenomena have also been established using photographic analysis based on the capture of the growth of the instability and sudden ejection of droplets with high velocity. Velocity of these droplets has been measured by capturing the motion of droplets as streaks. It has been observed that the droplet size decreases with an increase in the frequency of atomizer. Droplet size distribution was found to change from the narrow to wider range with an increase in the intensity of ultrasound. The drop size was found to decrease with an increase in the fluid viscosity. The current work has clearly highlighted the approach for the selection of operating parameters for achieving a desired droplet size distribution using ultrasonic atomization and has also established the controlling mechanisms for the formation of droplet. An empirical correlation for the prediction of the droplet size has been developed based on the liquid and equipment operating properties. PMID- 22672980 TI - Photodynamic inactivation of Candida albicans using bridged polysilsesquioxane films doped with porphyrin. AB - Novel photoactive bridged polysilsesquioxane films were prepared by doped with a porphyrin derivative. The films were formed by acid-catalyzed polycondensation reaction of a precursor of a bridged silsesquioxane, based on the reaction product of (glycidoxypropyl)trimethoxysilane with n-dodecylamine in the presence of 5-(4-carboxyphenyl)-10,15,20-tris(4-methylphenyl)porphyrin, followed by solvent evaporation. This procedure allowed obtaining flexible thin films. Absorption and fluorescence spectroscopic analysis showed the characteristic bands of the porphyrin in the visible region indicating that the photosensitizer is mainly embedded as monomer in the films. Photodynamic properties of the polymeric films were studied in solution containing photooxidizable substrates. Singlet molecular oxygen, O(2)((1)Delta(g)), production was observed by the reaction with 9,10-dimethylanthracene and 9,10-anthracenediyl bis(methylene)dimalonic acid in different media. Also, these films photosensitized the decomposition of l-tryptophan. In vitro investigations showed that these films produce photodynamic inactivation of Candida albicans cells in aqueous suspensions and on their surfaces. These films exhibit a photosensitizing activity causing a ~2.5 log (99.7%) decrease of cellular survival after 60 min of irradiation with visible light. Also, the photocytotoxicity of the surfaces was tested under condition of microbial growth. Yeast cells exposed to the film and illuminated showed growth delay compared with controls. Studies of photodynamic action mechanism showed that the photoinactivation increased in D(2)O, while cells were protected in the presence of azide ion. In contrast, the addition of mannitol produced a negligible effect on the cellular phototoxicity. These results provide evidence that O(2)((1)Delta(g)) produced by the polymeric film doped with porphyrin can successfully inactivate C. albicans in cell suspensions and deposited on the film surface. PMID- 22672981 TI - The cruciferous phytoalexins rapalexin A, brussalexin A and erucalexin: chemistry and metabolism in Leptosphaeria maculans. AB - The interactions of the cruciferous phytoalexins rapalexin A (1), brussalexin A (2) and erucalexin (3) with the fungal plant pathogen Leptosphaeria maculans were analyzed and their inhibitory activities against this pathogen were determined. The reaction of L. maculans to N-methyl S-(indolyl-3-methyl)carbamodithioate, an analogue of brussalexin A, was also investigated. Rapalexin A was resistant to metabolism and was the most inhibitory of all compounds tested, suggesting that increasing concentrations of rapalexin A in Brassica species would improve their disease resistance to L. maculans. By contrast, erucalexin was quickly detoxified by reduction to yield 3-dihydroerucalexins. The relative configurations of the diastereomeric mixture of dihydroerucalexins were established by 1D (1)H nuclear Overhauser enhancement spectroscopy (NOE). Brussalexin A was chemically unstable decomposing mainly to indolyl-3-methanol, a product with anti-cancer properties. For this reason, brussalexin A might be of interest to use as a prodrug. PMID- 22672982 TI - Effects of chemical modification of sphingomyelin ammonium group on formation of liquid-ordered phase. AB - Sphingomyelin (SM) and cholesterol form microdomains called lipid rafts in cellular membranes. To develop a versatile fluorescent lipid probe, chemical modifications to both the hydrophobic and hydrophilic portions of SM are essential. Few reports describing SM probes with a fluorophore at the polar head group have been published. This study examined the effect of substitution on an ammonium moiety of SM on the membrane properties of SM. Two SM analogs with small propargyl and allyl groups on the quaternary nitrogen atom were synthesized and subjected to analysis using differential scanning calorimetry, fluorescent anisotropy, detergent solubilization, surface pressure, and density measurements. Results demonstrated that the two SM analogs retained the membrane properties of SM, including formation of an ordered phase and the ability to interact with cholesterol. A dansyl-substituted SM was prepared for fluorescent measurements. Dansyl-SM showed less of a propensity to form microdomains. These findings imply the potential application of N-substituted SMs as a raft-specific molecular probe. PMID- 22672983 TI - Synthesis of tocopheryl succinate phospholipid conjugates and monitoring of phospholipase A2 activity. AB - Tocopheryl succinates (TOSs) are, in contrast to tocopherols, highly cytotoxic against many cancer cells. In this study the enzyme activity of secretory phospholipase A(2) towards various succinate-phospholipid conjugates has been investigated. The synthesis of six novel phospholipids is described, including two TOS phospholipids conjugates. The studies revealed that the TOS conjugates are poor substrates for the enzyme whereas the phospholipids with alkyl and phenyl succinate moieties were hydrolyzed by the enzyme to a high extent. PMID- 22672984 TI - Antitumor agents 290. Design, synthesis, and biological evaluation of new LNCaP and PC-3 cytotoxic curcumin analogs conjugated with anti-androgens. AB - In our continuing study of curcumin analogs as potential anti-prostate cancer drug candidates, 15 new curcumin analogs were designed, synthesized and evaluated for cytotoxicity against two human prostate cancer cell lines, androgen-dependent LNCaP and androgen-independent PC-3. Twelve analogs (5-12, 15, 16, 19, and 20) are conjugates of curcumin (1) or methyl curcumin (2) with a flutamide- or bicalutamide-like moiety. Two compounds (22 and 23) are C4-mono- and difluoro substituted analogs of dimethyl curcumin (DMC, 21). Among the newly synthesized conjugates compound 15, a conjugate of 2 with a partial bicalutamide moiety, was more potent than bicalutamide alone and essentially equipotent with 1 and 2 against both prostate tumor cell lines with IC(50) values of 41.8 MUM (for LNCaP) and 39.1 MUM (for PC-3). A cell morphology study revealed that the cytotoxicity of curcumin analogs or curcumin-anti-androgen conjugates detected from both prostate cancer cell lines might be due to the suppression of pseudopodia formation. A molecular intrinsic fluorescence experiment showed that 1 accumulated mainly in the nuclei, while conjugate 6 was distributed in the cytosol. At the tested conditions, anti-androgens suppressed pseudopodia formation in PC-3 cells, but not in LNCaP cells. The evidence suggests that distinguishable target proteins are involved, resulting in the different outcomes toward pseudopodia suppression. PMID- 22672985 TI - Activation of the mitogen-activated protein kinase kinase/extracellular signal regulated kinase pathway overcomes cisplatin resistance in ovarian carcinoma cells. AB - OBJECTIVE: This study was aimed to elucidate the roles of the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3'-kinase (PI3K)/Akt pathways in regulating cytotoxicity induced by cisplatin (CDDP) in ovarian carcinoma cells. METHODS: We treated 7 ovarian cancer cell lines with CDDP alone or with CDDP and either a PI3K inhibitor (LY294002), a MEK inhibitor (PD98059), or a MEK/ERK activator (phorbol 12-myristate 13-acetate [PMA]) and assessed cell viability, expression of MEK/ERK and PI3K/Akt, cell cycle distribution, and apoptosis. We also investigated the effect of combination treatment on survival in a xenograft model. RESULTS: The cell lines showed half-maximal inhibitory concentrations (IC50) of CDDP from 2.4 to 26.9 MUmol/L. KFr, a CDDP-resistant cell line developed from KF cells, showed an IC50 of CDDP of 9.6 MUmol/L. Five of the cell lines with IC50 values of 9.6 MUmol/L or greater were defined as CDDP-resistant. Cisplatin and LY294002 had an additive effect on inhibiting cell growth, and CDDP and PD98059 had and antagonistic effect on cell growth in all cell lines. In CDDP-resistant cells, CDDP and PMA dramatically suppressed the cell growth, up-regulated the expression of phosphorylated ERK and cleaved caspase-9, down-regulated the expression of checkpoint kinases, and increased the proportion of cells in the synthesis-phase fraction and apoptotic cells. The treatment of nude mice with CDDP and PMA prolonged survival in an ovarian cancer xenograft model. CONCLUSIONS: The present study indicates that further study is warranted to determine the effectiveness of combination treatment with CDDP and PMA for platinum-resistant ovarian carcinoma. PMID- 22672986 TI - Prospective assessment of quality of life and psychological distress in patients with gynecologic malignancy: a 1-year prospective study. AB - OBJECTIVE: Our aim was to evaluate the health-related quality of life (HRQoL) and psychological distress in patients treated with radiotherapy (RT) for gynecologic malignancy. METHODS: Fifty-seven women with either cervical or endometrial cancer were prospectively enrolled. We assessed HRQoL at baseline (after surgery before RT), at the end of RT, and during follow-up (every 3 months thereafter) using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30), European Organization for Research and Treatment of Cervical Cancer Quality of Life Questionnaire 24 (EORTC QLQ-CX24), and Hospital Anxiety and Depression Scale. RESULTS: We demonstrated changes in appetite loss (P = 0.03), nausea and vomiting (P = 0.02), and role function score (P = 0.003) domains of EORTC QLQ-C30. Only the mean body image score of EORTC QLQ CX24 was significantly different during follow-up (P = 0.02). Type of surgery, histopathological diagnosis, and the menopausal and marital status of the patients affected baseline body image scores (P = 0.032, 0.004, and 0.019 and 0.005, respectively). Patients who underwent chemotherapy had higher baseline body image scores when compared with patients without any chemotherapy before RT (P = 0.028). All the complaints of patients except body image scores improved during the follow-up period. The baseline and follow-up anxiety and depression scores did not differ significantly. CONCLUSIONS: Although pelvic RT deteriorated HRQoL in gynecologic cancer, patients' improvement in HRQoL during follow-up was observed. Patients receiving RT could be reassured about the improvement of acute adverse effects in the course of treatment. PMID- 22672987 TI - Accuracy of several cervical screening strategies for early detection of cervical cancer: a meta-analysis. AB - OBJECTIVE: The objectives of this study were to assess the accuracy of 6 common cervical screening strategies, including visual inspection with acetic acid, with a magnifying device, or with Lugol iodine (VILI), human papillomavirus testing with Hybrid Capture 2 assay, conventional Papanicolaou smear, and thin liquid based cytology (LBC), and then to compare data obtained by the aforementioned 6 strategies. METHODS: PubMed, EMBASE, and The Cochrane Library were systematically searched for all original relevant studies about early detection of cervical cancer. A meta-analysis was performed to evaluate the accuracy of the 6 screening strategies covering sensitivity, specificity, diagnostic odds ratio, and the area under the receiver operating characteristic curve. RESULTS: Fifteen articles containing 22 cross-sectional studies were finally identified. The combined estimates of sensitivity for visual inspection with acetic acid, magnified visual inspection with acetic acid, VILI, Hybrid Capture 2 assay, conventional Papanicolaou smear, and LBC were 77%, 64%, 91%, 74%, 59%, and 88%, respectively; the combined values of specificity of these screening strategies were 87%, 86%, 85%, 92%, 94%, and 88%, respectively; the diagnostic odds ratio were 22.43, 10.30, 57.44, 33.26, 22.49, and 51.56, respectively; and the area under the receiver operating characteristic curve were 0.8918, 0.7737, 0.9365, 0.9486, 0.9079, and 0.9418, respectively. CONCLUSIONS: This meta-analysis suggests that LBC appeared to be promising in primary cervical cancer screening in resourced regions, and VILI might be a good choice to identify/exclude cervical cancerous and precancerous lesions in resource-constrained regions. PMID- 22672988 TI - Splenectomy as part of primary cytoreductive surgery for advanced ovarian cancer: a retrospective cohort study. AB - BACKGROUND: The aim of surgical approach in advanced ovarian cancer should be the complete removal of all visible disease. Our purpose was to compare perioperative features and postoperative complications, and secondarily oncological outcomes, between patients who underwent splenectomy and those who did not at the time of surgery. MATERIALS AND METHODS: Thirty-three subjects underwent splenectomy, and we selected 99 controls with similar surgical characteristics but who did not undergo splenectomy. Data collected included perioperative details and follow-up data. RESULTS: Longer operating time (33 minutes longer; P = 0.02), larger estimated blood loss (812 mL more; P = 0.03), higher rate of intraoperative blood transfusions (78.8% vs 42.4%; P < 0.01), and intensive care unit stay (1.4 vs 0.5 days; P < 0.01) as well as higher pneumonia rate (2% vs 0%; P = 0.01) were observed in the splenectomy group. Disease-free and overall survival rates were 30.3% and 66.6%, respectively, in the splenectomy group, and 33.3% and 59.6%, respectively, in the control group. CONCLUSIONS: Splenectomy at the time of primary cytoreductive surgery for advanced ovarian cancer may contribute to achieve complete cytoreduction with low perioperative complication rate. This procedure seems to be an acceptable and rational intervention to increase the survival rates of those patients. PMID- 22672989 TI - Underexpression of 4 placenta-associated microRNAs in complete hydatidiform moles. AB - OBJECTIVE: Several placental microRNAs (miRNAs) have been identified as placenta associated miRNAs with the potential of estimating the condition of the placenta. However, our understanding of these miRNAs is limited. The aim of this study was to determine the expression of 8 placenta-associated miRNAs (miR-512-3p, miR 517a, miR-517b, miR-518b, miR-519a, miR-1185, miR-1283, and miR-1323) in complete hydatidiform mole (CHM). METHODS: Samples were obtained from patients with CHM (CHM group, n = 12) and elective terminations of normal pregnancy (control group, n = 20). We detected differentially expressed placenta-associated miRNAs in placenta by quantitative real-time reverse transcriptase-polymerase chain reaction analysis. Subsequently, we assessed the expression location of differentially expressed miRNAs by in situ hybridization analysis. RESULTS: Four placenta-associated miRNAs (miR-517a, miR-517b, miR-518b, and miR-519a) were underexpressed in the CHM group, compared with the control group (P < 0.01). When further investigating these 4 miRNAs with regard to in vivo localization by in situ hybridization, we found that 2 miRNAs (miR-517b and miR-518b) were detected exclusively in the trophoblast layer, with little signal (if any) observed in villous stroma cells. CONCLUSIONS: The results show that 4 miRNAs (miR-517a, miR 517b, miR-518b, and miR-519a) are deregulated in CHM, which suggests the involvement of these miRNAs in the functions of CHM placenta. PMID- 22672990 TI - Up regulation of nitric oxide synthase-nitric oxide system in the testis of rats undergoing autoimmune orchitis. AB - BACKGROUND: Male reproductive tract infection and inflammation are important aetiological factors of infertility. Experimental Autoimmune Orchitis (EAO) is a model of chronic inflammation useful to study mechanisms of inflammatory reactions leading to testicular impairment. EAO is characterised by interstitial cell infiltrate of lymphomonocytes, producers of pro-inflammatory cytokines involved in germ cell apoptosis. Nitric oxide (NO), a free radical promoting immune cell activation and apoptosis, is synthesised by conversion of l-arginine to l-citrulline catalysed by NO synthase (NOS). The NOS isoforms are: constitutively endothelial (e) and neuronal (n) NOS and inducible (i) NOS. OBJECTIVES: Although the NO-NOS system was found to be up-regulated by pro inflammatory mediators in immune and non immune testicular cells, data on its regulation in chronic inflammatory states is lacking. METHODS AND RESULTS: EAO was induced in rats by active immunisation with spermatic antigens and adjuvants; control (C) rats were injected with adjuvants. Untreated normal (N) rats were also studied. We demonstrated that iNOS, eNOS and nNOS was mainly expressed by interstitial cells in N and C rats and that in EAO NOS was up-regulated and also expressed by tubular cells. Constitutive and inducible NOS content (Western blot) as well as NO production and activity increased in the testis of rats with EAO. iNOS content and activity were selectively up-regulated in the testis of rats with orchitis. Flow cytometric analysis of NOS isoforms in testicular macrophages (M) showed that the percentage of ED1(+)ED2(-) and ED1(+)ED2(+) M subsets, expressing constitutive and iNOS isoforms was significantly higher in EAO, but no change in the percentage of ED1(-)ED2(+) resident M was observed compared to C rats. M from EAO rats also released more NO than C and N rats. CONCLUSIONS: In testis of rats with EAO, NO-NOS system was up-regulated and both testicular M and cells from seminiferous tubules contributed to NO increase. NO over production in orchitis was generated mainly by increased iNOS content and activity. PMID- 22672992 TI - Mixed neuroendocrine carcinoma of the gallbladder. PMID- 22672991 TI - Foxp3+CD25(high) CD4+ regulatory T cells from indeterminate patients with Chagas disease can suppress the effector cells and cytokines and reveal altered correlations with disease severity. AB - Immunoregulatory mechanisms are important to control the intense immune activity induced in Chagas disease. We evaluated the phenotypic profile and the mechanisms by which Treg cells function in patients with the indeterminate (IND) and cardiac (CARD) clinical forms of Chagas disease. The frequency of Foxp3(+)CD25(high) CD4(+)-T cells is augmented and correlated with the maintenance of a better cardiac function in IND. Treg cells from IND present suppressive activity, although the mechanism is not IL-10 or CTLA-4 dependent and are able to produce augmented levels of IL-17, IL-10 and granzyme B being its frequency correlated with percentage of Annexin V(+) CD4(+)-cells. In contrast, CARD presents higher frequency of IL-6(+), IFN-gamma(+), TNF-alpha(+) and CTLA-4(+) Treg-cells than IND. Thus, our data suggest that Treg cells have an important role in controlling the exacerbated immune response and morbidity in Trypanosoma cruzi infection, probably modulating the cytokine environment and/or killing effector cells. PMID- 22672993 TI - Relevance of assisted hatching in an oocyte donation programme using egg cryobanking: a prospective randomised study. AB - OBJECTIVE: The objective of this prospective randomised study was to evaluate if there is an improvement in clinical outcomes when assisted hatching (AH) is performed in embryos derived from vitrified/warmed oocytes in an ovum donation programme using egg cryobanking. STUDY DESIGN: Sixty oocyte recipients in a donation programme using egg cryobanking were randomly allocated to the assisted hatched (AH, n=30) or control group (n=30). The pregnancy and implantation rates were compared between the groups. RESULTS: A total of 288 vitrified oocytes were warmed for the 60 recipients. Of the 288 vitrified oocytes, 94.8% survived. All surviving oocytes were sperm injected, and 83.5% underwent fertilisation. There were 172 good-quality embryos selected for transfer. The total pregnancy rate was 40%. The pregnancy rate did not differ between the AH and control groups (43.3% and 33.3%, respectively, p=0.1967), but AH resulted in a higher implantation rate (31.6% vs. 18.4%, p=0.0206). CONCLUSION: Our study demonstrates the effectiveness of AH in embryos derived from warmed oocytes. Our results also suggest that oocyte cryopreservation can be considered as a tool for providing highly successful outcomes in an egg donor programme. PMID- 22672994 TI - Preoperative management of patients with gynecologic malignancy complicated by existing venous thromboembolism. AB - OBJECTIVES: In treating gynecologic malignancies, we sometimes encounter patients in whom venous thromboembolism (VTE) has developed before surgery. Few reports exist on preoperative management of VTE. We conducted a study to determine the optimum preoperative management strategy for patients with gynecologic malignancy and existing VTE. STUDY DESIGN: We reviewed the clinical records of patients treated between April 2004 and March 2010 in the Department of Obstetrics and Gynecology at Mie University Hospital. During this period, 654 exploratory or therapeutic laparotomies were performed for gynecologic malignancy. All patients were assessed by ultrasound for VTE before and after surgery. Twenty-five of the 654 patients (3.8%) had preoperative VTE. We reviewed the 25 cases and evaluated the management method and outcomes in terms of VTE. RESULTS: Most preoperative VTEs were located in a crural vein (23 cases; 92%); only 2 (8%) were in a pelvic vein. Three patients were excluded from the study because they had only a small organized thrombus and were treated with VTE prophylaxis according to American College of Chest Physicians (ACCP) guidelines. The other 22 patients were given graduated compression stockings and began anticoagulation therapy with heparin (unfractionated heparin or heparin calcium) immediately after the VTE diagnosis. Anticoagulation therapy was continued until a mean 8.5h before surgery and then restarted 10h (mean) after surgery. Sixteen of the 22 patients were treated by intermittent pneumatic compression during and after surgery. This management strategy resulted in six cases (27%) of diminished VTE, 10 cases (46%) without remarkable change, and six cases (27%) of deterioration. Clinical deterioration occurred in two of the 22 cases (9%), i.e., PE or pelvic VTE developed. CONCLUSIONS: Our preoperative management of existing VTE appears to be insufficient. Shorter or no interruption of antithrombotic therapy and/or another intervention such as inferior vena cava filter placement may be necessary in patients with preoperative VTE. PMID- 22672995 TI - Establishment and characterization of human peripheral nerve microvascular endothelial cell lines: a new in vitro blood-nerve barrier (BNB) model. AB - The blood-nerve barrier (BNB) is a highly specialized unit that maintains the microenvironments of the peripheral nervous system. Since the breakdown of the BNB has been considered a key step in autoimmune neuropathies such as Guillain Barre syndrome and chronic inflammatory demyelinating polyraduculoneuropathy, it is important to understand the cellular properties of the peripheral nerve microvascular endothelial cells (PnMECs) which constitute the BNB. For this purpose, we established an immortalized cell line derived from human PnMECs. The human PnMECs were transduced with retroviral vectors encoding the temperature sensitive SV40 large T antigen and human telomerase. This cell line, termed FH BNB, showed a spindle fiber-shaped morphology, expression of von Willebrand factor and uptake of acetylated low density lipoprotein. These cells expressed tight junction proteins including occludin, claudin-5, ZO-1 and ZO-2 at the cell cell boundaries. P-glycoprotein and GLUT-1 were also detected by a Western blot analysis and the cells exhibited the functional expression of p-glycoprotein. In addition, transendothelial electrical resistance experiments and paracellular permeabilities of sodium fluorescein and fluorescein isothiocyanate-labeled dextran of molecular weight 4 kDa across these cells demonstrated that FH-BNBs had functional tight junctions. These results indicated that FH-BNBs had highly specialized barrier properties and they might therefore be a useful tool to analyze the pathophysiology of various neuropathies. PMID- 22672996 TI - ABL1 joins the cadre of spindle orientation machinery. AB - Directing the axis of cell division toward extrinsic and intrinsic cues plays a fundamental role in morphogenesis, asymmetric cell division, and stem cell self renewal. Recent studies highlight the misorientation of the cell division axis as a cause of mammalian diseases, including polycystic kidney disease. Although the core regulators for oriented cell division have been identified in invertebrate model systems, we still have an imprecise picture of the relevant signaling networks in the mammalian system. The reasons for this include the lack of established approaches in mammalian cells to survey the molecules required for the spindle orientation. Here we summarize our recent study on a genome-scale RNA mediated interference screen of human kinases to identify a new player for the oriented cell division in both culture cells and developing mammalian tissues. PMID- 22672997 TI - Adult height and risk of coronary heart disease: Tehran Lipid and Glucose Study. AB - BACKGROUND: We assessed the relationship between height and coronary heart disease (CHD) in an urban population of Tehran. METHODS: 4110 participants of the Tehran Lipid and Glucose Study who were 40 years of age or older (1880 men and 2230 women; mean age, 55.1 and 53.0 years, respectively) and free of CHD at baseline were followed for a mean of 9.1 years. We used Cox proportional hazards regression to evaluate the risk of a first CHD event across height tertiles. RESULTS: First CHD events occurred in 239 men and 172 women. The estimated crude HR (95% CI) for CHD events associated with an increment of 1 SD in height was 0.96 (0.28-3.33) in men and 0.84 (0.72-0.97) in women. After adjustment for age, the associations were no longer present. Further adjustment for other confounders had little impact on the results: the HR (95% CI) associated with an increase of 1 SD in height was 1.02 (0.87-1.20) in men and 0.82 (0.66-1.02) in women. CONCLUSIONS: After adjustment for age, height was not associated with CHD incidence in men or women. PMID- 22672998 TI - Relationship between body mass index at age 3 years and body composition at age 11 years among Japanese children: the Shizuoka population-based study. AB - BACKGROUND: A few studies reported an association between body weight during early childhood and body composition in later life, as measured by dual-energy X ray absorptiometry (DXA); however, none of those studies investigated an East Asian population. In a Japanese population, we examined the association between body weight at age 3 years and body composition at age 11 years, as measured using DXA. METHODS: The source population was 726 fifth-grade school children enrolled at 3 public schools in Shizuoka Prefecture, Japan from 2008-2010. All children who lived in the study area went to 1 of these 3 schools. DXA was used to obtain data on body composition, and the Maternal and Child Health Handbook was used to calculate body mass index (BMI). The general linear model was used for statistical analysis. RESULTS: We were able to analyze data on body composition at age 11 years and BMI in early childhood for 550 children. BMI at age 3 and change in BMI z-score from birth to age 3 were positively associated with bone mineral content (BMC), fat-free soft tissue mass (FFSTM), and fat mass (FM) at age 11. After adjusting for confounding factors, mean BMC, FFSTM, and FM were significantly lower among children who were underweight at age 3 and significantly higher among children who were overweight at age 3, as compared with values for normal-weight children at age 3. CONCLUSIONS: Among Japanese children, body weight at age 3 years predicts body composition at age 11 years. PMID- 22672999 TI - Which domain of self-rated health best predicts medical care utilization among Taiwanese adults? AB - BACKGROUND: We attempted to identify the domain of self-rated health (SRH) that best predicts medical care utilization among Taiwanese adults. In addition, we examined the association between SRH and different measure of medical care utilization. METHODS: We analyzed data on 11 987 community-dwelling adults aged 18 to 64 years from the 2005 Taiwan National Health Interview Survey (NHIS). NHIS data were linked to the 2006 National Health Insurance (NHI) administrative database. Then, medical care utilization in 2006, including all outpatient visits, hospitalizations, and mental health outpatient visits, was identified. Domain-specific health ratings were measured by using the Short Form-36 (SF-36) health survey questionnaire. Negative binominal models were used to estimate the contribution of the health domains to medical care utilization. Incidence rate ratios (IRRs) are presented. RESULTS: The IRR for the physical component scale showed that those with the highest scores had 77% of the outpatient visits of those with the lowest scores. The importance of mental health domains was markedly higher in estimating mental health outpatient visits. Those with mental health scores above the median had only 61% of mental health outpatient visits of those with scores below the median. CONCLUSIONS: A person's medical care utilization is reflected in the different domains of general health. Domain specific measures of subjective health are not interchangeable with global general health ratings, because different domains have independent effects on medical care utilization. Our results are potentially important for medical resource allocation because they identify different health domain experiences that require improvement. PMID- 22673001 TI - Atomic force microscopy: a nanoscopic view of microbial cell surfaces. AB - The atomic force microscope (AFM) is a powerful instrument for microbiological investigation. It has evolved from an imaging tool used to investigate microbial surfaces at high resolution in their physiological environment into a lab-on-a tip device, which allows more quantitative analysis of biological samples (from molecules to cells) in aqueous liquids. Atomic force microscopy provides information about the nanoscale architecture of microbes and about the localization and interactions of their individual constituents. Microbial interactions play essential roles in biology, medicine, ecology, biotechnology, food science and contribute to phenomena as varied as bacterial infections, biofilm formation, and bacterial adhesion to surfaces. In this review, we focus on recent developments offered by the rapid advances in AFM imaging and force spectroscopy with emphasizes on microbial research. PMID- 22673000 TI - Youth risk behavior surveillance - United States, 2011. AB - PROBLEM: Priority health-risk behaviors, which are behaviors that contribute to the leading causes of morbidity and mortality among youth and adults, often are established during childhood and adolescence, extend into adulthood, and are interrelated and preventable. REPORTING PERIOD COVERED: September 2010-December 2011. DESCRIPTION OF THE SYSTEM: The Youth Risk Behavior Surveillance System (YRBSS) monitors six categories of priority health-risk behaviors among youth and young adults: 1) behaviors that contribute to unintentional injuries and violence; 2) tobacco use; 3) alcohol and other drug use; 4) sexual behaviors that contribute to unintended pregnancy and sexually transmitted diseases (STDs), including human immunodeficiency virus (HIV) infection; 5) unhealthy dietary behaviors; and 6) physical inactivity. In addition, YRBSS monitors the prevalence of obesity and asthma. YRBSS includes a national school-based Youth Risk Behavior Survey (YRBS) conducted by CDC and state and large urban school district school based YRBSs conducted by state and local education and health agencies. This report summarizes results from the 2011 national survey, 43 state surveys, and 21 large urban school district surveys conducted among students in grades 9-12. RESULTS: Results from the 2011 national YRBS indicated that many high school students are engaged in priority health-risk behaviors associated with the leading causes of death among persons aged 10-24 years in the United States. During the 30 days before the survey, 32.8% of high school students nationwide had texted or e-mailed while driving, 38.7% had drunk alcohol, and 23.1% had used marijuana. During the 12 months before the survey, 32.8% of students had been in a physical fight, 20.1% had ever been bullied on school property, and 7.8% had attempted suicide. Many high school students nationwide are engaged in sexual risk behaviors associated with unintended pregnancies and STDs, including HIV infection. Nearly half (47.4%) of students had ever had sexual intercourse, 33.7% had had sexual intercourse during the 3 months before the survey (i.e., currently sexually active), and 15.3% had had sexual intercourse with four or more people during their life. Among currently sexually active students, 60.2% had used a condom during their last sexual intercourse. Results from the 2011 national YRBS also indicate many high school students are engaged in behaviors associated with the leading causes of death among adults aged >= 25 years in the United States. During the 30 days before the survey, 18.1% of high school students had smoked cigarettes and 7.7% had used smokeless tobacco. During the 7 days before the survey, 4.8% of high school students had not eaten fruit or drunk 100% fruit juices and 5.7% had not eaten vegetables. Nearly one-third (31.1%) had played video or computer games for 3 or more hours on an average school day. INTERPRETATION: Since 1991, the prevalence of many priority health-risk behaviors among high school students nationwide has decreased. However, many high school students continue to engage in behaviors that place them at risk for the leading causes of morbidity and mortality. Variations were observed in many health-risk behaviors by sex, race/ethnicity, and grade. The prevalence of some health-risk behaviors varied substantially among states and large urban school districts. PUBLIC HEALTH ACTION: YRBS data are used to measure progress toward achieving 20 national health objectives for Healthy People 2020 and one of the 26 leading health indicators; to assess trends in priority health-risk behaviors among high school students; and to evaluate the impact of broad school and community interventions at the national, state, and local levels. More effective school health programs and other policy and programmatic interventions are needed to reduce risk and improve health outcomes among youth. PMID- 22673002 TI - pH regulators in invadosomal functioning: proton delivery for matrix tasting. AB - Invadosomes are actin-rich finger-like cellular structures sensing and interacting with the surrounding extracellular matrix (ECM) and involved in its proteolytic remodeling. Invadosomes are structures distinct from other adhesion complexes, and have been identified in normal cells that have to cross tissue barriers to fulfill their function such as leukocytes, osteoclasts and endothelial cells. They also represent features of highly aggressive cancer cells, allowing them to escape from the primary tumor, to invade surrounding tissues and to reach systemic circulation. They are localized to the ventral membrane of cells grown under 2-dimensional conditions and are supposed to be present all around cells grown in 3-dimensional matrices. Indeed invadosomes are key structures in physiological processes such as inflammation and the immune response, bone remodeling, tissue repair, but also in pathological conditions such as osteopetrosis and the development of metastases. Invadosomes are subdivided into podosomes, found in normal cells, and into invadopodia specific for cancer cells. While these two structures exhibit differences in organization, size, number and half-life, they share similarities in molecular composition, participation in cell-matrix adhesion and promoting matrix degradation. A key determinant in invadosomal function is the recruitment and release of proteases, such as matrix metalloproteinases (MMPs), serine proteases and cysteine cathepsins, together with their activation in a tightly controlled and highly acidic microenvironment. Therefore numerous pH regulators such as V-ATPases and Na(+)/H(+) exchangers, are found in invadosomes and are directly involved in their constitution as well as their functioning. This review focuses on the participation of pH regulators in invadosome function in physiological and pathological conditions, with a particular emphasis on ECM remodeling by osteoclasts during bone resorption and by cancer cells. PMID- 22673003 TI - A vibrational technique for diagnosing loosened total hip endoprostheses: an experimental sawbone study. AB - Aseptic loosening of hip implants is a severe orthopaedic problem and a valid diagnosis is often difficult. A potential method to determine loosening of the prosthesis is a swing analysis of the bone-implant interface using a vibrational technique. In this study, hip models were constructed to assess the vibration behaviour of the stem and cup components. Four different states of implant loosening were simulated: (1) stem and cup stable, (2) stem loosened and cup stable, (3) stem and cup loosened, and (4) stem stable and cup loosened. The model was excited at the lateral condyle of the femur between 100 Hz and 2000 Hz. Resonance spectra were recorded using an optical laser vibrometer and an accelerometer-based system. Analysis of the spectra revealed shifts of the resonances towards lower frequencies, especially in the case of a loosened stem component. The integral value of the spectra was a second parameter that was sensitive to a stem loosening. In the case of a loosened cup, a peak count analysis resulted in a significantly higher number of counts. In our model, different states of implant loosening could be determined with a vibrational technique and the localisation of the loosened component could be distinguished as well. PMID- 22673004 TI - Dynamic properties of human round window membrane in auditory frequencies running head: dynamic properties of round window membrane. AB - Round window is one of the two openings into cochlea from the middle ear. Mechanical properties of round window membrane (RWM) affect cochlear fluid motion and play an important role in the transmission of sound into cochlea. However, no measurement of mechanical properties of RWM has been reported because of the complication of its location and small size. This paper reports the first investigation on dynamic properties of human RWM using acoustic stimulation and laser Doppler vibrometry measurement. The experiments on RWM specimens were subsequently simulated in finite element (FE) model and an inverse-problem solving method was used to determine the complex modulus in frequency-domain and the relaxation modulus in time-domain. The results show that the average storage modulus of human RWM changes from 2.32 to 3.83 MPa and the average loss modulus from 0.085 to 0.925 MPa over frequencies of 200-8000 Hz. The effects of specimen geometry and experimental condition on complex modulus measurements were discussed through FE modeling analysis. Dynamic properties of RWM reported in this paper provide important data for the study of middle ear and cochlear mechanics. PMID- 22673005 TI - A combination of thermal methods to assess coronary pressure and flow dynamics with a pressure-sensing guide wire. AB - Measurement of coronary pressure and absolute flow dynamics have shown great potential in discerning different types of coronary circulatory disease. In the present study, the feasibility of assessing pressure and flow dynamics with a combination of two thermal methods, developed in combination with a pressure sensor-tipped guide wire, was evaluated in an in vitro coronary model. A continuous infusion thermodilution method was employed to determine the average flow, whereas a thermal anemometric method was utilized to assess the pressure and flow dynamics, simultaneously. In the latter method, the electrical power supplied to an element, kept at constant temperature above ambient temperature, was used as a measure for the shear rate. It was found that, using a single calibration function, the method was able to assess coronary pressure and flow dynamics for different flow amplitudes, heart rates, and different pressure wires. However, due to the fact that the thermal anemometric method cannot detect local shear rate reversal, the method was unable to reliably measure flow dynamics close to zero. Nevertheless, the combined methodology was able to reliably assess diastolic hemodynamics. The diastolic peak flow and average diastolic resistance could be determined with a small relative error of (8 +/- 7)% and (7 +/- 5)%, respectively. PMID- 22673006 TI - Re: Xiao-Dong Jin, Simone Roethlisberger, Fiona C. Burkhard, Frederic Birkhaeuser, Harriet C. Thoeny, Urs E. Studer. Long-term renal function after urinary diversion by ileal conduit or orthotopic ileal bladder substitution. Eur Urol 2012;61:491-7. PMID- 22673007 TI - Treatment of overactive bladder with botulinum toxin: are there more challenges to deal with? PMID- 22673008 TI - Allometric study on the relationship between the growth of ovarian follicles and oocytes in domestic cats. AB - The relationship between the growth of preantral and antral follicles and that of their oocytes in ovaries of domestic cats (Felis catus) was analyzed. Eight hundred and five pairs of follicles and oocytes from the ovaries of 51 female cats were collected, and only healthy and fresh follicles and oocytes with or without zona pellucida were used in this study. Immediately after collection, the diameters of follicles and their oocytes were measured. The relationship of the follicle diameter to the oocyte diameter was applied to four regression models and statistically analyzed. The best fitting model was found to be a hyperbolic regression (the coefficient of determination was 0.976 between the follicles and their oocytes with a zona pellucida, y=184x/(x+0.0738); the coefficient of determination was 0.983 between the follicles and their oocytes without a zona pellucida, y=122x/(x+0.0301)). The differentiated equations for the hyperbolic curves in the oocytes with or without a zona pellucida and the follicles were found to be y'=13.6/(x+0.0738)2 and y'=3.67/(x+0.0301)2, where y and x were the diameters of the oocytes (MUm) and follicles (mm), respectively. When follicles grew to a size larger than 0.4 mm in diameter, the growth rates of their oocytes calculated by the differentiation equations showed an asymptotic depression around zero. Thus, it was suggested that when the follicles grew to a size larger than 0.4 mm in diameter, their oocytes reached full size and ceased to grow and that the zona pellucida stopped growing when the diameter of the follicles reached 0.3 mm in domestic cats. PMID- 22673009 TI - Mechanisms of CYP3A induction by glucocorticoids in human fetal liver cells. AB - Human fetal liver (HFL) cells express major drug metabolic enzymes CYP3A4, CYP3A5 and CYP3A7. In the fetal hepatocytes, betamethasone and dexamethasone (DEX) markedly enhanced the expression levels of CYP3A4 and CYP3A7 mRNAs and slightly increased the expression level of CYP3A5 mRNA. Interestingly, a high correlation between the CYP3A induction ability and the intensity of anti-inflammatory effect was observed. Human glucocorticoid receptor (GR)-small interfering RNA clearly attenuated the expression level of GR mRNA, and diminished the DEX-stimulated CYP3A4, CYP3A5 and CYP3A7 expression in HFL cells. These findings indicate that GR mediates the induction of CYP3A4 and CYP3A7 expression in human fetal hepatocytes as well as the CYP3A5. PMID- 22673010 TI - Changes in CYP1A2 activity in humans after 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) administration using caffeine as a probe drug. AB - 3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) is a ring-substituted amphetamine widely used for recreational purposes. MDMA is predominantly O demethylenated in humans by cytochrome P450 (CYP) 2D6, and is also a potent mechanism-based inhibitor of the enzyme. After assessing the inhibition and recovery of CYP2D6 in a previous study, the aim of this work was to study in humans the activity of CYP1A2 in vivo after CYP2D6 had been inhibited by MDMA, using caffeine as a probe drug. Twelve male and nine female recreational MDMA users were included. In session 1, 100 mg of caffeine was given at 0 h. In session 2, a 1.5 mg/kg MDMA dose (range 75-100 mg) was given at 0 h followed by a 100 mg dose of caffeine 4 h later. Aliquots of plasma were assayed for caffeine (137X) and paraxanthine (17X) and statistically significant differences were assessed with a one-way ANOVA. There were significant gender differences at basal condition, which persisted after MDMA administration. CYP1A2 activity was higher in both genders after drug administration, with an increase in 40% in females and 20% in males. Results show an increase in CYP1A2 activity when CYP2D6 is inhibited by MDMA in both genders, being more pronounced in females. PMID- 22673011 TI - Different truncation methods of AUC between Japan and the EU for bioequivalence assessment: influence on the regulatory judgment. AB - In regulatory guidelines for bioequivalence (BE) assessment, the definitions of AUC for primary assessment are different in ICH countries, i.e., AUC from zero to the last sampling point (AUCall) in Japan, AUC from zero to infinity (AUCinf) or AUC from zero to the last measurable point (AUClast) in the US, and AUClast in the EU. To assure sufficient accuracy of truncated AUC for BE assessment, the ratio of truncated AUC (AUCall or AUClast) to AUCinf should be more than 80% both in Japanese and EU guidelines. We investigated how the difference in the definition of truncated AUC affects BE assessment of sustained release (SR) formulation. Our simulation result demonstrated that AUCall/AUCinf could be >=80% despite AUClast/AUCinf being <80% and AUCall failed to detect formulation difference. In Japanese package inserts of generic drugs in SR formulation, there were products for which AUCall/AUCinf was >=80% though AUClast/AUCinf was <80%. In conclusion, it was confirmed that the difference in definition of truncated AUC affected the judgment of validity of truncated AUC for BE assessment, and AUCall could fail to detect the substantially different in vivo dissolution profile of generic drugs with SR formulation from the original drug. PMID- 22673012 TI - Resveratrol-sensitized UVA induced apoptosis in human keratinocytes through mitochondrial oxidative stress and pore opening. AB - Resveratrol (3,5,4'-trihydroxy-trans-stilbene), a polyphenol compound, is derived from natural products such as the skin of red grapes, blueberries and cranberries. Resveratrol not only exhibits antioxidant, cardioprotection, and anti-aging properties, but can also inhibit cancer cell growth and induce apoptosis. It has been shown that resveratrol inhibits the activation of Nf kappaB and subsequently down regulates the expression of Nf-kappaB regulated genes such as interleukin-2 and Bcl-2, leading to cell cycle arrest and increased apoptosis in multiple myeloma cells. In the skin, resveratrol has been reported to sensitize keratinocytes to UVA induced apoptosis. However, the effect of resveratrol on opening of the mitochondrial permeability transition pore has not been previously examined. Our data show that UVA (14 J/cm(2)) along with resveratrol causes massive oxidative stress in mitochondria. As a consequence of oxidative stress, the mitochondrial membrane potential decreases which results in opening of the mitochondrial pores ultimately leading to apoptosis in human keratinocytes. These results may have clinical implications for development of future chemotherapeutic treatment for tumors of the skin. PMID- 22673013 TI - Photocatalytic degradation of toluene using sprayed N-doped ZnO thin films in aqueous suspension. AB - Thin films of N-doped ZnO are synthesized via spray pyrolysis technique in aqueous medium using zinc acetate and ammonium acetate as precursors. Influence of N doping onto photochemical, structural, morphological, optical and thermal properties have been investigated. Structural analysis depicts hexagonal (wurtzite) crystal structure. The effect of N doping on the photocatalytic activity of N-doped ZnO in the degradation of toluene is studied and results are compared with pure ZnO. The results show that the rate of degradation of toluene over N-doped ZnO is higher as compared to that of pure ZnO and increases with increasing N doping up to 10 at.% and then decreases. The enhancement of photocatalytic activity of N-doped ZnO thin films is mainly due to their capability for reducing the electron hole pair recombination. The photocatalytic mineralization of toluene in aqueous solution has been studied by measuring COD and TOC. Possible reaction mechanism pathways during toluene degradation over N doped ZnO has been proposed. PMID- 22673014 TI - Evaluation of interparticle interaction between colloidal Ag nanoparticles coated with trisodium citrate and safranine by using FRET: spectroscopic and mechanistic approach. AB - Current study employs fluorescence spectroscopy, UV-Vis absorbance spectroscopy, dynamic light scattering (DLS) and cyclic voltammetry (CV) to investigate the interaction of safranine dye with spherical shaped silver nanoparticles (AgNPs) coated with trisodium citrate. In fluorescence spectroscopic study we used the AgNPs and safranine dye as component molecules for the construction of FRET, whereas AgNPs serve as donor fluorophore and safranine as acceptor. The fluorescence quenching of AgNPs followed by sensitization of safranine occurs almost simultaneously by addition of safranine dye with different concentrations, indicating fluorescence energy transfer observed between them. Interaction between safranine and AgNPs is also confirmed by using UV-Vis absorption spectroscopy. Addition of safranine results in the significant decrease in the absorbance of AgNPs at 423 nm and simultaneous increase in the absorbance of safranine at 518, 276 and 248 nm which is indication of rapid binding of safranine molecules with AgNPs. However CV measurements reveals that the safranine molecule does not alter the redox properties of the AgNPs but the safranine molecule lose their redox properties upon getting bonded with AgNPs. This clearly confirms that the safranine molecules get attached on the surface of AgNPs which was also supported by the DLS as well as zeta potential measurement. PMID- 22673015 TI - Factors associated with glomerular hyperfiltration in the early stage of hypertension. AB - BACKGROUND: Glomerular hyperfiltration predicts development of nephropathy in hypertension but the factors responsible for increased glomerular filtration rate (GFR) are not well known. Aim of this study was to examine which clinical variables influence GFR in the early stage of hypertension. METHODS: Participants were 1,106 young-to-middle-age hypertensive adults with creatinine clearance >60 ml/min/1.73 m(2). Clinic and ambulatory blood pressures (BPs) were measured and the difference between clinic and 24-h systolic BP was defined as the white-coat effect (WCE). In 606 participants, 24-h urinary epinephrine and norepinephrine were also measured. Glomerular hyperfiltration, defined as a GFR >=150 ml/min/1.73 m(2), was present in 201 subjects. RESULTS: Patients' mean age was 33.1 +/- 8.5 years and office BP was 146 +/- 10.5/94 +/- 5.0 mm Hg. In multivariable linear regression, significant predictors of GFR were younger age (P < 0.0001), male gender (P < 0.0001), 24-h systolic BP (P = 0.0001), body mass (P < 0.0001), WCE (P = 0.02), log-epinephrine (P = 0.01), and coffee use (P < 0.01). In a logistic model, independent predictors of glomerular hyperfiltration were obesity (odds ratio, 95% confidence interval = 6.1, 3.8-9.8), male gender (2.9, 1.8-4.9), age <33 years (2.1, 1.5-3.1), ambulatory hypertension (2.0, 1.4 3.0), WCE >15 mm Hg (1.6, 1.1-2.3), heavy coffee use (2.0, 1.1-3.8), and epinephrine >25 mcg/24 h (1.9, 1.2-3.1). CONCLUSIONS: The novel finding of this study is that hyper-reactivity to stress, as determined by urinary epinephrine level and WCE, and coffee use contribute to determining glomerular hyperfiltration in the early stage of hypertension. Our data may help to identify a subset of patients with glomerular hyperfiltration, who may be at increased risk of chronic kidney disease and may benefit from antihypertensive treatment. PMID- 22673016 TI - Parental blood pressure is related to vascular properties of their 5-year-old offspring. AB - BACKGROUND: Adolescent offspring of hypertensive parents have increased carotid intima media thickness (CIMT) and arterial stiffness compared with offspring of normotensives. We assessed whether systolic blood pressure (SBP) of both parents is associated with the vasculature of their offspring as early as in childhood. METHODS: In the first 306 5-year-old children of the Wheezing-Illnesses-Study Leidsche-Rijn birth cohort, CIMT, distensibility, and elastic modulus (EM) were obtained ultrasonographically. In 204 of 306 (67%) children, complete data on both maternal and paternal SBP were obtained from the linked database of the Utrecht Health Project. RESULTS: CIMT of the children was 0.58 um (95% confidence interval (CI): 0.14, 1.0) greater with every 1-mm Hg higher maternal SBP. Maternal SBP and children's distensibility and EM were more strongly associated, negative and positive respectively, with increasing paternal SBP and vice versa (P value-for-interaction: 0.003 and 0.001, respectively). CIMT of children of whom both parents were in the highest SBP tertile was 17.9 um (95% CI: 4.0, 31.9) greater compared with the CIMT of children of whom neither one of the parents had a SBP in the highest tertile. For EM and distensibility, these estimates were 20.1 kPa (95% CI: 1.1, 39.2) and -11.6 1/Mpa (95%-CI: -22.9, -0.31), respectively. CONCLUSIONS: Higher maternal SBP is related to thicker arterial walls in their 5-year-old offspring. If both parents have higher SBP, the arterial wall of their offspring is thicker and stiffer. PMID- 22673017 TI - Tetrahydrobiopterin supplementation enhances carotid artery compliance in healthy older men: a pilot study. AB - BACKGROUND: We performed a pilot study to test the hypothesis that acute oral ingestion of tetrahydrobiopterin (BH(4)), a key cofactor modulating vascular nitric oxide (NO) synthase activity, improves large elastic artery stiffness with aging in men. METHODS: Healthy older (63 +/- 2 years; n = 8) and young (age 25 +/ 1 years; n = 6) men were studied 3 h after ingestion of BH(4) (10 mg.kg(-1) body weight) or placebo on separate days in a randomized, placebo-controlled, double blind study. RESULTS: Baseline carotid artery compliance was 37% lower (0.17 +/- 0.02 vs. 0.22 +/- 0.02 mm/mm Hg.10(-1)) and beta-stiffness was 42% higher (7.3 +/ 1.1 vs. 4.2 +/- 0.5 AU) in the older men (both P < 0.05). BH(4) ingestion markedly increased circulating BH(4) concentrations in both groups (17-19-fold, P < 0.05), but increased compliance (+39% to 0.23 +/- 0.02 mm/mm Hg.10(-1), P < 0.01) and decreased beta-stiffness index (-27% to 5.3 +/- 0.7 AU, P < 0.01) only in the older men. BH(4) also reduced carotid systolic blood pressure (SBP) in the older men (P < 0.05). CONCLUSIONS: These preliminary results support the possibility that limited BH(4) bioavailability contributes to impaired carotid artery compliance in healthy older men. Further studies are needed to determine if increasing BH(4) bioavailability though oral BH(4) supplementation may have therapeutic efficacy for improving large elastic artery compliance and reducing central SBP with aging. PMID- 22673018 TI - The relationship between objectively measured physical activity, sedentary time, and vascular health in children. AB - BACKGROUND: Physical activity (PA) is beneficially associated with arterial compliance in adults; however, whether this association persists in children is unclear. We examined the cross-sectional relationship of PA and sedentary time with arterial compliance in children. METHODS: Large and small artery compliance was determined by diastolic pulse contour analysis in 102 children aged 8-11 years (43 boys). We used accelerometers and age-specific cut points to classify activity as sedentary, light, or moderate-to-vigorous (MVPA). We also categorized MVPA according to bout length (0-5, 5-10, 10-20, and >=20 min). Hierarchical linear regression examined: (i) the contribution of activity to large and small artery compliance (controlling for body surface area, systolic blood pressure, and body mass index (BMI)) and (ii) whether bouted MVPA was associated with arterial compliance independent of total MVPA. RESULTS: Activity variables did not explain any additional variance in large artery compliance beyond that captured by body surface area, BMI, and systolic blood pressure (P = 0.118 to P = 0.990). Light activity and MVPA explained an additional 5.8% (P = 0.003) and 2.7% (P = 0.043) of the variance in small artery compliance. MVPA accumulated in bouts was not significantly associated with small artery compliance after controlling for the total volume of MVPA (P = 0.784 to P = 0.923). CONCLUSIONS: Objectively measured PA is associated with small, but not large artery compliance in children aged 8-11 years. Future research should explore the influence of bout frequency and the effect of a PA.intervention on arterial compliance. PMID- 22673019 TI - The great East Japan earthquake: blood pressure control in patients with chronic kidney disease. AB - BACKGROUND: At 1446 on 11 March 2011, northeastern Japan was struck by a major earthquake measuring 9.0 on the Richter scale. There have been several reports of transient blood pressure increases after a major earthquake, but the impact of a major earthquake on blood pressure in chronic kidney disease (CKD) patients has not been fully investigated. METHODS: Changes in clinic blood pressure following the earthquake were investigated in 132 hypertensive patients with stage 3 and 4 CKD who were residents of Fukushima City. RESULTS: Both systolic and diastolic blood pressures were significantly elevated 1-3 weeks after the earthquake compared with before the earthquake (134 +/- 19 mm Hg vs. 138 +/- 20 mm Hg, P = 0.02 for systolic; 76 +/- 13 mm Hg vs. 79 +/- 12 mm Hg, P = 0.01 for diastolic), and these values returned to baseline by 5-7 weeks after the earthquake. Multiple logistic regression analysis identified male sex (odds ratio (OR), 0.35; 95% confidence interval (CI), 0.14-0.86; P = 0.02), mean blood pressure at baseline (OR, 0.92; 95% CI, 0.86-0.96; P < 0.01), and sympatholytic medications, such as alpha-blockers, beta-blockers, or central sympatholytics (OR, 0.23; 95% CI, 0.07 0.76; P = 0.01), as independent factors related to elevation of mean blood pressure 1-3 weeks after the earthquake in CKD patients. CONCLUSIONS: Blood pressure was significantly increased after a major earthquake in hypertensive patients with stage 3 and 4 CKD. During the first 3 weeks after the earthquake, blood pressure control was associated with the use of sympatholytic medications. PMID- 22673020 TI - Home blood pressure level, blood pressure variability, smoking, and stroke risk in Japanese men: the Ohasama study. AB - BACKGROUND: Hypertension and smoking independently contribute to the risk of stroke. Our objective was to investigate home blood pressure (HBP) levels, day-by day BP variability, and smoking in the prediction of stroke in Japanese men. METHODS: In this study, 902 men (mean age, 58.6 years) without a past history of stroke were evaluated. HBP was measured once every morning for 4 weeks. Day-by day BP variability was defined as within-subject standard deviations (SD) of HBP. Smoking history was obtained from a standardized questionnaire. Hazard ratios (HRs) for stroke were examined by Cox regression model, with adjustment for possible confounders. RESULTS: During 13.1 years (median) of follow-up, 89 cerebral infarctions, 28 intracranial hemorrhages, and six other strokes occurred. Systolic HBP levels (HR = 1.59 per 14.6 mm Hg increase, P < 0.0001) and variability (HR = 1.26 per 3.1 mm Hg increase, P = 0.03) of +1 between-subject SD were significantly associated with cerebral infarction. The relationship between HBP and cerebral infarction differed with smoking status (interaction P = 0.021 and 0.017 for systolic level and variability, respectively). In analyses stratified according to smoking, systolic level (HR = 1.78, P < 0.0001) and variability (HR = 1.38, P = 0.006) were significantly associated with cerebral infarction in ever smokers (N = 511), but not in never smokers (N = 391; P >= 0.6 for both). No significant association was found between smoking and the risk of intracranial hemorrhage. CONCLUSIONS: In ever smokers, both HBP levels and variability are significantly associated with the risk of cerebral infarction. Our findings further validate the benefit of smoking cessation in preventing cardiovascular disease (CVD), especially cerebral infarction. PMID- 22673021 TI - Feasibility and reproducibility of noninvasive 24-h ambulatory aortic blood pressure monitoring with a brachial cuff-based oscillometric device. AB - BACKGROUND: Accumulating evidence suggests the potential superiority of office aortic blood pressure (BP) over brachial in the management of arterial hypertension. The noninvasive aortic 24-h ambulatory brachial BP monitoring (ABPM) is potentially the optimal method for assessing BP profile. The objective of the present study was to investigate the feasibility and reproducibility to perform noninvasively 24-h aortic ABPM with a novel validated brachial cuff-based automatic oscillometric device (Mobilo-O-Graph) which records brachial BP and waveforms and assesses aortic BP via mathematical transformation. METHODS: Thirty consecutive subjects (mean age: 53.6 +/- 11.6 years, 17 men) had a test-retest ABPM with at least 1-week interval. No modification of vasoactive drug treatment during the interval was allowed while similar 24-h activity during both recording days was recommended. RESULTS: The average number of valid readings for brachial vs. aortic BP were 69.9 +/- 10.4 vs. 58.0 +/- 13.3 in the initial 24-h assessment (P < 0.001) and 68.3 +/- 10.8 vs. 56.4 +/- 13.6 in the repeat assessment (P < 0.001). No differences in average 24 h aortic BP values were observed between the two assessments (systolic blood pressure (SBP) 115.9 +/- 7.7 vs. 115.1 +/- 6.0 mm Hg, respectively, P = 0.48, and diastolic 79.7 +/- 7.4 vs. 79.2 +/- 8.7, P = 0.54). Reproducibility indices of aortic pressure including, intraclass coefficient of variation (SBP: 0.80 (95% confidence interval 0.58-0.90); diastolic: 0.92 (0.83-0.96)) and s.d. of differences (SBP/diastolic: 6.0/4.5 mm Hg) indicated acceptable reproducibility. The Bland-Altman plots indicated no evidence of systemic bias. CONCLUSIONS: In conclusion, these data suggest that noninvasive 24-h ABPM is feasible and provides reproducible values. Future studies should validate the prognostic ability of 24-h aortic hemodynamics. PMID- 22673022 TI - Left ventricular structure and function in relation to steroid biosynthesis genes in a white population. AB - BACKGROUND: Both endogenous ouabain (EO) and aldosterone are steroid hormones which might play a role in the pathogenesis of left ventricular (LV) hypertrophy and cardiac remodeling. Cholesterol side-chain cleavage enzyme (CYP11A1) and 3beta-hydroxysteroid dehydrogenase (HSD3B1) are two key enzymes in the pathway of steroid biosynthesis. METHODS: We investigated in 532 individuals (mean age, 50.3 years; 51.5% women) randomly recruited from a white European population whether LV structure and function were related to genetic variations in CYP11A1 and HSD3B1. We measured LV structure by conventional echocardiography and LV diastolic function by Doppler imaging of the transmitral blood flow and the mitral annular movement. We genotyped tag single nucleotide polymorphisms (SNPs) rs2279357, rs11638442 and rs2073475 in CYP11A1, and rs2236780, rs3765945, and rs6203 in HSD3B1. RESULTS: While adjusting for covariables and accounting for family clusters, LV mass index decreased (P <= 0.049) across the CYP11A1 genotypes in rs2279357 (CC vs. CT vs. TT), rs11638442 (GG vs. GC vs. CC), and rs2073475 (GG vs. GA+AA). Carriers of the CYP11A1 TCG haplotype had lower (P <= 0.017) LV mass and LV mass index than noncarriers. Carriers of HSD3B1 GCC haplotype had lower peak early (Ea; P = 0.004) and higher peak late (Aa; P = 0.066) diastolic mitral annular velocities and therefore a lower Ea/Aa ratio (P = 0.041) as compared with noncarriers. Neither plasma endogenous ouabain nor 24-h urinary aldosterone were related to any of the SNPs or haplotypes (P >= 0.07). CONCLUSIONS: Pending confirmation in other studies, LV mass and LV diastolic function seem to be related to genetic variation in the steroid biosynthesis. PMID- 22673023 TI - Efficacy of oral tolvaptan in acute heart failure patients with hypotension and renal impairment. AB - AIMS: Although congestion is the main reason for admission in patients with worsening acute heart failure syndromes, patients presenting with low SBP and renal impairment often do not respond adequately to and may not tolerate traditional diuretic therapy. We sought to determine the short-term hemodynamic effects of tolvaptan in this high-risk population. METHODS: In a subset analysis of the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan trial, 759 patients (18% of total) had elevated blood urea nitrogen (BUN) (> 20 mg/dl) and low SBP (<105 mmHg) at admission. Of these, 386 were randomized to tolvaptan and 373 to placebo. RESULTS: Demographics and baseline characteristics were similar in both groups. Greater reductions from baseline in body weight were observed for tolvaptan (1.63 +/- 2.00 vs. 0.76 +/- 1.75 kg, P < 0.0001 at day 1 and 3.23 +/- 3.36 vs. 2.10 +/- 3.47 kg, P < 0.0001 at day 7 or discharge). Greater increases in serum sodium concentration were also observed in the tolvaptan group as early as day 1 (4.41 +/- 3.67 vs. 1.32 +/- 3.93 mEq/l, P < 0.0001) and persisted through day 7 or discharge (4.79 +/- 4.89 vs. 1.25 +/- 5.00 mEq/l, P < 0.0001). Similarly, improvements in patient-reported dyspnea and investigator-assessed orthopnea were significantly greater in the tolvaptan group as early as day 1 of treatment. These changes were not associated with significant differences in heart rate, SBP, DBP or serum creatinine between patients in the two treatment groups during hospitalization. In-hospital mortality rates (total and cause-specific) were comparable to patients who had presented with SBP more than 105 mmHg and BUN less than 20 mg/dl. CONCLUSION: In this subgroup analysis of patients with hypotension and renal impairment, tolvaptan improved symptoms, reduced body weight and increased serum sodium as early as inpatient day 1 without adversely affecting blood pressure or renal function. PMID- 22673024 TI - Coronary plaque quantification and composition in asymptomatic patients with type II diabetes mellitus. AB - OBJECTIVE: The aim of this study was to characterize the extent and morphology of coronary lesions in asymptomatic patients with type II diabetes mellitus. METHODS: We enrolled 102 asymptomatic patients with type II diabetes mellitus and 97 patients without diabetes as controls. All individuals had no history of ischemic heart disease. They underwent multidetector computed tomography (MDCT). Plaque density and plaque volume were calculated using specific software on axial images. Arterial remodeling was evaluated with semiquantitative assessment on image reconstructions. RESULTS: MDCT angiography revealed the presence of 124 coronary plaques in 46 patients with type II diabetes mellitus and 59 plaques in 21 controls (P<0.01). Diabetic patients had a significantly higher proportion of lesions with impaired adaptive remodeling (56.5 versus 35.6%, P<0.01), as compared with nondiabetic individuals. The volume of fibrofatty component was 0.1 cm (0.01-0.72) in diabetic patients and 0.08 cm (0.01-0.33) in controls (P=0.14). The calcium volume was 0.082 cm (0-0.558) in diabetic patients and 0.12 cm (0 0.669) in controls (P=0.21). Plaques with fibrofatty components had a significantly higher density in the diabetic cohort (58.76 +/- 9.55 Hounsfield Units), as compared with the control group (47.31 +/- 5.42 Hounsfield Units, P<0.001). Plaque density correlated with the duration of type II diabetes mellitus (r=0.37, P=0.044), but was independent of age, sex, hypertension and metabolic profile. In the control group, plaque density was independent of any covariate. CONCLUSION: Coronary plaques in type II diabetes mellitus show a tendency to develop impaired adaptive remodeling and to have a higher tissue density. PMID- 22673025 TI - The growing importance of PON1 in cardiovascular health: a review. AB - The wide acceptance of the oxidation theory of atherogenesis has prompted attention to antioxidant mechanisms, particularly the prevention of lipid oxidation by high-density lipoprotein-associated proteins like paraoxonase 1 (PON1) enzyme. PON1 is a calcium-dependent enzyme that has interested toxicologists since its discovery as an organophosphate hydrolase. There is a growing interest in the enzyme's importance in cardiovascular health prompted by evidence that it may have a role in lipid metabolism and the development of atherosclerosis via its antioxidant effects. PON1 is capable of hydrolyzing homocysteine thiolactone, a metabolite of homocysteine that can impair protein function leading to endothelial dysfunction and vascular damage. Although this lactonase activity has been suggested to be PON1's native activity, the enzyme's specific physiological role and substrate remain unclear. In this review, we summarize developments in the field of PON1 research relating to cardiovascular health, and highlight those that perhaps warrant further research. PMID- 22673026 TI - ST-segment elevation during levosimendan infusion. AB - Levosimendan increases the sensitivity of the heart to calcium and consequently exerts positive inotropic effects. Levosimendan is indicated in acutely decompensated severe congestive heart failure. We report that levosimendan infusion may induce myocardial ischemia in patients with acute heart failure. PMID- 22673027 TI - Pathology findings mimicking acute myocardial infarction in a case of Takotsubo cardiomyopathy complicated by cardiac rupture. PMID- 22673028 TI - Survival and retention of the probiotic properties of Bacillus sp. strains under marine stress starvation conditions and their potential use as a probiotic in Artemia culture. AB - The probiotic properties of Bacillus strains isolated from Artemia culture and the effect of marine stress on viability and survival were investigated, as well as the changes occurring in their properties. Analyses showed that these bacteria corresponded to the genus Bacillus sp. Antagonism and adherence assays revealed that Bacillus strains have an inhibitory effect against tested pathogenic bacteria and are fairly adherent. Normal and starved cells showed different enzymatic profiles. Challenge tests performed with Artemia larvae provided evidence that the tested Bacillus strains were neither pathogenic nor toxic to the host and conferred protection for Artemia culture against pathogens. The tested strains maintained their viability and their probiotic properties during the period of study. The results suggest that the tested strains have suffered changes allowing them to survive in seawater in the absence of nutrients and outside their natural host, identifying them as potential probiotic candidates for Artemia culture. PMID- 22673029 TI - Isolation of an acyl-glucose-dependent anthocyanin 7-O-glucosyltransferase from the monocot Agapanthus africanus. AB - A cDNA encoding an acyl-glucose-dependent anthocyanin 7-O-glucosyltransferase (AaAA7GT) was isolated from Agapanthus africanus petals; this is the first AAGT identified in a monocot. Peak expression of AaAA7GT in developing A. africanus petals occurred before the flowering stage, and was later than found previously for other anthocyanin biosynthetic genes. Analysis of recombinant proteins showed AaAA7GT had strict substrate preference for anthocyanidin 3-O-glycosides. The AaAA7GT amino acid had high sequence similarity to glycoside hydrolase family 1 (GH1) proteins, which typically act as beta-glycosidases. A phylogenetic analysis of amino acid sequences suggested that AAGTs were derived from glycosidase early in the angiosperm lineage. PMID- 22673030 TI - Flooding affects uptake and distribution of carbon and nitrogen in citrus seedlings. AB - Soil flooding has been widely reported to affect large areas of the world. In this work, we investigated the effect of waterlogging on citrus carbon and nitrogen pools and partitioning. Influence on their uptake and translocation was also studied through 15N and 13C labeling to provide insight into the physiological mechanisms underlying the responses. The data indicated that flooding severely reduced photosynthetic activity and affected growth and biomass partitioning. Total nitrogen content and concentration in the plant also progressively decreased throughout the course of the experiment. After 36 days of treatment, nitrogen content of flooded plants had decreased more than 2.3-fold compared to control seedlings, and reductions in nitrogen concentration ranged from 21 to 55% (in roots and leaves, respectively). Specific absorption rate and transport were also affected, leading to important changes in the distribution of this element inside the plant. Additionally, experiments involving labeled nitrogen revealed that 15N uptake rate and accumulation were drastically decreased at the end of the experiment (93% and 54%, respectively). 13CO2 assimilation into the plant was strongly reduced by flooding, with delta13C reductions ranging from 22 to 37% in leaves and roots, respectively. After 36 days, the relative distribution of absorbed 13C was also altered. Thus, 13C recovery in flooded leaves increased compared to controls, whereas roots exhibited the opposite pattern. Interestingly, when carbohydrate partitioning was examined, the data revealed that sucrose concentration was augmented significantly in roots (37-56%), whereas starch was reduced. In leaves, a marked increase in sucrose was detected from the first sampling onwards (36-66%), and the same patter was observed for starch. Taken together, these results indicate that flooding altered carbon and nitrogen pools and partitioning in citrus. On one hand, reduced nitrogen concentration appears to be a consequence of impaired uptake and transport. On the other hand, the observed changes in carbohydrate distribution suggest that translocation from leaves to roots was reduced, leading to significant starch accumulation in leaves and further decreases in roots. PMID- 22673031 TI - Geraniol synthase whose mRNA is induced by host-selective ACT-toxin in the ACT toxin-insensitive rough lemon (Citrus jambhiri). AB - Host-selective toxins (HSTs) produced by some strains of Alternaria alternata are selectively toxic to certain cultivars of plants. However, the role of HSTs in toxin-insensitive plants is currently unknown. Here, we studied the role of ACT toxin using an ACT-toxin producing A. alternata strain SH20 and the ACT-toxin insensitive plant rough lemon. Induction of some defense related genes in response to SH20 were faster or stronger than in response to the ACT-toxin deficient SH20 mutant. By sequencing subtractive PCR clones obtained from mRNA of rough lemon leaves inoculated with SH20 after subtraction with that of the ACT toxin deficient SH20 mutant, we isolated the SH20-responsive genes in rough lemon. Among the SH20-responsive genes analyzed in this study, we isolated a terpene synthase (TPS) gene, RlemTPS3. We also determined that RlemTPS3 localizes to the chloroplast and produces the monoterpene geraniol. PMID- 22673032 TI - Circulating pituitary and gonadal hormones in spring-born Thoroughbred fillies and colts from birth to puberty. AB - The present study was conducted to elucidate the profile of circulating gonadotropins and gonadal hormones from birth to puberty and relationship between gonadal seasonality and hormonal secretion in both sexes of Thoroughbred horses. Spring-born colts (n=6) and fillies (n=9) were blood sampled weekly from jugular vein from birth to 60 weeks of age. Circulating FSH, LH, prolactin, testosterone, progesterone, estradiol-17beta, and immunoreactive (ir)-inhibin were measured by radioimmunoassay. In both sexes, the steroid hormones levels were remarkably high at birth, rapidly dropped within a week and remained at the lower levels until the start of second spring after birth. Ir-inhibin was also high during the birth, remaining lowest during winter and again increasing towards the second summer. There was an increase in FSH concentration in foals during the first summer months after birth and in the next summer, the FSH concentration along with that of LH increased significantly. The seasonal increase in circulating prolactin was remarkable even in the first year, and no differences were noted between the two summers. These results clearly demonstrated that the hypothalamo pituitary axis is already responsive to changes in photoperiod and secrete prolactin similar to adult horses, but pituitary gonadotrophs for FSH and LH secretion is less sensitive. When the values of these hormones in the second breeding season after birth were compared with adult values of the respective sex in the breeding season, no significant differences were observed, indicating that spring-born fillies and colts have already attained the stage of puberty at the second breeding season after birth. PMID- 22673033 TI - Pharmacokinetic evidence on the contribution of intestinal bacterial conversion to beneficial effects of astragaloside IV, a marker compound of astragali radix, in traditional oral use of the herb. AB - Astragaloside IV (AIV) is the most abundant saponin and a marker compound in Astragali Radix, a Chinese herb notable for its anti-aging and immune-enhancing effects. The present study investigated the role of intestinal bacterial conversion in the in vivo fate of AIV administered through a traditional oral route for the first time. When incubated anaerobically with rat intestinal bacteria, AIV generated five metabolites with three [monoglycosides brachyoside B and cyclogaleginoside B, the aglycone cycloastragenol (CA)] via stepwise deglycosylation and two from further epimerization (CA-iso) and dehydrogenation (CA-2H). Hydrolytic removal of C-6 glucose was a rate-limiting step for formations of CA and its derivatives. When AIV was orally administered to the rat, CA and CA-iso presented as the main components in plasma following AIV, and the AUC(0-infinity) were 88.60 +/- 9.66 (CA), 179.06 +/- 28.53 (CA-iso) and 452.28 +/- 43.33 nM.h (AIV). CA-2H was the predominant form in feces but was not detected in urine or plasma. This agreed well with in vitro data including rapid hepatic metabolism of CA-2H to form CA and CA-iso and reversible conversions between CA-2H and CA/CA-iso by intestinal bacteria. These findings support a crucial role of gut bacterial conversion of AIV in the traditional application of Astragali herb and warrant further investigational emphasis on CA and CA-iso. PMID- 22673034 TI - Evaluation of human embryonic stem cell-derived hepatocyte-like cells for detection of CYP1A inducers. AB - There is a great deal of interest in differentiation of human embryonic stem cells (hESCs) into hepatocyte-like cells for application in pharmaceutical screening. Cytochrome P450 (CYP) 1A is involved in the metabolic activation of procarcinogenic compounds as well as in detoxification of drugs. We differentiated hESCs into hepatocyte-like cells (hESC-derived hepatocyte-like cells) and examined whether CYP1A was induced in these cells by typical inducers of CYP1A. hESC-derived hepatocyte-like cells expressed albumin, alpha fetoprotein, CYP3A4, CYP3A7, CYP1A1, CYP1A2, and UDP-glucuronyl transferase (UGT) 1A1 mRNA. The levels of CYP1A1, CYP1A2, and UGT1A1 mRNA expression were increased by omeprazole and 3-methylcholanthrene. Furthermore, the enzyme activity of CYP1A was also increased by these compounds. In conclusion, hESC-derived hepatocyte like cells are available for the detection of CYP1A inducers. PMID- 22673035 TI - Does robotic gait training improve balance in Parkinson's disease? A randomized controlled trial. AB - BACKGROUND: Treadmill training (with or without robotic assistance) has been reported to improve balance skills in patients with Parkinson's disease (PD). However, its effectiveness on postural instability has been evaluated mainly in patients with mild to moderate PD (Hoehn & Yahr stage <=3). Patients with more severe disease may benefit from robot-assisted gait training performed by the Gait-Trainer GT1, as a harness supports them with their feet placed on motor driven footplates. The aim of this study was to determine whether robot-assisted gait training could have a positive influence on postural stability in patients with PD at Hoehn & Yahr stage 3-4. METHODS: Thirty-four patients with PD at Hoehn & Yahr stage 3-4 were randomly assigned into two groups. All patients received twelve, 40-min treatment sessions, three days/week, for four consecutive weeks. The Robotic Training group (n = 17) underwent robot-assisted gait training, while the Physical Therapy group (n = 17) underwent a training program not specifically aimed at improving postural stability. Patients were evaluated before, immediately after and 1-month post-treatment. Primary outcomes were: Berg Balance scale; Nutt's rating. RESULTS: A significant improvement was found after treatment on the Berg Balance Scale and the Nutt's rating in favor of the Robotic Training group (Berg: 43.44 +/- 2.73; Nutt: 1.38 +/- 0.50) compared to the Physical Therapy group (Berg: 37.27 +/- 5.68; Nutt: 2.07 +/- 0.59). All improvements were maintained at the 1-month follow-up evaluation. CONCLUSIONS: Robot-assisted gait training may improve postural instability in patients with PD at Hoehn & Yahr stage 3-4. PMID- 22673036 TI - VPS35 gene variants are not associated with Parkinson's disease in the mainland Chinese population. AB - VPS35 gene mutation has recently been reported in autosomal-dominant, late-onset Parkinson disease (PD). There are no reports regarding the association between VPS35 and Parkinson's disease (PD) in the Chinese population. We conducted a comprehensive genetic analysis of VPS35 gene in a cohort of twenty seven probands belonging to families with autosomal-dominant, late-onset PD, followed up with screening of specific variants in a separate group of 1011 sporadic PD patients and 1016 healthy controls. Our analysis revealed two exonic variants and three intronic variants across the entire VPS35 gene. There was no statistical difference in genotype or allele frequencies of rs3743928 and IVS14-24 t > c variants in VPS35 gene between sporadic PD group and healthy control group. None of the 1011 sporadic PD patients and 1016 controls carried the VPS35 gene c.1858G > A (p.Asp620Asn) mutation. Our data indicated that the VPS35 variants are not associated with PD in the mainland Chinese population. PMID- 22673037 TI - The age-dependency of genetic and environmental influences on serum cytokine levels: a twin study. AB - Previous epidemiologic studies have evaluated the use of immunological markers as possible tools for measuring ageing and predicting age-related pathology. The importance of both genetic and environmental influences in regulation of these markers has been emphasized. In order to further evaluate this relationship, the present study aims to investigate the relative influence of genetic and environmental factors on four key cytokines involved in the human immune response (Interleukin (IL)-1beta, IL-6, IL-10 and Tumor Necrosis Factor (TNF)-alpha). In addition, the role of age as a possible moderator on these influences was evaluated. METHODS: The study was conducted in 1603 females from the Twins UK registry, with mean age +/- SD of 60.4 +/- 12.2 years, including 863 monozygotic twins (385 pairs and 93 singletons) and 740 dizygotic twins (321 pairs and 98 singletons). Heritability was estimated using structural equation modeling. The role of age as a moderator was evaluated using gene-age interaction models. RESULTS: Heritabilities were moderate for IL-1beta (range: 0.27-0.32) and IL-10 (0.30) and low for IL-6 (range: 0.15-0.16) and TNF-alpha (range: 0.17-0.23). For IL-1beta, heritability declines with age due to an increase in unique environmental factors. For TNF-alpha, heritability increases with age due to a decrease in unique environmental factors. CONCLUSION: The current findings illustrate the importance of genetic and environmental influences on four cytokines involved in the human immune response. For two of these there is evidence that heritability changes with age owing to changes in environmental factors unique to the individual. PMID- 22673039 TI - Adolescent pregnancy and the risk of Plasmodium falciparum malaria and anaemia-a pilot study from Sekondi-Takoradi metropolis, Ghana. AB - The problem of malaria in adolescence has been surpassed by the immense burden of malaria in children, most especially less than 5. A substantial amount of work done on malaria in pregnancy in endemic regions has not properly considered the adolescence. The present study therefore aimed at evaluating the prevalence of Plasmodium falciparum and anaemia infection in adolescent pregnant girls in the Sekondi-Takoradi metropolis, Ghana. The study was carried out at four hospitals in the Sekondi-Takoradi metropolis of the western region of Ghana from January 2010 to October 2010. Structured questionnaires were administered to the consenting pregnant women during their antenatal care visits. Information on education, age, gravidae, occupation and socio-demographic characteristics were recorded. Venous bloods were screened for malaria using RAPID response antibody kit and Geimsa staining while haemoglobin estimations were done by cyanmethemoglobin method. The results revealed that adolescent pregnant girls were more likely to have malaria infection than the adult pregnant women (34.6% verses 21.3%, adjusted OR 1.65, 95% CI, 1.03-2.65, P=0.039). In addition, adolescent pregnant girls had higher odds of anaemia than their adult pregnant women equivalent (43.9% versus 33.2%; adjusted OR 1.63, 95% CI, 1.01-2.62, P=0.046). Taken together, these data suggest that adolescent pregnant girls were more likely to have malaria and anaemia compared to their adult pregnant counterpart. Results from this study shows that proactive adolescent friendly policies and control programmes for malaria and anaemia are needed in this region in order to protect this vulnerable group of pregnant women. PMID- 22673038 TI - Influence of depressed mood and psychological stress symptoms on perceived oral contraceptive side effects and discontinuation in young minority women. AB - BACKGROUND: We examined the influence of depressed mood and psychological stress on oral contraceptive (OC) side effects and discontinuation. STUDY DESIGN: We administered standard psychological instruments to 354 young women (13-24 years old) beginning a 6-month OC continuation intervention trial and questions on OC side effects and use at 6 months. Logisitic regression determined the relationships between psychological conditions, perceived OC side effects and continuation rates. RESULTS: Baseline depressed mood (21%) and stress (19%) and 6 month mood (25%) and weight changes (57%) were relatively common. Only 38% continued OCs at 6 months. Depressed mood [odds ratio (OR) 2.27, confidence interval (CI) 1.25-4.15, p=.007] and stress (OR 2.07, CI 1.12-3.82, p=.02) were associated with perceived OC-related moodiness; depressed mood was associated with perceived weight loss (OR 1.89, CI 1.01-3.55, p=.05). Depressed mood (OR 0.54, CI 0.29-0.99, p=.04), stress (OR 0.48, CI 0.25-0.91, p=.03) and perceived weight change (OR 0.60, CI 0.38-0.94, p=.03) all reduced the likelihood of OC continuation. CONCLUSION: Young women with adverse psychological symptoms are at risk for perceived OC side effects and discontinuation. PMID- 22673040 TI - Primary non-Hodgkin's lymphoma of the skull base: a case report and literature review. PMID- 22673041 TI - O-Arm-based image guidance in minimally invasive spine surgery: technical note. AB - Three-dimensional (3D) image guidance technology is gaining popularity in spine surgery. The O-Arm navigation platform, which relies on cone-beam CT images acquired in the operative position, represents the most recent advancement in this field. We report our technique for MIS pedicle screw insertion using the O Arm system and present two illustrative cases. We used percutaneous technique for short construct cases and "transfascial" technique for long-construct cases. O Arm based navigation in minimally invasive spine surgery is safe and feasible. This technology may improve surgical accuracy and clinical outcomes but long term prospective studies are needed to validate this. PMID- 22673042 TI - How active are patients with idiopathic normal pressure hydrocephalus and does activity improve after shunt surgery? A controlled actigraphic study. AB - INTRODUCTION: Actigraphy allows long-time evaluation of physical activity and resting behaviour in a normal environment. The aim of this study was, by use of actigraphy, to measure motor function, energy expenditure and resting/sleeping time in idiopathic normal pressure hydrocephalus (iNPH) patients before and after surgery, and compare the results with healthy individuals (HI). SUBJECTS AND METHODS: 33 patients (mean 73 year) and 17 HI (mean 73 year) participated. Actigraphy with SenseWear (BodyMedia Inc., Pittsburgh, PA, USA) was recorded in the iNPH patients before and three months postoperatively and twice in the HI with a three-month interval. In addition, gait speed, timed up and Go (TUG) and MMSE were registered pre- and post-operatively. RESULTS: During daytime the patients took fewer steps (p < 0.001) and their total energy expenditure (TEE) was lower (p < 0.01) than in the HI. Twenty patients were evaluated pre- and post operatively and no change in either the number of steps, TEE, or time spent lying/sleeping after surgery could be detected. iNPH patients had lower gait speed, worse TUG and MMSE compared to the HI. Gait and TUG improved after surgery. CONCLUSION: Actigraphy in iNPH patients indicated reduced ambulatory activity and lower energy expenditure compared to HI preoperatively. This did not change postoperatively in spite of improved TUG and gait speed. PMID- 22673043 TI - Impact of genetic variation in breast cancer resistance protein (BCRP/ABCG2) on sunitinib pharmacokinetics. AB - To elucidate the impact of genetic variations in breast cancer resistance protein (BCRP/ABCG2) and P-glycoprotein (MDR1/ABCB1) on the pharmacokinetics of sunitinib, we carried out a pharmacogenetic study in a clinical setting and pharmacokinetic analysis using Abcg2(-/-), Abcb1a/1b(-/-) and Abcb1a/1b;Abcg2(-/ ) mice. Nineteen renal cell carcinoma patients were enrolled in this study. The plasma concentrations of sunitinib and its active metabolite were determined and the area under the concentration-time curve (AUC) was calculated. Genetic polymorphisms in ABCG2 (421C>A) and ABCB1 (1236C>T, 2677G>T/A and 3435C>T) were examined. The dose-adjusted AUC(0-24) of sunitinib was significantly higher in patients with a heterozygous variant for ABCG2 421C>A than in wild-type patients (p = 0.02), and one homozygous patient showed the highest dose-adjusted AUC(0 24). The ABCB1 polymorphisms were not associated with the dose-adjusted AUC(0 24). The maximum concentration and AUC(0-4) of sunitinib were significantly higher in Abcg2(-/-), Abcb1a/1b(-/-) and Abcb1a/1b;Abcg2(-/-) mice than wild-type mice when sunitinib was given orally but not intraperitoneally. Incidence of thrombocytopenia and hypertension and poor compliance were associated with the systemic exposure to sunitinib and its active metabolite. These results suggest that the loss of protein expression of ABCG2 by genetic polymorphism is associated with an increase in the systemic exposure to sunitinib and sunitinib induced toxicity. PMID- 22673044 TI - Pathoanatomy and classification of low back disorders. AB - Over the past decade research into the effectiveness of low back disorders (LBDs) has focused on the classification of subgroups more likely to respond to specific treatment. Much of this research has explicitly excluded a focus on pathoanatomical factors based on a questionable interpretation of the biopsychosocial model. Common justifications and potential issues with this approach are explored with recommendations made for future clinical and research practice. PMID- 22673045 TI - The quality of cryopreserved sperm collected from feline caudal epididymides using seminal plasma. AB - It is thought that differences in conception rate between feline epididymal sperm and ejaculate sperm occur because, unlike ejaculated sperm, caudal epididymal sperm have not been sensitized with seminal plasma (SP). In this study, we investigated whether collection of feline epididymal sperm with SP influences sperm qualities after freezing-thawing. Sperm were sensitized with SP for 10 min at room temperature. As a result, the motility of caudal epididymal sperm sensitized with SP immediately after collection was significantly lower than that of ejaculate sperm, and no difference was noted in sperm qualities after freezing thawing. This shows that the qualities of caudal epididymal sperm cannot be improved to a level higher than those of ejaculate sperm by sensitization with SP. PMID- 22673046 TI - Direct synthesis of vertically aligned ZnO nanowires on FTO substrates using a CVD method and the improvement of photovoltaic performance. AB - In this work, we report a direct synthesis of vertically aligned ZnO nanowires on fluorine-doped tin oxide-coated substrates using the chemical vapor deposition (CVD) method. ZnO nanowires with a length of more than 30 MUm were synthesized, and dye-sensitized solar cells (DSSCs) based on the as-grown nanowires were fabricated, which showed improvement of the device performance compared to those fabricated using transferred ZnO nanowires. Dependence of the cell performance on nanowire length and annealing temperature was also examined. This synthesis method provided a straightforward, one-step CVD process to grow relatively long ZnO nanowires and avoided subsequent nanowire transfer process, which simplified DSSC fabrication and improved cell performance. PMID- 22673047 TI - [Management of a case of unilateral exophthalmos due to an intraorbital lipofibroma at Kara teaching hospital in Togo]. AB - In childhood, benign tumors are uncommon causes of exophtalmos. We report a case of intraorbital lipofibroma in an 11-year-old girl who presented with painless, progressive proptosis of the right eye over the preceding 6 months. Ultrasound had shown an extraconal intraorbital mass. Complete excision and pathologic examination were performed, revealing a lipofibroma with no signs of malignancy This case report is notable due to the rarity of the condition. PMID- 22673048 TI - [Spontaneous resorption of a sub-internal limiting membrane macular hemorrhage in Terson's syndrome]. PMID- 22673049 TI - [Relationships between refractive parameters: sphere, cylinder and axis]. AB - PURPOSE: To analyze the relationships between refractive parameters as well as the relationship between fellow eyes in a normal population. METHODS: Both subjective refraction and auto-refractometry data of 500 patients were prospectively recorded. Refraction data were analyzed on three rectangular coordinates in a dioptric space. WTR/ATR ratio of axis was quantified by the Cos2axis function. Enantiomorphism (mirror-image symmetry) between fellow eye axes was quantified by the absolute value of the difference between 180 degrees and the sum of both axes. RESULTS: Mean refraction and mean cylinder were -1.74D (+0.28D * 91.5 degrees ) and 0.81 +/- 0.89D respectively. The spherical component had no significant influence on refractive astigmatism (r(s)<= 0.07, P >= 0.07) except for high spherical ametropia. Eyes with spherical equivalent greater than 4D (in absolute value) demonstrated higher cylinder (1.15D vs 0.84D, P<0.001). Cylinder influenced the WTR/ATR ratio (r(s)=-0.25, P<0.001) and the enantiomorphism (r(s)=0.36, P<0.001). Age also influenced the WTR/ATR ratio (r(s)=0.27, P<0.001) and the enantiomorphism (r(s)=0.14, P<0.001). Axes were more likely WTR and enantiomorphic when the cylinder was high and the subject young. Oblique axes were less enantiomorphic (35.5 degrees vs 20.6 degrees , P<0.001) and were associated with lower cylinder (0.56D vs 0.98D, P<0.001). Correlation between fellow eyes was significant for cylinder (r(s)=0.66, P<0.001) and for spherical equivalent (r(s)=0.96, P<0.001). Gender had no significant influence on refraction (P>0.12) except for spherical equivalent (relative hyperopia of +0.17D, P=0.04 in females). CONCLUSION: The spherical component of the refraction appears to be independent of the refractive astigmatism except for high spherical ametropia. Cylinder influences somewhat the WTR/ATR ratio of axis and the enantiomorphism. Relationships between refractive parameters are weak in comparison to the fellow eye relationships. PMID- 22673050 TI - N3,N7-diaminophenothiazinium derivatives as antagonists of alpha7-nicotinic acetylcholine receptors expressed in Xenopus oocytes. AB - Derivatization of phenothiazine (PTZ, 1) has been a commonly used method to develop drugs with various pharmacological properties. In the present study, a series of PTZ derivatives 1-11 were investigated on the inhibition of the cloned alpha7 subunit of the human nicotinic acetylcholine receptor (alpha7-nAChR) expressed in Xenopus oocytes by using the two-electrode voltage-clamp technique. In the first series of experiments, the effect of unsubstituted phenothiazine 1 on alpha7-nAChRs was compared with that of the N3,N7-diaminophenothiazin-5-ium derivative 2, and of sequentially methylated derivatives 3-6. In the second set of experiments, the effects of N3,N7-tetra-ethyl- to n-hexylphenothiazin-5-ium derivatives 7-11 were tested. Despite the lack of activity found for 1, a reversible inhibition of alpha7-nAChRs, ranging from moderate to potent, was observed as a result of a sequential amine- and methylamine substitution of 1. The inhibition of ACh (100 MUM)-induced currents was concentration-dependent with IC(50) values ranging from 0.4 to 16.8 MUM. However, an optimal inhibitory activity was achieved by prolongation of alkyl chains up to propyl size, as found in PTZ derivative 8, whereas further lengthening of alkyl chains to n-butyl-, n pentyl-, or n-hexyl groups resulted in inactive derivatives 9-11. The results evidently suggest the presence of a lipophilic binding pocket of narrow tolerability on the receptor protein. These results emphasize the importance of amine and/or alkylamine moieties for the inhibitory effect of PTZ derivatives and provide further insights for the development of novel antagonists targeting alpha7-nAChRs. PMID- 22673051 TI - Osteochondritis dissecans of the talar head: natural history and review of literature. AB - Osteochondritis dissecans (OCD) of the talar dome is relatively common, however, OCD of the talar head is extremely rare. We present two cases of OCDs of the talar head. This report describes the natural history of this rare condition and its evolution until skeletal maturity. The literature of OCD in this unusual location is reviewed. PMID- 22673053 TI - Quieting the overactive hippocampus restores memory in aging. AB - A recent study by Bakker et al. shows that a low dose of the antiepileptic drug levetiracetam reduces hippocampal hyperactivity in elderly humans with amnestic mild cognitive impairment and improves hippocampal memory function. This points towards a new treatment strategy for age-related memory impairment by reducing deleterious overactivity of the hippocampus. PMID- 22673052 TI - Hippocampal sequences link past, present, and future. AB - Disrupting the reactivation of hippocampal neurons during sleep impairs memory consolidation in rats. However, the functional importance of reactivation during awake states is unknown. An experiment in which awake reactivation was disrupted suggests that this phenomenon could adaptively guide behavior by linking previous learning with the current state of the world. PMID- 22673054 TI - Key role of glycogen storage in high K+-induced contraction of the smooth muscles of the bovine trachea. AB - To elucidate the role of glycogen in the contraction of tracheal smooth muscle, we investigated the changes in the glycogen contents of the bovine trachea during contractions induced by high K(+) and hypoxia (achieved by bubbling N(2) instead of O(2)), either in a glucose-free condition or in the presence of iodoacetic acid (IAA), an inhibitor of glycolysis. Hyperosmotic addition of 65 mM KCl (H-65 K(+)) induced a sustained contraction. A glucose-free condition did not affect H 65 K(+)-induced contraction. However, hypoxia slightly inhibited the contraction, and glucose-free PSS with hypoxia or IAA remarkably inhibited the H-65 K(+) induced contraction. H-65 K(+) induced a sustained increase in reduced pyridine nucleotide (PNred) fluorescence, representing glycolysis activity. Hypoxia alone slightly enhanced PNred fluorescence, and when combined with a glucose-free condition, it remarkably enhanced the H-65 K(+)-induced PNred fluorescence. IAA inhibited PNred fluorescence. In the presence of H-65 K(+), a glucose-free condition, hypoxia and the combination of glucose-free PSS and hypoxia decreased the glycogen contents. However, IAA had no effect on glycogen contents. Although hypoxia or glucose-free PSS did not affect PCr and ATP contents, the combination of hypoxia and glucose-free PSS or IAA induced a gradual decrease of PCr content. In conclusion, we suggest that endogenous glycogen was utilized to increase the activity of glycolysis for maintaining high K(+)-induced contraction of the bovine trachea in the glucose -free and/or hypoxic condition. PMID- 22673055 TI - Heavy metal removal in phytofiltration and phycoremediation: the need to differentiate between bioadsorption and bioaccumulation. AB - Phytoremediation and phycoremediation are cost-effective and environmentally sound technologies for the treatment of polluted streams and wastewaters contaminated with metals. Currently, the most commonly used parameter to assess the metal uptake of biomass is (q) expressed as mg metal g dry weight(-1). By contrast, the bioconcentration factor (BCF) is one of the most widely used factors to evaluate the metal uptake capacity of macrophytes. However, both parameters the metal uptake (q) and the BCF cannot be applied to differentiate between the ability of live plants or photosynthetic microorganisms to adsorb the metal onto their surface through passive mechanisms or to accumulate the contaminant at intracellular level through metabolically active mechanisms. This mini review has the objective of discussing the need to differentiate between bioadsorption and bioaccumulation of metals in live plants and photosynthetic microorganisms used in phytofiltration and phycoremediation processes, respectively. The use of two specific factors, the bioadsorption factor (BAF) and the intracellular accumulation factor (IAF) that have been previously reported in order to make a clear differentiation between these two metal removal mechanisms in Salvinia minima and Leptolyngbya crossbyana is highlighted. It is suggested that the BAF and the IAF can be used in phytofiltration wetlands and phycoremediation lagoons, where there is the need of specific information indicating the fate of the metal in order to gain information about possible removal mechanisms. These factors could also provide a tool to decide whether it is possible to harvest the biomass and to recover a fair amount of metal adsorbed onto the surface by means of desorbent agents. A critical assessment of the use of EDTA as desorbent agent is also included. PMID- 22673056 TI - Pathological vascular invasion and tumor differentiation predict cancer recurrence in stage IA non-small-cell lung cancer after complete surgical resection. AB - INTRODUCTION: The appropriate therapeutic strategy and postoperative management for patients with stage IA non-small-cell lung cancer (NSCLC) still remain a matter of debate because of the prognostic heterogeneity of this population, including the risk of cancer recurrence. The objective of the current study was to identify the clinicopathological factors that affect overall prognosis and cancer recurrence of stage IA NSCLC. METHODS: We reviewed the data of 532 patients in whom complete resection of stage IA NSCLC had been performed. Overall survival and recurrence-free proportion (RFP) were estimated using the Kaplan Meier method. RFP was estimated from the date of the primary tumor resection to the date of the first recurrence or last follow-up. We performed univariate and multivariate analyses to determine the independent prognostic factors. RESULTS: On multivariate analyses, three variables were shown to be independently significant recurrence risk factors: histological differentiation (hazard ratio [HR] = 1.925), blood-vessel invasion (HR = 1.712), and lymph-vessel invasion (HR = 1.751). On subgroup analyses combining these risk factors, the 5-year RFP was 91.3% for patients with no risk factors, 79.5% for those with either poorly differentiated carcinoma or vascular invasion, (p < 0.001 for both), and 62.9% for those with both poorly differentiated carcinoma and vascular invasion (p = 0.068). CONCLUSION: These results indicated that vascular invasion and tumor differentiation have a significant impact on the prediction of cancer recurrence in patients with stage IA NSCLC. Patients with these predictive factors of recurrence may be good candidates for adjuvant chemotherapy. PMID- 22673057 TI - Do arbuscular mycorrhizal fungi affect arsenic accumulation and speciation in rice with different radial oxygen loss? AB - The effects of arbuscular mycorrhizal fungi (AMF) on the temporal variation of arsenic (As) speciation and accumulation in two paddy rice cultivars (TD 71 and Xiushui 11) with different degrees of radial oxygen loss (ROL) at three growth periods (day 7, day 35, day 63 after flooding the soil) were investigated in soil, spiked with and without 30 mg As kg(-1). The results showed that TD 71 with high ROL colonized by Glomus intraradices led to higher root colonization rates than Xiushui 11 at three growth periods, both in soil with or without 30 mg As kg(-1) (p<0.05). Mycorrhizal inoculation led to elevated (p<0.05) root ratios of arsenite (As(III)) conc./arsenate (As(V)) conc. (concentration) in TD 71 with high ROL at three growth periods in As contaminated flooding soils. Furthermore, the ratios of As(III) conc./As(V) conc. in roots of TD71 were significantly more than Xiushui 11 when colonized by AMF at three growth periods in 30 mg As kg(-1) soil (p<0.05). Therefore, rice with high ROL can favor AM fungal infection and enhance root ratio of As(III) conc./As(V) conc. in the presence of AMF. PMID- 22673058 TI - Ammonium pyrrolidine dithiocarbamate anchored Symphoricarpus albus biomass for lead(II) removal: batch and column biosorption study. AB - The biosorption properties of APDC modified S. albus were tested in batch and column conditions. Effective experimental parameters such as pH, biosorbent dosage, contact time, temperature, initial lead(II) ion concentration, flow rate and bed height were investigated. The biosorption capacity of modified biosorbent was at maximum when lead(II) solution pH and biosorbent dosage were 5.5 and 2.0 g L(-1), respectively. The biosorption equilibrium was established in 20 min. Langmuir isotherm fitted well to the equilibrium data and kinetics is found to fit pseudo-second-order model. Increase in ionic strength of lead(II) solutions caused a slight decrease in the biosorption yield of APDC-modified biosorbent. Co ions affected the biosorption performance of modified biomass up to maximum 20.81% reduction. Column biosorption of lead(II) showed higher biosorption yields at lower flow rates. Required time of breakthrough point was found to be 200 min. The recommended mechanism was found to depend mainly on electrostatic interaction, ion-exchange and complex formation. The ion-exchange mechanism for lead(II) biosorption onto the modified biosorbent is verified from the ionic strength effect and EDX analysis. Carbonyl, phosphate and CN groups on the modified surface of S. albus were found to responsible for complexation with lead(II). PMID- 22673059 TI - Synthesis and characterization of SiC and SiC/Si3N4 composite nano powders from waste material. AB - In the present work, nano silicon carbide has been prepared by pyrolysis of rice husk ashes as starting materials. Three rice-husk ash samples having different features were used. The first was coarse-grained rice husk ash (fired husk as is), the second was fine rice husk ash (hand-ground), while the third was ball milled one. Effect of ball milling of the starting ashes for 6h on the formation of nano SiC was investigated and compared with those prepared without milling. The particle sizes of the prepared SiC materials were affected by the milling process. The particle sizes of the obtained nano SiC from ball milled staring materials were smaller than those prepared without milling. The pyrolysis conditions, i.e. the temperature and atmosphere were optimized. The optimum firing temperature to obtain well crystalline nano SiC was 1550 degrees C. The effect of pyrolysis atmosphere, i.e. argon, vacuum and nitrogen was also demonstrated. The pyrolysis in argon exhibited lower efficiency on the formation of SiC than vacuum; while the pyrolysis in nitrogen atmosphere led to formation of SiC/Si(3)N(4) nanocomposite. PMID- 22673060 TI - Exploring element accumulation patterns of a metal excluder plant naturally colonizing a highly contaminated soil. AB - This work investigates the element distribution in Silene paradoxa growing on the mine dump of Fenice Capanne (Tuscany, Italy). The accumulation of As, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb and Zn in root apoplast and symplast and in shoot was assessed and compared to the levels of the same metals in the respective rizosphere soils, analyzing both the total and the phytoavailable fractions. Levels of As, Cu, Fe, Pb and Zn, were above toxicity thresholds in both soil and shoot samples. Inter- and intra-element correlations were analyzed in plant and soil using different statistical methods. Soil total and phytoavailable metal concentration were shown not to be dominant in determining metal accumulation by the plant, since no significant positive correlation was found between metal concentration in soils and plants. Moreover, results indicated that S. paradoxa was able to cope with the studied multi-metal contaminated soil excluding the elements from its tissues and preferentially accumulating them into the root compartment, thus suggesting this species as possible good candidate for phytostabilization purposes. PMID- 22673061 TI - Pareto frontier analyses based decision making tool for transportation of hazardous waste. AB - Transportation of hazardous wastes through a region poses immense threat on the development along its road network. The risk to the population, exposed to such activities, has been documented in the past. However, a comprehensive framework for routing hazardous wastes has often been overlooked. A regional Hazardous Waste Management scheme should incorporate a comprehensive framework for hazardous waste transportation. This framework would incorporate the various stakeholders involved in decision making. Hence, a multi-objective approach is required to safeguard the interest of all the concerned stakeholders. The objective of this study is to design a methodology for routing of hazardous wastes between the generating units and the disposal facilities through a capacity constrained network. The proposed methodology uses posteriori method with multi-objective approach to find non-dominated solutions for the system consisting of multiple origins and destinations. A case study of transportation of hazardous wastes in Kolkata Metropolitan Area has also been provided to elucidate the methodology. PMID- 22673062 TI - Efficacy and safety of firocoxib for the treatment of pain associated with soft tissue surgery in dogs under field conditions in Japan. AB - Use of firocoxib in dogs for postoperative pain control has not been published in any of the journals in Japan. A field study was conducted to evaluate the efficacy and safety of firocoxib in dogs in controlling pain associated with soft tissue surgery in Japan. The study followed a negative control, double-blind, multicenter clinical efficacy study using a randomized block design. A total of 131 client-owned dogs presented to the clinical practices for soft tissue surgery were enrolled. Sixty-nine dogs were allocated to the firocoxib-treated group and received 5 mg/kg of firocoxib orally on Day 0 before the surgery and once daily through Day 2, while 62 dogs were allocated to the non-treated group handled in a similar manner only without the firocoxib administration. Pain assessment took place on Day 0 before the surgery through Day 2. The primary efficacy variable was a success/failure variable based on whether the dog needed rescue medication (based on pain assessment after the surgery or Investigator's judgment) and a significant difference between firocoxib-treated group (16.4%) and non-treated group (50.0%) (P=0.0031) was observed. There was no adverse event during the study that was considered to be related to the administration of firocoxib. This study indicated the clinical efficacy and safety profile of firocoxib administered to control pain associated with soft tissue surgery under field condition. PMID- 22673063 TI - In vivo electroporation induces cell cycle reentry of myonuclei in rat skeletal muscle. AB - Adult urodele amphibians such as newts are capable of regenerating lost structures including their limbs. In these species, dedifferentiation of myofiber is essential for the regenerative process. Upon terminal differentiation, nuclei of myofiber (myonuclei) are withdrawn from cell cycle, but prior to dedifferentiation, myonuclei reenter the cell cycle. In contrast with urodele amphibians, it is generally accepted that mammalian myofibers are not able to dedifferentiate in response to muscle injury. A recent study has suggested that electroporation can induce dedifferentiation response of skeletal muscle in newt limbs. In the present study, we examined whether myonuclei of skeletal muscle of mammals are capable of reentering the cell cycle by means of electroporation. Electroporation was applied to tibialis anterior muscle of the rat with or without plasmid DNA. Histological analyses revealed that, while electroporation induces degenerative/regenerative responses in skeletal muscle irrespective of the presence of plasmid DNA, the expression of proliferating cell nuclear antigen (PCNA) in myonuclei was observed only in the presence of plasmid DNA. The present results indicate that myonuclei of skeletal muscle are capable of reentering the cell cycle and suggest that in vivo electroporation can induce dedifferentiation of mammalian skeletal muscle. PMID- 22673064 TI - Directed evolution: an evolving and enabling synthetic biology tool. AB - Synthetic biology, with its goal of designing biological entities for wide ranging purposes, remains a field of intensive research interest. However, the vast complexity of biological systems has heretofore rendered rational design prohibitively difficult. As a result, directed evolution remains a valuable tool for synthetic biology, enabling the identification of desired functionalities from large libraries of variants. This review highlights the most recent advances in the use of directed evolution in synthetic biology, focusing on new techniques and applications at the pathway and genome scale. PMID- 22673066 TI - Chip-based separation devices coupled to mass spectrometry. AB - The hyphenation of miniaturized separation techniques like chip electrophoresis or chip chromatography to mass spectrometry (MS) is a highly active research area in modern separation science. Such methods are particularly attractive for comprehensive analysis of complex biological samples. They can handle extremely low sample amounts, with low solvent consumption. Furthermore they provide unsurpassed analysis speed together with the prospect of integrating several functional elements on a single multifunctional platform. In this article we review the latest developments in this emerging field of technology and summarize recent trends to face current and future challenges in chip-based biochemical analysis. PMID- 22673065 TI - Miniaturized bioanalytical systems: enhanced performance through liposomes. AB - Biorecognition-element labeled liposomes are simple and versatile tools used to amplify signals for the detection of analytes of environmental, clinical, food safety, and national security interest. Relying on measurement of encapsulated species via electrochemical or spectroscopic techniques, or properties inherent to liposomes themselves (such as mass, refractive index, or charge), many advances have been made in both bench-scale and microfluidic applications. Some of these measurement techniques are inherently sensitivity limited, but through the inclusion of liposomes, reduced limits of detection potentially broaden the utility towards otherwise challenging levels of analytes. Other advances took advantage of the hydrophobic environment required by many biorecognition elements to expand the target selectivity range or utilized the amphipathic nature of the lipid bilayer to provide enhanced separation capabilities. Novel handling approaches included wavelength-specific release of contents encapsulated within thermosensitive liposomes or application of electric fields to move, concentrate, and strategically lyse liposomes. These and other topics are discussed in terms of either present incorporation or adaptation to microfluidic devices. PMID- 22673067 TI - How lingering representations of abandoned context words affect speech production. AB - Four experiments tested whether and how initially planned but then abandoned speech can influence the production of a subsequent resumption. Participants named initial pictures, which were sometimes suddenly replaced by target pictures that were related in meaning or word form or were unrelated. They then had to stop and resume with the name of the target picture. Target picture naming latencies were measured separately for trials in which the initial speech was skipped, interrupted, or completed. Semantically related initial pictures helped the production of the target word, although the effect dissipated once the utterance of the initial picture name had been completed. In contrast, phonologically related initial pictures hindered the production of the target word, but only for trials in which the name of the initial picture had at least partly been uttered. This semantic facilitation and phonological interference did not depend on the time interval between the initial and target picture, which was either varied between 200 ms and 400 ms (Experiments 1-2) or was kept constant at 300 ms (Experiments 3-4). We discuss the implications of these results for models of speech self-monitoring and for models of problem-free word production. PMID- 22673068 TI - Shared structural and temporal integration resources for music and arithmetic processing. AB - While previous research has investigated the relationship either between language and music processing or between language and arithmetic processing, the present study investigated the relationship between music and arithmetic processing. Rule governed number series, with the final number being a correct or incorrect series ending, were visually presented in synchrony with musical sequences, with the final chord functioning as the expected tonic or the less-expected subdominant chord (i.e., tonal function manipulation). Participants were asked to judge the correctness of the final number as quickly and accurately as possible. The results revealed an interaction between the processing of series ending and the processing of the task-irrelevant chords' tonal function, thus suggesting that music and arithmetic processing share cognitive resources. These findings are discussed in terms of general temporal and structural integration resources for linguistic and non-linguistic rule-governed sequences. PMID- 22673069 TI - As the front door closes, the back door opens. PMID- 22673071 TI - New strategies for massive transfusion in the bleeding trauma patient. AB - Trauma continues to be the leading cause of death among those younger than 40 years. A major cause of death within the first 24 hours is hemorrhage. Many of these patients present with severe coagulopathy and require massive transfusion. Earlier control of coagulopathy has been shown to improve survival. To address coagulopathy sooner, changes in the way we identify and resuscitate the exsanguinating trauma patient have evolved. These changes include early identification of at-risk patients and early, aggressive transfusion of plasma and platelets. This article reviews the key massive transfusion triggers and resuscitation strategy of damage control resuscitation. PMID- 22673072 TI - Electronic documentation of trauma resuscitations at a level 1 pediatric trauma center. AB - Although many hospitals across the country have implemented an electronic medical record (EMR) for inpatient care, very few have successfully implemented an EMR for trauma resuscitations. Although there is evidence that the EMR improves patient safety, increases access to all care providers, increases workflow efficiency, and minimizes time spent on documenting thereby improving nursing care, the fast paced, complex nature of trauma resuscitations makes it difficult to implement such a system for trauma documentation. With the support of multiple disciplines with a variety of clinical knowledge, this article describes the design process that has led us to successful development and implementation of an EMR for documentation of trauma resuscitations. PMID- 22673073 TI - Understanding trauma as a men's health issue: sex differences in traumatic injury presentations at a level 1 trauma center in Australia. AB - Predominantly, males have a higher risk of injury mortality and morbidity than females. However, less is known about gender differences for injury and trauma outcome at a regional level. The aim of this study was to examine the epidemiologic profile and trauma outcomes of males and females at a level 1 trauma center to inform local injury prevention efforts. A retrospective review was conducted of injuries identified from the trauma registry of the New South Wales St George Public Hospital during January 1, 2004, to December 31, 2008. There were 6763 major trauma presentations, and 65.1% of these were of males. Males had a higher proportion of trauma presentations in each age group, except for those younger than 15 years, 45 to 54 years, and older than 65 years. Almost all presentations were as a result of unintentional injuries. However, 8% of males were victims of assault compared with 2% of females. Males were more likely to be injured while working and during leisure or sports activities and at sporting, farming, home, trade, and industrial locations than females. Males were more likely to be more severely injured than females and generally had a longer hospital length of stay. There was no significant difference in the rate of mortality between the genders. There are distinct differences between the sexes regarding the mechanism and severity of injury and trauma outcomes. Local injury prevention initiatives should be targeted to address gender differences. Future social research should examine the interplay of the construction of masculinities with male injury. PMID- 22673074 TI - Patients with rib fractures: use of incentive spirometry volumes to guide care. AB - Rib fractures pose significant risk to trauma patients. Effective pain control and the ability to take deep breaths are crucial for optimal recovery, and these are key elements in current clinical guidelines. These guidelines use incentive spirometry volumes along with other assessment values to guide patient care. However, despite current guidelines, nurses do not routinely document inspired respiratory volumes. This article provides trauma nurses with the rationale for documenting and tracking incentive spirometry volumes to improve outcomes for patients with rib fractures. This promotes early detection of respiratory decline and early interventions to improve pain control and pulmonary function. PMID- 22673076 TI - Implementation and early outcomes of a peer-led traffic safety initiative for high school students. AB - Compared with other age groups, teenagers have the lowest rate of safety belt use. We sought to determine whether an ongoing, student-led initiative would be effective in increasing safety belt use among high school students compared with another school in which the intervention did not take place. At the intervention school, there was a statistically significant increase of 15% in observed safety belt use and evidence of increased knowledge regarding proper safety belt use. High schools can be effective in changing the traffic safety behaviors of its students. PMID- 22673077 TI - Traumatic distal pancreatic transection: beware of the horses. AB - Blunt pancreatic trauma is rare; however, if missed, it can lead to devastating consequences such as fistula, pancreatitis, and pseudocyst. Blunt trauma accounts for 30% of all pancreatic injuries. High-speed motor vehicle collisions make up the greatest proportion of blunt pancreatic trauma, whereas other causes could be easily overlooked because of being so rare. In this case report we present a case of full-thickness transection of pancreatic tail after being kicked by a horse. The injury was timely identified and successfully treated by completing transection with a stapler. Considering that delay in diagnosis leads to a morbidity rate of 20%, physicians must have high level of suspicion and knowledge of invasive and noninvasive modalities to ensure early detection of pancreatic trauma and a positive outcome. PMID- 22673078 TI - Trauma patient perceptions of nursing care: relationships between ratings of interpersonal care, technical care, and global satisfaction. AB - Interpersonal care is positively associated with patient satisfaction; however, patients may not be able to appreciate their caregivers' technical skills. This cross-sectional telephone survey of trauma patients examined the relationships between patient perceptions of interpersonal care (PIC) and perceived technical care (PTC) and global satisfaction (GS). Structural equation modeling indicated a significant direct effect of PIC on PTC and PTC on GS. Fit indices showed the hypothesized paths significantly improved the model. Strong positive relationships exist between patients' PIC and PTC and GS. Patients unacquainted with technical aspects of health care may make judgments based on satisfaction with perceived interpersonal care. PMID- 22673079 TI - Nursing leaders serving as a foundation for the electronic medical record. AB - Transitioning health care information to an electronic medical record is one of the newest policies to reach the health care agenda. Nursing leaders are at the forefront to affect the design, development, implementation, and reception of an electronic medical record. Because of their clinical workflow knowledge, decision making capacity, and leadership role, nursing leaders are able to achieve high quality EMRs. Being proactive in the reception, design, development, and implementation of an EMR plays a role in creating an organizational culture that allows for the flow of data efficiently and accurately. PMID- 22673081 TI - Utilization of low-molecular-weight heparin prophylaxis in pediatric and adolescent trauma patients. AB - The objective of this study was to use trauma registry data to describe the number and characteristics of patients 21 years or younger receiving thromboprophylaxis with low-molecular-weight heparin at 2 pediatric and 2 adult level 1 trauma centers. Among 706 patients, the average age was 18.5 years, and 94.6% were hospitalized at adult centers. The most common injuries were lower extremity fractures (35.6%) and head injuries (20.4%). Major bleeding was reported in 3 patients (0.4%), and thrombotic events were reported in 15 patients (2.1%). Despite a lack of scientific evidence, low-molecular-weight heparin prophylaxis is being used in young trauma patients (primarily those 14 years or older). Prospective multicenter studies are needed to accurately describe the risks and benefits of low-molecular-weight heparin prophylaxis in young trauma patients, thereby identifying those who truly benefit from this intervention. PMID- 22673082 TI - Nurses as first responders in a mass casualty: are you prepared? AB - A mass casualty event is a situation in which the need for medical care and resources, including personnel, exceeds that which is available. As the largest component of the health care workforce, nurses represent a significant resource that can be called on to act as first responders during a mass casualty. However, current education and national guidelines fail to provide specific instruction on pre-hospital nursing considerations and interventions. This article provides evidence-based guidelines designed for nurses to use when acting as first responders during a disaster and presents recommendations for future nursing practice related to mass casualty events. PMID- 22673083 TI - Structural validation of oral mucosal tissue using optical coherence tomography. AB - BACKGROUND: Optical coherence tomography (OCT) is a non-invasive optical technology using near-infrared light to produce cross-sectional tissue images with lateral resolution. OBJECTIVES: The overall aims of this study was to generate a bank of normative and pathological OCT data of the oral tissues to allow identification of cellular structures of normal and pathological processes with the aim to create a diagnostic algorithm which can be used in the early detection of oral disorders. MATERIAL AND METHODS: Seventy-three patients with 78 suspicious oral lesions were referred for further management to the UCLH Head and Neck Centre, London. The entire cohort had their lesions surgically biopsied (incisional or excisional). The immediate ex vivo phase involved scanning the specimens using optical coherence tomography. The specimens were then processed by a histopathologist. Five tissue structures were evaluated as part of this study, including: keratin cell layer, epithelial layer, basement membrane, lamina propria and other microanatomical structures. Two independent assessors (clinician and pathologist trained to use OCT) assessed the OCT images and were asked to comment on the cellular structures and changes involving the five tissue structures in non-blind fashion. RESULTS: Correct identification of the keratin cell layer and its structural changes was achieved in 87% of the cohort; for the epithelial layer it reached 93.5%, and 94% for the basement membrane. Microanatomical structures identification was 64% for blood vessels, 58% for salivary gland ducts and 89% for rete pegs. The agreement was "good" between the clinician and the pathologist. OCT was able to differential normal from pathological tissue and pathological tissue of different entities in this immediate ex vivo study. Unfortunately, OCT provided inadequate cellular and subcellular information to enable the grading of oral premalignant disorders. CONCLUSION: This study enabled the creation of OCT bank of normal and pathological oral tissues. The pathological changes identified using OCT enabled differentiation between normal and pathological tissues, and identification of different tissue pathologies. Further studies are required to assess the accuracy of OCT in identification of various pathological processes involving the oral tissues. PMID- 22673084 TI - Prevalence of feline coronavirus antibodies in Japanese domestic cats during the past decade. AB - From 2001 to 2010, 17,392 Japanese cats were examined for feline coronavirus (FCoV) antibodies. The seroprevalence of purebreds (66.7%) was higher than that of random breds (31.2%). Seroprevalence increased greatly in purebreds by three months of age, while it did not fluctuate greatly in random breds with aging, indicating that cattery environments can contribute to FCoV epidemics. Purebreds from northern regions of Japan were likely to be seropositive (76.6% in Hokkaido, 80.0% in Tohoku), indicating cattery cats in cold climates might be more closely confined. Among purebreds, the American shorthair, Himalayan, Oriental, Persian, and Siamese showed low seroprevalence, while the American curl, Maine coon, Norwegian forest cat, ragdoll and Scottish fold showed high seroprevalence. There would also be breed-related differences in Japan similar to the previous studies in Australia. PMID- 22673085 TI - Posthodiplostomum sp. Metacercariae in the trunk muscle of northern snakeheads (Channa argus) from the Fushinogawa River, Yamaguchi, Japan. AB - The northern snakehead Channa argus, native to China, Russia and Korea, is currently found widespread throughout Japan following its original introduction during the 1920s. A parasitological study of 10 snakeheads fished from the Fushinogawa River running through Yamaguchi City, Japan, detected 2-101 (average, 23.7) metacercariae per 100 g of trunk muscle from each fish. The trematode was identified as metacercariae of Posthodiplostomum sp. (Strigeidida: Diplostomidae) morphologically and characterized genetically based on the ribosomal RNA gene (rDNA). Phylogenetic trees were constructed on the basis of either the 18S, ITS or 28S region of rDNA to assess the relationship among members of the family Diplostomidae. The addition of genetic data from more diplostomid taxa, particularly Posthodiplostomum cuticola recorded from a variety of freshwater fish in Eurasia, would facilitate the precise identification of the present species. PMID- 22673086 TI - Genotypic change and phylogenetic analysis of porcine circovirus type 2 in Taiwanese pig herds. AB - Porcine circovirus type 2 (PCV2) is the primary causative agent of postweaning multisystemic wasting syndrome. Two major PCV2 genotypes, PCV2a and PCV2b, have been identified. To explore the prevalence of different subgroups of PCV2 in Taiwan, 37 PCV2 isolates collected during 2002-2011 were analyzed. The genotypes of the PCV2 isolates collected before 2007 belonged to either PCV2a or PCV2b. However, all of the isolates collected after 2008 were PCV2b. Most of the isolates obtained since 2008 have been classified into a novel genotype within a subgroup of PCV2b based on complete ORF2 sequence analysis. Moreover, analysis of the PCV2 isolates from the same pig farm but from different years revealed that the viruses shifted from a PCV2b genotype to a novel subgroup of the PCV2b genotype. Collectively, PCV2b was the dominant PCV2 genotype in Taiwan currently, and the viruses have shifted into a new emerging subgroup of the PCV2b genotype. PMID- 22673087 TI - IOP change undergoing anesthesia in rhesus macaques (Macaca mulatta) with laser induced ocular hypertension. AB - The objective of the study was to examine changes of intraocular pressure (IOP) undergoing anesthesia in Rhesus Macaques (Macaca mulatta) with Laser-induced Ocular Hypertension. Twenty male rhesus macaques (hypertensive glaucoma eye in OD; normal eye in OS) between 6 and 20 years of age were used for the study. The monkeys were anesthetized with ketamine hydrochloride (10 mg/kg intramuscularly) and 1% isoflurane, and then IOP in both eyes was measured by a single investigator using a calibrated Tonopen(TM) applanation tonometer (Mentor, Norwell, MA, U.S.A.). The mean IOP with ketamine anesthesia was 36.70 +/- 12.04 (right eye: OD) and 15.88 +/- 2.84 (left eye: OS). The mean IOP with isoflurane anesthesia was 19.98 +/- 6.67 (right eye: OD) and 15.32 +/- 2.15 (left eye: OS). Undergoing isoflurane anesthesia, the IOP of OD was significantly decreased. Conclusively, careful examination of IOP is required to prevent unexpected contraindication on glaucoma patient with isoflurane anesthesia. PMID- 22673088 TI - Cell surface molecules involved in infection mediated by lymphocytic choriomeningitis virus glycoprotein. AB - The glycoprotein (GP) of lymphocytic choriomeningitis virus (LCMV), the prototype arenavirus, is a promising envelope protein of lentiviral pseudotype vectors for gene therapy. The distribution of dystroglycan, a known receptor for LCMV, cannot explain the narrow tropism of LCMV-GP-pseudotypes. Here, we examined whether infection of LCMV-GP-pseudotypes was affected by the expression of four cell surface molecules-Axl and Tyro3 (from the TAM family) and DC-SIGN and LSECtin (from the C-type lectin family)-that are known receptors of Lassa virus, another arenavirus. All four molecules enhanced LCMV-GP-pseudotype infection of cells. These results help explain the tropism of LCMV-GP-pseudotypes and further our understanding of LCMV infection in animals. PMID- 22673089 TI - Breaking the silence: integration of facial disfigurement after surgical treatment for cancer. AB - Little is known about the psychosocial effects of facial disfigurement. We present the results of a qualitative study following 15 patients who had been surgically treated for head, neck, or eye cancer over the course of their first postoperative year. Taped nurse-patient conversations and individual interviews were analyzed using the grounded theory method. The findings revealed that the main concern of the patients was feeling isolated, which was resolved using a process of interactional integration. Interactional integration begins by breaking the silence to enable the progression from a disfigured person to a person with a disfigurement. The model explains the process of adjustment and demonstrates various elements that could be used in interventions targeting patients who experience psychosocial problems. PMID- 22673090 TI - Patient and public involvement in the coproduction of knowledge: reflection on the analysis of qualitative data in a mental health study. AB - Patient and public involvement in health research is increasingly well established internationally, but the impacts of involvement on the research process are hard to evaluate. We describe a process of qualitative data analysis in a mental health research project with a high level of mental health service user and carer involvement, and reflect critically on how we produced our findings. Team members not from research backgrounds sometimes challenged academic conventions, leading to complex findings that would otherwise have been missing. An essential component of how we coproduced knowledge involved retaining methodological flexibility so that nonconventional research voices in the team could situate and critique what was conventionally known. Deliberate and transparent reflection on how "who we are" informed the knowledge we produced was integral to our inquiry. We conclude that reflecting on knowledge (co)production is a useful tool for evaluating the impact of patient and public involvement on health research. PMID- 22673091 TI - General practitioner management of depression: a systematic review. AB - Understanding how primary care clinicians manage depression is a key backdrop to current and future initiatives to improve detection and treatment of depression. We systematically reviewed, identified, and extracted findings from 13 qualitative studies that examined general practitioner (GP) management of depression. We assessed articles for quality using Critical Appraisal Skills Program guidelines for assessing qualitative research but did not exclude any articles based on quality. We carried out a thematic analysis for systematic review of qualitative research in which we identified four main themes with various subthemes: "negotiating the nature of depression," "detect and diagnose," "interventions," and "burden." The results of the analysis illuminate the complex dilemma faced by GPs in managing depression, which appears to be characterized by a sense of dissonance between the medicalization of depression and a sense of its social determinants. PMID- 22673092 TI - When the risks are high: psychological adjustment among melanoma survivors at high risk of developing new primary disease. AB - In this study we explored the psychosocial experiences of melanoma survivors at high risk of developing new primary disease. A total of 20 survivors (9 men, 11 women, mean age 57.6 years) completed a semistructured telephone interview, exploring melanoma-related beliefs and experiences, psychological adjustment to melanoma risk, and supportive care needs. Participants perceived melanoma as potentially terminal and reported persistent worries about the possibility of developing new or metastatic disease. Fear of developing a new melanoma endured for years after treatment completion and, for some, created a pervasive sense of uncertainty. Still, not a single participant sought formal emotional support to address his or her melanoma-related concerns. Belief in the benefits of early intervention, including self- and clinical skin examination, provided a sense of control and a recommended course of action in an otherwise uncontrollable situation. The expertise of the High Risk Clinic physicians was perceived as instrumental in creating a sense of reassurance. PMID- 22673093 TI - Stress variances among informal hospice caregivers. AB - Care interventions are not routinely provided for hospice caregivers, despite widespread documentation of the burden and toll of the caregiving experience. Assessing caregivers for team interventions (ACT) proposes that holistic patient and family care includes ongoing caregiver needs assessment of primary, secondary, and intrapsychic stressors. In this study, our goal was to describe the variance in stressors for caregivers to establish evidence for the ACT theoretical framework. We used secondary interview data from a randomized controlled trial to analyze hospice caregiver discussions about concerns. We found variances in stress types, suggesting that caregiver interventions should range from knowledge and skill building to cognitive-behavioral interventions that aid in coping. Family members who assume the role of primary caregiver for a dying loved one need to be routinely assessed by hospice providers for customized interventions. PMID- 22673094 TI - Participants' experiences of being debriefed to placebo allocation in a clinical trial. AB - Participants in placebo-controlled clinical trials give informed consent to be randomized to verum or placebo. However, researchers rarely tell participants which treatment they actually received. We interviewed 4 participants in a trial of acupuncture for irritable bowel syndrome before, during, and after they received a course of placebo treatments over 6 weeks. During the final interview, we informed participants that they had received a course of placebo treatments. We used an idiographic phenomenological approach based on the Sheffield School to describe each participant's experiences of being blinded to and then debriefed to placebo allocation. The participants' experiences of blinding and debriefing were embodied, related to their goals in undertaking the study, and social (e.g., embedded in trusting and valued relationships with acupuncturists). We suggest ways in which debriefing to placebo allocation can be managed sensitively to facilitate positive outcomes for participants. PMID- 22673095 TI - A comparative population-based study of prostate cancer incidence and mortality rates in Singapore, Sweden and Geneva, Switzerland from 1973 to 2006. AB - BACKGROUND: Prostate cancer is the most commonly diagnosed malignancy in men in Sweden and Geneva, and the third most common in men in Singapore. This population based study describes trends in the incidence and mortality rates of prostate cancer in Singapore, Sweden and Geneva (Switzerland) from 1973 to 2006 and explores possible explanations for these different trends. METHODS: Data from patients diagnosed with prostate cancer were extracted from national cancer registries in Singapore (n = 5,172), Sweden (n = 188,783) and Geneva (n = 5,755) from 1973 to 2006. Trends of incidence and mortality were reported using the Poisson and negative binomial regression models. The age, period and birth-cohort were tested as predictors of incidence and mortality rates of prostate cancer. RESULTS: Incidence rates of prostate cancer increased over all time periods for all three populations. Based on the age-period-cohort analysis, older age and later period of diagnosis were associated with a higher incidence of prostate cancer, whereas older age and earlier period were associated with higher mortality rates for prostate cancer in all three countries. CONCLUSIONS: This study demonstrated an overall increase in incidence rates and decrease in mortality rates in Singapore, Sweden and Geneva. Both incidence and mortality rates were much lower in Singapore. The period effect is a stronger predictor of incidence and mortality of prostate cancer than the birth-cohort effect. PMID- 22673096 TI - Long-term oral intake through a salivary bypass tube with chronic pharyngocutaneous fistula. AB - Pharyngocutaneous fistulae (PCFs) are a common complication after total laryngectomy. Patients with persistent PCFs are often kept nil by mouth and are dependent on feedings via a gastric tube. Our patient is a 65-year-old man who presented to our clinic in 2008 having a persistent PCF after a total laryngectomy who failed numerous attempts at reconstruction. We inserted a salivary bypass tube as a method of spanning the PCF and advanced his oral diet. He has been able to tolerate a regular diet 30 months postoperatively with no dysphagia and has gained weight. This is a demonstration of salivary bypass tubes as a useful adjunct to maintain oral intake in the presence of a persistent PCF. PMID- 22673097 TI - Videofluorographic detection of anti-muscle-specific kinase-positive myasthenia gravis. AB - A 47-year-old woman with dysphagia and ptosis gradually developed dysarthria and muscular weakness. Magnetic resonance imaging, testing for anti-acetylcholine receptor antibodies, edrophonium chloride (EC) test, and electrophysiologic test revealed no abnormalities. A psychogenic reaction was suspected. Four months after disease onset, the patient presented to our hospital. In videofluoroscopic examination of swallowing (VF), there was no aspiration for swallowing of either liquid or soft food. It revealed, however, poor pharyngeal constriction, no epiglottis inversion, repeated swallowing movements, and large amounts of pharyngeal residue. Videofluoroscopic examination of swallowing after an intravenous injection of 10 mg EC showed improvements in all above observations; particularly, it was clear when swallowing soft food. Furthermore, the anti muscle-specific kinase (MuSK) antibody titer was elevated, and anti-MuSK antibody positive myasthenia gravis (MuSK-MG) was diagnosed. Thus VF during EC test may be helpful in diagnosing MuSK-MG in patients with dysphagia. PMID- 22673098 TI - Exogenously acquired 16S rRNA methyltransferases found in aminoglycoside resistant pathogenic Gram-negative bacteria: an update. AB - Exogenously acquired 16S rRNA methyltransferase (16S-RMTase) genes responsible for a very high level of resistance against various aminoglycosides have been widely distributed among Enterobacteriaceae and glucose-nonfermentative microbes recovered from human and animal. The 16S-RMTases are classified into two subgroups, N7-G1405 16S-RMTases and N1-A1408 16S-RMTases, based on the mode of modification of 16S rRNA. Both MTases add the methyl group of S-adenosyl-L methionine (SAM) to the specific nucleotides at the A-site of 16S rRNA, which interferes with aminoglycoside binding to the target. The genetic determinants responsible for 16S-RMTase production are often mediated by mobile genetic elements like transposons and further embedded into transferable plasmids or chromosome. This genetic apparatus may thus contribute to the rapid worldwide dissemination of the resistance mechanism among pathogenic microbes. More worrisome is the fact that 16S-RMTase genes are frequently associated with other antimicrobial resistance mechanisms such as NDM-1 metallo-beta-lactamase and CTX M-type ESBLs, and some highly pathogenic microbes including Salmonella spp. have already acquired these genes. Thus far, 16S-RMTases have been reported from at least 30 countries or regions. The worldwide dissemination of 16S-RMTases is becoming a serious global concern and this implies the necessity to continue investigations on the trend of 16S-RMTases to restrict their further worldwide dissemination. PMID- 22673099 TI - The struggle of 1:1 care. PMID- 22673100 TI - Obesity: Managing an emerging health crisis. PMID- 22673101 TI - Solitary giant neurofibroma of the neck subjected to photodynamic therapy: case study. AB - Photodynamic therapy (PDT) - the fourth modality - has been successfully used in the management of early and advanced pathologies of the head and neck. We studied the effect of this modality on a giant solitary neurofibroma of the neck. A 70 year-old Caucasian female presented with left neck pain and disfigurement associated with slight shortness of breath and dysphagia. Examination revealed a large mass in the neck with no neurovascular compromise. Magnetic resonance imaging (MRI) reported a heterogeneously enhancing mass extending from the left angle of the mandible to the base of the neck. A core biopsy was performed and histopathological examination revealed a disorganised array of peripheral nerve fascicles. The patient elected to receive photodynamic therapy as the primary intervention. The multi-disciplinary meeting approved the treatment plan. The photosensitizing agent was mTHPC (0.15 mg/kg), which was systemically administered 96-hours prior to ultrasound (US)-guided light delivery to the mass, which was undertaken under general anaesthesia. Recovery was uneventful. Post-PDT follow-up showed that the patient's pain, dysphagia and shortness of breath issues had improved. The disfigurement of the neck caused by the mass was no longer a problem. Three months post-PDT, MRI revealed a significant reduction in the neurofibroma size. PDT was proven as a successful primary intervention for this pathology. However, higher evidence-based studies are required before this therapy can be proposed as a replacement to any of the other conventional therapies. PMID- 22673102 TI - Establishment of a cell line persistently infected with chronic wasting disease prions. AB - Elk prion protein (PrP(C)) has been confirmed to be capable of rendering rabbit epithelial RK13 cells permissive to temporal infection by chronic wasting disease (CWD) prions. The present study satisfactorily generated persistently CWD prion affected RK13 cells (RKC1-11) using elk PrP(C) expressing cells (elkRK13) that were generated via the lentiviral expression system with high efficiency. The elkRK13 cells have been shown to be permissive to accumulation of abnormal isoforms of prion protein (PrP(Sc)) resulting from CWD prions up to 97 serial passages thus far. This novel prion-affected cell line will help facilitate investigation of the molecular basis of CWD prion pathogenesis and confirmation of CWD prion infectivity in vitro. PMID- 22673104 TI - Antioxidant status in MgO nanoparticle-exposed rats. AB - In this present study, antioxidant status was evaluated in rat serum following exposure to magnesium oxide (MgO) nanoparticles. The lungs of rats were intratracheally instilled with (single dose) phosphate-buffered saline (PBS) + 1% of Tween 80 (solvent control) or MgO or carbonyl iron (negative control) or quartz particles (positive control) at a dose of 1 and 5 mg/kg of body weight. The blood samples were collected at 1, 7, and 30 days of postinstillation of nanoparticles after their exposure, and different parameters were estimated to assess the oxidative stress induced by the instillation of MgO. Exposure of rats to MgO produced a significant (p < 0.05) dose-dependent reduction in blood total antioxidant capacity, superoxide dismutase, and catalase activity levels than PBS + 1% Tween 80 control group. This reduction in the antioxidant capacity in MgO nanoparticle-exposed rats indicates the reduction in antioxidant defense mechanisms due to the instillation of MgO. These results indicate that exposure to MgO nanoparticles induces oxidative stress by reducing the total antioxidant capacity in rats. The findings suggest possible occupational health hazard in chronic exposures. PMID- 22673103 TI - Estimation of groin recurrence risk in patients with squamous cell vulvar carcinoma by the assessment of marker gene expression in the lymph nodes. AB - BACKGROUND: Regional lymph node (LN) status is a well-known prognostic factor for vulvar carcinoma (VC) patients. Although the reliable LN assessment in VC is crucial, it presents significant diagnostic problems. We aimed to identify specific mRNA markers of VC dissemination in the LN and to address the feasibility of predicting the risk of nodal recurrence by the patterns of gene expression. METHODS: Sentinel and inguinal LN samples from 20 patients who had undergone surgery for stage T(1-3), N(0-2), M(0) primary vulvar squamous cell carcinoma were analyzed. Gene expression profiles were assessed in four metastatic [LN(+)] and four histologically negative [LN(-)] lymph node samples obtained from four VC patients, by the Affymetrix U133 Plus 2.0 gene expression microarrays. Of the set of genes of the highest expression in the metastatic LNs compared to LN(-), seven candidate marker genes were selected: PERP, S100A8, FABP5, SFN, CA12, JUP and CSTA, and the expression levels of these genes were further analyzed by the real-time reverse transcription polymerase chain reaction (qRT-PCR) in 71 LN samples. RESULTS: All of the seven genes in question were significantly increased in LN(+) compared to LN(-) samples. In the initial validation of the seven putative markers of metastatic LN, the Cox proportional hazard model pointed to SFN, CA12 and JUP expression to significantly relate to the time to groin recurrence in VC patients. CONCLUSIONS: Our findings first provided evidence that SFN, CA12 and JUP have a potential of marker genes for the prediction of the groin recurrence LN in VC patients. PMID- 22673105 TI - Molecular frequency and isolation of cyst-forming coccidia from free ranging chickens in Bahia State, Brazil. AB - The Toxoplasmatinae parasites Toxoplasma gondii, Neospora caninum and Hammondia spp. have carnivores as definitive hosts that shed the parasite oocysts in their feces. Birds that feed directly from the soil, such as chickens, are exposed to infection and may serve as indicators of the presence of the parasite in the environment and as a source of infection for other animals. The aims of this study were to determine the frequency of infection by these parasites in free ranging chickens, to test whether chickens are intermediate hosts of Hammondia spp., and to isolate N. caninum from chickens. One hundred chickens, which were raised in contact to cattle and dogs, were bought in five towns located in Bahia, Brazil. Blood and tissues (brain and heart) were used for serology, molecular tests and bioassay in mice for parasite isolation. T. gondii DNA was detected in 29 chickens, and N. caninum DNA was observed in six animals. Hammondia spp. DNA was not detected in tissues from any chicken. Tissues from eight N. caninum seropositive chickens were bioassayed in interferon-gamma gene knockout mice, but the mice did not become infected; T. gondii was isolated from six of 14 seropositive chickens after bioassay in outbreed Swiss mice. The authors concluded that: chickens seem to be better hosts for T. gondii when compared to N. caninum, based on the molecular and bioassay results; Hammondia spp. probably does not infect chickens or is rarely found in this animal species. PMID- 22673106 TI - A PCR-based survey of selected Babesia and Theileria parasites in cattle in Sri Lanka. AB - Hemoprotozoan parasites are responsible for significant economic losses in cattle. We screened Sri Lankan cattle populations for the presence of Babesia bovis, Babesia bigemina, Theileria annulata, and Theileria orientalis, using species-specific PCR assays. Out of 316 samples collected from animals in four different districts of Sri Lanka (Nuwara Eliya, Polonnaruwa, Ampara, and Jaffna), 231 (73.1%) were positive for at least one parasite species. All four parasite species were detected among the study groups from all of the districts surveyed. The first and second commonest hemoprotozoan parasites identified were T. orientalis (53.5%) and B. bigemina (30.1%), respectively. We found that the dry zones (Polonnaruwa, Ampara, and Jaffna) had more Babesia-positive animals than the hill country wet zone (Nuwara Eliya). In contrast, T. orientalis was the predominant species detected in Nuwara Eliya, while infection with T. annulata was more common in the dry zones. In addition, 81 (35.1%) of the 231 positive samples were infected with more than one parasite species. The presence of multiple parasite species among the different cattle populations is of clinical and economic significance. Therefore, island-wide control and prevention programs against bovine babesiosis and theileriosis are needed to minimize the financial burden caused by these parasites. PMID- 22673107 TI - Efficacy of two avermectins, doramectin and ivermectin against Argulus siamensis infestation in Indian major carp, Labeo rohita. AB - The efficacy of two avermectins, doramectin and ivermectin via oral and parenteral routes and their prophylactic effects against Argulus siamensis infestation in Indian major carp, Labeo rohita was studied. Doramectin and ivermectin were fed once to L. rohita sub-adults naturally infested with A. siamensis parasites at graded levels of 1000, 750 and 500 MUg/kg body weight and 500, 300 and 200 MUg/kg body weight, respectively. The mean time of clearance of parasites was 24 +/- 0.149 h for 1000 and 24 +/- 0.210 h for 750 MUg of doramectin/kg body weight fish, however, the dose of 1,000 MUg resulted in adverse reactions and mortality in fish. A single dose of 500MUg/kg body weight of ivermectin also cleared the infestation in 24 +/- 0.258 h. In second experiment, L. rohita naturally infested with A. siamensis were administered with doramectin and ivermectin intramuscularly as single dose of 200, 150 and 100 MUg/kg body weight. Both doramectin and ivermectin at 200 MUg/kg body weight cleared the infestation in 4 +/- 0.149 and 4 +/- 0.258 h respectively, however, those resulted in adverse reactions viz., black pigmentation, lethargy and poor appetite in fish. The mean time of clearance of parasites from fish was 6 +/- 0.210 and 12 +/- 0.314 h for doramectin and ivermectin, respectively, when given at a lower dose of 150 MUg/kg body weight. The prophylactic effects of both drugs were also evaluated by challenging naive rohu with metanaupliar larvae of A. siamensis after feeding the fish single dose of the doramectin and ivermectin at 750 and 500 MUg/kg body weight, respectively. The effects of both the drugs were found to last for 17-18 days. The effects of bath treatment with doramectin and ivermectin at different concentrations on adult A. siamensis and metanaupliar larvae of A. siamensis were also evaluated. The results suggested that ivermectin could act more rapidly compared to doramectin. However, detailed studies on the toxicity and pharmacokinetics of doramectin and ivermectin upon their administration to aquatic organisms and the environmental impacts of their usage are required to be undertaken before finally recommending the safe use of these drugs for control of parasitic infections. PMID- 22673108 TI - Oral sex, cancer and death: sexually transmitted cancers. AB - We briefly highlight the growing body of recent evidence linking unprotected oral sex with the development of some types of head and neck cancer in younger patients. These tumours appear to be increasing in incidence although the development of more sensitive methods of HPV detection may be a confounding factor. PMID- 22673109 TI - Genetic and genomic glimpses of the elusive arbuscular mycorrhizal fungi. AB - Arbuscular mycorrhizal fungi (AMF), which form an ancient and widespread mutualistic symbiosis with plants, are a crucial but still enigmatic component of the plant microbiome. Nowadays, their obligate biotrophy is no longer an obstacle to deciphering the role played by AMF in this fascinating symbiosis. The first genome-wide transcriptomic analysis of an AMF showed a metabolic complexity with no sign of massive gene loss, and the presence of genes for meiotic recombination suggests that AMF are not simple clonal organisms, as originally thought. New findings on suppression of host defenses and nutrient exchange processes have shed light on the mechanisms that contribute to such an intimate and long-lasting integration between living plant and fungal cells. PMID- 22673111 TI - Biological effects of chicken type III interferon on expression of interferon stimulated genes in chickens: comparison with type I and type II interferons. AB - Interferons (IFNs) are key mediators that activate host defense mechanisms against viruses. The recently identified mammalian Type III IFN has biological effects similar to type I IFN. However, the biological effects of type III IFN have not yet been characterized in birds. We compared the effects of chicken type III IFN (IFN-lambda) with type I (IFN-beta) and type II (IFN-gamma) IFNs on IFN stimulated genes (ISGs) using recombinant proteins expressed in Escherichia coli. Recombinant chicken IFN-lambda inhibited influenza virus replication and induced the mRNA expression of the ISGs, Mx and OAS, in chicken embryonic fibroblasts (CEFs) in a dose-dependent manner. However, the effective dose of IFN-lambda was higher than that of IFN-beta and IFN-gamma. Furthermore, the effect of IFN-lambda on induction of Mx and OAS was lesser than that of IFN-beta, but comparable to that of IFN-gamma. These results indicate that chicken IFN-lambda has the potential to induce ISGs and inhibit viral replication in chicken cells. PMID- 22673110 TI - Characterization of a biogas-producing microbial community by short-read next generation DNA sequencing. AB - BACKGROUND: Renewable energy production is currently a major issue worldwide. Biogas is a promising renewable energy carrier as the technology of its production combines the elimination of organic waste with the formation of a versatile energy carrier, methane. In consequence of the complexity of the microbial communities and metabolic pathways involved the biotechnology of the microbiological process leading to biogas production is poorly understood. Metagenomic approaches are suitable means of addressing related questions. In the present work a novel high-throughput technique was tested for its benefits in resolving the functional and taxonomical complexity of such microbial consortia. RESULTS: It was demonstrated that the extremely parallel SOLiDTM short-read DNA sequencing platform is capable of providing sufficient useful information to decipher the systematic and functional contexts within a biogas-producing community. Although this technology has not been employed to address such problems previously, the data obtained compare well with those from similar high throughput approaches such as 454-pyrosequencing GS FLX or Titanium. The predominant microbes contributing to the decomposition of organic matter include members of the Eubacteria, class Clostridia, order Clostridiales, family Clostridiaceae. Bacteria belonging in other systematic groups contribute to the diversity of the microbial consortium. Archaea comprise a remarkably small minority in this community, given their crucial role in biogas production. Among the Archaea, the predominant order is the Methanomicrobiales and the most abundant species is Methanoculleus marisnigri. The Methanomicrobiales are hydrogenotrophic methanogens. Besides corroborating earlier findings on the significance of the contribution of the Clostridia to organic substrate decomposition, the results demonstrate the importance of the metabolism of hydrogen within the biogas producing microbial community. CONCLUSIONS: Both microbiological diversity and the regulatory role of the hydrogen metabolism appear to be the driving forces optimizing biogas-producing microbial communities. The findings may allow a rational design of these communities to promote greater efficacy in large-scale practical systems. The composition of an optimal biogas-producing consortium can be determined through the use of this approach, and this systematic methodology allows the design of the optimal microbial community structure for any biogas plant. In this way, metagenomic studies can contribute to significant progress in the efficacy and economic improvement of biogas production. PMID- 22673112 TI - Genetic variation in galectin-3 gene associates with cognitive function at old age. AB - Inflammation plays an important role in the development of cognitive decline and dementia in old age. Galectin-3 is known for its role in acute and chronic inflammation. We assessed whether genetic variation in the LGALS3 gene, encoding for galectin-3, associates with cognitive function in the 5804 participants of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). The rs4644, rs4652, and rs1009977 polymorphisms were genotyped to cover the genomic region of the LGALS3 gene. Subjects carrying the variant alleles of each LGALS3 single nucleotide polymorphism (SNP) had significantly higher baseline C-reactive protein concentrations (p < 0.01). Carriers of the variant alleles had significantly worse performance at baseline compared with carriers of the wild type allele (all p < 0.05). In the longitudinal analysis, we found that carriers of the variant alleles had worse performance at the attention tasks compared with carriers of the wild-type allele. Although observed differences were small, these data suggest that genetic variation in the LGALS3 gene might be associated with cognitive function in an elderly population. Further research is warranted to confirm these results. PMID- 22673113 TI - A hexanucleotide repeat expansion in C9ORF72 causes familial and sporadic ALS in Taiwan. AB - A GGGGCC hexanucleotide repeat expansion in the C9ORF72 gene was recently identified as an important cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia in Caucasian populations. The role of the C9ORF72 repeat expansion in ALS in Chinese populations has received little attention. We therefore performed mutation analyses in a Taiwanese cohort of 22 unrelated familial ALS (FALS) patients and 102 sporadic ALS patients of Han Chinese descent. The C9ORF72 mutation was found in 4 FALS (18.2%; 4/22) and 2 sporadic ALS patients (2.0%; 2/102). The C9ORF72 repeat numbers in the 300 healthy controls and the 118 ALS patients without the C9ORF72 mutation ranged from 3 to 15. Needle biopsy in the left frontal cortex of 1 patient with FALS frontotemporal dementia revealed numerous cytoplasmic TAR DNA-binding protein 43 (TDP-43) inclusions and minimal neuritis, consistent with type B frontotemporal lobar degeneration with TDP-43 (FTLD-TDP) pathology. This study clearly demonstrates the existence and importance of the C9ORF72 hexanucleotide repeat expansion in a Taiwanese ALS cohort of Chinese origin, and supports the global presence of the C9ORF72 repeat expansion in ALS. PMID- 22673114 TI - Abeta leads to Ca2+ signaling alterations and transcriptional changes in glial cells. AB - The pathogenesis of Alzheimer's disease includes accumulation of toxic amyloid beta (Abeta) peptides. A recently developed cell-permeable peptide, termed Tat Pro, disrupts the complex between synapse-associated protein 97 (SAP97) and the alpha-secretase a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10), thereby leading to an alteration of the trafficking of the enzyme, which is important for nonamyloidogenic processing of amyloid precursor protein (APP). We report that Tat-Pro treatment, as well as the treatment with exogenous Abeta, deregulates Ca(2+) homeostasis specifically in astrocytes through increased expression of key components of Ca(2+) signaling, metabotropic glutamate receptor-5 and inositol 1,4,5-trisphosphate receptor-1. This is accompanied by potentiation of (S)-3,5-dihydroxyphenylglycine-induced Ca(2+) transients. Calcineurin inhibition reverts all these effects. Furthermore, our data demonstrate that astrocytes express all the components for the amyloidogenic and nonamyloidogenic processing of APP including APP itself, beta-site APP cleaving enzyme 1 (BACE1), ADAM10, gamma-secretase, and SAP97. Indeed, treatment with Tat-Pro for 48 hours significantly increased the amount of Abeta(1-42) in the medium of cultured astrocytes. Taken together, our results suggest that astroglia might be active players in Abeta production and indicate that the calcium hypothesis of Alzheimer's disease may recognize glial cells as important intermediates. PMID- 22673116 TI - Differential effect of troglitazone on the human bile acid transporters, MRP2 and BSEP, in the PXB hepatic chimeric mouse. AB - The aims of this study were to assess the utility of the PXB mouse model of a chimeric human/mouse liver in studying human-specific effects of an important human hepatotoxic drug, the PPARgamma agonist, troglitazone. When given orally by gavage for 7 days, at dose levels of 300 and 600 ppm, troglitazone induced specific changes in the human hepatocytes of the chimeric liver without an effect on the murine hepatic portions. The human hepatocytes, in the vehicle-treated PXB mouse, showed an accumulation of electron-dense lipid droplets that appeared as clear vacuoles under the light microscope in H&E-stained sections. Following dosing with troglitazone, there was a loss of the large lipid droplets in the human hepatocytes, a decrease in the amount of lipid as observed in frozen sections of liver stained by Oil-red-O, and a decrease in the expression of two bile acid transporters, BSEP and MRP2. None of these changes were observed in the murine remnants of the chimeric liver. No changes were observed in the expression of three CYPs, CYP 3A2, CYP 1A1, and CYP 2B1, in either the human or murine hepatocytes, even though the baseline expression of the enzymes differed significantly between the two hepatocyte species with the mouse hepatocytes consistently showing increased expression of the protein of all three enzymes. This study has shown that the human hepatocytes, in the PXB chimeric mouse liver, retain an essentially normal phenotype in the mouse liver and, the albeit limited CYP enzymes studied show a more human, rather than a murine, expression pattern. In line with this conclusion, the study has shown a differential response of the human versus the mouse hepatocytes, and the effects observed are highly suggestive of a differential handling of the compound by the two hepatocyte species although the exact reasons are not as yet clear. The PXB chimeric mouse system therefore holds the clear potential to explore human hepatic-specific features, such as metabolism, prior to dosing human subjects, and as such should have considerable utility in drug discovery and development. PMID- 22673117 TI - Epidemiologic investigation of burns in the elderly in Sichuan Province. AB - OBJECTIVE: This study analysed the epidemiology of burns in the elderly in Sichuan Province, China, with the objective of formulating a prevention programme. METHODS: A retrospective review of elderly patients admitted to the Burn Centre of West China Hospital during 2003-2009 was performed, including patient demographics, education and burn aetiology. RESULTS: A total of 103 patients, mean age 69.5 years (range 60-95 years; 58 male, 45 female) were admitted. The most common causes of burn were flames (51.5%), scalding (37.9%), electrical (4.9%) and chemical (2.9%), respectively. The majority occurred at home (68.9%), principally in the kitchen (35.9%), while 19.4% occurred in the workplace. Burns with total body surface area (TBSA) of 0-10% accounted for 52.5% of those admitted for treatment; 10-30% TBSA burns accounted for 20.3%; 30-50% TBSA burns accounted for 15.5%; and burns with a TBSA >50% accounted for 11.7%. Only 6% of patients received appropriate first aid, and 32% did not receive treatment until more than 24h after injury. The education level was lower in the rural group. Both urban and rural groups had little knowledge of first aid for burns. CONCLUSIONS: Burn-prevention programmes should promote improved living conditions and medical insurance, with prevention education for the elderly, especially in rural areas. PMID- 22673115 TI - Identification of Alzheimer disease-associated variants in genes that regulate retromer function. AB - The proteolytic processing of amyloid precursor protein (APP) to generate the neurotoxic amyloid beta (Abeta) peptide is central to the pathogenesis of Alzheimer disease (AD). The endocytic system mediates the processing of APP by controlling its access to secretases that cleave APP. A key mediator of APP localization is SorL1-a membrane protein that has been genetically linked to AD. The retromer complex is a conserved protein complex required for endosome-to Golgi retrieval of a number of physiologically important membrane proteins including SorL1. Based on the prior suggestion that endocytosis and retromer sorting pathways might be involved, we hypothesized that variants in other genes in this pathway might also modulate AD risk. Genetic association of AD with 451 polymorphisms in 15 genes encoding retromer or retromer-associated proteins was tested in a Caucasian sample of 8309 AD cases and 7366 cognitively normal elders using individual single nucleotide polymorphism (SNP)- and gene-based tests. We obtained significant evidence of association with KIAA1033 (VEGAS p = 0.025), SNX1 (VEGAS p = 0.035), SNX3 (p = 0.0057), and RAB7A (VEGAS p = 0.018). Ten KIAA1033 SNPs were also significantly associated with AD in a group of African Americans (513 AD cases, 504 control subjects). Findings with four significant SNX3 SNPs in the discovery sample were replicated in a community-based sample of Israeli-Arabs (124 AD cases, 142 control subjects). We show that Snx3 and Rab7A proteins interact with the cargo-selective retromer complex through independent mechanisms to regulate the membrane association of retromer and thereby are key mediators of retromer function. These data implicate additional AD risk genes in the retromer pathway and formally demonstrate a direct link between the activity of the retromer complex and the pathogenesis of AD. PMID- 22673118 TI - Incidence and treatment of burns: a twenty-year experience from a single center in Germany. AB - OBJECTIVE: To analyze trends in incidence and treatment of thermal injuries over the last two decades. METHODS: We retrospectively reviewed our local single center database of patients with thermal injuries admitted to the burn intensive care unit (BICU) of the Cologne-Merheim Medical Center (University Hospital of Witten/Herdecke). The cohort was divided into two groups according to the decade of admission and the epidemiology and clinical course of the patient sample admitted during the period 1991-2000 (n=911) was compared to that of 2001-2010 (n=695). RESULTS: The following variables were significantly different in the bivariate analysis: mean age (39.8 years vs. 44.0 years), burn size of total body surface area (23.2% vs. 18.0%) and size of 3rd degree burns (9.6% vs. 14.9%). The incidence of inhalation injury was significantly lower in the last decade (33.3% vs. 13.7%) and was associated with a shorter duration of mechanical ventilation (10.8 days vs. 8.5 days). The ABSI-score as an indicator of burn severity declined in the second period (6.3 vs. 6.0) contributing partially to the decline of BICU length of stay (19.1 days vs. 18.8 days) and to the mortality rate decrease (18.6% vs. 15.0%). CONCLUSION: The severity of burn injuries during the last two decades declined, probably reflecting the success of prevention campaigns. Concerning mortality, the chance of dying for a given severity of injury has decreased. PMID- 22673119 TI - Values of patients and caregivers for donor site scars: an inter-observer analysis between patients and caregivers and prediction of cosmetic satisfaction. AB - BACKGROUND: The Patient and Observer Scar Assessment Scale (POSAS) is used to judge scars and involves patients and caregivers. Although the opinions of both are integrated, agreement between them is poorly investigated, especially in donor site scars (DSSs). Furthermore, it is unknown which POSAS-items are mostly associated with overall cosmetic satisfaction with the scar. METHODS: We included 106 DSS-patients. Twelve weeks after wound healing, patients and caregivers rated the DSS in vivo using the POSAS, comprising seven items. They were unaware of each other's judgment. Inter-observer reliability (IOR) was expressed as intra class correlation coefficients (ICC). Items of the POSAS that best predicted patients' overall satisfaction were identified using multivariable regression analysis. RESULTS: Eleven caregivers from different medical centers judged the DSSs. IOR for the POSAS items was 'moderate' at best regarding the item 'overall opinion' (ICC 0.44; 95% confidence interval 0.27-0.58). IORs regarding other POSAS-items were 'poor'. Itching and relief best predicted patients' overall satisfaction (total variance explained, R(2)=0.174). For caregivers, pigmentation and pliability were most predictive (R(2)=0.318). CONCLUSION: Patients and caregivers appreciate different aspects of scar characteristics using the POSAS. This calls for shared decision-making, in which patient opinions are incorporated in the treatment choice. PMID- 22673120 TI - Dietary fiber and mortality: convincing observations that call for mechanistic investigations. PMID- 22673121 TI - Diagnostic values of ultrasound and the Modified Alvarado Scoring System in acute appendicitis. AB - BACKGROUND: Making the diagnosis of acute appendicitis is difficult, and is important for preventing perforation of the appendix and negative appendectomy results. Ultrasound and clinical scoring systems are very helpful in making the diagnosis. Ultrasound is non-invasive, available and cost-effective, and can accomplish more than CT scans. However, there is no certainty about its effect on the clinical outcomes of patients, and it is operator dependent. Counting the neutrophils as a parameter of the Alvarado Scale is not routine in many laboratories, so we decided to evaluate the diagnostic value of the Modified Alvarado Scaling System (MASS) by omitting the neutrophil count and ultrasonography. METHODS: After ethical approval of methodology in Tehran University of Medical Sciences ethical committee, we collected the data. During 9 months, 75 patients with right lower quadrant pain were enrolled in the study, and underwent abdominal ultrasonography and appendectomy, with pathological evaluation of the appendix. The MASS score was calculated for these patients and compared with pathology results. RESULTS: Fifty-five male and 20 female patients were assessed. Of these patients 89.3% had acute appendicitis. The sensitivity, specificity, PPV, NPV and accuracy rate of ultrasonography was 71.2%, 83.3%, 97.4%, 25% and 72.4%, respectively. By taking a cutoff point of 7 for the MASS score, a sensitivity of 65.7%, specificity of 37.5%, PPV of 89.8%, NPV of 11.5% and accuracy of 62.7% were calculated. Using the cutoff point of 6, a sensitivity of 85.1%, specificity of 25%, PPV of 90.5%, NPV of 16.7% and accuracy of 78.7% were obtained. CONCLUSION: Ultrasound provides reliable findings for helping to diagnose acute appendicitis in our hospital. A cutoff point of 6 for the MASS score will yield more sensitivity and a better diagnosis of appendicitis, though with an increase in negative appendectomy. PMID- 22673123 TI - Occurrence and removal of polycyclic aromatic hydrocarbons in the wastewater treatment process. AB - The occurrence and removal of polycyclic aromatic hydrocarbons (PAHs) was examined at different stages at a modified anaerobic-anoxic-oxic biological wastewater treatment plant in Tai'an City in eastern China. Twelve PAHs were detectable, with low molecular weight PAHs found at different treatment stages in wastewater and sludge. The most frequent and abundant PAHs in the influents were different in May and November. In May, 3- and 4-ringed PAH compounds were predominant, accounting for 53.5% of the ?PAHs. However, in November, 2-ringed PAH compounds were most frequent and abundant, accounting for 90.1% of the ?PAHs. In May and November, the removal efficiencies of individual PAH compounds ranged from 72.4 to 99.4% and from 21.1% to 100%, respectively, in the total treatment process. A significant relationship was observed between the removal efficiency and log K(ow) of the PAH compounds in the grit stage (when the values of log K(ow) were higher than approximately 5), suggesting that these compounds were principally removed through sorption to sludge particles and transfer to sludge processing systems. The residence time impacted the removal efficiency in the biological treatment process at the primary and secondary stages. In addition, the removal efficiencies depended dramatically on seasonal variations. PMID- 22673124 TI - Polycyclic aromatic hydrocarbons and organochlorine pesticides in fish from Taihu Lake: their levels, sources, and biomagnification. AB - The investigation of biomagnification of polycyclic aromatic hydrocarbons (PAHs) and endosulfan, an organochlorine pesticide (OCP) and a new persistent organic pollutant, has been limited in freshwater food chains. The objective of the present study was to investigate the levels with focus on the sources and biomagnification of PAHs and OCPs in fish from Taihu Lake, China. In 193 samples of 24 species investigated, the concentrations ranged from 289 to 9 500 ng/g lipid weight (lw) for PAHs, and from 121 to 904 ng/g lw for OCPs, indicating that the fish in the lake was moderately contaminated. The PAHs mainly originated from both unburned petroleum and combustion of fossil fuels, and the OCPs from aged residues. It was unlikely that most of the PAHs and OCPs were biodiluted through the food chain because their trophic magnification factors were higher than one nevertheless the P-values >0.05. Aldrin, dieldrin, p,p'-DDE, p,p'-DDD, and endosulfan sulfate were significantly biomagnified through the food chain. PMID- 22673125 TI - When the problem is beneath the surface in OCD: the cognitive treatment of a case of pure mental contamination. AB - BACKGROUND: Mental contamination is a phenomenon whereby people experience feelings of contamination from a non-physical contaminant. Rachman (2006) proposes that standard cognitive behavioural treatments (CBT) need to be adapted here and there is a developing empirical grounding supporting the concept, although suggestions on adapting treatment have yet to be tested. METHOD: A single case study is presented of a man with a 20-year history of severe treatment resistant Obsessive Compulsive Disorder (OCD) characterized by mental contamination following the experience of "betrayal". He was offered two consecutive treatments: standard CBT and then (following disengagement with this) a cognitive therapy variant adapted for mental contamination. Clinician and patient rated OCD severity was measured at baseline and the start and end of both interventions. RESULTS: Six sessions of high quality CBT were initially attended before refusal to engage with further sessions. There were no changes in OCD severity ratings across these sessions. A second course of cognitive therapy adapted for mental contamination was then offered and all 14 sessions and follow ups were attended. OCD severity fell from the severe to non-clinical range across these sessions. CONCLUSIONS: The need to consider adapting standard treatments for mental contamination is suggested. Limitations and implications are discussed. PMID- 22673126 TI - Cognitive and non-cognitive factors associated with posttraumatic stress symptoms in mothers of children with type 1 diabetes. AB - BACKGROUND: The experience of having a child diagnosed with type 1 diabetes mellitus (T1DM) can negatively impact on the mother's well-being and trigger posttraumatic stress symptoms. To date, only one study has examined the role of non-cognitive factors in predicting the occurrence of PTSD in parents of children diagnosed with diabetes. However, in the broader PTSD literature is has been shown that both non-cognitive variables and cognitive variables predict PTSD in traumatized populations. AIMS: The current study aimed to investigate the relationship of both non-cognitive (trauma severity, psychiatric history and social support) and cognitive variables (negative cognitive appraisals and dysfunctional cognitive appraisals) with PTSD in mothers of children recently diagnosed with diabetes. METHOD: A single group survey design and self-report questionnaires were used to investigate the relationship between both non cognitive (trauma severity, psychiatric history and history of trauma, and social support) and cognitive factors (negative cognitive appraisals and dysfunctional strategies) and PTSD symptoms in mothers of children who had been diagnosed with type 1 diabetes in the last 5 years. RESULTS: All cognitive variables were positively associated with PTSD symptoms. In contrast, of the non-cognitive variables, only social support was significantly (negatively) associated with PTSD symptoms. Moreover, regression analysis found that cognitive variables explained variance in PTSD symptoms over and above that contributed by the non cognitive variables. CONCLUSIONS: This supports the cognitive model of PTSD. The implications of the study with regards to early detection of and therapies for PTSD in this population are discussed. PMID- 22673127 TI - Persistence, perseveration and perfectionism in the eating disorders. AB - BACKGROUND: Perseveration, persistence and perfectionism are traits that have been suggested to be relevant to the eating disorders. This study explored the levels and correlates of these three traits in the eating disorders and control groups. METHOD: A measure of these three elements (the Persistence, Perseveration and Perfectionism Questionnaire - PPPQ-22) was administered to 99 women with eating disorders, 25 women with other psychiatric disorders, and 91 non-clinical women. Differences in PPPQ-22 scores across groups were measured, as were the associations between PPPQ-22 scores and eating attitudes. RESULTS: The eating disordered groups showed lower levels of persistence (the drive towards goal achievement) than the non-clinical group, but did not show higher levels of perseveration (the following of rules, without considering whether goals are achieved). Both women with eating disorders and non-clinical controls showed correlations between eating disorder symptoms and perseveration. CONCLUSIONS: The current study, using a relatively new measure, suggests that low levels of persistence, rather than high levels of perseveration, may be implicated in the eating disorders. It was less clear that perfectionism per se was a useful construct in understanding eating pathology. If confirmed by future research, persistence should be considered in treatment of these complex and challenging conditions. PMID- 22673128 TI - A fatal course of neonatal meningo-encephalitis. PMID- 22673130 TI - The tale of the wandering circumflex. PMID- 22673129 TI - Monitoring seasonal influenza A evolution: rapid 2009 pandemic H1N1 surveillance with an reverse transcription-polymerase chain reaction/electro-spray ionization mass spectrometry assay. AB - BACKGROUND: The emergence of the pandemic H1N1 influenza strain in 2009 reinforced the need for improved influenza surveillance efforts. A previously described influenza typing assay that utilizes RT-PCR coupled to electro-spray ionization mass spectrometry (ESI-MS) played an early role in the discovery of the pandemic H1N1 influenza strain, and has potential application for monitoring viral genetic diversity in ongoing influenza surveillance efforts. OBJECTIVES: To determine the analytical sensitivity of RT-PCR/ESI-MS influenza typing assay for identifying the pandemic H1N1 strain and describe its ability to assess viral genetic diversity. STUDY DESIGN: Two sets of pandemic H1N1 samples, 190 collected between April and June of 2009, and 69 collected between October 2009 and January 2010, were processed by the RT-PCR/ESI-MS influenza typing assay, and the spectral results were compared to reference laboratory results and historical sequencing data from the Nucleotide Database of the National Center for Biotechnology Information (NCBI). RESULTS: Strain typing concordance with reference standard testing was 100% in both sample sets, and the assay demonstrated a significant increase in influenza genetic diversity, from 10.5% non-wildtype genotypes in early samples to 69.9% in late samples (P<0.001). An NCBI search demonstrated a similar increase, from 13.4% to 45.2% (P<0.001). CONCLUSIONS: This comparison of early versus late influenza samples analyzed by RT-PCR/ESI-MS demonstrates the influenza typing assay's ability as a universal influenza detection platform to provide high-fidelity pH1N1 strain identification over time, despite increasing genetic diversity in the circulating virus. The genotyping data can also be leveraged for high-throughput influenza surveillance. PMID- 22673131 TI - Effect of clonidine on renal sodium handling in spontaneously hypertensive rats. AB - Up-regulation of kidney alpha2-adrenoceptor expression has been implicated in the development of hypertension in spontaneously hypertensive rats (SHR). This study was carried out to evaluate renal sodium excretion in response to clonidine administration in SHR and control normotensive Wistar-Kyoto (WKY) rats. SHR and WKY rats (12-week-old) were placed in metabolic cages for 4 days: the first 2 days in control conditions and the following 2 days under oral clonidine treatment (100 MUg/kg body weight). Clonidine produced a similar reduction in systolic blood pressure values in SHR and WKY rats, although SHR remained hypertensive. At the end of the study SHR and WKY rats presented similar noradrenaline plasma levels. However, noradrenaline kidney tissue levels were significantly higher in SHR compared to WKY rats. Under control conditions, SHR presented lower urine flow compared to WKY rats. Clonidine produced a significant decrease in urine flow in WKY rats but not in SHR. Furthermore, clonidine also produced a significant reduction in urinary sodium, potassium, and creatinine excretion in WKY rats, but had no effect in SHR. In conclusion, in SHR the reduction in systolic blood pressure and sympathetic activity produced by clonidine was not accompanied by a decrease in urine volume and sodium excretion. PMID- 22673132 TI - The mechanism of calcitonin gene-related peptide-containing nerve innervation. AB - Calcitonin gene-related peptide (CGRP) is a major neurotransmitter and CGRP containing primary sensory neurons play an important role in nociception and potent vasodilation. CGRP-containing nerves in mesenteric arteries are decreased in pathological animal models (hypertension, diabetes, and atherosclerosis). In apolipoprotein E–knockout mice, which have atherosclerosis and peripheral sensory nerve defects, nerve growth factor (NGF)-mediated CGRP nerve facilitation was down-regulated, which may have been caused by the impairment of the Akt–NO–cGMP pathway. In addition, NGF-mediated CGRP neurite outgrowth was decreased in fructose-induced insulin-resistant rats. We recently discovered that renin–angiotensin inhibitors improved CGRP innervation in spontaneously hypertensive rats, indicating that rescuing CGRP nerve innervation might improve pathophysiological conditions. To find a novel reagent that facilitates CGRP nerves, a new model, phenol-injured perivascular nerve model rats, was established. Adrenomedullin, hepatocyte growth factor, and angiotensin II type 2 receptor activation induced CGRP nerve distribution in phenol-injured rats. Furthermore, in insulin-resistant model rats, the down-regulation of CGRP nerves was likely due to the depression of phosphoinositide 3-kinase (PI3K) dependent Akt activation. Administration of candesartan improves CGRPergic function via the PI3K–Akt pathway in insulin-resistant rats. Thus, clarification of the mechanisms of CGRP nerve defects may constitute future therapeutic targets. PMID- 22673133 TI - [Pasteurella multocida septic shock in a previously healthy man]. PMID- 22673134 TI - [Primary graft dysfunction after lung transplantation]. AB - Lung transplantation is a therapeutic option for pulmonary diseases in which the other treatment options have failed or in cases of rapid disease progression. However, transplantation is not free from complications, and primary graft dysfunction is one of them. Primary graft dysfunction is a form of acute lung injury. It characteristically develops during the immediate postoperative period, being associated to high morbidity and mortality, and increased risk of bronchiolitis obliterans. Different terms have been used in reference to primary graft dysfunction, leading to a consensus document to clarify the definition in 2005. This consensus document regards primary graft dysfunction as non cardiogenic pulmonary edema developing within 72 hours of reperfusion and intrinsically attributable to alteration of the lung parenchyma. A number of studies have attempted to identify risk factors and to establish the underlying physiopathology, with a view to developing potential therapeutic options. Such options include nitric oxide and pulmonary surfactant together with supportive measures such as mechanical ventilation or oxygenation bypass. PMID- 22673135 TI - Clinical and translational research: nursing scientists at the core. PMID- 22673136 TI - Spontaneous showering of tumor emboli in a patient with advanced primary lung cancer: a case report. AB - Extension of primary lung tumors into the left atrium via pulmonary veins is a well-documented phenomenon. Peripheral arterial embolism and cerebral embolism originating from a primary lung neoplasm are rare events. We report a case of simultaneous acute bilateral lower limb ischemia, bilateral renal infarction, splenic infarction and cerebral infarction as a result of multiple emboli originating from primary lung malignancy invasion of the left atrium. An emergent embolectomy revealed pathologic features of the extracted thrombus that were identical to the pulmonary neoplasm. PMID- 22673137 TI - Eradication of invasive pneumococcal disease due to the seven-valent pneumococcal conjugate vaccine serotypes in Calgary, Alberta. AB - BACKGROUND: The seven-valent pneumococcal conjugate vaccine (PCV7) was licensed in Canada in 2001. Routine infant vaccination programs in Alberta began in 2002. Several years after PCV7 introduction, the routine use of PCV7 in infants and high-risk children has led to near elimination of invasive pneumococcal disease (IPD) caused by vaccine serotypes. METHODS: Prospective, population-based surveillance of all IPD cases was conducted from January 1998 to December 2010. Demographic, clinical and microbiologic data were collected. RESULTS: There were 1462 IPD cases over 13 years. Comparing PCV7 serotype IPD incidence in the prevaccine period (1998-2001) to the late postvaccine period (2007-2010), there were declines in children 0-5 months (100%), 6-23 months (98%), 2-4 years (97%), 5-15 years (100%) as well as in adults 16-64 years (73%), 65-84 years (90%) and >=85 years of age (100%). From 2008 to 2010, there were no cases of PCV7 serotype IPD in children under 2 years of age. There have been increases in non-PCV7 serotype IPD; notably, serotypes 5 and 19A have increased significantly in adults and 19A in children. CONCLUSIONS: PCV7 serotype IPD has been eliminated in vaccine-eligible young children and nearly eliminated in all other age groups. Serotype 19A increased significantly at all ages before the introduction of an expanded valency pneumococcal conjugate vaccine. PMID- 22673138 TI - Evaluating the usefulness of retesting for beta-lactam allergy in children. AB - Many children with adverse reactions to beta-lactams are labeled as allergic without performing an allergy study to confirm it. In this retrospective study of 10 years, we detected only 3.3% positive cases. Although international guidelines recommend a second allergy workup in patients with a negative study, we found from our results a low profitability of retesting. PMID- 22673139 TI - Persistence of antibody response following a booster dose of Hib-MenC-TT glycoconjugate vaccine to five years: a follow-up study. AB - BACKGROUND: Antibodies against Haemophilus influenzae type b (Hib) and serogroup C Neisseria meningitidis (MenC) persist better to 31/2 years of age after a 12 month booster dose of a combination Hib-MenC glycoconjugate vaccine (Hib-MenC-TT) in children primed in infancy with Hib-MenC-TT and diphtheria-tetanus-acellular pertussis-inactivated poliovirus vaccine (DTaP-IPV) than in those who received a monovalent MenC-CRM197 and DTaP-IPV-Hib (also TT conjugated). Pertussis antibodies against filamentous hemagglutinin and pertactin are higher at 5 and 12 months in children who received DTaP-IPV compared with those immunized with DTaP IPV-Hib. We evaluated whether these differences persisted to later childhood, following a preschool booster of DTaP-IPV at 31/2 years of age. METHODS: Children in the United Kingdom and Poland previously enrolled in the aforementioned randomized-controlled trial had a blood sample taken at 5 years of age. Antipolyribosylribitol phosphate (Hib) IgG and MenC bactericidal antibody (baby rabbit complement) titers were compared between those immunized in infancy (at 2, 3 and 4 months) with DTaP-IPV/Hib-MenC-TT (Hib-MenC-TT group) and those who received DTaP-IPV-Hib with a monovalent MenC-CRM197 (control group). Antibody concentrations against filamentous hemagglutinin, pertactin and pertussis toxin were also measured at this visit. RESULTS: Two hundred sixty-eight participants aged 58-64 months were enrolled. MenC baby rabbit complement titers >=1:8 were seen in 115 of 194 of the Hib-MenC-TT group (59.3% [52.0-66.3%]) and 26 of 58 (44.8% [31.7-58.5%]) of control group participants. MenC baby rabbit complement geometric mean titers were 30.4 and 11.3, respectively (ratio 2.70 [1.55- .73]). Antipolyribosylribitol phosphate (Hib) IgG concentrations >= 1.0 MUg/mL were seen in 171 of 197 (86.8% [81.3-91.2%]) of the Hib-MenC-TT group and 36 of 58 (62.1% [48.4-74.5%]) of control group participants. Antipolyribosylribitol phosphate IgG geometric mean concentrations (GMCs) were 3.82 and 1.67, respectively (ratio 2.29 [1.59-3.28]). Sixty-eight UK participants aged 58-63 months had sera analyzed for the pertussis antigens (44 DTaP-IPV recipients, 14 DTaP-IPV-Hib recipients). Antipertussis toxin IgG GMCs were similar for participants immunized with DTaP IPV and DTaP-IPV-Hib: 8.2 EL.U/mL (6.1 - 10.9) compared with 7.2 EL.U/mL (3.9 - 13.4). Antifilamentous hemagglutinin IgG GMCs were higher for DTaP-IPV recipients (164.7 EL.U/mL [119.4-227.1]) compared with DTaP-IPV-Hib recipients (66.8 EL.U/mL [43.8-101.7]), as were antipertactin IgG GMCs: 102.8 EL.U/mL (67.1-157.3) compared with 23.4 EL.U/mL (15.1-36.2). CONCLUSION: Vaccines used for infant immunization against Hib and MenC differ in their ability to prime responses to a booster dose of Hib-MenC-TT, and this difference persists to at least 5 years of age. Persistence of antipertussis antibody following a preschool booster of DTaP IPV is also influenced by immunizations received at 2, 3 and 4 months of age, underlining the importance of infant immune priming in the maintenance of antibody levels through childhood. PMID- 22673140 TI - Coronary artery dilation in acute Kawasaki disease and acute illnesses associated with Fever. AB - BACKGROUND: In the absence of a specific test, the diagnosis of clinically incomplete Kawasaki disease (KD) can be challenging. The 2004 American Heart Association guidelines state that the diagnosis of KD is supported by the presence of coronary artery dilation documented by echocardiography. However, the specificity of coronary artery dilation and its prevalence in children with other acute illnesses associated with fever has not been studied. METHODS: A 2-center, prospective study compared the internal diameters and Z-scores (standard deviation [SD] units from the mean internal diameter normalized for body surface area) of the proximal left anterior descending and right coronary arteries measured by echocardiography in febrile children (FC) and children with KD. RESULTS: The median Z-score (interquartile range) of the left anterior descending coronary artery was -0.05 (-0.86, 0.62) and 1.06 (0.36, 2.06) SD units for the 45 FC and the 145 KD patients, respectively (P < 0.0001). For the right coronary artery, the median Z-score was 0.21 (-0.20, 0.87) and 1.04 (0.31, 1.85) SD units for the FC and KD patients, respectively (P < 0.0001). There was no correlation between body temperature at the time of echocardiography and coronary artery Z score. No febrile child had a coronary artery Z-score >= 2.5 SD units. CONCLUSIONS: Z-scores >= 2.5 SD units were not observed in our cohort of FC. Therefore, echocardiographic evidence of coronary artery dilation can be used to support the diagnosis of KD. PMID- 22673141 TI - Recurrent mycotic aneurysm in a 2-year-old boy with group A Streptococcus bacteremia. AB - Mycotic aneurysms represent less than 1% of all reported aneurysms, most of which occur in adults. We present the case of a 2-year-old boy with Streptococcus pyogenes bacteremia and a recurrent mycotic aneurysm. PMID- 22673142 TI - Evolving picture of invasive pneumococcal disease in massachusetts children: a comparison of disease in 2007-2009 with earlier periods. AB - BACKGROUND: As expected, the heptavalent pneumococcal conjugate vaccine (PCV7) had a significant impact on invasive pneumococcal disease (IPD) in children. In addition to the substantial decline in IPD, increased disease due to nonvaccine serotypes and a changing clinical presentation emerged. The objective of this study is to describe these trends in IPD in the late PCV7-era. METHODS: We report on continued, prospective, population-based surveillance of childhood IPD in Massachusetts children during the period 2007 to 2009 and make comparisons with the earlier 2001 to 2006 PCV7-era. Demographic and clinical data were collected for all cases. Streptococcus pneumoniae isolates from normally sterile sites were serotyped and further evaluated using antimicrobial susceptibility testing, multilocus sequence typing and eBURST analysis. IPD incidence rates are calculated by age, year and serotype. RESULTS: There were 326 cases of IPD between 2007 and 2009 in children < 18 years of age. Overall IPD incidence rate was 7.5 cases per 100,000 population and was not statistically different from the observed incidence in 2001 to 2006 (P > 0.05). As compared with the earlier period, the proportion of bacteremic pneumonia among all IPD cases was almost 3 fold greater in 2009 to 2010 (P < 0.01). PCV7 serotypes accounted for 7%, whereas the 13-valent pneumococcal conjugate vaccine serotypes accounted for 77% of all cases between 2007 and 2009. IPD due to serotypes 19A and 7F increased, and 19A and 7F were isolated in 41% and 20% of all IPD cases in the same period, respectively. Serotype 19A also comprised a majority of the penicillin- and ceftriaxone-resistant isolates. Analysis of multilocus sequence typing data showed a significant increase in ST191, ST695 and ST320 and a significant decrease in ST199 and ST180. CONCLUSIONS: The reduction in IPD after introduction of PCV7 persists in Massachusetts children; however, serotypes causing IPD have changed significantly in the last decade. Continued surveillance is necessary to determine the impact of 13-valent pneumococcal conjugate vaccine, as well as track potential changes in disease incidence and character due to non-13-valent pneumococcal conjugate vaccine serotypes. PMID- 22673143 TI - Hemisynthesis and antiproliferative properties of mono-[O-(14-benzoylaconine-8 yl)]esters and bis-[O-(14-benzoylaconine-8-yl)]esters. AB - A series of mono- and bifunctional acyl compounds, build from the 8-O-azeloyl-14 benzoylaconine scaffold and differing by the length of the alkyl linker chain, were synthesised and evaluated against a panel of human tumour cell lines, A-549 (lung cancer), MCF-7 (breast cancer) and HCT-15 (colon cancer). None of the mono [O-(14-benzoylaconine-8-yl)]esters displayed in vitro activity against tumour cells (IC(50) > 60 MUM). However, three bis-[O-(14-benzoylaconine-8-yl)]esters presented a noticeable in vitro cytotoxic activity, those bearing 7, 8 and 9 carbon atoms between the two aconitine moieties, with IC(50)s ranging between 4 and 28 MUM. The most active, bis[O-(14-benzoylaconine-8-yl)]suberate, was then evaluated in vivo in immunodeficient mice bearing human tumour xenografts originating from MCF-7 and HCT-15 cells. For MCF-7 cells, administration of five doses every 4 days, and weekly administration of 4 doses resulted in T/C percent values of 36% (p = 0.001) and 56% (p = 0.02) on day 45, respectively. For HCT-15 cells, administration of five doses every 3 days resulted in 49% tumour regression on the 25th day (p = 0.00001). PMID- 22673144 TI - Synthesis and antimicrobial evaluation of 3-methanone-6-substituted-benzofuran derivatives. AB - Seventeen benzofuran derivatives were synthesized and screened for their antibacterial activities against Escherichia coli, Staphylococcus aureus, Methicillin-resistant S. aureus, Bacillus subtilis, and Pseudomonas aeruginosa. Seven of them have showed excellent antibacterial activities compared to the positive controls (Cefotaxime and Sodium Penicillin). The substitutions at C-6 and C-3 positions of these derivatives were found to greatly impact on the antibacterial activity and strains specificity, respectively. Specifically, compounds bearing a hydroxyl group at C-6 (5a, 5b, 5c and 12) offered excellent antibacterial activities against all five above-mentioned strains (MIC(80) = 0.78 12.5 ug/mL), and those with imine (15) and (3, 4, 5-trimethoxyphenyl) methanone (7e), respectively, at C-3 position showed selective activity against S. aureus among five tested strains with great MIC(80) values (3.12-12.5 ug/mL). PMID- 22673145 TI - Does maltreatment beget maltreatment? A systematic review of the intergenerational literature. AB - In this article, the authors critically review the literature testing the cycle of maltreatment hypothesis which posits continuity in maltreatment across adjacent generations. That is, the authors examine whether a history of maltreatment victimization is a significant risk factor for the later perpetration of maltreatment. The authors begin by establishing 11 methodological criteria that studies testing this hypothesis should meet. They include such basic standards as using representative samples, valid and reliable measures, prospective designs, and different reporters for each generation. The authors identify 47 studies that investigated this issue and then evaluate them with regard to the 11 methodological criteria. Overall, most of these studies report findings consistent with the cycle of maltreatment hypothesis. Unfortunately, at the same time, few of them satisfy the basic methodological criteria that the authors established; indeed, even the stronger studies in this area only meet about half of them. Moreover, the methodologically stronger studies present mixed support for the hypothesis. As a result, the positive association often reported in the literature appears to be based largely on the methodologically weaker designs. Based on this systematic methodological review, the authors conclude that this small and methodologically weak body of literature does not provide a definitive test of the cycle of maltreatment hypothesis. The authors conclude that it is imperative to develop more robust and methodologically adequate assessments of this hypothesis to more accurately inform the development of prevention and treatment programs. PMID- 22673146 TI - Outside fibroblasts play a key role in the development of inner neointima after the implantation of polytetrafluoroethylene grafts. AB - The neointima formation inside of polytetrafluoroethylene (PTFE) grafts may be associated with the migration of outside fibroblasts to the luminal surfaces. This study aimed to verify whether blockade of fibroblast migration can prevent neointima formation by testing two types of prosthetic vessels, the porous PTFE graft and the impermeable Grasil graft, respectively. After implantation of the PTFE graft in dogs, a time-dependent migration of outside fibroblasts to the luminal side occurred. Compared with the PTFE grafts, the total neointima formation in the Grasil grafts was significantly less. Although the neointima formation at the arterial or venous anastomotic regions did not significantly differ between the two grafts, the neointima at the middle region of the PTFE grafts was significantly evident than the Grasil grafts. The components of the renin-angiotensin system (RAS), such as angiotensin II and its receptor AT1, as well as the forming enzymes of the RAS (angiotensin-converting enzyme and chymase), were all detectable in the grafts' surrounding tissues. Neointima formation at the middle region of the prosthetic vessels could be suppressed almost completely by the blockade of outside fibroblast migration, indicating that outside fibroblasts play a key role in the formation of neointima in this region. PMID- 22673148 TI - Add-on aliskiren elicits stronger renoprotection than high-dose valsartan in type 2 diabetic KKAy mice that do not respond to low-dose valsartan. AB - We hypothesized that aliskiren provides renoprotection in diabetic animals that did not receive sufficient renoprotection by AT1-receptor antagonist treatment. Type 2 diabetic KKAy mice were treated with group 1: vehicle or group 2: valsartan (15 mg/kg per day) from 12 to 16 weeks of age. The mice were subsequently divided into 4 groups and treated with the following combinations of drugs for another 6 weeks: 1: group 1 kept receiving vehicle, 2: group 2 continuously received 15 mg/kg per day of valsartan (Val-Val15), 3: group 2 received 50 mg/kg per day of valsartan (Val-Val50), 4: group 2 continuously received 15 mg/kg per day of valsartan with 25 mg/kg per day of aliskiren (Val Val+Ali). Aliskiren exerted significant anti-albuminuric effects, whereas valsartan failed to ameliorate the albuminuria in the first four weeks. Surprisingly, the increasing dosage of valsartan in the Val-Val50 group showed non-significant tendencies to attenuate the albuminuria compared with vehicle infusion. Val-Val+Ali significantly suppressed the development of albuminuria and podocyte injury. Val-Val50 and Val-Val+Ali showed similar suppression of angiotensin II contents in the kidney of KKAy mice. In conclusion, the anti albuminuric effect that was observed in the type 2 diabetic mice showing no anti albuminuric effect by valsartan can be attributed to the add-on aliskiren. PMID- 22673147 TI - Renal protection of in vivo administration of tempol in streptozotocin-induced diabetic rats. AB - The present study was carried out to investigate the protective effects of tempol on renal function and the underlying mechanism in streptozotocin-induced diabetic rats. The diabetic rats were randomly divided into the model group (without tempol) and tempol group (1 mM tempol in drinking water for 6 weeks). Nondiabetic rats were served as the Control group. The mRNA expression of canonical transient receptor potential 6 (TRPC6), transforming growth factor (TGF)-beta1, and type IV collagen (Col IV) were examined. The malondialdehyde (MDA) level, activities of superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in renal tissues were measured to assess redox status in kidneys. We found that tempol significantly reduced 24-h urine output and urine albuminuria excretion in the diabetic rats. Compared with the model group, the concentration of MDA was significantly lower in the tempol group. In addition, diabetes decreased activities of SOD and GSH-Px and these responses were prevented by tempol treatment. Moreover, in diabetic rats, the mRNA expression levels of TGF-beta1 and Col IV were upregulated. TRPC6 mRNA expression level was down-regulated in diabetic kidneys. However, all of these diabetic effects were significantly suppressed by tempol treatment. These results suggest that chronic treatment of diabetic rats with tempol can protect kidneys, possibly by reducing expression of TGF-beta1, Col IV, and upregulating TRPC6 expression level. PMID- 22673149 TI - Application of NMR-based metabonomics suggests a relationship between betaine absorption and elevated creatine plasma concentrations in catheterised sows. AB - The objective of the present explorative study was to determine the absorption dynamics when feeding diets varying in types and levels of dietary fibre in a catheterised animal model. A total of six sows were fed a diet low in fibre (LF), a diet high in soluble fibre and a diet high in insoluble fibre in a repeated 3 * 3 cross-over design. Plasma samples were collected from the mesenteric artery and the portal vein to determine different absorption phases by 1H NMR spectroscopy based metabonomics. Time profiles were determined for plasma levels of specific metabolites and for the absorption of these metabolites from the small intestine. The LF diet resulted in a higher betaine concentration in the blood than the two high-fibre diets (P=0.008). This leads to higher plasma concentrations of methionine (P=0.0028) and creatine (P=0.020) of endogenous origin. In conclusion, the use of NMR spectroscopy for measuring nutrient uptake in the present study elucidated the relationship between betaine uptake and elevated creatine plasma concentrations. PMID- 22673151 TI - Epigenetics. Going places with BANCR. AB - A screen for transcripts affected by the expression of the oncogene BRAFV600E has identified a long noncoding RNA as being crucial for melanoma cell migration. PMID- 22673150 TI - Managing drug resistance in cancer: lessons from HIV therapy. AB - Drug resistance is a common cause of treatment failure for HIV infection and cancer. The high mutation rate of HIV leads to genetic heterogeneity among viral populations and provides the seed from which drug-resistant clones emerge in response to therapy. Similarly, most cancers are characterized by extensive genetic, epigenetic, transcriptional and cellular diversity, and drug-resistant cancer cells outgrow their non-resistant peers in a process of somatic evolution. Patient-specific combination of antiviral drugs has emerged as a powerful approach for treating drug-resistant HIV infection, using genotype-based predictions to identify the best matched combination therapy among several hundred possible combinations of HIV drugs. In this Opinion article, we argue that HIV therapy provides a 'blueprint' for designing and validating patient specific combination therapies in cancer. PMID- 22673152 TI - Epigenetics. Dissecting driving DNA methylations. AB - A new study identifies cancer-specific DNA-methylated genes the continued repression of which may be required for cell survival. PMID- 22673153 TI - Spotlight on the role of COP1 in tumorigenesis. AB - COP1 is an E3 ubiquitin ligase that is involved in the ubiquitylation of various protein substrates to trigger their proteasomal degradation. Although originally identified in a light signalling pathway in plants, biochemical studies have identified putative targets of mammalian COP1 with relevant roles in tumorigenesis, including the oncoproteins JUN and ETV family members, as well as the p53 tumour suppressor. Recent genetic studies have shown that COP1 deficiency leads to spontaneous tumour formation in mice, and have identified mutations in COP1 and its substrates in various human cancers. These findings add to our growing appreciation of the roles for E3 ligases in cancer. PMID- 22673154 TI - Treatment seeking and subsequent 1-year drinking outcomes among treatment clients in Sweden and the U.S.A.: a cross-cultural comparison. AB - Cross-cultural comparisons provide a method for distinguishing unique aspects as well as shared aspects of different cultures. Theoretically framed by a health services conceptual model, we examine the extent that culture-specific versus common characteristics are associated with treatment seeking and drinking outcome. Swedish (n=997) and U.S. (n=501) alcohol-dependent individuals were interviewed at baseline and 1-year (n=635 and n=384 respectively). Both studies gathered comparable background, help-seeking, and drinking data. Regression models tested predictors of 1-year follow-up drinking defined as abstinence or moderate drinking versus heavy drinking. Swedish individuals were older and had social networks comprised mostly of substance abusers compared to U.S. individuals who reported higher problem severity and greater drug involvement. Whereas U.S. individuals reported greater prior mutual-help attendance, Swedish individuals reported greater prior treatment involvement. Better 1-year drinking outcomes were reported by women, younger age groups and those with an abstinence goal in both samples. Cultural and institutional differences were apparent. For example, with Swedish individuals having a mostly non-using network predicted better outcomes, whereas lower problem severity was a predictor for U.S. individuals. PMID- 22673155 TI - Adolescent nicotine dependence symptom profiles and risk for future daily smoking. AB - Recent research on adolescent smokers suggests that there are important differences in the types of nicotine dependence (ND) symptoms that emerge and different patterns of ND symptoms. The purpose of this study was to use data from the longitudinal Social and Emotional Contexts of Adolescent Smoking Patterns Study to identify latent subgroups of adolescent experimental and nondaily smokers varying in number and types of endorsed ND symptoms. Profiles were identified using baseline level of smoking, individual patterns of ND symptoms and other ND risk factors. Discrete time survival analysis was used to examine profile differences in probability of becoming daily smokers 48 months later. Four distinct subgroups of smokers with different patterns of smoking behavior, ND symptoms, and alcohol and other substance use emerged. Heavier smoking adolescents with high symptom endorsement, particularly the need to smoke in the morning, were most likely to become daily smokers 48 months later. A subgroup of social smokers had high smoking exposure and symptom endorsement (except need to smoke in the morning), and high levels of other substance use. Despite lower rates of smoking frequency and quantity compared to the heavier smoking class, 36% of these adolescents smoked daily by 48 months, with a steeper decline in survival rates compared to other lighter smoking classes. Morning smoking symptoms and symptoms prioritizing smoking (i.e., choosing to spend money on cigarettes instead of lunch or smoking when ill or where smoking is forbidden) might quickly identify adolescent non-daily smokers with more severe dependence and higher risk for daily smoking. A focus on skills for avoiding social situations involving use of alcohol and other drugs and reducing peer smoking influences may be an important focus for reducing smoking and other substance use among social smokers. PMID- 22673156 TI - Crystallographic studies of heme oxygenase complexed with an unstable reaction intermediate, verdoheme. AB - This article discusses the accuracy of X-ray structural studies of heme oxygenase (HO) in complex with an unstable intermediate, verdoheme. Heme degradation by HO proceeds through three successive steps of O(2) activation. The mechanism of the third step, the ring opening of verdoheme, has been the least understood. Recent structural studies of the verdoheme-HO complex provide detailed information concerning this mechanism. Due to X-ray-induced photoreduction and the instability of verdoheme, it has been difficult to obtain an accurate structure for the ferrous verdoheme-HO complex. Therefore, accurate structural studies, including analysis of the electronic state of the verdoheme-HO complex, are needed to elucidate the proper reaction mechanism. PMID- 22673157 TI - A dimerized urea-based inhibitor of the prostate-specific membrane antigen for 68Ga-PET imaging of prostate cancer. AB - BACKGROUND: Alternative positron-emission tomography (PET) probes like labeled inhibitors of the prostate-specific membrane antigen (PSMA) are of emerging clinical impact as they show the ability to image small lesions of recurrent prostate cancer. Here, the dimerization of the pharmacophore Glu-ureido-Lys via the 68Ga chelator N,N'-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N' diacetic acid (HBED-CC) was investigated to further improve the binding characteristics and pharmacokinetics. METHODS: The peptidomimetic structures were synthesized by solid-phase chemistry, and the resulting products were coupled with the respective 2,3,5,6-tetrafluorophenol esters of HBED-CC to form the monomeric reference and the dimeric Glu-ureido-Lys derivative. The binding properties were analyzed in competitive binding, internalization, and cell surface retention experiments. PET images and biodistribution data were obtained 1 h after injection in BALB/c nu/nu mice bearing LNCaP tumor xenografts. RESULTS: Cell binding data revealed significant better binding properties of the dimer (IC50 = 3.9 +/- 1.8 nM; IC50 (monomer) = 12.1 +/- 2.1 nM). The inhibition potency investigated by the enzyme-based NAALADase assay confirmed these results. Specific internalization in LNCaP cells was demonstrated for both, the monomer and dimer. As shown by efflux measurements, the dimeric compound was more effectively retained on the cell surface, resulting in advanced in vivo properties (T/BMonomer = 9.2; T/BDimer = 26.5). CONCLUSIONS: The dimeric [68Ga]7 is a promising imaging agent for PSMA-expressing tumors as it shows higher tumor uptake while observing more favorable background clearance. As compared to the respective monomer, the higher affinity and prolonged tumor retention additionally represent promising features and warrant further evaluation regarding 68Ga-PET imaging of PSMA expression. PMID- 22673158 TI - Building life-long learning capacity in undergraduate nursing freshmen within an integrative and small group learning context. AB - BACKGROUND: Life-long learning involves the development of skills in critical thinking (CT), effective group process (GP), and self-directedness (SDL). Recent studies have shown that small group learning with active interactions is effective in enabling students to develop themselves as independent learners beyond graduation. With a view to integrative learning, the purpose of this study was to evaluate life-long learning outcomes through the work of small group teaching and learning for a class of undergraduate nursing freshmen during one academic year. METHODS: A mixed-methods approach was used to evaluate the CT, GP and SDL of 99 freshmen with a self-assessment questionnaire before and after their learning activities in three nursing courses, and to identify themes from a total of six focus group interviews with the students and teachers. RESULTS: The CT, GP and SDL results obtained from self-assessment did not indicate significant differences. Four themes emerged from the qualitative analysis. DISCUSSION: Many factors contributed to the results on life-long learning skill development of students in this study. The qualitative analysis provided good insights for future teaching and learning development. CONCLUSIONS: With a developmental perspective, life-long learning may be better developed and evaluated over a longer period of time in the nursing program. PMID- 22673159 TI - The effectiveness of video-assisted debriefing versus oral debriefing alone at improving neonatal resuscitation performance: a randomized trial. AB - INTRODUCTION: Debriefing is a critical component of effective simulation-based medical education. The optimal format in which to conduct debriefing is unknown. The use of video review has been promoted as a means of enhancing debriefing, and video-assisted debriefing is widely used in simulation training. Few empirical studies have evaluated the impact of video-assisted debriefing, and the results of those studies have been mixed. The objective of this study was to compare the effectiveness of video-assisted debriefing to oral debriefing alone at improving performance in neonatal resuscitation. METHODS: Thirty residents, divided into 15 teams of 2 members each, participated in the study. Each team completed a series of 3 neonatal resuscitation simulations. Each simulation was followed by a facilitated debriefing. Teams were randomly assigned to receive either oral debriefing alone or video-assisted debriefing after each simulation. Objective measures of performance and times to complete critical tasks in resuscitation were evaluated by blinded video review on the first (pretest) and the third (posttest) simulations using a previously validated tool. RESULTS: Overall neonatal resuscitation performance scores improved in both groups [mean (SD), 83% (14%) for oral pretest vs. 91% (7%) for oral posttest (P = 0.005); 81% (16%) for video pretest vs. 93% (10%) for video posttest (P < 0.001)]. There was no difference in performance scores between the 2 groups on either the pretest or posttest [overall posttest scores, 91.3% for oral vs. 93.4% for video (P = 0.59)]. Times to complete the critical tasks of resuscitation also did not differ significantly between the 2 study groups. The educational effect of the video assisted debriefing versus oral debriefing alone was small (d = 0.08). CONCLUSIONS: Using this study design, we failed to show a significant educational benefit of video-assisted debriefing. Although our results suggest that the use of video-assisted debriefing may not offer significant advantage over oral debriefing alone, exactly why this is the case remains obscure. Further research is needed to define the optimal role of video review during simulation debriefing in neonatal resuscitation. PMID- 22673160 TI - Post transcriptional regulation: Chimeric protein production. PMID- 22673161 TI - Genome evolution: Functional antagonism and human brain evolution. PMID- 22673162 TI - Complex traits: Predicting phenotypes. PMID- 22673163 TI - Activated O2(*-) and H2O2 mediated cell survival in SU11274-treated non-small cell lung cancer A549 cells via c-Met-PI3K-Akt and c-Met-Grb2/SOS-Ras-p38 pathways. AB - The pharmacological activity of SU11274 is primarily due to its inhibition of hepotocyte growth factor receptor (c-Met) kinase overexpression. In this study, we demonstrated that the pathway involved in SU11274-induced autophagy was presumably through inhibition of c-Met and its down-stream pathways, including phosphatidylinositol 3-kinases - Akt (PI3K-Akt) and the growth factor receptor bound protein-2 / son of sevenless - Ras - p38 MAPK (Grb2/SOS-Ras-p38) pathway. SU11274 time-dependently induced the generation of superoxide anion (O2(*-)) and hydrogen peroxide (H2O2). There is a negative feedback loop between reactive oxygen species (ROS) induction and SU11274. Then, we investigated the role of ROS in protecting cells against SU11274-induced autophagic cell death in A549 cells. O2(*-) and H2O2 generation activated c-Met-PI3K-Akt and c-Met-Grb2/SOS-Ras-p38 signaling pathways, which were suppressed by O2(*-) scavenger superoxide dismutase (SOD) and H2O2 scavenger catalase. In conclusion, O2(*-) and H2O2 evoked cell resistance to SU11274 via activating c-Met-PI3K-Akt and c-Met Grb2/SOS-Ras-p38 pathways in A549 cells. SU11274 also induced ROS generation in Caenorhabditis elegans. PMID- 22673164 TI - Pregnancy gingivitis and pregnancy tumour. PMID- 22673165 TI - The demise of Assisted Human Reproduction Canada. PMID- 22673166 TI - Elective caesarean section for the mature nullipara? PMID- 22673167 TI - Little congruence between health care provider and patient perceptions of counselling on gestational weight gain. AB - OBJECTIVE: To determine the self-reported counselling practices of health care providers with regard to prenatal weight gain and the risks of inappropriate gain. METHODS: We conducted a cross-sectional survey using a self-administered questionnaire at obstetrician, midwifery, and family medicine clinics in Hamilton, Ontario. Health care providers were eligible to participate if they provided prenatal care and could read English sufficiently well to complete the survey. RESULTS: Forty-two health care providers completed the survey; of these, 95% reported counselling women to gain a specific amount of weight, and 81% reported that they recommended values that were in accordance with the 2009 Institute of Medicine/Health Canada guidelines. The risks of excess and inadequate gain were reported as being discussed with their patients by 87% and 76% of health care providers, respectively. CONCLUSION: In this first study to the best of our knowledge of gestational weight gain counselling since the publication of the 2009 guidelines, most health care providers reported discussing weight gain and the risks of inappropriate gain, which is incongruent with previously published information on their patients' reports of counselling. PMID- 22673168 TI - Early versus delayed cord clamping in term and preterm births: a review. AB - The optimal timing for cord clamping, early versus delayed, in the third stage of labour is a controversial subject. Issues surrounding the timing of cord clamping include gestational age and maternal and neonatal considerations. Delayed cord clamping (DCC) has been shown to increase placental transfusion, leading to an increase in neonatal blood volume at birth of approximately 30%. In the term infant, although this may result in an increase in iron stores, thereby decreasing the risk of anemia, it may adversely increase the risk of jaundice and the need for phototherapy. In the preterm infant, DCC (or even milking of the cord) decreases the need for blood transfusions for anemia, the number of such transfusions, and the risks of intraventricular hemorrhage and late-onset sepsis. Advantages of DCC also include a reduction in alloimmunization in Rh-negative women, although this advantage is theoretical and unproven. We searched multiple databases including PubMed Clinical Queries, Trip Database, Cochrane Systematic Reviews, and UpToDate, as well as published guidelines from the Society of Obstetricians and Gynaecologists of Canada, the American Congress of Obstetricians and Gynecologists, and the Royal College of Obstetricians and Gynaecologists. We preferentially selected systematic reviews and randomized controlled trials for this literature review. Overall, the available evidence appears to suggest that DCC is likely to result in better neonatal outcomes in both term and preterm infants, even in areas where neonatal iron deficiency anemia is rare. However, there is insufficient evidence to date to support a recommendation to delay cord clamping in non-vigorous infants requiring resuscitation. PMID- 22673169 TI - A review of therapeutic abortions and related areas of concern in Canada. AB - OBJECTIVE: To review the legal status of abortion and its prevalence, safety, and accessibility in Canada and to highlight related areas of concern. METHODS: We conducted a review of research literature, published reports, websites, and articles in order to describe abortion services and associated issues such as access, availability, and safety in Canada. RESULTS: Therapeutic abortion is often the result of unintended pregnancy. Even so, emergency contraception may not be accessible for all Canadian women, and effective contraception is underutilized. In Canada, abortion has been decriminalized and is generally safe, but current reports of prevalence and complication rates are inconsistent. Abortion rates appear to be decreasing. Medical or surgical termination of pregnancy is available and often publicly funded. However, barriers related to time, cost, travel, and regional disparities hamper unrestricted access to therapeutic abortion in this country, and although the place of abortion in medical education remains controversial, current curriculum content appears to be inadequate. CONCLUSIONS: The Society of Obstetricians and Gynaecologists of Canada states that comprehensive family planning services, including therapeutic abortion, should be freely available to all. The Canadian Medical Association affirms that induced abortion should be uniformly available to all women. In Canada, the issues related to therapeutic abortion access, availability, and safety must be addressed. PMID- 22673170 TI - Pain and psychological characteristics in women waiting for gynaecological surgery. AB - OBJECTIVE: Pain is frequently a complaint prior to gynaecological surgery. Psychological factors are also known to influence the experience of pain. The primary objective of this study was to assess the prevalence of pain and the relationship between psychological factors and pain in women awaiting gynaecological surgery. METHODS: Four hundred twenty-nine women in a tertiary care centre in southeastern Ontario were included in this cross-sectional analysis, which was embedded in a larger prospective study. Pain was assessed using the Brief Pain Inventory, anxiety using the State Trait Anxiety Inventory, depressive symptoms using the Center for Epidemiologic Studies Depression Scale, somatization using the Seven Symptom Screening Test, and catastrophizing with an abbreviated coping strategies questionnaire. RESULTS: Eighteen percent of women reported high anxiety, 37% reported depressive symptoms, 47% had two or more symptoms of somatization, and 40% reported elevated pain catastrophizing. Approximately one third reported moderate to severe pain intensity and interference. Of those reporting pain, 81% believed their pain was due to their primary condition. Depressive symptoms, somatization, and catastrophizing were associated with elevated pain intensity and interference. CONCLUSION: The responses suggest a substantial burden of pain, anxiety, and depressive symptoms in women awaiting gynaecological surgery. Further research is needed to assess the management of these symptoms and their impact on health care resources and the well-being of women in this setting. PMID- 22673171 TI - Clinical predictors of endometriosis in the infertility population: is there a better way to determine who needs a laparoscopy? AB - OBJECTIVE: Endometriosis is a known contributor to infertility, but the gold standard for its diagnosis is surgical. Therefore, it is important for clinicians to be able to predict which women with infertility are at high risk for endometriosis and thus should be offered laparoscopy. We sought to identify the clinical predictors of endometriosis in the infertility population. METHODS: We conducted a retrospective review of patients at an academic infertility centre. The primary outcome was identification of endometriosis at laparoscopy, and we used logistic regression to test clinical variables for their ability to predict endometriosis. RESULTS: Primary infertility, dysmenorrhea, and uterosacral/cul-de sac nodularity were significant independent predictors of finding endometriosis at laparoscopy. Other clinical variables (including hysterosalpingogram findings) were not independent predictors of endometriosis, and physicians with an endometriosis-focused practice were more likely to diagnose endometriosis at laparoscopy. CONCLUSION: Key predictors of endometriosis in the infertility population are primary infertility, dysmenorrhea, and uterosacral/cul-de-sac nodularity. These results will be used to develop and validate a formal clinical prediction model for endometriosis in infertile women. PMID- 22673172 TI - Optimal debulking targets in women with advanced stage ovarian cancer: a retrospective study of immediate versus interval debulking surgery. AB - OBJECTIVE: The objective of this study was to examine both overall and disease free survival of patients with advanced stage ovarian cancer after immediate or interval debulking surgery based on residual disease. METHODS: We performed a retrospective chart review at the Tom Baker Cancer Centre in Calgary, Alberta of patients with pathologically confirmed stage III or IV ovarian cancer, fallopian tube cancer, or primary peritoneal cancer between 2003 and 2007. We collected data on the dates of diagnosis, recurrence, and death; cancer stage and grade, patients' age, surgery performed, and residual disease. RESULTS: One hundred ninety-two patients were included in the final analysis. The optimal debulking rate with immediate surgery was 64.8%, and with interval surgery it was 85.9%. There were improved overall and disease-free survival rates for optimally debulked disease (< 1 cm) with both immediate and interval surgery (P < 0.001) compared to suboptimally debulked disease. Overall survival rates for optimally debulked disease were not significantly different in patients having immediate and interval surgery (P = 0.25). In the immediate surgery group, patients with microscopic residual disease had better disease-free survival (P = 0.015) and overall survival (P = 0.005) than patients with < 1 cm residual disease. In patients who had interval surgery, those who had microscopic residual disease had more improved disease-free survival than those with < 1 cm disease (P = 0.05), but they did not have more improved overall survival (P = 0.42). Patients with microscopic residual disease who had immediate surgery had a significantly better overall survival rate than those who had interval surgery (P = 0.034). CONCLUSION: In women with advanced stage ovarian cancer, the goal of surgery should be resection of disease to microscopic residual at the initial procedure. This results in improved overall survival than lesser degrees of resection. Further studies are required to determine optimal surgical management. PMID- 22673174 TI - Canadian HIV pregnancy planning guidelines. AB - OBJECTIVE: Four main clinical issues need to be considered for HIV-positive individuals and couples with respect to pregnancy planning and counselling: (1) pre-conceptional health; (2) transmission from mother to infant, which has been significantly reduced by combined antiretroviral therapy; (3) transmission between partners during conception, which requires different prevention and treatment strategies depending on the status and needs of those involved; and (4) management of infertility issues. The objective of the Canadian HIV Pregnancy Planning Guidelines is to provide clinical information and recommendations for health care providers to assist HIV-positive individuals and couples with their fertility and pregnancy planning decisions. These guidelines are evidence- and community-based and flexible, and they take into account diverse and intersecting local/population needs and the social determinants of health. OUTCOMES: Intended outcomes are (1) reduction of risk of vertical transmission and horizontal transmission of HIV, (2) improvement of maternal and infant health outcomes in the presence of HIV, (3) reduction of the stigma associated with pregnancy and HIV, and (4) increased access to pregnancy planning and fertility services. EVIDENCE: PubMed and Medline were searched for articles published in English or French to December 20, 2010, using the following terms: "HIV" and "pregnancy" or "pregnancy planning" or "fertility" or "reproduction" or "infertility" or "parenthood" or "insemination" or "artificial insemination" or "sperm washing" or "IVF" or "ICSI" or "IUI." Other search terms included "HIV" and "horizontal transmission" or "sexual transmission" or "serodiscordant." The following conference databases were also searched: Conference on Retroviruses and Opportunistic Infections, International AIDS Conference, International AIDS Society, Interscience Conference on Antimicrobial Agents and Chemotherapy, the Canadian Association of HIV/AIDS Research, and the Ontario HIV Treatment Network Research Conference. Finally, a hand search of key journals and conferences was performed, and references of retrieved articles were reviewed for additional citations. Subsequently, abstracts were categorized according to their primary topic (based on an outline of the guidelines) into table format with the following headings: author, title, study purpose, participants, results and general comments. Finally, experts in the field were consulted for their opinions as to whether any articles were missed. VALUES: The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. Recommendations for practice were ranked according to the method described in that report (Table) and through use of the Appraisal of Guidelines Research and Evaluation instrument for the development of clinical guidelines. SPONSORS: The Society of Obstetricians and Gynaecologists of Canada, Women and HIV Research Program, Women's College Research Institute, Women's College Hospital, University of Toronto, Abbott Laboratories Canada, the Ontario HIV Treatment Network, the Canadian Institutes of Health Research, and the Canadian HIV Trials Network. KEY POINTS AND RECOMMENDATIONS: HIV-positive people who are considering pregnancy should be counselled on the following issues so they can make an informed decision. PMID- 22673173 TI - Combination of serum biomarkers to differentiate malignant from benign ovarian tumours. AB - OBJECTIVE: To investigate biomarkers and clinical parameters to distinguish ovarian cancers from benign ovarian tumours. METHODS: Serum biomarkers (CA 125, human epididymis protein 4 [HE 4], interleukin-18 [IL-18], leptin, macrophage migration inhibitory factor [MIF], fibroblast growth factor 2 [FGF-2], insulin like growth factor, osteopontin, prolactin) and the risk of malignancy indexes I and II (RMI-I and RMI-II) scores were obtained prior to surgery in 52 patients with ovarian tumours (37 malignant and 15 benign). ROC curves were built for each individual marker, for logistic regression models using all markers, and for models combining both biomarkers and RMI scores. RESULTS: The model with nine biomarkers performed well (specificity 93%, sensitivity 84%) and was more reliable than the RMI-I or RMI-II alone. A regression model combining RMI-II and six of the biomarkers (CA 125, HE 4, IL-18, leptin, MIF, and FGF-2) allowed differentiation between the cancer and non-cancer cases in this pilot study. CONCLUSION: The regression models using biomarkers combined with clinical scoring systems warrant further investigation to improve triage of patients with ovarian tumours to enhance utilization of resources and optimize patient care. PMID- 22673175 TI - Eggshell thinning and decreased concentrations of vitamin E are associated with contaminants in eggs of ivory gulls. AB - The ivory gull is a high Arctic seabird species threatened by climate change and contaminant exposure. High levels of contaminants have been reported in ivory gull Pagophila eburnea eggs from Svalbard and the Russian Arctic. The present study investigated associations between high levels of contaminants (organochlorinated pesticides (OCPs), polychlorinated biphenyls (PCBs), brominated flame retardants (BFRs), perfluorinated alkyl substances (PFASs) and mercury (Hg)) and three response variables: eggshell thickness, retinol (vitamin A) and alpha-tocopherol (vitamin E). Negative associations were found between levels of OCPs, PCBs and BFRs and eggshell thickness (p<0.021) and alpha tocopherol (p<0.023), but not with retinol (p>0.1). There were no associations between PFASs and mercury and the three response variables. Furthermore, the eggshell thickness was 7-17% thinner in the present study than in archived ivory gull eggs (<=1930). In general, a thinning above 16 to 20% has been associated with a decline in bird populations, suggesting that contaminant-induced eggshell thinning may constitute a serious threat to ivory gull populations globally. PMID- 22673176 TI - Controls on soil solution nitrogen along an altitudinal gradient in the Scottish uplands. AB - Nitrogen (N) deposition continues to threaten upland ecosystems, contributing to acidification, eutrophication and biodiversity loss. We present results from a monitoring study aimed at investigating the fate of this deposited N within a pristine catchment in the Cairngorm Mountains (Scotland). Six sites were established along an elevation gradient (486-908 m) spanning the key habitats of temperate maritime uplands. Bulk deposition chemistry, soil carbon content, soil solution chemistry, soil temperature and soil moisture content were monitored over a 5 year period. Results were used to assess spatial variability in soil solution N and to investigate the factors and processes driving this variability. Highest soil solution inorganic N concentrations were found in the alpine soils at the top of the hillslope. Soil carbon stock, soil solution dissolved organic carbon (DOC) and factors representing site hydrology were the best predictors of NO(3)(-) concentration, with highest concentrations at low productivity sites with low DOC and freely-draining soils. These factors act as proxies for changing net biological uptake and soil/water contact time, and therefore support the hypothesis that spatial variations in soil solution NO(3)(-) are controlled by habitat N retention capacity. Soil percent carbon was a better predictor of soil solution inorganic N concentration than mass of soil carbon. NH(4)(+) was less affected by soil hydrology than NO(3)(-) and showed the effects of net mineralization inputs, particularly at Racomitrium heath and peaty sites. Soil solution dissolved organic N concentration was strongly related to both DOC and temperature, with a stronger temperature effect at more productive sites. Due to the spatial heterogeneity in N leaching potential, a fine-scale approach to assessing surface water vulnerability to N leaching is recommended over the broad scale, critical loads approach currently in use, particularly for sensitive areas. PMID- 22673177 TI - Optimal management of the flood risks of floodplain development. AB - This paper presents a model of the problem on floodplain development, exploring the conditions that are both necessary and sufficient for development to be optimal. The model is calibrated for a particular catchment, the Ouse catchment in the United Kingdom, and is used both to estimate the expected impact of floodplain development and to explore the impact of alternative policy instruments. We find that the use of price-based instruments that signal the expected flood damage cost of floodplain development has the potential to lead to outcomes close to the social optimum. The finding is robust to two types of uncertainty: model error about the relation between precipitation and flood-risk and measurement error about the benefits of developed floodplains. PMID- 22673178 TI - The effects of skeletal separation and moisture enhancement for improving the eating quality of cull cow beef. AB - Sixty-two cull beef cows were slaughtered to investigate effects of skeletal separation and moisture enhancement on beef eating quality. Muscles from each carcass side were randomly assigned to 1) no postmortem processing (NPP), 2) prerigor skeletal separation (SS), 3) moisture enhancement (ME) using calcium ascorbate or 4) a combination of SS and ME (SS/ME). Postmortem processing treatment (PPT) by ageing (PM) interactions (P<0.01) for shear force were present for longissimus. As PM ageing increased from 7 to 21 d, there was a greater decrease (P<0.05) in shear force with NPP vs. all other PPT. Trained taste panellists found SS, ME and SS/ME improved (P<0.05) palatability attributes vs. NPP. An additive effect of combining SS and ME improved palatability traits versus SS or ME alone. Panellists found no differences (P>0.14) in softness and tenderness between SS/ME and Canadian AA or AAA beef. Postmortem processing of beef cows may produce beef as tender and juicy as beef from younger carcasses. PMID- 22673179 TI - Addition of seaweed (Laminaria digitata) extracts containing laminarin and fucoidan to porcine diets: influence on the quality and shelf-life of fresh pork. AB - A seaweed extract containing laminarin (L) and fucoidan (F) (L/F) was manufactured from brown seaweed (Laminaria digitata) in spray-dried (L/F-SD) and wet (L/F-WS) forms. The effect of supplementation of pig diets with L/F-SD and L/F-WS (L, 500 mg/kg feed; F, 420 mg/kg feed) for 21 days pre-slaughter, on quality indices of fresh M. longissimus dorsi (LD) steaks was examined. Susceptibility of porcine liver, heart, kidney and lung tissue homogenates to iron-induced (1mM FeSO4) lipid oxidation was also investigated. Dietary supplementation with L/F did not increase plasma total antioxidant status (TAS). In LD steaks stored in modified atmosphere packs (80% O2:20% CO2) (MAP) for up to 15 days at 4 degrees C, muscle pH, surface colour (CIE 'L*' lightness, 'a*' redness and 'b*' yellowness values) and microbiology (psychrotrophic and mesophilic counts, log CFU/g pork) were unaffected by dietary L/F. In general, levels of lipid oxidation (TBARS, mg MDA (malondialdehyde)/kg pork) followed the order: C>LF-SD>L/F-WS. A statistically significant reduction in lipid oxidation (P<0.05) was observed in LD steaks from 75% of pigs (n=6) fed with L/F-WS compared to controls. Iron-induced lipid oxidation increased in liver, heart, kidney and lung tissue homogenates over the 24h storage period and dietary L/F-WS reduced lipid oxidation to the greatest extent in liver tissue homogenates. Results demonstrate potential for the incorporation of marine-derived bioactive antioxidant components into muscle foods via the animal's diet. PMID- 22673180 TI - Endothelial function and other biomarkers of cardiovascular risk in frequent consumers of street food. AB - BACKGROUND & AIMS: Street food (SF) is defined as out-of-home food consumption, and generally consists of energy dense meals rich in saturated fats, and poor in fibers, vitamins and anti-oxidants. Though SF consumption may have unfavorable metabolic and cardiovascular effects, its possible association with endothelial function has not been considered. METHODS: Participants were recruited among those who took part in a previous study of ours, done in Palermo, Italy, which investigated the association between consumption of SF and health in 1002 people. In that study, a score of SF consumption was obtained by categorizing each of ten foods consumed less than or more than once a month (0 = never consumed, 1 = once a month or less, 2 = more than once a month; thus, the sum of single scores could range from 0 to 20). Based on the interquartile values of SF score distribution, in the present study we included low SF consumers, defined on the basis of the first interquartile SF score range (range: 0-1), and high SF consumers, who were those in the forth interquartile range of the SF score (range: 7-20). The group of low SF consumers had 12 participants (median value of SF score: 1; range: 0 1), that of high SF consumers had 13 (median value of SF score: 11; range: 10 16). The brachial artery flow-mediated dilatation (FMD), a measure of endothelial function, and other cardiovascular biomarkers were investigated. RESULTS: High SF consumers had higher BMI (P = 0.026), larger waist circumference (P = 0.041), higher levels of cholesterol (P = 0.013) and uric acid serum concentrations (P = 0.002) compared with low SF consumers. The high SF consumers had a significantly lower FMD (5.4 +/- 2.1 versus 8.8 +/- 2.8%; ANCOVA with BMI and waist circumpherence as covariates: P = 0.025) than the high consumers. Other cardiovascular biomarkers did not significantly differ between the two groups. CONCLUSIONS: This study suggests that high SF consumption in Palermo may be associated with endothelial dysfunction in healthy people, probably indicating that this category of foods should be limited, especially in people at high cardiovascular risk. PMID- 22673181 TI - Immunohistochemical profile of NF-kappaB/p50, NF-kappaB/p65, MMP-9, MMP-2, and u PA in experimental cervical spondylotic myelopathy. AB - STUDY DESIGN: The immunohistochemical profile of nuclear factor-kappa B (NF kappaB)/p50, NF-kappaB/p65, matrix metalloproteinase (MMP)-9, MMP-2, and urokinase-type plasminogen activator (u-PA) proteins was examined in spinal cord tissues coming from rabbits, which underwent chronic cervical spinal cord compression. OBJECTIVE: To study the potential role of NF-kappaB and extracellular matrix proteins under the chronic mechanical compression of the cervical spinal cord. SUMMARY OF BACKGROUND DATA: Cervical spondylotic myelopathy (CSM) is the most common cause of spinal cord dysfunction among adults older than 55 years. Neuronal loss, myelin destruction, axonal degeneration, and glial scar formation are the principal neuropathological features of CSM. However, the biologic pathways that lead to these features remain unclear. METHODS: In this study, we used a new animal experimental model of CSM developed in our laboratory. Briefly, after posterior cervical laminectomy, gradual and progressive compression (during 20 weeks) was achieved by introducing a piece of aromatic polyether (0.07 mm thick) under the C6 lamina in 15 New Zealand rabbits. In control animals (n = 15), the aromatic polyether was implanted and then removed after 60 seconds (sham operation). The immunoreactivity of p50 and p65 subunits of NF-kB, as well as that of MMP-2, MMP-9, and u-PA, was evaluated in paraffin-embedded spinal cord sections coming from both groups. The evaluation was performed using immunohistochemistry technique and the results were analyzed using SPSS for Windows, release 12.0 (SPSS Inc., Chicago, IL). RESULTS: Increased immunoreactivity of both NF-kappaB subunits, p50 and p65, as well as MMP-2, MMP 9, and u-PA was demonstrated in animals with CSM in comparison with controls. Statistical analysis of the results revealed strong positive correlation between NF-kappaB subunits immunoreactivity and that of MMP-9, MMP-2, and u-PA. CONCLUSION: There is a strong correlation between the immunoexpression of NF kappaB/p50, NF-kappaB/p65, MMP-2, MMP-9, u-PA, and CSM. PMID- 22673182 TI - Visual backward-masking performance in a longitudinal study of early onset schizophrenia. AB - The aim of the present study was to examine the effect of visual backward-masking (VBM) in patients with early onset schizophrenia (EOS, n=28) compared to healthy controls (n=80) at baseline and at one- and two-year follow-ups. Seventeen patients and 40 controls performed a VBM task at all three sessions, which included five different interstimuli intervals (ISI) at 16.5, 33.5, 49.5, 116 and 166ms, and an additional no-masking control task. Patients with EOS revealed no impairment of VBM performance at baseline and at the two follow-ups compared to healthy controls at one- and two-year follow-ups. However, the patients demonstrated a deficit of simple early visual processing. Both groups showed effects of development over a period of 24 months for the shortest ISIs. PMID- 22673183 TI - Invasive breast cancer induces laminin-332 upregulation and integrin beta4 neoexpression in myofibroblasts to confer an anoikis-resistant phenotype during tissue remodeling. AB - INTRODUCTION: Although development of anoikis-resistant myofibroblasts during tissue remodeling is known to be associated with tumor invasion, the mechanism by which myofibroblasts become resistant to anoikis is unknown. We previously demonstrated laminin-332 upregulation in the fibrosis around invasive ductal carcinoma (IDC). Because laminin-332 promotes cell survival through binding to integrins, we hypothesized that invasive breast cancer cells confer an anoikis resistant phenotype on myofibroblasts by upregulating laminin-332 expression during tissue remodeling. Here, we demonstrate that invasive breast cancer cells induce laminin-332 upregulation and integrin beta4 neoexpression in myofibroblasts to confer an anoikis-resistant phenotype. METHODS: Three types of fibroblasts were isolated from the tumor burden, the fibrosis, and normal tissue of patients with early stage IDC (less than 10 mm diameter), designated cancer associated fibroblasts (CAFs), interface fibroblasts (InFs), and normal breast fibroblasts (NBFs), respectively. To investigate direct and indirect crosstalk with tumor cells, fibroblasts were co-cultured with invasive MDA-MB-231 or noninvasive MCF7 cells or in conditioned medium. Anoikis resistance of fibroblasts was measured by cell viability and caspase-3 activity after incubation on poly-HEMA coated plates for 72 hours. Involvement of laminin 332/integrin alpha3beta1 or alpha6beta4 signaling in anoikis resistance was confirmed by treatment with purified laminin-332 or blocking antibodies against laminin-332, integrin beta1, or integrin beta4. RESULTS: MDA-MB-231 cells induced laminin-332 upregulation and integrin beta4 neoexpression in fibroblasts, leading to anoikis resistance. InFs showed a higher endogenous level of laminin-332 than did CAFs and NBFs. After stimulation with MDA-MB-231-conditioned medium, laminin 332 expression of InFs was dramatically increased and maintained under anoikis conditions. Laminin-332 upregulation was also observed in CAFs and NBFs, but at a lower level than in InFs. Laminin-332 induced Akt (Ser473) phosphorylation by binding to integrin alpha3beta1. Integrin beta4 neoexpression induced laminin-332 independent Rac1 activation and promoted anoikis resistance in fibroblasts approximately twofold more effectively than did laminin-332, regardless of the type of fibroblast. In addition, integrin beta4 expression suppressed fibroblast aggregation in conditions of anoikis. CONCLUSION: Invasive breast cancer cells confer an anoikis-resistant phenotype on myofibroblasts during tissue remodeling by inducing laminin-332 upregulation and integrin beta4 neoexpression. Interface fibroblasts appear to be the primary myofibroblasts that interact with invasive tumor cells during tissue remodeling. PMID- 22673185 TI - Melatonin modulates the GABAergic response in cultured rat hippocampal neurons. AB - In the present study, we investigated the effect of melatonin on the GABA-induced current (I(GABA) and GABAergic miniature inhibitory postsynaptic currents (mIPSCs) in cultured rat hippocampal neurons using the whole-cell patch-clamp technique. We found that melatonin rapidly and reversibly enhanced I(GABA) in a dose-dependent manner, with an EC50 of 949 MUM. Melatonin markedly enhanced the peak amplitude of a subsaturating I(GABA) but not that of a saturating I(GABA). Interestingly, melatonin was effective only when GABA and melatonin were applied together. Furthermore, the effect of melatonin on I(GABA) was voltage-independent and did not change the ion selectivity of the GABA(A) receptor. The melatonin enhancement on I(GABA) can not be blocked by luzindole, a melatonin receptor antagonist, indicating that melatonin-induced I(GABA) enhancement was not via activation of its own membrane receptors. However, this enhancement may be mediated via high-affinity benzodiazepine sites as it was inhibited by the classical benzodiazepine antagonist flumazenil, suggesting an allosteric modulation of melatonin by binding to the sites of GABA(A) receptors. In addition, melatonin increased both amplitude and frequency of GABAergic mIPSCs, indicating that melatonin enhances GABAergic inhibitory transmission. Hence, our observation that melatonin has an enhancing effect on the GABAergic system may implicate a potential pathway for the neuroprotective effects of melatonin. PMID- 22673186 TI - [Migration to the left cavities of an interatrial communication closure device]. PMID- 22673187 TI - Comparing exposure metrics for classifying 'dangerous heat' in heat wave and health warning systems. AB - Heat waves have been linked to excess mortality and morbidity, and are projected to increase in frequency and intensity with a warming climate. This study compares exposure metrics to trigger heat wave and health warning systems (HHWS), and introduces a novel multi-level hybrid clustering method to identify potential dangerously hot days. Two-level and three-level hybrid clustering analysis as well as common indices used to trigger HHWS, including spatial synoptic classification (SSC), and the 90th, 95th, and 99th percentiles of minimum and relative minimum temperature (using a 10 day reference period), were calculated using a summertime weather dataset in Detroit from 1976 to 2006. The days classified as 'hot' with hybrid clustering analysis, SSC, minimum and relative minimum temperature methods differed by method type. SSC tended to include the days with, on average, 2.5 degrees C lower daily minimum temperature and 5.3 degrees C lower dew point than days identified by other methods. These metrics were evaluated by comparing their performance in predicting excess daily mortality. The 99th percentile of minimum temperature was generally the most predictive, followed by the three-level hybrid clustering method, the 95th percentile of minimum temperature, SSC and others. Our proposed clustering framework has more flexibility and requires less substantial meteorological prior information than the synoptic classification methods. Comparison of these metrics in predicting excess daily mortality suggests that metrics thought to better characterize physiological heat stress by considering several weather conditions simultaneously may not be the same metrics that are better at predicting heat related mortality, which has significant implications in HHWSs. PMID- 22673188 TI - Russell body duodenitis: a histopathological and molecular approach to a rare clinical entity. AB - Russell bodies are pink eosinophilic accumulations within plasma cells. To date, two hypotheses have attempted to elucidate the biological events behind the formation of these bodies. One theory sustains that such bodies constitute cytoplasmic accumulation of immunoglobulin derivatives contained in the perinuclear cistern of the smooth endoplasmic reticulum because of an increased synthesis or altered secretion. On the other hand, since its initial description in the medical literature, several authors have attributed the formation of such bodies to the presence of microorganisms such as in the case of Russell body gastritis and its association to Helicobacter pylori infection. In an attempt to possibly characterize the presence of an infectious organism, we performed a thorough biomolecular analysis on a case of a 69-year-old female presenting with Russell body duodenitis which, to the best of our knowledge, constitutes the second report of this clinical entity in the English literature. In light that the events behind formation of such bodies in H. pylori-negative individuals remain unclear, we hypothesize on the possible pathways that could have led to their reactive mechanical and immune derivation. PMID- 22673189 TI - Generation of induced pluripotent stem cells from Asian patients with chronic neurodegenerative diseases. AB - Induced pluripotent stem (iPS) cells derived from disease patients are an invaluable resource for biomedical research and may provide a source for replacement therapies. In this study, we have generated iPS cells from Asian patients with chronic degenerative diseases of the nervous system, including spinal muscular atrophy (SMA), Parkinson disease (PD) and amyotrophic lateral sclerosis (ALS) by transduction with four factors (KLF4, SOX2, OCT4 and c-MYC). All of the iPS cells showed pluripotency similar to that of human embryonic stem cells (hESCs) and were able to differentiate into various somatic cell types in vitro and in vivo. Furthermore, the iPS cells also can be committed to differentiate into neural cells, the cell type that is affected in chronic degenerative diseases. Therefore, the patient-specific iPS cells we generated offer a cellular model in which to investigate disease mechanisms, discover and test novel drugs and develop new therapies for chronic neurodegenerative diseases. PMID- 22673190 TI - Risk profiles for mild cognitive impairment vary by age and sex: the Sydney Memory and Ageing study. AB - OBJECTIVES: : To examine age- and sex-related differences in risk and protective factors for mild cognitive impairment (MCI) in community-based elderly individuals. DESIGN: : Cross-sectional study. SETTING: : The population-based Sydney Memory and Ageing Study. PARTICIPANTS: : A total of 757 nondemented, community-dwelling elderly individuals from an English-speaking background categorized as younger (70-79 years) or older (80-90 years). MEASUREMENTS: : Risk of MCI was determined for sociodemographic, lifestyle, and cardiac, physical, mental, and general health factors using age- (and sex-) adjusted multiple regressions comprising initially significant univariate factors. RESULTS: : The point prevalence of MCI within our sample was 39.1% overall: it was lowest in younger women (32.3%) and similar across men and older women (41.9%-43.6%). The risk of MCI across all participants was increased by the APOE ?4 allele, high homocysteine, and heart disease; and decreased by better odor identification, visual acuity, and mental activity. Risk factors in all younger participants were slow 6-m walk, poor odor identification, and high homocysteine. Risk of MCI was associated in younger women with history of depression, less mental activity, slower 6-m walk, poorer visual acuity, and higher homocysteine; and in younger men with poorer odor identification and higher homocysteine. Older participants showed no significant risk factors for MCI, except for poorer visual acuity in men. Supporting these findings were statistically significant interactions that reflected the differences in risk factor profiles between age and/or sex groups. CONCLUSIONS: : Risk factors for MCI differ in men and women and vary with age. This has implications for preventing MCI and possibly dementia. PMID- 22673191 TI - Impact of information about obesity genomics on the stigmatization of overweight individuals: an experimental study. AB - Advances in genomic technologies are rapidly leading to new understandings of the roles that genetic variations play in obesity. Increasing public dissemination of information regarding the role of genetics in obesity could have beneficial, harmful, or neutral effects on the stigmatization of obese individuals. This study used an online survey and experimental design to examine the impact of genetic versus non-genetic information on obesity stigma among self-perceived non overweight individuals. Participants (n = 396) were randomly assigned to read either genetic, non-genetic (environment), or gene-environment interaction obesity causal information. A total of 48% of participants were female; mean age was 42.7 years (range = 18-86 years); 75% were white; 45.2% had an annual household income of less than $40,000; mean BMI was 23.4 kg/m(2). Obesity stigma was measured using the Fat Phobia Scale - short form (FPS-S). After reading the experimental information, participants in the genetic and gene-environment conditions were more likely to believe that genetics increase obesity risk than participants in the non-genetic condition (both P < 0.05), but did not differ on obesity stigma. Obesity stigma was higher among whites and Asians than Hispanics and African Americans (P = 0.029), and associated with low self-esteem (P = 0.036). Obesity stigma was also negatively associated with holding 'germ or virus' (P = 0.033) and 'overwork' (P = 0.016) causal beliefs about obesity, and positively associated with 'diet or eating habits' (P = 0.001) and 'lack of exercise' (P = 0.004) causal beliefs. Dissemination of brief information about the role of genetics in obesity may have neither a beneficial nor a harmful impact on obesity stigmatization compared with non-genetic information among self perceived non-overweight individuals. PMID- 22673192 TI - Functional interplay between p63 and p53 controls RUNX1 function in the transition from proliferation to differentiation in human keratinocytes. AB - The interfollicular epidermis is continuously renewed, thanks to a regulated balance between proliferation and differentiation. The DeltaNp63 transcription factor has a key role in the control of this process. It has been shown that DeltaNp63 directly regulates Runt-related transcription factor 1 (RUNX1) transcription factor expression in mouse keratinocytes. The present study showed for the first time that RUNX1 is expressed in normal human interfollicular epidermis and that its expression is tightly regulated during the transition from proliferation to differentiation. It demonstrated that DeltaNp63 directly binds two different RUNX1 regulatory DNA sequences and modulates RUNX1 expression differentially in proliferative or differentiated human keratinocytes. It also showed that the regulation of RUNX1 expression by DeltaNp63 is dependent on p53 and that this coregulation relies on differential binding and activation of RUNX1 regulatory sequences by DeltaNp63 and p53. We also found that RUNX1 inhibits keratinocyte proliferation and activates directly the expression of KRT1, a critical actor in early keratinocyte differentiation. Finally, we described that RUNX1 expression, similar to DeltaNp63 and p53, was strongly expressed and downregulated in basal cell carcinomas and squamous cell carcinomas respectively. Taken together, these data shed light on the importance of tight control of the functional interplay between DeltaNp63 and p53 in regulating RUNX1 transcription factor expression for proper regulation of interfollicular epidermal homeostasis. PMID- 22673194 TI - A life with horses: it's been a great ride! AB - In 2010 Doug Antczak was the recipient of the Distinguished Veterinary Immunologist Award of the Veterinary Immunology Committee of the International Union of Immunological Societies. Dr. Antczak is the Dorothy Havemeyer McConville Professor of Equine Medicine at the Baker Institute for Animal Health in the College of Veterinary Medicine at Cornell University. His research focuses on immunological and genetic aspects of the fetal-maternal relationship in the horse. This includes studies of major histocompatibility complex (MHC) genes and molecules, the regulation of their expression in the placenta, the composition and function of uterine lymphocytes, and alterations in maternal immune reactivity during pregnancy. For this research Dr. Antczak developed a herd of purpose-bred horses selected for homozygosity at the MHC. These horses are a unique genetic resource in equine immunology. During his career Dr. Antczak has mentored over 20 graduate students and post-doctoral fellows, many of whom have gone on to independent careers in immunology research. Dr. Antczak has made contributions to equine immunology, genetics, and reproduction, and collaborated widely with scientists in each of these disciplines. Through his relationship with the Havemeyer Foundation, Dr. Antczak has been a catalyst for cooperative research through a series of Havemeyer Foundation Workshops initiated over 25 years ago. Since 1995 he has been a principal participant in the international Horse Genome Project collaboration furthering his equine immunology research through genomic applications. In 2009 Dr. Antczak was inducted into the University of Kentucky's Equine Research Hall of Fame. PMID- 22673193 TI - Silencing of Twist1 sensitizes NSCLC cells to cisplatin via AMPK-activated mTOR inhibition. AB - Twist1 is highly expressed in primary and metastatic non-small cell lung cancer (NSCLC), and thus acts as a critical target for lung cancer chemotherapy. In the current study, we investigated the underlying mechanism initiated by silencing of Twist1 that sensitizes NSCLC cells to cisplatin. Silencing of Twist1 triggered ATP depletion, leading to AMP-activated protein kinase (AMPK)-activated mammalian target of rapamycin (mTOR) inhibition in NSCLC cells. AMPK-induced mTOR inhibition, in turn, resulted in downregulation of ribosome protein S6 kinase 1 (S6K1) activity. Downregulation of mTOR/S6K1 reduced Mcl-1 protein expression, consequently promoting sensitization to cisplatin. Overexpression of Mcl-1 reduced PARP cleavage induced by cisplatin and Twist1 siRNA, suggesting that this sensitization is controlled through Mcl-1 expression. Interestingly, cells treated with Twist1 siRNA displayed upregulation of p21(Waf1/CIP1), and suppression of p21(Waf1/CIP1) with specific siRNA further enhanced the cell death response to cisplatin/Twist1 siRNA. In conclusion, silencing of Twist1 sensitizes lung cancer cells to cisplatin via stimulating AMPK-induced mTOR inhibition, leading to a reduction in Mcl-1 protein. To our knowledge, this is the first report to provide a rationale for the implication of cross-linking between Twist1 and mTOR signaling in resistance of NSCLC to anticancer drugs. PMID- 22673195 TI - Canine cerebral leishmaniasis: potential role of matrix metalloproteinase-2 in the development of neurological disease. AB - Matrix metalloproteinases (MMPs) are a group of calcium- and zinc-dependent endopeptidases that are involved in maintaining the extracellular matrix. MMP-2 and MMP-9 are thought to be related to the disruption of the blood-brain-barrier (BBB) by their ability to cleave type IV collagen, the main component of the basal membrane. To establish the presence of MMP-2 and MMP-9 in the pathogenesis of canine cerebral leishmaniasis, we examined the levels of these metalloproteinases in the cerebrospinal fluid (CSF) and serum of dogs with visceral leishmaniasis and neurological symptoms (n=16) and in the CSF and serum of uninfected healthy dogs (n=10) using zymography. In the CSF of dogs with cerebral leishmaniasis there was a massive presence of active MMP-2, whereas only the levels of both proMMP-2 and proMMP-9 were elevated in the serum. Although the detected MMP activity in the CSF might merely be related to CNS inflammation, these enzymes may also play a collaborative role in the disease progression. Both MMP-2 and MMP-9 are known to target critical constituents of the BBB, and once activated, they may promote cerebral barrier breakdown, allowing the entrance of inflammatory cells and proteins within the nervous system milieu. PMID- 22673196 TI - Electrocardiographic changes in therapeutic hypothermia. AB - INTRODUCTION: During therapeutic hypothermia (TH), electrocardiographic (ECG) abnormalities such as Osborn waves and/or ST-segment elevation have been described. However, the incidence and prognostic value of these ECG changes are uncertain given the small-scale studies that have been carried out to date. The aim of this study is to further evaluate the electrocardiographic changes during TH. METHODS: During a period of 3 years, 81 patients (age 63 +/- 14 years) were included retrospectively. All patients underwent TH after being resuscitated. ECG registrations before, during and after TH were collected and analyzed. Patients were divided into two groups based on the presence or absence of transmural ischemia ST elevation on the first representative ECG upon arrival at the hospital (ST-segment elevation myocardial infarction (STEMI) and non-STEMI). RESULTS: A total of 243 ECGs were analyzed. During TH 24 patients (30%) had Osborn waves, which disappeared in 22 patients (92%) after regaining normal body temperature. The presence of Osborn waves was not associated with age, gender, average pH, electrolytes, or lactate levels and was not associated with excess in hospital mortality. In 10 patients (12%, six non-STEMI patients) new STEMI was observed during TH, which disappeared after TH discontinuation. The STEMI group (44 patients) had significantly more Osborn waves during TH than the non-STEMI group (38.6% vs. 15.2%, odds ratio = 3.508; 95% confidence interval = 1.281 to 9.610). CONCLUSIONS: Hypothermia-induced Osborn waves are relatively common and are not associated with an unfavorable short-term outcome. TH is associated with ECG changes that may mimic STEMI. PMID- 22673198 TI - Methodological considerations in cognitive bias research: the next steps. AB - Field and Christiansen (2012) comment on the importance of establishing and understanding the internal reliability of measures of substance-related cognitive bias, and suggest potential reasons for the poor reliability of some task variants. We agree that the impact of using stimuli personalized to the participant on the reliability of cognitive bias tasks is worthy of systematic investigation. However, some tasks may still be inherently less reliable than others. Ultimately, this debate should be framed within the wider debate on the validity of laboratory models and methods used to assess real-world phenomena. PMID- 22673199 TI - Influence of catch-up growth on IGFBP-2 levels and association between IGFBP-2 and cardiovascular risk factors in Korean children born SGA. AB - Small for gestational age (SGA) at birth and postnatal growth pattern may have an impact on insulin resistance and body composition in their later life. Emerging evidence has indicated that insulin-like growth factor binding protein-2 (IGFBP 2) may be related to insulin sensitivity. The aim of this study was to evaluate insulin resistance and IGFBP-2 levels in SGA children, and to identify the effect of catch-up growth on IGFBP-2 concentration. Serum IGFBP-2 levels were measured in 103 Korean SGA children including 49 prepubertal and 54 pubertal subjects. Anthropometric values, fasting serum levels of metabolic parameters and insulin sensitivity indices were determined. Each prepubertal or pubertal group was subgrouped based on height or weight catch-up growth. The subgroups with weight catch-up showed higher values of BMI, body fat mass, percent body fat, and total cholesterol. Particularly in pubertal children, IGFBP-2 concentration was lower in the subgroup with weight catch-up. Catch-up growth in height did not affect insulin resistance and metabolic parameters. IGFBP-2 levels were inversely correlated with BMI, body fat mass, percent body fat, insulin and leptin levels in both prepubertal and pubertal groups. Additionally in the pubertal group, systolic blood pressure, cholesterol levels were related to IGFBP-2. A strong relationship between IGFBP-2, the insulin sensitivity index, and some cardiovascular risk factors was observed in children born SGA, suggesting that IGFBP-2 might be a promising marker for early recognition of insulin resistance, particularly in children with weight catch-up. PMID- 22673197 TI - Comparison of alcohol impairment of behavioral and attentional inhibition. AB - BACKGROUND: Despite the wealth of studies demonstrating the impairing effects of alcohol on behavioral inhibition, less is known regarding effects of the drug on attentional inhibition (i.e., the ability to ignore distracting stimuli in the environment in order to focus attention on relevant information). The current study examined alcohol impairment of both behavioral and attentional inhibition, as well as potential associations between the two mechanisms of inhibitory control. METHODS: Men (n=27) and women (n=21) performed a measure of behavioral inhibition (cued go/no-go task) and a measure of attentional inhibition (delayed ocular return task) following three doses of alcohol: 0.65 g/kg, 0.45 g/kg, and 0.0 g/kg (placebo). RESULTS: Alcohol impaired both behavioral and attentional inhibition relative to placebo; however, correlational analyses revealed no associations between measures of behavioral and attentional inhibition following any dose. Additionally, men committed more inhibitory failures on the behavioral inhibition task, whereas women committed more inhibitory failures on the attentional inhibition task. CONCLUSIONS: These findings suggest that behavioral and attentional inhibition are equally sensitive to the impairing effects of alcohol, yet represent distinct components of inhibitory control. Additionally, the observed gender differences in control of behavior and attention could have important implications regarding negative consequences associated with alcohol induced disinhibition in men and women. PMID- 22673200 TI - Falsely elevated thyroid hormone levels caused by anti-ruthenium interference in the Elecsys assay resembling the syndrome of inappropriate secretion of thyrotropin. AB - The syndrome of inappropriate secretion of thyrotropin (SITSH) is defined as the inappropriate non-suppression of serum TSH in the presence of elevated free thyroid hormone; TSH-secreting pituitary adenomas and the syndrome of resistance to thyroid hormone are the main etiologies of SITSH. In addition, erroneous thyroid function testing may result in the diagnosis of this syndrome. A 63-year old woman was referred because of suspected SITSH. Laboratory tests showed a normal TSH (0.52 MUIU/L; normal range: 0.5-5.0) measured by sandwich Elecsys, and elevated FT4 (3.8 ng/dL; normal range: 0.9-1.6) and FT3 (7.6 pg/mL; normal range: 2.3-4.0), determined by competitive Elecsys. To exclude possible assay interference, aliquots of the original samples were retested using a different method (ADVIA Centaur), which showed normal FT4 and FT3 levels. Eight hormone levels, other than thyroid function tests measured by competitive or sandwich Elecsys, were higher or lower than levels determined by an alternative analysis. Subsequent examinations, including gel filtration chromatography, suggested interference by substances against ruthenium, which reduced the excitation of ruthenium, and resulted in erroneous results. The frequency of similar cases, where the FT4 was higher than 3.2 ng/dL, in spite of a non-suppressed TSH, was examined; none of 10 such subjects appeared to have method-specific interference. Here, a patient with anti-ruthenium interference, whose initial thyroid function tests were consistent with SITSH, is presented. This type of interference should be considered when thyroid function is measured using the Elecsys technique, although the frequency of such findings is likely very low. PMID- 22673201 TI - Novel psychoactive substances: how to understand the acute toxicity associated with the use of these substances. AB - Since the turn of the 21st century, there has been an increase in the availability and use of novel psychoactive substances (also known as "legal highs") across Europe. Currently, there is limited information available on the potential acute toxicity (harms) associated with the use of these novel psychoactive substances. There are a number of potential data sources that can provide information on the acute toxicity associated with their use: (1) user reports on Internet discussion fora; (2) subpopulation level surveys of self reported harms/unwanted effects (3) regional or national poisons information service accesses for support on presentations to healthcare facilities relating to acute toxicity; (4) case reports/series based on self-reported use or analytically confirmed use; and (5) human volunteer studies assessing potential acute toxicological effects. Each of these data sources has its own limitations, particularly those that are based on self-reported use because there are a number of European studies that show that there is inconsistency in the substance(s) in the "drug" that an individual uses. However, by using a multilayered approach of combining different sources, it is possible to reduce the overall impact of the limitations of any one individual data source. In this review article, we will combine information from these different data sources to describe the pattern of acute toxicity associated with 4 novel psychoactive substances: 1 benzylpiperazine, mephedrone (4-methylmethcathinone), synthetic cannabinoid receptor agonists, and methoxetamine. PMID- 22673202 TI - Determination of inosine triphosphate pyrophosphatase phenotype in human red blood cells using HPLC. AB - BACKGROUND: Thiopurine drugs, widely used in cancer chemotherapy, inflammatory bowel disease, and autoimmune hepatitis, are responsible for common adverse events. Only some of these may be explained by genetic polymorphism of thiopurine S-methyltransferase. Recent articles have reported that inosine triphosphate pyrophosphatase (ITPase) deficiency was associated with adverse drug reactions toward thiopurine drug therapy. Here, we report a weak anion exchange high performance liquid chromatography method to determine ITPase activity in red blood cells and to investigate the relationship with the occurrence of adverse events during azathioprine therapy. METHODS: ITPase activity was assessed by the enzymatic conversion of inosine triphosphate (ITP) to inosine monophosphate (IMP). The reaction was stopped by heating for 3 minutes at 120 degrees C. IMP, inosine diphosphate, and ITP were analyzed on a Hypersil APS-2 column, a weak anion exchange phase that exhibits both ionic and hydrophobic properties. RESULTS: The chromatographic method reported allows the analysis of IMP, inosine diphosphate, and ITP in a single run in <12.5 minutes. The method was linear in the range 5-1500 MUmole/L of IMP. Intraassay and interassay precisions were <5% for red blood cell lysates supplemented with 50, 500, and 1000 MUmole/L IMP. Km and Vmax evaluated by Lineweaver-Burk plot were 677.4 MUmole/L and 19.6 MUmole.L.min, respectively. The frequency distribution of ITPase from 73 patients was investigated. CONCLUSIONS: The method described is useful to determine the ITPase phenotype from patients on thiopurine therapy and to investigate the potential relation between ITPase deficiency and the occurrence of adverse events. PMID- 22673203 TI - [Impact of body mass index on men in their 20s and the effects of subsequent changes in body weight upon the rates of hypertension and diabetes and medical costs in their 40s]. AB - OBJECTIVE: To investigate the impact of body mass index (BMI) of men in their 20s and the effects of subsequent changes in body weight upon medication rates, prevalence of hypertension and diabetes, and medical costs in their 40s. SUBJECTS AND METHODS: A total of 10,125 men who were in their 20s in 1989 were recruited as subjects and grouped according to their BMI and a combination of BMI and increase in body weight over a 20-year period. A logistic regression analysis was performed to evaluate subsequent medication rates, prevalence of hypertension and diabetes, and consultation rate. Analysis of covariance was performed for mean medical costs on the basis of the BMI value in their 20s. All data were adjusted for age in 1989 and changes in body weight over the subsequent 20 yr. RESULTS: A mean increase of 7 kg in body weight was observed over the 20-year period. Medication rates and prevalence of hypertension and diabetes in the men in their 40s increased significantly in correlation with the BMI values in their 20s (men with higher BMI showed higher medication and symptom prevalence rates). The 25.0 or higher BMI group showed a 6.81-fold higher prevalence of hypertension and a 16.62-fold higher prevalence of diabetes than the 18.5-19.9 BMI group. Similarly, men with higher BMI values in their 20s incurred greater outpatient and total medical costs in their 40s. The mean total medical costs in 2009 of men in the 18.5 or lower BMI group in their 20s was 818.7 yen and that for men in the 25.0 or higher BMI group was 5,311.5 yen. Furthermore, men in their 40s showed increased risk of hypertension and diabetes, if their body weight increased by 10 kg or more in the subsequent 20 yr, even when they had BMI values between 20.0 and 24.9 in their 20s. DISCUSSION: Men with high BMI values in their 20s showed higher prevalence of hypertension and diabetes and incurred greater medical costs in their 40s. Even men with a BMI of less than 25.0 in their 20s, showed increases in the prevalence of hypertension and diabetes which were dependent on their weight gain in the subsequent years. Healthcare activities in Japanese corporations based on lifetime employment should promote anti-obesity strategies among young employees and help not only those employees who are obese but also those who are not controlling their weight. PMID- 22673204 TI - Immunohistochemical localization of inhibin/activin subunits in the wild ground squirrel (Citellus dauricus Brandt) ovary. AB - The intraovarian function of gonadally produced inhibin and activin has been extensively studied in experimental models for decades, yet their presence and function have been rarely reported in wild rodents. With our seasonal breeding model, the wild ground squirrel, we aimed to investigate the possible roles of these peptides in the seasonal folliculogenesis. Immunohistochemical staining and Western blotting have been used to detect the cellular localization and expression patterns of inhibin/activin subunits (alpha, beta(A) and beta(B)). In the breeding season ovary, all three subunits were present in granulosa cells, theca cells of antral follicles and interstitial cells, with the strongest immunostaining in granulosa cells. Following ovulation, the corpora lutea become a major site of inhibin/activin synthesis. In the nonbreeding season ovary, inhibin/activin alpha and beta(A) subunits were weakly immunopositive in granulosa cells of early stage follicles, while beta(B) subunit was undetectable. The expression level of inhibin/activin subunit proteins were generally higher in the ovaries of the breeding season, and then decreased to a relatively low level during the nonbreeding season. The dynamic expression of inhibin/activin subunits indicated that they might play important paracrine and/or autocrine roles during the seasonal folliculogenesis of the wild ground squirrel. PMID- 22673206 TI - Selenium and vitamin E improve the in vitro maturation, fertilization and culture to blastocyst of porcine oocytes. AB - Selenium (Se) and vitamin E (Vit-E), as integral parts of antioxidant systems, play important roles for sperm and embryos in vitro. In this study, the effects of Se and Vit-E on the maturation, in vitro fertilization and culture to blastocysts of porcine oocytes and accumulation of ammonia in the culture medium during different development stages were investigated. The maturation was performed in modified tissue culture medium (mTCM)-199 supplemented with 10% (v/v) porcine follicular fluid, the fertilization medium was modified Tyrode's albumin lactate pyruvate (mTALP), and the embryo culture medium was modified North Carolina State University (mNCSU)-23. Se in the form of sodium selenite (SS) and seleon-L-methionine (SeMet) and Vit-E at different concentrations were also used. The incorporation and oxidation of (14)C(U)-glucose were assessed with a liquid scintillation counter. In this study, SeMet and SeMet+Vit-E increased oocyte maturation, fertilization and incorporation and oxidation of (14)C(U) glucose significantly (P<0.05) compared with the control and other treatments. In addition, embryo development, specifically in terms of the numbers of morulae and blastocysts, significantly increased (P<0.05) with SeMet and SeMet+Vit-E. In contrast, the accumulation of ammonia was reduced with SeMet and SeMet+Vit-E compared with other treatments. These findings indicate that SeMet and SeMet+Vit E may play important roles in reducing the accumulation of ammonia and subsequently in increasing the rate of maturation of porcine oocytes and fertilization, as well as development of the blastocyst and utilization of glucose in in vitro maturation, fertilization and culture to blastocysts of porcine oocytes. PMID- 22673205 TI - Seasonal changes in immunoreactivity of vascular endothelial factor and its receptors VEGFR1 and VEGFR2 in the uterus of wild ground squirrels (Citellus dauricus Brandt). AB - In this study, we investigated the immunoreactivity of vascular endothelial growth factor (VEGF) and its receptors flt-1 (VEGFR1) and the kinase domain receptor (KDR/Flk-1, VEGFR2) in the uteri of the wild ground squirrels during the estrous period, early pregnancy and nonbreeding period. Cellular localizations of VEGF, VEGFR1 and VEGFR2 were detected by immunohistochemistry, and total proteins were extracted from uterine tissue in the estrous period, early pregnancy and nonbreeding period for Western blotting analysis. In addition, plasma estradiol 17beta and progesterone concentrations were measured by radioimmunoassay. Stronger positive staining of VEGF was found in luminal epithelial cells and glandular cells, and its receptors (VEGFR1 and VEGFR2) were observed in stromal cells in the estrous period and early pregnancy compared with the nonbreeding period. The protein levels of VEGF, VEGFR1 and VEGFR2 were significantly higher in the estrous period and early pregnancy as compared with the nonbreeding period. Besides, plasma estradiol-17beta and progesterone concentrations were higher in the estrous period and early pregnancy than in the nonbreeding period, suggesting that the immunoreactivities of VEGF, VEGFR1 and VEGFR2 were correlated with changes in plasma estradiol-17beta and progesterone concentrations. These results suggested that VEGF and its receptors may be involved in the regulation of seasonal changes in the uterine functions of wild female ground squirrels. PMID- 22673207 TI - Structure of the genomic sequence comprising the immunoglobulin heavy constant (IGHC) genes from Sus scrofa. AB - The number of immunoglobulin heavy chain (IGH) constant genes (IGHC) varies among mammals. To annotate the porcine IGHC genes, we sequenced the entire IGHC containing genomic region from a single porcine haplotype. The resulting contiguous sequence included in 5' the IGH diversity (D) gene cluster and in 3' TMEM121, which flank the IGHC cluster in the human genome, suggesting that we had obtained the entire genomic region containing porcine IGHC. This region was about 190-kb long, in good agreement with those of other mammals. The porcine IGHC cluster contained 10 genes, IGHM, IGHD, six IGHG genes, IGHE and IGHA. The porcine IGHG genes formed a cluster between IGHD and IGHE, with IGHG3 considered as the most ancient IGHG gene, located at the beginning of the IGHG cluster. Furthermore, the porcine sequence contained two IGHG5 and two IGHG6 genes, but no IGHG genes for IgG2 and IgG4, suggesting flexibility within the IGHG cluster. We also recorded structural differences in the switch regions of the IGHC genes that may be important in their transcription. This haplotype can serve as a reference for future studies on other haplotypes and for functional analysis of porcine immunoglobulin (IG) isotypes. PMID- 22673208 TI - Molecular analysis of the binding mode of Toll/interleukin-1 receptor (TIR) domain proteins during TLR2 signaling. AB - Toll-like receptor (TLR) signaling is initiated by the binding of various adaptor proteins through ligand-induced oligomerization of the Toll/interleukin-1 receptor (TIR) domains of the TLRs. TLR2, which recognizes peptidoglycans, lipoproteins or lipopeptides derived from Gram-positive bacteria, is known to use the TIR domain-containing adaptor proteins myeloid differentiating factor 88 (MyD88) and MyD88 adaptor-like (Mal). Molecular analyses of the binding specificity of MyD88, Mal, and TLR2 are important for understanding the initial defenses mounted against Gram-positive bacterial infections such as Streptococcus pneumoniae. However, the detailed molecular mechanisms involved in the multiple interactions of these TIR domains remain unclear. Our study demonstrates that the TIR domain proteins MyD88, Mal, TLR1, and TLR2 directly bind to each other in vitro. We have also identified two binding interfaces of the MyD88 TIR domain for the TLR2 TIR domain. A residue at these interfaces has recently been found to be mutated in innate immune deficiency patients. These novel insights into the binding mode of TIR proteins will contribute to elucidation of the mechanisms underlying innate immune deficiency diseases, and to future structural studies of hetero-oligomeric TIR-TIR complexes. PMID- 22673209 TI - Molecular cloning, characterization and expression of goose Toll-like receptor 5. AB - Toll-like receptors (TLRs) are pattern recognition receptors (PRRs) that are vital to activation of the innate immune system in response to invading pathogens through their recognition of pathogen-associated molecular patterns (PAMPs). TLR5 is responsible for the recognition of bacterial flagellin in vertebrates. In this study, we cloned the goose TLR5 gene using rapid amplification of cDNA ends (RACE). The open reading frame (ORF) of goose TLR5 cDNA is 2583 bp in length and encodes an 860 amino acid protein. The entire coding region of the TLR5 gene was successfully amplified from genomic DNA and contained a single exon. The putative amino acid sequence of goose TLR5 consisted of a signal peptide sequence, 11 leucine-rich repeat (LRR) domains, a leucine-rich repeat C-terminal (LRR-CT) domain, a transmembrane domain and an intracellular Toll-interleukin-1 receptor (TIR) domain. The amino acid sequence of goose TLR5 shared 50.5% identity with human (Homo sapiens), 49.8% with mouse (Mus musculus) and 82.7% with chicken (Gallus gallus). The goose TLR5 gene was highly expressed in the spleen, liver and brain; moderately expressed in PBMCs, kidney, lung, heart, bone marrow, small intestine and large intestine; and minimally expressed in the cecum. HEK293 cells transfected with goose TLR5 and NF-kappaB-luciferase containing plasmids significantly responded to flagellin from Salmonella typhimurium indicating that it is a functional TLR5 homologue. In response to infection with S. enterica serovar Enteritidis (SE), the level of TLR5 mRNA significantly increased over the control in PBMCs at 1 d post infection (p.i.) and was slightly elevated in the spleen at 1 d or 3 d p.i. IL-6 was expressed below control levels in PBMCs but was upregulated in the spleen. In contrast to IL-6, an evident decrease in the expression level of IL-8 was observed in both PBMCs and spleens at 1 d or 3 d p.i. SE challenge also resulted in an increase in the mRNA expression of IL-18 and IFN-gamma in PBMCs and the spleen. These results imply that the expression of goose TLR5 is differentially regulated in various tissues and may participate in the immune response against bacterial pathogens. PMID- 22673210 TI - Inhibition of the transcription factor c-Jun by the MAPK family, and not the NF kappaB pathway, suggests that peanut extract has anti-inflammatory properties. AB - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is involved in inflammatory responses in atherosclerosis. We propose an in vitro cellular assay to evaluate the anti-inflammatory mechanisms of potential modifiers such as food extracts. In the current model we assessed an anti-inflammatory effect of polyphenol-rich peanut extract in lipopolysaccharide (LPS)-induced THP-1 monocytes. METHODS: THP 1 monocytes were incubated with peanut extract (5, 25, 50 and 100 MUg/mL) consisting of 39% flavonols, 37% flavanols and 24% phenolic acid (or BAY 11-7082 (5 MUM) as experiment control) for 1 h and then stimulated with LPS (500 ng/mL) for 4 h. Cytotoxicity was measured as lactate dehydrogenase (LDH) activity release. NF-kappaB and MAPK family were determined by TransAm kit while TNF-alpha mRNA levels and its mRNA stability by RT-PCR. Intra- and extracellular TNF-alpha protein was measured by ELISA, and TNF-alpha converting enzyme (TACE) activity by a fluorimetric assay. RESULTS: Peanut extract inhibited the maximal LPS-induced extracellular TNF-alpha protein secretion by 18%, 29% and 47% at 25, 50 and 100 MUg/mL, respectively (P<0.05). LPS stimulation revealed that 85% of TNF-alpha was released extracellularly while 15% remained intracellular. Peanut extract did not modify NF-kappaB but, instead, reduced c-Jun transcription factor activity (P<0.05), decreased TNF-alpha mRNA (albeit non-significantly) and had no effect on mRNA stability and TACE activity. CONCLUSION: Polyphenol-rich peanut extract reduces extracellular TNF-alpha protein by inhibiting c-Jun transcription factor from MAPK family, suggesting an anti-inflammatory effect. The proposed THP-1 monocyte model could be used to assess food extract impact (site and size effects) on the inflammation pathway. PMID- 22673211 TI - Roles of Trypanosoma cruzi calreticulin in parasite-host interactions and in tumor growth. AB - In Latin America, there are about 10-12 million people infected with Trypanosoma cruzi, the agent of Chagas' disease, one of the most important neglected tropical parasitism. Identification of molecular targets, specific for the aggressor or host cells or both, may be useful in the development of pharmacological and/or immunological therapeutic tools. Classic efforts in Chagas' disease explore those strategies. Although the immune system frequently controls parasite aggressions, sterile immunity is seldom achieved and chronic interactions are thus established. However, laboratory-modified immunologic probes aimed at selected parasite targets, may be more effective than their unmodified counterparts. Calreticulin (CRT) from vertebrates is a calcium binding protein, present mainly in the endoplasmic reticulum (ER), where it directs the conformation of proteins and controls calcium levels. We have isolated, gene-cloned, expressed and characterized T. cruzi calreticulin (TcCRT). Upon infection, the parasite can translocate this molecule from the ER to the surface, where it inhibits both the classical and lectin complement pathways. Moreover, by virtue of its capacity to bind and inactivate first complement component C1, it promotes parasite infectivity. These two related properties reside in the central domain of this molecule. A different domain, amino terminal, binds to endothelial cells, thus inhibiting their angiogenic capacity. Since tumor growth depends, to a large extent on angiogenesis, their growth is also inhibited. PMID- 22673212 TI - T cell-specific deletion of EFNB2 minimally affects T cell development and function. AB - BACKGROUND: Eph kinases and their ephrin ligands (EFN) are all cell surface molecules, capable of transmitting signals in both directions (1, 2). Such bidirectional signaling is called forward (from EFNs to Ephs) and reverse (from Ephs to EFNs) signaling. Eph family kinases have 15 members, divided into A and B subfamilies. Ephrin ligands have 9 members, also classified into A and B families. Ephs and ephrins interact promiscuously, but EphAs mainly interact with EFNAs, and EphBs with EFNBs. EphB family kinases and their ephrin ligands (EFN) are expressed in the T cell compartment. RESULTS: In this study, using mice with T cell-specific EFNB2 gene knockout (EFNB2 KO mice), we investigated T cell development and function after EFNB2 deletion. EFNB2 KO mice presented normal thymus weight and cellularity. Their thymocyte subpopulations, such as CD4CD8 double positive cells and CD4 and CD8 single positive cells, were normally distributed, but there was a significant relative increase of CD4CD8 double negative cells. Flow cytometry analysis revealed that there was a moderate increase in the DN3 subpopulation. This augmented percentage of DN cells was further confirmed in competitive repopulation chimeras, suggesting that EFNB2 is involved in thymocyte development. The EFNB2 KO mice had normal T cell numbers and percentages in the spleen, and the T cells were able to be activated and to proliferate normally upon TCR ligation. Further, EFNB2 KO naive CD4 cells were capable of differentiating into Th1, Th2, Th17 and Treg cells similar to WT naive CD4 cells. CONCLUSIONS: Our results suggest the involvement of EFNB2 in thymocyte development. However, heavy redundancy among Eph/EFN family members prevents the occurrence of detrimental phenotypes in the T cell compartment caused by T cell specific EFNB2 gene null mutation. PMID- 22673213 TI - Transcriptional effects of a lupus-associated polymorphism in the 5' untranslated region (UTR) of human complement receptor 2 (CR2/CD21). AB - Systemic lupus erythematosus (SLE) is a complex autoimmune disease with a strong genetic component that determines risk. A common three single-nucleotide polymorphism (SNP) haplotype of the complement receptor 2 (CR2) gene has been associated with increased risk of SLE (Wu et al., 2007; Douglas et al., 2009), and a less common haplotype consisting of the major allele at SNP1 and minor alleles at SNP2 and 3 confers protection (Douglas et al., 2009). SNP1 (rs3813946), which is located in the 5' untranslated region (UTR) of the CR2 gene, altered transcriptional activity of a CR2 promoter-luciferase reporter gene construct transiently transfected into a B cell line (Wu et al., 2007) and had an independent effect in the protective haplotype (Douglas et al., 2009). In this study, we show that this SNP alters transcriptional activity in a transiently transfected non B-cell line as well as in stably transfected cell lines, supporting its relevance in vivo. Furthermore, the allele at this SNP affects chromatin accessibility of the surrounding sequence and transcription factor binding. These data confirm the effects of rs3813946 on CR2 transcription, identifying the 5' UTR to be a novel regulatory element for the CR2 gene in which variation may alter gene function and modify the development of lupus. PMID- 22673214 TI - Ring-opening metathesis polymerization-derived large-volume monolithic supports for reversed-phase and anion-exchange chromatography of biomolecules. AB - Preparative-scale monolithic columns up to 433.5 mL in volume were prepared via transition metal-catalyzed ring-opening metathesis polymerization (ROMP) from norborn-2-ene (NBE) and trimethylolpropane-tris(5-norbornene-2-carboxylate) (CL) using the 1(st)-generation Grubbs initiator RuCl(2)(PCy(3))(2)(CHPh) (Cy = cyclohexyl) (1) in the presence of a macro- and microporogen, i.e. of 2-propanol and toluene. To prepare large-volume monoliths, bulk polymerizations were completed within borosilicate or PEEK column formats with diameters in the range of 3 to 49 mm. The pore structure of the large-volume monoliths was investigated by electron microscopy and inverse-size exclusion chromatography (ISEC), respectively. Monolithic columns with inner diameters (I.D.s) in the range of 10 49 mm were tested for the separation of a mixture of five proteins, i.e., insulin, cytochrome C, lysozyme, conalbumin, and beta-lactoglobulin. Preparative separation of these proteins was achieved within less than 12 min in a 433.5 mL monolithic column by applying gradient elution in the RP-HPLC mode. Furthermore, weak and strong anion exchangers were prepared via post-synthesis grafting of bicyclo[2.2.1]hept-5-en-2-yl-methyl-N,N-dimethylammonium hydrochloride (4) and bicyclo[2.2.1]hept-5-en-2-ylmethyl-N,N,N-trimethylammonium iodide (5), respectively. The weak and strong anion exchangers were used for the preparative scale separation of 5'-phosphorylated oligodeoxythymidylic acid fragments of d[pT](12-18) at pH values ranging from 5 to 9. PMID- 22673215 TI - Painless, rapidly increasing maxillary swelling and erythematous mucosa: differential diagnosis and therapy. PMID- 22673216 TI - What enrichment lies beyond the dentistry: a tale of discovery. PMID- 22673217 TI - Parameters affecting degree of conversion of dual-cure resin cements in the root canal: FTIR analysis. AB - OBJECTIVE: To evaluate the degree of conversion of dual-cured resin cements applied for luting of translucent and opaque fibre posts. METHODS: Two dual-cured resin cements, RelyX ARC and Nexus 2, were used to cement 2 types of tooth coloured fibre posts, D.T. Light-Post (translucent) and D.T. White-Post (opaque). The degree of conversion for each resin cement was measured. Post-curing polymerization and chemical curing of the cements were also measured. The degree of conversion was measured at various distances (4, 6 and 8 mm) from the tip of the light-curing unit by Fourier transform infrared spectroscopy. The data were analyzed with analysis of variance and post hoc tests (alpha = 0.05). RESULTS: The degree of conversion of the dual-cure cements was significantly higher with the D.T. Light-Posts than with the D.T. White-Posts (p < 0.05). No significant difference was observed in the degree of conversion at different depths for the RelyX ARC resin cement in conjunction with the D.T. Light-Posts (p > 0.05). The overall degree of conversion decreased linearly with increasing distance from the light-curing tip. Monitoring of post-curing polymerization and chemical curing revealed no further increase in degree of conversion after 5 minutes (p > 0.05). CONCLUSION: The translucent fibre posts (D.T. Light-Posts) allowed a significantly higher degree of conversion with dual-cure resin cements than the opaque fibre posts (D.T. White-Posts) because of the light-transmitting property of their optical fibres. PMID- 22673218 TI - Periodontal practice and referral profile of general dentists in Nova Scotia, Canada. AB - BACKGROUND: In contrast to an expected increase in demand for periodontal services with aging of the population, it appears that referrals to periodontists are declining. OBJECTIVE: To determine the extent to which general dentists in Nova Scotia, Canada, provide periodontal and surgical implant therapies and to determine the factors influencing a dentist's decision to provide treatment or refer patients to a specialist. METHODS: A cross-sectional survey study was performed. The survey questionnaire was mailed to all 443 general dentists practising in Nova Scotia in summer 2009. The questionnaire presented several clinical scenarios and asked respondents whether they would treat the patient in the office or refer to a specialist. The data were analyzed by logistic regression. RESULTS: Of the 279 (63.0%) dentists responding to the survey, 272 (61.4% of the total) were eligible for inclusion in the analysis. The majority of dentists reported rendering nonsurgical periodontal therapy, including scaling (98.5%; 262/266), periodontal maintenance (95.9%; 255/266), and treatment for bruxism (95.1%; 252/265). The most common surgical procedures performed by dentists were frenectomy (29.4%; 78/265), gingivectomy (29.3%; 77/263) and crown lengthening procedures (17.0%; 46/271). Eleven factors significantly influenced dentists' decisions to treat or refer patients. The most common criteria used in selecting a periodontist were satisfaction of previous patients, previous success with the treatment, and the personality of and good communications with the periodontist. CONCLUSIONS: In this study, dentists reported rendering nonsurgical periodontal therapy on a wide scale, whereas their involvement in oral or periodontal and implant surgical therapies was limited. PMID- 22673219 TI - Loss of sight caused by calcium hydroxide paste accidentally splashed into the eye during endodontic treatment: case report. AB - Calcium hydroxide, widely used in endodontic treatment, is a strong base that may cause irreversible injury to vital tissue that comes into contact with this substance. We present the first case of a dentist who accidentally splashed endodontic calcium hydroxide into her own eye. After washing with copious amounts of water for several minutes, she was treated in the hospital within 30 minutes of the accident. Because of the burning caused by the base solution, the dentist lost vision in the affected eye. She returned to the hospital several times for treatment of a corneal abscess and corneal fungal infection. She had the keloid that formed between the eyeball and eyelid removed 3 times. Calcium hydroxide can cause blindness when it comes into contact with the eye. Clinicians should take adequate precautions to prevent this serious complication. In case of an accident, it is important to wash the eye efficiently. PMID- 22673220 TI - Management of a deeply impacted mandibular third molar and associated large dentigerous cyst to avoid nerve injury and improve periodontal healing: case report. AB - As dentigerous cysts increase in size, the risk of postsurgical complications increases as well. Emphasis is usually placed on the risk of neurologic damage caused by trauma during and after surgical removal and of mandibular fracture resulting from the large residual bone defect. However, influence on the periodontal status of neighbouring teeth should also be taken into account. In this article, we present an interdisciplinary, safe, minimally invasive approach to treating large dentigerous cysts associated with deeply impacted third molars. A dentigerous cyst is an epithelial-lined pathologic cavity that develops in association with the crown of an unerupted tooth and appears radiographically as a well-circumscribed pericoronal radiolucency. The cyst not only inhibits the eruption of the associated tooth (usually, a mandibular third molar), but can also carry it to unusual positions in the jaw. Dentigerous cysts may enlarge causing extensive bone resorption and even pathologic fracture. The greater the size of the cyst, the higher the risk of neurologic damage caused by trauma during and after surgical removal and of mandibular fracture resulting from the postoperative bone defect.7,8 Moreover, the removal of large cysts can lead to a severe infrabony defect at the root surface of adjacent teeth, jeopardizing their long-term periodontal health. "Orthodontic extraction" is a combined orthodontic surgical approach that decreases the risk of neurologic complications and facilitates the surgical extraction of impacted mandibular third molars that are in close contact with the mandibular canal, even when associated with cystic lesions.13 This case report shows that the interdisciplinary approach is also effective in preventing periodontal breakdown on the distal surface of the adjacent second molar. PMID- 22673221 TI - A tongue mass in a patient with oral lichen planus. PMID- 22673222 TI - Celebrating 50 years of international dental standards. PMID- 22673223 TI - Canadian research team to study markers of alveolar bone loss. PMID- 22673224 TI - Illustration of constrained composition statistical methods in the interpretation of radionuclide concentrations in the moss Pleurozium schreberi. AB - In this work we have used moss Pleurozium schreberi as a bioindicator of radioactive materials in environment. The following radionuclides were determined in moss samples: (137)Cs, (40)K, (210)Pb, (212)Pb, (214)Pb, (214)Bi, (231)Th, (235)U and (228)Ac, but not all of them in each sample. The highest activity concentrations were found for naturally occurring (210)Pb, (40)K and the artificial isotope (137)Cs. Activities of radioisotopes were recalculated into mass concentrations and the statistical methods intended for constrained data processing were used. Analysis of our results showed at most a weak relationship between radioisotope mass concentrations in moss. It was supposed that concentrations of some elements depended on the same, currently unknown, factors. PMID- 22673225 TI - EGF-like factors induce expansion of the cumulus cell-oocyte complexes by activating calpain-mediated cell movement. AB - Cumulus cell-oocyte complex (COC) expansion is obligatory for LH-induced ovulation and is initiated by LH induction of the epidermal growth factor (EGF) like factors that mediate the synthesis of the hyaluronan-rich matrix and hyaluronan-stabilizing factors. COC expansion also involves the movement of cumulus cells within the matrix by mechanisms that have not been characterized. We document herein that two proteases, calpain 2 and to a lesser extent calpain 1, are expressed in cumulus cells and that the proteolytic activity of these enzymes is rapidly and significantly increased in COC isolated from human chorionic gonadotropin-induced ovulatory follicles in vivo. Stimulation of calpain activity was associated with proteolytic degradation of paxillin and talin (two components of focal adhesion complexes), cell detachment, and the formation of cell surface bleb-like protrusions. Injection of a calpain inhibitor in vivo reduced 1) human chorionic gonadotropin-stimulated calpain enzyme activity, 2) cell detachment, 3) membrane protrusion formation, and 4) COC expansion by mechanisms that did not alter Has2 expression. During EGF-like factor induction of COC expansion in culture, calpain activity was increased by ERK1/2 and intracellular Ca(2+) signaling pathways. Inhibition of calpain activity in cultured COC blocked cumulus cell detachment, protrusion formation, and the vigorous movement of cumulus cells. As a consequence, COC expansion was impaired. Collectively, these results show that two highly coordinated processes control COC expansion. One process involves the synthesis of the hyaluronan matrix, and the other mediates cumulus cell detachment and movement. The latter are controlled by calpain activation downstream of the EGF receptor activation of the Ca(2+) pathway and ERK1/2 pathways. PMID- 22673226 TI - Orexin a suppresses gonadotropin-releasing hormone (GnRH) neuron activity in the mouse. AB - GnRH neurons are critical for the central regulation of fertility, integrating steroidal, metabolic and other cues. GnRH neurons appear to lack receptors for many of these cues, suggesting involvement of afferent systems to convey information. Orexin A (orexin) is of interest in this regard as a neuromodulator that up-regulates metabolic activity, increases wakefulness, and affects GnRH/LH release. We examined the electrophysiological response of GnRH neurons to orexin application and how this response changes with estradiol and time of day in a defined animal model. Mice were either ovariectomized (OVX) or OVX and implanted with estradiol capsules (OVX+E). GnRH neurons from OVX+E mice exhibit low firing rates in the morning, due to estradiol-negative feedback, and high firing rates in the evening, due to positive feedback. Orexin inhibited activity of GnRH neurons from OVX mice independent of time of day. In GnRH neurons from OVX+E mice, orexin was inhibitory during the evening, suggesting orexin inhibition is not altered by estradiol. No effect of orexin was observed in OVX+E morning recordings, due to low basal GnRH activity. Inhibitory effects of orexin were mediated by the type 1 orexin receptor, but antagonism of this receptor did not increase GnRH neuron activity during estradiol-negative feedback. Spike pattern analysis revealed orexin increases interevent interval by reducing the number of single spikes and bursts. Orexin reduced spikes/burst and burst duration but did not affect intraburst interval. This suggests orexin may reduce overall firing rate by suppressing spike initiation and burst maintenance in GnRH neurons. PMID- 22673227 TI - The role of bile after Roux-en-Y gastric bypass in promoting weight loss and improving glycaemic control. AB - Gastric bypass leads to the remission of type 2 diabetes independently of weight loss. Our hypothesis is that changes in bile flow due to the altered anatomy may partly explain the metabolic outcomes of the operation. We prospectively studied 12 patients undergoing gastric bypass and six patients undergoing gastric banding over a 6-wk period. Plasma fibroblast growth factor (FGF)19, stimulated by bile acid absorption in the terminal ileum, and plasma bile acids were measured. In canine and rodent models, we investigated changes in the gut hormone response after altered bile flow. FGF19 and total plasma bile acids levels increased after gastric bypass compared with no change after gastric banding. In the canine model, both food and bile, on their own, stimulated satiety gut hormone responses. However, when combined, the response was doubled. In rats, drainage of endogenous bile into the terminal ileum was associated with an enhanced satiety gut hormone response, reduced food intake, and lower body weight. In conclusion, after gastric bypass, bile flow is altered, leading to increased plasma bile acids, FGF19, incretin. and satiety gut hormone concentrations. Elucidating the mechanism of action of gastric bypass surgery may lead to novel treatments for type 2 diabetes. PMID- 22673228 TI - Minireview: effects of different HT formulations on cognition. AB - Evidence from preclinical studies, randomized clinical trials (RCT), and observational studies underscores the importance of distinguishing among the different forms of estrogen and progestogens when evaluating the cognitive effects of hormone therapy (HT) in women. Despite this evidence, there is a lack of direct comparisons of different HT regimens. To provide insights into the effects of different HT formulations on cognition, this minireview focuses on RCT of verbal memory because evidence indicates that HT affects this cognitive domain more than others and because declines in verbal memory predict later development of Alzheimer's disease. Some observational studies indicate that estradiol confers benefits to verbal memory, whereas conjugated equine estrogens (CEE) confer risks. RCT to date show no negative impact of CEE on verbal memory, including the Women's Health Initiative Study of Cognitive Aging. Similarly, the Women's Health Initiative Memory Study showed no negative impact of CEE on dementia. Transdermal estradiol in younger postmenopausal women improved verbal memory in one small RCT but had no effect in another RCT. RCT of oral estradiol in younger and older postmenopausal women had neutral effects on cognitive function. In contrast, RCT show a negative impact of CEE plus medroxyprogesterone acetate on verbal memory in younger and older postmenopausal women. Small RCT show neutral or beneficial effects of other progestins on memory. Overall, RCT indicate that type of progestogen is a more important determinant of the effects of HT on memory than type of estrogen. PMID- 22673229 TI - Proinflammatory actions of glucocorticoids: glucocorticoids and TNFalpha coregulate gene expression in vitro and in vivo. AB - Synthetic glucocorticoids are widely used for treatment of many inflammatory diseases. However, long-term glucocorticoid treatment can cause a variety of negative side effects. A genome-wide microarray analysis was performed in human lung A549 cells to identify genes regulated by both the antiinflammatory steroid dexamethasone (Dex) and the proinflammatory cytokine TNFalpha. Unexpectedly, we discovered that numerous genes were coregulated by treatment with both Dex and TNFalpha. We evaluated the mechanism of coregulation of one of these genes, serpinA3 (alpha-1 antichymotrypsin), a secreted, acute phase protein strongly associated with numerous inflammatory diseases. Up-regulation of serpinA3 requires the presence of both the glucocorticoid receptor and TNFalpha soluble receptor 1. Treatment with Dex or TNFalpha resulted in a 10- to 25-fold increase of serpinA3 mRNA, whereas coadministration of Dex and TNFalpha led to a synergistic increase in serpinA3 mRNA. The naturally occurring glucocorticoid, cortisol, also resulted in a synergistic increase in serpinA3 mRNA levels in A549 cells. Furthermore, in vivo treatment of C57BL/6 mice with Dex and TNFalpha resulted in coregulation of serpinA3 mRNA levels in both lung and liver tissues. Finally, chromatin immunoprecipitation analyses suggest that glucocorticoid receptor binding to the serpinA3 transcriptional start site can be enhanced by the combination of Dex plus TNFalpha treatment of A549 cells. These studies demonstrate that glucocorticoids and proinflammatory compounds can coregulate genes associated with human disease. This discovery may underlie the basis of some of the adverse effects associated with long-term glucocorticoid therapy. PMID- 22673230 TI - Up-regulating relaxin expression by G-quadruplex interactive ligand to achieve antifibrotic action. AB - Myocardial fibrosis is a key pathological change in a variety of heart diseases contributing to the development of heart failure, arrhythmias, and sudden death. Recent studies have shown that relaxin prevents and reverses cardiac fibrosis. Endogenous expression of relaxin was elevated in the setting of heart disease; the extent of such up-regulation, however, is insufficient to exert compensatory actions, and the mechanism regulating relaxin expression is poorly defined. In the rat relaxin-1 (RLN1, Chr1) gene promoter region we found presence of repeated guanine (G)-rich sequences, which allowed formation and stabilization of G quadruplexes with the addition of a G-quadruplex interactive ligand berberine. The G-rich sequences and the G-quadruplexes were localized adjacent to the binding motif of signal transducer and activator of transcription (STAT)3, which negatively regulates relaxin expression. Thus, we hypothesized that the formation and stabilization of G-quadruplexes by berberine could influence relaxin expression. We found that berberine-induced formation of G-quadruplexes did increase relaxin gene expression measured at mRNA and protein levels. Formation of G-quadruplexes significantly reduced STAT3 binding to the promoter of relaxin gene. This was associated with consequent increase in the binding of RNA polymerase II and STAT5a to relaxin gene promoter. In cardiac fibroblasts and rats treated with angiotensin II, berberine was found to suppress fibroblast activation, collagen synthesis, and extent of cardiac fibrosis through up regulating relaxin. The antifibrotic action of berberine in vitro and in vivo was similar to that by exogenous relaxin. Our findings document a novel therapeutic strategy for fibrosis through up-regulating expression of endogenous relaxin. PMID- 22673231 TI - Beyond colour perception: auditory-visual synaesthesia induces experiences of geometric objects in specific locations. AB - Our brain constantly integrates signals across different senses. Auditory-visual synaesthesia is an unusual form of cross-modal integration in which sounds evoke involuntary visual experiences. Previous research primarily focuses on synaesthetic colour, but little is known about non-colour synaesthetic visual features. Here we studied a group of synaesthetes for whom sounds elicit consistent visual experiences of coloured 'geometric objects' located at specific spatial location. Changes in auditory pitch alter the brightness, size, and spatial height of synaesthetic experiences in a systematic manner resembling the cross-modal correspondences of non-synaesthetes, implying synaesthesia may recruit cognitive/neural mechanisms for 'normal' cross-modal processes. To objectively assess the impact of synaesthetic objects on behaviour, we devised a multi-feature cross-modal synaesthetic congruency paradigm and asked participants to perform speeded colour or shape discrimination. We found irrelevant sounds influenced performance, as quantified by congruency effects, demonstrating that synaesthetes were not able to suppress their synaesthetic experiences even when these were irrelevant for the task. Furthermore, we found some evidence for task specific effects consistent with feature-based attention acting on the constituent features of synaesthetic objects: synaesthetic colours appeared to have a stronger impact on performance than synaesthetic shapes when synaesthetes attended to colour, and vice versa when they attended to shape. We provide the first objective evidence that visual synaesthetic experience can involve multiple features forming object-like percepts and suggest that each feature can be selected by attention despite it being internally generated. These findings suggest theories of the brain mechanisms of synaesthesia need to incorporate a broader neural network underpinning multiple visual features, perceptual knowledge, and feature integration, rather than solely focussing on colour sensitive areas. PMID- 22673232 TI - Effects of NIR annealing on the characteristics of al-doped ZnO thin films prepared by RF sputtering. AB - Aluminum-doped zinc oxide (AZO) thin films have been deposited on glass substrates by employing radio frequency (RF) sputtering method for transparent conducting oxide applications. For the RF sputtering process, a ZnO:Al2O3 (2 wt.%) target was employed. In this paper, the effects of near infrared ray (NIR) annealing technique on the structural, optical, and electrical properties of the AZO thin films have been researched. Experimental results showed that NIR annealing affected the microstructure, electrical resistance, and optical transmittance of the AZO thin films. X-ray diffraction analysis revealed that all films have a hexagonal wurtzite crystal structure with the preferentially c-axis oriented normal to the substrate surface. Optical transmittance spectra of the AZO thin films exhibited transmittance higher than about 80% within the visible wavelength region, and the optical direct bandgap (Eg) of the AZO films was increased with increasing the NIR energy efficiency. PMID- 22673233 TI - A conditionally replicating adenovirus carrying interleukin-24 sensitizes melanoma cells to radiotherapy via apoptosis. AB - Combinatorial therapy is the current trend of the development of novel cancer treatments due to the high heterogenous nature of solid tumors. In this study, we investigated the effects of the combined use of a conditionally replicating adenovirus carrying IL-24 (ZD55-IL-24) and radiotherapy on the proliferation and apoptosis of melanoma A375 cells in vitro and in vivo. Compared with either agent used alone, ZD55-IL-24 combined with radiotherapy significantly inhibited cell proliferation, accompanied with increased apoptosis. Radiotherapy did not affect the expression of IL-24 and E1A of ZD55-IL-24-treated cells, but increased the expression of Bax, promoted the activation of caspase-3, while decreasing Bcl-2 levels. Thus, this synergistic effect of ZD55-IL-24 in combination with radiotherapy provides a novel strategy for the development of melanoma therapies, and is a promising approach for further clinical development. PMID- 22673234 TI - The human TLR innate immune gene family is differentially influenced by DNA stress and p53 status in cancer cells. AB - The transcription factor p53 regulates genes associated with a wide range of functions, including the Toll-like receptor (TLR) set of innate immunity genes, suggesting that p53 also modulates the human immune response. The TLR family comprises membrane glycoproteins that recognize pathogen-associated molecular patterns (PAMP) and mediate innate immune responses, and TLR agonists are being used as adjuvants in cancer treatments. Here, we show that doxorubicin, 5 fluorouracil, and UV and ionizing radiation elicit changes in TLR expression that are cell line- and damage-specific. Specifically, treatment-induced expression changes led to increased downstream cytokine expression in response to ligand stimulation. The effect of DNA stressors on TLR expression was mainly mediated by p53, and several p53 cancer-associated mutants dramatically altered the pattern of TLR gene expression. In all cell lines tested, TLR3 induction was p53 dependent, whereas induction of TLR9, the most stress-responsive family member, was less dependent on status of p53. In addition, each of the 10 members of the innate immune TLR gene family tested was differentially inducible. Our findings therefore show that the matrix of p53 status, chromosome stress, and responsiveness of individual TLRs should be considered in TLR-based cancer therapies. PMID- 22673235 TI - Hypoxia-inducible factor-1 alpha in the heart: a double agent? AB - Hypoxia-inducible factor (HIF) is a set of transcription factors that regulate the cellular response to hypoxia. There is a great body of evidence supporting the protective role of HIF-1alpha in cardiovascular pathophysiology, however, newer studies are hinting at a maladaptive and deleterious role of this transcription factor that merits further investigation. There is a general agreement, however, that HIF-mediated responses appear to differ under conditions of acute and chronic oxygen deprivation. The intensity and sustainability of HIF 1alpha activation are major determinants of whether the responses are pathological or beneficial. HIF activation is seen to be beneficial in the setting of acute myocardial ischemia and deleterious in chronic conditions. In this review, we will focus on recent insights into the role of HIF-1alpha in the heart and especially in the setting of ischemic heart disease. PMID- 22673236 TI - Selective angiographic embolization of blunt splenic traumatic injuries in adults decreases failure rate of nonoperative management. AB - BACKGROUND: To determine whether angioembolization (AE) in hemodynamically stable adult patients with blunt splenic trauma (BST) at high risk for failure of nonoperative management (NOM) (contrast blush [CB] on computed tomography, high grade IV-V injuries, or decreasing hemoglobin) results in lower failure rates than reported. METHODS: The records of patients with BST from July 2000 to December 2010 at a Level I trauma center were retrospectively reviewed using National Trauma Registry of the American College of Surgeons. Failure of NOM (FNOM) occurred if splenic surgery was required after attempted NOM. Logistic regression analysis was used to identify factors associated with FNOM. RESULTS: A total of 1,039 patients with BST were found. Pediatric patients (age <17 years), those who died in the emergency department, and those requiring immediate surgery for hemodynamic instability were excluded. Of the 539 (64% of all BST) hemodynamically stable patients who underwent NOM, 104 (19%) underwent AE and 435 (81%) were observed without AE (NO-AE). FNOM for the various groups were as follows: overall NOM (4%), NO-AE (4%), and AE (4%). There was no significant difference in FNOM for NO-AE versus AE for grades I to III: grade I (1% vs. 0%, p = 1), grade II (2% vs. 0%, p = 0.318), and grade III (5% vs. 0%, p = 0.562); however, a significant decrease in FNOM was noted with the addition of AE for grades IV to V: grade IV (23% vs. 3%, p = 0.04) and grade V (63% vs. 9%, p = 0.03). Statistically significant independent risk factors for FNOM were grade IV to V injuries and CB. CONCLUSION: Application of strictly defined selection criteria for NOM and AE in patients with BST resulted in one of the lowest overall FNOM rates (4%). Hemodynamically stable BST patients are candidates for NOM with selective AE for high-risk patients with grade IV to V injuries, CB on initial computed tomography, and/or decreasing hemoglobin levels. LEVEL OF EVIDENCE: III, therapeutic study. PMID- 22673237 TI - Traditional systolic blood pressure targets underestimate hypotension-induced secondary brain injury. AB - BACKGROUND: Vital signs, particularly blood pressure, are often manipulated to maximize perfusion and optimize recovery from severe traumatic brain injury (sTBI). We investigated the utility of automated continuously recorded vital signs to predict outcomes after sTBI. METHODS: Sixty patients with head Abbreviated Injury Scale score >= 3, age >14 years, "isolated" TBI, and need for intracranial pressure monitoring were prospectively enrolled at a single, large urban tertiary care facility. Outcome was measured by mortality and extended Glasgow Outcome Scale (GOSE) at 12 months. Continuous, automated, digital data were collected every 6 seconds for 72 hours after admission, and 5-minute means of systolic blood pressure (SBP) were recorded. We calculated SBP as pressure * time dose (PTD) to describe the cumulative amplitude and duration of episodes above and below clinical thresholds. The extent and duration of the insults were calculated as percent time (%time), PTD, and PTD per day (PTD/D) of defined thresholds (SBP: <90 mm Hg, <100 mm Hg, <110 mm Hg, and <120 mm Hg; mean arterial pressure: <60 mm Hg and <70 mm Hg; heart rate: >100 bpm and >120 bpm; and SpO(2): <88% and <92%) for the first 12 hours, 24 hours, and 48 hours of intensive care unit admission. We analyzed their ability to predict mortality and GOSE by receiver operator characteristics. RESULTS: Mean age was 33.9 (range, 16-83) years, mean admission Glasgow Coma Scale score 6.4 +/- 3, and mean head Abbreviated Injury Scale score 4.2 +/- 0.72. The 30-day mortality rate was 13.3%. Of the 45 patients in whom GOSE at 12 months was available, 28 (62%) had good neurologic outcomes (GOSE score >4). Traditional markers of poor outcome (admission SBP, admission Glasgow Coma Scale, and Marshall score) were not different between groups with good or poor outcome. PTD, PTD/D, and %time SBP <110 mm Hg and SBP <120 mm Hg predicted mortality at 12 hours, 24 hours, and 48 hours (p < 0.04). Percent time SBP <110 mm Hg in the first 24 hours was predictive of 12-month GOSE (p = 0.02). PTD/D SBP <120 mm Hg in the first 24 hours and PTD and PTD/D in the first 48 hours were also predictive of 12-month GOSE (p < 0.05). CONCLUSIONS: Within the first 48 hours of intensive care unit admission, hypotension was found to be predictive of mortality and functional outcomes at higher thresholds than traditionally defined. Systemic blood pressure targets closer to 120 mm Hg may be more efficacious in minimizing secondary insults and particularly useful in settings without invasive intracranial monitoring capabilities. LEVEL OF EVIDENCE: III, prognostic study. PMID- 22673238 TI - Systemic inflammation worsens outcomes in emergency surgical patients. AB - BACKGROUND: Acute care surgeons are uniquely aware of the importance of systemic inflammatory response and its influence on postoperative outcomes; concepts like damage control have evolved from this experience. For surgeons whose practice is mostly elective, the significance of such systemic inflammation may be underappreciated. This study sought to determine the influence of preoperative systemic inflammation on postoperative outcome in patients requiring emergent colon surgery. METHODS: Emergent colorectal operations were identified in the American College of Surgeons National Surgical Quality Improvement Program 2008 dataset. Four groups were defined by the presence and magnitude of the inflammatory response before operation: no inflammation, systemic inflammatory response syndrome (SIRS), sepsis, or severe sepsis/septic shock. Thirty-day survival was analyzed by Kaplan-Meier method. RESULTS: A total of 3,305 patients were identified. Thirty-day survival was significantly different (p < 0.0001) among the four groups; increasing magnitudes of preoperative inflammation had increasing probability of mortality (p < 0.0001). Hazard ratios indicated that, compared with patients without preoperative systemic inflammation, the relative risk of death from SIRS was 1.9 (p < 0.0001), from sepsis was 2.5 (p < 0.0001), and from severe sepsis/septic shock was 6.7 (p < 0.0001). Operative time of <150 minutes was associated with decreased risk of morbidity (odds ratio = 0.64; p < 0.0001). CONCLUSIONS: Upregulation of the systemic inflammatory response is the primary contributor to death in emergency surgical patients. In SIRS or sepsis patients, operations <2.5 hours are associated with fewer postoperative complications. These results further reinforce the concept of timely surgical intervention and suggest a potential role for damage control operations in emergency general surgery. LEVEL OF EVIDENCE: II, prognostic study. PMID- 22673239 TI - Recombinant human soluble thrombomodulin improves mortality and respiratory dysfunction in patients with severe sepsis. AB - BACKGROUND: Respiratory dysfunction associated with severe sepsis is a serious condition leading to poor prognosis. Activation of coagulation is a consequence of and contributor to ongoing lung injury in severe sepsis. The purpose of this study was to examine the efficacy of recombinant human soluble thrombomodulin (rhTM), a novel anticoagulant agent, for treating patients with sepsis-induced disseminated intravascular coagulation (DIC) in terms of mortality and respiratory dysfunction. METHODS: This study comprised 86 consecutive patients with sepsis-induced DIC who required ventilator management. The initial 45 patients were treated without rhTM (control group), and the following 41 patients were given rhTM (0.06 mg/kg/d) for 6 days (rhTM group). Patients were followed up for 90 days after study entry. Sequential Organ Failure Assessment (SOFA) score and lung injury score were recorded until 7 days after entry. RESULTS: The baseline characteristic of severity of illness was significantly higher in the rhTM group than in the control group. Nevertheless, 90-day mortality rate in the rhTM group was significantly lower than that in the control group (37% vs. 58%, p = 0.038). There was a significant difference in the serial change of SOFA score from baseline to day 7 between the two groups (p = 0.009). Both the respiratory component of the SOFA score and the lung injury score in the rhTM group were significantly lower compared with the control group (p = 0.034 and p < 0.001, respectively). CONCLUSIONS: rhTM may have a significant beneficial effect on mortality and respiratory dysfunction in patients with sepsis-induced DIC. LEVEL OF EVIDENCE: III, therapeutic study. PMID- 22673240 TI - Focused rapid echocardiographic evaluation versus vascular cather-based assessment of cardiac output and function in critically ill trauma patients. AB - BACKGROUND: Focused rapid echocardiographic evaluation (FREE) is a comprehensive transthoracic echocardiogram tailored for the intensive care unit. It assesses both the cardiac index (CI) and left ventricular ejection fraction (EF). FREE and vascular catheter-derived CI was compared, and the ability of CI to detect moderate to severe dysfunction (EF <40%) was determined. METHODS: FREE quality assurance database was reviewed to identify patients who had a hemodynamic catheter. RESULTS: Of 507 FREEs, 115 patients were identified, 25 pulmonary artery catheters (PACs) and 90 FloTrac Vigileo (FT/V) arterial catheters. There were 27 patients with an EF <40%. In 86%, the CI was determined by FREE, and it changed care in 59%. The CI correlation for FREE versus PAC was r = 0.88 and versus FT/V was r = 0.63 (p < 0.05). The PAC-FREE bias was -0.07 (95% confidence interval -0.89 to 0.74) and the FT/V-FREE bias was -0.13 (95% confidence interval -1.4 to 1.1). FREE-PAC categorized patients the same way 87% and FREE-FT/V 76%; in patients with EF <40%, this changed to 90% and 63%, respectively. Using a threshold value (CI <= 2.5), the PAC detected dysfunction in 62.5% and the F/VT in 6%, p < 0.05. CONCLUSIONS: There was excellent agreement between FREE and PAC but less with FT/V, especially in patients with and EF <40%. FREE can be used to validate catheter-derived data and provide important additional information. Further studies are needed to determine its impact on patient outcome. LEVEL OF EVIDENCE: III, diagnostic study. PMID- 22673242 TI - Risk factors for central line-associated bloodstream infections in the era of best practice. AB - BACKGROUND: Best clinical practice aims to eliminate central line-associated blood stream infections (CLABSIs). However, CLABSIs still occur. This study's aim was to identify risk factors for CLABSI in the era of best practice. METHODS: Critically ill surgical patients admitted over 2 years to the intensive care unit (ICU) for >= 4 days were studied. Patients with CLABSI as cause for ICU admission were excluded. Patients who developed CLABSI (National Healthcare Safety Network definition) were compared with those who did not. Hand hygiene, maximal sterile barriers, chlorhexidine scrub, avoidance of femoral vein, and proper maintenance were emphasized. Variables collected included demographics, diagnosis, and severity of illness using the Acute Physiology and Chronic Health Evaluation (APACHE) IV database and the hospital central data repository. RESULTS: Of 961 patients studied, 51 patients (5.2%) developed 59 CLABSIs. Mean time from ICU admission to CLABSI was 26 days +/- 26 days. The CLABSI group was more likely to be male (odds ratio [OR] 1.93, 95% confidence interval [CI] 1.02-3.68), more critically ill on ICU admission (APACHE IV score 85.2 +/- 21.9 vs. 65.6 +/- 23.2, p < 0.01), more likely admitted to the emergency surgery service (OR 1.92, 95% CI 1.02-3.61), and had an association with reopening of recent laparotomy (OR 2.08, 95% CI 1.10-3.94). CONCLUSION: In the era of best practice, patients who develop CLABSI are clinically distinct from those who do not develop CLABSI. These CLABSIs may be due to deficiencies of the CLABSI definition or represent patient populations requiring enhanced prevention techniques. LEVEL OF EVIDENCE: III, prognostic study. PMID- 22673241 TI - Ventilator-associated pneumonia rates at major trauma centers compared with a national benchmark: a multi-institutional study of the AAST. AB - BACKGROUND: Ventilator-associated pneumonia (VAP) rates reported by the National Healthcare Safety Network (NHSN) are used as a benchmark and quality measure, yet different rates are reported from many trauma centers. This multi-institutional study was undertaken to elucidate VAP rates at major trauma centers. METHODS: VAP rate/1,000 ventilator days, diagnostic methods, institutional, and aggregate patient data were collected retrospectively from a convenience sample of trauma centers for 2008 and 2009 and analyzed with descriptive statistics. RESULTS: At 47 participating Level I and II centers, the pooled mean VAP rate was 17.2 versus 8.1 for NHSN (2006-2008). Hospitals' rates were highly variable (range, 1.8 57.6), with 72.3% being above NHSN's mean. Rates differed based on who determined the rate (trauma service, 27.5; infection control or quality or epidemiology, 11.9; or collaborative effort, 19.9) and the frequency with which VAP was excluded based on aspiration or diagnosis before hospital day 5. In 2008 and 2009, blunt trauma patients had higher VAP rates (17.3 and 17.6, respectively) than penetrating patients (11.0 and 10.9, respectively). More centers used a clinical diagnostic strategy (57%) than a bacteriologic strategy (43%). Patients with VAP had a mean Injury Severity Score of 28.7, mean Intensive Care Unit length of stay of 20.8 days, and a 12.2% mortality rate. 50.5% of VAP patients had a traumatic brain injury. CONCLUSIONS: VAP rates at major trauma centers are markedly higher than those reported by NHSN and vary significantly among centers. Available data are insufficient to set benchmarks, because it is questionable whether any one data set is truly representative of most trauma centers. Application of a single benchmark to all centers may be inappropriate, and reliable diagnostic and reporting standards are needed. Prospective analysis of a larger data set is warranted, with attention to injury severity, risk factors specific to trauma patients, diagnostic method used, VAP definitions and exclusions, and reporting guidelines. LEVEL OF EVIDENCE: III, prognostic study. PMID- 22673243 TI - Long-term survival after major trauma in geriatric trauma patients: the glass is half full. AB - BACKGROUND: The objective is to examine the long-term survival status of geriatric trauma patients (GTPs) after major trauma. METHODS: A 10-year retrospective review at a Level I trauma center was performed. GTP were defined as age >= 65 years, with Injury Severity Score >= 30. Primary endpoints: survival at hospital discharge and long-term survival and discharge status. Two groups were defined: Abbreviated Injury Score (AIS) head >3 (G1, n = 116) and AIS head <= 3 (G2, n = 29). For GTP surviving hospitalization, two subgroups were defined: AIS head >3 (SG1, n = 77) and AIS head <= 3 (SG2, n = 20). Comparisons were analyzed for exploratory purposes only by independent t-tests or Mann-Whitney rank sums tests as appropriate. Long-term survival was plotted by a Kaplan-Meier curve. RESULTS: A total of 145 GTP met inclusion criteria. In-hospital mortality was 33%. Nonsurvivors had lower Glasgow Coma Scale score (6 vs. 14, p < 0.001), higher Injury Severity Score (38 vs. 34, p < 0.003), and lower Revised Trauma Score (5.97 vs. 7.84, p < 0.002). Hospital mortality for G1 was 34% (39 of 116) and for G2 was 31% (9 of 29). In group 1 (n = 116), 39 patients (34%) died while 77 (66%) survived a median of 29 months (interquartile range [IQR] = 6-62). In group 2 (n = 29), 9 patients (31%) died while 20 (69%) survived a median of 46.50 months (IQR = 26.75-79). For the 77 patients who were alive at discharge (subgroup 1, AIS >3), 25 (32%) died while 52 (68%) survived a median of 33 months (IQR = 10.50-72.75). For the 20 patients with AIS <= 3 (subgroup 2), 7 of 20 (35%) died while 13 (65%) survived a median of 49 months (IQR = 30.50-93.50). A total of 28 patients (19%) survived more than 5 years from the time of discharge. For these 65 GTPs who are currently alive at the time of follow-up, living status could be determined for 49 (75%) and 33 of 49 (67%) were living at home. CONCLUSIONS: This study documents appreciable long-term survival for GTP with major injury including severe head injury. A substantial proportion of these patients was able to return home. LEVEL OF EVIDENCE: III, prognostic/epidemiological study. PMID- 22673244 TI - Withdrawal of care: a 10-year perspective at a Level I trauma center. AB - BACKGROUND: Withdrawal or limitation of care (WLC) in trauma patients has not been well studied. We reviewed 10 years of deaths at our adult Level I trauma center to identify the patients undergoing WLC and to describe the process of trauma surgeon-managed WLC. METHODS: This is a retrospective review of WLC. Each patient was assigned to one of three modes of WLC: care withdrawn, limited or no resuscitation, or organ harvest. Frequency, timing, and circumstances of WLC, including family involvement, ethics committee consultation, palliative care, and hospice, were reviewed. RESULTS: From 2000 through 2009, 375 patients died with WLC (54% of all deaths; 93% at >= 24 hours). For age >= 65 years, 80% were WLC. Overall, 15% had advance directive documents. Traumatic brain or high cervical spine injury was the cause of death in 63%. Factors associated with WLC included age, comorbidities, injury mechanism and severity, and nontrauma activation status. At time of death, 316 (84%) WLC were under trauma surgeon management. In this group, mode of WLC was care withdrawn in 74%, organ harvest in 20%, and limited or no resuscitation in 6%. Rationale for WLC in non-organ harvest patients was poor neurologic prognosis in 86% and futility in 76%. When family was identified, end-of-life discussions with physicians occurred in 100%. Conflicts over WLC occurred in 6.6% and were not associated with any demographic group. Ethics committee was involved in 2.8%. For care-withdrawn patients, median time to death from first WLC order was 6.6 hours. Palliative care and hospice consults (6% and 9%) increased yearly. CONCLUSIONS: WLC occurred in over 50% of all trauma deaths and exceeded 90% at >= 24 hours. Hospice and palliative care were increasingly important adjuncts to WLC. Guidelines for WLC should be developed to ensure quality end-of-life care for trauma patients in whom further care is futile. LEVEL OF EVIDENCE: III, therapeutic study. PMID- 22673245 TI - Remote inflammatory response in liver is dependent on the segmental level of spinal cord injury. AB - BACKGROUND: Traumatic spinal cord injury (SCI) triggers a systemic inflammatory response (SIR) that contributes to a high incidence of secondary organ complications, particularly after a cervical or high-level thoracic injury. Because liver plays a key role in initiating and propagating the SIR, the aim of this study was to assess the effects that SCI at differing segmental levels has on the intensity of the inflammatory response in the liver. METHODS: Using male Wistar rats, clip compression SCI was performed at the 4th thoracic (T4 SCI; high level SCI) or the 12th thoracic (T12 SCI; low-level SCI) spinal cord segment. Sham-injured rats had a partial laminectomy, but no SCI. Leukocyte recruitment to the liver, hepatic blood flow, and hepatocellular injury/death were assessed using intravital microscopy and histology. Chemokine and cytokine concentrations were assessed in the liver. Outcomes were measured at 1.5 hours, 12 hours, and 24 hours after SCI. RESULTS: At 12 hours after injury, T4 SCI caused a threefold increase in hepatic leukocyte recruitment compared with T12 SCI (p < 0.05). T4 SCI induced 50% more hepatocyte injury than T12 SCI at 12 hours (p < 0.05). Hepatic blood flow decreased after SCI, but not after sham injury, and stayed decreased only after T4 SCI at 24 hours after injury. The T4 SCI-induced changes were accompanied by increases in the hepatic concentrations of interleukin-1beta, leptin, interleukin 10, and cytokine-induced neutrophil chemoattractant-1 at 1.5 hours. CONCLUSIONS: Our findings indicate that traumatic SCI triggers an acute SIR that contributes to hepatocellular injury. SCI-induced remote injury/dysfunction to the liver appears to be transient and is more robust after an upper thoracic SCI compared with a lower thoracic SCI. PMID- 22673246 TI - The severity of brain damage determines bone marrow stromal cell therapy efficacy in a traumatic brain injury model. AB - BACKGROUND: Patients who survive traumatic brain injury (TBI) can undergo serious sensorial and motor function deficits. Once damage occurs, there is no effective treatment to bring patients to full recovery. Recent studies, however, show bone marrow stromal cells (BMSC) as a potential therapy for TBI. METHODS: This study was designed to determine whether the degree of neurologic deficits influences the efficacy of cell therapy using intracerebral transplantation of BMSC in an experimental model of chronically established TBI. Adult Wistar rats were subjected to weight-drop impact causing TBI. Two months later, the animals were classified according to levels of neurologic deficits. To achieve this, we used two different functional tests: the modified Neurologic Severity Score test and internal zone Permanence Time in Video-Tracking-Box analysis. Saline only or saline containing BMSC was injected into injured brain tissue of the animals that were classified having moderate or severe neurologic damage depending on the level of established functional deficits. All experimental groups were evaluated in the course of the following 2 months to study the efficacy of BMSC administration. The animals were then killed and their brains were studied. RESULTS: Our results showed that significant functional improvement was seen when BMSC was injected into animals with moderate brain damage, but no significant improvement was found in animals with severe functional deficits when compared with controls. CONCLUSION: These findings suggest that the severity of neurologic damage may determine the potential effect of cell therapy when applied to chronically established TBI. PMID- 22673247 TI - Infusion of 4 degrees C normal saline can improve the neurological outcome in a porcine model of cardiac arrest. AB - BACKGROUND: This study sought to investigate induction of therapeutic hypothermia using ice-cold intravenous fluid after cardiopulmonary resuscitation (CPR). The effects on temperature, hemodynamics, cognitive performance and the accompanying neurohistopathological changes, and apoptosis were assessed. METHODS: Fourteen piglets had 4 minutes of untreated ventricular fibrillation, followed by CPR. The animals in which spontaneous circulation was restored were randomly assigned to two groups: the hypothermia group (n = 7) was given an infusion of 4 degrees C cold normal saline solution 30 mL/kg at an infusion rate of 1.33 mL/kg/min, followed by 10 mL/kg/h to 4 hours after restoration of spontaneous circulation; the control group (n = 7) was given the same infusion at room temperature. Variables were measured repeatedly until 4 hours after restoration of spontaneous circulation. Neurocognitive performance was evaluated 24 hours after CPR. Then animals were killed and the brains were removed for histopathology at 24 hours after restoration of spontaneous circulation. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling method was used for apoptosis evaluation. RESULTS: Compared with the control group, the core temperature of the hypothermia group was significantly decreased (p < 0.01). The cerebral performance categories at 24 hours after restoration of spontaneous circulation in the hypothermia group were better than that in the control group (p < 0.05). The percentage of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling-positive cells in the cortex and dentate gyrus of the hippocampus were significantly reduced in the hypothermia group compared with the control group at 24 hours after restoration of spontaneous circulation. By observation of transmission electron microscopy, the neuron damages were significantly reduced in hypothermia group. CONCLUSION: 4 degrees C normal saline solution is a safe and effective method to reduce brain damages and prevent apoptotic cell death after cardiac arrest. PMID- 22673248 TI - Attenuating brain edema, hippocampal oxidative stress, and cognitive dysfunction in rats using hyperbaric oxygen preconditioning during simulated high-altitude exposure. AB - BACKGROUND: We assessed whether hyperbaric oxygen preconditioning (HBO2P) in rats induced heat shock protein (HSP)-70 and whether HSP-70 antibody (Ab) preconditioning attenuates high altitude exposure (HAE)-induced brain edema, hippocampal oxidative stress, and cognitive dysfunction. METHODS: Rats were randomly divided into five groups: the non-HBO2P + non-HAE group, the HBO2P + non HAE group, the non-HBO2P + HAE group, the HBO2P + HAE group, and the HBO2P + HSP 70 Abs + HAE group. The HBO2P groups were given 100% O2 at 2.0 absolute atmospheres for 1 hour per day for 5 consecutive days. The HAE groups were exposed to simulated HAE (9.7% O2 at 0.47 absolute atmospheres of 6,000 m) in a hypobaric chamber for 3 days. Polyclonal rabbit anti-mouse HSP-70-neutralizing Abs were intravenously injected 24 hours before the HAE experiments. Immediately after returning to normal atmosphere, the rats were given cognitive performance tests, overdosed with a general anesthetic, and then their brains were excised en bloc for water content measurements and biochemical evaluation and analysis. RESULTS: Non-HBO2P group rats displayed cognitive deficits, brain edema, and hippocampal oxidative stress (evidenced by increased toxic oxidizing radicals [e.g., nitric oxide metabolites and hydroxyl radicals], increased pro-oxidant enzymes [e.g., malondialdehyde and oxidized glutathione] but decreased antioxidant enzymes [e.g., reduced glutathione, glutathione peroxide, glutathione reductase, and superoxide dismutase]) in HAE. HBO2P induced HSP-70 overexpression in the hippocampus and significantly attenuated HAE-induced brain edema, cognitive deficits, and hippocampal oxidative stress. The beneficial effects of HBO2P were significantly reduced by HSP-70 Ab preconditioning. CONCLUSION: Our results suggest that high-altitude cerebral edema, cognitive deficit, and hippocampal oxidative stress can be prevented by HSP-70-mediated HBO2P in rats. PMID- 22673249 TI - Effectiveness of short-term 6-hour high-volume hemofiltration during refractory severe septic shock. AB - BACKGROUND: The effectiveness of a single 6-hour session of high-volume hemofiltration (HVHF) was evaluated in terms of decreased norepinephrine (NE) requirements, progressive refractory hypotension and hypoperfusion by the fourth hour, and observed versus expected hospital mortality in patients with refractory severe septic shock. METHODS: A prospective cohort study conducted at the intensive care unit with 31 patients suffering from severe septic shock (NE dose >= 0.3 MUg kg min to maintain mean arterial pressure 70-80 mm Hg and lactic acidosis) and refractory to treatments recommended by Surviving Sepsis Campaign, 2008. All patients were subjected to a single short-term 6-hour HVHF with a goal directed protocol. Changes in NE dose, hemodynamic, metabolic, and respiratory parameters were measured at the onset (t0), 4 (t4) and 6 hours (t6) during HVHF. Patients were considered responders if by t4 of HVHF, they showed a decrease in NE dose >= 50%, maintaining mean arterial pressure 80 mm Hg to 70 mm Hg. RESULTS: : Twenty-five of the 31 patients responded to HVHF treatment (responders), whereas 6 did not (nonresponders). In the responders group, a decrease in NE dose was observed by t4 (1.3 +/- 0.5 MUg kg min). This beneficial effect was maintained by t6 of treatment. Hemodynamic, metabolic, and respiratory parameters and other organic function indicators were also significantly improved by t4 and maintained by t6. Hospital mortality (45.16%) was significantly lower than that predicted by Sequential Organ Failure Assessment score (>90%): 83% for nonresponders versus 36% for responders. CONCLUSIONS: We conclude that a single session of short-term 6-hour HVHF in patients with refractory severe septic shock reduces NE dose requirements and improves organic function already by the fourth hour of treatment. LEVEL OF EVIDENCE: III, therapeutic study. PMID- 22673250 TI - Deciphering the use and predictive value of "emergency medical services provider judgment" in out-of-hospital trauma triage: a multisite, mixed methods assessment. AB - BACKGROUND: "Emergency medical services (EMS) provider judgment" was recently added as a field triage criterion to the national guidelines, yet its predictive value and real world application remain unclear. We examine the use and independent predictive value of EMS provider judgment in identifying seriously injured persons. METHODS: We analyzed a population-based retrospective cohort, supplemented by qualitative analysis, of injured children and adults evaluated and transported by 47 EMS agencies to 94 hospitals in five regions across the Western United States from 2006 to 2008. We used logistic regression models to evaluate the independent predictive value of EMS provider judgment for Injury Severity Score >= 16. EMS narratives were analyzed using qualitative methods to assess and compare common themes for each step in the triage algorithm, plus EMS provider judgment. RESULTS: 213,869 injured patients were evaluated and transported by EMS over the 3-year period, of whom 41,191 (19.3%) met at least one of the field triage criteria. EMS provider judgment was the most commonly used triage criterion (40.0% of all triage-positive patients; sole criterion in 21.4%). After accounting for other triage criteria and confounders, the adjusted odds ratio of Injury Severity Score >= 16 for EMS provider judgment was 1.23 (95% confidence interval, 1.03-1.47), although there was variability in predictive value across sites. Patients meeting EMS provider judgment had concerning clinical presentations qualitatively similar to those meeting mechanistic and other special considerations criteria. CONCLUSIONS: Among this multisite cohort of trauma patients, EMS provider judgment was the most commonly used field trauma triage criterion, independently associated with serious injury, and useful in identifying high-risk patients missed by other criteria. However, there was variability in predictive value between sites. PMID- 22673251 TI - Prehospital nausea and vomiting after trauma: Prevalence, risk factors, and development of a predictive scoring system. AB - BACKGROUND: Nausea and vomiting are common problems in trauma patients and potentially dangerous during trauma resuscitation. These symptoms are present in up to 10% of ambulance patients, but their prevalence in trauma patients is largely unknown. The aim of this study was to determine the prevalence of prehospital nausea and vomiting in trauma patients and evaluate antiemetic usage. METHODS: Prospective, cohort study of trauma resuscitation patients transported by ambulance to a major trauma centre. Patients with hemodynamic instability (systolic blood pressure <90, heart rate >120) or Glasgow Coma Scale score <14 on arrival were excluded. Nausea, vomiting, and antiemetic use were recorded. RESULTS: Convenience sample of 196 trauma resuscitation patients (68% men; age, 42 +/- 18 years, mean Injury Severity Score 8 +/- 7) were interviewed over the 5 month study period, of a total 369 admitted trauma patients (53%). Seventy-five (38%) patients reported some degree of nausea, 57 (29%) moderate or severe nausea, and 15 (8%) vomited. Older age and female gender were associated with vomiting (p < 0.01). Seventy-nine patients (40%) received a prophylactic antiemetic. Of these, four became nauseous (5%), compared with 71 of 117 (61%) for patients not given an antiemetic (p < 0.0001). CONCLUSIONS: Prehospital nausea and vomiting are more common in our cohort of trauma patients than the reported rates in the literature for nontrauma patients transported to hospital by ambulance. Only 40% of patients receive prophylactic antiemetics, but those patients are less likely to develop symptoms. LEVEL OF EVIDENCE: V, epidemiological study. PMID- 22673252 TI - Repeat imaging in trauma transfers: a retrospective analysis of computed tomography scans repeated upon arrival to a Level I trauma center. AB - BACKGROUND: The repetition of computed tomography (CT) imaging in caring for injured patients transferred between institutions is common, but it is not well studied. Our objective is to quantify and describe the characteristics associated with repeating chest and abdominal CT images for patients transferred to trauma centers and to determine whether repeat imaging leads to delays in definitive care or disparate outcomes. METHODS: This is a retrospective review of adult, blunt trauma patients transferred to two Level I trauma centers between January 2004 and May 2008 who underwent CT imaging of the chest, abdomen, or both. RESULTS: 60% of patients had at least one study repeated upon arrival to the trauma center. Variables associated with repeat imaging include Injury Severity Scores between 24 and 33 versus <15 (odds radio [OR], 1.6; 95% confidence interval [CI], 1.05-2.4), transfer to University of North Carolina (OR, 1.5; 95% CI, 1.01-2.2), transport by helicopter (OR, 1.6; 95% CI, 1.2-2.2), transfer in any year before 2008 (OR, 2.4; 95% CI, 1.6-3.6 for 2007; OR, 3.4; 95% CI, 2.2-5.3 for 2006; OR, 3.0; 95% CI, 1.8-5.0 for 2005; OR, 2.8; 95% CI, 1.7-4.7 for 2004), and triage alert level higher than the least severe level III (OR, 1.6; 95% CI, 1.01-2.7 for level II; OR, 2.2; 95% CI, 1.2-4.1 for level I). In adjusted models, there was no evidence that repeat imaging neither shortened the total time to definitive care nor altered patient outcomes. CONCLUSIONS: Injured patients often undergo imaging that gets repeated, adding cost and radiation exposure while not significantly altering outcomes. The current policy push to digitize medical records must include provisions for the interoperability and use of imaging software. LEVEL OF EVIDENCE: III, therapeutic study. PMID- 22673253 TI - Outcome of patients with severe brain trauma who were treated either by neurosurgeons or by trauma surgeons. AB - BACKGROUND: In Central Europe, patients with severe traumatic brain injury (TBI) are frequently treated by trauma surgeons rather than neurosurgeons. The objective of this study was to compare outcomes of patients with TBI by trauma surgeons or neurosurgeons. This study is a retrospective analysis of prospectively collected data. METHODS: Between January 2001 and December 2005, 10 centers enrolled 311 operatively treated patients with severe TBI and no significant other injuries into observational studies. Data on accident, treatment, and outcomes were collected. Using the Glasgow Outcome Scale, 1-year outcomes were classified as "favorable" (scores 5 and 4) or "unfavorable" (scores <4). Data from patients operated by trauma surgeons ("group T") were compared with those from patients operated by neurosurgeons ("group N") using univariate and multivariate statistics. The scores published by Hukkelhoven et al. were used to estimate expected rates of death and unfavorable outcomes. RESULTS: There were 191 patients in group N and 120 in group T. There were no significant differences regarding age, sex, and trauma mechanisms between the two groups. Patients from group N had significantly higher trauma severity. The observed versus expected hospital mortality ratio was 0.84 for group N and 0.97 for group T (p = 0.051). One-year outcome was better in group T (28% vs. 19% good recovery, 1.7% vs. 9.4% vegetative status; p = 0.017), whereas mortality was not different (43% in both groups). Multivariate analysis revealed that outcomes were influenced by age and severity of TBI, whereas surgical specialty and treatment factors had no effects. CONCLUSION: With respect to operatively treated patients with TBI, trauma surgeons and neurosurgeons achieve comparable results. LEVEL OF EVIDENCE: II. PMID- 22673254 TI - Protocol-directed versus physician-directed weaning from noninvasive ventilation: the impact in chronic obstructive pulmonary disease patients. AB - BACKGROUND: Noninvasive ventilation (NIV), a technique widely used in intensive care units (ICUs), eliminates the need for many patients in respiratory failure to undergo intubation. However, few articles have described how to wean patients from NIV. Herein, we put forward a protocol to be performed by respiratory therapists to wean patients from NIV. METHODS: A prospective, randomized, controlled trial was performed in a respiratory ICU of a teaching hospital. Respiratory therapists screened patients daily. In the protocol-directed weaning group, the weaning attempt was initiated according to the protocol. In the physician-directed weaning group, the weaning attempt was initiated according to physicians' orders. RESULTS: At randomization, patients in the two groups had similar clinical characteristics. A total of 73 patients were successfully weaned from NIV (37 in the protocol-directed group and 36 in the physician-directed group). The preponderance of them (64%) was chronic obstructive pulmonary disease patients. Compared with physician-directed weaning, protocol-directed weaning reduced the duration of NIV (4.4 +/- 2.5 days vs. 2.6 +/- 1.5 days, respectively, p < 0.001) and the duration of the ICU stay (8.1 +/- 5.5 days vs. 5.8 +/- 2.7 days, respectively, p = 0.02). In the protocol-directed group, the successful weaning rate was 57%, 27%, 13%, 0%, and 3% on the 1st, 2nd, 3rd, 4th, and 5th days after randomization, respectively. CONCLUSIONS: Protocol-directed weaning reduces the duration of NIV and the duration of the ICU stay. LEVEL OF EVIDENCE: II. PMID- 22673255 TI - Subglottic secretion drainage for preventing ventilator-associated pneumonia: an updated meta-analysis of randomized controlled trials. AB - BACKGROUND: Subglottic secretion drainage (SSD) has been shown to be associated with a lower incidence of ventilator-associated pneumonia (VAP) in a previous meta-analysis. However, a number of randomized controlled trials (RCTs) have been published since then, and so we aimed to conduct an updated meta-analysis. METHODS: A systematic literature search of Pubmed, Embase, and Cochrane Central Register of Controlled Trials was conducted using specific search terms. Eligible studies were RCTs that compared SSD with standard endotracheal tube care in mechanically ventilated adult patients. RESULTS: Ten RCTs with 2,213 patients were identified. SSD significantly reduced incidence of VAP (relative risk [RR] = 0.56, 95% confidence interval [CI]: 0.45-0.69, p < 0.00001) and early-onset VAP (RR = 0.23, 95% CI: 0.13-0.43, p < 0.00001), shortened ventilation duration by 1.55 days (95% CI: -2.40 to -0.71 days, p = 0.0003), and prolonged time to VAP by 3.90 days (95% CI: 2.56-5.24 days). Subgroup analyses suggested a significant reduction in incidence of VAP when stratified by intermittent (RR = 0.49, 95% CI: 0.34-0.71, p = 0.0001) and continuous SSD (RR = 0.61, 95% CI: 0.46-0.79, p = 0.0003). No significant differences were observed regarding incidence of late onset VAP, overall mortality, or length of intensive care unit or hospital stay. CONCLUSIONS: This updated meta-analysis confirmed that SSD was beneficial in preventing VAP. Furthermore, the effect of SSD on late-onset VAP, comparison between intermittent and continuous SSD, and safety of SSD in mechanically ventilated patients should be evaluated in future RCTs. LEVEL OF EVIDENCE: I, meta-analysis. PMID- 22673256 TI - Venous thromboembolism in the elderly: the result of comorbid conditions or a consequence of injury? AB - BACKGROUND: Venous thromboembolism (VTE) is a common complication in trauma patients. Several risk factors have been identified that may place patients at in increased risk for VTE including preexisting medical conditions, iatrogenic factors, and injury-related factors. Advanced age has also been implicated as a risk factor for VTE. The purpose of this study was to determine the incidence and outcomes of VTE in geriatric trauma patients as well as to identify risk factors for VTE in this population. METHODS: We performed a 10-year retrospective review of all trauma patients aged 65 years or older discharged with a diagnosis of VTE. Demographic data, injuries, mechanism, Injury Severity Score, Abbreviated Injury Score, Glasgow Coma Scale, length of stay, and mortality were collected. RESULTS: : Of 2,521 trauma patients aged 65 years or older, 82 (3.2%) were diagnosed with VTE. Seventy-two of 82 patients were diagnosed with deep vein thrombosis, and pulmonary embolism was found in 8 patients. Two patients had both a deep vein thrombosis and pulmonary embolism. Independent predictors of VTE included traumatic brain injury (p < 0.05); chest Abbreviated Injury Score >= 3 (p < 0.001); mechanical ventilation (p < 0.001); major operation (p < 0.001); and history of VTE (p = 0.05). Other comorbid conditions were not significantly associated with VTE. Preinjury anticoagulation had a trend toward a protective effect. Although length of stay was longer in patients with VTE (adjusted mean difference 14.7 days, p < 0.001), mortality for patients with and without VTE was 8.5% and 7.0%, respectively (p = 0.59). CONCLUSION: VTE is associated with prolonged length of stay and duration of mechanical ventilation as well as continued medical dependence after discharge. Several risk factors place the elderly trauma patient at an increased risk for VTE, and trauma or injury-related risk factors seem to have a greater impact on the development of VTE in comparison to underlying conditions or increasing patient age (>65 years). LEVEL OF EVIDENCE: II, prognostic study. PMID- 22673257 TI - Effectiveness of clinical guidelines for deep vein thrombosis prophylaxis in reducing the incidence of venous thromboembolism in critically ill children after trauma. AB - BACKGROUND: Historically, 6% of critically ill children developed clinically apparent venous thromboembolism (VTE) after trauma at our Level I pediatric trauma center. We hypothesized that implementation of clinical guidelines for thrombosis prophylaxis incorporating both VTE risk and bleeding risk would reduce VTE incidence without increased bleeding. METHODS: VTE, both clinically apparent and those only detected by guideline-directed screening, were prospectively identified for all children admitted to the intensive care unit after trauma during three time periods: preimplementation of guidelines for VTE thromboprophylaxis (PRE; April 1, 2006-June 30, 2007), the intervening period (ROLL OUT; July 1, 2007-November 4, 2008), and postguideline implementation (POST; November 5, 2008-June 1, 2010). For patients classified as high risk for VTE, anticoagulation was recommended. For those patients at high risk of VTE with high risk of bleeding, anticoagulation was deferred and screening ultrasound performed. RESULTS: Fourteen of 546 subjects developed VTE. There was a decrease in total VTE (p = 0.041) and clinical VTE (p = 0.001) after guideline implementation. The nine VTE PRE (5.2%) were clinically symptomatic, while the three VTE POST (1.8%) were detected by guideline-directed screening ultrasound. Implementation of guidelines did not increase overall thromboprophylaxis, with decreased anticoagulation in patients at low risk of VTE. No bleeding complications occurred. No patients classified by the guidelines as low risk for VTE developed VTE. CONCLUSION: The incidence of clinical VTE and total VTE decreased after implementation of clinical guidelines for thromboprophylaxis in critically ill children after trauma. This decrease in VTE was not associated with increased prophylactic anticoagulation nor increased bleeding. The guidelines were predictive in identifying patients at low risk for VTE. LEVEL OF EVIDENCE: II, therapeutic study. PMID- 22673258 TI - Quality indicators used by trauma centers for performance measurement. AB - BACKGROUND: To describe the quality indicators (QIs) that trauma centers use for quality measurement and performance improvement. Measuring and reporting quality of care is a critical step to improve the quality of care. QIs compare actual trauma care against ideal criteria and identify patients in whom care may have been suboptimal and should be further reviewed. METHODS: Three hundred thirty verified trauma centers in the United States, Canada, Australia, and New Zealand had their websites reviewed and leadership surveyed regarding QI use. The indicators identified were classified according to definition specifications, phase of care, Institute of Medicine aims, and contents. RESULTS: Two hundred fifty-one centers responded to the survey (76%) and the majority (97%) indicated that they use QIs. We obtained 10,587 QIs from 262 centers (survey responses and website review) of which 1,102 were unique indicators. The QIs primarily assessed the safety (49%), effectiveness (32%), efficiency (27%), and timeliness (22%) of hospital processes (64%) and outcomes (24%). The majority of indicators were used by a small number of centers (551 of 1,102 unique indicators used by single centers). CONCLUSION: Our study provides the first description of the QIs used by verified trauma centers in four high-income countries with similar systems of trauma care. The majority of trauma centers measure QIs designed to examine the safety, effectiveness, efficiency, and timeliness of hospital processes and outcomes. Opportunities exist to standardize existing QIs to allow broader implementation and develop new QIs to examine patient-centered care and equality of care. PMID- 22673259 TI - Effect of seat belt pretensioners on human abdomen and thorax: Biomechanical response and risk of injuries. AB - BACKGROUND: A better coupling of the occupant to the car seat in the early phase of a frontal or far side impacts using pretensioner systems may reduce the likelihood of the submarining effect or increases the likelihood of seat belt engaging the shoulder, respectively. However, the high belt forces may also increase the risk of upper body injuries to the vehicle occupant (especially in abdominal region). It was hypothesized that human body characteristics, such as body mass index (BMI) influence the biomechanical response and injury outcome to the abdominal regions during static pretensioning deployment tests. METHODS: Four postmortem human specimens (PMHS), in a BMI range from 15.6 to 31.2, were positioned in production seats in a normal passenger position and were restrained using a standard three-point belt system. The pretension forces in the belts were generated at two points (retractor and right anchorage) or at all three locations (retractor, left anchorage, and right anchorage). An optical motion capture system and acceleration cubes mounted to the lumbar spine were used to measure the abdomen deformation during testing. RESULTS: The normalized deflections of the thorax recorded at the level of fourth rib were under 10% (noninjury level). Two different patterns were observed in the time histories of abdominal penetration rate in the four PMHSs associated with lower and higher BMI. Abdominal injuries (spleen lacerations) were observed only in the two PMHS with highest BMI. CONCLUSION: Based on data from this study and similar data from the literature, belt velocity and FmaxCmax were shown to be the best injury predictors for injury risk analysis for Abbreviated Injury Scale 2+ and for Abbreviated Injury Scale 3+ injuries, respectively. PMID- 22673260 TI - Patient satisfaction with surgeons in a trauma population: testing a structural equation model using perceptions of interpersonal and technical care. AB - BACKGROUND: Research has shown that interpersonal care is positively associated with patient satisfaction. The literature is not as clear concerning patient perceptions of technical care. Evaluating patient satisfaction requires understanding the influence of patient perceptions of interpersonal and technical aspects of care. METHODS: This prospective, cross-sectional telephone survey examined the relationship between patient satisfaction, interpersonal care, and technical care. Respondents were asked to recall the trauma surgeon and then rate them for satisfaction with interpersonal and technical care. Patients were also asked to rate their global satisfaction (GS) with the healthcare. RESULTS: Structural equation modeling indicated that there was a significant direct effect of Interpersonal Care on Technical Care and Technical Care and Interpersonal Care on GS. Interpersonal care also had an indirect effect on GS though Technical Care. Fit indices showed that the hypothesized paths significantly improved the model. CONCLUSIONS: There were strong positive relationships between patient's perceptions of interpersonal care and technical care and GS. Patients that are unacquainted with technical aspects of care may make judgments based on satisfaction with interpersonal aspects of care. It is important that surgeons, even in a trauma environment, are aware of the strong relationship between patients' perceptions of interpersonal and technical care. Making efforts to focus on relationship-centered care will improve both personal and institutional satisfaction ratings. LEVEL OF EVIDENCE: III, epidemiological study. PMID- 22673261 TI - A web-based model to support patient-to-hospital allocation in mass casualty incidents. AB - BACKGROUND: In a mass casualty situation, evacuation of severely injured patients to the appropriate health care facility is of critical importance. The prehospital stage of a mass casualty incident (MCI) is typically chaotic, characterized by dynamic changes and severe time constraints. As a result, those involved in the prehospital evacuation process must be able to make crucial decisions in real time. This article presents a model intended to assist in the management of MCIs. The Mass Casualty Patient Allocation Model has been designed to facilitate effective evacuation by providing key information about nearby hospitals, including driving times and real-time bed capacity. These data will enable paramedics to make informed decisions in support of timely and appropriate patient allocation during MCIs. The model also enables simulation exercises for disaster preparedness and first response training. METHODS: Road network and hospital location data were used to precalculate road travel times from all locations in Metro Vancouver to all Level I to III trauma hospitals. Hospital capacity data were obtained from hospitals and were updated by tracking patient evacuation from the MCI locations. In combination, these data were used to construct a sophisticated web-based simulation model for use by emergency response personnel. RESULTS: The model provides information critical to the decision-making process within a matter of seconds. This includes driving times to the nearest hospitals, the trauma service level of each hospital, the location of hospitals in relation to the incident, and up-to-date hospital capacity. CONCLUSION: The dynamic and evolving nature of MCIs requires that decisions regarding prehospital management be made under extreme time pressure. This model provides tools for these decisions to be made in an informed fashion with continuously updated hospital capacity information. In addition, it permits complex MCI simulation for response and preparedness training. PMID- 22673262 TI - Mortality pattern of the 26/11 Mumbai terror attacks. AB - BACKGROUND: Mumbai, one of the industrial capitals cities of the world, has witnessed a series of terror attacks over the last two decades. The 2008 Mumbai terror attacks referred as "26/11" drew widespread global condemnation and killed 166 people, in addition to wounding more than 300 people. The mortality pattern and the pathophysiology of organ injuries are presented. The objective of this study was to determine the different patterns of injury in a terrorist attack of such magnitude and clinical implications in reducing mortality. METHODS: Data were collected from hospital records of 114 victims whose postmortems were conducted at the Sir JJ Group of Hospitals. The records were studied with respect to pattern and nature of injury. RESULTS: A total of 175 people were killed, 9 were terrorist with 166 victims. Of the 166 mortalities, postmortems were conducted on 114 predominately male victims ages 5 to 70 years old; 108 of these were dead on arrival. Sixty-eight people died from bullet injuries, 30 from blast injuries, and 10 had both bullet and blast injuries. Six were postoperative deaths (all bullet injuries), of which two were early postoperative deaths and four late postoperative deaths due to septicemia. CONCLUSION: There was multimodal pattern of injuries with predominance of bullet injuries sustained to vital organs. The hostage crisis resulted in varied and delayed evacuation times, which led to the death of nine victims with non-severe organ injuries. Delayed implementation of Prehospital Trauma Life Support due to the unsecured site and the hostage crisis can also be one of the causes. LEVEL OF EVIDENCE: V, epidemiological study. PMID- 22673264 TI - The first 72 hours of brain tissue oxygenation predicts patient survival with traumatic brain injury. AB - BACKGROUND: Utilization of brain tissue oxygenation (pBtO(2)) is an important but controversial variable in the treatment of traumatic brain injury. We hypothesize that pBtO(2) values over the first 72 hours of monitoring are predictive of mortality. METHODS: Consecutive, adult patients with severe traumatic brain injury and pBtO(2) monitors were retrospectively identified. Time-indexed measurements of pBtO(2), cerebral perfusion pressure (CPP), and intracranial pressure (ICP) were collected, and average values over 4-hour blocks were determined. Patients were stratified according to survival, and repeated measures analysis of variance was used to compare pBtO(2), CPP, and ICP. The pBtO(2) threshold most predictive for survival was determined. RESULTS: There were 8,759 time-indexed data points in 32 patients. The mean age was 39 years +/- 16.5 years, injury severity score was 27.7 +/- 10.7, and Glasgow Coma Scale score was 6.6 +/- 3.4. Survival was 68%. Survivors consistently demonstrated higher pBtO(2) values compared with nonsurvivors including age as a covariate (F = 12.898, p < 0.001). Individual pBtO(2) was higher at the time points 8 hours, 12 hours, 20 hours to 44 hours, 52 hours to 60 hours, and 72 hours of monitoring (p < 0.05). There was no difference in ICP (F = 1.690, p = 0.204) and CPP (F = 0.764, p = 0.389) values between survivors and nonsurvivors including age as a covariate. Classification and regression tree analysis identified 29 mm Hg as the threshold at which pBtO(2) was most predictive for mortality. CONCLUSION: The first 72 hours of pBtO(2) neurologic monitoring predicts mortality. When the pBtO(2) monitor remains below 29 mm Hg in the first 72 hours of monitoring, mortality is increased. This study challenges the brain oxygenation threshold of 20 mm Hg that has been used conventionally and delineates a time for monitoring pBtO(2) that is predictive of outcome. LEVEL OF EVIDENCE: III, prognostic study. PMID- 22673263 TI - Serum levels of ubiquitin C-terminal hydrolase distinguish mild traumatic brain injury from trauma controls and are elevated in mild and moderate traumatic brain injury patients with intracranial lesions and neurosurgical intervention. AB - BACKGROUND: This study compared early serum levels of ubiquitin C-terminal hydrolase (UCH-L1) from patients with mild and moderate traumatic brain injury (TBI) with uninjured and injured controls and examined their association with traumatic intracranial lesions on computed tomography (CT) scan (CT positive) and the need for neurosurgical intervention (NSI). METHODS: This prospective cohort study enrolled adult patients presenting to three tertiary care Level I trauma centers after blunt head trauma with loss of consciousness, amnesia, or disorientation and a Glasgow Coma Scale (GCS) score 9 to 15. Control groups included normal uninjured controls and nonhead injured trauma controls presenting to the emergency department with orthopedic injuries or motor vehicle crash without TBI. Blood samples were obtained in all trauma patients within 4 hours of injury and measured by enzyme-linked immunosorbent assay for UCH-L1 (ng/mL +/- standard error of the mean). RESULTS: There were 295 patients enrolled, 96 TBI patients (86 with GCS score 13-15 and 10 with GCS score 9-12), and 199 controls (176 uninjured, 16 motor vehicle crash controls, and 7 orthopedic controls). The AUC for distinguishing TBI from uninjured controls was 0.87 (95% confidence interval [CI], 0.82-0.92) and for distinguishing those TBIs with GCS score 15 from controls was AUC 0.87 (95% CI, 0.81-0.93). Mean UCH-L1 levels in patients with CT negative versus CT positive were 0.620 (+/- 0.254) and 1.618 (+/- 0.474), respectively (p < 0.001), and the AUC was 0.73 (95% CI, 0.62-0.84). For patients without and with NSI, levels were 0.627 (0.218) versus 2.568 (0.854; p < 0.001), and the AUC was 0.85 (95% CI, 0.76-0.94). CONCLUSION: UCH-L1 is detectable in serum within an hour of injury and is associated with measures of injury severity including the GCS score, CT lesions, and NSI. Further study is required to validate these findings before clinical application. LEVEL OF EVIDENCE: II, prognostic study. PMID- 22673265 TI - The therapeutic efficacy of endoscopic optic nerve decompression and its effects on the prognoses of 96 cases of traumatic optic neuropathy. AB - BACKGROUND: Traumatic optic neuropathy (TON) is an important cause of severe loss of vision due to blunt or penetrating head trauma. The pathogenesis of TON remains unclear, and there are several potential causes for the observed loss in vision. Endoscopic optic nerve decompression (EOND) has been reported to improve the visual prognosis in TON cases, but its efficacy remains controversial. It is important to investigate the therapeutic efficacy of EOND in the treatment of TON and to evaluate the relevant prognostic factors. METHODS: A retrospective study was conducted to analyze the clinical characteristics and prognoses of 96 TON cases. The chi(2) test and multiple logistic regression analyses were used to evaluate potential prognostic factors. RESULTS: : The overall rate of EOND effectiveness was 40.6% (39 of 96). A significantly higher effective rate (83.3%) was observed for patients with light perception compared with those without light perception (26.4%, p < 0.05). Univariate and multiple logistic regression analyses identified three variables (no light perception, undergoing EOND 3 days after trauma, and hemorrhage within the ethmoid and/or sphenoid sinus) that were significantly associated with unrecovered visual acuity. Age, loss of consciousness, optic canal fracture, preoperative steroid megadose treatment, and optic nerve sheath incision were all factors that showed no significant correlation with therapeutic efficacy. However, patients with fractures in a single medial wall of the optic canal appeared to have better prognoses than patients with multiple fractures or those with a single fracture in a lateral wall. CONCLUSIONS: The overall therapeutic efficacy of EOND for the treatment of TON is far from satisfactory, especially for patients without light perception. The factors that impact TON prognoses are complex and may be interrelated. The indication for EOND must be individualized. LEVEL OF EVIDENCE: III, epidemiological study. PMID- 22673266 TI - Recreational helmet use as a predictor of noncranial injury. AB - BACKGROUND: The effect of helmet use in the prevention of head injury has been clearly shown. However, the relationship between helmet compliance and other bodily (noncranial) injury has not been explored, yet may have important impact on strategies for injury prevention. The purpose of this study was to examine helmet use in an injured population to evaluate its association with noncranial trauma. METHODS: All entries in the Canadian National Trauma Registry were surveyed from 2000 to 2004 and limited to injuries sustained in recreational sports associated with helmet use. RESULTS: Over the 5-year period, 2,205 injuries met inclusion criteria. Cycling-related injuries were most frequent (43.5%). Alcohol consumption correlated significantly with lack of helmet use. Nonhelmeted individuals suffered significantly more noncranial injuries (85% vs. 68%, p < 0.0001) and had twice as many severe head injuries (Glasgow Coma Scale score <= 8) (odds ratio [OR]: 2.13, 95% confidence interval [CI]: 1.35-3.37) or any abnormal Glasgow Coma Scale score (OR: 1.96, 95% CI: 1.55-2.47). While controlling for age, sex, or type of sport activity performed, multivariate regression confirmed a reduction in associated noncranial injuries when helmets were used (OR: 0.86, 95% CI: 0.83-0.89). CONCLUSIONS: Within an injured population from sports-related activities, helmet use is associated with fewer noncranial injuries of all types suggesting reduced overall risk of injury in this group. In addition, use of helmets is associated with less frequent and less severe head injury. Alcohol consumption is related to increased risk of injury and is more prevalent in injured individuals who abstain from helmet use. LEVEL OF EVIDENCE: III, prognostic study. PMID- 22673267 TI - Injury pattern, injury severity, and mortality in 33,495 hospital-admitted victims of motorized two-wheeled vehicle crashes in The Netherlands. AB - BACKGROUND: Road traffic accidents involving motorized two-wheeled vehicle (MTV) riders often result in severe morbidity and mortality. The aim of this nationwide study is to describe the influence of the type of motorized two-wheeled vehicle on the patient injury severity and mortality on hospitalization, after MTV accidents in The Netherlands. METHODS: Data from the Institute for Road Safety Research and the Hospital Trauma Databases were analyzed. All MTV crash victims admitted to Dutch hospitals from 1993 to 2008 were included. Logistic regression analysis was performed on sex, age, type of MTV, Injury Severity Score, and Abbreviated Injury Scale to calculate the relative risks of severe trauma and mortality for motor and light-moped riders according to the Mantel and Haenszel procedure (RRmh). RESULTS: Among 33,495 MTV crash victims, 10,607 were motorcyclists, 19,708 moped riders, and 3,180 light-moped riders. In the light moped rider group head injury, especially severe head injury was most common in light-moped riders, and the prevalence of severe trauma (17.1%) and mortality (4.2%) was highest, compared with motorcyclists and moped riders. In elderly crash victims (>55 years), the risk to sustain severe trauma was almost twofold higher in light-moped riders compared with moped riders (RRmh: 1.79). Young motorcyclists (<25 years) had highest chances of dying (RRmh: 1.64). CONCLUSION: Hospitalized light-moped riders show more severe head injuries, severe trauma, and higher mortality than moped riders and motorcyclists. Young motorcyclists and elderly light-moped riders are most vulnerable, with highest chances of severe trauma and mortality. Continuing improvement of the MTV safety is urgent. LEVEL OF EVIDENCE: II, epidemiological study. PMID- 22673268 TI - Use of glycated albumin to distinguish occult diabetes mellitus from stress induced hyperglycemia in Chinese orthopedic trauma patients. AB - BACKGROUND: Some nondiabetic trauma patients with hyperglycemia have been found to have occult diabetes mellitus (ODM). We studied whether glycated albumin (GA) was an effective tool for detecting ODM in orthopedic trauma patients with elevated glucose levels. METHODS: A cross-sectional, sequential case series study of adult patients presenting to the Orthopedic Trauma Center between September 2009 and March 2010 with new limb fractures was performed. Hemoglobin A1c (HbA1c) and GA levels were measured in hyperglycemic patients with no prior diabetes mellitus. A receiver operating characteristic curve was plotted to examine the sensitivity, specificity, and positive and negative predictive values of GA in identifying occult diabetes in hospitalized patients with acute hyperglycemia. RESULTS: A total of 2,058 trauma patients were screened and 399 patients (19.4%) with no known diabetes mellitus were noted to be hyperglycemic. Of these 399 patients, 38.3% (n = 153) had ODM according to the HbA1c diagnosis cutoff point. GA level was strongly correlated with HbA1c using Pearson's correlation analysis (r = 0.887, p < 0.01). Using logistic regression analysis, GA (odds ratio [OR] = 1.60, p < 0.001) and fasting plasma glucose (OR = 1.974, p < 0.001) were identified as significant risk factors for the diagnosis of ODM. Receiver operating characteristic curve analysis showed that a GA value of 17.5% gave an optimal sensitivity of 73.20% and specificity of 99.12% for distinguishing ODM from stress-induced hyperglycemia. CONCLUSION: Almost 40% of nondiabetic orthopedic trauma patients presenting with hyperglycemia were found to have ODM. A GA value of 17.5%, the optimal cutoff point, could distinguish between ODM and stress-induced hyperglycemia in Chinese orthopedic trauma subjects. LEVEL OF EVIDENCE: II, diagnostic study. PMID- 22673269 TI - The effect of care bundle development on surgical site infection after hemiarthroplasty: an 8-year review. AB - BACKGROUND: Proximal femoral fracture is the most common reason for emergency orthopedic admission in the United Kingdom with an annual cost of L 1.7 billion to the National Health Service. Surgical site infection (SSI) after proximal femoral fracture increases patient morbidity and mortality. Methicillin-resistant Staphylococcus aureus (MRSA) poses a particular risk in this patient cohort as a large proportion of these patients are residents of long-term care facilities and are therefore transient or chronic carriers of MRSA. We recorded the effect of three stages of care bundle development on the infection and specifically the MRSA rate after hemiarthroplasty over an 8-year period. METHODS: Data were collated retrospectively from the surgical site infection surveillance service. These data were prospectively collected and independently collated. The data were analyzed using the chi(2) test and the normal test for differences between two proportions. RESULTS: Between October 2001 and June 2009, 1,830 hemiarthroplasties were performed. A statistically significant difference (p < 0.05) in SSI and MRSA rate was identified. The most effective care bundle included double skin preparation using alcoholic chlorhexidine, a single dose of intravenous co-amoxiclav (1.2 g) and gentamicin (240 mg) at induction, and implanted gentamicin-impregnated equine collagen at wound closure. CONCLUSIONS: Adoption of our care bundle approach led to a reduction in SSI rate after hemiarthroplasty. The care bundle we propose is tailored to reduce MRSA infection and minimize risks associated with antibiotic prophylaxis. It is a simple and cost-effective improvement in the clinical care of this vulnerable group. LEVEL OF EVIDENCE: IV, therapeutic study. PMID- 22673270 TI - Primary open reduction and internal fixation with headless compression screws in the treatment of Chinese patients with acute Lisfranc joint injuries. AB - BACKGROUND: Although primary open anatomic reduction and stable internal fixation has become a standard treatment principle of Lisfranc joint injuries, there are still some debates existed among surgeons as to the most appropriate treatment of this injury. The aim of this cohort study was to analyze the early (mean, 3.2 years) clinical and radiographic outcomes of one surgeon's experience associated with a standardized protocol of open reduction and internal fixation using headless compression screws (HCS) in a consecutive series of Chinese patients with Lisfranc joint injuries. METHODS: This study is to retrospectively evaluate the clinical and radiographic outcomes of a series of Chinese patients with Lisfranc joint injuries that underwent open reduction and internal fixation with HCS. RESULTS: There were 29 patients (30 feet) included in our study. The average score of American Orthopaedic Foot and Ankle Society Midfoot score and the Visual Analog Pain Scale were 80.6 and 2.4 points at the final follow-up point, respectively. Anatomic initial reduction was obtained in 26 patients (27 feet, 90%). At the last follow-up point, only one case had the loss of reduction. Posttraumatic osteoarthritis was observed in 10 patients (10 feet, 33%), and 2 of them (2 feet, 7%) were scheduled for arthrodesis because of persistent pain. CONCLUSION: Our results have shown that fixation of an unstable tarsometatarsal joint with AO 3.0 mm HCS can provide the firm stability, the precise reduction of the joint, and satisfactory short-term clinical and radiographic outcomes without any screw breakage, although posttraumatic osteoarthritis in the midfoot is still a significant challenge for orthopedic surgeons. PMID- 22673271 TI - Late reconstruction of posterior acetabular wall fractures using iliac crest. AB - BACKGROUND: Reconstructing late posterior acetabular wall fractures is challenging. This study evaluates the use of the iliac crest strut graft for posterior acetabular wall reconstruction. METHODS: From 1990 to 2004, seven patients (five males and two females) with traumatic posterior acetabular wall defects were reconstructed using autogenous iliac crest strut grafts. The mean age of the patients was 31 years. The mean time from injury to reconstruction was 6.4 months. The clinical (modified Merle d'Aubigne-Postel score) and radiologic evaluation (Matta score) were recorded at the final follow-up. RESULTS: The mean duration of follow-up was 76 months. On the basis of the modified Merle d'Aubigne Postel scoring system, the clinical outcomes at final follow-up were as follows: excellent for a pediatric patient; good for three adult patients without posttraumatic osteoarthritis of the hip at the time of reconstruction; and poor for three other adult patients with posttraumatic osteoarthritis of the hip at the time of reconstruction. Radiologic grading at the final follow-up was good in the pediatric patient; fair in three adult patients without posttraumatic osteoarthritis of the hip; and poor in three other patients with posttraumatic osteoarthritis of the hip. CONCLUSIONS: The reconstruction of the posterior acetabular wall defects using an iliac crest strut graft is a noteworthy technique for late posterior acetabular wall fracture. The technique may be an option for pediatric patients or adults without posttraumatic osteoarthritis of the hip at the time of reconstruction. However, it is not recommended for adult patients with posttraumatic osteoarthritis of the hip. In this case, total hip arthroplasty is a better choice. LEVEL OF EVIDENCE: IV, therapeutic study. PMID- 22673272 TI - Fixation of patella fractures with a minimally invasive tensioned wire method: compressive external fixation. AB - BACKGROUND: Current fixation methods of patella fractures are associated with hardware prominence, infection, and failure of fixation. These complications necessitate repeat surgical treatment, increase costs, and limit function. We investigated whether a novel device can effectively treat patella fractures with few complications. METHODS: A consecutive series of patients with displaced patella fractures with transverse and select other patterns were treated with the technique of compressive external fixation (CEF), a device based on an external tensioned wire construct. Patients were allowed unrestricted motion and weight bearing postoperatively. Patient outcomes were evaluated retrospectively. RESULTS: Eighty-four fractures (26 open) were treated with CEF with 23 performed percutaneously. All of the fractures attained union. The device was removed in the office at 6 weeks. Sixty-one patients regained excellent motion with a mean Insall knee score of 97 points, at an average follow-up of 4 years. Minor complications presented in 11% of patients but did not affect the overall outcome. Complications included minor wire irritation in 14 patients and one case of poor knee motion in a patient presenting with fibroankylosis of the joint. CONCLUSION: Treatment using the CEF technique is a safe and effective method of treatment of patella fractures with advantages over traditional forms of fixation particularly in cases with a poor soft tissue envelope, salvage situations, and in locations with limited resources. It allows for rapid recovery with minimal complications and no secondary surgery. Its use should be considered in the treatment of these injuries. LEVEL OF EVIDENCE: V, therapeutic study. PMID- 22673273 TI - Surgical management of posttraumatic elbow arthrofibrosis. AB - BACKGROUND: Functional loss of motion is a frequent complication after elbow trauma. The purpose of this study was to determine the effectiveness of open elbow release in restoring functional elbow motion. METHODS: A retrospective chart review of 177 adult patients who underwent open elbow release at our institution by the senior surgeon (D.P.H.) from 2003 to 2010 was performed. Seventy-seven of the elbow contracture releases were performed for posttraumatic elbow stiffness, with loss of flexion-extension. Burns and isolated proximal radioulnar exostosis resections were excluded. The mean age of patients was 45 years (range, 20-76 years), with 68 patients demonstrating radiographic evidence of heterotopic ossification (HO). The mean preoperative flexion-extension arc was 51 degrees. All patients were treated with the same surgical protocol, which included circumferential elbow capsulectomy, HO excision, hardware removal, and ulnar nerve neurolysis with submuscular anterior transposition. RESULTS: At a mean follow-up of 12 months (range, 3-56 months), the mean elbow flexion extension arc was 109 degrees representing a mean gain of 58 degrees. Sixty-nine percent (53 of 77 patients) achieved a minimum 100-degree functional elbow arc of motion. Six patients (8%) developed recurrent HO, with four undergoing secondary HO excision. One additional patient required manipulation under anesthesia in the early postoperative period. Complications included five infections, one postoperative fracture, one postoperative hematoma, and one radial head implant loosening. CONCLUSION: Open elbow contracture release and HO excision is an effective means of restoring functional elbow range of motion with a low complication rate. Furthermore, recurrent HO formation and elbow arthrofibrosis respond well to repeat surgical excision and contracture release. LEVEL OF EVIDENCE: IV, therapeutic study. PMID- 22673274 TI - Folded free vascularized fibular grafts for the treatment of subtrochanteric fractures complicated with segmental bone defects. AB - BACKGROUND: Subtrochanteric fractures of the femur complicated with segmental bone defects are uncommon injuries and challenging to manage. We evaluated the effect of reconstructing extensive bone defect in the subtrochanteric area (mean, 6.9 cm) with folded free vascularized fibular graft (FVFG). METHODS: Between 2001 and 2007, 14 cases of subtrochanteric fractures complicated with huge bone defects treated by folded FVFG transfer in our hospital were retrospectively reviewed. The defect was reconstructed by folded FVFG transfer and locking plate stabilization in 10 patients with no sign of infection at admission (group 1). In the other four patients presented with infections (group 2), the defect was reconstructed by folded FVFG transfer and external fixator fixation. The average follow-up period was 67.4 months. RESULTS: Bone union was achieved in all of the cases at an average of 5.4 months (range, 4-6 months). Primarily, bone union was achieved in all of the cases in group 1, but one stress fracture occurred in group 2. The full weight bearing time was 5.4 months (range, 5-6 months) in group 1 and 8.5 months (range, 8-9 months) in group 2. Seven patients in group 1 had the locking plate removed in an average of 27 months (range, 18-38 months). In group 2, the external fixator removal time was 13 months (range, 10-18 months). There was no varus deformity at the final follow-up in group 1. The neck-shaft angle measured during the postoperative period and at final follow-up was 129.6 degrees and 129.4 degrees, respectively. In group 2, the neck-shaft angle at the final follow-up was significantly less than the angle measured at the postoperative period (115.5 vs. 129.5 degree, p = 0.021). The range of motion of the hip and knee joint (extend and flex) was 100 degrees or more in all patients at the final follow-up. CONCLUSIONS: The results of this study showed that huge subtrochanteric bone defects reconstructed by folded FVFG and locking plate were highly successful in achieving bone union, reducing risks of postoperative stress fracture and preventing malunion. When huge bone defects in the subtrochanteric area complicated with acute or chronic infections, the technique of external fixator offers an alternative to reconstruct the stability of the proximal femur after folded FVFG. However, because of the inadequate stabilization, the risks of varus malunion and postoperative stress fracture could be increased after external fixator fixation. LEVEL OF EVIDENCE: V, therapeutic study. PMID- 22673275 TI - Nonagenarian hip fracture: treatment and complications. AB - BACKGROUND: Hip fracture is a common yet serious injury sustained by the elderly patient and represents one of the major healthcare challenges today. The aim of this study was to better define the unique characteristics of treating nonagenarian peritrochanteric hip fractures and their subsequent complications during hospital stay. METHODS: Seven hundred twenty-two patients underwent surgery for isolated fracture around the femoral neck. These patients were divided into one of three age groups: A, <50 years; B, 51-89 years; and C, >90 years. We performed a retrospective chart review to compare these groups in terms of patient characteristics, comorbidities, postoperative complications, fracture type, type of surgery performed, and mortality rate. RESULTS: There was no difference in time to surgery between groups. Comorbidities were similar in groups B and C but were higher than group A. Nonagenarians received a significantly greater percentage of hemiarthroplasties compared with those aged 51 years to 89 years. Cardiac complications were significantly higher in group C. In patients with sustained cardiac complications, the odds ratio for mortality was 15.88. CONCLUSIONS: Our results suggest that groups B and C were not significantly different pre- or intraoperatively. Nevertheless, there is an increase in cardiac complications and mortality in nonagenarians postoperatively. Nonagenarians should undergo similar treatment in the operating room compared with less elderly patients with the caveat that older patients, especially those with cardiac disease, may be more at risk for complication. The surgeon must evaluate the elderly patient with a hip fracture on a case-by-case basis, while ignoring chronological age. LEVEL OF EVIDENCE: III, prognostic study. PMID- 22673276 TI - Low-energy fracture of posterolateral tibial plateau: treatment by a posterolateral prone approach. AB - BACKGROUND: Most of the posterolateral tibial plateau fractures are caused by low energy injury. The posterior fracture fragment could not be exposed and reduced well through traditional approaches. The aim of this study was to review the results of surgical treatment of this kind of fracture using posterolateral approach with patient in prone position. METHODS: The low-energy posterolateral fracture is defined as the main part of articular depression or split fragment limited within the posterior half of the lateral column. Direct reduction and buttress plate fixation through the posterolateral prone approach was applied in all the patients. RESULTS: In our series, 15 of 132 (11.4%) patients with tibial plateau fractures were identified as low-energy posterolateral fractures. The clinical outcomes were available in 14 of the 15 patients through phone interviews and chart reviews. Mean follow-up was 35.1 months (range: 24-48 months). All the patients had anatomic or good reductions (<= 2 mm step/gap). Average range of motion was 0.7 degrees to 123.2 degrees (5-110 degrees to 0-140 degrees). The complications were limited to one superficial wound infection, two slight flexion contractures, and five implants removal. The average modified hospital for special surgery knee score was 93.4 (range: 86-100). CONCLUSIONS: The posterolateral prone approach provides excellent visualization, which can facilitate the reduction and posterior buttress plate fixation for low-energy posterolateral tibial plateau fractures and shows encouraging results. LEVEL OF EVIDENCE: V, therapeutic study. PMID- 22673277 TI - "Onion" flap: a novel technique for reconstruction of burn nail deformities. AB - BACKGROUND: Nail fold deformities from burn injury frequently result in eponychial retraction, proximal nail exposure, pain, and distal phalangeal function impairment. Secondary nail abnormalities including longitudinal ridges, surface cracks, and fragility are common sequelae to nail fold deformities. Surgical management of postburn nail fold deformity is challenging because of scar contractures involving the dorsum of digits and lack of surrounding healthy tissues that can be used as source of soft tissue for reconstruction. Previous reports have discussed several methods for reconstruction of these deformities. However, all of these methods are associated with significant donor site morbidities. METHODS: From August 2008 to January 2010, "onion" flap reconstruction was performed for postburn nail fold contractures and deformities on 32 fingers of eight patients (five men and three women; average age, 44.4 years; age range, 23-54 years). This novel technique was used to release scar contractures in the eponychial area and allow soft tissue restoration by redraping the eponychium in a single-step procedure. All 32 fingers received single-stage "onion" flap reconstruction for their nail fold deformities at least 6 months after the initial injury. RESULTS: The follow-up period, with an average of 7.8 months, revealed that all nails had good esthetic and functional results. All experienced amelioration of nail abnormalities. The "onion" advancement flap had effectively released the scar contracture around the nail fold and simultaneously restored the eponychial fold. CONCLUSIONS: The "onion" flap technique provides superior results compared with those from conventional techniques. We recommend it as the mainstay of treatment for reconstruction of the postburn eponychial deformities. LEVEL OF EVIDENCE: V, therapeutic study. PMID- 22673278 TI - Don't forget the posters! Quality and content variables associated with accepted abstracts at a national trauma meeting. AB - BACKGROUND: As a primary venue for presenting research results, abstracts selected for presentation at national meetings should be of the highest scientific merit and research quality. It is uncertain to what degree this is achieved as the methodological quality of abstracts submitted to national surgical meetings has not been previously described. The objective of this study was to evaluate abstracts presented at a leading trauma meeting for methodological quality. METHODS: All abstracts accepted for the 2009 American Association for the Surgery of Trauma meeting were reviewed and scored for methodological quality based on 10 criteria (scores, 0-10; 10 being the highest). Criteria were based on nationally published methodology guidelines. Two independent reviewers who were blinded to institution, region, and author reviewed each abstract. RESULTS: A total of 187 abstracts were accepted for presentation (67 oral and 120 posters). The most frequent clinical topics were shock/transfusion (23%), abdomen (12%), and nervous system (11%). Shock/transfusion abstracts were more common in the oral presentations (31% vs. 19%; p = 0.06). Abstracts from the northeast and south regions were the most common in both oral (26% and 29%) and posters (25% and 24%). Basic science accounted for 12% of accepted studies, while 51% were clinical and 28% were health services/outcomes. Only 8% of abstracts presented randomized data and only 11% reported null findings. Overall abstract scores ranged from 3 to 10 (median, 7; mean, 7.4). Abstracts selected for poster presentation had an overall higher score than those selected for oral presentation (7.4 +/- 1.7 vs. 6.8 +/- 1.7; p = 0.02). CONCLUSION: Although oral presentations traditionally receive the most attention and interest, the methodological quality of abstracts accepted for poster presentation equals (and sometimes exceeds) that of oral abstracts. Attendees of these national meetings should reconsider their time spent in viewing and visiting these poster sessions as with the oral presentations. In light of our findings, we highly encourage that all members and guests attend the American Association for the Surgery of Trauma Poster Rounds at each year's scientific assembly. PMID- 22673279 TI - A meta-analysis of percutaneous compression plate versus sliding hip screw for the management of intertrochanteric fractures of the hip. AB - BACKGROUND: Intertrochanteric hip fractures are associated with high morbidity and mortality rates. Percutaneous compression plating (PCCP) is a minimally invasive technique for fracture fixation that has been advocated to reduce blood loss, relieve pain, and lead to faster rehabilitation. The present systematic review and meta-analysis was performed to evaluate PCCP in patients with intertrochanteric hip fractures compared with patients with sliding hip screw (SHS). METHODS: A comprehensive review of related literature was conducted to identify all articles in PubMed, EMBASE, Springer, Ovid, China National Knowledge Infrastructure (CNKI), and the Cochrane Central Register of Controlled Trials published on or before July 26th, 2011. Only prospective or retrospective comparative studies reporting clinical and radiographic outcomes of PCCP for intertrochanteric hip fractures were included. The methodological qualities of the included studies were assessed using the Coleman methodology score, and the reported data of individual studies were extracted. Meta-analytic pooling of group outcomes across studies was performed for both the PCCP and SHS techniques. RESULTS: Fourteen studies met the inclusion criteria. Minimally invasive PCCP was associated with a decrease in surgical time, blood loss, transfusion rate, and systematic complications. No significant differences between PCCP and SHS were observed in other parameters, including hospital stay, mortality, reoperation, implant-related complications. CONCLUSIONS: Based on these finding, PCCP appeared similar to SHS in terms of mechanical stability in the clinical setting, but had obvious advantages in terms of blood loss, transfusion need, and systematic complications, which may be attributed to reduced soft tissue and bone damage. Although orthopedic surgeons are advised to consider PCCP fixation as an additional alternative treatment for intertrochanteric fractures, high-quality randomized trials are still needed to assess the benefits of this minimally invasive technique. LEVEL OF EVIDENCE: III, systematic review. PMID- 22673280 TI - Prolonged heparin-free extracorporeal membrane oxygenation in multiple injured acute respiratory distress syndrome patients with traumatic brain injury. AB - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) can be used as an "ultima ratio" strategy in multiple injured patients with severe thoracic trauma. However, systemic anticoagulation during ECMO is recommended and thus traumatic brain injury (TBI) and intracranial bleeding are well-accepted contraindications for ECMO therapy. METHODS: This report describes three cases of prolonged heparin free venovenous ECMO in multiple injured acute respiratory distress syndrome patients with severe TBI failing conventional mechanical ventilation. RESULTS: : Using this strategy, neither ECMO-associated bleeding nor clotting of the extracorporeal circuit occurred. All patients survived. CONCLUSIONS: Based on our experience, we recommend the use of heparin-free ECMO in multiple injured patients with pulmonary failure that is not successfully controlled by lung protective ventilation even if severe TBI is present. LEVEL OF EVIDENCE: IV, therapeutic study. PMID- 22673281 TI - A quick and easy closure technique for abdominal stab wound after diagnostic laparoscopy. PMID- 22673282 TI - Decompressive craniectomy versus craniotomy for head-injured patients with acute subdural hematoma. PMID- 22673283 TI - Bland-Altman plot agreement: It is time to stop the stab. PMID- 22673285 TI - Needle thoracostomy conclusions. PMID- 22673287 TI - Freeze drying (lyophilization) red blood cells. PMID- 22673292 TI - Smad7 inhibits differentiation and mineralization of mouse osteoblastic cells. AB - The transforming growth factor (TGF)-beta family members, bone morphogenetic protein (BMP)-2 and TGF-beta that signal via the receptor-regulated Smads (R Smads) induce bone formation in vivo. The inhibitory Smads (I-Smads), Smad6 and Smad7, negatively regulate TGF-beta family ligand signaling by competing with R Smads for binding to activated type I receptors, and preventing R-Smad activation, Hence, the I-Smads potentially act as suppressors of bone formation although their effects on phenotypic changes in mature osteoblasts are unclear. While Smad7 inhibits both BMP and TGF-beta signaling, Smad6 is less effective in inhibiting TGF-beta signaling. The present study was performed to examine the role of Smad7 on the phenotype of mouse osteoblastic MC3T3-E1 cells. We employed stable Smad7-transfected MC3T3-E1 cells to examine the role of Smad7 in osteoblast proliferation, differentiation and mineralization. Stable Smad7 overexpression significantly inhibited the absorbance in the MTT-dye assay and inhibited the levels of PCNA compared with those in empty vector-transfected cells. Smad7 overexpression suppressed the type 1 collagen mRNA and protein levels. Moreover, Smad7 inhibited ALP activity and mineralization of osteoblastic cells. The effects of stable overexpression of Smad6 were similar to those of Smad7 suggesting the changes mediated by either I-Smad occurred by inhibition of BMP rather than TGF-beta signaling. In addition, PTH-(1-34) elevated the levels of Smad7 in parental MC3T3-E1 cells. In conclusion, the present study demonstrated that Smad7, as well as Smad6, inhibits proliferation, differentiation and mineralization of mouse osteoblastic cells. Therefore, I Smads are important molecular targets for the negative control of bone formation. PMID- 22673293 TI - Low circulating adiponectin levels are associated with insulin resistance in non obese peritoneal dialysis patients. AB - In patients with end-stage renal disease (ESRD), circulating adipokine levels are increased due to decreased renal clearance, irrespective of obesity. However, whether adipokines play a role in the development of insulin resistance (IR) in non-obese ESRD patients is unknown. We conducted a cross-sectional study to identify factors associated with IR in 62 non-obese patients on peritoneal dialysis (PD). Non-obesity was defined as body mass index (BMI) <25 kg/m(2). IR was determined using homeostatic model assessment-IR (HOMA-IR). We also measured serum concentrations of adiponectin, leptin, resistin, high-sensitivity C reactive protein (hsCRP), and IL-6. The average BMI of the study patients was 21.6 kg/m(2). When patients were divided into two groups according to the median value of HOMA-IR, serum adiponectin levels were significantly lower in patients with HOMA-IR > 1.85 than in those with HOMA-IR <=1.85, whereas serum concentrations of leptin and resistin did not differ between the two groups. In addition, log-transformed HOMA-IR was negatively correlated with adiponectin (gamma = -0.464, P < 0.001) and log-transformed high-density lipoprotein cholesterol (gamma = -0.250, P = 0.050) and positively correlated with age (gamma = 0.334, P = 0.008) and triglyceride (gamma = 0.392, P = 0.002). However, resistin, log-transformed leptin and log-transformed hsCRP were not associated with HOMA-IR. In a multiple linear regression model, adiponectin was independently associated with HOMA-IR (beta = -0.023, P = 0.015). In conclusion, this study suggests that low circulating adiponectin levels might be involved in IR even in non-obese patients undergoing PD. PMID- 22673294 TI - Depression in patients with euthyroid chronic autoimmune thyroiditis. AB - Depression and chronic autoimmune thyroiditis are common diseases. The aim of this study was to determine whether the frequency of depression is elevated in patients with chronic autoimmune thyroiditis and normal thyroid function. A total of 201 subjects were included, of whom 107 and 94 participants were healthy or had euthyroid chronic autoimmune thyroiditis, respectively. Serum thyroid hormone levels and thyroid auto-antibodies were measured in all subjects. All participants were evaluated with Hamilton Depression Rating Scale (HDRS). HDRS scores of patients with euthyroid chronic autoimmune thyroiditis were higher than in healthy participants. This study suggests a possible association between depression and chronic autoimmune thyroiditis. The depression risk may be increased in patients with chronic autoimmune thyroiditis and normal thyroid function. PMID- 22673295 TI - Dysregulation of glucose metabolism even in Chinese PCOS women with normal glucose tolerance. AB - To clarify the necessity of improving glucose metabolism in polycystic ovary syndrome (PCOS) women as early as possible, 111 PCOS women with normal glucose tolerance and 92 healthy age-matched controls were recruited to investigate glucose levels distribution, insulin sensitivity and beta cell function. 91 PCOS women and 33 controls underwent hyperinsulinemic-euglycemic clamp to assess their insulin sensitivity, which was expressed as M value. beta cell function was estimated by homeostatic model assessment (HOMA)-beta index after adjusting insulin sensitivity (HOMA-betaad index). Compared with lean controls, lean PCOS women had similar fasting plasma glucose (FPG), higher postprandial plasma glucose (PPG) (6.03+/-1.05 vs. 5.44+/-0.97 mmol/L, P<0.05), lower M value but similar HOMA-betaad index, while overweight/obese PCOS women had higher levels of both FPG (5.24+/-0.58 vs. 4.90+/-0.39, P<0.05) and PPG (6.15+/-0.84 vs. 5.44+/ 0.97 mmol/L, P<0.05), and lower levels of both M value and HOMA-betaad index. Linear regression and ROC analysis found BMI was independently associated with M value and HOMA-betaad index in PCOS women separately, and the cutoff of BMI indicating impaired beta cell function of PCOS women was 25.545kg/m2. In conclusion, insulin resistance and dysregulation of glucose metabolism were common in Chinese PCOS women with normal glucose tolerance. BMI >= 25.545kg/m2 indicated impaired beta cell function in PCOS women with normal glucose tolerance. PMID- 22673296 TI - A case of glycogenic hepatopathy developed in a patient with new-onset fulminant type 1 diabetes: the role of image modalities in diagnosing hepatic glycogen deposition including gradient-dual-echo MRI. AB - Glycogenic hepatopathy (GH) has been reported as a very rare and under recognized complication in long-standing poorly controlled type 1 diabetes (T1D) patients. GH is characterized by transient elevation of liver transaminase and hepatomegaly caused by reversible and excessive glycogen accumulation in hepatocytes. It has been reported that GH is indistinguishable from non-alcoholic fatty liver disease, which is more commonly seen in diabetic patients, even after a history is taken and a physical examination or imaging studies have been performed. GH can only be diagnosed by liver biopsy. We here demonstrate a 21-year-old male patient with new-onset fulminant T1D complicated with diabetic ketoacidosis who subsequently developed GH just after the initiation of insulin treatment. The marked liver dysfunction (serum levels of aspartate aminotransferase 769 IU/L and alanine aminotransferase 1348 IU/L) and hepatomegaly improved spontaneously via glycemic control without any specific treatments thereafter. Moreover, the insulin requirement dramatically decreased from 168 to 80 units per day as GH improved, suggesting a potential role of GH in insulin resistance. GH was diagnosed based on the histological findings of the liver in our case, but we were able to predict GH before the biopsy based on the findings in the gradient dual-echo magnetic resonance imaging sequence combined with ultrasound and/or computed tomography examinations of the liver. PMID- 22673297 TI - [Relatedness of occupational exposure to whole-body vibration and health, principally back symptoms]. AB - OBJECTIVES: DISCUSSION is continuing about whether or not to update the Occupational Exposure Limit for Whole Body Vibration exposure (OELWBV) which was established in 1975 as a part of the Recommendation of Occupational Exposure Limits (OEL), issued by the Japan Society for Occupational Health. The objectives of this study were to clarify the necessity of the update and the adverse health effects of whole-body vibration by reviewing the literature and to help to compile a for detailed revisions. SUBJECTS AND METHODS: Mainly referring to our preceding review, the current OELWBV exposure was examined. The relatedness of adverse health effects, principally back symptoms and occupational exposure to whole-body vibration (WBV) was examined by reviewing review papers, the original English papers referred to in those papers, and original English and Japanese references from 2002 to 2010 retrieved through a MEDLINE search. RESULTS: The results show the necessity of updating the present OELWBV as soon as possible. The overwhelming majority of the literature consists of epidemiological studies showing the relatedness of WBV to back symptoms. Thirty epidemiological studies out of 28 literatures clearly show the presence of a relationship between WBV and back symptoms. Various indices of exposure to WBV and back symptoms show the dose response relationships. Among these, a few studies used A(sum)(8) (equivalent 8 hour r.m.s. acceleration value for the combined frequency-weighted vibration of three diagonal, that is x, y and z, axes) as the exposure index. All of these studies reported some dose-response relationship between WBV exposure and back symptoms. DISCUSSION: Despite the clear presence or absence of a relationship between WBV and back symptoms, 0.5 m/s(2) seems to be the unconfirmed threshold of risk. Focusing on data of A(sum)(8), we suggest that the risk increases over the magnitude of 0.30 m/s(2). To clarify this, further epidemiological studies and others should focus on A(sum)(8) around 0.30 m/s(2). CONCLUSIONS: The present OEL of WBV should be examined from the viewpoint of the risks of back symptoms referring to the epidemiological studies that show the larger risks of back symptoms in comparison with unexposed referent workers. We conclud that when updating the present OELWBV, A(sum)(8) should be taken into account for back symptoms, referring to the findings of epidemiological studies. PMID- 22673298 TI - Standing wave brass-PZT square tubular ultrasonic motor. AB - This paper reports a standing wave brass-PZT tubular ultrasonic motor. The motor is composed of a brass square tube with two teeth on each tube end. Four PZT plates are attached to the outside walls of the brass tube. The motor requires only one driving signal to excite vibration in a single bending mode to generate reciprocating diagonal trajectories of teeth on the brass tube ends, which drive the motor to rotate. Bi-directional rotation is achieved by exciting different pairs of PZT plates to switch the bending vibration direction. Through using the brass-PZT tube structure, the motor can take high magnitude vibration to achieve a high output power in comparison to PZT tube based ultrasonic motors. Prototypes are fabricated and tested. The dimension of the brass-PZT tube is 3.975mm*3.975mm*16mm. Measured performance is a no-load speed of >1000RPM, a stall torque of 370MUNm and a maximum output power of 16 mW when a sinusoidal driving voltage of 50V is applied. The working frequencies of the motor are 46,050Hz (clockwise) and 46,200Hz (counter-clockwise). PMID- 22673299 TI - Immunomodulatory synergy by combining atorvastatin and rapamycin in the treatment of experimental autoimmune encephalomyelitis (EAE). AB - Combination therapies are gaining momentum over monotherapies in the treatment of multiple sclerosis (MS). Suboptimal doses of atorvastatin and rapamycin prevented or reversed clinical and histologic experimental autoimmune encephalomyelitis (EAE). Secretion of proinflammatory Th1 and Th17 cytokines was reduced and Th2 and Treg cytokine secretion was increased in mice. Combination therapy promoted induction of Treg cells and attenuated the infiltration of inflammatory IL-17 cells in EAE. It appeared that rapamycin-reactivated ERK was blunted by addition of atorvastatin. Our results demonstrate that agents with different mechanisms of immune modulation can combine synergistically in treating CNS autoimmunity. PMID- 22673300 TI - Pulmonary ventilation should be matched with pulmonary perfusion during cardiopulmonary bypass. PMID- 22673301 TI - Interpretation of elevated transvalvular pressure gradients across a tilting-disc mitral valve in the setting of severe aortic insufficiency. PMID- 22673302 TI - High transvalvular gradients across a prosthetic valve in the mitral position: not ignoring the bigger picture. PMID- 22673303 TI - Suspended hybrid films assembled from thiol-capped gold nanoparticles. AB - In this work, we explored the formation processes of suspended hybrid thin films of thiol-capped Au nanoparticles (AuNPs) inside metal oxide tubular structures. We found that a balance between in-film interactions of the AuNPs and boundary interactions with metal oxides is a key in making these special organic-inorganic thin films. The hybrid films process many processing advantages and flexibilities, such as controllable film thickness, interfacial shape and inter AuNPs distance, tuning of particle sizes, thiol population, chain lengths, and other new properties by introducing functional groups to thiol chains. Among their many unique features, the assembly-disassembly property may be useful for future on-off or store-release applications. PMID- 22673304 TI - In silico analyses of primers used to detect the pathogenicity genes of Vibrio cholerae. AB - In Vibrio cholerae, the etiological agent of cholera, most of the virulence genes are located in two pathogenicity islands, named TCP (Toxin-Co-regulated Pilus) and CTX (Cholera ToXins). For each V. cholerae pathogenicity gene, we retrieved every primer published since 1990 and every known allele in order to perform a complete in silico survey and assess the quality of the PCR primers used for amplification of these genes. Primers with a melting temperature in the range 55 60 degrees C against any target sequence were considered valid. Our survey clearly revealed that two thirds of the published primers are not able to properly detect every genetic variant of the target genes. Moreover, the quality of primers did not improve with time. Their lifetime, i.e. the number of times they were cited in the literature, is also not a factor allowing the selection of valid primers. We were able to improve some primers or design new primers for the few cases where no valid primer was found. In conclusion, many published primers should be avoided or improved for use in molecular detection tests, in order to improve and perfect specificity and coverage. This study suggests that bioinformatic analyses are important to validate the choice of primers. PMID- 22673305 TI - Analysis of the ion adsorption-desorption characteristics of biofilm matrices. AB - The characteristics of biofilm polymers formed on stone surfaces in Lake Biwa and ion adsorption and desorption to and from these biofilms were investigated. The results indicated that both positively and negatively charged sites exist in the biofilm polymer. A physicochemical interaction between these sites and ions in the surrounding water seems to promote the adsorption of ions to the biofilm through an attractive electrostatic interaction and an ion-exchange mechanism. The results also indicated that, in comparison with ion-exchange resins, ions were more loosely bound to and desorbed more easily from the biofilm polymer. This suggests that microbes in the biofilm can readily use these ions as nutrient ions. Our present findings indicate that the biofilm may play an important role in supplying nutrient ions to microbes in the biofilm and in the development of a nutrient-rich environment within the biofilm through both ion adsorption and desorption. This study shows for the first time that the inside of a biofilm can be a sustainable environment for microbes. PMID- 22673306 TI - Diversification of bacterial community composition along a temperature gradient at a thermal spring. AB - To better understand the biogeography and relationship between temperature and community structure within microbial mats, the bacterial diversity of mats at a slightly alkaline, sulfide-containing hot spring was explored. Microbial mats that developed at temperatures between 75-52 degrees C were collected from an area of approximately 1 m(2) in Nakabusa, Nagano, Japan. Bacterial 16S rRNA genes from these samples were examined by terminal restriction fragment length polymorphism (T-RFLP) and clone library analysis. T-RFLP profiles revealed 66 unique fragments (T-RFs). Based on total T-RFs observed in environmental profiles and clone libraries, a temperature effect on diversity was determined, with complexity in the community increasing as temperature decreased. The T-RF pattern indicated four distinct community assemblages related to temperature. Members of the Aquificales and particularly the sulfur-oxidizing bacterium Sulfurihydrogenibium were present at all temperatures and were the dominant component of mats taken at 75-67 degrees C. Sulfide oxidation, which persisted throughout the temperature gradient, was the presumed dominant pathway of primary production above 67 degrees C. As temperature decreased, successive additions of anoxygenic and oxygenic phototrophs increased primary productivity, allowing for diversification of the community. PMID- 22673307 TI - Tetracycline resistance and presence of tetracycline resistance determinants tet(V) and tap in rapidly growing mycobacteria from agricultural soils and clinical isolates. AB - Rapidly growing mycobacteria (RGM) inhabit soil and water but certain strains represent a health risk for human and animals. Both clinical and soil RGM may be under selection pressure for resistance to tetracycline (TET) antibiotics, since tetracyclines are administrated to humans and farm animals, and TET residues enter soil through manuring; however, resistance to TET and the presence of TET resistance genes have been assessed only in clinical isolates. We were therefore interested in comparing soil and clinical RGM in terms of TET resistance and the presence of TET-resistance genes. We used 44 RGM from grasslands with different exposure to animal manure, and 38 clinical RGM from Czech hospitals. There was no difference between the clinical and soil isolates in TET resistance, with >50% resistant isolates in both groups. otr(A), otr(B), tet(K), tet(L) or tet(M) were not detected in any soil or clinical isolate. In contrast, most isolates harbored tet(V) and tap, both encoding mycobacterial efflux pumps, including species where these genes have never been evidenced before. The phylogeny of tet(V) correlated with isolates' BOX-PCR profiles, suggesting that this gene evolved along with mycobacterial genomes as a part of the intrinsic resistome. In certain cases, tet(V) and/or tap were found in TET-sensitive isolates, or inversely, were not found in resistant strains. Concluding, intrinsic efflux pumps may be more important for TET resistance than horizontally transferred genes in both soil and clinical RGM. Their simple presence, however, does not attest to resistance, and therefore their diversity, function and expression merit further research. PMID- 22673310 TI - Genome-wide association study identifies common variants at TNFRSF13B associated with IgG level in a healthy Chinese male population. AB - IgG has a crucial role in humoral immune response. Serum IgG level is mainly determined under genetic control. To explore the genetic influence on serum IgG levels, a two-stage genome-wide association study (GWAS) was performed in a healthy Chinese population of 3495 men, including 1999 unrelated subjects in the first stage and 1496 independent individuals in the second stage. Three single nucleotide polymorphisms (SNPs) located in TNFRSF13B on 17p11.2 or nearby were significantly associated with IgG level: rs4792800 in the intron (combined P value=1.45 * 10(-12)), rs12603708 in the intron (combined P-value=1.82 * 10(-8)) and rs3751987 at ~65 kb downstream of the 5'-UTR region of TNFRSF13B (combined P value=3.67 * 10(-9)). Additionally, smoking was identified to be associated with IgG level in both stages (P<0.001), but there was no significant interaction between smoking and the identified SNPs (P>0.05). The strong association between variants at TNFRSF13B and IgG level may be helpful to further explore the biological mechanism by which the serum IgG is affected by transmembrane activator, calcium modulator and cyclophilin ligand interactor encoded by TNFRSF13B. PMID- 22673309 TI - Variation in human genes encoding adhesion and proinflammatory molecules are associated with severe malaria in the Vietnamese. AB - The genetic basis for susceptibility to malaria has been studied widely in African populations but less is known of the contribution of specific genetic variants in Asian populations. We genotyped 67 single-nucleotide polymorphisms (SNPs) in 1030 severe malaria cases and 2840 controls from Vietnam. After data quality control, genotyping data of 956 cases and 2350 controls were analysed for 65 SNPs (3 gender confirmation, 62 positioned in/near 42 malarial candidate genes). A total of 14 SNPs were monomorphic and 2 (rs8078340 and rs33950507) were not in Hardy-Weinberg equilibrium in controls (P<0.01). In all, 7/46 SNPs in 6 genes (ICAM1, IL1A, IL17RC, IL13, LTA and TNF) were associated with severe malaria, with 3/7 SNPs in the TNF/LTA region. Genotype-phenotype correlations between SNPs and clinical parameters revealed that genotypes of rs708567 (IL17RC) correlate with parasitemia (P=0.028, r(2)=0.0086), with GG homozygotes having the lowest parasite burden. Additionally, rs708567 GG homozygotes had a decreased risk of severe malaria (P=0.007, OR=0.78 (95% CI; 0.65-0.93)) and death (P=0.028, OR=0.58 (95% CI; 0.37-0.93)) than those with AA and AG genotypes. In summary, variants in six genes encoding adhesion and proinflammatory molecules are associated with severe malaria in the Vietnamese. Further replicative studies in independent populations will be necessary to confirm these findings. PMID- 22673311 TI - Variation in FCN1 affects biosynthesis of ficolin-1 and is associated with outcome of systemic inflammation. AB - Ficolin-1 is a recognition molecule of the lectin complement pathway. The ficolin 1 gene FCN1 is polymorphic, but the functional and clinical consequences are unknown.The concentration of ficolin-1 in plasma and FCN1 polymorphisms in positions -1981 (rs2989727), -791 (rs28909068), -542 (rs10120023), -271 (rs28909976), -144 (rs10117466) and +7918 (rs1071583) were determined in 100 healthy individuals. FCN1 expression by isolated monocytes and granulocytes and ficolin-1 levels in monocyte culture supernatants were assessed in 21 FCN1 genotyped individuals. FCN1 polymorphisms were determined in a cohort of 251 patients with systemic inflammation. High ficolin-1 plasma levels were significantly associated with the minor alleles in position -542 and -144. These alleles were also significantly associated with high FCN1 mRNA expression. The level of ficolin-1 in culture supernatants was significantly higher in individuals homozygous for the minor alleles at positions -542 and -144. Homozygosity for these alleles was significantly associated with fatal outcome in patients with systemic inflammation. None of the other investigated polymorphisms were associated with FCN1 and ficolin-1 expression, concentration or disease outcome. Functional polymorphic sites in the promoter region of FCN1 regulate both the expression and synthesis of ficolin-1 and are associated with outcome in severe inflammation. PMID- 22673312 TI - Gastrointestinal symptoms and quality of life in screen-detected celiac disease. AB - BACKGROUND: Active serological screening has proved an effective means of increasing the diagnostic rate in celiac disease. The effects of a long-term gluten-free diet on possible gastrointestinal symptoms and psychological well being in screen-detected patients have nevertheless remained obscure. METHODS: Abdominal symptoms and quality of life were measured in a large cohort of treated screen-detected celiac adults. Comparisons were made with corresponding symptom detected patients and with non-celiac controls. Dietary adherence was assessed both by structured interview and by serological testing. RESULTS: In both screen- and symptom-detected celiac groups, 88% of the patients were adherent. On a diet, both screen- and symptom-detected patients reported significantly more gastrointestinal symptoms than non-celiac controls. Those screen-detected patients who reported having no symptoms at the time of diagnosis, also remained asymptomatic during the diet. Despite persistent symptoms, psychological well being in screen-detected patients was comparable with that in non-celiac controls, whereas the symptom-detected patients showed lower quality of life. CONCLUSION: Long-term treated screen-detected celiac patients, especially women, suffer from gastrointestinal symptoms on a gluten free diet similarly to symptom detected patients. However, despite a similar frequency of persistent symptoms, the quality of life was unimpaired in the screen found, but remained low in the symptom-detected group. PMID- 22673313 TI - Bone marrow aspirate collection and preparation--a comparison of three methods. AB - PURPOSE: Preparing bone marrow smears using non-anticoagulated bone marrow aspirate is a traditional practice but many laboratories now use anticoagulated aspirate samples in K-EDTA. There are no published studies comparing the effectiveness of these two methods. This report compares the readability of slides, prepared using non-anticoagulated and anticoagulated methods, from three laboratories in Hamilton Ontario. METHODS: A blinded set of 129 aspirate slides prepared using anticoagulated and non-anticoagulated methodologies (using K-EDTA) was reviewed by three reviewers. Slides were classified as unreadable if two of the three observers rejected them based on a standardized survey. RESULTS: The proportion of slides classed as unreadable varied widely (5.0% to 46.9%) depending on collection and slide preparation methods. Degree of coagulation did not affect readability. CONCLUSION: A measurable advantage to using non anticoagulated bone marrow was not demonstrated. Immediate anticoagulation of bone marrow samples, with laboratory personnel at the bedside to assess sample quality, followed by slide preparation in the laboratory provided the best results. PMID- 22673314 TI - PEG10 promotes the migration of human Burkitt's lymphoma cells by up-regulating the expression of matrix metalloproteinase-2 and -9. AB - PURPOSE: Paternally expressed gene 10 (PEG10) is important for apoptosis resistance in cancer cells; however, the effect of PEG10 on tumor cell migration remains poorly understood. In this study, we investigated the effects of PEG10 on proliferation, apoptosis, adhesion and migration in the Burkitt's lymphoma cell line, Raji. METHODS: Apoptosis was induced by 5-fluorouracil (5-FU) in pcDNA3.0/PEG10 transiently transfected HEK293T cells and PEG10-suppressed Raji cells. siRNAPEG10 was used to inhibit PEG10 expression. Fluorescence-activated cell sorting (FACS) were performed to analyze the effect of PEG10 on apoptosis. CCK-8 were performed to detect cell proliferation and adhesion. Matrigel invasion were performed using PEG10-suppressed Raji cells to investigate cell migration. The expression levels of matrix metalloproteinases -2and -9 (MMP-2 and MMP-9) were analyzed in PEG10-suppressed Raji cells using both real-time RT-PCR and Western blot analysis. RESULTS: HEK293T cells that overexpressed PEG10 exhibited greater viability 48 h following treatment with 5-FU, relative to control cells. Specific inhibition of PEG10 expression by siRNA resulted in inhibition of growth and apoptosis in Raji cells. Adherence and invasion capabilities were downregulated and expression levels of MMP-2 and MMP-9 were reduced in PEG10 suppressed Raji cells. CONCLUSIONS: Our findings demonstrated that PEG10 enhances the apoptotic resistance and viability of Raji cells. The migration and adherence invasion capacity of Raji cells could potentially be affected by regulation of the expression of MMP-2 and MMP-9. Our research provides a promising strategy for cancer immunotherapy of lymphoma. PMID- 22673315 TI - Evaluation of sleeping energy expenditure using the SenseWear Armband in patients with overt and subclinical hypothyroidism. AB - PURPOSE: The aim of the present study was to evaluate the average sleeping energy expenditure (EE) levels using the SenseWear Armband (SWA) in patients with overt and subclinical hypothyroidism. METHODS: Sixty patients with hypothyroidism and 30 healthy individuals were recruited for the study. Hypothyroid patients were divided into two groups: group 1 (n = 30) consisted of patients with overt hypothyroidism and group 2 (n = 30) consisted of patients with subclinical hypothyroidism. Lastly, group 3 (n = 30) consisted of healthy subjects. The average EE and metabolic equivalent of task (MET) values during sleep of all the hypothyroid participants were analyzed at baseline and at the end of the study. Data were also obtained from the healthy subjects at baseline. RESULTS: The average sleeping EE and METs values were not significantly different at baseline. Similarly, these values did not change significantly after achieving a euthyroid state via thyroid hormone replacement (both p > 0.05). CONCLUSIONS: Contrary to what has been previously reported , the average sleeping EE and METs values in all hypothyroid patients and healthy individuals were similar at baseline and did not change in the patients with overt and subclinical hypothyroidism after achievement of a euthyroid state. PMID- 22673316 TI - Subcutaneous versus intraperitoneal insulin for patients with diabetes mellitus on continuous ambulatory peritoneal dialysis: meta-analysis of non-randomized clinical trials. AB - BACKGROUND: Diabetes mellitus is one of the leading causes of end stage renal disease. Use of intraperitoneal (IP) nsulin in diabetic patients on peritoneal dialysis (PD) can restore glucose control to near normal values. The safety and efficacy of this method is unclear. METHODS: We performed a meta-analysis to study the safety and efficacy of IP insulin administration in diabetic patients on PD. The primary outcome measures is glycemic control: secondary outcome measures were plasma lipids, insulin dose requirement/day and the risk of peritonitis and hepatic subcapsular steatosis. Medline, EMBASE, Cochrane Central Register of Controlled Trials, and reference lists of eligible studies were searched. Eligible studies included randomized and non-randomized controlled trials that allocated adult PD diabetic patients to IP insulin and subcutaneous (SC) insulin. RESULTS: Twenty one citations were identified and three met the eligibility criteria. Glycemic control with IP insulin, as assessed with HbA1C, was equal to or better than that obtained with SC insulin: weighted mean difference was -1.49 % (95% CI: -2.17 to - 0.27, p=0.0001). The insulin dose required was more than two-fold higher in the IP treatment. Serum HDL-cholesterol decreased during IP insulin therapy while serum triglyceride (TG) concentration tended to increase, in comparison with levels seen in patients treated with SC insulin. CONCLUSIONS: Use of IP insulin provides adequate glycemic control, which appears superior to that seen following treatment with conventional SC insulin. The plasma lipids are adversely affected by IP insulin, possibly contributing to increased cardiovascular risk. Data are limited and further studies are needed to assess for the long-term safety of this approach. PMID- 22673317 TI - Increased oxidized-LDL levels and arylesterase activity/HDL ratio in ESRD patients treated with hemodialysis. AB - PURPOSE: Investigations, in which oxidized-low density lipoprotein (ox-LDL), serum paraoxonase (PON1) and homocysteine (Hcy) are considered together as important agents involved in the development of oxidative and atherogenic events in non-diabetic hemodialysis (HD) population, are limited. This case-control study was designed to evaluate these parameters in the patients and control subjects and to determine the correlations among the factors. METHODS: Forty-nine age- and sex- matched subjects, including 28 non-diabetic HD patients (paired pre and post-dialysis samples) and 21 control subjects, were enrolled. Ox-LDL and Hcy levels were measured with ELISA and EIA methods, respectively. Arylesterase activity of PON1 was measured by spectrophotometric assay. RESULTS: Compared with the control group, ox-LDL levels were significantly increased both before (p=0.001) and after HD (p=0.036). Arylesterase activity-to-HDL ratio in HD patients was significantly higher than control subjects (p=0.003). Homocysteine levels in the ESRD patients were higher than control subjects both in pre dialysis and post-dialysis. There was a significant positive correlation (r= 0.25, p= 0.026) between ox-LDL and homocysteine in samples obtained before HD. Logistic regression analysis revealed ox-LDL levels (OR=3.02, p < 0.001) and arylesterase activity/HDL ratio (OR=2.43, p=0.01) to be associated with the increased risk of ESRD. CONCLUSIONS: Ox-LDL levels and arylesterase activity/HDL ratio indicated the strongest association with ESRD risk. These factors, especially ox-LDL as an indicator of oxidative stress, may be biomarkers in evaluating the status of non-diabetic ESRD patients. Because of the pathogenic relationship between ox-LDL and homocysteine as nontraditional risk factors of atherosclerosis, therapeutic strategies adopted to reduce them may be useful in decrease of high prevalence of cardiovascular mortality in dialysis patients. In addition, measurement of PON1 activity to HDL ratio is possibly a more valuable biomarker than arylesterase activity alone in non-diabetic ESRD. PMID- 22673318 TI - Prevalence of atrial fibrillation in patients taking TSH suppression therapy for management of thyroid cancer. AB - BACKGROUND: Suppression of thyroid stimulating hormone (TSH) below the normal range with administration of L-thyroxine has been shown to improve survival in patients treated for thyroid cancer (TC). Although most TC patients require long term TSH suppression therapy, the effect of this treatment on cardiac rhythm remains unknown. A cross-sectional study was conducted to determine the prevalence of atrial fibrillation (AF) in TC patients on TSH suppressive therapy. METHODS: All TC patients seen between June 2009 and March 2010 through a multidisciplinary thyroid oncology clinic, Halifax, Nova Scotia, Canada, for whom TSH suppressive therapy had previously been recommended, were recruited into the study. Each patient underwent an electrocardiogram and filled out a questionnaire relevant to causes, signs/symptoms of AF and/or its complications. The prevalence of AF in this population then was compared against the published prevalence of AF in general populations. RESULTS: A total of 351 patients were seen in the thyroid clinic of which 136 patients met the inclusion criteria for the study. The mean age was 52 years, 85% were female, and mean follow-up duration prior to recruitment was 11 years. The mean TSH was 0.17 mIU/L (Normal: 0.35 - 5.5 mIU/L). There were 14 patients found to have AF (two patients had long-standing persistent AF and 12 patients had paroxysmal AF). The mean ages of patients with and without AF were 61.6 years and 51.4 years, respectively (P = 0.01). Prevalence of AF in the study group was 10.3%; the rate of AF in the TC patients aged 60 years and over (17.5%) was higher than the rate of AF in published data in people 60 years and over (P < 0.001). AF was diagnosed after the initiation of the TSH suppression therapy in all except one patient. CONCLUSION: TSH suppression in thyroid cancer is associated with a high prevalence of AF, particularly in older individuals. PMID- 22673319 TI - In vitro antibacterial activity of zinc oxide on a broad range of reference strains of intestinal origin. AB - Minimal inhibitory concentrations (MIC) and growth behaviour in ZnO supplemented media were determined by the broth micro dilution method against 75 reference strains. No clear clustering according to bacterial group was observed, but 10 of 11 Lactobacillaceae strains showed high zinc resistance (>=520 MUg mL(-1)). Enterobacterial strains showed high (6/11) to medium resistance (5/11). The Clostridia and Bacteroidaceae strains exhibited a diverse range of MIC. The results of this study show that zinc resistance of commensal intestinal bacteria cannot be grouped according to their taxonomic origin and therefore, the antibacterial activity of ZnO in the intestine of farm animals cannot be generalized. PMID- 22673320 TI - Genomic analysis of bovine herpesvirus type 4 (BoHV-4) from Argentina: high genetic variability and novel phylogenetic groups. AB - Bovine herpesvirus 4 (BoHV-4) is a gamma-herpesvirus that has been isolated both from apparently healthy animals and from cattle with a variety of clinical signs, including post-partum endometritis and abortion. BoHV-4 causes either a persistent or a latent infection in cells of the monocyte/macrophage lineage. Two groups of BoVH-4 strains have been defined based on their restriction patterns: the Movar-like strains (European prototype) and the DN 599-like strains (American prototype). The purpose of the present study was to genetically characterize wild type BoHV-4 strains isolated from vaginal discharges of aborted cows in Argentina. The virus was identified by isolation and nested PCR in all vaginal discharge samples from aborted cows, either as a sole agent or in association with other pathogens. Restriction enzyme profiling and phylogenetic analysis demonstrated that there is a high genetic variability among the studied field isolates. The existence of three groups of strains, which were designated as genotypes 1, 2 and 3, is described. Genotypes 1 and 2 possibly correspond to the Movar-like and DN 599-like groups, respectively, whereas Genotype 3 corresponds to a novel group. Two viral strains did not cluster into any of these three groups, indicating that other genotypes could be circulating in Argentina. These results suggest a complex epidemiological background for the Argentinean BoHV-4 strains, probably influenced by independent events of genetic drift. This hypothesis cannot be rejected based on the available data. However, there is no direct evidence supporting this possibility. Thus, it seems speculative to suggest that interspecific jumps are responsible for the observed phylogenetic grouping. On the other hand, our analyses suggest a geographical structure for the observed viral genotypes, since genotypes 1 and 2 included the European (Movar-like) and American (DN599-like) reference strains, respectively. Geographic dispersion is known to be a driver of herpes viruses diversification, and independent evolution in geographical isolated places ensures the emergence of particular mutations in each location due to genetic drift (Compans, 2007; Zong et al., 1999). Therefore, at this point, the genetic drift hypothesis is the one that requires less ad-hoc considerations and thus, to our understanding, is the one that fits to the findings from this study. The involvement of this genetic variability in the detection and pathogenesis of BoHV-4 remains to be investigated. PMID- 22673322 TI - Neural basis of improved ITD sensitivity with jitter. PMID- 22673321 TI - Spatial and temporal properties of eye movements produced by electrical stimulation of semicircular canal afferents. AB - To investigate the characteristics of eye movements produced by electrical stimulation of semicircular canal afferents, we studied the spatial and temporal features of eye movements elicited by short-term lateral canal stimulation in two squirrel monkeys with plugged lateral canals, with the head upright or statically tilted in the roll plane. The electrically induced vestibuloocular reflex (eVOR) evoked with the head upright decayed more quickly than the stimulation signal provided by the electrode, demonstrating an absence of the classic velocity storage effect that improves the dynamics of the low-frequency VOR. When stimulation was provided with the head tilted in roll, however, the eVOR decayed more rapidly than when the head was upright, and a cross-coupled vertical response developed that shifted the eye's rotational axis toward alignment with gravity. These results demonstrate that rotational information provided by electrical stimulation of canal afferents interacts with otolith inputs (or other graviceptive cues) in a qualitatively normal manner, a process that is thought to be mediated by the velocity storage network. The observed interaction between the eVOR and graviceptive cues is of critical importance for the development of a functionally useful vestibular prosthesis. Furthermore, the presence of gravity dependent effects (dumping, spatial orientation) despite an absence of low frequency augmentation of the eVOR has not been previously described in any experimental preparation. PMID- 22673323 TI - Skin incision-induced receptive field responses of mechanosensitive peripheral neurons are developmentally regulated in the rat. AB - Maturation of the nervous system results in changes in both central and peripheral processing. To better understand responses to injury in the young, developmental differences in the acute response to incision were investigated in both tactile and nociceptive myelinated peripheral mechanosensitive afferent neurons in vivo. Neuronal intrasomal recordings were performed in juvenile and infant rats in 34 L5 dorsal root ganglia, and each neuron was phenotypically defined. Neurons had a mechanosensitive receptive field in the glabrous skin on the plantar surface of the hind paw, which was characterized at baseline and for up to 45 min after incision. Fundamental maturational differences in the effect of incision were clear: in high-threshold nociceptive mechanoreceptors, the mechanical threshold decreased immediately and the receptive field size increased rapidly in juvenile rats but not in infant rats. Additionally, a divergence in changes in the instantaneous response frequency of tactile afferents occurred between the two ages. These differences may help explain maturational differences in responses to peripheral injury and suggest that differences in central nervous system responses may be partially mitigated by spatially confined and frequency dependent differences resulting from tactile and nociceptive mechanosensitive input. PMID- 22673324 TI - Shape encoding consistency across colors in primate V4. AB - Neurons in primate cortical area V4 are sensitive to the form and color of visual stimuli. To determine whether form selectivity remains consistent across colors, we studied the responses of single V4 neurons in awake monkeys to a set of two dimensional shapes presented in two different colors. For each neuron, we chose two colors that were visually distinct and that evoked reliable and different responses. Across neurons, the correlation coefficient between responses in the two colors ranged from -0.03 to 0.93 (median 0.54). Neurons with highly consistent shape responses, i.e., high correlation coefficients, showed greater dispersion in their responses to the different shapes, i.e., greater shape selectivity, and also tended to have less eccentric receptive field locations; among shape-selective neurons, shape consistency ranged from 0.16 to 0.93 (median 0.63). Consistency of shape responses was independent of the physical difference between the stimulus colors used and the strength of neuronal color tuning. Finally, we found that our measurement of shape response consistency was strongly influenced by the number of stimulus repeats: consistency estimates based on fewer than 10 repeats were substantially underestimated. In conclusion, our results suggest that neurons that are likely to contribute to shape perception and discrimination exhibit shape responses that are largely consistent across colors, facilitating the use of simpler algorithms for decoding shape information from V4 neuronal populations. PMID- 22673325 TI - Sphingosine 1-phosphate receptor 2 antagonist JTE-013 increases the excitability of sensory neurons independently of the receptor. AB - Previously we demonstrated that sphingosine 1-phosphate receptor 1 (S1PR(1)) played a prominent, but not exclusive, role in enhancing the excitability of small-diameter sensory neurons, suggesting that other S1PRs can modulate neuronal excitability. To examine the potential role of S1PR(2) in regulating neuronal excitability we used the established selective antagonist of S1PR(2), JTE-013. Here we report that exposure to JTE-013 alone produced a significant increase in excitability in a time- and concentration-dependent manner in 70-80% of recorded neurons. Internal perfusion of sensory neurons with guanosine 5'-O-(2 thiodiphosphate) (GDP-beta-S) via the recording pipette inhibited the sensitization produced by JTE-013 as well as prostaglandin E(2). Pretreatment with pertussis toxin or the selective S1PR(1) antagonist W146 blocked the sensitization produced by JTE-013. These results indicate that JTE-013 might act as an agonist at other G protein-coupled receptors. In neurons that were sensitized by JTE-013, single-cell RT-PCR studies demonstrated that these neurons did not express the mRNA for S1PR(2). In behavioral studies, injection of JTE-013 into the rat's hindpaw produced a significant increase in the mechanical sensitivity in the ipsilateral, but not contralateral, paw. Injection of JTE-013 did not affect the withdrawal latency to thermal stimulation. Thus JTE-013 augments neuronal excitability independently of S1PR(2) by unknown mechanisms that may involve activation of other G protein-coupled receptors such as S1PR(1). Clearly, further studies are warranted to establish the causal nature of this increased sensitivity, and future studies of neuronal function using JTE-013 should be interpreted with caution. PMID- 22673326 TI - The interaction of postural and voluntary strategies for stability in Parkinson's disease. AB - This study assessed the effects of stability constraints of a voluntary task on postural responses to an external perturbation in subjects with Parkinson's disease (PD) and healthy elderly participants. Eleven PD subjects and twelve control subjects were perturbed with backward surface translations while standing and performing two versions of a voluntary task: holding a tray with a cylinder placed with the flat side down [low constraint (LC)] or with the rolling, round side down [high constraint (HC)]. Participants performed alternating blocks of LC and HC trials. PD participants accomplished the voluntary task as well as control subjects, showing slower tray velocity in the HC condition compared with the LC condition. However, the latency of postural responses was longer in the HC condition only for control subjects. Control subjects presented different patterns of hip-shoulder coordination as a function of task constraint, whereas PD subjects had a relatively invariant pattern. Initiating the experiment with the HC task led to 1) decreased postural stability in PD subjects only and 2) reduced peak hip flexion in control subjects only. These results suggest that PD impairs the capacity to adapt postural responses to constraints imposed by a voluntary task. PMID- 22673328 TI - Motion-defined contour processing in the early visual cortex. AB - From our daily experience, it is very clear that relative motion cues can contribute to correctly identifying object boundaries and perceiving depth. Motion-defined contours are not only generated by the motion of objects in a scene but also by the movement of an observer's head and body (motion parallax). However, the neural mechanism involved in detecting these contours is still unknown. To explore this mechanism, we extracellularly recorded visual responses of area 18 neurons in anesthetized and paralyzed cats. The goal of this study was to determine if motion-defined contours could be detected by neurons that have been previously shown to detect luminance-, texture-, and contrast-defined contours cue invariantly. Motion-defined contour stimuli were generated by modulating the velocity of high spatial frequency sinusoidal luminance gratings (carrier gratings) by a moving squarewave envelope. The carrier gratings were outside the luminance passband of a neuron, such that presence of the carrier alone within the receptive field did not elicit a response. Most neurons that responded to contrast-defined contours also responded to motion-defined contours. The orientation and direction selectivity of these neurons for motion-defined contours was similar to that of luminance gratings. A given neuron also exhibited similar selectivity for the spatial frequency of the carrier gratings of contrast and motion-defined contours. These results suggest that different second-order contours are detected in a form-cue invariant manner, through a common neural mechanism in area 18. PMID- 22673327 TI - Frontal eye field microstimulation induces task-dependent gamma oscillations in the lateral intraparietal area. AB - Macaque frontal eye fields (FEF) and the lateral intraparietal area (LIP) are high-level oculomotor control centers that have been implicated in the allocation of spatial attention. Electrical microstimulation of macaque FEF elicits functional magnetic resonance imaging (fMRI) activations in area LIP, but no study has yet investigated the effect of FEF microstimulation on LIP at the single-cell or local field potential (LFP) level. We recorded spiking and LFP activity in area LIP during weak, subthreshold microstimulation of the FEF in a delayed-saccade task. FEF microstimulation caused a highly time- and frequency specific, task-dependent increase in gamma power in retinotopically corresponding sites in LIP: FEF microstimulation produced a significant increase in LIP gamma power when a saccade target appeared and remained present in the LIP receptive field (RF), whereas less specific increases in alpha power were evoked by FEF microstimulation for saccades directed away from the RF. Stimulating FEF with weak currents had no effect on LIP spike rates or on the gamma power during memory saccades or passive fixation. These results provide the first evidence for task-dependent modulations of LFPs in LIP caused by top-down stimulation of FEF. Since the allocation and disengagement of spatial attention in visual cortex have been associated with increases in gamma and alpha power, respectively, the effects of FEF microstimulation on LIP are consistent with the known effects of spatial attention. PMID- 22673329 TI - Force encoding in stick insect legs delineates a reference frame for motor control. AB - The regulation of forces is integral to motor control. However, it is unclear how information from sense organs that detect forces at individual muscles or joints is incorporated into a frame of reference for motor control. Campaniform sensilla are receptors that monitor forces by cuticular strains. We studied how loads and muscle forces are encoded by trochanteral campaniform sensilla in stick insects. Forces were applied to the middle leg to emulate loading and/or muscle contractions. Selective sensory ablations limited activities recorded in the main leg nerve to specific receptor groups. The trochanteral campaniform sensilla consist of four discrete groups. We found that the dorsal groups (Groups 3 and 4) encoded force increases and decreases in the plane of movement of the coxo trochanteral joint. Group 3 receptors discharged to increases in dorsal loading and decreases in ventral load. Group 4 showed the reverse directional sensitivities. Vigorous, directional responses also occurred to contractions of the trochanteral depressor muscle and to forces applied at the muscle insertion. All sensory discharges encoded the amplitude and rate of loading or muscle force. Stimulation of the receptors produced reflex effects in the depressor motoneurons that could reverse in sign during active movements. These data, in conjunction with findings of previous studies, support a model in which the trochanteral receptors function as an array that can detect forces in all directions relative to the intrinsic plane of leg movement. The array could provide requisite information about forces and simplify the control and adaptation of posture and walking. PMID- 22673330 TI - A-current and type I/type II transition determine collective spiking from common input. AB - The mechanisms and impact of correlated, or synchronous, firing among pairs and groups of neurons are under intense investigation throughout the nervous system. A ubiquitous circuit feature that can give rise to such correlations consists of overlapping, or common, inputs to pairs and populations of cells, leading to common spike train responses. Here, we use computational tools to study how the transfer of common input currents into common spike outputs is modulated by the physiology of the recipient cells. We focus on a key conductance, g(A), for the A type potassium current, which drives neurons between "type II" excitability (low g(A)), and "type I" excitability (high g(A)). Regardless of g(A), cells transform common input fluctuations into a tendency to spike nearly simultaneously. However, this process is more pronounced at low g(A) values. Thus, for a given level of common input, type II neurons produce spikes that are relatively more correlated over short time scales. Over long time scales, the trend reverses, with type II neurons producing relatively less correlated spike trains. This is because these cells' increased tendency for simultaneous spiking is balanced by an anticorrelation of spikes at larger time lags. These findings extend and interpret prior findings for phase oscillators to conductance-based neuron models that cover both oscillatory (superthreshold) and subthreshold firing regimes. We demonstrate a novel implication for neural signal processing: downstream cells with long time constants are selectively driven by type I cell populations upstream and those with short time constants by type II cell populations. Our results are established via high-throughput numerical simulations and explained via the cells' filtering properties and nonlinear dynamics. PMID- 22673332 TI - Absence of effects of contralateral group I muscle afferents on presynaptic inhibition of Ia terminals in humans and cats. AB - Crossed effects from group I afferents on reflex excitability and their mechanisms of action are not yet well understood. The current view is that the influence is weak and takes place indirectly via oligosynaptic pathways. We examined possible contralateral effects from group I afferents on presynaptic inhibition of Ia terminals in humans and cats. In resting and seated human subjects the soleus (SO) H-reflex was conditioned by an electrical stimulus to the ipsilateral common peroneal nerve (CPN) to assess the level of presynaptic inhibition (PSI_control). A brief conditioning vibratory stimulus was applied to the triceps surae tendon at the contralateral side (to activate preferentially Ia muscle afferents). The amplitude of the resulting H-reflex response (PSI_conditioned) was compared to the H-reflex under PSI_control, i.e., without the vibration. The interstimulus interval between the brief vibratory stimulus and the electrical shock to the CPN was -60 to 60 ms. The H-reflex conditioned by both stimuli did not differ from that conditioned exclusively by the ipsilateral CPN stimulation. In anesthetized cats, bilateral monosynaptic reflexes (MSRs) in the left and right L(7) ventral roots were recorded simultaneously. Conditioning stimulation applied to the contralateral group I posterior biceps and semitendinosus (PBSt) afferents at different time intervals (0-120 ms) did not have an effect on the ipsilateral gastrocnemius/soleus (GS) MSR. An additional experimental paradigm in the cat using contralateral tendon vibration, similar to that conducted in humans, was also performed. No significant differences between GS-MSRs conditioned by ipsilateral PBSt stimulus alone and those conditioned by both ipsilateral PBSt stimulus and contralateral tendon vibration were detected. The present results strongly suggest an absence of effects from contralateral group I fibers on the presynaptic mechanism of MSR modulation in relaxed humans and anesthetized cats. PMID- 22673331 TI - A point process framework for modeling electrical stimulation of the auditory nerve. AB - Model-based studies of responses of auditory nerve fibers to electrical stimulation can provide insight into the functioning of cochlear implants. Ideally, these studies can identify limitations in sound processing strategies and lead to improved methods for providing sound information to cochlear implant users. To accomplish this, models must accurately describe spiking activity while avoiding excessive complexity that would preclude large-scale simulations of populations of auditory nerve fibers and obscure insight into the mechanisms that influence neural encoding of sound information. In this spirit, we develop a point process model of individual auditory nerve fibers that provides a compact and accurate description of neural responses to electric stimulation. Inspired by the framework of generalized linear models, the proposed model consists of a cascade of linear and nonlinear stages. We show how each of these stages can be associated with biophysical mechanisms and related to models of neuronal dynamics. Moreover, we derive a semianalytical procedure that uniquely determines each parameter in the model on the basis of fundamental statistics from recordings of single fiber responses to electric stimulation, including threshold, relative spread, jitter, and chronaxie. The model also accounts for refractory and summation effects that influence the responses of auditory nerve fibers to high pulse rate stimulation. Throughout, we compare model predictions to published physiological data of response to high and low pulse rate stimulation. We find that the model, although constructed to fit data from single and paired pulse experiments, can accurately predict responses to unmodulated and modulated pulse train stimuli. We close by performing an ideal observer analysis of simulated spike trains in response to sinusoidally amplitude modulated stimuli and find that carrier pulse rate does not affect modulation detection thresholds. PMID- 22673333 TI - Integration of cortical and pallidal inputs in the basal ganglia-recipient thalamus of singing birds. AB - The basal ganglia-recipient thalamus receives inhibitory inputs from the pallidum and excitatory inputs from cortex, but it is unclear how these inputs interact during behavior. We recorded simultaneously from thalamic neurons and their putative synaptically connected pallidal inputs in singing zebra finches. We find, first, that each pallidal spike produces an extremely brief (~5 ms) pulse of inhibition that completely suppresses thalamic spiking. As a result, thalamic spikes are entrained to pallidal spikes with submillisecond precision. Second, we find that the number of thalamic spikes that discharge within a single pallidal interspike interval (ISI) depends linearly on the duration of that interval but does not depend on pallidal activity prior to the interval. In a detailed biophysical model, our results were not easily explained by the postinhibitory "rebound" mechanism previously observed in anesthetized birds and in brain slices, nor could most of our data be characterized as "gating" of excitatory transmission by inhibitory pallidal input. Instead, we propose a novel "entrainment" mechanism of pallidothalamic transmission that highlights the importance of an excitatory conductance that drives spiking, interacting with brief pulses of pallidal inhibition. Building on our recent finding that cortical inputs can drive syllable-locked rate modulations in thalamic neurons during singing, we report here that excitatory inputs affect thalamic spiking in two ways: by shortening the latency of a thalamic spike after a pallidal spike and by increasing thalamic firing rates within individual pallidal ISIs. We present a unifying biophysical model that can reproduce all known modes of pallidothalamic transmission--rebound, gating, and entrainment--depending on the amount of excitation the thalamic neuron receives. PMID- 22673334 TI - Muscle spindle responses to horizontal support surface perturbation in the anesthetized cat: insights into the role of autogenic feedback in whole body postural control. AB - Intact cats and humans respond to support surface perturbations with broadly tuned, directionally sensitive muscle activation. These muscle responses are further sensitive to initial stance widths (distance between feet) and perturbation velocity. The sensory origins driving these responses are not known, and conflicting hypotheses are prevalent in the literature. We hypothesize that the direction-, stance-width-, and velocity-sensitive muscle response during support surface perturbations is driven largely by rapid autogenic proprioceptive pathways. The primary objective of this study was to obtain direct evidence for our hypothesis by establishing that muscle spindle receptors in the intact limb can provide appropriate information to drive the muscle response to whole body postural perturbations. Our second objective was to determine if spindle recordings from the intact limb generate the heightened sensitivity to small perturbations that has been reported in isolated muscle experiments. Maintenance of this heightened sensitivity would indicate that muscle spindles are highly proficient at detecting even small disturbances, suggesting they can provide efficient feedback about changing postural conditions. We performed intraaxonal recordings from muscle spindles in anesthetized cats during horizontal, hindlimb perturbations. We indeed found that muscle spindle afferents in the intact limb generate broadly tuned but directionally sensitive activation patterns. These afferents were also sensitive to initial stance widths and perturbation velocities. Finally, we found that afferents in the intact limb have heightened sensitivity to small perturbations. We conclude that muscle spindle afferents provide an array of important information about biomechanics and perturbation characteristics highlighting their potential importance in generating appropriate muscular response during a postural disturbance. PMID- 22673335 TI - Protein arginine methyltransferase 6-dependent gene expression and splicing: association with breast cancer outcomes. AB - Protein arginine methyltransferase-6 (PRMT6) regulates steroid-dependent transcription and alternative splicing and is implicated in endocrine system development and function, cell death, cell cycle, gene expression and cancer. Despite its role in these processes, little is known about its function and cellular targets in breast cancer. To identify novel gene targets regulated by PRMT6 in breast cancer cells, we used a combination of small interfering RNA and exon-specific microarray profiling in vitro coupled to in vivo validation in normal breast and primary human breast tumours. This approach, which allows the examination of genome-wide changes in individual exon usage and total transcript levels, demonstrated that PRMT6 knockdown significantly affected i) the transcription of 159 genes and ii) alternate splicing of 449 genes. The PRMT6 dependent transcriptional and alternative splicing targets identified in vitro were validated in human breast tumours. Using the list of genes differentially expressed between normal and PRMT6 knockdown cells, we generated a PRMT6 dependent gene expression signature that provides an indication of PRMT6 dysfunction in breast cancer cells. Interrogation of several well-studied breast cancer microarray expression datasets with the PRMT6 gene expression signature demonstrated that PRMT6 dysfunction is associated with better overall relapse free and distant metastasis-free survival in the oestrogen receptor (ER (ESR1)) breast cancer subgroup. These results suggest that dysregulation of PRMT6 dependent transcription and alternative splicing may be involved in breast cancer pathophysiology and the molecular consequences identifying a unique and informative biomarker profile. PMID- 22673336 TI - Combination of sorafenib and everolimus impacts therapeutically on adrenocortical tumor models. AB - Treatment options are insufficient in patients with adrenocortical carcinoma (ACC). Based on the efficacy of sorafenib, a tyrosine kinase inhibitor, and everolimus, an inhibitor of the mammalian target of rapamycin in tumors of different histotype, we aimed at testing these drugs in adrenocortical cancer models. The expression of vascular endothelial growth factor and its receptors (VEGFR1-2) was studied in 18 ACCs, 33 aldosterone-producing adenomas, 12 cortisol producing adenomas, and six normal adrenal cortex by real-time PCR and immunohistochemistry and by immunoblotting in SW13 and H295R cancer cell lines. The effects of sorafenib and everolimus, alone or in combination, were tested on primary adrenocortical cultures and SW13 and H295R cells by evaluating cell viability and apoptosis in vitro and tumor growth inhibition of tumor cell line xenografts in immunodeficient mice in vivo. VEGF and VEGFR1-2 were detected in all samples and appeared over-expressed in two-thirds of ACC specimens. Dose dependent inhibition of cell viability was observed particularly in SW13 cells after 24 h treatment with either drug; drug combination produced markedly synergistic growth inhibition. Increasing apoptosis was observed in tumor cells treated with the drugs, particularly with sorafenib. Finally, a significant mass reduction and increased survival were observed in SW13 xenograft model undergoing treatment with the drugs in combination. Our data suggest that an autocrine VEGF loop may exist within ACC. Furthermore, a combination of molecularly targeted agents may have both antiangiogenic and direct antitumor effects and thus could represent a new therapeutic tool for the treatment of ACC. PMID- 22673337 TI - Removal of antibiotics from water using sewage sludge- and waste oil sludge derived adsorbents. AB - Sewage sludge- and waste oil sludge-derived materials were tested as adsorbents of pharmaceuticals from diluted water solutions. Simultaneous retention of eleven antibiotics plus two anticonvulsants was examined via batch adsorption experiments. Virgin and exhausted adsorbents were examined via thermal and FTIR analyses to elucidate adsorption mechanisms. Maximum adsorption capacities for the 6 materials tested ranged from 80 to 300 mg/g, comparable to the adsorption capacities of antibiotics on various activated carbons (200-400 mg/g) reported in the literature. The performance was linked to surface reactivity, polarity and porosity. A large volume of pores similar in size to the adsorbate molecules with hydrophobic carbon-based origin of pore walls was indicated as an important factor promoting the separation process. Moreover, the polar surface of an inorganic phase in the adsorbents attracted the functional groups of target molecules. The presence of reactive alkali metals promoted reaction with acidic groups, formation of salts and their precipitation in the pore system. PMID- 22673338 TI - Effects of humic acid and electrolytes on photocatalytic reactivity and transport of carbon nanoparticle aggregates in water. AB - The effects of naturally occurring macromolecules such as humic acid (HA) and electrolytes on four fullerene nanoparticle suspensions (i.e., C(60), C(60)(OH)(24), single- and multiwall carbon nanotubes) were explored with respect to: (1) characteristics of nanoparticle aggregates, (2) transport of the aggregates through a silica porous media, and (3) production of reactive oxygen species (ROS) from the photosensitized fullerene aggregates. The presence of HA and salts increased the size of aggregates and relative hydrophobicity associated with transport through silica beads, while decreasing ROS production. These data illustrate the importance that transformation of engineered nanomaterials (ENMs) through interactions with aquatic solutes may have in altering the environmental behavior of nanomaterials. PMID- 22673339 TI - Temporal and spatial distributions of ammonia-oxidizing archaea and bacteria and their ratio as an indicator of oligotrophic conditions in natural wetlands. AB - Ammonia-oxidizing organisms play an important role in wetland water purification and nitrogen cycling. We determined soil nitrification rates and investigated the seasonal and spatial distributions of ammonia-oxidizing archaea (AOA) and ammonia oxidizing bacteria (AOB) in three freshwater wetlands by using specific primers targeting the amoA genes of AOA and AOB and real-time quantitative polymerase chain reaction (qPCR). The nitrifying potentials of wetland soils ranged from 1.4 to 4.0 MUg g(-1) day(-1). The specific rates of ammonia oxidation activity by AOA and AOB at the Bee Hollow wetlands were 1.9 fmol NH(3) cell(-1) day(-1) and 36.8 fmol NH(3) cell(-1) day(-1), respectively. Soil nitrification potential was positively correlated with both archaeal and bacterial amoA abundance. However, the gene copies of AOA amoA were higher than those of AOB amoA by at least an order of magnitude in wetland soils and water in both summer and winter over a three year study period. AOB were more sensitive to low temperature than AOA. The amoA gene copy ratios of AOA to AOB in top soils (0-10 cm) ranged from 19 +/- 4 to 100 +/- 11 among the wetland sites. In contrast, the ratio of the wetland boundary soil was 10 +/- 2, which was significantly lower than that of the wetland soils (P < 0.001). The NH(4)(+)-N concentrations in wetland water were lower than 2 mg/L throughout the study. The results suggest that ammonium concentration is a major factor influencing AOA and AOB population in wetlands, although other factors such as temperature, dissolved oxygen, and soil organic matter are involved. AOA are more persistent and more abundant than AOB in the nutrient-depleted oligotrophic wetlands. Therefore, ratio of AOA amoA gene copies to AOB amoA gene copies may serve as a new biological indicator for wetland condition assessment and wetland restoration applications. PMID- 22673340 TI - Fate of As(V)-treated nano zero-valent iron: determination of arsenic desorption potential under varying environmental conditions by phosphate extraction. AB - Nano zero-valent iron (NZVI) offers a promising approach for arsenic remediation, but the spent NZVI with elevated arsenic content could arouse safety concerns. This study investigated the fate of As(V)-treated NZVI (As-NZVI), by examining the desorption potential of As under varying conditions. The desorption kinetics of As from As-NZVI as induced by phosphate was well described by a biphasic rate model. The effects of As(V)/NZVI mass ratio, pH, and aging time on arsenic desorption from As-NZVI by phosphate were investigated. Less arsenic desorption was observed at lower pH or higher As(V)/NZVI mass ratio, where stronger complexes (bidentate) formed between As(V) and NZVI corrosion products as indicated by FTIR analysis. Compared with the fresh As-NZVI, the amount of phosphate-extractable As significantly decreased in As-NZVI aged for 30 or 60 days. The results of the sequential extraction experiments demonstrated that a larger fraction of As was sorbed in the crystalline phases after aging, making it less susceptible to phosphate displacement. However, at pH 9, a slightly higher proportion of phosphate-extractable As was observed in the 60-day sample than in the 30-day sample. XPS results revealed the transformation of As(V) to more easily desorbed As(III) during aging and a higher As(III)/As(V) ratio in the 60 day sample at pH 9, which might have resulted in the higher desorption. PMID- 22673341 TI - Microbial quality assessment of household greywater. AB - A monitoring program was undertaken to assess the microbial quality of greywater collected from 93 typical households in Melbourne, Australia. A total of 185 samples, comprising 75 washing machine wash, 74 washing machine rinse and 36 bathroom samples were analysed for the faecal indicator Escherichia coli. Of these, 104 were also analysed for genetic markers of pathogenic E coli and 111 for norovirus (genogroups GI and GII), enterovirus and rotavirus using RT-PCR. Enteric viruses were detected in 20 out of the 111 (18%) samples comprising 16 washing machine wash water and 4 bathroom samples. Eight (7%) samples were positive for enterovirus, twelve (11%) for norovirus genogroup GI, one (1%) for norovirus genogroup GII and another (1%) for rotavirus. Two washing machine samples contained more than one virus. Typical pathogenic E. coli were detected in 3 out of 104 (3%) samples and atypical enteropathogenic E. coli in 11 (11%) of samples. Levels of indicator E. coli were highly variable and the presence of E. coli was not associated with the presence of human enteric viruses in greywater. There was also little correlation between reported gastrointestinal illness in households and detection of pathogens in greywater. PMID- 22673342 TI - Antiscalant removal in accelerated desupersaturation of RO concentrate via chemically-enhanced seeded precipitation (CESP). AB - An experimental study was carried out to demonstrate and quantify the feasibility of antiscalant (AS) removal from brackish water RO concentrate of high gypsum scaling propensity via lime treatment prior to seeded gypsum precipitation. Based on studies with model solutions, it was shown that sufficient AS removal (up to ~90%) from RO concentrate is feasible via a lime treatment step (at a dose significantly lower than that required for conventional lime softening) to enable effective subsequent seeded gypsum precipitation. This two-step chemically enhanced seeded precipitation (CESP) treatment of primary RO concentrate is suitable as an intermediate concentrate demineralization (ICD) stage for high recovery desalting employing secondary RO desalination. Analysis of gypsum precipitation and lime treatment kinetic data suggests that, after adequate CaCO(3) precipitation has been induced for effective AS scavenging, CaSO(4) desupersaturation can be achieved via seeded gypsum precipitation without retardation due to seed poisoning by AS. Also, the lime dose required to prevent seed poisoning during subsequent gypsum desupersaturation via seeded gypsum precipitation can be adequately assessed with a precipitation kinetics model that considers AS seed poisoning based on a Langmuir adsorption isotherm. The degree of AS removal after lime treatment increased linearly with the logarithm of the single lime dose additions. Staged lime dosing (i.e., multiple lime additions), however, removed a higher degree of AS relative to an equivalent single lime dose addition since a higher driving force for CaCO(3) precipitation could be maintained over the course of the lime treatment period. PMID- 22673343 TI - Biodegradation of triclosan by a wastewater microorganism. AB - Triclosan, a synthetic antimicrobial agent, has been considered as an emerging environmental contaminant. Here we reported a triclosan-degrading wastewater bacterial isolate, Sphingopyxis strain KCY1, capable of dechlorinating triclosan with a stoichiometric release of chloride. The stain can degrade diphenyl ether but not 2,4,4'-tribromodiphenyl ether and 2,2',4,4'-tetrabromodiphenyl ether, despite all these three compounds are structurally similar to triclosan. While strain KCY1 was unable to grow on triclosan and catechol, it could grow with glucose, sodium succinate, sodium acetate, and phenol. When grown with complex nutrient medium containing a trace amount of triclosan (as low as 5 MUg/L), the strain could retain its degradation ability toward triclosan. The maximum specific triclosan degradation rate (q(m)) and the half-velocity constant (K(m)) are 0.13 mg-triclosan/mg-protein/day and 2.8 mg-triclosan/L, respectively. As triclosan degradation progressed, five metabolites were identified and these metabolites continue to transform into non-chlorinated end products, which was supported by a sharp drop in androgenic potential. The activity of catechol 2,3 dioxygenase in the cell extract was detected. No triclosan degradation was observed in the presence of 3-fluorocatechol, an inhibitor of meta-cleavage enzyme, suggesting that triclosan degradation proceed via meta-cleavage pathway. Based on all the observations, a degradation pathway for triclosan by strain KCY1 was proposed. PMID- 22673344 TI - The burden of drinking water-associated cryptosporidiosis in China: the large contribution of the immunodeficient population identified by quantitative microbial risk assessment. AB - A comprehensive quantitative microbial risk assessment (QMRA) of Cryptosporidium infection, considering pathogen removal efficiency, different exposure pathways and different susceptible subpopulations, was performed based on the result of a survey of source water from 66 waterworks in 33 major cities across China. The Cryptosporidium concentrations in source water were 0-6 oocysts/10 L, with a mean value of 0.7 oocysts/10 L. The annual diarrhea morbidity caused by Cryptosporidium in drinking water was estimated to be 2701 (95% confidence interval (CI): 138-9381) cases per 100,000 immunodeficient persons and 148 (95% CI: 1-603) cases per 100,000 immunocompetent persons, giving an overall rate of 149.0 (95% CI: 1.3-606.4) cases per 100,000 population. The cryptosporidiosis burden associated with drinking water treated with the conventional process was calculated to be 8.31 * 10(-6) (95% CI: 0.34-30.93 * 10(-6)) disability-adjusted life years (DALYs) per person per year, which was higher than the reference risk level suggested by the World Health Organization (WHO), but lower than that suggested by the United States Environmental Protection Agency (USEPA). Sixty-six percent of the total health burden due to cryptosporidiosis that occurred in the immunodeficient subpopulation, and 90% of the total DALYs was attributed to adults aged 15-59 years. The sensitivity analysis highlighted the great importance of stability of the treatment process and the importance of watershed protection. The results of this study will be useful in better evaluating and reducing the burden of Cryptosporidium infection. PMID- 22673345 TI - Measuring and mitigating inhibition during quantitative real time PCR analysis of viral nucleic acid extracts from large-volume environmental water samples. AB - Naturally-occurring inhibitory compounds are a major concern during qPCR and RT qPCR analysis of environmental samples, particularly large volume water samples. Here, a standardized method for measuring and mitigating sample inhibition in environmental water concentrates is described. Specifically, the method 1) employs a commercially available standard RNA control; 2) defines inhibition by the change in the quantification cycle (C(q)) of the standard RNA control when added to the sample concentrate; and 3) calculates a dilution factor using a mathematical formula applied to the change in C(q) to indicate the specific volume of nuclease-free water necessary to dilute the effect of inhibitors. The standardized inhibition method was applied to 3,193 large-volume water (surface, groundwater, drinking water, agricultural runoff, sewage) concentrates of which 1,074 (34%) were inhibited. Inhibition level was not related to sample volume. Samples collected from the same locations over a one to two year period had widely variable inhibition levels. The proportion of samples that could have been reported as false negatives if inhibition had not been mitigated was between 0.3% and 71%, depending on water source. These findings emphasize the importance of measuring and mitigating inhibition when reporting qPCR results for viral pathogens in environmental waters to minimize the likelihood of reporting false negatives and under-quantifying virus concentration. PMID- 22673346 TI - The use of Bassia indica for salt phytoremediation in constructed wetlands. AB - The treatment and reuse of wastewater in constructed wetlands offers a low-cost, environmentally-friendly alternative for common engineered systems. Salinity in treated wastewater is often increased, especially in arid and semi-arid areas, and may harm crops irrigated from wetlands. We have strong evidence that halophyte plants are able to reduce the salinity of wastewater by accumulating salts in their tissues. Bassia indica is an annual halophyte with unique adaptations for salt tolerance. We performed three experiments to evaluate the capability of B. indica for salt phytoremediation as follows: a hydroponic system with mixed salt solutions, a recirculated vertical flow constructed wetland (RVFCW) with domestic wastewater, and a vertical flow constructed wetland (VFCW) for treating goat farm effluents. B. Indica plants developed successfully in all three systems and reduced the effluent salinity by 20-60% in comparison with unplanted systems or systems planted with other wetland plants. Salinity reduction was attributed to the accumulation of salts, mainly Na and K, in the leaves. Our experiments were carried out on an operative scale, suggesting a novel treatment for green desalination in constructed wetlands by salt phytoremediation in desert regions and other ecosystems. PMID- 22673347 TI - Origin of fecal contamination in waters from contrasted areas: stanols as Microbial Source Tracking markers. AB - Improving the microbiological quality of coastal and river waters relies on the development of reliable markers that are capable of determining sources of fecal pollution. Recently, a principal component analysis (PCA) method based on six stanol compounds (i.e. 5beta-cholestan-3beta-ol (coprostanol), 5beta-cholestan 3alpha-ol (epicoprostanol), 24-methyl-5alpha-cholestan-3beta-ol (campestanol), 24 ethyl-5alpha-cholestan-3beta-ol (sitostanol), 24-ethyl-5beta-cholestan-3beta-ol (24-ethylcoprostanol) and 24-ethyl-5beta-cholestan-3alpha-ol (24 ethylepicoprostanol)) was shown to be suitable for distinguishing between porcine and bovine feces. In this study, we tested if this PCA method, using the above six stanols, could be used as a tool in "Microbial Source Tracking (MST)" methods in water from areas of intensive agriculture where diffuse fecal contamination is often marked by the co-existence of human and animal sources. In particular, well defined and stable clusters were found in PCA score plots clustering samples of "pure" human, bovine and porcine feces along with runoff and diluted waters in which the source of contamination is known. A good consistency was also observed between the source assignments made by the 6-stanol-based PCA method and the microbial markers for river waters contaminated by fecal matter of unknown origin. More generally, the tests conducted in this study argue for the addition of the PCA method based on six stanols in the MST toolbox to help identify fecal contamination sources. The data presented in this study show that this addition would improve the determination of fecal contamination sources when the contamination levels are low to moderate. PMID- 22673348 TI - Predicting the settling velocity of flocs formed in water treatment using multiple fractal dimensions. AB - Here we introduce a distribution of floc fractal dimensions as opposed to a single fractal dimension value into the floc settling velocity model developed in earlier studies. The distribution of fractal dimensions for a single floc size was assumed to cover a range from 1.9 to 3.0. This range was selected based on the theoretically determined fractal dimensions for diffusion-limited and cluster cluster aggregation. These two aggregation mechanisms are involved in the formation of the lime softening flocs analyzed in this study. Fractal dimensions were generated under the assumption that a floc can have any value of normally distributed fractal dimensions ranging from 1.9-3.0. A range of settling velocities for a single floc size was calculated based on the distribution of fractal dimensions. The assumption of multiple fractal dimensions for a single floc size resulted in a non-unique relationship between the floc size and the floc settling velocity, i.e., several different settling velocities were calculated for one floc size. The settling velocities calculated according to the model ranged from 0 to 10 mm/s (average 2.22 mm/s) for the majority of flocs in the size range of 1-250 MUm (average 125 MUm). The experimentally measured settling velocities of flocs ranged from 0.1 to 7.1 mm/s (average 2.37 mm/s) for the flocs with equivalent diameters from 10 MUm to 260 MUm (average 124 MUm). Experimentally determined floc settling velocities were predicted well by the floc settling model incorporating distributions of floc fractal dimensions calculated based on the knowledge of the mechanisms of aggregation, i.e., cluster cluster aggregation and diffusion-limited aggregation. PMID- 22673349 TI - Association between thyroid stimulating hormone receptor gene intron polymorphisms and autoimmune thyroid disease in a Chinese Han population. AB - Autoimmune thyroid disease (AITD) is a multifactorial disease with a genetic susceptibility and environmental factors. The thyroid stimulating hormone receptor gene (TSHR) which is expressed on the surface of the thyroid epithelial cell is thought to be the main auto-antigen and a significant candidate for genetic susceptibility to AITD. This case-control study aimed at evaluating the association between single nucleotide polymorphisms (SNP) of TSHR and AITD in a Chinese Han population. We recruited 404 patients with Graves' disease (GD), 230 patients with Hashimoto's thyroiditis (HT) and 242 healthy controls. The Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometer (MALDI-TOF MS) Platform was used to detect five SNPs (rs179247, rs12101255, rs2268475, rs1990595, and rs3783938) in TSHR gene. The frequencies of allele T and TT genotype of rs12101255 in GD patients were significantly increased compared with those of the controls (P=0.004/0.015, OR=1.408/1.446). The allele A frequency of rs3783938 was greater in HT patients than in the controls (P=0.025, OR=1.427). The AT haplotype (rs179247-rs12101255) was associated with an increased risk of GD (P=0.010, OR=1.368). The allele A of rs179247 was associated with ophthalmopathy in GD patients. These data suggest that the polymorphisms of rs12101255 and rs3783938 are associated with GD and HT, respectively. PMID- 22673350 TI - Cleft palate associated with cervico-facial teratoma: report of two cases and review of the literature. AB - We report two original cases of association of cleft palate and lateral cervico facial teratoma. We discuss the embryological explanation. The first child presented a cleft palate associated with two cervico-facial localisations of teratoma. The other had Pierre Robin sequence associated with lateropharyngeal teratoma with an extra sub maxillary localisation. Most reported cases were of midline teratomas, leading different authors to advance a mechanical origin to the cleft. Our cases are different: we could hardly find reported cases of associate lateral tumours and cleft palate, which would suggest two different embryologic mechanisms, or at least a combination of more complicated phenomenons. PMID- 22673351 TI - Parallel evolution of angiosperm colour signals: common evolutionary pressures linked to hymenopteran vision. AB - Flowering plants in Australia have been geographically isolated for more than 34 million years. In the Northern Hemisphere, previous work has revealed a close fit between the optimal discrimination capabilities of hymenopteran pollinators and the flower colours that have most frequently evolved. We collected spectral data from 111 Australian native flowers and tested signal appearance considering the colour discrimination capabilities of potentially important pollinators. The highest frequency of flower reflectance curves is consistent with data reported for the Northern Hemisphere. The subsequent mapping of Australian flower reflectances into a bee colour space reveals a very similar distribution of flower colour evolution to the Northern Hemisphere. Thus, flowering plants in Australia are likely to have independently evolved spectral signals that maximize colour discrimination by hymenoptera. Moreover, we found that the degree of variability in flower coloration for particular angiosperm species matched the range of reflectance colours that can only be discriminated by bees that have experienced differential conditioning. This observation suggests a requirement for plasticity in the nervous systems of pollinators to allow generalization of flowers of the same species while overcoming the possible presence of non rewarding flower mimics. PMID- 22673352 TI - Evaluating the role of contracting and expanding rainforest in initiating cycles of speciation across the Isthmus of Panama. AB - Climatic and geological changes across time are presumed to have shaped the rich biodiversity of tropical regions. However, the impact climatic drying and subsequent tropical rainforest contraction had on speciation has been controversial because of inconsistent palaeoecological and genetic data. Despite the strong interest in examining the role of climatic change on speciation in the Neotropics there has been few comparative studies, particularly, those that include non-rainforest taxa. We used bird species that inhabit humid or dry habitats that dispersed across the Panamanian Isthmus to characterize temporal and spatial patterns of speciation across this barrier. Here, we show that these two assemblages of birds exhibit temporally different speciation time patterns that supports multiple cycles of speciation. Evidence for these cycles is further corroborated by the finding that both assemblages consist of 'young' and 'old' species, despite dry habitat species pairs being geographically more distant than pairs of humid habitat species. The matrix of humid and dry habitats in the tropics not only allows for the maintenance of high species richness, but additionally this study suggests that these environments may have promoted speciation. We conclude that differentially expanding and contracting distributions of dry and humid habitats was probably an important contributor to speciation in the tropics. PMID- 22673353 TI - An information-theoretic approach to evaluating the size and temperature dependence of metabolic rate. AB - The effects of body mass and temperature on metabolic rate (MR) are among the most widely examined physiological relationships. Recently, these relationships have been incorporated into the metabolic theory of ecology (MTE) that links the ecology of populations, communities and ecosystems to the MR of individual organisms. The fundamental equation of MTE derives the relation between mass and MR using first principles and predicts the temperature dependence of MR based on biochemical kinetics. It is a deliberately simple, zeroth-order approximation that represents a baseline against which variation in real biological systems can be examined. In the present study, we evaluate the fundamental equation of MTE against other more parameter-rich models for MR using an information-theoretic approach to penalize the inclusion of additional parameters. Using a comparative database of MR measurements for 1359 species, from 11 groups ranging from prokaryotes to mammals, and spanning 16 orders of magnitude in mass and a 59 degrees C range in body temperature, we show that differences between taxa in the mass and temperature dependence of MR are sufficiently large as to be retained in the best model for MR despite the requirement for estimation of 22 more parameters than the fundamental equation of MTE. PMID- 22673354 TI - Location, location, location: finding a suitable home among the noise. AB - While sound is a useful cue for guiding the onshore orientation of larvae because it travels long distances underwater, it also has the potential to convey valuable information about the quality and type of the habitat at the source. Here, we provide, to our knowledge, the first evidence that settlement-stage coastal crab species can interpret and show a strong settlement and metamorphosis response to habitat-related differences in natural underwater sound. Laboratory- and field-based experiments demonstrated that time to metamorphosis in the settlement-stage larvae of common coastal crab species varied in response to different underwater sound signatures produced by different habitat types. The megalopae of five species of both temperate and tropical crabs showed a significant decrease in time to metamorphosis, when exposed to sound from their optimal settlement habitat type compared with other habitat types. These results indicate that sounds emanating from specific underwater habitats may play a major role in determining spatial patterns of recruitment in coastal crab species. PMID- 22673355 TI - Scaling of form and function in the xenarthran femur: a 100-fold increase in body mass is mitigated by repositioning of the third trochanter. AB - How animals cope with increases in body size is a key issue in biology. Here, we consider scaling of xenarthrans, particularly how femoral form and function varies to accommodate the size range between the 3 kg armadillo and its giant relative the 300 kg glyptodont. It has already been noted that femoral morphology differs between these animals and suggested that this reflects a novel adaptation to size increase in glyptodont. We test this idea by applying a finite element analysis of coronal plane forces to femoral models of these animals, simulating the stance phase in the hind limb; where the femur is subject to bending owing to longitudinal compressive as well as abduction loads on the greater trochanter. We use these models to examine the hypothesis that muscles attaching on the third trochanter (T3) can reduce this bending in the loaded femur and that the T3 forces are more effective at reducing bending in glyptodont where the T3 is situated at the level of the knee. The analysis uses traditional finite element methods to produce strain maps and examine strains at 200 points on the femur. The coordinates of these points before and after loading are also used to carry out geometric morphometric (GM) analyses of the gross deformation of the model in different loading scenarios. The results show that longitudinal compressive and abductor muscle loading increases bending in the coronal plane, and that loads applied to the T3 reduce that bending. In the glyptodont model, the T3 loads are more effective and can more readily compensate for the bending owing to longitudinal and abductor loads. This study also demonstrates the usefulness of GM methods in interpreting the results of finite element analyses. PMID- 22673356 TI - Transition from sea to land: olfactory function and constraints in the terrestrial hermit crab Coenobita clypeatus. AB - The ability to identify chemical cues in the environment is essential to most animals. Apart from marine larval stages, anomuran land hermit crabs (Coenobita) have evolved different degrees of terrestriality, and thus represent an excellent opportunity to investigate adaptations of the olfactory system needed for a successful transition from aquatic to terrestrial life. Although superb processing capacities of the central olfactory system have been indicated in Coenobita and their olfactory system evidently is functional on land, virtually nothing was known about what type of odourants are detected. Here, we used electroantennogram (EAG) recordings in Coenobita clypeatus and established the olfactory response spectrum. Interestingly, different chemical groups elicited EAG responses of opposite polarity, which also appeared for Coenobita compressus and the closely related marine hermit crab Pagurus bernhardus. Furthermore, in a two-choice bioassay with C. clypeatus, we found that water vapour was critical for natural and synthetic odourants to induce attraction or repulsion. Strikingly, also the physiological response was found much greater at higher humidity in C. clypeatus, whereas no such effect appeared in the terrestrial vinegar fly Drosophila melanogaster. In conclusion, our results reveal that the Coenobita olfactory system is restricted to a limited number of water-soluble odourants, and that high humidity is most critical for its function. PMID- 22673357 TI - A positive effect of flowers rather than eye images in a large-scale, cross cultural dictator game. AB - People often consider how their behaviour will be viewed by others, and may cooperate to avoid gaining a bad reputation. Sensitivity to reputation may be elicited by subtle social cues of being watched: previous studies have shown that people behave more cooperatively when they see images of eyes rather than control images. Here, we tested whether eye images enhance cooperation in a dictator game, using the online labour market Amazon Mechanical Turk (AMT). In contrast to our predictions and the results of most previous studies, dictators gave away more money when they saw images of flowers rather than eye images. Donations in response to eye images were not significantly different to donations under control treatments. Dictator donations varied significantly across cultures but there was no systematic variation in responses to different image types across cultures. Unlike most previous studies, players interacting via AMT may feel truly anonymous when making decisions and, as such, may not respond to subtle social cues of being watched. Nevertheless, dictators gave away similar amounts as in previous studies, so anonymity did not erase helpfulness. We suggest that eye images might only promote cooperative behaviour in relatively public settings and that people may ignore these cues when they know their behaviour is truly anonymous. PMID- 22673358 TI - Natural simian immunodeficiency virus transmission in mandrills: a family affair? AB - Understanding how pathogens spread and persist in the ecosystem is critical for deciphering the epidemiology of diseases of significance for global health and the fundamental mechanisms involved in the evolution of virulence and host resistance. Combining long-term behavioural and epidemiological data collected in a naturally infected mandrill population and a Bayesian framework, the present study investigated unknown aspects of the eco-epidemiology of simian immunodeficiency virus (SIV), the recent ancestor of HIV. Results show that, in contrast to what is expected from aggressive and sexual transmission (i.e. the two commonly accepted transmission modes for SIV), cases of SIVmnd-1 subtype were significantly correlated among related individuals (greater than 30% of the observed cases). Challenging the traditional view of SIV, this finding suggests the inheritance of genetic determinants of susceptibility to SIV and/or a role for behavioural interactions among maternal kin affecting the transmission of the virus, which would highlight the underappreciated role of sociality in the spread of infectious diseases. Outcomes of this study also provide novel insights into the role of host social structure in the evolution of pathogens. PMID- 22673359 TI - Major role of positive selection in the evolution of conservative segments of Drosophila proteins. AB - Slow evolution of conservative segments of coding and non-coding DNA is caused by the action of negative selection, which removes new mutations. However, the mode of selection that affects the few substitutions that do occur within such segments remains unclear. Here, we show that the fraction of allele replacements that were driven by positive selection, and the strength of this selection, is the highest within the conservative segments of Drosophila protein-coding genes. The McDonald-Kreitman test, applied to the data on variation in Drosophila melanogaster and in Drosophila simulans, indicates that within the most conservative protein segments, approximately 72 per cent (approx. 80%) of allele replacements were driven by positive selection, as opposed to only approximately 44 per cent (approx. 53%) at rapidly evolving segments. Data on multiple non synonymous substitutions at a codon lead to the same conclusion and additionally indicate that positive selection driving allele replacements at conservative sites is the strongest, as it accelerates evolution by a factor of approximately 40, as opposed to a factor of approximately 5 at rapidly evolving sites. Thus, random drift plays only a minor role in the evolution of conservative DNA segments, and those relatively rare allele replacements that occur within such segments are mostly driven by substantial positive selection. PMID- 22673361 TI - Effect of work stressors, personal strain, and coping resources on burnout in Chinese medical professionals: a structural equation model. AB - The present study analyzes the effect of work stressors, personal strain and coping resources on burnout among Chinese medical professionals. A total of 2,721 medical professionals were selected using the stratified cluster sampling method. A Chinese version of the Maslach Burnout Inventory-General Survey was used to measure burnout, whereas the Occupation Stress Inventory-Revised Edition was used to evaluate work stressors, personal strain, and coping resources. The structural equation model (SEM) was established to test the effect of work stressors, personal strain, and coping resources on burnout. Among the predictive factors for burnout, work stressors and personal strain were the primary risk factors, whereas coping resources make up the important protective factor. The result from SEM indicated that work stressors had both direct and indirect effects on burnout, with the indirect effect mediated by both personal strain and coping resources. Coping resources only affected burnout indirectly, as mediated by personal strain, whereas personal strain affected burnout independently. The results suggest that work stressors, personal strain, and coping resources play important roles in burnout among medical professionals. To prevent burnout, such countermeasures as controlling the work stressors, reducing personal strain, and strengthening coping resources are recommended. PMID- 22673360 TI - Neural sensitivity to sex steroids predicts individual differences in aggression: implications for behavioural evolution. AB - Testosterone (T) regulates many traits related to fitness, including aggression. However, individual variation in aggressiveness does not always relate to circulating T, suggesting that behavioural variation may be more closely related to neural sensitivity to steroids, though this issue remains unresolved. To assess the relative importance of circulating T and neural steroid sensitivity in predicting behaviour, we measured aggressiveness during staged intrusions in free living male and female dark-eyed juncos (Junco hyemalis). We compared aggressiveness to plasma T levels and to the abundance of androgen receptor (AR), aromatase (AROM) and oestrogen receptor alpha (ORalpha) mRNA in behaviourally relevant brain areas (avian medial amygdala, hypothalamus and song control regions). We also asked whether patterns of covariation among behaviour and endocrine parameters differed in males and females, anticipating that circulating T may be a better predictor of behaviour in males than in females. We found that circulating T related to aggressiveness only in males, but that gene expression for ORalpha, AR and AROM covaried with individual differences in aggressiveness in both sexes. These findings are among the first to show that individual variation in neural gene expression for three major sex steroid-processing molecules predicts individual variation in aggressiveness in both sexes in nature. The results have broad implications for our understanding of the mechanisms by which aggressive behaviour may evolve. PMID- 22673362 TI - Predictors of sickness absence in patients with a new episode of low back pain in primary care. AB - This study examines predictors of sickness absence in patients presenting to a health practitioner with acute/ subacute low back pain (LBP). Aims of this study were to identify baseline-variables that detect patients with a new LBP episode at risk of sickness absence and to identify prognostic models for sickness absence at different time points after initial presentation. Prospective cohort study investigating 310 patients presenting to a health practitioner with a new episode of LBP at baseline, three-, six-, twelve-week and six-month follow-up, addressing work-related, psychological and biomedical factors. Multivariate logistic regression analysis was performed to identify baseline-predictors of sickness absence at different time points. Prognostic models comprised 'job control', 'depression' and 'functional limitation' as predictive baseline-factors of sickness absence at three and six-week follow-up with 'job control' being the best single predictor (OR 0.47; 95%CI 0.26-0.87). The six-week model explained 47% of variance of sickness absence at six-week follow-up (p<0.001). The prediction of sickness absence beyond six-weeks is limited, and health practitioners should re-assess patients at six weeks, especially if they have previously been identified as at risk of sickness absence. This would allow timely intervention with measures designed to reduce the likelihood of prolonged sickness absence. PMID- 22673363 TI - Calculating workplace WBGT from meteorological data: a tool for climate change assessment. AB - The WBGT heat stress index has been well tested under a variety of climatic conditions and quantitative links have been established between WBGT and the work rest cycles needed to prevent heat stress effects at the workplace. While there are more specific methods based on individual physiological measurements to determine heat strain in an individual worker, the WBGT index is used in international and national standards to specify workplace heat stress risks. In order to assess time trends of occupational heat exposure at population level, weather station records or climate modelling are the most widely available data sources. The prescribed method to measure WBGT requires special equipment which is not used at weather stations. We compared published methods to calculate outdoor and indoor WBGT from standard climate data, such as air temperature, dew point temperature, wind speed and solar radiation. Specific criteria for recommending a method were developed and original measurements were used to evaluate the different methods. We recommend the method of Liljegren et al. (2008) for calculating outdoor WBGT and the method by Bernard et al. (1999) for indoor WBGT when estimating climate change impacts on occupational heat stress at a population level. PMID- 22673364 TI - Do workaholism and work engagement predict employee well-being and performance in opposite directions? AB - This study investigated the distinctiveness between workaholism and work engagement by examining their longitudinal relationships (measurement interval=7 months) with well-being and performance in a sample of 1,967 Japanese employees from various occupations. Based on a previous cross-sectional study (Shimazu & Schaufeli, 2009), we expected that workaholism predicts future unwell-being (i.e., high ill-health and low life satisfaction) and poor job performance, whereas work engagement predicts future well-being (i.e., low ill-health and high life satisfaction) and superior job performance. T1-T2 changes in ill-health, life satisfaction and job performance were measured as residual scores that were then included in the structural equation model. Results showed that workaholism and work engagement were weakly and positively related to each other. In addition, workaholism was related to an increase in ill-health and to a decrease in life satisfaction. In contrast, work engagement was related to a decrease in ill-health and to increases in both life satisfaction and job performance. These findings suggest that workaholism and work engagement are two different kinds of concepts that are oppositely related to well-being and performance. PMID- 22673365 TI - Predictors of success on Wound Ostomy Continence Nursing certification board examinations: a regression study of academic factors. AB - PURPOSE: The aim of this study was to investigate the predictive validity of selected programmatic factors of a Wound Ostomy Continence Nursing Education Program (WOCNEP) on graduates' success when completing their certification examinations. SUBJECTS AND SETTING: First-time certification examination candidates over a 10-year period graduating from 1 WOCNEP located in the northeastern section of the United States comprised the sample. METHODS: Logistic regression analyses were used to determine the predictive value of academic factors (entry-level grade point average [GPA], test scores from the 2 WOCNEP courses, scores in a comprehensive final examination, and scores on the Wound, Ostomy and Continence Nursing Certification Board [WOCNCB] self-assessment examinations). Program format (on-site vs online study) was not analyzed due to the small online sample size. RESULTS: The predictive power of academic factors for WOCNCB certification success is similar to findings in published literature. Entry-level GPA, 4 course examination test scores, comprehensive final examination score, and 3 self-assessment examination (SAE) tests accounted for 56% of the variance in successful passing of the WOCNCB examinations (chi2 = 25.98, P < .01, R = 0.56). Entry-level GPA (R = 0.18, P < .01) and performance in course work (4 test scores) (R = 0.31, P < .01) were the strongest predictors. CONCLUSIONS: Study findings suggest that entry-level GPA and achievement in academic course work are most predictive of successful completion of WOCNCB certification examination. PMID- 22673366 TI - Pseudoaneurysm of the ascending aorta with perforation into the left atrium presenting as acute heart failure. PMID- 22673367 TI - Prognostic significance of long-period heart rate rhythms in chronic heart failure. AB - BACKGROUND: Abnormalities in autonomic control are a feature of neuroendocrine activation in HF and are responsible for dysregulation of biological rhythms. The purpose was to investigate the presence and the prognostic significance of long period heart rate (HR) rhythms in heart failure (HF) patients. METHODS AND RESULTS: In the study, 92 HF patients were enrolled (age 53 +/- 14 years and left ventricular ejection fraction [LVEF] 37 +/- 10%). A rhythmometric analysis was used to assess the HR rhythms in 7-days (7D) Holter recordings. Rhythms properties were quantified by mesor and amplitude, in beats/min and by acrophase, in hours. Cardiac death or HF decompensation were registered. All patients had 24 h rhythm, 61 patients (77%) had 8-h rhythm, and 66 patients (83%) had 7D rhythm. Twelve patients (15%) experienced events. Among rhythm parameters only 7D median amplitude was different between patients with or without events: 1.1 beats/min [0.5-1.5] vs. 2.0 beats/min [0.0-3.9], P=0.049 respectively. After multivariate adjustment, LVEF (per 1%, hazard ratio 0.92, 95% confidence interval (CI) 0.87 to 0.98, P=0.01), N-terminal portion of pro-natriuretic hormone type B (per 100 pg/ml, hazard ratio 1.036, 95% CI 1.005-1.069, P=0.022), and 7D amplitude of the HR <=1.71 beats/min (hazard ratio 5.4, 95% CI 1.2-34.4, P=0.047) were independent predictors of events. CONCLUSIONS: A 7D HR rhythm is present in most patients with HF, and has prognostic significance. PMID- 22673369 TI - High-purity enrichment of functional cardiovascular cells from human iPS cells. AB - AIMS: A variety of human inherited heart diseases affect the normal functions of cardiomyocytes (CMs), endothelial cells (ECs), or smooth muscle cells (SMCs). To study human heart disease and generate cardiac cells for basic and translational research, an efficient strategy is needed for production of cardiac lineages from human stem cells. In the present study, a highly reproducible method was developed that can simultaneously enrich a large number of CMs and cardiac SMCs and ECs from human induced pluripotent stem (iPS) cells with high purity. METHODS AND RESULTS: Human multipotent cardiovascular progenitor cells were generated from human iPS cells, followed by selective differentiation of the multipotent cardiovascular progenitor cells into CMs, ECs, and SMCs. With further fluorescence-activated cell sorting, each of the three cardiovascular cell types could be enriched with high purity (>90%). These enriched cardiovascular cells exhibited specific gene expression signatures and normal functions when assayed both in vitro and in vivo. Moreover, CMs purified from iPS cells derived from a patient with LEOPARD syndrome, a disease characterized by cardiac hypertrophy, showed the expected up-regulated expression of genes associated with cardiac hypertrophy. CONCLUSIONS: Overall, our technical advance provides the means for generating a renewable resource of pure human cardiovascular cells that can be used to dissect the mechanisms of human inherited heart disease and for the future development of drug and cell therapeutics for heart disease. PMID- 22673370 TI - Prolonged hypoxia augments L-citrulline transport by system A in the newborn piglet pulmonary circulation. AB - AIMS: Pulmonary arterial endothelial cells (PAECs) express the enzymes needed for generation of l-arginine from intracellular l-citrulline but do not express the enzymes needed for de novo l-citrulline synthesis. Hence, l-citrulline levels in PAECs are dependent on l-citrulline transport. Once generated, l-arginine can be converted to l-citrulline and nitric oxide (NO) by the enzyme NO synthase. We sought to determine whether hypoxia, a condition aetiologically linked to pulmonary hypertension, alters the transport of l-citrulline and the expression of the sodium-coupled neutral amino acid transporters (SNATs) in PAECs from newborn piglets. METHODS AND RESULTS: PAECs isolated from newborn piglets were cultured under normoxic and hypoxic conditions and used to measure SNAT1, 2, 3, and 5 protein expression and (14)C-l-citrulline uptake. SNAT1 protein expression was increased, while SNAT2, SNAT3, and SNAT5 expression was unaltered in hypoxic PAECs. (14)C-l-citrulline uptake was increased in hypoxic PAECs. Studies with inhibitors of System A (SNAT1/2) and System N (SNAT3/5) revealed that the increased (14)C-l-citrulline uptake was largely due to System A-mediated transport. Additional studies were performed to evaluate SNAT protein expression and l-citrulline levels in lungs of piglets with chronic hypoxia-induced pulmonary hypertension and comparable age controls. Lungs from piglets raised in chronic hypoxia exhibited greater SNAT1 expression and higher l-citrulline levels than lungs from controls. CONCLUSION: Increased SNAT1 expression and the concomitant enhanced ability to transport l-citrulline in PAECs could represent an important regulatory mechanism to counteract NO signalling impairments known to occur during the development of chronic hypoxia-induced pulmonary hypertension in newborns. PMID- 22673371 TI - Effects of age, ethnicity and health behaviours on the prevalence of adverse birth outcomes in Taiwan. AB - This study sampled 8432 singleton first live births from Taiwan's 2005 Birth Registration Database to determine if there were more pre-term or low birth weight deliveries among aboriginal women than there were among Han Chinese women, and if the 'weathering' hypothesis applied to aboriginal women in Taiwan. Although the aboriginal women were socially disadvantaged and engaged in more unhealthy behaviours, including smoking, drinking, chewing betel quid and exposure to second-hand smoke, the evidence did not support the hypothesis that these teenaged minority women would have better birth outcomes, as has been demonstrated among teenage African-American women in the United States. Behaviours and not ethnicity were risk factors for teenage aboriginal mothers, who started deleterious health behaviours earlier than did their older counterparts. Teenage mothers had more adverse outcomes regardless of ethnicity and aboriginal mothers had more risky behaviours in all age groups. The prevalence of detrimental health behaviour among teenage mothers in Taiwan is of concern, particularly for aboriginal teenage mothers. PMID- 22673372 TI - Commentary on "Altered and asymmetric default mode network activity in a "hypnotic virtuoso": an fMRI and EEG study". PMID- 22673373 TI - Bodily self and schizophrenia: the loss of implicit self-body knowledge. AB - Schizophrenia spectrum has been associated with a disruption of the basic sense of self, which pertains, among others, the representation of one's own body. We investigated the impact of either implicit or explicit access to the representation of one's own body-effectors on bodily self-awareness, in first episode schizophrenia (FES) patients and healthy controls (HCs). We contrasted their performance in an implicit self-recognition task (visual matching) and in an explicit self/other discrimination task. Both tasks employed participant's own and others' body-effectors. Concerning the implicit task, HCs were more accurate with their own than with others' body-effectors, whereas patients did not show such self-advantage. Regarding the explicit task, both groups did not exhibit a self-advantage, and patients showed a higher percentage of self-misattribution errors. Neither self/other nor implicit/explicit effects were found in both groups when processing inanimate-objects. We propose that FES patients suffer of a disturbed implicit sense of bodily self. PMID- 22673374 TI - Social awareness and early self-recognition. AB - Self-recognition by 86 children (14-52 months) was assessed using the mirror mark test in two different social contexts. In the classic mirror task condition, only the child was marked prior to mirror exposure (Classic condition). In the social norm condition, the child, experimenter, and accompanying parent were marked prior to the child's mirror exposure (Norm condition). Results indicate that in both conditions children pass the test in comparable proportion, with the same increase as a function of age. However, in the Norm condition, children displayed significantly more hesitation while removing the mark, often touching it without removing it or, if so, promptly putting the mark back onto their forehead. In the Classic condition, only one child showed such hesitation. These results suggest that from the outset, mirror self-recognition can refer to social awareness. This link is interpreted as the trademark of human self-consciousness, a deeply rooted "looking glass" self-awareness. PMID- 22673375 TI - Individualism and the field viewpoint: cultural influences on memory perspective. AB - Two perspectives from which memories can be retrieved have been distinguished: field resembles the view from the first-person vantage point of original experience, whereas observer resembles the view from the third-person vantage point of a spectator. There is evidence that the incidences of the two types of perspective differ between at least two different cultural groups. It is hypothesised here that this is a special case of a more general relation between memory perspective and cultural individualism, such that field and observer perspectives are more prevalent among people from, respectively, relatively individualist and relatively collectivist societies. Memory perspectives adopted by participants from a range of different countries were recorded, and were found to vary in the predicted manner. Regression analysis showed that the potential effects of three other cultural variables - uncertainty avoidance, masculinity and, to a lesser extent, power distance - were eclipsed by the influence of individualism, and the implications are discussed. PMID- 22673376 TI - [Hospital mortality is not a shortcut to the assessment of quality]. PMID- 22673377 TI - [Hospital standardised mortality ratios do not with certainty reflect the quality of patient care]. AB - Hospital standardised mortality ratios (HSMRs) are presumed to reflect an overall quality of patient care in hospitals. Figures for all Danish hospitals are being published quarterly on the Internet, and aggregated values are used to set goals for both regional and nationwide efforts to improve quality of care and patient safety. We have analysed the available data from 2007 through 2011 and cannot reconcile the quite substantial and often sudden changes in HSMRs with changes in quality of care, but believe that they are due to inherent noise in calculating HSMRs, e.g. owing to variable quality of the diagnostic coding. PMID- 22673378 TI - [A possible analgesic effect of nicotine on postoperative pain]. AB - Since postoperative pain often is undermanaged, and opioids, although being efficient analgesics, have undesirable side effects, attention has turned towards adjuvant therapies, among them nicotine. We present seven studies of which six show an effect of nicotine on postoperative pain when given in a low dose, with short time of exposure and to non-smokers. Other possible confounders are gender and type of anaesthesia. Nicotine seems to increase the occurrence of nausea and vomiting. More research is needed, and nicotine cannot currently be recommended as part of a multimodal pain management regime. PMID- 22673379 TI - [Metformin associated with lactic acidosis in treatment of type 2 diabetes]. AB - Metformin (MET) is the first-line agent in treatment of type 2 diabetes. However, MET has been associated with lactic acidosis (MALA), a potential but rare complication which has influenced treatment strategies in decades. Recently, guidelines have been changed in regards of age and heart failure and the contradiction of chronic renal impairment has been debated. This article identifies potential risk groups and situations that would benefit from a temporary interruption in the MET treatment. PMID- 22673380 TI - [Metformin-associated lactic acidosis can be treated with continuous renal replacement therapy]. AB - Metformin is widely used to treat diabetes. In rare cases, metformin may cause lactic acidosis, especially when administered during periods of dehydration. We present two cases of metformin-associated lactic acidosis (MALA). Both patients presented with metabolic acidosis, hypotension, renal failure and gastrointestinal symptoms. The use of continuous renal replacement therapy (CRRT) had a significant effect. Lactate and metformin can be removed effectively by haemofiltration. CRRT is widely available and a well-known treatment at intensive care units. MALA shows a mortality rate of about 30%. PMID- 22673381 TI - [Treatment of metformin-associated lactate acidosis by haemodialysis]. AB - Metformin-associated lactate acidosis is rare but serious and characterized by metabolic acidosis and elevated lactate. We describe a single-institution experience of four cases in one year. Despite pH levels of 6.85 to 7.12 and lactate levels of 11-28 mmol/l three of the patients survived. Two of the patients had normal kidney function previous to hospitalization. Treatment includes fluid replacement, IV sodium bicarbonate and haemodialysis. PMID- 22673382 TI - [Glucagon-like peptide 1 analogues in the treatment of type 2 diabetes mellitus]. AB - A Cochrane analysis concluded that glucagon-like peptide-1 (GLP-1) analogues were effective for the improvement of glycaemic control in patients with type 2 diabetes. What is the significance for the treatment of Danish patients with type 2 diabetes? In Denmark, two drugs exist, exenatid and liraglutid, and they both reduce HbA1c with approx. 1%. Compared with sulfonylurea and insulin, the advantage of GLP-1 analogues is not only that they rarely induce hypoglycaemia, but also that body weight is reduced. On the other hand, no long-term results exist with regard to impact on the cardiovascular system, and no complete overview of possible side effects has been presented either. PMID- 22673383 TI - [Recurrent erythema multiforme triggered by herpes simplex virus]. AB - We describe two cases of recurrent erythema multiforme, both associated to infection with herpes simplex virus. The importance of subclinical herpes is illustrated. Antiviral and additional treatment is described. PMID- 22673384 TI - [Cronkhite-Canada syndrome is a rare polyposis syndrome]. AB - Cronkhite-Canada syndrome (CCS) is rare and associated with diarrhoea, gastrointestinal polyps, malnutrition, weight loss, alopecia, skin- and nail changes. The patient was hospitalized with dehydration, diarrhoea and weight loss. Objectively emaciated, skin changes, poor nail status and alopecia. Biochemistry compatible with malnutrition. Gastroscopy showed polyps. Treatment of symptomatic replacement therapy and prednisolone resulted in remission. It is a diagnosis with a 55% 5-year mortality. Early treatment leads to better prognosis. PMID- 22673385 TI - [Bannayan-Riley-Ruvalcaba syndrome and juvenile polyposis in a two-year-old girl]. AB - Bannayan-Riley-Ruvalcaba syndrome is a rare disease, which is characterized by macrocephaly, benign hamartomas, lipomas, haemangiomas, pigmented maculae, developmental delay and mental retardation. This case report describes how the combination of macrocephaly, hypertelorism, high palate and intestinal polyposis led to the diagnosis of this syndrome in a two year and seven month-old girl. The diagnosis was confirmed by molecular genetic analysis showing deletion of the entire PTEN gene and the majority of the neighbouring gene BMPR1A, which predisposes to juvenile polyposis. PMID- 22673386 TI - [Perianal Buschke-Lowenstein tumour]. AB - The Buschke-Lowenstein tumour is an extremely rare, slow-growing cauliflower-like mass, also known as giant condyloma acuminantum or verrucous carcinoma. It is located in the anogenital region and is characterized by its large size, locally destructive behaviour and a high recurrence rate. It has not the potentiel to metastasize but malignant transformation can occur. We report a case of a 49-year old male patient with a 17 * 10 cm large perianal Buschke-Lowenstein tumour where histologic findings showed the presence of verrucous carcinoma. PMID- 22673387 TI - Antineutrophil cytoplasm autoantibodies: usefulness in rheumatology. AB - The primary vasculitidies are complex diseases with varied clinical manifestations, which may be common to those present in multiple diseases. The antineutrophil cytoplasm autoantibodies (ANCA) led to a revolution in the diagnosis and research of these diseases, being the first and so far, the only biomarkers for three of these diseases, which affect small caliber vessels. From their description, much progress has been made, but there are still gray or misunderstood areas regarding their best use in the clinic. This can lead to errors as making a positive test synonym for vasculitis, or to overestimation of its importance. This review will address aspects such as nomenclature, employment in the diagnosis and monitoring of vasculitis, their presence in other diseases, their methods of detection, and finally, some comments on other potential biomarkers in vasculitis. PMID- 22673388 TI - Patient survival and safety with biologic therapy. Results of the Mexican National Registry Biobadamex 1.0. AB - This work reports patient treatment survival and adverse events related to Biologic Therapy (BT), identified by a multicenter ambispective registry of 2047 rheumatic patients undergoing BT and including a control group of Rheumatoid Arthritis (RA) patients not using BT. The most common diagnoses were: RA 79.09%, Ankylosing Spondilytis 7.96%, Psoriatic Arthritis 4.40%, Systemic Lupus Erythematosus 3.37%, Juvenile Idiopathic Arthritis 1.17%. A secondary analysis included 1514 cases from the total sample and was performed calculating an incidence rate of any adverse events of 178 * 1000/BT patients per year vs 1009 * 1000/control group patients per year with a 1.6 RR (95% CI 1.4-1.9). For serious adverse events the RR was: 15.4 (95% CI 3.7-63.0, P<.0001). Global BT survival was 80% at 12 months, 61% at 24 months, 52% at 36 months and 45% at 48 months and SMR: 0.23 (95% CI 0.0-49.0) for BT vs 0.00 (95% CI 0.0-0.2) for the control group. In conclusion, BT was associated to a higher infection risk and adverse events, compared to other patients. Mortality using BT was not higher than expected for general population with same gender and age. PMID- 22673389 TI - YAlO3:Cr3+ nanophosphor: synthesis, photoluminescence, EPR, dosimetric studies. AB - YAlO(3):Cr(3+) (0.1 mol%) nanophosphor has been synthesized by low temperature solution combustion method. The X-ray diffraction studies reveal an orthorhombic structure. Transmission electron microscopy reveals that the particles are spherical in shape with nano-size ~40-65 nm. Electron paramagnetic resonance (EPR) spectrum shows a resonance signal with effective g value at g=1.978 which can be attributed to the exchange coupled Cr(3+) ion pairs in weakly distorted sites. The photoluminescence spectrum shows an intense doublet at 677 nm and 694 nm (R lines) assigned to spin-forbidden (2)E(g)->(4)A(2)(g) transition of Cr(3+) ions. EPR and PL studies reveal that the Cr(3+) ions occupy Al(3+) sites in YAlO(3). The interesting feature reported in this work concerns the linearity with gamma dose in the wide range (0.1-6 kGy). Prominent TL glow peaks at 226 degrees C and 346 degrees C were observed for both gamma and UV-rays respectively. It is observed that the peaks at 226 degrees C and 346 degrees C eventually show a linear response up to 5 kGy which makes them a candidate for high dose dosimetry of ionizing radiation. The kinetic parameters namely activation energy (E), order of kinetics (b), frequency factor (s) of undoped and Cr doped samples were determined using Chens glow peak shape method and the results are discussed in detail. PMID- 22673391 TI - Clinical advances of interest in the diagnosis and treatment of patients with antiphospholipid syndrome. AB - In this paper we review recent studies and consensus documents that we consider relevant to the diagnosis and treatment of patients with antiphospholipid syndrome (APS). The diagnosis of APS is based on the Sydney classification criteria (2006), in which positive laboratory tests (anticardiolipin antibodies, anti-beta2-glycoprotein I antibodies or lupus anticoagulant) are mandatory. However, it is not uncommon to see patients with clinical features highly suggestive of the syndrome in whom these antibodies are persistently negative. Therefore, we summarize the principal clinical and serological findings in a subgroup of patients with seronegative APS in the first series published up to date. In addition, a recent study draws attention to the safety and efficacy of the long-term use of low-molecular-weight heparins in patients with APS not susceptible to warfarin treatment. There is also a subgroup of women with APS and recurrent fetal loss with no response to the standard antithrombotic therapy; in this group the materno-fetal prognosis could be improved by the addition of low dose prednisolone during the first trimester of pregnancy. Finally, we list the principal recommendations regarding thromboprophylaxis in APS drawn from the expert consensus document elaborated at the meeting held in Galvestone (2010). PMID- 22673390 TI - Anti-angiogenic therapy increases intratumoral adenovirus distribution by inducing collagen degradation. AB - Conditionally replicating adenoviruses (CRAd) are a promising class of gene therapy agents that can overcome already known glioblastoma (GBM) resistance mechanisms but have limited distribution upon direct intratumoral (i.t.) injection. Collagen bundles in the extracellular matrix (ECM) have an important role in inhibiting virus distribution. In fact, ECM pre-treatment with collagenases improves virus distributions to tumor cells. Matrix metalloproteinases (MMPs) are an endogenous class of collagenases secreted by tumor cells whose function can be altered by different drugs including anti angiogenic agents, such as bevacizumab. In this study we hypothesized that upregulation of MMP activity during anti-angiogenic therapy can improve CRAd-S pk7 distribution in GBM. We find that MMP-2 activity in human U251 GBM xenografts increases (*P=0.03) and collagen IV content decreases (*P=0.01) during vascular endothelial growth factor (VEGF-A) antibody neutralization. After proving that collagen IV inhibits CRAd-S-pk7 distribution in U251 xenografts (Spearman rho= 0.38; **P=0.003), we show that VEGF-blocking antibody treatment followed by CRAd S-pk7 i.t. injection reduces U251 tumor growth more than each individual agent alone (***P<0.0001). Our data propose a novel approach to improve virus distribution in tumors by relying on the early effects of anti-angiogenic therapy. PMID- 22673392 TI - [Cutaneous larva migrans]. PMID- 22673393 TI - Application of antioxidants and centrifugation for cryopreservation of boar spermatozoa. AB - Although cryopreserved boar semen has been available since 1975, a major breakthrough in commercial application has not yet occurred due to the high susceptibility of boar spermatozoa to damage during cryopreservation and the complicated process required for deep freezing. In recent years, the application of antioxidants during the cryopreservation of boar semen has been the subject of considerable research aimed at improving the quality of post-thaw semen. Centrifugation is necessary before using cryopreservation protocols for freezing boar spermatozoa. Studies of the effect of different centrifugation regimens on boar sperm recovery, yield and cryosurvival have made significant contributions. Therefore this review elucidates results of recent applications of various antioxidants and centrifugation regimens used in efforts to improve cryopreservation of boar spermatozoa. This review is intended to enhance understanding of the roles of these antioxidants and centrifugation regimens with respect to mechanisms that increase resistance to cryodamage of boar spermatozoa. In addition, the discussion addresses the need for developing an objective evaluation of effectiveness and estimating the prospect of application of new techniques for the cryopreservation of boar semen and its use in artificial insemination. PMID- 22673394 TI - Specificity of the extender used for freezing ram sperm depends of the spermatozoa source (ejaculate, electroejaculate or epididymis). AB - The objective of this study was to identify possible specificity in the extender formulation for the cryopreservation of ram spermatozoa recovered from three origins (ejaculate, electroejaculate or epididymis), by evaluating post-thawing sperm quality and fertility. Ejaculated, electroejaculated or epididymal spermatozoa samples obtained from identical rams (8) were cryopreserved in four different extenders (TES-Tris-fructose with one of two egg yolk concentrations: 10% Y10 and 20% Y20, and with one of two glycerol rates: 4% G4 and 8% G8). Samples were analyzed before and after cryopreservation by CASA (motility) and flow cytometry (viability with SYBR-14/PI and acrosomal status with PNA/PI). Spermatozoa obtained by electroejaculation were of poorer quality after freezing/thawing, demonstrating that protocols for these samples need to be optimized. Egg yolk at 20% was more appropriate for freezing sperm from any of the sources. In general, 4% glycerol improved the quality of post-thawing samples recovered from ejaculate and electroejaculate, while 8% glycerol was more appropriate for samples recovered from the epididymis. Based on these results, an analysis of fertility was conducted. Fertility rates were similar between ewe groups inseminated with post-thawed sperm obtained from two sources: ejaculate (cryopreserved in Y20+G4), and cauda epididymis (Y20+G8), and this rate was less in the electroejaculated sample (Y20+G4). PMID- 22673396 TI - Occurrence of cerebrocortical necrosis in a goat in Okinawa prefecture, Japan. AB - A 6-month-old male Nubian goat suddenly showed dullness, tachypnea, recumbency and opisthotonus in August 2011 in Okinawa, Japan. The goat was consequently necropsied: gross lesions in the brain included slightly swollen foci of yellowish discoloration on the cerebral hemisphere. Histopathologically, necrosis of the cortex with ischemic changes of neuronal cells was present, and swelling of the vascular endothelium, thickening of the basement membrane and diffuse infiltration of macrophages were observed in the cerebral lesion. Autofluorescence of the cerebral cortex was confirmed by an ultraviolet light test. The thiamine levels of the blood serum and tissue samples (brain, liver and heart) of the goat were low compared with goats from the same herd. The goat was diagnosed with cerebrocortical necrosis (CCN). This is the first case report of caprine CCN in Japan. PMID- 22673395 TI - Modeling stochasticity and variability in gene regulatory networks. AB - Modeling stochasticity in gene regulatory networks is an important and complex problem in molecular systems biology. To elucidate intrinsic noise, several modeling strategies such as the Gillespie algorithm have been used successfully. This article contributes an approach as an alternative to these classical settings. Within the discrete paradigm, where genes, proteins, and other molecular components of gene regulatory networks are modeled as discrete variables and are assigned as logical rules describing their regulation through interactions with other components. Stochasticity is modeled at the biological function level under the assumption that even if the expression levels of the input nodes of an update rule guarantee activation or degradation there is a probability that the process will not occur due to stochastic effects. This approach allows a finer analysis of discrete models and provides a natural setup for cell population simulations to study cell-to-cell variability. We applied our methods to two of the most studied regulatory networks, the outcome of lambda phage infection of bacteria and the p53-mdm2 complex. PMID- 22673397 TI - Identification of novel immunogenic proteins in Mycoplasma capricolum subsp. Capripneumoniae strain M1601. AB - The purpose of this study was to obtain immunogenic proteins and potential proteins of interest that were isolated from Mycoplasma capricolum subsp. capripneumoniae (Mccp) by MALDI-TOF mass spectrometry. One-dimensional SDS-PAGE and two-dimensional gel electrophoresis of whole cell preparation were conducted, and membrane proteome maps were prepared by immunoblotting. One-dimensional SDS PAGE identified three immunogenic proteins with molecular masses in the range 29 97.2 kDa, two of which were in the membrane protein fraction. After two dimensional gel electrophoresis, 20 highly immunogenic proteins were identified in the whole cell protein preparation while 9 immunogenic proteins were identified in the membrane protein fraction. This indicated that membrane proteins were the principle immunogenic proteins in Mccp. These proteins may have potential for the development of improved diagnostic tests and possible vaccines. PMID- 22673398 TI - Bio-augmentation to rapid realize partial nitrification of real sewage. AB - The feasibility of bio-augmentation processes in promoting start-up of partial nitrification of sewage was investigated in this study. Initially, partial nitrification was well-established in an anoxic/oxic reactor treating high strength ammonia wastewater. Then the influent was replaced by real sewage instantly or gradually. In both cases, nitrite pathway could be maintained for 5 7d. However, it was eventually destroyed due to the inevitable over-aeration. In another strategy, sewage was treated in the adsorption/biodegradation reactor. The nitrite pathway was obviously promoted by addition of the previous activated sludge from high ammonia wastewater treatment. Nitrite accumulation efficiency of sewage was quickly increased from 26% to 86% and maintained at a high level for 2 months. Moreover, the effluent has a favorable ratio of NH(4)(+)/NO(2)(-) for feeding anammox process. The experimental results indicated that appropriate bio augmentation strategies could significantly improve the build-up partial nitrification of sewage in the pretreatment of anammox. PMID- 22673399 TI - Treatment of tannery wastewater in a pilot-scale hybrid constructed wetland system in Bangladesh. AB - This paper reports the pollutant removal performances of a hybrid wetland system in Bangladesh for the treatment of a tannery wastewater. The system consisted of three treatment stages: a subsurface vertical flow (VF) wetland, followed by a horizontal flow (HF) and a VF wetland. The wetlands were planted with common reed (Phragmites australis), but employed different media, including organic coco peat, cupola slag and pea gravel. In the first stage, experimental results demonstrated significant removal of ammonia (52%), nitrate (54%), BOD (78%), and COD (56%) under high organics loading rate (690 g COD m(-2)d(-1)); simultaneous nitrification, denitrification, and organics degradation were attributed to the unique characteristics of the coco-peat media, which allowed greater atmospheric oxygen transfer for nitrification and organic degradation, and supply of organic carbon for denitrification. The second stage HF wetland produced an average PO(4) removal of 61%, primarily due to adsorption by the iron-rich cupola slag media. In the third treatment stage, which was filled with gravel media, further BOD removal (78%) from the tannery wastewater depleted organic carbon, causing the accumulation of NO(3) in the wastewater. Overall, the average percentage removals of NH(3)-N, NO(3)-N, BOD, COD, and PO(4) were 86%, 50%, 98%, 98% and 87%, respectively, across the whole hybrid system. The results provided a strong evidence to support widespread research and application of the constructed wetland as a low-cost, energy-efficient, wastewater treatment technology in Bangladesh. PMID- 22673400 TI - Seasonal variations of CH4 and N2O emissions in response to water management of paddy fields located in Southeast China. AB - Water management is one of the most important practices that affect methane (CH(4)) and nitrous oxide (N(2)O) emissions from paddy fields. A field experiment was designed to study the effects of controlled irrigation (CI) on CH(4) and N(2)O emissions from paddy fields, with traditional irrigation (TI) as the control. The effects of CI on CH(4) and N(2)O emissions from paddy fields were very clear. The peaks of CH(4) emissions from the CI paddies were observed 1-2d after the water layer disappeared. Afterward, the emissions reduced rapidly and remained low until the soil was re-flooded. A slight increase of CH(4) emission was observed in a short period after re-flooding. N(2)O emissions peaks from CI paddies were all observed 8-10d after the fertilization at the WFPS ranging from 78.1% to 85.3%. Soil drying caused substantial N(2)O emissions, whereas no substantial N(2)O emissions were observed when the soil was re-wetted after the dry phase. Compared with TI, the cumulative CH(4) emissions from the CI fields were reduced by 81.8% on the average, whereas the cumulative N(2)O emissions were increased by 135.4% on the average. The integrative global warming potential of CH(4) and N(2)O on a 100-year horizon decreased by 27.3% in the CI paddy fields, whereas no significant difference in the rice yield was observed between the CI and TI fields. These results suggest that CI can effectively mitigate the integrative greenhouse effect caused by CH(4) and N(2)O emissions from paddy fields while ensuring the rice yield. PMID- 22673401 TI - Pesticide residue dynamics in passion fruits: comparing field trial and modelling results. AB - We evaluated the exposure to pesticides from the consumption of passion fruits and subsequent human health risks by combining several methods: (i) experimental field studies including the determination of pesticide residues in/on passion fruits, (ii) dynamic plant uptake modelling, and (iii) human health risk assessment concepts. Eight commonly used pesticides were applied onto passion fruits cultivated in Colombia. Pesticide concentrations were measured periodically (between application and harvest) in whole fruits and fruit pulp. Measured concentrations were compared with predicted residues calculated with a dynamic and crop-specific pesticide uptake model, namely dynamiCROP. The model accounts for the time between pesticide application and harvest, the time between harvest and consumption, the amount of spray deposition on plant surfaces, uptake processes, dilution due to crop growth, degradation in plant components, and reduction due to food processing (peeling). Measured and modelled residues correspond well (r(2)=0.88-0.99), with all predictions falling within the 90% confidence interval of the measured values. A mean error of 43% over all studied pesticides was observed between model estimates and measurements. The fraction of pesticide applied during cultivation that is eventually ingested by humans is on average 10(-4)-10(-6), depending on the time period between application and ingestion and the processing step considered. Model calculations and intake fractions via fruit consumption based on experimental data corresponded well for all pesticides with a deviation of less than a factor of 2. Pesticide residues in fruits measured at recommended harvest dates were all below European Maximum Residue Limits (MRLs) and therefore do not indicate any violation of international regulatory thresholds. PMID- 22673402 TI - Fracture of left ventricular pacing lead stabilized using the retained guidewire technique. PMID- 22673403 TI - Putative link between Staphylococcus aureus bacteriophage serotype and community association. AB - Methicillin-resistant Staphylococcus aureus (MRSA) from humans can be broadly separated into 3 groups: healthcare-associated (HA), community-associated (CA), and livestock-associated (LA) MRSA. Initially based on epidemiological features, division into these classes is becoming increasingly problematic. The sequencing of S. aureus genomes has highlighted variations in their accessory components, which likely account for differences in pathogenicity and epidemicity. In particular, temperate bacteriophages have been regarded as key players in bacterial pathogenesis. Bacteriophage-associated Panton-Valentine leukocidin genes (luk-PV) are regarded as epidemiological markers of the CA-MRSA due to their high prevalence in CA strains. This paper describes the development and application of a partial composite S. aureus virulence-associated gene microarray. Epidemic, pandemic, and sporadic lineages of UK HA and CA S. aureus were compared. Phage structural genes linked with CA isolates were identified and in silico analysis revealed these to be correlated with phage serogroup. CA strains predominantly carried a PVL-associated phage either of the A or Fb serogroup, whilst HA strains predominantly carried serogroup Fa or B phages. We speculate that carriage of a serogroup A/Fb PVL-associated phage rather than the luk-PV genes specifically is correlated with CA status. PMID- 22673404 TI - Estrogen mediated effects in the Sydney rock oyster, Saccostrea glomerata, following field exposures to sewage effluent containing estrogenic compounds and activity. AB - The Sydney rock oyster, Saccostrea glomerata, has been demonstrated as a useful biomonitor of estrogenic compounds following laboratory exposures, yet its utility in the assessment of estrogenic exposure and effects under field conditions requires investigation. To achieve this aim, S. glomerata were deployed in Newcastle, Australia in the effluent receiving marine waters of Burwood Beach WWTP (Burwood Beach "near", <50 m from outfall and Burwood Beach "far", 100-150 m from outfall) and reference locations (Redhead, Fingal Island 1 and Fingal Island 2) at depths of 4, 8 and 12 m for six weeks. Effluent receiving waters of Burwood Beach WWTP were found to be a suitable impact location, demonstrated via measurement of estrogenic compounds and activity throughout the deployment. Estrogenic compounds were detected (average of combined solids and liquid fractions) at average concentrations of: 1.42 ng/L for estrone, 0.69 ng/L for 17beta estradiol, 3.83 ng/L for estriol (E3), 0.56 ng/L for 17alpha ethynylestradiol, 64.2 ng/L for bisphenol A, 7.51 ng/L for 4-nonylphenol and 5.93 ng/L for 4-tert-octylphenol. Total estrogenic activity was estimated at 4.48 ng/L EEQ via the Yeast Estrogen Screen (YES((r))) assay (average of combined solid and liquid fractions). Female vitellogenin gene expression was highest at Burwood Beach locations, yet no significant differences were detected among locations for either sex. Vitellogenin protein was significantly higher (p<0.05) in S. glomerata at Burwood Beach Near compared to reference locations for the 4 and 12 m depths. Increased proportions of females were found at Burwood Beach Near, at 4m depth (p<0.05). Both Burwood Beach locations had higher proportions of mature female gonadal development stages compared to reference locations (p<0.05). Oocyte area was highest at both Burwood Beach locations, but no significant differences were detected among locations. Findings provided further evidence that female S. glomerata may be a suitable candidate species for assessment of effects of estrogenic compounds in Australian waters. PMID- 22673405 TI - Effects of sublethal, environmentally relevant concentrations of hexavalent chromium in the gills of Mytilus galloprovincialis. AB - Hexavalent chromium Cr(VI) is an important contaminant released from both domestic and industrial effluents, and represents the predominant chemical form of the metal in aquatic ecosystems. In the marine bivalve Mytilus galloprovincialis exposure to non-toxic, environmentally relevant concentrations of Cr(VI) was shown to modulate functional parameters and gene expression in both the digestive gland and hemocytes. In this work, the effects of exposure to Cr(VI) (0.1-1-10 MUg L(-1) animal(-1) for 96 h) in mussel gills were investigated. Gill morphology and immunolocalization of GSH-transferase (GST), of components involved in cholinergic (AChE and ChAT), adrenergic (TH) and serotoninergic (5-HT(3) receptor) systems, regulating gill motility, were evaluated. Total glutathione content, activities of GSH-related enzymes (glutathione reductase - GSR, GST), of catalase, and of key glycolytic enzymes (phosphofructokinase - PFK and pyruvate kinase - PK) were determined. Moreover, mRNA expression of selected Mytilus genes (GST-pi, metallothionein isoforms MT10 and MT20, HSP70 and 5-HT receptor) was assessed by RT-q-PCR. Cr(VI) exposure induced progressive changes in gill morphology and in immunoreactivity to components involved in neurotransmission that were particularly evident at the highest concentration tested, and associated with large metal accumulation. Cr(VI) increased the activities of GST and GSR, and total glutathione content to a different extent at different metal concentrations, this suggesting Cr(VI) detoxication/reduction at the site of metal entry. Cr(VI) exposure also increased the activity of glycolytic enzymes, indicating modulation of carbohydrate metabolism. Significant changes in transcription of different genes were observed. In particular, the mRNA level for the 5-HTR was increased, whereas both decreases and increases were observed for GST-pi, MT10, MT20 and HSP70 mRNAs, showing sex- and concentration-related differences. The results demonstrate that Cr(VI) significantly affected functional and molecular parameters in mussel gills, and indicate that this tissue represents the major target of exposure to environmentally relevant concentrations of the metal. PMID- 22673406 TI - Standardized centile curves and reference intervals of serum insulin-like growth factor-I (IGF-I) levels in a normal Japanese population using the LMS method. AB - Measurements of insulin-like growth factor-I (IGF-I) are useful not only for diagnosis and management of patients with growth hormone (GH)-related disorders but also for assessing nutritional status. We reported population-based references of serum IGF-I in 1996. However, they did not properly reflect data in the transition period from puberty to maturity. The aim of the present study was to re-establish a set of normative data for IGF-I for the Japanese population. The study included 1,685 healthy Japanese subjects (845 males, 840 females) from 0 to 83 years old. Subjects suffering from diseases that could affect IGF-I levels were excluded. Obese or extremely thin adult subjects were also excluded. IGF-I concentrations were determined by commercially available immunoradiometric assays. The reference intervals were calculated using the LMS method. Median IGF-I levels reached 310 ng/mL in males at the age of 14 years and 349 ng/mL in females at the age of 13 years, falling to 124 ng/mL and 103 ng/mL, respectively, by the age of 70 years. The mean pretreatment IGF-1 SD scores in patients with severe GH deficiency (GHD) obtained from the database of the Foundation for Growth Science and from clinical studies for adult GHD were 2.1+/-1.6 and -4.9+/-2.5, respectively. The present study established age- and gender-specific normative IGF-I data for the Japanese population and showed the utility of these references for screening patients with severe GHD. PMID- 22673407 TI - Linear ubiquitination: a novel NF-kappaB regulatory mechanism for inflammatory and immune responses by the LUBAC ubiquitin ligase complex. AB - The NF-kappaB pathway is a central signaling pathway for inflammatory and immune responses, and aberrant NF-kappaB signaling is implicated multiple disorders, such as cancer and autoimmune, chronic inflammatory and metabolic diseases. NF kappaB is regulated by various post-translational modifications, including phosphorylation and multiple ubiquitinations. We determined that LUBAC (linear ubiquitin chain assembly complex), composed of SHARPIN, HOIL-IL and HOIP, generates a novel type of Met1-linked linear polyubiquitin chain and specifically regulates the canonical NF-kappaB pathway via the linear ubiquitination of NEMO and RIP1. In the absence of LUBAC components, NF-kappaB signaling was attenuated and induced apoptosis and inflammation. Many studies on the pathophysiological functions of LUBAC, such as in B cell development, innate immune response, carcinogenesis, and osteogenesis, have been performed recently. This review summarizes these new findings on LUBAC- and linear ubiquitination-mediated NF kappaB regulation and their implications in disorders. PMID- 22673408 TI - Association of GLUT4 gene variants with HbA1c level in Japanese men. AB - GLUT4 is a major mediator of glucose removal from the circulation and a key regulator of whole-body glucose homeostasis. Recent studies in south Indian populations revealed that haplotypes of the GLUT4 gene associated with type 2 diabetes. A total of 734 middle aged apparently healthy Japanese men were recruited from two separate occupational cohorts from Kanagawa and Kyoto. Participants were genotyped for GLUT4 variants, rs5418 (A/G) and rs2654185 (C/A), and association with HbA1c level was analyzed. The HbA1c value was determined by JDS method which is 0.4% lower than NGSP value. The G allele carrier of rs5418 and A allele carrier of rs2654185 associated with significantly higher HbA1c level (AG + GG vs. AA carriers; 5.2 +/- 0.8 vs. 4.9 +/- 0.4, P < 0.002, and AA + AC vs. CC; 5.2 +/- 0.9, vs. 4.9 +/- 0.4, P < 0.002, respectively). G allele, AG + GG genotype of rs5418 and A allele, AA + AC genotype of rs2654185 showed a significant association with higher HbA1c (beta = 0.215, P = 0.026; beta = 0.215, P = 0.026; beta = 0.190, P = 0.042; beta = 0.190, P = 0.042, respectively). These two SNPs are in high linkage disequilibrium (LD) of r(2) = 0.67. In haplotype analysis, four haplotypes were estimated. HbA1c is significantly higher in the most frequent GA haplotype compared with the second frequent AC haplotype (5.2% vs. 5.1%, P = 0.004). Genetic variations, rs5418 and rs2654185 in GLUT4 gene are associated with HbA1c level in Japanese men. PMID- 22673409 TI - Differences of the association of anti-Mullerian hormone with clinical or biochemical characteristics between women with and without polycystic ovary syndrome. AB - The aim of the present study was to compare the associations of anti-Mullerian hormone (AMH) with clinical or biochemical characteristics between women with and without polycystic ovary syndrome (PCOS). We also explored the optimal cutoff point of AMH to diagnose PCOS. A cross-sectional study was performed in 87 women diagnosed with PCOS and 53 healthy control subjects. Body mass index (BMI), indices of insulin resistance, metabolic syndrome-related variables, reproductive hormones and serum AMH were measured in all subjects. We conducted receiver operating characteristic (ROC) curve analysis to determine the cutoff of AMH for diagnosis of PCOS. Serum AMH levels were significantly (p <0.001) higher in women with PCOS after adjustment for age and BMI. AMH levels were not significantly related with obesity, indices of insulin resistance, and metabolic syndrome-related variables in both PCOS and control groups. In the control group, AMH levels showed positive correlations with total testosterone (p <0.001), free testosterone (p=0.024), and adiponectin (p=0.002), and showed negative correlations with age (p=0.010) and estradiol (E2) (p=0.012). However, only total (p=0.044) and free testosterone (p=0.012) levels showed significant positive correlations with serum AMH level in PCOS group. ROC curve analysis showed a cutoff point for AMH of 7.82 ng/mL (sensitivity 75.9%, specificity 86.8%) for diagnosis of PCOS. Differences of the association of AMH with clinical or biochemical characteristics between women with PCOS and control groups were observed. This might contribute to the pathogenesis of PCOS, although further investigation is necessary to elucidate the detailed mechanism. PMID- 22673410 TI - Specific glycan elements determine differential binding of individual egg glycoproteins of the human parasite Schistosoma mansoni by host C-type lectin receptors. AB - During infection with the blood fluke Schistosoma mansoni, glycan motifs present on glycoproteins of the parasite's eggs mediate immunomodulatory effects on the host. The recognition of these glycan motifs is primarily mediated by C-type lectin receptors on dendritic cells and other cells of the immune system. However, it is not yet known which individual glycoproteins interact with the different C-type lectin receptors, and which structural components are involved. Here we investigated the structural basis of the binding of two abundant egg antigens, kappa-5 and IPSE/a1, by the C-type lectin receptor dendritic cell specific ICAM3-grabbing non-integrin, macrophage galactose-type lectin and mannose receptor. In the natural soluble form, the secretory egg glycoprotein IPSE/a1 interacts with dendritic cells mainly via mannose receptors. Surprisingly, in plate-based assays mannose receptors preferentially bound to mannose conjugates, while in cell-based assays, IPSE/a1 is bound via the fucosylated Galb1-4(Fuca1-3)GlcNAc (LeX) motif on diantennary N-glycans. Kappa-5, in contrast, is bound by dendritic cells viaall three C-type lectin receptors studied and for a minor part also via other, non-C-type lectin receptors.Kappa-5 interacts with macrophage galactose-type lectins via the GalNAcb1-4GlcNAc antenna present on its triantennary N-glycans, as well as the GalNAcb1-4(Fuca1-3) GlcNAc antennae present on a minor N-glycan subset. Dendritic cell-specific ICAM3 grabbing non-integrin binding of kappa-5 was mediated via the GalNAcb1-4(Fuca1 3)GlcNAc antennae, whereas binding of mannose receptors may involve either GalNAcb1-4(Fuca1-3)GlcNAc antennae or the fucosylated and xylosylated chitobiose core. This study provides a molecular and structural basis for future studies of the interaction between C-type lectin receptors and other soluble egg antigen glycoproteins and their effects on the host immune response. PMID- 22673411 TI - Variables separation of the spectral BRDF for better understanding color variation in special effect pigment coatings. AB - A type of representation of the spectral bidirectional reflectance distribution function (BRDF) is proposed that distinctly separates the spectral variable (wavelength) from the geometrical variables (spherical coordinates of the irradiation and viewing directions). Principal components analysis (PCA) is used in order to decompose the spectral BRDF in decorrelated spectral components, and the weight that they have at every geometrical configuration of irradiation/viewing is established. This method was applied to the spectral BRDF measurement of a special effect pigment sample, and four principal components with relevant variance were identified. These four components are enough to reproduce the great diversity of spectral reflectances observed at different geometrical configurations. Since this representation is able to separate spectral and geometrical variables, it facilitates the interpretation of the color variation of special effect pigments coatings versus the geometrical configuration of irradiation/viewing. PMID- 22673412 TI - Spatially induced spatiotemporally nonspreading Airy-Bessel wave packets. AB - By studying the effect of spatially induced group velocity dispersion (SIGVD) during the propagation of ultrashort pulsed Bessel beams in free space, we numerically prove that third-order SIGVD can temporally cause Gaussian distribution of pulsed Bessel beams to gradually evolve as unsymmetrical trailing oscillatory structures. The pulse shape is confirmed to be temporal Airy distributions on the basis of the cross-correlation function. Therefore, it is demonstrated that the scheme of generating spatiotemporally nonspreading Airy Bessel wave packets in free space is possible by using a precompensating second order SIGVD. The results of numerical simulation show that the quasi-Airy pulses induced by third-order SIGVD are temporally nonspreading during propagation in dispersive media. The reasons for nonspreading of such Airy distribution pulses are phenomenologically analyzed by a time-frequency Wigner distribution function of the pulse. PMID- 22673413 TI - Photon-counting three-dimensional integral imaging with compression of elemental images. AB - In this paper, we present lossless compression of elemental images in photon counting integral imaging. In order to verify the performance of the compression method applied to low light level three-dimensional (3D) integral imaging, we compute the correlation coefficient and peak to mean square error (PSNR) as metrics for 3D scene reconstruction integrity. We show quantitatively via experiments that a considerable compression of the elemental images in photon counting integral imaging may be achievable without significant loss in the performance in terms of correlation and PSNR metrics. To the best of our knowledge, this is the first report on applying lossless compression algorithms in photon-counting 3D computational integral imaging. PMID- 22673414 TI - Reflection and refraction of an Airy beam at a dielectric interface. AB - Reflection and refraction of a finite-power Airy beam at the interface between two dielectric media are investigated analytically and numerically. The formulation takes into account the paraxial nature of the optical beams to derive convenient field evolution equations in coordinate frames moving along Snell's refraction and reflection axes. Through numerical simulations, the self accelerating dynamics of the Airy-like refracted and reflected beams are observed. Of special interest are the cases of critical incidence at Brewster and total-internal-reflection (TIR) angles. In the former case, we find that the reflected beam achieves self-healing, despite the severe suppression of a part of its spectrum, while, in the latter case, the beam remains nearly unaffected except for the Goos-Hanchen shift. The self-accelerating quality persists even if the beam is trapped by multiple TIRs inside a dielectric film. The grazing incidence of an Airy beam at the interface between two media with close refractive indices is also investigated, revealing that the interface can act as a filter depending on the beam scale and tilt. We finally consider reverse refraction and perfect imaging of an Airy beam into a left-handed medium. PMID- 22673415 TI - Scattering of a light wave by a thin fiber on or near a prism: experiment and analytical theory. AB - We have performed an experiment of the scattering of the near field on a prism created by a laser wave, evanescent wave (EW), or plane wave (PW) of an incident angle slightly larger than or smaller than the critical angle, by a thin fiber of subwavelength diameter set above the prism, and we made an analytical theory of an adapted model for the experiment. We have been able to analyze the experimental data exactly by the model theory better than any other theory we have ever known. The importance of the multiple interaction of the wave between the fiber and the surface and also the close similarity of the scattering characteristics between the EW and the PW mentioned above have been acknowledged by the analysis of the data obtained. PMID- 22673416 TI - Penetration effect in gyrotropic slab: theory and applications. AB - Scattering properties of a homogeneous anisotropic slab are investigated at fixed crystal anisotropy axis orientation. The penetration phenomenon for an incident wave propagating tangentially to the crystal surface is discussed. Slab-based nonreciprocal optical devices are proposed. Their operating principles are based on the slab scattering properties, but not on the Faraday effect. Numerical data for an optical isolator and frequency detector are presented. PMID- 22673417 TI - Evaluation of threshold color differences using printed samples. AB - The performances of uniform color spaces and color-difference formulae for predicting threshold color differences were investigated based on visual assessments of 893 pairs of printed color patches under a D65 source. The average DeltaE(ab,10)* of the pairs was 1.1 units. A threshold psychophysical experiment was repeated three times by a panel of 16 observers with normal color vision. The experimental data were used to evaluate nine color-difference formulae and uniform color spaces using the standardized residual sum of squares (STRESS) measure. The results indicated that all formulae and spaces performed very similarly to each other, and outperformed CIELAB for threshold color differences. The chromaticity-discrimination ellipses were used to compare with previous results from small color differences [Color Res. Appl. (2011), doi:10.1002/col.20689], and they agreed with each other, except for the purple color center. PMID- 22673418 TI - General state contrast imaging: an optimized polarimetric imaging modality insensitive to spatial intensity fluctuations. AB - In active polarization imaging, one frequently needs to be insensitive to noninformative spatial intensity fluctuations. We investigate a way of solving this issue with general state contrast (GSC) imaging. It consists in acquiring two scalar polarimetric images with optimized illumination and analysis polarization states, then forming a ratio. We propose a method for maximizing the discrimination ability between a target and a background in GSC images by determining the optimal illumination and analysis states. A further advantage of this approach is to provide an objective way of quantifying the performance improvement obtained by increasing the number of degrees of freedom of a GSC imager. The efficiency of this approach is demonstrated on simulated and real world images. PMID- 22673419 TI - The behavior of the instantaneous Poynting vector of symmetrical laser beams. AB - In this work we investigate the behavior of the instantaneous Poynting vector of symmetrical paraxial laser beams, namely the modification of the instantaneous Poynting vector and the radiation pattern during propagation in free space for a variety of such beams. As an example, we have investigated in detail the behavior of the instantaneous Poynting vector and the radiation pattern of the paraxial Gaussian and Bessel beams. PMID- 22673420 TI - X-ray dark-field imaging modeling. AB - Dark-field images are formed from x-ray small-angle scattering signals. The small angle scattering signals are particularly sensitive to structural variation and density fluctuation on a length scale of several tens to hundreds of nanometers, offering a unique contrast mechanism to reveal subtle structural features of an object. In this study, based on the principle of energy conservation, we develop a physical model to describe the relationship between x-ray small-angle scattering coefficients of an object and dark-field intensity images. This model can be used to reconstruct volumetric x-ray small-angle scattering images of an object using classical tomographic algorithms. We also establish a relationship between the small-angle scattering intensity and the visibility function measured with x-ray grating imaging. The numerical simulations and phantom experiments have demonstrated the accuracy and practicability of the proposed model. PMID- 22673421 TI - Limits on achievable intensity reduction with an optical occulter: comment. AB - An external occulter is used as a means to suppress starlight and enable the observation of faint, Earth-like planets. A recent paper in this journal [J. Opt. Soc. Am. A 28, 1668 (2011)] suggested there were unrecognized limits on starlight intensity suppression with an external occulter. It claimed that, at the level of intensity reduction needed, tips of petal-shaped occulters are too small to be manufactured. We present analysis of that publication's apodization function and show that it is mathematically distinct from the external occulter apodization functions being discussed in the literature. Their broad conclusion that the tips cannot be built is therefore invalid. They suggest that transmitting screens might be superior but do not explain why. We show their transmission function is substantially similar to those in use for the last five years and therefore may not represent an advance in the field. PMID- 22673423 TI - Multichanneled finite-conjugate imaging. AB - Multichanneled imaging systems rely on nonredundant images recorded by an array of low-resolution imagers to enable construction of a high-resolution image. We show how the varying degree of redundancy associated with imaging throughout the imaged volume effects image quality. Using ray-traced image simulations and a metric used as a proxy for human perception, we show that robust recovery of high resolution images can be obtained by avoiding excessive redundancy and that this is a felicitous consequence of typical manufacturing tolerances. PMID- 22673424 TI - Efficient object detection and tracking in video sequences. AB - One of the most important problems in computer vision is the computation of the two-dimensional projective transformation (homography) that maps features of planar objects in different images and videos. This computation is required by many applications such as image mosaicking, image registration, and augmented reality. The real-time performance imposes constraints on the methods used. In this paper, we address the real-time detection and tracking of planar objects in a video sequence where the object of interest is given by a reference image template. Most existing approaches for homography estimation are based on two steps: feature extraction (first step) followed by a combinatorial optimization method (second step) to match features between the reference template and the scene frame. This paper has two main contributions. First, we detect both planar and nonplanar objects via efficient object feature classification in the input images, which is applied prior to performing the matching step. Second, for the tracking part (planar objects), we propose a fast method for the computation of the homography that is based on the transferred object features and their associated local raw brightness. The advantage of the proposed schemes is a fast matching as well as fast and robust object registration that is given by either a homography or three-dimensional pose. PMID- 22673425 TI - Angular acceptance analysis of an infrared focal plane array with a built-in stationary Fourier transform spectrometer. AB - Stationary Fourier transform spectrometry is an interesting concept for building reliable field or embedded spectroradiometers, especially for the mid- and far- IR. Here, a very compact configuration of a cryogenic stationary Fourier transform IR (FTIR) spectrometer is investigated, where the interferometer is directly integrated in the focal plane array (FPA). We present a theoretical analysis to explain and describe the fringe formation inside the FTIR-FPA structure when illuminated by an extended source positioned at a finite distance from the detection plane. The results are then exploited to propose a simple front lens design compatible with a handheld package. PMID- 22673426 TI - Electromagnetic imaging within the contrast-source formulation by means of the multiscaling inexact Newton method. AB - We introduce a new imaging technique that integrates the inexact Newton method into a multifocusing scheme within the contrast-source formulation of the inverse scattering problem. Representative results from an extensive validation concerned with both synthetic and experimental scattering data are reported to assess, also through comparisons, advantages and limitations of the proposed approach in terms of accuracy, robustness, and computational efficiency. PMID- 22673428 TI - Evolutionary algorithm based uniform received power and illumination rendering for indoor visible light communication. AB - In this paper, an evolutionary algorithm based optimization scheme is proposed to realize uniform received power and illumination distribution on the communication floor for fully diffuse indoor visible light communication. Simulation results show that in three distributed lighting configurations, by dynamically modifying the relative optical intensity of transmitters the dynamic range of the received power, referenced against the peak received power, can be reduced to about 40.0% while the uniformity illuminance ratio can be improved up to about 0.70 with the impact to the root mean square delay spread and bandwidth being negligible. Furthermore, the relationship between the field of view of the receivers and the optimization performance is presented as well. PMID- 22673427 TI - Three-dimensional reconstruction of the statistics of heterogeneous objects from a collection of one projection image of each object. AB - An estimation problem for statistical reconstruction of heterogeneous three dimensional objects from two-dimensional tomographic data (single-particle cryoelectron microscope images) is posed as the problem of estimating class probabilities, means, and covariances for a Gaussian mixture where both the mean and covariance are stochastically structured. Both discrete (i.e., classes) and continuous heterogeneity is included. A maximum likelihood solution computed by a generalized expectation-maximization algorithm is presented and demonstrated on experimental images of Flock House Virus. PMID- 22673429 TI - Tomographic imaging with polarized light. AB - We report three-dimensional tomographic reconstruction of optical parameters for the mesoscopic light scattering regime from experimentally obtained datasets by using polarized light. We present a numerically inexpensive approximation to the radiative transfer equation governing the polarized light transport. This approximation is employed in the reconstruction algorithm, which computes two optical parameters by using parallel and perpendicular polarizations of transmitted light. Datasets were obtained by imaging a scattering phantom embedding highly absorbing inclusions. Reconstruction results are presented and discussed. PMID- 22673430 TI - Generalized Gouy phase for focused partially coherent light and its implications for interferometry. AB - The Gouy phase, sometimes called the phase anomaly, is the remarkable effect that in the region of focus a converging wave field undergoes a rapid phase change by an amount of pi, compared to the phase of a plane wave of the same frequency. This phenomenon plays a crucial role in any application where fields are focused, such as optical coherence tomography, mode selection in laser resonators, and interference microscopy. However, when the field is spatially partially coherent, as is often the case, its phase is a random quantity. When such a field is focused, the Gouy phase is therefore undefined. The correlation properties of partially coherent fields are described by their so-called spectral degree of coherence. We demonstrate that this coherence function does exhibit a generalized Gouy phase. Its precise behavior in the focal region depends on the transverse coherence length. We show that this effect influences the fringe spacing in interference experiments in a nontrivial manner. PMID- 22673431 TI - Theoretical limit of localized surface plasmon resonance sensitivity to local refractive index change and its comparison to conventional surface plasmon resonance sensor. AB - In this paper, the theoretical sensitivity limit of the localized surface plasmon resonance (LSPR) to the surrounding dielectric environment is discussed. The presented theoretical analysis of the LSPR phenomenon is based on perturbation theory. Derived results can be further simplified assuming quasistatic limit. The developed theory shows that LSPR has a detection capability limit independent of the particle shape or arrangement. For a given structure, sensitivity is directly proportional to the resonance wavelength and depends on the fraction of the electromagnetic energy confined within the sensing volume. This fraction is always less than unity; therefore, one should not expect to find an optimized nanofeature geometry with a dramatic increase in sensitivity at a given wavelength. All theoretical results are supported by finite-difference time domain calculations for gold nanoparticles of different geometries (rings, split rings, paired rings, and ring sandwiches). Numerical sensitivity calculations based on the shift of the extinction peak are in good agreement with values estimated by perturbation theory. Numerical analysis shows that, for thin (<=10 nm) analyte layers, sensitivity of the LSPR is comparable with a traditional surface plasmon resonance sensor and LSPR has the potential to be significantly less sensitive to temperature fluctuations. PMID- 22673433 TI - Practical fully three-dimensional reconstruction algorithms for diffuse optical tomography. AB - We have developed an efficient fully three-dimensional (3D) reconstruction algorithm for diffuse optical tomography (DOT). The 3D DOT, a severely ill-posed problem, is tackled through a pseudodynamic (PD) approach wherein an ordinary differential equation representing the evolution of the solution on pseudotime is integrated that bypasses an explicit inversion of the associated, ill-conditioned system matrix. One of the most computationally expensive parts of the iterative DOT algorithm, the reevaluation of the Jacobian in each of the iterations, is avoided by using the adjoint-Broyden update formula to provide low rank updates to the Jacobian. In addition, wherever feasible, we have also made the algorithm efficient by integrating along the quadratic path provided by the perturbation equation containing the Hessian. These algorithms are then proven by reconstruction, using simulated and experimental data and verifying the PD results with those from the popular Gauss-Newton scheme. The major findings of this work are as follows: (i) the PD reconstructions are comparatively artifact free, providing superior absorption coefficient maps in terms of quantitative accuracy and contrast recovery; (ii) the scaling of computation time with the dimension of the measurement set is much less steep with the Jacobian update formula in place than without it; and (iii) an increase in the data dimension, even though it renders the reconstruction problem less ill conditioned and thus provides relatively artifact-free reconstructions, does not necessarily provide better contrast property recovery. For the latter, one should also take care to uniformly distribute the measurement points, avoiding regions close to the source so that the relative strength of the derivatives for measurements away from the source does not become insignificant. PMID- 22673432 TI - Objective assessment of image quality. V. Photon-counting detectors and list-mode data. AB - A theoretical framework for detection or discrimination tasks with list-mode data is developed. The object and imaging system are rigorously modeled via three random mechanisms: randomness of the object being imaged, randomness in the attribute vectors, and, finally, randomness in the attribute vector estimates due to noise in the detector outputs. By considering the list-mode data themselves, the theory developed in this paper yields a manageable expression for the likelihood of the list-mode data given the object being imaged. This, in turn, leads to an expression for the optimal Bayesian discriminant. Figures of merit for detection tasks via the ideal and optimal linear observers are derived. A concrete example discusses detection performance of the optimal linear observer for the case of a known signal buried in a random lumpy background. PMID- 22673434 TI - The interim connection space based on human color vision for spectral color reproduction. AB - To improve the spectral image color reproduction accuracy, two novel interim connection spaces (ICSs) were proposed. The dominant structure of spectral power distributions was extracted by principal component analysis for the widely used illuminants and light sources, and then further transformed to three synthetic illuminants. The CIEXYZ tristimulus under two or three synthetic illuminants was employed to construct two novel ICSs. The two ICSs were compared with LabPQR and the ICS with two sets of tristimulus under two real light sources according to the spectral and colorimetric representing accuracy of Munsell and Natural Color System (NCS) chips. The results indicated that the two ICSs proposed in this study outperformed the other two ICSs as a whole. PMID- 22673435 TI - The point-characteristic function, wavefronts, and caustic of a spherical wave refracted by an arbitrary smooth surface. AB - The aim of this paper is to obtain expressions for the k-function, the wavefront train, and the caustic associated with the light rays refracted by an arbitrary smooth surface after being emitted by a point light source located at an arbitrary position in a three-dimensional homogeneous optical medium. The general results are applied to a parabolic refracting surface. For this case, we find that when the point light source is off the optical axis, the caustic locally has singularities of the hyperbolic umbilic type, while the refracted wavefront, at the caustic region, locally has singularities of the cusp ridge and swallowtail types. PMID- 22673436 TI - Generic nonsinusoidal fringe model and gamma calibration in phase measuring profilometry. AB - Gamma distortion is a dominant error source of phase measuring profilometry. It makes a single frequency for the ideal sinusoidal waveform an infinite width of spectrum. Besides, the defocus of the projector-camera system, like a spatial low pass filter, attenuates the amplitudes of the high-frequency harmonics. In this paper, a generic distorted fringe model is proposed, which is expressed as a Fourier series. The mathematical model of the harmonic coefficients is derived. Based on the proposed model, a robust gamma calibration method is introduced. It employs the multifrequency phase-shifting method to eliminate the effect of defocus and preserve the influence of gamma distortion. Then, a gamma correction method is proposed to correct the gamma distortion with the calibrated gamma value. The proposed correction method has the advantage of high signal-to-noise ratio. The proposed model is verified through experiments. The results confirm that the phase error is dependent on the defocus and the pitch. The proposed gamma calibration method is compared with the state of the art and proves to be more robust to pitch and defocus variations. After adopting the proposed gamma correction method, the phase precision is much enhanced with higher quality in the measured surfaces. PMID- 22673437 TI - Resolution of aplanatic solid immersion lens based microscopy. AB - We study the resolution of a subsurface microscopy system based on the use of an aplanatic solid immersion lens. Resolution limits under various criteria are calculated theoretically as well as numerically. Images of combinations of dipoles of various orientations are considered. Both lateral and longitudinal resolutions are studied. The theoretical criteria are compared against the visually resolvable simulated images of the dipoles. The observations are explained explicitly through a detailed analysis of the dyadic Green's function. A new resolution criterion is also proposed, which provides a very accurate estimate of the resolution limits. PMID- 22673438 TI - Fresnel diffraction at an opaque strip expressed by means of asymptotic representations of Fresnel integrals. AB - The paper presents an asymptotic expression of relative intensity distribution in a Fresnel diffraction pattern at an opaque straight strip illuminated with a spherical wave. The asymptotic expression is used in an analysis showing an area of validity where the asymptotic expression reduces to an asymptotic expression of relative intensity distribution in a Fresnel diffraction at a half plane. The area of validity is defined through width of the geometrical shadow in a Fresnel diffraction pattern at an opaque straight strip and distance of a point under study to the center of the Fresnel diffraction pattern. Within this area, relative intensity in the Fresnel diffraction pattern at an opaque straight strip shows sinusoidal behavior, which can be used in easy location of maxima or minima of the relative intensity. The result of the analysis is supported by experiments realized in the area of validity and outside it. PMID- 22673439 TI - Scattering-induced changes in the degree of polarization of a stochastic electromagnetic plane-wave pulse. AB - The scattering of a stochastic electromagnetic plane-wave pulse on a deterministic spherical medium is investigated. An analytical formula for the degree of polarization (DOP) of the scattered field in the far zone is derived. Letting pulse duration T(0) -> infinity, our formula can be applied to study the scattering of a stationary stochastic electromagnetic light wave. Numerical results show that the DOP of the far zone field is closely determined by the size of the spherical medium when the incident field is a stochastic electromagnetic plane-wave pulse. This is much different from the case when the incident field is a stationary stochastic electromagnetic light wave, where the DOP of the far zone field is independent of the size of the medium. One may obtain the information of the spherical medium by measuring the scattering-induced changes in the DOP of a stochastic electromagnetic plane-wave pulse. PMID- 22673440 TI - Atmospheric spectral model and theoretical expressions of irradiance scintillation index for optical wave propagating through moderate-to-strong non Kolmogorov turbulence. AB - A new atmospheric spectral model and expressions of irradiance scintillation index are derived theoretically for optical wave propagating through moderate-to strong non-Kolmogorov turbulence. They are developed under Andrews' assumption that small-scale irradiance fluctuations are modulated by large-scale irradiance fluctuations of the wave, and the geometrical optics approximation is adopted for mathematical development. A wide range of turbulence strength is considered instead of a limited range for weak turbulence. The atmospheric spectral model has a spectral power law value in the range of 3 to 4 instead of the standard power law value of 11/3. Numerical calculations are conducted to analyze the influences of spectral power law and turbulence strength. PMID- 22673441 TI - Tight focusing properties of hybridly polarized vector beams. AB - We theoretically investigate the tight focusing properties of hybridly polarized vector beams. Some numerical results are obtained to illustrate the intensity, phase, and polarization of tightly focused hybridly polarized vector beams. It is shown that the shape of the focal pattern may change from an elliptical beam to a ring focus with increasing radial index. The phase distribution around the tightly focused ring is shown to be the helical phase profile, indicating that the radial-variant spin angular momentum of hybridly polarized vector beams can be converted into the radial-variant orbital angular momentum. PMID- 22673442 TI - Overall gloss evaluation in the presence of multiple cues to surface glossiness. AB - Human observers use the information offered by various visual cues when evaluating the glossiness of a surface. Several studies have demonstrated the effect of each single cue to glossiness, but little has been reported on how multiple cues are integrated for the perception of surface gloss. This paper reports on a psychophysical study with real stimuli that are different regarding multiple visual gloss criteria. Four samples were presented to 15 observers under different conditions of illumination in a light booth, resulting in a series of 16 stimuli. Through pairwise comparisons, an overall gloss scale was derived, from which it could be concluded that both differences in the distinctness of the reflected image and differences in luminance affect gloss perception. However, an investigation of the observers' strategy to evaluate gloss indicated a dichotomy among observers. One group of observers used the distinctness-of-image as a principal cue to glossiness, while the second group evaluated gloss primarily from differences in luminance of both the specular highlight and the diffuse background. It could therefore be questioned whether surface gloss can be characterized with one single quantity, or that a set of quantities is necessary to describe the gloss differences between objects. PMID- 22673443 TI - Transverse electric and transverse magnetic pulsed-beam decomposition of time dependent aperture fields. AB - The present contribution is concerned with applying beam-type expansion to a planar aperture time-dependent (TD) electromagnetic field in which the propagating elements, the electromagnetic pulsed-beams, are a priori decomposed into transverse electric (TE) and transverse magnetic (TM) field polarizations. The propagating field is described as a discrete superposition of tilted, shifted, and delayed TE and TM electromagnetic pulsed-beam propagators over the frame spectral lattice. These waveobjects are evaluated by using TD plane-wave spectral representations. Explicit asymptotic expressions for electromagnetic isodiffracting pulsed-quadratic beam propagators are presented, as well as a numerical example. PMID- 22673444 TI - An inverse light scattering technique for morphological characterization of irregular particles based on the Gaussian-random-sphere model. AB - The Gaussian-random-sphere model is employed for morphological characterization of nonspherical, irregular particles using an inverse light scattering technique. The synthetic measurement data consist of reduced scattering spectra caused by an aggregate of irregular particles randomly oriented in turbid media and are generated using the discrete dipole approximation. The proposed method simultaneously retrieves the concentration and shape parameters of particles using the data collected at multiple wavelengths. The performance of the inverse algorithm is tested using noise-corrupted data, in which up to 50% noise may be added to the observed scattering spectra. PMID- 22673445 TI - Coupling interactions in electromagnetic scattering from finite array of cavities with stratified dielectric coating. AB - The coupling interactions in electromagnetic scattering from a finite array of two-dimensional identical cavities engraved in a perfectly electric conducting screen covered with stratified dielectric coating are presented using an algorithm based on the hybrid finite element-boundary integral method. The solution to the scattering from a finite array of cavities is approximated using the array factor method, which does not take into account the coupling between the cavities, and is compared to the recently developed finite element-boundary element method to demonstrate the importance of the inclusion of the coupling effect. Dependence of the coupling interactions between the cavities on various parameters such as separation periods, incident angle of the plane-wave excitation, and permittivity and thickness of the dielectric coating is demonstrated quantitatively through several numerical examples. PMID- 22673446 TI - Determination of first-order derivatives of skew ray at aspherical surface. AB - A set of algorithms is proposed for determining the first-order derivatives of a skew ray with respect to all the independent variables of an aspherical boundary surface in a general 3D optical system. Ellipsoidal, paraboloidal, hyperboloidal, and cylindrical boundary surfaces are given as examples. The proposed method has important applications in the analysis of aspherical surfaces and enables a detailed understanding of a wide variety of optical effects, including reflection and refraction, the modulation transfer function, and aberrations. PMID- 22673447 TI - Backscattering measurements from double-scale randomly rough surfaces. AB - We present experimental measurements of light backscattered from double-scale randomly rough surfaces (oceanlike surfaces) with different statistical parameters illuminated at small and large angles of incidence. The surfaces are composed of a small-scale roughness superimposed on a slowly (large-scale) varying surface. The large-scale surfaces are diamond-machined periodic surfaces made on aluminum substrates and have either a sinusoidal or a Stokes wave profile. The small-scale roughness is added with lithographic techniques, and the surfaces are then gold coated. For a linearly polarized incident beam, it is found that the backscattered light is strongly depolarized mainly at small angles of incidence and strong shadowing effects are present for large angles of incidence (theta(inc) > 60 degrees ). PMID- 22673448 TI - Multiple-scattering model for the coherent reflection and transmission of light from a disordered monolayer of particles. AB - Using a multiple-scattering formalism, we derive closed-form expressions for the coherent reflection and transmission coefficients of monochromatic electromagnetic plane waves incident upon a two-dimensional array of randomly located spherical particles. The calculation is performed within the quasi crystalline approximation, and the statistical correlation among the particles is assumed to be given simply by a correlation hole. In the resulting model, the size of the spheres and the angle of incidence are both unrestricted. The final formulas are relatively simple, making the model suitable for a straightforward interpretation of optical-sensing measurements. PMID- 22673449 TI - Dynamic coding of temporal luminance variation. AB - The range of variation in environmental stimuli is much larger than the visual system can represent. It is therefore sensible for the system to adjust its responses to the momentary input statistics of the environment, such as when our pupils contract to limit the light entering the eye. Previous evidence indicates that the visual system increasingly centers responses on the mean of the visual input and scales responses to its variation during adaptation. To what degree does adaptation to a stimulus varying in luminance over time result in such adjustment of responses? The first two experiments were designed to test whether sensitivity to changes in the amplitude and the mean of a 9.6 degrees central patch varying sinusoidally in luminance at 0.6 Hz would increase or decrease with adaptation. This was also tested for a dynamic peripheral stimulus (random patches rotating on the screen) to test to what extent the effects uncovered in the first two experiments reflect retinotopic mechanisms. Sensitivity to changes in mean and amplitude of the temporal luminance variation increased sharply the longer the adaptation to the variation, both for the large patch and the peripheral patches. Adaptation to luminance variation leads to increased sensitivity to temporal luminance variation for both central and peripheral presentation, the latter result ruling retinotopic mechanisms out as sole explanations for the adaptation effects. PMID- 22673450 TI - Speckle contrast of the sum of N partially correlated speckle patterns. AB - In this paper a general method is presented for calculating the theoretical speckle contrast of a sum of correlated speckle patterns, motivated by the need to suppress the presence of speckle in laser projection displays. The method is applied to a specific example, where correlated speckle patterns are created by sequentially passing light through partially overlapping areas on a diffuser, before being projected onto a screen. This design makes it possible to find a simple expression for the correlation between speckle patterns. When the set of correlations involves symmetry, it is shown that the expression for the speckle contrast becomes simpler. The difference in performance between discretely and continuously varying speckle patterns is also investigated. In an example with speckle reduction by a rotating sinusoidal grating, it is found that continuous variation gives a speckle contrast that is 0.61 times the contrast obtained by discretely summing the maximum number of independent patterns. PMID- 22673451 TI - Short term exposure to attractive and muscular singers in music video clips negatively affects men's body image and mood. AB - Viewing idealized images has been shown to reduce men's body satisfaction; however no research has examined the impact of music video clips. This was the first study to examine the effects of exposure to muscular images in music clips on men's body image, mood and cognitions. Ninety men viewed 5 min of clips containing scenery, muscular or average-looking singers, and completed pre- and posttest measures of mood and body image. Appearance schema activation was also measured. Men exposed to the muscular clips showed poorer posttest levels of anger, body and muscle tone satisfaction compared to men exposed to the scenery or average clips. No evidence of schema activation was found, although potential problems with the measure are noted. These preliminary findings suggest that even short term exposure to music clips can produce negative effects on men's body image and mood. PMID- 22673452 TI - Tunable, dynamic and electrically stimulated lectin-carbohydrate recognition on a glycan-grafted conjugated polymer. AB - An electroactive platform for multivalent, reversible and electrically stimulated lectin-carbohydrate recognition based on mannose-functionalized conjugated polymer is reported and tuned by electrocopolymerization of mixture of tri(ethylene glycol)-functionalized EDOT and its alpha-mannose conjugate. PMID- 22673453 TI - Sleep quality and aerobic training among menopausal women--a randomized controlled trial. AB - BACKGROUND: Menopause is associated with poor sleep quality and daytime sleepiness, which may lead to impaired quality of life and impaired functioning in daily activities. OBJECTIVE: To study whether exercise training improves sleep quality or decreases the amount of night time hot flushes among menopausal women with vasomotor symptoms. STUDY DESIGN: A randomized controlled trial. Sedentary women (N=176) aged 43-63 years with menopausal symptoms were randomized to a six month unsupervised aerobic training intervention (50 min 4 times per week) or a control group. Both groups attended lectures on physical activity and health once a month. MAIN OUTCOME MEASURES: Sleep quality and the amount of hot flushes disturbing sleep. The women reported daily via mobile phone whether hot flushes had disturbed their sleep and how they had slept (scale 1-5). Responses received by mobile phone over the 6-month period totaled on average 125 (5.2 per week) responses per participant. RESULTS: At baseline there was no difference between the groups in the demographic variables. Sleep quality improved significantly more in the intervention group than in the control group (OR 1.02; 95% CI=1.0 1.05, p=0.043). The odds for sleep improvement were 2% per week in the intervention group and a decrease of 0.5% per week in the control group. The amount of hot flushes related to sleep diminished (p=0.004) by the end of the intervention. CONCLUSIONS: Aerobic training for 6 months may improve sleep quality and reduce hot flushes among symptomatic menopausal women. PMID- 22673454 TI - Failure morphology of all-ceramic prostheses. AB - The aim of this study is to investigate the internal morphology of all-ceramic prostheses before seating. Micro X-ray CT was used to inspect three dimensionally the locations and sizes of pores within experimentally fabricated all-ceramic crowns as well as measure the veneer and core thickness. Scanning electron microscopy (SEM) was used to examine the fracture sites of clinically failed prostheses. Micro X-ray CT analysis revealed the distribution patterns of pores within the all-ceramic prostheses, and SEM fractographic analysis indicated a strong relationship between the existence of pores and crack propagation. Therefore, micro X-ray CT is a useful tool for nondestructive inspection of the internal morphology of all-ceramic prostheses to identify the critical defects before seating. PMID- 22673456 TI - Topical fluoride application is able to reduce acid susceptibility of restorative materials. AB - This study aimed to investigate the effect of topical fluoride application on the acid susceptibility of restorative materials. Four restorative materials were investigated in this study: 2 composite resins (Tetric EvoCeram and Filtek Silorane), a polyacid-modified resin composite (Dyract Extra), and a conventional glass-ionomer cement (Ketac Fil Plus). The samples were treated once with 1 of 8 different fluoride solutions (TiF4, NaF, AmF, and SnF2, each at native pH or pH 4) for 3 min or remained untreated (control). The samples were then eroded by citric acid (pH 2.6) for 5 days (6*1 min daily). Erosive substance loss, surface topographic and compositional changes were investigated using surface profilometry, scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDS), respectively, after fluoride pretreatment and after erosion. The results indicate high-concentrated AmF solution at native pH was effective in inhibiting erosion in the conventional glass-ionomer cement and polyacid-modified resin composite. PMID- 22673455 TI - Micro-CT evaluation of in vivo osteogenesis at implants processed by wire-type electric discharge machining. AB - Titanium surfaces processed by wire-type electric discharge machining (EDM) are microfabricated surfaces with an irregular morphology, and they exhibited excellent in vitro bone biocompatibility. In this study, the efficiency of in vivo osteogenesis on EDM surfaces was investigated by surgically placing screw shaped EDM-processed and machined-surface implants into the femurs of four Japanese white rabbits. The volume and process of new bone formation were evaluated by an X-ray micro-CT scanner, coupled with histopathological observations at 1, 2, and 4 weeks post-implantation. Before surgical implantation, the surface topography and contact angle of each implant surface were examined. Bone formation increased over time on both implant surfaces, with both implant types yielding statistically equivalent bone volume at 4 weeks post implementation. However, at 1 week post-implantation, amount of new bone at EDM processed implant was markedly greater than that at machined-surface implant. Moreover, new bone appeared to initiate directly from the EDM surfaces, while new bone appeared to generate from pre-existing host bone to the machined surfaces. Thus, EDM seemed to be a promising method for surface modification of titanium implants to support enhanced osteogenesis. PMID- 22673457 TI - Interfacial shear bond strength between different base metal alloys and five low fusing feldspathic ceramic systems. AB - This study compared the bond strength between metal alloys and 5 ceramic systems. Ceramic systems (Vita VMK68, Ivoclar IPSd. SIGN, Ceramco II, Matchmaker and Finesse) were fired onto either Ni-Cr or Co-Cr base metal alloy. Metal-ceramic interfaces were subjected to shear loading until failure. The ceramic type significantly affected the bond strength results (p<0.05). For Ni-Cr alloy, the results ranged between 15.4-25.3 MPa and for Co-Cr alloy between 13.3-19.0 MPa. The highest mean bond strength value was obtained with the combination of Ni-Cr alloy-Ceramco II (25.3 MPa), the lowest bond strength was received from the combination of Co-Cr alloy-Ivoclar IPS d.SIGN ceramic (13.3 MPa). Adhesive failures between metal and ceramic were significantly more frequent with Ni-Cr alloy (31 out of 50) than with Co-Cr (20 out of 50) (p<0.05). Ceramco II presented the highest bond strength with both Ni-Cr and Co-Cr being significantly different from one another. PMID- 22673458 TI - Evaluation of denture base resin after disinfection method using reactive oxygen species (ROS). AB - The effects of certain disinfectants on the stability of a polymethyl methacrylate denture base resin were investigated, including those of a novel disinfection method using reactive oxygen species (ROS). The surface roughness and flexural strength were analyzed to assess the effects of the disinfectants on material properties. The following disinfectants were tested: 5% sodium hypochlorite, 70% alcohol, and ROS. Furthermore, the attachment of Candida albicans to the resin surface was investigated. The disinfection method using sodium hypochlorite significantly increased the surface roughness and decreased flexural strength. The surface roughness and flexural strength of the ROS-treated specimens did not significantly differ from those of the control specimens, and the ROS-treated specimens exhibited diminished Candida attachment. These results demonstrate that the ROS disinfection method preserves acceptable material stability levels in polymethyl methacrylate resins. PMID- 22673459 TI - 3-dimensional composite scaffolds consisting of apatite-PLGA-atelocollagen for bone tissue engineering. AB - We fabricated 3-dimensional scaffolds consisting of biodegradable poly(D, L lactide-co-glycolic acid)(PLGA)(75/25) with hydroxyapatite particles containing atelocollagen (aAC). The aim of this study was to evaluate this new type of scaffold in regard to its basic properties and biocompatibility. Characterization of the obtained scaffolds was performed to know the porosity, shrinkage, diametral tensile strength, and biocompatibility. Composite scaffolds made of PLGA with hydroxyapatite particles containing atelocollagen (PL-aAC) showed a greater strength and stability than PLGA scaffolds. PL-aAC also exhibited superior performance in terms of cell attachment and proliferation as compared to PLGA, while histological findings showed that PL-aAC had an excellent response toward soft tissues. Our results strongly suggest that PL-aAC is more useful for cell transplantation as compared to PLGA for bone tissue engineering. PMID- 22673460 TI - Initial attachment of human oral keratinocytes cultured on zirconia or titanium. AB - Initial attachment of human oral keratinocytes (HOKs) cultured on mirror-surfaced commercially pure titanium (Ti) or yttria-stabilized tetragonal zirconia polycrystals (TZP) was investigated. Numbers of viable attached HOKs, their mRNAs and proteins expression of laminin gamma2 and integrin beta4 were evaluated using the WST-1 assay, quantitative real-time PCR and enzyme-linked immunosorbent assay, respectively. Localization of laminin gamma2 and integrin beta4 was observed using immunofluorescent staining. Cell spreading was evaluated by measuring the perimeter of actin on fluorescent stained images, and cell morphology was examined using scanning electron microscopy. At 1 h TZP elicited less of initial attachment than Ti in terms of mRNAs expression and proteins expression of laminin gamma2 and integrin beta4 (p<0.05). However, at 48 h TZP was showed similar initial attachment in comparison to Ti. Therefore, it was suggested that TZP has a potential to form epithelial attachment like Ti. PMID- 22673462 TI - Measuring the effects of water immersion conditions on the durability of fiber reinforced hybrid composite resin using static and dynamic tests. AB - The present study was designed to measure the durability of glass fiber reinforced hybrid resins (FRC) in clinical applications. Accordingly, we studied the effects of static and dynamic loading as well as temperature changes inside the oral cavity, a moist environment, on the bending strength of FRC. The bending strength was measured using several tests, including an open-air bending strength test (AE), a 24-h water immersion test (WC1D), a 2-year water immersion test (WC2Y), a thermal cycling test (TC), a repeated in-water impact test at 37 degrees C/10(5) (WI37), and a repeated in-water impact test at 55 degrees C/10(5) (WI55). The following tests are ordered from greatest to least with respect to GF's bending strength: AE, WI37, WI55, WC1D, WC2Y, and TC. Likewise, the following tests are ordered from greatest to least with respect to EV's bending strength: AE, WC1D, WC2Y, WI37, WI55, and TC. PMID- 22673461 TI - ESR investigation of ROS generated by H2O2 bleaching with TiO2 coated HAp. AB - It is well known that clinical bleaching can be achieved with a solution of 30% hydrogen peroxide (H2O2) or H2O2/titanium dioxide (TiO2) combination. This study examined the hypothesis that TiO2 coated with hydroxyapatite (HAp-TiO2) can generate reactive oxygen species (ROS). ROS are generated via photocatalysis using electron spin resonance (ESR). The bleaching properties of HAp-TiO2 in the presence of H2O2 can be measured using hematoporphyrin litmus paper and extracted teeth. We demonstrate that superoxides (O2(*-)) and hydroxyl radicals (HO(*)) can be generated through excitation of anatase TiO2, rutile TiO2, anatase HAp-TiO2, and rutile HAp-TiO2 in the presence of H2O2. The combination of R HAp-TiO2 with H2O2 produced the highest level of HO(*) generation and the most marked bleaching effects of all the samples. The superior bleaching effects exhibited by R HAp TiO2 with H2O2 suggest that this combination may lead to novel methods for the clinical application of bleaching treatments. PMID- 22673463 TI - Microfractures in metal-ceramic and all-ceramic implant-supported fixed dental prostheses caused by superstructure fixation. AB - The effect of ceramic veneering on the passivity of fit of cast metal and CAD/CAM fabricated zirconia ceramic implant-supported three-unit cement-retained restorations was investigated, as well as the effect of misfit stress on the marginal integrity of ceramic veneers. Superstructures were fabricated using cast metal or by CAD/CAM milling of presintered or HIP zirconia ceramic (n=10). Before and after veneering, strain gages were used to measure in vitro the strain developed in all the restorations as a result of superstructure fixation. Fluorescent penetrant method was used to detect microcracks developed in ceramic veneers. Cast frameworks showed significantly higher strain values than CAD/CAM frameworks (p=0.000). Veneering significantly increased strain development in all CAD/CAM frameworks (p=0.000). Compared to zirconia ceramic restorations, significantly more microcracks were observed in cast restorations (p=0.000) both before and after superstructure fixation. PMID- 22673465 TI - In vitro permeability of etch-and-rinse and self-etch adhesives used for immediate dentin sealing. AB - To investigate the permeability of deep dentin following immediate sealing with different etch-and-rinse and self-etch adhesives (Single Bond 2, Adper Prompt L Pop, Clearfil Protect Bond, Clearfil S3 Bond, G-Bond) and a dentin desensitizer (Gluma). Fluid-transport model was used to measure fluid conductance during and after application of adhesives. Polyvinylsiloxane impressions of bonded dentin were taken to monitor fluid transudation from the surface of the adhesives. The area and number of dentinal fluid droplets and/or blisters were calculated using image analysis. None of the adhesives were able to block fluid conductance completely. The fluid conductance values of the adhesives displayed the following statistical ranking (p<0.05): G-Bond<=Clearfil Protect Bond0.548). No significant differences in the distribution of active and latent TrPs in the analyzed muscles between groups were found. Active TrPs in the upper trapezius, infraspinatus, levator scapulae, and extensor carpi radialis brevis muscles were the most prevalent in both groups. Significant differences in referred pain areas between muscles (P<0.001) were found; pectoralis major, infraspinatus, upper trapezius, and scalene muscles showed the largest referred pain areas (P<0.01), whereas the temporalis, masseter, and splenius capitis muscles showed the smallest (P<0.05). The combination of the referred pain from TrPs reproduced the overall clinical pain area in all participants. CONCLUSIONS: Blue-collar and white-collar workers exhibited a similar number of TrPs in the upper quadrant musculature. The referred pain elicited by active TrPs reproduced the overall pain pattern. The distribution of TrPs was not significantly different between groups. Clinicians should examine for the presence of muscle TrPs in blue-collar and white-collar workers. PMID- 22673485 TI - Comparing pain modulation and autonomic responses in fibromyalgia and irritable bowel syndrome patients. AB - OBJECTIVES: Past studies confirm that patients with fibromyalgia (FM) and irritable bowel syndrome (IBS) show similar pain processing dysfunctions, such as reduced pain inhibition and aberrant autonomic nervous system (ANS) responses. However, patients with FM and IBS have rarely been investigated in the same study. The aim of the present study, therefore, was to compare descending pain inhibition, pain sensitivity, and ANS reactivity to pain in FM, IBS, and healthy controls (HC). METHODS: Female patients with FM (n=10), IBS (n=13), and HCs (n=10) were exposed to multiple cold water (12 degrees C) immersions to study pain sensitivity and descending pain inhibition. Heart rate variability was also assessed during immersions. RESULTS: Pain intensity scores were highest in FM, intermediate in IBS, and smallest in HCs. In contrast, pain inhibition was absent in FM, intermediate in IBS, and strongest in HCs. Importantly, controlling for differences in pain inhibition abolished group differences in pain sensitivity. Heart rate variability analyses confirmed that, in response to mild levels of pain, patients with FM showed greater sympathetic activity whereas HCs showed greater parasympathetic activity. Patients with IBS showed intermediate ANS responses. DISCUSSION: Our results confirm the presence of graded levels of somatic hyperalgesia across patients with IBS and FM. A similar pattern of result was observed for pain inhibitory dysfunctions. These pain processing changes were accompanied by abnormal autonomic responses, which maintained patients (principally patients with FM) in a state of sympathetic hyperactivity. Results suggest that patients with IBS and FM may present common, but graded, pain processing and autonomic dysfunctions. PMID- 22673487 TI - mild Interlaminar decompression for the treatment of lumbar spinal stenosis: procedure description and case series with 1-year follow-up. AB - OBJECTIVES: mild interlaminar decompression is a minimally invasive procedure for the treatment of patients with symptomatic lumbar spinal stenosis. This report describes the mild procedure and presents 1-year clinical outcomes of patients treated with mild. METHODS: mild treats lumbar spinal stenosis by removing portions of the lamina and ligamentum flavum to restore space in the lumbar spine. The procedure is conducted under fluoroscopic guidance, and is performed with moderate sedation. One-year follow-up was obtained for 17 patients treated with the mild procedure. Clinical evaluations were conducted at baseline and at 1 year follow-up with the 10-point Visual Analog Score and Oswestry Disability Index. RESULTS: mild treatments were completed with no major device-related or procedure-related complications. The baseline mean Visual Analog Score of 7.6 improved at 1 year after the procedure to 2.3, a decrease of 5.4 cm points, or an average percentage decrease of 70.0%. Average baseline Oswestry Disability Index of 48.4 improved to 21.7 at 1 year, an improvement of 26.6 points. DISCUSSION: The mild technique provides an attractive early option for the treatment of symptomatic lumbar spinal stenosis after failed injection therapy, but before more invasive surgical treatment. For 17 patients with 1-year follow-up, the mild procedure provided significant pain relief and increased mobility. This procedure leaves no implants behind, and therefore does not limit subsequent, more invasive procedures that require implants. PMID- 22673486 TI - Is botulinum toxin A effective for the treatment of plantar fasciitis? AB - OBJECTIVES: Botulinum toxin A (BoNT-A) is used as an alternative treatment for chronic orthopedic conditions. This study was conducted to investigate the efficacy and safety of BoNT-A on pain and functional outcome in patients with chronic plantar fasciitis. METHODS: In this short-term, randomized, multicenter, double-blind, placebo-controlled study, patients (N=40) were randomized to receive 200 units of BoNT-A (Dysport) or saline placebo. The injection was administered in a fan-shaped manner directly at the calcaneal origin of the plantar fascia. The primary outcome measure was the proportion of responders at week 6 [>=50% decrease from baseline in pain score (visual analog scale) while moving during the previous 48 h). Global assessments were performed by the patient and physician at each visit up to week 18. RESULTS: More patients in the BoNT-A group achieved a response at week 6 (25% vs. 5% for placebo; P=0.18). Differences between treatments were in favor of BoNT-A on secondary measures of pain, but did not reach statistical significance. In the BoNT-A group, 52.7% (vs. 40% for placebo) assessed their condition as slightly/significantly improved at week 6. At study endpoint (week 18), 63.1% of the BoNT-A group perceived an improvement versus 55% of the placebo group. There was no difference in global assessment between physician and patient. No adverse events related to treatment were noted. DISCUSSION: There is a need for larger, prospective, long-term, placebo-controlled studies to fully establish the role of BoNT-A for the treatment of plantar fasciitis. PMID- 22673488 TI - A case of potential treatment of remote pain after sacral nerve stimulation for chronic urinary retention. AB - OBJECTIVE: A case is presented in which a 58-year-old man developed a potential unintended and durable treatment of pain at remote sites (cervical region and low back) after sacral nerve stimulation for chronic urinary retention. METHODS: Proper placement of the electrodes in the S3 foramen was confirmed by physiological response and fluoroscopy. RESULTS: Potential causality was shown by recurrent pain with the stimulators turned off and abatement of pain with the stimulators turned on. DISCUSSION: The current case presents a potential example of neurological crosstalk and highlights the inherent complexity in human neural physiology. Further research may reveal novel treatment strategies for patients with voiding dysfunction and chronic pain syndromes. PMID- 22673489 TI - Systematic review of the quality and generalizability of studies on the effects of opioids on driving and cognitive/psychomotor performance. AB - INTRODUCTION: The effect of opioids on driving performance has been much debated. Driving is a complex task requiring integration of psychomotor, cognitive, motor and decision-making skills, visual-spatial abilities, divided attention, and behavioral and emotional control. The objective of this systematic review was to assess the quality of studies and to revisit the concept that patients on stable opioids are safe to drive as it applies to everyday practice. METHODS: We searched MEDLINE, EMBASE, PSYCinfo, CENTRAL, TRANSPORT, CINAHL, reference lists of retrieved articles and narrative reviews, for studies on chronic cancer and noncancer pain patients on opioids, tested by driving, driving simulator, or cognitive/psychomotor tests. Methodological quality was assessed with Methodological Index for Nonrandomized Studies, cognitive/psychomotor tests were appraised regarding their sensitivity and validation, and whether confounding variables potentially affecting the study conclusions were recorded. The results were analyzed both quantitatively and qualitatively. RESULTS: We included 35 studies (2044 patients, 1994 controls), 9% of the studies were of poor, 54% of fair, and 37% of high quality; 3 quarters of the studies used high sensitivity cognitive tests. Amount and dose of opioids varied largely in many studies. Mean number of possible but unreported confounders was 2.2 (range, 0 to 4), relating to failure of the studies to mention co-prescriptions with psychotropic effects, pain severity, sleep disorder or daytime somnolence, and/or significant depressive or anxiety-related problems. INTERPRETATION: The commonly held concept that "chronic pain patients on stable opioids are safe to drive" cannot be generalized to all such patients in everyday practice, but may be applicable only to a subset who meet certain criteria. PMID- 22673490 TI - Calcineurin-inhibitor pain syndrome. AB - BACKGROUND: There has been increased recognition of calcineurin, a phosphoprotein serine/threonine phosphatase enzyme, in the regulation of many physiologic systems. Calcineurin mediates activation of lymphocytes, which play a role in immune response. Widely distributed in the central nervous system, calcinuerin also plays an important role in sensory neural function, via its role in the regulation of newly discovered 2-pore potassium channels, which greatly influence neuronal resting membrane potentials. Calcinuerin inhibition is the mechanism of action of immunomodulatory drugs such as cyclosporine and tacrolimus, which are widely used in transplantation medicine to prevent rejection. While important for immunosuppression, the use of calcineurin inhibitors has been associated with the development of a new pain syndrome called the calcineurin pain syndrome, which appears to be an untoward complication of the interruption of the physiologic function of calcineurin. METHODS: This is a narrative review focusing on the epidemiology, pathophysiology, characterization of a newly recognized pain syndrome associated with the use of calcineurin inhibitors. RESULTS: The use of immunosuppressants however is associated with several well-known toxicities to which the calcineurin pain syndrome can be added. The development of this syndrome most likely involves altered nociceptive processing due to the effect of calcineurin inhibition on neuronal firing, as well as effects of calcineurin on vascular tone. The most striking aspect of the treatment of this syndrome is the response to calcium channel blockers, which suggest that the effects of calcineurin inhibition on vascular tone play an important role in the development of the calcineurin pain syndrome. CONCLUSION: The calcineurin syndrome is a newly recognized complication associated with the use of calcineurin inhibitors. There is no standard therapy at this time but anecdotal reports suggest the effectiveness of calcium channel blockers. PMID- 22673491 TI - Immunopathology in influenza virus infection: uncoupling the friend from foe. AB - Influenza epidemics and pandemics cause significant morbidity and mortality worldwide associated with severe immunopathology in the lung, and the mechanisms of such immunopathogenesis still remain poorly understood. While human studies help to understand influenza immunopathology, they provide only limited mechanistic information. On the other hand, recent studies using experimental animal models have significantly enhanced our understanding of the complex mechanisms involved in the immunopathogenesis during primary influenza or influenza-associated bacterial superinfection. This includes the involvement of acute inflammatory responses (macrophages, neutrophils, dendritic cells, toll like receptors, cytokines, chemokines), CD4 and CD8 T cells, tissue remodeling processes, and contribution of bacterial superinfection. In particular, progress has been made in uncoupling the mechanisms that are involved in both anti-viral host defense and in immunopathogenesis from those that solely contribute to lung immunopathology. Uncoupling such events will facilitate the discovery of new intervention strategies to treat pulmonary immunopathology associated with influenza infection. PMID- 22673492 TI - MBL serum levels in patients with sepsis correlate with thyroid function but not with outcome. PMID- 22673493 TI - Management of central venous gradient using excimer laser lead extraction of chronic indwelling pacemaker leads in the setting of ipsilateral arteriovenous fistula. AB - Device therapy is becoming common in those patients with renal insufficiency. Coexisting need for arteriovenous (AV) fistula placement is often contemplated relative to device placement. We describe the excimer laser lead extraction of a malfunctioning chronic atrial pacemaker lead ipsilateral to an AV fistula. PMID- 22673494 TI - Ogmocotyle ailuri (Price, 1954) (Digenea: Notocotylidae) found in the Japanese monkey, Macaca fuscata. AB - Several dozens of small trematodes were found in the small intestine of a Japanese monkey, Macaca fuscata, that was captured in Sendai City, Miyagi Prefecture, Japan. The trematode was identified as Ogmocotyle ailuri. This is the first case of a Japanese monkey infected with Ogmocotyle trematodes, and a new host record for O. ailuri. PMID- 22673495 TI - Retrospective analysis of sheep scrapie by western blotting with formalin-fixed paraffin-embedded (FFPE) tissues. AB - An abnormal isoform of prion protein (PrP(Sc)) was extracted from formalin-fixed paraffin-embedded (FFPE) tissues from sheep and analyzed by western blotting. PrP(Sc) immunoreactivity against anti-PrP monoclonal antibody T2, which recognizes discontinuous PrP sequences, differed amongst individual scrapie sheep cases. This may reflect structural differences in PrP(Sc) that have been formalin fixed prior to their extraction. This study indicates that western blotting by using FFPE tissues is useful for the retrospective analysis of transmissible spongiform encephalopathies in which only formalin-fixed samples are available and in conducting transmissible spongiform encephalopathies surveillance where freezing system is insufficient. PMID- 22673496 TI - SDF-1 in myocardial repair. AB - Stem cell therapy for the prevention and treatment of cardiac dysfunction holds significant promise for patients with ischemic heart disease. Excitingly early clinical studies have demonstrated safety and some clinical feasibility, while at the same time studies in the laboratory have investigated mechanisms of action and strategies to optimize the effects of regenerative cardiac therapies. One of the key pathways that has been demonstrated critical in stem cell-based cardiac repair is (stromal cell-derived factor-1) SDF-1:CXCR4. SDF-1:CXCR4 has been shown to affect stem cell homing, cardiac myocyte survival and ventricular remodeling in animal studies of acute myocardial infarction and chronic heart failure. Recently released clinical data suggest that SDF-1 alone is sufficient to induce cardiac repair. Most importantly, studies like those on the SDF-1:CXCR4 axis have suggested mechanisms critical for cardiac regenerative therapies that if clinical investigators continue to ignore will result in poorly designed studies that will continue to yield negative results. PMID- 22673498 TI - Sarcoplasmic reticulum and calcium cycling targeting by gene therapy. AB - Although progress in conventional treatments is making steady and incremental gains to reduce mortality associated with heart failure (HF), there remains a need to explore potentially new therapeutic approaches. HF induced by different etiologies such as coronary artery disease, hypertension, diabetes, infection or inflammation results generally in calcium cycling dysregulation at the myocyte level. Recent advances in understanding of the molecular basis of these calcium cycling abnormalities, together with the evolution of increasingly efficient gene transfer technology, has placed HF within the reach of gene-based therapy. Furthermore, the recent successful completion of a phase 2 trial targeting the sarcoplasmic reticulum calcium pump ushers in a new era for gene therapy for the treatment of HF. PMID- 22673497 TI - Gene- and cell-based bio-artificial pacemaker: what basic and translational lessons have we learned? AB - Normal rhythms originate in the sino-atrial node, a specialized cardiac tissue consisting of only a few thousands of nodal pacemaker cells. Malfunction of pacemaker cells due to diseases or aging leads to rhythm generation disorders (for example, bradycardias and sick-sinus syndrome (SSS)), which often necessitate the implantation of electronic pacemakers. Although effective, electronic devices are associated with such shortcomings as limited battery life, permanent implantation of leads, lead dislodging, the lack of autonomic responses and so on. Here, various gene- and cell-based approaches, with a particular emphasis placed on the use of pluripotent stem cells and the hyperpolarization activated cyclic nucleotide-gated-encoded pacemaker gene family, that have been pursued in the past decade to reconstruct bio-artificial pacemakers as alternatives will be discussed in relation to the basic biological insights and translational regenerative potential. PMID- 22673499 TI - GMP-adapted overexpression of CXCR4 in human mesenchymal stem cells for cardiac repair. AB - BACKGROUND: Human mesenchymal stem cells (MSC) have been utilized for cardiac regeneration after myocardial damage. Their clinical effects are marginal and only a minority of administered cells could make their way into the myocardium. The chemokine receptor CXCR4 has been identified as crucial for migration and homing of stem cells. In this study we overexpressed CXCR4 on human MSC to improve cell trafficking and tissue repair. METHODS: Human MSC were isolated from the spongiosa of tibia and femur as well as from pelvic bone marrow. MSC were characterized by differentiation assays and FACS analysis. CXCR4 was overexpressed by mRNA-nucleofection. Intracellular signaling was analyzed to demonstrate functionality of CXCR4. The modified Boyden chamber, wounding assays and time lapse microscopy were utilized to investigate MSC migration. RESULTS: MSC did not express relevant amounts of CXCR4 spontaneously. CXCR4 could be overexpressed in 93% of MSC with a cell viability of 62%. Functionality of the overexpressed CXCR4 was demonstrated by a significant cytosolic Ca(2+) increase and activation of different MAP kinases followed by SDF-1alpha stimulation. In contrast no improvement of cell migration could be observed. There was a strong basal MSC chemokinesis independent from CXCR4 expression. CONCLUSIONS: CXCR4 could be effectively overexpressed in human MSC by mRNA-nucleofection. Despite functionality of CXCR4 MSC were characterized by a strong basal chemokinesis that could not be further enhanced by CXCR4 overexpression. As isolation, culture and nucleofection of pelvic bone marrow-derived MSC basically fulfill the GMP requirements our approach seems suited for an in vivo application in patients. PMID- 22673500 TI - Achilles tendon of descending aorta: intimal tear distal to the left subclavian artery and anterograde dissection of descending aorta. PMID- 22673502 TI - Effect of metformin on hepatic glucose production in Japanese patients with type 2 diabetes mellitus. AB - We investigated the effect of metformin on hepatic glucose production and peripheral glucose uptake in Asian patients with type 2 diabetes mellitus. We recruited ten Japanese patients whose fasting glucose levels remained poorly controlled under meal-time injection of short-acting insulin. Metformin was added to their insulin therapy, and both hepatic glucose production and peripheral glucose uptake were assessed before and one week after metformin treatment, with the use of stable isotope [6,6-2H2] glucose. Metformin was titrated to a maximum dose of 500 mg. As a result, fasting glucose levels and hepatic glucose production were significantly improved after the metformin treatment (p < 0.01 and 0.02), whereas their peripheral glucose uptake was not significantly changed (p = 0.63). Furthermore, the change of fasting glucose levels was significantly correlated with that of hepatic glucose production, whose coefficient rho was 0.76 (p = 0.01). On the other hand, there was no significant correlation between the change of fasting glucose levels and that of peripheral glucose uptake (p = 0.43). In conclusion, low dose of metformin significantly reduced hepatic glucose production in Japanese patients with type 2 diabetes mellitus. The efficacy of metformin on correcting fasting hyperglycemia was strongly associated with reduced hepatic glucose production, rather than ameliorated peripheral glucose uptake. PMID- 22673503 TI - Mdm2 and MdmX partner to regulate p53. AB - Mdm2 regulates the stability, translation, subcellular localization and transcriptional activity of p53 protein. Mdm2-dependent p53 inhibition is essential in regulating p53 activity during embryonic development and in adult tissues. MdmX, an Mdm2 homolog, is also essential for p53 inhibition in vivo. Recent advances in the field from biochemical and genetic studies have revealed an essential role for the MdmX RING domain in Mdm2-dependent p53 polyubiquitination and degradation. Mdm2 on its own is a monoubiquitin E3 ligase for p53, but is converted to a p53 polyubiquitin E3 ligase by MdmX through their RING-RING domain interactions. MdmX acts as an activator as well as a substrate of Mdm2/MdmX E3 complex. The insufficiency of Mdm2 for p53 polyubiquitination also demands other p53 E3 ligases or E4 factors be incorporated into the p53 degradation arena. Deubiquitinases nullify the effects of E3 actions and reverse the ubiquitination process, which permits a diverse and dynamic pattern of p53 stability control. Unsurprisingly, stress signals target MdmX to disengage the p53/Mdm2 feedback loop for timely and appropriate p53 responses to these stresses. PMID- 22673506 TI - The murine Gcap14 gene encodes a novel microtubule binding and bundling protein. AB - Microtubules form flexible fibers, which are utilized in cell proliferation and differentiation. Although the flexibility of microtubules was shown to be regulated by various microtubule-associated proteins, this regulation is still far from complete understanding. Here, we report a new potential regulator of microtubules in mammals. Gcap14 colocalizes with microtubules in mammalian cells transfected with Gcap14 expression vector. Association of Gcap14 with microtubules was confirmed by biochemical subcellular fractionation. Recombinant Gcap14 protein cosedimented with pure microtubules, indicating a direct binding between the two. Furthermore, recombinant Gcap14 was shown to have the ability of inducing microtubule bundling in vitro. PMID- 22673505 TI - Tumor suppressor functions of FBW7 in cancer development and progression. AB - FBW7 (F-box and WD repeat domain-containing 7) has been characterized as an onco suppressor protein in human cancers. Recent studies have also shown that FBW7 exerts its anti-tumor function primarily by promoting the degradation of various oncoproteins, through which FBW7 regulates cellular proliferation, differentiation and causes genetic instability. In this review, we will discuss the role of FBW7 downstream substrates and how dysregulation of Fbw7-mediated proteolysis of these substrates contributes to tumorigenesis. Additionally, we will also summarize the currently available various Fbw7-knockout mouse models that support Fbw7 as a tumor suppressor gene in the development and progression of human malignancies. PMID- 22673504 TI - Pirh2 RING-finger E3 ubiquitin ligase: its role in tumorigenesis and cancer therapy. AB - The ubiquitin-dependent proteasome system plays a critical role in many cellular processes and pathogenesis of various human diseases, including cancer. Although there are a large number of E3 ubiquitin ligases, the majority are RING-finger type E3s. Pirh2, a target of p53 transcription factor, contains a highly conserved C(3)H(2)C(3) type RING domain. Importantly, Pirh2 was found to regulate a group of key factors dedicated to the DNA damage response, such as p53, p73, PolH, and c-Myc. Interestingly, Pirh2 was upregulated or downregulated in different types of cancers. These suggest that Pirh2 is implicated in either promoting or suppressing tumor progression in a tissue-dependent manner. This review will focus on the major findings in these studies and discuss the potential to explore Pirh2 as a cancer therapeutic target. PMID- 22673507 TI - THAP11, a novel binding protein of PCBP1, negatively regulates CD44 alternative splicing and cell invasion in a human hepatoma cell line. AB - THAP11 is an essential factor involved in ES cell pluripotency and cell growth. Here, we identified THAP11 as a novel physiological binding partner of PCBP1. In HepG2 cells, THAP11 overexpression inhibited CD44 v6 expression and cell invasion. However, when deleting the binding domain with PCBP1 or endogenous PCBP1 was knocked down, THAP11 failed to inhibit CD44 v6 expression, indicating that THAP11 regulates CD44 v6 expression through interacting with PCBP1. In HCC patients, the expression of THAP11 mRNA significantly correlated with PCBP1 mRNA expression. Our results suggest a novel role of THAP11 in CD44 alternative splicing and hepatoma invasion. PMID- 22673508 TI - Active site phosphoryl groups in the biphosphorylated phosphotransferase complex reveal dynamics in a millisecond time scale. AB - The N-terminal domain of Enzyme I (EIN) and phosphocarrier HPr can form a biphosphorylated complex when they are both phosphorylated by excess cellular phosphoenolpyruvate. Here we show that the electrostatic repulsion between the phosphoryl groups in the biphosphorylated complex results in characteristic dynamics at the active site in a millisecond time scale. The dynamics is localized to phospho-His15 and the stabilizing backbone amide groups of HPr, and does not impact on the phospho-His189 of EIN. The dynamics occurs with the k(ex) of ~500 s(-1) which compares to the phosphoryl transfer rate of ~850 s(-1) between EIN and HPr. The conformational dynamics in HPr may be important for its phosphotransfer reactions with multiple partner proteins. PMID- 22673509 TI - Extensions of PSD-95/discs large/ZO-1 (PDZ) domains influence lipid binding and membrane targeting of syntenin-1. AB - Syntenin-1 is a PDZ protein involved in receptor recycling and clustering. Its two PDZ domains interact with various receptors and phosphoinositides, and are flanked by N- and C-terminal regions. Here, we report the identification of an autoinhibitory peptide stretch in the N-terminus that might be regulated by phosphorylation. We further establish that basic residues in the C-terminal region mediate electrostatic interactions with reconstituted liposomes and contribute to the plasma membrane targeting. Our study adds new components to the multi-dentate membrane targeting mechanism and highlights the role of N- and C terminal PDZ extensions in the regulation of syntenin-1 plasma membrane localization. PMID- 22673510 TI - Spatiotemporal resolution of Ca2+ signaling events by real time imaging of single B cells. AB - Antigen-induced B cell activation requires mobilization of the Ca(2+) second messenger. This process is associated with the subcellular relocalization of signal effector proteins of the B cell antigen receptor such as the adaptor protein SLP65. Here we describe a broadly applicable live cell imaging method to simultaneously visualize intracellular Ca(2+) flux profiles and the translocation of cytosolic signaling proteins to the plasma membrane in real time. Our approach delineated the kinetic hierarchy of Ca(2+) signaling events in B cells and revealed a timely ordered contribution of various organelles to the overall Ca(2+) signal. The developed experimental setup provides a useful tool to resolve the spatiotemporal signaling dynamics in various receptor signaling systems. PMID- 22673511 TI - Inhibition of bacterial adhesion to live human cells: activity and cytotoxicity of synthetic mannosides. AB - Bacterial adhesion to glycosylated surfaces is a key issue in human health and disease. Inhibition of bacterial adhesion by suitable carbohydrates could lead to an anti-adhesion therapy as a novel approach against bacterial infections. A selection of five alpha-mannosides has been evaluated as inhibitors of bacterial adhesion to the polysaccharide mannan, as well as to the surface of live human HT 29 cells. Cell toxicity studies were performed to identify the therapeutic window for a potential in vivo-application of the tested carbohydrates. A previously published mannosidic squaric acid diamide was shown to be exceptionally effective as inhibitor of the bacterial lectin FimH. PMID- 22673512 TI - alpha-Actinin4 nuclear translocation mediates gonadotropin-releasing hormone stimulation of follicle-stimulating hormone beta-subunit gene transcription in LbetaT2 cells. AB - Gonadotropin-releasing hormone (GnRH) regulates the synthesis and secretion of follicle-stimulating hormone (FSH) by stimulating the transcription of Fshbeta gene. Our iTRAQ quantitative proteomics result showed that the abundance of alpha actinin4 (ACTN4) increased in the nuclei of LbetaT2 cells upon GnRH induction. Using RNA interference, reverse transcription and real-time PCR, luciferase and transient transfection assays, we proved that ACTN4 is involved in the regulation of mouse Fshbeta gene (mFshbeta) transcription and its C-terminal calmodulin (CaM)-like domain is crucial for this process. Our study suggests that ACTN4 nuclear translocation mediates GnRH stimulation of mFshbeta gene transcription. PMID- 22673513 TI - MiR-26 controls LXR-dependent cholesterol efflux by targeting ABCA1 and ARL7. AB - Cellular cholesterol levels are tightly regulated and represent a balance of cholesterol uptake, endogenous synthesis and efflux. Although the classic transcriptional regulations of cholesterol metabolism by liver X receptors (LXRs) have been well studied, the potential effects of LXR-responsive microRNAs (miRNAs) still need to be unveiled. Here, we describe that miR-26, an LXR suppressed miRNA, inhibits the expression of the ATP-binding cassette transporter A1 (ABCA1) and ADP-ribosylation factor-like 7 (ARL7), two LXR target genes which play critical roles in cholesterol efflux. These findings have not only figured out an alternative mechanism for LXR regulation, but also provided a potential therapeutic target for cholesterol metabolic disorders. PMID- 22673514 TI - CRSBP-1/LYVE-1 ligands stimulate contraction of the CRSBP-1-associated ER network in lymphatic endothelial cells. AB - CRSBP-l/LYVE-1 ligands (PDGF-BB, VEGF-A(165) and hyaluronic acid) have been shown to induce opening of lymphatic intercellular junctions in vitro and in vivo by stimulating contraction of lymphatic endothelial cells (LECs). The mechanism by which CRSBP-1 ligands stimulate contraction of LECs is not understood. Here we demonstrate that CRSBP-1 is localized to the plasma membrane as well as intracellular fibrillar structures in LECs, including primary human dermal LECs and SVEC4-10 cells. CRSBP-1-associated fibrillar structures are identical to the ER network as evidenced by the co-localization of CRSBP-1 and BiP in these cells. CRSBP-1 ligands stimulate contraction of the ER network in a CRSBP-1-dependent and paclitaxel (a microtubule-stabilizing agent)-sensitive manner. These results suggest that ligand-stimulated ER contraction is associated with ligand stimulated contraction in LECs. PMID- 22673515 TI - Galactinol synthase across evolutionary diverse taxa: functional preference for higher plants? AB - Galactinol synthase (GolS), a GT8 family glycosyltransferase, synthesizes galactinol and raffinose series of oligosaccharides (RFOs). Identification and analysis of conserved domains in GTs among evolutionarily diverse taxa, structure prediction by homology modeling and determination of substrate binding pocket followed by phylogenetic analysis of GolS sequences establish presence of functional GolS predominantly in higher plants, fungi having the closest possible ancestral sequences. Evolutionary preference for a functional GolS expression in higher plants might have arisen in response to the need for galactinol and RFO synthesis to combat abiotic stress, in contrast to other organisms lacking functional GolS for such functions. PMID- 22673516 TI - Nemo-like kinase promotes etoposide-induced apoptosis of male germ cell-derived GC-1 cells in vitro. AB - Spermatogenesis is an extremely intricate process that is tightly regulated and orchestrated by a series of well-coordinated gene expression programmes. Nemo like kinase (NLK) is an evolutionarily conserved serine/threonine kinase that functions in a wide variety of developmental events. Nevertheless, the function of NLK in spermatogenesis has not been investigated. In this study, we found that the distribution of NLK in mice exhibited a dynamic change during testicular development and gradually became concentrated in the acrosomes of elongated spermatids. NLK overexpression promoted etoposide-induced apoptosis of male germ cell-derived GC-1 cells, while knockdown of NLK by RNA interference (RNAi) attenuated etoposide-induced apoptosis. Our findings suggest that NLK plays an important role in etoposide-induced germ cell apoptosis and may be associated with spermatogenesis. PMID- 22673517 TI - Suppression of cellular invasion by glybenclamide through inhibited secretion of platelet-derived growth factor in ovarian clear cell carcinoma ES-2 cells. AB - It has been demonstrated that potassium channels (K(+) channels) play significant roles in some malignant phenotypes. Here, we provide the first evidence that treatment with glybenclamide, an ATP-sensitive K(+) channel blocker, inhibited cell migration in an ovarian clear cell carcinoma cell line, ES-2. Treatment with glybenclamide or knockdown by siRNA targeted against K(+) channel subunits demonstrated the suppression of ovarian cancer cell invasion, which occurred via inhibition of PDGF-AA secretion. Therefore, our findings suggest that K(+) channel blockers may be useful chemotherapeutic drugs for blocking the invasiveness of ovarian cancers. PMID- 22673518 TI - Knockdown of von Hippel-Lindau protein decreases lung cancer cell proliferation and colonization. AB - Although von Hippel-Lindau protein (pVHL) is known as a tumor suppressor in kidney and other organs, it remains unclear whether pVHL plays a role in lung cancer development. We investigated the role of pVHL in lung cancer cell proliferation, migration, and colonization using stable A549 cells with knockdown of pVHL. We found that knockdown of pVHL promotes epithelial-mesenchymal transition (EMT) in lung cancer cells. Knockdown of pVHL decreased tumor colonization in a tail-vein injection model and decreased cell proliferation, whereas overexpression of constitutive active HIF increased tumor colonization, suggesting a HIF-independent function of pVHL in lung. Knockdown of pVHL decreased phosphorylation of FAK and expression of integrin, suggesting that pVHL regulates lung cancer development via integrin/FAK signaling pathway. PMID- 22673520 TI - Constitutively active Cullin-RING-Ligases fail to rescue loss of NEDD8 conjugation in Schizosaccharomyces pombe. AB - In fission yeast, the only known essential function of Ned8p is the modification of the cullin, Pcu1p, and subsequent Cullin-RING-Ligase (CRL) activation and substrate ubiquitination. We show here that a functional Pcu1p mutant, deleted for its C-terminal autoinhibitory domain, which negates the requirement of neddylation for ligase activity, is unable to rescue the loss of neddylation. These findings suggest that the neddylation of non-cullin substrate(s) are required for Schizosaccharomyces pombe viability. PMID- 22673519 TI - Leucine-rich repeat, immunoglobulin-like and transmembrane domain 3 (LRIT3) is a modulator of FGFR1. AB - Fibroblast growth factor receptors (FGFRs) play critical roles in craniofacial and skeletal development via multiple signaling pathways including MAPK, PI3K/AKT, and PLC-?. FGFR-mediated signaling is modulated by several regulators. Proteins with leucine-rich repeat (LRR) and/or immunoglobulin (IG) superfamily domains have been suggested to interact with FGFRs. In addition, fibronectin leucine-rich repeat transmembrane protein 3 (FLRT3) has been shown to modulate the FGFR-mediated signaling via the fibronectin type III (FNIII) domain. Therefore proteins with LRR, IG, and FNIII are candidate regulators of the FGFRs. Here we identify leucine-rich repeat, immunoglobulin-like and transmembrane domain 3 (LRIT3) as a regulator of the FGFRs. PMID- 22673521 TI - LidNA, a novel miRNA inhibitor constructed with unmodified DNA. AB - Many miRNA inhibitors have been developed and they are chemically modified oligonucleotides such as 2?-O-methylated RNA and locked nucleic acid (LNA). Unmodified DNA was not yet reported as a miRNA inhibitor because of the low affinity of DNA/miRNA compared to mRNA/miRNA. We designed a structured unmodified DNA that significantly inhibits miRNA function. The clue structure for activity is the miRNA binding site between double stranded regions which is responsible for the miRNA inhibitory activity and tight binding to miRNA. We developed the miRNA inhibitor constructed with unmodified DNA, and named it LidNA, DNA that puts a lid on miRNA function. PMID- 22673522 TI - Calmodulin regulates the translocation of Grb7 into the nucleus. AB - We describe in this report the presence of a nuclear localization signal (NLS) overlapping the calmodulin-binding domain (CaM-BD) of the growth factor receptor bound protein 7 (Grb7). We show that deletion of the CaM-BD of Grb7 prevents its nuclear localization, and that its Src homology 2 (SH2) domain might participate as well in the translocation process. Also, treating cells with the CaM antagonist N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) enhances the presence of Grb7 in the nucleus. We propose that CaM inhibits the translocation of Grb7 to the nucleus after binding to its CaM-BD and therefore occluding its overlapping NLS. PMID- 22673523 TI - LPS-induced chemokine expression in both MyD88-dependent and -independent manners is regulated by Cot/Tpl2-ERK axis in macrophages. AB - LPS signaling is mediated through MyD88-dependent and -independent pathways, activating NF-?B, MAP kinases and IRF3. Cot/Tpl2 is an essential upstream kinase in LPS-mediated activation of ERKs. Here we explore the roles of MyD88 and Cot/Tpl2 in LPS-induced chemokine expression by studying myd88(-/-) and cot/tpl2( /-) macrophages. Among the nine LPS-responsive chemokines examined, mRNA induction of ccl5, cxcl10, and cxcl13 is mediated through the MyD88-independent pathway. Notably, Cot/Tpl2-ERK signaling axis exerts negative effects on the expression of these three chemokines. In contrast, LPS-induced gene expression of ccl2, ccl7, cxcl2, cxcl3, ccl8, and cxcl9 is mediated in the MyD88-dependent manner. The Cot/Tpl2-ERK axis promotes the expression of the first four and inhibits the expression of the latter two. Thus, LPS induces expression of multiple chemokines through various signaling pathways in macrophages. PMID- 22673524 TI - Short-chain fatty acid receptor GPR41-mediated activation of sympathetic neurons involves synapsin 2b phosphorylation. AB - Synapsins are neuronal phosphoproteins that coat synaptic vesicles and are believed to function in the regulation of neurotransmitter release. The signaling mechanism for short-chain free fatty acid (SCFA)-stimulated NE release was examined using primary-cultured mouse sympathetic cervical ganglion neurons. Pharmacological and knockdown experiments showed that activation of sympathetic neurons by SCFA propionate involves SCFA receptor GPR41 linking to G??-PLC?3 ERK1/2-synapsin 2 signaling. Further, synapsin 2b directly interacts with activated ERK1/2 and can be phosphorylated on serine when SCFA activates sympathetic neurons. PMID- 22673525 TI - Regulation of lipid biosynthesis by phosphatidylinositol-specific phospholipase C through the transcriptional repression of upstream activating sequence inositol containing genes. AB - The regulation of phospholipid biosynthesis in Saccharomyces cerevisiae through cis-acting upstream activating sequence inositol (UAS(ino)) and trans-acting elements, such as the INO2-INO4 complex and OPI1 by inositol supplementation in growth is thoroughly studied. In this study, we provide evidence for the regulation of lipid biosynthesis by phosphatidylinositol-specific phospholipase C (PLC) through UAS(ino) and the trans-acting elements. Gene expression analysis and radiolabelling experiments demonstrated that the overexpression of rice PLC in yeast cells altered phospholipid biosynthesis at the levels of transcriptional and enzyme activity. This is the first report implicating PLC in the direct regulation of lipid biosynthesis. PMID- 22673526 TI - Platelet storage and flow cytometry, an interesting couple. PMID- 22673527 TI - Neonatal neuroblastoma. AB - Neuroblastoma, an embryonal tumour arising from the sympathetic nervous system, is the most common neonatal malignancy accounting for >20% of neonatal cancers. It may present as an antenatal adrenal mass or more commonly with localised or metastatic (4s/Ms) disease, which is usually low risk with a very good clinical outcome. Around 20% of neonatal neuroblastoma presents with spinal cord compression requiring prompt diagnosis and treatment with steroids and chemotherapy to relieve the cord compression. Patients with stage Ms disease without life- or organ-threatening symptoms or adverse genetic features (MYCN amplification or segmental chromosomal abnormalities) can be safely observed for spontaneous regression which may also occur with other localised neonatal neuroblastomas. Universal mass screening for neuroblastoma is not indicated but targeted screening of infants at risk of hereditary neuroblastoma with germline ALK or PHOX2B mutations is appropriate. Future studies will be aimed at observing more patients without adverse genetics or life-threatening features. PMID- 22673528 TI - Spin crossover in phosphorus- and arsenic-bridged cyclopentadienyl-manganese(II) dimers. AB - Manganocene reacts with LiE(SiMe(3))(2) (E = P or As) to give [(eta(5)-Cp)Mn{MU E(SiMe(3))(2)}](2), where E = P (1) or As (2). The temperature dependence of the magnetic susceptibility in 1 and 2 is due to antiferromagnetic exchange and to spin-crossover (SCO). Compound 2 shows two-step SCO with hysteresis, involving high-spin (S = 5/2) and intermediate-spin S = (3/2) Mn(II). PMID- 22673529 TI - Therapeutic potential of transplanted placental mesenchymal stem cells in treating Chinese miniature pigs with acute liver failure. AB - BACKGROUND: Stem cell-based therapy to treat liver diseases is a focus of current research worldwide. So far, most such studies depend on rodent hepatic failure models. The purpose of this study was to isolate mesenchymal stem cells from human placenta (hPMSCs) and determine their therapeutic potential for treating Chinese experimental miniature pigs with acute liver failure (ALF). METHODS: hPMSCs were isolated and analyzed for their purity and differentiation potential before being employed as the donor cells for transplantation. ALF models of Chinese experimental miniature pigs were established and divided into four groups: no cell transplantation; hPMSCs transplantation via the jugular vein; X ray-treated hPMSCs transplantation via the portal vein; and hPMSCs transplantation via the portal vein. The restoration of biological functions of the livers receiving transplantation was assessed via a variety of approaches such as mortality rate determination, serum biochemical analysis, and histological, immunohistochemical, and genetic analysis. RESULTS: hPMSCs expressed high levels of CD29, CD73, CD13, and CD90, had adipogenic, osteogenic, and hepatic differentiation potential. They improved liver functions in vivo after transplantation into the D-galactosamine-injured pig livers as evidenced by the fact that ALT, AST, ALP, CHE, TBIL, and TBA concentrations returned to normal levels in recipient ALF pigs. Meanwhile, histological data revealed that transplantation of hPMSCs via the portal vein reduced liver inflammation, decreased hepatic denaturation and necrosis, and promoted liver regeneration. These ameliorations were not found in the other three groups. The result of 7-day survival rates suggested that hPMSCs transplantation via the portal vein was able to significantly prolong the survival of ALF pigs compared with the other three groups. Histochemistry and RT-PCR results confirmed the presence of transplanted human cells in recipient pig livers (Groups III, IV). CONCLUSIONS: Our data revealed that hPMSCs could not only differentiate into hepatocyte-like cells in vitro and in vivo, but could also prolong the survival time of ALF pigs. Regarding the transplantation pathways, the left branch of the portal vein inside the liver was superior to the jugular vein pathway. Thus, hPMSCs transplantation through the portal vein by B-ultrasonography may represent a superior approach for treating liver diseases. PMID- 22673530 TI - Immunohistochemical expression of Wilms' tumor protein (WT1) in developing human epithelial and mesenchymal tissues. AB - The Wilms' tumor (WT1) gene and its protein product are known to exhibit a dynamic expression profile during development and in the adult organism. Apart from a nuclear expression observed in the urogenital system, its precise localization in other developing human tissues is still largely unknown. Accordingly, the aim of this study was to investigate immunohistochemically the temporal and spatial distribution of WT1 in epithelial and mesenchymal developing human tissues from gestational weeks 7-24. For this purpose we used antibodies against the N-terminal of WT1. As might be expected, WT1 nuclear expression was observed in mesonephric/metanephric glomeruli, metanephric blastema, celom derived membranes (pleura, peritoneum, serosal surfaces) and sex cords. With regard to mesenchymal tissues, a similar nuclear staining was also obtained in the mesenchyme surrounding Mullerian and Wolffian ducts, as well as in the submesothelial mesenchymal cells of all celomatic-derived membranes. The most striking finding was the detection of strong WT1 cytoplasmic immunostaining in developing skeletal and cardiac muscle cells and endothelial cells. The tissue specific expression of WT1, together with its different nuclear/cytoplasmic localization, both suggest that WT1 protein may have shuttling properties, acting as a protein with complex regulator activity in transcriptional/translation processes during human ontogenesis. The reported cytoplasmic expression of WT1 in human rhabdomyosarcomas and in many vascular tumors strongly suggests an oncofetal expression of this protein. Although not specific, WT1 cytoplasmic expression can be used as a marker of skeletal muscle and endothelial differentiation in an appropriate morphological context. PMID- 22673531 TI - Serum long-chain n-3 polyunsaturated fatty acids, methylmercury and blood pressure in an older population. AB - Fish or fish oil consumption has been associated with lower blood pressure. Fish may also contain methylmercury, which has been associated with cardiovascular diseases and higher blood pressure. Our aim was to study the associations of serum long-chain n-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA), mainly reflecting fish or fish oil intake, and hair mercury concentration with blood pressure. Data were available for 848 men and 909 women from the Kuopio Ischaemic Heart Disease Risk Factor Study, aged 53-73 years. We excluded participants with ischemic heart disease, stroke, diabetes or hypertension treatment, leaving 396 men and 372 women. Log-transformed values were used to study the associations. The mean serum concentrations were 1.63% (s.d. 0.91) for EPA, 0.77% (s.d. 0.16) for DPA and 2.73% (s.d. 0.90) for DHA of all serum fatty acids. Multivariate adjusted serum EPA+DPA+DHA was associated with lower systolic blood pressure (beta = -4.50, 95% confidence interval (CI) -8.02 - -0.99) and pulse pressure (beta = -4.41, 95% CI -6.95 - -1.87), but not with diastolic blood pressure (beta = -0.45, 95% CI -2.31-1.52). The associations were similar with EPA, DPA and DHA evaluated individually. The mean hair mercury concentration was 1.42 MUg g(-1) (s.d. 1.54). Hair mercury was not associated with blood pressure and it did not modify the association between PUFA and blood pressure. These results suggest that higher serum long-chain n-3 PUFA concentration has a modest inverse association with blood pressure in older men and women. PMID- 22673532 TI - Investigation of iodine deficient state and iodine supplementation in patients with severe motor and intellectual disabilities on long-term total enteral nutrition. AB - Iodine concentrations of enteral nutrition (EN) formulae available in Japan are very low and long-term total EN (TEN) might result in hypothyroidism due to iodine deficiency (HID). Our aim of this study was to determine the degree of iodine deficiency (ID) and need for iodine supplementation (IS) in patients with severe motor and intellectual disabilities (SMID) on long-term TEN. Thyroid function including urinary iodine concentration (UIC) was monitored, and powdered kelp was provided as a source of iodine supplement. Thirty-five SMID on TEN participated in our study. UIC less than 100 MUg /L, representing ID, were detected in 97 % of them. Their TSH ranged from 0.5 to 90 MUIU/mL. IS using powdered kelp raised their UIC to the normal range. Thyroid function also recovered in the five hypothyroidism cases, which were diagnosed as HID, was also detected. In Japan, there must be many cases with ID associated with long term TEN. We also discuss the regulation of thyroid function in the iodine deficient state. PMID- 22673533 TI - Low serum free testosterone level is associated with carotid intima-media thickness in middle-aged Japanese men. AB - In the present study, we measured carotid artery intima-media thickness (CIMT) and assessed several metabolic factors in middle-aged healthy Japanese men to clarify the relation between testosterone and atherosclerosis. The study comprised 176 male employees aged >=40 years who visited Osaka University Healthcare Center for their annual health examinations. Serum total testosterone (TT) concentration was measured using radioimmunoassay (RIA) and serum free testosterone concentration was measured using analog ligand RIA (aFT). A multivariate model adjusted for age, body mass index, mean arterial pressure and treatment for hypertension demonstrated a significant association between aFT and CIMT. Even after adjustment for other clinically relevant factors, the significant association between aFT and CIMT was not attenuated. After adjustment for all other clinically relevant factors, both univariate and multivariate models ascertained the stepwise association that a level of aFT of <=10.0 pg/mL was significantly associated with CIMT. However, the association between TT and CIMT was not significant in either univariate or multivariate models. We conclude that our finding showing that low serum aFT level is an influencing and independent risk factor for CIMT is of value in the clinical setting because no other studies, to our knowledge, have conducted multivariate analyses using the various metabolic factors included in the present analyses. PMID- 22673534 TI - Prognostic value of poorly differentiated carcinoma in Japanese Society of Thyroid Surgery in a series of papillary thyroid carcinoma patients: comparison with risk classification system in Kuma Hospital. AB - Papillary thyroid carcinoma (PTC) often has poorly differentiated components, and it is discriminated from others and classified as an independent entity in the General Rules for the Description of Thyroid Cancer by Japanese Society of Thyroid Surgery (JSTS). In this study, we compared the prognostic significance between this type of poorly differentiated carcinoma (PDC-JSTS) and our risk classification system based on pre- and intraoperative findings in a series of PTC patients. The 10-year lymph node- and distant organ recurrence-free survival (LN-DFS and DRFS) and cause-specific survival (CSS) of high-risk patients were much poorer than in PDC-JSTS patients. In multivariate analysis, PDC-JSTS independently predicted a poor prognosis, but prognostic impacts for LN-DFS, DRFS, and CSS of high-risk in our risk classification were stronger than those of PDC-JSTS. In conclusion, it is appropriate that PDC-JSTS is defined as a subtype of PTC rather than as an independent entity. PMID- 22673535 TI - A risk/tolerance approach to the preparticipation examination. PMID- 22673536 TI - Hockey-related emergency department visits after a change in minor hockey age groups. AB - OBJECTIVE: To examine ice hockey injury rates presenting to emergency departments (EDs) in 2 separate cohorts of players before and after a policy change for age groups in minor hockey. DESIGN: : Retrospective cross-sectional study. SETTING: Retrospective review of ice hockey injuries presenting to 2 tertiary care and 5 community care EDs in Edmonton, Alberta. PATIENTS: Two cohorts of minor ice hockey players were constructed. The pre-age change cohort consisted of 4215 registered male hockey players. The post-age change cohort consisted of 3811 registered male hockey players. ASSESSMENT OF RISK FACTORS: The risk of fracture, head and neck injury (intracranial and nonintracranial), and all other injuries presenting to EDs were compared between the pre-age change and post-age change cohorts. MAIN OUTCOME MEASURES: Presentation to an ED with an injury occurring in ice hockey between September 1 and April 31 for the years 1997 through 2010. RESULTS: Overall, significantly lower injury rates were observed in the post-age change cohort for players in the Peewee division; however, no significant differences were observed for the rate of fractures, and intracranial or nonintracranial head and neck injuries. There were no statistically significant differences observed between the pre-age change and post-age change cohorts in the Atom or Bantam divisions. CONCLUSIONS: Introducing body checking 1 year earlier than in a previous cohort (11 vs 12 years of age) neither significantly decreased nor increased the rate of serious ice hockey injuries occurring 2 years after the introduction of body checking. Further research is recommended to evaluate the claim that introducing body checking lowers injury rates in older divisions of hockey. PMID- 22673537 TI - Association between postexercise hypotension and long-term training-induced blood pressure reduction: a pilot study. AB - OBJECTIVE: The interindividual variability in the efficacy of regular endurance exercise to lower blood pressure is high. Therefore, to optimize training prescriptions, predictors would be desirable. The main hypothesis of the present study was an association between postexercise hypotension after an exhaustive exercise test and chronic blood pressure reductions in response to an endurance training program. DESIGN: Uncontrolled prospective training study. SETTING: University department. PARTICIPANTS: Healthy untrained subjects were recruited by flyers. Inclusion criteria were age 30 to 60 years, body mass index 25 to 35 kg/m(2), untrained status (<1 hour/week regular activity; V[Combining Dot Above]O(2max) < 45 mL.min(-1).kg(-1)), blood pressure 150/95 mm Hg, nonsmoker; 14 subjects were included, 12 could be analyzed. INTERVENTION: Walking/running 4 times per week at 60% heart rate reserve for 4 weeks. MAIN OUTCOME MEASURES: Difference in blood pressure from the initial resting value to 1 and 24 hours after the initial test (acute) and the resting value before the final test (chronic), respectively. RESULTS: Initial resting systolic blood pressure was 134 +/- 18 mm Hg. Values were significantly reduced at all time points thereafter (1 hour: 125 +/- 13 mm Hg; 24 hours: 128 +/- 12 mm Hg; final: 125 +/- 18 mm Hg). Acute and chronic changes correlated significantly (1 hour: P = 0.003; r = 0.77; 24 hours: P = 0.017; r = 0.67). Results for diastolic blood pressure were comparable yet less pronounced. CONCLUSIONS: The magnitude of postexercise hypotension is a promising candidate for the prediction of individual blood pressure-related training efficacy. Easily determined, it might be used to improve training prescriptions. However, further studies are needed to assess predictive accuracy. PMID- 22673538 TI - Bilateral knee pain in a high-level gymnast. AB - Gymnast wrist or distal radial physeal injury is a common entity among gymnasts of all levels. It can lead to chronic pain, inability to perform, and growth issues at the wrist for these young athletes. However, less has been reported about other overuse stress injuries in this group. We present the case of a prepubescent female gymnast complaining of chronic bilateral knee pain. She was found to have bilateral distal femoral physeal stress injuries and had a similar clinical course to any gymnast diagnosed with the same injury at the wrist. PMID- 22673539 TI - Expression of Ki67, BCL-2, and COX-2 in canine cutaneous mast cell tumors: association with grading and prognosis. AB - The expression of Ki67, BCL-2, and COX-2 was investigated in 53 canine cutaneous mast cell tumors (MCTs) by immunohistochemistry and quantitative real time polymerase chain reaction (qPCR) to evaluate their prognostic significance and the association with the histologic grading and the mitotic index (MI). MCTs were graded according to the Patnaik grading system and the novel 2-tier grading system proposed by Kiupel. The numbers of mitotic figures/10 high-power fields (MI) were counted. Both grading systems were significantly associated with prognosis. The Patnaik grading was of limited prognostic value for grade 2 MCTs, with 23% being associated with mortality. The concordance among pathologists was strongly improved by the application of the 2-tier grading system, and 71% of high-grade MCTs were associated with a high mortality rate. MI and Ki67 protein expression were significantly associated with grading and survival. No significant association between BCL-2 protein expression and either grading system or health status was observed. BCL-2 mRNA expression was significantly higher in grade 2 than in grade 1 MCTs, while no statistically significant differences were detected between low- and high-grade MCTs. The increased BCL-2 mRNA level was significantly associated with increased mortality rate. The COX-2 protein expression was detected in 78% of the MCTs investigated. However, neither association with the tumor grade nor with the health status was observed. COX-2 mRNA was significantly up-regulated in MCTs compared to surgical margins and control skin tissue, but it was neither associated with tumor grade nor with survival. PMID- 22673540 TI - Removal of organic toxic chemicals using the spent mushroom compost of Ganoderma lucidum. AB - The removal of the organic toxic chemicals di-n-butyl phthalate (DBP), di-2-ethyl hexyl phthalate (DEHP), nonylphenol (NP), and bisphenol-A (BPA) by laccase obtained from the spent mushroom compost (SMC) of the white rot fungi, Ganoderma lucidum, was investigated. The optimal conditions for the extraction of laccase from SMC required using sodium acetate buffer (pH 5.0, solid : solution ratio 1 : 5), and extraction over 3 h at 4 degrees C. The removal of NP was enhanced by adding CuSO(4) (1 mM), MnSO(4) (0.5 mM), tartaric acid (20 mM), 2,2'-azino-bis-(3 ethylbenzothiazoline-6-sulfonic acid) (ABTS; 1 mM), and 1-hydroxybenzotriazole (HBT; 20 mg L(-1)), with ABTS yielding a higher NP removal efficiency than the other additives. At a concentration of 2 mg L(-1), DBP, DEHP, NP, and BPA were almost entirely removed by laccase after incubation for 1 day. The removal efficiencies, in descending order of magnitude, were DBP > BPA > NP > DEHP. We believe that these findings could provide useful information for improving the efficiency of the removal of organic toxic chemicals in the environment. PMID- 22673541 TI - A statistical modeling approach for evaluating auto-segmentation methods for image-guided radiotherapy. AB - We proposed a statistical modeling method for the quantitative evaluation of segmentation methods used in image guided radiotherapy. A statistical model parameterized on a Beta distribution was built upon the observations of the volume overlap between the segmented structure and the referenced structure. A statistical performance profile (SPP) was then estimated from the model using the generalized maximum likelihood approach. The SPP defines the probability density function characterizing the distribution of performance values and provides a graphical visualization of the segmentation performance. Different segmentation approaches may be influenced by image quality or observer variability. Our statistical model was able to quantify the impact of these variations and displays the underlying statistical performance of the segmentation algorithm. We demonstrated the efficacy of this statistical model using both simulated data and clinical evaluation studies in head and neck radiotherapy. Furthermore, the resulting SPP facilitates the measurement of the correlation between quantitative metrics and clinical experts' decision, and ultimately is able to guide the clinicians in selecting segmentation methods for radiotherapy. PMID- 22673543 TI - A 66-year-old man with prostate-specific antigen recurrence and lung mass after radical prostatectomy. PMID- 22673542 TI - Inhibition of Src kinase activity attenuates amyloid associated microgliosis in a murine model of Alzheimer's disease. AB - BACKGROUND: Microglial activation is an important histologic characteristic of the pathology of Alzheimer's disease (AD). One hypothesis is that amyloid beta (Abeta) peptide serves as a specific stimulus for tyrosine kinase-based microglial activation leading to pro-inflammatory changes that contribute to disease. Therefore, inhibiting Abeta stimulation of microglia may prove to be an important therapeutic strategy for AD. METHODS: Primary murine microglia cultures and the murine microglia cell line, BV2, were used for stimulation with fibrillar Abeta1-42. The non-receptor tyrosine kinase inhibitor, dasatinib, was used to treat the cells to determine whether Src family kinase activity was required for the Abeta stimulated signaling response and subsequent increase in TNFalpha secretion using Western blot analysis and enzyme-linked immunosorbent assay (ELISA), respectively. A histologic longitudinal analysis was performed using an AD transgenic mouse model, APP/PS1, to determine an age at which microglial protein tyrosine kinase levels increased in order to administer dasatinib via mini osmotic pump diffusion. Effects of dasatinib administration on microglial and astroglial activation, protein phosphotyrosine levels, active Src kinase levels, Abeta plaque deposition, and spatial working memory were assessed via immunohistochemistry, Western blot, and T maze analysis. RESULTS: Abeta fibrils stimulated primary murine microglia via a tyrosine kinase pathway involving Src kinase that was attenuated by dasatinib. Dasatinib administration to APP/PS1 mice decreased protein phosphotyrosine, active Src, reactive microglia, and TNFalpha levels in the hippocampus and temporal cortex. The drug had no effect on GFAP levels, Abeta plaque load, or the related tyrosine kinase, Lyn. These anti inflammatory changes correlated with improved performance on the T maze test in dasatinib infused animals compared to control animals. CONCLUSIONS: These data suggest that amyloid dependent microgliosis may be Src kinase dependent in vitro and in vivo. This study defines a role for Src kinase in the microgliosis characteristic of diseased brains and suggests that particular tyrosine kinase inhibition may be a valid anti-inflammatory approach to disease. Dasatinib is an FDA-approved drug for treating chronic myeloid leukemia cancer with a reported ability to cross the blood-brain barrier. Therefore, this suggests a novel use for this drug as well as similar acting molecules. PMID- 22673544 TI - Ureteral ectopia inserting into ipsilateral epididymis resulting in inflammatory paratesticular tumor. AB - An 8-year-old male with a history of VACTERL association was found to have a paratesticular mass. The patient was treated successfully with a radical orchiectomy and found to have ureteral ectopia inserting into the ipsilateral epididymis, resulting in this paratesticular mass caused by inflammation of the epididymis. This is the only reported case in the English literature of an ectopic ureter inserting into the epididymis and presenting as a paratesticular tumor. In unclear cases of paratesticular, inflammatory appearing masses, inguinal exploration is warranted. PMID- 22673545 TI - Nephrogenic adenoma in a urethral diverticulum. AB - Nephrogenic adenoma (NA) is a rare benign metaplastic lesion of the urothelial tract that arises as a response to injury and chronic inflammation. Although the most common site for NA is the bladder, it can occur in any part of urinary tract lined by urothelium. NA can mimic minor variants of urothelial cancer, clear cell adenocarcinoma, and prostate adenocarcinoma, making a combination of histologic examination and immunohistochemistry essential for diagnosis. We hereby report a rare case of nephrogenic adenoma arising in a urethral diverticulum. PMID- 22673546 TI - Comparison of retrograde intrarenal surgery and mini-percutaneous nephrolithotomy in children with moderate-size kidney stones: results of multi-institutional analysis. AB - OBJECTIVE: To compare the outcomes of miniaturized percutaneous nephrolithotomy (mini-perc) and retrograde intrarenal surgery (RIRS) in children for 10- to 30-mm renal calculi by evaluating operative data, stone-free rates, and associated complications. METHODS: The records of 201 pediatric patients who underwent mini perc (n = 106) or RIRS (n = 95) for intrarenal stones of 10- to 30-mm size were reviewed retrospectively. The chi(2) test was applied to compare the success rates, postoperative complications, and blood transfusion rates, and the Mann Whitney U test was used to compare the means of hospital stay, fluoroscopy, and operative time for mini-perc and RIRS. RESULTS: The stone-free rate was 84.2% for the RIRS group and 85.8% for the mini-perc group after a single procedure (P = .745). These percentages increased to 92.6% and 94.3% with adjunctive therapies for RIRS and mini-perc, respectively. Minor complications classified as Clavien I or II occurred in 17% and 8.4% in mini-perc and RIRS, respectively. No major complications (Clavien III-V) occurred in either group. Overall complication rates in mini-perc were higher, but the differences were not statistically significant (P = .07). However, 7 patients in the mini-perc group received blood transfusions, whereas none of the children in the RIRS group were transfused (P = .015). The mean hospital stay, fluoroscopy, and operation times were significantly longer in the mini-perc group. CONCLUSION: This study demonstrates that RIRS is an effective alternative to mini-perc in pediatric patients with intermediate-sized renal stones. Operative time, radiation exposure, hospital stay, and morbidities of percutaneous nephrolithotomy (PNL) can be significantly reduced with the RIRS technique. PMID- 22673547 TI - Transaortic approach to residual ventricular septal shunt after repairing corrected transposition of the great arteries. AB - Many surgical approaches have been taken when closing ventricular septal defects after correcting transposition of the great arteries in order to avoid postoperative complete heart block. We describe a residual ventricular septal shunt that developed after repair using de Leval's method in a patient with congestive heart failure. The defect was closed transaortically without a complete heart block. PMID- 22673548 TI - Mycotic left main coronary artery aneurysm following double-valve replacement for active infective endocarditis. AB - A 68-year-old man underwent double-valve replacement (DVR) for active infective endocarditis caused by Enterococcus faecalis. Postoperative coronary angiography (CAG) revealed a saccular aneurysm originating from the distal portion of LMCA with severe stenosis at the ostium of the left anterior descending (LAD) artery and left circumflex artery (LCx). Emergent surgical resection with concomitant coronary artery bypass grafting were performed.Mycotic coronary artery aneurysms have a great tendency to rupture, and this may result in cardiac tamponade and sudden death. Early recognition and prompt surgical intervention is mandatory to minimize those fatal complications. PMID- 22673549 TI - Ipsilateral jugular to distal subclavian vein transposition to relieve central venous hypertension in rescue vascular access surgery: a surgical report of 3 cases. AB - Central venous thrombosis may often arise following central venous cannulation for temporary haemodialysis access. Venous thrombosis may be clinically asymptomatic due to the presence of collateral circulation. However, if an arteriovenous (AV) fistula is prepared below the obstructed venous segment, then symptoms may occur. Central venous hypertension interferes with dialysis, compromises limb function and threatens its safety. Percutaneous treatment is mostly used. However, in some cases endovascular treatment may not be as easy and long term patency uncertain.We report our experience on 3 patients on chronic hemodialysis treatment presenting with a patent AV fistula and ipsilateral subclavian vein chronic fibrotic obstruction. They were treated by ipsilateral internal jugular to distal subclavian vein transposition. Two separate surgical incisions were performed to expose the subclavian vein distally to the occlusion and the jugular vein that was distally ligated and transposed. There was no mortality nor significant postoperative complications. Resolution of hypertensive symptoms was achieved within 3-4 weeks in all patients. The AV fistula was used for dialysis treatment starting from the first postoperative day. At follow-up (mean 13 months), there was no recurrence of upper limb venous hypertension.In patients with subclavian occlusion and ipsilateral low flow, patent AV fistula, jugular to distal subclavian vein transposition may prove useful in cases when percutaneous angioplasty is technically not feasible or long term patency is not expected. PMID- 22673550 TI - Surgical management of a ruptured pseudoaneurysm late after total arch replacement with omentoplasty. AB - Aortic pseudoaneurysm is a rare, life-threatening complication after cardiac or aortic surgery. In this article, we report reoperation on an 86-year-old man undergoing total arch replacement and omentoplasty for an infectious aortic aneurysm, 5 years previously. He was transferred to our hospital and fell into shock. Prompt drainage of the right-side pleural cavity manifested 2000 ml of blood. Computed tomography revealed contrast extravasation into a pseudoaneurysm, which arose from the proximal anastomotic site of the ascending aorta. The patient underwent emergent surgery that included an extremely careful dissection of the omentum and pericardial adherences, through the re-sternotomy. The patient recovered without neurological sequelae. PMID- 22673551 TI - Successful surgical repair of the parachute mitral valve with mitral valve regurgitation. AB - A 65-year-old woman with exercise-related dyspnea was admitted to our hospital. Transthoracic echocardiography demonstrated a large anomalous papillary muscle that originated from the posterior wall of the left ventricle and severe mitral valve regurgitation in systole. Cleft suture, 5-0 polytetrafluoroethylene sutures from a single papillary muscle to the anterior commissure leaflet (AC), 5-0 polypropylene sutures between AC and A1, and between A1 and A2, the double orifice technique, and ring plasty with 32-mm semi-rigid ring was performed. Postoperative echocardiography showed an improvement in severe mitral valve regurgitation. At the 2-month follow-up, the patient was in good health. In the present case, the elderly patient with an isolated parachute mitral valve but without any other cardiac anomaly and presenting with mitral valve regurgitation is extremely rare. This case of mitral valvuloplasty for a parachute mitral valve with a single papillary muscle in an elderly woman has not been reported before. PMID- 22673552 TI - Cardiac tamponade caused by broken sternal wire after pectus excavatum repair: a case report. AB - Complications of pectus excavatum surgery include pneumothorax, pleuritis, hemothorax, pericardial effusion, displacement of bar, pericarditis and cardiac injury, etc. This is the case of a 15-year-old boy with cardiac tamponade caused by pericarditis who had taken the operation for a pectus excavatum repair one year previously. The cause was a sternal wire which was used for attachment of the bar to sternum that had fractured and migrated through the pericardium causing a pericardial injury and a pericarditis. PMID- 22673553 TI - Preoperative pathological diagnosis of lung cancer: is it always necessary? PMID- 22673555 TI - Cardiac effects of experimental intravenous bone marrow cell transplantation after myocardial infarction. AB - OBJECTIVES: Chronic heart failure after myocardial infarction is still a serious problem without a fundamental therapy. Direct intramyocardial transplantation of bone marrow cells (BMC) is promising but difficult to perform. Therefore, cardiac effect of experimental intravenous application of BMC after myocardial infarction (MI) is evaluated. METHODS: 20 Lewis rats underwent suture ligation of the LAD. One month after the MI, they were randomized to receive either intravenous Lewis BMC or saline injection. Hearts were explanted and histologically examined another month later. Transthoracic echocardiography was performed before MI and intravenous injection as well as before explantation. RESULTS: BMC transplanted animals developed less cartilaginous metaplasia (BMC-group: 30% vs Control-group: 50%, p <0.01). Moreover, systolic thickness of the interventricular septum (IVSs) increased significantly in the BMC-group only: pre-Tx 1.4 +/- 0.5 mm vs post-Tx 2.3 +/- 0.5 mm, p = 0.02; whereas, systolic left ventricular posterior wall diameter (LVPWD) increased in the control groups only: pre-Tx 2.6 +/- 0.5 mm vs post-Tx 3.4 +/- 0.8 mm, p = 0.04. BMC transplantation showed a tendency towards a smaller infarct area (BMC group, 11% vs. Control group, 13%; p = 0.07) and increases in LVEF and FS after an intravenous injection (p = 0.08). CONCLUSION: Intravenous BMC-Tx led to less calcifying remodelling and a compensatory hypertrophy within the infarction area that probably contributes to functional recovery. PMID- 22673556 TI - Spontaneous increase in EVAHEART(r) pump flow at a constant pump speed during exercise examination. AB - PURPOSE: Ventricular assist devices have been used for the treatment of severe heart failure. Recently, many types of blood pumps have been developed to reduce major adverse events. EVAHEART(r) (Sun Medical Technology Research Corporation, Nagano, Japan) is an implantable centrifugal blood pump. In laboratory animal studies, the pump flow of EVAHEART(r) increases spontaneously during exercise with no changes in pump control parameters. However, this has not been confirmed clinically. The aim of this study was to analyze EVAHEART(r) performance during exercise. PATIENTS AND METHODS: Four male patients were implanted with an EVAHEART(r). We evaluated the performance of the EVAHEART(r) during exercise. Fixed pump speeds were maintained during each test. Measurements during exercise were peak load, peak oxygen consumption (peak VO(2)), pre exercise pump flow, and peak velocity. RESULTS: Pump flow significantly increased from 4.1 +/- 0.5 liters per minute (L/min) to 7.2 +/- 1.8 L/min during exercise. VO(2) increased from 4.0 +/- 0.7 milliliters per kilogram per minute (ml/kg/min) to 14.7 +/- 3.3 ml/kg/min. CONCLUSION: These results indicate that EVAHEART(r) may support severe heart failure patients not only under static but also under dynamic conditions. Pump flow spontaneously increased during exercise at a constant pump speed. PMID- 22673558 TI - Novel device accurately measures graft resistance and compliance to ensure quality of coronary artery bypass. AB - INTRODUCTION: The purpose of this study is to know the influence of coronary artery bypass grafting (CABG) on coronary circulation. In the present study, we evaluated CABG by using a novel flow analyzer that can calculate bypass graft resistance (Ra), resistance of the peripheral bed to which graft connects (Rp), the inertia of blood flow through the graft (L) and vascular wall compliance (C). METHODS: We performed off-pump CABG surgery on fifteen pigs assigned to the following groups (n = 5 each): normal CABG, competitive flow grafts and constrictive grafts. RESULTS: The wave pattern of 3 groups showed a clearly different form. In normal CABG and competitive flow group, we accepted a statistical difference in Rp and flow. In normal CABG and constrictive grafts. We accepted a statistical difference in Ra and flow. CONCLUSION: We can know the relationship between CABG and coronary circulation by this device in detail. This device will be useful for evaluating graft performance during CABG. PMID- 22673560 TI - The dwelling space of postnatal care. AB - BACKGROUND: This paper considers the dwelling space of postnatal care, how being there feels for the woman going through the experience of matrescence. The research takes a hermeneutic approach and draws on philosophical notions from Heidegger. QUESTION: 'What is the nature of the dwelling space of valued postnatal care?'. METHODS: Appropriate ethics approval was gained. Participants were midwives, nurses, women, and other relevant stakeholders. There were 4 focus groups involving 11 participants and 19 individual interviews. Data collection was conducted over a one week period by a team of three researchers. An interview schedule had been organised by the administrator at the Centre. Participants chose whether to come to the centre to be interviewed, or be interviewed in their own homes. Most interviews were an hour. All interviews were tape recorded and transcribed, with the participant's permission. Data was analysed through a hermeneutic process set in the context of related literature. FINDINGS: When women are invited into a dwelling space that strengthens them they feel 'mothered': being listened to, have their needs anticipated, and are cared for in a loving manner. In such a way they grow confidence. A child health nurse reported the difference such care made to on-going mothering at home. IMPLICATIONS FOR PRACTICE: All women deserve a dwelling space in their early days of matrescence. Small birthing centres perhaps achieve such care and ambience more easily than large institutional units. Nevertheless, wherever the place, practices need to be enabled that foster the spirit of dwelling. PMID- 22673561 TI - A ratiometric fluorescent chemosensor for iron: discrimination of Fe2+ and Fe3+ and living cell application. AB - A newly designed probe, 6-thiophen-2-yl-5,6-dihydrobenzo[4,5]imidazo-[1,2-c] quinazoline (HL(1)) behaves as a highly selective ratiometric fluorescent sensor for Fe(2+) at pH 4.0-5.0 and Fe(3+) at pH 6.5-8.0 in acetonitrile-HEPES buffer (1/4) (v/v) medium. A decrease in fluorescence at 412 nm and increase in fluorescence at 472 nm with an isoemissive point at 436 nm with the addition of Fe(2+) salt solution is due to the formation of mononuclear Fe(2+) complex [Fe(II)(HL)(ClO(4))(2)(CH(3)CN)(2)] (1) in acetonitrile-HEPES buffer (100 mM, 1/4, v/v) at pH 4.5 and a decrease in fluorescence at 412 nm and increase in fluorescence at 482 nm with an isoemissive point at 445 nm during titration by Fe(3+) salt due to the formation of binary Fe(3+) complex, [Fe(III)(L)(2)(ClO(4))(H(2)O)] (2) with co-solvent at biological pH 7.4 have been established. Binding constants (K(a)) in the solution state were calculated to be 3.88 * 10(5) M(-1) for Fe(2+) and 0.21 * 10(3) M(-1/2) for Fe(3+) and ratiometric detection limits for Fe(2+) and Fe(3+) were found to be 2.0 MUM and 3.5 MUM, respectively. The probe is a "naked eye" chemosensor for two states of iron. Theoretical calculations were studied to establish the configurations of probe iron complexes. The sensor is efficient for detecting Fe(3+)in vitro by developing a good image of the biological organelles. PMID- 22673562 TI - The characterization of the neutralizing bovine viral diarrhea virus monoclonal antibodies and antigenic diversity of E2 glycoprotein. AB - Bovine viral diarrhea virus (BVDV) is associated with a range of economically important diseases of cattle including reproductive disorders and an acute fatal hemorrhagic disease. Neutralizing antibodies that bind to the E2 glycoprotein are important predictors of vaccinal immunity. Neutralization tests using the NADL strain of BVDV and five anti-E2 monoclonal antibodies showed one, Wb163, neutralized the NADL strain of BVDV in an unexpected manner. Its titer was 10,000 compared to <35 as reported previously. The present stock of NADL differed from that of the earlier study in that the amino acid at position 79 of E2 was Valine instead of Glutamic acid. MAb Wb163 may, however, recognize a less important neutralizing epitope than another mAb Wb166, because it was less cross reactive than mAb Wb166, had a neutralizing titer 50-fold lower than Wb166 and was of lower relative affinity than Wb166. Variations in the amino terminus of E2 will be discussed in the context of vaccinal immunity. PMID- 22673563 TI - Emergence of Salmonella enterica serovar infantis harboring IncI1 plasmid with bla(CTX-M-14) in a broiler farm in Japan. AB - Cefotaxime (CTX)-resistant and -susceptible Salmonella enterica serovar Infantis isolates obtained from broilers raised on a farm in January 2010 in Japan were characterized to establish their resistance determinants. The CTX-resistant isolates produced CTX-M-14 extended-spectrum beta-lactamase and harbored 2 distinct plasmid of approximately 140- and 95-kb, whereas the CTX-susceptible isolates harbored one 140-kb plasmid. The 95-kb plasmids were replicon typed as IncI1 carrying the bla(CTX-M-14) gene, while the 140-kb plasmids were IncP and harbored the aphA1, aadA1, tetA, and sul1 genes. Genetic fingerprinting by pulsed field gel electrophoresis revealed similar macrorestriction profiles amongst CTX resistant and susceptible isolates, suggesting a clonal relationship. The presence of CTX-resistant S. Infantis on a broiler farm has occurred through the acquisition of IncI1 resistance plasmid. PMID- 22673564 TI - Novel murine norovirus-like genes in wild rodents in Japan. AB - Novel murine norovirus (MNV)-like sequences were detected in 7 (14.9%) of 47 fecal and intestinal samples obtained from wild rodents in Japan. Sequencing and genetic analyses of the 7 MNV-like genes, 6 derived from Apodemus speciosus and 1 from Rattus rattus, suggested that these sequences form a cluster distinct from known MNV within genogroup V and differed even among clusters of wild rodents. Considering these results, MNV might be genetically diverse depending on the host species or distribution. This is the first report suggesting the prevalence of MNV in A. speciosus and R. rattus. PMID- 22673565 TI - Duodenal adenocarcinoma with neuroendocrine features in a patient with acromegaly and thyroid papillary adenocarcinoma: a unique combination of endocrine neoplasia. AB - A 67-year-old woman with familial clustering of thyroid papillary adenocarcinoma was diagnosed with acromegaly due to pituitary macroadenoma. She had multiple skin vegetations, but had no parathyroid and pancreas diseases. Before transsphenoidal surgery, she was further diagnosed as having a duodenal tumor and multiple hypervascular liver nodules. Biopsy specimens from the duodenal tumor and liver nodules were diagnosed histologically as moderately differentiated adenocarcinoma. Immunohistochemically, the tumor cells were positive for chromogranin, synaptophysin and somatostatin receptor 2a, suggestive for neuroendocrine features. After surgery, the patient was not in biochemical remission, and octreotide treatment was initiated. The duodenal cancer was treated with chemotherapy (neoadjuvant cisplatin and S-1). After 24 months, the patient's insulin-like growth factor I level had been normalized, and her liver tumors had not progressed macroscopically. This is a rare case of acromegaly associated with multiple endocrine tumors, not being categorized as conventional multiple endocrine neoplasia. Octreotide treatment might have had beneficial effects on our patient's duodenal adenocarcinoma and liver metastases, both directly via SSTR2a and indirectly via GH suppression, thereby contributing to their slow progression. PMID- 22673566 TI - Improvement in beta-cell function after diet-induced weight loss is associated with decrease in pancreatic polypeptide in subjects with type 2 diabetes. AB - OBJECTIVE: The aim of our study was to evaluate the effect of a lifestyle intervention program on beta-cell function and to explore the role of gastrointestinal peptides in subjects with T2D. METHODS: Subjects with T2D (n=74) received 24 weeks of intervention: 12 weeks of slimming diet (-500 kcal/day) and the subsequent 12 weeks of diet were combined with aerobic exercise. All subjects were examined at weeks 0, 12 and 24. beta-cell function was assessed during standard meal tests. Insulin secretory rate (ISR) was calculated by C-peptide deconvolution, and beta-cell function was quantified with a mathematical model. Plasma concentrations of gastrointestinal peptides were measured in a fasting state and during hyperinsulinemia induced by hyperinsulinemic isoglycemic clamp. RESULTS: Mean weight loss was 5.03+/-4.38 kg (p<0.001) in weeks 0-12. Weight did not change significantly in weeks 12-24. Both insulin secretion at the reference level and glucose sensitivity increased in weeks 0-12 (by 33%+/-54% and by 26%+/ 53%, respectively, p<0.001) and remained unchanged in weeks 12-24. Both fasting and hyperinsulinemic plasma concentrations of pancreatic polypeptide (PP) decreased in weeks 0-12 (p<0.05 for both) and did not change significantly in weeks 12-24. Changes in insulin secretion at the reference level correlated negatively with plasma concentrations of PP during hyperinsulinemia (r=-0.36; p<0.001). Changes in glucose sensitivity correlated negatively with changes in plasma concentrations of PP, both in fasting and during hyperinsulinemia (r=-0.2; p=0.01 for both). The correlations remained significant after adjustment for changes in body-mass-index. CONCLUSIONS: After diet-induced weight loss, beta cell function improved in T2D subjects and remained unchanged after the addition of exercise. We demonstrate for the first time that these changes are associated with a decrease in PP secretion. PMID- 22673567 TI - Exploring the importance of identifying geographic variation to improve diabetes treatment. PMID- 22673569 TI - NIRF/UHRF2 occupies a central position in the cell cycle network and allows coupling with the epigenetic landscape. AB - As predicted by systems biology, a paradigm shift will emerge through the integration of information about different layers of cellular processes. The cell cycle network is at the heart of the cellular computing system, and orchestrates versatile cellular functions. The NIRF/UHRF2 ubiquitin ligase is an "intermodular hub" that occupies a central position in the network, and facilitates coordination among the cell cycle machinery, the ubiquitin-proteasome system, and the epigenetic system. NIRF interacts with cyclins, CDKs, p53, pRB, PCNA, HDAC1, DNMTs, G9a, methylated histone H3 lysine 9, and methylated DNA. NIRF ubiquitinates cyclins D1 and E1, and induces G1 arrest. The NIRF gene is frequently lost in tumors and is a candidate tumor suppressor, while its paralog, the UHRF1 gene, is hardly altered. Thus, investigations of NIRF are essential to understand the entire biological systems. Through integration of the enormous information flows, NIRF may contribute to the coupling between the cell cycle network and the epigenetic landscape. We propose the new paradigm that NIRF produces the extreme diversity in the network wiring that helps the diversity of Waddington's canals. PMID- 22673570 TI - Ubiquitination and phosphorylation of Beclin 1 and its binding partners: Tuning class III phosphatidylinositol 3-kinase activity and tumor suppression. AB - The class III phosphatidylinositol 3-kinase (PI3K-III) complex and its phosphorylated lipid product phosphatidylinositol 3-phosphate (PtdIns3P) control the three topologically related membrane-involution processes autophagy, endocytosis, and cytokinesis. The activity of the catalytic unit of PI3K-III complex, the Vacuolar sorting protein 34 (VPS34), depends on the membrane targeting unit Vacuolar sorting protein 15 (VPS15), and the tumor suppressor protein Beclin 1. It is established that the overall activity of VPS34 is positively regulated by Beclin 1, whose positive influence is further controlled through the association with a set of Beclin1 interacting components, which stimulate or inhibit VPS34. The interaction between Beclin 1 and Beclin 1 associated components are controllable and is regulated by phosphorylation in a context-dependent manner. Here, we focus on an emerging concept whereby the activity of the PI3K-III complex is controlled by ubiquitination of Beclin 1 or Beclin 1-associated molecules. In summary, at least three different ubiquitin ligases can affect the positive regulatory function of Beclin 1 towards VPS34, suggesting that ubiquitination is an important and physiologically relevant event in tuning the tumor suppressor function of Beclin 1. PMID- 22673568 TI - Systemic VHL gene functions and the VHL disease. AB - The von Hippel-Lindau tumor suppressor gene (VHL) is best known as an E3 ubiquitin ligase that negatively regulates the hypoxia inducible factor (HIF). VHL mutations are the genetic defects underlying several human diseases including polycythemia, familial VHL tumor syndrome and sporadic renal cell carcinoma. VHL mutations can lead to cell-autonomous phenotypes in the tumor cells. However, non tumor cell-autonomous functions of VHL have also been noted. VHL tumor-derived cytokines can promote inflammation and induce mobilization of endothelial progenitor cells. Up-regulation of HIF caused by VHL loss-of-function mutants, including heterozygotes, has been shown to increase the activities of hematopoietic stem cells, endothelial cells and myeloid cells. As such, systemic functions of VHL likely play important roles in the development of VHL disease. PMID- 22673571 TI - Genomic analysis of ICEVchBan8: An atypical genetic element in Vibrio cholerae. AB - Genomic islands (GIs) and integrative conjugative elements (ICEs) are major players in bacterial evolution since they encode genes involved in adaptive functions of medical or environmental importance. Here we performed the genomic analysis of ICEVchBan8, an unusual ICE found in the genome of a clinical non toxigenic Vibrio cholerae O37 isolate. ICEVchBan8 shares most of its genetic structure with SXT/R391 ICEs. However, this ICE codes for a different integration/excision module is located at a different insertion site, and part of its genetic cargo shows homology to other pathogenicity islands of V. cholerae. PMID- 22673572 TI - Catalytic promiscuity in Pseudomonas aeruginosa arylsulfatase as an example of chemistry-driven protein evolution. AB - In recent years, it has become increasingly clear that many enzymes are catalytically "promiscuous". This can provide a springboard for protein evolution, allowing enzymes to acquire novel functionality without compromising their native activities. We present here a detailed study of Pseudomonas aeruginosa arylsulfatase (PAS), which catalyzes the hydrolysis of a number of chemically distinct substrates, with proficiencies comparable to that towards its native reaction. We demonstrate that the main driving force for the promiscuity is the ability to exploit the electrostatic preorganization of the active site for the native substrate, providing an example of chemistry-driven protein evolution. PMID- 22673573 TI - Cyclic AMP-specific phosphodiesterase, PDE8A1, is activated by protein kinase A mediated phosphorylation. AB - The cyclic AMP-specific phosphodiesterase PDE8 has been shown to play a pivotal role in important processes such as steroidogenesis, T cell adhesion, regulation of heart beat and chemotaxis. However, no information exists on how the activity of this enzyme is regulated. We show that under elevated cAMP conditions, PKA acts to phosphorylate PDE8A on serine 359 and this action serves to enhance the activity of the enzyme. This is the first indication that PDE8 activity can be modulated by a kinase, and we propose that this mechanism forms a feedback loop that results in the restoration of basal cAMP levels. PMID- 22673574 TI - HIF-1alpha protein is upregulated in HIF-2alpha depleted cells via enhanced translation. AB - The hypoxia-inducible factors HIF-1 and HIF-2 are primarily regulated via stabilization of their respective ?-subunits under hypoxic conditions. Previously, compensatory upregulation of one HIF-alpha-subunit upon depletion of the other alpha-subunit was described, yet the underlying mechanism remained elusive. Here we provide evidence that enhanced HIF-1alpha protein expression in HIF-2alpha knockdown (k/d) cells neither results from elevated HIF-1alpha mRNA expression, nor from increased HIF-1alpha protein stability. Instead, we identify enhanced HIF-1alpha translation as molecular mechanism. Moreover, we found elevated levels of the RNA-binding protein HuR and provide evidence that HuR is critical for the compensatory HIF-1alpha regulation in HIF-2alpha k/d cells. PMID- 22673575 TI - Anammox organism KSU-1 expresses a NirK-type copper-containing nitrite reductase instead of a NirS-type with cytochrome cd1. AB - Anaerobic ammonium oxidation (anammox) and denitrification are two distinct microbial reactions relevant to the global nitrogen cycle. The proposed initial step of the anammox reactions, reduction of nitrite to nitric oxide, has been postulated to be identical to that in denitrification catalyzed by the dissimilatory nitrite reductase of the cytochrome cd(1)-type. Here, we characterized the copper-containing nitrite reductase homolog encoded by nirK detected in the genome of an anammox bacterium strain KSU-1. We hypothesize that this NirK-type nitrite reductase, rather than a nitrite reductase of the cytochrome cd(1)-type (NirS), is likely to catalyze nitrite reduction in anammox organism KSU-1. PMID- 22673576 TI - Inducing phase-locking and chaos in cellular oscillators by modulating the driving stimuli. AB - Inflammatory responses in eucaryotic cells are often associated with oscillations in the nuclear-cytoplasmic translocation of the transcription factor NF-kB. In most laboratory realizations, the oscillations are triggered by a cytokine stimulus. We use a mathematical model to show that an oscillatory external stimulus can synchronize the NF-kB oscillations into states where the ratios of the internal to external frequency are close to rational numbers. We predict a response diagram of the TNF-driven NF-kB system which exhibits bands of synchronization known as "Arnold tongues". We suggest that when the amplitude of the external stimulus exceeds a certain threshold, chaotic dynamics of the nuclear NF-kB concentration may occur. This behavior seems independent of the shape of the external oscillation and the non-linearities transducing this signal. PMID- 22673577 TI - Novel amphiphilic compounds effectively inactivate the vaccinia virus. AB - Recent studies demonstrated the ability of artificial ribonucleases (aRNases, small organic RNA cleaving compounds) to inactivate RNA-viruses via the synergetic effect of viral RNA cleavage and disruption of viral envelope [1,2]. Herein, we describe the antiviral activity of aRNases against DNA-containing vaccinia virus: screening of aRNases of various structures revealed that amphiphilic compounds built of positively charged 1,4-diazabicyclo[2.2.2] octane substituted at the bridge nitrogen atoms with aliphatic residues efficiently inactivate this virus. The first stage was the destruction of viral membrane and structure of surface proteins (electron microscopy data). Thus, 1,4 diazabicyclo[2.2.2] octane-based aRNases are novel universal agents inactivating both RNA- and DNA-containing viruses. PMID- 22673578 TI - Group IVA phospholipase A2 optimizes ovulation and fertilization in rodents through induction of and metabolic coupling with prostaglandin endoperoxide synthase 2. AB - Female mice lacking group IVA phospholipase A(2) (Pla2g4a(-/-)) have a smaller litter size, which is due, in part, to defective implantation. We examined PLA(2)G4A dependence of the processes of ovulation and fertilization. Following induction of ovulation by equine chorionic gonadotropin (eCG)/human CG (hCG) treatment and mating, ovulation and fertilization rates were reduced significantly in Pla2g4a(-/-) mice as compared to wild-type littermates. Human CG triggered robust ovarian prostaglandin (PG) E(2) production in the preovulatory period that was significantly attenuated in Pla2g4a(-/-) mice. Human CG transiently enhanced ovarian expression of PLA(2)G4A and prostaglandin endoperoxide synthase 2 (PTGS2) in wild-type mice. This PTGS2 induction was decreased in Pla2g4a(-/-) mice and also in immature rats treated with the PLA(2)G4A inhibitor, archidonyl trifluoromethyl ketone. A close spatiotemporal association of PLA(2)G4A with PTGS2 was found in mouse and rat preovulatory follicles examined by immunohistochemistry. Less association was observed with 4 other forms of PLA(2). Our data strongly suggest that PLA(2)G4A amplifies hCG induction of PTGS2 and colocalizes with the induced PTGS2, thus contributing to robust PG production required for optimal ovulation and fertilization in rodents. PMID- 22673580 TI - Effect of climate and farm environment on Campylobacter spp. colonisation in Norwegian broiler flocks. AB - Campylobacteriosis is the most frequently reported zoonosis in the EU. A recent report states that between 50% and 80% of the human campylobacteriosis cases could be attributed to broiler as a reservoir. The current study was conducted to investigate associations between the presence of Campylobacter spp. in Norwegian broiler flocks and factors related to the climate and the farm environment. Data from 18,488 broiler flocks from 623 different farms during 2002-2007 were included in the study. A logistic regression analysis was conducted where Campylobacter spp. status of a broiler flock at the time of slaughter was defined as the dependent variable and farm was modelled as a random effect. The following factors were found to increase the probability for a broiler flock to test positive for Campylobacter spp.: daily mean temperature above 6 degrees C during the rearing period, private water supply, presence of other livestock farms within a distance of 2 km, presence of other broiler farms within a distance of 4 km with flocks positive for Campylobacter spp. within 30 days prior to slaughter, heavy rainfall 11-30 days prior to slaughter, region and year. Daily mean temperature below 0 degrees C reduced the probability. The study emphasises the importance of the farm environment and the climate for the occurrence of Campylobacter spp. in broiler flocks. The farm environment is probably a part of the Campylobacter spp. pathway into and between broiler flocks where farmyard run off and humans or flies entering the houses might constitute vehicles transporting the organism. Fly activity is temperature-driven and flies might be a part of the explanation of the increased risk for Campylobacter spp. related to increased temperature demonstrated in the study. PMID- 22673581 TI - Anthropogenic and environmental risk factors for rabies occurrence in Bhutan. AB - Anthropogenic and environmental factors were assessed as predictors of sub districts in Bhutan that reported rabies in domestic animals during the period 1996-2009. Rabies surveillance data were retrieved from the Veterinary Information System database. Anthropogenic and environmental information were obtained from public data sources. Using the total number of rabies cases reported in domestic animals, the 205 sub-districts of Bhutan were categorized as those sub-districts that reported rabies and those that did not report rabies (n=146). Logistic regression models were fit to the data and odds ratios and 95% confidence intervals were estimated. Sub-districts that share a border with India (OR 10.43; 95% CI: 4.42-24.64; P<0.001); sub-districts connected by major roads (OR 3.09; 95% CI: 1.24-7.68; P=0.015); and greater human population density (OR 3.26; 95% CI: 1.48-7.21, P=0.003) were significantly associated with a sub district reporting animal rabies in Bhutan during 1996-2009. Results suggest that human population characteristics play an important role in rabies occurrence. PMID- 22673579 TI - Biomechanics-driven chondrogenesis: from embryo to adult. AB - Biomechanics plays a pivotal role in articular cartilage development, pathophysiology, and regeneration. During embryogenesis and cartilage maturation, mechanical stimuli promote chondrogenesis and limb formation. Mechanical loading, which has been characterized using computer modeling and in vivo studies, is crucial for maintaining the phenotype of cartilage. However, excessive or insufficient loading has deleterious effects and promotes the onset of cartilage degeneration. Informed by the prominent role of biomechanics, mechanical stimuli have been harnessed to enhance redifferentiation of chondrocytes and chondroinduction of other cell types, thus providing new chondrocyte cell sources. Biomechanical stimuli, such as hydrostatic pressure or compression, have been used to enhance the functional properties of neocartilage. By identifying pathways involved in mechanical stimulation, chemical equivalents that mimic mechanical signaling are beginning to offer exciting new methods for improving neocartilage. Harnessing biomechanics to improve differentiation, maintenance, and regeneration is emerging as pivotal toward producing functional neocartilage that could eventually be used to treat cartilage degeneration. PMID- 22673582 TI - Usefulness of food chain information provided by Dutch finishing pig producers to control antibiotic residues in pork. AB - The EU prescribes that food business operators must use food chain information to assist in food safety control. This study analyses usefulness of food chain information about antibiotic usage covering the 60-day period prior to delivery of pigs to slaughter in the control of antibiotic residues in pork. A dataset with 479 test results for antibiotic residues in tissue samples of finishing pigs delivered to a Dutch slaughter company was linked to information provided by pig producers about antibiotic usage in these finishing pigs. Results show that twice as many producers reported using antibiotics in the group of 82 producers with antibiotic residues (11.0%) compared to the group without antibiotic residues (5.5%) (p=0.0686). For 89% of consignments with a finishing pig with antibiotic residues, the producer reported 'did not use antibiotics'. Food chain information about antibiotic usage provided by Dutch pig producers was no guarantee for absence of antibiotic residues in delivered finishing pigs. PMID- 22673583 TI - Sexual function in pre- and post-menopausal women with obstructive sleep apnea syndrome. AB - The objective of this study was to evaluate the female sexual function in relation to hormonal status in pre- and postmenopausal women with obstructive sleep apnea (OSA). A total of 43 premenopausal (mean age 42.1+/-4.9) and 58 postmenopausal (mean age 59.9+/-4.8) women were included in the study. All women filled out the Epworth sleepiness scale (ESS), the Beck Depression Inventory (BDI) and the Female Sexual Function Index (FSFI). Testosterone, estradiol and progesterone were measured. After polysomnography, women were allocated to a not severe OSA group (Apnea-Hypopnea Index (AHI) 10-30) and a severe OSA group (AHI >30). Healthy subjects comprised the control group. Severe OSA women in both pre- and post-menopausal group were found to have significantly lower mean FSFI score (16.5+/-4.0 and 16.9+/-4.7, respectively) compared with not-severe OSA (23.4+/ 5.5, P<0.01 and 21.8+/-7.5, P<0.05) and control subjects (27.0+/-5.5, P<0.01 and 24.0+/-6.7, P<0.01). Progesterone, which was significantly lower in severe OSA premenopausal women (0.26+/-0.2) compared with not-severe OSA (0.55+/-0.14, P<0.01) and control group (0.62+/-0.16, P<0.01), correlated significantly with FSFI (r=0.39, P<0.01). Our study demonstrated that OSA is associated with sexual dysfunction in both premenopausal and postmenopausal women in a dose-related fashion. Regarding premenopausal women, our results indicated that progesterone may play a role in the association between OSA and female sexual dysfunction. PMID- 22673584 TI - Radiological evaluation by magnetic resonance of the 'new anatomy' of transsexual patients undergoing male to female sex reassignment surgery. AB - Magnetic resonance (MR) is the best way to assess the new anatomy of the pelvis after male to female (MtF) sex reassignment surgery. The aim of the study was to evaluate the radiological appearance of the small pelvis after MtF surgery and to compare it with the normal women's anatomy. Fifteen patients who underwent MtF surgery were subjected to pelvic MR at least 6 months after surgery. The anthropometric parameters of the small pelvis were measured and compared with those of ten healthy women (control group). Our personal technique (creation of the mons Veneris under the pubic skin) was performed in all patients. In patients who underwent MtF surgery, the mean neovaginal depth was slightly superior than in women (P=0.009). The length of the inferior pelvic aperture and of the inlet of pelvis was higher in the control group (P<0.005). The inclination between the axis of the neovagina and the inferior pelvis aperture, the thickness of the mons Veneris and the thickness of the rectovaginal septum were comparable between the two study groups. MR consents a detailed assessment of the new pelvic anatomy after MtF surgery. The anthropometric parameters measured in our patients were comparable with those of women. PMID- 22673585 TI - Spatial, temporal, and speciation variations of heavy metals in sediments of Nan'ao Island, a representative mariculture base in Guangdong coast, China. AB - Heavy metals in sediments from Baisha Bay, Nan'ao Island, one of Guangdong Province's largest mariculture bases in Southern China, were investigated. The results display that the concentrations of 6 heavy metals from surface sediments were 0.040-0.220 (Cd), 24.22-39.61 (Pb), 25.30-42.66 (Cr), 10.83-19.54 (Ni), 15.06-39.24 (Cu) and 55.12-141.73 mg kg(-1) (Zn), respectively. The highest concentrations and the greatest increasing rates of heavy metals were found in a sediment core in a fish cage culture area due to receiving sewage discharge, uneaten fish bait, and boat gasoline combustion. Cd was preferentially associated with the acid-soluble fraction and Pb mainly with the reducible fraction in surface sediments. Meanwhile, Cd and Pb displayed greatest labile fractions, indicating anthropogenic origin. A principal component analysis (PCA) revealed three groupings (Cd; Cr, Ni and Cu; Pb and Zn) that mainly result from different distributions of the metals in the various fractions. The ecological risk of the polluted sediments stemmed mainly from Cd, and from Pb and Cu to a lesser degree. It is suggested that the density of fish-stocking be controlled, periodic movement of rafts (cages) be introduced, and the total numbers of net-cages and human activities in the mariculture zones be restricted. in order to facilitate the recovery of the polluted sediment. PMID- 22673586 TI - Rectal cancer management and high levels of anxiety and depression. PMID- 22673587 TI - At loose ends: telomere theories of aging and cancer begin to converge. PMID- 22673589 TI - Cutaneous T-cell lymphoma's confounding nature. PMID- 22673591 TI - Mirth and medicine: hope or hype? PMID- 22673590 TI - Avastin saga reveals debate over clinical trial endpoints. PMID- 22673593 TI - Impact of preoperative nutritional support on clinical outcome in abdominal surgical patients at nutritional risk. AB - OBJECTIVE: This multicenter, prospective cohort study evaluated the effect of preoperative nutritional support in abdominal surgical patients at nutritional risk as defined by the Nutritional Risk Screening Tool 2002 (NRS-2002). METHODS: A consecutive series of patients admitted for selective abdominal surgery in the Peking Union Medical College Hospital and the Beijing University Third Hospital in Beijing, China were recruited from March 2007 to July 2008. Data were collected on the nutritional risk screening (NRS-2002), the application of perioperative nutritional support, surgery, complications, and length of stay. A minimum of 7 d of parenteral nutrition or enteral nutrition before surgery was considered adequate preoperative nutritional support. RESULTS: In total 1085 patients were recruited, and 512 of them were at nutritional risk. Of the 120 patients with an NRS score at least 5, the complication rate was significantly lower in the preoperative nutrition group compared with the control group (25.6% versus 50.6%, P = 0.008). The postoperative hospital stay was significantly shorter in the preoperative nutrition group than in the control group (13.7 +/- 7.9 versus 17.9 +/- 11.3 d, P = 0.018). Of the 392 patients with an NRS score from 3 to 4, the complication rate and the postoperative hospital stay were similar between patients with and those without preoperative nutritional support (P = 1.0 and 0.770, respectively). CONCLUSION: This finding suggests that preoperative nutritional support is beneficial to patients with an NRS score at least 5 by lowering the complication rate. PMID- 22673594 TI - Effect of low-calorie versus low-carbohydrate ketogenic diet in type 2 diabetes. AB - OBJECTIVE: Effective diabetic management requires reasonable weight control. Previous studies from our laboratory have shown the beneficial effects of a low carbohydrate ketogenic diet (LCKD) in patients with type 2 diabetes after its long term administration. Furthermore, it favorably alters the cardiac risk factors even in hyperlipidemic obese subjects. These studies have indicated that, in addition to decreasing body weight and improving glycemia, LCKD can be effective in decreasing antidiabetic medication dosage. Similar to the LCKD, the conventional low-calorie, high nutritional value diet is also used for weight loss. The purpose of this study was to understand the beneficial effects of LCKD compared with the low-calorie diet (LCD) in improving glycemia. METHODS: Three hundred and sixty-three overweight and obese participants were recruited from the Al-Shaab Clinic for a 24-wk diet intervention trial; 102 of them had type 2 diabetes. The participants were advised to choose LCD or LDKD, depending on their preference. Body weight, body mass index, changes in waist circumference, blood glucose level, changes in hemoglobin and glycosylated hemoglobin, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, uric acid, urea and creatinine were determined before and at 4, 8, 12, 16, 20, and 24 wk after the administration of the LCD or LCKD. The initial dose of some antidiabetic medications was decreased to half and some were discontinued at the beginning of the dietary program in the LCKD group. Dietary counseling and further medication adjustment were done on a biweekly basis. RESULTS: The LCD and LCKD had beneficial effects on all the parameters examined. Interestingly, these changes were more significant in subjects who were on the LCKD as compared with those on the LCD. Changes in the level of creatinine were not statistically significant. CONCLUSION: This study shows the beneficial effects of a ketogenic diet over the conventional LCD in obese diabetic subjects. The ketogenic diet appears to improve glycemic control. Therefore, diabetic patients on a ketogenic diet should be under strict medical supervision because the LCKD can significantly lower blood glucose levels. PMID- 22673595 TI - Effects of supplemental dietary arginine on the exogenous advanced glycosylation end product-induced interleukin-23/interleukin-17 immune response in rats. AB - OBJECTIVES: Arginine (Arg) is known to possess numerous useful physiological properties and immunomodulatory effects. Th17 cells are a unique T-helper cell lineage. Regulation of Th17 cells plays a significant role in the pathogenesis of inflammatory disorders. This study investigated the effect of Arg on the exogenous advanced glycosylation end product (AGE)-induced Th17-mediated immune response. METHODS: Rats were randomly divided into three groups. The control BSA (CB) group was fed a common diet and given a tail vein injection of non-glycated bovine serum albumin (BSA). The control AGE (CA) group was fed the common diet and injected with 2 mg AGE-BSA. Arg-AGE (AA) group was fed the Arg-supplemented diet and injected with 2 mg AGE-BSA. The experimental diets were identical in energy and nutrient distributions except for the amino acid content. Arg provided 2% of the total energy. Tail vein injections and diets were given daily. After 10 d, all rats were sacrificed, and blood samples were collected for further analysis. RESULTS: The AA group had the highest inducible nitric oxide (NO) synthase expression and plasma NO levels. The percentage of Foxp3 T-regulatory cells in the AA group was lower than those of the CA and CB groups. Transforming growth factor-beta1, interleukin (IL)-6, and IL-17A gene expression was higher in the AGE-administered groups. The AA group had higher TGF-beta1 and IL-17A expression than did the CA group. CONCLUSION: These results suggest that in a condition of exogenous AGE administration, supplemental dietary Arg resulted in a more pronounced IL-23/IL-17 immune response, possibly by increasing NO secretion. PMID- 22673596 TI - Glycerophosphocholine enhances growth hormone secretion and fat oxidation in young adults. AB - OBJECTIVE: alpha-Glycerophosphocholine (GPC) is a putative acetylcholine precursor that potentially increases growth hormone secretion through the action of acetylcholine-stimulated catecholamine. The aim of this study was to investigate acute physiologic responses to a single intake of GPC. METHODS: Eight healthy male subjects (25 +/- 1 y old) ingested GPC 1000 mg or a placebo in a double-blind randomized crossover study. Fasting blood samples were obtained before the administration of GPC (baseline) and 60 and 120 min after administration. All subjects repeated the identical protocol using the placebo. RESULTS: Plasma free choline levels significantly increased at 60 and 120 min after GPC administration. Plasma growth hormone secretion was increased significantly 60 min after taking GPC, whereas no significant change was observed with the placebo. In addition, the serum free fatty acid was increased 120 min after GPC ingestion, but no changes were seen with the placebo. Moreover, serum acetoacetate and 3-hydroxybutyrate levels, which are indices of hepatic fat oxidation, were increased at 120 min after taking GPC, whereas the placebo had no effect. CONCLUSION: These findings suggest that a single dose of GPC increases growth hormone secretion and hepatic fat oxidation, with concomitant increases in choline levels, in young adults. PMID- 22673597 TI - Predicting personalized multiple birth risks after in vitro fertilization-double embryo transfer. AB - OBJECTIVE: To report and evaluate the performance and utility of an approach to predicting IVF-double embryo transfer (DET) multiple birth risks that is evidence based, clinic-specific, and considers each patient's clinical profile. DESIGN: Retrospective prediction modeling. SETTING: An outpatient university-affiliated IVF clinic. PATIENT(S): We used boosted tree methods to analyze 2,413 independent IVF-DET treatment cycles that resulted in live births. The IVF cycles were retrieved from a database that comprised more than 33,000 IVF cycles. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The performance of this prediction model, MBP-BIVF, was validated by an independent data set, to evaluate predictive power, discrimination, dynamic range, and reclassification. RESULT(S): Multiple birth probabilities ranging from 11.8% to 54.8% were predicted by the model and were significantly different from control predictions in more than half of the patients. The prediction model showed an improvement of 146% in predictive power and 16.0% in discrimination over control. The population standard error was 1.8%. CONCLUSION(S): We showed that IVF patients have inherently different risks of multiple birth, even when DET is specified, and this risk can be predicted before ET. The use of clinic-specific prediction models provides an evidence based and personalized method to counsel patients. PMID- 22673598 TI - Comparison of oral robenacoxib and carprofen for the treatment of osteoarthritis in dogs: a randomized clinical trial. AB - The efficacy and tolerability of robenacoxib for the treatment of osteoarthritis in dogs were evaluated in a prospective, multicenter, randomized, noninferiority design clinical trial. A total of 32 dogs presenting with osteoarthritis were allocated randomly to receive, orally once daily for 28 days, either 1-2 mg/kg robenacoxib (n=21) or 3.5-5 mg/kg carprofen (n=11). Dogs were assessed by clinicians and owners using numerical rating scale scores at baseline and days 14 and 28. The primary efficacy endpoint was the global functional disability score, which was the sum of clinician scores for standing posture, lameness at walk, lameness at trot, willingness to raise the contralateral limb and pain at palpation. There was a good to excellent level of efficacy in both treatment groups. Differences between days 14 and 28 compared to day 0 were significant for all 11 clinician and owner scores for robenacoxib, and for 6 of 11 scores for carprofen. The efficacy of robenacoxib was numerically superior to carprofen for all 13 endpoints, but differences were not statistically significant. For the global functional disability score, the estimated efficacy of robenacoxib was 1.244 (95% confidence interval 0.555-2.493) relative to carprofen. The tolerability of both treatments was good as assessed from adverse events, clinical signs, and hematology and serum biochemistry variables. In conclusion, once daily administration of robenacoxib tablets had noninferior efficacy and tolerability compared to carprofen for the treatment of the clinical signs of osteoarthritis in dogs. PMID- 22673599 TI - Calf form bovine leukosis with lameness in a Holstein heifer. AB - A 12-month-old Holstein heifer with anorexia, lameness, and enlargement of peripheral lymph nodes was suspected of having bovine leukosis. Although lymphocytosis was not observed, cytology of fine needle aspirate from a superficial cervical node, and increased serum lactate dehydrogenase and thymidine kinase activities, strongly suggested lymphosarcoma. Increased numbers of mononuclear cells as well as mitotic cells were observed in synovial fluid collected from swollen joints. Pathological examination confirmed B-cell calf form bovine leukosis and joint swelling related to neoplastic cell infiltration. Both interleukin-2 receptor and thymidine kinase 1 genes were highly expressed in cells from superficial cervical lymph node aspirate. PMID- 22673600 TI - Evaluation of the effectiveness of sarpogrelate on the surrogate markers for macrovascular complications in patients with type 2 diabetes. AB - Sarpogrelate, a selective 5-HT(2) receptor antagonist, is known to have a significant effect on antiplatelet action. This study was a double-blinded, randomized, paralleled multicenter trial to compare the effects of sarpogrelate and aspirin on preventing macrovascular complications in patients with type 2 diabetes. The subjects were randomly assigned to either the sarpogrelateor the aspirin group. The baseline parameters for macrovascular complications, such as intima media thickness (IMT), ankle-brachial index (ABI), IL-6, serotonin, adiponectin, and hsCRP, were measured before drug administration. Changes were compared at 6 and 12 months after the administration of each drug. A total of 127 subjects (63 in the sarpogrelate group and 64 in the aspirin group) were pooled during the study period. No significant differences were found in baseline IMT or in other predictors of macrovascular complications. The mean IMT increased in both groups after 12 months, but there was no significant difference between the two groups. No significant change was found in the other predictors of macrovascular complications nor in the incidence of drug-related adverse events between the two groups. During the study period, no significant differences were found between the sarpogrelate group and aspirin group in the clinical indices or in the safety of the subjects related to macrovascular complications. This suggests that sarpogrelate may be clinically useful for the primary prevention of macrovascular complications in patients with type 2 diabetes. PMID- 22673601 TI - Delay in the diagnosis of multiple endocrine neoplasia type 1: typical symptoms are frequently overlooked. AB - The morbidity and mortality of individuals with multiple endocrine neoplasia type 1 (MEN1) can be reduced by early diagnosis of MEN1 and related endocrine tumors. To find factors contributing to early diagnosis, we collected clinical information on MEN1 patients through a MEN study group, "MEN Consortium of Japan" and analyzed the time of initial symptom-dependent detection of parathyroid tumors, gastro-entero-pancreatic neuroendocrine tumors (GEPNETs) and pituitary tumors, and that of tumor detection-dependent MEN1 diagnosis in 560 patients. Main tumors were identified up to 7.0 years after symptoms appeared and there was no difference in age at the diagnosis of GEPNETs alone between probands and family members. In patients with typical symptoms (peptic ulcers, urolithiasis, fasting hypoglycemia, bone fracture/loss and amenorrhea), the mean interval between symptom manifestation and tumor detection was extended up to 9.6 years. In particular, 21.7% (5/23) of patients with amenorrhea were diagnosed with pituitary tumors in under one year. In patients with peptic ulcers (from parathyroid tumors or GEPNETs) and urolithiasis (from parathyroid tumors), the interval was positively correlated with age at tumor detection. The interval between tumor detection and MEN1 diagnosis was also prolonged to approximately four years in patients with fasting hypoglycemia (from GEPNETs) and amenorrhea. A substantial delay in the diagnosis of symptom-related tumors and subsequent MEN1 and inadequate screening of GEPNETs in family members were indicated. A greater understanding of MEN1 may assist medical practitioners to make earlier diagnoses, to share patients' medical information and to give family members sufficient disease information. PMID- 22673602 TI - Clinical trial of weekly paclitaxel chemotherapy for papillary thyroid carcinoma with squamous cell carcinoma component. AB - Papillary thyroid carcinoma (PC) can occasionally include a squamous cell carcinoma (SCC) component. In this study, we evaluated the effect of weekly paclitaxel chemotherapy in 3 patients with PC including an SCC component. None of these patients had lesions of anaplastic carcinoma on pathological examination. Weekly paclitaxel chemotherapy was performed as an induction chemotherapy for 2 patients. All 3 patients underwent locally curative surgery and weekly paclitaxel chemotherapy after surgery as an adjuvant therapy. The response to the chemotherapy was evaluated based on the RECIST guideline (version 1.1). Two patients had partial responses (PRs) and the remaining 1 had stable disease (SD). The response rate was 67% and the clinical benefit rate (PR+SD) was 100%. One patient died of the growth of lung metastases that had been detected before surgery 22 months after the diagnosis. The remaining 2 are still alive, 14 and 22 months after the diagnosis, respectively. Taken together, weekly paclitaxel may be one of the effective adjuvant therapies for PC with an SCC component. PMID- 22673603 TI - Gender stereotypes and superior conformity of the self in a sample of cyclists. AB - In the field of driving, people tend to think they are more competent and more cautious than others. This is the superior conformity of the self (SCS). Our main hypothesis was that, among cyclists, women would show a higher SCS on cautiousness, though men would show a higher SCS concerning competence. 1799 cyclists provided a self-assessment of their own cautiousness and of other people's cautiousness. The same procedure was used for competence. Consistent with the hypothesis, the SCS was gender-specific: it was more prominent for women concerning cautiousness and more prominent for men concerning competence. These results could explain why people tend to ignore the safety campaigns. They also indicate the importance of adapting messages concerning safety measures to gender. PMID- 22673604 TI - Reductions in transport mortality in Australia: evidence of a public health success. AB - OBJECTIVE: To describe trends in transport mortality for a range of common transport types in Australia over a 30-year period (1975-1977 to 2005-2007). METHODS: Mortality data on all-cause and transport-related causes of death were supplied by the Australian Institute of Health and Welfare (AIHW). Mortality rates, expected number of deaths and probabilities of death were compared for three time periods: 1975-1977, 1990-1992 and 2005-2007. RESULTS: There were significant decreasing trends between 1975-1977 and 2005-2007 in all-cause and most other transport mortality types for both men and women. There were significant reductions in the contribution of transport-related mortality to all cause mortality; however the difference in mortality between men and women (higher for men) changed little over the evaluated period. CONCLUSIONS: Between 1975-1977 and 2005-2007 there were marked reductions in key causes of transport related mortality amongst Australian adults, and the reductions in transport related mortality exceeded reductions in all-cause mortality. The reductions could be attributed to better preventive measures and improved medical treatment for people involved in transport crashes. Although there is scope for further improvement, the reductions are evidence of a success in the prevention of crashes and the medical treatment of crash victims. PMID- 22673605 TI - Successful transcatheter patent ductus arteriosus occluder embolization of a congenital left coronary artery aneurysm and fistulas draining into the right atrium. AB - Coronary artery aneurysms and fistulas are very rare congenital anomalies. They occur in 0.2%-0.4% of all congenital heart diseases. In this article, we report a case of a 39-year-old girl with a left coronary artery aneurysm and fistula draining into the right atrium. An intervention is successfully achieved by transcatheter occluder embolization using a patent ductus arteriosus (PDA) occluder. PMID- 22673606 TI - Subacute presentation of right ventricular perforation after pacemaker implantation. AB - We report an 87-year-old woman with right ventricular perforation due to a permanent pacemaker lead detected 4-days after implantation. The pacemaker lead was seen to perforate through the myocardium and pericardium and to reach the left pleural cavity. We removed the wire surgically by median sternotomy. The pericardial effusion was cloudy and yellowish, suggesting infection. However, no bacteria were detected by bacterial cultures of the pericardial effusion and pacing wire. The patient developed neither mediastinitis nor sepsis after the operation, and a new pacemaker was implanted safely one month later. PMID- 22673607 TI - Tricuspid valve surgery based on the mechanisms of functional tricuspid regurgitation. PMID- 22673608 TI - Should right coronary bypass grafts be anastomosed proximal or distal to the crux? A comparison of graft patencies. AB - AIM: Late occlusion of bypass grafts is one of the main issues associated with long-term survival after coronary artery bypass grafting (CABG) surgery. Left coronary system is generally revascularized using arterial conduits, whereas saphenous venous grafts are used for right coronary system. We investigated the prognostic factors that are related to the patency and risk of occlusion of saphenous venous grafts used for revascularization of diseased right coronary arteries. PATIENTS AND METHOD: 92 patients who underwent CABG operation including a right coronary artery (RCA) bypass using saphenous venous graft (SVG) between January 2003 and July 2010 were evaluated retrospectively. Mean time of follow up was 66.9 +/- 27.2 months (range 104-13 months). Grafts patencies were investigated using coronary angiography, and associated risk factors for mortality and morbidity were determined during the mid-term and long-term follow up. During the data collection phase, a significant association was noticed between patency of right coronary bypass grafts and site of distal anastomoses on RCA. Thus, patients were divided into two groups, according to the site of anastomosis. Right coronary anastomoses were performed either proximal (Group A, n = 44) or distal (Group B, n = 46) to the crux of the RCA (PDA). RESULTS: Patency rates were similar in-group A (50% occluded and 50% patent) whereas patency rates were significantly higher in-group B (occluded 16.7%, patent 83.3%, p = 0.001). Mean age was significantly higher in-group A compared to Group B (p <0.05); however, there was no statistically significant difference between the two groups with regard to risk factors associated with cardiovascular disease (p >0.05). Also, mean diameter of the target vessel was significantly higher in group A (p <0.01). CONCLUSION: Based on the results of our study we suggest that even though an appropriate segment for anastomosis is available proximal to the crux of the RCA, right posterior descending artery (PDA) should be preferred for revascularization when RCA is the target vessel in CABG. PMID- 22673610 TI - Sentinel node navigation surgery in early-stage esophageal cancer. AB - The sentinel node (SN) concept has revolutionized the surgical staging of both melanoma and breast cancer over the past two decades. However, the validity of the SN hypothesis has been controversial for esophageal cancer, because SN mapping for esophageal cancer is technically complicated, and the number of early stage esophageal cancer is very limited. Nevertheless previous studies nicely demonstrated that SN mapping may be feasible in patients with early-stage esophageal cancer. Transthoracic extended esophagectomy with three-field radical lymph node dissection has been recognized as a curative procedure for thoracic esophageal cancer in Japan. However, uniform application of this highly invasive procedure might increase the morbidity and markedly reduce the quality of life (QOL) after surgery. Although further accumulation of evidence based on multicenter clinical trials using a standard protocol is needed, SN mapping and SN navigation surgery would provide significant information to perform individualized selective lymphadenectomy which might reduce the morbidity and retain the patients' QOL. In addition, technical innovation including the development of new tracers is expected to confirm the accuracy and reliability of SN mapping in esophageal cancer. PMID- 22673611 TI - Haplotype data for 16 Y-chromosome STR loci in Aboriginal and Caucasian populations in South Australia. AB - Y-STR haplotype data was obtained using the AmpFlSTR((r)) YFilerTM PCR Amplification Kit (Applied Biosystems, Foster City, CA) for 1079 Caucasian and 766 Australian Aboriginal individuals. Haplotype diversity was similar in both populations, however discrimination capacity was higher in Caucasians than Aborigines (0.946 compared to 0.692). Locus DYS385, which was considered as a single locus, was the most diverse marker in both populations (0.836 in Caucasians and 0.905 in Aborigines). POPULATION: The South Australian Aboriginal and Caucasian databases were compiled from casework reference profile information held on the South Australian Criminal, Reference and Evidence DNA Database (SACREDD). Ethnicity was assigned based on self-declaration. PMID- 22673612 TI - Genetic data from Y chromosome STR and SNP loci in Ukrainian population. AB - We have tested a sample of 154 unrelated males from Lviv region (Ukraine) for 11 Y-chromosomal single nucleotide polymorphisms (SNPs) and 17 Y-chromosomal STR loci (DYS19, DYS385a, DYS385b, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635, YGATA_H4.1). Haplotype and haplogroup diversity values were calculated for the population under study. Genetic distances (R(ST)) to 9 other Slavic populations were calculated based on 12 Y-STR loci. Haplotype frequencies and MDS plots were constructed based on genetic distances. Haplogroup frequency patterns revealed in Ukraine are similar to those characteristic of other European populations. However, it also allowed for identification a specific genetic component in Ukrainian sample which seems to originate from areas dwelled by Western Slavs, i.e. subhaplogroup R1a1a7, at frequency of 13.65%. Analysis of R(ST) distances and AMOVA revealed high level of heterogeneity between Slavic populations inhabiting the south and north part of Europe, determined geographically rather than by linguistic factors. It has also been found a closer similarity (in the values of R(ST)) between Ukrainian and Slovak populations than between Ukrainians and other Slavic population samples. PMID- 22673613 TI - Stimuli-responsive peroxidase mimicking at a smart graphene interface. AB - A synergistic graphene-based catalyst was engineered by the in situ growth of "naked" Au-nanoparticles (NPs) on graphene sheets. The catalyst exhibits excellent switchable peroxidase-like activity in response to specific DNA. PMID- 22673615 TI - Denervation-induced mitochondrial dysfunction and autophagy in skeletal muscle of apoptosis-deficient animals. AB - Skeletal muscle undergoes remarkable adaptations in response to chronic decreases in contractile activity, such as a loss of muscle mass, decreases in both mitochondrial content and function, as well as the activation of apoptosis. Although these adaptations are well known, questions remain regarding the signaling pathways that mediated these changes. Autophagy is an organelle turnover pathway that could contribute to these adaptations. The purpose of this study was to determine whether denervation-induced muscle disuse would result in the activation of autophagy gene expression in both wild-type (WT) and Bax/Bak double knockout (DKO) animals, which display an attenuated apoptotic response. Denervation caused a reduction in muscle mass for WT and DKO animals; however, there was a 40% attenuation in muscle atrophy in DKO animals. Mitochondrial state 3 respiration was significantly reduced, and reactive oxygen species production was increased by two- to threefold in both WT and DKO animals. Apoptotic markers, including cytosolic AIF and DNA fragmentation, were elevated in WT, but not in DKO animals following denervation. Autophagy proteins including LC3II, ULK1, ATG7, p62, and Beclin1 were increased similarly following denervation for both WT and DKO. Interestingly, denervation markedly increased the localization of LC3II to subsarcolemmal mitochondria, and this was more pronounced in the DKO animals. Thus denervation-induced muscle disuse activates both apoptotic and autophagic signaling pathways in muscle, and autophagic protein expression does not exhibit a compensatory increase in the presence of attenuated apoptosis. However, the absence of Bax and Bak may represent a potential signal to trigger mitophagy in muscle. PMID- 22673614 TI - Inflammation alters regional mitochondrial Ca2+ in human airway smooth muscle cells. AB - Regulation of cytosolic Ca(2+) concentration ([Ca(2+)](cyt)) in airway smooth muscle (ASM) is a key aspect of airway contractility and can be modulated by inflammation. Mitochondria have tremendous potential for buffering [Ca(2+)](cyt), helping prevent Ca(2+) overload, and modulating other intracellular events. Here, compartmentalization of mitochondria to different cellular regions may subserve different roles. In the present study, we examined the role of Ca(2+) buffering by mitochondria and mitochondrial Ca(2+) transport mechanisms in the regulation of [Ca(2+)](cyt) in enzymatically dissociated human ASM cells upon exposure to the proinflammatory cytokines TNF-alpha and IL-13. Cells were loaded simultaneously with fluo-3 AM and rhod-2 AM, and [Ca(2+)](cyt) and mitochondrial Ca(2+) concentration ([Ca(2+)](mito)) were measured, respectively, using real time two-color fluorescence microscopy in both the perinuclear and distal, perimembranous regions of cells. Histamine induced a rapid increase in both [Ca(2+)](cyt) and [Ca(2+)](mito), with a significant delay in the mitochondrial response. Inhibition of the mitochondrial Na(+)/Ca(2+) exchanger (1 MUM CGP 37157) increased [Ca(2+)](mito) responses in perinuclear mitochondria but not distal mitochondria. Inhibition of the mitochondrial uniporter (1 MUM Ru360) decreased [Ca(2+)](mito) responses in perinuclear and distal mitochondria. CGP 37157 and Ru360 significantly enhanced histamine-induced [Ca(2+)](cyt). TNF-alpha and IL-13 both increased [Ca(2+)](cyt), which was associated with decreased [Ca(2+)](mito) in the case of TNF-alpha but not IL-13. The effects of TNF-alpha on both [Ca(2+)](cyt) and [Ca(2+)](mito) were affected by CGP-37157 but not by Ru360. Overall, these data demonstrate that in human ASM cells, mitochondria buffer [Ca(2+)](cyt) after agonist stimulation and its enhancement by inflammation. The differential regulation of [Ca(2+)](mito) in different parts of ASM cells may serve to locally regulate Ca(2+) fluxes from intracellular sources versus the plasma membrane as well as respond to differential energy demands at these sites. We propose that such differential mitochondrial regulation, and its disruption, may play a role in airway hyperreactivity in diseases such as asthma, where [Ca(2+)](cyt) is increased. PMID- 22673616 TI - Regulation of the human Na+-dependent glucose cotransporter hSGLT2. AB - The human Na(+)-glucose cotransporter SGLT2 is expressed mainly in the kidney proximal convoluted tubule where it is considered to be responsible for the bulk of glucose reabsorption. Phosphorylation profiling has revealed that SGLT2 exists in a phosphorylated state in the rat renal proximal tubule cortex, so we decided to investigate the regulation of human SGLT2 (hSGLT2) by protein kinases. hSGLT2 was expressed in human embryonic kidney (HEK) 293T cells, and the activity of the protein was measured using radiotracer and whole cell patch-clamp electrophysiology assays before and after activation of protein kinases. 8-Bromo adenosine cAMP (8-Br-cAMP) was used to activate protein kinase A, and sn-1,2 dioctanoylglycerol (DOG) was used to activate protein kinase C (PKC). 8-Br-cAMP stimulated D-[alpha-methyl-(14)C]glucopyranoside ([(14)C]alpha-MDG) uptake and Na(+)-glucose currents by 200% and DOG increased [(14)C]alpha-MDG uptake and Na(+)-glucose currents by 50%. In both cases the increase in SGLT2 activity was marked by an increase in the maximum rate of transport with no change in glucose affinity. These effects were completely negated by mutation of serine 624 to alanine. Insulin induced a 250% increase in Na(+)-glucose transport by wild-type but not S624A SGLT2. Parallel studies confirmed that the activity of hSGLT1 was regulated by PKA and PKC due to changes in the number of transporters in the cell membrane. hSGLT1 was relatively insensitive to insulin. We conclude that hSGLT1 and hSGLT2 are regulated by different mechanisms and suggest that insulin is an SGLT2 agonist in vivo. PMID- 22673617 TI - Kv3 channels contribute to the delayed rectifier current in small cultured mouse dorsal root ganglion neurons. AB - Delayed rectifier voltage-gated K(+) (K(V)) channels are important determinants of neuronal excitability. However, the large number of K(V) subunits poses a major challenge to establish the molecular composition of the native neuronal K(+) currents. A large part (~60%) of the delayed rectifier current (I(K)) in small mouse dorsal root ganglion (DRG) neurons has been shown to be carried by both homotetrameric K(V)2.1 and heterotetrameric channels of K(V)2 subunits with silent K(V) subunits (K(V)S), while a contribution of K(V)1 channels has also been demonstrated. Because K(V)3 subunits also generate delayed rectifier currents, we investigated the contribution of K(V)3 subunits to I(K) in small mouse DRG neurons. After stromatoxin (ScTx) pretreatment to block the K(V)2 containing component, application of 1 mM TEA caused significant additional block, indicating that the ScTx-insensitive part of I(K) could include K(V)1, K(V)3, and/or M-current channels (KCNQ2/3). Combining ScTx and dendrotoxin confirmed a relevant contribution of K(V)2 and K(V)2/K(V)S, and K(V)1 subunits to I(K) in small mouse DRG neurons. After application of these toxins, a significant TEA-sensitive current (~19% of total I(K)) remained with biophysical properties that corresponded to those of K(V)3 currents obtained in expression systems. Using RT-PCR, we detected K(V)3.1-3 mRNA in DRG neurons. Furthermore, Western blot and immunocytochemistry using K(V)3.1-specific antibodies confirmed the presence of K(V)3.1 in cultured DRG neurons. These biophysical, pharmacological, and molecular results demonstrate a relevant contribution (~19%) of K(V)3 containing channels to I(K) in small mouse DRG neurons, supporting a substantial role for K(V)3 subunits in these neurons. PMID- 22673618 TI - Hyperthermia increases interleukin-6 in mouse skeletal muscle. AB - Skeletal muscles produce and contribute to circulating levels of IL-6 during exercise. However, when core temperature is reduced, the response is attenuated. Therefore, we hypothesized that hyperthermia may be an important and independent stimulus for muscle IL-6. In cultured C2C12 myotubes, hyperthermia (42 degrees C) increased IL-6 gene expression 14-fold after 1 h and 35-fold after 5 h of 37 degrees C recovery; whereas exposure to 41 degrees C resulted in a 2.6-fold elevation at 1 h. IL-6 protein was secreted and significantly elevated in the cell supernatant. Similar but reduced responses to heat were seen in C2C12 myoblasts. Isolated soleus muscles from mice, exposed ex vivo to 41 degrees C for 1 h, yielded similar IL-6 gene responses (>3-fold) but without a significant effect on protein release. When whole animals were exposed to passive hyperthermia, such that core temperature increased to 42.4 degrees C, IL-6 mRNA in soleus increased 5.4-fold compared with time matched controls. Interestingly, TNF-alpha gene expression was routinely suppressed at all levels of hyperthermia (40.5-42 degrees C) in the isolated models, but TNF-alpha was elevated (4.2-fold) in the soleus taken from intact mice exposed, in vivo, to hyperthermia. Muscle HSP72 mRNA increased as a function of the level of hyperthermia, and IL-6 mRNA responses increased proportionally with HSP72. In cultured C2C12 myotubes, when heat shock factor was pharmacologically blocked with KNK437, both HSP72 and IL-6 mRNA elevations, induced by heat, were suppressed. These findings implicate skeletal muscle as a "heat stress sensor" at physiologically relevant hyperthermia, responding with a programmed cytokine expression pattern characterized by elevated IL-6. PMID- 22673619 TI - Noncompetitive blocking of human GLUT1 hexose transporter by methylxanthines reveals an exofacial regulatory binding site. AB - Glucose transporter (GLUT)1 has become an attractive target to block glucose uptake in malignant cells since most cancer cells overexpress GLUT1 and are sensitive to glucose deprivation. Methylxanthines are natural compounds that inhibit glucose uptake; however, the mechanism of inhibition remains unknown. Here, we used a combination of binding and glucose transport kinetic assays to analyze in detail the effects of caffeine, pentoxifylline, and theophylline on hexose transport in human erythrocytes. The displacement of previously bound cytochalasin B revealed a direct interaction between the methylxanthines and GLUT1. Methylxanthines behave as noncompetitive blockers (inhibition constant values of 2-3 mM) in exchange and zero-trans efflux assays, whereas mixed inhibition with a notable uncompetitive component is observed in zero-trans influx assays (inhibition constant values of 5-12 mM). These results indicate that methylxanthines do not bind to either exofacial or endofacial d-glucose binding sites but instead interact at a different site accessible by the external face of the transporter. Additionally, infinite-cis exit assays (Sen-Widdas assays) showed that only pentoxifylline disturbed d-glucose for binding to the exofacial substrate site. Interestingly, coinhibition assays showed that methylxanthines bind to a common site on the transporter. We concluded that there is a methylxanthine regulatory site on the external surface of the transporter, which is close but distinguishable from the d-glucose external site. Therefore, the methylxanthine moiety may become an attractive framework for the design of novel specific noncompetitive facilitative GLUT inhibitors. PMID- 22673620 TI - Purinergic signaling and immune cell chemotaxis. Focus on "the UDP-sugar-sensing P2Y14 receptor promotes Rho-mediated signaling and chemotaxis in human neutrophils". PMID- 22673621 TI - Identification of atrogin-1-targeted proteins during the myostatin-induced skeletal muscle wasting. AB - Atrogin-1, a muscle-specific E3 ligase, targets MyoD for degradation through the ubiquitin-proteasome-mediated system. Myostatin, a member of the transforming growth factor-beta superfamily, potently inhibits myogenesis by lowering MyoD levels. While atrogin-1 is upregulated by myostatin, it is currently unknown whether atrogin-1 plays a role in mediating myostatin signaling to regulate myogenesis. In this report, we have confirmed that atrogin-1 increasingly interacts with MyoD upon recombinant human myostatin (hMstn) treatment. The absence of atrogin-1, however, led to elevated MyoD levels and permitted the differentiation of atrogin-1(-/-) primary myoblast cultures despite the presence of exogenous myostatin. Furthermore, inactivation of atrogin-1 rescued myoblasts from growth inhibition by hMstn. Therefore, these results highlight the central role of atrogin-1 in regulating myostatin signaling during myogenesis. Currently, there are only two known targets of atrogin-1. Thus, we next characterized the associated proteins of atrogin-1 in control and hMstn-treated C2C12 cell cultures by stably expressing tagged atrogin-1 in myoblasts and myotubes, and sequencing the coimmunoprecipitated proteome. We found that atrogin-1 putatively interacts with sarcomeric proteins, transcriptional factors, metabolic enzymes, components of translation, and spliceosome formation. In addition, we also identified that desmin and vimentin, two components of the intermediate filament in muscle, directly interacted with and were degraded by atrogin-1 in response to hMstn. In summary, the muscle wasting effects of the myostatin-atrogin-1 axis are not only limited to the degradation of MyoD and eukaryotic translation initiation factor 3 subunit f, but also encompass several proteins that are involved in a wide variety of cellular activities in the muscle. PMID- 22673622 TI - The UDP-sugar-sensing P2Y(14) receptor promotes Rho-mediated signaling and chemotaxis in human neutrophils. AB - The G(i)-coupled P2Y(14) receptor (P2Y(14)-R) is potently activated by UDP-sugars and UDP. Although P2Y(14)-R mRNA is prominently expressed in circulating neutrophils, the signaling pathways and functional responses associated with this receptor are undefined. In this study, we illustrate that incubation of isolated human neutrophils with UDP-glucose resulted in cytoskeleton rearrangement, change of cell shape, and enhanced cell migration. We also demonstrate that UDP-glucose promotes rapid, robust, and concentration-dependent activation of RhoA in these cells. Ecto-nucleotidases expressed on neutrophils rapidly hydrolyzed extracellular ATP, but incubation with UDP-glucose for up to 1 h resulted in negligible metabolism of the nucleotide-sugar. HL60 human promyelocytic leukemia cells do not express the P2Y(14)-R, but neutrophil differentiation of HL60 cells with DMSO resulted in markedly enhanced P2Y(14)-R expression. Accordingly, UDP glucose, UDP-galactose, and UDP-N-acetylglucosamine promoted Rho activation in differentiated but not in undifferentiated HL60 cells. Stable expression of recombinant human P2Y(14)-R conferred UDP-sugar-promoted responses to undifferentiated HL60 cells. UDP-glucose-promoted RhoA activation also was accompanied by enhanced cell migration in differentiated HL60 cells, and these responses were blocked by Rho kinase inhibitors. These results support the notion that UDP-glucose is a stable and potent proinflammatory mediator that promotes P2Y(14)-R-mediated neutrophil motility via Rho/Rho kinase activation. PMID- 22673623 TI - Primary pleuropulmonary sarcoma: a rare disease entity. PMID- 22673624 TI - Prophylactic cranial irradiation for patients with limited-stage small-cell lung cancer with response to chemoradiation. AB - BACKGROUND: Previous clinical studies have generally reported that prophylactic cranial irradiation (PCI) was given to patients with a complete response (CR) to chemotherapy and chest radiotherapy in limited-stage small-cell lung cancer (SCLC). It is not clear if those with incomplete response (IR) would benefit from PCI. PATIENTS AND METHODS: The Saskatchewan experience from 1981 through 2007 was reviewed. Patients were treated with chest radiotherapy and chemotherapy with or without PCI (typical doses: 2500 cGy in 10 fractions over 2 weeks, 3000 cGy in 15 fractions over 3 weeks, or 3000 cGy in 10 fractions over 2 weeks). RESULTS: There were 289 patients treated for curative intent, 177/289 (61.2%) of whom received PCI. For the whole group of 289 patients, PCI resulted in significant overall survival (OS) and cause-specific survival (CSS) benefit (P = .0011 and 0.0005, respectively). The time to symptoms of first recurrence at any site with or without PCI was significantly different: 16.9 vs. 13.2 months (P = .0006). PCI significantly delayed the time to symptoms of first recurrence in the brain: 20.7 vs. 10.6 months (P < .0001). The first site of metastasis was the brain for 12.5% and 45.5% patients with CR with and without PCI, respectively (P = .02) and in 6.1% and 27.6% of patients with IR with and without PCI, respectively (P = .05). For the 93 patients with IR, PCI did not confer OS or CSS benefit (P = .32 and 0.39, respectively). CONCLUSIONS: Patients with IR benefited from PCI, with a reduced rate of and a delayed time for the development of brain metastases, although without significant OS or CSS benefit. PCI could be considered for all patients with limited-stage SCLC responding to chemoradiation. PMID- 22673625 TI - Increased prevalence of temporary cardiac pacing in people with epilepsy. AB - INTRODUCTION: Even though ictal tachyarrhythmias are more common, ictal brady asystole is more likely to be fatal, and yet is potentially preventable with pacemaker (PM) implantation. We sought to quantify the degree of association of PM placement in people with and without epilepsy, including neurological and cardiovascular cohorts. METHODS: Retrospective cross-sectional analysis of the National Hospital Discharge database using International Classification of Diseases Clinical Modification (ICD-9-CM) codes. We identified people with and without epilepsy between 1990 and 2006. The epilepsy cohort was compared to patients without epilepsy and other cardiovascular and central nervous system (CNS) disease cohorts. RESULTS: People with epilepsy had higher odds of temporary PM (TPM; OR 1.6) than patients without epilepsy, especially amongst males (OR 2.0), young- (OR 4.6) and middle-aged (OR 4.3) patients. The epilepsy cohort had significantly higher odds of TPM than demyelinating disease (OR 7.9) and migraine (OR 9.1) cohorts. Compared to stroke, people with epilepsy had higher odds of TPM in the male (OR 1.6) and middle-age (OR 2.4) subgroups. No significant association was seen with permanent PM (PPM). CONCLUSIONS: Our study demonstrates the high likelihood of TPM placement in epilepsy patients as compared to cohorts without epilepsy. Significant associations were seen especially in males and young- and middle-aged patients. Since demyelinating and migraine cohorts are somewhat similar to epilepsy patients in age and sex characteristics, the higher odds of TPM in epilepsy patients may be related to the disease mechanism causing brady-asystole; however this requires further study. PMID- 22673626 TI - Influence of geogenic factors on microbial communities in metallogenic Australian soils. AB - Links between microbial community assemblages and geogenic factors were assessed in 187 soil samples collected from four metal-rich provinces across Australia. Field-fresh soils and soils incubated with soluble Au(III) complexes were analysed using three-domain multiplex-terminal restriction fragment length polymorphism, and phylogenetic (PhyloChip) and functional (GeoChip) microarrays. Geogenic factors of soils were determined using lithological-, geomorphological- and soil-mapping combined with analyses of 51 geochemical parameters. Microbial communities differed significantly between landforms, soil horizons, lithologies and also with the occurrence of underlying Au deposits. The strongest responses to these factors, and to amendment with soluble Au(III) complexes, was observed in bacterial communities. PhyloChip analyses revealed a greater abundance and diversity of Alphaproteobacteria (especially Sphingomonas spp.), and Firmicutes (Bacillus spp.) in Au-containing and Au(III)-amended soils. Analyses of potential function (GeoChip) revealed higher abundances of metal-resistance genes in metal rich soils. For example, genes that hybridised with metal-resistance genes copA, chrA and czcA of a prevalent aurophillic bacterium, Cupriavidus metallidurans CH34, occurred only in auriferous soils. These data help establish key links between geogenic factors and the phylogeny and function within soil microbial communities. In particular, the landform, which is a crucial factor in determining soil geochemistry, strongly affected microbial community structures. PMID- 22673628 TI - Regulation of the dissolved phosphate concentration of a mountainous stream, Kitakyushu, southwestern Japan. AB - The phosphate concentration in mountainous stream water can be a measure of the forest condition, because its concentration will be low when the biomass in the forest is increasing and vice versa when the forest is declining. To investigate the seasonal change in the dissolved phosphate concentration of the mountainous stream water of the Yamakami River, Kitakyushu, from June 2009 to August 2010, and the regulation mechanism of the phosphate concentration, solid-phase spectrophotometry, which can be applicable to natural water without any pretreatment procedures, was employed for the determination of phosphate at MUg P L(-1) levels in natural water. The phosphate concentrations in the mountainous stream waters at 6 sites ranged from 2.2 to 13 MUg P L(-1), and those from the catchment area of the steady state forest were 5.3 +/- 1.6 (+/-1 SD) MUg P L(-1). Changes in the concentration were fairly small even during a storm runoff. The average phosphate concentration of rain was 2.8 +/- 0.7 MUg P L(-1), about half of the concentration in the stream water. The rate of runoff in forest areas is generally considered to be about 50% of the total precipitation. For a forest under a climax condition, the phosphate concentration is estimated to be regulated by the fallout and evapotranspiration (alpha = 0.05). At one of the sites, an upstream tributary, where a fairly big landslide occurred before July in 2009, the phosphate concentration was the highest, suggesting that the biomass may still be decreasing. For all of the six sites examined, a characteristic seasonal change in phosphate concentration was observed, reflecting the local budget between the biological decomposition of plant matter and the consumption by the biomass. The increase in the phosphate concentration during late spring and early summer may result from the extensive decomposition of plant litter mainly supplied in autumn and of plant matter relating to spring blooming such as fallen flowers, pollen and immature fruits. The proposed method using the phosphate concentration in surface stream waters without the period of the seasonal change mentioned above is expected to be very helpful in diagnosing the condition of forests. PMID- 22673627 TI - Monitoring of Vibrio harveyi quorum sensing activity in real time during infection of brine shrimp larvae. AB - Quorum sensing, bacterial cell-to-cell communication, has been linked to the virulence of pathogenic bacteria. Indeed, in vitro experiments have shown that many bacterial pathogens regulate the expression of virulence genes by this cell to-cell communication process. Moreover, signal molecules have been detected in samples retrieved from infected hosts and quorum sensing disruption has been reported to result in reduced virulence in different host-pathogen systems. However, data on in vivo quorum sensing activity of pathogens during infection of a host are currently lacking. We previously reported that quorum sensing regulates the virulence of Vibrio harveyi in a standardised model system with gnotobiotic brine shrimp (Artemia franciscana) larvae. Here, we monitored quorum sensing activity in Vibrio harveyi during infection of the shrimp, using bioluminescence as a read-out. We found that wild-type Vibrio harveyi shows a strong increase in quorum sensing activity early during infection. In this respect, the bacteria behave remarkably similar in different larvae, despite the fact that only half of them survive the infection. Interestingly, when expressed per bacterial cell, Vibrio harveyi showed around 200-fold higher maximal quorum sensing-regulated bioluminescence when associated with larvae than in the culture water. Finally, the in vivo quorum sensing activity of mutants defective in the production of one of the three signal molecules is consistent with their virulence, with no detectable in vivo quorum sensing activity in AI-2- and CAI-1 deficient mutants. These results indicate that AI-2 and CAI-1 are the dominant signals during infection of brine shrimp. PMID- 22673629 TI - A low band-gap polymer based on unsubstituted benzo[1,2-b:4,5-b']dithiophene for high performance organic photovoltaics. AB - A low band-gap conjugated polymer, PBDTDPP, composed of unsubstituted benzo[1,2 b:4,5-b']dithiophene and diketopyrrolo[3,4-c]pyrrole was synthesized. The deep HOMO level of PBDTDPP enhances the V(OC) of a PSC up to 0.82 V and exhibits a PCE of 5.16%, while alkoxy substituted PBDTDPP-OR yields a PCE of 2.24% with a V(OC) of 0.61 V. PMID- 22673630 TI - EGFR mutation heterogeneity and the mixed response to EGFR tyrosine kinase inhibitors of lung adenocarcinomas. AB - BACKGROUND: Non-small cell lung cancer patients with epidermal growth factor receptor (EGFR) mutations have mixed responses to tyrosine kinase inhibitors (TKIs). Intertumor heterogeneity in EGFR mutations is one potential explanation for this phenomenon. METHODS: We performed direct sequencing to identify EGFR mutations in 180 pairs of lung adenocarcinoma samples (from 3,071 patients). The high-resolution melting method was used in discordant cases to confirm EGFR mutation status. Matching samples were divided into four groups: primary lesions detected at different times, primary tumors with matched metastatic lymph nodes, multiple pulmonary nodules, and primary tumors with matched distant metastases. Multivariate analyses were performed to evaluate correlations between heterogeneity and patient characteristics. RESULTS: In the study population, the discordance rate was 13.9% (25 of 180). The multiple pulmonary nodules group had the highest discordance rate of 24.4% (10 of 41; odds ratio for heterogeneity in primary lesions detected at different times, 6.37; 95% confidence interval, 1.71 23.72; p = .006). Discordance rates in the metachronous and synchronous settings were 15.7% (22 of 140) and 7.5% (three of 40), respectively. In the 34 patients who developed EGFR TKI resistance, 10 (29.4%) cases exhibited heterogeneity and five (14.7%) patients exhibited a mixed response to the drug. Three (8.8%) of the patients with a mixed response also exhibited discordant EGFR mutations. CONCLUSIONS: The overall discordance rate of EGFR mutation heterogeneity in Asian patients with pulmonary adenocarcinoma is relatively low, but the rate in patients with multiple pulmonary nodules is significantly higher. This observation may explain the mixed tumor response to EGFR TKIs. PMID- 22673631 TI - Administration of angiotensin-converting enzyme inhibitors and beta-blockers during adjuvant trastuzumab chemotherapy for nonmetastatic breast cancer: marker of risk or cardioprotection in the real world? AB - BACKGROUND: Adjuvant trastuzumab therapy improves the outcome of patients with early breast cancer (EBC) and overexpression of human epidermal growth factor receptor 2 (HER2). However, it is potentially cardiotoxic. This study aims to evaluate the relationship between the use of angiotensin-converting enzyme inhibitors/receptor blockers (ACEi/ARBs) and/or beta-blockers and development of heart failure (HF) and/or left ventricular dysfunction during 1 year of adjuvant trastuzumab therapy. METHODS: A total of 499 women receiving adjuvant trastuzumab therapy for EBC entered in a multicenter registry and were divided into four subgroups according to treatment with ACEi/ARBs and/or beta-blockers. Occurrence of HF and decrease of left ventricular ejection fraction (LVEF; minimum 10 percentage points) were recorded. RESULTS: HF occurred in 2% of patients who did not take either ACEi/ARBs or beta-blockers, 8% of patients receiving ACEi/ARBs alone, 8% receiving beta-blockers alone (p = .03), and 19% receiving both medications (p < .01). The prevalence of patients with LVEF that decreased by at least 10 percentage points was similar in all groups. Combined ACEi/ARBs and beta blocker therapy was independently associated with hypertension and a significant reduction of LVEF from baseline to 3-month evaluation. The use of ACEi/ARBs alone or beta-blockers alone was predicted only by hypertension. Combined therapy of ACEi/ARBs plus beta-blockers predicted LVEF recovery from the 3-month to 12-month evaluation. CONCLUSIONS: In clinical practice, the degree of hypertension and decrease in LVEF during the first 3 months of adjuvant trastuzumab therapy for EBC are associated with the use of ACEi/ARBs and beta-blockers. The combined use of these two medications is associated with a recovery of LVEF during months 3-12 of adjuvant trastuzumab therapy. PMID- 22673633 TI - Factors impacting prognosis prediction in BCLC stage C and Child-Pugh class A hepatocellular carcinoma patients in prospective clinical trials of systemic therapy. AB - BACKGROUND: The purpose of this study was to determine the prognostic significance of clinical factors and staging systems for survival of hepatocellular carcinoma (HCC) patients who are candidates for therapeutic clinical trials. METHODS: From December 1990 to July 2005, 236 patients with unresectable HCC were enrolled into six published phase II trials assessing various therapeutic regimens. Of these, 156 chemotherapy-naive patients with Child-Pugh class A and Barcelona Clinic Liver Cancer stage C disease were included in this analysis. Twenty-seven relevant clinical characteristics were analyzed to identify prognostic factors of survival. Beyond these prognosticators, the predictive ability of eight staging systems (the tumor-node metastasis, Okuda, Cancer of the Liver Italian Program [CLIP], Chinese University Prognostic Index, Japanese Integrated Staging, Tokyo, National Taiwan University Risk Estimation, and Advanced Liver Cancer Prognostic System [ALCPS] score) were compared using the Akaike information criteria. RESULTS: The median overall survival time was 129 days (95% confidence interval, 111-147 days). Significant predictors of a shorter overall survival time were an Eastern Cooperative Oncology Group performance status score >=2, the presence of symptoms, ascites, an aspartate transaminase level more than two times the upper limit of normal, and regional lymph node involvement. The ALCPS and CLIP scores were superior to the other systems for predicting survival. CONCLUSIONS: The prognosis of patients with advanced HCC who are candidates for therapeutic clinical trials is affected by several factors related to the patient, liver function, and the tumor. The ALCPS and CLIP scores appear to be superior to the other systems for predicting survival. PMID- 22673632 TI - BRCAness: finding the Achilles heel in ovarian cancer. AB - Ovarian cancer is the leading cause of death among gynecological cancers. It exhibits great heterogeneity in tumor biology and treatment response. Germline mutations of DNA repair genes BRCA1/2 are the fundamental defects in hereditary ovarian cancer that expresses a distinct phenotype of high response rates to platinum agents, improved disease-free intervals and survival rates, and high grade serous histology. The term "BRCAness" describes the phenotypic traits that some sporadic ovarian tumors share with tumors in BRCA1/2 germline mutation carriers and reflects similar causative molecular abnormalities. BRCA pathway studies and molecular profiling reveal BRCA-related defects in almost half of the cases of ovarian cancer. BRCA-like tumors are particularly sensitive to DNA damaging agents (e.g., platinum agents) because of inadequate BRCA-mediated DNA repair mechanisms, such as nucleotide-excision repair and homologous recombination (HR). Additional inhibition of other DNA repair pathways leads to synthetic lethality in HR-deficient cells; this has been employed in the treatment of BRCA-like ovarian tumors with poly(ADP-ribose) polymerase inhibitors with promising results. This article presents a comprehensive review of the relevant literature on the role of BRCAness in ovarian cancer with respect to BRCA function, methods of BRCA epigenetic defect detection and molecular profiling, and the implications of BRCA dysfunction in the treatment of ovarian cancer. PMID- 22673634 TI - Acute aortic dissection with tear in ascending aorta not diagnosed until necropsy or operation (for another condition) and comparison to similar cases receiving proper operative therapy. AB - Acute aortic dissection (AD) with a tear in ascending aorta (AA) is recognized to masquerade occasionally as another condition, and therefore the proper diagnosis is never made or made too late. During a recent 3-year period (2009 to 2011) at Baylor University Medical Center at Dallas, 30 patients with acute AD with tear in AA were diagnosed: 23 (77%) were diagnosed clinically and underwent proper urgent operative therapy; the remaining 7 (23%) with AD with tear in AA were not diagnosed until operation (for another condition) or necropsy or retrospectively by review of antemortem computed tomographic scan after death. The number of patients with AD from tear in AA whose cardiac condition was not diagnosed clinically and who died in the hospital but did not have an autopsy is unclear. Because the autopsy rate in most United States hospitals, including Baylor University Medical Center, is now <5%, many cases of AD are probably not diagnosed and thus its frequency is being underestimated. In conclusion, >= 7 of 30 patients (23%) with acute AD with a tear in AA were not diagnosed until necropsy or operation (for another condition) or retrospectively by computed tomography during a 3-year period at a large tertiary medical center showing that this condition continues to be underdiagnosed, and when not diagnosed correctly is usually rapidly fatal. Because the autopsy rate today is so low, the percentage not diagnosed clinically is probably >23%. PMID- 22673635 TI - Peter Libby, MD: a conversation with the editor. PMID- 22673637 TI - Effect of gamma-oryzanol-enriched rice bran oil on quality of cryopreserved boar semen. AB - The aim of this study was to determine the effect of gamma-oryzanol-enriched rice bran oil on the quality of cryopreserved boar semen. Ten boars provided semen of proven motility and morphology for this study. The semen was divided into three portions in which lactose-egg yolk (LEY) extender used to resuspend the centrifuged sperm pellet was supplemented with 2 types of rice bran oils, at a gamma-oryzanol concentration of 0 mg/ml of lactose egg yolk (LEY) freezing extender (group A, control), 0.1 mg/ml(0.16 mMol) of freezing extender (group B) and 0.1 mg/ml of freezing extender (group C). Semen suspensions were loaded in medium straws (0.5 ml) and placed in a controlled-rate freezer. After cryopreservation, frozen semen samples were thawed and investigated for progressive motility, viability and acrosomal integrity. There was a significantly higher percentage of progressive motility (34 versus 47.0 and 48.5, P<0.001), viability (35.5 versus 48.1 and 50.1, P<0.001) and acrosomal integrity (39.8 versus 50.8 and 54.9, P<0.001) in the gamma-oryzanol-enriched rice bran oil supplemented groups (groups B, C) than in the control group (group C), respectively. In conclusion, addition of gamma-oryzanol-enriched rice bran oil to LEY freezing extender is appropriated for improving the quality of frozen-thawed boar semen. PMID- 22673636 TI - Immune response to influenza A/H1N1 vaccine in inflammatory bowel disease patients treated with anti TNF-alpha agents: effects of combined therapy with immunosuppressants. AB - BACKGROUND AND AIMS: Our first objective was to evaluate the immune response to the adjuvanted 2009 A/H1N1 pandemic (pH1N1) vaccine in inflammatory bowel disease (IBD) patients treated with anti-TNF-alpha alone or combined with immunosuppressants (IS). Second and third aims were the safety of pH1N1 vaccine and the effects on IBD clinical activity. METHODS: 36 patients with Crohn's disease (CD) and 26 with ulcerative colitis (UC) and thirty-one healthy control (HC) subjects were enrolled. 47 patients were on anti TNF-alpha maintenance monotherapy and 15 on anti TNF-alpha combined with IS. Sera were collected at baseline (T0) and 4 weeks after the vaccination (T1) for antibody determination by hemagglutination inhibition (HAI). Disease activity was monitored at T0 and T1. RESULTS: Seroprotective titers (>=1:40) in patients were comparable to HC. Seroconvertion rate (>=4 fold increase in HAI titer) was lower than HC in IBD patients (p=0.009), either on anti TNF-alpha monotherapy (p=0.034) or combined with IS (p=0.011). Geometric mean titer (GMT) of antibodies at T1 was significantly lower in patients on combined therapy versus those on monotherapy (p=0.0017) and versus HC (p=0.011). The factor increase of GMT at T1 versus T0 was significantly lower in IBD patients versus HC (p=0.042), and in those on combined immunosuppression, both versus monotherapy (p=0.0048) and HC (p=0.0015). None of the patients experienced a disease flare. CONCLUSION: Our study has shown a suboptimal response to pH1N1 vaccine in IBD patients on therapy with anti TNF alpha and IS compared to those on anti-TNF-alpha monotherapy and HC. PMID- 22673638 TI - Rapid-air-dry papanicolaou stain in canine and feline tumor cytology: a quantitative comparison with the Giemsa stain. AB - The Papanicolaou stain is a gold-standard staining method for tumor diagnosis in human cytology. However, it has not been used routinely in veterinary cytology, because of its complicated multistep procedure and requirement for wet fixation. Currently, a rapid Papanicolaou stain using air-dried smears is utilized in human cytology, but usefulness of this rapid-air-dry Papanicolaou (RAD-Pap) stain in the veterinary field has not been fully evaluated. The purpose of this study was to evaluate the usefulness of the RAD-Pap stain by using quantitative analysis. Air-dried impression smears were collected from tumor specimens and stained with RAD-Pap and Giemsa. Twelve parameters representing the criteria of malignancy were quantitated, and characteristics of the RAD-Pap were evaluated statistically. The RAD-Pap stain could be applied to all the smears, and images of nucleoli and chromatin patterns were clear and detailed. In quantitative analysis with the RAD-Pap stain, but not with the Giemsa stain, dispersion of nucleolus size and dispersion of nucleolus/nucleus ratio in malignant tumors were significantly higher than those in benign tumors. These findings demonstrated that the RAD-Pap stain was useful for obtaining detailed nuclear information, and the ability to differentiate benignity and malignancy by nucleolus findings was a principal advantage of this stain. This RAD-Pap stain could be routinely used as a supportive staining method in veterinary diagnostic cytology. PMID- 22673639 TI - Involvement of mitochondrial genes of Babesia gibsoni in resistance to diminazene aceturate. AB - The stability of the characteristics of the diminazene aceturate (DA)-resistant B. gibsoni isolate was initially determined in vitro. Part of the DA-resistant B. gibsoni isolate was cultured without DA for 4 weeks, and then newly exposed to 200 ng/ml DA. As a result, this isolate could proliferate the same as the DA resistant isolate, indicating that the characteristic of DA resistance was stable in the DA-resistant isolate. Additionally, the level of parasitemia in the DA resistant isolate was comparatively lower than in the wild-type, suggesting that the proliferation potential of the DA-resistant isolate would be lower than that of the wild-type. Subsequently, to investigate the involvement of mitochondrial DNA (mtDNA) in DA resistance in B. gibsoni, the nucleotide sequences and deduced amino acid sequences of mitochondrial genes such as COXI, COXIII, and CYTb genes of the DA-resistant isolate, were compared with those of the wild-type. As a result, these three genes were not altered in the DA-resistant B. gibsoni isolate. Moreover, the transcription levels of COXI, COXIII, and CYTb genes were observed by semi-quantitative RT-PCR. As a result, the gene transcription of those genes in the DA-resistant isolate was not significantly altered. These results indicated that DA did not affect mtDNA directly in DA-resistant B. gibsoni. Thus, it is suggested that mtDNA should not be deeply involved in DA resistance in B. gibsoni. PMID- 22673640 TI - Leveraging kinase inhibitors to develop small molecule tools for imaging kinases by fluorescence microscopy. AB - As the usage of fluorescence microscopy as a tool to study biological systems continues to grow, so does the need for additional tools that permit the selective detection of proteins of interest. Existing selective and well characterized kinase inhibitors may be exploited to develop novel small molecule probes useful in imaging kinases by fluorescence microscopy. PMID- 22673641 TI - Office work and complaints of the arms, neck and shoulders: the role of job characteristics, muscular tension and need for recovery. AB - OBJECTIVES: This study investigated physical, psychological and social job characteristics as potential risk factors for complaints of the arms, neck and shoulders (CANS) and mediating effects of muscular tension and need for recovery. METHODS: Data were collected among 105 computer workers using questionnaires and electromyography (EMG), and were analyzed with linear regression analyses. RESULTS: Task interdependence, information processing and lower social support predicted more CANS. Physical job demands had no predictive power over and above psychological and social Stressors. Both muscular tension and need for recovery partially mediated the job characteristics-CANS relationships. CONCLUSIONS: Occupational health professionals should not neglect psychological and social job characteristics as potentially important predictors of CANS in specific occupational groups, such as office workers. Our findings imply that CANS interventions should not be restricted to ergonomic improvements, but should be accompanied by improvement of the job design from a psychological and social perspective and reactive intervention aimed at decreasing short-term physical strain (muscular tension) and mental strain (need for recovery). PMID- 22673642 TI - Noise attenuation of earplugs as measured by hREAT and F-MIRE methods in a Japanese metal manufacturing plant. AB - OBJECTIVE: The aim of this study was to compare the noise attenuation (NA) properties of earplugs by using the headphone-based real-ear-attenuation-at threshold (hREAT) and field microphone-in-real-ear (F-MIRE) techniques. METHODS: The subjects were 89 male workers (mean age: 44.8 +/- 12.1 yr) exposed to noise above 85 dBA (mean noise exposure period: 14.3 +/- 11.3 yr) in a Japanese nonferrous metal manufacturing plant. They were confirmed to have pure-tone air conduction hearing threshold levels (HTLs). The hREAT and F-MIRE NA values were measured by a Rion AG-20A and a 3M E-A-Rfit, respectively. RESULTS: The NA values could not be measured by hREAT for four workers (hREAT-group). The mean NA of the earplugs for subjects for whom hREAT measurements were possible (hREAT+ group) was 26.0 +/- 10.0 dB. The NA of the earplugs could be measured for all subjects using F-MIRE, and the NAs of the hREAT- and hREAT+ groups were 9.5 +/- 8.7 and 21.0 +/- 7.3 dB. The mean HTL value at 500 Hz to 2 kHz was 45.8 +/- 3.1 dB for the hREAT- group, which was significantly lower than the value for the hREAT+ group, 18.0 +/- 8.6 dB. CONCLUSION: Because there is a difference between the NA values obtained by hREAT and F-MIRE, it may be necessary to compensate for this difference. In addition, workers with hearing loss and the length of the measurement time need to be taken into consideration. Finally the F-MIRE method may be useful for educating workers about using earplugs in noisy workplaces. PMID- 22673643 TI - Occupational exposure to manganese-containing welding fumes and pulmonary function indices among natural gas transmission pipeline welders. AB - OBJECTIVES: The objectives of this study were to evaluate manganese (Mn) containing welding fumes' exposure, assess urinary Mn as a biomarker for Mn exposure and investigate the correlation of Mn in air, total fumes and urinary Mn with pulmonary function indices in 118 welders and 37 unexposed controls from two regions in Iran, Assaluyeh and Borujen. METHODS: Air samples were collected on mixed cellulose ester membrane filters in personal air samplers and then analyzed using inductively coupled plasma atomic emission spectroscopy (ICP-AES) (NIOSH Method 7300). For all participants, urine samples were collected during the entire work shift, and Mn in urine was determined by graphite furnace atomic absorption spectroscopy according to NIOSH Method 8310. Spirometric measurements were also done for participants. RESULTS: The maximum exposures to airborne Mn and total fumes were 0.304 +/- 0.256 mg/m(3) and 21.52 +/- 9.40 mg/m(3), respectively. The urine Mn levels in the various groups ranged between 0.77 to 7.58 MUg/l. The correlation between airborne Mn and urinary Mn was significant for total whole participants. Some values of spirometric indices were statistically lower in welders rather than controls. CONCLUSIONS: Our results indicate that many welders have been exposed to higher concentrations of Mn containing welding fumes. Urinary Mn can be used as a biomarker for Mn exposure. There were weak inverse correlations between Mn-containing welding fumes and pulmonary function indices, and the inverse correlation between urinary Mn with forced vital capacities (FVC) and forced expiratory volume in 1 s (FEV1) was significant. PMID- 22673644 TI - Measles among healthcare workers in a teaching hospital in central Italy. AB - OBJECTIVES: The aim of this report is to describe a measles cluster involving health-care workers (HWCs) that occurred in a teaching hospital in central Italy during winter 2011 and the efforts made to promptly identify all the susceptible contacts in order to stop, as soon as possible, transmission of the infection within the hospital. METHODS: An epidemiological investigation took place. The immunization status of all the exposed individuals was assessed by personal interviews (history of measles or measles vaccine). Serologie screening for personnel not immune to measles was performed. RESULTS: Four cases of measles infection in HCWs were identified; of the 72 HCWs tested for measles immunity, 50 reported a past history of measles, while 22 underwent serological screening, which showed that all were IgG positive except for one case, which was excluded from duty as recommended. Strict adherence to use of alcohol-based hand rub and rapid implementation of appropriate isolation precautions are essential but insufficient to prevent measles outbreaks in hospital settings. Vaccination is the only reliable protection against nosocomial spread of measles. Therefore, assessing the immunization status of HCW and implementing vaccination strategies are needed in order to virtually set to zero the risk of acquiring and spreading measles in healthcare settings. PMID- 22673645 TI - Effect of reduced illumination on insomnia in office workers. AB - OBJECTIVE: We evaluated the possible effects of reduced illumination in the workplace on insomnia among office workers. METHODS: Seventy-two office workers answered the Athens Insomnia Scale (AIS) in July 2009 (under ordinary illumination, 01 conditions) and July 2010 (under reduced illumination, Rl conditions). The workers were divided into three groups, indoor workers (IWs), semi-outdoor workers (SWs) and outdoor workers (OWs), according to the frequency of working outside of the office because a worker with a high frequency of working outside of the office might rarely be exposed to the lighting condition within an office. The first five items of the AIS (AIS-5) were used to assess sleep difficulties, and the last three items (AIS-3) assessed next-day consequences of sleep or daytime symptoms, which often result from insomnia and/or sleep disorders. RESULTS: Illuminance levels at a height of 1,100 mm from the floor under the Rl conditions (550-490 lux) were significantly lower than under the Ol conditions (750-700 lux). The AIS-5 score of the IWs was significantly increased under the Rl conditions compared with the Ol conditions. There was no difference in AIS-3 scores between conditions for any group. CONCLUSION: Indoor workers hardly went outside of the office and were exposed only to office light during the daytime. Thus, the underexposure to light could have had an impact on insomnia in those individuals. A novel lighting environment is required to optimize work-related levels of light exposure. PMID- 22673646 TI - Effect of EMG-based feedback on posture correction during computer operation. AB - OBJECTIVE: The aim of this study was to investigate the effects of an EMG-based feedback device on the human musculoskeletal system by assessing the kinematics of the lumbar and cervical regions during computer operation. METHODS: Using an EMG device, measurements were collected under four conditions: with feedback from the upper trapezius muscle, from the L4-erector spinae muscles and from both and without feedback (control). During periods of 15 min of computer operation, kinematic data were collected using the Zebris motion analysis system to investigate 14 university employees. RESULTS: Feedback assessment effectively reduced the kinematic changes in the sagittal plane compared with the control (p<0.05). Feedback from the L4 erector spinae reduced the trunk flexion and forward head angles, which were significantly different compared with those under the feedback from the upper trapezius and the control conditions (p<0.05). CONCLUSION: We observed that the use of an EMG-based feedback device was effective in reducing habitual forward head and flexed-relaxed postures during computer operation. Additionally, posture correction from the lumbar region could be a way to reduce forward head posture as well as flexed-relaxed posture. PMID- 22673647 TI - Successional dynamics in the seasonally forced diamond food web. AB - Plankton seasonal succession is a classic example of nonequilibrium community dynamics. Despite the fact that it has been well studied empirically, it lacks a general quantitative theory. Here we investigate a food web model that includes a resource, two phytoplankton, and a shared grazer-the diamond food web-in a seasonal environment. The model produces a number of successional trajectories that have been widely discussed in the context of the verbal Plankton Ecology Group model of succession, such as a spring bloom of a good competitor followed by a grazer-induced clear-water phase, setting the stage for the late-season dominance of a grazer-resistant species. It also predicts a novel, counterintuitive trajectory where the grazer-resistant species has both early- and late-season blooms. The model often generates regular annual cycles but sometimes produces multiyear cycles or chaos, even with identical forcing each year. Parameterizing the model, we show how the successional trajectory depends on nutrient supply and the length of the growing season, two key parameters that vary among water bodies. This model extends nonequilibrium theory to food webs and is a first step toward a quantitative theory of plankton seasonal succession. PMID- 22673648 TI - The evolution of patch selection in stochastic environments. AB - A null model for habitat patch selection in spatially heterogeneous environments is the ideal free distribution (IFD), which assumes individuals have complete knowledge about the environment and can freely disperse. Under equilibrium conditions, the IFD predicts that local population growth rates are zero in all occupied patches, sink patches are unoccupied, and the fraction of the population selecting a patch is proportional to the patch's carrying capacity. Individuals, however, often experience stochastic fluctuations in environmental conditions and cannot respond to these fluctuations instantaneously. An evolutionary stability analysis for fixed patch-selection strategies reveals that environmental uncertainty disrupts the classical IFD predictions: individuals playing the evolutionarily stable strategy may occupy sink patches, local growth rates are negative and typically unequal in all patches, and individuals prefer higher quality patches less than predicted by their carrying capacities. Spatial correlations in environmental fluctuations can enhance or marginalize these trends. The analysis predicts that continually increasing environmental variation first selects for range expansion, then selects for persisting coupled sink populations, and ultimately leads to regional extinction. In contrast, continually increasing habitat degradation first selects for range contraction and may select for persisting coupled sink populations before regional extinction. These results highlight the combined roles of spatial and temporal heterogeneity on the evolution of habitat selection. PMID- 22673649 TI - Local adaptation along smooth ecological gradients causes phylogeographic breaks and phenotypic clustering. AB - Coalescent theory has provided a basis for evolutionary biologists to build sophisticated methods for inferring population history from variation in genetic markers, but these methods leave out a major conceptual cornerstone of modern evolutionary theory: natural selection. I provide the first quantitative analysis of the effects of selection on genealogical patterns in a continuously distributed population in which the selective optimum for a trait linked to the marker varies gradually and continuously across the landscape. Simulations show that relatively weak selection for local adaptation can lead to strong phylogeographic structure, in which highly divergent genealogical groups (i.e., clades) are geographically localized and differentially adapted, and dramatically increased standing variation (e.g., coalescence time) compared to neutral expectations. This pattern becomes more likely with increasing population size and with decreasing dispersal distances, mutation rates, and mutation sizes. Under some conditions, the system alternates between a nearly neutral behavior and a behavior in which highly divergent clades are locally adapted. Natural selection on markers commonly used in phylogeographic studies (such as mitochondrial DNA) presents a major challenge to the inference of biogeographic history but also provides exciting opportunities to study how selection affects both between- and within-species biodiversity. PMID- 22673650 TI - Niche specialization influences adaptive phenotypic plasticity in the threespine stickleback. AB - Phenotypic plasticity may be favored in generalist populations if it increases niche width, even in temporally constant environments. Phenotypic plasticity can increase the frequency of extreme phenotypes in a population and thus allow it to make use of a wide resource spectrum. Here we test the prediction that generalist populations should be more plastic than specialists. In a common-garden experiment, we show that solitary, generalist populations of threespine sticklebacks inhabiting small coastal lakes of British Columbia have a higher degree of morphological plasticity than the more specialized sympatric limnetic and benthic species. The ancestral marine stickleback showed low levels of plasticity similar to those of sympatric sticklebacks, implying that the greater plasticity of the generalist population has evolved recently. Measurements of wild populations show that those with mean trait values intermediate between the benthic and limnetic values indeed have higher morphological variation. Our data indicate that plasticity can evolve rapidly after colonization of a new environment in response to changing niche use. PMID- 22673651 TI - Plant preference for ammonium versus nitrate: a neglected determinant of ecosystem functioning? AB - Although nitrogen (N) availability is a major determinant of ecosystem properties, little is known about the ecological importance of plants' preference for ammonium versus nitrate (beta) for ecosystem functioning and the structure of communities. We modeled this preference for two contrasting ecosystems and showed that beta significantly affects ecosystem properties such as biomass, productivity, and N losses. A particular intermediate value of beta maximizes the primary productivity and minimizes mineral N losses. In addition, contrasting beta values between two plant types allow their coexistence, and the ability of one type to control nitrification modifies the patterns of coexistence with the other. We also show that species replacement dynamics do not lead to the minimization of the total mineral N pool nor the maximization of plant productivity, and consequently do not respect Tilman's R* rule. Our results strongly suggest in the two contrasted ecosystems that beta has important consequences for ecosystem functioning and plant community structure. PMID- 22673652 TI - Do animals living in larger groups experience greater parasitism? A meta analysis. AB - Parasitism is widely viewed as the primary cost of sociality and a constraint on group size, yet studies report varied associations between group size and parasitism. Using the largest database of its kind, we performed a meta-analysis of 69 studies of the relationship between group size and parasite risk, as measured by parasitism and immune defenses. We predicted a positive correlation between group size and parasitism with organisms that show contagious and environmental transmission and a negative correlation for searching parasites, parasitoids, and possibly vector-borne parasites (on the basis of the encounter dilution effect). Overall, we found a positive effect of group size (r = 0.187) that varied in magnitude across transmission modes and measures of parasite risk, with only weak indications of publication bias. Among different groups of hosts, we found a stronger relationship between group size and parasite risk in birds than in mammals, which may be driven by ecological and social factors. A metaregression showed that effect sizes increased with maximum group size. Phylogenetic meta-analyses revealed no evidence for phylogenetic signal in the strength of the group size-parasitism relationship. We conclude that group size is a weak predictor of parasite risk except in species that live in large aggregations, such as colonial birds, in which effect sizes are larger. PMID- 22673653 TI - Did pollination shifts drive diversification in southern African Gladiolus? Evaluating the model of pollinator-driven speciation. AB - The pollinator-driven ecological speciation model has frequently been invoked to explain plant richness in biodiversity hotspots. Here, by focusing on Gladiolus (260 species), a flagship example of a clade with diverse pollination biology, we test the hypothesis that high species diversity in southern Africa, one of the world's most floristically rich regions, has primarily been driven by ecological shifts in pollination systems. We use phylogenetic methods to estimate rates of transition between the seven highly specialized pollination strategies in Gladiolus. We find that pollination systems have evolved multiple times and that some pollination strategies arose by a variety of evolutionary pathways. Pollination shifts account for up to one-third of all lineage splitting events in the genus, providing partial support for the pollinator-driven speciation model. Transitions from the ancestral pollination mode to derived systems have also resulted in increased rates of diversification, suggesting that certain pollination systems may speed up speciation processes, independently of pollination shifts per se. This study suggests that frequent pollination shifts have played a role in driving high phenotypic and species diversity but indicates that additional factors need to be invoked to account for the spectacular diversification in southern African Gladiolus. PMID- 22673654 TI - Changing seascapes, stochastic connectivity, and marine metapopulation dynamics. AB - The probability of dispersal from one habitat patch to another is a key quantity in our efforts to understand and predict the dynamics of natural populations. Unfortunately, an often overlooked property of this potential connectivity is that it may change with time. In the marine realm, transient landscape features, such as mesoscale eddies and alongshore jets, produce potential connectivity that is highly variable in time. We assess the impact of this temporal variability by comparing simulations of nearshore metapopulation dynamics when potential connectivity is constant through time (i.e., when it is deterministic) and when it varies in time (i.e., when it is stochastic). We use mathematical analysis to reach general conclusions and realistic biophysical modeling to determine the actual magnitude of these changes for a specific system: nearshore marine species in the Southern California Bight. We find that in general the temporal variability of potential connectivity affects two important quantities: metapopulation growth rates when the species is rare and equilibrium abundances. Our biophysical models reveal that stochastic outcomes are almost always lower than their deterministic counterparts, sometimes by up to 40%. This has implications for how we use spatial information, such as connectivity, to manage nearshore (and other) systems. PMID- 22673655 TI - Genetic effects on mating success and partner choice in a social mammal. AB - Mating behavior has profound consequences for two phenomena--individual reproductive success and the maintenance of species boundaries--that contribute to evolutionary processes. Studies of mating behavior in relation to individual reproductive success are common in many species, but studies of mating behavior in relation to genetic variation and species boundaries are less commonly conducted in socially complex species. Here we leveraged extensive observations of a wild yellow baboon (Papio cynocephalus) population that has experienced recent gene flow from a close sister taxon, the anubis baboon (Papio anubis), to examine how admixture-related genetic background affects mating behavior. We identified novel effects of genetic background on mating patterns, including an advantage accruing to anubis-like males and assortative mating among both yellow like and anubis-like pairs. These genetic effects acted alongside social dominance rank, inbreeding avoidance, and age to produce highly nonrandom mating patterns. Our results suggest that this population may be undergoing admixture related evolutionary change, driven in part by nonrandom mating. However, the strength of the genetic effect is mediated by behavioral plasticity and social interactions, emphasizing the strong influence of social context on mating behavior in socially complex species. PMID- 22673656 TI - Capital breeding and allocation to life-history demands are highly plastic in lizards. AB - The use of stored resources to fuel reproduction, growth, and self-maintenance in the face of uncertain nutrient availability is a tactic common to many organisms. The degree to which organisms rely on stored resources in response to varied nutrients, however, is not well quantified. In this study, we used stable isotope methods to quantify the use of stored versus incoming nutrients to fuel growth and egg and fat body development in lizards under differing nutrient regimes. We found that the degree of capital breeding is a function of an individual's body condition. Furthermore, given sufficient income, lizards in poor condition can allocate simultaneously to storage, growth, and reproduction and "catch up" in body size and reproductive allocation to better-conditioned animals. Using natural variation in the delta(13)C of environmental nutrient pulses, we also found a high degree of variation in capital breeding in a lizard community. These findings demonstrate that capital breeding in lizards is not simply a one-way flow of endogenous stores to eggs but is a function of the condition state of individuals and seasonal nutrient availability. We use our findings to comment on capital breeding in lizards and the utility of the capital-income concept in general. PMID- 22673657 TI - Birds and anthropogenic noise: singing higher may matter. AB - In a recent theoretical study, Nemeth and Brumm explored the effect of amplitude and frequency variation in birdsongs on signal transmission in forested and noisy urban environments. They argued that "increased song pitch might not be an adaptation" but "an epiphenomenon of urbanization." Here we address the validity of comparing the communication benefits of changes in amplitude and frequency to question the adaptive significance of "urban songs." We believe that their calculations actually confirm considerable high-frequency benefits under noisy urban conditions, between and within species. Hence, we conclude that noise dependent frequency shifts in urban birds can be adaptive. PMID- 22673659 TI - Revisiting the ants of Melanesia and the taxon cycle: historical and human mediated invasions of a tropical archipelago. AB - Understanding the historical evolution of biotas and the dynamics of contemporary human-mediated species introductions are two central tasks of biology. One hypothesis may address both-the taxon cycle. Taxon cycles are phases of range expansion and contraction coupled to ecological and evolutionary niche shifts. These historical invasion processes resemble human-mediated invasions in pattern and possibly mechanism, but both the existence of historical cycles and the roles of recent introductions are in question. We return to the system that originally inspired the taxon cycle-Melanesian ants-and perform novel tests of the hypothesis. We analyze (i) the habitat distributions of Fiji's entire ant fauna (183 species), (ii) ecological shifts associated with the in situ radiation of Fijian Pheidole in a phylogenetic context, and (iii) the ecological structure of a massive exotic ant invasion of the archipelago. Our analyses indicate lineages shift toward primary habitats, higher elevation, rarity, and ecological specialization with increasing level of endemism, consistent with taxon cycle predictions. The marginal habitats that historically formed a dispersal conduit in the Pacific are now mostly replaced by human-modified habitats dominated by a colonization pulse of exotic species. We propose this may represent the first phase of an incipient global cycle of human-mediated colonization, ecological shifts, and diversification. PMID- 22673660 TI - The contribution of rare species to community phylogenetic diversity across a global network of forest plots. AB - Niche differentiation has been proposed as an explanation for rarity in species assemblages. To test this hypothesis requires quantifying the ecological similarity of species. This similarity can potentially be estimated by using phylogenetic relatedness. In this study, we predicted that if niche differentiation does explain the co-occurrence of rare and common species, then rare species should contribute greatly to the overall community phylogenetic diversity (PD), abundance will have phylogenetic signal, and common and rare species will be phylogenetically dissimilar. We tested these predictions by developing a novel method that integrates species rank abundance distributions with phylogenetic trees and trend analyses, to examine the relative contribution of individual species to the overall community PD. We then supplement this approach with analyses of phylogenetic signal in abundances and measures of phylogenetic similarity within and between rare and common species groups. We applied this analytical approach to 15 long-term temperate and tropical forest dynamics plots from around the world. We show that the niche differentiation hypothesis is supported in six of the nine gap-dominated forests but is rejected in the six disturbance-dominated and three gap-dominated forests. We also show that the three metrics utilized in this study each provide unique but corroborating information regarding the phylogenetic distribution of rarity in communities. PMID- 22673661 TI - Corticosterone predicts foraging behavior and parental care in macaroni penguins. AB - Corticosterone has received considerable attention as the principal hormonal mediator of allostasis or physiological stress in wild animals. More recently, it has also been implicated in the regulation of parental care in breeding birds, particularly with respect to individual variation in foraging behavior and provisioning effort. There is also evidence that prolactin can work either inversely or additively with corticosterone to achieve this. Here we test the hypothesis that endogenous corticosterone plays a key physiological role in the control of foraging behavior and parental care, using a combination of exogenous corticosterone treatment, time-depth telemetry, and physiological sampling of female macaroni penguins (Eudyptes chrysolophus) during the brood-guard period of chick rearing, while simultaneously monitoring patterns of prolactin secretion. Plasma corticosterone levels were significantly higher in females given exogenous implants relative to those receiving sham implants. Increased corticosterone levels were associated with significantly higher levels of foraging and diving activity and greater mass gain in implanted females. Elevated plasma corticosterone was also associated with an apparent fitness benefit in the form of increased chick mass. Plasma prolactin levels did not correlate with corticosterone levels at any time, nor was prolactin correlated with any measure of foraging behavior or parental care. Our results provide support for the corticosterone-adaptation hypothesis, which predicts that higher corticosterone levels support increased foraging activity and parental effort. PMID- 22673662 TI - The health benefits of blackcurrants. AB - The blackcurrant (Ribes nigrum L., Grossulariceae), a small, perennial shrub native to central Europe and northern Asia, is cultivated throughout the world, including the United States. In addition to its anecdotal use in traditional herbal medicine, modern laboratories have demonstrated the potent anti inflammatory, antioxidant and antimicrobial effects of blackcurrant constituents on a myriad of disease states. The properties of the blackcurrants are conferred from its biochemical constituents, some of which include anthocyans (specifically delphinidin-3-O-glucoside, delphinidin-3-O-rutinoside, cyanidin-3-O-glucoside and cyanidin-3-O-rutinoside), flavonols, phenolic acids and polyunsaturated fatty acids. A plethora of studies have been published with regards to its various therapeutic applications. This article attempts to summarize these studies, providing a general overview of the research in this field. Several studies focus on the therapeutic potential of blackcurrants with regards to hypertension and other cardiovascular-associated illnesses, neoplastic, neurodegenerative and ocular diseases, nephrolithiasis, and diabetic neuropathy. Safety concerns and future directions are also mentioned, suggesting the critical examination of the exact mechanism of action, specific radical-scavenging capabilities of the blackcurrants and the crucial need for well-designed clinical trials to ensure the successful use of blackcurrants in a clinical setting. PMID- 22673686 TI - Gender-specific association of TSNAX/DISC1 locus for schizophrenia and bipolar affective disorder in South Indian population. AB - Genetic association studies have implicated the TSNAX/DISC1 (disrupted in schizophrenia 1) in schizophrenia (SCZ), bipolar affective disorder (BPAD) and major depression. This study was performed to assess the possible involvement of TSNAX/DISC1 locus in the aetiology of BPAD and SCZ in the Southern Indian population. We genotyped seven single nucleotide polymorphism (SNPs) from TSNAX/DISC1 region in 1252 individuals (419 BPAD patients, 408 SCZ patients and 425 controls). Binary logistic regression revealed a nominal association for rs821616 in DISC1 for BPAD and also combined cases of BPAD or SCZ, but after correcting for multiple testing, these results were non-significant. However, significant association was observed with BPAD, as well as combined cases of BPAD or SCZ, within the female subjects for the rs766288 after applying false discovery rate corrections at the 0.05 level. Two-locus analysis showed C-C (rs766288-rs2812393) as a risk combination in BPAD, and G-T (rs2812393-rs821616) as a protective combination in SCZ and combined cases of BPAD or SCZ. Female specific associations were observed for rs766288-rs2812393, rs766288-rs821616 and rs8212393-rs821616 in two-locus analysis. Our results provide further evidence for sex-dependent effects of the TSNAX/DISC1 locus in the aetiology of SCZ and BPAD. PMID- 22673687 TI - 'Early Neolithic' graves of the Carpathian Basin are in fact 6000 years younger appeal for real interdisciplinarity between archaeology and ancient DNA research. PMID- 22673688 TI - Mitochondrial haplogroup C in ancient mitochondrial DNA from Ukraine extends the presence of East Eurasian genetic lineages in Neolithic Central and Eastern Europe. AB - Recent studies of ancient mitochondrial DNA (mtDNA) lineages have revealed the presence of East Eurasian mtDNA haplogroups in the Central European Neolithic. Here we report the finding of East Eurasian lineages in ancient mtDNA from two Neolithic cemeteries of the North Pontic Region (NPR) in Ukraine. In our study, comprehensive haplotyping information was obtained for 7 out of 18 specimens. Although the majority of identified mtDNA haplogroups belonged to the traditional West Eurasian lineages of H and U, three specimens were determined to belong to the lineages of mtDNA haplogroup C. This find extends the presence of East Eurasian lineages in Neolithic Europe from the Carpathian Mountains to the northern shores of the Black Sea and provides the first genetic account of Neolithic mtDNA lineages from the NPR. PMID- 22673690 TI - Efficient typing of copy number variations in a segmental duplication-mediated rearrangement hotspot using multiplex competitive amplification. AB - Local genomic architecture, such as segmental duplications (SDs), can induce copy number variations (CNVs) hotspots in the human genome, many of which manifest as genomic disorders. Significant technological advances have been achieved for genome-wide CNV investigations, but these costly methods are not suitable for genotyping certain disease-associated CNVs or other loci of interest in populations. Recently, two independent studies showed that the murine meiosis expressed gene 1 (Meig1) was critical to spermatogenesis. We found that the human orthologue MEIG1 is flanked by an SD pair, between which non-allelic homologous recombination (NAHR) can cause recurrent CNVs. To study this potential CNV hotspot and its role in spermatogenesis, we developed a new CNV genotyping method, AccuCopy, based on multiplex competitive amplification to investigate 320 patients with spermatogenic impairment and 93 healthy controls. Three MEIG1 duplications (two in patients and one in controls) were identified, whereas no deletion was found. As NAHR results in more recurrent deletions than duplications at a locus, the over representation of recurrent MEIG1 duplications suggests a potential purifying selection operating on this hotspot, possibly via fecundity. We also showed that AccuCopy is an efficient and reliable method for multiplex CNV genotyping. PMID- 22673691 TI - miRNAs--pathway engineering of CHO cell factories that avoids translational burdening. PMID- 22673692 TI - Colloidal systems for drug delivery: from design to therapy. AB - Nanomedicine, or medicine using nanometric devices, has emerged in the past decade as an exhilarating domain that can help to solve a number of problems linked to unsatisfactory therapeutic responses of so-called 'old drugs'. This dissatisfaction stems from inadequate biodistribution after a drug's application, which leads to a limited therapeutic response but also to numerous side effects to healthy organs. The biodistribution of drugs encapsulated in a nano object that will act as a vector can be modified to tune its therapeutic efficacy. This review provides a general overview of existing colloidal nanovectors: liposomes, polymeric micelles, polymeric vesicles, polymeric nanoparticles (NPs), and dendrimers. We describe their characteristics, advantages and drawbacks, and discuss their use in the treatment of various diseases. PMID- 22673693 TI - Optimizing financial incentives to improve health among military personnel: differences by pay grade and across branches. PMID- 22673694 TI - Does the patient-centred medical home work? A critical synthesis of research on patient-centred medical homes and patient-related outcomes. AB - Health-care systems in the USA and most of western Europe face challenges in the coordination and integration of care for patients, particularly those with chronic conditions. In response to these problems, interest in the patient centred medical home (PCMH) model has increased significantly in recent years in the USA, with PCMH implementation underway in a wide variety of practice settings across the country. Despite this enthusiasm, there have been relatively few attempts to examine the empirical evidence on the effects of PCMH on quality and access-related outcomes for patients. This article reviews findings from empirical evaluations of the effects of PCMH on patient-related outcomes and critically examines methodological and conceptual issues in the growing body of PCMH literature. The results of this review suggest that published evaluations are predominantly weighted towards findings that indicate that PCMH is associated with a wide range of positive patient outcomes. However, methodological and measurement issues present in much of this research should be considered when evaluating these findings. The article concludes with recommendations for future PCMH evaluation. PMID- 22673695 TI - Physician attitudes towards chronic disease management in the USA. AB - Whereas physician support of disease management (DM) is recognized as important for improving the quality and effectiveness of care of individuals with chronic illness, little is known about physicians' perceptions of the model or their likelihood of adoption. A multivariate regression analysis was conducted of a 2008 nationally representative sample of practising physicians in the USA who had been exposed to DM programmes (n = 1615) to determine their support for DM and how attitudes differ across physicians. Results indicated that the majority of physicians believe in the quality enhancing benefits of DM programmes, but there are systematic differences in the attitudes towards DM of different types of physicians. Physicians affiliated with health maintenance organizations (HMOs) and hospital-based practices are more likely than other physicians to agree that DM programmes improve their ability to provide high-quality care to patients with chronic conditions. Minority physicians and physicians who perceive their market as more competitive, have a more positive attitude towards DM than white physicians and physicians in less competitive markets. International medical graduates hold relatively positive attitudes about the benefits of DM programmes and older physicians are more likely than their young peers to approve of DM and physicians. Physicians with a higher percentage of patients with chronic conditions are more likely to have a favourable view of DM. Specialty physicians are more likely to have a positive view of DM, and DM-exposed physicians are more likely to perceive that DM programmes lead to improved quality of care. Future study is needed to determine the reasons for these differences in attitudes and whether they can be modified by targeted information. PMID- 22673696 TI - Relationships of hospital-based emergency department culture to work satisfaction and intent to leave of emergency physicians and nurses. AB - Given the limited studies on emergency care management, this study aimed to explore the relationships of emergency department (ED) culture values to certain dimensions of ED physicians' and nurses' work satisfaction and intent to leave. Four hundred and forty-two emergency medical professionals completed the employee satisfaction questionnaire across 119 hospital-based EDs, which had culture value evaluations filed, were used as unit of analysis in this study. Adjusting the personal and employment backgrounds, and the surrounded EDs' unit characteristics and environmental factors, multiple regression analyses revealed that clan and market cultures were related to emergency physicians' work satisfaction and intent to leave. On the other hand, adhocracy, market and hierarchical cultures were related to emergency nurses' work satisfaction. There do exist different patterns among various culture types on various work satisfaction dimensions and intent to leave of emergency physicians and nurses. The findings could offer hospital and ED leaders insights for changes or for building a better atmosphere to enhance the work life of emergency physicians and nurses. PMID- 22673697 TI - Competency assessment and development among health-care leaders: results of a cross-sectional survey. AB - In light of the challenges involved in leading a health care organization, it is important that the executives and managers charged with doing so are competent in a variety of areas. However, leading at all organizational levels does not necessarily require the same levels and types of competencies. The purpose of this research is to determine how well competency training works in health care organizations, and to obtain a better understanding of the competencies needed for leaders at different points of their careers and at various organizational levels. Ten health care management competency domains thought to positively influence job performance for health care executives are presented. The study seeks to answer four hypotheses related to self-perceptions of competencies and training opportunities at various hierarchical levels. A survey method was used to sample a subset of the healthcare executive population in the USA, based on three variables of interest, competency training opportunities, self-reported level of competency and hierarchical level. A series of Kruskal-Wallis and Mann Whitney U tests were conducted to identify perceived differences in both competency level and training opportunities among respondents of various hierarchical levels. The most significant result of our research is that competency training is effective in health care organizations. The implications and need for additional research are discussed. PMID- 22673698 TI - Assessing governance theory and practice in health-care organizations: a survey of UK hospices. AB - This paper sets out a theoretical framework for analyzing board governance, and describes an empirical study of corporate governance practices in a subset of non profit organizations (hospices in the UK). It examines how practices in hospice governance compare with what is known about effective board working. We found that key strengths of hospice boards included a strong focus on the mission and the finances of the organizations, and common weaknesses included a lack of involvement in strategic matters and a lack of confidence, and some nervousness about challenging the organization on the quality of clinical care. Finally, the paper offers suggestions for theoretical development particularly in relation to board governance in non-profit organizations. It develops an engagement theory for boards which comprises a triadic proposition of high challenge, high support and strong grip. PMID- 22673699 TI - Estimating the length of waits: a description of the period lifetable method and comparison with census and event based methods. AB - To discover whether the period lifetable provides more valid estimates of length of wait in prospect than are obtained using the lengths either of (current) waits captured at the time of the mid-period census or of the (prior) waits of those extracted over a specified period. We determined whether there was a surplus (or a deficiency) of extractions within the cross-classification of cohort and waiting time category which straddled each census. We used census-, event- and lifetable-based methods to produce three period-specific estimates of the percentage of waits of 0-2 months, and we determined whether length of wait grew shorter (or longer) from one period to the next. We used Lambda B to indicate the extent to which we were able to predict the direction of change in length of wait once we knew the direction of change in size of list. We found a direct correlation between change in length of wait and change in size of list, as expected under the stock-flow model, when length of wait was estimated using the lifetable for the period (L(B) = 58.33, 95% confidence interval [CI] = 29-88), but we obtained a null correlation when we used census-based estimates (L(B) = 6.45) and we obtained an inverse correlation when we used event-based estimates (L(B) = 57.14, 95% CI = 31-83). The period lifetable appears to provide more valid estimates of length of wait and should therefore be substituted for census- and event-based methods of estimation, wherever possible. PMID- 22673700 TI - Briefing: cross border care. PMID- 22673701 TI - Bilateral ovarian cysts originating from rete ovarii in an African green monkey (Cercopithecus aethiops). AB - Ovarian cyst is common incidental finding in humans and many animals and includes follicular cysts, cystic rete ovarii and mesonephric duct cysts. Ovarian cyst is often associated with reproductive disorders in humans and animals. We found accidentally bilateral cystic masses in ovaries in an African green monkey. Grossly, the left and right ovarian cystic masses were single unilocular cystic structures measuring 0.6 and 1.8 cm in diameter, respectively. Histologically, both cysts were thin-walled structures that arose from the center of the ovary and displaced ovarian tissue peripherally. The cysts were lined by a single layer of nonciliated low cuboidal epithelium. Immunohistochemically, epithelial cells in the cysts were positive for cytokeratin, and the stromal cells were positive for smooth muscle actin but negative for vimentin. These results suggest that these ovarian cysts in an African green monkey are cystic rete ovarii. To our knowledge, this is the first report of cystic rete ovarii in African green monkeys and may be of value in relation to research of the pathogenesis and treatment of ovarian cyst. PMID- 22673702 TI - Characteristics of esophageal diverticula using computed tomography and three dimensional reconstruction in a Maltese dog. AB - A 7-year-old intact female Maltese dog was referred with ptyalism and intermittent vomiting but no regurgitation for over 1 month. Survey radiographs including a contrast study revealed a large circular dilated cavity from the carina to the diaphragm. Additionally, multi-detector computed tomography and three-dimensional reconstruction were performed. These images revealed large idiopathic distal esophageal diverticula. This case report represents the first report using multi-detector computed tomography and three-dimensional reconstruction for evaluation of esophageal diverticula in a dog. PMID- 22673703 TI - Development of a diagnostic method applicable to various serotypes of hantavirus infection in rodents. AB - Antigenic diversity among different hantaviruses requires a variety of reagents for diagnosis of hantavirus infection. To develop a diagnostic method applicable to various hantavirus infections with a single set of reagents, we developed an enzyme-linked immunosorbent assay (ELISA) using recombinant nucleocapsid proteins of three hantaviruses, Amur, Hokkaido, and Sin Nombre viruses. This novel cocktail antigen-based ELISA enabled detection of antibodies against Hantaan, Seoul, Amur, Puumala, and Sin Nombre viruses in immunized laboratory animals. In wild rodent species, including Apodemus, Rattus, and Myodes, our ELISA detected antibodies against hantaviruses with high sensitivity and specificity. These data suggest that our novel diagnostic ELISA is a useful tool for screening hantavirus infections and could be effectively utilized for serological surveillance and quarantine purposes. PMID- 22673704 TI - Endorectal magnetic resonance imaging for predicting pathologic T3 disease in Gleason score 7 prostate cancer: implications for prostate brachytherapy. AB - PURPOSE: To determine the ability of endorectal magnetic resonance imaging (erMRI) and other pretreatment factors to predict the presence and extent of extraprostatic extension (EPE) in men with Gleason score (GS) 7 prostate cancer. METHODS AND MATERIALS: We included patients with clinical stage T1c-T2c, GS=7 (3+4 or 4+3), and prostate-specific antigen (PSA) <10ng/mL who underwent pre prostatectomy erMRI. We compared pathologic EPE findings with pretreatment factors. RESULTS: One hundred seventy-one men were eligible for inclusion. Pretreatment characteristics were: median age=60 years (42-76); median PSA 4.9ng/mL (0.4-9.9); GS 3+4=61%; T1c=51%; T2a=25%; T2b=21%; T2c=3%; >=50% positive cores=46%; EPE-positive (EPE+) erMRI=28%. Thirty-three percent had pathologic EPE. Increasing T-stage (p<0.0001) and EPE+ erMRI (p<0.0001) were significant predictors of pathologic EPE, whereas GS (4+3 vs. 3+4) (p=0.14), percentage of positive core biopsies (p=0.15), and pretreatment PSA (p=0.41) were not. Median EPE distance was 1.75mm (range, <1-15mm). The rates of EPE >5mm and EPE >3mm were 11% and 15%, respectively. The odds ratios for erMRI detection of any EPE and of EPE >5mm were 3.06 and 3.75, respectively. CONCLUSIONS: T-stage and EPE+ erMRI predict pathologic EPE in men with GS 7 prostate cancer. The ability of erMRI to detect EPE increases with increasing EPE distance. These findings may be useful in patient selection for prostate brachytherapy monotherapy. PMID- 22673705 TI - Lifestyle illicit drug seizures: a routine ESI-LC-MS method for the identification of sildenafil and vardenafil. AB - For street samples suspected of containing the phosphodiesterase-5 inhibitors sildenafil (Viagra((r))) and/or vardenafil (Levitra((r))), including powders or adulterated herbal supplements, a chemical analysis is needed to provide confirmatory identification of these illegally procured substances. Sildenafil and vardenafil are structurally similar and it is difficult to differentiate between them, as previous mass spectrometric studies have shown the two drugs to produce similar fragmentation patterns. The use of tandem mass spectrometry can produce confirmatory data, but the technique requires a high level of technical expertise. We have developed an electrospray ionization-liquid chromatography mass spectrometry (ESI-LC-MS) method that allows differentiation between these two structurally similar molecules via in-source fragmentation in combination with an ion trap mass spectrometer. A very stable gas phase ion is formed during in-source fragmentation of vardenafil; the combination of the stability of this ion and the longer residence time for the ion in the ion trap results in a very strong signal. This feature results in a method that can provide clear differentiation between sildenafil and vardenafil while at the same time requiring less expertise from the routine analyst to confirm the presence or absence of the two compounds. PMID- 22673706 TI - Sudden death as a late sequel of Kawasaki disease: postmortem CT demonstration of coronary artery aneurysm. AB - Kawasaki disease (KD) is an acute, self-limited vasculitis of unknown etiology that primarily affects the coronary artery (CA) and presents during childhood. The characteristic coronary arterial lesion of KD is an aneurysm. Ischemic heart disease derived from a CA aneurysm is experienced approximately two decades after the onset of acute KD. In recent years, the primary issue of concern has been asymptomatic adults with a CA aneurysm caused by undiagnosed KD. We present a case of sudden death as a late KD sequel in a young adult. A postmortem CT scan revealed a coarse calcification of a left anterior descending CA aneurysm, which was confirmed at the time of autopsy. A postmortem CT scan is useful in cases of sudden death where the detection of a calcified CA aneurysm would suggest to the forensic pathologist that the deceased suffered from a late sequel of KD. The use of screening postmortem CT scans for young people may detect cases of unsuspected CA aneurysms, raising the possibility of untreated KD. PMID- 22673707 TI - Concentrations of zolpidem and zopiclone in venous blood samples from impaired drivers compared with femoral blood from forensic autopsies. AB - The concentrations of zolpidem and zopiclone were determined in peripheral blood samples in two forensic materials collected over a 10-year period (2001-2010). The z-hypnotics were determined in venous blood from living subjects (impaired drivers) and in femoral blood from deceased persons (forensic autopsies), with the latter classified as intoxication or other causes of death. The z-hypnotics were determined in blood by capillary column gas chromatography (GC) with a nitrogen-phosphorous (N-P) detector after solvent extraction with n-butyl acetate. The analytical limit of quantitation (LOQ) was 0.02 mg/L for zopiclone and 0.05 mg/L for zolpidem and these have remained unchanged throughout the study. When death was attributed to drug intoxication (N=918), the median concentration of zopiclone in blood was 0.20 mg/L compared with 0.06 mg/L for other causes of death (N=1215) and 0.07 mg/L in traffic offenders (N=691) (p<0.001). Likewise, a higher median concentration (0.30 mg/L) was found in intoxication deaths involving zolpidem (N=357) compared with 0.13 mg/L for other causes of death (N=397) or 0.19 mg/L in impaired drivers (N=837) (p<0.001). Median concentration in blood of both z-hypnotics were appreciably higher in intoxication deaths when no other substances were identified; 0 70 mg/L (N=12) for zopiclone and 1.35 mg/L (N=12) for zolpidem. The median concentrations of z hypnotics in blood decreased as the number of co-ingested substances increased for intoxication deaths but not other causes of death. The most prevalent co ingested substances were ethanol in autopsy cases and diazepam in the motorists. This large compilation of forensic cases should prove useful when toxicologists are required to interpret concentrations of z-hypnotics in blood samples in relation to cause of death. PMID- 22673708 TI - A novel D-A-pi-A organic sensitizer containing a diketopyrrolopyrrole unit with a branched alkyl chain for highly efficient and stable dye-sensitized solar cells. AB - A novel D-A-pi-A type organic dye (YCD01) incorporating a diketopyrrolopyrrole unit with a branched alkyl chain was synthesized for dye-sensitized solar cells. YCD01 showed a high conversion efficiency of 7.43% (AM 1.5, 100 mW cm(-2)) with a J(sc) of 13.40 mA cm(-2), a V(oc) of 0.76 V, a FF of 0.73 and an excellent stability. PMID- 22673709 TI - Enhancement of Bronsted acidity in zeolitic catalysts due to an intermolecular solvent effect in confined micropores. AB - Solid-state NMR and DFT calculation studies certified the presence of an intermolecular solvent effect for molecules confined in microporous zeolite, leading to a notable increase in Bronsted acidity of the solid acid catalyst. PMID- 22673710 TI - Pituitary involvement in Wegener's granulomatosis: unusual biochemical findings and severe malnutrition. AB - Wegener's granulomatosis (WG) is a systemic disease with a complex genetic background. It is characterised by inflammation of the small blood vessels leading to damage in any number of organs. The common features include granulomatous inflammation of the respiratory tract and kidneys. Most patients have measurable autoantibodies against neutrophil proteinase-3 (Antineutrophil Cytoplasmic Antibody, ANCA). Pituitary involvement is a rare complication of this disease and, when it occurs, diabetes insipidus is the most common manifestation. We describe a 38-year-old female with known long-term WG who presented with partial hypopituitarism, severe malnutrition and ANCA negative status, with a favourable response to steroid pulse therapy. PMID- 22673711 TI - Hydatid cyst in tail of pancreas. AB - The authors present a case of hydatid cyst in tail of pancreas in a 35-year-male who presented with 6-month history of dull aching pain in abdomen. Radiologically, a differential diagnosis of cystic pancreatic neoplasm and pseudocyst was made which was confirmed after histopathological examination. PMID- 22673712 TI - Extranodal marginal zone B cell lymphoma of MALT type with extensive plasma cell differentiation in a man with Hashimoto's thyroiditis. AB - Primary thyroid gland lymphomas are uncommon tumours that occur in the setting of lymphocytic thyroiditis or Hashimoto's disease in almost all cases. Rarely these tumours show extensive plasmacytic differentiation. In these conditions, a distinction between an inflammatory thyroid infiltrate and extramedullary plasmacytoma may be extremely difficult and precise criteria and ancillary techniques are necessary for a correct diagnosis. The authors report a case of mucosa associated lymphoid tissue (MALT) lymphoma of the thyroid gland in a 69 year-old Iranian man with Hashimoto's thyroiditis which was diagnosed by means of immunohistochemical stains. This case demonstrates that histology may not distinguish between extramedullary plasmacytoma and MALT lymphoma of the thyroid gland and the use of immunohistochemical staining stains were essential to prove definite diagnosis. PMID- 22673713 TI - An unusual case of pneumocephalus. AB - The authors present an unusual cause of pneumocephalus in a previously fit and well female octogenarian who presented with acute onset altered level of consciousness and generalised weakness. Radiological imaging demonstrated widespread cerebritis with pneumocephalus and gas within the superior sagittal sinus. Blood culture grew Clostridium septicum, a virulent but rare organism that can infect normal tissues. The close association between C septicum and both haematological and bowel malignancies must be considered if this organism is cultured. PMID- 22673714 TI - Bowel obstruction caused by intestinal tuberculosis: an update. AB - Tuberculosis is one of the most important communicable diseases worldwide, with an increasing incidence within the UK. The abdomen is involved in 11% of patients with extra-pulmonary tuberculosis, and can provide a diagnostic challenge if not suspected. The authors report the case of a 31-year-old Sudanese female who presented with intestinal obstruction due to a mass caused by abdominal tuberculosis. Imaging revealed evidence of multifocal tuberculosis involving the ileo-caecal region with abdominal and mediastinal lymphadenopathy. She went on to have a limited right hemicolectomy and completed antitubercular therapy. It is important to consider abdominal tuberculosis when conditions such as Crohn's disease or gastrointestinal malignancy are being entertained in those from a high risk background. Since diagnosis can be difficult, if clinical suspicion is strong, surgery is a safe option. Recommended management combines up to 12 months of antitubercular therapy with conservative surgery. PMID- 22673715 TI - Happy ending of life-threatening upper GI bleeding. AB - Strongyloides stercoralis is an intestinal nematode in humans, and estimated about tens of millions of people are infected worldwide. This parasite is endemic in tropical or temperate and subtropical climates like Bangladesh. The authors report a 33-year-old man who presented with recurrent life-threatening upper gastrointestinal bleeding from gastric infection by S stercoralis. PMID- 22673716 TI - Closure of a persistent cyclodialysis cleft using the haptics of a normal-sized intraocular lens. AB - A 50-year-old man suffering from hypotony in the right eye caused by a traumatic cyclodialysis and complicated by a choroidal detachment and cataract was treated in our clinic. After an unsuccessful direct cyclopexy, phacoemulsification was performed and a normal-sized single-piece polymethyl methacrylate posterior chamber intraocular lens (PMMA PCIOL) was inserted into the ciliary sulcus, with the haptic rotated toward the cyclodialysis cleft. Postoperatively, the corrected visual acuity improved to 20/20, and the intraocular pressure returned to normal. Ultrasound biomicroscopy showed the closure of the cleft. Phacoemulsification with a normal-sized PMMA PCIOL inserted into the ciliary sulcus is a safe, effective and technically simple surgical treatment for small cyclodialysis induced hypotony complicated by cataract. Internal compression of the cleft by the haptic of a normal sized IOL along with postoperative inflammation led to scarring and closure of the cleft. PMID- 22673717 TI - Synovial osteochondromatosis associated with osteoarthrits causing ulnar nerve palsy. AB - Synovial oteochondromatosis has been described in the knee joint commonly but this case was in the elbow and was associated with ulnar nerve palsy. Generally it has been the belief that synovial osteochondromatosis is not associated with ostearthritis of the joint but, in this case it was clearly associated with osteoarthritis of the elbow. Therefore the authors wish to report this case of a rare condition with an unusual association. PMID- 22673718 TI - Effect of skin fibroblast-derived allogeneic feeder cells on porcine ES-like cell establishment. AB - In the present study, the effect of two types of allogeneic-derived feeder cells [porcine ear and tail skin fibroblasts (PESF, PTSF)] and three types of xenogeneic-derived feeder cells [human foreskin fibroblasts (HFK), mouse embryonic fibroblasts (MEF) and immortalized mouse embryonic fibroblasts (STO)] on the isolation and cultivation of putative porcine embryonic stem cells (pESCs) was evaluated. In vivo derived zona pellucida (ZP)-free blastocysts were cultured on different mitotically inactivated feeder layers. The rates of ICM outgrowth and primary colony formation were observed, and further passage onto new feeders was performed. The characteristics of pESCs, including alkaline phosphatase (AP) activity, and pluripotent-related markers (OCT3/4, NANOG, SSEA-4) and genes were examined. Attached blastocysts cultured on HFK and STO feeders showed a higher percentage of ICM outgrowths than those cultured on PESF (76.7, 72.9 and 38.9%, respectively; P<0.05). The rates of primary ES-like colony formation and the number of putative ESC lines were significantly decreased when ICM outgrowths were cultured on PESF, compared with those cultured on HFK (30.6 vs. 76.7%, respectively; P<0.05). Only ES-like colonies from one (25%) and three (50%) cell lines developed on PTSF and STO feeders, respectively, were further maintained in an undifferentiated morphology associated with the presence of all ES characteristics; however, these characteristics disappeared when colonies were continued to the 8th and 6th passages, respectively. The present study indicated that feeder cell types affect the success of pESC establishment and maintenance of their pluripotency. PMID- 22673719 TI - A histologic study on growth promoter target organs of slaughtered beef in Molise Region (Italy). AB - A gross pathology and histological investigation was carried out on bovine target organs of anabolic substances in the Molise Region (Italy). One hundred forty four bovines (12-24 months old, 123 males and 21 females) were included in the survey. An antemortem assessment of their behavior and clinical examination were performed. After slaughter, samples of prostate, Cowper's glands, Bartholin's glands, mammary gland, ovaries, thymus and thyroid were collected, inspected and processed for histopathology, as suggested in the guidelines of the Italian national program for residue surveillance (PNR). Overall, 15.3% of the examined animals were classified as "suspect," 44.4% were classified as "uncertain," and the remaining 40.3% were classified as "negative." The most frequent lesion was a severe thymus atrophy with fat infiltration (15.4% of males and 14.3% of females), strongly suggesting the illegal use of corticosteroids. PMID- 22673721 TI - Antimicrobial resistance of Salmonella serovars isolated from beef at retail markets in the north Vietnam. AB - Approximately 39.9% (63/158) of beef samples collected from retail markets in Hanoi from January to June 2009 were Salmonella-positive. Nine Salmonella serovars, Anatum (28.6%), Rissen (25.4%), Weltevreden (12.7%), Typhimurium (7.9%), Derby (7.9%), Lexington (7.9%), Dublin (4.6%), Newport (3.2%) and London (1.8%), were identified. Thirty-seven (58.7%) of the 63 Salmonella isolates were resistant to at least one antimicrobial tested, of which 29 (46%) isolates showed multidrug resistance (MDR). The isolates were commonly resistant to tetracycline (46.0%), sulphonamide (39.7%), ampicilline (31.7%), streptomycin (30.2%), trimethoprim (28.6%), kanamycin (28.6%) and chloramphenicol (22.2%). Fourteen (bla(TEMV), bla(OXA-1), aadA1, aadA2, sul1, tetA, tetB, tetG, cmlA1, floR, dfrA1, dfrA12, aac (3)-IV and aphA1-1AB) out of 22 antimicrobial resistance genes were detected by PCR from the resistant isolates. The catA1, Kn, blaPSE-1 genes and plasmid-mediated quinolones resistance (PMQR) genes such as qnrA, qnrB, qnrS, qepA and acc (6')-ib-cr were not detected. Mutations in the gyrA gene leading to the amino acid changes Ser83Phe and/or Asp87Asn were found in 6 out of the 11 quinolone-resistant isolates. The data revealed that multidrug resistant Salmonella strains were widely distributed in north Vietnam via the food chain and might contain multiple genes specifying identical resistant phenotypes. Thus, continuous studies are necessary to clarify the mechanisms of MDR in Salmonella and its spread in the livestock market. PMID- 22673720 TI - Studies on hantavirus infection in small mammals captured in southern and central highland area of Vietnam. AB - To investigate the distribution of hantaviruses among animals in Southern and Central Highland area of Vietnam, a total of 1311 serum samples were obtained from rats and Asian house shrews (Suncus murinus) captured at 11 locations between 2006 and 2009. A total of 1066 serum samples from rats were examined for IgG antibodies against Hantaan virus, and there were 30 antibody-positive serum samples from rats that had been captured mainly in a port area and urban area in Ho Chi Minh City (HCMC) (2.8%). All of the antibody-positive rats were Rattus norvegicus, and they had Seoul virus (SEOV) genome in their lungs. SEOV sequences detected from rats captured in Southern Vietnam belonged to the same lineage as those from rats captured at Haiphong Port and a market area in Hanoi City. SEOV strain CSG5 was isolated from a rat captured at Saigon Harbor. Strain CSG5 showed a cross-neutralization pattern almost the same as that of a representative strain of SEOV. A total of 245 Asian house shrews were captured in the Central Highland area and near HCMC. Sera were examined for IgG antibodies against Thottapalayam virus (TPMV), and 32 (13.1%) of the antibody-positive shrews were mainly from the Central Highland area and showed a neutralizing antibody against TPMV. These results indicated that SEOV is distributed among R. norvegicus inhabiting harbor and urban areas of Southern Vietnam and that TPMV or an antigenically related virus is distributed among Asian house shrews in Central Highland area. PMID- 22673722 TI - Estrus cycle-related preference of BALB/c female mice for C57BL/6 males is induced by estrogen. AB - The odor preference of female mice for male odor is reported to have cyclical variations in relation to the estrus cycle. Females prefer the odor of genetically dissimilar males to that of genetically similar ones, but the causal relation between this preference and the estrus cycle has scarcely been investigated. The Y-maze test demonstrated that BALB/c females stayed for a longer duration near the urine of C57BL/6 males than that of BALB/c males when they were in metestrus, diestrus and proestrus, but not in estrus. The prolonged stay disappeared after ovariectomy, and administration of estradiol-17beta restored the tendency. The present results suggest that the odor preference of BALB/c females for C57BL/6 over BALB/c males temporally changes according to the estrus cycle and that estrogen can be one of endogenous factors regulating this phenomenon. PMID- 22673723 TI - Prevalence of swine hemoplasmas revealed by real-time PCR using 16S rRNA gene primers. AB - Hemoplasma is a tribal name for epierythrocytic mycoplasmas including Mycoplasma suis and M. parvum which are currently recognized in pigs as causative of porcine hemoplasmosis. Here, we report a real-time PCR assay for differential detection of these swine hemoplasma species by using allelic primers in the16S rRNA gene, and its application to survey for hemoplasma infections in pigs. Universal primers and species-specific primers were designed and evaluated by using swine blood samples positive in hemoplasmas. Mycoplasma suis and M. parvum infections were both confirmed by universal primers, and mixed infections were clearly distinguished by species-specific primers. Further, we applied this real-time PCR assay to 120 swine blood specimens from clinically healthy pigs in eleven farms in Japan, and found six (5.0%) were positive for M. suis and 18 (15.0%) were positive for M. parvum, and three (2.5%) were mixed infection by both hemoplasma species. PMID- 22673724 TI - FDG uptake of normal canine brain assessed by high-resolution research tomography positron emission tomography and 7 T-magnetic resonance imaging. AB - The purpose of this study was to assess the normal distribution of (18)F-fluoro-2 deoxy-D-glucose (FDG) uptake of canine brain structures using a high-resolution research tomography-positron emission tomography (HRRT-PET) and 7 T-magnetic resonance imaging (MRI) fusion system. FDG-PET and T2-weighted MRI of the brain were performed on 4 healthy laboratory beagle dogs. On MRI, regions of interests (ROIs) were manually drawn over 51 intracranial structures, including nine gross structures and 42 detailed structures. Relative standard uptake value ratio (rSUV=SUV of ROI/SUV of whole brain) was calculated for each ROI. The HRRT-PET and 7 T-MRI fusion imaging system demonstrated significant differences in glucose metabolism among various intracranial structures. Among gross structures, the midbrain and the pons and medulla oblongata had the highest uptake (rSUV: 1.12 +/ 0.03) and lowest uptake (rSUV: 0.90 +/- 0.06) of FDG, respectively. When rSUVs were calculated on detailed regions, the caudal colliculus and the longitudinal fibers of pons had the highest (rSUV: 1.62 +/- 0.05) and the lowest (rSUV: 0.63 +/- 0.03) glucose metabolism, respectively. Because the high resolution of PET MRI fusion images provided clearly identifiable metabolic activities of canine brain, the HRRT-PET and 7 T-MRI fusion imaging might be a good tool for evaluation of intracranial diseases in canines. PMID- 22673725 TI - Prevalence and risk factor analysis of bovine hemoplasma infection by direct PCR in Eastern Hokkaido, Japan. AB - The prevalence and risk factors of 2 bovine hemoplasma species-Mycoplasma wenyonii (Mw) and "Candidatus Mycoplasma haemobos" (CMh)-were examined by direct PCR using whole blood samples collected from 343 cattle in Eastern Hokkaido, Japan. The sensitivity of the direct PCR assay was 10-fold higher than the standard PCR assay, detecting 5 copies of bovine hemoplasma DNA per reaction. An epidemiological survey of sampling location, living conditions, age and bovine leukemia virus antibody was performed to assess infection risk factors. The prevalence rates were 38.5% for Mw and 39.1% for CMh, respectively, with an overall prevalence rate of 64.7% for all bovine hemoplasma infections. Significant differences were found in sampling location, living conditions and age. Compared with pastured cattle, farmed cattle were significantly more susceptible to infection with total hemoplasma species (P<0.001), and were particularly susceptible to CMh (P<0.001). Cattle that were 1-3 years of age were more susceptible to infection with hemoplasma compared with other age groups. Bovine leukemia virus infection status was not significantly associated with hemoplasma infections. Blood examination revealed significantly lower RBC, Hb, and PCV levels, and a higher MCV in infected cattle than in noninfected cattle. PMID- 22673726 TI - Use of fractional dose-volume histograms to model risk of acute rectal toxicity among patients treated on RTOG 94-06. AB - BACKGROUND AND PURPOSE: For toxicities occurring during the course of radiotherapy, it is conceptually inaccurate to perform normal-tissue complication probability analyses using the complete dose-volume histogram. The goal of this study was to analyze acute rectal toxicity using a novel approach in which the fit of the Lyman-Kutcher-Burman (LKB) model is based on the fractional rectal dose-volume histogram (DVH). MATERIALS AND METHODS: Grade >=2 acute rectal toxicity was analyzed in 509 patients treated on Radiation Therapy Oncology Group (RTOG) protocol 94-06. These patients had no field reductions or treatment-plan revisions during therapy, allowing the fractional rectal DVH to be estimated from the complete rectal DVH based on the total number of dose fractions delivered. RESULTS: The majority of patients experiencing Grade >=2 acute rectal toxicity did so before completion of radiotherapy (70/80=88%). Acute rectal toxicity depends on fractional mean rectal dose, with no significant improvement in the LKB model fit when the volume parameter differs from n=1. The incidence of toxicity was significantly lower for patients who received hormone therapy (P=0.024). CONCLUSIONS: Variations in fractional mean dose explain the differences in incidence of acute rectal toxicity, with no detectable effect seen here for differences in numbers of dose fractions delivered. PMID- 22673727 TI - FET-PET assessed recurrence pattern after radio-chemotherapy in newly diagnosed patients with glioblastoma is influenced by MGMT methylation status. AB - BACKGROUND AND PURPOSE: The aim of the present study was to evaluate factors predicting the recurrence pattern determined by [(18)F]FET-PET imaging in patients with newly diagnosed glioblastoma after combined radio-chemotherapy treated according to the EORTC/NCIC trial. MATERIAL AND METHODS: Seventy-nine patients with newly diagnosed GBM treated with radiotherapy plus temozolomide (75 mg/m(2)/d) followed by adjuvant cyclic (5/28 days) temozolomide (150-200 mg/m(2)) were retrospectively analysed. Recurrence patterns were assessed by means of positron-emission-tomography with [(18)F]FET and additional MRI; in 54 patients MGMT methylation status was evaluated. RESULTS: Whilst 49.4% of the patients had an in-field recurrence, 12.6% an ex-field recurrence and 3.8% a recurrence at the field margin, 34.2% of the patients did not relapse during follow-up (median 595 days). Considering all patients included in this study, 41.5% (12/29) of the MGMT methylated population had no relapse, 37.9% (11/29) had an in-field-recurrence and 20.7% (6/29) an ex-field/marginal recurrence, whilst 28.0% (7/25) of the MGMT unmethylated population had no relapse, 64.0% (16/25) had an in-field-recurrence and 8.0% (2/25) an ex-field/marginal recurrence (p=0.15). CONCLUSIONS: After the administration of temozolomide concomitant with and adjuvant to radiotherapy in patients with glioblastoma, the pattern determined by [(18)F]FET-PET seems to be associated with MGMT methylation status. PMID- 22673728 TI - Large prostate motion produced by anal contraction. AB - BACKGROUND AND PURPOSE: The aim of this study was to define the effects of voluntary anal contraction on prostate motion in an experimental setting. MATERIALS AND METHODS: Thirty-eight patients (median age, 76 years) with prostate cancer underwent thin-slice computed tomography (CT) in the vicinity of the prostate before and after active anal contraction. Three-dimensional displacement of the pelvis and prostate was measured. RESULTS: Mean (+/-standard deviation, SD) overall displacement of the prostate due to anal contraction was 0.3+/-1.4 mm to the right, 9.3+/-7.8 mm to the anterior, and 5+/-4 mm to the cranial direction. Mean displacement of the pelvis was 0.5+/-1.8 mm to the right, 4.1+/ 7.1 mm to the anterior, and 1+/-3 mm to the cranial direction. Mean displacement of the prostate relative to the pelvis was 0.1+/-1.1 mm to the left, 5.2+/-3.3 mm to the anterior, and 4+/-4 mm to the cranial direction. CONCLUSIONS: Voluntary anal contraction within an experimental setting induces large prostate and bone motion, mainly in the anterior and cranial directions. The frequency and magnitude of actual anal contractions during radiotherapy for prostate cancer need to be determined. PMID- 22673729 TI - Role of Tip60 in human melanoma cell migration, metastasis, and patient survival. AB - The tumor suppressor Tip60 regulates gene transcription, DNA damage response, apoptosis, and cancer development, but its role in melanoma is unknown. In this study, we investigated the expression pattern of Tip60 in melanoma and assessed its prognostic value. Using tissue microarrays consisting of 448 cases of melanomas (201 for the training set and 247 for the validation set) and 105 cases of nevi, we found that Tip60 expression was significantly reduced in metastatic melanoma compared to common nevi (P=0.045), dysplastic nevi (P=0.047), and primary melanoma (P=0.001). Kaplan-Meier survival curve and univariate Cox regression analyses showed that reduced Tip60 expression was associated with a poorer 5-year disease-specific survival in primary melanoma (P=0.016) and metastatic melanoma patients (P=0.027). Multivariate Cox regression analyses indicated that Tip60 expression was an independent prognostic marker for primary (P=0.024) and metastatic melanomas (P=0.035). In vitro wound healing assay showed that enforced Tip60 expression inhibited but Tip60 knockdown enhanced melanoma cell migration, suggesting that Tip60 might regulate melanoma metastasis. Finally, we showed that overexpression of Tip60 in melanoma cells resulted in significantly increased chemosensitivity. Our data indicate that Tip60 may serve as a potential biomarker for melanoma patient outcome as well as a potential therapeutic target. PMID- 22673730 TI - NF-kappaB accumulation associated with COL1A1 transactivators defects during chronological aging represses type I collagen expression through a -112/-61-bp region of the COL1A1 promoter in human skin fibroblasts. AB - The aging process, especially of the skin, is governed by changes in the epidermal, dermo-epidermal, and dermal compartments. Type I collagen, which is the major component of dermis extracellular matrix (ECM), constitutes a prime target for intrinsic and extrinsic aging-related alterations. In addition, under the aging process, pro-inflammatory signals are involved and collagens are fragmented owing to enhanced matrix metalloproteinase activities, and fibroblasts are no longer able to properly synthesize collagen fibrils. Here, we demonstrated that low levels of type I collagen detected in aged skin fibroblasts are attributable to an inhibition of COL1A1 transcription. Indeed, on one hand, we observed decreased binding activities of specific proteins 1 and 3, CCAAT-binding factor, and human collagen-Kruppel box, which are well-known COL1A1 transactivators acting through the -112/-61-bp promoter sequence. On the other hand, the aging process was accompanied by elevated amounts and binding activities of NF-kappaB (p65 and p50 subunits), together with an increased number of senescent cells. The forced expression of NF-kappaB performed in young fibroblasts was able to establish an old-like phenotype by repressing COL1A1 expression through the short -112/-61-bp COL1A1 promoter and by elevating the senescent cell distribution. The concomitant decrease of transactivator functions and increase of transinhibitor activity is responsible for ECM dysfunction, leading to aging/senescence in dermal fibroblasts. PMID- 22673732 TI - Regulation of IL-33 expression by IFN-gamma and tumor necrosis factor-alpha in normal human epidermal keratinocytes. AB - IL-33, a member of the IL-1 family, is implicated in type 2 T helper cell immune reactions and acts as an "alarmin" to induce activation of dendritic cells in response to external stimuli. We investigated the effect of inflammatory cytokines on IL-33 expression in normal human epidermal keratinocytes. IFN-gamma dose- and time-dependently induced IL-33 expression in protein and mRNA; this was dependent on extracellular signal-regulated kinase, p38, EGFR, and JAK phosphorylation. Combined IFN-gamma and tumor necrosis factor (TNF)-alpha treatment induced expression of a 20-kDa band corresponding to mature IL-33, which was abolished by the addition of a calpain inhibitor. The addition of the inhibitor to IFN-gamma and TNF-alpha-stimulated cells also induced strong expression of a 25-kDa band. Small interference (si) RNA for IL-33 abolished expression of the smaller bands and the 30-kDa IL-33 band, suggesting that these IL-33 forms were IL-33 transcription products. Recombinant IL-33 added in the medium induced IL-8 production, and RNA knockdown by siRNA enhanced IL-8 expression, suggesting its dual role as a cytokine and a nuclear factor. These results indicate that IL-33 has a role in inflammatory skin diseases, in which IFN-gamma and TNF-alpha are present in high levels. PMID- 22673734 TI - Defect-less, layered organo-titanosilicate with superhydrophobicity and its catalytic activity in room-temperature olefin epoxidation. AB - A new type of defect-less, layered organo-titanosilicate is synthesized using a simple, template-free, evaporation-induced self-assembly process. The obtained layered material has superhydrophobicity and exhibits promising catalytic activity in the epoxidation of olefins using 30% H(2)O(2) aqueous solution as oxidant at room temperature. PMID- 22673731 TI - The emerging role of IL-17 in the pathogenesis of psoriasis: preclinical and clinical findings. AB - Although the histological changes seen in psoriasis have long been well characterized, the underlying cellular and molecular mechanisms have only begun to be elucidated over the past 20 years. Proinflammatory factors such as tumor necrosis factor (TNF)-alpha have a central role in psoriasis pathogenesis, and many T-helper 1 (Th1) cytokines and messenger RNAs are elevated in psoriatic lesions. IL-17A, IL-17F, and other Th17 cell-derived cytokines have been shown in murine models to induce features that mimic human psoriasis. This review focuses on the emerging biology of the IL-17 cytokine family in psoriasis, and on the molecular and genetic information gained from animal models and human clinical studies that confirm IL-17 as a crucial proinflammatory cytokine in psoriasis. Expression of IL-17A, IL-17C, and IL-17F is strikingly increased in psoriatic lesions, and successful therapy is associated with restoration of the expression of a wide range of genes (including effector molecules downstream of IL-17 such as cytokines, chemokines, and antimicrobial peptides) to near-normal levels. Therapeutic agents in development that target IL-17 are discussed, and an emerging model of the key role of IL-17 in the pathogenesis of psoriasis is presented. PMID- 22673733 TI - Mechanism of a flow-gated angiogenesis switch: early signaling events at cell matrix and cell-cell junctions. AB - A bias towards angiogenesis from the venous circulation has long been known, but its cause remains unclear. Here we explore the possibility that high interstitial pressure in tumors and the resultant net filtration pressure gradient that would induce flow from the interstitium into the venous circulation or lymphatics could also be an important mechanical regulator of angiogenesis. The objective of this study was to test the hypothesis that basal-to-apical (B-A) transendothelial flow promotes angiogenesis and to investigate potential mechanisms. Macro- and microvascular endothelial monolayers were cultured on type I collagen gels in a microfluidic cell culture device and subjected to apical-to-basal (A-B) and B-A transendothelial flows. Samples were perfusion fixed and analyzed for morphological responses, localization and degree of phosphorylation of certain signaling proteins. Application of B-A, but not A-B flow, to cultured endothelial monolayers was found to promote capillary morphogenesis and resulted in distinct localization patterns of VE-cadherin and increased FAK phosphorylation. These results suggest that B-A flow triggers the transition of vascular endothelial cells from a quiescent to invasive phenotype and that the flow-mediated response involves signaling at cell-cell and cell-matrix interfaces. These results support the hypothesis that transendothelial pressure gradients resulting in B-A flow promotes sprouting angiogenesis and are consistent with early observations that tumor angiogenesis occurs from the venous side of the circulation. PMID- 22673735 TI - [Community-acquired Staphylococcus aureus necrotizing pneumonia secreting Panton Valentine leukocidin in an infant]. AB - Staphylococcus aureus (SA) necrotizing pneumonia secreting Panton-Valentine leukocidin (PVL) has a high mortality rate, approximately 50% according to recent data, mainly in children and young adults. Recently, 2 cases of the disease have been reported in newborn twins with a good outcome. We report a third case of community-acquired necrotizing pneumonia due to SA sensitive to methicillin (SASM) secreting Panton-Valentine leukocidin (PVL) in an infant, initially paucisymptomatic, in the context of familial furunculosis, with a fatal outcome. Cases of necrotizing pneumonia in this age group are emerging, and extensive information for clinicians is needed due to the high mortality rate of the disease. PMID- 22673736 TI - [Subdural empyema complicating meningococcal meningitis: a pediatric observation]. AB - Postmeningitis subdural empyema is rare in infants. It can have a severe clinical course with possible serious long-term consequences and 10% mortality. Diagnosis is often difficult. Postmeningitis subdural empyema must be discussed in cases of atypical progression of well-treated meningitis. We report the case of an 18 month-old infant presenting subdural empyema with an insidious course following Neisseria meningitidis group C meningitis. PMID- 22673737 TI - Effect of all-trans retinoic acid on the growth of two nasopharyngeal cancer cell lines and its treatment potential in combination with cisplatin. AB - The purpose of this study was to determine the effect of all-trans retinoid acid (ATRA) on two nasopharyngeal cancer (NPC) cell lines and to evaluate the synergistic effect of ATRA used in combination with cisplatin, a standard chemotherapeutic agent for NPC. Two NPC cell lines (NPC-TW01 and NPC-TW04) were used, and the MTT assay was used to analyze cell growth inhibition under various concentrations of ATRA and cisplatin. Under low concentrations of ATRA, the growth of both cell lines was significantly inhibited. When ATRA was used in combination with cisplatin, the resulting synergistic effects were robust and significant. Only a low concentration of ATRA was required to produce a synergistic effect when combined with cisplatin, indicating the potential usefulness of a combination therapy regimen. Therefore, the combination of ATRA and cisplatin is a viable treatment option for NPC and should be further investigated. PMID- 22673738 TI - Low dose macrolide administration for long term is effective for otitis media with effusion in children. AB - OBJECTIVE: To explore the clinical effect and possible mechanism of macrolides on otitis media with effusion in children. METHODS: Children with otitis media with effusion were recruited and prescribed for macrolides according to a designed scheme, and followed up for 8-12 weeks. Middle ear effusion samples were collected from the participants to assess the presence of biofilm. RESULTS: Macrolides were found to have significant effect on the therapy of early stage otitis media with effusion for 88.7-92.5% of participants compared with 50.9 60.3% in control group after 8-12 weeks. Almost 72.1% of chronic otitis media with effusion patients recovered after an 8 weeks' course low dose macrolides prescription. Biofilm occurred in 30.8% (4/13) of middle ear effusion. CONCLUSIONS: The results indicate that macrolides are effective for otitis media with effusion in children. Bacterial biofilm may play an important role in the pathogenesis of otitis media with effusion. PMID- 22673739 TI - Dermatological manifestations of palifermin therapy: a common side effect of its use in oncology. PMID- 22673740 TI - Sorafenib and pemetrexed toxicity in cancer cells is mediated via SRC-ERK signaling. AB - The present studies sought to further understand how the anti-folate pemetrexed and the multi-kinase inhibitor sorafenib interact to kill tumor cells. Sorafenib activated SRC, and via SRC the drug combination activated ERK1/2. Expression of dominant negative SRC or dominant negative MEK1 abolished drug-induced ERK1/2 activation, together with drug-induced autophagy, acidic lysosome formation, and tumor cell killing. Protein phosphatase 2A is an important regulator of the ERK1/2 pathway. Fulvestrant resistant MCF7 cells expressed higher levels of the PP2A inhibitor SET/I2PP2A, had lower endogenous PP2A activity, and had elevated basal ERK1/2 activity compared with their estrogen dependent counterparts. Overexpression of I2PP2A blocked drug-induced activation of ERK1/2 and tumor cell killing. PP2A can be directly activated by ceramide and SET/I2PP2A can be inhibited by ceramide. Inhibition of the de novo ceramide synthase pathway blocked drug-induced ceramide generation, PP2A activation and tumor cell killing. Collectively these findings demonstrate that ERK1/2 plays an essential role downstream of SRC in pemetrexed and sorafenib lethality and that PP2A plays an important role in regulating this process. PMID- 22673742 TI - Structural and thermodynamic characterization of the self-adhesive properties of human P-cadherin. AB - Human P-cadherin is a promising therapeutic target against cancer. However, its characterization at the molecular level is still lacking. We report that human P cadherin associated irreversibly in a distinct dimer configuration. Unexpectedly, the divalent cation Ca2+ was not necessary for dimerization, although it greatly stabilized the protein-protein complex. PMID- 22673741 TI - [A reversible cause of dilated cardiomyopathy: hypocalcemia]. AB - BACKGROUND: Hypocalcemia is very rare reversible cause of dilated cardiomyopathy (DCMP) witch can concern one or both ventricules. We here presented two cases of DCMP that caused by hypocalcemia and recovered totally after oral calcium and vitamin D supplementation. CASE PRESENTATION 1: A 29-year-old Caucasian female was admitted in our hospital due to congestive heart failure with dyspnea (NYHA class IV) and generalized edema for 2days. She had a history of total thyroidectomy one year a go. She had taken synthyroid as a daily medication associated to calcium supplementation and vitamin D because of hypoparathyroidism. Patient was not compliant to treatment. Trans thoracic echocardiography (TTE) showed a dilated left ventricule (LV) with global hypokinesia with 28% of left ventricule ejection and moderate mitral regurgitation. Laboratory test showed a severe hypocalcemia. After correction of hypocalcemia, there was a clear clinical improvement and four months later a total recovery was found. CASE PRESENTATION 2: A 44-year-old Caucasian male was referred to the hospital for rebel congestive heart failure with dyspnea and edema of lower limbs despite optimal treatment. Patient had no medical past history. TEE showed dilated cardiomyopathy with severe alteration of left ventricule systolic function (25%). Biological tests showed a hypocalcemia and primary hypoparathyroidism. An improvement of symptoms after correction of metabolic disorder was found. LV gradually recovered its performance. CONCLUSION: Patients outcome in end stage heart failure is different from the classical outcomes in patients with hypocalcemia induced heart disease. DCMP induced by hypocalcemia should be considered in patients with heart failure associated with medical conditions leading to hypocalcemia. It requires a specific treatment. PMID- 22673743 TI - Endothelial dysfunction in rheumatic autoimmune diseases. AB - Rheumatic autoimmune diseases have been associated with accelerated atherosclerosis and various types of vasculopathies. Atherosclerosis is an inflammatory condition which starts as a "response to injury" favoring endothelial dysfunction which is associated with increased expression of adhesion molecules, pro-inflammatory cytokines, pro-thrombotic factors, oxidative stress upregulation and abnormal vascular tone modulation. Endothelial dysfunction in rheumatic autoimmune diseases involves innate immune responses, including macrophages and dendritic cells expression of scavenger and toll-like receptors for modified or native LDL as well as neutrophil and complement activation, and dysregulation of adaptive immune responses, including proliferation of autoreactive T-helper-1 lymphocytes and defective function of dendritic and regulatory T cells. Specific differences for endothelial function among different disorders include: a) increased amounts of pro-atherogenic hormones, decreased amounts of anti-atherogenic hormones and increased insulin resistance in rheumatoid arthritis; b) autoantibodies production in systemic lupus erythematosus and antiphospholipid syndrome; c) smooth muscle cells proliferation, destruction of internal elastic lamina, fibrosis and coagulation and fibrinolytic system dysfunction in systemic sclerosis. Several self-antigens (i.e. high density lipoproteins, heat shock proteins, beta2-glycoprotein1) and self-molecules modified by oxidative events (i.e. low density lipoproteins and oxidized hemoglobin) have been identified as targets of autoimmune responses. Endothelial dysfunction leads to accelerated atherosclerosis in rheumatoid arthritis, systemic lupus erythematosus and spondyloarthropaties whereas obliterative vasculopathy is associated with systemic sclerosis. In this paper, we will briefly review the most relevant information upon endothelial dysfunction and inflammatory mechanisms in atherosclerosis and we will summarize the similarities and differences in vascular disease patterns underlying different rheumatic autoimmune diseases. PMID- 22673744 TI - Intensity-modulated radiotherapy in the treatment of prostate cancer. AB - Three-dimensional conformal radiotherapy (3DCRT) as the primary treatment for prostate cancer has improved outcomes compared with conventional radiotherapy, but with an associated increase in toxicity due to radiation effects on the bladder and rectum. Intensity-modulated radiotherapy (IMRT) is a newer method of radiotherapy that uses intensity-modulated beams that can provide multiple intensity levels for any single beam direction and any single source position allowing concave dose distributions and dose gradients with narrower margins than those possible using conventional methods. IMRT is ideal for treating complex treatment volumes and avoiding close proximity organs at risk that may be dose limiting and provides increased tumour control through an escalated dose and reduces normal tissue complications through organ at risk sparing. Given the potential advantages of IMRT and the availability of IMRT-enabled treatment planning systems and linear accelerators, IMRT has been introduced in a number of disease sites, including prostate cancer. This systematic review examined the evidence for IMRT in the treatment of prostate cancer in order to quantify the potential benefits of this new technology and to make recommendations for radiation treatment programmes considering adopting this technique. The findings were in favour of recommending IMRT over 3DCRT in the radical treatment of localised prostate cancer where doses greater than 70 Gy are required, based on a review of 11 published reports including 4559 patients. There were insufficient data to recommend IMRT over 3DCRT in the postoperative setting. Future research should examine image-guided IMRT in the post-prostatectomy setting, with altered fractionation, and in combination with hormone and chemotherapy. PMID- 22673746 TI - Recent advances on NOTCH signaling in T-ALL. AB - NOTCH1 receptor signaling plays a central role in T-cell lineage specification and in supporting the growth and proliferation of immature T-cell progenitors in the thymus during lymphoid development. In T-cell acute lymphoblastic leukemia (T ALL), a tumor resulting from the malignant transformation of T-cell progenitors, aberrant and constitutively active NOTCH1 signaling triggered by activating mutations in the NOTCH1 gene contributes to oncogenic transformation and is a hallmark of this disease. Most notably, small molecule gamma-secretase inhibitors (GSIs) can effectively block NOTCH1 signaling in T-ALL, and could be exploited as a targeted therapy in this disease. In addition, a number of emerging anti-NOTCH therapeutic strategies including anti-NOTCH1 inhibitory antibodies, small peptide inhibitors of NOTCH signaling and combination therapies with GSIs and glucocorticoids, have recently been proposed. Finally, the identification of NOTCH1 mutations in solid tumors and chronic lymphocytic leukemias has increased even further the clinical relevance of NOTCH signaling as a therapeutic target in human cancer. Here we review our current understanding of NOTCH1-induced transformation, the mechanisms of action of oncogenic NOTCH1 in T-ALL and the therapeutic and prognostic implications of NOTCH1 mutations in T-ALL. PMID- 22673745 TI - Divergence of Rho residue 43 impacts GEF activity. AB - RhoA, RhoB and RhoC GTPases are over 85% identical at the amino acid level, with RhoA and RhoC differing at only one residue (43) across the initial two-thirds of their sequences. A putative regulatory distinction between the molecules is their capacity to be uniquely activated by guanine nucleotide exchange factors (GEFs). We hypothesize that variation of amino acid residue 43 between RhoA/B (valine) and RhoC (isoleucine) impacts GEF activity. Direct participation of residue 43 in GEF-catalyzed exchange was confirmed by the observation that mutation of this position to a threonine reduced GEF-catalyzed nucleotide exchange activity in vitro (Vav2, XPLN, GEFT, Dbl and Dbs) and greatly depressed RhoA and RhoC GTP loading profiles in cell lysates. Using a residue swap approach, substitution of RhoA Val 43 with an Ile was found to significantly promote basal nucleotide exchange activity and enhance GTP-loading in cells. Substitution of Val 43 with an Ile in RhoB negatively affected nucleotide exchange in vitro. Substitution of RhoC Ile 43 with a Val increased GEF-catalyzed exchange in vitro. In addition, RhoC-I43V was more efficacious at driving ovarian cancer cell invasion through matrigrel than wild-type RhoC, RhoC-I43T, wild-type RhoA, RhoA-V43I or RhoA-V43T GTPases. These findings suggest that a divergence between RhoA/B and RhoC at residue 43 impacts basal and GEF-stimulated nucleotide exchange activity. PMID- 22673747 TI - Hematology and serum biochemistry values in five captive finless porpoises (Neophocaena phocaenoides). AB - Hematological and serum biochemical values in five captive finless porpoises (Neophocaena phocaenoides) were examined, and abnormalities of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase and gamma glutamyltransferase were determined in a male finless porpoise. The numbers of white and red blood cells in pregnant female porpoises were significantly lower than those in nonpregnant ones (P<0.05). Significantly higher values of serum creatinine were observed in summer when compared with the values in winter (P<0.01). Abnormalities of hepatic enzymes could improve with administration of ursodeoxycholic acid and a hepatic hydrolysate drug. PMID- 22673748 TI - Preliminary study for a newly designed silicone stent and delivery system for canine obstructive tracheal disease. AB - The goal of this study was to prove the possibility of using silicone stents broadly used for human medicine in canine obstructive tracheal disease. A silicone stent anatomically designed for canine trachea was tested on 5 beagle dogs for 8 weeks. The stent was carefully inserted using a newly developed delivery device under fluoroscopic guidance. There were no technical difficulties in placing the stent during the procedure. Previously reported complications of airway stenting such as stent migration or granulation tissue formation did not occur in any of the cases. In addition, removal of the stent was as simple as inserting it, and complications were absent. The stent introduced in this study could possibly be applied to various canine obstructive tracheal diseases. PMID- 22673749 TI - Establishment of hamster cell lines with EGFP-tagged human XRCC4 and protection from low-dose X-ray radiation. AB - In clinical settings, cellular resistance to chemotherapy and radiotherapy is a significant component of tumor treatment failure. The mechanisms underlying the control of localization of DNA repair proteins play a key role in the regulation of DNA repair activity. The DNA repair protein XRCC4, which is a regulator of DNA ligase IV activity, might be a key contributor to not only chemoresistance to anticancer agents, e.g., etoposide, but also radioresistance. However, it remains unclear whether XRCC4, which is a key player in nonhomologous DNA-end-joining (NHEJ), plays a role in low-dose radioresistance. In this study, we confirmed that human XRCC4 tagged with the enhanced green fluorescent protein (EGFP-XRCC4), as well as the DNA damage sensor Ku80 tagged with EGFP, mainly localized in the nuclei and its accumulation at DNA damaged sites began immediately after microirradiation. Moreover, we generated and characterized cell lines expressing EGFP-XRCC4 in XRCC4-deficient cells, i.e., XR-1 cells derived from the Chinese hamster ovary. Our findings showed that XR-1 cells were more sensitive than controls (CHO-K1) to low-dose X-irradiation (<0.5 Gy), whereas the radiosensitive phenotype of XR-1 cells was rescued by the expression of EGFP-XRCC4. We also confirmed that EGFP-XRCC4 expressed stably in XR-1 cells stabilizes DNA ligase IV. Altogether, these cell lines might be useful for the study of not only the dynamics and function of XRCC4, but also the molecular mechanism underlying the cellular resistance via the NHEJ pathway to low-dose radiation in mammalian cells. PMID- 22673750 TI - Risk factors for multiple myeloma: a hospital-based case-control study in Northwest China. AB - BACKGROUND: The distinctive racial/ethnic and geographic distribution of multiple myeloma (MM) suggests that both family history and environmental factors may contribute to its development. METHODS: A hospital-based case-control study consisting of 220 confirmed MM cases and 220 individually matched patient controls, by sex, age and hospital was carried out at 5 major hospitals in Northwest China. A questionnaire was used to obtain information on demographics, family history, and the frequency of food items consumed. RESULTS: Based on multivariate analysis, a significant association between the risk of MM and family history of cancers in first degree relatives was observed (OR=4.03, 95% CI: 2.50-6.52). Fried food, cured/smoked food, black tea, and fish were not significantly associated with the risk of MM. Intake of shallot and garlic (OR=0.60, 95% CI: 0.43-0.85), soy food (OR=0.52, 95% CI: 0.36-0.75) and green tea (OR=0.38, 95% CI: 0.27-0.53) was significantly associated with a reduced risk of MM. In contrast, intake of brined vegetables and pickle was significantly associated with an increased risk (OR=2.03, 95% CI: 1.41-2.93). A more than multiplicative interaction on the decreased risk of MM was found between shallot/garlic and soy food. CONCLUSION: Our study in Northwest China found an increased risk of MM with a family history of cancer, a diet characterized by low consumption of garlic, green tea and soy foods, and high consumption of pickled vegetables. The effect of green tea in reducing the risk of MM is an interesting new finding which should be further confirmed. PMID- 22673751 TI - [Invasive aspergillosis in a pediatric hematology-oncology ward]. PMID- 22673752 TI - Saliva in Prader-Willi syndrome: quantitative and qualitative characteristics. AB - OBJECTIVE: To evaluate salivary flow rates and assess whole salivary total protein, MUC7 and cystatin in individuals with Prader-Willi syndrome (PWS) compared with healthy controls. DESIGN: The participants were forty-eight individuals with PWS (mean age 20.2 +/- 9.5) and an age- and sex-matched control group. Flow rates of unstimulated whole saliva (UWS), stimulated whole saliva (SWS), submandibular/sublingual (SS), and parotid saliva (PS) were recorded (ml/min) and unstimulated whole saliva used for further protein analysis. Total protein concentration was determined via the bicinchoninic acid method, and MUC7 and cystatin levels via a Dot Blot. RESULTS: Mean UWS (0.12 +/- 0.11 vs. 0.32 +/- 0.20, p<0.001), SWS (0.41 +/- 0.35 vs. 1.06 +/- 0.63, p<0.001) and SS (0.27 +/- 0.19 vs. 0.50 +/- 0.29, p<0.001) salivary flow rates were significantly lower in PWS compared with controls. No significant difference was found in PS flow rate between the two groups. The mean total protein concentration (mg/ml) was 3.19 +/- 3.04 in PWS compared with 1.32 +/- 1.11 in controls (p<0.001). Median concentration of MUC7 (mg/ml) was 1.29 (0.11-10.85) in the PWS group, and 0.39 (0.03-2.22) in the control group (p<0.001). No significant difference was found in cystatin concentration between the groups. The output of proteins did not differ significantly between PWS and controls. CONCLUSION: With the exception of parotid saliva, salivary flow rates were lower among individuals with PWS than in their matched controls. Saliva protein concentrations in UWS were high compared with the healthy group, although the protein output did not differ significantly. PMID- 22673753 TI - Diagnostic performance of labial minor salivary gland flow measurement for assessment of xerostomia. AB - OBJECTIVE: Minor salivary gland flow rate (MF) has been proposed as a key feature of xerostomia (subjective feeling of dry mouth). To assess its diagnostic performance, MF was compared in xerostomia and control subjects. DESIGN: Sixty six subjects with xerostomia and 30 controls were enrolled. MF was measured in the lower labial mucosa using the iodine-starch filter paper method. Stimulated whole salivary flow rates were also measured using the gum test (stimulated-WF). RESULTS: Both labial-MF and stimulated-WF were significantly lower in xerostomia subjects than in controls. There was a positive correlation between labial-MF and stimulated-WF in control but not xerostomia subjects. In xerostomia subjects compared to controls, there was a significantly larger reduction in labial-MF than in stimulated-WF. Xerostomia was most accurately diagnosed using a labial-MF cutoff value of 0.25 MUL/cm(2)/min. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy at this cutoff value were 1.00, 0.87, 0.93, 1.00, and 0.96, respectively. Compared to respective values of 0.64, 1.00, 1.00, 0.56, and 0.75 for stimulated-WF at the traditional cutoff of 1.0 mL/min, these data indicate the higher sensitivity, negative predictive value, and diagnostic accuracy of labial-MF. CONCLUSIONS: Xerostomia was more strongly related to reduction of labial-MF than to that of stimulated-WF. Xerostomia was most likely triggered at a labial-MF cut-off value of 0.25 MUL/cm(2)/min based on results from the iodine-starch method. PMID- 22673754 TI - Bacterial viability on surface-modified resin-based dental restorative materials. AB - The purpose of the present investigation was to investigate the viability of early colonizers on the surfaces of resin-based dental restorative materials modified with low-surface tension active agents in comparison with the unmodified material. A novel polymeric sorption material, loaded with two low-surface tension gamma(L) active agents (hydroxyfunctional polydimethylsiloxane and polydimethylsiloxane) or a polymerizable active agent (silicone polyether acrylate), was used to modify commonly formulated experimental dental resin composites. The non-modified resin was used as the standard (ST). The viability of Actinomyces naeslundii, Actinomyces viscosus, Streptococcus mitis, Streptococcus oralis, and Streptococcus sanguinis on water-stored, polished, and human saliva pellicle-coated specimens was determined using a fluorescence microscope after 8 and 24h. Total, vital, and non-vital cells were calculated from the microscopic images by counting pixels per colour. Means, standard deviations, univariate ANOVA and multiple comparisons with post hoc Scheffe's tests were calculated. t-Test was done to compare 8-h and 24-h bacteria counts. For all tests p<0.05 was chosen. NULL HYPOTHESIS: the test materials and the standard did not differ either in the total bacterial counts or in the respective bacterium's viability after 8 or 24h. The test materials modified with the silicone polyether acrylate showed lower total bacteria count after 8 or 24h than ST. But all test materials had significantly fewer vital cells after 8 or 24h compared to ST. The contact angle did not influence bacterial adhesion, but low total SFE and a low polar term of SFE resulted in fewer bacteria. The material's chemistry also affected the total and vital cell counts. Different bacteria viabilities needed to be explored to obtain relevant information regarding bacterial adhesion on dental composite resins. The novel sorption material loaded with low gamma(L) active agents or with a low gamma(L) polymerizable silicone polyether acrylate used to modify the chemistry of the test materials was appropriate to reduce bacterial adhesion or cell viability, respectively. PMID- 22673755 TI - Finite element analysis suggests functional bone strain accounts for continuous post-eruptive emergence of teeth. AB - OBJECTIVE: To explore the possible role of functional stress in driving continuous post-eruptive emergence of teeth. DESIGN: A two dimensional finite element analysis model was established with a single mandibular premolar subjected to sagittal bending. Equivalent strain was charted for the inner and outer surfaces of the lamina dura, because bone deposition and resorption of this structure is confined to surface osteoblasts and osteoclasts. Bone disuse resorption was assumed to take place at equivalent strain values below 0.0008, while deposition was above 0.002. Strain in the periodontal ligament and principal stress throughout the model were also characterized. RESULTS: Strain analysis indicated bone maintenance for the lamina dura throughout most of the root length, but in both the apical and upper root regions, resorption was predicted for the outer surface, and bone deposition was predicted for the inner surface of the lamina dura. Strain in the periodontal ligament varied little with the exception of a marked increase close to the crown. Principal stress analysis revealed compression of the lower model border, with areas of increasing tension towards the upper model border. CONCLUSIONS: Strain from functional forces may continuously drive post-eruptive emergence of teeth through bony remodelling of the lamina dura, lifting teeth by both raising the apical lamina dura, and narrowing the upper root space to accommodate tapering root form. Such strain driven bone turnover may contribute to pre-eruptive movement of teeth. PMID- 22673757 TI - Timing of hepatitis B vaccination and impact of non-simultaneous vaccination with DTP vaccine following introduction of a hepatitis B birth dose in the Philippines. AB - Timely administration of hepatitis B vaccine beginning at birth prevents up to 95 per cent of perinatally acquired hepatitis B virus infections in infants of infected mothers. The Philippines changed its national HepB schedule in 2007 to include a dose at birth. We evaluated vaccination schedule change by reviewing infant records at selected health facilities to measure completeness and timeliness of HepB administration and frequency of recommended, simultaneous vaccination with diphtheria-tetanus-pertussis (DTP) vaccine. Of 1431 sampled infants, 1106 (77 per cent) completed the HepB series and 10 per cent followed the national schedule. The proportion with timely vaccination declined with successive doses: HepB1 (71 per cent), HepB2 (47 per cent), and HepB3 (26 per cent). Twentysix per cent received HepB2 simultaneously with DTP1 and 34 per cent received HepB3 simultaneously with DTP3. If HepB and DTP vaccination were given simultaneously,10 per cent more infants could have received all HepB doses. Program implementers should monitor vaccination timeliness and increase simultaneous administration to improve vaccination coverage and decrease disease incidence. PMID- 22673758 TI - Modeling sickle hemoglobin fibers as one chain of coarse-grained particles. AB - Sickle cell disease (SCD) is caused by a single point mutation in the beta-chain hemoglobin gene, resulting in the presence of abnormal hemoglobin S (HbS) in the patients' red blood cells (RBCs). In the deoxygenated state, the defective hemoglobin tetramers polymerize forming stiff fibers which distort the cell and contribute to changes in its biomechanical properties. Because the HbS fibers are essential in the formation of the sickle RBC, their material properties draw significant research interests. Here, a solvent-free coarse-grain molecular dynamics (CGMD) model is introduced to simulate single HbS fibers as a chain of particles. First, we show that the proposed model is able to efficiently simulate the mechanical behavior of single HbS fibers. Then, the zippering process between two HbS fibers is studied and the effect of depletion forces is investigated. Simulation results illustrate that depletion forces play a role comparable to direct fiber-fiber interaction via Van der Waals forces. This proposed model can greatly facilitate studies on HbS polymerization, fiber bundle and gel formation as well as interaction between HbS fiber bundles and the RBC membrane. PMID- 22673759 TI - Evaluating the properties of the coefficient of multiple correlation (CMC) for kinematic gait data. AB - When assessing reliability of three dimensional gait analysis, the coefficient of multiple correlation (CMC), a measure of similarity of waveforms, is frequently used. Several shortcomings of the method have been reported. It is strongly related to the range of motion (ROM); it is supposed to take values from 0 to 1, but is known to obtain complex values and break down. Removing offset before calculations appears to make it insensitive to apparent differences in gait. In the present work we use stochastic simulations to demonstrate why all of this happens, and the consequences thereof. We also demonstrate other, lesser-known, issues with the method, such as the strong dependency on number of subjects and test situations. The results are demonstrated on real data from an inter-rater repeatability study. We conclude that the CMC in its current form is generally unsuitable as a tool for assessing reliability in kinematic gait data. PMID- 22673760 TI - An evaluation of anatomical and functional knee axis definition in the context of side-cutting. AB - Side-cutting is commonly used to evaluate knee joint kinematics and kinetics in the context of anterior cruciate ligament injury risk. Many existing side-cutting studies fail to clearly define the orientation of the femoral frame and the knee axis, making comparisons between studies difficult. A femoral frame constructed using the ISB or existing functional methods does not necessarily have a medial lateral axis that is aligned with the axis of the knee. A functional frame that directly aligns with the medial-lateral knee axis was compared to the ISB anatomical frame and the Besier functional frame (Besier et al., 2003) to determine whether the chosen frame would affect the interpretation of side cutting data. Kinematic and kinetic variables were calculated during three side cutting manoeuvres of 28 subjects. Differences in mean frame orientation were correlated with the differences in mean knee angle during side-cutting. The differences between the ISB anatomical frame and the functional frames were significantly correlated with the differences in superior-inferior and medial lateral axis orientations. Coefficients of multiple correlation showed a good to high (CMCs>=0.74) similarity between frames for knee angles and moments. Using a femoral anatomical frame rather than a functional frame most significantly affected offset rather than cross talk in knee angles and moments measured during side-cutting. There were no significant differences in offset or cross talk between the two functional methods. Maximum differences of <4 degrees for frontal plane knee angle requires cautious interpretation but differences <8Nm for knee joint moment were not thought to affect the interpretation of side cutting data when comparing between studies. PMID- 22673761 TI - Potent oxidative DNA cleavage by the di-copper cytotoxin: [Cu2(MU terephthalate)(1,10-phen)4]2+. AB - The di-copper(II) cation, [Cu(2)(MU-terephthalate)(1,10-phen)(4)](2+), is a powerful, non-sequence-specific, minor-groove oxidizer of duplex DNA which, unlike copper(II) bis-1,10-phenanthroline chloride, operates independently of exogenous reagents. The agent displays excellent in vitro cytoxicity towards cisplatin-resistant ovarian cancer cells, producing intracellular reactive oxygen species upon nano-molar exposure. PMID- 22673762 TI - Breaking bad news: a phenomenological exploration of Irish nurses' experiences of caring for patients when a cancer diagnosis is given in an acute care facility (part 1). AB - BACKGROUND: The focus of this article is on the meanings attributed by nurses who worked with patients receiving a cancer diagnosis within acute care settings in Ireland. OBJECTIVE: The aim of this article was to explore the nurses' perceptions of caring for patients who receive bad news in the form of a cancer diagnosis while in an acute care setting. METHODS: The article focuses on the perceptions of 20 nurses who formed the nurse participant group in a larger phenomenological study exploring giving and receiving a cancer diagnosis. Data were collected using unstructured in-depth interviews. Analysis was conducted using Koch's analytical framework. RESULTS: The nurses' narratives provided 2 emerging themes entitled, "connectedness: journeying as professional within the everyday world" and "connectedness: exclusion of professional within the everyday world." This article focuses on the first emerging theme and highlights the experiences of nurses as they reflect on their interactions with their patients before, during, and after the giving of a cancer diagnosis. CONCLUSIONS: This study highlights the importance of professional companionship. It provides insights into the nurse-patient challenges as a result of lack of information. IMPLICATIONS FOR PRACTICE: Lack of information and involvement affects the nurse's ability to be authentically present for the recipient and results in a fracture to the nurse-patient relationship. Understanding the experiences of nurses from acute care settings where the cancer diagnosis is often given will inform and enable the nurse working in oncology settings to engage patients in a more meaningful and focused way. PMID- 22673763 TI - Evaluation of health risk and arsenic levels in vegetables sold in markets of Dhaka (Bangladesh) and Salamanca (Spain) by hydride generation atomic absorption spectroscopy. AB - The main objective of this study was to determine arsenic (As) levels in vegetables collected from the markets of Dhaka, Bangladesh and for comparison from Salamanca, Spain by HGAAS under optimal conditions, and the potential health risk from consumption of these vegetables. The mean and range of the total As concentration in the vegetables from the markets of Dhaka, Bangladesh were 114 and 1.0-293 MUg/kg, respectively. Total As concentration in 77% of Bangladesh vegetables measured was higher than that recommended by the standard. The mean and range of As concentrations for vegetables grown in Spain were 65 and bdl-130 MUg/kg, respectively, for Salamanca, 102 and bdl-423 MUg/kg, respectively, for Almeria. The As content of the Bangladesh vegetables was approximately twofold to threefold higher than those observed for the vegetables from Almeria and Salamanca (Spain), but in some cases, were similar or less. Daily consumption of As-rich vegetables may result in an additional source of As in the diet, based on the provisional tolerable intake of As for adults recommended by WHO. PMID- 22673764 TI - Selected morphological changes in Artemia franciscana after ionizing radiation exposure. AB - Nauplii of Artemia franciscana were irradiated by the doses of 0.25, 0.5, 1.0, and 2.5 kGy (60)Co. Dimensions of the body length, body width, intestine width, intestine epithelium width, and intestine lumen width, as well as the mutual ratios of dimensions were determined in 126 specimens. Ratios of the body length/body width (3.98, 3.60, 3.59, and 3.45 vs. 4.13 of control group), and ratios of the intestine epithelium width/intestine lumen width (0.64, 0.52, 0.51, and 0.45 vs. 0.85 of control group), according to the doses, were the most important parameters of evaluation of dependence of morphological changes on radiation doses. PMID- 22673765 TI - Biochemical effects of veterinary antibiotics on proliferation and cell cycle arrest of human HEK293 cells. AB - The purpose of this study was to examine the effects of veterinary antibiotics, including amoxicillin (AMX), chlortetracycline (CTC) and tylosin (TYL), on the biochemical mechanism of human embryonic kidney cells (HEK293). CTC and TYL inhibited HEK293 cell proliferation, in both time- and dose-dependent manners, and changed the cell morphology; whereas, AMX showed no cytotoxic effects. The cell cycle analysis of CTC and TYL revealed G1-arrest in HEK293 cells. Western blot analysis also showed that CTC and TYL affected the activation of DNA damage responsive proteins, as well as cell cycle regulatory proteins, such as p53, p21(Waf1/Cip1) and Rb protein, which are crucial in the G1-S transition. The activation of p21(Waf1/Cip1) was significantly up-regulated over time, but there was no change in the level of CDK2 expression. The results of this study suggest that veterinary antibiotics, even at low level concentrations on continuous exposure, can potentially risk the development of human cells. PMID- 22673766 TI - Overexpression of 3beta-hydroxysteroid dehydrogenases/C-4 decarboxylases causes growth defects possibly due to abnormal auxin transport in Arabidopsis. AB - Sterols play crucial roles as membrane components and precursors of steroid hormones (e.g., brassinosteroids, BR). Within membranes, sterols regulate membrane permeability and fluidity by interacting with other lipids and proteins. Sterols are frequently enriched in detergent-insoluble membranes (DIMs), which organize molecules involved in specialized signaling processes, including auxin transporters. To be fully functional, the two methyl groups at the C-4 position of cycloartenol, a precursor of plant sterols, must be removed by bifunctional 3beta-hydroxysteroid dehydrogenases/C-4 decarboxylases (3betaHSD/D). To understand the role of 3betaHSD/D in Arabidopsis development, we analyzed the phenotypes of knock-out mutants and overexpression lines of two 3betaHSD/D genes (At1g47290 and At2g26260). Neither single nor double knock-out mutants displayed a noticeable phenotype; however, overexpression consistently resulted in plants with wrinkled leaves and short inflorescence internodes. Interestingly, the internode growth defects were opportunistic; even within a plant, some stems were more severely affected than others. Endogenous levels of BRs were not altered in the overexpression lines, suggesting that the growth defect is not primarily due to a flaw in BR biosynthesis. To determine if overexpression of the sterol biosynthetic genes affects the functions of membrane-localized auxin transporters, we subjected plants to the auxin efflux carrier inhibitor, 1-N naphthylphthalamic acid (NPA). Where-as the gravity vectors of wild-type roots became randomly scattered in response to NPA treatment, those of the overexpression lines continued to grow in the direction of gravity. Overexpression of the two Arabidopsis 3betaHSD/D genes thus appears to affect auxin transporter activity, possibly by altering sterol composition in the membranes. PMID- 22673768 TI - Impact of glycemic variability on cardiovascular outcomes beyond glycated hemoglobin. Evidence and clinical perspectives. AB - AIMS: The aim of this review is to focus on intra-day glucose variability (GV), specifically reviewing its correlation with HbA1c, the methods currently available to measure it, and finally the relationship between GV and cardiovascular outcomes, in type 1 and type 2 diabetic patients, and in the non diabetic population. DATA SYNTHESIS: The term GV has been used in the literature to express many different concepts; in the present review, we focus our attention on intra-day GV. In particular, we try to assess whether GV provides additional information on glycemic control beyond HbA1c, since GV seems to be incompletely expressed by HbA1c, particularly in patients with good metabolic control. Many different indexes have been proposed to measure GV, however at the moment no "gold standard" procedure is available. Evidence in vitro, in experimental settings and in animal studies, shows that fluctuating glucose levels display a more deleterious effect than constantly high glucose exposure. However, these findings are not completely reproducible in human settings. Moreover, the relationship between GV and cardiovascular events is still controversial. CONCLUSIONS: The term GV should be reserved to indicate intra-day variability and different indexes of GV should be used, depending on the metabolic profile of the population studied and the specific issue to be investigated. Self glucose monitoring or continuous glucose monitoring should be used for assessing glucose variability. PMID- 22673767 TI - Association of grey matter volume deviation with insight impairment in first episode affective and non-affective psychosis. AB - The neurobiological correlates of impaired insight in psychotic illness remain uncertain and may be confounded by factors such as illness progression and medication use. Our study consisted of two separate experiments. In the first experiment, we examined the association between measures of insight and regional brain volume in thirty-two patients with first-episode psychosis. In the second experiment, we looked at similar associations in thirty individuals with chronic schizophrenia. Detailed measures of symptom awareness and symptom attribution were obtained using the Scale to assess Unawareness of Mental Disorder. MRI scans were acquired and analysed using Statistical Non-Parametric Mapping for voxel based analyses of grey matter maps. Regression models were used to assess the relationship between insight and grey matter volume in both the first-episode psychosis and the chronic schizophrenia experiments whilst controlling for potential confounds. In first-episode psychosis patients, symptom misattribution was associated with increased grey matter in the right and left caudate, right thalamus, left insula, putamen and cerebellum. In the chronic schizophrenia study, there were no significant associations between regional grey matter volume and measures of insight. These findings suggest that neuroplastic changes within subcortical and frontotemporal regions are associated with impaired insight in individuals during their first episode of psychosis. PMID- 22673769 TI - Vitamin D status, incident diabetes and prospective changes in glucose metabolism in older subjects: the Hoorn study. AB - BACKGROUND AND AIMS: Vitamin D deficiency may contribute to impaired glucose metabolism and type 2 diabetes, especially in the elderly population. We aimed to evaluate whether baseline 25-hydroxyvitamin D (25[OH]D) levels are prospectively associated with deterioration of glucose metabolism and the incidence of diabetes. METHODS AND RESULTS: We examined a subsample from the population based Hoorn study among older men and women. Physical examinations were performed from 2000 to 2001 and included measurements of 25(OH)D. Glucose tolerance tests and HbA1c measurements were performed at baseline and at a follow-up between 2007 and 2009. We included 351 study participants (51% females; 67.9 +/- 5.7 years). Baseline 25(OH)D levels were 56.7 +/- 18.8 nmol/L and follow-up visits were performed after 7.5 +/- 0.5 years. Among 280 study participants without diabetes at baseline we recorded 45 cases of incident diabetes. There was no significant association of 25(OH)D with the incidence of diabetes and with fasting and 2h postload glucose levels at follow-up. In analyses adjusted for age, sex, and baseline HbA1c there was, however, a significant association of 25(OH)D with follow-up HbA1c levels (beta coefficient=-0.085, p=0.085). This association was attenuated after further adjustments for BMI (beta coefficient=-0.079, p=0.064). CONCLUSIONS: In this study among the older population we observed no significant association of baseline 25(OH)D with glucose metabolism and incident diabetes. We found, however, a non-significant trend towards an inverse association of 25(OH)D with prospective changes in HbA1c that deserves further investigations. PMID- 22673770 TI - Bolus calculator improves long-term metabolic control and reduces glucose variability in pump-treated patients with Type 1 diabetes. PMID- 22673771 TI - Anastomosis of endothelial sprouts forms new vessels in a tissue analogue of angiogenesis. AB - Here we describe a microfluidic device that accurately reproduces the dynamics of vascular anastomosis, the process by which vascular sprouts connect to achieve perfusion during angiogenesis. The micro-device features two parallel endothelial cell-lined vessel analogues separated by a 300 MUm wide collagenous matrix into which the vessels can sprout and form perfused bridging connections. By accurately recapitulating anastomosis in vitro, the device will enable a new generation of studies of the mechanisms of angiogenesis and provide a novel and practical platform for drug screening. PMID- 22673772 TI - Localization of alphavbeta3-like integrin in cultivated larval cells of the mussel Mytilus trossulus during neuronal and muscle differentiation. AB - Using immunofluorescence phenotyping, the expression of alphavbeta3-like integrin was examined during neuronal and muscle differentiation in cell cultures derived from trochophore larvae of the mussel Mytilus trossulus. We have demonstrated that some mussel cells grown on fibronectin in vitro express the extracellular matrix (ECM) alphavbeta3 integrin-like receptor. At the same time, the distribution of alphavbeta3-like integrin is not ubiquitous, i.e. it depends on the cell type and the time of cultivation. Using immunohistochemical staining, we have found that only in some cells this integrin is co-localized with molluscan neuronal markers, neurotransmitters serotonin (5-HT) or Phe-Met-Arg-Phe-NH(2) neuropeptide (FMRFamide), and also with filament actin but not with paramyosin. Although we have previously shown that an integrin-dependent mechanism is involved in cell adhesion and differentiation of muscle cells of Mytilus, in this study, alphavbeta3-like integrin has not been found to participate in fibronectin adhesion of muscle cells but may be a linking agent between the ECM and the neuron-like cells. PMID- 22673774 TI - Imaging study of ossifying fibroma with associated aneurysmal bone cyst in the paranasal sinus. AB - OBJECTIVE: To determine the CT and MR imaging features of ossifying fibroma with aneurysmal bone cyst of the paranasal sinus. MATERIALS AND METHODS: We retrospectively reviewed 15 patients with histopathology-proven ossifying fibromas with aneurysmal bone cysts in the paranasal sinus. All 15 patients underwent CT and MR imaging. The following imaging features were reviewed: location, shape, margin, CT findings, and MR imaging appearances and time intensity curve of dynamic contrast-enhanced MR imaging. RESULTS: Ossifying fibromas occurred in the maxillary sinus in one patient, sphenoid sinus in 2, frontal sinus in 3, frontoethmoid sinuses in 3, and ethmoid sinus in 6 patients. Ossifying fibromas showed an elliptic-shape and aneurysmal bone cysts revealed a multicystic appearance, with well-demarcated margins. On unenhanced CT, ossifying fibromas appeared isodense to gray matter with scattered calcifications in nine, ground-glass appearance in 6 patients and aneurysmal bone cysts showed mixed density. Ossifying fibromas appeared isointense to gray matter in 12 and slightly hypointense in three patients on T1-weighted images, and isointense in 4 and hypointense in eleven patients on T2-weighted images, with moderate or marked enhancement after administration of contrast material. The time-intensity curves of eight ossifying fibromas exhibited a rapidly enhancing and rapid washout pattern. The intracystic components of aneurysmal bone cysts showed heterogeneous signal intensity on MR images, with fluid-fluid levels identified clearly by T2 weighted images, without enhancement. The periphery and septa of aneurysmal bone cysts appeared isointense on MR images, with marked enhancement. CONCLUSIONS: Fluid-fluid levels within an elliptic-shape mass with scattered calcifications or ground-glass appearance is highly suggestive of this complicated entity in the paranasal sinus. PMID- 22673773 TI - Improved quality of life following total pancreatectomy and auto-islet transplantation for chronic pancreatitis. AB - BACKGROUND: Total pancreatectomy (TP) with auto-islet transplant (AIT) is an extreme treatment for chronic pancreatitis, and we reviewed our experience to assess the impact on quality of life (QOL). METHODS: A prospective cohort study from 2007 through 2010 with pre- and postoperative assessments of the Depression Anxiety Stress Scale, Pain Disability Index, and visual analogue pain scale was performed. RESULTS: Twenty patients underwent TP-AIT with a median follow-up of 12 months (6.75-24 months). All patients reported moderate (45 %) to severe (55 %) pain prior to surgery. TP-AIT resulted in significant decreases in abdominal pain (p < 0.001), 80 % reporting no or mild pain. Despite pain improvement, only 30 % discontinued narcotics. Improvements in all PDI QOL domains improved from 79 to 90 % (p = 0.002), with greatest improvements seen in those without prior pancreatic surgery, younger patients, and in those with higher levels of preoperative pain. Patients were less affected by depression and anxiety prior to surgery, but 60 and 70 % did show improvement in depression and anxiety, respectively (p = 0.033). Sixteen patients (80 %) required exogenous insulin at last follow-up (mean total dose of insulin 11.6 U/day). CONCLUSIONS: TP-AIT significantly improves pain and QOL measures in appropriately selected patients with CP. PMID- 22673775 TI - Treatment of hepatocellular carcinoma adjacent to large blood vessels using 1.5T MRI-guided percutaneous radiofrequency ablation combined with iodine-125 radioactive seed implantation. AB - OBJECTIVE: The objective is to study the technology associated with and feasibility of the treatment of hepatocellular carcinoma (HCC) adjacent to large blood vessels using 1.5 T MRI-guided radiofrequency ablation combined with iodine 125 (I-125) radioactive seed implantation. METHODS: Sixteen patients with a total of 24 HCC lesions (average maximum diameter: 2.35+/-1.03 cm) were pathologically confirmed by biopsy or clinically diagnosed received 1.5 T MRI-guided percutaneous radiofrequency ablation (RFA) treatment. Each patient had one lesion adjacent to large blood vessels (>=3 mm); after the ablation, I-125 radioactive seeds were implanted in the portions of the lesions that were adjacent to the blood vessels. RESULTS: All the ablations and I-125 radioactive seed implantations were successful; a total of 118 seeds were implanted. The ablated lesions exhibited hypointense signals on the T2WI sequence with a thin rim of hyperintense signals; they also exhibited significant hyperintense signals on the T1WI sequence with clear boundaries. The average follow-up period was 11.1+/-6.2 months. There were 23 complete responses and one partial response in the 24 lesions. The alpha-fetoprotein (AFP) levels of the patients significantly decreased. CONCLUSION: The 1.5 T MRI-guided RFA combined with I-125 radioactive seed implantation for the treatment of HCC adjacent to large blood vessels is an effective technology. PMID- 22673776 TI - Hypovascular hepatic nodule showing hypointensity in the hepatobiliary phase of gadoxetic acid-enhanced MRI in patients with chronic liver disease: prediction of malignant transformation. AB - PURPOSE: To investigate the predictive factors of malignant transformation of hypovascular hepatic nodule showing hypointensity in the hepatobiliary phase images of gadoxetic acid-enhanced MRI (HHN). MATERIALS AND METHODS: The clinical data and imaging findings of dynamic contrast-enhanced computed tomography (DCE CT) and gadoxetic acid-enhanced MRI for a total of 103 HHNs in 24 patients with chronic liver disease were retrospectively investigated. After the results of follow-up examinations were investigated, HHNs were categorized into the three groups for each comparison: (1) nodules with enlargement and/or vascularization and others, (2) nodules with only enlargement and others, (3) nodules with only vascularization and others. Enlargement and/or vascularization during the follow up period were defined as malignant transformation of HHN. The frequency of each clinical datum and imaging finding in each group was compared to identify the predictive factors for malignant transformation in HHN. RESULTS: Multivariate analysis showed that a nodule size of 9 mm or more on the initial gadoxetic acid enhanced MRI was a significant predictive factor for the enlargement and/or vascularization of HHN (P<0.05). On the other hand, the hypoattenuation on the delayed phase imaging of the initial DCE-CT was a significant predictive factor for the enlargement or vascularization of HHN (P<0.05). CONCLUSION: A nodule size of 9 mm or more on the initial gadoxetic acid-enhanced MRI and hypoattenuation on the delayed phase imaging of initial DCE-CT would be helpful for predicting the outcome of HHN in patients with a risk of hepatocellular carcinoma. PMID- 22673777 TI - Bronchial wall thickness measurement in computed tomography: effect of intravenous contrast agent and reconstruction kernel. AB - Bronchial wall thickness measurements in computed tomography (CT) has become a useful tool for assessment of the severity of diseaseand the response to treatment in a large number of pulmonary diseases. However, there are only few reports evaluating its dependence on different scan protocols. The effect of intravenous contrast medium has not been analyzed. The aim of this study was to evaluate the influence of intravenous contrast medium application, the contrast phase (arterial and venous) and different reconstruction kernels on bronchial wall measurements of a newly developed algorithm. The bronchial wall thickness was analyzed in 630 bronchial sections of 56 CT examinations with dedicated software (MEVIS Airway Examiner, Fraunhofer MEVIS Bremen, Germany). Application of i.v. contrast agent significantly increased bronchial wall thickness (paired t test, p<0.001). Comparing arterial and venous phase, bronchial wall thickness was significant higher in the arterial phase (paired t-test, p=0.045). Bronchial wall thickness also increased (ANOVA with Bonferroni correction, p<0.001) when using a softer reconstruction kernel. The absolute differences in bronchial wall thickness were independent of bronchial size and generation. PMID- 22673779 TI - Higher-order genomic organization in pluripotent stem cells. AB - Recent applications of new tools for genome-wide mapping of long-range and spatial interactions have shed light onto the fundamental mechanisms of three dimensional chromatin organizations in pluripotent stem cells and their derivatives. PMID- 22673780 TI - Infections of the right hypochondrium. AB - Among the infectious diseases of the right hypochondrium, cholecystitis, cholangitis, and liver abscesses predominate. These are frequently encountered diseases, but they can still raise questions in daily practice. In this elaboration, we will thus address and illustrate: the major infectious diseases of the liver and gallbladder, and their radiological features; the potential interpretation problems and differential diagnoses; the diagnostic and therapeutic strategies used in imaging to manage infections of the right hypochondrium. PMID- 22673781 TI - Limb infections in children and adults. AB - Infections of the bone and soft tissue of the limbs need to be diagnosed and treated urgently regardless of the patient's age. Clinical features are often non specific. MRI and, in some cases, sonography investigations lead to early diagnosis and appropriate management. Computed tomography has limited value. Needle aspiration and biopsy need not be routine. In children, anatomical particularities explain the different morphological manifestations, which vary with age. It is important to both know when to propose the diagnosis of infection, so that appropriate imaging investigations are carried out, and to be aware of the symptomatology of limb infections in children and adults and understand the differential diagnoses for each age group. Clinicians should also be aware of the specific characteristics in children. PMID- 22673782 TI - Disruption of muscle renin-angiotensin system in AT1a-/- mice enhances muscle function despite reducing muscle mass but compromises repair after injury. AB - The role of the renin-angiotensin system (RAS) in vasoregulation is well established, but a localized RAS exists in multiple tissues and exerts diverse functions including autonomic control and thermogenesis. The role of the RAS in the maintenance and function of skeletal muscle is not well understood, especially the role of angiotensin peptides, which appear to contribute to muscle atrophy. We tested the hypothesis that mice lacking the angiotensin type 1A receptor (AT(1A)(-/-)) would exhibit enhanced whole body and skeletal muscle function and improved regeneration after severe injury. Despite 18- to 20-wk-old AT(1A)(-/-) mice exhibiting reduced muscle mass compared with controls (P < 0.05), the tibialis anterior (TA) muscles produced a 25% higher maximum specific (normalized) force (P < 0.05). Average fiber cross-sectional area (CSA) and fiber oxidative capacity was not different between groups, but TA muscles from AT(1A)( /-) mice had a reduced number of muscle fibers as well as a higher proportion of type IIx/b fibers and a lower proportion of type IIa fibers (P < 0.05). Measures of whole body function (grip strength, rotarod performance, locomotor activity) were all improved in AT(1A)(-/-) mice (P < 0.05). Surprisingly, the recovery of muscle mass and fiber CSA following myotoxic injury was impaired in AT(1A)(-/-) mice, in part by impaired myoblast fusion, prolonged collagen infiltration and inflammation, and delayed expression of myogenic regulatory factors. The findings support the therapeutic potential of RAS inhibition for enhancing whole body and skeletal muscle function, but they also reveal the importance of RAS signaling in the maintenance of muscle mass and for normal fiber repair after injury. PMID- 22673783 TI - Gluconeogenesis is associated with high rates of tricarboxylic acid and pyruvate cycling in fasting northern elephant seals. AB - Animals that endure prolonged periods of food deprivation preserve vital organ function by sparing protein from catabolism. Much of this protein sparing is achieved by reducing metabolic rate and suppressing gluconeogenesis while fasting. Northern elephant seals (Mirounga angustirostris) endure prolonged fasts of up to 3 mo at multiple life stages. During these fasts, elephant seals maintain high levels of activity and energy expenditure associated with breeding, reproduction, lactation, and development while maintaining rates of glucose production typical of a postabsorptive mammal. Therefore, we investigated how fasting elephant seals meet the requirements of glucose-dependent tissues while suppressing protein catabolism by measuring the contribution of glycogenolysis, glycerol, and phosphoenolpyruvate (PEP) to endogenous glucose production (EGP) during their natural 2-mo postweaning fast. Additionally, pathway flux rates associated with the tricarboxylic acid (TCA) cycle were measured specifically, flux through phosphoenolpyruvate carboxykinase (PEPCK) and pyruvate cycling. The rate of glucose production decreased during the fast (F(1,13) = 5.7, P = 0.04) but remained similar to that of postabsorptive mammals. The fractional contributions of glycogen, glycerol, and PEP did not change with fasting; PEP was the primary gluconeogenic precursor and accounted for ~95% of EGP. This large contribution of PEP to glucose production occurred without substantial protein loss. Fluxes through the TCA cycle, PEPCK, and pyruvate cycling were higher than reported in other species and were the most energetically costly component of hepatic carbohydrate metabolism. The active pyruvate recycling fluxes detected in elephant seals may serve to rectify gluconeogeneic PEP production during restricted anaplerotic inflow in these fasting-adapted animals. PMID- 22673785 TI - Airway management outside the operating room: hazardous and incompletely studied. AB - PURPOSE OF REVIEW: The review examines recent knowledge regarding techniques and complications of airway management in hospitals, outside the operating room. The review does not consider airway management at the time of cardiopulmonary resuscitation as this is a separate topic. RECENT FINDINGS: There is a relative paucity of high-quality and interventional studies with most being observational in nature. The available data confirm the high-risk nature of airway management outside the operating room. Recent studies indicate that complications, particularly in intensive care, occur more frequently after airway placement than at the time of placement. Avoidable harm due to lack of appropriate personnel, equipment and monitoring, most notably capnography, is noted. Although airway management outside the operating room remains a high-risk procedure, the optimal organizational structure, rescue procedures, algorithms and appropriate personnel have yet to be adequately defined. SUMMARY: The notably high rate of failure of primary intubation attempts and high complication rates of airway procedures create a strong argument for increased research focus in this area of high-risk and incomplete knowledge. PMID- 22673784 TI - Ghrelin increases the motivation to eat, but does not alter food palatability. AB - Homeostatic eating cannot explain overconsumption of food and pathological weight gain. A more likely factor promoting excessive eating is food reward and its representation in the central nervous system (CNS). The anorectic hormones leptin and insulin reduce food reward and inhibit related CNS reward pathways. Conversely, the orexigenic gastrointestinal hormone ghrelin activates both homeostatic and reward-related neurocircuits. The current studies were conducted to identify in rats the effects of intracerebroventricular ghrelin infusions on two distinct aspects of food reward: hedonic valuation (i.e., "liking") and the motivation to self-administer (i.e., "wanting") food. To assess hedonic valuation of liquid food, lick motor patterns were recorded using lickometry. Although ghrelin administration increased energy intake, it did not alter the avidity of licking (initial lick rates or lick-cluster size). Several positive-control conditions ruled out lick-rate ceiling effects. Similarly, when the liquid diet was hedonically devalued with quinine supplementation, ghrelin failed to reverse the quinine-associated reduction of energy intake and avidity of licking. The effects of ghrelin on rats' motivation to eat were assessed using lever pressing to self-administer food in a progressive-ratio paradigm. Ghrelin markedly increased motivation to eat, to levels comparable to or greater than those seen following 24 h of food deprivation. Pretreatment with the dopamine D1 receptor antagonist SCH-23390 eliminated ghrelin-induced increases in lever pressing, without compromising generalized licking motor control, indicating a role for D1 signaling in ghrelin's motivational feeding effects. These results indicate that ghrelin increases the motivation to eat via D1 receptor-dependent mechanisms, without affecting perceived food palatability. PMID- 22673786 TI - Pharmacogenetics in perioperative medicine. AB - PURPOSE OF REVIEW: This review will discuss the most recent developments in pharmacogenetics of commonly used perioperative medications, new collaboration networks in the field of personalized medicine, and future clinical implications of pharmacogenetics. RECENT FINDINGS: Evidence now suggests that pharmacogenetics has a role in the effects of analgesic, sedative, beta-blocker, local anesthetic, antiemetic, and obstetric medications. Variants in the MU opioid receptor gene change the analgesic effects of morphine. Additional opioids recently studied include remifentanil, methadone, tramadol, and codeine. Ibuprofen's clearance varies with CYP2C9*3 genotype. Midazolam is primarily metabolized by the CYP3A4/CYP3A5 enzymes. Enzyme induction was found to be about 50% greater with CYP3A5*3 homozygous genotype. Variations in minimum alveolar concentrations of volatile anesthetics and subcutaneous lidocaine efficacy have been attributed in part to melanocortin-1 receptor variants. Metoprolol achieved different effects in patients with CYP2D6 and beta1-receptor polymorphisms. Genetic background of the beta2-receptor contributes to susceptibility for experiencing preterm labor. The Pharmacogenomics Research Network and the Clinical Pharmacogenetics Implementation Consortium are partnerships of researchers who are dedicated to elucidating how the genome contributes to an individual patient's medication responses. SUMMARY: In the near future, pharmacogenetic approaches may facilitate personalized perioperative intervention trials. PMID- 22673787 TI - Fundamental concepts of epigenetics for consideration in anesthesiology. AB - PURPOSE OF REVIEW: Epigenetics dictate how the genetic blueprint is ultimately expressed and, therefore, is fundamental to our understanding of disease etiology and cellular responses and consequences to exposure of stimuli, such as anesthetics and perioperative stress. The goal of this review is to provide a concise overview of the fundamental concepts in epigenetics and discuss how epigenetics may be incorporated into research studies in anesthesiology. RECENT FINDINGS: Chemical modifications of DNA and core histone proteins are epigenetic marks that constitute the functional genome and are key to generating diverse cellular phenotypes from the same genotype. These modifications and the cellular machineries that regulate them are essential for maintaining tissue-specific and timing-specific expression profiles for normal functioning and can be altered in disease contexts, thus providing the molecular basis for the abnormalities. Similar to determining cellular identity within a person, epigenetic differences between individuals, including monozygotic twins, can account for disparate phenotypes in the absence of genetic variation in the genes of interest. Furthermore, epigenetic modifications are dynamic but heritable and, thus, are fitting for reinforcing adaptive phenotypes in response to external stimuli. SUMMARY: Epigenetic mechanisms underlie many human pathological conditions and impact clinical management in a variety of contexts. Although epigenetic research related to anesthesiology is sparse at the present, the full understanding of the mechanism of action of analgesics, interindividual variations in responses to anesthetics and consequences of exposure to anesthetic drugs will likely require the evaluation and integration of epigenetic information into current research paradigms. PMID- 22673788 TI - Regional anesthesia outside the operating room: indications and techniques. AB - PURPOSE OF REVIEW: Regional anesthesia is not only performed in the operating room. There are indications for the use of these techniques for pain relief in the emergency department and for anesthesia support of procedures outside the operating room. In this review, we will provide an overview of the indications for the regional techniques performed in the out-of-operating room environment. RECENT FINDINGS: In the emergency department, patients may experience significant pain, and adequate analgesia is not always provided. Regional analgesia is effective and indicated for many trauma situations including hip fracture, reduction of shoulder dislocation, treatment of upper limb fractures and multiple rib fractures.Ultrasound guidance makes the performance of regional blocks more accessible and safer for use in the emergency department setting.For therapeutic procedures outside the operating room, regional anesthesia is possible for uterine artery embolization and for postoperative analgesia after implantation of cervical brachytherapy needles. SUMMARY: Regional anesthesia is a valuable option for analgesia in trauma patients, enabling improved pain control in the emergency department and has benefits in the anesthetic management of therapeutic procedures outside the operating room. For many blocks, ultrasound guidance is useful. PMID- 22673790 TI - Infliximab therapy for familial Mediterranean fever-related amyloidosis: case series with long term follow-up. AB - Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent self-limited attacks of fever and polyserositis. Reactive amyloid A amyloidosis is the most devastating complication of FMF, and amyloidosis continues to occur in the colchicine era in untreated and noncompliant patients. Unfortunately, there is no proven effective treatment for established amyloidosis. In this report, we present four FMF-related amyloidosis patients that were treated with long term infliximab therapy with the longest duration of follow-up, together with the literature review. Infliximab was very effective in controlling gastrointestinal system findings and protracted arthritis, and it also had a favorable impact on the clinical findings of nephrotic syndrome in these patients. In conclusion, by controlling debilitating complaints of amyloidosis with infliximab, quality of life increases in these patients, and they get rid of recurrent hospitalizations and return to school or work. PMID- 22673791 TI - Sensitivity of standardised musculoskeletal examination of the hand and wrist joints in detecting arthritis in comparison to ultrasound findings in patients attending rheumatology clinics. AB - The aim of this study is to standardise the muscuoloskeletal (MSK) examination of the hand and wrist joints and to determine the sensitivity of this standard exam to diagnose arthritis in comparison to ultrasound (US) findings. A standardised approach to MSK examination of the hand and wrist joints was formulated. It consists of inspection, followed by screening exam based on active range of motion testing, and then using specific techniques to detect clinical swelling and tenderness. The scissor and squeeze techniques for metacarpophalangeal (MCP) joints, 4-finger technique for the proximal interphalangeal (PIP) joints and 2 thumb technique for the wrist joints. Patients aged 18-75 years with symptoms suggestive of inflammatory arthritis for more than 3 months were included in the study from two centres. Two rheumatologists conducted MSK examination, while a grayscale with power Doppler US was performed by two ultrasonographers recording signs of arthritis (effusion, proliferation and hyperaemia) on the same day of visit. Statistical analysis was carried out to compare MSK examination findings in detecting swelling and tenderness to US examination findings. A total of 2,112 joints were assessed both clinically and with US. Using a standard MSK examination by a rheumatologist to detect clinical swelling showed the following sensitivities as compared to US findings: 4-finger technique of 69 % in third PIP, the scissor technique of 74 % in second MCP and 70 % in third MCP, and the 2 thumb technique of 80 % at the wrist joint. The MCP squeeze technique showed sensitivity of 66 % for tenderness. A standard MSK examination with its described techniques is a sensitive tool if used appropriately to diagnose clinical arthritis as compared to US. PMID- 22673792 TI - Decreased heart rate variability in patients with psoriatic arthritis. AB - The purpose of this study was to investigate autonomous regulation of the cardiac activity by means of the heart rate variability (HRV) assessment and possible influence of conventional cardiovascular risk factors and disease activity parameters on it in patients with psoriatic arthritis (PsA). In total, 38 patients with the reliable diagnosis of PsA without clinically manifest cardiovascular pathology, known rhythm or conduction disturbances, diabetes mellitus, and hypercholesterolemia were included. In the control group, 25 age- and sex-matched healthy persons comparable with PsA patients in cardiovascular risk profile were included. For the HRV analysis, we used 5-min-long ECG records obtained at rest. Time and frequency domain parameters of HRV were calculated. Patients with PsA had decreased HRV in comparison to healthy controls as reflected by decrease of the standard deviation of normal R-R intervals (65.1 +/- 66.8 vs. 83.2 +/- 43.3 ms, respectively, p = 0.011), of the percentage of normal R-R intervals that differ by more than 50 ms (12.9 +/- 15.4 vs. 20.6 +/- 17.1 %, respectively, p = 0.035), and of the total power (2,069.4 +/- 1,537.8 vs. 2,942.5 +/- 1,734.2 ms(2), respectively, p = 0.006). A significant correlation of HRV parameters with disease duration and parameters of disease activity in PsA was found. Patients with PsA had impaired autonomous regulation of the cardiac activity, which is likely to be related to the presence of systemic inflammation and which could contribute to the increase of cardiovascular risk in this disease. PMID- 22673793 TI - Double-bundle reconstruction results in superior clinical outcome than single bundle reconstruction. AB - PURPOSE: To compare the short- and long-term clinical outcomes of the double bundle (DB) anterior cruciate ligament (ACL) reconstruction with those of single bundle (SB) ACL reconstruction. METHODS: An electronic search of the database PubMed (1966-September 2011), EMBASE (1984-September 2011), and Cochrane Controlled Trials Register (CENTRAL; 3rd Quarter, 2011) was undertaken to identify relevant studies. Main clinical outcomes were knee stability measurements including KT-1000 arthrometer measurement, Pivot shift test, and Lachman test, and clinical outcome measurements including International Knee Documentation Committee (IKDC), Lysholm knee score, Tegner activity score, and complications. RESULTS: Eighteen studies were finally included in this meta analysis, which were all classified as high risk of bias according to the Collaboration's recommended tool. It is seen that compared to SB ACL reconstruction, DB ACL reconstruction results in a KT-1000 arthrometer outcome 0.63 and 1.00 mm closer to the normal knee in a short- and long-term follow-up, respectively. Our results also reveal that DB-treated patients have a significantly higher negative rate of the pivot shift test (p < 0.00001 and = 0.006 in a short- and long-term follow-up, respectively) and Lachman test (n.s. and p < 0.0001 in a short- and long-term follow-up, respectively) compared to SB treated patients. As for the clinical outcome measurements, a significant difference is found between SB versus DB ACL reconstruction regarding the IKDC (p = 0.006 and < 0.0001 in a short- and long-term follow-up, respectively) and complications (p = 0.03), while there is no significant difference between the two groups regarding Lysholm knee score (n.s.) and Tegner activity score (n.s.). CONCLUSION: Overall, double-bundle ACL reconstruction yields better clinical outcomes when compared to single-bundle ACL reconstruction. LEVELS OF EVIDENCE: II. PMID- 22673795 TI - The effect of anticancer drugs on seven cell lines monitored by FTIR spectroscopy. AB - Systemic approaches such as metabolomics are increasingly needed to improve the development of novel drugs. In this paper, we suggest a new strategy based on infrared spectroscopy which probes the global chemical composition of a sample. Seven cell lines from three tumour types were investigated and exposed to four classical anticancer drugs belonging to two classes characterized by a unique mechanism. First, each cell line was considered separately and a hierarchical clustering was built for the seven cell lines. Spectra clustered according to the drug mechanism of action for all the cell lines tested. Second, the similarities among drug mechanism spectral fingerprints were investigated for all the cell lines simultaneously. Difference spectra (the mean spectrum of the corresponding untreated cell line was subtracted) were computed so that the particular contribution of every cell line was eliminated and only the drug-induced differences could be compared. The hierarchical clustering shows a clear tendency to distinguish the two modes of action, revealing a very similar type of response to molecules with a similar mechanism. High throughput systems with 96-well plates are now available and a well established bioassay could be developed in order to provide an objective classifier for potential anticancer drugs. PMID- 22673794 TI - The relationship between patellofemoral and tibiofemoral morphology and gait biomechanics following arthroscopic partial medial meniscectomy. AB - PURPOSE: To examine the relationship between tibiofemoral and patellofemoral joint articular cartilage and subchondral bone in the medial and gait biomechanics following partial medial meniscectomy. METHODS: For this cross sectional study, 122 patients aged 30-55 years, without evidence of knee osteoarthritis at arthroscopic partial medial meniscectomy, underwent gait analysis and MRI on the operated knee once for each sub-cohort of 3 months, 2 years, or 4 years post-surgery. Cartilage volume, cartilage defects, and bone size were assessed from the MRI using validated methods. The 1st peak in the knee adduction moment, knee adduction moment impulse, 1st peak in the knee flexion moment, knee extension range of motion, and the heel strike transient from the vertical ground reaction force trace were identified from the gait data. RESULTS: Increased knee stance phase range of motion was associated with decreased patella cartilage volume (B = -17.9 (95% CI -35.4, -0.4) p = 0.045) while knee adduction moment impulse was associated with increased medial tibial plateau area (B = 7.7 (95% CI 0.9, 13.3) p = 0.025). A number of other variables approached significance. CONCLUSIONS: Knee joint biomechanics exhibited by persons who had undergone arthroscopic partial meniscectomy gait may go some way to explaining the morphological degeneration observed at the patellofemoral and tibiofemoral compartments of the knee as patients progress from surgery. LEVEL OF EVIDENCE: III. PMID- 22673796 TI - Water-soluble ionic benzoporphyrins. AB - Novel ionic water-soluble tetrabenzoporphyrins have been successfully synthesized via a cascade reaction based on the Heck reaction. The UV-Vis spectra of these porphyrins displayed red-shifted and broadened Soret bands, and significantly enhanced Q bands. These porphyrins are highly water soluble. PMID- 22673797 TI - Slow progress in changing the school food environment: nationally representative results from public and private elementary schools. AB - BACKGROUND: Children spend much of their day in school, and authorities have called for improvements in the school food environment. However, it is not known whether changes have occurred since the federal wellness policy mandate took effect in 2006-2007. OBJECTIVE: We examined whether the school food environment in public and private elementary schools changed over time and examined variations by school type and geographic division. DESIGN AND PARTICIPANTS: Survey data were gathered from respondents at nationally representative samples of elementary schools during the 2006-2007 and 2009-2010 school years (respectively, 578 and 680 public schools, and 259 and 313 private schools). MAIN OUTCOME MEASURES: Topics assessed included competitive foods, school meals, and other food-related practices (eg, school gardens and nutrition education). A 16 item food environment summary score was computed, with possible scores ranging from 0 (least healthy) to 100 (healthiest). ANALYSES: Multivariate regression models were used to examine changes over time in the total school food environment score and component items, and variations by US census division. RESULTS: Many practices improved, such as participation in school gardens or farm to-school programs, and availability of whole grains and only lower-fat milks in lunches. Although the school food environment score increased significantly, the magnitude of change was small; as of 2009-2010 the average score was 53.5 for public schools (vs 50.1 in 2006-2007) and 42.2 for private schools (vs 37.2 in 2006-2007). Scores were higher in public schools than in private schools (P<0.001), but did not differ by race/ethnicity or school size. For public schools, scores were higher in the Pacific and West South Central divisions compared with the national average. CONCLUSIONS: Changes in the school food environment have been minimal, with much room remaining for improvement. Additional policy changes may be needed to speed the pace of improvement. PMID- 22673799 TI - Socio-economic impacts on flooding: a 4000-year history of the Yellow River, China. AB - We analyze 4000-year flood history of the lower Yellow River and the history of agricultural development in the middle river by investigating historical writings and quantitative time series data of environmental changes in the river basin. Flood dynamics are characterized by positive feedback loops, critical thresholds of natural processes, and abrupt transitions caused by socio-economic factors. Technological and organizational innovations were dominant driving forces of the flood history. The popularization of iron plows and embarkment of the lower river in the 4th century BC initiated a positive feedback loop on levee breaches. The strength of the feedback loop was enhanced by farming of coarse-sediment producing areas, steep hillslope cultivation, and a new river management paradigm, and finally pushed the flood frequency to its climax in the seventeenth century. The co-evolution of river dynamics and Chinese society is remarkable, especially farming and soil erosion in the middle river, and central authority and river management in the lower river. PMID- 22673798 TI - Kirenol exerts a potent anti-arthritic effect in collagen-induced arthritis by modifying the T cells balance. AB - Rheumatoid arthritis is characterized by the imbalance of T cells, which leads to increased pro-inflammatory and reduced anti-inflammatory cytokines. Modulating the balance among T cells is crucial for the treatment of RA. Kirenol is a major diterpenoid components of Herba Siegesbeckiae, which has been applied for arthritic therapy for centuries. Since prior research showed Kirenol exhibited anti-inflammatory effect in rats, in this study we have evaluated the effect and mechanism of bioactive Kirenol in a rat model of collagen-induced arthritis (CIA) on modulation of T cells. After immunization with bovine type II collagen (CII), Wistar rats were orally administered saline (CIA group), 2 mg/kg Kirenol or 2 mg/kg prednisolone daily for 30 days. The severity of arthritis was clinically and histologically assessed. The numbers of CD4+CD25+Foxp3+ T regulatory cells (Tregs) and IFNgamma+CD4+ and IL4+CD4+ T cells were determined by flow cytometry, the mRNA expression level of Foxp3 was quantified by RT-PCR, cytokine levels were measured by ELISA and CII-induced cell proliferation was quantified in vitro. Kirenol significantly delayed the occurrence and reduced the disease severity of CIA. Histological analysis confirmed Kirenol suppressed joint inflammation and inhibited cartilage and bone destruction, compared to the CIA group. Kirenol also upregulated the mRNA expression of Foxp3, increased the numbers of CD4+CD25+Foxp3+ and IL4+CD4+ T cells, and reduced the number of IFNgamma+CD4+ T cells. Kirenol reduced the levels of TNF-alpha, IL-17A and IL-6 in synovial fluid and TNF-alpha, IL-17A and IFN-gamma in serum, and increased the serum levels of IL-4, IL-10 and TGF-beta1. In addition, Kirenol inhibited the ability of CII to induce splenocyte, PBMC and lymph node cell proliferation in vitro, compared to cells from CIA rats. In conclusion, these results suggest that Kirenol may be a potential immunosuppressant for the treatment for rheumatoid arthritis. PMID- 22673800 TI - Fatality following a suicidal overdose with varenicline. AB - The smoking cessation agent varenicline acts as a partial agonist on alpha(4)beta(2) nicotinic acetylcholine receptors. Although debated, several reports have linked varenicline therapy to an increased risk of suicidal thoughts and/or suicide. In addition, several non-fatal overdose cases have been reported. In this report, we utilised a sample preparation procedure suitable for postmortem samples and gas chromatography coupled to mass spectrometry to analyse samples obtained from a suicidal case in which ingestion of an overdose of varenicline had occurred. Extremely high concentrations of varenicline (>250 ng/ml) were detected in the blood of the deceased, in addition to high concentrations in urine and vitreous humour. To the best of our knowledge, similar high concentrations have not been reported yet. Although, with respect to the mechanism of death in this case, confounding factors were concomitant ethanol consumption and, importantly, potentially fatal hypothermia, this is the first report of a fatality associated with the ingestion of an overdose of varenicline. PMID- 22673802 TI - A functional MRI study of multimodal selective attention following mild traumatic brain injury. AB - Previous work suggests that the ability to selectively attend to and resolve conflicting information may be the most enduring cognitive deficit following mild traumatic brain injury (mTBI). The current study used fMRI to evaluate potential differences in hemodynamic activation in 22 mTBI patients and 22 carefully matched healthy controls (HC) during a multimodal selective attention task (numeric Stroop). Behavioral data indicated faster reaction times for congruent versus incongruent trials and for stimuli presented at 0.66 compared to 0.33 Hz across both groups, with minimal differences in behavioral performance across the groups. Similarly, there were no group-wise differences in functional activation within lateral and medial prefrontal cortex during the execution of cognitive control (incongruent versus congruent trials). In contrast, within-group comparisons indicated robust patterns of attention-related modulations (ARM) within the bilateral dorsolateral prefrontal cortex and bilateral visual streams for HC but not mTBI patients. In addition, mTBI patients failed to exhibit task induced deactivation within the default-mode network (DMN) under conditions of higher attentional load. In summary, in spite of near normal behavioral performance, current results suggest within-group abnormalities during both the top-down allocation of visual attention and in regulating the DMN during the semi acute stage of mTBI. PMID- 22673805 TI - Sequence-based detection and breakpoint assembly of polymorphic inversions. AB - Inversion polymorphisms have occupied a privileged place in Drosophila genetic research since their discovery in the 1920s. Indeed, inversions seem to be nearly ubiquitous, and the majority of species that have been thoroughly surveyed have been found to be polymorphic for one or more chromosomal inversions. Despite enduring interest, however, inversions remain difficult to study because their effects are often cryptic, and few efficient assays have been developed. Even in Drosophila melanogaster, in which inversions can be reliably detected and have received considerable attention, the breakpoints of only three inversions have been characterized molecularly. Hence, inversion detection and assay design remain important unsolved problems. Here, we present a method for identification and local de novo assembly of inversion breakpoints using next-generation paired end reads derived from D. melanogaster isofemale lines. PCR and cytological confirmations demonstrate that our method can reliably assemble inversion breakpoints, providing tools for future research on D. melanogaster inversions as well as a framework for detection and assay design of inversions and other chromosome aberrations in diverse taxa. PMID- 22673807 TI - On the prospects of whole-genome association mapping in Saccharomyces cerevisiae. AB - Advances in sequencing technology have enabled whole-genome sequences to be obtained from multiple individuals within species, particularly in model organisms with compact genomes. For example, 36 genome sequences of Saccharomyces cerevisiae are now publicly available, and SNP data are available for even larger collections of strains. One potential use of these resources is mapping the genetic basis of phenotypic variation through genome-wide association (GWA) studies, with the benefit that associated variants can be studied experimentally with greater ease than in outbred populations such as humans. Here, we evaluate the prospects of GWA studies in S. cerevisiae strains through extensive simulations and a GWA study of mitochondrial copy number. We demonstrate that the complex and heterogeneous patterns of population structure present in yeast populations can lead to a high type I error rate in GWA studies of quantitative traits, and that methods typically used to control for population stratification do not provide adequate control of the type I error rate. Moreover, we show that while GWA studies of quantitative traits in S. cerevisiae may be difficult depending on the particular set of strains studied, association studies to map cis-acting quantitative trait loci (QTL) and Mendelian phenotypes are more feasible. We also discuss sampling strategies that could enable GWA studies in yeast and illustrate the utility of this approach in Saccharomyces paradoxus. Thus, our results provide important practical insights into the design and interpretation of GWA studies in yeast, and other model organisms that possess complex patterns of population structure. PMID- 22673808 TI - High-accuracy analysis system for the redox status of coenzyme Q10 by online supercritical fluid extraction-supercritical fluid chromatography/mass spectrometry. AB - The accurate profiling of oxidative stress markers is often disturbed by oxidation occurred during sample preparation. In this study, an online supercritical fluid extraction-supercritical fluid chromatography/mass spectrometry system was constructed utilizing supercritical fluid as an efficient solvent for extraction. A higher ratio of the reduced form of coenzyme Q(10) (CoQ(10)) was detected by online extraction, rather than by offline extraction using a conventional organic solvent. The results suggest that the profile of easily oxidized compounds can be acquired with high accuracy using this system because the oxidation of the target compounds during sample preparation can be avoided when using the online extraction. PMID- 22673806 TI - Genome rearrangements caused by depletion of essential DNA replication proteins in Saccharomyces cerevisiae. AB - Genetic screens of the collection of ~4500 deletion mutants in Saccharomyces cerevisiae have identified the cohort of nonessential genes that promote maintenance of genome integrity. Here we probe the role of essential genes needed for genome stability. To this end, we screened 217 tetracycline-regulated promoter alleles of essential genes and identified 47 genes whose depletion results in spontaneous DNA damage. We further showed that 92 of these 217 essential genes have a role in suppressing chromosome rearrangements. We identified a core set of 15 genes involved in DNA replication that are critical in preventing both spontaneous DNA damage and genome rearrangements. Mapping, classification, and analysis of rearrangement breakpoints indicated that yeast fragile sites, Ty retrotransposons, tRNA genes, early origins of replication, and replication termination sites are common features at breakpoints when essential replication genes that suppress chromosome rearrangements are downregulated. We propose mechanisms by which depletion of essential replication proteins can lead to double-stranded DNA breaks near these features, which are subsequently repaired by homologous recombination at repeated elements. PMID- 22673809 TI - Solid-phase extraction combined with large volume injection-programmable temperature vaporization-gas chromatography-mass spectrometry for the multiresidue determination of priority and emerging organic pollutants in wastewater. AB - In the present work the simultaneous extraction for the multiresidue determination in wastewater samples of organic compounds such as polychlorinated biphenyls (PCBs), polybrominated biphenyls (PBBs), pesticides, polycyclic aromatic hydrocarbons (PAHs), phthalate esters (PEs), alkylphenols (APs), bisphenol A (BPA) or hormones included in different lists of priority and emerging pollutants because of their action as endocrine disrupting compounds (EDCs) was developed. Different solid phase extraction (SPE) variables such as the nature of the solid phase (Oasis-HLC, C18 and Lichrolut), the sample volume, the addition of MeOH and NaCl, the pH of the water phase and the volume of the eluent solvent were optimized in order to analyze simultaneously the priority and emerging families of pollutants mentioned above. Good recoveries were obtained for Milli-Q water (80-120%), however, since the use of deuterated analogues and dilution of the sample did not correct the matrix effect, additional SPE clean-up step using Florisil(r) cartridges was necessary to obtain good results for wastewater samples (80-125%). In order to improve the limits of detection (LODs), large volume injection (LVI) using programmable temperature vaporizer (PTV) coupled to gas chromatography-mass spectrometry (GC-MS) was also optimized. Since analytes losses in the case of the most volatile congeners occurred during the derivatization step and no separation of the derivatized and the non-derivatized analytes was possible during SPE elution, two different injections were optimized for each analyte group. LODs were in good agreement with those found in the literature and relative standard deviations (RSDs) were in the 10-25% range for Milli-Q and 12-30% for wastewater samples. The method was finally applied to the determination of target analytes in three different wastewater treatment plants (WWTPs, Bakio, Gernika and Galindo (Spain)) and in one water purification plant (WPP) in Zornotza (Spain). PMID- 22673810 TI - Ionic liquids-based crosslinked copolymer sorbents for headspace solid-phase microextraction of polar alcohols. AB - Halogen-based polymeric ionic liquid (PIL) fibers, which have proved efficient for solid-phase microextraction (SPME) of polar compounds, were with very limited fiber lifetimes. In this work, a novel crosslinked PIL sorbent with satisfactory stability and durability was prepared in situ via crosslinking polymerization processes on microstructured-silver coated stainless steel wire. 1,1'-(1,6 Hexanediyl)bis(1-vinylimidazolium) bibromide ionic liquid was synthesized and used as the crosslinking agent, with 1-vinyl-3-octylimidazolium bromide as monomer. Extraction properties of the fiber for polar alcohols in polar aqueous matrix were examined using headspace SPME (HS-SPME) coupled to gas chromatography flame ionization detection (GC-FID). Under the optimized extraction and desorption conditions, the established method exhibited high extraction capacity. Wide linear ranges were obtained with correlation coefficients (R) ranging from 0.9947 to 0.9999. Limits of detection were in the range of 0.5-20 MUg L-1. Compared with the non-crosslinked PIL fiber, the proposed crosslinked PIL fiber was with higher thermal stability and durability and longer lifetime. Four different liquor beverages were analyzed as real samples and good results were obtained. PMID- 22673804 TI - Genomic variation in natural populations of Drosophila melanogaster. AB - This report of independent genome sequences of two natural populations of Drosophila melanogaster (37 from North America and 6 from Africa) provides unique insight into forces shaping genomic polymorphism and divergence. Evidence of interactions between natural selection and genetic linkage is abundant not only in centromere- and telomere-proximal regions, but also throughout the euchromatic arms. Linkage disequilibrium, which decays within 1 kbp, exhibits a strong bias toward coupling of the more frequent alleles and provides a high-resolution map of recombination rate. The juxtaposition of population genetics statistics in small genomic windows with gene structures and chromatin states yields a rich, high-resolution annotation, including the following: (1) 5'- and 3'-UTRs are enriched for regions of reduced polymorphism relative to lineage-specific divergence; (2) exons overlap with windows of excess relative polymorphism; (3) epigenetic marks associated with active transcription initiation sites overlap with regions of reduced relative polymorphism and relatively reduced estimates of the rate of recombination; (4) the rate of adaptive nonsynonymous fixation increases with the rate of crossing over per base pair; and (5) both duplications and deletions are enriched near origins of replication and their density correlates negatively with the rate of crossing over. Available demographic models of X and autosome descent cannot account for the increased divergence on the X and loss of diversity associated with the out-of-Africa migration. Comparison of the variation among these genomes to variation among genomes from D. simulans suggests that many targets of directional selection are shared between these species. PMID- 22673811 TI - Development of one-step hollow fiber supported liquid phase sampling technique for occupational workplace air analysis using high performance liquid chromatography with ultra-violet detector. AB - In this study, a simple and novel one-step hollow-fiber supported liquid-phase sampling (HF-LPS) technique was developed for enriched sampling of gaseous toxic species prior to chemical analysis for workplace air monitoring. A lab-made apparatus designed with a gaseous sample generator and a microdialysis sampling cavity (for HF-LPS) was utilized and evaluated to simulate gaseous contaminant air for occupational workplace analysis. Gaseous phenol was selected as the model toxic species. A polyethersulfone hollow fiber dialysis module filled with ethylene glycol in the shell-side was applied as the absorption solvent to collect phenol from a gas flow through the tube-side, based on the concentration distribution of phenol between the absorption solvent and the gas flow. After sampling, 20 MUL of the extractant was analyzed by high performance liquid chromatography with ultraviolet detection (HPLC-UV). Factors that influence the generation of gaseous standards and the HF-LPS were studied thoroughly. Results indicated that at 25 degrees C the phenol (2000 MUg/mL) standard solution injected at 15-MUL/min can be vaporized into sampling cavity under nitrogen flow at 780 mL/min, to generate gaseous phenol with concentration approximate to twice the permissible exposure limit. Sampling at 37.3 mL/min for 30 min can meet the requirement of the workplace air monitoring. The phenol in air ranged between 0.7 and 10 cm3/m3 (shows excellent linearity) with recovery between 98.1 and 104.1%. The proposed method was identified as a one-step sampling for workplace monitoring with advantages of convenience, rapidity, sensitivity, and usage of less-toxic solvent. PMID- 22673812 TI - Zirconia coated stir bar sorptive extraction combined with large volume sample stacking capillary electrophoresis-indirect ultraviolet detection for the determination of chemical warfare agent degradation products in water samples. AB - In this study, a sensitive, selective and reliable analytical method by combining zirconia (ZrO2) coated stir bar sorptive extraction (SBSE) with large volume sample stacking capillary electrophoresis-indirect ultraviolet (LVSS-CE/indirect UV) was developed for the direct analysis of chemical warfare agent degradation products of alkyl alkylphosphonic acids (AAPAs) (including ethyl methylphosphonic acid (EMPA) and pinacolyl methylphosphonate (PMPA)) and methylphosphonic acid (MPA) in environmental waters. ZrO2 coated stir bar was prepared by adhering nanometer-sized ZrO2 particles onto the surface of stir bar with commercial PDMS sol as adhesion agent. Due to the high affinity of ZrO2 to the electronegative phosphonate group, ZrO2 coated stir bars could selectively extract the strongly polar AAPAs and MPA. After systematically optimizing the extraction conditions of ZrO2-SBSE, the analytical performance of ZrO2-SBSE-CE/indirect UV and ZrO2-SBSE LVSS-CE/indirect UV was assessed. The limits of detection (LODs, at a signal-to noise ratio of 3) obtained by ZrO2-SBSE-CE/indirect UV were 13.4-15.9 MUg/L for PMPA, EMPA and MPA. The relative standard deviations (RSDs, n=7, c=200 MUg/L) of the corrected peak area for the target analytes were in the range of 6.4-8.8%. Enhancement factors (EFs) in terms of LODs were found to be from 112- to 145 fold. By combining ZrO2 coating SBSE with LVSS as a dual preconcentration strategy, the EFs were magnified up to 1583-fold, and the LODs of ZrO2-SBSE-LVSS CE/indirect UV were 1.4, 1.2 and 3.1 MUg/L for PMPA, EMPA, and MPA, respectively. The RSDs (n=7, c=20 MUg/L) were found to be in the range of 9.0-11.8%. The developed ZrO2-SBSE-LVSS-CE/indirect UV method has been successfully applied to the analysis of PMPA, EMPA, and MPA in different environmental water samples, and the recoveries for the spiked water samples were found to be in the range of 93.8 105.3%. PMID- 22673813 TI - A novel method for high preconcentration of ultra trace amounts of B1, B2, G1 and G2 aflatoxins in edible oils by dispersive liquid-liquid microextraction after immunoaffinity column clean-up. AB - In the present study, a new approach which uses immunoaffinity column clean-up combined with dispersive liquid-liquid microextraction (DLLME) is proposed for the preconcentration of ultra trace amounts of aflatoxins (B1, B2, G1 and G2). The aflatoxins are then determined using a high-performance liquid chromatography coupled with fluorescent detector. Samples are extracted by immunoaffinity column (IAC) clean-up, and their eluents are used as dispersants of the subsequent DLLME, for further enrichment of aflatoxins. Various parameters (the type of elution solvent, the type and volume of extraction solvent and disperser solvent, extraction time, and centrifugation time) that affect the efficiency of the two steps are optimized. Under the optimum conditions (extraction solvent: 120 MUL of chloroform, disperser solvent: 500 MUL of acetonitrile, sample pH: 7.4, centrifugation time: 3 min), the calibration for B1, B2, G1 and G2 was found to be linear with coefficient of estimation (R2) of 0.9994, 0.9976, 0.9989, 0.9973 respectively and the limit of detection (LOD) was between 1.1 * 10-4 to 5.3 * 10 3 ng mL-1 (3sigma(b)/m, n=9). The recoveries at the two spiked levels ranged from 96.0 to 110.0% and the relative standard deviation (RSD) was less than 7.8% (n=9). The results show that dispersive liquid-liquid microextraction combined with HPLC is a selective, simple, sensitive, and effective analytical method for the preconcentration and determination of ultra trace amounts of aflatoxins. The proposed method was applied for preconcentration and determination of B1, B2, G1 and G2 aflatoxin in edible oils. Analysis of aflatoxins in FAPAS test material showed that the proposed method has good accuracy. PMID- 22673814 TI - Comparison of three buffer solutions for amino acid derivatization and following analysis by liquid chromatography electrospray mass spectrometry. AB - For reversed phase separation amino acids are usually derivatized. Several derivatization reactions are carried out at basic pH. In the present work, influence of three basic buffer solutions on liquid chromatography electrospray ionization mass-spectrometric (LC-ESI-MS) analysis of amino acid derivatives was studied. Borate buffer--the most common derivatization buffer--was found to influence ESI ionization up to 23 min retention time. For 9 fluorenylmethylmethoxycarbonyl chloride (Fmoc-Cl derivatization) carbonate buffer should be preferred as it provides higher responses. Hexafluoroisopropanol (HFIP) buffer improves chromatographic peak shapes and responses for diethyl ethoxymethylenemalonate (DEEMM) derivatives. PMID- 22673815 TI - Dispersive liquid-liquid microextraction using a low density extraction solvent for the determination of 17 N-methylcarbamates by micellar electrokinetic chromatography-electrospray-mass spectrometry employing a volatile surfactant. AB - A new analytical method based on micellar electrokinetic chromatography tandem mass spectrometry (MEKC-ESI-MS/MS) employing a MS friendly surfactant (ammonium perfluorooctanoate) is proposed and validated for the identification and simultaneous quantification of 17 N-methylcarbamate pesticides in environmental and drinking water samples. MS/MS detection using an ion trap as analyzer operating in the multiple reaction monitoring mode was used. Different parameters were optimized in order to obtain an adequate CE separation combined with the highest sensitivity in MS/MS. Dispersive liquid-liquid microextraction (DLLME) using a low-density extraction solvent has been proposed for extraction, obtaining a preconcentration factor of 10. Under optimum conditions, recoveries for fortified samples ranged from 83% to 101%, with relative standard deviations lower than 8%. The limits of detection ranged from 1 to 144 ng l-1, demonstrating the sensitivity and applicability of this fast, simple, and environmentally friendly method. PMID- 22673816 TI - Preparation and characterization of molecularly imprinted polymer for di(2 ethylhexyl) phthalate: application to sample clean-up prior to gas chromatographic determination. AB - The molecularly imprinted polymer (MIP) selective for di(2-ethylhexyl) phthalate (DEHP) an environmental endocrine disruptor was prepared by suspension polymerization using methacrylamide as functional monomer and N,N'-methylene-bis acrylamide as cross-linker. The imprinted polymer was employed for solid-phase extraction of DEHP from water samples of environmental importance and characterized by FT-IR and SEM. The adsorption properties of the imprinted polymer were demonstrated by equilibrium rebinding experiments, Pseudo-second order kinetic model, Sips isotherm and Scatchard analysis. The reusability of MIP was checked for at least six repeated batch adsorption cycles and the results showed almost no deterioration in the adsorption capacity. The competitive recognition studies were performed with DEHP and structurally similar compounds; dimethyl phthalate (DMP), diethyl phthalate (DEP), and dibutyl phthalate (DBP). The imprinting factor (IF) of DEHP was found to be 12.86 which was much higher than the imprinting factors (IF) of other phthalates. A method constituted by molecularly imprinted solid-phase extraction (MISPE) with GC-FID was developed for DEHP analysis in water samples under very simple conditions. Sample loading and desorption conditions were also optimized. The MISPE method's linearity ranged from 0.035 to 3.0 MUg ml-1 with r2 = 0.9998. Intra-assay, interassay precision and accuracy ranged from 0.0168% to 1.017%, 1.130% to 4.799% and 94.98% to 99.35%, respectively. The LOD and LOQ were found to be 0.011 and 0.035 MUg ml 1, respectively. Synthesized MIP was employed in MISPE for cleaning up the spiked river water samples prior to gas chromatographic analysis. The river samples were found to contain DEHP in the range of 1.4 * 10-3 to 0.349 MUg ml-1. PMID- 22673817 TI - Adult cerebrospinal fluid does not support neurogenesis from fetal rat neural stem cells. AB - The purpose was to study the effect of human cerebrospinal fluid (CSF) on differentiation of rat neural stem cells (NSCs), and thus explore the feasibility of transplanting stem cells via lumbar puncture clinically. Rat NSCs derived from fetal brain were divided into two groups, and cultured in DMEM/F12 supplemented with 10 % FBS and human CSF, respectively. Cellular growth was observed with an inverted microscope, and immunostaining was used to analyze differentiation of NSCs in both groups. Cells of fetal brain showed shapes of spindle or star with minor sprouts at fifth day post-culture, and stained with nestin. NSCs in the control group differentiated into neurons, with positive staining to NSE, when cultured further in DMEM/F12 supplemented with 10 % FBS. While NSCs in the experiment group, cultured in CSF, differentiated into astroglia on eighth day, with positive immunostaining to GFAP. The new neurons dissolved rapidly when they were cultured in CSF. Human CSF cannot promote NSCs to differentiation toward neuron, nor support newborn neurons survival. It seems an inappropriate approach to transplant stem cells through CSF. PMID- 22673820 TI - Current world literature. PMID- 22673818 TI - The neurobiology of falls. AB - Falling is a major clinical problem; especially, in elderly population as it often leads to fractures, immobilization, poor quality of life and life-span reduction. Given the growing body of evidences on the physiopathology of balance disorders in humans, in recent years the approach of research on falls has completely changed and new instruments and new definitions have been formulated. Among them, the definition of "idiopathic faller" (i.e. no overt cause for falling in a given subject) represented a milestone in building the "science of falling". This review deals with the new determinants of the neurobiology of falling: (1) the role of motor impairment and particularly of those "mild parkinsonian signs" frequently detectable in elderly subjects, (2) the role of executive and attentive resources when coping with obstacles, (3) the role of vascular lesions in "highest level gait disorder" (a condition tightly connected with senile gait, cautious gait and frailty), (4) the role of the failure of automaticity or inter-limbs coordination/symmetry during walking and such approach would definitely help the development of screening instrument for subjects at risk (still lacking in present days). This translational approach will lead to the development of specific therapeutic interventions. PMID- 22673819 TI - The marriage of corneal graft and laser refractive surgery: something old and something new. PMID- 22673822 TI - Global multiplicity of dietary standards for trace elements. AB - Consistent guidelines across the world for dietary standards of trace elements remain elusive. Harmonization of dietary standards has been suggested by international agencies to facilitate consistency in food and nutrition policies and international trade. Yet significant barriers exist to standardize recommendations on a global basis, such as vast differences in geography, food availability and transport; cultural, social and economic constraints, and biological diversity. Simple commonality is precluded further by the variety of terminologies among countries and regions related to diet. Certain unions have created numerous nutritional descriptive categories for standards, while other large countries are limited to only a few. This paper will explore the global multiplicity of dietary standards and efforts for harmonization. PMID- 22673823 TI - Copper toxicity in Alzheimer's disease: cognitive loss from ingestion of inorganic copper. AB - In this review I present the hypothesis that a toxic substance, inorganic copper, ingested from drinking water and vitamin/mineral supplements containing inorganic copper, is at least partially causal of the epidemic of Alzheimer's disease (AD) we are seeing in developed countries. I set the stage for this hypothesis by pointing out that the epidemic is a new disease phenomenon coinciding temporally with the use of copper plumbing in developed countries. The evidence is good that AD was nonexistent or rare in the 1800 s and early 1900 s, and the arguments that elderly people did not exist in those times, or that AD was simply attributed to senility, are refuted. The web of evidence tying ingestion of inorganic copper as a causal factor in AD is strong, and includes AD animal model data where trace amounts of inorganic copper in the drinking water markedly worsened AD, human studies where ingestion of copper supplements, along with a high fat diet, is associated with a marked loss of cognition, human studies showing a markedly higher mortality in elderly women ingesting copper supplements, as well as other data. It is likely that a high fat diet works in conjunction with ingestion of inorganic copper to increase the risk of AD. It is clear that some factor toxic to the brain is present in the environment in developed countries, but not undeveloped countries, and is a major risk factor for AD. I believe that that toxic factor is ingestion of inorganic copper. PMID- 22673824 TI - Subclinical zinc deficiency impairs human brain function. AB - Experiments in other species showed zinc essential for brain growth and function. Six randomized controlled comparative treatment experiments in Chinese and Mexican-American low-income children, aged 6-9 years, middle-income US adolescents, middle-income US premenopausal women and middle income US men, found that subclinical zinc deficiency changes brain function. Simultaneous treatment with a broad mixture of other micronutrients and/or an adequate omnivorous diet appeared to enhance the efficacy of zinc. PMID- 22673825 TI - Trace elements in foods of children from Cameroon: a focus on zinc and phytate content. AB - In developing countries, complementary foods are based on local cereal porridges. These foods are poor in trace elements, with a high risk of inducing micronutrient deficiencies-the primary cause of mortality in children under the age of five. Inappropriate feeding of complementary foods is the major factor creating malnutrition and micronutrients deficiencies in Cameroon children, as well as in other developing countries. This study determined the zinc and phytate content of 30 complementary foods that were based on maize or Irish potatoes. The foods were blended or treated by dehusking, fermentation and germination. Zinc was measured by flame atomic absorption spectrophotometry and phytates by high pressure-liquid chromatography; then phytates/zinc molar ratios were calculated. Concentrations (mg/100g dry matter) ranged, respectively, from 0.20 to 2.58 (0.12 +/- 0.67) for zinc and from 0.00 to 6.04 (1.87 +/- 1.7) for phytates. The phytate/zinc ratio varied from 0.00 to 51.62 (11.12 +/- 11.53). It appears that germination and fermentation reduced the level of phytates: however, zinc levels in the samples did not change significantly. The traditional, local complementary foods were not only poor in zinc, but contained very high levels of phytates. These phytates have the potential to considerately reduce the acid extraction of zinc, and could impair its bioavailability. PMID- 22673826 TI - Validity of self-reported osteoporosis in mid-age and older women. AB - The validity of self-reported osteoporosis is often questioned, but validation studies are lacking. We validated self-reported prevalence and incidence of osteoporosis against self-reported and administrative data on medications. The concurrent validity was moderate to good for self-reported prevalent osteoporosis, but only poor to moderate for self-reported incident osteoporosis in mid-age and older women, respectively. Construct validity was acceptable for self-reported prevalent but not for incident osteoporosis. INTRODUCTION: The validity of self-reported osteoporosis is often questioned, but validation studies are lacking. The aim was to examine the validity of self-reported prevalence and incidence of osteoporosis against self-reported and administrative data on medications. METHODS: Data were from mid-age (56-61 years in 2007) and older (79-84 years in 2005) participants in the Australian Longitudinal Study on Women's Health. Self-reported diagnosis was compared with medication information from (1) self-report (n(mid) = 10,509 and n(old) = 7,072), and (2) pharmaceutical prescription reimbursement claims (n(mid) = 6,632 and n(old) = 4,668). Concurrent validity of self-report was examined by calculating agreement, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Construct validity was tested by examining associations of self-reported diagnosis with osteoporosis-related characteristics (fracture, weight, bodily pain, back pain, and physical functioning). RESULTS: Agreement, sensitivity and PPV of self-reported prevalent diagnosis were higher when compared with medication claims (mid-age women: kappa = 0.51, 95% confidence interval [CI] = 0.46-0.56; older women: kappa = 0.65, 95% CI = 0.63-0.68) than with self-reported medication (mid-age women: kappa = 0.41, 95% CI = 0.37-0.45; older women: kappa = 0.57, 95% CI = 0.55-0.59). Sensitivity, PPV and agreement were lower for self reported incident diagnosis (mid-age women: kappa = 0.39, 95% CI = 0.32-0.47; older women: kappa = 0.55, 95% CI = 0.51-0.61). Statistically significant associations between self-reported diagnosis and at least four of five characteristics were found for prevalent diagnosis in both age groups and for incident diagnosis in older women. CONCLUSIONS: The concurrent validity was moderate to good for self-reported prevalent osteoporosis, but only poor to moderate for self-reported incident osteoporosis in mid-age and older women, respectively. Construct validity was acceptable for self-reported prevalent but not for incident osteoporosis. PMID- 22673828 TI - Current perspectives on herb-drug interactions in the European regulatory landscape. AB - Herb-drug interactions have turned out not to be a major issue in the European regulatory landscape. For a minority of herbal preparations, herb-drug interactions are clinically relevant, e.g., between high-dose St.John's wort extracts and a number of chemical substances. The inclusion of adequate information on such interactions into the package leaflet is important for the safe use of the products. Information on potential interactions is also part of the official HMPC monographs. However, only for some herbal preparations described in these monographs, such a potential is known. Thus, in accordance with the relevant European guidance documents, potential interactions should be assessed critically for their clinical relevance, and a balanced assessment is required when regulatory documents are established or regulatory measures are implemented. PMID- 22673827 TI - Emergency strategies and trends in the management of liver trauma. AB - The liver is the most frequently injured organ during abdominal trauma. The management of hepatic trauma has undergone a paradigm shift over the past several decades, with mandatory operation giving way to nonoperative treatment. Better understanding of the mechanisms and grade of liver injury aids in the initial assessment and establishment of a management strategy. Hemodynamically unstable patients should undergo focused abdominal sonography for trauma, whereas stable patients may undergo computed tomography, the standard examination protocol. The grade of liver injury alone does not accurately predict the need for operation, and nonoperative management is rapidly becoming popular for high-grade injuries. Hemodynamic instability with positive focused abdominal sonography for trauma and peritonitis is an indicator of the need for emergent operative intervention. The damage control concept is appropriate for the treatment of major liver injuries and is associated with significant survival advantages compared with traditional prolonged surgical techniques. Although surgical intervention for hepatic trauma is not as common now as it was in the past, current trauma surgeons should be familiar with the emergency surgical skills necessary to manage complex hepatic injuries, such as packing, Pringle maneuver, selective vessel ligation, resectional debridement, and parenchymal sutures. The present review presents emergency strategies and trends in the management of liver trauma. PMID- 22673829 TI - The flavonoids casticin and artemetin are poorly extracted and are unstable in an Artemisia annua tea infusion. AB - A number of flavonoids including casticin and artemetin from Artemisia annua have shown synergism with artemisinin against Plasmodium falciparum, but it is unclear if the flavonoids are also extracted into a tea infusion of the plant. Using a tea infusion preparation protocol that was reported to be highly effective for artemisinin extraction, we measured casticin and artemetin extraction. There was only a 1.8 % recovery of casticin in the infusion while artemetin was undetectable. After 24 hr storage at room temperature, casticin yield declined by 40 %. These results show that although a tea infusion of the plant may extract artemisinin, the polymethoxylated flavonoids casticin and artemetin are poorly extracted and lost with storage at room temperature and thus, the tea infusion appears to lose synergistic value. PMID- 22673830 TI - Inhibition of prostate cancer (LNCaP) cell proliferation by volatile components from Nagami kumquats. AB - Fresh Nagami kumquats (Fortunella margarita) were subjected to hydrodistillation using a Clevenger-type apparatus to obtain volatile oil. The chemical composition of the volatile oil was analyzed by GC-MS using Rtx-5 Sil MS and DB Wax columns. A total of 25 volatile compounds were identified by mass spectra, retention index, and comparison with known standards. The major identified compounds are d limonene (41.64 %), beta-myrecene (16.54 %), linalyl propionate (9.55 %), and germacrene-D (5.93 %) from the Rtx-5 Sil MS column; d-limonene and beta-myrecene were also separated as major compounds on the DB wax column. The oil is rich in hydrocarbons (77.41 %) consisting of 60.05 % monoterpenes and 17.36 % sesquiterpenes. Interestingly, oxygenated hydrocarbons (17.6 %) were also found in kumquat volatile oil. Certain volatile compounds were also confirmed by positive chemical ionization and NMR spectra. Further, the volatile oil demonstrated good DPPH radical scavenging activity and antioxidant capacity. Kumquat volatile oil at 200 ppm concentration exhibited 55 %, 61 %, and 63.4 % inhibition of human prostate cancer (LNCaP) cell proliferation at 24, 48, and 72 h, respectively, by cell count assays. Significant increases in expression of bax/bcl2 and p53 proteins confirmed that volatile oil induces apoptosis. In addition, inhibition of inflammatory markers such as NF-kappaB and Cox-2 was observed. The cleavage of caspase-8 in the LNCaP cells treated with volatile oil demonstrated that apoptosis occurred through an extrinsic pathway. This is the first report of the identification and possible mechanisms of in vitro antiproliferative effects of kumquat volatile components on human prostate cancer (LNCaP) cells. PMID- 22673832 TI - Library-based discovery of DYRK1A/CLK1 inhibitors from natural product extracts. AB - The dual specificity tyrosine-phosphorylation-regulated kinase DYRK1A possesses diverse roles in neuronal development and adult brain physiology, and increased activity has been linked to neurodegenerative diseases. Very few inhibitors of this kinase have been reported up to now. Screening of a library of > 900 plant and fungal extracts afforded 25 extracts with IC50s < 10 ug/mL against DYRK1A. To identify the active constituents, the extracts were submitted to a process integrating physicochemical data with biological information, referred to as HPLC based activity profiling. Follow-up investigation of four extracts led to the targeted isolation of harmine (1, IC50 0.022 uM) from Peganum harmala, emodin (3, IC50 4.2 uM) from Cassia nigricans, kaempferol (4, IC50 0.91 uM) from Cuscuta chinensis, and 3,8-di-O-methylherbacetin (11, IC50 8.6 uM), 3,3',4'-tri-O methylmyricetin (12, IC50 7.1 uM) and ombuin (15, IC50 1.7 uM) from Larrea tridentata as the active constituents. Active extracts and compounds were also tested on the closely related cdc2-like kinase CLK1. Finally, the selectivity profile of compounds was evaluated by including other members of the DYRKs and CLKs families. While the flavonoids and emodin did not show significant differences in the potency of their activities, harmine (1) was most active against DYRK1A, CLK1, and CLK4, and less potent against the other kinases, with selectivity ranging from 2- to 20-fold. PMID- 22673833 TI - Emodin protects against high-fat diet-induced obesity via regulation of AMP activated protein kinase pathways in white adipose tissue. AB - Emodin is an active herbal component traditionally used in China for treating a variety of diseases. The aim of this study was to examine the effect of emodin on the reducing lipid accumulation in white adipose tissue of high-fat diet-fed rats, and on the regulation of the expression of the genes involved in lipid metabolism to elucidate the mechanisms. After being fed a high-fat diet for two weeks, rats were dosed orally with emodin (20, 40, 80 mg/kg/day) or pioglitazone (20 mg/kg/day), once daily for eight weeks. Changes in body weight, feeding pattern, serum lipids, coronary artery risk index, and atherogenic index were investigated. Subcutaneous white adipose tissues were isolated for pathology histology and Western blot analyses. Changes of triglyceride accumulation in differentiated 3 T3-L1 adipocytes were also investigated. Emodin exhibited a significant concentration-dependent decrease in the intracellular accumulation of triglyceride in 3 T3-L1 adipocytes. Emodin (80 mg/kg/day) displayed similar characteristics to pioglitazone (20 mg/kg/day) in reducing body weight gain and plasma lipid levels as well as the coronary artery risk and atherogenic indices of high-fat diet-fed rats. Emodin also caused dose related reductions in epididymal white adipose tissue sizes in high-fat diet-fed rats. Emodin and pioglitazone enhanced the phosphorylation of AMP-activated protein kinase and its primary downstream targeting enzyme, acetyl-CoA carboxylase, upregulated gene expression of carnitine palmitoyl transferase 1, and downregulated sterol regulatory element binding protein 1 and fatty acid synthase protein levels in the epididymal white adipose tissue of high-fat diet-fed rats. Our findings suggest that emodin could attenuate lipid accumulation in white adipose tissue through AMP-activated protein kinase activation. PMID- 22673834 TI - A prenylated flavanone from Dalea elegans inhibits rhodamine 6 G efflux and reverses fluconazole-resistance in Candida albicans. AB - In previous studies, 2',4'-dihydroxy-5'-(1''',1'''-dimethylallyl)-6 prenylpinocembrin, a prenylated flavonoid isolated from Dalea elegans roots, showed activity against multiresistant Staphylococcus aureus and Candida albicans, as well as an uncoupling effect on mitochondria and antioxidant activity. The aim of this study was to evaluate the inhibitory effects of 2',4' dihydroxy-5'-(1''',1'''-dimethylallyl)-6-prenylpinocembrin and fluconazole on the efflux of rhodamine 6 G in azole-resistant C. albicans 12-99 that expresses multidrug transporters Cdr1p, Cdr2p, and Mdr1p. The effect of fluconazole and 2',4'-dihydroxy-5'-(1''',1'''-dimethylallyl)-6-prenylpinocembrin on rhodamine 6 G efflux was assessed in both azole-sensitive and azole-resistant C. albicans. Between 1 and 1000 uM, 2',4'-dihydroxy-5'-(1''',1'''-dimethylallyl)-6 prenylpinocembrin inhibited rhodamine 6 G efflux only in azole-resistant C. albicans 12-99 in a concentration-dependent manner (IC50 = 119 uM); a competitive effect was observed. It also showed selectivity of action in comparison with other flavanones (6-prenylpinocembrin, isolated from aerial parts of D. elegans, pinocembrin, naringenin, and hesperetin, all at 250 uM). To check the possible implications of the inhibition of azole efflux on cell growth, antifungal assays were conducted. Minimal inhibitory concentration values were 150 uM for 2',4' dihydroxy-5'-(1''',1'''-dimethylallyl)-6-prenylpinocembrin and higher than 400 uM for fluconazole. The combination of both compounds at either inhibitory or subinhibitory concentrations was significantly more effective than each compound separately. Minimal inhibitory concentration for fluconazole decreased by more than 400 times in the presence of 100 uM 2',4'-dihydroxy-5'-(1''',1''' dimethylallyl)-6-prenylpinocembrin, reversing azole resistance and giving values similar to those of azole-sensitive C. albicans. These data are consistent with a dual action of 2',4'-dihydroxy-5'-(1''',1'''-dimethylallyl)-6-prenylpinocembrin: direct antifungal effect on azole-resistant C. albicans 12-99 and inhibition of azole transporters, which results in reversion of fluconazole resistance. PMID- 22673835 TI - Comment on: "An efficient method to calculate the aggregated isotopic distribution and exact center-masses" by Jurgen Claesen, Piotr Dittwald, Tomasz Burzykowski, Dirk Valkenborg, J. Am. Soc. Mass Spectrom. 2012, 23, 753-763. PMID- 22673836 TI - Enhanced methylarginine characterization by post-translational modification specific targeted data acquisition and electron-transfer dissociation mass spectrometry. AB - When localizing protein post-translational modifications (PTMs) using liquid chromatography (LC)-tandem mass spectrometry (MS/MS), existing implementations are limited by inefficient selection of PTM-carrying peptides for MS/MS, particularly when PTM site occupancy is sub-stoichiometric. The present contribution describes a method by which peptides carrying specific PTMs of interest-in this study, methylarginines-may be selectively targeted for MS/MS: peptide features are extracted from high mass accuracy single-stage MS data, searched against theoretical PTM-carrying peptide masses, and matching features are subjected to targeted data acquisition LC-MS/MS. Using trypsin digested Saccharomyces cerevisiae Npl3, in which evidence is presented for 18 methylarginine sites-17 of which fall within a glycine-arginine-rich (GAR) domain spanning <120 amino acids-it is shown that this approach outperforms conventional data dependent acquisition (DDA): when applied to a complex protein mixture featuring in vivo methylated Npl3, 95% more (P=0.030) methylarginine-carrying peptides are selected for MS/MS than DDA, leading to an 86% increase (P=0.044) in the number of methylated peptides producing Mascot ion scores >=20 following electron-transfer dissociation (ETD). Notably, significantly more low abundance arginine methylated peptides (maximum ion intensities <6*10(4) cps) are selected for MS/MS using this approach relative to DDA (50% more in a digest of purified in vitro methylated Npl3). It is also demonstrated that relative to collision induced dissociation (CID), ETD facilitates a 586% increase (P=0.016) in average Mascot ion scores of methylarginine-carrying peptides. The present PTM-specific targeted data acquisition approach, though described using methylarginine, is applicable to any ionizable PTM of known mass. PMID- 22673837 TI - Linkage and branch analysis of high-mannose oligosaccharides using closed-ring labeling of 8-aminopyrene-1,3,6-trisulfonate and p-aminobenzoic ethyl ester and negative ion trap mass spectrometry. AB - A strategy based on negative ion electrospray ionization tandem mass spectrometry and closed-ring labeling with both 8-aminopyrene-1,3,6-trisulfonate (APTS) and p aminobenzoic acid ethyl ester (ABEE) was developed for linkage and branch determination of high-mannose oligosaccharides. X-type cross-ring fragment ions obtained from APTS-labeled oligosaccharides by charge remote fragmentation provided information on linkages near the non-reducing terminus. In contrast, A type cross-ring fragment ions observed from ABEE-labeled oligosaccharides yielded information on linkages near the reducing terminus. This complementary information provided by APTS- and ABEE-labeled oligosaccharides was utilized to delineate the structures of the high-mannose oligosaccharides. As a demonstration of this approach, the linkages and branches of high-mannose oligosaccharides Man(5)GlcNAc(2), Man(6)GlcNAc(2), Man(8)GlcNAc(2), and Man(9)GlcNAc(2) cleaved from the ribonuclease B were assigned from MS(2) spectra of ABEE- and APTS labeled derivatives. PMID- 22673838 TI - Management of uveal melanomas: cycloxygenase-2 as a potential molecular target. PMID- 22673840 TI - Immunohistochemical analysis of two stem cell markers of alpha-smooth muscle actin and STRO-1 during wound healing of human dental pulp. AB - Recent studies have employed two markers, alpha-smooth muscle actin (alpha-SMA) and STRO-1, to detect cells with mesenchymal stem cell properties in dental pulp. The present study aimed to explore the expression profile of alpha-SMA and STRO-1 in intact dental pulp as well as during wound healing in adult dental pulp tissue. Healthy pulps were mechanically exposed and capped with the clinically used materials MTA (ProRoot White MTA) or Ca(OH)2 to induce a mineralized barrier at the exposed surface. After 7-42 days, the teeth were extracted and processed for immunohistochemical analysis using antibodies against alpha-SMA, STRO-1 and nestin (a neurogenic cytoskeletal protein expressed in odontoblasts). In normal pulp, alpha-SMA was detected in vascular smooth muscle cells and pericytes. Double immunofluorescent staining with STRO-1 and alpha-SMA showed that STRO-1 was localized in vascular smooth muscle cells, pericytes and endothelial cells, in addition to nerve fibers. During the process of dental pulp healing, numerous alpha-SMA-positive cells emerged at the wound margin at 14 days, and the initially formed mineralized barrier was lined with alpha-SMA-positive cells similar in appearance to reparative odontoblasts, some of which co-expressed nestin. STRO-1 was abundant in nerve fibers. In the advanced stage of mineralized barrier formation at 42 days, cells lining the barrier were stained with nestin, and no staining of alpha-SMA was detected in those cells. These observations indicate that alpha-SMA-positive cells temporarily appear along the wound margin during the earlier phase of mineralized barrier formation and STRO-1 is confined in vascular and neuronal elements. PMID- 22673842 TI - The elusive tripodal tris(2-pyridyl)borate ligand: a strongly coordinating tetraarylborate. AB - Tris(2-pyridyl)borates are introduced as a new robust and tunable "scorpionate" type ligand family. A facile synthesis of this hitherto unknown ligand and its complexation to Fe(II) are described; the optical and electrochemical properties of the resulting iron complex are compared to complexes derived from tris(pyrazolyl)borate, tris(2-pyridyl)aluminate, and corresponding charge-neutral ligands. PMID- 22673841 TI - Widespread expression of zinc transporter ZnT (SLC30) family members in mouse endocrine cells. AB - Zinc is abundant in most endocrine cell types, and plays a pivotal role in the synthesis and secretion of many hormones. Recent studies have demonstrated the expression of numerous zinc transporter (ZnT) family members in the pancreas, thyroid, and adrenal glands, suggesting a role for ZnTs in regulating cellular zinc homeostasis in endocrine cells. However, the cellular distribution of ZnTs in the endocrine organs has not been well established. In the present study, the mRNA expression level, cellular distribution of ZnTs as well as liable zinc ions were examined in the mouse pituitary, adrenal glands, thyroid, and pancreas. In general, ZnT1-10 mRNA was expressed to various degrees in the detected endocrine organs, with no detectable ZnT10 mRNA in the pancreas. In the anterior pituitary, both the acidophilic and basophilic cells were immunopositive to ZnT1-5, 7, 8, except for ZnT10. In the adrenal cortex, the immunoreactivity of all the tested ZnTs, including ZnT1-5, 7, 8, 10, was observed in the zona fasciculata, and some ZnTs were detected in the zona glomerulosa, zona reticularis, and the adrenal medulla. Both the follicle epithelial cells and parafollicular cells in the thyroid gland were immunostained with ZnT1-5, 7, 8, but not ZnT10. In the endocrine pancreas, the immunoreactivity of tested ZnTs was observed to various degrees except for ZnT10 in the cytoplasm of islet cells. Furthermore, autometallographic staining showed that liable zinc was observed in the endocrine cells, such as the adrenal cortical cells, thyroid follicle epithelial cells, and the pancreatic islet cells. All together, the wide distribution of liable zinc and the phenomenon that numerous ZnT family members are partially overlapped in a subset of endocrine cells suggest an important role for the ZnT family in controlling cellular zinc levels and subsequently regulating the synthesis and secretion of hormones in the endocrine system. PMID- 22673843 TI - Cyclic and polycyclic tellurium-tin and tellurium-lead compounds--synthesis, structures and thermal decomposition. AB - The miscellaneously substituted silyltellanes tBu(2)PhSiTeSiMe(3) (1) and (Me(3)Si)(3)SiTeSiMe(3) were used to synthesize the cyclic tin(II) and lead(II) tellurolates [(tBu(2)PhSiTe)(4)M(2)] (M = Sn (2), Pb (3)), [tBu(2)PhSiTePbC(SiMe(3))(3)](2) (4) and the uncommon cluster compound [{(Me(3)Si)(3)SiTe}(4)Te(2)Sn(4)] (5). PMID- 22673844 TI - What the emergency radiologist needs to know about treatment-related complications from conventional chemotherapy and newer molecular targeted agents. AB - Emergency departments (ED) are increasingly utilized by oncology patients for disease- and treatment-related issues. With the increased use of new molecular targeted therapy (MTT) and conventional chemotherapeutic regimens, oncology patients present with a range of adverse treatment effects, some of which reveal characteristic injury patterns and imaging appearances. Knowledge of these imaging findings is critically important for early detection and prompt management in oncology patients. In this article, we present a brief review of conventional chemotherapeutic and new MTT regimens as well as address adverse reactions that bring oncology patients to the ED. PMID- 22673845 TI - EPA and DHA--protein, not fat is "where it's at"? AB - Guidelines and recommendations for the dietary intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are topics of debate. Recently, EPA and DHA intakes have been demonstrated to be associated with dietary protein intakes and not dietary fat intakes that are distinct from alpha-linolenic acid. We presently confirm these observations in a secondary analysis of baseline dietary intake data for the validation of a food frequency questionnaire (n=99). DHA intakes measured by both 3 d dietary record and food frequency questionnaire and EPA intakes measured by food frequency questionnaire were positively correlated with protein intakes. EPA and DHA were not associated with fat intakes in either assessment, while ?-linolenic acid was positively correlated with fat intakes. Future recommendations regarding the intake of omega-3 polyunsaturated fatty acids, and EPA and DHA specifically, should consider these associations that provide insight on dietary sources of EPA and DHA in the food supply. PMID- 22673846 TI - Sevenfold enhancement on porphyrin dye efficiency by coordination of ruthenium polypyridine complexes. AB - Sevenfold enhancement of photoconversion efficiency was achieved by incorporation of peripheral ruthenium complexes to a porphyrin dye, generating supramolecular effects capable of playing several key roles (e.g., transferring energy to, inhibiting aggregation, and accepting the hole generated in the porphyrin center after electron injection), providing new insights for the design of better DSSC photosensitizers. PMID- 22673847 TI - Neurotrophins and nerve regeneration-associated genes are expressed in the cornea after lamellar flap surgery. AB - PURPOSE: To determine the in vivo expression of neurotrophins (NTs) and nerve regeneration-associated genes (RAGs) after surgically creating a hinged lamellar corneal flap in thy1-YFP mice. METHODS: Lamellar corneal flaps with multiple hinges were created in thy1-YFP mice. Mice were killed at weeks 2, 4, and 8. Quantitative polymerase chain reaction was performed to determine the expression of NTs and RAGs in the corneas after lamellar transection. Nerve growth factor (Ngf), brain-derived neurotrophic factor (Bdnf), glial cell-derived neurotrophic factor (Gdnf), neurotrophin 3, neurotrophin 5, small proline-rich repeat protein 1A (Sprr1a), growth-associated protein 43 (Gap43), and beta III tubulin (Tubb3) gene expressions were analyzed. Whole-mount confocal immunofluorescence and Western analyses were performed for localization and abundance of robustly expressed genes. RESULTS: Sprouts of fine YFP-positive fronds emanating from transected (injured) nerve bundles were seen in the flap area at 2 weeks onward. Bdnf and Sprr1a were robustly and significantly expressed at 2 weeks postoperatively (>2-fold increase in expression; P<0.05). Bdnf localized to thy1 YFP+ cells in operated corneas. Sprr1a localized to corneal epithelial cell membranes. At 8 weeks, none of the NTs and RAGs had increased expression. Bdnf (rho=0.73, P=0.001) and Sprr1a (rho=0.76, P=0.001) showed a significant positive correlation with beta III tubulin. CONCLUSIONS: The neurotrophin Bdnf and RAG Sprr1a are robustly and significantly expressed during corneal nerve regeneration in vivo. PMID- 22673848 TI - Fungal keratitis responsive to moxifloxacin monotherapy. AB - PURPOSE: To report 5 cases of culture-proven fungal keratitis that resolved with moxifloxacin monotherapy. METHODS: Case reports and review of medical literature. Five patients with fungal keratitis were treated with topical moxifloxacin. RESULTS: All 5 patients had resolution of their infection with topical moxifloxacin monotherapy. CONCLUSIONS: Topical fluoroquinolone agents may have significant antifungal properties. However, the vast majority of fungal keratitis patients cannot be cured with fluoroquinolone monotherapy. An initial response of keratitis to topical fluoroquinolone therapy should not lead to the assumption that the infection is bacterial because the possibility of fungal infection cannot be ruled out on that basis. PMID- 22673849 TI - Effects of multipurpose contact lens care solutions on the adhesion of Acanthamoeba to silicone hydrogel contact lenses. AB - PURPOSE: To evaluate the effect of 7 multipurpose contact lens care solutions (MPSs) on the adhesion of Acanthamoeba (AC) to 5 silicone hydrogel contact lenses (SHCLs). METHODS: Acanthamoeba castellanii (ATCC50370) trophozoites were inoculated onto disks trimmed from SHCLs, Asmofilcon A, Galyfilcon A, Senofilcon A, Lotrafilcon B, and Balafilcon A. After 4-hour incubation, the number of adherent AC trophozoites on SHCL was counted under phase contrast microscopy. AC trophozoites mixed with 7 MPSs were inoculated onto Balafilcon A and incubated for 24 hours followed by direct counting, phase contrast microscopy, and scanning electron microscopy. AC cysts were also inoculated onto Balafilcon A followed by counting using phase contrast microscopy. RESULTS: Adhesion of AC trophozoites to Lotrafilcon B and Balafilcon A was 10 times higher in comparison with the other 3 SHCLs. Twenty four-hour treatment of AC trophozoites with Epica Cold, Epica Cold Aquamore, ReNu MultiPlus, OptiFree Plus, and Complete DoubleMoist reduced the numbers of adherent AC to less than 25% of control, whereas the numbers of AC treated with Complete AminoMoist and C3 SoftOne Moist was about 50% and 75% of control, respectively. Normal AC trophozoites without any treatments showed 25 times higher adhesion rates compared with normal AC cysts. CONCLUSIONS: The adhesion rates of AC trophozoites to SHCL varied depending on the type of MPSs used. Appropriate uses of MPS could reduce adhesion rates of AC to SHCL and potentially decrease clinical rates of Acanthamoeba keratitis. PMID- 22673850 TI - Prevalence of undiagnosed HIV infection in patients with ocular surface squamous neoplasia in a tertiary center in Karnataka, South India. AB - PURPOSE: To evaluate the prevalence of undiagnosed and asymptomatic human immunodeficiency virus (HIV) infection in patients with ocular surface squamous neoplasia (OSSN) in a referral hospital in Karnataka, South India. METHODS: A consecutive series of patients presenting with OSSN were evaluated in an academic center during January 2009 to June 2010. A detailed history was obtained and physical examination in 25 consecutive patients with OSSN was performed. Twenty three patients (88%) agreed to undergo serological HIV testing. Of these, 2 were excluded from the current study because they had xeroderma pigmentosa, a known predisposing factor for OSSN. RESULTS: Of the 21 patients, 6 (29%) patients were HIV positive. None of the patients had previous HIV testing. The median age of presentation among HIV-positive patients was 36 years, whereas it was 54 years among HIV-negative patients. The mean CD4 count in HIV-positive patients was 133 cells per mm, and all patients were started on antiretroviral treatment. CONCLUSIONS: The conjunctival tumor may be the primary and the only apparent manifestation of HIV in patients presenting with OSSN, and the ophthalmologist needs to be aware of this association. PMID- 22673851 TI - The effect of riboflavin-UV-A treatment on corneal limbal epithelial cells--a study on human cadaver eyes. AB - PURPOSE: To determine the effect of riboflavin-UV-A treatment on the corneal limbal epithelial cells during a corneal collagen cross-linking (CXL) procedure. METHODS: Thirty freshly enucleated human cadaveric eyeballs were subjected to a CXL procedure, mimicking the clinical protocol. During the UV-A exposure, one half of the limbus (sector A) was left unprotected, whereas the other half (sector B) was covered by a metal shield. Limbal biopsies from both sectors before and after the procedure were analyzed. Each strip of tissue was divided into 3 segments, for cell count of viable cells, for cultivation on human amniotic membrane (HAM), and for stem cell and differentiated corneal epithelial cell marker studies using reverse transcriptase-polymerase chain reaction. RESULTS: Compared with the cell count before CXL, there was a statistically significant drop in the mean number of viable cells after CXL in sector A but not in sector B. Biopsies from both sectors before CXL and from sector B after CXL showed good growth on HAM. Biopsies from sector A after CXL showed no growth on HAM. The putative stem cell marker ABCG2 was absent in all samples and p63 was absent in 3 of 10 samples taken from sector A after CXL. All markers were present in all samples from sector B after CXL. CONCLUSIONS: Riboflavin-UV-A treatment can result in damage to limbal epithelial cells, particularly the stem cells. Covering the limbal region with a metal shield effectively prevents this damage. PMID- 22673852 TI - The practical detection of mmp-9 diagnoses ocular surface disease and may help prevent its complications. AB - PURPOSE: To evaluate the importance and practicality of testing for matrix metalloproteinase 9 (MMP-9) in dry eye and ocular surface disease. This enzyme, which can cause tissue damage, seems also to be the most reliable diagnostic indicator of ocular surface disease. METHODS: Enzyme-linked immunosorbent assay, polymerase chain reaction, diffusion, and InflammaDry, a new rapid immunoassay by RPS (Rapid Pathogen Screening Inc). RESULTS: MMP-9 measurement is sensitive and accurate for diagnosing dry eye and ocular surface disease and compares favorably in both sensitivity and specificity against the existing methods of dry eye diagnosis. Abnormal elevations of MMP-9 may predict post-laser in situ keratomileusis complications and refractive complications such as epithelial ingrowth and corneal ulceration. The presence of elevated MMP-9 on the ocular surface will identify those patients who should receive antiinflammatory therapy, such as cyclosporine, and may predict those patients who will respond to this therapy. CONCLUSIONS: A rapid in-office test that is sensitive for identifying inflammatory dry eye and ocular surface disease may facilitate better preoperative management of the ocular surface. Optimization of the ocular surface perioperatively would be expected to reduce complications from laser in situ keratomileusis and other surgeries that often make the underlying disease worse. This test may also indicate the need for antiinflammatory therapies, such as cyclosporine or steroids, and also may predict those patients who are more likely to respond. PMID- 22673853 TI - Corneal inflammation from pine processionary caterpillar hairs. AB - PURPOSE: Hairs from the caterpillar of the pine processionary moth, Thaumetopoea pityocampa, located in the pine forests of southern Europe and elsewhere, can become embedded in the cornea and conjunctiva. Disorders produced by the urticating hairs can be classified into a broad spectrum of severity from mild keratoconjunctivitis to anaphylactic shock. This report presents 3 cases that illustrate the range of corneal responses to embedded hairs of the processionary moth caterpillar. METHODS: Case series and review of the literature. RESULTS: A 51-year-old man (case 1), a 46-year-old woman (case 2), and a 67-year-old man (case 3) presented different manifestations as a result of contact with pine processionary caterpillar hairs. Case 1 had acute keratitis with decreased vision. He was treated with a corneal depot steroid 4 times daily for 3 months. After 4 months, he was asymptomatic. Case 2 had acute keratitis without vision symptoms. She was released without treatment, and 1 month later was asymptomatic. Case 3 experienced dry gritty sensations, probably because of blepharitis, but also presented asymptomatic caterpillar hairs embedded in the corneal stroma. He was instructed regarding lid hygiene for his blepharitis, and after 3 months the embedded caterpillar hairs had disappeared. CONCLUSIONS: The most common ocular presentation of embedded hairs from the pine processionary moth caterpillar is keratitis. The urticating hairs can cause corneal infiltrates that disappear progressively over time. Steroid eye drops accelerate the resorption of these infiltrates. PMID- 22673854 TI - Rebound, applanation, and dynamic contour tonometry in pathologic corneas. AB - PURPOSE: To compare the practicability of using an Icare rebound tonometer (RT) versus a Goldmann applanation tonometer (GAT) or a Pascal dynamic contour tonometer (DCT) for measuring intraocular pressure (IOP) in patients with corneal abnormalities and, furthermore, to study the influence of central corneal thickness, corneal diameter, corneal radius, and axial length. METHODS: One hundred seventy-one pathologic eyes with corneal abnormalities and 26 nonpathologic control eyes of 99 patients were included. Pathologic corneas were divided into subgroups: previous keratoplasty, keratoconus, corneal scars, corneal dystrophies, and bullous keratopathy. RESULTS: Although IOP was successfully measured using the RT in all pathologic eyes, successful measurement of IOP was only possible in 98.2% when using the GAT and in 73.1% with the DCT. Mean IOP for all enrolled eyes was 12.7 +/- 4.1 mm Hg for RT, 15.5 +/- 4.4 mm Hg for GAT, and 16.3 +/- 4.1 mm Hg for DCT. The mean difference between RT and GAT was <= 1 mm Hg (<= 2 mm Hg) [<= 3 mm Hg] in 23.4% (41.8%) [62.0%] of cases. Correlation analysis showed a moderate correlation between RT and GAT (r = 0.566; P < 0.001) and between RT and DCT (r = 0.364; P < 0.001). Bland-Altman analysis revealed a bias between RT and GAT and between RT and DCT of -2.8 and -3.8 mm Hg, with limits of agreement of -10.5 to 4.9 mm Hg and -12.2 to 4.6 mm Hg, respectively. CONCLUSION: In pathologic corneas, IOP was difficult to obtain with GAT and DCT, whereas RT was able to determine IOP in all pathologic corneas. RT significantly underestimated IOP in all groups in relation to GAT and DCT. The agreement between the methods was clinically acceptable in corneal dystrophy and keratoconus but poor in eyes after keratoplasty. PMID- 22673855 TI - Argon laser phototherapy in the treatment of refractory fungal keratitis. AB - PURPOSE: To report the beneficial properties of argon laser as an adjunctive therapy in 2 patients with refractory fungal keratitis. METHODS: Case reports and a review of the literature. Two cases of Fusarium keratitis refractory to topical and systemic antifungals were further treated with argon laser. Before laser treatment, the eye was medicated with proparacaine 0.5%, lidocaine 4%, and a single drop of fluorescein sodium 0.25%. Argon laser irradiation of the affected cornea was performed using argon blue-green wavelength (Coherent Ultima 2000; Coherent, Inc). A spot size of 500 MUm, pulse duration of 0.10 seconds, and power ranging from 500 to 900 mW were used. RESULTS: During the first week after laser treatment, both patients showed complete resolution of the infiltrates. Two signs were observed during the procedure: a blanching of the corneal stroma and small cavitations that reached the middle stroma. No adverse effects were observed. CONCLUSIONS: Argon laser phototherapy is useful as an adjunctive treatment of refractory fungal keratitis. More cases are needed to validate our findings. PMID- 22673856 TI - Object-based attention: a tutorial review. AB - This tutorial provides a selective review of research on object-based deployment of attention. It focuses primarily on behavioral studies with human observers. The tutorial is divided into five sections. It starts with an introduction to object-based attention and a description of the three commonly used experimental paradigms in object-based attention research. These are followed by a review of a variety of manifestations of object effects and the factors that influence object segmentation. The final two sections are devoted to two key issues in object based research: the mechanisms that give rise to the object effects and the role of space in object-based selection. PMID- 22673857 TI - Dissociating location-specific inhibition and attention shifts: evidence against the disengagement account of contingent capture. AB - The study of attentional capture has provided a rich context for assessing the relative influence of top-down and bottom-up factors in visual perception. Some have argued that attentional capture by a salient, irrelevant stimulus is contingent on top-down attentional set (e.g., Folk, Remington, & Johnston, Journal of Experimental Psychology: Human Perception and Performance 18:1030 1044, 1992). Others, however, have argued that capture is driven entirely by bottom-up salience and that top-down factors influence the postallocation speed of disengagement from the irrelevant stimulus (e.g., Theeuwes, Acta Psychologica 135:77-99, 2010a). In support of this speed-of-disengagement hypothesis, recent findings from the modified spatial-cuing paradigm show that cues carrying a no-go target property produce reverse, or negative, cuing effects, consistent with inhibition of the cue location from which attention has been very quickly disengaged (Belopolsky, Schreij, & Theeuwes, Perception, & Psychophysics, 72, 326 341, 2010). Across six experiments, we show that this inhibitory process can be dissociated from shifts of spatial attention and is, thus, not a reliable marker of capture. We conclude that the data are inconsistent with the predictions of the disengagement hypothesis. PMID- 22673858 TI - Age of first words predicts cognitive ability and adaptive skills in children with ASD. AB - Acquiring useful language by age 5 has been identified as a strong predictor of positive outcomes in individuals with Autism Spectrum Disorders (ASD). This study examined the relationship between age of language acquisition and later functioning in children with ASD (n = 119). First word acquisition at a range of ages was probed for its relationship to cognitive ability and adaptive behaviors at 52 months. Results indicated that although producing first words predicted better outcome at every age examined, producing first words by 24 months was a particularly strong predictor of better outcomes. This finding suggests that the historic criterion for positive prognosis (i.e., "useful language by age 5") can be updated to a more specific criterion with an earlier developmental time point. PMID- 22673859 TI - Who participates in support groups for parents of children with autism spectrum disorders? The role of beliefs and coping style. AB - One hundred forty-nine parents of children with autism spectrum disorders (ASD) completed online questionnaires measuring their beliefs about support groups and ASD, coping style, social support, mood, and use of support groups. Those currently using parent support groups (PSGs) reported using more adaptive coping strategies than both parents who had never used PSGs and parents who had used PSGs in the past. Past PSG users reported that they did not find the groups as beneficial as current users, and parents who had never participated in PSGs reported difficulties with the accessibility of PSGs. Based on the current results, interventions for parents of children with ASD that are focused on meeting the needs identified by participating parents may be most effective. PMID- 22673860 TI - Autism severity and qualities of parent-child relations. AB - The aim of this study was to examine how severity of autism affects children's interactions (relatedness) and relationships with their parents. Participants were 25 parent-child dyads that included offspring who were children with autism aged from 4 to 14 years. The severity of the children's autism was assessed using the calibrated severity metric of the Autism Diagnostic Observation Schedule (Gotham et al. in J Autism Dev Disord 39:693-705, 2009). Parent-child dyads were videotaped in 10-min semi-structured play interactions, and qualities of interpersonal relatedness were rated with the Dyadic Coding Scales (Humber and Moss in Am J Orthopsychiatr 75(1):128-141, 2005). Quality of relationships between parents and children were evaluated with a parent self-report measure, the Parent Child Relationship Inventory (Gerard in Parent-Child Relationship Inventory (PCRI) manual. WPS, Los Angeles, 1994). Multivariate regression analysis revealed that severity of autism was inversely related to patterns of parent-child interaction but not to reported quality of parent-child relationship. We consider the implications for thinking about relatedness and relationships among children with autism, and opportunities for intervention. PMID- 22673861 TI - The effect of different gloss levels on in-line monitoring of the thickness of printed layers by NIR spectroscopy. AB - Near-infrared (NIR) reflection spectroscopy was used for monitoring the thickness or rather the coating weight of thin printed layers of transparent oil-based offset printing varnishes in a range from 0.5 to 5 g m(-2). Quantitative analysis of the spectral data was carried out with partial least squares regression. Surface properties such as the gloss were found to strongly affect the prediction of the coating weight. This influence was minimized by the development of calibration models, which contained spectra of layers with a broad range of gloss levels. The prediction error of these models was in the order of 0.12 to 0.16 g m(-2). In-line measurements were carried out at a sheet-fed offset printing press in order to test the performance of the models under real process control conditions. Varnishes were applied to paper at printing speeds of 90 or 180 m min(-1). A close correlation between the predictions from in-line NIR spectra and the reference data from gravimetry was observed regardless of the specific degree of gloss of the layers (errors between 0.15 and 0.17 g m(-2)). The results clearly prove the efficiency of NIR reflection spectroscopy for quantitative investigations on thin layers in fast processes such as printing and demonstrate its analytical potential for quality and process control. PMID- 22673862 TI - Hinge sequences as signaling agents? AB - We report an unexpected finding of common structural principles in two unrelated signaling systems: the FAS death domain transformation that initializes the extrinsic apoptotic pathway and signaling by calmodulin bending. The location and design of the hinge is postulated to be a general principle for creating potential signaling event. We suggest that already existing tool can predict the existence of such a hinge and formulate the hypothesis that the internal instabilities designed into the hinge sequences are necessary devices in effective signaling events. PMID- 22673863 TI - Periprocedural myocardial enzyme elevation: prognostic implications for current practice. AB - With the high volume of yearly cardiovascular revascularization procedures, periprocedural myocardial enzyme elevation remains an important topic. Although periprocedural myocardial enzyme elevation has been used in the universal definition of myocardial infarction, most hospitals do not routinely measure postprocedural cardiac enzymes. Multiple studies have illustrated the prognostic implications of such biomarker elevations on mortality and cardiovascular outcomes (especially in the short term), yet the question of routine marker assessments remains vexing. Heterogeneity in these studies has caused debate to continue regarding the appropriate cutoff levels, choice of biomarker assay, and situations in which markers should be measured. Along with the clinical implications of clarifying these issues, we acknowledge the impact on the management and interpretation of our large-scale, practice-altering clinical trials. In this review, we highlight significant concepts in the diagnosis, prognosis, and clinical impact of periprocedural myocardial enzyme elevation. PMID- 22673864 TI - Body weight changes in child and adolescent athletes during a triathlon competition. AB - We examined young athletes during a triathlon performed in a hot climate. Complete or partial data were available for 95 athletes competing in the National Triathlon Championship in Costa Rica. Mean +/- SD for age and body weight (BW) were 13.1 +/- 2.5 years and 46.3 +/- 11.5 kg, respectively. Race requirements included: 500 m swimming, 15 km cycling, 3.5 km running for juniors (9-13 years); 800 m swimming, 30 km cycling, 8 km running for seniors (14-17 years). WBGT on race day was >31 degrees C. BW recorded pre- and post-race was available for 92 athletes and performance data were available for 83 of these. Information regarding symptoms experienced during the race was available for 95 athletes. Change in BW (%DeltaBW) was calculated and ranged from +0.6 to -2.4 % for junior boys (-1.2 +/- 0.9 %), +0.7 to -2.5 % for junior girls (-1.3 +/- 0.9 %), 0 to 2.8 % for senior girls (-1.3 +/- 0.9 %), and +0.6 to -4.5 % for senior boys (-1.7 +/- 1.1 %). Eighteen participants reported no medical symptoms. Of 77 participants who reported symptoms, 42.9 % reported exhaustion/fatigue, 36.4 % reported side stitch/cramp, and 23.4 % reported dizziness. Participants reporting no medical symptoms achieved almost identical (P = 0.99) %DeltaBW as those reporting at least one symptom. %DeltaBW was more negative (P = 0.005) in participants who reported dizziness (-1.9 %DeltaBW) compared with those who did not (-1.4 %DeltaBW). %DeltaBW was associated with performance in junior girls (r = 0.47, P = 0.02) and senior boys (r = 0.51, P = 0.01), with a trend in junior boys (r = 0.41, P = 0.053) but not in senior girls (r = 0.004, P = 0.99). Young athletes participating in a triathlon in a hot climate can tolerate mild to moderate levels of dehydration, without detrimental effects to self-assessed health. PMID- 22673865 TI - [Do we always measure the same? On measurement invariance and response shift in rehabilitation research - part 2]. AB - Interventions in medical rehabilitation are often evaluated using a single-group pre-post study design with health-related quality of life (hrqol) as an outcome variable. Through comparison of mean values in hrqol subscales treatment effects are calculated. In many cases conclusions about changes in hrqol are made depending on the sizes of effects. The precondition for doing this, however, is that the answers to the items in questionnaires were given within the same frames of internal standards, values and conceptualizations at the different time points. Changes in these frames can be found, however, and are discussed under the term response shift, which can happen when adjusting to chronic and progressive diseases. Existence of response shift can be proven with confirmatory factor analysis (CFA) by measuring hrqol at different time points. This approach can be assigned to the broader issue of measurement of invariance in longitudinal studies and is described in a sample of 279 patients with diabetes mellitus. Different response shift processes were detectable. If response shift takes place but is not taken into account inferences from changes in scale scores to changes in hrqol are invalid. This means that the calculation of effect size is also influenced by response shift. By the use of CFA conventionally calculated effect size can be differentiated into either effects due to response shift or 'true change' of hrqol. Measurements of invariance within one group at 2 time points can be differentiated from multiple group analysis at one time point. Investigations of measurement of invariance in longitudinal studies allow for conclusions regarding sensitivity to change of instruments examining hrqol changes. This is important for clinicians who make decisions about which scales are appropriate to detect hrqol changes. For scientific research it is relevant for further analysis of sensitivity to change of hrqol instruments. PMID- 22673866 TI - [A meta-analysis of the impact of sample, kind of outcome measurement and time of follow up on occupational re-integration after vocational retraining]. AB - OBJECTIVES: Vocational Rehabilitation (VR) is an essential element of intervention to rehabilitate people with work disability due to chronic diseases. The activities are heterogeneous; of particular importance in the rehabilitation process is vocational retraining. These interventions are cost-intensive, take very long and have a decisive impact on the main goal, the return to work (RTW). However, vocational retraining is conducted under different settings: The question is to what extent this leads to specific methodical implications of RTW measurement that have an impact on the level of RTW. METHODS: The analysis was concentrated on the main outcome RTW after vocational retraining. A structured review was conducted of all German-language publications from 2005 to 2010 which report an RTW quota after vocational retraining. The main methodical conditions were: kind of RTW measurement (point in time rate vs. cumulative course rate), time of follow-up in years, and sample definition (all participants vs. participants with regular completion of retraining, RC). The impact of these conditions on the level of RTW was predicted by using a meta-regression model. The time of follow-up was standardized on the mean (1 year). RESULTS: 20 publications from 10 studies were included in the analysis. In all, 23 RTW quota were observed, from which 22 were included in the regression model. A positive impact on the level of RTW was identified for reduction of the sample to participants with RC (b=10.04; p=0.001), the time of follow-up (b=5.47; p=0.052) and, by trend, the interaction of the kind of RTW measurement and time of follow up (b=6.32; p=0.090). There was no significance given for the main effect of kind of RTW measurement (p=0.787). The model fit was calculated with an adjusted R2=75.17%. CONCLUSIONS: The level of RTW given in the publications is very heterogeneous, but a major part of the variance was explained by the 3 methodical conditions we examined. Based on this, a classification system for RTW measurement after VR is presented, which could be a model for designing future studies as well as inter-actor communication of success after VR. PMID- 22673867 TI - [Rehabilitation results of Turkish immigrants - an analysis of routine data from the Rhineland and Westfalia Pension Insurance]. AB - AIMS OF THE STUDY: Approximately 3 million Turkish immigrants are living in Germany, in North Rhine-Westfalia their share amounts to 4.7%. They use the same rehabilitation services as Germans, but their treatment usually shows less positive results - as other studies have shown. The aims of the research project "Immigration and Health Inequalities in Rehabilitation" were (a) to quantify the use of medical rehabilitation by Turkish immigrants in different diagnosis groups, (b) to compare outcomes in different diagnosis groups and (c) to find out whether the results will be explained by immigrant status, or by socio-economic factors accompanying immigrant status. METHODS AND RESULTS: An analysis of routine data from Deutsche Rentenversicherung Rheinland and Deutsche Rentenversicherung Westfalen (Rhineland and Westfalia Pension Insurances) was carried out, pertaining to 363 855 persons who had participated in at least one rehabilitation procedure between 2000 and 2006. 4.8% of all rehabilitees were identified as being of Turkish origin. A modified name-based algorithm was used to help to identify Turkish rehabilitees. The outcome of rehabilitation was measured by comparing the medical discharge assessments. Turkish people were in need of rehabilitation more often because of mental disorders/behavioural disturbances (Turkish men=22.0% vs. non-Turkish men=18.4% [p<0.001]; Turkish women=30.8% vs. non-Turkish women=21.6% [p<0.001]) and less often because of neoplasms (Turkish men=4.7% vs. non-Turkish men =7.8% [p<0.001]; Turkish women=6.4% vs. non-Turkish women=13.9% [p<0.001]). Concerning treatment results in several diagnosis groups Turkish rehabilitees benefitted less from treatment than non-Turkish rehabilitees did (musculoskeletal disorders: OR=2.08 [95% CI=1.97-2.20]; mental disorders/behavioural disturbances: OR=1.70 [95%-CI=1.57 1.84]; respiratory diseases: OR=1.41 [95%-CI=1.14-1.75]; digestive disorders/metabolic diseases: OR=1.36 [95%-CI=1.11-1.66]). Non-Turkish rehabilitees had higher chances of success, even adjusted by social and performance-related factors. The differences were non-significant only in cardio vascular disease and neoplasm treatment. CONCLUSIONS: Rehabilitation outcomes are significantly less favourable for Turkish people. The differences found can partially be traced to factors related to their migration background and not only to other social differences or performance-related factors of the health services. Immigrant status, hence, affects rehabilitation outcome and must receive attention in both rehabilitation plans and rehabilitation facilities. PMID- 22673868 TI - [Intention to use and use of treatment due to psychological distress of patients in somatic rehabilitation]. AB - BACKGROUND AND OBJECTIVES: Somatically ill patients in somatic rehabilitation often show comorbid psychological distress and mental disorders. In the framework of the implementation of a stepwise psychodiagnostic procedure, the present study investigated the intention to use and the use of treatment due to psychological distress. METHODOLOGY: Cohort study with a 6-months follow-up in 5 orthopedic, cardiologic and oncologic inpatient rehabilitation clinics (n=1 374). Psychological distress, sociodemographic data, intention to use psychotherapeutic or psychiatric treatments and the use of health care offers due to psychological distress were assessed by means of questionnaires. RESULTS: Every third patient (34%) was psychologically distressed at the beginning of rehabilitation. A positive intention to use psychotherapeutic or psychiatric treatment was reported by 79% of the psychologically distressed patients. 6 months after the end of rehabilitation, 26% of the patients who were psychologically distressed at the beginning of rehabilitation, had received treatment for mental health reasons. Reasons for non-utilization of treatment included lack of subjective need (45%) and lack of interest in treatment despite a perceived need (30%). Further 25% were considering treatment or were seeking appropriate treatment. CONCLUSIONS: Psychologically distressed rehabilitation patients show a high intention to undergo treatment. However, they show a clearly diminished use of post rehabilitative treatments due to mental health problems. Hence, the promotion of motivation as well as the management of treatment barriers for improving post rehabilitative use in psychologically distressed rehabilitants are of particular importance. PMID- 22673869 TI - [Psychological interventions in the rehabilitation of patients with coronary heart disease: summary of evidence and recommendations from systematic reviews and guidelines]. AB - OBJECTIVE: To summarize national and international evidence and recommendations for psychological interventions in the rehabilitation of patients with coronary heart disease. Background is a project for the development of evidence-based practice guidelines for psychological interventions in the rehabilitation of patients with coronary heart disease. METHODS: A systematic literature search in several databases and on the websites of professional associations was conducted in order to identify relevant reviews and guidelines. A handsearch was conducted in addition to the electronic search. Eligible publications were selected, and evidence for psychological interventions was extracted as well as recommendations relative to psychological diagnostics or interventions. RESULTS: 5 systematic reviews and 34 guidelines were included. Recommendations and (partially restricted) evidence from systematic reviews was found for the following psychological interventions: patient counselling and health education; screening and treatment of comorbid psychological disorders; occupational counselling; stress management; relaxation training; interventions for smoking cessation; interventions promoting appropriate nutrition and weight management; interventions enhancing sufficient, regular physical activity; interventions enhancing social support; specific interventions for women; involvement of family members or partners; discussion of sexual activity. DISCUSSION/CONCLUSION: For several psychological interventions in the treatment of patients with coronary heart disease we found empirical evidence from systematic reviews. For other psychological interventions, no empirical evidence from systematic reviews was found. The summary of guidelines shows that both in Germany and abroad, a number of psychologically grounded interventions are an inherent part of cardiac rehabilitation. However, many recommendations which refer to psychological diagnostics and interventions are not precise enough to guide psychological care of individual patients. In particular, there are no statements in many guidelines on which (psychological) treatments should be considered for which problems. Moreover, hardly any evidence or recommendations were found for specific interventions referring to special groups of patients (e.g., women, patients with low socio-economic status or migration background). Further research is needed in these respects in order to answer questions concerning the indication and effectiveness of such tailored interventions. PMID- 22673870 TI - [Effects of inpatient preventive and rehabilitative measures for mothers and their children - a controlled comparison trial]. AB - PURPOSE: Rehabilitation measures have for a long time been evaluated primarily by means of pre-post comparisons of the group examined or by comparing different intervention programmes. This study was aimed at examining the current status and medium-term changes of mothers' health and psychosocial situation, comparing mothers with or without approval and participation in an inpatient mother-child rehabilitation measure. METHOD: The sample consisted of 477 women. The first survey (T1) took place at the time of application; the postal follow-up survey (T2) was carried out 6 months later. At this point 353 mothers had completed their measure (IG=intervention group); 75 women had not yet started (WG=waiting group), and 49 applications had finally been rejected (AG=rejected group). This study examines how far the 3 groups differ with respect to their health parameters at the time of application as well as 6 months later. The outcome variables, containing health complaints, somatic and mental illnesses, psychosocial factors (e. g., single parenthood), or restrictions of daily activities and the range of participation in family and job affairs, were selected following the assessment guidelines of the Medical Review Board of the Statutory Health Insurance Funds (MDS). Duration and severity of symptoms were measured with Likert scales (indirect measurement of change), the mental health status with SCL-K-9. RESULTS: At the time of application the 3 groups of mothers did not differ significantly with respect to their complaints and symptoms, but some minor tendencies became apparent. Mothers, who were admitted for the intervention (IG and WG) showed more complaints and symptoms than mothers, whose applications had been rejected (AG). 6 months later, highly significant changes and clinically important improvements were observed for IG mothers: large effects were achieved regarding the number of illnesses, health complaints, the degree of daily activities and participation as well as mental health of participants. Minor effects were obtained with respect to psychosocial strains. In contrast the number of illnesses and health complaints among mothers, who had not (yet) participated, increased within half a year. Similarly, psychological strains were greater than before: in the waiting group they had risen significantly, in the rejected group values resembled those of the intervention group before intervention. CONCLUSION: Inpatient measures do not only cause short-term improvements of mothers' health status, they also lead to clinically relevant reductions of health impairments and complaints in the medium term. In contrast, the health status of mothers, who miss the intervention, deteriorates. This also applies to mothers, who were rejected. Therefore, it is highly recommended to take the self-reporting forms into account when identifying mothers for the intervention, and also to start the intervention early after the approval. PMID- 22673871 TI - An organocatalytic direct Mannich-cyclization cascade as [3+2] annulation: asymmetric synthesis of 2,3-substituted pyrrolidines. AB - A new method for asymmetric synthesis of 2,3-substituted pyrrolidines from N-PMP aldimines and succinaldehyde via formal [3+2] cycloaddition is reported. This reaction involves proline catalyzed direct Mannich reaction and acid catalyzed reductive cyclization with high yields (up to 78%) and excellent enantioselectivities (up to >99%). PMID- 22673872 TI - Effects of ADARs on small RNA processing pathways in C. elegans. AB - Adenosine deaminases that act on RNA (ADARs) are RNA editing enzymes that convert adenosine to inosine in double-stranded RNA (dsRNA). To evaluate effects of ADARs on small RNAs that derive from dsRNA precursors, we performed deep-sequencing, comparing small RNAs from wild-type and ADAR mutant Caenorhabditis elegans. While editing in small RNAs was rare, at least 40% of microRNAs had altered levels in at least one ADAR mutant strain, and miRNAs with significantly altered levels had mRNA targets with correspondingly affected levels. About 40% of siRNAs derived from endogenous genes (endo-siRNAs) also had altered levels in at least one mutant strain, including 63% of Dicer-dependent endo-siRNAs. The 26G class of endo-siRNAs was significantly affected by ADARs, and many altered 26G loci had intronic reads and histone modifications associated with transcriptional silencing. Our data indicate that ADARs, through both direct and indirect mechanisms, are important for maintaining wild-type levels of many small RNAs in C. elegans. PMID- 22673873 TI - Effective combination of hydrostatic pressure and aligned nanofibrous scaffolds on human bladder smooth muscle cells: implication for bladder tissue engineering. AB - Bladder tissue engineering has been the focus of many studies due to its highly therapeutic potential. In this regard many aspects such as biochemical and biomechanical factors need to be studied extensively. Mechanical stimulations such as hydrostatic pressure and topology of the matrices are critical features which affect the normal functions of cells involved in bladder regeneration. In this study, hydrostatic pressure (10 cm H(2)O) and stretch forces were exerted on human bladder smooth muscle cells (hBSMCs) seeded on aligned nanofibrous polycaprolactone/PLLA scaffolds, and the alterations in gene and protein expressions were studied. The gene transcription patterns for collagen type I, III, IV, elastin, alpha-SMA, calponin and caldesmon were monitored on days 3 and 5 quantitatively. Changes in the expressions of alpha-SMA, desmin, collagen type I and III were quantified by Enzyme-linked immuno-sorbent assay. The scaffolds were characterized using scanning electron microscope, contact angle measurement and tensile testing. The positive effect of mechanical forces on the functional improvement of the engineered tissue was supported by translational down regulation of alpha-SMA and VWF, up-regulation of desmin and improvement of collagen type III:I ratio. Altogether, our study reveals that proper hydrostatic pressure in combination with appropriate surface stimulation on hBSMCs causes a tissue-specific phenotype that needs to be considered in bladder tissue engineering. PMID- 22673875 TI - Neural correlates of after-effects caused by adaptation to multiple face displays. AB - Adaptation to a given face leads to face-related, specific after-effects. Recently, this topic has attracted a lot of attention because it clearly shows that adaptation occurs even at the higher stages of visual cortical processing. However, during our every-day life, faces do not appear in isolation, rather they are usually surrounded by other stimuli. Here, we used psychophysical and fMRI adaptation methods to test whether humans adapt to the gender properties of a composite multiple face stimulus as well. As adaptors we used stimuli composed of eight different individual faces, positioned peripherally in a ring around a fixation mark. We found that the gender discrimination of a subsequent centrally presented target face is significantly biased as a result of long-term adaptation to either male or female multiple face stimuli. Similar to our previous results with single-face adaptors (Kovacs et al. in Neuroimage 43(1):156-164, 2008), a concurrent functional magnetic resonance imaging adaptation experiment revealed the strongest blood oxygen level-dependent signal adaptation bilaterally in the fusiform face area. Our results suggest that humans extract the statistical features of the multiple face stimulus and this process occurs at the level of occipito-temporal face processing. PMID- 22673877 TI - The induction of Treg cells by gut-indigenous Clostridium. AB - Foxp3+ CD4+ cells are prominent immune regulatory T (Treg) cells that are most abundant in the intestine. Recent studies have suggested that intestinal Treg cells consist of thymically and extrathymically developed cells that have unique characteristics. A fraction of intestinal Treg cells express T cell receptors that recognize antigens that are derived from the gut microbiota. The presence of the gut microbiota, particularly the Clostridium species, affects the development and function of Treg cells. These intestinal bacteria-induced Treg cells are likely to play a role in the tolerance toward the gut microbiota. These recent advances provide new insight into how T cells are educated in the intestine to maintain homeostasis with the gut microbiota. PMID- 22673876 TI - Unique features of antiviral immune system of the vaginal mucosa. AB - A vast majority of human vaccines rely on neutralizing antibodies for protection. With the exception of vaccines against human papillomavirus, despite a great amount of dedicated effort by the scientific community, development of vaccines against sexually transmitted viruses has generally been unsuccessful. Understanding the immunobiology of the genital tract is key to designing vaccines that prevent spreading of these viruses. Recent studies demonstrate that adaptive immunity in the vaginal mucosa is uniquely regulated compared to other mucosal organs. In particular, development of virus-specific CD4+ and CD8+ T cells is critically important for antiviral defense in vagina. In this review, we provide an overview of our current understanding of a wide spectrum of immune responses in vagina--from innate viral sensing to memory development. PMID- 22673878 TI - Coping with uncertainty on health decisions: assessing new solutions. PMID- 22673880 TI - The contributions of language and experience to the representation of abstract and concrete words: different weights but similar organizations. AB - In the present studies, we evaluated the contributions of language and sensorimotor information to the representation of abstract and concrete words and the possibility that the organizations of the two types of concepts follow different organizational principles: association, for abstract concepts, and semantic similarity, for concrete concepts. In Study 1, we examined the two strongest associates of concrete and abstract words from published free association norms. Study 2 then extended this analysis to individual data collected with a free association task. Language associations were more important for abstract than for concrete words, but for sensorimotor information no differences were observed between the two types of concepts. Also, no clear evidence was found for different qualitative organizational principles for abstract and concrete concepts. Multiple representational systems thus seem to be engaged in the conceptual processing of abstract and concrete concepts, while it remains to be investigated whether their representations follow different organizational principles. PMID- 22673879 TI - Impact of arterial hypertension on the eye. AB - Systemic hypertension has been linked to a wide range of major eye diseases. High arterial blood pressure (BP) decreases choroidal circulatory flow, increases intraocular pressure, and is associated with retinal microvascular abnormalities and prevalence of retinal vein occlusion (RVO) and retinopathy. This review offers a comprehensive overview of ocular diseases associated with hypertension and emphasizes their importance as predictors to future cardiovascular events. It also gives evidence-based clinical data for the therapeutic approach of eye disease in hypertensive patients. PMID- 22673882 TI - Acute kidney injury and chronic kidney disease: an integrated clinical syndrome. AB - The previous conventional wisdom that survivors of acute kidney injury (AKI) tend to do well and fully recover renal function appears to be flawed. AKI can cause end-stage renal disease (ESRD) directly, and increase the risk of developing incident chronic kidney disease (CKD) and worsening of underlying CKD. In addition, severity, duration, and frequency of AKI appear to be important predictors of poor patient outcomes. CKD is an important risk factor for the development and ascertainment of AKI. Experimental data support the clinical observations and the bidirectional nature of the relationships between AKI and CKD. Reductions in renal mass and nephron number, vascular insufficiency, cell cycle disruption, and maladaptive repair mechanisms appear to be important modulators of progression in patients with and without coexistent CKD. Distinction between AKI and CKD may be artificial. Consideration should be given to the integrated clinical syndrome of diminished GFR, with acute and chronic stages, where spectrum of disease state and outcome is determined by host factors, including the balance of adaptive and maladaptive repair mechanisms over time. Physicians must provide long-term follow-up to patients with first episodes of AKI, even if they presented with normal renal function. PMID- 22673881 TI - Lipidomic analysis of N-acylphosphatidylethanolamine molecular species in Arabidopsis suggests feedback regulation by N-acylethanolamines. AB - N-Acylphosphatidylethanolamine (NAPE) and its hydrolysis product, N acylethanolamine (NAE), are minor but ubiquitous lipids in multicellular eukaryotes. Various physiological processes are severely affected by altering the expression of fatty acid amide hydrolase (FAAH), an NAE-hydrolyzing enzyme. To determine the effect of altered FAAH activity on NAPE molecular species composition, NAE metabolism, and general membrane lipid metabolism, quantitative profiles of NAPEs, NAEs, galactolipids, and major and minor phospholipids for FAAH mutants of Arabidopsis were determined. The NAPE molecular species content was dramatically affected by reduced FAAH activity and elevated NAE content in faah knockouts, increasing by as much as 36-fold, far more than the NAE content, suggesting negative feedback regulation of phospholipase D-mediated NAPE hydrolysis by NAE. The N-acyl composition of NAPE remained similar to that of NAE, suggesting that the NAPE precursor pool largely determines NAE composition. Exogenous NAE 12:0 treatment elevated endogenous polyunsaturated NAE and NAPE levels in seedlings; NAE levels were increased more in faah knockouts than in wild-type or FAAH overexpressors. Treated seedlings with elevated NAE and NAPE levels showed impaired growth and reduced galactolipid synthesis by the "prokaryotic" (i.e., plastidic), but not the "eukaryotic" (i.e., extraplastidic), pathway. Overall, our data provide new insights into the regulation of NAPE-NAE metabolism and coordination of membrane lipid metabolism and seedling development. PMID- 22673883 TI - Signaling through the interleukin-18 receptor alpha attenuates inflammation in cisplatin-induced acute kidney injury. AB - Interleukin (IL)-18 is produced by leukocytes and renal parenchymal cells (tubular epithelial cells, podocytes, and mesangial cells). The IL-18 receptor (IL-18R) is expressed on these cells in cisplatin-induced acute kidney injury, but the role of IL-18R is unknown. To help define this, we compared IL-18Ralpha knockout with wild-type mice in cisplatin-induced acute kidney injury and found deteriorated kidney function, tubular damage, increased accumulation of leukocytes (CD4(+) and CD8(+) T-cells, macrophages, and neutrophils), upregulation of early kidney injury biomarkers (serum TNF, urinary IL-18, and KIM 1 levels), and increased expression of pro-inflammatory molecules downstream of IL-18. In vitro, leukocytes from the spleen and kidneys of the knockout mice produced greater amounts of pro-inflammatory cytokines upon stimulation with concanavalin A compared to that in wild-type mice. Levels of the suppressor of cytokine signaling 1 and 3 (negative regulators of cytokine signaling) were reduced in the spleen and kidneys of IL-18Ralpha-deficient compared to wild-type mice. Adoptive transfer of wild-type splenocytes by IL-18Ralpha-deficient mice led to decreased cisplatin nephrotoxicity compared to control IL-18Ralpha deficient mice. In contrast, anti-IL-18Ralpha and anti-IL-18Rbeta antibody treatment tended to increase cisplatin nephrotoxicity in wild-type mice. Thus, signaling through IL-18Ralpha activates both inflammation-suppressing and pro injury pathways in cisplatin-induced acute kidney injury. PMID- 22673884 TI - The Iranian model of living renal transplantation. AB - Organ shortage for transplantation remains a worldwide serious problem for kidney patients with end-stage renal failure, and several countries have tried different models to address this issue. Iran has 20 years of experience with one such model that involves the active role of the government and charity foundations. Patients with a desperate demand for a kidney have given rise to a black market of brokers and other forms of organ commercialism only accessible to those with sufficient financial resources. The current Iranian model has enabled most of the Iranian kidney transplant candidates, irrespective of socioeconomic class, to have access to kidney transplantation. The Iranian government has committed a large budget through funding hospital and staff at the Ministry of Health and Medical Education by supporting the brain death donation (BDD) program or redirecting part of the budget of living unrelated renal donation (LURD) to the BDD program. It has been shown that it did not prevent the development and progression of a BDD program. However, the LURD program is characterized by several controversial procedures (e.g., confrontation of donor and recipient at the end of the evaluation procedure along with some financial interactions) that should be ethically reviewed. Operational weaknesses such as the lack of a registration system and long-term follow-up of the donors are identified as the 'Achilles heel of the model'. PMID- 22673885 TI - Enhanced expression of the M-type phospholipase A2 receptor in glomeruli correlates with serum receptor antibodies in primary membranous nephropathy. AB - The M-type phospholipase A2 receptor (PLA2R) is the major target antigen in idiopathic membranous nephropathy with detectable autoantibodies in the serum of up to 70% of patients. In retrospective studies, the PLA2R-autoantibody titer in the serum was sometimes negative indicating their measurement alone may be inconclusive. In order to better differentiate between primary and secondary membranous nephropathy, we conducted a prospective study that included 88 patients with a histologic diagnosis of membranous nephropathy. Immunohistochemical analysis for PLA2R was faintly positive in kidneys from normal individuals and patients with various other glomerular injuries. In 61 of the 88 patients, PLA2R expression was strongly positive in glomeruli, and in 60 of these patients PLA2R autoantibodies were also detected in the serum. The 27 patients negative for serum PLA2R autoantibodies were faintly positive for PLA2R staining in glomeruli and in 15 of these patients a secondary cause was found. The remaining 12 patients have a yet undetected secondary cause of membranous nephropathy or have different glomerular antigens other than PLA2R. Thus, increased staining for PLA2R in glomeruli of renal biopsies tightly correlates with the presence of PLA2R autoantibodies in the serum and this may help discriminate between primary and secondary membranous nephropathy. PMID- 22673886 TI - Macrophage/monocyte depletion by clodronate, but not diphtheria toxin, improves renal ischemia/reperfusion injury in mice. AB - The role of resident renal mononuclear phagocytes in acute kidney injury is controversial with experimental data suggesting both deleterious and protective functions. To help resolve this, we used mice transgenic for the human diphtheria toxin receptor under the control of the CD11b promoter and treated them with diphtheria toxin, or liposomal clodronate, or both to deplete monocyte/mononuclear phagocytes prior to renal ischemia/reperfusion injury. Although either system effectively depleted circulating monocytes and resident mononuclear phagocytes, depletion was most marked in diphtheria toxin-treated mice. Despite this, diphtheria toxin treatment did not protect from renal ischemia. In contrast, mice treated with clodronate exhibited reduced renal failure and acute tubular necrosis, suggesting key differences between these depletion strategies. Clodronate did not deplete CD206-positive renal macrophages and, unlike diphtheria toxin, left resident CD11c-positive cells unscathed while inducing dramatic apoptosis in hepatic and splenic mononuclear phagocyte populations. Abolition of the protected phenotype by administration of diphtheria toxin to clodronate-treated mice suggested that the protective effect of clodronate resulted from the presence of a cytoprotective intrarenal population of mononuclear phagocytes sensitive to diphtheria toxin-mediated ablation. PMID- 22673887 TI - C3 glomerulonephritis: clinicopathological findings, complement abnormalities, glomerular proteomic profile, treatment, and follow-up. AB - C3 glomerulonephritis (C3GN) is a recently described disorder that typically results from abnormalities in the alternative pathway (AP) of complement. Here, we describe the clinical features, kidney biopsy findings, AP abnormalities, glomerular proteomic profile, and follow-up in 12 cases of C3GN. This disorder equally affected all ages, both genders, and typically presented with hematuria and proteinuria. In both the short and long term, renal function remained stable in the majority of patients with native kidney disease. In two patients, C3GN recurred within 1 year of transplantation and resulted in a decline in allograft function. Kidney biopsy mainly showed a membranoproliferative pattern, although both mesangial proliferative and diffuse endocapillary proliferative glomerulonephritis were noted. AP abnormalities were heterogeneous, both acquired and genetic. The most common acquired abnormality was the presence of C3 nephritic factors, while the most common genetic finding was the presence of H402 and V62 alleles of Factor H. In addition to these risk factors, other abnormalities included Factor H autoantibodies and mutations in CFH, CFI, and CFHR genes. Laser dissection and mass spectrometry of glomeruli from patients with C3GN showed accumulation of AP and terminal complement complex proteins. Thus, C3GN results from diverse abnormalities of the alternative complement pathway leading to subsequent glomerular injury. PMID- 22673888 TI - The level of galactose-deficient IgA1 in the sera of patients with IgA nephropathy is associated with disease progression. AB - Although high serum levels of galactose-deficient IgA1 (an important biomarker of IgA nephropathy (IgAN)) are found in most patients with IgAN, their relationship to disease severity and progression remains unclear. To help clarify this we prospectively enrolled 275 patients with IgAN and followed them for a median of 47 months (range 12-96 months). Serum galactose-deficient IgA1 was measured at the time of diagnosis using a lectin-based ELISA, and renal survival was modeled using the Cox proportional hazards method. The serum levels of galactose deficient IgA1 were higher in patients with IgAN compared to those in healthy controls. Importantly, in adjusted analysis, higher levels of galactose-deficient IgA1 were independently associated with a greater risk of deterioration in renal function with a hazard ratio of 1.44 per standard deviation of the natural log transformed galactose-deficient IgA1 concentration. In reference to the first quartile, the risk of kidney failure increased such that the hazard ratio for the second quartile was 2.47, 3.86 for the third, and 4.76 for the fourth quartile of the galactose-deficient IgA1 concentration. Hence, elevated serum levels of galactose-deficient IgA1 are associated with a poor prognosis in IgAN. PMID- 22673889 TI - Abrogation of lectin-like oxidized LDL receptor-1 attenuates acute myocardial ischemia-induced renal dysfunction by modulating systemic and local inflammation. AB - It is assumed that acute myocardial infarction affects renal function. To study the mechanism, we used mice following permanent ligation of their left coronary artery that results in extensive myocardial infarction. Soon after ligation, there was a marked rise in circulating pro-inflammatory cytokines and malondialdehyde (thiobarbituric acid-positive evidence of lipid peroxidation). Renal function had significantly declined by the third day in association with mild fibrosis, and swelling of glomeruli and tubules. There was a significant increase in the expression of the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), interelukin-1beta, vascular cell adhesion molecule-1, and thiobarbituric acid-reactive substances in the kidney. Renal function showed some recovery by Day 21; however, there was progressive fibrosis of the kidneys. LOX-1 knockout mice had significantly diminished increases in systemic and renal pro inflammatory cytokines, malondialdehyde, structural alterations, and decline in renal function than the wild-type mice following ligation of the left coronary artery. Cardiac function and survival rates were also significantly better in the LOX-1 knockout mice than in the wild-type mice. Hence, severe myocardial ischemia results in renal dysfunction and histological abnormalities suggestive of acute renal injury. Thus, LOX-1 is a key modulator among multiple mechanisms underlying renal dysfunction following extensive myocardial infarction. PMID- 22673890 TI - Mast cell activation and degranulation promotes renal fibrosis in experimental unilateral ureteric obstruction. AB - Progressive renal fibrosis is the final common pathway leading to renal failure irrespective of the initiating cause. Clinical studies of renal fibrosis found that prominent mast cell accumulation correlated with worse outcomes. Mast cells are pluripotent innate immune cells that synthesize and secrete profibrotic mediators. Here we use mast cell-deficient (Kit(W-sh/W-sh)) mice to define a functional pathogenic role for these cells in the development of renal fibrosis. Intrarenal collagen deposition was significantly decreased in mast cell-deficient compared to wild-type mice 7 and 14 days after unilateral ureteric obstruction. The intrarenal expression of mRNAs for transforming growth factor-beta, alpha smooth muscle actin, chemokines, and renal macrophages and CD4(+) T cells were also decreased in mast cell-deficient mice. Reconstitution of the mast cell population in mast cell-deficient mice with wild-type bone marrow-derived mast cells restored the pattern and intensity of renal fibrosis to levels seen in wild type mice following ureteric ligation. Interestingly, the mast cells were recruited, activated, and degranulated within 6 h of ureteric ligation. A mast cell stabilizer that impairs degranulation, disodium chromoglycate, significantly attenuated renal fibrosis following ureteric ligation in wild-type mice. Thus, mast cells promote renal fibrosis and their targeting may offer therapeutic potential in the treatment of renal fibrosis. PMID- 22673891 TI - Highly selective and sensitive fluorescent sensing of oxalate in water. AB - Effective fluorescent sensing of oxalate in water is significant but still remains a challenge. By using indicator-displacement assays, a readily available macrocyclic copper(II) complex was found to show a sensitive off-on fluorescent sensing for oxalate with high selectivity and high binding affinity (>10(7) M( 1)) in water at neutral pH. PMID- 22673892 TI - An efficient and secure dynamic ID-based authentication scheme for telecare medical information systems. AB - The rapidly increased availability of always-on broadband telecommunication environments and lower-cost vital signs monitoring devices bring the advantages of telemedicine directly into the patient's home. Hence, the control of access to remote medical servers' resources has become a crucial challenge. A secure authentication scheme between the medical server and remote users is therefore needed to safeguard data integrity, confidentiality and to ensure availability. Recently, many authentication schemes that use low-cost mobile devices have been proposed to meet these requirements. In contrast to previous schemes, Khan et al. proposed a dynamic ID-based remote user authentication scheme that reduces computational complexity and includes features such as a provision for the revocation of lost or stolen smart cards and a time expiry check for the authentication process. However, Khan et al.'s scheme has some security drawbacks. To remedy theses, this study proposes an enhanced authentication scheme that overcomes the weaknesses inherent in Khan et al.'s scheme and demonstrated this scheme is more secure and robust for use in a telecare medical information system. PMID- 22673893 TI - An emergency system to improve ambulance dispatching, ambulance diversion and clinical handover communication-a proposed model. AB - Effective communication in healthcare is important and especially critical in emergency situations. In this paper we propose a new comprehensive emergency system which facilitates the communication process in emergency cases from ambulance dispatch to the patient's arrival and handover in the hospital. The proposed system has been designed to facilitate and computerize all the processes involved in an accident from finding the nearest ambulance through to accessing a patient's online health record which can assist in pre-hospital treatments. The proposed system also locates the nearest hospital specializing in the patient's condition and will communicate patient identification to the emergency department. The components of the proposed system and the technologies used in building this system are outlined in this paper as well as the challenges expected and proposed solutions to these challenges. PMID- 22673894 TI - Elimination of motion and pulsation artifacts using BLADE sequences in knee MR imaging. AB - The purpose of this study is to evaluate the ability of proton density (PD)-BLADE sequences in reducing or even eliminating motion and pulsatile flow artifacts in knee magnetic resonance imaging examinations. Eighty consecutive patients, who had been routinely scanned for knee examination, participated in the study. The following pairs of sequences with and without BLADE were compared: (a) PD turbo spin echo (TSE) sagittal (SAG) fat saturation (FS) in 35 patients, (b) PD TSE coronal (COR) FS in 19 patients, (c) T2 TSE axial in 13 patients and (d) PD TSE SAG in 13 patients. Both qualitative and quantitative analyses were performed based on the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and relative contrast (ReCon) measures of normal anatomic structures. The qualitative analysis was performed by experienced radiologists. Also, the presence of image motion and pulsation artifacts was evaluated. Based on the results of the SNR, CRN and ReCon for the different sequences and anatomical structures, the BLADE sequences were significantly superior in 19 cases, whereas the corresponding conventional sequences were significantly superior in only 6 cases. BLADE sequences eliminated motion artifacts in all the cases. However, motion artifacts were shown in (a) six PD TSE SAG FS, (b) three PD TSE COR FS, (c) three PD TSE SAG and (d) two T2 TSE axial conventional sequences. In our results, it was found that, in PD FS sequences (sagittal and coronal), the differences between the BLADE and conventional sequences regarding the elimination of motion and pulsatile flow artifacts were statistically significant. In all the comparisons, the PD FS BLADE sequences (coronal and sagittal) were significantly superior to the corresponding conventional sequences regarding the classification of their image quality. In conclusion, this technique appears to be capable to potentially eliminate motion and pulsatile flow artifacts in MR images. PMID- 22673895 TI - Metabolic profile of dystrophic mdx mouse muscles analyzed with in vitro magnetic resonance spectroscopy (MRS). AB - Duchenne muscular dystrophy (DMD) is a recessive X-linked form of muscular dystrophy characterized by progressive and irreversible degeneration of the muscles. The mdx mouse is the classical animal model for DMD, showing similar molecular and protein defects. The mdx mouse, however, does not show significant muscle weakness, and the diaphragm muscle is significantly more degenerated than skeletal muscles. In this work, (1)H magnetic resonance spectroscopy (MRS) was used to study the metabolic profile of quadriceps and diaphragm muscles from mdx and control mice. Using principal components analysis (PCA), the animals were separated into groups according to age and lineages. The classification was compared to histopathological analysis. Among the 24 metabolites identified from the nuclear MR spectra, only 19 were used by the PCA program for classification purposes. These can be important key biomarkers associated with the progression of degeneration in mdx muscles and with natural aging in control mice. Glutamate, glutamine, succinate, isoleucine, acetate, alanine and glycerol were increased in mdx samples as compared to control mice, in contrast to carnosine, taurine, glycine, methionine and creatine that were decreased. These results suggest that MRS associated with pattern recognition analysis can be a reliable tool to assess the degree of pathological and metabolic alterations in the dystrophic tissue, thereby affording the possibility of evaluation of beneficial effects of putative therapies. PMID- 22673896 TI - The impact of sampling density upon cortical network analysis: regions or points. AB - The choice of representation has a fundamental influence on the network analysis results of an empirical data set. The answers to two basic questions - how to define a node and how to define an edge between a pair of nodes - are not obvious in the network analysis of brain imaging data. We considered the first question in the case of magnetic resonance imaging (MRI)-based cortical thickness networks. We selected network nodes to represent vertices of a cortical surface mesh or cortical brain regions. The first network represents the maximal level of detail available in the analysis of cortical thickness networks, while the latter network represents the typical level of detail in the current network analysis studies. We compared the network analysis results between these two representations. The basic network measures behaved approximately as expected when the level of detail increased. However, the overall connectivity of nodes was greater in the vertex level, degree of clustering was smaller in the vertex level, and the node centralities were different between the levels. Further, many parameters of vertex-level network were more robust to the selection of the correlation threshold used to define the edges of network. We conclude that albeit many qualitative network properties were consistent between the two resolution levels, the vertex-level resolution revealed details that were not visible at the regional-level networks, and this additional detail could be useful for some applications. Finally, a similar methodology as the one used here could be used to study effects of the sampling density in other brain-imaging based networks, for example, in resting-state functional MRI. PMID- 22673897 TI - Better methods will be needed to project incomes to estimate eligibility for subsidies in health insurance exchanges. AB - Under the Affordable Care Act, people who meet certain income eligibility criteria will be eligible for subsidies to offset costs of premiums and cost sharing for health insurance plans purchased through new health insurance exchanges. But determining the correct level of these subsidies will not be easy, because of several factors. These include the way in which eligibility will be calculated for participation in Medicaid or for subsidies through the exchanges; possibly inaccurate income projections; the use of different income time periods to determine eligibility; and fluctuations in income. I performed a simulation that shows that under the most likely methods to be used to determine eligibility for Medicaid or for receiving subsidies through exchanges, one-third of people with incomes initially judged to be below the Medicaid threshold would actually "churn" into an exchange at the end of the year. Other people would be wrongly deemed ineligible for advance subsidy payments because their projected income was too high, while still others judged eligible for subsidies would receive advance payments on those subsidies that were too high by $208 per year, on average. To reduce these errors, I recommend the adoption of a single eligibility standard based on income data derived from prior tax returns, along with generous accommodations during a given enrollment year for people who claim a change in circumstances, such as a change in income. PMID- 22673898 TI - Brief Report: to squeeze or not to squeeze, that is the question! Optimizing the disease activity score in 28 joints by adding the squeeze test of metatarsophalangeal joints in early rheumatoid arthritis. AB - OBJECTIVE: To optimize use of the Disease Activity Score in 28 joints (DAS28) in early rheumatoid arthritis (RA) by adding the "squeeze test" of forefeet. METHODS: The squeeze test is used to examine bilateral compression pain (BCP) across the metatarsophalangeal (MTP) joints. For this study, data for patients participating in the Treatment in the Rotterdam Early Arthritis Cohort study, an ongoing clinical trial that evaluates different induction therapies in patients with early RA, were randomly divided into 2 subsets. In subset 1 (149 patients and 819 disease activity assessments), the mathematical function of the DAS28 squeeze was constructed using a linear regression model with the DAS as the dependent variable and the DAS28 and squeeze test as the independent variables. A DAS28-BCP disease state was also constructed, in which DAS28 disease state categorizations were upgraded one state if the result of the squeeze test was positive. In subset 2 (153 patients and 754 assessments), concordance in disease states between the DAS28, DAS28-squeeze, and DAS28-BCP disease states was compared, using both the DAS and Boolean-defined remission criteria as reference. RESULTS: Agreement between the DAS and the DAS28-squeeze (82%) was significantly higher than agreement between the DAS and the DAS28 (76%). When we assessed the group of patients who had arthritis of the forefeet only (22 patients and 46 assessments), overall agreement between the DAS and the DAS28 was 40%, while agreement between the DAS and the DAS28-squeeze was 59% and that between the DAS and the DAS28-BCP disease state was 65%. Furthermore, the specificities of the DAS28-squeeze and the DAS28-BCP (80% and 81%, respectively) were higher than that of the DAS28 (76%), while the sensitivities of the DAS28, DAS28-squeeze, and DAS28-BCP to identify true remission according to the Boolean criteria were 88%, 87%, and 81%, respectively. CONCLUSION: Adding the squeeze test of forefeet to the DAS28 has value for dependably classifying the disease state in patients with early RA. PMID- 22673899 TI - Unusual CoS2 ellipsoids with anisotropic tube-like cavities and their application in supercapacitors. AB - Unusual CoS(2) ellipsoids with anisotropic tube-like cavities have been synthesized from the simultaneous thermal decomposition and sulfidation of a preformed cobalt carbonate precursor. The as-prepared CoS(2) ellipsoids show interesting supercapacitive properties with high capacitance and good cycling performance. PMID- 22673900 TI - Major respiratory adverse events after laparascopic gastric banding surgery for morbid obesity. AB - BACKGROUND: Laparoscopic adjustable gastric banding surgery has become one of the most common restrictive surgical procedures for treatment of morbid obesity worldwide. Although short-term respiratory complications are well known, long term data is scarce. We investigated the manifestations of major pulmonary complications showed at least six months after the procedure. METHODS: A retrospective cohort study was conducted at a tertiary university medical center in the five years period of 2006-2010. We included every patient who had had major respiratory complication who needed hospitalization, at least 6 months after laparoscopic adjustable gastric banding procedure. Demographic, pre operative and post-operative clinical data were collected. We documented respiratory symptoms, results of physical examination, pulmonary function tests, and imaging as well as therapies given and outcome. RESULTS: Out of 2100 patients who underwent LAGB, thirty subjects, mean age of 45.7 (range 29-64) with an equal number of males and females were included. Mean interval between operation and onset of respiratory symptoms was 51.5 months (range 10-150 months). All had dyspeptic complaints which included: regurgitation, fullness after meals, dysphagia and food aspiration with esophageal dilatation. Major respiratory complications included aspiration pneumonia (19) including pulmonary abscess (4) and empyema (2), exacerbation of asthma (3) and hemoptysis (1). Additionally we documented the emergence of chronic diseases such as interstitial lung disease (5) and bronchiectasis (3). One patient developed acute respiratory distress syndrome due to aspiration pneumonia and eventually died in the intensive care unit. The main mode of therapy was deflation of the gastric band. Those who refused to deflate or remove the gastric banding continued to suffer from dyspeptic and respiratory symptoms including recurrent pulmonary abscess. CONCLUSION: Although laparoscopic adjustable gastric banding surgery has few short-term risks and is highly effective at achieving weight reduction, we found an increased risk for major respiratory complications in the long-term period. The obesity epidemic and the increased use of surgical techniques to treat obesity will most likely lead to an increase in the incidence of long-term post operative respiratory complications. This entity is probably under-reported and needs further research into how to reduce its incidence and morbidity. PMID- 22673901 TI - Direct observation of prompt pre-thermal laser ion sheath acceleration. AB - High-intensity laser plasma-based ion accelerators provide unsurpassed field gradients in the megavolt-per-micrometer range. They represent promising candidates for next-generation applications such as ion beam cancer therapy in compact facilities. The weak scaling of maximum ion energies with the square-root of the laser intensity, established for large sub-picosecond class laser systems, motivates the search for more efficient acceleration processes. Here we demonstrate that for ultrashort (pulse duration ~30 fs) highly relativistic (intensity ~10(21) W cm(-2)) laser pulses, the intra-pulse phase of the proton acceleration process becomes relevant, yielding maximum energies of around 20 MeV. Prominent non-target-normal emission of energetic protons, reflecting an engineered asymmetry in the field distribution of promptly accelerated electrons, is used to identify this pre-thermal phase of the acceleration. The relevant timescale reveals the underlying physics leading to the near-linear intensity scaling observed for 100 TW class table-top laser systems. PMID- 22673902 TI - Differentiation of multipotent vascular stem cells contributes to vascular diseases. AB - It is generally accepted that the de-differentiation of smooth muscle cells, from the contractile to the proliferative/synthetic phenotype, has an important role during vascular remodelling and diseases. Here we provide evidence that challenges this theory. We identify a new type of stem cell in the blood vessel wall, named multipotent vascular stem cells. Multipotent vascular stem cells express markers, including Sox17, Sox10 and S100beta, are cloneable, have telomerase activity, and can differentiate into neural cells and mesenchymal stem cell-like cells that subsequently differentiate into smooth muscle cells. On the other hand, we perform lineage tracing with smooth muscle myosin heavy chain as a marker and find that multipotent vascular stem cells and proliferative or synthetic smooth muscle cells do not arise from the de-differentiation of mature smooth muscle cells. In response to vascular injuries, multipotent vascular stem cells, instead of smooth muscle cells, become proliferative, and differentiate into smooth muscle cells and chondrogenic cells, thus contributing to vascular remodelling and neointimal hyperplasia. These findings support a new hypothesis that the differentiation of multipotent vascular stem cells, rather than the de differentiation of smooth muscle cells, contributes to vascular remodelling and diseases. PMID- 22673903 TI - Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues. AB - Deregulated cellular signalling is a common hallmark of disease, and delineating tissue phosphoproteomes is key to unravelling the underlying mechanisms. Here we present the broadest tissue catalogue of phosphoproteins to date, covering 31,480 phosphorylation sites on 7,280 proteins quantified across 14 rat organs and tissues. We provide the data set as an easily accessible resource via a web-based database, the CPR PTM Resource. A major fraction of the presented phosphorylation sites are tissue-specific and modulate protein interaction networks that are essential for the function of individual organs. For skeletal muscle, we find that phosphotyrosines are over-represented, which is mainly due to proteins involved in glycogenolysis and muscle contraction, a finding we validate in human skeletal muscle biopsies. Tyrosine phosphorylation is involved in both skeletal and cardiac muscle contraction, whereas glycogenolytic enzymes are tyrosine phosphorylated in skeletal muscle but not in the liver. The presented phosphoproteomic method is simple and rapid, making it applicable for screening of diseased tissue samples. PMID- 22673904 TI - Loss-of-function of inositol polyphosphate-4-phosphatase reversibly increases the severity of allergic airway inflammation. AB - Inositol polyphosphate phosphatases regulate the magnitude of phosphoinositide-3 kinase signalling output. Although inositol polyphosphate-4-phosphatase is known to regulate phosphoinositide-3 kinase signalling, little is known regarding its role in asthma pathogenesis. Here we show that modulation of inositol polyphosphate-4-phosphatase alters the severity of asthma. Allergic airway inflammation in mice led to calpain-mediated degradation of inositol polyphosphate-4-phosphatase. In allergic airway inflammation models, preventing inositol polyphosphate-4-phosphatase degradation by inhibiting calpain activity, or overexpression of inositol polyphosphate-4-phosphatase in mouse lungs, led to attenuation of the asthma phenotype. Conversely, knockdown of inositol polyphosphate-4-phosphatase severely aggravated the allergic airway inflammation and the asthma phenotype. Interestingly, inositol polyphosphate-4-phosphatase knockdown in lungs of naive mice led to spontaneous airway hyper-responsiveness, suggesting that inositol polyphosphate-4-phosphatase could be vital in maintaining the lung homeostasis. We suggest that inositol polyphosphate-4 phosphatase has an important role in modulating inflammatory response in asthma, and thus, uncover a new understanding of the complex interplay between inositol signalling and asthma, which could provide alternative strategies in asthma management. PMID- 22673906 TI - Anomalous high capacitance in a coaxial single nanowire capacitor. AB - Building entire multiple-component devices on single nanowires is a promising strategy for miniaturizing electronic applications. Here we demonstrate a single nanowire capacitor with a coaxial asymmetric Cu-Cu(2)O-C structure, fabricated using a two-step chemical reaction and vapour deposition method. The capacitance measured from a single nanowire device corresponds to ~140 MUF cm(-2), exceeding previous reported values for metal-insulator-metal micro-capacitors and is more than one order of magnitude higher than what is predicted by classical electrostatics. Quantum mechanical calculations indicate that this unusually high capacitance may be attributed to a negative quantum capacitance of the dielectric metal interface, enhanced significantly at the nanoscale. PMID- 22673905 TI - Structure and mechanism of a canonical poly(ADP-ribose) glycohydrolase. AB - Poly(ADP-ribosyl)ation is a reversible post-translational protein modification involved in the regulation of a number of cellular processes including DNA repair, chromatin structure, mitosis, transcription, checkpoint activation, apoptosis and asexual development. The reversion of poly(ADP-ribosyl)ation is catalysed by poly(ADP-ribose) (PAR) glycohydrolase (PARG), which specifically targets the unique PAR (1''-2') ribose-ribose bonds. Here we report the structure and mechanism of the first canonical PARG from the protozoan Tetrahymena thermophila. In addition, we reveal the structure of T. thermophila PARG in a complex with a novel rhodanine-containing mammalian PARG inhibitor RBPI-3. Our data demonstrate that the protozoan PARG represents a good model for human PARG and is therefore likely to prove useful in guiding structure-based discovery of new classes of PARG inhibitors. PMID- 22673907 TI - Digital quantum simulation of the statistical mechanics of a frustrated magnet. AB - Many problems of interest in physics, chemistry and computer science are equivalent to problems defined on systems of interacting spins. However, most such problems require computational resources that are out of reach with classical computers. A promising solution to overcome this challenge is quantum simulation. Several 'analogue' quantum simulations of interacting spin systems have been realized experimentally, where ground states were prepared using adiabatic techniques. Here we report a 'digital' quantum simulation of thermal states; a three-spin frustrated magnet was simulated using a nuclear magnetic resonance quantum information processor, and we were able to explore the phase diagram of the system at any simulated temperature and external field. These results help to identify the challenges for performing quantum simulations of physical systems at finite temperatures, and suggest methods that may be useful in simulating thermal open quantum systems. PMID- 22673908 TI - Estimating the potential public health impact of seasonal malaria chemoprevention in African children. AB - Seasonal malaria chemoprevention, previously known as intermittent preventive treatment in children, is highly effective in areas with a short malaria transmission season. Here we assess seasonality in malaria incidence data and define a predictor of seasonality based on rainfall. We then use spatial rainfall, malaria endemicity and population data to identify areas likely to have highly seasonal malaria incidence, and estimate the population at risk and malaria burden in areas where seasonal malaria chemoprevention would be appropriate. We estimate that in areas suitable for seasonal malaria chemoprevention, there are 39 million children under 5 years of age, who experience 33.7 million malaria episodes and 152,000 childhood deaths from malaria each year. The majority of this burden occurs in the Sahelian or sub Sahelian regions of Africa. Our data suggest that seasonal malaria chemoprevention has the potential to avert several million malaria cases and tens of thousands of childhood deaths each year if successfully delivered to the populations at risk. PMID- 22673909 TI - Observation of topologically protected bound states in photonic quantum walks. AB - Topological phases exhibit some of the most striking phenomena in modern physics. Much of the rich behaviour of quantum Hall systems, topological insulators, and topological superconductors can be traced to the existence of robust bound states at interfaces between different topological phases. This robustness has applications in metrology and holds promise for future uses in quantum computing. Engineered quantum systems--notably in photonics, where wavefunctions can be observed directly--provide versatile platforms for creating and probing a variety of topological phases. Here we use photonic quantum walks to observe bound states between systems with different bulk topological properties and demonstrate their robustness to perturbations--a signature of topological protection. Although such bound states are usually discussed for static (time-independent) systems, here we demonstrate their existence in an explicitly time-dependent situation. Moreover, we discover a new phenomenon: a topologically protected pair of bound states unique to periodically driven systems. PMID- 22673910 TI - Alternative splicing of CD44 mRNA by ESRP1 enhances lung colonization of metastatic cancer cell. AB - In cancer metastasis, various environmental stressors attack the disseminating cells. The successful colonization of cancer cells in secondary sites therefore requires the ability of the cells to avoid the consequences of such exposure to the stressors. Here we show that orthotopic transplantation of a CD44 variant isoform-expressing (CD44v(+)) subpopulation of 4T1 breast cancer cells, but not that of a CD44v(-) subpopulation, in mice results in efficient lung metastasis accompanied by expansion of stem-like cancer cells. Such metastasis is dependent on the activity of the cystine transporter xCT, and the stability of this protein is controlled by CD44v. We find that epithelial splicing regulatory protein 1 regulates the expression of CD44v, and knockdown of epithelial splicing regulatory protein 1 in CD44v(+) cells results in an isoform switch from CD44v to CD44 standard (CD44s), leading to reduced cell surface expression of xCT and suppression of lung colonization. The epithelial splicing regulatory protein 1 CD44v-xCT axis is thus a potential therapeutic target for the prevention of metastasis. PMID- 22673912 TI - Unfavourable environment limits social conflict in Yuhina brunneiceps. AB - Identifying the factors that modulate cooperative and competitive behaviours is the key to understanding social evolution. However, how ecological factors affect social conflict and their fitness consequences remain relatively unexplored. Here, using both a game-theoretical model and empirical data, we show that Taiwan yuhinas (Yuhina brunneiceps)--a joint-nesting species in which group members are unrelated--employ more cooperative strategies in unfavourable environmental conditions. Fighting duration was lower, fewer total eggs were laid and incubation was more likely to start after all females completed egg laying (which causes more synchronous egg hatching). Surprisingly, as a consequence, there were more surviving offspring in unfavourable conditions because the cooperative strategies resulted in fewer dead nestlings. To our knowledge, this study is the first theoretical analysis and empirical study demonstrating that an unfavourable environment reduces social conflict and results in better fitness consequences in social vertebrates. PMID- 22673911 TI - Melanoma induction by ultraviolet A but not ultraviolet B radiation requires melanin pigment. AB - Malignant melanoma of the skin (CMM) is associated with ultraviolet radiation exposure, but the mechanisms and even the wavelengths responsible are unclear. Here we use a mammalian model to investigate melanoma formed in response to precise spectrally defined ultraviolet wavelengths and biologically relevant doses. We show that melanoma induction by ultraviolet A (320-400 nm) requires the presence of melanin pigment and is associated with oxidative DNA damage within melanocytes. In contrast, ultraviolet B radiation (280-320 nm) initiates melanoma in a pigment-independent manner associated with direct ultraviolet B DNA damage. Thus, we identified two ultraviolet wavelength-dependent pathways for the induction of CMM and describe an unexpected and significant role for melanin within the melanocyte in melanomagenesis. PMID- 22673913 TI - Genomics of DNA cytosine methylation in Escherichia coli reveals its role in stationary phase transcription. AB - DNA cytosine methylation regulates gene expression in mammals. In bacteria, its role in gene expression and genome architecture is less understood. Here we perform high-throughput sequencing of bisulfite-treated genomic DNA from Escherichia coli K12 to describe, for the first time, the extent of cytosine methylation of bacterial DNA at single-base resolution. Whereas most target sites (C(m)CWGG) are fully methylated in stationary phase cells, many sites with an extended CC(m)CWGG motif are only partially methylated in exponentially growing cells. We speculate that these partially methylated sites may be selected, as these are slightly correlated with the risk of spontaneous, non-synonymous conversion of methylated cytosines to thymines. Microarray analysis in a cytosine methylation-deficient mutant of E. coli shows increased expression of the stress response sigma factor RpoS and many of its targets in stationary phase. Thus, DNA cytosine methylation is a regulator of stationary phase gene expression in E. coli. PMID- 22673914 TI - Valley-selective circular dichroism of monolayer molybdenum disulphide. AB - A two-dimensional honeycomb lattice harbours a pair of inequivalent valleys in the k-space electronic structure, in the vicinities of the vertices of a hexagonal Brillouin zone, K(+/-). It is particularly appealing to exploit this emergent degree of freedom of charge carriers, in what is termed 'valleytronics'. The physics of valleys mimics that of spin, and will make possible devices, analogous to spintronics, such as valley filter and valve, and optoelectronic Hall devices, all very promising for next-generation electronics. The key challenge lies with achieving valley polarization, of which a convincing demonstration in a two-dimensional honeycomb structure remains evasive. Here we show, using first principles calculations, that monolayer molybdenum disulphide is an ideal material for valleytronics, for which valley polarization is achievable via valley-selective circular dichroism arising from its unique symmetry. We also provide experimental evidence by measuring the circularly polarized photoluminescence on monolayer molybdenum disulphide, which shows up to 50% polarization. PMID- 22673915 TI - Electric-field control of magnetic domain-wall velocity in ultrathin cobalt with perpendicular magnetization. AB - Controlling the displacement of a magnetic domain wall is potentially useful for information processing in magnetic non-volatile memories and logic devices. A magnetic domain wall can be moved by applying an external magnetic field and/or electric current, and its velocity depends on their magnitudes. Here we show that the applying an electric field can change the velocity of a magnetic domain wall significantly. A field-effect device, consisting of a top-gate electrode, a dielectric insulator layer, and a wire-shaped ferromagnetic Co/Pt thin layer with perpendicular anisotropy, was used to observe it in a finite magnetic field. We found that the application of the electric fields in the range of +/- 2-3 MV cm( 1) can change the magnetic domain wall velocity in its creep regime (10(6)-10(3) m s(-1)) by more than an order of magnitude. This significant change is due to electrical modulation of the energy barrier for the magnetic domain wall motion. PMID- 22673916 TI - A polychromatic approach to far-field superlensing at visible wavelengths. AB - Breaking the diffraction barrier in the visible part of the electromagnetic spectrum is of fundamental importance. Far-field subwavelength focusing of light could, for instance, drastically broaden the possibilities available in nanolithography, light-matter interactions and sensing at the nanoscale. Similarly, imaging with a nanometric resolution could result in incredible breakthroughs in soft matter and biology. There have been numerous proposals in this regard based on metamaterials, structured illumination methods or diffractive optical components. The common denominator of all these approaches resides in their monochromatic nature. Here we show that using polychromatic light in dispersive metamaterials allows us to circumvent many limitations associated with previous monochromatic approaches. We design a plasmonic metalens based on metallic nanorods that, when used with broadband light fields, can beat the diffraction limit for imaging and focusing from the far field. PMID- 22673918 TI - Dietary vitamin C and E modulates antioxidant levels in blood, brain, liver, muscle, and testes in diabetic aged rats. AB - While tissue dysfunction is a well-recognized consequence of diabetes mellitus in aged people, the underlying mechanisms are poorly understood. Daily (VCE) supplementation of vitamins C and E can be beneficial to diabetic aged animals in reducing free radical production. The aim of this study was to investigate whether dietary VCE supplementation modulates oxidative stress and antioxidant redox systems in streptozotocin (STZ)-induced aged diabetic rats. Thirty aged rats (18 - 20 months) were randomly divided into three groups. The first group acted as a control and the second group was diabetic. VCE-supplemented feed was given to aged, diabetic rats, constituting the third group. Diabetes was induced using a single dose of intraperitoneal STZ. On the 21(st) day after STZ dosage, blood and tissue samples were taken from all animals. Glutathione peroxidase activity in liver, erythrocytes, muscle, and testes; catalase activity in plasma and erythrocytes; reduced glutathione levels in plasma; vitamin E concentration in plasma, liver, and muscle; b-carotene concentration in brain; and high-density lipoprotein (HDL)-cholesterol levels in plasma were lower in the diabetic group than in the control group. Lipid peroxidation (LP) levels in plasma, liver, brain, and muscle, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), triacyglycerols, and total and low-density lipoprotein (LDL)-cholesterol values in plasma were higher in the diabetic group than in the control group. The LP, enzyme, vitamin, and lipid profile values levels were mostly restored by VCE treatment. Liver and testis weights did not change by diabetic status and VCE supplementation, although body weight was lower in the diabetic group than in the control group. In conclusion, brain, liver, and testes tissues seem most sensitive in aged diabetic rats to oxidative stress. We observed that VCE supplementation relieves oxidative stress in the blood and tissues of diabetic aged rats by modulating the antioxidant system and lipid profile. PMID- 22673919 TI - Direct inhibition of osteoclast formation and activity by the vitamin E isomer gamma-tocotrienol. AB - Vitamin E homologues, specifically tocotrienols, have been shown to have favorable effects on bone. They possess properties that are indicative of anti resorptive activity, suggesting the potential for vitamin E in preventing bone loss. To investigate the anti-resorptive activity of the various vitamin E homologues, we cultured human osteoclasts from blood-derived CD14+ cells on collagen, dentin, and calcium phosphate substrates, with some samples supplemented with vitamin E homologues in their cell culture medium. These were compared to the clinically used bisphosphonate, pamidronate. Compounds were either added at the start of culture to study effects on osteoclast formation, or at the start of osteoclastic resorption to determine their effects on activity. The alpha- and gamma-tocotrienol isomers inhibited osteoclast formation without consequent reduction in total cell number. Only gamma-tocotrienol inhibited osteoclast activity without toxicity. Gamma-tocotrienol was the most potent inhibitor of both osteoclast formation and activity and requires further investigation into its anti-resorptive effects on bone. PMID- 22673920 TI - Antioxidant capacity of breast milk of mothers who delivered prematurely is higher than that of mothers who delivered at term. AB - BACKGROUND: The total antioxidant capacity of plasma of preterm infants has been suggested to be lower than that of term infants. The objective of this study was to compare the total antioxidant capacity of the breast milk of mothers who delivered prematurely with that of mothers who delivered at term. MATERIALS AND METHODS: A total of 71 breast milk samples were collected, 41 from mothers who delivered preterm (27 to 37 weeks) and 30 from mothers who delivered at term (38 to 42 weeks). RESULTS: The mean total antioxidant capacity of the breast milk of mothers who delivered prematurely was higher (2.19 +/- 0.88 mmol/L) than that of mothers who delivered at term (1.7 +/- 0.86 mmol/L) (p = 0.024). CONCLUSION: Breastfeeding may protect preterm infants against oxidative stress and related disorders in the neonatal period. PMID- 22673921 TI - Apple pectin affects the efficacy of epigallocatechin gallate on oral sucrose tolerance test in adult mice. AB - Epigallocatechin gallate (EGCg), a dietary polyphenol and a major tea catechin, is a known sucrase inhibitor. Since dietary pectin is known to modulate some of the functions of the gastrointestinal tract, we investigated whether it could specifically affect the efficacy of EGCg on an oral sucrose tolerance test in mice. Male Crj:CD-1 (ICR) mice (seven weeks old) were randomly divided into two groups and fed a 5 % apple pectin (PE) or 5 % cellulose (CE) diet (control diet) for 28 days. After the experimental diet period, all mice were fasted overnight. A volume of 0.2 mL EGCg (20 mg/mL) was orally administered to all the mice by stainless steel feeding needle via injection syringe and a sucrose tolerance test was performed. The blood glucose levels were measured in blood collected from the tail vein using the OneTouch(r) Ultra(r) blood glucose monitoring system. Blood glucose levels at 30 minutes and 60 minutes after sucrose loading in the PE group were significantly higher than initial blood glucose levels. However, blood glucose levels at 30 minutes, 60 minutes, and 120 minutes after sucrose loading in the CE group were not significantly higher than initial blood glucose levels. After laparotomy, plasma lipids were also measured. Plasma triglyceride concentrations were significantly greater in the PE group than in the CE (control) group. This demonstrates that dietary pectin can affect the efficacy of EGCg on the oral sucrose tolerance test in mice. PMID- 22673922 TI - Effect of curcumin on LDL oxidation in vitro, and lipid peroxidation and antioxidant enzymes in cholesterol fed rabbits. AB - In this study we examined the antioxidant effect of curcumin on lipid oxidation in vitro and in vivo. In vitro, curcumin at 5 microgM concentration completely prevented low-density lipoprotein (LDL) oxidation by CuS0(4), indicating that curcumin is an effective antioxidant in vitro. In vivo, feeding a pure cholesterol (PC)-rich diet to rabbits significantly increased the plasma and liver lipids as well as thiobarbituric acid reactive substances (TBARS) levels. Addition of curcumin to the PC diet did not show any effect on either plasma lipid and TBARS or liver lipids. Liver TBARS tended to decrease but that decrease was not significant. Erythrocyte glutathione peroxidase (GSH-Px) activity was significantly decreased while catalase activity was significantly increased in rabbits fed a PC diet. The addition of curcumin to a PC diet did not show any significant effect on erythrocyte enzyme activities compared to the rabbits fed a PC diet. The liver GSH-Px and catalase activities were significantly decreased in rabbits fed a PC diet, but the addition of curcumin to the PC diet enhanced the liver GSH-Px activity, which became nonsignificantly different from the control group. These results were discussed considering that curcumin may not be well absorbed and it did not reach a level high enough in vivo to overcome the severe hypercholesterolemia and oxidative stress produced by the PC-rich diet. PMID- 22673923 TI - An association study of SNP + 45 T > G of the AdipoQ gene with type 2 diabetes in Yi and Han people in China. AB - BACKGROUND: The Yi people are considered the most primitive society in China, and live in the remote mountainous areas of Southwestern China. There have been no previous publications on genetic research concerning type 2 diabetes (T2D) in the Yi people. This is the first report that presents the association between SNP + 45 T > G (rs2241766) of the AdipoQ gene and T2D in Yi people. Our previous study showed that the prevalence of T2D in Yi people was lower than the national level in 2008. Genetic differences between Yi and Han people might be one possible explanation for this observation. Studies on the single nucleotide polymorphism SNP + 45 T > G (rs2241766) of the AdipoQ gene in Chinese Han people showed inconsistent results. This study was designed to identify genetic variants of the AdipoQ gene that contribute to the development of T2D in Yi and Han people. METHODS: A case-control study on the association between SNP + 45 T > G (rs2241766) of the AdipoQ gene and T2D was carried out based on a cross-sectional study in the Liangshan area, Sichuan province in Southwestern China. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used to test for the presence of SNP + 45 T > G (rs2241766) in the AdipoQ gene. RESULTS: Distributions of genotypes variants (TT/GG/TG) were not significantly different between T2D cases and controls both in Yi and Han people in China (p > 0.05). The allele frequencies (T/G) demonstrated a non-significant association with T2D, displaying OR of 1.1 (95 % CI: 0.8, 1.6) in Yi people and OR of 1.0 (95 % CI: 0.7, 1.4) in Han people. CONCLUSIONS: The SNP + 45 (rs2241766) of the AdipoQ gene is not associated with T2D neither in Yi nor in Han people in southwestern China. PMID- 22673924 TI - Therapeutic effect of metformin and vitamin E versus prescriptive diet in obese adolescents with fatty liver. AB - OBJECTIVE: The aim of the study was to determine whether metformin or vitamin E treatment for six months is effective in reducing body weight, blood pressure, and also ameliorating insulin resistance, adiponectin, and tumor necrosis factor (TNF)-alpha in obese adolescents with non-alcoholic fatty liver disease (NAFLD). METHODS: Sixty-seven obese adolescents with liver steatosis (age range, 9 - 17 years) were included in the study. The metformin group received an 850-mg dose of metformin daily and the vitamin E group received 400 U vitamin E /daily, in capsule form for 6 months, plus an individually tailored diet, exercise, and behavioral therapy. RESULTS: After 6 months later, there was a significant decline in body mass index, and fasting insulin and homeostatic model assessment (HOMA) values in all three groups. Moreover, in comparingson of changes in HOMA among the groups, the metformin- treated group showed significantly improved metabolic control and insulin sensitivity (HOMA) at the end of the study. There were no significant differences for changes of adiponectin, TNF-alpha, in all three groups after 6 months study. CONCLUSION: These data suggest that metformin treatment is more effective than dietary advice and vitamin E treatment in reducing insulin resistance, and also in ameliorating metabolic parameters such as fasting insulin and lipid levels, in obese adolescents having NAFLD. PMID- 22673925 TI - The copyist model of response emission. AB - The variety of different performances maintained by schedules of reinforcement complicates comprehensive model creation. The present account assumes the simpler goal of modeling the performances of only variable reinforcement schedules because they tend to maintain steady response rates over time. The model presented assumes that rate is determined by the mean of interresponse times (time between two responses) between successive reinforcers, averaged so that their contribution to that mean diminishes exponentially with distance from reinforcement. To respond, the model randomly selects an interresponse time from the last 300 of these mean interresponse times, the selection likelihood arranged so that the proportion of session time spent emitting each of these 300 interresponse times is the same. This interresponse time defines the mean of an exponential distribution from which one is randomly chosen for emission. The response rates obtained approximated those found on several variable schedules. Furthermore, the model reproduced three effects: (1) the variable ratio maintaining higher response rates than does the variable interval; (2) the finding for variable schedules that when the reinforcement rate varies from low to high, the response rate function has an ascending and then descending limb; and (3) matching on concurrent schedules. Because these results are due to an algorithm that reproduces reinforced interresponse times, responding to single and concurrent schedules is viewed as merely copying what was reinforced before. PMID- 22673926 TI - The effect of carboxylesterase 1 (CES1) polymorphisms on the pharmacokinetics of oseltamivir in humans. AB - PURPOSE: The aim of this study was to examine whether carboxylesterase 1 (CES1A) genetic polymorphisms affect the pharmacokinetics of oseltamivir. METHODS: Thirty healthy Japanese male and female subjects ranging in age from 20 to 36 years voluntarily participated in this study. These subjects were administered a single 75-mg dose of oseltamivir (Tamiflu(r)), and blood samples were collected predose and up to 24 h after oseltamivir administration. Oseltamivir and its active metabolite, oseltamivir carboxylate, were measured by liquid chromatography-time of flight/mass spectrometry with solid-phase extraction. The CES1A diplotypes [a combination of haplotypes A (CES1A3-CES1A1), B (CES1A2-CES1A1), C (CES1A3 CES1A1variant), and D (CES1A2-CES1A1variant)] were determined by PCR-restriction fragment length polymorphism analysis and direct sequencing. RESULTS: All subjects completed the study according to the protocol, and no clinically meaningful adverse events were attributable to the administration of oseltamivir. No significant differences in the pharmacokinetic parameters of oseltamivir and oseltamivir carboxylate were observed according to CES1A genotype. In one subject, the peak concentration and area under the concentration-time curve (AUC) of oseltamivir were approximately tenfold higher than the mean values of the other subjects. CONCLUSIONS: In our study, the known interindividual variability in oseltamivir metabolism was not explained by CES1A genetic polymorphisms, but are likely the result of other factors. While one subject was found to exhibit an approximate tenfold higher AUC than the other subjects, no abnormal behaviors were associated with the increased oseltamivir plasma concentrations. Further studies are required to reveal the cause of individual differences in CES1A metabolism and the abnormal behavioral effects of oseltamivir. PMID- 22673928 TI - Evaluation of adverse drug reactions in medical intensive care units. AB - PURPOSE: Patterns of adverse drug reactions (ADRs) in the medical intensive care unit (MICU) were analysed, and signals for detecting ADRs were developed from the analysis. METHOD: A retrospective study was conducted in MICU wards at a tertiary care teaching hospital in Seoul, Korea. The areas included one general MICU and one cancer centre MICU. Two pharmacists evaluated ADRs in terms of length of stay, causality, severity, preventability, types, related organs, and incidence. Differences in ADR perception rates between physicians and pharmacists were also evaluated. ADR cases detected through the evaluation were reviewed to develop specific alerting signals for ICU ADRs. RESULTS: The study group included 346 patients admitted to the ICU over 4 months. The overall incidence of ADRs was 32%. ICU length of stay is closely related to ADRs (p = 0.014). Most ADR cases were mild, temporary, and harmful to the patient. Twenty percent of ADRs were preventable, and 74% were type A. Of the ADRs, 70% were noted by physicians; 80% required intervention. The most commonly implicated drug was amphotericin B, and the clinical presentation was a haematologic reaction. Data on the time required for pharmacists to identify ADRs indicated that they were not slower than physicians. Six signals for early detection of the ADRs were developed. CONCLUSIONS: The overall ADR incidence in the MICU was about one-third, and the length of stay of the ADR group was longer than that of those without this experience. Automated signal generation was developed. It seemed to be a valuable tool for faster and more efficient patient management, and possibly prevention of ADRs. A future study should scientifically evaluate the clinical relevance of this tool. PMID- 22673927 TI - Recognition of adverse drug events in older hospitalized medical patients. AB - OBJECTIVE: To assess medical teams' ability to recognize adverse drug events (ADEs) in older inpatients. METHODS: The study cohort comprised 250 patients aged 65 years or older consecutively admitted to Internal Medicine wards of three hospitals in the Netherlands between April and November 2007. An independent expert team identified ADEs present upon admission or occurring during hospitalization by a structured retrospective patient chart review. For all ADEs identified, the expert team assessed causality, severity, preventability, and recognition by medical teams. RESULTS: The medical teams did not recognize 19.9 % of all ADEs present upon admission {60.4 ADEs [95 % confidence interval (CI) 51.5 70.8] per 100 hospitalizations} and 20.3 % of all ADEs occurring during the hospital stay [47.2 ADEs (95 % CI 39.4-56.5) per 100 hospitalizations]. Unrecognized ADEs were significantly more often ADEs with possible causality (p=0.014, df=1), ADEs caused by medication errors (p<0.001, df=1), and ADEs not manifesting as new symptoms (p<0.001, df=1). The medical teams did not recognize 23.2 % of mild to moderately severe ADEs and 16.5 % of severe, life-threatening, or fatal ADEs. The recognition of ADEs varied with event type. CONCLUSIONS: The recognition of ADEs by medical teams was substantial for those ADEs with evident causality and with clinically apparent and severe consequences. ADEs mimicking underlying pathologies with a lower severity went unrecognized much more often, as did those resulting only in abnormal laboratory values. Tools to improve the recognition of ADEs by medical teams should, therefore, focus on those ADEs that are more challenging to detect. PMID- 22673929 TI - Motor coordination impairment and migraine in children: a new comorbidity? AB - Migraine without aura (MoA) could be considered the most frequent form of primary headache in children, associated with many known comorbidities, but only the recent literature has begun to consider the importance of motor impairment linked to the attacks. The developmental coordination disorder (DCD) is a very common problem among children, with a prevalence ranging up to 19 %. The aim of this study was to evaluate the presence of motor coordination impairment in a population of children affected by MoA, and its role as putative risk factor for motor skills impairment. This observational study was performed in the Clinic of Child and Adolescent Neuropsychiatry of the Second University of Naples. MoA was diagnosed according to the International Classification of Headache Disorders (IHS-2) criteria. The study population consisted of 27 patients affected by MoA (16 females, 11 males) (mean age: 8.7 +/- 2.15 years) and 59 typically developing children (34 females, 25 males) (mean age: 8.0 +/- 2.1 years). The whole population underwent a clinical evaluation in order to assess the total IQ level, the visual motor integration skills, and the presence of DCD. Our results showed that MoA children had more impairments in motor coordination (p < 0.001) and visual motor integration (p < 0.001) than control group. To our knowledge, this is the first study to assess the association of poor motor coordination and MoA in children using objective measurements. These findings suggest a new perspective in the management of migraine disease in children, pinpointing that the relationship between DCD and migraine could represent a not yet understood or identified comorbidity, even if further reports are necessary, and that migraine probably could be considered not only a painful syndrome in future. PMID- 22673930 TI - A time for reappraisal of "atypical" hemolytic uremic syndrome: should all patients be treated the same? AB - Atypical hemolytic uremic syndrome (HUS) refers to the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury in the absence of Shiga toxin-producing Escherichia coli exposure or Streptococcus pneumoniae infection. Currently, approximately 50 % of the atypical cases have demonstrable mutations in complement regulatory proteins. Historically, the diagnosis of atypical HUS portends a poor prognosis with a high rate of disease recurrence, progression to end-stage renal disease, and death. However, it is now evident that atypical HUS actually encompasses a heterogeneous group of disorders, and there are reports suggesting that some cases of atypical HUS have a favorable prognosis, similar to that of diarrhea-associated disease. We present three patients with the atypical HUS phenotype who had complete renal recovery and no disease recurrence. We believe it is important to distinguish those cases of atypical HUS associated with disorders of complement regulatory proteins from other idiopathic causes of nondiarrheal HUS given the implications for prognosis and treatment. CONCLUSION: Given the heterogeneous nature and variable prognosis of atypical HUS, treatment should be carefully considered prior to the use of long-term plasma therapy and/or eculizumab. PMID- 22673931 TI - Differences in neutralizing antigenicity between laboratory and clinical isolates of HCoV-229E isolated in Japan in 2004-2008 depend on the S1 region sequence of the spike protein. AB - Human coronavirus (HCoV) is a causative agent of the common cold. Although HCoV is highly prevalent in the world, studies of the genomic and antigenic details of circulating HCoV strains have been limited. In this study, we compared four Japanese isolates with the standard HCoV-229E strain obtained from ATCC (ATCC VR740) by focusing on the spike (S) protein, a major determinant of neutralizing antigen and pathogenicity. The isolates were found to have nucleotide deletions and a number of sequence differences in the S1 region of the S protein. We compared two of the Japanese isolates with the ATCC-VR740 strain by using virus neutralizing assays consisting of infectious HCoV-229E particles and vesicular stomatitis virus (VSV)-pseudotyped virus carrying the HCoV-229E S protein. The two clinical isolates (Sendai-H/1121/04 and Niigata/01/08) did not react with antiserum to the ATCC-VR740 strain via the neutralizing test. We then constructed a pseudotype VSV-harboured chimeric S protein with the ATCC S1 and Sendai S2 regions or that with Sendai S1 and ATCC S2 regions and compared them by a neutralization test. The results revealed that the difference in the neutralizing antigenicity depends on the S1 region. This different antigenic phenotype was also confirmed by a neutralizing test with clinically isolated human sera. These results suggest that the HCoV-229E viruses prevalent in Japan are quite different from the laboratory strain ATCC-VR740 in terms of the S sequence and neutralization antigenicity, which is attributed to the difference in the S1 region. PMID- 22673932 TI - Construction of an infectious Chikungunya virus cDNA clone and stable insertion of mCherry reporter genes at two different sites. AB - Chikungunya virus (CHIKV) has caused massive epidemics in the Indian Ocean region since 2005. It belongs to the genus Alphavirus and possesses a positive-stranded RNA genome of nearly 12 kb in size. To produce genetically modified viruses for the study of various aspects of the CHIKV life cycle, a reverse genetic system is needed. We report the generation of a T7 RNA polymerase-driven infectious cDNA clone of CHIKV. Electroporation of in vitro-transcribed RNA resulted in the recovery of a recombinant virus with growth characteristics comparable to the parental strain. Using the established cDNA clone, the red fluorescent marker gene mCherry was introduced into two different sites within the CHIKV nsP3 gene. Both constructs allowed the rescue of stable fluorescent reporter viruses with growth characteristics similar to the wild-type virus. The latter reporter viruses represent valuable tools for easy follow-up of replicating CHIKV useful in several applications of CHIKV research. PMID- 22673933 TI - Organ tropism of murine coronavirus does not correlate with the expression levels of the membrane-anchored or secreted isoforms of the carcinoembryonic antigen related cell adhesion molecule 1 receptor. AB - Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is the sole known receptor of murine hepatitis virus (MHV) A59, but the available, often qualitative, data about CEACAM1 expression does not explain MHV organ tropism. Ceacam1 transcripts undergo alternative splicing resulting in multiple isoforms, including secreted CEACAM1 isoforms that can neutralize the virus. We determined the quantities of Ceacam1 transcripts encoding membrane-bound and secreted isoforms in mouse organs and a set of cell lines. In vivo, the lowest receptor mRNA levels were found in brain and muscle and these were similar to those in easily infectable cultured cells. While the quantities of the receptor transcripts varied between mouse organs, their abundance did not correlate with susceptibility to MHV infection. The proportion of transcripts encoding secreted isoforms also could not explain the selection of sites for virus replication, as it was constant in all organs. Our data suggest that neither of the two CEACAM1 isoforms defines MHV organ tropism. PMID- 22673934 TI - Retrovirus-induced lymphomagenesis: a correlation between disease pathogenesis and flow cytometric analysis. AB - Perinatal infection with a temperature-sensitive mutant (ts-1) of Moloney murine leukemia virus (MoMuLV) results in massive splenomegaly and thymomegaly in mice and development of lymphoma in >55 % of infected pups. Previous flow cytometry studies showed a decrease in CD4(+) cells in perinatally infected pups, but cell population changes in infected animals with lymphoma compared with infected animals without lymphoma has not yet been reported. In the current study, BALB/c mice were infected with ts-1 through breast milk transmission and observed until development of clinical signs and symptoms of lymphoma and/or symptomatic ts-1 infection. Flow cytometry studies were performed on blood, spleen and thymus samples and correlated with gross morphology and histological changes, resulting from the development of lymphoma. Infected animals with lymphoma had significant decreases in CD4(+) and CD8(+) cell counts in blood and spleen compared with controls. The spleens of infected animals without lymphoma showed a decrease in CD4(+) and CD8(+) cell counts, but this was not significant compared with controls. In the thymus, CD4(+) and CD8(+) cell counts also decreased, but this was not significant in infected animals with and without lymphoma compared with controls. Markers of myeloid cell dysfunction increased in the thymus of animals with infection with and without lymphoma compared with controls. Thus, immunosuppression and CD4(+)/CD8(+) cell decreases in the spleen and thymus are associated with malignant transformation and development of lymphoma in this animal model. PMID- 22673935 TI - Calcium handling and ventricular tachyarrhythmias. AB - Pharmacologic modification of cellular calcium handling recently moved into focus as an alternative for prevention and treatment of ventricular tachyarrhythmias. Calcium overload and spontaneous calcium release from the sarcoplasmatic reticulum are regarded as possible initiations of early and delayed afterdepolarization thereby triggering ventricular arrhythmias. In chronic heart failure, calcium overload is more likely to occur compared with healthy hearts, which is one explantation for the increased vulnerability in this condition. L type calcium channel, sodium-calcium-exchanger (NCX), and ryanodine receptor are crucial for calcium homeostasis and therefore represent potential targets for antiarrhythmic drug therapy. Experimental studies have proven beneficial effects for all these three mechanisms in prevention and suppression of tachyarrhythmias. However, clinical data is mainly available for the L-type calcium channel inhibitor verapamil. Therefore, it is still a long way to clinical employment of drugs modifying cellular calcium handling for antiarrhythmic therapy. PMID- 22673937 TI - Cytokine and satellite cell responses to muscle damage: interpretation and possible confounding factors in human studies. AB - It is plausible that multiple muscle biopsies following a muscle damaging intervention can exacerbate the inflammatory and subsequent satellite cell responses. To elucidate confounding effects of muscle biopsy procedure on satellite cell number, indirect markers of damage and the inflammatory response following acute downhill running (DHR) were investigated. 10 healthy male participant were divided into a non-exercising control (n = 4) and DHR (12 * 5min bouts, 10 % decline at 85 % VO(2)max) (n = 6) group. Blood samples were taken pre, post and every 24 h for 9 days. Serum was analysed for creatine kinase (CK), myoglobin (Mb), lactate dehydrogenase (LDH), TNF-alpha, IL-6 and IL-10. Muscle biopsies taken on days 1 and 2 post intervention from opposing legs were analysed for Pax7(+) satellite cells. In the DHR group, Mb (536 +/- 277 ng mL(-1)), IL-6 (12.6 +/- 4.7 pg mL(-1)) and IL-10 (27.3 +/- 11.5 pg mL(-1)) peaked immediately post DHR, while CK (2651 +/- 1911 U L(-1)), LDH (202 +/- 47 U L(-1)) and TNF alpha (25.1 +/- 8.7 pg mL(-1)) peaked on day 1. A 30 % increase in Pax7(+) satellite cells on day 1 in the DHR group was no longer apparent on day 2. H&E staining show evidence of phagocytosis in the DHR group. No significant changes over time were observed in the control group for any of the variables measured. Events observed in the DHR group were as a result of the intervention protocol and subsequent muscle damage. The relationship between SC proliferation and pro inflammatory cytokine release appears to be complex since the IL-6/IL-10 response time differs significantly from the TNF-alpha response. PMID- 22673936 TI - Current evidence that exercise can increase the number of adult stem cells. AB - The number of adult stem cells (ASCs) is very small, limiting the regenerative potential of tissues. One of the most studied ASCs in humans is the satellite cell (SC), which proliferates and increases pool size under exercise stress and muscle damage. This review examines the growth factor response to specific types of exercise to show the potential of exercise to stimulate not only SC self renewal, but also other ASCs. We postulate that the same factors that stimulate a high proliferation of SCs in skeletal muscle after physical exercise should also stimulate the proliferation of ASCs in the tissue in which they reside, such as heart, bone, liver and etc. Regular exercise should be promoted, not only for disease prevention, but to maintain a high ASCs reserve and progenitor cell potential for rapid activation in response to future stressors and damage. PMID- 22673938 TI - Determination of ofloxacin in tear by HPLC-ESI-MS/MS method: comparison of ophthalmic drug release between a new mucoadhesive chitosan films and a conventional eye drop formulation in rabbit model. AB - Ofloxacin, second-generation fluoroquinolone derivative, is one of the most commonly used to treat and prevent superficial ocular infection in animals and human beings. However, poor bioavailability, rapid elimination, and non compliance by patients are several problems associated with ocular route. Ophthalmic controlled drug delivery offers the potential to enhance the efficacy of treatment for pathological conditions, while reducing the side effects and the toxicity associated with frequent applications. Specific analytical methods to determine drugs in eye are needed to analyze and compare the new controlled release ocular devices with those conventional eye drops. The topical eye administration of ophthalmic drugs induces lachrymation, and the tear promotes a drug wash out. Quantify drugs in tear is a good tool to study their kinetic comportment in the eye. A liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) method for quantitation of ofloxacin in rabbits' tears was developed and validated. The tear was collected with tear strips, extracted by a liquid extraction procedure and then separated on an ACE C(18) column with a mobile phase composed of 0.15% aqueous formic acid and methanol (60:40, v/v). Calibration curve was constructed over the range of 10 5000 ng/mL for ofloxacin. The mean R.S.D. values for the intra-run and inter-run precision were 5.15% and 4.35%, respectively. The mean accuracy value was 100.16%. The validated method was successfully applied to determine the ofloxacin concentration in tears of rabbits treated with a mucoadhesive chitosan films and a conventional eye drop formulation. PMID- 22673941 TI - Role of Tris on the colorimetric recognition of anions with melamine-modified gold nanoparticle probe and the visual detection of sulfite and hypochlorite. AB - Colorimetric recognition and sensing of sulfite by melamine-modified gold nanoparticle is reported, using Tris-HCl as the operating buffer. Furthermore, indirect determination of hypochlorite is accomplished by its oxidation of sulfite. PMID- 22673940 TI - Bioactive alkaloid extracts from Narcissus broussonetii: mass spectral studies. AB - Plants of the Amaryllidaceae family are a well-known source of tetrahydroisoquinoline alkaloids with a wide range of biological activities, including antiviral, antitumoral, antiparasitic, psychopharmacological, and acetylcholinesterase inhibitory, among others. Recent advances in the use of GC or LC coupled to MS have allowed a chemically guided isolation of uncommon and bioactive alkaloids. In the present work, analytical methods were applied to study the alkaloid profile of Narcissus broussonetii, a plant endemic to North Africa. Using the GC-MS technique and an in-home mass fragmentation database, twenty-three alkaloids were identified, including the very rare dinitrogenous alkaloids obliquine, plicamine, and secoplicamine. Applying LC-ESI-LTQ-Orbitrap MS, fragmentation profiles were found to be similar for obliquine and plicamine but different for secoplicamine. Pretazettine, a potent cytotoxic alkaloid, was also isolated from N. broussonetii, although its identification by GC-MS was only possible after a BSTFA-derivatization. The silylated crude methanolic extract only showed the presence of pretazettine-TMS, confirming that tazettine was formed after the alkaloid extraction. The same observation was made in Narcissus cultivars in which tazettine had been detected as the major alkaloid. As part of an ongoing project on MS of Amaryllidaceae alkaloids, the silylated tazettine and pretazettine were studied by GC-MS/MS, and found to differ in their fragmentation routes. Finally, the EtOAc extract of N. broussonetii showed notable in vitro activity against Trypanosoma cruzi, with an IC(50) value of 1.77 MUg/ml. PMID- 22673943 TI - N-acylation: an effective method for reducing the LUMO energy levels of conjugated polymers containing five-membered lactam units. AB - N-acylation was studied as a method for reducing the LUMO energy levels of benzodipyrrolidone-based polymers. The N-acylated polymers showed reduced LUMO levels and improved reversibility of reductive doping compared with N-alkylated polymers. This method may also apply in other conjugated polymers with lactam repeating units. PMID- 22673944 TI - Island shapes and aggregation steered by the geometry of the substrate lattice. AB - We find that island shapes and aggregation in diindenoperylene deposited on Au(100), Au(110), and Au(111) single crystals are steered by the anisotropy due to the lattice geometry of the substrate. This phenomenon may be exploited as a tool for molecular patterning of surfaces. PMID- 22673946 TI - [Clinical experience of treatment with onabotulinumtoxin A in patients with refractory migraine]. AB - AIM: To analyse our experience in the treatment of refractory chronic migraine, episodic frequent refractory migraine (>=10 days/month), with onabotulinumtoxin A (OnabotA). PATIENTS AND METHODS: Retrospective analysis of patients with refractory migraine who underwent, at least two sessions of OnabotA pericranial injections following the PREEMPT protocol between 2008 and 2012. The efficacy of OnabotA was evaluated comparing the basal situation with 12-16 weeks after the second session. We analysed the subjective improvement of the patients, number of days with headache, preventive and abortive drugs consumption, and adverse effects. RESULTS: Forty-one patients (37 women, 4 male) were identified. 65.8% patients experienced subjective improvement after OnabotA treatment. 36.58% responded (reduction of > 50% in headache days). Differences between days with headache before the first session (24.5 +/- 7.3), and 12-16 weeks after the second session (17.4 +/- 11.6), as well as the differences between the number of abortive drugs taken before the first session (26.8 +/- 23.1) and 12-16 weeks after the second session (16.7 +/- 19.3), were statistically significant (p < 0.001). Subgroups analysis showed that all differences were significant, except for the reduction of the number of days with headache in patients with episodic frequent refractory migraine. CONCLUSION: Our work shows that treatment with OnabotA is safe and useful in patients with episodic and chronic refractory migraine, including those patients with medication overuse headache. PMID- 22673945 TI - Identification of polymorphisms in ultraconserved elements associated with clinical outcomes in locally advanced colorectal adenocarcinoma. AB - BACKGROUND: Ultraconserved elements (UCEs) are noncoding genomic sequences that completely identical among human, mouse, and rat species and harbor critical biologic functions. The authors hypothesized that single nucleotide polymorphisms (SNPs) within UCEs are associated with clinical outcomes in patients with colorectal cancer (CRC). METHODS: Forty-eight SNPs within UCEs were genotyped in 662 patients with stage I through III CRC. The associations between genotypes and recurrence and survival were analyzed in patients with stage II or III CRC who received fluoropyrimidine-based adjuvant chemotherapy using a training and validation design. The training set included 115 patients with stage II disease and 170 patients with stage III disease, and the validation set included 88 patients with stage II disease and 112 patients with stage III disease. RESULTS: Eight SNPs were associated with clinical outcomes stratified by disease stage. In particular, for patients with stage II CRC who had at least 1 variant allele of reference SNP sequence 7849 (rs7849), a consistent association with increased recurrence risk was observed in the training set (hazard ratio [HR], 2.39; 95% confidence interval [CI], 1.04-5.52), in the replication set (HR, 3.70; 95% CI, 1.42-9.64), and in a meta-analysis (HR, 2.89; 95% CI, 1.54-5.41). Several other SNPs were significant in the training set but not in the validation set. These included rs2421099, rs16983007, and rs10211390 for recurrence and rs6590611 for survival in patients with stage II disease; and SNPs rs6124509 and rs11195893 for recurrence in patients with stage III disease. In addition, a significant cumulative effect was observed of multiple risk genotypes and potential gene-gene interactions on recurrence risk. CONCLUSIONS: To the authors' knowledge, this is the first study to evaluate the association between SNPs within UCEs and clinical outcome in patients with CRC. The results suggested that SNPs within UCEs may be valuable prognostic biomarkers for patients with locally advanced CRC who receive 5-fluorouracil-based chemotherapy. PMID- 22673947 TI - [Neurotoxicity due to methotrexate in paediatric patients. Description of the clinical symptoms and neuroimaging findings]. AB - INTRODUCTION. High-dose methotrexate (MTX) has showed to increase the surveillance in children with acute lymphoblastic leukemia and other neoplasms. However, MTX may induce significant neurotoxicity. AIM. To evaluate, in our population of patients who have been treated with MTX, the incidence of neurotoxicity and to describe its main clinical and radiological characteristics. PATIENTS AND METHODS. We retrospectively review the patients who received treatment with systemic high-dose MTX and/or intrathecal MTX between 1994 and 2010. The children who presented clinical o radiological signs of neurotoxicity were reviewed. RESULTS. We identified 284 patients who received high-dose intravenous and/or intrathecal MTX. 9 patients presented neurotoxicity. The median age at diagnosis was 6 years; 6 patients were male. The diagnosis included: 6 acute lymphoblastic leukemia, 2 medulloblastoma and 1 lymphoma. 66% patients presented focal neurological dysfunction, 3 had non-specific symptoms. In 5 patients the symptomatology started the first 14 days after the MTX administration. 8 patients had complete clinical resolution, but only one presented neurological long term effects. All the patients except one showed signs of acute leukoencephalopathy in the brain MR study. These alterations resolved one year later in 3 patients; in the other patients the MR alterations persisted. The neurotoxicity management was corticosteroid, folinic acid, aminophylline and dextromethorphan. CONCLUSION. The MTX neurotoxicity it can present as acute or chronic. It has a wide clinical spectrum, ranging from sub clinical manifestations with complete recovery to a chronic and progressive encephalopathy. PMID- 22673948 TI - [Incidence of hospitalization for traumatic brain injury in children and adolescents (Valencia Community, Spain, 2002-2009)]. AB - INTRODUCTION. Traumatic brain injuries (TBI) are a major cause of morbidity and mortality in children and adolescents but there are hardly any studies on the incidence and temporal evolution. AIM. To describe recent trends (2002-2009) in the incidence of hospitalization for TBI in children and adolescents in the region of Valencia. PATIENTS AND METHODS. Emergency admissions were identified in hospitals in the Valencian Health Agency from patients aged 0-19 years with a diagnosis of TBI (codes of the International Classification of Diseases 800, 801, 803, 804 and 850 to 854) during 2002 to 2009. The severity was classified using the fifth digit of these codes and the crude and standardized rates per 100,000 children were estimated stratified by age, sex and severity. RESULTS. From 2002 to 2009 a total of 5,504 TBI in children up to age of 19 years were hospitalized (mild: 92.9%; moderate to severe: 7.1%). In-hospital mortality was 0.6% for mild TBI and 15.7% for moderate-severe. Crude rates of mild head injury per 100,000 children fell from 85.9 to 55.4 in 2002-2009 (boys: 114.1 to 68.3, girls: 56.1 to 41.8), especially in the 15-19 years. For moderate-severe TBI, rates decreased from 5.73 to 2.78 per 100,000 in 2002-2009 (boys: 8.69 to 3.67; girls: 2.59 to 1.84). CONCLUSIONS. The incidence of pediatric TBI in the Valencia region has decreased significantly in the period 2002-2009, but their medical, legal, societal and family consequences still represents a substantial burden. PMID- 22673949 TI - [Tolosa-Hunt syndrome following traumatic eye injury]. AB - INTRODUCTION: Tolosa-Hunt syndrome (THS) is an idiopathic condition involving unilateral eye pain with involvement of oculomotor nerves which responds well to treatment with steroids. It is produced by idiopathic granulomatous inflammation of the cavernous sinus or the orbital apex. CASE REPORT: A 37-year-old male who was admitted to hospital due to a six-week history of blurred vision and pain in the left eye, which was later accompanied by full ipsilateral ophthalmoplegia. Some days prior to the onset of the clinical features, he suffered an accident which resulted in traumatic injury to the left eye. An examination showed data pointing to optic neuropathy in the left eye with complete extrinsic ocular motor palsy. Results of general analyses and lumbar puncture were normal. Magnetic resonance imaging (MRI) of the head revealed a thickening of the wall of the left cavernous sinus and of the ipsilateral orbital apex, which enhanced with gadolinium. Evoked potential studies showed axonal and demyelinating optic neuropathy on the left-hand side. Suspecting this to be a case of THS, treatment was established with high doses of corticoids, which brought about an improvement in the pain and eye movement but not in the blurred vision. A MRI control scan showed a clear improvement in comparison to the one carried out initially. CONCLUSIONS: In cases of painful ophthalmoplegia, the professional should suspect the existence of THS. If the apex of the orbit is affected through the superior orbital fissure, the optic nerve may be damaged. Traumatic injury can be one of the situations that trigger THS. PMID- 22673950 TI - Review of the novelties presented at the 27th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (II). AB - The new insights presented at the 5th Joint Triennial Congress of the European and Americas Committees on Treatment and Research in Multiple Sclerosis (ECTRIMS and ACTRIMS) held in Amsterdam, the Netherlands, 19-22 October 2011, have been summarized at the fourth edition of Post-ECTRIMS meeting held in Madrid in November 2011. Regional grey-matter atrophy is more sensitive to cognitive impairment than global grey-matter atrophy measures. In patients with clinically isolated syndrome cognitive impairment does not predict conversion to multiple sclerosis (MS) after 5-years of follow-up. Focusing on central nervous system plasticity and functional reorganization in MS, an early intervention can improve clinical aspects and enhances brain plasticity. Preservation of a potential for plasticity provides a rationale for rehabilitation interventions even in later stages of disease. Therapeutical strategies have focused on stem cell-mediated remyelination and immunomodulation functions, on cellular infiltration into the brain, and on new ways for immuno-modulation for the development of future therapies in MS. Encouraging findings from clinical trials with current and emerging disease-modifying therapy being developed was also a key theme at this edition. Positive results have been reported for rituximab, ocrelizumab, ofatumumab, daclizumab, alemtuzumab, teriflunomide, BG-12, and laquinimod, including a favorable safety profile. Since armamentarium for the treatment of MS is fast increasing, concerns exist about the risk of severe adverse events with their use. This aspect reinforces the importance of disease registries as a proactive tool for monitoring drug safety in the post-approval setting. PMID- 22673951 TI - [Mental disorders and neuropsychological impairment related to chronic use of cannabis]. AB - INTRODUCTION. Cannabis is an illegal drug in wide use nowadays, mainly for recreational purposes. It is considered one of the less harmful drugs, partly due to the large amount of information to which most people have access. However, the scientific literature could reveal important clues to the contrary. AIM. To gather and resume updated scientific data from different fields (clinical psychology, neurobiology, neuroimaging...) about the effects and consequences of the chronic use of cannabis. DEVELOPMENT. Evidence concerning the mental disorders and neuropsychological impairment associated the most to the chronic use is presented along with comments on the possible underlying neurobiological mechanisms, and the most important risk factors are also described. CONCLUSIONS. The evidence indicates that frequent and prolonged use of cannabis can be detrimental to mental health. A high risk of psychotic symptoms in predisposed individuals, higher for frequent users, is described, while the findings on symptoms of depression and anxiety are less consistent. On the cognitive behavioral level, the functions most affected seem to be the attentional and executive ones. These data can be valuable both to guide further research and for updating the sensibilization and prevention programs on cannabis abuse. PMID- 22673953 TI - [Symptomatic hypothalamic osteolipoma]. PMID- 22673954 TI - [Atypical presentation of esthesioneuroblastoma]. PMID- 22673955 TI - [Post-traumatic syringomyelia or caused by tonsillar descent?]. PMID- 22673958 TI - Short of transformation: American ADN students' thoughts, feelings, and experiences of studying abroad in a low-income country. AB - ADN students are a large yet distinct subgroup of nursing students who require research and understanding. The purpose of this study was to describe the thoughts, feelings, and experiences of American associate degree nursing (ADN) students who participated in a short study abroad course in a low-income country. A qualitative, narrative method was used. Three categories emerged from the analysis. Participants revealed thoughts of "constant comparisons", feelings of an "emotional journey", and they experienced "learning". Participants did not demonstrate perspective transformation as defined by Mezirow as participants signified no intent for social action. Several potential blocks to perspective transformation were identified: egocentrism/emotional disconnect, perceived powerlessness/being overwhelmed, and a vacation mindset. The findings provide insight into the student experience of studying abroad. Transformative learning is not a guaranteed result. Nurse educators must consider strategies to foster transformation including discussing global systemic oppressors, international relations, coping, connecting, and social action. PMID- 22673957 TI - Tumor-induced myeloid-derived suppressor cell function is independent of IFN gamma and IL-4Ralpha. AB - Myeloid-derived suppressor cells (MDSCs) are present in most cancer patients and experimental animals where they exert a profound immune suppression and are a significant obstacle to immunotherapy. IFN-gamma and IL-4 receptor alpha (IL 4Ralpha) have been implicated as essential molecules for MDSC development and immunosuppressive function. If IFN-gamma and IL-4Ralpha are critical regulators of MDSCs, then they are potential targets for preventing MDSC accumulation or inhibiting MDSC function. Because data supporting a role for IFN-gamma and IL 4Ralpha are not definitive, we have examined MDSCs induced in IFN-gamma deficient, IFN-gammaR-deficient, and IL-4Ralpha-deficient mice carrying three C57BL/6-derived (B16 melanoma, MC38 colon carcinoma, and 3LL lung adenocarcinoma), and three BALB/c-derived (4T1 and TS/A mammary carcinomas, and CT26 colon carcinoma) tumors. We report that although MDSCs express functional IFN-gammaR and IL-4Ralpha, and have the potential to signal through the STAT1 and STAT6 pathways, respectively, neither IFN-gamma nor IL-4Ralpha impacts the phenotype, accumulation, or T-cell suppressive potency of MDSCs, although IFN gamma and IL-4Ralpha modestly alter MDSC-macrophage IL-10 crosstalk. Therefore, neither IFN-gamma nor IL-4Ralpha is a key regulator of MDSCs and targeting these molecules is unlikely to significantly alter MDSC accumulation or function. PMID- 22673959 TI - A phenomenological perspective on preceptorship in the intergenerational context. AB - Pairing a student with an experienced nurse through preceptorship is an approach to teaching/learning that promotes critical thinking, cultivates practical wisdom, and facilitates competence. Frequently, nursing students are of a different generation than their assigned preceptors and differences in worldviews and expectations can impact upon the success of preceptorship. A phenomenological study, guided by van Manen's approach to human science research, was conducted to explore preceptorship within this intergenerational context. Data were generated using unstructured interviews with a purposive sample of seven preceptors and seven students recruited from an undergraduate nursing program. The findings reveal three main themes: being affirmed, being challenged, and being on a pedagogical journey. The findings of this study have the potential to enhance generational understanding in the pedagogical context and foster a teaching/learning culture in the clinical practice setting inclusive of divergent generational expectations. PMID- 22673960 TI - End-of-life care and the use of simulation in a baccalaureate nursing program. AB - End-of-life care is not traditionally associated with high technology, yet simulations have the potential to transform palliative care nursing education. This university incorporates a high-fidelity simulation scenario to teach undergraduate students this content. Since 76% of dying patients are under nursing care at the time of death, nurses need to be prepared to care for these patients. Simulated experiences have been shown to be particularly beneficial when dealing with emotionally charged issues like end-of-life care. This modality allows students to practice the assessment of the physiological changes taking place in the dying patient and the necessary patient care decisions. This article describes a pilot study evaluating undergraduate nursing students' knowledge and self-efficacy in caring for patients at the end-of-life via a simulation involving a terminally ill patient. The results show a statistically significant improvement in students' knowledge on physiological changes and self-efficacy in providing care. PMID- 22673961 TI - Student satisfaction and self report of CPR competency: HeartCode BLS courses, instructor-led CPR courses, and monthly voice advisory manikin practice for CPR skill maintenance. AB - This study evaluated the effects of brief monthly refresher training on CPR skill retention, confidence, and satisfaction with CPR skill level of 606 nursing students from ten different US schools. Students were randomized to course type, HeartCodeTM Basic Life Support (BLS) or an instructor-led (IL) course, and then randomized to a practice group, six minutes of monthly practice or no further practice. End-of-study survey results were compiled and reported as percentages. Short answer data were grouped by category for reporting. Fewer HeartCodeTM BLS students were satisfied with their CPR training compared to the IL students. Students who practiced CPR monthly were more confident than students who did not practice. Monthly practice improved CPR confidence, but initial course type did not. Students were most satisfied when they participated in the IL courses and frequent practice of CPR skills. PMID- 22673962 TI - Regulation of insulin-like growth factors and their binding proteins by thyroid stimulating hormone in human osteoblast-like (SaOS2) cells. AB - Thyroid stimulating hormone (TSH) is shown to have definite anabolic effects on skeletal metabolism. Previous studies have demonstrated that Insulin-like growth factors (IGF-I and IGF-II) and their six high affinity binding proteins (IGFBPs 1 6) regulate proliferation and differentiation of bone-forming osteoblasts. The current study was intended to determine whether the anabolic effects of TSH on human osteoblastic (SaOS2) cells are mediated through insulin-like growth factor system components. TSH given at 0.01 ng to 10 ng/ml dose levels for 24 and 48 h significantly increased human osteoblastic (SaOS2) cell proliferation and alkaline phosphatase activity, the differentiation marker. TSH significantly increased IGFs (IGF-I and IGF-II) mRNA expression after 6 and 24 h and their protein levels after 24 and 48 h of treatment, respectively. Unlike the IGFs, the IGFBPs responded differently to TSH treatment. Though there were some inconsistencies in the regulation of stimulatory IGF binding protein-3 and -5 by TSH treatment, there was an overall increase at the mRNA abundance and protein levels. Again, the inconsistency persisted at the regulation of the inhibitory IGFBPs 2, 4, and 6 especially at the level of mRNA expression due to TSH treatment, there is an overall decrease in the levels of IGFBP-2, 4, and 6 in the conditioned media (CM) of SaOS2 cell cultures. The IGFBP proteases which control the availability of IGFs are also regulated by hormones. Pregnancy-Associated Plasma Protein-A (PAPP-A) is responsible for the proteolysis of IGFBP-4. TSH treatment significantly unregulated the expression of PAPP-A both at mRNA and protein levels. In conclusion, TSH promotes human osteoblastic (SaOS2) cell proliferation and differentiation by upregulating IGFs and their stimulatory IGF binding proteins and down regulating the inhibitory IGF binding proteins. PMID- 22673964 TI - A case of sino-orbital infection caused by the Schizophyllum commune. AB - Schizophyllum commune, a basidiomycetous fungus, is a rare cause of mycotic disease in humans. We describe the first case of sino-orbital infection caused by S. commune in an immunocompetent woman who presented with maxillary sinusitis and inferior orbital tumor. Identification of the organism was confirmed by rRNA sequencing. PMID- 22673963 TI - Genome-wide association analysis of circulating vitamin D levels in children with asthma. AB - Vitamin D deficiency is becoming more apparent in many populations. Genetic factors may play a role in the maintenance of vitamin D levels. The objective of this study was to perform a genome-wide analysis (GWAS) of vitamin D levels, including replication of prior GWAS results. We measured 25-hydroxyvitamin D (25(OH)D) levels in serum collected at the time of enrollment and at year 4 in 572 Caucasian children with asthma, who were part of a multi-center clinical trial, the Childhood Asthma Management Program. Replication was performed in a second cohort of 592 asthmatics from Costa Rica and a third cohort of 516 Puerto Rican asthmatics. In addition, we attempted replication of three SNPs that were previously identified in a large GWAS of Caucasian individuals. The setting included data from a clinical trial of childhood asthmatics and two cohorts of asthmatics recruited for genetic studies of asthma. The main outcome measure was circulating 25(OH)D levels. The 25(OH)D levels at the two time-points were only modestly correlated with each other (intraclass correlation coefficient = 0.33) in the CAMP population. We identified SNPs that were nominally associated with 25(OH)D levels at two time-points in CAMP, and replicated four SNPs in the Costa Rican cohort: rs11002969, rs163221, rs1678849, and rs4864976. However, these SNPs were not significantly associated with 25(OH)D levels in a third population of Puerto Rican asthmatics. We were able to replicate the SNP with the strongest effect, previously reported in a large GWAS: rs2282679 (GC), and we were able to replicate another SNP, rs10741657 (CYP2R1), to a lesser degree. We were able to replicate two of three prior significant findings in a GWAS of 25(OH)D levels. Other SNPs may be additionally associated with 25(OH)D levels in certain populations. PMID- 22673965 TI - A rare case of Neisseria bacilliformis native valve endocarditis. AB - Neisseria bacilliformis has most often been associated with infections of the oral cavity and the respiratory tract. We report a case of N. bacilliformis mitral valve endocarditis in a previously healthy adult which required valve replacement, thus confirming the opportunistic nature and pathogenic potential of this novel organism. PMID- 22673966 TI - Clinical outcomes and resource use for infants with hypoplastic left heart syndrome during bidirectional Glenn: summary from the Joint Council for Congenital Heart Disease National Pediatric Cardiology Quality Improvement Collaborative registry. AB - The National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC) registry captures information on interstage management of infants with hypoplastic left heart syndrome (HLHS). The purpose of this study was to identify interstage risk factors for increased resource use and adverse outcomes during bidirectional Glenn (BDG) hospitalization. All infants in the NPC-QIC registry (31 United States hospitals) undergoing BDG surgery were included (December 2009 to August 2010). Patient demographics, interstage variables, operative procedures, and complications were recorded. Days of hospitalization, ventilation, inotrope use, and complications were surrogates of resource use. Logistic regression analysis determined the associations between predictor variables and resource use. Of 162 infants, 105 (65 %) were males. At BDG, the median age was 155 days (range 78-128), mean weight-for-age z-score was -1.6 +/- 1.1, mean length-for-age z-score was -1.5 +/- 1.7, and mean preoperative oxygen saturation was 78 % +/- 7 %. Caloric recommendations were met in 60 % of patients, and 85 % of patients participated in a home-surveillance program. Median days of intubation, inotrope use, and hospitalization were 1, 2, and 7, respectively. There were 4 post-BDG deaths and 55 complications. In multivariate analysis, lower weight-for-age z-score, female sex, and aortic atresia with mitral stenosis were associated with a higher risk of BDG complications. Meeting caloric recommendations before BDG was associated with fewer hospitalization days. Lower weight-for-age z-score was an independent and potentially modifiable risk factor for BDG complications. HLHS infants who met caloric recommendations before BDG had a lower duration of hospitalization at BDG. These data justify targeting nutrition in interstage strategies to improve outcomes and decrease costs for patients with HLHS. PMID- 22673967 TI - Renal dysfunction is common among adults after palliation for previous tetralogy of Fallot. AB - Long-term survival after tetralogy of Fallot (TOF) repair is excellent. However, little is published regarding late noncardiac complications. This study aimed to determine the prevalence and risk factors for renal dysfunction among adults after TOF repair. For this study, 56 adult patients with complete repair of TOF were identified, and their charts were retrospectively reviewed. An estimated glomerular filtration rate (eGFR) for each patient was calculated using the Modification of Diet in Renal Disease formula (MDRD). Using each patient's eGFR, he or she was classified into stages based on the National Kidney Foundation chronic kidney disease (CKD) staging. Clinical parameters were compared among patients with and those without renal dysfunction to identify risk factors for renal impairment. The median estimated eGFR rate for the cohort was 78 ml/min/1.73 m(2). Based on the National Kidney Foundation CKD staging system, 54 % of the patients had at least stage 2 chronic renal disease. The risk factors identified were hypertension (p < 0.01), type 2 diabetes mellitus (p < 0.05), longer follow-up evaluation (p < 0.005), older age at complete repair (p < 0.05), and use of daily diuretics (p < 0.05). After repair of TOF, renal dysfunction is common at late follow-up evaluation. The study findings show the importance of routine assessment of renal function and the need to limit or avoid future episodes of acute kidney injury in this at-risk population. PMID- 22673971 TI - Emerging implications of nonmammalian cytosine deaminases on cancer therapeutics. AB - Nonmammalian cytosine deaminases (CDs) have been investigated for last 30 years in the context of cancer therapy. The therapeutic effect of CD is based on its ability to catalyze the conversion of nontoxic prodrug 5-fluorocytosine (5FC) into the anticancer drug 5-fluorouracil (5FU) by deamination of the number 4 carbon of 5FC. This deamination property of CD has been explored to develop innovative therapeutic approach for treatment of cancer. A general overview is needed for the identification of efficient cytosine deaminases for potential use in cancer therapy. In this review, we have discussed about nonmammalian CDs for a variety of prodrug gene/enzyme therapy applications with several recent examples. Finally, we have provided a prospective on the future aspects of CDs and their applications in cancer therapy. PMID- 22673969 TI - Do coping styles mediate the relationship between substance use and educational attainment and antiretroviral adherence? AB - There is a substantial body of literature that demonstrates that substance use and lower educational attainment are associated with poorer antiretroviral (ART) adherence, however, the nature of these relationships are not well understood. The purpose of this study was to explore whether coping styles mediate the relationship between substance use and educational attainment and ART adherence in order to better understand how these variables relate to adherence. The sample consisted of 192 HIV-positive patients (mean age = 41 years; 75.5 % male, 46.9 % heterosexual; 52.6 % with a high school/GED education or less) who were on ART. Path analysis revealed that active and avoidant coping significantly mediated the relationship between drug use and ART adherence. No form of coping was found to mediate the relationship between either binge drinking or educational attainment and adherence. Findings suggest that a focus on coping skills should be included in any multimodal intervention to increase ART adherence among HIV-positive drug using patients. PMID- 22673972 TI - Survival and transplantation outcomes of children less than 2 years of age with end-stage renal disease. AB - BACKGROUND: Young children with end-stage renal disease (ESRD) requiring renal replacement therapy (RRT) have traditionally experienced high rates of morbidity and mortality; however, detailed long-term follow-up data is limited. METHODS: Using a population-based retrospective cohort with data from a national organ failure registry and administrative data from Canada's universal health care system, we analysed the outcomes of 87 children starting RRT (before age 2 years) and followed them until death or date of last contact [median follow-up 4.7 years, interquartile range (IQR) 1.4-9.8). We assessed secular trends in survival and the influence of: (1) age at start of RRT and (2) etiology of ESRD with survival and time to transplantation. RESULTS: Patients were mostly male (69.0 %) with ESRD predominantly due to renal malformations (54.0 %). Peritoneal dialysis was the most common initial RRT (83.9 %). Fifty-seven (65.5 %) children received a renal transplant (median age at first transplant: 2.7 years, IQR 2.0-3.3). During 490 patient-years of follow-up, there were 23 (26.4 %) deaths, of which 22 occurred in patients who had not received a transplant. Mortality was greater for patients commencing dialysis between 1992 and 1999 and among the youngest children starting RRT (0-3 months). Children with ESRD secondary to renal malformations had better survival than those with ESRD due to other causes. Among the transplanted patients, all but one survived to the end of the observation period. CONCLUSION: Children who start RRT before 3 months of age have a high risk of mortality. Among our paediatric patient cohort, mortality rates were much lower among children who had received a renal transplant. PMID- 22673974 TI - 30th Liverpool course-is this a record? Comprehensive review on mobile phone technologies finds no solid evidence of health effects. PMID- 22673975 TI - Beyond cost considerations. PMID- 22673968 TI - Molecular and cellular mechanisms of skeletal muscle atrophy: an update. AB - Skeletal muscle atrophy is defined as a decrease in muscle mass and it occurs when protein degradation exceeds protein synthesis. Potential triggers of muscle wasting are long-term immobilization, malnutrition, severe burns, aging as well as various serious and often chronic diseases, such as chronic heart failure, obstructive lung disease, renal failure, AIDS, sepsis, immune disorders, cancer, and dystrophies. Interestingly, a cooperation between several pathophysiological factors, including inappropriately adapted anabolic (e.g., growth hormone, insulin-like growth factor 1) and catabolic proteins (e.g., tumor necrosis factor alpha, myostatin), may tip the balance towards muscle-specific protein degradation through activation of the proteasomal and autophagic systems or the apoptotic pathway. Based on the current literature, we present an overview of the molecular and cellular mechanisms that contribute to muscle wasting. We also focus on the multifacetted therapeutic approach that is currently employed to prevent the development of muscle wasting and to counteract its progression. This approach includes adequate nutritional support, implementation of exercise training, and possible pharmacological compounds. PMID- 22673973 TI - Role of 18F-FDG PET/CT in the prediction of gastric cancer recurrence after curative surgical resection. AB - PURPOSE: The study evaluated the role of preoperative (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in the prediction of recurrent gastric cancer after curative surgical resection. METHODS: A total of 271 patients with gastric cancer who underwent (18)F-FDG PET/CT and subsequent curative surgical resection were enrolled. All patients underwent follow-up for cancer recurrence with a mean duration of 24 +/- 12 months. (18)F-FDG PET/CT images were visually assessed and, in patients with positive (18)F-FDG cancer uptake, the maximum standardized uptake value (SUV(max)) of cancer lesions was measured. (18)F-FDG PET/CT findings were tested as prognostic factors for cancer recurrence and compared with conventional prognostic factors. Furthermore, (18)F FDG PET/CT findings were assessed as prognostic factors according to histopathological subtypes. RESULTS: Of 271 patients, 47 (17 %) had a recurrent event. Positive (18)F-FDG cancer uptake was shown in 149 patients (55 %). Tumour size, depth of invasion, presence of lymph node metastasis, positive (18)F-FDG uptake and SUV(max) were significantly associated with tumour recurrence in univariate analysis, while only depth of invasion, positive (18)F-FDG uptake and SUV(max) had significance in multivariate analysis. The 24-month recurrence-free survival rate was significantly higher in patients with negative (18)F-FDG uptake (95 %) than in those with positive (18)F-FDG uptake (74 %; p < 0.0001). In subgroup analysis, (18)F-FDG uptake was a significant prognostic factor in patients with tubular adenocarcinoma (p = 0.003) or poorly differentiated adenocarcinoma (p = 0.0001). However, only marginal significance was shown in patients with signet-ring cell carcinoma and mucinous carcinoma (p = 0.05). CONCLUSION: (18)F-FDG uptake of gastric cancer is an independent and significant prognostic factor for tumour recurrence. (18)F-FDG PET/CT could provide effective information on the prognosis after surgical resection of gastric cancer, especially in tubular adenocarcinoma and poorly differentiated adenocarcinoma. PMID- 22673976 TI - Clinical trial website struggles to serve as research data hub. PMID- 22673977 TI - Pharma backs latest attempt at a global health R&D treaty. PMID- 22673979 TI - Panel proposes framework for FDA to evaluate drug risks. PMID- 22673980 TI - Paper reveals new channels for worry over long QT syndrome. PMID- 22673981 TI - Drugs targeting mGluR5 receptor offer 'fragile' hope for autism. PMID- 22673982 TI - Recommendation of HIV test brings diagnostic dilemma home. PMID- 22673983 TI - Cancer drug's survivin suppression called into question. PMID- 22673984 TI - Sequencing cells one at a time offers singular insight into cancer. PMID- 22673985 TI - A history of drugs on the weight list. PMID- 22673987 TI - Straight talk with...Joseph Schwartz. AB - On 17 May, Human Genome Sciences (HGS) formally rejected a $2.6 billion unsolicited takeover offer by GlaxoSmithKline. The Maryland-based biotech firm had long partnered with the UK drug giant to develop drugs including Benlysta (belimumab), HGS's first drug on the market and the first new medicine approved to fight lupus in 50 years. But, at $13 a share, GSK's bid was deemed "inadequate" by the HGS board. Recent history in the biotech sector shows how high the stakes are in such negotiations. Since last November, six biopharma buyouts have exceeded $1 billion each, with Gilead Sciences' purchase last year of the hepatitis C specialist Pharmasset topping the charts at a whopping $11.2 billion, the highest ever paid for a clinical-stage biotech and an 89% premium to its share price at the time. More recently, in April AstraZeneca paid $1.3 billion for Ardea Biosciences, a company with cancer and gout drugs in the pipeline but nothing on the market.One person watching the upward clime of such deals is biopharma analyst Joseph Schwartz, a managing director at Leerink Swann in Boston. Mark Ratner sought out Schwartz, who was named the top stock picker for pharmaceuticals in the last year's FT/StarMine Analyst Awards, for his views on what's behind the recent buyout spending. PMID- 22673988 TI - The vetting process. PMID- 22673989 TI - Take Russia to 'task' on bioweapons transparency. AB - In the run-up to his reelection, Russian president Vladimir Putin outlined 28 tasks to be undertaken by his administration, including one that commanded the development of weapons based on "genetic principles." Political pressure must be applied by governments and professional societies to ensure that there is not a modern reincarnation of the Soviet biological warfare program. PMID- 22673991 TI - Melanoma exosomes: messengers of metastasis. PMID- 22673992 TI - FOXO3a and beta-catenin co-localization: double trouble in colon cancer? PMID- 22673993 TI - Nicotine: linking smoking to abdominal aneurysms. PMID- 22673994 TI - Peroxiredoxin sets the brain on fire after stroke. PMID- 22673995 TI - New clues to bariatric surgery's benefits. PMID- 22673996 TI - Ephrin receptor: a door to KSHV infection. PMID- 22673997 TI - The secrets of the bone marrow niche: Enigmatic niche brings challenge for HSC expansion. PMID- 22673998 TI - The secrets of the bone marrow niche: Metabolic priming for AML. PMID- 22674008 TI - Reactive intermediates in the H-phosphonate synthesis of oligonucleotides. AB - The formation of H-phosphonate diesters is an important step in the synthesis of oligonucleotides. Using diphenylchlorophosphate as the activator for the coupling step is often accompanied by side reactions as a result of self 'capping' and other reactions of the reactive intermediate. In the absence of base, the activation of ethyl H-phosphonate with diphenylchlorophosphate probably occurs through the intermediate formation of bis diethyl pyro-di-H-phosphonate rather than the expected diphenyl ethyl pyro-H-phosphonate. Pyridine acts as a nucleophilic catalyst converting diphenylchlorophosphate to its pyridinium adduct. Several side and unwanted reactions are quantified so that conditions to minimise these can be identified. PMID- 22674006 TI - Taming lupus-a new understanding of pathogenesis is leading to clinical advances. AB - Systemic lupus erythematosus (SLE) is an autoimmune disease that is characterized by the loss of tolerance to nuclear self antigens, the production of pathogenic autoantibodies and damage to multiple organ systems. Over the years, patients with SLE have been managed largely with empiric immunosuppressive therapies, which are associated with substantial toxicities and do not always provide adequate control of the disease. The development of targeted therapies that specifically address disease pathogenesis or progression has lagged, largely because of the complex and heterogeneous nature of the disease, as well as difficulties in designing uniform outcome measures for clinical trials. Recent advances that could improve the treatment of SLE include the identification of genetic variations that influence the risk of developing the disease, an enhanced understanding of innate and adaptive immune activation and regulation of tolerance, dissection of immune cell activation and inflammatory pathways and elucidation of mechanisms and markers of tissue damage. These discoveries, together with improvements in clinical trial design, form a platform from which to launch the development of a new generation of lupus therapies. PMID- 22674009 TI - Receptor-interacting protein (RIP) and Sirtuin-3 (SIRT3) are on opposite sides of anoikis and tumorigenesis. AB - BACKGROUND: Regulating cross-talk between anoikis and survival signaling pathways is crucial to regulating tissue processes and mitigating diseases like cancer. Previously, the authors demonstrated that anoikis activates a signaling pathway involving the CD95/Fas-mediated signaling pathway that is regulated by receptor interacting protein (RIP), a kinase that shuttles between Fas-mediated cell death and integrin/focal adhesion kinase (FAK)-mediated survival pathways. Because it is known that sirtuin-3 (SIRT3), a nicotinamide adenine dinucleotide-dependent deacetylase, regulates cell survival, metabolism, and tumorigenesis, the authors hypothesized that SIRT3 may engage in cross-talk with Fas/RIP/integrin/FAK survival-death pathways in cancer cell systems. METHODS: Using immunohistochemical staining, immunoblotting, human tissue microarrays, and overexpression and suppression approaches in vitro and in vivo, the roles of RIP and SIRT3 were examined in oral squamous cell carcinoma (OSCC) anoikis resistance and tumorigenesis. RESULTS: RIP and SIRT3 had opposite expression profiles in OSCC cells and tissues. Stable suppression of RIP enhanced SIRT3 levels, whereas stable suppression of SIRT3 did not impact RIP levels in OSCC cells. The authors observed that, as OSCC cells became anoikis-resistant, they formed multicellular aggregates or oraspheres in suspension conditions, and their expression of SIRT3 increased as their RIP expression decreased. Also, anoikis-resistant OSCC cells with higher SIRT3 and low RIP expression induced an increased tumor burden and incidence in mice, unlike their adherent OSCC cell counterparts. Furthermore, stable suppression of SIRT3 inhibited anoikis resistance and reduced tumor incidence. CONCLUSIONS: The current results indicted that RIP is a likely upstream, negative regulator of SIRT3 in anoikis resistance, and an anoikis resistant orasphere phenotype defined by higher SIRT3 and low RIP expression contributes to a more aggressive phenotype in OSCC development. PMID- 22674010 TI - The interactive systems framework applied to the strategic prevention framework: the Rhode Island experience. AB - The Interactive Systems Framework for Dissemination and Implementation (ISF) was introduced as a heuristic systems level model to help bridge the gap between research and practice (Wandersman et al., in Am J Commun Psychol 41:171-181, 2008). This model describes three interacting systems with distinct functions that (1) distill knowledge to develop innovations; (2) provide supportive training and technical assistance for dissemination to; (3) a prevention delivery system responsible for implementation in the field. The Strategic Prevention Framework (SPF) is a major prevention innovation launched by the Center for Substance Abuse Prevention (CSAP) of the Substance Abuse and Mental Health Services Administration (SAMHSA). The SPF offers a structured, sequential, data driven approach that explicitly targets environmental conditions in the community and aims for change in substance use and problems at the population level. This paper describes how the ISF was applied to the challenges of implementing the SPF in 14 Rhode Island communities, with a focus on the development of a new Training and Technical Assistance Resources Center to support SPF efforts. More specifically, we (1) describe each of the three ISF interacting systems as they evolved in Rhode Island; (2) articulate the lines of communication between the three systems; and (3) examine selected evaluation data to understand relationships between training and technical assistance and SPF implementation and outcomes. PMID- 22674011 TI - Brief report: amelioration of collagen-induced arthritis in mice by lentivirus mediated silencing of microRNA-223. AB - OBJECTIVE: MicroRNA (miRNA) plays a role in autoimmune diseases. MiRNA-223 (miR 223) is up-regulated in patients with rheumatoid arthritis (RA) and is involved in osteoclastogenesis, which contributes to erosive disease. The aim of this study was to test the feasibility of using lentiviral vectors expressing the miR 223 target sequence (miR-223T) to suppress miR-223 activity as a therapeutic strategy in a mouse model of collagen-induced arthritis (CIA). METHODS: Levels of miR-223 in the synovial tissue of patients with RA or osteoarthritis (OA), as well as in the ankle joints of mice with CIA, were determined by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Lentiviral vectors expressing miR-223T (LVmiR-223T) or luciferase short hairpin RNA (LVshLuc) as a control vector were injected intraperitoneally into mice with CIA. Treatment responses and disease-related bone mineral density were monitored. Levels of nuclear factor 1A (NF-1A), a direct target of miR-223, and macrophage colony stimulating factor receptor (M-CSFR), which is critical for osteoclastogenesis, were measured by immunohistochemistry and quantitative RT-PCR. Osteoclasts were assessed by tartrate-resistant acid phosphatase staining. RESULTS: MiR-223 expression was significantly higher in the synovium of RA patients and in the ankle joints of mice with CIA as compared to OA patients and normal mice. LVmiR 223T treatment reduced the arthritis score, histologic score, miR-223 expression, osteoclastogenesis, and bone erosion in mice with CIA. Down-regulation of miR-223 with concomitant increases in NF-1A levels and decreases in M-CSFR levels was detected in the synovium of LVmiR-223T-treated mice. CONCLUSION: This study is the first to demonstrate that lentivirus-mediated silencing of miR-223 can reduce disease severity of experimental arthritis. Furthermore, our results indicate that inhibition of miR-223 activity should be further explored as a therapeutic strategy in RA. PMID- 22674012 TI - Association of anti-citrullinated vimentin and anti-citrullinated alpha-enolase antibodies with subsets of rheumatoid arthritis. AB - OBJECTIVE: To determine whether the anti-citrullinated vimentin peptide 60-75 (anti-Cit-vimentin) and the immunodominant anti-citrullinated alpha-enolase peptide 1 (anti-CEP-1) antibodies are associated with subsets of patients with rheumatoid arthritis (RA) independently of the associations between anti-cyclic citrullinated peptide (anti-CCP) antibodies and clinical features of RA. METHODS: The 3 antibody types were quantified by enzyme-linked immunosorbent assay (ELISA) in serum samples from 521 patients with RA and 173 healthy controls of Spanish ancestry. Genotypes for HLA-DRB1 alleles and rs2476601 in PTPN22 were available for these patients and controls plus an additional 106 healthy controls. A combined analysis of the 3 antibodies was conducted using stratified contingency tables and logistic regression models. RESULTS: A differential, particularly strong, and independent association was observed between the presence of anti-Cit vimentin antibodies and the presence of shared epitope (SE) alleles, specifically in patients carrying 2 SE alleles, and between the presence of anti- Cit-vimentin antibodies and the prevalence of joint erosion. Associations were observed between anti-CEP-1 positivity and the presence of HLA-DRB1 and PTPN22 risk alleles and their additive interaction. These associations were not accounted for by the anti-CCP status. CONCLUSION: Our results indicate that the 2 antibodies against citrullinated peptides analyzed in this study add specific information beyond that obtained with the anti-CCP status. They define subgroups of patients with RA in which genetic factors have different weight and there is an observed difference in the prevalence of erosions. PMID- 22674013 TI - The reversible formation of cysteine sulfenic acid promotes B-cell activation and proliferation. AB - B-cell receptor (BCR) ligation generates reactive oxygen intermediates (ROIs) that play a role in cellular responses. Although ROIs can oxidize all macromolecules, it was unclear which modifications control B-cell responses. In this study, we demonstrate the importance of the first oxidation product of cysteine, sulfenic acid, and its reversible formation in B-cell activation. Upon BCR crosslinking, B cells increase ROI levels with maximal production occurring within 15 min. Increased ROIs preceded elevated cysteine sulfenic acid, which localized to the cytoplasm and nucleus. Analysis of individual proteins revealed that the protein tyrosine phosphatases (PTPs) SHP-1, SHP-2, and PTEN, as well as actin, were modified to sulfenic acid following BCR ligation. Additionally, we used 5,5-dimethyl-1,3-cyclohexanedione (dimedone), a compound that covalently reacts with sulfenic acid to prevent its further oxidation or reduction, to determine the role of reversible cysteine sulfenic acid formation in regulating B cell responses. Dimedone incubation resulted in a concentration-dependent block in anti-IgM-induced cell division, accompanied by a failure to induce capacitative calcium entry (CCE), and maintain tyrosine phosphorylation. These studies illustrate that reversible cysteine sulfenic acid formation is a mechanism by which B cells modulate pathways critical for activation and proliferation. PMID- 22674015 TI - Behcet syndrome: is it one condition? AB - Behcet's syndrome (BS) is a disease of unknown etiology, and as such, there have been efforts to classify BS within the popular nosological identities of the times such as seronegative spondarthritides, autoimmune, and more recently autoinflammatory diseases. Current evidence suggests that BS does not easily fit into any one of these lumps, while on occasion, it might be impossible to tell BS from Crohn's disease, especially when the main clinical presentation is intestinal ulceration. There are distinct regional differences in disease expression of BS with fewer cases of intestinal disease in the Mediterranean basin and less severe eye disease and less frequent skin pathergy among patients reported from northern Europe or America. The clustering of symptoms, especially with the recently described increased frequency of the acne/arthritis cluster in familial cases, suggests that more than one pathological pathway is involved in what we call BS today. Supportive evidence for this contention also comes from the observations that (a) the genetic component is very complex with perhaps different genetic modes of inheritance in the adult and in the pediatric patients; and (b) there are differing organ responses to one same drug. For example, the anti-TNF agents successfully control the oral ulcers while they have no effect on the pathergy reaction. PMID- 22674016 TI - Pathogenic intracellular and autoimmune mechanisms in urticaria and angioedema. AB - Urticaria and angioedema are common disorders. Chronic urticaria is defined as lasting longer than 6 weeks. Causes of chronic urticaria fall into the following categories: physical, allergic, hereditary, autoimmune, and idiopathic. Basophils and mast cells are the primary effector cells responsible for clinical symptoms and signs. These cells produce and secrete a variety of mediators including histamine, leukotrienes, prostaglandins, cytokines, chemokines, and other pro inflammatory mediators. This leads to vasodilation, fluid exudation, increased vascular permeability, and accumulation of additional secondary inflammatory cells. Two mechanisms have been investigated as possibly contributing to the pathogenesis of chronic urticaria. One is the development of autoantibodies to FcepsilonRI or IgE on mast cells and basophils. This appears to be responsible for 30-50 % of cases. The other is dysregulation of intracellular signaling pathways involving Syk, SHIP-1, or SHIP-2 in basophils and mast cells. The primary treatment for chronic urticaria is to treat the underlying pathology, if any can be identified. Otherwise, in idiopathic cases, H1 antihistamines, H2 antihistamines, antileukotrienes, and corticosteroids constitute the main pharmacologic treatment modalities. In severe and recalcitrant cases of chronic and autoimmune urticaria, immunosuppressive drugs have been used, most commonly cyclosporin. More recent experimental studies have also suggested that omalizumab, an anti-IgE therapy, may be of benefit. Currently, inhibitors of Syk are also being developed and tested in the laboratory and in animal models. As our understanding of the pathogenesis of idiopathic urticaria increases, development of additional drugs targeting these pathways may provide relief for the significant physical and psychological morbidity experienced by patients with this disorder. PMID- 22674017 TI - Systemic lupus erythematosus, progressive multifocal leukoencephalopathy, and T CD4+ lymphopenia. AB - Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic infection caused by the reactivation of JC virus and occurs in patients with severe primary or secondary immunosuppression. Recently, PML is becoming relevant in autoimmune disorders, particularly in patients treated with biologic agents. However, systemic lupus erythematosus (SLE) appears to be associated with susceptibility to PML that cannot be entirely explained by the immunosuppressive therapy. The authors present two patients with the diagnosis of SLE and PML: One had a heavy immunosuppressive therapy history, and the other had never experienced biologic or cytotoxic therapeutics. Both patients had a profound T CD4+ lymphopenia during their clinical history. These two cases emphasize the importance of CD4+ lymphopenia in SLE patients with and without immunosuppressors regarding opportunistic infections. PMID- 22674018 TI - Primary small cell carcinoma of the stomach: an experience of two decades (1990 2011) in a Chinese cancer institute. AB - BACKGROUND: Primary gastric small cell carcinoma (GSCC) is a rare and aggressive disease for which the standard treatment has not been established. The objective of this study is to investigate the clinical characteristics and survival. METHODS: All cases of GSCC treated at our institute from January 1990 to December 2011 were reviewed and analyzed retrospectively. Statistical analyses were performed using Fisher's exact test. RESULTS: A total of 19 patients from 11,603 cases (0.16%) of all gastric cancers treated during this period were identified. The median age was 61 years and the patients were predominantly men. Using the latest AJCC Staging Criteria, the majority of the patients (68.4%) were Stage III. All patients underwent surgery. The median overall survival time (MST) was 19.5 months (95% CI 17.5-21.6 months). The 1-, 3-, and 5-year overall survival rates were 77.3%, 44.2%, and 22.1%, respectively. The MST of 48.5 months for cases who received postoperative adjuvant chemotherapy was superior to that of 19.0 months for cases who did not (P = 0.026). CONCLUSIONS: Our data indicate that GSCC patients can be treated effectively with combined modality of treatment, despite the aggressive nature of GSCC. Systemic therapy, based on chemotherapy with surgery, is recommended. PMID- 22674019 TI - Impact of future warming on winter chilling in Australia. AB - Increases in temperature as a result of anthropogenically generated greenhouse gas (GHG) emissions are likely to impact key aspects of horticultural production. The potential effect of higher temperatures on fruit and nut trees' ability to break winter dormancy, which requires exposure to winter chilling temperatures, was considered. Three chill models (the 0-7.2 degrees C, Modified Utah, and Dynamic models) were used to investigate changes in chill accumulation at 13 sites across Australia according to localised temperature change related to 1, 2 and 3 degrees C increases in global average temperatures. This methodology avoids reliance on outcomes of future GHG emission pathways, which vary and are likely to change. Regional impacts and rates of decline in chilling differ among the chill models, with the 0-7.2 degrees C model indicating the greatest reduction and the Dynamic model the slowest rate of decline. Elevated and high latitude eastern Australian sites were the least affected while the three more maritime, less elevated Western Australian locations were shown to bear the greatest impact from future warming. PMID- 22674020 TI - Twenty years of telemedicine in chronic disease management--an evidence synthesis. AB - A literature review was conducted to obtain a high-level view of the value of telemedicine in the management of five common chronic diseases (asthma, COPD, diabetes, heart failure, hypertension). A total of 141 randomised controlled trials (RCTs) was identified, in which 148 telemedicine interventions of various kinds had been tested in a total of 37,695 patients. The value of each intervention was categorised in terms of the outcomes specified by the investigators in that trial, i.e. no attempt was made to extract a common outcome from all studies, as would be required for a conventional meta-analysis. Summarizing the value of these interventions shows, first, that most studies have reported positive effects (n = 108), and almost none have reported negative effects (n = 2). This suggests publication bias. Second, there were no significant differences between the chronic diseases, i.e. telemedicine seems equally effective (or ineffective) in the diseases studied. Third, most studies have been relatively short-term (median duration 6 months). It seems unlikely that in a chronic disease, any intervention can have much effect unless applied for a long period. Finally, there have been very few studies of cost effectiveness. Thus the evidence base for the value of telemedicine in managing chronic diseases is on the whole weak and contradictory. PMID- 22674022 TI - Diffusive oxygen shunting between vessels in the preglomerular renal vasculature: anatomic observations and computational modeling. AB - To understand how geometric factors affect arterial-to-venous (AV) oxygen shunting, a mathematical model of diffusive oxygen transport in the renal cortex was developed. Preglomerular vascular geometry was investigated using light microscopy (providing vein shape, AV separation, and capillary density near arteries) and published micro-computed tomography (CT) data (providing vessel size and AV separation; Nordsletten DA, Blackett S, Bentley MD, Ritman EL, Smith NP. IUPS Physiome Project. http://www.physiome.org.nz/publications/nordsletten_blackett_ritman_bentley_smith 2005/folder_contents). A "U-shaped" relationship was observed between the arterial radius and the distance between the arterial and venous lumens. Veins were found to partially wrap around the artery more consistently for larger rather than smaller arteries. Intrarenal arteries were surrounded by an area of fibrous tissue, lacking capillaries, the thickness of which increased from ~5 MUm for the smallest arteries (<16-MUm diameter) to ~20 MUm for the largest arteries (>200-MUm diameter). Capillary density was greater near smaller arteries than larger arteries. No capillaries were observed between wrapped AV vessel pairs. The computational model comprised a single AV pair in cross section. Geometric parameters critical in renal oxygen transport were altered according to variations observed by CT and light microscopy. Lumen separation and wrapping of the vein around the artery were found to be the critical geometric factors determining the amount of oxygen shunted between AV pairs. AV oxygen shunting increases both as lumen separation decreases and as the degree of wrapping increases. The model also predicts that capillaries not only deliver oxygen, but can also remove oxygen from the cortical parenchyma close to an AV pair. Thus the presence of oxygen sinks (capillaries or tubules) near arteries would reduce the effectiveness of AV oxygen shunting. Collectively, these data suggest that AV oxygen shunting would be favored in larger vessels common to the cortical and medullary circulations (i.e., arcuate and proximal interlobular arteries) rather than the smaller vessels specific to the cortical circulation (distal interlobular arteries and afferent arterioles). PMID- 22674023 TI - Protein kinase C-alpha activation promotes recovery of mitochondrial function and cell survival following oxidant injury in renal cells. AB - We demonstrated that nonselective PKC activation promotes mitochondrial function in renal proximal tubular cells (RPTC) following toxicant injury. However, the specific PKC isozyme mediating this effect is unknown. This study investigated the role of PKC-alpha in the recovery of mitochondrial functions in oxidant injured RPTC. Wild-type PKC-alpha (wtPKC-alpha) and inactive PKC-alpha mutants were overexpressed in RPTC to selectively increase or block PKC-alpha activation. Oxidant (tert-butyl hydroperoxidel; TBHP) exposure activated PKC-alpha in RPTC but decreased PKC-alpha levels in mitochondria following treatment. Uncoupled and state 3 respirations and activities of complexes I and IV in TBHP-injured cells decreased to 55, 44, 49, and 65% of controls, respectively. F(0)F(1)-ATPase activity and ATP content in injured RPTC decreased to 59 and 60% of controls, respectively. Oxidant exposure increased reactive oxygen species (ROS) production by 210% and induced mitochondrial fragmentation and 52% RPTC lysis. Overexpressing wtPKC-alpha did not block TBHP-induced ROS production but improved respiration and complex I activity, restored complex IV and F(0)F(1)-ATPase activities, promoted recovery of ATP content, blocked mitochondrial fragmentation, and reduced RPTC lysis to 14%. In contrast, inhibiting PKC-alpha 1) induced mitochondrial hyperpolarization and fragmentation; 2) blocked increases in ROS production; 3) prevented recovery of respiratory complexes and F(0)F(1)-ATPase activities, respiration, and ATP content; and 4) exacerbated TBHP induced RPTC lysis. We conclude that 1) activation of PKC-alpha prevents mitochondrial hyperpolarization and fragmentation, decreases cell death, and promotes recovery of mitochondrial respiration and ATP content following oxidant injury in RPTC; and 2) respiratory complexes I and IV and F(0)F(1)-ATPase are targets of active PKC-alpha. PMID- 22674024 TI - Nebivolol-induced vasodilation of renal afferent arterioles involves beta3 adrenergic receptor and nitric oxide synthase activation. AB - Nebivolol is a beta(1)-adrenergic blocker that also elicits renal vasodilation and increases the glomerular filtration rate (GFR). However, its direct actions on the renal microvasculature and vasodilator mechanism have not been established. We used the in vitro blood-perfused juxtamedullary nephron technique to determine the vasodilator effects of nebivolol and to test the hypothesis that nebivolol induces vasodilation of renal afferent arterioles via an nitric oxide synthase (NOS)/nitric oxide (NO)/soluble guanylate cyclase (sGC)/cGMP pathway and the afferent arteriolar vasodilation effect may be mediated through the release of NO by activation of NOS via a beta(3)-adrenoceptor-dependent mechanism. Juxtamedullary nephrons were superfused with nebivolol either alone or combined with the sGC inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) or the NOS inhibitor N(omega)-nitro-l-arginine (l-NNA) or the beta-blockers metoprolol (beta(1)), butoxamine (beta(2)), and SR59230A (beta(3)). Nebivolol (100 MUmol/l) markedly increased afferent and efferent arteriolar diameters by 18.9 +/- 3.0 and 15.8 +/- 1.8%. Pretreatment with l-NNA (1,000 MUmol/l) or ODQ (10 MUmol/l) decreased afferent vasodilator diameters and prevented the vasodilator effects of nebivolol (2.0 +/- 0.2 and 2.4 +/- 0.6%). Metoprolol did not elicit significant changes in afferent vasodilator diameters and did not prevent the effects of nebivolol to vasodilate afferent arterioles. However, treatment with SR59230A, but not butoxamine, markedly attenuated the vasodilation responses to nebivolol. Using a monoclonal antibody to beta(3)-receptors revealed predominant immunostaining on vascular and glomerular endothelial cells. These data indicate that nebivolol vasodilates both afferent and efferent arterioles and that the afferent vasodilator effect is via a mechanism that is independent of beta(1) receptors but is predominantly mediated via a NOS/NO/sGC/cGMP-dependent mechanisms initiated by activation of endothelial beta(3)-receptors. PMID- 22674025 TI - A fluorogenic near-infrared imaging agent for quantifying plasma and local tissue renin activity in vivo and ex vivo. AB - The renin-angiotensin system (RAS) is well studied for its regulation of blood pressure and fluid homeostasis, as well as for increased activity associated with a variety of diseases and conditions, including cardiovascular disease, diabetes, and kidney disease. The enzyme renin cleaves angiotensinogen to form angiotensin I (ANG I), which is further cleaved by angiotensin-converting enzyme to produce ANG II. Although ANG II is the main effector molecule of the RAS, renin is the rate-limiting enzyme, thus playing a pivotal role in regulating RAS activity in hypertension and organ injury processes. Our objective was to develop a near infrared fluorescent (NIRF) renin-imaging agent for noninvasive in vivo detection of renin activity as a measure of tissue RAS and in vitro plasma renin activity. We synthesized a renin-activatable agent, ReninSense 680 FAST (ReninSense), using a NIRF-quenched substrate derived from angiotensinogen that is cleaved specifically by purified mouse and rat renin enzymes to generate a fluorescent signal. This agent was assessed in vitro, in vivo, and ex vivo to detect and quantify increases in plasma and kidney renin activity in sodium-sensitive inbred C57BL/6 mice maintained on a low dietary sodium and diuretic regimen. Noninvasive in vivo fluorescence molecular tomographic imaging of the ReninSense signal in the kidney detected increased renin activity in the kidneys of hyperreninemic C57BL/6 mice. The agent also effectively detected renin activity in ex vivo kidneys, kidney tissue sections, and plasma samples. This approach could provide a new tool for assessing disorders linked to altered tissue and plasma renin activity and to monitor the efficacy of therapeutic treatments. PMID- 22674026 TI - Cystogenesis and elongated primary cilia in Tsc1-deficient distal convoluted tubules. AB - Tuberous sclerosis complex (TSC) is a multiorgan hamartomatous disease caused by loss of function mutations of either the TSC1 or TSC2 genes. Neurological symptoms of TSC predominate in younger patients, but renal pathologies are a serious aspect of the disease in older children and adults. To study TSC pathogenesis in the kidney, we inactivated the mouse Tsc1 gene in the distal convoluted tubules (DCT). At young ages, Tsc1 conditional knockout (CKO) mice have enlarged kidneys and mild cystogenesis with increased mammalian target of rapamycin complex (mTORC)1 but decreased mTORC2 signaling. Treatment with the mTORC1 inhibitor rapamycin reduces kidney size and cystogenesis. Rapamycin withdrawal led to massive cystogenesis involving both distal as well as proximal tubules. To assess the contribution of decreased mTORC2 signaling in kidney pathogenesis, we also generated Rictor CKO mice. These animals did not have any detectable kidney pathology. Finally, we examined primary cilia in the DCT. Cilia were longer in Tsc1 CKO mice, and rapamycin treatment returned cilia length to normal. Rictor CKO mice had normal cilia in the DCT. Overall, our findings suggest that loss of the Tsc1 gene in the DCT is sufficient for renal cystogenesis. This cytogenesis appears to be mTORC1 but not mTORC2 dependent. Intriguingly, the mechanism may be cell autonomous as well as non-cell autonomous and possibly involves the length and function of primary cilia. PMID- 22674029 TI - Optimizing decision making for late-phase recovery one year after the Fukushima nuclear accident. PMID- 22674027 TI - Loss of renal medullary endothelin B receptor function during salt deprivation is regulated by angiotensin II. AB - We have recently demonstrated that chronic infusion of exogenous ANG II, which induces blood pressure elevation, attenuates renal medullary endothelin B (ET(B)) receptor function in rats. Moreover, this was associated with a reduction of ET(B) receptor expression in the renal inner medulla. The aim of this present work was to investigate the effect of a physiological increase in endogenous ANG II (low-salt diet) on the renal ET system, including ET(B) receptor function. We hypothesized that endogenous ANG II reduces renal medullary ET(B) receptor function during low-salt intake. Rats were placed on a low-salt diet (0.01-0.02% NaCl) for 2 wk to allow an increase in endogenous ANG II. In rats on normal-salt chow, the stimulation of renal medullary ET(B) receptor by ET(B) receptor agonist sarafotoxin 6c (S6c) causes an increase in water (3.6 +/- 0.4 from baseline vs. 10.5 +/- 1.3 MUl/min following S6c infusion; P < 0.05) and sodium excretion (0.38 +/- 0.06 vs. 1.23 +/- 0.17 MUmol/min; P < 0.05). The low-salt diet reduced the ET(B)-dependent diuresis (4.5 +/- 0.5 vs. 6.1 +/- 0.9 MUl/min) and natriuresis (0.40 +/- 0.11 vs. 0.46 +/- 0.12 MUmol/min) in response to acute intramedullary infusion of S6c. Chronic treatment with candesartan restored renal medullary ET(B) receptor function; urine flow was 7.1 +/- 0.9 vs. 15.9 +/- 1.7 MUl/min (P < 0.05), and sodium excretion was 0.4 +/- 0.1 vs. 1.1 +/- 0.1 MUmol/min (P < 0.05) before and after intramedullary S6c infusion, respectively. Receptor binding assays determined that the sodium-depleted diet resulted in a similar level of ET(B) receptor binding in renal inner medulla compared with rats on a normal-salt diet. Candesartan reduced renal inner medullary ET(B) receptor binding (1,414 +/- 95 vs. 862 +/- 50 fmol/mg; P < 0.05). We conclude that endogenous ANG II attenuates renal medullary ET(B) receptor function to conserve sodium during salt deprivation independently of receptor expression. PMID- 22674028 TI - Membrane-associated aquaporin-1 facilitates osmotically driven water flux across the basolateral membrane of the thick ascending limb. AB - The thick ascending limb of the loop of Henle (TAL) reabsorbs ~30% of filtered NaCl but is impermeable to water. The observation that little water traverses the TAL indicates an absence of water channels at the apical membrane. Yet TAL cells swell when peritubular osmolality decreases indicating that water channels must be present in the basolateral side. Consequently, we hypothesized that the water channel aquaporin-1 (AQP1) facilitates water flux across the basolateral membrane of TALs. Western blotting revealed AQP1 expression in microdissected rat and mouse TALs. Double immunofluorescence showed that 95 +/- 2% of tubules positive for the TAL-specific marker Tamm-Horsfall protein were also positive for AQP1 (n = 6). RT-PCR was used to demonstrate presence of AQP1 mRNA and the TAL-specific marker NKCC2 in microdissected TALs. Cell surface biotinylation assays showed that 23 +/- 3% of the total pool of AQP1 was present at the TAL basolateral membrane (n = 7). To assess the functional importance of AQP1 in the basolateral membrane, we measured the rate of cell swelling initiated by decreasing peritubular osmolality as an indicator of water flux in microdissected TALs. Water flux was decreased by ~50% in Aqp1 knockout mice compared with wild-types (4.0 +/- 0.8 vs. 8.9 +/- 1.7 fluorescent U/s, P < 0.02; n = 7). Furthermore, arginine vasopressin increased TAL AQP1 expression by 135 +/- 17% (glycosylated) and 41 +/- 11% (nonglycosylated; P < 0.01; n =5). We conclude that 1) the TAL expresses AQP1, 2) ~23% of the total pool of AQP1 is localized to the basolateral membrane, 3) AQP1 mediates a significant portion of basolateral water flux, and 4) AQP1 is upregulated in TALs of rats infused with dDAVP. AQP1 could play an important role in regulation of TAL cell volume during changes in interstitial osmolality, such as during a high-salt diet or water deprivation. PMID- 22674030 TI - The Gilliatt-Sumner hand. PMID- 22674031 TI - Artificial neural networks based early clinical prediction of mortality after spontaneous intracerebral hemorrhage. AB - Numerous outcome prediction models have been developed for mortality and functional outcome after spontaneous intracerebral haemorrhage (ICH). However, no outcome prediction model for ICH has considered the impact of care restriction. To develop and compare results of the artificial neural networks (ANN) and logistic regression (LR) models, based on initial clinical parameters, for prediction of mortality after spontaneous ICH. Analysis has been conducted on consecutive dataset of patients with spontaneous ICH, over 5-year period in tertiary care academic hospital. Patients older than 18 years were eligible for inclusion if they had been presented within 6 h from the start of symptoms and had evidence of spontaneous supratentorial ICH on initial brain computed tomography within 24 h. Initial clinical parameters have been used to develop LR and ANN prediction models for hospital mortality as outcome measure. Models have been accessed for discrimination and calibration abilities. We have analyzed 411 patients (199 males and 212 females) with spontaneous ICH, medically treated and not withdrawn from therapy, with average age of 67.35 years. From them, 256 (62.29%) patients died during hospital treatment and 155 (37.71%) patients survived. In the observed dataset, ANN model overall correctly classified outcome in 93.55% of patients, compared with 79.32% of correct classification for the LR model. Discrimination and calibration parameters indicate that both models show an adequate fit of expected and observed values, with superiority of ANN model. Our results favour the ANN model for prediction of mortality after spontaneous ICH. Further studies of the strengths and limitations of this method are needed with larger prospective samples. PMID- 22674034 TI - Smad3 controls beta-1,3-glucuronosyltransferase 1 expression in rat nucleus pulposus cells: implications of dysregulated expression in disc disease. AB - OBJECTIVE: To study the regulation of expression of beta-1,3 glucuronosyltransferase 1 (GlcAT-1), an important regulator of glycosaminoglycan (GAG) synthesis, by Smad3 in nucleus pulposus (NP) cells. METHODS: GlcAT-1 expression was examined in rat NP and anulus fibrosus (AF) cells treated with transforming growth factor beta (TGFbeta). The effects of Smad signaling and Smad suppression on GlcAT-1 were examined in rat NP cells. GlcAT-1 expression was analyzed in the discs of Smad3-null mice and in degenerated human NP tissue. RESULTS: TGFbeta increased the expression of GlcAT-1 in rat NP but not rat AF cells. Suppression of GlcAT-1 promoter activity was evident with dominant negative ALK-5 (DN-ALK-5). Cotransfection with Smad3 strongly induced promoter activity independent of TGFbeta. Bioinformatics analysis indicated the presence of several Smad binding sites in the promoter; deletion analysis showed that the region between -274 and -123 bp was required for Smad3 response. DN-Smad3, Smad 3 small interfering RNA, and Smad7 strongly suppressed basal as well as TGFbeta induced promoter activity. Induction of promoter activity by Smad3 was significantly blocked by DN-Smad3; Smad7 had a very small effect. Lentiviral transduction of NP cells with short hairpin RNA Smad3 resulted in a decrease in GlcAT-1 expression and accumulation of GAG. Compared to wild-type mice, significantly lower expression of GlcAT-1 was seen in the discs of Smad3-null mice. Analysis of degenerated human NP tissue specimens showed no positive correlation between GlcAT-1 and TGFbeta expression. Moreover, isolated cells from degenerated human tissue showed a lack of induction of GlcAT-1 expression following TGFbeta treatment, suggesting an altered response. CONCLUSION: Our findings demonstrate that in healthy NP cells, the TGFbeta-Smad3 axis serves as a regulator of GlcAT-1 expression. However, an altered responsiveness to TGFbeta during disc degeneration may compromise GAG synthesis. PMID- 22674035 TI - Sexting by high school students: an exploratory and descriptive study. AB - Recently, a phenomenon known as sexting, defined here as the transfer of sexually explicit photos via cell phone, has received substantial attention in the U.S. national media. To determine the current and potential future impact of sexting, more information about the behavior and the attitudes and beliefs surrounding it must be gathered, particularly as it relates to sexting by minors. The present study was designed to provide preliminary information about this phenomenon. Participants were 606 high school students (representing 98 % of the available student body) recruited from a single private high school in the southwestern U.S. Nearly 20 % of all participants reported they had ever sent a sexually explicit image of themselves via cell phone while almost twice as many reported that they had ever received a sexually explicit picture via cell phone and, of these, over 25 % indicated that they had forwarded such a picture to others. Of those reporting having sent a sexually explicit cell phone picture, over a third did so despite believing that there could be serious legal and other consequences attached to the behavior. Given the potential legal and psychological risks associated with sexting, it is important for adolescents, parents, school administrators, and even legislators and law enforcement to understand this behavior. PMID- 22674036 TI - The effect of aging and cancer on the symptom experience and physical function of elderly breast cancer survivors. AB - BACKGROUND: The majority of cancer survivors are aged >= 65 years, yet, historically, cancer research has focused infrequently on older patients. The objective of this study was to examine predictors of physical function within a framework that integrates the gerontologic and oncologic needs of older cancer survivors. METHODS: Path analysis tested 759 women who were breast cancer survivors aged >= 70 years from the American Cancer Society Study of Cancer Survivors II to examine the cancer, aging, and personal characteristics that had an impact on symptoms and physical functioning. RESULTS: High levels of symptom bother (beta = -.42) and comorbidities (beta = -.21) were strongly associated with lower physical function. Comorbidity and social support (beta = .21) indirectly influenced symptom bother through emotional status (beta = -.35). The model demonstrated good fit with the data (chi-square statistic, 50.6; adjusted chi-square statistic, 2.8; P < .001; goodness-of-fit index, .98; root mean square error of approximation, .049 [confidence interval, .03-.05]). CONCLUSIONS: The current findings supported prior research indicating that the majority of older survivors of breast cancer are doing well, but there is a subset of survivors that requires ongoing attention to symptoms, comorbidities, emotional health, and social support to thrive after cancer treatment. PMID- 22674037 TI - An enzyme-encapsulated microreactor for efficient theanine synthesis. AB - A flow-type microreactor containing glutaminase-mesoporous silica composites with 10.6 nm pore diameter (TMPS10.6) was developed for the continuous synthesis of theanine, a unique amino acid. High enzymatic activity was exhibited by the local control of the reaction temperature. PMID- 22674038 TI - Unscheduled return visits with and without admission post emergency department discharge. AB - BACKGROUND: Monitoring unscheduled return visits to the Emergency Department (ED) is useful to identify medical errors. OBJECTIVE: To investigate the differences between unscheduled return visit admissions (URVA) and unscheduled return visit no admissions (URVNA) after ED discharge. METHODS: From January 1, 2008 to March 31, 2008, URVA and URVNA patients who returned within 3 days after ED discharge were enrolled in the study. We compared the clinical characteristics, underlying diseases, ED crowding indicators, staff experience at the patient's first visit, and several other risk factors. We used multivariate logistic regression to evaluate differences between the two groups and to identify predictors of admission from unscheduled return visits. RESULTS: The unscheduled return visit rate was 3.1%. Of the 413 patients included, 147 patients (36%) were admitted, and had a mortality rate of 4.1%. The most common reason for the return visit was an illness-based factor (47.9%). Compared to URVNA patients, unscheduled return visit admissions had higher prevalence rates for old age, non-ambulatory status, high-grade triage, and underlying diseases (e.g., malignancy, diabetes mellitus, hypertension, coronary artery disease, heart failure, and chronic obstructive pulmonary disease). The independent predictors for URVA were: age>=65 years (adjusted odds ratio [OR] 2.2, 95% confidence interval [CI] 1.4-3.5); high-grade triage (adjusted OR 2.1, 95% CI 1.3-3.2); and doctor-based factors (adjusted OR 3.5, 95% CI 2.0-6.1). More advanced staff experience (p=0.490) and ED crowding were not significant predictors (p=0.498 for whole-day number of patients, p=0.095 for whole-shift number of patients). CONCLUSION: Old age, high-grade triage, and doctor-based factors were found to be significant predictors for URVA, whereas advanced staff experience and ED crowding were not. PMID- 22674039 TI - Transcardiac conducted electrical weapon (TASER) probe deployments: incidence and outcomes. AB - BACKGROUND: TASER (TASER International, Scottsdale, AZ) conducted electrical weapons (CEWs) are commonly used by law enforcement officers. Although animal studies have suggested that transcardiac CEW discharges may produce direct cardiac effects, this has not been demonstrated in human studies. OBJECTIVES: This study sought to determine the incidence and outcomes of transcardiac CEW probe impact locations in a large series of actual CEW deployments. METHODS: A multi-center database of consecutive CEW uses by law enforcement officers was retrospectively reviewed. Case report forms were independently reviewed by three investigators to identify cases with paired probe configurations potentially producing a transcardiac discharge vector. Descriptive analysis was performed and inter-rater reliability was assessed. RESULTS: Among 1201 total CEW uses, 813 included probe deployments and 178 cases had paired anterior probe impacts potentially capable of producing a transcardiac discharge vector. This represents 14.8% of all CEW uses (95% confidence interval [CI] 12.9-16.9%) and 21.9% of CEW uses in probe mode (95% CI 19.1-24.9%). Inter-rater agreement was very good, with kappa = 0.82. There were no immediate deaths in any cases (97.5% CI 0.0-0.3%) to suggest a cardiac dysrhythmia, including those with transcardiac discharge vector. CONCLUSION: CEW deployments with probe impact configurations capable of producing a transcardiac discharge occur in a minority of cases in field use conditions. None of these cases, transcardiac or otherwise, produced immediately fatal dysrhythmias. These data support the overall safety of CEWs and provide a benchmark estimate of the likelihood of transcardiac discharge vectors occurring in field use of CEWs. PMID- 22674040 TI - Spontaneous compartment syndrome of the upper arm in a patient receiving anticoagulation therapy. AB - BACKGROUND: Compartment syndrome is a condition in which elevated pressures within an osseofascial compartment cause vascular compromise, leading to ischemia and possible necrosis. It commonly occurs after a traumatic event (e.g., fracture, crush, burn); however, compartment syndrome can happen spontaneously and in any compartment of the body. The objective of this case study is to present the signs and symptoms of upper arm compartment syndrome along with a review of the diagnosis and treatment. CASE REPORT: A 75-year-old man receiving anticoagulation for atrial fibrillation developed compartment syndrome in the extensor compartment of his upper arm, diagnosed by clinical examination with the aid of a venous duplex ultrasound study. CONCLUSION: Although uncommon, spontaneous compartment syndrome can occur, and prompt recognition and intervention are limb- and possibly life-saving. PMID- 22674041 TI - Epidemiology and prognostic factors in cases of near hanging presenting to a referral hospital in Arak, Iran. AB - BACKGROUND: Hanging is a common method of suicide in many countries, and it has a higher success rate than other commonly employed modes of attempted suicide, such as self-poisoning. STUDY OBJECTIVES: The aim of this study was to determine the epidemiology and characteristics of near-hanging patients admitted to the main referral hospital in Arak, Iran. METHODS: All patients with the diagnosis of hanging admitted between January 2000 and 2009 were included in the study. Data regarding demographics, radiographic studies, injuries, Glasgow Coma Scale score (GCS) on arrival, and outcomes, were examined. RESULTS: During the 9-year study period, 43 cases of near hanging were identified. All patients were male, with a mean age of 24.2 years (range: 12-38 years). The median GCS at presentation was 6 (range: 3-12), and 83.8% of patients had a GCS of 8 or less. Cervical spine fracture of C2 was observed in two cases (4%). The imaging studies revealed that 62.7% of patients had an abnormal brain computed tomography scan, with brain edema being the most common finding (n=16, 37.2%), followed by subdural hematoma (n=10, 23.3%). Ophthalmologic examination demonstrated retinal bleeding in 24 patients (55.8%). There were four inpatient deaths among the study group, and 39 patients survived to discharge, yielding a mortality rate of 9.3%. Findings on presentation associated with subsequent mortality included a systolic blood pressure<90 mm Hg, GCS<5, retinal bleeding, and pulmonary edema. CONCLUSION: Mortality among patients who present alive to the hospital after near hanging is low, including those with a low GCS on arrival. Ophthalmoscopic examination, as well as radiological examination of the brain and cervical spine, should be performed in cases of near hanging. PMID- 22674043 TI - Biowaiver monograph for immediate-release solid oral dosage forms: acetylsalicylic acid. AB - A biowaiver monograph for acetylsalicylic acid (ASA) is presented. Literature and experimental data indicate that ASA is a highly soluble and highly permeable drug, leading to assignment of this active pharmaceutical ingredient (API) to Class I of the Biopharmaceutics Classification System (BCS). Limited bioequivalence (BE) studies reported in the literature indicate that products that have been tested are bioequivalent. Most of the excipients used in products with a marketing authorization in Europe are not considered to have an impact on gastrointestinal motility or permeability. Furthermore, ASA has a wide therapeutic index. Thus, the risks to the patient that might occur if a nonbioequivalent product were to be incorrectly deemed bioequivalent according to the biowaiver procedure appear to be minimal. As a result, the BCS-based biowaiver procedure can be recommended for approval of new formulations of solid oral dosage forms containing ASA as the only API, including both multisource and reformulated products, under the following conditions: (1) excipients are chosen from those used in ASA products already registered in International Conference on Harmonization and associated countries and (2) the dissolution profiles of the test and the comparator products comply with the BE guidance. PMID- 22674044 TI - Inhibiting Wipf2 downregulation by transgenic expression of its 3' mRNA untranslated region improves cytotoxicity and vaccination response. AB - Lymphocyte activation results in profound changes in the abundance of mRNA transcripts many of which are downregulated. The Wiskott-Aldrich syndrome (WAS) protein (WASP) family is critical for productive T-cell receptor signaling and actin reorganization. The WASP signal pathway includes the WAS/WAS-like (WASL) interacting protein family 2 (WIPF2) gene also known as WIRE/WICH. We show that both human WIPF2 and mouse Wipf2 are mice, alternatively spliced within the 3' untranslated region (3'UTR) resulting in two major transcripts of approximately 4.5 and 6 kb in size. Following T-cell activation, the level of human WIPF2 and mouse Wipf2 mRNA rapidly declines. In mice, this decline is accompanied by a marked reduction in WIPF2 protein levels. Transgenic expression of a 240-bp fragment derived from a highly conserved terminal 3'UTR found within the 6-kb transcript blocks Wipf2 downregulation. These effects may be mediated by competitive inhibition of microinhibitory RNA (miRNA) regulation since the 6-kb derived transgene and the 4.5-kb transcript share functional binding sites for miRNA146a. Blocking Wipf2 gene and protein repression resulted in improved T-cell responses to antigen immunization in vivo as well as in vitro cytotoxic T-cell killing. Collectively, these data suggest that early downregulation of this immunologically relevant gene controls the intensity of selective lymphocyte functions. PMID- 22674045 TI - Myoinjury transiently activates muscle antigen-specific CD8+ T cells in lymph nodes in a mouse model. AB - OBJECTIVE: To investigate the influence of myoinjury on antigen presentation to T cells in draining lymph nodes (LNs). METHODS: Muscle crush was performed in mice injected with exogenous ovalbumin (OVA) and in transgenic SM-OVA mice expressing OVA as a muscle-specific self antigen. Antigen exposure and the resulting stimulation of T cell proliferation in draining LNs was assessed by transferring carboxyfluorescein succinimidyl ester (CFSE)-labeled OVA-specific CD8+ and CD4+ T cells from OT-I and OT-II mice and by measuring the dilution of CFSE, which directly reflects their proliferation. The role of monocyte-derived dendritic cells (DCs) in T cell priming was assessed using pharmacologic blockade of DC migration. Immunofluorescence was used to detect CD8+ T cells, inflammatory monocyte-derived DCs, and type I major histocompatibility complex (MHC) expressing myofibers in crushed muscle, and to assess expression of perforin, interferon-gamma (IFNgamma), interleukin-2 (IL-2), IL-10, and transforming growth factor beta1 (TGFbeta1). RESULTS: OVA injection into intact muscle induced strong proliferation of CD4+ and CD8+ T cells, indicating efficient exposure of soluble antigens in draining LNs. OVA-specific CD8+ T cell proliferation in draining LNs of SM-OVA mice required myoinjury and was unaffected by pharmacologic inhibition of monocyte-derived DC migration. On day 7 postinjury, activated CD8+ T cells expressing perforin, IFNgamma and IL-2 were transiently detected in crushed muscle, and these cells were in close contact with class I MHC-positive regenerating myofibers. Beginning on day 7, the immunosuppressive cytokines IL-10 and TGFbeta1 were conspicuously expressed by CD11b+ cells, and CD8+ T cells rapidly disappeared from the healing muscle. CONCLUSION: Myofiber damage induces an episode of muscle antigen-specific CD8+ T cell proliferation in draining LNs. Activated CD8+ T cells transiently infiltrate the injured muscle, with prompt control by immunosuppressive cues. Inadequate control might favor sustained autoimmune myositis. PMID- 22674046 TI - MAGIC in practice: experience of peri-operative ECF/X chemotherapy in gastro esophageal adenocarcinomas. AB - BACKGROUND: The MAGIC trial demonstrated the perioperative regimen of Epirubicin (E), Cisplatin (C) and 5-Fluorouracil (F) to have an overall survival benefit for patients with gastro-esophageal adenocarcinomas. We present our experience of the peri-operative regimen of ECF/ECX(X = Capecitabine) in operable gastro-esophageal adenocarcinoma. METHODS: Analysis of retrospective data of patients treated with MAGIC style therapy between May 2006 and August 2008 with potentially operable gastro-esophageal adenocarcinoma. RESULTS: One hundred patients underwent peri operative chemotherapy according to the MAGIC protocol. Median age was 66 years, with 39% above the age of 70 years. The tumours were evenly distributed between the lower esophagus, gastro-esophageal junction and stomach. Seventy-nine percent completed all pre-operative cycles of chemotherapy and 81% proceeded to surgery, whilst 24% did not receive curative surgery. The median survival on an intention to treat analysis is 31.7 months from diagnosis. The median survival of patients who underwent resection has not yet been reached after a median follow-up of 41.4 months. CONCLUSION: Our patient population is older than the patients in the MAGIC trial (age 66 years vs. 62 years) with a much higher proportion of esophageal and GEJ tumours. Overall, curative resection rate was comparable to the MAGIC trial. Overall survival is superior to that found in the MAGIC trial. PMID- 22674048 TI - Dear readers of infection. PMID- 22674049 TI - Impact on the medical sector of revising the eye dose limit childhood cancer 2012 7th ICNIRP NIR workshop. PMID- 22674050 TI - Treatment outcome in older patients with childhood acute myeloid leukemia. AB - BACKGROUND: Older age has historically been an adverse prognostic factor in pediatric acute myeloid leukemia (AML). To the authors' knowledge, the impact of age relative to that of other prognostic factors on the outcome of patients treated in recent trials is unknown. METHODS: Clinical outcome and causes of treatment failure of 351 patients enrolled on 3 consecutive protocols for childhood AML between 1991 and 2008 were analyzed according to age and protocol. RESULTS: The more recent protocol (AML02) produced improved outcomes for patients aged 10 years to 21 years compared with 2 earlier studies (AML91 and AML97), with 3-year rates of event-free survival (EFS), overall survival (OS), and cumulative incidence of refractory leukemia or recurrence (CIR) for this group being similar to those of patients aged birth to 9 years: EFS: 58.3% +/- 5.4% versus 66.6% +/- 4.9% (P = .20); OS: 68.9% +/- 5.1% versus 75.1% +/- 4.5% (P = .36); and CIR: 21.9% +/- 4.4% versus 25.3% +/- 4.2% (P = .59). The EFS and OS estimates for patients aged 10 to 15 years overlapped those for patients aged 16 to 21 years. However, the cumulative incidence of toxic death was significantly higher for patients aged 10 to 21 years compared with younger patients (13.2% +/- 3.6% vs 4.5% +/- 2.0%; P = .028). CONCLUSIONS: The survival rate for older children with AML has improved on the results of a recent trial and is now similar to that of younger patients. However, deaths from toxicity remain a significant problem for patients in the older age group. Future trials should focus on improving supportive care while striving to develop more effective antileukemic therapy. PMID- 22674051 TI - Neuroprotective effect of endogenous pituitary adenylate cyclase-activating polypeptide on spinal cord injury. AB - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuroprotective peptide expressed in the central nervous system. To date, changes in the expression and effect of endogenous PACAP have not been clarified with respect to spinal cord injury (SCI). The aim of this study was to elucidate the expression pattern and function of endogenous PACAP on the contusion model of SCI using heterozygous PACAP knockout (PACAP(+/-)) and wild-type mice. Real-time polymerase chain reaction methods revealed that the level of PACAP mRNA increased gradually for 14 days after SCI and that PAC1R mRNA levels also increased for 7 days compared with intact control mice. PACAP and PAC1R immunoreactivities colabeled with a neuronal marker in the intact spinal cord. Seven days after SCI, PAC1R immunoreactivity was additionally co-expressed with an astrocyte marker. Wild type mice gradually recovered motor function after 14 days, but PACAP(+/-) mice showed significantly impaired recovery from 3 days compared with wild-type mice. The injury volume at day 7 in PACAP(+/-) mice, and the number of single-stranded DNA-immunopositive cells as a marker of neuronal cell death at day 3 were significantly higher than values measured in wild-type mice. These data suggest that endogenous PACAP is upregulated by SCI and has a neuroprotective effect on the damaged spinal cord. PMID- 22674052 TI - Fluoxetine upregulates phosphorylated-AKT and phosphorylated-ERK1/2 proteins in neural stem cells: evidence for a crosstalk between AKT and ERK1/2 pathways. AB - Fluoxetine is a widely used antidepressant drug which inhibits the reuptake of serotonin in the central nervous system (CNS). Recent studies have shown that fluoxetine can promote neurogenesis and improve the survival rate of neurons. However, whether fluoxetine modulates the neuroprotection of neural stem cells (NSCs) needs to be elucidated. In this study, we demonstrated that 50 MUM fluoxetine significantly upregulated expression of the phosphorylated-AKT and ERK1/2 proteins in NSCs derived from rats. Besides, expression of phosphorylated AKT and phosphorylated-ERK1/2 in fluoxetine-treated NSCs was effectively blocked (P<0.05) by both PI3-K inhibitor (LY294002) and MEK inhibitor (PD98059). It was, therefore, concluded that the crosstalk between PI3K/AKT and MAPK/ERK pathways involved AKT and ERK1/2 phosphorylation by fluoxetine treatment. This study points to a novel role of fluoxetine in neuroprotection as an antidepressant drug and also unravels the crosstalk mechanism between the two signaling pathways. PMID- 22674054 TI - Long-term outcomes of device closure of very large secundum atrial septal defects: a comparison of transcatheter vs intraoperative approaches. AB - BACKGROUND: Transcatheter device closure (TCDC) and intraoperative device closure (IODC) have emerged as minimally invasive methods in the treatment of secundum atrial septal defects (ASDs), but the long-term safety and efficacy remains uncertain for the large ASDs. HYPOTHESIS: TCDC may be as safe and efficacious as IODC for closure of large ASDs in terms of long-term clinical outcomes. METHODS: Ninety-two patients who had ASDs with a defect diameter of >=30 mm were included in this study. The patients received either TCDC (n = 42) or IODC (n = 50). An Amplatzer septal occluder was used in both groups. The dumbbell-like device deploying technique was introduced in the TCDC group. Physical exams, electrocardiography, and echocardiography were performed preprocedurally and postprocedurally at the index follow-up visits. RESULTS: The procedural immediate success rate was 97.6% for TCDC and 98.0% for IODC (P = 0.328). The rate of periprocedural complications was 9.5% for TCDC and 28.0% for IODC (P = 0.026). The mean hospital stay was 7.5 +/- 2.7 days for TCDC and 11.9 +/- 3.8 days for IODC (P < 0.001). For the mean follow-up of 5.4 +/- 0.5 years, there were no cardiac deaths and late complications in either group. No significant residual shunts were documented, and symptoms were significantly improved in both groups. Right and left ventricular diameter, pulmonary artery diameter, and pulmonary systolic pressure were all significantly decreased in both groups (P < 0.05). CONCLUSIONS: The present study confirmed the long-term safety and efficacy for closing a large ASD either by TCDC or IODC. Either of them could become an effective alternative to the surgery for large ASD closure. The authors have no funding, financial relationships, or conflicts of interest to disclose. PMID- 22674055 TI - Recombinant IgE antibody engineering to target EGFR. AB - Monoclonal antibodies have become a mainstay for the targeted treatment of cancer today. Some of the most successful targets of monoclonal antibodies are constituted by the epidermal growth factor receptor family spearheaded by the epidermal growth factor receptor (EGFR). Prompted by studies indicating that IgE compared to IgG may harness alternate effector functions to eradicate malignant cells, we addressed the establishment, engineering, and the potential tumoricidal effects of recombinant anti-EGFR IgE. Therefore, two different therapeutic EGFR specific antibodies, 225 and 425, were chosen for re-cloning into different chimeric IgE and IgG formats and produced in human cells. Simultaneous antibody binding to the sEGFR demonstrated accessibility of both epitopes for recombinant IgE. Proliferation and cytotoxicity assays demonstrated signal blocking and effector mediating capability of IgE isotypes. Pronounced degranulation in the presence of sEGFR upon activation exclusively with two IgE antibodies verified the epitope proximity and provides evidence that tumor-targeting by anti-EGFR IgE is safe with regard to soluble target structures. Degranulation mediated by tumor cells expressing EGFR could be demonstrated for singular and combined IgE antibodies; however, use of two IgE specificities was not superior to use of one IgE alone. The data suggest that the surface distribution of EGFR is optimally suited to mount a robust effector cell trigger and corroborate the potential and specificity of the IgE/IgE receptor network to react to xenobiotic or pathogenic patterns for targeting malignancies. PMID- 22674056 TI - Efficacy of adjuvant immunotherapy with cytokine-induced killer cells in patients with locally advanced gastric cancer. AB - PURPOSE: To determine the long-term efficacy of adjuvant immunotherapy with autologous cytokine-induced killer (CIK) cells for locally advanced gastric cancer patients. EXPERIMENTAL DESIGN: One hundred and fifty-one patients with stage III/IV gastric cancer who had undergone gastrectomy were enrolled, assigned to two groups (immunotherapy group versus no immunotherapy group/or control group), and followed. RESULTS: The 5-year overall survival (OS) and 5-year disease-free survival (DFS) rates for immunotherapy versus control group were 32.4 versus 23.4 % (P = 0.071) and 28.3 versus 10.4 % (P = 0.044), respectively. For patients with intestinal-type tumors, the 5-year OS and DFS rates were significantly higher for immunotherapy (OS, 46.8 vs. 31.4 % and P = 0.045; DFS, 42.4 vs. 15.7 % and P = 0.023). In the immunotherapy group, the mean CD3(+) level, CD4(+) level, and CD4(+)/CD8(+) ratio increased from 50.8, 26.5, and 0.9 %, respectively, at baseline to 62.6, 35.0, and 1.4 %, respectively, 1 week after the first CIK-cell treatment, returned to baseline after 2 months, and maintained a higher level (60.7 +/- 8.2 %, 34.2 +/- 7.1 %, and 1.3 +/- 0.3 %, respectively) 2 months after 3 cycles of immunotherapy. CONCLUSIONS: Adjuvant immunotherapy with CIK cells prolongs DFS in patients with locally advanced gastric cancer and significantly improves OS in patients with intestinal-type tumors. Intestinal type tumors could be selected as an important indication for CIK-cell therapy. This treatment may help improve T-lymphocyte subset distribution and improve the host's immune functions, but multiple cycles are necessary for long-term therapeutic efficacy. PMID- 22674058 TI - Using Screening for Distress, the sixth vital sign, to advance patient care with assessment and targeted interventions. PMID- 22674057 TI - Cellular and cytokine-dependent immunosuppressive mechanisms of grm1-transgenic murine melanoma. AB - Grm1-transgenic mice spontaneously develop cutaneous melanoma. This model allowed us to scrutinize the generic immune responses over the course of melanoma development. To this end, lymphocytes obtained from spleens, unrelated lymph nodes and tumor-draining lymph nodes of mice with no evidence of disease, and low or high tumor burden were analyzed ex vivo and in vitro. Thereby, we could demonstrate an increase in the number of activated CD4(+) and CD8(+) lymphocytes in the respective organs with increasing tumor burden. However, mainly CD4(+) T cells, which could constitute both T helper as well as immunosuppressive regulatory T cells, but not CD8(+) T cells, expressed activation markers upon in vitro stimulation when obtained from tumor-bearing mice. Interestingly, these cells from tumor-burdened animals were also functionally hampered in their proliferative response even when subjected to strong in vitro stimulation. Further analyses revealed that the increased frequency of regulatory T cells in tumor-bearing mice is an early event present in all lymphoid organs. Additionally, expression of the immunosuppressive cytokines TGF-beta1 and IL-10 became more evident with increased tumor burden. Notably, TGF-beta1 is strongly expressed in both the tumor and the tumor-draining lymph node, whereas IL-10 expression is more pronounced in the lymph node, suggesting a more complex regulation of IL-10. Thus, similar to the situation in melanoma patients, both cytokines as well as cellular immune escape mechanisms seem to contribute to the observed immunosuppressed state of tumor-bearing grm1-transgenic mice, suggesting that this model is suitable for preclinical testing of immunomodulatory therapeutics. PMID- 22674060 TI - An elegant access to formation and vaporization enthalpies of ionic liquids by indirect DSC experiment and "in silico" calculations. AB - We used DSC for determination of the reaction enthalpy of the synthesis of the ionic liquid [C(4)mim][Cl]. A combination of DSC and quantum chemical calculations presents a new, indirect way to study thermodynamics of ionic liquids. The new procedure was validated with two direct experimental measurements and MD simulations. PMID- 22674062 TI - Coagulation aggravates blood-induced joint damage in dogs. AB - OBJECTIVE: Joint bleeding due to trauma, major joint surgery, or hemophilia leads to joint damage. It is unclear if there are differences between coagulating blood and anticoagulated blood with respect to joint degeneration, especially in vivo. Therefore, we undertook this study to evaluate in a canine in vivo model whether intraarticular exposure to coagulating blood is more destructive than exposure to anticoagulated blood, and whether inflammation plays a role in the cartilage- damaging process. METHODS: In 7 dogs the left knees were injected with coagulating blood 4 times a week during weeks 1 and 4, and the right knees were injected with saline. In 7 other dogs, anticoagulated heparinized blood was injected, and heparinized saline was used as control. Ten weeks after the last injection, cartilage matrix turnover and synovial inflammation were analyzed. To study inflammation-independent cartilage damage, explants of cartilage from at least 6 human donors per group were exposed in vitro to coagulating and anticoagulated blood, plasma, and serum for 4 days. Cartilage matrix turnover was determined after a recovery period of 12 days. RESULTS: Canine knees injected with coagulating blood showed more disturbed proteoglycan turnover than knees injected with anticoagulated blood. Synovial inflammation was present only after intraarticular injections with coagulating blood. In in vitro experiments, exposure of human cartilage explants to coagulating blood resulted in more damage than did exposure to anticoagulated blood, while exposure to plasma and serum did not alter cartilage matrix turnover. CONCLUSION: This study shows that coagulating blood causes more long-lasting in vivo joint damage than anticoagulated blood, thereby suggesting that along with joint bleeding in hemophilia, exposure to intraarticular blood should also be avoided during surgery and trauma to prevent joint damage. PMID- 22674063 TI - Organic molecules on the surface of water droplets--an energetic perspective. AB - The solubility of organic molecules is a well established property, founded on decades of measurements, the results of which have been tabulated in handbooks. Under atmospheric conditions water droplets may form containing small amounts of other molecules. Such droplets typically have a very large area to volume ratio, which may shift the solvation equilibrium towards molecules residing on the droplet surface. The presence of organic molecules on droplet surfaces is extremely important for reactivity--it is well established that certain chemical reactions are more prevalent under atmospheric conditions than in bulk. Here we present a thermodynamic rationalization of the surface solvation properties of methanol, ethanol, propanoic acid, n-butylamine, diethyl ether, and neopentane based on potential of mean force (PMF) calculations--we have previously demonstrated that an energetic description is a very powerful means of disentangling the factors governing solvation (Caleman et al., Proc. Natl. Acad. Sci. U. S. A., 2011, 108, 6838-6842). All organic molecules investigated here are preferentially solvated on the surface of the droplets rather than in the inside, yet the magnitude of surface preference may differ by orders of magnitude. In order to dissect the energetic contributions that govern surface preference, we decompose the PMF into enthalpic and entropic components, and, in a second step, into contributions from water-water and solute-water interactions. The analysis demonstrates that surface preference is primarily an enthalpic effect, but the magnitude of surface preference of solutes containing large apolar groups is enhanced due to entropy. We introduce an analysis of the droplet PMFs that allows one to extrapolate the results to larger droplets. From this we can estimate the solubility of the solutes in water droplets, demonstrating that the solubility in droplets can be orders of magnitude larger than in bulk water. Our findings have implications for understanding the process of electrospray ionization, an important technique in biological mass spectrometry, since our work strongly suggests that in equilibrium biomolecules would be adsorbed on the droplet surface as well. PMID- 22674064 TI - Effects of substrate concentrations on performance of serially connected microbial fuel cells (MFCs) operated in a continuous mode. AB - Stacking of microbial fuel cells (MFC) by connecting multiple small-sized units in a series is used for generating higher power from the MFCs. However, voltage reversal is a critical problem in a serially connected MFC unit. The voltage reversal often occurs when substrate concentration is relatively low in the anodic compartment. Two rectangular individual cells were stacked together in series: MFC1 was fed with 1 g glucose L(-1) throughout the experiment while MFC2 was fed with various concentrations of glucose (0.1, 0.2, 0.3, 0.5 and 0.8 g L( 1)). Voltage reversal occurred when the stack configuration was performed using (1 + 0.1) g glucose L(-1). The stacked configurations with (1 + 0.2, 1 + 0.3, 1 + 0.5 and 1 + 0.8) g glucose L(-1) were operated successfully without the voltage reversal. The maximum powers of 1.88, 2.04, 3.6, 2.5 and 2.18 mW were obtained with the stacked configurations of (1 + 0.2), (1 + 0.3), (1 + 0.5), (1 + 0.8) and (1 + 1) g glucose L(-1), respectively. Except in the stacked configuration with (1 + 0.1) g glucose L(-1), the stacked voltages obtained were similar. PMID- 22674061 TI - A dicarboxylic fatty acid derivative of paclitaxel for albumin-assisted drug delivery. AB - Paclitaxel (PTX) is a potent chemotherapy for many cancers but it suffers from very poor solubility. Consequently, the TAXOL formulation uses copious amounts of the surfactant Cremophor EL to solubilize the drug for injection, resulting in severe hypersensitivity and neutropenia. In contrast to Cremophor EL, presented is a way to solubilize PTX by conjugation of a dicarboxylic fatty acid for specific binding to the ubiquitous protein, serum albumin. The conjugation chemistry was simplified to a single step using the activated anhydride form of 3 pentadecylglutaric (PDG) acid, which is reactive to a variety of nucleophiles. The PDG derivative is less cytotoxic than the parent compound and was found to slowly hydrolyze to PTX (~ 5% over 72 h) in serum, tumor cytosol, and tumor tissue homogenate. When injected intravenously to tumor-bearing mice, [(3) H]-PTX in the TAXOL formulation was cleared rapidly with a half-life of 7 h. In the case of the PDG derivative of PTX, the drug is quickly distributed and approximately 20% of the injected dose remained in the vasculature experiencing a 23 h half life. These improvements from modifying PTX with the PDG fatty acid present the opportunity for PDG to become a generic modification for the improvement of many therapeutics. PMID- 22674065 TI - An introduction to adherens junctions: from molecular mechanisms to tissue development and disease. AB - Adherens junctions (AJs) are fundamental for the development of animal tissues and organs. The core complex is formed from transmembrane cell-cell adhesion molecules, cadherins, and adaptor molecules, the catenins, that link to cytoskeletal and regulatory networks within the cell. This complex can be considered over a wide range of biological organization, from atoms to molecules, protein complexes, molecular networks, cells, tissues, and overall animal development. AJs have also been an integral part of animal evolution, and play central roles in cancer development and pathogen infection. This book addresses major questions encompassing these aspects of AJ biology. How did AJs evolve? How do the cadherins and catenins interact to assemble AJs and mediate adhesion? How do AJs interface with other cellular machinery to couple adhesion with the whole cell? How do AJs affect cell behaviour and multicellular development? How can abnormal AJ activity lead to disease? PMID- 22674066 TI - Evolution of the cadherin-catenin complex. AB - Adherens junctions are the most common junction type found in animal epithelia. Their core components are classical cadherins and catenins, which form membrane spanning complexes that mediate intercellular binding on the extracellular side and associate with the actin cytoskeleton on the intracellular side. Junctional cadherin-catenin complexes are key elements involved in driving animal morphogenesis. Despite their ubiquity and importance, comparative studies of classical cadherins, catenins and their related molecules suggest that the cadherin/catenin-based adherens junctions have undergone structural and compositional transitions during the diversification of animal lineages. This chapter describes the molecular diversities related to the cadherin-catenin complex, based on accumulated molecular and genomic information. Understanding when and how the junctional cadherin-catenin complex originated, and its subsequent diversification in animals, promotes a comprehensive understanding of the mechanisms of animal morphological diversification. PMID- 22674067 TI - The three-dimensional structure of the cadherin-catenin complex. AB - The cadherin-catenin complex is the major building block of the adherens junction. It is responsible for coupling Ca(2+)-dependent intercellular junctions with various intracellular events, including actin dynamics and signaling pathways. Determination of three-dimensional structures of cadherins, p120 catenin, beta-catenin and alpha-catenin at atomic-level resolution has allowed us to examine how the structure and function of cell adhesion molecules are further modulated by protein-protein interactions. Structural studies of cadherins revealed the strand-swap-dependent and -independent trans-dimerization mechanisms, as well as a potential mechanism for lateral clustering of cadherin trans-dimers. Crystallographic and NMR analyses of p120 catenin revealed that it regulates the stability of cadherin-mediated cell-cell adhesion by associating with the majority of the E-cadherin juxtamembrane domain, including residues implicated in clathrin-mediated endocytosis and Hakai-dependent ubiquitination. Crystal structures of the beta-catenin/E-cadherin complex and the beta-/alpha catenin chimera revealed extensive interactions necessary to form the cadherin/beta-catenin/alpha-catenin ternary complex. Structural characterization of alpha-catenin has revealed conformational changes within the N-terminal and modulatory domains that are crucial for its role as a mechanosensor of cell-cell adhesion. Further insights into the connection between the cadherin-catenin complex and the actin cytoskeleton are integral to better understand how adjoining cells communicate through cell-cell adhesion. PMID- 22674068 TI - Biophysics of cadherin adhesion. AB - Since the identification of cadherins and the publication of the first crystal structures, the mechanism of cadherin adhesion, and the underlying structural basis have been studied with a number of different experimental techniques, different classical cadherin subtypes, and cadherin fragments. Earlier studies based on biophysical measurements and structure determinations resulted in seemingly contradictory findings regarding cadherin adhesion. However, recent experimental data increasingly reveal parallels between structures, solution binding data, and adhesion-based biophysical measurements that are beginning to both reconcile apparent differences and generate a more comprehensive model of cadherin-mediated cell adhesion. This chapter summarizes the functional, structural, and biophysical findings relevant to cadherin junction assembly and adhesion. We emphasize emerging parallels between findings obtained with different experimental approaches. Although none of the current models accounts for all of the available experimental and structural data, this chapter discusses possible origins of apparent discrepancies, highlights remaining gaps in current knowledge, and proposes challenges for further study. PMID- 22674069 TI - Adherens junction assembly. AB - Classical cadherins are a family of transmembrane proteins that mediate cell-cell adhesion at adherens junctions. A complex chain of cis- and trans- interactions between cadherin ectodomains establishes a cadherin adhesive cluster. A principal adhesive interaction in such clusters is an exchange of beta strands between the first extracellular cadherin domains (EC1). The structure of cadherin adhesive clusters can be modified by other adherens junction proteins including additional transmembrane proteins, nectins and various intracellular proteins that directly or indirectly interact with the intracellular cadherin region. These interactions determine the dynamics and stability of cadherin adhesive structures. PMID- 22674070 TI - The cytoskeleton and classical cadherin adhesions. AB - This chapter discusses the biochemical and functional links between classical cadherin adhesion systems and the cytoskeleton. Cadherins are best understood to cooperate with the actin cytoskeleton, but there is increasing evidence for the role of junctional microtubules in regulating cadherin biology. Cadherin adhesions and the junctional cytoskeleton are both highly dynamic systems that undergo continual assembly, turnover and remodeling, and yet maintain steady state structures necessary for intercellular adhesion. This requires the functional coordination of cadherins and cadherin-binding proteins, actin regulatory proteins, organizers of microtubule assembly and structure, and signaling pathways. These components act in concert to regulate junctional organization in response to extracellular forces and changing cellular contexts, which is essential for intercellular cohesion and tissue integrity. PMID- 22674071 TI - Immunoglobulin superfamily receptors and adherens junctions. AB - The immunogroblin (Ig) superfamily proteins characterized by the presence of Ig like domains are involved in various cellular functions. The properties of the Ig like domains to form rod-like structures and to bind specifically to other proteins make them ideal for cell surface receptors and cell adhesion molecules (CAMs). Ig-CAMs, nectins in mammals and Echinoid in Drosophila, are crucial components of cadherin-based adherens junctions in the epithelium. Nectins form cell-cell adhesion by their trans-interactions and recruit cadherins to the nectin-initiated cell-cell adhesion site to establish adherens junctions. Thereafter junction adhesion molecules, occludin, and claudins, are recruited to the apical side of adherens junctions to establish tight junctions. The recruitment of these molecules by nectins is mediated both by the direct and indirect interactions of afadin with many proteins, such as catenins, and zonula occludens proteins, and by the nectin-induced reorganization of the actin cytoskeleton. Nectins contribute to the formation of both homotypic and heterotypic types of cell-cell junctions, such as synapses in the brain, contacts between pigment and non-pigment cell layers of the ciliary epithelium in the eye, Sertoli cell-spermatid junctions in the testis, and sensory cells and supporting cells in the sensory organs. In addition, cis- and trans-interactions of nectins with various cell surface proteins, such as integrins, growth factor receptors, and nectin-like molecules (Necls) play important roles in the regulation of many cellular functions, such as cell polarization, movement, proliferation, differentiation, survival, and cell sorting. Furthermore, the Ig-CAMs are implicated in many human diseases including viral infections, ectodermal dysplasia, cancers, and Alzheimer's disease. PMID- 22674074 TI - Adherens junctions during cell migration. AB - Migration is a key cellular process, involved during morphogenetic movements as well as in the adult where it participates in immune cell trafficking, wound healing or tumour invasion. As they migrate, cells interact with a microenvironment composed of extracellular matrix and neighbouring cells. Cell cell adhesions ensure tissue integrity while they allow migration of single or grouped cells within this tissue. Cadherin and nectin-based adherens junctions are key players in intercellular interactions. They are used as adhesive complexes whose mechanical properties improve cell coordination during collective migration and promote cell motility on cadherin substrates. In addition, adherens junctions transduce signals that actively participate in the control of directed cell migration, by providing polarity cues and also participating in contact inhibition of motility. PMID- 22674072 TI - Signaling from the adherens junction. AB - The cadherin/catenin complex organizes to form a structural Velcro that joins the cytoskeletal networks of adjacent cells. Functional loss of this complex arrests the development of normal tissue organization, and years of research have gone into teasing out how the physical structure of adhesions conveys information to the cell interior. Evidence that most cadherin-binding partners also localize to the nucleus to regulate transcription supports the view that cadherins serve as simple stoichiometric inhibitors of nuclear signals. However, it is also clear that cadherin-based adhesion initiates a variety of molecular events that can ultimately impact nuclear signaling. This chapter discusses these two modes of cadherin signaling in the context of tissue growth and differentiation. PMID- 22674075 TI - Adherens junctions and cadherins in Drosophila development. AB - Drosophila represents a paradigm for the analysis of the cellular, molecular and genetic mechanisms of development and is an ideal model system to study the contribution of Adherens Junctions (AJs) and their major components, cadherins, to morphogenesis. The combination of different techniques and approaches has allowed researchers to identify the requirements of these epithelial junctions in vivo in the context of a whole organism. The functional analysis of mutants for AJ core components, particularly for Drosophila DE-cadherin, has shown that AJs play critical roles in virtually all stages of development. For instance, AJs maintain tissue integrity while allowing the remodelling and homeostasis of many tissues. They control cell shape, contribute to cell polarity, facilitate cell cell recognition during cell sorting, orient cell divisions, or regulate cell rearrangements, among other activities. Remarkably, these activities require a very fine control of the organisation and turnover of AJs during development. In addition, AJs engage in diverse and complex interactions with the cytoskeleton, signalling networks, intracellular trafficking machinery or polarity cues to perform these functions. Here, by summarising the requirements of AJs and cadherins during Drosophila morphogenesis, we illustrate the capital contribution of this model system to our knowledge of the mechanisms and biology of AJs. PMID- 22674073 TI - Adherens junction turnover: regulating adhesion through cadherin endocytosis, degradation, and recycling. AB - Adherens junctions are important mediators of intercellular adhesion, but they are not static structures. They are regularly formed, broken, and rearranged in a variety of situations, requiring changes in the amount of cadherins, the main adhesion molecule in adherens junctions, present at the cell surface. Thus, endocytosis, degradation, and recycling of cadherins are crucial for dynamic regulation of adherens junctions and control of intercellular adhesion. In this chapter, we review the involvement of cadherin endocytosis in development and disease. We discuss the various endocytic pathways available to cadherins, the adaptors involved, and the sorting of internalized cadherin for recycling or lysosomal degradation. In addition, we review the regulatory pathways controlling cadherin endocytosis and degradation, including regulation of cadherin endocytosis by catenins, cadherin ubiquitination, and growth factor receptor signaling pathways. Lastly, we discuss the proteolytic cleavage of cadherins at the plasma membrane. PMID- 22674077 TI - Cadherin function during Xenopus gastrulation. AB - Xenopus gastrulation consists of the orderly deformation of a single, multilayered cell sheet that resembles a multilayered epithelium, and flexible cell-cell adhesion has to provide tissue cohesion while allowing for cell rearrangements that drive gastrulation. A few classic cadherins are expressed in the Xenopus early embryo. The prominent C-cadherin is essential for the cohesion of the animal part of the gastrula including ectoderm and chordamesoderm, and it contributes to the adhesion of endoderm and anterior mesoderm in the vegetal moiety. The cadherin/catenin complex is expressed in a graded pattern which is stable during early development. Regional differences in cell adhesion conform to the graded cadherin/catenin expression pattern. However, although the cadherin/catenin pattern seems to be actively maintained, and cadherin function is modulated to reinforce differential adhesiveness, it is not clear how regional differences in tissue cohesion affect gastrulation. Manipulating cadherin expression or function does not induce cell sorting or boundary formation in the embryo. Moreover, known boundary formation mechanisms in the gastrula are based on active cell repulsion. Cell rearrangement is also compatible with variable tissue cohesion. Thus, identifying roles for differential adhesion in the Xenopus gastrula remains a challenge. PMID- 22674078 TI - Adherens junctions in mammalian development, homeostasis and disease: lessons from mice. AB - Mice have proven to be a particularly powerful model to study molecular mechanisms of development and disease. The reason for this is the close evolutionary relationship between rodents and humans, similarities in physiological mechanisms in mice and human, and the large number of techniques available to study gene functions in mice. A large number of mice mutations, either germ line, conditional or inducible, have been generated in the past years for adherens junctions components, and the number is still increasing. In this review we will discuss mice models that have contributed to understanding the developmental and physiological role of adherens junctions and their components in mammals and have revealed novel mechanistic aspects of how adherens junctions regulate morphogenesis and tissue homeostasis. PMID- 22674076 TI - Adherens junctions in C. elegans embryonic morphogenesis. AB - Caenorhabditis elegans provides a simplified, in vivo model system in which to study adherens junctions (AJs) and their role in morphogenesis. The core AJ components-HMR-1/E-cadherin, HMP-2/beta-catenin and HMP-1/alpha-catenin-were initially identified through genetic screens for mutants with body axis elongation defects. In early embryos, AJ proteins are found at sites of contact between blastomeres, and in epithelial cells AJ proteins localize to the multifaceted apical junction (CeAJ)-a single structure that combines the adhesive and barrier functions of vertebrate adherens and tight junctions. The apically localized polarity proteins PAR-3 and PAR-6 mediate formation and maturation of junctions, while the basolaterally localized regulator LET-413/Scribble ensures that junctions remain apically positioned. AJs promote robust adhesion between epithelial cells and provide mechanical resistance for the physical strains of morphogenesis. However, in contrast to vertebrates, C. elegans AJ proteins are not essential for general cell adhesion or for epithelial cell polarization. A combination of conserved and novel proteins localizes to the CeAJ and works together with AJ proteins to mediate adhesion. PMID- 22674079 TI - Adherens junctions and stem cells. AB - The specification, maintenance, division and differentiation of stem cells are integral to the development and homeostasis of many tissues. These stem cells often live in specialized anatomical areas, called niches. While niches can be complex, most involve cell-cell interactions that are mediated by adherens junctions. A diverse array of functions have been attributed to adherens junctions in stem cell biology. These include physical anchoring to the niche, control of proliferation and division orientation, regulation of signaling cascades and of differentiation. In this review, a number of model stem cell systems that highlight various functions of adherens junctions are discussed. In addition, a summary of the current understanding of adherens junction function in mammalian tissues and embryonic and induced pluripotent stem cells is provided. This analysis demonstrates that the roles of adherens junctions are surprisingly varied and integrated with both the anatomy and the physiology of the tissue. PMID- 22674080 TI - Adherens junctions and cancer. AB - Cadherins and catenins are the central cell-cell adhesion molecules in adherens junctions (AJs). This chapter reviews the knowledge concerning the role of cadherins and catenins in epithelial cancer and examines the published literature demonstrating the changes in the expression and function of these proteins in human cancer and the association of these changes with patient outcomes. The chapter also covers the mechanistic studies aiming at uncovering the significance of changes in cadherin and catenin expression in cancer and potential molecular mechanisms responsible for the causal role of AJs in cancer initiation and progression. PMID- 22674081 TI - Adherens junctions and pathogen entry. AB - Epithelia are highly organised structures protecting underlying tissues against microbial pathogens. Epithelial morphogenesis and maintenance is mediated by cell cell adhesion molecules organised in junctional complexes, such as the adherens junctions. The tight organisation of these complexes and their interactions with cellular factors render the epithelia impermeable to potential invaders. Nevertheless, pathogens have developed strategies to target, interact and manipulate junctional complexes, in order to disrupt or cross the epithelial barriers and cause infection. Bacteria, viruses and parasites access the junctional molecular components either directly, often taking advantage of physiological alterations in epithelial polarity, or indirectly, by delivering into cells molecular factors that destabilise junctional integrity. Importantly, microbial interactions with junctional components are instrumental not only to elucidate mechanisms of invasion, but also to unravel fundamental physiological properties of the epithelial barriers, at the cellular and tissular level. PMID- 22674082 TI - Brief Report: IRF5 systemic lupus erythematosus risk haplotype is associated with asymptomatic serologic autoimmunity and progression to clinical autoimmunity in mothers of children with neonatal lupus. AB - OBJECTIVE: Variation in the interferon regulatory factor 5 (IRF5) gene has been associated with risk of developing systemic lupus erythematosus (SLE), and this association is largely dependent upon anti-Ro autoantibodies. This study was undertaken to determine if the IRF5 genotype is associated with maternal diagnosis or progression of autoimmunity. METHODS: Genotyping of haplotype tagging polymorphisms in IRF5 was performed in 93 subjects of European ancestry who were recruited to the Research Registry for Neonatal Lupus. All subjects had high-titer anti-Ro autoantibodies and had a child with neonatal lupus (NL); allele frequencies were compared to those in nonautoimmune controls. The mothers had SLE, Sjogren's syndrome (SS), or undifferentiated autoimmune syndrome (UAS), or were asymptomatic. RESULTS: The SLE risk haplotype of IRF5 was enriched in all anti-Ro-positive subjects except in those with SS (odds ratio [OR] 2.55, P = 8.8 * 10(-4) ). The SLE risk haplotype was even enriched in asymptomatic individuals with anti-Ro antibodies (OR 2.69, P = 0.019). The same haplotype was more prevalent in subjects who were initially asymptomatic but developed symptomatic SLE during followup (OR 5.83, P = 0.0024). Interestingly, SS was associated with 2 minor IRF5 haplotypes, and these same haplotypes were decreased in frequency in mothers with SLE and those with UAS. CONCLUSION: The IRF5 SLE risk haplotype was associated with anti-Ro antibody positivity in asymptomatic individuals, as well as with progression to SLE in asymptomatic anti-Ro-positive individuals. SS in mothers of children with NL was associated with different IRF5 haplotypes. These data suggest that IRF5 polymorphisms play a role in serologic autoimmunity in humans and may promote the progression to clinical autoimmunity. PMID- 22674083 TI - Cyclooxygenase-independent neuroprotective effects of aspirin against dopamine quinone-induced neurotoxicity. AB - Prostaglandin H synthase exerts not only cyclooxygenase activity but also peroxidase activity. The latter activity of the enzyme is thought to couple with oxidation of dopamine to dopamine quinone. Therefore, it has been proposed that cyclooxygenase inhibitors could suppress dopamine quinone formation. In the present study, we examined effects of various cyclooxygenase inhibitors against excess methyl L-3,4-dihydroxyphenylalanine (L-DOPA)-induced quinoprotein (protein bound quinone) formation and neurotoxicity using dopaminergic CATH.a cells. The treatment with aspirin inhibited excess methyl L-DOPA-induced quinoprotein formation and cell death. However, acetaminophen did not show protective effects, and indomethacin and meloxicam rather aggravated these methyl L-DOPA-induced changes. Aspirin and indomethacin did not affect the level of glutathione that exerts quenching dopamine quinone in dopaminergic cells. In contrast with inhibiting effects of higher dose in the previous reports, relatively lower dose of aspirin that affected methyl L-DOPA-induced quinoprotein formation and cell death failed to prevent cyclooxygenase-induced dopamine chrome generation in cell free system. Furthermore, aspirin but not acetaminophen or meloxicam showed direct dopamine quinone-scavenging effects in dopamine-semiquinone generating systems. The present results suggest that cyclooxygenase shows little contribution to dopamine oxidation in dopaminergic cells and that protective effects of aspirin against methyl L-DOPA-induced dopamine quinone neurotoxicity are based on its cyclooxygenase-independent property. PMID- 22674084 TI - Assessment of oxidative parameters in rat spinal cord after chronic constriction of the sciatic nerve. AB - Although reactive oxygen species (ROS) are involved in neuropathic pain, the direct relationship between these species and chronic constriction of sciatic nerve (CCI) has not been studied in spinal cord. Thus, this study induced CCI in rats and these animals were sacrificed 3 and 10 days after the surgical procedure to determine the superoxide dismutase (SOD) and catalase activities, as well as ascorbic acid, hydrogen peroxide (H(2)O(2)) and lipid hydroperoxide levels in lumbosacral spinal cord. Von Frey Hair and hot plate tests were performed to assess the degree of mechanical and thermal hyperalgesia at days 0, 3 and 10. The results showed that CCI significantly induced mechanical and thermal hyperalgesia at days 3 and 10. Parallel there was increase in spinal cord lipid hydroperoxide at days 3 and 10 in rats submitted to CCI. In Sham rats a significant increase in this parameter occurred at day 10. H(2)O(2) decreased at day 10 only in CCI group. SOD activity was decreased in Sham and CCI groups at day 3, while catalase activity was increased in CCI rats at days 3 and 10. Ascorbic acid levels were reduced only in CCI rats at day 3. Although the role of such changes is unclear, many were not specific to neuropathic pain and the differences could be related to different degrees of central sensitization in Sham and CCI rats. PMID- 22674085 TI - Cooperation of non-effective concentration of glutamatergic system modulators and antioxidant against oxidative stress induced by quinolinic acid. AB - Excessive formation of reactive oxygen species (ROS) and disruption of glutamate uptake have been hypothesized as key mechanisms contributing to quinolinic acid (QA)-induced toxicity. Thus, here we investigate if the use of diphenyl diselenide (PhSe)(2), guanosine (GUO) and MK-801, alone or in combination, could protect rat brain slices from QA-induced toxicity. QA (1 mM) increased ROS formation, thiobarbituric acid reactive substances (TBARS) and decreased cell viability after 2 h of exposure. (PhSe)(2) (1 MUM) protected against this ROS formation in the cortex and the striatum and also prevented decreases in cell viability induced by QA. (PhSe)(2) (5 MUM) prevented ROS formation in the hippocampus. GUO (10 and 100 MUM) blocked the increase in ROS formation caused by QA and MK-801 (20 and 100 MUM) abolished the pro-oxidant effect of QA. When the noneffective concentrations were used in combination produced a decrease in ROS formation, mainly (PhSe)(2) + GUO and (PhSe)(2) + GUO + MK-801. These results demonstrate that this combination could be effective to avoid toxic effects caused by high concentrations of QA. Furthermore, the data obtained in the ROS formation and cellular viability assays suggest different pathways in amelioration of QA toxicity present in the neurodegenerative process. PMID- 22674086 TI - The development of IL-17/IFN-gamma-double producing CTLs from Tc17 cells is driven by epigenetic suppression of Socs3 gene promoter. AB - The plasticity of T lymphocytes induced by epigenetic modifications of gene promoters may play a pivotal role in controlling their effector functions, which are sometimes causally associated with immune disorders. IL -17-producing T cells, which induce type 17 immune responses, are newly identified pathogenic effector cells. The type 1 signature cytokine IFN-gamma strongly inhibits their differentiation, indicating a mutually exclusive relationship between type 17- and type 1-immune responses. However, many reports indicate the presence of a unique IL-17/IFN-gamma-double producing T-cell subset in various inflammatory settings, although the mechanisms responsible for their development and their precise functions remain unclear. Here, we demonstrate that IL-12 permits the conversion of mouse IL-17-producing CD8(+) T (Tc17) cells to IL-17/IFN-gamma double producing CD8(+) T (Tc17/IFN-gamma) cells, and that this conversion is due to repressive epigenetic modifications of Socs3 gene promoters. Moreover, we show that SOCS3 strongly regulates the capability of Tc17 cells to produce IL-17, in addition to regulating the expression of the type 17-master regulator RORgammat. These findings elucidate the mechanisms underlying the conversion of Tc17 cells into Tc17/IFN-gamma cells. As these cells are known to have potent antitumor activities, manipulation of these conversion mechanisms for therapeutic tumor immunity may be possible. PMID- 22674089 TI - Early steroid withdrawal regimen prevents new-onset diabetes mellitus in old-age recipients after living donor liver transplantation. AB - BACKGROUND: Steroid use after liver transplantation is known to increase the risk of new-onset diabetes mellitus (NODM). In this study, we tried to identify a patient subgroup who would benefit with regard to NODM by an early steroid withdrawal regimen (ESWR) after living donor liver transplantation (LDLT) METHODS: Among 100 adult LDLT patients, 65 were on a conventional immunosuppressive regimen (CIR), and 35 were on an ESWR. With the ESWR, the steroid was tapered off mostly within 7 days with induction of basiliximab in combination with tacrolimus and mycophenolate mofetil (MMF). The CIR was a combination of tacrolimus and steroid. MMF was added in selected patients. Steroid was tapered off 2-6 months after LT. The presence of NODM was investigated cross-sectionally 6 months after LT. RESULTS: There was no significant difference in terms of acute cellular rejection, sepsis, or death during follow-up. NODM had developed in 13 patients (13 %). Old recipient age (>= 55) and pretransplant history of hypertension were significant risk factors for NODM. The type of immunosuppression was the single risk factor for NODM in subgroup of old-age recipients (>= 55 years) on the CIR (hazard ratio 13.34, p = 0.04). CONCLUSIONS: ESWR can safely reduce the incidence of NODM after LDLT in old-age recipients. Therefore, ESWR should be considered first in old-age recipients undergoing LDLT. PMID- 22674090 TI - A new classification of positive sestamibi and ultrasound scans in parathyroid localization. AB - BACKGROUND: Ultrasound (US) and sestamibi (MIBI) are traditionally considered positive or negative. The purpose of this study was to define and test a new scoring system for MIBI and US and to determine whether this can improve their accuracy for primary hyperparathyroidism. METHODS: This is a prospective study of 200 consecutive patients with primary hyperparathyroidism who had a single uptake on MIBI scans before bilateral neck exploration at a tertiary academic center between 2007 and 2008. These patients also had surgeon-performed neck US in the office, which was scored as "typical" or "atypical" based on how characteristic the image resembled a parathyroid gland. The MIBI uptake was scored by the nuclear medicine specialist as "weak," "moderate," or "strong" compared with the signal intensity of the thyroid. US and MIBI scoring was done preoperatively and their findings were compared with operative data. RESULTS: Of 200 patients, 71 % had a single adenoma, 12 % had double adenomas, and 17 % had four-gland hyperplasia. A weak, moderate, and strong signal on MIBI had an accuracy of 23, 47, and 72 %, respectively, in demonstrating single-gland disease. An atypical versus typical US appearance was accurate in 55 and 74 % of the time, in identifying single-gland disease. CONCLUSIONS: An appraisal of US and MIBI positivity in relation to image characteristics affects the reliability of both studies. This information should be kept in mind when selecting patients for focal neck exploration. PMID- 22674091 TI - Strengthening surgical services at the soum (first-referral) hospital: the WHO emergency and essential surgical care (EESC) program in Mongolia. AB - BACKGROUND: Provision of surgical care continues to receive little attention and funding despite the growing burden of surgical disease worldwide. In 2004, The World Health Organization (WHO) established the Emergency and Essential Surgical Care (EESC) program, which was designed to strengthen surgical services at the first-referral hospital. There are limited data documenting the implementation and scale-up of such services. We describe the nationwide implementation of the EESC program in Mongolia over a 6 year period. METHODS: Surgical services were increased in rural areas of Mongolia using the WHO Integrated Management of Emergency and Essential Surgical Care (IMEESC) toolkit from 2004 to 2010. Fund of knowledge tests and program evaluation was done to measure uptake, response, and perceived importance of the program. Two years after the pilot sites were launched, programmatic impact on short-term process measures was evaluated using the WHO Monitoring and Evaluation form. RESULTS: The program was implemented in 14 aimags/provinces (66.67 %) and 178 soum hospitals (52.66 %). Fund of knowledge scores increased from 47.72 % (95 % confidence interval (CI) 40.7-54.7) to 77.9 % (95 % CI 70.1-85.7, p = 0.0001) after the training program. 1 year post-training, there was a 57.1 % increase in the availability of emergency rooms, 59.1 % increase in the supply of emergency kits, a 73.64 % increase in the recording of emergency care cases, and a 46.66 % increase in the provision of facility and instrument usage instructions at the pilot sites. CONCLUSIONS: The EESC program was successfully implemented and scaled up at a national level with improvements in short-term process measures. PMID- 22674092 TI - Laparoscopic total gastrectomy with D2 lymphadenectomy for advanced gastric cancer. AB - BACKGROUND: The use of laparoscopic total gastrectomy (LTG) for the treatment of advanced gastric cancer (AGC) has not yet gained widespread acceptance because of difficulties in performing D2 lymphadenectomy. The purpose of this study was to evaluate the safety and effectiveness of LTG with D2 lymphadenectomy in treating AGC. METHODS: A total of 94 patients who underwent LTG with D2 lymphadenectomy for AGC between January 2005 and October 2011 were included in this study. The patient data were obtained from a prospectively maintained institutional database. Morbidity was stratified by the Clavien-Dindo classification. RESULTS: Concurrent pancreatectomy or splenectomy was performed on 48 patients. The median operation time was 230 min, and the median number of lymph nodes harvested per patient was 60.5. The TNM stages of the tumor were Ib in 9 patients (9.6 %), IIa in 16 (17 %), IIb in 7 (7.4 %), IIIa in 16 (17 %), IIIb in 17 (18.1 %), IIIc in 25 (26.6 %), and IV in 4 (4.3 %). Major morbidity (>= grade IIIa) occurred in 9 patients (9.6 %) without postoperative mortality. At last follow-up, tumor recurrence had occurred in 13 patients with a median follow-up time of 12.77 months. CONCLUSIONS: The acceptable rate of major morbidity in our series suggested that laparoscopic total gastrectomy with D2 lymphadenectomy is applicable to AGC. Long-term follow-up is mandatory to validate long-term outcome. PMID- 22674093 TI - Key performance indicators in an acute surgical unit: have we made an impact? AB - INTRODUCTION: Timely access to acute surgery is a worldwide issue and New Zealand is similarly affected. Auckland City Hospital is one of the largest metropolitan public hospitals in New Zealand where more than 60 % of surgical admissions fit into the acute category. In January 2009, an Acute Surgical Unit (ASU) was set up to improve acute surgical flow. Key performance indicators (KPIs) were identified as valuable tools in evaluating ASU service performance. Our goals were to describe the current acute patient pathway, present the early trend of KPIs for the ASU and determine whether an impact has been made on acute surgical patients. METHODS: A retrospective review of patients admitted with acute general surgical conditions from January 2008 (pre-ASU) to October 2010 was performed. Patient data were identified through hospital electronic records. KPIs assessed included: (1) time to assess referred patients from the emergency department (ED) and from GPs [where patient assessment occurs in the assessment and planning unit (APU)]; (2) preoperative length of stay (LOS[PO]); (3) length of stay of nonadmitted patients (LOS[NA]); (4) case volume "in h" (0730-1730) versus "after h"; and (5) readmission rate. Statistical analysis was performed with one-way ANOVA, regression, and chi(2) tests. RESULTS: Results show a reduction of mean time from referral to assessment from 2.28 to 1.6 h in the ED (p <= 0.001). Patients are seen in APU after GP referral sooner as well as the time from referral to assessment reducing from 2 to 1.76 h (p < 0.001). The LOS[PO] has not changed significantly overall (34.58 vs. 34.88 h, p = not significant [NS]). However, there are encouraging signs in high-volume procedures, such as appendicectomy. The mean LOS[PO] for appendicectomy was 7.81 h but is now 6.53 h (p <= 0.005). The LOS[NA] has decreased from 15.23 to 9.48 h (p < 0.005). Since the development of the ASU, the number of cases operated on "in hours" is increasing with a corresponding decrease in "after hours" operating. CONCLUSIONS: Our KPIs demonstrate an early positive trend of facilitating acute patient flow. There is minimal difference between pre- and post-ASU LOS[PO].The causes are likely multifactorial, including increased case volume displacing minor cases of lesser urgency, lack of operating staff, and shortage of hospital beds in winter months. This study supports the utility of ASU in facilitating patient flow in a NZ metropolitan public hospital. PMID- 22674094 TI - The positive non-sentinel status is not the main decisional factor for chemotherapy assignment in breast cancer with micrometastatic disease in the sentinel lymph node. AB - BACKGROUND: Surgical and systemic treatment modalities for breast cancer (BC) patients with micrometastatic disease in the sentinel lymph node biopsy (SNB) are controversial. The aim of this study was to evaluate decisional factors associated with assignment of adjuvant chemotherapy (CT). PATIENTS AND METHODS: In a retrospective multicentric European study we evaluated cases of primary BC patients who underwent SNB. Logistic regression (LR) and recursive partitioning analyses (RPA) were performed to determine factors associated with CT. RESULTS: Of the 172 patients with micrometastatic disease, 39.5% received adjuvant CT. In the group treated with CT, patients tended to be younger (P = 0.001), with higher grade (P = 0.001) and HER2 positive tumors (P = 0.006) compared to patients without CT. In multivariate LR, age (P = 0.0027), high grading (P = 0.01) HER2 positivity (P = 0.03), and positive non-SN status (P = 0.03) were significantly associated with CT. RPA demonstrated that tumor grade, and not the non-SN status, was the first split in the partition tree followed by HER2 status, and non-SN status influencing the probability for CT administration. CONCLUSION: High tumor grade is the main decisional factor followed by HER2 positivity and then by the positive non-SN status for CT in micrometastatic disease in the SN. PMID- 22674095 TI - Percutaneous mitral valvuloplasty using echocardiographic intercommissural diameter as reference for balloon sizing: a randomized controlled trial. AB - BACKGROUND: Percutaneous balloon mitral valvuloplasty is the preferred therapeutic strategy in patients with mitral stenosis, but it has shortcomings in a subset of patients. HYPOTHESIS: A new method of balloon sizing through echocardiographic measurement of the intercommissural diameter would be safe and effective and lead to better outcomes. METHODS: Eighty-six mitral-stenosis patients were randomly assigned to undergo balloon mitral valvuloplasty either with height-based balloon reference sizing (HBRS group, n = 43) or with balloons sized by the echocardiographic measurement of intercommissural diameter (EBRS group, n = 43). Postprocedural mitral valve area (MVA) and severity of mitral regurgitation (MR) were assessed via echocardiography and ventriculography. Intention-to-treat approach was applied for the statistical analysis. RESULTS: Baseline characteristics were not different between the groups. The mean of the estimated balloon reference sizes was significantly higher in the HBRS patients than in the EBRS group (26.4 +/- 0.92 mm, 95% confidence interval [CI]: 26.2-26.6 vs 24.5 +/- 1.03 mm, 95% CI: 24.2-24.7, respectively; P = 0.006). Final MVAs were significantly larger in the EBRS group (1.5 +/- 0.2 cm(2), 95% CI: 1.46-1.59 vs 1.4 +/- 0.2 cm(2), 95% CI: 1.35-1.47, respectively; P = 0.01). The occurrence of new or aggravated MR was significantly lower in the EBRS group as assessed both by echocardiography (P = 0.04) and ventriculography (P = 0.05). Mitral regurgitation was aggravated in 13 (29.3%) patients in the HBRS group and in 5 (11.5%) patients in the EBRS group. CONCLUSIONS: Percutaneous balloon mitral valvuloplasty via the Inoue technique using balloons sized by the echocardiographic measurement of the maximal commissural diameter is an effective and safe method that might lead to an acceptable increase in the MVA and significant decrease in the rate and severity of iatrogenic MR. PMID- 22674096 TI - Organising pneumonia presenting as acute life threatening pulmonary haemorrhage. AB - Organising pneumonia, previously called bronchiolitis obliterans organising pneumonia is a clinicopathological entity of unknown aetiology, which has been reported with increasing frequency. Various modes of presentation have been described such as cough, fever, weight loss and alveolar opacities on chest radiograph. Haemoptysis as primary presenting symptom has only rarely been reported. The authors report a case in which massive life-threatening haemoptysis was the major presenting symptom. No aetiology was identified for the haemoptysis and the diagnosis was confirmed on postmortem histology. This case highlights the importance of considering organising pneumonia in the differential diagnosis of acute severe haemoptysis. PMID- 22674097 TI - Aspiration pneumonia caused by inadvertent insertion of gastric tube in an obtunded patient postoperatively. AB - A nasogastric feeding tube is commonly inserted to facilitate patient meeting nutritional needs after oral surgery. But sometimes incorrect position may cause a severe iatrogenic damage. The authors present a case of an aspiration pneumonia complication with the result of malposition of nasogastric tube while the patient was intubated postoperatively. He recovered 3 weeks later with antibody therapy. PMID- 22674098 TI - Neonatal sepsis: A, B, C--don't ever forget herpes. AB - A 5-day-old male presents to the emergency department septic and jaundiced, is resuscitated and started on broad spectrum intravenous antibiotics. However tragically in this case despite showing initial signs of stabilisation, he deteriorated with refractory metabolic acidosis and disseminated intravascular coagulation, and later passed away. At postmortem, disseminated herpes simplex virus-1 (HSV-1) was found. Paediatricians are well aware of the risk factors for bacterial neonatal sepsis and actively seek information from parents to identify those children at risk. When however should a viral aetiology be considered? Should all neonates receive empirical therapy until proven otherwise? The authors review the literature surrounding neonatal HSV infection and discuss the potential pitfalls of empirical treatment. PMID- 22674099 TI - Transient foreign accent syndrome. AB - Foreign accent syndrome (FAS) is a poorly understood and studied syndrome as it is indeed a rare entity. Since its first description in 1907 by French neurologist Pierre Marie involving a patient who presented with an Alsatian accent, there are approximately only 60 cases reported in the literature. The majority of such cases of FAS have been secondary to cerebrovascular accidents. Of the cases in the literature, none report such a transitory nature of FAS. In this particular case, a 55-year-old male presented with a foreign accent. This FAS was triggered by ischemia and was reversed after a seizure, the first reported in the literature. PMID- 22674100 TI - Preventing overcorrection of hyponatraemia with desmopressin. AB - A 61-year-old woman was admitted with history of vomiting, diarrhoea and severe hyponatraemia (Na(+) 109). The cause of the hyponatraemia was due to intravascular volume depletion resulting in a non-osmotic release of antidiuretic hormone (ADH) with the added effects of a thiazide diuretic. She was also on fluoxetine which may induce inappropriate secretion of ADH. Despite cautious fluid replacement, the patient's serum sodium increased by 12 mmol/l over the first 18 h (and by 10 mmol/l over 12 h). This trajectory, coupled with the rapid decrease in urine osmolality, suggested that this patient was at risk of significant brain injury due to rapid correction of serum sodium. The use of desmopressin slowed the rise in serum sodium allowing brain adaptive mechanisms time to protect against osmotic demyelination. PMID- 22674101 TI - Culture negative endocarditis: a diagnostic and therapeutic challenge! AB - Infective endocarditis remains a diagnostic and therapeutic challenge. The authors report an older male who presented with a lower extremities rash and signs of cardiac failure. Echocardiography showed vegetations attached to the bio prosthetic aortic valve, however, with negative blood cultures. Further investigation revealed positive Bartonella serologies. The patient was diagnosed with Bartonella endocarditis affecting the prosthetic valve and started on appropriate antibiotics. Valvular surgery was refused by patient secondary to age and medical co-morbidities. The patient presented 10 days later with intracerebral haemorrhage and progression of the endocarditis as demonstrated on echocardiogram. Valve replacement was contraindicated at this occasion due to the intracerebral bleed. The patient had poor prognosis and a decision to withdraw care was made by the family. The authors demonstrate a case of complicated infective endocarditis caused by Bartonella species leading to multisystem involvement. This case highlights the need for urgent valve replacement in the setting of Bartonella endocarditis. PMID- 22674102 TI - The importance of a travel history in the preoperative assessment of an elective surgical patient. AB - The authors present the case of a 43-year-old gentleman who was admitted for an elective surgical removal of an eroded gastric band. The patient reported no medical concerns and other than a mild anaemia of haemoglobin of 10.6, his preoperative assessment was non-significant. Postoperatively, the patient spiked temperatures on multiple occasions. When a travel history was subsequently taken, the patient revealed he had returned from Nigeria the night before his elective surgery. The patient tested positive for Plasmodium falciparum malaria for which he was successfully managed with oral quinine and doxycycline, and recuperated well both from malaria and the surgery. P falciparum malaria is a medical emergency and increases the morbidity and mortality of anaesthesia and surgery. Travel histories are not currently routinely taken as part of the preoperative assessment for elective surgical admissions; the authors argue that it should become a mandatory part. PMID- 22674103 TI - Successful treatment of bleeding gastro-intestinal angiodysplasia in hereditary haemorrhagic telangiectasia with thalidomide. AB - Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterised by epistaxis, cutaneous telangiectasia and visceral arterio-venous malformations (AVMs). It affects approximately one in 5000 people. Control of sustained and repeated haemorrhages from telangiectasias in the nose and gut in patients who may be transfusion dependent is clinically challenging. After repeated endoscopic coagulations, multiple lesions often recur at other sites of gastro-intestinal tract, where endoscopic therapy or surgical resection is not possible. Hormonal therapy has been employed for more than 50 years but has recently been shown to be ineffective. Thalidomide, with its antiangiogenic mechanism of action, seems to be promising drug as a treatment option where other modalities have been unsuccessful. In this article, the authors discuss a novel treatment of bleeding gastro-intestinal angiodysplasia. PMID- 22674104 TI - Urosepsis complicated by a spontaneous bladder perforation. AB - The authors present a case of a 72-year-old diabetic male s/p pelvic irradiation for prostate carcinoma who arrived in the emergency department with complaints of shaking chills. After admission for urosepsis, he developed severe abdominal pain and examination revealed a diffusely tender abdomen. The patient was diagnosed with spontaneous urinary bladder perforation and underwent surgery. After several weeks of intravenous antibiotics, he was discharged with multiple drains in place and bilateral nephrostomy tubes. PMID- 22674105 TI - Gastrointestinal bleeding caused by gastritis cystica polyposa. PMID- 22674106 TI - Three cases of primary small vessel vasculitis of the skeletal muscle-an own entity. AB - Whereas systemic vasculitis is the most common form of vasculitis, vasculitis restricted to a single organ system is rare. Primary vasculitis restricted to striated skeletal muscle has been described in few case reports for polyarteritis nodosa and leucocytoclastic vasculitis, but not for small vessel vasculitis, type microscopic polyangiitis. The authors describe three patients with primary small vessel vasculitis of the skeletal muscle without evidence of other major organ involvement. All three patients presented with myalgias and highly elevated acute phase reactants while muscle weakness and elevated creatine kinase levels were not consistently present. Diagnoses were established by muscle biopsy and extensive search for potential causes of secondary vasculitis. Complete remission could be accomplished by steroids alone in only one case, while additional immunosuppressants were needed in the other two cases. Primary small vessel vasculitis of the skeletal muscle should be considered in patients presenting with myalgia and signs of systemic inflammation in the absence of other organ manifestations. Once diagnosed, aggressive systemic immunosuppression is appropriate. PMID- 22674107 TI - Gallstone pancreatitis after laparoscopic cholecystectomy. AB - This case report describes the rare presentation of an unknown dumbbell shaped (or hourglass with diaphragmatic membrane) gallbladder presenting as gallstone pancreatitis 5 months after laparoscopic cholecystectomy for cholelithiasis and our management strategy. This case highlights the importance of ensuring adequate exposure at the time of operation to prevent such presentations. PMID- 22674108 TI - Management of adrenal incidentaloma: size still matters. AB - A 56-year-old man was found to have an adrenal incidentaloma on a CT scan of the abdomen. Clinically and biochemically, the mass was not functional. MRI scan revealed a heterogeneously enhancing, T2-hyperintense, right-sided adrenal mass (4.5*6.5 cm). Meta-iodo-benzylguanidine scan was normal, making a diagnosis of pheochromocytoma unlikely. As the mass was larger that 4 cm, it was excised and histopathological examination revealed a rare, composite tumour: benign adrenal adenoma with haemangiomatous and myelolipomatous components. This case highlights the difficulties encountered by a clinician faced with investigating a potentially malignant adrenal mass (based on size) and correlates radiological findings with a rare histopathological specimen. PMID- 22674109 TI - Ependymoblastoma in an adult: a diagnostic challenge on cytology. AB - Ependymoblastoma is a rare, highly malignant brain tumour considered by most to be a subtype of primitive neuroectodermal tumour manifesting in young children. The authors present an unusual case of ependymoblastoma occurring in an 18-year old female, one of the oldest patients reported with this tumour. The crush smears were highly cellular comprising singly scattered small, round immature cells with fine granular chromatin. The paraffin sections showed a tumour composed of uniform, small-sized, primitive cells forming well defined multi layered rosettes with prominent mitoses. The tumour cells exhibited diffuse Vimentin and focal glial fibrillary acidic protein reactivity. A few cells showed S-100 reactivity. The patient underwent radiotherapy following complete tumour debulking but, succumbed to the disease within 2 months of diagnosis. PMID- 22674110 TI - Plantar angiomyxolipoma in a child. AB - Angiomyxolipoma, a lipoma variant with myxoid areas and vascular proliferation was originally described in 1996 and till date has only 12 cases in published literature. Only two cases have been reported in children involving buccal mucosa and knee, respectively. The authors report a case of angiomyxolipoma, on the plantar surface of the left foot, in a 4-year-old male child who presented to our institution in Abha city (Kingdom of Saudi Arabia). The significant differential diagnosis of this neoplasm from other similar lipomatous tumours occurring in adult and paediatric population is discussed. The importance of recognising these tumours lies in their recognition as separate entity and the present case may add to the knowledge, clinical behaviour and prognosis of these less reported lipomatous neoplasms. PMID- 22674111 TI - Simultaneously developed polymyositis and autoimmune hepatitis. AB - The inflammatory myopaties such as polymyositis (PM) and dermatomyositis (DM) are autoimmune inflammatory muscle disorders characterised by the development of proximal and often symmetrical muscle weakness. Levels of serum muscle enzymes such as creatine kinase (CK), lactate dehydrogenase (LDH), asparate aminotransferase (AST) and alanine aminotransferase (ALT) are usually elevated. However, high levels of AST, ALT and LDH, without a determination of CK, are often misdiagnosed with hepatic diseases. Conversely, concomitant elevations of AST, ALT and LDH along with CK in patients with PM and DM may be considered to be due to myopathy itself even in a case of coexistence of liver injury. Oral administration of prednisolone was begun at a dose of 60 mg/day, resulting in a good outcome. PMID- 22674112 TI - Vertebral artery dissection in weightlifter with performance enhancing drug use. AB - This case report describes a transient ischaemic attack secondary to vertebral artery dissection (VAD) in a young male body builder. This occurred following weight training with weights across the back and shoulders. The patient was also known to take multiple performance enhancing agents including anabolic steroids, slimming agents, stimulants and human growth hormone. Cases of VAD have been described with cervical manipulation in the past and an association between the use of anabolic steroids and embolic strokes has been described. To the authors knowledge, this is the first case describing a link between VAD, weight training and anabolic steroids. PMID- 22674113 TI - Dramatic weight loss associated with commencing clozapine. AB - The authors report the case of a 44-year-old man with a long history of chronic enduring schizophrenia who experienced dramatic weight loss after commencing treatment with clozapine, an antipsychotic medication characteristically associated with the greatest degree of weight gain among medical treatments for schizophrenia. He was obese with a body mass index (BMI) of 41.5 kg/m(2), but after commencing clozapine therapy he experienced an improvement in psychotic symptoms and 40% loss of his body weight attained through an altered diet and exercise regime, which resulted in him attaining a normal BMI of 24.8 kg/m(2). PMID- 22674114 TI - Syphilis mimicking idiopathic intracranial hypertension. AB - Idiopathic intracranial hypertension (IIH) is a condition of yet unknown aetiology affecting predominantly obese females of childbearing age. IIH is a diagnosis of exclusion as raised cerebrospinal fluid pressure may occur secondary to numerous other medical conditions. An atypical phenotype or an atypical disease course should alert the physician to reevaluate a presumed IIH-diagnosis. The authors report a case of a 32-year-old non-obese male with intracranial hypertension, secondary to a syphilitic central nervous system infection, initially misdiagnosed as being idiopathic. Upon relevant antibiotic treatment, signs and symptoms of elevated intracranial pressure resolved completely. Syphilis is a rare, but very important, differential diagnosis that in this case was clinically indistinguishable from IIH. PMID- 22674115 TI - Reversible cushing dilated cardiomyopathy mimicking peripartum cardiomyopathy with successful subsequent pregnancy. AB - A 29-year-old lady G4P3A0 has been admitted in her last trimester with features of peripartum cardiomyopathy. She was treated accordingly with comprehensive antifailure therapy. She lost follow-up but reappeared 12 weeks later with further deterioration of her heart failure, severe depression and osteoporotic multiple lumbar fractures. She turned to be having Cushing syndrome secondary to adrenal adenoma. Post adrenalectomy all her symptoms subsided and her cardiac function fully recovered as shown by stress echocardiography. She reconceived with uneventful pregnancy and delivery. PMID- 22674116 TI - Thoraco-pulmonary and hepatic actinomycosis: an autopsy report. AB - Actinomycosis is now a rare disease and death unheard of. Diagnosis is made challenging by its varied presentations and ability to be a 'great pretender'. This report describes a rare autopsy case of thoraco-pulmonary and hepatic actinomycosis with the preceding clinical presentation. PMID- 22674117 TI - Buckwheat allergy: a potential problem in 21st century Britain. AB - Buckwheat is commonly consumed in many parts of the world and has recently become more available in the UK. Buckwheat allergy is well recognised in parts of mainland Europe and Asia, typically associated with consumption of specific regional foods. No adult cases of buckwheat allergy in the UK have been reported in the literature. The authors present two cases of buckwheat allergy that presented to our UK allergy service recently. A 57-year-old man presented with anaphylaxis after eating home-baked bread prepared using buckwheat flour bought in France. In the second case, a 63-year-old lady presented with bronchospasm and urticaria after consuming health-food muesli. Sensitisation was confirmed in both cases by positive skin prick testing and specific IgE to buckwheat. Given the growing popularity of foods that may contain buckwheat, including ethnic and health-food ranges, buckwheat allergy is likely to become increasingly common in the UK. PMID- 22674118 TI - Studying the non-thermal effects of terahertz radiation on E. coli/pKatG-GFP biosensor cells. AB - Studies of the impact of terahertz radiation on living objects present a significant interest since its use for security systems is currently considered promising. We studied the non-thermal impact of terahertz radiation on E. coli/pKatG-gfp biosensor cells. The Novosibirsk free electron laser (NovoFEL), which currently has the world's highest average and peak power, was used as the source of terahertz radiation. We demonstrated that exposure to terahertz radiation at the wavelengths of 130, 150, and 200 um and a power of 1.4 W/cm(2) induces changes in green fluorescent protein (GFP) fluorescence values and thus induces the expression of GFP in E. coli/pKatG-gfp biosensor cells. Possible mechanisms of the E. coli response to non-thermal exposure to terahertz radiation are discussed. PMID- 22674119 TI - Physical stability of albinterferon-alpha(2b) in aqueous solution: effects of conformational stability and colloidal stability on aggregation. AB - Controlling aggregation in protein therapeutics is a significant challenge. In this study, the aggregation behavior of albinterferon-alpha(2b) , a genetic fusion protein combining human serum albumin and alpha-interferon, was examined as a function of solution conditions. The stability was monitored during agitation and during storage at elevated temperature, where the extent of aggregation was determined using size-exclusion chromatography. The osmotic second virial coefficient and the free energy of unfolding were measured for each sample. This study demonstrates that both increasing conformational stability and maximizing colloidal stability help to maintain the physical stability of albinterferon-alpha(2b). PMID- 22674121 TI - alpha-MnO2 nanotubes: high surface area and enhanced lithium battery properties. AB - A simple one-step route for preparing alpha-MnO(2) nanotubes is reported. The alpha-MnO(2) nanotubes exhibit a high surface area of 226 m(2) g(-1) and reversible capacity of 512 mA h g(-1) at a high current density of 800 mA g(-1) after 300 cycles, as well as cycling stability when measured as an anode in lithium batteries. PMID- 22674120 TI - Anti-tumor necrosis factor alpha treatment of interferon-alpha-induced murine lupus nephritis reduces the renal macrophage response but does not alter glomerular immune complex formation. AB - OBJECTIVE: To analyze the mechanism for the therapeutic effects of tumor necrosis factor alpha (TNFalpha) inhibition in a murine model of systemic lupus erythematosus. METHODS: We used the (NZB * NZW)F(1) (NZB/NZW) mouse model of interferon-alpha-induced lupus nephritis and treated mice with TNF receptor type II (TNFRII) Ig after TNFalpha expression was detected in the kidneys. Autoantibodies were measured by enzyme-linked immunosorbent assay (ELISA), and autoantibody- forming cells were determined using an enzyme-linked immunospot assay. Activation of splenocytes was analyzed by flow cytometry. Kidneys were harvested and analyzed using flow cytometry, immunohistochemistry, ELISA, Western blotting, and real-time polymerase chain reaction. RESULTS: TNFRII Ig treatment stabilized nephritis and markedly prolonged survival. Autoantibody production and systemic immune activation were not inhibited, but the renal response to glomerular immune complex deposition was attenuated. This was associated with decreases in renal production of chemokines, renal endothelial cell activation, interstitial F4/80(high) macrophage accumulation, tubular damage, and oxidative stress. In contrast, perivascular lymphoid aggregates containing B cells, T cells, and dendritic cells accumulated unabated. CONCLUSION: Our data suggest that TNFalpha is a critical cytokine that amplifies the response of the nephron to immune complex deposition, but that it has less influence on the response of the systemic vasculature to inflammation. PMID- 22674122 TI - Novel DMSO-based electrolyte for high performance rechargeable Li-O2 batteries. AB - A dimethyl sulfoxide (DMSO) based electrolyte is first proposed for rechargeable lithium-O(2) (Li-O(2)) batteries. Superior battery performances, including high discharge capacity and low charge potential, are successfully obtained. PMID- 22674123 TI - Basic immunocytochemistry for light microscopy. AB - Immunocytochemistry, the identification of cell- or tissue-bound antigens in situ, by means of a specific antibody-antigen reaction, tagged microscopically by a visible label, has a remarkably wide range of applications. The basic techniques are straightforward and can be adapted to explore the localisation of virtually any molecule of interest to the researcher in samples of normal and/or malignant cells. Heterogeneity can be mapped and loss or gain of immunoreactivity with tumour progression can be visualised. In this chapter, methodologies are given for appropriate preparation of cells and tissues, including cells cultured on coverslips (which can be used for live cell imaging), cell smears, frozen (cryostat) and fixed, paraffin wax-embedded tissue sections. Heat- and enzyme based antigen retrieval methods are covered. Basic detection methods, which can be readily adapted, are given for direct (labelled primary antibody), simple indirect (labelled secondary antibody), avidin-biotin (biotinylated primary antibody), avidin-biotin complex (ABC), peroxidase-anti-peroxidase or alkaline phosphatase-anti-alkaline phosphatase (PAP or APAAP), and polymer-based methods. The use of enzyme labels including horseradish peroxidase and alkaline phosphatase, and fluorescent labels, are considered. PMID- 22674124 TI - Lectin histochemistry to detect altered glycosylation in cells and tissues. AB - Lectins are naturally occurring carbohydrate-binding molecules. A very wide range of purified lectins are commercially available which exhibit a diversity of carbohydrate-binding preferences. They can be used in the laboratory to detect carbohydrate structures on, or in, cells and tissues in much the same way that purified antibodies can be employed to detect cell- or tissue-bound antigens using immunocytochemistry. As lectins can distinguish subtle alterations in cellular glycosylation, they are helpful in exploring the glycosylation changes that attend both transformation to malignancy and tumour progression. In this chapter, methodologies are given for appropriate preparation of many types of cell and tissue preparations, including cells cultured on coverslips (which can be used for live-cell imaging), cell smears, and frozen (cryostat) and fixed, paraffin wax-embedded tissue sections. Heat- and enzyme-based carbohydrate retrieval methods are covered. Basic detection methods, which can be readily adapted to the researcher's needs, are given for direct (labelled lectin), simple indirect (labelled secondary antibody directed against the lectin), and avidin biotin (biotinylated lectin) and avidin-biotin complex. The use of both the enzyme label, horseradish peroxidase, and fluorescent labels is considered. PMID- 22674125 TI - Histopathological assessment of metastasis. AB - In spite of advances in the fields of immunohistochemistry and molecular biology, in clinical practice much of the assessment of metastases still relies on light microscopy using conventional histological stains. This is not so much a reflection of a reluctance by histopathologists to adopt new techniques, but more an indication that for most malignancies an enormous amount of useful prognostic data can be gained from relatively unsophisticated assessment of tissues, and that many of the strongest studies of prognostic factors in malignancy predate the era of molecular diagnostics. Although it is undoubtedly true that newer techniques have added prognostic information in the assessment of many tumors, and many, such as the measurement of estrogen receptor status in breast cancer, could be considered routine, a skilled assessment of the morphology of the tissues still provides the fundamental basis of assessing prognosis in the vast majority of cases. PMID- 22674126 TI - Immunocytochemical detection and characterisation of individual micrometastatic tumour cells. AB - Detection of micrometastases in the bone marrow (BM) of cancer patients may be a helpful method for early detection of relapse. The diverse methodology employed across different laboratories, however, renders comparison of results difficult. This chapter describes a robust reliable system for the immunochemical detection of individual micrometastatic tumour cells from the BM aspirates of patients with solid epithelial tumours, based on the binding of antibody to cytokeratin proteins. PMID- 22674127 TI - The polymerase chain reaction. AB - The polymerase chain reaction (PCR) has had a significant impact on all aspects of the molecular biosciences, from cancer research to forensic science. The sensitivity and specificity inherent in the technique allow minute quantities of genetic material to be detected while the unique properties of thermostable DNA polymerase ensure that abundant copies are reliably reproduced to levels that can be visualized and/or used for further applications. This chapter describes applications of PCR and PCR-RT to investigate primary cancer and metastatic disease at both the DNA and mRNA expression levels. PMID- 22674128 TI - Sodium dodecyl sulphate-polyacrylamide denaturing gel electrophoresis and Western blotting techniques. AB - The study of proteins, their expression and post-translational modification, is a key process in molecular biology. Immunoblotting is a well-established and powerful tool for the study of proteins, which continues to evolve as new reagents and apparatus are developed. This chapter describes in detail the process by which proteins are extracted from cells, quantified, fractionated using poly-acrylamide gel electrophoresis, transferred to a membrane, and assessed by immunoblotting. Variations in experimental technique, and new technologies available to the researcher, are also discussed. PMID- 22674129 TI - 2-DE-based proteomics for the analysis of metastasis-associated proteins. AB - Two-dimensional electrophoresis (2-DE) is a high-resolution technique for analysis and comparison of complex protein mixtures. With the advent of recent technical developments, its application has become significant in a wide range of fields. This chapter describes a proteomic approach for the analysis of metastasis-associated proteins using pre-fractionation of glycosylated proteins via lectin (HPA) affinity chromatography prior to separation by 2-DE. Guidelines for the preparation and storage of buffers, experimental conditions and protocols of affinity chromatography, isoelectric focussing, and SDS-PAGE conditions are provided. Critical parameters associated with the different steps of 2-DE are discussed. PMID- 22674130 TI - Assessment of gelatinases (MMP-2 and MMP-9) by gelatin zymography. AB - Gelatin zymography is a simple yet powerful method to detect proteolytic enzymes capable of degrading gelatin from various biological sources. It is particularly useful for the assessment of two key members of the matrix metalloproteinase family, MMP-2 (gelatinase A) and MMP-9 (gelatinase B), due to their potent gelatin-degrading activity. This polyacrylamide gel electrophoresis-based method can provide a reliable assessment of the type of gelatinase, relative amount, and activation status (latent, compared with active enzyme forms) in cultured cells, tissues, and biological fluids. The method can be used to investigate factors that regulate gelatinase expression and modulate zymogen activation in experimental systems. The system provides information on the pattern of gelatinase expression and activation in human cancer tissues and how this relates to cancer progression. Interpretation of the data obtained in gelatin zymography requires a thorough understanding of the principles and pitfalls of the technique; this is particularly important when evaluating enzyme levels and the presence of active gelatinase species. If properly used, gelatin zymography is an excellent tool for the study of gelatinases in biological systems. PMID- 22674131 TI - Determination of cell-specific receptor binding using a combination of immunohistochemistry and in vitro autoradiography: relevance to therapeutic receptor targeting in cancer. AB - Mapping of receptor binding to specific structures, or cells within tissue samples, provides valuable information regarding biological and pathological mechanisms. Such information may potentially be translated into targeted therapies, especially in the field of cancer treatment. In this chapter, a receptor localization technique is described which utilises frozen sections of human tissue and combines immunohistochemistry (IHC) and micro-autoradiography. IHC utilises antibodies tagged to an enzymatic complex to identify specific cell types (such as epithelial cells or fibroblasts) within the tissue under investigation; this step is immediately followed by the second technique which is based on the use of radiolabelled compounds (radioligands) that selectively bind to preselected membrane receptors. This approach allows visualisation of cells of interest by immunohistochemical staining of tissue sections (colour product) in combination with the use of radiolabelled compounds that are detected following exposure to radiation-sensitive film or emulsion to produce a map of receptor distribution or localisation of cell-specific receptor binding. The system described has been used to compare receptor binding to cells in normal human colorectal tissue with that in colorectal cancer specimens. PMID- 22674132 TI - Fluorescence in situ hybridization for cancer-related studies. AB - Cytogenetic analysis of tumour material has been greatly enhanced over the past 30 years by the application of a range of techniques based around fluorescence in situ hybridization (FISH). Fluorescence detection for in situ hybridization has the advantage of including the use of a multitude of fluorochromes to allow simultaneous specific detection of multiple probes by virtue of their differential labelling and emission spectra. FISH can be used to detect structural (translocation/inversion) and numerical (deletion/gain) genetic aberrations. This chapter will deal with FISH methods to detect and localize one or more complementary nucleic acid sequences (probes) within a range of different cellular targets including metaphase chromosomes, nuclei from cell suspension, and formalin-fixed paraffin-embedded FFPE tissue sections. Methods for the efficient localization of probes to FFPE tissue cores in tissue microarrays (TMAs) are also described. PMID- 22674133 TI - Using a quartz crystal microbalance biosensor for the study of metastasis markers on intact cells. AB - The use of biosensors has become a standard method to characterize biomolecular interactions. Data obtained from biosensor studies are widely used to evaluate drug candidates, particularly in relation to their binding properties towards a selected target. The importance of measuring such interactions in a biologically relevant environment has become the new challenge for the biosensor technologies. In this chapter we describe a method for studying interactions between proteins and targets at the surface of intact cells using a quartz crystal microbalance (QCM) biosensor. PMID- 22674134 TI - Cell separations by flow cytometry. AB - Flow cytometry has become a standard method for separating individual subsets of cells from a heterogeneous population. Multilaser, multicolour cell sorters are increasingly common and have become more complex in recent years increasing the number of applications available. However, a cell sorting experiment is only as good as the input sample, and the preparation of this is extremely important. This chapter describes the methods used to prepare samples for flow cytometry and how they can be adapted and optimised according to cell type. PMID- 22674135 TI - Detection of putative cancer stem cells of the side population phenotype in human tumor cell cultures. AB - Human solid tumors and clonal tumor cell lines comprise phenotypically and functionally diverse subsets of cancer cells and also contain stem cell-like cancer cells. Side population (SP) cells, which pump out the fluorescent dye Hoechst 33342 (H33342) via the ABCG2 transporter, define a fraction of adult tissue stem cells in a wide variety of organs. Rare cancer cells with similar H33342 efflux capacity and delimited expression of ABCG2 are present in various types of human tumors, such as breast cancer, lung cancer, and hepatocellular carcinoma. These cancer SP cells display several properties attributable to stem cell-like cancer cells and have been implicated in tumor growth, progression, and metastasis. Here we provide a detailed protocol for the detection of putative cancer stem cells of the SP phenotype in human adherent breast cancer cell cultures. PMID- 22674136 TI - Genes involved in the metastatic cascade of medullary thyroid tumours. AB - The process of how a benign tumour turns invasive and capable to survive in distant organs remains poorly understood, despite the evidence that metastasis formation is the primary cause of cancer patient mortality. This ignorance is partly due to the lack of appropriate animal models from which to investigate this complex process. The retinoblastoma (Rb) tumour suppressor pathway (pRb/E2F) is mutated in almost all human tumours, and a number of laboratories have now established pRb- or E2F-deficient mouse models. Consistent with the role of mutation in retinoblastoma in cancer biology, Rb heterozygous mice are prone to develop tumours. Among the ensuing tumours, the medullary thyroid carcinomas (MTCs) have a lessened tendency to form secondary cancers and metastases. Intriguingly, if an E2f3 mutation is introduced in this genetic background, more aggressive MTCs develop, which metastasize more frequently. Gene chip microarrays, however, provide an unbiased approach for examining the genome-wide expression levels and enable identification of a large set of metastasis-enriched gene sets. The identified genes may simply represent putative markers of the disease stage. Alternatively, genes may be identified that causally determine a link to the onset of metastasis. We describe the use of gene chip microarrays for identification of putative markers enriched in metastatic mouse MTCs. The chapter details how the most promising candidates are verified using additional methods, such as quantitative real-time PCR. In this case, co-transfection of the E2F transcription factor using a heterologous reporter gene system is suggestive of E2Fs directly regulating putative metastasis markers. PMID- 22674137 TI - High-resolution quantitative methylation analysis of microRNA genes using PyrosequencingTM. AB - MicroRNA (miRNA) genes have been shown to perform a crucial role in breast cancer metastasis. The epigenetic inactivation of such microRNA genes, as a result of aberrant DNA methylation, is frequently found in human tumours including those of the breast, and this is an area of considerable research activity.PyrosequencingTM is a new quantitative method for the assessment of DNA methylation, with single CpG site resolution. PyrosequencingTM can easily be performed in a 96-well-plate format with a cost-effective medium-sized throughput.This chapter provides a general outline of DNA methylation analysis, a detailed protocol of the PyrosequencingTM procedure, and guidelines for the design of new assays. The strengths and limitations of this approach are discussed throughout the chapter. PMID- 22674138 TI - RNAi technology to block the expression of molecules relevant to metastasis: the cell adhesion molecule CEACAM1 as an instructive example. AB - Specific gene silencing using small hairpin RNA (shRNA) constructs offer researchers the possibility to study the influence of a single protein in the metastatic process. The role of the cellular adhesion molecule CEACAM1 on tumour formation and metastasis is of some interest. The human melanoma cell line FemX-1 was transfected with an shRNA construct directed against the CEACAM family. Stable clones were obtained and characterized via puromycin selection, single cell dilution, and subsequent FACS analysis. The cell line showed a knock-down of CEACAM1 of more than 85%. This knock-down remained stable when examined in an SCID mouse xenograft experiment over 40 days. PMID- 22674139 TI - Galectin-3 binding and metastasis. AB - Galectin-3 is a member of a family of carbohydrate-binding proteins. It is present in the nucleus, the -cytoplasm, and also the extracellular matrix (ECM) of many normal and neoplastic cell types. Reports show an upregulation of this protein in transformed and metastatic cell lines (Raz and Lotan Cancer Metastasis Rev 6: 433-452, 1987; Raz et al. Int J Cancer 46: 871-877, 1990). Moreover, in many human carcinomas, an increased expression of galectin-3 correlates with progressive tumor stages (Lotan et al. Int J Cancer 56: 474-480, 1994; Bresalier et al. Gastroenterology 115: 287-296, 1998; Nangia-Makker et al. Int J Oncol 7: 1079-1087, 1995; Xu et al. Am J Pathol 147: 815-822, 1995).Several lines of analysis have demonstrated that the galectins participate in cell-cell and cell matrix interactions by recognizing and binding complementary glycoconjugates and thereby play a crucial role in normal and pathological processes. Elevated expression of the protein is associated with an increased capacity for anchorage independent growth, homotypic aggregation, and tumor cell lung colonization (Lotan et al. Cancer Res 45: 4349-4353, 1985; Lotan and Raz J Cell Biochem 37: 107-117, 1988; Meromsky et al. Cancer Res 46: 5270-5275, 1986). In this chapter we describe the methods of purification of galectin-3 from transformed Escherichia coli and some of the commonly used functional assays for analyzing galectin-3 binding. PMID- 22674140 TI - Lectin array-based strategies for identifying metastasis-associated changes in glycosylation. AB - Since 2005, lectin microarray technology has emerged as a relatively simple yet powerful technique for the comprehensive analysis of glycoprotein glycosylation. Lectin microarrays represent a new analytical method that can be used to explore the human glycome, a unique source of markers of diseases including cancer. The lectin microarray technology is a sensitive tool with the potential to allow high throughput analysis of cancer-associated changes in glycosylation. This chapter describes the generation of a lectin-binding signature associated with metastatic primary breast tumours that have been resected, fixed, and embedded in paraffin. Procedures concerning sample and lectin microarray preparation are explained, alongside experimental considerations and approaches to data analysis. PMID- 22674141 TI - Efficacy and safety of eltrombopag in Japanese patients with chronic liver disease and thrombocytopenia: a randomized, open-label, phase II study. AB - BACKGROUND: Eltrombopag is an oral thrombopoietin receptor agonist that stimulates thrombopoiesis and shows higher exposure in East Asian patients than in non-Asian patients. We evaluated the pharmacokinetics, efficacy, and safety of eltrombopag in Japanese patients with thrombocytopenia associated with chronic liver disease (CLD). METHODS: Thirty-eight patients with CLD and thrombocytopenia (platelets <50,000/MUL) were enrolled in this phase II, open-label, dose-ranging study that consisted of 2 parts. In the first part, 12 patients received 12.5 mg of eltrombopag once daily for 2 weeks. After the evaluation of safety, 26 patients were randomly assigned to receive either 25 or 37.5 mg of eltrombopag once daily for 2 weeks in the second part. RESULTS: Pharmacokinetics showed that the geometric means of the maximum plasma concentration (C(max)) and the area under the curve (AUC) in the 12.5 mg group were 3,413 ng/mL and 65,236 ng h/mL, respectively. At week 2, the mean increases from baseline in platelet counts were 24,800, 54,000, and 60,000/MUL in the 12.5, 25, and 37.5 mg groups, respectively. The median platelet counts increased within 2 weeks of the beginning of administration in all groups, and remained at the same level throughout the 2 week post-treatment period in the 12.5 mg group, whereas the platelet counts peaked a week after the last treatment in both the 25 and 37.5 mg groups. Most adverse events reported were grade 1 or 2; 2 patients in the 37.5 mg group had drug-related serious adverse events. CONCLUSIONS: Eltrombopag ameliorated thrombocytopenia in Japanese patients with CLD and thrombocytopenia. The recommended dose for these patients is 25 mg daily for 2 weeks. PMID- 22674142 TI - Methylation alterations of WT1 and homeobox genes in inflamed muscle biopsy samples from patients with untreated juvenile dermatomyositis suggest self renewal capacity. AB - OBJECTIVE: To determine the effect of methylation alteration in inflamed muscles from children with juvenile dermatomyositis (DM) and other idiopathic inflammatory myopathies (IIMs). METHODS: Magnetic resonance imaging-directed diagnostic muscle biopsies yielded samples from 20 children with juvenile DM, which were used for genome-wide DNA methylation profiling, as were muscle biopsy samples from 4 healthy controls. Bisulfite treatment followed by pyrosequencing confirmed methylation status in juvenile DM and other IIMs. Immunohistochemistry defined localization and expression levels of WT1. RESULTS: Comparison of genome wide DNA methylation profiling between juvenile DM muscle and normal control muscle revealed 27 genes with a significant methylation difference between the groups. These genes were enriched with transcription factors and/or cell cycle regulators and were unrelated to duration of untreated disease. Six homeobox genes were among them; ALX4, HOXC11, HOXD3, and HOXD4 were hypomethylated, while EMX2 and HOXB1 were hypermethylated. WT1 was significantly hypomethylated in juvenile DM (Deltabeta = -0.41, P < 0.001). Bisulfite pyrosequencing verification in samples from 56 patients with juvenile DM confirmed the methylation alterations of these genes. Similar methylation alterations were observed in juvenile polymyositis (n = 5) and other IIMs (n = 9). Concordant with the other findings, WT1 protein was increased in juvenile DM muscle, with average positive staining of 11.6%, but was undetectable in normal muscle (P < 0.001). CONCLUSION: These results suggest that affected muscles of children with juvenile DM and IIMs have the capacity to be repaired, and that homeobox and WT1 genes are epigenetically marked to facilitate this repair process, potentially suggesting new avenues of therapeutic intervention. PMID- 22674143 TI - Enantioselective, transition metal catalyzed cycloisomerizations. AB - This review illustrates enantioselective transition-metal promoted skeletal rearrangements of polyunsaturated substrates possessing olefin, alkyne or allene functions. These processes are classified according to the number of carbon atoms involved in the cyclization, from (1C+1C) to (2C+2C+2C) or (2C+5C) cyclizations. Thus, for instance, (1C+1C) processes are typified notably by Alder-ene type reactions taking place mainly under palladium and rhodium catalysis, in the presence of chiral phosphorus ligands. Also, rhodium, platinum, and gold promoted insertions of unsaturated carbon-carbon bonds into C-H bonds belong to this class. For each class of reactions or substrate type the best ligand-metal pairs are highlighted. Unfortunately, unlike other transition metal promoted reactions, the mechanisms of chiral induction and stereochemical pathways have not been established so far in any of these reactions. In only a few instances, qualitative heuristic models have been tentatively proposed. Although the available stereochemical information is systematically given here, the paper focuses mainly on synthetic aspects of enantioselective cycloisomerizations. PMID- 22674145 TI - Cost effectiveness of gene expression profiling for early stage breast cancer: a decision-analytic model. PMID- 22674146 TI - Chemotherapy (CT) and hormonotherapy (HT) as neoadjuvant treatment in luminal breast cancer patients: results from the GEICAM/2006-03, a multicenter, randomized, phase-II study. AB - BACKGROUND: Luminal breast cancer is a highly endocrine responsive disease. However, the therapeutic benefit of chemotherapy (CT) in this population is not fully characterized. This study investigates the value of CT and hormone therapy (HT) in luminal breast cancer patients in the neoadjuvant setting. PATIENTS AND METHODS: Patients with operable breast cancer and immunophenotypically defined luminal disease (ER+/PR+/HER2-/cytokeratin 8/18+) were recruited. Patients were randomized to CT (epirubicin 90 mg/m(2) plus cyclophosphamide 600 mg/m(2) 4 cycles followed by docetaxel 100 mg/m(2 )4 cycles [EC-T]) or HT (exemestane 25 mg daily 24 weeks [combined with goserelin in premenopausal patients]). The primary end point was the clinical response measured by magnetic resonance imaging. RESULTS: Ninety-five patients were randomized (47 CT, 48 HT). The clinical response rate was 66% for CT and 48% for HT (P = 0.075). We performed an unplanned analysis based on Ki67 levels (cut-off of 10%). Similar clinical response was seen between arms in patients with low Ki67 (CT: 63%, HT: 58%; P = 0.74); patients with high Ki67 had a better response with CT (67 versus 42%; P = 0.075). Grade 3/4 toxicity was more frequent with CT. CONCLUSIONS: Luminal immunophenotype is not enough to identify patients who do not benefit from neoadjuvant CT. Luminal patients with low proliferation index could potentially avoid CT. PMID- 22674147 TI - Post-cancer fatigue is not associated with immune activation or altered cytokine production. AB - BACKGROUND: Prolonged fatigue after cancer treatment is common. The pathophysiology of such post-cancer fatigue (PCF) is unknown, although cross sectional studies suggest increased pro-inflammatory cytokine production. This study investigated the association between cytokine levels and fatigue from the time of treatment to 12 months later. PATIENTS AND METHODS: A representative nested case-control series was derived from a prospective cohort of women treated for early-stage breast cancer, including 13 PCF cases and 15 matched control subjects who recovered uneventfully. Serum levels and in vitro production of the cytokines interleukin (IL)-1alpha, IL-2, interferon (IFN)-gamma, IL-4, IL-6, IL 10, IL-12, and tumour necrosis factor (TNF)-beta were measured by multiplex immunoassay in longitudinally collected samples. In addition, serum levels of neopterin and the anti-inflammatory regulators, IL-1 receptor antagonist, sIL-6R, and sTNF-rII, were assayed by enzyme-linked immunosorbent assay. Flow cytometric analysis of activated leukocyte subsets was performed. RESULTS: No significant differences in any of these parameters were found between cases and control subjects. Cytokine levels and symptoms showed no clear correlation pattern. CONCLUSION: The findings in this well-characterised subject group argue against the notion that PCF is mediated by peripheral inflammation. PMID- 22674144 TI - The immunopathogenesis of celiac disease reveals possible therapies beyond the gluten-free diet. AB - Celiac disease is a T cell-mediated autoimmune inflammatory disease of the small intestine that is activated by gluten. The diagnosis of celiac disease is challenging as patients display a wide range of symptoms and some are asymptomatic. A lifelong gluten-free diet is the only currently approved treatment of celiac disease. Although the diet is safe and effective, the compliance rates and patient acceptance vary. Furthermore, many patients treated with a gluten-free diet continue to be mildly to severely symptomatic with persistent histological abnormalities, and a small number of patients develop refractory celiac disease. New therapeutic adjuncts and potential alternatives to the gluten-free diet could improve the treatment options for these patients. Advances in understanding the immunopathogenesis of celiac disease have suggested several types of therapeutic strategies that may augment or supplant the gluten free diet. Some of these strategies attempt to decrease the immunogenicity of gluten-containing grains by manipulating the grain itself or by using oral enzymes to break down immunogenic peptides that normally remain intact during digestion. Other strategies focus on preventing the absorption of these peptides, preventing tissue transglutaminase from rendering gluten peptides more immunogenic, or inhibiting their binding to celiac disease-specific antigen presenting molecules. Strategies that limit T cell migration to the small intestine or that reestablish mucosal homeostasis and tolerance to gluten antigens are also being explored. Additionally, it is vital to develop new therapeutic options for refractory celiac disease patients. This review highlights therapeutic strategies that may ultimately improve the health and well being of individuals with celiac disease. PMID- 22674148 TI - C-terminal deletions of Merkel cell polyomavirus large T-antigen, a highly specific surrogate marker for virally induced malignancy. AB - In 67-100% of cutaneous Merkel cell carcinomas (MCC) the Merkel cell polyomavirus (MCPyV) integrates into the host genome. Mutations and deletions truncating the C terminal helicase domain of the T-antigen (TAg) protein have been detected in these MCCs, but not in healthy skin specimens. C-terminal deletions of the TAg nucleic acid sequences are characteristic for about 38% of these cases. While the association of MCPyV with MCC has been proven, it is unknown whether MCPyV may play a similar role in other tumor entities. We describe in detail the development and validation of a novel Merkel cell polyomavirus TAg C-terminus deletion assay (MCPyV DeltaC-TAg). The triplex real-time PCR quantifies the N- and C-terminal part of the MCPyV TAg gene and the cellular beta-globin gene. By comparing the copy numbers of the N- and C-terminal part, deletions of the MCPyV TAg C-terminus are rapidly identified. MCPyV DeltaC-TAg was used to assess the physical state of MCPyV TAg in a large series of 55 MCCs, 15 cutaneous lymphomas and 47 forehead smears of healthy individuals. Neither DNA positivity nor viral load was able to discriminate MCCs from the other different types of samples. However, deleted TAg C-terminus sequences were detected only in MCPyV positive MCCs (39%). Consequently, detection of deleted C-terminal TAg sequences appears to be a highly specific surrogate marker for virally induced malignancy and should be used to support novel assumed MCPyV-tumor associations. The study further supports the notion that MCPyV does not play a role in cutaneous lymphoma pathogenesis. PMID- 22674150 TI - A point-by-point response to recent arguments against the use of statins in primary prevention: this statement is endorsed by the American Society for Preventive Cardiology. AB - Recently, a debate over the merits of statin therapy in primary prevention was published in the Wall Street Journal. The statin opponent claimed that statins should only be used in secondary prevention and never in any primary-prevention patients at risk for cardiovascular events. In this evidence-based rebuttal to those claims, we review the evidence supporting the efficacy of statin therapy in primary prevention. Cardiovascular risk is a continuum in which those at an elevated risk of events stand to benefit from early initiation of therapy. Statins should not be reserved until after a patient suffers the catastrophic consequences of atherosclerosis. Contrary to the assertions of the statin opponent, this principle has been demonstrated through reductions in heart attacks, strokes, and mortality in numerous randomized controlled primary prevention statin trials. Furthermore, data show that once a patient tolerates the initial treatment period, the few side effects that subsequently emerge are largely reversible. Accordingly, every major guidelines committee endorses statin use in secondary prevention and selectively in primary prevention for those with risk factors. The foundation for prevention remains increased physical activity, better dietary habits, and smoking cessation. However, prevention of heart attacks, strokes, and death from cardiovascular disease does not have to be all or none-all statin or all lifestyle. In selected at-risk individuals, the combination of pharmacotherapy and lifestyle changes is more effective than either alone. Future investigation in prevention should focus on improving our ability to identify these at-risk individuals. PMID- 22674151 TI - Skeletal dosimetry based on uCT images of trabecular bone: update and comparisons. AB - Two skeletal dosimetry methods using uCT images of human bone have recently been developed: the paired-image radiation transport (PIRT) model introduced by researchers at the University of Florida (UF) in the US and the systematic periodic cluster (SPC) method developed by researchers at the Federal University of Pernambuco in Brazil. Both methods use uCT images of trabecular bone (TB) to model spongiosa regions of human bones containing marrow cavities segmented into soft tissue volumes of active marrow (AM), trabecular inactive marrow and the bone endosteum (BE), which is a 50 um thick layer of marrow on all TB surfaces and on cortical bone surfaces next to TB as well as inside the medullary cavities. With respect to the radiation absorbed dose, the AM and the BE are sensitive soft tissues for the induction of leukaemia and bone cancer, respectively. The two methods differ mainly with respect to the number of bone sites and the size of the uCT images used in Monte Carlo calculations and they apply different methods to simulate exposure from radiation sources located outside the skeleton. The PIRT method calculates dosimetric quantities in isolated human bones while the SPC method uses human bones embedded in the body of a phantom which contains all relevant organs and soft tissues. Consequently, the SPC method calculates absorbed dose to the AM and to the BE from particles emitted by radionuclides concentrated in organs or from radiation sources located outside the human body in one calculation step. In order to allow for similar calculations of AM and BE absorbed doses using the PIRT method, the so-called dose response functions (DRFs) have been developed based on absorbed fractions (AFs) of energy for electrons isotropically emitted in skeletal tissues. The DRFs can be used to transform the photon fluence in homogeneous spongiosa regions into absorbed dose to AM and BE. This paper will compare AM and BE AFs of energy from electrons emitted in skeletal tissues calculated with the SPC and the PIRT method and AM and BE absorbed doses and AFs calculated with PIRT-based DRFs and with the SPC method. The results calculated with the two skeletal dosimetry methods agree well if one takes the differences between the two models properly into account. Additionally, the SPC method will be updated with larger uCT images of TB. PMID- 22674152 TI - Between-country comparison of whole-body SAR from personal exposure data in Urban areas. AB - In five countries (Belgium, Switzerland, Slovenia, Hungary, and the Netherlands), personal radio frequency electromagnetic field measurements were performed in different microenvironments such as homes, public transports, or outdoors using the same exposure meters. From the mean personal field exposure levels (excluding mobile phone exposure), whole-body absorption values in a 1-year-old child and adult male model were calculated using a statistical multipath exposure method and compared for the five countries. All mean absorptions (maximal total absorption of 3.4 uW/kg for the child and 1.8 uW/kg for the adult) were well below the International Commission on Non-Ionizing Radiation Protection (ICNIRP) basic restriction of 0.08 W/kg for the general public. Generally, incident field exposure levels were well correlated with whole-body absorptions (SAR(wb) ), although the type of microenvironment, frequency of the signals, and dimensions of the considered phantom modify the relationship between these exposure measures. Exposure to the television and Digital Audio Broadcasting band caused relatively higher SAR(wb) values (up to 65%) for the 1-year-old child than signals at higher frequencies due to the body size-dependent absorption rates. Frequency Modulation (FM) caused relatively higher absorptions (up to 80%) in the adult male. PMID- 22674153 TI - Particles shed from syringe filters and their effects on agitation-induced protein aggregation. AB - We tested the hypothesis that foreign particles shed from filters can accelerate the rate of protein aggregation and particle formation during agitation stress. Various types and brands of syringe filters were tested. Particle counts and size distribution (>=1 um) in buffer alone or in solutions of keratinocyte growth factor 2 (KGF-2) were determined with a micro-flow imaging. Submicron particle populations were characterized by dynamic light scattering. Loss of soluble protein during filtration or postfiltration incubation was determined by ultraviolet spectroscopy and bicinchoninic acid protein assay. There was a wide range (from essentially none to >100,000/mL) in the counts for at least 1 um particles shed into buffer or KGF-2 solution from the different syringe filters (with or without borosilicate glass microfibers). Filtration of KGF-2 with units containing glass microfibers above the membrane resulted in 20%-80% loss of protein due to adsorption to filter components. Filtration with systems containing a membrane alone resulted in 0%-20% loss of KGF-2. Effects of 24-h postfiltration incubation were tested on KGF-2 solution filtered with polyether sulfone membrane filters. Loss of soluble protein and formation of particles during agitation were much greater than that in control, unfiltered KGF-2 solutions. Similar acceleration of protein aggregation and particle formation was observed when unfiltered KGF-2 solution was mixed with filtered buffer and agitated. Particle shedding from syringe filters--and the resulting acceleration of protein aggregation during agitation--varied greatly among the different syringe filters and individual units of a given filter type. Our results demonstrate that nanoparticles and microparticles shed from the filters can accelerate protein aggregation and particle formation, especially during agitation. PMID- 22674154 TI - Impact of age and co-morbidities in patients with newly diagnosed glioblastoma: a pooled data analysis of three prospective mono-institutional phase II studies. AB - To analyse the impact of age and co-morbidities on compliance and outcomes in GBM patients enrolled in three prospective phase II trials. GBM patients (>= 18 years) were treated with radiotherapy (60 Gy) or enrolled in a Fractionated Stereotactic Conformal-Radiotherapy Phase II trial (69.4 Gy). Concomitant and adjuvant chemotherapy with Temozolomide (TMZ) was administered. Charlson Index Co morbidity (CCI) was used to assess co-morbidity. Toxicity was evaluated according to RTOG score. Survival analysis was performed by the Kaplan-Maier. Influence of age and co-morbidity was evaluated using log-rank test. From 2001 to 2008, 146 patients were enrolled: 56 (38.4 %) aged over 65 and 90 under 65. CCI >= 1 was observed in 41 % of elderly and 22 % of young group. Patients' compliance was 97.9 % for radio-chemotherapy. Acute toxicity was mild with no difference between the groups. Global median progression-free survival (PFS) and overall survival (OS) were 12 and 18 months, respectively. Age, surgery and radiation dose correlated with survival (p = 0.01, p = 0.04 and p = 0.03). CCI <= 2 did not show any influence on OS. Our data show that elderly with a good performance status and few co-morbidity may be treated as younger patients; moreover, age confirms a negative impact on survival while CCI <= 2 did not correlated with OS. PMID- 22674155 TI - Histamine contributes to increased RANKL to osteoprotegerin ratio through altered nuclear receptor 4A activity in human chondrocytes. AB - OBJECTIVE: To elucidate histamine receptor-mediated signaling pathways, transcriptional events, and target gene expression in human cartilage. METHODS: Histamine modulation of cartilage destruction was assessed by Safranin O staining and proteoglycan release. H(1) , H(2) , H(3) , and H(4) histamine receptor dependent regulation of transcription factors (nuclear receptor 4A1 [NR4A1], NR4A2, and NR4A3), RANKL, and osteoprotegerin (OPG) messenger RNA (mRNA) levels were measured in primary and SW-1353 chondrocyte cells using quantitative polymerase chain reaction and selective histamine receptor antagonists. Soluble RANKL and OPG protein levels were determined using enzyme-linked immunosorbent assays. NR4A protein levels and transactivity were evaluated by Western blot analysis, immunocytochemistry, and luciferase reporter assays. Stable depletion of NR4A1-3 was achieved by lentiviral transduction of NR4A short hairpin RNA. RESULTS: Primary human chondrocyte cells expressed differential steady-state levels of H(1) -H(4) histamine receptor mRNA. In combination with tumor necrosis factor alpha, histamine significantly promoted cartilage proteoglycan depletion and release. Histamine modulated the expression of NR4A1-3 orphan receptors in primary and immortalized human chondrocyte cells in a time- and concentration dependent manner. Histamine selectively signaled through H(1) and H(2) histamine receptors in chondrocytes to modulate RANKL and NR4A2 expression. The temporal effects of histamine on NR4A2 gene transcription were reduced in cells pretreated with inhibitors directed against protein kinase A, MAPK, and NF-kappaB signaling pathways. Histamine modulated the expression of RANKL with modest effects on OPG levels, leading to increased RANKL:OPG mRNA and protein ratios. Stable knockdown of NR4A1-3 expression resulted in reduced endogenous OPG levels and the loss of histamine-dependent regulation of RANKL expression. CONCLUSION: Our findings indicate that histamine, via H(1) and H(2) histamine receptors, contributes to joint disease by enhancing the ratio of RANKL to OPG expression through altered NR4A activity in human chondrocyte cells. PMID- 22674156 TI - Intravenous butorphanol administration reduces intrathecal morphine-induced pruritus after cesarean delivery: a randomized, double-blind, placebo-controlled study. AB - PURPOSE: Pruritus associated with intrathecal opioid administration is a common side effect. There is evidence that kappa-opioid receptor agonists have antipruritic activity. Butorphanol has agonist actions at both kappa-opioid and MU-opioid receptors. This study was designed to evaluate the antipruritic efficacy of butorphanol after intrathecal morphine administration in the setting of a randomized, double-blind study of parturients undergoing cesarean section. METHODS: Ninety-one women who received combined spinal-epidural anesthesia with 1.2 ml 0.5 % isobaric bupivacaine and 0.1 mg preservative-free morphine were included in this study. After delivery of the baby, the parturients were randomly allocated to two groups: butorphanol group (n = 46) and physiological saline group (n = 45). In the butorphanol group, parturients received an intravenous loading dose of 1 mg butorphanol followed by infusion of 0.2 mg/h butorphanol. The physiological saline group received an infusion of the same volume of physiological saline. The presence of pruritus, visual analog scores for pain, sedation scores, and adverse effects were recorded 1, 2, 4, 6, 8, 10, 12, and 24 h after intrathecal morphine administration. RESULTS: The incidence of pruritus at 24 h was significantly more frequent in the physiological saline group than in the butorphanol group (48.9 vs. 13.0 %, P < 0.001). The severity of pruritus was significantly greater in the saline group than in the butorphanol group 2, 4, 6, 8 and 10 h after intrathecal morphine injection (P = 0.004, 0.001, 0.002, and 0.003, respectively). The visual analog scale scores at 24 h were significantly lower in the butorphanol group than in physiological saline group (P < 0.001). The Ramsay sedation score in the butorphanol group was significantly higher than that in the physiological saline group after 1, 2, 4, 6, 8, 10, 12, and 24 h (P < 0.05). There were no significant differences between the two groups in nausea/vomiting and other adverse effects. CONCLUSION: Administration of intravenous butorphanol after delivery of the baby can reduce pruritus that has been induced by intrathecal morphine administration in cesarean delivery with combined spinal-epidural anesthesia. PMID- 22674157 TI - Comparison between lumbar and thoracic epidural morphine for severe isolated blunt chest wall trauma: a randomized open-label trial. AB - PURPOSE: The aim of this randomized, parallel-arm, open-label trial was to compare lumbar versus thoracic epidural morphine for severe isolated blunt chest wall injury as regards the incidence of pulmonary complications and pain control. METHODS: Fifty-five patients who sustained severe isolated blunt chest wall trauma were randomized using a computer-generated list to receive epidural morphine injection every 24 h through an epidural catheter inserted into the lumbar (n = 28) or thoracic (n = 27) region. Need for mechanical ventilation, incidence of pneumonia, arterial blood gas values, and pulmonary function tests were compared in both groups. Pain scores, supplemental analgesic consumption, length of intensive care unit (ICU) stay, and occurrence of epidural morphine related side effects were compared as well. Primary outcome measures were need for mechanical ventilation and incidence of pneumonia. RESULTS: Five (17.9 %) patients in the lumbar group were mechanically ventilated, compared with six (22.2 %) in the thoracic group (hazard ratio 1.35; 95 % CI 0.41-4.4; P = 0.611). Seven (25 %) patients in the lumbar group developed pneumonia versus six (22.2 %) in the thoracic group (hazard ratio 0.97; 95 % CI 0.33-2.9; P = 0.96). Both groups were comparable as regards the duration of mechanical ventilation (P = 0.141) and length of ICU stay (P = 0.227). Pain scores, supplemental analgesic consumption, pulmonary function, and occurrence of epidural morphine-related side effects were, likewise, comparable (P > 0.05). CONCLUSION: Lumbar and thoracic epidural morphine administered as once-daily injection to patients with severe isolated blunt chest wall trauma were comparable in terms of pain control, incidence of pulmonary complications, and occurrence of epidural morphine-related side effects. PMID- 22674158 TI - Receptor databases and computational websites for ligand binding. AB - Ligand binding to receptors is a key step in the regulation of cellular function by neurotransmitters, hormones, and many drugs. Not surprisingly then, genome projects have found that families of receptor genes form the largest groups of functional genes in mammalian genomes. A large body of experimental data have thus been generated on receptor-ligand interactions, and in turn, numerous computational tools for the in silico prediction of receptor-ligand interactions have been developed. Websites containing ligand binding data and tools to assess and manipulate such data are available in the public domain. Such Websites provide a resource for experimentalists studying receptor binding and for scientists interested in utilizing large data sets for other purposes, which include modeling structure-function relationships, defining patterns of interactions of drugs with different receptors, and computational comparisons among receptors. The Websites include databases of receptor protein and nucleotide sequences for particular classes of receptors (such as G-protein coupled receptors and nuclear receptors) and of experimental results from receptor-ligand binding assays, as well as computational tools for modeling the interactions between ligands and receptors and predicting the function of orphan receptors. In this chapter, we provide information and Uniform Resource Locators (URLs) for Websites that facilitate computational and experimental studies of receptor-ligand interactions. This list will be periodically updated at https://sites.google.com/site/receptorligandbinding/. PMID- 22674159 TI - How to use the IUPHAR receptor database to navigate pharmacological data. AB - Today's data-intensive, interdisciplinary research challenges scientists to keep up to date with key experimental techniques and tools reported in the literature. The International Union of Basic and Clinical Pharmacology Database (IUPHAR-DB) goes some way to addressing this need by providing expert-curated information sourced from primary literature and displayed in a user-friendly manner online. The database provides a channel for the IUPHAR Nomenclature Committee (NC-IUPHAR) to provide recommendations on the nomenclature of receptors and ion channels, to document their properties and the ligands that are useful for receptor characterization. Here we describe IUPHAR-DB's main features and provide examples of techniques for navigating and exploring the information. The database is freely available online at http://www.iuphar-db.org/. PMID- 22674160 TI - Radioligand binding assays and their analysis. AB - Radioligand binding is widely used to characterize receptors and determine their anatomical distribution, particularly the superfamily of seven transmembrane spanning G protein-coupled receptors for both established transmitters such as endothelin-1 and an increasing number of orphan receptors recently paired with their cognate ligands. Three types of assay are described. In saturation experiments, tissue sections, cultured cells, or homogenates are incubated with an increasing concentration of a radiolabeled ligand, which can be a labeled analog of a naturally occurring transmitter, hormone, or synthetic drug. Analysis using iterative nonlinear curve-fitting programs, such as KELL, measures the affinity of the labeled ligand for a receptor (equilibrium dissociation constant, K ( D )), receptor density (B (max)), and Hill slope (nH). The affinity and selectivity of an unlabeled ligand to compete for the binding of a fixed concentration of a radiolabeled ligand to a receptor are determined using a competition binding assay. Kinetic assays measure the rate of association to or dissociation from a receptor from which a kinetic K ( D ) may be derived. Quantitative autoradiography and image analysis is a sensitive technique to detect low levels of radiolabeled ligands and determine the anatomical distribution of receptors in sections that retain the morphology of the tissue. The measurement of bound radioligand within discrete regions of autoradiographical images using -computer-assisted image analysis is described. PMID- 22674161 TI - Use of scintillation proximity assay to measure radioligand binding to immobilized receptors without separation of bound from free ligand. AB - Scintillation proximity assay (SPA) is a bead-based homogeneous assay technology that removes the need for a filtration step to separate bound from free ligand in a receptor binding assay. SPA allows the rapid and sensitive assay of a wide range of molecular interactions in a homogeneous system and is routinely used for radioligand binding assays, particularly in drug screening applications where high throughput is required. Existing filter binding assays may be readily converted to SPA assays or assays may be directly developed in SPA format. This chapter describes the development of SPA radioligand binding assays detailing the choice of isotope, selection of SPA bead type, optimization of SPA bead and receptor ratio, optimization of assay buffer, selection of assay format, and assay validation including saturation binding, competition binding, and association/dissociation binding studies using SPA. PMID- 22674162 TI - Visualization and analysis of vascular receptors using confocal laser scanning microscopy and fluorescent ligands. AB - The use of fluorescent ligands to analyze receptor distribution is increasing in popularity. This is due to the ever growing number of fluorescent ligands and the increased sensitivity of microscope-based technologies. Image-analysis methods have advanced to a stage where quantification of fluorescent signals is relatively simple (if used appropriately). In this chapter we describe a method of analyzing the 2D and 3D distribution of fluorescent ligands in segments of blood vessels. In addition, we introduce the issues surrounding the accurate analysis of colocalization of two different fluorescent ligands. PMID- 22674163 TI - Dissecting the pharmacology of G protein-coupled receptor signaling complexes using bimolecular fluorescence complementation. AB - The affinity of G protein-coupled receptors (GPCRs) for particular ligands is altered by allosteric regulation with other proteins, for example signaling partners such as G proteins or beta-arrestins, or multimeric receptor complexes. Studying the ways in which such interactions modulate pharmacology requires techniques that report these events at the molecular level. Options include bimolecular fluorescence complementation (BiFC), an imaging-based method that can directly demonstrate protein-protein association in living cells. Commonly used fluorescent proteins are split into two nonfluorescent halves, which then tag the protein partners under investigation. Interaction between the partners brings the complementary fragments together, allowing refolding and regeneration of the fluorescent protein to indicate that association has occurred. BiFC is irreversible and is not a real-time technique, yet the simplicity of its fluorescent signal holds key advantages for quantification and cellular localization of the resultant complexes.This review introduces general experimental considerations for using the BiFC approach, and describes specific protocols to develop a BiFC assay for GPCR-beta-arrestin association, quantified using high content imaging and analysis. A further application of BiFC is to identify a particular protein-protein complex, thereby allowing investigation of its functional properties. This is illustrated in a protocol to quantify ligand induced internalization of GPCR dimers of precise composition. PMID- 22674164 TI - Live cell imaging of G protein-coupled receptors. AB - Live cell imaging experiments with G protein-coupled receptors (GPCRs) tagged with fluorescent fusion proteins were originally performed to study trafficking and subcellular location of these important drug targets. In the past decade, however, substantial progress came from improved imaging methods and from the cloning of novel fluorescent fusion proteins. Today, these methods allow to visualize not only GPCR interactions but also, e.g., receptor activation, trafficking between subcellular compartments, and to measure transport kinetics. Here, we summarize recent progress in live cell imaging of GPCRs using a confocal laser scanning microscope. PMID- 22674165 TI - Characterization of G-protein coupled receptor modulators using homogeneous cAMP assays. AB - More than two-thirds of all known G-protein coupled receptors are known to modulate the function of adenylate cyclase resulting in altered levels of cAMP. In turn, cAMP fluctuations transform agonist binding events into physiological changes in cell behavior. The advent of nonradioactive, homogeneous methods of measuring intracellular cAMP has enabled the rapid growth of drug discovery and research applications for these GPCR targets. In this chapter, we describe a nonradioactive, chemiluminescent cAMP detection method using enzyme fragment complementation technology to detect a wide range of GPCR modulators which is also suitable for high-throughput screening. PMID- 22674166 TI - Measurements of beta-arrestin recruitment to activated seven transmembrane receptors using enzyme complementation. AB - The recruitment of arrestins to activated 7TMRs results in the activation of alternative signaling pathways, quenching of G-protein activation, and coupling to clathrin-mediated endocytosis. The nearly ubiquitous involvement of arrestin in 7TMR signaling has spurred the development of several methods for monitoring this interaction in mammalian cells. Nonetheless, few maintain the reproducibility and precision necessary for drug discovery applications. Enzyme fragment complementation technology (EFC) is an emerging protein-protein interaction technology based on the forced complementation of a split enzyme that has proven to be highly effective in monitoring the formation of GPCR-arrestin complexes. In these systems, the target proteins are fused to two fragments of an enzyme that show little or no spontaneous complementation. Interaction of the two proteins forces the complementation of the enzyme, resulting in an enzymatic measure of the protein interaction. This chapter discusses the utility and methods involved in using the PathHunter beta-galactosidase complementation system to monitor arrestin recruitment and the advantages of exploiting this pathway in the characterization of 7TMR function. PMID- 22674167 TI - Quantitative phosphor imaging autoradiography of radioligands for positron emission tomography. AB - Imaging using phosphor screens have increasingly been employed for the analysis of radioactive samples in molecular biology, pharmacology, and receptor autoradiography. The major advantages of phosphor screens compared to radiation sensitive film are their greatly increased sensitivity, reducing exposure times with at least one order of magnitude, and their increased linear dynamic range. These features make phosphor screens ideal for imaging short-lived radionuclides, where exposure times are limited, such as (11)C and (18)F widely used to label radioligands for positron emission tomography (PET). Phosphor imaging can also considerably reduce exposure times for weak beta-particle emitters such as (3)H. In this chapter, we present methods for the characterization and evaluation of novel PET radioligands using quantitative phosphor imaging autoradiography. PMID- 22674168 TI - Dynamic in vivo imaging of receptors in small animals using positron emission tomography. AB - Positron emission tomography (PET) is a functional imaging technique with the potential to image and quantify receptors in vivo with high sensitivity. PET has been used extensively to study major neurotransmitters such as dopamine, serotonin, and benzodiazepine in humans as well as proving to be a very powerful tool to accelerate development and assessment of existing and novel drugs. With the recent development of dedicated PET scanners for small animals, such as the microPET, it is now possible to perform functional imaging in small animals such as rodents at high resolution. This will allow the study of animal models of disease and longitudinal studies in these models to monitor disease progression or effect of treatment in the same animal. Furthermore, the complete pharmacokinetics of a drug as well as pharmacodynamic information can be obtained in a single animal. Thus, small animal imaging will significantly reduce the number of animals needed for this type of experiment as well as reducing the effect of inter-animal variation. Experimental protocols in small animal imaging potentially can be very labor intensive. In this chapter, we discuss methods and practical aspects related to this type of experiment using the microPET system. PMID- 22674169 TI - Cellular localization of receptors using antibodies visualized by light and dual labeling confocal microscopy. AB - Immunocytochemistry can be used to visualize the binding of specific site directed antisera to receptors in tissue sections and permits the precise identification of cell types expressing a particular receptor when viewed using a conventional light microscope or by confocal microscopy. Protocols are also described for the dual labeling of cells in the same section using primary antisera raised in two different species (one to the receptor of interest, the second to an immunogen such as a cell-specific marker or the endogenous ligand) with the corresponding secondary antisera conjugated to different fluorescent dyes.The technique has a range of applications. Subtypes of receptors can be identified and distinguished prior to the development of selective agonists or antagonists, which is particularly important for mapping orphan receptors, where the identity of the endogenous ligand in not yet known. The deletion of genes encoding receptors, particularly in mice, has emerged as a powerful tool in understanding the role of a specific receptor in physiological processes. Receptor immunocytochemistry can be used to analyze the resulting phenotype in whole body sections of mice without preselection of the tissue to be studied. PMID- 22674170 TI - Detection of mRNA encoding receptors by in situ and Northern hybridization. AB - The ability to measure mRNA encoding protein is attractive, since, provided certain criteria are met, the investigator can be confident of highly selective detection. In addition, changes in mRNA expression as well as their precise cellular localization, provides the scientist with important information that may not be evident by the detection of the translated protein. Hence, the combined approach of assessing mRNA and protein expression will often allow a more precise hypothesis to be formulated. In the present chapter, we describe methods we have optimized for the detection of mRNA following extraction from tissue or cells (Northern hybridization) and the detection of specific mRNA transcripts within their synthesising cells (in situ hybridization). PMID- 22674171 TI - Delivery of molecules into cells using localized single cell electroporation on ITO micro-electrode based transparent chip. AB - Single cell electroporation is one of the nonviral method which successfully allows transfection of exogenous macromolecules into individual living cell. We present localized cell membrane electroporation at single-cell level by using indium tin oxide (ITO) based transparent micro-electrodes chip with inverted microscope. A focused ion beam (FIB) technique has been successfully deployed to fabricate transparent ITO micro-electrodes with submicron gaps, which can generate more intense electric field to produce very localized cell membrane electroporation. In our approach, we have successfully achieved 0.93 MUm or smaller electroporation region on the cell surface to inject PI (Propidium Iodide) dye into the cell with 60 % cell viability. This experiments successfully demonstrate the cell self-recover process from the injected PI dye intensity variation. Our localized cell membrane electroporation technique (LSCMEP) not only generates reversible electroporation process but also it provides a clear optical path for potentially monitoring/tracking of drugs to deliver in single cell level. PMID- 22674172 TI - Genetic diversity of bloom-forming Microcystis (cyanobacteria) populations in a hyper-eutrophic pond in central China. AB - Sequencing the environmental rRNA genes of Microcystis populations, such as by internal transcribed spacer (ITS), has been proven to provide a new insight into the genetic diversity of Microcystis in freshwater. In this study, a 19-month monitoring of Microcystis populations in a hyper-eutrophic pond in Wuhan city, China was conducted through molecular method by sequencing ITS fragments from the environmental DNA library. Three hundred twenty ITS genotypes of Microcystis in this pond were identified from a total of 563 sequences, thus exhibiting high genetic diversity of Microcystis in the pond. Dramatic changes and succession in ITS genotypes were also found during the survey period. Despite the absence of significant dominant ITS genotypes in the pond, several main genotypes were found to have been dominated for a short term. However, Microcystis ITS genotype patterns from 2007 to 2008 presented a complicated situation in this pond. The parsimony network (TCS) analysis showed that two groups were formed based on ITS genotypes. PMID- 22674173 TI - Multipurpose instantaneous microarray detection of acute encephalitis causing viruses and their expression profiles. AB - Detection of multiple viruses is important for global analysis of gene or protein content and expression, opening up new prospects in terms of molecular and physiological systems for pathogenic diagnosis. Early diagnosis is crucial for disease treatment and control as it reduces inappropriate use of antiviral therapy and focuses surveillance activity. This requires the ability to detect and accurately diagnose infection at or close to the source/outbreak with minimum delay and the need for specific, accessible point-of-care diagnosis able to distinguish causative viruses and their subtypes. None of the available viral diagnostic assays combine a point-of-care format with the complex capability to identify a large range of human and animal viruses. Microarray detection provides a useful, labor-saving tool for detection of multiple viruses with several advantages, such as convenience and prevention of cross-contamination of polymerase chain reaction (PCR) products, which is of foremost importance in such applications. Recently, real-time PCR assays with the ability to confirm the amplification product and quantitate the target concentration have been developed. Furthermore, nucleotide sequence analysis of amplification products has facilitated epidemiological studies of infectious disease outbreaks and monitoring of treatment outcomes for infections, in particular for viruses that mutate at high frequency. This review discusses applications of microarray technology as a potential new tool for detection and identification of acute encephalitis-causing viruses in human serum, plasma, and cell cultures. PMID- 22674174 TI - Construction of EGFP-labeling system for visualizing the infection process of Xanthomonas axonopodis pv. citri in planta. AB - Xanthomonas axonopodis pv. citri (Xac) is the causal agent of citrus bacterial canker, an economically important disease to world citrus industry. To monitor the infection process of Xac in different citrus plants, the enhanced green florescent protein (EGFP) visualizing system was constructed to visualize the propagation and localization in planta. First, the wild-type Xac was isolated from the diseased leaves of susceptible 'Bingtang' sweet orange, and then the isolated Xac was labeled with EGFP by triparental mating. After PCR identification, the growth kinetics and pathogenicity of the transformants were analyzed in comparison with the wild-type Xac. The EGFP-labeled bacteria were inoculated by spraying on the surface and infiltration in the mesophyll of 'Bingtang' sweet orange leaves. The bacterial cell multiplication and diffusion processes were observed directly under confocal laser scanning microscope at different intervals after inoculation. The results indicated that the EGFP labeled Xac releasing clear green fluorescence light under fluorescent microscope showed the infection process and had the same pathogenicity as the wild type to citrus. Consequently, the labeled Xac demonstrated the ability as an efficient tool to monitor the pathogen infection. PMID- 22674175 TI - Clinical value of ELISA-MPT64 for the diagnosis of tuberculous pleurisy. AB - Tuberculous pleurisy is one of the common extrapulmonary tuberculosis diseases. However, the diagnosis of tuberculous pleurisy still lacks a useful and effective tool, mainly due to paucity of Mycobacterium tuberculosis organisms in pleural effusion. Previous studies have confirmed that the MPT64 protein is highly specific and is secreted only by M. tuberculosis (MTB) complex. Therefore, in this study, we developed ELISA based on recombinantly expressed MPT64 in combination with rabbit polyclonal antibodies. The ELISA-MPT64 method was validated using MTB strains and tested against clinical samples. Nested PCR, Lowenstein-Jensen (L-J) culture and smear microscopy were employed as the comparative tools for assessing the performance of the assay. Our results demonstrate that the newly established ELISA-MPT64 technique is a rapid and useful tool for the diagnosis of tuberculous pleurisy. PMID- 22674176 TI - Do mouse models reflect the diversity of osteoarthritis in humans? PMID- 22674177 TI - The evaluation of a novel model of providing ward pharmacy services. AB - BACKGROUND: In UK hospitals, traditional ward pharmacy services involve pharmacists visiting their wards once or twice a day each weekday. However, to provide a more patient orientated ward pharmacy service, we developed the Imperial Model of Ward Pharmacy. This is based on pharmacists seeing every drug chart every other day, allowing increased focus towards patients' needs on other days. OBJECTIVE: To assess the impact of the Imperial Model of Ward Pharmacy on the prevalence of new medication orders that have not been screened by pharmacists, and doses omitted due to medication being unavailable. METHOD: We conducted an uncontrolled before-and-after study on eight medical wards. In each phase, we collected data on the number and prevalence of active medication orders that had not been screened by a pharmacist at the point of data collection, and the number and prevalence of regular doses documented as being omitted due to drug unavailability, or for which the administration record was left blank. RESULTS: The prevalence of unscreened medication orders reduced from 7.6 % of 1,433 orders to 4.1 % of 1,495 orders (p = 0.0002; Chi square test). There was no change in the prevalence of dose omissions (1.4 % in each phase of the study). CONCLUSION: This is a practical way to move to a more patient-focused service without affecting the safety of the service provided. PMID- 22674178 TI - Evaluating real-life clinical and economical burden of amphotericin-B deoxycholate adverse reactions. AB - BACKGROUND: Amphotericin-B (AMB) is associated with toxicity such as renal impairment, hypokalemia and infusion-related events (IRE). With the advent of AMB lipid formulations and newer antifungal drugs, presenting improved safety profiles, it was suggested that using the conventional deoxycholate (AMB-D) formulation should no longer be regarded acceptable. OBJECTIVES: Evaluation of real-life incidence of AMB-D-related adverse-drug effects (ADE) and associated costs. SETTING: Hadassah Hebrew University Medical Center, Jerusalem, Israel, a tertiary 1,100-bed teaching hospital. METHODS: A 1-year single-center prospective observational study following all patients administered AMB-D. Various parameters related to AMB-D administration were recorded. Main outcome measures Subsequent ADE-related events, discontinuations, switch to alternative antifungals and related resource-utilization were monitored. RESULTS: Among 119 patients (60 children, 59 adults) receiving AMB-D, serum creatinine doubling from baseline, hypokalemia and IRE occurred in 14.3 % (15 % in children, 13.6 % in adults), 16.8 % (16.6 % in children, 16.9 % in adults) and 10.9 % (10 % in children, 11.8 % in adults), respectively. AMB-D was discontinued due to an ADE in 12.6 % of patients (6.7 % in children, 18.6 % in adults). The total annual cost associated with AMB D use was 58,600. CONCLUSION: The clinical as well as economic burden of AMB-D associated ADE, as observed in real-life settings, appears to be manageable. Considering the significant cost implications associated, as suggested by simulated evaluation of an overall theoretic replacement of AMB-D by an equivalent volume of alternative antifungals, total abandonment of AMB-D appears unjustified. PMID- 22674180 TI - Characterization of supramolecular polymers. AB - Supramolecular polymers are made of monomers that are held together by noncovalent interactions. This is the reason for the wide range of novel properties, such as reversibility and responses to stimuli, exhibited by supramolecular polymers. A range of supramolecular polymerization methods have been developed leading to a number of novel supramolecular materials. However, standard techniques for the characterization of supramolecular polymers have yet to be established. The dynamic nature of supramolecular polymers makes them difficult to be fully characterized using conventional polymer techniques. This tutorial review summarizes various methods for characterizing supramolecular polymers, including theoretical estimation, size exclusion chromatography, viscometry, light scattering, vapor pressure osmometry, mass spectrometry, NMR spectroscopy, scanning probe microscopy, electron microscopy, and atomic force microscopy-based single molecule force spectroscopy. Each of these methods has its own particular advantages and disadvantages. Most of the methods are used to characterize the supramolecular polymer chain itself. However, some of the methods can be used to study the self-assembled state formed by supramolecular polymers. The characterization of a supramolecular polymer cannot be realized with a single method; a convincing conclusion relies on the combination of several different techniques. PMID- 22674179 TI - Exploring patients' motivation to participate in Australia's Home Medicines Review program. AB - BACKGROUND: Patients at risk of experiencing medicine-related problems do not always appear willing to participate in collaborative medication management services. Little is known about the psycho-social factors which motivate patients to participate in these services. The theory of motivated information management (TMIM) suggests that patients' willingness to participate may be motivated by their uncertainty and worry about their medicines. OBJECTIVE: The objective of this study was to investigate factors which may motivate patients to participate in a collaborative medication management program. SETTING: Fourteen semi structured focus group interviews held throughout Australia provided the data for the study. Eighty participants were recruited by community pharmacists. Participants were recruited into the study if they had experienced Australia's Home Medicines Review (HMR) program or would be eligible to participate in the program because they were at risk of experiencing medicine-related problems. Methods An interview guide was developed which was informed by TMIM. Focus group data were audio-recorded, transcribed and where necessary, translated into English. MAIN OUTCOME MEASURE: Qualitative data were thematically analysed to identify participants' expectations about the outcomes of HMR and the factors which may influence these expectations. RESULTS: Participants' most salient outcome expectancies of HMR were that it was a medication-information source which would assist them to manage their medicines. Recipients of the program held overall positive outcome expectancies, whereas nonrecipients' expectancies varied widely. Consistent with theory, participants who expressed some worry about their medicines, generally held positive outcome expectancies and were willing to participate in HMR. Compared with younger participants, older participants (those aged >74 years) tended to engage less in their thoughts about being at risk, and consequently did not experience worry. CONCLUSION: Worry about medicines is a key factor in motivating participants to engage in medicines information-seeking. Older persons who rely heavily on heuristics appeared less likely to worry about their medicines and willing to participate in medication management services. Age related reduction in the motivation to participate may have important implications for medication safety. Further examination of this effect is warranted because older persons are at greatest risk of medicine related problems. PMID- 22674181 TI - Influence of KRAS mutation status in metachronous and synchronous metastatic colorectal adenocarcinoma. AB - BACKGROUND: Mutations in the v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) are present in approximately 30% to 40% of colorectal adenocarcinomas. Wild-type (WT) KRAS mutation status is predictive of tumor response with epidermal growth factor receptor-directed therapies, but the results from studies evaluating the prognostic value of KRAS status in localized disease have been contradictory. The prognostic value of KRAS in metastatic disease, specifically according to whether patients have synchronous or metachronous disease at presentation, is less understood. METHODS: One-hundred ten consecutive patients with metastatic colorectal adenocarcinoma underwent testing for KRAS exon 2 mutations by polymerase chain reaction amplification and direct nucleotide sequencing. The clinical characteristics, treatments, and outcomes of these patients were then analyzed retrospectively, stratified according to whether patients presented with synchronous or metachronous metastasis and according to KRAS mutation status (WT or mutated). RESULTS: For the entire cohort, the median overall survival from the date of diagnosis of metastatic disease was 34.3 months (95% confidence interval, 28.3-49.4 months) for patients with WT KRAS (n = 70). The median overall survival for patients with mutated KRAS (n = 40) was 40.3 months (95% confidence interval, 27.9-51.1 months; log-rank P = .91). Kaplan Meier survival analysis indicated that 3-year overall survival and 5-year overall survival were not statistically different. Within the subgroups of patients with synchronous and metachronous metastatic disease, no significant differences were observed in median overall survival, 3-year overall survival, or 5-year overall survival between the WT KRAS and mutated KRAS groups. CONCLUSIONS: In this study, KRAS mutation status did not influence overall survival in either synchronous or metachronous metastatic colorectal adenocarcinoma and, as such, had no prognostic role in this disease setting. PMID- 22674182 TI - Identification of seven serum microRNAs from a genome-wide serum microRNA expression profile as potential noninvasive biomarkers for malignant astrocytomas. AB - The involvement of circulating microRNAs (miRNAs) in cancer and their potential as biomarkers of diagnosis and prognosis are becoming increasingly appreciated; however, little is known about circulating miRNA profiles in astrocytomas. In our study, we performed genome-wide serum miRNA analysis by the Solexa sequencing followed by validation conducted in the training and verification sets with a stem-loop quantitative reverse-transcription PCR (RT-qPCR) assay from serum samples of 122 untreated astrocytomas patients (WHO grades III-IV) and 123 normal controls. Identified miRNAs were subsequently examined in 55 grade II, 15 grade I astrocytomas, 11 astrogliosis, 42 other primary brain tumors and 8 tumor tissues from grades II-IV astrocytomas. In addition, paired serum samples before and after operation were collected from 14 malignant astrocytomas to determine the effect of surgery on the miRNAs' levels. A marked difference in serum miRNA profile was observed between high-grade astrocytomas and normal controls. Seven miRNAs were validated by RT-qPCR assay to be significantly decreased in grades II IV patients (p < 0.001), including miR-15b*, miR-23a, miR-133a, miR-150*, miR 197, miR-497 and miR-548b-5p, and the seven-miRNA panel demonstrated a high sensitivity (88.00%) and specificity (97.87%) for malignant astrocytomas prediction. These identified miRNAs also exhibited a global decrease in tumor tissues relative to normal tissues. Furthermore, these miRNAs in serum were markedly elevated after operation (p < 0.001). In addition, some of these serum miRNAs were significantly different between malignant and benign cases, astrogliosis and other primary brain tumors. The seven serum miRNAs identified in our study hold potential as noninvasive biomarker for malignant astrocytomas. PMID- 22674184 TI - Fractal network dimension and viscoelastic powerlaw behavior: I. A modeling approach based on a coarse-graining procedure combined with shear oscillatory rheometry. AB - Recent advances in dynamic elastography and biorheology have revealed that the complex shear modulus, G*, of various biological soft tissues obeys a frequency dependent powerlaw. This viscoelastic powerlaw behavior implies that mechanical properties are communicated in tissue across the continuum of scales from microscopic to macroscopic. For deriving constitutive constants from the dispersion of G* in a biological tissue, a hierarchical fractal model is introduced that accounts for multiscale networks. Effective-media powerlaw constants are derived by a constitutive law based on cross-linked viscoelastic clusters embedded in a rigid environment. The spatial variation of G* is considered at each level of hierarchy by an iterative coarse-graining procedure. The establishment of cross-links in this model network is associated with an increasing fractal dimension and an increasing viscoelastic powerlaw exponent. This fundamental relationship between shear modulus dynamics and fractal dimension of the mechanical network in tissue is experimentally reproduced in phantoms by applying shear oscillatory rheometry to layers of tangled paper strips embedded in agarose gel. Both model and experiments demonstrate the sensitivity of G* to the density of the mechanical network in tissue, corroborating disease-related alterations of the viscoelastic powerlaw exponent in human parenchyma demonstrated by in vivo elastography. PMID- 22674185 TI - Efficiency of a new strategy involving a new class of natural hetero-ligand iron(III) chelates (Fe(III)-NHL) to improve fruit tree growth in alkaline/calcareous soils. AB - BACKGROUND: Iron (Fe) chlorosis is a serious problem affecting the yield and quality of numerous crops and fruit trees cultivated in alkaline/calcareous soils. This paper describes the efficiency of a new class of natural hetero ligand Fe(III) chelates (Fe-NHL) to provide available Fe for chlorotic lemon trees grown in alkaline/calcareous soils. These chelates involve the participation in the reaction system of a partially humified lignin-based natural polymer and citric acid. RESULTS: First results showed that Fe-NHL was adsorbed on the soil matrix while maintaining available Fe for plants in alkaline/calcareous solution. The effects of using three different sources as Fe fertilisers were also compared: two Fe-NHL formulations (NHL1, containing 100% of Fe as Fe-NHL, and NHL2, containing 80% of Fe as Fe-NHL and 20% of Fe as Fe ethylenediamine-N,N'-bis-(o-hydroxyphenylacetic) acid (Fe-EDDHA)) and Fe-EDDHA. Both Fe-NHL formulations increased fruit yield without negative effects on fruit quality in comparison with Fe-EDDHA. In the absence of the Fe-starter fraction (NHL1), trees seemed to optimise Fe assimilation and translocation from Fe-NHL, directing it to those parts of the plant more involved in development. CONCLUSION: The field assays confirmed that Fe-NHL-based fertilisers are able to provide Fe to chlorotic trees, with results comparable to Fe-EDDHA. Besides, this would imply a more sustainable and less expensive remediation than synthetic chelates. PMID- 22674186 TI - Construction and application of a food-grade expression system for Lactococcus lactis. AB - A food-grade host/vector expression system for Lactococcus lactis was constructed using alanine racemase gene (alr) as the complementation marker. We obtained an alanine racemase auxotrophic mutant L. lactis NZ9000Deltaalr by double-crossover recombination using temperature-sensitive integration plasmid pG(+)host9 and a food-grade vector pALR with entirely lactococcal DNA elements, including lactococcal replicon, nisin-inducible promoter PnisA and the alr gene from Lactobacillus casei BL23 as a complementation marker. By using the new food-grade host/vector system, the green fluorescent protein and capsid protein of porcine circovirus type II were successfully overexpressed under the nisin induction. These results indicate that this food-grade host/vector expression system has application potential as an excellent antigen delivery vehicle, and is also suitable for the use in the manufacture of ingredients for the food industry. PMID- 22674188 TI - Exposure of the human body to professional and domestic induction cooktops compared to the basic restrictions. AB - We investigated whether domestic and professional induction cooktops comply with the basic restrictions defined by the International Commission on Non-Ionizing Radiation Protection (ICNIRP). Based on magnetic field measurements, a generic numerical model of an induction cooktop was derived in order to model user exposure. The current density induced in the user was simulated for various models and distances. We also determined the exposure of the fetus and of young children. While most measured cooktops comply with the public exposure limits at the distance specified by the International Electrotechnical Commission (standard IEC 62233), the majority exceeds them at closer distances, some of them even the occupational limits. The maximum current density in the tissue of the user significantly exceeds the basic restrictions for the general public, reaching the occupational level. The exposure of the brains of young children reaches the order of magnitude of the limits for the general public. For a generic worst-case cooktop compliant with the measurement standards, the current density exceeds the 1998 ICNIRP basic restrictions by up to 24 dB or a factor of 16. The brain tissue of young children can be overexposed by 6 dB or a factor of 2. The exposure of the tissue of the central nervous system of the fetus can exceed the limits for the general public if the mother is exposed at occupational levels. This demonstrates that the methodology for testing induction cooktops according to IEC 62233 contradicts the basic restrictions. This evaluation will be extended considering PMID- 22674187 TI - Generation and characterization of yeast two-hybrid cDNA libraries derived from two distinct mouse pluripotent cell types. AB - Pluripotent stem cells have the therapeutic potential in future regenerative medicine applications. Therefore, it is highly important to understand the molecular mechanisms governing the pluripotency and differentiation potential of these cells. Our current knowledge of pluripotent cells is largely limited owing to the candidate gene/protein approach rather than studying the complex interactions of the proteins. Experimentally, yeast two-hybrid system (Y2H) is by far the most useful and widely used method to detect the protein-protein interactions in high-throughput screenings. Unfortunately, currently there is no GAL4-based pluripotent stem cell-specific cDNA library available for screening the interaction proteins impeding the large-scale studies. In this study, we report the construction of Y2H cDNA libraries derived from mouse pluripotent embryonic stem cells (ESCs) and multipotent adult germ-line stem cells (maGSCs) in GAL4-based Y2H vector system with very high transformation efficiency. Furthermore, we have constructed two different baits and screened for interaction partners in an effort to characterize the libraries and also as a part of our ongoing studies. Consequently, many putative interaction proteins were identified in both cases and their interaction was further validated by direct-Y2H. The observed interactions between bait proteins and their respective analyzed putative interaction proteins were further confirmed using two independent approaches in mammalian cells, thus highlighting the biological significance of the identified interactor (s). Finally, we would like to make these cDNA libraries as a resource that can be distributed to the research community. PMID- 22674189 TI - Immunoextraction of zinc proteins from human plasma using chicken yolk antibodies immobilized onto paramagnetic particles and their electrophoretic analysis. AB - Zinc(II) as the only transition metal lacking redox activity is an essential part of approximately 10% proteins as a cofactor of these proteins. Considering the fact that there are numerous zinc(II) containing proteins, proteomics and metallomics studies aimed on them require accurate methods for preparation of real biological samples prior to their subsequent analysis using 2DE and MS. For this purpose, we suggested a new method based on chicken anti-zinc antibodies and magnetizable particles. Antibodies were covalently immobilized to the surface of paramagnetic beads activated with tosyl group. Binding of the antibody to the beads was confirmed by secondary anti-chicken antibody conjugated with horseradish peroxidase. The immunoextraction conditions, such as concentration of the beads (6-18 MUg/mL of the sample), time of immunoextraction (6-34 min), pH and composition of the elution buffer, and time of extraction (48-300 s) were optimized. Subsequently, zinc proteins were extracted from human plasma and total concentration of zinc was monitored by electrochemical detection in the extracts. Under optimal conditions it was possible to monitor the proteins and zinc removal from the sample by chip CE, SDS-PAGE, and indirectly using electrochemistry. PMID- 22674190 TI - Mechanisms of cardiotoxicity associated with ErbB2 inhibitors. AB - The ErbB2 receptor is a proto-oncogene associated with a poor prognosis in breast cancer. Herceptin, the only humanized anti-ErbB2 antibody currently in clinical use, has proven to be an essential tool in the immunotherapy of breast carcinoma, but induces cardiotoxicity. ErbB2 is involved in the growth and survival pathway of adult cardiomyocytes; however, its levels in the adult heart are much lower than those found in breast cancer cells, the intended targets of anti-ErbB2 antibodies. Furthermore, clinical trials have shown relatively low cardiotoxicity for Lapatinib, a dual kinase inhibitor of EGFR and ErbB2, and Pertuzumab, a new anti-ErbB2 monoclonal antibody currently in clinical trials, which recognizes an epitope distant from that of Herceptin. A novel human antitumor compact anti ErbB2 antibody, Erb-hcAb, selectively cytotoxic for ErbB2-positive cancer cells in vitro and vivo, recognizes an epitope different from that of Herceptin, and does not show cardiotoxic effects both in vitro on rat and human cardiomyocytes and in vivo on a mouse model. We investigated the molecular basis of the different cardiotoxic effects among the ErbB2 inhibitors by testing their effects on the formation of the Neuregulin 1beta (NRG-1)/ErbB2/ErbB4 complex and on the activation of its downstream signaling. We report herein that Erb-hcAb at difference with Herceptin, 2C4 (Pertuzumab) and Lapatinib, does not affect the ErbB2-ErbB4 signaling pathway activated by NRG-1 in cardiac cells. These findings may have important implications for the mechanism and treatment of anti-ErbB2 induced cardiotoxicity. PMID- 22674191 TI - Goserelin and bicalutamide treatments alter the expression of microRNAs in the prostate. AB - BACKGROUND: Although endocrine therapy has been used for decades, its influence on the expression of microRNAs (miRNAs) in clinical tissue specimens has not been analyzed. Moreover, the effects of the TMPRSS2:ERG fusion on the expression of miRNAs in hormone naive and endocrine-treated prostate cancers are poorly understood. METHODS: We used clinical material from a neoadjuvant trial consisting of 28 men treated with goserelin (n = 8), bicalutamide (n = 9), or no treatment (n = 11) for 3 months prior to radical prostatectomy. Freshly frozen specimens were used for microarray analysis of 723 human miRNAs. Specific miRNA expression in cancer, benign epithelium and stromal tissue compartments was predicted with an in silico Bayesian modeling tool. RESULTS: The expression of 52, 44, and 34 miRNAs was affected >1.4-fold by the endocrine treatment in the cancer, non-malignant epithelium, and stromal compartments, respectively. Of the 52 miRNAs, only 10 were equally affected by the two treatment modalities in the cancer compartment. Twenty-six of the 52 genes (50%) showed AR binding sites in their proximity in either VCaP or LNCaP cell lines. Forty-seven miRNAs were differentially expressed in TMPRSS2:ERG fusion positive compared with fusion negative cases. Endocrine treatment reduced the differences between fusion positive and negative cases. CONCLUSIONS: Goserelin treatment and bicalutamide treatment mostly affected the expression of different miRNAs. The effect clearly varied in different tissue compartments. TMPRSS2:ERG fusion positive and negative cases showed differential expression of miRNAs, and the difference was diminished by androgen ablation. PMID- 22674192 TI - Thoracolumbar fracture reduction by percutaneous in situ contouring. AB - PURPOSE: Percutaneous in situ contouring is based on bilateral bending of rods on the spine, thus increasing lordosis at the fracture. It was analyzed if this technique would provide a better reduction than prone positioning and how sagittal alignment would behave. METHODS: Twenty-nine patients were operated using in situ contouring and selective anterior fusion for non-neurologic A2, A3 or B2 fractures. Clinical results were assessed prospectively using visual analog scale (VAS) and Oswestry Disability Index (ODI). The radiographic deformity correction was measured by sagittal index and regional kyphosis. Sagittal balance was assessed using kyphosis, lordosis, T9 tilt, pelvic incidence, pelvic tilt and sacral slope. Posterior wall fragment reduction was evaluated by computed tomography. RESULTS: After 2 years, VAS and ODI were comparable to the status prior to the accident. The sagittal index was 19.7 degrees preoperatively, 5.3 degrees after prone positioning and -1.1 degrees after in situ contouring (p < 0.001). The loss of correction was 2.4 degrees , mainly during the first 3 months. Similar observations were made for regional kyphosis. The sagittal spino pelvic alignment was stable postoperatively. A preoperative canal obstruction >=50 % was observed in 16 patients, and the fragments migrated anteriorly in all patients. CONCLUSIONS: Percutaneous instrumentation and anterior fusion provides good clinical results. In situ contouring increases lordosis obtained by prone positioning. Anterior column lengthening and ligamentotaxis reduce posterior wall fragments, which decompress the canal without laminectomy. The fusion of anterior defects prevents the loss of correction and provides a stable sagittal profile. The instrumentation may be removed without damaging the paravertebral muscles and loss of correction. PMID- 22674193 TI - Unusual association of intraspinal extramedullary teratoma with congenital scoliosis in an elderly adult: case report and literature review. AB - INTRODUCTION: Intraspinal teratomas associated with congenital scoliosis are extremely rare, especially in an elderly adult. MATERIALS AND METHODS: We report the seventh case of intraspinal extramedullary teratoma coexisting with congenital scoliosis in a patient older than 50 years, possibly the oldest patient documented in literature. A 56-year-old male suffered from low back pain that increased with calf numbness and foot weakness. Conventional radiography showed a congenital scoliosis due to incomplete segmentation of the L2 and L4 vertebras, and magnetic resonance images revealed a heterogeneous intraspinal extramedullary mass located at L4-S1. RESULTS: The tumor was totally removed, and was confirmed as a mature teratoma on biopsy. The patient remains asymptomatic at 34-month follow-up. CONCLUSIONS: Rare intraspinal teratoma should be included in the differential diagnosis of intraspinal mass, especially in patient with congenital scoliosis. Patient with mature teratoma may survive with out any symptoms in the long term. Progressing neurological deficit is a main indication for surgery. Excellent clinical outcomes could be achieved by surgical resection and dural sac decompression. PMID- 22674194 TI - Kinetic magnetic resonance imaging analysis of lumbar segmental mobility in patients without significant spondylosis. AB - PURPOSE: The purpose of this study was to examine lumbar segmental mobility using kinetic magnetic resonance imaging (MRI) in patients with minimal lumbar spondylosis. METHODS: Mid-sagittal images of patients who underwent weight bearing, multi-position kinetic MRI for symptomatic low back pain or radiculopathy were reviewed. Only patients with a Pfirrmann grade of I or II, indicating minimal disc disease, in all lumbar discs from L1-2 to L5-S1 were included for further analysis. Translational and angular motion was measured at each motion segment. RESULTS: The mean translational motion of the lumbar spine at each level was 1.38 mm at L1-L2, 1.41 mm at L2-L3, 1.14 mm at L3-L4, 1.10 mm at L4-L5 and 1.01 mm at L5-S1. Translational motion at L1-L2 and L2-L3 was significantly greater than L3-4, L4-L5 and L5-S1 levels (P < 0.007). The mean angular motion at each level was 7.34 degrees at L1-L2, 8.56 degrees at L2-L3, 8.34 degrees at L3-L4, 8.87 degrees at L4-L5, and 5.87 degrees at L5-S1. The L5-S1 segment had significantly less angular motion when compared to all other levels (P < 0.006). The mean percentage contribution of each level to the total angular mobility of the lumbar spine was highest at L2-L3 (22.45 %) and least at L5/S1 (14.71 %) (P < 0.001). CONCLUSION: In the current study, we evaluated lumbar segmental mobility in patients without significant degenerative disc disease and found that translational motion was greatest in the proximal lumbar levels whereas angular motion was similar in the mid-lumbar levels but decreased at L1-L2 and L5-S1. PMID- 22674195 TI - A microRNA expression signature predicts meningioma recurrence. AB - The aberrant expression of microRNAs (miRNAs) is associated with a variety of diseases, including cancer. In our study, we examined the miRNA expression profile of meningiomas, which is a common type of benign intracranial tumor derived from the protective meninges membranes that surround the brain and spinal cord. To define a typical human meningioma miRNA profile, the expression of 200 miRNAs in a training sample set were screened using quantitative reverse transcription polymerase chain reaction analysis, and then significantly altered miRNAs were validated in a secondary independent sample set. Kaplan-Meier and univariate/multivariate Cox proportional hazard regression analyses were performed to assess whether miRNA expression could predict the recurrence of meningioma after tumor resection. After a two-phase selection and validation process, 14 miRNAs were found to exhibit significantly different expression profiles in meningioma samples compared to normal adjacent tissue (NAT) samples. Unsupervised clustering analysis indicated that the 14-miRNA profile differed between tumor and NAT samples. Downregulation of miR-29c-3p and miR-219-5p were found to be associated with advanced clinical stages of meningioma. Kaplan-Meier analysis showed that high expression of miR-190a and low expression of miR-29c-3p and miR-219-5p correlated significantly with higher recurrence rates in meningioma patients. Cox proportional hazard regression analysis revealed that miR-190a expression level is an important prognostic predictor that is independent of other clinicopathological factors. Our results suggest that the use of miRNA profiling has significant potential as an effective diagnostic and prognostic marker in defining the expression signature of meningiomas and in predicting postsurgical outcomes. PMID- 22674196 TI - Clinical Images: ultrasonographic appearance of thyroid acropachy. PMID- 22674197 TI - Interleukin-1beta induces differentiation of human mesenchymal stem cells into osteoblasts via the Wnt-5a/receptor tyrosine kinase-like orphan receptor 2 pathway. AB - OBJECTIVE: Mesenchymal stem cells (MSCs) are considered to be a novel tool for the treatment of rheumatoid arthritis (RA) because of their multipotency to differentiate into osteoblasts and chondrocytes, their immunosuppressive effects, and availability. The aim of this study was to assess the mechanisms of human MSC differentiation into osteoblasts under inflammatory conditions. METHODS: Human MSCs were cultured in commercialized osteogenic induction medium with inflammatory cytokines for up to 10 days. Osteoblast differentiation was detected by alkaline phosphatase staining and messenger RNA (mRNA) expression of multiple osteoblast markers. Mineralization was assessed by alizarin red S staining. RESULTS: Among the various cytokines tested, interleukin-1beta (IL-1beta) induced differentiation of human MSCs into osteoblasts, which was confirmed by alkaline phosphatase activity, expression of RUNX2 mRNA, and strong alizarin red S staining. Among various molecules of the Wnt family, Wnt-5a and receptor tyrosine kinase-like orphan receptor 2 (Ror2), a major receptor of Wnt-5a, were significantly induced in human MSCs by IL-1beta. Silencing of either WNT5A or ROR2 by small interfering RNA with 2 different sequences reduced alkaline phosphatase activity, RUNX2 expression, and alizarin red S staining of human MSCs induced by IL-1beta. CONCLUSION: IL-1beta effectively and rapidly induced human MSC differentiation into osteoblasts and mineralization, mainly through the noncanonical Wnt-5a/Ror2 pathway. These results suggest potential benefits of IL 1beta-treated human MSCs in the treatment of damaged bone as well as in the induction of self-renewal and self-repair of damaged tissue, including osseous tissue. PMID- 22674198 TI - Two phase 2 trials of the novel Akt inhibitor perifosine in patients with advanced renal cell carcinoma after progression on vascular endothelial growth factor-targeted therapy. AB - BACKGROUND: The clinical activity of allosteric inhibitors of mammalian target of rapamycin (mTOR) inhibitors in renal cell carcinoma (RCC) may be limited by upstream activation of phosphatidylinositol 3 (PI3)-kinase/Akt resulting from mTOR1 inhibition. On the basis of this rationale, 2 independent phase 2 trials (Perifosine 228 and 231) were conducted to assess the efficacy and safety of the novel Akt inhibitor perifosine in patients with advanced RCC who had failed on previous vascular endothelial growth factor (VEGF)-targeted therapy. METHODS: In the Perifosine 228 trial, 24 patients with advanced RCC received oral perifosine (100 mg daily). Perifosine 231 enrolled 2 groups that received daily oral perifosine (100 mg daily): Group A comprised 32 patients who had received no prior mTOR inhibitor, and Group B comprised 18 patients who had received 1 prior mTOR inhibitor. RESULTS: In the Perifosine 228 trial, 1 patient achieved a partial response (objective response rate, 4%; 95% confidence interval, 0.7% 20%), and 11 patients (46%) had stable disease as their best response. The median progression-free survival was 14.2 weeks (95% confidence interval, 7.7-21.6 weeks). In the Perifosine 231 trial, 5 patients achieved a partial response (objective response rate, 10%; 95% confidence interval, 4.5%-22.2%) and 16 patients (32%) had stable disease as their best response. The median progression free survival was 14 weeks (95% confidence interval, 12.9, 20.7 weeks). Overall, perifosine was well tolerated, and there were very few grade 3 and 4 events. The most common toxicities included nausea, diarrhea, musculoskeletal pain, and fatigue. CONCLUSIONS: Although perifosine demonstrated activity in patients with advanced RCC after failure on VEGF-targeted therapy, its activity was not superior to currently available second-line agents. Nonetheless, perifosine may be worthy of further study in RCC in combination with other currently available therapies. PMID- 22674199 TI - Fractal network dimension and viscoelastic powerlaw behavior: II. An experimental study of structure-mimicking phantoms by magnetic resonance elastography. AB - The dynamics of the complex shear modulus, G*, of soft biological tissue is governed by the rigidity and topology of multiscale mechanical networks. Multifrequency elastography can measure the frequency dependence of G* in soft biological tissue, providing information about the structure of tissue networks at multiple scales. In this study, the viscoelastic properties of structure mimicking phantoms containing tangled paper stripes embedded in agarose gel are investigated by multifrequency magnetic resonance elastography within the dynamic range of 40-120 Hz. The effective media viscoelastic properties are analyzed in terms of the storage modulus (the real part of G*), the loss modulus (the imaginary part of G*) and the viscoelastic powerlaw given by the two-parameter springpot model. Furthermore, diffusion tensor imaging is used for investigating the effect of network structures on water mobility. The following observations were made: the random paper networks with fractal dimensions between 2.481 and 2.755 had no or minor effects on the storage modulus, whereas the loss modulus was significantly increased about 2.2 kPa per fractal dimension unit (R = 0.962, P < 0.01). This structural sensitivity of the loss modulus was significantly correlated with the springpot powerlaw exponent (0.965, P < 0.01), while for the springpot elasticity modulus, a trend was discernable (0.895, P < 0.05). No effect of the paper network on water diffusion was observed. The gel phantoms with embedded paper stripes presented here are a feasible way for experimentally studying the effect of network topology on soft-tissue viscoelastic parameters. In the dynamic range of in vivo elastography, the fractal network dimension primarily correlates to the loss behavior of soft tissue as can be seen from the loss modulus or the powerlaw exponent of the springpot model. These findings represent the experimental underpinning of structure-sensitive elastography for an improved characterization of various soft-tissue diseases. PMID- 22674200 TI - Does this woman have adnexal torsion? AB - BACKGROUND: No questionnaire is currently available for the presurgical diagnosis of adnexal torsion (AT). Our objective was to develop a predictive model for AT, based on the Self Assessment Questionnaire for Gynecologic Emergencies (SAQ-GE) designed for triaging women with acute pelvic pain. METHODS: We performed a multicenter prospective trial conducted in five hospitals in France. Four hundred and ninety-six (496) women with acute pelvic pain (Numeric Rating Scale>4), including 31 with AT, were recruited from September 2006 through April 2008. An AT score was built using the SAQ-GE. RESULTS: Five criteria were independently associated with AT confirmed by surgery: unilateral lumbar or abdominal pain [adjusted diagnostic odds ratio (aDOR), 23.3; 95% confidence interval (95% CI), 3.0-178]; absence of leucorrhea and metrorrhagia (aDOR, 7.0; 95% CI, 2.5-20), ovarian pain (aDOR, 5.5; 95% CI, 1.5-21), unbearable pain (aDOR, 5.0; 95% CI, 1.4 18) and vomiting (aDOR, 3.7; 95% CI, 1.6-9.0). The SAQ-GE torsion score was based on these five criteria and its values range from 0 to 10. The low-risk group (SAQ GE torsion score<7), based on the score values, has a sensitivity (Se) of 96.7% (95% CI, 90.5-100), a negative predictive value of 99.7% (95% CI, 99.1-100) and a negative likelihood ratio (Lr-) of 0.05, ruling out AT with a probability of AT of 0.3% (95% CI, 0.0-0.9). Cross-validation of the model was performed using the jackknife resampling procedure, retrieving an unbiased Se of 87.1 (95% CI, 75.1 99.1) and a specificity of 74.2% (95% CI, 70.2-78.2). CONCLUSIONS: The SAQ-GE torsion score may prove useful for screening for AT in patients experiencing acute pelvic pain. PMID- 22674201 TI - Rationale of first-line endoscopy-based fertility exploration using transvaginal hydrolaparoscopy and minihysteroscopy. AB - The transvaginal access for exploration of tubo-ovarian function in women with unexplained infertility has been revived since transvaginal hydrolaparoscopy (THL) was introduced in 1998. One prospective double-blind trial and several reviews have validated the diagnostic value of THL in comparison with laparoscopy for the exploration of women with unexplained infertility. A review of the recent literature confirms the efficacy and safety of the technique for first-line endoscopy-based exploration of fertility. The standard policy of 1-year delay for laparoscopic investigation in unexplained infertility is challenged. In older women and particularly in women experienced in fertility awareness methods, THL and minihysteroscopy can be performed after a waiting period of 6-12 months. PMID- 22674202 TI - Characterization of the insulin-like growth factor axis in term pregnancies complicated by maternal obesity. AB - STUDY QUESTION: Does maternal obesity affect insulin-like growth factor (IGF) axis protein expression patterns in maternal and cord blood? SUMMARY ANSWER: Maternal obesity attenuates cord blood expression of IGF-binding protein (IGFBP) 4. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: The IGF axis plays a critical role in fetal growth and development. Maternal obesity compromises IGF axis protein expression in fetal circulation, which is consistent with the findings of epidemiological studies suggesting that maternal obesity has an independent effect on fetal growth signals during in utero development. STUDY DESIGN: This cross-sectional case-control study involved 12 lean [body mass index (BMI) 18.5 24.9 kg/m2] and 12 obese (BMI>=30 kg/m2) women and their neonates at term. At the completion of the study, IGF axis protein expression and hormone concentrations in both maternal and cord blood were examined. PARTICIPANTS AND SETTING: We obtained fasting serum samples from cases and controls matched for age, gestation, mode of delivery, parity and glucose tolerance prior to and immediately following elective caesarean section. The corresponding umbilical cord blood was also collected at birth. MAIN RESULTS AND THE ROLE OF CHANCE: Between-group comparisons revealed elevated maternal insulin (P=0.03) and leptin (P<0.01) concentrations in obese gravidas. After adjustment, the maternal homeostasis model of assessment-insulin resistance (HOMA-IR) score was positively correlated with both maternal BMI and leptin levels (P<0.01). Umbilical cord blood levels of IGFBP-3 showed an inverse trend to maternal HOMA-IR (P=0.03) but were directly related to the fetal-placental weight ratio (P<0.01). In cord serum from obese mothers, IGFBP-4 expression was attenuated compared with the controls (P<0.05). LIMITATIONS: The limitations of our study include the cross-sectional design and relatively small sample size. WIDER IMPLICATIONS: Our results provide preliminary evidence for the applicability of our findings to other ethnic groups when pregnancy is complicated by obesity. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the University of Ottawa, Faculty of Health Sciences/Children's Hospital of Eastern Ontario Research Partnership Grant awarded to K.B.A. and Z.M.F. The authors have no conflicts of interest to declare. PMID- 22674203 TI - Lesion kinetics in a non-human primate model of endometriosis. AB - BACKGROUND: Endometriosis is a common cause of pelvic pain and infertility in women of reproductive age. It is characterized by the presence of endometrial tissue outside the normal location, predominantly in the pelvic peritoneum causing severe abdominal pain. However, the severity of the symptoms of endometriosis does not always correlate with the anatomic severity of the disease. This lack of correlation may be due to morphological lesion variation during disease progression. This study examined lesion kinetics in a non-human primate model of endometriosis to better understand lesion dynamics. METHODS: Endometriosis was experimentally induced in nine normal cycling female adult olive baboons (Papio anubis) by i.p. inoculation of autologous menstrual endometrium on Day 2 of menses for two consecutive menstrual cycles. Diagnostic laparoscopies were performed between Day 8-12 post-ovulation at 1, 3, 6, 9 and 12 months, followed by a necropsy at 15 months, after the second inoculation. In two animals, lesions were excised/ablated at 6 months and they were monitored for lesion recurrence and morphological changes by serial laparoscopy. Furthermore, five control animals underwent surgeries conducted at the same time points but without inoculation. RESULTS: A total of 542 endometriotic lesions were observed. The location, macroscopic (different colours) and microscopic appearance confirmed distinct endometriosis pathology in line with human disease. The majority of the lesions found 1 month after tissue inoculation were red lesions, which frequently changed colour during the disease progression. In contrast, blue lesions remained consistently blue while white lesions were evident at the later stages of the disease process and often regressed. There were significantly lower numbers of powder burn, blister and multicoloured lesions observed per animal in comparison to black and blue lesions (P-value<=0.05). New lesions were continually arising and persisted up to 15 months post-inoculation. Lesions reoccurred as early as 3 months after removal and 69% of lesions excised/ablated had reoccurred 9 months later. Interestingly, endometriotic lesions were also found in the non-inoculated animals, starting at the 6-month time point following multiple surgeries. CONCLUSIONS: Documentation of lesion turnover in baboons indicated that lesions changed their colour from red to white over time. Different lesion types underwent metamorphosis at different rates. A classification of lesions based on morphological appearance may help disease prognosis and examination of the effect of the lesion on disease symptoms, and provide new opportunities for targeted therapies in order to prevent or treat endometriosis. Surgical removal of endometriotic lesions resulted in a high incidence of recurrence. Spontaneous endometriosis developed in control baboons in the absence of inoculation suggesting that repetitive surgical procedures alone can induce the spontaneous evolution of the chronic disease. Although lesion excision/ablation may have short-term benefits (e.g. prior to an IVF cycle in subfertile women), for long-term relief of symptoms perhaps medical therapy is more effective than surgical therapy. PMID- 22674204 TI - Apolipoprotein A-I and B levels, dyslipidemia and metabolic syndrome in south west Chinese women with PCOS. AB - STUDY QUESTION: What are the relationships between apolipoprotein (apo) A-I and apoB concentrations, the apoB/apoA-I ratio and the prevalences of dyslipidemia and metabolic syndrome (MS) in south-west Chinese women with polycystic ovary syndrome (PCOS). SUMMARY ANSWER: There is a relatively high incidence of dyslipidemia and MS in south-west Chinese women with PCOS, especially in patients without hyperandrogenism. Patients with dyslipidemia are more obese, and have a more adverse glucose and lipid metabolic profile and higher apoB levels and apoB/apoA-I ratio. The increased apoB levels and apoB/A1 ratio and the MS are strongly associated with PCOS, suggesting that there is an increased risk of cardiovascular diseases in these patients. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Dyslipidemia and MS have been widely studied in women with PCOS, but to date no data from south-west Chinese subjects have been available. The apoB/apoA I ratio has been reported to be strongly associated with MS and insulin resistance (IR) and to be a reliable parameter that reflects lipid disturbances and the potential to develop atherosclerosis, but its relationship with PCOS is unclear. DESIGN This case-control study included 406 patients with PCOS and 342 control women between 17 and 40 years of age from a population in south-west China during 2006-2011. PARTICIPANTS AND SETTING: The diagnosis of PCOS was based on the revised 2003 Rotterdam criteria. The control group, consisting of women with infertility due to a Fallopian obstruction or the husband's infertility, women undergoing a pre-pregnancy check and healthy volunteers, was recruited from the same hospital during the same period. All women were not taking any medication known to affect carbohydrate or lipid or hormone metabolism for at least 3 months prior to the study, and were studied during the follicular phase of their menstrual cycle. MS was assessed by the National Cholesterol Education Program-Adult treatment Panel (NCEP-ATP) III criteria modified for Asian populations. Dyslipidemia was defined by one or more of the following conditions: fasting total cholesterol>=5.7 mmol/l, fasting triglycerides (TG)>=1.7 mmol/l, fasting high-density lipoprotein cholesterol (HDL-C)<1.29 mmol/l or fasting low density lipoprotein cholesterol (LDL-C)>=3.6 mmol/l. MAIN RESULTS AND THE ROLE OF CHANCE: The prevalence of dyslipidemia in patients with PCOS was 52.96%, about two times than that in the controls, 28.95%. The most common components of dyslipidemia in patients with PCOS were decreased HDL-C (41.13%) and increased TG (24.14%). PCOS patients with dyslipidemia had significantly higher TG/HDL-C ratios, and lower HDL-C and apoA-I levels when compared with the controls or patients without dyslipidemia, and had significantly higher BMIs, fasting insulin concentrations, 2-h insulin and glucose levels, homeostatic model assessment IR, TG levels, LDL-C levels, atherogenic indexes, apoB concentrations and apoB/apoA-I ratios when compared with all of the control women, with or without dyslipidemia and patients without dyslipidemia. The frequency of MS in patients with PCOS was 25.62%, more than five times than that in the controls. The main two risk factors were increased waist circumference and low HDL-C levels. In the four PCOS phenotypes based on the Rotterdam criteria, the oligo- and/or anovulation+PCO presented the highest prevalence of dyslipidemia (66.14%) and MS (34.65%). Binary logistic regression analysis showed that increased apoB levels, an increased apoB/apoA-I ratio and MS was strongly associated with PCOS (odds ratio=17.41, 27.16 and 7.66, 95% confidence interval: 6.93-43.74, 9.46-77.93 and 4.32-13.57, respectively) after adjustment for age. BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION: The relatively minor limitations of this study are discussed within the paper. GENERALISABILITY TO OTHER POPULATIONS: The metabolic patterns found in south-west Chinese with PCOS are compared with that of other populations. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by Chinese National Natural Science Foundation (81070463), Program for Changjiang Scholars and Innovative Research Team in University (IRT0935), and Research Seed Fund from West China Second Hospital of Sichuan University (to H.B.). There are no any competing interests. TRIAL REGISTRATION NUMBER: N/A. PMID- 22674205 TI - Quantification of anti-Mullerian hormone (AMH) in dried blood spots: validation of a minimally invasive method for assessing ovarian reserve. AB - BACKGROUND: Biological markers of ovarian reserve have the potential to advance research on fecundability, infertility and reproductive aging. Anti-Mullerian hormone (AMH) has emerged as a clinically useful measure of ovarian reserve, but the requirement for venous blood is an obstacle to application in non-clinical settings. This paper validates a new method for quantifying AMH in dried blood spot (DBS) samples--drops of whole blood collected on filter paper following a simple finger stick. METHODS: Matched serum and DBS samples were obtained from n=101 women of reproductive age, and AMH values were compared using regression analyses and scatter plots. The precision, reliability, linearity, recovery and lower detection limit of the DBS assay were evaluated, as well as the stability of AMH in DBS across a range of storage conditions. RESULTS: There was a strong agreement between AMH concentrations measured in DBS and serum samples across the entire assay range. Analysis of within-assay (percent coefficient of variation, 4.7-6.5%) and between-assay (3.5-7.2%) variability indicated a high level of assay precision and reliability, respectively. The minimum detectable dose of AMH was 0.065 ng/ml. Concentrations of AMH remained stable in DBS samples stored for 2 weeks at room temperature, and for 4 weeks when refrigerated. CONCLUSIONS: The DBS assay performs at a level that is comparable to serum-based methods, with the advantage of lower burdens and costs associated with blood collection that may be advantageous for research in clinical as well as non-clinical settings on the causes and consequences of variation in ovarian reserve. PMID- 22674206 TI - The current fertility preservation consultation model: are we adequately informing cancer patients of their options? AB - BACKGROUND: There is very limited information about the amount of information that cancer patients retain after a fertility preservation (FP) consultation (FPC). Our objective was to assess patients' knowledge following FPC and to examine predictors of increased knowledge. METHODS: We conducted a multi-center, cross-sectional, web-based survey at academic IVF centers, including women aged 18-43 years seen for comprehensive FPC between April 2009 and December 2010. The primary outcome measure was a knowledge score designed to assess comprehension of FP options. Analysis was performed to assess which patient variables were associated with higher knowledge scores. A 13-item knowledge tool about FP was developed (Kuder-Richardson 20=0.64). RESULT(S): Among 90 eligible subjects, 66 were successfully contacted and 52 completed the survey (79% response rate). Participant's median age was 30.7 (interquartile range (IQR) 24.9-36.9) years and most were Caucasian, college graduates, nulliparous and in a committed relationship. The median knowledge post-FPC score was 6 (IQR: 5-9). Higher knowledge scores were associated with a college education, higher income, a primary diagnosis of breast cancer, additional contact with the FP specialist following the initial FPC and use of specific reference websites such as www.fertilehope.org. Parity, marital status and completion of FP treatment were not associated with knowledge scores. CONCLUSIONS: FP knowledge following comprehensive FPC remains limited. Modifications to the current single visit FPC, such as a standard follow-up visit or additional educational tools, may be needed to improve patient comprehension of complex FP treatment options. Further research is needed to validate the knowledge scale in broader populations of cancer patients receiving FPC. PMID- 22674207 TI - Characterization of DNA methylation errors in patients with imprinting disorders conceived by assisted reproduction technologies. AB - BACKGROUND: There is an increased incidence of rare imprinting disorders associated with assisted reproduction technologies (ARTs). The identification of epigenetic changes at imprinted loci in ART infants has led to the suggestion that the techniques themselves may predispose embryos to acquire imprinting errors and diseases. However, it is still unknown at what point(s) these imprinting errors arise, or the risk factors. METHODS: In 2009 we conducted a Japanese nationwide epidemiological study of four well-known imprinting diseases to determine any association with ART. Using bisulfite sequencing, we examine the DNA methylation status of 22 gametic differentially methylated regions (gDMRs) located within the known imprinted loci in patients with Beckwith-Wiedemann syndrome (BWS, n=1) and also Silver-Russell syndrome (SRS, n= 5) born after ART, and compared these with patients conceived naturally. RESULTS: We found a 10-fold increased frequency of BWS and SRS associated with ART. The majority of ART cases showed aberrant DNA methylation patterns at multiple imprinted loci both maternal and paternal gDMRs (5/6), with both hyper- and hypomethylation events (5/6) and also mosaic methylation errors (5/6). Although our study may have been limited by a small sample number, the fact that many of the changes were mosaic suggested that they occurred after fertilization. In contrast, few of the patients who were conceived naturally exhibited a similar pattern of mosaic alterations. The differences in methylation patterns between the patients who were conceived naturally or after ART did not manifest due to the differences in the disease phenotypes in these imprinting disorders. CONCLUSION: A possible association between ART and BWS/SRS was found, and we observed a more widespread disruption of genomic imprints after ART. The increased frequency of imprinting disorders after ART is perhaps not surprising given the major epigenetic events that take place during early development at a time when the epigenome is most vulnerable. PMID- 22674208 TI - Synthesis and evaluation of novel glass ceramics as drug delivery systems in osteomyelitis. AB - In this study, a new generation of bioactive glass ceramics were developed using the wet chemical method. The synthetic conditions were strictly controlled to obtain the materials of a nanometric scale. As evaluated by scanning electron microscopy, bone-like apatite layers were produced in large amounts and completely covered their surfaces after immersion in phosphate buffer saline. On the basis of X-ray diffraction, X-ray fluorescence, and Fourier transform infrared spectroscopy results, PO43- groups of hydroxyapatite (HA) were partially substituted by SiO44- species. The defective chemical structures introduced provided materials that were more biologically active, compared with the parent HA. For effective treatment of infected bones, scaffolds containing the bioactive ceramics were prepared by chitosan cross-linking, and loaded with vancomycin (VCM). The drug-loaded scaffolds were not toxic to bone cells. About 75%-80% of the entrapped drug was released in a controlled pattern and the release was sustained over a 12-day period. The concentration of drug released was determined to be above 20 times the half maximal effective concentration of VCM on Staphylococcus aureus, and was sufficient for killing bacteria growing as biofilm. In summary, the synthesized bioceramics exhibited many of properties associated with an ideal material for implantable drug delivery system, and were suitable for testing the ability to cure bone diseases including osteomyelitis. PMID- 22674209 TI - Self assembled composites of luminescent Ru(II) metallopolymers and the Dawson polyoxometalate alpha-[Mo18O54(SO4)2]4-. AB - The interaction of two luminescent metallopolymers; [Ru(bpy)(2)(PVP)(10)](2+) and [Ru(bpy)(2)(CAIP)co-poly(7)](+), where bpy is 2,2'-bipyridyl, PVP is polyvinylpyridine, and (CAIP)co-poly(7) is poly(styrene(6)-co-p (aminomethyl)styrene) amide linked to 2-(4-carboxyphenyl)imidazo[4,5-f] [1,10]phenanthroline, with the Dawson polyoxomolybdate alpha [Mo(18)O(54)(SO(4))(2)](4-) is described. Both metallopolymers undergo electrostatic association with the polyoxometalate. From both electronic and luminescence spectroscopy the thermodynamic products were determined to be {[Ru(bpy)(2)(PVP)(10)](4.5)[Mo(18)O(54)(SO(4))(2)]}(5+) and {[Ru(bpy)(2)(CAIP)co poly(7)](5)[Mo(18)O(54)(SO(4))(2)]}(+), i.e. in both instances, the number of ruthenium centres in the cluster exceeds the number required for charge neutralization of the molybdate centre. Association quenches the luminescence of the metallopolymer although, consistent with the excess of Ru(ii) present in the associated composites, emission is not completely extinguished even when a large excess of [Mo(18)O(54)(SO(4))(2)](4-) is present. The observed emission lifetime was not affected by [Mo(18)O(54)(SO(4))(2)](4-) therefore quenching was deemed static. The luminescent intensity data was found to fit best to a (sphere of action) Perrin model from which the radii of the quenching were calculated as 4.6 A and 5.8 A for [Ru(bpy)(2)(PVP)(10)](2+) and [Ru(bpy)(2)(CAIP co-poly)(7)](+) respectively. Both UV/Vis and resonance Raman data indicate the presence of a new optical transition centered around 490 nm for the composite, {[Ru(bpy)(2)(PVP)(10)](4.5)[Mo(18)O(54)(SO(4))(2)]}(5+) but not for {[Ru(bpy)(2)(CAIP)co-poly(7)](5)[Mo(18)O(54)(SO(4))(2)]}(+). This indicates strong electronic interaction between the metal centres in the former composite, which despite good thermodynamic analogy, is not observed for {[Ru(bpy)(2)(CAIP)co-poly(7)](5)[Mo(18)O(54)(SO(4))(2)]}(+). These results are consistent with photoelectrochemical studies of layer by layer assemblies of these films which indicate that the ruthenium centre sensitizes polyoxometalate photo-oxidation of benzyl alcohol in {[Ru(bpy)(2)(PVP)(10)](4.5)[Mo(18)O(54)(SO(4))(2)]}(5+) but not in {[Ru(bpy)(2)(CAIP)co-poly(7)](5)[Mo(18)O(54)(SO(4))(2)]}(+). PMID- 22674211 TI - Medical management of Cushing's disease: what is the future? AB - Cushing's disease (CD) is caused by a corticotroph, adrenocorticotropic-hormone (ACTH)-secreting pituitary adenoma resulting in significant morbidity and mortality. Transsphenoidal surgery is the initial treatment of choice in almost all cases. Remission rates for microadenomas are good at 65-90 % (with an experienced neurosurgeon) but remission rates are much lower for macroadenomas. However, even after postoperative remission, recurrence rates are high and can be seen up to decades after an initial diagnosis. Repeat surgery or radiation can be useful in these cases, although both have clear limitations with respect to efficacy and/or side effects. Hence, there is a clear unmet need for an effective medical treatment. Currently, most drugs act by inhibiting steroidogenesis in the adrenal glands. Most is known about the effects of ketoconazole and metyrapone. While effective, access to ketoconazole and metyrapone is limited in many countries, experience with long-term use is limited, and side effects can be significant. Recent studies have suggested a role for a pituitary-directed therapy with new multireceptor ligand somatostatin analogs (e.g., pasireotide, recently approved in Europe for treatment of CD), second-generation dopamine agonists, or a combination of both. Mifepristone (a glucocorticoid receptor antagonist) is another promising drug, recently approved by the FDA for treatment of hyperglycemia associated with Cushing's syndrome. We review available medical treatments for CD with a focus on the two most recent compounds referenced above. Our aim is to expand awareness of current research, and the possibilities afforded by available medical treatments for this mesmerizing, but often frightful disease. PMID- 22674212 TI - Long-term follow-up of a spontaneously improving patient with junctional epidermolysis bullosa associated with ITGB4 c.3977-19T>A splicing mutation. PMID- 22674213 TI - No effects of a single 3G UMTS mobile phone exposure on spontaneous EEG activity, ERP correlates, and automatic deviance detection. AB - Potential effects of a 30 min exposure to third generation (3G) Universal Mobile Telecommunications System (UMTS) mobile phone-like electromagnetic fields (EMFs) were investigated on human brain electrical activity in two experiments. In the first experiment, spontaneous electroencephalography (sEEG) was analyzed (n = 17); in the second experiment, auditory event-related potentials (ERPs) and automatic deviance detection processes reflected by mismatch negativity (MMN) were investigated in a passive oddball paradigm (n = 26). Both sEEG and ERP experiments followed a double-blind protocol where subjects were exposed to either genuine or sham irradiation in two separate sessions. In both experiments, electroencephalograms (EEG) were recorded at midline electrode sites before and after exposure while subjects were watching a silent documentary. Spectral power of sEEG data was analyzed in the delta, theta, alpha, and beta frequency bands. In the ERP experiment, subjects were presented with a random series of standard (90%) and frequency-deviant (10%) tones in a passive binaural oddball paradigm. The amplitude and latency of the P50, N100, P200, MMN, and P3a components were analyzed. We found no measurable effects of a 30 min 3G mobile phone irradiation on the EEG spectral power in any frequency band studied. Also, we found no significant effects of EMF irradiation on the amplitude and latency of any of the ERP components. In summary, the present results do not support the notion that a 30 min unilateral 3G EMF exposure interferes with human sEEG activity, auditory evoked potentials or automatic deviance detection indexed by MMN. PMID- 22674215 TI - Enantio- and diastereoselective hetero-Diels-Alder reactions between 2-aza-3 silyloxy-1,3-butadienes and aldehydes catalyzed by chiral dirhodium(II) carboxamidates. AB - The first catalytic asymmetric hetero-Diels-Alder reaction between 2-aza-3 silyloxy-1,3-butadienes and aldehydes is described. With dirhodium(II) tetrakis[N benzene-fused-phthaloyl-(S)-piperidinonate], Rh(2)(S-BPTPI)(4), the cycloaddition reaction proceeded exclusively in an endo mode to give all-cis-substituted 1,3 oxazinan-4-ones in high yields with up to 98% ee. PMID- 22674214 TI - Rational basis for the combination of PCA3 and TMPRSS2:ERG gene fusion for prostate cancer diagnosis. AB - BACKGROUND: The prostate cancer gene 3 (PCA3) and TMPRSS2:ERG gene fusion are promising prostate cancer (PCa) specific biomarkers. Our aim was to simultaneously quantify the expression levels of PCA3 and TMPRSS2:ERG in a panel of benign prostatic hyperplasia (BPH), normal prostate adjacent to PCa (NP) and PCa tissue samples, to provide a rational basis for the understanding of the false-positive and false-negative results of the urine assays. METHODS: The tissue samples were carefully histopathologically characterized to obtain homogeneous groups. The mRNA was isolated, transcribed into cDNA and the relative expressions of PCA3 and TMPRSS2:ERG were measured using a quantitative real-time polymerase chain reaction. The expression levels of PCA3 and TMPRSS2:ERG were compared between the different groups. RESULTS: We included 48 BPH, 32 NP, and 48 PCa. The PCA3 expression levels progressively increased from BPH to NP (3 times) and finally to PCa (30 times). There were one false-positive sample and seven false-negative samples. The TMPRSS2:ERG gene fusion was found in 8.3% of the BPH, 15.6% of the NP, and 50% of the PCa samples. The use of TMPRSS2:ERG in the PCA3 negative cases allowed diagnosis of four of the seven false-negative samples and added one false-positive, but we had to define a cut-off value to avoid eight false-positive results. CONCLUSIONS: Considering tissue expression of the markers, most of the false-negative results of the PCA3 test were corrected by TMPRSS2:ERG (57%) and the combination of both had a higher sensitivity for PCa diagnosis. Some of the control samples did express TMPRSS2:ERG and a cut-off value had to be defined to avoid false-positive results. PMID- 22674216 TI - Environmental analysis of the logistics of agricultural products from roof top greenhouses in Mediterranean urban areas. AB - BACKGROUND: As urban populations increase so does the amount of food transported to cities worldwide, and innovative agro-urban systems are being developed to integrate agricultural production into buildings; for example, by using roof top greenhouses (RTGs). This paper aims to quantify and compare, through a life cycle assessment, the environmental impact of the current linear supply system with a RTG system by using a case study for the production of tomatoes. RESULTS: The main results indicate that a change from the current linear system to the RTG system could result in a reduction, per kilogram of tomatoes (the functional unit), in the range of 44.4-75.5% for the different impact categories analysed, and savings of up to 73.5% in energy requirements. These savings are associated with re-utilisation of packaging systems (55.4-85.2%), minimisation of transport requirements (7.6-15.6%) and reduction of the loss of product during transportation and retail stages (7.3-37%). CONCLUSIONS: The RTG may become a strategic factor in the design of low-carbon cities in Mediterranean areas. Short term implementation in the city of Barcelona could result in savings of 66.1 tonnes of CO2 eq. ha(-1) when considering the global warming potential, and of 71.03 t ha(-1) when considering that the transformation from woodland to agricultural land is avoided. PMID- 22674218 TI - Estimation of the amount of beta2-glycoprotein I adsorbed at the inner surface of fused silica capillaries after acidic, neutral and alkaline pretreatment. AB - Sample adsorption to the inner surface of fused silica capillaries is a common problem in CE when analyzing macromolecules and is harmful to the analysis. We previously utilized the pH hysteresis effect of fused silica to facilitate electrophoresis of the strongly adsorbing protein beta(2) gpI in plain-fused silica capillaries at neutral pH. In the present paper, the effect of different pretreatments of the capillary on the adsorption of the beta(2) -glycoprotein I has been investigated using electroosmosis markers, SDS mobilization, and imaging based on indirect immunofluorescence microscopy for direct visualization. The amount of beta(2) gpI adsorbed on the surface was probed using all these independent techniques after electrophoresis at neutral pH on capillaries pretreated with HCl, background electrolyte (BGE), and NaOH. BGE pretreatment was included as a positive control. We found that 80% or more of the starting material was adsorbed to the inner surface of the silica capillaries during electrophoresis after pretreatment with only BGE or with NaOH, but after acidic pretreatment the loss was consistently less than 20%. NaOH most efficiently removes adsorbed protein between runs. A theoretical calculation of the pH change of the BGE showed that electrolysis affects the pH more than the deprotonation of silanols during electrophoresis. We conclude that acidic pretreatment of fused silica capillaries diminishes adsorption of beta(2) gpI by decreasing charge dependent wall adsorption. PMID- 22674217 TI - The brain's response to an essential amino acid-deficient diet and the circuitous route to a better meal. AB - The essential (indispensable) amino acids (IAA) are neither synthesized nor stored in metazoans, yet they are the building blocks of protein. Survival depends on availability of these protein precursors, which must be obtained in the diet; it follows that food selection is critical for IAA homeostasis. If even one of the IAA is depleted, its tRNA becomes quickly deacylated and the levels of charged tRNA fall, leading to disruption of global protein synthesis. As they have priority in the diet, second only to energy, the missing IAA must be restored promptly or protein catabolism ensues. Animals detect and reject an IAA deficient meal in 20 min, but how? Here, we review the molecular basis for sensing IAA depletion and repletion in the brain's IAA chemosensor, the anterior piriform cortex (APC). As animals stop eating an IAA-deficient meal, they display foraging and altered choice behaviors, to improve their chances of encountering a better food. Within 2 h, sensory cues are associated with IAA depletion or repletion, leading to learned aversions and preferences that support better food selection. We show neural projections from the APC to appetitive and consummatory motor control centers, and to hedonic, motivational brain areas that reinforce these adaptive behaviors. PMID- 22674219 TI - NOS-like-mediated nitric oxide is involved in Pinus thunbergii response to the invasion of Bursaphelenchus xylophilus. AB - The content of NO and H(2)O(2) as well as the activities of nitric oxide synthase (NOS)-like and nitrate reductase (NR) were monitored in the needles of Pinus thunbergii infected by Bursaphelenchus xylophilus. The results showed that the content of NO increased significantly only 8 h after the invasion of B. xylophilus, while H(2)O(2) increased 12 h after invasion. NO donor SNP could promote and NO scavenger cPTIO could prevent the production of NO and H(2)O(2). The content of NO changed earlier than that of H(2)O(2). In addition, the symptoms appeared 9, 5 and 12 days, respectively, after the inoculation with B. xylophilus, SNP pre-treatment and cPTIO pre-treatment followed by B. xylophilus infection. After B. xylophilus infection, the content of NO in P. thunbergii changed fiercely more earlier than the appearance of external symptoms, which indicated that the content of NO was related with the appearance and the development of the symptoms. The treatment with L-NNA (NOS inhibitor) inhibited the content of NO significantly, whereas, Na(2)WO(4) (NR inhibitor) had no effect. The further analysis of NOS revealed that NO changed in consistent with cNOS activity. To sum up, NO, as the upstream signal molecule of H(2)O(2), was involved in the pine early response to the invasion of B. xylophilus and influenced the accumulation of the content of H(2)O(2). Moreover, NOS-like rather than NR was responsible for the endogenous NO generation, which was modulated by cNOS during the interaction between P. thunbergii and B. xylophilus. Key message NO is involved in early response of P. thunbergii to the invasion of B. xylophilus and NOS is the key enzyme responsible for NO generation in P. thunbergii. PMID- 22674220 TI - The quantitative Gleason score improves prostate cancer risk assessment. AB - BACKGROUND: In the current study, the authors propose the quantitative Gleason score (qGS), a modification of the current Gleason grading system for prostate cancer, based on the weighted average of Gleason patterns present in the pathology specimen. They hypothesize that the qGS can improve prostate cancer risk stratification and help prevent the overtreatment of patients with clinically indolent tumors. METHODS: The qGS was applied to patients in the University of California San Francisco urologic oncology database with tumors determined to have a GS of 7 on prostate biopsy or final pathology after radical prostatectomy (RP). Using multivariable logistic regression, Cox proportional hazards regression, receiver operating characteristic (ROC), and decision curve analyses, the ability of qGS to predict pathological GS and the risk of disease recurrence after RP was assessed. RESULTS: A total of 225 men were included in the analysis of biopsy specimens and 618 men were included in the assessment of RP specimens. Compared with traditional Gleason scoring, the qGS improved concordance between biopsy and pathological GS on decision curve and ROC analyses (area under the curve ROC curve, 0.79 vs 0.71). On regression analysis, the qGS of biopsy specimens was found to be significantly associated with pathological grade after RP (hazard ratio [HR], 1.78; 95% confidence interval [95% CI], 1.49 2.12) and the qGS of RP specimens was significantly associated with the risk of biochemical disease recurrence after RP (HR, 1.13; 95% CI, 1.04-1.24). CONCLUSIONS: The qGS, a simple modification of the current Gleason system, appears to improve the correlation between biopsy and pathological GS, as well as the prediction of biochemical disease recurrence after RP. This scoring system may allow more men to pursue active surveillance, thereby avoiding the morbidity of prostate cancer treatment modalities. PMID- 22674221 TI - The mesenchymal stem cell marker CD248 (endosialin) is a negative regulator of bone formation in mice. AB - OBJECTIVE: CD248 (tumor endothelial marker 1/endosialin) is found on stromal cells and is highly expressed during malignancy and inflammation. Studies have shown a reduction in inflammatory arthritis in CD248-knockout (CD248(-/-) ) mice. The aim of the present study was to investigate the functional effect of genetic deletion of CD248 on bone mass. METHODS: Western blotting, polymerase chain reaction, and immunofluorescence were used to investigate the expression of CD248 in humans and mice. Micro-computed tomography and the 3-point bending test were used to measure bone parameters and mechanical properties of the tibiae of 10 week-old wild-type (WT) or CD248(-/-) mice. Human and mouse primary osteoblasts were cultured in medium containing 10 mM beta-glycerophosphate and 50 MUg/ml ascorbic acid to induce mineralization, and then treated with platelet-derived growth factor BB (PDGF-BB). The mineral apposition rate in vivo was calculated by identifying newly formed bone via calcein labeling. RESULTS: Expression of CD248 was seen in human and mouse osteoblasts, but not osteoclasts. CD248(-/-) mouse tibiae had higher bone mass and superior mechanical properties (increased load required to cause fracture) compared to WT mice. Primary osteoblasts from CD248( /-) mice induced increased mineralization in vitro and produced increased bone over 7 days in vivo. There was no decrease in bone mineralization and no increase in proliferation of osteoblasts in response to stimulation with PDGF-BB, which could be attributed to a defect in PDGF signal transduction in the CD248(-/-) mice. CONCLUSION: There is an unmet clinical need to address rheumatoid arthritis associated bone loss. Genetic deletion of CD248 in mice results in high bone mass due to increased osteoblast-mediated bone formation, suggesting that targeting CD248 in rheumatoid arthritis may have the effect of increasing bone mass in addition to the previously reported effect of reducing inflammation. PMID- 22674222 TI - Hematologic malignancies: an opportunity to fill a gap in cancer surveillance. AB - BACKGROUND: Reporting of hematologic malignancies is an increasingly important focus for cancer surveillance. As trends in cancer care are shifting to the outpatient setting, hospital-based data collection methods used for cancer surveillance will result in under-reporting of these cancers. This study describes the testing and validation of an automated system for capturing and reporting cancers from community oncology providers. METHODS: The system was evaluated in 5 oncology practices in two states processing claims data for a 4- or 8-month interval. Resulting cancers were matched with the state registries. A random sample of nonmatched cases was reabstracted to measure the accuracy of the claims data for reporting of hematologic malignancies. RESULTS: The overall match rate for the 1,935 hematologic malignancies reported during the study period was 58.2 % (range, 37.4 % for CLL to 71.2 % for Hodgkin's Lymphoma). The overall accuracy rate for billing-reported hematologic malignancies was 95 %. Accuracy among cases that did not match with the cancer registry was 88 %. The estimated number of missed cases for the five participating practices ranged from 0.8 leukemia cases/oncologist/year to 3.4 CLL cases/oncologist/year. The estimated total number of missed cases in the five participating practices was 292 with an interquartile range of 263-323. CONCLUSION: As cancer diagnosis and treatment continue migration into ambulatory physician practice settings unreported hematopoietic cases will become increasingly problematic. Leveraging the standardized electronic billing data for automated reporting of cancer cases from physician practices may be an efficient method to reduce this gap in cancer surveillance reporting. PMID- 22674223 TI - Gastrectomy and risk of pancreatic cancer: systematic review and meta-analysis of observational studies. AB - PURPOSE: To investigate the association between gastrectomy and risk of pancreatic cancer (PaC). METHODS: We identified eligible studies in Medline and EMBASE up to 11 February 2012 and the reference lists of original studies and review articles on this topic. Summary relative risks with their 95 % confidence intervals were calculated with a random-effects model. Between-study heterogeneity was assessed using Cochran Q and I (2) statistics. RESULTS: Fifteen studies (11 case-control studies and 4 cohort studies) met eligibility criteria. The current data suggest that gastrectomy is associated with a 54 % excess risk of PaC (SRRs = 1.54; 95 % CI, 1.25-1.90; test for heterogeneity Q = 17.94, p < 0.001, I (2) = 22 %). There was no publication bias in the present meta-analysis. CONCLUSION: A significant increased risk of PaC exists in patients who have undergone gastrectomy, particularly those receiving Billroth II resection with a long postoperative interval. PMID- 22674224 TI - Variation in xenobiotic transport and metabolism genes, household chemical exposures, and risk of childhood acute lymphoblastic leukemia. AB - BACKGROUND: Recent studies suggest that environmental exposures to pesticides, tobacco, and other xenobiotic chemicals may increase risk of childhood acute lymphoblastic leukemia (ALL). We sought to evaluate the role of genes involved in xenobiotic transport and metabolism in childhood ALL risk, both alone and in conjunction with household chemical exposures previously found to be associated with childhood ALL risk. METHODS: We conducted a population-based epidemiologic study of 377 cases and 448 controls in California, utilizing a haplotype-based approach to evaluate 42 xenobiotic transport and metabolism genes in conjunction with data on self-reported household chemical exposures. RESULTS: We identified significant associations of childhood ALL risk with haplotypes of ABCB1, ARNT, CYP2C8, CYP1A2, CYP1B1, and IDH1. In addition, certain haplotypes showed significant joint effects with self-reported household chemical exposures on risk of childhood ALL. Specifically, elevated risks associated with use of paints in the home (ever) and indoor insecticides (pre-birth) were limited to subjects carrying specific haplotypes of CYP2C8 and ABCB1, respectively. CONCLUSIONS: Our results provide support for a role of xenobiotic transport and metabolism pathways in risk of childhood ALL and indicate that genes in these pathways may modulate the risk of disease associated with use of common household chemicals. Additional studies are needed to confirm these findings and localize specific causal variants. PMID- 22674225 TI - Racial differences in the relationship between tobacco, alcohol, and squamous cell carcinoma of the head and neck. AB - PURPOSE: Tobacco and alcohol use are well-known risk factors for squamous cell carcinoma of the head and neck (SCCHN), but there has been little examination of disparities in SCCHN and racial patterns of tobacco and alcohol use, especially for African-Americans. The Carolina Head and Neck Cancer Study, a population based case-control study, was utilized to determine whether relationships between tobacco and alcohol use and SCCHN differed by race. METHODS: Using a rapid case ascertainment system, cases were recruited from 46 contiguous counties in North Carolina from 2002 to 2006. Controls, selected from motor vehicle records, were frequency-matched to cases on age, sex, and race. This analysis was based on 989 white and 351 African-American cases and 1,114 white and 264 African-American controls. Analyses were performed using unconditional logistic regression, adjusting for age, sex, race, education, and fruit and vegetable consumption. RESULTS: The association between SCCHN and ever tobacco use among African Americans (odds ratio (OR), 9.68; 95 % confidence interval (CI), 4.70, 19.9) was much greater than that observed in whites (OR, 1.94; 95 % CI, 1.51, 2.50). Smaller differences were observed when examining ever alcohol use (African Americans: OR, 3.71; CI, 1.65, 8.30, and Whites: OR, 1.31: CI 0.96, 1.78). African-Americans consistently had greater effect measure estimates when examining common levels of duration and intensity metrics of tobacco and alcohol use, both independently and jointly. No racial differences in the effects of environmental (passive) tobacco smoke were observed. CONCLUSIONS: These findings suggest racial differences in SCCHN are not solely explained by differences in consumption patterns, and tobacco and alcohol may have greater impact in African Americans. PMID- 22674226 TI - Dilatation parameterization for two-dimensional modeling of nearly incompressible isotropic materials. AB - A new method to model the stress-strain relationship in two dimensions is proposed, which is particularly suited for analyzing nearly incompressible materials, such as soft tissue. In most cases of soft tissue modeling, plane strain is reported to approximate the deformation when an external compression is applied. However, it is subject to limitations when dealing with incompressible materials, e.g., when solving the inverse problem of elasticity. We propose a novel 2D model for the linear stress-strain relationship by describing the out-of plane strain as a linear combination of the two in-plane strains. As such, the model can be represented in 2D while being able to explain the three-dimensional deformation. We show that in simple cases where the applied force is dominantly in one direction, one can approximate the sum of the three principal strain components in a plane by a scalar multiplied by the out-of-plane strain. 3D finite-element simulations have been performed. The proposed model has been tested under different boundary conditions and material properties. The results show that the model parametrization is affected mostly by the boundary conditions, while being relatively independent of the underlying distribution of Young's modulus. An application to the inverse problem of elasticity is presented where a more accurate estimate is obtained using the proposed dilatation model compared to the plane-stress and plane-strain models. PMID- 22674227 TI - Thyroid cancer risk and dietary nitrate and nitrite intake in the Shanghai women's health study. AB - Nitrate and nitrite are precursors in the endogenous formation of N-nitroso compounds and nitrate can disrupt thyroid homeostasis by inhibiting iodide uptake. We evaluated nitrate and nitrite intake and risk of thyroid cancer in the Shanghai Women's Health Study that included 73,317 women, aged 40-70 years enrolled in 1996-2000. Dietary intake was assessed at baseline using a food frequency questionnaire. During approximately 11 years of follow-up, 164 incident thyroid cancer cases with complete dietary information were identified. We used Cox proportional hazards regression to estimate relative risks (RRs). We determined the nitrate and nitrite contents of foods using values from the published literature and focusing on regional values for Chinese foods. Nitrate intake was not associated with thyroid cancer risk [RR(Q4) = 0.93; 95% confidence interval (CI): 0.42-2.07; p for trend = 0.40]. Compared to the lowest quartile, women with the highest dietary nitrite intake had about a twofold risk of thyroid cancer (RR(Q4) = 2.05; 95%CI: 1.20-3.51), but there was not a monotonic trend with increasing intake (p for trend = 0.36). The trend with increasing nitrite intake from animal sources was significant (p for trend = 0.02) and was stronger for nitrite from processed meats (RR(Q4) = 1.96; 95%CI: 1.28-2.99; p for trend < 0.01). Although we did not observe an association for nitrate as hypothesized, our results suggest that women consuming higher levels of nitrite from animal sources, particularly from processed meat, may have an increased risk of thyroid cancer. PMID- 22674228 TI - Bis(tetrafluorophenyl)borane. AB - The reaction of the Grignard reagent (p-C(6)F(4)H)MgBr with Me(2)SnCl(2) afforded the p-C(6)F(4)H transfer reagent Me(2)Sn(p-C(6)F(4)H)(2) (1). Subsequent reaction of 1 with BCl(3) led to the chloroborane (p-C(6)F(4)H)(2)BCl (2), which was converted to the borane [(p-C(6)F(4)H)(2)BH](2) (3) by treatment with the hydride source Me(2)SiHCl. By reaction of tetrafluoropyridine with i-PrMgCl followed by the in situ reaction with Me(2)SnCl(2), the stannane Me(2)Sn(C(5)F(4)N)(2) (4) could be obtained. However, this did not react with BCl(3). The resulting products were characterized by elemental analyses and NMR spectroscopy. Single crystal X-ray diffraction experiments were performed for compounds 1, 2 and 4. The crystal structure of the literature known compound Me(2)Sn(C(6)F(5))(2) (5) was determined and compared with structures of 1 and 4. PMID- 22674229 TI - Does increased health care spending afford better health care outcomes? Evidence from Austrian health care expenditure since the implementation of DRGs. AB - AIMS: While it is commonly accepted that health care costs have been rising to unprecedented levels, the question remains whether the increased expenditure actually affords increased health outcomes. It was the objective of this study to search for associations between health care spending and health care outcome, after adjusting for potential confounding variables, using aggregate data collected since the introduction of diagnosis-related groups (DRG) into Austrian health care financing in 1997. METHODS: Two parameters of health care outcome, mortality and years of life lost (YLL), were regressed on direct and indirect measures of health care spending. We used ordinary least squares, Prais-Winsten, and 2-stage least squares regression in model building to account for autocorrelation and endogeneity. RESULTS: Our findings showed that health care spending was associated with mortality and YLL reduction. The strongest association among the independent variables was seen for spending for prevention. The strongest association for the dependent variables was seen for cardiovascular disease followed by injuries. Also, socio-economic status (SES) was shown to be an important confounder in all studied associations. Our data suggest that increases in health care spending produce significant increases in health. CONCLUSION: Health care spending should not be constrained, but instead an optimised resource allocation would afford an increase in health per expenditure. Emphasising spending in prevention and reduction of SES gradients would strengthen this association. PMID- 22674230 TI - Determination of binding affinity for chenodeoxycholate in equilibrium with sulfobutylether-beta-cyclodextrin. AB - A kinetic dialysis technique together with a radiolabeled chenodeoxycholate (CDC) was used to determine the existence of a relationship between the monomer concentration of CDC and the total CDC concentration in different CDC solutions containing 1 or 5 mM sulfobutylether (SBE)-beta-cyclodextrin. On the basis of the nature of the relationship and a binding model with binding constants of K1 and K2, the binding affinity for the solutions was quantified at the best curve fitting using a least-squares technique. The very high binding affinity of K1 and the very low (i.e., negligible) binding affinity of K2 indicate the formation of 1:1 inclusion complexes. In addition, the values of K1 and K2 were reasonably interpreted. Similar analysis showed that the formation of 1:2 inclusion complexes and the self-association of the SBE-beta-cyclodextrin molecules in the solutions are unlikely. The present study provides a basis for investigating the self-association, quantifying the binding affinity, and interpreting the quantified values. PMID- 22674231 TI - Analysis of energy saving lamps for use by photosensitive individuals. AB - Due to European legislation, the British government has begun the phase out of incandescent bulbs, to be replaced by energy-saving alternatives. The alternatives that are available on the market are Compact Fluorescent Lamps (CFL), Energy-Efficient Halogens (EEH) and Light Emitting Diodes (LED). Whilst previous research has shown that CFLs emit UVC, UVB and UVA, there is conflicting data available on whether double enveloped CFLs are a safer alternative to single enveloped CFLs for individuals suffering from photosensitivity. The emission spectra of 106 single enveloped CFLs and 65 double enveloped CFLs were measured. There were 17 different models of single enveloped CFLs, including lamps from 6 different manufacturers (ranging from 8-20 W) and 9 models of double enveloped CFLs from 6 different manufacturers (7-15 W). In addition, the emission spectra of 53 LEDs and 56 EEHs were also analysed. The LEDs consisted of 8 different models, from 3 manufacturers, spanning between 2.5 and 12 W. There were 11 models of EEH from 6 different manufacturers with wattages ranging from 28-70 W. In order to reduce sample bias, some bulbs were provided by the lighting industry federation and others were purchased randomly from local retailers. The results validate previous research in that considerable variation exists in the UV emitted from CFLs. This variation in UV levels is true, not only within different makes and models but also, surprisingly, within a box of 8 seemingly identical bulbs supplied by a single manufacturer. It was concluded that double enveloped CFLs do reduce the levels of UVC and UVB and therefore are a safer alternative for photosensitive individuals. However, as some double enveloped CFLs and EEHs do emit UVA at levels that provoke a reaction in the skin of UVA sensitive individuals, newly emerging LEDs that have minimal UV levels may provide a safer alternative. PMID- 22674232 TI - Information interventions for recovery following vehicle-related trauma to persons of working age: a systematic review of the literature. AB - OBJECTIVES: Given the burden associated with vehicle-related trauma, there is interest in time and cost effective methods of providing information to assist recovery. This systematic review aims to address the question: "Do targeted early information interventions improve outcomes following vehicle--related injuries for persons of working age?" DATA SOURCES: Ovid Medline, EMBASE, PsychINFO and Cochrane databases were searched for studies published between 1990-April 2011. DATA SELECTION: Included studies were randomized or pseudo--randomized controlled trials of information interventions delivered to working age persons following vehicle-related injuries. Two reviewers independently selected and appraised the studies. DATA SYNTHESIS: Sixteen publications (13 primary studies) met the inclusion criteria and were assessed for bias. Hetero-geneity in terms of the information interventions and measured outcomes was encountered. In 4 of the included studies, the intervention was positively associated with at least one outcome reported. Methodological issues limited the conclusions that could be drawn. CONCLUSION: Following vehicle-related trauma, people often experience difficulties in ongoing functioning. The current evidence neither supports nor fails to support the effectiveness of information interventions in promoting injury recovery. There is a need for larger more methodologically and conceptually rigorous randomized controlled trials that better consider the type and timing of the intervention. PMID- 22674233 TI - Evaluation of functional outcomes of physical rehabilitation and medical complications in spinal cord injury victims of the Sichuan earthquake. AB - OBJECTIVES: To characterize a spinal cord injury (SCI) population from the 2008 Sichuan earthquake in China; to evaluate functional outcomes of physical rehabilitation interventions; to assess potential determinants of rehabilitation effectiveness; and to assess medical complications and management outcomes. METHODS: A total of 51 earthquake victims with SCI were enrolled and underwent rehabilitation programming. Functional rehabilitation outcomes included ambulation ability, wheelchair mobility and activities of daily living (ADL) assessed with the Modified Barthel Index at the beginning and end of rehabilitation. Effectiveness of rehabilitation and the effect of other predictors were evaluated by mixed effects regression. Outcomes of medical complication management were determined by comparison of the incidence of respective complications at the beginning and end of rehabilitation. RESULTS: Ambulation, wheelchair mobility and ADL were significantly improved with rehabilitation programming. Both earlier rescue and earlier onset of rehabilitation were significant positive predictors of rehabilitation effectiveness, whereas delayed onset of rehabilitation combined with prolonged time to rescue resulted in a lesser positive effect. Medical complications were managed effectively in 63% (pressure ulcers) to 85% (deep vein thrombosis) of patients during rehabilitation. CONCLUSION: Earthquake victims with SCI may achieve significantly improved functional rehabilitation functional outcomes on a formal, institutional-based physical rehabilitation programme. PMID- 22674234 TI - Somatosensory evoked potentials of hand muscles in stroke and their modification by botulinum toxin: a preliminary study. AB - OBJECTIVE: To determine the effect of botulinum toxin A on spasticity and somatosensory evoked potentials of hand muscles in patients who have undergone cerebrovascular accident. DESIGN: Preliminary, prospective, before-after study design. PATIENTS: Six subjects prospectively followed after application of botulinum toxin A in the rehabilitation department of a university hospital. METHODS: All patients underwent botulinum toxin A injection to the upper extremity muscles in varying combinations and carried out a home-based exercise programme. Primary outcome measure was median somatosensory evoked potential of hand muscles (N20). Secondary outcome measures were: spasticity assessed clinically by Modified Ashworth Scales (MAS); functional ability analysis assessed by Physician's Rating Scale (PRS); and functional difficulties reported by patients or their care-givers by patient disability and care-giver burden rating scale (PD & CBRS). RESULTS: MAS, PRS and PD & CBRS improved with botulinum toxin A treatment. In the affected limb, N20 potentials were impaired compared with those in the unaffected side. With botulinum toxin A treatment, although improvement in overall N20-P25 amplitudes was significant, as a result of limited sample size, post hoc pair-wise comparisons with Bonferroni correction failed to yield any significant pairs. CONCLUSION: The improvement in the median somatosensory evoked potentials following botulinum toxin A treatment suggests that central somatosensory patterns in hemiplegia can be modified by peripheral inputs. PMID- 22674235 TI - Five-year mortality and related prognostic factors after inpatient stroke rehabilitation: a European multi-centre study. AB - OBJECTIVE: To determine 5-year mortality and its association with baseline characteristics and functional status 6 months post-stroke for patients who received inpatient rehabilitation. DESIGN: A prospective rehabilitation-based cohort study. SUBJECTS: A total of 532 consecutive stroke patients from 4 European rehabilitation centres. METHODS: Predictors were recorded on admission. Barthel Index was assessed at 6 months (BI6mths) and patients were followed for 5 years post-stroke. Survival probability was computed using Kaplan-Meier analysis and compared across 3 BI6mths-classes (0-60, 65-90, 95-100) (log-rank test). Significant independent predictors were determined using multivariate Cox regression analysis (hazard ratio (HR)). RESULTS: Five-year cumulative risk of death was 29.12% (95% confidence interval (CI): 22.86-35.38). Age (HR=1.06, 95% CI: 1.04-1.09), cognitive impairment (HR=1.77, 95% CI: 1.21-2.57), diabetes mellitus (HR=1.68, 95% CI: 1.16-2.41) and atrial fibrillation (HR=1.52, 95% CI: 1.08-2.14) were independent predictors of increased mortality. Hyperlipidaemia (HR=0.66, 95% CI: 0.46-0.94), and higher BI6mths (HR=0.98, 95% CI: 0.97-0.99) were independent predictors of decreased mortality. Five-year survival probability was 0.85 (95% CI: 0.80-0.89) for patients in BI6mths-class: 95-100, 0.72 (95% CI: 0.63-0.79) in BI6mths-class: 65-90 and 0.50 (95% CI: 0.40-0.60) in BI6mths-class: 0-60 (p<0.0001). CONCLUSION: Nearly one-third of rehabilitation patients died during the first 5 years following stroke. Functional status at 6 months was a powerful predictor of long-term mortality. Maximum functional independence at 6 months post-stroke should be promoted through medical interventions and rehabilitation. Future studies are recommended to evaluate the direct effect of rehabilitation on long-term survival. PMID- 22674236 TI - Sonography and physical findings in stroke patients with hemiplegic shoulders: a longitudinal study. AB - OBJECTIVE: To investigate the correlation between hemiplegic shoulder pain factors during the acute and chronic stages of stroke recovery. DESIGN: A prospective longitudinal study. SUBJECTS: Seventy-six stroke patients with hemiplegic shoulders. METHODS: Hemiplegic shoulder pain and clinical, physical, and sonography results were recorded at admission and during both acute (before discharge) and chronic stages (6 months after discharge). RESULTS: During the acute stage, hemiplegic shoulder pain correlated significantly with shoulder motor function level and range of motion limitations. During the chronic stage, hemiplegic shoulder pain correlated significantly with shoulder motor function level, range of motion limitations, spasticity and abnormal sonographic findings. Higher incidence (p=0.014) of hemiplegic shoulder pain and pain scores (p<0.01) were noted and abnormal sonographic findings of the biceps tendon long head (p=0.01) and subscapularis tendon (p=0.01) were higher during the chronic stage. Effusion, tenosynovitis or tendinopathy of the biceps tendon long head, and supraspinatus tendinopathy were notable during both stages. CONCLUSION: Hemiplegic shoulder pain was correlated with lower motor function level and shoulder range of motion limitation in both stages. Shoulder spasticity and abnormal sonographic findings were correlated with hemiplegic shoulder pain during the chronic stage. PMID- 22674237 TI - Spasticity management with botulinum toxin: development and evaluation of a tool for audit. AB - OBJECTIVE: To develop and evaluate tools for the audit of spasticity management with botulinum toxin. DESIGN: Audit tools to assess the organisation of services and process of care were developed with a consensus process. The tools were piloted across 8 services using a retrospective case note audit. Inter-rater reliability was assessed, using percentage agreement and kappa scores. Clinicians involved in the pilot were surveyed and qualitative feedback was analysed. RESULTS: Eight services (100%) completed service Organisation tools and 7 (88%) returned process of Care tools. One hundred sets of clinical records were audited, with 34 used to assess inter-rater reliability. Eleven items on the process of care tool demonstrated a good degree of inter-rater agreement, but 6 require further development. In the qualitative analysis clinicians stated that the tools captured indicators of quality, and that they would use them again. They recommended that patient satisfaction was included as a measure of quality. The audit has been used practically in the pilot services to provide an impetus for quality improvement. CONCLUSIONS: The majority of the audit questions showed a good level of reliability, and clinician feedback supports face validity but a larger scale evaluation is required. PMID- 22674238 TI - International Classification of Functioning, Disability and Health categories explored for self-rated participation in Swedish adolescents and adults with a mild intellectual disability. AB - OBJECTIVE: To explore internal consistency and correlations between perceived ability, performance and perceived importance in a preliminary selection of self reported items representing the activity/participation component of the International Classification of Functioning, Disability and Health (ICF). DESIGN: Structured interview study. SUBJECTS: Fifty-five Swedish adolescents and adults with a mild intellectual disability. METHODS: Questions about perceived ability, performance and perceived importance were asked on the basis of a 3-grade Likert scale regarding each of 68 items representing the 9 ICF domains of activity/participation. RESULTS: Internal consistency for perceived ability (Cronbach's alpha for all 68 items): 0.95 (values for each domain varied between 0.57 and 0.85), for performance: 0.86 (between 0.27 and 0.66), for perceived importance: 0.84 (between 0.27 and 0.68). Seventy-two percent of the items showed correlations >0.5 (mean=0.59) for performance vs perceived importance, 41% >0.5 (mean=0.47) for perceived ability vs performance and 12% >0.5 (mean=0.28) for perceived ability vs perceived importance. CONCLUSION: Measures of performance and perceived importance may have to be based primarily on their estimated clinical relevance for describing aspects of the ICF participation concept. With a clinimetric approach, parts of the studied items and domains may be used to investigate factors related to different patterns and levels of participation, and outcomes of rehabilitation. PMID- 22674239 TI - Relevance and completeness of the International Classification of Functioning, Disability and Health (ICF) comprehensive breast cancer core set: the patient perspective in an Australian community cohort. AB - OBJECTIVE: To examine the relevance and completeness of the International Classification of Functioning, Disability and Health (ICF) comprehensive core set for breast cancer using patient reported disability in an Australian cohort. METHOD: Cross-sectional community survey of 85 women following definitive treatment for primary breast cancer. Everyday living problems reported by participants (using open ended questionnaires) were linked with ICF categories using 'linkage' rules. Participants rated 'Activities and Participation' and 'Environmental factors' components of ICF checklist using World Health Organisation qualifiers (0-4). The impact of breast cancer on health areas corresponding to 90 ICF categories in these two components was assessed; and compared with ICF categories within the comprehensive breast cancer core set. RESULTS: Participants identified 16 of 22 categories from 'Activities and Participation' and 11 of 23 categories (barriers) from 'Environmental factors' included in the comprehensive Core Set for BC, as relevant (>= 10% of the participants). Median number of problems reported was 4 (IQR 1-9) and 1 (IQR 1-4) for 'Activities and Participation' and 'Environmental factors' categories', respectively. Thirteen additional relevant categories relating to mobility, major life areas, community civic life and societal attitudes currently not included in the breast cancer core set, were identified. CONCLUSION: The comprehensive breast cancer core set needs to incorporate issues important to survivors with breast cancer in post-acute settings, prior to its validation from a global perspective. PMID- 22674240 TI - An occupational, internet-based intervention to prevent chronicity in subacute lower back pain: a randomised controlled trial. AB - OBJECTIVE: To investigate whether an online occupational postural and exercise intervention reduced patients' overall risk status for chronicity in subacute non specific low back pain compared with conventional treatment, and to determine whether changes in risk of chronicity correlate with changes in specific outcomes (i.e. Functional Status and QoL) for low back pain. DESIGN: Prospective, single blinded randomized intervention study. SUBJECTS: University office workers with subacute non-specific low back pain (n=100) were randomized 1:1 to an intervention group, who received an online occupational postural and exercise intervention, and a control group. METHODS: Exercise and education materials used in the intervention were developed as an online resource, and included video demonstrations recorded in a laboratory. All sessions included exercises combining postural stability (for abdominal, lumbar, hip and thigh muscles) strengthening, flexibility, mobility, and stretching. Outcome measures included STarT Back Screening Tool (SBST), Roland Morris score, and European Quality of Life Questionnaire -5 dimensions - 3 levels. At 9 months, SBST was analysed and compared with the baseline and controls. RESULTS: Significant positive effects were found on mean scores recorded in the online occupational exercise intervention group for risk of chronicity (p<0.019). A correlation between functional disability, health-related quality of life and risk of chronicity of low back pain was observed. CONCLUSION: This study supports the potential utility of a real-time occupational internet-based intervention for preventing progression to chronicity of subacute non-specific low back pain among office workers. PMID- 22674241 TI - Association between rehabilitation timing and major complications of total knee arthroplatsy. AB - OBJECTIVE: To investigate the association between rehabilitation timing and the occurrence of post-total knee arthroplasty complications and related medical service utilization. METHODS: Data from Taiwan's National Health Insurance Research Database from 2003-2006 were used to perform a retrospective study on patients who received their initial total knee arthroplasty during 2004-2005 (a total of 21,143 subjects). All subjects were divided into 1 of 3 groups based on the timing of their rehabilitation after total knee arthroplasty, namely, the within 2 weeks group, the after 2 weeks group or the no-rehabilitation group. RESULTS: We found that patients in the no-rehabilitation group and the after 2 weeks group had higher incidences of prosthetic infection (odds ratio (OR) =1.29, p=0.0409; OR=1.66, p=0.0012) and deep venous thrombosis (OR=1.51, p=0.0099; OR=2.07; p=0.0007) than in the within-2-weeks group. In addition, compared with the within-2-weeks group, the after 2 weeks group had higher total medical expenses (exponentiated regression coefficient: Exp. (beta) =1.07, p=0.0211), and the no-rehabilitation group had lower total medical expenses (Exp. (beta) =0.01, p<0.0001). CONCLUSION: The results of this study indicated that, because the incidence rates of complications and medical service utilization among total knee arthroplasty patients in the within 2 weeks group were lower than in the after 2 weeks group, the timing of rehabilitation may be 1 factor affecting post-TKA complications and promoting high levels of medical service utilization. These findings could be useful for clinicians and health policymakers attempting to improve total knee arthroplasty services. PMID- 22674242 TI - Health services utilization in adult acquired major upper-limb amputees: a population-based survey. AB - OBJECTIVE: To increase knowledge of health services utilization and related factors in adult acquired major upper-limb amputees. DESIGN: Population-based cross-sectional study conducted in Norway. SUBJECTS: Two hundred and twenty four adult acquired major upper-limb amputees (57.4% response rate). Mean age was 53.7 years, 83.5% were men and mean post-amputation time was 24.0 years. METHODS: Data were collected by postal questionnaires. Amputation-related health services utilization, perceived benefit and unmet needs were reported and associations between these factors and background factors were estimated by multivariate logistic regression analyses. RESULTS: Reported health services utilization was relatively low. The reported benefit of utilized services was generally high. For several non-utilized services, considerable unmet needs for utilization were reported. Several background factors were significantly associated with different aspects of the services examined. A considerable discrepancy between reported pain and utilization of specified pain treatments was noted. CONCLUSION: The findings of this study suggest that several health services available to acquired major upper-limb amputees should be strengthened. Establishing routines to ensure access to optimal, individualized rehabilitation may prevent disability. We recommend additional, longitudinal studies to further assess the need for mental health care and pain treatment in acquired major upper-limb amputees. PMID- 22674243 TI - Triamcinolone acetonide vs procaine hydrochloride injection in the management of carpal tunnel syndrome: randomized placebo-controlled study. AB - OBJECTIVE: The aim of this trial was to compare the efficacy of triamcinolone acetonide and procaine HCl with that of placebo in the treatment of carpal tunnel syndrome. DESIGN: This prospective, randomized placebo-controlled trial included 57 patients (90 median nerves). Ninety median nerves were randomly assigned to 1 of 3 groups: group 1 was injected with 1 ml 0.09% saline, group 2 was injected with 40 mg triamcinolone acetonide, and group 3 was injected with 4 ml 1% procaine HCl. Clinical and electrophysiological evaluations were performed at study onset, and at 2 and 6 months post-treatment. RESULTS: At study onset no significant differences were observed between groups with respect to clinical and electrophysiological parameters. Clinical and electrophysiological evaluations was improved significantly in groups 2 and 3 at post-treatment (p<0.05). No significant changes were observed in group 1 (p>0.05). Moreover, groups 2 and 3 had better scores than group 1 at 2 and 6 months post-treatment(p<0.05). There was no difference between groups 2 and 3 in terms of change scores of any terms at post-treatment (p>0.05). CONCLUSION: Triamcinolone acetonide and procaine HCl injections are effective regarding short- and long-term outcomes compared with placebo injections, and procaine HCl injection was as effective as steroid injection. PMID- 22674244 TI - Relationship between finger flexion and extension force in healthy women and women with rheumatoid arthritis. AB - OBJECTIVE: Balance between flexor and extensor muscle activity is essential for optimal function. The purpose of this pilot study was to compare the relationship between maximum finger flexion force and maximum finger extension force in women with rheumatoid arthritis and healthy women. METHODS: Twenty healthy women (median age 61 years) and 20 women with rheumatoid arthritis (median age 59.5 years, median disease duration 16.5 years) were included in the study. Finger extension force was measured with an electronic device, EX-it, and finger flexion force using Grippit. The Grip Ability Test and the score from the patient reported outcome Disability Arm Shoulder and Hand were used to evaluate activity limitations. RESULTS: Patients with rheumatoid arthritis showed significantly decreased hand function compared with healthy controls. A correlation was found between extension force and flexion force in the healthy group (r = 0.65, p = 0.002),but not in the rheumatoid arthritis group (r = 0.25, p = 0.289). CONCLUSION: Impaired hand function appears to influence the relationship between maximum finger flexion and extension force. This study showed a difference in the relationship between maximum finger flexion and extension force in healthy controls and those with rheumatoid arthritis. PMID- 22674245 TI - The use of the Visual Analogue Scale (VAS) in rehabilitation outcomes. PMID- 22674246 TI - Physicochemical properties and emulsion stabilization of rice dreg glutelin conjugated with kappa-carrageenan through Maillard reaction. AB - BACKGROUND: Rice dreg is an underutilized source of cereal protein with good potential for application in the food industry. Glutelin represents about 850 g kg(-1) of total storage protein in rice dreg. The objective of this study was to characterize the physicochemical properties and emulsion stabilization of the Maillard type conjugate formed with rice dreg glutelin (RDG) and kappa carrageenan (1:2 weight ratio) dry-heated at 60 degrees C and 79% relative humidity for 24 h. RESULTS: Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Fourier transform-infrared analysis provided evidence on the formation of the Maillard type conjugation. Amino acid analysis suggested that the major locus during the Maillard reaction were lysine and arginine. Circular dichroism spectra showed decreasing amounts of alpha-helix and beta-strand in the products with increment in the amount of turns and random coil. Conjugation with kappa-carrageenan could significantly improve solubility of RDG (P < 0.05). Measurements of mean droplet size and creaming stability in oil-in-water emulsions showed that the conjugate was more effective at stabilizing emulsions at low pH or in the presence of high ionic strength. CONCLUSION: The Maillard reaction can be successfully used as a coupling method for RDG and kappa carrageenan to form the conjugate with improved solubility and emulsion stabilization. PMID- 22674247 TI - Clinical features of severe influenza A (H1N1) virus infection. AB - OBJECTIVE: To highlight the clinical presentations of influenza A (H1N1) infection, for early diagnosis and recognition by the pediatricians. METHODS: In this retrospective study, the medical records of inpatients with influenza A (H1N1) infection between November 1, 2009 and May 31, 2011 were reviewed. RESULTS: Eighty pediatric in-patients with median age 41.9 mo were studied. ARDS (11/80), pneumothorax (8/80), pleural effusion (7/80) and encephalopathy (7/80) were the most frequent complications. Six of 11 ARDS patients died;all of them were under 5 y. The median days of viral shedding was 11.4 d. Slight increase of Il-6, Il-10 and TNF-gamma were revealed in some cases. CONCLUSIONS: During late stage of pandemic wave, the majority of patients were young children. Children with severe Influenza A (H1N1) are prone to develop complications, and die from ARDS. If influenza-like illness is accompanied by neurologic signs, influenza A (H1N1) virus infection should be considered. The viral shedding in children is longer than in adults. PMID- 22674248 TI - Norrie disease: first mutation report and prenatal diagnosis in an Indian family. AB - Norrie Disease (ND) is a rare X-linked recessive disorder characterised by congenital blindness due to severe retinal dysgenesis. Hearing loss and intellectual disability is present in 30-50 % cases. ND is caused by mutations in the NDP gene, located at Xp11.3. The authors describe mutation analysis of a proband with ND and subsequently prenatal diagnosis. Sequence analysis of the NDP gene revealed a hemizygous missense mutation arginine to serine in codon 41 (p.Arg41Ser) in the affected child. Mother was carrier for the mutation. In a subsequent di-chorionic di-amniotic pregnancy, the authors performed prenatal diagnosis by mutation analysis on chorionic villi sample at 11 wk of gestation. The fetuses were unaffected. This is a first mutation report and prenatal diagnosis of a familial case of Norrie disease from India. The importance of genetic testing of Norrie disease for confirmation, carrier testing, prenatal diagnosis and genetic counseling is emphasized. PMID- 22674249 TI - Congenital central hypoventilation syndrome with PHOX2B gene mutation. AB - A term baby developed hypoventilation on day 1 of life requiring mechanical ventilation and had subsequent difficulty in weaning. Diagnostic workup for pulmonary, cardiac, metabolic, sepsis and structural CNS diseases were negative. In view of persistent hypoventilation despite raised pCO(2) levels in absence of any sedation, the diagnosis of Idiopathic. Congenital Central Hypoventilation Syndrome (CCHS) was considered. The baby was tested for Paired-like Homeobox 2B (PHOX2B) gene mutation and was found to have expanded alleles containing 10 polyalanine repeats producing genotype of 20/30 on chromosome 4p12 (The normal being 20/20). This is the first report of a neonate from India with genetically confirmed CCHS. PMID- 22674250 TI - Superior mediastinal syndrome : a rare presenting feature of acute myeloid leukemia. AB - Superior mediastinal syndrome (SMS) is an uncommon manifestation of malignant neoplastic disease in children. The commonest neoplastic cause of SMS is Non Hodgkin lymphoma. Acute myeloid leukemia (AML) as a cause of SMS is extremely uncommon in childhood. The authors hereby report a case of a child with AML who presented with SMS at their hospital. This report also highlights the importance of flowcytometry as a diagnostic modality in hematological malignancies. PMID- 22674251 TI - Electric fields caused by blood flow modulate vascular endothelial electrophysiology and nitric oxide production. AB - Endothelial cells are exposed to a ubiquitous, yet unexamined electrical force caused by blood flow: the electrokinetic vascular streaming potential (EVSP). In this study, the hypothesis that extremely low frequency (ELF) electric fields parameterized by the EVSP have significant biological effects on endothelial cell properties was studied by measuring membrane potential and nitric oxide production under ELF stimulation between 0 and 2 Hz and 0-6.67 V/m. Using membrane potential and nitric oxide sensitive fluorescent dyes, bovine aortic endothelial cells (BAECs) in culture were studied in the presence and absence of EVSP-modeled electric fields. The transmembrane potential of BAECs was shown to depolarize between 1 and 7 mV with a strong dependency on both the magnitude and frequency of the isolated ELF field. The findings also support a field interaction with a frequency-dependent tuning curve. The ELF field complexly modulates the nitric oxide response to adenosine triphosphate stimulation with potentiation seen with up to a sevenfold increase. This potentiation was also frequency and magnitude dependent. An early logarithmic phase of NO production is enhanced in a field strength-dependent manner, but the ELF field does not modify a later exponential phase. This study shows that using electric fields on the order of those generated by blood flow influences the essential biology of endothelial cells. The inclusion of ELF electric fields in the paradigm of vascular biology may create novel opportunities for advancing both the understanding and therapies for treatment of vascular diseases. PMID- 22674252 TI - Updating of an occluded moving target for interceptive saccades. PMID- 22674253 TI - The amygdala central nucleus: a new region implicated in habit learning. PMID- 22674254 TI - Clonal neural stem cells from human embryonic stem cell colonies. AB - Clonal cell culture is crucial for experimental protocols that require growth or selection of pure populations of cells. High-density derivation of neural progenitors from human embryonic stem cells (hESCs) can lead to incomplete differentiation, and transplantation of resulting heterogeneous cell mixtures can cause proliferation of tumorigenic clusters in vivo. We have identified the neural precursor that resides among normal hESC colonies as a TRA-1-60(-)/SSEA4( )/SOX1(+) cell and developed a method that allows for the clonal expansion of these FACS-selected progenitors to neural stem cells (NSCs) in serum-free conditions. Single TRA-1-60(-)/SSEA4(-)/SOX1(+) cells grown in serum-free media give rise to multipotent NSCs with an efficiency of 0.7%. The fate of the TRA-1 60(-)/SSEA4(-)/SOX1(+) neural precursor becomes specified in maintenance conditions by inhibition of BMP signaling. This clonal culture method can be scaled up to produce NSCs for differentiation and use in cell therapies. PMID- 22674255 TI - GABAergic synaptic transmission triggers action potentials in thalamic reticular nucleus neurons. AB - GABAergic neurons in the thalamic reticular nucleus (TRN) form powerful inhibitory connections with several dorsal thalamic nuclei, thereby controlling attention, sensory processing, and synchronous oscillations in the thalamocortical system. TRN neurons are interconnected by a network of GABAergic synapses, but their properties and their role in shaping TRN neuronal activity are not well understood. Using recording techniques aimed to minimize changes in the intracellular milieu, we show that synaptic GABA(A) receptor activation triggers postsynaptic depolarizations in mouse TRN neurons. Immunohistochemical data indicate that TRN neurons express very low levels of the Cl(-) transporter KCC2. In agreement, perforated-patch recordings show that intracellular Cl(-) levels are high in TRN neurons, resulting in a Cl(-) reversal potential (E(Cl)) significantly depolarized from rest. Additionally, we find that GABA(A) receptor evoked depolarizations are amplified by the activation of postsynaptic T-type Ca(2+) channels, leading to dendritic Ca(2+) increases and the generation of burst firing in TRN neurons. In turn, GABA-evoked burst firing results in delayed and long-lasting feedforward inhibition in thalamic relay cells. Our results show that GABA-evoked depolarizations can interact with T-type Ca(2+) channels to powerfully control spike generation in TRN neurons. PMID- 22674256 TI - GSK3 temporally regulates neurogenin 2 proneural activity in the neocortex. AB - The neocortex is comprised of six neuronal layers that are generated in a defined temporal sequence. While extrinsic and intrinsic cues are known to regulate the sequential production of neocortical neurons, how these factors interact and function in a coordinated manner is poorly understood. The proneural gene Neurog2 is expressed in progenitors throughout corticogenesis, but is only required to specify early-born, deep-layer neuronal identities. Here, we examined how neuronal differentiation in general and Neurog2 function in particular are temporally controlled during murine neocortical development. We found that Neurog2 proneural activity declines in late corticogenesis, correlating with its phosphorylation by GSK3 kinase. Accordingly, GSK3 activity, which is negatively regulated by canonical Wnt signaling, increases over developmental time, while Wnt signaling correspondingly decreases. When ectopically activated, GSK3 inhibits Neurog2-mediated transcription in cultured cells and Neurog2 proneural activities in vivo. Conversely, a reduction in GSK3 activity promotes the precocious differentiation of later stage cortical progenitors without influencing laminar fate specification. Mechanistically, we show that GSK3 suppresses Neurog2 activity by influencing its choice of dimerization partner, promoting heterodimeric interactions with E47 (Tcfe2a), as opposed to Neurog2 Neurog2 homodimer formation, which occurs when GSK3 activity levels are low. At the functional level, Neurog2-E47 heterodimers have a reduced ability to transactivate neuronal differentiation genes compared with Neurog2-Neurog2 homodimers, both in vitro and in vivo. We thus conclude that the temporal regulation of Neurog2-E47 heterodimerization by GSK3 is a central component of the neuronal differentiation "clock" that coordinates the timing and tempo of neocortical neurogenesis in mouse. PMID- 22674257 TI - STAT3-iNOS Signaling Mediates EGFRvIII-Induced Glial Proliferation and Transformation. AB - Malignant gliomas, including glioblastoma multiforme, constitute the most common and aggressive primary brain tumors in adults. The transcription factor signal transducer and activator of transcription 3 (STAT3) plays an essential role in glioblastoma pathogenesis downstream of the major oncogenic protein epidermal growth factor receptor variant III (EGFRvIII). However, the critical gene targets of STAT3 that mediate EGFRvIII-induced glial transformation have remained unknown. Here, we identify inducible nitric oxide synthase (iNOS) as a novel target gene of STAT3 in EGFRvIII-expressing mouse astrocytes. Endogenous STAT3 occupies the endogenous iNOS promoter and stimulates iNOS transcription in EGFRvIII-expressing astrocytes. STAT3 does not appear to control iNOS transcription in astrocytes deficient in the major glioblastoma tumor suppressor protein phosphatase and tensin homolog (PTEN), suggesting that STAT3 regulates iNOS transcription specifically in EGFRvIII-expressing astrocytes. Importantly, inhibition of iNOS by distinct approaches, including knockdown by RNA interference, reduces cell population growth and invasiveness of EGFRvIII expressing astrocytes. In addition, upon iNOS knockdown or administration of a small-molecule inhibitor of iNOS, EGFRvIII-expressing astrocytes form smaller tumors in vivo. These findings suggest that inhibition of iNOS may have potential therapeutic value for EGFRvIII-activated brain tumors. PMID- 22674258 TI - Neuronal classification and marker gene identification via single-cell expression profiling of brainstem vestibular neurons subserving cerebellar learning. AB - Identification of marker genes expressed in specific cell types is essential for the genetic dissection of neural circuits. Here we report a new strategy for classifying heterogeneous populations of neurons into functionally distinct types and for identifying associated marker genes. Quantitative single-cell expression profiling of genes related to neurotransmitters and ion channels enables functional classification of neurons; transcript profiles for marker gene candidates identify molecular handles for manipulating each cell type. We apply this strategy to the mouse medial vestibular nucleus (MVN), which comprises several types of neurons subserving cerebellar-dependent learning in the vestibulo-ocular reflex. Ion channel gene expression differed both qualitatively and quantitatively across cell types and could distinguish subtle differences in intrinsic electrophysiology. Single-cell transcript profiling of MVN neurons established six functionally distinct cell types and associated marker genes. This strategy is applicable throughout the nervous system and could facilitate the use of molecular genetic tools to examine the behavioral roles of distinct neuronal populations. PMID- 22674260 TI - A metaplasticity-like mechanism supports the selection of fear memories: role of protein kinase a in the amygdala. AB - How the brain determines which memories are selected for long-term storage is critical for a full understanding of memory. One possibility is that memories are selected based on the history of activity and current state of neurons within a given memory circuit. Many in vitro studies have demonstrated metaplasticity-like effects whereby prior neuronal activity can affect the ability of cells to express synaptic plasticity in the future; however, the significance of these findings to memory is less clear. Here we show in rats that a single pairing of a light with shock, insufficient to support either short- or long-term fear memory, primes future learning such that another trial delivered within a circumscribed time window lasting from ~60 min to 3 d results in the formation of a long lasting and robust fear memory. Two adequately spaced training trials support long-term fear memory only if the two trials are signaled by the same cue. Furthermore, although a single training trial does not support formation of an observable fear memory, it does result in the phosphorylation of several targets of protein kinase A (PKA) in the amygdala. Accordingly, blocking PKA signaling in the amygdala before the first training trial completely prevents the ability of that trial to facilitate the formation of long-term fear memory when a second trial is delivered 24 h later. These findings may provide insight into how memories are selected for long-term storage. PMID- 22674259 TI - Engrailed is required in maturing serotonin neurons to regulate the cytoarchitecture and survival of the dorsal raphe nucleus. AB - Analysis of constitutive Engrailed (En) null mice previously implicated the two En homeobox paralogs in the development of serotonin (5-HT) neurons. An unresolved question is whether En plays intrinsic roles in these neurons. Here, we show that En1 and En2 are expressed in maturing 5-HT neurons that will form the dorsal raphe nucleus (DRN) and part of the median raphe nucleus. Although En1 expression in 5-HT neurons persists postnatally, En2 expression is extinguished by embryonic day 17.5. To investigate intrinsic serotonergic functions for En1/2, we generated compound conditional En mutants with floxed alleles and a cre recombinase line that becomes active in postmitotic fetal 5-HT neurons. We present evidence in support of a requirement for En1/2 in the maturation of DRN cytoarchitecture. The disruption of DRN cytoarchitecture appears to result from a defect in secondary migration of serotonergic cell bodies toward the midline rather than disruption of their primary ventral migration away from the ventricular zone. Furthermore, En1/2 are required for perinatal maintenance of serotonergic identity and postnatal forebrain 5-HT levels. Increased numbers of caspase-3-expressing cells and loss of significant numbers of 5-HT neuron cell bodies, indicative of apoptosis, occurred after loss of serotonergic identity. Analysis of an allelic series of conditional mutants showed that En1 is the predominant functional En paralog in maturing 5-HT neurons, although a small contribution from En2 was reproducibly detected. Together, our findings reveal complex intrinsic functions for En in maturing 5-HT neurons, hence necessitating a reinterpretation of their roles in 5-HT system development. PMID- 22674261 TI - Neurotoxicity and memory deficits induced by soluble low-molecular-weight amyloid beta1-42 oligomers are revealed in vivo by using a novel animal model. AB - Neuronal and synaptic degeneration are the best pathological correlates for memory decline in Alzheimer's disease (AD). Although the accumulation of soluble low-molecular-weight amyloid-beta (Abeta) oligomers has been suggested to trigger neurodegeneration in AD, animal models overexpressing or infused with Abeta lack neuronal loss at the onset of memory deficits. Using a novel in vivo approach, we found that repeated hippocampal injections of small soluble Abeta(1-42) oligomers in awake, freely moving mice were able to induce marked neuronal loss, tau hyperphosphorylation, and deficits in hippocampus-dependent memory. The neurotoxicity of small Abeta(1-42) species was observed in vivo as well as in vitro in association with increased caspase-3 activity and reduced levels of the NMDA receptor subunit NR2B. We found that the sequestering agent transthyretin is able to bind the toxic Abeta(1-42) species and attenuated the loss of neurons and memory deficits. Our novel mouse model provides evidence that small, soluble Abeta(1-42) oligomers are able to induce extensive neuronal loss in vivo and initiate a cascade of events that mimic the key neuropathological hallmarks of AD. PMID- 22674262 TI - Emergence of coordinated plasticity in the cochlear nucleus and cerebellum. AB - Synapses formed by one cell type onto another cell type tend to show characteristic short-term plasticity, which varies from facilitating to depressing depending on the particular system. Within a population of synapses, plasticity can also be variable, and it is unknown how this plasticity is determined on a cell-by-cell level. We have investigated this in the mouse cochlear nucleus, where auditory nerve (AN) fibers contact bushy cells (BCs) at synapses called "endbulbs of Held." Synapses formed by different AN fibers onto one BC had plasticity that was more similar than would be expected at random. Experiments using MK-801 indicated that this resulted in part from similarity in the presynaptic probability of release. The similarity was not present in immature synapses but emerged after the onset of hearing. In addition, the phenomenon occurred at excitatory synapses in the cerebellum. This indicates that postsynaptic cells coordinate the plasticity of their inputs, which suggests that plasticity is of fundamental importance to synaptic function. PMID- 22674263 TI - State-dependent spike and local field synchronization between motor cortex and substantia nigra in hemiparkinsonian rats. AB - Excessive beta frequency oscillatory and synchronized activity has been reported in the basal ganglia of parkinsonian patients and animal models of the disease. To gain insight into processes underlying this activity, this study explores relationships between oscillatory activity in motor cortex and basal ganglia output in behaving rats after dopamine cell lesion. During inattentive rest, 7 d after lesion, increases in motor cortex-substantia nigra pars reticulata (SNpr) coherence emerged in the 8-25 Hz range, with significant increases in local field potential (LFP) power in SNpr but not motor cortex. In contrast, during treadmill walking, marked increases in both motor cortex and SNpr LFP power, as well as coherence, emerged in the 25-40 Hz band with a peak frequency at 30-35 Hz. Spike triggered waveform averages showed that 77% of SNpr neurons, 77% of putative cortical interneurons, and 44% of putative pyramidal neurons were significantly phase-locked to the increased cortical LFP activity in the 25-40 Hz range. Although the mean lag between cortical and SNpr LFPs fluctuated around zero, SNpr neurons phase-locked to cortical LFP oscillations fired, on average, 17 ms after synchronized spiking in motor cortex. High coherence between LFP oscillations in cortex and SNpr supports the view that cortical activity facilitates entrainment and synchronization of activity in basal ganglia after loss of dopamine. However, the dramatic increases in cortical power and relative timing of phase-locked spiking in these areas suggest that additional processes help shape the frequency specific tuning of the basal ganglia-thalamocortical network during ongoing motor activity. PMID- 22674264 TI - Color blobs in cortical areas V1 and V2 of the new world monkey Callithrix jacchus, revealed by non-differential optical imaging. AB - Color vision is reserved to only few mammals, such as Old World monkeys and humans. Most Old World monkeys are trichromats. Among them, macaques were shown to exhibit functional domains of color-selectivity, in areas V1 and V2 of the visual cortex. Such color domains have not yet been shown in New World monkeys. In marmosets a sex-linked dichotomy results in dichromatic and trichromatic genotypes, rendering most male marmosets color-blind. Here we used trichromatic female marmosets to examine the intrinsic signal response in V1 and V2 to chromatic and achromatic stimuli, using optical imaging. To activate the subsystems individually, we used spatially homogeneous isoluminant color opponent (red/green, blue/yellow) and hue versus achromatic flicker (red/gray, green/gray, blue/gray, yellow/gray), as well as achromatic luminance flicker. In contrast to previous optical imaging studies in marmosets, we find clearly segregated color domains, similar to those seen in macaques. Red/green and red/gray flicker were found to be the appropriate stimulus for revealing color domains in single condition maps. Blue/gray and blue/yellow flicker stimuli resulted in faint patch patterns. A recently described multimodal vessel mapping approach allowed for an accurate alignment of the functional and anatomical datasets. Color domains were tightly colocalized with cytochrome oxidase blobs in V1 and with thin stripes in V2. Thus, our findings are in accord with 2-Deoxy-D-glucose studies performed in V1 of macaques and studies on color representation in V2. Our results suggest a similar organization of early cortical color processing in trichromats of both Old World and New World monkeys. PMID- 22674265 TI - Irregular Breathing in Mice following Genetic Ablation of V2a Neurons. AB - Neural networks called central pattern generators (CPGs) generate repetitive motor behaviors such as locomotion and breathing. Glutamatergic neurons are required for the generation and inhibitory neurons for the patterning of the motor activity associated with repetitive motor behaviors. In the mouse, glutamatergic V2a neurons coordinate the activity of left and right leg CPGs in the spinal cord enabling mice to generate an alternating gait. Here, we investigate the role of V2a neurons in the neural control of breathing, an essential repetitive motor behavior. We find that, following the ablation of V2a neurons, newborn mice breathe at a lower frequency. Recordings of respiratory activity in brainstem-spinal cord and respiratory slice preparations demonstrate that mice lacking V2a neurons are deficient in central respiratory rhythm generation. The absence of V2a neurons in the respiratory slice preparation can be compensated for by bath application of neurochemicals known to accelerate the breathing rhythm. In this slice preparation, V2a neurons exhibit a tonic firing pattern. The existence of direct connections between V2a neurons in the medial reticular formation and neurons of the pre-Botzinger complex indicates that V2a neurons play a direct role in the function of the respiratory CPG in newborn mice. Thus, neurons of the embryonic V2a lineage appear to have been recruited to neural networks that control breathing and locomotion, two prominent CPG-driven, repetitive motor behaviors. PMID- 22674266 TI - Activity regulates functional connectivity from the vomeronasal organ to the accessory olfactory bulb. AB - The mammalian accessory olfactory system is specialized for the detection of chemicals that identify kin and conspecifics. Vomeronasal sensory neurons (VSNs) residing in the vomeronasal organ project axons to the accessory olfactory bulb (AOB), where they form synapses with principal neurons known as mitral cells. The organization of this projection is quite precise and is believed to be essential for appropriate function of this system. However, how this precise connectivity is established is unknown. We show here that in mice the vomeronasal duct is open at birth, allowing external chemical stimuli access to sensory neurons, and that these sensory neurons are capable of releasing neurotransmitter to downstream neurons as early as the first postnatal day (P). Using major histocompatibility complex class I peptides to activate a selective subset of VSNs during the first few postnatal days of development, we show that increased activity results in exuberant VSN axonal projections and a delay in axonal coalescence into well defined glomeruli in the AOB. Finally, we show that mitral cell dendritic refinement occurs just after the coalescence of presynaptic axons. Such a mechanism may allow the formation of precise connectivity with specific glomeruli that receive input from sensory neurons expressing the same receptor type. PMID- 22674267 TI - Structural variations in prefrontal cortex mediate the relationship between early childhood stress and spatial working memory. AB - A large corpus of research indicates that exposure to stress impairs cognitive abilities, specifically executive functioning dependent on the prefrontal cortex (PFC). We collected structural MRI scans (n = 61), well-validated assessments of executive functioning, and detailed interviews assessing stress exposure in humans to examine whether cumulative life stress affected brain morphometry and one type of executive functioning, spatial working memory, during adolescence-a critical time of brain development and reorganization. Analysis of variations in brain structure revealed that cumulative life stress and spatial working memory were related to smaller volumes in the PFC, specifically prefrontal gray and white matter between the anterior cingulate and the frontal poles. Mediation analyses revealed that individual differences in prefrontal volumes accounted for the association between cumulative life stress and spatial working memory. These results suggest that structural changes in the PFC may serve as a mediating mechanism through which greater cumulative life stress engenders decrements in cognitive functioning. PMID- 22674268 TI - Self-renewal and differentiation of reactive astrocyte-derived neural stem/progenitor cells isolated from the cortical peri-infarct area after stroke. AB - In response to stroke, subpopulations of cortical reactive astrocytes proliferate and express proteins commonly associated with neural stem/progenitor cells such as glial fibrillary acidic protein (GFAP) and Nestin. To examine the stem cell related properties of cortical reactive astrocytes after injury, we generated GFAP-CreER(TM);tdRFP mice to permanently label reactive astrocytes. We isolated cells from the cortical peri-infarct area 3 d after stroke, and cultured them in neural stem cell medium containing epidermal growth factor and basic fibroblast growth factor. We observed tdRFP-positive neural spheres in culture, suggestive of tdRFP-positive reactive astrocyte-derived neural stem/progenitor cells (Rad NSCs). Cultured Rad-NSCs self-renewed and differentiated into neurons, astrocytes, and oligodendrocytes. Pharmacological inhibition and conditional knock-out mouse studies showed that Presenilin 1 and Notch 1 controlled neural sphere formation by Rad-NSCs after stroke. To examine the self-renewal and differentiation potential of Rad-NSCs in vivo, Rad-NSCs were transplanted into embryonic, neonatal, and adult mouse brains. Transplanted Rad-NSCs were observed to persist in the subventricular zone and secondary Rad-NSCs were isolated from the host brain 28 d after transplantation. In contrast with neurogenic postnatal day 4 NSCs and adult NSCs from the subventricular zone, transplanted Rad-NSCs differentiated into astrocytes and oligodendrocytes, but not neurons, demonstrating that Rad-NSCs had restricted differentiation in vivo. Our results indicate that Rad-NSCs are unlikely to be suitable for neuronal replacement in the absence of genetic or epigenetic modification. PMID- 22674269 TI - Acetylcholine receptor gating in a zebrafish model for slow-channel syndrome. AB - Slow-channel syndrome (SCS) is an autosomal-dominant disease resulting from mutations in muscle acetylcholine (ACh) receptor subunits. The associated fatigue and muscle degeneration are proposed to result from prolonged synaptic responses that overload intracellular calcium. Single-channel studies on reconstituted receptors bearing human mutations indicate that the prolonged responses result from an increase in receptor open duration and, in some cases, increased sensitivity to ACh. We show that both of these aberrant receptor properties are recapitulated in heterozygotic zebrafish bearing an L258P mutation in the alpha subunit, thus affording the unique opportunity to compare the single-channel properties of mutant receptors to the synaptic currents in vivo. Whole-cell recordings revealed synaptic currents that decayed along a multiexponential time course, reflecting receptors containing mixtures of wild-type and mutant alpha subunits. Treatment with quinidine, an open-channel blocker used to treat the human disorder, restored fast synaptic current kinetics and the ability to swim. Quinidine block also revealed that mutant receptors generate a large steady-state current in the absence of ACh. The spontaneous openings reflected a destabilization of the closed state, leading to an apparent increase in the sensitivity of these receptors to ACh. The effective block by quinidine on synaptic currents as well as nonliganded openings points to dual sources for the calcium-dependent myopathy in certain forms of SCS. PMID- 22674270 TI - Retronasal odor representations in the dorsal olfactory bulb of rats. AB - Animals perceive their olfactory environment not only from odors originating in the external world (orthonasal route) but also from odors released in the oral cavity while eating food (retronasal route). Retronasal olfaction is crucial for the perception of food flavor in humans. However, little is known about the retronasal stimulus coding in the brain. The most basic questions are if and how route affects the odor representations at the level of the olfactory bulb (OB), where odor quality codes originate. We used optical calcium imaging of presynaptic dorsal OB responses to odorants in anesthetized rats to ask whether the rat OB could be activated retronasally, and how these responses compare to orthonasal responses under similar conditions. We further investigated the effects of specific odorant properties on orthonasal versus retronasal response patterns. We found that at a physiologically relevant flow rate, retronasal odorants can effectively reach the olfactory receptor neurons, eliciting glomerular response patterns that grossly overlap with those of orthonasal responses, but differ from the orthonasal patterns in the response amplitude and temporal dynamics. Interestingly, such differences correlated well with specific odorant properties. Less volatile odorants yielded relatively smaller responses retronasally, but volatility did not affect relative temporal profiles. More polar odorants responded with relatively longer onset latency and time to peak retronasally, but polarity did not affect relative response magnitudes. These data provide insight into the early stages of retronasal stimulus coding and establish relationships between orthonasal and retronasal odor representations in the rat OB. PMID- 22674271 TI - PLD1 Negatively Regulates Dendritic Branching. AB - Neurons have characteristic dendritic arborization patterns that contribute to information processing. One essential component of dendritic arborization is the formation of a specific number of branches. Although intracellular pathways promoting dendritic growth and branching are being elucidated, the mechanisms that negatively regulate the branching of dendrites remain enigmatic. In this study, using gain-of-function and loss-of-function studies, we show that phospholipase D1 (PLD1) acts as a negative regulator of dendritic branching in cultured hippocampal neurons from embryonic day 18 rat embryos. Overexpression of wild-type PLD1 (WT-PLD1) decreases the complexity of dendrites, whereas knockdown or inhibition of PLD1 increases dendritic branching. We further demonstrated that PLD1 acts downstream of RhoA, one of the small Rho GTPases, to suppress dendritic branching. The restriction of dendritic branching by constitutively active RhoA (V14-RhoA) can be partially rescued by knockdown of PLD1. Moreover, the inhibition of dendritic branching by V14-RhoA and WT-PLD1 can be partially ameliorated by reducing the level of phosphatidic acid (PA), which is the enzymatic product of PLD1. Together, these results suggest that RhoA-PLD1-PA may represent a novel signaling pathway in the restriction of dendritic branching and may thus provide insight into the mechanisms of dendritic morphogenesis. PMID- 22674272 TI - Parallel mitral and tufted cell pathways route distinct odor information to different targets in the olfactory cortex. AB - Odor signals are conveyed from the olfactory bulb to the olfactory cortex (OC) by mitral cells (MCs) and tufted cells (TCs). However, whether and how the two types of projection neuron differ in function and axonal connectivity is still poorly understood. Odor responses and axonal projection patterns were compared between MCs and TCs in mice by visualizing axons of electrophysiologically identified single neurons. TCs demonstrated shorter onset latency for reliable responses than MCs. The shorter latency response of TCs was maintained in a wide range of odor concentrations, whereas MCs responded only to strong signals. Furthermore, individual TCs projected densely to focal targets only in anterior areas of the OC, whereas individual MCs dispersedly projected to all OC areas. Surprisingly, in anterior OC areas, the two cell types projected to segregated subareas. These results suggest that MCs and TCs transmit temporally distinct odor information to different OC targets. PMID- 22674273 TI - Gray matter density of auditory association cortex relates to knowledge of sound concepts in primary progressive aphasia. AB - Long-term memory integrates the multimodal information acquired through perception into unified concepts, supporting object recognition, thought, and language. While some theories of human cognition have considered concepts to be abstract symbols, recent functional neuroimaging evidence has supported an alternative theory: that concepts are multimodal representations associated with the sensory and motor systems through which they are acquired. However, few studies have examined the effects of cortical lesions on the sensory and motor associations of concepts. We tested the hypothesis that individuals with disease in auditory association cortex would have difficulty processing concepts with strong sound associations (e.g., thunder). Human participants with the logopenic variant of primary progressive aphasia (lvPPA) performed a recognition task on words with strong associations in three modalities: Sound, Sight, and Manipulation. LvPPA participants had selective difficulty on Sound words relative to other modalities. Structural MRI analysis in lvPPA revealed gray matter atrophy in auditory association cortex, as defined functionally in a separate BOLD fMRI study of healthy adults. Moreover, lvPPA showed reduced gray matter density in the region of auditory association cortex that healthy participants activated when processing the same Sound words in a separate BOLD fMRI experiment. Finally, reduced gray matter density in this region in lvPPA directly correlated with impaired performance on Sound words. These findings support the hypothesis that conceptual memories are represented in the sensory and motor association cortices through which they are acquired. PMID- 22674274 TI - The optimality of sensory processing during the speed-accuracy tradeoff. AB - When people make decisions quickly, accuracy suffers. Traditionally, speed accuracy tradeoffs (SATs) have been almost exclusively ascribed to changes in the amount of sensory evidence required to support a response ("response caution") and the neural correlates associated with the later stages of decision making (e.g., motor response generation and execution). Here, we investigated whether performance decrements under speed pressure also reflect suboptimal information processing in early sensory areas such as primary visual cortex (V1). Human subjects performed an orientation discrimination task while emphasizing either response speed or accuracy. A model of choice behavior revealed that the rate of sensory evidence accumulation was selectively modulated when subjects emphasized accuracy, but not speed, suggesting that changes in sensory processing also influence the SAT. We then used fMRI and a forward encoding model to derive orientation-selective tuning functions based on activation patterns in V1. When accuracy was emphasized, the extent to which orientation-selective tuning profiles exhibited a theoretically optimal gain pattern predicted both response accuracy and the rate of sensory evidence accumulation. However, these relationships were not observed when subjects emphasized speed. Collectively, our findings suggest that, in addition to lowered response thresholds, the performance decrements observed during speeded decision making may result from a failure to optimally process sensory signals. PMID- 22674275 TI - Synaptic plasticity defect following visual deprivation in Alzheimer's disease model transgenic mice. AB - Amyloid-beta (Abeta)-induced changes in synaptic function in experimental models of Alzheimer's disease (AD) suggest that Abeta generation and accumulation may affect fundamental mechanisms of synaptic plasticity. To test this hypothesis, we examined the effect of APP overexpression on a well characterized, in vivo, developmental model of systems-level plasticity, ocular dominance plasticity. Following monocular visual deprivation during the critical period, mice that express mutant alleles of amyloid precursor protein (APPswe) and Presenilin1 (PS1dE9), as well as mice that express APPswe alone, lack ocular dominance plasticity in visual cortex. Defects in the spatial extent and magnitude of the plastic response are evident using two complementary approaches, Arc induction and optical imaging of intrinsic signals in awake mice. This defect in a classic paradigm of systems level synaptic plasticity shows that Abeta overexpression, even early in postnatal life, can perturb plasticity in cerebral cortex, and supports the idea that decreased synaptic plasticity due to elevated Abeta exposure contributes to cognitive impairment in AD. PMID- 22674276 TI - A critical cell-intrinsic role for serum response factor in glial specification in the CNS. AB - Astrocytes and oligodendrocytes play crucial roles in nearly every facet of nervous system development and function, including neuronal migration, synaptogenesis, synaptic plasticity, and myelination. Previous studies have widely characterized the signaling pathways important for astrocyte differentiation and unveiled a number of transcription factors that guide oligodendrocyte differentiation in the CNS. However, the identities of the transcription factors critical for astrocyte specification in the brain remain unknown. Here we show that deletion of the stimulus-dependent transcription factor, serum response factor (SRF), in neural precursor cells (NPCs) (Srf-Nestin cKO) results in nearly 60% loss in astrocytes and 50% loss in oligodendrocyte precursors at birth. Cultured SRF-deficient NPCs exhibited normal growth rate and capacity to self-renew. However, SRF-deficient NPCs generated fewer astrocytes and oligodendrocytes in response to several lineage-specific differentiation factors. These deficits in glial differentiation were rescued by ectopic expression of wild-type SRF in SRF-deficient NPCs. Interestingly, ectopic expression of a constitutively active SRF (SRF-VP16) in NPCs augmented astrocyte differentiation in the presence of pro-astrocytic factors. However, SRF-VP16 expression in NPCs had an inhibitory effect on oligodendrocyte differentiation. In contrast, mice carrying conditional deletion of SRF in developing forebrain neurons (Srf-NEX-cKO) did not exhibit any deficits in astrocytes in the brain. Together, our observations suggest that SRF plays a critical cell-autonomous role in NPCs to regulate astrocyte and oligodendrocyte specification in vivo and in vitro. PMID- 22674277 TI - Hearing an illusory vowel in noise: suppression of auditory cortical activity. AB - Human hearing is constructive. For example, when a voice is partially replaced by an extraneous sound (e.g., on the telephone due to a transmission problem), the auditory system may restore the missing portion so that the voice can be perceived as continuous (Miller and Licklider, 1950; for review, see Bregman, 1990; Warren, 1999). The neural mechanisms underlying this continuity illusion have been studied mostly with schematic stimuli (e.g., simple tones) and are still a matter of debate (for review, see Petkov and Sutter, 2011). The goal of the present study was to elucidate how these mechanisms operate under more natural conditions. Using psychophysics and electroencephalography (EEG), we assessed simultaneously the perceived continuity of a human vowel sound through interrupting noise and the concurrent neural activity. We found that vowel continuity illusions were accompanied by a suppression of the 4 Hz EEG power in auditory cortex (AC) that was evoked by the vowel interruption. This suppression was stronger than the suppression accompanying continuity illusions of a simple tone. Finally, continuity perception and 4 Hz power depended on the intactness of the sound that preceded the vowel (i.e., the auditory context). These findings show that a natural sound may be restored during noise due to the suppression of 4 Hz AC activity evoked early during the noise. This mechanism may attenuate sudden pitch changes, adapt the resistance of the auditory system to extraneous sounds across auditory scenes, and provide a useful model for assisted hearing devices. PMID- 22674278 TI - Computational modeling of collicular integration of perceptual responses and attention in microsaccades. AB - During visual fixation on a target object, our eyes are not motionless but generate slow fixational eye movements and microsaccades. Effects of visual attention have been observed in both microsaccade rates and spatial directions. Experimental results, however, range from early (<200 ms) to late (>600 ms) effects combined with cue-congruent as well as cue-incongruent microsaccade directions. On the basis of well characterized neural circuitry in superior colliculus, we construct a dynamical model of neural activation that is modulated by perceptual input and visual attention. Our results show that additive integration of low-level perceptual responses and visual attention can explain microsaccade rate and direction effects across a range of visual cueing tasks. These findings suggest that the patterns of microsaccade direction observed in experiments are compatible with a single dynamical mechanism. The basic principles of the model are highly relevant to the general problem of integration of low-level perception and top-down selective attention. PMID- 22674279 TI - Munc13-independent vesicle priming at mouse photoreceptor ribbon synapses. AB - Munc13 proteins are essential regulators of exocytosis. In hippocampal glutamatergic neurons, the genetic deletion of Munc13s results in the complete loss of primed synaptic vesicles (SVs) in direct contact with the presynaptic active zone membrane, and in a total block of neurotransmitter release. Similarly drastic consequences of Munc13 loss are detectable in hippocampal and striatal GABAergic neurons. We show here that, in the adult mouse retina, the two Munc13-2 splice variants bMunc13-2 and ubMunc13-2 are selectively localized to conventional and ribbon synapses, respectively, and that ubMunc13-2 is the only Munc13 isoform in mature photoreceptor ribbon synapses. Strikingly, the genetic deletion of ubMunc13-2 has little effect on synaptic signaling by photoreceptor ribbon synapses and does not prevent membrane attachment of synaptic vesicles at the photoreceptor ribbon synaptic site. Thus, photoreceptor ribbon synapses and conventional synapses differ fundamentally with regard to their dependence on SV priming proteins of the Munc13 family. Their function is only moderately affected by Munc13 loss, which leads to slight perturbations of signal integration in the retina. PMID- 22674281 TI - Amino-terminal ligands prolong NMDA Receptor-mediated EPSCs. AB - The amino-terminal domains of NMDA receptor subunits are important for receptor assembly and desensitization, and incorporate the high-affinity binding sites for zinc and ifenprodil. These amino-terminal ligands are thought of as subunit specific receptor inhibitors. However, multiple NMDA receptor subtypes contribute to EPSCs at wild-type hippocampal synapses. To understand the action of amino terminal ligands, we first used cultured hippocampal neurons from N2A and N2B knock-out mice. EPSCs from these neurons have properties that are consistent with N1/N2B and N1/N2A diheteromeric receptors, respectively. As expected, zinc reduced the EPSC peak amplitude from N2B KO neurons, but surprisingly also prolonged the deactivation, resulting in a marked redistribution of charge. Consistent with prolongation of the EPSC, zinc produced a longer latency to first opening of glutamate-bound receptors, which resulted in a decrease in the number of receptors that opened by the peak. Ifenprodil had similar effects on EPSCs from N2A KO neurons. In neurons from wild-type mice, zinc or ifenprodil reduced the EPSC peak, but only zinc caused significant charge redistribution, consistent with a small contribution of N1/N2B diheteromers in these neurons. Our results indicate that ligand binding to amino-terminal domains can alter the behavior of synaptic NMDA receptors under the nonequilibrium conditions of glutamate release during synaptic transmission. By prolonging EPSCs, amino-terminal ligands could markedly affect the computational properties of NMDA receptors and could potentially be exploited for therapeutic purposes. PMID- 22674280 TI - Dissociable influences of opiates and expectations on pain. AB - Placebo treatments and opiate drugs are thought to have common effects on the opioid system and pain-related brain processes. This has created excitement about the potential for expectations to modulate drug effects themselves. If drug effects differ as a function of belief, this would challenge the assumptions underlying the standard clinical trial. We conducted two studies to directly examine the relationship between expectations and opioid analgesia. We administered the opioid agonist remifentanil to human subjects during experimental thermal pain and manipulated participants' knowledge of drug delivery using an open-hidden design. This allowed us to test drug effects, expectancy (knowledge) effects, and their interactions on pain reports and pain related responses in the brain. Remifentanil and expectancy both reduced pain, but drug effects on pain reports and fMRI activity did not interact with expectancy. Regions associated with pain processing showed drug-induced modulation during both Open and Hidden conditions, with no differences in drug effects as a function of expectation. Instead, expectancy modulated activity in frontal cortex, with a separable time course from drug effects. These findings reveal that opiates and placebo treatments both influence clinically relevant outcomes and operate without mutual interference. PMID- 22674282 TI - Prolactin regulates tuberoinfundibular dopamine neuron discharge pattern: novel feedback control mechanisms in the lactotrophic axis. AB - Balance in the body's hormonal axes depends on feedback onto neuroendocrine hypothalamic neurons. This phenomenon involves transcriptional and biosynthetic effects, yet less is known about the potential rapid modulation of electrical properties. Here, we investigated this issue in the lactotrophic axis, in which the pituitary hormone prolactin is tonically inhibited by tuberoinfundibular dopamine (TIDA) neurons located in the hypothalamic arcuate nucleus. Whole-cell recordings were performed on slices of the rat hypothalamus. In the presence of prolactin, spontaneously oscillating TIDA cells depolarized, switched from phasic to tonic discharge, and exhibited broadened action potentials. The underlying prolactin-induced current is composed of separate low- and high-voltage components that include the activation of a transient receptor potential-like current and the inhibition of a Ca(2+)-dependent BK-type K(+) current, respectively, as revealed by ion substitution experiments and pharmacological manipulation. The two components of the prolactin-induced current appear to be mediated through distinct signaling pathways as the high-voltage component is abolished by the phosphoinositide 3-kinase blocker wortmannin, whereas the low voltage component is not. This first description of the central electrophysiological actions of prolactin suggests a novel feedback mechanism. By simultaneously enhancing the discharge and spike duration of TIDA cells, increased serum prolactin can promote dopamine release to limit its own secretion with implications for the control of lactation, sexual libido, fertility, and body weight. PMID- 22674283 TI - Humans mimicking animals: a cortical hierarchy for human vocal communication sounds. AB - Numerous species possess cortical regions that are most sensitive to vocalizations produced by their own kind (conspecifics). In humans, the superior temporal sulci (STSs) putatively represent homologous voice-sensitive areas of cortex. However, superior temporal sulcus (STS) regions have recently been reported to represent auditory experience or "expertise" in general rather than showing exclusive sensitivity to human vocalizations per se. Using functional magnetic resonance imaging and a unique non-stereotypical category of complex human non-verbal vocalizations-human-mimicked versions of animal vocalizations-we found a cortical hierarchy in humans optimized for processing meaningful conspecific utterances. This left-lateralized hierarchy originated near primary auditory cortices and progressed into traditional speech-sensitive areas. Our results suggest that the cortical regions supporting vocalization perception are initially organized by sensitivity to the human vocal tract in stages before the STS. Additionally, these findings have implications for the developmental time course of conspecific vocalization processing in humans as well as its evolutionary origins. PMID- 22674284 TI - An S-opsin knock-in mouse (F81Y) reveals a role for the native ligand 11-cis retinal in cone opsin biosynthesis. AB - In absence of their natural ligand, 11-cis-retinal, cone opsin G-protein-coupled receptors fail to traffic normally, a condition associated with photoreceptor degeneration and blindness. We created a mouse with a point mutation (F81Y) in cone S-opsin. As expected, cones with this knock-in mutation respond to light with maximal sensitivity red-shifted from 360 to 420 nm, consistent with an altered interaction between the apoprotein and ligand, 11-cis-retinal. However, cones expressing F81Y S-opsin showed an ~3-fold reduced absolute sensitivity that was associated with a corresponding reduction in S-opsin protein expression. The reduced S-opsin expression did not arise from decreased S-opsin mRNA or cone degeneration, but rather from enhanced endoplasmic reticulum (ER)-associated degradation of the nascent protein. Exogenously increased 11-cis-retinal restored F81Y S-opsin protein expression to normal levels, suggesting that ligand binding in the ER facilitates proper folding. Immunohistochemistry and electron microscopy of normal retinas showed that Mueller cells, which synthesize a precursor of 11-cis-retinal, are closely adjoined to the cone ER, so they could deliver the ligand to the site of opsin synthesis. Together, these results suggest that the binding of 11-cis-retinal in the ER is important for normal folding during cone opsin biosynthesis. PMID- 22674285 TI - Ardisianone, a natural benzoquinone, efficiently induces apoptosis in human hormone-refractory prostate cancers through mitochondrial damage stress and survivin downregulation. AB - BACKGROUND: Increasing evidence suggests that mitochondria play a central role in regulating cell apoptosis. Survivin, an inhibitor of apoptosis protein (IAP) family member, mediates resistance to cancer chemotherapy particularly in prostate cancers. Therefore, development of anticancer agents targeting mitochondria and survivin is a potential strategy. METHOD: Cell proliferation was examined by sulforhodamine B, CFSE staining, and clonogenic assays. Mitochondrial membrane potential (DeltaPsi(m) ) and reactive oxygen species (ROS) were detected by flow cytometric analysis. Protein expression was detected by Western blot. RNA levels were examined by reverse transcription polymerase chain reaction assay. Overexpression of constitutively active Akt was also used in this study. RESULTS: Ardisianone, a natural benzoquinone derivative, displayed anti-proliferative and apoptotic activities against human hormone-refractory prostate cancer cells (HRPC), PC-3, and DU-145. Ardisianone dramatically induced mitochondrial damage, identified by downregulation of Bcl-2 family proteins, ROS production, and loss of DeltaPsi(m) . Ardisianone also inhibited Akt and mTOR/p70S6K pathways and induced a fast downregulation of survivin, leading to activation of mitochondria involved caspase cascades. Overexpression of constitutively active Akt partly rescued ardisianone-mediated apoptotic signaling cascades. Furthermore, a long term treatment of ardisianone caused an increase of endoplasmic reticulum (ER) stress, upregulation of cIAP1 and cIAP2, and apoptosis-inducing factor (AIF) mediated caspase-independent apoptosis. CONCLUSIONS: The data suggest that the ardisianone induces apoptosis in human prostate cancers through mitochondrial damage stress, leading to the inhibition of mTOR/p70S6K pathway, downregulation of Bcl-2 family members, degradation of survivin, and activation of caspase cascades. The data provide evidence supporting that ardisianone is a potential anticancer agent against HRPCs. PMID- 22674286 TI - Thrombin induces epidermal growth factor receptor transactivation and CCL2 expression in human osteoblasts. AB - OBJECTIVE: Thrombin is a key factor involved in the stimulation of fibrin deposition, angiogenesis, and proinflammatory processes. Abnormalities in these processes are primary features of rheumatoid arthritis (RA). The aim of this study was to investigate the intracellular signaling pathways involved in thrombin-induced CCL2 expression in human osteoblasts. METHODS: Thrombin-mediated CCL2 expression was assessed by quantitative polymerase chain reaction and enzyme linked immunosorbent assay. The mechanisms of action of thrombin in different signaling pathways were studied using Western blotting. Knockdown of protease activated receptor (PAR) protein was achieved by small interfering RNA (siRNA) transfection. Chromatin immunoprecipitation assays were used to study in vivo binding of c-Jun to the CCL2 promoter. Transient transfection was used to examine activator protein 1 (AP-1) activity. RESULTS: Stimulation of human primary osteoblasts and MG-63 cells with thrombin induced CCL2 expression. PAR-1-specific siRNA (but not other PAR siRNA) was involved in thrombin-mediated up-regulation of CCL2. Thrombin-mediated CCL2 production was attenuated by the thrombin inhibitor PPACK, the protein kinase Cdelta (PKCdelta) inhibitor rottlerin, the c Src inhibitor PP2, epidermal growth factor receptor (EGFR) inhibitor AG-1478, MEK inhibitors PD98059 and U0126, or AP-1 inhibitors curcumin and tanshinone IIA. Stimulation of cells with thrombin increased PKCdelta, c-Src, EGFR, MEK, and ERK activation. Treatment of osteoblasts with thrombin also increased c-Jun phosphorylation, AP-1 luciferase activity, and c-Jun binding to the AP-1 element on the CCL2 promoter. CONCLUSION: Our results suggest that the interaction between thrombin and PAR-1 increases CCL2 expression in human osteoblasts via the PKCdelta/c-Src/ EGFR transactivation/MEK/ERK/c-Jun/AP-1 pathway. PMID- 22674287 TI - Integration of binocular optic flow in cervical neck motor neurons of the fly. AB - Global visual motion elicits an optomotor response of the eye that stabilizes the visual input on the retina. Here, we analyzed the neck motor system of the blowfly to understand binocular integration of visual motion information underlying a head optomotor response. We identified and characterized two cervical nerve motor neurons (called CNMN6 and CNMN7) tuned precisely to an optic flow corresponding to pitch movements of the head. By means of double recordings and dye coupling, we determined that these neurons are connected ipsilaterally to two vertical system cells (VS2 and VS3), and contralaterally to one horizontal system cell (HSS). In addition, CNMN7 turned out to be connected to the ipsilateral CNMN6 and to its contralateral counterpart. To analyze a potential function of this circuit, we performed behavioral experiments and found that the optomotor pitch response of the fly head was only observable when both eyes were intact. Thus, this neural circuit performs two visuomotor transformations: first, by integrating binocular visual information it enhances the tuning to the optic flow resulting from pitch movements of the head, and second it could assure an even head declination by coordinating the activity of the CNMN7 neurons on both sides. PMID- 22674288 TI - Olfactory dysfunctions in neurodegenerative disorders. AB - Olfactory dysfunction is a common symptom in the patients with neurodegenerative disorders, particularly in Parkinson's disease (PD) and Alzheimer's disease (AD). Recently, studies of olfactory dysfunction have focused on its potential as a medication-independent biomarker for disease progression and as an early indicator for the diagnosis of neurodegenerative disorders. In the past decades, great achievements have been obtained in elucidating the neuroanatomy and the function of olfactory system, yet the pathogenesis of olfactory dysfunction in neurodegenerative disorders remains elusive. The neuropathologic changes of olfactory dysfunction in neurodegenerative diseases may involve the olfactory epithelium, olfactory bulb, primary olfactory cortices, and their secondary targets changes. This article summarizes the up-to-date knowledge on pathophysiological changes of the olfactory system in neurodegenerative disorders and attempts to find the association between olfactory dysfunction and neurodegenerative disorders. PMID- 22674289 TI - Pancreatoduodenectomy for melanoma with metastasis to the common bile duct. AB - Melanoma with metastasis to the common bile duct is relatively rare. This report presents the case of a 56-year-old Japanese male that showed an abnormal laboratory profile 18 months after resection of a skin melanoma occurring on the left fifth finger. The cytology of bile obtained by endoscopic retrograde cholangiopancreatography yielded a diagnosis of melanoma with metastasis to the common bile duct. Surgery revealed melanoma within the distal common bile duct. There were no other secondary metastases in the abdomen and a radical pancreatoduodenectomy was performed. The patient survived for 13 months without any signs of recurrence and died of progressive systemic metastatic melanoma 34 months after surgery. Therefore, radical surgical resection appears to be effective for the prolongation of survival in cases of melanoma with metastasis to the common bile duct. PMID- 22674290 TI - Value of cytologic Papanicolaou smears and polymerase chain reaction screening for human papillomavirus DNA in detecting anal intraepithelial neoplasia: comparison with histology of a surgical sample. AB - BACKGROUND: The performance of cytologic screening and its correlation with histology and polymerase chain reaction (PCR) detection of human papillomavirus (HPV) DNA have not been evaluated in populations with a low prevalence of anal intraepithelial neoplasia (AIN). The objective of the current study was to analyze the significance of abnormal smears relative to the histology and PCR detection of HPV DNA. METHODS: A cytologic smear and a viral sample were taken in 300 consecutive patients undergoing surgery (Milligan-Morgan hemorrhoidectomy and/or fissurectomy) who gave their informed consent. RESULTS: The cytologic smear was normal in 216 of 290 patients (74.5%). Four high-grade and 19 low-grade intraepithelial neoplastic lesions were identified. In 5 patients, high-grade lesions could not be excluded, 30 lesions were of undetermined significance, and there were 16 cellular modifications with a non-neoplastic appearance. The PCR test for HPV was positive in 18.7% of patients, and a high-risk genotype was identified in 63.6% of positive samples. Histologic examination of the surgical samples was normal in 92.3% of patients. The 23 AIN samples were distributed as follows: 13 grade 1 AIN (AIN1), 6 AIN2, and 4 AIN3. The sensitivity of cytologic smears and PCR for detecting AIN was 56% and 60.8%, respectively, and specificity was 77% and 84.5%, respectively. Combining the 2 tests increased sensitivity to 78% but decreased specificity to 68%. CONCLUSIONS: Compared with a large surgical sample, anal cytologic Papanicolaou smears and HPV PCR exhibited sensitivity and specificity that varied, depending on the risk of HPV infection and AIN. Positive HPV DNA screening increased with AIN grade, and high-risk HPV testing was particularly helpful. PMID- 22674291 TI - Prediagnostic concentrations of plasma genistein and prostate cancer risk in 1,605 men with prostate cancer and 1,697 matched control participants in EPIC. AB - PURPOSE: Data from prospective epidemiological studies in Asian populations and from experimental studies in animals and cell lines suggest a possible protective association between dietary isoflavones and the development of prostate cancer. We examined the association between circulating concentrations of genistein and prostate cancer risk in a case-control study nested in the European Prospective Investigation into Cancer and Nutrition. METHODS: Concentrations of the isoflavone genistein were measured in prediagnostic plasma samples for 1,605 prostate cancer cases and 1,697 matched control participants. Relative risks (RRs) for prostate cancer in relation to plasma concentrations of genistein were estimated by conditional logistic regression. RESULTS: Plasma genistein concentrations were not associated with prostate cancer risk; the multivariate relative risk for men in the highest fifth of genistein compared with men in the lowest fifth was 1.00 (95 % confidence interval: 0.79, 1.27; p linear trend = 0.82). There was no evidence of heterogeneity in this association by age at blood collection, country of recruitment, or cancer stage or histological grade. CONCLUSION: Plasma genistein concentration was not associated with prostate cancer risk in this large cohort of European men. PMID- 22674292 TI - Socioeconomic status, healthcare density, and risk of prostate cancer among African American and Caucasian men in a large prospective study. AB - OBJECTIVES: The purpose of this study was to separately examine the impact of neighborhood socioeconomic deprivation and availability of healthcare resources on prostate cancer risk among African American and Caucasian men. METHODS: In the large, prospective NIH-AARP Diet and Health Study, we analyzed baseline (1995 1996) data from adult men, aged 50-71 years. Incident prostate cancer cases (n = 22,523; 1,089 among African Americans) were identified through December 2006. Lifestyle and health risk information was ascertained by questionnaires administered at baseline. Area-level socioeconomic indicators were ascertained by linkage to the US Census and the Area Resource File. Multilevel Cox models were used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs). RESULTS: A differential effect among African Americans and Caucasians was observed for neighborhood deprivation (p-interaction = 0.04), percent uninsured (p-interaction = 0.02), and urologist density (p-interaction = 0.01). Compared to men living in counties with the highest density of urologists, those with fewer had a substantially increased risk of developing advanced prostate cancer (HR = 2.68, 95 % CI = 1.31, 5.47) among African American. CONCLUSIONS: Certain socioeconomic indicators were associated with an increased risk of prostate cancer among African American men compared to Caucasians. Minimizing differences in healthcare availability may be a potentially important pathway to minimizing disparities in prostate cancer risk. PMID- 22674294 TI - Evolution of Cancer Control P.L.A.N.E.T.: moving research into practice. AB - Evidence-based interventions (EBIs) are not broadly implemented, despite widespread availability of programs, policies, and guidelines. Systematic processes for integrating EBIs with community preference remain challenging for cancer control and prevention, as well as other areas. The Cancer Control P.L.A.N.E.T. (P.L.A.N.E.T) Web portal provides a platform to access data, EBIs, and resources to foster local partnerships and assist public health researchers and practitioners design, implement, and evaluate evidence-based cancer control programs. This article summarizes the evolution of P.L.A.N.E.T. and describes effective and innovative Web 2.0 strategies to increase Web visits, create more interactive platforms for researchers and practitioners to integrate evidence based resources, community preferences, and the complex context in which programs and policies are implemented. Lessons learned could benefit public health settings and reach low-income, high-risk communities. Researchers, community practitioners, and government partnerships should continue to develop and test innovative ways to address pressing issues in cancer control, health disparities, and health delivery. PMID- 22674293 TI - The association of diabetes with breast cancer incidence and mortality in the Long Island Breast Cancer Study Project. AB - PURPOSE: Diabetes has been associated with increased risk of breast cancer in a number of epidemiologic studies, but its effects on survival among women diagnosed with breast cancer have been examined less frequently. Importantly, prior investigations have rarely considered the influence of factors associated with diabetes such as obesity, age at diabetes diagnosis, duration of diabetes, or diabetes treatments. METHODS: We evaluated the effect of self-reported diabetes on breast cancer incidence and mortality in the Long Island Breast Cancer Study Project, which includes 1,447 breast cancer cases and 1,453 controls. Follow-up data for all-cause (n = 395) and 5-year breast cancer specific mortality (n = 104) through December 2005 were determined for case women from the National Death Index. Adjusted logistic regression and Cox proportional hazards models were used to estimate odds ratios (OR) and hazards ratios (HR), respectively. RESULTS: Postmenopausal women with diabetes were at increased risk of developing breast cancer [OR = 1.35; 95 % confidence interval (CI) = 0.99 1.85], as were those who were not of white race regardless of menopausal status [OR = 3.89; 95 % CI = 1.66-9.11]. Among case women, diabetes was associated with a modestly increased risk of death from all causes [HR = 1.65; 95 % CI = 1.18 2.29], an association that was stronger in women who were obese at breast cancer diagnosis [HR = 2.49; 94 % CI = 1.58-3.93]. In analyses restricted to diabetics, there was no statistically significant effect of duration of diabetes or type of treatment on breast cancer incidence or mortality. CONCLUSIONS: Our findings suggest that diabetes may increase incidence of breast cancer in older women and non-whites, and mortality due to all causes. PMID- 22674295 TI - The educational claims of zoos: where do we go from here? AB - Zoos exude a certain self-confidence regarding their roles as education providers. Indeed, the education outputs of zoos are, at face value, pretty impressive, with most investing in learning opportunities for leisure visitors, education groups and in some cases, as part of their in situ programs. However, these outputs are not necessarily reliable indicators of the educational achievements of zoos. Quantity does not necessarily equate to quality, just as outputs do not necessarily lead to outcomes. Zoo-accreditation organizations such as the AZA and EAZA offer us clear insight into the strategic vision underpinning the education goals for zoo visitors; a heightened appreciation of the value of biodiversity and a connectedness with the natural world. Unsurprisingly, most zoos have educational goals that ally neatly with the vision of their respective accreditation body. Consequently, we are left with fairly narrow, top-down educational goals. This does not necessarily sit well with what we know about the unpredictability of "free choice" learning in environments such as zoos and aquariums, or what is known about public science communication. Research that seeks to explore the impacts of zoo visits often focuses on evaluating performance based on educational goals and the findings are used as a means of providing evidence of institutional achievement. However, any visitor outcome that falls outside of this narrow range could well be missed by the research. In this article, we propose that research that takes unpredictable and unexpected outcomes into account is necessary and overdue. PMID- 22674296 TI - Interleukin genes and associations with colon and rectal cancer risk and overall survival. AB - Interleukins are a group of cytokines that contribute to growth and differentiation, cell migration, and inflammatory and anti-inflammatory responses by the immune system. In our study, we examined genetic variation in genes from various anti-inflammatory and proinflammatory interleukins to determine association with colon and rectal cancer risk and overall survival. Data from two population-based incident studies of colon cancer (1,555 cases and 1,956 controls) and rectal cancer (754 cases and 954 controls) were used. After controlling for multiple comparisons, single nucleotide polymorphisms (SNPs) from four genes, IL3, IL6R, IL8, IL15, were associated with increased colon cancer risk, and CXCR1 and CXCR2 were significantly associated with increased rectal cancer risk. Only SNPs from genes within the IL-8 pathway (IL8, CXCR1 and CXCR2) showed a significant association with both colon and rectal cancer risk. Several SNPs interacted significantly with IL8 and IFNG SNPs and with aspirin/non steroidal anti-inflammatory drug (NSAID), cigarette smoking, estrogen use and BMI. For both colon and rectal cancer, increasing numbers of risk alleles were associated with increased hazard of death from cancer; the estimated hazard of death for colon cancer for the highest category of risk alleles was 1.74 (95% confidence interval [CI] 1.18-2.56) and 1.96 (95% CI 1.28-2.99) for rectal cancer. These data suggest that interleukin genes play a role in risk and overall survival for colon and rectal cancer. PMID- 22674297 TI - Correlation between age and Chromogranin A determination in prostate diseases. AB - INTRODUCTION: Serum levels of Chromogranin A (CgA) were measured in consecutive patients with prostate diseases in order to evaluate the impact of age on CgA diagnostic significance. MATERIALS AND METHODS: Serum levels of CgA were determinated in 217 consecutive patients immediately before prostate biopsy: CgA differences between cases (prostate cancer PC) and control (benign prostatic hyperplasia BPH) were analyzed, and CgA performance in prediction of PC was compared with age and standard diagnostic tools. CgA values were also analyzed in patients affected by PC, and compared with age and standard prognostic parameters. RESULTS: At multivariate analysis, CgA approaches a statistically significant value as independent predictor of PC and positively correlates with age. In PC group, CgA positively correlates with age, while no correlations are found with PSA, Gleason score or stage of disease. CONCLUSIONS: Age, correlating with CgA values in overall population and in PC subgroup, emerged as a confounding factor in CgA determination. Serum CgA has not been demonstrated as a diagnostic marker of PC being only a marker of neuroendocrine differentiation. Cga values did not correlate with other clinical prognostic factors, except age, in untreated-naive PC. PMID- 22674298 TI - The over expression of cathelicidin peptide LL37 in head and neck squamous cell carcinoma: the peptide marker for the prognosis of cancer. AB - The over expression of LL37, an antimicrobial peptide belonging~to the cathelicidin family has implication in the progression of human malignancy but the exact role is still not clear. This study aims to elucidate the correlation of LL37 with Head and Neck Squamous Cell Carcinoma (HNSCC) and the consequences of radiotherapy on it. The LL37 levels were quantified in serum samples of control and HNSCC patients at pre-RT, during-RT and post-RT using a real time Surface Plasmon Resonance technology and ELISA. The LL37 of 50 HNSCC patients was significantly (p < 0.0001) threefold higher than the 25 controls and declined with respect to radiation therapy (p < 0.0001) supporting its candidature as a prognostic marker in HNSCC. PMID- 22674299 TI - Hypermethylation of collagen alpha2 (I) gene (COL1A2) is an independent predictor of survival in head and neck cancer. AB - OBJECTIVES: Collagen production plays a role in the development of tumors from cancer cells. The aim of the present study is to examine the involvement of epigenetic alteration of Collagen alpha2 (I) (COL1A2) gene expression in cases of head and neck squamous cell carcinoma (HNSCC). METHODS: COL1A2 expression was examined in a panel of cell lines using RT-PCR. The methylation status of the COL1A2 promoter was studied using bisulfate sequencing and methylation-specific PCR (MSP). RESULTS: COL1A2 expression was absent in 6 of 11 (54.5%) UM-SCC cell lines, whereas three nonmalignant cell lines had stable expressions. MSP analysis showed that 46/98 (46.9%) contained methylated alleles. COL1A2 methylation was significantly correlated with tumor size (P = 0.041), lymph node status (P = 0.008), tumor stage (P = 0.011), H-cadherin methylation (P = 0.039) and disease free survival (P = 0.005). On multivariate Cox proportional hazard regression, which included age, sex, smoking status, and alcohol exposure, both tumor stage and COL1A2 methylation remained independent prognostic factors. CONCLUSIONS: This study suggests that CpG hypermethylation is a likely mechanism of COL1A2 gene inactivation, supporting the hypothesis that the COL1A2 gene may play a role in the tumorigenesis of HNSCC and may serve as an important biomarker. PMID- 22674300 TI - Altered desialylated plasma N-glycan profile in patients with non-small cell lung carcinoma. AB - Successful therapy of the non-small cell lung carcinoma (NSCLC) depends on its early detection, and non-invasive detection methods are preferred. As plasma proteins are modified by N-linked glycosylation, we tested the importance of the N-glycan profile in diagnosing and prognosticating NSCLC. We analysed desialylated plasma samples from 75 NSCLC patients, and 71 healthy individuals by the high-throughput DNA sequencer-based carbohydrate analytical profiling technique. We detected alterations in the levels of several N-glycans in NSCLC patients. Total alpha-1,6-core fucosylated biantennaries (NGA2F, NG1A2F, NA2F) and total bisecting alpha-1,6-core fucosylated biantennaries (NGA2FB, NA2FB) were reduced in NSCLC patients, whereas the branching alpha-1,3-fucosylated triantennary N-glycan (NA3FB) was increased. Best diagnostic accuracy was identified for NG1A2F. NSCLC patients with TNM stage I stage did not show further differences, but patients with higher stages did (TNM II to IV). Those patients additionally had a reduced level in the alpha-1,6-core fucosylated structure NA2F with parallel increase in the non-fucosylated structure NA2. In this regard, NSCLC patients with a relatively low amount of NA2 per NA2F had a better three year survival than patients with high amount. NSCLC patients show an altered N glycan profile of plasma proteins that may be regarded as a supportive tool for cancer diagnosis. PMID- 22674301 TI - The prognostic values of CA125, CA19.9, NSE, AND SCC for stage I NSCLC are limited. AB - OBJECTIVE: Amongst the current detections of tumor markers, measurement of serum tumor markers is the most convenient and the safest way. However, there are few promising serum tumor markers with confirmed prognostic value in NSCLC (non-small cell lung cancer, NSCLC). Therefore, scientists only grafted the useful tumor markers, such as CA125, CA19.9, NSE, SCC, CEA and CYFRA21.1 which have been found in other solid tumors. However, previous reports about this issue remain controversial. This study is to analyze the prognostic values of these 6 markers in stage I NSCLC. METHODS: One hundred and sixty four patients with stage I NSCLC who underwent operation by single-surgery-team in Department I of Thoracic Surgery, Peking University Cancer Hospital between March 2000 and March 2011 were included. These patients had measurement of CA125, CA19.9, NSE, SCC, CEA and CYFRA21.1 using electrochemiluminescence immunoassay one week before operation. The relationship between the level of these 6 tumor markers and long term survival rate was analyzed. RESULTS: The positive rate for CA125, CA19.9, NSE, SCC, CEA and CYFRA 21.1 in the 121 adenocarcinoma patients was 5.7%, 5.7%, 18.3%, 5.3%, 18.3%, and 20.7% respectively; whereas 3.1%, 2.6%, 23.8%, 26.8%, 14.0%, and 42.9% in 43 non-adenocarcinoma patients, respectively. In univariate analysis, the overall 5 year survival rate of patients with elevated CYFRA21.1 level was lower than that of patients with normal level in ADC subgroup (54.5% vs. 83.8%, p < 0.05) and in all 164 cases (49.5% vs. 76.4%, p < 0.05). In multivariate analysis, the level of CYFRA21.1 was an independent prognostic factor. But the other 5 markers didn't show significant prognostic value. CONCLUSIONS: We found that the prognostic values of CA125, CA19.9, NSE, and SCC for stage I NSCLC are limited. CYFRA21.1 might be a hopeful prognostic serum tumor marker for stage I NSCLC. PMID- 22674302 TI - Association of D4-GDI expression with breast cancer progression. AB - D4-GDI is a key regulator of Rho GTPases that have been implicated in several aspects of breast tumorigenesis. We have previously found that D4-GDI was selectively expressed in breast cancer cell lines over normal mammary epithelial cells [45]. In this study, we investigated the expression level of D4-GDI in breast tumor specimens (n = 165) by immunohistochemistry using a validated antibody that specifically recognizes the full-length D4-GDI protein. D4-GDI was predominantly expressed in the luminal cells of the duct in contrast to the myoepithelial cells of the outer layer. The percentage of D4-GDI positive samples were found to be higher in the early stages of breast cancers followed by a significant decrease in malignant tumors and metastatic lesions when compared to normal breast tissues (p < 0.01). Analysis of matched samples confirmed the lower expression of D4-GDI in malignant tumors than normal adjacent tissues, while there was no further decrease in metastatic lesions. These results suggest that D4-GDI may function as a biphasic regulator of breast cancer progression and metastasis. PMID- 22674303 TI - Use of quantitative shotgun proteomics to identify fibronectin 1 as a potential plasma biomarker for clear cell carcinoma of the kidney. AB - BACKGROUND: Early detection would be one of the most effective means to improve the outcome of renal cell carcinoma (RCC). We searched for a new plasma marker for RCC using a label-free quantitative shotgun proteomics method. METHODS: Plasma proteins were digested by trypsin, and the resulting peptides were analyzed by 2-Dimensional Image Converted Analysis of Liquid chromatography mass spectrometry (2DICAL). An identified biomarker candidate was subjected to validation using the Amplified Luminescent Proximity Homogeneous Assay (AlphaLISA). RESULTS: Among a total of 23,407 independent MS peaks, we found that the mean intensity of 59 peaks significantly differed between 20 clear cell RCC patients and 20 healthy controls. MS/MS spectra from 16 of the 59 peaks matched the amino acid sequences of the fibronectin 1 (FN1) gene product. The increased plasma level of FN1 in RCC patients was validated in a cohort of in 77 patients and 130 healthy controls (p < 0.0001). CONCLUSIONS: The FN1 is considered to be a promising biomarker candidate for clear cell RCC. Furthermore, AlphaLISA is an alternate to the conventional enzyme-linked immunosorbent assay and should prove useful for the rapid validation of biomarker candidates. PMID- 22674304 TI - Post-transcriptional regulation of O(6)-methylguanine-DNA methyltransferase MGMT in glioblastomas. AB - BACKGROUND: The DNA repair enzyme O(6)-methylguanine-DNA methyltransferase (MGMT) confers therapeutic resistance to DNA alkylating agents, including temozolomide. It is largely believed that MGMT promoter methylation is associated with down regulation of MGMT transcription and corresponding protein expression, thereby predisposing tumor cells to the toxic effect of temozolomide. Here we rigorously examined this underlying assumption. METHODS: We examined the correlation between MGMT promoter methylation, transcription, and protein expression using The Cancer Genome Atlas (TCGA) glioblastoma database as well as an independent collection of glioblastoma specimens. RESULTS: In both analyses, we found that MGMT promoter methylation status correlates well with low MGMT mRNA levels (p = 0.04). On the other hand, glioblastomas with unmethylated MGMT promoters exhibited a wide range of MGMT mRNA expression. Intriguingly, the MGMT mRNA levels correlated poorly with MGMT protein levels by Western blotting (R(2) = 0.04, p = 0.34) or by ImmunoHistoChemical (IHC) stain quantitation (R(2) = 0.02, p = 0.50). To exclude the possibility that the poor correlation was due to substandard specimens, we determined the mRNA and protein levels of Colony Stimulating Factor 1 (CSF1), a gene previously shown to exhibit excellent mRNA/protein correlation. In contrast to MGMT, the mRNA level of CSF1 correlated well with the protein level (R(2) = 0.47, p = 0.001). Importantly, long-term passaged glioblastoma cell lines with comparable MGMT transcript levels differed in MGMT protein levels, suggesting mechanisms of post-transcriptional regulation. Accordingly, the correlation between MGMT promoter methylation and MGMT protein expression was poor (p = 0.27). In silico analysis predicted potential binding sites for several miRNA within the 3'UTR of MGMT, suggesting a mechanism for the post-transcriptional of MGMT. CONCLUSION: Our results suggest mechanisms such as miRNA mediated regulation for post-transcriptional regulation of MGMT. Identification of these mechanisms should enhance the value of MGMT based prognostic or predictive biomarker strategies. PMID- 22674306 TI - [Make your own diagnosis: part I]. PMID- 22674307 TI - [Direct costs and hospital morbimortality impact from preventable adverse drug events]. AB - INTRODUCTION: Implementing pharmacovigilance activities consists of monitoring and assessment of activities related to medical attention. However, additional data are necessary to identify conditions where care quality can be improved. Therefore, a focus on adverse drug events analysis from a prevention and economic perspective is needed, with emphasis on its local impact. OBJECTIVE: Preventable adverse drug events were summarized to establishing their impact on morbidity and mortality, as well as to estimate the ensuing economic burden. MATERIALS AND METHODS: The data were gathered from a level 3 hospital (high complexity), located in Bogota, Colombia, where specific pharmacovigilance activities were recorded in 2007. Patient charts were reviewed to characterize adverse drug events according to their causality, severity and preventability. Direct costs were estimated by grouping diagnostic tests, length of hospitalization, procedures and additional drugs required. RESULTS: The charts of 283 patients and 448 reports were analyzed. These data indicated that 24.8% of adverse drug events were preventable and that an associated mortality of 1.1% had occurred. The associated direct costs were between USD $16,687 and $18,739. Factors more commonly associated with preventability were drug-drug interactions, as well as inappropriate doses and unsuitable frequencies at which the drugs were administrated. CONCLUSIONS: The data recommended that actions be taken to decrease preventable adverse drug events, because of negative impact on patient's health, and unnecessary consumption of healthcare resources. PMID- 22674308 TI - [Prevalence of Mammomonogamus laryngeus(Strongylida:Syngamidae) nematodes in a bovine slaughterhouse]. AB - INTRODUCTION: Mammomonogamus laryngeus is a nematode parasite that is usually found in the larynx of mammals in the tropics, especially in cattle, sheep and cats. OBJECTIVE: The prevalence of M. laryngeus was determined in cattle brought to an abattoir as an indicator of its prevalence in the general population. Materials and methods. The present study was undertaken in the municipality of La Tebaida, Quindio, Colombia, to determine the presence of M. laryngeus infection in cattle brought to a local abattoir between December and February 2009. The tracheae and lungs of 500 slaughtered cattle were examined. RESULTS: Parasite prevalence was 14.8% (n=74). The majority of worms were located on aryteno epiglottic folds, but never in the tracheae or bronchi. The infection rate was highest (47%) in 2 to 2.5 year old animals. In infected animals, an average of 6.4 parasite pairs was found, with higher numbers in older animals. The prevalence of infection in cattle was greater than seen in the provinces of Valle del Cauca (10.0%), Quindio(3,0%) pr Caqueta (1.2%). CONCLUSIONS: Reports of this parasite in cattle indicate its circulation throughout Colombia and recommend surveillance studies where cattle are raised and prepared for human consumption. PMID- 22674309 TI - [Impact of a waste disposal site on adult respiratory health]. AB - INTRODUCTION: This study evaluated the impact of the presence of a dump on respiratory health in adults older than 50 years of age, living in its area of influence. MATERIALS AND METHODS: A cohort study was conducted with 313 adults older than 50 years of age living near the Navarro Dump (Cali, Colombia) and compared with 359 adults in an unexposed area. Each was examined monthly during a 6 month period to compare the incidence of respiratory symptoms and alterations in peak expiratory flow. RESULTS: Exposure to the Navarro Dump was associated with occurrence of respiratory symptoms (odds ratio=1.25, 95% C.I. 1.01-1.56), in particular with mild respiratory symptoms (odds ratio=1.28, 95% C.I. 0.98-1.66). This result was obtained after adjusting for age, sex, education level, humidity, health insurance, comorbidity, smoking and previous occupational exposure. A higher recurrence of symptoms was found in adults in the area of exposure (correlation coefficient=0.29, 95% C.I. 0.23-0.33, p<0.001) and a significant reduction in the lung function defined by peak expiratory flow; the average decrease was 15.2 L/min (95% C.I. -30.2 to +0.22). CONCLUSION: Independent of potential confounding factors, the respiratory health of adults exposed to the Navarro Dump was affected and exhibited an increased occurrence and recurrence of mild respiratory symptoms as well as decreased lung function. PMID- 22674310 TI - Cytotoxic effect of some natural compounds isolated from Lauraceae plants and synthetic derivatives. AB - INTRODUCTION: The antiproliferative effect of eleven neolignans, two lignans and one diterpene isolated from three Lauraceae plants, four benzofurans and two bicyclooctanes synthetic derivatives was evaluated in vitro on a set of five human cancer cells from solid tumors with a high incidence in Colombia. OBJECTIVE: To evaluate the cytotoxic effect of twenty compounds on the tumor cell lines HeLa, A-549, Hep-2, PC-3, and MCF-7. MATERIALS AND METHODS. Fourteen natural compounds were isolated by chromatographic techniques from three native Colombian plants (Pleurothyrium cinereum, Ocotea macrophylla and Nectandra amazonum), whose structures were established by spectroscopic methods; six synthetic derivatives were prepared by oxyarylation and diazomethane methylation. Antiproliferative effect and cell recovery were performed by means of in vitro treatment of tumor cell lines with test compounds, evaluating cell viability by resazurin staining. RESULTS: Among test compounds, only neolignans ocophyllal A, cinerin D, kaurenoic acid, two benzofuran-derivatives, and synthetic (-)-cinerin A were found to have antiproliferative effect at different levels. Bicyclooctanoids as well as kaurenoic acid exhibited activity against all human cancer cells while benzofuranoids showed selective activity against HeLa. Furthermore, compounds (-)-cinerin A and kaurenoic acid exhibited total lethal effect against all-five cell lines and PC-3, Hep-2, and A549 cell lines, respectively. CONCLUSION: Test compounds exhibiting antiproliferative activity showed interesting results, which would promote their use as lead compounds on further studies for anticancer agents development. PMID- 22674312 TI - [Biological pollution and its relationship with respiratory symptoms indicative of asthma, Bucaramanga, Colombia]. AB - INTRODUCTION: Indoorair pollution may play an important role in development and exacerbation of asthma in children. OBJECTIVE: The association between the presence of indoor biological contaminants and respiratory symptoms related to asthma was assessed in preschool children. Materials and methods. This cross sectional study was undertaken in Bucaramanga, Colombia, and included children <7 years of age living in two urban areas of with different levels of outdoor air pollution. The 678 children were an average of 3.5 years of age. Respiratory symptoms indicative of asthma and indoor air pollutants were assessed by previously validated questionnaires.. Biological samples potentially containing mites and fungi were collected by standardized laboratory methods. The log binomial regression model was used for multivariate analysis, using adjusted prevalence ratios (PR). RESULTS: The prevalence of asthmatic respiratory symptoms was 8.0%; (95% C.I: 5.6-9.6), without significant differences between the two areas. Binomial model analysis showed that asthma symptoms were associated with mites (PR 1.78; 95% C.I. 1.0-3.0), Acremonium sp (PR 6.24; 95 C.I.: 3.8-10.0) and a history of child pneumonia (PR 4.0; 95% C.I. 2.5-6.4), allergic rhinitis (PR 1.9; 95% C.I.: 1.2-3.1), prematurity (PR 3.4; 95% C.I. 1.8-6.5), parents with asthma (PR 2.6; 95% C.I. 1.4-5.0) and pet ownership (PR 0.4; 95% C.I. 0.2-0.9). CONCLUSIONS: The indoor exposure to biological contaminants (dust mites and fungi), history of prematurity, pneumonia, rhinitis and family history of asthma increased the occurence of symptoms suggestive of asthma in young children. PMID- 22674311 TI - Histoplasmosis: results of the Colombian national survey, 1992-2008. AB - INTRODUCTION: Histoplasmosis, a fungal disorder characterized by a wide spectrum of manifestations that range from subclinical infections to disseminated processes, affects both immunocompetent and immunosuppressed individuals. Histoplasmosis is not a reportable disease in Colombia and consequently, a survey was designed to collect histoplasmosis cases diagnosed in the country. OBJECTIVE: The aim of this work was to analyze the data collected from 1992 to 2008. Materials and methods. The survey included demographic data, risk factors, clinical manifestations, imaging data, diagnostic methods and antifungal treatment. Patients were grouped according to risk factors and comparisons of the various findings were done. RESULTS: A total of 434 surveys were gathered from 20 of the country's Departments. Most patients (96.1%) were adults, 77% were males with a mean age of 38.4 years. Only 3.9% were children less than 15 years of age. In the adult population, AIDS was reported in 70.5% of the cases; additionally, in 7.0% patients other immunosuppressive conditions were informed. The most frequent clinical manifestations were fever (76.1%), cough (54.8%) and constitutional symptoms (56.8%). X rays abnormalities were represented mainly by infiltrates (65.9%) and nodules (17.1%). Diagnosis was made by microscopic observation of H. capsulatum in 49.6% patients, by culture in 58.0% and by serological test in 14.6% cases. Antifungal use was recorded in 52.5% cases. CONCLUSIONS: Histoplasmosis is frequent in Colombia, especially in certain risk factor groups such as the HIV-infected population. Data collected from this large number of cases has allowed valid comparisons on various aspects of histoplasmosis in Colombia. PMID- 22674313 TI - [Morphological changes in lung tissue of victims associated with the 2009 A H1N1/v09 influenza pandemic in Colombia]. AB - INTRODUCTION: Influenza is an acute respiratory infection that may be seasonal or pandemic. In 2009 The World Health Organization (WHO) declared an influenza pandemia; 3,876 cases and 239 deaths were reported in Colombia. OBJECTIVE: The morphological changes in lung tissues associated with virus infection H1N1/v09 were described from autopsied victims. Materials and methods. Seventy-five cases were diagnosed by RT-PCR for influenza A H1N1/v09, of which the lungs of 20 were selected for morphological study by light microscopy, optical microscopy, high resolution transmission electron microscopy and immunohistochemistry. RESULTS: Of the 75 cases, 83% had viral pneumonitis and 17% alveolitis. Complications included intra-alveolar hemorrhage (66%), edema (89%), diffuse alveolar damage (2%), and bacterial co-infection (32%). Morphological changes were as follows: destruction of the alveolar epithelium and interstitium, edema, macrophages with vacuolated cytoplasm,and infiltration of polymorphonuclear leukocytes in the alveolar lumen and interstitium, vacuolization cytoplasmic type I pneumocytes and electronedense bodies in cellular debris in the alveolar lumen, and immunoreactivity of viral antigens in bronchiolar epithelial cells and alveolar infiltrate. CONCLUSION: The low percentage of bacterial co-infection observed in these cases was a prominent feature, and suggested that the fatal result was probably not associated with secondary bacterial disease (Indicated by previous reports). The tissue lesions were attributed to tissue damage due to viral lesion, as well as the cellular and humoral inflammatory response associated with infiltration by polymorphonucleocytes and macrophages in the interstitium and alveolar lumen. PMID- 22674315 TI - [Intravenous rehydration for diarrheal dehydration of eutrophic children: survey of protocols provided at Colombian medical schools]. AB - INTRODUCTION: In all cases of severe dehydration from diarrhea, WHO recommends rapid rehydration. If oral rehydration in children is contraindicated, intravenous rehydration is recommended for immediate administration. However, methods of intravenous rehydration appear to be inadequately addressed in the medical schools of Colombia. OBJECTIVE: Current approaches to oral rehydration were summarized, and instructors were informed concerning current WHO recommendations. MATERIALS AND METHODS: A survey was designed for pediatric instructors in Colombian medical schools. Direct questions about rehydration methods were included as well as presentation of theoretical clinical situations with dehydrated children. The survey also asked for the conditions necessary for intravenous rehydration and method of administration (volume, solution, concentration and speed of infusion). RESULTS: Forty-one surveys were included (82% of medical schools in Colombia). Inadequate contraindications for oral rehydration therapy were made in 41%. Rapid and slow intravenous rehydration was recommended in 71% and 29%, respectively; 57% recommended fluid bolus to rehydrate. Adequate volumes were recommended by less than half of the respondents and adequate sodium concentration was recommended by 85%. In 56% of medical schools, glucose was not included in solutions and 66% use Ringer lactate. Normal saline solution, dextrose solution with electrolytes and polyelectrolytes solutions are also used. CONCLUSIONS: Misconceptions are common concerning the contraindications to oral rehydration therapy. One-third of medical schools promote a slow therapy despite the superiority of the rapid therapy. Uniformity for rapid therapy schemes is lacking. Bolus rehydration is commonly advocated despite the fact that this method is unsupported by the literature. Concepts about rehydration must be updated in medical schools and a national guide for intravenous rehydration is recommended. PMID- 22674314 TI - Family history and socioeconomic risk factors for non-syndromic cleft lip and palate: a matched case-control study in a less developed country. AB - INTRODUCTION: From an epidemiological point of view, non-syndromic orofacial clefts are the most common oral congenital deformities worldwide. OBJECTIVE: Family histories were traced and socioeconomic risk factors were identified for non-syndromic cleft lip with or without cleft palate. MATERIAL AND METHODS: A case-control study was carried out with 208 cases of non-syndromic cleft lip with or without cleft palate, and matched by age and sex with 416 controls. Cases were patients attending a referral clinic from 2002 through 2004 in Campeche, Mexico. A questionnaire was administered to collect sociodemographic and socioeconomic variables as well as familial background relevant to non-syndromic cleft lip with or without cleft palate. Conditional logistic regression models were used; adjusted odds ratios and 95% confidence intervals were calculated. RESULTS: In the multivariate model, the following risk factors were identified: 1) low socioeconomic status; 2) birth in the southern region of Campeche state; 3) home delivery or delivery in a publicly funded hospital; 4) occurrence of prior non syndromic cleft lip with or without cleft palate cases in the father's or mother's family: 5) having a sibling with non-syndromic cleft lip with or without cleft palate; 6) the proband having another malformation, and 7) a history of infections during pregnancy. Prenatal care consisting of vitamin supplementation was a protective factor for non-syndromic cleft lip with or without cleft palate (odds ratio=0.29). CONCLUSIONS: A "social gradient in health" was seen to link oral malformation with diet components, and several socioeconomic and socio demographic factors broadly encompassed in low socioeconomic status. Further characterization of risk factors will guide the assemblage of a pro-active counseling and prevention program for families at risk for non-syndromic cleft lip and cleft palate. PMID- 22674316 TI - [Reliability and agreement of two smear reading scales for classification and monitoring of multidrug therapy in leprosy patients]. AB - INTRODUCTION: After the clinical diagnosis of leprosy, classification methods are necessary to define a treatment and prognosis of patients consistent with bacterial load. Bacteria are detected in skin smear, and bacterial load typically is established by the internationally used Ridley's logarithmic scale, However, in Colombia an alternative semiquantitative scale is used. OBJECTIVE: The interobserver reproducibility was established for the Ridley and Colombia scales, and the level of correlation-matching was identified between the bacillary indices obtained in order to assess the degree of interchangeability. MATERIALS AND METHODS: Standardization was attained by a reading of the smears by 2 readers with subsequent, blinded evaluation of inter-observer agreement. Each reader quantified the bacterial load of for each sample (n=325) using the Colombian and the Ridley scales. The degree of interobserver agreement was assessed with weighted kappa coefficient. The level of correlation and agreement between the measurements of the bacillary index was established with coefficient of Lin. RESULTS: The interobserver weighted kappa coefficient was 0.83 for the Colombia scale and 0.85 for the Ridley scale. The Lin coefficient was 0.96 for the correlation-matching of bacillary indexes. CONCLUSIONS: Interobserver agreement obtained for both scales was excellent as the correlation-matching bacillary indices determined with both methods. With the cut-off points yielded a good level of agreement, ensuring interchangeability between the scales defining the high or low bacterial load. PMID- 22674317 TI - [Validation by Rasch analysis of the Mania Scale (EMUN) for measuring manic symptions]. AB - INTRODUCTION: The Mania Scale (EMUN) developed at the Universidad Nacional de Colombia was designed to measure the severity of manic symptoms, but has been validated only using classical psychometric theory. OBJECTIVES: The psychometric properties and measuring characteristics of the EMUN scale were determined using an analysis based on item response theory. MATERIALS AND METHODS: Two hundred sixty-four patients with manic, hypomanic or mixed episode symptoms were assessed using the EMUN scale. The psychometric characteristics of the scale were analyzed using a Rasch model for partial credit scoring. RESULTS: The analysis based on the item response theory showed that reliability and separation indexes for persons are low in contrast to items. This suggested a narrow representation of the construct evaluated in this sample. Reduced need to sleep has been the most easily detectable symptom in mania. Excepting depressive affect and distractibility, the majority of items fit the model's expectation The rating scale diagnostics showed that the average measures increase monotonically across the rating scale. Two items showed redundancy and can be omitted in future versions of the scale. The person-item map suggested that the syndrome is not fully evaluated by the scale, probably because some depressive symptoms are not included. CONCLUSION: In this first study to use Rasch analysis to assess the psychometric properties of the EMUN scale, misfit and redundancy of items have been detected. The manic syndrome is not fully evaluated by the scale. The instrument can be improved by adding depressive symptoms. PMID- 22674318 TI - [Determination of the resistance to organophosphate, carbamate, and pyrethroid insecticides in Panamanian Anopheles albimanus (Diptera: Culicidae) mosquitoes]. AB - INTRODUCTION: The susceptibility of Anopheles albimanus to organophosphates, carbamates and pyrethroid insecticides was unknown in the Panama communities of Aguas Claras, Pintupo and Puente Bayano, located in the Amerindian Reservation of Madungandi. This region is considered a malaria transmission area, where An. albimanus is the main vector. OBJECTIVE: The resistance to organophosphate insecticides, carbamates and pyrethroids was evaluated in field populations of the Anopheles albimanus in Panama. MATERIALS AND METHODS: Progeny of An. albimanus collected in three localities in the indigenous Madugandi region were exposed to bioassays of susceptibility to organophosphate insecticides (fenitrothion, malathion and chlorpyrifos), the carbamate (propoxur) and pyrethroids (deltamethrin, lambdacyhalothrin, cyfluthrin and cypermethrin). The protocols were in accordance with those established for adult mosquitoes by World Health Organization. RESULTS: The three strains of the An. albimanus were resistant to the pyrethroid insecticides deltamethrin, lambdacyhalothrin, cyfluthrin and cypermethrin. Susceptibility remained for the organophosphate insecticides fenitrothion, malathion, chlorpyrifos, and the carbamate insecticide propoxur. CONCLUSION: The results provided important information to the vector control program, contributing to the application of new strategies on the use of insecticides, and thereby lengthening the life of the insecticide in use. PMID- 22674319 TI - [Presence of Listeria monocytogenes in ready-to-eat foods available in open markets, delicatessens and supermarkets, Bogota, 2002-2008]. AB - INTRODUCTION: The increase in diseases transmitted by foods has become a public health problem. Listeria monocytogenes, the etiological agent of listeriosis or typical food poisoning,is considered to be among the most important food borne illnesses. High risk foods for L.monocytogenes have been recognized as foods already prepared for consumption and made available in retail outlets. OBJECTIVE: The presence of L. monocytogenes was identified in prepared foods found in open markets and delicatessens in the city of Bogota. MATERIAL AND METHODS: A transverse descriptive study over a 7-year period, with an analytic component, in which 600 foods were analyzed--300 from delicatessens and 300 from open market places. Reference methods were used to determine the presence or absence of L. monocytogenes in 25 grams or milliliters a food sample. RESULTS: Of the 600 samples, 68 were positive for L. monocytogenes (11.3%). Twenty-six (38.2%) were taken from delicatessens and 42 (61.8%) from open market places. The serotype most frequently isolated was 4b, with 53 (78.0%) isolations. Fresh cheeses and matured cheeses showed greater contamination with L. monocytogenes than the other foods (p<0.001 in both cases). CONCLUSIONS: The results indicate that prepared foods are vehicles for the transmission of the Listeria bacterium. These potentially high risk foods are candidates for control and monitoring by public health authorities. Programs must be instituted to implement surveillance norms that lead to the reduction and control of this microorganism and geared toward the prevention of food borne diseases. PMID- 22674320 TI - [Make your own diagnosis: part II]. PMID- 22674321 TI - [Protocol for the combination of neurohistological techniques on vibratome obtained sections]. AB - INTRODUCTION: The histological study of the nervous system requires the use of special techniques. Currently, no methods are available to visualize simultaneously all the cellular constituents of nervous tissue. OBJECTIVES: A protocol was adapted for staining nervous tissue by modification of a formerly difficult procedure. MATERIALS AND METHODS: Slices of brain and spinal cord, 4 mm thick, were taken from adult mice, previously fixed by intracardiac perfusion with 4% paraformaldehyde. Vibratome sections were obtained with thickness of 15 25 um. These were mounted on glass slides prepared with gelatin as an adhesive. The preparations were subjected to staining protocol Luxol Fast Blue-PAS hematoxylin (LPH) combined with silver staining method (LPH-Holmes). RESULTS: LPH technique yielded an excellent differentiation of gray and white matter in all regions of the nervous system. A panoramic view of the gray matter was colored pink in contrast to the myelinated nerve fibers and tracts which were light blue. The combination LPH-Holmes retained the staining characteristics but significantly improved the demarcation of axons and tracts. CONCLUSIONS: A protocol was standardized for the LPH and LPH-Holmes nervous tissue stains applied in combination to tissue slices obtained with a vibratome. The method was shorter, less wasteful and less expensive than the original and also better preserved the integrity of nervous tissue. PMID- 22674322 TI - [Hantavirus as important emerging agents in South America]. AB - The dawning of the 20th century was marked by the emergence of new infectious disease agents and the appearance of others previously thought controlled. Both phenomena were possibly connected with ecological disturbances that led to the recognition of a dramatic climate change, of which the effects are only now becoming noticeable. Among the variety of agents to be considered, the many new viruses stand out, not only for their numerical proliferation, but also for their genetic versatility. It is this quality that provides them dexterity for evolving new strategies and adaptations to changing environmental conditions. Recently, some of the most ubiquitous and well-publicized viral agents in the American continents have been the rodent-borne viruses, and among these are the hantaviruses, etiological agents of pulmonary syndromes. Approximately 18 hantaviruses (belonging to the family Bunyaviridae), have been discovered in South America during the last 20 years, and although most of them cause persistent infections and subclinical infections in wild rodents (particularly members of the subfamily Sigmodontinae) and humans respectively; some others might also be highly lethal for humans. The goal herein is to review the state of the art regarding general aspects of hantaviruses and the diseases they cause around the world, highlighting the most recent findings in Colombia. Finally, the many unanswered questions will be recognized and highlighted concerning clinical importance and socio-economic impact of these agents on quality of public health in Colombia. PMID- 22674323 TI - Decreased arthritis severity in cathepsin L-deficient mice is attributed to an impaired T helper cell compartment. AB - OBJECTIVE: Cathepsin L (CL) is potentially involved in joint destruction and in antigen presentation in rheumatoid arthritis. In order to define the roles of this protease in arthritis development we analysed the antigen-induced arthritis (AIA) in CL-deficient (CL(-/-)) mice. METHODS: Antigen-induced arthritis was induced in CL(-/-) and wild-type mice. Complete CL deficiency resulted in an impaired positive selection of conventional CD4(+) T helper (Th) cells and finally in a reduced number of Th cells. Thus, we addressed the effect of this phenotype by rescuing CD4(+) Th cell numbers by transgenic expression of the human CL-like protease cathepsin V (hCV) in thymic epithelium of CL(-/-) mice [Tg(K14-hCV);CL(-/-)]. The arthritis development was monitored by measuring joint swelling. Joint inflammation and destruction were assessed histopathologically. RESULTS: The severity of AIA was decreased in CL(-/-) mice characterized by reduced swelling, decreased inflammation and destruction, and diminished cellular and humoral immune responsiveness. AIA in Tg(K14-hCV);CL(-/-) mice was associated with a reconstitution of all parameters by normalization of the ratio of regulatory to conventional T cells. CONCLUSIONS: Cathepsin L has a significant impact on AIA severity by influencing the selection of Th cell populations in the thymus, but seems not play any significant role in the direct joint destruction. PMID- 22674325 TI - Is it time for a metagenomic basis of therapeutics? AB - The trillions of microbes associated with the human body are a key part of a comprehensive view of pharmacology. A mechanistic understanding of how the gut microbiota directly and indirectly affects drug metabolism is beginning to emerge. PMID- 22674324 TI - Increase of novel biomarkers for oxidative stress in patients with plasma cell disorders and in multiple myeloma patients with bone lesions. AB - OBJECTIVES: Protein oxidation plays a key role in the pathogenesis of oncological diseases. In this study, we analyzed the oxidative stress in untreated multiple myeloma (MM) patients and in patients affected by monoclonal gammopathy of uncertain significance (MGUS). METHODS: We evaluated serum levels of advanced oxidation protein products (AOPPs), advanced glycation end products (AGEs), and protein nitrosylation in patients with monoclonal gammopathy and in control subjects. RESULTS: Serum levels of AOPPs and S-nitrosylated proteins were significantly increased in MM patients in comparison to controls and to MGUS subjects. Moreover, in MM patients the levels of AOPPs, AGEs and S-nitrosylated proteins were significantly higher in patients with bone lesions compared with those without lytic bone lesions. CONCLUSIONS: MM is closely associated with oxidative stress and further investigation might provide an insight to understand a putative causal link between oxidative stress and MM disease onset and progression or MM complications. PMID- 22674326 TI - Honor thy gut symbionts redux. AB - Exploring our gut microbial communities with new tools is allowing us to revisit old questions; to develop new concepts about our evolution, postnatal development, systems physiology, individuality, and definitions of health; and to further delineate the impact of our changing life-styles. It is also allowing us to envision exciting new ways for addressing global health problems. This area is inherently interdisciplinary, offering a wealth of opportunities to create new fields, partnerships, and educational initiatives. It is captivating to the public and carries substantial expectations. As such, participating scientists need to sponsor proactive, solution-focused discussions of its societal implications. PMID- 22674327 TI - My microbiome and me. PMID- 22674328 TI - Interactions between commensal fungi and the C-type lectin receptor Dectin-1 influence colitis. AB - The intestinal microflora, typically equated with bacteria, influences diseases such as obesity and inflammatory bowel disease. Here, we show that the mammalian gut contains a rich fungal community that interacts with the immune system through the innate immune receptor Dectin-1. Mice lacking Dectin-1 exhibited increased susceptibility to chemically induced colitis, which was the result of altered responses to indigenous fungi. In humans, we identified a polymorphism in the gene for Dectin-1 (CLEC7A) that is strongly linked to a severe form of ulcerative colitis. Together, our findings reveal a eukaryotic fungal community in the gut (the "mycobiome") that coexists with bacteria and substantially expands the repertoire of organisms interacting with the intestinal immune system to influence health and disease. PMID- 22674329 TI - Tackling the microbiome. PMID- 22674330 TI - Host-gut microbiota metabolic interactions. AB - The composition and activity of the gut microbiota codevelop with the host from birth and is subject to a complex interplay that depends on the host genome, nutrition, and life-style. The gut microbiota is involved in the regulation of multiple host metabolic pathways, giving rise to interactive host-microbiota metabolic, signaling, and immune-inflammatory axes that physiologically connect the gut, liver, muscle, and brain. A deeper understanding of these axes is a prerequisite for optimizing therapeutic strategies to manipulate the gut microbiota to combat disease and improve health. PMID- 22674332 TI - Pigs as stand-ins for microbiome studies. PMID- 22674331 TI - Innate lymphoid cells promote anatomical containment of lymphoid-resident commensal bacteria. AB - The mammalian intestinal tract is colonized by trillions of beneficial commensal bacteria that are anatomically restricted to specific niches. However, the mechanisms that regulate anatomical containment remain unclear. Here, we show that interleukin-22 (IL-22)-producing innate lymphoid cells (ILCs) are present in intestinal tissues of healthy mammals. Depletion of ILCs resulted in peripheral dissemination of commensal bacteria and systemic inflammation, which was prevented by administration of IL-22. Disseminating bacteria were identified as Alcaligenes species originating from host lymphoid tissues. Alcaligenes was sufficient to promote systemic inflammation after ILC depletion in mice, and Alcaligenes-specific systemic immune responses were associated with Crohn's disease and progressive hepatitis C virus infection in patients. Collectively, these data indicate that ILCs regulate selective containment of lymphoid-resident bacteria to prevent systemic inflammation associated with chronic diseases. PMID- 22674333 TI - Taking stock of the human microbiome and disease. PMID- 22674336 TI - The gut microbiota. Introduction. PMID- 22674334 TI - Interactions between the microbiota and the immune system. AB - The large numbers of microorganisms that inhabit mammalian body surfaces have a highly coevolved relationship with the immune system. Although many of these microbes carry out functions that are critical for host physiology, they nevertheless pose the threat of breach with ensuing pathologies. The mammalian immune system plays an essential role in maintaining homeostasis with resident microbial communities, thus ensuring that the mutualistic nature of the host microbial relationship is maintained. At the same time, resident bacteria profoundly shape mammalian immunity. Here, we review advances in our understanding of the interactions between resident microbes and the immune system and the implications of these findings for human health. PMID- 22674335 TI - The application of ecological theory toward an understanding of the human microbiome. AB - The human-microbial ecosystem plays a variety of important roles in human health and disease. Each person can be viewed as an island-like "patch" of habitat occupied by microbial assemblages formed by the fundamental processes of community ecology: dispersal, local diversification, environmental selection, and ecological drift. Community assembly theory, and metacommunity theory in particular, provides a framework for understanding the ecological dynamics of the human microbiome, such as compositional variability within and between hosts. We explore three core scenarios of human microbiome assembly: development in infants, representing assembly in previously unoccupied habitats; recovery from antibiotics, representing assembly after disturbance; and invasion by pathogens, representing assembly in the context of invasive species. Judicious application of ecological theory may lead to improved strategies for restoring and maintaining the microbiota and the crucial health-associated ecosystem services that it provides. PMID- 22674338 TI - Serious adverse events-missing in action: comment on the article by Kremer et al. PMID- 22674337 TI - The association between post-traumatic stress disorder symptoms and the quality of life among Wenchuan earthquake survivors: the role of social support as a moderator. AB - OBJECTIVE: To examine the role of the three types of social support as possible moderating factors between post-traumatic stress disorder (PTSD) and its relationship to two domains of the quality of life (QOL). METHODS: A cross sectional survey was done in a local area near the epicenter of the severe earthquake in Wenchuan. The Diagnostic and statistical manual of mental disorders, fourth edition (DSM-IV), the standard Chinese 12-item Short Form (SF 12v2), and the Social Support Rating Scale (SSRS) were used to interview a total of 2,080 earthquake survivors in the one-year follow-up period. Multiple regressions were performed to evaluate the moderating role of social support on the relationship between PTSD and QOL. RESULTS: Among survivors one-year after the Wenchuan earthquake, being a woman (p < 0.01), having a lower level of education (p < 0.01), having a lower level of income (p < 0.01), having a worse housing status (p < 0.05) and having a higher level of exposure (p < 0.05) were risk factors for a poorer QOL (?R (2) = 0.063). PTSD symptoms negatively influenced the QOL (?R (2) = 0.145), while social support positively influenced the QOL (?R (2) = 0.016). However, the interaction between social support and PTSD weakened the negative effect of PTSD on the QOL (?R (2) = 0.012). Subjective support and support availability moderated the association between PTSD and the QOL (?R (2) = 0.010). CONCLUSION: Subjective support and support availability are more useful strategies to improve the QOL of the earthquake survivors with PTSD symptoms. PMID- 22674339 TI - Benign fibrous dysplasia on [(11)C]choline PET: a potential mimicker of disease in patients with biochemical recurrence of prostate cancer. AB - We present the case of a 74-year-old male with biochemical recurrence of prostate cancer who underwent [(11)C]choline PET/CT. The PET/CT demonstrated an intense focus of uptake within the skull base that was initially felt to potentially represent metastatic disease. Subsequent evaluation with MRI and dedicated thin section CT revealed this area to be benign fibrous dysplasia of the bone. The focal uptake on PET/CT with [(11)C]choline in benign fibrous dysplasia represents a potential mimicker of metastatic disease. Due to recognizing this benign process, our patient was able to avoid systemic treatment and/or focal radiation and was treated with cryotherapy for biopsy-proven local recurrence within the prostate bed. While benign fibrous dysplasia can demonstrate increased radiotracer uptake on other modalities (i.e., bone scintigraphy, FDG PET/CT), its appearance on [(11)C]choline PET/CT has been largely overlooked in the literature. With the increasing use of [(11)C]choline PET/CT for biochemical recurrent prostate cancer evaluation, it is important to understand this potential mimicker of disease. PMID- 22674340 TI - Antibodies that cross-neutralize the tier-2 pseudoviruses are produced in antiretroviral-naive HIV-1-infected children from northern India. AB - In this cross-sectional study, we evaluated the efficiency of the plasma of 38 antiretroviral-naive HIV-1-infected children from northern India against a standard panel of pseudoviruses (3 clade C and 3 clade B) by TZM-bl assay. Neutralization potential was observed to a variable extent, with a potency ranging up to reciprocal ID(50) titers of 1967. Cross-neutralization was observed in 28.9 % (11/38) of the children. There was a significant positive correlation between viremia and neutralization efficiency against two of the viruses studied (Du172 r = 0.49; p = 0.007 and RHPA r = 0.47; p = 0.01), suggesting that persistent antigenic stimulation is necessary for the generation of broadly neutralizing antibody responses in these children. Further mapping of the epitope specificities of the neutralization determinants in the polyclonal plasma would provide important information for immunogen design. PMID- 22674341 TI - Vaccinia virus infection suppresses the cell microRNA machinery. AB - MicroRNAs are key players in the regulation of gene expression by posttranscriptional suppression. They are involved in physiological processes, and thus their deregulation may contribute to the development of diseases and progression of cancer. Virus-encoded microRNAs and microRNAs of host origin play an important role in controlling the virus life cycle and immunity. The aim of this study was to determine the effect of vaccinia virus (VACV) infection on the expression of host-encoded microRNAs. A marked general suppression of most microRNAs in the infected cells was observed within 24 hours after VACV infection of a number of cell types. We demonstrate that this suppression was associated with abrogation of expression of the Dicer1 enzyme, which is a key enzyme in the generation of microRNAs. PMID- 22674342 TI - Salt effect on phenolics and antioxidant activities of Tunisian and Canadian sweet marjoram (Origanum majorana L.) shoots. AB - BACKGROUND: Two varieties of Origanum majorana (Canadian and Tunisian) were evaluated for their phenolic, flavonoid and tannin contents, individual phenolic compounds and antioxidant activities under NaCl constraint. RESULTS: The results showed a significant variability in phenolic composition and antioxidant behavior between the two varieties under salt stress. The phenolic composition of methanolic extracts was determined by reversed-phase high-performance liquid chromatography. Amentoflavone was the predominant flavonoid compound; in addition, trans-2-hydrocinnamic acid became the major phenolic acid with salt treatment of the Tunisian variety. In the control, Canadian variety extract was characterized by high levels of gallic acid and amentoflavone. However, under 75 mmol L(-1) NaCl, gallic acid content doubled, whereas amentoflavone content was maintained in the Canadian variety. Stimulation of phenolic acid biosynthesis was observed in these two varieties under salt treatment despite the fact that shoots of the Tunisian variety showed higher antioxidant activities compared to those from the Canadian variety. Tunisian O. majorana might have developed tolerance to salinity and avoided tissue damage by activating enzymes involved in the galactosylation of quercetin into quercetin-3-galactoside and quercetin-3 rhamnoside. CONCLUSION: Our results confirmed the tolerance of Tunisian O. majorana plants. PMID- 22674344 TI - Dermoid cyst of the pancreas. PMID- 22674345 TI - Safety and efficacy of colorectal endoscopic submucosal dissection in elders: clinical and follow-up outcomes. AB - PURPOSE: Endoscopic submucosal dissection (ESD) has recently been applied to treatment of colorectal neoplasia; however, its safety and efficacy in terms of follow-up outcomes in elders have not been thoroughly examined. The aim of this study is to describe the clinical outcomes of colorectal ESD in elderly patients. METHODS: Two groups of patients, elderly (>= 75 years of age) and non-elderly (< 75 years of age), who underwent colorectal ESD at the National Cancer Center Hospital from February 1998 to December 2010 were retrospectively compared on the following measures: tumor size, procedure time, complication rates, en bloc resection rates, and curative resection rates. We also investigated the follow-up outcomes in non-curative resection cases. RESULTS: Of 614 consecutive patients treated by colorectal ESD, 125 (20.4 %) comprised the elderly group, and 489 patients (79.6 %) comprised the non-elderly group. No significant differences were observed between the two groups in terms of tumor size, procedure time, complication rates, en bloc resection rates, and curative resection rates. Of the patients who underwent non-curative resection, 7/19 (36.8 %) and 47/63 (74.6 %) in the elderly and non-elderly group, respectively, underwent additional treatment. Among the elderly patients who were followed up without additional treatment, no case of local recurrence, residual lesions, or distant metastases was observed during the observation period. CONCLUSION: Treatment outcomes of colorectal ESD were equivalent in both groups. However, many of the non-curative cases in the elderly patients were followed up without additional treatment. Future studies should focus on the outcome in such patients to confirm the feasibility of colorectal ESD in elderly patients. PMID- 22674346 TI - Primary cancers before and after prostate cancer diagnosis. AB - BACKGROUND: The occurrence of multiple cancers may indicate common etiology; and, although some studies have investigated the risk of second primary cancers after prostate cancer (PCa), there are no studies on cancers before PCa. METHODS: The PCBaSe Sweden database is based on the National Prostate Cancer Register (NPCR), which covers >96% of PCa cases. The authors estimated the prevalence and cumulative incidence of different cancers before and after PCa diagnosis in 72,613 men according to PCa treatment and disease stage in PCBaSe and their matched comparison cohort of men who were free of PCa. RESULTS: In total, 6829 men were diagnosed with another primary cancer before their PCa diagnosis, including 138 men at the time of PCa diagnosis and 5230 men were diagnosed after PCa diagnosis. Cancer of the bladder or colon and nonmelanoma of the skin were the 3 most frequently observed cancers before and after PCa diagnosis. At the time of PCa diagnosis, the prevalence of these 3 cancers was 1.94% for bladder cancer, 1.08% for colon cancer, and 1.08% for nonmelanoma skin cancer, compared with 1.30%, 0.96%, and 1.03%, respectively, for the matched comparison cohort. Five years after PCa diagnosis, the difference in incidence proportion between PCa men and their comparison cohort was 7 0/00 (95% CI, 5.6 0/00-8.5 0/00), 1.3 0/00 (0 0/00-2.6 0/00), and 1.6 0/00 (0.6 0/00-2.6 0/00) for these 3 cancers, respectively. From a uro-oncologic point of view, it is interesting to note that the prevalence of kidney cancer at the time of PCa diagnosis was 0.42% compared with 0.28% for the matched comparison cohort. CONCLUSIONS: Approximately 17% of all PCa occurred in combination with another primary cancer (before or after PCa diagnosis). Detection bias probably explains part of this observation, but further investigations are required to assess possible underlying mechanisms. PMID- 22674348 TI - Involvement of endoplasmic reticulum stress in optic nerve degeneration following N-methyl-D-aspartate-induced retinal damage in mice. AB - We evaluated time-dependent optic nerve degeneration and the role of endoplasmic reticulum (ER) stress in this process following retinal ganglion cell death in mice. Retinal damage was induced by intravitreal injection of N-methyl-D aspartate (NMDA). Neurofilament heavy (NFH)- and phosphorylated NFH (pNFH) positive axons were time-dependently decreased in optic nerves at 1, 3, 7, 14, and 28 days after NMDA injection. Expression of glial fibrillary acidic protein (GFAP)-positive astroglial cells and ionized calcium-binding adaptor molecule 1 (Iba1)-positive microglial cells showed a significant increase in the optic nerve at 7, 14, and 28 days after NMDA injection. In contrast, expression of myelin basic protein (MBP)-positive oligodendrocytes showed a significant decrease in the optic nerve at 7, 14, and 28 days after NMDA injection. In quantitative RT PCR analysis, expressions of glucose-regulated protein 78 (Grp78)/BiP, Grp94, Calreticulin, C/EBP homologous protein (Chop), and the ER degradation enhancer mannosidase alpha-like 1 (Edem1) genes were increased in the optic nerve at 14 days after NMDA injection. In addition, the Grp94 gene was increased at 7 days after NMDA injection, and the Edem1 gene was increased at 3, 7, and 28 days after NMDA injection. GRP78 and CHOP proteins were colocalized with MBP in the optic nerve after NMDA injection. These findings suggest that the axonal degeneration is dramatic until 7 days after NMDA injection and that glial cells may play some role in the degeneration of the optic nerve. Furthermore, ER stress may play a pivotal role in the decrease of MBP-positive oligodendrocytes after NMDA-induced retinal damage. PMID- 22674347 TI - Characteristics of persons with overactive bladder of presumed neurologic origin: results from the Boston Area Community Health (BACH) survey. AB - AIMS: To compare the descriptive epidemiology of overactive bladder (OAB) of presumed neurologic origin (NOAB) to OAB of non-neurologic origin (N-NOAB). METHODS: Five thousand five hundred three community-dwelling persons aged 30-79 were interviewed regarding urologic symptoms (2002-2005). NOAB was defined as symptoms of urgency and/or urgency incontinence among those with a self-reported history of healthcare provider diagnosed stroke (N = 98), multiple sclerosis (N = 21), or Parkinson's disease (N = 7). N-NOAB was defined identically but occurring among those not reporting neurologic disease (ND). Prevalence estimates were weighted to reflect sampling design; chi-square, Fisher's exact, or t-tests were used to test differences. Urologic symptom interference was assessed using the Epstein scale, while the impact of urinary incontinence (UI) on health-related quality-of-life (HRQOL) was measured using a modification of the Incontinence Impact Questionnaire-7. RESULTS: Forty-five (31.0%) of 125 persons with ND and 994 (16.7%) of 5378 persons without ND reported OAB symptoms. The overall prevalence of NOAB and N-NOAB was 0.6% and 16.4%, respectively. Persons with NOAB had higher (worse) mean American Urologic Association Symptom Index scores (13.0 vs. 10.0, P = 0.09) compared to those with N-NOAB, and were significantly more likely to have diabetes, high blood pressure, cardiac disease, and fair/poor self reported health (all P < 0.05). Mean symptom interference and UI HRQOL scores were significantly higher (worse) in the NOAB group compared to persons with N NOAB (all P < 0.05). CONCLUSIONS: Persons with NOAB appeared to have a greater burden of urologic illness with respect to symptom interference and HRQOL compared to persons with N-NOAB. PMID- 22674349 TI - Butyric acid: what is the future for this old substance? AB - In this brief review, we present some data from the literature on butyric acid and some of its more interesting potential uses, especially in the field of gastroenterology. Due to its principal characteristics, butyric acid is primarily used for pathologies of the colon (functional, inflammatory). Although only preliminary data are available, butyric acid may also have interesting extraintestinal applications, such as in the treatment of haematological, metabolic, and neurological pathologies. PMID- 22674350 TI - Use of general anesthesia and sentinel node procedure during pregnancy. PMID- 22674351 TI - Activation of Wnt Planar Cell Polarity (PCP) signaling promotes growth plate column formation in vitro. AB - Disrupting the Wnt Planar Cell Polarity (PCP) signaling pathway in vivo results in loss of columnar growth plate architecture, but it is unknown whether activation of this pathway in vitro is sufficient to promote column formation. We hypothesized that activation of the Wnt PCP pathway in growth plate chondrocyte cell pellets would promote columnar organization in these cells that are normally oriented randomly in culture. Rat growth plate chondrocytes were transfected with plasmids encoding the Fzd7 cell-surface Wnt receptor, a Fzd7 deletion mutant lacking the Wnt-binding domain, or Wnt receptor-associated proteins Ror2 or Vangl2, and then cultured as three-dimensional cell pellets in the presence of recombinant Wnt5a or Wnt5b for 21 days. Cellular morphology was evaluated using histomorphometric measurements. Activation of Wnt PCP signaling components promoted the initiation of columnar morphogenesis in the chondrocyte pellet culture model, as measured by histomorphometric analysis of the column index (ANOVA p = 0.01). Activation of noncanonical Wnt signaling through overexpression of both the cell-surface Wnt receptor Fzd7 and receptor-associated protein Ror2 with addition of recombinant Wnt5a promotes the initiation of columnar architecture of growth plate chondrocytes in vitro, representing an important step toward growth plate regeneration. PMID- 22674353 TI - Sequential therapy in metastatic renal cell carcinoma: pre-clinical and clinical rationale for selecting a second- or subsequent-line therapy with a different mechanism of action. AB - Few types of cancer have had their treatment evolve as rapidly as metastatic renal cell carcinoma (mRCC). Since 2005, six new targeted therapies with proven efficacy have been approved for the treatment of mRCC. The downside is that our knowledge about the mechanisms of action of these therapies and the intrinsic and extrinsic mechanism of resistance has not evolved equally fast, and many questions remain unanswered. The only approved agent to date in the European Union for patients who progress on sunitinib or sorafenib is everolimus. The results of the phase III trial comparing axitinib vs. sorafenib after failure on sunitinib, bevacizumab, temsirolimus, or cytokines have recently been published, and axitinib has recently been licensed by the Food and Drugs Administration. Other phase III trials that are being conducted include a comparison between everolimus plus bevacizumab and everolimus after failure on tyrosine kinase inhibitors, and between temsirolimus and sorafenib after failure on sunitinib. In this article, we will review the available evidence from clinical studies on sequential therapy for mRCC, including those that are still in progress. In addition, information on the mechanism of resistance or tolerance to first-line therapy, recommendations of the main practice guidelines for second-line treatment, potential therapies for third or successive treatment lines, and the major reasons why patients who progress may benefit from a change of mechanism of action will also be discussed. PMID- 22674352 TI - Psychosis in Parkinson's disease without dementia: common and comorbid with other non-motor symptoms. AB - Psychosis in Parkinson's disease (PD) is common and associated with a range of negative outcomes. Dementia and psychosis are highly correlated in PD, but the frequency and correlates of psychosis in patients without cognitive impairment are not well understood. One hundred and ninety-one non-demented PD patients at two movement disorders centers participated in a study of neuropsychiatric complications in PD and completed a detailed neurological and neuropsychiatric assessment, including the rater-administered Parkinson Psychosis Rating Scale for hallucinations, delusions, and minor symptoms of psychosis (illusions and misidentification of persons). Psychotic symptoms were present in 21.5% of the sample. Visual hallucinations were most common (13.6%), followed by auditory hallucinations (6.8%), illusions or misidentification of people (7.3%), and paranoid ideation (4.7%). Visual hallucinations and illusions or misidentification of people were the most common comorbid symptoms (3.1%). Depression (P = 0.01) and rapid eye movement behavior disorder symptoms (P = 0.03) were associated with psychosis in a multivariable model. The odds of experiencing psychotic symptoms were approximately five times higher in patients with comorbid disorders of depression and sleep-wakefulness. Even in patients without global cognitive impairment, psychosis in PD is common and most highly correlated with other non-motor symptoms. Screening for psychosis should occur at all stages of PD as part of a broad non-motor assessment. In addition, these findings suggest a common neural substrate for disturbances of perception, mood, sleep-wakefulness, and incipient cognitive decline in PD. PMID- 22674354 TI - Molecular characterisation of the monocytic cell line THP-1 demonstrates a discrepancy with the documented HLA type. PMID- 22674356 TI - Efficacy and safety of solifenacin to treat overactive bladder symptoms in patients with idiopathic normal pressure hydrocephalus: an open-label, multicenter, prospective study. AB - AIMS: To evaluate the efficacy and safety of solifenacin 5 mg to treat voiding symptoms caused by idiopathic normal pressure hydrocephalus (iNPH) after a ventriculoperitoneal (V-P) shunt operation. METHODS: A total of 53 patients diagnosed with iNPH and complaining of voiding symptoms were enrolled. Before treatment with solifenacin (V1), 4 (V2) and 12 (V3) weeks after starting solifenacin overactive bladder symptom score (OABSS), the International Prostate Symptom Score (IPSS), Quality of Life (QoL) score, maximal urine flow rate (Q(max) ), voided volume, and post-voiding residual urine volume (PVR) were measured. An urodynamic study (UDS) was performed at V1 and V3, and the safety of solifenacin was assessed at V1, V2, and V3. RESULTS: Of the 53 patients, 38 patients (71.70%) completed the 12-week clinical trial. The mean patient age was 52.24 +/- 10.08 years. OABSS and IPSS were significantly improved. The mean voided volume was 147.18 +/- 61.84 ml at V1 and 160.03 +/- 62.59 ml at V3 (P < 0.001), and PVR was 64.87 +/- 41.11 ml at V1 and 69.05 +/- 39.54 ml at V3 (P = 0.009). Of the 31 patients who underwent UDS, 26 patients (83.87%) had detrusor overactivity (DO) at V1, with a mean value of 107.67 +/- 18.13 ml. Of the 26 with DO at V1, 22 (84.62%) still had DO at V3. A mean DO of 131.66 +/- 15.27 ml was observed at V3 (P < 0.001). The most common adverse effects was dry mouths. CONCLUSIONS: Solifenacin is effective in the treatment of OABS in iNPH patients who underwent the V-P shunt operation. Solifenacin increases bladder capacity causing of DO at UDS. PMID- 22674355 TI - Phylogenetic analysis of Ostreococcus virus sequences from the Patagonian Coast. AB - A phylogenetic analysis of new Ostreococcus virus (OV) sequences from the Patagonian Coast, Argentina, and homologous sequences from public databases was performed. This analysis showed that the Patagonian sequences represented a divergent viral clade and that the rest of OV sequences analyzed here were clustered into six additional phylogenetic groups. Analyses of 18S gene libraries supported a close relationship of the Patagonian Ostreococcus host with clade A sequences described elsewhere, corroborating previous studies indicating that clade A strains are ubiquitous. Besides the Patagonian OV sequences, several phylogenetic groupings were linked to particular geographic locations, suggesting a role for allopatric cladogenesis in viral diversification. However, and in agreement with previous observations, other viral lineages included sequences with diverse geographic origins. These findings, together with analyses of ancestral trait trajectories performed here, are consistent with an evolutionary dynamics in which geographical isolation has a role in OV diversification but can be followed by rapid dispersion to remote places. PMID- 22674357 TI - [Cardiovascular diseases: a public health problem and a global challenge]. PMID- 22674358 TI - [Evaluation of the seroconversion as a response to rabies vaccination in dogs, Valle del Cauca, Colombia, 2009]. AB - INTRODUCTION: The province of Valle del Cauca has been free of dog rabies for more than 20 years. However, sylvatic rabies foci remain which are threats to the health of the populace and its pets. Rabies vaccination campaigns are carried out annually in all 42 counties of the province. OBJECTIVES: The impact of dog vaccination was evaluated on the basis of humoral immunoresponse, population parameters and correlation with variables inherent to the vaccination process and logistics. MATERIALS AND METHODS: Sera and associated data were obtained from each of the 42 counties for a total sample of 569 rabies-vaccinated dogs. Rabies neutralizing antibodies were measured by quantitative ELISA. The data were analyzed with the statistical programs in Epi-Info 6.0. RESULTS: Nearly 10% of dogs were seronegative (9.1%) and an additional 25.1% did not elicit an adequate humoral immune response to vaccination. Concentration of rabies neutralizing antibodies diminished gradually with the time after vaccination and was correlated with dog age and vaccine quality. No associations were noted between dog gender or breed. CONCLUSIONS: These data permit the following recommendations: (1) only viable, non expired rabies vaccines must be used to immunize animals, (2) two doses of rabies vaccine must be applied during the first six months of dog life, (3) booster immunizations must be administered every year, (4) practices and processes related to rabies vaccination in private institutions must inspected regularly by health authorities. PMID- 22674359 TI - [Necrotizing enterocolitis among preterm newborns with early feeding]. AB - INTRODUCTION: The development of necrotizing enterocolitis is a common and serious risk to newborns. It is caused by splanchnic bed vasoconstriction that can produce intestinal necrosis. The role of onset time, type and, speed enhancements of The factors of enteral feeding related with necrotizing enterocolitis genesis such as feeding onset, type and frequency are not well understood. OBJECTIVE: The incidence of necrotizing enterocolitis and mortality among infants will be compared in infants whose enteral feeding was initiated 48 hours after birth to those whose feeding began on day 5 postpartum. MATERIALS AND METHODS: A controlled clinical trial was conducted among 239 newborns weighing between 750-1,500 g and a gestation age of 27-32 weeks of gestational age. The infants were randomly assigned to two groups--135 to an early feeding regime and 104 to delayed feeding. Breast milk or formula milk was used. Feeding was begun with one ml every six hours, progressing to three hour intervals and 20 ml/kg daily. This was increased to 150 ml/kg-d if the infant condition remained stable and it manifested no oral intolerance. RESULTS: In the early feeding group, 14 (10;4 %) necrotizing enterocolitis cases occurred, and in the late feeding group, 9 (8.7 %) occurred (RR= 1.22, 95 % CI 0.49-3.20, p= 0.65). Five children died in early feeding group (3.7 %, 95% CI 1.4-8.9) and eight in late feeding group (7.7 %, 95 % CI 3.6-15.0, RR=0.46, 95 % CI 0.12-1,60, p= 0.18). CONCLUSION: Early enteral feeding in preterm newborns does not increase the risk of necrotizing enterocolitis or mortality among them; however it represents nutritional advantages for these infants. PMID- 22674360 TI - [Quality of life in institutionalized elderly people of Medellin]. AB - INTRODUCTION: Many factors contribute to the deteriorating quality of life of elderly people living in care institutions. Some of these problems are a consequence of few contacts with relatives and friends, and being alone with a feeling of isolation. OBJECTIVE: The conditions of quality of life are explored for elderly people living in care institutions. MATERIALS AND METHODS: In a cross sectional study, 276 subjects were selected from 39 long term institutions located in the city of Medellin, Colombia. The sex ratio was female: male 60:40% with a mean age of 79.2 +/- 8.0. Elderly subjects with cognitive problems or not living in the institution were excluded. The World Health Organization Quality of Life of Older Adults (WHOQOL-OLD) questionnaire was applied; in additional, capacity and cognitive functional scales of Pfeffer, the anxiety scale of Goldberg, and the Geriatric Depression Scale of Yesavage were administered. Mininutritional assessment scales and complementary questionnaires about demographics, health perception, social support system were also included. The information was analyzed using the Mann Whitney U test, Kruskal Wallis test, Pearson correlation and multiple linear regression method. RESULTS: Most (71%) considered themselves autonomous for undertaking daily, habitual activities. Other statistics included the following: 45.7% with depression, 33.0% with anxiety, 28.3% with functional problems, and 54.3% at risk of malnutrition. A negative quality-of-life assessment was associated with the following factors: female, diabetes, depression, anxiety and high functional capacity. A positive quality-of-life assessment was associated with individuals who voluntarily came to the institution. CONCLUSION: Quality of life for elderly people living in care institutions can become deteriorated when they are not capable to do the usual activities necessary for daily living. Exacerbating factors included sex, symptoms of depression, anxiety, or perceived mistreatment by their families. PMID- 22674361 TI - [Differential protein expression in developmental stages of Trypanosoma cruzi I isolated from a patient with chronic chagasic cardiomyopathy]. AB - INTRODUCTION: Trypanosoma cruzi is the causative agent of Chagas disease. During infection in mammalian hosts, two main forms of the parasite are observed: trypomastigotes and amastigotes. During differentiation, each stage of the parasite expresses a pattern of proteins specific to each phase-proteins which are responsible for the cell's morphological, biochemical and biological properties. These properties ultimately govern the infectivity, virulence and survival of the parasite. OBJECTIVE: A differential expression analysis was conducted to compare trypomastigote and amastigote stages of T. cruzi I isolate, and to identify proteins differentially expressed by means of mass spectrometry. MATERIALS AND METHODS: A T. cruzi clone of the strain MHOM/07/338 was used to analyze the differential expression between trypomastigote stages of a T. cruzi isolate, using two-dimensional electrophoresis and identification of differentially expressed proteins by mass spectrometry. The protein profiles of the stages of the parasite were obtained by two-dimensional gel electrophoresis and visualized in gels dyed with Coomassie blue. The images were analyzed with PDQuest software and the differential expression of the proteins was identified by MALDI TOF or LC MS/MS. RESULTS: The two-dimensional gels revealed an average of 325 protein spots in each stage. The comparative analyses detected 21 spots that were over expressed in the trypomastigote stage and 30 in the amastigote stage. Sixteen of the over expressed proteins were selected for identification by mass spectrometry and classified in several functional categories. Mass spectrophotometry determined that the proteins were associated mainly with glucolytic metabolism and assembly of the cytoskeleton constituents. CONCLUSIONS: The differential expression between trypomastigote and amastigote stages consisted of proteins specific to T. cruzi and are potential targets for the design of treatment drugs. PMID- 22674362 TI - [Cost-effectiveness of laparoscopic versus open cholecystectomy]. AB - INTRODUCTION: Cholecystectomy has been the subject of several clinical and cost comparison studies. OBJECTIVE: The results of open or laparoscopy cholecystectomy were compared in terms of cost and effectiveness from the perspective of health care institutions and from that of the patients. MATERIALS AND METHODS: The cost effectiveness study was undertaken at two university hospitals in Bogota, Colombia. The approach was to select the type of cholecystectomy retrospectively and then assess the result prospectively. The cost analysis used the combined approach of micro-costs and daily average cost. Patient resource consumption was gathered from the time of surgery room entry to time of discharge. A sample of 376 patients with cholelithiasis/cystitis (May 2005-June 2006) was selected--156 underwent open cholecystectomy and 220 underwent laparoscopic cholecystectomy. The following data were tabulated: (1) frequency of complications and mortality, post-surgical hospital stay, (2) reincorporation to daily activities, (3) surgery duration, (4) direct medical costs, (5) costs to the patient, and (6) mean and incremental cost-effectiveness ratios. RESULTS: Frequency of complications was 13.5% for open cholecystectomy and 6.4% for laparoscopic cholecystectomy (p=0.02); hospital stay was longer in open cholecystectomy than in laparoscopic cholecystectomy (p=0.003) as well as the reincorporation to daily activities reported by the patients (p<0.001). The duration of open cholecystectomy was 22 min longer than laparoscopic cholecystectomy (p<0.001). The average cost of laparoscopic cholecystectomy was lower than open cholecystectomy and laparoscopic cholecystectomy was more cost-effective than open cholecystectomy (US$ 995 vs. US$ 1,048, respectively). The patient out-of-pocket expenses were greater in open cholecystectomy compared to laparoscopic cholecystectomy (p=0.015). Mortality was zero. CONCLUSIONS: The open laparoscopy procedure was associated with longer hospital stays, where as the cholecystectomy procedure required a longer surgical duration. The direct cost of the latter was lower for both for the health care institution and patients. The cost-effectiveness for both procedures was comparable. PMID- 22674363 TI - [Expression of IL-10, IL-4 and IFN-gamma in active skin lesions of children with papular urticaria]. AB - INTRODUCTION: Papular urticaria caused by the bites of fleas traditionally has been defined as a chronic allergic disease. However, currently no clear relationship has been described between this pathology and common allergic diseases. OBJECTIVE: The expression of IL-10, IL-4 and IFN-gamma as markers of effector T cell responses was examined in skin lesions of patients with papular urticaria by flea bite. MATERIALS AND METHODS: Fourteen skin lesion biopsies were sampled from children with a clinical diagnosis of papular urticaria by flea bite and were compared with 5 healthy skin biopsies of children with no history of the disease. All children were under 12 years old. RNA was extracted with trizol and the expression levels of cytokines were analyzed by real time PCR technique. RESULTS: A wide range in the expression levels of IFN-gamma and IL-10 was noted as well as constant low values of IL-4. Three distinct profiles were observed, but which did not correspond to a recognizable pattern among the patients. The samples obtained from healthy tissues showed no expression of any of the cytokines. CONCLUSIONS: This is the first characterization of cytokines that mediate the immune response at the site of the skin lesion in children with papular urticaria by flea bite. The data indicated that the local response was mixed and that a single phenotype is not predominant among the patients. PMID- 22674364 TI - [Health related quality of life in adults with HIV/AIDS in Colombia]. AB - INTRODUCTION: HIV/AIDS is now considered a chronic treatable disease because of the effectiveness of antiretroviral therapy. However, for this disease, issues require evaluation that goes beyond of disease occurrence. Health-related quality of life changes that may occur that continue throughout the life of the patient and may include functional status, perceptions of others, social opportunities, treatment requirements and disability. OBJECTIVE: The health-related quality of life is to be characterized along with its association with demographic, socioeconomic and clinical conditions in adults with HIV/AIDS. MATERIALS AND METHODS: A cross-sectional study was conducted on a sample of 187 people with HIV/AIDS in Medellin, 2009. The Medical Outcome Study Short Form (MOSSF36) and the World Health Organization Quality of Life (WHOQOL-BREF) were applied. The analysis was done with proportions, summary measures, confidence intervals, t Student, U Mann-Whitney, Kruskal-Wallis, ANOVA and multiple linear regressions. RESULTS: In this sample, 83.0% used antiretrovirals, 74.7% had adherence exceeding 95% and 74.7% had CD4 count above 200/mm(3). The scores of health related quality of life were between 60.5 and 90.2. Presence of disease, satisfaction with family support and satisfaction with the economic situation were the conditions found most relevant to the quality of life. CONCLUSION: In adults with HIV/AIDS, the health-related quality of life was better explained by factors related to economic and social support than those associated with the biological domain. PMID- 22674365 TI - [Prevalence of enterovirus infection in infants in Armenia, Colombia, 2009]. AB - INTRODUCTION: Despite world wide circulation of enteroviruses, little information has accumulated on the circulation of enteroviruses in Colombia. OBJECTIVE: The prevalence of enterovirus circulation was examined in children under 1 year to identify the most common enterovirus serotypes. MATERIALS AND METHODS: Fecal samples were collected from 320 children under 1 year of age who attended a first level health center in the city of Armenia, Colombia, in 2009. Enterovirus detection was performed by reverse transcription reaction and nested polymerase chain reaction (RT-N-PCR) using generic enterovirus primers. Samples testing positive in the RT-N-PCR were inoculated into cell cultures susceptible to enterovirus. All isolates were typed by seroneutralization with Lim-Benyesh Melnick antiserum pools. RESULTS: Overall, enteroviral RNA was detected in 43 of 320 (13.3%; 95% CI: 9.7 to 17.1) fecal samples by RT-N-PCR. Viral isolation was possible in 26 of 43 (60.4%) of the positive samples. Of these, 15 were Coxsackievirus B (eight CVB1, two CVB2, five CVB5) and 11 Echovirus (six E6 and five E30). CONCLUSIONS: The enteroviral circulation in a population on newly bornes up to 1 year old was 13.3%;the most frequent enterovirus was the same as those serotypes most commonly isolated in other parts of the world. The use of RT N-PCR was demonstrably feasible as a tool to monitor the presence of enterovirus in stool samples. PMID- 22674366 TI - [Trypanocidal and cytotoxic activity of extracts of Colombian plants]. AB - INTRODUCTION: The treatment of Chagas disease is based on only two drugs with limited efficacy and significant side effects. The rich biodiversity of the Colombian flora makes bio-prospecting a potential alternative in the search for new antiparasitic drugs. OBJECTIVE: Potential trypanocidal activity and cytotoxicity was assessed in extracts from 23 Colombian plants. MATERIALS AND METHODS: Extracts of leaves, stems, or of the whole plants were obtained in solvents of a range of polarities. The activity against Trypanosoma cruzi epimastigotes and the cytotoxicity were evaluated by the MTT enzymatic micro method. Extracts active against epimastigotes and with low cytotoxicity were also tested on trypomastigotes and intracellular amastigotes. RESULTS: Among the extracts, biological activity was confirmed in 4 species. The extracts were active on epimastigotes and trypomastigotes; one was active also against amastigotes. The latter extract was isolated from the plant Hieronyma antioquensis and presented IC(50) of 3.1 mg/ml for epimastigotes, 11.5 mg/ml for trypomastigotes and 2.9 mg/ml for amastigotes. The selectivity indexes were 25, 7, and 27 respectively. CONCLUSIONS: The extract from H. antioquensis proved a promising candidate for Chagas disease treatment. Futhermore, the MTT enzymatic micromethod was a useful tool for screening biological activity on epimastigotes and other stages of the parasite for further extract trials. PMID- 22674367 TI - [Peripheral facial nerve lesion induced long-term dendritic retraction in pyramidal cortico-facial neurons]. AB - INTRODUCTION: Little evidence is available concerning the morphological modifications of motor cortex neurons associated with peripheral nerve injuries, and the consequences of those injuries on post lesion functional recovery. OBJECTIVE: Dendritic branching of cortico-facial neurons was characterized with respect to the effects of irreversible facial nerve injury. MATERIALS AND METHODS: Twenty-four adult male rats were distributed into four groups: sham (no lesion surgery), and dendritic assessment at 1, 3 and 5 weeks post surgery. Eighteen lesion animals underwent surgical transection of the mandibular and buccal branches of the facial nerve. Dendritic branching was examined by contralateral primary motor cortex slices stained with the Golgi-Cox technique. Layer V pyramidal (cortico-facial) neurons from sham and injured animals were reconstructed and their dendritic branching was compared using Sholl analysis. RESULTS: Animals with facial nerve lesions displayed persistent vibrissal paralysis throughout the five week observation period. Compared with control animal neurons, cortico-facial pyramidal neurons of surgically injured animals displayed shrinkage of their dendritic branches at statistically significant levels. This shrinkage persisted for at least five weeks after facial nerve injury. DISCUSSION: Irreversible facial motoneuron axonal damage induced persistent dendritic arborization shrinkage in contralateral cortico-facial neurons. This morphological reorganization may be the physiological basis of functional sequelae observed in peripheral facial palsy patients. PMID- 22674368 TI - Kinetic analysis of gene expression during mycelium to yeast transition and yeast to mycelium germination in Paracoccidioides brasiliensis. AB - INTRODUCTION: Paracoccidioidomycosis is an endemic systemic mycosis caused by Paracoccidioides brasiliensis, a thermally dimorphic fungus that in tissues and cultures at 37 degrees C grows as a yeast while at lower temperatures (less than 24 degrees C) it becomes a mold; however the genes that rule these processes and their expression are poorly understood. OBJECTIVE: This research focused on the kinetic expression of certain genes in P. brasiliensis throughout the dimorphic process, one that involves the transition from the mycelium to yeast forms and the germination from the yeast to mycelium form. MATERIALS AND METHODS: A real time quantitative polymerase chain reaction (RT-qPCR) was optimized to measure the expression of ten genes connected with diverse cellular functions including cell synthesis and wall structure, oxidative stress response, heat shock response, metabolism, proteins' processing, solute transport across the cell membrane and signal transduction pathways at different time points during the mycelia to yeast transition, as well as in the yeast to mycelia germination processes. RESULTS: Genes involved in cell synthesis and wall structure, metabolism and signal transduction were differentially expressed and highly up regulated during the yeast to mycelia germination process; on the other hand, genes involved in heat shock response, cell synthesis and wall structure were highly up-regulated during the mycelia to yeast transition process. The remaining genes were differentially regulated during both processes. CONCLUSION: In this work the up-regulation of certain genes involved in the morphological changes occurring in P. brasiliensis yeast and mycelia forms were confirmed, indicating that these biological processes play an important role during the host-pathogen interactions, as well as in the fungus adaptation to environmental conditions. PMID- 22674369 TI - [Absence of occult hepatitis B in Colombian blood donors]. AB - INTRODUCTION: In Colombian blood banks, screening for the surface antigen of hepatitis B is mandatory in all units collected. Testing of antibody against core antigens is not administered, although this method may be useful to detect donors infected with the hepatitis B virus. OBJECTIVE: The prevalence of occult hepatitis B was determined by applying a full-serological profile of hepatitis B virus to blood samples of blood donors. MATERIALS AND METHODS: Between April 2008 and October 2009, a prospective cross sectional study was conducted using 628 samples from donors to blood banks located in four Colombian cities. Prevalence for hepatitis B had been previously recorded for these cities. Serological screening was performed for the complete virus; then nucleic acid amplification was tested in sera that were anti-HBc reactive and with a titer of anti-HBs <=30 mUI/ml. RESULTS: Of the 628 samples tested, 129 met the serological criteria established to be tested nucleic acid amplification. None of them demonstrated evidence of nucleic acid amplification of hepatitis B virus. CONCLUSIONS: This is the first study in Colombia to detect the presence of blood donors that may be occult hepatitis B carriers. None was detected. PMID- 22674370 TI - [Serum platelet-activating factor acetylhydrolase activity in dengue patients of African or mestizo descendency]. AB - INTRODUCTION: Severe dengue infection is characterized by enhanced vascular permeability produced by cytokines and biochemical mediators. One of these mediators is the platelet-activating factor. Degradation of platelet-activating factor is accomplished by its specific acetylhydrolase. Down or up regulation of this enzyme has been linked to several diseases. However, the role of this enzyme in dengue infection is unknown, a well as whether differential activity occurs by ethnic group. OBJECTIVE: The activity of the platelet-activating factor acetylhydrolase was compared in patients infected with dengue virus in two ethnic groups. MATERIAL AND METHODS: A descriptive, prospective and longitudinal study was made in two states of Colombia (Antioquia and Choco). Serum samples were taken from 43 mestizo patients and 33 patients of African descent, each taken during five consecutive days of the acute dengue phase. A second serum sample was taken during the convalescent phase. RESULTS: The mestizo patients showed higher frequency of dengue hemorrhagic fever than the patients of African descent (23.3% vs. 12.1%, p=0.25). The serum activity of the platelet-activating factor acetylhydrolase was higher in African descendents than in mestizos (0.89, CI: 0.72-1.10 vs. 0.76 CI: 0-1.03, p<0.001). This relationship is maintained for occurence of dengue fever (0.89, CI: 0.73-1.10 vs. 0.73, CI: 0-1.05, p<0.001), but not significant for dengue hemorrhagic fever (0.88, CI: 0.69-1.12 vs. 0.83, CI: 0.71-1.08, p=0.89). CONCLUSION. An increased production of platelet activating factor-acetylhydrolase occurs in the serum of dengue-infected African descendants. However, a study of the frequencies of polymorphisms for this enzyme will permit more conclusive support for these observations. PMID- 22674371 TI - Surgeons overestimate the risk of malignancy in thyroid nodules, evaluation of subjective estimates using a bayesian analysis. AB - INTRODUCTION: Thyroid nodules are the most common endocrine condition treated by surgeons. The main purpose of the evaluation of a thyroid nodule is to rule out a carcinoma. Medical decisions concerning thyroid nodules are highly influenced by subjective beliefs. OBJECTIVE: To assess the subjective probabilities of malignancy that are assigned to the clinical characteristics of a patient with a thyroid nodule in order to determine the degree of influence that these probabilities have on the final clinical suspicion of malignancy compared with objective data. MATERIAL AND METHODS: A bayesian analysis was designed to predict the risk of malignancy of a thyroid nodule based on the causal relationship between the demographic and clinical risk factors that are detected during the first consultation. A model with demographic and clinical variables using general surgeons as experts was developed. RESULTS: The highest probability of malignancy (94%) was assigned to the pooled case of a male who was older than 60 years, with dysphonia, dysphagia, accelerated growth rate of the nodule and previous neck radiotherapy and who had a relative with thyroid cancer as well as multiple nodules that were larger than 1 cm and with hard consistency and palpable neck lymph nodes. For low risk cases in which the nodule characteristics are not suggestive of malignancy, the probability of malignancy assigned by clinicians was 33.59%; for high risk cases this was 75.54%. CONCLUSION: Surgeons make diagnostic decisions based on subjective beliefs that do not necessarily correspond to the objective measures of the characteristics of the nodules. PMID- 22674372 TI - Modulation of the norfloxacin resistance in Staphylococcus aureus by Croton campestris A. and Ocimum gratissimum L. AB - INTRODUCTION: Some species of Staphylococcus are often recognized as etiological agents of many animal and human opportunistic infections. This study is the first test of change in resistance of antibiotic activity by Croton campestris A. and Ocimum gratissimum L. against multiresistant strains of Staphylococcus aureus. OBJECTIVE: In this study, the hexane and methanol extract of Croton campestris A. and Ocimum gratissimum L. was tested for antibacterial activity alone and in combination with norfloxacin against the strain SA1199B. MATERIALS AND METHODS: The minimum inhibitory concentration (MIC) and the modulatory effect of extracts was assayed using microtitre assay. RESULTS: By the fact of the MIC observed was not clinically relevant (MIC= 512 to >=1.024 ug/ml), the antibiotic activity of norfloxacin was enhanced when this antibiotic was combined with sub-inhibitory concentrations of extracts, mainly the hexane extracts. CONCLUSIONS: These results indicate that the assayed extracts present compounds that can be used as a putative efflux pump inhibitor, indicating that Croton campestris A. and Ocimum gratissimum L. can be a source of plant derived products with antibiotic modifier activity. PMID- 22674373 TI - Supervised selection of single nucleotide polymorphisms in chronic fatigue syndrome. AB - INTRODUCTION: The different ways for selecting single nucleotide polymorphisms have been related to paradoxical conclusions about their usefulness in predicting chronic fatigue syndrome even when using the same dataset. OBJECTIVE: To evaluate the efficacy in predicting this syndrome by using polymorphisms selected by a supervised approach that is claimed to be a method that helps identifying their optimal profile. MATERIALS AND METHODS: We eliminated those polymorphisms that did not meet the Hardy-Weinberg equilibrium. Next, the profile of polymorphisms was obtained through the supervised approach and three aspects were evaluated: comparison of prediction accuracy with the accuracy of a profile that was based on linkage disequilibrium, assessment of the efficacy in determining a higher risk stratum, and estimating the algorithm influence on accuracy. RESULTS: A valid profile (p<0.01) was obtained with a higher accuracy than the one based on linkage disequilibrium, 72.8 vs. 62.2% (p<0.01). This profile included two known polymorphisms associated with chronic fatigue syndrome, the NR3C1_11159943 major allele and the 5HTT_7911132 minor allele. Muscular pain or sinus nasal symptoms in the stratum with the profile predicted V with a higher accuracy than those symptoms in the entire dataset, 87.1 vs. 70.4% (p<0.01) and 92.5 vs. 71.8% (p<0.01) respectively. The profile led to similar accuracies with different algorithms. CONCLUSIONS: The supervised approach made it possible to discover a reliable profile of polymorphisms associated with this syndrome. Using this profile, accuracy for this dataset was the highest reported and it increased when the profile was combined with clinical data. PMID- 22674374 TI - Rituximab mediates loss of CD19 on B cells in the absence of cell death. AB - OBJECTIVE: To evaluate loss of the B cell-specific marker CD19 after the addition of rituximab (RTX) to healthy donor blood and to determine the role of complement mediated cytotoxicity in these cells. METHODS: Whole blood and peripheral blood mononuclear cells (PBMCs) from healthy donors were evaluated for the loss of CD19 in the presence of RTX using flow cytometry. The effect of complement on CD19 loss was examined using serum-free media, C3- and C5-deficient sera, and a C5 blocking antibody. Evidence of B cell death was evaluated by measuring messenger RNA (mRNA) levels as well as by flow cytometry. Transfer of CD19 antigen to monocytes and neutrophils was evaluated by flow cytometry and confocal microscopy. RESULTS: RTX induced a rapid decrease in CD19 count (mean 51%; n = 37) in PBMCs. This reduction occurred in the absence of complement. Despite the decrease in CD19 expression, B cell death did not occur, as evidenced by a lack of change in CD19 or CD20 mRNA levels and a lack of change in CD19 levels determined by intracellular staining and through the use of viability dyes. The CD19 antigen was shown to be transferred to monocytes and neutrophils in an Fc dependent manner. CONCLUSION: Our findings indicate that the addition of RTX to healthy donor PBMCs in vitro results in complement-independent loss of CD19 without causing B cell death. CD19 is transferred from B cells to monocytes and neutrophils during shaving of the RTX-CD20 complex in an Fc-dependent manner. These data suggest that monitoring the effect of RTX by measuring the CD19+ cell count may be compromised by this activity. PMID- 22674375 TI - Parental divorce and adult longevity. AB - OBJECTIVE: Life course research has established associations between adverse childhood events and later life health. We examine the relationship of experiencing parental divorce before the age of 16 and survival across 34 years of adulthood. METHODS: Analysis of panel data from a USA-based survey of 6,928 adults residing in Alameda County, California in 1965. Cox regression was used to examine associations between parental divorce and longevity. RESULTS: Controlling for age, race/ethnicity, gender, and childhood socioeconomic position, respondents who recalled a parental divorce during childhood had increased risk of mortality compared to those with no separation. The association was stronger for premature mortality and deaths due to cardiovascular disease. Divorce in childhood was also associated with lowered adult education, fewer social network ties, more depression, and worse health practices. These factors appeared to explain the association with longevity. CONCLUSION: Parental divorce in childhood is associated with lowered well-being in adulthood and long-term survival. Early prevention and health promotion efforts may be warranted for children who experience parental divorce or discord as a means of supporting enhanced trajectories of health and well-being. PMID- 22674376 TI - Unfavourable life-course social gradient of coronary heart disease within Spain: a low-incidence welfare-state country. AB - OBJECTIVE: Social position has yet to be established as a risk factor of coronary heart disease (CHD). Our aim was to investigate an individual life-course social position gradient link with CHD incidence in the EPIC-Spain cohort. METHODS: 41,066 participants, mostly 30-65 years old, and free of cardiovascular disease at baseline (1992-1996) were followed up for a mean of 10.4 years. A combined score of paternal occupation in childhood and own adult education was used to assess individual life-course risk accumulation. Hazard ratios of CHD were estimated using Cox models, stratifying by centre, and age, and adjusting for cardiovascular risk factors. RESULTS: 583 participants (80 % men) developed a definite CHD event. Paternal occupational class IV was associated with CHD in all models in men. The educational gradient remained significant after adjusting for diet and physical activity (p = 0.01). All adjusted risk of incident CHD rose by 23 % (95 % CI 6-42 %) per category increase of life-course social position score in men. No significant associations were found in women. CONCLUSIONS: Individual life-course social position gradient was adversely related to incident CHD in Spanish men. PMID- 22674377 TI - Improvement of enzymatic stability and intestinal permeability of deuterohemin peptide conjugates by specific multi-site N-methylation. AB - The deuterohemin-peptide conjugate, DhHP-6 (Dh-beta-AHTVEK-NH(2)), is a microperoxidase mimetic, which has demonstrated substantial benefits in vivo as a scavenger of reactive oxygen species (ROS). In this study, specific multi-site N methylated derivatives of DhHP-6 were designed and synthesized to improve metabolic stability and intestinal absorption, which are important factors for oral delivery of therapeutic peptides and proteins. The DhHP-6 derivatives were tested for (1) scavenging potential of hydrogen peroxide (H(2)O(2)); (2) permeability across Caco-2 cell monolayers and everted gut sacs; and (3) enzymatic stability in serum and intestinal homogenate. The results indicated that the activities of the DhHP-6 derivatives were not influenced by N methylation, and that tri-N-methylation of DhHP-6 could significantly increase intestinal flux, resulting in a two- to threefold higher apparent permeability coefficient. In addition, molecules with N-methylation at selected sites (e.g., Glu residue) showed high resistance against proteolytic degradation in both diluted serum and intestinal preparation, with 50- to 140-fold higher half-life values. These findings suggest that the DhHP-6 derivatives with appropriate N methylation could retain activity levels equivalent to that of the parent peptide, while showing enhanced intestinal permeability and stability against enzymatic degradation. The tri-N-methylated peptide Dh-beta-AH(Me)T(Me)V(Me)EK NH(2) derived from this study may be developed as a promising candidate for oral administration. PMID- 22674378 TI - Gene expression profiling of hybridoma cells after bursal-derived bioactive factor BP5 treatment. AB - Bursa of Fabricius is the acknowledged vital humoral immune system for B cell differentiation and antibody production. To study the molecular mechanism underlying the effect of bursal-derived BP5, we used gene microarray to analyze the genomic expression profiling of BP5-treated hybridoma cells. BP5 exhibited an immunomodulatory effect on antibody production in hybridoma cells and induced alterations in the gene expression profiles related to the immune-related biological processes, such as T cell activation and proliferation, B cell activation, B cell-mediated immunity, and cytokines cytokine production involved in immune response. In addition, 26 biological pathways associated with immunomodulatory functions were regulated in BP5-treated hybridoma cells, in which p53 signal pathway played an important role in antitumor. Among these regulated genes, 12 differentially expressed genes were verified by qRT-PCR. The activation of p53 activity by BP5 was further confirmed by p53 luciferase reporter assay and p53 expression. Our data revealed that bursal-derived BP5 could regulate various immune-related cellular processes, including antitumor factor p53 signal pathway, perhaps partially accounting for the reported immunomodulatory roles and novel antiproliferation on tumor cells functions of bursal-derived bioactive factor BP5. PMID- 22674379 TI - p62/sequestosome 1 binds to TDP-43 in brains with frontotemporal lobar degeneration with TDP-43 inclusions. AB - Ubiquitin-positive cytoplasmic inclusions are consistently found in various neurodegenerative diseases. As with ubiquitin, anti-p62/SQSTM1 (referred to as p62) antibody clearly immunostains these inclusions. p62 has a ubiquitin associated domain at the carboxyl terminus and thereby interacts with ubiquitinated and misfolded proteins. Here we immunoprecipitated endogenous p62 in the cerebral cortex from patients with frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) and found that p62 coimmunoprecipitated several proteins, including TDP-43, which is a major disease protein in FTLD-TDP. Unexpectedly, p62 immunoprecipitated a smaller amount of TDP-43 in FTLD-TDP compared with controls. Further analyses showed that p62 physiologically binds to TDP-43 and likely is involved in degradation of TDP-43 with 35-kDa, but not full length TDP-43. Our results suggest that the interaction of TDP-43 and p62 is disrupted and may participate in the pathogenesis of TDP-43 proteinopathy. PMID- 22674380 TI - P-glycoprotein (ABCB1) inhibited network of mitochondrion transport along microtubule and BMP signal-induced cell shape in chimpanzee left cerebrum by systems-theoretical analysis. AB - We constructed the significant low-expression P-glycoprotein (ABCB1) inhibited transport and signal network in chimpanzee compared with high-expression (fold change >=2) the human left cerebrum in GEO data set, by using integration of gene regulatory activated and inhibited network inference method with gene ontology (GO) analysis. Our result showed that ABCB1 transport and signal upstream network RAB2A inhibited ABCB1, and downstream ABCB1-inhibited SMAD1_2, NCK2, SLC25A46, GDF10, RASGRP1, EGFR, LRPPRC, RASSF2, RASA4, CA2, CBLB, UBR5, SLC25A16, ITGB3BP, DDIT4, PDPN, RAB2A in chimpanzee left cerebrum. We obtained that the different biological processes of ABCB1 inhibited transport and signal network repressed carbon dioxide transport, ER to Golgi vesicle-mediated transport, folic acid transport, mitochondrion transport along microtubule, water transport, BMP signaling pathway, Ras protein signal transduction, transforming growth factor beta receptor signaling pathway in chimpanzee compared with the inhibited network of the human left cerebrum, as a result of inducing inhibition of mitochondrion transport along microtubule and BMP signal-induced cell shape in chimpanzee left cerebrum. Our hypothesis was verified by the same and different biological processes of ABCB1 inhibited transport and signal network of chimpanzee compared with the corresponding activated network of chimpanzee and the human left cerebrum, respectively. PMID- 22674381 TI - Characteristics and influencing factors of CD19+ B cell reconstitution in patients following haploidentical/mismatched hematopoietic stem cell transplantation. AB - In patients undergoing hematopoietic stem cell transplantation (HSCT), B cells exert important, prolonged effects that provide protection from infection. In this study, we analyzed characteristics and influencing factors of CD19+ B cell reconstitution in 83 patients who underwent unmanipulated haploidentical/mismatched blood and bone marrow transplantation. Of these patients, 45 % showed a normal CD19+ B cell count at +360 days. Factors associated with lower CD19+ B cell levels were as follows: aGVHD grades II-IV had a trend to affect CD19+ B cell reconstitution at +180 days; clinically extensive cGVHD was significantly associated with CD19+ B cell deficiency at +360 days and serum IgG level at +180 and +360 days; cytomegalovirus (CMV) infection occurred after +38 days was correlated with lower B cell level at both +90 and +360 days, while those occurred before +38 days did not show this effect; glucocorticoids used around +90 and +180 days was associated with lower CD19+ B cell levels at +90 and +360 days, respectively, especially in patients that did not experience extensive cGVHD. In contrast, the number of HLA-mismatched locus positively correlated with CD19+ B cell at +90 days and serum IgG level at +180 days. In conclusion, CD19+ B cell recovery after haploidentical/mismatched HSCT was mainly influenced by GVHD and/or its treatment, CMV infection that occurred later (after +38 days) and use of glucocorticoids. Improvement of B cell recovery is likely to be achieved through effective prophylaxis of GVHD, minimized use of glucocorticoids, and preemptive treatment of CMV infection occurring after +38 days. More HLA-mismatched loci may initiate a stronger humoral response toward alloantigens >180 days after HSCT, which may be beneficial for the eradication of minimal residual disease and protection from infection. PMID- 22674382 TI - Down-regulation of hematopoiesis master regulator PU.1 via aberrant methylation in chronic myeloid leukemia. AB - The PU.1 transcription factor is a crucial regulator of hematopoiesis, and its expression is altered in various leukemic processes. It has been shown that expression of PU.1 is severely impaired in patients with chronic myeloid leukemia (CML), but the mechanism underlying this effect remains unknown. Through bisulfite sequencing, semi-quantitative PCR, and indirect immunofluorescence and Western blot techniques, we found aberrant methylation in the promoter region of transcription factor PU.1 in CML patients both in the chronic and blast crisis phases, as well as in the CML blast K562 cell line. Of these, several CpG sites were more highly methylated in blast crisis than chronic phase, while no methylation of these sites was observed in healthy individuals. Interestingly, CML patients achieved complete cytogenetic remission under imatinib mesylate treatment, but the aberrant methylation status of PU.1 was not reversed. Down regulation of PU.1 expression at the mRNA and protein levels was also observed in association with aberrant methylation. Thus, for the first time, we have revealed a potential epigenetic modification of PU.1 in CML, which may be responsible for the down-regulation of PU.1. These data suggest that aberrant methylation of PU.1 may play a role in CML pathogenesis, and may therefore serve as a useful biomarker and potential target for demethylating drugs. PMID- 22674383 TI - Effects of an exogenous xylanase gene expression on the growth of transgenic rice and the expression level of endogenous xylanase inhibitor gene RIXI. AB - BACKGROUND: Xylanases have attracted considerable interest in recent years owing to their various applications in industry and agriculture. The use of transgenic plants to produce xylanases is a less expensive alternative to biotechnological programmes. The aim of this study was to elucidate whether introducing a foreign xylanase gene ATX into rice had any adverse effect on plant growth and development. RESULTS: A recombinant xylanase gene ATX was introduced into rice variety Zhonghua 11 through Agrobacterium-mediated transformation. The T2 generation of transgenic rice was compared with the control (non-transgenic plants). Exogenous xylanase gene ATX was expressed in rice, and all examined transgenic lines exhibited xylanase activity. The transgenic lines (T2, 'X1-3' and 'X2-5') appeared to grow and develop normally. There were no differences in net photosynthetic rate between transgenic rice lines ('X1-3' and 'X2-5') and wild type (WT) rice plants at the heading/flowering stage. Xylanases are key enzymes in the degradation of plant cell walls. Cell wall composition analysis showed that that there were no changes in cell wall polysaccharides in the root apex but some alterations in leaves in transgenic rice plants. The results also showed that the expression of exogenous xylanase gene ATX in rice would increase the expression of endogenous xylanase inhibitor gene RIXI, which could play a role in plant defence. Thus the stress resistance of transgenic rice plants might be improved. CONCLUSION: Exogenous xylanase gene ATX could be successfully expressed in rice, and the exogenous protein had no apparent harmful effects on growth and development in transgenic rice plants. PMID- 22674384 TI - Ex vivo pharmacology of surgical samples of the uterosacral ligament. Part II: Effects of oxytocin and relaxin on arteries and vascular plexus. AB - AIMS: The uterosacral ligament (USL) contains prominent vessels, the function of which is unknown. Here we study the relationship between smooth muscle of the USL and the vascular bundles. METHODS: Native samples of arteries and vascular bundles were mounted in a perfusion chamber under the stereomicroscope. The effects of noradrenalin, carbachol, oxytocin, and relaxin were monitored by digital time-lapse video and quantified by image processing. RESULTS: Arteries were adrenergic and the smooth muscle in the adventitia cholinergic. Relaxin-2 shifted the dose response curve of noradrenalin to the right and widened the arterial lumen within 30 min. Oxytocin induced contraction of the adventitial smooth muscle leading to a slow opening of the artery. In a vascular bundle the differential pattern of both reactivities was demonstrated. CONCLUSIONS: In the USL the smooth muscle extends into the adventitial layer of blood vessels and forms a functional unit with the vascular plexus, which is regulated by relaxin and oxytocin. PMID- 22674386 TI - eHealth: easing translation in health care. AB - Our complex healthcare systems are fragmented, and their functioning, both in terms of efficiency and quality, are plagued by multiple discontinuities. eHealth has the potential to ease transitions between the many settings and stakeholders of healthcare. eHealth can improve the continuity of healthcare information flow, can facilitate the re-engineering of care processes so that they become much more patient-owned and patient-controlled, and can enable better ways of accessing and producing care. Such capabilities evolve with the development of our information and knowledge-based society, reflected by the various generations of the world wide-web. Starting with the "read-only Web" where the main task was to give access to health information, it has evolved into the "social Web" and provides support of patient-centred, collaborative care, and is reaching a stage where pervasive computing tools can intelligently partner with citizens to help them take better care of their health. PMID- 22674388 TI - The antiapoptotic effect of galectin-3 in human endometrial cells under the regulation of estrogen and progesterone. AB - Galectin-3 (Gal-3), a ubiquitously expressed gene involved in many cellular processes, has been recently recognized as a factor related to endometrial receptivity. However, the precise biological function of Gal-3 in the endometrium and its regulation is still unclear. In this study, we detected the antiapoptotic role of Gal-3 in endometrial cells and the expression of Gal-3 regulated by estrogen and progesterone. We found that expression of Gal-3 increased when exposed to the apoptosis inducer staurosporine. Gal-3-silenced endometrial cells were more sensitive to the apoptosis inducer. Estradiol (E2) and progesterone (P4) up-regulated Gal-3 expression, which in turn decreased the apoptotic rate of endometrial cells. Our results strongly suggested that hormonal activation of Gal 3 by E2 and P4 is involved in inhibiting endometrial cell apoptosis, playing key roles in embryo implantation. PMID- 22674387 TI - Comprehensive analysis of genes expressed by rare microchimeric fetal cells in the maternal mouse lung. AB - During pregnancy, cells from each fetus travel into the maternal circulation and organs, resulting in the development of microchimerism. Identification of the cell types in this microchimeric population would permit better understanding of possible mechanisms by which they affect maternal health. However, comprehensive analysis of fetal cells has been hampered by their rarity. In this study, we sought to overcome this obstacle by combining flow cytometry with multidimensional gene expression microarray analysis of fetal cells isolated from the murine maternal lung during late pregnancy. Fetal cells were collected from the lungs of pregnant female mice. cDNA was amplified and hybridized to gene expression microarrays. The resulting fetal cell core transcriptome was interrogated using multiple methods including Ingenuity Pathway Analysis, the BioGPS gene expression database, principal component analysis, the Eurexpress gene expression atlas, and primary literature. Here we report that small numbers of fetal cells can be flow sorted from the maternal lung, facilitating discovery driven gene expression analysis. We additionally show that gene expression data can provide functional information about fetal cells. Our results suggest that fetal cells in the murine maternal lung are a mixed population, consisting of trophoblasts, mesenchymal stem cells, and cells of the immune system. Detection of trophoblasts and immune cells in the maternal lung may facilitate future mechanistic studies related to the development of immune tolerance and pregnancy related complications, such as pre-eclampsia. Furthermore, the presence and persistence of mesenchymal stem cells in maternal organs may have implications for long-term postpartum maternal health. PMID- 22674389 TI - Placental, renal, and ileal sulfate transporter gene expression in mouse gestation. AB - Sulfate is important for mammalian growth and development. During pregnancy, maternal circulating sulfate levels increase by 2-fold, enhancing sulfate availability to the fetus. We used quantitative real-time PCR to determine sulfate transporter mRNA levels during mouse gestation in three tissues: kidney and ileum, to identify transporters involved in sulfate absorption and maintaining high maternal circulating sulfate level; and placenta, to build a model of directional sulfate transport from mother to fetus. In the kidney, Slc13a1 and Slc26a1 were the most abundant sulfate transporter mRNAs, which increased by ~2-fold at E4.5 or E6.5, whereas lower levels of Slc26a2, Slc26a6, and Slc26a7 mRNA increased by ~3- to 6-fold from E4.5. Ileal sulfate transporter mRNA levels were not increased in gestation, but slight decreases (by ~30-40%) were found for Slc26a3 and Slc26a6. In placentae, Slc13a4 and Slc26a2 mRNAs were most abundant, with levels increasing from E10.5 and peaking (~8-fold) from E14.5 to E18.5, whereas Slc26a1 increased by ~3-fold at E18.5. The spatial expression of placental mRNAs was determined by in situ hybridization showing Slc13a4 and Slc26a6 in yolk sac, Slc26a1 in spongiotrophoblasts, and Slc13a4, Slc26a2, Slc26a3, and Slc26a7 in the labyrinthine layer. Within the labyrinth, cell specific staining revealed Slc13a4 expression in syncytiotrophoblast-II (SynT-II) and Slc26a2 in SynT-I. Together, these data show kidney Slc13a1 and Slc26a1 and placental Slc13a4 and Slc26a2 to be the most abundant sulfate transporter mRNAs in mouse gestation, which likely play important physiological roles in maintaining high maternal serum sulfate levels during pregnancy and mediating sulfate supply to the fetus. PMID- 22674391 TI - Role of integrin switch and transforming growth factor Beta 3 in hypoxia-induced invasion inhibition of human extravillous trophoblast cells. AB - The physiological hypoxic condition favors the angiogenesis in the placenta. However, it remains unclear how hypoxia regulates the invasion of human extravillous trophoblast cells. In the present study, we first showed that alpha5 integrin expression increased and alpha1 integrin expression decreased in human extravillous trophoblast cells cultured in 1% oxygen as compared with control cells cultured in 8% oxygen. Further data showed that the neutralizing antibody against alpha5 integrin increased the invasion of human extravillous trophoblast cells and the neutralizing antibody against alpha1 integrin inhibited the invasion of human extravillous trophoblast cells. Human extravillous trophoblast cells cultured in 1% oxygen showed reduced invasive capacity, which can be effectively blocked by alpha5 integrin neutralizing antibody. Moreover, human extravillous trophoblast cells exposed to 1% oxygen demonstrated increased expression of transforming growth factor-beta3 (TGFB3), and recombinant human TGFB3 inhibited the invasion of human extravillous trophoblast cells in a dose dependent manner. The neutralizing antibodies against alpha5 integrin and TGFB3 markedly abrogated hypoxia-induced invasion inhibition in human extravillous trophoblast cells. These data indicate that hypoxia may inhibit the invasion of human extravillous trophoblast cells through inducing the integrin switch from alpha1 integrin to alpha5 integrin and promoting TGFB3 expression. PMID- 22674390 TI - Compartmentalizing proximal FGFR1 signaling in ovine placental artery endothelial cell caveolae. AB - Caveolae orchestrate the dominant placental angiogenic growth factor fibroblast growth factor 2 (FGF2) signaling primarily via FGF receptor 1 (FGFR1) in placental artery endothelial cells; however, how the proximal FGF2/FGFR1 signaling is organized in the caveolae is obscure. We have shown in the present study that the FGFR substrate 2alpha (FRS2alpha) is physically associated with FGFR1, and both are targeted to the caveolae via interaction with caveolin-1 in ovine fetoplacental artery endothelial cells. Treatment with FGF2 rapidly stimulated time- and concentration-dependent FRS2alpha tyrosine phosphorylation and recruited the cytosolic growth factor receptor-bound protein 2 (GRB2)-GRB2 associated binding protein 1 (GAB1) complex to the caveolae, where they formed a ternary complex with FRS2alpha. Disruption of caveolae by cholesterol depletion with methyl-beta-cyclodextrin inhibited FGF2-induced FRS2alpha tyrosine phosphorylation, and it blocked the FGF2-induced recruitment of GRB2 and GAB1 to the caveolae and formation of the FRS2alpha-GRB2-GAB1 complex in the caveolae, as well as activation of the PI3K/AKT1 and MAPK1/2 pathways. Thus, these findings have demonstrated that the proximal fibroblast growth factor (FGF2/FGFR1) signaling is compartmentalized in the placental endothelial caveolae via the FGFR substrate 2alpha that mediates formation of a FRS2alpha-GRB2-GAB1 complex. PMID- 22674392 TI - Stage-specific effects of androgens and estradiol-17beta on the development of late primary and early secondary ovarian follicles of coho salmon (Oncorhynchus kisutch) in vitro. AB - An in vitro system was used to analyze the effects of sex steroids on the development of primary (late perinucleolar stage) and early secondary, previtellogenic (early cortical alveolus stage) ovarian follicles of coho salmon cultured for up to 21 days. Late perinucleolar-stage follicles increased significantly in size after 7 days of treatment with low concentrations of 11 ketotestosterone (11-KT), a nonaromatizable androgen. An androgen receptor antagonist (flutamide) inhibited this growth-promoting effect, and the highest concentration resulted in atresia of follicles, implicating androgens as survival factors at this stage. Testosterone (T) was less effective than 11-KT in promoting growth, but blocking aromatization with exemestane resulted in a growth response similar to that of 11-KT. Estradiol-17beta (E2) had no effect on growth at this stage. After 21 days of culture, E2 was the most potent steroid in increasing the number of follicles containing cortical alveoli and the number of cortical alveoli within those follicles. At the early cortical alveolus stage, low doses of E2 promoted growth and strongly stimulated synthesis of cortical alveoli, actions that were inhibited by an estrogen receptor antagonist (tamoxifen). 11-KT displayed moderate growth-promoting effects, and 11-KT and T stimulated moderate to substantial increases in abundance of cortical alveoli. This study shows that the predominant role of androgens is the promotion of growth of late perinucleolar-stage follicles, while E2 stimulates both the growth and accumulation of cortical alveoli in early cortical alveolus-stage follicles. PMID- 22674393 TI - Involvement of bone marrow-derived vascular progenitor cells in neovascularization during formation of the corpus luteum in mice. AB - Neovascularization is necessary for formation of the corpus luteum (CL) and includes angiogenesis and vasculogenesis. Vasculogenesis is the formation of new blood vessels by bone marrow-derived endothelial progenitor cells. Here we investigated whether vasculogenesis occurs in neovascularization during CL formation. Mice transplanted with bone marrow from transgenic mice expressing green fluorescent protein (GFP) were injected with equine chorionic gonadotropin and human chorionic gonadotropin (hCG) to induce ovulation and subsequent CL formation. Immunohistochemistry was performed on the ovaries obtained before hCG injection and at 6, 12, and 24 h after hCG injection using antibodies for CD34 or CD31 (an endothelial cell marker), platelet-derived growth factor receptor beta (PDGFR-beta, a pericyte marker), F4/80 (a macrophage marker), and GFP (a bone marrow-derived cell marker). Cells immunostained for CD34, PDGFR-beta, F4/80, and GFP were present in the theca cell layer of the preovulatory follicle before hCG injection. Each of these cell types invaded the granulosa cell layer after hCG injection, and a number of them were observed in the CL 24 h after hCG injection. Fluorescence-based immunohistochemistry or double immunohistochemical staining revealed that a few CD34/CD31-positive cells and PDGFR-beta-positive cells were also positive for GFP in the preovulatory follicle and CL, and that many of the GFP-positive cells recruited to the CL during CL formation were F4/80-positive macrophages. In conclusion, bone marrow-derived vascular progenitor cells and macrophages contribute to neovascularization during CL formation. PMID- 22674394 TI - Analyses of the involvement of PKA regulation mechanism in meiotic incompetence of porcine growing oocytes. AB - Mammalian growing oocytes (GOs) lack the ability to resume meiosis, although the molecular mechanism of this limitation is not fully understood. In the present study, we cloned cDNAs of cAMP-dependent protein-kinase (PKA) subunits from porcine oocytes and analyzed the involvement of the PKA regulation mechanism in the meiotic incompetence of GOs at the molecular level. We found a cAMP independent high PKA activity in GOs throughout the in vitro culture using a porcine PKA assay system we established, and inhibition of the activity by injection of the antisense RNA of the PKA catalytic subunit (PKA-C) induced meiotic resumption in GOs. Then we examined the possibility that the amount of the PKA regulatory subunit (PKA-R), which can bind and inhibit PKA-C, was insufficient to suppress PKA activity in GOs because of the overexpression of two PKA-Rs, PRKAR1A and PRKAR2A. We found that neither of them affected PKA activity and induced meiotic resumption in GO although PRKAR2A could inhibit PKA activity and induce meiosis in cAMP-treated full-grown oocytes (FGOs). Finally, we analyzed the subcellular localization of PKA subunits and found that all the subunits were localized in the cytoplasm during meiotic arrest and that PKA-C and PRKAR2A, but not PRKAR1A, entered into the nucleus just before meiotic resumption in FGOs, whereas all of them remained in the cytoplasm in GOs throughout the culture period. Our findings suggest that the continuous high PKA activity is a primary cause of the meiotic incompetence of porcine GOs and that this PKA activity is not simply caused by an insufficient expression level of PKA-R, but can be attributed to more complex spatial-temporal regulation mechanisms. PMID- 22674395 TI - Unique pattern of ORC2 and MCM7 localization during DNA replication licensing in the mouse zygote. AB - In eukaryotes, DNA synthesis is preceded by licensing of replication origins. We examined the subcellular localization of two licensing proteins, ORC2 and MCM7, in the mouse zygotes and two-cell embryos. In somatic cells ORC2 remains bound to DNA replication origins throughout the cell cycle, while MCM7 is one of the last proteins to bind to the licensing complex. We found that MCM7 but not ORC2 was bound to DNA in metaphase II oocytes and remained associated with the DNA until S phase. Shortly after fertilization, ORC2 was detectable at the metaphase II spindle poles and then between the separating chromosomes. Neither protein was present in the sperm cell at fertilization. As the sperm head decondensed, MCM7 was bound to DNA, but no ORC2 was seen. By 4 h after fertilization, both pronuclei contained DNA bound ORC2 and MCM7. As expected, during S-phase of the first zygotic cell cycle, MCM7 was released from the DNA, but ORC2 remained bound. During zygotic mitosis, ORC2 again localized first to the spindle poles, then to the area between the separating chromosomes. ORC2 then formed a ring around the developing two-cell nuclei before entering the nucleus. Only soluble MCM7 was present in the G2 pronuclei, but by zygotic metaphase it was bound to DNA, again apparently before ORC2. In G1 of the two-cell stage, both nuclei had salt-resistant ORC2 and MCM7. These data suggest that licensing follows a unique pattern in the early zygote that differs from what has been described for other mammalian cells that have been studied. PMID- 22674396 TI - Levels of neuroglobin in serum and neurocognitive impairments in Chinese patients with obstructive sleep apnea. AB - PURPOSE: The impact of different severities of obstructive sleep apnea (OSA) on cognition has not well been documented. Neuroglobin, a recently discovered vertebrate protein, shows a neuroprotective function to modulate hypoxic-ischemic brain injury. This study investigated the cognitive function of patients with varying OSA severities and intended to explore the relationship between levels of neuroglobin in serum and cognitive deficits of OSA. METHODS: Sixty Chinese adults aged 18-59 years old were enrolled and categorized into four groups based on apnea-hypopnea index (AHI): primary snoring (n = 7), mild (n = 13), moderate (n = 20), and severe (n = 20) OSA groups. Computer-based neurocognitive tests (including calculation, memory, and attention) and Epworth sleepiness scale were administered before polysomnographic monitoring, and blood sample was taken the next morning. Concentrations of serum neuroglobin were measured using ELISA. RESULTS: No significant difference was observed in cognitive function regardless of OSA severities, but patients with moderate and severe OSA presented significantly more sleepiness than patients with primary snoring and mild OSA. Memory significantly correlated with time spent with oxygen saturation below 90 % during nighttime (T < 90 %), as well as oxygen desaturation index, AHI, or NREM sleep. Calculation correlated significantly with sleepiness and respiratory arousal index. Levels of neuroglobin in serum of patients with varying OSA severities were significant elevated than that of patients with primary snoring. No relationship was found between the neurobehavioral ability index of neurocognitive tests and serum neuroglobin concentrations after controlling for gender, age, and BMI, whereas the unique association between levels of neuroglobin in serum and the scores of auditory digit span test was noted. CONCLUSIONS: Our findings suggest that different neurocognitive domains might specifically correlate to either sleepiness or hypoxemia. Changes of concentrations of neuroglobin in serum may possibly be used as an indicator to monitor the brain damage of OSA. Further investigations are needed to explore the relationship between regulation of neuroglobin in serum and severity of brain damage in OSA. PMID- 22674398 TI - Antioxidant vitamins prevent oxidative and carbonyl stress in an animal model of obstructive sleep apnea. AB - PURPOSE: The aim of our study was to analyze the effects of an antioxidant treatment on markers of oxidative and carbonyl stress in a rat model of obstructive sleep apnea. METHODS: Wistar rats were randomized into six groups according to gender and intervention-sham, intermittent hypoxia, and intermittent hypoxia with treatment by vitamins C and E. Rats underwent tracheostomy. The tracheal cannula was closed for 12 s every minute for 1 h to simulate obstructive sleep apnea-related intermittent hypoxia. In the treatment group, rats received vitamin C and E 24 h prior to surgery. RESULTS: The intervention had a significant effect on advanced oxidation protein products (p = 0.008) and advanced glycation end products-specific fluorescence (p = 0.006) but no effect on malondialdehyde. Oxidation and glycation protein products were higher in intermittent hypoxia groups than in sham and in treated groups. CONCLUSIONS: Antioxidants alleviate oxidative and carbonyl stress in an experimental model of obstructive sleep apnea. Future studies will show whether such treatment has any clinical value regarding cardiovascular complications of sleep apnea syndrome, preferably in patients with low compliance to continuous positive airway pressure. PMID- 22674397 TI - Analysis of systemic and airway inflammation in obstructive sleep apnea. AB - PURPOSE: The presence of both systemic and airway inflammation has been suggested in obstructive sleep apnea (OSA) by increased levels of inflammatory biomarkers in the circulation and respiratory specimens. We aimed to investigate the relationship between systemic and airway inflammation in OSA. METHODS: This study was conducted by simultaneously measuring various biomarkers both in serum and induced sputum of 43 patients. We compared the relationships of these biomarker levels with polysomnographic data and obesity measurements and also investigated their interrelationships between systemic and local compartments. We also assessed the relation of inflammatory markers with proximal airway resistance measured by impulse oscillometry. RESULTS: In multiple regression analyses, each measured serum biomarker [leptin, interleukin-6 (IL-6), IL-8, tumor necrosis factor-alpha (TNF-alpha), and vascular endothelial growth factor (VEGF)] significantly correlated with waist circumference or fat area determined by computed tomography. In contrast, regarding airway inflammation, sputum IL-6, IL 8, TNF-alpha, and VEGF significantly correlated with OSA severity as indicated by the respiratory disturbance index or oxygen desaturation indices. Sputum IL-6, IL 8, TNF-alpha, and VEGF were significantly related to sputum neutrophil number, and sputum IL-8 and TNF-alpha were related to proximal airway resistance independently of body mass index. There were no significant interrelationships between the same biomarkers in serum and induced sputum. CONCLUSIONS: Systemic and airway inflammation in OSA might be differently regulated by OSA itself and comorbid obesity, depending on the type of cytokine. Although we did not find apparent interrelationships between systemic and local compartments, further studies are needed to clarify this concept. PMID- 22674399 TI - The burden of untreated hepatitis C virus infection: a US patients' perspective. AB - BACKGROUND: Hepatitis C virus (HCV) infection is widespread and associated with high economic costs and reduced quality of life, but the impact of untreated HCV infection on patient outcome is not well understood. AIMS: To estimate the impact of untreated HCV infection on work productivity, daily activity, healthcare use, economic costs, and health-related quality of life (HRQoL). METHODS: Respondents to the 2010 US National Health and Wellness Survey (n = 75,000) reporting physician diagnosis of HCV infection but not current or previous treatment (patients) were matched to respondents without HCV infection (controls) by use of propensity scores. Those reporting infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV) were excluded. Self-reported work impairment, activity impairment, healthcare resource use, and HRQoL were compared between patients and controls. Indirect and direct costs were estimated. RESULTS: A total of 306 patients met inclusion criteria. Patients were more impaired at work than controls, with overall work impairment of 26 % versus 15 %, respectively (P < 0.001), mostly because of presenteeism in both groups. Annual productivity losses were estimated at $10,316 per employed patient compared with $5,469 per control (P < 0.001). Patients used more healthcare, with all-cause healthcare costs estimated at $22,818 per patient annually, compared with $15,362 per control (P < 0.001). HRQoL and activity impairment were also worse among patients than controls. CONCLUSIONS: Untreated HCV infection is associated with substantial economic costs to society, through loss of productivity and increased use of healthcare resources, and with impaired well-being of the patient. PMID- 22674400 TI - Increased susceptibility to severe chronic liver damage in CXCR4 conditional knock-out mice. AB - BACKGROUND: The chemokine SDF-1 and its receptor CXCR4 are essential for the proper functioning of multiple organs. In the liver, cholangiocytes and hepatic progenitor cells (HPCs) are the main cells that produce SDF-1, and SDF-1 is thought to be essential for HPC-stimulated liver regeneration. AIMS: In this study, CXCR4 conditionally targeted mice were used to analyze the role of SDF-1 in chronically damaged liver. METHODS: Chronic liver damage was induced in MxCre CXCR4(f/null) mice and the control MxCre CXCR4(f/wt) mice by CCl(4). Serum markers were analyzed to assess liver function and damage, the number of cytokeratin-positive cells as a measure of HPCs, and the extent of liver fibrosis. Additional parameters relating to liver damage, such as markers of HPCs, liver function, MMPs, and TIMPs were measured by real-time PCR. RESULTS: Serum ALT was significantly higher in MxCre CXCR4(f/null) mice than MxCre CXCR4(f/wt) mice. The number of cytokeratin-positive cells and the area of fibrosis were also increased in the MxCre CXCR4(f/null) mice. The expression of mRNAs for several markers related to hepatic damage and regeneration was also increased in the liver of MxCre CXCR4(f/null) mice, including primitive HPC marker prominin-1, MMP9, TNF-alpha, and alpha-SMA. CONCLUSIONS: MxCre CXCR4(f/null) mice were susceptible to severe chronic liver damage, suggesting that SDF-1-CXCR4 signals are important for liver regeneration and preventing the progression of liver disease. Modulation of SDF-1 may therefore be a promising treatment strategy for patients with chronic liver disease. PMID- 22674401 TI - Diagnosis of hereditary hemochromatosis in the era of genetic testing. AB - BACKGROUND: Homozygous C282Y mutation in HFE gene is responsible for the majority of hereditary hemochromatosis cases. Since 1996 this mutation can be identified by a simple genetic test. AIMS: To determine the clinical presentations in patients with homozygous HFE C282Y mutation and the impact of genetic testing on the time needed for diagnosis. METHODS: A total of 414 patients diagnosed with C282Y homozygous hereditary hemochromatosis before and after the introduction of genetic testing were evaluated regarding symptoms and clinical findings at diagnosis as well as first hemochromatosis-related clinical features in their past medical history. RESULTS: At the time of diagnosis, the predominant symptom was joint pain, in particular of the hands/wrists. Those patients presenting with hand/wrist arthralgia had significantly higher ferritin levels than patients without this joint involvement (p = 0.0005 for males and p < 0.0001 for females). After the introduction of the HFE genetic test an earlier diagnosis after first onset of hemochromatosis-associated clinical features was observed between 2006 and 2009 vs. 2000-2005 p = 0.01). CONCLUSIONS: Arthralgia, in particular of the hands/wrists, is a hallmark of hereditary hemochromatosis and its presence is associated with higher ferritin levels. Despite the availability of a genetic test, it often takes more than 6 years from the first onset of clinical features to diagnose hereditary hemochromatosis. This underlines the importance of raising the awareness of hemochromatosis and its typical clinical presentations. PMID- 22674402 TI - Twenty-five years of deep brain stimulation: celebrations and apprehensions. AB - The year 2012 marks the 25th anniversary of the birth of modern deep brain stimulation (DBS), which was introduced by Benabid et al in 1987, initially to treat tremor with DBS of the ventral intermediate nucleus of the thalamus. The subsequent extension of DBS to the subthalamic nucleus (STN), demonstrating its efficacy on virtually all symptoms of advanced Parkinson's disease (PD), sparked an era of intense clinical and research activities, eventually transcending PD and movement disorders to encompass mood and mind. Investigations of the role of DBS in a variety of neurological, psychiatric, cognitive, and behavioral conditions is ongoing. Serendipitous discoveries and advances in functional imaging are providing "new" brain targets for an increasing number of pathologies. Toward the end of this quarter of a century of DBS, there have been some indications that the field may be at risk of gliding down a slippery slope, reminiscent of the excesses of the old-era DBS. Although there are many reasons this year to celebrate the achievements of 25 years of modern DBS, there are also reasons to fear the opening of a new Pandora's box. PMID- 22674403 TI - Preoperative evaluation and management of the pancreatic head mass. AB - The differential diagnosis of a pancreatic head mass encompasses a wide range of clinical entities that include both solid and cystic lesions. This chapter focuses on our approach to the patient presenting with a newly found pancreatic head mass with the main goals of determining the risk of the lesion being malignant or premalignant, resectability if the patient is appropriate for surgical intervention, assessment of need for multimodality treatment and determination the patient's surgical risk. PMID- 22674404 TI - A longitudinal study of pain variability and its correlates in ambulatory patients with advanced stage cancer. AB - BACKGROUND: Although pain is common among patients with advanced cancer, little is known about longitudinal variability in pain intensity. For this report, the authors examined variability in pain intensity over 24 months among ambulatory patients with advanced stage cancers, associations between patient characteristics and within-patient pain variability, and the relation of pain variability to overall survival. METHODS: The sample comprised 949 patients with solid tumors who received care and reported pain scores in at least 3 different months within 24 months of their initial stage IV diagnosis during the period from 2004 to 2006. Pain intensity was measured using a scale ranging from 0 (no pain) to 10 (worst pain). Pain variability was defined as the standard deviation of the maximum monthly pain scores and was dichotomized at the 50th percentile into high and low variability groups. RESULTS: Considerable between-patient differences in pain variability (range, 0-5.77) were observed. Nonwhites, patients with a stage IV cancer diagnosed within the previous 3 months, and those with moderate or severe pain at baseline were more likely to experience high pain variability. Although patients with head and neck cancer generally had the highest pain variability, the intensity of their pain typically decreased over the disease course. High pain variability with worsening pain trajectory was associated with increased risk of death. CONCLUSIONS: Longitudinally, pain intensity was highly variable among patients with stage IV cancer. Minority patients, newly diagnosed patients, patients with head and neck cancer, and patients with moderate or severe pain at baseline were at higher risk of large fluctuations in pain intensity. PMID- 22674405 TI - Low-level laser therapy in collagenase-induced Achilles tendinitis in rats: analyses of biochemical and biomechanical aspects. AB - NSAIDs are widely prescribed and used over the years to treat tendon injuries despite its well-known long-term side effects. In the last years several animal and human trials have shown that low-level laser therapy (LLLT) presents modulatory effects on inflammatory markers, however the mechanisms involved are not fully understood. The aim of this study was to evaluate the short-term effects of LLLT or sodium diclofenac treatments on biochemical markers and biomechanical properties of inflamed Achilles tendons. Wistar rats Achilles tendons (n = 6/group) were injected with saline (control) or collagenase at peritendinous area of Achilles tendons. After 1 h animals were treated with two different doses of LLLT (810 nm, 1 and 3 J) at the sites of the injections, or with intramuscular sodium diclofenac. Regarding biochemical analyses, LLLT significantly decreased (p < 0.05) COX-2, TNF-alpha, MMP-3, MMP-9, and MMP-13 gene expression, as well as prostaglandin E(2) (PGE(2) ) production when compared to collagenase group. Interestingly, diclofenac treatment only decreased PGE(2) levels. Biomechanical properties were preserved in the laser-treated groups when compared to collagenase and diclofenac groups. We conclude that LLLT was able to reduce tendon inflammation and to preserve tendon resistance and elasticity. PMID- 22674406 TI - A quantum chemical calculation on Fe(CO)5 revealing the operation of the Dewar Chatt-Duncanson model. AB - A nonstandard computational scheme has been applied to calculate Fe(CO)(5) with the aim to illustrate the operation of the Dewar-Chatt-Duncanson model by computation. A full configuration interaction (CI) calculation in an active space has been performed. The active space is built from naturally localized molecular orbitals (NLMOs) localized in bond regions or forming lone pairs. For selecting this active space, Weinhold's perturbation theory formulated in the natural bond orbital (NBO) space has been applied. Bonding, lone pair, and antibond NBOs exhibiting large interaction energies serve to define the active space. The actually applied active space, however, comprises NLMOs that are close in shape to the NBOs indicated by perturbation theory. Thus, a CI calculation with localized orbitals has been performed meeting the classical reasoning of chemists that is often based on local bonding concepts. The computational scheme yields the Lewis structure for Fe(CO)(5) whose energy is identical to the Hartree-Fock energy. The Lewis energy comprises CO -> Fe sigma-electron transfer (ET) and CO < Fe electron back donation (BD). This Lewis energy gets lowered by localized correlation energy contributions caused by ET processes where electrons are back donated from the Fe d-lone pairs into the CO ligands. Thus, electron correlation within the selected active space is dominated by electron BD. Energies and electron populations of the NBOs support the notion that electrons are preferentially back donated into the equatorial CO ligands. Weights of local Slater determinants, determining the correlation energy, also point to a predominant BD into the equatorial CO ligands. Correlation energy increments resulting from electron BD into single antibond orbitals of the CO ligands have been calculated. These energy quantities also demonstrate that BD into the equatorial CO ligands is more energy lowering than BD into the axial CO ligands. PMID- 22674408 TI - Serum surfactant protein D: biomarker of chronic obstructive pulmonary disease. AB - BACKGROUND: Surfactant protein D (SP-D) is a lung-specific protein proposed to predict clinical outcomes in patients with chronic obstructive pulmonary disease (COPD). However, the changes in serum SP-D during acute exacerbation (AECOPD) episodes and the relationship of serum SP-D with the overall severity of the disease in stable COPD (SCOPD) remain unclear. METHODS: Serum SP-D levels were analyzed in three groups, including AECOPD (n=40), SCOPD (n=71), and controls (n=60). In AECOPD group, serum SP-D levels were determined at 1, 5, 14, and 30 days post-exacerbation. In SCOPD group, BODE (body mass index, airflow obstruction, dyspnea, exercise capacity) index was evaluated for severity assessment. RESULTS: Serum SP-D levels were sequentially elevated from the controls to the SCOPD, and then to the AECOPD (p< 0.001). During an AECOPD episode, the raised serum SP-D levels subsided at day 5 (p> 0.05), fell markedly at day 14 (p< 0.001), and continued to decline at day 30 (p< 0.001). Among patients with SCOPD, serum SP-D levels correlated positively with the BODE index (p< 0.01). CONCLUSIONS: The longitudinal changes in serum SP-D levels during an AECOPD episode suggest that SP-D may be a potential systemic biomarker for COPD exacerbation. The correlation of serum SP-D levels with the BODE index suggests that circulating SP-Ds can reflect the overall severity of SCOPD. PMID- 22674409 TI - Elevated IL-1alpha and CXCL10 serum levels occur in patients with homozygous sickle cell disease and a history of acute splenic sequestration. AB - Acute splenic sequestration (ASS) and chronic hypersplenism are common features of homozygous sickle cell (SS) disease in the first 5 years of life affecting one third of subjects in the Jamaican Cohort Study. The risk factors are largely unknown and the current study explores a possible role of genetic factors. We have explored these in subjects who received splenectomy in the management of ASS (n=8) or chronic hypersplenism (n=9) along with age, gender, and genotype matched controls using Luminex Technology to assess 42 human cytokines/chemokines, including IL-1alpha and CXCL10 (IP-10). Levels of IL-1alpha (p=0.008) and CXCL10 (p=0.009) were significantly elevated in patients treated by splenectomy compared with the control group. Levels of IL-1alpha were significantly higher in those with a history of ASS compared with matched normal controls (p=0.028) but not in those treated for hypersplenism (p=0.093). Furthermore, several significant differences were found in the median ratios of some cytokine biomarkers between the splenectomized group and the normal controls. These observations are consistent with acute splenic sequestration having a distinct phenotype which may be helpful in predicting those at risk of this complication and suggest that the mechanism of these differences merit further study. PMID- 22674407 TI - HuR inhibits apoptosis by amplifying Akt signaling through a positive feedback loop. AB - Human antigen R (HuR) is a post-transcriptional regulator of gene expression that plays a key role in stabilizing mRNAs during cellular stress, leading to enhanced survival. HuR expression is tightly regulated through multiple transcription and post-transcriptional controls. Although HuR is known to stabilize a subset of mRNAs involved in cell survival, its role in the survival pathway of PI3 kinase/Akt signaling is unclear. Here, we show that in renal proximal tubule cells, HuR performs a central role in cell survival by amplifying Akt signaling in a positive feedback loop. Key to this feedback loop is HuR-mediated stabilization of mRNA encoding Grb10, an adaptor protein whose expression is critical for Akt activation. Stimulation of Akt by interaction with Grb10 then activates NF-kappaB, which further enhances HuR mRNA and protein expression. This feedback loop is active in unstressed cells, but its effects are increased during stress. Therefore, this study demonstrates a central role for HuR in Akt signaling and reveals a mechanism by which modest changes in HuR levels below or above normal may be amplified, potentially resulting in cell death or cellular transformation. PMID- 22674410 TI - Association of the wild-type A/A genotype of MBL2 codon 54 with asthma in a North Indian population. AB - BACKGROUND: High serum MBL level as well as polymorphisms in the mannose-binding lectin 2 (MBL2) gene resulting in MBL deficiency are involved in the mechanism of a number of non-infectious diseases such as asthma, conferring either risk or protection in different population studies. MBL being the first reactant of the MBL pathway is also a major determinant of the fate of the anaphylatoxins such as C3a and C5a, which are also pro-inflammatory mediators. The MBL2 gene polymorphisms thus control the serum levels of MBL as well as C3a and C5a. OBJECTIVE: This is the first case-control study conducted in India, investigating the role of MBL2 codon 54 A/B polymorphism in asthma pathogenesis. METHODS: A case-control study was performed with a total of 992 adult subjects, including 410 adult asthmatics and 582 healthy controls from regions of North India. The MBL2 codon 54 A/B polymorphism was genotyped by PCR-RFLP. RESULTS: Statistical analysis for the codon 54 polymorphism revealed that the wild (A) allele was significantly associated with asthma with OR=1.9, 95% CI (1.4-2.4), and p< 0.001. CONCLUSION: The MBL2 codon 54 A/B polymorphism is significantly associated with asthma and its phenotypic traits as the wild (A/A) genotype confers a significant risk towards the disease in the studied North Indian population. PMID- 22674411 TI - Plasma seprase and DPP4 levels as markers of disease and prognosis in cancer. AB - Seprase (fibroblast activation protein alpha) has been examined as an invasion biomarker for various types of solid tumors. We studied whether plasma levels of seprase and homologous protease, DPP4 in cancer might serve as tumor biomarkers. We developed sensitive and specific Enzyme-Linked Immunosorbent Assays (ELISAs) to measure these proteases. In 747 plasma samples (from 139 healthy volunteers and 561 cancer patients), mean seprase and DPP4 levels were 0.51 +/- 0.30 and 4.65 +/- 6.37 MUg/mL, respectively, and they were correlated with each other (R(2) = 0.382). Plasma DPP4 and seprase levels were significantly lower in cancer patients compared with healthy subjects (4.38 versus 5.65 MUg/mL, p< 0.001 for DPP4; 0.46 versus 0.66 MUg/mL, p< 0.001 for seprase). Higher DPP4 was associated with better survival in all cancers combined (n=346) as well as in head and neck malignancies (n=38). Higher seprase was associated with better survival in all non-metastatic cancers combined (n=151) as well as head and neck malignancies, but worse survival in colorectal cancers (n=47). This study demonstrates that in contrast to the high expression in solid tumors, plasma concentrations of seprase and DPP4 are reduced and correlate inversely with survival in most types of cancer, suggesting that these circulating proteases represent useful tumor markers. PMID- 22674412 TI - Abnormal expression of matrix metalloproteinase-9 (MMP9) correlates with clinical course in Chinese patients with endometrial cancer. AB - AIMS AND BACKGROUND: The aim of the present study was to analyze the expression of matrix metalloproteinase-9 (MMP9) in endometrial cancer and its correlation with clinicopathologic features in Chinese patients, including the survival of patients with endometrial cancer. METHODS: Using immunohistochemistry analysis, we analyzed MMP9 protein expression in clinicopathologically characterized 128 endometrial cancer (EC) cases with age ranging from 30 to 85 years (median=51.6 years) and 30 endometrial atypical hyperplasia (EAH) and 30 normal endometrium (NE). Cases with greater than or equal to 6 and less than 6 with the score value of cytoplasmic MMP9 immunostaining were regarded as high expression and low expression, respectively. The relationship between the expression levels of MMP9 and clinical features was analyzed in EC cases. RESULTS: Immunohistochemical analysis revealed that the protein expression of MMP9 detected in EC tissues was higher than that in the EAH tissues and NE tissues (P=0.006). In addition, high levels of MMP9 protein were positively correlated with the status of lymph node metastasis (P=0.044) and the histopathological grade (P<0.05) of EC patients. Patients with higher MMP9 expression did not correlate with EC patients' clinical outcome in China. Multivariate analysis suggested that status of lymph node metastasis and depth of myometrial invasion, but not MMP9 expression level, were significantly correlated with patients' survival. CONCLUSION: MMP9 is highly expressed in ECs and correlates with the progression of ECs, but not be helpful in predicting the prognosis of EC patients. PMID- 22674413 TI - Eicosanoids in exhaled breath condensate and bronchoalveolar lavage fluid of patients with primary lung cancer. AB - Although eicosanoids are involved in lung carcinogenesis they were poorly investigated in exhaled breath condensate (EBC) and bronchoalveolar lavage fluid (BALf) in patients with primary lung cancer. In this study 17 patients with diagnosed non-small cell lung cancer, 10 healthy smokers and 12 healthy nonsmokers were included. The levels of cys-LTs, 8-isoprostane, LTB4 and PGE2 were measured before any treatment in the EBC of all patients and in BALf of patients with lung cancer by enzyme linked immunosorbent assay. 8-isoprostane, LTB4, cys-LTs and PGE2 were detectable in the EBC and BALf. There were no significant differences between healthy smokers and nonsmokers in concentrations of all measured mediators. Compared with both healthy controls, patients with diagnosed lung cancer displayed higher concentrations of cys-LTs (p< 0.05) and LTB4 (p < 0.05) in EBC. In patients with lung cancer, the mean concentrations of all measured mediators were significantly higher in BALf compared with EBC and there was a significant, positive correlation between concentration of cys-LTs, LTB(4) and 8-isoprostane in BALf and their concentrations in the EBC (r=0.64, p < 0.05, r=0.59, p< 0.05, r=0.53, p< 0.05 respectively). Since cys-LT, LTB4 and 8 isoprostane concentrations in EBC from patients with lung cancer reflect their concentrations in BALf, they may serve as a possible non-invasive method to monitor the disease and to assess the effectiveness of therapy. PMID- 22674415 TI - Method to assemble and integrate biochemical pathways into the chloroplast genome of Chlamydomonas reinhardtii. AB - Recombinant protein expression in the chloroplasts of green algae has recently become more routine; however, the heterologous expression of multiple proteins or complete biosynthetic pathways remains a significant challenge. Here, we show that a modified DNA Assembler approach can be used to rapidly assemble multiple gene biosynthetic pathways in yeast and then integrate these assembled pathways at a site-specific location in the chloroplast genome of the microalgal species Chlamydomonas reinhardtii. As a proof of concept, this method was used to successfully integrate and functionally express up to three reporter proteins (AphA6, AadA, and GFP) in the chloroplast of C. reinhardtii. An analysis of the relative gene expression of the engineered strains showed significant differences in the mRNA expression levels of the reporter genes and thus highlights the importance of proper promoter/untranslated region selection when constructing a target pathway. This new method represents a useful genetic tool in the construction and integration of complex biochemical pathways into the chloroplast genome of microalgae and should aid current efforts to engineer algae for biofuels production and other desirable natural products. PMID- 22674414 TI - Expression of HLA-B27 causes loss of migratory dendritic cells in a rat model of spondylarthritis. AB - OBJECTIVE: In rats transgenic for human HLA-B27 and beta(2) -microglobulin (B27 transgenic rats), colitis and peripheral inflammation develop spontaneously. Therefore, B27-transgenic rats provide a model of spondylarthritis. Because inflammation in these rats requires CD4+ T lymphocytes and involves intestinal pathology, we hypothesized that dendritic cells (DCs) that migrate from the intestine and control CD4+ T cell differentiation would be aberrant in B27 transgenic rats. METHODS: Migrating intestinal lymph DCs were collected via thoracic duct cannulation from B27-transgenic and control (HLA-B7-transgenic or nontransgenic) rats. The phenotypes of these DCs and of mesenteric lymph node DCs were assessed by flow cytometry. The ability of DCs to differentiate from bone marrow precursors in vitro was also assessed. RESULTS: Lymph DCs showed increased activation and, strikingly, lacked the specific DC population that is important for maintaining tolerance to self-antigens. This population of DCs was also depleted from the mesenteric lymph nodes of B27-transgenic rats. Furthermore, in vitro culture of DCs from bone marrow precursors revealed a defect in the ability of B27-transgenic rats to produce DCs of the migratory phenotype, although the DCs that were generated induced enhanced interleukin-17 (IL-17) production from naive CD4+ T cells. CONCLUSION: We describe 2 different mechanisms by which HLA B27 may contribute to inflammatory disease: increased apoptotic death of B27 transgenic DCs that normally function to maintain immunologic tolerance and enhanced IL-17 production from CD4+ T cells stimulated by the surviving B27 transgenic DCs. PMID- 22674416 TI - Development and evaluation of a dot blot assay for rapid determination of invasion-associated gene ibeA directly in fresh bacteria cultures of E. coli. AB - The ibeA gene, one of the important invasion-associated genes in neonatal meningitis Escherichia coli (NMEC), has been recently detected in avian pathogenic E. coli (APEC). Thus, it is necessary to close monitor the possible contamination of the poultry farms and its products to people. Here, a dot blot method for detecting the ibeA gene in E. coli was developed and validated. For the present study, probe sequence was designed and optimized for the specificity of dot blot. A 342-bp conserved fragment of ibeA gene was selected and labeled with digoxigenin (DIG)-dUTP according to the manufacturer's guidelines, which indicated that this probe hybridizes with ibeA. In our established method, the bacteria culture samples were directly spotted on the membrane, following simple lyses on the membrane. Hence, the extraction of genomic DNA is not required, which reduces the workload and shortens the time. Furthermore, this assay was very sensitive, which could detect as few as 2.5 * 10(3) CFU bacteria. The diagnostic reliability of this dot blot was evaluated on 467 APEC bacteria samples by using PCR analysis. Both methods showed that the result was in complete concordance. The dot blot assay was proved to be a simple, rapid, highly accurate, and cost-effective method to identify invasion-associated genes ibeA, which could be applied for initial screening of a large number of clinical samples or direct detection of bacteria culture. PMID- 22674417 TI - Expression of ferritin-like protein in Listeria monocytogenes after cold and freezing stress. AB - The cold shock protein family consists of the transfer of the foodborne pathogen Listeria monocytogenes from 37 to 4 and -20 degrees C and was characterized by the sharp induction of a low molecular mass protein. This major cold shock protein ferritin-like protein (Flp) has an important role in regulation of various microbial physiological processes. Flp have a molecular mass of about 18 kDa, as observed on SDS-PAGE. The purification procedure including ammonium sulfate fractionation was used. Monospecific polyclonal antibodies raised in rabbits against the purified new Flp immunostained a single 18-kDa Flp band in extracts from different cytoplasmic proteins blotted onto nitrocellulose. A 411 bp cDNA fragment that corresponds to an internal region of an flp gene was obtained by RT-PCR. Our result indicated a surexpression of major cold shock protein and an important increase in flp mRNA amount after a downshift temperature especially at -20 degrees C. PMID- 22674418 TI - Threats to patient safety in the primary care office: concerns of physicians and nurses. AB - BACKGROUND: Little is known about primary care professionals' concerns about risks to patient safety. AIM: To identify threats to patient safety in the primary care office from the perspective of physicians and nurses. DESIGN: Cross sectional survey; participants were asked to name and rank threats to safety they personally were most concerned about. SETTING: Physicians and nurses working in primary care offices in Switzerland. METHODS: Verbatim reports were analysed under an inductive content-analysis framework. Coded threats were quantitatively analysed in terms of frequency and prioritisation. Differences between physicians and nurses were analysed. RESULTS: Of 1260 invited individuals, 630 responded to the survey and 391 (31%) described 936 threats to patient safety. The coding system included 29 categories organised in 5 themes. Agreement of coders was good (kappa = 0.87, CI = 0.86-0.87). Safety of medication (8.8%), triage by nurses (7.2%) and drug interactions (6.8%) were the threats cited most frequently. Errors in diagnosis (OR = 0.21, CI 0.09-0.47, p <0.001), drug interactions (OR = 0.10, CI 0.04-0.25, p <0.001) and compliance of patients (OR = 0.28, CI 0.08 0.96, p = 0.044) were more likely to be cited by physicians. X-rays (OR = 3.34, CI 1.04-10.71, p = 0.043), confusion of patients or records (OR = 3.28, CI 1.55 6.94, p = 0.002), hygiene (OR = 3.21, CI1.12-9.19, p = 0.030), safety of office rooms (OR = 6.70, CI 1.46-30.73, p = 0.014), and confidentiality (OR = 7.38, CI 1.63-33.50, p = 0.010) were more likely to be described by nurses. CONCLUSION: Physicians and nurses are concerned about diverse threats to patient safety in primary care. Involving both groups in detection and analysis of risks in medical offices seems a valuable strategy to improve collaboration and safety. PMID- 22674419 TI - NDR1/STK38 potentiates NF-kappaB activation by its kinase activity. AB - Human NDR1/STK38 belongs to the nuclear-Dbf2-related (NDR) family of Ser/Thr kinases. It has been implicated to function in centrosome duplication, control of cell cycle and apoptosis. However, the mechanism of NDR1 signaling pathway remains largely elusive. Here, we report a novel role of NDR1 in NF-kappaB activation. By overexpression, NDR1 potentiates NF-kappaB activation induced by TNFalpha, whereas knockdown of NDR1 expression inhibits NF-kappaB activation induced by TNFalpha. Coimmunoprecipitation shows that NDR1 interacts with multiple signal components except p65 in NF-kappaB signaling pathway. Furthermore, both phosphorylation and kinase dead mutants of NDR1 lose their synergistic effects on TNFalpha-induced NF-kappaB activation. siRNA oligo against NDR1 and kinase dead mutant as well mainly block the NF-kappaB activation induced by TRAF2 but not RIP1. Furthermore, kinase dead mutant of NDR1 fails to interact with TRAF2. Taken together, our findings suggest an unknown function of NDR1, which may regulate NF-kappaB activation by its kinase activity. PMID- 22674420 TI - Predictive model for spontaneous preterm labor among pregnant women with contractions and intact amniotic membranes. AB - PURPOSE: To determine a predictive model for supporting decisions relating to the prognosis for women presenting with preterm labor and intact membranes. METHOD: We conducted a prospective observational cohort study on 70 pregnant women at between 22 and 34 weeks of gestation. Transvaginal sonographic evaluation on the cervix was performed once on women who had completed a course of parenteral tocolysis. The sonographic parameters of cervical length measurement and presence of cervical glandular area were obtained. The outcome variable was occurrences of preterm delivery (<35 weeks). Using a univariate logistic regression model, the coefficients of each independent variable were first estimated. To construct the predictive model, multivariate logistic regression containing all the selected variables that might be related to preterm delivery was used as the starting point. Accuracy, sensitivity, specificity and predictive values were used to measure associations of predicted probabilities and to check the ability of the model to predict outcomes. The predictive analyses were based on logistic regression models, with calculation of odds ratios and 95 % confidence intervals. RESULTS: The incidence of preterm delivery was 32.80 % (23/70). After validation, the predictive model proposed showed accuracy of 87.88 %, sensitivity of 78.26 % and specificity of 93.02 %. CONCLUSION: The model presented good accuracy with correspondence between predictions and observations, and has the capacity to become a useful tool for management of pregnant women with preterm labor and intact amniotic membranes. PMID- 22674421 TI - Development of a differential suction electrode for improved intravaginal recordings of pelvic floor muscle activity: reliability and motion artifact assessment. AB - AIM: The purposes of this study were to compare: (i) the reliability of electromyography (EMG) activity recorded from the pelvic floor muscles (PFMs) using a new differential suction electrode (DSE) to the reliability of EMG data recorded using other common electrodes, and (ii) motion artifact contamination of EMG activity recorded from the PFMs using the DSE and the FemiscanTM electrode. METHODS: With the DSE and the FemiscanTM in situ, at two separate sessions, each of 20 participants performed three repetitions of a maximum voluntary contraction (MVC) of their PFMs, and 10 repetitions of a maximal effort cough. With Delsys(r) electrodes located over the biceps brachii, each participant performed three repetitions of a MVC. Between-trial and between-day reliability were assessed using several methods. Motion artifact was assessed by comparing the proportion of contaminated files recorded by each electrode during coughing. RESULT: The DSE was found to have excellent between-trial reliability, as were the FemiscanTM and Delsys(r) electrodes. Between-day reliability was good for the DSE, but reliability was higher for the Delsys(r) electrode and the FemiscanTM electrode. The DSE performed better than the FemiscanTM electrode in terms of motion artifact contamination. CONCLUSIONS: The DSE has excellent between-trial reliability and performs better than the FemiscanTM electrode in terms of motion artifact contamination. It does not perform as well as the FemiscanTM electrode in terms of between-day reliability--a result that is not unexpected given the localized region from which the DSE records activity. PMID- 22674422 TI - Ion-exchange-assisted synthesis of Pt-VC nanoparticles loaded on graphitized carbon: a high-performance nanocomposite electrocatalyst for oxygen-reduction reactions. AB - Carbide-based electrocatalysts are superior to traditional carbon-based electrocatalysts, such as the commercial Pt/C electrocatalysts, in terms of their mass activity and stability. Herein, we report a general approach for the preparation of a nanocomposite electrocatalyst of platinum and vanadium carbide nanoparticles that are loaded onto graphitized carbon. The nanocomposite, which was prepared in a localized and controlled fashion by using an ion-exchange process, was an effective electrocatalyst for the oxygen-reduction reaction (ORR). Both the stability and the durability of the Pt-VC/GC nanocomposite catalyst could be enhanced compared with the state-of-the-art Pt/C. This approach can be extended to the synthesis of other metal-carbide-based nanocatalysts. Moreover, this straightforward synthesis of high-performance composite nanocatalysts can be scaled up to meet the requirements for mass production. PMID- 22674423 TI - A multi-institution experience comparing the clinical and physiologic differences between upper extremity and lower extremity melphalan-based isolated limb infusion. AB - BACKGROUND: Although studies of melphalan-based isolated limb infusion (ILI) combine data from upper extremity (UE) treatments with those from lower extremity (LE) treatments, differences between the 2 may be clinically important. METHODS: Candidates for UE ILI (n = 51) and LE ILI (n = 192) were identified from prospective databases at 2 institutions. The Response Evaluation Criteria in Solid Tumors and Wieberdink toxicity scale were used as appropriate. RESULTS: The following patients had indications for UE ILI: melanoma, 36 of 47 patients (77%); sarcoma, 5 of 47 patients (11%); Merkel cell sarcoma, 3 of 47 patients (6%), and squamous cell carcinoma, 3 of 47 patients (6%). The patients who underwent UE ILI, as expected, had lower limb volumes (mean, 2.5 L vs 8.6 L; P < .001) and lower mean melphalan doses (20.7 mg vs 49.5 mg; P < .001). On perfusate blood gas analysis, the mean base excess at 30 minutes (-13.9 vs -9.1; P < .001) and the mean pH at 30 minutes (7.06 vs 7.15; P < .001) were lower for UE procedures than for LE procedures, although the mean ischemic time was longer in LE procedures (67.2 minutes) than in UE procedures (61.6 minutes; P = .03). The rate of regional toxicity grade >=3 for UE ILI was 7% compared with 24% (P = .005) for LE ILI. There was no difference in the complete response rate for melanoma UE procedures (28%; 95% confidence interval, 16%-44%) compared with LE ILI procedures (32%; 95% confidence interval, 25%-39%). CONCLUSIONS: ILI for UE disease was associated with similar complete response rates but lower toxicity than ILI for LE disease and with different physiologic sequelae despite comparable methods. The UE appears relatively resistant to toxic effects of melphalan-based ILI as currently performed, which suggests a potential for further optimization of drug dosing for UE ILI. PMID- 22674424 TI - The platelet count in EDTA-anticoagulated blood from patients with thrombocytopenia may be underestimated when measured in routine laboratories. AB - Spuriously low platelet counts (PCs) can be observed in normal blood samples anticoagulated with ethylenediamine tetra-acetic acid (EDTA)and, much less frequently, with citrate-tris-pyridossalphosphate (CPT),due to time-dependent in vitro platelet agglutination. Accuracy in PC determination is essential as PC is one of the parameters that usually guides treatment for thrombocytopenic patients. PCs of 93 thrombocy to penic patients were measured in EDTA- or CPT anticoagulated blood samples immediately after sampling (t0) and 90 min (t90) after storage at room temperature. The presence of platelet agglutinates in blood samples was determined by examining blood smears using optical microscopy.PCs decreased at t90 with both anticoagulants. Platelet agglutinates were present at t90 in 27% of EDTA-samples vs. 2% of CPT-samples with decreased PCs (P < 0.001). Based on PCs in EDTA-samples, 15 patients (16%) shifted from a lower bleeding risk at t0 to a higher bleeding risk category at t90 (P 5 0.019), compared to 5 (5%) patients, based on PCs in CPT-samples. Therefore, time-dependent in vitro platelet agglutination in EDTA-blood samples may cause underestimation of PCs in thrombocytopenic patients, possibly leading to improper management. PMID- 22674427 TI - Erythropoietin-activated ERK/MAP kinase enhances GATA-4 acetylation via phosphorylation of serine 261 of GATA-4. AB - GATA-4, a zinc finger transcription factor, plays a critical role in heart development. Previous studies have shown that p300-targeted GATA-4 acetylation increases GATA-4 stability and transcriptional activity, which then stimulates hypertrophy of cardiomyocyte. Erythropoietin (EPO), an essential hypoxia-induced hormone for normal erythropoiesis, is known to exert cardioprotective effects against heart disease of either ischemic or non-ischemic origins. Although, various action mechanisms of EPO have been proposed in the diseased heart, its action mechanism in normal condition has not been investigated. In this study, we aimed to investigate the influence of EPO-induced ERK signaling on the regulation of GATA-4 protein action. EPO treatment increased the protein level of endogenous GATA-4 via ERK signaling pathway. Inhibition of ERK activity by U0126, suppressed EPO-induced expression of GATA-4 protein in rat cardiac myocytes. In addition, ERK activation by over-expression of constitutively active MEK1 strongly increased GATA-4 phosphorylation and subsequently enhanced its acetylation in P19 cells. EPO-induced ERK activation further increased the association of GATA-4 with p300. On the other hand, knock-down of p300 using siRNA diminished ERK induced GATA-4 acetylation. As EPO-induced GATA-4 phosphorylation via ERK signaling pathway directly correlated with GATA-4 acetylation, we investigated to identify the ERK-dependent phosphorylation sites in GATA-4. Site-directed mutagenesis implicated that Ser-261 in GATA-4 played an important role for ERK mediated GATA-4 acetylation. Taken together, these results indicated that EPO induced ERK signaling activation increased GATA-4 phosphorylation and acetylation, partly via increase in the association between GATA-4 and p300, and these processes required the phosphorylation of GATA-4 at Ser-261 residue. PMID- 22674425 TI - Feasibility of measuring prostate perfusion with arterial spin labeling. AB - Prostate perfusion has the potential to become an important pathophysiological marker for the monitoring of disease progression or the assessment of the therapeutic response of prostate cancer. The feasibility of arterial spin labeling, an MRI approach for the measurement of perfusion without an exogenous contrast agent, is demonstrated in the prostate for the first time. Although various arterial spin labeling methods have been demonstrated previously in highly perfused organs, such as the brain and kidneys, the prospect of obtaining such measurements in the prostate is challenging because of the relatively low blood flow, long transit times, susceptibility-induced image distortion and local motion. However, despite these challenges, this study demonstrates that, with a whole-body transmit coil and external receiver array, global prostate perfusion can be measured with arterial spin labeling at 3 T. In five healthy subjects with a mean age of 44 years, the mean total prostate blood flow was measured to be 25.8 +/- 7.1 mL/100 cm(3) /min, with an estimated bolus duration and arterial transit time of 884 +/- 209 ms and 721 +/- 131 ms, respectively. PMID- 22674429 TI - [Abstracts of DEGRO 2012, THe 18th Annual Congress of the German Society for Radio-oncology. June 7-10, 2012. Wiesbaden, Germany]. PMID- 22674430 TI - [Abstracts of the 28th Annual Meeting of the Austrian Society for Radio-oncology, Radiobiology and Medical Radio-physics (OGRO 2011). November 17-19, 2011. Vienna, Austria]. PMID- 22674428 TI - Gyrate atrophy: clinical and genetic findings in a female without arginine restricted diet during her first 39 years of life and report of a new OAT gene mutation. AB - We report the clinical and genetic data obtained at a 17-year follow-up examination of a patient with gyrate atrophy, without an arginine-restricted diet. Patient examinations included visual acuity (VA), perimetry, biomicroscopy, funduscopy, fundus photography, fundus autofluorescence (FAF), spectral-domain optical coherence tomography (OCT), and standard full-field electroretinography (ERG). Blood samples were taken for measurement of serum ornithine level and molecular genetic analysis of the OAT gene. The female was 22 years of age when gyrate atrophy was diagnosed based on peripheral chorioretinal atrophy and an increased ornithine level. Reexamination after 17 years revealed a reduced VA (0.25 OU), dense cataract, extensive peripheral chorioretinal atrophy, a further increased ornithine level, but only slow progression of visual field constriction, and still detectable ERG amplitudes. FAF was absent in the atrophic periphery and almost homogeneous at the posterior pole except parafoveally. OCT showed interruption of the foveal inner/outer segment junction and parafoveal microcystoid spaces. After cataract surgery, VA increased to the same values as those found at the age of 22 years (0.5 OD, 0.6 OS). Molecular analysis revealed a new deletion c.532_536delTGGGG (p.Trp178X) and a known mutation c.897C>G (p.Tyr299X) in the OAT gene. Although the patient had refused to diet during her first 39 years of life, the gyrate atrophy showed a very slow progression. FAF allows evaluating the integrity of the retinal pigment epithelium and may help to delimit gyrate atrophy from choroideremia. Interruption of foveal inner/outer segment junction and cystoid macula edema appears in gyrate atrophy. PMID- 22674431 TI - Structural insights into catalysis by betaC-S lyase from Streptococcus anginosus. AB - Hydrogen sulfide (H(2)S) is a causative agent of oral malodor and may play an important role in the pathogenicity of oral bacteria such as Streptococcus anginosus. In this microorganism, H(2)S production is associated with betaC-S lyase (Lcd) encoded by lcd gene, which is a pyridoxal 5'-phosphate (PLP) dependent enzyme that catalyzes the alpha,beta-elimination of sulfur-containing amino acids. When Lcd acts on L-cysteine, H(2)S is produced along with pyruvate and ammonia. To understand the H(2)S-producing mechanism of Lcd in detail, we determined the crystal structures of substrate-free Lcd (internal aldimine form) and two reaction intermediate complexes (external aldimine and alpha aminoacrylate forms). The formation of intermediates induced little changes in the overall structure of the enzyme and in the active site residues, with the exception of Lys234, a PLP-binding residue. Structural and mutational analyses highlighted the importance of the active site residues Tyr60, Tyr119, and Arg365. In particular, Tyr119 forms a hydrogen bond with the side chain oxygen atom of L serine, a substrate analog, in the external aldimine form suggesting its role in the recognition of the sulfur atom of the true substrate (L-cysteine). Tyr119 also plays a role in fixing the PLP cofactor at the proper position during catalysis through binding with its side chain. Finally, we partly modified the catalytic mechanism known for cystalysin, a betaC-S lyase from Treponema denticola, and proposed an improved mechanism, which seems to be common to the betaC-S lyases from oral bacteria. PMID- 22674432 TI - Metabolic markers or conditions preceding Parkinson's disease: a case-control study. AB - Several metabolic markers or conditions have been explored as possible risk or protective factors for Parkinson's disease (PD); however, results remain conflicting. We further investigated these associations using a case-control study design. We used the medical records-linkage system of the Rochester Epidemiology Project to identify 196 subjects who developed PD in Olmsted County, Minnesota, from 1976 through 1995. Each incident case was matched by age (+/-1 year) and sex to a general population control. We reviewed the complete medical records of cases and controls in the medical records-linkage system to abstract information about body mass index (BMI), cholesterol level, hypertension, and diabetes mellitus preceding the onset of PD (or the index year). There were no significant differences between cases and controls for the metabolic markers or conditions investigated. No significant associations were found using 2 cutoffs for BMI level (BMI >= 25 or BMI >= 30 kg/m(2) ) and 3 cutoffs for cholesterol levels (>200, >250, or >300 mg/dL). Neither a diagnosis of hypertension or the documented use of antihypertensive medications was significantly associated with the subsequent risk of PD (odds ratio [OR], 1.00; 95% confidence interval [CI], 0.65-1.54; P = .99) nor was a diagnosis of diabetes mellitus or the use of glucose-lowering medications (OR, 0.77; 95% CI, 0.37-1.57; P = .47). Our study, based on historical information from a records-linkage system, does not support an association between BMI, cholesterol level, hypertension, or diabetes mellitus with later development of PD. PMID- 22674433 TI - Interaction of liposome-encapsulated cisplatin with biomolecules. AB - We prepared liposomes by hydrating 1,2-dioleoyl-sn-glycero-3-phosphocholine lipid with aqueous solutions of three "probe" molecules-cis diamminedichloroplatinum(II) (cis-[Pt(II)(NH(3))(2)Cl(2)], cisplatin), guanosine 5'-monophosphate (5'-GMP), and 9-ethylguanine (9-EtG)-in phosphate-buffered saline as well as N-(2-hydroxyethyl)piperazine-N'-ethanesulfonic acid buffer. The positively charged hydrolysis product of cisplatin, [Pt(II)(NH(3))(2)Cl(H(2)O)](+), is in the inner core of the liposomes and negatively charged 5'-GMP embeds in the lipid bilayer of liposomes. In the presence of cisplatin, the size of the liposomes remains unchanged, and for 5' GMP-embedded liposomes the size increases significantly compared with that of empty or control liposomes. In contrast, the neutral biomolecule 9-EtG was found to be dispersed in the exterior bulk water and the size of the liposomes remained the same as that of empty or control liposomes. When cisplatin-containing liposomes mix with 5'-GMP-embedded liposomes or liposomes with 9-EtG, the N7 nitrogen atom of 5'-GMP or 9-EtG binds the cisplatin, thus replacing the "leaving groups" and forming a bisadduct. After 48 h of mixing, the size of the liposomes changes for the mixture of 5'-GMP-embedded liposomes and cisplatin-containing liposomes. We used (1)H and (31)P NMR spectroscopic techniques to monitor incorporation or association of cisplatin and biomolecules with liposomes and their subsequent reactions with each other. The dynamic light scattering technique provided the size distribution of the liposomes in the presence and absence of probe molecules. PMID- 22674434 TI - Structures and free energy landscapes of aqueous zinc(II)-bound amyloid-beta(1 40) and zinc(II)-bound amyloid-beta(1-42) with dynamics. AB - Binding of divalent metal ions with intrinsically disordered fibrillogenic proteins, such as amyloid-beta (Abeta), influences the aggregation process and the severity of neurodegenerative diseases. The Abeta monomers and oligomers are the building blocks of the aggregates. In this work, we report the structures and free energy landscapes of the monomeric zinc(II)-bound Abeta40 (Zn:Abeta40) and zinc(II)-bound Abeta42 (Zn:Abeta42) intrinsically disordered fibrillogenic metallopeptides in an aqueous solution by utilizing an approach that employs first principles calculations and parallel tempering molecular dynamics simulations. The structural and thermodynamic properties, including the secondary and tertiary structures and conformational Gibbs free energies of these intrinsically disordered metallopeptide alloforms, are presented. The results show distinct differing characteristics for these metallopeptides. For example, prominent beta-sheet formation in the N-terminal region (Asp1, Arg5, and Tyr10) of Zn:Abeta40 is significantly decreased or lacking in Zn:Abeta42. Our findings indicate that blocking multiple reactive residues forming abundant beta-sheet structure located in the central hydrophobic core and C-terminal regions of Zn:Abeta42 via antibodies or small organic molecules might help to reduce the aggregation of Zn(II)-bound Abeta42. Furthermore, we find that helix formation increases but beta-sheet formation decreases in the C-terminal region upon Zn(II) binding to Abeta. This depressed beta-sheet formation in the C-terminal region (Gly33-Gly38) in monomeric Zn:Abeta42 might be linked to the formation of amorphous instead of fibrillar aggregates of Zn:Abeta42. PMID- 22674435 TI - Isolated limb perfusion with the tumor-targeting human monoclonal antibody cytokine fusion protein L19-TNF plus melphalan and mild hyperthermia in patients with locally advanced extremity melanoma. AB - BACKGROUND: L19-TNF is a tumor-targeting immunocytokine composed of the human L19 antibody binding to extra domain B (ED-B) of fibronectin of newly formed blood vessels, and of human TNF. This exploratory trial evaluates safety and clinical activity of L19-TNF plus melphalan-containing isolated limb perfusion (ILP) in extremity melanoma patients. METHODS: Seven and 10 patients received 325 ug and 650 ug of L19-TNF, respectively, during the ILP. Patients were studied for safety, tolerability, and clinical activity of this experimental L19-TNF ILP procedure. RESULTS: Non-hematologic toxicity of L19-TNF ILP was very low, but severe myelosuppression was seen in four patients. Although L19-TNF was administered at a TNF-equivalent dose of only 3.13 and 6.25% of the approved TNF (Beromun(r)) dose of 4 mg, L19-TNF ILP induced objective responses in 86 and 89% of patients, respectively, including a complete response (CR) in 5/10 patients treated with L19-TNF ILP at 650 ug that was durable at 12 months in four patients. No CR was seen at 325 ug of L19-TNF. CONCLUSIONS: ILP with L19-TNF had a favorable safety and a promising activity profile at a dose of 650 ug of L19 TNF, supporting the exploration of higher L19-TNF doses and a Phase II trial comparing L19-TNF ILP with standard melphalan-containing ILP. PMID- 22674437 TI - MicroRNA-199a-3p, microRNA-193b, and microRNA-320c are correlated to aging and regulate human cartilage metabolism. AB - MicroRNAs (miRNAs) are small RNAs of ~22 base pairs that regulate gene expression. We harvested cartilage tissue from patients with polydactylism, anterior cruciate ligament injury, and osteoarthritis undergoing total knee arthroplasty and used microarrays to identify miRNAs whose expression is upregulated or downregulated with age. The results were assessed by real-time PCR and MTT assay in a mimic group, in which synthetic double-stranded RNA from the isolated miRNA was transfected to upregulate expression, and in an inhibitor group, in which the miRNA was bound specifically to downregulate expression. The expression of two miRNAs (miR-199a-3p and miR-193b) was upregulated with age and that of one miRNA (miR-320c) was downregulated with age. A real-time PCR assay showed that type 2 collagen, aggrecan, and SOX9 expression were downregulated in the miR-199a-3p mimic group but was upregulated in the inhibitor group. Similar results were observed for miR-193b. By contrast, ADAMTS5 expression was downregulated in the miR-320c mimic group and upregulated in the inhibitor group. Cell proliferative activity was upregulated significantly in the miR-193b inhibitor group compared with the control group. We believe that miR-199a-3p and miR-193b are involved in the senescence of chondrocytes, and miR-320c is involved in the juvenile properties of chondrocytes. PMID- 22674439 TI - Re: Kojima Y, et al. Tamsulosin reduces nighttime urine production in benign prostatic hyperplasia patients with nocturnal polyuria: A prospective open-label long-term study using frequency-volume chart. Neurourol Urodyn 2012;31:80-85. PMID- 22674438 TI - An immunohistochemical signature comprising PTEN, MYC, and Ki67 predicts progression in prostate cancer patients receiving adjuvant docetaxel after prostatectomy. AB - BACKGROUND: Loss of the tumor suppressor PTEN is common in prostate cancer and may have prognostic significance. The authors examined PTEN and additional protein markers in primary tumors from patients with high-risk, localized prostate cancer who received adjuvant docetaxel in a prospective multicenter trial (TAX2501). METHODS: Fifty-six of 77 patients enrolled in TAX2501 had primary prostatectomy specimens available for immunohistochemical analysis of PTEN, MYC, ERG, tumor protein p53 (p53), antigen KI-67 (Ki67), and phosphorylated forms of Akt, mammalian target of rapamycin (mTOR), and S6 ribosomal protein. Protocol-defined progression included a prostate-specific antigen (PSA) level >= 0.4 ng/mL, radiologic/clinical recurrence, or death. Univariate and multivariable proportional hazards regression analyses were used to investigate the influence of PTEN status (and other protein markers) on progression-free survival (PFS). RESULTS: In this exploratory, post hoc analysis, PTEN protein loss (vs presence) was observed in 61% of patients and was associated with lower preoperative PSA levels, higher clinical stage, lower Ki67 expression, the presence of p53, and the presence of ERG. In univariate analysis, the factors associated with PFS included Gleason sum, seminal vesicle invasion, PTEN status, MYC expression, and Ki67 expression. In multivariable analysis, only 3 variables emerged as independent prognostic factors for PFS: PTEN status (P = .035), MYC expression (P = .001), and Ki67 expression (P < .001). A prognostic model was constructed that incorporated clinical covariates as well as information on PTEN, MYC, and Ki67. CONCLUSIONS: The current results indicated that PTEN status, MYC expression, and Ki67 expression in primary tumor samples may predict PFS more accurately than clinical factors alone in men with high-risk prostate cancer who receive adjuvant docetaxel after prostatectomy. If validated, these hypothesis-generating findings may have prognostic and therapeutic implications and may aid clinical trial design. PMID- 22674441 TI - [State of afairs and prospects of research in the health care professions]. PMID- 22674440 TI - Vascular smooth muscle cells remodel collagen matrices by long-distance action and anisotropic interaction. AB - While matrix remodeling plays a key role in vascular physiology and pathology, the underlying mechanisms have remained incompletely understood. We studied the remodeling of collagen matrices by individual vascular smooth muscle cells (SMCs), clusters and monolayers. In addition, we focused on the contribution of transglutaminase 2 (TG2), which plays an important role in the remodeling of small arteries. Single SMCs displaced fibers in collagen matrices at distances up to at least 300 MUm in the course of 8-12 h. This process involved both 'hauling up' of matrix by the cells and local matrix compaction at a distance from the cells, up to 200 MUm. This exceeded the distance over which cellular protrusions were active, implicating the involvement of secreted enzymes such as TG2. SMC isolated from TG2 KO mice still showed compaction, with changed dynamics and relaxation. The TG active site inhibitor L682777 blocked local compaction by wild type cells, strongly reducing the displacement of matrix towards the cells. At increasing cell density, cells cooperated to establish compaction. In a ring shaped collagen matrix, this resulted in preferential displacement in the radial direction, perpendicular to the cellular long axis. This process was unaffected by inhibition of TG2 cross-linking. These results show that SMCs are capable of matrix remodeling by prolonged, gradual compaction along their short axis. This process could add to the 3D organization and remodeling of blood vessels based on the orientation and contraction of SMCs. PMID- 22674442 TI - [Research in the health care professions]. PMID- 22674443 TI - [Research in the allied health professions: potentials for a needs-based health care in Germany]. PMID- 22674444 TI - [Recommendation]. PMID- 22674445 TI - Biologically produced nanosilver: current state and future perspectives. AB - Silver nanoparticles are one of the most commercialized nanomaterials. They are widely applied as biocides for their strong antimicrobial activity, but also their conductive, optic and catalytic properties make them wanted in many applications. The chemical and physical processes which are used to synthesize silver nanoparticles generally have many disadvantages and are not eco-friendly. In this review, we will discuss biological alternatives that have been developed using microorganisms or plants to produce biogenic silver. Until now, only their antimicrobial activity has been studied more into detail. In contrast, a wide range of practical applications as biocide, biosensor, and catalyst are still unexplored. The shape, size, and functionalization of the nanoparticles is defined by the biological system used to produce the nanoparticles, hence for every application a specific biological production process needs to be chosen. On the other hand, biogenic silver needs to compete with chemically produced nanosilver on the market. Large scale production generating inexpensive nanoparticles is needed. This can only be achieved when the biological production system is chosen in function of the yield. Hence, the true challenge for biogenic silver is finding the balance between scalability, price, and applicability. PMID- 22674446 TI - Pitfalls in statistical methods. PMID- 22674448 TI - Nanotransfer printing with sub-10 nm resolution realized using directed self assembly. AB - An extraordinarily facile sub-10 nm fabrication method using the synergic combination of nanotransfer printing and the directed self-assembly of block copolymers is introduced. The approach is realized by achieving the uniform self assembly of polydimethylsiloxane (PDMS)-containing block copolymers on a PDMS mold through the stabilization of the block copolymer thin films. This simple printing method can be applied on oxides, metals, polymers, and non-planar substrates without pretreatments. The fabrication of well-aligned metallic and polymeric functional nanostructures and crossed wire structures is also presented. PMID- 22674449 TI - [Renal replacement therapy for refractory heart failure]. AB - After broad cardiological and nephrological evaluation and consideration of optimal conservative options according to national and international guidelines, renal replacement therapy might be helpful in patients with refractory heart failure even if they are not dialysis-dependent. This is even more important as renal failure is a strong predictor for mortality in patients with severe congestive heart failure (CHF) and CHF is one of the fastest growing morbidities in western countries. Although peritoneal dialysis (PD) is frequently used in patients with CHF its role remains unclear. Acute chronic volume overload in refractory CHF is still an unresolved clinical problem. In patients with acute heart and renal failure with need of management in an intensive care unit, extracorporeal ultrafiltration or a dialysis modality should be preferred. In patients with chronic refractory CHF, volume overload and renal failure, peritoneal dialysis should be the therapy of choice. Due to the limited data available, treatment and outcome parameters should be recorded in the registry of the German Society of Nephrology (http://www.herz-niere.de). PMID- 22674450 TI - [A young woman with fulminant pulmonary embolism]. AB - We describe the case of a 24-year-old woman who was admitted to the emergency department with dyspnea and sinus tachycardia. The suspected diagnosis of pulmonary embolism was confirmed by computed tomography (CT) scan. The patient lost consciousness soon afterwards and was found to be pulseless. Cardiopulmonary resuscitation was performed and high dosis thrombolysis was given. The patient survived without sequelae and was discharged on oral anticoagulation from the hospital 8 days after the initial admission. In our opinion unknown factor-V Leiden in combination with a local form of hormonal contraception (NuvaRing(r)) was responsible for the deep venous thrombosis of the left leg and the pulmonary embolism. PMID- 22674451 TI - [Potentially inappropriate medication: the quality of pharmacotherapy in the elderly]. AB - Potentially inappropriate medication (PIM) in the elderly is a common problem in primary care. Depending on the setting under investigation, recent studies reported a prevalence of PIM up to 24% in Germany. In 2010 the German national PRISCUS list containing explicit criteria to identify PIM was published. First data show a possible association between PIM as defined by the Priscus list and negative health outcomes. However, prospective controlled trials are needed to assess whether interventions based on explicit criteria are able to improve patient-related outcome. Against this backdrop, the present review comments on recent data, especially those with impact for the German health care system. PMID- 22674452 TI - Computational study on hydrolysis of cefotaxime in gas phase and in aqueous solution. AB - We are presenting a theoretical study of the hydrolysis of a beta-lactam antibiotic in gas phase and in aqueous solution by means of hybrid quantum mechanics/molecular mechanics potentials. After exploring the potential energy surfaces at semiempirical and density functional theory (DFT) level, potentials of mean force have been computed for the reaction in solution with hybrid PM3/TIP3P calculations and corrections with the B3LYP and M06-2X functionals. Inclusion of the full molecule of the antibiotic, Cefotaxime, in the gas phase molecular model has been demonstrated to be crucial since its carboxylate group can activate a nucleophilic water molecule. Moreover, the flexibility of the substrate implies the existence of a huge number of possible conformers, some of them implying formation of intramolecular hydrogen bond interaction that can determine the energetics of the conformers defining the different states along the reaction profile. The results show PM3 provides results that are in qualitative agreement with DFT calculations. The free energy profiles show a step wise mechanism that is kinetically determined by the nucleophilic attack of a water molecule activated by the proton transfer to the carboxylate group of the substrate (the first step). However, since the main role of the beta-lactamase would be reducing the free energy barrier of the first step, and keeping in mind the barrier obtained from second intermediate to products, population of this second intermediate could be significant and consequently experimentally detected in beta-lactamases, as shown in the literature. PMID- 22674453 TI - Genetic characterization of mesenchymal, clear cell, and dedifferentiated chondrosarcoma. AB - Clear cell, mesenchymal, and dedifferentiated chondrosarcoma are rare, cartilaginous tumors with limited treatment options other than surgery. Conventional chondrosarcomas have been extensively studied at the genetic level, but for rare chondrosarcoma subtypes, this is merely restricted to case reports. Information on the genetics of rare chondrosarcomas may provide insight into the etiology of these specific disease subtypes and possible alternative treatment strategies. Therefore, the aim of this study was to genetically characterize this subset of rare tumors. Using array CGH, we gathered genomic information of 30 rare cartilaginous tumors. In addition, we constructed tissue microarrays with 2 mm cores of 23 clear cell, 23 mesenchymal, and 45 dedifferentiated chondrosarcomas, in triplicate. Using immunohistochemistry, we investigated expression of R132H IDH1, and p53 and retinoblastoma pathways. Results were verified and further investigated with a methylation assay and MLPA for CDKN2A/p16, and IDH1/2, and TP53 mutation analysis. Array-CGH showed numerous genomic alterations in all subtypes. However, only a limited number of recurrent alterations were detected, none of which seemed to be associated with the subtypes. The IDH1/2, p53, and retinoblastoma pathways were affected in 0, 9, and 95% of clear cell chondrosarcomas, in 0, 39, and 70% in mesenchymal chondrosarcomas, and in 50, 59, and 85% of dedifferentiated chondrosarcomas, respectively. Our results suggest an important role for the retinoblastoma pathway in all three rare chondrosarcoma subtypes investigated. PMID- 22674454 TI - Adolescent sexual victimization: a prospective study on risk factors for first time sexual assault. AB - The present study set out to investigate predictors of first time adolescent peer on-peer sexual victimization (APSV) among 238 female Grade 9 students from 30 schools in Denmark. A prospective research design was utilized to examine the relationship among five potential predictors as measured at baseline and first time APSV during a 6-month period. Data analysis was a binary logistic regression analysis. Number of sexual partners and displaying sexual risk behaviors significantly predicted subsequent first time peer-on-peer sexual victimization, whereas a history of child sexual abuse, early sexual onset and failing to signal sexual boundaries did not. The present study identifies specific risk factors for first time sexual victimization that are potentially changeable. Thus, the results may inform prevention initiatives targeting initial experiences of APSV. PMID- 22674455 TI - Geographic variation in utilization of sentinel lymph node biopsy for intermediate thickness cutaneous melanoma. AB - BACKGROUND AND OBJECTIVES: Sentinel lymph node biopsy (SLNB) is the standard for evaluation of the draining lymphatic basin for intermediate thickness melanoma. Despite this, SLNB has not been uniformly adopted. We hypothesized that there are geographic areas of the United States where patients are less likely to receive SLNB. METHODS: The Surveillance, Epidemiology, and End Results database was queried for patients who underwent surgery for intermediate thickness cutaneous melanoma (Breslow thickness 1.00-4.00 mm) from 2004 to 2008. Patients were categorized according to geographic area based on the reporting registry. Multivariate logistic regression models predicted use of SLNB. RESULTS: Entry criteria were met by 8957 patients. On multivariate analysis, patients from the South were less likely (OR 0.54, CI 0.48-0.62; P < 0.001) to receive a SLNB. Additional factors associated with a decreased likelihood of receiving a SLNB included head and neck primary tumor site, high or unknown serum LDH, Asian, Hispanic, Native American or unknown race, and increasing age. CONCLUSIONS: Patients from the South were less likely to receive a SLNB for an intermediate thickness cutaneous melanoma. This report of geographic disparities on a national level should be confirmed locally to better guide interventions aimed at eliminating these disparities. PMID- 22674456 TI - BMP induced inflammation: a comparison of rhBMP-7 and rhBMP-2. AB - Concern has been raised because of reports of inflammatory swelling following the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) and recombinant human bone morphogenetic protein-7 (rhBMP-7). The purpose of this study is to compare the inflammatory action of rhBMP-7 with those of rhBMP-2. ELISA assays (IL-6, TNF-alpha) were used to measure the cytokine response to different concentrations of rhBMP-7 and -2. Recombinant human BMP-7 was absorbed into absorbable collagen sponges and different amounts were implanted either subcutaneously (SC) or intramuscularly (IM) into the backs of rats. Using MRI and MIPAV software, we measured the degree of soft tissue edema at 3 h and at 2, 4, and 7 days postoperatively. After sacrificing rats on day 7 the inflammatory zone and mass were measured and the tissue examined histologically. Soft tissue edema after rhBMP-7 and rhBMP-2 implantation was dose-dependent and peaked at 3 h for the subcutaneous implants and at 2 days for the intramuscular implants. RhBMP-7 was associated with a significantly smaller soft tissue edema volume than was rhBMP-2 only at the highest dose (20 ug/ml). Both rhBMP-2 and rhBMP-7 triggered dose-dependent inflammatory reactions. Compared to rhBMP-2, rhBMP-7 is associated with somewhat smaller soft tissue edema volumes. Although rhBMP-7 is associated with an inflammatory reaction leading to soft tissue edema, at high doses this response is significantly less than that seen with rhBMP-2. Our animal model can be used to test materials that could ameliorate this reaction. PMID- 22674457 TI - Long-term safety profile of belimumab plus standard therapy in patients with systemic lupus erythematosus. AB - OBJECTIVE: To evaluate the safety profile of long-term belimumab therapy combined with standard therapy for systemic lupus erythematosus (SLE) in patients with active disease. METHODS: Patients who were randomized to receive intravenous placebo or belimumab 1, 4, or 10 mg/kg, plus standard therapy, and completed the initial 52-week double-blind treatment period were then allowed to enter a 24 week open-label extension phase. During the extension period, patients in the belimumab group either received the same dose or were switched to 10 mg/kg and patients in the placebo group were switched to belimumab 10 mg/kg. Patients who achieved a satisfactory response during the 24-week extension period were allowed to participate in the long-term continuation study of monthly belimumab 10 mg/kg. Adverse events (AEs) and abnormal laboratory results were analyzed per 100 patient-years in 1-year intervals. RESULTS: Of the 364 patients who completed the 52-week double-blind treatment period, 345 entered the 24-week extension, and 296 continued treatment with belimumab in the long-term continuation study. Safety data through 4 years of belimumab exposure (1,165 cumulative patient-years) are reported. Incidence rates of AEs, severe/serious AEs, infusion reactions, infections, malignancies, grades 3/4 laboratory abnormalities, and discontinuations due to AEs were stable or declined during 4-year belimumab exposure. The most common AEs included arthralgia, upper respiratory tract infection, headache, fatigue, and nausea. Serious infusion reactions were rare: only 1 occurred during the 4-year followup period. Rates of serious infection decreased from 5.9/100 patient-years to 3.4/100 patient-years, and no specific type of infection predominated. CONCLUSION: Belimumab added to standard therapy was generally well-tolerated over the 4-year treatment period in patients with SLE, which suggests that belimumab can be administered long term with an acceptable safety profile. PMID- 22674458 TI - Clinical severity of Huntington's disease does not always correlate with neuropathologic stage. AB - Huntington's disease (HD) is an inherited neurodegenerative disorder caused by a triplet-repeat, CAG expansion mutation. Although CAG repeat length is thought to correlate with pathologic burden and disease severity, considerable variability in clinical phenotype remains. This study examined whether neuropathologic burden at autopsy corresponded with severity of clinical phenotype in HD. The brains of 24 patients with a clinical and genetic diagnosis of HD were analyzed at autopsy. Subjects were stratified on the basis of Vonsattel staging as mild/moderate (stage 1-2; n = 7) or severe (stage 3-4; n = 17). Clinical severity was assessed on the basis of the Mini-Mental State Examination (MMSE; 0-30) and two Unified Huntington's Disease Rating Scale (UHDRS) functional components: the Independence Scale (10-100) and the Total Functional Capacity (0-13). Mild/moderate subjects were significantly older, had lower CAG repeat lengths, and greater fixed brain weights than those classified as severe. Patients who were pathologically classified as severe at autopsy were, on average, younger at age of onset and death and less well educated. Despite obvious clinical and pathological differences between mild-moderate and severe HD subjects at autopsy, mean MMSE scores of the two groups before death were surprisingly similar. Correlations between Vonsattel stage and functional assessment scores before death were low and not statistically significant. Our results suggest that the extent of striatal changes in HD may not always correlate with clinical disease severity as measured by UHDRS functional scales. PMID- 22674459 TI - Identification of physicochemical properties of Scylla paramamosain allergen, arginin kinase. AB - BACKGROUND: Arginine kinase (AK) is expressed in a wide variety of species, including human food sources (seafood) and pests (cockroaches and moths), and has been reported as a novel allergen. However, there has been little research on the allergenicity of AK in crustaceans. In this study the physicochemical properties of AK from mud crab (Scylla paramamosain) were investigated. RESULTS: Analysis by sodium dodecyl sulfate polyacrylamide gel electrophoresis, immunoblotting and inhibition enzyme-linked immunosorbent assay revealed that purified AK was unstable in thermal processing and in acid buffer. Under simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) conditions, purified AK was much more readily degraded by pepsin than by trypsin or chymotrypsin. The unpurified AK in crab myogen degraded more markedly than purified AK. In addition, in two-phase gastrointestinal digestion, AK was rapidly degraded by pepsin but resistant to trypsin and chymotrypsin digestion, while tropomyosin derived from mud crab was resistant to pepsin digestion but digested readily by trypsin or chymotrypsin. Further study of serum samples obtained from crab-allergic human patients indicated that the allergenicity of AK was markedly reduced by digestion with SGF but not SIF. CONCLUSION: AK is an important food allergen despite its unstable physicochemical properties of digestibility. PMID- 22674460 TI - LUTS patient reported outcomes tool: linguistic validation in 10 European languages. AB - AIM: To linguistically validate the translation of the Lower Urinary Tract Symptoms (LUTS) Tool from English to 10 European languages and assess whether the translations adequately reflected the concepts in the original version and if urological terms and the individual items were readily understood. METHODS: Residents of the target countries who spoke the native language and had LUTS were asked to evaluate a harmonized translation of the LUTS Tool, which was developed in 10 languages: Danish (Denmark), Dutch (Belgium, Netherlands), Finnish (Finland), French (Belgium, France, Luxembourg, and Switzerland), German (Germany, Switzerland), Greek (Greece), Icelandic (Iceland), Italian (Italy), Norwegian (Norway), and Spanish (Spain). After reviewing the language-appropriate version, participants were asked to explain why any words were difficult to understand and to paraphrase each sentence during a standardized cognitive debriefing interview. Linguistic validation teams (original translators, back translator, project manager, interviewer, and survey research expert) conducted a qualitative analysis of the cognitive debriefing findings. RESULTS: The terminology and concepts in the English-language version of the LUTS Tool were adequately captured in all language translations. The overall item comprehension rate, across languages, was 98.5%. Terms related to storage, voiding, and post micturition LUTS were comprehensible. Minor difficulties with comprehension were identified in 9 of 10 translations, and those changes were made to improve clarity. CONCLUSIONS: Individuals with LUTS from 10 countries understood the individual items captured in translated versions of the LUTS Tool. The overall comprehension rate was high. Most changes were made to improve conceptual clarity based on country-specific linguistic and cultural nuances. PMID- 22674461 TI - microRNAs as novel regulators of stem cell pluripotency and somatic cell reprogramming. AB - Emerging evidence suggests that microRNA (miRNA)-mediated post-transcriptional gene regulation plays an essential role in modulating embryonic stem (ES) cell pluripotency maintenance, differentiation, and reprogramming of somatic cells to an ES cell-like state. Investigations from ES cell-enriched miRNAs, such as mouse miR-290 cluster and human miR-302 cluster, and ES cell-depleted miRNAs such as let-7 family miRNAs, revealed a common theme that miRNAs target diverse cellular processes including cell cycle regulators, signaling pathway effectors, transcription factors, and epigenetic modifiers and shape their protein output. The combinatorial effects downstream of miRNA action allow miRNAs to modulate cell-fate decisions effectively. Furthermore, the transcription and biogenesis of miRNAs are also tightly regulated. Thus, elucidating the interplay between miRNAs and other modes of gene regulation will shed new light on the biology of pluripotent stem cells and somatic cell reprogramming. PMID- 22674462 TI - A prospective comparison of moderating relationships among stressors, hopelessness, and internalizing symptoms in low-income urban youth with asthma. AB - There are many risk factors associated with the development of internalizing symptoms in low-income urban youth, and youth with asthma appear to be at greater risk for experiencing stressors in multiple domains. The purpose of the current study was to examine stressors, hopelessness, and the interaction between them, as predictors of trajectories of anxious/depressed and withdrawn symptoms over a 4-year period of adolescence. Participating in the study were 53 youth from Chicago public schools, the majority of whom identified themselves as African American or Latino. Multi-level modeling was used to examine major life events, daily hassles, exposure to violence, poverty, and hopelessness as predictors of both types of symptoms. Major life events and exposure to violence predicted anxious/depressed symptoms but not withdrawn symptoms. Hopelessness predicted both types of symptoms and further interacted with major life events to predict both anxious/depressed and withdrawn symptoms. Hopelessness also moderated the effects of daily hassles on anxious/depressed symptoms and poverty on withdrawn symptoms. Results of this study provide insight into the psychosocial risk factors associated with the experience of asthma in urban adolescents. PMID- 22674463 TI - The prevalence of HIV, HBV, HCV, and HIV-related risk-taking behaviors among Palestinian injecting drug users in the East Jerusalem Governorate. AB - The objective of the study was to determine HIV, HBV, HCV seroprevalence and to assess HIV risks among Palestinian injecting drug users (IDUs) in the East Jerusalem Governorate. Following formative research, a bio-behavioral survey using respondent-driven sampling was carried out in 2010 among 199 IDUs aged 19 56 years(M=41.33, SD=8.09). Venous blood was drawn for biological testing. Data on drug abuse and sexual behaviors were collected by face-to-face interviewing. No HIV+cases were found. Five participants were infected with Hepatitis B and 84 participants(estimated population proportion of 40.3 %) tested positive for Hepatitis C. A great majority of the surveyed IDUs (90.4 %) reported using sterile injecting equipment the last time they injected. In a multivariate assessment, age (OR=2.52, pG.05), education(OR=6.67, pG.01), personal network size (OR=.18, pG.001), and the frequency of drug injecting in the past month (OR=.20, pG.001) were associated with using sterile injecting equipment in the past week. Condom use at most recent sexual intercourse was reported by about a third (34.2 %) of IDUs. The study documented substantial exposure to HIV risks among Palestinian IDUs whose vulnerability is inseparable from sociopolitic and socioeconomic characteristics of their social environment [corrected]. PMID- 22674464 TI - Experiences of racial discrimination and relation to sexual risk for HIV among a sample of urban black and African American men. AB - This study aimed to examine racial discrimination and relation to sexual risk for HIV among a sample of urban black and African American men. Participants of this cross-sectional study were black and African American men (N = 703) between the ages of 18 and 65 years, recruited from four urban clinical sites in the northeast. Multivariate logistic regression models were used to analyze the relation of reported racial discrimination to the following: (1) sex trade involvement, (2) recent unprotected sex, and (3) reporting a number of sex partners in the past 12 months greater than the sample average. The majority of the sample (96%) reported racial discrimination. In adjusted analyses, men reporting high levels of discrimination were significantly more likely to report recent sex trade involvement (buying and/or selling) (adjusted odds ratio (AOR) range = 1.7-2.3), having recent unprotected vaginal sex with a female partner (AOR = 1.4, 95% confidence interval (CI), 1.1-2.0), and reporting more than four sex partners in the past year (AOR = 1.4, 95% CI, 1.1-1.9). Findings highlight the link between experiences of racial discrimination and men's sexual risk for HIV. PMID- 22674465 TI - Diastereodivergent synthesis of 3-spirocyclopropyl-2-oxindoles through direct enantioselective cyclopropanation of oxindoles. PMID- 22674466 TI - Enhancing Bayesian risk prediction for epidemics using contact tracing. AB - Contact-tracing data (CTD) collected from disease outbreaks has received relatively little attention in the epidemic modeling literature because it is thought to be unreliable: infection sources might be wrongly attributed, or data might be missing due to resource constraints in the questionnaire exercise. Nevertheless, these data might provide a rich source of information on the disease transmission rate. This paper presents a novel methodology for combining CTD with rate-based contact network data to improve posterior precision, and therefore predictive accuracy. We present an advancement in Bayesian inference for epidemics that assimilates these data and is robust to partial contact tracing. Using a simulation study based on the British poultry industry, we show how the presence of CTD improves posterior predictive accuracy and can directly inform a more effective control strategy. PMID- 22674467 TI - Modelling the impacts of new diagnostic tools for tuberculosis in developing countries to enhance policy decisions. AB - The introduction and scale-up of new tools for the diagnosis of Tuberculosis (TB) in developing countries has the potential to make a huge difference to the lives of millions of people living in poverty. To achieve this, policy makers need the information to make the right decisions about which new tools to implement and where in the diagnostic algorithm to apply them most effectively. These decisions are difficult as the new tools are often expensive to implement and use, and the health system and patient impacts uncertain, particularly in developing countries where there is a high burden of TB. The authors demonstrate that a discrete event simulation model could play a significant part in improving and informing these decisions. The feasibility of linking the discrete event simulation to a dynamic epidemiology model is also explored in order to take account of longer term impacts on the incidence of TB. Results from two diagnostic districts in Tanzania are used to illustrate how the approach could be used to improve decisions. PMID- 22674468 TI - Retrospective comparison of filgrastim plus plerixafor to other regimens for remobilization after primary mobilization failure: clinical and economic outcomes. AB - We performed a retrospective analysis to evaluate clinical and economic outcomes in patients receiving remobilization therapy after primary mobilization failure. Our primary endpoint was to compare filgrastim plus plerixafor to other regimens in their ability to collect a target cell dose of at least 2 million CD34+ cells/kg (cumulative). Of 96 consecutive patients who failed their primary mobilization therapy and in whom a second mobilization was attempted, remobilization consisted of filgrastim plus plerixafor (n = 38), filgrastim with or without sargramostim (n = 43), or chemotherapy plus filgrastim (n = 15), 84% of filgrastim/plerixafor patients were able to collect at least 2 million CD34+ cells/kg from both mobilizations, compared to 60% of patients mobilized with chemotherapy/filgrastim and 79% of the filgrastim +/- sargramostim patients (P = 0.17). However, when combined with cells collected from the first mobilization, 53% of filgrastim/plerixafor patients reached the target of 2 million CD34+ cells in one apheresis, compared to 20% of those receiving chemotherapy/filgrastim and 28% of those receiving filgrastim +/- sargramostim (P = 0.02). Resource utilization, mobilization drug costs, clinical care costs, and total costs were significantly different. We conclude that while filgrastim/plerixafor is the most efficient remobilization strategy, those clinical benefits may not translate into lower cost, especially when multiple days of plerixafor administration are required. PMID- 22674469 TI - An ex vivo perfusion system emulating in vivo conditions in noncirrhotic and cirrhotic human liver. AB - Various models are used for investigating human liver diseases and testing new drugs. However, data generated in such models have only limited relevance for in vivo conditions in humans. We present here an ex vivo perfusion system using human liver samples that enables the characterization of parameters in a functionally intact tissue context. Resected samples of noncirrhotic liver (NC; n = 10) and cirrhotic liver (CL; n = 12) were perfused for 6-h periods. General and liver-specific parameters (glucose, lactate, oxygen, albumin, urea, and bile acids), liver enzymes (aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, glutamate dehydrogenase, and gamma-glutamyl transferase), overall (M65) and apoptotic (M30) cell-death markers, and indicators of phase I/phase-II biotransformations were analyzed. The measurement readings closely resembled (patho)physiological characteristics in patients with NC and CL. Mean courses of glucose levels reflected the CLs' reduced glycogen storage capability. Furthermore, CL samples exhibited significantly stronger increases in lactate, bile acids, and the M30/M65 ratio than NC specimens. Likewise, NC samples exhibited more rapid phase-I transformations of phenacetin, midazolam, and diclofenac and phase-I to phase-II turnover rates of the respective intermediates than CL tissue. Collectively, these findings reveal the better hepatic functionality in NC. Perfusion of human liver tissue with this system emulates in vivo conditions and clearly discriminates between noncirrhotic and cirrhotic tissue. This highly reliable device for investigating basic hepatic functionality and testing safety/toxicity, pharmacokinetics/pharmacodynamics and efficacies of novel therapeutic modalities promises to generate superior data compared with those obtained via existing economic perfusion systems. PMID- 22674470 TI - Phenanthrene metabolism in smokers: use of a two-step diagnostic plot approach to identify subjects with extensive metabolic activation. AB - Polycyclic aromatic hydrocarbons (PAHs) in cigarette smoke are among the most likely causes of lung cancer. PAHs require metabolic activation to initiate the carcinogenic process. Phenanthrene (Phe), a noncarcinogenic PAH, was used as a surrogate of benzo[alpha]pyrene and related PAHs to study the metabolic activation of PAHs in smokers. A dose of 10 MUg of deuterated Phe ([D10]Phe) was administered to 25 healthy smokers in a crossover design, either as an oral solution or by smoking cigarettes containing [D10]Phe. Phe was deuterated to avoid interference from environmental Phe. Intensive blood and urine sampling was performed to quantitate the formation of deuterated r-1,t-2,3,c-4-tetrahydroxy 1,2,3,4-tetrahydrophenanthrene ([D10]PheT), a biomarker of the diol epoxide metabolic activation pathway. In both the oral and smoking arms approximately 6% of the dose was metabolically converted to diol epoxides, with a large intersubject variability in the formation of [D10]PheT observed. Two diagnostic plots were developed to identify subjects with large systemic exposure and significant lung contribution to metabolic activation. The combination of the two plots led to the identification of subjects with substantial local exposure. These subjects produced, in one single pass of [D10]Phe through the lung, a [D10]PheT exposure equivalent to the systemic exposure of a typical subject and may be an indicator of lung cancer susceptibility. Polymorphisms in PAH metabolizing genes of the 25 subjects were also investigated. The integration of phenotyping and genotyping results indicated that GSTM1-null subjects produced approximately 2-fold more [D10]PheT than did GSTM1-positive subjects. PMID- 22674471 TI - Deciduous dental pulp stem cells are involved in osteoclastogenesis during physiologic root resorption. AB - Multipotent mesenchymal stem cells are derived from the dental pulps of permanent teeth and exfoliated deciduous teeth, and are known to induce bone and dentin generation. However, the role of deciduous dental pulp stem cells (DDPSCs) in physiologic root resorption remains unclear. In this study, dental pulp stem cells (DPSCs) in permanent teeth (P) were retrieved and compared to DDPSCs from deciduous incisors at different root resorption stages: stable (S), middle (M), and final (F). Decalcified teeth sections showed that osteoclasts and resorption lacunae were most prevalent in the M resorption stage. DDPSC proliferation rate was also highest in the M stage. DDPSCs in the F stage produced more calcified nodules than those in the S or M stages. Alkaline phosphatase (ALP) expression was highest in the F stage, indicating that DDPSCs promote mineralization. In addition, the ratio of receptor activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG) expression was significantly higher in the M stage, indicating that DDPSCs promote resorption. Dickkopf 1 (Dkk1) expression was remarkably higher in the F and P groups, suggesting that the Wnt pathway is inhibited during the resorption process. Interestingly, despite the fact that Wnt3a down-regulated OPG in osteogenic induction medium and up-regulated RANKL in medium with 1,25-dihydroxy vitamin D3 (VD(3) ), the RANKL/OPG ratio was reduced only with VD(3) . Collectively, our data indicate that DDPSCs influence osteoclastogenesis during the physiologic root resorption process, and that the canonical Wnt pathway can change the RANKL/OPG expression ratio in DDPSCs. PMID- 22674472 TI - Confined 3D microenvironment regulates early differentiation in human pluripotent stem cells. AB - The therapeutic potential of human pluripotent stem (hPS) cells is threatened, among various problems, by the difficulty to homogenously direct cell differentiation into specific lineages. The transition from hPSC into committed differentiated cells is accompanied by secretome activity, remodeling of extracellular matrix and self-organization into germ layers. In this work, we aimed to investigate how different three-dimensional microenvironments regulate the early differentiation of the three germ layers in human embryonic stem (hES) cells derived embryoid bodies. In particular, a permeable, biocompatible, hydrogel microwell array was specifically designed for recreating a confined niche in which EB secreted molecules accumulate in accordance with hydrogel diffusional cut-off. Fluorescence recovery after photobleaching technique was performed to accurately evaluate hydrogel permeability, mesh size and diffusional cutoff for soluble molecules. Three different culture conditions of EB culture were analyzed: suspension, confinement in microwells of width/depth ratio 1:1 and 1:2. Results show that EBs cultured in microwells are viable and have comparable average size after 8 days culture. Whole genome microarrays show that significative differential gene expression was observed between suspension and confined EBs culture. In particular, EBs culture in microwells promotes the expression of genes involved in pattern specification processes, brain development, ectoderm and endoderm differentiation. On the contrary, suspension EBs express instead genes involved in mesoderm specification and heart development. These results suggest that local accumulation of EBs secreted molecules drives differentiation patterns, as confirmed by immunofluorescence of germ layer markers, in hydrogel confined EB culture from both hES cells and human induced pluripotent stem (hiPS) cells. Our findings highlight an additional potential role of biomaterial in controlling hPSC differentiation through secreted factor niche specification. PMID- 22674473 TI - Improvement of hyperphagia by activation of cerebral I(1)-imidazoline receptors in streptozotocin-induced diabetic mice. AB - Imidazoline I1-receptors (I1R) are known to regulate blood pressure and rilmenidine, an agonist, is widely used as antihypertensive agent in clinic. However, the role of I1R in feeding behavior is still unclear. In the present study, we used the agonist of I1R to investigate the effect on hyperphagia in streptozotocin (STZ)-induced diabetic mice. Rilmenidine decreased the food intake of STZ-diabetic mice in a dose-dependent manner. The reduction of food intake was abolished by pretreatment with efaroxan at the dose sufficient to block I1R. Intracerebroventricular (icv) administration of rilmenidine into STZ-diabetic mice also significantly reduced hyperphagia, which was reversed by icv administration of efaroxan. In addition, similar results were observed in STZ diabetic mice, which received chronic treatment with rilmenidine 3 times daily (t.i.d.) for 7 days. Moreover, the hypothalamic neuropeptide Y (NPY) level was reduced by rilmenidine that was also reversed by pretreatment with efaroxan. In conclusion, the obtained results suggest that rilmenidine can decrease food intake in STZ-diabetic mice through an activation of I1R to lower hypothalamic NPY level. PMID- 22674474 TI - Allopregnanolone alters the luteinizing hormone, prolactin, and progesterone serum levels interfering with the regression and apoptosis in rat corpus luteum. AB - Steroids synthesized in the central nervous system are termed "neurosteroids". They are synthesized and metabolized in several brain areas. The objective of this work was to determine if 1 intracerebroventricular allopregnanolone injection in rats can interfere in luteal regression in a close relationship with modifications in LH, progesterone, and prolactin serum concentrations. Allopregnanolone was injected during proestrus morning and the animals were sacrificed on oestrous morning. Ovulation test and histological analysis were performed in the oestrus morning with light and electron microscopy. Serum prolactin, LH, and progesterone levels were measured by radioimmunoassay. The allopregnanolone injection significantly decreased luteinizing hormone serum level and the number of oocytes on oestrus. Progesterone and prolactin serum levels were increased after this injection. The inhibition of apoptotic figures due to allopregnanolone administration was detected in the already formed corpora lutea belonging to the previous ovary cycle and it was significantly lower than in vehicle group (control). When the GABA(A) antagonist (bicuculline) was administered alone or previously to allopregnanolone, no effect on the ovulation rate was observed. No changes in the apoptotic cell numbers were observed with respect to those of vehicle group. These results show that the effect of centrally injected allopreganolone over reproductive function could be due to a centrally originated LH mediated effect over ovarian function that affects luteal regression, through the inhibition of apoptosis and stimulation of progesterone and prolactin release. PMID- 22674475 TI - Diagnosis of growth hormone deficiency is affected by calibrators used in GH immunoassays. AB - Growth hormone (GH) values vary among immunoassays depending on different factors, such as the assay method used, specificity of antibodies, matrix difference between standards and samples, and interference with endogenous GH binding proteins (GHBPs). We evaluated whether the use of different calibrators for GH measurement may affect GH values and, consequently, the formulation of GH deficiency (GHD) diagnosis in children. Twenty-three short children (5 F, 18 M; age 11.4+/-3.1 years), with the clinical characteristics of GHD (height: -2.3+/ 0.5 SDS; height velocity -2.3+/-1.5 SDS; IGF-I -1.2+/-0.9 SDS), underwent GH stimulation tests to confirm the clinical diagnosis of GHD. Serum GH values were measured with Immulite 2000, using 2 different calibrators, IS 98/574, a recombinant 22 kDa molecule of more than 95% purity, and IS 80/505, of pituitary origin and resembling a variety of GH isoforms. We found blunted GH secretion in 20 subjects with the Immulite assay using the IS 98/574 GH as a calibrator, confirming the diagnosis of GHD. Subsequently, using IS 80/505 GH as a calibrator, in the same samples only 14 children showed reduced GH levels. The total cost for the first year of GH therapy of patients diagnosed with IS 98/574 as a calibrator was higher than that for patients diagnosed with IS 80/505 as a calibrator. These data confirm that GH values may depend on different calibrators used in the GH assay, affecting the formulation of GHD diagnosis and the consequent decision to start GH treatment. PMID- 22674476 TI - Effect of dietary macronutrient composition on AMPK and SIRT1 expression and activity in human skeletal muscle. AB - Adenosine monophosphate-activated protein kinase (AMPK), silent mating type information regulation 2 homologue 1 (SIRT 1), and peroxisome proliferator activated receptor gamma co-activator alpha (PGC1alpha) constitute an energy sensing cellular network that controls mitochondrial biogenesis. Caloric restriction activates both AMPK and SIRT-1 to increase ATP production from fat oxidation. We characterized AMPK and SIRT 1 expression and activity in human skeletal muscle in response to dietary fat or carbohydrate intake on the background of either overfeeding or caloric restriction. AMPK phosphorylation and acetylation of PGC1alpha (as a measure of SIRT activity) were determined. Euglycemic-hyperinsulinemic clamp and muscle biopsies were performed in human subjects participating in 2 separate studies. In study 1, 21 lean healthy individuals were overfed for 5 days, while in study 2, 18 obese otherwise healthy individuals consumed a calorie-restricted diet for 5 days. Under both conditions overfeeding and caloric restriction - high fat/low carbohydrate (HF/LC) diet significantly increased phosphorylation of AMPK and deacetylation of PGC1alpha in skeletal muscle without affecting total amounts of AMPK, PGC1alpha, or SIRT 1. In contrast, low fat/high carbohydrate (LF/HC) hypocaloric diet reduced phosphorylation of AMPK and deacetylation of PGC1alpha. Our data indicate that a relative deficiency in carbohydrate intake or, albeit less likely, a relative excess of fat intake even in the absence of caloric deprivation is sufficient to activate the AMPK-SIRT 1-PGC1alpha energy-sensing cellular network in human skeletal muscle. PMID- 22674477 TI - GNAS epigenetic defects and pseudohypoparathyroidism: time for a new classification? AB - Pseudohypoparathyroidism-Ia and -Ib (PHP-Ia and -Ib) are caused by mutations in GNAS exons 1-13 and methylation defects in the imprinted GNAS cluster, respectively. PHP-Ia patients show Albright hereditary osteodystrophy (AHO), together with resistance to the action of different hormones that activate the Gs coupled pathway. In PHP-Ib patients AHO is classically absent and hormone resistance is limited to PTH and TSH. This disorder is caused by GNAS methylation alterations with loss of imprinting at the exon A/B differentially methylated region (DMR) being the most consistent and recurrent defect. The familial form of the disease (AD-PHP-Ib) is typically associated with an isolated loss of imprinting at the exon A/B DMR due to microdeletions disrupting the upstream STX16 gene. In addition, deletions removing the entire NESP55 DMR, located within GNAS, associated with loss of all the maternal GNAS imprints have been identified in some AD-PHP-Ib kindreds. Conversely, most sporadic PHP-Ib cases have GNAS imprinting abnormalities that involve multiple DMRs, but the genetic lesion underlying these defects is unknown. Recently, methylation defects have been detected in a subset of patients with PHP-Ia and variable degrees of AHO, indicating a molecular overlap between the 2 forms. Imprinting defects do not seem to be associated with the severity of AHO neither with specific AHO signs. In conclusion, the latest findings on the molecular basis underlying these defects suggest the existence of a clinical and genetic/epigenetic overlap between PHP-Ia and PHP-Ib, and highlight the necessity of a new clinical classification of these disorders based on molecular findings. PMID- 22674479 TI - Accessory foramen in the human mandible: anatomical and clinical considerations. PMID- 22674478 TI - Pathologic characteristics of second breast cancers after breast conservation for ductal carcinoma in situ. AB - BACKGROUND: The number of women diagnosed with ductal carcinoma in situ (DCIS) is increasing. Although many eventually develop a second breast cancer (SBC), little is known about the characteristics of SBCs. The authors described the characteristics of SBC and examined associations between the pathologic features of SBC and index DCIS cases. METHODS: Women were identified in the National Comprehensive Cancer Network Outcomes Database who were diagnosed with DCIS from 1997 to 2008 and underwent lumpectomy and who subsequently developed SBC (including DCIS or invasive disease that occurred in the ipsilateral or contralateral breast). The Fisher exact test and the Spearman test were used to examine associations between the pathologic characteristics of SBC and index DCIS cases. RESULTS: Among 2636 women who underwent lumpectomy for DCIS, 150 (5.7%) experienced an SBC after a median of 55.5 months of follow-up. Of these 150 women, 105 (70%) received adjuvant radiotherapy, and 50 (33.3%) received tamoxifen for their index DCIS. SBCs were ipsilateral in 54.7% of women and invasive in 50.7% of women. Among the index DCIS cases, 60.6% were estrogen receptor (ER)-positive, and 54% were high grade, whereas 77.5% of SBCs were ER positive, and 48.2% were high grade. Tumor grade (P = .003) and ER status (P = .02) were associated significantly between index DCIS and SBC, whereas tumor size was not (P = .87). CONCLUSIONS: After breast conservation for DCIS, SBC in either breast exhibited pathologic characteristics similar to the index DCIS, suggesting that women with DCIS may be at risk for developing subsequent breast cancers of a similar phenotype. PMID- 22674480 TI - Highly efficient and exact method for parallelization of grid-based algorithms and its implementation in DelPhi. AB - The Gauss-Seidel (GS) method is a standard iterative numerical method widely used to solve a system of equations and, in general, is more efficient comparing to other iterative methods, such as the Jacobi method. However, standard implementation of the GS method restricts its utilization in parallel computing due to its requirement of using updated neighboring values (i.e., in current iteration) as soon as they are available. Here, we report an efficient and exact (not requiring assumptions) method to parallelize iterations and to reduce the computational time as a linear/nearly linear function of the number of processes or computing units. In contrast to other existing solutions, our method does not require any assumptions and is equally applicable for solving linear and nonlinear equations. This approach is implemented in the DelPhi program, which is a finite difference Poisson-Boltzmann equation solver to model electrostatics in molecular biology. This development makes the iterative procedure on obtaining the electrostatic potential distribution in the parallelized DelPhi several folds faster than that in the serial code. Further, we demonstrate the advantages of the new parallelized DelPhi by computing the electrostatic potential and the corresponding energies of large supramolecular structures. PMID- 22674482 TI - [Bone infections]. PMID- 22674483 TI - [Bone infections]. AB - Even in recent traumatology and orthopedic surgery infectious diseases of the bone (i.e. osteomyelitis) and it's surrounding tissues remain serious complications. The therapy is demanding and oftenly does not lead to a complete restitutio ad integrum. In order to create the optimal treatment one has to have a profound knowledge about the "state of the art" therapy of bone infections and the basic phases: Reassurance of the local infection (bone and surrounding tissues) and reconstruction of the bone and surrounding tissues. The local infection treatment is based on the consequent surgical eradication of infected tissue. In addition (as a supportive therapy) antibiotics have to be applied according to the local and systemic response of the patient to the infection. Also further supportive methods like hyperbaric oxygenation may be taken into consideration. The following paper provides an overview of diagnostic features and the different surgical procedures as well as the current literature in order to reach the above mentioned goals. PMID- 22674484 TI - [Joint infections. Known facts and new trends]. AB - Acute septic arthritis is a surgical emergency because rapid septic destruction of articular cartilage can lead to impairment or even loss of joint function. Diagnosis consists of patient history, clinical examination, laboratory results, (sonography- guided) joint aspiration and radiography. Emergency therapy is based on arthroscopic or open joint debridement and lavage combined with systemic antibiotic therapy. No data are available for the recommendation of local antibiotics but antiseptic solutions are not recommended because of cartilage damage. New trends in diagnostics are positron emission tomography/computed tomography (PET/CT), urine sticks for analysis of joint fluid and molecular pathology. Chronic joint empyema is more diagnostically demanding and is difficult to treat. In cases of necrotic and infected articular cartilage, joint resection has to be performed for quiescence of infection. Options following successful treatment of empyema are arthroplasty, arthrodesis or permanent resection. PMID- 22674485 TI - [Diagnosis and treatment of periprosthetic infections]. AB - The differentiation of periprosthetic infections into early onset and late onset infections is the determining factor fores the therapeutic strategy. The diagnosis of chronic unapparent infections is sometimes difficult. The therapeutic success, especially in early onset infections, is essentially influenced by a well-timed diagnosis and an immediate therapy. Surgical wound debridement with preservation of the prosthesis, one-stage replacement and two stage replacement all with concomitant appropriate systemically administered double combined antibiotics are therapeutic options depending on factors, such as the duration of the infection. Prosthesis replacement is currently the only option to treat biofilm colonization of endoprosthetic surfaces. The bacterial adhesion on polyethylene can be extremely resistant. Due to the therapeutic consequences, periprosthetic infections remain one of the worst complications in endoprosthetic joint replacement. PMID- 22674486 TI - [Shoulder stiffness]. AB - Primary shoulder stiffness is idiopathic. Due to coincidence with other diseases, a systemic genesis with hormonal influence is discussed. The result of chronic inflammation with fibroblastic proliferation is a fibrotic capsule, atrophy of ligaments, and muscular dysbalance. The main symptom is painful restricted passive and active shoulder motion. There is a high rate of unsatisfactory courses. Therapy depends on the phase and duration of shoulder stiffness. Primary treatment of choice is oral steroid therapy, followed by physical and physiotherapy. Steroids can be applied intraarticular, as an alternative. If conservative treatment fails after a period of 6 months, arthroscopic arthrolysis is indicated. Secondary shoulder stiffness often results from traumatization or operation of the shoulder. Primary treatment is also conservative, but operative intervention should be performed early after unsuccessful therapy. Intensive, passive mobilization is necessary after arthrolysis. PMID- 22674487 TI - [Late infections after open reduction and internal fixation of the upper ankle joint]. AB - A 63-year-old patient suffering from diabetes mellitus and arterial occlusive disease sustained a displaced fracture of the upper ankle joint. The fracture was treated by open reduction and internal fixation (ORIF) but 6 months later a delayed infection developed. Partial implant removal and a single lavage were performed. With persistent signs of infection full implant removal and subsequently debridement and lavage were carried out 3.5 months later followed by arthrodesis of the upper ankle joint. The arbitration board decided that the treatment applied after diagnosing the delayed infection was not sufficient which led to a delay in appropriate treatment. However, whether the arthrodesis of the upper ankle joint could have been prevented could not be proven. PMID- 22674488 TI - Th17 cells are restrained by Treg cells via the inhibition of interleukin-6 in patients with rheumatoid arthritis responding to anti-tumor necrosis factor antibody therapy. AB - OBJECTIVE: The importance of interleukin-17 (IL-17) is underscored both by its resistance to control by Treg cells and the propensity of Treg cells to produce this highly inflammatory cytokine. This study sought to address whether Th17 cells are inhibited by Treg cells in rheumatoid arthritis (RA) patients responding to anti-tumor necrosis factor (anti-TNF) therapy, and if so defining the underlying mechanisms of suppression. METHODS: Inhibition of Th17 cell responses was determined by Treg cell suppression assays. The Treg cell phenotype was analyzed using flow cytometry and enzyme-linked immunosorbent assay. Mechanisms of suppression were tested by cytokine addition or antibody blockade. RESULTS: Th17 responses were inhibited by Treg cells from RA patients responding to the anti-TNF antibody adalimumab (Treg(ada) ), but not by Treg cells from healthy individuals or patients with active RA. Furthermore, Treg(ada) cells secreted less IL-17, even when exposed to proinflammatory monocytes from patients with active RA. Treg(ada) cells suppressed Th17 cells through the inhibition of monocyte-derived IL-6, but this effect was independent of IL-10 and transforming growth factor beta, which mediated the suppression of Th1 responses. Adalimumab therapy led to a reduction in retinoic acid receptor-related orphan nuclear receptor C-positive Th17 cells and an increase in FoxP3+ Treg cells lacking expression of the transcription factor Helios. However, this acquisition of IL-17 suppressor function was not observed in RA patients responding to treatment with etanercept, a modified TNF receptor-Fc fusion protein. Indeed, there was no alteration in Treg cell number, function, or phenotype in etanercept-treated patients, and Th17 responses remained unchecked. CONCLUSION: Th1 and Th17 responses are controlled through distinct mechanisms by Treg cells from patients responding to anti-TNF antibody therapy. Adalimumab therapy, but not etanercept therapy, induces a potent and stable Treg cell population with the potential to restrain the progression of IL-17-associated inflammation in RA via regulation of monocyte-derived IL-6. PMID- 22674489 TI - New vistas for treatment of obesity and diabetes? Endocannabinoid signalling and metabolism in the modulation of energy balance. AB - Growing evidence suggests that pathological overactivation of the endocannabinoid system (ECS) is associated with dyslipidemia, obesity and diabetes. Indeed, this signalling system acting through cannabinoid receptors has been shown to function both centrally and peripherally to regulate feeding behaviour as well as energy expenditure and metabolism. Consequently, modulation of these receptors can promote significant alterations in body weight and associated metabolic profile. Importantly, blocking cannabinoid receptor type 1 function has been found to prevent obesity and metabolic dysfunction in various murine models and in humans. Here we provide a detailed account of the known physiological role of the ECS in energy balance, and explore how recent studies have delivered novel insights into the potential targeting of this system as a therapeutic means for treating obesity and related metabolic disorders. PMID- 22674490 TI - Diversity of the juxtamembrane and TKD1 mutations (exons 13-15) in the FLT3 gene with regards to mutant load, sequence, length, localization, and correlation with biological data. AB - In acute myeloid leukemia (AML) mutations in the juxtamembrane and tyrosine kinase 1 domain (exons 13-15) of the FLT3 gene (FLT3-ITD/LM) are heterogeneous with respect to mutation load, size, and localization. We characterized length and structure of these mutations by fragment analysis and sequencing in 689 AML which were identified among 3,365 (20.5%) newly diagnosed AML (1,803 males, 1,562 females; 15.8-91.8 years). Mutations were heterogeneous in length (median: 63, range: 3-1,236 nucleotides; nt). Most frequent were sizes of 21 (8.4%) or 24 nt (6.0%). Ninety-one different insertion sites were observed (between nt 1,788 and 1,934, according to accession "FLT3 [Ensembl/Havana merge: ENSG00000122025]" with nt 1,856 (n = 41) and 1,863 (n = 35) being most frequent. In addition, 89 different insertion end points were observed between nt 1,790 and 1,994. FLT3 mutation/wild-type ratio was available in 615 patients (median, 0.80; range 0.03 181.73). 128 Patients (20.8%) had ratios <0.3, 334 (54.3%) had ratio >=0.3 <1, 118 (19.2%) >=1, and 35 (5.7%) showed complete loss of the FLT3-wild-type allele. Overall (OS) and event-free (EFS) survival were better for FLT3-negative than FLT3mut normal karyotype patients (P = 0.078 and P = 0.004, respectively) and patients with low level FLT3-mutations had significantly longer OS and EFS compared with high level mutations (FLT3-mutation/wild-type ratio >=1) (P < 0.001 and P = 0.002, respectively). The length of the mutation had no prognostic impact. Mutations localized more 5' were associated with better outcome than more 3'mutations, but no strict association to certain functional domains was detected. In conclusion, FLT3-mutations are extremely heterogenous with mutation load being the most relevant parameter. PMID- 22674491 TI - Anaplastic carcinoma of the thyroid gland: treatment and outcome over 13 years at one institution. AB - BACKGROUND: Anaplastic thyroid carcinoma (ATC) is a highly aggressive malignancy of the thyroid gland. Patients at our institution are treated with external radiotherapy up to 46 Gray (Gy) and low-dose doxorubicin prior to surgery. We retrospectively evaluated the outcome of ATC patients over a 13-year period. METHODS: Clinical, histopathological, and follow-up data for 59 patients diagnosed between 1997 and 2010 were collected and analyzed. RESULTS: Median age at diagnosis was 77 years. Female-male ratio was 2.5:1. Median survival from time of diagnosis was 3.3 months. Thirty-six patients completed the treatment protocol (including surgery), of whom one succumbed due to local tumor growth. In multivariate analysis, the only factor significantly associated with longer survival among operated patients was absence of metastases at diagnosis (P = 0.031). No impact on survival time was found for gender, extent of surgical resection, and absence of extrathyroidal invasion. CONCLUSIONS: Despite aggressive treatment, survival rates in ATC patients remain low. Locoregional control is feasible for most patients, underscoring the importance of an intense, multimodal treatment regimen. Further oncological intervention is of crucial importance to achieve a better prognosis for ATC patients. PMID- 22674492 TI - Expanding the scope of arylsulfonylacetylenes as alkynylating reagents and mechanistic insights in the formation of Csp2-Csp and Csp3-Csp bonds from organolithiums. AB - We describe the unexpected behavior of the arylsulfonylacetylenes, which suffer an "anti-Michael" addition of organolithiums producing their alkynylation under very mild conditions. The broad scope, excellent yields, and simplicity of the experimental procedure are the main features of this methodology. A rational explanation of all these results can be achieved by theoretical calculations, which suggest that the association of the organolithiums to the electrophile is a previous step of their intramolecular attack and is responsible for the unexpected "anti-Michael" reactions observed for substituted sulfonylacetylenes. PMID- 22674493 TI - Sustained therapeutic effects of percutaneous tibial nerve stimulation: 24-month results of the STEP study. AB - AIMS: To evaluate the safety, sustained effectiveness, and treatment interval for percutaneous tibial nerve stimulation (PTNS) for overactive bladder (OAB) therapy through 24 months. METHODS: A prospective study following treatment success after 12 weekly PTNS treatments, subjects were prescribed a 14-week tapering protocol, followed by ongoing therapy with a Personal Treatment Plan determined by the investigator and subject to sustain subject OAB symptom improvement. Questionnaires were completed every 3 months, voiding diaries every 6 months; adverse events were reported throughout. RESULTS: Of 50 subjects enrolled, 35 remained in the study at 24 months. During the 24 months following initial treatment success and a 14-week tapering protocol, mean treatments per month was 1.3. Voiding diary and OAB-q data demonstrate sustained improvement reported at 13 weeks through 24 months. Improvements in frequency, urge incontinence episodes, night-time voids and moderate-to-severe urgency episodes from voiding diaries at 6, 12, 18, and 24 months were statistically significant compared to baseline (prior to initial 12 weekly treatments). Compared to baseline, OAB-q symptom severity scores and health related quality of life scores were statistically significant for improvement at each tested time point. Five mild adverse events of unknown relation to treatment were reported. CONCLUSION: Sustained safety and efficacy of PTNS were demonstrated over 24 months with initial success after 12 weekly treatments, followed by a 14-week prescribed tapering protocol and a Personalized Treatment Plan. With an average of 1.3 treatments per month, PTNS therapy is a safe, durable, and valuable long-term OAB treatment option to sustain clinically significant OAB symptom control. PMID- 22674494 TI - Mechanism of the prokaryotic transmembrane disulfide reduction pathway and its in vitro reconstitution from purified components. AB - Making your (Dsb) connection: the redox pathway bringing reducing equivalents from bacterial cytoplasm, across the inner membrane, to the three reductive Dsb pathways in the otherwise oxidizing periplasm (see scheme; TR=thioredoxin reductase, Trx=thioredoxin) is reconstituted from purified components. Transfer of reducing equivalents across the membrane is demonstrated and underlying mechanistic details are revealed. PMID- 22674495 TI - Effects of 1-methylcyclopropene and post-controlled atmosphere air storage treatments on fresh-cut Ambrosia apple slices. AB - BACKGROUND: The effect of 1-methylcyclopropene (1-MCP) treatment and two different post-controlled atmosphere air storage (PCAAS) durations on the quality and chemistry of fresh-cut Ambrosia apple slices was studied. RESULTS: PCAAS for 1 or 2 weeks prior to slicing had an overall positive effect on the resultant quality of fresh-cut apple slices. The most significant responses to PCAAS were the suppression of both phenolic and o-quinone accumulation in slices, and this was related to the significantly lower browning potential values obtained for slices from PCAAS-treated apples. Polyphenol oxidase (PPO), peroxidase (POX) and ascorbate peroxidase (APOX) activities were not affected by 1-MCP or PCAAS treatments. PPO and POX activities were almost completely inhibited by a 50 g L-1 calcium ascorbate anti-browning dip of apple slices from all treatments. CONCLUSION: The most dramatic effect of the PCAAS treatments was to reduce the accumulation of soluble phenolics, which is likely the reason that o-quinone accumulation was also inhibited in treated fruits. The consequent reduction in browning potential may be the explanation as to why PCAAS treatment has been shown to reduce fresh apple slice browning in previous work. PMID- 22674496 TI - Post-treatment of dextromethorphan on methamphetamine-induced drug-seeking and behavioral sensitization in rats. AB - In our previous study, we first demonstrated a significant effect of dextromethorphan (DM) on morphine-seeking behavior in morphine-dependent rats, when DM was given during morphine withdrawal. Using the same conditioned place preference (CPP) paradigm modified for measuring drug-seeking-related behavior, we further investigated the possible effect of DM on methamphetamine (MA)-seeking in MA-dependent rats. Our data showed that DM could also effectively suppress the drug-seeking behavior for MA, when administered during MA withdrawal. This suggests that DM may possess a pharmacological property to prevent drug-seeking behavior for addictive drugs in general. To examine the action sites of DM in the brain, DM was microinjected into the VTA or the NAc, and tested for its effect on MA-seeking during withdrawal. Both intra-VTA and intra-NAc injections of DM were able to block the MA-seeking, suggesting that DM has a dual action sites. In our neurochemical results, intra-NAc injection of DM showed a clear reduction of DA turnover rate at the NAc and the mPFC in response to MA challenge during withdrawal, which matched with the behavioral results. However, intra-VTA injection of DM reduced the DA turnover rate at the mPFC but did not have effect on the DA turnover rate at the NAc. Although further investigations may be needed to verify the connection between our neurochemical and behavioral results, the present study highlights the therapeutic potential of DM in antidrug-seeking behavior of MA and that the mechanism could be related to its effect on the mesolimbic and mesocortical dopaminergic pathways. PMID- 22674497 TI - FDA's tobacco products research program likely to play role in cancer prevention: Large-scale study, grant funding among program's efforts. PMID- 22674499 TI - Scientists develop new tool for targeted cancer drug development. PMID- 22674501 TI - Effect of neonatal respiratory infection on adult BALB/c hippocampal glucocorticoid and mineralocorticoid receptors. AB - The current study investigated the effects of neonatal infection with Chlamydia muridarum bacteria on glucocorticoid (GR) and mineralocorticoid (MR) receptors in the adult mouse hippocampus. In male adults infected at birth, circulating corticosterone was significantly increased when compared to same sex controls; while neonatal infection resulted in female adults with significantly increased GR mRNA compared to same sex controls. When comparing males and females after neonatal infection, males had significantly less GR protein than females. Interestingly, after control treatment, males had significantly more GR mRNA, MR mRNA, and GR protein with significantly lower corticosterone than females. Neonatal respiratory infection significantly impacts adult hippocampal GR and MR, and circulating corticosterone in a sex-specific manner potentially altering stress responsivity. PMID- 22674502 TI - Comparative secretome analysis of human bone marrow-derived mesenchymal stem cells during osteogenesis. AB - Osteogenesis is a tightly regulated process that involves coordinated extracellular signals from autocrine and paracrine loops. Secretory proteins during osteogenesis can inhibit cell proliferation and activate cell differentiation toward mature osteoblasts, which are characterized by mineralization. In this study, we attempted to identify these secretory proteins during osteogenesis using LC-MS/MS analysis. We compared the secretome between undifferentiated human bone marrow-derived mesenchymal stem cells (hBMSCs) and differentiated osteoblasts. Among 315 proteins that were identified, 177 proteins were present at increased levels in osteoblasts, whereas 88 proteins were present at decreased levels. Among the identified proteins, several were validated by quantitative RT-PCR and immunoblot analysis. Of particular interest, calcium homeostasis-related proteins were upregulated, whereas stem cell proliferation related proteins and other lineage-related proteins were downregulated during osteogenesis. These findings provide information about the dynamic changes in the expression and secretion of proteins during osteogenesis and suggest the putative role of secretory proteins in osteogenesis. PMID- 22674503 TI - Coumarin-based octopamine phototriggers and their effects on an insect octopamine receptor. AB - We have developed and characterized efficient caged compounds of the neurotransmitter octopamine. For derivatization, we introduced [6-bromo-8 (diethylaminomethyl)-7-hydroxycoumarin-4-yl]methoxycarbonyl (DBHCMOC) and {6 bromo-7-hydroxy-8-[(piperazin-1-yl)methyl]coumarin-4-yl}methoxycarbonyl (PBHCMOC) moieties as novel photo-removable protecting groups. The caged compounds were functionally inactive when applied to heterologously expressed octopamine receptors (AmOctalpha1R). Upon irradiation with UV-visible or IR light, bioactive octopamine was released and evoked Ca2+ signals in AmOctalpha1R-expressing cells. The pronounced water solubility of compounds 2-4 in particular holds great promise for these substances as excellent phototriggers of this important neurotransmitter. PMID- 22674504 TI - Taurine chloramine induces apoptosis in human osteosarcoma cell lines. AB - Although combination of surgery with chemotherapy has noticeably improved the survival rate of osteosarcoma patients, the application of anticancer drugs is still associated with significant adverse reactions, for instance acquisition of drug-resistant phenotypes, necessitating the development of new chemotherapeutical agents. Therefore, the aim of this study was to research, if taurine chloramine (NCT) induces apoptosis in the osteosarcoma cell lines HOS, MG 63, and SAOS-2. Proliferation of osteosarcoma cells was detected with the "EZ4U Cell Proliferation and Cyotoxicity Assay" showing a time- and dose-dependent cytotoxic effect of NCT on these cell lines. After 3 h of incubation all cell lines showed significantly less cells at 5.5 mM NCT solutions, after 6 h at concentrations of 1.1 and 2.2 mM. Acridine-orange fluorescence nuclear staining showed characteristic features of apoptosis. DNA fragmentation was detected via ELISA, showing significant results for HOS and MG-63 after 6 h at an NCT concentration of 3.3 mM. Results of JC-1 mitochondrial FACS analysis presented a significant increase in apoptotic cells after 6 h at 3.3 mM for the tested cell lines. Summarized, the results of this study indicate that NCT is a promising agent in osteosarcoma therapy. PMID- 22674505 TI - Chondrocyte-intrinsic Smad3 represses Runx2-inducible matrix metalloproteinase 13 expression to maintain articular cartilage and prevent osteoarthritis. AB - OBJECTIVE: To identify mechanisms by which Smad3 maintains articular cartilage and prevents osteoarthritis. METHODS: A combination of in vivo and in vitro approaches was used to test the hypothesis that Smad3 represses Runx2-inducible gene expression to prevent articular cartilage degeneration. Col2 Cre;Smad3(fl/fl) mice allowed study of the chondrocyte-intrinsic role of Smad3 independently of its role in the perichondrium or other tissues. Primary articular cartilage chondrocytes from Smad3(fl/fl) mice and ATDC5 chondroprogenitor cells were used to evaluate Smad3 and Runx2 regulation of matrix metalloproteinase 13 (MMP-13) messenger RNA (mRNA) and protein expression. RESULTS: Chondrocyte-specific reduction of Smad3 caused progressive articular cartilage degeneration due to imbalanced cartilage matrix synthesis and degradation. In addition to reduced type II collagen mRNA expression, articular cartilage from Col2-Cre;Smad3(fl/fl) mice was severely deficient in type II collagen and aggrecan protein due to excessive MMP-13-mediated proteolysis of these key cartilage matrix constituents. Normally, transforming growth factor beta (TGFbeta) signals through Smad3 to confer a rapid and dynamic repression of Runx2-inducible MMP-13 expression. However, we found that in the absence of Smad3, TGFbeta signals through p38 and Runx2 to induce MMP-13 expression. CONCLUSION: Our findings elucidate a mechanism by which Smad3 mutations in humans and mice cause cartilage degeneration and osteoarthritis. Specifically, Smad3 maintains the balance between cartilage matrix synthesis and degradation by inducing type II collagen expression and repressing Runx2-inducible MMP-13 expression. Selective activation of TGFbeta signaling through Smad3, rather than p38, may help to restore the balance between matrix synthesis and proteolysis that is lost in osteoarthritis. PMID- 22674506 TI - Next generation RNA-sequencing in prognostic subsets of chronic lymphocytic leukemia. AB - Advances in next-generation RNA-sequencing have revealed the complexity of transcriptomes by allowing both coding and noncoding(nc)RNAs to be analyzed. However, limited data exist regarding the whole transcriptional landscape of chronic lymphocytic leukemia(CLL). In this pilot-study, we evaluated RNA sequencing in CLL by comparing two subsets which carry almost identical or "stereotyped" B-cell receptors with distinct clinical outcome, that is the poor prognostic subset #1 (n 5 4) and the more favorable-prognostic subset #4(n 5 4). Our analysis revealed that 156 genes (e.g. LPL, WNT9A) and 76 ncRNAs, (e.g. SNORD48, SNORD115) were differentially expressed between the subsets. This technology also enabled us to identify numerous subset-specific splice variants (n 5 406), which were predominantly expressed in subset #1, including a splice isoform of MSI2 with a novel start exon. A further important application of RNA sequencing was for mutation detection and revealed 16-30 missense mutations per sample; notably many of these changes were found in genes with a strong potential for involvement in CLL pathogenesis, e.g., ATM and NOTCH2.This study not only demonstrates the effectiveness of RNA-sequencing for identifying mutations, quantifying gene expression and detecting splicing events, but also highlights the potential such global approaches have to significantly advance our understanding of the molecular mechanisms behind CLL development. PMID- 22674507 TI - [Aspects of bladder cancer]. PMID- 22674508 TI - [Endourological imaging with narrow band imaging]. AB - Narrow band imaging (NBI) is an optical diagnostic procedure which utilizes the narrowing of the wavelength of visible light in the range between 415 and 550 nm. The NBI is mostly used for the diagnostics of inflammation or tumors of the gastrointestinal tract. The first investigations for diagnostics of bladder cancer using NBI date from 2008. Currently data on resection, follow-up and recurrence behavior of bladder cancer are available. In all publications NBI was tested against white light. A randomized study comparing NBI with photodynamic diagnostics has not yet been carried out. In this article current study results on the application of NBI for bladder cancer will be presented. PMID- 22674509 TI - [Salvage prostatectomy. Principles of diagnostics and operative therapy]. AB - Organ-confined prostate cancer can be treated with curative intent by different types of radiotherapy or by radical surgery. Regardless of improvements in radiotherapy about 60% of patients with prostate cancer develop biochemical recurrence (BCR) which is defined by the progressive increase in serum prostate specific antigen (PSA) and necessitates further diagnostic procedures. If non organ-confined cancer and metastasis are categorically excluded by cross sectional imaging using computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography CT (PET-CT) and bone scintigraphy, a prostate biopsy should be performed. Biopsy proven detection of recurrent or persisting prostate cancer after irradiation is essential prior to a salvage prostatectomy. The function of the lower urinary tract should be evaluated prior to surgery. Preoperative PSA measurement is the best prognostic indicator prior to surgery. Salvage prostatectomy in irradiated patients is more challenging and requires extensive skill. The most common complications are incontinence, rectal injury and anastomotic strictures. Both functional and oncologic outcome have improved due to better irradiation techniques and surgical skills. Provided post radiotherapy recurrence of prostate cancer is diagnosed early enough, curing is possible by salvage prostatectomy. PMID- 22674514 TI - Resurrecting ancient animal genomes: the extinct moa and more. AB - Recently two developments have had a major impact on the field of ancient DNA (aDNA). First, new advances in DNA sequencing, in combination with improved capture/enrichment methods, have resulted in the recovery of orders of magnitude more DNA sequence data from ancient animals. Second, there has been an increase in the range of tissue types employed in aDNA. Hair in particular has proven to be very successful as a source of DNA because of its low levels of contamination and high level of ancient endogenous DNA. These developments have resulted in significant advances in our understanding of recently extinct animals: namely their evolutionary relationships, physiology, and even behaviour. Hair has been used to recover the first complete ancient nuclear genome, that of the extinct woolly mammoth, which then facilitated the expression and functional analysis of haemoglobins. Finally, we speculate on the consequences of these developments for the possibility of recreating extinct animals. PMID- 22674515 TI - The integral role of speech production in the science and treatment of Parkinson's disease. PMID- 22674516 TI - Regulation of early xenopus embryogenesis by Smad ubiquitination regulatory factor 2. AB - BACKGROUND: Smad ubiquitination regulatory factor (Smurf) 1 and 2 are E3 ubiquitin ligases originally identified as inhibitors of transforming growth factor beta signaling and are shown to modulate multiple cellular activities. The roles of Smurfs in vertebrate embryogenesis, however, are not completely understood. RESULTS: Here we investigate the function of Smurf2 during early Xenopus development. We show that distinctly from Smurf1, overexpression of Smurf2 in presumptive mesoderm interfered with mesoderm induction and caused axial defects, whereas knockdown of Smurf2 with antisense morpholino oligonucleotides resulted in expansion of the mesoderm. These results imply that Smurf2 may modulate nodal-mediated mesodermal induction. Consistently, ventral expression of Smurf2 induced a partial secondary axis with head structures. In the ectoderm, Smurf2 resembled Smurf1 in controlling neural and epidermal marker expression and influencing head formation. Smurf1, but not Smurf2, additionally affected neural tube closure. Interestingly, both Smurfs could enhance as well as repress neural crest markers, implying that they modulate their targets dynamically during neural plate border specification. CONCLUSION: Our data demonstrate that Smurf1 and Smurf2 have overlapping and distinct functionalities during early frog embryogenesis; collectively, they regulate ectodermal and mesodermal induction and patterning to ensure normal development of Xenopus embryos. PMID- 22674517 TI - Cognitive performance as a predictor of hepatic encephalopathy in pretransplant patients with cirrhosis receiving psychoactive medications: a prospective study. AB - Psychiatric disorders and medications may affect the cognitive performance of patients with cirrhosis and complicate the diagnosis and prediction of hepatic encephalopathy (HE). The aim of this study was to study the association of psychoactive medications with cognitive performance and their effects on the ability of tests to predict HE development in patients with cirrhosis referred for transplant evaluation. Cirrhosis details, psychiatric disorders, psychoactive medications, and any history of prior HE were recorded for patients with cirrhosis at 2 transplant centers. Patients were followed until the development of HE. Five cognitive tests--number connection test A (NCT-A), number connection test B, the digit symbol test (DST), the block design test, and the inhibitory control test (ICT)--were administered. A high lure score and a low ICT target score indicated poor performance. The cognitive performances of patients with psychiatric disorders/medications and patients without them were compared. A proportional hazards model was created with the time to HE as the outcome, and it was based on demographics, psychoactive medications, cirrhosis details, and individual cognitive scores. Patients with prior HE and patients without prior HE were then studied separately. One hundred fifty-five patients with a mean age of 57.5 +/- 6.2 years and a mean Model for End-Stage Liver Disease (MELD) score of 15.1 +/- 6.2 were included [prior HE, 48%; diabetes, 34%; selective serotonin reuptake inhibitors (SSRIs), 32%; opioids, 19%; and antipsychotics, 10%]. Prior HE and antipsychotics (but not opioids or diabetes) were associated with worse cognition. SSRI users had better NCT-A and DST performance. One hundred forty eight patients were followed for a median of 182.5 days; 58 developed HE at a median of 99 days after inclusion. In the entire group, the model showed that prior HE (hazard ratio = 4.13), the MELD score (hazard ratio = 1.07), and a high lure score (hazard ratio = 1.04) decreased the time to HE, whereas the use of SSRIs (hazard ratio = 0.42), a high target score (hazard ratio = 0.95), and a high sodium level (hazard ratio = 0.89) increased the time to HE. For patients without prior HE, the MELD score (hazard ratio = 1.25) and lures (hazard ratio = 1.09) predicted the time to HE. Lures (hazard ratio = 1.03), targets (hazard ratio = 0.96), and sodium (hazard ratio = 0.87) were associated with the time to HE in patients with prior HE. In conclusion, cognitive tests (particularly the ICT) remain valid predictors of HE in the face of psychiatric diseases and medications. SSRI use is associated with better cognitive performance and a reduced likelihood of developing HE. PMID- 22674518 TI - Solution-processable pyrite FeS(2) nanocrystals for the fabrication of heterojunction photodiodes with visible to NIR photodetection. AB - A heterojunction photodiode with NIR photoresponse using solution processable pyrite FeS(2) nanocrystal ink is demonstrated which has the advantages of earth abundance and non-toxicity. The device consists of a FeS(2) nanocrystal (NC) thin film sandwiched with semiconducting metal oxides with a structure of ITO/ZnO/FeS(2) NC/MoO(3) /Au, which exhibits an excellent photoresponse with a spectral response extended to NIR wavelengths of up to 1150 nm and a high photocurrent/dark current ratio of up to 8000 at -1 V under AM1.5 illumination (100 mW cm(-2) ). PMID- 22674519 TI - An acid-catalyzed cyclialkylation that provides rapid access to a twisted molecular basket. PMID- 22674520 TI - Self-assembled magnetic bead biosensor for measuring bacterial growth and antimicrobial susceptibility testing. AB - Bacterial antibiotic resistance is one of the major concerns of modern healthcare worldwide, and the development of rapid, growth-based, antimicrobial susceptibility tests is key for addressing it. The cover image shows a self assembled asynchronous magnetic bead rotation (AMBR) biosensor developed for rapid detection of bacterial growth. Using the biosensors, the minimum inhibitory concentration of a clinical E. coli isolate can be measured within two hours, where currently tests take 6-24 hours. A 16-well prototype is also constructed for simple and robust observation of the self-assembled AMBR biosensors. PMID- 22674523 TI - Lithiated porous aromatic frameworks with exceptional gas storage capacity. PMID- 22674524 TI - The hunt for gene effects pertinent to behavioral traits and psychiatric disorders: from mouse to human. AB - The field of behavioral genetics was reviewed in the classic 1960 text by Fuller and Thompson. Since then, there has been remarkable progress in the genetic analysis of animal behavior. Many molecular genetic methods in common use today were not even anticipated in 1960. Animal models for many human psychiatric disorders have been discovered or created. In human behavior genetics, however, powerful new methods have failed to reveal even one bona fide, replicable gene effect pertinent to the normal range of variation in intelligence and personality. There is no explanatory or predictive value in that genetic information. For several psychiatric disorders, including autism and schizophrenia, many large genetic effects arise from de novo mutations. Genetically, the disorders are heterogeneous; different cases with the same diagnosis have different causes. The promises of the molecular genetic revolution have not been fulfilled in behavioral domains of most interest to human psychology. PMID- 22674527 TI - Iron resonant photoemission spectroscopy on anodized hematite points to electron hole doping during anodization. AB - Anodization of alpha-Fe(2)O(3) (hematite) electrodes in alkaline electrolyte under constant potential conditions the electrode surface in a way that an additional current wave occurs in the cyclic voltammogram. The energy position of this current wave is closely below the potential of the anodization treatment. Continued cycling or exchanging of the electrolyte causes depletion of this new feature. The O 1s and Fe 2p core-level X-ray photoelectron spectra (XPS) and near edge X-ray absorption fine structure (NEXAFS) spectra of such conditioned hematite exhibit a chemical shift towards higher binding energies, in line with the general perception that anodization generates oxide species with dielectric properties. The valence band XPS and particularly the iron resonant valence band photoemission spectra, however, are shifted towards the opposite direction, that is, towards the Fermi energy, suggesting that hole doping on hematite has taken place during anodization. Quantitative analysis of the Fe 2p resonant valence band photoemission spectra shows that the spectra obtained at the Fe 2p absorption threshold are shifted by virtually the same energy as the anodization potential towards the Fermi energy. The tentative interpretation of this observation is that anodization forms a surface film on the hematite that is specific to the anodization potential. PMID- 22674528 TI - Molecular and organismal changes in offspring of male mice treated with chemical stressors. AB - Both gene methylation changes and genetic instability have been noted in offspring of male rodents exposed to radiation or chemicals, but few specific gene targets have been established. Previously, we identified the gene for ribosomal RNA, rDNA, as showing methylation change in sperm of mice treated with the preconceptional carcinogen, chromium(III) chloride. rDNA is a critical cell growth regulator. Here, we investigated the effects of paternal treatments on rDNA in offspring tissue. A total of 93 litters and 758 offspring were obtained, permitting rigorous mixed-effects models statistical analysis of the results. We show that the offspring of male mice treated with Cr(III) presented increased methylation in a promoter sequence of the rDNA gene, specifically in lung. Furthermore polymorphic variants of the multi-copy rDNA genes displayed altered frequencies indicative of structural changes, as a function of both tissue type and paternal treatments. Organismal effects also occurred: some groups of offspring of male mice treated with either Cr(III) or its vehicle, acidic saline, compared with those of untreated mice, had altered average body and liver weights and levels of serum glucose and leptin. Males treated directly with Cr(III) or acidic saline presented serum hormone changes consistent with a stress response. These results establish for the first time epigenetic and genetic instability effects in a gene of central physiological importance, in offspring of male mice exposed preconceptionally to chemicals, possibly related to a stress response in these males. PMID- 22674529 TI - A phase 3 study of induction treatment with concurrent chemoradiotherapy versus chemotherapy before surgery in patients with pathologically confirmed N2 stage IIIA nonsmall cell lung cancer (WJTOG9903). AB - BACKGROUND: This study sought to ascertain whether induction-concurrent radiotherapy added to chemotherapy could improve the survival of patients undergoing surgery for stage IIIA N2 nonsmall cell lung cancer (NSCLC). METHODS: Patients with pathologically proven N2 disease were randomized to receive either induction chemotherapy (docetaxel 60 mg/m(2) and carboplatin AUC [area under the receiver operating characteristic curve] = 5 for 2 cycles) plus concurrent radiation therapy (40 Gy) followed by surgery (CRS arm) or induction chemotherapy followed by surgery (CS arm). They subsequently underwent pulmonary resection when possible. RESULTS: Sixty patients were randomly assigned between December 2000 and August 2005. The study was prematurely terminated in January 2006 because of slow accrual. The most common toxicity was grade 3 or 4 leukopenia in 92.9% of patients in the CRS arm and 46.4% in the CS arm. Induction therapy was generally well tolerated, and there were no treatment-related deaths in either arm. Downstaging in the CS arm and CRS arm was 21% and 40%, respectively. The progression-free survival (PFS) and overall survival (OS) in the CS arm were 9.7 months and 29.9 months (PFS, hazard ratio [HR] = 0.68, P = .187), and those in the CRS arm were 12.4 months and 39.6 months (OS, HR = 0.77, P = .397), respectively. The PFS with and without downstaging was 55.0 and 9.4 months, respectively (HR = 3.39, P = .001). The OS with and without downstaging was 63.3 and 29.5 months, respectively (HR = 2.62, P = .021). CONCLUSIONS: The addition of radiotherapy to induction chemotherapy conferred better local control without significant adverse events. Tumor downstaging is important for prolonging the OS in patients with stage IIIA (N2) NSCLC. PMID- 22674530 TI - Inorganic phosphate enhances sensitivity of human osteosarcoma U2OS cells to doxorubicin via a p53-dependent pathway. AB - Osteosarcoma is the most common malignant primary bone tumor in children and adolescents. The clinical outcome for osteosarcoma remains discouraging despite aggressive surgery and intensive radiotherapy and chemotherapy regimens. Thus, novel therapeutic approaches are needed. Previously, we have shown that inorganic phosphate (Pi) inhibits proliferation and aggressiveness of human osteosarcoma U2OS cells identifying adenylate cyclase, beta3 integrin, Rap1, ERK1/2 as proteins whose expression and function are relevantly affected in response to Pi. In this study, we investigated whether Pi could affect chemosensitivity of osteosarcoma cells and the underlying molecular mechanisms. Here, we report that Pi inhibits proliferation of p53-wild type U2OS cells (and not of p53-null Saos and p53-mutant MG63 cells) by slowing-down cell cycle progression, without apoptosis occurrence. Interestingly, we found that Pi strongly enhances doxorubicin-induced cytotoxicity in U2OS, and not in Saos and MG63 cells, by apoptosis induction, as revealed by a marked increase of sub-G1 population, Bcl-2 downregulation, caspase-3 activation, and PARP cleavage. Remarkably, Pi/doxorubicin combination-induced cytotoxicity was accompanied by an increase of p53 protein levels and of p53 target genes mdm2, p21 and Bax, and was significantly reduced by the p53 inhibitor pifithrine-alpha. Moreover, the doxorubicin-induced cytotoxicity was associated with ERK1/2 pathway inhibition in response to Pi. Altogether, our data enforce the evidence of Pi as a novel signaling molecule capable of inhibiting ERK pathway and inducing sensitization to doxorubicin of osteosarcoma cells by p53-dependent apoptosis, implying that targeting Pi levels might represent a rational strategy for improving osteosarcoma therapy. PMID- 22674531 TI - CD133 expression is correlated with chemoresistance and early recurrence of gastric cancer. AB - BACKGROUND: CD133 has been suggested to be a cancer stem cell (CSC) marker in various types of cancers. The present study assessed the relationship between CD133 expression and clinicopathological features of gastric cancer. In addition, the prognostic value of CD133 for gastric cancer was evaluated. METHODS: In total, 100 advanced gastric cancer patients who received curative gastrectomy and adjuvant chemotherapy were included. CD133 expression was determined by immunohistochemistry and clinicopathological results, including survival, were analyzed. RESULTS: CD133 was expressed in 23% of advanced gastric cancer patients (23/100). CD133 expression was significantly associated with serosal exposure (P = 0.036), venous invasion (P = 0.047), well and moderate differentiation (P = 0.002), and intestinal-type Lauren classification (P = 0.001). CD133-positive patients had a significantly worse 5-year disease-free (28.1% vs. 65.8%, P = 0.002) and overall (47.5% vs. 74.0%, P = 0.037) survival rate than those who were CD133-negative. A multivariate analysis suggested that CD133 expression significantly affected the 5-year disease-free and overall survival. CONCLUSIONS: CD133 may play an important role in chemoresistance and recurrence, thus representing a promising predictive marker for the prognosis of gastric cancer. PMID- 22674532 TI - Risk of superficial squamous cell carcinoma developing in the head and neck region in patients with esophageal squamous cell carcinoma. AB - OBJECTIVES/HYPOTHESIS: Multicentric squamous dysplasia in the esophagus can be visualized by Lugol chromoendoscopy as multiple Lugol-voiding lesions (LVLs). Narrow-band imaging combined with magnifying endoscopy (NBI-ME) facilitates the detection of superficial squamous cell carcinoma within the head and neck region (HNSCC). We investigated risk factors for superficial HNSCC in patients with esophageal squamous cell carcinoma (ESCC). STUDY DESIGN: Case-control study. METHODS: We studied 71 patients with synchronous or former ESCC. All patients underwent screening of the head and neck by NBI-ME and Lugol chromoendoscopy of the esophageal mucosa. The history of tobacco and alcohol use was documented. Genetic polymorphisms of aldehyde dehydrogenase type 2 (ALDH2) were identified by the sequence-specific primer polymerase chain reaction. Clinical factors related to superficial HNSCC were analyzed. RESULTS: All patients with superficial HNSCC were drinkers. On univariate analysis, multiple LVLs (odds ratio [OR], 56.92; 95% confidence interval [CI] 6.93-467.38; P < .001), ALDH2-2 allele (OR, 14.48; 95% CI, 1.8-116.56; P = .01), current smoker (OR, 4.25; 95% CI, 1.44-12.57; P = .009), and smoking index >= 1,000 (OR, 3.45; 95% CI, 1.19-9.99; P = .02) were associated with superficial HNSCC. On multivariate analysis, multiple LVLs (OR, 61.12; 95% CI, 5.4-691.64; P = .001), ALDH2-2 allele (OR, 16.19; 95% CI, 1.15 228.06; P = .04), and current smoker (OR, 8.02; 95% CI, 1.09-59.22; P = .04) were associated with superficial HNSCC. CONCLUSIONS: Patients with ESCC, particularly drinkers, current smokers, and those with the ALDH2-2 allele and multiple LVLs, have an increased risk of superficial HNSCC. PMID- 22674533 TI - Inducible immortality in hTERT-human mesenchymal stem cells. AB - Human mesenchymal stem cells (hMSCs) are attractive candidates for tissue engineering and cell-based therapy because of their multipotentiality and availability in adult donors. However, in vitro expansion and differentiation of these cells is limited by replicative senescence. The proliferative capacity of hMSCs can be enhanced by ectopic expression of telomerase, allowing for long-term culture. However, hMSCs with constitutive telomerase expression demonstrate unregulated growth and even tumor formation. To address this problem, we used an inducible Tet-On gene expression system to create hMSCs in which ectopic telomerase expression can be induced selectively by the addition of doxycycline (i-hTERT hMSCs). i-hTERT hMSCs have inducible hTERT expression and telomerase activity, and are able to proliferate significantly longer than wild type hMSCs when hTERT expression is induced. They stop proliferating when hTERT expression is turned off and can be rescued when expression is re-induced. They retain multipotentiality in vitro even at an advanced age. We also used a selective inhibitor of telomere elongation to show that the mechanism driving immortalization of hMSCs by hTERT is dependent upon maintenance of telomere length. Thanks to their extended lifespan, preserved multipotentiality and controlled growth, i-hTERT hMSCs may prove to be a useful tool for the development and testing of novel stem cell therapies. PMID- 22674534 TI - Portopulmonary hypertension: an update. AB - Portopulmonary hypertension (POPH) is a serious complication of cirrhosis that is associated with mortality beyond that predicted by the Model for End-Stage Liver Disease (MELD) score. Increased pulmonary vascular resistance (PVR) may be initiated by pulmonary vasoconstriction, altered levels of circulating mediators, or shear stress, and can eventually lead to the classic vascular remodeling (plexiform lesion) that characterizes POPH. Portal hypertension is a prerequisite for the diagnosis of POPH, although the severity of pulmonary hypertension is unrelated to the severity of portal hypertension or the nature or severity of liver disease. POPH precludes liver transplantation (LT) unless the mean pulmonary artery pressure (MPAP) can be reduced to a safe level. The concept of an acceptable pressure has changed: we now consider both MPAP and PVR in the diagnosis, and we include the transpulmonary pressure gradient so that we can factor in fluid overload and left ventricular failure. Pulmonary vasodilator therapy includes oral, inhaled, and parenteral agents, and one or more of these agents may significantly lower pulmonary artery pressures to the point that LT becomes possible. The United Network for Organ Sharing recommends MELD exception points for patients with medically controlled POPH, but this varies by region. Patients who undergo LT need specialized intraoperative and postoperative management, which includes the availability of intraoperative transesophageal echocardiography for assessing right ventricular function, and rapidly acting vasodilators (eg, inhaled nitric oxide and/or epoprostenol). Published case series suggest excellent outcomes after LT for patients who respond to medical therapy. PMID- 22674536 TI - Does patient age impact outcomes of neuromodulation? AB - AIMS: We evaluated whether patients stratified by age have the same level of risks/benefits after a staged neuromodulation procedure for refractory voiding symptoms. METHODS: Urologic diagnosis, complications, and revisions were collected from medical records of adults enrolled in our prospective observational study. Symptoms were assessed over 2 years with diaries, Interstitial Symptom-Problem Indices (ICSI-PI), and the Overactive Bladder Questionnaire-SF (OAB-q SF). 12-item Short-Form Health Survey (SF-12v2(r)) mental (MCS) and physical (PCS) component summaries evaluated quality of life. Data were examined with Pearson Chi-square or Fisher's Exact test, Kruskal-Wallis tests, and repeated measures analyses. RESULTS: Patients (83% female) were grouped by age (years): <40 (n = 46), 40-64 (n = 146), and >=65 (n = 136). Urge incontinence was predominant in the older groups and more patients <40 had interstitial cystitis/painful bladder syndrome (IC/PBS). In the <40, 40-64, and >=65 groups, respectively, generator implant (91%, 88%, and 89%) and explant (15%, 12%, and 10%) rates were similar. Complications (24%, 14%, and 9%; P = 0.031) and revisions (20%, 5%, and 6%; P = 0.0025) differed. For the three respective groups, urinary frequency (P < 0.0001 for all), nocturia (P < 0.0001 for all), incontinence episodes (P < 0.0001 for all), urgency (P = 0.0474, P < 0.0001, P = 0.0020), ICSI-PI (P = 0.0015, P < 0.0001, P < 0.0001), and OAB-q scores improved over time. Incontinence severity improved in those >65 (P = 0.0015). SF-12 PCS improved in those 40-64 (P = 0.0482) and MCS scores improved in the <40 and 40-64 age groups (P = 0.013 and P = 0.0440, respectively). CONCLUSIONS: These data suggest that neuromodulation success is not age dependent, however continued study is needed to confirm findings. PMID- 22674535 TI - Biallelic expression of Tbx1 protects the embryo from developmental defects caused by increased receptor tyrosine kinase signaling. AB - BACKGROUND: 22q11.2 deletion syndrome (22q11DS) is the most common microdeletion syndrome in humans, characterized by cardiovascular defects such as interrupted aortic arch, outflow tract defects, thymus and parathyroid hypo- or aplasia, and cleft palate. Heterozygosity of Tbx1, the mouse homolog of the candidate TBX1 gene, results in mild defects dependent on genetic background, whereas complete inactivation results in severe malformations in multiple tissues. RESULTS: The loss of function of two Sprouty genes, which encode feedback antagonists of receptor tyrosine kinase (RTK) signaling, phenocopy many defects associated with 22q11DS in the mouse. The stepwise reduction of Sprouty gene dosage resulted in different phenotypes emerging at specific steps, suggesting that the threshold up to which a given developmental process can tolerate increased RTK signaling is different. Tbx1 heterozygosity significantly exacerbated the severity of all these defects, which correlated with a substantial increase in RTK signaling. CONCLUSIONS: Our findings suggest that TBX1 functions as an essential component of a mechanism that protects the embryo against perturbations in RTK signaling that may lead to developmental defects characteristic of 22q11DS. We propose that genetic factors that enhance RTK signaling ought to be considered as potential genetic modifiers of this syndrome. PMID- 22674537 TI - Highly dispersed pd catalyst locked in knitting aryl network polymers for Suzuki Miyaura coupling reactions of aryl chlorides in aqueous media. AB - Highly dispersed palladium chloride catalysts locked in triphenylphosphine functionalized knitting aryl network polymers (KAPs) are developed and exhibit excellent activity under mild conditions in the Suzuki-Miyaura cross-coupling reactions of aryl chlorides in aqueous media. This work highlights that the microporous polymers not only play the role of support materials, but also protect the Pd species from aggregation and precipitation, hence, positively effect the catalysis activity. PMID- 22674538 TI - Analyzing transformation of myelodysplastic syndrome to secondary acute myeloid leukemia using a large patient database. AB - One-third of patients with myelodysplastic syndrome (MDS) progress to secondary acute myeloid leukemia (sAML), with its concomitant poor prognosis. Recently, multiple mutations have been identified in association with MDS-to sAMLtransition, but it is still unclear whether all these mutations are necessary for transformation. If multiple independent mutations are required for the transformation, sAML risk should increase with time from MDS diagnosis. In contrast, if a single critical biological event determines sAML transformation; its risk should be constant in time elapsing from MDS diagnosis. To elucidate this question, we studied a database of 1079 patients with MDS. We classified patients according to the International Prognostic Scoring System (IPSS), using either the French-American-British (FAB) or the World Health Organization (WHO) criteria, and statistically analyzed the resulting transformation risk curves of each group. The risk of transformation after MDS diagnosis remained constant in time within three out of four risk groups, and in all four risk groups, when patients were classified according to FAB or to the WHO-determined criteria, respectively. Further subdivision by blast percentage or cytogenetics had no influence on this result. Our analysis suggests that a single random biological event leads to transformation to sAML, thus calling for the exclusion of time since MDS diagnosis from the clinical decision-making process. PMID- 22674539 TI - The development of effective biomarkers for Alzheimer's disease: a review. AB - OBJECTIVE: There is a widely recognised need to develop effective Alzheimer's disease (AD) biomarkers to aid the development of disease-modifying treatments, to facilitate early diagnosis and to improve clinical care. This overview aims to summarise the utility of key neuroimaging and cerebrospinal fluid (CSF) biomarkers for AD, before focusing on the latest efforts to identify informative blood biomarkers. DESIGN: A literature search was performed using PubMed up to September 2011 for reviews and primary research studies of neuroimaging (magnetic resonance imaging, magnetic resonance spectroscopy, positron emission tomography and amyloid imaging), CSF and blood-based (plasma, serum and platelet) biomarkers in AD and mild cognitive impairment. Citations within individual articles were examined to identify additional studies relevant to this review. RESULTS: Evidence of AD biomarker potential was available for imaging techniques reflecting amyloid burden and neurodegeneration. Several CSF measures are promising, including 42 amino acid beta-amyloid peptide (Abeta42 ); total tau (T tau) protein, reflecting axonal damage; and phosphorylated tau (P-tau), reflecting neurofibrillary tangle pathology. Studies of plasma Abeta have produced inferior diagnostic discrimination. Alternative plasma and platelet measures are described, which represent potential avenues for future research. CONCLUSIONS: Several imaging and CSF markers demonstrate utility in predicting AD progression and determining aetiology. These require standardisation before forming core elements of diagnostic criteria. The enormous potential available for identifying a minimally-invasive, easily-accessible blood measure as an effective AD biomarker currently remains unfulfilled. PMID- 22674540 TI - Patterning of crystalline organic materials by electro-hydrodynamic lithography. AB - The control of semi-crystalline polymers in thin films and in micrometer-sized patterns is attractive for (opto-)electronic applications. Electro-hydrodynamic lithography (EHL) enables the structure formation of organic crystalline materials on the micrometer length scale while at the same time exerting control over crystal orientation. This gives rise to well-defined micro-patterned arrays of uniaxially aligned polymer crystals. This study explores the interplay of EHL structure formation with crystal alignment and studies the mechanisms that give rise to crystal orientation in EHL-generated structures. PMID- 22674541 TI - Cationic gallium(III) halide complexes: a new generation of pi-Lewis acids. PMID- 22674542 TI - The hippocampal physiology of approaching middle-age: early indicators of change. AB - Age-related cognitive decline presents serious lifestyle challenges, and anatomical changes to the hippocampus are often implicated in clinical conditions later in life. However, relatively little is known about how hippocampal physiology is altered in the transition to middle-age, when early detection may offer the best opportunity for successful treatment. High-yield extracellular recording is a powerful tool for understanding brain function in freely moving animals at single-cell resolution and with millisecond precision. We used this technique to characterize changes to hippocampal physiology associated with maturation in 35-week-old rats. Combining a series of behavioral tasks with recordings of large numbers of neurons, local field potentials (LFP), and network patterns of activation, we were able to generate a comprehensive picture based on more than 25 different assays for each subject. Notable changes associated with aging included increased firing rates in interneurons, reduced LFP power but increased frequency in the 4-12 Hz theta band, and impairment in hippocampal pattern-separation for different environments. General properties of pyramidal cell firing and spatial map integrity were preserved. There was no impairment in theta phase-precession, experience-dependent place field expansion, or sleep reactivation of waking network patterns. There were however changes in foraging strategy and behavioral responses to the introduction of a novel environment. Taken together the results reveal a diverse pattern of changes which are of increasing relevance in an aging population. They also highlight areas where high yield electrophysiological assays can be used to provide the sensitivity and throughput required for pre-clinical drug-discovery programs. PMID- 22674543 TI - Longevity and the long arm of epigenetics: acquired parental marks influence lifespan across several generations. AB - A recent study reported that longevity in Caenorhabditits elegans can be inherited over several generations. This is probably achieved through the following epigenetic mechanism: inherited demethylated histones at some central loci, such as miRNA, transcription factors or signaling regulators affect the expression of certain genes leading to the longevity phenotype. PMID- 22674544 TI - Effects of different types of contingent tactile stimulation on crying, smiling, and sleep in newborns: an observational study. AB - Sleep, the brain and the ability to interact with the environment change a great deal over the first year of life; however, there are no studies on the possible influence of different environmental stimulations on the organization of subsequent sleep-wake cycles in infants. The hypothesis of this study was that greater continuity of contingent tactile stimulation decreases crying behavior, subsequent active sleep (AS) and its fragmentation, and increases smiling behavior and subsequent quiet sleep in newborns. Forty out of the 82 newborns (15 to 30-hr old) of the initial sample satisfied the inclusion criteria and completed the first cycle of sleep during the period between two feedings. The 40 newborns were randomly assigned to four groups after 2' of baseline observation: continuous stimulation (CS, n = 10); discontinuous nonperiodic stimulation (DnPS, n = 10); discontinuous periodic stimulation (DPS, n = 10); absent stimulation (AbS, n = 10). During baseline measurements, there were no significant differences in crying and smiling behaviors between the four groups, while during the subsequent stimulated wake, the CS group compared to the DnPS group showed more smiling (p < .05) and less crying (p < .05), longer poststimulation wake before sleep (p < .01) as well as AS with a lower percentage of grouped-rapid eye movements [grouped REM (GREM); p < .001]. The number of GREM during AS was negatively correlated to the number of smiles (p < .05) and positively to the number of cries (p < .05) of the previous stimulated wake. These findings suggest that, after birth, different continuity levels of contingent tactile stimulations may affect crying and smiling behaviors and the organization of behavioral states. AS could have an important role in processing affective states. PMID- 22674545 TI - Chirality transfer and memory of chirality in gold-catalyzed reactions. AB - Over the last few years, gold-catalyzed reactions that involved chirality transfer and memory of chirality (MOC) have emerged as a powerful tool in enantioselective synthesis. This technique has allowed for the single-step synthesis of enantioenriched compounds from readily available starting materials. This Focus Review discusses this emerging field with an emphasis on mechanistic aspects and their applications in synthetic organic chemistry. PMID- 22674546 TI - Surgical approaches to gastric cancer. AB - While the incidence of gastric cancer has declined substantially, it remains a major cause of morbidity and mortality. Surgical resection offers the best chance for curative treatment. Despite numerous studies, surgical controversies persist including endoscopic resection, extent of gastric resection, degree of lymphadenectomy, and laparoscopic resection. Balancing the benefits with the risks of surgical morbidity and mortality is essential. This review examines these controversies and provides insight into the surgical management of gastric cancer. PMID- 22674547 TI - DNA damage profiles induced by sunlight at different latitudes. AB - Despite growing knowledge on the biological effects of ultraviolet (UV) radiation on human health and ecosystems, it is still difficult to predict the negative impacts of the increasing incidence of solar UV radiation in a scenario of global warming and climate changes. Hence, the development and application of DNA-based biological sensors to monitor the solar UV radiation under different environmental conditions is of increasing importance. With a mind to rendering a molecular view-point of the genotoxic impact of sunlight, field experiments were undertaken with a DNA-dosimeter system in parallel with physical photometry of solar UVB/UVA radiation, at various latitudes in South America. On applying biochemical and immunological approaches based on specific DNA-repair enzymes and antibodies, for evaluating sunlight-induced DNA damage profiles, it became clear that the genotoxic potential of sunlight does indeed vary according to latitude. Notwithstanding, while induction of oxidized DNA bases is directly dependent on an increase in latitude, the generation of 6-4PPs is inversely so, whereby the latter can be regarded as a biomolecular marker of UVB incidence. This molecular DNA lesion-pattern largely reflects the relative incidence of UVA and UVB energy at any specific latitude. Hereby is demonstrated the applicability of this DNA based biosensor for additional, continuous field experiments, as a means of registering variations in the genotoxic impact of solar UV radiation. PMID- 22674548 TI - FOXP3 expression in tumor cells and implications for cancer progression. AB - FOXP3 is a member of the forkhead/winged-helix family of transcriptional regulators. Defects in the FOXP3 gene cause an X-linked autoimmune/immunodeficiency syndrome in humans and the Scurfy phenotype in mice. FOXP3 acts mainly in regulating the development and function of CD4+CD25+ regulatory T cells. Although initially thought to be specific for these cells, FOXP3 expression has recently been described in non-hematopoietic cells, including epithelial cells of multiple lineages and of different tissue origins. Moreover, FOXP3 expression has been detected in tumor cells of both epithelial and non-epithelial tissues. The role of FOXP3 expression by tumor cells remains controversial, with in vitro studies pointing to an onco-suppressive action, whereas studies conducted on human samples associate FOXP3 expression by tumor cells with metastatic spread. Here, we review evidence for the multi-faceted role of FOXP3 in cancer cells. PMID- 22674549 TI - The human gut microbiota and undernutrition. AB - Childhood malnutrition is a global health problem that cannot be attributed to food insecurity alone. The gut microbiota may contribute to this devastating health disorder. In this Perspective, we call for the application of tools and concepts emerging from studies of the human gut microbiota to better understand the nutritional needs of infants and children and the role of the microbiota in the pathogenesis and treatment of undernutrition. This effort will require elucidation of the interrelationships between breast milk composition and the development of the microbiota and immune system in the context of the maternal infant dyad. PMID- 22674550 TI - Preexisting BCG-specific T cells improve intravesical immunotherapy for bladder cancer. AB - Therapeutic intravesical instillation of bacillus Calmette-Guerin (BCG) is effective at triggering inflammation and eliciting successful tumor immunity in patients with non-muscle invasive bladder cancer, with 50 to 70% clinical response. Therapeutic success relies on repeated instillations of live BCG administered as adjuvant therapy shortly after tumor resection; however, the precise mechanisms remain unclear. Using an experimental model, we demonstrate that after a single instillation, BCG could disseminate to bladder draining lymph nodes and prime interferon-gamma-producing T cells. Nonetheless, repeated instillations with live BCG were necessary for a robust T cell infiltration into the bladder. Parenteral exposure to BCG before instillation overcame this requirement; after the first intravesical instillation, BCG triggered a more robust acute inflammatory process and accelerated T cell entry into the bladder, as compared to the standard protocol. Moreover, parenteral exposure to BCG before intravesical treatment of an orthotopic tumor markedly improved response to therapy. Indeed, patients with sustained preexisting immunity to BCG showed a significant improvement in recurrence-free survival. Together, these data suggest that monitoring patients' response to purified protein derivative, and, in their absence, boosting BCG responses by parenteral exposure before intravesical treatment initiation, may be a safe and effective means of improving intravesical BCG-induced clinical responses. PMID- 22674551 TI - Identification of naturally occurring fatty acids of the myelin sheath that resolve neuroinflammation. AB - Lipids constitute 70% of the myelin sheath, and autoantibodies against lipids may contribute to the demyelination that characterizes multiple sclerosis (MS). We used lipid antigen microarrays and lipid mass spectrometry to identify bona fide lipid targets of the autoimmune response in MS brain, and an animal model of MS to explore the role of the identified lipids in autoimmune demyelination. We found that autoantibodies in MS target a phosphate group in phosphatidylserine and oxidized phosphatidylcholine derivatives. Administration of these lipids ameliorated experimental autoimmune encephalomyelitis by suppressing activation and inducing apoptosis of autoreactive T cells, effects mediated by the lipids' saturated fatty acid side chains. Thus, phospholipids represent a natural anti inflammatory class of compounds that have potential as therapeutics for MS. PMID- 22674552 TI - Phase 1 study of stereotactic body radiotherapy and interleukin-2--tumor and immunological responses. AB - Preclinical models suggest that focal high-dose radiation can make tumors more immunogenic. We performed a pilot study of stereotactic body radiation therapy (SBRT) followed by high-dose interleukin-2 (IL-2) to assess safety and tumor response rate and perform exploratory immune monitoring studies. Patients with metastatic melanoma or renal cell carcinoma (RCC) who had received no previous medical therapy for metastatic disease were eligible. Patients received one, two, or three doses of SBRT (20 Gy per fraction) with the last dose administered 3 days before starting IL-2. IL-2 (600,000 IU per kilogram by means of intravenous bolus infusion) was given every 8 hours for a maximum of 14 doses with a second cycle after a 2-week rest. Patients with regressing disease received up to six IL 2 cycles. Twelve patients were included in the intent-to-treat analysis, and 11 completed treatment per the study design. Response Evaluation Criteria in Solid Tumors criteria were used to assess overall response in nonirradiated target lesions. Eight of 12 patients (66.6%) achieved a complete (CR) or partial response (PR) (1 CR and 7 PR). Six of the patients with PR on computed tomography had a CR by positron emission tomography imaging. Five of seven (71.4%) patients with melanoma had a PR or CR, and three of five (60%) with RCC had a PR. Immune monitoring showed a statistically significantly greater frequency of proliferating CD4(+) T cells with an early activated effector memory phenotype (CD3(+)CD4(+)Ki67(+)CD25(+)FoxP3(-)CCR7(-)CD45RA(-)CD27(+)CD28(+/-)) in the peripheral blood of responding patients. SBRT and IL-2 can be administered safely. Because the response rate in patients with melanoma was significantly higher than expected on the basis of historical data, we believe that the combination and investigation of CD4(+) effector memory T cells as a predictor of response warrant further study. PMID- 22674554 TI - Noninvasive whole-genome sequencing of a human fetus. AB - Analysis of cell-free fetal DNA in maternal plasma holds promise for the development of noninvasive prenatal genetic diagnostics. Previous studies have been restricted to detection of fetal trisomies, to specific paternally inherited mutations, or to genotyping common polymorphisms using material obtained invasively, for example, through chorionic villus sampling. Here, we combine genome sequencing of two parents, genome-wide maternal haplotyping, and deep sequencing of maternal plasma DNA to noninvasively determine the genome sequence of a human fetus at 18.5 weeks of gestation. Inheritance was predicted at 2.8 * 10(6) parental heterozygous sites with 98.1% accuracy. Furthermore, 39 of 44 de novo point mutations in the fetal genome were detected, albeit with limited specificity. Subsampling these data and analyzing a second family trio by the same approach indicate that parental haplotype blocks of ~300 kilo-base pairs combined with shallow sequencing of maternal plasma DNA is sufficient to substantially determine the inherited complement of a fetal genome. However, ultradeep sequencing of maternal plasma DNA is necessary for the practical detection of fetal de novo mutations genome-wide. Although technical and analytical challenges remain, we anticipate that noninvasive analysis of inherited variation and de novo mutations in fetal genomes will facilitate prenatal diagnosis of both recessive and dominant Mendelian disorders. PMID- 22674553 TI - A validated tumorgraft model reveals activity of dovitinib against renal cell carcinoma. AB - Most anticancer drugs entering clinical trials fail to achieve approval from the U.S. Food and Drug Administration. Drug development is hampered by the lack of preclinical models with therapeutic predictive value. Herein, we report the development and validation of a tumorgraft model of renal cell carcinoma (RCC) and its application to the evaluation of an experimental drug. Tumor samples from 94 patients were implanted in the kidneys of mice without additives or disaggregation. Tumors from 35 of these patients formed tumorgrafts, and 16 stable lines were established. Samples from metastatic sites engrafted at higher frequency than those from primary tumors, and stable engraftment of primary tumors in mice correlated with decreased patient survival. Tumorgrafts retained the histology, gene expression, DNA copy number alterations, and more than 90% of the protein-coding gene mutations of the corresponding tumors. As determined by the induction of hypercalcemia in tumorgraft-bearing mice, tumorgrafts retained the ability to induce paraneoplastic syndromes. In studies simulating drug exposures in patients, RCC tumorgraft growth was inhibited by sunitinib and sirolimus (the active metabolite of temsirolimus in humans), but not by erlotinib, which was used as a control. Dovitinib, a drug in clinical development, showed greater activity than sunitinib and sirolimus. The routine incorporation of models recapitulating the molecular genetics and drug sensitivities of human tumors into preclinical programs has the potential to improve oncology drug development. PMID- 22674555 TI - Microbiota-targeted therapies: an ecological perspective. AB - The connection between disease and the disruption of homeostatic interactions between the host and its microbiota is now well established. Drug developers and clinicians are starting to rely more heavily on therapies that directly target the microbiota and on the ecology of the microbiota to understand the outcomes of these treatments. The effects of those microbiota-targeted therapies that alter community composition range in scale from eliminating individual strains of a single species (for example, with antibacterial conjugate vaccines) to replacing the entire community with a new intact microbiota (for example, by fecal transplantation). Secondary infections linked to antibiotic use provide a cautionary tale of the unintended consequences of perturbing a microbial species network and highlight the need for new narrow-spectrum antibiotics with rapid companion diagnostics. Insights into microbial ecology will also benefit the development of probiotics, whose therapeutic prospects will depend on rigorous clinical testing. Future probiotics may take the form of a consortium of long term community residents: "a fecal transplant in a capsule." The efficacy of microbiota-targeted therapies will need to be assessed using new diagnostic tools that measure community function rather than composition, including the temporal response of a microbial community to a defined perturbation such as an antibiotic or probiotic. PMID- 22674556 TI - Therapeutic modulation of microbiota-host metabolic interactions. AB - The complex metabolic relationships between the host and its microbiota change throughout life and vary extensively between individuals, affecting disease risk factors and therapeutic responses through drug metabolism. Elucidating the biochemical mechanisms underlying this human supraorganism symbiosis is yielding new therapeutic insights to improve human health, treat disease, and potentially modify human disease risk factors. Therapeutic options include targeting drugs to microbial genes or co-regulated host pathways and modifying the gut microbiota through diet, probiotic and prebiotic interventions, bariatric surgery, fecal transplants, or ecological engineering. The age-associated co-development of the host and its microbiota provides a series of windows for therapeutic intervention from early life through old age. PMID- 22674557 TI - Microbiota, disease, and back to health: a metastable journey. AB - Alterations in the composition of the commensal microbiota have been observed in many complex diseases. Understanding the basis for these changes, how they relate to disease risk or activity, and the mechanisms by which the symbiotic state of colonization resistance and host homeostasis is restored is critical for future therapies aimed at manipulating the microbiota. PMID- 22674560 TI - Progression and management of Wegener's granulomatosis in the head and neck. AB - OBJECTIVES/HYPOTHESIS: To describe the otolaryngologic presentation and natural history of granulomatosis with polyangiitis (GPA), previously known as Wegener's granulomatosis, and to compare otolaryngologic outcomes of patients with systemic GPA to those with a limited form of GPA confined to the head and neck. STUDY DESIGN: Retrospective chart review. METHODS: Review of GPA cases (identified by serology, biopsy, or clinical presentation) seen in the otolaryngology department of an academic medical center. RESULTS: A total of 24 patients were identified; each patient was followed for an average 6.8 years. Sinusitis and subglottic stenosis were the most commonly observed head and neck manifestations at diagnosis, seen in 64% and 36%, respectively. Over time, disease spread to additional sites in more than half the cohort (n = 14), but only two of 13 patients with disease initially limited to the head and neck developed pulmonary disease, and none developed renal disease. Cumulatively, otitis media was more likely to be observed in patients with systemic disease (P = .04). Patients with localized (n = 12) and systemic (n = 12) GPA did not have significantly different rates of surgical interventions (0.55 vs. 0.72 surgical interventions/patient year of follow-up, respectively, P = .19). CONCLUSIONS: GPA has a variety of head and neck manifestations, most commonly sinusitis, nasal disease, subglottic stenosis, and otitis media. GPA commonly progresses to involve additional sites, regardless of the extent of disease. These patients require frequent surgical intervention, and the clinician should remain vigilant for progression of disease. PMID- 22674561 TI - An eight-year study of online lecture use in a medical gross anatomy and embryology course. AB - Online lectures have been used in lieu of live lectures in our gross anatomy and embryology course for the past eight years. We examined patterns of online lecture use by our students and related that use to academic entry measures, gender and examination performance. Detailed access records identified by student were available from server logs. Total views per page of lecture material increased over the first six years, then decreased markedly between years seven and eight, possibly due to the recent availability of alternate forms of lecture audio. Lecture use peaked in midafternoon and again in the evening, although some use was seen at all hours. Usage was highest at midweek and lowest on Fridays as might be expected. Individual student's use varied widely from rates equivalent to less than one viewing/page to more than three viewings per page. Overall use by male students was greater than that of females and gender-specific differences in the daily pattern were seen. Lecture use was correlated to the Medical College Admission Test((r)) (MCAT((r))) Verbal Reasoning and Physical Sciences scores but not to composite MCAT scores or undergraduate grade point average. Overall use appeared to be driven by scheduled team-based learning (TBL) sessions and major examinations. Specific subsets of lecture material were most often viewed before related TBL sessions and again during review for examinations. A small but significant correlation between lecture use and examination and course performance was seen, specifically in the male student population. These findings, along with earlier observations, suggest that varied use of online lectures is attributable to multiple factors. PMID- 22674562 TI - C-C bond formation with carbon dioxide promoted by a silver catalyst. AB - A catalytic amount of silver benzoate with 7-methyl-1,5,7-triazabicyclo[4.4.0]dec 5-ene (MTBD) was an effective catalytic system for the reaction of carbon dioxide with various ketones containing an alkyne group at an appropriate position. These reactions afforded the corresponding gamma-lactone derivatives in good to high yields under mild conditions. PMID- 22674563 TI - Peptide targeted lipid nanoparticles for anticancer drug delivery. AB - Encapsulating anticancer drugs in nanoparticles has proven to be an effective mechanism to alter the pharmacokinetic and pharmacodynamic profiles of the drugs, leading to clinically useful cancer therapeutics like Doxil and DaunoXome. Underdeveloped tumor vasculature and lymphatics allow these first-generation nanoparticles to passively accumulate within the tumor, but work to create the next-generation nanoparticles that actively participate in the tumor targeting process is underway. Lipid nanoparticles functionalized with targeting peptides are among the most often studied. The goal of this article is to review the recently published literature of targeted nanoparticles to highlight successful designs that improved in vivo tumor therapy, and to discuss the current challenges of designing these nanoparticles for effective in vivo performance. PMID- 22674564 TI - Time course, clinical pathways, and long-term hazards risk trends of disease progression in patients with classic mycosis fungoides: a multicenter, retrospective follow-up study from the Italian Group of Cutaneous Lymphomas. AB - BACKGROUND: Mycosis fungoides (MF) is an indolent primary cutaneous T-cell lymphoma. To the authors' knowledge, no data currently are available regarding the evolution over time of the risk of developing specific pathways of disease progression. METHODS: This retrospective study analyzed 1422 patients with MF who were diagnosed and followed from 1975 through 2010 in 27 Italian Study Group for Cutaneous Lymphoma centers. The primary objectives were to ascertain the time course, pathways, and hazards risk trends of cutaneous/extracutaneous disease progression; to evaluate whether different tumor-lymph node-metastasis-blood (TNMB) stages have different pathways of disease progression; and to analyze differences between tumor-stage and erythrodermic MF with regard to clinical onset, disease evolution, and prognosis. The secondary objective was to provide a further validation for the revised International Society for Cutaneous Lymphomas and the Cutaneous Lymphoma Task Force of the European Organization of Research and Treatment of Cancer (ISCL/EORTC) classification. RESULTS: The median follow up was 14.5 years; stage progression occurred in 29.7% of patients and blood involvement was the most frequent extracutaneous site of disease progression. Patients with stage IA to stage IB disease demonstrated a steady low annual incidence of disease progression to tumor-stage (1%-2%); patients with stage IIA disease had a higher risk within the first years (up to 9.4%). Erythroderma evolved with a significantly higher frequency from patches/plaques (13.9%/28.2%) than tumors (P = .028 and P = .013, respectively). Hazards rates of extracutaneous involvement were low (< 1%). The T-score was found to be associated with extracutaneous involvement site, tumor-stage disease with lymph node/visceral lesions, and erythroderma with blood involvement. TNMB classification and stage progression resulted as independent prognostic variables being detected on multivariate analysis; the type of extracutaneous involvement was found to affect survival . CONCLUSIONS: The data from the current study support the need for a stage-tailored follow-up, suggest that the classification of tumor-stage disease at a stage below erythroderma could be modified, and offer a further validation for the revised TNMB classification. PMID- 22674565 TI - A pilot study examining the effects of Kouk Sun Do on university students with anxiety symptoms. AB - The effects of Kouk Sun Do (KSD), a mind-body exercise on mental health in university students, were investigated in this pilot study. University students (N = 30) with self-reported anxiety symptoms were randomly assigned to either the treatment group or the waiting list control group. Eighteen participants (N = 18; seven in the treatment group and 11 in the waiting list control group) completed a pre-test and a post-test, and 12 participants dropped out before or during the intervention. Ten 70-min KSD exercise sessions were conducted three times per week over a 4-week period. Trait anxiety, depressive symptoms and general self efficacy in coping with stress were measured with the pre-test and the post-test. Qualitative data were collected using open-ended questions regarding benefits of KSD at the last session. A two (group) by two (time) repeated-measure analysis of variance was used to analyse the data. Trait anxiety and depressive symptoms decreased whereas general self-efficacy increased over a 4-week period. The treatment group had significantly reduced trait anxiety and depressive symptoms compared with the control group across time. Qualitative data provided support that the self-induced relaxation effects of KSD may lead to reduced anxiety. PMID- 22674566 TI - pH-controlled delivery of doxorubicin to cancer cells, based on small mesoporous carbon nanospheres. AB - Mesoporous carbon nanospheres (MCNs) with small diameters of ~90 nm are developed as an efficient transmembrane delivery vehicle of an anticancer drug, doxorubicin (DOX). MCNs exhibit a high loading capacity toward DOX due to hydrophobic interactions and the supramolecular pi stacking between DOX and the carbonaceous structures, on which the pH-dependent drug release are successfully achieved. Specifically, DOX can be loaded onto MCNs in basic solution and in a physiological pH range, while release occurs in acidic solution in its ionized state. By effective passive and active targeting, MCNs can be readily internalized into HeLa cells, where the carried DOX can be efficiently released in the acidic microenvironment of the tumors for further therapy. The endocytosis and cytotoxicity of DOX@MCNs toward HeLa cells are investigated by confocal microscopy and MTT assay. This smart pH-dependent drug loading and release property of DOX@MCNs makes it possible to reduce the cytotoxicity to normal tissues during circulation in the body since the normal physiological pH is ~7.4. PMID- 22674567 TI - Motor cortex stimulation in refractory pelvic and perineal pain: report of two successful cases. AB - AIMS: In some patients, with refractory chronic pelvic and perineal pain, pain and quality of life are barely alleviated despite optimal medical treatment, infiltrations and surgical release of the pudendal nerve. The management of these patients is complex, especially after failure of neuromodulation techniques (spinal cord stimulation. S3 nerve root stimulation and direct stimulation of the pudendal nerve). We report the first two cases illustrating the value of motor cortex stimulation (MCS), in this new indication. METHODS: The history, decision making process, intraoperative findings and results of this technique are presented. The perineal cortical area was identified by intraoperative motor evoked potentials in the external anal sphincter, confirming its location in the primary motor cortex between the inferior and superior limb positions. As predictive value of repetitive transcranial magnetic stimulation (rTMS) in the identification of responders to MCS for pain is now established, we performed pre operative rTMS sessions for both patients. RESULTS: The first patient was a 74 years-old woman who reported an 11-year history of left lateral perineal pain. The second patient was a 45-year-old woman who reported a 4-year history of perineal pain following hysterectomy with ovariectomy. After respectively 40 months and 19 months of follow up, both patients reported an improvement of pain ranging from 40 to 50%. Time to onset of pain on sitting was markedly improved from a few minutes to 90 minutes, and largely contributing to improvement of activities of daily living and of quality of life. CONCLUSION: These two first cases suggest that motor cortex stimulation constitutes a new treatment for refractory pelvic and perineal pain, and should be considered after failure of conventional neuromodulation techniques, especially spinal cord stimulation. PMID- 22674568 TI - Structural and functional abnormalities in migraine patients without aura. AB - Migraine is a primary headache disorder characterized by recurrent attacks of throbbing pain associated with neurological, gastrointestinal and autonomic symptoms. Previous studies have detected structural deficits and functional impairments in migraine patients. However, researchers have failed to investigate the functional connectivity alterations of regions with structural deficits during the resting state. Twenty-one migraine patients without aura and 21 age- and gender-matched healthy controls participated in our study. Voxel-based morphometric (VBM) analysis and functional connectivity were employed to investigate the abnormal structural and resting-state properties, respectively, in migraine patients without aura. Relative to healthy comparison subjects, migraine patients showed significantly decreased gray matter volume in five brain regions: the left medial prefrontal cortex (MPFC), dorsal anterior cingulate cortex (dACC), right occipital lobe, cerebellum and brainstem. The gray matter volume of the dACC was correlated with the duration of disease in migraine patients, and thus we chose this region as the seeding area for resting-state analysis. We found that migraine patients showed increased functional connectivity between several regions and the left dACC, i.e. the bilateral middle temporal lobe, orbitofrontal cortex (OFC) and left dorsolateral prefrontal cortex (DLPFC). Furthermore, the functional connectivity between the dACC and two regions (i.e. DLPFC and OFC) was correlated with the duration of disease in migraine patients. We suggest that frequent nociceptive input has modified the structural and functional patterns of the frontal cortex, and these changes may explain the functional impairments in migraine patients. PMID- 22674569 TI - Nitroolefins as a nucleophilic component for highly stereoselective aza Henry reaction under the catalysis of chiral ammonium betaines. PMID- 22674571 TI - Stable sensitization of ZnO by improved anchoring of indoline dyes. PMID- 22674570 TI - Elevated pretreatment serum levels of interferon-inducible protein-10 (CXCL10) predict disease relapse and prognosis in diffuse large B-cell lymphoma patients. AB - Although standard clinical prognostic factors predict outcome in diffuse large B cell lymphoma (DLBCL), predicting the outcome of patients might be further refined using biological factors. We tested whether serum cytokines could provide prognostic information in DLBCL patients. Thirty cytokines were measured in pretreatment samples from newly diagnosed DLBCL patients using a multiplex ELISA. Sixty-nine patients treated with R-CHOP plus epratuzumab were used in an initial cohort and 185 patients treated with standard R-CHOP served as a subsequent validation cohort. In the initial cohort, elevated serum interleukin-10 [IL-10; hazard ratio (HR) = 6.6, P = 0.022], granulocyte macrophage colony-stimulating factor (HR = 10.8, P= 0.027) and IP-10 (interferon-inducible protein-10, CXCL10; HR = 3.32, P = 0.015) were associated with event-free survival (EFS). An identical analysis of the subsequent validation cohort confirmed that elevated serum levels of IP-10 were strongly associated with a poor EFS (HR = 2.42, P = 0.0007); and also identified interleukin-8 (IL-8; HR = 3.40, P = 0.00002) and interleukin-2 receptor (IL-2R, CD25; HR = 2.59, P = 0.0012) as significantly associated with prognosis. The prognostic significance of elevated IP-10 remained significant after adjustment for the International Prognostic Index (EFS - HR 1.99, P = 0.009, overall survival-HR 1.93, P = 0.021). Elevated pretreatment serum IP-10 levels are therefore associated with an increased likelihood of disease relapse and an inferior survival in patients with DLBCL. PMID- 22674572 TI - Fluorodeoxyglucose positron emission tomography in semantic dementia after 6 months of memantine: an open-label pilot study. AB - OBJECTIVES: To follow up on the increases we reported in normalized metabolic activity in salience network hubs from a 2-month open-label study of memantine in frontotemporal dementia (FTD). METHODS: We repeated fluorodeoxyglucose positron emission tomography (FDG-PET) after 6 months of drug use and subjected the data to Statistical Parametrical Mapping (SPM) analysis to reveal clusters of significant change from baseline. We also sought correlations between changes in behavioral disturbances on the Frontal Behavioral Inventory (FBI) and the PET signal. RESULTS: Recruitment of one progressive nonfluent aphasia and one behavioral variant FTD precluded statistical analysis for any FTD subtype other than semantic dementia (SD). The baseline-to-6-month interval showed increased normalized metabolic activity in the left orbitofrontal cortex (p < 0.002) for five participants with SD. The 2-6-month interval revealed a late increase in normalized metabolic activity in the left insula (p < 0.013), right insula (p < 0.009), and left anterior cingulate (p < 0.005). The right anterior cingulate showed both an initial increase and a delayed further increase (2-6 months, p < 0.016). FBI scores worsened by 43.3%. One participant with SD opted not to continue memantine beyond 2 months yet showed similar FDG-PET increases. CONCLUSIONS: Increases in normalized cortical metabolic activity in salience network hubs were sustained in SD over a 6-month period. Because one participant without medication also showed these changes, further investigation is recommended through a double-blind, placebo-controlled study with FDG-PET as an outcome measure. PMID- 22674573 TI - A potential neuroprotective role of apolipoprotein E-containing lipoproteins through low density lipoprotein receptor-related protein 1 in normal tension glaucoma. AB - Glaucoma is an optic neuropathy and the second major cause of blindness worldwide next to cataracts. The protection from retinal ganglion cell (RGC) loss, one of the main characteristics of glaucoma, would be a straightforward treatment for this disorder. However, the clinical application of neuroprotection has not, so far, been successful. Here, we report that apolipoprotein E-containing lipoproteins (E-LPs) protect primary cultured RGCs from Ca(2+)-dependent, and mitochondrion-mediated, apoptosis induced by glutamate. Binding of E-LPs to the low density lipoprotein receptor-related protein 1 recruited the N-methyl-d aspartate receptor, blocked intracellular Ca(2+) elevation, and inactivated glycogen synthase kinase 3beta, thereby inhibiting apoptosis. When compared with contralateral eyes treated with phosphate-buffered saline, intravitreal administration of E-LPs protected against RGC loss in glutamate aspartate transporter-deficient mice, a model of normal tension glaucoma that causes glaucomatous optic neuropathy without elevation of intraocular pressure. Although the presence of alpha2-macroglobulin, another ligand of the low density lipoprotein receptor-related protein 1, interfered with the neuroprotective effect of E-LPs against glutamate-induced neurotoxicity, the addition of E-LPs overcame the inhibitory effect of alpha2-macroglobulin. These findings may provide a potential therapeutic strategy for normal tension glaucoma by an LRP1 mediated pathway. PMID- 22674574 TI - Transforming growth factor-beta/SMAD Target gene SKIL is negatively regulated by the transcriptional cofactor complex SNON-SMAD4. AB - The human SKI-like (SKIL) gene encodes the SMAD transcriptional corepressor SNON that antagonizes TGF-beta signaling. SNON protein levels are tightly regulated by the TGF-beta pathway: whereas a short stimulation with TGF-beta decreases SNON levels by its degradation via the proteasome, longer TGF-beta treatment increases SNON levels by inducing SKIL gene expression. Here, we investigated the molecular mechanisms involved in the self-regulation of SKIL gene expression by SNON. Bioinformatics analysis showed that the human SKIL gene proximal promoter contains a TGF-beta response element (TRE) bearing four groups of SMAD-binding elements that are also conserved in mouse. Two regions of 408 and 648 bp of the human SKIL gene (~2.4 kb upstream of the ATG initiation codon) containing the core promoter, transcription start site, and the TRE were cloned for functional analysis. Binding of SMAD and SNON proteins to the TRE region of the SKIL gene promoter after TGF-beta treatment was demonstrated by ChIP and sequential ChIP assays. Interestingly, the SNON-SMAD4 complex negatively regulated basal SKIL gene expression through binding the promoter and recruiting histone deacetylases. In response to TGF-beta signal, SNON is removed from the SKIL gene promoter, and then the activated SMAD complexes bind the promoter to induce SKIL gene expression. Subsequently, the up-regulated SNON protein in complex with SMAD4 represses its own expression as part of the negative feedback loop regulating the TGF-beta pathway. Accordingly, when the SNON-SMAD4 complex is absent as in some cancer cells lacking SMAD4 the regulation of some TGF-beta target genes is modified. PMID- 22674575 TI - Cdc37/Hsp90 protein complex disruption triggers an autophagic clearance cascade for TDP-43 protein. AB - The RNA-binding protein, trans-active response DNA-binding protein 43 (TDP-43), is normally found in the nucleus, but in amyotrophic lateral sclerosis, frontal temporal dementia, and some cases of Alzheimer disease it is cleaved and mislocalized to the cytosol, leading to accumulation. The mechanisms contributing to this are largely unknown. Here, we show that part of the normal clearance cascade for TDP-43 involves the Cdc37/Hsp90 complex. An Hsp90 inhibitor that disrupts the Cdc37/Hsp90 complex reduced TDP-43 levels to a greater extent than a standard Hsp90 ATPase inhibitor. When Cdc37 was depleted, TDP-43 underwent proteolytic clearance that was dependent on nuclear retrotranslocation and autophagic uptake. Accumulation of the microtubule-associated protein tau prevented the clearance of cleaved TDP-43, but not its production. This caused cleaved TDP-43 to accumulate, a feature observed in the brain of persons with Alzheimer disease. Clearance of cleaved TDP-43 was also prevented by knockdown of the autophagic inducer beclin1. Thus, in cells where TDP-43 clearance is normally needed, a system that employs manipulation of the Hsp90 complex and autophagy exists. But when tau accumulation is occurring, cleaved TDP-43 can no longer be cleared, perhaps explaining the emergence of these co-pathologies. PMID- 22674576 TI - Accumulation of newly synthesized F1 in vivo in arabidopsis mitochondria provides evidence for modular assembly of the plant F1Fo ATP synthase. AB - F(1) subcomplex in mitochondrial samples is often considered to be a breakage product of the F(1)F(O) ATP synthase during sample handling and electrophoresis. We have used a progressive (15)N incorporation strategy to investigate the plant F(1)F(O) ATP synthase assembly model and the apparently free F(1) in plant mitochondria which is found in both the inner membrane and matrix. We show that subunits within F(1) in the inner membrane and matrix had a relatively higher (15)N incorporation rate than corresponding subunits in intact membrane F(1)F(O). This demonstrates that free F(1) was a newer pool with a faster turnover rate consistent with it being an assembly intermediate in vivo. Import of [(35)S]Met labeled F(1) subunit precursors into Arabidopsis mitochondria showed the rapid accumulation of F(1) assembly intermediates. The different (15)N incorporation rate in matrix F(1), inner membrane F(1) and intact F(1)F(O) demonstrates these three represent different protein populations and are likely step by step intermediates during the assembly process of plant mitochondrial ATP synthase. The potential biological implications of in vivo accumulation of enzymatically active F(1) in mitochondria are discussed. PMID- 22674577 TI - Structural mechanism of ATP-induced polymerization of the partition factor ParF: implications for DNA segregation. AB - Segregation of the bacterial multidrug resistance plasmid TP228 requires the centromere-binding protein ParG, the parH centromere, and the Walker box ATPase ParF. The cycling of ParF between ADP- and ATP-bound states drives TP228 partition; ATP binding stimulates ParF polymerization, which is essential for segregation, whereas ADP binding antagonizes polymerization and inhibits DNA partition. The molecular mechanism involved in this adenine nucleotide switch is unclear. Moreover, it is unknown how any Walker box protein polymerizes in an ATP dependent manner. Here, we describe multiple ParF structures in ADP- and phosphomethylphosphonic acid adenylate ester (AMPPCP)-bound states. ParF-ADP is monomeric but dimerizes when complexed with AMPPCP. Strikingly, in ParF-AMPPCP structures, the dimers interact to create dimer-of-dimer "units" that generate a specific linear filament. Mutation of interface residues prevents both polymerization and DNA segregation in vivo. Thus, these data provide insight into a unique mechanism by which a Walker box protein forms polymers that involves the generation of ATP-induced dimer-of-dimer building blocks. PMID- 22674578 TI - Structural insights into the catalytic active site and activity of human Nit2/omega-amidase: kinetic assay and molecular dynamics simulation. AB - Human nitrilase-like protein 2 (hNit2) is a putative tumor suppressor, recently identified as omega-amidase. hNit2/omega-amidase plays a crucial metabolic role by catalyzing the hydrolysis of alpha-ketoglutaramate (the alpha-keto analog of glutamine) and alpha-ketosuccinamate (the alpha-keto analog of asparagine), yielding alpha-ketoglutarate and oxaloacetate, respectively. Transamination between glutamine and alpha-keto-gamma-methiolbutyrate closes the methionine salvage pathway. Thus, hNit2/omega-amidase links sulfur metabolism to the tricarboxylic acid cycle. To elucidate the catalytic specificity of hNit2/omega amidase, we performed molecular dynamics simulations on the wild type enzyme and its mutants to investigate enzyme-substrate interactions. Binding free energies were computed to characterize factors contributing to the substrate specificity. The predictions resulting from these computations were verified by kinetic analyses and mutational studies. The activity of hNit2/omega-amidase was determined with alpha-ketoglutaramate and succinamate as substrates. We constructed three catalytic triad mutants (E43A, K112A, and C153A) and a mutant with a loop 116-128 deletion to validate the role of key residues and the 116-128 loop region in substrate binding and turnover. The molecular dynamics simulations successfully verified the experimental trends in the binding specificity of hNit2/omega-amidase toward various substrates. Our findings have revealed novel structural insights into the binding of substrates to hNit2/omega-amidase. A catalytic triad and the loop residues 116-128 of hNit2 play an essential role in supporting the stability of the enzyme-substrate complex, resulting in the generation of the catalytic products. These observations are predicted to be of benefit in the design of new inhibitors or activators for research involving cancer and hyperammonemic diseases. PMID- 22674580 TI - Generation of polyfluoroaryl-fused H-pyrazolo[5,1-a]isoquinolines through a reaction of N'-(2-alkynylbenzylidene)hydrazide with polyfluoroarene. AB - Polyfluoroarene reacts with N'-(2-alkynylbenzylidene)hydrazide catalyzed by silver triflate in the presence of cesium carbonate, leading to polyfluoroaryl fused H-pyrazolo[5,1-a]isoquinolines in good yields. PMID- 22674579 TI - Multiple post-translational modifications affect heterologous protein synthesis. AB - Post-translational modifications (PTMs) are required for proper folding of many proteins. The low capacity for PTMs hinders the production of heterologous proteins in the widely used prokaryotic systems of protein synthesis. Until now, a systematic and comprehensive study concerning the specific effects of individual PTMs on heterologous protein synthesis has not been presented. To address this issue, we expressed 1488 human proteins and their domains in a bacterial cell-free system, and we examined the correlation of the expression yields with the presence of multiple PTM sites bioinformatically predicted in these proteins. This approach revealed a number of previously unknown statistically significant correlations. Prediction of some PTMs, such as myristoylation, glycosylation, palmitoylation, and disulfide bond formation, was found to significantly worsen protein amenability to soluble expression. The presence of other PTMs, such as aspartyl hydroxylation, C-terminal amidation, and Tyr sulfation, did not correlate with the yield of heterologous protein expression. Surprisingly, the predicted presence of several PTMs, such as phosphorylation, ubiquitination, SUMOylation, and prenylation, was associated with the increased production of properly folded soluble proteins. The plausible rationales for the existence of the observed correlations are presented. Our findings suggest that identification of potential PTMs in polypeptide sequences can be of practical use for predicting expression success and optimizing heterologous protein synthesis. In sum, this study provides the most compelling evidence so far for the role of multiple PTMs in the stability and solubility of heterologously expressed recombinant proteins. PMID- 22674581 TI - Long-term outcomes in patients with locally advanced rectal cancer treated with preoperative chemoradiation followed by curative surgical resection. AB - OBJECTIVE: To determine the oncologic outcomes and clinical factors affecting survival in patients with locally advanced rectal cancer who underwent preoperative chemoradiotherapy (CRT) followed by curative surgical resection. METHODS: We retrospectively analyzed outcomes in 581 patients who underwent preoperative CRT for advanced rectal cancer (T3/4 or node positive) followed by curative resection. All patients received preoperative radiation to the entire pelvis, at a total dose of 45-50.4 Gy in 20-25 fractions for 4-5 weeks, and 569 (97.9%) patients received concurrent chemotherapy with a 5-FU based agent. All patients underwent a curative proctectomy, including total mesorectal excision, a median 6 weeks later, and 432 (74.4%) patients underwent sphincter-saving surgery. Oncologic outcomes, including survival and recurrence, were evaluated according to pathologic parameters, and factors affecting survival were investigated. RESULTS: The 5-year disease-free and overall survival rates were 72.4% and 77.8%, respectively. Eighty-nine patients (15.3%) had a pathologic complete response. Multivariate analysis showed that ypN category independently affected 5-year overall survival rates (ypN0 88.0%; ypN1 55.1%; ypN2 47.1%; P < 0.001). Factors independently affecting 5-year disease-free survival (DFS) rates included ypN category (ypN0 84.5%; ypN1 44.2%; ypN2 34.9%; P < 0.001), tumor regression grade (TRG1 52.9%; TRG2 72.0%; TRG3 86.7%; TRG4 86.8%; P = 0.004) and surgical method (sphincter-saving 76.3%; sphincter sacrificing 61.7%; P = 0.005). CONCLUSION: Less advanced pathologic N-stage is a significantly favorable prognostic factor for disease-free and overall survival, with good response and sphincter saving surgery benefiting DFS. PMID- 22674582 TI - Current knowledge and systematic review of viruses associated with Crohn's disease. AB - The aetiology of Crohn's disease (CD) is currently unknown. A viral trigger was proposed more than 40 years ago and has been the focus of many investigations. We summarised the current literature surrounding the association between viruses and CD and conducted a systematic review of all studies investigating this association quantitatively. Studies were identified by searching for 13 specific virus names or the general term 'virus' and 'Crohn's disease' in search engines PubMed and OVID. A total of 1315 studies were identified, of which 78 studies had a laboratory result. Of the 78, 46 case-control studies met all the inclusion criteria for forest plot analysis. The most common viruses studied were EBV, CMV and measles virus (MV). Forest plot analysis for each virus was carried out (fitted using random effects) and identified evidence of an association between CD and CMV (risk ratio [RR] 1.602, 95% confidence interval [CI] 1.069 to 2.400) with some suggestion that EBV may also be associated with CD (RR 1.366, 95% CI 0.996 to 1.873). However, there was evidence of large heterogeneity in the results from the identified studies for EBV. There was little evidence of an association with CD for MV, human herpes virus 6, human herpes virus 8, human simplex virus, varicella-zoster virus, mumps virus, Rubella virus, rotavirus, norovirus and adenovirus. There is still some question around whether CD is associated with the presence of a currently known virus. PMID- 22674583 TI - Assessing biodiversity funding during the sixth extinction. AB - Funding for understanding biodiversity on this planet has had a checkered and unsatisfactory history. There have been some true successes in developing models for assessing biodiversity, but satisfactory governmental and international support has been piecemeal and unsatisfactory. A true solution to the biodiversity crisis will require greater attention from governmental and international funding agencies. PMID- 22674584 TI - Matrix molecule influence on chondrocyte phenotype and proteoglycan 4 expression by alginate-embedded zonal chondrocytes and mesenchymal stem cells. AB - Articular cartilage resists load and provides frictionless movement at joint surfaces. The tissue is organized into the superficial, middle, deep, and calcified zones throughout its depth, each which serve distinct functions. Proteoglycan 4 (PRG4), found in the superficial zone, is a critical component of the joint's lubricating mechanisms. Maintenance of both the chondrocyte and zonal chondrocyte phenotype remain challenges for in vitro culture and tissue engineering. Here we investigate the expression of PRG4 mRNA and protein by primary bovine superficial zone chondrocytes, middle/deep zone chondrocytes, and mesenchymal stem cells encapsulated in alginate hydrogels with hyaluronic acid (HA) and chondroitin sulfate (CS) additives. Chondrogenic phenotype and differentiation markers are evaluated by mRNA expression, histochemical, and immunohistochemical staining. Results show middle/deep cells express no measurable PRG4 mRNA by day 7. In contrast, superficial zone cells express elevated PRG4 mRNA throughout culture time. This expression can be significantly enhanced up to 15-fold by addition of both HA and CS to scaffolds. Conversely, PRG4 mRNA expression is downregulated (up to 5-fold) by CS and HA in differentiating MSCs, possibly due to build up of entrapped protein. HA and CS demonstrate favorable effects on chondrogenesis by upregulating transcription factor Sox9 mRNA (up to 4.6-fold) and downregulating type I collagen mRNA (up to 18-fold). Results highlight the important relationship between matrix components and expression of critical lubricating proteins in an engineered cartilage scaffold. PMID- 22674585 TI - Microglia and neurodegeneration: the role of systemic inflammation. AB - It is well accepted that CNS inflammation has a role in the progression of chronic neurodegenerative disease, although the mechanisms through which this occurs are still unclear. The inflammatory response during most chronic neurodegenerative disease is dominated by the microglia and mechanisms by which these cells contribute to neuronal damage and degeneration are the subject of intense study. More recently it has emerged that systemic inflammation has a significant role to play in the progression of these diseases. Well-described adaptive pathways exist to transduce systemic inflammatory signals to the brain, but activation of these pathways appears to be deleterious to the brain if the acute insult is sufficiently robust, as in severe sepsis, or sufficiently prolonged, as in repeated stimulation with robust doses of inflammogens such as lipopolysaccharide (LPS). Significantly, moderate doses of inflammogens produce new pathology in the brain and exacerbate or accelerate features of disease when superimposed upon existing pathology or in the context of genetic predisposition. It is now apparent in multiple chronic disease states, and in ageing, that microglia are primed by prior pathology, or by genetic predisposition, to respond more vigorously to subsequent inflammatory stimulation, thus transforming an adaptive CNS inflammatory response to systemic inflammation, into one that has deleterious consequences for the individual. In this review, the preclinical and clinical evidence supporting a significant role for systemic inflammation in chronic neurodegenerative diseases will be discussed. Mechanisms by which microglia might effect neuronal damage and dysfunction, as a consequence of systemic stimulation, will be highlighted. PMID- 22674586 TI - An exploratory trial of Cyclamen europaeum extract for acute rhinosinusitis. AB - OBJECTIVES/HYPOTHESIS: An exploratory US trial in patients with acute rhinosinusitis was conducted to evaluate the efficacy and safety of Cyclamen europeaum extract, a product marketed in Europe that causes reflex nasal discharge and subsequent decongestion. STUDY DESIGN: Prospective, randomized, placebo-controlled, double-blind, and parallel group. METHODS: Outpatients (n = 29) with cardinal symptoms of acute rhinosinusitis and both endoscopic and radiographic (computed tomography [CT] scan) evidence at 25 US centers were randomized to receive intranasal, lyophilized, reconstituted Cyclamen europeaum extract (Cyclamen) or placebo spray for 7 days. Primary outcomes were reduction in percent sinus opacification on CT scans and reduction in PM predose instantaneous total symptom scores measured on a six-point scale. Secondary outcomes included other measures of symptom score change and endoscopic signs of mucopurulence and inflammation. RESULTS: Cyclamen treatment significantly reduced sinus opacification compared with placebo treatment (P < .045). Although Cyclamen treatment reduced total symptom scores from baseline more than placebo treatment (-2.4 vs. -1.4), there were no significant treatment group differences (P = .312). Cyclamen treatment was well tolerated. CONCLUSIONS: Cyclamen treatment significantly reduced sinus opacification in patients with acute rhinosinusitis. Further exploration of Cyclamen treatment in larger patient populations is warranted. PMID- 22674587 TI - Are clergy serving yoked congregations more vulnerable to burnout? A study among clergy serving in The Presbyterian Church (U.S.A.). AB - Pressures generated by increasing secularization and decreasing vocations to ordained ministry are resulting across denominations in a growing number of clergy serving more than one congregation. This study assesses the hypothesis that clergy serving more than one congregation are more susceptible to burnout. Data were provided by a sample of 735 clergy serving in The Presbyterian Church (USA) who completed the Francis burnout inventory together with the abbreviated Eysenck personality questionnaire revised. Among these clergy, 82% served one congregation, 13% served two congregations, and 5% served three or more congregations. After controlling for individual differences in age and personality, the data demonstrated that clergy serving yoked congregations experienced no statistically significant differences in susceptibility to burnout, either in terms of levels of emotional exhaustion or in terms of levels of satisfaction in ministry, compared with colleagues serving just one congregation. PMID- 22674588 TI - An emerging infectious cause of renal impairment in the UK. AB - Hantaviruses are endemic in many central European countries, particularly the Balkans, infection causing non-specific 'flu-like symptoms and renal dysfunction which is self-limiting in the majority of cases. In this case, there was a diagnostic delay, resulting in numerous unnecessary investigations, prolonged hospital stay and almost an invasive renal biopsy. A travel history is therefore essential, to establish travel to an endemic region within the previous 2-6 weeks. With increasing travel and immigration, hantavirus is likely to be seen more frequently as an imported infection into the UK. However, further research is required to establish the potential for acquisition of infection here, as the animal host, the bank vole, is part of local wildlife. Therefore, the authors urge physicians to be alert to this possibility when faced with acute renal failure in association with an undiagnosed febrile illness, particularly when there is a history of an appropriate environmental or animal exposure. PMID- 22674590 TI - Diffuse large B cell lymphoma: cutaneous manifestation. PMID- 22674589 TI - Dyselectrolytemia in acute kidney injury causing tetany and quadriparesis. AB - A 40-year-old female, presented with prerenal acute kidney injury secondary to diarrhoea. With appropriate hydration, she went into diuretic phase and subsequently developed hypokalemic quadriparesis with hypocalcaemic tetany due to hypomagnesemia and subclinical vitamin D deficiency. The patient improved with oral potassium, magnesium, calcium and vitamin D supplementation. PMID- 22674591 TI - Differential diagnosis of soft scalp lumps. AB - A 56-year-old man presented with a painless cyst on the top of his head which has been increasing in size in the last 6 months. Due to his learning disability, he could not be dissuaded from his belief that the lump was a sign of brain prolapse which led to increasing agitation in the next 2 weeks. A provisional diagnosis of benign lipoma was made and prompt excision was performed in his best interests. The lesion was more cystic and fluctuant than that of a lipoma and hence it was sent for histological diagnosis. The report came back as a trichilemmal cyst with no signs of proliferation. Cosmetic outcome was reasonable at follow-up after 3 months. The patient was scheduled for regular review every 6 months. PMID- 22674592 TI - Dipylidium caninum infection. AB - Dipylidium caninum is a cestode that requires from the participation of an arthropod in its life cycle. This parasitosis occurs in dogs and cats, and occasionally in human beings. Human cases of D caninum infection have been reported in Europe, Philippines, China, Japan, Latin America and the United States; mostly children, one third of them being infants under 6 months old. The diagnosis of this disease is done by the parasitological study of the feces, observing the characteristics of the gravid proglottids. The treatment is performed by administering broad-spectrum anthelmintics. The authors report a case of a rare infection in a Mexican child. PMID- 22674593 TI - Fusobacterium necrophorum--beyond Lemierres syndrome. AB - Fusobacterium necrophorum is a non-sporulating anaerobic gram negative bacillus and has traditionally been associated with Lemierre's syndrome. The authors report a 34-year-old male who presented to the emergency department with a week's history of dull epigastirc pain. Significant medical history included chronic pancreatitis secondary to alcohol use. The patient had radiological evidence of acute on chronic pancreatitis with thrombosis of the portal vein and multiple intrahepatic abscesses. CT-guided drainage of left upper quadrant revealed fluid collection in the pancreatic bed. The fluid culture grew F necrophorum and the patient was treated with tigecycline for 4 weeks. The patient improved symptomatically and his follow-up computerised axial tomography scan 2 months later showed resolving liver abscess, cavernous transformation of the portal vein and stable findings of chronic pancreatitis. This could represent an infection of the peripancreatic tissue with F necrophorum further leading to pylephlebitis. PMID- 22674594 TI - Ovarian ectopic pregnancy. AB - The authors report the rare case of a 25-year-old female who suffered from an ovarian ectopic pregnancy. She presented at 10 weeks gestation with a 1-day history of vaginal bleeding and lower abdominal discomfort. beta-human chorionic gonadotropin concentration was 8538 IU/ml. Ultrasound showed a right adnexal mass 4.0 * 3.8 * 5.5 cm with a 16 mm cystic area suggesting right ovarian ectopic pregnancy. Diagnostic laparoscopy confirmed a ruptured right ovarian ectopic pregnancy with haemoperitoneum. This was excised laparoscopically. She made a good postoperative recovery and was discharged on the second postoperative day. Histology confirmed a ruptured ovarian ectopic pregnancy. Ovarian ectopic pregnancy is a rare condition. There are two features that make this an unusual case; the relatively late gestation at which she presented and her mild presenting features. Unlike tubal ectopic pregnancies, which usually present at earlier gestations, this patient presented relatively late. She also presented with mild symptoms and signs. PMID- 22674595 TI - Anti-GBM disease and renal vein thrombosis. AB - A 23-year-old female who presented with advanced renal failure was subsequently diagnosed with renal vein thrombosis and antiglomerular basement membrane (GBM) antibody disease. A previous case of renal vein thrombosis has been reported in association with anti-GBM disease, but to our knowledge, this is the first reported case in which the presentation of anti-GBM disease and renal vein thrombosis was concurrent. Further study is essential to understand if the association of anti-GBM disease and renal vein thrombosis as seen in our case was pure coincidence or is in fact occurs more frequently. It may be that the dual diagnosis is not made as establishing one sufficient diagnosis for renal failure may halt further investigations for additional diagnoses. PMID- 22674596 TI - Apathy syndrome treated successfully with modafinil. AB - The treatment of apathy is often complicated and difficult. The authors present a case of apathy syndrome that was treated successfully with modafinil. An 87-year old widowed Brazilian woman presented with loss of interest and pleasure in activities. Her level of apathy, as evaluated by the Brazilian care giver version of the apathy scale, was 25 (a score higher than 18 points is associated with an apathy syndrome). No diagnosis of depression or sleep disorder was noted. After 2 years with many different antidepressants, modafinil treatment was started at 100 mg/day. One month after the initiation of modafinil therapy, the patient reported feeling more motivation, and she also returned to her favorite physical activity, which was swimming (400 m/day). Apathy scale revealed an improvement (18 points). Actigraphic analysis was performed, and no sleep disturbances were noted before or after treatment. Modafinil may be a promising option in the treatment of apathy. PMID- 22674597 TI - 'Idiopathic' chronic bilateral subdural haematoma--a separate entity or a missed cause? AB - A 65-year-old female was admitted with an 8-week history of gradual onset headache. The headache was worse in the morning and on bending forwards. This was associated with 1 week history of vomiting and 1 day history of difficulty in walking. Medical history was unremarkable apart from treated hypothyroidism. There was no history of trauma. Observations and physical examination were entirely normal. Routine blood tests including the ESR and clotting profile were normal. Given the history had red flags for headache, a CT scan was ordered and this showed bilateral subdural haematomas. The patient was referred to the regional neurosurgical centre where the haematomas were evacuated with good recovery. A follow-up MRI brain and spine did not show any source of bleeding. PMID- 22674598 TI - The contribution of skin camouflage volunteers in the management of vitiligo. AB - A 52-year-old woman with recently diagnosed vitiligo presented at the Skin Camouflage Clinic of the British Red Cross. She found these hypo-pigmented patches very distressing and wanted to be able to cover them up. She was referred to the clinic by her general practitioner. This service of the British Red Cross is run by volunteers and helps the patient find suitable creams, foundations and powders that even out the skin tone and so disguise skin conditions. This patient was taught how to apply the cream and left the clinic with an appreciably improved mood. Observational studies have highlighted an improvement in quality of life after the introduction of skin camouflage for vitiligo. This is a free service in the Red Cross and is a necessary part of its management, equipping the patient with practical ways to cope with a condition that does not usually respond well to treatment. PMID- 22674599 TI - Paediatric intrasubstance posterior cruciate ligament rupture. AB - The authors present the case of a 4-year-old boy who sustained an intrasubstance posterior cruciate ligament (PCL) tear whist trampolining. He was managed non operatively with return to full function by 8 months. A high index of suspicion is required when assessing paediatric hyperflexion/extension injuries at the knee as ligamentous injury may occur without osteochondral fracture and may be missed on routine radiographs. Early MRI can identify such injuries in addition to osteochondral avulsions which are often amenable to acute internal fixation. In the case of paediatric intrasubstance PCL tears, it appears that non-operative management yields a good functional outcome in the short term in the skeletally immature. PMID- 22674600 TI - Symplastic leiomyoma of uterus--a clinico-pathological dilemma. AB - The diagnosis of uterine smooth muscle tumours is usually not difficult. Occasionally, benign tumours with an unusual histopathology may cause some dilemma for clinicians who had not experienced such report before. A 50-year-old female patient was admitted to our gynaecology clinics with lower abdominal heaviness and urinary symptoms and undergone total abdominal hysterectomy with bilateral salpingo-oophorectomy with a probable diagnosis of cervical fibroid. Histopathological examination showed lipoleiomyoma uterus with focal symplastic features. This case report describes the clinic-pathological dilemma in managing the patient with symplastic leiomyoma of the uterus. PMID- 22674601 TI - Spontaneous intramural oesophageal haematoma: an unusual cause of chest pain. AB - The following case describes a 29-year-old previously well gentleman who presented with an acute onset of chest pain, dysphagia, odynophagia and vomiting without haematemesis. An oesophageal lesion was visualised on CT angiography and further investigation via oesophogastroduodenoscopy (OGD) diagnosed a spontaneous intramural oesophageal haematoma as the cause of his symptomatology. Conservative medical management in the form of triple therapy and softened diet was well tolerated and a follow-up OGD at 6 weeks after discharge from hospital showed spontaneous resolution of the haematoma. PMID- 22674602 TI - Shortness of breath in a CF patient: not always the chest. AB - The authors report the case of an adult with cystic fibrosis (CF) presenting with an episode of acute shortness of breath during an inpatient stay for infective exacerbation of CF. The treatment of bronchodilators and steroids for presumed airways disease was not effective and on review of the chest x-ray, it showed some evidence of pulmonary oedema. An echo showed a dilated left ventricle and globally reduced function. Serology came back positive for enterovirus which was in keeping with a diagnosis of myocarditis. PMID- 22674603 TI - Late onset mesh infection following laparoscopic inguinal hernia repair. AB - In our series of 710 consecutive laparoscopic total-extra-peritoneal hernia repairs over a period of 10 years (2001-2010), the authors report a rare case of delayed mesh infection developing 7 years postoperatively. A 56-year-old patient presented with diarrhoea and fullness in right iliac fossa region. Radiological imaging confirmed a floating mesh in a fluid-containing cavity. Subsequent exploration revealed a large preperitoneal cavity containing 550 ml of pus with a floating mesh in it. The mesh was removed and the patient was discharged after making a good recovery. PMID- 22674604 TI - Acute pancreatitis and acute respiratory distress syndrome complicating dengue haemorrhagic fever. AB - Dengue infection is now known to present with wide spectrum of complications. Isolated cases of acute pancreatitis complicating dengue haemorrhagic fever have been reported in literature. Here the authors report a case of dengue haemorrhagic fever that develops acute pancreatitis and presented with acute onset of breathlessness, which then progressed to full-blown acute respiratory distress syndrome. To our knowledge, this is the first reported case of dengue haemorrhagic fever complicated with acute pancreatitis and acute respiratory distress syndrome. PMID- 22674605 TI - Colossal hydronephrosis caused by pelvi-ureteric junction obstruction. PMID- 22674606 TI - A rare case of a ball and socket ankle joint. PMID- 22674607 TI - Aneurysmal subarachnoid haemorrhage in Parry-Rhomberg syndrome. AB - Parry-Romberg syndrome (PRS) or progressive hemi facial atrophy syndrome is a rare condition of unknown aetiology that is characterised by progressive unilateral facial and cranial atrophic changes of skin, subcutaneous tissues and bone. The authors describe a 37-year-old female with a history of PRS, who presented with a subarachnoid haemorrhage secondary to rupture of a 9 mm fusiform aneurysm of the posterior cerebral artery. There was an associated external carotid arterio-venous fistula noted with this aneurysm. The aneurysm was treated by endovascular route and was successfully coiled. Follow-up angiogram revealed spontaneous resolution of the fistula with good occlusion of the aneurysm. The aetio-pathogenesis of this rare occurrence, literature review and its management is discussed. PMID- 22674608 TI - Adult-onset migraine-related ophthalmoplegia and omolateral fetal-type posterior cerebral artery. AB - A 33-year-old woman with a long history of typical migraine without aura developed a pupillary-involving right third nerve palsy, after a typical migraine attack. The right pupil was 5 mm and showed delayed direct and consensual photomotor responses; the left pupil was 3 mm and reactive. Pupillary reaction to convergence was slow on the right eye. Ptosis, impaired elevation of the eye and weakened adduction were noted in the right eye. CT scan of the brain showed no abnormalities, whereas a CT digital cerebral angiography revealed a fetal-type right posterior cerebral artery (PCA). MRI disclosed thickening and contrast enhancement of the cisternal portion of the right oculomotor nerve. A lumbar puncture, performed 5 days after the onset of ocular symptoms, yielded acellular cerebrospinal fluid (CSF) with normal protein and glucose levels. Ptosis and diplopia recovered within a week, whereas blurred vision, anisocoria and accommodation deficit subsided after 10 weeks. PMID- 22674609 TI - Do images influence assessment in anatomy? Exploring the effect of images on item difficulty and item discrimination. AB - Anatomists often use images in assessments and examinations. This study aims to investigate the influence of different types of images on item difficulty and item discrimination in written assessments. A total of 210 of 460 students volunteered for an extra assessment in a gross anatomy course. This assessment contained 39 test items grouped in seven themes. The answer format alternated per theme and was either a labeled image or an answer list, resulting in two versions containing both images and answer lists. Subjects were randomly assigned to one version. Answer formats were compared through item scores. Both examinations had similar overall difficulty and reliability. Two cross-sectional images resulted in greater item difficulty and item discrimination, compared to an answer list. A schematic image of fetal circulation led to decreased item difficulty and item discrimination. Three images showed variable effects. These results show that effects on assessment scores are dependent on the type of image used. Results from the two cross-sectional images suggest an extra ability is being tested. Data from a scheme of fetal circulation suggest a cueing effect. Variable effects from other images indicate that a context-dependent interaction takes place with the content of questions. The conclusion is that item difficulty and item discrimination can be affected when images are used instead of answer lists; thus, the use of images as a response format has potential implications for the validity of test items. PMID- 22674611 TI - Helping depressed clients reconnect to positive emotion experience: current insights and future directions. AB - A deficit in the ability to experience pleasure (anhedonia) is one of the core symptoms of depression. However, therapy to date has predominantly focused on understanding elevations in negative emotion experience in depression and relatively neglected ways to reconnect individuals to positive experience. This article reviews current insights into blunted positivity in depression, evaluating evidence that depression leads to disturbances in anticipation (positive emotion experience when approaching a goal or a rewarding stimulus) and consummation (positive emotion experience when attaining a goal or rewarding stimulus), as well as impaired positive emotion recognition. The case is made that existing treatments are only partially effective and that therapy outcomes are likely to be improved by focusing on augmenting positivity, capitalizing on emerging insights from positive affective neuroscience. Existing and emerging therapeutic techniques that may aid the promotion of positivity are critiqued, and some suggestions for future research and clinical practice are outlined. PMID- 22674610 TI - Activation of Smad-mediated TGF-beta signaling triggers epithelial-mesenchymal transitions in murine cloned corneal progenitor cells. AB - Epithelial-mesenchymal transition (EMT), via activation of Wnt signaling, is prevailing in embryogenesis, but postnatally it only occurs in pathological processes, such as in tissue fibrosis and tumor metastasis. Our prior studies led us to speculate that EMT might be involved in the loss of limbal epithelial stem cells in explant cultures. To examine this hypothesis, we successfully grew murine corneal/limbal epithelial progenitors by prolonging the culture time and by seeding at a low density in a serum-free medium. Single cell-derived clonal growth was accompanied by a gradient of Wnt signaling activity, from the center to the periphery, marked by a centrifugal loss of E-cadherin and beta-catenin from intercellular junctions, coupled with nuclear translocation of beta-catenin and LEF-1. Large-colony-forming efficiency at central location of colony was higher than peripheral location. Importantly, there was also progressive centrifugal differentiation, with positive K14 keratin expression and the loss of p63 and PCNA nuclear staining, and irreversible EMT, evidenced by cytoplasmic expression of alpha-SMA and nuclear localization of S100A4; and by nuclear translocation of Smad4. Furthermore, cytoplasmic expression of alpha-SMA was promoted by high-density cultures and their conditioned media, which contained cell density-dependent levels of TGF-beta1, TGF-beta2, GM-CSF, and IL-1alpha. Exogenous TGF-beta1 induced alpha-SMA positive cells in a low-density culture, while TGF-beta1 neutralizing antibody partially inhibited alpha-SMA expression in a high-density culture. Collectively, these results indicate that irreversible EMT emerges in the periphery of clonal expansion where differentiation and senescence of murine corneal/limbal epithelial progenitors occurs as a result of Smad-mediated TGF-beta-signaling. PMID- 22674612 TI - Gefitinib versus pemetrexed as second-line treatment in patients with nonsmall cell lung cancer previously treated with platinum-based chemotherapy (KCSG-LU08 01): an open-label, phase 3 trial. AB - BACKGROUND: Gefitinib was compared with pemetrexed as second-line therapy in a clinically selected population previously treated with platinum-based chemotherapy. METHODS: A phase 3 trial of gefitinib (250 mg/day) versus pemetrexed (500 mg/m(2) on day 1, every 3 weeks) was conducted in patients who had never smoked and who had advanced pulmonary adenocarcinoma treated with 1 previous platinum-based regimen. The primary endpoint was progression-free survival (PFS). RESULTS: A total of 135 patients were analyzed. The gefitinib group had significantly longer PFS compared with the pemetrexed group, with a median PFS time of 9.0 versus 3.0 months (P = .0006). The objective response rates were 58.8% and 22.4% for gefitinib and pemetrexed, respectively (P < .001). However, there was no statistically significant difference in overall survival between the 2 groups (22.2 vs 18.9 months; P = .37). The difference of PFS was increased in a subgroup analysis of 33 patients with activating epidermal growth factor receptor mutation (15.7 vs 2.9 months; hazard ratio, 0.3; 95% confidence interval, 0.13-0.72; P = .005), with numerical superiority of gefitinib in the 38 patients testing negative for epidermal growth factor receptor mutation (5.9 vs 2.7 months; P = .099). Both regimens were well tolerated. There were no significantly different changes in quality of life between the 2 groups, except that symptom scores for dyspnea and diarrhea favored the gefitinib and pemetrexed arms, respectively. CONCLUSIONS: Gefitinib showed superior efficacy to pemetrexed as second-line therapy in Korean never-smokers with pulmonary adenocarcinoma. PMID- 22674613 TI - Management of singlet and triplet excitons in a single emission layer: a simple approach for a high-efficiency fluorescence/phosphorescence hybrid white organic light-emitting device. AB - A high-efficiency single-emission-layer (EML) hybrid white organic light emitting device is fabricated based on an ideal sky-blue fluorophor, DADBT, using a novel doping concentration regulation strategy, which effectively separates and respectively utilizes the singlet and triplet excitons in the single-EML. The white device shows excellent electroluminescence performance with maximum total efficiencies of 26.6%, 53.5 cd A(-1) and 67.2 lm W(-1) . PMID- 22674614 TI - Directionality of dihydrogen bonds: the role of transition metal atoms. AB - A theoretical study on two series of electron-rich group 8 hydrides is carried out to evaluate involvement of the transition metal in dihydrogen bonding. To this end, the structural and electronic parameters are computed at the DFT/B3PW91 level for hydrogen-bonded adducts of [(PP(3))MH(2)] and [Cp*MH(dppe)] (M = Fe, Ru, Os; PP(3) = kappa(4)-P(CH(2)CH(2)PPh(2))(3), dppe = kappa(2) Ph(2)PCH(2)CH(2)PPh(2)) with CF(3)CH(2)OH (TFE) as proton donor. The results are compared with those of adduct [Cp(2)NbH(3)]?TFE featuring a "pure" dihydrogen bond, and classical hydrogen bonds in pyridine?TFE and Me(3)N?TFE. Deviation of the H???H-A fragment from linearity is shown to originate from the metal participation in dihydrogen bonding. The latter is confirmed by the electronic parameters obtained by NBO and AIM analysis. Considered together, orbital interaction energies and hydrogen bond ellipticity are salient indicators of this effect and allow the MH???HA interaction to be described as a bifurcate hydrogen bond. The impact of the M???HA interaction is shown to increase on descending the group, and this explains the experimental trends in mechanisms of proton-transfer reactions via MH???HA intermediates. Strengthening of the M???H interaction in the case of electron-rich 5d metal hydrides leads to direct proton transfer to the metal atom. PMID- 22674615 TI - Doxorubicin-conjugated mesoporous magnetic colloidal nanocrystal clusters stabilized by polysaccharide as a smart anticancer drug vehicle. AB - Fabrication of magnetic nanocarriers that demonstrate enhanced biocompatibility and excellent colloidal stability is critical for the application of magnetic motored drug delivery, and it remains a challenge. Herein, a novel approach to synthesize mesoporous magnetic colloidal nanocrystal clusters (MMCNCs) that are stabilized by agarose is described; these clusters demonstrate high magnetization, large surface area and pore volume, excellent colloidal stability, enhanced biocompatibility, and acid degradability. The hydroxyl groups of agarose, which cover the surface of the magnetic nanocrystals, are modified with vinyl groups, followed by click reaction with mercaptoacetyl hydrazine to form the terminal hydrazide (-CONHNH(2)). The anticancer agent doxorubicin (DOX) is then conjugated to MMCNCs through a hydrazone bond. The resulting hydrazone is acid cleavable, thereby providing a pH-sensitive drug release capability. This novel carrier provides an important step towards the construction of a new family of magnetic-motored drug-delivery systems. The experimental results show that the release rate of DOX from the DOX-conjugated MMCNCs (MMCNCs-DOX) is dramatically improved at low pH (tumor cell: pH 4-5 in the late stage of endolysosome and pH 5 6 from the early to late endosome), while almost no DOX is released at neutral pH (blood plasma). The cell cytotoxicity of the MMCNCs-DOX measured by MTT assay exhibits a comparable antitumor efficacy but lower cytotoxicity for normal cell lines, when measured against the free drug, thus achieving the aim of reducing side effects to normal tissues associated with controlled drug release. PMID- 22674616 TI - Hierarchical nitrogen-doped flowerlike ZnO nanostructure and its multifunctional environmental applications. AB - Hierarchical nitrogen-doped ZnO flowerlike nanostructures were synthesized on a large scale. These nanostructures were characterized by FESEM, HRTEM, XRD, FTIR, XPS, and TGA, and their suitability for multifunctional environmental applications was investigated. The experimental results demonstrated that the hierarchical N-doped ZnO flowerlike nanostructure enhances the photodegradation of methyl blue (MB) and acid orange 7 (AO7) by presenting a large specific surface area and high light utilization rate, inhibits the growth of bacteria without light irradiation, and increases the permeate flux when used in a membrane filtration system. These advantages of the hierarchical N-doped ZnO flowerlike nanostructure brings benefits to the environmental application fields. PMID- 22674618 TI - Low-coordinate germanium(II) centers within distorted axially chiral seven membered chelates: stereo- and enantioselective cycloadditions. PMID- 22674617 TI - Chronic renal failure in lithium-using geriatric patients: effects of lithium continuation versus discontinuation--a 60-month retrospective study. AB - OBJECTIVE: Lithium remains an important treatment in bipolar disorder. Although lithium is often discontinued because of signs of renal failure, it is unclear if this alters the course of renal function in the majority of patients. We hypothesize that in geriatric patients with chronic renal failure (CRF), who have a high burden of medical illness, lithium continuation does not significantly impact renal function (glomerular filtration rate (eGFR)). METHODS: We conducted a retrospective study of tertiary-care geriatric psychiatry outpatients with a history of lithium use and evidence of CRF (eGFR <= 60 ml/min/1.73 m2 on >= 2 occasions in >= 3 months). The 27 patients who met these criteria were divided into lithium 'continuers' (continued use >= 2 years following CRF) and 'discontinuers'. Mean eGFR and creatinine were followed at 21 and 60 months after developing CRF. RESULTS: Mean serum eGFR and creatinine were not significantly different between groups at any time during follow-up. When comparing renal function at 60 months to baseline, a trend towards increased creatinine was seen in continuers (p = 0.06) but not in discontinuers. Changes in eGFR in continuers and discontinuers after 60 months did not achieve statistical significance (p = 0.35 and 0.98). However, clinically important decreases in eGFR occurred in the majority of continuers but in none of the discontinuers. CONCLUSIONS: There was a trend towards declining renal function in lithium continuers at 60-month follow up. Future prospective longitudinal studies will be needed to confirm our findings. We suggest vigilance and close monitoring of renal function when continuing CRF patients on lithium for extended periods. PMID- 22674619 TI - Reflux esophagitis increased the risk of bladder pain syndrome/interstitial cystitis: a 3-year follow-up study. AB - AIMS: Reflux esophagitis (RE) is a common disease which has been recognized to be associated with several medical co-morbidities. However, the association between RE and bladder pain syndrome/interstitial cystitis (BPS/IC) is still unknown. The present study aimed to explore the association between these two diseases. METHODS: We identified 8,962 female patients who had received a diagnosis of RE as the study cohort. We randomly selected 44,810 subjects to be included as the comparison cohort. Each patient in this study was individually tracked for a 3 year period to identify those who subsequently received a diagnosis of BPS/IC. Cox proportional hazards regressions were carried out to estimate the 3-year risk of BPS/IC following a diagnosis of RE. RESULTS: The incidence of BPS/IC following a diagnosis of RE was 4.3% during the follow-up period for all subjects. The incidence rate of BPS/IC was 2.38 [95% confidence interval (CI): 2.21-2.57] per 100 person-years in patients with RE, and 1.24 (95% CI: 1.18-1.30) per 100 person years in controls. Cox proportional analysis indicated that the hazard ratio (HR) of BPS/IC for patients with RE was 2.00 (95% CI = 1.82-2.20, P < 0.001) that of controls. The adjusted HR of BPS/IC for patients with RE was 1.40 (95% CI = 1.27 1.55, P < 0.001) after taking age group, urbanization level, and medical comorbidity into consideration. CONCLUSION: We found that patients with RE were at a higher risk than with comparison patients for having been subsequently diagnosed with BPS/IC during longitudinal follow-up. PMID- 22674620 TI - Purinergic receptors in microglia: functional modal shifts of microglia mediated by P2 and P1 receptors. AB - Microglia are sensitive to environmental changes and are immediately transformed into several phenotypes. For such dynamic "modal shifts", purinergic receptors have central roles. When microglia sense ATP/ADP leaked from injured cells by P2Y(12) receptors, they are transformed into a moving phenotype, showing process extension and migration toward the injured sites. Microglia upregulate adenosine A(2A) receptors, by which they retract the processes showing an amoeboid-shaped, activated phenotype. Microglia also upregulate P2Y(6) receptors, and if they meet UDP leaked from dead cells, microglia start to engulf and eat the dead cells as a phagocytic phenotype. The P2Y(12) receptor-mediated responses are modulated by other P2 or P1 receptors. In contrast, the P2Y(6) receptor-mediated responses were not influenced by P2Y(12) receptors and vice versa. Microglia appear to use purinergic signals either cooperatively or distinctively to cause their modal shifts. PMID- 22674621 TI - Long-term follow-up of reduced-intensity allogeneic hematopoietic stem cell transplantation for refractory or relapsed follicular lymphoma. AB - Although allogeneic hematopoietic stem cell transplantation (HSCT) is considered the only curative treatment for refractory or relapsed follicular lymphoma (FL), transplant-related mortality (TRM) greatly interferes with the success. A variety of reduced-intensity conditionings (RICs) have been used to reduce TRM, but an optimal conditioning for FL has not been fully established. We retrospectively evaluated the outcome of allogeneic HSCT for FL with RIC consisting of fludarabine and melphalan. Nineteen adult patients with relapsed or refractory FL were conditioned with fludarabine (125 mg/m2) and melphalan (140 mg/m2), and received grafts from an HLA-identical sibling (n = 6) or an unrelated donor (n = 13). For the prophylaxis of graft-versus-host disease (GVHD), cyclosporine A or tacrolimus with short-term methotrexate was given. There were no early deaths before engraftment, and all patients achieved engraftment. Three patients died of extensive-type chronic GVHD (n = 2) or bacterial infection (n = 1) without disease progression. With a median follow-up period of 75.2 months (range: 33.3 111.9 months), 16 patients were alive without disease progression. Both the 5 year overall and progression-free survival rates were 84.2% (95% CI: 67.7-100%). These results strongly suggest that allogeneic HSCT with RIC using fludarabine and melphalan could be a promising treatment choice for refractory or relapsed FL. PMID- 22674622 TI - Intraoperative intradermal skin testing. PMID- 22674623 TI - Characterization of hepatic adenoma and focal nodular hyperplasia with gadoxetic acid. AB - PURPOSE: To characterize imaging features of histologically proven hepatic adenoma (HA) as well as histologically and/or radiologically proven focal nodular hyperplasia (FNH) using delayed hepatobiliary MR imaging with 0.05 mmol/kg gadoxetic acid. MATERIALS AND METHODS: Five patients with six HAs with histological correlation were retrospectively identified on liver MRI studies performed with gadoxetic acid, and T1-weighted imaging acquired during the delayed hepatobiliary phase. Additionally, 23 patients with 34 radiologically diagnosed FNH lesions (interpreted without consideration of delayed imaging) were identified, two of which also had histological confirmation. Signal intensity ratios relative to adjacent liver were measured on selected imaging sequences. RESULTS: All six hepatic adenomas (100%), which had histological confirmation, demonstrated hypointensity relative to adjacent liver on delayed imaging. Furthermore, all of the FNH (including 34 radiologically proven, 2 of which were also histologically proven) were either hyperintense (23/34, 68%) or isointense (11/34, 32%) relative to the adjacent liver on delayed imaging. None of the FNHs were hypointense relative to liver. CONCLUSION: Distinct imaging characteristics of HA versus FNH on delayed gadoxetic acid-enhanced MRI, with adenomas being hypointense and FNH being iso- or hyperintense on delayed imaging may improve specificity for characterization, and aid in the differentiation of these two lesions. PMID- 22674624 TI - Quantitative analysis of acetaminophen and its six metabolites in rat plasma using liquid chromatography/tandem mass spectrometry. AB - Acetaminophen (APAP) is a widely used analgesic and antipyretic drug. It is mainly metabolized by phase 1 and 2 reactions in the liver, and thus it could be involved in many drug-drug interactions. Therefore, the study of APAP metabolism is important in toxicological and pharmacokinetic studies. The objective of this study was to develop a rapid and sensitive method for the determination of APAP and its six metabolites in rat plasma for the pharmacokinetic studies. APAP and its metabolites were separated through a Capcell Pak MGII C(18) column and quantitated with a 16 min run in a triple-quadruple mass spectrometer. The mobile phases were composed of 0.1% formic acid in either 95% water or 95% acetonitrile and analysis was performed twice in positive and negative modes. Validations such as accuracy, precision, recovery, matrix effect and stability were found to be within acceptance criteria of validation guidelines, indicating that the assay was applicable to the determination of the plasma concentrations of drug and its six metabolites. In conclusion, we developed an LC-MS/MS method for the quantitative analysis of APAP and its six metabolites in rat plasma, and this method appears to be useful for pharmacokinetic/toxicokinetic studies of APAP and its metabolites in rats. PMID- 22674625 TI - Improved prediction of Alzheimer's disease with longitudinal white matter/gray matter contrast changes. AB - Brain morphometry measures derived from magnetic resonance imaging (MRI) are important biomarkers for Alzheimer's disease (AD). The objective of the present study was to test whether we could improve morphometry-based detection and prediction of disease state by use of white matter/gray matter (WM/GM) signal intensity contrast obtained from conventional MRI scans. We hypothesized that including WM/GM contrast change along with measures of atrophy in the entorhinal cortex and the hippocampi would yield better classification of AD patients, and more accurate prediction of early disease progression. T1 -weighted MRI scans from two sessions approximately 2 years apart from 78 participants with AD (Clinical Dementia Rating (CDR) = 0.5-2) and 71 age-matched controls were used to calculate annual change rates. Results showed that WM/GM contrast decay was larger in AD compared with controls in the medial temporal lobes. For the discrimination between AD and controls, entorhinal WM/GM contrast decay contributed significantly when included together with decrease in entorhinal cortical thickness and hippocampal volume, and increased the area under the curve to 0.79 compared with 0.75 when using the two morphometric variables only. Independent effects of WM/GM contrast decay and improved classification were also observed for the CDR-based subgroups, including participants converting from either a non-AD status to very mild AD, or from very mild to mild AD. Thus, WM/GM contrast decay increased diagnostic accuracy beyond what was obtained by well validated morphometric measures alone. The findings suggest that signal intensity properties constitute a sensitive biomarker for cerebral degeneration in AD. PMID- 22674626 TI - AMPK inhibitor compound C suppresses cell proliferation by induction of apoptosis and autophagy in human colorectal cancer cells. AB - BACKGROUND AND OBJECTIVES: AMP-activated protein kinase (AMPK) is a main regulator of energy metabolism through the inhibition of biosynthetic pathways and enhancement of ATP-generating pathways. However, targeting AMPK as anti-tumor therapy remains controversial. In this study, we examined the effect of compound C, a small molecule inhibitor of AMPK, on the proliferation of several human colorectal cancer cell lines with diverse characteristics. METHODS: Four human colorectal cancer cell lines (HCT116, DLD-1, SW480, and KM12C) were treated with compound C. Cell viability was determined by MTS assay. Cell cycle prolife was analyzed by flow cytometry. Acidic vesicular organelles were detected by acridine orange staining. Protein levels were measured by western blotting. RESULTS: Compound C inhibited the growth of four cell lines in a dose-dependent manner and caused G(2) /M arrest. Compound C increased sub-G(1) cell population and induced chromatin condensation and cleavage of PARP in HCT116 and KM12C cells, while it induced acidic vesicular formation and conversion of LC3-I to autophagosome associated LC3-II in DLD-1 and SW480 cells. Survivin, an anti-apoptotic protein, was down-regulated in all cell lines treated with compound C. CONCLUSIONS: Compound C induces apoptotic or autophagic death in colorectal cancer cells and the preferred death mode is cell type-dependent. PMID- 22674627 TI - Alcohol versus brush PRK: visual outcomes and adverse effects. AB - BACKGROUND AND OBJECTIVE: A smooth corneal surface prior to laser ablation is important in order to achieve a favorable refractive outcome. In this study, we compare PRK outcomes following two commonly used methods of epithelial debridement: Amoils epithelial scrubber (brush) versus 20% ethanol (alcohol). STUDY DESIGN/PATIENTS AND METHODS: We reviewed records of patients who underwent wavefront-optimized PRK for myopia or myopic astigmatism between January 2008 and June 2010. Two treatment groups (brush vs. alcohol) were compared in terms of uncorrected distance visual acuity (UDVA), manifest refraction spherical equivalent (MRSE), corrected distance visual acuity (CDVA), and complications at postoperative months 1, 3, 6, and 12. RESULTS: One thousand five hundred ninety three eyes of 804 patients underwent PRK during the study period: 828 brush treated eyes and 765 alcohol-treated eyes. At 6 months postoperatively UDVA was >=20/20 in 94.7% of brush-treated eyes versus 94.4% of alcohol-treated eyes (P = 0.907). At 1 month a higher percentage of brush-treated eyes maintained or gained one or more lines CDVA compared to alcohol-treated eyes (P = 0.007), but there were no other differences in UDVA, MRSE, or CDVA at any point postoperatively. At 1 month 75.4% of brush-treated eyes versus 70.4% of alcohol-treated eyes were free of complications (P = 0.032), and there were fewer brush-treated eyes with corneal haze (4.0% vs. 6.9%, P = 0.012) and dry eye (8.9% vs. 14.4%, P = 0.001). Although corneal haze was slightly more frequent in the alcohol group, most was trace and not significant. CONCLUSIONS: Although alcohol-assisted PRK had more minor complications in the early postoperative period, including corneal haze and dry eye, results for both groups beyond 1 month were comparable. PMID- 22674628 TI - Nanoparticle-induced exosomes target antigen-presenting cells to initiate Th1 type immune activation. AB - The mechanisms associated with the induction of systemic immune responses by nanoparticles are not fully understood, but their elucidation is critical to address safety issues associated with the broader medical application of nanotechnology. In this study, a key role of nanoparticle-induced exosomes (extracellularly secreted membrane vesicles) as signaling mediators in the induction of T helper cell type 1 (Th1) immune activation is demonstrated. In vivo exposure to magnetic iron oxide nanoparticles (MIONs) results in significant exosome generation in the alveolar region of Balb/c mice. These act as a source of nanoparticle-induced, membrane-bound antigen/signaling cargo, which transfer their components to antigen-presenting cells (APCs) in the reticuloendothelial system. Through exosome-initiated signals, immature dendritic cells (iDCs) undergo maturation and differentiation to the DC1 subtype, while macrophages go through classical activation and differentiation to the M1 subtype. Simultaneously, iDCs and macrophages release various Th1 cytokines (including interleukin-12 and tumor necrosis factor alpha) driving T-cell activation and differentiation. Activated APCs (especially DC1 and M1 subtypes) consequently prime T-cell differentiation towards a Th1 subtype, thereby resulting in an orchestrated Th1-type immune response. Th1-polarized immune activation is associated with delayed-type hypersensitivity, which might underlie the long-term inflammatory effects frequently associated with nanoparticle exposure. These studies suggest that nanoparticle-induced exosomes provoke the immune activation and inflammatory responses that can accompany nanoparticle exposure. PMID- 22674629 TI - Naringenin inhibits extracellular matrix production via extracellular signal regulated kinase pathways in nasal polyp-derived fibroblasts. AB - Naringenin, a natural predominant flavanone derived from plant food, has antifibrotic activity. The purposes of this study were to determine the effect of naringenin on myofibroblast differentiation and extracellular matrix (ECM) production in nasal polyp-derived fibroblasts (NPDFs) and to determine the molecular mechanism of the effect of naringenin on NPDFs. NPDFs were incubated and treated with transforming growth factor (TGF)-beta1. The expression of alpha smooth muscle actin (alpha-SMA), fibronectin, and collagen type I mRNA was determined by a reverse transcription-polymerase chain reaction, and the expression of those proteins was determined by immunofluorescence staining or Western blotting. Expression of several signaling molecules of the TGF-beta1 pathway was evaluated by Western blot analysis. Naringenin inhibits expression of an indicator of myofibroblast differentiation (alpha-SMA) and ECM production, including collagen type 1 and fibronectin. Naringenin only suppressed the expression of extracellular signal-regulated protein kinase (pERK)1/2 among evaluated signaling molecules. PD98059 (a specific inhibitor of ERK1/2 kinase) also suppressed the increased expression of fibronectin, collagen type I, and alpha-SMA in TGF-beta1-induced NPDFs. These results suggest the possibility that naringenin may play an inhibitory role in the production of the ECM in the development of nasal polyps. PMID- 22674630 TI - Two adaptive weighting methods to test for rare variant associations in family based designs. AB - Although next-generation DNA sequencing technologies have made rare variant association studies feasible and affordable, the development of powerful statistical methods for rare variant association studies is still under way. Most of the existing methods for rare variant association studies compare the number of rare mutations in a group of rare variants (in a gene or a pathway) between cases and controls. However, these methods assume that all causal variants are risk to diseases. Recently, several methods that are robust to the direction and magnitude of effects of causal variants have been proposed. However, they are applicable to unrelated individuals only, whereas family data have been shown to improve power to detect rare variants. In this article, we propose two adaptive weighting methods for rare variant association studies based on family data for quantitative traits. Using extensive simulation studies, we evaluate and compare our proposed methods with two methods based on the weights proposed by Madsen and Browning. Our results show that both proposed methods are robust to population stratification, robust to the direction and magnitude of the effects of causal variants, and more powerful than the methods using weights suggested by Madsen and Browning, especially when both risk and protective variants are present. PMID- 22674631 TI - An MO-based identification of charge-shift bonds. PMID- 22674632 TI - Effects of common agricultural tasks on measures of hearing loss. AB - BACKGROUND: Among agricultural populations, hearing loss caused by excessive noise exposure is common. However, examinations of associations between exposure to agricultural tasks and hearing loss are limited. METHODS: Audiometry and lifetime exposure to 11 agricultural tasks were analyzed among 1,568 participants. Gender stratified multivariable linear regression was used to estimate associations between exposure duration and three hearing loss metrics. RESULTS: Among men, significant associations were observed between hearing loss and hunting or target shooting, all-terrain vehicle (ATV) or motorcycle riding, chain saw use, electric or pneumatic tool use, living on a farm, and all agricultural tasks combined. When all significant exposure metrics were included in a single model, associations remained for hunting or target shooting, electric or pneumatic tool use and living on a farm. Significant associations were sparse among women, and in all cases paradoxical. CONCLUSIONS: Despite imprecise estimation of noise exposure, specific agricultural tasks were associated with hearing loss. PMID- 22674633 TI - Ethylene glycol: a powerful catalyst-free medium for C-C bond-forming reactions. PMID- 22674634 TI - Feasibility and effectiveness of a Chen-style Tai Chi programme for stress reduction in junior secondary school students. AB - Stress is common in junior secondary school students (JSSS). This study aimed to determine the feasibility and effectiveness of a Chen-style Tai Chi programme for stress reduction in JSSS. A non-equivalent pre-test/post-test control group design was adopted, and a convenience sample of 69 JSSS was recruited. The experimental group (n = 32) joined a Chen-style Tai Chi programme, which included 10 sessions of 80-minute Tai Chi training (one session per week). The control group (n = 37) proceeded with self-study. Participants' stress levels were assessed using the Perceived Stress Scale. Feasibility was determined as the percentage of participants completing and attending the programme. Effectiveness was measured as the significant difference in changes in stress levels before and after the intervention between the two groups. Results preliminarily supported that the programme was feasible for JSSS. Completion rate was 100%, and attendance rate was 90%. However, no significant difference was noted in changes in stress levels before and after the intervention between the two groups. The potential health benefits of Tai Chi could not be detected owing to the restrictions imposed by the research setting and study limitations. The present study represents initial efforts in this direction and serves as reference for future study. PMID- 22674635 TI - Safety, pharmacokinetics, and activity of EZN-2208, a novel conjugate of polyethylene glycol and SN38, in patients with advanced malignancies. AB - BACKGROUND: EZN-2208 is a water-soluble, polyethylene glycol drug conjugate of SN38, which is the active moiety of irinotecan. In this study, the authors evaluated the tolerability, pharmacokinetics (PK), and activity of EZN-2208 in adult patients with advanced solid tumors. METHODS: Patients in sequential cohorts (3 + 3 design) received intravenous EZN-2208 at doses between 1.25 mg/m(2) and 25 mg/m(2) once every 21 days. RESULTS: Thirty-nine patients received EZN-2208. The median number of prior therapies was 2 (range, 0-10 prior therapies). Seventeen patients received prior irinotecan. Two maximum tolerated doses (MTDs) were defined: EZN-2208 with (16.5 mg/m(2)) and without (10 mg/m(2)) granulocyte-colony-stimulating factor (G-CSF). The dose-limiting toxicity (DLT) was febrile neutropenia. Two of 19 patients who were heterozygous for a polymorphism in the uridine diphosphate glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) gene (UGT1A1*28) developed DLTs (dose, 25 mg/m(2) with G CSF), and 2 patients who were homozygous for UGT1A1*28 were treated without DLTs (dose, 5 mg/m(2)). PK analysis indicated a mean terminal half-life of 19.4 +/- 3.4 hours. Sixteen patients (41%) achieved stable disease, including 6 of 39 patients (15%) who had stable disease that lasted >= 4 months. One patient with cholangiocarcinoma (no prior irinotecan) achieved a short-lived 32% tumor regression. Among 6 patients who had stable disease that lasted for >= 4 months, 3 had received prior irinotecan, and 1 had KRAS-positive colorectal cancer. CONCLUSIONS: EZN-2208 was well tolerated and produced stable disease that lasted for >= 4 months/unconfirmed partial responses in 7 of 39 heavily pretreated patients (18%) with advanced solid tumors, including those who had failed prior irinotecan therapy. PMID- 22674636 TI - Non-basic high-performance molecules for solution-processed organic solar cells. AB - A new small molecule, p-DTS(FBTTh(2))(2), is designed for incorporation into solution-fabricated high-efficiency organic solar cells. Of primary importance is the incorporation of electron poor heterocycles that are not prone to protonation and thereby enable the incorporation of commonly used interlayers between the organic semiconductor and the charge collecting electrodes. These features have led to the creation of p-DTS(FBTTh(2))(2)/PC(71)BM solar cells with power conversion efficiencies of up to 7%. PMID- 22674637 TI - Comparisons of CES-D depression scoring methods in two older adults ethnic groups. The emergence of an ethnic-specific brief three-item CES-D scale. AB - OBJECTIVE: To compare the reliabilities and convergent validities of five CES-D (Center for Epidemiologic Studies Depression) composite scores in two ethnic/racial groups of community-dwelling older adults. DESIGN: CES-D measurement equivalence was tested with Structural Equation Modeling in Puerto Rican (PR) and African American (AA) older adults, then reliabilities of five composite scores and their convergent validities were compared. FINDINGS: Bayesian CES-D scores had the highest reliabilities, followed by software estimated factor scores, the unit weight, and the weighted scores. Bayesian CES-D scores, factor scores, and surprisingly a group-specific three-item brief CES-D score exhibited better convergent validity than the unit-weight and weighted CES D scores. CONCLUSIONS: An ethnic group-specific three-item brief CES-D score emerged as a reliable CES-D measure in PR and AA older adults. We conclude that practitioners could emphasize three main symptoms in individual older adults in screening for depression, and researchers can model with confidence the relationships between the CES-D brief scale and its correlates. PMID- 22674638 TI - Pushing the limits of high-resolution functional MRI using a simple high-density multi-element coil design. AB - Recent studies have shown that functional MRI (fMRI) can be sensitive to the laminar and columnar organization of the cortex based on differences in the spatial and temporal characteristics of the blood oxygenation level-dependent (BOLD) signal originating from the macrovasculature and the neuronal-specific microvasculature. Human fMRI studies at this scale of the cortical architecture, however, are very rare because the high spatial/temporal resolution required to explore these properties of the BOLD signal are limited by the signal-to-noise ratio. Here, we show that it is possible to detect BOLD signal changes at an isotropic spatial resolution as high as 0.55 mm at 7 T using a high-density multi element surface coil with minimal electronics, which allows close proximity to the head. The coil comprises of very small, 1 * 2-cm(2) , elements arranged in four flexible modules of four elements each (16-channel) that can be positioned within 1 mm from the head. As a result of this proximity, tissue losses were five fold greater than coil losses and sufficient to exclude preamplifier decoupling. When compared with a standard 16-channel head coil, the BOLD sensitivity was approximately 2.2-fold higher for a high spatial/temporal resolution (1 mm isotropic/0.4 s), multi-slice, echo planar acquisition, and approximately three- and six-fold higher for three-dimensional echo planar images acquired with isotropic resolutions of 0.7 and 0.55 mm, respectively. Improvements in parallel imaging performance (geometry factor) were up to around 1.5-fold with increasing acceleration factor, and improvements in fMRI detectability (temporal signal-to noise ratio) were up to around four-fold depending on the distance to the coil. Although deeper lying structures may not benefit from the design, most fMRI questions pertain to the neocortex which lies within approximately 4 cm from the surface. These results suggest that the resolution of fMRI (at 7 T) can approximate levels that are closer to the spatial/temporal scale of the fundamental functional organization of the human cortex using a simple high density coil design for high sensitivity. PMID- 22674639 TI - Long-term effects of pelvic floor muscle training with vaginal cone in post menopausal women with urinary incontinence: a randomized controlled trial. AB - AIMS: The findings are limited about the long-term effects of treatment with vaginal cones in women with stress urinary incontinence (SUI). The aim of this study was to investigate the long-term effects of vaginal cones and pelvic floor muscle training in post-menopausal women with SUI. METHODS: This randomized controlled trial included 45 post-menopausal women with SUI. They were randomly allocated in three groups: vaginal cones (VC, n = 15), pelvic floor muscle training (PFMT, n = 15), and control group (CG, n = 15). Women in VC and PFMT groups were treated for 6 weeks with twice weekly sessions. Women in VC group carried out the pelvic floor muscle strengthening with vaginal cones. The CG did not receive any treatment during the corresponding time. Women were evaluated before treatment, at the end, 3 and 12 months after treatment completion for primary outcome (urinary leakage) and secondary outcomes (pelvic floor muscle strength, quality of life, satisfaction with treatment, and continuity of training). RESULTS: There was a significant decrease of urinary leakage in the VC and PFMT group comparing values at the end of treatment, 3 and 12 months to baseline values. There were no differences between VC and PFMT group in primary outcome in any evaluations. CONCLUSIONS: Treatments with and without vaginal cones can promote positive long-term effects on urinary leakage, pelvic floor muscle strength and quality of life in post-menopausal women with SUI in 6 weeks. PMID- 22674641 TI - Electron promotion by surface functional groups of single wall carbon nanotubes to overlying metal particles in a fuel-cell catalyst. AB - A remarkable promotion: Functional groups added onto single-wall carbon nanotubes (SWNTs) can significantly influence the activity of a noble metal for formic acid oxidation. Phenolate groups on SWNTs under alkaline conditions can double the activity of 20 % w/w Pd compared to unmodified SWNTs. This catalyst has 14 times higher activity than the commercial benchmark catalyst (10 % w/w Pd on Vulcan). PMID- 22674640 TI - Digit ratio 2D:4D in relation to autism spectrum disorders, empathizing, and systemizing: a quantitative review. AB - Prenatal testosterone (PT) effects have been proposed to increase systemizing (the drive to understand lawful input-output relationships), to decrease empathizing (the drive to understand others), and to cause autism via hypermasculinization of the brain. Digit ratio 2D:4D is a putative marker of PT effects in humans. An online study (n = 1896) into the relationship between the Reading the Mind in the Eyes Test (a widely used measure of empathizing) and self measured 2D:4D in a nonclinical sample is reported. No evidence for a link between empathizing and 2D:4D in either females or males emerged. Further, three meta-analyses are presented that look into the relationships of 2D:4D with autism spectrum disorder (ASD), systemizing, and empathizing. 2D:4D was substantially lower (more masculine) in ASD-affected individuals than in normal controls (d = 0.58, P < 0.001). However, 2D:4D was found to be virtually unrelated to systemizing and empathizing in normal adults. The results support the idea that high PT is a risk factor for autism, but they challenge the view that PT substantially contributes to sex differences in systemizing and empathizing. Possibly, this pattern reflects an interaction effect, whereby PT drives ASD characteristic changes only in brains with a specific damage. PMID- 22674642 TI - Modeling and prediction of subject accrual and event times in clinical trials: a systematic review. AB - BACKGROUND: Modeling and prediction of subject accrual and event times in clinical trials has been a topic of considerable interest for important practical reasons. It has implications not only at the initial planning stage of a trial but also on its ongoing monitoring. PURPOSE: To provide a systematic view of the recent research in the field of modeling and prediction of subject accrual and event times in clinical trials. METHODS: Two classes of methods for modeling and prediction of subject accrual are reviewed, namely, one that uses the Brownian motion and the other uses the Poisson process. Extensions of the accrual models in multicenter clinical trials are also discussed. Trials with survival endpoints require proper joint modeling of subject accrual and event/lost-to-follow-up (LTFU) times, the latter of which can be modeled either parametrically (e.g., exponential and Weibull) or nonparametrically. RESULTS: Flexible stochastic models are better suited when modeling real trials that does not follow constant underlying enrollment rate. The accrual model generally improves as center specific information is accounted for in multicenter trials. The choice between parametric and nonparametric event models can depend on confidence on the underlying event rates. LIMITATIONS: All methods reviewed in event modeling assume noninformative censoring, which cannot be tested. CONCLUSIONS: We recommend using proper stochastic accrual models, in combination with flexible event time models when applicable, for modeling and prediction of subject enrollment and event times in clinical trials. PMID- 22674643 TI - Prevalence of primary immune thrombocytopenia in Oklahoma. AB - To determine the prevalence of immune thrombocytopenia (ITP) in Oklahoma regardless of age, clinical characteristics, insurance status, and source of health care. Patients with ITP were identified by the administrative code ICD-9 CM 287.3 in Oklahoma hematologists' offices for a 2-year period, 2003-2004. Prevalence was estimated separately for children (<16 years old) and adults because of their distinct clinical characteristics. Oklahoma census data for 2000 was used as the denominator. Eighty-seven (94%) of 93 eligible Oklahoma hematologists participated; 620 patients with ITP were identified. The average annual prevalences were as follows: 8.1 (95% CI: 6.7-9.5) per 100,000 children, 12.1 (95% CI: 11.1-13.0) per 100,000 adults, and 11.2 (95% CI: 10.4-12.0) per 100,000 population. Among children and adults less than age 70 years, the prevalence was greater among women. Among adults aged 70 years and older, the prevalence was greater among men. The highest prevalence of ITP was among men age 80 years and older. These data document for the first time the prevalence of ITP regardless of age, clinical characteristics, insurance status, and source of health care. The methodology developed for this prevalence analysis may be adaptable for epidemiologic studies of other uncommon disorders which lack specific diagnostic criteria and are treated primarily by medical specialists. Am. J. Hematol. 2012. (c) 2012 Wiley Periodicals, Inc. PMID- 22674644 TI - Magnetic resonance imaging findings of true bifid mandibular condyle with duplicated mandibular fossa. AB - Bifid mandibular condyle (BMC) is a rare asymptomatic morphological alteration with no predilection for age group or gender. Its morphology varies from a shallow groove to two condylar heads with separate necks, oriented mediolaterally or anteroposteriorly. This report describes an unusual case of anteroposterior bifid condyle in a 39-year-old female patient with the main complaint of mouth opening limitation and a deviation of the mandible to the left side. Magnetic resonance imaging (MRI) findings revealed a bifid condyle on the left side and duplicated mandibular fossa, with the articular disc over the anterior head. The MRI images in the open-mouth position revealed minimal movement of the condyle. Despite the increased number of mediolateral bifid mandibular condyle cases described in the literature, none of previously reported cases of BMC included an anteroposterior bifid condyle case with two distinct mandibular fossa. PMID- 22674646 TI - High temporal and spatial resolution imaging of peripheral vascular malformations. AB - PURPOSE: To assess the performance of a recently developed 3D time-resolved CE MRA technique, Cartesian Acquisition with Projection-Reconstruction-like sampling (CAPR), for accurate characterization and treatment planning of vascular malformations of the periphery. MATERIALS AND METHODS: Twelve patient studies were performed (eight female, four male; average age, 33 years). The protocol consisted of three-dimensional (3D) time-resolved CE-MRA followed by a single late phase T1-weighted acquisition. Vascular malformations were imaged in the forearm, hand, thigh, and foot. Imaging evaluation was performed for accurate characterization of lesion type, identification of feeding and draining vessels, involvement with surrounding tissue, overall quality for diagnosis and treatment planning, and correlation with conventional angiography. RESULTS: Time-resolved CE-MRA allowed for characterization of malformation flow and type. Feeding and draining vessels were identified in all cases. Overall quality for diagnosis and treatment planning was 3.58/4.0, and correlation with conventional angiography was scored as 3.89/4.0. CONCLUSION: The CAPR time series has been shown to portray the temporal dynamics and structure of vascular malformations as well as the normal vasculature with high quality. CAPR time-resolved imaging is able to accurately characterize high and low flow lesions, allowing for pretreatment lesion assessment and treatment planning. Delayed imaging is important to capture complete filling of very slow flow vascular malformations. PMID- 22674647 TI - Free flap reconstruction in 1999 and 2009: changing case characteristics and outcomes. AB - OBJECTIVES/HYPOTHESIS: To compare free flap reconstructive cases from 1999 and 2009 with respect to patient characteristics, surgical characteristics, outcomes, and complications; and to discuss the evolution in free flap reconstruction at a single institution during this time period. STUDY DESIGN: Retrospective cohort comparison. METHODS: Free flap reconstruction cases from 1999 and 2009 were collected into two cohorts. Retrospective chart review was performed to extract patient characteristics, surgical characteristics, and outcomes. Cohorts were compared with respect to extracted data with statistical significance set at P < .05. RESULTS: There were 39 free flap reconstructions performed in 1999 and 81 performed in 2009. Patients in the 2009 cohort had higher American Society of Anesthesiologists scores and incidence of cardiovascular disease (P = .009 and .0045, respectively). Median operative time decreased from 12 hours in 1999 to 9 hours in 2009 (P < .0001). Median length of stay decreased from 14 to 9 days (P = .0006). The rate of perioperative return to the operating room to manage complications decreased from 30% to 17% (P = .103). There were five unsalvaged flap failures in 1999 (12.8%) compared to two failures in 2009 (2.5%) (P = .036). CONCLUSIONS: Patients undergoing free flap reconstruction are increasingly older and have more medical comorbidities. Despite these challenges, increased efficiency and teamwork stemming from accumulated institutional experience have led to decreased operative times, length of stay, and complication rates and increased overall success rates. PMID- 22674648 TI - Professor Bryan F Warren (15 April 1958-28 March 2012): an appreciation. PMID- 22674649 TI - Treatment of burn scars with the 1,550 nm nonablative fractional Erbium Laser. AB - BACKGROUND: Scarring is a major source of morbidity in patients with burns. Burn scars are difficult to treat and are among the worst scars seen in clinical medicine. Fractional laser resurfacing is a promising treatment option because of its unique wound healing response and depth of penetration. OBJECTIVE: To evaluate the efficacy of nonablative fractional resurfacing as a therapeutic option for extensive cutaneous scarring in burn patients. METHODS: Prospective, single-arm, pilot study. Ten subjects with second and third degree burn scars were treated with five nonablative fractional resurfacing treatments given at 4 week intervals. Three independent investigators evaluated subject outcomes at 3 months post-treatment (primary outcome); patients also provided subjective assessments of improvement (secondary outcome). RESULTS: Nonablative fractional resurfacing resulted in overall improvement in 90% of subjects, as determined by independent investigators; improvements were moderate to excellent in 60%. Ninety percent of subjects had improved skin texture, 80% had improved dyschromia, and 80% had improved hypertrophy/atrophy. Patients' self-reports also revealed moderate to excellent improvements (on average) in burn scar area, and significant improvements in self-esteem at 3 months post-treatment (P = 0.03). LIMITATIONS: Small sample size and lack of control group. CONCLUSIONS: Fractional resurfacing is a promising new treatment modality for burn scars. We should continue to identify novel approaches and management strategies for the spectrum of diverse burn scars so that we can better treat this patient population. PMID- 22674651 TI - Prevalence of dermatitis in the working population, United States, 2010 National Health Interview Survey. AB - BACKGROUND: Prevalence patterns of dermatitis among workers offer clues about risk factors and targets for prevention, but population-based estimates of the burden of dermatitis among US workers are lacking. METHODS: Data from an occupational health supplement to the 2010 National Health Interview Survey (NHIS OHS) were used to estimate the prevalence of dermatitis overall and by demographic characteristics and industry and occupation (I&O) of current/recent employment. RESULTS: Data were available for 27,157 adults, including 17,524 current/recent workers. The overall prevalence rate of dermatitis among current/recent workers was 9.8% (range among I&O groups: 5.5-15.4%), representing approximately 15.2 million workers with dermatitis. The highest prevalence rates were among I&O groups related to health care. Overall, 5.6% of dermatitis cases among workers (9.2% among healthcare workers) were attributed to work by health professionals. CONCLUSIONS: Dermatitis affected over 15 million US workers in 2010, and its prevalence varied by demographic characteristics and industry and occupation of employment. The prevalence rate of work-related dermatitis based on the NHIS-OHS was approximately 100-fold higher than incidence rates based on the Bureau of Labor Statistics' Survey of Occupational Illness and Injury. PMID- 22674650 TI - Primary visual response (M100) delays in adolescents with FASD as measured with MEG. AB - Fetal alcohol spectrum disorders (FASD) are debilitating, with effects of prenatal alcohol exposure persisting into adolescence and adulthood. Complete characterization of FASD is crucial for the development of diagnostic tools and intervention techniques to decrease the high cost to individual families and society of this disorder. In this experiment, we investigated visual system deficits in adolescents (12-21 years) diagnosed with an FASD by measuring the latency of patients' primary visual M100 responses using MEG. We hypothesized that patients with FASD would demonstrate delayed primary visual responses compared to controls. M100 latencies were assessed both for FASD patients and age matched healthy controls for stimuli presented at the fovea (central stimulus) and at the periphery (peripheral stimuli; left or right of the central stimulus) in a saccade task requiring participants to direct their attention and gaze to these stimuli. Source modeling was performed on visual responses to the central and peripheral stimuli and the latency of the first prominent peak (M100) in the occipital source timecourse was identified. The peak latency of the M100 responses were delayed in FASD patients for both stimulus types (central and peripheral), but the difference in latency of primary visual responses to central vs. peripheral stimuli was significant only in FASD patients, indicating that, while FASD patients' visual systems are impaired in general, this impairment is more pronounced in the periphery. These results suggest that basic sensory deficits in this population may contribute to sensorimotor integration deficits described previously in this disorder. PMID- 22674652 TI - 18F-FDG PET/CT for detecting distant metastases in patients with recurrent head and neck squamous cell carcinoma. AB - BACKGROUND: Distant metastases (DMs) increase in patients with recurrent head and neck squamous cell carcinoma (HNSCC). We evaluated the ability of fluorine 18 fluorodeoxyglucose ((18) F-FDG) positron emission tomography/computed tomography (PET/CT) to detect DMs in these patients. METHOD: We evaluated 82 consecutive patients with histologically confirmed recurrent HNSCC. Patients with previous DMs were excluded. All patients received whole-body (18) F-FDG PET/CT scanning for restaging of recurrent HNSCC and follow-up after salvage surgery. Any suspected DMs were confirmed by histology and further imaging workups. The diagnostic ability of (18) F-FDG PET/CT to detect DMs was assessed. RESULTS: Of the 82 patients, 14 (17%) had DMs. The lung (93%) and bone (43%) were the most frequent metastatic sites. (18) F-FDG PET/CT correctly diagnosed the presence of DMs in 12 of 14 patients and their absence in 57 of 68 patients. The sensitivity, specificity, accuracy, and positive (PPV) and negative predictive values (NPV) of (18) F-FDG PET/CT for detecting DMs were 86% (95% confidence interval, 57-98%), 84% (72-91%), 84% (74-91%), 52% (30-73%), and 97% (88-99%), respectively. CONCLUSIONS: (18) F-FDG PET/CT may be useful in the detection of DMs prior to and after salvage surgery in the high-risk patients with recurrent HNSCC. PMID- 22674653 TI - Formulas used by Tibetan doctors at Men-Tsee-Khang in India for the treatment of neuropsychiatric disorders and their correlation with pharmacological data. AB - The aim of the present study was to identify formulas used at Men-Tsee-Khang (Tibetan Medical and Astrological Institute), India, for the treatment of neuropsychiatric disorders and to compare the Tibetan usage of particular ingredients with pharmacological data from the scientific database. Using ethnographic methods, five doctors were selected and interviewed. A correlation was observed between central nervous system disorders and rLung, one of the three humors in Tibetan medicine, which imbalance is the source of mental disorders, and ten multi-ingredient formulas used to treat the imbalance of this particular humor were identified. These formulas utilize 61 ingredients; among them were 48 plant species. Each formula treats several symptoms related to rLung imbalance, so the plants may have therapeutic uses distinct from those of the formulas in which they are included. Myristica fragrans, nutmeg, is contained in 100% of the formulas, and its seeds exhibit stimulant and depressant actions affecting the central nervous system. Preclinical and clinical data from the scientific literature indicate that all of the formulas include ingredients with neuropsychiatric action and corroborate the therapeutic use of 75.6% of the plants. These findings indicate a level of congruence between the therapeutic uses of particular plant species in Tibetan and Western medicines. PMID- 22674654 TI - How is flow experienced and by whom? Testing flow among occupations. AB - The aims of this paper are to test (1) the factorial structure of the frequency of flow experience at work; (2) the flow analysis model in work settings by differentiating the frequency of flow and the frequency of its prerequisites; and (3) whether there are significant differences in the frequency of flow experience depending on the occupation. A retrospective study among 957 employees (474 tile workers and 483 secondary school teachers) using multigroup confirmatory factorial analyses and multiple analyses of variance suggested that on the basis of the flow analysis model in work settings, (1) the frequency of flow experience has a two-factor structure (enjoyment and absorption); (2) the frequency of flow experience at work is produced when both challenge and skills are high and balanced; and (3) secondary school teachers experience flow more frequently than tile workers. PMID- 22674655 TI - Surface functionalization of nanoparticles to control cell interactions and drug release. AB - Nanoparticles made from poly(dl-lactide-co-glycolide) (PLGA) are used to deliver a wide range of bioactive molecules, due to their biocompatibility and biodegradability. This study investigates the surface modification of PLGA nanoparticles via the layer-by-layer (LbL) deposition of polyelectrolytes, and the effects of these coatings on the release behavior, cytotoxicity, hemolytic activity, and cellular uptake efficiency. PLGA nanoparticles are modified via LbL adsorption of two polyelectrolyte pairs: 1) poly(allylamine hydrochloride) (PAH) and poly(styrene sulfonate) (PSS) and 2) poly(L-lysine hydrobromide) (PLL) and dextran sulfate (DES). It is demonstrated that both PAH/PSS and PLL/DES coatings suppress the burst release usually observed for unmodified PLGA nanoparticles and that the release behavior can be adjusted by changing the layer numbers, layer materials, or by crosslinking the layer constituents. Neither bare nor polyelectrolyte-modified PLGA nanoparticles show any signs of cytotoxicity. However, nanoparticles with a positively charged polyelectrolyte as the outermost layer induce hemolysis, whereas uncoated particles or particles with a negatively charged polyelectrolyte as the outermost layer show no hemolytic activity. Furthermore, particles with either PAH or PLL as the outermost layer also demonstrate a higher uptake efficiency by L929 fibroblast cells, due to a higher cell-particle affinity. This study suggests that LbL coating of PLGA nanoparticles can control the release behavior of bioactive molecules as well as the surface activity, therefore providing a promising strategy to enhance the efficiency of nanoparticulate drug-delivery systems. PMID- 22674656 TI - Biases and errors on allele frequency estimation and disease association tests of next-generation sequencing of pooled samples. AB - Next-generation sequencing is widely used to study complex diseases because of its ability to identify both common and rare variants without prior single nucleotide polymorphism (SNP) information. Pooled sequencing of implicated target regions can lower costs and allow more samples to be analyzed, thus improving statistical power for disease-associated variant detection. Several methods for disease association tests of pooled data and for optimal pooling designs have been developed under certain assumptions of the pooling process, for example, equal/unequal contributions to the pool, sequencing depth variation, and error rate. However, these simplified assumptions may not portray the many factors affecting pooled sequencing data quality, such as PCR amplification during target capture and sequencing, reference allele preferential bias, and others. As a result, the properties of the observed data may differ substantially from those expected under the simplified assumptions. Here, we use real datasets from targeted sequencing of pooled samples, together with microarray SNP genotypes of the same subjects, to identify and quantify factors (biases and errors) affecting the observed sequencing data. Through simulations, we find that these factors have a significant impact on the accuracy of allele frequency estimation and the power of association tests. Furthermore, we develop a workflow protocol to incorporate these factors in data analysis to reduce the potential biases and errors in pooled sequencing data and to gain better estimation of allele frequencies. The workflow, Psafe, is available at http://bioinformatics.med.yale.edu/group/. PMID- 22674657 TI - Tramadol enhances urethral continence function through u-opioid receptors in rats. AB - AIMS: (+/-)-Tramadol hydrochloride (tramadol) is a widely used analgesic that stimulates the u-opioid receptor and inhibits the reuptake of serotonin and noradrenalin. Although tramadol is also known to inhibit the micturition reflex in rats, its effects on urethral continence function have not been reported. We therefore examined whether intravenous tramadol (1, 3, and 10 mg/kg) affects intraurethral pressure, bladder leak point pressure, and leak volume in urethane anesthetized female rats. METHODS: (1) The intraurethral pressure was recorded with a microtip pressure transducer placed at the maximum pressure zone of the intrinsic urethral sphincter. (2) Gentle pressure was directly applied to the saline-filled bladder with a cotton bud until leakage occurred, and the bladder pressure at the moment of leakage was taken as the bladder leak point pressure. (3) The leak volume was measured as the amount of fluid leakage from the urethral orifice after electrical stimulation of abdominal muscles. RESULTS: Tramadol significantly increased the intraurethral pressure. Both tramadol and morphine increased the bladder leak point pressure and decreased the leak volume. These changes were reversed by subcutaneous pretreatment with naloxone. CONCLUSIONS: Tramadol improved urethral function and inhibited urinary incontinence through u opioid receptors. PMID- 22674658 TI - TiO2 composing with pristine, metallic or semiconducting single-walled carbon nanotubes: which gives the best performance for a dye-sensitized solar cell. AB - Different types of single-walled carbon nanotubes (SWCNTs), pristine (p-), metallic (m-) and semiconducting (s-) are incorporated into TiO(2) photoanodes to improve the dye-sensitized solar-cell (DSSC) performance and their effects on the device performance are further investigated. Although all three types of SWCNTs are found to have comparable structural morphologies and a reduced charge transport resistivity for the photoanodes, only the semiconducting one was able to suppress charge-recombination events, resulting in even greater improvement of DSSC performances. This is very likely to be ascribed to the higher energy barrier of s-SWCNTs compared to both m- and p-SWCNTs to block the back flowing of dye-injected electrons for I(3)(-) reduction in the charge recombination process. PMID- 22674659 TI - ZnO hollow spheres with double-yolk egg structure for high-performance photocatalysts and photodetectors. AB - Inspired by opening soft drink cans, a one-pot method to prepare ZnO hollow spheres with double-yolk egg (DEH) architectures is developed. The bubble assisted Ostwald ripening is proposed for the formation of these novel structures. Uniqueness of DEHs morphology led to greatly enhanced photocatalytic activity and photodetector performance. The newly developed synthetic concept and the obtained novel morphologies should pave the way towards the design and fabrication of other similar materials with enhanced properties for microelectronics, optoelectronics, and other applications. PMID- 22674660 TI - A pilot study of segmental mandibulectomy with surgical navigation using fluorine 18 fluorodeoxyglucose positron-emission tomography/computed tomography. AB - OBJECTIVES/HYPOTHESIS: To evaluate the efficacy of treating lower gum cancer using fluorine-18 fluorodeoxyglucose positron-emission tomography/computed tomography ([18] F-FDG PET/CT) surgical navigation to control bony margins during segmental mandibulectomy. STUDY DESIGN: This study was conducted between September 2010 and June 2011 in a tertiary referral center in southern Taiwan. METHODS: Segmental mandibulectomy was performed using surgical navigation via [18] F-FDG PET/CT. Bony margins after decalcification, the 1-year survival rate, and local control rate were evaluated. RESULTS: Ten cases of advanced lower gum cancer in male patients were treated by mandibulectomy, and the bony margins required to excise all neoplastic cells were negative in all cases by using surgical navigation. The minimal distance from the tumor border to the bony incision was 2 cm (2.0-2.9 cm). The mean follow-up period was 15.2 months (range, 6-24 months) with a 1-year survival rate of 90% and local control rate of 100%. CONCLUSIONS: The segmental mandibulectomy aided by surgical navigation with [18] F-FDG PET/CT guidance is simple and feasible to ensure adequate bony margins intraoperatively, but more patients are necessary to support these findings. PMID- 22674661 TI - Jahn-Teller distortion of hydrocarbon cations probed by infrared photodissociation spectroscopy. PMID- 22674662 TI - Anatomical planes: are we teaching accurate surface anatomy? AB - Anatomical planes used in clinical practice and teaching anatomy are largely derived from cadaver studies. Numerous inconsistencies in clinically important surface markings exist between and within anatomical reference texts. The aim of this study was to reassess the accuracy of common anatomical planes in vivo using computed tomographic (CT) imaging. CT scans of the trunk in supine adults at end tidal inspiration were analyzed by dual consensus reporting to determine the anatomy of five anatomical planes: sternal angle, transpyloric, subcostal, supracristal, and the plane of the pubic crest. Patients with kyphosis, scoliosis, or abnormal lordosis, distorting space-occupying lesions, or visceromegaly were excluded. Among 153 thoracic CT scans (mean age 63 years, 53% female), the sternal angle was most common at T4 (females) or T4/5 (males) vertebral level, and the tracheal bifurcation, aortic arch, and pulmonary trunk were most often below this plane. In 108 abdominal CT scans (mean age 60 years, 59% female), the subcostal and supracristal planes were most often at L2 (58%) and L4 (69%), respectively. In 52 thoracoabdominal CT scans (mean age 61 years, 56% female), the transpyloric plane was between lower L1 and upper L2 (75%); in this plane were the superior mesenteric artery (56%), formation of the portal vein (53%), tip of the ninth rib (60%), and the left renal hilum (54%), but the right renal hilum and gallbladder fundus were more often below. The surface anatomy of anatomical planes needs revising in the light of results from living subjects using modern imaging techniques. PMID- 22674663 TI - Multiexponential T(2) analyses in a murine model of hepatic fibrosis at 11.7 T MRI. AB - This study evaluated the effects of hepatic fibrosis on the multiexponential T(2) (MET(2) ) relaxation of ex vivo murine liver specimens using an 11.7 T MRI. This animal study was approved by the Institutional Animal Care and Use Committee. Eighteen male C57BL/6 mice were divided into control (n = 3) and experimental (n = 15) groups; the latter group was fed a 3,5-dicarbethoxy-1,4-dihydrocollidine supplemented diet to induce hepatic fibrosis. Ex vivo liver specimens were imaged using an 11.7 T MRI scanner. A multi-echo spin-echo sequence was utilized for subsequent MET(2) analysis. Degrees of fibrosis were determined by a pathologist, as well as by digital image analysis. Scatterplot graphs comparing various features of the MET(2) signal decay with the degrees of fibrosis were generated, and correlation coefficients were calculated. Two distinct peaks of the MET(2) signal decay were identified in all liver specimens: a short T(2) component with a geometric mean T(2) (GMT(2) ) approximating 30 ms; and a long T(2) component with GMT(2) approximating 400 ms. Strong correlation was found between the degree of hepatic fibrosis and the amplitude of the short T(2) component, with a higher degrees of fibrosis associated with a lower amplitude. Moderate correlation was also found between hepatic fibrosis and the GMT(2) values of the long T(2) component, with higher degrees of fibrosis associated with lower GMT(2) values. The study of hepatic microenvironments using MET(2) analyses offers potential utility in the ongoing development of the noninvasive assessment of hepatic fibrosis using MRI. PMID- 22674664 TI - High use of tramadol in Germany: an analysis of statutory health insurance data. AB - PURPOSE: Tramadol is a weak opioid according to the World Health Organization pain ladder step II. It is one of the most prescribed analgesic substances in Germany, but tramadol and the step II opioids are very controversially discussed. We analysed patients with filled tramadol prescriptions with special emphasis on high use. METHODS: We used data from a German statutory health insurance for the year 2007. Patients older than 17 years with at least one tramadol prescription were analysed concerning demographic data, pain diagnoses, comorbidities, concomitant opioids, physician contacts and number of different prescribed substances. We fitted a logistic regression model to find relevant associations with high use (defined as >180 daily defined doses per year). RESULTS: From 22 ,946 insurants with filled tramadol prescriptions, 7.9% (n = 1812) are identified as high users; 90.9% of all tramadol patients and 93.1% of the high users have at least one pain diagnosis. The most frequent diagnoses are back pain (78.4% vs 77.1%) and arthritis pain (37.9% vs 41.8%). The results of the logistic regression model show associations between high use of tramadol and rising age, unspecific pain diagnoses, psychiatric co-morbidities, additional prescribed strong opioids and a high number of physician contacts. CONCLUSIONS: Despite some limitations, this study shows the prescriptions of tramadol in Germany in an authentic way. It seems that there are some 'challenging' patients that present a treatment dilemma for some prescribers. This might result in a high use of tramadol. PMID- 22674666 TI - How feasible is implementation of distress screening by cancer clinicians in routine clinical care? AB - BACKGROUND: There is considerable uncertainty regarding the acceptability of routine distress screening. METHODS: In an unfunded implementation study, the authors asked 50 clinicians (chemotherapy nurses and treatment radiographers/radiation technologists) to implement a screening program for distress as part of routine care and to record their feedback after each clinical encounter. In total, 379 patients were screened using a simple paper-and-pencil versions of distress thermometer and the emotion thermometer (ET). RESULTS: Across all screening applications, clinicians believed that screening was useful during 43% of assessments and was not useful during 35.9% of assessments, and they were unsure or neutral in 21.1% of assessments. The application of the screening program assisted staff in changing their clinical opinion after 41.9% of assessments, and clinicians believed that the screening program helped with communication in >50% of assessments. However, 37.5% believed that screening was impractical for routine use, and more chemotherapy nurses than radiographers rated the screening program as "not useful." On multivariate analysis, 3 variables were associated with high staff satisfaction with screening, namely, receipt of prior training, talking with the patient about psychosocial issues, and improved detection of psychological problems. A favorable perception of screening also was linked to a change in clinical opinion. CONCLUSIONS: Opinions of cancer clinicians regarding routine distress screening were mixed: Approximately 33% considered screening not useful/impractical, whereas >50%n believed promoted good communication and/or helped with recognition. Clinicians who were more positive about screening gained greater benefits from screening in terms of communication and recognition. PMID- 22674665 TI - Characterization of allergens and airborne fungi in low and middle-income homes of primary school children in Durban, South Africa. AB - BACKGROUND: The South Durban Health Study (SDHS) is a population-based study that examined the relationship between exposure to ambient air pollutants and respiratory disease among school children with high prevalence of asthma who resided in two purposely selected communities in north and south Durban, KwaZulu Natal, South Africa. METHODS: From the SDHS participants, a subgroup of 135 families was selected for investigation of household characteristics potentially related to respiratory health. In these households, a walkthrough investigation was conducted, and settled dust and air samples were collected for allergen and fungal measurements using standardized techniques. RESULTS: Asp f1 allergen was detected in all homes, and Bla g1 allergen was detected in half of the homes. House dust allergens, Der f1 and Der p1 exceeded concentrations associated with risk of sensitization and exacerbation of asthma in 3% and 13%, respectively, of the sampled homes, while Bla g1 exceeded guidance values in 13% of the homes. Although airborne fungal concentrations in sleep areas and indoors were lower than outdoor concentrations, they exceeded 1,000 CFU/m(3) in 29% of the homes. Multivariate analyses identified several home characteristics that were predictors of airborne fungal concentrations, including moisture, ventilation, floor type, and bedding type. Airborne fungal concentrations were similar indoors and outdoors, which likely reduced the significance of housing and indoor factors as determinants of indoor concentrations. CONCLUSION: Allergen concentrations were highly variable in homes, and a portion of the variability can be attributed to easily recognized conditions. PMID- 22674667 TI - Molecular characterization, recombinant protein expression, and mRNA analysis of type 3 von Willebrand disease: Studies of an Italian cohort of 10 patients. AB - Type 3 von Willebrand disease (VWD3) is characterized by unmeasurable von Willebrand factor (VWF) levels in plasma and platelets and severe but variable hemorrhagic symptoms. To identify and characterize the causal mutations, we screened 10 Italian patients with VWD3 by several techniques including Multiplex Ligation-dependent Probe Amplification to identify large insertions and deletions, High Resolution Melting and PCR coupled with Sanger sequencing. Fourteen different mutations scattered throughout the VWF gene were identified, 10 of which were novel. As expected, most of these mutations caused null alleles: five were deletions (del exons 1-3, del exon 17, c.2157delA, c.2269delCT, and c.3940delG), three nonsense (p.Q1526X, p.E1549X, and p.C2448X) and three potential splice-site mutations (c.658-2A>G, c.7729+7C>T, and c.8155+1G>T). Three candidate missense mutations (p.C2184S, p.C2212R, and p.C2325S) were also identified. Missense mutations and the putative splice-site defects were confirmed to be disease related by in vitro expression studies and mRNA analysis. None of these patients have developed alloantibodies against VWF. This study extends our previous finding that most of the mutations that we identified in VWD3 patients arise independently and are scattered throughout the entire VWF gene. PMID- 22674668 TI - Heart-beat-phase-coherent Doppler optical coherence tomography for measuring pulsatile ocular blood flow. AB - We introduce a Doppler OCT (DOCT) platform that is fully synchronized with the heart-beat via a pulse oximeter. The system allows reconstructing heart-beat phase-coherent quantitative DOCT volumes. The method is to acquire a series of DOCT volumes and to record the pulse in parallel. The heartbeat data is used for triggering the start of each DOCT volume acquisition. The recorded volume series is registered to the level of capillaries using a cross-volume registration. The information of the pulse phase is used to rearrange the tomograms in time, to obtain a series of phase coherent DOCT volumes over a pulse. We present Doppler angle independent quantitative evaluation of the absolute pulsatile blood flow within individual retinal vessels as well as of the total retinal blood flow over a full heartbeat cycle. PMID- 22674670 TI - Natural bactericidal surfaces: mechanical rupture of Pseudomonas aeruginosa cells by cicada wings. AB - Natural superhydrophobic surfaces are often thought to have antibiofouling potential due to their self-cleaning properties. However, when incubated on cicada wings, Pseudomonas aeruginosa cells are not repelled; instead they are penetrated by the nanopillar arrays present on the wing surface, resulting in bacterial cell death. Cicada wings are effective antibacterial, as opposed to antibiofouling, surfaces. PMID- 22674669 TI - Same but different: 9-month-old infants at average and high risk for autism look at the same facial features but process them using different brain mechanisms. AB - The study examined whether 9-month-old infants at average vs. high risk for autism spectrum disorder (ASD) process facial features (eyes, mouth) differently and whether such differences are related to infants' social and communicative skills. Eye tracking and visual event-related potentials (ERPs) were recorded in 35 infants (20 average-risk typical infants, 15 high-risk siblings of children with ASD) while they viewed photographs of a smiling unfamiliar female face. On 30% of the trials, the eyes or the mouth of that face was replaced with corresponding features from a different female. There were no group differences in the number, duration, or distribution of fixations, and all infants looked at the eyes and mouth regions equally. However, increased attention to the mouth was associated with weaker receptive communication skills and increased attention to the eyes correlated with better interpersonal skills. ERP results revealed that all infants detected eye and mouth changes but did so using different brain mechanisms. Changes in facial features were associated with changes in activity of the face perception mechanisms (N290) for the average-risk group but not for the high-risk infants. For all infants, correlations between ERP and eye-tracking measures indicated that larger and faster ERPs to feature changes were associated with fewer fixations on the irrelevant regions of stimuli. The size and latency of the ERP responses also correlated with parental reports of receptive and expressive communication skills, suggesting that differences in brain processing of human faces are associated with individual differences in social-communicative behaviors. PMID- 22674671 TI - Efficient determination of purine metabolites in brain tissue and serum by high performance liquid chromatography with electrochemical and UV detection. AB - The purine metabolic pathway has been implicated in neurodegeneration and neuroprotection. High-performance liquid chromatography (HPLC) is widely used to determine purines and metabolites. However, methods for analysis of multiple purines in a single analysis have not been standardized, especially in brain tissue. We report the development and validation of a reversed-phase HPLC method combining electrochemical and UV detection after a short gradient run to measure seven purine metabolites (adenosine, guanosine, inosine, guanine, hypoxanthine, xanthine and urate) from the entire purine metabolic pathway. The limit of detection (LoD) for each analyte was determined. The LoD using UV absorption was 0.001 mg/dL for hypoxanthine (Hyp), inosine (Ino), guanosine (Guo) and adenosine (Ado), and those using coulometric electrodes were 0.001 mg/dL for guanine (Gua), 0.0001 mg/dL for urate (UA) and 0.0005 mg/dL for xanthine (Xan). The intra- and inter-day coefficient of variance was generally <8%. Using this method, we determined basal levels of these metabolites in mouse brain and serum, as well as in post-mortem human brain. Peak identities were confirmed by enzyme degradation. Spike recovery was performed to assess accuracy. All recoveries fell within 80 120%. Our HPLC method provides a sensitive, rapid, reproducible and low-cost method for determining multiple purine metabolites in a single analysis in serum and brain specimens. PMID- 22674672 TI - Use of NMR in fish processing optimization: a review of recent progress. AB - The goal of this review is to give an overview of general trends in the application of the NMR related to fish processing and quality and to provide some viewpoints on the current situation. Three novel examples of the application of the methodologies magnetic resonance spectroscopy, magnetic resonance imaging, and low-field NMR are also presented. The capability of these techniques to be utilized as a tool to optimize fish processing, and thereby improving product quality, as well as to confirm labelling information, are demonstrated. PMID- 22674673 TI - Sleep spindles predict neural and behavioral changes in motor sequence consolidation. AB - The purpose of this study was to investigate the predictive function of sleep spindles in motor sequence consolidation. BOLD responses were acquired in 10 young healthy subjects who were trained on an explicitly known 5-item sequence using their left nondominant hand, scanned at 9:00 pm while performing that same task and then were retested and scanned 12 h later after a night of sleep during which polysomnographic measures were recorded. An automatic algorithm was used to detect sleep spindles and to quantify their characteristics (i.e., density, amplitude, and duration). Analyses revealed significant positive correlations between gains in performance and the amplitude of spindles. Moreover, significant increases in BOLD signal were observed in several motor-related areas, most of which were localized in the right hemisphere, particularly in the right cortico striatal system. Such increases in BOLD signal also correlated positively with the amplitude of spindles at several derivations. Taken together, our results show that sleep spindles predict neural and behavioral changes in overnight motor sequence consolidation. PMID- 22674674 TI - Use of magnetic resonance imaging in prenatal prognosis of the fetus with isolated left congenital diaphragmatic hernia. AB - OBJECTIVES: To investigate the prognostic value of magnetic resonance-calculated fetal lung volumes (FLV) in fetuses with isolated left congenital diaphragmatic hernia (L-CDH) who receive standardized prenatal and postnatal care at a single institution. MATERIALS AND METHODS: A retrospective review was undertaken to identify fetuses with isolated L-CDH between 2001 and 2010. RESULTS: Eighty-five cases of isolated L-CDH were identified. The overall survival was 65% (55/85). Survival was 45% if there was 'liver up' (23/51) and 94% if there was 'liver down' (32/34). Univariate statistical analysis showed that 'liver up' (p=0.001), lung-to-head ratio (LHR) at diagnosis (p=0.009), observed/expected (O/E) LHR (p=0.01), total FLV (p=0.03), right LV (p=0.04), magnetic resonance imaging (MRI) observed versus expected (O/E) FLV (p=0.002), intrathoracic versus intraabdominal stomach (p=0.002), percentage of herniated liver (p=0.004), and postnatal extracorporeal membrane oxygenation use (p=0.001) are predictive of postnatal survival. Multivariate analysis of only prenatal factors showed that the most important determinants of postnatal outcome are percentage of herniated liver, presence of liver up, and MRI O/E FLV. CONCLUSION: Herniated intrathoracic liver expressed as 'liver up' or as percent herniated liver and MRI measurement of FLV expressed as a O/E ratio are strong prenatal indicators of postnatal survival. PMID- 22674675 TI - Chlorogenic acid exhibits cholesterol lowering and fatty liver attenuating properties by up-regulating the gene expression of PPAR-alpha in hypercholesterolemic rats induced with a high-cholesterol diet. AB - Hypercholesterolemia is a major risk factor for the development of cardiovascular disease and nonalcoholic fatty liver disease. Natural compounds have been proved to be useful in lowering serum cholesterol to slow down the progression of cardiovascular disease and nonalcoholic fatty liver disease. In the present study, the hypocholesterolemic and hepatoprotective effects of the dietary consumption of chlorogenic acid were investigated by monitoring plasma lipid profile (total cholesterol, triglycerides, high-density lipoprotein and low density lipoprotein) in Sprague-Dawley rats fed with a normal diet, a high cholesterol diet or a high-cholesterol diet supplemented with chlorogenic acid (1 or 10 mg/kg/day p.o.) for 28 days. Chlorogenic acid markedly altered the increased plasma total cholesterol and low-density lipoprotein but decreased high density lipoprotein induced by a hypercholesterolemic diet with a dose-dependent improvement on both atherogenic index and cardiac risk factor. Lipid depositions in liver were attenuated significantly in hypercholesterolemic animals supplemented with chlorogenic acid. It is postulated that hypocholesterolemic effect is the primary beneficial effect given by chlorogenic acid, which leads to other secondary beneficial effects such as atheroscleroprotective, cardioprotective and hepatoprotective functions. The hypocholesterolemic functions of chlorogenic acid are probably due to the increase in fatty acids unitization in liver via the up-regulation of peroxisome proliferation-activated receptor alpha mRNA. PMID- 22674676 TI - Bony pelvis dimensions in women with and without stress urinary incontinence. AB - AIMS: To test the null hypothesis that bony pelvis dimensions are similar in women with and without stress urinary incontinence (SUI), both in the postpartum and midlife periods. METHODS: Secondary analyses were performed of two case control studies comparing women with SUI to asymptomatic controls. One study examined primiparas in the first 9-12 months postpartum; the other study involved middle-aged women. SUI was confirmed by full-bladder stress test. All subjects underwent pelvic magnetic resonance imaging. The interspinous and intertuberous diameters, subpubic angle, and sacrococcygeal joint-to-the inferior pubic point distance were measured from the images independently by two authors. RESULTS: In the young cohorts, we compared primiparas with de novo postpartum SUI to both continent primiparas and nulliparas. Postpartum SUI is associated with a wider subpubic angle. There is also a trend towards wider interspinous and intertuberous diameters in the stress-incontinent primiparas as compared to the continent cohorts, although this did not reach statistical significance with our sample sizes. By contrast, no significant differences in bony pelvis dimensions were identified when comparing middle-aged women with SUI and their continent controls. CONCLUSIONS: Bony pelvis dimensions are different in women with SUI than in matched continent controls. However, these differences are only identified in young primiparas in the postpartum period, not in middle-aged women. PMID- 22674677 TI - Effects of chewing menthol gum on the alertness of healthy volunteers and those with an upper respiratory tract illness. AB - Recent research has shown that chewing gum increases subjective alertness. Upper respiratory tract illnesses (URTIs) lead to reduced alertness, and it has been shown that stimulants such as caffeine can reverse this effect. It is now important to determine whether menthol chewing gum can produce a similar effect. Young adults with an URTI (N = 16) and a healthy control group (N = 12) rated their mood and symptoms on two occasions (the first when those with a URTI were ill and the second when both groups were healthy). During each session, volunteers provided a rating while chewing gum and when they were not chewing. Those with a URTI reported reduced alertness, which persisted into convalescence. Chewing gum was associated with greater alertness in both those with URTIs and the healthy group. Chewing gum reduced the severity of nasal symptoms in those with a cold. The effects of the URTI and menthol gum may reflect changes in trigeminal stimulation. PMID- 22674680 TI - In vivo predictive release methods for medicated chewing gums. AB - Understanding the performance of a drug product in vivo plays a key role in the development of meaningful in vitro drug release methodology. In case of functional chewing gums, the mode and the mechanism of release and the site of application differ significantly from other conventional solid oral dosage forms and require a special consideration to extract meaningful information from clinical studies. In the current study, suitable drug release methodology was developed to predict the in vivo performance of an investigated chewing gum product. Different parameters of the drug release testing apparatus described in the Ph. Eur. and Pharmeuropa were evaluated. Drug release data indicate that the parameters, chewing distance, chewing frequency and twisting motion, affect the drug release. Higher drug release was observed when the frequency was changed from 40 chews/min to 60 chews/min for apparatus A and B, as was the case for the twisting motion when changed from 20o to 40o for apparatus B. As far as the chewing distance is concerned, the release rate was in the following order; apparatus A: 0.3 mm > 0.5 mm > 0.7 mm; apparatus B: 1.4 mm > 1.6 mm > 1.8 mm. A suitable apparatus set-up for in vitro release testing was identified. The method will be useful for the establishment of in vitro in vivo correlations (IVIVC) for medicated chewing gums. Interchangeability of the apparatus for a product is not generally recommended without prior knowledge of the performance of the product, as the construction and principle of operation for the apparatus differ considerably. PMID- 22674681 TI - Ribbons, vesicles, and baskets: supramolecular assembly of a coil-plate-coil emeraldicene derivative. AB - Concentration matters: the self-assembly of title compound 1 evolves from well defined ribbons to vesicles to baskets, upon simply decreasing the concentration of 1 in tetrahydrofuran. Electron microscopy revealed a unique self-assembled structure: baskets are formed by curved and self-wrapped nanometer-thin ribbons. The self-assembly of pi-conjugated molecule 1 enables to construct nano/micro structures with desired optoelectronic properties. PMID- 22674682 TI - Assessment of diffraction-enhanced synchrotron imaging for cartilage degeneration of the human knee joint. AB - Diffraction-enhanced imaging (DEI) is a radiographic technology that harnesses the X-ray refraction and scatter rejection properties that are not available with conventional radiography. Here, we test the efficacy of planar DEI to render images from which cartilage degeneration, characteristic of osteoarthritis, can be detected. DEI was carried out on human cadaveric intact knee joints at the X 15 beamline at the National Synchrotron Light Source. The gross specimens and the DEI images were graded separately for levels of cartilage degeneration on six individual surfaces: anterior and posterior femoral and tibial on both medial and lateral sides. There was a significant correlation between the actual levels of cartilage degeneration and what was observed in their respective DEI images (P < 0.05) for all six articular surfaces. Some articular surfaces (patellar surfaces, in particular) could not be visualized because of overlap with superimposed bone. Sensitivity for the graded articular surfaces was 0.73 and specificity was 0.92 (Grade 0 being no lesion and Grades 1-6 being increasing gradations of lesions). Chondrocalcinosis was also observed in DEI images to a far greater extent compared with the conventional radiographs. DEI renders images that are significantly correlated with their actual gross morphology. Detection of lesions was better for more severe grades of degeneration than for partial focal lesions. Although some articular surfaces could not be visualized because of superimposed bone, we feel that DEI has potential for the diagnosis of cartilage lesions and chondrocalcinosis. PMID- 22674683 TI - Efficient excitation-energy transfer in ion-based organic nanoparticles with versatile tunability of the fluorescence colours. AB - Organic nanoparticles consisting of 3,3'-diethylthiacyanine (TC) and ethidium (ETD) dyes are synthesized by ion-association between the cationic dye mixture (10 % ETD doping) and the tetrakis(4-fluorophenyl)borate (TFPB) anion, in the presence of a neutral stabilizing polymer, in aqueous solution. Doping with ETD makes the particle size smaller than without doping. Size tuning can also be conducted by varying the molar ratio (rho) of the loaded anion to the cationic dyes. The fluorescence spectrum of TC shows good overlap with the absorption of ETD in the 450-600 nm wavelength region, so efficient excitation-energy transfer from TC (donor) to ETD (acceptor) is observed, yielding organic nanoparticles whose fluorescence colours are tunable. Upon ETD doping, the emission colour changes significantly from greenish-blue to reddish or whitish. This change is mainly dependent on rho. For the doped nanoparticle sample with rho=1, the intensity of fluorescence ascribed to ETD is ~150-fold higher than that from pure ETD nanoparticles (efficient antenna effect). Non-radiative Forster resonance energy transfer (FRET) is the dominant mechanism for the ETD fluorescence enhancement. The organic nanoparticles of a binary dye system fabricated by the ion-association method act as efficient light-harvesting antennae, which are capable of transferring light energy to the dopant acceptors in very close proximity to the donors, and can have multi-wavelength emission colours with high fluorescence quantum yields. PMID- 22674684 TI - Regulation of thiamine synthesis in Saccharomyces cerevisiae for improved pyruvate production. AB - Metabolic engineering of Saccharomyces cerevisiae for high-yield production of carboxylic acid requires a cytosolic pyruvate pool as precursor. In this study, a novel strategy to improve pyruvate production and reduce metabolic by-products via regulating thiamine synthesis was explored. Two of the thiamine biosynthesis regulatory genes, THI2 and THI3, were disrupted in the S. cerevisiae parent strain FMME-002. The mutants FMME-002DeltaTHI2 and FMME-002DeltaTHI3 both exhibited an enhanced pyruvate yield. Moreover, FMME-002DeltaTHI2 achieved a relatively higher pyruvate production, and the highest concentration of pyruvate was achieved when 0.04 u m thiamine was added. Enzyme assays and fermentation profiles of the THI2-complemented strain indicated that the observed metabolic changes represented intrinsic effects of THI2 deletion on the physiology of S. cerevisiae. Under optimal C:N ratio conditions, FMME-002DeltaTHI2 produced pyruvate up to 8.21 +/- 0.30 g/l, whereas the ethanol titre decreased to 2.21 +/- 0.24 g/l after 96 h of cultivation. These results demonstrate the possibility of improving pyruvate production by regulating thiamine synthesis in S. cerevisiae. PMID- 22674685 TI - Validation of three coding algorithms to identify patients with end-stage liver disease in an administrative database. AB - PURPOSE: Use of administrative or population-based databases for post-marketing pharmacoepidemiology research in patients with end-stage liver disease (ESLD) has been limited by the difficulty of accurately identifying such patients. Algorithms to identify patients with ESLD using ICD-9-CM codes have not been developed outside of the Veterans Affairs healthcare setting. METHODS: We queried electronic medical records at two tertiary care hospitals to identify patients with ICD-9-CM codes indicative of ESLD. Coding algorithms were developed to identify patients with confirmed ESLD, and these were tested to determine their positive predictive value (PPV). RESULTS: The presence of one inpatient or outpatient ICD-9-CM code for: (i) cirrhosis; (ii) chronic liver disease, and (iii) a hepatic decompensation event yielded a PPV of 85.2% (167/196; 95% CI: 79.4%-89.9%). The PPV increased to 89.3% (150/168; 95% CI: 83.6%-93.5%) when the algorithm required two or more ICD-9-CM codes for a hepatic decompensation. However, an algorithm requiring only one ICD-9-CM code for (i) cirrhosis and (ii) a hepatic decompensation event, in the absence of a chronic liver disease code, yielded a PPV of 85.7% (30/35; 95% CI: 69.7%-95.2%). CONCLUSIONS: A coding algorithm that includes at least one ICD-9-CM code for cirrhosis plus one ICD-9 CM code for a hepatic decompensation event has a high PPV for identifying patients with ESLD. The inclusion of at least two codes indicative of a hepatic decompensation event increased the PPV. This algorithm can be used in future epidemiologic studies to examine the outcomes of a variety of long-term medical therapies in patients with ESLD. Copyright (c) 2012 John Wiley & Sons, Ltd. PMID- 22674686 TI - Language-trained chimpanzees (Pan troglodytes) delay gratification by choosing token exchange over immediate reward consumption. AB - Token exchange inherently introduces an element of delay between behavior and reward and so token studies may help us better understand delay of gratification and self-control. To examine this possibility, we presented three language trained chimpanzees with repeated choices involving different foods that could be eaten immediately or lexigram (graphic symbol) tokens that represented (and could be traded for) foods later. When both options were foods, chimpanzees always chose more preferred foods over less preferred foods. When both options were lexigram tokens representing those same foods, performance remained the same as chimpanzees selected the higher value token and then traded it for food. Then, when faced with choosing a token that could be traded later or choosing a food item that could be eaten immediately, most chimpanzees learned to make whatever response led to the more preferred food. They did this even when that meant selecting a high value lexigram token that could be traded only 2 to 3 min later instead of a medium value, but immediately available, food item. Thus, chimpanzees flexibly selected tokens even though such selections necessarily delayed gratification and required forgoing immediately available food. This finding illustrates the utility of symbolic token exchange for assessing self control in nonhuman animals. PMID- 22674687 TI - Outdated dogma? Busulfan, seizure prophylaxis, and stem cell allografting. PMID- 22674688 TI - Microbial fuel cells and microbial electrochemistry: into the next century! PMID- 22674690 TI - Enzymatic versus microbial bio-catalyzed electrodes in bio-electrochemical systems. AB - Catalyses of electrode reactions by oxidoreductases or living electroactive bacteria are compared and recent advances reviewed. The relation between the biological and nevertheless inert nature of enzymes and the living machinery of electroactive microbes is discussed. The way these biocatalysts may be electrically contacted to anodes or cathodes is considered with a focus on their immobilization at electrodes and on the issue of time stability of these assemblies. Recent improvements in power output of biofuel cells are reviewed together with applications that have appeared in the literature. This account also reviews new approaches for combining enzymes and living microbes in bioelectrochemical systems such as reproducing microbial metabolisms with enzyme cascades and expressing oxidoreductases on genetically engineered microbes. Finally, the use of surface chemistry for studying the microbe-electrode interface and bioelectrodes with cell organelles, such as mitochondria, or with higher organisms, such as yeasts, are discussed. Some perspectives for future research to extend this field are offered as conclusions. PMID- 22674691 TI - Bioelectrochemical systems: an outlook for practical applications. AB - Bioelectrochemical systems (BESs) hold great promise for sustainable production of energy and chemicals. This review addresses the factors that are essential for practical application of BESs. First, we compare benefits (value of products and cleaning of wastewater) with costs (capital and operational costs). Based on this, we analyze the maximum internal resistance (in mOmega m(2) ) and current density that is required to make microbial fuel cells (MFCs) and hydrogen producing microbial electrolysis cells (MECs) cost effective. We compare these maximum resistances to reported internal resistances and current densities with special focus on cathodic resistances. Whereas the current densities of MFCs still need to be increased considerably (i.e., internal resistance needs to be decreased), MECs are closer to application as their current densities can be increased by increasing the applied voltage. For MFCs, the production of high value products in combination with electricity production and wastewater treatment is a promising route. PMID- 22674692 TI - Microbial fuel cells for robotics: energy autonomy through artificial symbiosis. AB - The development of the microbial fuel cell (MFC) technology has seen an enormous growth over the last hundred years since its inception by Potter in 1911. The technology has reached a level of maturity that it is now considered to be a field in its own right with a growing scientific community. The highest level of activity has been recorded over the last decade and it is perhaps considered commonplace that MFCs are primarily suitable for stationary, passive wastewater treatment applications. Sceptics have certainly not considered MFCs as serious contenders in the race for developing renewable energy technologies. Yet this is the only type of alternative system that can convert organic waste-widely distributed around the globe-directly into electricity, and therefore, the only technology that will allow artificial agents to autonomously operate in a plethora of environments. This Minireview describes the history and current state of-the-art regarding MFCs in robotics and their vital role in artificial symbiosis and autonomy. Furthermore, the article demonstrates how pursuing practical robotic applications can provide insights of the core MFC technology in general. PMID- 22674693 TI - A laminar-flow microfluidic device for quantitative analysis of microbial electrochemical activity. AB - We report a laminar flow-based microfluidic bioelectrochemical system (BES) that was fabricated by using polydimethyl siloxane (PDMS) channels and gold electrodes. The microfluidic BES was operated as a potentiostatically controlled two-electrode system. A pure culture of Geobacter sulfurreducens strain PCA, which is a model electrode-respiring bacterium, was grown in the channel and respired with the electrode under strict anaerobic conditions. We took advantage of the short hydraulic retention time (~ 2 min) and response times (<21 min) to rapidly test the effect of certain chemical stimuli, such as O(2) and anthraquinone disulfide (AQDS), on electric current production by G. sulfurreducens. The results showed that: i) short-term (2 min) exposure to O(2) saturated solution did not cause any irreversible toxicity to G. sulfurreducens, and ii) AQDS can be used as a redox mediator by G. sulfurreducens for shuttling electrons between the microbe and the electrode. We, therefore, demonstrate that the microfluidic BES is a promising research tool for gaining insight into microbial electrochemical activity. In our two-dimensional microfluidic-based research tool, a well-defined electrochemical environment can be maintained with the help of laminar flow without a membrane to separate two electrodes. PMID- 22674695 TI - Changes in the sulcal size associated with autism spectrum disorder revealed by sulcal morphometry. AB - Autism spectrum disorder (ASD) is a complex, neurodevelopmental disorder with various structural abnormalities for different patient groups. Because of the heterogeneity of the disorder, several biomarkers have been suggested so far. Here, we explore the potential of sulcal surface and length as biomarkers. Three dimensional T1-weighted images of 15 adolescents of normal intelligence with ASD and 15 age-, sex-, and intelligence quotient-matched control adolescents were analysed using Brainvisa 4.0 (http://www.brainvisa.info), which automatically extracts the cortical folds and labels them as 59 sulcal pieces. For each sulcus, the surface, length, and mean geodesic depth were computed using morphometry analysis within this software package. General linear model was conducted to compare the estimated values for the two groups, ASD and control. In the ASD group, the left insula and the right intraparietal sulcus (IPS) had significantly higher values for surface and length, respectively. Nonetheless for all sulcal pieces, the mean geodesic depth was not significantly different between the two groups. Our results suggest that sulcal surface and length can have correlation with morphological changes of cortex in ASD. Greater surface area and length in insula and IPS, respectively, may reflect greater folding. This could result in greater separation of functions with an impact upon the integrative functions of these regions. PMID- 22674696 TI - Successful use of nitazoxanide in the treatment of recurrent Clostridium difficile infection. AB - A 78-year-old, retired Caucasian male presented in emergency room with 3 days history of progressive watery diarrhoea. Two weeks earlier, he received intravenous levofloxacin for community acquired pneumonia. The patient was diagnosed as severe Clostridium difficile infection based on clinical presentation, labs and imaging studies. The patient was initially treated with intravenous metronidazole and oral vancomycin. While awaiting subacute rehabilitation placement, the patient relapsed twice. After first recurrence the patient was treated with 2 weeks of oral nitazoxanide. After second recurrence, the patient was treated 2 weeks of nitazoxanide followed by tapering dose of vancomycin. The patient was followed and no relapse was reported at 1 year follow up visit. PMID- 22674697 TI - Osteoblastic and fibroblastic multicentric osteosarcoma. AB - Bone sarcomas are uncommon tumours, of which osteosarcoma is the least rare, as well as the third most common malignant tumour in childhood, appearing usually between the 10 and 20 years of age. The case the authors present in this work is of a patient suffering from a long-standing condition encompassing skin and soft tissue lesions. After multiple medical treatments, the patient was diagnosed with squamous osteosarcoma, which required aggressive surgical management and chemotherapy. PMID- 22674698 TI - Occupational cyanide poisoning. AB - Cyanide poisoning has existed for centuries. In most cases, cyanide is combined with other toxic substances; for example with carbon monoxide in fire smoke. Cases of pure cyanide poisoning are rare, and usually due to accidental exposure. Their treatment is based on oxygenation and the infusion of hydroxocobalamin. The seriousness of this type of poisoning calls for a rapid and specific response, which demonstrates the usefulness of non-hospital based medical treatment. The authors report here the case of a man who was the victim of occupational poisoning with sodium cyanide and who was treated at the workplace by fire fighters and the Service Mobile d'Urgence et Reanimation emergency ambulance service. PMID- 22674699 TI - Group-A-streptococcal meningitis in a 7-year-old child--a rare pathogen in a non immune compromised patient. AB - A case is presented of meningitis in a 7-year-old female child caused by Group A streptococcus (GAS), a rare bacterial cause of meningitis, with a high rate of morbidity (46%) and mortality (10%). GAS is susceptible for empiric antibiotic therapy aimed at the most prevalent pathogens of meningitis. As GAS meningitis is typically associated with ear-nose-throat (ENT) infections, specific search for a reservoir is advised. Bacterial typification often demonstrates M-protein gene sequence type (EMM type) 1.0 associated with upper respiratory tract infections and also severe, invasive GAS infections. Follow-up investigation including neurologic developmental status and audiologic testing is necessary. Although GAS is a very uncommon cause of acute bacterial meningitis in children, high morbidity and mortality have been reported. Being associated with ENT infections, a search for a GAS reservoir is proposed. GASs are susceptible for common empiric antibiotic therapies in meningitis. Follow-up investigation is necessary. PMID- 22674700 TI - Osteogenesis imperfecta presenting as aneurysmal subarachnoid haemorrhage in a 53 year-old man. AB - The authors describe a case of aneurysmal subarachnoid haemorrhage in a 53-year old man with background of osteogenesis imperfecta (OI). CT brain revealed diffuse subarachnoid haemorrhage (SAH) and cerebral angiogram subsequently confirmed vertebral artery aneurysm rupture leading to SAH. To the authors knowledge this is the first case of vertebral artery aneurysmal SAH described in OI. A previously undiagnosed OI was confirmed by genetic analysis (COL1A1 gene mutation). This aneurysm was successfully treated by endovascular route. Post interventional treatment patient developed stroke secondary to vasospasm. Communicating hydrocephalus, which developed in the process of management, was successfully treated with ventriculo-peritoneal shunt. The aetio-pathogenesis and management of this condition is described. The authors have reviewed the literature and genetic basis of this disease. PMID- 22674701 TI - Reversal of lifelong mutism after anterior cervical discectomy and fusion for myelopathy. AB - A 34-year-old man with a history of spina bifida occulta, fetal alcohol syndrome and mutism presented with an acute on chronic decline of unsteady gait and right arm and leg weakness over the period of a few months. The patient was non-verbal and communicated using hand gestures. MRI of the cervical spine showed severe stenosis at C4-5 with T2 signal abnormalities. Brain MRI demonstrated mild ventriculomegaly. The patient underwent an anterior cervical discectomy and fusion for severe cervical spine stenosis. Postoperatively the patient's myelopathic symptoms improved. He also became verbal and engaged in conversation. Ten months after surgery, the patient who had previously been non-verbal had developed a vocabulary of more than 50 words. PMID- 22674702 TI - Focal testicular lesions: colour Doppler ultrasound, contrast-enhanced ultrasound and tissue elastography as adjuvants to the diagnosis. AB - The aim of this review is to illustrate the potential of different and newer ultrasound techniques beyond conventional B-mode imaging, including colour Doppler ultrasound, contrast-enhanced ultrasound (CEUS) and tissue elastography, in the characterisation of both benign and malignant intratesticular lesions. Normally, testicular malignancies, either primary or secondary, demonstrate an increase in colour Doppler signal. However, there is a diversity of benign testicular lesions that may mimic testicular malignancies. The use of CEUS improves characterisation of testicular lesions, and confirms lack of vascularity in benign abnormalities such as epidermoid cysts, infarctions, abscesses and changes following trauma. Tissue elastography allows further evaluation of the cellular consistency of the abnormality. Familiarity with the appearances seen with these ultrasound techniques in both benign and malignant abnormalities should aid in improving confidence in arriving at the correct diagnosis. PMID- 22674703 TI - Percutaneous testicular biopsy for indeterminate testicular lesions. AB - Ultrasound forms an important part of the assessment of the testicle. Nevertheless, there are a number of situations in which clinical and radiological assessment is unable to provide a definitive diagnosis of a testicular lump. In these situations, historically, either open biopsy or orchidectomy has been performed. Ultrasound-guided percutaneous testicular biopsy is an alternative, less invasive method of obtaining histological diagnosis. Here we describe the rationale, technique and potential uses of the technique. PMID- 22674704 TI - In vitro and in vivo repeatability of abdominal diffusion-weighted MRI. AB - OBJECTIVE: To study the in vitro and in vivo (abdomen) variability of apparent diffusion coefficient (ADC) measurements at 1.5 T using a free-breathing multislice diffusion-weighted (DW) MRI sequence. METHODS: DW MRI images were obtained using a multislice spin-echo echo-planar imaging sequence with b values=0, 100, 200, 500, 750 and 1000 s mm(-2). A flood-field phantom was imaged at regular intervals over 100 days, and 10 times on the same day on 2 occasions. 10 healthy volunteers were imaged on two separate occasions. Mono-exponential ADC maps were fitted excluding b=0. Paired analysis was carried out on the liver, spleen, kidney and gallbladder using multiple regions of interest (ROIs) and volumes of interest (VOIs). RESULTS: The in vitro coefficient of variation was 1.3% over 100 days, and 0.5% and 1.0% for both the daily experiments. In vivo, there was no statistical difference in the group mean ADC value between visits for any organ. Using ROIs, the coefficient of reproducibility was 20.0% for the kidney, 21.0% for the gallbladder, 24.7% for the liver and 28.0% for the spleen. For VOIs, values fall to 7.7%, 6.4%, 8.6% and 9.6%, respectively. CONCLUSION: Good in vitro repeatability of ADC measurements provided a sound basis for in vivo measurement. In vivo variability is higher and when considering single measurements in the abdomen as a whole, only changes in ADC value greater than 23.1% would be statistically significant using a two-dimensional ROI. This value is substantially lower (7.9%) if large three-dimensional VOIs are considered. PMID- 22674705 TI - Totally implantable venous power ports of the forearm and the chest: initial clinical experience with port devices approved for high-pressure injections. AB - OBJECTIVES: To evaluate the technical success, clinical outcome and safety of percutaneously placed totally implantable venous power ports (TIVPPs) approved for high-pressure injections, and to analyse their value for arterial phase CT scans. METHODS: Retrospectively, we identified 204 patients who underwent TIVPP implantation in the forearm (n=152) or chest (n=52) between November 2009 and May 2011. Implantation via an upper arm (forearm port, FP) or subclavian vein (chest port, CP) was performed under sonographic and fluoroscopic guidance. Complications were evaluated following the standards of the Society of Interventional Radiology. Power injections via TIVPPs were analysed, focusing on adequate functioning and catheter's tip location after injection. Feasibility of automatic bolus triggering, peak injection pressure and arterial phase aortic enhancement were evaluated and compared with 50 patients who had had power injections via classic peripheral cannulas. RESULTS: Technical success was 100%. Procedure-related complications were not observed. Catheter-related thrombosis was diagnosed in 15 of 152 FPs (9.9%, 0.02/100 catheter days) and in 1 of 52 CPs (1.9%, 0.002/100 catheter days) (p<0.05). Infectious complications were diagnosed in 9 of 152 FPs (5.9%, 0.014/100 catheter days) and in 2 of 52 CPs (3.8%, 0.003/100 catheter days) (p>0.05). Arterial bolus triggering succeeded in all attempts; the mean injection pressure was 213.8 psi. Aortic enhancement did not significantly differ between injections via cannulas and TIVPPs (p>0.05). CONCLUSIONS: TIVPPs can be implanted with high technical success rates, and are associated with low rates of complications if implanted with sonographic and fluoroscopic guidance. Power injections via TIVPPs are safe and result in satisfying arterial contrast. Conventional ports should be replaced by TIVPPs. PMID- 22674706 TI - Imaging features of colovesical fistulae on MRI. AB - OBJECTIVES: MRI is routinely used in the investigation of colovesical fistulae at our institute. Several papers have alluded to its usefulness in achieving the diagnosis; however, there is a paucity of literature on its imaging findings. Our objective was to quantify the MRI characteristics of these fistulae. METHODS: We selected all cases over a 4-year period with a final clinical diagnosis of colovesical fistula which had been investigated with MRI. The MRI scans were reviewed in a consensus fashion by two consultant uroradiologists. Their MRI features were quantified. RESULTS: There were 40 cases of colovesical fistulae. On MRI, the fistula morphology consistently fell into three patterns. The most common pattern (71%) demonstrated an intervening abscess between the bowel wall and bladder wall. The second pattern (15%) had a visible track between the affected bowel and bladder. The third pattern (13%) was a complete loss of fat plane between the affected bladder and bowel wall. MRI correctly determined the underlying aetiology in 63% of cases. CONCLUSIONS: MRI is a useful imaging modality in the diagnosis of colovesical fistulae. The fistulae appear to have three characteristic morphological patterns that may aid future diagnoses of colovesical fistulae. To the authors' knowledge, this is the first publication of the MRI findings in colovesical fistulae. PMID- 22674707 TI - A survey of the practice and management of radiotherapy linear accelerator quality control in the UK. AB - OBJECTIVES: The objective of this study was to determine current radiotherapy linear accelerator quality control (QC) practice in the UK, as a comparative benchmark and indicator of development needs, and to raise awareness of QC as a key performance indicator. METHODS: All UK radiotherapy centres were invited to complete an online questionnaire regarding their local QC processes, and submit their QC schedules. The range of QC tests, frequency of measurements and acceptable tolerances in use across the UK were analysed, and consensus and range statistics determined. RESULTS: 72% of the UK's 62 radiotherapy centres completed the questionnaire and 40% provided their QC schedules. 60 separate QC tests were identified from the returned schedules. There was a large variation in the total time devoted to QC between centres: interquartile range from 13 to 26 h per linear accelerator per month. There has been a move from weekly to monthly testing of output calibration in the last decade, with reliance on daily constancy testing equipment. 33% of centres thought their schedules were in need of an update and only 30% used risk-assessment approaches to determine local QC schedule content. Less than 30% of centres regularly complete all planned QC tests each month, although 96% achieve over 80% of tests. CONCLUSIONS: A comprehensive "snapshot" of linear accelerator QC testing practice in the UK has been collated, which demonstrates reasonable agreement between centres in their stated QC test frequencies. However, intelligent design of QC schedules and management is necessary to ensure efficiency and appropriateness. PMID- 22674708 TI - The effect of waiting times from general practitioner referral to MRI or orthopaedic consultation for the knee on patient-based outcomes. AB - OBJECTIVES: The purpose of this study was to test for the effect of waiting time from general practitioner (GP) referral to MRI or to orthopaedic consultation on outcomes of patients with knee problems, and to test whether any characteristics of trial participants predicted waiting time to MRI or orthopaedics. METHODS: We undertook secondary analyses of data on 553 participants from a randomised trial who were recruited from 163 general practices during November 2002 to October 2004. RESULTS: Of the patients allocated to MRI, 263 (94%) had an MRI, and of those referred to orthopaedics, 236 (86%) had an orthopaedic consultation. The median (interquartile range) waiting time in days from randomisation to MRI was 41.0 (21.0-71.0) and to orthopaedic appointment was 78.5 (54.5-167.5). Waiting time was found to have no significant effect on patient outcome for both the Short Form 36-item (SF-36) physical functioning score (p=0.570) and the Knee Quality of Life 26-item (KQoL-26) physical functioning score (p=0.268). There was weak evidence that males waited less time for their MRI (p=0.049) and older patients waited longer for their orthopaedic referral (p=0.049). For patients who resided in the catchment areas of some centres there were significantly longer waiting times for both MRI and orthopaedic appointment. CONCLUSION: Where patients reside is a strong predictor of waiting time for access to services such as MRI or orthopaedics. There is no evidence to suggest, however, that this has a significant effect on physical well-being in the short term for patients with knee problems. PMID- 22674709 TI - Imaging features of bowel toxicities in the setting of molecular targeted therapies in cancer patients. AB - Molecular targeted therapies are becoming ubiquitous in cancer treatment. These drugs may cause gastrointestinal toxicities including perforation, pneumatosis, enteritis, colitis and fistula formation. Knowledge of these complications and their management enables early radiological identification and appropriate intervention, reducing patient morbidity and mortality. PMID- 22674710 TI - Breast tomosynthesis and digital mammography: a comparison of diagnostic accuracy. AB - OBJECTIVE: Our aim was to compare the ability of radiologists to detect breast cancers using one-view breast tomosynthesis (BT) and two-view digital mammography (DM) in an enriched population of diseased patients and benign and/or healthy patients. METHODS: All participants gave informed consent. The BT and DM examinations were performed with about the same average glandular dose to the breast. The study population comprised patients with subtle signs of malignancy seen on DM and/or ultrasonography. Ground truth was established by pathology, needle biopsy and/or by 1-year follow-up by mammography, which retrospectively resulted in 89 diseased breasts (1 breast per patient) with 95 malignant lesions and 96 healthy or benign breasts. Two experienced radiologists, who were not participants in the study, determined the locations of the malignant lesions. Five radiologists, experienced in mammography, interpreted the cases independently in a free-response study. The data were analysed by the receiver operating characteristic (ROC) and jackknife alternative free-response ROC (JAFROC) methods, regarding both readers and cases as random effects. RESULTS: The diagnostic accuracy of BT was significantly better than that of DM (JAFROC: p=0.0031, ROC: p=0.0415). The average sensitivity of BT was higher than that of DM (~90% vs ~79%; 95% confidence interval of difference: 0.036, 0.108) while the average false-positive fraction was not significantly different (95% confidence interval of difference: -0.117, 0.010). CONCLUSION: The diagnostic accuracy of BT was superior to DM in an enriched population. PMID- 22674711 TI - Radiofrequency ablation combined with transcatheter arterial embolisation in rabbit liver: investigation of the ablation zone according to the time interval between the two therapies. AB - OBJECTIVES: This study was designed to evaluate the extent of the radiofrequency ablation zone in relation to the time interval between transcatheter arterial embolisation (TAE) and radiofrequency ablation (RFA) and, ultimately, to determine the optimal strategy of combining these two therapies for hepatocellular carcinoma. METHODS: 15 rabbits were evenly divided into three groups: Group A was treated with RFA alone; Group B was treated with TAE immediately followed by RFA; and Group C was treated with TAE followed by RFA 5 days later. All animals underwent perfusion CT (PCT) scans immediately after RFA. Serum liver transaminases were measured to evaluate acute liver damage. Animals were euthanised for pathological analysis of ablated tissues 10 days after RFA. Non-parametric analyses were conducted to compare PCT indices, the RFA zone and liver transaminase levels among the three experimental groups. RESULTS: Group B showed a significantly larger ablation zone than the other two groups. Arterial liver perfusion and hepatic perfusion index represented well the perfusion decrease after TAE on PCT. Although Group B showed the most elevated liver transaminase levels at 1 day post RFA, the enzymes decreased to levels that were not different from the other groups at 10 days post-RFA. CONCLUSIONS: When combined TAE and RFA therapy is considered, TAE should be followed by RFA as quickly as possible, as it can be performed safely without serious hepatic deterioration, despite the short interval between the two procedures. PMID- 22674712 TI - Ex vivo imaging of mouse brain using micro-CT with non-ionic iodinated contrast agent: a comparison with myelin staining. AB - OBJECTIVE: We investigated the use of micro-CT with contrast agent for the non invasive characterisation of fixed mouse brain tissue specimens as a means to differentiate between grey and white matter. METHODS: Nine mice were divided into two groups for micro-CT (n=6) and myelin staining (n=3) experiments. Six mice underwent in vivo micro-CT and were then prepared for brain specimens by transcardiac perfusion with paraformaldehyde. The six mouse brains were soaked in two different concentrations of non-ionic iodinated contrast agents (60 and 150 mg ml(-1)). Immersion times used for each concentration of iodine were for 3, 7 and 14 days. Three-dimensional ex vivo micro-CT images were acquired with a resolution of 39 MUm(3) to create isotropic images. The other three mice were stained for evaluation of the myelin structure. RESULTS: Soaking the brains in non-ionic iodinated contrast agent resulted in clear differences in signal between the grey matter, the white matter and the ventricular spaces. The 150 mg ml(-1) contrast agent solution yielded images with better contrast-to-noise ratio (CNR) than 60 mg ml(-1) iodine contrast agent solution. 14 days of soaking yielded images with better CNR than 3 and 7 days. The CT contrast of grey and white matter derived from the iodine-soaked fixed brains was strongly related to tissue myelin. CONCLUSION: The present study demonstrated that micro-CT can be used to detect the mouse brain myelin structure at 3, 7 and 14 days after fixation using a CT contrast agent. PMID- 22674713 TI - Ultrasound of the male anterior urethra. AB - Imaging of the anterior male urethra has traditionally been performed by fluoroscopic contrast urethrography. While providing easily interpretable images, this technique has a number of disadvantages associated with it. An alternative approach is to use ultrasound to assess the lumen of the urethra and the periurethral tissues. Here we describe the development of urethral ultrasound and the ascending and descending urethral ultrasound techniques employed in our institution with reference to commonly and uncommonly encountered pathologies. We also identify common pitfalls and how to avoid them. PMID- 22674714 TI - Mechanism of radioprotection by delta-tocotrienol: pharmacokinetics, pharmacodynamics and modulation of signalling pathways. AB - OBJECTIVE: The objective of this study was to investigate the correlation between in vivo delta-tocotrienol (DT3) pharmacokinetics, pharmacodynamics and radiation protection, and to evaluate the effect of DT3 pre-treatment on radiation-induced alterations in apoptotic and autophagic pathways. METHODS: We evaluated pharmacokinetics (plasma, 0.5 to 12 h) and pharmacodynamics (peripheral blood indices; day 3, 7, 10 and 14) after a single subcutaneous injection of 300 mg kg( 1) DT3 in unirradiated CD2F1 mice. Next, we monitored 30-day post-irradiation survival (9.25 Gy) and haematopoietic recovery of DT3-treated mice (7 Gy) exposed to cobalt-60 gamma-irradiation. The effects of DT3 on irradiated bone marrow apoptosis and autophagy were determined by analyses of key caspases (3, 7, 9 and 8), beclin-1 and light chain 3 conversion. RESULTS: Plasma concentration of DT3 reached ~195 uM (Cmax) 1 h after injection (Tmax), and DT3 was eliminated from plasma 12 h later. In unirradiated mice, DT3 significantly increased white blood cells (WBCs), neutrophils, lymphocytes (day 3 post DT3 injection) and platelets (day 7) by 1.5- to 2-fold, over vehicle-treated control. DT3 pre-treatment improved 30-day survival to 100% (~15% in control) and accelerated recovery of reticulocytes, platelets, WBCs, neutrophils, lymphocytes and monocytes in peripheral blood. DT3 reduced activation of caspase-8, caspase-3 and caspase-7, inherent to apoptosis, while increasing autophagy-related beclin-1 expression in irradiated bone marrow. CONCLUSION: These data indicate that DT3 stimulates multilineage haematopoiesis, protects against radiation-induced apoptosis downstream of the mitochondria and stimulates cytoprotective autophagy. Apart from a potent antioxidant activity, DT3 may elicit survival advantage following irradiation by enhancing haematopoiesis and modulating signalling pathways. PMID- 22674715 TI - Experience-dependent expression of NPAS4 regulates plasticity in adult visual cortex. AB - There is evidence that developmental-like plasticity can be reactivated in the adult visual cortex. Although activity-dependent transcription factors underlying the process of plasticity reactivation are currently unknown, recent studies point towards NPAS4 as a candidate gene for the occurrence of plasticity in the adult visual system. Here, we addressed whether NPAS4 is involved in the reinstatement of plasticity by using the monocular deprivation protocol and long term fluoxetine treatment as a pharmacological strategy that restores plasticity in adulthood. A combination of molecular assays for gene expression and epigenetic analysis, gene delivery by lentiviral infection, shRNA interference and electrophysiology as a functional read-out, revealed a previously unknown role for the transcription factor NPAS4 in the regulation of adult visual cortical plasticity. We found that NPAS4 overexpression restores ocular dominance plasticity in adult naive animals whereas NPAS4 down-regulation prevents the plastic outcome caused by fluoxetine in adulthood.Our findings lead the way to the identification of novel therapeutic targets for pathological conditions where reorganization of neuronal networks would be beneficial in adult life. PMID- 22674716 TI - Chronic hypoxia-induced upregulation of Ca2+-activated Cl- channel in pulmonary arterial myocytes: a mechanism contributing to enhanced vasoreactivity. AB - Chronic hypoxic pulmonary hypertension (CHPH) is associated with altered expression and function of cation channels in pulmonary arterial smooth muscle cells (PASMCs), but little is known for anion channels. The Ca(2+)-activated Cl( ) channel (CaCC), recently identified as TMEM16A, plays important roles in pulmonary vascular function. The present study sought to determine the effects of chronic hypoxia (CH) on the expression and function of CaCCs in PASMCs, and their contributions to the vascular hyperreactivity in CHPH. Male Wistar rats were exposed to room air or 10% O(2) for 3-4 weeks to generate CHPH. CaCC current (I(CI.Ca)) elicited by caffeine-induced Ca(2+) release or by depolarization at a constant high [Ca(2+)](i) (500 or 750 nm) was significantly larger in PASMCs of CH rats compared to controls. The enhanced I(CI.Ca)) density in CH PASMCs was unrelated to changes in amplitude of Ca(2+) release, Ca(2+)-dependent activation, voltage-dependent properties or calcineurin-dependent modulation of CaCCs, but was associated with increased TMEM16A mRNA and protein expression. Maximal contraction induced by serotonin, an important mediator of CHPH, was potentiated in endothelium-denuded pulmonary arteries of CH rats. The enhanced contractile response was prevented by the CaCC blockers niflumic acid and T16A(inh)-A01, or by the L-type Ca(2+) channel antagonist nifedipine. The effects of niflumic acid and nifedipine were non-additive. Our results demonstrate for the first time that CH increases I(CI.Ca) density, which is attributable to an upregulation of TMEM16A expression in PASMCs. The augmented CaCC activity in PASMCs may potentiate membrane depolarization and L-type channel activation in response to vasoconstrictors and enhance pulmonary vasoreactivity in CHPH. PMID- 22674717 TI - Consumption of a high-fat diet, but not regular endurance exercise training, regulates hypothalamic lipid accumulation in mice. AB - Obesity is characterised by increased storage of fatty acids in an expanded adipose tissue mass and in peripheral tissues such as the skeletal muscle and liver, where it is associated with the development of insulin resistance. Insulin resistance also develops in the central nervous system with high-fat feeding. The capacity for hypothalamic cells to accumulate/store lipids, and the effects of obesity remain undefined. The aims of this study were (1) to examine hypothalamic lipid content in mice with increased dietary fat intake and in obese ob/ob mice fed a low-fat diet, and (2) to determine whether endurance exercise training could reduce hypothalamic lipid accumulation in high-fat fed mice. Male C57BL/6 mice were fed a low- (LFD) or high-fat diet (HFD) for 12 weeks; ob/ob mice were maintained on a chow diet. HFD-exercise (HFD-ex) mice underwent 12 weeks of high fat feeding with 6 weeks of treadmill exercise training (increasing from 30 to 70 min day(-1)). Hypothalamic lipids were assessed by unbiased mass spectrometry. The HFD increased body mass and hepatic lipid accumulation, and induced glucose intolerance, while the HFD-ex mice had reduced body weight and improved glucose tolerance. A total of 335 lipid molecular species were identified and quantified. Lipids known to induce insulin resistance, including ceramide (22%?), diacylglycerol (25%?), lysophosphatidylcholine (17%?), cholesterol esters (60%?) and dihexosylceramide (33%?), were increased in the hypothalamus of HFD vs. LFD mice. Hypothalamic lipids were unaltered with exercise training and in the ob/ob mice, suggesting that obesity per se does not alter hypothalamic lipids. Overall, hypothalamic lipid accumulation is regulated by dietary lipid content and is refractory to change with endurance exercise training. PMID- 22674718 TI - Morphological, neurochemical and electrophysiological features of parvalbumin expressing cells: a likely source of axo-axonic inputs in the mouse spinal dorsal horn. AB - Perception of normal bodily sensations relies on the precise regulation of sensory information entering the dorsal horn of the spinal cord. Inhibitory, axoaxonic, synapses provide a mechanism for this regulation, but the source of these important inhibitory connections remains to be elucidated. This study shows that a subpopulation of spinal interneurons that expresses parvalbumin and have specific morphological, connectivity and functional characteristics are a likely source of the inhibitory inputs that selectivity regulate non-noxious tactile input in the spinal cord. Our findings suggest that a loss of normal function in parvalbumin positive dorsal horn neurons may result in the development of tactile allodynia, where non-painful stimuli gain the capacity to evoke the sensation of pain. PMID- 22674719 TI - KCa channels and epoxyeicosatrienoic acids: major contributors to thermal hyperaemia in human skin. AB - While it is accepted that NO is responsible for ~60% of the plateau in cutaneous thermal hyperaemia, a large portion of the response remains unknown. We sought to determine whether the remaining ~40% could be attributed to EDHF-mediated activation of KCa channels, and whether the epoxyeicosatrienoic acids (EETs), derived via cytochrome P450, were the predominant EDHF active in the response. Four microdialysis fibres were placed in the forearm skin of 20 subjects. In Protocol 1 (n = 10): (1) Control, (2) N(G)-nitro-l-arginine methyl ester (l NAME), (3) a KCa channel inhibitor, tetraethylammonium (TEA), and (4) TEA + l NAME. In Protocol 2 (n = 10): (1) Control, (2) l-NAME, (3) a cytochrome P450 inhibitor, sulfaphenazole, and (4) sulfaphenazole + l-NAME. Local heating to 42 degrees C was performed and skin blood flow was measured with laser Doppler flowmetry. Data are presented as the percentage of maximal cutaneous vascular conductance (CVC). All drug sites attenuated plateau CVC from the control site (86 +/- 1%) to 79 +/- 3% with sulfaphenazole (P = 0.02 from control), 71 +/- 3% with TEA (P = 0.01 from control), and further to 38 +/- 2% with l-NAME (P < 0.001 from control, P < 0.001 from TEA). Plateau was largely attenuated with sulfaphenazole + l-NAME (24 +/- 2%; P = 0.002 from l-NAME), and nearly abolished with l-NAME + TEA (13 +/- 2%; P = 0.001 from sulfaphenazole + l-NAME), which was not different from baseline (P = 0.14). Furthermore, the initial peak was just 17 +/- 2% with TEA + l-NAME (P < 0.001 from l-NAME). These data suggest EDHFs are responsible for a large portion of initial peak and the remaining 40% of the plateau phase, as administration of TEA in combination with l-NAME abolished the majority of hyperaemia. These data also suggest EETs contribute to about half of the EDHF response. PMID- 22674720 TI - Metabotropic actions of the volatile anaesthetic sevoflurane increase protein kinase M synthesis and induce immediate preconditioning protection of rat hippocampal slices. AB - Anaesthetic preconditioning occurs when a volatile anaesthetic, such as sevoflurane, is administered before a hypoxic or ischaemic insult; this has been shown to improve neuronal recovery after the insult. We found that sevoflurane induced preconditioning in the rat hippocampal slice enhances the hypoxic hyperpolarization of CA1 pyramidal neurons, delays and attenuates their hypoxic depolarization, and increases the number of neurons that recover their resting and action potentials after hypoxia. These altered electrophysiological effects and the improved recovery corresponded with an increase in the amount of a constitutively active, atypical protein kinase C isoform found in brain, protein kinase M zeta (PKMzeta). A selective inhibitor of this kinase, zeta inhibitory peptide (ZIP), blocked the increase in the total amount of PKMzeta protein and the amount of the activated form of this kinase, phospho-PKMzeta (p-PKMzeta); it also blocked the altered electrophysiological effects and the improved recovery. We found that both cycloheximide, a general protein synthesis inhibitor, and rapamycin, a selective inhibitor of the mTOR pathway for regulating protein synthesis, blocked the increase in p-PKMzeta, the electrophysiological changes, and the improved recovery due to sevoflurane-induced preconditioning. Glibenclamide, a KATP channel blocker, when present only during the hypoxia, prevented the enhanced hyperpolarization, the delayed and attenuated hypoxic depolarization, and the improved recovery following sevoflurane-induced preconditioning. To examine the function of persistent PKMzeta and KATP channel activity after the preconditioning was established, we administered 4% sevoflurane for 30 min and then discontinued it for 30 min before 10 min of hypoxia. When either tolbutamide, a KATP channel blocker, or ZIP were administered at least 15 min after the washout of sevoflurane, there was little recovery compared with sevoflurane alone. Thus, continuous KATP channel and PKMzeta activity are required to maintain preconditioning protection. We conclude that sevoflurane induces activation of the mTOR pathway, increasing the new protein synthesis of PKMzeta, which is constitutively phosphorylated to its active form, leading to an increased KATP channel-induced hyperpolarizaton. This hyperpolarization delays and attenuates the hypoxic depolarization, improving the recovery of neurons following hypoxia. Thus, sevoflurane acts via a metabotropic pathway to improve recovery following hypoxia. PMID- 22674721 TI - Physical activity opposes coronary vascular dysfunction induced during high fat feeding in mice. AB - The study's purpose was to investigate if physical activity initiated with the start of high-fat feeding would oppose development of endothelial dysfunction, and if it does, then to determine some potential mechanisms. C57BL/6 female mice were randomly divided into three groups: (1) control low-fat diet (LF-SED; 15% of calories from fat), (2) high-fat diet (HF-SED; 45% of calories from fat), and (3) HF diet given access to a voluntary running wheel (HF-RUN). Our hypothesis was that HF-RUN would differ in multiple markers of endothelial dysfunction from HF SED after 10 weeks of 45%-fat diet, but would not differ from LF-SED. HF-RUN differed from HF-SED in nine determinations in which HF-SED either had decreases in (1) acetylcholine (ACh)-induced and flow-induced vasodilatations in isolated, pressurized coronary arterioles, (2) heart phosphorylated endothelial nitric oxide synthase (p-eNOS/eNOS) protein, (3) coronary arteriole leptin (ob) receptor protein, (4) phosphorylated signal transducer and activator of transcription 3 (p STAT3/STAT3) protein, and (5) coronary arteriole superoxide dismutase 1 protein; or had increases in (6) percentage body fat, (7) serum leptin, (8) coronary arteriole suppressor of cytokine signalling 3 (SOCS3) protein, and (9) coronary arteriole gp91(phox) protein. Higher endothelium-dependent vasodilatation by ACh or leptin was abolished with incubation of NOS inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME) in LF-SED and HF-RUN groups. Further, impaired ACh-induced vasodilatation in HF-SED was normalized by apocynin or TEMPOL to LF-SED and HF RUN. These findings demonstrate multiple mechanisms (eNOS, leptin and redox balance) by which voluntary running opposes the development of impaired coronary arteriolar vasodilatation during simultaneous high-fat feeding. PMID- 22674722 TI - M-type potassium channels modulate Schaffer collateral-CA1 glutamatergic synaptic transmission. AB - Previous studies have suggested that muscarinic receptor activation modulates glutamatergic transmission. M-type potassium channels mediate the effects of muscarinic activation in the hippocampus, and it has been proposed that they modulate glutamatergic synaptic transmission. We tested whether M1 muscarinic receptor activation enhances glutamatergic synaptic transmission via the inhibition of the M-type potassium channels that are present in Schaffer collateral axons and terminals. Miniature excitatory postsynaptic currents (mEPSCs) were recorded from CA1 pyramidal neurons. The M1 receptor agonist, NcN-A 343, increased the frequency of mEPSCs, but did not alter their amplitude. The M channel blocker XE991 and its analogue linopirdine also increased the frequency of mEPSCs. Flupirtine, which opens M-channels, had the opposite effect. XE991 did not enhance mEPSCs frequency in a calcium-free external medium. Blocking P/Q- and N-type calcium channels abolished the effect of XE991 on mEPSCs. These data suggested that the inhibition of M-channels increases presynaptic calcium dependent glutamate release in CA1 pyramidal neurons. The effects of these agents on the membrane potentials of presynaptic CA3 pyramidal neurons were studied using current clamp recordings; activation of M1 receptors and blocking M channels depolarized neurons and increased burst firing. The input resistance of CA3 neurons was increased by the application of McN-A-343 and XE991; these effects were consistent with the closure of M-channels. Muscarinic activation inhibits M-channels in CA3 pyramidal neurons and its efferents - Schaffer collateral, which causes the depolarization, activates voltage-gated calcium channels, and ultimately elevates the intracellular calcium concentration to increase the release of glutamate on CA1 pyramidal neurons. PMID- 22674723 TI - Reticular formation responses to magnetic brain stimulation of primary motor cortex. AB - Transcranial magnetic stimulation (TMS) of cerebral cortex is a popular technique for the non-invasive investigation of motor function. TMS is often assumed to influence spinal circuits solely via the corticospinal tract. We were interested in possible trans-synaptic effects of cortical TMS on the ponto-medullary reticular formation in the brainstem, which is the source of the reticulospinal tract and could also generate spinal motor output. We recorded from 210 single units in the reticular formation of three anaesthetized macaque monkeys whilst TMS was performed over primary motor cortex. Short latency responses were observed consistent with activation of a cortico-reticular pathway. However, we also demonstrated surprisingly powerful responses at longer latency, which often appeared at lower threshold than the earlier effects. These late responses seemed to be generated partly as a consequence of the sound click made by coil discharge, and changed little with coil location. This novel finding has implications for the design of future studies using TMS, as well as suggesting a means of non-invasively probing an otherwise inaccessible important motor centre. PMID- 22674725 TI - Store-operated channels regulate intracellular calcium in mammalian rods. AB - Exposure to daylight closes cyclic nucleotide-gated (CNG) and voltage-operated Ca(2+) -permeable channels in mammalian rods. The consequent lowering of the cytosolic calcium concentration ([Ca(2+)](i)), if protracted, can contribute to light-induced damage and apoptosis in these cells. We here report that mouse rods are protected against prolonged lowering of [Ca(2+)](i) by store-operated Ca(2+) entry (SOCE). Ca(2+) stores were depleted in Ca(2+)-free saline supplemented with the endoplasmic reticulum (ER) sequestration blocker cyclopiazonic acid. Store depletion elicited [Ca(2+)](i) signals that exceeded baseline [Ca(2+)](i) by 5.9 +/- 0.7-fold and were antagonized by an inhibitory cocktail containing 2-APB, SKF 96365 and Gd(3+). Cation influx through SOCE channels was sufficient to elicit a secondary activation of L-type voltage-operated Ca2+ entry. We also found that TRPC1, the type 1 canonical mammalian homologue of the Drosophila photoreceptor TRP channel, is predominantly expressed within the outer nuclear layer of the retina. Rod loss in Pde6b(rdl) (rd1), Chx10/Kip1(-/-rdl) and Elovl4(TG2) dystrophic models was associated with ~70% reduction in Trpc1 mRNA content whereas Trpc1 mRNA levels in rodless cone-full Nrl(-/-) retinas were decreased by ~50%. Genetic ablation of TRPC1 channels, however, had no effect on SOCE, the sensitivity of the rod phototransduction cascade or synaptic transmission at rod and cone synapses. Thus, we localized two new mechanisms, SOCE and TRPC1, to mammalian rods and characterized the contribution of SOCE to Ca(2+) homeostasis. By preventing the cytosolic [Ca(2+)](i) from dropping too low under sustained saturating light conditions, these signalling pathways may protect Ca(2+) dependent mechanisms within the ER and the cytosol without affecting normal rod function. PMID- 22674726 TI - Analysis of factors affecting Ca(2+)-dependent inactivation dynamics of L-type Ca(2+) current of cardiac myocytes in pulmonary vein of rabbit. AB - L-type Ca(2+) channels (ICaLs) are inactivated by an increase in intracellular [Ca(2+)], known as Ca(2+)-dependent inactivation (CDI). CDI is also induced by Ca(2+) released from the sarcoplasmic reticulum (SR), known as release-dependent inhibition (RDI). As both CDI and RDI occur in the junctional subsarcolemmal nanospace (JSS), we investigated which factors are involved within the JSS using isolated cardiac myocytes from the main pulmonary vein of the rabbit. Using the whole-cell patch clamp technique, RDI was readily observed with the application of a pre-pulse followed by a test pulse, during which the ICaLs exhibited a decrease in peak current amplitude and a slower inactivation. A fast acting Ca(2+) chelator, 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), abolished this effect. As the time interval between the pre-pulse and test pulse increased, the ICaLs exhibited greater recovery and the RDI was relieved. Inhibition of the ryanodine receptor (RyR) or the SR Ca(2+)-ATPase (SERCA) greatly attenuated RDI and facilitated ICaL recovery. Removal of extracellular Na(+),which inhibits the Na(+)-Ca(2+) exchange (Incx), greatly enhanced RDI and slowed ICaL recovery, suggesting that Incx critically controls the [Ca(2+)] in the JSS. We incorporated the Ca(2+)-binding kinetics of the ICaL into a previously published computational model. By assuming two Ca(2+)-binding sites in the ICaL, of which one is of low-affinity with fast kinetics and the other is of high-affinity with slower kinetics, the new model was able to successfully reproduce RDI and its regulation by Incx. The model suggests that Incx accelerates Ca(2+) removal from the JSS to downregulate CDI and attenuates SR Ca(2+) refilling. The model may be useful to elucidate complex mechanisms involved in excitation-contraction coupling in myocytes. PMID- 22674727 TI - Posterior brain in fetuses with Dandy-Walker malformation with complete agenesis of the cerebellar vermis at 11-13 weeks: a pilot study. AB - OBJECTIVE: This study aimed to measure the changes in the posterior brain in fetuses with Dandy-Walker malformation (DWM) with complete agenesis of the cerebellar vermis between 11(+0) and 13(+6) weeks of gestation. METHODS: In the midsagittal view, the brain stem (BS) diameter and the brain stem to occipital bone (BSOB) diameter were measured, and the BS/BSOB ratio was calculated in four fetuses with confirmed DWM and 40 normal fetuses. Delta values corrected for CRL were compared between both groups. RESULTS: In contrast to the normal controls, in fetuses with DWM at 11(+0) to 13(+6) weeks of gestation, the border between the fourth ventricle and the cisterna magna was not visible. There were no significant differences in the BS diameter between the two groups (p<0.3). In the DWM group, the mean diameter of the BSOB was found to be significantly higher than in the controls (p=0.0011), and it was above the 95th centile in all four cases. In addition, the BS/BSOB ratio was significantly decreased in fetuses with DWM (p=0.0011). CONCLUSIONS: At 11-13 weeks, fetuses with DWM have measurable abnormalities in the posterior brain. An abnormal appearance of the fourth ventricle-cisterna magna complex was present in all four cases of DWM. PMID- 22674728 TI - Rapid screening and identification of alpha-glucosidase inhibitors from mulberry leaves using enzyme-immobilized magnetic beads coupled with HPLC/MS and NMR. AB - alpha-Glucosidase plays important roles in the digestion and absorption of carbohydrates in the small intestine. The inhibition of alpha-glucosidase is regarded as a potential way to treat diabetes. We established an approach to screening alpha-glucosidase inhibitors from medicinal plants using enzyme-coated magnetic bead. Using 1-(3-dimethyl-aminopropyl)-3-ethylcarbodiimide and N hydroxysuccinimide as reaction reagents, alpha-glucosidase was immobilized on the magnetic beads by covalent linkage. The conjugation of alpha-glucosidase to the magnetic beads was characterized using scanning electron microscope and X-ray diffractometer. The proposed approach was applied in fishing potential alpha glucosidase inhibitors from extract of Morus alba, a Chinese medicinal plant. The structures of potential active compounds were identified via liquid chromatography-mass spectrometry and nuclear magnetic resonance. The results demonstrated that two flavonoids (isoquercitrin and astragalin) could bind to alpha-glucosidase, which was confirmed via conventional alpha-glucosidase inhibitory assay. Our findings suggested that enzyme-coated magnetic beads may be suitable for discovering active compounds from medicinal plants. PMID- 22674730 TI - Electrical stimulation of sacral dermatomes can suppress aberrant urethral reflexes in felines with chronic spinal cord injury. AB - AIMS: Uncoordinated reflex contractions of the external urethral sphincter (EUS) are a major component of voiding dysfunction after neurologic injury. Patterned stimulation of sacral afferent pathways can reduce abnormal EUS reflexes after acute spinal cord injury (SCI); however, effectiveness following chronic SCI is unknown. METHODS: Four adult male cats were implanted with bilateral extradural sacral root electrodes to allow bladder activation and underwent subsequent spinal transection (T10-12). Nine weeks after SCI urethral and bladder pressures were recorded with and without sacral afferent stimulation. Surface electrodes were applied to sacral and lumbar dermatomes and stimulus amplitude set below the muscle fasciculation threshold. The stimulation pattern was varied by on/off times of fixed frequency at each location. RESULTS: Reflexive EUS contractions were observed in all animals after chronic SCI. Patterned sacral dermatome stimulation reduced EUS reflex rate and amplitude in two of four cats. Suppression was dependent on both the stimulus location and pattern. Sacral locations and a stimulation pattern of (0.75 sec on, 0.25 sec off, 20 Hz) were effective in both responder animals. CONCLUSIONS: Patterned sacral dermatome stimulation can reduce abnormal urethral reflexes following chronic SCI. Reflex suppression is dependent on both the stimulation location and stimulus pattern. Reduction of reflexive EUS activity after chronic SCI with this non-destructive and non-invasive approach may provide an advance for the treatment of detrusor sphincter-dyssynergia. PMID- 22674729 TI - The influence of aerobic fitness on cerebral white matter integrity and cognitive function in older adults: results of a one-year exercise intervention. AB - Cerebral white matter (WM) degeneration occurs with increasing age and is associated with declining cognitive function. Research has shown that cardiorespiratory fitness and exercise are effective as protective, even restorative, agents against cognitive and neurobiological impairments in older adults. In this study, we investigated whether the beneficial impact of aerobic fitness would extend to WM integrity in the context of a one-year exercise intervention. Further, we examined the pattern of diffusivity changes to better understand the underlying biological mechanisms. Finally, we assessed whether training-induced changes in WM integrity would be associated with improvements in cognitive performance independent of aerobic fitness gains. Results showed that aerobic fitness training did not affect group-level change in WM integrity, executive function, or short-term memory, but that greater aerobic fitness derived from the walking program was associated with greater change in WM integrity in the frontal and temporal lobes, and greater improvement in short term memory. Increases in WM integrity, however, were not associated with short term memory improvement, independent of fitness improvements. Therefore, while not all findings are consistent with previous research, we provide novel evidence for correlated change in training-induced aerobic fitness, WM integrity, and cognition among healthy older adults. PMID- 22674732 TI - Highly ordered arrays of particle-in-bowl plasmonic nanostructures for surface enhanced raman scattering. AB - A highly ordered particle-in-bowl (PIB) nanostructure array is designed and fabricated to achieve large field enhancement for the surface-enhanced Raman scattering (SERS) application. This new type of PIB structure is composed of an Ag particle located at the bottom of an Au bowl, and the two are separated by a precisely controlled nanoscale dielectric layer. The fabrication of the PIB structure is based on the self-assembly of polystyrene spheres and atomic layer deposition (ALD), which allows good control of the metal particle size and gap distance, as well as large-scale ordering. Numerical simulation reveals a high enhancement of the local field at the nanogaps. The SERS performance of the PIB arrays, and the effects of the Ag particle size and the ALD dielectric layer thickness are characterized, results of which are in reasonable agreement with simulation. With Rhodmaine 6G as the probe molecule, the spatially averaged SERS enhancement factor is on the order of 3.8 * 10(7) and the local field enhancement from simulation can be up to 10(8) . PMID- 22674731 TI - Anti-inflammatory activities of eleven Centaurea species occurring in the Carpathian Basin. AB - Our study aimed at the identification of anti-inflammatory activities of different fractions of C. sadleriana extract after per os administration in rats, the identification of the active compounds of the plant and the investigation of the in vitro anti-inflammatory activities of Centaurea species native to or cultivated in the Carpathian Basin. The aerial parts of Centaurea sadleriana Janka have been used in Hungarian folk medicine to treat the wounds of sheep. Methanol extract of C. sadleriana was fractioned by solvent-solvent partitioning. The n-hexane fraction was further fractionated and the anti-inflammatory activities of certain subfractions were confirmed in vivo in rats. The n-hexane and chloroform fraction of the methanol extract of C. sadleriana exhibited remarkable COX-1 and COX-2 inhibiting effects in vitro. Chromatographic separation of the fractions led to the identification of the active subfractions and 11 compounds (alpha-linolenic acid, gamma-linolenic acid, stigmasterol, beta sitosterol, campesterol, vanillin, pectolinarigenin, salvigenin, hispidulin, chrysoeriol and apigenin). The in vitro screening for anti-inflammatory activities of further Centaurea species occurring in the Carpathian Basin (C. adjarica, C. bracteata, C. cataonica, C. cynaroides, C. dealbata, C. indurata, C. macrocephala, C. melitensis, C. nigrescens, C. ruthenica) revealed considerable COX-1 and COX-2 inhibitory activities. Because C. sadleriana is an endangered species native only to the Carpathian Basin, the investigation of more prevalent species is reasonable. PMID- 22674733 TI - Isolation of a PBP-pincer rhodium complex stabilized by an intermolecular C-H sigma coordination as the fourth ligand. AB - A little help from my friends: a highly reactive, 16-electron square-planar rhodium complex was isolated. This species displays an intermolecular interaction between the rhodium and the C-H bond of another molecule as the fourth ligand to form an infinite network in the crystal lattice. The complex undergoes oxidative addition to the O-H bond of phenol or a primary alkyl alcohol to give the corresponding hydrido-phenoxido Rh(III) complex or carbonyl Rh(I) complex, respectively. PMID- 22674734 TI - How do we get current research into practice? PMID- 22674735 TI - Substrate specificity of fluoroacetate dehalogenase: an insight from crystallographic analysis, fluorescence spectroscopy, and theoretical computations. AB - The high substrate specificity of fluoroacetate dehalogenase was explored by using crystallographic analysis, fluorescence spectroscopy, and theoretical computations. A crystal structure for the Asp104Ala mutant of the enzyme from Burkholderia sp. FA1 complexed with fluoroacetate was determined at 1.2 A resolution. The orientation and conformation of bound fluoroacetate is different from those in the crystal structure of the corresponding Asp110Asn mutant of the enzyme from Rhodopseudomonas palustris CGA009 reported recently (J. Am. Chem. Soc. 2011, 133, 7461). The fluorescence of the tryptophan residues of the wild type and Trp150Phe mutant enzymes from Burkholderia sp. FA1 incubated with fluoroacetate and chloroacetate was measured to gain information on the environment of the tryptophan residues. The environments of the tryptophan residues were found to be different between the fluoroacetate- and chloroacetate bound enzymes; this would come from different binding modes of these two substrates in the active site. Docking simulations and QM/MM optimizations were performed to predict favorable conformations and orientations of the substrates. The F atom of the substrate is oriented toward Arg108 in the most stable enzyme fluoroacetate complex. This is a stable but unreactive conformation, in which the small O-C-F angle is not suitable for the S(N)2 displacement of the F(-) ion. The cleavage of the C-F bond is initiated by the conformational change of the substrate to a near attack conformation (NAC) in the active site. The second lowest energy conformation is appropriate for NAC; the C-O distance and the O-C-F angle are reasonable for the S(N) 2 reaction. The activation energy is greatly reduced in this conformation because of three hydrogen bonds between the leaving F atom and surrounding amino acid residues. Chloroacetate cannot reach the reactive conformation, due to the longer C-Cl bond; this results in an increase of the activation energy despite the weaker C-Cl bond. PMID- 22674736 TI - Resveratrol induces antioxidant defence via transcription factor Yap1p. AB - Resveratrol is a polyphenol suggested to play a protective role against ageing and age-related diseases. We demonstrate that administering low-doses of resveratrol causes ROS accumulation and transcriptional changes in yeast cells and human adipocytes. These changes in gene expression depend on the oxidative transcription factor Yap1p. In particular, resveratrol induces expression of Yap1p gene targets, such as TRX2, TRR1 or AHP1, in a Yap1p-dependent mode. Under resveratrol treatment, Yap1p is phosphorylated and accumulated in the nucleus. Yap1p knockout causes resveratrol sensitivity, which totally depends on the presence of the C-terminal region of Yap1p. Thus, resveratrol may enhance cellular lifespan by hormetic ROS accumulation, which leads to strengthening the cells' antioxidant capacity. PMID- 22674737 TI - Angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers and the risk of developing rheumatoid arthritis in antihypertensive drug users. AB - PURPOSE: Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are effective in the treatment of cardiovascular disease. Next to effects on hypertension and cardiac function, these drugs have anti-inflammatory and immunomodulating properties which may either facilitate or protect against the development of autoimmunity, potentially resulting in autoimmune diseases. Therefore, we determined in the current study the association between ACE inhibitor and ARB use and incident rheumatoid arthritis (RA). METHODS: A matched case-control study was conducted among patients treated with antihypertensive drugs using the Netherlands Information Network of General Practice (LINH) database in 2001-2006. Cases were patients with a first-time diagnosis of RA. Each case was matched to five controls for age, sex, and index date, which was selected 1 year before the first diagnosis of RA. ACE inhibitor and ARB exposure was considered to be any prescription issued in the period before index date. Logistic regression analysis was used to estimate odds ratios (ORs) and their 95% confidence intervals (CI). RESULTS: Our study included 211 cases and 667 matched controls. After controlling for potential confounders, ever use of ACE inhibitors or ARBs was not associated with incident RA (adjusted ORs [95%CI], 0.99 [0.55-1.79] and 1.02 [0.67-1.56], respectively). The adjusted ORs (95%CI) for current and past use of ACE inhibitors were 1.18 (0.75-1.85) and 0.61 (0.28-1.35). For current and past use of ARBs, these adjusted ORs (95%CI) were 1.40 (0.80-2.45) and 0.29 (0.05-1.67), respectively. No duration and dose-effect relationship was observed. CONCLUSIONS: ACE inhibitor or ARB use is not associated with incident RA. PMID- 22674738 TI - Efficient solvent-free hydrogenation of ketones over flame-prepared bimetallic Pt Pd/ZrO(2) catalysts. AB - Named and flamed: Bimetallic Pt-Pd/ZrO(2) catalysts with different Pt/Pd atomic ratios and high dispersion of the metal nanoparticles are prepared by a single step flame-spray pyrolysis. The catalysts show excellent activity and tunable product selectivity for the solvent-free hydrogenation of the ketone model compounds cyclopentanone and acetophenone. PMID- 22674739 TI - Research on bodies of the executed in German anatomy: an accepted method that changed during the Third Reich. Study of anatomical journals from 1924 to 1951. AB - While it is known that bodies of the executed were used for anatomical research in Germany during the Third Reich, it is unclear whether this type of work was unique to the time period or more common in Germany than elsewhere. The dissected persons and the anatomists involved have not been fully investigated. This study of anatomical journals from 1924 to 1951 shows that 166 out of 7,438 [2.2%] German language articles mentioned the use of "material" from the bodies of executed persons. In comparison, only 2 out of 4,702 English language articles explicitly mentioned bodies of the executed. From 1924 to1932, 33 of a total of 3,734 [1%] German articles listed the use of the executed. From 1933 to 1938 the number rose to 46 out of 2,265 [2%], and increased again from 1939 to 1945 to 73 out of 984 [7%]. After the war 15 out of 455 [3%] still dealt with "material" from the executed. German anatomists' familiarity with the use of the executed as a standard for healthy tissues even before 1933 may have contributed to the ease with which they accepted the "opportunities" (large-scale studies and research on women) presented to them by unlimited access to bodies of the executed provided by the abusive National Socialist (NS) legislation and continued using them for some years after the war. German postwar anatomy was built in part on the bodies of NS victims. Information given in some publications will help with further identification of these victims. PMID- 22674740 TI - Prenatal diagnosis and identification of heterozygous frameshift mutation in PRRX1 in an infant with agnathia-otocephaly. PMID- 22674741 TI - The "r" word. PMID- 22674743 TI - Cost-effectiveness of cytochrome P450 2C19 genotype screening for selection of antiplatelet therapy with clopidogrel or prasugrel: a commentary. PMID- 22674744 TI - Bilateral polymicrogyria: always think in chromosome 22q11.2 deletion syndromes. AB - Polymicrogyria (PMG) is a malformation of cortical development due to an abnormal organisation. It is a heterogeneous disorder associated with genetic and acquired events, namely 22q11.2 deletion syndrome also known as DiGeorge syndrome (DGS) /velocardiofacial syndrome (VCFS) among others. This association has been known since 1996 and more than 30 cases have been described. Neurological features include motor and cognitive impairment, epilepsy, microcephaly and spasticity. The authors present an 8-month old infant with minor dysmorphic features, microcephaly, global psychomotor retardation and epilepsy. Brain MRI revealed diffuse bilateral PMG. The 22q11.2 deletion was confirmed by fluorescent in situ hybridisation (FISH). The child had no other manifestation of DGS/VCFS. paediatricians, neuropaediatricians, development specialists and geneticists should be aware that in the presence of PMG, especially when bilateral, 22q11.2 deletion should be investigated, even in the absence of the typical features of DGS/VCFS. On the other hand, in children with 22q11.2 deletion, brain malformations should be ruled out. PMID- 22674745 TI - Working around a contested diagnosis: borderline personality disorder in adolescence. AB - This discourse analytic study sits at the intersection of everyday communications with young people in mental health settings and the enduring sociological critique of diagnoses in psychiatry. The diagnosis of borderline personality disorder (BPD) is both contested and stigmatized, in mental health and general health settings. Its legitimacy is further contested within the specialist adolescent mental health setting. In this setting, clinicians face a quandary regarding the application of adult diagnostic criteria to an adolescent population, aged less than 18 years. This article presents an analysis of interviews undertaken with Child and Adolescent Mental Health Services (CAMHS) clinicians in two publicly funded Australian services, about their use of the BPD diagnosis. In contrast with notions of primacy of diagnosis or of transparency in communications, doctors, nurses and allied health clinicians resisted and subverted a diagnosis of BPD in their work with adolescents. We delineate specific social and discursive strategies that clinicians displayed and reflected on, including: team rules which discouraged diagnostic disclosure; the lexical strategy of hedging when using the diagnosis; the prohibition and utility of informal 'borderline talk' among clinicians; and reframing the diagnosis with young people. For clinicians, these strategies legitimated their scepticism and enabled them to work with diagnostic uncertainty, in a population identified as vulnerable. For adolescent identities, these strategies served to forestall a BPD trajectory, allowing room for troubled adolescents to move and grow. These findings illuminate how the contest surrounding this diagnosis in principle is expressed in everyday clinical practice. PMID- 22674746 TI - Tales of healthy men: male reproductive bodies in biomedicine from 'Lebensborn' to sperm banks. AB - Using the example of 'sperm tales', borne out of the biomedical technologies that went hand in hand with the establishment of the 'science of man' (andrology), the article engages with the epistemic evolution of interrelated biomedical theories and concepts of what constitutes a 'healthy' reproductive male body. The article asks: how has the normative ideal male body been either perpetuated or interrogated through these tales of male reproduction at the interface between scientific and medical technologies? And how were changes to the normalization of male bodies central to clinical practices and cultural understandings of health and illness? With many aspects of the medical history of male reproduction in the 20th century still unexplored, this article will focus on the growing intervention of biomedicine to 'treat' male infertility by way of the classification, standardization and normalization of male corporeality, focusing in particular on the representation and construction of men and the male body, as reflected in medical science and practice from the second half of the 20th century onwards in Germany. The article analyses the rise in importance of sperm in biomedical investigation, including a consideration of the construction of infertility as the defining force behind concepts of 'healthy men', and examines the related conceptualization of male reproductive bodies at the crossroad between 'healthy' and 'normal'. It is argued that the ideal of male reproduction as being inherently healthy has lost ground. By the late 20th century, male bodies have become vulnerable, at least as represented in medical science and technology. PMID- 22674747 TI - Problematizing the neurochemical subject of anti-depressant treatment: the limits of biomedical responses to women's emotional distress. AB - In this article we situate empirical research into women's problematic experiences of anti-depressant medication within broader debates about pharmaceuticalization and the rise of the neurochemical self. We explore how women interpreted and problematized anti-depressant medication as it impeded their recovery in a number of ways. Drawing upon Foucauldian and feminist work we conceptualize anti-depressants as biotechnologies of the self that shaped how women thought about and acted upon their embodied (and hence gendered) subjectivities. Through the interplay of biochemical, emotional and socio cultural effects medication worked to shape women's self-in-recovery in ways that both reinscribed and undermined a neurochemical construction of depression. Our analysis outlines two key discursive constructions that focused on women's problematization of the neurochemical self in response to the side-effects of anti-depressant use. We identified how the failure of medication to alleviate depression contributed to women's reinterpretation of recovery as a process of 'working' on the emotional self. We argue that women's stories act as a form of subjugated knowledge about the material and discursive forces shaping depression and recovery. These findings offer a gendered critique of scientific and market orientated rationalities underpinning neurochemical recovery that obscure the embodied relations of affect and the social conditions that enable the self to change. PMID- 22674748 TI - Medication communication during ward rounds on medical wards: Power relations and spatial practices. AB - Communication plays a crucial role in the management of medications. Ward rounds are sites where health professionals from different disciplines and patients come together to exchange medication information and make treatment decisions. This article examines power relations and spatial practices surrounding medication communication between patients and health professionals including doctors, nurses and pharmacists during ward rounds. Data were collected in two medical wards of a metropolitan teaching hospital in Melbourne, Australia. Data collection methods involved participant observations, field interviews, video-recordings, together with individual and group reflexive interviews. A critical discourse analysis was undertaken to identify the location sites where power relations were reproduced or challenged in ward rounds. Findings demonstrated that traditional medical hierarchies constructed the ways in which doctors communicated about medications during ward rounds. Nurses and pharmacists ventured into the ward round space by using the discourse of preparation and occupying a peripheral physical position. Doctors privileged the discourse of medication rationalization in their ward round discussions, competing with the discourse of inquiry taken up by patients and families. Ward rounds need to be restructured to provide opportunities for nurses and pharmacists to speak at dedicated times and in strategic locations. By critically reflecting upon the complex process of medication communication during ward rounds, greater opportunities exist for enhanced team communication among health professionals. PMID- 22674749 TI - Faux masculinities among college men who experience depression. AB - Depression is a significant problem among college men that can be complicated by masculine ideals of stoicism, reluctance to seek help, and risky self-management strategies. Underpinning these issues are complexities in recognizing what behaviors might be indicative of college men's depressive symptoms. Findings drawn from a qualitative study of 25 Canadian-based college men who self identified or were diagnosed with depression revealed three predominant masculine identities: the angry man; the solitary man; and the risk-reliant man. Within each of these themes men embodied aspects of idealized masculinity that were difficult to distinguish as symptoms of depression or as representative of the activities with which many college men partake. The angry man identity described men who expressed anger, at least in part, to dissipate depression invoked pain and emotional distress. The solitary man category included men who self-isolated, fearing that others would recognize and judge them as harboring depression. Risk reliant men employed strategies including alcohol and other drug overuse rather than relinquish control by engaging with professional health care providers and services. Guided by the overall findings we argue this phenomenon as 'faux masculinities' - characterized by men's engagement in practices consistent with idealized masculine identities but that emerge from and/or in response to the experience of depression. Faux masculinities are discussed within the context of the challenges posed for college men and their health care providers in pointing toward targeted depression interventions. PMID- 22674750 TI - Preclinical pharmacokinetic analysis of armillarisin succinate ester in mouse plasma and tissues by LC-MS/MS. AB - A liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed and validated to determine the concentration of armillarisin succinate ester in mouse plasma and tissues, used for preclinical evaluation. Bavachin was employed as the internal standard. Separation was performed on a 3.5 um Zorbax SB-C(18) column (30 * 2.1 mm), with a mobile phase consisting of methanol and aqueous 20 mm ammonium acetate. Both analyte and internal standard were determined using electrospray ionization and the MS data acquisition was via selected ion monitoring in negative scanning mode. Quantification was performed using the transitions m/z 333 -> 233 and 323 -> 221 for armillarisin succinate ester and internal standard, respectively. The method was validated with respect to linearity, accuracy, precision, recovery and stability. This assay has been successfully applied to a pharmacokinetic and tissue distribution study after intravenous injection of ASE in mouse in a dose of 10 mg/kg. PMID- 22674751 TI - Astragalus membranaceus ameliorates reproductive toxicity induced by cyclophosphamide in male mice. AB - The root of Astragalus membranaceus B(UNGE) (AM) is a medicinal herb that has been capable of reducing the adverse effects of conventional chemotherapy. To investigate the effects of AM on cyclophosphamide (CP)-induced reproductive toxicity in mouse testes, 5-week-old male imprinting control region mice were divided into five groups; CP was treated on the first day of each week for 5 weeks (100 mg/kg, i.p.), and AM was treated for 5 days a week for 5 weeks. At the end of the treatment period, the testes were taken out, cleared of the adhering tissues, and weighed. Epididymis was taken out and used for sperm analysis. Testis samples were frozen for real-time quantitative PCR and Western blot analysis. AM treatment increased diminished relative testes weight, and sperm count and motility in mice treated with CP. CP treatment has detrimental effects on the expression of cAMP-responsive element modulator (CREM), a transcription factor that is highly expressed in male germ cells and is crucial to post-meiotic germ cell differentiation. AM restored CREM at both the mRNA and protein levels. AM has beneficial influences and appears able to ameliorate relative testes weight, sperm parameters, and CREM expression against CP-induced reproductive toxicity. PMID- 22674752 TI - Pulse-coupled chemical oscillators with time delay. AB - Finger on the pulse: in a system of two pulse-coupled Belousov-Zhabotinsky oscillators, introducing a time delay or increasing the coupling strength brings about novel dynamic features (see picture, the two oscillators are shown in different colors), such as reversal of the roles of excitatory and inhibitory coupling or fast anti-phase oscillation. These features are not observed in diffusively coupled systems, and shed light on how such pulse coupling occurs at synapses. PMID- 22674753 TI - Theoretical investigation of the mechanism of primary amines reacting with hexamolybdate: an insight into the organoimido functionalization and related reactions of polyoxometalates. AB - The functionalization of polyoxometalates (POMs), especially with an amino group to yield organonitrogenous derivatives of POMs, is an efficient approach to the enrichment of their structures and the diversification of their properties for various applications. The mechanism for the formation of organonitrogenous derivatized hexamolybdates was explored by investigating the monofunctionalization of the [Mo(6)O(19)](2-) ion with methylamine using the density functional theory (DFT) method. The calculations show that the direct imidoylization of hexamolybdate with methylamine is both kinetically and thermodynamically unfavorable. However, this imidoylization was found to take place readily in the presence of dimethylcarbodiimide (DMC), for which the free energy barrier was calculated to be +32.5 kcal mol(-1) in acetonitrile. Moreover, various factors controlling the efficiency of the imidoylization were examined. The calculations show that [W(5)MoO(19)](2-) has a relatively lower reactivity than [Mo(6)O(19)](2-), and that the imidoylization of [W(6)O(19)](2-) is an unfavorable process. With respect to the effect of carbodiimides, it is found that the catalytic activity is directly proportional to the electron-withdrawing effects of the substituents. As to the reactivity of R-NH(2) , the computation results indicate that the free-energy barriers of the substitution reactions are linearly correlated with the basicity constants (pK(b)) of the amino groups. It is noteworthy that the introduction of the proton dramatically decreases the free energy barrier of the imidoylization of [Mo(6)O(19)](2-) catalyzed by DMC to 24.3 kcal mol(-1) in acetonitrile. PMID- 22674754 TI - Physiological requirements for growth and competitiveness of Dekkera bruxellensis under oxygen-limited or anaerobic conditions. AB - The effect of glucose and oxygen limitation on the growth and fermentation performances of Dekkera bruxellensis was investigated in order to understand which factors favour its propagation in ethanol or wine plants. Although D. bruxellensis has been described as a facultative anaerobe, no growth was observed in mineral medium under complete anaerobiosis while growth was retarded under severe oxygen limitation. In a continuous culture with no gas inflow, glucose was not completely consumed, most probably due to oxygen limitation. When an air/nitrogen mixture (O(2)-content ca. 5%) was sparged to the culture, growth became glucose-limited. In co-cultivations with Saccharomyces cerevisiae, ethanol yields/g consumed sugar were not affected by the co-cultures as compared to the pure cultures. However, different population responses were observed in both systems. In oxygen-limited cultivation, glucose was depleted within 24 h after challenging with S. cerevisiae and both yeast populations were maintained at a stable level. In contrast, the S. cerevisiae population constantly decreased to about 1% of its initial cell number in the sparged glucose-limited fermentation, whereas the D. bruxellensis population remained constant. To identify the requirements of D. bruxellensis for anaerobic growth, the yeast was cultivated in several nitrogen sources and with the addition of amino acids. Yeast extract and most of the supplied amino acids supported anaerobic growth, which points towards a higher nutrient demand for D. bruxellensis compared to S. cerevisiae in anaerobic conditions. PMID- 22674755 TI - A general and efficient heterogeneous gold-catalyzed hydration of nitriles in neat water under mild atmospheric conditions. PMID- 22674756 TI - Synthesis and evaluation of human monoamine oxidase inhibitory activities of some 3,5-diaryl-N-substituted-4,5-dihydro-1H-pyrazole-1-carbothioamide derivatives. AB - Sixteen 3-aryl-5-(4-fluorophenyl)-N-substituted-4,5-dihydro-1H-pyrazole-1 carbothioamide derivatives were synthesized and their structure were identified by UV, IR, (1) H NMR, mass spectra, and microanalyses. The compounds were evaluated in vitro for their human monoamine oxidase (hMAO) inhibitory activities and their MAO-A and -B selectivity. All the compounds were found to potently inhibit MAO-A isoforms. 5-(4-Fluorophenyl)-3-(4-methoxyphenyl)-N-methyl-4,5 dihydro-1H-pyrazole-1-carbothioamide (1.0 * 10(-3) uM) was found to inhibit hMAO A most selectively and potently. The binding mode of 5-(4-fluorophenyl)-3-(4 methoxyphenyl)-N-methyl-4,5-dihydro-1H-pyrazole-1-carbothioamide to hMAO-A was also predicted using docking studies. PMID- 22674757 TI - A retrospective study on the usage of antiepileptic drugs in Asian children from 2000 to 2009 in the largest pediatric hospital in Singapore. AB - PURPOSE: In light of the increasing usage of the newer antiepileptic drugs (AEDs) in other countries, we reviewed the prescribing pattern of AEDs in Singapore over the last 10 years (2000-2009). METHODS: A retrospective review of pharmacy dispensing records solicited from the only children's hospital in Singapore was performed to analyze the trend in AEDs prescribing in the last 10 years. We also examined the correlation between the serum concentrations of valproic acid (VPA), the most-prescribed AED, and seizure control. Descriptive and inferential statistical analyses were then performed on the findings. RESULTS: A total of 41 671 prescriptions on AEDs were retrieved and analyzed. Despite the introduction of the second-generation AEDs, the first generation AEDs still dominate epilepsy treatment in Asian children, with VPA being the mostly prescribed AED (about 40% of the total AEDs usage). The majority of patients (62.8%) were on monotherapy. The mean VPA serum concentration in patients with good seizure control was 68.6 ug/ml (SD = 26.4 ug/ml; range = 12.2-138.0 ug/ml), which was statistically higher than the mean VPA concentration of 57.7 ug/ml (SD = 27.1 ug/ml; range = 11.1 149.0 ug/ml) in patients with poor seizure control (p < 0.0001). CONCLUSION: With VPA being the most prescribed AED in our clinical practice, and the finding in this study that with careful classification of the patients' condition, serum concentrations of VPA generally correlate well with the seizure control, the correct dose titration of VPA with therapeutic drug monitoring is still of paramount importance. PMID- 22674758 TI - The association between overactive bladder and fibromyalgia syndrome: a community survey. AB - AIMS: Fibromyalgia syndrome (FMS) is the most common disease causing chronic generalized pain, and FMS patients often complain of urinary symptoms such as frequency or urgency. This study focuses on the association of overactive bladder (OAB) and FMS in adults aged 40 and over. METHODS: A survey of adults aged 40s and over was conducted in the Guri and Yangpyeong areas of South Korea. The response rate was 74.2% (940/1,266). After excluding subjects with incomplete questionnaires (n = 20), 920 were included in the final analysis. The association of FMS and OAB was analyzed by univariate and multivariate logistic regression analysis. RESULTS: Individuals with FMS had a significantly increased symptoms of OAB after adjustment for gender, age group, and area of residence (odds ratio (OR) 3.39, 95% confidence interval (CI) 1.82-6.31). The association between FMS and severity of OAB was statistical significant (P for trend <0.0001). CONCLUSIONS: OAB is associated with FMS. Moreover FMS increases with severity of OAB. PMID- 22674759 TI - Duodenal window revisited: A histological study using human fetuses. AB - To assess the development of the duodenal window in fetuses, we examined semiserial histological sections of 59 human fetuses with a crown-rump length of 27-156 mm (~4-18 weeks of gestation). In 44 of the 54 fetuses with horizontal sections, the duodenal window was formed by interdigitation of the anterior and posterior muscle slips from the proper duodenal circular muscle coat. The anterior slips approached the common bile duct from the anterior side and wound around the bile duct from the right aspect, whereas the posterior slips approached the main pancreatic duct from the posterior side, reaching the left or outer aspect of the duct without winding. These slips may become longitudinal muscles in the ampulla after birth. Six specimens showed variations in this typical pattern, in that the posterior muscle slips as well as the duodenal longitudinal muscle coat wound around the bile duct. In the remaining four specimens, we observed an abnormal union of the bile and pancreatic ducts, with the duodenal circular muscles suddenly ending along the window or slightly inserted into the right side of the common duct after joining. In all later-stage fetuses, the common sphincter surrounded both the bile and pancreatic ducts in the ampulla. Consequently, at and along the duodenal window, the proper duodenal circular muscle seemed to contribute to fetal sphincter formation. The window was not a simple hiatus but a functional interface between the sphincter and the duodenal wall. PMID- 22674760 TI - The effect of differing pharmacologic strategies on infarct size in primary PCI- more confirmatory data for bivalirudin. PMID- 22674761 TI - How gold is the gold standard? How gold does it need to be? PMID- 22674762 TI - A tale of a bleeding heart. PMID- 22674763 TI - Implicit rationing of percutaneous coronary intervention: the left main test case. PMID- 22674764 TI - The complexities of assessment of the benefit in acute myocardial infarction management. PMID- 22674765 TI - Kinder, gentler PDA devices. PMID- 22674766 TI - Aneurysm of the atrial septum with fenestrations--the crossroads of pathophysiology and intervention. PMID- 22674767 TI - It is more than the size of the tool that matters. PMID- 22674768 TI - Prenatal phenotype of congenital hyperparathyroidism. PMID- 22674769 TI - Simultaneous determination of carisoprodol and aspirin in human plasma using liquid chromatography-tandem mass spectrometry in polarity switch mode: application to a human pharmacokinetic study. AB - A simple, sensitive and rapid LC-MS/MS-ESI method has been developed and validated for simultaneous quantification of the carisoprodol and aspirin in human plasma. Carisoprodol was detected in positive ion mode, whereas aspirin was detected in negative ion mode. Carbamazepine and furosemide were used as internal standards (IS) for quantification of carisoprodol and aspirin, respectively. The extraction procedure involves a liquid-liquid extraction method with ter-butyl methyl ether. Chromatographic separation was achieved on a Zorbax XDB-Phenyl (4.6 * 75 mm, 3.5 um) column using an isocratic mobile phase (5 mm ammonium acetate:methanol, 20:80, v/v) at a flow rate of 0.8 mL/min with a total run time of 2.2 min. A detailed method validation was performed as per the FDA guidelines. The standard curves found to be linear in the range of 25.5-4900 and 15.3-3000 ng/mL for carisoprodol and aspirin, respectively. The results met the acceptance criteria. Carisoprodol and aspirin were found to be stable in various stability studies. The validated method was successfully applied to a pharmacokinetic study following co-administration of carisoprodol (250 mg) and aspirin (75 mg) tablets by oral route to human volunteers. PMID- 22674770 TI - Toxicity of CdTe quantum dots on yeast Saccharomyces cerevisiae. AB - Along with the widespread development of their bioapplications, concerns about the biosafety of quantum dots (QDs) have increasingly attracted intensive attention. This study examines the toxic effect and subcellular location of cadmium telluride (CdTe) QDs with different sizes against yeast Saccharomyces cerevisiae. The innovative approach is based on the combination of microcalorimetric, spectroscopic, electrochemical, and microscopic methods, which allows analysis of the toxic effect of CdTe QDs on S. cerevisiae and its mechanism. According to the values of the half inhibitory concentration (IC(50)), CdTe QDs exhibit marked cytotoxicity in yeast cells at concentrations as low as 80.81 nmol L(-1) for green-emitting CdTe QDs and 17.07 nmol L(-1) for orange emitting CdTe QDs. QD-induced cell death is characterized by cell wall breakage and cytoplasm blebbing. These findings suggest that QDs with sizes ranging from 4.1 to 5.8 nm can be internalized into yeast cells, which then leads to QD induced cytotoxicity. These studies provide valuable information for the design and development of aqueous QDs for biological applications. PMID- 22674771 TI - Integrative self-sorting synthesis of a Fe8Pt6L24 cubic cage. PMID- 22674772 TI - VLDL triglycerides inhibit HDL-associated paraoxonase 1 (PON1) activity: in vitro and in vivo studies. AB - We analyzed, for the first time, both in vitro and in vivo, the effect of very low density lipoprotein (VLDL), or of pure triglycerides, on high-density lipoprotein (HDL)-associated paraoxonase1 (PON1) catalytic activities. Incubation of serum or HDL from healthy subjects with VLDL (0-330 MUg protein/mL) significantly decreased serum PON1 lactonase or arylesterase activities by up to 11% or 24%, and HDL-associated PON1 lactonase or arylesterase activities by up to 32% or 46%, respectively, in a VLDL dose-dependent manner. VLDL (0-660 MUg protein/mL) also inhibited recombinant PON1 (rePON1) lactonase or arylesterase activities by up to 20% or 42%, respectively. Similar inhibitory effect was noted upon rePON1 incubation with pure triglyceride emulsion. Bezafibrate therapy to three hypertriglyceridemic patients (400 mg/day, for one month) significantly decreased serum triglyceride concentration by 67%, and increased serum HDL cholesterol levels by 48%. PON1 arylesterase or paraoxonase activities in the patients' HDL fractions after drug therapy were significantly increased by 86 88%, as compared to PON1 activities before treatment. Similarly, HDL-PON1 protein levels significantly increased after bezafibrate therapy. Finally, bezafibrate therapy improved HDL biological activity, as HDL obtained after drug therapy showed increased ability to induce cholesterol efflux from J774A.1 macrophages, by 19%, as compared to HDL derived before therapy. We thus conclude that VLDL triglycerides inhibit PON1 catalytic activities, and bezafibrate therapy significantly improved HDL-PON1 catalytic and biological activities. PMID- 22674773 TI - Molecular cloning and differential expression of three GnRH genes during ovarian maturation of spotted halibut, Verasper variegatus. AB - In this study, the gonadotropin-releasing hormone (GnRH) genes in spotted halibut were cloned and sequenced by isolating their cDNAs. The species expressed three molecular forms of GnRH in the brain: chicken-type GnRH-II (cGnRH-II), seabream type GnRH (sbGnRH), and salmon-type GnRH (sGnRH). Phylogenetic analysis divided the molecular forms of GnRHs into three branches: cGnRH-II branch, sGnRH branch, and fish-specific GnRH branch. The spatial expression showed that they had the highest expression levels in the brain. cGnRH-II was exclusively detected in the brain, while sbGnRH had a global expression pattern in all examined organs. sGnRH was detected in the brain, pituitary, and ovary. The temporal changes of brain GnRH mRNA expression levels were examined during ovarian maturation and postspawning, and the serum steroid hormones and gonadosomatic index (GSI) were recorded. Amounts of sbGnRH mRNA substantially elevated (P < 0.05) during ovarian maturation, which concomitant with considerable elevation of GSI and serum steroids levels. On the contrary, neither sGnRH nor cGnRH-II mRNA levels showed significant changes during ovarian maturation in this study. These results suggested that these three GnRH genes are the important regulators for the differential expression of GnRH in spotted halibut, and would help us better understand the reproductive endocrine mechanism of spotted halibut. PMID- 22674774 TI - Ligand-based design, synthesis, and pharmacological evaluation of 3 Methoxyquinoxalin-2-carboxamides as structurally novel serotonin type-3 receptor antagonists. AB - Employing a ligand-based approach, 3-methoxyquinoxalin-2-carboxamides were designed as serotonin type-3 (5-HT(3) ) receptor antagonists and synthesized from the starting material o-phenylenediamine in a sequence of reactions. The structures of the synthesized compounds were confirmed by spectral data. These carboxamides were investigated for their 5-HT(3) receptor antagonisms in longitudinal muscle myenteric plexus preparations from guinea-pig ileum against a standard 5-HT(3) agonist, 2-methy-5-HT, and their antagonism activities are expressed as pA(2) values. Compounds 6a (pA(2) : 7.2), 6e (pA(2) : 7.0), 6f (pA(2) : 7.5), 6g (pA(2) : 7.5), 6n (pA(2) : 7.0), and 6o (pA(2) : 7.2) exhibited antagonism greater than that of the standard 5-HT(3) antagonist, ondansetron (pA(2) : 6.9). PMID- 22674775 TI - Stereoselective construction of spiro(butyrolactonepyrrolidines) by highly efficient copper(I)/TF-BiphamPhos-catalyzed asymmetric 1,3-dipolar cycloaddition. AB - Pyrrole into one: The catalytic asymmetric 1,3-dipolar cycloaddition of cyclic aldimino esters has been accomplished for the first time, enabling facile access to spiro(butyrolactonepyrrolidines) containing one spiro quaternary center and three tertiary stereogenic centers (see scheme). The catalytic system performs well with a broad range of substrates, furnishing synthetically useful adducts in high yields, with excellent diastereo- and enantioselectivities under mild conditions. PMID- 22674776 TI - The use of a real-time luciferase assay to quantify gene expression dynamics in the living yeast cell. AB - A destabilized version of firefly luciferase was used in living yeast cells as a real-time reporter for gene expression. This highly sensitive and non-invasive system can be simultaneously used upon many different experimental conditions in small culture aliquots. This allows the dose-response behaviour of gene expression driven by any yeast promoter to be reported and can be used to quantify important parameters, such as the threshold, sensitivity, response time, maximal activity and synthesis rate for a given stimulus. We applied the luciferase assay to the nutrient-regulated GAL1 promoter and the stress responsive GRE2 promoter. We find that luciferase expression driven by the GAL1 promoter responds dynamically to growing galactose concentrations, with increasing synthesis rates determined by the light increment in the initial linear phase of activation. In the case of the GRE2 promoter, we demonstrate that the very short-lived version of luciferase used here is an excellent tool to quantitatively describe transient transcriptional activation. The luciferase expression controlled by the GRE2 promoter responds dynamically to a gradual increase of osmotic or oxidative stress stimuli, which is mainly based on the progressive increase of the time the promoter remains active. Finally, we determined the dose-response behaviour of a single transcription factor binding site in a synthetic promoter context, using the stress response element (STRE) as an example. Taken together, the luciferase assay described here is an attractive tool to rapidly and precisely determine and compare kinetic parameters of gene expression. PMID- 22674777 TI - "Meningitis-retention syndrome": a review. AB - AIMS: A peculiar combination of acute urinary retention and aseptic meningitis has been described. This combination is referred to as meningitis-retention syndrome (MRS), since patients with this syndrome exhibited no other abnormalities, except for mild pyramidal involvement. We aimed to delineate this syndrome by reviewing literatures. METHODS: We performed a systematic review of the literature to identify the frequency, clinical symptoms, urodynamic findings, putrative underlying pathology, and management of this syndrome. RESULTS: Patients with MRS have typical symptoms of fever, headache, stiff neck, and minor pyramidal signs, together with acute urinary retention. The bladder is initially areflexic, but soon becomes either normal or overactive in the repeated urodynamics during the course of the disorder. MRS is thought to be a very mild form of acute disseminated encephalomyelopathy (ADEM), with increased cell count, total protein, and occasional myelin basic protein in the cerebrospinal fluid. Proper management of the acute urinary retention is necessary to avoid bladder injury due to overdistension. The effectiveness of immune treatments (e.g., steroid pulse therapy) in shortening the urinary retention period awaits further study. CONCLUSIONS: Although rare, MRS is a disorder that both urologists and neurologists may encounter. MRS should be listed in the differential diagnosis of acute urinary retention. PMID- 22674778 TI - Completely discrepant results between prenatal QF-PCR rapid aneuploidy testing and cultured cell karyotyping obtained from CVS: lessons from UK audit and re audit of 22,221 cases. PMID- 22674780 TI - Solid-state circular dichroism and hydrogen bonding, part 2: the case of hypothemycin re-investigated. AB - The impact of crystalline forces on the solid-state circular dichroism (CD) spectrum of hypothemycin (), a biologically active molecule extracted from natural sources, has been analyzed by means of time-dependent density functional theory CD calculations. Input structures were extracted from the X-ray geometry of and consisted in the isolated molecule, its cluster with five water molecules, and 20 different dimers (plus water molecules) representative of all the closest neighbors found in the crystal. The effects of solid-state intermolecular hydrogen bonds and through-space exciton couplings in determining the solid-state CD spectrum of hypothemycin were evaluated and compared. PMID- 22674779 TI - Determination of carbamazepine in human urine and serum samples by high performance liquid chromatography with post-column Ru(bipy)2(3+)-Ce(SO4)2 chemiluminescence detection. AB - A novel, sensitive and rapid CL method coupled with high-performance liquid chromatography separation for the determination of carbamazepine is described. The method was based on the fact that carbamazepine could significantly enhance the chemiluminescence of the reaction of cerium sulfate and tris(2,2-bipyridyl) ruthenium(II) in the presence of acid. The chromatographic separation was performed on a Kromasil(r) (Sigma-Aldrich) TM RP-C18 column (id: 150 mm * 4.6 mm, particle size: 5 um, pore size: 100 A) with a mobile phase consisting of methanol water-glacial acetic acid (70:29:1, v/v/v) at a flowrate of 1.0 mL/min, the total analysis time was within 650 s. Under optimal conditions, CL intensity was linear for carbamazepine in the range 2.0 * 10(-8) ~ 4.0 * 10(-5) g/mL, with a detection limit of 6.0 * 10(-9) g/mL (S/N = 3) and the relative standard detection was 2.5% for 2.0 * 10(-6) g/mL (n = 11). This method was successfully applied to the analysis of carbamazepine in human urine and serum samples. The possible mechanism of the CL reaction is also discussed briefly. PMID- 22674781 TI - Epidermal growth factor receptor expression in acute myelogenous leukaemia is associated with clinical prognosis. AB - The epidermal growth factor receptor (EGFR) family belongs to type I receptor tyrosine kinases. Overexpression or mutation of EGFR/ErbB1 gene has been detected in a large number of human solid tumours. According to some previous report, this gene is not expressed in hematological malignancies. However, two recent clinical case reports showed that erlotinib caused complete remission of acute myeloid leukaemia (AML)-M1 in patients who had both AML-M1 and non-small-cell lung cancer. These results are supported by preclinical studies in which EGFR tyrosine kinase inhibitors have anti-proliferative effects on AML. These findings prompted us to determine whether EGFR is expressed in human AML, through a large-scale screening of both leukaemic cell lines and clinical samples. Our results show that EGFR is expressed by about 33% of human AML (containing M1 to M7 subtypes) and by some human leukaemia cell lines (K562, MEG-01, CEM and SKO-007). Its expression is not limited to certain AML types but has been detected in many leukaemic cells. In addition, EGFR expression was intimately associated with the poor clinical outcomes. Finally, we find that only EGFR-positive leukaemic cells respond to antibody-dependent cellular cytotoxicity of cetuximab, the monoclonal antibodies against EGFR. PMID- 22674782 TI - Exploring large weight deletion and the ability to balance confounders when using inverse probability of treatment weighting in the presence of rare treatment decisions. AB - PURPOSE: When medications are modified in response to changing clinical conditions, confounding by indication arises that cannot be controlled using traditional adjustment. Inverse probability of treatment weights (IPTWs) can address this confounding given assumptions of no unmeasured confounders and that all patients have a positive probability of receiving all levels of treatment (positivity). We sought to explore these assumptions empirically in the context of epoetin-alfa (EPO) dosing and mortality. METHODS: We developed a single set of IPTWs for seven EPO dose categories and evaluated achieved covariate balance, mortality hazard ratios, and confidence intervals using two levels of treatment model parameterization and weight deletion. RESULTS: We found that IPTWs improved covariate balance for most confounders, but was not optimal for prior hemoglobin. Including more predictors in the treatment model or retaining highly weighted individuals resulted in estimates closer to the null, although precision decreased. CONCLUSION: We chose to evaluate weights and covariate balance at a single time-point to facilitate an empirical analysis of model assumptions. These same assumptions are applicable to a time-dependent analysis, although empirical examination is not straight forward in that case. We find that the inclusion of rare treatment decisions and the high weights that result is needed for covariate balance under the positivity assumption. Removal of these influential weights can result in bias in either direction relative to the original confounding. It is therefore important to determine the reason for these rare patterns and whether inference is possible for all treatment levels. PMID- 22674783 TI - Rapid LC-MS/MS determination and pharmacokinetic application of linarin in rat plasma. AB - A sensitive, selective and robust liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed for the rapid determination of linarin in rat plasma. Separation of the analyte and warfarin as internal standard (IS) from 100 MUL rat plasma was carried out by simple protein precipitation treatment. Chromatographic separation of the analyte was performed on a Diamonsil(r) C(18) column (150 * 4.6 mm, 5 um) using isocratic mobile phase consisting of methanol 0.5% formic acid (80:20, v/v). The flow rate was 0.6 mL/min and the total run time was not more than 4.0 min. The method was validated over a wide dynamic concentration range of 1.00-1000 ng/mL for linarin. The precision and accuracy values for linarin met the acceptance criteria according to US Food and Drug Administration guidelines. Linarin was stable in the stability studies including a long-term test (-80 degrees C for 43 days), a short-term test (ambient for 2 h and autosampler for 8 h) and three freeze-thaw cycles (-80-25 degrees C). The developed assay method was applied to the pharmacokinetic study in rats after a single intramuscular administration of 713 ug/kg linarin. PMID- 22674784 TI - Fargesin improves lipid and glucose metabolism in 3T3-L1 adipocytes and high-fat diet-induced obese mice. AB - This study examined the effects of fargesin, a neolignan isolated from Magnolia plants, on obesity and insulin resistance and the possible mechanisms involved in these effects in 3T3-L1 adipocytes and high-fat diet (HFD)-induced obese mice. Fargesin promoted the glucose uptake in 3T3-L1 adipocytes. In HFD-induced obese mice, fargesin decreased the body weight gain, white adipose tissue (WAT), and plasma triglyceride, non-esterified fatty acid and glucose levels, and improved the glucose tolerance. Fargesin increased glucose transporter 4 (GLUT4) protein expression and phosphorylation of Akt, AMP-activated protein kinase (AMPK), and acetyl-CoA carboxylase (ACC) in both 3T3-L1 adipocytes and WAT of HFD-induced obese mice. Fargesin also decreased the mRNA expression levels of fatty acid oxidation-related genes, such as peroxisome proliferator-activated receptor alpha (PPARalpha), carnitine palmitoyltransferase-1 (CPT-1), uncoupling protein-2 (UCP 2) and leptin in WAT. Taken together, the present findings suggest that fargesin improves dyslipidemia and hyperglycemia by activating Akt and AMPK in WAT. PMID- 22674785 TI - Re-engineering electrochemical biosensors to narrow or extend their useful dynamic range. PMID- 22674786 TI - TCR-induced T cell activation leads to simultaneous phosphorylation at Y505 and Y394 of p56(lck) residues. AB - Biochemical studies have demonstrated that phosphorylation of lymphocyte cell kinase (p56(lck) ) is crucial for activation of signaling cascades following T cell receptor (TCR) stimulation. However, whether phosphorylation/dephosphorylation of the activating or inhibitory tyrosine residues occurs upon activation is controversial. Recent advances in intracellular staining of phospho-epitopes and cytometric analysis, requiring few cells, have opened up novel avenues for the field of immunological signaling. Here, we assessed p56(lck) phosphorylation, using a multiparameter flow cytometric based detection method following T cell stimulation. Fixation and permeabilization in conjunction with zenon labeling technology and/or fluorescently labeled antibodies against total p56(lck) or cognate phospho tyrosine (pY) residues or surface receptors were used for detection purposes. Our observations showed that activation of Jurkat or primary human T cells using H(2) O(2) or TCR-induced stimulation led to simultaneous phosphorylation of the activating tyrosine residue, Y394 and the inhibitory tyrosine residue, Y505 of p56(lck) . This was followed by downstream calcium flux and expression of T cell activation markers; CD69 and CD40 ligand (CD40L). However, the extent of measurable activation readouts depended on the optimal stimulatory conditions (temperature and/or stimuli combinations). Treatment of cells with a p56(lck) specific inhibitor, PP2, abolished phosphorylation at either residue in a dose dependent manner. Taken together, these observations show that TCR-induced stimulation of T cells led to simultaneous phosphorylation of p56(lck) residues. This implies that dephosphorylation of Y505 is not crucial for p56(lck) activity. Also, it is clear that cytometric analysis provides for a rapid, sensitive, and quantitative method to supplement biochemical studies on p56(lck) signaling pathways in T cells at single cell level. PMID- 22674787 TI - A controllable chiral molecular machine: movement on molecular level. AB - With the view to develop new chiral molecular switches, a new pH-controlled bistable chiral [3]rotaxane with a binaphthalene as chiral moiety is synthesized and characterized. The movement of the macrocycle DB24C8 along the thread tunes the dihedral angle between the two naphthalene rings and supplies tunable circular dichroism output signals. PMID- 22674788 TI - A silver-catalyzed spirocyclization of alkynyl silyl enol ethers. AB - Ring out the old: The cycloisomerization of alkynyl silyl enol ethers proceeds at ambient temperature under the mild conditions of silver catalysis. Mono- or bicyclic spiro compounds can be obtained by 5-exo-dig reactions. Trapping the vinyl silver species with an iodide source, such as N-iodosuccinimide (NIS), afforded the alkenyl iodide derivatives. PMID- 22674789 TI - A new method to efficiently induce a site-specific double-strand break in the fission yeast Schizosaccharomyces pombe. AB - Double-strand DNA breaks are a serious threat to cellular viability and yeast systems have proved invaluable in helping to understand how these potentially toxic lesions are sensed and repaired. An important method to study the processing of DNA breaks in the budding yeast Saccharomyces cerevisiae is to introduce a unique double-strand break into the genome by regulating the expression of the site-specific HO endonuclease with a galactose inducible promoter. Variations of the HO site-specific DSB assay have been adapted to many organisms, but the methodology has seen only limited use in the fission yeast Schizosaccharomyces pombe because of the lack of a promoter capable of inducing endonuclease expression on a relatively short time scale (~1 h). We have overcome this limitation by developing a new assay in which expression of the homing endonuclease I-PpoI is tightly regulated with a tetracycline-inducible promoter. We show that induction of the I-PpoI endonuclease produces rapid cutting of a defined cleavage site (> 80% after 1 h), efficient cell cycle arrest and significant accumulation of the checkpoint protein Crb2 at break-adjacent regions in a manner that is analogous to published findings with DSBs produced by an acute exposure to ionizing irradiation. This assay provides an important new tool for the fission yeast community and, because many aspects of mammalian chromatin organization have been well-conserved in Sz. pombe but not in S. cerevisiae, also offers an attractive system to decipher the role of chromatin structure in modulating the repair of double-stranded DNA breaks. PMID- 22674790 TI - The MIA-QSAR method for the prediction of bioactivities of possible acetylcholinesterase inhibitors. AB - This paper describes the use of the multivariate image analysis-quantitative structure-activity relationship (MIA-QSAR) methodology, which is a method capable of relating chemical structures with their biological activities. This in silico method has been shown to be extremely reliable and provides excellent results, even compared to those obtained by costly and time-consuming methods. Here, a class of acetylcholinesterase inhibitors was studied and three new compounds exhibiting high estimated pIC(50) values were found. They may be promising inhibitors for use in the treatment of Alzheimer's disease. PMID- 22674791 TI - Induction of angiogenesis via topical delivery of basic-fibroblast growth factor from polyvinyl alcohol-dextran blend hydrogel in an ovine model of acute myocardial infarction. AB - Hydrogels are currently used as interesting constructs for the delivery of proteins. In this study, a novel polyvinyl alcohol-dextran (PVA-Dex) blend hydrogel was used for controlled delivery of basic-fibroblast growth factor (bFGF). These biocompatible constructs were sutured to the epicardium as patches on the heart surface to provide slow release of bFGF to the infarcted site in an ovine model of myocardial infarction (MI). Eighteen sheep were randomly divided into three groups (n = 6 each), including group I (control without any patch and bFGF), group II (patch without bFGF) and group III (patch incorporating 100 ug bFGF). They were subjected to coronary artery ligation after lateral thoracotomy, and then in groups II and III the patches were implanted 20-30 min after MI. Cardiac function was assessed by both echocardiography and magnetic resonance imaging (MRI) 2 months after implantation. Then the animals were sacrificed and the hearts subjected to histopathological examination, immunohistochemistry and electron microscopy. Heart lysates were subject to protein expression analysis through western blotting. The results showed that sustained release of bFGF using PVA-Dex blend hydrogel strongly stimulated angiogenesis and increased wall thickness index in the infarcted myocardium. The patch also significantly attenuated the increase in left ventricular end-systolic diameter, but it did not improve cardiac function within 2 months of myocardial infarction. In conclusion, PVA-Dex gel incorporating bFGF can be used as a sustained release construct for therapeutic angiogenesis in ischaemic heart disease. PMID- 22674792 TI - Targeting p90 ribosomal S6 kinase eliminates tumor-initiating cells by inactivating Y-box binding protein-1 in triple-negative breast cancers. AB - Y-box binding protein-1 (YB-1) is the first reported oncogenic transcription factor to induce the tumor-initiating cell (TIC) surface marker CD44 in triple negative breast cancer (TNBC) cells. In order for CD44 to be induced, YB-1 must be phosphorylated at S102 by p90 ribosomal S6 kinase (RSK). We therefore questioned whether RSK might be a tractable molecular target to eliminate TICs. In support of this idea, injection of MDA-MB-231 cells expressing Flag-YB-1 into mice increased tumor growth as well as enhanced CD44 expression. Despite enrichment for TICs, these cells were sensitive to RSK inhibition when treated ex vivo with BI-D1870. Targeting RSK2 with small interfering RNA (siRNA) or small molecule RSK kinase inhibitors (SL0101 and BI-D1870) blocked TNBC monolayer cell growth by ~100%. In a diverse panel of breast tumor cell line models RSK2 siRNA predominantly targeted models of TNBC. RSK2 inhibition decreased CD44 promoter activity, CD44 mRNA, protein expression, and mammosphere formation. CD44(+) cells had higher P-RSK(S221/227) , P-YB-1(S102) , and mitotic activity relative to CD44(-) cells. Importantly, RSK2 inhibition specifically suppressed the growth of TICs and triggered cell death. Moreover, silencing RSK2 delayed tumor initiation in mice. In patients, RSK2 mRNA was associated with poor disease-free survival in a cohort of 244 women with breast cancer that had not received adjuvant treatment, and its expression was highest in the basal-like breast cancer subtype. Taking this further, we report that P-RSK(S221/227) is present in primary TNBCs and correlates with P-YB-1(S102) as well as CD44. In conclusion, RSK2 inhibition provides a novel therapeutic avenue for TNBC and holds the promise of eliminating TICs. PMID- 22674793 TI - Comparison of health-related outcomes for arthritis, chronic joint symptoms, and sporadic joint symptoms: a population-based study. AB - OBJECTIVE: To examine predictors and health outcomes for individuals reporting arthritis, chronic joint symptoms (CJS), or sporadic joint symptoms (SJS) compared to those without arthritis or joint symptoms. METHODS: Data from the 2008 Canadian Community Health Survey (n = 63,134, ages >=15 years) were used for the analyses. Respondents not reporting arthritis as a long-term chronic health condition diagnosed by a health professional were asked about joint symptoms, excluding the back and neck, over the past 12 months and whether these symptoms were present on most days in the past month (CJS) or not (SJS). Log Poisson regression was used to estimate prevalence ratios (PRs) for reporting arthritis, CJS, and SJS, and for reporting health outcomes (physical activity, pain that limits activity, activity limitation, poor/fair self-rated health, and poor/fair self-rated mental health) and health service use (visits to primary care physicians, specialists, physiotherapists, and chiropractors, and overnight hospital stays). RESULTS: Arthritis was reported by 16.0% of the population, CJS by 10.1%, and SJS by 11.6%. Individuals with arthritis were older than those with CJS or SJS. Women reported arthritis and CJS more often. After adjusting for age, sex, socioeconomic status, lifestyle factors, and comorbidities, PRs of all outcomes were higher for the arthritis and CJS groups than the SJS group, with no significant differences in PRs for the arthritis and CJS groups, except for pain that limits activity. CONCLUSION: CJS were reported by 10% of the adult population. Similarities in outcomes to arthritis suggest that CJS have a substantial impact in the population, and that arthritis management advice is likely needed for this group. PMID- 22674794 TI - Dichlorodiphenyltrichloroethane determination in air by thermal desorption gas chromatography-mass spectrometry. AB - BACKGROUND: Current quantitative methods for airborne dichlorodiphenyltrichloroethane (DDT) require collection and extraction times of >= 12 h. The aim of this study was to develop a method for quantifying airborne DDT with a short (<4 h) collection and analysis time. RESULTS: Precision [relative standard deviation (RSD)] for each calibration point (0.8-9.0), linearity (R(2) = 0.99) and apparent recovery (R' = 96.5%) were determined from thermal desorption (TD) gas chromatography-mass spectrometry (GC-MS) analyses of Tenax-TA-packed sampling tubes spiked with 1-250 ng of DDT. Recovery of (13) C labeled 4,4'-DDT from tubes spiked before and after air sampling was 97.3 and 90.3% respectively. DDT was detected and quantified in 1-3 L samples of air collected during 10-180 min sampling events. A significant difference was observed in DDT air concentration between 28 and 33 degrees C during microchamber studies. CONCLUSIONS: The results demonstrate that the TD GC-MS method developed in this study is precise, reproducible and linear over the span of 1-250 ng of DDT spiked onto TD tubes. By avoiding dilution of the sample, the method described allows the measurement of DDT vapor concentrations during short sampling periods (10-180 min) relevant to mosquito behavior studies. PMID- 22674795 TI - Effects of pulsed magnetic field treatment of soybean seeds on calli growth, cell damage, and biochemical changes under salt stress. AB - The effects of magnetic field (MF) treatments of soybean seeds on calli growth, cell damage, and biochemical changes under salt stress were investigated under controlled conditions. Soybean seeds were exposed to a 1.0 Hz sinusoidal uniform pulsed magnetic field (PMF) of 1.5 uT for 5 h/day for 20 days. Non-treated seeds were considered as controls. For callus regeneration, the embryonic axis explants were taken from seeds and inoculated in a saline medium with a concentration of 10 mM NaCl for calli growth analysis and biochemical changes. The combined treatment of MF and salt stress was found to significantly increase calli fresh weight, total soluble sugar, total protein, and total phenol contents, but it decreased the ascorbic acid, lipid peroxidation, and catalase activity of calli from magnetically exposed seeds compared to the control calli. PMF treatment significantly improved calli tolerance to salt stress in terms of an increase in flavonoid, flavone, flavonole, alkaloid, saponin, total polyphenol, genistein, and daidzein contents under salt stress. The results suggest that PMF treatment of soybean seeds has the potential to counteract the adverse effects of salt stress on calli growth by improving primary and secondary metabolites under salt stress conditions. PMID- 22674796 TI - Intracytoplasmic detection of TCL1--but not ILT7-by flow cytometry is useful for blastic plasmacytoid dendritic cell leukemia diagnosis. AB - Diagnosis of blastic plasmacytoid dendritic cell neoplasm (BPDCN) or plasmacytoid dendritic cell leukemia (pDCL) is mainly based on immunophenotypical characterization of leukemic cells in blood or bone marrow samples. We tested by flow cytometry intracellular expression of the proto-oncogene T-cell leukemia 1 (TCL1), as well as membrane and intracellular expression of immunoglobulin-like transcript 7 (ILT7) in 21 pDCL samples and 61 non-pDC acute leukemia samples [i.e., 14 B-acute lymphoblastic leukemia (B-ALL), 9 T-ALL and 38 acute myeloid leukemia (AML)]. TCL1 is highly expressed in all pDCL samples while at a statistically lower level in all B-ALL and 34% of AML. Statistical analysis shows that intensity of TCL1 expression is a good marker for differential diagnosis of pDCL versus other acute leukemia (area under the receiver-operating characteristic curve, [AUC]: 0.96). By contrast, ILT7 positivity is limited to few pDCL samples and cannot be useful for diagnosis purpose. In conclusion, high intracellular intensity of TCL1 expression is currently the best marker for pDC lineage assignment by flow cytometry, which is particularly useful to distinguish pDCL from CD4(+) CD56(+/-) undifferentiated or monoblastic acute leukemia. Thus, intracellular TCL1 detection should be included in acute leukemia diagnosis panels used in hematology laboratories. (c) 2012 International Society for Advancement of Cytometry. PMID- 22674797 TI - The dog as a possible animal model for human non-Hodgkin lymphoma: a review. AB - Lymphoma represents the most frequent hematopoietic cancer in dogs, and it shows significant overlap with the human disease. Several environmental factors have been associated with canine lymphoma, suggesting that they may contribute to lymphomagenesis. Canine lymphoma often presents in advanced stage (III-V) at diagnosis and, most commonly, has an aggressive clinical course requiring prompt treatment, which relies on the use of polychemotherapy. In this review, we will summarize the state-of-the-art of canine lymphoma epidemiology, pathobiology, diagnostic work-up and therapy, and will highlight the links to the corresponding human disease, providing evidence for the use of dog as an animal model of spontaneous disease. PMID- 22674798 TI - Differential effects of polyamine on the cytosolic and mitochondrial NADP isocitrate dehydrogenases. AB - Two isozymes of NADP-dependent isocitrate dehydrogenases (EC 1.1.1.42) exist in mammalian tissues: mitochondrial (ICD1) and cytosolic (ICD2). Effects of polyamines such as spermine, spermidine, and putrescine on the cytosolic and mitochondrial NADP-isocitrate dehydrogenases were analyzed kinetically. Spermine activated ICD2, the cytosolic NADP-isocitrate dehydrogenase from rat liver with the increase in the maximal velocity and the decrease in the affinity for the substrates isocitrate and NADP. The activating action of spermine can be explained by "the uncompetitive effect," and the dissociation constant of spermine for the enzyme-substrate complex was determined to be 1.68 mM. Spermidine and putrescine showed little or no effect. ICD1, the mitochondrial form of NADP-isocitrate dehydrogenase from rat and porcine heart was inhibited by spermine effectively, and by spermidine and putrescine to a lesser extent. Spermine inhibited the enzyme competitively with respect to NADP, and noncompetitively with respect to isocitrate. K(i) value of the enzyme for spermine was 1.3 mM. These results suggest that activation by spermine of cytosolic NADP-isocitrate dehydrogenase can enhance the antioxidant activity by regeneration of GSH, and further is responsible for the stimulation of lipid biosynthesis in cytosol. Spermine may contribute to NADPH supply by enhancing transhydrogenase (EC1.6.1.2) activity through the spermine-dependent activation of Ca(2+) -incorporation to mitochondria. PMID- 22674799 TI - Rhodamine-inspired far-red to near-infrared dyes and their application as fluorescence probes. AB - Probes to dye for: Rhodamine-inspired Si-pyronine, Si-rhodamine, Te-rhodamine, and Changsha NIR dyes have been developed recently. These dyes show fluorescence in the far-red to near-infrared region, while retaining the advantages of the original rhodamines, such as high fluorescence quantum yield, tolerance to photobleaching, good water solubility, and exhibit great potential for biological application. PMID- 22674800 TI - Structural and functional characterization of the interaction of the photosensitizing probe methylene blue with Torpedo californica acetylcholinesterase. AB - The photosensitizer, methylene blue (MB), generates singlet oxygen that irreversibly inhibits Torpedo californica acetylcholinesterase (TcAChE). In the dark, it inhibits reversibly. Binding is accompanied by a bathochromic absorption shift, used to demonstrate displacement by other acetylcholinesterase inhibitors interacting with the catalytic "anionic" subsite (CAS), the peripheral "anionic" subsite (PAS), or bridging them. MB is a noncompetitive inhibitor of TcAChE, competing with reversible inhibitors directed at both "anionic" subsites, but a single site is involved in inhibition. MB also quenches TcAChE's intrinsic fluorescence. It binds to TcAChE covalently inhibited by a small organophosphate (OP), but not an OP containing a bulky pyrene. Differential scanning calorimetry shows an ~8 degrees increase in the denaturation temperature of the MB/TcAChE complex relative to native TcAChE, and a less than twofold increase in cooperativity of the transition. The crystal structure reveals a single MB stacked against Trp279 in the PAS, oriented down the gorge toward the CAS; it is plausible that irreversible inhibition is associated with photooxidation of this residue and others within the active-site gorge. The kinetic and spectroscopic data showing that inhibitors binding at the CAS can impede binding of MB are reconciled by docking studies showing that the conformation adopted by Phe330, midway down the gorge, in the MB/TcAChE crystal structure, precludes simultaneous binding of a second MB at the CAS. Conversely, binding of ligands at the CAS dislodges MB from its preferred locus at the PAS. The data presented demonstrate that TcAChE is a valuable model for understanding the molecular basis of local photooxidative damage. PMID- 22674802 TI - Enantioselective kinetics of alpha-hexachlorocyclohexane in earthworm (Eisenia fedtia) and forest soil. AB - The enantioselective bioaccumulation and elimination behaviors of alpha hexachlorocyclohexane (alpha-HCH) enantiomers in earthworm and soil were investigated by chiral gas chromatography. Enantiomer fraction values were calculated as indicators of the enantioselectivity. The mature earthworms were exposed to 0.10 ug g(-1)(wwt) (0.14 ug g(-1)(dwt)) spiked soil continuously for the bioaccumulation, and the elimination was conducted after an enrichment period in the soil. The results showed that both the bioaccumulation and elimination processes followed monophasic kinetics, body residues of alpha-HCH in earthworm increased to high level at the fifth day, and enantioselectivity was found in the bioaccumulation process with the rate constant (k) of 0.80 d(-1) for (+)-alpha HCH and 0.74 d(-1) for (-)-alpha-HCH. The half life (t(1/2)) of the enantiomers obtained in the elimination process was within one day. The bioaccumulation factors of steady state of alpha-HCH enantiomers were 2.82 for (+)-alpha-HCH and 2.75 for (-)-alpha-HCH. The enantiomer fractions of earthworm and soil obviously below 0.5 during uptake and elimination processes indicate significant enantioselectivity and preferential depuration of (+)-alpha-HCH in earthworm. However, earthworms do not have a great capacity for getting rid of alpha-HCH in polluted soil shown by a contradistinctive experiment. PMID- 22674801 TI - Predictors of recall certainty of dates of analgesic medication use in pregnancy. AB - PURPOSE: Recalled dates of medication use are difficult to validate, particularly for over-the-counter (OTC) medications. We evaluated mothers' recall certainty as an approximation of the accuracy of their recalled exposures. METHODS: We used data from the Slone Epidemiology Center Birth Defects Study collected by retrospective interview of women about pregnancy medication use. For each medication reported, women were asked to report the dates of their use and how certain they were of their reported dates. For this analysis, 32,107 reports from 14,577 analgesic users were categorized as "high" or "low" recall certainty if they considered a reported date as exact or estimated, respectively. Patterns of analgesic use, maternal demographics, and health behaviors were explored as predictors of high recall certainty of dates of analgesic use. We used log binomial regression with the generalized estimating equations extension to account for multiple reports per subject in estimating prevalence ratios (PR) and 95% confidence intervals. RESULTS: Relative to episodes of short-term routine use (>=4 times/week for <=30 days), high recall certainty was more likely for episodes of a single dose (prescription PR = 1.92 (1.61, 2.27); OTC PR = 3.65 (3.03, 4.40)) and less likely for episodes of occasional use (prescription PR = 0.10 (0.05, 0.18); OTC PR = 0.65 (0.53, 0.79)). The association of chronic routine use with high recall certainty was inverse among prescription analgesics and positive among OTC analgesics (prescription PR = 0.56 (0.40, 0.80); OTC PR = 2.46 (1.92, 3.42)). CONCLUSIONS: Some characteristics that were associated with recall accuracy in previous studies were also associated with recall certainty in this study. PMID- 22674803 TI - The kunitz protease inhibitor domain of protease nexin-2 inhibits factor XIa and murine carotid artery and middle cerebral artery thrombosis. AB - Coagulation factor XI (FXI) plays an important part in both venous and arterial thrombosis, rendering FXIa a potential target for the development of antithrombotic therapy. The kunitz protease inhibitor (KPI) domain of protease nexin-2 (PN2) is a potent, highly specific inhibitor of FXIa, suggesting its possible role in the inhibition of FXI-dependent thrombosis in vivo. Therefore, we examined the effect of PN2KPI on thrombosis in the murine carotid artery and the middle cerebral artery. Intravenous administration of PN2KPI prolonged the clotting time of both human and murine plasma, and PN2KPI inhibited FXIa activity in both human and murine plasma in vitro. The intravenous administration of PN2KPI into WT mice dramatically decreased the progress of FeCl(3)-induced thrombus formation in the carotid artery. After a similar initial rate of thrombus formation with and without PN2KPI treatment, the propagation of thrombus formation after 10 minutes and the amount of thrombus formed were significantly decreased in mice treated with PN2KPI injection compared with untreated mice. In the middle cerebral artery occlusion model, the volume and fraction of ischemic brain tissue were significantly decreased in PN2KPI-treated compared with untreated mice. Thus, inhibition of FXIa by PN2KPI is a promising approach to antithrombotic therapy. PMID- 22674804 TI - C-C motif chemokine CCL3 and canonical neutrophil attractants promote neutrophil extravasation through common and distinct mechanisms. AB - Initial observations suggested that C-C motif chemokines exclusively mediate chemotaxis of mononuclear cells. In addition, recent studies also implicated these chemotactic cytokines in the recruitment of neutrophils. The underlying mechanisms remained largely unknown. Using in vivo microscopy on the mouse cremaster muscle, intravascular adherence and subsequent paracellular transmigration of neutrophils elicited by the chemokine (C-C motif) ligand 3 (CCL3, synonym MIP-1alpha) were significantly diminished in mice with a deficiency of the chemokine (C-C motif) receptor 1 (Ccr1(-/-)) or 5 (Ccr5(-/-)). Using cell-transfer techniques, neutrophil responses required leukocyte CCR1 and nonleukocyte CCR5. Furthermore, neutrophil extravasation elicited by CCL3 was almost completely abolished on inhibition of G protein-receptor coupling and PI3Kgamma-dependent signaling, while neutrophil recruitment induced by the canonical neutrophil attractants chemokine (C-X-C motif) ligand 1 (CXCL1, synonym KC) or the lipid mediator platetelet-activating factor (PAF) was only partially reduced. Moreover, Ab blockade of beta(2) integrins, of alpha(4) integrins, or of their putative counter receptors ICAM-1 and VCAM-1 significantly attenuated CCL3 , CXCL1-, or PAF-elicited intravascular adherence and paracellular transmigration of neutrophils. These data indicate that the C-C motif chemokine CCL3 and canonical neutrophil attractants exhibit both common and distinct mechanisms for the regulation of intravascular adherence and transmigration of neutrophils. PMID- 22674805 TI - Revealing the role of phospholipase Cbeta3 in the regulation of VEGF-induced vascular permeability. AB - VEGF induces vascular permeability (VP) in ischemic diseases and cancer, leading to many pathophysiological consequences. The molecular mechanisms by which VEGF acts to induce hyperpermeability are poorly understood and in vivo models that easily facilitate real-time, genetic studies of VP do not exist. In the present study, we report a heat-inducible VEGF transgenic zebrafish (Danio rerio) model through which VP can be monitored in real time. Using this approach with morpholino-mediated gene knock-down and knockout mice, we describe a novel role of phospholipase Cbeta3 as a negative regulator of VEGF-mediated VP by regulating intracellular Ca2+ release. Our results suggest an important effect of PLCbeta3 on VP and provide a new model with which to identify genetic regulators of VP crucial to several disease processes. PMID- 22674808 TI - Evidence of plasmonic coupling in gallium nanoparticles/graphene/SiC. AB - Graphene is emerging as a promising material for plasmonics applications due to its strong light-matter interactions, most of which are theoretically predicted but not yet experimentally realized. Therefore, the integration of plasmonic nanoparticles to create metal nanoparticle/graphene composites enables numerous phenomena important for a range of applications from photonics to catalysis. For these applications it is important to articulate the coupling of photon-based excitations such as the interaction between plasmons in each of the material components, as well as their charge-based interactions dependent upon the energy alignment at the metal/graphene interface. These coupled phenomena underpin an active application area in graphene-based composites due to nanoparticle dependent surface-enhanced Raman scattering (SERS) of graphene phonon modes. This study reveals the coupling of a graphene/SiC support with Ga-nanoparticle localized surface plasmon resonance, which is of particular interest due to its ability to be tuned across the UV into the near-IR region. This work is the first demonstration of the evolving plasmon resonance on graphene during the synthesis of surface-supported metal nanoparticles, thus providing evidence for the theoretically predicted screening revealed by a damped resonance with little energy shift. Therefore, the role of the graphene/substrate heterojunction in tailoring the plasmon resonance for nanoplasmonic applications is shown. Additionally, the coupled phenomena between the graphene-Ga plasmon properties, charge transfer, and SERS of graphene vibrational modes are explored. PMID- 22674807 TI - Second malignancies in total therapy 2 and 3 for newly diagnosed multiple myeloma: influence of thalidomide and lenalidomide during maintenance. AB - Thalidomide and lenalidomide constitute an important part of effective myeloma therapy. Recent data from the Intergroup Francophone du Myelome, Cancer and Leukemia Group B, and Gruppo Italiano Malattie Ematologiche dell Adulto MM-015 trials suggest that lenalidomide maintenance therapy is associated with a higher incidence of second primary malignancies (SPMs), including both hematologic and solid malignancies. In the present study, we analyzed data from the Total Therapy 2 (TT2) trial, along with the 2 Total Therapy 3 (TT3) trials. TT2 patients were assigned randomly to either a control group (no thalidomide) or to the experimental group (thalidomide during induction, between transplantations, and during consolidation and maintenance). The 2 TT3 trials used thalidomide and bortezomib during induction, before and in consolidation after tandem melphalan based transplantation; TT3A applied VTD (bortezomib, thalidomide, dexamethasone) in the first year of maintenance and TD for 2 more years, whereas TT3B used VRD (bortezomib, lenalidomide, dexamethasone) maintenance for 3 years. The cumulative incidence of SPMs did not differ significantly among the TT trial components when measured from enrollment (P = .78) or from initiation of maintenance (P = .82). However, a pairwise comparison of the TT2 arms suggested a lower incidence of hematologic SPMs in the thalidomide maintenance arm (hazard ratio = 0.38; P = .09). These trials are registered at www.clinicaltrials.gov as NCT00573391 (TT2), NCT00081939 (TT3A), and NCT00572169 (TT3B). PMID- 22674806 TI - Mll partial tandem duplication and Flt3 internal tandem duplication in a double knock-in mouse recapitulates features of counterpart human acute myeloid leukemias. AB - The MLL-partial tandem duplication (PTD) associates with high-risk cytogenetically normal acute myeloid leukemia (AML). Concurrent presence of FLT3 internal tandem duplication (ITD) is observed in 25% of patients with MLL-PTD AML. However, mice expressing either Mll-PTD or Flt3-ITD do not develop AML, suggesting that 2 mutations are necessary for the AML phenotype. Thus, we generated a mouse expressing both Mll-PTD and Flt3-ITD. Mll(PTD/WT):Flt3(ITD/WT) mice developed acute leukemia with 100% penetrance, at a median of 49 weeks. As in human MLL-PTD and/or the FLT3-ITD AML, mouse blasts exhibited normal cytogenetics, decreased Mll-WT-to-Mll-PTD ratio, loss of the Flt3-WT allele, and increased total Flt3. Highlighting the adverse impact of FLT3-ITD dosage on patient survival, mice with homozygous Flt3-ITD alleles, Mll(PTD/WT):Flt3(ITD/ITD), demonstrated a nearly 30-week reduction in latency to overt AML. Here we demonstrate, for the first time, that Mll-PTD contributes to leukemogenesis as a gain-of-function mutation and describe a novel murine model closely recapitulating human AML. PMID- 22674810 TI - Study of nanocrystalline BiMnO3-PbTiO3: synthesis, structural elucidation, and magnetic characterization of the whole solid solution. AB - In the last ten years, the study and the search for new multiferroic materials have been a major challenge due to their potential applications in electronic technology. In this way, bismuth-containing perovskites (BiMO(3)), and particularly those in which the metal M position is occupied by a magnetically active cation, have been extensively investigated as possible multiferroic materials. From the point of view of synthesis, only a few of the possible bismuth-containing perovskites can be prepared by conventional methods but at high pressures. Herein, the preparation of one of these potential multiferroic systems, the solid solution xBiMnO(3)-(1-x)PbTiO(3) by mechanosynthesis is reported. Note that this synthetic method allows the oxides with high x values, and more particularly the BiMnO(3) phase, to be obtained as nanocrystalline phases, in a single step and at room temperature without the application of external pressure. These results confirm that, in the case of Bi perovskites, mechanosynthesis is a good alternative to high-pressure synthesis. These materials have been studied from the point of view of their structural characteristics by precession electron diffraction and magnetic property measurements. PMID- 22674809 TI - Pudendal neuromodulation improves voiding efficiency in diabetic rats. AB - AIMS: Diabetic cystopathy is typically manifested as bladder voiding dysfunction, and numerous patients are refractory to standard therapy. In this study, we determined whether electrical stimulation (ES) of the sensory branch of the pudendal nerve could engage an augmenting reflex and thereby improve bladder emptying in a diabetic animal model with cystopathy. METHODS: The efficiency of bladder emptying with ES of the sensory branch of the pudendal nerve at different stimulation intensities was measured in rats at 8 or 18 weeks after the induction of diabetes with streptozotocin. RESULTS: The voiding efficiency (VE) was reduced from 74 +/- 4% to 30 +/- 8% in rats with diabetes for 8 weeks and from 73 +/- 6% to 20 +/- 6% in rats with diabetes for 18 weeks. ES at lower intensities (0.025 0.05 mA) applied to the pudendal sensory nerve did not affect the VE in rats with diabetes for 18 weeks but increased the VE in rats with diabetes for 8 weeks. Subsequently, when the stimulation intensity was elevated to 0.1-0.3 mA, the VEs in rats with diabetes for both 8 and 18 weeks increased to 40-50%. CONCLUSIONS: The results of the present study are consistent with the essential role for pudendal sensory feedback in efficient bladder emptying, and electrical activation of the sensory branch of the pudendal nerve was efficient restoring the voiding function in diabetic animals with cystopathy. This could provide an approach to improve bladder emptying in diabetic patients with voiding dysfunction. PMID- 22674811 TI - Synthesis and anticonvulsant properties of new mannich bases derived from 3,3 disubstituted pyrrolidine-2,5-diones. Part IV. AB - A library of 21 new N-Mannich bases of 3,3-diphenyl- (5a-g), 3-methyl-3-phenyl- (6a-g), and 3-ethyl-3-methylpyrrolidine-2,5-diones (7a-g) were synthesized and evaluated for their anticonvulsant activity in the maximum electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) seizure tests after intraperitoneal injection into mice. The acute neurological toxicity was determined applying the rotarod screen. The results in mice showed that 13 compounds were effective in the MES or/and scPTZ screen. From these, seven molecules were tested in the MES seizures after oral administration in rats. The quantitative studies showed that N-[{4-(2-hydroxyethyl)-piperazin-1-yl}-methyl]-3-methyl-3-phenylpyrrolidine-2,5 dione (6c) and N-[(4-benzylpiperidin-1-yl)-methyl]-3-methyl-3-phenylpyrrolidine 2,5-dione (6f) revealed higher protection in the MES and scPTZ tests than valproic acid or ethosuximide which were used as reference antiepileptic drugs. Four compounds (5c, 6c, 6e, 6f) showed high effectiveness in the 6-Hz psychomotor seizure model of partial and therapy resistant epilepsy. PMID- 22674812 TI - Toxicity of formic acid to red imported fire ants, Solenopsis invicta Buren. AB - BACKGROUND: Ants often compete with other ants for resources. Although formic acid is a common defensive chemical of formicine ants, it does not occur in any other subfamilies in Formicidae. No information on toxicity of formic acid to red imported fire ants, Solenopsis invicta, is available. This study examined its contact and fumigation toxicity to S. invicta in the laboratory. RESULTS: In a contact toxicity bioassay, 24 h LD50 values of formic acid for workers ranged from 124.54 to 197.71 ug ant(-1) . Female alates and queens were much less sensitive to formic acid than workers. At a concentration of 271.72 ug ant(-1) , which killed 81.09 +/- 16.04% of workers, the 24 h mortality was up to 39.64% for female alates and 38.89% for queens. In fumigation bioassays, 24 h LC50 values ranged from 0.26 to 0.50 ug mL(-1) for workers, 0.32 ug mL(-1) for male alates and 0.70 ug mL(-1) for female alates. Complete mortality (100%) in queens occurred 24 h after they had been exposed to 1.57 ug mL(-1) of formic acid. At a concentration of 2.09 ug mL(-1) , KT50 values ranged from 23.03 to 43.85 min for workers, from 37.84 to 58.37 min for male alates, from 86.06 to 121.05 min for female alates and from 68.00 to 85.92 min for queens. CONCLUSION: When applied topically, formic acid was significantly less toxic than bifenthrin to red imported fire ants. Although its fumigation toxicity was lower than that of dichlorvos, formic acid had about an order of magnitude higher toxicity to S. invicta than to other insects studied so far. It may be worth investigating the use of formic acid for managing imported fire ants. PMID- 22674813 TI - Through the looking glass--a new world of proteins enabled by chemical synthesis. AB - 'Chemical ligation'--the regioselective and chemoselective covalent condensation of unprotected peptide segments--has enabled the synthesis of polypeptide chains of more than 200 amino acids. An efficient total chemical synthesis of the insulin molecule has been devised on the basis of a key ester-linked intermediate that is chemically converted to fully active human insulin. Enzyme molecules of defined covalent structure and with full enzymatic activity have been prepared and characterized by high-resolution X-ray crystallography. A 'glycoprotein mimetic' of defined chemical structure and with a mass of 50,825 Da, has been prepared and shown to have full biological activity and improved pharmacokinetic properties. D-protein molecules that are the mirror images of proteins found in the natural world have been prepared by total chemical synthesis. Racemic protein mixtures, consisting of the D-enantiomers and L-enantiomers of a protein molecule, form highly ordered centrosymmetric crystals with great ease; this has enabled the determination of the crystal structures of recalcitrant protein molecules. A protein with a novel linear-loop covalent topology of the peptide chain has been designed and synthesized and its structure determined by facile crystallization as the quasi-racemate with the D-form of the native protein molecule.We have developed an optimized total chemical synthesis of biologically active vascular endothelial growth factor-A; total synthesis of the mirror-image protein will be used to systematically develop D-protein antagonists of this important growth factor. The total chemical synthesis of proteins is now a practical reality and enables access to a new world of protein molecules. PMID- 22674816 TI - Identifying barriers to emergency care services. AB - OBJECTIVE: This paper aims to present a review of published evidence of barriers to emergency care, with attention towards both financial and other barriers. METHOD: With the keywords (financial) accessibility, barriers and emergency care services, citations in PubMed were searched and further selected in the context of the objective of this article. RESULTS: Forty articles, published over a period of 15 years, showed evidence of significant barriers to emergency care. These barriers often tend to persist, despite the fact that the evidence was published many years ago. Several publications stressed the importance of the financial barriers in foregoing or delaying potentially life-saving emergency services, both in poor and rich countries. Other publications report non financial barriers that prevent patients in need of emergency care (pre-hospital and in-patient care) from seeking care, from arriving in the proper emergency department without undue delay or from receiving proper treatment when they do arrive in these departments. CONCLUSION: It is clear that timely access to life saving and disability-preventing emergency care is problematic in many settings. Yet, low-cost measures can likely be taken to significantly reduce these barriers. It is time to make an inventory of these measures and to implement the most cost-effective ones worldwide. PMID- 22674817 TI - Use of a new violet-excitable AmCyan variant as a label in cell analysis. AB - Here we report a new variant of AmCyan fluorescent protein that has been specifically designed for multicolor cell analysis. AmCyan is one of the existing violet fluorochromes for use in flow cytometers equipped with a violet (405 nm) laser. It is also widely used as a label in fluorescent spectroscopy. Limitations on its use are due to the significant AmCyan fluorescence spillover into the FITC detector, due to excitation of AmCyan by the blue (488 nm) laser. In order to resolve this problem, we modified the excitation profile of AmCyan. The new fluorescent protein that we developed, AmCyan100, has an emission profile similar to AmCyan with an emission maximum at 500 nm, but its excitation maximum is shifted to 395 nm, which coincides more closely with the violet laser line and decreases the excitation with the blue laser, thus reducing the spillover observed with the original AmCyan. Moreover, this new protein has a Stokes shift of more than 100 nm compared to the Stokes shift of 31 nm in its precursor. Our data also suggests that AmCyan100-mAb conjugates have brightness similar to AmCyan-mAb conjugates. In summary, AmCyan100 conjugates have minimum spillover into the FITC detector, and can potentially replace existing AmCyan conjugates in multicolor flow cytometry without any changes in instrumental setup and existing reagent panel design. PMID- 22674818 TI - Responsiveness of five outcome measurement instruments in total elbow arthroplasty. AB - OBJECTIVE: To quantify and compare the sensitivity to change of 5 outcome instruments for the elbow joint. METHODS: In a prospective cohort study (n = 65), outcome was measured by the Short Form 36 (SF-36), the Disabilities of the Arm, Shoulder, and Hand questionnaire (DASH), the modified American Shoulder and Elbow Surgeons questionnaire for the elbow, patient part (pmASES) and examiner/clinical part (cmASES), and the Patient-Rated Elbow Evaluation form (PREE). Responsiveness was quantified by the effect size (ES) and standardized response mean (SRM) before and 6 months after total elbow arthroplasty. Receiver operating characteristic (ROC) curves were used to determine the instruments' ability to classify effects into global health change assessment categories. RESULTS: For the total scores, the ES were 1.50 for the PREE, 1.32 for the pmASES, 0.86 for the cmASES, 0.56 for the DASH, and 0.11 for the SF-36 (P <= 0.002 for all differences, except the cmASES and DASH). The same order was found within the subdomains of pain/symptoms and function and remained consistent when using the SRM and in ROC curve analysis. PREE total (area under the ROC curve 0.68), DASH function, and pmASES total and pain (area under the ROC curve range 0.64-0.67) discriminated best between "much better" and the other categories. CONCLUSION: The PREE was the most responsive instrument and can be recommended for every set of measures for elbow joint disorders. The pmASES was slightly less responsive but is a valid alternative. The examiner-assessed cmASES is affected by concerns regarding validity and was relatively less responsive. The DASH for comprehensive measurement of the entire upper extremity and the SF-36 for chronic pain conditions complete the assessment set. PMID- 22674819 TI - Additional genetic abnormalities significantly worsen poor prognosis associated with 1q21 amplification in multiple myeloma patients. AB - We investigated the prognostic value of amp(1q21) alone and in combination with other abnormalities in newly diagnosed myeloma patients. The study group consisted of 104 patients treated with various induction regimens, mostly thalidomide based (87 patients). Amp(1q21) was detected in 49 (47.1%) of patients; in 26 (25.0%) cases, it was combined with del(13q14), in 7 (6.7%) with del(17p13) and in 15 (14.4%) with t(4;14)(p16;q32). The response rate was significantly better in amp(1q21)-negative than in amp(1q21)-positive patients (74.5% vs 55.1%, p = 0.025; complete response 18.2% vs 4.1%, p = 0.024). The median progression-free survival (PFS) was 33.9 months in patients without amp(1q21) and 10.3 months with this aberration (p = 0.002). The presence of additional abnormalities resulted in significantly shortened PFS when compared with patients with isolated amp(1q21): coexisting del(13q14) resulted in 7.8 vs 29.0 months of PFS (p = 0.024) and del(17p13) resulted in 4.0 vs 24.9 months of PFS (p = 0.034). The presence of amp(1q21) significantly influenced overall survival (OS) as well as PFS resulting in the median OS of 26.6 vs 62.4 months (p = 0.018) in patients without amp(1q21). The presence of additional genetic abnormalities significantly affected OS when compared with patients carrying isolated amp(1q21): for del(13q14) 18.9 vs 58.4 months (p = 0.004) and for del(17p13) 12.0 vs 46.5 months (p = 0.036). On multivariate analysis amp(1q21), del(13q14) and del(17p13) were found to be an independent adverse predictors of shorter PFS and OS. Our results showed that the presence of amp(1q21) was associated with poor prognosis. Moreover additional genetic abnormalities made PFS and OS further shortened. PMID- 22674820 TI - Tantalum trabecular metal - addition of human skeletal cells to enhance bone implant interface strength and clinical application. AB - The osteo-regenerative properties of allograft have recently been enhanced by addition of autogenous human bone marrow stromal cells (HBMSCs). Limitations in the use of allograft have prompted the investigation of tantalum trabecular metal (TTM) as a potential alternative. TTM is already in widespread orthopaedic use, although in applications where there is poor initial stability, or when TTM is used in conjunction with bone grafting, initial implant loading may need to be limited. The aim of this study was to evaluate the osteo-regenerative potential of TTM with HBMSCs, in direct comparison to human allograft and autograft. HBMSCs were cultured on blocks of TTM, allograft or autograft in basal and osteogenic media. Molecular profiling, confocal and scanning electron microscopy (SEM) and biochemical assays were used to characterize cell adherence, proliferation and phenotype. Mechanical testing was used to define the tensile characteristics of the constructs. HBMSCs displayed adherence and proliferation throughout TTM, evidenced by immunocytochemistry and SEM, with significant cellular ingrowth and matrix production through TTM. In contrast to cells cultured with allograft, cell proliferation assays showed significantly higher activity with TTM (p < 0.001), although molecular profiling confirmed no significant difference in expression of osteogenic genes. In contrast to acellular constructs, mechanical testing of cell TTM constructs showed enhanced tensile characteristics, which compared favourably to cell-allograft constructs. These studies demonstrated the ability of TTM to support HBMSC growth and osteogenic differentiation comparable to allograft. Thus, TTM represents an alternative to allograft for osteo-regenerative strategies, extending its clinical applications as a substitute for allograft. PMID- 22674821 TI - Assessing the effect of vaccine on spontaneous abortion using time-dependent covariates Cox models. AB - PURPOSE: In studying the safety of vaccine for influenza A (H1N1) given during pregnancy, spontaneous abortion (SAB) is one of the important points to consider. Because women may receive the vaccine any time during their pregnancy, evaluation of the effect of the vaccine on SAB should only take place after vaccination and in the risk window for SAB, that is, the first 20 weeks of gestation. In addition, when such studies are conducted through pregnancy registries where recruitment occurs after pregnancy recognition, the accrued subjects are left truncated in the sense that they are not followed from the start of pregnancy. METHODS: As previously reported, left truncation needs to be properly handled using survival analysis methods to avoid bias. In the context of time-dependent vaccine exposure, a time-dependent covariate Cox model can be used to simultaneously take into account the left truncation and the vaccine exposure timing. RESULTS: In this communication, we illustrate the approach using the Vaccine and Medication in Pregnancy Surveillance System data. We explain in details how the model is fitted using different software. CONCLUSIONS: We recommend survival analysis methods together with collection of necessary data to study the effects of vaccine on SAB. PMID- 22674822 TI - Vitamin D deficiency and depression: causal relationship or artifact? PMID- 22674823 TI - Color tuning in polymer light-emitting diodes with Lewis acids. PMID- 22674824 TI - Circular dichroism spectral data and metadata in the Protein Circular Dichroism Data Bank (PCDDB): a tutorial guide to accession and deposition. AB - The Protein Circular Dichroism Data Bank (PCDDB) is a web-based resource containing circular dichroism (CD) and synchrotron radiation circular dichroism spectral and associated metadata located at http://pcddb.cryst.bbk.ac.uk. This resource provides a freely available, user-friendly means of accessing validated CD spectra and their associated experimental details and metadata, thereby enabling broad usage of this material and new developments across the structural biology, chemistry, and bioinformatics communities. The resource also enables researchers utilizing CD as an experimental technique to have a means of storing their data at a secure site from which it is easily retrievable, thereby making their results publicly accessible, a current requirement of many grant-funding agencies world-wide, as well as meeting the data-sharing requirements for journal publications. This tutorial provides extensive information on searching, accessing, and downloading procedures for those who wish to utilize the data available in the data bank, and detailed information on deposition procedures for creating and validating entries, including comprehensive explanations of their contents and formats, for those who wish to include their data in the data bank. PMID- 22674827 TI - sp2-Iminosugar O-, S-, and N-glycosides as conformational mimics of alpha-linked disaccharides; implications for glycosidase inhibition. AB - The synthesis of mimics of the alpha(1->6)- and alpha(1->4)-linked disaccharides isomaltose and maltose featuring a bicyclic sp(2)-iminosugar nonreducing moiety O , S-, or N-linked to a glucopyranoside residue is reported. The strong generalized anomeric effect operating in sp(2)-iminosugars determines the alpha stereochemical outcome of the glycosylation reactions, independent of the presence or not of participating protecting groups and of the nature of the heteroatom. It also imparts chemical stability to the resulting aminoacetal, aminothioacetal, or gem-diamine functionalities. All the three isomaltose mimics behave as potent and very selective inhibitors of isomaltase and maltase, two alpha-glucosidases that bind the parent disaccharides either as substrate or inhibitor. In contrast, large differences in the inhibitory properties were observed among the maltose mimics, with the O-linked derivative being a more potent inhibitor than the N-linked analogue; the S-linked pseudodisaccharide did not inhibit either of the two target enzymes. A comparative conformational analysis based on NMR and molecular modelling revealed remarkable differences in the flexibility about the glycosidic linkage as a function of the nature of the linking atom in this series. Thus, the N-pseudodisaccharide is more rigid than the O-linked derivative, which exhibits conformational properties very similar to those of the natural maltose. The analogous pseudothiomaltoside is much more flexible than the N- or O-linked derivatives, and can access a broader area of the conformational space, which probably implies a strong entropic penalty upon binding to the enzymes. Together, the present results illustrate the importance of taking conformational aspects into consideration in the design of functional oligosaccharide mimetics. PMID- 22674826 TI - Efficacy of different therapeutic options for spontaneous abdominal abscesses in Crohn's disease: are antibiotics enough? AB - BACKGROUND: Management of abdominal abscesses (AA) in Crohn's disease (CD) always includes antibiotics, and some type of drainage is added according to the response and other considerations. Our aim was to assess the efficacy of different therapeutic approaches to spontaneous AA in CD. METHODS: All cases of AA in CD were identified from the databases of five university hospitals. Postoperative cases were excluded. Therapeutic success was defined as abscess resolution and nonreappearance within 1 year of follow-up. RESULTS: We identified 128 cases in 2236 patients (cumulative incidence 5.7%). Initial therapy included medical therapy with antibiotics alone (42.2%), antibiotics plus percutaneous drainage (23.4%), and antibiotics plus surgical drainage (34.4%). The highest final efficacy corresponded to surgery (91%) as compared with antibiotic therapy alone (63%) or percutaneous drainage (30%). Failure of initial therapy was predicted by immunomodulators at diagnosis (odds ratio [OR] 8.45; 95% confidence interval [CI] 1.16-61.5; P = 0.03), fistula detectable in imaging techniques (OR 5.43; 95% CI 1.18-24.8; P = 0.02), and abscess size (OR 1.65; 95% CI 1.07-2.54; P = 0.02) only for patients treated with antibiotic therapy alone. Percutaneous drainage was associated with 19% of complications (enterocutaneous fistulas 13%); surgery was associated with 13% of postoperative complications (enterocutaneous fistulas 7.7%). Following abscess resolution, 60% of patients were started on thiopurines, 9% on biologics, and in 31% baseline therapy was not modified. CONCLUSIONS: Management of spontaneous AA in CD with antibiotics alone seems to be a good option for small abscesses, especially those without associated fistula and appearing in immunomodulator-naive patients. Surgery offers better results in the remaining clinical settings, although percutaneous drainage can avoid operative treatment in some cases. PMID- 22674828 TI - Effect of spray volume on the deposition, viability and infectivity of entomopathogenic nematodes in a foliar spray on vegetables. AB - BACKGROUND: Spray volume can influence the amount of free water on the leaf surface and subsequently the ability of entomopathogenic nematodes (EPNs) to move. In this study, an investigation was made of the effect of spray volume (548, 730 and 1095 L ha(-1) ) on the deposition, viability and infectivity of EPNs against Galleria mellonella on savoy cabbage, cauliflower and leek. RESULTS: Increasing spray volume decreased nematode deposition on 7.1 cm2 leek leaf discs at a 15 degrees angle with the spray nozzle. Although the number of living nematodes observed on leek after 240 min of exposure was not significantly different between the low-volume application (548 L ha(-1) ) and the high-volume application (1095 L ha(-1) ), a greater infectivity was obtained in the latter application. The higher number of droplets deposited on the leek discs in the high-volume application may have stimulated nematode movement. No significant effect of spray volume was observed on the relative deposition of Steinernema carpocapsae on the bottom side of cauliflower and savoy cabbage leaf discs. In spite of the low S. carpocapsae deposition on the bottom side of the savoy cabbage discs, high infectivity was obtained against G. mellonella. Using the lowest spray volume on savoy cabbage, infectivity decreased with increasing exposure time, while infectivity was not affected by exposure time when a spray volume of 730 L ha(-1) or more was used. CONCLUSION: Spray volume is an important application parameter, as it affects nematode infectivity. Future research should investigate the effect of spray volume in the field and its influence on the effect of adjuvants. PMID- 22674829 TI - New pyrimidinone and fused pyrimidinone derivatives as potential anticancer chemotherapeutics. AB - A series of novel substituted pyrimidinones and fused pyrimidinones (compounds 3 18) were synthesized starting with oxiranylmethanone 2. The in vitro cytotoxicity against a human breast adenocarcinoma (MCF-7) cell line was investigated and most of the tested compounds showed potent cytotoxic activity against the MCF-7 cell line comparable to the activity of the commonly used anticancer drug cisplatin. Treatment of MCF-7 cells with increasing doses (2, 5, 10, and 20 ug/mL) of the tested compounds revealed that the activity of superoxide dismutase and the level of hydrogen peroxide were significantly increased, while the activities of catalase and glutathione peroxidase and the levels of reduced glutathione were significantly lowered compared with control MCF-7 cells. In general, derivatives 11 and 16 revealed the highest anticancer activity among the tested compounds. PMID- 22674830 TI - The provincial health office as performance manager: change in the local healthcare system after Thailand's universal coverage reforms. AB - This paper examines the implementation of Thailand's universal coverage healthcare reforms in a rural province, using data from field studies undertaken in 2003-2005 and 2008-2011. We focus on the strand of policy that aimed to develop primary care by allocating funds to contracting units for primary care (CUPs) responsible for managing local service networks. The two studies document a striking change in the balance of power in the local healthcare system over the 8-year period. Initially, the newly formed CUPs gained influence as 'power followed the money', and the provincial health offices (PHOs), which had commanded the service units, were left with a weaker co-ordination role. However, the situation changed as a new insurance purchaser, the National Health Security Office, took financial control and established regional outposts. National Health Security Office outposts worked with PHOs to develop rationalised management tools-strategic plans, targets, KPIs and benchmarking-that installed the PHOs as performance managers of local healthcare systems. New lines of accountability and changed budgetary systems reduced the power of the CUPs to control resource allocation and patterns of services within CUP networks. Whereas some CUPs fought to retain limited autonomy, the PHO has been able to regain much of its former control. We suggest that implementation theory needs to take a long view to capture the complexity of a major reform initiative and argue for an analysis that recognises the key role of policy networks and advocacy coalitions that span national and local levels and realign over time. PMID- 22674831 TI - Multiparametric assessment of Cd2+ cytotoxicity using MTT-based microfluidic image cytometry. AB - A modified MTT protocol-based microfluidic image cytometry (MUFIC) was performed to assess Cd(2+) induced cytotoxicity. The expanded capabilities of MUFIC, such as in situ measurement, high-throughput, and multiparametric analysis of adherent cells under precisely controlled chemical environments of microfluidic channels, were demonstrated in this study. Multiparametric analysis of MUFIC data has enabled us to categorize the progress of cell death into at least four different subgroups based on their morphology and metabolic activity. These advantages of the MTT-based MUFIC as a simpler, cheaper, and faster in vitro cell-based assay tool have many implications in biomedical, pharmaceutical, toxicological, and biological application areas, and we propose this technique as a future high throughput-high content screening (HT-HCS) platform for cytotoxicity assays and drug screening. PMID- 22674832 TI - Association of weight gain with incident knee pain, stiffness, and functional difficulties: a longitudinal study. AB - OBJECTIVE: To examine the longitudinal association between significant weight change and change in knee symptoms (pain, stiffness, and function), and to determine whether the effects differ in those who are obese and those with osteoarthritis (OA). METHODS: Two hundred fifty subjects ranging from normal weight to obese (body mass index range 16.9-59.1 kg/m(2) ) and no significant musculoskeletal disease were recruited from the general community and weight loss clinics and organizations. Seventy-eight percent were followed at ~2 years. Weight, height, and knee symptoms (using the Western Ontario and McMaster Universities Osteoarthritis Index) were assessed at baseline and followup. Any weight loss methods were recorded. RESULTS: Thirty percent of subjects lost >=5% of baseline weight, 56% of subjects' weight remained stable (loss or gain of <5% of baseline weight), and 14% of subjects gained >=5% of baseline weight. Using estimated marginal means, weight gain was associated with worsening pain (mean 27.1 mm; 95% confidence interval [95% CI] -1.1, 55.2), stiffness (mean 18.4 mm; 95% CI 1.5, 35.3), and function (mean 99.3 mm; 95% CI 4.0, 194.6) compared to stable weight. Weight loss was associated with reduced pain (mean -22.4 mm; 95% CI -44.4, -0.3), stiffness (mean -15.3 mm; 95% CI -28.50, -2.0), and function (mean -73.2 mm; 95% CI -147.9, 1.3) compared to stable weight. CONCLUSION: Weight gain was associated with adverse effects on knee symptoms, particularly in those who are obese and who have OA. Although losing weight is potentially beneficial for symptom improvement, the effects were more modest. Avoiding weight gain is important in managing knee symptoms. PMID- 22674833 TI - Honokiol and magnolol stimulate glucose uptake by activating PI3K-dependent Akt in L6 myotubes. AB - Honokiol and magnolol, ingredients of Magnolia officinalis, which is used in traditional Chinese and Japanese medicines, have been reported to have antioxidant, anticancer, and antiangiogenic effects. Effects of these compounds on glucose metabolism in adipocytes have also been reported. However, their effects on skeletal muscle glucose uptake and the underlying molecular mechanisms are still unknown. Here, we investigated the direct effects and signaling pathways activated by honokiol and magnolol in skeletal muscle cells using L6 myotubes. We found that honokiol and magnolol dose-dependently acutely stimulated glucose uptake without synergistic effects of combined administration in L6 myotubes. Treatment with honokiol and magnolol also stimulated glucose transporter-4 translocation to the cell surface. Honokiol- and magnolol stimulated glucose uptake was blocked by the phosphatidylinositol-3 kinase inhibitor, wortmannin. Both honokiol and magnolol stimulated Akt phosphorylation, a key element in the insulin signaling pathway, which was completely inhibited by wortmannin. These results suggest that honokiol and magnolol might have beneficial effects on glucose metabolism by activating the insulin signaling pathway. PMID- 22674834 TI - Stereoselective interactions between local anesthetics and ion channels. AB - Local anesthetics are useful probes of ion channel function and structure. Stereoselective interactions are especially interesting because they can reveal three-dimensional relationships between drugs and channels with otherwise identical biophysical and physicochemical properties. Furthermore, stereoselectivity suggests direct and specific receptor-mediated action, and identification of such stereospecific interactions may have important clinical consequences. The fact that drug targets are able to discriminate between the enantiomers present in a racemic drug is the consequence of the ordered asymmetric macromolecular units that form living cells. However, almost 25% of the drugs used in the clinical practice are racemic mixtures, and their individual enantiomers frequently differ in both their pharmacodynamic and pharmacokinetic profiles. Moreover, their effects can be similar to or different from the pharmacological effect of the drug and may contribute to the undesired effects of the drug. In other cases, the pharmacological effects induced by the two enantiomers on the molecular target are opposite. In the present manuscript, we will review the stereoselective effects of bupivacaine-like local anesthetics on cardiac sodium and potassium channels. PMID- 22674835 TI - The neural plasticity of early-passage human bone marrow-derived mesenchymal stem cells and their modulation with chromatin-modifying agents. AB - Mesenchymal stem cells (MSCs) in their immature state express a variety of genes of the three germ layers at relatively low or moderate levels that might explain their phenomenal plasticity. Numerous recent studies have demonstrated that under the appropriate conditions in vitro and in vivo the expression of different sets of these genes can be upregulated, turning MSCs into variety of cell lineages of mesodermal, ectodermal and endodermal origin. While transdifferentiation of MSCs is still controversial, these unique properties make MSCs an ideal autologous source of easily reprogrammable cells. Recently, using the approach of cell reprogramming by biological active compounds that interfere with chromatin structure and function, as well as with specific signalling pathways that promote neural fate commitment, we have been able to generate neural-like cells from human bone marrow (BM)-derived MSCs (hMSCs). However, the efficiency of neural transformation of hMSCs induced by this approach gradually declined with passaging. To elucidate the mechanisms that underlie the higher plasticity of early-passage hMSCs, comparative analysis of the expression levels of several pluripotent and neural genes was conducted for early- and late-passage hMSCs. The results demonstrated that early-passage hMSCs expressed the majority of these genes at low and moderate levels that gradually declined at late passages. Neural induction further increased the expression of some of these genes in hMSCs, accompanied by morphological changes into neural-like cells. We concluded that low and moderate expression of several pluripotent and neural genes in early passage hMSCs could explain their higher plasticity and pliability for neural induction. PMID- 22674836 TI - Occupational therapy in Oman: the impact of cultural dissonance. AB - Occupational therapy theory and philosophy are broadly considered to be based on Western cultural values. In contrast, the application of theory and practice in the Sultanate of Oman, historically based on traditional Middle Eastern and Islamic cultural values, provides a case exemplar, which highlights both paradigmatic differences and cultural dissonance. Drawing on the experiences of occupational therapists working in Oman, this study found that the application of therapeutic goals aimed at patient independence and autonomy were difficult to achieve in an environment where family duty and responsibility for care were highly prized. Dressing and cooking assessments were challenging, and issues related to gender proved problematic. Therapists found the need to adapt practice to acknowledge these differences, and to adopt pragmatic problem-solving strategies, without resolving the underpinning philosophical contradictions. Occupational therapy in Oman is under-researched; further work is needed to confirm the cross-cultural validity of specific assessments and practice models. PMID- 22674837 TI - Preparative purification of peoniflorin and albiflorin from peony rhizome using macroporous resin and medium-pressure liquid chromatography. AB - Peoniflorin (PF) and albiflorin (AF) are two principal components of Paeonia species, which exhibit various biological activities such as improvement of blood circulation and immunoregulating function. To further utilization of waste parts of peony plants, an efficient method for preparative purification of these two ingredients from white peony rhizome was developed based on macroporous resin (MAR) and medium-pressure liquid chromatography (MPLC). The separation characteristics of nine typical MARs were investigated by static adsorption/desorption experiments, and LX38 was revealed as optimal one. Further static experiments with LX38 resin indicated that the adsorbents fitted well to the pseudo-second-order kinetics model and both Langmuir and Freundlich isotherm models. Based on the optimal process parameters, a large-scale preparation was successfully applied. After one run treatment with LX38, the contents of PF and AF were increased 15-fold to 24.5 and 16.8% in the refined extract, respectively. Both purified compounds were obtained from refined extract by reversed-phase MPLC at second-stage separation. The process developed is better because of its low cost, high efficiency, and procedural simplicity making it a potential approach for large-scale production of PF and AF for their further applications in functional foods and pharmaceuticals. PMID- 22674838 TI - Enantioselective and collective syntheses of xanthanolides involving a controllable dyotropic rearrangement of cis-beta-lactones. AB - Let's swap: a scalable, atom-economic, enantio-, and diastereoselective synthetic route to trisubstituted gamma-butyrolactones based on a Wagner-Meerwein-type dyotropic rearrangement of cis-beta-lactones is described. This methodology was applied in efficient and protecting-group-free formal syntheses and total syntheses of various xanthanolide natural products. PMID- 22674839 TI - Visitors or visits? An examination of zoo visitor numbers using the case study of Australia. AB - Usually cited in reference to the potential reach of zoo education, one of the popular figures for global zoo visitation is that 600 million people visit zoos annually. However, this number needs clarification on two fronts. First, there are many zoo visitors who are not included in the calculation because they visited a zoo that was not included in the count. Second, it does not take into consideration the people visit either the same or different zoos more than once annually. Using data collected from several sources, including zoo visitors themselves, this article focuses on one country--Australia--that contributes 15.6 million to the visitation total, and contends that the correct number of unique annual zoo visitors to Australian zoos is likely to be between 8 and 10 million. However, rather than suggesting an overemphasis on the potential of zoos for educating visitors, having regular repeat visitors represents a distinct advantage for zoos, allowing for progressive education opportunities. PMID- 22674840 TI - The accessibility of vulnerable groups to health services in Greece: a Delphi study on the perceptions of health professionals. AB - BACKGROUND: Problems of accessibility to healthcare services notably affect certain population groups such as poor and unemployed people, migrants and minorities, thus having a negative impact on their health. The aim of this study was to investigate these problems from the perspective of health professionals and to formulate empirically informed suggestions to solve the issue. METHODS: Primary data were collected in 2010-2011 by using a panel of 36 experienced health professionals around Greece. A two-round Delphi method was undertaken to achieve the objectives of the study. The first questionnaire investigated the factors that hinder accessibility to health services. The second round aimed at determining the relative importance of each of the factors emerging in the first round. RESULTS: The group of experts identified 345 factors in the first round, which were grouped in 55 statements. Consensus was achieved in 22 statements. The study revealed important issues, and health professionals proposed a number of actions to eliminate the accessibility problems. CONCLUSIONS: The use of medical interpreters and cultural mediators, transcultural education and stronger linkages among medical facilities are important to reduce accessibility problems. Restructuring primary healthcare and better documenting of the beneficiaries could also improve the quality of provided healthcare services. PMID- 22674841 TI - Income-related inequity in healthcare utilisation among individuals with cardiovascular disease in England-accounting for vertical inequity. AB - Economic analyses of equity which focus solely on horizontal inequity offer a partial assessment of socioeconomic inequity in healthcare use. We analyse income related inequity in cardiovascular disease-related healthcare utilisation by individuals reporting cardiovascular disease in England, including both horizontal and vertical aspects. For the analysis of vertical inequity, we use target groups to estimate the appropriate relationship between healthcare needs and use. We find that including vertical inequity considerations may lead us to draw different conclusions about the nature and extent of income-related inequity. After accounting for vertical inequity in addition to horizontal inequity, there is no longer evidence of inequity favouring the poor for nurse visits, whereas there is some evidence that doctor visits and inpatient stays are concentrated among richer individuals. The estimates of income-related inequity for outpatient visits, electrocardiography tests and heart surgery become even more pro-rich when accounting for vertical inequity. PMID- 22674842 TI - A mechanistic study of the utilization of arachno-diruthenaborane [(Cp*RuCO)2B2H6] as an active alkyne-cyclotrimerization catalyst. AB - The reaction of nido-[1,2-(Cp*RuH)(2)B(3)H(7)] (1a, Cp*=eta(5)-C(5)Me(5)) with [Mo(CO)(3)(CH(3)CN)(3)] under mild conditions yields the new metallaborane arachno-[(Cp*RuCO)(2)B(2)H(6)] (2). Compound 2 catalyzes the cyclotrimerization of a variety of internal- and terminal alkynes to yield mixtures of 1,3,5- and 1,2,4-substituted benzenes. The reactivities of nido-1a and arachno-2 with alkynes demonstrates that a change in geometry from nido to arachno drives a change in the reaction from alkyne-insertion to catalytic cyclotrimerization, respectively. Density functional calculations have been used to evaluate the reaction pathways of the cyclotrimerization of alkynes catalyzed by compound 2. The reaction involves the formation of a ruthenacyclic intermediate and the subsequent alkyne-insertion step is initiated by a [2+2] cycloaddition between this intermediate and an alkyne. The experimental and quantum-chemical results also show that the stability of the metallacyclic intermediate is strongly dependent on the nature of the substituents that are present on the alkyne. PMID- 22674843 TI - Reproducibility, validity, and responsiveness of the hip outcome score in patients with end-stage hip osteoarthritis. AB - OBJECTIVE: To evaluate reproducibility, validity, and responsiveness of the Hip Outcome Score (HOS) in patients with end-stage hip osteoarthritis. METHODS: In a cohort of 157 consecutive patients (mean age 66 years; 79 women) undergoing total hip replacement, the HOS was tested for the following measurement properties: feasibility (percentage of evaluable questionnaires), reproducibility (intraclass correlation coefficient [ICC] and standard error of measurement [SEM]), construct validity (correlation with the Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC], Oxford Hip Score [OHS], Short Form 12 health survey, and University of California, Los Angeles activity scale), internal consistency (Cronbach's alpha), factorial validity (factor analysis), floor and ceiling effects, and internal and external responsiveness at 6 months after surgery (standardized response mean and change score correlations). RESULTS: Missing items occurred frequently. Five percent to 6% of the HOS activities of daily living (ADL) subscales and 20-32% of the sport subscales could not be scored. ICCs were 0.92 for both subscales. SEMs were 1.8 points (ADL subscale) and 2.3 points (sport subscale). Highest correlations were found with the OHS (r = 0.81 for ADL subscale and r = 0.58 for sport subscale) and the WOMAC physical function subscale (r = 0.83 for ADL subscale and r = 0.56 for sport subscale). Cronbach's alpha was 0.93 and 0.88 for the ADL and sport subscales, respectively. Neither unidimensionality of the subscales nor the 2-factor structure was supported by factor analysis. Both subscales showed good internal and external responsiveness. CONCLUSION: The HOS is reproducible and responsive when assessing patients with end-stage hip osteoarthritis in whom the items are relevant. However, based on the large proportion of missing data and the findings of the factor analysis, we cannot recommend this questionnaire for routine use in this target group. PMID- 22674844 TI - Geographic variability in response to azinphos-methyl in field-collected populations of Cydia pomonella (Lepidoptera: Tortricidae) from Argentina. AB - BACKGROUND: Resistance to insecticides has been related to application history, genetic factors of the pest and the dynamic within the treated area. The aim of this study was to assess the geographic variation in azinphos-methyl response and the role of esterase and cytochrome P450 monooxygenase enzymes in codling moth populations collected within different areas of the Rio Negro and Neuquen Valley, Argentina. RESULTS: Diapausing field-collected populations showed resistance ratios at the LC(50) that were 0.7-8.7 times higher than that of the susceptible strain. Mean esterase (EST) and cytochrome P450 monooxygenase activities (expressed as alpha-N min(-1) mg(-1) prot(-1) and pg 7-OHC insect(-1) min(-1) respectively) were significantly correlated with LD(50) values from the field collected populations. In addition, azinphos-methyl response was associated with the geographic area where the insect population was collected: populations from isolated and more recent productive areas presented significantly lower resistance ratios in comparison with populations from older and more intensive productive areas. CONCLUSION: The populations assayed presented different resistance levels to azinphos-methyl. The response was highly correlated with the orchard's geographic location. EST and ECOD activities were involved in azinphos methyl response in the given region. PMID- 22674846 TI - Continuous synthesis and purification by direct coupling of a flow reactor with simulated moving-bed chromatography. AB - Continuous synthesis meets continuous purification to produce pure products from crude reaction mixtures. In the nucleophilic aromatic substitution of 2,4 difluoronitrobenzene with morpholine the desired monosubstituted product can be continuously separated from the byproducts in a purity of over 99 % by coupling a flow reactor to a simulated moving bed (SMB) chromatography module. PMID- 22674845 TI - Sphingosine-1-phosphate signaling in physiology and diseases. AB - Sphingosine-1-phosphate (S1P), which acts as both the extracellular and intracellular messenger, exerts pleiotropic biological activities including regulation of formation of the vasculature, vascular barrier integrity, and lymphocyte trafficking. Many of these S1P actions are mediated by five members of the G protein-coupled S1P receptors (S1P(1) -S1P(5) ) with overlapping but distinct coupling to heterotrimeric G proteins. The biological activities of S1P are based largely on the cellular actions of S1P on migration, adhesion, and proliferation. Notably, S1P often exhibits receptor subtype-specific, bimodal effects in these cellular actions. For example, S1P(1) mediates cell migration toward S1P, that is, chemotaxis, via G(i) /Rac pathway whereas S1P(2) mediates inhibition of migration toward a chemoattractant, that is, chemorepulsion, via G(12/13) /Rho pathway, which induces Rac inhibition. In addition, S1P(1) mediates stimulation of cell proliferation through the G(i) -mediated signaling pathways including phosphatidylinositol 3-kinase (PI3K)/Akt and ERK whereas S1P(2) mediates inhibition of cell proliferation through mechanisms involving G(12/13) /Rho/Rho kinase/PTEN-dependent Akt inhibition. These differential effects of S1P receptor subtypes on migration and proliferation lead to bimodal regulation of various biological responses. An observed biological response is likely determined by an integrated outcome of the counteracting signals input by S1P receptor subtypes. More recent studies identified the new intracellular targets of S1P including the inflammatory signaling molecule TRAF2 and histone deacetylases HDAC1 and HDAC2. These interactions of S1P regulate NF-kappaB activity and gene expression, respectively. Development of S1P receptor agonists and antagonists with improved receptor subtype-selectivity, inhibitors, or modulators of sphingolipid-metabolizing enzymes, and their optimal drug delivery system provide novel therapeutic tactics. PMID- 22674847 TI - Pressure as a denaturing agent in studies of single-point mutants of an amyloidogenic protein human cystatin c. AB - Recently, we presented a convenient method combining a deuterium-hydrogen exchange and electrospray mass spectrometry for studying high-pressure denaturation of proteins (Stefanowicz et al., Biosci Rep 2009; 30:91-99). Here, we present results of pressure-induced denaturation studies of an amyloidogenic protein-the wild-type human cystatin C (hCC) and its single-point mutants, in which Val57 residue from the hinge region was substituted by Asn, Asp or Pro, respectively. The place of mutation and the substituting residues were chosen mainly on a basis of theoretical calculations. Observation of H/D isotopic exchange proceeding during pressure induced unfolding and subsequent refolding allowed us to detect differences in the proteins stability and folding dynamics. On the basis of the obtained results we can conclude that proline residue at the hinge region makes cystatin C structure more flexible and dynamic, what probably facilitates the dimerization process of this hCC variant. Polar asparagine does not influence stability of hCC conformation significantly, whereas charged aspartic acid in 57 position makes the protein structure slightly more prone to unfolding. Our experiments also point out pressure denaturation as a valuable supplementary method in denaturation studies of mutated proteins. PMID- 22674848 TI - Enantioselective analysis of ofloxacin enantiomers by partial-filling capillary electrophoresis with bacteria as chiral selectors. AB - The enantiomeric separation of ofloxacin enantiomers (OFLX) was achieved by using capillary electrophoresis partial-filled with Escherichia coli, Pseudomonas aeruginosa (Gram-negative), and Staphylococcus aureus (Gram-positive) as chiral selectors. Experimental parameters, including the concentration of background electrolyte, applied voltage, length of the filled bacteria plug, and pH of the buffer, were intensively investigated. Baseline separation of OFLX could be achieved within 7 min by using E. coli and P. aeruginosa as chiral selectors under the following conditions: electrophoretic buffer composed of 10 mM phosphate buffer at pH 7.4, applied voltage at 15 kV, and the bacteria (6.0 * 10(8) cells/mL) were injected into the capillary by gravity with injection height of 17.5 cm for 180 s (E. coli), 300 s (P. aeruginosa), and 300 s (S. aureus), respectively. E. coli and P. aeruginosa had better chiral selectivity for OFLX than S. aureus, which was in good agreement with OFLX having better antimicrobial activity on Gram-negative rather than Gram-positive bacteria. A novel method was developed for the enantioselective separation of enantiomers using bacteria as chiral selectors, which provides a new approach for antimicrobials enantioselective analysis, chiral pharmacodynamics, and chiral pharmacokinetics studies. PMID- 22674849 TI - Nucleated cells circulating in the peripheral blood contribute to the repair of osteochondral defects only in the early phase of healing. AB - The role of cells circulating in the peripheral blood to participate in the natural repair process of osteochondral defects was evaluated in a green fluorescent protein (GFP) transgenic and wild rat parabiosis model. Two weeks after the parabiosis operation, vascular communication between the conjoined rats was confirmed by flow-cytometry analysis. A 1.5 mm diameter and 1.0 mm depth osteochondral defect was made in the patellar groove of each rat femoral bone. Histological examination was performed at 1, 2, 4 and 24 weeks following surgery. In the early postoperative phase (1-4 weeks) there were GFP-negative and positive cells in the defects of both parabiotic rats. GFP-positive chondrocytes were confirmed partly in the repair tissue of the wild parabiotic rat. In the late postoperative phase (24 weeks), the repaired defects were occupied by cells originating from the adjacent tissue and not from the peripheral blood. The ratio of cells originating from the peripheral blood was approximately 30-40% in the repair tissue at 1 week after surgery, reduced to 0-7% at 24 weeks. From these results it is confirmed that cells circulating in the peripheral blood contributed to the repair of the osteochondral defects, particularly in the early phase of healing. Thus, peripheral blood not only supplies the factors needed for repair but also provides a cell population involved in the wound-healing process. PMID- 22674850 TI - Cerebrospinal fluid proteomic patterns discriminate Parkinson's disease and multiple system atrophy. AB - The differential diagnosis of Parkinson's disease and multiple system atrophy can be challenging, especially in the early stages of the diseases. We developed a proteomic profiling strategy for parkinsonian diseases using mass spectrometry analysis for magnetic-bead-based enrichment of cerebrospinal fluid peptides/proteins and subsequent multivariate statistical analysis. Cerebrospinal fluid was obtained from 37 patients diagnosed with Parkinson's disease, 32 patients diagnosed with multiple system atrophy, and 26 patients diagnosed with other neurological diseases as controls. The samples were from the first cohort and the second cohort. Cerebrospinal fluid peptides/proteins were purified with C8 magnetic beads, and spectra were obtained by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Principal component analysis and support vector machine methods are used to reduce dimension of the data and select features to classify diseases. Cerebrospinal fluid proteomic profiles of Parkinson's disease, multiple system atrophy, and control were differentiated from each other by principal component analysis. By building a support vector machine classifier, 3 groups were classified effectively with good cross validation accuracy. The model accuracy was well preserved for both cases, training by the first cohort and validated by the second cohort and vice versa. Receiver operating characteristics proved that the peak of m/z 6250 was the most important to differentiate multiple system atrophy from Parkinson's disease, especially in the early stages of the disease. A proteomic pattern classification method can increase the accuracy of clinical diagnosis of Parkinson's disease and multiple system atrophy, especially in the early stages. PMID- 22674851 TI - Zeolite-supported gold nanoparticles for selective photooxidation of aromatic alcohols under visible-light irradiation. AB - With new photocatalysts of gold nanoparticles supported on zeolite supports (Au/zeolite), oxidation of benzyl alcohol and its derivatives into the corresponding aldehydes can proceed well with a high selectivity (99 %) under visible-light irradiation at ambient temperature. Au/zeolite photocatalysts were characterised by UV/Vis, X-ray photoelectron spectroscopy (XPS), TEM, XRD, energy dispersive spectroscopy (EDS), Brauner-Emmet-Teller (BET) analyses, IR and Raman techniques. The surface plasmon resonance (SPR) effect of gold nanoparticles, the adsorption capability of zeolite supports and the molecular polarities of aromatic alcohols were demonstrated to have an essential correlation with the photocatalytic performances. In addition, the effects of light intensity, wavelength range and the role of molecular oxygen were investigated in detail. The kinetic study indicated that the visible-light irradiation required much less apparent activation energy for photooxidation compared with thermal reaction. Based on the characterisation data and the photocatalytic performances, we proposed a possible photooxidation mechanism. PMID- 22674852 TI - Impacts of chemical crop protection applications on related CO(2) emissions and CO(2) assimilation of crops. AB - BACKGROUND: A major global challenge is to provide agricultural production systems that are able to sustain growing demands for food, feed, fibre and renewable raw materials without exacerbating climate change. Detailed and reliable data on the CO(2) balance of different agricultural management activities and inputs as a basis to quantify carbon footprints of agriculture are still lacking. This study aims to fill this gap further by quantifying the net balance of emitted and assimilated CO(2) due to the application of crop protection treatments on the farm, and by assessing their partial contribution to GHG emissions and mitigation in agriculture. The study focuses on key agricultural crops including wheat, corn, oilseeds and sugar crops. RESULTS: The final CO(2) balance, considering GHG emissions due to on-farm CPP treatment in comparison with CO(2) storage in additional biomass, CO(2) protected with respect to agrotechnical inputs and land inputs and CO(2) saved with respect to associated global land use changes, is positive and may reach multiples of up to nearly 2000. CONCLUSION: The results highlight the importance of the positive yield effects of the CPP programme applications on the farm, resulting in additional assimilated biomass at the farm level and less land use changes at the global level, and thus lower pressure on environmentally important indicators of overall agricultural sustainability. PMID- 22674853 TI - Minimum clinically important improvement and patient acceptable symptom state in pain and function in rheumatoid arthritis, ankylosing spondylitis, chronic back pain, hand osteoarthritis, and hip and knee osteoarthritis: Results from a prospective multinational study. AB - OBJECTIVE: To estimate the minimum clinically important improvement (MCII) and patient acceptable symptom state (PASS) values for 4 generic outcomes in 5 rheumatic diseases and 7 countries. METHODS: We conducted a multinational (Australia, France, Italy, Lebanon, Morocco, Spain, and The Netherlands) 4-week cohort study involving 1,532 patients who were prescribed nonsteroidal antiinflammatory drugs for ankylosing spondylitis, chronic back pain, hand osteoarthritis, hip and/or knee osteoarthritis, or rheumatoid arthritis. The MCII and PASS values were estimated with the 75th percentile approach for 4 generic outcomes: pain, patient global assessment, functional disability, and physician global assessment, all normalized to a 0-100 score. RESULTS: For the whole sample, the estimated MCII values for absolute change at 4 weeks were -17 (95% confidence interval [95% CI] -18, -15) for pain; -15 (95% CI -16, -14) for patient global assessment; -12 (95% CI -13, -11) for functional disability assessment; and -14 (95% CI -15, -14) for physician global assessment. For the whole sample, the estimated PASS values were 42 (95% CI 40, 44) for pain; 43 (95% CI 41, 45) for patient global assessment; 43 (95% CI 41, 44) for functional disability assessment; and 39 (95% CI 37, 40) for physician global assessment. Estimates were consistent across diseases and countries (for subgroups >=20 patients). CONCLUSION: This work allows for promoting the use of values of MCII (15 of 100 for absolute improvement, 20% for relative improvement) and PASS (40 of 100) in reporting the results of trials of any of the 5 involved rheumatic diseases with pain, patient global assessment, physical function, or physician global assessment used as outcome criteria. PMID- 22674854 TI - Restoration of caveolin-1 expression suppresses growth, membrane-type-4 metalloproteinase expression and metastasis-associated activities in colon cancer cells. AB - Caveolin-1 (cav-1) and flotillin-1 are two major structural proteins associated with lipid rafts in mammalian cells. The membrane-type matrix metalloproteinases (MT-MMPs) are expressed at the cell surface, hydrolyze extracellular matrix, and play an important role in cancer cell migration and metastasis. Expression of cav 1, flotillin-1, and MT4-MMP in lysates and lipid rafts of LS174T and HM-7 colon cancer cells was determined. The impact of restoration of cav-1 expression on proliferation, adhesion, motility in vitro, and growth of implanted tumors in vivo was characterized. Cav-1 is not expressed in lipid rafts of the highly metastatic colon cancer cell line (HM-7), but expressed in cytosolic fractions of the parental lower metastatic cell line (LS174T). In contrast, MT4-MMP was expressed in lipid rafts of HM-7 cells but not in LS174T cells. Overexpression of cav-1 in HM-7 cells down-regulate proliferation, viability, wound closure, adhesion to laminin, invasion, and development of filopodial and lamellipodial structures in a dose-dependent manner. Cav-1 positive HM-7 clones ceased to express MT4-MMP in their lipid rafts. Comparative proteomic analyses of lipid rafts from cav-1 positive and cav-1 negative cells demonstrated de novo expression of flotillin-1 only on the cells expressing cav-1. Xenografting control cells devoid of cav-1 in nude mice induced development of bigger tumors expressing higher levels of proliferating cell nuclear antigen as compared to mice injected with cells expressing the highest cav-1 levels. We conclude that cav-1 orchestrates and reorganize several proteins in lipid rafts, activities directly associated with reduced tumorigenic and metastatic ability of colon cancer cells. PMID- 22674855 TI - Ligand binding by PDZ domains. AB - The postsynaptic density protein-95/disks large/zonula occludens-1 (PDZ) protein domain family is one of the most common protein-protein interaction modules in mammalian cells, with paralogs present in several hundred human proteins. PDZ domains are found in most cell types, but neuronal proteins, for example, are particularly rich in these domains. The general function of PDZ domains is to bring proteins together within the appropriate cellular compartment, thereby facilitating scaffolding, signaling, and trafficking events. The many functions of PDZ domains under normal physiological as well as pathological conditions have been reviewed recently. In this review, we focus on the molecular details of how PDZ domains bind their protein ligands and their potential as drug targets in this context. PMID- 22674856 TI - Sequence divergence in the 3'-untranslated region has an effect on the subfunctionalization of duplicate genes. AB - Recent studies demonstrated that sequence divergence in both transcriptional regulatory region and coding region contributes to the subfunctionalization of duplicate gene. However, whether sequence divergence in the 3'-untranslated region (3'-UTR) has an impact on the subfunctionalization of duplicate genes remains unclear. Here, we identified two diverging duplicate vsx1 (visual system homeobox-1) loci in goldfish, named vsx1A1 and vsx1A2. Phylogenetic analysis suggests that vsx1A1 and vsx1A2 may arise from a duplication of vsx1 after the separation of goldfish and zebrafish. Sequence comparison revealed that divergence in both transcriptional and translational regulatory regions is higher than divergence in the introns. vsx1A2 expresses during blastula and gastrula stages and in adult retina but silences from segmentation stage to hatching stage, vsx1A1 starts expression from segmentation onward. Comparing to that zebrafish vsx1 expresses in all the developmental stages and in the adult retina, it appears that goldfish vsx1A1 and vsx1A2 are under going to share the functions of ancestral vsx1. The different but overlapping temporal expression patterns of vsx1A1 and vsx1A2 suggest that sequence divergence in the promoter region of duplicate vsx1 is not sufficient for partitioning the functions of ancestral vsx1. By comparing vsx1A1 and vsx1A2 3'-UTR-linked green fluorescent protein gene expression patterns, we demonstrated that the 3'-UTR of vsx1A1 remains but the 3' UTR of vsx1A2 has lost the capability of mediating bipolar cell specific expression during retina development. These results indicate that sequence divergence in the 3'-UTRs has a clear effect on subfunctionalization of the duplicate genes. PMID- 22674857 TI - Catalytic asymmetric synthesis of spirooxindoles by a mannich-type reaction of isothiocyanato oxindoles. AB - Easy access: a strontium/Schiff base complex as catalyst for the title reaction provided straightforward access to enantiomerically enriched spiro[imidazolidine 4,3'-oxindole] compounds, as well as a spiro[imidazoline-4,3'-oxindole] through a two-step conversion from the Mannich adduct. PMID- 22674858 TI - Computational design, construction, and characterization of a set of specificity determining residues in protein-protein interactions. AB - Proteins interact with different partners to perform different functions and it is important to elucidate the determinants of partner specificity in protein complex formation. Although methods for detecting specificity determining positions have been developed previously, direct experimental evidence for these amino acid residues is scarce, and the lack of information has prevented further computational studies. In this article, we constructed a dataset that is likely to exhibit specificity in protein complex formation, based on available crystal structures and several intuitive ideas about interaction profiles and functional subclasses. We then defined a "structure-based specificity determining position (sbSDP)" as a set of equivalent residues in a protein family showing a large variation in their interaction energy with different partners. We investigated sequence and structural features of sbSDPs and demonstrated that their amino acid propensities significantly differed from those of other interacting residues and that the importance of many of these residues for determining specificity had been verified experimentally. PMID- 22674860 TI - Physiotherapy health services research (PHSR): the road 'that must now be taken'. PMID- 22674859 TI - Highly defined multiblock copolypeptoids: pushing the limits of living nucleophilic ring-opening polymerization. AB - Advanced macromolecular engineering requires excellent control over the polymerization reaction. Living polymerization methods are notoriously sensitive to impurities, which makes a practical realization of such control very challenging. Reversible-deactivation radical polymerization methods are typically more robust, but have other limitations. Here, we demonstrate by repeated (>=10 times) chain extension the extraordinary robustness of the living nucleophilic ring-opening polymerization of N-substituted glycine N-carboxyanhydrides, which yields polypeptoids. We observe essentially quantitative end-group fidelity under experimental conditions that are comparatively easily managed. This is employed to synthesize a pentablock quinquiespolymer with high definition. PMID- 22674861 TI - A process of subgroup identification in non-specific low back pain using a standard clinical examination and cluster analysis. AB - BACKGROUND AND PURPOSE: Non-specific low back pain (NSLBP) accounts for over 85% of all low back pain. Homogenous subgroups may exist within this diagnosis. This study derived a clinical examination and evaluated the examination's ability to identify homogenous subgroups in NSLBP. METHODS: Patients with NSLBP were examined using a standardized clinical examination. Each patient was examined by two physiotherapists. Data were analysed for item reliability and the presence of distinct subgroups using cluster analysis. Cross-validation of the clusters identified was conducted. RESULTS: Three hundred and one patients were examined. The inter-tester reliability of the majority of items was moderate to substantial (52% of items with kappa > 0.40). A K-means cluster analysis of the two data sets revealed agreement on the presence of two subgroups. One group (n = 47, 16%) had higher fear avoidance beliefs, anxiety and disability. They were more likely to be provoked by pain provocative tests. They were also more likely to be judged as having central sensitization and a dominant psychosocial component to their presentation. CONCLUSION: The identification of a group of hypervigilant NSLBP patients should allow the interventions to be targeted towards this group. A valid, standardized clinical examination does contribute to the diagnostic management of NSLBP. PMID- 22674864 TI - In vivo cartilage repair using adipose-derived stem cell-loaded decellularized cartilage ECM scaffolds. AB - We have previously reported a natural, human cartilage ECM (extracellular matrix) derived three-dimensional (3D) porous acellular scaffold for in vivo cartilage tissue engineering in nude mice. However, the in vivo repair effects of this scaffold are still unknown. The aim of this study was to further explore the feasibility of application of cell-loaded scaffolds, using autologous adipose derived stem cells (ADSCs), for cartilage defect repair in rabbits. A defect 4 mm in diameter was created on the patellar groove of the femur in both knees, and was repaired with the chondrogenically induced ADSC-scaffold constructs (group A) or the scaffold alone (group B); defects without treatment were used as controls (group C). The results showed that in group A all defects were fully filled with repair tissue and at 6 months post-surgery most of the repair site was filled with hyaline cartilage. In contrast, in group B all defects were partially filled with repair tissue, but only half of the repair tissue was hyaline cartilage. Defects were only filled with fibrotic tissue in group C. Indeed, histological grading score analysis revealed that an average score in group A was higher than in groups B and C. GAG and type II collagen content and biomechanical property detection showed that the group A levels approached those of normal cartilage. In conclusion, ADSC-loaded cartilage ECM scaffolds induced cartilage repair tissue comparable to native cartilage in terms of mechanical properties and biochemical components. PMID- 22674865 TI - A flexible copper(I)-complexed [4]rotaxane containing two face-to-face porphyrinic plates that behaves as a distensible receptor. AB - A new cyclic [4]rotaxane composed of two flexible bis-macrocycles and two rigid axles is described. Each bis-macrocycle consists of two rings attached to antipodal meso positions of a central Zn porphyrin through single C-C bonds. Each ring incorporates a 2,9-diphenyl-1,10-phenanthroline chelation site. The axles contain two coplanar bidentate sites derived from the 2,2'-bipyridine motif. The building blocks were assembled by using a one-pot threading-and-stoppering reaction, which afforded the [4]rotaxane in 50% yield. The "gathering-and threading" effect of copper(I) was utilised in the formation of a [4]pseudorotaxane, which was immediately converted to the corresponding [4]rotaxane by a quadruple CuAAC stoppering reaction. The rotaxane contains two face-to-face zinc porphyrins, which allowed the coordination of ditopic guest substrates. The rotaxane host showed remarkable flexibility and was able to adjust its conformation to the guest size. It can be distended and accommodate rod-like guests of 2.6 to 15.8 A in length. PMID- 22674866 TI - Transovarial biotransference of etoxazole through a terrestrial trophic web. AB - BACKGROUND: Transovarial transport is defined as the passage of chemicals from the maternal body to eggs within the ovaries. Little is known about the effects of transovarial transport on non-target species. This study evaluates etoxazole (a transovarial acaricidal compound) on a terrestrial trophic web consisting of a ubiquitous phytophagous mite, Tetranychus urticae Koch, and three species of predatory mites. RESULTS: Predatory mite females that consumed eggs laid by etoxazole-treated T. urticae also produced infertile eggs. There was a negative relationship between the proportion of etoxazole-treated T. urticae females and the instantaneous rate of predatory mite increase at the population level (r(2) = 0.86). Reduced fertility of etoxazole-treated T. urticae females continued for 18 days following application. Eggs laid by etoxazole-treated T. urticae females remained toxic to predatory mite females for 42 days after treatment. CONCLUSIONS: Transovarial transport could lead to magnification in the ecosystem by enhancing both bioavailability and movement of an active ingredient. The potential for enhancement of residual activity by terrestrial organisms and its significance once reaching the food web should be taken into account for new classes of acaricides and insecticides. PMID- 22674868 TI - Genetic variants at 4q23 and 12q24 are associated with head and neck cancer risk in China. AB - A recent genome-wide association study (GWAS) reported significant associations of several novel genetic variants with risk of upper aerodigestive tract (UADT) cancers including head and neck cancer (HNC) in Europeans. However, these findings have not been confirmed in other populations including Chinese. According to the findings from the GWAS and other publications, we genotyped six genetic variants (rs1494961, rs1229984, rs1789924, rs971074, rs4767364, and rs671) in a case-control study with 397 HNC cases and 900 controls in China, by using the TaqMan allelic discrimination assay. We found that rs1229984 at 4q23 significantly increased the risk of HNC [dominant model: adjusted odds ratio (OR) = 1.34, 95% confidence interval (CI) = 1.05-1.71; additive model: adjusted OR = 1.24, 95% CI = 1.04-1.50], while rs671 at 12q24 significantly decreased the risk of HNC (recessive model: adjusted OR = 0.46, 95% CI = 0.25-0.85). Furthermore, when these two loci were evaluated together by the number (0-4) of putative risk alleles (rs1229984 G and rs671 G), a significant locus-dosage effect was found between the groups and risk of HNC (Ptrend = 0.016). Compared with the "0-1" group, groups with "2" risk alleles and "3-4" risk alleles significantly increased the risk of HNC with adjusted ORs of 1.17 (95% CI = 0.84-1.64) and 1.51 (95% CI = 1.06-2.15), respectively. However, no significant association was detected between other four variants (rs1494961, rs1789924, rs971074, and rs4767364) and HNC risk. These findings suggest that rs1229984 at 4q23 and rs671 at 12q24 may serve as candidate markers for susceptibility to HNC in Chinese population. PMID- 22674867 TI - A comparison of short-term and long-term air pollution exposure associations with mortality in two cohorts in Scotland. AB - BACKGROUND: Air pollution-mortality risk estimates are generally larger at longer term, compared with short-term, exposure time scales. OBJECTIVE: We compared associations between short-term exposure to black smoke (BS) and mortality with long-term exposure-mortality associations in cohort participants and with short term exposure-mortality associations in the general population from which the cohorts were selected. METHODS: We assessed short-to-medium-term exposure mortality associations in the Renfrew-Paisley and Collaborative cohorts (using nested case-control data sets), and compared them with long-term exposure mortality associations (using a multilevel spatiotemporal exposure model and survival analyses) and short-to-medium-term exposure-mortality associations in the general population (using time-series analyses). RESULTS: For the Renfrew Paisley cohort (15,331 participants), BS exposure-mortality associations were observed in nested case-control analyses that accounted for spatial variations in pollution exposure and individual-level risk factors. These cohort-based associations were consistently greater than associations estimated in time-series analyses using a single monitoring site to represent general population exposure {e.g., 1.8% [95% confidence interval (CI): 0.1, 3.4%] vs. 0.2% (95% CI: 0.0, 0.4%) increases in mortality associated with 10-MUg/m3 increases in 3-day lag BS, respectively}. Exposure-mortality associations were of larger magnitude for longer exposure periods [e.g., 3.4% (95% CI: -0.7, 7.7%) and 0.9% (95% CI: 0.3, 1.5%) increases in all-cause mortality associated with 10-MUg/m3 increases in 31 day BS in case-control and time-series analyses, respectively; and 10% (95% CI: 4, 17%) increase in all-cause mortality associated with a 10-MUg/m3 increase in geometic mean BS for 1970-1979, in survival analysis]. CONCLUSIONS: After adjusting for individual-level exposure and potential confounders, short-term exposure-mortality associations in cohort participants were of greater magnitude than in comparable general population time-series study analyses. However, short term exposure-mortality associations were substantially lower than equivalent long-term associations, which is consistent with the possibility of larger, more persistent cumulative effects from long-term exposures. PMID- 22674869 TI - Asymmetric catalytic alkynylation of acetaldehyde: application to the synthesis of (+)-tetrahydropyrenophorol. PMID- 22674870 TI - Association between body mass index and anti-citrullinated protein antibody positive and anti-citrullinated protein antibody-negative rheumatoid arthritis: results from a population-based case-control study. AB - OBJECTIVE: Being overweight or obese is associated with many chronic diseases, but previous studies of the association with rheumatoid arthritis (RA) have shown inconsistent results. The aim of this study was to investigate the association between body mass index (BMI) and the risk of developing the 2 main subtypes of RA. METHODS: At inclusion, cases and controls answered questions about their weight and height and donated blood samples. The presence of antibodies to citrullinated protein antigens (ACPAs) was analyzed among 2,748 cases and 3,444 controls (28% men). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using conditional logistic regression. RESULTS: Compared to those with normal weight (BMI <25 kg/m(2) ), the adjusted overall OR for developing ACPA negative RA was 1.1 (95% CI 0.9-1.3) for overweight individuals (BMI >=25 to <30 kg/m(2) ) and 1.4 (95% CI 1.1-1.9) for obese individuals (BMI >=30 kg/m(2) ). When stratified by sex, the OR for ACPA-negative RA for obese women was 1.6 (95% CI 1.2-2.2), and there was no association between obesity and ACPA-negative RA in men (OR 1.1, 95% CI 0.6-1.8). In obese men compared to men with normal weight, the OR for ACPA-positive RA was 0.6 (95% CI 0.3-0.9), while there was no association between BMI and ACPA-positive RA among women (OR 1.0, 95% CI 0.8 1.2). CONCLUSION: Our findings show that obesity is associated with developing ACPA-negative RA in women, and indicate an inverse association between BMI and ACPA-positive RA in men. PMID- 22674871 TI - Diffusion abnormalities in temporal lobes of children with temporal lobe epilepsy: a preliminary diffusional kurtosis imaging study and comparison with diffusion tensor imaging. AB - In this preliminary study, we aimed to investigate the abnormalities of water diffusion in children with temporal lobe epilepsy (TLE). Eight children with unilateral TLE (according to electroencephalography, EEG) and eight age- and sex matched controls were recruited. Diffusion tensor imaging (DTI)/diffusional kurtosis imaging (DKI) acquisitions were performed. Radial diffusivity (lambda(?)), axial diffusivity (lambda(?)), mean diffusivity (MD) and fractional anisotropy (FA) maps were calculated for both DTI and DKI, and radial kurtosis (K(?)), axial kurtosis (K(?)) and mean kurtosis (MK) maps were calculated for DKI only. Mann-Whitney test showed that, for white matter in the temporal lobe, DKI derived lambda(?) , MD and K(?) were significantly different in bilateral temporal lobes and EEG-abnormal and EEG-normal sides of the temporal lobe between patients and controls, whereas DTI showed no abnormalities. For gray matter, DKI detected significantly higher MD and MK in the same three comparisons, whereas DTI detected abnormalities only in the comparison between bilateral temporal lobes and between EEG-normal sides in cases and left-right matched sides in controls. No significant difference was observed between EEG-abnormal and EEG normal sides in cases. These preliminary results indicate that DKI is more sensitive than DTI for the detection of diffusion abnormalities in the temporal lobes of children with TLE, even when EEG signals are normal. These findings pave the way for the application of DKI for in-depth studies on TLE in children. PMID- 22674873 TI - Factors reported to influence fear of recurrence in cancer patients: a systematic review. AB - OBJECTIVE: Fear of cancer recurrence (FCR) is a significant psychological problem for cancer survivors. Some survivors experience FCR, which is both persistent and highly distressing. The aim of this systematic review was to identify the key factors associated with fear of recurrence among cancer patients. METHODS: A comprehensive literature search using keywords was performed with three databases, followed by an organic search to identify additional relevant articles. Included studies had a quantitative methodology presenting empirical findings focussed on adult cancer patients. A methodological quality assessment was performed for each study, and the strength of evidence was defined by the consistency of results. RESULTS: Forty-three studies met the inclusion criteria and are presented in this review. The most consistent predictor of elevated FCR was younger age. There was strong evidence for an association between physical symptoms and fear of cancer recurrence. Additional factors moderately associated with increased FCR included treatment type, low optimism, family stressors and fewer significant others. Inconsistent evidence was found for socio-demographic factors. CONCLUSIONS: Fear of cancer recurrence is a complex issue influenced by a multitude of factors, including demographic, clinical and psychological factors. However, some studies have reported contradictory evidence, and FCR has been measured using a range of scales, which can hamper comparison across studies. Further research is needed to clarify inconsistencies in the current published research. PMID- 22674872 TI - Kinesin tail domains are intrinsically disordered. AB - Kinesin motor proteins transport a wide variety of molecular cargoes in a spatially and temporally regulated manner. Kinesin motor domains, which hydrolyze ATP to produce a directed mechanical force along a microtubule, are well conserved throughout the entire superfamily. Outside of the motor domains, kinesin sequences diverge along with their transport functions. The nonmotor regions, particularly the tails, respond to a wide variety of structural and molecular cues that enable kinesins to carry specific cargoes in response to particular cellular signals. Here, we demonstrate that intrinsic disorder is a common structural feature of kinesins. A bioinformatics survey of the full-length sequences of all 43 human kinesins predicts that significant regions of intrinsically disordered residues are present in all kinesins. These regions are concentrated in the nonmotor domains, particularly in the tails and near sites for ligand binding or post-translational modifications. In order to experimentally verify these predictions, we expressed and purified the tail domains of kinesins representing three different families (Kif5B, Kif10, and KifC3). Circular dichroism and NMR spectroscopy experiments demonstrate that the isolated tails are disordered in vitro, yet they retain their functional microtubule-binding activity. On the basis of these results, we propose that intrinsic disorder is a common structural feature that confers functional specificity to kinesins. PMID- 22674874 TI - Functional monolithic materials for boronate-affinity chromatography via Schrock catalyst-triggered ring-opening metathesis polymerization. AB - Monolithic polymeric materials are prepared via ring-opening metathesis copolymerization of norborn-2-ene with 1,4,4a,5,8,8a-hexahydro-1,4,5,8-exo,endo dimethanonaphthalene in the presence of macro- and microporogens, that is, of n hexane and 1,2-dichloroethane, using the Schrock catalyst Mo(N-2,6-(2-Pr)(2) C(6) H(3) )(CHCMe(2) Ph)(OCMe(3) )(2) . Functionalization of the monolithic materials is accomplished by either terminating the living metal alkylidenes with various functional aldehydes or by post-synthesis grafting with norborn-5-en-2 ylmethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate. Finally, boronate-grafted monolithic columns (100 * 3 mm i.d.) are successfully applied to the affinity chromatographic separation of cis-diol-based biomolecules. PMID- 22674875 TI - Physiotherapy rehabilitation for individuals with lower limb amputation: a 15 year clinical series. AB - BACKGROUND AND PURPOSE: Individuals with amputations are a core group in Australian rehabilitation units that have a long index length of stay. The Repatriation General Hospital (RGH) offers general rehabilitation services to the population of Southern Adelaide (a population of 350,000) and includes an on-site prosthetic manufacturing facility. Using a physiotherapy database at the RGH, we sought to answer the following questions: What are the demographic and clinical characteristics of patients admitted for lower limb prosthetic rehabilitation over 15 years? What are the times to rehabilitation outcomes? How have these changed over 15 years with changes in service delivery? METHODS: This paper is a retrospective observational study using a physiotherapy clinical database (1996 2010) of 531 consecutive individuals with lower limb amputation at one South Australian hospital (RGH). There were two changes in service delivery: 1) a multidisciplinary interim prosthetic programme (IPP) introduced in 1998 and 2) removable rigid dressings (RRDs) introduced in 2000. Outcome measures were patient demographics, clinical characteristics and time to rehabilitation outcome markers. RESULTS: Mean age was 68 years (standard deviation [SD]: 15), with 69% male, 80% dysvascular and 68% transtibial. The overall median inpatient rehabilitation length of stay (RLOS) was 39 days (interquartile range [IQR]: 26 57). Individuals with amputation entering rehabilitation each year had a higher number of co-morbidities (beta: 0.08; 95% confidence interval: 0.05-0.11). Introduction of the IPP was associated with a significant reduction in time to initial prosthetic casting, independent walking and inpatient RLOS. Introduction of RRDs was associated with a significant reduction in time to wound healing, initial prosthetic casting and independent walking. CONCLUSIONS: Individuals with amputation were typically elderly dysvascular men with transtibial amputations. Introduction of the IPP and RRDs successfully reduced time to rehabilitation outcomes including independent walking, an outcome that is rarely reported but is of significance to patients and physiotherapists. PMID- 22674877 TI - Parasite-based screening and proteome profiling reveal orlistat, an FDA-approved drug, as a potential anti Trypanosoma brucei agent. AB - Trypanosoma brucei is a parasite that causes African sleeping sickness in humans and nagana in livestock and is transmitted by the tsetse fly. There is an urgent need for the development of new drugs against African trypanosomiasis due to the lack of vaccines and effective drugs. Orlistat (also called tetrahydrolipstatin or THL) is an FDA-approved antiobesity drug targeting primarily the pancreatic and gastric lipases within the gastrointestinal tract. It shows potential activities against tumors, mycobacteria, and parasites. Herein, we report the synthesis and evaluation of an expanded set of orlistat-like compounds, some of which showed highly potent trypanocidal activities in both the bloodstream form (BSF) and the procyclic form (PCF) of T. brucei. Subsequent in situ parasite based proteome profiling was carried out to elucidate potential cellular targets of the drug in both forms. Some newly identified targets were further validated by the labeling of recombinantly expressed enzymes in Escherichia coli lysates. Bioimaging experiments with a selected compound were carried out to study the cellular uptake of the drug in T. brucei. Results indicated that orlistat is much more efficiently taken up by the BSF than the PCF of T. brucei and has clear effects on the morphology of mitochondria, glycosomes, and the endoplasmic reticulum in both BSF and PCF cells. These results support specific effects of orlistat on these organelles and correlate well with our in situ proteome profiling. Given the economic challenges of de novo drug development for neglected diseases, we hope that our findings will stimulate further research towards the conversion of orlistat-like compounds into new trypanocidal drugs. PMID- 22674876 TI - Enhanced propagation of adult human renal epithelial progenitor cells to improve cell sourcing for tissue-engineered therapeutic devices for renal diseases. AB - Renal cell therapy employing cells derived from adult renal epithelial cell (REC) progenitors promises to reduce the morbidity of patients with renal insufficiency due to acute renal failure and end stage renal disease. To this end, tissue engineered devices addressing the neglected biologic component of renal replacement therapy are being developed. Because human donor tissue is limited, novel enhanced progenitor cell propagation (EP) techniques have been developed and applied to adult human kidney transplant discards from six donors. Changes include more efficient digestion and the amplification of progenitors prior to terminal epithelial differentiation promoted by contact inhibition and the addition of retinoic acid. Differentiated morphology in EP populations was demonstrated by the ability to form polarized epithelium with tight junctions, apical central cilia and expression of brush border membrane enzymes. Evaluation of lipopolysaccharide stimulated interleukin-8 secretion and gamma-glutamyl transpeptisade activity in EP derived cells was used to confirm therapeutic equivalence to REC obtained using published techniques, which have previously shown efficacy in large animal models and clinical trials. Yield exceeded 10(16) cells/gram cortex from the only kidney obtained due to an anatomical defect, while the average yield from diseased kidneys ranged from 1.1 * 10(9) to 8.8 * 10(11) cells/gram cortex, representing an increase of more than 10 doublings over standard methods. Application of the EP protocol to REC expansion has solved the problem of cell sourcing as the limiting factor to the manufacture of cell based therapies targeting renal diseases and may provide a method for autologous device fabrication from core kidney biopsies. PMID- 22674878 TI - Oxidized dextran as crosslinker for chitosan cryogel scaffolds and formation of polyelectrolyte complexes between chitosan and gelatin. AB - Macroporous scaffolds composed of chitosan and using oxidized dextran as a crosslinker are produced through cryogelation. Introducing gelatin as a third component into the structure results in the formation of mesopores in the pore walls, which are not seen if gelatin is excluded. The mesoporous structure is explained by the formation of polyelectrolyte complexes between chitosan and gelatin before crosslinking takes place. The scaffolds exhibit highly elastic properties withstanding compressions up to 60%. The in vitro biocompatibility of the cryogels is evaluated using fibroblasts from a mouse cell line (L929) and it is seen that the cells adhere and proliferate on the scaffolds. The mesoporous structure seems to have a positive effect on proliferation. PMID- 22674879 TI - Molecular imaging of p53 signal pathway in lung cancer cell cycle arrest induced by cisplatin. AB - Cisplatin is a commonly employed chemotherapy drug for lung malignancy. However its efficacy is limited by acquired drug resistance and lacking of an in vivo real-time monitoring approach. The aim of this study is to investigate the effect of cisplatin on lung adenocarcinoma cell line p53-RE-Fluc/A549 in vivo via non invasive reporter gene by molecular imaging. For this study, we employed p53-RE Fluc/A549 cells that overexpressed a vector with three tandem repeats of p53 response element followed by the luciferase reporter gene. P53 activity was evaluated by optical imaging and verified by Western blot after cells were exposed to 10 uM cisplatin for 72 h. The cell cycle was mainly blocked at the S- and G2/M-phases after cisplatin treatment, whereas no significant change was observed in cell apoptotic index. Increased expression of p21 and Bcl-2 as well as decreased expression of Bax were observed after cisplatin treatment by Western blotting. Longitudinal in vivo bioluminescent imaging (BLI) revealed that the p53 activity was increased from 24 to 48 h after transient cisplatin treatment in p53 RE-Fluc/A549-bearing nude mice. RNA sequencing further revealed that cell cycle and p53 signaling pathway genes, such as E2F1, CCNA2, CDK1, and CCNE2 were significantly downregulated after long-term cisplatin treatment. Thus, our study showed that cisplatin exerts its cytotoxic effect through blockage of the cell cycle and may be partly regulated by the p53 signaling pathway. Furthermore, molecular imaging is a useful tool to investigate the mechanism and evaluate the effect of chemotherapy drugs both in vivo and in vitro. PMID- 22674880 TI - Structure-activity relationships of eugenol derivatives against Aedes aegypti (Diptera: Culicidae) larvae. AB - BACKGROUND: Dengue fever is a severe public health problem for several countries. In order to find effective larvicides to aid control programs, the structure activity relationships of eugenol derivatives against Aedes aegypti (Diptera: Culicidae) larvae were evaluated. Additionally, the composition and larvicidal activity of Syzygium aromaticum essential oil was assessed. RESULTS: Four compounds representing 99.05% of S. aromaticum essential oil have been identified. The essential oil was active against Ae. aegypti larvae (LC(50) = 62.3 and 77.0 ppm, field-collected and Rockefeller larvae respectively). The larvicidal activity of eugenol, the major compound of the essential oil, was further evaluated (LC(50) = 93.3 and 71.9 ppm, field-collected and Rockefeller larvae respectively). The larvicidal activity and structure-activity relationships of synthetic derivatives of eugenol were also assessed. The larvicidal activity of the derivatives varied between 62.3 and 1614.9 ppm. Oxidation of eugenol allylic bond to a primary alcohol and removal of the phenolic proton resulted in decreased potency. However, oxidation of the same double bond in 1-benzoate-2-methoxy-4-(2-propen-1-yl)-phenol resulted in increased potency. CONCLUSION: Structural characteristics were identified that may contribute to the understanding of the larvicidal activity of phenylpropanoids. The present approach may help future work in the search for larvicidal compounds. PMID- 22674881 TI - Total synthesis of neurymenolide A based on a gold-catalyzed synthesis of 4 hydroxy-2-pyrones. AB - Treat me gently: for a selective synthesis of the unusually sensitive cyclophanic alpha-pyrone neurymenolide A, the chosen catalysts must be able to distinguish between six different sites of unsaturation, without scrambling any of the skipped pi systems. This challenge was met with a new gold-catalyzed pyrone synthesis in combination with a molybdenum-catalyzed ring-closing alkyne metathesis. PMID- 22674883 TI - Tocilizumab for the treatment of large-vessel vasculitis (giant cell arteritis, Takayasu arteritis) and polymyalgia rheumatica. AB - OBJECTIVE: The interleukin-6 pathway is up-regulated in giant cell arteritis (GCA), Takayasu arteritis (TA), and polymyalgia rheumatica (PMR). We retrospectively assessed the outcomes of 10 patients with relapsing/refractory GCA, TA, or PMR treated with tocilizumab (TCZ). METHODS: Patients with GCA (n = 7), TA (n = 2), and PMR (n = 1) received TCZ. Seven subjects had failed at least 1 second-line agent. The outcomes evaluated were symptoms of disease activity, inflammatory markers, ability to taper glucocorticoids, and cross-sectional imaging when indicated clinically. RESULTS: The mean followup time of this cohort since diagnosis was 27 months (range 16-60 months). The patients were treated with TCZ for a mean period of 7.8 months (range 4-12 months). Before TCZ therapy, the patients experienced an average of 2.4 flares/year. All patients entered and maintained clinical remission during TCZ therapy. The mean daily prednisone dosages before and after TCZ initiation were 20.8 mg/day (range 7-34.3 mg/day) and 4.1 mg/day (range 0-10.7 mg/day), respectively (P = 0.0001). The mean erythrocyte sedimentation rate declined from 41.5 mm/hour (range 11-68 mm/hour) to 7 mm/hour (range 2.2-11.3 mm/hour; P = 0.0001). The adverse effects of TCZ included mild neutropenia (n = 4) and transaminitis (n = 4). One patient flared 2 months after TCZ discontinuation. An autopsy on 1 patient who died from a postoperative myocardial infarction following elective surgery revealed persistent vasculitis of large and medium-sized arteries. CONCLUSION: TCZ therapy led to clinical and serologic improvement in patients with refractory/relapsing GCA, TA, or PMR. The demonstration of persistent large-vessel vasculitis at autopsy of 1 patient who had shown a substantial response requires close scrutiny in larger studies. PMID- 22674882 TI - Effect of chromium dinicocysteinate supplementation on circulating levels of insulin, TNF-alpha, oxidative stress, and insulin resistance in type 2 diabetic subjects: randomized, double-blind, placebo-controlled study. AB - SCOPE: Chromium and cysteine supplementation have been shown to improve glucose metabolism in animal studies. This study examined the hypothesis that chromium dinicocysteinate (CDNC), a complex of chromium and l-cysteine, is beneficial in lowering oxidative stress, vascular inflammation, and glycemia in type 2 diabetic subjects. METHODS AND RESULTS: Type 2 diabetic subjects enrolled in this study were given placebo for 1 month for stabilization and then randomized into one of three groups: placebo (P), chromium picolinate (CP), or CDNC, after which they received daily oral supplementation for 3 months. Of the 100 patients enrolled in the study, 74 patients completed it. There were 25 patients in the P supplemented group, 25 in the CP supplemented and 24 in the CDNC supplemented group who completed the study. Blood markers of glycemia, vascular inflammation, HOMA insulin resistance, and oxidative stress were determined at randomization and after 3 months of supplementation with P, CP, or CDNC. There was a significant decrease at 3 months in insulin resistance (p = 0.02) and in the levels of protein oxidation (p = 0.02) and TNF-alpha (p = 0.01) in the CDNC supplemented cohort compared to baseline. However, there was no statistically significant change in these markers in the CP supplemented group compared to baseline. Insulin levels significantly decreased (p = 0.01) for subjects receiving CDNC but not CP. There was no significant impact of supplementation on HbA(1c) or glucose levels in either of the groups. CONCLUSION: CDNC supplementation lowers insulin resistance by reducing blood levels of TNF-alpha, insulin, and oxidative stress in type 2 diabetic subjects. Therefore, CDNC supplementation has potential as an adjunct therapy for individuals with type 2 diabetes. PMID- 22674884 TI - Identification and characterization of the vitellogenin receptor in Macrobrachium rosenbergii and its expression during vitellogenesis. AB - In oviparous organisms, oocyte maturation depends on massive production of the egg yolk-precursor protein, vitellogenin (Vg). Vg is taken up by the developing oocytes through receptor-mediated endocytosis (RME), a process essential to successful reproduction. The aims of this study were to identify and characterize the yet-unknown vitellogenin receptor (VgR) from the pleocyamate crustacean Macrobrachium rosenbergii, and to investigate its expression levels during vitellogenesis and its interaction with Vg. The VgR gene was cloned, and its translated protein was specifically located at the oocyte membrane. Moreover, for the first time, a VgR protein was identified and sequenced by mass spectrometry. The putative MrVgR displayed high sequence similarity to VgRs from crustaceans, insects, and vertebrates, and its structure includes typical elements, such as an extracellular, lipoprotein-binding domain (LBD), EGF-like, and O-glycosylation domains, a transmembrane domain, and a short, C-terminal, cytosolic tail. In this article, we identify the first crustacean VgR protein, and present data demonstrating its high affinity for a Vg column followed by elution with suramin and EDTA. Additionally we demonstrate that VgR expression in the oocyte is elevated during vitellogenesis. Our results contribute to the fundamental understanding of oocyte maturation in crustaceans, and particularly elucidate Vg uptake through RME via the VgR. PMID- 22674887 TI - Composition and biological activity of essential oils against Metopolophium dirhodum (Hemiptera: Aphididae) cereal crop pest. AB - BACKGROUND: Natural pesticides based on plant essential oils may represent alternative crop protectants. This study analysed the chemical constituents and bioactivities of essential oils from Schinus areira L., Rosmarinus officinalis L. and Tagetes terniflora Kunth against winged and wingless adults of Metopolophium dirhodum (Walk.). RESULTS: The major component of S. areira was alpha phellandrene, that of R. officinalis was 1,8-cineole and that of T. terniflora was cis-ocimene. Rosemary essential oil was more effective than the others in immersion method tests. In contact toxicity, the rosemary oil was the most toxic to wingless adults and the S. areira leaf oil was the most toxic to winged adults. All the EOs produced some degrees of repellency in adults and effects on the reproduction and demographic parameters. CONCLUSION: These results showed that the essential oils from S. areira, R. officinalis and T. terniflora could be used as an alternative in the management of M. dirhodum. PMID- 22674886 TI - Effect of basic fibroblast growth factor in mouse embryonic stem cell culture and osteogenic differentiation. AB - Embryonic stem cells are actively explored as a cell source in tissue engineering and regenerative medicine involving bone repair. Basic fibroblast growth factor (bFGF) has been a valuable growth factor to support the culture of human stem cells as well as their osteogenic differentiation, but the influence of bFGF on mouse embryonic stem (mES) cells is not known. Towards this goal, D3 cells were treated with bFGF during maintenance conditions and during spontaneous and osteogenic differentiation. In feeder-free monolayers, up to 40 ng/ml of exogenous bFGF did not support self-renewal of mES without LIF during cell expansion. During spontaneous differentiation in high-density cultures, bFGF stimulated cell proliferation under certain conditions but did not influence differentiation, as judged by stage-specific embryonic antigen-1 expression. The addition of bFGF reduced the alkaline phosphatase (ALP) activity associated with osteoblast activity during differentiation induced by osteogenic supplements, although the extent of mineralization was unaffected by bFGF. The bFGF increased the mesenchymal stem cell marker Sca-1 in an mES cell population and led to an enhanced increase in osteocalcin and runx2 expression in combination with BMP-2. These results suggest that bFGF could be utilized to expand the cell population in high-density cultures in addition to enriching the BMP-2 responsiveness of mES cells. PMID- 22674889 TI - Glycan-specific metabolic oligosaccharide engineering of C7-substituted sialic acids. PMID- 22674892 TI - Associations for change in physical and psychological factors and treatment response following exercise in knee osteoarthritis: an exploratory study. AB - OBJECTIVE: Understanding how changes in physical and psychological factors following therapeutic exercise are associated with treatment outcome could have important implications for refining rehabilitation programs for knee osteoarthritis (OA). The objective of this study was to examine the association of changes in these factors with changes in pain and function after an exercise program for people with knee OA. METHODS: In total, 152 people with knee OA completed an exercise program consisting of lower extremity strengthening, stretching, range of motion, balance and agility, and aerobic exercises. The change from baseline to the 2-month followup was calculated for physical and psychological factors, including self-reported knee instability, quadriceps strength, knee and ankle range of motion, lower extremity muscle flexibility, fear of physical activity, anxiety, and depressive symptoms. Treatment response was defined as a minimum of a 20% improvement from baseline in both a numerical knee pain rating scale and the Western Ontario and McMaster Universities Osteoarthritis Index physical function scale. The association of each factor with treatment response was examined with logistic regression mutually adjusted for age, sex, body mass index, radiographic severity, and exercise group. RESULTS: Change in self-reported knee instability (odds ratio [OR] 1.67 [95% confidence interval (95% CI) 1.13-2.47]) and fear of physical activity (OR 0.93 [95% CI 0.88 1.00]) were the only 2 factors that were significantly associated with treatment response after adjustment for covariates. CONCLUSION: Improvement in knee instability and fear of physical activity were associated with increased odds of a positive treatment response following therapeutic exercise in subjects with knee OA. PMID- 22674893 TI - A bifunctional tungstate catalyst for chemical fixation of CO2 at atmospheric pressure. PMID- 22674895 TI - Expression of M6 and M7 lysin in Mytilus edulis is not restricted to sperm, but occurs also in oocytes and somatic tissue of males and females. AB - Sperm proteins of marine sessile invertebrates have been extensively studied to understand the molecular basis of reproductive isolation. Apart from molecules such as bindin of sea urchins or lysin of abalone species, the acrosomal protein M7 lysin of Mytilus edulis has been analyzed. M7 lysin was found to be under positive selection, but mechanisms driving the evolution of this protein are not fully understood. To explore functional aspects, this study investigated the protein expression pattern of M7 and M6 lysin in gametes and somatic tissue of male and female M. edulis. The study employs a previously published monoclonal antibody (G26-AG8) to investigate M6 and M7 lysin protein expression, and explores expression of both genes. It is shown that these proteins and their encoding genes are expressed in gametes and somatic tissue of both sexes. This is in contrast to sea urchin bindin and abalone lysin, in which gene expression is strictly limited to males. Although future studies need to clarify the functional importance of both acrosomal proteins in male and female somatic tissue, new insights into the evolution of sperm proteins in marine sessile invertebrates are possible. This is because proteins with male-specific expression (bindin, lysin) might evolve differently than proteins with expression in both sexes (M6/M7 lysin), and the putative function of both proteins in females opens the possibility that the evolution of M6/M7 lysin is under sexual antagonistic selection, for example, mutations beneficial to the acrosomal function that are less beneficial the function in somatic tissue of females. PMID- 22674894 TI - Igf2 pathway dependency of the Trp53 developmental and tumour phenotypes. AB - Insulin-like growth factor 2 (IGF2) and the transformation related protein 53 (Trp53) are potent regulators of cell growth and metabolism in development and cancer. In vitro evidence suggests several mechanistic pathway interactions. Here, we tested whether loss of function of p53 leads to IGF2 ligand pathway dependency in vivo. Developmental lethality occurred in p53 homozygote null mice that lacked the paternal expressed allele of imprinted Igf2. Further lethality due to post-natal lung haemorrhage occurred in female progeny with Igf2 paternal null allele only if derived from double heterozygote null fathers, and was associated with a specific gene expression signature. Conditional deletion of Igf2(fl/fl) attenuated the rapid tumour onset promoted by homozygous deletion of p53(fl/fl) . Accelerated carcinoma and sarcoma tumour formation in p53(+/-) females with bi-allelic Igf2 expression was associated with reductions in p53 loss of heterozygosity and apoptosis. Igf2 genetic dependency of the p53 null phenotype during development and tumour formation suggests that targeting the IGF2 pathway may be useful in the prevention and treatment of human tumours with a disrupted Trp53 pathway. PMID- 22674896 TI - Formation and characterization of gaseous adducts of carbon dioxide to magnesium, (CO2)MgX- (X=OH, Cl, Br). AB - A good fix: the structure and chemical reactivity of a reduced form of CO(2) bonded to magnesium, XMg(eta(2)-O(2)C)(-), is reported. Upon reaction with water it loses CO, while it adds CH(3) upon reaction with alkyl halides, thereby signifying nucleophilicity of the carbon atom in XMg(eta(2)-O(2)C)(-) in S(N)2 reactions. PMID- 22674897 TI - Racial differences in foot disorders and foot type. AB - OBJECTIVE: To describe racial differences in the frequency of structural foot disorders and pes planus and pes cavus foot types in a large cohort of African American and white men and women ages >=50 years. METHODS: Of 1,695 Johnston County Osteoarthritis Project participants evaluated for foot disorders/types in 2006-2010, 4 with lower extremity amputation were excluded, leaving 1,691 available for analyses (mean age 69 years, mean body mass index [BMI] 31.5 kg/m(2) , 68% women, 31% African American). The most common foot disorders/types were identified using a validated foot examination. Each foot disorder/type was compared by race using logistic regression, controlling for age, BMI, and sex. Effect modification between race (African American versus white) and age, BMI (categorized as >=30 kg/m(2) [obese] or <30 kg/m(2) [nonobese]), sex, and education was examined. RESULTS: Hallux valgus (64%), hammer toes (35%), overlapping toes (34%), and pes planus (23%) were common. Compared to whites, African Americans were almost 3 times more likely to have pes planus and were nearly 5 times less likely to have Tailor's bunions or pes cavus. Among the nonobese, African Americans were more likely than whites to have hallux valgus (adjusted odds ratio [OR(adj) ] 2.01, 95% confidence interval [95% CI] 1.39 2.92), hammer toes (OR(adj) 2.64, 95% CI 1.88-3.70), and overlapping toes (OR(adj) 1.53, 95% CI 1.09-2.13). CONCLUSION: Foot disorders are common among adults ages >=50 years and differ by race. Future research is needed to determine the etiology of foot problems, especially those with racial differences, in order to inform prevention approaches. PMID- 22674898 TI - Germ cell survival in C. elegans and C. remanei is affected when the DEAD box RNA helicases VBH-1 or Cre-VBH-1 are silenced. AB - The Vasa family of proteins comprises several conserved DEAD box RNA helicases important for mRNA regulation whose exact function in the germline is still unknown. In Caenorhabditis elegans, there are six known members of the Vasa family, and all of them are associated with P granules. One of these proteins, VBH-1, is important for oogenesis, spermatogenesis, embryo development, and the oocyte/sperm switch in this nematode. We decided to extend our previous work in C. elegans to sibling species Caenorhabditis remanei to understand what is the function of the VBH-1 homolog in this gonochoristic species. We found that Cre VBH-1 is present in the cytoplasm of germ cells and it remains associated with P granules throughout the life cycle of C. remanei. Several aspects between VBH-1 and Cre-VBH-1 function are conserved like their role during oogenesis, spermatogenesis, and embryonic development. However, Cre-vbh-1 silencing in C. remanei had a stronger effect on spermatogenesis and spermatid activation than in C. elegans. An unexpected finding was that silencing of vbh-1 in the C. elegans caused a decrease in germ cell apoptosis in the hermaphrodite gonad, while silencing of Cre-vbh-1 in C. remanei elicited germ cell apoptosis in the male gonad. These data suggest that VBH-1 might play a role in germ cell survival in both species albeit it appears to have an opposite role in each one. PMID- 22674899 TI - Small-sized carbon nanohorns enabling cellular uptake control. AB - Carbon nanotubes perform well in preclinical tests for drug delivery and diagnostic imaging, but controlling the size at less than 100 nm to avoid nonspecific uptake by reticuloendothelial systems while targeting delivery to cells of interest via receptor-mediated endocytosis is difficult, which currently limits their widespread use. Herein, 20-50-nm graphene tubules, small-sized single-walled carbon nanohorns (S-SWNHs), are obtained with a yield of 20% or higher by an oxidative exfoliation of 100 nm pristine SWNH aggregates. S-SWNHs are highly hydrophilic and remarkably resistant to cellular uptake by macrophages (RAW 264.7 cells), tumor cells (HeLa or KB), or normal cells (FHs 173We). The nonstimulatory property to cell membranes therefore makes cellular uptake control of S-SWNHs by functionalization easy. By attaching phospholipid polyethylene glycol, the cellular internalization of S-SWNHs is almost completely inhibited in RAW 264.7 macrophages. When functionalized with tumor-targeting folic acid (FA), FA-S-SWNHs are taken up by FA receptor-overexpressing KB cells but not by normal human embryonic cells (FHs 173We), which do not express the FA receptor. With a high rate of stealth and targeting in vitro, S-SWNHs are one of the most promising nanoparticles for medical use. PMID- 22674900 TI - From in vitro to in vivo--biofuel cells are maturing. PMID- 22674901 TI - Developmental expression of the cellular prion protein (PrP(C) ) in bovine embryos. AB - The mammalian cellular prion protein (PrP(C) ) is a highly conserved glycoprotein that may undergo conversion into a conformationally altered isoform (scrapie prion protein or PrP(Sc) ), widely believed to be the pathogenic agent of transmissible spongiform encephalopathies (TSEs). Although much is known about PrP(Sc) conversion and its role in TSEs, the normal function of PrP(C) has not been elucidated. In adult mammals, PrP(C) is most abundant in the central nervous tissue, with intermediate levels in the intestine and heart, and lower levels in the pancreas and liver. PrP(C) is expressed during neurogenesis throughout development, and it has recently been proposed that PrP(C) participates in neural cell differentiation during embryogenesis. In order to establish the developmental timing and to address the cell-specific expression of PrP(C) during mammalian development, we examined PrP(C) expression in bovine gametes and embryos through gestation Day 39. Our data revealed differential levels of Prnp mRNA at Days 4 and 18 in pre-attachment embryos. PrP(C) was detected in the developing central and peripheral nervous systems in Day-27, 32-, and -39 embryos. PrP(C) was particularly expressed in differentiated neural cells located in the marginal regions of the central nervous system, but was absent from mitotically active, periventricular areas. Moreover, a PrP(C) cell-specific pattern of expression was detected in non-nervous tissues, including liver and mesonephros, during these stages. The potential participation of PrP(C) in neural cell differentiation is supported by its specific expression in differentiated states of neurogenesis. PMID- 22674902 TI - Monitoring ceramic hydroxyapatite media degradation using dynamic image analysis and uniaxial confined bulk compression. AB - Ceramic hydroxyapatite (CHT) is a multimodal chromatographic medium widely used in the pharmaceutical industry for the purification of biomolecules. CHT is a sintered form of hydroxyapatite crystals with moderate stability at acidic conditions. This moderate stability may lead to underperformance of CHT packed bed lifetime, especially under acidic conditions, which should be monitored by diagnostic tools to design optimal buffer systems for the step. This study presents the application of dynamic image analysis (DIA) and uniaxial confined bulk compression (UCBC) to monitor CHT particle degradation as a function of buffer composition. DIA was used to evaluate changes in solidity and morphology, while UCBC was used to evaluate changes in resistance to uniaxial compression. All properties were studied as a function of bed position and operational parameters. Results show that when CHT is exposed to acidic pH, adding phosphate and/or calcium at concentrations of 1 mM minimizes changes in particle solidity and mechanical strength. Changes in CHT morphological properties (i.e., convexity, aspect ratio) are also affected by the presence of calcium and/or phosphate in the inlet buffers. Furthermore, calcium and phosphate have a positive effect on the mechanical behavior of CHT, which is related to changes in the CHT particle solidity. PMID- 22674903 TI - Nuclear spin conversion to probe the methyl rotation effect on hydrogen-bond and vibrational dynamics. AB - A noteworthy example of a molecule with coupled large-amplitude motions is provided by acetylacetone (methyl group torsions and intramolecular hydrogen bonds). The molecule was trapped in solid parahydrogen to investigate the complex proton tunneling processes. Nuclear spin conversion in methyl groups is observed and, combined with IR spectra, documents the coupling between high frequency modes and large amplitude motions. PMID- 22674905 TI - Etiologies, risk factors, and outcomes of bacterial pneumonia after living donor liver transplantation. AB - The prevalence and clinical characteristics of bacterial pneumonia after living donor liver transplantation (LDLT) have not yet been elucidated. We performed a retrospective analysis of 346 LDLT recipients. Fifty patients (14.5%) experienced bacterial pneumonia after LDLT, and they had a higher short-term mortality rate (42.0%) than patients with other types of bacterial infections after LDLT. Gram negative bacteria accounted for 84.0% of the causative pathogens. A multivariate analysis showed that preoperative diabetes (P < 0.01), United Network for Organ Sharing status 1 or 2A (P < 0.01), and an operative blood loss > 10 L (P = 0.03) were significant risk factors for bacterial pneumonia after LDLT. Post-LDLT pneumonia was associated with the following post-LDLT events: the prolonged use of mechanical ventilation (>=3 days), a prolonged stay in the intensive care unit (>=7 days), the creation of a tracheostomy, primary graft dysfunction, the use of mycophenolate mofetil, and the need for renal replacement therapy. Among patients with bacterial pneumonia, the mortality rate was higher for patients with delayed onset pneumonia, which occurred at least 10 days after transplantation (n = 15), and it was significantly associated with graft dysfunction. A combination of broad-spectrum antibiotics and aminoglycosides provided cover for most gram negative bacteria except Stenotrophomonas maltophilia, which was associated with a longer period of mechanical ventilation and was resistant to commonly used broad-spectrum antibiotics. Delayed-onset bacterial pneumonia is a serious type of bacterial infection after LDLT and is frequently associated with graft dysfunction. The multidrug resistance of S. maltophilia is an issue that needs to be addressed. PMID- 22674904 TI - Differential distribution patterns from medial prefrontal cortex and dorsal raphe to the locus coeruleus in rats. AB - Locus coeruleus (LC) consists of a densely packed nuclear core and a surrounding plexus of dendritic zone, which is further divided into several subregions. Whereas many limbic-related structures topographically target specific subregions of the LC, the precise projections from two limbic areas, that is, medial prefrontal cortex (mPFC) and dorsal raphe (DR), have not been investigated. The goal of the present study is to identify and compare the distribution patterns of mPFC and DR afferent terminals to the LC nuclear core as opposed to specific pericoerulear dendritic regions (Peri-LC). To address these issues, anterograde tracer injections were combined with dopamine-beta-hydroxylase (DBH) immunofluorescent staining to reveal the distribution patterns around the LC nuclear complex. Our data suggest that both mPFC-LC and DR-LC projections exhibit selective afferent terminal patterns. More specifically, mPFC-LC projecting fibers mainly target the rostromedial Peri-LC, whereas DR-LC projecting fibers demonstrate a preference to the caudal juxtaependymal Peri-LC. Thus, our present findings provide further evidences that afferents to the LC are topographically organized. Understanding the relationship among different inputs to the LC may help to elucidate the organizing principle which likely governs the interactions between the broad afferent sources of the LC and its global efferent targets. PMID- 22674906 TI - Extraordinary physical properties of functionalized graphene. AB - Graphene has attracted much attention in recent years due to its extraordinary electronic, optical, magnetic, thermal, and mechanical properties. Despite continuing theoretical and experimental success, the unique physical properties of graphene remain underused and underappreciated. The key challenge in harnessing of the unique properties of graphene is the difficulty of reliable manipulation of well-dispersed graphene. Chemical and physical functionalization of graphene has become a focus of especial interest, because they can not only stabilize, but also induce new properties of graphene. This review summarizes the intriguing physical properties of chemically oxidized and noncovalently modified graphene, and graphene-based nanocomposites with polymer matrices or nanoparticles. Along with introducing the physical properties of functionalized graphene, their potential applications in diverse research areas are discussed. PMID- 22674908 TI - Oviductal fluid modulates the dynamics of tyrosine phosphorylation in cryopreserved boar spermatozoa during capacitation. AB - Following insemination, spermatozoa are retained in the utero-tubal junction and isthmic region of the oviduct, where essential steps of capacitation are coordinated. Although a majority of the spermatozoa is exposed to similar conditions in the oviduct, the speed of the response varies depending on the individual male and the state of the spermatozoa. The present study evaluated individual boar variations in terms of the ability of spermatozoa to undergo tyrosine phosphorylation in response to isthmic oviductal fluid (ODF). Cryopreserved spermatozoa from four boars were incubated with pre- and post ovulatory ODF for 6 hr. Sperm kinematics, global protein tyrosine phosphorylation, and dynamics of different phosphorylation patterns were analyzed at hourly interval. The percentage of phosphorylated spermatozoa in the pre ovulatory ODF-treated group was significantly (P < 0.001) higher than in the other treatment groups. Motility, velocity, and protein tyrosine phosphorylation in spermatozoa in response to ODF and control media also showed differences between boars. Spermatozoa from all four boars showed strong expression of a 19 kDa phosphoprotein while spermatozoa from two boars showed additionally strong expression of a 32-kDa phosphoprotein when incubated with pre-ovulatory ODF. While phosphorylation of proteins in the acrosome and the equatorial segment of the sperm were noticed at an early stage during incubation with ODF, tail phosphorylation appeared at a later stage of capacitation. The results indicate individual variation between boars in terms of sperm proteins, including different phosphorylation patterns, in response to ODF, which might be related to fertility. PMID- 22674907 TI - Comparison of children with onset of juvenile dermatomyositis symptoms before or after their fifth birthday in a UK and Ireland juvenile dermatomyositis cohort study. AB - OBJECTIVE: To compare 2 groups of children with juvenile dermatomyositis (DM), those with onset of symptoms before their fifth birthday versus those whose disease begins either on or after their fifth birthday, and to assess whether age at onset is associated with differences in disease presentation, treatments received, or outcomes 2 years after diagnosis. METHODS: Data were analyzed on children recruited to a UK juvenile DM cohort study with a diagnosis of probable or definite juvenile DM and less than 12 months between diagnosis and recruitment. RESULTS: Fifty-five (35%) of 157 children had onset of symptoms before their fifth birthday. At diagnosis, cutaneous ulceration was found in 32.7% of the younger group versus 11.8% of the older group (P = 0.003). Facial or body swelling was reported more often in the younger group, whereas headaches, alopecia, and Raynaud's phenomenon were all more frequently reported in the older group. At followup 2 years later, there were no important differences in outcomes between the groups. More than 90% of patients in both groups received both methotrexate and steroids. Twenty-three percent of both groups remained on steroids 2 years after diagnosis. CONCLUSION: Our study showed that children with juvenile DM with disease onset at age <5 years are more likely to present with ulcerative skin disease and edema. There were no clinically significant differences in outcomes between the 2 groups. PMID- 22674909 TI - Comparison of three methods of drug delivery in the rat lumbar spinal subarachnoid space. AB - This study aimed to compare three most widely used surgeries for experimental lumbar spinal drug delivery in rats. The comparison consisted of assessing the effects of the surgeries and evaluating the deficits produced by these three methods. Sprague Dawley rats underwent acute needle puncture, chronic catheterization via laminectomy or nonlaminectomized catheterization. Body weight changes were measured, animals' general and neurological conditions were observed after surgeries, and motor function was examined by Rota Rod test both prior to and post surgery. Furthermore, nociceptive tests were performed to assess the animals' nociception; hematoxylin, and eosin staining of lumbar spinal cord tissue was performed to evaluate local inflammation caused by surgeries; and both lidocaine paralysis detection; and toluidine blue dye assay were used to confirm the exact location of the catheter. Both needle puncture and catheterization via laminectomy had relatively low success rate of surgery and induced various neurological signs; more severe motor dysfunction, hyperalgesia, allodynia, and local inflammation. Nonlaminectomized catheterization had a higher success rate of surgery, and induced only mild agitation, slight cerebral spinal fluid leakage, mild sensory and motor abnormalities, and minimum pathology in the lumbar spinal cord. The nonlaminectomized catheterization used in this study induces a phenotype of less detectable effects on the animal's behavior and is well-tolerated compared to the acute needle puncture and laminectomized catheterization that are widely used in the literature. Nonlaminectomized catheterization is a safe, accurate and effective way for lumbar drug delivery in rats. PMID- 22674910 TI - Identification of a 17beta-hydroxysteroid dehydrogenase type 10 steroidal inhibitor: a tool to investigate the role of type 10 in Alzheimer's disease and prostate cancer. PMID- 22674912 TI - Direct medical expenditure associated with rheumatoid arthritis in a nationally representative sample from the medical expenditure panel survey. AB - OBJECTIVE: To quantify the incremental direct medical expenditure associated with rheumatoid arthritis (RA) in the US population from a payer's perspective. METHODS: A probability-weighted sample of adult respondents from the Medical Expenditure Panel Survey (2008) was used to identify a cohort of patients with RA and compared to a control cohort without RA. Annual expenditure outcomes, including total expenditure and subgroups related to pharmacy, office-based visits, emergency department visits, hospital inpatient stays, and residual expenditures were estimated. Differences between the RA and control cohort were adjusted for sociodemographic factors, employment status, insurance coverage, health behavior, and health status using a generalized linear model with log link and gamma distribution. Statistical inferences on difference in expenditures between RA and non-RA controls were based on nonparametric cluster bootstrapping using percentiles. RESULTS: The adjusted average annual total expenditure of the RA cohort in 2008 US dollars (USD) was $13,012 (95% confidence interval [95% CI] $1,737-$47,081), while that of the control cohort was $4,950 (95% CI $567 $17,425). The incremental total expenditure of the RA patients as compared to non RA controls was $2,085 (95% CI $250-$7,822). RA patients also had a significantly higher pharmacy expenditure of $5,825 (95% CI $446-$30,998) that was on average $1,380 (95% CI $94-$7,492) higher as compared to the controls. The summated total incremental expenditure of all RA patients in the US was $22.3 billion (2008 USD). CONCLUSION: RA exerts considerable incremental economic burden on US health care, which is primarily driven by the incremental pharmacy expenditure. PMID- 22674913 TI - Characteristics of pelvic lymph node metastases in prostatic adenocarcinoma: a study of 83 cases. AB - Pelvic lymph node dissection (PLND) is currently the most accurate staging modality for lymph node metastases in prostate adenocarcinoma. There is no consensus on the optimal sampling method of PLND specimens among pathologists. This study analyzed the effectiveness of the submission of entire adipose tissue in 451 cases and its impact on total lymph node yield and detection of positive lymph nodes. The sizes of metastatic foci and positive lymph nodes in 83 cases were also studied. Submission of entire adipose tissue increased the lymph node yield and positive lymph node detection by 36.7 % and 1.99 %, respectively. Three cases had positive lymph nodes exclusively in adipose tissue. Of the patients examined, 68% had the largest positive lymph node, <1 cm. In conclusion, it was noted that metastases from prostate cancer were frequently small and seen within small lymph nodes. Submission of entire adipose tissue substantially increased the lymph node yield, but its impact on the detection of additional positive lymph nodes was low. Submission of the entire adipose tissue may be considered as an option in patients with high-risk factors for lymph node metastases. PMID- 22674914 TI - Pulmonary oligometastases: histological features and difficulties in determining site of origin. AB - INTRODUCTION: Pulmonary oligometastases are resected both for diagnostic and therapeutic reasons. The histological features may be nonspecific, resulting in diagnostic difficulties. DESIGN: The authors retrospectively studied the clinical and pathological features of 73 open resections of lung metastases from 64 patients to determine the frequency and types of problems in establishing site of origin. RESULTS: There were 18 primary organ sites, the most frequent being colon (n = 10), head and neck (9 squamous and 6 salivary gland), kidney (n = 7), and soft tissue (n = 7). Unusual histological features included detached alveolar tumor clusters at the periphery (83% of adenocarcinomas), lepidic spread (2 metastatic pancreatic tumors), and entrapped pneumocyte-lined cysts (6 tumors). A majority of squamous carcinomas from the head and neck presented difficulties in regard to excluding a second primary, especially 4 with basaloid features that mimicked primary basaloid lung carcinoma. Other tumors mimicking lung primaries included pancreatic, endometrial, and breast metastases. Germ-cell tumors, sarcomas, melanomas, and sarcomatoid carcinomas presented diagnostic difficulties. Overall, comparison with the primary tumor with or without immunohistochemical studies was performed in 38 of 73 cases (52%). CONCLUSIONS: Pulmonary oligometastases comprise a wide range of histological types and often require careful pathological evaluation to determine primary site of origin. PMID- 22674911 TI - Obesity and other modifiable factors for physical inactivity measured by accelerometer in adults with knee osteoarthritis. AB - OBJECTIVE: To investigate the public health impact of obesity and other modifiable risk factors related to physical inactivity in adults with knee osteoarthritis (OA). METHODS: The frequency of inactivity as defined by the US Department of Health and Human Services was assessed from objective accelerometer monitoring of 1,089 participants (ages 49-84 years) with radiographic knee OA during the Osteoarthritis Initiative 48-month visit (2008-2010). The relationship between modifiable factors (weight status, dietary fat, fiber, smoking, depressive symptoms, knee function, knee pain, and knee confidence) with inactivity was assessed using odds ratios (ORs) and attributable fractions (AFs), controlling for descriptive factors (age, sex, race, education, lives alone, employment, frequent knee symptoms, and comorbidity). RESULTS: Almost half (48.9%) of participants with knee OA were inactive. Being overweight (OR 1.8, 95% confidence interval [95% CI] 1.2-2.5) or obese (OR 3.9, 95% CI 2.6-5.7), having inadequate dietary fiber intake (OR 1.6, 95% CI 1.2-2.2), severe knee dysfunction (OR 1.9, 95% CI 1.3-2.8), and severe pain (OR 1.7, 95% CI 1.1-2.5) were significantly related to inactivity, controlling for descriptive factors. Modifiable factors with significant average AFs were being overweight or obese (AF 23.8%, 95% CI 10.5-38.6%) and inadequate dietary fiber (AF 12.1%, 95% CI 0.1 24.5%), controlling for all factors. CONCLUSION: Being obese or overweight, the quality of the diet, severe pain, and severe dysfunction are significantly associated with physical inactivity in adults with knee OA. All components should be considered in designing physical activity interventions that target arthritis populations with low activity levels. PMID- 22674915 TI - Unmasked: when a clinically malignant disease turns out infectious. A rare case of tularemia. AB - This article reports on a 62-year-old man, who presented with cervical mass and rather nonspecific symptoms. The medical history and clinical workup initially favored a malignant disease such as a carcinoma of unknown primary as the underlying cause. Eventually, the patient was diagnosed with a granulomatous lymphadenitis caused by Francisella tularensis subsp holarctica. Tularemia is a rare disease in Western Europe and can present in multiple ways encompassing almost asymptomatic infections and fatal disease. A rapid diagnosis is often hampered by nonspecific symptoms and the generally low prevalence and incidence of this disease in endemic countries. This case report also provides a comprehensive review of the literature on cervical tularemia and discusses the differential diagnoses. PMID- 22674916 TI - Dedifferentiated liposarcoma with lipoma-like well-differentiated liposarcoma: clinicopathological study of 30 cases, with particular attention to the comingling pattern of well- and dedifferentiated components: a proposal for regrouping of the present subclassification of well-differentiated liposarcoma and dedifferentiated liposarcoma. AB - Dedifferentiated liposarcoma (DDL) is defined as nonlipogenic sarcoma, with an abrupt transition from coexisting well-differentiated liposarcoma (WDL). However, intermingled transition in a mosaic pattern between WDL and DDL is not infrequently encountered. Here, the authors review clinicopathological features of 30 cases of DDL associated with lipoma-like WDL. Histological examination revealed 20 tumors that showed an abrupt transition between WDL and DDL. Among these, 13 tumors showed high-grade spindle-cell sarcoma having histological features of unclassified malignant fibrous histiocytoma (MFH)-like sarcoma (high grade DDL [HDDL]). The remaining 7 tumors showed moderate cellular spindle-cell proliferation with mild nuclear atypia and scant mitotic figures (low-grade DDL [LDDL]). The other 10 tumors showed intermingled transition between WDL and DDL. The interface between these 2 components overlapped, resulting in frequent occurrence of a lipogenic spindle-cell component (comingling DDL). Based on the cellularity and nuclear atypia of the spindle-cell components, there were 7 comingling HDDLs and 3 comingling LDDLs. The histology of comingling LDDL simulated an admixture of spindle-cell liposarcoma and LDDL, and distinction from each other was practically difficult. The histology of comingling HDDL simulated pleomorphic liposarcoma. Follow-up data, available for 23 patients (median, 39 months), showed that 2 patients died of tumor (both had HDDL), and 1 patient died of unrelated disease; 8 patients were alive with recurrent or metastatic diseases (3 HDDLs, 3 LDDLs, and 2 comingling HDDLs). Statistical analysis by Fisher's exact test showed no correlation between histological subtypes (HDDL and LDDL, and typical DDL and comingling DDL). PMID- 22674917 TI - Rheumatoid nodule of the vocal cord. PMID- 22674918 TI - Significance of incidentally detected thyroid tissue in lymph nodes of neck dissections in patients with head and neck carcinoma. AB - BACKGROUND: The incidental discovery of thyroid tissue in lymph nodes of neck dissections performed for a separate primary head and neck cancer is an unusual clinical entity. Careful screening of large number of lymph nodes in the neck dissection specimens by the pathologist is critical in picking up such cases. There is controversy regarding clinical significance of such incidentally detected thyroid tissue in cervical nodes as to whether these represent benign inclusions or whether they represent metastatic focus of an underlying thyroid cancer. The appropriate clinical approach in such cases is less clear because it occurs in the context of another malignancy, usually squamous cell carcinomas with a more aggressive potential. MATERIALS AND METHODS: On reviewing the records of 1602 neck dissections done in patients with head and neck cancers over the years 2007-2011, this study identified 5 patients with incidentally detected thyroid tissue with features of malignancy in cervical lymph nodes. Subsequent thyroidectomies done in 4 cases showed primary thyroid cancer. CONCLUSION: The study's results emphasize the need for the clinician to do an accurate reevaluation and follow-up of patients with incidental occult metastasis for detection of primary thyroid tumor. A thorough sampling and screening of lymph nodes in neck dissection specimens by the pathologist is also essential. Incidentally discovered thyroid tissue in cervical lymph nodes need not always be benign inclusions. Aggressive therapy, however, may not be needed in all cases. PMID- 22674919 TI - Human papillomavirus type 16 DNA detected in pulmonary metastases from a penile squamous cell carcinoma: a case study. AB - This report describe the case of a patient presenting with pulmonary metastases from a penile cancer, where the presence of the human papillomavirus (HPV) type 16 DNA both in the primary tumor and in the distant metastases confirmed the spreading of the disease, ruling out a possible primary lung squamous cell carcinoma. Indeed, according to the findings, the HPV genotyping test might help in the identification of metastatic disease from anogenital malignancies or other HPV-related cancers. PMID- 22674920 TI - Clinical and cost effectiveness of booklet based vestibular rehabilitation for chronic dizziness in primary care: single blind, parallel group, pragmatic, randomised controlled trial. AB - OBJECTIVE: To determine the clinical and cost effectiveness of booklet based vestibular rehabilitation with and without telephone support for chronic dizziness, compared with routine care. DESIGN: Single blind, parallel group, pragmatic, randomised controlled trial. SETTING: 35 general practices across southern England between October 2008 and January 2011. PARTICIPANTS: Patients aged 18 years or over with chronic dizziness (mean duration >five years) not attributable to non-vestibular causes (confirmed by general practitioner) and that could be aggravated by head movement (confirmed by patient). INTERVENTIONS: Participants randomly allocated to receive routine medical care, booklet based vestibular rehabilitation only, or booklet based vestibular rehabilitation with telephone support. For the booklet approach, participants received self management booklets providing comprehensive advice on undertaking vestibular rehabilitation exercises at home daily for up to 12 weeks and using cognitive behavioural techniques to promote positive beliefs and treatment adherence. Participants receiving telephone support were offered up to three brief sessions of structured support from a vestibular therapist. MAIN OUTCOME MEASURES: Vertigo symptom scale-short form and total healthcare costs related to dizziness per quality adjusted life year (QALY). RESULTS: Of 337 randomised participants, 276 (82%) completed all clinical measures at the primary endpoint, 12 weeks, and 263 (78%) at one year follow-up. We analysed clinical effectiveness by intention to treat, using analysis of covariance to compare groups after intervention, controlling for baseline symptom scores. At 12 weeks, scores on the vertigo symptom scale in the telephone support group did not differ significantly from those in the routine care group (adjusted mean difference -1.79 (95% confidence interval -3.69 to 0.11), P=0.064). At one year, both intervention groups improved significantly relative to routine care (telephone support -2.52 (-4.52 to -0.51), P=0.014; booklet only -2.43 (-4.27 to -0.60), P=0.010). Analysis of cost effectiveness acceptability curves showed that both interventions were highly cost effective; at very low QALY values, the booklet only approach was most likely to be cost effective, but the approach with additional telephone support was most likely to be cost effective at QALY values more than L1200 (?1488; $1932). Using the booklet approach with telephone support, five (three to 12) patients would need to be treated for one patient to report subjective improvement at one year. CONCLUSIONS: Booklet based vestibular rehabilitation for chronic dizziness is a simple and cost effective means of improving patient reported outcomes in primary care. TRIAL REGISTRATION: ClinicalTrials.gov NCT00732797. PMID- 22674921 TI - Facilitated physical activity as a treatment for depressed adults: randomised controlled trial. AB - OBJECTIVE: To investigate the effectiveness of facilitated physical activity as an adjunctive treatment for adults with depression presenting in primary care. DESIGN: Pragmatic, multicentre, two arm parallel randomised controlled trial. SETTING: General practices in Bristol and Exeter. PARTICIPANTS: 361 adults aged 18-69 who had recently consulted their general practitioner with symptoms of depression. All those randomised had a diagnosis of an episode of depression as assessed by the clinical interview schedule-revised and a Beck depression inventory score of 14 or more. INTERVENTIONS: In addition to usual care, intervention participants were offered up to three face to face sessions and 10 telephone calls with a trained physical activity facilitator over eight months. The intervention was based on theory and aimed to provide individually tailored support and encouragement to engage in physical activity. MAIN OUTCOME MEASURES: The primary outcome was self reported symptoms of depression, assessed with the Beck depression inventory at four months post-randomisation. Secondary outcomes included use of antidepressants and physical activity at the four, eight, and 12 month follow-up points, and symptoms of depression at eight and 12 month follow up. RESULTS: There was no evidence that participants offered the physical activity intervention reported improvement in mood by the four month follow-up point compared with those in the usual care group; adjusted between group difference in mean Beck depression inventory score -0.54 (95% confidence interval -3.06 to 1.99; P=0.68). Similarly, there was no evidence that the intervention group reported a change in mood by the eight and 12 month follow-up points. Nor was there evidence that the intervention reduced antidepressant use compared with usual care (adjusted odds ratio 0.63, 95% confidence interval 0.19 to 2.06; P=0.44) over the duration of the trial. However, participants allocated to the intervention group reported more physical activity during the follow-up period than those allocated to the usual care group (adjusted odds ratio 2.27, 95% confidence interval 1.32 to 3.89; P=0.003). CONCLUSIONS: The addition of a facilitated physical activity intervention to usual care did not improve depression outcome or reduce use of antidepressants compared with usual care alone. TRIAL REGISTRATION: Current Controlled Trials ISRCTN16900744. PMID- 22674922 TI - Validation of two age dependent D-dimer cut-off values for exclusion of deep vein thrombosis in suspected elderly patients in primary care: retrospective, cross sectional, diagnostic analysis. AB - OBJECTIVE: To determine whether the use of age adapted D-dimer cut-off values can be translated to primary care patients who are suspected of deep vein thrombosis. DESIGN: Retrospective, cross sectional diagnostic study. SETTING: 110 primary care doctors affiliated with three hospitals in the Netherlands. PARTICIPANTS: 1374 consecutive patients (936 (68.1%) aged >50 years) with clinically suspected deep vein thrombosis. MAIN OUTCOME MEASURES: Proportion of patients with D-dimer values below two proposed age adapted cut-off levels (age in years * 10 MUg/L in patients aged >50 years, or 750 MUg/L in patients aged >= 60 years), in whom deep vein thrombosis could be excluded; and the number of false negative results. RESULTS: Using the Wells score, 647 patients had an unlikely clinical probability of deep vein thrombosis. In these patients (at all ages), deep vein thrombosis could be excluded in 309 (47.8%) using the age dependent cut-off value compared with 272 (42.0%) using the conventional cut-off value of 500 MUg/L (increase 5.7%, 95% confidence interval 4.1% to 7.8%). This exclusion rate resulted in 0.5% and 0.3% false negative cases, respectively (increase 0.2%, 0.004% to 8.6%).The increase in exclusion rate by using the age dependent cut-off value was highest in the oldest patients. In patients older than 80 years, deep vein thrombosis could be safely excluded in 22 (35.5%) patients using the age dependent cut-off value compared with 13 (21.0%) using the conventional cut-off value (increase 14.5%, 6.8% to 25.8%). Compared with the age dependent cut-off value, the cut-off value of 750 MUg/L had a similar exclusion rate (307 (47.4%) patients) and false negative rate (0.3%). CONCLUSIONS: Combined with a low clinical probability of deep vein thrombosis, use of the age dependent D-dimer cut-off value for patients older than 50 years or the cut-off value of 750 MUg/L for patients aged 60 years and older resulted in a considerable increase in the proportion of patients in primary care in whom deep vein thrombosis could be safely excluded, compared with the conventional cut-off value of 500 MUg/L. PMID- 22674923 TI - Exercise to treat depression. PMID- 22674924 TI - Kolaviron biflavanoids of Garcinia kola seeds protect atrazine-induced cytotoxicity in primary cultures of rat Leydig cells. AB - We sought to explore the mechanism by which kolaviron (Kol) protects against atrazine (ATZ)-induced toxicity of cultured interstitial Leydig cells (ILCs). In our experiments, treatment with Kol improved Leydig cell viability and significantly reduced malondialdehyde (MDA) and reactive oxygen species (ROS) levels. Further investigations revealed a reduction in glutathione peroxidase (GSH-Px), glutathione reductase (GR), glutathione-S-transferase (GST) and elevation of superoxide dismutase 1 (SOD-1) and superoxide dismutase 2 (SOD-2) as measured by messenger RNA (mRNA) expression. Additionally, the ATZ-induced alterations in the mRNA transcript copy numbers of steroidogenesis genes: steroidogenic acute regulatory protein (StAR), cytochrome P450 side-chain cleavage enzyme (CYP11A1), and 3beta-hydroxysteroid dehydrogenase (3beta-HSD) were shifted toward the control values by Kol. Taken together, these findings indicate that Kol protects ILCs from ATZ-induced toxicity via the reduction in ROS and MDA levels and induce normalization of mRNA levels of all the tested genes. PMID- 22674925 TI - Herpes simplex encephalitis. PMID- 22674926 TI - A painful swollen finger. PMID- 22674927 TI - The management of suspected encephalitis. PMID- 22674928 TI - FDA is to appeal against ban on importing execution drug. PMID- 22674929 TI - A pilot study of rapid benchtop sequencing of Staphylococcus aureus and Clostridium difficile for outbreak detection and surveillance. AB - OBJECTIVES: To investigate the prospects of newly available benchtop sequencers to provide rapid whole-genome data in routine clinical practice. Next-generation sequencing has the potential to resolve uncertainties surrounding the route and timing of person-to-person transmission of healthcare-associated infection, which has been a major impediment to optimal management. DESIGN: The authors used Illumina MiSeq benchtop sequencing to undertake case studies investigating potential outbreaks of methicillin-resistant Staphylococcus aureus (MRSA) and Clostridium difficile. SETTING: Isolates were obtained from potential outbreaks associated with three UK hospitals. PARTICIPANTS: Isolates were sequenced from a cluster of eight MRSA carriers and an associated bacteraemia case in an intensive care unit, another MRSA cluster of six cases and two clusters of C difficile. Additionally, all C difficile isolates from cases over 6 weeks in a single hospital were rapidly sequenced and compared with local strain sequences obtained in the preceding 3 years. MAIN OUTCOME MEASURE: Whole-genome genetic relatedness of the isolates within each epidemiological cluster. RESULTS: Twenty-six MRSA and 15 C difficile isolates were successfully sequenced and analysed within 5 days of culture. Both MRSA clusters were identified as outbreaks, with most sequences in each cluster indistinguishable and all within three single nucleotide variants (SNVs). Epidemiologically unrelated isolates of the same spa-type were genetically distinct (>=21 SNVs). In both C difficile clusters, closely epidemiologically linked cases (in one case sharing the same strain type) were shown to be genetically distinct (>=144 SNVs). A reconstruction applying rapid sequencing in C difficile surveillance provided early outbreak detection and identified previously undetected probable community transmission. CONCLUSIONS: This benchtop sequencing technology is widely generalisable to human bacterial pathogens. The findings provide several good examples of how rapid and precise sequencing could transform identification of transmission of healthcare associated infection and therefore improve hospital infection control and patient outcomes in routine clinical practice. PMID- 22674930 TI - Safety assessment of Bacillus licheniformis Me1 isolated from milk for probiotic application. AB - In this study, an in vivo toxicological safety assessment of Bacillus licheniformis Me1, a native isolate from milk, was performed. An acute toxicity study in male albino Wistar rats demonstrated no treatment-related illness or mortality. A 90-day subchronic oral toxicity study using 2 doses (1.1 * 10(10) and 1.1 * 10(11) colony-forming unit [CFU]/kg body weight [BW], respectively) failed to show dose-dependent illness or mortality. Moreover, neither significant differences in serum biochemical and hematological analyses nor histopathological changes in organs or tissues were found when compared to the control groups. The no-observed-adverse-effect level (NOAEL) was found to be greater than 1.1 * 10(11) CFU/kg BW. The in vivo micronucleus assay in mice did not reveal any signs of genotoxic effect at any of the doses tested. Furthermore, dermal and acute eye irritation tests conducted in rabbits showed no edema or erythema and ocular lesions. These results suggest that B licheniformis Me1 can be considered safe for food industry applications. PMID- 22674931 TI - Malathion/oxon and lead acetate increase gene expression and protein levels of transient receptor potential canonical channel subunits TRPC1 and TRPC4 in rat endothelial cells of the blood-brain barrier. AB - This study examined the effects of malathion and lead on transient receptor potential canonical channel TRPC1/TRPC4 channels in rat brain endothelial cells as a mechanism to explain previously noted blood-brain barrier (BBB) permeability induced by these compounds. Lead, malathion, malaoxon and combinations of these were assessed for protein levels and gene expression of TRPC1/C4 at 2, 4, 8, 16, and 24 hours after exposure. Changes in intracellular free calcium dynamics were also assessed. Compounds increased TRPC1 and TRPC4 protein levels as well as gene expression within 4 hours after exposure. Basal levels of intracellular free calcium were also elevated. Increases in gene and protein expression may be associated with an increase in the numbers of TRP channels, and the increases in intracellular calcium may be associated with activation of such channels. Therefore, upregulation and activation of the TRPC1/TRPC4 may be a mechanism by which these neurotoxicants affect BBB permeability. PMID- 22674932 TI - Human blood and plasma partition coefficients for C4-C8 n-alkanes, isoalkanes, and 1-alkenes. AB - Human blood:air and plasma:air partition coefficients for C(4)-C(8) n-alkanes, isoalkanes, and 1-alkenes were determined using multiple headspace extraction coupled with solid phase microextraction and gas chromatography. Mean blood:air partition coefficients expressed in the form of dimensionless blood-to-air concentration ratio (g/mL(b)/g/mL(a)) were 0.183, 0.416, 1.08, 2.71, and 5.77 for C(4)-C(8) n-alkanes; 0.079, 0.184, 0.473, 1.3, and 3.18 for C(4)-C(8) isoalkanes; and 0.304, 0.589, 1.32, 3.5, and 7.01 for C(4)-C(8) 1-alkenes, respectively (n = 8). The reported partition coefficient values increased exponentially with boiling points, molecular weights, and the carbon atoms in the particle. The solubility of 1-alkenes in blood was higher than in plasma, whereas the blood:air and plasma:air partition coefficients of n-alkanes and isoalkanes did not differ significantly. Consequently, additional interactions of 1-alkenes with whole blood seem to occur. The presented findings are expected to be particularly useful for assessing the uptake, distribution, and elimination of hydrocarbons in human organism. PMID- 22674933 TI - BacMam system for FRET-based cAMP sensor expression in studies of melanocortin MC1 receptor activation. AB - Cyclic adenosine monophosphate (cAMP) is a second messenger of many G-protein coupled receptors (GPCRs) and a useful readout molecule to estimate the biological activity of various GPCR-specific agents. Here we report the development and use of a Forster resonance energy transfer (FRET) biosensor for cAMP (Epac2-camps) combined with a baculovirus-based BacMam transduction system. The constructed BacMam-Epac2-camps viral transduction system is a simple and robust tool for ligand screening at the second-messenger level in a variety of mammalian cell lines. The level of biosensor protein expression can easily be adjusted in a dose-dependent manner depending on the multiplicity of viral infection. For setting up the assay, we used a B16F10 murine melanoma cell line with endogenous expression of melanocortin-1 receptor (MC(1)R). The receptor activation was characterized by a set of MC(1)R full and partial agonists. Bivalent ions Ca(2+) as well as Mg(2+) modulated ligand potencies, whereas the effect was ligand and ion specific. Results obtained for MC(1)R indicate that the BacMam-Epac2-camps system may also be applicable for studying the activation of other GPCRs and may be implemented in routine analysis as well as in high throughput screening. PMID- 22674934 TI - Effect of Reveromycin A on experimental tooth movement in OPG-/- mice. AB - In osteoprotegerin-deficient (OPG-/-) mice, osteoclast activity causes bone resorption to outpace bone formation, leading to the development of severe osteoporosis. Such mice are therefore useful for investigating the alveolar bone of patients with osteoporosis. Reveromycin A (RM-A) was recently identified as the unique agent acting on osteoclast activation. This study aimed to analyze the effect of RM-A on the orthodontic treatment of OPG-/- mice (a model of osteoporosis patients with high levels of bone turnover). We examined alveolar bone remodeling in OPG-/- and wild-type (WT) mice during continuous tooth movement. The orthodontic force was induced by means of a Ni-Ti closed-coil spring to move the maxillary first molar for 14 days. RM-A sodium salt (1 mg/kg) was administered intraperitoneally twice daily. In OPG-/- mice, the tooth movement distance was longer, alveolar bone resorption was enhanced, the osteoclast count was greater, and serum alkaline phosphatase and tartrate resistant acid phosphatase levels were higher relative to those in WT mice. However, the administration of RM-A in OPG-/- mice reduced these parameters. We conclude that RM-A normalizes bone metabolism and loss of alveolar bone during continuous tooth movement in OPG-/- mice. PMID- 22674935 TI - Coiling of a vulvar arterio-venous malformation. AB - The authors report the case of a 13-year-old girl with a painful vulvar swelling and abnormal vaginal bleeding, increasing in size after trauma. With MRI (GE Signa HDx 1.5 Tesla), it is diagnosed as an arterio-venous malformation arising from the left superior femoral artery. It is treated by embolisation using a coil. PMID- 22674936 TI - Bilateral ballism following streptococcal infection, associated with psychiatric disorder and purpura. AB - A woman in her 30s was brought to the hospital with abnormal movements. Three months prior, the patient had exacerbation of the movements after an episode of recurrent pharyngitis. Neurological examination revealed, violent involuntary movement that affected both upper and lower limbs, hypotonia and ataxia. Other findings including emotional instability and involuntary movements were considered ballistic. Throat culture showed beta haemolytic streptococci, tonsillectomy and specific antibiotic improved bilateral ballism and psychiatic disorder. This is the first report of bilateral ballism poststreptococcal infection. PMID- 22674937 TI - Delayed postpartum haemorrhage secondary to a ruptured uterine artery pseudo aneurysm, successfully treated by transarterial embolisation. AB - A 29-year-old woman (gravida 1, para 1) had an uneventful first pregnancy and a delivery by emergency caesarean section at term. The caesarean section was complicated by a massive obstetric haemorrhage of 5000 ml. After closure, an immediate re-laparotomy was indicated due to heavy vaginal bleeding. The site of bleeding was identified as an extension of the uterine incision, and was sutured. She was stabilised by transfusion of blood and blood products in the intensive therapy unit, and discharged 5 days later. The patient was re-admitted 6 weeks later with brisk, painless vaginal bleeding, passing large clots from a well contracted uterus. Her haemoglobin decreased from 11.8 to 7.8 g/dl overnight. In view of her history, an urgent CT angiogram was performed, which revealed the presence of a pseudo-aneurysm arising from the left uterine artery. This was successfully occluded by transarterial embolisation, obviating the need for further surgical exploration. PMID- 22674938 TI - Choledochal-duodenal fistula presenting as an upper GI bleed. AB - Gallstones are common and largely asymptomatic, but can result in significant morbidity in a small proportion of patients. Choledochal-enteric fistulation is one such complication with an associated mortality of 15-18%. The authors present a case of an 88-year-old man admitted to the general medical ward with an acute upper gastrointestinal bleed. Oesophagogastroduodenoscopy found a large gallstone impacted in the pylorus and CT scan revealed a choledochal-duodenal fistula. At laparotomy it was found that a 6.2 cm gallstone had fistulated into D1 and the pylorus and impacted there, causing outflow obstruction - Bouveret's syndrome. A subtotal cholecystectomy was performed and the stone was removed by a separate gastrostomy. A radiological follow through study on day 14 showed contrast passing freely through the duodenum with no leak and the patient went on to make a slow, but uneventful recovery. PMID- 22674939 TI - VGKC positive autoimmune encephalopathy mimicking dementia. AB - Voltage gated potassium channel antibodies (VGKC Abs) are known to cause three rare neurological syndromes- neuromyotonia, Morvan's syndrome and limbic encephalitis although an increasing array of other associated neurological symptoms are becoming recognised. The authors describe the case of a 60-year-old female who presented to the neurology clinic with an apparent early onset dementing process. She was noted to have both extrapyramidal and frontal release signs on examination and was admitted for further evaluation. Her dementia investigation including a neoplastic screen was negative except for VGKC antibody positivity. Her symptoms dramatically improved with commencement of immunosuppression. A non-paraneoplastic VGKC antibody associated dementia-like syndrome has rarely been described. The authors add to the few existing reports of what represents an important reversible cause of cognitive impairment. PMID- 22674940 TI - Chronic inflammatory demyelinating polyradiculoneuropathy complicating anti TNF alpha therapy for chronic plaque psoriasis. AB - A 53-year-old woman with chronic plaque psoriasis treated with adalimumab (antitumour necrosis factor (anti TNF) alpha therapy) for 10 months presented with an 8 week history of hyperesthesia in a 'glove and stocking' distribution and clumsiness on walking. Nerve conduction studies confirmed the clinical diagnosis of a chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). She was admitted and treated with intravenous immunoglobulin and oral steroids and made an excellent recovery. To our knowledge, this is the first published report of CIDP associated with anti TNF alpha therapy given to treat psoriasis. PMID- 22674941 TI - Crossing the other side of the algorithm: a challenging case of adrenal Cushing's syndrome. AB - The diagnosis of endogenous Cushing's syndrome and its aetiology involved documenting the hypercotisolism and then determining whether that hypercortisolism is adrenocorticotropic hormone-dependent (ACTH-dependent) or not. Hence, following the algorithm, an undetected ACTH level points to an adrenal Cushing's while a detectable or elevated ACTH level points to either a pituitary or ectopic Cushing's syndrome. The authors present a case of florid adrenal Cushing's syndrome initially presenting with a normal ACTH level, which led to the investigation for an ACTH-secreting tumour. Adding to the confusion, a MRI done showed an intrasellar focus. Knowledge of how ACTH-dependent (versus ACTH-independent) Cushing's syndrome manifests clinically, supported by results of repeat laboratory tests, led to the true diagnosis. This case illustrates that a detectable ACTH does not rule out an adrenal Cushing's syndrome nor does a positive pituitary imaging confirm Cushing's disease. PMID- 22674942 TI - Complements do not lie. AB - A 74-year-old patient presented with constitutional symptoms and was found to have acute kidney injury. He was known to have a prosthetic aortic valve. He was febrile with splenomegaly and vasculitic lesions on both hands. Nephritic screen revealed strongly positive cytoplasmic-antineutrophil cytoplasmic antibodies (c ANCA). Differential diagnosis thus included a small vessel vasculitis or infective endocarditis. Transoesophageal echocardiography demonstrated no vegetations and serial blood cultures were negative. Immunosuppression for presumed granulomatosis with polyangiitis (Wegeners granulomatosis) was therefore instituted. The patient deteriorated, requiring multi-organ support. Renal biopsy showed a proliferative glomerulopathy and complements were low. Atypical screen for culture negative endocarditis revealed a strongly positive IgG-antibody titre against Bartonella henselae. Immunosuppression was discontinued and treatment for chronic Bartonellosis commenced. The patient made a remarkable recovery. His renal function quickly returned to normal, and ANCA titres and complements normalised. He was discharged home after completing a 6 week course of antibiotic therapy. PMID- 22674943 TI - Bilateral macular haemorrhages secondary to hepatitis-associated aplastic anaemia, treated with Nd:YAG laser posterior hyaloidotomy. AB - Hepatitis-associated aplastic anaemia (HAAA) is an uncommon but distinct variant of aplastic anaemia in which pancytopenia and bone marrow failure appears 2-3 months after an acute attack of hepatitis. Although bilateral vision loss may rarely be the initial presentation of aplastic anaemia, no such report is known in HAAA. Here the authors report such a case presenting with large premacular subhyaloid haemorrhages secondary to severe anaemia and thrombocytopenia. Anaemic hypoxic damage to the vessel wall together with increased cardiac output and low platelet counts are interacting causal factors in the development of bleeding. Though these haemorrhages are benign and usually improve spontaneously, the presence of blood may cause permanent macular changes before it resolves. Posterior hyaloidotomy enabled rapid resolution of premacular subhyaloid haemorrhage thereby restoring vision and preventing need for vitreo-retinal surgery. These patients should be advised to refrain from valsalva manoeuvres, ocular rubbing and vigorous exercise to prevent ocular morbidity. PMID- 22674945 TI - A malignant retroperitoneal mass--a rare presentation of recurrent thymoma. AB - A 60-year-old man presented with a suspected retroperitoneal mass, after primarily resected thymoma (type B1/B2, Masaoke stage 1). A germ cell tumour was excluded and a diagnostic biopsy was performed. The mass appeared to be a local recurrence of the primary thymoma, for example, a droplet metastasis, progressed to type B3. PMID- 22674944 TI - Total pleurectomy as the surgical treatment for recurrent secondary spontaneous pneumothorax in a child with severe pulmonary Langerhans cells histiocytosis. AB - Pulmonary Langerhans cell histiocytosis (LCH) in children is more extensive and is a rare cause of spontaneous secondary pneumothorax (SSP) which tends to be recurrent and refractory to conventional treatment. Its occurrence in paediatric patients posed great challenge to the choice of surgical management. Surgery in the form of pleurodesis is only considered if SSP does not improve after chemotherapy and after considering all relevant risk and benefits of surgery to patients. Chemical pleurodesis will not give the expected effect to eradicate SSP in this patient. Therefore mechanical pleurodesis is the treatment of choice. There are various techniques to perform mechanical pleurodesis; from pleural abrasion to pleurectomy. In the authors' experience, bilateral total pleurectomy provided the best outcome for this 9-year-old patient with persistent respiratory distress from SSP due to extensive pulmonary LCH. PMID- 22674946 TI - Rare case of ER positive colorectal stricture demonstrating improvement with letrozole. AB - The authors present a rare case of a patient with an estrogen receptor (ER) positive malignant colorectal stricture, with no identifiable primary breast carcinoma. There was demonstrated endoscopic and symptomatic improvement after treatment with letrozole. Gastrointestinal metastases from breast cancer usually present with a previous history of breast cancer, however our patient had no prior or current proven history of breast cancer. Biopsy and immunohistochemical staining of the malignant colonic lesion showed an adenocarcinoma with positive ER staining. Mammogram, breast ultrasound and MRI of the breasts were all negative. She was successfully treated with letrozole for 3 years that resulted in endoscopic and symptomatic improvement in her colorectal stricture. PMID- 22674947 TI - Impulse control loss rapidly reversed by aripiprazole in a patient with concomitant bipolar disease type I and posttraumatic frontal lobe lesions. AB - A 45-year-old man with bipolar disease type I and post-traumatic frontal lobe lesions following a previous psychotic episode was hospitalised after having stopped taking aripiprazole (15 mg/day) and lithium (126 mg twice/daily). He presented with hypomania, psychosis, verbal unresponsiveness and disorientation. He engaged in compulsive onanism in public which resulted in the restriction of his freedom, suggesting impulse control disorder (ICD). Electroencephalogram showed no epileptiform activity. Brain CT-scan showed post-traumatic bifrontal and left occipital lesions. Viral and bacterial serologies were normal. Lithium was initially reinstated (same dose), but it was aripiprazole reinstatement at a lower dose (10 mg) that made his condition rapidly improve within 24-36 h. Aripiprazole is a partial dopamine D2-receptor antagonist that blocks dopamine at higher dopamine concentrations and augments/releases prefrontal cortex dopamine at lower concentrations. The rapid recovery suggests stabilisation of dopamine levels in the frontal lobes and that ICD may be modified by aripiprazole treatment. PMID- 22674948 TI - Dysphagia due to thoracic aortic aneurysm, relieved by thoracic endovascular aneurysm repair: a case report and review of the literature. AB - Thoracic aortic aneurysm is a rare clinical entity that is usually asymptomatic. Failure to treat this type of aneurysm can prove fatal. Here, the authors report a case of thoracic aortic aneurysm causing chronically worsening compressive symptoms including dysphagia. This was diagnosed following a suspicious chest radiograph, and confirmed with thoracic CT angiogram. These symptoms remitted over a period of months following thoracic endovascular repair of the aneurysm. Aneurysmal compression and deviation of the oesophagus is noticeably reduced following repair. This is one of few cases in the literature of a remittance of dysphagia following endovascular aneurysm repair, and highlights that rare causes of dysphagia ought not to be disregarded. PMID- 22674949 TI - Getting to the heart of rectal bleeding: subacute bacterial endocarditis presenting as anaemia and a GI bleed. AB - In this case report, the authors demonstrate a case of subacute bacterial endocarditis presenting with anaemia. It is the first of its kind to describe a delay in diagnosis due to an initial patient investigation for a bleed rather than a cardiac evaluation. Astute clinicians need to be aware of the causes of anaemia in patients with endocarditis and consider that in Streptococcus bovis (S bovis) infection can be related to gastrointestinal polyps or malignancy resulting in bleeding. Although patients with S bovis endocarditis should undergo full gastrointestinal investigation after endocarditis is diagnosed, it should not delay medical treatment. In this article, the authors discuss the consequences of failing to achieve timely recognition of endocarditis along with common systemic complications. The authors also outline current recommendations for surgical intervention as heart valve replacement surgery was warranted in the patient to prevent fatal outcome. PMID- 22674950 TI - Memory deficits due to brain injury: unique PET findings and dream alterations. AB - The authors herein report the case of a young male with memory deficits due to a traumatic head injury, who presented with sleep-related symptoms such as hypersomnia and dream alterations. Although MRI and polysomnography showed no abnormalities, (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) and (11)C flumazenil (FMZ)-PET revealed findings consistent with cerebral damage to the affected temporal region. The memory deficit of the patient gradually improved in parallel with the relief of the sleep-related symptoms. FDG-PET showed considerable improvement in glucose metabolism when he had recovered, however, evidence of neural loss remained in the FMZ-PET findings. PMID- 22674951 TI - Congenital infantile myofibroma causing intrauterine death in a twin. AB - While infantile myofibromatosis is the most common mesenchymal tumour of infancy, only around 300 cases have been reported. The authors report a 33-year-old para 1 with an uncomplicated, dichorionic diamniotic twin pregnancy who was diagnosed with an intrauterine death of one twin at 36+5 weeks gestation. At caesarean section, a macerated male stillborn weighing 2.72 kg was delivered. Postmortem examination revealed a pedunculated lesion attached to the left shoulder and underlying muscle consistent with a congenital myofibroma. The cause of death was postulated to be haemorrhage from the tumour surface causing fetal anaemia. PMID- 22674952 TI - Juvenile idiopathic arthritis coexisting with sickle cell disease: two case reports. AB - Two cases of coexisting juvenile idiopathic arthritis (JIA) and sickle cell disease (ages 7 and 17) are presented. The diagnoses of JIA were delayed for years because of the similarity of presentations in the two conditions. Both cases had been treated with non-steroidal anti-inflammatory drugs for years. Both had positive rheumatoid factor, and elevated erythrocyte sedimentation rate (ESR) while one of the patients had elevated serum ferritin and anticyclic citrullinated protein. Radiology showed marked arthritic changes with presence of avascular necrosis in a patient's head of femur. Both cases were treated with etanercept for 6 months each, as well as methotrexate. At the end of 6 months, the joint count for pains and swelling were done as well as ESR. PMID- 22674953 TI - An unusual cause of school refusal. AB - A 6-year-old school boy was brought to the child developmental specialist with complaints of school absenteeism and school refusal behaviour of 7 months duration. Before the onset of school refusal, he had two episodes of unresponsiveness with abnormal posturing preceded by vertigo, which were diagnosed and managed as epileptic seizures. Following these episodes, he started avoiding school due of episodic palpitations, 'nervousness' and sweating. However, the episodes of unresponsiveness did not recur. His symptoms were attributed to stress/anxiety by both the examining physicians as well as the parents because repeated clinical evaluation including 12-lead ECG done three times and echocardiography were normal. Fortunately the sixth time, the diagnosis was clinched on an ECG when he presented to the paediatrician with tachycardia and hypotension. PMID- 22674954 TI - Effusive-constrictive pericarditis in the absence of overt pericardial disease on multiple imaging modalities. AB - Effusive-constrictive pericarditis (ECP) is a rare condition that may prove fatal without appropriate treatment. In ECP, there is concomitant existence of a pericardial effusion and CP, that together lead to impaired cardiac filling. Therapeutic pericardiocentesis only addresses part of the problem; surgical pericardiectomy may be required to relieve the constrictive element. Imaging in ECP characteristically demonstrates calcification or thickening of the pericardium. The authors describe a case of ECP were a number of imaging modalities (including echocardiography, cardiac magnetic resonance and CT) did not identify overt pericardial disease. The patient underwent surgical pericardiectomy that led to a rapid resolution of symptoms and full recovery. Histopathological analysis of the pericardial biopsy indicated a non-specific pericardial fibrosis, in keeping with the final diagnosis of ECP. PMID- 22674955 TI - Superficial siderosis associated with abundant tau and alpha-synuclein accumulation. AB - A Japanese male developed deafness, pyramidal signs and ataxia at age 50. A cerebrospinal fluid examination showed elevated levels of iron, transferrin and ferritin. Brain MRI showed atrophy of the cerebellum and pons as well as potential iron deposits on the surface of the brain. At autopsy, the brain weighed 1090 g and showed severe atrophy and necrosis of the cerebellum. No vascular malformation was observed. Extensive deposits of hemosiderin that were well stained with Berlin blue and ferritin immunohistochemistry were present at the surface and in the superficial layers of the cerebrum, brainstem, cerebellum and spinal cord. In these regions, numerous AT8 (p-tau)-immunopositive deposits were present in neurons and glia. In addition, phosphorylated alpha-synuclein immunopositive Lewy bodies and neurites were observed in the brainstem nuclei. In the present report, the authors derive the novel insight that superficial siderosis is a distinctive entity associated with tauopathy and synucleinopathy. PMID- 22674956 TI - Undue delay in the diagnosis of lung cancer due to the clinician's preoccupation with pre-existing tuberculosis. AB - The authors report the case of a seminomadic older patient who had already received a course of antitubercular treatment and within a few weeks of completion suffered resurgence of symptoms. His treating physician assumed it to be relapse of tuberculosis and hence re-started the patient on antitubercular treatment. Though the mass lesion on CT scan procured by the primary care physician suggested the possibility of a neoplasm, areas of necrosis within the mass led to a 'cavitary appearance', which unfortunately happens to be a feature of tuberculosis. Once the patient presented to the authors, they performed cytological investigations which established that the patient had lung cancer co existing with tuberculosis, which indeed was the reason for his progressive symptoms in spite of antitubercular treatment. PMID- 22674958 TI - A toddler with a yellow nose and excessive intake of sweet potato. PMID- 22674957 TI - Kikuchi-Fujimoto's disease involving mesenteric nodes: a report and review of literature. AB - An adolescent boy underwent laparoscopic evaluation with persisting fever associated with colicky abdominal pain of about 3 weeks duration after a CT study of his abdomen revealed mesenteric adenopathy. Histopathological evaluation of the excised mesenteric nodes showed features of histiocytic necrotising lymphadenopathy suggestive of Kikuchi-Fujimoto lymphadenopathy which was confirmed on immunehistochemistry staining. Kikuchi-Fujimoto's disease involving the mesenteric nodes is extremely unusual and can be confounding with a mistaken diagnosis of and prolonged treatment for tuberculosis. The authors present a case of Kikuchi-Fujimoto's disease involving the mesenteric lymph nodes and discuss the various aspects of diagnosis and management of the case along with a review of published literature. PMID- 22674959 TI - An incidental finding of a gastric foreign body 25 years after ingestion. PMID- 22674960 TI - Sciatica as a presenting feature of thyroid follicular adenocarcinoma in a 79 year-old woman. AB - The authors describe an unusual case of metastatic thyroid follicular adenocarcinoma presenting with sciatica in a 79-year-old woman. The primary thyroid tumour was undiagnosed until this clinical presentation. The patient gave a short history of back pain and right-sided sciatica, which was progressive and nocturnal in nature. Neuroimaging revealed an enhancing intradural mass lesion, which was completely excised through a right L1-L3 hemilaminectomy. Histopathological examination of the excised tissue revealed a follicular thyroid carcinoma. Subsequent metastatic investigation revealed a heterogeneously attenuating mixed solid cystic mass in a retrosternal thyroid gland, with multiple solid pulmonary nodules suggestive of metastatic disease. She opted for palliative radiotherapy for the primary thyroid cancer and made remarkable postoperative improvement. The authors conclude that surgical treatment of solitary metastatic lesion may produce good symptomatic relief irrespective of patient's age and primary pathology, while emphasising the need for detailed clinical evaluation of patients with 'red flag' symptoms. PMID- 22674961 TI - Complete AV-block secondary to lithium-clozapine therapy and relapsing multiple sclerosis in a bipolar patient. AB - A complete atrioventricular block (CAVB) can be a lethal complication when it is not treated directly with isoprenaline and pacemaker therapy. The overall incidence of CAVB varies between 4 to 8 per cent with a mortality OR of 3.2 within 30 days if untreated. Main causes of CAVB are inferior myocardial infarction, congenital AV node malformation, mitral valve insufficiency and valve surgery, metabolic disorders and intoxications. The authors describe a case with a CAVB due to lithium-clozapine therapy and relapsing multiple sclerosis. PMID- 22674962 TI - Hospital practices and breastfeeding rates before and after the UNICEF/WHO 20 hour course for maternity staff. AB - BACKGROUND: The Baby-Friendly Hospital Initiative (BFHI) is the most widely promoted program for increasing breastfeeding rates. OBJECTIVE: To evaluate the impact of BFHI training on hospital practices and breastfeeding rates during the first 12 months of life. METHODS: Eighty percent of maternity medical and nursing staff at the University Hospital in Split, Croatia, completed the updated and expanded United Nations Children's Fund/World Health Organization 20-hour course. Seven hundred seventy-three mothers (388 in the pre- and 385 in the post-training group) were included in a birth cohort and interviewed at discharge and at 3, 6, and 12 months postpartum to evaluate hospital practices and infant feeding. Six out of 10 Baby-Friendly practices were assessed using standard BFHI forms. RESULTS: Three months after training was completed, 3 of the Baby-Friendly practices assessed (Step 4, "Initiate breastfeeding within a half-hour of birth"; Step 7, "Rooming-in"; and Step 8, "Feeding on demand") had significantly improved. The proportion of newborns exclusively breastfed during the first 48 hours increased from 6.0% to 11.7% (P < .005). There was no difference in breastfeeding rates at discharge or at 3, 6, or 12 months between the pre- and post-training groups. CONCLUSION: Training of health professionals, based on the BFHI, was associated with significant improvement in some Baby-Friendly hospital practices and initial exclusive breastfeeding rates. A high rate of in-hospital supplementation may partly explain the lack of improvement in breastfeeding exclusivity and duration after discharge. Strong institutional support and commitment is needed to enable full implementation of recommended Baby-Friendly practices. PMID- 22674963 TI - Milk and social media: online communities and the International Code of Marketing of Breast-milk Substitutes. AB - BACKGROUND: The advent of social networking sites and other online communities presents new opportunities and challenges for the promotion, protection, and support of breastfeeding. This study examines the presence of infant formula marketing on popular US social media sites, using the World Health Organization International Code of Marketing of Breast-milk Substitutes (the Code) as a framework. METHODS: We examined to what extent each of 11 infant formula brands that are widely available in the US had established a social media presence in popular social media venues likely to be visited by expectant parents and families with young children. We then examined current marketing practices, using the Code as a basis for ethical marketing. RESULTS: Infant formula manufacturers have established a social media presence primarily through Facebook pages, interactive features on their own Web sites, mobile apps for new and expecting parents, YouTube videos, sponsored reviews on parenting blogs, and other financial relationships with parenting blogs. Violations of the Code as well as promotional practices unforeseen by the Code were identified. These practices included enabling user-generated content that promotes the use of infant formula, financial relationships between manufacturers and bloggers, and creation of mobile apps for use by parents. An additional concern identified for Code enforcement is lack of transparency in social media-based marketing. CONCLUSION: The use of social media for formula marketing may demand new strategies for monitoring and enforcing the Code in light of emerging challenges, including suggested content for upcoming consideration for World Health Assembly resolutions. PMID- 22674964 TI - Establishing the Baby-Friendly Community Initiative in Italy: development, strategy, and implementation. AB - BACKGROUND: The Baby-Friendly Hospital Initiative (BFHI), developed by the World Health Organization and the United Nations Children's Fund (UNICEF) to promote breastfeeding in maternity facilities worldwide, has had a global impact on breastfeeding outcomes, but other interventions are needed both before and after hospital discharge to meet the recommended targets at 6 months. The Baby-Friendly Community Initiative (BFCI), a multifaceted program for community-based breastfeeding promotion that is complementary to the BFHI, addresses this challenge. OBJECTIVE: To describe the development, strategy, and implementation of the BFCI in Italy. METHODS: In 2006, UNICEF Italy created a working group to develop the BFCI for the Italian health system. A review of the different BFCI models worldwide was conducted. A preliminary adaptation of tools to Italian community health care settings was developed in 2007, when the Italian BFCI Seven Steps were published. Two years later, UNICEF Italy launched the Standards for Best Practice for both hospitals and communities, based on 2009 BFHI and UNICEF UK BFCI materials. OUTCOMES: The main outcome was to promote this process in Italian regional health systems and develop tools to assess compliance with the BFCI criteria. There is now one fully accredited Baby-Friendly Community in Italy, and 17 other communities are working on the various stages. CONCLUSIONS: The BFCI, a complex program that involves participation, training, audits, a continuous flow of feedback, and provision of resources for health workers and families, is now a reality in Italy. PMID- 22674965 TI - Breastfeeding support in neonatal intensive care: a national survey. AB - BACKGROUND: The incidence of breastfeeding of preterm infants is affected by the support provided at the hospital and in the neonatal intensive care unit (NICU). However, policies and guidelines promoting breastfeeding vary both nationally and internationally. OBJECTIVES: The aim of this survey was to describe breastfeeding support in Danish NICUs, where approximately 98% of mothers initiate lactation. METHODS: A national survey of all 19 Danish NICUs was conducted in 2009. Four NICUs were at designated Baby-Friendly hospitals, and 5 had a lactation consultant. In all NICUs, it was possible for some parents to stay overnight; 2 units had short restrictions on parents' presence. Five NICUs had integrated postpartum care for mothers. Breastfeeding policies, written guidelines, and systematic breastfeeding training for the staff were common in most NICUs. Seventeen NICUs recommended starting breast milk expression within 6 hours after birth, and mothers were encouraged to double pump. Most NICUs aimed to initiate skin-to-skin contact the first time the parents were in the NICU, and daily skin to-skin contact was estimated to last for 2-4 hours in 63% and 4-8 hours in 37% of the units. The use of bottle-feeding was restricted. CONCLUSIONS: The Danish NICUs described the support of breastfeeding as a high priority, which was reflected in the recommended policies for breast milk pumping, skin-to-skin contact, and the parents' presence in the NICU, as well as in the restricted use of bottle-feeding. However, support varied between units, and not all units supported optimal breastfeeding. PMID- 22674966 TI - Breastfeeding knowledge, attitudes, prior exposure, and intent among undergraduate students. AB - BACKGROUND: Understanding breastfeeding knowledge, attitudes, and exposures among nonpregnant youth who are likely to be future parents may provide significant pathways to successfully increasing breastfeeding as the normal, accepted way of feeding infants. However, based on a recent review of the literature, only 3 studies have assessed these factors in nonpregnant, young adults in the United States in the past 10 years. OBJECTIVE: The objective of this study was to gather more recent data regarding breastfeeding knowledge, attitudes, and prior exposure among undergraduate university students. METHODS: This was a cross-sectional survey, conducted in November 2010. A convenience sample, consisting of undergraduates in attendance in 2 sections of an introductory nutrition class at a large research university, was used for this project (N = 248). RESULTS: Breastfeeding knowledge was relatively good. However, overall breastfeeding attitudes were more neutral, which appeared to be explained by the belief that breastfeeding is painful, restrictive, and inconvenient, both in general and specifically for the working mother. Though support for breastfeeding in public was low, men were significantly less likely than women to believe it to be embarrassing or unacceptable. In addition, breastfeeding attitudes were more positive among older students and those who were breastfed as infants. Those who were breastfed as infants were also significantly more likely to intend to breastfeed future children. CONCLUSIONS: Though this sample indicates good breastfeeding knowledge, attitudes were more neutral, and support for breastfeeding in public appears low. This finding is contradictory and warrants further exploration. PMID- 22674967 TI - Expansion of the ten steps to successful breastfeeding into neonatal intensive care: expert group recommendations for three guiding principles. AB - The World Health Organization/United Nations Children's Fund Baby-Friendly Hospital Initiative: Revised, Updated, and Expanded for Integrated Care (2009) identifies the need for expanding the guidelines originally developed for maternity units to include neonatal intensive care. For this purpose, an expert group from the Nordic countries and Quebec, Canada, prepared a draft proposal, which was discussed at an international workshop in Uppsala, Sweden, in September 2011. The expert group suggests the addition of 3 "Guiding Principles" to the Ten Steps to support this vulnerable population of mothers and infants: 1. The staff attitude to the mother must focus on the individual mother and her situation. 2. The facility must provide family-centered care, supported by the environment. 3. The health care system must ensure continuity of care, that is, continuity of pre , peri-, and postnatal care and post-discharge care. The goal of the expert group is to create a final document, the Baby Friendly Hospital Initiative for Neonatal Units, including standards and criteria for each of the 3 Guiding Principles, Ten Steps, and the Code; to develop tools for self-appraisal and monitoring compliance with the guidelines; and for external assessment to decide whether neonatal intensive/intermediate care units meet the conditions required to be designated as Baby-Friendly. The documents will be finalized after consultation with the World Health Organization/United Nations Children's Fund, and the goal is to offer these documents to international health care, professional, and other nongovernmental organizations involved in lactation and breastfeeding support for mothers of infants who require special neonatal care. PMID- 22674968 TI - Antidepressant-like effect of creatine in mice involves dopaminergic activation. AB - Creatine has been shown to play a significant role in health and disease. However, studies concerning its effect on mood are scarce. This study investigated the effect of creatine (p.o.) in the tail suspension test, a predictive test of antidepressant activity. Creatine reduced the immobility time in the tail suspension test (0.1-1000 mg/kg, male and female mice), without affecting locomotor activity. Furthermore, the involvement of the dopaminergic system in creatine-induced antidepressant-like effect in male mice in the tail suspension test was investigated. The anti-immobility effect of creatine (1 mg/kg) was prevented by the pre-treatment of mice with haloperidol (0.2 mg/kg, intraperitoneal (i.p.) route, non-selective dopamine receptor antagonist), (R) (+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH23390; 0.05 mg/kg, subcutaneous (s.c.) route, dopamine D1 receptor antagonist) and sulpiride (50 mg/kg, i.p., dopamine D2 receptor antagonist). Creatine (0.01 mg/kg, sub-effective dose) in combination with sub effective doses of (1-phenyl-7,8-dihydroxy-2,3,4,5-tetrahydro-1H-3-benzazepine) hydrochloride (SKF38393; 0.1 mg/kg, s.c., dopamine D1 receptor agonist), apomorphine (0.5 ug/kg, i.p., preferential dopamine D2 receptor agonist) or bupropion (1 mg/kg, p.o., dopamine reuptake inhibitor with subtle activity on noradrenergic reuptake) reduced the immobility time in the tail suspension test as compared with either drug alone. These results indicate that the antidepressant-like effect of creatine is likely mediated by an activation of dopamine D1 and D2 receptors. PMID- 22674969 TI - Gemcitabine-induced severe peripheral edema in a patient with lung cancer. AB - Gemcitabine, alone or in combination with a platinum-based agent, is indicated for the first-line treatment of patients with locally advanced or metastatic non small-cell lung cancer. It is generally a well-tolerated drug. Despite its lack of significant toxicity, the most commonly reported side effects include myelosuppression, gastrointestinal disturbances (eg, nausea and vomiting), influenza-like symptoms, skin rash with pruritus, and elevation of liver transaminase enzymes. Peripheral edema has rarely been described as an adverse effect. Herein, we report a patient with advanced non-small-cell lung cancer who experienced severe peripheral edema after gemcitabine administration. Immediate gemcitabine discontinuation and the administration of diuretics resulted in definite regression of peripheral edema. PMID- 22674970 TI - Clinical pharmacogenomics of warfarin and clopidogrel. AB - Genetic polymorphisms significantly influence responses to warfarin and clopidogrel. Polymorphisms in the cytochrome P450 (CYP) 2C9 and vitamin K epoxide reductase genes change warfarin pharmacokinetics and pharmacodynamics, respectively. Because these polymorphisms influence warfarin dose requirements, they may primarily help determine therapeutic warfarin doses in patients who newly start on the drug. To assist in estimating therapeutic warfarin doses, the warfarin label provides a pharmacogenomic dosing table and various warfarin pharmacogenomic dosing algorithms are available. On the other hand, polymorphisms in the CYP2C19 gene affect clopidogrel pharmacokinetics. These polymorphisms may be useful to identify clopidogrel nonresponders who may benefit from taking an alternative antiplatelet agent such as prasugrel and ticagrelor. Although both drugs have pharmacogenomic tests available for clinical use, their clinical utilities have not been established and are currently being actively studied. In this review, clinical application of warfarin and clopidogrel pharmacogenomics will be focused. With the current level of evidence, potential patients who may get benefit from warfarin and clopidogrel pharmacogenomic testing will be discussed. In addition, the interpretation of the warfarin and clopidogrel test results and the current barriers to widespread use of warfarin and clopidogrel pharmacogenomic testing will be discussed. PMID- 22674971 TI - An insertion/deletion ACE polymorphism and kidney size in Polish full-term newborns. AB - The number of nephrons is a multifactorial trait controlled by the interaction of environmental factors and genetic variants that influence the extent of branching nephrogenesis during foetal life. A correlation between renal mass and nephron number in newborns allows the use of the total kidney volume at birth as a surrogate for congenital nephron number. Since the renin-angiotensin system plays an important role in renal development we hypothesized that the common, functional insertion/deletion (I/D) polymorphism in the ACE gene might be responsible for the variation in kidney size amongst healthy individuals. We recruited 210 healthy Polish full-term newborns born to healthy women with uncomplicated pregnancies. The kidney volume was measured sonographically. Total kidney volume (TKV) was calculated as the sum of left kidney volume and right kidney volume. TKV was normalized to body surface area (TKV/BSA). The I and D alleles were identified using polymerase chain reaction. TKV/BSA in newborns carrying at least one insertion ACE allele was significantly reduced by approximately 8% as compared with homozygous newborns for the D allele (DD genotype) (105.1+/-23.6 vs. 114.2+/-28.2 cm(3)/m(2), p<0.05). The results of this study suggest that I/D ACE polymorphism may account for subtle variation in kidney size at birth, which reflects congenital nephron endowment. PMID- 22674972 TI - Balance exercise for persons with multiple sclerosis using Wii games: a randomised, controlled multi-centre study. AB - BACKGROUND: The use of interactive video games is expanding within rehabilitation. The evidence base is, however, limited. OBJECTIVE: Our aim was to evaluate the effects of a Nintendo Wii Fit(r) balance exercise programme on balance function and walking ability in people with multiple sclerosis (MS). METHODS: A multi-centre, randomised, controlled single-blinded trial with random allocation to exercise or no exercise. The exercise group participated in a programme of 12 supervised 30-min sessions of balance exercises using Wii games, twice a week for 6-7 weeks. Primary outcome was the Timed Up and Go test (TUG). In total, 84 participants were enrolled; four were lost to follow-up. RESULTS: After the intervention, there were no statistically significant differences between groups but effect sizes for the TUG, TUGcognitive and, the Dynamic Gait Index (DGI) were moderate and small for all other measures. Statistically significant improvements within the exercise group were present for all measures (large to moderate effect sizes) except in walking speed and balance confidence. The non-exercise group showed statistically significant improvements for the Four Square Step Test and the DGI. CONCLUSION: In comparison with no intervention, a programme of supervised balance exercise using Nintendo Wii Fit(r) did not render statistically significant differences, but presented moderate effect sizes for several measures of balance performance. PMID- 22674973 TI - Selection of classical swine fever virus with enhanced pathogenicity reveals synergistic virulence determinants in E2 and NS4B. AB - Classical swine fever virus (CSFV) is the causative agent of classical swine fever (CSF), a highly contagious disease of pigs. There are numerous CSFV strains that differ in virulence, resulting in clinical disease with different degrees of severity. Low-virulent and moderately virulent isolates cause a mild and often chronic disease, while highly virulent isolates cause an acute and mostly lethal hemorrhagic fever. The live attenuated vaccine strain GPE(-) was produced by multiple passages of the virulent ALD strain in cells of swine, bovine, and guinea pig origin. With the aim of identifying the determinants responsible for the attenuation, the GPE(-) vaccine virus was readapted to pigs by serial passages of infected tonsil homogenates until prolonged viremia and typical signs of CSF were observed. The GPE(-)/P-11 virus isolated from the tonsils after the 11th passage in vivo had acquired 3 amino acid substitutions in E2 (T830A) and NS4B (V2475A and A2563V) compared with the virus before passages. Experimental infection of pigs with the mutants reconstructed by reverse genetics confirmed that these amino acid substitutions were responsible for the acquisition of pathogenicity. Studies in vitro indicated that the substitution in E2 influenced virus spreading and that the changes in NS4B enhanced the viral RNA replication. In conclusion, the present study identified residues in E2 and NS4B of CSFV that can act synergistically to influence virus replication efficiency in vitro and pathogenicity in pigs. PMID- 22674975 TI - Transport to late endosomes is required for efficient reovirus infection. AB - Rab GTPases play an essential role in vesicular transport by coordinating the movement of various types of cargo from one cellular compartment to another. Individual Rab GTPases are distributed to specific organelles and thus serve as markers for discrete types of endocytic vesicles. Mammalian reovirus binds to cell surface glycans and junctional adhesion molecule-A (JAM-A) and enters cells by receptor-mediated endocytosis in a process dependent on beta1 integrin. Within organelles of the endocytic compartment, reovirus undergoes stepwise disassembly catalyzed by cathepsin proteases, which allows the disassembly intermediate to penetrate endosomal membranes and release the transcriptionally active viral core into the cytoplasm. The pathway used by reovirus to traverse the endocytic compartment is largely unknown. In this study, we found that reovirus particles traffic through early, late, and recycling endosomes during cell entry. After attachment to the cell surface, reovirus particles and JAM-A codistribute into each of these compartments. Transfection of cells with constitutively active and dominant-negative Rab GTPases that affect early and late endosome biogenesis and maturation influenced reovirus infectivity. In contrast, reovirus infectivity was not altered in cells expressing mutant Rab GTPases that affect recycling endosomes. Thus, reovirus virions localize to early, late, and recycling endosomes during entry into host cells, but only those that traverse early and late endosomes yield a productive infection. PMID- 22674974 TI - Hepatitis C virus NS5A disrupts STAT1 phosphorylation and suppresses type I interferon signaling. AB - Responses to alpha interferon (IFN-alpha)-based treatment are dependent on both host and viral factors and vary markedly among patients infected with different hepatitis C virus (HCV) genotypes (GTs). Patients infected with GT3 viruses consistently respond better to IFN treatment than do patients infected with GT1 viruses. The mechanisms underlying this difference are not well understood. In this study, we sought to determine the effects of HCV NS5A proteins from different genotypes on IFN signaling. We found that the overexpression of either GT1 or GT3 NS5A proteins significantly inhibited IFN-induced IFN-stimulated response element (ISRE) signaling, phosphorylated STAT1 (P-STAT1) levels, and IFN stimulated gene (ISG) expression compared to controls. GT1 NS5A protein expression exhibited stronger inhibitory effects on IFN signaling than did GT3 NS5A protein expression. Furthermore, GT1 NS5A bound to STAT1 with a higher affinity than did GT3 NS5A. Domain mapping revealed that the C-terminal region of NS5A conferred these inhibitory effects on IFN signaling. The overexpression of HCV NS5A increased HCV replication levels in JFH1-infected cells through the further reduction of levels of P-STAT1, ISRE signaling, and downstream ISG responses. We demonstrated that the overexpression of GT1 NS5A proteins resulted in less IFN responsiveness than did the expression of GT3 NS5A proteins through stronger binding to STAT1. We confirmed that GT1 NS5A proteins exerted stronger IFN signaling inhibition than did GT3 NS5A proteins in an infectious recombinant JFH1 virus. The potent antiviral NS5A inhibitor BMS-790052 did not block NS5A mediated IFN signaling suppression in an overexpression model, suggesting that NS5A's contributions to replication are independent of its subversive action on IFN. We propose a model in which the binding of the C-terminal region of NS5A to STAT1 leads to decreased levels of P-STAT1, ISRE signaling, and ISG transcription and, ultimately, to preferential GT1 resistance to IFN treatment. PMID- 22674976 TI - Effect of priming with H1N1 influenza viruses of variable antigenic distances on challenge with 2009 pandemic H1N1 virus. AB - Compared to seasonal influenza viruses, the 2009 pandemic H1N1 (pH1N1) virus caused greater morbidity and mortality in children and young adults. People over 60 years of age showed a higher prevalence of cross-reactive pH1N1 antibodies, suggesting that they were previously exposed to an influenza virus or vaccine that was antigenically related to the pH1N1 virus. To define the basis for this cross-reactivity, ferrets were infected with H1N1 viruses of variable antigenic distance that circulated during different decades from the 1930s (Alaska/35), 1940s (Fort Monmouth/47), 1950s (Fort Warren/50), and 1990s (New Caledonia/99) and challenged with 2009 pH1N1 virus 6 weeks later. Ferrets primed with the homologous CA/09 or New Jersey/76 (NJ/76) virus served as a positive control, while the negative control was an influenza B virus that should not cross-protect against influenza A virus infection. Significant protection against challenge virus replication in the respiratory tract was observed in ferrets primed with AK/35, FM/47, and NJ/76; FW/50-primed ferrets showed reduced protection, and NC/99-primed ferrets were not protected. The hemagglutinins (HAs) of AK/35, FM/47, and FW/50 differ in the presence of glycosylation sites. We found that the loss of protective efficacy observed with FW/50 was associated with the presence of a specific glycosylation site. Our results suggest that changes in the HA occurred between 1947 and 1950, such that prior infection could no longer protect against 2009 pH1N1 infection. This provides a mechanistic understanding of the nature of serological cross-protection observed in people over 60 years of age during the 2009 H1N1 pandemic. PMID- 22674977 TI - Structure and receptor complexes of the hemagglutinin from a highly pathogenic H7N7 influenza virus. AB - Recurrence of highly pathogenic avian influenza (HPAI) virus subtype H7 in poultry continues to be a public health concern. In 2003, an HPAI H7N7 outbreak in The Netherlands infected 89 people in close contact with affected poultry and resulted in one fatal case. In previous studies, the virus isolated from this fatal case, A/Netherlands/219/2003 (NL219) caused a lethal infection in mouse models and had increased replication efficiency and a broader tissue distribution than nonlethal isolates from the same outbreak. A mutation which introduces a potential glycosylation site at Asn123 in the NL219 hemagglutinin was postulated to contribute to the pathogenic properties of this virus. To study this further, we have expressed the NL219 hemagglutinin in a baculovirus expression system and performed a structural analysis of the hemagglutinin in complex with avian and human receptor analogs. Glycan microarray and kinetic analysis were performed to compare the receptor binding profile of the wild-type recombinant NL219 HA to a variant with a threonine-to-alanine mutation at position 125, resulting in loss of the glycosylation site at Asn123. The results suggest that the additional glycosylation sequon increases binding affinity to avian-type alpha2-3-linked sialosides rather than switching to a human-like receptor specificity and highlight the mechanistic diversity of these pathogens, which calls attention to the need for further studies to fully understand the unique properties of these viruses. PMID- 22674978 TI - Interactions between proteins encoded within the human cytomegalovirus UL133 UL138 locus. AB - We previously described a novel genetic locus within the ULb' region of the human cytomegalovirus (HCMV) genome that, while dispensable for replication in fibroblasts, suppresses replication in hematopoietic progenitors and augments replication in endothelial cells. This locus, referred to as the UL133-UL138 locus, encodes four proteins, pUL133, pUL135, pUL136, and pUL138. In this work, we have mapped the interactions among these proteins. An analysis of all pairwise interactions during transient expression revealed a robust interaction between pUL133 and pUL138. Potential interactions between pUL136 and both pUL133 and pUL138 were also revealed. In addition, each of the UL133-UL138 locus proteins self-associated, suggesting a potential to form higher-order homomeric complexes. As both pUL133 and pUL138 function in promoting viral latency in CD34(+) hematopoietic progenitor cells (HPCs) infected in vitro, we further focused on this interaction. pUL133 and pUL138 are the predominant complex detected when all proteins are expressed together and require no other proteins in the locus for their association. During infection, the interaction between pUL133 and pUL138 or pUL136 can be detected. A recombinant virus that fails to express both pUL133 and pUL138 exhibited a latency phenotype similar to that of viruses that fail to express either pUL133 or pUL138, indicating that these proteins function cooperatively in latency and do not have independent functions that additively contribute to HCMV latency. These studies identify protein interactions among proteins encoded by the UL133-UL138 locus and demonstrate an important interaction impacting the outcome of HCMV infection. PMID- 22674979 TI - Identification of novel T cell factor 4 (TCF-4) binding sites on the HIV long terminal repeat which associate with TCF-4, beta-catenin, and SMAR1 to repress HIV transcription. AB - Molecular regulation of HIV transcription is a multifaceted process dictated in part by the abundance of cellular transcription factors that induce or repress HIV promoter activity. beta-Catenin partners with members of the T cell factor (TCF)/LEF transcription factors to regulate gene expression. The interaction between beta-catenin and TCF-4 is linked to inhibition of HIV replication in multiple cell types, including lymphocytes and astrocytes. Here, we evaluated the molecular mechanism by which beta-catenin/TCF-4 repress HIV replication. We identified for the first time multiple TCF-4 binding sites at -336, -143, +66, and +186 relative to the transcription initiation site on the HIV long terminal repeat (LTR). Two of the sites (-143 and +66) were present in approximately 1/3 of 500 HIV-1 isolates examined. Although all four sites could bind to TCF-4, the strongest association occurred at -143. Deletion and/or mutation of -143, in conjunction with beta-catenin or TCF-4 knockdown in cells stably expressing an LTR reporter construct, enhanced basal HIV promoter activity by 5-fold but had no effect on Tat-mediated transactivation of the HIV LTR. We also found that TCF-4, beta-catenin, and the nuclear matrix binding protein SMAR1 tether at the -143 nucleotide (nt) site on the HIV LTR to inhibit HIV promoter activity. Collectively, these data indicate that TCF-4 and beta-catenin at -143 associate with SMAR1, which likely pulls the HIV DNA segment into the nuclear matrix and away from transcriptional machinery, leading to repression of basal HIV LTR transcription. These studies point to novel avenues for regulation of HIV replication by manipulation of beta-catenin signaling within cells. PMID- 22674980 TI - ORF7 of varicella-zoster virus is a neurotropic factor. AB - Varicella-zoster virus (VZV) is the causative agent of chickenpox and herpes zoster (shingles). After the primary infection, the virus remains latent in sensory ganglia and reactivates upon weakening of the cellular immune system due to various conditions, erupting from sensory neurons and infecting the corresponding skin tissue. The current varicella vaccine is highly attenuated in the skin and yet retains its neurovirulence and may reactivate and damage sensory neurons. The factors involved in neuronal invasion and establishment of latency are still elusive. Previously, we constructed a library of whole-gene deletion mutants carrying a bacterial artificial chromosome sequence and a luciferase marker in order to perform a comprehensive VZV genome functional analysis. Here, screening of dispensable gene deletion mutants in differentiated neuronal cells led to the identification of ORF7 as the first known, likely a main, VZV neurotropic factor. ORF7 is a virion component localized to the Golgi compartment in infected cells, whose deletion causes loss of polykaryon formation in epithelial cell culture. Interestingly, ORF7 deletion completely abolishes viral spread in human nervous tissue ex vivo and in an in vivo mouse model. This finding adds to our previous report that ORF7 is also a skin-tropic factor. The results of our investigation will not only lead to a better understanding of VZV neurotropism but could also contribute to the development of a neuroattenuated vaccine candidate against shingles or a vector for delivery of other antigens. PMID- 22674981 TI - Structural variability of the herpes simplex virus 1 genome in vitro and in vivo. AB - Herpes simplex virus 1 (HSV-1) is a human pathogen that leads to recurrent facial oral lesions. Its 152-kb genome is organized in two covalently linked segments, each composed of a unique sequence flanked by inverted repeats. Replication of the HSV-1 genome produces concatemeric molecules in which homologous recombination events occur between the inverted repeats. This mechanism leads to four genome isomers (termed P, IS, IL, and ILS) that differ in the relative orientations of their unique fragments. Molecular combing analysis was performed on DNA extracted from viral particles and BSR, Vero, COS-7, and Neuro-2a cells infected with either strain SC16 or KOS of HSV-1, as well as from tissues of experimentally infected mice. Using fluorescence hybridization, isomers were repeatedly detected and distinguished and were accompanied by a large proportion of noncanonical forms (40%). In both cell and viral-particle extracts, the distributions of the four isomers were statistically equivalent, except for strain KOS grown in Vero and Neuro-2a cells, in which P and IS isomers were significantly overrepresented. In infected cell extracts, concatemeric molecules as long as 10 genome equivalents were detected, among which, strikingly, the isomer distributions were equivalent, suggesting that any such imbalance may occur during encapsidation. In vivo, for strain KOS-infected trigeminal ganglia, an unbalanced distribution distinct from the one in vitro was observed, along with a considerable proportion of noncanonical assortment. PMID- 22674982 TI - Hepatitis C virus upregulates Beclin1 for induction of autophagy and activates mTOR signaling. AB - Hepatitis C virus (HCV) induces autophagosome formation in infected human hepatocytes. We have previously reported that HCV exploits autophagic machinery in favor of virus growth and survival in host cells (S. Shrivastava et al., Hepatology 53:406-414, 2011); however, the mechanisms for autophagy induction is poorly understood. In the present study, we observed that HCV infection transcriptionally upregulates Beclin1, which forms complex with Vps34, the class III phosphatidylinositol 3-kinase, as a first step for autophagy initiation. Although Bcl-2 has an anti-autophagy effect by its association with Beclin1 in nutrient-deprived cells, our studies revealed that HCV-mediated autophagy occurs independent of Beclin1-Bcl-2 dissociation. Mammalian target of rapamycin (mTOR) is a positive regulator of cell growth and is recognized as an inhibitor of autophagy induction. Our results demonstrated that HCV infection enhances phospho mTOR expression and its downstream target 4EBP1 activation, suggesting that mTOR is not a negative regulator of HCV-induced autophagy. On the other hand, HCV infection in autophagy-impaired cells reduced phospho-mTOR, mTOR, and phospho 4EBP1 expression. Together, these results suggested that HCV induces autophagy by upregulating Beclin1 and activates mTOR signaling pathway, which in turn may promote hepatocyte growth. PMID- 22674983 TI - Infectious endogenous retroviruses in cats and emergence of recombinant viruses. AB - Endogenous retroviruses (ERVs) comprise a significant percentage of the mammalian genome, and it is poorly understood whether they will remain as inactive genomes or emerge as infectious retroviruses. Although several types of ERVs are present in domestic cats, infectious ERVs have not been demonstrated. Here, we report a previously uncharacterized class of endogenous gammaretroviruses, termed ERV-DCs, that is present and hereditary in the domestic cat genome. We have characterized a subset of ERV-DC proviral clones, which are numbered according to their genomic insertions. One of these, ERV-DC10, located in the q12-q21 region on chromosome C1, is an infectious gammaretrovirus capable of infecting a broad range of cells, including human. Our studies indicate that ERV-DC10 entered the genome of domestic cats in the recent past and appeared to translocate to or reintegrate at a distinct locus as infectious ERV-DC18. Insertional polymorphism analysis revealed that 92 of 244 domestic cats had ERV-DC10 on a homozygous or heterozygous locus. ERV-DC-like sequences were found in primate and rodent genomes, suggesting that these ERVs, and recombinant viruses such as RD-114 and BaEV, originated from an ancestor of ERV-DC. We also found that a novel recombinant virus, feline leukemia virus subgroup D (FeLV-D), was generated by ERV-DC env transduction into feline leukemia virus in domestic cats. Our results indicate that ERV-DCs behave as donors and/or acceptors in the generation of infectious, recombinant viruses. The presence of such infectious endogenous retroviruses, which could be harmful or beneficial to the host, may affect veterinary medicine and public health. PMID- 22674984 TI - Interleukin-1R signaling is essential for induction of proapoptotic CD8 T cells, viral clearance, and pathology during lymphocytic choriomeningitis virus infection in mice. AB - The T cell granule exocytosis pathway is essential to control hepatotropic lymphocytic choriomeningitis virus strain WE (LCMV-WE) but also contributes to the observed pathology in mice. Although effective antiviral T cell immunity and development of viral hepatitis are strictly dependent on perforin and granzymes, the molecular basis underlying induction of functionally competent virus-immune T cells, including participation of the innate immune system, is far from being resolved. We demonstrate here that LCMV-immune T cells of interleukin-1 receptor (IL-1R)-deficient mice readily express transcripts for perforin and granzymes but only translate perforin, resulting in the lack of proapoptotic potential in vitro. LCMV is not cleared in IL-1R-deficient mice, and yet the infected mice develop neither splenomegaly nor hepatitis. These results demonstrate that IL-1R signaling is central to the induction of proapoptotic CD8 T cell immunity, including viral clearance and associated tissue injuries in LCMV infection. PMID- 22674985 TI - Antibody-dependent cellular cytotoxicity against primary HIV-infected CD4+ T cells is directly associated with the magnitude of surface IgG binding. AB - Antibody (Ab)-dependent cellular cytotoxicity (ADCC) is thought to potentially play a role in vaccine-induced protection from HIV-1. The characteristics of such antibodies remain incompletely understood. Furthermore, correlates between ADCC and HIV-1 immune status are not clearly defined. We screened the sera of 20 HIV-1 positive (HIV-1(+)) patients for ADCC. Normal human peripheral blood mononuclear cells were used to derive HIV-infected CD4(+) T cell targets and autologous, freshly isolated, natural killer (NK) cells in a novel assay that measures granzyme B (GrB) and HIV-1-infected CD4(+) T cell elimination (ICE) by flow cytometry. We observed that complex sera mediated greater levels of ADCC than anti-HIV-1 envelope glycoprotein (Env)-specific monoclonal antibodies and serum mediated ADCC correlated with the amount of IgG and IgG1 bound to HIV-1-infected CD4(+) T cells. No correlation between ADCC and viral load, CD4(+) T cell count, or neutralization of HIV-1(SF162) or other primary viral isolates was detected. Sera pooled from clade B HIV-1(+) individuals exhibited breadth in killing targets infected with HIV-1 from clades A/E, B, and C. Taken together, these data suggest that the total amount of IgG bound to an HIV-1-infected cell is an important determinant of ADCC and that polyvalent antigen-specific Abs are required for a robust ADCC response. In addition, Abs elicited by a vaccine formulated with immunogens from a single clade may generate a protective ADCC response in vivo against a variety of HIV-1 species. Increased understanding of the parameters that dictate ADCC against HIV-1-infected cells will inform efforts to stimulate ADCC activity and improve its potency in vaccinees. PMID- 22674986 TI - Revisiting the clinal concept of evolution and dispersal for the tick-borne flaviviruses by using phylogenetic and biogeographic analyses. AB - Tick-borne flaviviruses (TBF) are widely dispersed across Africa, Europe, Asia, Oceania, and North America, and some present a significant threat to human health. Seminal studies on tick-borne encephalitis viruses (TBEV), based on partial envelope gene sequences, predicted a westward clinal pattern of evolution and dispersal across northern Eurasia, terminating in the British Isles. We tested this hypothesis using all available full-length open reading frame (ORF) TBF sequences. Phylogenetic analysis was consistent with current reports. However, linear and nonlinear regression analysis of genetic versus geographic distance combined with BEAST analysis identified two separate clines, suggesting that TBEV spread both east and west from a central point. In addition, BEAST analysis suggested that TBF emerged and dispersed more than 16,000 years ago, significantly earlier than previously predicted. Thus, climatic and ecological changes may have played a greater role in TBF dispersal than humans. PMID- 22674987 TI - Cell culture-adaptive mutations promote viral protein-protein interactions and morphogenesis of infectious hepatitis C virus. AB - Recent genetic studies suggested that viral nonstructural (NS) proteins play important roles in morphogenesis of flaviviruses, particularly hepatitis C virus (HCV). Adaptive and compensatory mutations occurring in different NS proteins were demonstrated to promote HCV production in cell culture. However, the underlying molecular mechanism of NS proteins in HCV morphogenesis is poorly understood. We have isolated a cell culture-adapted HCV of genotype 2a (JFH1) which grew to an infectious titer 3 orders of magnitude higher than that of wild type virus. Sequence analysis identified a total of 16 amino acid mutations in core (C), E1, NS2, NS3, NS5A, and NS5B, with the majority of mutations clustered in NS5A. Reverse genetic analysis of these mutations individually or in different combinations demonstrated that amino acid mutations in NS2 and NS5A markedly enhanced HCV production. Additionally, mutations in C, E1, NS3, and NS5B synergistically promoted HCV production in the background of NS2 and NS5A mutations. Adaptive mutations in NS5A domains I, II, and III independently enhanced HCV production, suggesting that all three domains of NS5A are important for HCV morphogenesis. More importantly, adaptive mutations greatly enhanced physical interactions among HCV structural and NS proteins, as determined by studies with coimmunoprecipitation and mammalian two-hybrid assays. Collectively, these findings demonstrate that adaptive mutations can enhance specific protein protein interactions among viral structural and NS proteins and therefore promote the assembly of infectious HCV particles. PMID- 22674988 TI - Identification of a novel antiviral inhibitor of the flavivirus guanylyltransferase enzyme. AB - Arthropod-borne flavivirus infection causes serious morbidity and mortality worldwide, but there are currently no effective antiflaviviral chemotherapeutics available for human use. Therefore, it is critical that new therapeutics against virus-specific targets be developed. To identify new compounds that may be used as broadly active flavivirus therapeutics, we have performed a high-throughput screening of 235,456 commercially available compounds for small-molecule inhibitors of the dengue virus NS5 RNA capping enzyme. We identified a family of compounds, the 2-thioxothiazolidin-4-ones, that show potent biochemical inhibition of capping enzyme GTP binding and guanylyltransferase function. During the course of structure-activity relationship analysis, a molecule within this family, (E)-{3-[5-(4-tert-butylbenzylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3 yl]propanoic acid} (BG-323), was found to possess significant antiviral activity in a dengue virus subgenomic replicon assay. Further testing of BG-323 demonstrated that this molecule is able to reduce the replication of infectious West Nile virus and yellow fever virus in cell culture with low toxicity. The results of this study describe the first inhibitor that targets the GTP binding/guanylyltransferase activity of the flavivirus RNA capping enzyme. PMID- 22674989 TI - Kaposi's sarcoma-associated herpesvirus ORF54/dUTPase downregulates a ligand for the NK activating receptor NKp44. AB - Kaposi's sarcoma-associated herpesvirus (KSHV) establishes long-term latent infection in humans and can cause cancers in endothelial and B cells. A functioning immune system is vital for restricting viral proliferation and preventing KSHV-dependent neoplasms. While natural killer (NK) lymphocytes are known to target virus-infected cells for destruction, their importance in the anti-KSHV immune response is not currently understood. Activating receptors on NK cells recognize ligands on target cells, including the uncharacterized ligand(s) for NKp44, termed NKp44L. Here we demonstrate that several NK ligands are affected when KSHV-infected cells are induced to enter the lytic program. We performed a screen of most of the known KSHV genes and found that the product of the ORF54 gene could downregulate NKp44L. The ORF54-encoded protein is a dUTPase; however, dUTPase activity is neither necessary nor sufficient for the downregulation of NKp44L. In addition, we find that ORF54 can also target proteins of the cytokine receptor family and the mechanism of downregulation involves perturbation of membrane protein trafficking. The ORF54-related proteins of other human herpesviruses do not possess this activity, suggesting that the KSHV homolog has evolved a novel immunoregulatory function and that the NKp44 NKp44L signaling pathway contributes to antiviral immunity. PMID- 22674990 TI - A vesiculovirus showing a steepened transcription gradient and dominant trans repression of virus transcription. AB - Vesicular stomatitis virus (VSV) is a prototype nonsegmented, negative-sense virus used to examine viral functions of a broad family of viruses, including human pathogens. Here we demonstrate that S(2) VSV, an isolate with a small plaque phenotype compared to other Indiana strain viruses, has a transcription defect resulting in an altered pattern and rapid decline of transcription. The S(2) VSV transcription gradient is dominant over the wild-type transcription in a coinfection. This is the first characterization of an altered gradient of transcription not dependent on RNA template sequence or host response and may provide insight into new approaches to viral attenuation. PMID- 22674991 TI - Drosophila melanogaster as a model organism for bluetongue virus replication and tropism. AB - Bluetongue virus (BTV) is the etiological agent of bluetongue (BT), a hemorrhagic disease of ruminants that can cause high levels of morbidity and mortality. BTV is an arbovirus transmitted between its ruminant hosts by Culicoides biting midges (Diptera: Ceratopogonidae). Recently, Europe has experienced some of the largest BT outbreaks ever recorded, including areas with no known history of the disease, leading to unprecedented economic and animal welfare issues. The current lack of genomic resources and genetic tools for Culicoides restricts any detailed study of the mechanisms involved in the virus-insect interactions. In contrast, the genome of the fruit fly (Drosophila melanogaster) has been successfully sequenced, and it is used extensively as a model of molecular pathways due to the existence of powerful genetic technology. In this study, D. melanogaster is investigated as a model for the replication and tropism of BTV. Using reverse genetics, a modified BTV-1 that expresses the fluorescent mCherry protein fused to the viral nonstructural protein NS3 (BTV-1/NS3mCherry) was generated. We demonstrate that BTV-1/NS3mCherry is not only replication competent as it retains many characteristics of the wild-type virus but also replicates efficiently in D. melanogaster after removal of the bacterial endosymbiont Wolbachia pipientis by antibiotic treatment. Furthermore, confocal microscopy shows that the tissue tropism of BTV-1/NS3mCherry in D. melanogaster resembles that described previously for BTV in Culicoides. Overall, the data presented in this study demonstrate the feasibility of using D. melanogaster as a genetic model to investigate BTV-insect interactions that cannot be otherwise addressed in vector species. PMID- 22674992 TI - Cytotoxic T-lymphocyte escape mutations identified by HLA association favor those which escape and revert rapidly. AB - Identifying human immunodeficiency virus (HIV) immune escape mutations has implications for understanding the impact of host immunity on pathogen evolution and guiding the choice of vaccine antigens. One means of identifying cytotoxic-T lymphocyte (CTL) escape mutations is to search for statistical associations between mutations and host human leukocyte antigen (HLA) class I alleles at the population level. The impact of evolutionary rates on the strength of such associations is not well defined. Here, we address this topic using a mathematical model of within-host evolution and between-host transmission of CTL escape mutants that predicts the prevalence of escape mutants at the population level. We ask how the rates at which an escape mutation emerges in a host who bears the restricting HLA and reverts when transmitted to a host who does not bear the HLA affect the strength of an association. We consider the impact of these factors when using a standard statistical method to test for an association and when using an adaptation of that method that corrects for phylogenetic relationships. We show that with both methods, the average sample size required to identify an escape mutation is smaller if the mutation escapes and reverts quickly. Thus, escape mutations identified as HLA associated systematically favor those that escape and revert rapidly. We also present expressions that can be used to infer escape and reversion rates from cross-sectional escape prevalence data. PMID- 22674993 TI - Solution structure, conformational dynamics, and CD4-induced activation in full length, glycosylated, monomeric HIV gp120. AB - The gp120 subunit of the HIV Env glycoprotein is responsible for receptor interactions leading to viral entry and is a primary target for neutralizing antibodies. Most structural studies have focused on the heavily truncated, deglycosylated gp120 core, leaving fundamental aspects of the glycoprotein that are responsible for immune evasion and receptor-induced activation unresolved. Here we investigate full-length, glycosylated HIV gp120 in unliganded and CD4 bound forms by using small-angle X-ray scattering to visualize global structural reorganization and hydrogen/deuterium exchange to track changes in local conformational dynamics. The studies revealed unliganded full-length gp120 to be considerably more dynamic, particularly at the CD4 binding site, than suggested by previous studies of the subunit core alone. The large V1/V2 loops, previously unmapped, are positioned to mask the coreceptor binding site in an orientation that recapitulates that observed in the Env trimer. CD4 binding shifts V1/V2 to unmask the coreceptor binding site and triggers profound dynamic changes in gp120 spanning from the binding site to the gp41-interactive face of gp120. These findings provide further insights on the structural basis of Env antigenicity and immunogenicity and of allosteric effects upon receptor binding. PMID- 22674994 TI - Modulation of translation initiation efficiency in classical swine fever virus. AB - Modulation of translation initiation efficiency on classical swine fever virus (CSFV) RNA can be achieved by targeted mutations within the internal ribosome entry site (IRES). In this study, cDNAs corresponding to the wild-type (wt) or mutant forms of the IRES of CSFV strain Paderborn were amplified and inserted into dicistronic reporter plasmids encoding Fluc and Rluc under the control of a T7 promoter. The mutations were within domains II, IIId(1), and IIIf of the IRES. The plasmids were transfected into baby hamster kidney (BHK) cells infected with recombinant vaccinia virus vTF7-3, which expresses the T7 RNA polymerase. IRES mutants with different levels of IRES activity were identified and then introduced by homologous recombination into bacterial artificial chromosomes (BACs) containing CSFV Paderborn cDNA downstream of a T7 promoter. From the wt and mutant BACs, full-length CSFV RNA transcripts were produced in vitro and electroporated into porcine PK15 cells. Rescued mutant viruses were obtained from RNAs that contained mutations within domain IIIf which retained more than 75% of the wt translation efficiency. Sequencing of cDNA generated from these rescued viruses verified the maintenance of the introduced changes within the IRES. The growth characteristics of each rescued mutant virus were compared to those of the wt virus. It was shown that viable mutant viruses with reduced translation initiation efficiency can be designed and generated and that viruses containing mutations within domain IIIf of the IRES have reduced growth in cell culture compared to the wt virus. PMID- 22674995 TI - Hepatitis D virus isolates with low replication and epithelial-mesenchymal transition-inducing activity are associated with disease remission. AB - Clearance of hepatitis D virus (HDV) viremia leads to disease remission. Large hepatitis delta antigen (L-HDAg) has been reported to activate transforming growth factor beta, which may induce epithelial-mesenchymal transition (EMT) and fibrogenesis. This study analyzed serum HDV RNA "quasispecies" in HDV-infected patients at two stages of infection: before and after alanine aminotransferase (ALT) elevations. Included in the study were four patients who went into remission after ALT elevation and three patients who did not go into remission and progressed to cirrhosis or hepatocellular carcinoma. Full-length HDV cDNA clones were obtained from the most abundant HDV RNA species at the pre- and post ALT elevation stages. Using an in vitro model consisting of Huh-7 cells transfected with cloned HDV cDNAs, the pre- or post-ALT elevation dominant HDV RNA species were characterized for (i) their replication capacity by measuring HDV RNA and HDAg levels in transfected cells and (ii) their capacity to induce EMT by measuring the levels of the mesenchymal-cell-specific protein vimentin, the EMT regulators twist and snail, and the epithelial-cell-specific protein E cadherin. Results show that in patients in remission, the post-ALT elevation dominant HDV RNA species had a lower replication capacity in vitro and lower EMT activity than their pre-ALT elevation counterparts. This was not true of patients who did not go into remission. The expression of L-HDAg, but not small HDAg, increased the expression of the EMT-related proteins. It is concluded that in chronically infected patients, HDV quasispecies with a low replication capacity and low EMT activity are associated with disease remission. PMID- 22674996 TI - Influenza virus protein PB1-F2 inhibits the induction of type I interferon by binding to MAVS and decreasing mitochondrial membrane potential. AB - PB1-F2 is a small, 87- to 90-amino-acid-long protein encoded by the +1 alternate open reading frame of the PB1 gene of most influenza A virus strains. It has been shown to contribute to viral pathogenicity in a host- and strain-dependent manner, and we have previously discovered that a serine at position 66 (66S) in the PB1-F2 protein increases virulence of the 1918 and H5N1 pandemic viruses. Recently, we have shown that PB1-F2 inhibits the induction of type I interferon (IFN) at the level of the MAVS adaptor protein. However, the molecular mechanism for the IFN antagonist function of PB1-F2 has remained unclear. In the present study, we demonstrated that the C-terminal portion of the PB1-F2 protein binds to MAVS in a region that contains the transmembrane domain. Strikingly, PB1-F2 66S was observed to bind to MAVS more efficiently than PB1-F2 66N. We also tested the effect of PB1-F2 on the IFN antagonist functions of the polymerase proteins PB1, PB2, and PA and observed enhanced IFN inhibition by the PB1 and PB2 proteins in combination with PB1-F2 but not by the PA protein. Using a flow cytometry-based assay, we demonstrate that the PB1-F2 protein inhibits MAVS-mediated IFN synthesis by decreasing the mitochondrial membrane potential (MMP). Interestingly, PB1-F2 66S affected the MMP more efficiently than wild-type PB1 F2. In summary, the results of our study identify the molecular mechanism by which the influenza virus PB1-F2 N66S protein increases virulence. PMID- 22674997 TI - Naturally occurring swine influenza A virus PB1-F2 phenotypes that contribute to superinfection with Gram-positive respiratory pathogens. AB - A combination of viral, bacterial, and host factors contributes to the severity and overall mortality associated with influenza virus-bacterium superinfections. To date, the virulence associated with the recently identified influenza virus protein PB1-F2 has been largely defined using models of primary influenza virus infection, with only limited assessment in models of Streptococcus pneumoniae superinfection. Specifically, these studies have incorporated isogenic viruses that differ in the PB1-F2 expressed, but there is still knowledge to be gained from evaluation of natural variants derived from a nonhuman host species (swine). Using this rationale, we developed the hypothesis that naturally occurring viruses expressing variants of genes, like the PB1-F2 gene, can be associated with the severity of secondary bacterial infections. To test this hypothesis, we selected viruses expressing variants in PB1-F2 and evaluated outcomes from superinfection with three distinct Gram-positive respiratory pathogens: Streptococcus pneumoniae, Staphylococcus aureus, and Streptococcus pyogenes. Our results demonstrate that the amino acid residues 62L, 66S, 75R, 79R, and 82L, previously proposed as molecular signatures of PB1-F2 virulence for influenza viruses in the setting of bacterial superinfection, are broadly associated with enhanced pathogenicity in swine in a bacterium-specific manner. Furthermore, truncated PB1-F2 proteins can preferentially increase mortality when associated with Streptococcus pyogenes superinfection. These findings support efforts to increase influenza virus surveillance to consider viral genotypes that could be used to predict increased severity of superinfections with specific Gram-positive respiratory pathogens. PMID- 22674998 TI - Hepatitis C virus infection alters P-body composition but is independent of P body granules. AB - Processing bodies (P-bodies) are highly dynamic cytoplasmic granules conserved among eukaryotes. They are present under normal growth conditions and contain translationally repressed mRNAs together with proteins from the mRNA decay and microRNA (miRNA) machineries. We have previously shown that the core P-body components PatL1, LSm1, and DDX6 (Rck/p54) are required for hepatitis C virus (HCV) RNA replication; however, how HCV infection affects P-body granules and whether P-body granules per se influence the HCV life cycle remain unresolved issues. Here we show that HCV infection alters P-body composition by specifically changing the localization pattern of P-body components that are required for HCV replication. This effect was not related to an altered expression level of these components and could be reversed by inhibiting HCV replication with a polymerase inhibitor. Similar observations were obtained with a subgenomic replicon that supports only HCV translation and replication, indicating that these early steps of the HCV life cycle trigger the P-body alterations. Finally, P-body disruption by Rap55 depletion did not affect viral titers or HCV protein levels, demonstrating that the localization of PatL1, LSm1, and DDX6 in P-bodies is not required for their function on HCV. Thus, the HCV-induced changes on P-bodies are mechanistically linked to the function of specific P-body components in HCV RNA translation and replication; however, the formation of P-body granules is not required for HCV infection. PMID- 22674999 TI - Structural properties of the C terminus of vesicular stomatitis virus N protein dictate N-RNA complex assembly, encapsidation, and RNA synthesis. AB - The vesicular stomatitis virus (VSV) nucleoprotein (N) associates tightly with the viral genomic RNA. This N-RNA complex constitutes the template for the RNA dependent RNA polymerase L, which engages the nucleocapsid via its phosphoprotein cofactor P. While N and P proteins play important roles in regulating viral gene expression, the molecular basis of this regulation remains incompletely understood. Here we show that mutations in the extreme C terminus of N cause defects in viral gene expression. To determine the underlying cause of such defects, we examined the effects of the mutations separately on encapsidation and RNA synthesis. Expression of N together with P in Escherichia coli results predominantly in the formation of decameric N-RNA rings. In contrast, nucleocapsid complexes containing the substitution N(Y415A) or N(K417A) were more loosely coiled, as revealed by electron microscopy (EM). In addition, the N(EF419/420AA) mutant was unable to encapsidate RNA. To further characterize these mutants, we engineered an infectious cDNA clone of VSV and employed N-RNA templates from those viruses to reconstitute RNA synthesis in vitro. The transcription assays revealed specific defects in polymerase utilization of the template that result in overall decreased RNA quantities, including reduced amounts of leader RNA. Passage of the recombinant viruses in cell culture led to the accumulation of compensatory second-site mutations in close proximity to the original mutations, underscoring the critical role of structural features within the C terminus in regulating N function. PMID- 22675000 TI - FOXO3 regulates the CD8 T cell response to a chronic viral infection. AB - Chronic infections with viruses such as hepatitis B virus, hepatitis C virus, and HIV constitute a major global public health problem. Studies of chronic viral infections in humans and mice show that persistent antigenic stimulation induces dysregulation of T cell responses; virus-specific T cells either undergo clonal deletion or lose their ability to display the full spectrum of effector functions, a condition termed functional exhaustion. The ability to generate and retain sufficient numbers of functionally competent T cells, therefore, becomes vitally important in controlling chronic viral infections. Our understanding of the mechanisms governing T cell homeostasis during chronic viral infections, however, is poor. The phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway controls cell fate decisions in many cell types by modulating the activity of downstream effectors, including the FOXO family of transcription factors. We have observed dynamic, in vivo alterations in the phosphorylation levels of three key proteins (Akt, FOXO1/FOXO3 [FOXO1/3], and mammalian target of rapamycin [mTOR]) involved in this signaling cascade and have identified the transcription factor FOXO3 as a negative regulator of the magnitude and effector function of CD8 T cells during chronic lymphocytic choriomeningitis virus (LCMV) infection in mice. We report that ablation of FOXO3 in T cells reduced apoptosis, increased the abundance of polyfunctional virus-specific CD8 T cells, and improved viral control. Thus, FOXO3 is a promising candidate target for immunotherapies of chronic viral infection. PMID- 22675001 TI - A rare finding of multiple schwannomas in the epiglottis. PMID- 22675002 TI - Functional and symptom impacts of pediatric head and neck lymphatic malformations: developing a patient-derived instrument. AB - OBJECTIVE: Lymphatic malformations cause significant symptoms and functional deficits. Patients seek care for functional and symptomatic effects of their disease, but current disease burden and treatment outcome measures focus primarily on anatomy and histopathology. The authors describe disease impacts reported by patients and parents as a step toward more comprehensive disease burden assessments. STUDY DESIGN: Cross-sectional. SETTING: Children's hospital vascular anomaly clinic. SUBJECTS AND METHODS: Participants were recruited through a pediatric vascular anomaly clinic. A panel of senior pediatric otolaryngologists and an outcomes scientist developed interview questions based on clinical and research experience and available literature. The outcomes scientist conducted parent and adolescent interviews. The panel reviewed responses to define relevant items within functional domains. Participants rated impact on daily life for each domain. RESULTS: Thirty-one participants represented all 5 de Serres stages (mean [SD] age, 9 [6] years; n = 11 adolescents and 20 parents). Adolescents reported frequent sickness as the domain with greatest impact. Sleep was more affected in adolescents with higher stage lesions. Parents of younger children reported greatest impact on breastfeeding. For adolescents, lesion stage predicted perceived social stigma (controlling for age), whereas increasing age was associated with greater impact from swelling (controlling for stage). For parents, stage predicted breastfeeding impact (controlling for stage). CONCLUSION: This is the first detailed assessment of patient- and parent-reported functional and symptomatic impacts of head and neck lymphatic malformations. Both adolescent patients and parents of younger children reported significant symptom and functional effects of this disease. PMID- 22675003 TI - Functional connectivity during modulation of tinnitus with orofacial maneuvers. AB - OBJECTIVE: To determine changes in cortical neural networks as defined by resting state functional connectivity magnetic resonance imaging during voluntary modulation of tinnitus with orofacial maneuvers. STUDY DESIGN: Cross-sectional study. SETTING: Academic medical center. SUBJECTS AND METHODS: Participants were scanned during the maneuver and also at baseline to serve as their own control. The authors chose, a priori, 58 seed regions to evaluate previously described cortical neural networks by computing temporal correlations between all seed region pairs. Seed regions whose correlations significantly differed between rest and maneuver (P < .05, uncorrected) entered into a second-stage analysis of computing the correlation coefficient between the seed region and time courses in each of the remaining brain voxels. A threshold-free cluster enhancement permutation analysis evaluated the distribution of these correlation coefficients after transformation to Fisher z scores and registration to a surface-based reconstruction using Freesurfer. RESULTS: The median age for the 16 subjects was 54 years (range, 27-72 years), and all had subjective, unilateral or bilateral, nonpulsatile tinnitus for 6 months or longer. In 9 subjects who could voluntarily increase the loudness of their tinnitus, there were no significant differences in functional connectivity in any cortical networks. A separate analysis evaluated results from 3 patients who decreased the loudness of their tinnitus. Four subjects were excluded because of excessive motion in the scanner. CONCLUSION: The absence of significant differences in functional connectivity due to voluntary orofacial maneuvers that increased tinnitus loudness failed to confirm prior reports of altered cerebral blood flows during somatomotor behaviors. PMID- 22675004 TI - Multidisciplinary team approach in the management of tracheostomy patients. AB - OBJECTIVE: To examine whether the implementation of a multidisciplinary percutaneous tracheostomy team decreases complications, improves efficiency in patient care, and reduces length of stay and cost in patients undergoing percutaneous tracheostomy. STUDY DESIGN: Case series with planned data collection. SETTING: Urban, academic, tertiary care medical center. SUBJECTS AND METHODS: Patients who underwent a percutaneous tracheostomy in 2004 and 2008, before and after the formation of a multidisciplinary percutaneous tracheostomy team, were included in the study. Data for the study were retrieved from a tracheostomy database. Measured outcomes include complications, efficiency, length of stay, and cost. RESULTS: Complications such as airway bleeding and physiological disturbances decreased significantly in 2008 as compared with 2004. The percentage of patients who received a tracheostomy within 2 days increased from 42.3% to 92% (2004 vs 2008), showing improvement in efficiency of care. There was no significant difference between the groups in terms of infection rate, length of stay, or mortality. However, in a subanalysis, the length of stay was found to be decreased in patients whose primary diagnosis was a neurological disorder. Finally, despite the necessity of a hospital-based subsidy, the team approach yielded substantial financial benefit to the medical center. CONCLUSIONS: Airway bleeding, physiological disturbances, and efficiency of care improved after the institution of a multidisciplinary percutaneous tracheostomy team approach and may have a favorable impact on health care costs. PMID- 22675005 TI - Reducing disposable equipment waste for tonsillectomy and adenotonsillectomy cases. AB - Large amounts of waste in hospitals are generated in the operating rooms from disposable surgical supplies. Tonsillectomy/adenotonsillectomy (T&A) cases use many disposable supplies that are not recyclable. It is critical to reduce disposable waste, as such waste directly affects the environment and increases health care costs. The authors noticed a difference between the number of disposable items prepared, available, but almost never used, for each tonsillectomy case between a children's hospital setting and a university ambulatory surgery center setting. The aims were the following: (1) identify what disposable medical supplies were unnecessarily opened for each case, (2) eliminate all disposable medical waste that was not critical to the case in both settings, and (3) determine the cost reduction at both hospital and surgery center facilities by revising the current disposable instruments/supplies pulled for tonsillectomy cases. The authors report projected cost savings and reduction in waste for one children's hospital and nationally based on their waste reduction. PMID- 22675006 TI - Pushing out the limits of electrical stimulation. A case study in the aggressive use of an alternative to voluntary exercise. AB - Recent advances in neuromuscular electrical stimulation (NMES) suggest that sophisticated techniques can exercise and train people aerobically. However, the limits of this exercise modality would be of interest to sportspeople, trainers and rehabilitation experts. Additionally, there are physical and other barriers which prevent many from undertaking aggressive voluntary exercise. Maximum voluntary and peak NMES efforts were assessed for 1) maximal heart rate and oxygen consumption, 2) excess postexercise oxygen consumption (EPOC), 3) lactate and 4) time-to-fatigue while exercising at 65% of predicted maximal heart rate (maximum voluntary versus peak NMES efforts). Heart rates: 195 bpm and 194 bpm; Oxygen consumption: 52 ml/kg/min and 39 ml/kg/min. EPOC: 110.5 kcal and 96.5 kcal; Lactate: 15.0 mmol/l and 15.3 mmol/l; Time-to-fatigue: 4 h and over 6 h. Sophisticated NMES compares well to voluntary exercise with potential applications for sportspeople and some who cannot exercise due to disease or injury. PMID- 22675007 TI - Tuberculous pericarditis associated with hoarseness of voice due to left recurrent laryngeal nerve paralysis. AB - A 16-years-old Egyptian girl presented with massive pericardial effusion, fever, weight loss and hoarseness of voice. Laryngoscopy showed left vocal cord paralysis. Chest CT revealed pericardial effusion, amalgamated mediastinal lymph nodes and clear lung fields. Pericardial fluid analysis revealed a lymphocytic exudate with high adenosine deaminase enzyme level, negative stains and cultures for bacteria and fungi. Despite a negative nucleic acid test for tuberculosis; antituberculous and corticosteroids therapies resulted in resolution of pericardial effusion after 3 weeks but hoarseness of voice persisted. Few cases of vocal cord paralysis with tuberculous mediastinal lymphadenopathy were reported in English literature. PMID- 22675008 TI - Short duration respiratory illness with abducens palsy in a young man. AB - Acute onset of diplopia associated with high-grade fever, sore throat and cough without features of raised intracranial tension in a young patient is an uncommon presentation. A diagnosis of abducent nerve palsy due to pontine tuberculoma associated with miliary tuberculosis was made based on sputum examination, chest x-ray and MRI. On diagnosis, monocular patching of the left eye was performed to avoid diplopia and primary antitubercular drugs with systemic steroids were given. An unfortunate 48 h delay in starting the antitubercular treatment likely decreased the probability of survival. PMID- 22675009 TI - Painless nodules over joints with ulceration. PMID- 22675010 TI - A rare case of non-insulinoma pancreatic hypoglycaemia syndrome (niphs) in an adult due to localised islet cell hyperplasia-successfully managed by enucleation. AB - Persistent hyperinsulinemic hypoglycaemia is caused most commonly by an insulinoma in adults or by nesidioblastosis in neonates. In adults, localised islet cell hyperplasia is a rare disorder characterised by localised proliferation of islet cells. The authors present the case of a previously healthy non-obese middle aged female with new-onset severe hypoglycaemia. Laboratory findings confirmed a case of hyperinsulinemic hypoglycaemia. Endoscopic ultrasonography, intra-arterial calcium stimulation test and intraoperative ultrasonography showed a lesion in the uncinate process that was enucleated. Rest of the pancreas was normal. Histological examination and immunostaining of the resected tissue revealed pancreatic tissue with maintained acinar pattern consistent with diagnosis of localised islet cell hyperplasia. The patient did not have further episodes of hypoglycaemia following the procedure. Localised islet cell hyperplasia with such a very high insulin level is exceedingly rare in adult populations and not reported in literature. This diagnosis cannot be easily made through routine diagnostic laboratory or radiological procedures and likely requires a histological diagnosis. Management of this rare entity is by enucleation. PMID- 22675011 TI - Statin resistant dyslipidemia in a patient treated with amiodarone. AB - The authors describe a patient treated with amiodarone presented with high low density lipoprotein cholesterol (LDL-C) levels who did not respond to treatment with a statin. Both amiodarone and amiodarone induced hypothyroidism influence the synthesis of LDL-receptor which may explain the lack of effect of statin. This was confirmed by normalisation of LDL-C upon discontinuation of amiodarone and treatment with thyroxine. PMID- 22675012 TI - Life-threatening retro-pharyngeal bleed in a case of systemic lupus erythematosus -an uncommon but important evil of a common disease. AB - Acquired inhibitors of coagulation are antibodies that interfere with the coagulation system either by functional inhibition of the activity of clotting factors or by their increased clearance from the plasma. They can be idiopathic or seen in various physiologic (pregnancy and postpartum) or pathologic states (systemic lupus erythematosus (SLE), malignancies, rheumatoid arthritis) and can result in a variety of haemorrhagic sequelae. SLE can be associated with antibodies to multiple clotting factors and bleeding though rare can be an important haematologic manifestation with life-threatening consequences in these patients. PMID- 22675013 TI - Binder's syndrome. AB - Binder syndrome or maxillonasal dysplasia is an uncommon developmental anomaly affecting primarily the anterior part of the maxilla and nasal complex. The characteristic findings are a failure of development in the premaxillary area with associated deformities of the nasal skeleton and the overlying soft tissues. Affected individuals typically have an unusually flat, underdeveloped midface (midfacial hypoplasia), with an abnormally short nose and flat nasal bridge, underdeveloped upper jaw, relatively protruding lower jaw and/or a 'reverse overbite' (or class III malocclusion). A 16-year-old female reported to clinic with chief complaint of facial deformity, on examination patient had classical feature of maxillonasal dysplasia. A brief review of the condition and the proposed multi-disciplinary treatment plan is discussed. PMID- 22675014 TI - Difficult to control asthma in the patient with pseudoachondroplasia. AB - Pseudoachondroplasia (PsA) is a type of short-limbed dwarfism resulting from mutations in the cartilage oligomeric matrix protein gene. Skeletal involvement in the PsA is well-described but there are not any published cases reporting airways involvement. The authors present a case of a female with the PsA and congenital anomalies of the respiratory tract resulting in the tracheobronchomalacia and a difficult to control asthma. PMID- 22675016 TI - Vibration therapy of the plantar fascia improves spasticity of the lower limbs of a patient with fetal-type Minamata disease in the chronic stage. AB - The authors present a novel treatment for spasticity using a hand-held vibration massager. A fetal-type Minamata disease patient showing spasticity of lower limbs had direct application of vibratory stimuli to the right plantar fascia and to the left hamstring. After the treatment for 1 year, the Modified Ashworth Scale (MAS) of the lower limbs was improved from three (right > left) to two (right < left). After then, direct application of the same method with the left plantar fascia improved the MAS of the left lower limb to two (right = left). The increased deep tendon reflexes had diminished and markedly positive Babinski's sign had also decreased to slightly positive on both sides. This method is so simple that patients can treat themselves at home. The authors think that direct application of vibratory stimuli to the plantar fascia is valuable to patients with neurologic disorders, particularly those who cannot receive more invasive treatments. PMID- 22675015 TI - Right abdominal mass in a 2 year-old child. AB - The authors report a case of a wandering spleen presenting as a right lower quadrant abdominal mass, 2 years post a transabdominal left diaphragmatic hernia repair in a 2-year-old child with a congenital diaphragmatic hernia. The wandering spleen was fixed laparoscopically in an extraperitoneal pouch. PMID- 22675017 TI - Chronic meningitis: a diagnostic challenge highlighted in a case of cryptococcal meningoencephalitis in an apparently immunocompetent older woman. AB - Chronic meningitis can be difficult to diagnose. The authors report the case of an older Caucasian lady, with no underlying immunocompromising factors, who presented with a 2 month history of confusion. Due to the non-specific symptoms on presentation, a diagnosis was only obtained after a repeat CT scan of the brain, which showed hydrocephalus. Subsequent cerebrospinal fluid analysis showed biochemical abnormalities and Cryptococcus neoformans on staining. PMID- 22675018 TI - Acute gastric volvulus: an uncommon complication of a hiatus hernia. AB - An 80-year-old male patient with a history of a hiatus hernia presented with acute abdominal pain and vomiting. CT of his abdomen revealed extraluminal free gas consistent with a perforation. He had a large hiatus hernia. The subdiaphragmatic portion of the stomach was distended and adopted a more transverse lie. The radiological findings were in keeping with acute gastric volvulus with secondary ischaemic complications. Acute gastric volvulus is an abnormal rotation of the stomach resulting in complete obstruction. It is a surgical emergency and does not always present in its classical form. Clinicians should be mindful of this diagnosis in patients presenting with an acute surgical abdomen, especially if the presentation is non-specific, as delays in diagnosis are associated with significant morbidity and mortality. PMID- 22675019 TI - Ellis van Creveld syndrome--a report of two siblings. AB - Chondro-ectodermal dysplasia is a rare autosomal recessive disorder which affects the ectodermal, mesodermal and endodermal derivatives. There are numerous conditions reported under this title which include Ellis van Creveld syndrome. The oral findings include multiple gingivolabial frena, dental abnormality, malocclusion and hypodontia. The diagnosis of Ellis van Creveld syndrome is based on the presence of oral mucosal changes like notching of the lower alveolus, fusion of the upper lip and gingival mucosa; dental changes like oligodontia, conical shape of anterior teeth and occasional presence of neonatal teeth. The authors report a rare case of Ellis van Creveld syndrome occurring among two siblings with oral mucosal, dental and skeletal abnormalities. PMID- 22675020 TI - Head trauma by captive bolt gun. AB - An 80 year-old former cattle-breeder committed suicide with a captive bolt gun. He was transmitted unconscious to emergency department. He had a large penetrating wound in right temporal area. Lateral radiograph of skull revealed a large rounded bony defect. CT verified a large rounded entry site and bony defect at the right pterion. It disclosed a wide, zonal-like haemorrhagic wound canal bearing intraparenchymal bony fragments at its end with no associated metallic fragments. Subarachnoid haemorrhage with bilateral subepidural hematomas and significant brain oedema was demonstrated. PMID- 22675021 TI - An increasingly notorious mimicker of testicular tumours; crossing borders. AB - Data from the WHO state that up to 85% of cases of human schistosomiasis are from Africa. The common sites of this parasitic infection are the intestine and bladder. Testicular schistosomiasis is extremely rare but the number of reported cases worldwide has doubled over the past decade. The authors report a case of testicular schistosomiasis of a Myanmar immigrant in Malaysia who presented with a 6-month history of progressively enlarging left testicular swelling. His biochemical markers and cultures were not suggestive of an ongoing infection. Hence, a testicular malignancy was strongly suspected, for which, he underwent a left orchidectomy. Our clinical suspicion was proven wrong when the histopathology of the removed left testis revealed schistosomal eggs with granulamatous tissue formation. Subsequently, the patient was treated with praziquantel. PMID- 22675022 TI - A pain in the neck. AB - A 21-year-old man presented to the emergency department with pain and swelling to the right side of his neck and chest wall with associated shortness of breath. Two days earlier, while playing football, he had been involved in a minor collision with another player where he was struck on the right side of his head, but had managed to continue playing. On examination, the patient had extensive cervical surgical emphysema. There were no further positive findings on respiratory and general examination. A chest x-ray demonstrated no rib or clavicular fractures and no pneumothorax. Therefore, a CT was undertaken to ascertain the cause of the surgical emphysema. This demonstrated a pneumomediastinum, pneumopericardium and extradural air in the spinal column in addition to the subcutaneous air. The CT identified no bony trauma and no other injuries. The symptoms resolved spontaneously and follow-up radiography, 9 days later, showed no residual air. PMID- 22675023 TI - Whatever is willed will be: a temporal asymmetry in attributions to will. AB - Why do people neglect or underweight their past failures when thinking about their prospects of future success? One reason may be that people think of the past and future as guided by different causal forces. In seven studies, the authors demonstrate that people hold asymmetric beliefs about the impact of an individual's will on past versus future events. People consider the will to be a more potent determinant of future events than events that happened in the past. This asymmetry holds between- and within-subjects, and generalizes beyond undergraduate populations. The authors contend that this asymmetry contributes to the tendency for people to remain confident about their future performance in domains in which they have largely failed in the past. This research thus contributes to a growing body of literature exploring how thoughts about events in the past differ from thoughts about the same events set in the future. PMID- 22675024 TI - Insights into structural and regulatory roles of Sec16 in COPII vesicle formation at ER exit sites. AB - COPII-coated buds are formed at endoplasmic reticulum exit sites (ERES) to mediate ER-to-Golgi transport. Sec16 is an essential factor in ERES formation, as well as in COPII-mediated traffic in vivo. Sec16 interacts with multiple COPII proteins, although the functional significance of these interactions remains unknown. Here we present evidence that full-length Sec16 plays an important role in regulating Sar1 GTPase activity at the late steps of COPII vesicle formation. We show that Sec16 interacts with Sec23 and Sar1 through its C-terminal conserved region and hinders the ability of Sec31 to stimulate Sec23 GAP activity toward Sar1. We also find that purified Sec16 alone can self-assemble into homo oligomeric complexes on a planar lipid membrane. These features ensure prolonged COPII coat association within a preformed Sec16 cluster, which may lead to the formation of ERES. Our results indicate a mechanistic relationship between COPII coat assembly and ERES formation. PMID- 22675025 TI - Nuclear hormone receptor corepressor promotes esophageal cancer cell invasion by transcriptional repression of interferon-gamma-inducible protein 10 in a casein kinase 2-dependent manner. AB - Aberrant expression of casein kinase 2 (CK2) is associated with tumor progression; however, the molecular mechanism by which CK2 modulates tumorigenesis is incompletely understood. In this paper, we show that CK2alpha phosphorylates the C-terminal domain of the nuclear receptor corepressor (NCoR) at Ser-2436 to stabilize the NCoR against the ubiquitin-dependent proteasomal degradation pathway. Importantly, NCoR promoted the invasion of esophageal cancer cells in a CK2-dependent manner. By using cyclic DNA microarray analysis, we identified CXCL10/IP-10 as a novel CK2alpha-NCoR cascade-regulated gene. The depletion of both NCoR and HDAC3 commonly derepressed IP-10 transcription, demonstrating the functional engagement of the NCoR-HDAC3 axis in IP-10 transcriptional repression. Furthermore, chromatin immunoprecipitation assays showed that c-Jun recruits NCoR-HDAC3 corepressor complexes to the (AP1 site of IP-10, leading to histone hypoacetylation and IP-10 down-regulation. Collectively these data suggest that the CK2alpha-NCoR cascade selectively represses the transcription of IP-10 and promotes oncogenic signaling in human esophageal cancer cells. PMID- 22675026 TI - Cot/tpl2-MKK1/2-Erk1/2 controls mTORC1-mediated mRNA translation in Toll-like receptor-activated macrophages. AB - Cot/tpl2 is the only MAP3K that activates MKK1/2-Erk1/2 in Toll-like receptor activated macrophages. Here we show that Cot/tpl2 regulates RSK, S6 ribosomal protein, and 4E-BP phosphorylation after stimulation of bone marrow-derived macrophages with lipopolysaccharide (LPS), poly I:C, or zymosan. The dissociation of the 4E-BP-eIF4E complex, a key event in the cap-dependent mRNA translation initiation, is dramatically reduced in LPS-stimulated Cot/tpl2-knockout (KO) macrophages versus LPS-stimulated wild-type (Wt) macrophages. Accordingly, after LPS activation, increased cap-dependent translation is observed in Wt macrophages but not in Cot/tpl2 KO macrophages. In agreement with these data, Cot/tpl2 increases the polysomal recruitment of the 5' TOP eEF1alpha and eEF2 mRNAs, as well as of inflammatory mediator gene-encoding mRNAs, such as tumor necrosis factor alpha (TNFalpha), interleukin-6 (IL-6), and KC in LPS-stimulated macrophages. In addition, Cot/tpl2 deficiency also reduces total TNFalpha, IL-6, and KC mRNA expression in LPS-stimulated macrophages, which is concomitant with a decrease in their mRNA half-lives. Macrophages require rapid fine control of translation to provide an accurate and not self-damaging response to host infection, and our data show that Cot/tpl2 controls inflammatory mediator gene encoding mRNA translation in Toll-like receptor-activated macrophages. PMID- 22675027 TI - Myosin 1E coordinates actin assembly and cargo trafficking during clathrin mediated endocytosis. AB - Myosin 1E (Myo1E) is recruited to sites of clathrin-mediated endocytosis coincident with a burst of actin assembly. The recruitment dynamics and lifetime of Myo1E are similar to those of tagged actin polymerization regulatory proteins. Like inhibition of actin assembly, depletion of Myo1E causes reduced transferrin endocytosis and a significant delay in transferrin trafficking to perinuclear compartments, demonstrating an integral role for Myo1E in these actin-mediated steps. Mistargeting of GFP-Myo1E or its src-homology 3 domain to mitochondria results in appearance of WIP, WIRE, N-WASP, and actin filaments at the mitochondria, providing evidence for Myo1E's role in actin assembly regulation. These results suggest for mammalian cells, similar to budding yeast, interdependence in the recruitment of type I myosins, WIP/WIRE, and N-WASP to endocytic sites for Arp2/3 complex activation to assemble F-actin as endocytic vesicles are being formed. PMID- 22675028 TI - Cyclic AMP regulates formation of mammary epithelial acini in vitro. AB - Epithelial cells form tubular and acinar structures notable for a hollow lumen. In three-dimensional culture utilizing MCF10A mammary epithelial cells, acini form due to integrin-dependent polarization and survival of cells contacting extracellular matrix (ECM), and the apoptosis of inner cells of acini lacking contact with the ECM. In this paper, we report that cyclic AMP (cAMP)-dependent protein kinase A (PKA) promotes acinus formation via two mechanisms. First, cAMP accelerates redistribution of alpha6-integrin to the periphery of the acinus and thus facilitates the polarization of outer acinar cells. Blocking of alpha6 integrin function by inhibitory antibody prevents cAMP-dependent polarization. Second, cAMP promotes the death of inner cells occupying the lumen. In the absence of cAMP, apoptosis is delayed, resulting in perturbed luminal clearance. cAMP-dependent apoptosis is accompanied by a posttranscriptional PKA-dependent increase in the proapoptotic protein Bcl-2 interacting mediator of cell death. These data demonstrate that cAMP regulates lumen formation in mammary epithelial cells in vitro, both through acceleration of polarization of outer cells and apoptosis of inner cells of the acinus. PMID- 22675029 TI - Parallel relaxation of stringent RNA recognition in plant and mammalian L1 retrotransposons. AB - L1 elements are mammalian non-long terminal repeat retrotransposons, or long interspersed elements (LINEs), that significantly influence the dynamics and fluidity of the genome. A series of observations suggest that plant L1-clade LINEs, just as mammalian L1s, mobilize both short interspersed elements (SINEs) and certain messenger RNA by recognizing the 3'-poly(A) tail of RNA. However, one L1 lineage in monocots was shown to possess a conserved 3'-end sequence with a solid RNA structure also observed in maize and sorghum SINEs. This strongly suggests that plant LINEs require a particular 3'-end sequence during initiation of reverse transcription. As one L1-clade LINE was also found to share the 3'-end sequence with a SINE in a green algal genome, I propose that the ancestral L1 clade LINE in the common ancestor of green plants may have recognized the specific RNA template, with stringent recognition then becoming relaxed during the course of plant evolution. PMID- 22675030 TI - Resolution of ischemia with beta-blocker in a patient with anomalous right coronary artery. AB - Anomalous origin of right coronary artery (RCA) has been associated with angina, myocardial infarction and sudden death. Often these patients are referred for surgery. However, long-term beta-blocker therapy instead of surgery has been used in some cases with success. The authors report a case of anomalous RCA where resolution of ischemia with beta-blocker was objectively demonstrated on serial stress testing. PMID- 22675031 TI - Adamantinoma of the tibia and fibula with pulmonary metastasis: an unusual presentation. AB - Adamantinoma is a rare tumour of long bones, representing less than 1% of them. Adamantinoma commonly occurs in the tibia. It is locally aggressive and recurrences are uncommon after resection. Metastases have been reported in less than 10% of cases. The most common radiographic appearance is multiple sharply demarcated radiolucent lesions surrounded by areas of dense sclerotic bone. The authors report a patient who developed pulmonary metastasis 1 year after complete resection of primary neoplasm. PMID- 22675032 TI - Overzealous cardiac massage leading to unintentional infant death. AB - The case of an 18-month child is presented, with a picture demonstrating the thoracic trauma, caused from a hand pressure movement, perpetrated with an open right palm, in an attempt to perform an external cardiac massage. The child showed continuous episodes of 'crying spells' that the medical staff considered as benign, but an overprotective and mentally unstable mother kept on violently 'resuscitating' her son during such episodes. The last episode was characterised with a strenuous massage of the thoracic wall, causing evident bruises and leading to a cardiac contusion. The mother who perpetrated the trauma was sentenced for manslaughter, after the accidental character of the event, as well as the severity of her family situation and the precarious living environment of a socially abandoned single-acting parent, were all taken into account. The particular psychopathology of the care giver (mother) and the characteristics of the inflicted thoracic blow are described. PMID- 22675033 TI - Long-term effectiveness of dobesilate in the treatment of papulopustular rosacea. AB - This case report is a representative example from a study directed to assess the long-term clinical benefit of dobesilate in rosacea in five enrolled papulopustular rosacea patients with several years of disease, treated topically with 5% potassium dobesilate cream for 3 weeks. The patient suffered papulopustular rosacea for more than 10 years, during which she received topical metronidazole and azelaic acid, and systemic doxycycline therapies without satisfactory improvement. Dobesilate treatment promoted improvement of rosacea symptoms and signs. Two years after treatment the patient still shows a good facial cosmesis. PMID- 22675034 TI - Pott's puffy tumour by Streptoccocus intermedius a rare complication of sinusitis. PMID- 22675035 TI - Is heel prick as safe as we think? AB - Purulent lymphadenitis is rare in newborn and is associated with prematurity and invasive procedure. Neonatal staphylococcal infections due to skin interruption during intramuscular vitamin K administration and national metabolic screening programme (heel prick or Guthrie card test) have been already previously described. This is a report of a premature infant who developed an inguinal adenitis as a result of late complications from heel pricks. The diagnosis was made on clinical grounds and confirmed by ultrasound scans. Staphylococcus aureus was isolated. Bacteremia did not occur and the lymphadenitis had a complete resolution with antimicrobial therapy. The heel prick is a well-established procedure in neonatal practice, nevertheless it is not risk-free. The attention to signs of infections is important to avoid complications such as purulent lymphadenitis, abscess formation and septicemia. Best practice prevention and control in minimising the risk of infections are the most important intervention to prevent this complication. PMID- 22675036 TI - Papilloedema due to Chiari I malformation. AB - The Chiari I malformation is a congenital abnormality characterised by downward displacement of the cerebellar tonsils through the foramen magnum into the cervical spine. It presents clinically most often in young adult women. Known ocular manifestations linked to Chiari I consist primarily of oculomotor paresis with cranial nerve VI palsy and convergence/divergence abnormalities. Papilloedema is a rare manifestation of Chiari I with a clinical presentation often similar to that of idiopathic intracranial hypertension. To highlight this unusual complication, the authors report a 64-year-old female who developed papilloedema as the only presenting neurological symptom resulting from a Chiari I malformation. PMID- 22675037 TI - Tubercular dactylitis and multifocal osteoarticular tuberculosis--two rare cases of extrapulmonary tuberculosis. AB - Involvement of small bones of hand and feet leading to tuberculous dactylitis involvement is a rare presentation of extrapulmonary tuberculosis. Even rarer is the association of tuberculous dactylitis with multifocal skeletal involvement, even in countries like ours, where tuberculosis is endemic. The authors report two cases, one of tuberculous dactylitis in a 55-year-old male and another of multifocal skeletal tuberculosis in a 4-year-old male. Both the patients were effectively treated with antitubercular drugs. PMID- 22675038 TI - Adult onset startle epilepsy. AB - A 45-year-old gentleman presented for classification of spells precipitated by startle. During these spells, he would briefly lose awareness, develop tonic stiffening of his extremities and fall. He had previously been diagnosed with paroxysmal kinesogenic dyskinesia and treated unsuccessfully with clonazepam, levetiracetam and carbamazepine. The patient was admitted for prolonged video EEG monitoring, during which numerous spells induced by startle were captured. His EEG revealed brief, fast beta activity in the midline central head region during each spell consistent with startle epilepsy. The present case demonstrates that startle epilepsy can rarely be diagnosed in adults; typically seizure onset in this condition is during infancy to childhood. Our patient's ictal EEG further implicates mesial structures in the generation of startle-provoked seizures. Although our patient continued to have startle-provoked seizures at last follow up, his improvement on lamotrigine supports observations that this anticonvulsant can reduce seizure frequency and resulting morbidity. PMID- 22675039 TI - Intracranial dural arterio-venous fistula presenting with progressive myelopathy. AB - Spinal dural arterio-venous fistula (DAVF) is rare and usually involves the thoracic segments. The classical presentation is a slowly progressive ataxia. Clinical presentation of intracranial DAVF depends on the site of the DAVF, as well as the vessels involved. Patients may present with pulsatile tinnitus, occipital bruit, headache, dementia, visual impairment as well as neurological deterioration distant from the DAVF as a result of venous hypertension and cortical haemorrhage. The authors present a rare case of progressive myelopathy secondary to an intracranial DAVF. PMID- 22675040 TI - Bilateral shoulder fracture, dislocation and replacement: a first presentation of epilepsy. PMID- 22675041 TI - Cotargeting stress-activated Hsp27 and autophagy as a combinatorial strategy to amplify endoplasmic reticular stress in prostate cancer. AB - Hsp27 is a stress-activated multifunctional chaperone that inhibits treatment induced apoptosis and causes treatment resistance in prostate and other cancers. We previously showed that targeted suppression of Hsp27 sensitizes cancer cells to hormone and chemotherapy. However, mechanisms by which Hsp27 confers cell treatment resistance are incompletely defined. Here, we report that Hsp27 protects human prostate cancer cells against proteotoxic stress induced by proteasome inhibition, and that Hsp27 silencing using siRNA or antisense (OGX 427) induced both apoptosis and autophagy through mechanisms involving reduced proteasome activity and induction of endoplasmic reticulum (ER) stress. We found that autophagy activation protected against ER stress-induced cell death, whereas inhibition of autophagy activation following Hsp27 silencing using either pharmacologic inhibitors or atg3 silencing enhanced cell death. Importantly, cotargeting Hsp27 and autophagy by combining OGX-427 with the autophagy inhibitor, chloroquine, significantly delayed PC-3 prostate tumor growth in vivo. These findings identify autophagy as a cytoprotective, stress-induced adaptive pathway, activated following disruption of protein homeostasis and ER stress induced by Hsp27 silencing. Combinatorial cotargeting cytoprotective Hsp27 and autophagy illustrates potential benefits of blocking activation of adaptive pathways to improve treatment outcomes in cancer. PMID- 22675042 TI - Inhibition of dendritic cell maturation by the tumor microenvironment correlates with the survival of colorectal cancer patients following bevacizumab treatment. AB - Development of bevacizumab has improved survival in colorectal cancer, however, currently there are no biomarkers that predict response to bevacizumab and it is unknown how it influences the immune system in colorectal cancer patients. Dendritic cells are important for the induction of an antitumor immune response; however tumors are capable of disabling dendritic cells and escaping immune surveillance. The aim of this study was to assess the numbers of CD11c+ cells infiltrating tumor tissue and to examine the effects of tumor conditioned media (TCM) and bevacizumab conditioned media (BCM) on dendritic cell maturation and correlate our findings with patient survival. colorectal cancer explant tissues were cultured with or without bevacizumab, to generate BCM and TCM, which were used to treat dendritic cells. CD80, CD86, CD83, CD54, HLA-DR, and CD1d expression was measured by flow cytometry. Interleukin (IL)-10 and IL-12p70 were measured by ELISA. The Cox proportional hazards model was used to associate survival with dendritic cell inhibition. TCM and BCM inhibited lipopolysaccharide (LPS)-induced dendritic cell maturation and IL-12p70 secretion (P < 0.0001), while increasing IL-10 secretion (P = 0.0033 and 0.0220, respectively). Inhibition of LPS-induced CD1d (P = 0.021, HR = 1.096) and CD83 (P = 0.017, HR = 1.083) by TCM and inhibition of CD1d (P = 0.017, HR = 1.067), CD83 (P = 0.032, HR = 1.035), and IL-12p70 (P = 0.037, HR = 1.036) by BCM was associated with poor survival in colorectal cancer patients. CD11c expression was elevated in tumor tissue compared with normal tissue (P < 0.001), but this did not correlate with survival. In conclusion, TCM and BCM inhibit dendritic cells, and this inhibition correlates with survival of colorectal cancer patients receiving bevacizumab. PMID- 22675043 TI - Seminal plasma microRNAs: potential biomarkers for spermatogenesis status. AB - MicroRNAs (miRNAs) are small non-coding RNAs (18-25 nt), playing important regulatory roles via interaction with cellular messenger RNAs. The altered expression of miRNAs in specific tissues has been associated with diseases such as cancer and diabetes. We examined the presence of two selected miRNAs (miR-19b and let-7a) in human seminal plasma from fertile men and idiopathic infertile patients with oligozoospermia and non-obstructive azoospermia (NOA) using quantitative real-time PCR. We detected miRNAs in the seminal plasma of humans. The levels of miRNAs in the seminal plasma were reproducible in repeat samples from the same individuals. In addition, we examined the expression patterns of two selected miRNAs in 96 idiopathic infertile males (48 oligozoospermia and 48 NOA) and 48 fertile controls. Another 48 individuals of each group were used for verification. Our data showed that the expression levels of these two miRNAs in the seminal plasma significantly increased in idiopathic infertile males with NOA compared with fertile controls, whereas the expression levels were similar between idiopathic infertile males with oligozoospermia and fertile controls. In conclusion our results indicate that the expression of miR-19b and let-7a in the seminal plasma are reproducible and stable. Aberrant over-expression levels of miR-19b and let-7a may be an indicator of spermatogenic failure. PMID- 22675044 TI - A new species of Trichia from Australia. AB - A new species of Trichia (myxomycetes) was collected during surveys for myxomycetes carried out in Nothofagus cunninghamii forests in western Tasmania in May 2008 and a similar survey carried out in a N. morrei forest in New South Wales in May 2009. This new species, T. brimsiorum, is described and illustrated. It resembles T. decipiens in overall shape and size of the sporocarps but has smaller spores and the ornamentation of the capillitium is different. PMID- 22675045 TI - Zymoseptoria ardabiliae and Z. pseudotritici, two progenitor species of the septoria tritici leaf blotch fungus Z. tritici (synonym: Mycosphaerella graminicola). AB - Zymoseptoria is a newly described genus that includes the prominent wheat pathogen Zymoseptoria tritici (synonyms Mycosphaerella graminicola and Septoria tritici). Studies indicated that the center of origin of Z. tritici is in the Middle East where this important pathogen emerged during the domestication of wheat. Several Zymoseptoria species have been found on uncultivated grasses in the Middle East, and in this article we describe two new Zymoseptoria species from Iran. These species, isolated from Elymus repens, Dactylis glomerata and Lolium perenne, are named Z. ardabiliae and Z. pseudotritici. Both species were identified by means of morphological characteristics and phylogenetic analyses of a seven-gene DNA dataset. These taxa comprise some of the closest known relatives of the wheat pathogen Z. tritici, confirming the reported close phylogenetic relationship between Z. tritici and Z. pseudotritici. PMID- 22675046 TI - Fusarium tupiense sp. nov., a member of the Gibberella fujikuroi complex that causes mango malformation in Brazil. AB - Fusarium tupiense, the main causal agent of mango malformation in Brazil, is described through a combination of morphological, biological and molecular markers. This new species belongs to the Gibberella fujikuroi species complex (GFSC) and has an anamorph morphologically similar to Fusarium mangiferae and F. sterilihyphosum. F. tupiense can be differentiated from other species in the G. fujikuroi species complex on the basis of sexual crosses, amplified fragment length polymorphism (AFLP) markers and partial sequences of the tef1 and tub2 genes. Female fertility for field isolates of F. tupiense appears to be low. PCR with primers specific for the mating type (MAT) alleles and sexual crosses identified this species as heterothallic with two idiomorphs. Female-fertile tester strains were developed for the identification of field strains of this species through sexual crosses. PMID- 22675047 TI - Phylogenetic placement of the genus Anhellia and the description of A. nectandrae sp. nov. AB - The phylogenetic position of a new species of Anhellia (Myriangiales) was investigated by analysis of nucleotide sequences of ribosomal large subunit (LSU) and ITS regions. The new sequence was aligned with 28 sequences obtained from GenBank, including four species of Davidiellaceae (Capnodiales) used as outgroup. This study is the first attempt to resolve the placement of the genus Anhellia within Myriangiales. The genus Anhellia was strongly supported in Myriangiaceae by phylogenetic analyses. In addition, A. nectandrae sp. nov., collected on Nectandra rigida from a fragment of Atlantic forest in Brazil, is described, illustrated and a table with morphological features to all known Anhellia species is provided. PMID- 22675048 TI - Thoreauomyces gen. nov., Fimicolochytrium gen. nov. and additional species in Geranomyces. AB - Powellomycetaceae (Spizellomycetales) contain a diverse group of exogenously developing chytrids found by baiting water preparations of soils and manure with pollen. A previous molecular phylogenetic study indicated that some lineages within this family represent undescribed genera and species. Description of genera within the Spizellomycetales traditionally has relied on ultrastructural characters of zoospores, whereas species have been based on thallus development and morphology. We analyzed Powellomycetaceae chytrids that had not yet had ultrastructural and thallus morphologies determined. Because these chytrids vary little morphologically, we used a linear discriminant function analysis of thallus characters to determine features most useful for separating species when grown in pure culture on identical media. Zoosporic ultrastructures of two groups of isolates differed from those of the two described genera in the family, and we describe the new genera Thoreauomyces with one new species and Fimicolochytrium with two new species. Also, we describe three new species within Geranomyces. Linear discriminant function analysis, although helpful for determining more stable morphological characters, was not completely accurate in assigning chytrids to the correct genus or species, thus emphasizing the importance of molecular characters for identifying these taxa. PMID- 22675049 TI - Epichloe canadensis, a new interspecific epichloid hybrid symbiotic with Canada wildrye (Elymus canadensis). AB - Many Epichloe endophytes found in cool-season grasses are interspecific hybrids possessing much or all of the genomes of two or three progenitors. Here we characterize Epichloe canadensis sp. nov., a hybrid species inhabiting the grass species Elymus canadensis native to North America. Three distinct morphotypes were identified that were separated into two groups by molecular phylogenetic analysis. Sequence analysis of the translation elongation factor 1-alpha (tefA) and beta-tubulin (tubB) genes revealed two copies in all isolates examined. Phylogenetic analyses indicated that allele 1 of each gene was derived from Epichloe amarillans and allele 2 from Epichloe elymi. This is the first documentation of an interspecific hybrid endophyte derived from parents of strictly North American origins. Alkaloid gene profiling using primers specific to genes in the peramine, loline, indole-diterpene and ergot alkaloid pathways may indicate chemotypic variation in the ergot alkaloid and loline pathways between the assigned morphotypes. All isolates have the gene enabling the production of peramine but lack genes in the indole-diterpene biosynthesis pathway. Morphology and phylogenetic evidence support the designation of isolates from El. canadensis as a new interspecific hybrid species. PMID- 22675051 TI - Molecular evidence for Neotyphodium fungal endophyte variation and specificity within host grass species. AB - Host specificity of Neotyphodium species symbiotic with three grass species, Festuca arundinacea, Festuca pratensis and Lolium perenne, was studied based on comparisons of amplified fragment length polymorphisms (AFLP) between hosts and their corresponding endophytes. Endophytic fungi were isolated from 24 accessions of host plants. Neotyphodium identity was determined based on morphological characteristics observed in cultures and polymerase chain reaction analysis using specific primers. The results of AFLP data analysis revealed high genetic variation in plant and fungal endophyte species. Plant AFLP genotypes from different species clustered in three distinctive groups, congruent with species. A cluster analysis of AFLP data grouped endophytic isolates according to their host species and secondarily according to their host geographic distribution. The result of the AMOVA on AFLP data accounted for a large and significant proportion of genetic variation due to differences among plant and endophyte species. Phylogenetic groups of isolates corresponded to their respective host genotypes based on maximum parsimony phylograms. Comparisons of the two phylograms illustrated a significant congruence between nodes and branches of host and endophyte clades. These results strongly suggest host specificity of Neotyphodium fungal endophytes with their geographically distant host grasses within each species. PMID- 22675050 TI - A new Cortinarius of section Calochroi (Basidiomycota, Agaricomycetes) from Mediterranean Quercus woodlands (Italy). AB - A new species of Cortinarius, C. flavoaurantians sp. nov., is described from Italian Quercus woods based on both morphological and ITS rDNA data. This taxon is characterized by a yellowish pileus and cortina, a white universal veil and a pileipellis that reacts yellow-orange with KOH. Illustrations of the key micromorphological features and fresh basidiomata in situ are provided. Closely related species are discussed. PMID- 22675052 TI - Ectomycorrhizal association of three Lactarius species with Carpinus and Quercus trees in a Mexican montane cloud forest. AB - Ectomycorrhizal (EM) fungi are being monitored in the Santuario del Bosque de Niebla in the central region of Veracruz (eastern Mexico). Based on the comparison of DNA sequences (ITS rDNA) of spatiotemporally co-occurring basidiomes and EM root tips, we discovered the EM symbiosis of Lactarius indigo, L. areolatus and L. strigosipes with Carpinus caroliniana, Quercus xalapensis and Quercus spp. The host of the EM tips was identified by comparison of the large subunit of the ribulose-bisphosphate carboxylase gene (rbcL). Descriptions coupled with photographs of ectomycorrhizas and basidiomes are presented. PMID- 22675053 TI - Cirrosporium novae-zelandiae, an enigmatic coelomycete with meristem arthroconidia, with ancestors in the Eurotiomycetes. AB - A culture of Cirrosporium novae-zelandiae, the type species of a distinctive, monotypic coelomycete genus, was isolated from a specimen collected near the holotype locality in New Zealand. Light microscopic and environmental scanning electron microscopic observations confirm the details of the unusual meristem arthric conidium ontogeny presented in the protolog. For phylogenetic analysis, a dataset of 122 species representing nine classes of euascomycetes was assembled including sequences from nuclear small and large subunits (nc18S, nc28S) and mitochondrial small subunit (mr16S) ribosomal RNA and the largest and second largest subunits of RNA polymerase II (RPB1, RPB2). A five-gene phylogeny suggests that the fungus is phylogenetically related to the Eurotiomycetes. It sits alone on a long branch as a sister to the Mycocaliciales of the Mycocaliciomycetidae. Cirrosporium exhibits several morphological characters similar to those of members of the Mycocaliciales; however, the paucity of known anamorphs in this order does not offer any further clarification on possible relationships. It is clear that the rare and broadly distributed meristem arthric ontogenetic pattern is polyphyletic, occurring in widely separate groups of anamorphs of both the Ascomycota and Basidiomycota. PMID- 22675054 TI - A rare case of congenital epidermoid cyst of the hard palate. AB - Epidermoid cysts are benign conditions that are thought to derive from abnormally situated ectodermal inclusions in the oral cavity. They are generally found in hands, fingers, feet, ovaries and testicles but in oral cavity they represent a very rare event. This is the first case of an intraosseous epidermoid cyst situated in the hard palate. Healing was uneventful and there was no sign of recurrence in 2-years follow-up. PMID- 22675055 TI - Spontaneous pneumomediastinum following normal labour. AB - A young, previously well primigravida presented a few hours after a short labour with sudden onset chest pain, shortness of breath and odynophagia. She had subcutaneous emphysema but did not have significant cardiorespiratory compromise. She was found to have a spontaneous pneumomediastinum, likely secondary to raised intrathoracic pressure during labour. Similar cases have been reported previously, however there are often risk factors associated such as pre-existing lung disease and illicit drug use for which this patient did not have a significant history. The patient made a speedy recovery without requiring invasive management, as is the case for most patients documented in the literature. Consideration should be given to subsequent labours for this patient to minimise excessive intrathoracic pressure, however recurrence is rarely documented. This case is useful for healthcare professionals in assessing patients with chest pain as a reminder that unusual presentations can be diagnosed through thorough history and examination. PMID- 22675056 TI - Not all infantile respiratory distress in winter is bronchiolitis: congenital lobar emphysema. AB - The authors report the case of a 4-week-old male infant presented during the winter period with respiratory distress. He had a 3 day history of cough and coryza, and a 2 day history of breathlessness and reduced feeding. He had evidence of tachypnoea, subcostal recession and hypoxia on examination. An initial diagnosis of bronchiolitis was made. The authors explore how the correct diagnosis of congenital lobar emphysema (CLE) was reached, highlighting key clinical signs and investigations. He had evidence of a hyperinflated right middle lobe, with collapse of right upper and lower lobes and left upper lobe with associated mediastinal shift on chest x-ray (CXR) and CT scan. He was referred to the regional Paediatric Cardiothoracic Centre where right middle lobectomy was performed with complete resolution of his respiratory distress and re-expansion of the compressed lobes on CXR. Current literature concerning CLE is reviewed. PMID- 22675057 TI - Septic shock due to Fournier's gangrene of the scrotum. AB - A 57-year-old morbidly obese (160 kg) man presented with a 12 h history of severe bilateral scrotal pain and swelling. His scrotum was erythematous, with cellulitis advancing superiorly along the anterior abdominal wall. He was in septic shock. Following resuscitation with intravenous fluids, commencement of vasopressor infusion and broad-spectrum antimicrobials, he underwent surgical exploration and debridement. This revealed a devitalised gangrenous scrotum with abscess formation noted in the ischio-rectal spaces. This was debrided posteriorly to the wall of the rectum. The penis was de-gloved. Both testicles were spared. A colostomy was performed on day 3 to maintain a clean environment for healing. Subsequent scrotal reconstruction and grafting was performed with a pedicled gracilis flap and split skin grafting. The colostomy was reversed at 5 months. PMID- 22675058 TI - A rare presentation of spinal epidural abscess. AB - A 77-year-old retired engineer presented to accident and emergency with deteriorating shortness of breath that had been troubling him for several months. At that time, he was being investigated by a chest physician who had identified bilateral diaphragmatic paralysis on ultrasound and was awaiting further imaging. Clinical assessment and nerve conduction studies on this admission were compatible with a diagnosis of motor neuron disease but specialist neurology input recommended an MRI to rule out cord pathology. This proved problematic as the patient was non-invasive ventilation dependent and unable to lay supine as this further compromised his respiratory function. To ensure that a potentially reversible cause for his symptoms was identified, the patient was intubated for an MRI which subsequently demonstrated multi level spinal epidural empyema. The benefits of neurosurgical intervention were judged to be uncertain at best, and following discussion with the family, active care was withdrawn. The patient passed away shortly thereafter. PMID- 22675059 TI - Non-syndromic supernumerary premolars. PMID- 22675060 TI - Lhermitte-Duclos and Cowden diseases: breast cancer as an unusual initial presentation of these overlapping conditions. AB - The authors report the case of a woman presenting with breast cancer who subsequently developed neck pain and ataxia. She had a family history of breast cancer and Cowden disease. A MRI study of the brain revealed a lesion in the cerebellum consistent with Lhermitte-Duclos disease (LDD) and a lesion consistent with a meningioma in the temporal lobe. This case emphasises the importance of awareness of the overlap between LDD and Cowden disease. PMID- 22675062 TI - Osteoporosis in men: an Endocrine Society clinical practice guideline. AB - OBJECTIVE: The aim was to formulate practice guidelines for management of osteoporosis in men. EVIDENCE: We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe the strength of recommendations and evidence quality. CONSENSUS PROCESS: Consensus was guided by systematic evidence reviews, one in-person meeting, and multiple conference calls and e-mails. Task Force drafts were reviewed successively by The Endocrine Society's Clinical Guidelines Subcommittee and Clinical Affairs Core Committee; representatives of ASBMR, ECTS, ESE, ISCD; and members at large. At each stage, the Task Force received written comments and incorporated needed changes. The reviewed document was approved by The Endocrine Society Council before submission for peer review. CONCLUSIONS: Osteoporosis in men causes significant morbidity and mortality. We recommend testing higher risk men [aged >=70 and men aged 50-69 who have risk factors (e.g. low body weight, prior fracture as an adult, smoking, etc.)] using central dual-energy x-ray absorptiometry. Laboratory testing should be done to detect contributing causes. Adequate calcium and vitamin D and weight bearing exercise should be encouraged; smoking and excessive alcohol should be avoided. Pharmacological treatment is recommended for men aged 50 or older who have had spine or hip fractures, those with T-scores of -2.5 or below, and men at high risk of fracture based on low bone mineral density and/or clinical risk factors. Treatment should be monitored with serial dual-energy x-ray absorptiometry testing. PMID- 22675063 TI - Caveat emptor: does testosterone treatment reduce mortality in men? PMID- 22675070 TI - Patient guide to osteoporosis in men. PMID- 22675071 TI - Paratome: an online tool for systematic identification of antigen-binding regions in antibodies based on sequence or structure. AB - Antibodies are capable of specifically recognizing and binding antigens. Identification of the antigen-binding site, commonly dubbed paratope, is of high importance both for medical and biological applications. To date, the identification of antigen-binding regions (ABRs) relies on tools for the identification of complementarity-determining regions (CDRs). However, we have shown that up to 22% of the residues that actually bind the antigen fall outside the traditionally defined CDRs. The Paratome web server predicts the ABRs of an antibody, given its amino acid sequence or 3D structure. It is based on a set of consensus regions derived from a structural alignment of a non-redundant set of all known antibody-antigen complexes. Given a query sequence or structure, the server identifies the regions in the query antibody that correspond to the consensus ABRs. An independent set of antibody-antigen complexes was used to test the server and it was shown to correctly identify at least 94% of the antigen binding residues. The Paratome web server is freely available at http://www.ofranlab.org/paratome/. PMID- 22675072 TI - Contrasting enantioselective DNA preference: chiral helical macrocyclic lanthanide complex binding to DNA. AB - There is great interest in design and synthesis of small molecules which selectively target specific genes to inhibit biological functions in which particular DNA structures participate. Among these studies, chiral recognition has been received much attention because more evidences have shown that conversions of the chirality and diverse conformations of DNA are involved in a series of important life events. Here, we report that a pair of chiral helical macrocyclic lanthanide (III) complexes, (M)-Yb[L(SSSSSS)](3+) and (P) Yb[L(RRRRRR)](3+), can enantioselectively bind to B-form DNA and show remarkably contrasting effects on GC-rich and AT-rich DNA. Neither of them can influence non B-form DNA, nor quadruplex DNA stability. Our results clearly show that P enantiomer stabilizes both poly(dG-dC)(2) and poly(dA-dT)(2) while M-enantiomer stabilizes poly(dA-dT)(2), however, destabilizes poly(dG-dC)(2). To our knowledge, this is the best example of chiral metal compounds with such contrasting preference on GC- and AT-DNA. Ligand selectively stabilizing or destabilizing DNA can interfere with protein-DNA interactions and potentially affect many crucial biological processes, such as DNA replication, transcription and repair. As such, bearing these unique capabilities, the chiral compounds reported here may shed light on the design of novel enantiomers targeting specific DNA with both sequence and conformation preference. PMID- 22675073 TI - KOMODO: a web tool for detecting and visualizing biased distribution of groups of homologous genes in monophyletic taxa. AB - The enrichment analysis is a standard procedure to interpret 'omics' experiments that generate large gene lists as outputs, such as transcriptomics and protemics. However, despite the huge success of enrichment analysis in these classes of experiments, there is a surprising lack of application of this methodology to survey other categories of large-scale biological data available. Here, we report Kegg Orthology enrichMent-Online DetectiOn (KOMODO), a web tool to systematically investigate groups of monophyletic genomes in order to detect significantly enriched groups of homologous genes in one taxon when compared with another. The results are displayed in their proper biochemical roles in a visual, explorative way, allowing users to easily formulate and investigate biological hypotheses regarding the taxonomical distribution of genomic elements. We validated KOMODO by analyzing portions of central carbon metabolism in two taxa extensively studied regarding their carbon metabolism profile (Enterobacteriaceae family and Lactobacillales order). Most enzymatic activities significantly biased were related to known key metabolic traits in these taxa, such as the distinct fates of pyruvate (the known tendency of lactate production in Lactobacillales and its complete oxidation in Enterobacteriaceae), demonstrating that KOMODO could detect biologically meaningful differences in the frequencies of shared genomic elements among taxa. KOMODO is freely available at http://komodotool.org. PMID- 22675075 TI - T-REX: a web server for inferring, validating and visualizing phylogenetic trees and networks. AB - T-REX (Tree and reticulogram REConstruction) is a web server dedicated to the reconstruction of phylogenetic trees, reticulation networks and to the inference of horizontal gene transfer (HGT) events. T-REX includes several popular bioinformatics applications such as MUSCLE, MAFFT, Neighbor Joining, NINJA, BioNJ, PhyML, RAxML, random phylogenetic tree generator and some well-known sequence-to-distance transformation models. It also comprises fast and effective methods for inferring phylogenetic trees from complete and incomplete distance matrices as well as for reconstructing reticulograms and HGT networks, including the detection and validation of complete and partial gene transfers, inference of consensus HGT scenarios and interactive HGT identification, developed by the authors. The included methods allows for validating and visualizing phylogenetic trees and networks which can be built from distance or sequence data. The web server is available at: www.trex.uqam.ca. PMID- 22675074 TI - Integration of Hi-C and ChIP-seq data reveals distinct types of chromatin linkages. AB - We have analyzed publicly available K562 Hi-C data, which enable genome-wide unbiased capturing of chromatin interactions, using a Mixture Poisson Regression Model and a power-law decay background to define a highly specific set of interacting genomic regions. We integrated multiple ENCODE Consortium resources with the Hi-C data, using DNase-seq data and ChIP-seq data for 45 transcription factors and 9 histone modifications. We classified 12 different sets (clusters) of interacting loci that can be distinguished by their chromatin modifications and which can be categorized into two types of chromatin linkages. The different clusters of loci display very different relationships with transcription factor binding sites. As expected, many of the transcription factors show binding patterns specific to clusters composed of interacting loci that encompass promoters or enhancers. However, cluster 9, which is distinguished by marks of open chromatin but not by active enhancer or promoter marks, was not bound by most transcription factors but was highly enriched for three transcription factors (GATA1, GATA2 and c-Jun) and three chromatin modifiers (BRG1, INI1 and SIRT6). To investigate the impact of chromatin organization on gene regulation, we performed ribonucleicacid-seq analyses before and after knockdown of GATA1 or GATA2. We found that knockdown of the GATA factors not only alters the expression of genes having a nearby bound GATA but also affects expression of genes in interacting loci. Our work, in combination with previous studies linking regulation by GATA factors with c-Jun and BRG1, provides genome-wide evidence that Hi-C data identify sets of biologically relevant interacting loci. PMID- 22675076 TI - Re-splicing of mature mRNA in cancer cells promotes activation of distant weak alternative splice sites. AB - Transcripts of the human tumor susceptibility gene 101 (TSG101) are aberrantly spliced in many cancers. A major aberrant splicing event on the TSG101 pre-mRNA involves joining of distant alternative 5' and 3' splice sites within exon 2 and exon 9, respectively, resulting in the extensive elimination of the mRNA. The estimated strengths of the alternative splice sites are much lower than those of authentic splice sites. We observed that the equivalent aberrant mRNA could be generated from an intron-less TSG101 gene expressed ectopically in breast cancer cells. Remarkably, we identified a pathway-specific endogenous lariat RNA consisting solely of exonic sequences, predicted to be generated by a re-splicing between exon 2 and exon 9 on the spliced mRNA. Our results provide evidence for a two-step splicing pathway in which the initial constitutive splicing removes all 14 authentic splice sites, thereby bringing the weak alternative splice sites into close proximity. We also demonstrate that aberrant multiple-exon skipping of the fragile histidine triad (FHIT) pre-mRNA in cancer cells occurs via re splicing of spliced FHIT mRNA. The re-splicing of mature mRNA can potentially generate mutation-independent diversity in cancer transcriptomes. Conversely, a mechanism may exist in normal cells to prevent potentially deleterious mRNA re splicing events. PMID- 22675077 TI - Exome sequencing identifies a novel TRPV4 mutation in a CMT2C family. PMID- 22675078 TI - Genomic medicine enters the neurology clinic. PMID- 22675079 TI - Does experience doing lumbar punctures result in expertise? A medical maxim bites the dust. PMID- 22675080 TI - Simulation-based education with mastery learning improves residents' lumbar puncture skills. AB - OBJECTIVE: To evaluate the effect of simulation-based mastery learning (SBML) on internal medicine residents' lumbar puncture (LP) skills, assess neurology residents' acquired LP skills from traditional clinical education, and compare the results of SBML to traditional clinical education. METHODS: This study was a pretest-posttest design with a comparison group. Fifty-eight postgraduate year (PGY) 1 internal medicine residents received an SBML intervention in LP. Residents completed a baseline skill assessment (pretest) using a 21-item LP checklist. After a 3-hour session featuring deliberate practice and feedback, residents completed a posttest and were expected to meet or exceed a minimum passing score (MPS) set by an expert panel. Simulator-trained residents' pretest and posttest scores were compared to assess the impact of the intervention. Thirty-six PGY2, 3, and 4 neurology residents from 3 medical centers completed the same simulated LP assessment without SBML. SBML posttest scores were compared to neurology residents' baseline scores. RESULTS: PGY1 internal medicine residents improved from a mean of 46.3% to 95.7% after SBML (p < 0.001) and all met the MPS at final posttest. The performance of traditionally trained neurology residents was significantly lower than simulator-trained residents (mean 65.4%, p < 0.001) and only 6% met the MPS. CONCLUSIONS: Residents who completed SBML showed significant improvement in LP procedural skills. Few neurology residents were competent to perform a simulated LP despite clinical experience with the procedure. PMID- 22675082 TI - Exome sequencing as a diagnostic tool in a case of undiagnosed juvenile-onset GM1 gangliosidosis. AB - OBJECTIVE: To utilize high-throughput sequencing to determine the etiology of juvenile-onset neurodegeneration in a 19-year-old woman with progressive motor and cognitive decline. METHODS: Exome sequencing identified an initial list of 133,555 variants in the proband's family, which were filtered using segregation analysis, presence in dbSNP, and an empirically derived gene exclusion list. The filtered list comprised 52 genes: 21 homozygous variants and 31 compound heterozygous variants. These variants were subsequently scrutinized with predicted pathogenicity programs and for association with appropriate clinical syndromes. RESULTS: Exome sequencing data identified 2 GLB1 variants (c.602G>A, p.R201H; c.785G>T, p.G262V). beta-Galactosidase enzyme analysis prior to our evaluation was reported as normal; however, subsequent testing was consistent with juvenile-onset GM1-gangliosidosis. Urine oligosaccharide analysis was positive for multiple oligosaccharides with terminal galactose residues. CONCLUSIONS: We describe a patient with juvenile-onset neurodegeneration that had eluded diagnosis for over a decade. GM1-gangliosidosis had previously been excluded from consideration, but was subsequently identified as the correct diagnosis using exome sequencing. Exome sequencing can evaluate genes not previously associated with neurodegeneration, as well as most known neurodegeneration-associated genes. Our results demonstrate the utility of "agnostic" exome sequencing to evaluate patients with undiagnosed disorders, without prejudice from prior testing results. PMID- 22675081 TI - Exome sequencing in an SCA14 family demonstrates its utility in diagnosing heterogeneous diseases. AB - OBJECTIVE: Genetic heterogeneity is common in many neurologic disorders. This is particularly true for the hereditary ataxias where at least 36 disease genes or loci have been described for spinocerebellar ataxia and over 100 genes for neurologic disorders that present primarily with ataxia. Traditional genetic testing of a large number of candidate genes delays diagnosis and is expensive. In contrast, recently developed genomic techniques, such as exome sequencing that targets only the coding portion of the genome, offer an alternative strategy to rapidly sequence all genes in a comprehensive manner. Here we describe the use of exome sequencing to investigate a large, 5-generational British kindred with an autosomal dominant, progressive cerebellar ataxia in which conventional genetic testing had not revealed a causal etiology. METHODS: Twenty family members were seen and examined; 2 affected individuals were clinically investigated in detail without a genetic or acquired cause being identified. Exome sequencing was performed in one patient where coverage was comprehensive across the known ataxia genes, excluding the known repeat loci which should be examined using conventional analysis. RESULTS: A novel p.Arg26Gly change in the PRKCG gene, mutated in SCA14, was identified. This variant was confirmed using Sanger sequencing and showed segregation with disease in the entire family. CONCLUSIONS: This work demonstrates the utility of exome sequencing to rapidly screen heterogeneous genetic disorders such as the ataxias. Exome sequencing is more comprehensive, faster, and significantly cheaper than conventional Sanger sequencing, and thus represents a superior diagnostic screening tool in clinical practice. PMID- 22675084 TI - Bloody nipple discharge in a 7-month-old boy. AB - Isolated bloody nipple discharge is rare in infancy and is usually idiopathic. Discharge commonly resolves spontaneously, and ultrasonography is a useful diagnostic technique to detect the cause of discharge. The authors report a 7 month-old boy who presented with unilateral spontaneous bloody nipple discharge for 1 month without signs of infection or mass. PMID- 22675083 TI - Individual maize chromosomes in the C(3) plant oat can increase bundle sheath cell size and vein density. AB - C(4) photosynthesis has evolved in at least 66 lineages within the angiosperms and involves alterations to the biochemistry, cell biology, and development of leaves. The characteristic "Kranz" anatomy of most C(4) leaves was discovered in the 1890s, but the genetic basis of these traits remains poorly defined. Oat * maize addition lines allow the effects of individual maize (Zea mays; C(4)) chromosomes to be investigated in an oat (Avena sativa; C(3)) genetic background. Here, we have determined the extent to which maize chromosomes can introduce C(4) characteristics into oat and have associated any C(4)-like changes with specific maize chromosomes. While there is no indication of a simultaneous change to C(4) biochemistry, leaf anatomy, and ultrastructure in any of the oat * maize addition lines, the C(3) oat leaf can be modified at multiple levels. Maize genes encoding phosphoenolpyruvate carboxylase, pyruvate, orthophosphate dikinase, and the 2' oxoglutarate/malate transporter are expressed in oat and generate transcripts of the correct size. Three maize chromosomes independently cause increases in vein density, and maize chromosome 3 results in larger bundle sheath cells with increased cell wall lipid deposition in oat leaves. These data provide proof of principle that aspects of C(4) biology could be integrated into leaves of C(3) crops. PMID- 22675085 TI - Breast milk: friend or foe? AB - Anaphylaxis can occur secondary to breastfeeding. The authors present a case of a 30-year-old woman who complained of chest tightness, shortness of breath and a rash on the third day postpartum. She was treated for anaphylaxis and her symptoms resolved. Because she had taken tramadol prior to this event, a drug reaction was initially suspected. However, she experienced further episodes related to breastfeeding, despite stopping tramadol. Effective control of her symptoms was achieved with regular antihistamines, enabling her to continue breastfeeding. Antihistamines were interrupted after 8 weeks at which point lactation (in hospital) was once again associated with anaphylaxis. The diagnosis of breastfeeding induced anaphylaxis was made. There are six previously reported cases of breastfeeding induced anaphylaxis. The authors describe the second case of breastfeeding anaphylaxis extending beyond the neonatal period, controlled with antihistamines. PMID- 22675086 TI - Primary torsion of vermiform appendix mimicking acute appendicitis. AB - Acute appendicitis is a common condition, 8% of the developed world have an appendicectomy in their lifetime. However, torsion of the appendix is a rare disorder first described in 1918 presenting in a manner undistinguishable from acute appendicitis. The authors describe a case of a 48-year-old man who presented with a short history consistent with acute appendicitis. At open appendicectomy, was found to have an acute clockwise torsion of the vermiform appendix at a point 0.5 cm from its base. Histological examination of the specimen was consistent with torsion of the appendix but no underlying cause for the torsion was identified. The postoperative recovery was uneventful; the patient received intravenous antibiotics for a further 48 h and was discharged home without any complications. PMID- 22675087 TI - Atypical presentation of purpura fulminans following sepsis in an adult. AB - A 67-year-old morbidly obese female with a background of stage 4 chronic renal failure, ischaemic heart disease, congestive cardiac failure, atrial fibrillation and type 2 diabetes mellitus presented with sepsis and necrotic lesions of the proximal lower limbs. Initial histological findings were consistent with the clinical diagnosis of calciphylaxis and supportive treatment was commenced with addition of a phosphate binder and dietary restriction. Due to high anaesthetic risk, her wounds were managed with larva therapy in the first instance, however, ultimately surgical debridement was the required. Repeat histology from a further biopsy revealed necrosis secondary to numerous thrombi in the cutaneous vessels and a new diagnosis of purpura fulminans was made, likely secondary to her sepsis. Unfortunately, despite aggressive medical and surgical treatment measures, this patient died of multiple organ dysfunction following a prolonged admission. PMID- 22675088 TI - Enlarged extrahepatic portal vein aneurysm in a non-cirrhotic patient: a therapeutic dilemma. AB - The authors report a case of a 75-year-old woman who was seen about 5 years ago and found to have asymptomatic gallstone and extrahepatic portal vein aneurysm (PVA) adjacent to the gallbladder. Further investigations revealed no evidence of cirrhosis. A follow-up ultrasound revealed that the PVA increased in diameter from 20 to 25 mm over 5 years and surgical intervention was recommended. Cholecystectomy and omental wrapping around PVA were performed. Postoperative follow-up investigations for 3 years revealed no increases in PVA diameter. Although PVA is clinically rare, the authors believe that their case report presents an overview of related literature, discusses indications for surgery in PVA and describes their surgical method for managing PVA. PMID- 22675089 TI - Hydroxychloroquine as a glucose lowering drug. AB - The authors report a remarkable glucose lowering side effect of the often used drug hydroxychloroquine (Plaquenil) in an otherwise healthy non-diabetic patient, who presented with severe hypoglycaemia. Although the mechanism has not been clarified yet, increased insulin sensitivity as well as decreased insulin degradation is suggested to contribute to the reduction in serum glucose levels. Clinicians prescribing this drug must be warranted and check glucose levels in the initial phase. Moreover, hydroxychloroquine might be applied as therapeutic in refractory diabetic rheumatics or rheumatic patients at risk to develop diabetes mellitus. PMID- 22675090 TI - Juniper tar (cade oil) poisoning in new born after a cutaneous application. AB - Juniper tar (cade oil) is distilled from the branches and wood of Juniperus oxycedrus. It contains etheric oils, triterpene and phenols, used for many purposes in folk medicine. The authors report a case of a previously healthy new born treated with a topical application of Juniperus oxycedrus for atopic dermatosis The poisoning caused convulsions, collapsus, acute pulmonary oedema, renal failure and hepatotoxicity. The newborn survived after supportive and symptomatic treatment, and discharged in a good condition on the eleventh day of hospitalisation in intensive care unit. PMID- 22675091 TI - Psittacosis infection and tracheobronchomalacia in a patient undergoing thyroidectomy. AB - A 34-year-old woman with papillary thyroid carcinoma underwent total thyroidectomy with central and lateral lymphadenectomy. Immediate airway compromise required re-intubation immediately after surgery. Marked tracheal and bronchial collapse of greater than 50% of the lumen indicated tracheobronchomalacia. Subsequent attempts at extubation failed over the next week. The patient soon developed evidence of a lower respiratory tract infection. Empirical treatment with penicillins was unsuccessful. A clinical suspicion of chlamydia infection prompted initiation of macrolide treatment followed by resolution of both the patient's respiratory infection and tracheobronchomalacia. Serology returned positive for Chlamydophila psittaci infection. It later transpired that the patient had symptoms of an upper respiratory tract infection just prior to surgery. This case demonstrates an interesting and unreported cause of tracheobronchomalacia as well as providing a good lesson on the importance of preoperative screening for infection. PMID- 22675092 TI - Skin rash and pneumonia in a young male. PMID- 22675093 TI - Pseudo triggering finger caused by a giant cell tumour of the extensor aspect of the right index finger. AB - Peudo-triggering of a finger due to a giant cell tumour of the dorsal aspect of a finger has not been reported in the literature. Hence the authors wish to report this unique case of interest. PMID- 22675094 TI - A rare cause of abdominal angina. AB - The authors report a case of a young male with median arcuate ligament syndrome (MALS). An abnormally low insertion of the median arcuate ligament fibres caused extrinsic compression and stenosis of the coeliac trunk. However, partial dissection of ligament fibres by laparoscopic surgery did not relieve abdominal angina. Multidetector CT confirmed that MALS did not differ from the preoperative scan. The arcuate ligament compressed the coeliac trunk on expiration, thereby eliciting occlusion of the coeliac trunk. Inspiration induced decompression of the ligament with partial release of occlusion of the coeliac trunk. This leads to hypo-perfusion of intestinal organs and abdominal angina. Considering the severe impairment of quality of life, open surgery for decompression of the coeliac trunk with vascular reconstruction is a reasonable option. PMID- 22675095 TI - Rupture of bicornuate uterus. AB - A primigravida aged 20 years was referred to Vydehi Institute of Medical Sciences with diagnosis of 30 weeks of period of gestation with eclampsia and failure to respond to induction with misoprostol and she was on Pritchard regimen for the treatment of eclampsia and there was no response to induction of labour and emergency ultrasound was taken and it showed an extrauterine gestation of 30 weeks gestation with fetal demise and free fluid in peritoneum. A tentative diagnosis of secondary abdominal pregnancy with eclampsia was made and she was taken for emergency laprotomy. Intra operative findings showed haemoperitoneum, fetus with placenta and membranes in the peritoneal cavity, there was bicornuate uterus and right horn was ruptured from the fundus to about 8 cm down in the posterior aspect and ruptured part was sutured in two layers. After securing perfect haemostasis, abdomen was closed. This paper illustrates a case report of uterine anomaly with 30 weeks period of gestation and eclampsia and rupture following induction with prostaglandins. PMID- 22675096 TI - Overwhelming primary Epstein-Barr virus infection requiring corticosteroid treatment. AB - A 20-year-old woman presented with a 2-week history of fever and malaise. Physical examination was unremarkable. Viral infection was suspected and Epstein Barr virus serology confirmed acute infectious mononucleosis. During admission, she gradually developed pancytopenia and liver enzyme abnormalities. The patient clinically deteriorated with persisting fever, orthostatic hypotension and hepatosplenomegaly. Bone marrow examination showed haemophagocytic lymphohistiocytosis (HLH). Treatment with high-dose corticosteroids was started and patient recovered quickly. Ferritin decreased immediately, fever resolved within 3 days, viral clearance was reached within 3 weeks. Steroid therapy was gradually tapered off in three months. The Histiocyte Society recommends immunochemotherapy with steroids, etoposide and cyclosporine. Potential side effects of etoposide are severe bone marrow depression and leukaemia. Our patient survived on corticosteroids alone. Early recognition of HLH and prompt treatment are of utmost importance for survival. Treatment with steroids alone can be life saving. PMID- 22675097 TI - Tubercular serpiginous-like choroiditis. AB - Choroidal tuberculosis (TB) infection may present itself as a diffuse choroiditis that resembles serpiginous choroiditis, usually treated with immunossupressants. Recent studies have demonstrated that patients with serpiginous-like choroiditis and evidence of systemic or latent TB are best treated with antituberculosis treatment (ATT) in addition to the corticosteroid therapy. The authors present a case of a 58-year-old man with decreased vision in his left eye. His best corrected visual acuity was 20/20 right eye and 20/200 left eye. Funduscopic examination revealed a diffuse choroiditis. Mantoux skin test showed an area of induration measuring 30*35 mm and the patient started ATT with complete resolution of retinal lesions after 2 weeks of treatment. His final visual acuity was 20/25 in the left eye with no recurrences over a follow-up of 6 months. The use of ATT in these patients is likely to reduce active inflammation and eliminate future recurrences. PMID- 22675098 TI - Dermatomyositis masquerading musculoskeletal tuberculosis. AB - Dermatomyositis is a rare rheumatic disease which predominantly affects the muscles and skin requiring a protracted course of immunosuppressants which may predispose the patients to opportunistic infections. A 49-year-old lady was diagnosed to have dermatomyositis in August 2010 based on history, significantly raised creatine kinase level and muscle biopsy findings. She had recurrent admissions due to fever, myalgia and muscle weakness. She had spiking temperature despite high dose steroids, broad-spectrum antibiotics and antifungal agents. This prompted extensive investigation which leads us to the additional diagnosis of disseminated tuberculosis involving the lungs, muscles and bones. This case demonstrates the challenge in controlling the disease activity of dermatomyositis with immunosuppressants in the setting of disseminated tuberculosis. PMID- 22675099 TI - Do not forget about HELLP! AB - A 32-year-old female para 4 gravi 3, who was 21 weeks pregnant, presented to the emergency department (ED) with a 2-day history of abdominal pain, headache, blurred vision and vomiting. On arrival, she was agitated and confused with a blood pressure 162/106 mm Hg, pulse rate 107, respiratory rate 18, temperature 37 degrees Celsius, point of care blood glucose 6.2 and her Glasgow coma scale was 13/15 M6V4E3. Paramedics witnessed seizure-like activity lasting <1 min during transport. A diagnosis of eclampsia complicated by the HELLP syndrome (haemolysis, elevated liver enzymes, low platelets count) was made. She was commenced on magnesium and labetalol intravenously for blood pressure control. Initial blood test results were consistent with the HELLP syndrome. Recognition of the HELLP syndrome with prompt management of blood pressure and clotting abnormalities is essential in the ED setting. An aggressive multidisciplinary approach is a key to optimise the prognosis for mother and fetus. PMID- 22675100 TI - Idiopathic retroperitoneal fibrosis presenting with recurrent bilateral uveitis. AB - Patients with recurrent uveitis are often evaluated for the presence of underlying systemic disease. The authors describe a 55-year-old black female who presented with isolated recurrent anterior uveitis. Laboratory evaluations were notable for elevated inflammatory markers. She subsequently developed left lower extremity painless swelling; ultrasound evaluation was negative for deep venous thrombosis. CT scan of her abdomen and pelvis demonstrated multiple amorphous soft tissue densities throughout the small bowel mesentery and retroperitoneum, associated with left-sided hydronephrosis. Histopathology of a retroperitoneal mass demonstrated retroperitoneal fibrosis (RPF). Treatment with systemic corticosteroids led to shrinkage of her mesenteric and retroperitoneal masses, resolution of uveitis and normalisation of inflammatory markers. Albeit rare, RPF should be considered in the diagnostic investigation of patients with recurrent uveitis, especially those with abdominopelvic or lower extremity complaints. PMID- 22675101 TI - Cerebral infarction due to smoker's polycythemia. AB - A 65-year-old man presented with fluctuating focal neurological deficits and neuroimaging findings of multiple small cerebral infarctions. His medical investigation revealed a >100 pack/year smoking history, and a haematocrit >60. Subsequent investigations led to a diagnosis of cerebral infarction due to smoker's polycythemia, the third such case reported in the medical literature. The patient's neurological deficits resolved completely with subsequent haematocrit reduction. This brief report reviews the differential diagnosis of polycythemia, current knowledge of the mechanisms by which smoker's polycythemia may lead to ischemic stroke, and recommendations for management. PMID- 22675102 TI - Mysterious but not serious? PMID- 22675103 TI - Happy Puppet syndrome. AB - Happy Puppet syndrome is characterised by a partial deficit of paired autosomal chromosome 15. It is a neuro-genetic disorder characterised by intellectual and developmental delay, sleep disturbance, seizures, jerky movements (especially hand-flapping), frequent laughter or smiling and usually a happy demeanour. It is also called as Angelman syndrome (AS). People with AS are sometimes known as 'angels', both because of the syndrome's name and because of their youthful, happy appearance. A 6.5-year-old girl is presented and clinical suspicion of AS was raised at the age of 4 years when she presented with mental retardation and epilepsy, absence of speech, inability to gait and unprovoked episodes of laughter. Fluorescent in situ hybridisation chromosomal analysis revealed micro deletion on the maternally derived allele of 15q chromosome. PMID- 22675104 TI - First-degree relatives with behavioural adverse effects on statins. AB - Irritability, aggression and other adverse behavioural effects have been associated with the use of statins (3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors) and other drug classes. A number of studies have also linked low cholesterol with aggression and violence. This paper presents the cases of two first-degree male relative patients (father and son) identified by self-referral to the University of California in San Diego Statin Effects Study. Both patients experienced behavioural adverse effects on statins including irritability and aggression, however neither patient recognised a significant change in their behaviour. This may be the first report of behavioural adverse effects manifested on statins by first-degree male relatives, which may suggest possible familial/biological predisposition. These cases also highlight the issue of externalisation by patients of the origin of interpersonal discord, which may serve as an obstacle to adverse effects reporting and lead to negative outcomes for patients, and for those around them. PMID- 22675105 TI - Pacemaker lead-straight through the heart. PMID- 22675106 TI - A novel nose piercing. PMID- 22675107 TI - Clinically significant interaction between warfarin and popular cough lozenges 'Fisherman's Friend'. AB - The authors report a highly probable and clinically relevant interaction between warfarin and the popular cough lozenges 'Fisherman's Friends' in a 67-year-old man, whereby ingestion of these lozenges for approximately 1 month was associated with a significant reduction in international normalised ratio to subtherapeutic levels. PMID- 22675108 TI - Obsessive compulsive disorder with psychosis NOS, in an asexual male: a diagnostic challenge. AB - A 28-year-old asexual Malaysian male presented for emergency assessment with suicidal thoughts, paranoid delusions and increasing time spent on ritualistic behaviours that included hand washing, door checking and religious chanting. His obsessions were primarily related to counting, perfectionism, contamination and chanting. The patient found himself compelled to complete numerous rituals including chanting religiously to 1000, having to restart in the event of an error during such and also described delusions of being followed by a woman who was analysing his life pattern in order to steal from him. He then started to proclaim himself to be Buddha as he believed this would keep his dead grandmother away from him, thus avoiding supposed persecution from her. Following optimisation of both escitalpram and olanzapine, a slight reduction in the patient's ritualistic behaviour and psychotic phenomenon were witnessed. PMID- 22675109 TI - Arthropod larvae misidentified as parasitic worm infection. AB - A healthy, asymptomatic man living in London, presented with seeing 'worms' in his toilet for two successive summer seasons. Repeated microscopic examination and cultures of both his faeces and urine were normal. He was empirically treated with multiple courses of antihelminthics without resolution of this problem. A sample of the worms was obtained, and positively identified as arthropod larvae under microscopic examination. These larvae do not parasitically colonise humans. It was subsequently deduced that a flying arthropod (most likely Culex pipiens mosquito) had laid eggs in standing toilet water, and the hatched larvae had been mistaken for parasitic worms. The patient was declared free of parasites and remains healthy. This case illustrates the dangers of starting empirical treatment without positive confirmation of causative organisms, which can result in unnecessary and potentially harmful treatment. PMID- 22675110 TI - Rhabdomyolysis with acute kidney injury in a case of hanging. AB - Although well-known as a complication of other hypoxic conditions such as near drowning, status asthmaticus and carbon monoxide poisoning, rhabdomyolysis has not been reported in patients with hanging. The authors report a case of partial hanging complicated by rhabdomyolysis and acute kidney injury. PMID- 22675111 TI - Gluteo-vaginal fistula: a long-term complication of posterior intravaginal slingplasty. AB - A 67-year-old lady presented to the surgical outpatient clinic with a 4 month history of recurrent purulent discharge from her left buttock. Four years and 4 months prior to this she underwent a posterior intravaginal slingoplasty for vaginal prolapse and urinary stress incontinence. An MRI demonstrated a long gluteo-vaginal fistula tract from the posterior wall of the vaginal vault through the left ischiorectal fossa to the skin. An examination under anaesthesia revealed that the fistulous tract was surrounding the intact mesh used for the posterior intravaginal slingoplasty. The mesh was removed, the fistula tract excised and the perineal wound marsupialised. The patient was discharged 5 days later. The wound healed within 4 weeks and she remains sepsis free 2 years on. PMID- 22675112 TI - Opsoclonus-Myoclonus syndrome. PMID- 22675113 TI - Skin spread from an intracranial glioblastoma: case report and review of the literature. AB - Extracranial metastases secondary to intracranial neoplasm are extremely rare. The incidence of extraneural metastases of brain tumours is estimated to be less than 0.4%. The authors report a case of postoperative intracranial glioblastoma spreading to the skin in an adult patient. In this case, the radiological images and surgical findings suggest that the potential dissemination mechanism is as a result of infiltration through the surgical wound site. The primary tumour-upon coming into contact with the dura and the skin-mimicked the characteristics of both tissues. This case supports the theory of risk of spread through the durotomy site, although this phenomenon is extremely rare. Both the specific pathogenic mechanisms as well as the ideal and effective management have not been established yet and require further investigation. PMID- 22675115 TI - Do not forget decubitus view: a simple and useful tool in acute abdomen. PMID- 22675114 TI - Cyanide: an unreported cause of neurological complications following smoke inhalation. AB - Although the combustion of natural and synthetic products can yield cyanide, its toxic role in residential fires is unclear. This case concerns a woman aged over 50 years who presented comatose, pulseless and apnoeic after a domestic fire. Cardiopulmonary resuscitation and on-site administration of 2.5 g hydroxocobalamin as an antidote to cyanide resulted in a return of spontaneous circulation. On admission to the intensive care unit, the patient was treated with hyperbaric oxygen for suspected carbon monoxide poisoning. In a blood specimen collected at the scene before hydroxocobalamin administration, blood cyanide and carbon monoxide levels were 68 umol/l and 10.9%. On admission to hospital, plasma lactate was at 4.6 mmol/l. Brain scans revealed lesions which were confirmed 2 months later, consistent with the haemorrhagic necrosis often seen after poisoning by cyanide. These data suggest that smoke inhalation in a residential fire may cause cyanide poisoning. This case provides clinical, biological, analytical and brain imaging data supporting the hypothesis of the toxic role of smoke-induced cyanide poisoning which may result in neurological sequelae. PMID- 22675116 TI - Dynamic flexibility of the ATPase p97 is important for its interprotomer motion transmission. AB - The hexameric protein p97, a very abundant type II AAA ATPase (ATPase associated with various cellular activities), is involved in a diverse range of cellular functions. During its ATPase cycle p97 functions as an ATP motor, converting the chemical energy released upon hydrolysis of ATP to ADP into mechanical work, which is then directed toward the proteins that serve as substrates. A key question in this process is: How is the nucleotide-induced motion transmitted from the C-terminal ATPase domain (the D2 domain) of p97 to the distant N terminal substrate-processing domain? We have previously reported the surprising finding that motion transmission between the two ATPase domains (the D2 and D1 domains) is mediated by the D1-D2 linker region of its neighboring protomer. In this study we report efforts to better understand this process. Our findings suggest that the amino acid sequence containing Gly-Gly that is located at the C terminus of the D1-D2 linker functions as a pivoting point that allows the dynamic movement of the D1-D2 linker. Furthermore, we found that locking the D1 D2 linker to the D2 domain by introducing disulfide bonds significantly impaired the motion-transmission process. These results support our previous model for interprotomer motion transmission, and provide more detailed information on how the motion transmission between the two ATPase domains of p97 is relayed by the flexible movement of the D1-D2 linker from its neighboring protomer. PMID- 22675117 TI - Attachment of Chlamydia trachomatis L2 to host cells requires sulfation. AB - Chlamydia trachomatis is a pathogen responsible for a prevalent sexually transmitted disease. It is also the most common cause of infectious blindness in the developing world. We performed a loss-of-function genetic screen in human haploid cells to identify host factors important in C. trachomatis L2 infection. We identified and confirmed B3GAT3, B4GALT7, and SLC35B2, which encode glucuronosyltransferase I, galactosyltransferase I, and the 3'-phosphoadenosine 5'-phosphosulfate transporter 1, respectively, as important in facilitating Chlamydia infection. Knockout of any of these three genes inhibits Chlamydia attachment. In complementation studies, we found that the introduction of functional copies of these three genes into the null clones restored full susceptibility to Chlamydia infection. The degree of attachment of Chlamydia strongly correlates with the level of sulfation of the host cell, not simply with the amount of heparan sulfate. Thus, other, as-yet unidentified sulfated macromolecules must contribute to infection. These results demonstrate the utility of screens in haploid cells to study interactions of human cells with bacteria. Furthermore, the human null clones generated can be used to investigate the role of heparan sulfate and sulfation in other settings not limited to infectious disease. PMID- 22675118 TI - Dual disease resistance mediated by the immune receptor Cf-2 in tomato requires a common virulence target of a fungus and a nematode. AB - Plants lack the seemingly unlimited receptor diversity of a somatic adaptive immune system as found in vertebrates and rely on only a relatively small set of innate immune receptors to resist a myriad of pathogens. Here, we show that disease-resistant tomato plants use an efficient mechanism to leverage the limited nonself recognition capacity of their innate immune system. We found that the extracellular plant immune receptor protein Cf-2 of the red currant tomato (Solanum pimpinellifolium) has acquired dual resistance specificity by sensing perturbations in a common virulence target of two independently evolved effectors of a fungus and a nematode. The Cf-2 protein, originally identified as a monospecific immune receptor for the leaf mold fungus Cladosporium fulvum, also mediates disease resistance to the root parasitic nematode Globodera rostochiensis pathotype Ro1-Mierenbos. The Cf-2-mediated dual resistance is triggered by effector-induced perturbations of the apoplastic Rcr3(pim) protein of S. pimpinellifolium. Binding of the venom allergen-like effector protein Gr VAP1 of G. rostochiensis to Rcr3(pim) perturbs the active site of this papain like cysteine protease. In the absence of the Cf-2 receptor, Rcr3(pim) increases the susceptibility of tomato plants to G. rostochiensis, thus showing its role as a virulence target of these nematodes. Furthermore, both nematode infection and transient expression of Gr-VAP1 in tomato plants harboring Cf-2 and Rcr3(pim) trigger a defense-related programmed cell death in plant cells. Our data demonstrate that monitoring host proteins targeted by multiple pathogens broadens the spectrum of disease resistances mediated by single plant immune receptors. PMID- 22675119 TI - Cooperative coupling of cell-matrix and cell-cell adhesions in cardiac muscle. AB - Adhesion between cardiac myocytes is essential for the heart to function as an electromechanical syncytium. Although cell-matrix and cell-cell adhesions reorganize during development and disease, the hierarchical cooperation between these subcellular structures is poorly understood. We reasoned that, during cardiac development, focal adhesions mechanically stabilize cells and tissues during myofibrillogenesis and intercalated disc assembly. As the intercalated disc matures, we postulated that focal adhesions disassemble as systolic stresses are transmitted intercellularly. Finally, we hypothesized that pathological remodeling of cardiac microenvironments induces excessive mechanical loading of intercalated discs, leading to assembly of stabilizing focal adhesions adjacent to the junction. To test our model, we engineered MUtissues composed of two ventricular myocytes on deformable substrates of tunable elasticity to measure the dynamic organization and functional remodeling of myofibrils, focal adhesions, and intercalated discs as cooperative ensembles. Maturing MUtissues increased systolic force while simultaneously developing into an electromechanical syncytium by disassembling focal adhesions at the cell-cell interface and forming mature intercalated discs that transmitted the systolic load. We found that engineering the microenvironment to mimic fibrosis resulted in focal adhesion formation adjacent to the cell-cell interface, suggesting that the intercalated disc required mechanical reinforcement. In these pathological microenvironments, MUtissues exhibited further evidence of maladaptive remodeling, including lower work efficiency, longer contraction cycle duration, and weakened relationships between cytoskeletal organization and force generation. These results suggest that the cooperative balance between cell matrix and cell-cell adhesions in the heart is guided by an architectural and functional hierarchy established during development and disrupted during disease. PMID- 22675120 TI - Water at hydrophobic interfaces delays proton surface-to-bulk transfer and provides a pathway for lateral proton diffusion. AB - Fast lateral proton migration along membranes is of vital importance for cellular energy homeostasis and various proton-coupled transport processes. It can only occur if attractive forces keep the proton at the interface. How to reconcile this high affinity to the membrane surface with high proton mobility is unclear. Here, we tested whether a minimalistic model interface between an apolar hydrophobic phase (n-decane) and an aqueous phase mimics the biological pathway for lateral proton migration. The observed diffusion span, on the order of tens of micrometers, and the high proton mobility were both similar to the values previously reported for lipid bilayers. Extensive ab initio simulations on the same water/n-decane interface reproduced the experimentally derived free energy barrier for the excess proton. The free energy profile G(H(+)) adopts the shape of a well at the interface, having a width of two water molecules and a depth of 6 +/- 2RT. The hydroniums in direct contact with n-decane have a reduced mobility. However, the hydroniums in the second layer of water molecules are mobile. Their in silico diffusion coefficient matches that derived from our in vitro experiments, (5.7 +/- 0.7) 10(-5) cm(2) s(-1). Conceivably, these are the protons that allow for fast diffusion along biological membranes. PMID- 22675121 TI - Reversible voltammograms and a Pourbaix diagram for a protein tyrosine radical. AB - Reversible voltammograms and a voltammetry half-wave potential versus solution pH diagram are described for a protein tyrosine radical. This work required a de novo designed tyrosine-radical protein displaying a unique combination of structural and electrochemical properties. The alpha(3)Y protein is structurally stable across a broad pH range. The redox-active tyrosine Y32 resides in a desolvated and well-structured environment. Y32 gives rise to reversible square wave and differential pulse voltammograms at alkaline pH. The formal potential of the Y32-O(*)/Y32-OH redox couple is determined to 918 +/- 2 mV versus the normal hydrogen electrode at pH 8.40 +/- 0.01. The observation that Y32 gives rise to fully reversible voltammograms translates into an estimated lifetime of >=30 ms for the Y32-O(*) state. This illustrates the range of tyrosine-radical stabilization that a structured protein can offer. Y32 gives rise to quasireversible square-wave and differential pulse voltammograms at acidic pH. These voltammograms represent the Y32 species at the upper edge of the quasirevesible range. The square-wave net potential closely approximates the formal potential of the Y32-O(*)/Y32-OH redox couple to 1,070 +/- 1 mV versus the normal hydrogen electrode at pH 5.52 +/- 0.01. The differential pulse voltammetry half-wave potential of the Y32-O(*)/Y32-OH redox pair is measured between pH 4.7 and 9.0. These results are described and analyzed. PMID- 22675122 TI - Mechanistic basis for low threshold mechanosensitivity in voltage-dependent K+ channels. AB - Living cells respond to mechanical forces applied to their outer membrane through processes referred to as "mechanosensation". Faced with hypotonic shock, to circumvent cell lysis, bacteria open large solute-passing channels to reduce the osmotic pressure gradient. In the vascular beds of vertebrate animals blood flow is regulated directly through mechanical distention-induced opening of stretch activated channels in smooth muscle cells. Touch sensation is thought to originate in mechanically sensitive ion channels in nerve endings, and hearing in mechanically sensitive ion channels located in specialized cells of the ear. While the ubiquity of mechanosensation in living cells is evident, the ion channels underlying the transduction events in vertebrate animals have remained elusive. Here we demonstrate through electrophysiological recordings that voltage dependent K(+) (Kv) channels exhibit exquisite sensitivity to small (physiologically relevant in magnitude) mechanical perturbations of the cell membrane. The demonstrated mechanosensitivity is quantitatively consistent with membrane tension acting on a late-opening transition through stabilization of a dilated pore. This effect causes a shift in the voltage range over which Kv channels open as well as an increase in the maximum open probability. This mechanically induced shift could allow Kv channels and perhaps other voltage dependent ion channels to play a role in mechanosensation. PMID- 22675123 TI - Mode change of millennial CO2 variability during the last glacial cycle associated with a bipolar marine carbon seesaw. AB - Important elements of natural climate variations during the last ice age are abrupt temperature increases over Greenland and related warming and cooling periods over Antarctica. Records from Antarctic ice cores have shown that the global carbon cycle also plays a role in these changes. The available data shows that atmospheric CO(2) follows closely temperatures reconstructed from Antarctic ice cores during these variations. Here, we present new high-resolution CO(2) data from Antarctic ice cores, which cover the period between 115,000 and 38,000 y before present. Our measurements show that also smaller Antarctic warming events have an imprint in CO(2) concentrations. Moreover, they indicate that during Marine Isotope Stage (MIS) 5, the peak of millennial CO(2) variations lags the onset of Dansgaard/Oeschger warmings by 250 +/- 190 y. During MIS 3, this lag increases significantly to 870 +/- 90 y. Considerations of the ocean circulation suggest that the millennial variability associated with the Atlantic Meridional Overturning Circulation (AMOC) undergoes a mode change from MIS 5 to MIS 4 and 3. Ocean carbon inventory estimates imply that during MIS 3 additional carbon is derived from an extended mass of carbon-enriched Antarctic Bottom Water. The absence of such a carbon-enriched water mass in the North Atlantic during MIS 5 can explain the smaller amount of carbon released to the atmosphere after the Antarctic temperature maximum and, hence, the shorter lag. Our new data provides further constraints for transient coupled carbon cycle-climate simulations during the entire last glacial cycle. PMID- 22675124 TI - Asymmetrical roles of zinc fingers in dynamic DNA-scanning process by the inducible transcription factor Egr-1. AB - Egr-1 is an inducible transcription factor that recognizes 9-bp target DNA sites via three zinc finger domains and activates genes in response to cellular stimuli such as synaptic signals and vascular stresses. Using spectroscopic and computational approaches, we have studied structural, dynamic, and kinetic aspects of the DNA-scanning process in which Egr-1 is nonspecifically bound to DNA and perpetually changes its location on DNA. Our NMR data indicate that Egr-1 undergoes highly dynamic domain motions when scanning DNA. In particular, the zinc finger 1 (ZF1) of Egr-1 in the nonspecific complex is mainly dissociated from DNA and undergoes collective motions on a nanosecond timescale, whereas zinc fingers 2 and 3 (ZF2 and ZF3, respectively) are bound to DNA. This was totally unexpected because the previous crystallographic studies of the specific complex indicated that all of Egr-1's three zinc fingers are equally involved in binding to a target DNA site. Mutations that are expected to enhance ZF1's interactions with DNA and with ZF2 were found to reduce ZF1's domain motions in the nonspecific complex suggesting that these interactions dictate the dynamic behavior of ZF1. By experiment and computation, we have also investigated kinetics of Egr-1's translocation between two nonspecific DNA duplexes. Our data on the wild type and mutant proteins suggest that the domain dynamics facilitate Egr-1's intersegment transfer that involves transient bridging of two DNA sites. These results shed light on asymmetrical roles of the zinc finger domains for Egr 1 to scan DNA efficiently in the nucleus. PMID- 22675126 TI - Molecular epidemiology of Aspergillus fumigatus isolates harboring the TR34/L98H azole resistance mechanism. AB - A rapid emergence of azole resistance has been observed in Aspergillus fumigatus in The Netherlands over the past decade. The dominant resistance mechanism appears to be of environmental origin and involves the TR(34)/L98H mutations in cyp51A. This resistance mechanism is now also increasingly being found in other countries. Therefore, genetic markers were used to gain more insights into the origin and spread of this genotype. Studies of 142 European isolates revealed that those with the TR(34)/L98H resistance mechanism showed less genetic variation than azole-susceptible isolates or those with a different genetic basis of resistance and were assigned to only four CSP (putative cell surface protein) types. Sexual crossing experiments demonstrated that TR(34)/L98H isolates could outcross with azole-susceptible isolates of different genetic backgrounds, suggesting that TR(34)/L98H isolates can undergo the sexual cycle in nature. Overall, our findings suggest a common ancestor of the TR(34)/L98H mechanism and subsequent migration of isolates harboring TR(34)/L98H across Europe. PMID- 22675125 TI - Multilocus sequence analysis of isolates of Achromobacter from patients with cystic fibrosis reveals infecting species other than Achromobacter xylosoxidans. AB - A multilocus sequence analysis (MLSA) scheme was developed for characterization of strains and species from the genus Achromobacter, which are increasingly recovered from patients with cystic fibrosis (CF). Five conserved housekeeping genes were selected for the MLSA, which was applied to a diverse collection of 77 strains originating from Europe, Asia, and South America and including type strains of the seven recognized Achromobacter species, six environmental strains, eight non-CF clinical strains, and 56 CF clinical strains. The discriminatory power of MLSA, based on 2,098 nucleotides (nt), was much superior to a 16S rRNA gene comparison based on 1,309 nt. Congruence was observed between single-gene trees and a concatenated gene tree. MLSA differentiated all seven current Achromobacter species and also demonstrated the presence of at least four novel potential species within the genus. CF isolates were predominantly Achromobacter xylosoxidans (64%), an undescribed Achromobacter species (18%), and Achromobacter ruhlandii (7%). A clone of Achromobacter, which has spread among patients from Danish CF centers in Aarhus and Copenhagen, was identified as Achromobacter ruhlandii. MLSA facilitates the specific identification of isolates of Achromobacter necessary for describing their role in clinical infections. PMID- 22675127 TI - Novel approach for detection of hepatitis E virus infection in German blood donors. AB - The risk of transfusion-transmitted hepatitis E virus (HEV) infections by contaminated blood products remains unknown. In the present study, we evaluated and compared different nucleic acid amplification technique (NAT) methods for the detection of HEV in blood components. Minipools of a total of 16,125 individual blood donors were screened for the presence of HEV RNA using the highly sensitive RealStar HEV RT-PCR kit, revealing a minimum detection limit of 4.66 IU/ml. Thirteen donors were HEV RNA positive (0.08%), and of these donors, only three already showed reactive IgM antibody titers. The detected HEV strains all belonged to genotype 3 and were most closely related to German HEV strains from wild boars and pigs as well as from human hepatitis E cases. Furthermore, HEV RNA and HEV-specific IgM and IgG titers were determined in 136 blood donors with elevated alanine aminotransferase (ALT) levels and in 200 donors without pathological findings. HEV RNA was not detectable, but 8.08% (elevated ALT) and 0.5% (nonelevated ALT) of donors showed reactive HEV IgM titers. The overall seroprevalence rate of HEV IgG amounted to 5.94% (elevated ALT, 5.88%; nonelevated ALT, 6.0%). The clinical relevance of transfusion-associated hepatitis E infection still requires further investigation. However, in connection with raising concerns regarding blood safety, our NAT method provides a sensitive possibility for HEV testing. PMID- 22675128 TI - Efficient quantification of HIV-1 in heparin plasma spiked with cultured HIV-1 by the Roche Cobas TaqMan and Abbott RealTime HIV-1 tests. AB - The current automated real-time HIV-1 viral load assays, the Roche Cobas AmpliPrep/Cobas TaqMan test and the Abbott RealTime test, are FDA cleared for use with EDTA plasma. We show that both real-time reverse transcription-PCR (RT-PCR) tests reliably quantify HIV-1 RNA in heparin plasma specimens spiked with HIV-1 isolate MN. PMID- 22675129 TI - Clustered tuberculosis in a low-burden country: nationwide genotyping through 15 years. AB - Molecular genotyping of Mycobacterium tuberculosis has proved to be a powerful tool in tuberculosis surveillance, epidemiology, and control. Based on results obtained through 15 years of nationwide IS6110 restriction fragment length polymorphism (RFLP) genotyping of M. tuberculosis cases in Denmark, a country on the way toward tuberculosis elimination, we discuss M. tuberculosis transmission dynamics and point to areas for control interventions. Cases with 100% identical genotypes (RFLP patterns) were defined as clustered, and a cluster was defined as cases with an identical genotype. Of 4,601 included cases, corresponding to 76% of reported and 97% of culture-verified tuberculosis cases in the country, 56% were clustered, of which 69% were Danes. Generally, Danes were more often in large clusters (>= 50 persons), older (mean age, 45 years), and male (male/female ratio, 2.5). Also, Danes had a higher cluster frequency within a 2-year observation window (60.8%), and higher clustering rate of new patterns over time, compared to immigrants. A dominant genotype, cluster 2, constituted 44% of all clustered and 35% of all genotyped cases. This cluster was primarily found among Danish males, 30 to 59 years of age, often socially marginalized, and with records of alcohol abuse. In Danes, cluster 2 alone was responsible for the high cluster frequency level. Immigrants had a higher incidence of clustered tuberculosis at a younger age (0 to 39 years). To achieve tuberculosis elimination in Denmark, high-risk transmission environments, like the cluster 2 environment in Danes, and specific transmission chains in immigrants in the capital area, e.g., homeless/socially marginalized Somalis/Greenlanders, often with alcohol abuse, must be targeted, including groups with a high risk of reactivation. PMID- 22675130 TI - Prosthetic valve endocarditis caused by a Pasteurella dagmatis-like isolate originating from a patient's cat. AB - Pasteurella species are part of the oral flora of cats and dogs. In humans, they are frequently found in infected animal bite wounds, but invasive infections are rare. This is the first report of prosthetic-valve endocarditis with a Pasteurella dagmatis-like species, which originated from the patient's cat. PMID- 22675131 TI - Duration of hospital admission and the need for empirical antipseudomonal therapy. AB - To reduce selective pressure for antimicrobial resistance, empirical use of antipseudomonal antibiotics is often reserved for patients with late-onset hospital-acquired infections. We examined the likelihood of isolating Pseudomonas aeruginosa as a function of time from hospital admission. We conducted a retrospective cohort study of all positive bacterial cultures in a tertiary-care hospital between March 2010 and November 2011. The primary outcome was the proportion of positive cultures yielding P. aeruginosa. Multivariable logistic regression was employed to assess the impact of time from admission on the likelihood of isolating P. aeruginosa, after adjusting for other important risk factors. A total of 7,668 positive cultures were obtained from 4,108 unique patients during the study interval, including 633 (8.3%) yielding P. aeruginosa. The probability of isolating P. aeruginosa increased linearly from 79/2,044 (3.9%) positive cultures obtained on admission to 153/664 (23%) in the 10th week of admission or beyond. The unadjusted odds ratio was 1.002/day (95% confidence interval [CI], 1.0016 to 1.0028; P < 0.0001); the adjusted odds ratio (aOR) was 1.0007/day (95% CI, 1.0001 to 1.0013; P = 0.02). Other important predictors of P. aeruginosa isolation included respiratory specimen type (aOR, 13.8; 95% CI, 9.1 to 21.1), recent hospital admission (aOR,1.8; 95% CI, 1.4 to 2.3), prior P. aeruginosa isolation during current admission (aOR, 4.9; 95% CI, 3.7 to 6.4), and prior antipseudomonal (aOR, 1.9; 95% CI, 1.4 to 2.5) or nonantipseudomonal (aOR, 1.8; 95% CI, 1.4 to 2.4) antibiotic exposure. It was determined that as time from admission increases, there is a linear increase in the likelihood of P. aeruginosa isolation. Any guidelines which distinguish early from late hospital acquired infection must consider the implications of time point selection on the likelihood of inadequate P. aeruginosa empirical coverage. PMID- 22675132 TI - Differential detection of avian oncogenic viruses in poultry layer farms and Turkeys by use of multiplex PCR. AB - Avian oncogenic viruses include Marek's disease virus (MDV), a highly contagious herpesvirus, as well as retroviruses such as avian leukosis virus (ALV) subgroups A to J and reticuloendotheliosis virus (REV). In this study, we examined the incidence of these viruses in suspected samples collected from poultry layer farms of South India, mainly in the Namakkal district of Tamil Nadu, a highly dense poultry-growing area in India. The histopathology-positive tissue sections were identified and further confirmed by immunohistochemistry using virus specific antibodies. The viruses belonging to all 3 groups (MDV, ALV, and REV) were isolated in a cell culture system and confirmed by immunofluorescence using virus-specific antibodies. PCR appeared to be the method of choice for rapid and accurate diagnosis of these viruses. The multiplex PCR primers specific to MDV, ALV, REV, and chicken DNA were designed for rapid differential diagnosis. The specificity of the primers was checked by amplification of DNA from virus infected cell culture in comparison with uninfected samples, and sensitivity was evaluated by calculating the minimum copy number at which amplification occurs in the cloned PCR products. The sequences of the amplicons were compared by BLAST analysis. PCR tests demonstrated the presence of single, dual, or triple viruses in some of the samples. Of 169 samples screened by multiplex PCR, 9 samples were positive for MDV, 17 samples were positive for ALV, 12 samples were positive for REV, and 17 samples were positive for both ALV and REV. Three samples were positive for all three viruses. ALV-positive samples were further subjected to subgroup-specific PCR, which gave positive results for subgroups B and D but not for subgroup J. Multiplex PCR appeared to be a useful technique for rapid differential diagnosis of avian oncogenic viruses and detection of multiple infections of avian oncogenic viruses under field conditions. PMID- 22675133 TI - Prosthetic valve endocarditis due to Neisseria skkuensis, a novel Neisseria species. AB - We describe the first reported case of endocarditis due to Neisseria skkuensis. The organism from the blood cultures taken on admission day was identified initially as unidentified Gram-negative cocci by Vitek2. Finally, it was identified as Neisseria skkuensis by 16 rRNA gene sequence analysis. PMID- 22675134 TI - Automated detection of toxigenic Clostridium difficile in clinical samples: isothermal tcdB amplification coupled to array-based detection. AB - Clostridium difficile can carry a genetically variable pathogenicity locus (PaLoc), which encodes clostridial toxins A and B. In hospitals and in the community at large, this organism is increasingly identified as a pathogen. To develop a diagnostic test that combines the strengths of immunoassays (cost) and DNA amplification assays (sensitivity/specificity), we targeted a genetically stable PaLoc region, amplifying tcdB sequences and detecting them by hybridization capture. The assay employs a hot-start isothermal method coupled to a multiplexed chip-based readout, creating a manual assay that detects toxigenic C. difficile with high sensitivity and specificity within 1 h. Assay automation on an electromechanical instrument produced an analytical sensitivity of 10 CFU (95% probability of detection) of C. difficile in fecal samples, along with discrimination against other enteric bacteria. To verify automated assay function, 130 patient samples were tested: 31/32 positive samples (97% sensitive; 95% confidence interval [CI], 82 to 99%) and 98/98 negative samples (100% specific; 95% CI, 95 to 100%) were scored correctly. Large-scale clinical studies are now planned to determine clinical sensitivity and specificity. PMID- 22675135 TI - Faunal isotope records reveal trophic and nutrient dynamics in twentieth century Yellowstone grasslands. AB - Population sizes and movement patterns of ungulate grazers and their predators have fluctuated dramatically over the past few centuries, largely owing to overharvesting, land-use change and historic management. We used delta(13)C and delta(15)N values measured from bone collagen of historic and recent gray wolves and their potential primary prey from Yellowstone National Park to gain insight into the trophic dynamics and nutrient conditions of historic and modern grasslands. The diet of reintroduced wolves closely parallels that of the historic population. We suggest that a significant shift in faunal delta(15)N values over the past century reflects impacts of anthropogenic environmental changes on grassland ecosystems, including grazer-mediated shifts in grassland nitrogen cycle processes. PMID- 22675136 TI - Cool running: locomotor performance at low body temperature in mammals. AB - Mammalian torpor saves enormous amounts of energy, but a widely assumed cost of torpor is immobility and therefore vulnerability to predators. Contrary to this assumption, some small marsupial mammals in the wild move while torpid at low body temperatures to basking sites, thereby minimizing energy expenditure during arousal. Hence, we quantified how mammalian locomotor performance is affected by body temperature. The three small marsupial species tested, known to use torpor and basking in the wild, could move while torpid at body temperatures as low as 14.8-17.9 degrees C. Speed was a sigmoid function of body temperature, but body temperature effects on running speed were greater than those in an ectothermic lizard used for comparison. We provide the first quantitative data of movement at low body temperature in mammals, which have survival implications for wild heterothermic mammals, as directional movement at low body temperature permits both basking and predator avoidance. PMID- 22675137 TI - Live-bearing manta ray: how the embryo acquires oxygen without placenta and umbilical cord. AB - We conducted an ultrasonographic experiment on a pregnant manta ray, Manta alfredi (Chondrichthyes, Batoidea). This study showed how the embryo of the live bearing elasmobranchs respires in the body of the female. In the embryonic stage, the manta ray embryo takes in uterine fluid by buccal-pumping. After birth, the manta ray shifts its respiratory mode from buccal-pumping to ram-ventilation. The rapid reduction of the spiracle size in the young manta ray may reflect this shift of respiratory mode. Unlike mammals or some carcharhinid sharks that acquire oxygen through a placenta and umbilical cord, the manta ray embryo does not have a direct connection with the mother. Thus, the manta ray embryo obtains oxygen by buccal-pumping of the uterine fluid, in the same way that the embryos of egg-laying species obtain oxygen from the water in the egg case. This finding extends our understanding of the diversity of embryonic respiratory systems in live-bearing vertebrates. PMID- 22675138 TI - Deceptive vibratory communication: pupae of a beetle exploit the freeze response of larvae to protect themselves. AB - It is argued that animal signals may have evolved so as to manipulate the response of receivers in a way that increases the fitness of the signallers. In deceptive communication, receivers incur costs by responding to false signals. Recently, we reported that pupae of the soil-inhabiting Japanese rhinoceros beetle Trypoxylus dichotoma produce vibratory signals to deter burrowing larvae, thereby protecting themselves. In the present study, monitoring of vibrations associated with larval movement revealed that T. dichotoma larvae remained motionless for ca 10 min when pupal vibratory signals were played back transiently (freeze response). Furthermore, pupal signals of T. dichotoma elicited a freeze response in three other scarabaeid species, whose pupae do not produce vibratory signals. This indicates that the freeze response to certain types of vibration evolved before the divergence of these species and has been evolutionarily conserved, presumably because of the fitness advantage in avoiding predators. Pupae of T. dichotoma have probably exploited pre-existing anti predator responses of conspecific larvae to protect themselves by emitting deceptive vibratory signals. PMID- 22675139 TI - Biological invasions and the acoustic niche: the effect of bullfrog calls on the acoustic signals of white-banded tree frogs. AB - Invasive species are known to affect native species in a variety of ways, but the effect of acoustic invaders has not been examined previously. We simulated an invasion of the acoustic niche by exposing calling native male white-banded tree frogs (Hypsiboas albomarginatus) to recorded invasive American bullfrog (Lithobates catesbeianus) calls. In response, tree frogs immediately shifted calls to significantly higher frequencies. In the post-stimulus period, they continued to use higher frequencies while also decreasing signal duration. Acoustic signals are the primary basis of mate selection in many anurans, suggesting that such changes could negatively affect the reproductive success of native species. The effects of bullfrog vocalizations on acoustic communities are expected to be especially severe due to their broad frequency band, which masks the calls of multiple species simultaneously. PMID- 22675140 TI - Wildlife-friendly farming benefits rare birds, bees and plants. AB - Agricultural intensification is a leading cause of global biodiversity loss, especially for threatened and near-threatened species. One widely implemented response is 'wildlife-friendly farming', involving the close integration of conservation and extensive farming practices within agricultural landscapes. However, the putative benefits from this controversial policy are currently either unknown or thought unlikely to extend to rare and declining species. Here, we show that new, evidence-based approaches to habitat creation on intensively managed farmland in England can achieve large increases in plant, bee and bird species. In particular, we found that habitat enhancement methods designed to provide the requirements of sensitive target biota consistently increased the richness and abundance of both rare and common species, with 10-fold to greater than 100-fold more rare species per sample area than generalized conventional conservation measures. Furthermore, targeting landscapes of high species richness amplified beneficial effects on the least mobile taxa: plants and bees. Our results provide the first unequivocal support for a national wildlife-friendly farming policy and suggest that this approach should be implemented much more extensively to address global biodiversity loss. However, to be effective, these conservation measures must be evidence-based, and developed using sound knowledge of the ecological requirements of key species. PMID- 22675141 TI - Minimum convex hull mass estimations of complete mounted skeletons. AB - Body mass is a critical parameter used to constrain biomechanical and physiological traits of organisms. Volumetric methods are becoming more common as techniques for estimating the body masses of fossil vertebrates. However, they are often accused of excessive subjective input when estimating the thickness of missing soft tissue. Here, we demonstrate an alternative approach where a minimum convex hull is derived mathematically from the point cloud generated by laser scanning mounted skeletons. This has the advantage of requiring minimal user intervention and is thus more objective and far quicker. We test this method on 14 relatively large-bodied mammalian skeletons and demonstrate that it consistently underestimates body mass by 21 per cent with minimal scatter around the regression line. We therefore suggest that it is a robust method of estimating body mass where a mounted skeletal reconstruction is available and demonstrate its usage to predict the body mass of one of the largest, relatively complete sauropod dinosaurs: Giraffatitan brancai (previously Brachiosaurus) as 23200 kg. PMID- 22675142 TI - Successful use of allopurinol in a patient on dialysis. AB - We report the case of a man with chronic tophaceous gout who had end-stage renal failure secondary to the Alport syndrome. Following a failed kidney transplant, where urate deposition was a suspected contributor, the patient responded positively to consistent allopurinol therapy and regular haemodialysis sessions. Extensive and destructive tophi receded in size remarkably and the almost constant incidence of acute attacks of gout subsided. The patient has recently received a new kidney transplant and his plasma concentrations of urate are controlled well with allopurinol and he no longer experiences acute attacks of gout. While efficacious, adherence is critical for achieving the therapeutic effects of allopurinol even in end-stage renal disease. PMID- 22675143 TI - Whipple's disease presenting with neurological symptoms in an immunosuppressed patient. AB - We report an unusual case of Whipple's disease, which remained undiagnosed for several years in a patient being treated with immunosuppressive therapy for many years. The patient presented with a purpuric rash, neurological symptoms, lymphadenopathy and gastrointestinal symptoms. The diagnosis was made by endoscopic biopsy of the duodenum with periodic acid Schiff staining, as well as PCR testing on blood and cerebrospinal fluid. The patient was successfully treated with intravenous ceftriaxone, followed by oral co-trimoxazole for 1 year. PMID- 22675144 TI - Gastric GIST with synchronous neuroendocrine tumour of the pancreas in a patient without neurofibromatosis type 1. AB - The gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the gastrointestinal tract. These are rare tumours with an incidence of 15 new cases per million per year. The occurrence of neuroendocrine tumours of the pancreas is rare, representing 1-5% of pancreatic cancers, and it is estimated that its incidence does not exceed five to one million. GISTs are common in patients with neurofibromatosis type 1 (NF1); there are few reported cases of synchronous neuroendocrine tumours in these patients and most are pheochromocytomas. The case reports a 64-year-old woman referred to the General Surgery Outpatient for incidental finding of gastric and pancreatic tumours. She underwent a radical subtotal pancreatectomy + partial gastrectomy with jejunal transposition. The pathological examination revealed: gastric GISTs and a well differentiated neuroendocrine carcinoma of the pancreas. This is the second case published so far of a patient with both tumours and without NF1. Posterior studies must be performed to evaluate if some other genetic disorder is involved in these patients without NF1. PMID- 22675145 TI - One heart, two cardiomyopathies. AB - A 63-year-old woman with no previous medical problems presented with acute chest pain and an ECG consistent with an acute anterior myocardial infarction. At emergency angiography, she was found to have smooth unobstructed coronary arteries. On invasive left ventriculography, overall poor systolic function was noted with apical hypokinesis and basal hyperkinesis, consistent with Tako-tsubo phenomenon. Echocardiography demonstrated a hypertrophic left ventricle and left ventricular outflow obstruction due to systolic anterior motion of the mitral valve and moderate mitral regurgitation. Following appropriate management, she was discharged 6 days later. An outpatient MRI confirmed normalisation of the left ventricular systolic function; however, there was still significant left ventricular hypertrophy and dynamic obstruction. Although most patients presenting with chest pain and an ECG with ST elevation will have an acute coronary event, our patient had normal coronaries but both Tako-tsubo and hypertrophic cardiomyopathies. PMID- 22675146 TI - Frontal sinus mucoceles presenting in the upper eyelid: an easily missed diagnosis. AB - Frontal sinus mucoceles are epithelium-lined mucus-containing sacs that are capable of bony expansion causing a spectrum of ophthalmological symptoms. If left untreated, they can erode the thin sinus wall causing life-threatening complications such as meningitis. We would like to alert the clinicians to this diagnosis that can be easily misdiagnosed. The first patient appeared to have an allergic blepharo-conjunctivitis that was not responding to topical and systemic medications. The second patient presented with recurrent preseptal cellulitis unresponsive to oral antibiotics. CT imaging of both patients revealed frontal sinus mucoceles. Both patients recovered well with sinus surgery. Management of these patients needed a close liaison with our ENT and radiology colleagues to warrant a good outcome. PMID- 22675147 TI - Massive calcium channel blocker overdose: intravenous insulin and glucose as a therapy. AB - We describe a case of massive overdosage with cardiac medications that proved resistant to conventional support, including fluid replacement, inotropes, mechanical ventilation, cardiac pacing and haemofiltration. The use of a high dose insulin and glucose infusion proved to be beneficial in the acute management although the patient has been left with significant impairment of cardiac function. PMID- 22675148 TI - A kind of specific osteolytic destruction of the vertebral bodies. AB - This report describes two young patients with osteolytic destruction in two adjacent vertebral bodies along with the intervertebral disc, and reveals its possible mechanism. A lateral radiograph and CT scan displayed a giant osteolytic cavity in the L4 vertebral body. An MRI or CT scan with a two-dimensional reconstruction displayed the same changes in the L4 vertebral body and lower endplate erosion in the L3 vertebral body. A comprehensive preoperative evaluation did not identify a specific cause of vertebral destruction. Both patients underwent anterior lumbar fusion surgery. The lesions were removed for histological and immunohistochemical examination. Histopathological study of the destructed vertebral bodies in the two patients revealed the disruption or atrophy of bone trabeculae with infiltration of a large amount of B-lymphocytes and macrophages into the marrow cavities. Studies of its pathogenesis reveal that it is likely to be a B-lymphocyte-mediated local immune inflammatory reaction in the lumbar spine. PMID- 22675149 TI - Recurrent 'universal tumour' of the spinal cord. AB - Lipoma is popularly known as the 'universal tumour' because of its ubiquitous presence anywhere in the body. This is the first documented case of recurrent thoracic spinal cord intramedullary lipoma in a 44-year-old man, with a background of spinal dysraphism, which recurred 15 years after initial surgery. He was followed up every 2 years and currently presented with an 8-month history of progressive weakness in his lower limbs. An MRI of the spine confirmed recurrence of lipoma. He underwent redo laminectomy and partial resection and spinal cord decompression with duroplasty. Lipoma, although a low-grade tumour, can cause significant neurological deficits because of its location. Surgical exploration and removal of lipoma is recommended. However, to preserve the functionality of the spinal cord, one may resort to partial resection and aim for spinal cord decompression. The literature on spinal cord lipoma is reviewed and the aetiopathogenesis of this rare occurrence is described. PMID- 22675151 TI - Clostridium septicum infection in a young pregnant patient. AB - This report describes a young pregnant woman who presented to a rural emergency department with vaginal bleeding at 7 weeks of gestation. Initially, the patient was stable; however, within 8 h the patient deteriorated into fulminant septic shock. She required aggressive resuscitation and surgical management of a septic abortion. The patient's condition improved rapidly following surgical evacuation of the uterus with dilatation and curettage. She has had no long-term sequelae. Blood and tissue cultures returned positive for Clostridium septicum. To the best of our knowledge, this is the only reported case of survival from C septicum infection in a pregnant woman and highlights the importance of improved awareness and management of such infections by the medical community so that future cases can achieve similarly successful outcomes. PMID- 22675150 TI - Laparoscopic cholecystectomy in situs inversus: points of technique. AB - Laparoscopic cholecystectomy is one of the most common surgical procedures carried out in the world today. Rarely do patients present with undiagnosed situs inversus with cholecystitis. Symptomatic gallstones in patients with situs inversus pose diagnostic and therapeutic challenges. We had one such patient who presented with episodes of pain in the left upper abdomen. She was found to be suffering from situs inversus with gallstones in a left-sided gall bladder. After thorough preoperative evaluation, we performed laparoscopic cholecystectomy by modifying the operative technique adopting a mirror image of port placement on the left side using the left subcostal port (5 mm) for dissection with the right hand and the subxiphoid port for retraction of Hartmann's pouch by the left hand of the surgeon. We can summarise that laparoscopic cholecystectomy in patients of situs inversus can be safely performed by an experienced surgeon. PMID- 22675152 TI - Wunderlich's syndrome (spontaneous renal haemorrhage). AB - Wunderlich's syndrome is a rare condition characterised by spontaneous non traumatic renal haemorrhage into the subcapsular and perirenal space. The commonest cause of Wunderlich's syndrome is renal neoplasms, with angiomyolipoma and renal cell carcinoma being the most common benign and malignant lesions, respectively. We report a case of Wunderlich's syndrome in a 46-year-old woman. She presented in the emergency department with the chief complaints of sudden onset of abdominal pain with no significant medical history. Imaging findings and clinical history led to the diagnosis of Wunderlich's syndrome. The patient underwent left partial nephrectomy and recovered without any complications. She is presently doing well. PMID- 22675153 TI - Recurrent retroperitoneal liposarcoma in a patient with neurofibromatosis type I. AB - INTRODUCTION: Liposarcoma complicating neurofibromatosis is very rare. Only a few cases have been described until now. We present a case of recurrent dedifferentiated retroperitoneal liposarcoma in a patient with neurofibromatosis type I (NF-1). CASE PRESENTATION: A 47-year-old Caucasian woman with NF-1 presented to the hospital initially complaining of left lumbar pain irradiating to the anterior thigh and knee. Physical examination showed atrophy of the lower extremities bilaterally and decreased motor strength on the left lower extremity. Radiological studies demonstrated an enhancing lesion in the left paraspinal region, suggesting malignancy. The patient underwent local resection of tumour with safety margins. Pathological examination was consistent with dedifferentiated liposarcoma (DDLS) with positivity for MDM2 and CDK4 markers. No evidence of metastasis was noted on the radiological studies. The final diagnosis was DDLS, high-grade (G3), pT2bN0M0, stage III. After 6 weeks post-tumour resection, the patient experienced recurrence of malignancy. Chemotherapy with cisplatin and doxorubicin was initiated in the patient. CONCLUSIONS: Liposarcoma in the context of neurofibromatosis is very rare. To the best of our knowledge, only six cases have been reported until now in the literature. We are presenting this case to underline the possibility of recurrence in the case of retroperitoneal DDLSs despite local tumour resection. Also, although the role of chemotherapy is controversial we decided to start treatment with cisplatin and doxorubicin given the success of chemotherapy in similar case presentations. PMID- 22675154 TI - Assessment of HIV-1 patient recruitability in the Republic of Guinea-Bissau using African versus North American hematology and biochemistry reference intervals. AB - Hematology and biochemistry reference intervals have been derived from healthy, HIV-negative populations to guide clinical trials worldwide. However, it is less clear how such values may be applied to clinical trials involving HIV-infected individuals. We show that contradictory interpretations about patient recruitability are reached when applying African versus North American reference intervals to an HIV-1 cohort in Guinea-Bissau. These observations underscore the need to question non-African guidelines in the context of HIV intervention clinical trials in Africa. PMID- 22675155 TI - Validation of an immunodiagnostic assay for detection of 13 Streptococcus pneumoniae serotype-specific polysaccharides in human urine. AB - To improve the clinical diagnosis of pneumococcal infection in bacteremic and nonbacteremic community-acquired pneumonia (CAP), a Luminex technology-based multiplex urinary antigen detection (UAD) diagnostic assay was developed and validated. The UAD assay can simultaneously detect 13 different serotypes of Streptococcus pneumoniae by capturing serotype-specific S. pneumoniae polysaccharides (PnPSs) secreted in human urine. Assay specificity is achieved by capturing the polysaccharides with serotype-specific monoclonal antibodies (MAbs) on spectrally unique microspheres. Positivity for each serotype was based on positivity cutoff values calculated from a standard curve run on each assay plate together with positive- and negative-control urine samples. The assay is highly specific, since significant signals are detected only when each PnPS was paired with its homologous MAb-coated microspheres. Validation experiments demonstrated excellent accuracy and precision. The UAD assay and corresponding positivity cutoff values were clinically validated by assessing 776 urine specimens obtained from patients with X-ray-confirmed CAP. The UAD assay demonstrated 97% sensitivity and 100% specificity using samples obtained from patients with bacteremic, blood culture-positive CAP. Importantly, the UAD assay identified Streptococcus pneumoniae (13 serotypes) in a proportion of individuals with nonbacteremic CAP, a patient population for which the pneumococcal etiology of CAP was previously difficult to assess. Therefore, the UAD assay provides a specific, noninvasive, sensitive, and reproducible tool to support vaccine efficacy as well as epidemiological evaluation of pneumococcal disease, including CAP, in adults. PMID- 22675156 TI - Abnormal immune responses in persons with previous extrapulmonary tuberculosis in an in vitro model that simulates in vivo infection with Mycobacterium tuberculosis. AB - Persons with previous extrapulmonary tuberculosis have reduced peripheral blood mononuclear cell cytokine production and CD4(+) lymphocytes compared to persons with previous pulmonary tuberculosis or latent tuberculosis infection, but specific defects related to Mycobacterium tuberculosis infection of macrophages have not been characterized. The objective of this study was to further characterize the in vitro immune responses to M. tuberculosis infection in HIV seronegative persons with previous extrapulmonary tuberculosis. Peripheral blood mononuclear cells were isolated from HIV-seronegative persons with previous extrapulmonary tuberculosis (n = 11), previous pulmonary tuberculosis (n = 21), latent M. tuberculosis infection (n = 19), and uninfected tuberculosis contacts (n = 20). Experimental conditions included M. tuberculosis-infected macrophages cultured with and without monocyte-depleted peripheral blood mononuclear cells. Concentrations of interleukin 1beta (IL-1beta), IL-4, IL-6, CXCL8 (IL-8), IL-10, IL-12p70, IL-17, CCL2 (monocyte chemoattractant protein 1), tumor necrosis factor alpha (TNF-alpha), and gamma interferon (IFN-gamma) were measured by multiplex cytokine array. When M. tuberculosis-infected macrophages were cocultured with monocyte-depleted peripheral blood mononuclear cells, IFN-gamma (P = 0.01), TNF alpha (P = 0.04), IL-10 (P < 0.001), and IL-6 (P = 0.03) exhibited similar continua of responses, with uninfected persons producing the lowest levels, followed by extrapulmonary tuberculosis cases, pulmonary tuberculosis controls, and persons with latent M. tuberculosis infection. A similar pattern was observed with CXCL8 (P = 0.04), IL-10 (P = 0.02), and CCL2 (P = 0.03) when monocyte depleted peripheral blood mononuclear cells from the four groups were cultured alone. Persons with previous extrapulmonary tuberculosis had decreased production of several cytokines, both at rest and after stimulation with M. tuberculosis. Our results suggest that persons who develop extrapulmonary tuberculosis have a subtle global immune defect that affects their response to M. tuberculosis infection. PMID- 22675157 TI - The effect of prenatal highly active antiretroviral therapy on the transmission of congenital and perinatal/early postnatal cytomegalovirus among HIV-infected and HIV-exposed infants. AB - BACKGROUND: Before highly active antiretroviral therapy (HAART), congenital cytomegalovirus (CMV) rates were higher among human immunodeficiency virus (HIV) exposed infants than unexposed infants. This study examines congenital and perinatal/early postnatal (P/EP) CMV among HIV-exposed infants pre- and post- HAART. METHODS: Infants born to HIV-infected women were evaluated for congenital CMV (CMV-positive culture in first 3 weeks of life) and P/EP CMV (positive culture in first 6 months of life). Prenatal maternal HAART was defined as triple antiretroviral therapy (ART) with at least 1 nonnucleoside reverse-transcriptase inhibitor or protease inhibitor. RESULTS: Among 414 infants evaluated, 1678 CMV assessment days were completed (mean = 3 assessment days per infant). Congenital CMV rates did not differ by time period, HAART use, or infant HIV infection status. P/EP CMV rates were greater for the 1988-1996 birth cohort (17.9%) compared with the 1997-2002 birth cohort (8.9%) (P < .01), HIV-infected versus uninfected infants (P < .01), and infants with no maternal ART versus those with ART (P < .01). Controlling for potential confounders, P/EP CMV was associated with no maternal ART (odds ratio = 4.7; P < .01), and among those with no maternal ART, P/EP CMV was associated with maternal CD4 count <=200 cells/MUL (P < .01). For HIV-uninfected infants with P/EP CMV, symptoms including splenomegaly, lymphadenopathy, and hepatomegaly were associated with no maternal HAART versus those with HAART (41% vs 6%; P < .05). CONCLUSIONS: Although congenital CMV rates did not change, the post-HAART era showed reduced P/EP CMV and occurrence of related clinical symptoms. These findings underscore the importance of prenatal HAART for all HIV-infected pregnant women. PMID- 22675158 TI - Coarctation of the aorta and coronary artery disease: fact or fiction? AB - BACKGROUND: Aortic coarctation (CoA) is reported to predispose to coronary artery disease (CAD). However, our clinical observations do not support this premise. Our objectives were to describe the prevalence of CAD among adults with CoA and to determine whether CoA is an independent predictor of CAD or premature CAD. METHODS AND RESULTS: The study population was derived from the Quebec Congenital Heart Disease Database. We compared patients with CoA and those with a ventricular septal defect, who are not known to be at increased risk of CAD. The prevalence of CAD in patients with CoA compared with those with ventricular septal defect was determined. We then used a nested case-control design to determine whether CoA independently predicted for the development of CAD. Of 756 patients with CoA who were alive in 2005, 37 had a history of CAD compared with 224 of 6481 patients with ventricular septal defect (4.9% versus 3.5%; P=0.04). Male sex (odds ratio [OR], 2.13; 95% confidence interval [CI], 1.62-2.80), hypertension (OR, 1.95; 95% CI, 1.44-2.64), diabetes mellitus (OR, 1.68; 95% CI, 1.09-2.58), age (OR per 10-year increase, 2.28; 95% CI, 2.09-2.48), and hyperlipidemia (OR, 11.58; 95% CI, 5.75-23.3) all independently predicted for the development of CAD. CoA did not independently predict for the development of CAD (OR, 1.04; 95% CI, 0.68-1.57) or premature CAD (OR for CoA versus ventricular septal defect, 1.44; 95% CI, 0.79-2.64) after adjustment for other factors. CONCLUSIONS: Although traditional cardiovascular risk factors independently predicted for the development of CAD, the diagnosis of CoA alone did not. Our findings suggest that cardiovascular outcomes of these patients may be improved with tight risk factor control. PMID- 22675159 TI - Aortic coarctation and coronary artery disease: the XY factor. PMID- 22675160 TI - Strain amplification in bone mechanobiology: a computational investigation of the in vivo mechanics of osteocytes. AB - The osteocyte is believed to act as the main sensor of mechanical stimulus in bone, controlling signalling for bone growth and resorption in response to changes in the mechanical demands placed on our bones throughout life. However, the precise mechanical stimuli that bone cells experience in vivo are not yet fully understood. The objective of this study is to use computational methods to predict the loading conditions experienced by osteocytes during normal physiological activities. Confocal imaging of the lacunar-canalicular network was used to develop three-dimensional finite element models of osteocytes, including their cell body, and the surrounding pericellular matrix (PCM) and extracellular matrix (ECM). We investigated the role of the PCM and ECM projections for amplifying mechanical stimulation to the cells. At loading levels, representing vigorous physiological activity (3000 uepsilon), our results provide direct evidence that (i) confocal image-derived models predict 350-400% greater strain amplification experienced by osteocytes compared with an idealized cell, (ii) the PCM increases the cell volume stimulated more than 3500 uepsilon by 4-10% and (iii) ECM projections amplify strain to the cell by approximately 50-420%. These are the first confocal image-derived computational models to predict osteocyte strain in vivo and provide an insight into the mechanobiology of the osteocyte. PMID- 22675161 TI - Nanoscale characterization of the biomechanical hardening of bovine zona pellucida. AB - The zona pellucida (ZP) is an extracellular membrane surrounding mammalian oocytes. The so-called zona hardening plays a key role in fertilization process, as it blocks polyspermy, which may also be caused by an increase in the mechanical stiffness of the ZP membrane. However, structural reorganization mechanisms leading to ZP's biomechanical hardening are not fully understood yet. Furthermore, a correct estimate of the elastic properties of the ZP is still lacking. Therefore, the aim of the present study was to investigate the biomechanical behaviour of ZP membranes extracted from mature and fertilized bovine oocytes to better understand the mechanisms involved in the structural reorganization of the ZP that may lead to the biomechanical hardening of the ZP. For that purpose, a hybrid procedure is developed by combining atomic force microscopy nanoindentation measurements, nonlinear finite element analysis and nonlinear optimization. The proposed approach allows us to determine the biomechanical properties of the ZP more realistically than the classical analysis based on Hertz's contact theory, as it accounts for the nonlinearity of finite indentation process, hyperelastic behaviour and material heterogeneity. Experimental results show the presence of significant biomechanical hardening induced by the fertilization process. By comparing various hyperelastic constitutive models, it is found that the Arruda-Boyce eight-chain model best describes the biomechanical response of the ZP. Fertilization leads to an increase in the degree of heterogeneity of membrane elastic properties. The Young modulus changes sharply within a superficial layer whose thickness is related to the characteristic distance between cross-links in the ZP filamentous network. These findings support the hypothesis that biomechanical hardening of bovine ZP is caused by an increase in the number of inter-filaments cross-links whose density should be higher in the ZP inner side. PMID- 22675163 TI - Transmission, attenuation and reflection of shear waves in the human brain. AB - Traumatic brain injuries (TBIs) are caused by acceleration of the skull or exposure to explosive blast, but the processes by which mechanical loads lead to neurological injury remain poorly understood. We adapted motion-sensitive magnetic resonance imaging methods to measure the motion of the human brain in vivo as the skull was exposed to harmonic pressure excitation (45, 60 and 80 Hz). We analysed displacement fields to quantify the transmission, attenuation and reflection of distortional (shear) waves as well as viscoelastic material properties. Results suggest that internal membranes, such as the falx cerebri and the tentorium cerebelli, play a key role in reflecting and focusing shear waves within the brain. The skull acts as a low-pass filter over the range of frequencies studied. Transmissibility of pressure waves through the skull decreases and shear wave attenuation increases with increasing frequency. The skull and brain function mechanically as an integral structure that insulates internal anatomic features; these results are valuable for building and validating mathematical models of this complex and important structural system. PMID- 22675162 TI - Immunofluorescence-guided atomic force microscopy to measure the micromechanical properties of the pericellular matrix of porcine articular cartilage. AB - The pericellular matrix (PCM) is a narrow region that is rich in type VI collagen that surrounds each chondrocyte within the extracellular matrix (ECM) of articular cartilage. Previous studies have demonstrated that the chondrocyte micromechanical environment depends on the relative properties of the chondrocyte, its PCM and the ECM. The objective of this study was to measure the influence of type VI collagen on site-specific micromechanical properties of cartilage in situ by combining atomic force microscopy stiffness mapping with immunofluorescence imaging of PCM and ECM regions in cryo-sectioned tissue samples. This method was used to test the hypotheses that PCM biomechanical properties correlate with the presence of type VI collagen and are uniform with depth from the articular surface. Control experiments verified that immunolabelling did not affect the properties of the ECM or PCM. PCM biomechanical properties correlated with the presence of type VI collagen, and matrix regions lacking type VI collagen immediately adjacent to the PCM exhibited higher elastic moduli than regions positive for type VI collagen. PCM elastic moduli were similar in all three zones. Our findings provide further support for type VI collagen in defining the chondrocyte PCM and contributing to its biological and biomechanical properties. PMID- 22675164 TI - Modelling cell motility and chemotaxis with evolving surface finite elements. AB - We present a mathematical and a computational framework for the modelling of cell motility. The cell membrane is represented by an evolving surface, with the movement of the cell determined by the interaction of various forces that act normal to the surface. We consider external forces such as those that may arise owing to inhomogeneities in the medium and a pressure that constrains the enclosed volume, as well as internal forces that arise from the reaction of the cells' surface to stretching and bending. We also consider a protrusive force associated with a reaction-diffusion system (RDS) posed on the cell membrane, with cell polarization modelled by this surface RDS. The computational method is based on an evolving surface finite-element method. The general method can account for the large deformations that arise in cell motility and allows the simulation of cell migration in three dimensions. We illustrate applications of the proposed modelling framework and numerical method by reporting on numerical simulations of a model for eukaryotic chemotaxis and a model for the persistent movement of keratocytes in two and three space dimensions. Movies of the simulated cells can be obtained from http://homepages.warwick.ac.uk/~maskae/CV_Warwick/Chemotaxis.html. PMID- 22675165 TI - Modelling the spread of Wolbachia in spatially heterogeneous environments. AB - The endosymbiont Wolbachia infects a large number of insect species and is capable of rapid spread when introduced into a novel host population. The bacteria spread by manipulating their hosts' reproduction, and their dynamics are influenced by the demographic structure of the host population and patterns of contact between individuals. Reaction-diffusion models of the spatial spread of Wolbachia provide a simple analytical description of their spatial dynamics but do not account for significant details of host population dynamics. We develop a metapopulation model describing the spatial dynamics of Wolbachia in an age structured host insect population regulated by juvenile density-dependent competition. The model produces similar dynamics to the reaction-diffusion model in the limiting case where the host's habitat quality is spatially homogeneous and Wolbachia has a small effect on host fitness. When habitat quality varies spatially, Wolbachia spread is usually much slower, and the conditions necessary for local invasion are strongly affected by immigration of insects from surrounding regions. Spread is most difficult when variation in habitat quality is spatially correlated. The results show that spatial variation in the density dependent competition experienced by juvenile host insects can strongly affect the spread of Wolbachia infections, which is important to the use of Wolbachia to control insect vectors of human disease and other pests. PMID- 22675166 TI - The prognostic significance of vasohibin-1 expression in patients with upper urinary tract urothelial carcinoma. AB - PURPOSE: Vasohibin-1 (VASH1) is a novel angiogenic molecule that is specifically expressed in activated vascular endothelial cells, and the status of VASH1 expression has been documented in cancer angiogenesis. The aim of this study was to address the prognostic value of VASH1 expression in upper urinary tract urothelial carcinomas (UTUC). EXPERIMENTAL DESIGN: We retrospectively analyzed the clinical records of 171 patients with locally advanced UTUC (Ta-3N0M0). The median follow-up period was 3.8 years. We immunohistochemically examined the accomplished microvessels with anti-CD34 as microvessel density (MVD) and the microvessels with activated endothelial cells as VASH1 density. Then, we analyzed the association between immunohistochemical expression and clinical outcomes. RESULTS: Forty-two patients experienced tumor recurrence and of these 34 died of the disease during follow-up. VASH1 density was significantly associated with tumor grade, pathologic T stage, and MVD. The 5-year recurrence-free and cancer specific survival rates were 66.1% and 72.8% in patients with VASH1 density (>= 40/mm(2)) and 81.0% and 86.5% in their counterparts, respectively (P < 0.05). MVD was not an independent predictor of tumor recurrence or cancer-specific survival. Multivariate analyses revealed that high VASH1 density was an independent prognostic indicator of both tumor recurrence (P = 0.024, HR = 2.10) and cancer specific survival (P = 0.031, HR = 2.23) as well as other standard prognostic factors including high tumor grade and lymphovascular invasion. CONCLUSIONS: VASH1 density represents a clinically relevant predictor of patient prognosis in UTUC. The results suggest that VASH1 density could become a new biomarker and provide additional prognostic information in patients with UTUC. PMID- 22675167 TI - Functional analysis of the ATM-p53-p21 pathway in the LRF CLL4 trial: blockade at the level of p21 is associated with short response duration. AB - PURPOSE: This study sought to establish whether functional analysis of the ATM p53-p21 pathway adds to the information provided by currently available prognostic factors in patients with chronic lymphocytic leukemia (CLL) requiring frontline chemotherapy. EXPERIMENTAL DESIGN: Cryopreserved blood mononuclear cells from 278 patients entering the LRF CLL4 trial comparing chlorambucil, fludarabine, and fludarabine plus cyclophosphamide were analyzed for ATM-p53-p21 pathway defects using an ex vivo functional assay that uses ionizing radiation to activate ATM and flow cytometry to measure upregulation of p53 and p21 proteins. Clinical endpoints were compared between groups of patients defined by their pathway status. RESULTS: ATM-p53-p21 pathway defects of four different types (A, B, C, and D) were identified in 194 of 278 (70%) samples. The type A defect (high constitutive p53 expression combined with impaired p21 upregulation) and the type C defect (impaired p21 upregulation despite an intact p53 response) were each associated with short progression-free survival. The type A defect was associated with chemoresistance, whereas the type C defect was associated with early relapse. As expected, the type A defect was strongly associated with TP53 deletion/mutation. In contrast, the type C defect was not associated with any of the other prognostic factors examined, including TP53/ATM deletion, TP53 mutation, and IGHV mutational status. Detection of the type C defect added to the prognostic information provided by TP53/ATM deletion, TP53 mutation, and IGHV status. CONCLUSION: Our findings implicate blockade of the ATM-p53-p21 pathway at the level of p21 as a hitherto unrecognized determinant of early disease recurrence following successful cytoreduction. PMID- 22675168 TI - Performance of p16/Ki-67 immunostaining to detect cervical cancer precursors in a colposcopy referral population. AB - PURPOSE: Cytology-based screening has limited sensitivity to detect prevalent cervical precancers. Human papilloma virus (HPV) DNA testing is highly sensitive and provides a high, long-term reassurance of low risk of cervical cancer. However, the specificity of HPV DNA testing is limited, requiring additional, more disease-specific markers for efficient screening approaches. EXPERIMENTAL DESIGN: Liquid-based cytology samples were collected from 625 women referred to colposcopy. A slide was stained using the CINtec plus cytology assay. Pap cytology and HPV genotyping were conducted from the same vial. Clinical performance characteristics were calculated for all women, stratified by age, and for women referred with a low-grade squamous intraepithelial lesion (LSIL) Pap. RESULTS: p16/Ki-67 positivity increased with histologic severity, from 26.8% in normal histology, 46.5% in CIN1, 82.8% in CIN2 to 92.8% in CIN3. Among women with CIN3, p16/Ki-67 positivity increased from 77.8% for women younger than 30 years without HPV16 to 100% for women 30 years and older with HPV16. The sensitivity and specificity to detect CIN3+ were 93.2% and 46.1%, respectively, and increased to 97.2% and 60.0% among women 30 years and older. In women with high-risk (HR) HPV-positive atypical squamous cells of undetermined significance (ASC-US) and LSIL, sensitivity and specificity for detection of CIN3 were 90.6% and 48.6%, respectively. CONCLUSIONS: p16/Ki-67 testing could reduce referral to colposcopy by almost half while detecting the most severe cases of CIN3. The high sensitivity of p16/Ki-67 with significantly improved specificity compared with HPV testing makes p16/Ki-67 a viable option for LSIL triage. Further studies are required to evaluate p16/Ki-67 as triage marker in HPV-based screening strategies. PMID- 22675169 TI - Overexpression of GOLPH3 promotes proliferation and tumorigenicity in breast cancer via suppression of the FOXO1 transcription factor. AB - PURPOSE: Golgi phosphoprotein 3 (GOLPH3) has been reported to be involved in various biologic processes. The clinical significance and biologic role of GOLPH3 in breast cancer, however, remains unknown. EXPERIMENTAL DESIGN: Expression of GOLPH3 in normal breast cells, breast cancer cells, and 6-paired breast cancer and adjacent noncancerous tissues were quantified using real-time PCR and Western blotting. GOLPH3 protein expression was analyzed in 258 archived, paraffin embedded breast cancer samples using immunohistochemistry. The role of GOLPH3 in breast cancer cell proliferation and tumorigenicity was explored in vitro and in vivo. Western blotting and luciferase reporter analyses were used to investigate the effect of GOLPH3 overexpression and silencing on the expression of cell-cycle regulators and FOXO1 transcriptional activity. RESULTS: GOLPH3 was significantly upregulated in breast cancer cells and tissues compared with normal cells and tissues. Immunohistochemical analysis revealed high expression of GOLPH3 in 133 of 258 (51.6%) breast cancer specimens. Statistical analysis showed a significant correlation of GOLPH3 expression with advanced clinical stage and poorer survival. Overexpression and ablation of GOLPH3 promoted and inhibited, respectively, the proliferation and tumorigenicity of breast cancer cells in vitro and in vivo. GOLPH3 overexpression enhanced AKT activity and decreased FOXO1 transcriptional activity, downregulated cyclin-dependent kinase (CDK) inhibitor p21(Cip1), p27(Kip1), and p57(Kip2), and upregulated the CDK regulator cyclin D1. CONCLUSION: Our results suggest that high GOLPH3 expression is associated with poor overall survival in patients with breast cancer and that GOLPH3 overexpression increases the proliferation and tumorigenicity of human breast cancer cells. PMID- 22675170 TI - TP53 genomic status regulates sensitivity of gastric cancer cells to the histone methylation inhibitor 3-deazaneplanocin A (DZNep). AB - PURPOSE: DZNep (3-deazaneplanocin A) depletes EZH2, a critical component of polycomb repressive complex 2 (PRC2), which is frequently deregulated in cancer. Despite exhibiting promising anticancer activity, the specific genetic determinants underlying DZNep responsiveness in cancer cells remain largely unknown. We sought to determine molecular factors influencing DZNep response in gastric cancer. EXPERIMENTAL DESIGN: Phenotypic effects of DZNep were evaluated in a panel of gastric cancer cell lines. Sensitive lines were molecularly interrogated to identify potential predictors of DZNep responsiveness. The functional importance of candidate predictors was evaluated using short hairpin RNA (shRNA) and siRNA technologies. RESULTS: DZNep depleted PRC2 pathway components in almost all gastric cancer lines, however, only a subset of lines exhibited growth inhibition upon treatment. TP53 genomic status was significantly associated with DZNep cellular responsiveness, with TP53 wild-type (WT) lines being more sensitive (P < 0.001). In TP53-WT lines, DZNep stabilized p53 by reducing ubiquitin conjugation through USP10 upregulation, resulting in activation of canonical p53 target genes. TP53 knockdown in TP53-WT lines attenuated DZNep sensitivity and p53 target activation, showing the functional importance of an intact p53 pathway in regulating DZNep cellular sensitivity. In primary human gastric cancers, EZH2 expression was negatively correlated with p53 pathway activation, suggesting that higher levels of EZH2 may repress p53 activity. CONCLUSION: Our results highlight an important role for TP53 genomic status in influencing DZNep response in gastric cancer. Clinical trials evaluating EZH2-targeting agents such as DZNep should consider stratifying patients with gastric cancer by their TP53 genomic status. PMID- 22675171 TI - Progenitor-like traits contribute to patient survival and prognosis in oligodendroglial tumors. AB - PURPOSE: Patient-derived glioma-propagating cells (GPC) contain karyotypic and gene expression profiles that are found in the primary tumor. However, their clinical relevance is unclear. We ask whether GPCs contribute to disease progression and survival outcome in patients with glioma by analyzing gene expression profiles. EXPERIMENTAL DESIGN: We tapped into public sources of GPC gene expression data and derived a gene signature distinguishing oligodendroglial from glioblastoma multiforme (GBM) GPCs. By adapting a method in glioma biology, the Connectivity Map, we interrogated its strength of association in public clinical databases. We validated the top-ranking signaling pathways Wnt, Notch, and TGFbeta, in GPCs and primary tumor specimens. RESULTS: We observed that patients with better prognosis correlated with oligodendroglial GPC features and lower tumor grade, and this was independent of the current clinical indicator, 1p/19q status. Patients with better prognosis had proneural tumors whereas the poorly surviving cohort had mesenchymal tumors. In addition, oligodendroglial GPCs were more sensitive to Wnt and Notch inhibition whereas GBM GPCs responded to TGFbetaR1 inhibition. CONCLUSIONS: We provide evidence that GPCs are clinically relevant. In addition, the more favorable prognosis of oligodendroglial tumors over GBM could be recapitulated transcriptomically at the GPC level, underscoring the relevance of this cellular model. Our gene signature detects molecular heterogeneity in oligodendroglial tumors that cannot be accounted for by the 1p/19q status alone, indicating that stem-like traits contribute to clinical status. Collectively, these data highlight the limitation of morphology-based histologic analyses in tumor classification, consequently impacting on treatment decisions. PMID- 22675172 TI - Inhibition of histone deacetylation potentiates the evolution of acquired temozolomide resistance linked to MGMT upregulation in glioblastoma xenografts. AB - PURPOSE: The therapeutic benefit of temozolomide in glioblastoma multiforme (GBM) is limited by resistance. The goal of this study was to elucidate mechanisms of temozolomide resistance in GBM. EXPERIMENTAL DESIGN: We developed an in vivo GBM model of temozolomide resistance and used paired parental and temozolomide resistant tumors to define the mechanisms underlying the development of resistance and the influence of histone deacetylation (HDAC) inhibition. RESULTS: Analysis of paired parental and resistant lines showed upregulation of O6 methylguanine-DNA methyltransferase (MGMT) expression in 3 of the 5 resistant xenografts. While no significant change was detected in MGMT promoter methylation between parental and derivative-resistant samples, chromatin immunoprecipitation showed an association between MGMT upregulation and elevated acetylation of lysine 9 of histone H3 (H3K9-ac) and decreased dimethylation (H3K9-me2) in GBM12 and GBM14. In contrast, temozolomide resistance development in GBM22 was not linked to MGMT expression, and both parental and resistant lines had low H3K9-ac and high H3K9-me2 within the MGMT promoter. In the GBM12TMZ-resistant line, MGMT reexpression was accompanied by increased recruitment of SP1, C-JUN, NF-kappaB, and p300 within the MGMT promoter. Interestingly, combined treatment of GBM12 flank xenografts with temozolomide and the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) favored the evolution of temozolomide resistance by MGMT overexpression as compared with treatment with temozolomide alone. CONCLUSION: This study shows, for the first time, a unique mechanism of temozolomide resistance development driven by chromatin-mediated MGMT upregulation and highlights the potential for epigenetically directed therapies to influence the mechanisms of resistance development in GBM. PMID- 22675173 TI - Pretreatment EBV-DNA copy number is predictive of response and toxicities to SMILE chemotherapy for extranodal NK/T-cell lymphoma, nasal type. AB - PURPOSE: Extranodal NK/T-cell lymphoma, nasal type (ENKL) is an Epstein-Barr virus (EBV)-associated lymphoma for which a new chemotherapeutic regimen called SMILE (steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide) recently showed promising results. EXPERIMENTAL DESIGN: The amount of EBV-DNA was prospectively measured in whole-blood and plasma samples by real-time quantitative PCR from 26 patients registered in the SMILE phase II study. RESULTS: Before treatment, the EBV-DNA was detected in 22 samples of whole blood with a median number of 3,691 copies/mL (range: 0-1.14 * 10(7)), but 15 samples of plasma with a median of 867 copies/mL (range: 0-1.27 * 10(7)). Results of these 2 measurements of EBV-DNA well correlated (R(2) = 0.994, P < 0.001). The overall response rate to SMILE was significantly higher in patients with less than 10(5) copies/mL of EBV-DNA in whole blood at enrollment (90% vs. 20%, P = 0.007) and in patients with less than 10(4) copies/mL of EBV-DNA in plasma (95% vs. 29%, P = 0.002). The incidence of grade 4 toxicity of SMILE other than leukopenia/neutropenia was significantly higher in patients with 10(5) copies/mL of EBV-DNA or more in whole blood (100% vs. 29%, P = 0.007) than that of others and in patients with 10(4) copies/mL or more in plasma (86% vs. 26%, P = 0.002). CONCLUSIONS: These findings suggest that whole blood is more sensitive for clinical use than plasma. The EBV-DNA amount in whole blood was useful for predicting tumor response, toxicity, and prognosis after SMILE chemotherapy for ENKL. PMID- 22675175 TI - Cure models as a useful statistical tool for analyzing survival. AB - Cure models are a popular topic within statistical literature but are not as widely known in the clinical literature. Many patients with cancer can be long term survivors of their disease, and cure models can be a useful tool to analyze and describe cancer survival data. The goal of this article is to review what a cure model is, explain when cure models can be used, and use cure models to describe multiple myeloma survival trends. Multiple myeloma is generally considered an incurable disease, and this article shows that by using cure models, rather than the standard Cox proportional hazards model, we can evaluate whether there is evidence that therapies at the University of Arkansas for Medical Sciences induce a proportion of patients to be long-term survivors. PMID- 22675174 TI - Molecular profiling reveals low- and high-grade forms of primary melanoma. AB - PURPOSE: For primary melanomas, tumor thickness, mitotic rate, and ulceration are well-laid cornerstones of prognostication. However, a molecular exposition of melanoma aggressiveness is critically missing. We recently uncovered a four-class structure in metastatic melanoma, which predicts outcome and informs biology. This raises the possibility that a molecular structure exists even in the early stages of melanoma and that molecular determinants could underlie histophenotype and eventual patient outcome. EXPERIMENTAL DESIGN: We subjected 223 archival primary melanomas to a horizontally integrated analysis of RNA expression, oncogenic mutations at 238 lesions, histomorphometry, and survival data. RESULTS: Our previously described four-class structure that was elucidated in metastatic lesions was evident within the expression space of primary melanomas. Because these subclasses converged into two larger prognostic and phenotypic groups, we used the metastatic lesions to develop a binary subtype-based signature capable of distinguishing between "high" and "low" grade forms of the disease. The two grade signature was subsequently applied to the primary melanomas. Compared with low-grade tumors, high-grade primary melanomas were significantly associated with increased tumor thickness, mitotic rate, ulceration (all P < 0.01), and poorer relapse-free (HR = 4.94; 95% CI, 2.84-8.59), and overall (HR = 3.66; 95% CI, 2.40 5.58) survival. High-grade melanomas exhibited elevated levels of proliferation and BRCA1/DNA damage signaling genes, whereas low-grade lesions harbored higher expression of immune genes. Importantly, the molecular-grade signature was validated in two external gene expression data sets. CONCLUSIONS: We provide evidence for a molecular organization within melanomas, which is preserved across all stages of disease. PMID- 22675176 TI - Smelling, feeling, tasting and touching: behavioral and neural integration of antennular chemosensory and mechanosensory inputs in the crayfish. AB - Crustaceans possess two pairs of prominent, movable sense organs on the rostral aspect of their bodies termed antennae: (1) a relatively short, usually bifurcate pair, the 1st antennae, also referred to as antennules, and (2) a much longer, uniramous pair, the 2nd antennae, or just 'antennae'. The antennules are equipped with diverse arrays of six or more types of cuticular setae, most of which are believed to have a sensory function. Axons from these structures course within the antennular nerve to the deutocerebrum, a large middle brain region that is known to receive chemoreceptor and mechanoreceptor inputs. In crayfish, axons from two kinds of single sensory-function setae, the olfactory receptor aesthetasc sensilla and as yet unidentified hydrodynamic sensilla, on the lateral antennular flagellum terminate, respectively, within the ipsilateral olfactory lobe and the lateral antennular neuropil of the deutocerebrum, where their activity generates synaptic potentials in local interneurons having dendritic fields that span both of those regions. It has been suggested that the short latency hydrodynamic input gates or otherwise supplements the olfactory input signals. Much less is known about the functional capabilities of the other sensillar types on the antennular flagella, including the bimodal sensilla: how their inputs are distributed to the various neuropils of the deutocerebrum, whether they target common or separate brain neurons, and the nature, if any, of their functional relationships to the aesthetasc and hydrodynamic sensilla. Integrated processing of chemical and hydrodynamic signals undoubtedly plays an important role in locating odorant sources, perhaps by detecting boundaries of odorant plumes (tropotactic discrimination); other less-plausible strategies include time averaging of turbulent odorant signals and determination of concentration slopes within turbulence-generated odorant patches. These gaps in our understanding present important, but surmountable, experimental challenges for the future. PMID- 22675177 TI - Illumination preference, illumination constancy and colour discrimination by bumblebees in an environment with patchy light. AB - Patchy illumination presents foraging animals with a challenge, as the targets being sought may appear to vary in colour depending on the illumination, compromising target identification. We sought to explore how the bumblebee Bombus terrestris copes with tasks involving flower colour discrimination under patchy illumination. Light patches varied between unobscured daylight and leaf-shade, as a bee might encounter in and around woodland. Using a flight arena and coloured filters, as well as one or two different colours of artificial flower, we quantified how bees chose to forage when presented with foraging tasks under patchy illumination. Bees were better at discriminating a pair of similar colours under simulated unobscured daylight illumination than when foraging under leaf shade illumination. Accordingly, we found that bees with prior experience of simulated daylight but not leaf-shade illumination initially preferred to forage in simulated daylight when all artificial flowers contained rewards as well as when only one colour was rewarding, whereas bees with prior experience of both illuminants did not exhibit this preference. Bees also switched between illuminants less than expected by chance. This means that bees prefer illumination conditions with which they are familiar, and in which rewarding flower colours are easily distinguishable from unrewarding ones. Under patchy illumination, colour discrimination performance was substantially poorer than in homogenous light. The bees' abilities at coping with patchy light may therefore impact on foraging behaviour in the wild, particularly in woodlands, where illumination can change over short spatial scales. PMID- 22675178 TI - Divergence of desiccation-related traits in two Drosophila species of the takahashii subgroup from the western Himalayas. AB - Drosophila nepalensis is more abundant under colder and drier montane habitats in the western Himalayas compared with Drosophila takahashii, but the mechanistic basis of such a climatic adaptation is largely unknown. We tested the hypothesis that divergence in the physiological basis of desiccation-related traits is consistent with species-specific adaptations to climatic conditions. Drosophila nepalensis showed approximately twofold higher desiccation resistance, hemolymph content as well as carbohydrate content than D. takahashii despite a modest difference in rate of water loss (0.3% h(-1)). Water loss before succumbing to death (dehydration tolerance) was much higher in D. nepalensis (82.32%) than in D. takahashii (~50%). A greater loss of hemolymph water under desiccation stress until death is associated with higher desiccation resistance in D. nepalensis. In both species, carbohydrates were utilized under desiccation stress, but a higher level of stored carbohydrates was evident in D. nepalensis. Further, we found increased desiccation resistance in D. nepalensis through acclimation whereas D. takahashii lacked such a response. Thus, species-specific divergence in water balance-related traits in these species is consistent with their adaptations to wet and dry habitats. PMID- 22675179 TI - Further insight into the sound-producing mechanism of clownfishes: what structure is involved in sound radiation? AB - It was recently demonstrated that clownfishes produce aggressive sounds by snapping their jaw teeth. To date, only the onset of the sound has been studied, which raises the question, what structure is involved in sound radiation? Here, a combination of different approaches has been used to determine the anatomical structure(s) responsible for the size-related variations observed in sound duration and frequency. Filling the swimbladder with physiological liquid specifically modified size-related acoustic features by inducing a significant decrease in pulse duration of approximately 3 ms and a significant increase in dominant frequency of approximately 105 Hz. However, testing the acoustics of the swimbladder by striking it with a piezoelectric impact hammer showed that this structure is a highly damped sound source prevented from prolonged vibrations. In contrast, the resonant properties of the rib cage seems to account for the size related variations observed in acoustic features. For an equivalent strike on the rib cage, the duration and dominant frequency of induced sounds changed with fish size: sound duration and dominant frequency were positively and negatively correlated with fish size, respectively. Such relationships between sonic features and fish size are consistent with those observed in natural sounds emitted by fish. Therefore, the swimbladder itself does not act as a resonator; its wall just seems to be driven by the oscillations of the rib cage. This set of observations suggests the need for reassessment of the acoustic role of swimbladders in various fish species. PMID- 22675180 TI - Pheromone mediated modulation of pre-flight warm-up behavior in male moths. AB - An essential part of sexual reproduction typically involves the identification of an appropriate mating partner. Males of many moth species utilize the scent of sex pheromones to track and locate conspecific females. However, before males engage in flight, warm-up by shivering of the major flight muscles is necessary to reach a thoracic temperature suitable to sustain flight. Here we show that Helicoverpa zea males exposed to an attractive pheromone blend (and in some instances to the primary pheromone component alone) started shivering earlier and took off at a lower thoracic temperature than moths subjected to other incomplete or unattractive blends. This resulted in less time spent shivering and faster heating rates. Two interesting results emerge from these experiments. First, the rate of heat generation can be modulated by different olfactory cues. Second, males detecting the pheromone blend take off at lower thoracic temperatures than males exposed to other stimuli. The take-off temperature of these males was below that for optimal power production in the flight muscles, thus generating a trade off between rapid departure and suboptimal flight performance. Our results shed light on thermoregulatory behaviour of unrestrained moths associated with the scramble competition for access to females and suggest ecological trade-offs between rapid flight initiation and sub-optimal flight performance. PMID- 22675181 TI - Recognition of variable courtship song in the field cricket Gryllus assimilis. AB - We analyzed the courtship song of the field cricket Gryllus assimilis. The song comprises two elements: groups of ca. 10 pulses (chirps) with low fundamental frequency (3.5-3.7 kHz) alternating with high-frequency (15-17 kHz) pulses (ticks) that usually occur as doublets. Some elements of courtship song are quite variable (high coefficient of variation) both within and between males, whereas others are more stereotypical. In experiments with playback of synthesized courtship songs, we studied the importance of several song parameters for mating success, which we evaluated as the probability with which females mounted muted, courting males. Altering some features that show little variability, such as chirp-pulse rate or carrier frequency of ticks, resulted in significant decreases in mounting frequency, consistent with the notion that trait values showing little variability are constrained by stabilizing selection exerted by females. However, alteration of one invariant trait, the occurrence of both song components, by omitting either component from test songs only slightly affected female responsiveness. Alteration of a variable song trait, the number of ticks per song phrase, had no effect on female response rate, thus failing to provide support for the idea that variable traits provide a substrate for sexual selection. An unusual characteristic feature of the song of G. assimilis is that chirp pulses often contain substantial high-frequency power, and indeed may entirely lack power at the fundamental frequency. Playback experiments showed that such songs are, nevertheless, behaviorally effective. To understand the neural basis for this, we recorded the responses of the two principal ascending auditory interneurons of crickets, AN1 and AN2. Our results suggest that the frequency selectivity of the neurons is sufficiently broad to tolerate the spectral variability of courtship chirps. PMID- 22675182 TI - Survival of heat stress with and without heat hardening in Drosophila melanogaster: interactions with larval density. AB - Survival of a potentially lethal high temperature stress is a genetically variable thermal adaptation trait in many organisms. Organisms cope with heat stress by basal or induced thermoresistance. Here, we tested quantitative trait loci (QTL) for heat stress survival (HSS) in Drosophila melanogaster, with and without a cyclic heat-hardening pre-treatment, for flies that were reared at low (LD) or high (HD) density. Mapping populations were two panels of recombinant inbred lines (RIL), which were previously constructed from heat stress-selected stocks: RIL-D48 and RIL-SH2, derived from backcrosses to stocks of low and high heat resistance, respectively. HSS increased with heat hardening in both LD and HD flies. In addition, HSS increased consistently with density in non-hardened flies. There was a significant interaction between heat hardening and density effects in RIL-D48. Several QTL were significant for both density and hardening treatments. Many QTL overlapped with thermotolerance QTL identified for other traits in previous studies based on LD cultures only. However, three new QTL were found in HD only (cytological ranges: 12E-16F6; 30A3-34C2; 49C-50C). Previously found thermotolerance QTL were also significant for flies from HD cultures. PMID- 22675183 TI - Coordination of bat sonar activity and flight for the exploration of three dimensional objects. AB - The unique combination of flight and echolocation has opened the nocturnal air space as a rich ecological niche for bats. By analysing echoes of their sonar emissions, bats discriminate and recognize three-dimensional (3-D) objects. However, in contrast to vision, the 3-D information that can be gained by ensonifying an object from only one observation angle is sparse. To date, it is unclear how bats synchronize echolocation and flight activity to explore the 3-D shape of ensonified objects. We have devised an experimental design that allows creating 3-D virtual echo-acoustic objects by generating in real-time echoes from the bat's emissions that depend on the bat's position relative to the virtual object. Bats were trained to evaluate these 3-D virtual objects differing in their azimuthal variation of either echo amplitude or spectral composition. The data show that through a very effective coordination of sonar and flight activity, bats analyse an azimuthal variation of echo amplitude with a resolution of approximately 16 dB and a variation of echo centre frequency of approximately 19%. Control experiments show that the bats can detect not only these variations but also perturbations in the spatial arrangement of these variations. The current experimental paradigm shows that echolocating bats assemble echo-acoustic object information - acquired sequentially in flight - to reconstruct the 3-D shape of the ensonified object. Unlike previous approaches, the recruitment of virtual objects allows for a direct quantification of this reconstruction success in a highly controlled experimental approach. PMID- 22675184 TI - Flexibility in thermoregulatory physiology of two dunnarts, Sminthopsis macroura and Sminthopsis ooldea (Marsupialia; Dasyuridae). AB - Stripe-faced dunnarts (Sminthopsis macroura) and Ooldea dunnarts (S. ooldea) were acclimated for 2 weeks to ambient temperature (T(a)) regimes of 12-22 degrees C, 18-28 degrees C and 25-35 degrees C, and then measured for standard, basal (BMR) and maximum (MMR) metabolic rate using flow-through respirometry. Sminthopsis macroura maintained a stable body temperature under all experimental T(a) and acclimation regimes. Although its BMR was not statistically different between the three acclimation regimes, the lower end of the thermoneutral zone (TNZ) shifted from 30 degrees C under the 18-28 degrees C and 12-22 degrees C acclimation regimes to 35 degrees C under the 25-35 degrees C acclimation regime. MMR increased significantly at the cooler acclimation regimes. EWL increased at T(a)=35 degrees C, compared with lower T(a), in all acclimation regimes, but an increase in evaporative water loss (EWL) at T(a)=10 degrees C observed in cool acclimations did not occur at the 25-35 degrees C regime. In contrast, S. ooldea had variable body temperature between experimental T(a) in all acclimation regimes, but no acclimational shift in TNZ, which was between 30 and 35 degrees C. Neither BMR nor MMR was affected by exposure to the three acclimation regimes. EWL did not change across T(a) or with acclimation regime. Sminthopsis macroura was flexible in many aspects of its thermoregulation (involving energy and water balance) in response to thermal acclimation, presumably allowing it to balance its energy and water requirements over a broad range of climatic conditions. Sminthopsis ooldea seems to have an inflexible energetic and water balance in response to thermal acclimation, but has low nominal expenditure of either resource on thermoregulation because it thermoregulates less precisely than S. macroura. It seems that S. ooldea is adapted to a more narrow, stable climate. PMID- 22675185 TI - Thicker host tissues moderate light stress in a cnidarian endosymbiont. AB - The susceptibility of algal-cnidarian holobionts to environmental stress is dependent on attributes of both host and symbiont, but the role of the host is often unclear. We examined the influence of the host on symbiont light stress, comparing the photophysiology of the chlorophyte symbiont Elliptochloris marina in two species of sea anemones in the genus Anthopleura. After 3 months of acclimation in outdoor tanks, polyp photoprotective contraction behavior was similar between the two host species, but photochemical efficiency was 1.5 times higher in A. xanthogrammica than in A. elegantissima. Maximum relative electron transport rates, derived from rapid light curves, were 1.5 times higher in A. xanthogrammica than in A. elegantissima when symbionts were inside intact tissues, but were not significantly different between host species upon removal of outer (epidermis and mesoglea) tissue layers from symbiont-containing gastrodermal cells. Tissues of A. xanthogrammica were 1.8 times thicker than those of A. elegantissima, with outer tissue layers attenuating 1.6 times more light. We found no significant differences in light absorption properties per unit volume of tissue, confirming the direct effect of tissue thickness on light attenuation. The thicker tissues of A. xanthogrammica thus provide a favorable environment for E. marina - a relatively stress-susceptible symbiont - and may explain its higher prevalence and expanded range in A. xanthogrammica along the Pacific coast of North America. Our findings also support a photoprotective role for thicker host tissues in reef corals that has long been thought to influence variability in bleaching susceptibility among coral taxa. PMID- 22675186 TI - The discerning predator: decision rules underlying prey classification by a mosquito-eating jumping spider. AB - Evarcha culicivora is an East African jumping spider that feeds indirectly on vertebrate blood by choosing blood-fed female Anopheles mosquitoes as prey. Previous studies have shown that this predator can identify its preferred prey even when restricted to using only visual cues. Here, we used lures and virtual mosquitoes to investigate the optical cues underlying this predator's prey-choice behaviour. We made lures by dissecting and then reconstructing dead mosquitoes, combining the head plus thorax with different abdomens. Depending on the experiment, lures were either moving or motionless. Findings from the lure experiments suggested that, for E. culicivora, seeing a blood-fed female mosquito's abdomen on a lure was a necessary, but not sufficient, cue by which preferred prey was identified, as cues from the abdomen needed to be paired with cues from the head and thorax of a mosquito. Conversely, when abdomens were not visible or were identical, spiders based their decisions on the appearance of the head plus thorax of mosquitoes, choosing prey with female characteristics. Findings from a subsequent experiment using animated 3D virtual mosquitoes suggest that it is specifically the mosquito's antennae that influence E. culicivora's prey-choice decisions. Our results show that E. culicivora uses a complex process for prey classification. PMID- 22675187 TI - Flexibility in starting posture drives flexibility in kinematic behavior of the kinethmoid-mediated premaxillary protrusion mechanism in a cyprinid fish, Cyprinus carpio. AB - Premaxillary protrusion in cypriniform fishes involves rotation of the kinethmoid, an unpaired skeletal element in the dorsal midline of the rostrum. No muscles insert directly onto the kinethmoid, so its rotation must be caused by the movement of other bones. In turn, the kinethmoid is thought to push on the ascending processes of the premaxillae, effecting protrusion. To determine the causes and effects of kinethmoid motion, we used XROMM (x-ray reconstruction of moving morphology) to measure the kinematics of cranial bones in common carp, Cyprinus carpio. Mean kinethmoid rotation was 83 deg during premaxillary protrusion (18 events in 3 individuals). The kinethmoid rotates in a coordinated way with ventral translation of the maxillary bridge, and this ventral translation is likely driven primarily by the A1beta muscle. Analyses of flexibility (variability between behaviors) and coordination (correlation between bones within a behavior) indicate that motion of the maxillary bridge, not the lower jaw, drives premaxillary protrusion. Thus, upper jaw protrusion is decoupled from lower jaw depression, allowing for two separate modes of protrusion, open mouth and closed mouth. These behaviors serve different functions: to procure food and to sort food, respectively. Variation in starting posture of the maxilla alone dictates which type of protrusion is performed; downstream motions are invariant. For closed mouth protrusion, a ventrally displaced maxillary starting posture causes kinethmoid rotation to produce more ventrally directed premaxillary protrusion. This flexibility, bestowed by the kinethmoid-maxillary bridge-A1beta mechanism, one of several evolutionary novelties in the cypriniform feeding mechanism, may have contributed to the impressive trophic diversity that characterizes this speciose lineage. PMID- 22675188 TI - Differential effects of chronic hypoxia and feed restriction on the expression of leptin and its receptor, food intake regulation and the endocrine stress response in common carp. AB - Appetite suppression is a common response to hypoxia in fish that confers significant energy savings. Yet little is known about the endocrine signals involved in the regulation of food intake during chronic hypoxia. Thus, we assessed the impact of chronic hypoxia on food intake, the expression of the potent anorexigenic signal leptin and its receptor (lepr), the mRNA levels of key hypothalamic appetite-regulating genes, and the activity of the hypothalamic pituitary-interrenal (HPI) axis in common carp, Cyprinus carpio. Fish exposed to 10% O(2) saturation for 8 days were chronically anorexic and consumed on average 79% less food than normoxic controls. Hypoxia also elicited gradual and parallel increases in the expression of liver leptin-a-I, leptin-a-II, lepr and erythropoietin, a known hypoxia-responsive gene. In contrast, the liver mRNA levels of all four genes remained unchanged in normoxic fish pair-fed to the hypoxia treatment. In the hypothalamus, expression of the appetite-regulating genes were consistent with an inhibition and stimulation of hunger in the hypoxic and pair-fed fish, respectively, and reduced feed intake led to a decrease in lepr. Although both treatments elicited similar delayed increases in plasma cortisol, they were characterized by distinct HPI axis effector transcript levels and a marked differential increase in pituitary lepr expression. Together, these results show that a reduction in O(2) availability, and not feed intake, stimulates liver leptin-a expression in common carp and suggest that this pleiotropic cytokine is involved in the regulation of appetite and the endocrine stress response during chronic hypoxia. PMID- 22675189 TI - The role of elastic energy storage and recovery in downhill and uphill running. AB - In level running, humans and other animals store and recover elastic energy during each step. What role does elastic energy play during downhill and uphill running? We measured the fluctuations of the mechanical energy of the center of mass (CoM) of 15 human participants running at 3 m s(-1) on the level, downhill and uphill on a force-measuring treadmill mounted at 3, 6 and 9 deg. In level running, nearly symmetrical decreases and increases of the combined gravitational potential and kinetic (GPE+KE) energy of the CoM indicated equal possible elastic energy storage and recovery. However, asymmetrical fluctuations during hill running indicate reduced maximum possible elastic energy storage and return. We analyzed mechanical energy generation and dissipation during level and hill running by quantifying the anatomically estimated elastic energy storage (AEEE) in the arch and Achilles' tendon using peak ground reaction forces and anatomical characteristics. AEEE did not change with grade. At shallow downhill grades, the body must generate mechanical energy, though it dissipates more than it generates. At steeper downhill grades, little to no energy generation is required and only mechanical energy dissipation must occur. The downhill grade at which mechanical energy must no longer be generated occurs at approximately -9 deg, near the metabolically optimal running grade. At shallow uphill grades, mechanical energy must be generated to raise the CoM, and at steeper grades, additional energy must be generated to offset reduced elastic energy storage and return. PMID- 22675190 TI - How forelimb and hindlimb function changes with incline and perch diameter in the green anole, Anolis carolinensis. AB - The range of inclines and perch diameters in arboreal habitats poses a number of functional challenges for locomotion. To effectively overcome these challenges, arboreal lizards execute complex locomotor behaviors involving both the forelimbs and the hindlimbs. However, few studies have examined the role of forelimbs in lizard locomotion. To characterize how the forelimbs and hindlimbs differentially respond to changes in substrate diameter and incline, we obtained three dimensional high-speed video of green anoles (Anolis carolinensis) running on flat (9 cm wide) and narrow (1.3 cm) perches inclined at 0, 45 and 90 deg. Changes in perch diameter had a greater effect on kinematics than changes in incline, and proximal limb variables were primarily responsible for these kinematic changes. In addition, a number of joint angles exhibited greater excursions on the 45 deg incline compared with the other inclines. Anolis carolinensis adopted strategies to maintain stability similar to those of other arboreal vertebrates, increasing limb flexion, stride frequency and duty factor. However, the humerus and femur exhibited several opposite kinematic trends with changes in perch diameter. Further, the humerus exhibited a greater range of motion than the femur. A combination of anatomy and behavior resulted in differential kinematics between the forelimb and the hindlimb, and also a potential shift in the propulsive mechanism with changes in external demand. This suggests that a better understanding of single limb function comes from an assessment of both forelimbs and hindlimbs. Characterizing forelimb and hindlimb movements may reveal interesting functional differences between Anolis ecomorphs. Investigations into the physiological mechanisms underlying the functional differences between the forelimb and the hindlimb are needed to fully understand how arboreal animals move in complex habitats. PMID- 22675191 TI - Respiratory dynamics of discontinuous gas exchange in the tracheal system of the desert locust, Schistocerca gregaria. AB - Gas exchange dynamics in insects is of fundamental importance to understanding evolved variation in breathing patterns, such as discontinuous gas exchange cycles (DGCs). Most insects do not rely solely on diffusion for the exchange of respiratory gases but may also make use of respiratory movements (active ventilation) to supplement gas exchange at rest. However, their temporal dynamics have not been widely investigated. Here, intratracheal pressure, V(CO2) and body movements of the desert locust Schistocerca gregaria were measured simultaneously during the DGC and revealed several important aspects of gas exchange dynamics. First, S. gregaria employs two different ventilatory strategies, one involving dorso-ventral contractions and the other longitudinal telescoping movements. Second, although a true spiracular closed (C)-phase of the DGC could be identified by means of subatmospheric intratracheal pressure recordings, some CO(2) continued to be released. Third, strong pumping actions do not necessarily lead to CO(2) release and could be used to ensure mixing of gases in the closed tracheal system, or enhance water vapour reabsorption into the haemolymph from fluid-filled tracheole tips by increasing the hydrostatic pressure or forcing fluid into the haemocoel. Finally, this work showed that the C-phase of the DGC can occur at any pressure. These results provide further insights into the mechanistic basis of insect gas exchange. PMID- 22675193 TI - Differences in critical thermal maxima and mortality across life stages of the mealworm beetle Tenebrio molitor. AB - Thermal limits to activity profoundly affect the abundance and distribution of ectothermic animals. Upper thermal limits to activity are typically reported as the critical thermal maximum (CT(max)), the temperature at which activity becomes uncontrolled. Thermolimit respirometry is a new technique that allows CT(max) to be quantified in small animals, such as insects, as the point of spiracular failure by measuring CO(2) release from the animal as temperature increases. Although prior studies have reported a characteristic pattern of CO(2) release for insects during thermolimit respirometry trials, no studies have been carried out to determine the universality of this pattern across development, or at what point death occurs along this pattern. Here, we compared the CT(max) and patterns of CO(2) release among three life stages of a beetle species, Tenebrio molitor, and mapped heat death onto these patterns. Our study is the first to report distinct patterns of CO(2) release in different life stages of an insect species during thermolimit respirometry. Our results show that CT(max) was significantly higher in adult beetles than in either larvae or pupae (P<0.001) and, similarly, death occurred at higher temperatures in adults than in larvae and pupae. We also found that death during heating closely follows CT(max) in these animals, which confirms that measuring the loss of spiracular control with thermolimit respirometry successfully identifies the point of physiological limitation during heat stress. PMID- 22675192 TI - Inter-animal variability in the effects of C-type allatostatin on the cardiac neuromuscular system in the lobster Homarus americanus. AB - Although the global effects of many modulators on pattern generators are relatively consistent among preparations, modulators can induce different alterations in different preparations. We examined the mechanisms that underlie such variability in the modulatory effects of the peptide C-type allatostatin (C AST; pQIRYHQCYFNPISCF) on the cardiac neuromuscular system of the lobster Homarus americanus. Perfusion of C-AST through the semi-intact heart consistently decreased the frequency of ongoing contractions. However, the effect of C-AST on contraction amplitude varied between preparations, decreasing in some preparations and increasing in others. To investigate this variable effect, we examined the effects of C-AST both peripherally and centrally. When contractions of the myocardium were elicited by controlled stimuli, C-AST did not alter heart contraction at the periphery (myocardium or neuromuscular junction) in any hearts. However, when applied either to the semi-intact heart or to the cardiac ganglion (CG) isolated from hearts that responded to C-AST with increased contraction force, C-AST increased both motor neuron burst duration and the number of spikes per burst by about 25%. In contrast, CG output was increased only marginally in hearts that responded to C-AST with a decrease in contraction amplitude, suggesting that the decrease in amplitude in those preparations resulted from decreased peripheral facilitation. Our data suggest that the differential effects of a single peptide on the cardiac neuromuscular system are due solely to differential effects of the peptide on the pattern generator; the extent to which the peptide induces increased burst duration is crucial in determining its overall effect on the system. PMID- 22675194 TI - Development of cardiovascular function in the marine gastropod Littorina obtusata (Linnaeus). AB - The molluscan cardiovascular system typically incorporates a transient extracardiac structure, the larval heart, early in development, but the functional importance of this structure is unclear. We documented the ontogeny and regulatory ability of the larval heart in relation to two other circulatory structures, the true heart and the velum, in the intertidal gastropod Littorina obtusata. There was a mismatch between the appearance of the larval heart and the velum. Velar lobes appeared early in development (day 4), but the larval heart did not begin beating until day 13. The beating of the larval heart reached a maximum on day 17 and then decreased until the structure itself disappeared (day 24). The true heart began to beat on day 17. Its rate of beating increased as that of the larval heart decreased, possibly suggesting a gradual shift from a larval heart-driven to a true heart-driven circulation. The true heart was not sensitive to acutely declining P(O(2)) shortly after it began to beat, but increased in activity in response to acutely declining P(O(2)) by day 21. Larval heart responses were similar to those of the true heart, with early insensitivity to declining P(O(2)) (day 13) followed by a response by day 15. Increased velum driven rotational activity under acutely declining P(O(2)) was greatest in early developmental stages. Together, these findings point to cardiovascular function in L. obtusata larvae being the result of a complex interaction between velum, larval and true heart activities, with the functions of the three structures coinciding but their relative importance changing throughout larval development. PMID- 22675195 TI - Experience-dependent modulation of antennal sensitivity and input to antennal lobes in male moths (Spodoptera littoralis) pre-exposed to sex pheromone. AB - Sex pheromones are intraspecific olfactory signals emitted by one sex to attract a potential mating partner. Behavioural responses to sex pheromones are generally highly stereotyped. However, they can be modulated by experience, as male moths previously exposed to female sex pheromone respond with a lower threshold upon further detection, even after long delays. Here, we address the question of the neural mechanisms underlying such long-term modulation. As previous work has shown increased responses to pheromone in central olfactory neurons, we asked whether brief exposure to the pheromone increases input activity from olfactory receptor neurons. Males pre-exposed to sex pheromone exhibited increased peripheral sensitivity to the main pheromone component. Among nine antennal genes targeted as putatively involved in pheromone reception, one encoding a pheromone binding protein showed significant upregulation upon exposure. In the primary olfactory centre (antennal lobe), the neural compartment processing the main pheromone component was enlarged after a brief pheromone exposure, thus suggesting enduring structural changes. We hypothesise that higher peripheral sensitivity following pre-exposure leads to increased input to the antennal lobe, thus contributing to the structural and functional reorganization underlying a stable change in behaviour. PMID- 22675196 TI - Spectral sensitivity of phototaxis in the dinoflagellate Kryptoperidinium foliaceum and their reaction to physical encounters. AB - The dinoflagellate Kryptoperidinium foliaceum possesses one of the largest eyespots among the autotrophic dinoflagellates. Until now they were believed to be negatively phototactic using a non-opsin photopigment. Here we provide evidence that in newly established cultures they are positively phototactic and that the dynamic range of phototaxis is ~2.5 log units. Additionally, we find that the spectral sensitivity of the phototaxis agrees reasonably well with the absorption curve of a theoretical opsin, with a peak sensitivity around 500 nm. The sensitivity in the short wavelength end of the tested spectrum is unexpectedly low, but this is probably due to selective filtering. Interestingly, the phototaxis could be temporarily overruled by tactile stimuli. After physical contact with the light guide, the cells escaped the area, and we suggest that this may serve as predator avoidance. PMID- 22675197 TI - Thyroid function during pregnancy: who and how should we screen? PMID- 22675198 TI - Identification of follistatin-like 1 by expression cloning as an activator of the growth differentiation factor 15 gene and a prognostic biomarker in acute coronary syndrome. AB - BACKGROUND: Growth differentiation factor 15 (GDF15) is a stress-responsive cytokine and biomarker that is produced after myocardial infarction and that is related to prognosis in acute coronary syndrome (ACS). We hypothesized that secreted proteins that activate GDF15 production may represent new ACS biomarkers. METHODS: We expressed clones from an infarcted mouse heart cDNA library in COS1 cells and assayed for activation of a luciferase reporter gene controlled by a 642-bp fragment of the mouse growth differentiation factor 15 (GDF15) gene promoter. We measured the circulating concentrations of follistatin like 1 (FSTL1) and GDF15 in 1369 patients with ACS. RESULTS: One cDNA clone that activated the GDF15 promoter-luciferase reporter encoded the secreted protein FSTL1. Treatment with FSTL1 activated GDF15 production in cultured cardiomyocytes. Transgenic production of FSTL1 stimulated GDF15 production in the murine heart, whereas cardiomyocyte-selective deletion of FSTL1 decreased production of GDF15 in cardiomyocytes, indicating that FSTL1 is sufficient and required for GDF15 production. In ACS, FSTL1 emerged as the strongest independent correlate of GDF15 (partial R(2) = 0.26). A total of 106 patients died of a cardiovascular cause during a median follow-up of 252 days. Patients with an FSTL1 concentration in the top quartile had a 3.7-fold higher risk of cardiovascular death compared with patients in the first 3 quartiles (P < 0.001). FSTL1 remained associated with cardiovascular death after adjustment for clinical, angiographic, and biochemical variables. CONCLUSIONS: Our study is the first to use expression cloning for biomarker discovery upstream of a gene of interest and to identify FSTL1 as an independent prognostic biomarker in ACS. PMID- 22675199 TI - Mitochondrial transcription factor A serves as a danger signal by augmenting plasmacytoid dendritic cell responses to DNA. AB - Plasmacytoid dendritic cells (pDC) are potent APCs known to regulate immune responses to self-Ags, particularly DNA. The mitochondrial fraction of necrotic cells was found to most potently promote human pDC activation, as reflected by type I IFN release, which was dependent upon the presence of mitochondrial DNA and involved TLR9 and receptors for advanced glycation end products. Mitochondrial transcription factor A (TFAM), a highly abundant mitochondrial protein that is functionally and structurally homologous to high mobility group box protein 1, was observed to synergize with CpG-containing oligonucleotide, type A, DNA to promote human pDC activation. pDC type I IFN responses to TFAM and CpG-containing oligonucleotide, type A, DNA indicated their engagement with receptors for advanced glycation end products and TLR9, respectively, and were dependent upon endosomal processing and PI3K, ERK, and NF-kappaB signaling. Taken together, these results indicate that pDC contribute to sterile immune responses by recognizing the mitochondrial component of necrotic cells and further incriminate TFAM and mitochondrial DNA as likely mediators of pDC activation under these circumstances. PMID- 22675200 TI - Toso, a functional IgM receptor, is regulated by IL-2 in T and NK cells. AB - We find that the cell surface receptor Toso is dramatically downregulated by in vitro stimulation of human T and NK cells with IL-2 in a STAT5-dependent manner. The fact that IL-2 is known to prime NK and T cells for Fas/TNF-mediated activation-induced cell death (AICD) fits nicely with the original and recent descriptions of Toso as an inhibitor of Fas/TNF-induced apoptosis. In support of this possibility, effector memory T cells express markedly lower levels of Toso than those of naive T cells, indicating that activation in vivo correlates with the downregulation of Toso. Moreover, in vitro activation of memory T cells through TCR dramatically downregulates Toso expression compared with that of naive CD4 T cells. However, overexpression of Toso in human NK cells and Jurkat T cells does not inhibit Fas-mediated apoptosis, and, in agreement with other recent reports, Toso clearly functions as an IgM receptor. Unlike CD16, Toso expression by NK cells does not convey cytotoxic potential, but its ligation does trigger intracellular signaling in NK cells. In summary, our data indicate that Toso is a functional IgM receptor that is capable of activating signaling molecules, is regulated by IL-2, and is not inherently an antiapoptotic molecule. PMID- 22675201 TI - Autoreactive preplasma cells break tolerance in the absence of regulation by dendritic cells and macrophages. AB - The ability to induce Ab responses to pathogens while maintaining the quiescence of autoreactive cells is an important aspect of immune tolerance. During activation of TLR4, dendritic cells (DCs) and macrophages (MFs) repress autoantibody production through their secretion of IL-6 and soluble CD40L (sCD40L). These soluble mediators selectively repress B cells chronically exposed to Ag, but not naive cells, suggesting a means to maintain tolerance during TLR4 stimulation, yet allow immunity. In this study, we identify TNF-alpha as a third repressive factor, which together with IL-6 and CD40L account for nearly all the repression conferred by DCs and MFs. Similar to IL-6 and sCD40L, TNF-alpha did not alter B cell proliferation or survival. Instead, it reduced the number of Ab secreting cells. To address whether the soluble mediators secreted by DCs and MFs functioned in vivo, we generated mice lacking IL-6, CD40L, and TNF-alpha. Compared to wild-type mice, these mice showed prolonged anti-nuclear Ab responses following TLR4 stimulation. Furthermore, adoptive transfer of autoreactive B cells into chimeric IL-6(-/-) * CD40L(-/-) * TNF-alpha(-/-) mice showed that preplasma cells secreted autoantibodies independent of germinal center formation or extrafollicular foci. These data indicate that in the absence of genetic predisposition to autoimmunity, loss of endogenous IL-6, CD40L, and TNF-alpha promotes autoantibody secretion during TLR4 stimulation. PMID- 22675202 TI - IFN-gamma elicits macrophage autophagy via the p38 MAPK signaling pathway. AB - Autophagy is a major innate immune defense pathway in both plants and animals. In mammals, this cascade can be elicited by cytokines (IFN-gamma) or pattern recognition receptors (TLRs and nucleotide-binding oligomerization domain-like receptors). Many signaling components in TLR- and nucleotide-binding oligomerization domain-like receptor-induced autophagy are now known; however, those involved in activating autophagy via IFN-gamma remain to be elucidated. In this study, we engineered macrophages encoding a tandem fluorescently tagged LC3b (tfLC3) autophagosome reporter along with stably integrated short hairpin RNAs to demonstrate IFN-gamma-induced autophagy required JAK 1/2, PI3K, and p38 MAPK but not STAT1. Moreover, the autophagy-related guanosine triphosphatase Irgm1 proved dispensable in both stable tfLC3-expressing RAW 264.7 and tfLC3-transduced Irgm1( /-) primary macrophages, revealing a novel p38 MAPK-dependent, STAT1-independent autophagy pathway that bypasses Irgm1. These unexpected findings have implications for understanding how IFN-gamma-induced autophagy is mobilized within macrophages for inflammation and host defense. PMID- 22675203 TI - Recruitment of memory B cells to lymph nodes remote from the site of immunization requires an inflammatory stimulus. AB - Successful recall Ab responses require recruitment of quiescent memory B cells to secondary lymphoid organs. However, the cellular dynamics of memory cells responding to local antigenic challenge at lymphoid sites distal from the initial Ag encounter are not well understood. We show in this study that memory B cells generated following s.c. immunization in one footpad generate secondary responses to soluble Ag given i.p. but not to Ag given s.c. in the contralateral footpad unless LPS is coadministered. Memory B cells do not express CD62L, and CD62L(-ve) cells cannot enter lymph nodes unless LPS-mediated inflammation is induced there. Functional TLR4 is required on the B cells, as well as on non-B cells, in the lymph node to achieve full recruitment. Furthermore, splenectomized mice fail to respond to such inflammatory s.c. challenge in contralateral footpads, unlike lymphadenectomized mice lacking the original draining lymph nodes. Splenectomized mice also fail to respond to i.p. challenge with soluble Ag. Together, these data indicate that, unlike the central memory pool of T cells, which circulates through resting lymph nodes, the majority of long-lived memory B cells are spleen resident and require inflammatory signals for mounting recall responses at distal challenge sites. PMID- 22675205 TI - Origin of Drosophila mushroom body neuroblasts and generation of divergent embryonic lineages. AB - Key to understanding the mechanisms that underlie the specification of divergent cell types in the brain is knowledge about the neurectodermal origin and lineages of their stem cells. Here, we focus on the origin and embryonic development of the four neuroblasts (NBs) per hemisphere in Drosophila that give rise to the mushroom bodies (MBs), which are central brain structures essential for olfactory learning and memory. We show that these MBNBs originate from a single field of proneural gene expression within a specific mitotic domain of procephalic neuroectoderm, and that Notch signaling is not needed for their formation. Subsequently, each MBNB occupies a distinct position in the developing MB cortex and expresses a specific combination of transcription factors by which they are individually identifiable in the brain NB map. During embryonic development each MBNB generates an individual cell lineage comprising different numbers of neurons, including intrinsic gamma-neurons and various types of non-intrinsic neurons that do not contribute to the MB neuropil. This contrasts with the postembryonic phase of MBNB development during which they have been shown to produce identical populations of intrinsic neurons. We show that different neuron types are produced in a lineage-specific temporal order and that neuron numbers are regulated by differential mitotic activity of the MBNBs. Finally, we demonstrate that gamma-neuron axonal outgrowth and spatiotemporal innervation of the MB lobes follows a lineage-specific mode. The MBNBs are the first stem cells of the Drosophila CNS for which the origin and complete cell lineages have been determined. PMID- 22675204 TI - Polar opposites: Erk direction of CD4 T cell subsets. AB - Effective immune responses depend upon appropriate T cell differentiation in accord with the nature of an infectious agent, and the contingency of differentiation depends minimally on TCR, coreceptor, and cytokine signals. In this reverse genetic study, we show that the MAPK Erk2 is not essential for T cell proliferation in the presence of optimum costimulation. Instead, it has opposite effects on T-bet and Gata3 expression and, hence, on Th1 and Th2 differentiation. Alternatively, in the presence of TGF-beta, the Erk pathway suppresses a large program of gene expression, effectively limiting the differentiation of Foxp3(+) regulatory T cells. In the latter case, the mechanisms involved include suppression of Gata3 and Foxp3, induction of Tbx21, phosphorylation of Smad2,3, and possibly suppression of Socs2, a positive inducer of Stat5 signaling. Consequently, loss of Erk2 severely impeded Th1 differentiation while enhancing the development of Foxp3(+)-induced T regulatory cells. Selected profiles of gene expression under multiple conditions of T cell activation illustrate the opposing consequences of Erk pathway signaling. PMID- 22675206 TI - An E-cadherin-mediated hitchhiking mechanism for C. elegans germ cell internalization during gastrulation. AB - Gastrulation movements place endodermal precursors, mesodermal precursors and primordial germ cells (PGCs) into the interior of the embryo. Somatic cell gastrulation movements are regulated by transcription factors that also control cell fate, coupling cell identity and position. By contrast, PGCs in many species are transcriptionally quiescent, suggesting that they might use alternative gastrulation strategies. Here, we show that C. elegans PGCs internalize by attaching to internal endodermal cells, which undergo morphogenetic movements that pull the PGCs into the embryo. We show that PGCs enrich HMR-1/E-cadherin at their surfaces to stick to endoderm. HMR-1 expression in PGCs is necessary and sufficient to ensure internalization, suggesting that HMR-1 can promote PGC endoderm adhesion through a mechanism other than homotypic trans interactions between the two cell groups. Finally, we demonstrate that the hmr-1 3' untranslated region promotes increased HMR-1 translation in PGCs. Our findings reveal that quiescent PGCs employ a post-transcriptionally regulated hitchhiking mechanism to internalize during gastrulation, and demonstrate a morphogenetic role for the conserved association of PGCs with the endoderm. PMID- 22675207 TI - Evolutionarily conserved requirement of Cdx for post-occipital tissue emergence. AB - Mouse Cdx genes are involved in axial patterning and partial Cdx mutants exhibit posterior embryonic defects. We found that mouse embryos in which all three Cdx genes are inactivated fail to generate any axial tissue beyond the cephalic and occipital primordia. Anterior axial tissues are laid down and well patterned in Cdx null embryos, and a 3' Hox gene is initially transcribed and expressed in the hindbrain normally. Axial elongation stops abruptly at the post-occipital level in the absence of Cdx, as the posterior growth zone loses its progenitor activity. Exogenous Fgf8 rescues the posterior truncation of Cdx mutants, and the spectrum of defects of Cdx null embryos matches that resulting from loss of posterior Fgfr1 signaling. Our data argue for a main function of Cdx in enforcing trunk emergence beyond the Cdx-independent cephalo-occipital region, and for a downstream role of Fgfr1 signaling in this function. Cdx requirement for the post head section of the axis is ancestral as it takes place in arthropods as well. PMID- 22675208 TI - Foxp1/4 control epithelial cell fate during lung development and regeneration through regulation of anterior gradient 2. AB - The molecular pathways regulating cell lineage determination and regeneration in epithelial tissues are poorly understood. The secretory epithelium of the lung is required for production of mucus to help protect the lung against environmental insults, including pathogens and pollution, that can lead to debilitating diseases such as asthma and chronic obstructive pulmonary disease. We show that the transcription factors Foxp1 and Foxp4 act cooperatively to regulate lung secretory epithelial cell fate and regeneration by directly restricting the goblet cell lineage program. Loss of Foxp1/4 in the developing lung and in postnatal secretory epithelium leads to ectopic activation of the goblet cell fate program, in part, through de-repression of the protein disulfide isomerase anterior gradient 2 (Agr2). Forced expression of Agr2 is sufficient to promote the goblet cell fate in the developing airway epithelium. Finally, in a model of lung secretory cell injury and regeneration, we show that loss of Foxp1/4 leads to catastrophic loss of airway epithelial regeneration due to default differentiation of secretory cells into the goblet cell lineage. These data demonstrate the importance of Foxp1/4 in restricting cell fate choices during development and regeneration, thereby providing the proper balance of functional epithelial lineages in the lung. PMID- 22675209 TI - Regulated temporal-spatial astrocyte precursor cell proliferation involves BRAF signalling in mammalian spinal cord. AB - Expansion of astrocyte populations in the central nervous system is characteristic of evolutionarily more complex organisms. However, regulation of mammalian astrocyte precursor proliferation during development remains poorly understood. Here, we used Aldh1L1-GFP to identify two morphologically distinct types of proliferative astrocyte precursors: radial glia (RG) in the ventricular zone and a second cell type we call an 'intermediate astrocyte precursor' (IAP) located in the mantle region of the spinal cord. Astrogenic RG and IAP cells proliferated in a progressive ventral-to-dorsal fashion in a tight window from embryonic day 13.5 until postnatal day 3, which correlated precisely with the pattern of active ERK signalling. Conditional loss of BRAF function using BLBP cre resulted in a 20% decrease in astrocyte production, whereas expression of activated BRAFV600E resulted in astrocyte hyperproliferation. Interestingly, BRAFV600E mitogenic effects in astrocytes were restricted, in part, by the function of p16INK4A-p19(ARF), which limited the temporal epoch for proliferation. Together, these findings suggest that astrocyte precursor proliferation involves distinct RG and IAP cells; is subjected to temporal and spatial control; and depends in part on BRAF signalling at early stages of mammalian spinal cord development. PMID- 22675210 TI - Development-related PcG target in the apex 4 controls leaf margin architecture in Arabidopsis thaliana. AB - In a reverse genetics screen based on a group of genes enriched for development related Polycomb group targets in the apex (DPAs), we isolated DPA4 as a novel regulator of leaf margin shape. T-DNA insertion lines in the DPA4 locus display enhanced leaf margin serrations and enlarged petals, whereas overexpression of DPA4 results in smooth margins. DPA4 encodes a putative RAV (Related to ABI3/VP1) transcriptional repressor and is expressed in the lateral organ boundary region and in the sinus of leaf serrations. DPA4 expression domains overlap with those of the known leaf shape regulator CUP-SHAPED COTYLEDON 2 (CUC2) and we provide evidence that DPA4 negatively regulates CUC2 expression independently of MIR164A, an established regulator of CUC2. Taken together, the data suggest DPA4 as a newly identified player in the signalling network that controls leaf serrations in Arabidopsis thaliana. PMID- 22675212 TI - Wunen, a Drosophila lipid phosphate phosphatase, is required for septate junction mediated barrier function. AB - Lipid phosphate phosphatases (LPPs) are integral membrane enzymes that regulate the levels of bioactive lipids such as sphingosine 1-phosphate and lysophosphatidic acid. The Drosophila LPPs Wunen (Wun) and Wunen-2 (Wun2) have a well-established role in regulating the survival and migration of germ cells. We now show that wun has an essential tissue-autonomous role in development of the trachea: the catalytic activity of Wun is required to maintain septate junction (SJ) paracellular barrier function, loss of which causes failure to accumulate crucial luminal components, suggesting a role for phospholipids in SJ function. We find that the integrity of the blood-brain barrier is also lost in wun mutants, indicating that loss of SJ function is not restricted to the tracheal system. Furthermore, by comparing the rescue ability of different LPP homologs we show that wun function in the trachea is distinct from its role in germ cell migration. PMID- 22675211 TI - A Notch-dependent molecular circuitry initiates pancreatic endocrine and ductal cell differentiation. AB - In the pancreas, Notch signaling is thought to prevent cell differentiation, thereby maintaining progenitors in an undifferentiated state. Here, we show that Notch renders progenitors competent to differentiate into ductal and endocrine cells by inducing activators of cell differentiation. Notch signaling promotes the expression of Sox9, which cell-autonomously activates the pro-endocrine gene Ngn3. However, at high Notch activity endocrine differentiation is blocked, as Notch also induces expression of the Ngn3 repressor Hes1. At the transition from high to intermediate Notch activity, only Sox9, but not Hes1, is maintained, thus de-repressing Ngn3 and initiating endocrine differentiation. In the absence of Sox9 activity, endocrine and ductal cells fail to differentiate, resulting in polycystic ducts devoid of primary cilia. Although Sox9 is required for Ngn3 induction, endocrine differentiation necessitates subsequent Sox9 downregulation and evasion from Notch activity via cell-autonomous repression of Sox9 by Ngn3. If high Notch levels are maintained, endocrine progenitors retain Sox9 and undergo ductal fate conversion. Taken together, our findings establish a novel role for Notch in initiating both ductal and endocrine development and reveal that Notch does not function in an on-off mode, but that a gradient of Notch activity produces distinct cellular states during pancreas development. PMID- 22675213 TI - Transient downregulation of Bmp signalling induces extra limbs in vertebrates. AB - Bone morphogenetic protein (Bmp) signalling has been implicated in setting up dorsoventral patterning of the vertebrate limb and in its outgrowth. Here, we present evidence that Bmp signalling or, more precisely, its inhibition also plays a role in limb and fin bud initiation. Temporary inhibition of Bmp signalling either by overexpression of noggin or using a synthetic Bmp inhibitor is sufficient to induce extra limbs in the Xenopus tadpole or exogenous fins in the Danio rerio embryo, respectively. We further show that Bmp signalling acts in parallel with retinoic acid signalling, possibly by inhibiting the known limb inducing gene wnt2ba. PMID- 22675214 TI - Comment on "CD4+ CD8+ T cells represent a significant portion of the anti-HIV T cell response to acute HIV infection". PMID- 22675217 TI - Enthusiasm truly can be contagious! PMID- 22675215 TI - Hidden memories: frontline memory T cells and early pathogen interception. AB - Immunologic memory reflects the ability of a host to more effectively respond to a re-encounter with a particular pathogen than the first encounter, and when a vaccine mimics the first encounter, comprises the basis of vaccine efficacy. For T cells, memory is often equated with the anamnestic response, the ability of secondary lymphoid tissue-based (central) memory T cells to respond to pathogen exposure with a more rapid and higher magnitude production and infection-site delivery of pathogen-specific effector cells than observed in naive hosts. However, increasing evidence supports a fundamentally different kind of T cell memory in which differentiated, long-lived effector memory T cells, prepositioned in sites of potential pathogen invasion or rapidly mobilized to such sites from blood and marginated pools, intercept and potentially control/eliminate pathogen within hours of infection. In this article, we review the evidence for this "hidden" T cell memory and its implication for vaccine development. PMID- 22675218 TI - Why Canadian chiropractors need to support an increased research role. PMID- 22675220 TI - The JCCA is delighted to announce the recent appointment of Dr. Jeff Quon DC, PhD to Associate Editor. PMID- 22675216 TI - The rates of HIV superinfection and primary HIV incidence in a general population in Rakai, Uganda. AB - BACKGROUND: Human immunodeficiency virus (HIV) superinfection has been documented in high-risk individuals; however, the rate of superinfection among HIV-infected individuals within a general population remains unknown. METHODS: A novel next generation ultra-deep sequencing technique was utilized to determine the rate of HIV superinfection in a heterosexual population by examining two regions of the viral genome in longitudinal samples from recent HIV seroconverters (n=149) in Rakai District, Uganda. RESULTS: The rate of superinfection was 1.44 per 100 person years (PYs) (95% confidence interval [CI], .4-2.5) and consisted of both inter- and intrasubtype superinfections. This was compared to primary HIV incidence in 20 220 initially HIV-negative individuals in the general population in Rakai (1.15 per 100 PYs; 95% CI, 1.1-1.2; P= .26). Propensity score matching (PS) was used to control for differences in sociodemographic and behavioral characteristics between the HIV-positive individuals at risk for superinfection and the HIV-negative population at baseline and follow-up. After PS matching, the estimated rate of primary incidence was 3.28 per 100 PYs (95% CI, 2.0-5.3; P = .07) controlling for baseline differences and 2.51 per 100 PYs (95% CI, 1.5-4.3; P = .24) controlling for follow-up differences. CONCLUSIONS: This suggests that the rate of HIV superinfection in a general population is substantial, which could have a significant impact on future public health and HIV vaccine strategies. PMID- 22675219 TI - Developing a model curriculum for ethical practice building at Chiropractic Colleges: Part 1: qualitative analysis of opinions from an International Workshop. PMID- 22675221 TI - The JCCA is delighted to announce the recent appointment of Dr. Andre Bussieres DC, PhD candidate to Assistant Editor. PMID- 22675222 TI - Multiple Myeloma presenting as sacroiliac joint pain: a case report. AB - Multiple Myeloma (MM) is the most common primary cancer of bone in adults. The clinical presentation of MM is varied and depends on the sites and extent of involvement. Most importantly for chiropractors, the leading clinical symptoms of MM are related to bone neoplasm and may mimic pain of musculoskeletal origin. The following is the case of a 56 year old male chiropractic patient presenting with a 6 month history of sacroiliac joint pain previously diagnosed and managed unsuccessfully as a hematoma by multiple providers. Physical examination, imaging, and laboratory investigations confirmed a diagnosis of MM. The case report describes relevant pathophysiology, clinical presentation, imaging, and management for MM, while illustrating key issues in patient management as they relate to chiropractic practice and the recognition of pathology in the context of musculoskeletal pain. PMID- 22675223 TI - Pregnancy-related symphysis pubis dysfunction management and postpartum rehabilitation: two case reports. AB - OBJECTIVE: Two case reports review the chiropractic treatment and rehabilitation management of Symphysis Pubis Dysfunction (SPD). CLINICAL FEATURES: Patient 1: a 35-year-old female presented at 30 weeks pregnant with severe left sided Symphysis Pubis Dysfunction and low back pain. Patient 2: a 33-year-old female also 30 weeks pregnant, presented with right sided Symphysis Pubis Dysfunction and sacroiliac pain. INTERVENTION AND OUTCOME: Treatment included soft tissue therapy, pregnancy support belt, side-lying mobilizations, pelvic blocks and instrument-assisted pubic symphysis adjustments. Home advice included: ice, staying active, moving as a unit, stretching, use of a pillow between the knees while sleeping, regular breaks from sitting and pelvic floor (Kegel) exercises. Both patients reported some relief with treatment and home care. Post-partum, rehabilitation exercises were prescribed to restore muscular endurance, control and pelvic stability. On long-term follow-up patient 1 reported no pubic symphysis pain, but some low back pain secondary to a subsequent knee injury. Patient 2 reported being mostly pain free with a rare re-exacerbation of pubic symphysis pain. SUMMARY: Conservative chiropractic management appears to reduce pain and improve mobility and function for SPD. Post partum rehabilitation of the associated lumbo-pelvic musculature with specific stabilization exercises is recommended to reduce pain, improve long term outcomes and prevent chronicity. PMID- 22675224 TI - Conservative management of De Quervain's stenosing tenosynovitis: a case report. AB - OBJECTIVE: To chronicle the conservative treatment and management of a 32-year old female patient presenting with radial wrist pain of 4 months duration, diagnosed as De Quervain's stenosing tenosynovitis. CLINICAL FEATURES: The primary clinical feature is wrist pain at the radial styloid with resultant impairment of wrist, hand, and thumb function. INTERVENTION AND OUTCOME: The conservative treatment approach consisted of activity modification, Graston Technique((r)), and eccentric training. Outcome measures included verbal pain rating scale, QuickDASH Disability/Symptom Score, and a return to activities of daily living (ADLs). The patient attained symptom resolution and at 6 month follow-up reported no recurrence of wrist pain. CONCLUSION: A combination of conservative rehabilitation strategies may be used by chiropractors to treat De Quervain's stenosing tenosynovitis and allow for an individual to return to pain free ADLs in a timely manner. PMID- 22675225 TI - Conservative care of De Quervain's tenosynovitis/ tendinopathy in a warehouse worker and recreational cyclist: a case report. AB - OBJECTIVE: This case study was conducted to evaluate the conservative management of a patient presenting with right sided wrist and thumb pain diagnosed as De Quervain's tenosynovitis/tendinopathy. CLINICAL FEATURES: A 49-year-old female warehouse worker and recreational cyclist with right-sided De Quervain's tenosynovitis/tendinopathy that began after a long-distance cycling trip. INTERVENTION AND OUTCOME: Treatment included ultrasound, soft tissue and myofascial release therapy, tool assisted fascial stripping or "guasha", acupuncture, mobilizations and kinesiology taping. Home advice included icing, rest, wrist bracing, elevation and eccentric rehabilitation exercises. The positive outcome was a complete resolution of the patient's complaint. SUMMARY: This case demonstrates how De Quervain's disease is a challenging condition to treat with conservative methods and can be aggravated with new exacerbating factors as treatment continues. In this case, the addition of the active care (including eccentric exercises and self-care) helped to reinforce the passive care given in the office and accelerate the recovery. PMID- 22675227 TI - Colin A. Greenshields, DC: the Canadian Memorial Chiropractic College's first graduate. AB - This biographical study investigates the complex tribulations and impressive accomplishments of Dr. Colin Greenshields. Part I (the Formative Years) goes back to his ancestors in Great Britain and forward to his graduation from CMCC in 1948. Part II (the Professional Years) begins with the opening of Colin's office in St. Catharines, ON, and proceeds through his professional career and multiple leadership roles to his retirement in 1986. PMID- 22675226 TI - The use of spinal manipulative therapy for pediatric health conditions: a systematic review of the literature. AB - INTRODUCTION: This study had two purposes. These were: (i) to conduct a search of the literature between 2007 and 2011 investigating the use of spinal manipulative therapy (SMT) for pediatric health conditions and (ii) to perform a systematic review of eligible retrieved clinical trials. METHODS: The Index of Chiropractic Literature and PubMed were electronically searched using appropriate search words and MeSH terms, respectively, as well as reference tracking of previous reviews. Studies that met the inclusion criteria were evaluated using an instrument that assessed their methodological quality. RESULTS: Sixteen clinical trials were found that met the inclusion criteria and were scored. DISCUSSION: Six clinical trials investigated the effectiveness of SMT on colic, two each on asthma and enuresis, and one each on hip extension, otitis media, suboptimal breastfeeding, autism, idiopathic scoliosis and jet lag. None investigated the effectiveness of SMT on spinal pain. CONCLUSION: Studies that monitored both subjective and objective outcome measures of relevance to both patients and parents tended to report the most favorable response to SMT, especially among children with asthma. Many studies reviewed suffered from several methodological limitations. Further research is clearly required in this area of chiropractic health care, especially with respect to the clinical effectiveness of SMT on pediatric back pain. PMID- 22675228 TI - Letters to the editor. PMID- 22675229 TI - To the Editor in reply. PMID- 22675230 TI - Single-crystal CVD diamonds as small-angle X-ray scattering windows for high pressure research. AB - Small-angle X-ray scattering (SAXS) was performed on single-crystal chemical vapor deposition (CVD) diamonds with low nitrogen concentrations, which were fabricated by microwave plasma-assisted chemical vapor deposition at high growth rates. High optical quality undoped 500 um-thick single-crystal CVD diamonds grown without intentional nitrogen addition proved to be excellent as windows on SAXS cells, yielding parasitic scattering no more intense than a 7.5 um-thick Kapton film. A single-crystal CVD diamond window was successfully used in a high pressure SAXS cell. PMID- 22675231 TI - Graphical tools for macromolecular crystallography in PHENIX. AB - A new Python-based graphical user interface for the PHENIX suite of crystallography software is described. This interface unifies the command-line programs and their graphical displays, simplifying the development of new interfaces and avoiding duplication of function. With careful design, graphical interfaces can be displayed automatically, instead of being manually constructed. The resulting package is easily maintained and extended as new programs are added or modified. PMID- 22675232 TI - PROSPERO: online prediction of crystallographic success from experimental results and sequence. AB - The growth of diffracting crystals from purified proteins is often a major bottleneck in determining structures of biological and medical interest. The PROSPERO web server, http://skuld.bmsc.washington.edu/prospero, is intended both to provide a means of organizing the potentially large numbers of experimental characterizations measured from such proteins, and to provide useful guidance for structural biologists who have succeeded in purifying their target protein but have reached an impasse in the difficult and poorly understood process of turning purified protein into well diffracting crystals. These researchers need to decide which of many possible rescue options are worth pursuing, given finite resources. This choice is even more crucial when attempting to solve high-priority but relatively difficult structures of eukaryotic proteins. The site currently uses the HyGX1 predictor, which was trained and validated on protein samples from pathogenic protozoa (eukaryotes) using results from six types of experiment. PROSPERO allows users to store, analyze and display multiple results for each sample, to group samples into projects, and to share results and predictions with collaborators. PMID- 22675233 TI - A Preliminary Examination of Sexual Orientation as a Social Vulnerability for Experiencing HIV/AIDS-related Stigma. AB - This investigation is a preliminary examination of sexual orientation as a social vulnerability for experiencing HIV/AIDS-related stigma, specifically concerns about disclosure and public attitudes. Participants were 36 heterosexual men and 82 gay men with HIV/AIDS. Consistent with prediction, a heterosexual sexual orientation was significantly associated with HIV/AIDS disclosure concerns. This effect was evident after controlling for various demographic variables, CD4 T cell count, time since HIV diagnosis, self-esteem, and coping styles. Also, as predicted, similar levels of enacted stigma were evident regardless of sexual orientation. Further work is needed to understand the process of HIV/AIDS disclosure for heterosexual men with this illness and to differentiate the experience of HIV/AIDS-related stigma among gay and straight men with HIV/AIDS. PMID- 22675234 TI - NIR-labeled perfluoropolyether nanoemulsions for drug delivery and imaging. AB - Theranostic nanoparticle development recently took center stage in the field of drug delivery nanoreagent design. Theranostic nanoparticles combine therapeutic delivery systems (liposomes, micelles, nanoemulsions, etc.) with imaging reagents (MRI, optical, PET, CT). This combination allows for non-invasive in vivo monitoring of therapeutic nanoparticles in diseased organs and tissues. Here, we report a novel perfluoropolyether (PFPE) nanoemulsion with a water-insoluble lipophilic drug. The formulation enables non-invasive monitoring of nanoemulsion biodistribution using two imaging modalities, (19)F MRI and near-infrared (NIR) optical imaging. The nanoemulsion is composed of PFPE-tyramide as a (19)F MRI tracer, hydrocarbon oil, surfactants, and a NIR dye. Preparation utilizes a combination of self-assembly and high energy emulsification methods, resulting in droplets with average diameter 180 nm and low polydispersity index (PDI less than 0.2). A model nonsteroidal anti-inflammatory drug (NSAID), celecoxib, was incorporated into the formulation at 0.2 mg/mL. The reported nanoemulsion's properties, including small particle size, visibility under (19)F NMR and NIR fluorescence spectroscopy, and the ability to carry drugs make it an attractive potential theranostic agent for cancer imaging and treatment. PMID- 22675235 TI - Representational Complexity and Memory Retrieval in Language Comprehension. AB - Mental representations formed from words or phrases may vary considerably in their feature-based complexity. Modern theories of retrieval in sentence comprehension do not indicate how this variation and the role of encoding processes should influence memory performance. Here, memory retrieval in language comprehension is shown to be influenced by a target's representational complexity in terms of syntactic and semantic features. Three self-paced reading experiments provide evidence that reading times at retrieval sites (but not earlier) decrease when more complex phrases occur as filler-phrases in filler-gap dependencies. The data also show that complexity-based effects are not dependent on string length, syntactic differences, or the amount of processing the stimuli elicit. Activation boosting and reduced similarity-based interference are implicated as likely sources of these complexity-based effects. PMID- 22675236 TI - Bis(imino)pyridine Iron Dinitrogen Compounds Revisited: Differences in Electronic Structure Between Four- and Five-Coordinate Derivatives. AB - The electronic structures of the four- and five-coordinate aryl-substituted bis(imino)pyridine iron dinitrogen complexes, ((iPr)PDI)FeN(2) and ((iPr)PDI)Fe(N(2))(2) ((iPr)PDI = 2,6-(2,6-(i)Pr(2)-C(6)H(3)-N=CMe)(2)C(5)H(3)N), have been investigated by a combination of spectroscopic techniques (NMR, Mossbauer, X-ray Absorption and X-ray Emission) and DFT calculations. Homologation of the imine methyl backbone to ethyl or isopropyl groups resulted in the preparation of the new bis(imino)pyridine iron dinitrogen complexes, ((iPr)RPDI)FeN(2) ((iPr)RPDI = 2,6-(2,6-(i)Pr(2)-C(6)H(3)-N=CR)(2)C(5)H(3)N; R = Et, (i)Pr), that are exclusively four coordinate both in the solid state and in solution. The spectroscopic and computational data establish that the ((iPr)RPDI)FeN(2) compounds are intermediate spin ferrous derivatives (S(Fe) = 1) antiferromagnetically coupled to bis(imino)pyridine triplet diradical dianions (S(PDI) = 1). While this ground state description is identical to that previously reported for ((iPr)PDI)Fe(DMAP) (DMAP = 4-N,N-dimethylaminopyridine) and other four-coordinate iron compounds with principally sigma-donating ligands, the d orbital energetics determine the degree of coupling of the metal-chelate magnetic orbitals resulting in different NMR spectroscopic behavior. For ((iPr)RPDI)Fe(DMAP) and related compounds, this coupling is strong and results in temperature independent paramagnetism where a triplet excited state mixes with the singlet ground state via spin orbit coupling. In the ((iPr)RPDI)FeN(2) family, one of the iron SOMOs is essentially d(z2) in character resulting in poor overlap with the magnetic orbitals of the chelate, leading to thermal population of the triplet state and hence temperature dependent NMR behavior. The electronic structures of ((iPr)RPDI)FeN(2) and ((iPr)PDI)Fe(DMAP) differ from ((iPr)PDI)Fe(N(2))(2), a highly covalent molecule with a redox non-innocent chelate that is best described as a resonance hybrid between iron(0) and iron(II) canonical forms as originally proposed in 2004. PMID- 22675237 TI - Small-for-Size Liver Transplantation Increases Pulmonary Injury in Rats: Prevention by NIM811. AB - Pulmonary complications after liver transplantation (LT) often cause mortality. This study investigated whether small-for-size LT increases acute pulmonary injury and whether NIM811 which improves small-for-size liver graft survival attenuates LT-associated lung injury. Rat livers were reduced to 50% of original size, stored in UW-solution with and without NIM811 (5 MUM) for 6 h, and implanted into recipients of the same or about twice the donor weight, resulting in half-size (HSG) and quarter-size grafts (QSG), respectively. Liver injury increased and regeneration was suppressed after QSG transplantation as expected. NIM811 blunted these alterations >75%. Pulmonary histological alterations were minimal at 5-18 h after LT. At 38 h, neutrophils and monocytes/macrophage infiltration, alveolar space exudation, alveolar septal thickening, oxidative/nitrosative protein adduct formation, and alveolar epithelial cell/capillary endothelial apoptosis became overt in the lungs of QSG recipients, but these alterations were mild in full-size and HSG recipients. Liver pretreatment with NIM811 markedly decreased pulmonary injury in QSG recipients. Hepatic TNFalpha and IL-1beta mRNAs and pulmonary ICAM-1 expression were markedly higher after QSG transplantation, which were all decreased by NIM811. Together, dysfunctional small-for-size grafts produce toxic cytokines, leading to lung inflammation and injury. NIM811 decreased toxic cytokine formation, thus attenuating pulmonary injury after small-for-size LT. PMID- 22675238 TI - Human mature adipocytes express albumin and this expression is not regulated by inflammation. AB - AIMS: Our group investigated albumin gene expression in human adipocytes, its regulation by inflammation and the possible contribution of adipose tissue to albumin circulating levels. METHODS: Both inflamed and healthy subjects provided adipose tissue samples. RT-PCR, Real-Time PCR, and Western Blot analysis on homogenates of adipocytes and pre-adipocytes were performed. In sixty-three healthy subjects and fifty-four micro-inflamed end stage renal disease (ESRD) patients circulating levels of albumin were measured by nephelometry; all subjects were also evaluated for body composition, calculated from bioelectrical measurements and an thropometric data. RESULTS: A clear gene expression of albumin was showed in pre-adipocytes and, for the first time, in mature adipocytes. Albumin gene expression resulted significantly higher in pre adipocytes than in adipocytes. No significant difference in albumin gene expression was showed between healthy controls and inflamed patients. A significant negative correlation was observed between albumin levels and fat mass in both healthy subjects and inflamed ESRD patients. CONCLUSIONS: In the present study we found first time evidence that human adipocytes express albumin. Our results also showed that systemic inflammation does not modulate albumin gene expression. The negative correlation between albumin and fat mass seems to exclude a significant contributing role of adipocyte in plasma albumin. PMID- 22675239 TI - Integrating Mediators and Moderators in Research Design. AB - The purpose of this article is to describe mediating variables and moderating variables and provide reasons for integrating them in outcome studies. Separate sections describe examples of moderating and mediating variables and the simplest statistical model for investigating each variable. The strengths and limitations of incorporating mediating and moderating variables in a research study are discussed as well as approaches to routinely including these variables in outcome research. The routine inclusion of mediating and moderating variables holds the promise of increasing the amount of information from outcome studies by generating practical information about interventions as well as testing theory. The primary focus is on mediating and moderating variables for intervention research but many issues apply to nonintervention research as well. PMID- 22675240 TI - Gender Differences in Depressive Symptoms During Adolescence: The Contributions of Weight-Related Concerns and Behaviors. AB - A theoretical model of gender differences in depressive symptoms during adolescence was evaluated using data from Waves I and II of the National Longitudinal Study of Adolescent Health. The theoretical model under examination was primarily informed by the gender-additive model of gender differences in depressive symptoms during adolescence proposed by Stice and Bearman (2001). In the model, it was posited that BMI would be associated with perceiving oneself as overweight, which would then lead to a higher probability of dieting, which would be associated with greater depressive symptoms. Participants were 10,864 male and female adolescents. Gender did not moderate any of the model pathways, but mediation analysis indicated that gender differences in changes in depressive symptoms were mediated by perceived weight status and dieting. Findings suggest that one explanation for girls' higher depressive symptoms in adolescence relative to boys is girls' greater tendencies to perceive themselves as overweight and to diet. PMID- 22675241 TI - Pregnancy in HIV-positive patients: effects on vaginal flora. AB - A high proportion of HIV-infected pregnant women present pathogenic organisms in their lower genital tract. This has been associated with the development of postpartum morbility, HIV transmission to the partner and offspring, and other gynaecological conditions, such as cervical dysplasia or cancer. Vaginal flora alterations can range from 47% in Western countries to 89% in Africa in pregnant HIV-positive patients, much higher than about 20% of the general population. Pathogen organism retrieval is high. As peripartum complications due to vaginal infections seem higher in HIV-positive patients, accurate investigation and treatment of such infections are strongly mandatory. PMID- 22675242 TI - Complications of common gynecologic surgeries among HIV-infected women in the United States. AB - OBJECTIVE: To compare frequencies of complications among HIV-infected and uninfected women undergoing common gynecological surgical procedures in inpatient settings. METHODS: We used 1994-2007 data from the Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project, a nationally representative sample of inpatient hospitalizations. Our analysis included discharge records of women aged >=15 undergoing hysterectomy, oophorectomy, salpingectomy for ectopic pregnancy, bilateral tubal sterilization, or dilation and curettage. Associations between HIV infection status and surgical complications were evaluated in multivariable logistic regression models, adjusting for key covariates. RESULTS: For each surgery, HIV infection was associated with experiencing >=1 complication. Adjusted ORs ranged from 2.0 (95% confidence interval (CI): 1.7, 2.2) for hysterectomy with oophorectomy to 3.1 (95% CI: 2.4, 4.0) for bilateral tubal sterilization with no comorbidity present. HIV infection was positively associated with extended length of stay and infectious complications of all of the surgeries examined. For some surgeries, it was positively associated with transfusion and anemia due to acute blood loss. Among HIV-infected women, the odds of infectious and other complications did not decrease between 1994-2000 and 2001-2007. CONCLUSION: HIV infection was associated with elevated frequencies of complications of gynecologic surgeries in the US, even in the era of HAART. PMID- 22675243 TI - In vitro anti-Candida activity of lidocaine and nitroglycerin: alone and combined. AB - The aim of this work was to study the anti-Candida activity of lidocaine and nitroglycerin alone and in combination. Ten Candida strains were included, corresponding to 1 collection type strain (ATCC 10231) and 9 clinical isolates: 4 C. albicans, 2 C. glabrata, 1 C. tropicalis, 1 C. krusei, and 1 C. parapsilosis. The CLSI reference M27-A3 micromethod was used to determine the anti-Candida activity of the drugs alone; minimal inhibitory and lethal concentrations were determined. The classic checkboard technique was used to determine the activity of combined drugs. Lidocaine fungicidal effect was dosedependent. Nitroglycerin exhibited a higher effect. The drugs combination resulted in a reduction of the inhibitory concentration, corresponding to an additive effect. In conclusion, both drugs exhibited an interesting anti-Candida activity. The combination of lidocaine with nitroglycerin was shown to have an additive effect against Candida spp., predicting the interest to include, in the future, these drugs in a new delivery system for the treatment of mucocutaneous candidosis. PMID- 22675245 TI - Selection of ovine oocytes by brilliant cresyl blue staining. AB - Sheep oocytes derived from the ovaries collected from the slaughterhouse are often used for research on in vitro embryo production, animal cloning, transgenesis, embryonic stem cells, and other embryo biotechnology aspects. Improving the in vitro culture efficiency of oocytes can provide more materials for similar studies. Generally, determination of oocyte quality is mostly based on the layers of cumulus cells and cytoplasm or cytoplasm uniformity and colors. This requires considerable experience to better identify oocyte quality because of the intense subjectivity involved (Gordon (2003), Madison et al. (1992) and De Loos et al. (1992)). BCB staining is a function of glucose-6-phosphate dehydrogenase (G6PD) activity, an enzyme synthesized in developing oocytes, which decreases in activity with maturation. Therefore, unstained oocytes (BCB-) are high in G6PD activity, while the less mature oocytes stains are deep blue (BCB+) due to insuffcient G6PD activity to decolorize the BCB dye. PMID- 22675244 TI - In vitro resistance to macrolides and clindamycin by Group B Streptococcus isolated from pregnant and nonpregnant women. AB - BACKGROUND: Despite the introduction of screening bases intrapartum prophylaxis, Streptococcus agalactiae is still an important etiological agent of perinatal infections. The increasing rate of resistance and the differences in resistance pattern among countries suggest that a program of surveillance at the institutional level is important in determining optimal prophylaxis. In contrast, knowledge on GBS epidemiology in Italy is limited, and no data are available in the Southern region of the country. We sought to determine the occurrence of resistance to macrolides and clindamycin of GBS isolates in pregnant and nonpregnant women. METHODS: Between 2005 and 2008, 1346 vaginal and 810 rectovaginal swabs were obtained from pregnant and not-pregnant women. RESULTS: The occurrence of macrolides and clindamycin resistance was 16.5% in 2005 increasing up to 69.9% in 2008. A high percentage of isolates was resistant to tetracycline through all the study period with no statistically significant annual. CONCLUSIONS: In our cohort, an increase of in vitro resistance of GBS to macrolides and clindamycin is clearly evident. The discordance with reports from different countries emphasize the crucial role of microbiological methods in setting possible therapeutic strategies. PMID- 22675246 TI - Eucalyptus biodiesel as an alternative to diesel fuel: preparation and tests on DI diesel engine. AB - Nowadays, the increasing oil consumption throughout the world induces crucial economical, security, and environmental problems. As a result, intensive researches are undertaken to find appropriate substitution to fossil fuels. In view of the large amount of eucalyptus trees present in arid areas, we focus in this study on the investigation of using eucalyptus biodiesel as fuel in diesel engine. Eucalyptus oil is converted by transesterification into biodiesel. Eucalyptus biodiesel characterization shows that the physicochemical properties are comparable to those of diesel fuel. In the second phase, a single cylinder air-cooled, DI diesel engine was used to test neat eucalyptus biodiesel and its blends with diesel fuel in various ratios (75, 50, and 25 by v%) at several engine loads. The engine combustion parameters such as peak pressure, rate of pressure rise, and heat release rate are determined. Performances and exhaust emissions are also evaluated at all operating conditions. Results show that neat eucalyptus biodiesel and its blends present significant improvements of carbon monoxide, unburned hydrocarbon, and particulates emissions especially at high loads with equivalent performances to those of diesel fuel. However, the NOx emissions are slightly increased when the biodiesel content is increased in the blend. PMID- 22675247 TI - The emerging role of PEDF in stem cell biology. AB - Encoded by a single gene, PEDF is a 50 kDa glycoprotein that is highly conserved and is widely expressed among many tissues. Most secreted PEDF deposits within the extracellular matrix, with cell-type-specific functions. While traditionally PEDF is known as a strong antiangiogenic factor, more recently, as this paper highlights, PEDF has been linked with stem cell biology, and there is now accumulating evidence demonstrating the effects of PEDF in a variety of stem cells, mainly in supporting stem cell survival and maintaining multipotency. PMID- 22675248 TI - Finger vein recognition based on (2D)2 PCA and metric learning. AB - Finger vein recognition is a promising biometric recognition technology, which verifies identities via the vein patterns in the fingers. In this paper, (2D)2 PCA is applied to extract features of finger veins, based on which a new recognition method is proposed in conjunction with metric learning. It learns a KNN classifier for each individual, which is different from the traditional methods where a fixed threshold is employed for all individuals. Besides, the SMOTE technology is adopted to solve the class-imbalance problem. Our experiments show that the proposed method is effective by achieving a recognition rate of 99.17%. PMID- 22675249 TI - Multiple signaling pathways are involved in the interleukine-4 regulated expression of DC-SIGN in THP-1 cell line. AB - Dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN) is an important pattern recognition receptor on dendritic cells (DCs), and its expression shows significant cytological and histological specificity, being interleukine-4 (IL-4) dependent. The signaling pathways through which IL-4 regulates expression of DC-SIGN are still unclear. We used phorbol 12-myristate 13-acetate- (PMA-) differentiated THP-1 cells as the in vitro model of monocyte/macrophage cells to study the signaling pathways involved in IL-4 regulated expression of DC-SIGN. We found that a high expression of DC-SIGN could be induced by IL-4 at the levels of mRNA and cell surface protein. Upregulated expression of DC-SIGN was almost completely blocked by the specific inhibitor of ERK pathway, and partly reduced by the specific inhibitors of JAK-STAT and NF kappaB pathways. The activation of the three signaling pathways was directly confirmed by testing the phosphorylation of protein kinase within the cytoplasm and nucleus over time. The analysis of cis-acting elements of DC-SIGN promoter showed that the activity of DC-SIGN promoter without Ets-1 transcription factors binding site almost completely disappeared. Our results demonstrated that multiple signaling pathways are involved in IL-4 induced high expression of DC SIGN on THP-1 cells, in which ERK pathway is the main signaling pathway and mediated by the Ets-1 transcription factors binding site. PMID- 22675250 TI - A standardized extract of Ginkgo biloba neutralizes cisplatin-mediated reproductive toxicity in rats. AB - The aim of this study was to evaluate the protective effects of Ginkgo biloba (GB) against testicular damage and oxidative stress as well as caudal sperm indices in a cisplatin- (CIS-) induced rodent model. Adult male Wistar rats were given vehicle, single i.p. dose of CIS alone (10 mg/kg), GB alone (200 mg g/kg every day for five days), or single dose of CIS followed by GB (50, 100, or 200 mg/kg every day for five days). On day 6, after the first drug treatment oxidative and apoptotic testicular toxicity was evaluated. CIS-treated rats displayed decreased weights of testes and epididymis as well as caudal sperm count and motility. This reproductive toxicity was accompanied with increased germ-cell degeneration in seminiferous tubules and increased germ-cell apoptosis, increased testicular MDA levels and MPO activity, and decreased SOD and CAT activities in testes. Intensive expressions of COX-2, iNOS, and NF-kappaB p65 in testicular tissues were detected in CIS-treated group. Oral GB administrations at all doses to CIS-treated rats effectively alleviated all of the CIS-induced toxicity in reproductive system. The present results provide further insights into the mechanisms of protection against CIS-induced reproductive toxicity and confirm the essential antioxidant potential of a GB extract. PMID- 22675251 TI - Expression of GA733-Fc fusion protein as a vaccine candidate for colorectal cancer in transgenic plants. AB - The tumor-associated antigen GA733 is a cell-surface glycoprotein highly expressed in colorectal carcinomas. In this study, 3 recombinant genes were constructed as follows: GA733 tagged to the ER retention sequence KDEL (GA733K), GA733 fused to the immunoglobulin Fc fragment (GA733-Fc), and GA733-Fc fused to the ER retention sequence (GA733-FcK). Agrobacterium-mediated transformation was used to generate transgenic plants expressing recombinant genes. The presence of transgenes was confirmed by genomic PCR. Western blot, confocal immunofluorescence, and sandwich ELISA showed the expression of recombinant proteins. The stability, flexibility, and bioactivity of recombinant proteins were analyzed and demonstrated through N-glycosylation analysis, animal trials, and sera ELISA. Our results suggest that the KDEL retained proteins in ER with oligomannose glycan structure and enhanced protein accumulation level. The sera of mice immunized with GA733-FcK purified from plants contained immunoglobulins which were at least as efficient as the mammalian-derived GA733-Fc at recognizing human colorectal cancer cell lines. Thus, a plant system can be used to express the KDEL fusion protein with oligomannose glycosylation, and this protein induces an immune response which is comparable to non-KDEL-tagged, mammalian-derived proteins. PMID- 22675252 TI - The impact of Caesarean delivery on paracetamol and ketorolac pharmacokinetics: a paired analysis. AB - Pharmacokinetics is a first, but essential step to improve population-tailored postoperative analgesia, also after Caesarean delivery. We therefore aimed to quantify the impact of caesarean delivery on the pharmacokinetics of intravenous (iv) paracetamol (2 g, single dose) and iv ketorolac tromethamine (30 mg, single dose) in 2 cohorts eachof 8 women at caesarean delivery and to compare these findings with postpartum to quantify intrapatient changes. We documented a higher median paracetamol clearance at delivery when compared to 10-15 weeks postpartum (11.7 to 6.4 L/h.m2, P < 0.01), even after correction for weight-related changes. Similar conclusions were drawn for ketorolac: median clearance was higher at delivery with a subsequent decrease (2.03 to 1.43 L/h.m2, P < 0.05) in postpartum (17-23 weeks). These differences likely reflect pregnancy- and caesarean-delivery related changes in drug disposition. Moreover, postpartum paracetamol clearance was significantly lower when compared to estimates published in healthy young volunteers (6.4 versus 9.6 L/h.m2), while this was not the case for ketorolac (1.43 versus 1.48 L/h.m2). This suggests that postpartum is another specific status in young women that merits focused, compound-specific pharmacokinetic evaluation. PMID- 22675253 TI - Associations of polymorphisms in the apolipoprotein APOA1-C3-A5 gene cluster with acute coronary syndrome. AB - BACKGROUND: Acute coronary syndromes (ACSs) are clinically cardiovascular events associated with dyslipidemia in common. Single nucleotide polymorphisms (SNPs) and haplotypes in the APOA1/C3/A5 gene cluster are associated with diabetes and familial combined hyperlipidaemia (FCH). Little is known about whether the polymorphisms in these genes affect lipid homeostasis in patients with ACSs. The present paper aimed to examine these associations with 4 SNPs in the APOA1 -75G > A, the APOC3 -455T > C, and APOA5 -1131T > C, c.553G > T variant to ACSs in Chinese Han. METHODS: Chinese Han of 229 patients with ACSs and 254 unrelated controls were analyzed. Four SNPs in APOA1/C3/A5 cluster were genotyped and lipid was determined. RESULTS: Our data show that minor allelic frequencies of APOC3 455T > C, APOA5 -1131T > C, and c.553G > T polymorphisms in patients with ACSs were significantly higher than control group (P < 0.05). Furthermore, the 3 polymorphic sites were strongly of linkage disequilibrium, and minor alleles of 3 SNP sites had higher TG level than wild alleles (P < 0.05), APOC3 -455C and APOA5 c.553T allele carriers also had lower level of HDL-C. CONCLUSIONS: The minor alleles of APOC3 -455T > C, APOA5 -1131T > C, and c.553G > T polymorphisms are closely associated with ACSs. PMID- 22675254 TI - Diverse functions of pulmonary collectins in host defense of the lung. AB - Pulmonary surfactant is a mixture of lipids and proteins that covers alveolar surfaces and keeps alveoli from collapsing. Four specific proteins have been identified in surfactant. Among them, two C-type lectins, surfactant proteins A and D (SP-A and SP-D), are known to be implicated in host defense and regulation of inflammatory responses of the lung. These host defense lectins are structurally characterized by N-terminal collagen-like domains and lectin domains and are called pulmonary collectins. They prevent dissemination of infectious microbes by their biological activities including agglutination and growth inhibition. They also promote clearance of microbes by enhancing phagocytosis in macrophages. In addition, they interact with the other pattern-recognition molecules, including Toll-like receptors (TLRs) and TLR-associated molecules, CD14 and MD-2, and regulate inflammatory responses. Furthermore, recent studies have demonstrated that these collectins modulate functions of neutrophil-derived innate immune molecules by interacting with them. These findings indicate that pulmonary collectins play critical roles in host defense of the lung. PMID- 22675255 TI - Advanced computational methods in molecular medicine. PMID- 22675256 TI - A novel aspartic protease with HIV-1 reverse transcriptase inhibitory activity from fresh fruiting bodies of the wild mushroom Xylaria hypoxylon. AB - A novel aspartic protease with HIV-1 RT inhibitory activity was isolated and characterized from fruiting bodies of the wild mushroom Xylaria hypoxylon. The purification protocol comprised distilled water homogenization and extraction step, three ion exchange chromatographic steps (on DEAE-cellulose, Q-Sepharose, and CM-cellulose in succession), and final purification was by FPLC on Superdex 75. The protease was adsorbed on all the three ion exchangers. It was a monomeric protein with a molecular mass of 43 kDa as estimated by SDS-PAGE and FPLC. Its N terminal amino acid sequence was HYTELLSQVV, which exhibited no sequence homology to other proteases reported. The activity of the protease was adversely affected by Pepstatin A, indicating that it is an aspartic protease. The protease activity was maximal or nearly so in the pH range 6-8 and in the temperature range 35-60 degrees C. The purified enzyme exhibited HIV-1 RT inhibitory activity with an IC50 value of 8.3 MUM, but was devoid of antifungal, ribonuclease, and hemagglutinating activities. PMID- 22675258 TI - Comment on "Emerging functions of transcription factors in malaria parasite". PMID- 22675257 TI - Exogenous high-mobility group box 1 protein injection improves cardiac function after myocardial infarction: involvement of Wnt signaling activation. AB - Exogenous high-mobility group box 1 protein (HMGB1) injection could prevent left ventricular remodeling and enhance left ventricular function during myocardial infarction (MI). However, the mechanism remains unclear. This paper was to investigate in the mechanism of cardioprotection of HMGB1 during MI in rats. Anesthetized male rats were treated once with HMGB1 (200 ng) 4 h after MI and then executed after 7 and 28 days, respectively. Cardiac function, collagen deposition, and dishevelled-1 and beta-catenin protein expression were measured. After MI 7 days or 28 days, the left ventricular ejection fraction (LVEF) was significantly decreased compared to that of sham-operated control group (P < 0.05). However, the LVEF HMGB1-treated groups were significantly higher compared to those of the MI group in both 7 days and 28 days (P < 0.05). The collagen volume fraction was significantly reduced in the HMGB1-treated group in infarcted border zone. HMGB1 could activate the expression of dishevelled-1 and beta catenin proteins (P < 0.05). Our study suggested that exogenous high-mobility group box 1 protein injection improves cardiac function after MI, which may be involved in Wnt/beta-catenin signaling activation. PMID- 22675259 TI - Oral lichen planus as a preneoplastic inflammatory model. AB - Oral lichen planus (OLP) is a chronic oral inflammatory disease of unknown etiology. According to reports, 1-2% of OLP patients develop oral squamous cell carcinoma (OSCC) in the long run. While World Health Organization (WHO) classifies OLP as "a potentially malignant disorder," it is still a matter of debate which mechanisms drive OLP to such a condition. The current hypothesis connecting OLP and OSCC is that chronic inflammation results in crucial DNA damage which over time results in cancer development. Initial studies investigating the OLP and OSCC link were mainly retrospective clinical studies. Over the past years, several amount of information has accumulated, mainly from molecular studies on the OLP malignant potential. This article is a critical review of whether OLP has a malignant potential and, therefore, represents a model of preneoplastic inflammation. PMID- 22675261 TI - Update on the development of lurasidone as a treatment for patients with acute schizophrenia. AB - Lurasidone is a novel benzisothiazole antipsychotic drug for the treatment of schizophrenia. Of the antipsychotic drugs, lurasidone has the highest affinity for the 5-hydroxytryptamine (5-HT)(7) receptor. Lurasidone also has high affinities for the dopamine D(2), 5HT(2A), 5-HT(1A) and alpha(2C) adrenergic receptors. Moreover, lurasidone has low affinities for the alpha(1) adrenergic, histamine H(1) and muscarinic M(1) receptors. The involvement of 5-HT(7) receptors in cognitive processes has been suggested by both pharmacological and molecular investigations. Chronic treatment with lurasidone increases neurotrophin BDNF mRNA levels in both the hippocampus (ventral and dorsal) and prefrontal cortex under basal conditions or in response to an acute swim stress. Lurasidone may potentiate N-methyl-D-aspartate receptor (NMDAR) function through antagonistic action on 5-HT(7) receptors without a direct affinity for NMDARs. These results suggest that lurasidone treatment may be a novel approach for the prevention of the development of cognitive impairment in individuals who are at risk for schizophrenia or related disorders involving cognitive impairment. In clinical trials, treatment with lurasidone was associated with significantly greater endpoint improvement versus placebo on the Positive and Negative Syndrome Scale total score after 6 weeks among subjects receiving 80 or 160 mg. The most frequent side effects of lurasidone were akathisia, nausea, parkinsonism, dizziness and somnolence. Once-daily treatment with lurasidone at 160 mg was superior to placebo based on the composite cognitive functioning measure. Lurasidone treatment produced improvements in Montgomery-Asberg Depression Rating Scale scores at 6 weeks that were significantly greater than placebo. A limitation of this review is that the majority of the data were obtained from abstracts and posters. These sources have not been subjected to the peer review processes of medical journals; thus, the results presented in these forums may require further quality review and subsequent revision prior to final publication. PMID- 22675263 TI - New approach to beta cell function screening by nitric oxide assessment of obese individuals at the population level. AB - BACKGROUND: Approximately 27% of Americans today are obese, and this condition increases the prevalence of metabolic syndrome and diabetes. The UK Prospective Diabetes Study suggests that loss of beta cell function can begin at least 10 years before diagnosis, and mean beta cell function is already less than 50% at diagnosis. The aim of this research was to assess the possibility of detecting loss of beta cell function in obese patients by a novel approach involving nitric oxide assessment using a combination of technologies. MATERIALS AND METHODS: One hundred and fifteen obese patients (93 women, 22 men) of mean age 39 (range 17 62) years, who were candidates for bariatric surgery were included in the study, and underwent laboratory tests, including fasting blood glucose, fasting insulin plasma, and examination with the Electro Sensor complex. The Electro Sensor complex offers a new way to assess nitric oxide production using five technologies managed by software, ie, the galvanic skin response, photoelectrical plethysmography, heart rate variability analysis, bioimpedance analysis, and blood pressure oscillometric measurements. The homeostasis model assessment 2% beta cell function (HOMA2% beta) algorithm was calculated from fasting blood glucose and fasting insulin plasma using free software provided by The University of Oxford Diabetes Trial Unit. The Electro Sensor complex percent beta (ESC% beta) algorithm was calculated from the Electro Sensor complex data and statistical neural network. Statistical analysis was performed to correlate ESC% beta and HOMA2% beta using the coefficient of correlation and Spearman's coefficient of rank correlation. Receiver-operating characteristic curves were also constructed to determine the specificity and sensitivity of ESC% beta in detecting a HOMA2% beta value < 100. RESULTS: The coefficient of correlation between ESC% beta and HOMA2% beta was 0.72 (using log values) and the Spearman's coefficient of rank correlation (rho) was 0.799 (P < 0.0001). ESC% beta had a sensitivity of 77.14% and specificity of 78.21% (cutoff <= 157, corresponding to 40% after conversion into a 0%-100% scale) to detect a HOMA2% beta value < 100 (P < 0.0001). CONCLUSION: The ESC% beta algorithm has a high predictive correlation with HOMA2% beta, and good specificity and sensitivity to detect a HOMA2% beta value < 100. Therefore, the Electro Sensor complex enabling nitric oxide assessment represents a novel method of screening for beta cell function in the obese population on a large scale. Such a tool, which is easy to administer, noninvasive, and cost-effective, would be of great benefit for widespread screening of beta cell function in obese patients. PMID- 22675265 TI - Trends in the demographic and clinicopathological characteristics in Japanese patients with endometrial cancer, 1990-2010. AB - OBJECTIVE: Over the past 20 years, the incidence of endometrial cancer has increased remarkably in Japan. The number of elderly females has also increased within the population of Japan. We examined the impact of advanced age on the demographic and clinicopathological characteristics in Japanese patients with endometrial cancer. METHODS: Data were collected from 319 surgically treated Japanese females with endometrial cancer from the files of the University Hospital of Occupational and Environmental Health, Yahatanishi-ku, Kitakyushu, Japan, between 1990 and 2010. chi(2) tests were performed to evaluate the trends in the variables between two decades (A: 116 cases from 1990-2000) and (B: 203 cases in 2001-2010). The histological subtypes were also evaluated based on the immunohistochemical expressions of p53, estrogen receptor, and Ki-67. RESULTS: The mean ages +/- standard deviation in the decade A group and the decade B group were 57.5 years +/- 9.7 years and 61.0 years +/- 11.3 years, respectively (P < 0.02). There was an increase in the proportion of patients aged 70 years or older and of high-risk histological tumors including serous carcinoma, clear cell carcinoma, and carcinosarcoma (decade A group and decade B group: 9.5% vs 27.6%, P < 0.001, 10.4% vs 21.6%, P = 0.01, respectively), while the advanced surgical stage (III and IV), obesity (>=25 of body mass index), and nulliparity of the decade A group and decade B group were 23.3% vs 29.1%, P = 0.30, 28.4% vs 33.0%, P = 0.40, and 19.0% vs 21.2%, P = 0.66, respectively. The cancer-specific survival rates in the decade A group and the decade B group were 78.6% and 77.6%, respectively (P = 0.93). CONCLUSION: The increase in number of elderly females in the Japanese population is related to the increase in that of high-risk endometrial cancers. A study is needed to investigate prevention strategies and to improve the treatment of elderly patients with high-risk endometrial cancer. PMID- 22675264 TI - Update on the clinical utility and optimal use of cefditoren. AB - This article reviews and updates published data on cefditoren. The in vitro activity of cefditoren and its potential pharmacokinetic/pharmacodynamic adequacy to cover emerging resistance phenotypes in the present decade is reviewed. Cefditoren's in vitro activity against most prevalent bacterial respiratory pathogens in the community and its pharmacokinetic/pharmacodynamic profile suggests a significant role for cefditoren in the treatment of respiratory tract infections. Clinical trials (in acute exacerbations of chronic bronchitis, community-acquired pneumonia, pharyngotonsillitis, and sinusitis) performed during clinical development outside Japan, mainly in adults, are reviewed, together with new clinical studies in the treatment of pharyngotonsillitis, sinusitis, and otitis media in children, mainly in Japan, for efficacy and safety assessment. The results of these studies support the adequacy of cefditoren for the treatment of community-acquired respiratory tract infections with a safety profile similar to previous oral antibiotics. From the data reviewed, it is concluded that cefditoren is an adequate option for the treatment of mild-to moderate community-acquired respiratory infections, especially in geographical areas with a reported prevalence of phenotypes exhibiting nonsusceptibility to common oral antibiotics. PMID- 22675266 TI - Understanding lupus nephritis: diagnosis, management, and treatment options. AB - Systemic lupus erythematosus (SLE) predominantly affects women in their reproductive years. Renal disease (glomerulonephritis) is one of the most frequent and serious manifestations of SLE. Of the various histological types of lupus glomerulonephritis, diffuse proliferative nephritis carries the worst prognosis. Combined with high-dose prednisone, mycophenolate mofetil (MMF) has emerged as a first-line immunosuppressive treatment, although data regarding the efficacy of MMF on the long-term preservation of renal function are forthcoming. Cyclophosphamide is reserved for more severe forms of lupus nephritis, such as crescentic glomerulonephritis with rapidly deteriorating renal function, patients with significant renal function impairment at presentation, and refractory renal disease. Evidence for the calcineurin inhibitors in the treatment of lupus nephritis is weaker, and it concerns patients who are intolerant or recalcitrant to other agents. While further controlled trials are mandatory, B cell modulation therapies, such as rituximab, belimumab and epratuzumab are confined to refractory disease. Non-immunosuppressive measures, such as angiotensin converting enzyme inhibitors, vigorous blood pressure control, prevention and treatment of hyperlipidemia and osteoporosis, are equally important. PMID- 22675267 TI - Laparoscopic management of a large torted ovarian cyst in an adolescent virgin: a case report. AB - We report a case of a torted mature cystic teratoma in a 23-year-old, sexually inactive, virgin female which necessitated immediate laparoscopy. The patient and her family stressed that the integrity of the hymen must be maintained at any cost, for cultural reasons. We opted out of our routine intravaginal preparation for laparoscopic surgery to honor the patient's request to maintain the integrity of the hymen. Left salpingo-oophorectomy was accomplished, and the specimen was removed using a large nephrectomy endobag. Here, we describe techniques that are useful for this procedure, including the use of gauze attached to ovum forceps to manipulate the uterus through the rectum, and a review of the literature. PMID- 22675268 TI - Married men's perceptions of barriers for HIV-positive pregnant women accessing highly active antiretroviral therapy in rural Uganda. AB - BACKGROUND: The aim of this study was to describe the perceptions of married men about barriers to accessing and accepting highly active antiretroviral therapy (HAART) by pregnant/postnatal women positive for human immunodeficiency virus (HIV) and registered in Kabarole District's Program for the Prevention of HIV from Mother to Child (PMTCT-Plus). MATERIALS AND METHODS: Our study was a qualitative descriptive exploratory study using thematic analysis. Four focus group discussions were held with a convenience sample of 40 married men. RESULTS: Lack of disclosure of a positive HIV diagnosis to the partner and stigmatization of persons with HIV were two major obstacles for women in accessing HAART. In addition, men felt that their low knowledge of HAART and their low HIV testing rate also constituted important barriers to these women taking treatment. Men complained that they were not sufficiently involved in the reproductive care of women and that couples' counseling could be a step towards addressing this problem. CONCLUSION: Barriers to HAART experienced by pregnant/postnatal women need to be addressed in order to improve their uptake of treatment, increase their low treatment coverage, improve their survival, and at the same time dramatically reduce HIV transmission from mother to child. PMID- 22675269 TI - Prenatal diagnosis of an aneurysm of the vein of galen by three-dimensional power and color Doppler ultrasonography. AB - Aneurism of the vein of Galen is a complex arteriovenous malformation which is of multiply communications between of the vein of Galen and the cerebral arteries. It represents less than 1% of the cerebral arteriovenous malformations. Few cases using three-dimensional (3D) power and color Doppler ultrasound have been reported in the literature. We present a case of an aneurysm of the vein of Galen diagnosed at 25th week of pregnancy. We demonstrate the main findings of 3D power and color Doppler ultrasonography in this anomaly. A 36-year-old pregnant woman, gravida 3, para 2 was referred to our institution because of a midline cystic mass diagnosed in a previous ultrasonography undertaken at 24 weeks' gestation. The ultrasonographic finding consisted of a male fetus with a midline cystic mass, with positive flow detection by color Doppler and ventriculomegaly due to the compressive effects of the malformation. The 3D color and power Doppler ultrasonography allowed us to reconstruct the architecture of the vascular malformation, and it showed the spatial relationships of aneurysm of the vein of Galen with the other structures of the brain. Pregnancy was interrupted at 29 weeks' gestation because of presence of cardiomegaly. A male newborn survived for 36 hours only. The 3D ultrasound can be used as advent image technique in prenatal diagnosis of aneurysm of the vein of Galen. PMID- 22675270 TI - A Sensor System for Automatic Detection of Food Intake Through Non-Invasive Monitoring of Chewing. AB - Objective and automatic sensor systems to monitor ingestive behavior of individuals arise as a potential solution to replace inaccurate method of self report. This paper presents a simple sensor system and related signal processing and pattern recognition methodologies to detect periods of food intake based on non-invasive monitoring of chewing. A piezoelectric strain gauge sensor was used to capture movement of the lower jaw from 20 volunteers during periods of quiet sitting, talking and food consumption. These signals were segmented into non overlapping epochs of fixed length and processed to extract a set of 250 time and frequency domain features for each epoch. A forward feature selection procedure was implemented to choose the most relevant features, identifying from 4 to 11 features most critical for food intake detection. Support vector machine classifiers were trained to create food intake detection models. Twenty-fold cross-validation demonstrated per-epoch classification accuracy of 80.98% and a fine time resolution of 30 s. The simplicity of the chewing strain sensor may result in a less intrusive and simpler way to detect food intake. The proposed methodology could lead to the development of a wearable sensor system to assess eating behaviors of individuals. PMID- 22675271 TI - Leukoaraiosis is a chronic atherosclerotic disease. AB - BACKGROUND AND PURPOSE: White matter changes (WMCs), or leukoaraiosis (LA), are associated with increased age, hypertension, diabetes mellitus, and history of stroke. Although several lines of evidence suggest a role of atherosclerosis in atherothrombotic vascular events, their involvement in LA remains to be determined. Our study examines this association in ischemic stroke patients. METHODS: One hundred and seventy consecutive ischemic stroke or transient ischemic attack (TIA) patients were included. All patients underwent brain computed tomography (CT) with assessment of the extension and severity of WMCs, carotid arteries duplex scan with measurements of intima-media thickness (IMT) and plaques. RESULTS: Seventy-two patients (42.4%) were found to have white matter lesions, of whom 28.8% had advanced LA. Mean IMT was significantly higher in patients with LA and with advanced LA (P = 0.002, P = 0.003, resp.). In addition, LA and LA severity were associated with existence of carotid plaque (P = 0.007, P = 0.004, resp.). In multivariate logistic regression analysis, including all vascular risk factors, LA was found to be associated with age and IMT. CONCLUSION: This study reinforces the tight association between LA and carotid atherosclerosis in ischemic stroke patients. We conclude that a chronic atherosclerotic disease underlies the pathophysiology of leukoaraiosis and its progression. PMID- 22675272 TI - Bedside calculation of energy expenditure does not guarantee adequate caloric prescription in long-term mechanically ventilated critically ill patients: a quality control study. AB - Nutrition is essential in critically ill patients, but translating caloric prescriptions into adequate caloric intake remains challenging. Caloric prescriptions (P), effective intake (I), and caloric needs (N), calculated with modified Harris-Benedict formulas, were recorded during seven consecutive days in ventilated patients. Adequacy of prescription was estimated by P/N ratio. I/P ratio assessed accuracy of translating a prescription into administered feeding. I/N ratio compared delivered calories with theoretical caloric needs. Fifty patients were prospectively studied in a mixed medicosurgical ICU in a teaching hospital. Basal and total energy expenditure were, respectively, 1361 +/- 171 kcal/d and 1649 +/- 233 kcal/d. P and I attained 1536 +/- 602 kcal/d and 1424 +/- 572 kcal/d, respectively. 24.6% prescriptions were accurate, and 24.3% calories were correctly administered. Excessive calories were prescribed in 35.4% of patients, 27.4% being overfed. Caloric needs were underestimated in 40% prescriptions, with 48.3% patients underfed. Calculating caloric requirements by a modified standard formula covered energy needs in only 25% of long-term mechanically ventilated patients, leaving many over- or underfed. Nutritional imbalance mainly resulted from incorrect prescription. Failure of "simple" calculations to direct caloric prescription in these patients suggests systematic use of more reliable methods, for example, indirect calorimetry. PMID- 22675277 TI - Letter from the editor. PMID- 22675273 TI - Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK): explanation and elaboration. AB - The REMARK (Reporting Recommendations for Tumor Marker Prognostic Studies) guideline includes a checklist which aims to improve the reporting of these types of studies. Here, we expand on the REMARK checklist to enhance its use and effectiveness through better understanding of the intent of each item and why the information is important to report. Each checklist item of the REMARK guideline is explained in detail and accompanied by published examples of good reporting. The paper provides a comprehensive overview to educate on good reporting and provide a valuable reference of issues to consider when designing, conducting, and analyzing tumor marker studies and prognostic studies in medicine in general. PMID- 22675274 TI - Structure and functional analysis of the RNA- and viral phosphoprotein-binding domain of respiratory syncytial virus M2-1 protein. AB - Respiratory syncytial virus (RSV) protein M2-1 functions as an essential transcriptional cofactor of the viral RNA-dependent RNA polymerase (RdRp) complex by increasing polymerase processivity. M2-1 is a modular RNA binding protein that also interacts with the viral phosphoprotein P, another component of the RdRp complex. These binding properties are related to the core region of M2-1 encompassing residues S58 to K177. Here we report the NMR structure of the RSV M2 1(58-177) core domain, which is structurally homologous to the C-terminal domain of Ebola virus VP30, a transcription co-factor sharing functional similarity with M2-1. The partial overlap of RNA and P interaction surfaces on M2-1(58-177), as determined by NMR, rationalizes the previously observed competitive behavior of RNA versus P. Using site-directed mutagenesis, we identified eight residues located on these surfaces that are critical for an efficient transcription activity of the RdRp complex. Single mutations of these residues disrupted specifically either P or RNA binding to M2-1 in vitro. M2-1 recruitment to cytoplasmic inclusion bodies, which are regarded as sites of viral RNA synthesis, was impaired by mutations affecting only binding to P, but not to RNA, suggesting that M2-1 is associated to the holonucleocapsid by interacting with P. These results reveal that RNA and P binding to M2-1 can be uncoupled and that both are critical for the transcriptional antitermination function of M2-1. PMID- 22675279 TI - Psychosocial factors contributing to inflammatory bowel disease activity and health-related quality of life. AB - OBJECTIVE: This study aimed to examine the contributions of coping and social constraint to disease activity and health-related quality of life (HRQOL) and to examine group differences in disease activity and HRQOL between patients with high versus low anxiety or depression symptoms in adults with inflammatory bowel disease (IBD). METHODS: This study was a retrospective analysis in which disease activity was measured with either the Harvey-Bradshaw Index or the Simple Clinical Colitis Activity Index. HRQOL was measured with the Short Inflammatory Bowel Disease Questionnaire. Coping was measured with a modified COPE questionnaire. Anxiety and depression symptoms were measured with the Hospital Anxiety and Depression Scale. Social constraint was measured with the Social Constraint Questionnaire. Correlational and regression analyses were performed to assess the relationships between social constraint, coping, anxiety symptoms, depression symptoms, and HRQOL and disease activity. RESULTS: Data from 80 adults with IBD were reviewed. Social constraint, disengagement coping, anxiety symptoms, and depression symptoms were inversely correlated with HRQOL. Disengagement coping was positively correlated with disease activity. Regression analyses showed that smokers had significantly worse HRQOL than nonsmokers and that greater use of engagement coping was associated with significantly diminished HRQOL. Regression analyses also showed that patients diagnosed between 17 and 40 years of age were significantly less likely to have active disease than patients diagnosed before 16 years of age and that greater use of disengagement coping was associated with increased odds of having active disease. CONCLUSIONS: Medical providers should be aware that coexisting social constraint and symptoms of anxiety and depression are common in patients with IBD. Screening for these factors, as well as patients' coping styles, should be strongly considered, and patients should be referred to mental health providers as appropriate. PMID- 22675278 TI - Acute liver failure in adults: an evidence-based management protocol for clinicians. AB - With the goal of providing guidance on the provision of optimal intensive care to adult patients with acute liver failure (ALF), this paper defines ALF and describes a protocol for appropriately diagnosing this relatively rare clinical entity and ascertaining its etiology, where possible. This paper also identifies the few known therapies that may be effective for specific causes of ALF and provides a comprehensive approach for anticipating, identifying, and managing complications. Finally, one of the more important aspects of care for patients with ALF is the determination of prognosis and, specifically, the need for liver transplantation. Prognostic tools are provided to help guide the clinician in this critical decision process. Management of patients with ALF is complex and challenging, even in centers where staff members have high levels of expertise and substantial experience. This evidence-based protocol may, therefore, assist in the delivery of optimal care to this critically ill patient population and may substantially increase the likelihood of positive outcomes. PMID- 22675280 TI - Use of protease inhibitors in liver transplant recipients. PMID- 22675281 TI - Use of symptom indices in the management of GERD. PMID- 22675282 TI - Quality indicators in colonoscopy practice. PMID- 22675283 TI - Fecal transplantation for the treatment of Clostridium difficile infection. PMID- 22675284 TI - A case of cronkhite-Canada syndrome and a review of gastrointestinal polyposis syndromes. PMID- 22675285 TI - Cronkhite-Canada syndrome: an acquired condition of gastrointestinal polyposis and dermatologic abnormalities. PMID- 22675286 TI - Subacute liver failure secondary to amyloid light-chain amyloidosis. PMID- 22675287 TI - Amyloidosis and subacute liver failure. PMID- 22675288 TI - Glycemic index and glycemic load are associated with some cardiovascular risk factors among the PREMIER study participants. AB - BACKGROUND: The clinical significance of glycemic index (GI) and glycemic load (GL) is inconclusive. OBJECTIVE: This study was conducted to examine the association of GI and GL with clinical cardiovascular disease (CVD) risk factors including body weight, blood pressure (BP), serum lipids, fasting glucose, insulin and homocysteine over time among the PREMIER participants. DESIGN: PREMIER was an 18-month randomized lifestyle intervention trial, conducted from 2000 to 2002, designed to help participants reduce BP by following the Dietary Approaches to Stop Hypertension (DASH) dietary pattern, losing weight, reducing sodium and increasing physical activity. GI and GL were estimated from 24 h diet recall data at baseline, 6 and 18 months after intervention. PROC MIXED model was used to examine the association of changes in GI or GL with changes in CVD risk factors. RESULTS: A total of 756 randomized participants, 62% females and 34% African Americans and who averaged 50.0+/-0.3 years old and 95.3+/-0.7 kg, were included in this report. Neither GI nor GL changes was associated with changes in any risk factors at 6 months. At 18 months, however, the GI change was significantly and positively associated with total cholesterol (TC) change only (p<0.05, beta=23.80+/-12.11 mg/dL or 0.62+/-0.31 mmol/L) with a significant age interaction. The GL change was significantly associated with TC (p=0.02, beta=0.28+/-0.15 mg/dL or 0.01+/-0.00 mmol/L) positively and with low density lipoprotein cholesterol (LDL-C) changes negatively (p=0.03, beta=-0.01+/-0.00 mg/dL or -0.00+/-0.00 mmol/L), and significant age interactions were observed for both. CONCLUSIONS: GI and GL was associated with TC and LDL-C after controlling for energy, fat and fiber intake and other potential confounders and the associations were modified by age. Further investigation into this relationship is important because of its potential clinical impact. PMID- 22675289 TI - Decreasing ventromedial prefrontal cortex activity during sequential risk-taking: an FMRI investigation of the balloon analog risk task. AB - Functional imaging studies examining the neural correlates of risk have mainly relied on paradigms involving exposure to simple chance gambles and an economic definition of risk as variance in the probability distribution over possible outcomes. However, there is little evidence that choices made during gambling tasks predict naturalistic risk-taking behaviors such as drug use, extreme sports, or even equity investing. To better understand the neural basis of naturalistic risk-taking, we scanned participants using fMRI while they completed the Balloon Analog Risk Task, an experimental measure that includes an active decision/choice component and that has been found to correlate with a number of naturalistic risk-taking behaviors. In the task, as in many naturalistic settings, escalating risk-taking occurs under uncertainty and might be experienced either as the accumulation of greater potential rewards, or as exposure to increasing possible losses (and decreasing expected value). We found that areas previously linked to risk and risk-taking (bilateral anterior insula, anterior cingulate cortex, and right dorsolateral prefrontal cortex) were activated as participants continued to inflate balloons. Interestingly, we found that ventromedial prefrontal cortex (vmPFC) activity decreased as participants further expanded balloons. In light of previous findings implicating the vmPFC in value calculation, this result suggests that escalating risk-taking in the task might be perceived as exposure to increasing possible losses (and decreasing expected value) rather than the increasing potential total reward relative to the starting point of the trial. A better understanding of how neural activity changes with risk-taking behavior in the task offers insight into the potential neural mechanisms driving naturalistic risk-taking. PMID- 22675291 TI - Brain-computer interfaces: a neuroscience paradigm of social interaction? A matter of perspective. AB - A number of recent studies have put human subjects in true social interactions, with the aim of better identifying the psychophysiological processes underlying social cognition. Interestingly, this emerging Neuroscience of Social Interactions (NSI) field brings up challenges which resemble important ones in the field of Brain-Computer Interfaces (BCI). Importantly, these challenges go beyond common objectives such as the eventual use of BCI and NSI protocols in the clinical domain or common interests pertaining to the use of online neurophysiological techniques and algorithms. Common fundamental challenges are now apparent and one can argue that a crucial one is to develop computational models of brain processes relevant to human interactions with an adaptive agent, whether human or artificial. Coupled with neuroimaging data, such models have proved promising in revealing the neural basis and mental processes behind social interactions. Similar models could help BCI to move from well-performing but offline static machines to reliable online adaptive agents. This emphasizes a social perspective to BCI, which is not limited to a computational challenge but extends to all questions that arise when studying the brain in interaction with its environment. PMID- 22675290 TI - All in the Family: How the APPs Regulate Neurogenesis. AB - Recent intriguing evidence suggests that metabolites of amyloid precursor protein (APP), mutated in familial forms of Alzheimer's disease (AD), play critical roles in developmental and postnatal neurogenesis. Of note is soluble APPalpha (sAPPalpha) that regulates neural progenitor cell proliferation. The APP family encompasses a group of ubiquitously expressed and evolutionarily conserved, type I transmembrane glycoproteins, whose functions have yet to be fully elucidated. APP can undergo proteolytic cleavage by mutually exclusive pathways. The subtle structural differences between metabolites generated in the different pathways, as well as their equilibrium, may be crucial for neuronal function. The implications of this new body of evidence are significant. Miscleavage of APP would readily impact developmental and postnatal neurogenesis, which might contribute to cognitive deficits characterizing Alzheimer's disease. This review will discuss the implications of the role of the APP family in neurogenesis for neuronal development, cognitive function, and brain disorders that compromise learning and memory, such as AD. PMID- 22675292 TI - High classification accuracy for schizophrenia with rest and task FMRI data. AB - We present a novel method to extract classification features from functional magnetic resonance imaging (fMRI) data collected at rest or during the performance of a task. By combining a two-level feature identification scheme with kernel principal component analysis (KPCA) and Fisher's linear discriminant analysis (FLD), we achieve high classification rates in discriminating healthy controls from patients with schizophrenia. Experimental results using leave-one out cross-validation show that features extracted from the default mode network (DMN) lead to a classification accuracy of over 90% in both data sets. Moreover, using a majority vote method that uses multiple features, we achieve a classification accuracy of 98% in auditory oddball (AOD) task and 93% in rest data. Several components, including DMN, temporal, and medial visual regions, are consistently present in the set of features that yield high classification accuracy. The features we have extracted thus show promise to be used as biomarkers for schizophrenia. Results also suggest that there may be different advantages to using resting fMRI data or task fMRI data. PMID- 22675293 TI - Games people play-toward an enactive view of cooperation in social neuroscience. AB - The field of social neuroscience has made considerable progress in unraveling the neural correlates of human cooperation by making use of brain imaging methods. Within this field, neuroeconomic research has drawn on paradigms from experimental economics, such as the Prisoner's Dilemma (PD) and the Trust Game. These paradigms capture the topic of conflict in cooperation, while focusing strongly on outcome-related decision processes. Cooperation, however, does not equate with that perspective, but relies on additional psychological processes and events, including shared intentions and mutually coordinated joint action. These additional facets of cooperation have been successfully addressed by research in developmental psychology, cognitive science, and social philosophy. Corresponding neuroimaging data, however, is still sparse. Therefore, in this paper, we present a juxtaposition of these mutually related but mostly independent trends in cooperation research. We propose that the neuroscientific study of cooperation could benefit from paradigms and concepts employed in developmental psychology and social philosophy. Bringing both to a neuroimaging environment might allow studying the neural correlates of cooperation by using formal models of decision-making as well as capturing the neural responses that underlie joint action scenarios, thus, promising to advance our understanding of the nature of human cooperation. PMID- 22675294 TI - On Variability and Genes: Inter-individual Differences in Auditory Brain Function. PMID- 22675295 TI - Social top-down response modulation (STORM): a model of the control of mimicry in social interaction. AB - As a distinct feature of human social interactions, spontaneous mimicry has been widely investigated in the past decade. Research suggests that mimicry is a subtle and flexible social behavior which plays an important role for communication and affiliation. However, fundamental questions like why and how people mimic still remain unclear. In this paper, we evaluate past theories of why people mimic and the brain systems that implement mimicry in social psychology and cognitive neuroscience. By reviewing recent behavioral and neuroimaging studies on the control of mimicry by social signals, we conclude that the subtlety and sophistication of mimicry in social contexts reflect a social top-down response modulation (STORM) which increases one's social advantage and this mechanism is most likely implemented by medial prefrontal cortex (mPFC). We suggest that this STORM account of mimicry is important for our understanding of social behavior and social cognition, and provides implications for future research in autism. PMID- 22675296 TI - High frequency deep brain stimulation attenuates subthalamic and cortical rhythms in Parkinson's disease. AB - Parkinson's disease (PD) is marked by excessive synchronous activity in the beta (8-35 Hz) band throughout the cortico-basal ganglia network. The optimal location of high frequency deep brain stimulation (HF DBS) within the subthalamic nucleus (STN) region and the location of maximal beta hypersynchrony are currently matters of debate. Additionally, the effect of STN HF DBS on neural synchrony in functionally connected regions of motor cortex is unknown and is of great interest. Scalp EEG studies demonstrated that stimulation of the STN can activate motor cortex antidromically, but the spatial specificity of this effect has not been examined. The present study examined the effect of STN HF DBS on neural synchrony within the cortico-basal ganglia network in patients with PD. We measured local field potentials dorsal to and within the STN of PD patients, and additionally in the motor cortex in a subset of these patients. We used diffusion tensor imaging (DTI) to guide the placement of subdural cortical surface electrodes over the DTI-identified origin of the hyperdirect pathway (HDP) between motor cortex and the STN. The results demonstrated that local beta power was attenuated during HF DBS both dorsal to and within the STN. The degree of attenuation was monotonic with increased DBS voltages in both locations, but this voltage-dependent effect was greater in the central STN than dorsal to the STN (p < 0.05). Cortical signals over the estimated origin of the HDP also demonstrated attenuation of beta hypersynchrony during DBS dorsal to or within STN, whereas signals from non-specific regions of motor cortex were not attenuated. The spatially-specific suppression of beta synchrony in the motor cortex support the hypothesis that DBS may treat Parkinsonism by reducing excessive synchrony in the functionally connected sensorimotor network. PMID- 22675297 TI - Oscillatory Brain Correlates of Live Joint Attention: A Dual-EEG Study. AB - Joint attention consists in following another's gaze onto an environmental object, which leads to the alignment of both subjects' attention onto this object. It is a fundamental mechanism of non-verbal communication, and it is essential for dynamic, online, interindividual synchronization during interactions. Here we aimed at investigating the oscillatory brain correlates of joint attention in a face-to-face paradigm where dyads of participants dynamically oriented their attention toward the same or different objects during joint and no-joint attention periods respectively. We also manipulated task instruction: in socially driven instructions, the participants had to follow explicitly their partner's gaze, while in color-driven instructions, the objects to be looked at were designated at by their color so that no explicit gaze following was required. We focused on oscillatory activities in the 10 Hz frequency range, where parieto-occipital alpha and the centro-parietal mu rhythms have been described, as these rhythms have been associated with attention and social coordination processes respectively. We tested the hypothesis of a modulation of these oscillatory activities by joint attention. We used dual-EEG to record simultaneously the brain activities of the participant dyads during our live, face-to-face joint attention paradigm. We showed that joint attention periods - as compared to the no-joint attention periods - were associated with a decrease of signal power between 11 and 13 Hz over a large set of left centro parieto-occipital electrodes, encompassing the scalp regions where alpha and mu rhythms have been described. This 11-13 Hz signal power decrease was observed independently of the task instruction: it was similar when joint versus no-joint attention situations were socially driven and when they were color-driven. These results are interpreted in terms of the processes of attention mirroring, social coordination, and mutual attentiveness associated with joint attention state. PMID- 22675298 TI - What representations and computations underpin the contribution of the hippocampus to generalization and inference? AB - Empirical research and theoretical accounts have traditionally emphasized the function of the hippocampus in episodic memory. Here we draw attention to the importance of the hippocampus to generalization, and focus on the neural representations and computations that might underpin its role in tasks such as the paired associate inference (PAI) paradigm. We make a principal distinction between two different mechanisms by which the hippocampus may support generalization: an encoding-based mechanism that creates overlapping representations which capture higher-order relationships between different items [e.g., Temporal Context Model (TCM): Howard et al., 2005]-and a retrieval-based model [Recurrence with Episodic Memory Results in Generalization (REMERGE): Kumaran and McClelland, in press] that effectively computes these relationships at the point of retrieval, through a recurrent mechanism that allows the dynamic interaction of multiple pattern separated episodic codes. We also discuss what we refer to as transfer effects-a more abstract example of generalization that has also been linked to the function of the hippocampus. We consider how this phenomenon poses inherent challenges for models such as TCM and REMERGE, and outline the potential applicability of a separate class of models-hierarchical Bayesian models (HBMs) in this context. Our hope is that this article will provide a basic framework within which to consider the theoretical mechanisms underlying the role of the hippocampus in generalization, and at a minimum serve as a stimulus for future work addressing issues that go to the heart of the function of the hippocampus. PMID- 22675299 TI - A mutual information approach to automate identification of neuronal clusters in Drosophila brain images. AB - Mapping neural circuits can be accomplished by labeling a small number of neural structures per brain, and then combining these structures across multiple brains. This sparse labeling method has been particularly effective in Drosophila melanogaster, where clonally related clusters of neurons derived from the same neural stem cell (neuroblast clones) are functionally related and morphologically highly stereotyped across animals. However identifying these neuroblast clones (approximately 180 per central brain hemisphere) manually remains challenging and time consuming. Here, we take advantage of the stereotyped nature of neural circuits in Drosophila to identify clones automatically, requiring manual annotation of only an initial, smaller set of images. Our procedure depends on registration of all images to a common template in conjunction with an image processing pipeline that accentuates and segments neural projections and cell bodies. We then measure how much information the presence of a cell body or projection at a particular location provides about the presence of each clone. This allows us to select a highly informative set of neuronal features as a template that can be used to detect the presence of clones in novel images. The approach is not limited to a specific labeling strategy and can be used to identify partial (e.g., individual neurons) as well as complete matches. Furthermore this approach could be generalized to studies of neural circuits in other organisms. PMID- 22675300 TI - Tyrosine phosphorylation of botulinum neurotoxin protease domains. AB - Botulinum neurotoxins are most potent of all toxins. Their N-terminal light chain domain (Lc) translocates into peripheral cholinergic neurons to exert its endoproteolytic action leading to muscle paralysis. Therapeutic development against these toxins is a major challenge due to their in vitro and in vivo structural differences. Although three-dimensional structures and reaction mechanisms are very similar, the seven serotypes designated A through G vastly vary in their intracellular catalytic stability. To investigate if protein phosphorylation could account for this difference, we employed Src-catalyzed tyrosine phosphorylation of the Lc of six serotypes namely LcA, LcB, LcC1, LcD, LcE, and LcG. Very little phosphorylation was observed with LcD and LcE but LcA, LcB, and LcG were maximally phosphorylated by Src. Phosphorylation of LcA, LcB, and LcG did not affect their secondary and tertiary structures and thermostability significantly. Phosphorylation of Y250 and Y251 made LcA resistant to autocatalysis and drastically reduced its k(cat)/K(m) for catalysis. A tyrosine residue present near the essential cysteine at the C-terminal tail of LcA, LcB, and LcG was readily phosphorylated in vitro. Inclusion of a competitive inhibitor protected Y426 of LcA from phosphorylation, shedding light on the role of the C-terminus in the enzyme's substrate or product binding. PMID- 22675302 TI - Introduction to multifractal detrended fluctuation analysis in matlab. AB - Fractal structures are found in biomedical time series from a wide range of physiological phenomena. The multifractal spectrum identifies the deviations in fractal structure within time periods with large and small fluctuations. The present tutorial is an introduction to multifractal detrended fluctuation analysis (MFDFA) that estimates the multifractal spectrum of biomedical time series. The tutorial presents MFDFA step-by-step in an interactive Matlab session. All Matlab tools needed are available in Introduction to MFDFA folder at the website www.ntnu.edu/inm/geri/software. MFDFA are introduced in Matlab code boxes where the reader can employ pieces of, or the entire MFDFA to example time series. After introducing MFDFA, the tutorial discusses the best practice of MFDFA in biomedical signal processing. The main aim of the tutorial is to give the reader a simple self-sustained guide to the implementation of MFDFA and interpretation of the resulting multifractal spectra. PMID- 22675301 TI - Extrasynaptic neurotransmission in the modulation of brain function. Focus on the striatal neuronal-glial networks. AB - Extrasynaptic neurotransmission is an important short distance form of volume transmission (VT) and describes the extracellular diffusion of transmitters and modulators after synaptic spillover or extrasynaptic release in the local circuit regions binding to and activating mainly extrasynaptic neuronal and glial receptors in the neuroglial networks of the brain. Receptor-receptor interactions in G protein-coupled receptor (GPCR) heteromers play a major role, on dendritic spines and nerve terminals including glutamate synapses, in the integrative processes of the extrasynaptic signaling. Heteromeric complexes between GPCR and ion-channel receptors play a special role in the integration of the synaptic and extrasynaptic signals. Changes in extracellular concentrations of the classical synaptic neurotransmitters glutamate and GABA found with microdialysis is likely an expression of the activity of the neuron-astrocyte unit of the brain and can be used as an index of VT-mediated actions of these two neurotransmitters in the brain. Thus, the activity of neurons may be functionally linked to the activity of astrocytes, which may release glutamate and GABA to the extracellular space where extrasynaptic glutamate and GABA receptors do exist. Wiring transmission (WT) and VT are fundamental properties of all neurons of the CNS but the balance between WT and VT varies from one nerve cell population to the other. The focus is on the striatal cellular networks, and the WT and VT and their integration via receptor heteromers are described in the GABA projection neurons, the glutamate, dopamine, 5-hydroxytryptamine (5-HT) and histamine striatal afferents, the cholinergic interneurons, and different types of GABA interneurons. In addition, the role in these networks of VT signaling of the energy-dependent modulator adenosine and of endocannabinoids mainly formed in the striatal projection neurons will be underlined to understand the communication in the striatal cellular networks. PMID- 22675304 TI - I.4 Screening Experimental Designs for Quantitative Trait Loci, Association Mapping, Genotype-by Environment Interaction, and Other Investigations. AB - Crop breeding programs using conventional approaches, as well as new biotechnological tools, rely heavily on data resulting from the evaluation of genotypes in different environmental conditions (agronomic practices, locations, and years). Statistical methods used for designing field and laboratory trials and for analyzing the data originating from those trials need to be accurate and efficient. The statistical analysis of multi-environment trails (MET) is useful for assessing genotype * environment interaction (GEI), mapping quantitative trait loci (QTLs), and studying QTL * environment interaction (QEI). Large populations are required for scientific study of QEI, and for determining the association between molecular markers and quantitative trait variability. Therefore, appropriate control of local variability through efficient experimental design is of key importance. In this chapter we present and explain several classes of augmented designs useful for achieving control of variability and assessing genotype effects in a practical and efficient manner. A popular procedure for unreplicated designs is the one known as "systematically spaced checks." Augmented designs contain "c" check or standard treatments replicated "r" times, and "n" new treatments or genotypes included once (usually) in the experiment. PMID- 22675303 TI - Recent insights into muscle fatigue at the cross-bridge level. AB - The depression in force and/or velocity associated with muscular fatigue can be the result of a failure at any level, from the initial events in the motor cortex of the brain to the formation of an actomyosin cross-bridge in the muscle cell. Since all the force and motion generated by muscle ultimately derives from the cyclical interaction of actin and myosin, researchers have focused heavily on the impact of the accumulation of intracellular metabolites [e.g., P(i), H(+) and adenosine diphoshphate (ADP)] on the function these contractile proteins. At saturating Ca(++) levels, elevated P(i) appears to be the primary cause for the loss in maximal isometric force, while increased [H(+)] and possibly ADP act to slow unloaded shortening velocity in single muscle fibers, suggesting a causative role in muscular fatigue. However the precise mechanisms through which these metabolites might affect the individual function of the contractile proteins remain unclear because intact muscle is a highly complex structure. To simplify problem isolated actin and myosin have been studied in the in vitro motility assay and more recently the single molecule laser trap assay with the findings showing that both P(i) and H(+) alter single actomyosin function in unique ways. In addition to these new insights, we are also gaining important information about the roles played by the muscle regulatory proteins troponin (Tn) and tropomyosin (Tm) in the fatigue process. In vitro studies, suggest that both the acidosis and elevated levels of P(i) can inhibit velocity and force at sub saturating levels of Ca(++) in the presence of Tn and Tm and that this inhibition can be greater than that observed in the absence of regulation. To understand the molecular basis of the role of regulatory proteins in the fatigue process researchers are taking advantage of modern molecular biological techniques to manipulate the structure and function of Tn/Tm. These efforts are beginning to reveal the relevant structures and how their functions might be altered during fatigue. Thus, it is a very exciting time to study muscle fatigue because the technological advances occurring in the fields of biophysics and molecular biology are providing researchers with the ability to directly test long held hypotheses and consequently reshaping our understanding of this age-old question. PMID- 22675305 TI - Cobalt-Protoporphyrin Improves Heart Function by Blunting Oxidative Stress and Restoring NO Synthase Equilibrium in an Animal Model of Experimental Diabetes. AB - Myocardial dysfunction and coronary macro/microvascular alterations are the hallmarks of diabetic cardiomyopathy and are ascribed to increased oxidative stress and altered nitric oxide synthase (NOS) activity. We hypothesize that pre treatment by cobalt-protoporphyrin IX (CoPP) ameliorates both myocardial function and coronary circulation in streptozotocin (STZ)-induced diabetic rats. Isolated hearts from diabetic rats in Langendorff configuration displayed lower left ventricular function and higher coronary resistance (CR) compared to hearts from control animals. CoPP treatment of diabetic animals (0.3 mg/100 g body weight i.p., once a week for 3 weeks) significantly increased all the contractile/relaxation indexes (p < 0.01), while decreasing CR (p < 0.01). CoPP enhanced HO-1 protein levels and reduced oxidative stress in diabetic animals, as indicated by the significant (p < 0.05) decrease in heart % GSSG, [Formula: see text] and malondialdehyde (MDA) levels. CoPP increased adiponectin levels and phosphorylation of AKT and AMPK and reversed the eNOS/iNOS expression imbalance observed in the untreated diabetic heart. Furthermore, after CoPP treatment, a rise in malonyl-CoA as well as a decrease in acetyl-CoA was observed in diabetic hearts. In this experimental model of diabetic cardiomyopathy, CoPP treatment improved both cardiac function and coronary flow by blunting oxidative stress, restoring eNOS/iNOS expression balance and increasing HO-1 levels, thereby favoring improvement in both endothelial function and insulin sensitivity. PMID- 22675306 TI - Decompression vs. Decomposition: Distribution, Amount, and Gas Composition of Bubbles in Stranded Marine Mammals. AB - Gas embolic lesions linked to military sonar have been described in stranded cetaceans including beaked whales. These descriptions suggest that gas bubbles in marine mammal tissues may be more common than previously thought. In this study we have analyzed gas amount (by gas score) and gas composition within different decomposition codes using a standardized methodology. This broad study has allowed us to explore species-specific variability in bubble prevalence, amount, distribution, and composition, as well as masking of bubble content by putrefaction gases. Bubbles detected within the cardiovascular system and other tissues related to both pre- and port-mortem processes are a common finding on necropsy of stranded cetaceans. To minimize masking by putrefaction gases, necropsy, and gas sampling must be performed as soon as possible. Before 24 h post mortem is recommended but preferably within 12 h post mortem. At necropsy, amount of bubbles (gas score) in decomposition code 2 in stranded cetaceans was found to be more important than merely presence vs. absence of bubbles from a pathological point of view. Deep divers presented higher abundance of gas bubbles, mainly composed of 70% nitrogen and 30% CO(2), suggesting a higher predisposition of these species to suffer from decompression-related gas embolism. PMID- 22675307 TI - Phenotyping chickpeas and pigeonpeas for adaptation to drought. AB - The chickpea and pigeonpea are protein-rich grain legumes used for human consumption in many countries. Grain yield of these crops is low to moderate in the semi-arid tropics with large variation due to high GxE interaction. In the Indian subcontinent chickpea is grown in the post-rainy winter season on receding soil moisture, and in other countries during the cool and dry post winter or spring seasons. The pigeonpea is sown during rainy season which flowers and matures in post-rainy season. The rainy months are hot and humid with diurnal temperature varying between 25 and 35 degrees C (maximum) and 20 and 25 degrees C (minimum) with an erratic rainfall. The available soil water during post-rainy season is about 200-250 mm which is bare minimum to meet the normal evapotranspiration. Thus occurrence of drought is frequent and at varying degrees. To enhance productivity of these crops cultivars tolerant to drought need to be developed. ICRISAT conserves a large number of accessions of chickpea (>20,000) and pigeonpea (>15,000). However only a small proportion (<1%) has been used in crop improvement programs mainly due to non-availability of reliable information on traits of economic importance. To overcome this, core and mini core collections (10% of core, 1% of entire collection) have been developed. Using the mini core approach, trait-specific donor lines were identified for agronomic, quality, and stress related traits in both crops. Composite collections were developed both in chickpea (3000 accessions) and pigeonpea (1000 accessions), genotyped using SSR markers and genotype based reference sets of 300 accessions selected for each crop. Screening methods for different drought tolerant traits such as early maturity (drought escape), large and deep root system, high water-use efficiency, smaller leaflets, reduced canopy temperature, carbon isotope discrimination, high leaf chlorophyll content (drought avoidance), and breeding strategies for improving drought tolerance have been discussed. PMID- 22675308 TI - Analysis of constituents for phenotyping drought tolerance in crop improvement. AB - Investigators now have a wide range of analytical tools to use in measuring metabolites, proteins and transcripts in plant tissues. These tools have the potential to assist genetic studies that seek to phenotype genetic lines for heritable traits that contribute to drought tolerance. To be useful for crop breeding, hundreds or thousands of genetic lines must be assessed. This review considers the utility of assaying certain constituents with roles in drought tolerance for phenotyping genotypes. Abscisic acid (ABA), organic and inorganic osmolytes, compatible solutes, and late embryogenesis abundant proteins, are considered. Confounding effects that require appropriate tissue and timing specificity, and the need for high-throughput and analytical cost efficiency are discussed. With future advances in analytical methods and the value of analyzing constituents that provide information on the underlying mechanisms of drought tolerance, these approaches are expected to contribute to development crops with improved drought tolerance. PMID- 22675309 TI - Mechanistic insights into aging, cell-cycle progression, and stress response. AB - The longevity of an organism depends on the health of its cells. Throughout life cells are exposed to numerous intrinsic and extrinsic stresses, such as free radicals, generated through mitochondrial electron transport, and ultraviolet irradiation. The cell has evolved numerous mechanisms to scavenge free radicals and repair damage induced by these insults. One mechanism employed by the yeast Saccharomycescerevisiae to combat stress utilizes the Anaphase Promoting Complex (APC), an essential multi-subunit ubiquitin-protein ligase structurally and functionally conserved from yeast to humans that controls progression through mitosis and G1. We have observed that yeast cells expressing compromised APC subunits are sensitive to multiple stresses and have shorter replicative and chronological lifespans. In a pathway that runs parallel to that regulated by the APC, members of the Forkhead box (Fox) transcription factor family also regulate stress responses. The yeast Fox orthologs Fkh1 and Fkh2 appear to drive the transcription of stress response factors and slow early G1 progression, while the APC seems to regulate chromatin structure, chromosome segregation, and resetting of the transcriptome in early G1. In contrast, under non-stress conditions, the Fkhs play a complex role in cell-cycle progression, partially through activation of the APC. Direct and indirect interactions between the APC and the yeast Fkhs appear to be pivotal for lifespan determination. Here we explore the potential for these interactions to be evolutionarily conserved as a mechanism to balance cell-cycle regulation with stress responses. PMID- 22675310 TI - Using multivariate machine learning methods and structural MRI to classify childhood onset schizophrenia and healthy controls. AB - INTRODUCTION: Multivariate machine learning methods can be used to classify groups of schizophrenia patients and controls using structural magnetic resonance imaging (MRI). However, machine learning methods to date have not been extended beyond classification and contemporaneously applied in a meaningful way to clinical measures. We hypothesized that brain measures would classify groups, and that increased likelihood of being classified as a patient using regional brain measures would be positively related to illness severity, developmental delays, and genetic risk. METHODS: Using 74 anatomic brain MRI sub regions and Random Forest (RF), a machine learning method, we classified 98 childhood onset schizophrenia (COS) patients and 99 age, sex, and ethnicity-matched healthy controls. We also used RF to estimate the probability of being classified as a schizophrenia patient based on MRI measures. We then explored relationships between brain-based probability of illness and symptoms, premorbid development, and presence of copy number variation (CNV) associated with schizophrenia. RESULTS: Brain regions jointly classified COS and control groups with 73.7% accuracy. Greater brain-based probability of illness was associated with worse functioning (p = 0.0004) and fewer developmental delays (p = 0.02). Presence of CNV was associated with lower probability of being classified as schizophrenia (p = 0.001). The regions that were most important in classifying groups included left temporal lobes, bilateral dorsolateral prefrontal regions, and left medial parietal lobes. CONCLUSION: Schizophrenia and control groups can be well classified using RF and anatomic brain measures, and brain-based probability of illness has a positive relationship with illness severity and a negative relationship with developmental delays/problems and CNV-based risk. PMID- 22675312 TI - Combined Induction of Rubber-Hand Illusion and Out-of-Body Experiences. AB - The emergence of self-consciousness depends on several processes: those of body ownership, attributing self-identity to the body, and those of self-location, localizing our sense of self. Studies of phenomena like the rubber-hand illusion (RHi) and out-of-body experience (OBE) investigate these processes, respectively for representations of a body-part and the full-body. It is supposed that RHi only target processes related to body-part representations, while OBE only relates to full-body representations. The fundamental question whether the body part and the full-body illusions relate to each other is nevertheless insufficiently investigated. In search for a link between body-part and full-body illusions in the brain we developed a behavioral task combining adapted versions of the RHi and OBE. Furthermore, for the investigation of this putative link we investigated the role of sensory and motor cues. We established a spatial dissociation between visual and proprioceptive feedback of a hand perceived through virtual reality in rest or action. Two experimental measures were introduced: one for the body-part illusion, the proprioceptive drift of the perceived localization of the hand, and one for the full-body illusion, the shift in subjective-straight-ahead (SSA). In the rest and action conditions it was observed that the proprioceptive drift of the left hand and the shift in SSA toward the manipulation side are equivalent. The combined effect was dependent on the manipulation of the visual representation of body parts, rejecting any main or even modulatory role for relevant motor programs. Our study demonstrates for the first time that there is a systematic relationship between the body-part illusion and the full-body illusion, as shown by our measures. This suggests a link between the representations in the brain of a body-part and the full-body, and consequently a common mechanism underpinning both forms of ownership and self location. PMID- 22675311 TI - ABC Transporters and the Alzheimer's Disease Enigma. AB - Alzheimer's disease (AD) is considered the "disease of the twenty-first century." With a 10-fold increase in global incidence over the past 100 years, AD is now reaching epidemic proportions and by all projections, AD patient numbers will continue to rise. Despite intense research efforts, AD remains a mystery and effective therapies are still unavailable. This represents an unmet need resulting in clinical, social, and economic problems. Over the last decade, a new AD research focus has emerged: ATP-binding cassette (ABC) transporters. In this article, we provide an overview of the ABC transporters ABCA1, ABCA2, P glycoprotein (ABCB1), MRP1 (ABCC1), and BCRP (ABCG2), all of which are expressed in the brain and have been implicated in AD. We summarize recent findings on the role of these five transporters in AD, and discuss their potential to serve as therapeutic targets. PMID- 22675314 TI - Bilingual word recognition in a sentence context. AB - This article provides an overview of bilingualism research on visual word recognition in isolation and in sentence context. Many studies investigating the processing of words out-of-context have shown that lexical representations from both languages are activated when reading in one language (language-non-selective lexical access). A newly developed research line asks whether language-non selective access generalizes to word recognition in sentence contexts, providing a language cue and/or semantic constraint information for upcoming words. Recent studies suggest that the language of the preceding words is insufficient to restrict lexical access to words of the target language, even when reading in the native language. Eye tracking studies revealing the time course of word activation further showed that semantic constraint does not restrict language-non selective access at early reading stages, but there is evidence that it has a relatively late effect. The theoretical implications for theories of bilingual word recognition are discussed in light of the Bilingual Interactive Activation+ model (Dijkstra and van Heuven, 2002). PMID- 22675313 TI - Continuous cognitive dynamics of the evaluation of trustworthiness in williams syndrome. AB - The decision to approach or avoid an unfamiliar person is based in part on one's evaluation of facial expressions. Individuals with Williams syndrome (WS) are characterized in part by an excessive desire to approach people, but they display deficits in identifying facial emotional expressions. Likert-scale ratings are generally used to examine approachability ratings in WS, but these measures only capture an individual's final approach/avoid decision. The present study expands on previous research by utilizing mouse-tracking methodology to visually display the nature of approachability decisions via the motor movement of a computer mouse. We recorded mouse movement trajectories while participants chose to approach or avoid computer-generated faces that varied in terms of trustworthiness. We recruited 30 individuals with WS and 30 chronological age matched controls (mean age = 20 years). Each participant performed 80 trials (20 trials each of four face types: mildly and extremely trustworthy; mildly and extremely untrustworthy). We found that individuals with WS were significantly more likely than controls to choose to approach untrustworthy faces. In addition, WS participants considered approaching untrustworthy faces significantly more than controls, as evidenced by their larger maximum deviation, before eventually choosing to avoid the face. Both the WS and control participants were able to discriminate between mild and extreme degrees of trustworthiness and were more likely to make correct approachability decisions as they grew older. These findings increase our understanding of the cognitive processing that underlies approachability decisions in individuals with WS. PMID- 22675315 TI - Remembering another aspect of forgetting. AB - Although forgetting is most often thought of in terms of declines in performance (response loss or impairment), another class of memory phenomena, the forgetting of stimulus attributes, has begun to attract experimental attention. In non-human animals, the loss of memory for stimulus features is reflected in the flattening of stimulus generalization gradients as well as in the attenuation of the disrupting effect of a shift in context at testing. In both cases, a delay between the learning episode and testing results in increased responding in the presence of previously ineffective stimuli. Thus, previously discriminable cues become more functionally interchangeable. The implications of the forgetting of attributes for some theoretical issues of memory loss and for methodological strategies have been noted earlier. However, relatively little is known about the neurobiological mechanisms underlying stimulus attribute forgetting, and why some memories are maintained while others are not. In this paper we review the evidence for the forgetting of stimulus attributes, discuss recent findings identifying neurobiological underpinnings of forgetting and generalization of fear responses, and discuss relevant clinical implications of fear generalization. PMID- 22675317 TI - The importance of replication in comparative psychology: the lesson of elephant quantity judgments. PMID- 22675316 TI - Task-dependent masked priming effects in visual word recognition. AB - A method used widely to study the first 250 ms of visual word recognition is masked priming: These studies have yielded a rich set of data concerning the processes involved in recognizing letters and words. In these studies, there is an implicit assumption that the early processes in word recognition tapped by masked priming are automatic, and masked priming effects should therefore be invariant across tasks. Contrary to this assumption, masked priming effects are modulated by the task goal: For example, only word targets show priming in the lexical decision task, but both words and non-words do in the same-different task; semantic priming effects are generally weak in the lexical decision task but are robust in the semantic categorization task. We explain how such task dependence arises within the Bayesian Reader account of masked priming (Norris and Kinoshita, 2008), and how the task dissociations can be used to understand the early processes in lexical access. PMID- 22675318 TI - Sleep - more local and complex than previously thought? PMID- 22675320 TI - Mycoreovirus genome alterations: similarities to and differences from rearrangements reported for other reoviruses. AB - The family Reoviridae is one of the largest virus families with genomes composed of 9-12 double-stranded RNA segments. It includes members infecting organisms from protists to humans. It is well known that reovirus genomes are prone to various types of genome alterations including intragenic rearrangement and reassortment under laboratory and natural conditions. Recently distinct genetic alterations were reported for members of the genus Mycoreovirus, Mycoreovirus 1 (MyRV1), and MyRV3 with 11 (S1-S11) and 12 genome segments (S1-S12), respectively. While MyRV3 S8 is lost during subculturing of infected host fungal strains, MyRV1 rearrangements undergo alterations spontaneously and inducibly. The inducible MyRV1 rearrangements are different from any other previous examples of reovirus rearrangements in their dependence on an unrelated virus factor, a multifunctional protein, p29, encoded by a distinct virus Cryphonectria parasitica hypovirus 1 (CHV1). A total of 5 MyRV1 variants with genome rearranged segments (S1-S3, S6 and S10) are generated in the background of a single viral strain in the presence of CHV1 p29 supplied either transgenically or by coinfection. MyRV1 S4 and S10 are rearranged, albeit very infrequently, in a CHV1 p29 independent fashion. A variant of MyRV1 with substantial deletions in both S4 and S10, generated through a combined reassortment and rearrangement approach, shows comparable replication levels to the wild-type MyRV1. In vivo and in vitro interactions of CHV1 p29 and MyRV1 VP9 are implicated in the induction of MyRV1 rearrangements. However, the mechanism underlying p29-mediated rearrangements remains largely unknown. MyRV1 S4 rearrangements spontaneously occurred independently of CHV1 p29. In the absence of reverse genetics systems for mycoreoviruses, molecular and biological characterization of these MyRV1 and MyRV3 variants contribute to functional analyses of the protein products encoded by those rearranged segments. PMID- 22675319 TI - Thyroid hormone deiodinases and cancer. AB - Deiodinases constitute a group of thioredoxin fold-containing selenoenzymes that play an important function in thyroid hormone homeostasis and control of thyroid hormone action. There are three known deiodinases: D1 and D2 activate the pro hormone thyroxine (T4) to T3, the most active form of thyroid hormone, while D3 inactivates thyroid hormone and terminates T3 action. A number of studies indicate that deiodinase expression is altered in several types of cancers, suggesting that (i) they may represent a useful cancer marker and/or (ii) could play a role in modulating cell proliferation - in different settings thyroid hormone modulates cell proliferation. For example, although D2 is minimally expressed in human and rodent skeletal muscle, its expression level in rhabdomyosarcoma (RMS)-13 cells is threefold to fourfold higher. In basal cell carcinoma (BCC) cells, sonic hedgehog (Shh)-induced cell proliferation is accompanied by induction of D3 and inactivation of D2. Interestingly a fivefold reduction in the growth of BCC in nude mice was observed if D3 expression was knocked down. A decrease in D1 activity has been described in renal clear cell carcinoma, primary liver cancer, lung cancer, and some pituitary tumors, while in breast cancer cells and tissue there is an increase in D1 activity. Furthermore D1 mRNA and activity were found to be decreased in papillary thyroid cancer while D1 and D2 activities were significantly higher in follicular thyroid cancer tissue, in follicular adenoma, and in anaplastic thyroid cancer. It is conceivable that understanding how deiodinase dysregulation in tumor cells affect thyroid hormone signaling and possibly interfere with tumor progression could lead to new antineoplastic approaches. PMID- 22675321 TI - Biogenic amines in raw and processed seafood. AB - The presence of biogenic amines (BAs) in raw and processed seafood, associated with either time/temperature conditions or food technologies is discussed in the present paper from a safety and prevention point of view. In particular, storage temperature, handling practices, presence of microbial populations with decarboxylase activity and availability of free amino acids are considered the most important factors affecting the production of BAs in raw seafood. On the other hand, some food technological treatments such as salting, ripening, fermentation, or marination can increase the levels of BAs in processed seafood. The consumption of high amount of BAs, above all histamine, can result in food borne poisoning which is a worldwide problem. The European Regulation established as maximum limits for histamine, in fishery products from fish species associated with high histidine amounts, values ranging from 100 to 200 mg/kg, while for products which have undergone enzyme maturation treatment in brine, the aforementioned limits rise to 200 and 400 mg/kg. Preventive measures and emerging methods aiming at controlling the production of BAs are also reported for potential application in seafood industries. PMID- 22675322 TI - Antibody Peptide based antifungal immunotherapy. AB - Fungal infections still represent relevant human illnesses worldwide and some are accompanied by unacceptably high mortality rates. The limited current availability of effective and safe antifungal agents makes the development of new drugs and approaches of antifungal vaccination/immunotherapy every day more needed. Among them, small antibody(Ab)-derived peptides are arousing great expectations as new potential antifungal agents. In this topic, the search path from the study of the yeast killer phenomenon to the production of Ab-derived peptides characterized by in vitro and in vivo fungicidal activity will be focused. In particular, Abs that mimic the antimicrobial activity of a killer toxin ("antibiobodies") and antifungal peptides derived from antibiobodies (killer peptide) and other unrelated Abs [complementarity determining regions (CDR)-based and constant region (Fc)-based synthetic peptides] are described. Mycological implications in terms of reevaluation of the yeast killer phenomenon, roles of antibiobodies in antifungal immunity, of beta-glucans as antifungal targets and vaccines, and of Abs as sources of an unlimited number of sequences potentially active as new immunotherapeutic tools against fungal agents and related mycoses, are discussed. PMID- 22675323 TI - Impact of hfq on the intrinsic drug resistance of salmonella enterica serovar typhimurium. AB - Salmonella enterica is an important enteric pathogen, and its various serovars cause both systemic and intestinal diseases in humans and domestic animals. The emergence of multidrug-resistant strains of Salmonella, leading to increased morbidity and mortality, has further complicated its management. Hfq is an RNA chaperon that mediates the binding of small RNAs to mRNA and assists in post transcriptional gene regulation in bacteria. Although Hfq is related to important phenotypes including virulence in Salmonella, its role in the drug resistance of this organism is unknown. The aim of this study was to investigate the role of Hfq in intrinsic drug resistance of S. enterica serovar Typhimurium. hfq Mutant was susceptible to acriflavine. Although there is a relationship between the production of the AcrB multidrug efflux pump and Hfq in Escherichia coli, the deletion of the drug efflux acrB did not impair the effect of hfq deletion on Salmonella susceptibility. In contrast, the deletion of another drug efflux gene, smvA, impaired the effect of hfq deletion on acriflavine susceptibility. These results indicate that Hfq regulates the intrinsic drug resistance, and it may influence drug susceptibility by regulating SmvA in Salmonella. PMID- 22675324 TI - TH17 Cells in Autoimmunity and Immunodeficiency: Protective or Pathogenic? AB - In 2005 a newly discovered T helper cell subset that secreted interleukin (IL)-17 became the center of attention in immunology. Initial studies painted Th17 cells as the culprit for destruction in many different autoimmune and auto-inflammatory diseases. Subsequently, the discovery of patients with primary immunodeficiencies in the IL-17 pathway taught us that Th17 cells have a critical role in defense against certain fungal and bacterial infections. Moreover, the paradoxical exacerbation of Crohn's disease in the clinical trials of a Secukinumab (AIN457), a fully human neutralizing antibody to IL-17A, has cast into doubt a universal pro-inflammatory and harmful role for Th17 cells. Evidence now suggests that depending on the environment Th17 cells can alter their differentiation program, ultimately giving rise to either protective or pro-inflammatory cells. In this review we will summarize the evidence from patients with immunodeficiencies, autoimmune, or auto-inflammatory diseases that teaches us how the pro inflammatory versus protective function of Th17 cells varies within the context of different human diseases. PMID- 22675325 TI - Mast cell adenosine receptors function: a focus on the a3 adenosine receptor and inflammation. AB - Adenosine is a metabolite, which has long been implicated in a variety of inflammatory processes. Inhaled adenosine provokes bronchoconstriction in asthmatics or chronic obstructive pulmonary disease patients, but not in non asthmatics. This hyper responsiveness to adenosine appears to be mediated by mast cell activation. These observations have marked the receptor that mediates the bronchoconstrictor effect of adenosine on mast cells (MCs), as an attractive drug candidate. Four subtypes (A1, A2a, A2b, and A3) of adenosine receptors have been cloned and shown to display distinct tissue distributions and functions. Animal models have firmly established the ultimate role of the A3 adenosine receptor (A3R) in mediating hyper responsiveness to adenosine in MCs, although the influence of the A2b adenosine receptor was confirmed as well. In contrast, studies of the A3R in humans have been controversial. In this review, we summarize data on the role of different adenosine receptors in mast cell regulation of inflammation and pathology, with a focus on the common and distinct functions of the A3R in rodent and human MCs. The relevance of mouse studies to the human is discussed. PMID- 22675326 TI - Intracellular events regulating cross-presentation. AB - Cross-presentation plays a fundamental role in the induction of CD8-T cell immunity. However, although more than three decades have passed since its discovery, surprisingly little is known about the exact mechanisms involved. Here we give an overview of the components involved at different stages of this process. First, antigens must be internalized into the cross-presenting cell. The involvement of different receptors, method of antigen uptake, and nature of the antigen can influence intracellular trafficking and access to the cross presentation pathway. Once antigens access the endocytic system, different requirements for endosomal/phagosomal processing arise, such as proteolysis and reduction of disulfide bonds. The majority of cross-presented peptides are generated by proteasomal degradation. Therefore, antigens must cross a membrane barrier in a manner analogous to the fate of misfolded proteins in the endoplasmic reticulum (ER) that are retrotranslocated into the cytosol for degradation. Indeed, some components of the ER-associated degradation machinery have been implicated in cross-presentation. Further complicating the matter, endosomal and phagosomal compartments have been suggested as alternative sites to the ER for loading of peptides on major histocompatibility complex class I molecules. Finally, the antigen presenting cells involved, particularly dendritic cell subsets and their state of maturation, influence the efficiency of cross presentation. PMID- 22675327 TI - Opposing roles for heat and heat shock proteins in macrophage functions during inflammation: a function of cell activation state? AB - Macrophages function both under normothermia and during periods of body temperature elevation (fever). Whether macrophages sense and respond to thermal signals in a manner which regulates their function in a specific manner is still not clear. In this brief review, we highlight recent studies which have analyzed the effects of mild heating on macrophage cytokine production, and summarize thermally sensitive molecular mechanisms, such as heat shock protein (HSP) expression, which have been identified. Mild, physiologically achievable, hyperthermia has been shown to have both pro- and anti-inflammatory effects on macrophage inflammatory cytokine production and overall it is not clear how hyperthermia or HSPs can exert opposing roles on macrophage function. We propose here that the stage of activation of macrophages predicts how they respond to mild heating and the specific manner in which HSPs function. Continuing research in this area is needed which will help us to better understand the immunological role of body temperature shifts. Such studies could provide a scientific basis for the use of heat in treatment of inflammatory diseases. PMID- 22675329 TI - DNA-Based Genetic Markers for Rapid Cycling Brassica Rapa (Fast Plants Type) Designed for the Teaching Laboratory. AB - We have developed DNA-based genetic markers for rapid cycling Brassica rapa (RCBr), also known as Fast Plants. Although markers for B. rapa already exist, ours were intentionally designed for use in a teaching laboratory environment. The qualities we selected for were robust amplification in PCR, polymorphism in RCBr strains, and alleles that can be easily resolved in simple agarose slab gels. We have developed two single nucleotide polymorphism (SNP) based markers and 14 variable number tandem repeat (VNTR)-type markers spread over four chromosomes. The DNA sequences of these markers represent variation in a wide range of genomic features. Among the VNTR-type markers, there are examples of variation in a non-genic region, variation within an intron, and variation in the coding sequence of a gene. Among the SNP-based markers there are examples of polymorphism in intronic DNA and synonymous substitution in a coding sequence. Thus these markers can serve laboratory exercises in both transmission genetics and molecular biology. PMID- 22675328 TI - The role of Th cell subsets in the control of Helicobacter infections and in T cell-driven gastric immunopathology. AB - Chronic infection with the gastric bacterial pathogen Helicobacter pylori causes gastric adenocarcinoma in a particularly susceptible fraction of the infected population. The intestinal type of gastric cancer is preceded by a series of preneoplastic lesions that are of immunopathological origin, and that can be recapitulated by experimental infection of C57BL/6 mice with Helicobacter species. Several lines of evidence suggest that specific T cell subsets and/or their signature cytokines contribute to the control of Helicobacter infections on the one hand, and to the associated gastric preneoplastic pathology on the other. Here, we have used virulent H. pylori and H. felis isolates to infect mice that lack alpha/beta T cells due to a targeted deletion of the T cell receptor beta chain, or are deficient for the unique p35 and p19 subunits of the Th1- and Th17 polarizing cytokines interleukin (IL)-12 and IL-23, respectively. We found that alpha/beta T cells are absolutely required for Helicobacter control and for the induction of gastric preneoplastic pathology. In contrast, neither IL-12 dependent Th1 nor IL-23-dependent Th17 cells were essential for controlling the infection; IL-12p35(-/-) and IL-23p19(-/-) mice did not differ significantly from wild type animals with respect to Helicobacter colonization densities. Gastritis and gastric preneoplastic pathology developed to a similar extent in all three strains upon H. felis infection; in the H. pylori infection model, IL-23p19(-/-) mice exhibited significantly less gastritis and precancerous pathology. In summary, the results indicate that neither Th1 nor Th17 cells are by themselves essential for Helicobacter control; the associated gastric pathology is reduced only in the absence of Th17-polarizing IL-23, and only in the H. pylori, but not the H. felis infection model. The results thus suggest the involvement of other, as yet unknown T cell subsets in both processes. PMID- 22675330 TI - Humble Thanks to a Gentle Giant (an Obituary for James F. Crow). PMID- 22675332 TI - Modulation of microRNA Activity by Semi-microRNAs. AB - The ribonuclease Dicer plays a central role in the microRNA pathway by catalyzing the formation of 19-24-nucleotide (nt) long microRNAs. Subsequently incorporated into Argonaute 2 (Ago2) effector complexes, microRNAs are known to regulate messenger RNA (mRNA) translation. Whether shorter RNA species derived from microRNAs exist and play a role in mRNA regulation remains unknown. Here, we report the serendipitous discovery of a 12-nt long RNA species corresponding to the 5' region of the microRNA let-7, and tentatively termed semi-microRNA, or smiRNA. Using a smiRNA derived from the precursor of miR-223 as a model, we show that 12-nt long smiRNA species are devoid of any direct mRNA regulatory activity, as assessed in a reporter gene activity assay in transfected cultured human cells. However, smiR-223 was found to modulate the ability of the microRNA from which it derives to mediate translational repression or cleavage of reporter mRNAs. Our findings suggest that the 12-nt RNA species, generated along the microRNA pathway, may participate to the control of gene expression by regulating the activity of the related full-length mature microRNA in vivo. PMID- 22675333 TI - Thermodynamic Control of Small RNA-Mediated Gene Silencing. AB - Small interfering RNAs (siRNAs) and microRNAs (miRNAs) are key regulators of posttranscriptional gene silencing, which is referred to as RNA interference (RNAi) or RNA silencing. In RNAi, siRNA loaded onto the RNA-induced silencing complex (RISC) downreugulates target gene expression by cleaving mRNA whose sequence is perfectly complementary to the siRNA guide strand. We previously showed that highly functional siRNAs possessed the following characteristics: A or U residues at nucleotide position 1 measured from the 5' terminal, four to seven A/Us in positions 1-7, and G or C residues at position 19. This finding indicated that an RNA strand with a thermodynamically unstable 5' terminal is easily retained in the RISC and functions as a guide strand. In addition, it is clear that unintended genes with complementarities only in the seed region (positions 2-8) are also downregulated by off-target effects. siRNA efficiency is mainly determined by the Watson-Crick base-pairing stability formed between the siRNA seed region and target mRNA. siRNAs with a low seed-target duplex melting temperature (T(m)) have little or no seed-dependent off-target activity. Thus, important parts of the RNA silencing machinery may be regulated by nucleotide base-pairing thermodynamic stability. A mechanistic understanding of thermodynamic control may enable an efficient target gene-specific RNAi for functional genomics and safe therapeutic applications. PMID- 22675331 TI - The secret language of destiny: stress imprinting and transgenerational origins of disease. AB - Epigenetic regulation modulates gene expression without altering the DNA sequence to facilitate rapid adjustments to dynamically changing environmental conditions. The formation of an epigenetic memory allows passing on this information to subsequent generations. Here we propose that epigenetic memories formed by adverse environmental conditions and stress represent a critical determinant of health and disease in the F3 generation and beyond. Transgenerational programming of epigenetic regulation may represent a key to understand adult-onset complex disease pathogenesis and cumulative effects of life span and familial disease etiology. Ultimately, the mechanisms of generating an epigenetic memory may become of potentially promising diagnostic and therapeutic relevance due to their reversible nature. Exploring the role of environmental factors, such as stress, in causing variations in epigenetic profiles may lead to new avenues of personalized, preventive medicine based on epigenetic signatures and interventions. PMID- 22675334 TI - Combination of the Level-Set Methods with the Contourlet Transform for the Segmentation of the IVUS Images. AB - Intravascular ultrasound (IVUS) imaging is a catheter-based medical methodology establishing itself as a useful modality for studying atherosclerosis. The detection of lumen and media-adventitia boundaries in IVUS images constitutes an essential step towards the reliable quantitative diagnosis of atherosclerosis. In this paper, a novel scheme is proposed to automatically detect lumen and media adventitia borders. This segmentation method is based on the level-set model and the contourlet multiresolution analysis. The contourlet transform decomposes the original image into low-pass components and band-pass directional bands. The circular hough transform (CHT) is adopted in low-pass bands to yield the initial lumen and media-adventitia contours. The anisotropic diffusion filtering is then used in band-pass subbands to suppress noise and preserve arterial edges. Finally, the curve evolution in the level-set functions is used to obtain final contours. The proposed method is experimentally evaluated via 20 simulated images and 30 real images from human coronary arteries. It is demonstrated that the mean distance error and the relative mean distance error have increased by 5.30 pixels and 7.45%, respectively, as compared with those of a recently traditional level set model. These results reveal that the proposed method can automatically and accurately extract two vascular boundaries. PMID- 22675335 TI - MRI in neurosciences. PMID- 22675336 TI - Cinchonine Prevents High-Fat-Diet-Induced Obesity through Downregulation of Adipogenesis and Adipose Inflammation. AB - Cinchonine (C(19)H(22)N(2)O) is a natural compound of Cinchona bark. Although cinchonine's antiplatelet effect has been reported in the previous study, antiobesity effect of cinchonine has never been studied. The main objective of this study was to investigate whether cinchonine reduces high-fat-diet- (HFD-) induced adipogenesis and inflammation in the epididymal fat tissues of mice and to explore the underlying mechanisms involved in these reductions. HFD-fed mice treated with 0.05% dietary cinchonine for 10 weeks had reduced body weight gain ( 38%), visceral fat-pad weights (-26%), and plasma levels of triglyceride, free fatty acids, total cholesterol, and glucose compared with mice fed with the HFD. Moreover, cinchonine significantly reversed HFD-induced downregulations of WNT10b and galanin-mediated signaling molecules and key adipogenic genes in the epididymal adipose tissues of mice. Cinchonine also attenuated the HFD-induced upregulation of proinflammatory cytokines by inhibiting toll-like-receptor-2- (TLR2-) and TLR4-mediated signaling cascades in the adipose tissue of mice. Our findings suggest that dietary cinchonine with its effects on adipogenesis and inflammation may have a potential benefit in preventing obesity. PMID- 22675337 TI - The Current Knowledge of the Role of PPAR in Hepatic Ischemia-Reperfusion Injury. AB - Strategies to improve the viability of steatotic livers could reduce the risk of dysfunction after surgery and increase the number of organs suitable for transplantation. Peroxisome proliferator-activated receptors (PPARs) are major regulators of lipid metabolism and inflammation. In this paper, we review the PPAR signaling pathways and present some of their lesser-known functions in liver regeneration. Potential therapies based on PPAR regulation will be discussed. The data suggest that further investigations are required to elucidate whether PPAR could be a potential therapeutic target in liver surgery and to determine the most effective therapies that selectively regulate PPAR with minor side effects. PMID- 22675338 TI - PPARalpha Activation Protects against Anti-Thy1 Nephritis by Suppressing Glomerular NF-kappaB Signaling. AB - The vast increase of chronic kidney disease (CKD) has attracted considerable attention worldwide, and the development of a novel therapeutic option against a representative kidney disease that leads to CKD, mesangial proliferative glomerulonephritis (MsPGN) would be significant. Peroxisome proliferator activated receptor alpha (PPARalpha), a member of the steroid/nuclear receptor superfamily, is known to perform various physiological functions. Recently, we reported that PPARalpha in activated mesangial cells exerted anti-inflammatory effects and that the deficiency of PPARalpha resulted in high susceptibility to glomerulonephritis. To investigate whether PPARalpha activation improves the disease activity of MsPGN, we examined the protective effects of a PPARalpha agonist, clofibrate, in a well-established model of human MsPGN, anti-Thy1 nephritis, for the first time. This study demonstrated that pretreatment with clofibrate (via a 0.02% or 0.1% clofibrate-containing diet) continuously activated the glomerular PPARalpha, which outweighed the PPARalpha deterioration associated with the nephritic process. The PPARalpha activation appeared to suppress the NF-kappaB signaling pathway in glomeruli by the induction of IkappaBalpha, resulting in the reduction of proteinuria and the amelioration of the active inflammatory pathologic glomerular changes. These findings suggest the antinephritic potential of PPARalpha-related medicines against MsPGN. PPARalpha related medicines might be useful as a treatment option for CKD. PMID- 22675339 TI - The antioxidant 3H-1,2-dithiole-3-thione potentiates advanced glycation end product-induced oxidative stress in SH-SY5Y cells. AB - Oxidative stress is implicated as a major factor in the development of diabetes complications and is caused in part by advanced glycation end products (AGEs). AGEs ligate to the receptor for AGEs (RAGE), promoting protein kinase C (PKC) dependent activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and superoxide radical generation. While scavenging antioxidants are protective against AGEs, it is unknown if induction of endogenous antioxidant defenses has the same effect. In this study, we confirmed that the compound 3H 1,2-dithiole-3-thione (D3T) increases reduced-state glutathione (GSH) concentrations and NADPH:quinone oxidoreductase 1 (NQO1) activity in SH-SY5Y cells and provides protection against H(2)O(2). Surprisingly, D3T potentiated oxidative damage caused by AGEs. In comparison to vehicle controls, D3T caused greater AGE-induced cytotoxicity and depletion of intracellular GSH levels while offering no protection against neurite degeneration or protein carbonylation. D3T potentiated AGE-induced reactive oxygen species (ROS) formation, an effect abrogated by inhibitors of PKC and NADPH oxidase. This study suggests that chemical induction of endogenous antioxidant defenses requires further examination in models of diabetes. PMID- 22675340 TI - Hepatic mitochondrial alterations and increased oxidative stress in nutritional diabetes-prone Psammomys obesus model. AB - Mitochondrial dysfunction is considered to be a pivotal component of insulin resistance and associated metabolic diseases. Psammomys obesus is a relevant model of nutritional diabetes since these adult animals exhibit a state of insulin resistance when fed a standard laboratory chow, hypercaloric for them as compared to their natural food. In this context, alterations in bioenergetics were studied. Using liver mitochondria isolated from these rats fed such a diet for 18 weeks, oxygen consumption rates, activities of respiratory complexes, and content in cytochromes were examined. Levels of malondialdehyde (MDA) and gluthatione (GSH) were measured in tissue homogenates. Diabetic Psammomys showed a serious liver deterioration (hepatic mass accretion, lipids accumulation), accompanied by an enhanced oxidative stress (MDA increased, GSH depleted). On the other hand, both ADP-dependent and uncoupled respirations greatly diminished below control values, and the respiratory flux to cytochrome oxydase was mildly lowered. Furthermore, an inhibition of complexes I and III together with an activation of complex II were found. With emergence of oxidative stress, possibly related to a defect in oxidative phosphorylation, some molecular adjustments could contribute to alleviate, at least in part, the deleterious outcomes of insulin resistance in this gerbil species. PMID- 22675341 TI - Effects of glucagon-like peptide-1 receptor agonists on body weight: a meta analysis. AB - Glucagon-Like Peptide-1 receptor agonists (GLP-1RAs), approved as glucose lowering drugs for the treatment of type 2 diabetes, have also been shown to reduce body weight. An extensive Medline, Cochrane database, and Embase search for "exenatide," "liraglutide," "albiglutide," "semaglutide," and "lixisenatide" was performed, collecting all randomized clinical trials on humans up to December 15, 2011, with a duration of at least 24 weeks, comparing GLP-1 receptor agonists with either placebo or active drugs. Twenty two (7,859 patients) and 7 (2,416 patients) trials with available results on body weight at 6 and 12 months, respectively, were included. When compared with placebo, GLP-1RAs determine a reduction of BMI at 6 months of -1.0 [-1.3; -0.6] kg/m(2). Considering the average BMI at baseline (32.4 kg/m(2)) these data means a weight reduction of about 3% at 6 months. This result could seem modest from a clinical standpoint; however, it could be affected by many factors contributing to an underestimation of the effect of GLP-1RA on body weight, such as non adequate doses, inclusion criteria, efficacy of GLP-1RA on reducing glycosuria, and association to non pharmacological interventions not specifically aimed to weight reduction. PMID- 22675342 TI - Regulation of pancreatic microRNA-7 expression. AB - Genome-encoded microRNAs (miRNAs) provide a posttranscriptional regulatory layer, which is important for pancreas development. Differentiation of endocrine cells is controlled by a network of pancreatic transcription factors including Ngn3 and NeuroD/Beta2. However, how specific miRNAs are intertwined into this transcriptional network is not well understood. Here, we characterize the regulation of microRNA-7 (miR-7) by endocrine-specific transcription factors. Our data reveal that three independent miR-7 genes are coexpressed in the pancreas. We have identified conserved blocks upstream of pre-miR-7a-2 and pre-miR-7b and demonstrated by functional assays that they possess promoter activity, which is increased by the expression of NeuroD/Beta2. These data suggest that the endocrine specificity of miR-7 expression is governed by transcriptional mechanisms and involves members of the pancreatic endocrine network of transcription factors. PMID- 22675343 TI - Frequency of genital involvement in women with oral lichen planus in southern iran. AB - Background. Lichen Planus is a chronic mucocutaneous disease of immunological basis and unknown etiology. women with oral lichen planus may have concomitant manifestations in vulvovaginal areas. Objective. To determine the frequency and risk factors of genital involvement in a group of Iranian women affected by oral lichen planus. Methods. Thirty-six women with clinical and histopathological diagnosis of oral lichen planus were evaluated for demographic, historical, and clinical parameters of the oral disease. All the patients were referred for careful vulvovaginal examination, as well as histopathological assessment upon clinical indication. Results. Nineteen patients complained from genital symptoms but the number of women with the final diagnosis of genital lichen planus (n = 2) was too small to show any correlation with the parameters evaluated. Conclusion. In spite of low genital involvement possibly due to inadequate patient population, lack of follow-up visits, and contribution of genetic or ethnic factors, for conservative patient care, women with the oral lichen planus in particular those having some relevant genital symptoms, should preferably be referred for careful vulvovaginal examination. Multicenter cohort studies on women of different geographical regions or ethnicities who have genital lichen planus alone or in combination with other common sites are encouraged. PMID- 22675344 TI - Effects of cosmetic formulations containing hydroxyacids on sun-exposed skin: current applications and future developments. AB - This paper describes recent data on the effects of various skin formulations containing hydroxyacids (HAs) and related products on sun-exposed skin. The most frequently used classes of these products, such as alpha- and beta-hydroxyacids, polyhydroxy acids, and bionic acids, are reviewed, and their application in cosmetic formulations is described. Special emphasis is devoted to the safety evaluation of these formulations, particularly on the effects of their prolonged use on sun-exposed skin. We also discuss the important contribution of cosmetic vehicles in these types of studies. Data on the effects of HAs on melanogenesis and tanning are also included. Up-to-date methods and techniques used in those explorations, as well as selected future developments in the cosmetic area, are presented. PMID- 22675345 TI - Controversies in the treatment of ingrown nails. AB - Ingrown toenails are one of the most frequent nail disorders of young persons. They may negatively influence daily activities, cause discomfort and pain. Since more than 1000 years, many different treatments have been proposed. Today, conservative and surgical methods are available, which, when carried out with expertise, are able to cure the disease. Packing, taping, gutter treatment, and nail braces are options for relatively mild cases whereas surgery is exclusively done by physicians. Phenolisation of the lateral matrix horn is now the safest, simplest, and most commonly performed method with the lowest recurrence rate. Wedge excisions can no longer be recommended. PMID- 22675346 TI - Minor salivary gland tumours of upper aerodigestive tract: a clinicopathological study. AB - The aim of this retrospective study of 56 patients with minor salivary gland tumours (MSGTs) of the upper aerodigestive tract is to present demographic features, distribution of tumours as well as methods and results of treatment performed in our institution over a 10-year period. Of 221 patients with salivary gland tumours, 56 patients with MSGT were selected. There were 36 female and 20 male patients aged from 8 to 81 years. Male-to-female ratio was 1 : 2 in the group of benign MSGT and 1 : 1.7 in the group of malignant tumours. The palate was the most frequent site of MSGT (45.6%), followed by buccal mucosa (19.3%). Of all MSGTs 63.2% were malignant, and 36.8% were benign. Adenoid cystic carcinoma was the most common neoplasm (31.6%), followed by pleomorphic adenoma (29.8%). Surgery was the method of choice in the treatment of patients with MSGT. Postoperative defects were reconstructed by prosthetic obturators, local flaps, and free radial forearm flap. Relative survival for patients with malignant MSGT was 88% at three years and 71.5% at five years. MSGTs are more frequent in females and predominantly affect the palate. Malignant MSGTs are more common than benign. PMID- 22675347 TI - Management of Localized Prostate Cancer by Focal Transurethral Resection of Prostate Cancer: An Application of Radical TUR-PCa to Focal Therapy. AB - Background. We analyzed radical TUR-PCa against localized prostate cancer. Patients and Methods. Seventy-nine out of 209 patients with prostate cancer in one lobe were studied. Patients' age ranged from 58 to 91 years and preoperative PSA, 0.70 to 17.30 ng/mL. In other 16 additional patients we performed focal TUR PCa. Patients' age ranged from 51 to 87 years and preoperative PSA, 1.51 to 25.74 ng/mL. Results. PSA failure in radical TUR-PCa was 5.1% during the mean follow-up period of 58.9 months. The actuarial biochemical non-recurrence rate was 98.2% for pT2a and 90.5% for pT2b. Bladder neck contracture occurred in 28 patients (35.4%). In 209 patients, pathological study revealed prostate cancer of the peripheral zone near the neurovascular bundle bilaterally in 25%, unilaterally in 39% and no cancer bilaterally in 35%, suggesting the possibility of focal TUR PCa. Postoperative PSA of 16 patients treated by focal TUR-PCa was stable between 0.007 and 0.406 ng/mL at 24.2 months' follow-up. No patients suffered from urinary incontinence. Bladder neck contracture developed in only 1 patient and all 5 patients underwent nerve-preserving TUR-PCa did not show erectile dysfunction. Conclusion. Focal TUR-PCa was considered to be a promising option among focal therapies against localized prostate cancer. PMID- 22675348 TI - BRASERO: A Resource for Benchmarking RNA Secondary Structure Comparison Algorithms. AB - The pairwise comparison of RNA secondary structures is a fundamental problem, with direct application in mining databases for annotating putative noncoding RNA candidates in newly sequenced genomes. An increasing number of software tools are available for comparing RNA secondary structures, based on different models (such as ordered trees or forests, arc annotated sequences, and multilevel trees) and computational principles (edit distance, alignment). We describe here the website BRASERO that offers tools for evaluating such software tools on real and synthetic datasets. PMID- 22675350 TI - Psychological status and quality of life in relation to the metabolic syndrome: Isfahan Cohort Study. AB - OBJECTIVE: Current study was designed to investigate the association of metabolic syndrome (MetS) with depression, anxiety, psychological distress, and quality of life (QoL). DESIGN: Two hundred and fifteen contributors with MetS and 253 participants without MetS were randomly selected from 2151 participants of Isfahan Cohort Study who were residents of Isfahan city. Measurements consisted of fasting blood samples, anthropometrics, and self-reported data of 12-item General Health Questionnaire, Hospital Anxiety and Depression Scale, and European Quality of Life-5 Dimension. Binary logistic regression analysis was used to find the association between MetS and four psychological factors. RESULTS: Participants mean age was 56.3 +/- 9.8 years. Male/female ratio was 0.86 (217/251). Mean score of depression (P = 0.003), anxiety (P = 0.018), distress (P = 0.047), and QoL (P <= 0.001) was significantly higher in MetS group. There were significant increasing relationships between depression (OR 1.10, 95% CI 1.03 1.22), anxiety (OR 1.03, 95% CI 1.05-1.11), and QoL (OR 1.13, 95% CI 1.05-1.23) and MetS when associations were adjusted for other risk factors, but it was not the case for distress (OR 1.03, 95% CI 0.99-1.08). CONCLUSION: It might be better to consider MetS as a combination of biological and psychological risk factors. Thus, a person with metabolic disease should be recognized as a patient with these factors and be screened for all of them. PMID- 22675349 TI - Pancreatic function, type 2 diabetes, and metabolism in aging. AB - Aging is a risk factor for impaired glucose tolerance and diabetes. Of the reported 25.8 million Americans estimated to have diabetes, 26.9% are over the age of 65. In certain ethnic groups, the proportion is even higher; almost 1 in 3 older Hispanics and African Americans and 3 out of 4 Pima Indian elders have diabetes. As per the NHANES III (Third National Health and Nutrition Examination) survey, the percentage of physician-diagnosed diabetes increased from 3.9% in middle-aged adults (40-49 years) to 13.2% in elderly adults (>=75 years). The higher incidence of diabetes is especially alarming considering that diabetes in itself increases the risk for multiple other age-related diseases such as cancer, stroke, cardiovascular diseases, Parkinson's disease, and Alzheimer's disease (AD). In this review, we summarize the current evidence on how aging affects pancreatic beta cell function, beta cell mass, insulin secretion and insulin sensitivity. We also review the effects of aging on the relationship between insulin sensitivity and insulin secretion. Understanding the mechanisms that lead to impaired glucose homeostasis and T2D in the elderly will lead to development of novel treatments that will prevent or delay diabetes, substantially improve quality of life and ultimately increase overall life span. PMID- 22675351 TI - Determination of thyroid volume by ultrasonography among schoolchildren in Philippines. AB - OBJECTIVE: Iodine deficiency is defined by the goiter and the urinary iodine concentration. However, a lack of local thyroid volume reference data resulted in the vague definition of goiter, especially in school-aged children. The aim of this paper was to determine the thyroid volumes by ultrasonography in schoolchildren aged 6 to 12 years living in Cagayan areas in Philippine. METHODS: Cross-sectional thyroid ultrasonographic data of 158 schoolchildren aged 6-12 years from Tuguegarao and Lagum in Cagayan valley, Philippine were used. Thyroid volumes were compared based on logistic issue and urban and rural area and compared with other previously reported data. RESULTS: The mean values of thyroid volume in Tuguerago and Lagum were 2.99 +/- 1.34 mL and 2.42 +/- 0.92 mL. The thyroid size was significantly in association with age (P < 0.00), weight (P < 0.00), height (P < 0.00), and BSA (P < 0.00) by Pearson's correlation. The median thyroid volumes of schoolchildren investigated in this study were generally low compared to international reference data by age group but not by BSA. CONCLUSIONS: We propose for the first time local reference ultrasound values for thyroid volumes in 6-12 aged schoolchildren that should be used for monitoring iodine deficiency disorders. PMID- 22675352 TI - Distribution of urocortins and corticotropin-releasing factor receptors in the cardiovascular system. AB - Urocortins are human homologues of urotensin I, a fish corticotropin-releasing factor- (CRF-) like peptide secreted from the urophysis. There are three urocortins: urocortin 1, urocortin 2, and urocortin 3 in mammals. We have shown that urocortin 1 and urocortin 3 are endogenously synthesized in the myocardial cells of human heart and may act on CRF type 2 receptor (CRFR2) expressed in the heart. Expression levels of urocortin 1 in the heart and plasma urocortin 1 levels are elevated in patients with heart failure. Recent studies have shown that urocortins have various biological actions in the cardiovascular system, such as a vasodilator action, a positive inotropic action, a cardioprotective action against ischemia/reperfusion injury, and suppressive actions against the renin angiotensin system and the sympathetic nervous system. Urocortins and CRFR2 may therefore be a potential therapeutic target for cardiovascular diseases, such as congestive heart failure, hypertension, and myocardial infarction. PMID- 22675353 TI - Tolerance-inducing strategies in islet transplantation. AB - Allogeneic islet transplantation is a promising approach for restoring normoglycemia in type 1 diabetic patients. Current use of immunosuppressive therapies for management of islet transplant recipients can be counterintuitive to islet function and can lead to complications in the long term. The induction of donor-specific tolerance eliminates the dependency on immunosuppression and allows recipients to retain responses to foreign antigens. The mechanisms by which tolerance is achieved involve the deletion of donor-reactive T cells, induction of T-cell anergy, immune deviation, and generation of regulatory T cells. This review will outline the various methods used for inducing donor specific tolerance in islet transplantation and will highlight the previously unforeseen potential of tissue stromal cells in promoting islet engraftment. PMID- 22675354 TI - Gestational diabetes mellitus: a positive predictor of type 2 diabetes? AB - The aim of this paper is to consider the relative benefits of screening for type two diabetes mellitus in women with a previous pregnancy complicated by gestational diabetes mellitus. Recent studies suggest that women who experience GDM are at a greater risk of developing type 2 diabetes within 10-20 years of their index pregnancy. If considered as a stand-alone indicator of the risk of developing type 2 diabetes, GDM is a poor diagnostic test. Most women do not develop GDM during pregnancy and of those that do most do not develop type 2 diabetes. There is, however, a clear need for better early detection of predisposition to disease and/or disease onset to significantly impact on this global pandemic. The putative benefits of multivariate approaches and first trimester and preconception screening to increase the sensitivity of risk assignment modalities for type 2 diabetes are proposed. PMID- 22675356 TI - Effect of intra-orifice depth on sealing ability of four materials in the orifices of root-filled teeth: an ex-vivo study. AB - Aim. To investigate the effect of orifice cavity depth on the sealing ability of Fusio, Fuji II, Fuji IX, and MTA"G". Materials and Methods. Ninety-two canals in extracted mandibular premolars were prepared, obturated, and randomly grouped into 4 groups. Each group was subgrouped for a 2 mm and 3 mm orifice cavity depth (n = 10). The remaining roots were divided to serve as positive and negative controls (n = 6). Cavities of the 4 experimental groups were filled with the respective materials and subjected to methylene blue dye leakage. Linear leakage was measured in mm using a stereomicroscope. Statistical Analysis. Kruskall Wallis test was used at P < 0.05, and t-test was done to compare 2 mm and 3 mm. Results. All tested materials leaked to various degrees. Significantly higher leakage score was found for Fuji IX, Fusio, Fuji II, and MTA "G" in a descending order, when the materials were placed at 3 mm depths. A significant difference was found in the leakage score between the 2 mm and 3 mm depths in all tested materials with the 3 mm depth showing a greater leakage score in all tested materials. Exception was in MTA "G" at 2 mm and 3 mm depths (0.551 mm +/- 0.004 mm and 0.308 mm +/- 0.08 mm, resp.). Conclusion. The null hypothesis should be partially rejected. Fusio and MTA "G" were affected by orifice cavity depth with regard to their sealing ability. MTA "G" had the least leakage when placed at 2 or 3 mm depths, and Fusio is the next when placed at 2 mm depth. Two millimeters orifice cavity depth is suitable for most adhesive orifice barrier materials. PMID- 22675355 TI - Ectopic fat and insulin resistance: pathophysiology and effect of diet and lifestyle interventions. AB - The storage of triglyceride (TG) droplets in nonadipose tissues is called ectopic fat storage. Ectopic fat is associated with insulin resistance and type 2 diabetes mellitus (T2DM). Not the triglycerides per se but the accumulation of intermediates of lipid metabolism in organs, such as the liver, skeletal muscle, and heart seem to disrupt metabolic processes and impair organ function. We describe the mechanisms of ectopic fat depositions in the liver, skeletal muscle, and in and around the heart and the consequences for each organs function. In addition, we systematically reviewed the literature for the effects of diet induced weight loss and exercise on ectopic fat depositions. PMID- 22675357 TI - The effect of alternating current iontophoresis on rats with the chronic constriction injury to the infraorbital nerve. AB - This study aimed to examine the effect of AC iontophoresis on rats with the chronic constriction injury (CCI) to the infraorbital nerve by animal experiments. CCI model rats were divided into four groups, namely, rats that received general anesthesia for 60 min except AC IOP (CCI: n = 5), AC IOP with 0.9% physiological saline for 60 min (CCI + saline AC IOP: n = 5), AC IOP with 4% lidocaine hydrochloride for 60 min (CCI + lidocaine AC IOP: n = 5), and attachment of two electrodes soaked with 4% lidocaine hydrochloride to the facial skin for 60 min (CCI + attach lidocaine: n = 5). In the CCI + lidocaine AC IOP group, an elevated withdrawal threshold was observed after AC IOP, and the duration of efficacy was longer compared with that in the CCI + saline AC IOP and CCI + attached lidocaine groups. A significant decrease in the number of Fos-like immunoreactive (LI) cells was observed in the CCI + lidocaine AC IOP group compared with that in the CCI group. These findings suggest that the effect of CCI + lidocaine AC IOP group may be caused by active permeation of lidocaine into the facial skin and electrical stimulation of the trigeminal nucleus. PMID- 22675358 TI - An in vitro evaluation of leakage of two etch and rinse and two self-etch adhesives after thermocycling. AB - Our experiment evaluated the microleakage in resin composite restorations bonded to dental tissues with different adhesive systems. 40 class V cavities were prepared on the facial and lingual surfaces of each tooth with coronal margins in enamel and apical margins in cementum (root dentin). The teeth were restored with Z100 resin composite bonded with different adhesive systems: Scotchbond Multipurpose (SBMP), a 3-step Etch and Rinse adhesive, Adper Scotchbond 1 XT (SB1), a 2-step Etch and Rinse adhesive, AdheSE One (ADSE-1), a 1-step Self-Etch adhesive, and AdheSE (ADSE), a 2-step Self-Etch adhesive. Teeth were thermocycled and immersed in 50% silver nitrate solution. When both interfaces were considered, SBMP has exhibited significantly less microleakage than other adhesive systems (resp., for SB1, ADSE-1 and ADSE, P = 0.0007, P < 0.0001 and P < 0.0001). When enamel and dentin interfaces were evaluated separately, (1) for the Self-Etch adhesives, microleakage was found greater at enamel than at dentin interfaces (for ADSE, P = 0.024 and for ADSE-1, P < 0.0001); (2) for the Etch and Rinse adhesive systems, there was no significant difference between enamel and dentin interfaces; (3) SBMP was found significantly better than other adhesives both at enamel and dentin interfaces. In our experiment Etch and Rinse adhesives remain better than Self-Etch adhesives at enamel interface. In addition, there was no statistical difference between 1-step (ADSE-1) and 2-step (ADSE) Self-Etch adhesives. PMID- 22675359 TI - MC3T3-E1 Cells on Titanium Surfaces with Nanometer Smoothness and Fibronectin Immobilization. AB - The present study was aimed to evaluate the viability and total protein contents of osteoblast-like cells on the titanium surface with different surface mechanical treatment, namely, nanometer smoothing (Ra: approximately 2.0 nm) and sandblasting (Ra: approximately 1.0 MUm), and biochemical treatment, namely, with or without fibronectin immobilization. Fibronectin could be easily immobilized by tresyl chloride-activation technique. MC3T3-E1 cells were seeded on the different titanium surfaces. Cell viability was determined by MTT assay. At 1 day of cell culture, there were no significant differences in cell viability among four different titanium surfaces. At 11 days, sandblasted titanium surface with fibronectin immobilization showed the significantly highest cell viability than other titanium surface. No significant differences existed for total protein contents among four different titanium surfaces at 11 days of cell culture. Scanning electron microscopy observation revealed that smoothness of titanium surface produced more spread cell morphologies, but that fibronectin immobilization did not cause any changes of the morphologies of attached cells. Fibronectin immobilization provided greater amount of the number of attached cells and better arrangement of attached cells. In conclusion, the combination of sandblasting and fibronectin immobilization enhanced the cell viability and fibronectin immobilization providing better arrangements of attached cells. PMID- 22675360 TI - The Role of Mitochondrial NADPH-Dependent Isocitrate Dehydrogenase in Cancer Cells. AB - Isocitrate dehydrogenase 2 (IDH2) is located in the mitochondrial matrix. IDH2 acts in the forward Krebs cycle as an NADP(+)-consuming enzyme, providing NADPH for maintenance of the reduced glutathione and peroxiredoxin systems and for self maintenance by reactivation of cystine-inactivated IDH2 by glutaredoxin 2. In highly respiring cells, the resulting NAD(+) accumulation then induces sirtuin-3 mediated activating IDH2 deacetylation, thus increasing its protective function. Reductive carboxylation of 2-oxoglutarate by IDH2 (in the reverse Krebs cycle direction), which consumes NADPH, may follow glutaminolysis of glutamine to 2 oxoglutarate in cancer cells. When the reverse aconitase reaction and citrate efflux are added, this overall "anoxic" glutaminolysis mode may help highly malignant tumors survive aglycemia during hypoxia. Intermittent glycolysis would hypothetically be required to provide ATP. When oxidative phosphorylation is dormant, this mode causes substantial oxidative stress. Arg172 mutants of human IDH2-frequently found with similar mutants of cytosolic IDH1 in grade 2 and 3 gliomas, secondary glioblastomas, and acute myeloid leukemia-catalyze reductive carboxylation of 2-oxoglutarate and reduction to D-2-hydroxyglutarate, which strengthens the neoplastic phenotype by competitive inhibition of histone demethylation and 5-methylcytosine hydroxylation, leading to genome-wide histone and DNA methylation alternations. D-2-hydroxyglutarate also interferes with proline hydroxylation and thus may stabilize hypoxia-induced factor alpha. PMID- 22675361 TI - Mitochondrial Stress Signalling: HTRA2 and Parkinson's Disease. AB - Mitochondria are cellular energy generators whose activity requires a continuous supply of oxygen. Recent genetic analysis has suggested that defects in mitochondrial quality control may be key factors in the development of Parkinson's disease (PD). Mitochondria have a crucial role in supplying energy to the brain, and their deterioration can affect the function and viability of neurons, contributing to neurodegeneration. These organelles can sow the seeds of their own demise because they generate damaging oxygen-free radicals as a byproduct of their intrinsic physiological functions. Mitochondria have therefore evolved specific molecular quality control mechanisms to compensate for the action of damaging agents such as oxygen-free radicals. PTEN-induced putative kinase 1 (PINK1) and high-temperature-regulated A2 (HTRA2), a mitochondrial protease, have recently been proposed to be key modulators of mitochondrial molecular quality control. Here, we review some of the most recent advances in our understanding of mitochondria stress-control pathways, focusing on how signalling by the p38 stress kinase pathway may regulate mitochondrial stress by modulating the activity of HTRA2 via PINK1 and cyclin-dependent kinase 5 (CDK5). We also propose how defects in this pathway may contribute to PD. PMID- 22675364 TI - The influence of partial knee replacement designs on tensile strain at implant bone interface. AB - Partial knee replacement (PKR) results in fast recovery and good knee mechanics and is ideal to treat medial knee osteoarthritis. Cementless PKR depends on bone growing into the implant surface for long-term fixation. Implant loosening may occur due to high tensile strain resulted from large mechanical loads during rehab exercises. The purpose of this study is to investigate whether external fixations such as superior screw and frontal flange could reduce the tensile strain at the implant-bone interface. Three medial PKRs were designed. The first PKR had no external fixations. A superior screw and a frontal flange were then added to the first PKR to form the second and third PKR designs, respectively. Finite element analysis was performed to examine the tensile strain at the implant-bone interface during weight-bearing exercises. The PKR with no external fixations exhibited high tensile strain at the anterior implant-bone interface. Both the screwed and flanged PKRs effectively reduced the tensile strain at the anterior implant-bone interface. Furthermore, the flanged PKR resulted in a more uniform reduction of the tensile strain than the screwed PKR. In conclusion, external fixations are necessary to alleviate tensile strain at the implant-bone interface during knee rehab exercises. PMID- 22675362 TI - Altered gene expression, mitochondrial damage and oxidative stress: converging routes in motor neuron degeneration. AB - Motor neuron diseases (MNDs) are a rather heterogeneous group of diseases, with either sporadic or genetic origin or both, all characterized by the progressive degeneration of motor neurons. At the cellular level, MNDs share features such as protein misfolding and aggregation, mitochondrial damage and energy deficit, and excitotoxicity and calcium mishandling. This is particularly well demonstrated in ALS, where both sporadic and familial forms share the same symptoms and pathological phenotype, with a prominent role for mitochondrial damage and resulting oxidative stress. Based on recent data, however, altered control of gene expression seems to be a most relevant, and previously overlooked, player in MNDs. Here we discuss which may be the links that make pathways apparently as different as altered gene expression, mitochondrial damage, and oxidative stress converge to generate a similar motoneuron-toxic phenotype. PMID- 22675363 TI - GSK-3beta: A Bifunctional Role in Cell Death Pathways. AB - Although glycogen synthase kinase-3 beta (GSK-3beta) was originally named for its ability to phosphorylate glycogen synthase and regulate glucose metabolism, this multifunctional kinase is presently known to be a key regulator of a wide range of cellular functions. GSK-3beta is involved in modulating a variety of functions including cell signaling, growth metabolism, and various transcription factors that determine the survival or death of the organism. Secondary to the role of GSK-3beta in various diseases including Alzheimer's disease, inflammation, diabetes, and cancer, small molecule inhibitors of GSK-3beta are gaining significant attention. This paper is primarily focused on addressing the bifunctional or conflicting roles of GSK-3beta in both the promotion of cell survival and of apoptosis. GSK-3beta has emerged as an important molecular target for drug development. PMID- 22675366 TI - Benign cystic mesothelioma: a rare cause for scrotal swelling. AB - Benign cystic mesothelioma of the tunica vaginalis is a rare occurrence. It usually presents with painless gradual swelling in the scrotum. These types of benign mesotheliomas typically occur in the peritoneum and usually affect young to middle-aged patients. We present in this case an unusual case of benign cystic mesothelioma of the tunica vaginalis in a 77-year-old male patient. PMID- 22675365 TI - Phytoestrogens in human pregnancy. AB - Background. The hormonal milieu associated with pregnancy has become a focus of interest owing to potential links with the developmental origins of health and disease. Phytoestrogens are hormonally active plant-derived chemicals that may have an impact on human reproductive processes. However, developmental exposure to phytoestrogens has not been well characterized and thus our objective was to quantify phytoestrogen exposure during pregnancy and lactation. Methods. Women in the second trimester of pregnancy entered the study during counseling for prenatal genetic information. Women who had an indication for a genetic amniocentesis on the basis of late maternal age were approached for inclusion. They completed an environmental questionnaire; a sample of amniotic fluid was collected for karyotype, blood was collected from women during pregnancy and at birth, from the umbilical cord and breast milk. Samples were tested for the presence of daidzein and genistein by GC Mass Spectroscopy. Findings. Phytoestrogens are commonly found in pregnant women's serum and amniotic fluid during pregnancy. There is a sex difference in the concentrations with higher levels in amniotic fluid containing female fetuses. This difference was not present in maternal serum. Soy ingestion increases amniotic fluid phytoestrogen concentrations in female and male fetuses. The presence and concentrations of phytoestrogens did not differ in relation to common pregnancy complications or preexisting infertility. PMID- 22675367 TI - Ulcerative Necrobiosis Lipoidica: Is There a Place for Anti-TNFalpha Treatment? AB - Necrobiosis lipoidica is a rare granulomatous and inflammatory disease. Its management is particularly difficult when ulceration is present. The authors describe the clinical case of a 65-year-old female patient with necrobiosis lipoidica, who had been submitted in the past to several topical and systemic treatments with little or no improvement. She started treatment with subcutaneous etanercept and showed significant improvement without adverse events until today. The aim of this article is to report a valid and efficient alternative treatment to recalcitrant cases. PMID- 22675368 TI - Oral feeding competences of healthy preterm infants: a review. AB - Background. With increasing sophistication and technology, survival rates hugely improved among preterm infants admitted to the neonatal intensive care unit. Nutrition and feeding remain a challenge and preterm infants are at high risk of encountering oral feeding difficulties. Objective. To determine what facts may impact on oral feeding readiness and competence and which kind of interventions should enhance oral feeding performance in preterm infants. Search Strategy. MEDILINE database was explored and articles relevant to this topic were collected starting from 2009 up to 2011. Main Results. Increasingly robust alertness prior to and during feeding does positively impact the infant's feeding Skills. The review found that oral and non-oral sensorimotor interventions, provided singly or in combination, shortened the transition time to independent oral feeding in preterm infants and that preterm infants who received a combined oral and sensorimotor intervention demonstrated more advanced nutritive sucking, suck swallow and swallow-respiration coordination than those who received an oral or sensorimotor intervention singly. PMID- 22675370 TI - Beyond the Immune System: The Role of Resident Cells in Asthma and COPD. PMID- 22675371 TI - Incorporating environmental health in clinical medicine. PMID- 22675369 TI - Antimicrobial peptides as infection imaging agents: better than radiolabeled antibiotics. AB - Nuclear medicine imaging techniques offer whole body imaging for localization of number and site of infective foci inspite of limitation of spatial resolution. The innate human immune system contains a large member of important elements including antimicrobial peptides to combat any form of infection. However, development of antibiotics against bacteria progressed rapidly and gained popularity over antimicrobial peptides but even powerful antimicrobials failed to reduce morbidity and mortality due to emergence of mutant strains of bacteria resulting in antimicrobial resistance. Differentiation between infection and inflammation using radiolabeled compounds with nuclear medicine techniques has always been a dilemma which is still to be resolved. Starting from nonspecific tracers to specific radiolabeled tracers, the question is still unanswered. Specific radiolabeled tracers included antibiotics and antimicrobial peptides which bind directly to the bacteria for efficient localization with advanced nuclear medicine equipments. However, there are merits and demerits attributed to each. In the current paper, radiolabeled antibiotics and radiolabeled peptides for infection localization have been discussed starting with the background of primitive nonspecific tracers. Radiolabeled antimicrobial peptides have certain merits compared with labeled antibiotics which make them superior agents for localization of infective focus. PMID- 22675372 TI - Risk and protective factors for breast cancer in Midwest of Brazil. AB - Patterns of physical activity, body composition, and breastfeeding are closely related to health and are influenced by environmental, economic, and social factors. With the increase of sedentary lifestyle and overweight, many chronic diseases have also increased, including cancer. Breast cancer is the most common cancer in women worldwide, and the knowledge of its risk and protective factors is important to the adoption of primary prevention strategies. We aimed to investigate some risk and protective factors for breast cancer among women from Midwest Brazil. It is a case-control study of outpatient basis, carried out with 93 breast cancer cases and 186 controls. Socioeconomic, gynecological, anthropometric, and lifestyle variables were collected, and odds ratios (ORs) values were estimated (significance level, 5%; confidence interval (CI), 95%). Per capita income equal to or lower than 1/2 Brazilian minimum wage (OR = 1.88; CI = 1.06-3.29), residence in rural area (OR = 4.93; CI = 1.65-14.73), and presence of family history of breast cancer (OR = 5.38; CI = 1.46-19.93) are risk factors for breast cancer. In turn, physical activity (past 6 months) (OR = 0.23; CI = 0.10-0.55) and leisure physical activity at 20 years old (OR = 0.13; CI = 0.03-0.54) are protective factors for the disease in women who live in Midwest of Brazil. PMID- 22675373 TI - Heterogeneity in past year cigarette smoking quit attempts among Latinos. AB - OBJECTIVE: Examine the association between English language proficiency (ELP) and immigrant generation and having made a cigarette smoking quit attempt in the past 12 months among Latinos. Examine if gender moderates the association between acculturation and quit attempts. METHODS: Latino past year smokers from the 2003 and 2006/07 Tobacco Use Supplement to the Current Population Survey were analyzed. Logistic regression was used to examine the association between quit attempt and ELP and immigrant generation, controlling for demographics and smoking characteristics. RESULTS: Latinos with poor ELP were more likely to have made a quit attempt compared to those with good ELP (adjusted odds ratio [AOR] = 1.22, confidence interval [CI]: 1.02-1.46) after controlling for demographic and smoking characteristics. First (AOR = 1.21, CI: 1.02-1.43) and second generation immigrants (AOR = 1.36, CI: 1.12-1.64) were more likely than third generation immigrants to have made a quit attempt in the past 12 months. CONCLUSION: Quit behaviors are shaped by differences in language ability and generational status among Latinos. This underscores the need to disaggregate Latinos beyond racial/ethnic categories to identify subgroup differences relevant for smoking and smoking cessation behaviors in this population. PMID- 22675376 TI - Chinese medicine injection qingkailing for treatment of acute ischemia stroke: a systematic review of randomized controlled trials. AB - Qingkailing (QKL) injection was a famous traditional Chinese patent medicine, which was extensively used to treat the acute stages of cerebrovascular disease. The aim of this study was to assess the quantity, quality and overall strength of the evidence on QKL in the treatment of acute ischemic stroke. Methods. An extensive search was performed within MEDLINE, Cochrane, CNKI, Vip and Wan-Fang up to November 2011. Randomized controlled trails (RCTs) on QKL for treatment of acute stroke were collected, irrespective of languages. Study selection, data extraction, quality assessment, and data analyses were conducted according to the Cochrane standards, and RevMan5 was used for data analysis. Results. 7 RCTs (545 patients) were included and the methodological quality was evaluated as generally low. The pooled results showed that QKL combined with conventional treatment was more effective in effect rate, and the score of MESSS and TNF-alpha level compared with conventional treatment alone, but there was no significant difference in mortality of two groups. Only one trial reported routine life status. There were four trials reported adverse events, and no obvious adverse event occurred in three trials while one reported adverse events described as eruption and dizziness. PMID- 22675374 TI - Pilot study results from a brief intervention to create smoke-free homes. AB - Very few community-based intervention studies have examined how to effectively increase the adoption of smoke-free homes. A pilot study was conducted to test the feasibility, acceptability, and short-term outcomes of a brief, four component intervention for promoting smoke-free home policies among low-income households. We recruited forty participants (20 smokers and 20 nonsmokers) to receive the intervention at two-week intervals. The design was a pretest-posttest with follow-up at two weeks after intervention. The primary outcome measure was self-reported presence of a total home smoking ban. At follow-up, 78% of participants reported having tried to establish a smoke-free rule in their home, with significantly more nonsmokers attempting a smoke-free home than smokers (P = .03). These attempts led to increased smoking restrictions, that is, going from no ban to a partial or total ban, or from a partial to a total ban, in 43% of the homes. At follow-up, 33% of the participants reported having made their home totally smoke-free. Additionally, smokers reported smoking fewer cigarettes per day. Results suggest that the intervention is promising and warrants a rigorous efficacy trial. PMID- 22675377 TI - Cyprinus carpio Decoction Improves Nutrition and Immunity and Reduces Proteinuria through Nephrin and CD2AP Expressions in Rats with Adriamycin-Induced Nephropathy. AB - Cyprinus carpio decoction (CCD) is a well-known Chinese food medicine formula, accepted widely as a useful therapy in preventing edema and proteinuria caused by renal disease. However, the mechanism underlying this effect remains unclear. The current study investigated the potential mechanism of CCD in alleviating nephropathy induced by adriamycin (ADR) in rats. 70 eight-week-old Wistar rats were randomly divided into normal, model, fosinopril, YD, YG groups. All rats except for the normal group received 6.5 mg/kg.bw of ADR injection into the vena caudalis once. Different doses of CCD (11.3 and 22.5 g kg(-1)) were lavaged to rats in YD and YG groups, respectively. Then the serum biochemical values of the total protein (TP), albumin (ALB), blood urea nitrogen (BUN), creatinine (Cr), electrolyte levels, and the urinary protein (UP) content in 12 hr urine were measured. Interleukin-4 (IL-4) and interferon (INF-gamma) were measured by enzyme like immunosorbent assay (ELISA). The pathomorphological analysis was observed using light and electron microscopy, and the expressions of nephrin and CD2 associated protein (CD2AP) in renal tissues were determined by immunohistochemical assay. The results indicated that CCD can relieve ADR-induced nephropathy (ADN) by improving the nutrition status, regulating the immunity, and inhibiting proteinuria by increasing nephrin and CD2AP expressions. PMID- 22675378 TI - Applications of New Technologies and New Methods in ZHENG Differentiation. AB - With the hope to provide an effective approach for personalized diagnosis and treatment clinically, Traditional Chinese Medicine (TCM) is being paid increasing attention as a complementary and alternative medicine. It performs treatment based on ZHENG (TCM syndrome) differentiation, which could be identified as clinical special phenotypes by symptoms and signs of patients. However, it caused skepticism and criticism because ZHENG classification only depends on observation, knowledge, and clinical experience of TCM practitioners, which is lack of objectivity and repeatability. Scientists have done fruitful researches for its objectivity and standardization. Compared with traditional four diagnostic methods (looking, listening and smelling, asking, and touching), in this paper, the applications of new technologies and new methods on the ZHENG differentiation were systemically reviewed, including acquisition, analysis, and integration of clinical data or information. Furthermore, the characteristics and application range of these technologies and methods were summarized. It will provide reference for further researches. PMID- 22675379 TI - Antifungal activity of maytenin and pristimerin. AB - Fungal infections in humans have increased alarmingly in recent years, particularly in immunocompromised individuals. Among the infections systemic candidiasis, aspergillosis, cryptococcosis, paracoccidioidomycosis, and histoplasmosis mortality are more prevalent and more severe in humans. The current high incidence of dermatophytosis is in humans, especially as the main etiologic agents Trichophyton rubrum and Trichophyton mentagrophytes. Molecules pristimerin and maytenin obtained from the plant Maytenus ilicifolia (Celastraceae) are known to show various pharmacological activities. This study aimed to evaluate the spectrum of antifungal activity of maytenin and pristimerin and their cytotoxicity in human keratinocytes (NOK cells of the oral mucosa). It was concluded that the best spectrum of antifungal activity has been shown to maytenin with MIC varying from 0.12 to 125 mg/L, although it is also active with pristimerin MIC ranging between 0.12 and 250 mg/L. Regarding the toxicity, both showed to have high IC(50). The SI showed high pristimerin against some species of fungi, but SI maytenin was above 1.0 for all fungi tested, showing a selective action of fungi. However, when comparing the two substances, maytenin also showed better results. The two molecules can be a possible prototype with a broad spectrum of action for the development of new antifungal agents. PMID- 22675380 TI - Effect of keishibukuryogan on endothelial function in patients with at least one component of the diagnostic criteria for metabolic syndrome: a controlled clinical trial with crossover design. AB - We evaluated the effect of keishibukuryogan (KBG; Guizhi-Fuling-Wan), a traditional Japanese (Kampo) formula, on endothelial function assessed by reactive hyperemia peripheral arterial tonometry (Endo-PAT2000) in patients with metabolic syndrome-related factors by controlled clinical trial with crossover design. Ninety-two patients were assigned to group A (first KBG-treatment period, then control period; each lasting 4 weeks, with about one-year interval) or group B (first control, then KBG-treatment). In forty-nine (27, group A; 22, group B) patients completing all tests, the mean value of the natural logarithmic-scaled reactive hyperemia index (L_RHI) increased and those of serum nonesterified fatty acid (NEFA), malondialdehyde, and soluble vascular cell adhesion molecule 1 decreased significantly during the KBG-treatment period, but not during the control period, and 4-week changes of L_RHI, NEFA, and malondialdehyde between the 2 periods showed significance. These results suggest that KBG has beneficial effect on endothelial function in patients with metabolic syndrome-related factors. PMID- 22675381 TI - The Immunomodulatory Effect of You-Gui-Wan on Dermatogoides-pteronyssinus-Induced Asthma. AB - The traditional Chinese medicine You-Gui-Wan (YGW) contains ten species of medicinal plants and has been used to improve health in remissive states of asthma for hundreds of years in Asia. However, little is known about the immunomodulatory mechanisms in vivo. Therefore, this study investigated the pathologic and immunologic responses to YGW in mice that had been repeatedly exposed to Dermatogoides-pteronyssinus (Der p). YGW reduced Der-p-induced airway hyperresponsiveness and total IgE in serum. It also inhibited eosinophil infiltration by downregulating the protein expression of IL-5 in serum and changed the Th2-bios in BALF by upregulating IL-12. Results of the collagen assay and histopathologic examination showed that YGW reduced airway remodeling in the lung. In addition, after YGW treatment there was a relative decrease in mRNA expression of TGF-beta1, IL-13, eotaxin, RANTES, and MCP-1 in lung in the YGW group. The results of EMSA and immunohistochemistry revealed that YGW inhibited NF-kappaB expression in epithelial lung cells. YGW exerts its regulative effects in chronic allergic asthmatic mice via its anti-inflammatory activity and by inhibiting the progression of airway remodeling. PMID- 22675382 TI - Biological Activities of Libidibia (Caesalpinia) ferrea var. parvifolia (Mart. ex Tul.) L. P. Queiroz Pod Preparations. AB - Libidibia ferrea has been used in folk medicine throughout Brazil, and this study evaluated the biological activities of crude extract (CE) as well as a partially purified fraction (F80) obtained from its pods. Results from the MTT assay revealed that only F80 inhibited NCI-H292 cell growth; however, neither CE nor F80 reduced HEp-2 cell growth or sarcoma 180 tumor weight with the in vivo assay. Acute oral toxicity of the extract and fraction was evaluated following the steps of Guideline 423, using female mice; LD(50) for both preparations was determined as 2,500 mg/kg body weight. CE and F80 promoted a reduction of the leukocyte number and nitrite level in inflammatory exudates when the anti-inflammatory assay (carrageenan-induced peritonitis) was performed. CE and F80 inhibited writhing regarding antinociceptive activity (acetic acid-induced writhing response in mice). In conclusion, CE and F80 have no significant cytotoxic or antitumor activities in cell lines showing low toxicity and no action against tumors in vivo. Both preparations revealed anti-inflammatory and antinociceptive activities, corroborating the pharmacological basis of L. ferrea for ethnomedical use. PMID- 22675383 TI - Effect of Cymbopogon citratus and Citral on Vascular Smooth Muscle of the Isolated Thoracic Rat Aorta. AB - Cymbopogon citratus has been shown to have antioxidant, antimicrobial, antispasmodic and chemo-protective properties. Citral, is the major constituent of C. citratus. This study investigated the effects of methanolic extracts of leaves (LE), stems (SE), and roots (RE) of C. citratus and citral on vascular smooth muscle and explored their possible mechanisms of action. The experiment was conducted using isolated tissue preparations, where citral, LE, SE, and RE were added separately into a tissue bath that contained aortic rings, which were pre-contracted with phenylephrine (PE). Citral, LE, and RE exhibited a dose dependent relaxant effect on the PE-induced contractions. Citral appeared to partially act via NO as its vasorelaxant effect was attenuated by L-NAME. However, the effect of LE may involve prostacyclin as indomethacin reversed the relaxant effect of LE on the PE-induced contraction. Furthermore, citral, LE, and RE abolished the restoration of PE-induced contraction caused by the addition of increasing doses of calcium in both endothelium intact and denuded rings. These findings suggest that the relaxation effect of citral, LE, and RE is endothelium independent and may be mainly by affecting the intracellular concentration of calcium. Citral may partially act through the NO pathway while a vasodilator prostaglandin may mediate the effect of LE. PMID- 22675384 TI - Early Blockade of TLRs MyD88-Dependent Pathway May Reduce Secondary Spinal Cord Injury in the Rats. AB - To determine the role of toll-like receptors (TLRs) myeloid differentiation factor 88 (MyD88) dependent pathway in the spinal cord secondary injury, compression injury was made at T8 segment of the spinal cord in adult male Sprague-Dawley rats. Shown by RT-PCR, TLR4 mRNA in the spinal cord was quickly elevated after compression injury. Intramedullary injection of MyD88 inhibitory peptide (MIP) resulted in significant improvement in locomotor function recovery at various time points after surgery. Meanwhile, injury area, p38 phosphorylation, and proinflammation cytokines in the injured spinal cord were significantly reduced in MIP-treated animals, compared with control peptide (CP) group. These data suggest that TLRs MyD88-dependent pathway may play an important role in the development of secondary spinal cord injury, and inhibition of this pathway at early time after primary injury could effectively protect cells from inflammation and apoptosis and therefore improve the functional recovery. PMID- 22675386 TI - Exploration of new electroacupuncture needle material. AB - Background. Electro Acupuncture (EA) uses the acupuncture needle as an electrode to apply low-frequency stimulation. For its safe operation, it is essential to prevent any corrosion of the acupuncture needle. Objective. The aim of this study is to find an available material and determine the possibility of producing a standard EA needle that is biocompatible. Methods. Biocompatibility was tested by an MTT assay and cytotoxicity testing. Corrosion was observed with a scanning electron microscope (SEM) after 0.5 mA, 60 min stimulation. The straightness was measured using a gap length of 100 mm, and tensile testing was performed by imposing a maximum tensile load. Results. Phosphor bronze, Ni coated SS304, were deemed inappropriate materials because of mild-to-moderate cytotoxicity and corrosion. Ti-6Al-4V and SS316 showed no cytotoxicity or corrosion. Ti-6Al-4V has a 70 times higher cost and 2.5 times lower conductivity than SS316. The results of both straightness and tensile testing confirmed that SS316 can be manufactured as a standard product. Conclusion. As a result, we confirmed that SS316 can be used a new EA electrode material. We hope that a further study of the maximum capacity of low-frequency stimulation using an SS316 for safe operation. PMID- 22675385 TI - Chronic Treatment with Squid Phosphatidylserine Activates Glucose Uptake and Ameliorates TMT-Induced Cognitive Deficit in Rats via Activation of Cholinergic Systems. AB - The present study examined the effects of squid phosphatidylserine (Squid-PS) on the learning and memory function and the neural activity in rats with TMT-induced memory deficits. The rats were administered saline or squid derived Squid-PS (Squid-PS 50 mg kg(-1), p.o.) daily for 21 days. The cognitive improving efficacy of Squid-PS on the amnesic rats, which was induced by TMT, was investigated by assessing the passive avoidance task and by performing choline acetyltransferase (ChAT) and acetylcholinesterase (AchE) immunohistochemistry. 18F Fluorodeoxyglucose and performed a positron emission tomography (PET) scan was also performed. In the passive avoidance test, the control group which were injected with TMT showed a markedly lower latency time than the non-treated normal group (P < 0.05). However, treatment of Squid-PS significantly recovered the impairment of memory compared to the control group (P < 0.05). Consistent with the behavioral data, Squid-PS significantly alleviated the loss of ChAT immunoreactive neurons in the hippocampal CA3 compared to that of the control group (P < 0.01). Also, Squid-PS significantly increased the AchE positive neurons in the hippocampal CA1 and CA3. In the PET analysis, Squid-PS treatment increased the glucose uptake more than twofold in the frontal lobe and the hippocampus (P < 0.05, resp.). These results suggest that Squid-PS may be useful for improving the cognitive function via regulation of cholinergic enzyme activity and neural activity. PMID- 22675387 TI - Metabolomics-based study of clinical and animal plasma samples in coronary heart disease with blood stasis syndrome. AB - The aim of this study is to explore a bridge connecting the mechanism basis and macro syndromes of coronary heart disease with experimental animal models. GC-MS technique was used to detect the metabolites of plasma samples in mini swine models with myocardial infarction (MI) and patients with unstable angina (UA). 30 metabolites were detected in the plasma samples of more than 50 percent of model group and control group in swine, while 37 metabolites were found in the plasma samples of UA patients and healthy control group. 21 metabolites in the plasma samples of swine model and 20 metabolites in patients with UA were found of significant value. Among which, 8 shared metabolites were found of low level expression in both swine model and UA patients. Independent Student's t-test, principal component analysis (PCA), and hierarchicalcluster analysis (HCA) were orderly applied to comprehend inner rules of variables in the data. The 8 shared metabolites could take place of the 21 or 20 metabolites in classification of swine model with MI and UA patients, which could be considered as a bridge connecting the mechanism basis and macrosyndromes of swine model with MI and UA patients. PMID- 22675388 TI - Study on TCM Syndrome Identification Modes of Coronary Heart Disease Based on Data Mining. AB - Coronary heart disease (CHD) is one of the most important types of heart disease because of its high incidence and high mortality. TCM has played an important role in the treatment of CHD. Syndrome differentiation based on information from traditional four diagnostic methods has met challenges and questions with the rapid development and wide application of system biology. In this paper, methods of complex network and CHAID decision tree were applied to identify the TCM core syndromes of patients with CHD, and to establish TCM syndrome identification modes of CHD based on biological parameters. At the same time, external validation modes were also constructed to confirm the identification modes. PMID- 22675389 TI - Antimicrobial Effects of a Lipophilic Fraction and Kaurenoic Acid Isolated from the Root Bark Extracts of Annona senegalensis. AB - Root bark preparation of Annona senegalensis Pers. (Annonaceae) is used in Nigerian ethnomedicine for treatment of infectious diseases. Extraction of the A. senegalensis powdered root bark with methanol-methylene chloride (1 : 1) mixture yielded the methanol-methylene extract (MME) which was fractionated to obtain the ethyl acetate fraction (EF). The EF on further fractionation gave two active subfractions, F1 and F2. The F1 yielded a lipophilic oily liquid while F2 on purification, precipitated white crystalline compound, AS2. F1 was analyzed using GC-MS, while AS2 was characterized by proton NMR and X-ray crystallography. Antibacterial and antifungal studies were performed using agar-well-diffusion method with 0.5 McFarland standard and MICs calculated. GC-MS gave 6 major constituents: kaur-16-en-19-oic acid; 1-dodecanol; 1-naphthalenemethanol; 6,6 dimethyl-bicyclo[3.1.1]hept-2-ene-2-ethanol; 3,3-dimethyl-2-(3-methylbuta-1,3 dienyl)cyclohexane-1-methanol; 3-hydroxyandrostan-17-carboxylic acid. AS2 was found to be kaur-16-en-19-oic acid. The MICs of EF, F1, and AS2 against B. subtilis were 180, 60, and 30 MUg/mL, respectively. AS2 exhibited activity against S. aureus with an MIC of 150 MUg/mL, while F1 was active against P. aeruginosa with an MIC of 40 MUg/mL. However, the extracts and AS2 exhibited no effects against Candida albicans and Aspergillus niger. Therefore, kaurenoic acid and the lipophilic fraction from A. senegalensis root bark exhibited potent antibacterial activity. PMID- 22675390 TI - Evaluation of the Acetone and Aqueous Extracts of Mature Stem Bark of Sclerocarya birrea for Antioxidant and Antimicrobial Properties. AB - We assayed the antimicrobial activity of acetone and aqueous extracts of the stem bark of Sclerocarya birrea on some selected bacteria and fungi species including; Streptococcus pyogenes, Plesiomonas shigelloides, Aeromonas hydrophila, Salmonella typhimurium, Cryptococcus neoformans, Candida glabrata, Trichosporon mucoides, and Candida krusei using both agar well diffusion and minimum inhibitory concentration (MIC) assays. Based on the levels of activity, the acetone extract was examined for total polyphenolic content, radical scavenging and antioxidant activities. Total phenols of the extract were determined spectrophotometrically. The antioxidant activity was determined by the DPPH, ABTS and reducing power. All the bacteria and fungi species were susceptible to the plant extracts. The acetone extract was the most active for the bacterial species with MIC (0.156-0.625 mg/mL) while the aqueous extract was the most active for the fungi species with MIC (0.3125-1.25 mg/mL). The polyphenolic compounds were found as 27.2 mg/g tannic acid equivalent, 25.2 mg/g quercetin equivalent, 9.1 mg/g quercetin equivalent for phenols, flavonoid and flavonols respectively. The acetone extract exhibited a remarkable ability to scavenge radicals, strong reducing ability and a potential source of natural antioxidants. Both the acetone and aqueous extracts of S. birrea may provide a target for drug discovery. PMID- 22675391 TI - Haemodynamic changes in the superior mesenteric artery induced by acupuncture stimulation on the lower limbs. AB - Acupuncture is commonly performed on acupoints. A comparison of quantitative physiological alterations induced by stimulation on different acupoints has never been performed in the superior mesenteric artery (SMA) in humans. Therefore, we investigated changes in blood flow volume (BFV) in the SMA as an indicator of physiological effects induced by stimulation on 3 points. Thirty healthy participants aged 29 +/- 10 years (mean +/- SD) were enrolled. All participants underwent stimulations on 3 points located in the lower legs: ST36, LR3, and a non-acupoint. Control pertains to a condition with no-stimulation. Stimulation was performed bilaterally with manual rotation of the needles. BFV was measured by ultrasonography before insertion and 10, 20, 30, and 60 minutes after stimulation. Following acupuncture on ST36, BFV increased significantly 20 and 30 minutes after stimulation, compared to BFV before insertion (P < 0.05). Following stimulation on LR3 and the non-acupoint, no significant differences in BFV could be found. Relative to the no-stimulation group, stimulation on LR3, and the non acupoint, stimulation on ST36 elicited a significant increase in BFV (P < 0.05). The results suggest that stimulation on the different points causes distinct physiological effects in BFV in the SMA. PMID- 22675392 TI - Impact of transcendental meditation on left ventricular mass in african american adolescents. AB - Background. An early sign of ventricular remodeling is increased left ventricular mass (LVM) which over time may lead to left ventricular hypertrophy, the strongest predictor of cardiovascular morbidity and mortality, other than advancing age. Methods. 62 (30 TM; 32 CTL) African American adolescents (age 16.2 +/- 1.3 years) with high normal systolic BP were randomly assigned to either 4 month Transcendental Meditation (TM) or health education control groups. The echocardiographic-derived measure of LVM index (LVMI = LVM/ht(2.7)) was measured before and after the 4-month TM study and at 4-month followup. 2D-guided M-mode echocardiography using a Hewlett Packard 5500 echosonograph was used to determine LVMI. Results. The TM group exhibited a greater decrease in LVMI at 4-month followup compared to the CTL group (-2.6 versus +0.3 gm/ht(2.7), P < 0.04). The TM group exhibited a lesser increase in BMI at 4-month follow-up compared to the CTL group (0.2 +/- 1.6 versus 1.1 +/- 1.4, P < 0.03). Conclusion. These findings indicate that among a group of prehypertensive African American adolescents, 4 months of TM compared to heath education resulted in a significant decrease in LVMI, and these changes were maintained at 4-month follow-up. PMID- 22675393 TI - Preparation of blood-deficient model and research of angelica polysaccharide on enriching blood in chickens. AB - In this study cyclophosphamide was used to prepare the blood-deficient model. The red blood cell count and hemoglobin content were measured. The experimental chickens presented the symptoms of blood-deficient syndrome, dullness, shrinkinginto oneself, broken winded, loose feather, waxy eyelid, and pale tongue. At the same time, red blood cell count and hemoglobin content decreased significantly. Angelica polysaccharide as the effective component of Angelica Sinensis could significantly increase the red blood cell count and the hemoglobin content of blood-deficient chickens. The results indicated that cyclophosphamide could significantly reduce the red blood count and hemoglobin content, and make the ideal blood-deficient model successfully. Angelica polysaccharide had the function of enriching blood in different ways. On the one hand Angelica polysaccharide enriched he blood directly, increased the number of RBC and hemoglobin; on the other hand it regulated the hematopoietic factors, enriched the blood indirectly. PMID- 22675394 TI - Selected Extracts of Chinese Herbal Medicines: Their Effect on NF-kappaB, PPARalpha and PPARgamma and the Respective Bioactive Compounds. AB - Chinese herbal medicinal (CHM) extracts from fourteen plants were investigated in cell-based in vitro assays for their effect on nuclear factor kappaB (NF-kappaB), a key regulator of inflammation, as well as on peroxisome proliferator-activated receptors (PPARs) being key regulators of genes involved in lipid and glucose metabolism. 43% of the investigated CHMs showed NF-kappaB inhibitory and 50% PPARalpha and PPARgamma activating effects. Apolar extracts from cortex and flos of Albizia julibrissin Durazz. and processed rhizomes of Arisaema sp. and Pinellia ternata (Thunb.) Breit. that effectively inhibited TNF-alpha-induced NF kappaB activation and dose-dependently activated PPARalpha and PPARgamma were further investigated. Bioassay-guided fractionation and analysis by GC-MS led to the identification of fatty acids as PPAR agonists, including linoleic and palmitic acid. PMID- 22675396 TI - Testosterone for low libido in postmenopausal women? AB - Use of testosterone in older woman with hypoactive sexual-desire disorder (HSDD) is controversial. One concern about existing testosterone therapies for HSDD is the common recommendation to concomitantly administer estradiol because of the known risks of such therapy in postmenopausal women. This large, year-long, double-blind, placebo-controlled trial of testosterone therapy in postmenopausal women examined the hypothesis that testosterone alone would be efficacious in improving HSDD. The results of this trial confirm the improvement in sexual function for postmenopausal women seen in earlier studies using testosterone in combination with estradiol, implying that estradiol administration may not be essential for the beneficial effects of testosterone. However, this study raised some concerns regarding testosterone therapy on the risk of breast and endometrial cancer, highlighting the need for further long-term trials to better assess the long-term safety of this approach for the treatment of HSDD in women. PMID- 22675395 TI - Virtual microscopy in cytotechnology education: Application of knowledge from virtual to glass. AB - BACKGROUND: Virtual microscopy (VM) is a technology in which the glass slides are converted into digital images. The main objective of this study is to determine if cellular morphology, learned through virtual microscopy, can be applied to glass slide screening. MATERIALS AND METHODS: A total of 142 glass slides (61 teaching and 81 practice) of breast, thyroid, and lymph node fine needle aspiration body sites were scanned with a single focal plane (at 40X) using iScanCoreo Au (Ventana, Tuscan, AZ, USA, formerly known as BioImagene, California, USA). Six students including one distant student used these digital images to learn cellular morphology and conduct daily screening. Subsequently, all the students were tested on 10 glass slides using light microscopy (LM). At the end of the study, the students were asked to respond to an online survey on their virtual microscopy experience. The glass slide screening test scores of the participating students who were taught through VM and tested on glass slides (VMLM group) were compared with the last three classes of students who were taught through LM and tested on glass slides (LMLM group). RESULTS: A non parametric statistical analysis indicated no difference (P = 0.20) in the glass screening test scores between VMLM (median = 93.5) and LMLM groups (median = 87). The survey indicated that the annotated teaching slides and access to the VM, off campus, were well appreciated by the students. CONCLUSIONS: Although the students preferred LM, they were able to apply the cytological criteria learned through VM to glass slide screening. Overall, VM was considered a great teaching tool. PMID- 22675397 TI - A short version of the revised 'experience of close relationships questionnaire': investigating non-clinical and clinical samples. AB - AIM: This study seeks to investigate the psychometric properties of the short version of the revised 'Experience of Close Relationships' questionnaire, comparing non-clinical and clinical samples. METHODS: In total 702 subjects participated in this study, of whom 531 were non-clinical participants and 171 were psychiatric patients. They completed the short version of the revised 'Experience of Close Relationships' questionnaire (ECR-R-18), the Perceived Stress Scale-10(PSS-10), the Rosenberg Self-Esteem Scale (RSES) and the UCLA Loneliness scale. A retest of the ECR-R-18 was then performed at four-week intervals. Then, confirmatory factor analyses were performed to test the validity of the new scale. RESULTS: The ECR-R-18 showed a fair to good internal consistency (alpha 0.77 to 0.87) for both samples, and the test-retest reliability was found to be satisfactory (ICC = 0.75). The anxiety sub-scale demonstrated concurrent validity with PSS-10 and RSES, while the avoidance sub scale showed concurrent validity with the UCLA Loneliness Scale. Confirmatory factor analysis using method factors yielded two factors with an acceptable model fit for both groups. An invariance test revealed that the ECR-R-18 when used on the clinical group differed from when used with the non-clinical group. CONCLUSIONS: The ECR-R-18 questionnaire revealed an overall better level of fit than the original 36 item questionnaire, indicating its suitability for use with a broader group of samples, including clinical samples. The reliability of the ECR-R- 18 might be increased if a modified scoring system is used and if our suggestions with regard to future studies are followed up. PMID- 22675398 TI - Trichophagia and trichobezoar: case report. AB - OBJECTIVE: Trichobezoar consists of a compact mass of hair occupying the gastric cavity to a various extent. When the trichobezoar extends past the duodenum it is better referred to as Rapunzel Syndrome. Although trichobezoars are well described in terms of surgical diagnostic and procedure, there are only but very scarce reports on psychiatric literature, usually associated with trichotillomania. The authors present a clinical case of trichobezoar and discuss the most relevant aspects concerning this entity. METHODS: Presentation of psychiatric and surgical data concerning the case report. Previously reported cases are also mentioned. RESULTS: Report of a 27-year-old female patient with a trichobezoar submitted to surgical removal, with a prior intervention 4 years before also due to trichobezoar, and with unknown psychiatric antecedents or follow-up. CONCLUSIONS: A trichobezoar represents a serious surgical condition. It is important to consider such diagnosis in face of suggestive symptoms, even if signs of trichotillomania are not present. The discrepancies between the prevalence of trichotillomania and trichobezoars due to trichophagia may be due to issues related to self-selection of patients and symptom severity. Such issues may also be important in the study of impulsive-compulsive spectrum models and to their relevance to impulse control disorders. PMID- 22675399 TI - Molecular dynamics simulation of HIV fusion inhibitor T-1249: insights on peptide lipid interaction. AB - T-1249 is a peptide that inhibits the fusion of HIV envelope with the target cell membrane. Recent results indicate that T-1249, as in the case of related inhibitor peptide T-20 (enfuvirtide), interacts with membranes, more extensively in the bilayer liquid disordered phase than in the liquid ordered state, which could be linked to its effectiveness. Extensive molecular dynamics simulations (100 ns) were carried out to investigate the interaction between T-1249 and bilayers of 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) and POPC/cholesterol (1 : 1). It was observed that T-1249 interacts to different extents with both membrane systems and that peptide interaction with the bilayer surface has a local effect on membrane structure. Formation of hydrogen bonding between certain peptide residues and several acceptor and donor groups in the bilayer molecules was observed. T-1249 showed higher extent of interaction with bilayers when compared to T-20. This is most notable in POPC/Chol membranes, owing to more peptide residues acting as H bond donors and acceptors between the peptide and the bilayer lipids, including H-bonds formed with cholesterol. This behavior is at variance with that of T-20, which forms no H bonds with cholesterol. This higher ability to interact with membranes is probably correlated with its higher inhibitory efficiency. PMID- 22675400 TI - Causal information approach to partial conditioning in multivariate data sets. AB - When evaluating causal influence from one time series to another in a multivariate data set it is necessary to take into account the conditioning effect of the other variables. In the presence of many variables and possibly of a reduced number of samples, full conditioning can lead to computational and numerical problems. In this paper, we address the problem of partial conditioning to a limited subset of variables, in the framework of information theory. The proposed approach is tested on simulated data sets and on an example of intracranial EEG recording from an epileptic subject. We show that, in many instances, conditioning on a small number of variables, chosen as the most informative ones for the driver node, leads to results very close to those obtained with a fully multivariate analysis and even better in the presence of a small number of samples. This is particularly relevant when the pattern of causalities is sparse. PMID- 22675401 TI - Quantification of effective connectivity in the brain using a measure of directed information. AB - Effective connectivity refers to the influence one neural system exerts on another and corresponds to the parameter of a model that tries to explain the observed dependencies. In this sense, effective connectivity corresponds to the intuitive notion of coupling or directed causal influence. Traditional measures to quantify the effective connectivity include model-based methods, such as dynamic causal modeling (DCM), Granger causality (GC), and information-theoretic methods. Directed information (DI) has been a recently proposed information theoretic measure that captures the causality between two time series. Compared to traditional causality detection methods based on linear models, directed information is a model-free measure and can detect both linear and nonlinear causality relationships. However, the effectiveness of using DI for capturing the causality in different models and neurophysiological data has not been thoroughly illustrated to date. In addition, the advantage of DI compared to model-based measures, especially those used to implement Granger causality, has not been fully investigated. In this paper, we address these issues by evaluating the performance of directed information on both simulated data sets and electroencephalogram (EEG) data to illustrate its effectiveness for quantifying the effective connectivity in the brain. PMID- 22675403 TI - Arts practices in unreasonable doubt? Reflections on understandings of arts practices in healthcare contexts. AB - This article suggests that the discourse on arts and health encompass contemporary arts practices as an active and engaged analytical activity. Distinctions between arts therapy and arts practice are made to suggest that clinical evidence-based evaluation, while appropriate for arts therapy, is not appropriate for arts practice and in effect cast them in unreasonable doubt. Themes in current discourse on "arts" and "health" are broadly sketched to provide a context for discussion of arts practices. Approaches to knowledge validation in relation to each domain are discussed. These discourses are applied to the Irish healthcare context, offering a reading of three different art projects; it suggests a multiplicity of analyses beyond causal positive health gains. It is suggested that the social turn in medicine and the social turn in arts practices share some similar pre-occupations that warrant further attention. PMID- 22675402 TI - Coarse-grained simulation of myosin-V movement. AB - We describe the development of a hierarchic modelling method applied to simulating the processive movement of the myosin-V molecular motor protein along an actin filament track. In the hierarchic model, three different levels of protein structure resolution are represented: secondary structure, domain, and protein, with the level of detail changing according to the degree of interaction among the molecules. The integrity of the system is maintained using a tree of spatially organised bounding volumes and distance constraints. Although applied to an actin-myosin system, the hierarchic framework is general enough so that it may easily be adapted to a number of other large biomolecular systems containing in the order of 100 proteins. We compared the simulation results with biophysical data, and despite the lack of atomic detail in our model, we find good agreement and can even suggest some refinements to the current model of myosin-V motion. PMID- 22675404 TI - How I do it: Simple and effortless approach to identify thoracodorsal nerve on axillary clearance procedure. AB - Breast cancer surgery frequently involves an axillary clearance procedure for nodal metastases. Injury to the thoracodorsal nerve is one of the complications related to the axillary dissection. The thoracodorsal nerve innervates the latissimus dorsi muscle which facilitates in certain movements of the arm. Moreover, it can be used as a nerve graft in long thoracic nerve injury whether in trauma or surgery. Understanding the anatomy structures and good surgical technique in the axillary clearance procedure can identify and prevent such an injury to the thoracodorsal nerve. Here, we demonstrate a simple and effortless technique for identification of the thoracodorsal nerve during axillary surgery. PMID- 22675405 TI - Cardiogenic shock due to myocardial infarction: diagnosis, monitoring and treatment: a German-Austrian S3 Guideline. AB - INTRODUCTION: Infarction-related cardiogenic shock (ICS) is usually due to left ventricular pump failure. With a mortality of 30% to 80%, ICS is the most common cause of death from acute myocardial infarction. The S3 guideline presented here characterizes the current evidence-based treatment of ICS: early revascularization, treatment of shock, and intensive care treatment of multi organ dysfunction syndrome (MODS) if it arises. The success or failure of treatment for MODS determines the outcome in ICS. METHODS: Experts from eight German and Austrian specialty societies analyzed approximately 3600 publications that had been retrieved by a systematic literature search. Three interdisciplinary consensus conferences were held, resulting in the issuing of 111 recommendations and algorithms for this S3 guideline. RESULTS: Early revascularization of the occluded vessel, usually with a percutaneous coronary intervention (PCI), is of paramount importance. The medical treatment of shock consists of dobutamine as the inotropic agent and norepinephrine as the vasopressor of choice and is guided by a combination of pressure and flow values, or by the cardiac power index. Levosimendan can be given in addition to treat catecholamine-resistant shock. For patients with ICS who are treated with PCI, the current S3 guideline differs from the European and American myocardial infarction guidelines with respect to the recommendation for intra-aortic balloon pulsation (IABP): Whereas the former guidelines give a class I recommendation for IABP, this S3 guideline states only that IABP "can" be used in this situation, in view of the poor state of the evidence. Only for patients being treated with systemic fibrinolysis is IABP weakly recommended (IABP "should" be used in such cases). With regard to the optimal intensive-care interventions for the prevention and treatment of MODS, recommendations are given concerning ventilation, nutrition, erythrocyte-concentrate transfusion, prevention of thrombosis and stress ulcers, follow-up care, and rehabilitation. DISCUSSION: The goal of this S3 guideline is to bring together the types of treatment for ICS that lie in the disciplines of cardiology and intensive-care medicine, as patients with ICS die not only of pump failure, but also (and even more frequently) of MODS. This is the first guideline that adequately emphasizes the significance of MODS as a determinant of the outcome of ICS. PMID- 22675406 TI - Current standards in the treatment of chronic hepatitis C. AB - BACKGROUND: In Germany, 400 000 to 500 000 people are chronically infected with the hepatitis C virus (HCV), 70% to 80% of them with HCV genotype 1. Combined treatment with peginterferon-alfa and ribavirin leads to a sustained virologic response (SVR) in 40% to 50% of patients with genotype 1 and 70% to 80% of patients with genotypes 2 and 3. The HCV protease inhibitors boceprevir and telaprevir were approved for clinical use in Germany in 2011. METHODS: Selective literature review. RESULTS: Treatment with peginterferon and ribavirin is recommended for a variable length of time depending on the HCV genotype (24 to 72 weeks for genotype 1, 16 to 48 weeks for genotypes 2 and 3), the baseline HCV-RNA concentration (greater or less than 600 000 to 800 000 IU/mL), and the decline in HCV-RNA concentration after 4 and 12 weeks of treatment. Either boceprevir or telaprevir is given in addition to peginterferon and ribavirin. In the approval studies, these triple combinations were shown to yield higher SVR rates than dual treatment for genotype 1 (66% to 75% versus 37% to 44%). If there is a favorable early decline in HCV-RNA, the treatment can be shortened to 24 to 28 weeks in 44% to 65% of patients with genotype 1. The SVR rates in genotype 1 patients who failed previous dual therapy were 69% to 88% for prior relapsers, 52% to 59% for partial responders, and 33% for null responders. Triple combination therapy is associated with new adverse events. CONCLUSION: Individualized treatment durations are recommended for the treatment of chronic hepatitis C with peginterferon and ribavirin. Triple therapy in combination with either boceprevir or telaprevir leads to a higher rate of SVR both in previously untreated genotype 1 patients and in those who have failed prior antiviral treatment.? PMID- 22675407 TI - Correspondence (letter to the editor): Appeal for vitamin D therapy. PMID- 22675409 TI - Biomechanical in vitro - stability testing on human specimens of a locking plate system against conventional screw fixation of a proximal first metatarsal lateral displacement osteotomy. AB - INTRODUCTION: The aim of this study was to examine resistance to angulation and displacement of the internal fixation of a proximal first metatarsal lateral displacement osteotomy, using a locking plate system compared with a conventional crossed screw fixation. MATERIALS AND METHODOLOGY: Seven anatomical human specimens were tested. Each specimen was tested with a locking screw plate as well as a crossed cancellous srew fixation. The statistical analysis was performed by the Friedman test. The level of significance was p = 0.05. RESULTS: We found larger stability about all three axes of movement analyzed for the PLATE than the crossed screws osteosynthesis (CSO). The Friedman test showed statistical significance at a level of p = 0.05 for all groups and both translational and rotational movements. CONCLUSION: The results of our study confirm that the fixation of the lateral proximal first metatarsal displacement osteotomy with a locking plate fixation is a technically simple procedure of superior stability. PMID- 22675410 TI - Wrist MRI Arthrogram v Wrist Arthroscopy: What are we Finding? AB - The aim of the study was to compare the radiological findings of wrist arthrogram with wrist arthroscopy. This allowed us to establish the accuracy (sensitivity, specificity) of MRI arthrogram as a diagnostic tool. Thirty patients (20 female and 10 male) have undergone both wrist MRI arthrogram and wrist arthroscopy over the last 3 years at a District General Hospital. The mean age at arthrogram was 42.4 years with an average 6.7 month interval between the two procedures.The MRI arthrogram was reported by a consultant radiologist with an interest in musculoskeletal imaging and the arthroscopies performed by two upper limb surgeons. Patients who underwent both procedures were identified. The arthrogram reports and operation notes were examined for correlation. Three main areas of pathology were consistently examined: TFCC (triangular fibrocartilage complex), scapholunate and lunotriquetral ligament tears. The sensitivity and specificity of arthrogram was calculated for each. Other areas of pathology were also noted.In the case of TFCC tears MRI arthrogram had 90% sensitivity and 75% specificity. The lunotriquetral ligament examination with this technique was 100% sensitivity and specificity. However for scapholunate ligament tears it only had 91% sensitivity and 88% specificity.Wrist arthrogram and arthroscopy are both invasive techniques. In cost terms the arthrogram remains cheaper but is superseded by arthroscopy as it is both diagnostic and therapeutic. PMID- 22675411 TI - Clinical and non-clinical aspects of distal radioulnar joint instability. AB - Untreated distal radioulnar joint (DRUJ) injuries can give rise to long lasting complaints. Although common, diagnosis and treatment of DRUJ injuries remains a challenge. The articulating anatomy of the distal radius and ulna, among others, enables an extensive range of forearm pronosupination movements. Stabilization of this joint is provided by both intrinsic and extrinsic stabilizers and the joint capsule. These structures transmit the load and prevent the DRUJ from luxation during movement. Several clinical tests have been suggested to determine static or dynamic DRUJ stability, but their predictive value is unclear. Radiologic evaluation of DRUJ instability begins with conventional radiographs in anterioposterior and true lateral view. If not conclusive, CT-scan seems to be the best additional modality to evaluate the osseous structures. MRI has proven to be more sensitive and specific for TFCC tears, potentially causing DRUJ instability. DRUJ instability may remain asymptomatic. Symptomatic DRUJ injuries treatment can be conservative or operative. Operative treatment should consist of restoration of osseous and ligamenteous anatomy. If not successful, salvage procedures can be performed to regain stability. PMID- 22675412 TI - Successful closed reduction of a dislocated constrained total hip arthroplasty: a case report and literature review. AB - Many surgeons use acetabular components with constrained polyethylene liners to improve stability after total hip arthroplasty in patients with a history of hip dislocation. Surgical treatment is generally thought to be the only available option for the dislocated constrained liner. The success rate and clinical results of closed reduction for such patients is unclear. This report presents a case of a successful closed reduction of a dislocated constrained liner. Few papers have so far addressed closed reduction of a dislocated constrained liner. Furthermore, previous studies reported a variety of components. Publication of additional successful and unsuccessful case reports is therefore needed to help establish the optimal treatment protocol for a dislocated constrained liner. PMID- 22675413 TI - Importance of preoperative imaging in acetabular revision surgery - a case report. AB - Acetabular defects, particularly as a result of protrusion of acetabular components into the hemipelvis, may cause serious complications during revision procedures as a result of iatrogenic injury to surrounding anatomical structures. In these challenging cases, we advocate the utilisation of preoperative three dimensional imaging. MRI and CT- imaging offer superior understanding of the three-dimensional quality of bony defects and the relationship of implants to important anatomical structures. Appropriate preoperative planning may also prevent major complications during the removal of the pre-existing hardware, prior to re-implantation of implants. Potential complications include injury of nerves, blood vessels and other intrapelvic structures.In our case, a major bony defect of the acetabulum was a result of the protrusion of an implanted reinforcement ring. A preoperative, contrast-enhanced CT scan showed that the urethra was in close proximity to the hook of the reinforcement ring.The preoperative imaging aided in identifying and understanding the potential complications that could occur intraoperatively. Additionally, it delineated the intact anatomic structures prior to surgery, which could have medico-legal implications.The importance of preoperative imaging and the existing literature is discussed within this case description. PMID- 22675414 TI - Editorial to the special issue Implicit Serial Learning. PMID- 22675421 TI - A quasi-exclusive European ancestry in the Senepol tropical cattle breed highlights the importance of the slick locus in tropical adaptation. AB - BACKGROUND: The Senepol cattle breed (SEN) was created in the early XX(th) century from a presumed cross between a European (EUT) breed (Red Poll) and a West African taurine (AFT) breed (N'Dama). Well adapted to tropical conditions, it is also believed trypanotolerant according to its putative AFT ancestry. However, such origins needed to be verified to define relevant husbandry practices and the genetic background underlying such adaptation needed to be characterized. METHODOLOGY/PRINCIPAL FINDINGS: We genotyped 153 SEN individuals on 47,365 SNPs and combined the resulting data with those available on 18 other populations representative of EUT, AFT and Zebu (ZEB) cattle. We found on average 89% EUT, 10.4% ZEB and 0.6% AFT ancestries in the SEN genome. We further looked for footprints of recent selection using standard tests based on the extent of haplotype homozygosity. We underlined i) three footprints on chromosome (BTA) 01, two of which are within or close to the polled locus underlying the absence of horns and ii) one footprint on BTA20 within the slick hair coat locus, involved in thermotolerance. Annotation of these regions allowed us to propose three candidate genes to explain the observed signals (TIAM1, GRIK1 and RAI14). CONCLUSIONS/SIGNIFICANCE: Our results do not support the accepted concept about the AFT origin of SEN breed. Initial AFT ancestry (if any) might have been counter-selected in early generations due to breeding objectives oriented in particular toward meat production and hornless phenotype. Therefore, SEN animals are likely susceptible to African trypanosomes which questions the importation of SEN within the West African tsetse belt, as promoted by some breeding societies. Besides, our results revealed that SEN breed is predominantly a EUT breed well adapted to tropical conditions and confirmed the importance in thermotolerance of the slick locus. PMID- 22675422 TI - Melanoma chemotherapy leads to the selection of ABCB5-expressing cells. AB - Metastatic melanoma is the most aggressive skin cancer. Recently, phenotypically distinct subpopulations of tumor cells were identified. Among them, ABCB5 expressing cells were proposed to display an enhanced tumorigenicity with stem cell-like properties. In addition, ABCB5(+) cells are thought to participate to chemoresistance through a potential efflux function of ABCB5. Nevertheless, the fate of these cells upon drugs that are used in melanoma chemotherapy remains to be clarified. Here we explored the effect of anti-melanoma treatments on the ABCB5-expressing cells. Using a melanoma xenograft model (WM266-4), we observed in vivo that ABCB5-expressing cells are enriched after a temozolomide treatment that induces a significant tumor regression. These results were further confirmed in a preliminary study conducted on clinical samples from patients that received dacarbazine. In vitro, we showed that ABCB5-expressing cells selectively survive when exposed to dacarbazine, the reference treatment of metastatic melanoma, but also to vemurafenib, a new inhibitor of the mutated kinase V600E BRAF and other various chemotherapeutic drugs. Our results show that anti-melanoma chemotherapy might participate to the chemoresistance acquisition by selecting tumor cell subpopulations expressing ABCB5. This is of particular importance in understanding the relapses observed after anti-melanoma treatments and reinforces the interest of ABCB5 and ABCB5-expressing cells as potential therapeutic targets in melanoma. PMID- 22675423 TI - Double digest RADseq: an inexpensive method for de novo SNP discovery and genotyping in model and non-model species. AB - The ability to efficiently and accurately determine genotypes is a keystone technology in modern genetics, crucial to studies ranging from clinical diagnostics, to genotype-phenotype association, to reconstruction of ancestry and the detection of selection. To date, high capacity, low cost genotyping has been largely achieved via "SNP chip" microarray-based platforms which require substantial prior knowledge of both genome sequence and variability, and once designed are suitable only for those targeted variable nucleotide sites. This method introduces substantial ascertainment bias and inherently precludes detection of rare or population-specific variants, a major source of information for both population history and genotype-phenotype association. Recent developments in reduced-representation genome sequencing experiments on massively parallel sequencers (commonly referred to as RAD-tag or RADseq) have brought direct sequencing to the problem of population genotyping, but increased cost and procedural and analytical complexity have limited their widespread adoption. Here, we describe a complete laboratory protocol, including a custom combinatorial indexing method, and accompanying software tools to facilitate genotyping across large numbers (hundreds or more) of individuals for a range of markers (hundreds to hundreds of thousands). Our method requires no prior genomic knowledge and achieves per-site and per-individual costs below that of current SNP chip technology, while requiring similar hands-on time investment, comparable amounts of input DNA, and downstream analysis times on the order of hours. Finally, we provide empirical results from the application of this method to both genotyping in a laboratory cross and in wild populations. Because of its flexibility, this modified RADseq approach promises to be applicable to a diversity of biological questions in a wide range of organisms. PMID- 22675424 TI - ADH1C Ile350Val polymorphism and cancer risk: evidence from 35 case-control studies. AB - BACKGROUND: Alcohol dehydrogenase 1C (ADH1C) is the key enzyme catalyze oxidation of alcohol to acetaldehyde, which plays vital roles in the etiology of various cancer. To date, studies investigated the association between a functional polymorphism in ADH1C, Ile350Val (rs698), and risk of cancer have shown inclusive results. METHODS: A meta-analysis based on 35 case-control studies was performed to address this issue. Odds ratios (OR) with 95% confidence intervals (CIs) were used to assess the association. The statistical heterogeneity across studies was examined with chi2-based Q-test. RESULTS: Overall, no significant associations between ADH1C Ile350Val polymorphism and cancer risk were observed in any genetic models (P>0.05). In the stratified analyses, there was a significantly increased cancer risk among African (Val/Val vs. Ile/Ile OR = 2.19, 95% CI = 1.29-3.73, P(heterogeneity) = 0.989; Ile/Val + Val/Val vs. Ile/Ile: OR = 1.79, 95%CI = 1.18-2.71, P(heterogeneity) = 0.761; Val/Val vs. Ile/Val + Ile/Ile: OR = 1.92, 95% CI = 1.16-3.17, P(heterogeneity) = 0.981) and Asian (Ile/Val vs. Ile/Ile: OR = 1.58, 95% CI = 1.32-1.90, P(heterogeneity) = 0.375; Val/Val vs. Ile/Ile: OR = 3.84, 95% CI = 1.74-8.49, P(heterogeneity) = 0.160; Ile/Val + Val/Val vs. Ile/Ile: OR = 1.65, 95% CI = 1.38-1.96, P(heterogeneity) = 0.330; Val/Val vs. Ile/Val + Ile/Ile: OR = 3.54, 95% CI = 1.62-7.75, P(heterogeneity) = 0.154) studies. CONCLUSIONS: The results indicate that ADH1C Ile350Val polymorphism may contribute to cancer risk among Africans and Asians. Additional comprehensive system analyses are required to validate this association combined with other related polymorphisms. PMID- 22675425 TI - Population structure and gene flow of the yellow anaconda (Eunectes notaeus) in northern Argentina. AB - Yellow anacondas (Eunectes notaeus) are large, semiaquatic boid snakes found in wetland systems in South America. These snakes are commercially harvested under a sustainable management plan in Argentina, so information regarding population structuring can be helpful for determination of management units. We evaluated genetic structure and migration using partial sequences from the mitochondrial control region and mitochondrial genes cyt-b and ND4 for 183 samples collected within northern Argentina. A group of landscape features and environmental variables including several treatments of temperature and precipitation were explored as potential drivers of observed genetic patterns. We found significant population structure between most putative population comparisons and bidirectional but asymmetric migration in several cases. The configuration of rivers and wetlands was found to be significantly associated with yellow anaconda population structure (IBD), and important for gene flow, although genetic distances were not significantly correlated with the environmental variables used here. More in-depth analyses of environmental data may be needed to fully understand the importance of environmental conditions on population structure and migration. These analyses indicate that our putative populations are demographically distinct and should be treated as such in Argentina's management plan for the harvesting of yellow anacondas. PMID- 22675426 TI - Conserved expression of the glutamate NMDA receptor 1 subunit splice variants during the development of the Siberian hamster suprachiasmatic nucleus. AB - Glutamate neurotransmission and the N-methyl-D-aspartate receptor (NMDAR) are central to photic signaling to the master circadian pacemaker located in the hypothalamic suprachiasmatic nucleus (SCN). NMDARs also play important roles in brain development including visual input circuits. The functional NMDAR is comprised of multiple subunits, but each requiring the NR1 subunit for normal activity. The NR1 can be alternatively spliced to produce isoforms that confer different functional properties on the NMDAR. The SCN undergoes extensive developmental changes during postnatal life, including synaptogenesis and acquisition of photic signaling. These changes are especially important in the highly photoperiodic Siberian hamster, in which development of sensitivity to photic cues within the SCN could impact early physiological programming. In this study we examined the expression of NR1 isoforms in the hamster at different developmental ages. Gene expression in the forebrain was quantified by in situ hybridization using oligonucleotide probes specific to alternatively spliced regions of the NR1 heteronuclear mRNA, including examination of anterior hypothalamus, piriform cortex, caudate-putamen, thalamus and hippocampus. Gene expression analysis within the SCN revealed the absence of the N1 cassette, the presence of the C2 cassette alone and the combined absence of C1 and C2 cassettes, indicating that the dominant splice variants are NR1-2a and NR1-4a. Whilst we observe changes at different developmental ages in levels of NR1 isoform probe hybridization in various forebrain structures, we find no significant changes within the SCN. This suggests that a switch in NR1 isoform does not underlie or is not produced by developmental changes within the hamster SCN. Consistency of the NR1 isoforms would ensure that the response of the SCN cells to photic signals remains stable throughout life, an important aspect of the function of the SCN as a responder to environmental changes in quality/quantity of light over the circadian day and annual cycle. PMID- 22675427 TI - Epidemiological and virological characteristics of influenza in the Western Pacific Region of the World Health Organization, 2006-2010. AB - BACKGROUND: Influenza causes yearly seasonal epidemics and periodic pandemics. Global systems have been established to monitor the evolution and impact of influenza viruses, yet regional analysis of surveillance findings has been limited. This study describes epidemiological and virological characteristics of influenza during 2006-2010 in the World Health Organization's Western Pacific Region. METHODOLOGY/PRINCIPAL FINDINGS: Influenza-like illness (ILI) and influenza virus data were obtained from the 14 countries with National Influenza Centres. Data were obtained directly from countries and from FluNet, the web based tool of the Global Influenza Surveillance and Response System. National influenza surveillance and participation in the global system increased over the five years. Peaks in ILI reporting appeared to be coincident with the proportion of influenza positive specimens. Temporal patterns of ILI activity and the proportion of influenza positive specimens were clearly observed in temperate countries: Mongolia, Japan and the Republic of Korea in the northern hemisphere, and Australia, New Zealand, Fiji and New Caledonia (France) in the southern hemisphere. Two annual peaks in activity were observed in China from 2006 through the first quarter of 2009. A temporal pattern was less evident in tropical countries, where influenza activity was observed year-round. Influenza A viruses accounted for the majority of viruses reported between 2006 and 2009, but an equal proportion of influenza A and influenza B viruses was detected in 2010. CONCLUSIONS/SIGNIFICANCE: Despite differences in surveillance methods and intensity, commonalities in ILI and influenza virus circulation patterns were identified. Patterns suggest that influenza circulation may be dependent on a multitude of factors including seasonality and population movement. Dominant strains in Southeast Asian countries were later detected in other countries. Thus, timely reporting and regional sharing of information about influenza may serve as an early warning, and may assist countries to anticipate the potential severity and burden associated with incoming strains. PMID- 22675428 TI - A meta-analysis of the existing knowledge of immunoreactivity against hepatitis C virus (HCV). AB - Approximately 3% of the world population is infected by HCV, which represents a major global health challenge. Almost 400 different scientific reports present immunological data related to T cell and antibody epitopes derived from HCV literature. Analysis of all HCV-related epitope hosted in the Immune Epitope Database (IEDB), a repository of freely accessible immune epitope data, revealed more than 1500 and 1900 distinct T cell and antibody epitopes, respectively. The inventory of all data revealed specific trends in terms of the host and the HCV genotypes from which sequences were derived. Upon further analysis we found that this large number of epitopes reflects overlapping structures, and homologous sequences derived from different HCV isolates. To access and visualize this information we developed a novel strategy that assembles large sets of epitope data, maps them onto reference genomes and displays the frequency of positive responses. Compilation of the HCV immune reactivity from hundreds of different studies, revealed a complex and thorough picture of HCV immune epitope data to date. The results pinpoint areas of more intense reactivity or research activities at the level of antibody, CD4 and CD8 responses for each of the individual HCV proteins. In general, the areas targeted by the different effector immune functions were distinct and antibody reactivity was positively correlated with hydrophilicity, while T cell reactivity correlated with hydrophobicity. At the sequence level, epitopes frequently recognized by both T cell and B cell correlated with low variability, and our analysis thus highlighted areas of potential interest for practical applications. The human reactivity was further analyzed to pinpoint differential patterns of reactivity associated with acute versus chronic infection, to reveal the apparent impact of glycosylation on T cell, but not antibody responses, and to highlight a paucity of studies involved antibody epitopes associated with virus neutralization. PMID- 22675429 TI - Therapeutic validity and effectiveness of preoperative exercise on functional recovery after joint replacement: a systematic review and meta-analysis. AB - BACKGROUND: Our aim was to develop a rating scale to assess the therapeutic validity of therapeutic exercise programmes. By use of this rating scale we investigated the therapeutic validity of therapeutic exercise in patients awaiting primary total joint replacement (TJR). Finally, we studied the association between therapeutic validity of preoperative therapeutic exercise and its effectiveness in terms of postoperative functional recovery. METHODS: (Quasi) randomised clinical trials on preoperative therapeutic exercise in adults awaiting TJR on postoperative recovery of functioning within three months after surgery were identified through database and reference screening. Two reviewers extracted data and assessed the risk of bias and therapeutic validity. Therapeutic validity of the interventions was assessed with a nine-itemed, expert based rating scale (scores range from 0 to 9; score >=6 reflecting therapeutic validity), developed in a four-round Delphi study. Effects were pooled using a random-effects model and meta-regression was used to study the influence of therapeutic validity. RESULTS: Of the 7,492 articles retrieved, 12 studies (737 patients) were included. None of the included studies demonstrated therapeutic validity and two demonstrated low risk of bias. Therapeutic exercise was not associated with 1) observed functional recovery during the hospital stay (Standardised Mean Difference [SMD]: -1.19; 95%-confidence interval [CI], -2.46 to 0.08); 2) observed recovery within three months of surgery (SMD: -0.15; 95% CI, -0.42 to 0.12); and 3) self-reported recovery within three months of surgery (SMD -0.07; 95%-CI, -0.35 to 0.21) compared with control participants. Meta regression showed no statistically significant relationship between therapeutic validity and pooled-effects. CONCLUSION: Preoperative therapeutic exercise for TJR did not demonstrate beneficial effects on postoperative functional recovery. However, poor therapeutic validity of the therapeutic exercise programmes may have hampered potentially beneficial effects, since none of the studies met the predetermined quality criteria. Future review studies on therapeutic exercise should address therapeutic validity. PMID- 22675430 TI - KRASness and PIK3CAness in patients with advanced colorectal cancer: outcome after treatment with early-phase trials with targeted pathway inhibitors. AB - PURPOSE: To evaluate clinicopathologic and molecular features of patients with metastatic colorectal cancer (mCRC) and their outcomes in early-phase trials using pathway-targeting agents. PATIENTS AND METHODS: We analyzed characteristics of 238 patients with mCRC referred to the phase 1 trials unit at MD Anderson Cancer Center. KRAS, PIK3CA and BRAF status were tested using PCR-based DNA sequencing. RESULTS: Fifty-one percent of patients harbored KRAS mutations; 15% had PIK3CA mutations. In the multivariate regression model for clinical characteristics KRAS mutations were associated with an increased incidence of lung and bone metastases and decreased incidence of adrenal metastases; PIK3CA mutations were marginally correlated with mucinous tumors (p = 0.05). In the univariate analysis, KRAS and PIK3CA mutations were strongly associated. Advanced Duke's stage (p<0.0001) and KRAS mutations (p = 0.01) were the only significant independent predictors of poor survival (Cox proportional hazards model). Patients with PIK3CA mutations had a trend toward shorter progression-free survival when treated with anti-EGFR therapies (p = 0.07). Eighteen of 78 assessable patients (23%) treated with PI3K/Akt/mTOR axis inhibitors achieved stable disease [SD] >=6 months or complete response/partial response (CR/PR), only one of whom were in the subgroup (N = 15) with PIK3CA mutations, perhaps because 10 of these 15 patients (67%) had coexisting KRAS mutations. No SD >=6 months/CR/PR was observed in the 10 patients treated with mitogen-activating protein kinase (MAPK) pathway targeting drugs. CONCLUSIONS: KRAS and PIK3CA mutations frequently coexist in patients with colorectal cancer, and are associated with clinical characteristics and outcome. Overcoming resistance may require targeting both pathways. PMID- 22675431 TI - Lactobacillaceae and cell adhesion: genomic and functional screening. AB - The analysis of collections of lactic acid bacteria (LAB) from traditional fermented plant foods in tropical countries may enable the detection of LAB with interesting properties. Binding capacity is often the main criterion used to investigate the probiotic characteristics of bacteria. In this study, we focused on a collection of 163 Lactobacillaceace comprising 156 bacteria isolated from traditional amylaceous fermented foods and seven strains taken from a collection and used as controls. The collection had a series of analyses to assess binding potential for the selection of new probiotic candidates. The presence/absence of 14 genes involved in binding to the gastrointestinal tract was assessed. This enabled the detection of all the housekeeping genes (ef-Tu, eno, gap, groEl and srtA) in the entire collection, of some of the other genes (apf, cnb, fpbA, mapA, mub) in 86% to 100% of LAB, and of the other genes (cbsA, gtf, msa, slpA) in 0% to 8% of LAB. Most of the bacteria isolated from traditional fermented foods exhibited a genetic profile favorable for their binding to the gastrointestinal tract. We selected 30 strains with different genetic profiles to test their binding ability to non-mucus (HT29) and mucus secreting (HT29-MTX) cell lines as well as their ability to degrade mucus. Assays on both lines revealed high variability in binding properties among the LAB, depending on the cell model used. Finally, we investigated if their binding ability was linked to tighter cross-talk between bacteria and eukaryotic cells by measuring the expression of bacterial genes and of the eukaryotic MUC2 gene. Results showed that wild LAB from tropical amylaceous fermented food had a much higher binding capacity than the two LAB currently known to be probiotics. However their adhesion was not linked to any particular genetic equipment. PMID- 22675432 TI - Acrolein induces endoplasmic reticulum stress and causes airspace enlargement. AB - BACKGROUND: Given the relative abundance and toxic potential of acrolein in inhaled cigarette smoke, it is surprising how little is known about the pulmonary and systemic effects of acrolein. Here we test the hypothesis whether systemic administration of acrolein could cause endoplasmic reticulum (ER) stress, and lung cell apoptosis, leading to the enlargement of the alveolar air spaces in rats. METHODS: Acute and chronic effects of intraperitoneally administered acrolein were tested. Mean alveolar airspace area was measured by using light microscopy and imaging system software. TUNEL staining and immunohistochemistry (IHC) for active caspase 3 and Western blot analysis for active caspase 3, and caspase 12 were performed to detect apoptosis. The ER-stress related gene expression in the lungs was determined by Quantitative real-time PCR analysis. Acrolein-protein adducts in the lung tissue were detected by IHC. RESULTS: Acute administration of acrolein caused a significant elevation of activated caspase 3, upregulation of VEGF expression and induced ER stress proteins in the lung tissue. The chronic administration of acrolein in rats led to emphysematous lung tissue remodeling. TUNEL staining and IHC for cleaved caspase 3 showed a large number of apoptotic septal cells in the acrolein-treated rat lungs. Chronic acrolein administration cause the endoplasmic reticulum stress response manifested by significant upregulation of ATF4, CHOP and GADd34 expression. In smokers with COPD there was a considerable accumulation of acrolein-protein adducts in the inflammatory, airway and vascular cells. CONCLUSIONS: Systemic administration of acrolein causes endoplasmic reticulum stress response, lung cell apoptosis, and chronic administration leads to the enlargement of the alveolar air spaces and emphysema in rats. The substantial accumulation of acrolein-protein adducts in the lungs of COPD patients suggest a role of acrolein in the pathogenesis of emphysema. PMID- 22675433 TI - Transcriptome profiling of citrus fruit response to huanglongbing disease. AB - Huanglongbing (HLB) or "citrus greening" is the most destructive citrus disease worldwide. In this work, we studied host responses of citrus to infection with Candidatus Liberibacter asiaticus (CaLas) using next-generation sequencing technologies. A deep mRNA profile was obtained from peel of healthy and HLB affected fruit. It was followed by pathway and protein-protein network analysis and quantitative real time PCR analysis of highly regulated genes. We identified differentially regulated pathways and constructed networks that provide a deep insight into the metabolism of affected fruit. Data mining revealed that HLB enhanced transcription of genes involved in the light reactions of photosynthesis and in ATP synthesis. Activation of protein degradation and misfolding processes were observed at the transcriptomic level. Transcripts for heat shock proteins were down-regulated at all disease stages, resulting in further protein misfolding. HLB strongly affected pathways involved in source-sink communication, including sucrose and starch metabolism and hormone synthesis and signaling. Transcription of several genes involved in the synthesis and signal transduction of cytokinins and gibberellins was repressed while that of genes involved in ethylene pathways was induced. CaLas infection triggered a response via both the salicylic acid and jasmonic acid pathways and increased the transcript abundance of several members of the WRKY family of transcription factors. Findings focused on the fruit provide valuable insight to understanding the mechanisms of the HLB induced fruit disorder and eventually developing methods based on small molecule applications to mitigate its devastating effects on fruit production. PMID- 22675434 TI - Claudin 1 mediates TNFalpha-induced gene expression and cell migration in human lung carcinoma cells. AB - Epithelial-mesenchymal transition (EMT) is an important mechanism in carcinogenesis. To determine the mechanisms that are involved in the regulation of EMT, it is crucial to develop new biomarkers and therapeutic targets towards cancers. In this study, when TGFbeta1 and TNFalpha were used to induce EMT in human lung carcinoma A549 cells, we found an increase in an epithelial cell tight junction marker, Claudin 1. We further identified that it was the TNFalpha and not the TGFbeta1 that induced the fibroblast-like morphology changes. TNFalpha also caused the increase in Claudin-1 gene expression and protein levels in Triton X-100 soluble cytoplasm fraction. Down-regulation of Claudin-1, using small interfering RNA (siRNA), inhibited 75% of TNFalpha-induced gene expression changes. Claudin-1 siRNA effectively blocked TNFalpha-induced molecular functional networks related to inflammation and cell movement. Claudin-1 siRNA was able to significantly reduce TNF-enhanced cell migration and fibroblast-like morphology. Furthermore, over expression of Claudin 1 with a Claudin 1 pcDNA3.1/V5-His vector enhanced cell migration. In conclusion, these observations indicate that Claudin 1 acts as a critical signal mediator in TNFalpha-induced gene expression and cell migration in human lung cancer cells. Further analyses of these cellular processes may be helpful in developing novel therapeutic strategies. PMID- 22675435 TI - Priority medicines for maternal and child health: a global survey of national essential medicines lists. AB - BACKGROUND: In April 2011, the World Health Organization (WHO) published a list of "priority medicines" for maternal and child health based on 1) the global burden of disease and 2) evidence of efficacy and safety. The objective of this study was to examine the occurrence of these priority medicines on national essential medicines lists. METHODS AND FINDINGS: All essential medicines lists published since 1999 were selected from the WHO website collection. The most-up to date list for each country was then selected, resulting in 89 unique country lists. Each list was evaluated for inclusion of medicines (chemical entity, concentration, and dosage form) on the Priority Medicines List. There was global variation in the listing of the Priority Medicines. The most frequently listed medicine was paracetamol, on 94% (84/89) of lists. Sodium chloride, gentamicin and oral rehydration solution were on 93% (83/89) of lists. The least frequently listed medicine was the children's antimalarial rectal artesunate, on 8% of lists (7/89); artesunate injection was on 16% (14/89) of lists. Pediatric artemisinin combination therapy, as dispersible tablets or flexible oral solid dosage form, appeared on 36% (32/89) of lists. Procaine benzylpenicillin, for treatment of pediatric pneumonia and neonatal sepsis, was on 50% (45/89) of the lists. Zinc, for treatment of diarrhoea in children, was included on only 15% (13/89) of lists. For prevention and treatment of postpartum hemorrhage in women, oxytocin was more prevalent on the lists than misoprostol; they were included on 55 (62%) and 31 (35%) of lists, respectively. Cefixime, for treatment of uncomplicated anogenital gonococcal infection in woman was on 26% (23/89) of lists. Magnesium sulfate injection for treatment of severe pre-eclampsia and eclampsia was on 50% (45/89) of the lists. CONCLUSIONS: The findings suggest that countries need to urgently amend their lists to provide all priority medicines as part of the efforts to improve maternal and child health. PMID- 22675436 TI - A Rickettsiella bacterium from the hard tick, Ixodes woodi: molecular taxonomy combining multilocus sequence typing (MLST) with significance testing. AB - Hard ticks (Acari: Ixodidae) are known to harbour intracellular bacteria from several phylogenetic groups that can develop both mutualistic and pathogenic relationships to the host. This is of particular importance for public health as tick derived bacteria can potentially be transmitted to mammals, including humans, where e.g. Rickettsia or Coxiella act as severe pathogens. Exact molecular taxonomic identification of tick associated prokaryotes is a necessary prerequisite of the investigation of their relationship to both the tick and possible vertebrate hosts. Previously, an intracellular bacterium had been isolated from a monosexual, parthenogenetically reproducing laboratory colony of females of the hard tick, Ixodes woodi Bishopp, and had preliminarily been characterized as a "Rickettsiella-related bacterium". In the present molecular taxonomic study that is based on phylogenetic reconstruction from both 16 S ribosomal RNA and protein-encoding marker sequences complemented with likelihood based significance testing, the bacterium from I. woodi has been identified as a strain of the taxonomic species Rickettsiella grylli. It is the first time that a multilocus sequence typing (MLST) approach based on a four genes comprising MLST scheme has been implemented in order to classify a Rickettsiella-like bacterium to this species. The study demonstrated that MLST holds potential for a better resolution of phylogenetic relationships within the genus Rickettsiella, but requires sequence determination from further Rickettsiella-like bacteria in order to complete the current still fragmentary picture of Rickettsiella systematics. PMID- 22675437 TI - Valence-specific modulation in the accumulation of perceptual evidence prior to visual scene recognition. AB - Visual scene recognition is a dynamic process through which incoming sensory information is iteratively compared with predictions regarding the most likely identity of the input stimulus. In this study, we used a novel progressive unfolding task to characterize the accumulation of perceptual evidence prior to scene recognition, and its potential modulation by the emotional valence of these scenes. Our results show that emotional (pleasant and unpleasant) scenes led to slower accumulation of evidence compared to neutral scenes. In addition, when controlling for the potential contribution of non-emotional factors (i.e., familiarity and complexity of the pictures), our results confirm a reliable shift in the accumulation of evidence for pleasant relative to neutral and unpleasant scenes, suggesting a valence-specific effect. These findings indicate that proactive iterations between sensory processing and top-down predictions during scene recognition are reliably influenced by the rapidly extracted (positive) emotional valence of the visual stimuli. We interpret these findings in accordance with the notion of a genuine positivity offset during emotional scene recognition. PMID- 22675438 TI - Potential markers of aggressive behavior: the fear of other persons' laughter and its overlaps with mental disorders. AB - BACKGROUND: Anecdotal evidence suggested that some outbreaks of aggression and violence may be related to a fear of being laughed at and ridiculed. The present study examined the potential association of the fear of other persons' laughter (gelotophobia) with emotion-related deficits predisposing for aggression, anger and aggression proneness, and its overlaps with relevant mental disorders. METHODOLOGY/PRINCIPAL FINDINGS: Gelotophobic individuals were compared to a non phobic control group with respect to emotion regulation skills and strategies, alexithymia, anger proneness, and aggressive behavior. Social phobia was diagnosed using the Structural Clinical Interview (SCID-I) for DSM IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition). Additionally, the SCID-II modules for Cluster A Personality Disorders, which includes schizoid, paranoid, and schizotypal personality disorder were administered to all participants. The findings show that gelotophobia is associated with deficits in the typical handling of an individual's own affective states, greater anger proneness and more aggressive behavior according to self-report as compared to non-phobic individuals. 80% of the subjects in the gelotophobia group had an additional diagnosis of social phobia and/or Cluster A personality disorder. The additional diagnoses did not predict additional variance of anger or aggressive behavior as compared to gelotophobia alone. CONCLUSIONS/SIGNIFICANCE: Features related to aggression and violence that are inherent in mental disorders such as social phobia and Cluster A personality disorders may be particularly evident in the symptom of fear of other persons' laughter. PMID- 22675439 TI - Complex consequences of herbivory and interplant cues in three annual plants. AB - Information exchange (or signaling) between plants following herbivore damage has recently been shown to affect plant responses to herbivory in relatively simple natural systems. In a large, manipulative field study using three annual plant species (Achyrachaena mollis, Lupinus nanus, and Sinapis arvensis), we tested whether experimental damage to a neighboring conspecific affected a plant's lifetime fitness and interactions with herbivores. By manipulating relatedness between plants, we assessed whether genetic relatedness of neighboring individuals influenced the outcome of having a damaged neighbor. Additionally, in laboratory feeding assays, we assessed whether damage to a neighboring plant specifically affected palatability to a generalist herbivore and, for S. arvensis, a specialist herbivore. Our study suggested a high level of contingency in the outcomes of plant signaling. For example, in the field, damaging a neighbor resulted in greater herbivory to A. mollis, but only when the damaged neighbor was a close relative. Similarly, in laboratory trials, the palatability of S. arvensis to a generalist herbivore increased after the plant was exposed to a damaged neighbor, while palatability to a specialist herbivore decreased. Across all species, damage to a neighbor resulted in decreased lifetime fitness, but only if neighbors were closely related. These results suggest that the outcomes of plant signaling within multi-species neighborhoods may be far more context-specific than has been previously shown. In particular, our study shows that herbivore interactions and signaling between plants are contingent on the genetic relationship between neighboring plants. Many factors affect the outcomes of plant signaling, and studies that clarify these factors will be necessary in order to assess the role of plant information exchange about herbivory in natural systems. PMID- 22675440 TI - Generation of induced pluripotent stem cells from the prairie vole. AB - The vast majority of animals mate more or less promiscuously. A few mammals, including humans, utilize more restrained mating strategies that entail a longer term affiliation with a single mating partner. Such pair bonding mating strategies have been resistant to genetic analysis because of a lack of suitable model organisms. Prairie voles are small mouse-like rodents that form enduring pair bonds in the wild as well as in the laboratory, and consequently they have been used widely to study social bonding behavior. The lack of targeted genetic approaches in this species however has restricted the study of the molecular and neural circuit basis of pair bonds. As a first step in rendering the prairie vole amenable to reverse genetics, we have generated induced pluripotent stem cell (IPSC) lines from prairie vole fibroblasts using retroviral transduction of reprogramming factors. These IPSC lines display the cellular and molecular hallmarks of IPSC cells from other organisms, including mice and humans. Moreover, the prairie vole IPSC lines have pluripotent differentiation potential since they can give rise to all three germ layers in tissue culture and in vivo. These IPSC lines can now be used to develop conditions that facilitate homologous recombination and eventually the generation of prairie voles bearing targeted genetic modifications to study the molecular and neural basis of pair bond formation. PMID- 22675441 TI - Rhizobium promotes non-legumes growth and quality in several production steps: towards a biofertilization of edible raw vegetables healthy for humans. AB - The biofertilization of crops with plant-growth-promoting microorganisms is currently considered as a healthy alternative to chemical fertilization. However, only microorganisms safe for humans can be used as biofertilizers, particularly in vegetables that are raw consumed, in order to avoid sanitary problems derived from the presence of pathogenic bacteria in the final products. In the present work we showed that Rhizobium strains colonize the roots of tomato and pepper plants promoting their growth in different production stages increasing yield and quality of seedlings and fruits. Our results confirmed those obtained in cereals and alimentary oil producing plants extending the number of non-legumes susceptible to be biofertilized with rhizobia to those whose fruits are raw consumed. This is a relevant conclusion since safety of rhizobia for human health has been demonstrated after several decades of legume inoculation ensuring that they are optimal bacteria for biofertilization. PMID- 22675442 TI - Tumor necrosis factor alpha inhibits expression of the iron regulating hormone hepcidin in murine models of innate colitis. AB - BACKGROUND: Abnormal expression of the liver peptide hormone hepcidin, a key regulator of iron homeostasis, contributes to the pathogenesis of anemia in conditions such as inflammatory bowel disease (IBD). Since little is known about the mechanisms that control hepcidin expression during states of intestinal inflammation, we sought to shed light on this issue using mouse models. METHODOLOGY/PRINCIPAL FINDINGS: Hepcidin expression was evaluated in two types of intestinal inflammation caused by innate immune activation-dextran sulfate sodium (DSS)-induced colitis in wild-type mice and the spontaneous colitis occurring in T-bet/Rag2-deficient (TRUC) mice. The role of tumor necrosis factor (TNF) alpha was investigated by in vivo neutralization, and by treatment of a hepatocyte cell line, as well as mice, with the recombinant cytokine. Expression and activation of Smad1, a positive regulator of hepcidin transcription, were assessed during colitis and following administration or neutralization of TNFalpha. Hepcidin expression progressively decreased with time during DSS colitis, correlating with changes in systemic iron distribution. TNFalpha inhibited hepcidin expression in cultured hepatocytes and non-colitic mice, while TNFalpha neutralization during DSS colitis increased it. Similar results were obtained in TRUC mice. These effects involved a TNFalpha-dependent decrease in Smad1 protein but not mRNA. CONCLUSIONS/SIGNIFICANCE: TNFalpha inhibits hepcidin expression in two distinct types of innate colitis, with down-regulation of Smad1 protein playing an important role in this process. This inhibitory effect of TNFalpha may be superseded by other factors in the context of T cell-mediated colitis given that in the latter form of intestinal inflammation hepcidin is usually up-regulated. PMID- 22675443 TI - Transcriptional profiling of human brain endothelial cells reveals key properties crucial for predictive in vitro blood-brain barrier models. AB - Brain microvascular endothelial cells (BEC) constitute the blood-brain barrier (BBB) which forms a dynamic interface between the blood and the central nervous system (CNS). This highly specialized interface restricts paracellular diffusion of fluids and solutes including chemicals, toxins and drugs from entering the brain. In this study we compared the transcriptome profiles of the human immortalized brain endothelial cell line hCMEC/D3 and human primary BEC. We identified transcriptional differences in immune response genes which are directly related to the immortalization procedure of the hCMEC/D3 cells. Interestingly, astrocytic co-culturing reduced cell adhesion and migration molecules in both BECs, which possibly could be related to regulation of immune surveillance of the CNS controlled by astrocytic cells within the neurovascular unit. By matching the transcriptome data from these two cell lines with published transcriptional data from freshly isolated mouse BECs, we discovered striking differences that could explain some of the limitations of using cultured BECs to study BBB properties. Key protein classes such as tight junction proteins, transporters and cell surface receptors show differing expression profiles. For example, the claudin-5, occludin and JAM2 expression is dramatically reduced in the two human BEC lines, which likely explains their low transcellular electric resistance and paracellular leakiness. In addition, the human BEC lines express low levels of unique brain endothelial transporters such as Glut1 and Pgp. Cell surface receptors such as LRP1, RAGE and the insulin receptor that are involved in receptor-mediated transport are also expressed at very low levels. Taken together, these data illustrate that BECs lose their unique protein expression pattern outside of their native environment and display a more generic endothelial cell phenotype. A collection of key genes that seems to be highly regulated by the local surroundings of BEC within the neurovascular unit are presented and discussed. PMID- 22675444 TI - Genetic control of a central pattern generator: rhythmic oromotor movement in mice is controlled by a major locus near Atp1a2. AB - Fluid licking in mice is a rhythmic behavior that is controlled by a central pattern generator (CPG) located in a complex of brainstem nuclei. C57BL/6J (B6) and DBA/2J (D2) strains differ significantly in water-restricted licking, with a highly heritable difference in rates (h(2)>=0.62) and a corresponding 20% difference in interlick interval (mean +/- SEM = 116.3+/-1 vs 95.4+/-1.1 ms). We systematically quantified motor output in these strains, their F(1) hybrids, and a set of 64 BXD progeny strains. The mean primary interlick interval (MPI) varied continuously among progeny strains. We detected a significant quantitative trait locus (QTL) for a CPG controlling lick rate on Chr 1 (Lick1), and a suggestive locus on Chr 10 (Lick10). Linkage was verified by testing of B6.D2-1D congenic stock in which a segment of Chr 1 of the D2 strain was introgressed onto the B6 parent. The Lick1 interval on distal Chr 1 contains several strong candidate genes. One of these is a sodium/potassium pump subunit (Atp1a2) with widespread expression in astrocytes, as well as in a restricted population of neurons. Both this subunit and the entire Na(+)/K(+)-ATPase molecule have been implicated in rhythmogenesis for respiration and locomotion. Sequence variants in or near Apt1a2 strongly modulate expression of the cognate mRNA in multiple brain regions. This gene region has recently been sequenced exhaustively and we have cataloged over 300 non-coding and synonymous mutations segregating among BXD strains, one or more of which is likely to contribute to differences in central pattern generator tempo. PMID- 22675445 TI - Effect of levels of acetate on the mevalonate pathway of Borrelia burgdorferi. AB - Borrelia burgdorferi, the agent of Lyme disease, is a spirochetal pathogen with limited metabolic capabilities that survives under highly disparate host-specific conditions. However, the borrelial genome encodes several proteins of the mevalonate pathway (MP) that utilizes acetyl-CoA as a substrate leading to intermediate metabolites critical for biogenesis of peptidoglycan and post translational modifications of proteins. In this study, we analyzed the MP and contributions of acetate in modulation of adaptive responses in B. burgdorferi. Reverse-transcription PCR revealed that components of the MP are transcribed as individual open reading frames. Immunoblot analysis using monospecific sera confirmed synthesis of members of the MP in B. burgdorferi. The rate-limiting step of the MP is mediated by HMG-CoA reductase (HMGR) via conversion of HMG-CoA to mevalonate. Recombinant borrelial HMGR exhibited a K(m) value of 132 uM with a V(max) of 1.94 umol NADPH oxidized minute(-1) (mg protein)(-1) and was inhibited by statins. Total protein lysates from two different infectious, clonal isolates of B. burgdorferi grown under conditions that mimicked fed-ticks (pH 6.8/37 degrees C) exhibited increased levels of HMGR while other members of the MP were elevated under unfed-tick (pH 7.6/23 degrees C) conditions. Increased extra cellular acetate gave rise to elevated levels of MP proteins along with RpoS, CsrA(Bb) and their respective regulons responsible for mediating vertebrate host specific adaptation. Both lactone and acid forms of two different statins inhibited growth of B. burgdorferi strain B31, while overexpression of HMGR was able to partially overcome that inhibition. In summary, these studies on MP and contributions of acetate to host-specific adaptation have helped identify potential metabolic targets that can be manipulated to reduce the incidence of Lyme disease. PMID- 22675447 TI - High-throughput construction of intron-containing hairpin RNA vectors for RNAi in plants. AB - With the wide use of double-stranded RNA interference (RNAi) for the analysis of gene function in plants, a high-throughput system for making hairpin RNA (hpRNA) constructs is in great demand. Here, we describe a novel restriction-ligation approach that provides a simple but efficient construction of intron-containing hpRNA (ihpRNA) vectors. The system takes advantage of the type IIs restriction enzyme BsaI and our new plant RNAi vector pRNAi-GG based on the Golden Gate (GG) cloning. This method requires only a single PCR product of the gene of interest flanked with BsaI recognition sequence, which can then be cloned into pRNAi-GG at both sense and antisense orientations simultaneously to form ihpRNA construct. The process, completed in one tube with one restriction-ligation step, produced a recombinant ihpRNA with high efficiency and zero background. We demonstrate the utility of the ihpRNA constructs generated with pRNAi-GG vector for the effective silencing of various individual endogenous and exogenous marker genes as well as two genes simultaneously. This method provides a novel and high-throughput platform for large-scale analysis of plant functional genomics. PMID- 22675446 TI - Colorectal cancer linkage on chromosomes 4q21, 8q13, 12q24, and 15q22. AB - A substantial proportion of familial colorectal cancer (CRC) is not a consequence of known susceptibility loci, such as mismatch repair (MMR) genes, supporting the existence of additional loci. To identify novel CRC loci, we conducted a genome wide linkage scan in 356 white families with no evidence of defective MMR (i.e., no loss of tumor expression of MMR proteins, no microsatellite instability (MSI) high tumors, or no evidence of linkage to MMR genes). Families were ascertained via the Colon Cancer Family Registry multi-site NCI-supported consortium (Colon CFR), the City of Hope Comprehensive Cancer Center, and Memorial University of Newfoundland. A total of 1,612 individuals (average 5.0 per family including 2.2 affected) were genotyped using genome-wide single nucleotide polymorphism linkage arrays; parametric and non-parametric linkage analysis used MERLIN in a priori defined family groups. Five lod scores greater than 3.0 were observed assuming heterogeneity. The greatest were among families with mean age of diagnosis less than 50 years at 4q21.1 (dominant HLOD = 4.51, alpha = 0.84, 145.40 cM, rs10518142) and among all families at 12q24.32 (dominant HLOD = 3.60, alpha = 0.48, 285.15 cM, rs952093). Among families with four or more affected individuals and among clinic-based families, a common peak was observed at 15q22.31 (101.40 cM, rs1477798; dominant HLOD = 3.07, alpha = 0.29; dominant HLOD = 3.03, alpha = 0.32, respectively). Analysis of families with only two affected individuals yielded a peak at 8q13.2 (recessive HLOD = 3.02, alpha = 0.51, 132.52 cM, rs1319036). These previously unreported linkage peaks demonstrate the continued utility of family-based data in complex traits and suggest that new CRC risk alleles remain to be elucidated. PMID- 22675448 TI - Genomic analysis of immune response against Vibrio cholerae hemolysin in Caenorhabditis elegans. AB - Vibrio cholerae cytolysin (VCC) is among the accessory V. cholerae virulence factors that may contribute to disease pathogenesis in humans. VCC, encoded by hlyA gene, belongs to the most common class of bacterial toxins, known as pore forming toxins (PFTs). V. cholerae infects and kills Caenorhabditis elegans via cholerae toxin independent manner. VCC is required for the lethality, growth retardation and intestinal cell vacuolation during the infection. However, little is known about the host gene expression responses against VCC. To address this question we performed a microarray study in C. elegans exposed to V. cholerae strains with intact and deleted hlyA genes.Many of the VCC regulated genes identified, including C-type lectins, Prion-like (glutamine [Q]/asparagine [N] rich)-domain containing genes, genes regulated by insulin/IGF-1-mediated signaling (IIS) pathway, were previously reported as mediators of innate immune response against other bacteria in C. elegans. Protective function of the subset of the genes up-regulated by VCC was confirmed using RNAi. By means of a machine learning algorithm called FastMEDUSA, we identified several putative VCC induced immune regulatory transcriptional factors and transcription factor binding motifs. Our results suggest that VCC is a major virulence factor, which induces a wide variety of immune response- related genes during V. cholerae infection in C. elegans. PMID- 22675449 TI - Prospective study of rape perpetration by young South African men: incidence & risk factors. AB - BACKGROUND: There has been very little prospective research on rape perpetration among men. This paper describes the incidence and risk factors for new rape and attempted rape events among young South African men in an HIV prevention trial. METHODS: We followed 1,147 men aged 15-26 years who enrolled into a cluster randomised controlled trial to evaluate the HIV prevention behavioural intervention Stepping Stones. Incidence rate ratios for factors associated with incident rape were derived from Poisson models. RESULTS: The young men reported 217 incident rapes (completed or attempted) of a girl or woman over 1,914 person years of follow up, yielding a rape incidence of 11.2 per 100 person years. Overall 24.9% of men had previously raped at baseline, and 18.9% did so during the follow up. Among the latter, 61.3% raped for the first time, and 38.7% re offended. Multivariable Poisson modelling showed a higher incidence of rape perpetration among men who had ever used drugs (IRR 1.86 95%CI 1.39, 2.49), had eight or more lifetime partners (IRR 1.48 95% CI 1.09, 2.01), had been physically violent toward a female partner (IRR 1.50 95%CI 1.11, 2.03) and had disclosed rape perpetration at baseline (IRR 1.45 95%CI 1.07, 1.97). A lower incidence was found among those with greater resistance to peer pressure (IRR 0.85 95%CI 0.74, 0.97). CONCLUSIONS: The findings highlight the importance of male gender socialisation and addressing delinquent youth sub-cultures in rape prevention. Prevention requires change in hegemonic masculinity, with its emphasis on gender hierarchy, exaggerated performance of heterosexuality and control of women. Interventions are needed to address male socialisation with delinquent peers, by reducing exposure to childhood trauma and strengthening opportunities for gainful employment (in work or recreation). PMID- 22675450 TI - Association of glomerular filtration rate with high-sensitivity cardiac troponin T in a community-based population study in Beijing. AB - BACKGROUND: Reduced renal function is an independent risk factor for cardiovascular disease mortality, and persistently elevated cardiac troponin T (cTnT) is frequently observed in patients with end-stage renal disease. In the general population the relationship between renal function and cTnT levels may not be clear because of the low sensitivity of the assay. In this study, we investigated the level of cTnT using a highly sensitive assay (hs-cTnT) and evaluated the association of estimated glomerular filtration rate (eGFR) with detectable hs-cTnT levels in a community-based population. METHODS: The serum hs cTnT levels were measured in 1365 community dwelling population aged >=45 years in Beijing, China. eGFR was determined by the Chinese modifying modification of diet in renal disease (C-MDRD) equation. RESULTS: With the highly sensitive assay, cTnT levels were detectable (>=3pg/mL) in 744 subjects (54.5%). The result showed that eGFR was associated with Log hs-cTnT (r = -0.14, P<0.001). After adjustment for the high predicted Framingham Coronary Heart Disease (CHD) risk (10-year risk >20%) and other prognostic indicators, moderate to severe reduced eGFR was independently associated with detectable hs-cTnT, whereas normal to mildly reduced eGFR was not independently associated with detectable hs-cTnT. In addition, after adjustment for other risk factors, the high predicted Framingham CHD risk was associated with detectable hs-cTnT in the subjects with different quartile levels of eGFR. CONCLUSION: The levels of hs-cTnT are detectable in a community-based Chinese population and low eGFR is associated with detectable hs cTnT. Moreover, eGFR and high predicted Framingham CHD risk are associated with detectable hs-cTnT in subjects with moderate-to-severe reduced renal function. PMID- 22675451 TI - p38MAPK, ERK and PI3K signaling pathways are involved in C5a-primed neutrophils for ANCA-mediated activation. AB - BACKGROUND: The complement system is one of the important contributing factors in the development of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). C5a and the neutrophil C5a receptor play a central role in antineutrophil cytoplasmic antibody (ANCA)-mediated neutrophil recruitment and activation. The current study further investigated the signaling pathways of C5a mediated priming of human neutrophils for ANCA-induced neutrophil activation. METHODOLOGY/PRINCIPAL FINDINGS: The effects of the p38 mitogen-activated protein kinase (p38MAPK) inhibitor (SB202190), extracellular signal-regulated kinase (ERK) inhibitor (PD98059), c-Jun N-terminal kinase (JNK) inhibitor (6o) and phosphoinositol 3-kinase (PI3K) inhibitor (LY294002) were tested on respiratory burst and degranulation of C5a-primed neutrophils activated with ANCA, as well as on C5a-induced increase in expression of membrane-bound PR3 (mPR3) on neutrophils. For C5a-primed neutrophils for MPO-ANCA-induced respiratory burst, the mean fluorescence intensity (MFI) value was 254.8+/-67.1, which decreased to 203.6+/-60.3, 204.4+/-36.7, 202.4+/-49.9 and 188+/-47.9 upon pre-incubation with SB202190, PD98059, LY294002 and the mixture of above-mentioned three inhibitors (compared with that without inhibitors, P<0.01, P<0.05, P<0.01 and P<0.05), respectively. For PR3-ANCA-positive IgG, the MFI value increased in C5a-primed neutrophils, which decreased upon pre-incubation with above-mentioned inhibitors. The lactoferrin concentration increased in C5a-primed neutrophils induced by MPO or PR3-ANCA-positive IgG supernatant and decreased upon pre-incubation with above mentioned three inhibitors. mPR3 expression increased from 923.3+/-182.4 in untreated cells to 1278.3+/-299.3 after C5a treatment and decreased to 1069.9+/ 188.9, 1100+/-238.2, 1092.3+/-231.8 and 1053.9+/-200.3 by SB202190, PD98059, LY294002 and the mixture of above-mentioned three inhibitors (compared with that without inhibitors, P<0.01, P<0.05, P<0.01 and P<0.01), respectively. CONCLUSIONS/SIGNIFICANCE: Activation of p38MAPK, ERK and PI3K are important steps in the translocation of ANCA antigens and C5a-induced activation of neutrophils by ANCA. PMID- 22675452 TI - Importance of GluA1 subunit-containing AMPA glutamate receptors for morphine state-dependency. AB - In state-dependency, information retrieval is most efficient when the animal is in the same state as it was during the information acquisition. State-dependency has been implicated in a variety of learning and memory processes, but its mechanisms remain to be resolved. Here, mice deficient in AMPA-type glutamate receptor GluA1 subunits were first conditioned to morphine (10 or 20 mg/kg s.c. during eight sessions over four days) using an unbiased procedure, followed by testing for conditioned place preference at morphine states that were the same as or different from the one the mice were conditioned to. In GluA1 wildtype littermate mice the same-state morphine dose produced the greatest expression of place preference, while in the knockout mice no place preference was then detected. Both wildtype and knockout mice expressed moderate morphine-induced place preference when not at the morphine state (saline treatment at the test); in this case, place preference was weaker than that in the same-state test in wildtype mice. No correlation between place preference scores and locomotor activity during testing was found. Additionally, as compared to the controls, the knockout mice showed unchanged sensitization to morphine, morphine drug discrimination and brain regional MU-opioid receptor signal transduction at the G protein level. However, the knockout mice failed to show increased AMPA/NMDA receptor current ratios in the ventral tegmental area dopamine neurons of midbrain slices after a single injection of morphine (10 mg/kg, s.c., sliced prepared 24 h afterwards), in contrast to the wildtype mice. The results indicate impaired drug-induced state-dependency in GluA1 knockout mice, correlating with impaired opioid-induced glutamate receptor neuroplasticity. PMID- 22675453 TI - A proton leak current through the cardiac sodium channel is linked to mixed arrhythmia and the dilated cardiomyopathy phenotype. AB - Cardiac Na(+) channels encoded by the SCN5A gene are essential for initiating heart beats and maintaining a regular heart rhythm. Mutations in these channels have recently been associated with atrial fibrillation, ventricular arrhythmias, conduction disorders, and dilated cardiomyopathy (DCM).We investigated a young male patient with a mixed phenotype composed of documented conduction disorder, atrial flutter, and ventricular tachycardia associated with DCM. Further family screening revealed DCM in the patient's mother and sister and in three of the mother's sisters. Because of the complex clinical phenotypes, we screened SCN5A and identified a novel mutation, R219H, which is located on a highly conserved region on the fourth helix of the voltage sensor domain of Na(v)1.5. Three family members with DCM carried the R219H mutation.The wild-type (WT) and mutant Na(+) channels were expressed in a heterologous expression system, and intracellular pH (pHi) was measured using a pH-sensitive electrode. The biophysical characterization of the mutant channel revealed an unexpected selective proton leak with no effect on its biophysical properties. The H(+) leak through the mutated Na(v)1.5 channel was not related to the Na(+) permeation pathway but occurred through an alternative pore, most probably a proton wire on the voltage sensor domain.We propose that acidification of cardiac myocytes and/or downstream events may cause the DCM phenotype and other electrical problems in affected family members. The identification of this clinically significant H(+) leak may lead to the development of more targeted treatments. PMID- 22675454 TI - Kruppel-like factor 5 protects against murine colitis and activates JAK-STAT signaling in vivo. AB - Inflammatory bowel disease (IBD), which is characterized by chronic or recurring inflammation of the gastrointestinal tract, affects 1.4 million persons in the United States alone. KLF5, a Kruppel-like factor (KLF) family member, is expressed within the epithelia of the gastrointestinal tract and has been implicated in rapid cell proliferation, migration, and remodeling in a number of tissues. Given these functions, we hypothesized that constitutive Klf5 expression would protect against the development of colitis in vivo. To examine the role of KLF5 in vivo, we used the Villin promoter to target Klf5 to the entire horizontal axis of the small intestine and colon. Villin-Klf5 transgenic mice were born at normal Mendelian ratios and appeared grossly normal to at least 1 year of age. Surprisingly, there were no significant changes in cell proliferation or in the differentiation of any of the intestinal lineages within the duodenum, jejunum, ileum, and colon of Villin-Klf5 mice, compared to littermate controls. However, when Villin-Klf5 mice were treated with dextran sodium sulfate (DSS) to induce colitis, they developed less colonic injury and significantly reduced disease activity scores than littermate controls. The mechanism for this decreased injury may come via JAK-STAT signaling, the activation of which was increased in colonic mucosa of DSS treated Villin-Klf5 mice compared to controls. Thus, KLF5 and its downstream mediators may provide therapeutic targets and disease markers for IBD or other diseases characterized by injury and disruption of intestinal epithelia. PMID- 22675455 TI - Introduction of environmentally degradable parameters to evaluate the biodegradability of biodegradable polymers. AB - Environmentally Degradable Parameter ((Ed)K) is of importance in the describing of biodegradability of environmentally biodegradable polymers (BDPs). In this study, a concept (Ed)K was introduced. A test procedure of using the ISO 14852 method and detecting the evolved carbon dioxide as an analytical parameter was developed, and the calculated (Ed)K was used as an indicator for the ultimate biodegradability of materials. Starch and polyethylene used as reference materials were defined as the (Ed)K values of 100 and 0, respectively. Natural soil samples were inoculated into bioreactors, followed by determining the rates of biodegradation of the reference materials and 15 commercial BDPs over a 2-week test period. Finally, a formula was deduced to calculate the value of (Ed)K for each material. The (Ed)K values of the tested materials have a positive correlation to their biodegradation rates in the simulated soil environment, and they indicated the relative biodegradation rate of each material among all the tested materials. Therefore, the (Ed)K was shown to be a reliable indicator for quantitatively evaluating the potential biodegradability of BDPs in the natural environment. PMID- 22675456 TI - Situational awareness of influenza activity based on multiple streams of surveillance data using multivariate dynamic linear model. AB - BACKGROUND: Multiple sources of influenza surveillance data are becoming more available; however integration of these data streams for situational awareness of influenza activity is less explored. METHODS AND RESULTS: We applied multivariate time-series methods to sentinel outpatient and school absenteeism surveillance data in Hong Kong during 2004-2009. School absenteeism data and outpatient surveillance data experienced interruptions due to school holidays and changes in public health guidelines during the pandemic, including school closures and the establishment of special designated flu clinics, which in turn provided 'drop-in' fever counts surveillance data. A multivariate dynamic linear model was used to monitor influenza activity throughout epidemics based on all available data. The inferred level followed influenza activity closely at different times, while the inferred trend was less competent with low influenza activity. Correlations between inferred level and trend from the multivariate model and reference influenza activity, measured by the product of weekly laboratory influenza detection rates and weekly general practitioner influenza-like illness consultation rates, were calculated and compared with those from univariate models. Over the whole study period, there was a significantly higher correlation (rho = 0.82, p<=0.02) for the inferred trend based on the multivariate model compared to other univariate models, while the inferred trend from the multivariate model performed as well as the best univariate model in the pre pandemic and the pandemic period. The inferred trend and level from the multivariate model was able to match, if not outperform, the best univariate model albeit with missing data plus drop-in and drop-out of different surveillance data streams. An overall influenza index combining level and trend was constructed to demonstrate another potential use of the method. CONCLUSIONS: Our results demonstrate the potential use of multiple streams of influenza surveillance data to promote situational awareness about the level and trend of seasonal and pandemic influenza activity. PMID- 22675457 TI - Inhibition of specific NF-kappaB activity contributes to the tumor suppressor function of 14-3-3sigma in breast cancer. AB - 14-3-3sigma is frequently lost in human breast cancers by genetic deletion or promoter methylation. We have now investigated the involvement of 14-3-3sigma in the termination of NF-kappaB signal in mammary cells and its putative role in cancer relapse and metastasis. Our results show that 14-3-3sigma regulates nuclear export of p65-NF-kappaB following chronic TNFalpha stimulation. Restoration of 14-3-3sigma in breast cancer cells reduces migration capacity and metastatic abilities in vivo. By microarray analysis, we have identified a genetic signature that responds to TNFalpha in a 14-3-3sigma-dependent manner and significantly associates with different breast and other types of cancer. By interrogating public databases, we have found that over-expression of this signature correlates with poor relapse-free survival in breast cancer patients. Finally, screening of 96 human breast tumors showed that NF-kappaB activation strictly correlates with the absence of 14-3-3sigma and it is significantly associated with worse prognosis in the multivariate analysis. Our findings identify a genetic signature that is important for breast cancer prognosis and for future personalized treatments based on NF-kappaB targeting. PMID- 22675458 TI - Performance of repetitive tasks induces decreased grip strength and increased fibrogenic proteins in skeletal muscle: role of force and inflammation. AB - BACKGROUND: This study elucidates exposure-response relationships between performance of repetitive tasks, grip strength declines, and fibrogenic-related protein changes in muscles, and their link to inflammation. Specifically, we examined forearm flexor digitorum muscles for changes in connective tissue growth factor (CTGF; a matrix protein associated with fibrosis), collagen type I (Col1; a matrix component), and transforming growth factor beta 1 (TGFB1; an upstream modulator of CTGF and collagen), in rats performing one of two repetitive tasks, with or without anti-inflammatory drugs. METHODOLOGY/RESULTS: To examine the roles of force versus repetition, rats performed either a high repetition negligible force food retrieval task (HRNF), or a high repetition high force handle-pulling task (HRHF), for up to 9 weeks, with results compared to trained only (TR-NF or TR-HF) and normal control rats. Grip strength declined with both tasks, with the greatest declines in 9-week HRHF rats. Quantitative PCR (qPCR) analyses of HRNF muscles showed increased expression of Col1 in weeks 3-9, and CTGF in weeks 6 and 9. Immunohistochemistry confirmed PCR results, and also showed greater increases of CTGF and collagen matrix in 9-week HRHF rats than 9 week HRNF rats. ELISA, and immunohistochemistry revealed greater increases of TGFB1 in TR-HF and 6-week HRHF, compared to 6-week HRNF rats. To examine the role of inflammation, results from 6-week HRHF rats were compared to rats receiving ibuprofen or anti-TNF-alpha treatment in HRHF weeks 4-6. Both treatments attenuated HRHF-induced increases in CTGF and fibrosis by 6 weeks of task performance. Ibuprofen attenuated TGFB1 increases and grip strength declines, matching our prior results with anti-TNFalpha. CONCLUSIONS/SIGNIFICANCE: Performance of highly repetitive tasks was associated with force-dependent declines in grip strength and increased fibrogenic-related proteins in flexor digitorum muscles. These changes were attenuated, at least short-term, by anti inflammatory treatments. PMID- 22675459 TI - Transactivation of EGFR by LPS induces COX-2 expression in enterocytes. AB - Necrotizing enterocolitis (NEC) is the leading cause of gastrointestinal morbidity and mortality in preterm infants. NEC is characterized by an exaggerated inflammatory response to bacterial flora leading to bowel necrosis. Bacterial lipopolysaccharide (LPS) mediates inflammation through TLR4 activation and is a key molecule in the pathogenesis of NEC. However, LPS also induces cyclooxygenase-2 (COX-2), which promotes intestinal barrier restitution through stimulation of intestinal cell survival, proliferation, and migration. Epidermal growth factor receptor (EGFR) activation prevents experimental NEC and may play a critical role in LPS-stimulated COX-2 production. We hypothesized that EGFR is required for LPS induction of COX-2 expression. Our data show that inhibiting EGFR kinase activity blocks LPS-induced COX-2 expression in small intestinal epithelial cells. LPS induction of COX-2 requires Src-family kinase signaling while LPS transactivation of EGFR requires matrix metalloprotease (MMP) activity. EGFR tyrosine kinase inhibitors block LPS stimulation of mitogen-activated protein kinase ERK, suggesting an important role of the MAPK/ERK pathway in EGFR mediated COX-2 expression. LPS stimulates proliferation of IEC-6 cells, but this stimulation is inhibited with either the EGFR kinase inhibitor AG1478, or the selective COX-2 inhibitor Celecoxib. Taken together, these data show that EGFR plays an important role in LPS-induction of COX-2 expression in enterocytes, which may be one mechanism for EGF in inhibition of NEC. PMID- 22675460 TI - Healthy lifestyle and leukocyte telomere length in U.S. women. AB - CONTEXT: Whether a healthy lifestyle may be associated with longer telomere length is largely unknown. OBJECTIVES: To examine healthy lifestyle practices, which are primary prevention measures against major age-related chronic diseases, in relation to leukocyte telomere length. DESIGN AND SETTING: Cross-sectional analysis in the Nurses' Health Study (NHS). PARTICIPANTS: The population consisted of 5,862 women who participated in multiple prospective case-control studies within the NHS cohort. Z scores of leukocyte telomere length were derived within each case-control study. Based on prior work, we defined low-risk or healthy categories for five major modifiable factors assessed in 1988 or 1990: non-current smoking, maintaining a healthy body weight (body mass index in 18.5 24.9 kg/m(2)), engaging in regular moderate or vigorous physical activities (>=150 minutes/week), drinking alcohol in moderation (1 drink/week to <2 drinks/day), and eating a healthy diet (Alternate Healthy Eating Index score in top 50%). We calculated difference (%) of the z scores contrasting low-risk groups with reference groups to evaluate the association of interest. RESULTS: Although none of the individual low-risk factors was significantly associated with larger leukocyte telomere length z scores, we observed a significant, positive relationship between the number of low-risk factors and the z scores. In comparison with women who had zero low-risk factors (1.9% of the total population) and were, therefore, considered the least healthy group, the leukocyte telomere length z scores were 16.4%, 22.1%, 28.7%, 22.6%, and 31.2% (P for trend = 0.015) higher for women who had 1 to 5 low-risk factors, respectively. CONCLUSIONS: Adherence to a healthy lifestyle, defined by major modifiable risk factors, was associated with longer telomere length in leukocytes. PMID- 22675461 TI - Staphylococcus aureus surface protein SdrE binds complement regulator factor H as an immune evasion tactic. AB - Similar to other highly successful invasive bacterial pathogens, Staphylococcus aureus recruits the complement regulatory protein factor H (fH) to its surface to inhibit the alternative pathway of complement. Here, we report the identification of the surface-associated protein SdrE as a fH-binding protein using purified fH overlay of S. aureus fractionated cell wall proteins and fH cross-linking to S. aureus followed by mass spectrometry. Studies using recombinant SdrE revealed that rSdrE bound significant fH whether from serum or as a purified form, in both a time- and dose-dependent manner. Furthermore, rSdrE-bound fH exhibited cofactor functionality for factor I (fI)-mediated cleavage of C3b to iC3b which correlated positively with increasing amounts of fH. Expression of SdrE on the surface of the surrogate bacterium Lactococcus lactis enhanced recruitment of fH which resulted in increased iC3b generation. Moreover, surface expression of SdrE led to a reduction in C3-fragment deposition, less C5a generation, and reduced killing by polymorphonuclear cells. Thus, we report the first identification of a S. aureus protein associated with the staphylococcal surface that binds factor H as an immune evasion mechanism. PMID- 22675462 TI - Prevalence of abnormalities in vestibular function and balance among HIV seropositive and HIV-seronegative women and men. AB - BACKGROUND: Most HIV-seropositive subjects in western countries receive highly active antiretroviral therapy (HAART). Although many aspects of their health have been studied, little is known about their vestibular and balance function. The goals of this study were to determine the prevalences of vestibular and balance impairments among HIV-seropositive and comparable seronegative men and women and to determine if those groups differed. METHODS: Standard screening tests of vestibular and balance function, including head thrusts, Dix-Hallpike maneuvers, and Romberg balance tests on compliant foam were performed during semiannual study visits of participants who were enrolled in the Baltimore and Washington, D. C. sites of the Multicenter AIDS Cohort Study and the Women's Interagency HIV Study. RESULTS: No significant differences by HIV status were found on most tests, but HIV-seropositive subjects who were using HAART had a lower frequency of abnormal Dix-Hallpike nystagmus than HIV-seronegative subjects. A significant number of nonclassical Dix-Hallpike responses were found. Age was associated with Romberg scores on foam with eyes closed. Sex was not associated with any of the test scores. CONCLUSION: These findings suggest that HAART-treated HIV infection has no harmful association with vestibular function in community-dwelling, ambulatory men and women. The association with age was expected, but the lack of association with sex was unexpected. The presence of nonclassical Dix-Hallpike responses might be consistent with central nervous system lesions. PMID- 22675464 TI - Monitoring and scoring counter-diffusion protein crystallization experiments in capillaries by in situ dynamic light scattering. AB - In this paper, we demonstrate the feasibility of using in situ Dynamic Light Scattering (DLS) to monitor counter-diffusion crystallization experiments in capillaries. Firstly, we have validated the quality of the DLS signal in thin capillaries, which is comparable to that obtained in standard quartz cuvettes. Then, we have carried out DLS measurements of a counter-diffusion crystallization experiment of glucose isomerase in capillaries of different diameters (0.1, 0.2 and 0.3 mm) in order to follow the temporal evolution of protein supersaturation. Finally, we have compared DLS data with optical recordings of the progression of the crystallization front and with a simulation model of counter-diffusion in 1D. PMID- 22675463 TI - Fundamentals of FGF19 & FGF21 action in vitro and in vivo. AB - Fibroblast growth factors 19 (FGF19) and 21 (FGF21) have emerged as key regulators of energy metabolism. Several studies have been conducted to understand the mechanism of FGF19 and FGF21 action, however, the data presented has often been inconsistent and at times contradictory. Here in a single study we compare the mechanisms mediating FGF19/FGF21 actions, and how similarities/differences in actions at the cellular level between these two factors translate to common/divergent physiological outputs. Firstly, we show that in cell culture FGF19/FGF21 are very similar, however, key differences are still observed differentiating the two. In vitro we found that both FGF's activate FGFRs in the context of betaKlotho (KLB) expression. Furthermore, both factors alter ERK phosphorylation and glucose uptake with comparable potency. Combination treatment of cells with both factors did not have additive effects and treatment with a competitive inhibitor, the FGF21 delta N17 mutant, also blocked FGF19's effects, suggestive of a shared receptor activation mechanism. The key differences between FGF21/FGF19 were noted at the receptor interaction level, specifically the unique ability of FGF19 to bind/signal directly via FGFR4. To determine if differential effects on energy homeostasis and hepatic mitogenicity exist we treated DIO and ob/ob mice with FGF19/FGF21. We find comparable efficacy of the two proteins to correct body weight and serum glucose in both DIO and ob/ob mice. Nevertheless, FGF21 and FGF19 had distinctly different effects on proliferation in the liver. Interestingly, in vivo blockade of FGF21 signaling in mice using DeltaN17 caused profound changes in glycemia indicative of the critical role KLB and FGF21 play in the regulation of glucose homeostasis. Overall, our data demonstrate that while subtle differences exist in vitro the metabolic effects in vivo of FGF19/FGF21 are indistinguishable, supporting a shared mechanism of action for these two hormones in the regulation of energy balance. PMID- 22675466 TI - Reversible induction of phantom auditory sensations through simulated unilateral hearing loss. AB - Tinnitus, a phantom auditory sensation, is associated with hearing loss in most cases, but it is unclear if hearing loss causes tinnitus. Phantom auditory sensations can be induced in normal hearing listeners when they experience severe auditory deprivation such as confinement in an anechoic chamber, which can be regarded as somewhat analogous to a profound bilateral hearing loss. As this condition is relatively uncommon among tinnitus patients, induction of phantom sounds by a lesser degree of auditory deprivation could advance our understanding of the mechanisms of tinnitus. In this study, we therefore investigated the reporting of phantom sounds after continuous use of an earplug. 18 healthy volunteers with normal hearing wore a silicone earplug continuously in one ear for 7 days. The attenuation provided by the earplugs simulated a mild high frequency hearing loss, mean attenuation increased from <10 dB at 0.25 kHz to >30 dB at 3 and 4 kHz. 14 out of 18 participants reported phantom sounds during earplug use. 11 participants presented with stable phantom sounds on day 7 and underwent tinnitus spectrum characterization with the earplug still in place. The spectra showed that the phantom sounds were perceived predominantly as high pitched, corresponding to the frequency range most affected by the earplug. In all cases, the auditory phantom disappeared when the earplug was removed, indicating a causal relation between auditory deprivation and phantom sounds. This relation matches the predictions of our computational model of tinnitus development, which proposes a possible mechanism by which a stabilization of neuronal activity through homeostatic plasticity in the central auditory system could lead to the development of a neuronal correlate of tinnitus when auditory nerve activity is reduced due to the earplug. PMID- 22675465 TI - Nucleolin inhibits G4 oligonucleotide unwinding by Werner helicase. AB - BACKGROUND: The Werner protein (WRNp), a member of the RecQ helicase family, is strongly associated with the nucleolus, as is nucleolin (NCL), an important nucleolar constituent protein. Both WRNp and NCL respond to the effects of DNA damaging agents. Therefore, we have investigated if these nuclear proteins interact and if this interaction has a possible functional significance in DNA damage repair. METHODOLOGY/PRINCIPAL FINDINGS: Here we report that WRNp interacts with the RNA-binding protein, NCL, based on immunoprecipitation, immunofluorescent co-localization in live and fixed cells, and direct binding of purified WRNp to nucleolin. We also map the binding region to the C-terminal domains of both proteins. Furthermore, treatment of U2OS cells with 15 uM of the Topoisomerase I inhibitor, camptothecin, causes the dissociation of the nucleolin Werner complex in the nucleolus, followed by partial re-association in the nucleoplasm. Other DNA damaging agents, such as hydroxyurea, Mitomycin C, and aphidicolin do not have these effects. Nucleolin or its C-terminal fragment affected the helicase, but not the exonuclease activity of WRNp, by inhibiting WRN unwinding of G4 tetraplex DNA structures, as seen in activity assays and electrophoretic mobility shift assays (EMSA). CONCLUSIONS/SIGNIFICANCE: These data suggest that nucleolin may regulate G4 DNA unwinding by WRNp, possibly in response to certain DNA damaging agents. We postulate that the NCL-WRNp complex may contain an inactive form of WRNp, which is released from the nucleolus upon DNA damage. Then, when required, WRNp is released from inhibition and can participate in the DNA repair processes. PMID- 22675467 TI - Fundamental limits on wavelength, efficiency and yield of the charge separation triad. AB - In an attempt to optimize a high yield, high efficiency artificial photosynthetic protein we have discovered unique energy and spatial architecture limits which apply to all light-activated photosynthetic systems. We have generated an analytical solution for the time behavior of the core three cofactor charge separation element in photosynthesis, the photosynthetic cofactor triad, and explored the functional consequences of its makeup including its architecture, the reduction potentials of its components, and the absorption energy of the light absorbing primary-donor cofactor. Our primary findings are two: First, that a high efficiency, high yield triad will have an absorption frequency more than twice the reorganization energy of the first electron transfer, and second, that the relative distance of the acceptor and the donor from the primary-donor plays an important role in determining the yields, with the highest efficiency, highest yield architecture having the light absorbing cofactor closest to the acceptor. Surprisingly, despite the increased complexity found in natural solar energy conversion proteins, we find that the construction of this central triad in natural systems matches these predictions. Our analysis thus not only suggests explanations for some aspects of the makeup of natural photosynthetic systems, it also provides specific design criteria necessary to create high efficiency, high yield artificial protein-based triads. PMID- 22675468 TI - Functional characterization of CLPTM1L as a lung cancer risk candidate gene in the 5p15.33 locus. AB - Cleft Lip and Palate Transmembrane Protein 1-Like (CLPTM1L), resides in a region of chromosome 5 for which copy number gain has been found to be the most frequent genetic event in the early stages of non-small cell lung cancer (NSCLC). This locus has been found by multiple genome wide association studies to be associated with lung cancer in both smokers and non-smokers. CLPTM1L has been identified as an overexpressed protein in human ovarian tumor cell lines that are resistant to cisplatin, which is the only insight thus far into the function of CLPTM1L. Here we find CLPTM1L expression to be increased in lung adenocarcinomas compared to matched normal lung tissues and in lung tumor cell lines by mechanisms not exclusive to copy number gain. Upon loss of CLPTM1L accumulation in lung tumor cells, cisplatin and camptothecin induced apoptosis were increased in direct proportion to the level of CLPTM1L knockdown. Bcl-xL accumulation was significantly decreased upon loss of CLPTM1L. Expression of exogenous Bcl-xL abolished sensitization to apoptotic killing with CLPTM1L knockdown. These results demonstrate that CLPTM1L, an overexpressed protein in lung tumor cells, protects from genotoxic stress induced apoptosis through regulation of Bcl-xL. Thus, this study implicates anti-apoptotic CLPTM1L function as a potential mechanism of susceptibility to lung tumorigenesis and resistance to chemotherapy. PMID- 22675469 TI - Quantitative RT-PCR profiling of the rabbit immune response: assessment of acute Shigella flexneri infection. AB - Quantitative reverse transcription PCR analysis is an important tool to monitor changes in gene expression in animal models. The rabbit is a widely accepted and commonly used animal model in the study of human diseases and infections by viral, fungal, bacterial and protozoan pathogens. Only a limited number of rabbit genes have, however, been analyzed by this method as the rabbit genome sequence remains unfinished. Recently, increasing coverage of the genome has permitted the prediction of a growing number of genes that are relevant in the context of the immune response. We hereby report the design of twenty-four quantitative PCR primer pairs covering common cytokines, chemoattractants, antimicrobials and enzymes for a rapid, sensitive and quantitative analysis of the rabbit immune response. Importantly, all primer pairs were designed to be used under identical experimental conditions, thereby enabling the simultaneous analysis of all genes in a high-throughput format. This tool was used to analyze the rabbit innate immune response to infection with the human gastrointestinal pathogen Shigella flexneri. Beyond the known inflammatory mediators, we identified IL-22, IL-17A and IL-17F as highly upregulated cytokines and as first responders to infection during the innate phase of the host immune response. This set of qPCR primers also provides a convenient tool for monitoring the rabbit immune response during infection with other pathogens and other inflammatory conditions. PMID- 22675470 TI - Monitoring an alien invasion: DNA barcoding and the identification of lionfish and their prey on coral reefs of the Mexican Caribbean. AB - BACKGROUND: In the Mexican Caribbean, the exotic lionfish Pterois volitans has become a species of great concern because of their predatory habits and rapid expansion onto the Mesoamerican coral reef, the second largest continuous reef system in the world. This is the first report of DNA identification of stomach contents of lionfish using the barcode of life reference database (BOLD). METHODOLOGY/PRINCIPAL FINDINGS: We confirm with barcoding that only Pterois volitans is apparently present in the Mexican Caribbean. We analyzed the stomach contents of 157 specimens of P. volitans from various locations in the region. Based on DNA matches in the Barcode of Life Database (BOLD) and GenBank, we identified fishes from five orders, 14 families, 22 genera and 34 species in the stomach contents. The families with the most species represented were Gobiidae and Apogonidae. Some prey taxa are commercially important species. Seven species were new records for the Mexican Caribbean: Apogon mosavi, Coryphopterus venezuelae, C. thrix, C. tortugae, Lythrypnus minimus, Starksia langi and S. ocellata. DNA matches, as well as the presence of intact lionfish in the stomach contents, indicate some degree of cannibalism, a behavior confirmed in this species by the first time. We obtained 45 distinct crustacean prey sequences, from which only 20 taxa could be identified from the BOLD and GenBank databases. The matches were primarily to Decapoda but only a single taxon could be identified to the species level, Euphausia americana. CONCLUSIONS/SIGNIFICANCE: This technique proved to be an efficient and useful method, especially since prey species could be identified from partially-digested remains. The primary limitation is the lack of comprehensive coverage of potential prey species in the region in the BOLD and GenBank databases, especially among invertebrates. PMID- 22675471 TI - LSDP5 enhances triglyceride storage in hepatocytes by influencing lipolysis and fatty acid beta-oxidation of lipid droplets. AB - Lipid storage droplet protein 5 (LSDP5) is a lipid droplet-associated protein of the PAT (perilipin, adipophilin, and TIP47) family that is expressed in the liver in a peroxisome proliferator-activated receptor alpha (PPARalpha)-dependent manner; however, its exact function has not been elucidated. We noticed that LSDP5 was localized to the surface of lipid droplets in hepatocytes. Overexpression of LSDP5 enhanced lipid accumulation in the hepatic cell line AML12 and in primary hepatocytes. Knock-down of LSDP5 significantly decreased the triglyceride content of lipid droplets, stimulated lipolysis, and modestly increased the mitochondrial content and level of fatty-acid beta-oxidation in the mitochondria. The expression of PPARalpha was increased in LSDP5-deficient cells and required for the increase in the level of fatty acid beta-oxidation in LSDP5 deficient cells. Using serial deletions of LSDP5, we determined that the lipid droplet-targeting domain and the domain directing lipid droplet clustering overlapped and were localized to the 188 amino acid residues at the N-terminus of LSDP5. Our findings suggest that LSDP5, a novel lipid droplet protein, may contribute to triglyceride accumulation by negatively regulating lipolysis and fatty acid oxidation in hepatocytes. PMID- 22675472 TI - Protein phosphatase-1alpha interacts with and dephosphorylates polycystin-1. AB - Polycystin signaling is likely to be regulated by phosphorylation. While a number of potential protein kinases and their target phosphorylation sites on polycystin 1 have been identified, the corresponding phosphatases have not been extensively studied. We have now determined that polycystin-1 is a regulatory subunit for protein phosphatase-1alpha (PP1alpha). Sequence analysis has revealed the presence of a highly conserved PP1-interaction motif in the cytosolic, C-terminal tail of polycystin-1; and we have shown that transfected PP1alpha specifically co immunoprecipitates with a polycystin-1 C-tail construct. To determine whether PP1alpha dephosphorylates polycystin-1, a PKA-phosphorylated GST-polycystin-1 fusion protein was shown to be dephosphorylated by PP1alpha but not by PP2B (calcineurin). Mutations within the PP1-binding motif of polycystin-1, including an autosomal dominant polycystic kidney disease (ADPKD)-associated mutation, significantly reduced PP1alpha-mediated dephosphorylation of polycystin-1. The results suggest that polycystin-1 forms a holoenzyme complex with PP1alpha via a conserved PP1-binding motif within the polycystin-1 C-tail, and that PKA phosphorylated polycystin-1 serves as a substrate for the holoenzyme. PMID- 22675473 TI - Epicoccum nigrum P16, a sugarcane endophyte, produces antifungal compounds and induces root growth. AB - BACKGROUND: Sugarcane is one of the most important crops in Brazil, mainly because of its use in biofuel production. Recent studies have sought to determine the role of sugarcane endophytic microbial diversity in microorganism-plant interactions, and their biotechnological potential. Epicoccum nigrum is an important sugarcane endophytic fungus that has been associated with the biological control of phytopathogens, and the production of secondary metabolites. In spite of several studies carried out to define the better conditions to use E. nigrum in different crops, little is known about the establishment of an endophytic interaction, and its potential effects on plant physiology. METHODOLOGY/PRINCIPAL FINDINGS: We report an approach based on inoculation followed by re-isolation, molecular monitoring, microscopic analysis, plant growth responses to fungal colonization, and antimicrobial activity tests to study the basic aspects of the E. nigrum endophytic interaction with sugarcane, and the effects of colonization on plant physiology. The results indicate that E. nigrum was capable of increasing the root system biomass and producing compounds that inhibit the in vitro growth of sugarcane pathogens Fusarium verticillioides, Colletotrichum falcatum, Ceratocystis paradoxa, and Xanthomomas albilineans. In addition, E. nigrum preferentially colonizes the sugarcane surface and, occasionally, the endophytic environment. CONCLUSIONS/SIGNIFICANCE: Our work demonstrates that E. nigrum has great potential for sugarcane crop application because it is capable of increasing the root system biomass and controlling pathogens. The study of the basic aspects of the interaction of E. nigrum with sugarcane demonstrated the facultative endophytism of E. nigrum and its preference for the phylloplane environment, which should be considered in future studies of biocontrol using this species. In addition, this work contributes to the knowledge of the interaction of this ubiquitous endophyte with the host plant, and also to a better use of microbial endophytes in agriculture. PMID- 22675474 TI - Effects of marine reserves versus nursery habitat availability on structure of reef fish communities. AB - No-take marine fishery reserves sustain commercial stocks by acting as buffers against overexploitation and enhancing fishery catches in adjacent areas through spillover. Likewise, nursery habitats such as mangroves enhance populations of some species in adjacent habitats. However, there is lack of understanding of the magnitude of stock enhancement and the effects on community structure when both protection from fishing and access to nurseries concurrently act as drivers of fish population dynamics. In this study we test the separate as well as interactive effects of marine reserves and nursery habitat proximity on structure and abundance of coral reef fish communities. Reserves had no effect on fish community composition, while proximity to nursery habitat only had a significant effect on community structure of species that use mangroves or seagrass beds as nurseries. In terms of reef fish biomass, proximity to nursery habitat by far outweighed (biomass 249% higher than that in areas with no nursery access) the effects of protection from fishing in reserves (biomass 21% lower than non reserve areas) for small nursery fish (<= 25 cm total length). For large-bodied individuals of nursery species (>25 cm total length), an additive effect was present for these two factors, although fish benefited more from fishing protection (203% higher biomass) than from proximity to nurseries (139% higher). The magnitude of elevated biomass for small fish on coral reefs due to proximity to nurseries was such that nursery habitats seem able to overrule the usually positive effects on fish biomass by reef reserves. As a result, conservation of nursery habitats gains importance and more consideration should be given to the ecological processes that occur along nursery-reef boundaries that connect neighboring ecosystems. PMID- 22675475 TI - Disulfide bridges remain intact while native insulin converts into amyloid fibrils. AB - Amyloid fibrils are beta-sheet-rich protein aggregates commonly found in the organs and tissues of patients with various amyloid-associated diseases. Understanding the structural organization of amyloid fibrils can be beneficial for the search of drugs to successfully treat diseases associated with protein misfolding. The structure of insulin fibrils was characterized by deep ultraviolet resonance Raman (DUVRR) and Nuclear Magnetic Resonance (NMR) spectroscopy combined with hydrogen-deuterium exchange. The compositions of the fibril core and unordered parts were determined at single amino acid residue resolution. All three disulfide bonds of native insulin remained intact during the aggregation process, withstanding scrambling. Three out of four tyrosine residues were packed into the fibril core, and another aromatic amino acid, phenylalanine, was located in the unordered parts of insulin fibrils. In addition, using all-atom MD simulations, the disulfide bonds were confirmed to remain intact in the insulin dimer, which mimics the fibrillar form of insulin. PMID- 22675476 TI - Immunogenicity of self-associated aggregates and chemically cross-linked conjugates of the 42 kDa Plasmodium falciparum merozoite surface protein-1. AB - Self-associated protein aggregates or cross-linked protein conjugates are, in general, more immunogenic than oligomeric or monomeric forms. In particular, the immunogenicity in mice of a recombinant malaria transmission blocking vaccine candidate, the ookinete specific Plasmodium falciparum 25 kDa protein (Pfs25), was increased more than 1000-fold when evaluated as a chemical cross-linked protein-protein conjugate as compared to a formulated monomer. Whether alternative approaches using protein complexes improve the immunogenicity of other recombinant malaria vaccine candidates is worth assessing. In this work, the immunogenicity of the recombinant 42 kDa processed form of the P. falciparum merozoite surface protein 1 (MSP1(42)) was evaluated as a self-associated, non covalent aggregate and as a chemical cross-linked protein-protein conjugate to ExoProtein A, which is a recombinant detoxified form of Pseudomonas aeruginosa exotoxin A. MSP1(42) conjugates were prepared and characterized biochemically and biophysically to determine their molar mass in solution and stoichiometry, when relevant. The immunogenicity of the MSP1(42) self-associated aggregates, cross linked chemical conjugates and monomers were compared in BALB/c mice after adsorption to aluminum hydroxide adjuvant, and in one instance in association with the TLR9 agonist CPG7909 with an aluminum hydroxide formulation. Antibody titers were assessed by ELISA. Unlike observations made for Pfs25, no significant enhancement in MSP1(42) specific antibody titers was observed for any conjugate as compared to the formulated monomer or dimer, except for the addition of the TLR9 agonist CPG7909. Clearly, enhancing the immunogenicity of a recombinant protein vaccine candidate by the formation of protein complexes must be established on an empirical basis. PMID- 22675477 TI - Situationally-sensitive knowledge translation and relational decision making in hyperacute stroke: a qualitative study. AB - Stroke is a leading cause of disability. Early treatment of acute ischaemic stroke with rtPA reduces the risk of longer term dependency but carries an increased risk of causing immediate bleeding complications. To understand the challenges of knowledge translation and decision making about treatment with rtPA in hyperacute stroke and hence to inform development of appropriate decision support we interviewed patients, their family and health professionals. The emergency setting and the symptomatic effects of hyper-acute stroke shaped the form, content and manner of knowledge translation to support decision making. Decision making about rtPA in hyperacute stroke presented three conundrums for patients, family and clinicians. 1) How to allow time for reflection in a severely time-limited setting. 2) How to facilitate knowledge translation regarding important treatment risks and benefits when patient and family capacity is blunted by the effects and shock of stroke. 3) How to ensure patient and family views are taken into account when the situation produces reliance on the expertise of clinicians. Strategies adopted to meet these conundrums were fourfold: face to face communication; shaping decisions; incremental provision of information; and communication tailored to the individual patient. Relational forms of interaction were understood to engender trust and allay anxiety. Shaping decisions with patients was understood as an expression of confidence by clinicians that helped alleviate anxiety and offered hope and reassurance to patients and their family experiencing the shock of the stroke event. Neutral presentations of information and treatment options promoted uncertainty and contributed to anxiety. 'Drip feeding' information created moments for reflection: clinicians literally made time. Tailoring information to the particular patient and family situation allowed clinicians to account for social and emotional contexts. The principal responses to the challenges of decision making about rtPA in hyperacute stroke were relational decision support and situationally-sensitive knowledge translation. PMID- 22675478 TI - Analysis and functional consequences of increased Fab-sialylation of intravenous immunoglobulin (IVIG) after lectin fractionation. AB - It has been proposed that the anti-inflammatory effects of intravenous immunoglobulin (IVIG) might be due to the small fraction of Fc-sialylated IgG. In this study we biochemically and functionally characterized sialic acid-enriched IgG obtained by Sambucus nigra agglutinin (SNA) lectin fractionation. Two main IgG fractions isolated by elution with lactose (E1) or acidified lactose (E2) were analyzed for total IgG, F(ab')(2) and Fc-specific sialic acid content, their pattern of specific antibodies and anti-inflammatory potential in a human in vitro inflammation system based on LPS- or PHA-stimulated whole blood. HPLC and LC-MS testing revealed an increase of sialylated IgG in E1 and more substantially in the E2 fraction. Significantly, the increased amount of sialic acid residues was primarily found in the Fab region whereas only a minor increase was observed in the Fc region. This indicates preferential binding of the Fab sialic acid to SNA. ELISA analyses of a representative range of pathogen and auto-antigens indicated a skewed antibody pattern of the sialylated IVIG fractions. Finally, the E2 fraction exerted a more profound anti-inflammatory effect compared to E1 or IVIG, evidenced by reduced CD54 expression on monocytes and reduced secretion of MCP-1 (CCL2); again these effects were Fab- but not Fc-dependent. Our results show that SNA fractionation of IVIG yields a minor fraction (approx. 10%) of highly sialylated IgG, wherein the sialic acid is mainly found in the Fab region. The tested anti-inflammatory activity was associated with Fab not Fc sialylation. PMID- 22675479 TI - Do characteristics of faces that convey trustworthiness and dominance underlie perceptions of criminality? AB - BACKGROUND: This study tested whether the 2D face evaluation model proposed by Oosterhof and Todorov can parsimoniously account for why some faces are perceived as more criminal-looking than others. The 2D model proposes that trust and dominance are spontaneously evaluated from features of faces. These evaluations have adaptive significance from an evolutionary standpoint because they indicate whether someone should be approached or avoided. METHOD: Participants rated the emotional state, personality traits, and criminal appearance of faces shown in photographs. The photographs were of males and females taken under naturalistic conditions (i.e., police mugshots) and highly controlled conditions. In the controlled photographs, the emotion display of the actor was systematically varied (happy expression, emotionally neutral expression, or angry expression). RESULTS: Both male and female faces rated high in criminal appearance were perceived as less trustworthy and more dominant in police mugshots as well as in photographs taken under highly controlled conditions. Additionally, emotionally neutral faces were deemed as less trustworthy if they were perceived as angry, and more dominant if they were morphologically mature. Systematically varying emotion displays also affected criminality ratings, with angry faces perceived as the most criminal, followed by neutral faces and then happy faces. CONCLUSION: The 2D model parsimoniously accounts for criminality perceptions. This study extends past research by demonstrating that morphological features that signal high dominance and low trustworthiness can also signal high criminality. Spontaneous evaluations regarding criminal propensity may have adaptive value in that they may help us to avoid someone who is physically threatening. On the other hand, such evaluations could inappropriately influence decision making in criminal identification lineups. Hence, additional research is needed to discover whether and how people can avoid making evaluations regarding criminality from a person's facial appearance. PMID- 22675480 TI - Selective reduction of AMPA currents onto hippocampal interneurons impairs network oscillatory activity. AB - Reduction of excitatory currents onto GABAergic interneurons in the forebrain results in impaired spatial working memory and altered oscillatory network patterns in the hippocampus. Whether this phenotype is caused by an alteration in hippocampal interneurons is not known because most studies employed genetic manipulations affecting several brain regions. Here we performed viral injections in genetically modified mice to ablate the GluA4 subunit of the AMPA receptor in the hippocampus (GluA4(HC-/-) mice), thereby selectively reducing AMPA receptor mediated currents onto a subgroup of hippocampal interneurons expressing GluA4. This regionally selective manipulation led to a strong spatial working memory deficit while leaving reference memory unaffected. Ripples (125-250 Hz) in the CA1 region of GluA4(HC-/-) mice had larger amplitude, slower frequency and reduced rate of occurrence. These changes were associated with an increased firing rate of pyramidal cells during ripples. The spatial selectivity of hippocampal pyramidal cells was comparable to that of controls in many respects when assessed during open field exploration and zigzag maze running. However, GluA4 ablation caused altered modulation of firing rate by theta oscillations in both interneurons and pyramidal cells. Moreover, the correlation between the theta firing phase of pyramidal cells and position was weaker in GluA4(HC-/-) mice. These results establish the involvement of AMPA receptor-mediated currents onto hippocampal interneurons for ripples and theta oscillations, and highlight potential cellular and network alterations that could account for the altered working memory performance. PMID- 22675481 TI - Sympatric spawning but allopatric distribution of Anguilla japonica and Anguilla marmorata: temperature- and oceanic current-dependent sieving. AB - Anguilla japonica and Anguilla marmorata share overlapping spawning sites, similar drifting routes, and comparable larval durations. However, they exhibit allopatric geographical distributions in East Asia. To clarify this ecological discrepancy, glass eels from estuaries in Taiwan, the Philippines, Indonesia, and China were collected monthly, and the survival rate of A. marmorata under varying water salinities and temperatures was examined. The composition ratio of these 2 eel species showed a significant latitude cline, matching the 24 degrees C sea surface temperature isotherm in winter. Both species had opposing temperature preferences for recruitment. A. marmorata prefer high water temperatures and die at low water temperatures. In contrast, A. japonica can endure low water temperatures, but their recruitment is inhibited by high water temperatures. Thus, A. japonica glass eels, which mainly spawn in summer, are preferably recruited to Taiwan, China, Korea, and Japan by the Kuroshio and its branch waters in winter. Meanwhile, A. marmorata glass eels, which spawn throughout the year, are mostly screened out in East Asia in areas with low-temperature coastal waters in winter. During summer, the strong northward currents from the South China Sea and Changjiang River discharge markedly block the Kuroshio invasion and thus restrict the approach of A. marmorata glass eels to the coasts of China and Korea. The differences in the preferences of the recruitment temperature for glass eels combined with the availability of oceanic currents shape the real geographic distribution of Anguilla japonica and Anguilla marmorata, making them "temperate" and "tropical" eels, respectively. PMID- 22675482 TI - On the mechanism of action of SJ-172550 in inhibiting the interaction of MDM4 and p53. AB - SJ-172550 (1) was previously discovered in a biochemical high throughput screen for inhibitors of the interaction of MDMX and p53 and characterized as a reversible inhibitor (J. Biol. Chem. 2010; 285:10786). Further study of the biochemical mode of action of 1 has shown that it acts through a complicated mechanism in which the compound forms a covalent but reversible complex with MDMX and locks MDMX into a conformation that is unable to bind p53. The relative stability of this complex is influenced by many factors including the reducing potential of the media, the presence of aggregates, and other factors that influence the conformational stability of the protein. This complex mechanism of action hinders the further development of compound 1 as a selective MDMX inhibitor. PMID- 22675483 TI - An efficient rank based approach for closest string and closest substring. AB - This paper aims to present a new genetic approach that uses rank distance for solving two known NP-hard problems, and to compare rank distance with other distance measures for strings. The two NP-hard problems we are trying to solve are closest string and closest substring. For each problem we build a genetic algorithm and we describe the genetic operations involved. Both genetic algorithms use a fitness function based on rank distance. We compare our algorithms with other genetic algorithms that use different distance measures, such as Hamming distance or Levenshtein distance, on real DNA sequences. Our experiments show that the genetic algorithms based on rank distance have the best results. PMID- 22675484 TI - Comparative analysis on the key enzymes of the glycerol cycle metabolic pathway in Dunaliella salina under osmotic stresses. AB - The glycerol metabolic pathway is a special cycle way; glycerol-3-phosphate dehydrogenase (G3pdh), glycerol-3-phosphate phosphatase (G3pp), dihydroxyacetone reductase (Dhar), and dihydroxyacetone kinase (Dhak) are the key enzymes around the pathway. Glycerol is an important osmolyte for Dunaliella salina to resist osmotic stress. In this study, comparative activities of the four enzymes in D. salina and their activity changes under various salt stresses were investigated, from which glycerol metabolic flow direction in the glycerol metabolic pathway was estimated. Results showed that the salinity changes had different effects on the enzymes activities. NaCl could stimulate the activities of all the four enzymes in various degrees when D. salina was grown under continuous salt stress. When treated by hyperosmotic or hypoosmotic shock, only the activity of G3pdh in D. salina was significantly stimulated. It was speculated that, under osmotic stresses, the emergency response of the cycle pathway in D. salina was driven by G3pdh via its response to the osmotic stress. Subsequently, with the changes of salinity, other three enzymes started to respond to osmotic stress. Dhar played a role of balancing the cycle metabolic pathway by its forward and backward reactions. Through synergy, the four enzymes worked together for the effective flow of the cycle metabolic pathways to maintain the glycerol requirements of cells in order to adapt to osmotic stress environments. PMID- 22675485 TI - Habitat association and seasonality in a mosaic and bimodal hybrid zone between Chorthippus brunneus and C. jacobsi (Orthoptera: Acrididae). AB - Understanding why some hybrid zones are bimodal and others unimodal can aid in identifying barriers to gene exchange following secondary contact. The hybrid zone between the grasshoppers Chorthippus brunneus and C. jacobsi contains a mix of allopatric parental populations and inter-mingled bimodal and unimodal sympatric populations, and provides an ideal system to examine the roles of local selection and gene flow between populations in maintaining bimodality. However, it is first necessary to confirm, over a larger spatial scale, previously identified associations between population composition and season and habitat. Here we use cline-fitting of one morphological and one song trait along two valley transects, and intervening mountains, to confirm previously identified habitat associations (mountain versus valley) and seasonal changes in population composition. As expected from previous findings of studies on a smaller spatial scale, C. jacobsi dominated mountain habitats and mixed populations dominated valleys, and C. brunneus became more prevalent in August. Controlling for habitat and incorporating into the analysis seasonal changes in cline parameters and the standard errors of parental trait values revealed wider clines than previous studies (best estimates of 6.4 to 24.5 km in our study versus 2.8 to 4.7 km in previous studies) and increased percentage of trait variance explained (52.7% and 61.5% for transects 1 and 2 respectively, versus 17.6%). Revealing such strong and consistent patterns within a complex hybrid zone will allow more focused examination of the causes of variation in bimodality in mixed populations, in particular the roles of local selection versus habitat heterogeneity and gene flow between differentiated populations. PMID- 22675486 TI - Adults scan own- and other-race faces differently. AB - It is well established that individuals show an other-race effect (ORE) in face recognition: they recognize own-race faces better than other-race faces. The present study tested the hypothesis that individuals would also scan own- and other-race faces differently. We asked Chinese participants to remember Chinese and Caucasian faces and we tested their memory of the faces over five testing blocks. The participants' eye movements were recorded with the use of an eye tracker. The data were analyzed with an Area of Interest approach using the key AOIs of a face (eyes, nose, and mouth). Also, we used the iMap toolbox to analyze the raw data of participants' fixation on each pixel of the entire face. Results from both types of analyses strongly supported the hypothesis. When viewing target Chinese or Caucasian faces, Chinese participants spent a significantly greater proportion of fixation time on the eyes of other-race Caucasian faces than the eyes of own-race Chinese faces. In contrast, they spent a significantly greater proportion of fixation time on the nose and mouth of Chinese faces than the nose and mouth of Caucasian faces. This pattern of differential fixation, for own- and other-race eyes and nose in particular, was consistent even as participants became increasingly familiar with the target faces of both races. The results could not be explained by the perceptual salience of the Chinese nose or Caucasian eyes because these features were not differentially salient across the races. Our results are discussed in terms of the facial morphological differences between Chinese and Caucasian faces and the enculturation of mutual gaze norms in East Asian cultures. PMID- 22675487 TI - Transthoracic resection versus non-transthoracic resection for gastroesophageal junction cancer: a meta-analysis. AB - BACKGROUND: The aim of this meta-analysis is to evaluate the impact of transthoracic resection on long-term survival of patients with GEJ cancer and to compare the postoperative morbidity and mortality of patients undergoing transthoracic resection with those of patients who were not undergoing transthoracic resection. METHOD: Searches of electronic databases identifying studies from Medline, Cochrane Library trials register, and WHO Trial Registration etc were performed. Outcome measures were survival, postoperative morbidity and mortality, and operation related events. RESULTS: Twelve studies (including 5 RCTs and 7 non-RCTs) comprising 1105 patients were included in this meta-analysis, with 591 patients assigned treatment with transthoracic resection. Transthoracic resection did not increase the 5-y overall survival rate for RCTs and non-RCTs (HR = 1.01, 95% CI 0.80- 1.29 and HR = 0.89, 95% CI 0.70- 1.14, respectively). Stratified by the Siewert classification, our result showed no obvious differences were observed between the group with transthoracic resection and group without transthoracic resection (P>0.05). The postoperative morbidity (RR = 0.69, 95% CI 0.48- 1.00 and OR = 0.55, 95% CI 0.25- 1.22) and mortality (RD = -0.03, 95% CI -0.06- 0.00 and RD = 0.00, 95% CI -0.05- 0.05) of RCTs and non RCTs did not suggest any significant differences between the two groups. Hospital stay was long with thransthoracic resection (WMD = -5.80, 95% CI -10.38- -1.23) but did not seem to differ in number of harvested lymph nodes, operation time, blood loss, numbers of patients needing transfusion, and reoperation rate. The results of sensitivity analyses were similar to the primary analyses. CONCLUSIONS: There were no significant differences of survival rate and postoperative morbidity and mortality between transthoracic resection group and non-transthoracic resection group. Both surgical approaches are acceptable, and that one offers no clear advantage over the other. However, the results should be interpreted cautiously since the qualities of included studies were suboptimal. PMID- 22675488 TI - Aflatoxin-induced TP53 R249S mutation in hepatocellular carcinoma in Thailand: association with tumors developing in the absence of liver cirrhosis. AB - Primary Liver Cancer (PLC) is the leading cause of death by cancer among males in Thailand and the 3(rd) among females. Most cases are hepatocellular carcinoma (HCC) but cholangiocarcinomas represent between 4 and 80% of liver cancers depending upon geographic area. Most HCC are associated with chronic infection by Hepatitis B Virus while a G -> T mutation at codon 249 of the TP53 gene, R249S, specific for exposure to aflatoxin, is detected in tumors for up to 30% of cases. We have used Short Oligonucleotide Mass Analysis (SOMA) to quantify free circulating R249S-mutated DNA in plasma using blood specimens collected in a hospital case:control study. Plasma R249S-mutated DNA was detectable at low concentrations (>= 67 copies/mL) in 53 to 64% of patients with primary liver cancer or chronic liver disease and in 19% of controls. 44% of patients with HCC and no evidence of cirrhosis had plasma concentrations of R249S-mutated DNA >= 150 copies/mL, compared to 21% in patients with both HCC and cirrhosis, 22% in patients with cholangiocarcinoma, 12% in patients with non-cancer chronic liver disease and 3% of subjects in the reference group. Thus, plasma concentrations of R249S-mutated DNA >= 150 copies/mL tended to be more common in patients with HCC developing without pre-existing cirrhosis (p = 0.027). Overall, these results support the preferential occurrence of R249S-mutated DNA in HCC developing in the absence of cirrhosis in a context of HBV chronic infection. PMID- 22675489 TI - Adult human brain neural progenitor cells (NPCs) and fibroblast-like cells have similar properties in vitro but only NPCs differentiate into neurons. AB - The ability to culture neural progenitor cells from the adult human brain has provided an exciting opportunity to develop and test potential therapies on adult human brain cells. To achieve a reliable and reproducible adult human neural progenitor cell (AhNPC) culture system for this purpose, this study fully characterized the cellular composition of the AhNPC cultures, as well as the possible changes to this in vitro system over prolonged culture periods. We isolated cells from the neurogenic subventricular zone/hippocampus (SVZ/HP) of the adult human brain and found a heterogeneous culture population comprised of several types of post-mitotic brain cells (neurons, astrocytes, and microglia), and more importantly, two distinct mitotic cell populations; the AhNPCs, and the fibroblast-like cells (FbCs). These two populations can easily be mistaken for a single population of AhNPCs, as they both proliferate under AhNPC culture conditions, form spheres and express neural progenitor cell and early neuronal markers, all of which are characteristics of AhNPCs in vitro. However, despite these similarities under proliferating conditions, under neuronal differentiation conditions, only the AhNPCs differentiated into functional neurons and glia. Furthermore, AhNPCs showed limited proliferative capacity that resulted in their depletion from culture by 5-6 passages, while the FbCs, which appear to be from a neurovascular origin, displayed a greater proliferative capacity and dominated the long-term cultures. This gradual change in cellular composition resulted in a progressive decline in neurogenic potential without the apparent loss of self renewal in our cultures. These results demonstrate that while AhNPCs and FbCs behave similarly under proliferative conditions, they are two different cell populations. This information is vital for the interpretation and reproducibility of AhNPC experiments and suggests an ideal time frame for conducting AhNPC-based experiments. PMID- 22675490 TI - A novel task for the investigation of action acquisition. AB - We present a behavioural task designed for the investigation of how novel instrumental actions are discovered and learnt. The task consists of free movement with a manipulandum, during which the full range of possible movements can be explored by the participant and recorded. A subset of these movements, the 'target', is set to trigger a reinforcing signal. The task is to discover what movements of the manipulandum evoke the reinforcement signal. Targets can be defined in spatial, temporal, or kinematic terms, can be a combination of these aspects, or can represent the concatenation of actions into a larger gesture. The task allows the study of how the specific elements of behaviour which cause the reinforcing signal are identified, refined and stored by the participant. The task provides a paradigm where the exploratory motive drives learning and as such we view it as in the tradition of Thorndike [1]. Most importantly it allows for repeated measures, since when a novel action is acquired the criterion for triggering reinforcement can be changed requiring a new action to be discovered. Here, we present data using both humans and rats as subjects, showing that our task is easily scalable in difficulty, adaptable across species, and produces a rich set of behavioural measures offering new and valuable insight into the action learning process. PMID- 22675491 TI - Genomic islands as a marker to differentiate between clinical and environmental Burkholderia pseudomallei. AB - Burkholderia pseudomallei, as a saprophytic bacterium that can cause a severe sepsis disease named melioidosis, has preserved several extra genes in its genome for survival. The sequenced genome of the organism showed high diversity contributed mainly from genomic islands (GIs). Comparative genome hybridization (CGH) of 3 clinical and 2 environmental isolates, using whole genome microarrays based on B. pseudomallei K96243 genes, revealed a difference in the presence of genomic islands between clinical and environmental isolates. The largest GI, GI8, of B. pseudomallei was observed as a 2 sub-GI named GIs8.1 and 8.2 with distinguishable %GC content and unequal presence in the genome. GIs8.1, 8.2 and 15 were found to be more common in clinical isolates. A new GI, GI16c, was detected on chromosome 2. Presences of GIs8.1, 8.2, 15 and 16c were evaluated in 70 environmental and 64 clinical isolates using PCR assays. A combination of GIs8.1 and 16c (positivity of either GI) was detected in 70% of clinical isolates and 11.4% of environmental isolates (P<0.001). Using BALB/c mice model, no significant difference of time to mortality was observed between K96243 isolate and three isolates without GIs under evaluation (P>0.05). Some virulence genes located in the absent GIs and the difference of GIs seems to contribute less to bacterial virulence. The PCR detection of 2 GIs could be used as a cost effective and rapid tool to detect potentially virulent isolates that were contaminated in soil. PMID- 22675492 TI - Genome-wide association study of circulating estradiol, testosterone, and sex hormone-binding globulin in postmenopausal women. AB - Genome-wide association studies (GWAS) have successfully identified common genetic variants that contribute to breast cancer risk. Discovering additional variants has become difficult, as power to detect variants of weaker effect with present sample sizes is limited. An alternative approach is to look for variants associated with quantitative traits that in turn affect disease risk. As exposure to high circulating estradiol and testosterone, and low sex hormone-binding globulin (SHBG) levels is implicated in breast cancer etiology, we conducted GWAS analyses of plasma estradiol, testosterone, and SHBG to identify new susceptibility alleles. Cancer Genetic Markers of Susceptibility (CGEMS) data from the Nurses' Health Study (NHS), and Sisters in Breast Cancer Screening data were used to carry out primary meta-analyses among ~1600 postmenopausal women who were not taking postmenopausal hormones at blood draw. We observed a genome-wide significant association between SHBG levels and rs727428 (joint beta = -0.126; joint P = 2.09 * 10(-16)), downstream of the SHBG gene. No genome-wide significant associations were observed with estradiol or testosterone levels. Among variants that were suggestively associated with estradiol (P<10(-5)), several were located at the CYP19A1 gene locus. Overall results were similar in secondary meta-analyses that included ~900 NHS current postmenopausal hormone users. No variant associated with estradiol, testosterone, or SHBG at P<10(-5) was associated with postmenopausal breast cancer risk among CGEMS participants. Our results suggest that the small magnitude of difference in hormone levels associated with common genetic variants is likely insufficient to detectably contribute to breast cancer risk. PMID- 22675493 TI - To be or not to be solitary: Phytophthora infestans' dilemma for optimizing its reproductive fitness in multiple infections. AB - The success of parasitic life lies in an optimal exploitation of the host to satisfy key functions directly involved in reproductive fitness. Resource availability generally decreases over time with host mortality, but also during multiple infections, where different strains of parasite share host resources. During multiple infections, the number of parasite strains and their genetic relatedness are known to influence their reproductive rates. Using infections of the potato plant Solanum tuberosum with the parasite Phytophthora infestans, we set up an experimental design to separate dose effects (double- vs. single-site infections) from genetic relatedness (different vs. identical genotypes) on the reproductive fitness of competing parasite genotypes. We showed the existence of two basic response patterns--increase or decrease in reproductive fitness in multiple infections- depending on the parasite genotype. In all cases, the intensity of the response of any genotype depended on the genotype of the competing strain. This diversity of responses to multiple infections is probably maintained by the fluctuating frequencies of multiple infections in nature, arising from variations in disease pressure over the course of an epidemic and between successive epidemics. It allows a rapid response of parasitic populations to changing environments, which are particularly intense in agricultural systems. PMID- 22675494 TI - Tuning the drug efflux activity of an ABC transporter in vivo by in vitro selected DARPin binders. AB - ABC transporters use the energy from binding and hydrolysis of ATP to import or extrude substrates across the membrane. Using ribosome display, we raised designed ankyrin repeat proteins (DARPins) against detergent solubilized LmrCD, a heterodimeric multidrug ABC exporter from Lactococcus lactis. Several target specific DARPin binders were identified that bind to at least three distinct, partially overlapping epitopes on LmrD in detergent solution as well as in native membranes. Remarkably, functional screening of the LmrCD-specific DARPin pools in L. lactis revealed three homologous DARPins which, when generated in LmrCD expressing cells, strongly activated LmrCD-mediated drug transport. As LmrCD expression in the cell membrane was unaltered upon the co-expression of activator DARPins, the activation is suggested to occur at the level of LmrCD activity. Consistent with this, purified activator DARPins were found to stimulate the ATPase activity of LmrCD in vitro when reconstituted in proteoliposomes. This study suggests that membrane transporters are tunable in vivo by in vitro selected binding proteins. Our approach could be of biopharmaceutical importance and might facilitate studies on molecular mechanisms of ABC transporters. PMID- 22675495 TI - Growth and demography of the solitary scleractinian coral Leptopsammia pruvoti along a sea surface temperature gradient in the Mediterranean Sea. AB - The demographic traits of the solitary azooxanthellate scleractinian Leptopsammia pruvoti were determined in six populations on a sea surface temperature (SST) gradient along the western Italian coasts. This is the first investigation of the growth and demography characteristics of an azooxanthellate scleractinian along a natural SST gradient. Growth rate was homogeneous across all populations, which spanned 7 degrees of latitude. Population age structures differed between populations, but none of the considered demographic parameters correlated with SST, indicating possible effects of local environmental conditions. Compared to another Mediterranean solitary scleractinian, Balanophyllia europaea, zooxanthellate and whose growth, demography and calcification have been studied in the same sites, L. pruvoti seems more tolerant to temperature increase. The higher tolerance of L. pruvoti, relative to B. europaea, may rely on the absence of symbionts, and thus the lack of an inhibition of host physiological processes by the heat-stressed zooxanthellae. However, the comparison between the two species must be taken cautiously, due to the likely temperature differences between the two sampling depths. Increasing research effort on determining the effects of temperature on the poorly studied azooxanthellate scleractinians may shed light on the possible species assemblage shifts that are likely to occur during the current century as a consequence of global climatic change. PMID- 22675496 TI - CXCR3 antagonism of SDF-1(5-67) restores trabecular function and prevents retinal neurodegeneration in a rat model of ocular hypertension. AB - Glaucoma, the most common cause of irreversible blindness, is a neuropathy commonly initiated by pathological ocular hypertension due to unknown mechanisms of trabecular meshwork degeneration. Current antiglaucoma therapy does not target the causal trabecular pathology, which may explain why treatment failure is often observed. Here we show that the chemokine CXCL12, its truncated form SDF-1(5-67), and the receptors CXCR4 and CXCR3 are expressed in human glaucomatous trabecular tissue and a human trabecular cell line. SDF-1(5-67) is produced under the control of matrix metallo-proteinases, TNF-alpha, and TGF-beta2, factors known to be involved in glaucoma. CXCL12 protects in vitro trabecular cells from apoptotic death via CXCR4 whereas SDF-1(5-67) induces apoptosis through CXCR3 and caspase activation. Ocular administration of SDF-1(5-67) in the rat increases intraocular pressure. In contrast, administration of a selective CXCR3 antagonist in a rat model of ocular hypertension decreases intraocular pressure, prevents retinal neurodegeneration, and preserves visual function. The protective effect of CXCR3 antagonism is related to restoration of the trabecular function. These data demonstrate that proteolytic cleavage of CXCL12 is involved in trabecular pathophysiology, and that local administration of a selective CXCR3 antagonist may be a beneficial therapeutic strategy for treating ocular hypertension and subsequent retinal degeneration. PMID- 22675497 TI - Phenotypic and transcriptomic response of auxotrophic Mycobacterium avium subsp. paratuberculosis leuD mutant under environmental stress. AB - Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of severe gastroenteritis in cattle. To gain a better understanding of MAP virulence, we investigated the role of leuD gene in MAP metabolism and stress response. For this, we have constructed an auxotrophic strain of MAP by deleting the leuD gene using allelic exchange. The wildtype and mutant strains were then compared for metabolic phenotypic changes using Biolog phenotype microarrays. The responses of both strains to physiologically relevant stress conditions were assessed using DNA microarrays. Transcriptomic data was then analyzed in the context of cellular metabolic pathways and gene networks. Our results showed that deletion of leuD gene has a global effect on both MAP phenotypic and transcriptome response. At the metabolic level, the mutant strain lost the ability to utilize most of the carbon, nitrogen, sulphur, phosphorus and nutrient supplements as energy source. At the transcriptome level, more than 100 genes were differentially expressed in each of the stress condition tested. Systems level network analysis revealed that the differentially expressed genes were distributed throughout the gene network, thus explaining the global impact of leuD deletion in metabolic phenotype. Further, we find that leuD deletion impacted metabolic pathways associated with fatty acids. We verified this by experimentally estimating the total fatty acid content of both mutant and wildtype. The mutant strain had 30% less fatty acid content when compared to wildtype, thus supporting the results from transcriptional and computational analyses. Our results therefore reveal the intricate connection between the metabolism and virulence in MAP. PMID- 22675498 TI - Deep sequencing of the oral microbiome reveals signatures of periodontal disease. AB - The oral microbiome, the complex ecosystem of microbes inhabiting the human mouth, harbors several thousands of bacterial types. The proliferation of pathogenic bacteria within the mouth gives rise to periodontitis, an inflammatory disease known to also constitute a risk factor for cardiovascular disease. While much is known about individual species associated with pathogenesis, the system level mechanisms underlying the transition from health to disease are still poorly understood. Through the sequencing of the 16S rRNA gene and of whole community DNA we provide a glimpse at the global genetic, metabolic, and ecological changes associated with periodontitis in 15 subgingival plaque samples, four from each of two periodontitis patients, and the remaining samples from three healthy individuals. We also demonstrate the power of whole-metagenome sequencing approaches in characterizing the genomes of key players in the oral microbiome, including an unculturable TM7 organism. We reveal the disease microbiome to be enriched in virulence factors, and adapted to a parasitic lifestyle that takes advantage of the disrupted host homeostasis. Furthermore, diseased samples share a common structure that was not found in completely healthy samples, suggesting that the disease state may occupy a narrow region within the space of possible configurations of the oral microbiome. Our pilot study demonstrates the power of high-throughput sequencing as a tool for understanding the role of the oral microbiome in periodontal disease. Despite a modest level of sequencing (~2 lanes Illumina 76 bp PE) and high human DNA contamination (up to ~90%) we were able to partially reconstruct several oral microbes and to preliminarily characterize some systems-level differences between the healthy and diseased oral microbiomes. PMID- 22675500 TI - The oncoprotein BCL11A binds to orphan nuclear receptor TLX and potentiates its transrepressive function. AB - Nuclear orphan receptor TLX (NR2E1) functions primarily as a transcriptional repressor and its pivotal role in brain development, glioblastoma, mental retardation and retinopathologies make it an attractive drug target. TLX is expressed in the neural stem cells (NSCs) of the subventricular zone and the hippocampus subgranular zone, regions with persistent neurogenesis in the adult brain, and functions as an essential regulator of NSCs maintenance and self renewal. Little is known about the TLX social network of interactors and only few TLX coregulators are described. To identify and characterize novel TLX-binders and possible coregulators, we performed yeast-two-hybrid (Y2H) screens of a human adult brain cDNA library using different TLX constructs as baits. Our screens identified multiple clones of Atrophin-1 (ATN1), a previously described TLX interactor. In addition, we identified an interaction with the oncoprotein and zinc finger transcription factor BCL11A (CTIP1/Evi9), a key player in the hematopoietic system and in major blood-related malignancies. This interaction was validated by expression and coimmunoprecipitation in human cells. BCL11A potentiated the transrepressive function of TLX in an in vitro reporter gene assay. Our work suggests that BCL11A is a novel TLX coregulator that might be involved in TLX-dependent gene regulation in the brain. PMID- 22675499 TI - Rabx-5 regulates RAB-5 early endosomal compartments and synaptic vesicles in C. elegans. AB - Early endosomal membrane compartments are required for the formation and recycling of synaptic vesicles, but how these compartments are regulated is incompletely understood. We performed a forward genetic screen in C. elegans for mutations that affect RAB-5 labeled early endosomal compartments in GABAergic motoneurons. Here we report the isolation and characterization of one mutation, rabx-5. The rabx-5 mutation leads to decreased intensity of YFP::RAB-5 in the cell soma but increased intensity in the synaptic and intersynaptic regions of the axon. This effect is due to the bias of the cycling state of RAB-5, and results from a change in the organization of the early endosomal compartment as well as the membrane binding state of RAB-5. Synaptic vesicle accumulation is altered in rabx-5 mutants, and synaptic transmission from cholinergic neurons is decreased. Early endosomal membrane compartments show disorganization with ageing and rabx-5 mutant animals age faster. These results suggest that rabx-5 regulation of RAB-5 compartments is important for maintaining proper synaptic function throughout the lifetime. PMID- 22675501 TI - Cycling of Etk and Etp phosphorylation states is involved in formation of group 4 capsule by Escherichia coli. AB - Capsules frequently play a key role in bacterial interactions with their environment. Escherichia coli capsules were categorized as groups 1 through 4, each produced by a distinct mechanism. Etk and Etp are members of protein families required for the production of group 1 and group 4 capsules. These members function as a protein tyrosine kinase and protein tyrosine phosphatase, respectively. We show that Etp dephosphorylates Etk in vivo, and mutations rendering Etk or Etp catalytically inactive result in loss of group 4 capsule production, supporting the notion that cyclic phosphorylation and dephosphorylation of Etk is required for capsule formation. Notably, Etp also becomes tyrosine phosphorylated in vivo and catalyzes rapid auto dephosphorylation. Further analysis identified Tyr121 as the phosphorylated residue of Etp. Etp containing Phe, Glu or Ala in place of Tyr121 retained phosphatase activity and catalyzed dephosphorylation of Etp and Etk. Although EtpY121E and EtpY121A still supported capsule formation, EtpY121F failed to do so. These results suggest that cycles of phosphorylation and dephosphorylation of Etp, as well as Etk, are involved in the formation of group 4 capsule, providing an additional regulatory layer to the complex control of capsule production. PMID- 22675502 TI - Identifying live bird markets with the potential to act as reservoirs of avian influenza A (H5N1) virus: a survey in northern Viet Nam and Cambodia. AB - Wet markets are common in many parts of the world and may promote the emergence, spread and maintenance of livestock pathogens, including zoonoses. A survey was conducted in order to assess the potential of Vietnamese and Cambodian live bird markets (LBMs) to sustain circulation of highly pathogenic avian influenza virus subtype H5N1 (HPAIV H5N1). Thirty Vietnamese and 8 Cambodian LBMs were visited, and structured interviews were conducted with the market managers and 561 Vietnamese and 84 Cambodian traders. Multivariate and cluster analysis were used to construct a typology of traders based on their poultry management practices. As a result of those practices and large poultry surplus (unsold poultry reoffered for sale the following day), some poultry traders were shown to promote conditions favorable for perpetuating HPAIV H5N1 in LBMs. More than 80% of these traders operated in LBMs located in the most densely populated areas, Ha Noi and Phnom Penh. The profiles of sellers operating at a given LBM could be reliably predicted using basic information about the location and type of market. Consequently, LBMs with the largest combination of risk factors for becoming virus reservoirs could be easily identified, potentially allowing control strategies to be appropriately targeted. These findings are of particular relevance to resource-scarce settings with extensively developed LBM systems, commonly found in South-East Asia. PMID- 22675503 TI - MEG can map short and long-term changes in brain activity following deep brain stimulation for chronic pain. AB - Deep brain stimulation (DBS) has been shown to be clinically effective for some forms of treatment-resistant chronic pain, but the precise mechanisms of action are not well understood. Here, we present an analysis of magnetoencephalography (MEG) data from a patient with whole-body chronic pain, in order to investigate changes in neural activity induced by DBS for pain relief over both short- and long-term. This patient is one of the few cases treated using DBS of the anterior cingulate cortex (ACC). We demonstrate that a novel method, null-beamforming, can be used to localise accurately brain activity despite the artefacts caused by the presence of DBS electrodes and stimulus pulses. The accuracy of our source localisation was verified by correlating the predicted DBS electrode positions with their actual positions. Using this beamforming method, we examined changes in whole-brain activity comparing pain relief achieved with deep brain stimulation (DBS ON) and compared with pain experienced with no stimulation (DBS OFF). We found significant changes in activity in pain-related regions including the pre-supplementary motor area, brainstem (periaqueductal gray) and dissociable parts of caudal and rostral ACC. In particular, when the patient reported experiencing pain, there was increased activity in different regions of ACC compared to when he experienced pain relief. We were also able to demonstrate long-term functional brain changes as a result of continuous DBS over one year, leading to specific changes in the activity in dissociable regions of caudal and rostral ACC. These results broaden our understanding of the underlying mechanisms of DBS in the human brain. PMID- 22675504 TI - In vivo human apolipoprotein E isoform fractional turnover rates in the CNS. AB - Apolipoprotein E (ApoE) is the strongest genetic risk factor for Alzheimer's disease and has been implicated in the risk for other neurological disorders. The three common ApoE isoforms (ApoE2, E3, and E4) each differ by a single amino acid, with ApoE4 increasing and ApoE2 decreasing the risk of Alzheimer's disease (AD). Both the isoform and amount of ApoE in the brain modulate AD pathology by altering the extent of amyloid beta (Abeta) peptide deposition. Therefore, quantifying ApoE isoform production and clearance rates may advance our understanding of the role of ApoE in health and disease. To measure the kinetics of ApoE in the central nervous system (CNS), we applied in vivo stable isotope labeling to quantify the fractional turnover rates of ApoE isoforms in 18 cognitively-normal adults and in ApoE3 and ApoE4 targeted-replacement mice. No isoform-specific differences in CNS ApoE3 and ApoE4 turnover rates were observed when measured in human CSF or mouse brain. However, CNS and peripheral ApoE isoform turnover rates differed substantially, which is consistent with previous reports and suggests that the pathways responsible for ApoE metabolism are different in the CNS and the periphery. We also demonstrate a slower turnover rate for CSF ApoE than that for amyloid beta, another molecule critically important in AD pathogenesis. PMID- 22675505 TI - Estradiol attenuates ischemia-induced death of hippocampal neurons and enhances synaptic transmission in aged, long-term hormone-deprived female rats. AB - BACKGROUND: Transient global forebrain ischemia causes selective, delayed death of hippocampal CA1 pyramidal neurons, and the ovarian hormone 17beta-estradiol (E2) reduces neuronal loss in young and middle-aged females. The neuroprotective efficacy of E2 after a prolonged period of hormone deprivation is controversial, and few studies examine this issue in aged animals given E2 treatment after induction of ischemia. METHODOLOGY/PRINCIPAL FINDINGS: The present study investigated the neuroprotective effects of E2 administered immediately after global ischemia in aged female rats (15-18 months) after 6 months of hormone deprivation. We also used electrophysiological methods to assess whether CA1 synapses in the aging hippocampus remain responsive to E2 after prolonged hormone withdrawal. Animals were ovariohysterectomized and underwent 10 min global ischemia 6 months later. A single dose of E2 (2.25 ug) infused intraventricularly after reperfusion significantly increased cell survival, with 45% of CA1 neurons surviving vs 15% in controls. Ischemia also induced moderate loss of CA3/CA4 pyramidal cells. Bath application of 1 nM E2 onto brain slices derived from non ischemic aged females after 6 months of hormone withdrawal significantly enhanced excitatory transmission at CA1 synapses evoked by Schaffer collateral stimulation, and normal long-term potentiation (LTP) was induced. The magnitude of LTP and of E2 enhancement of field excitatory postsynaptic potentials was indistinguishable from that recorded in slices from young rats. CONCLUSIONS/SIGNIFICANCE: The data demonstrate that 1) acute post-ischemic infusion of E2 into the brain ventricles is neuroprotective in aged rats after 6 months of hormone deprivation; and 2) E2 enhances synaptic transmission in CA1 pyramidal neurons of aged long-term hormone deprived females. These findings provide evidence that the aging hippocampus remains responsive to E2 administered either in vivo or in vitro even after prolonged periods of hormone withdrawal. PMID- 22675506 TI - Topical polyethylene glycol as a novel chemopreventive agent for oral cancer via targeting of epidermal growth factor response. AB - Head and neck squamous cell carcinoma (HNSCC) is a major cause of morbidity and mortality underscoring the need for safe and effective chemopreventive strategies. Targeting epidermal growth factor receptor (EGFR) is attractive in that it is an early critical event in HNSCC pathogenesis. However, current agents lack efficacy or have unacceptable toxicity. Several groups have demonstrated that the over-the-counter medication, polyethylene glycol (PEG) has remarkable chemopreventive efficacy against colon carcinogenesis. Importantly, we reported that this effect is mediated through EGFR internalization/degradation. In the current study, we investigated the chemopreventive efficacy of this agent against HNSCC, using both the well validated animal model 4-NQO (4-nitroquinoline 1 oxide) rat model and cell culture with the human HNSCC cell line SCC-25. We demonstrated that daily topical application of 10% PEG-8000 in the oral cavity (tongue and cavity wall) post 4NQO initiation resulted in a significant reduction in tumor burden (both, tumor size and tumors/tumor bearing rat) without any evidence of toxicity. Immunohistochemical studies depicted decreased proliferation (number of Ki67-positive cells) and reduced expression of EGFR and its downstream effectors cyclin D1 in the tongue mucosa of 4NQO-rats treated with PEG. We showed that EGFR was also markedly downregulated in SCC-25 cells by PEG 8000 with a concomitant induction of G1-S phase cell-cycle arrest, which was potentially mediated through upregulated p21(cip1/waf1). In conclusion, we demonstrate, for the first time, that PEG has promising efficacy and safety as a chemopreventive efficacy against oral carcinogenesis. PMID- 22675507 TI - Low pathogenic avian influenza isolates from wild birds replicate and transmit via contact in ferrets without prior adaptation. AB - Direct transmission of avian influenza viruses to mammals has become an increasingly investigated topic during the past decade; however, isolates that have been primarily investigated are typically ones originating from human or poultry outbreaks. Currently there is minimal comparative information on the behavior of the innumerable viruses that exist in the natural wild bird host. We have previously demonstrated the capacity of numerous North American avian influenza viruses isolated from wild birds to infect and induce lesions in the respiratory tract of mice. In this study, two isolates from shorebirds that were previously examined in mice (H1N9 and H6N1 subtypes) are further examined through experimental inoculations in the ferret with analysis of viral shedding, histopathology, and antigen localization via immunohistochemistry to elucidate pathogenicity and transmission of these viruses. Using sequence analysis and glycan binding analysis, we show that these avian viruses have the typical avian influenza binding pattern, with affinity for cell glycoproteins/glycolipids having terminal sialic acid (SA) residues with alpha 2,3 linkage [Neu5Ac(alpha2,3)Gal]. Despite the lack of alpha2,6 linked SA binding, these AIVs productively infected both the upper and lower respiratory tract of ferrets, resulting in nasal viral shedding and pulmonary lesions with minimal morbidity. Moreover, we show that one of the viruses is able to transmit to ferrets via direct contact, despite its binding affinity for alpha 2,3 linked SA residues. These results demonstrate that avian influenza viruses, which are endemic in aquatic birds, can potentially infect humans and other mammals without adaptation. Finally this work highlights the need for additional study of the wild bird subset of influenza viruses in regard to surveillance, transmission, and potential for reassortment, as they have zoonotic potential. PMID- 22675508 TI - Quality of longer term mental health facilities in Europe: validation of the quality indicator for rehabilitative care against service users' views. AB - BACKGROUND: The Quality Indicator for Rehabilitative Care (QuIRC) is a staff rated, international toolkit that assesses care in longer term hospital and community based mental health facilities. The QuIRC was developed from review of the international literature, an international Delphi exercise with over 400 service users, practitioners, carers and advocates from ten European countries at different stages of deinstitutionalisation, and review of the care standards in these countries. It can be completed in under an hour by the facility manager and has robust content validity, acceptability and inter-rater reliability. In this study, we investigated the internal validity of the QuIRC. Our aim was to identify the QuIRC domains of care that independently predicted better service user experiences of care. METHOD: At least 20 units providing longer term care for adults with severe mental illness were recruited in each of ten European countries. Service users completed standardised measures of their experiences of care, quality of life, autonomy and the unit's therapeutic milieu. Unit managers completed the QuIRC. Multilevel modelling allowed analysis of associations between service user ratings as dependent variables with unit QuIRC domain ratings as independent variables. RESULTS: 1750/2495 (70%) users and the managers of 213 units from across ten European countries participated. QuIRC ratings were positively associated with service users' autonomy and experiences of care. Associations between QuIRC ratings and service users' ratings of their quality of life and the unit's therapeutic milieu were explained by service user characteristics (age, diagnosis and functioning). A hypothetical 10% increase in QuIRC rating resulted in a clinically meaningful improvement in autonomy. CONCLUSIONS: Ratings of the quality of longer term mental health facilities made by service managers were positively associated with service users' autonomy and experiences of care. Interventions that improve quality of care in these settings may promote service users' autonomy. PMID- 22675509 TI - Demethylation of the coding region triggers the activation of the human testis specific PDHA2 gene in somatic tissues. AB - Human PDHA2 is a testis-specific gene that codes for the E(1)alpha subunit of Pyruvate Dehydrogenase Complex (PDC), a crucial enzyme system in cell energy metabolism. Since activation of the PDHA2 gene in somatic cells could be a new therapeutic approach for PDC deficiency, we aimed to identify the regulatory mechanisms underlying the human PDHA2 gene expression. Functional deletion studies revealed that the -122 to -6 promoter region is indispensable for basal expression of this TATA-less promoter, and suggested a role of an epigenetic program in the control of PDHA2 gene expression. Indeed, treatment of SH-SY5Y cells with the hypomethylating agent 5-Aza-2'-deoxycytidine (DAC) promoted the reactivation of the PDHA2 gene, by inducing the recruitment of the RNA polymerase II to the proximal promoter region and the consequent increase in PDHA2 mRNA levels. Bisulfite sequencing analysis revealed that DAC treatment induced a significant demethylation of the CpG island II (nucleotides +197 to +460) in PDHA2 coding region, while the promoter region remained highly methylated. Taken together with our previous results that show an in vivo correlation between PDHA2 expression and the demethylation of the CpG island II in testis germ cells, the present results show that internal methylation of the PDHA2 gene plays a part in its repression in somatic cells. In conclusion, our data support the novel finding that methylation of the PDHA2 coding region can inhibit gene transcription. This represents a key mechanism for absence of PDHA2 expression in somatic cells and a target for PDC therapy. PMID- 22675510 TI - Selective impact of HIV disease progression on the innate immune system in the human female reproductive tract. AB - BACKGROUND: We have previously demonstrated intrinsic anti-HIV activity in cervicovaginal lavage (CVL) from HIV-infected women with high CD4 counts and not on antiretroviral therapy. However, the impact of HIV disease progression on CVL innate immune responses has not been delineated. METHODS: CVL from 57 HIV infected women not on antiretroviral therapy were collected by washing the cervicovaginal area with 10 ml of sterile normal saline. We characterized subject HIV disease progression by CD4 count strata: >500 cells/ul, 200-500 cells/ul, or <200 cells/ul of blood. To assess CVL anti-HIV activity, we incubated TZM-bl cells with HIV plus or minus CVL. Antimicrobials, cytokines, chemokines and anti gp160 HIV IgG antibodies were measured by ELISA and Luminex. RESULTS: CVL exhibited broad anti-HIV activity against multiple laboratory-adapted and transmitted/founder (T/F) viruses, with anti-HIV activity ranging from 0 to 100% showing wide variation between viral strains. Although there was broad CVL inhibition of most both laboratory-adapted and T/F virus strains, there was practically no inhibition of T/F strain RHPA.c, which was isolated from a woman newly infected via heterosexual intercourse. HIV disease progression, measured by declining CD4 T cell counts, resulted in a selective reduction in intrinsic anti HIV activity in CVL that paralleled CVL decreases in human beta-defensin 2 and increases in Elafin and secretory leukocyte protease inhibitor. HIV disease progress predicted decreased CVL anti-HIV activity against both laboratory adapted and T/F strains of HIV. Anti-HIV activity exhibited close associations with CVL levels of fourteen cytokines and chemokines. CONCLUSIONS: Amid a multifaceted immune defense against HIV-1 and other sexually transmitted pathogens, HIV disease progression is associated with selective disturbances in both CVL anti-HIV activity and specific innate immune defenses in the human female reproductive tract (FRT). Overall, these studies indicate that innate immune protection in the FRT is compromised as women progress to AIDS. PMID- 22675511 TI - Modulation of mouse coagulation gene transcription following acute in vivo delivery of synthetic small interfering RNAs targeting HNF4alpha and C/EBPalpha. AB - Hepatocyte nuclear factor 4alpha (HNF4alpha) and CCAAT/enhancer-binding protein alpha (C/EBPalpha) are important for the transcriptional control of coagulation factors. To determine in vivo the direct role of HNF4alpha and C/EBPalpha in control of genes encoding coagulation factors, a synthetic small interfering (si)RNA approach was used that enabled strong reduction of mouse hepatic HNF4alpha and C/EBPalpha under conditions that minimized target-related secondary effects. For both HNF4alpha and C/EBPalpha, intravenous injection of specific synthetic siRNAs (siHNF4alpha and siC/EBPalpha) resulted in more than 75% reduction in their liver transcript and protein levels 2 days post-injection. For siHNF4alpha, this coincided with marked and significantly reduced transcript levels of the coagulation genes Hrg, Proz, Serpina5, F11, F12, F13b, Serpinf2, F5, and F9 (in order of magnitude of effect) as compared to levels in control siRNA injected animals. Significant decreases in HNF4alpha target gene mRNA levels were also observed at 5 days post-siRNA injection, despite a limited level of HNF4alpha knockdown at this time point. Compared to HNF4alpha, C/EBPalpha knockdown had a modest impact on genes encoding coagulation factors. A strong reduction in C/EBPalpha transcript and protein levels resulted in significantly affected transcript levels of the control genes Pck1 and Fasn and a modest downregulation for coagulation genes Fba, Fbg and F5. F5 and F11 were the sole coagulation genes that were significantly affected upon prolonged (5 day) C/EBPalpha knockdown. We conclude that in the mouse, HNF4alpha has a direct and essential regulatory role for multiple hepatic coagulation genes, while a role for C/EBPalpha is more restricted. In addition, this study demonstrates that synthetic siRNA provides a simple and fast means for determining liver transcription factor involvement in vivo. PMID- 22675512 TI - Coordinating environmental genomics and geochemistry reveals metabolic transitions in a hot spring ecosystem. AB - We have constructed a conceptual model of biogeochemical cycles and metabolic and microbial community shifts within a hot spring ecosystem via coordinated analysis of the "Bison Pool" (BP) Environmental Genome and a complementary contextual geochemical dataset of ~75 geochemical parameters. 2,321 16S rRNA clones and 470 megabases of environmental sequence data were produced from biofilms at five sites along the outflow of BP, an alkaline hot spring in Sentinel Meadow (Lower Geyser Basin) of Yellowstone National Park. This channel acts as a >22 m gradient of decreasing temperature, increasing dissolved oxygen, and changing availability of biologically important chemical species, such as those containing nitrogen and sulfur. Microbial life at BP transitions from a 92 degrees C chemotrophic streamer biofilm community in the BP source pool to a 56 degrees C phototrophic mat community. We improved automated annotation of the BP environmental genomes using BLAST-based Markov clustering. We have also assigned environmental genome sequences to individual microbial community members by complementing traditional homology-based assignment with nucleotide word-usage algorithms, allowing more than 70% of all reads to be assigned to source organisms. This assignment yields high genome coverage in dominant community members, facilitating reconstruction of nearly complete metabolic profiles and in-depth analysis of the relation between geochemical and metabolic changes along the outflow. We show that changes in environmental conditions and energy availability are associated with dramatic shifts in microbial communities and metabolic function. We have also identified an organism constituting a novel phylum in a metabolic "transition" community, located physically between the chemotroph- and phototroph-dominated sites. The complementary analysis of biogeochemical and environmental genomic data from BP has allowed us to build ecosystem-based conceptual models for this hot spring, reconstructing whole metabolic networks in order to illuminate community roles in shaping and responding to geochemical variability. PMID- 22675513 TI - Real-time self-regulation of emotion networks in patients with depression. AB - Many patients show no or incomplete responses to current pharmacological or psychological therapies for depression. Here we explored the feasibility of a new brain self-regulation technique that integrates psychological and neurobiological approaches through neurofeedback with functional magnetic resonance imaging (fMRI). In a proof-of-concept study, eight patients with depression learned to upregulate brain areas involved in the generation of positive emotions (such as the ventrolateral prefrontal cortex (VLPFC) and insula) during four neurofeedback sessions. Their clinical symptoms, as assessed with the 17-item Hamilton Rating Scale for Depression (HDRS), improved significantly. A control group that underwent a training procedure with the same cognitive strategies but without neurofeedback did not improve clinically. Randomised blinded clinical trials are now needed to exclude possible placebo effects and to determine whether fMRI based neurofeedback might become a useful adjunct to current therapies for depression. PMID- 22675514 TI - A new mouse model for mania shares genetic correlates with human bipolar disorder. AB - Bipolar disorder (BPD) is a debilitating heritable psychiatric disorder. Contemporary rodent models for the manic pole of BPD have primarily utilized either single locus transgenics or treatment with psychostimulants. Our lab recently characterized a mouse strain termed Madison (MSN) that naturally displays a manic phenotype, exhibiting elevated locomotor activity, increased sexual behavior, and higher forced swimming relative to control strains. Lithium chloride and olanzapine treatments attenuate this phenotype. In this study, we replicated our locomotor activity experiment, showing that MSN mice display generationally-stable mania relative to their outbred ancestral strain, hsd:ICR (ICR). We then performed a gene expression microarray experiment to compare hippocampus of MSN and ICR mice. We found dysregulation of multiple transcripts whose human orthologs are associated with BPD and other psychiatric disorders including schizophrenia and ADHD, including: Epor, Smarca4, Cmklr1, Cat, Tac1, Npsr1, Fhit, and P2rx7. RT-qPCR confirmed dysregulation for all of seven transcripts tested. Using a novel genome enrichment algorithm, we found enrichment in genome regions homologous to human loci implicated in BPD in replicated linkage studies including homologs of human cytobands 1p36, 3p14, 3q29, 6p21-22, 12q24, 16q24, and 17q25. Using a functional network analysis, we found dysregulation of a gene system related to chromatin packaging, a result convergent with recent human findings on BPD. Our findings suggest that MSN mice represent a polygenic model for the manic pole of BPD showing much of the genetic systems complexity of the corresponding human disorder. Further, the high degree of convergence between our findings and the human literature on BPD brings up novel questions about evolution by analogy in mammalian genomes. PMID- 22675516 TI - mPSQed: a software for the design of multiplex pyrosequencing assays. AB - Molecular-based diagnostic assays are the gold standard for infectious diseases today, since they allow a rapid and sensitive identification and typing of various pathogens. While PCR can be designed to be specific for a certain pathogen, a subsequent sequence analysis is frequently required for confirmation or typing. The design of appropriate PCR-based assays is a complex task, especially when conserved discriminating polymorphisms are rare or if the number of types which need to be differentiated is high. One extremely useful but underused method for this purpose is the multiplex pyrosequencing technique. Unfortunately there is no software available to aid researchers in designing multiplex pyrosequencing assays. Here, we present mPSQed (Multiplex PyroSeQuencing EDitor), a program targeted at closing this gap. We also present the design of an exemplarily theoretical assay for the differentiation of human adenovirus types A-F using two pyrosequencing primers on two distinct PCR products, designed quickly and easily using our software. PMID- 22675515 TI - Palytoxin and an Ostreopsis toxin extract increase the levels of mRNAs encoding inflammation-related proteins in human macrophages via p38 MAPK and NF-kappaB. AB - BACKGROUND: Palytoxin and, likely, its analogues produced by the dinoflagellate genus Ostreopsis, represent a class of non-proteinaceous compounds displaying high toxicity in animals. Owing to the wide distribution and the poisonous effects of these toxins in humans, their chemistry and mechanism of action have generated a growing scientific interest. Depending on the exposure route, palytoxin and its Ostreopsis analogues may cause several adverse effects on human health, including acute inflammatory reactions which seem more typical of cutaneous and inhalation contact. These observations have led us to hypothesize that these toxins may activate pro-inflammatory signalling cascades. METHODOLOGY AND PRINCIPAL FINDINGS: Here we demonstrate that palytoxin and a semi-purified Ostreopsis cf. ovata toxin extract obtained from a cultured strain isolated in the NW Adriatic Sea and containing a putative palytoxin and all the ovatoxins so far known--including the recently identified ovatoxin-f--significantly increase the levels of mRNAs encoding inflammation-related proteins in immune cells, i.e. monocyte-derived human macrophages, as assessed by Real-Time PCR analysis. Western immunoblot and electrophoretic mobility shift assays revealed that nuclear transcription factor -kappaB (NF-kappaB) is activated in cells exposed to toxins in coincidence with reduced levels of the inhibitory protein IkappaB alpha. Moreover, Mitogen-Activated Protein Kinases (MAPK) were phosphorylated in response to palytoxin, as also reported by others, and to the Ostreopsis toxin extract, as shown here for the first time. By using specific chemical inhibitors, the involvement of NF-kappaB and p38 MAPK in the toxin-induced transcription and accumulation of Cycloxigenase-2, Tumor Necrosis Factor-alpha, and Interleukin-8 transcripts has been demonstrated. CONCLUSIONS AND SIGNIFICANCE: The identification of specific molecular targets of palytoxin and its Ostreopsis analogues, besides contributing to expand the still limited knowledge of the intracellular signalling cascades affected by these toxins, may have important implications in setting up focused pharmacological interventions, replacing currently used symptomatic treatments. PMID- 22675517 TI - Lateral orbitofrontal cortex involvement in initial negative aesthetic impression formation. AB - It is well established that aesthetic appreciation is related with activity in several different brain regions. The identification of the neural correlates of beauty or liking ratings has been the focus of most prior studies. Not much attention has been directed towards the fact that humans are surrounded by objects that lead them to experience aesthetic indifference or leave them with a negative aesthetic impression. Here we explore the neural substrate of such experiences. Given the neuroimaging techniques that have been used, little is known about the temporal features of such brain activity. By means of magnetoencephalography we registered the moment at which brain activity differed while participants viewed images they considered to be beautiful or not. Results show that the first differential activity appears between 300 and 400 ms after stimulus onset. During this period activity in right lateral orbitofrontal cortex (lOFC) was greater while participants rated visual stimuli as not beautiful than when they rated them as beautiful. We argue that this activity is associated with an initial negative aesthetic impression formation, driven by the relative hedonic value of stimuli regarded as not beautiful. Additionally, our results contribute to the understanding of the nature of the functional roles of the lOFC. PMID- 22675518 TI - New mutations in chronic lymphocytic leukemia identified by target enrichment and deep sequencing. AB - Chronic lymphocytic leukemia (CLL) is a heterogeneous disease without a well defined genetic alteration responsible for the onset of the disease. Several lines of evidence coincide in identifying stimulatory and growth signals delivered by B-cell receptor (BCR), and co-receptors together with NFkB pathway, as being the driving force in B-cell survival in CLL. However, the molecular mechanism responsible for this activation has not been identified. Based on the hypothesis that BCR activation may depend on somatic mutations of the BCR and related pathways we have performed a complete mutational screening of 301 selected genes associated with BCR signaling and related pathways using massive parallel sequencing technology in 10 CLL cases. Four mutated genes in coding regions (KRAS, SMARCA2, NFKBIE and PRKD3) have been confirmed by capillary sequencing. In conclusion, this study identifies new genes mutated in CLL, all of them in cases with progressive disease, and demonstrates that next-generation sequencing technologies applied to selected genes or pathways of interest are powerful tools for identifying novel mutational changes. PMID- 22675519 TI - Response of the diatom Phaeodactylum tricornutum to photooxidative stress resulting from high light exposure. AB - The response of microalgae to photooxidative stress resulting from high light exposure is a well-studied phenomenon. However, direct analyses of photosystem II (PSII) D1 protein (the main target of photoinhibition) in diatoms are scarce. In this study, the response of the diatom model species Phaeodactylum tricornutum to short-term exposure to high light was examined and the levels of D1 protein determined immunochemically. Low light (LL) acclimated cells (40 umol photons m( 2) s(-1)) subjected to high light (HL, 1,250 umol photons m(-2) s(-1)) showed rapid induction of non-photochemical quenching (NPQ) and ca. 20-fold increase in diatoxanthin (DT) concentration. This resulted from the conversion of diadinoxanthin (DD) to DT through the activation of the DD-cycle. D1 protein levels under LL decreased about 30% after 1 h of the addition of lincomycin (LINC), a chloroplast protein synthesis inhibitor, showing significant D1 degradation and repair under low irradiance. Exposure to HL lead to a 3.2-fold increase in D1 degradation rate, whereas average D1 repair rate was 1.3-x higher under HL than LL, leading to decreased levels of D1 protein under HL. There were significant effects of both HL and LINC on P. tricornutum maximum quantum yield of PSII (F(v)/F(m)), showing a reduction of active PSII reaction centres. Partial recovery of F(v)/F(m) in the dark demonstrates the photosynthetic resilience of this diatom to changes in the light regime. P. tricornutum showed high allocation of total protein to D1 and an active D1-repair cycle to limit photoinhibition. PMID- 22675520 TI - Indocyanine green (ICG) lymphography is superior to lymphoscintigraphy for diagnostic imaging of early lymphedema of the upper limbs. AB - BACKGROUND: Secondary lymphedema causes swelling in limbs due to lymph retention following lymph node dissection in cancer therapy. Initiation of treatment soon after appearance of edema is very important, but there is no method for early diagnosis of lymphedema. In this study, we compared the utility of four diagnostic imaging methods: magnetic resonance imaging (MRI), computed tomography (CT), lymphoscintigraphy, and Indocyanine Green (ICG) lymphography. PATIENTS AND METHODS: Between April 2010 and November 2011, we examined 21 female patients (42 arms) with unilateral mild upper limb lymphedema using the four methods. The mean age of the patients was 60.4 years old (35-81 years old). Biopsies of skin and collecting lymphatic vessels were performed in 7 patients who underwent lymphaticovenous anastomosis. RESULTS: The specificity was 1 for all four methods. The sensitivity was 1 in ICG lymphography and MRI, 0.62 in lymphoscintigraphy, and 0.33 in CT. These results show that MRI and ICG lymphography are superior to lymphoscintigraphy or CT for diagnosis of lymphedema. In some cases, biopsy findings suggested abnormalities in skin and lymphatic vessels for which lymphoscintigraphy showed no abnormal findings. ICG lymphography showed a dermal backflow pattern in these cases. CONCLUSIONS: Our findings suggest the importance of dual diagnosis by examination of the lymphatic system using ICG lymphography and evaluation of edema in subcutaneous fat tissue using MRI. PMID- 22675521 TI - Key physiological parameters dictate triggering of activity-dependent bulk endocytosis in hippocampal synapses. AB - To maintain neurotransmission in central neurons, several mechanisms are employed to retrieve synaptically exocytosed membrane. The two major modes of synaptic vesicle (SV) retrieval are clathrin-mediated endocytosis and activity-dependent bulk endocytosis (ADBE). ADBE is the dominant SV retrieval mode during intense stimulation, however the precise physiological conditions that trigger this mode are not resolved. To determine these parameters we manipulated rat hippocampal neurons using a wide spectrum of stimuli by varying both the pattern and duration of stimulation. Using live-cell fluorescence imaging and electron microscopy approaches, we established that stimulation frequency, rather than the stimulation load, was critical in the triggering of ADBE. Thus two hundred action potentials, when delivered at high frequency, were sufficient to induce near maximal bulk formation. Furthermore we observed a strong correlation between SV pool size and ability to perform ADBE. We also identified that inhibitory nerve terminals were more likely to utilize ADBE and had a larger SV recycling pool. Thus ADBE in hippocampal synaptic terminals is tightly coupled to stimulation frequency and is more likely to occur in terminals with large SV pools. These results implicate ADBE as a key modulator of both hippocampal neurotransmission and plasticity. PMID- 22675522 TI - Early dengue virus protein synthesis induces extensive rearrangement of the endoplasmic reticulum independent of the UPR and SREBP-2 pathway. AB - The rearrangement of intracellular membranes has been long reported to be a common feature in diseased cells. In this study, we used dengue virus (DENV) to study the role of the unfolded protein response (UPR) and sterol-regulatory element-binding-protein-2 (SREBP-2) pathway in the rearrangement and expansion of the endoplasmic reticulum (ER) early after infection. Using laser scanning confocal and differential interference contrast microscopy, we demonstrate that rearrangement and expansion of the ER occurs early after DENV-2 infection. Through the use of mouse embryonic fibroblast cells deficient in XBP1 and ATF6, we show that ER rearrangement early after DENV infection is independent of the UPR. We then demonstrate that enlargement of the ER is independent of the SREBP-2 activation and upregulation of 3-hydroxy-3-methylglutaryl-Coenzyme-A reductase, the rate-limiting enzyme in the cholesterol biosynthesis pathway. We further show that this ER rearrangement is not inhibited by the treatment of DENV-infected cells with the cholesterol-inhibiting drug lovastatin. Using the transcription inhibitor actinomycin D and the translation elongation inhibitor cycloheximide, we show that de novo viral protein synthesis but not host transcription is necessary for expansion and rearrangement of the ER. Lastly, we demonstrate that viral infection induces the reabsorption of lipid droplets into the ER. Together, these results demonstrate that modulation of intracellular membrane architecture of the cell early after DENV-2 infection is driven by viral protein expression and does not require the induction of the UPR and SREBP-2 pathways. This work paves the way for further study of virally-induced membrane rearrangements and formation of cubic membranes. PMID- 22675523 TI - Incorporation of DPP6a and DPP6K variants in ternary Kv4 channel complex reconstitutes properties of A-type K current in rat cerebellar granule cells. AB - Dipeptidyl peptidase-like protein 6 (DPP6) proteins co-assemble with Kv4 channel alpha-subunits and Kv channel-interacting proteins (KChIPs) to form channel protein complexes underlying neuronal somatodendritic A-type potassium current (I(SA)). DPP6 proteins are expressed as N-terminal variants (DPP6a, DPP6K, DPP6S, DPP6L) that result from alternative mRNA initiation and exhibit overlapping expression patterns. Here, we study the role DPP6 variants play in shaping the functional properties of I(SA) found in cerebellar granule (CG) cells using quantitative RT-PCR and voltage-clamp recordings of whole-cell currents from reconstituted channel complexes and native I(SA) channels. Differential expression of DPP6 variants was detected in rat CG cells, with DPP6K (41 +/- 3%)>DPP6a (33 +/- 3%)>>DPP6S (18 +/- 2%)>DPP6L (8 +/- 3%). To better understand how DPP6 variants shape native neuronal I(SA), we focused on studying interactions between the two dominant variants, DPP6K and DPP6a. Although previous studies did not identify unique functional effects of DPP6K, we find that the unique N-terminus of DPP6K modulates the effects of KChIP proteins, slowing recovery and producing a negative shift in the steady-state inactivation curve. By contrast, DPP6a uses its distinct N-terminus to directly confer rapid N type inactivation independently of KChIP3a. When DPP6a and DPP6K are co-expressed in ratios similar to those found in CG cells, their distinct effects compete in modulating channel function. The more rapid inactivation from DPP6a dominates during strong depolarization; however, DPP6K produces a negative shift in the steady-state inactivation curve and introduces a slow phase of recovery from inactivation. A direct comparison to the native CG cell I(SA) shows that these mixed effects are present in the native channels. Our results support the hypothesis that the precise expression and co-assembly of different auxiliary subunit variants are important factors in shaping the I(SA) functional properties in specific neuronal populations. PMID- 22675524 TI - Reduced myelin basic protein and actin-related gene expression in visual cortex in schizophrenia. AB - Most brain gene expression studies of schizophrenia have been conducted in the frontal cortex or hippocampus. The extent to which alterations occur in other cortical regions is not well established. We investigated primary visual cortex (Brodmann area 17) from the Stanley Neuropathology Consortium collection of tissue from 60 subjects with schizophrenia, bipolar disorder, major depression, or controls. We first carried out a preliminary array screen of pooled RNA, and then used RT-PCR to quantify five mRNAs which the array identified as differentially expressed in schizophrenia (myelin basic protein [MBP], myelin oligodendrocyte glycoprotein [MOG], beta-actin [ACTB], thymosin beta-10 [TB10], and superior cervical ganglion-10 [SCG10]). Reduced mRNA levels were confirmed by RT-PCR for MBP, ACTB and TB10. The MBP reduction was limited to transcripts containing exon 2. ACTB and TB10 mRNAs were also decreased in bipolar disorder. None of the transcripts were altered in subjects with major depression. Reduced MBP mRNA in schizophrenia replicates findings in other brain regions and is consistent with oligodendrocyte involvement in the disorder. The decreases in expression of ACTB, and the actin-binding protein gene TB10, suggest changes in cytoskeletal organisation. The findings confirm that the primary visual cortex shows molecular alterations in schizophrenia and extend the evidence for a widespread, rather than focal, cortical pathophysiology. PMID- 22675525 TI - A LOV protein modulates the physiological attributes of Xanthomonas axonopodis pv. citri relevant for host plant colonization. AB - Recent studies have demonstrated that an appropriate light environment is required for the establishment of efficient vegetal resistance responses in several plant-pathogen interactions. The photoreceptors implicated in such responses are mainly those belonging to the phytochrome family. Data obtained from bacterial genome sequences revealed the presence of photosensory proteins of the BLUF (Blue Light sensing Using FAD), LOV (Light, Oxygen, Voltage) and phytochrome families with no known functions. Xanthomonas axonopodis pv. citri is a Gram-negative bacterium responsible for citrus canker. The in silico analysis of the X. axonopodis pv. citri genome sequence revealed the presence of a gene encoding a putative LOV photoreceptor, in addition to two genes encoding BLUF proteins. This suggests that blue light sensing could play a role in X. axonopodis pv. citri physiology. We obtained the recombinant Xac-LOV protein by expression in Escherichia coli and performed a spectroscopic analysis of the purified protein, which demonstrated that it has a canonical LOV photochemistry. We also constructed a mutant strain of X. axonopodis pv. citri lacking the LOV protein and found that the loss of this protein altered bacterial motility, exopolysaccharide production and biofilm formation. Moreover, we observed that the adhesion of the mutant strain to abiotic and biotic surfaces was significantly diminished compared to the wild-type. Finally, inoculation of orange (Citrus sinensis) leaves with the mutant strain of X. axonopodis pv. citri resulted in marked differences in the development of symptoms in plant tissues relative to the wild-type, suggesting a role for the Xac-LOV protein in the pathogenic process. Altogether, these results suggest the novel involvement of a photosensory system in the regulation of physiological attributes of a phytopathogenic bacterium. A functional blue light receptor in Xanthomonas spp. has been described for the first time, showing an important role in virulence during citrus canker disease. PMID- 22675526 TI - What ecological factors shape species-area curves in neutral models? AB - Understanding factors that shape biodiversity and species coexistence across scales is of utmost importance in ecology, both theoretically and for conservation policies. Species-area relationships (SARs), measuring how the number of observed species increases upon enlarging the sampled area, constitute a convenient tool for quantifying the spatial structure of biodiversity. While general features of species-area curves are quite universal across ecosystems, some quantitative aspects can change significantly. Several attempts have been made to link these variations to ecological forces. Within the framework of spatially explicit neutral models, here we scrutinize the effect of varying the local population size (i.e. the number of individuals per site) and the level of habitat saturation (allowing for empty sites). We conclude that species-area curves become shallower when the local population size increases, while habitat saturation, unless strongly violated, plays a marginal role. Our findings provide a plausible explanation of why SARs for microorganisms are flatter than those for larger organisms. PMID- 22675527 TI - The effects of FreeSurfer version, workstation type, and Macintosh operating system version on anatomical volume and cortical thickness measurements. AB - FreeSurfer is a popular software package to measure cortical thickness and volume of neuroanatomical structures. However, little if any is known about measurement reliability across various data processing conditions. Using a set of 30 anatomical T1-weighted 3T MRI scans, we investigated the effects of data processing variables such as FreeSurfer version (v4.3.1, v4.5.0, and v5.0.0), workstation (Macintosh and Hewlett-Packard), and Macintosh operating system version (OSX 10.5 and OSX 10.6). Significant differences were revealed between FreeSurfer version v5.0.0 and the two earlier versions. These differences were on average 8.8 +/- 6.6% (range 1.3-64.0%) (volume) and 2.8 +/- 1.3% (1.1-7.7%) (cortical thickness). About a factor two smaller differences were detected between Macintosh and Hewlett-Packard workstations and between OSX 10.5 and OSX 10.6. The observed differences are similar in magnitude as effect sizes reported in accuracy evaluations and neurodegenerative studies.The main conclusion is that in the context of an ongoing study, users are discouraged to update to a new major release of either FreeSurfer or operating system or to switch to a different type of workstation without repeating the analysis; results thus give a quantitative support to successive recommendations stated by FreeSurfer developers over the years. Moreover, in view of the large and significant cross version differences, it is concluded that formal assessment of the accuracy of FreeSurfer is desirable. PMID- 22675528 TI - Novel evidence of HBV recombination in family cluster infections in western China. AB - Two hepatitis B virus (HBV) C/D recombinants were isolated from western China. No direct evidence indicates that these new viruses arose as a result of recombination between genotype C and D or a result of convergence. In this study, we search for evidence of intra-individual recombination in the family cluster cases with co-circulation of genotype C, D and C/D recombinants. We studied 68 individuals from 15 families with HBV infections in 2006, identified individuals with mixed HBV genotype co-infections by restriction fragment length polymorphism and proceeded with cloning and DNA sequencing. Recombination signals were detected by RDP3 software and confirmed by split phylogenetic trees. Families with mixed HBV genotype co-infections were resampled in 2007. Three of 15 families had individuals with different HBV genotype co-infections in 2006. One individual (Y2) had a triple infection of HBV genotype C, D and C/D recombinant in 2006, but only genotype D in 2007. Further clonal analysis of this patient indicated that the C/D recombinant was not identical to previously isolated CD1 or CD2, but many novel recombinants with C2, D1 and CD1 were simultaneously found. All parental strains could recombine with each other to form new recombinant in this patient. This indicates that the detectable mixed infection and recombination have a limited time window. Also, as the recombinant nature of HBV precludes the possibility of a simple phylogenetic taxonomy, a new standard may be required for classifying HBV sequences. PMID- 22675529 TI - Optimisation of over-expression in E. coli and biophysical characterisation of human membrane protein synaptogyrin 1. AB - Progress in functional and structural studies of integral membrane proteins (IMPs) is lacking behind their soluble counterparts due to the great challenge in producing stable and homogeneous IMPs. Low natural abundance, toxicity when over expressed and potential lipid requirements of IMPs are only a few reasons for the limited progress. Here, we describe an optimised workflow for the recombinant over-expression of the human tetraspan vesicle protein (TVP) synaptogyrin in Escherichia coli and its biophysical characterisation. TVPs are ubiquitous and abundant components of vesicles. They are believed to be involved in various aspects of the synaptic vesicle cycle, including vesicle biogenesis, exocytosis and endocytotic recycling. Even though TVPs are found in most cell types, high resolution structural information for this class of membrane proteins is still missing. The optimisation of the N-terminal sequence of the gene together with the usage of the recently developed Lemo21(DE3) strain which allows the balancing of the translation with the membrane insertion rate led to a 50-fold increased expression rate compared to the classical BL21(DE3) strain. The protein was soluble and stable in a variety of mild detergents and multiple biophysical methods confirmed the folded state of the protein. Crosslinking experiments suggest an oligomeric architecture of at least four subunits. The protein stability is significantly improved in the presence of cholesteryl hemisuccinate as judged by differential light scattering. The approach described here can easily be adapted to other eukaryotic IMPs. PMID- 22675530 TI - Low levels of cell-free circulating miR-361-3p and miR-625* as blood-based markers for discriminating malignant from benign lung tumors. AB - The high mortality rate of lung cancer patients is mainly due to the late stage at which lung cancer is diagnosed. For effective cancer prevention programs and early diagnosis, better blood-based markers are needed. Hence, blood-based microarray profiling of microRNA (miR) expression was performed in preoperative serum of 21 non-small cell lung cancer (NSCLC) patients and 11 healthy individuals by microfluid biochips containing 1158 different miRs. Two out of the 30 most dysregulated miRs were further validated in serum of 97 NSCLC patients, 20 patients with benign lung diseases and 30 healthy individuals by TaqMan MicroRNA Assays. Microarray profiling showed that miR-361-3p and miR-625* were significantly down-regulated in serum of lung cancer patients. Their further evaluation by quantitative RT-PCR showed that the levels of miR-361-3p and miR 625* were lower in NSCLC than in benign disease (p = 0.0001) and healthy individuals (p = 0.0001, p = 0.0005, respectively). Moreover, the levels of miR 625* were significantly lower in patients with large cell lung cancer (LCLC, p = 0.014) and smoking patients (p = 0.030) than in patients with adenocarcinoma and non-smoking patients, respectively. A rise in the levels of both miRs was observed in the postoperative samples compared with the preoperative levels (p = 0.0001). Functional analyses showed that Smad2 and TGFbeta1 are not dysregulated by miR-361-3p and miR-625* in the lung cell line A549, respectively. Our present pilot study suggests that miR-361-3p and miR-625* might have a protective influence on the development of NSCLC, and the quantitative assessment of these miRs in blood serum might have diagnostic potential to detect NSCLC, in particular in smokers. PMID- 22675531 TI - Genetic diversity, morphological uniformity and polyketide production in dinoflagellates (Amphidinium, Dinoflagellata). AB - Dinoflagellates are an intriguing group of eukaryotes, showing many unusual morphological and genetic features. Some groups of dinoflagellates are morphologically highly uniform, despite indications of genetic diversity. The species Amphidinium carterae is abundant and cosmopolitan in marine environments, grows easily in culture, and has therefore been used as a 'model' dinoflagellate in research into dinoflagellate genetics, polyketide production and photosynthesis. We have investigated the diversity of 'cryptic' species of Amphidinium that are morphologically similar to A. carterae, including the very similar species Amphidinium massartii, based on light and electron microscopy, two nuclear gene regions (LSU rDNA and ITS rDNA) and one mitochondrial gene region (cytochrome b). We found that six genetically distinct cryptic species (clades) exist within the species A. massartii and four within A. carterae, and that these clades differ from one another in molecular sequences at levels comparable to other dinoflagellate species, genera or even families. Using primers based on an alignment of alveolate ketosynthase sequences, we isolated partial ketosynthase genes from several Amphidinium species. We compared these genes to known dinoflagellate ketosynthase genes and investigated the evolution and diversity of the strains of Amphidinium that produce them. PMID- 22675533 TI - Disease-related cardiac troponins alter thin filament Ca2+ association and dissociation rates. AB - The contractile response of the heart can be altered by disease-related protein modifications to numerous contractile proteins. By utilizing an IAANS labeled fluorescent troponin C, [Formula: see text], we examined the effects of ten disease-related troponin modifications on the Ca(2+) binding properties of the troponin complex and the reconstituted thin filament. The selected modifications are associated with a broad range of cardiac diseases: three subtypes of familial cardiomyopathies (dilated, hypertrophic and restrictive) and ischemia-reperfusion injury. Consistent with previous studies, the majority of the protein modifications had no effect on the Ca(2+) binding properties of the isolated troponin complex. However, when incorporated into the thin filament, dilated cardiomyopathy mutations desensitized (up to 3.3-fold), while hypertrophic and restrictive cardiomyopathy mutations, and ischemia-induced truncation of troponin I, sensitized the thin filament to Ca(2+) (up to 6.3-fold). Kinetically, the dilated cardiomyopathy mutations increased the rate of Ca(2+) dissociation from the thin filament (up to 2.5-fold), while the hypertrophic and restrictive cardiomyopathy mutations, and the ischemia-induced truncation of troponin I decreased the rate (up to 2-fold). The protein modifications also increased (up to 5.4-fold) or decreased (up to 2.5-fold) the apparent rate of Ca(2+) association to the thin filament. Thus, the disease-related protein modifications alter Ca(2+) binding by influencing both the association and dissociation rates of thin filament Ca(2+) exchange. These alterations in Ca(2+) exchange kinetics influenced the response of the thin filament to artificial Ca(2+) transients generated in a stopped-flow apparatus. Troponin C may act as a hub, sensing physiological and pathological stimuli to modulate the Ca(2+)-binding properties of the thin filament and influence the contractile performance of the heart. PMID- 22675532 TI - Subcapsular sinus macrophage fragmentation and CD169+ bleb acquisition by closely associated IL-17-committed innate-like lymphocytes. AB - Subcapsular sinus macrophages (SSMs) in lymph nodes are rapidly exposed to antigens arriving in afferent lymph and have a role in their capture and display to B cells. In tissue sections SSMs exhibit long cellular processes and express high amounts of CD169. Here, we show that many of the cells present in lymph node cell suspensions that stain for CD169 are not macrophages but lymphocytes that have acquired SSM-derived membrane blebs. The CD169 bleb(+) lymphocytes are enriched for IL-17 committed IL-7Ralpha(hi)CCR6(+) T cells and NK cells. In addition, the CD169 staining detected on small numbers of CD11c(hi) dendritic cells is frequently associated with membrane blebs. Counter intuitively the CD169 bleb(+) lymphocytes are mostly CD4 and CD8 negative whereas many SSMs express CD4. In situ, many IL-7Ralpha(hi) cells are present at the subcapsular sinus and interfollicular regions and migrate in close association with CD169(+) macrophages. These findings suggest SSMs undergo fragmentation during tissue preparation and release blebs that are acquired by closely associated cells. They also suggest an intimate crosstalk between SSMs and IL-17 committed innate-like lymphocytes that may help provide early protection of the lymph node against lymph-borne invaders. PMID- 22675534 TI - The two-component sensor kinase TcsC and its role in stress resistance of the human-pathogenic mold Aspergillus fumigatus. AB - Two-component signaling systems are widespread in bacteria, but also found in fungi. In this study, we have characterized TcsC, the only Group III two component sensor kinase of Aspergillus fumigatus. TcsC is required for growth under hyperosmotic stress, but dispensable for normal growth, sporulation and conidial viability. A characteristic feature of the DeltatcsC mutant is its resistance to certain fungicides, like fludioxonil. Both hyperosmotic stress and treatment with fludioxonil result in a TcsC-dependent phosphorylation of SakA, the final MAP kinase in the high osmolarity glycerol (HOG) pathway, confirming a role for TcsC in this signaling pathway. In wild type cells fludioxonil induces a TcsC-dependent swelling and a complete, but reversible block of growth and cytokinesis. Several types of stress, such as hypoxia, exposure to farnesol or elevated concentrations of certain divalent cations, trigger a differentiation in A. fumigatus toward a "fluffy" growth phenotype resulting in white, dome-shaped colonies. The DeltatcsC mutant is clearly more susceptible to these morphogenetic changes suggesting that TcsC normally antagonizes this process. Although TcsC plays a role in the adaptation of A. fumigatus to hypoxia, it seems to be dispensable for virulence. PMID- 22675535 TI - Education and dementia in the context of the cognitive reserve hypothesis: a systematic review with meta-analyses and qualitative analyses. AB - BACKGROUND: Cognitive reserve (CR) or brain reserve capacity explains why individuals with higher IQ, education, or occupational attainment have lower risks of developing dementia, Alzheimer's disease (AD) or vascular dementia (VaD). The CR hypothesis postulates that CR reduces the prevalence and incidence of AD or VaD. It also hypothesizes that among those who have greater initial cognitive reserve (in contrast to those with less reserve) greater brain pathology occurs before the clinical symptoms of disease becomes manifest. Thus clinical disease onset triggers a faster decline in cognition and function, and increased mortality among those with initial greater cognitive reserve. Disease progression follows distinctly separate pathological and clinical paths. With education as a proxy we use meta-analyses and qualitative analyses to review the evidence for the CR hypothesis. METHODOLOGY/PRINCIPAL FINDINGS: We searched PubMed, PsycoINFO, EMBASE, HealthStar, and Scopus databases from January 1980 to June 2011 for observational studies with clear criteria for dementia, AD or VaD and education. One hundred and thirty-three articles with a variety of study designs met the inclusion criteria. Prevalence and incidence studies with odds ratios (ORs), relative risks or original data were included in the meta-analyses. Other studies were reviewed qualitatively. The studies covered 437,477 subjects. Prevalence and incidence studies with pooled ORs of 2.61 (95%CI 2.21-3.07) and 1.88 (95%CI 1.51-2.34) respectively, showed low education increased the risk of dementia. Heterogeneity and sensitivity tests confirmed the evidence. Generally, study characteristics had no effect on conclusions. Qualitative analyses also showed the protective effects of higher education on developing dementia and with clinical disease onset hastening a decline in cognition and function, and greater brain pathology. CONCLUSION/SIGNIFICANCE: This systematic review and meta analyses covering a wide range of observational studies and diverse settings provides robust support for the CR hypothesis. The CR hypothesis suggests several avenues for dementia prevention. PMID- 22675536 TI - Characterization of a conserved interaction between DNA glycosylase and ParA in Mycobacterium smegmatis and M. tuberculosis. AB - The chromosome partitioning proteins, ParAB, ensure accurate segregation of genetic materials into daughter cells and most bacterial species contain their homologs. However, little is known about the regulation of ParAB proteins. In this study, we found that 3-methyladenine DNA glycosylase I MsTAG(Ms5082) regulates bacterial growth and cell morphology by directly interacting with MsParA (Ms6939) and inhibiting its ATPase activity in Mycobacterium smegmatis. Using bacterial two-hybrid and pull-down techniques in combination with co immunoprecipitation assays, we show that MsTAG physically interacts with MsParA both in vitro and in vivo. Expression of MsTAG under conditions of DNA damage induction exhibited similar inhibition of growth as the deletion of the parA gene in M. smegmatis. Further, the effect of MsTAG on mycobacterial growth was found to be independent of its DNA glycosylase activity, and to result instead from direct inhibition of the ATPase activity of MsParA. Co-expression of these two proteins could counteract the growth defect phenotypes observed in strains overexpressing MsTAG alone in response to DNA damage induction. Based on protein co-expression and fluorescent co-localization assays, MsParA and MsTAG were further found to co-localize in mycobacterial cells. In addition, the interaction between the DNA glycosylase and ParA, and the regulation of ParA by the glycosylase were conserved in M. tuberculosis and M. smegmatis. Our findings provide important new insights into the regulatory mechanism of cell growth and division in mycobacteria. PMID- 22675537 TI - In vivo detection of amyloid-beta deposits using heavy chain antibody fragments in a transgenic mouse model for Alzheimer's disease. AB - This study investigated the in vivo properties of two heavy chain antibody fragments (V(H)H), ni3A and pa2H, to differentially detect vascular or parenchymal amyloid-beta deposits characteristic for Alzheimer's disease and cerebral amyloid angiopathy. Blood clearance and biodistribution including brain uptake were assessed by bolus injection of radiolabeled V(H)H in APP/PS1 mice or wildtype littermates. In addition, in vivo specificity for Abeta was examined in more detail with fluorescently labeled V(H)H by circumventing the blood-brain barrier via direct application or intracarotid co-injection with mannitol. All V(H)H showed rapid renal clearance (10-20 min). Twenty-four hours post-injection (99m)Tc-pa2H resulted in a small yet significant higher cerebral uptake in the APP/PS1 animals. No difference in brain uptake were observed for (99m)Tc-ni3A or DTPA((111)In)-pa2H, which lacked additional peptide tags to investigate further clinical applicability. In vivo specificity for Abeta was confirmed for both fluorescently labeled V(H)H, where pa2H remained readily detectable for 24 hours or more after injection. Furthermore, both V(H)H showed affinity for parenchymal and vascular deposits, this in contrast to human tissue, where ni3A specifically targeted only vascular Abeta. Despite a brain uptake that is as yet too low for in vivo imaging, this study provides evidence that V(H)H detect Abeta deposits in vivo, with high selectivity and favorable in vivo characteristics, making them promising tools for further development as diagnostic agents for the distinctive detection of different Abeta deposits. PMID- 22675539 TI - How past and present influence the foraging of clonal plants? AB - Clonal plants spreading horizontally and forming a network structure of ramets exhibit complex growth patterns to maximize resource uptake from the environment. They respond to spatial heterogeneity by changing their internode length or branching frequency. Ramets definitively root in the soil but stay interconnected for a varying period of time thus allowing an exchange of spatial and temporal information. We quantified the foraging response of clonal plants depending on the local soil quality sampled by the rooting ramet (i.e. the present information) and the resource variability sampled by the older ramets (i.e. the past information). We demonstrated that two related species, Potentilla reptans and P. anserina, responded similarly to the local quality of their environment by decreasing their internode length in response to nutrient-rich soil. Only P. reptans responded to resource variability by decreasing its internode length. In both species, the experience acquired by older ramets influenced the plastic response of new rooted ramets: the internode length between ramets depended not only on the soil quality locally sampled but also on the soil quality previously sampled by older ramets. We quantified the effect of the information perceived at different time and space on the foraging behavior of clonal plants by showing a non-linear response of the ramet rooting in the soil of a given quality. These data suggest that the decision to grow a stolon or to root a ramet at a given distance from the older ramet results from the integration of the past and present information about the richness and the variability of the environment. PMID- 22675538 TI - Genome haploidisation with chromosome 7 retention in oncocytic follicular thyroid carcinoma. AB - BACKGROUND: Recurrent non-medullary thyroid carcinoma (NMTC) is a rare disease. We initially characterized 27 recurrent NMTC: 13 papillary thyroid cancers (PTC), 10 oncocytic follicular carcinomas (FTC-OV), and 4 non-oncocytic follicular carcinomas (FTC). A validation cohort composed of benign and malignant (both recurrent and non-recurrent) thyroid tumours was subsequently analysed (n = 20). METHODS: Data from genome-wide SNP arrays and flow cytometry were combined to determine the chromosomal dosage (allelic state) in these tumours, including mutation analysis of components of PIK3CA/AKT and MAPK pathways. RESULTS: All FTC OVs showed a very distinct pattern of genomic alterations. Ten out of 10 FTC-OV cases showed near-haploidisation with or without subsequent genome endoreduplication. Near-haploidisation was seen in 5/10 as extensive chromosome wide monosomy (allelic state [A]) with near-haploid DNA indices and retention of especially chromosome 7 (seen as a heterozygous allelic state [AB]). In the remaining 5/10 chromosomal allelic states AA with near diploid DNA indices were seen with allelic state AABB of chromosome 7, suggesting endoreduplication after preceding haploidisation. The latter was supported by the presence of both near haploid and endoreduplicated tumour fractions in some of the cases. Results were confirmed using FISH analysis. Relatively to FTC-OV limited numbers of genomic alterations were identified in other types of recurrent NMTC studied, except for chromosome 22q which showed alterations in 6 of 13 PTCs. Only two HRAS, but no mutations of EGFR or BRAF were found in FTC-OV. The validation cohort showed two additional tumours with the distinct pattern of genomic alterations (both with oncocytic features and recurrent). CONCLUSIONS: We demonstrate that recurrent FTC OV is frequently characterised by genome-wide DNA haploidisation, heterozygous retention of chromosome 7, and endoreduplication of a near-haploid genome. Whether normal gene dosage on especially chromosome 7 (containing EGFR, BRAF, cMET) is crucial for FTC-OV tumour survival is an important topic for future research. MICROARRAYS: Data are made available at GEO (GSE31828). PMID- 22675540 TI - Formation of trans-activation competent HIV-1 Rev:RRE complexes requires the recruitment of multiple protein activation domains. AB - The HIV-1 Rev trans-activator is a nucleocytoplasmic shuttle protein that is essential for virus replication. Rev directly binds to unspliced and incompletely spliced viral RNA via the cis-acting Rev Response Element (RRE) sequence. Subsequently, Rev oligomerizes cooperatively and interacts with the cellular nuclear export receptor CRM1. In addition to mediating nuclear RNA export, Rev also affects the stability, translation and packaging of Rev-bound viral transcripts. Although it is established that Rev function requires the multimeric assembly of Rev molecules on the RRE, relatively little is known about how many Rev monomers are sufficient to form a trans-activation competent Rev:RRE complex, or which specific activity of Rev is affected by its oligomerization. We here analyzed by functional studies how homooligomer formation of Rev affects the trans-activation capacity of this essential HIV-1 regulatory protein. In a gain of-function approach, we fused various heterologous dimerization domains to an otherwise oligomerization-defective Rev mutant and were able to demonstrate that oligomerization of Rev is not required per se for the nuclear export of this viral trans-activator. In contrast, however, the formation of Rev oligomers on the RRE is a precondition to trans-activation by directly affecting the nuclear export of Rev-regulated mRNA. Moreover, experimental evidence is provided showing that at least two protein activation domains are required for the formation of trans-activation competent Rev:RRE complexes. The presented data further refine the model of Rev trans-activation by directly demonstrating that Rev oligomerization on the RRE, thereby recruiting at least two protein activation domains, is required for nuclear export of unspliced and incompletely spliced viral RNA. PMID- 22675541 TI - Benefits and pitfalls of secondary antibodies: why choosing the right secondary is of primary importance. AB - Simultaneous labeling of multiple targets in a single sample, or multiplexing, is a powerful approach to directly compare the amount, localization and/or molecular properties of different targets in the same sample. Here we highlight the robust reliability of the simultaneous use of multiple mouse monoclonal antibodies (mAbs) of different immunoglobulin G (IgG) subclasses in a wide variety of multiplexing applications employing anti-mouse IgG subclass-specific secondary antibodies (2 degrees Abs). We also describe the unexpected finding that IgG subclass-specific 2 degrees Abs are superior to general anti-mouse IgG 2 degrees Abs in every tested application in which mouse mAbs were used. This was due to a detection bias of general anti-mouse IgG-specific 2 degrees Abs against mAbs of the most common mouse IgG subclass, IgG1, and to a lesser extent IgG2b mAbs. Thus, when using any of numerous mouse mAbs available through commercial and non profit sources, for cleaner and more robust results each mAb should be detected with its respective IgG subclass-specific 2 degrees Ab and not a general anti mouse IgG-specific 2 degrees Ab. PMID- 22675542 TI - Diarrhoea complicating severe acute malnutrition in Kenyan children: a prospective descriptive study of risk factors and outcome. AB - BACKGROUND: Severe acute malnutrition (SAM) accounts for two million deaths worldwide annually. In those hospitalised with SAM, concomitant infections and diarrhoea are frequent complications resulting in adverse outcome. We examined the clinical and laboratory features on admission and outcome of children with SAM and diarrhoea at a Kenyan district hospital. METHODS: A 4-year prospective descriptive study involving 1,206 children aged 6 months to 12 years, hospitalized with SAM and managed in accordance with WHO guidelines. Data on clinical features, haematological, biochemical and microbiological findings for children with diarrhoea (>= 3 watery stools/day) were systematically collected and analyzed to identify risk factors associated with poor outcome. RESULTS: At admission 592 children (49%) had diarrhoea of which 122 (21%) died compared to 72/614 (12%) deaths in those without diarrhoea at admission (Chi(2) = 17.6 p<0.001). A further 187 (16%) children developed diarrhoea after 48 hours of admission and 33 died (18%). Any diarrhoea during admission resulted in a significantly higher mortality 161/852 (19%) than those uncomplicated by diarrhoea 33/351 (9%) (Chi(2) = 16.6 p<0.001). Features associated with a fatal outcome in children presenting with diarrhoea included bacteraemia, hyponatraemia, low mid-upper arm circumference <10 cm, hypoxia, hypokalaemia and oedema. Bacteraemia had the highest risk of death (adjusted OR 6.1; 95% C.I 2.3, 16.3 p<0.001); and complicated 24 (20%) of fatalities. Positive HIV antibody status was more frequent in cases with diarrhoea at admission (23%) than those without (15%, Chi(2) = 12.0 p = 0.001) but did not increase the risk of death in diarrhoea cases. CONCLUSION: Children with SAM complicated by diarrhoea had a higher risk of death than those who did not have diarrhoea during their hospital stay. Further operational and clinical research is needed to reduce mortality in children with SAM in the given setting. PMID- 22675543 TI - Apelin enhances directed cardiac differentiation of mouse and human embryonic stem cells. AB - Apelin is a peptide ligand for an orphan G-protein coupled receptor (APJ receptor) and serves as a critical gradient for migration of mesodermal cells fated to contribute to the myocardial lineage. The present study was designed to establish a robust cardiac differentiation protocol, specifically, to evaluate the effect of apelin on directed differentiation of mouse and human embryonic stem cells (mESCs and hESCs) into cardiac lineage. Different concentrations of apelin (50, 100, 500 nM) were evaluated to determine its differentiation potential. The optimized dose of apelin was then combined with mesodermal differentiation factors, including BMP-4, activin-A, and bFGF, in a developmentally specific temporal sequence to examine the synergistic effects on cardiac differentiation. Cellular, molecular, and physiologic characteristics of the apelin-induced contractile embryoid bodies (EBs) were analyzed. It was found that 100 nM apelin resulted in highest percentage of contractile EB for mESCs while 500 nM had the highest effects on hESCs. Functionally, the contractile frequency of mESCs-derived EBs (mEBs) responded appropriately to increasing concentration of isoprenaline and diltiazem. Positive phenotype of cardiac specific markers was confirmed in the apelin-treated groups. The protocol, consisting of apelin and mesodermal differentiation factors, induced contractility in significantly higher percentage of hESC-derived EBs (hEBs), up regulated cardiac-specific genes and cell surface markers, and increased the contractile force. In conclusion, we have demonstrated that the treatment of apelin enhanced cardiac differentiation of mouse and human ESCs and exhibited synergistic effects with mesodermal differentiation factors. PMID- 22675544 TI - Fine mapping of the Bsr1 barley stripe mosaic virus resistance gene in the model grass Brachypodium distachyon. AB - The ND18 strain of Barley stripe mosaic virus (BSMV) infects several lines of Brachypodium distachyon, a recently developed model system for genomics research in cereals. Among the inbred lines tested, Bd3-1 is highly resistant at 20 to 25 degrees C, whereas Bd21 is susceptible and infection results in an intense mosaic phenotype accompanied by high levels of replicating virus. We generated an F(6:7) recombinant inbred line (RIL) population from a cross between Bd3-1 and Bd21 and used the RILs, and an F(2) population of a second Bd21 * Bd3-1 cross to evaluate the inheritance of resistance. The results indicate that resistance segregates as expected for a single dominant gene, which we have designated Barley stripe mosaic virus resistance 1 (Bsr1). We constructed a genetic linkage map of the RIL population using SNP markers to map this gene to within 705 Kb of the distal end of the top of chromosome 3. Additional CAPS and Indel markers were used to fine map Bsr1 to a 23 Kb interval containing five putative genes. Our study demonstrates the power of using RILs to rapidly map the genetic determinants of BSMV resistance in Brachypodium. Moreover, the RILs and their associated genetic map, when combined with the complete genomic sequence of Brachypodium, provide new resources for genetic analyses of many other traits. PMID- 22675545 TI - Decrypting the mitochondrial gene pool of modern Panamanians. AB - The Isthmus of Panama--the narrow neck of land connecting the northern and southern American landmasses--was an obligatory corridor for the Paleo-Indians as they moved into South America. Archaeological evidence suggests an unbroken link between modern natives and their Paleo-Indian ancestors in some areas of Panama, even if the surviving indigenous groups account for only 12.3% of the total population. To evaluate if modern Panamanians have retained a larger fraction of the native pre-Columbian gene pool in their maternally-inherited mitochondrial genome, DNA samples and historical records were collected from more than 1500 volunteer participants living in the nine provinces and four indigenous territories of the Republic. Due to recent gene-flow, we detected ~14% African mitochondrial lineages, confirming the demographic impact of the Atlantic slave trade and subsequent African immigration into Panama from Caribbean islands, and a small European (~2%) component, indicating only a minor influence of colonialism on the maternal side. The majority (~83%) of Panamanian mtDNAs clustered into native pan-American lineages, mostly represented by haplogroup A2 (51%). These findings reveal an overwhelming native maternal legacy in today's Panama, which is in contrast with the overall concept of personal identity shared by many Panamanians. Moreover, the A2 sub-clades A2ad and A2af (with the previously named 6 bp Huetar deletion), when analyzed at the maximum level of resolution (26 entire mitochondrial genomes), confirm the major role of the Pacific coastal path in the peopling of North, Central and South America, and testify to the antiquity of native mitochondrial genomes in Panama. PMID- 22675546 TI - E3-14.7K is recruited to TNF-receptor 1 and blocks TNF cytolysis independent from interaction with optineurin. AB - Escape from the host immune system is essential for intracellular pathogens. The adenoviral protein E3-14.7K (14.7K) is known as a general inhibitor of tumor necrosis factor (TNF)-induced apoptosis. It efficiently blocks TNF-receptor 1 (TNFR1) internalization but the underlying molecular mechanism still remains elusive. Direct interaction of 14.7K and/or associated proteins with the TNFR1 complex has been discussed although to date not proven. In our study, we provide for the first time evidence for recruitment of 14.7K and the 14.7K interacting protein optineurin to TNFR1. Various functions have been implicated for optineurin such as regulation of receptor endocytosis, vesicle trafficking, regulation of the nuclear factor kappaB (NF-kappaB) pathway and antiviral signaling. We therefore hypothesized that binding of optineurin to 14.7K and recruitment of both proteins to the TNFR1 complex is essential for protection against TNF-induced cytotoxic effects. To precisely dissect the individual role of 14.7K and optineurin, we generated and characterized a 14.7K mutant that does not confer TNF-resistance but is still able to interact with optineurin. In H1299 and KB cells expressing 14.7K wild-type protein, neither decrease in cell viability nor cleavage of caspases was observed upon stimulation with TNF. In sharp contrast, cells expressing the non-protective mutant of 14.7K displayed reduced viability and cleavage of initiator and effector caspases upon TNF treatment, indicating ongoing apoptotic cell death. Knockdown of optineurin in 14.7K expressing cells did not alter the protective effect as measured by cell viability and caspase activation. Taken together, we conclude that optineurin despite its substantial role in vesicular trafficking, endocytosis of cell surface receptors and recruitment to the TNFR1 complex is dispensable for the 14.7K-mediated protection against TNF-induced apoptosis. PMID- 22675547 TI - A novel strategy for selection and validation of reference genes in dynamic multidimensional experimental design in yeast. AB - BACKGROUND: Understanding the dynamic mechanism behind the transcriptional organization of genes in response to varying environmental conditions requires time-dependent data. The dynamic transcriptional response obtained by real-time RT-qPCR experiments could only be correctly interpreted if suitable reference genes are used in the analysis. The lack of available studies on the identification of candidate reference genes in dynamic gene expression studies necessitates the identification and the verification of a suitable gene set for the analysis of transient gene expression response. PRINCIPAL FINDINGS: In this study, a candidate reference gene set for RT-qPCR analysis of dynamic transcriptional changes in Saccharomyces cerevisiae was determined using 31 different publicly available time series transcriptome datasets. Ten of the twelve candidates (TPI1, FBA1, CCW12, CDC19, ADH1, PGK1, GCN4, PDC1, RPS26A and ARF1) we identified were not previously reported as potential reference genes. Our method also identified the commonly used reference genes ACT1 and TDH3. The most stable reference genes from this pool were determined as TPI1, FBA1, CDC19 and ACT1 in response to a perturbation in the amount of available glucose and as FBA1, TDH3, CCW12 and ACT1 in response to a perturbation in the amount of available ammonium. The use of these newly proposed gene sets outperformed the use of common reference genes in the determination of dynamic transcriptional response of the target genes, HAP4 and MEP2, in response to relaxation from glucose and ammonium limitations, respectively. CONCLUSIONS: A candidate reference gene set to be used in dynamic real-time RT-qPCR expression profiling in yeast was proposed for the first time in the present study. Suitable pools of stable reference genes to be used under different experimental conditions could be selected from this candidate set in order to successfully determine the expression profiles for the genes of interest. PMID- 22675548 TI - Persistently elevated right ventricular index of myocardial performance in preterm infants with incipient bronchopulmonary dysplasia. AB - OBJECTIVES: Elevated pulmonary vascular resistance occurs during the first days after birth in all newborn infants and persists in infants at risk for bronchopulmonary dysplasia (BPD). It is difficult to measure in a non-invasive fashion. We assessed the usefulness of the right ventricular index of myocardial performance (RIMP) to estimate pulmonary vascular resistance in very low birth weight infants. STUDY DESIGN: Prospective echocardiography on day of life (DOL) 2, 7, 14, and 28 in 121 preterm infants (median [quartiles] gestational age 28 [26]-[29] weeks, birth weight 998 [743-1225] g) of whom 36 developed BPD (oxygen supplementation at 36 postmenstrual weeks). RESULTS: RIMP derived by conventional pulsed Doppler technique was unrelated to heart rate or mean blood pressure. RIMP on DOL 2 was similar in infants who subsequently did (0.39 [0.33-0.55]) and did not develop BPD (0.39 [0.28-0.51], p = 0.467). RIMP declined steadily in non-BPD infants but not in BPD infants (DOL 7: 0.31[0.22-0.39] vs. 0.35[0.29-0.48], p = 0.014; DOL 14: 0.23[0.17-0.30] vs. 0.35[0.25-0.43], p<0.001; DOL 28: 0.21[0.15 0.28] vs. 0.31 [0.21-0.35], p = 0.015). CONCLUSIONS: In preterm infants, a decline in RIMP after birth was not observed in those with incipient BPD. The pattern of RIMP measured in preterm infants is commensurate with that of pulmonary vascular resistance. PMID- 22675549 TI - High-resolution in-vivo analysis of normal brain response to cranial irradiation. AB - Radiation therapy (RT) is a widely accepted treatment strategy for many central nervous system (CNS) pathologies. However, despite recognized therapeutic success, significant negative consequences are associated with cranial irradiation (CR), which manifests months to years post-RT. The pathophysiology and molecular alterations that culminate in the long-term detrimental effects of CR are poorly understood, though it is thought that endothelial injury plays a pivotal role in triggering cranial injury. We therefore explored the contribution of bone marrow derived cells (BMDCs) in their capacity to repair and contribute to neo-vascularization following CR. Using high-resolution in vivo optical imaging we have studied, at single-cell resolution, the spatio-temporal response of BMDCs in normal brain following CR. We demonstrate that BMDCs are recruited specifically to the site of CR, in a radiation dose and temporal-spatial manner. We establish that BMDCs do not form endothelial cells but rather they differentiate predominantly into inflammatory cells and microglia. Most notably we provide evidence that more than 50% of the microglia in the irradiated region of the brain are not resident microglia but recruited from the bone marrow following CR. These results have invaluable therapeutic implications as BMDCs may be a primary therapeutic target to block acute and long-term inflammatory response following CR. Identifying the critical steps involved in the sustained recruitment and differentiation of BMDCs into microglia at the site of CR can provide new insights into the mechanisms of injury following CR offering potential therapeutic strategies to counteract the long-term adverse effects of CR. PMID- 22675551 TI - Association between proximity to a health center and early childhood mortality in Madagascar. AB - OBJECTIVE: To evaluate the association between proximity to a health center and early childhood mortality in Madagascar, and to assess the influence of household wealth, maternal educational attainment, and maternal health on the effects of distance. METHODS: From birth records of subjects in the Demographic and Health Survey, we identified 12565 singleton births from January 2004 to August 2009. After excluding 220 births that lacked global positioning system information for exposure assessment, odds ratios (ORs) and their 95% confidence intervals (CIs) for neonatal mortality and infant mortality were estimated using multilevel logistic regression models, with 12345 subjects (level 1), nested within 584 village locations (level 2), and in turn nested within 22 regions (level 3). We additionally stratified the subjects by the birth order. We estimated predicted probabilities of each outcome by a three-level model including cross-level interactions between proximity to a health center and household wealth, maternal educational attainment, and maternal anemia. RESULTS: Compared with those who lived >1.5-3.0 km from a health center, the risks for neonatal mortality and infant mortality tended to increase among those who lived further than 5.0 km from a health center; the adjusted ORs for neonatal mortality and infant mortality for those who lived >5.0-10.0 km away from a health center were 1.36 (95% CI: 0.92-2.01) and 1.42 (95% CI: 1.06-1.90), respectively. The positive associations were more pronounced among the second or later child. The distance effects were not modified by household wealth status, maternal educational attainment, or maternal health status. CONCLUSIONS: Our study suggests that distance from a health center is a risk factor for early childhood mortality (primarily, infant mortality) in Madagascar by using a large-scale nationally representative dataset. The accessibility to health care in remote areas would be a key factor to achieve better infant health. PMID- 22675550 TI - An interferon-related signature in the transcriptional core response of human macrophages to Mycobacterium tuberculosis infection. AB - The W-Beijing family of Mycobacterium tuberculosis (Mtb) strains is known for its high-prevalence and -virulence, as well as for its genetic diversity, as recently reported by our laboratories and others. However, little is known about how the immune system responds to these strains. To explore this issue, here we used reverse engineering and genome-wide expression profiling of human macrophage-like THP-1 cells infected by different Mtb strains of the W-Beijing family, as well as by the reference laboratory strain H37Rv. Detailed data mining revealed that host cell transcriptome responses to H37Rv and to different strains of the W-Beijing family are similar and overwhelmingly induced during Mtb infections, collectively typifying a robust gene expression signature ("THP1r2Mtb-induced signature"). Analysis of the putative transcription factor binding sites in promoter regions of genes in this signature identified several key regulators, namely STATs, IRF 1, IRF-7, and Oct-1, commonly involved in interferon-related immune responses. The THP1r2Mtb-induced signature appeared to be highly relevant to the interferon inducible signature recently reported in active pulmonary tuberculosis patients, as revealed by cross-signature and cross-module comparisons. Further analysis of the publicly available transcriptome data from human patients showed that the signature appears to be relevant to active pulmonary tuberculosis patients and their clinical therapy, and be tuberculosis specific. Thus, our results provide an additional layer of information at the transcriptome level on mechanisms involved in host macrophage response to Mtb, which may also implicate the robustness of the cellular defense system that can effectively fight against genetic heterogeneity in this pathogen. PMID- 22675552 TI - Thermostable DNA polymerase from a viral metagenome is a potent RT-PCR enzyme. AB - Viral metagenomic libraries are a promising but previously untapped source of new reagent enzymes. Deep sequencing and functional screening of viral metagenomic DNA from a near-boiling thermal pool identified clones expressing thermostable DNA polymerase (Pol) activity. Among these, 3173 Pol demonstrated both high thermostability and innate reverse transcriptase (RT) activity. We describe the biochemistry of 3173 Pol and report its use in single-enzyme reverse transcription PCR (RT-PCR). Wild-type 3173 Pol contains a proofreading 3'-5' exonuclease domain that confers high fidelity in PCR. An easier-to-use exonuclease-deficient derivative was incorporated into a PyroScript RT-PCR master mix and compared to one-enzyme (Tth) and two-enzyme (MMLV RT/Taq) RT-PCR systems for quantitative detection of MS2 RNA, influenza A RNA, and mRNA targets. Specificity and sensitivity of 3173 Pol-based RT-PCR were higher than Tth Pol and comparable to three common two-enzyme systems. The performance and simplified set up make this enzyme a potential alternative for research and molecular diagnostics. PMID- 22675553 TI - Hepatocyte growth factor increases osteopontin expression in human osteoblasts through PI3K, Akt, c-Src, and AP-1 signaling pathway. AB - BACKGROUND: Hepatocyte growth factor (HGF) has been demonstrated to stimulate osteoblast proliferation and participated bone remodeling. Osteopontin (OPN) is a secreted phosphoglycoprotein that belongs to the SIBLING family and is present during bone mineralization. However, the effects of HGF on OPN expression in human osteoblasts are large unknown. METHODOLOGY/PRINCIPAL FINDINGS: Here we found that HGF induced OPN expression in human osteoblasts dose-dependently. HGF mediated OPN production was attenuated by c-Met inhibitor and siRNA. Pretreatment of osteoblasts with PI3K inhibitor (Ly294002), Akt inhibitor, c-Src inhibitor (PP2), or AP-1 inhibitor (curcumin) blocked the potentiating action of HGF. Stimulation of osteoblasts with HGF enhanced PI3K, Akt, and c-Src activation. In addition, incubation of cells with HGF also increased c-Jun phosphorylation, AP-1 luciferase activity, and c-Jun binding to the AP-1 element on the OPN promoter. HGF-mediated AP-1-luciferase activity and c-Jun binding to the AP-1 element was reduced by c-Met inhibitor, Ly294002, Akt inhibitor, and PP2. CONCLUSIONS/SIGNIFICANCE: Our results suggest that the interaction between HGF and c-Met increases OPN expression in human osteoblasts via the PI3K, Akt, c-Src, c-Jun, and AP-1 signaling pathway. PMID- 22675554 TI - Tanshinone IIA attenuates the inflammatory response and apoptosis after traumatic injury of the spinal cord in adult rats. AB - BACKGROUND: Spinal cord injury (SCI), including immediate mechanical injury and secondary injury, is associated with the inflammatory response, apoptosis and oxidative stress in response to traumatic injury. Tanshinone IIA (TIIA) is one of the major extracts obtained from Salvia miltiorrhiza BUNGE, which has anti inflammatory and anti-apoptotic effects on many diseases. However, little is known about the effects of TIIA treatment on SCI. Therefore, the aim of the present study is to evaluate the pharmacological action of TIIA on secondary damage and the underlying mechanisms of experimental SCI in rats. METHODOLOGY/PRINCIPAL FINDINGS: SCI was generated using a weight drop device on the dorsal spinal cord via a two-level T9-T11 laminectomy. SCI in rats resulted in severe trauma, characterized by locomotor disturbance, edema, neutrophil infiltration, the production of astrocytes and inflammatory mediators, apoptosis and oxidative stress. TIIA treatment (20 mg/kg, i.p.) after SCI induced significant effects: (1) improved motor function (Basso, Beattie and Bresnahan scores), (2) reduced the degree of tissue injury (histological score), neutrophil infiltration (myeloperoxidase activity) and the expression of astrocytes, (3) inhibited the activation of SCI-related pathways, such as NF-kappaB and MAPK signaling pathways, (4) decreased the production of pro-inflammatory cytokines (TNF-alpha, IL-1beta, and IL-6) and iNOS, (5) reduced apoptosis (TUNEL staining, and Bcl-2 and caspase-3 expression) and (6) reversed the redox state imbalance. CONCLUSIONS/SIGNIFICANCE: The results clearly show that TIIA has a prominent protective effect against SCI through inhibiting the inflammatory response and apoptosis in the spinal cord tissue after SCI. PMID- 22675555 TI - Human cortical traveling waves: dynamical properties and correlations with responses. AB - The spatiotemporal behavior of human EEG oscillations is investigated. Traveling waves in the alpha and theta ranges are found to be common in both prestimulus and poststimulus EEG activity. The dynamical properties of these waves, including their speeds, directions, and durations, are systematically characterized for the first time, and the results show that there are significant changes of prestimulus spontaneous waves in the presence of an external stimulus. Furthermore, the functional relevance of these waves is examined by studying how they are correlated with reaction times on a single trial basis; prestimulus alpha waves traveling in the frontal-to-occipital direction are found to be most correlated to reaction speeds. These findings suggest that propagating waves of brain oscillations might be involved in mediating long-range interactions between widely distributed parts of human cortex. PMID- 22675557 TI - Precore mutation of hepatitis B virus may contribute to hepatocellular carcinoma risk: evidence from an updated meta-analysis. AB - BACKGROUND: Studies focused on the correlation of mutations in the genome of Hepatitis B Virus (HBV) like Pre-S mutation, Basal Core promoter (BCP), Enhancer II (EnhII), especially Precore mutation, with the risk of hepatocellular carcinoma (HCC) have triggered stiff controversies. With an increasing number of studies in this field recently, we conducted this meta-analysis to appraise the correlations. METHODS: We searched the commonly used databases both in English and Chinese till February 1(st), 2012. Meta-analysis was performed in fixed/random-effects models using STATA 10.0. Publication bias was examined through Egger's test and Begg's funnel plot. RESULTS: In total, 85 case-control studies were included involving 16745 HBV-infected patients, of whom 5781 had HCC. Statistically significant correlations were observed in Precore mutation G1896A (OR = 1.46, 95% confidence interval [CI] = 1.15-1.85, P(OR) = 0.002), G1899A (OR = 3.13, 95%CI = 2.38-4.13, P(OR)<0.001) and Pre-S mutation especially Pre-S1 deletion (OR = 2.94, 95%CI = 2.22 to 3.89) and Pre-S2 deletion (OR = 3.02, 95%CI = 2.03 to 4.50). Similar correlation existed between BCP double mutation A1762T/G1764A, T1753V, C1653T and HCC. In subgroup analysis, the Asians, genotype C or HBeAg positive patients with certain above mutations may be more susceptible to HCC. Besides, the mutations like G1896A and BCP double mutation may be associated with the progression of the liver diseases. CONCLUSIONS: Precore mutation G1896A, G1899A, deletions in Pre-S region as well as the other commonly seen mutations correlated with the increased risk of HCC, especially in Asians and may predict the progression of the liver disease. PMID- 22675556 TI - Central role of pyrophosphate in acellular cementum formation. AB - BACKGROUND: Inorganic pyrophosphate (PP(i)) is a physiologic inhibitor of hydroxyapatite mineral precipitation involved in regulating mineralized tissue development and pathologic calcification. Local levels of PP(i) are controlled by antagonistic functions of factors that decrease PP(i) and promote mineralization (tissue-nonspecific alkaline phosphatase, Alpl/TNAP), and those that increase local PP(i) and restrict mineralization (progressive ankylosis protein, ANK; ectonucleotide pyrophosphatase phosphodiesterase-1, NPP1). The cementum enveloping the tooth root is essential for tooth function by providing attachment to the surrounding bone via the nonmineralized periodontal ligament. At present, the developmental regulation of cementum remains poorly understood, hampering efforts for regeneration. To elucidate the role of PP(i) in cementum formation, we analyzed root development in knock-out ((-/-)) mice featuring PP(i) dysregulation. RESULTS: Excess PP(i) in the Alpl(-/-) mouse inhibited cementum formation, causing root detachment consistent with premature tooth loss in the human condition hypophosphatasia, though cementoblast phenotype was unperturbed. Deficient PP(i) in both Ank and Enpp1(-/-) mice significantly increased cementum apposition and overall thickness more than 12-fold vs. controls, while dentin and cellular cementum were unaltered. Though PP(i) regulators are widely expressed, cementoblasts selectively expressed greater ANK and NPP1 along the root surface, and dramatically increased ANK or NPP1 in models of reduced PP(i) output, in compensatory fashion. In vitro mechanistic studies confirmed that under low PP(i) mineralizing conditions, cementoblasts increased Ank (5-fold) and Enpp1 (20 fold), while increasing PP(i) inhibited mineralization and associated increases in Ank and Enpp1 mRNA. CONCLUSIONS: Results from these studies demonstrate a novel developmental regulation of acellular cementum, wherein cementoblasts tune cementogenesis by modulating local levels of PP(i), directing and regulating mineral apposition. These findings underscore developmental differences in acellular versus cellular cementum, and suggest new approaches for cementum regeneration. PMID- 22675558 TI - Functional characterization of a first avian cytochrome P450 of the CYP2D subfamily (CYP2D49). AB - The CYP2D family members are instrumental in the metabolism of 20-25% of commonly prescribed drugs. Although many CYP2D isoforms have been well characterized in other animal models, research concerning the chicken CYP2Ds is limited. In this study, a cDNA encoding a novel CYP2D enzyme (CYP2D49) was cloned from the chicken liver for the first time. The CYP2D49 cDNA contained an open reading frame of 502 amino acids that shared 52%-57% identities with other CYP2Ds. The gene structure and neighboring genes of CYP2D49 are conserved and similar to those of human CYP2D6. Additionally, similar to human CYP2D6, CYP2D49 is un-inducible in the liver and expressed predominantly in the liver, kidney and small intestine, with detectable levels in several other tissues. Metabolic assays of the CYP2D49 protein heterologously expressed in E. coli and Hela cells indicated that CYP2D49 metabolized the human CYP2D6 substrate, bufuralol, but not debrisoquine. Moreover, quinidine, a potent inhibitor of human CYP2D6, only inhibited the bufuralol 1'-hydroxylation activity of CYP2D49 to a negligible degree. All these results indicated that CYP2D49 had functional characteristics similar to those of human CYP2D6 but measurably differed in the debrisoquine 4'-hydroxylation and quinidine inhibitory profile. Further structure-function investigations that employed site-directed mutagenesis and circular dichroism spectroscopy identified the importance of Val-126, Glu-222, Asp-306, Phe-486 and Phe-488 in keeping the enzymatic activity of CYP2D49 toward bufuralol as well as the importance of Asp 306, Phe-486 and Phe-488 in maintaining the conformation of CYP2D49 protein. The current study is only the first step in characterizing the metabolic mechanism of CYP2D49; further studies are still required. PMID- 22675559 TI - Imidacloprid-induced impairment of mushroom bodies and behavior of the native stingless bee Melipona quadrifasciata anthidioides. AB - Declines in pollinator colonies represent a worldwide concern. The widespread use of agricultural pesticides is recognized as a potential cause of these declines. Previous studies have examined the effects of neonicotinoid insecticides such as imidacloprid on pollinator colonies, but these investigations have mainly focused on adult honey bees. Native stingless bees (Hymenoptera: Apidae: Meliponinae) are key pollinators in neotropical areas and are threatened with extinction due to deforestation and pesticide use. Few studies have directly investigated the effects of pesticides on these pollinators. Furthermore, the existing impact studies did not address the issue of larval ingestion of contaminated pollen and nectar, which could potentially have dire consequences for the colony. Here, we assessed the effects of imidacloprid ingestion by stingless bee larvae on their survival, development, neuromorphology and adult walking behavior. Increasing doses of imidacloprid were added to the diet provided to individual worker larvae of the stingless bee Melipona quadrifasciata anthidioides throughout their development. Survival rates above 50% were only observed at insecticide doses lower than 0.0056 ug active ingredient (a.i.)/bee. No sublethal effect on body mass or developmental time was observed in the surviving insects, but the pesticide treatment negatively affected the development of mushroom bodies in the brain and impaired the walking behavior of newly emerged adult workers. Therefore, stingless bee larvae are particularly susceptible to imidacloprid, as it caused both high mortality and sublethal effects that impaired brain development and compromised mobility at the young adult stage. These findings demonstrate the lethal effects of imidacloprid on native stingless bees and provide evidence of novel serious sublethal effects that may compromise colony survival. The ecological and economic importance of neotropical stingless bees as pollinators, their susceptibility to insecticides and the vulnerability of their larvae to insecticide exposure emphasize the importance of studying these species. PMID- 22675560 TI - Histological and molecular evaluation of patient-derived colorectal cancer explants. AB - Mouse models have been developed to investigate colorectal cancer etiology and evaluate new anti-cancer therapies. While genetically engineered and carcinogen induced mouse models have provided important information with regard to the mechanisms underlying the oncogenic process, tumor xenograft models remain the standard for the evaluation of new chemotherapy and targeted drug treatments for clinical use. However, it remains unclear to what extent explanted colorectal tumor tissues retain inherent pathological features over time. In this study, we have generated a panel of 27 patient-derived colorectal cancer explants (PDCCEs) by direct transplantation of human colorectal cancer tissues into NOD-SCID mice. Using this panel, we performed a comparison of histology, gene expression and mutation status between PDCCEs and the original human tissues from which they were derived. Our findings demonstrate that PDCCEs maintain key histological features, basic gene expression patterns and KRAS/BRAF mutation status through multiple passages. Altogether, these findings suggest that PDCCEs maintain similarity to the patient tumor from which they are derived and may have the potential to serve as a reliable preclinical model that can be incorporated into future strategies to optimize individual therapy for patients with colorectal cancer. PMID- 22675561 TI - Vital dye reaction and granule localization in periplasm of Escherichia coli. AB - BACKGROUND: Tetrazolium salts are widely used in biology as indicators of metabolic activity - hence termed vital dyes - but their reduction site is still debated despite decades of intensive research. The prototype, 2,3,5- triphenyl tetrazolium chloride, which was first synthesized a century ago, often generates a single formazan granule at the old pole of Escherichia coli cells after reduction. So far, no explanation for their pole localization has been proposed. METHOD/PRINCIPAL FINDINGS: Here we provide evidence that the granules form in the periplasm of bacterial cells. A source of reducing power is deduced to be thiol groups destined to become disulfides, since deletion of dsbA, coding for thiol oxidase, enhances the formation of reduced formazan. However, pervasive reduction did not result in a random distribution of formazan aggregates. In filamentous cells, large granules appear at regular intervals of about four normal cell lengths, consistent with a diffusion-to-capture model. Computer simulations of a minimal biophysical model showed that the pole localization of granules is a spontaneous process, i.e. small granules in a normal size bacterium have lower energy at the poles. This biased their diffusion to the poles. They kept growing there and eventually became fixed. CONCLUSIONS: We observed that formazan granules formed in the periplasm after reduction of tetrazolium, which calls for re-evaluation of previous studies using cell-free systems that liberate inaccessible intracellular reductant and potentially generate artifacts. The localization of formazan granules in E. coli cells can now be understood. In living bacteria, the seeds formed at or migrated to the new pole would become visible only when that new pole already became an old pole, because of the relatively slow growth rate of granules relative to cell division. PMID- 22675562 TI - Knockdown of the fat mass and obesity gene disrupts cellular energy balance in a cell-type specific manner. AB - Recent studies suggest that FTO variants strongly correlate with obesity and mainly influence energy intake with little effect on the basal metabolic rate. We suggest that FTO influences eating behavior by modulating intracellular energy levels and downstream signaling mechanisms which control energy intake and metabolism. Since FTO plays a particularly important role in adipocytes and in hypothalamic neurons, SH-SY5Y neuronal cells and 3T3-L1 adipocytes were used to understand how siRNA mediated knockdown of FTO expression alters cellular energy homeostasis. Cellular energy status was evaluated by measuring ATP levels using a luminescence assay and uptake of fluorescent glucose. FTO siRNA in SH-SY5Y cells mediated mRNA knockdown (-82%), increased ATP concentrations by up to 46% (P = 0.013) compared to controls, and decreased phosphorylation of AMPk and Akt in SH SY5Y by -52% and -46% respectively as seen by immunoblotting. In contrast, FTO siRNA in 3T3-L1 cells decreased ATP concentration by -93% (p<0.0005), and increased AMPk and Akt phosphorylation by 204% and 70%, respectively suggesting that FTO mediates control of energy levels in a cell-type specific manner. Furthermore, glucose uptake was decreased in both SH-SY5Y (-51% p = 0.015) and 3T3-L1 cells (-30%, p = 0.0002). We also show that FTO knockdown decreases NPY mRNA expression in SH-SY5Y cells (-21%) through upregulation of pSTAT3 (118%). These results provide important evidence that FTO-variant linked obesity may be associated with altered metabolic functions through activation of downstream metabolic mediators including AMPk. PMID- 22675564 TI - Self-reported health status in primary health care: the influence of immigration and other associated factors. AB - OBJECTIVE: The aims of this study are to compare self-reported health status between Spanish-born and Latin American-born Spanish residents, adjusted by length of residence in the host country; and additionally, to analyse sociodemographic and psychosocial variables associated with a better health status. DESIGN: This is a cross-sectional population based study of Latin American-born (n = 691) and Spanish-born (n = 903) in 15 urban primary health care centres in Madrid (Spain), carried out between 2007 and 2009. The participants provided information, through an interview, about self-reported health status, socioeconomic characteristics, psychosocial factors and migration conditions. Descriptive and multiple logistic regression analyses were conducted. RESULTS: The Spanish-born participants reported a better health status than the Latin America-born participants (79.8% versus 69.3%, p<0.001). Different patterns of self-reported health status were observed depending on the length of residence in the host country. The proportion of immigrants with a better health status is greater in those who have been in Spain for less than five years compared to those who have stayed longer. Better health status is significantly associated with being men, under 34 years old, being Spanish-born, having a monthly incomes of over 1000 euros, and having considerable social support and low stress. CONCLUSIONS: Better self-reported health status is associated with being Spanish born, men, under 34 years old, having an uppermiddle-socioeconomic status, adequate social support, and low stress. Additionally, length of residence in the host country is seen as a related factor in the self-reported health status of immigrants. PMID- 22675563 TI - Developmental exposure to bisphenol A modulates innate but not adaptive immune responses to influenza A virus infection. AB - Bisphenol A (BPA) is used in numerous products, such as plastic bottles and food containers, from which it frequently leaches out and is consumed by humans. There is a growing public concern that BPA exposure may pose a significant threat to human health. Moreover, due to the widespread and constant nature of BPA exposure, not only adults but fetuses and neonates are also exposed to BPA. There is mounting evidence that developmental exposures to chemicals from our environment, including BPA, contribute to diseases late in life; yet, studies of how early life exposures specifically alter the immune system are limited. Herein we report an examination of how maternal exposure to a low, environmentally relevant dose of BPA affects the immune response to infection with influenza A virus. We exposed female mice during pregnancy and through lactation to the oral reference dose for BPA listed by the US Environmental Protection Agency, and comprehensively examined immune parameters directly linked to disease outcomes in adult offspring following infection with influenza A virus. We found that developmental exposure to BPA did not compromise disease-specific adaptive immunity against virus infection, or reduce the host's ability to clear the virus from the infected lung. However, maternal exposure to BPA transiently reduced the extent of infection-associated pulmonary inflammation and anti-viral gene expression in lung tissue. From these observations, we conclude that maternal exposure to BPA slightly modulates innate immunity in adult offspring, but does not impair the anti-viral adaptive immune response, which is critical for virus clearance and survival following influenza virus infection. PMID- 22675565 TI - High accuracy mutation detection in leukemia on a selected panel of cancer genes. AB - With the advent of whole-genome and whole-exome sequencing, high-quality catalogs of recurrently mutated cancer genes are becoming available for many cancer types. Increasing access to sequencing technology, including bench-top sequencers, provide the opportunity to re-sequence a limited set of cancer genes across a patient cohort with limited processing time. Here, we re-sequenced a set of cancer genes in T-cell acute lymphoblastic leukemia (T-ALL) using Nimblegen sequence capture coupled with Roche/454 technology. First, we investigated how a maximal sensitivity and specificity of mutation detection can be achieved through a benchmark study. We tested nine combinations of different mapping and variant calling methods, varied the variant calling parameters, and compared the predicted mutations with a large independent validation set obtained by capillary re-sequencing. We found that the combination of two mapping algorithms, namely BWA-SW and SSAHA2, coupled with the variant calling algorithm Atlas-SNP2 yields the highest sensitivity (95%) and the highest specificity (93%). Next, we applied this analysis pipeline to identify mutations in a set of 58 cancer genes, in a panel of 18 T-ALL cell lines and 15 T-ALL patient samples. We confirmed mutations in known T-ALL drivers, including PHF6, NF1, FBXW7, NOTCH1, KRAS, NRAS, PIK3CA, and PTEN. Interestingly, we also found mutations in several cancer genes that had not been linked to T-ALL before, including JAK3. Finally, we re-sequenced a small set of 39 candidate genes and identified recurrent mutations in TET1, SPRY3 and SPRY4. In conclusion, we established an optimized analysis pipeline for Roche/454 data that can be applied to accurately detect gene mutations in cancer, which led to the identification of several new candidate T-ALL driver mutations. PMID- 22675566 TI - Networked T cell death following macrophage infection by Mycobacterium tuberculosis. AB - BACKGROUND: Depletion of T cells following infection by Mycobacterium tuberculosis (Mtb) impairs disease resolution, and interferes with clinical test performance that relies on cell-mediated immunity. A number of mechanisms contribute to this T cell suppression, such as activation-induced death and trafficking of T cells out of the peripheral circulation and into the diseased lungs. The extent to which Mtb infection of human macrophages affects T cell viability however, is not well characterised. METHODOLOGY/PRINCIPAL FINDINGS: We found that lymphopenia (<1.5 * 10(9) cells/l) was prevalent among culture positive tuberculosis patients, and lymphocyte counts significantly improved post therapy. We previously reported that Mtb-infected human macrophages resulted in death of infected and uninfected bystander macrophages. In the current study, we sought to examine the influence of infected human alveolar macrophages on T cells. We infected primary human alveolar macrophages (the primary host cell for Mtb) or PMA-differentiated THP-1 cells with Mtb H37Ra, then prepared cell-free supernatants. The supernatants of Mtb-infected macrophages caused dose-dependent, caspase-dependent, T cell apoptosis. This toxic effect of infected macrophage secreted factors did not require TNF-alpha or Fas. The supernatant cytotoxic signal(s) were heat-labile and greater than 50 kDa in molecular size. Although ESAT-6 was toxic to T cells, other Mtb-secreted factors tested did not influence T cell viability; nor did macrophage-free Mtb bacilli or broth from Mtb cultures. Furthermore, supernatants from Mycobacterium bovis Bacille de Calmette et Guerin (BCG)- infected macrophages also elicited T cell death suggesting that ESAT-6 itself, although cytotoxic, was not the principal mediator of T cell death in our system. CONCLUSIONS: Mtb-Infected macrophages secrete heat-labile factors that are toxic to T cells, and may contribute to the immunosuppression seen in tuberculosis as well as interfere with microbial eradication in the granuloma. PMID- 22675567 TI - An improved protocol for efficient engraftment in NOD/LTSZ-SCIDIL-2Rgammanull mice allows HIV replication and development of anti-HIV immune responses. AB - Cord blood hematopoietic progenitor cells (CB-HPCs) transplanted immunodeficient NOD/LtsZ-scidIL2Rgamma(null) (NSG) and NOD/SCID/IL2Rgamma(null) (NOG) mice need efficient human cell engraftment for long-term HIV-1 replication studies. Total body irradiation (TBI) is a classical myeloablation regimen used to improve engraftment levels of human cells in these humanized mice. Some recent reports suggest the use of busulfan as a myeloablation regimen to transplant HPCs in neonatal and adult NSG mice. In the present study, we further ameliorated the busulfan myeloablation regimen with fresh CB-CD34+cell transplantation in 3-4 week old NSG mice. In this CB-CD34+transplanted NSG mice engraftment efficiency of human CD45+cell is over 90% in peripheral blood. Optimal engraftment promoted early and increased CD3+T cell levels, with better lymphoid tissue development and prolonged human cell chimerism over 300 days. These humanized NSG mice have shown long-lasting viremia after HIV-1JRCSF and HIV-1Bal inoculation through intravenous and rectal routes. We also saw a gradual decline of the CD4+T cell count, widespread immune activation, up-regulation of inflammation marker and microbial translocation after HIV-1 infection. Humanized NSG mice reconstituted according to our new protocol produced, moderate cellular and humoral immune responses to HIV-1 postinfection. We believe that NSG mice reconstituted according to our easy to use protocol will provide a better in vivo model for HIV 1 replication and anti-HIV-1 therapy trials. PMID- 22675568 TI - Is coarse-to-fine strategy sensitive to normal aging? AB - Theories on visual perception agree that visual recognition begins with global analysis and ends with detailed analysis. Different results from neurophysiological, computational, and behavioral studies all indicate that the totality of visual information is not immediately conveyed, but that information analysis follows a predominantly coarse-to-fine processing sequence (low spatial frequencies are extracted first, followed by high spatial frequencies). We tested whether such processing continues to occur in normally aging subjects. Young and aged participants performed a categorization task (indoor vs. outdoor scenes), using dynamic natural scene stimuli, in which they resorted to either a coarse-to fine (CtF) sequence or a reverse fine-to-coarse sequence (FtC). The results show that young participants categorized CtF sequences more quickly than FtC sequences. However, sequence processing interacts with semantic category only for aged participants. The present data support the notion that CtF categorization is effective even in aged participants, but is constrained by the spatial features of the scenes, thus highlighting new perspectives in visual models. PMID- 22675569 TI - Elimination of specific miRNAs by naked 14-nt sgRNAs. AB - tRNase Z(L)-utilizing efficacious gene silencing (TRUE gene silencing) is a newly developed technology to suppress mammalian gene expression. TRUE gene silencing works on the basis of a unique enzymatic property of mammalian tRNase Z(L), which is that it can recognize a pre-tRNA-like or micro-pre-tRNA-like complex formed between target RNA and artificial small guide RNA (sgRNA) and can cleave any target RNA at any desired site. There are four types of sgRNA, 5'-half-tRNA, RNA heptamer, hook RNA, and ~14-nt linear RNA. Here we show that a 14-nt linear-type sgRNA against human miR-16 can guide tRNase Z(L) cleavage of miR-16 in vitro and can downregulate the miR-16 level in HEK293 cells. We also demonstrate that the 14-nt sgRNA can be efficiently taken up without any transfection reagents by living cells and can exist stably in there for at least 24 hours. The naked 14-nt sgRNA significantly reduced the miR-16 level in HEK293 and HL60 cells. Three other naked 14-nt sgRNAs against miR-142-3p, miR-206, and miR-19a/b are also shown to downregulate the respective miRNA levels in various mammalian cell lines. Our observations suggest that in general we can eliminate a specific cellular miRNA at least by ~50% by using a naked 14-nt sgRNA on the basis of TRUE gene silencing. PMID- 22675570 TI - Unspliced precursors of NMD-sensitive beta-globin transcripts exhibit decreased steady-state levels in erythroid cells. AB - Nonsense-mediated mRNA decay (NMD) is a quality control mechanism that detects and rapidly degrades mRNAs carrying premature translation-termination codons (PTCs). Mammalian NMD depends on both splicing and translation, and requires recognition of the premature stop codon by the cytoplasmic ribosomes. Surprisingly, some published data have suggested that nonsense codons may also affect the nuclear metabolism of the nonsense-mutated transcripts. To determine if nonsense codons could influence nuclear events, we have directly assessed the steady-state levels of the unspliced transcripts of wild-type and PTC-containing human beta-globin genes stably transfected in mouse erythroleukemia (MEL) cells, after erythroid differentiation induction, or in HeLa cells. Our analyses by ribonuclease protection assays and reverse transcription-coupled quantitative PCR show that beta-globin pre-mRNAs carrying NMD-competent PTCs, but not those containing a NMD-resistant PTC, exhibit a significant decrease in their steady state levels relatively to the wild-type or to a missense-mutated beta-globin pre mRNA. On the contrary, in HeLa cells, human beta-globin pre-mRNAs carrying NMD competent PTCs accumulate at normal levels. Functional analyses of these pre mRNAs in MEL cells demonstrate that their low steady-state levels do not reflect significantly lower pre-mRNA stabilities when compared to the normal control. Furthermore, our results also provide evidence that the relative splicing efficiencies of intron 1 and 2 are unaffected. This set of data highlights potential nuclear pathways that might be promoter- and/or cell line-specific, which recognize the NMD-sensitive transcripts as abnormal. These specialized nuclear pathway(s) may be superimposed on the general NMD mechanism. PMID- 22675571 TI - Exploring the impact of language services on utilization and clinical outcomes for diabetics. AB - BACKGROUND: Significant health disparities exist between limited English proficient and English-proficient patients. Little is known about the impact of language services on chronic disease outcomes such as for diabetes. METHODS/PRINCIPAL FINDINGS: To determine whether the amount and type of language services received during primary care visits had an impact on diabetes-related outcomes (hospitalization, emergency room utilization, glycemic control) in limited English proficient patients, a retrospective cohort design was utilized. Hospital and medical record data was examined for 1425 limited English proficient patients in the Cambridge Health Alliance diabetes registry. We categorized patients receiving usual care into 7 groups based on the amount and combination of language services (language concordant providers, formal interpretation and nothing) received at primary care visits during a 9 month period. Bivariate analyses and multiple logistic regression were used to determine relationships between language service categories and outcomes in the subsequent 6 months. Thirty-one percent of patients (445) had no documentation of interpreter use or seeing a language concordant provider in any visits. Patients who received 100% of their primary care visits with language concordant providers were least likely to have diabetes-related emergency department visits compared to other groups (p<0001) in the following 6 months. Patients with higher numbers of co morbidities were more likely to receive formal interpretation. CONCLUSIONS/SIGNIFICANCE: Language concordant providers may help reduce health care utilization for limited English proficient patients with diabetes. However, given the lack of such providers in sufficient numbers to meet patients' communication needs, strategies are needed to both increase their numbers and ensure that the highest risk patients receive the most appropriate language services. In addition, systems serving diverse populations must clarify why some limited English proficient patients do not receive language services at some or all of their visits and whether this has an impact on quality of care. PMID- 22675572 TI - Hepatitis C virus induced a novel apoptosis-like death of pancreatic beta cells through a caspase 3-dependent pathway. AB - Epidemiological and experimental studies have suggested that Hepatitis C virus (HCV) infection is associated with the development of type 2 diabetes. Pancreatic beta cell failure is central to the progression of type 2 diabetes. Using virus infection system, we investigate the influence of HCV infection on the fate of the insulinoma cell line, MIN6. Our experiments demonstrate that the HCV virion itself is indispensable and has a dose- and time-dependent cytopathic effect on the cells. HCV infection inhibits cell proliferation and induces death of MIN6 cells with apoptotic characteristics, including cell surface exposure of phosphatidylserine, decreased mitochondrial membrane potential, activation of caspase 3 and poly (ADP-ribose) polymerase, and DNA fragmentation in the nucleus. However, the fact that HCV-infected cells exhibit a dilated, low-density nucleus with intact plasma and nuclear membrane indicates that a novel apoptosis-like death occurs. HCV infection also causes endoplasmic reticulum (ER) stress. Further, HCV RNA replication was detected in MIN6 cells, although the infection efficiency is very low and no progeny virus particle generates. Taken together, our data suggest that HCV infection induces death of pancreatic beta cells through an ER stress-involved, caspase 3-dependent, special pathway. PMID- 22675574 TI - Accuracy, stability, and corrective behavior in a visuomotor tracking task: a preliminary study. AB - Visuomotor tracking tasks have been used to elucidate the underlying mechanisms that allow for the coordination of a movement to an environmental event. The main purpose of the present study was to examine the relationship between accuracy and stability of tracking performance and the amount of corrective movements that emerge for various coordination patterns in a unimanual visuomotor tracking task. Participants (N = 6) produced rhythmic elbow flexion-extension motions and were required to track an external sinusoidal signal at five different relative phases, 0 degrees , 45 degrees , 90 degrees , 135 degrees , and 180 degrees . Differential accuracy and stability were found among the five tracking patterns with the 0 degrees relative phase pattern being the most accurate and stable pattern. Corrective movements were correlated with changes in accuracy only for the 0 degrees relative phase pattern, with more corrections emerging for less accurate performance. The amount of corrective movements decreased as the stability of tracking performance increased for the 0 degrees , 45 degrees , and 135 degrees patterns. For the 90 degrees and 180 degrees tracking patterns, the amount of corrective movements was not correlated with pattern accuracy or pattern stability. The results demonstrate that corrective behaviors are an important motor process in maintaining the stability of stable perception-action coordination patterns, while offering little benefit for unstable perception action patterns. PMID- 22675573 TI - A simplified, sensitive phagocytic assay for malaria cultures facilitated by flow cytometry of differentially-stained cell populations. AB - BACKGROUND: Phagocytosis of infected and uninfected erythrocytes is an important feature of malaria infections. Flow cytometry is a useful tool for studying phagocytic uptake of malaria-infected erythrocytes in vitro. However, current approaches are limited by the inability to discriminate between infected and uninfected erythrocytes and a failure to stain the early developmental ring stages of infected erythrocytes. The majority of infected erythrocytes in circulation are of the ring stage and these are therefore important targets to study. METHODOLOGY/PRINCIPAL FINDINGS: In vitro P. falciparum cultures comprising infected and uninfected erythrocytes were labeled and exposed to cells derived from the human monocytic THP-1 cell line. Phagocytosis was assayed by flow cytometry. Dual labeling of Plasmodium DNA and erythrocyte cytoplasm with dihydroethidium and CellTraceTM Violet respectively allowed, for the first time, the detection and enumeration of phagocytes with ingested erythrocytes from both early ring- and late schizont-stage P, falciparum cultures. The sensitivity of the method was tested using varying conditions including phagocyte type (monocytes versus macrophages), parasite stage (rings versus schizonts), and negative (incubation with cytochalasin D) and positive (incubation with immune sera) effectors of phagocytosis. The current assay clearly demonstrated uptake of infected and uninfected erythrocytes exposed to phagocytes; the extent of which was dependent on the conditions mentioned. CONCLUSIONS: We describe a simple, sensitive and rapid method for quantifying phagocytosis of P. falciparum-infected erythrocytes, by flow cytometry. This approach can be applied for studying parasite-phagocyte interactions under a variety of conditions. The investigation of phagocytosis of P. falciparum-infected erythrocytes can extend from looking solely at late-staged infected erythrocytes to include early-staged ones as well. It does away with the need to purify infected cells, allowing the study of effects on neighboring uninfected cells. This method may also be translated for use with different types of phagocytes. PMID- 22675575 TI - Caution in interpreting results from imputation analysis when linkage disequilibrium extends over a large distance: a case study on venous thrombosis. AB - By applying an imputation strategy based on the 1000 Genomes project to two genome-wide association studies (GWAS), we detected a susceptibility locus for venous thrombosis on chromosome 11p11.2 that was missed by previous GWAS analyses that had been conducted on the same datasets. A comprehensive linkage disequilibrium and haplotype analysis of the whole locus where twelve SNPs exhibited association p-values lower than 2.23 10(-11) and the use of independent case-control samples demonstrated that the culprit variant was a rare variant located ~1 Mb away from the original hits, not tagged by current genome-wide genotyping arrays and even not well imputed in the original GWAS samples. This variant was in fact the rs1799963, also known as the FII G20210A prothrombin mutation. This work may be of major interest not only for its scientific impact but also for its methodological findings. PMID- 22675577 TI - The state of standards in genomic sciences. PMID- 22675576 TI - LSK derived LSK- cells have a high apoptotic rate related to survival regulation of hematopoietic and leukemic stem cells. AB - A balanced pool of hematopoietic stem cells (HSCs) in bone marrow is tightly regulated, and this regulation is disturbed in hematopoietic malignancies such as chronic myeloid leukemia (CML). The underlying mechanisms are largely unknown. Here we show that the Lin(-)Sca-1(+)c-Kit(-) (LSK(-)) cell population derived from HSC-containing Lin(-)Sca-1(+)c-Kit(+) (LSK) cells has significantly higher numbers of apoptotic cells. Depletion of LSK cells by radiation or the cytotoxic chemical 5-fluorouracil results in an expansion of the LSK(-) population. In contrast, the LSK(-) population is reduced in CML mice, and depletion of leukemia stem cells (LSCs; BCR-ABL-expressing HSCs) by deleting Alox5 or by inhibiting heat shock protein 90 causes an increase in this LSK(-) population. The transition of LSK to LSK(-) cells is controlled by the Icsbp gene and its downstream gene Lyn, and regulation of this cellular transition is critical for the survival of normal LSK cells and LSCs. These results indicate a potential function of the LSK(-) cells in the regulation of LSK cells and LSCs. PMID- 22675578 TI - Draft genome sequence of strain HIMB100, a cultured representative of the SAR116 clade of marine Alphaproteobacteria. AB - Strain HIMB100 is a planktonic marine bacterium in the class Alphaproteobacteria. This strain is of interest because it is one of the first known isolates from a globally ubiquitous clade of marine bacteria known as SAR116 within the family Rhodospirillaceae. Here we describe preliminary features of the organism, together with the draft genome sequence and annotation. This is the second genome sequence of a member of the SAR116 clade. The 2,458,945 bp genome contains 2,334 protein-coding and 42 RNA genes. PMID- 22675579 TI - Complete genome of the onion pathogen Enterobacter cloacae EcWSU1. PMID- 22675580 TI - Complete genome sequence of Hirschia baltica type strain (IFAM 1418(T)). AB - The family Hyphomonadaceae within the Alphaproteobacteria is largely comprised of bacteria isolated from marine environments with striking morphologies and an unusual mode of cell growth. Here, we report the complete genome sequence Hirschia baltica, which is only the second a member of the Hyphomonadaceae with a published genome sequence. H. baltica is of special interest because it has a dimorphic life cycle and is a stalked, budding bacterium. The 3,455,622 bp long chromosome and 84,492 bp plasmid with a total of 3,222 protein-coding and 44 RNA genes were sequenced as part of the DOE Joint Genome Institute Program CSP 2008. PMID- 22675581 TI - Complete genome sequence of Parvibaculum lavamentivorans type strain (DS-1(T)). AB - Parvibaculum lavamentivorans DS-1(T) is the type species of the novel genus Parvibaculum in the novel family Rhodobiaceae (formerly Phyllobacteriaceae) of the order Rhizobiales of Alphaproteobacteria. Strain DS-1(T) is a non-pigmented, aerobic, heterotrophic bacterium and represents the first tier member of environmentally important bacterial communities that catalyze the complete degradation of synthetic laundry surfactants. Here we describe the features of this organism, together with the complete genome sequence and annotation. The 3,914,745 bp long genome with its predicted 3,654 protein coding genes is the first completed genome sequence of the genus Parvibaculum, and the first genome sequence of a representative of the family Rhodobiaceae. PMID- 22675583 TI - Complete Genome Sequence of a thermotolerant sporogenic lactic acid bacterium, Bacillus coagulans strain 36D1. AB - Bacillus coagulans is a ubiquitous soil bacterium that grows at 50-55 degrees C and pH 5.0 and ferments various sugars that constitute plant biomass to L (+) lactic acid. The ability of this sporogenic lactic acid bacterium to grow at 50 55 degrees C and pH 5.0 makes this organism an attractive microbial biocatalyst for production of optically pure lactic acid at industrial scale not only from glucose derived from cellulose but also from xylose, a major constituent of hemicellulose. This bacterium is also considered as a potential probiotic. Complete genome sequence of a representative strain, B. coagulans strain 36D1, is presented and discussed. PMID- 22675582 TI - Complete genome sequence of Allochromatium vinosum DSM 180(T). AB - Allochromatium vinosum formerly Chromatium vinosum is a mesophilic purple sulfur bacterium belonging to the family Chromatiaceae in the bacterial class Gammaproteobacteria. The genus Allochromatium contains currently five species. All members were isolated from freshwater, brackish water or marine habitats and are predominately obligate phototrophs. Here we describe the features of the organism, together with the complete genome sequence and annotation. This is the first completed genome sequence of a member of the Chromatiaceae within the purple sulfur bacteria thriving in globally occurring habitats. The 3,669,074 bp genome with its 3,302 protein-coding and 64 RNA genes was sequenced within the Joint Genome Institute Community Sequencing Program. PMID- 22675584 TI - Complete genome sequence of Thioalkalivibrio sp. K90mix. AB - Thioalkalivibrio sp. K90mix is an obligately chemolithoautotrophic, natronophilic sulfur-oxidizing bacterium (SOxB) belonging to the family Ectothiorhodospiraceae within the Gammaproteobacteria. The strain was isolated from a mixture of sediment samples obtained from different soda lakes located in the Kulunda Steppe (Altai, Russia) based on its extreme potassium carbonate tolerance as an enrichment method. Here we report the complete genome sequence of strain K90mix and its annotation. The genome was sequenced within the Joint Genome Institute Community Sequencing Program, because of its relevance to the sustainable removal of sulfide from wastewater and gas streams. PMID- 22675585 TI - Complete genome sequence of the filamentous gliding predatory bacterium Herpetosiphon aurantiacus type strain (114-95(T)). AB - Herpetosiphon aurantiacus Holt and Lewin 1968 is the type species of the genus Herpetosiphon, which in turn is the type genus of the family Herpetosiphonaceae, type family of the order Herpetosiphonales in the phylum Chloroflexi. H. aurantiacus cells are organized in filaments which can rapidly glide. The species is of interest not only because of its rather isolated position in the tree of life, but also because Herpetosiphon ssp. were identified as predators capable of facultative predation by a wolf pack strategy and of degrading the prey organisms by excreted hydrolytic enzymes. The genome of H. aurantiacus strain 114-95(T) is the first completely sequenced genome of a member of the family Herpetosiphonaceae. The 6,346,587 bp long chromosome and the two 339,639 bp and 99,204 bp long plasmids with a total of 5,577 protein-coding and 77 RNA genes was sequenced as part of the DOE Joint Genome Institute Program DOEM 2005. PMID- 22675586 TI - Complete genome sequence of Desulfurispirillum indicum strain S5(T). AB - Desulfurispirillum indicum strain S5(T) is a strictly anaerobic bacterium isolated from river sediment in Chennai, India. D. indicum belongs to the deep branching phylum of Chrysiogenetes, which currently only includes three other cultured species. Strain S5(T) is the type strain of the species and it is capable of growth using selenate, selenite, arsenate, nitrate or nitrite as terminal electron acceptors. The 2,928,377 bp genome encodes 2,619 proteins and 49 RNA genes, and the information gained from its sequence will be relevant to the elucidation of microbially-mediated transformations of arsenic and selenium, in addition to deepening our knowledge of the underrepresented phylum of Chrysiogenetes. PMID- 22675587 TI - Complete genome sequence of the halophilic and highly halotolerant Chromohalobacter salexigens type strain (1H11(T)). AB - Chromohalobacter salexigens is one of nine currently known species of the genus Chromohalobacter in the family Halomonadaceae. It is the most halotolerant of the so-called 'moderately halophilic bacteria' currently known and, due to its strong euryhaline phenotype, it is an established model organism for prokaryotic osmoadaptation. C. salexigens strain 1H11(T) and Halomonas elongata are the first and the second members of the family Halomonadaceae with a completely sequenced genome. The 3,696,649 bp long chromosome with a total of 3,319 protein-coding and 93 RNA genes was sequenced as part of the DOE Joint Genome Institute Program DOEM 2004. PMID- 22675588 TI - High quality draft genome sequence of Segniliparus rugosus CDC 945(T)= (ATCC BAA 974(T)). AB - Segniliparus rugosus represents one of two species in the genus Segniliparus, the sole genus in the family Segniliparaceae. A unique and interesting feature of this family is the presence of extremely long carbon-chain length mycolic acids bound in the cell wall. S. rugosus is also a medically important species because it is an opportunistic pathogen associated with mammalian lung disease. This report represents the second species in the genus to have its genome sequenced. The 3,567,567 bp long genome with 3,516 protein-coding and 49 RNA genes is part of the NIH Roadmap for Medical Research, Human Microbiome Project. PMID- 22675589 TI - Genome sequence of the filamentous, gliding Thiothrix nivea neotype strain (JP2(T)). AB - Thiothrix nivea (Rabenhorst 1865) Winogradsky 1888 (Approved Lists 1980) emend. Larkin and Shinabarger 1983 is the type species of the genus Thiothrix in the family Thiotrichaceae. The species is of interest not only because of its isolated location in the yet to be genomically characterized region of the tree of life, but also because of its life-style with gliding gonidia, the multilayer sheath, rosettes, and the embedded sulfur granules. Strain JP2(T) is the neotype strain of the species which was first observed by Rabenhorst in 1865 and later reclassified by Winogradsky in 1888 into the then novel genus Thiothrix. This is the first completed (improved-high-quality-draft) genome sequence to be published of a member of the family Thiotrichaceae. The genome in its current assembly consists of 15 contigs in four scaffolds with a total of 4,691,711 bp bearing 4,542 protein-coding and 52 RNA genes and is a part of the Genomic Encyclopedia of Bacteria and Archaea project. PMID- 22675591 TI - SOP for pathway inference in Integrated Microbial Genomes (IMG). AB - One of the most important aspects of genomic analysis is the prediction of which pathways, both metabolic and non-metabolic, are present in an organism. In IMG, this is carried out by the assignment of IMG terms, which are organized into IMG pathways. Based on manual and automatic assignment of IMG terms, the presence or absence of IMG pathways is automatically inferred. The three categories of pathway assertion are asserted (likely present), not asserted (likely absent), and unknown. In the unknown category, at least one term necessary for the pathway is missing, but an ortholog in another organism has the corresponding term assigned to it. Automatic pathway inference is an important initial step in genome analysis. PMID- 22675590 TI - Complete genome sequence of the thermophilic sulfur-reducer Desulfurobacterium thermolithotrophum type strain (BSA(T)) from a deep-sea hydrothermal vent. AB - Desulfurobacterium thermolithotrophum L'Haridon et al. 1998 is the type species of the genus Desulfurobacterium which belongs to the family Desulfurobacteriaceae. The species is of interest because it represents the first thermophilic bacterium that can act as a primary producer in the temperature range of 45-75 degrees C (optimum 70 degrees C) and is incapable of growing under microaerophilic conditions. Strain BSA(T) preferentially synthesizes high melting-point fatty acids (C(18) and C(20)) which is hypothesized to be a strategy to ensure the functionality of the membrane at high growth temperatures. This is the second completed genome sequence of a member of the family Desulfurobacteriaceae and the first sequence from the genus Desulfurobacterium. The 1,541,968 bp long genome harbors 1,543 protein-coding and 51 RNA genes and is a part of the Genomic Encyclopedia of Bacteria and Archaea project. PMID- 22675592 TI - The pathway tools pathway prediction algorithm. AB - The PathoLogic component of the Pathway Tools software performs prediction of metabolic pathways in sequenced and annotated genomes. This article provides a detailed presentation of the PathoLogic algorithm. The algorithm consists of two phases. The reactome inference phase infers the reactions catalyzed by the organism from the set of enzymes present in the annotated genome. The pathway inference phase infers the metabolic pathways present in the organism from the reactions catalyzed by the organism. Both phases draw on the MetaCyc database of metabolic reactions and pathways. MetaCyc contains two data fields to support pathway inference: the expected taxonomic range of each pathway, and a list of key reactions for pathways. These fields have significantly increased the predictive accuracy of PathoLogic. PMID- 22675593 TI - Complete genome sequence of Paenibacillus sp. strain JDR-2. AB - Paenibacillus sp. strain JDR-2, an aggressively xylanolytic bacterium isolated from sweetgum (Liquidambar styraciflua) wood, is able to efficiently depolymerize, assimilate and metabolize 4-O-methylglucuronoxylan, the predominant structural component of hardwood hemicelluloses. A basis for this capability was first supported by the identification of genes and characterization of encoded enzymes and has been further defined by the sequencing and annotation of the complete genome, which we describe. In addition to genes implicated in the utilization of beta-1,4-xylan, genes have also been identified for the utilization of other hemicellulosic polysaccharides. The genome of Paenibacillus sp. JDR-2 contains 7,184,930 bp in a single replicon with 6,288 protein-coding and 122 RNA genes. Uniquely prominent are 874 genes encoding proteins involved in carbohydrate transport and metabolism. The prevalence and organization of these genes support a metabolic potential for bioprocessing of hemicellulose fractions derived from lignocellulosic resources. PMID- 22675594 TI - Genome sequence of strain HIMB624, a cultured representative from the OM43 clade of marine Betaproteobacteria. PMID- 22675595 TI - Complete genome sequence of the aerobic, heterotroph Marinithermus hydrothermalis type strain (T1(T)) from a deep-sea hydrothermal vent chimney. AB - Marinithermus hydrothermalis Sako et al. 2003 is the type species of the monotypic genus Marinithermus. M. hydrothermalis T1(T) was the first isolate within the phylum "Thermus-Deinococcus" to exhibit optimal growth under a salinity equivalent to that of sea water and to have an absolute requirement for NaCl for growth. M. hydrothermalis T1(T) is of interest because it may provide a new insight into the ecological significance of the aerobic, thermophilic decomposers in the circulation of organic compounds in deep-sea hydrothermal vent ecosystems. This is the first completed genome sequence of a member of the genus Marinithermus and the seventh sequence from the family Thermaceae. Here we describe the features of this organism, together with the complete genome sequence and annotation. The 2,269,167 bp long genome with its 2,251 protein coding and 59 RNA genes is a part of the Genomic Encyclopedia of Bacteria and Archaea project. PMID- 22675596 TI - Complete genome sequence of Halopiger xanaduensis type strain (SH-6(T)). AB - Halopiger xanaduensis is the type species of the genus Halopiger and belongs to the euryarchaeal family Halobacteriaceae. H. xanaduensis strain SH-6, which is designated as the type strain, was isolated from the sediment of a salt lake in Inner Mongolia, Lake Shangmatala. Like other members of the family Halobacteriaceae, it is an extreme halophile requiring at least 2.5 M salt for growth. We report here the sequencing and annotation of the 4,355,268 bp genome, which includes one chromosome and three plasmids. This genome is part of a Joint Genome Institute (JGI) Community Sequencing Program (CSP) project to sequence diverse haloarchaeal genomes. PMID- 22675597 TI - Draft genome sequence of Arthrospira platensis C1 (PCC9438). AB - Arthrospira platensis is a cyanobacterium that is extensively cultivated outdoors on a large commercial scale for consumption as a food for humans and animals. It can be grown in monoculture under highly alkaline conditions, making it attractive for industrial production. Here we describe the complete genome sequence of A. platensis C1 strain and its annotation. The A. platensis C1 genome contains 6,089,210 bp including 6,108 protein-coding genes and 45 RNA genes, and no plasmids. The genome information has been used for further comparative analysis, particularly of metabolic pathways, photosynthetic efficiency and barriers to gene transfer. PMID- 22675598 TI - Complete genome sequence of the rapeseed plant-growth promoting Serratia plymuthica strain AS9. AB - Serratia plymuthica are plant-associated, plant beneficial species belonging to the family Enterobacteriaceae. The members of the genus Serratia are ubiquitous in nature and their life style varies from endophytic to free-living. S. plymuthica AS9 is of special interest for its ability to inhibit fungal pathogens of rapeseed and to promote plant growth. The genome of S. plymuthica AS9 comprises a 5,442,880 bp long circular chromosome that consists of 4,952 protein coding genes, 87 tRNA genes and 7 rRNA operons. This genome is part of the project entitled "Genomics of four rapeseed plant growth promoting bacteria with antagonistic effect on plant pathogens" awarded through the 2010 DOE-JGI Community Sequencing Program (CSP2010). PMID- 22675599 TI - Complete genome sequence of the melanogenic marine bacterium Marinomonas mediterranea type strain (MMB-1(T)). AB - Marinomonas mediterranea MMB-1(T) Solano & Sanchez-Amat 1999 belongs to the family Oceanospirillaceae within the phylum Proteobacteria. This species is of interest because it is the only species described in the genus Marinomonas to date that can synthesize melanin pigments, which is mediated by the activity of a tyrosinase. M. mediterranea expresses other oxidases of biotechnological interest, such as a multicopper oxidase with laccase activity and a novel L lysine-epsilon-oxidase. The 4,684,316 bp long genome harbors 4,228 protein-coding genes and 98 RNA genes and is a part of the Genomic Encyclopedia of Bacteria and Archaea project. PMID- 22675600 TI - Complete genome sequence of Polynucleobacter necessarius subsp. asymbioticus type strain (QLW-P1DMWA-1(T)). AB - Polynucleobacter necessarius subsp. asymbioticus strain QLW-P1DMWA-1(T) is a planktonic freshwater bacterium affiliated with the family Burkholderiaceae (class Betaproteobacteria). This strain is of interest because it represents a subspecies with cosmopolitan and ubiquitous distribution in standing freshwater systems. The 16S-23S ITS genotype represented by the sequenced strain comprised on average more than 10% of bacterioplankton in its home habitat. While all strains of the subspecies P. necessarius asymbioticus are free-living freshwater bacteria, strains belonging to the only other subspecies, P. necessarius subsp. necessarius are obligate endosymbionts of the ciliate Euplotes aediculatus. The two subspecies of P. necessarius are the instances of two closely related subspecies that differ in their lifestyle (free-living vs. obligate endosymbiont), and they are the only members of the genus Polynucleobacter with completely sequenced genomes. Here we describe the features of P. necessarius subsp. asymbioticus, together with the complete genome sequence and annotation. The 2,159,490 bp long chromosome with a total of 2,088 protein-coding and 48 RNA genes is the first completed genome sequence of the genus Polynucleobacter to be published and was sequenced as part of the DOE Joint Genome Institute Community Sequencing Program 2006. PMID- 22675601 TI - Complete genome sequencing and analysis of Saprospira grandis str. Lewin, a predatory marine bacterium. AB - Saprospira grandis is a coastal marine bacterium that can capture and prey upon other marine bacteria using a mechanism known as 'ixotrophy'. Here, we present the complete genome sequence of Saprospira grandis str. Lewin isolated from La Jolla beach in San Diego, California. The complete genome sequence comprises a chromosome of 4.35 Mbp and a plasmid of 54.9 Kbp. Genome analysis revealed incomplete pathways for the biosynthesis of nine essential amino acids but presence of a large number of peptidases. The genome encodes multiple copies of sensor globin-coupled rsbR genes thought to be essential for stress response and the presence of such sensor globins in Bacteroidetes is unprecedented. A total of 429 spacer sequences within the three CRISPR repeat regions were identified in the genome and this number is the largest among all the Bacteroidetes sequenced to date. PMID- 22675602 TI - Complete genome sequence of the sulfur compounds oxidizing chemolithoautotroph Sulfuricurvum kujiense type strain (YK-1(T)). AB - Sulfuricurvum kujiense Kodama and Watanabe 2004 is the type species of the monotypic genus Sulfuricurvum, which belongs to the family Helicobacteraceae in the class Epsilonproteobacteria. The species is of interest because it is frequently found in crude oil and oil sands where it utilizes various reduced sulfur compounds such as elemental sulfur, sulfide and thiosulfate as electron donors. Members of the species do not utilize sugars, organic acids or hydrocarbons as carbon and energy sources. This genome sequence represents the type strain of the only species in the genus Sulfuricurvum. The genome, which consists of a circular chromosome of 2,574,824 bp length and four plasmids of 118,585 bp, 71,513 bp, 51,014 bp, and 3,421 bp length, respectively, harboring a total of 2,879 protein-coding and 61 RNA genes and is a part of the Genomic Encyclopedia of Bacteria and Archaea project. PMID- 22675603 TI - Complete Genome Sequence of Clostridium clariflavum DSM 19732. AB - Clostridium clariflavum is a Cluster III Clostridium within the family Clostridiaceae isolated from thermophilic anaerobic sludge (Shiratori et al, 2009). This species is of interest because of its similarity to the model cellulolytic organism Clostridium thermocellum and for the ability of environmental isolates to break down cellulose and hemicellulose. Here we describe features of the 4,897,678 bp long genome and its annotation, consisting of 4,131 protein-coding and 98 RNA genes, for the type strain DSM 19732. PMID- 22675604 TI - Non-contiguous finished genome sequence and description of Anaerococcus senegalensis sp. nov. PMID- 22675605 TI - Conceptualizing a Genomics Software Institute (GSI). AB - Microbial ecology has been enhanced greatly by the ongoing 'omics revolution, bringing half the world's biomass and most of its biodiversity into analytical view for the first time; indeed, it feels almost like the invention of the microscope and the discovery of the new world at the same time. With major microbial ecology research efforts accumulating prodigious quantities of sequence, protein, and metabolite data, we are now poised to address environmental microbial research at macro scales, and to begin to characterize and understand the dimensions of microbial biodiversity on the planet. What is currently impeding progress is the need for a framework within which the research community can develop, exchange and discuss predictive ecosystem models that describe the biodiversity and functional interactions. Such a framework must encompass data and metadata transparency and interoperation; data and results validation, curation, and search; application programming interfaces for modeling and analysis tools; and human and technical processes and services necessary to ensure broad adoption. Here we discuss the need for focused community interaction to augment and deepen established community efforts, beginning with the Genomic Standards Consortium (GSC), to create a science-driven strategic plan for a Genomic Software Institute (GSI). PMID- 22675606 TI - Differential regulation of protein synthesis in skeletal muscle and liver of neonatal pigs by leucine through an mTORC1-dependent pathway. AB - Neonatal growth is characterized by a high protein synthesis rate that is largely due to an enhanced sensitivity to the postprandial rise in insulin and amino acids, especially leucine. The mechanism of leucine's action in vivo is not well understood. In this study, we investigated the effect of leucine infusion on protein synthesis in skeletal muscle and liver of neonatal pigs. To evaluate the mode of action of leucine, we used rapamycin, an inhibitor of mammalian target of rapamycin (mTOR) complex-1 (mTORC1). Overnight-fasted 7-day-old piglets were treated with rapamycin for 1 hour and then infused with leucine (400 MUmol.kg( 1).h(-1)) for 1 hour. Leucine infusion increased the rate of protein synthesis, and ribosomal protein S6 kinase 1 (S6K1) and eukaryotic initiation factor (eIF) 4E-binding protein-1 (4E-BP1) phosphorylation in gastrocnemius and masseter muscles (P < 0.05), but not in the liver. The leucine-induced stimulation of protein synthesis and S6K1 and 4E-BP1 phosphorylation were completely blocked by rapamycin, suggesting that leucine action is by an mTORC1-dependent mechanism. Neither leucine nor rapamycin had any effect on the activation of the upstream mTORC1 regulators, AMP-activated protein kinase and protein kinase B, in skeletal muscle or liver. The activation of eIF2alpha and elongation factor 2 was not affected by leucine or rapamycin, indicating that these two pathways are not limiting steps of leucine-induced protein synthesis. These results suggest that leucine stimulates muscle protein synthesis in neonatal pigs by inducing the activation of mTORC1 and its downstream pathway leading to mRNA translation. PMID- 22675607 TI - On the hydration state of amino acids and their derivatives at different ionization States: a comparative multinuclear NMR and crystallographic investigation. AB - (2)D, (13)C, (14)N, and (17)O NMR and crystallographic data from the literature were critically evaluated in order to provide a coherent hydration model of amino acids and selected derivatives at different ionization states. (17)O shielding variations, longitudinal relaxation times (T(1)) of (2)D and (13)C and line widths (Deltanu(1/2)) of (14)N and (17)O, may be interpreted with the hypothesis that the cationic form of amino acids is more hydrated by 1 to 3 molecules of water than the zwitterionic form. Similar behaviour was also observed for N acetylated derivatives of amino acids. An exhaustive search in crystal structure databases demonstrates the importance of six-membered hydrogen-bonded conjugated rings of both oxygens of the alpha-carboxylate group with a molecule of water in the vicinity. This type of hydrogen bond mode is absent in the case of the carboxylic groups. Moreover, a considerable number of structures was identified with the propensity to form intramolecular hydrogen bond both in the carboxylic acid (NH?O=C) and in the carboxylate (NH ? O(-)) ionization state. In the presence of bound molecules of water this interaction is significantly reduced in the case of the carboxylate group whereas it is statistically negligible in the carboxylic group. PMID- 22675608 TI - Ambulatory arterial stiffness index is higher in hypertensive patients with chronic kidney disease. AB - Ambulatory arterial stiffness index (AASI) is a parameter obtained from ambulatory blood pressure monitoring (ABPM) that correlates with clinical endpoints. The aim of this study was to compare AASI in nondiabetic hypertensive patients with and without chronic kidney disease (CKD). Subjects with systemic arterial hypertension (SAH, n = 30) with normal renal function, aged 40 to 75 years, were compared to hypertensive patients with CKD (n = 30) presenting estimated glomerular filtration rate (eGFR) <60 mL/min by MDRD formula. ABPM was carried out in all patients. In CKD group, eGFR was 35.3 +/- 2.8 ml/min. The mean 24-hour systolic and diastolic blood pressure (BP) was similar in both groups. AASI was significantly higher in CKD group (0.45 +/- 0.03 versus 0.37 +/- 0.02, P < 0.05), positively correlated to age (r = 0.38, P < 0.01) and pulse pressure (r = 0.43, P < 0.01) and negatively correlated to nocturnal BP fall (r = -0.28, P = 0.03). These findings indicate the presence of stiffer vessels in CKD hypertensive patients. PMID- 22675609 TI - Pharmacologic treatment of obesity. PMID- 22675611 TI - Impact of the -174 G > C IL-6 polymorphism on bioelectrical parameters in obese subjects after laparoscopic adjustable gastric banding. AB - BACKGROUND: Recent data demonstrated that the -174 G > C IL-6 polymorphism may account for differences in the therapeutic response to laparoscopic adjustable gastric banding (LAGB) surgery. OBJECTIVE: We investigated the impact of -174 G > C IL-6 polymorphism on weight loss, body composition, and fluid distribution changes in obese subjects after LAGB. DESIGN AND OUTCOME MEASURES: Twenty obese subjects were selected and studied at baseline and 3 months after LAGB. Genetic assessment of -174 G > C IL-6 polymorphism and anthropometric and bioelectrical impedance analysis were performed. RESULTS: At baseline, C(+) carriers had a lower extracellular water (ECW) and higher intra-CW, phase angle (PA), reactance X(c), and X(c)/height. LAGB surgery determined significant reductions in weight and BMI. After LAGB, in C(-) carriers, significant decreases in weight, BMI, and ECW and increases in BCM, BCMI, ICW, PA, and X(c)/H were highlighted. In C(+) carriers, significant reductions in weight, BMI, ICW, and PA and increases in ECW, Na/K, resistance (R), and R/height were obtained. Significant higher reductions in BMI and X(c)/H were observed in C(+) with respect to C(-) carriers. CONCLUSIONS: Genotyping of genetic variants, for example, the -174 G > C polymorphism of IL-6, gives the opportunity to predict therapeutic response, in terms of body composition outcomes after LAGB. PMID- 22675610 TI - Need for early interventions in the prevention of pediatric overweight: a review and upcoming directions. AB - Childhood obesity is currently one of the most prevailing and challenging public health issues among industrialized countries and of international priority. The global prevalence of obesity poses such a serious concern that the World Health Organization (WHO) has described it as a "global epidemic." Recent literature suggests that the genesis of the problem occurs in the first years of life as feeding patterns, dietary habits, and parental feeding practices are established. Obesity prevention evidence points to specific dietary factors, such as the promotion of breastfeeding and appropriate introduction of nutritious complementary foods, but also calls for attention to parental feeding practices, awareness of appropriate responses to infant hunger and satiety cues, physical activity/inactivity behaviors, infant sleep duration, and family meals. Interventions that begin at birth, targeting multiple factors related to healthy growth, have not been adequately studied. Due to the overwhelming importance and global significance of excess weight within pediatric populations, this narrative review was undertaken to summarize factors associated with overweight and obesity among infants and toddlers, with focus on potentially modifiable risk factors beginning at birth, and to address the need for early intervention prevention. PMID- 22675612 TI - Longitudinal associations of leisure-time physical activity and cancer mortality in the Third National Health and Nutrition Examination Survey (1986-2006). AB - Longitudinal associations between leisure-time physical activity (LTPA) and overall cancer mortality were evaluated within the Third National Health and Nutrition Examination Survey (NHANES III; 1988-2006; n = 15,535). Mortality status was ascertained using the National Death Index. Self-reported LTPA was divided into inactive, regular low-to-moderate and vigorous activity. A frequency weighted metabolic equivalents (METS/week) variable was also computed. Hazard ratios (HRs) and 95% confidence intervals (CI) were calculated for overall cancer mortality in the whole sample, by body mass index categories and insulin resistance (IR) status. Nonsignificant protective associations were observed for regular low-to-moderate and vigorous activity, and for the highest quartile of METS/week (HRs range: 0.66-0.95). Individuals without IR engaging in regular vigorous activity had a 48% decreased risk of cancer mortality (HR: 0.52; 95% CI: 0.28-0.98) in multivariate analyses. Conversely, nonsignificant positive associations were observed in people with IR. In conclusion, regular vigorous activity may reduce risk of cancer mortality among persons with normal insulin glucose metabolism in this national sample. PMID- 22675613 TI - Differences in lipid measurements by antiretroviral regimen exposure in cohorts from Asia and australia. AB - We explored the mean differences in routinely measured lipids (total cholesterol, triglycerides, and high-density lipoprotein cholesterol) according to exposure to different combination antiretroviral regimens in Asian (n = 2051) and Australian (predominantly Caucasian, n = 794) cohorts. The regimen was defined as at least 3 antiretroviral drugs with at least 2 nucleoside-reverse transcriptases (NRTIs) and either of at least one protease inhibitor (PI) or non-nucleoside-reverse transcriptases (NNRTIs). We categorised cART regimens as: NRTIs as tenofovir based or not; NNRTIs as nevirapine or efavirenz (but not both); and PI as atazanavir based or not. We found that the impact of various antiretroviral regimens on lipids in Asian and Australian cohorts was only different by cohort for total cholesterol (P for interaction between regimen and cohort: <0.001) but not in case of other lipids (P for interaction: >0.05). The differences in total cholesterol were however small and unlikely to be of clinical significance. Overall, tenofovir with nevirapine or atazanavir was associated with the most favorable lipids, while the PI regimens without tenofovir and atazanavir were associated with least favorable lipids. We conclude that the impact of various ART regimens on lipids is largely similar in Asian and Australian cohorts and that the newer drugs such as tenofovir and atazanavir are likely to provide similar benefit in terms of lipid profiles in both populations. PMID- 22675614 TI - Elevated circulating angiogenic progenitors and white blood cells are associated with hypoxia-inducible angiogenic growth factors in children with sickle cell disease. AB - We studied the number and function of angiogenic progenitor cells and growth factors in children aged 5-18 years without acute illness, 43 with Hemoglobin SS and 68 with normal hemoglobin. Hemoglobin SS subjects had at least twice as many mononuclear cell colonies and more circulating progenitor cell than Control subjects. Plasma concentrations of erythropoietin, angiopoietin-2, and stromal derived growth factor (SDF)-1alpha were significantly higher in children with Hemoglobin SS compared to Control subjects. In a multivariate analysis model, SDF 1alpha concentration was found to be associated with both CPC number and total white blood cell count in the Hemoglobin SS group, suggesting that SDF-1alpha produced by ischemic tissues plays a role in mobilizing these cells in children with Hemoglobin SS. Despite having a higher number of angiogenic progenitor cells, children with Hemoglobin SS had slower migration of cultured mononuclear cells. PMID- 22675616 TI - Chromosomal aberrations associated with clonal evolution and leukemic transformation in fanconi anemia: clinical and biological implications. AB - Fanconi anaemia (FA) is an inherited disease with congenital and developmental abnormalities, bone marrow failure, and extreme risk of leukemic transformation. Bone marrow surveillance is an important part of the clinical management of FA and often reveals cytogenetic aberrations. Here, we review bone marrow findings in FA and discuss the clinical and biological implications of chromosomal aberrations associated with leukemic transformation. PMID- 22675615 TI - Disrupted Signaling through the Fanconi Anemia Pathway Leads to Dysfunctional Hematopoietic Stem Cell Biology: Underlying Mechanisms and Potential Therapeutic Strategies. AB - Fanconi anemia (FA) is the most common inherited bone marrow failure syndrome. FA patients suffer to varying degrees from a heterogeneous range of developmental defects and, in addition, have an increased likelihood of developing cancer. Almost all FA patients develop a severe, progressive bone marrow failure syndrome, which impacts upon the production of all hematopoietic lineages and, hence, is thought to be driven by a defect at the level of the hematopoietic stem cell (HSC). This hypothesis would also correlate with the very high incidence of MDS and AML that is observed in FA patients. In this paper, we discuss the evidence that supports the role of dysfunctional HSC biology in driving the etiology of the disease. Furthermore, we consider the different model systems currently available to study the biology of cells defective in the FA signaling pathway and how they are informative in terms of identifying the physiologic mediators of HSC depletion and dissecting their putative mechanism of action. Finally, we ask whether the insights gained using such disease models can be translated into potential novel therapeutic strategies for the treatment of the hematologic disorders in FA patients. PMID- 22675617 TI - Towards a molecular understanding of the fanconi anemia core complex. AB - Fanconi Anemia (FA) is a genetic disorder characterized by the inability of patient cells to repair DNA damage caused by interstrand crosslinking agents. There are currently 14 verified FA genes, where mutation of any single gene prevents repair of DNA interstrand crosslinks (ICLs). The accumulation of ICL damage results in genome instability and patients having a high predisposition to cancers. The key event of the FA pathway is dependent on an eight-protein core complex (CC), required for the monoubiquitination of each member of the FANCD2 FANCI complex. Interestingly, the majority of patient mutations reside in the CC. The molecular mechanisms underlying the requirement for such a large complex to carry out a monoubiquitination event remain a mystery. This paper documents the extensive efforts of researchers so far to understand the molecular roles of the CC proteins with regard to its main function in the FA pathway, the monoubiquitination of FANCD2 and FANCI. PMID- 22675619 TI - The Microcirculation Is Unchanged in Neonates with Severe Respiratory Failure after the Initiation of ECMO Treatment. AB - Purpose. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is known to improve cardiorespiratory function and outcome in neonates with severe respiratory failure. We tested the hypothesis that VA-ECMO therapy improves the microcirculation in neonates with severe respiratory failure. Methods. This single-center prospective observational pilot study took place in an intensive care unit of a level III university children's hospital. Twenty-one-term neonates, who received VA-ECMO treatment, were included. The microcirculation was assessed in the buccal mucosa, using Orthogonal Polarization Spectral imaging, within 24 hours before (T1) and within the first 24 hours after initiation of ECMO treatment (T2). Data were compared to data of a ventilated control group (N = 7). Results. At baseline (T1), median functional capillary density (FCD), microvascular flow index (MFI), and heterogeneity index (HI) did not differ between the ECMO group and the control group. At T2 the median FCD was lower in the control group (median [range]: 2.4 [1.4-4.2] versus 4.3 [2.8-7.4] cm/cm(2); P value <0.001). For MFI and HI there were no differences at T2 between the two groups. Conclusion. The perfusion of the microcirculation does not change after initiation of VA-ECMO treatment in neonates with severe respiratory failure. PMID- 22675618 TI - Advanced neuromonitoring and imaging in pediatric traumatic brain injury. AB - While the cornerstone of monitoring following severe pediatric traumatic brain injury is serial neurologic examinations, vital signs, and intracranial pressure monitoring, additional techniques may provide useful insight into early detection of evolving brain injury. This paper provides an overview of recent advances in neuromonitoring, neuroimaging, and biomarker analysis of pediatric patients following traumatic brain injury. PMID- 22675621 TI - An ultrasound study of cerebral venous drainage after internal jugular vein catheterization. AB - Objectives. It has been advocated that internal jugular vein (IJV) cannulation in patients at risk for intracranial hypertension could impair cerebral venous return. Aim of this study was to demonstrate that ultrasound-guided IJV cannulation in elective neurosurgical patients is safe and does not impair cerebral venous return. Methods. IJV cross-sectional diameter and flow were measured using two-dimensional ultrasound and Doppler function bilaterally before and after IJV cannulation with the head supine and elevated at 30 degrees . Results. Fifty patients with intracranial lesions at risk for intracranial hypertension were enrolled in this observational prospective study. IJV diameters before and after ultrasound-guided cannulation were not statistically different during supine or head-up position and the absolute variation of the venous flow revealed an average reduction of the venous flow after cannulation without a significant reduction of the venous flow rate after cannulation. Conclusions. Ultrasound-guided IJV cannulation in neurosurgical patients at risk for intracranial hypertension does not impair significantly jugular venous flow and indirectly cerebral venous return. PMID- 22675620 TI - Commonly used severity scores are not good predictors of mortality in sepsis from severe leptospirosis: a series of ten patients. AB - Introduction. Severe leptospirosis, also known as Weil's disease, can cause multiorgan failure with high mortality. Scoring systems for disease severity have not been validated for leptospirosis, and there is no documented method to predict mortality. Methods. This is a case series on 10 patients admitted to ICU for multiorgan failure from severe leptospirosis. Data were collected retrospectively, with approval from the Institution Ethics Committee. Results. Ten patients with severe leptospirosis were admitted in the Patras University Hospital ICU in a four-year period. Although, based on SOFA scores, predicted mortality was over 80%, seven of 10 patients survived and were discharged from the hospital in good condition. There was no association between SAPS II or SOFA scores and mortality, but survivors had significantly lower APACHE II scores compared to nonsurvivors. Conclusion. Commonly used severity scores do not seem to be useful in predicting mortality in severe leptospirosis. Early ICU admission and resuscitation based on a goal-directed therapy protocol are recommended and may reduce mortality. However, this study is limited by retrospective data collection and small sample size. Data from large prospective studies are needed to validate our findings. PMID- 22675622 TI - Alterations of the Erythrocyte Membrane during Sepsis. AB - Erythrocytes have been long considered as "dead" cells with transport of oxygen (O(2)) as their only function. However, the ability of red blood cells (RBCs) to modulate the microcirculation is now recognized as an important additional function. This capacity is regulated by a key element in the rheologic process: the RBC membrane. This membrane is a complex unit with multiple interactions between the extracellular and intracellular compartments: blood stream, endothelium, and other blood cells on the one hand, and the intracytoplasmic compartment with possible rapid adaptation of erythrocyte metabolism on the other. In this paper, we review the alterations in the erythrocyte membrane observed in critically ill patients and the influence of these alterations on the microcirculatory abnormalities observed in such patients. An understanding of the mechanisms of RBC rheologic alterations in sepsis and their effects on blood flow and on oxygen transport may be important to help reduce morbidity and mortality from severe sepsis. PMID- 22675623 TI - Prospective Associations between Religiousness/Spirituality and Depression and Mediating Effects of Forgiveness in a Nationally Representative Sample of United States Adults. AB - The present investigation examines the prospective associations of religiousness/spirituality with depression and the extent to which various dimensions of forgiveness act as mediating mechanisms of these associations. Data are from a nationally representative sample of United States adults who were first interviewed in 1998 and reinterviewed six months later. Measures of religiousness/spirituality, forgiveness, and various sociodemographics were collected. Depression was assessed using the Composite International Diagnostic Interview administered by trained interviewers. Results showed that religiousness/spirituality, forgiveness of oneself and others, and feeling forgiven by God were associated, both cross-sectionally and longitudinally, with depressive status. After controlling for initial depressive status, only forgiveness of oneself and others remained statistically significant predictors of depression. Path analyses revealed that religiousness/spirituality conveyed protective effects, prospectively, on depression by way of an indirect path through forgiveness of others but not forgiveness of oneself. Hence, forgiveness of others acts as a mechanism of the salutary effect of religiousness/spirituality, but forgiveness of oneself is an independent predictor. Conclusions regarding the continued development of this type of research and for the treatment of clients with depression are offered. PMID- 22675624 TI - Ductal carcinoma in situ: recent advances and future prospects. AB - Introduction. This article reviews current management strategies for DCIS in the context of recent randomised trials, including the role of sentinel lymph node biopsy (SLNB), adjuvant radiotherapy (RT) and endocrine treatment. Methods. Literature review facilitated by Medline, PubMed, Embase and Cochrane databases. Results. DCIS should be managed in the context of a multidisciplinary team. Local control depends upon clear surgical margins (at least 2 mm is generally acceptable). SLNB is not routine, but can be considered in patients undergoing mastectomy (Mx) with risk factors for occult invasion. RT following BCS significantly reduces local recurrence (LR), particularly in those at high-risk. There remains a lack of level-1 evidence supporting omission of adjuvant RT in selected low-risk cases. Large, multi-centric or recurrent lesions should be treated by Mx and immediate reconstruction should be discussed. Adjuvant hormonal treatment may reduce the risk of LR in selected cases with hormone sensitive disease. Conclusion. Further research is required to determine the role of new RT regimes and endocrine therapies. Biological profiling and molecular analysis represent an opportunity to improve our understanding of tumour biology in DCIS to rationalise treatment. Reliable identification of low-risk lesions could allow treatment to be less radical. PMID- 22675625 TI - The current state of targeted agents in rectal cancer. AB - Targeted biologic agents have an established role in treating metastatic colorectal cancer (CRC), and the integration of targeted therapies into the treatment of CRC has resulted in significant improvements in outcomes. Rapidly growing insight into the molecular biology of CRC, as well as recent developments in gene sequencing and molecular diagnostics, has led to high expectations for the identification of molecular markers to be used in personalized treatment regimens. The mechanisms of action and toxicities of targeted therapies differ from those of traditional cytotoxic chemotherapy. Targeted therapy has raised new insight about the possibility of tailoring treatment to an individual's disease, the assessment of drug effectiveness and toxicity, and the economics of cancer care. This paper covers the last decade of clinical trials that have explored the toxicity and efficacy of targeted agents in locally advanced and metastatic CRC and how their role may benefit patients with rectal cancer. Future efforts should include prospective studies of these agents in biomarker-defined subpopulations, as well as studies of novel agents that target angiogenesis, tumor-stromal interaction, and the cell signaling pathways implicated in rectal cancer. PMID- 22675626 TI - Functional mechanisms and roles of adaptor proteins in abl-regulated cytoskeletal actin dynamics. AB - Abl is a nonreceptor tyrosine kinase and plays an essential role in the modeling and remodeling of F-actin by transducing extracellular signals. Abl and its paralog, Arg, are unique among the tyrosine kinase family in that they contain an unusual extended C-terminal half consisting of multiple functional domains. This structural characteristic may underlie the role of Abl as a mediator of upstream signals to downstream signaling machineries involved in actin dynamics. Indeed, a group of SH3-containing accessory proteins, or adaptor proteins, have been identified that bind to a proline-rich domain of the C-terminal portion of Abl and modulate its kinase activity, substrate recognition, and intracellular localization. Moreover, the existence of signaling cascade and biological outcomes unique to each adaptor protein has been demonstrated. In this paper, we summarize functional roles and mechanisms of adaptor proteins in Abl-regulated actin dynamics, mainly focusing on a family of adaptor proteins, Abi. The mechanism of Abl's activation and downstream signaling mediated by Abi is described in comparison with those by another adaptor protein, Crk. PMID- 22675628 TI - Integration between Primary Care and Mental Health Services in Italy: Determinants of Referral and Stepped Care. AB - This study, carried out in the context of a collaborative care program for common mental disorders, is aimed at identifying the predictors of Primary Care Physician (PCP) referral to Community Mental Health Center (CMHC) and patterns of care. Patients with depression or anxiety disorders who had a first contact with CMHCs between January 1, 2007-December 31, 2009 were extracted from Bologna Local Health Authority database. A classification and regression tree procedure was used to determine which combination of demographic and diagnostic variables best distinguished patients referred by PCPs and to identify predictors of patterns of care (consultation, shared care, and treatment at the CMHC) for patients referred by PCPs. Of the 8570 patients, 57.4% were referred by PCPs. Those less likely to be referred by PCPs were living in the urban area, suffered from depressive disorder, and were young. As to the pattern of care, patients living in the urban area were more likely to receive shared care compared with those living in the nonurban area, while the reverse was true for consultation. Predictors of CMHC treatment were depression and young age. Prospective studies are needed to assess length, quantity, and quality of collaborative treatment for common mental disorder delivered at any step of care. PMID- 22675629 TI - Patient-related factors influencing satisfaction in the patient-doctor encounters at the general outpatient clinic of the university of calabar teaching hospital, calabar, Nigeria. AB - Medical consultation is at the centre of clinical practice. Satisfaction of a patient with this process is a major determinant of the clinical outcome. This study sought to determine the proportion of patients who were satisfied with their doctor-patient encounter and the patient-related factors that affected patients' satisfaction with the consultation process. A clinic-based, cross sectional study using a modified version of the General Practice Assessment Questionnaire (GPAQ), which employed a systematic sampling technique, was used. The questionnaires were administered on 430 patients within the ages of 18 years and 65 years. Among the 430 subjects within the ages of 18 years and 65 years studied, 200 (46.5%) were males and 230 (53.5%) were females. Only 59.3% were satisfied with their patient-doctor encounter. The patient's perception of time spent in the consultation, illness understanding after the visit, ability to cope with the illness after the visit, and ability to maintain health after visit were the only factors that affected patient's satisfaction with the consultation. In our environment, nonsatisfaction with the patient-doctor encounter is high. Only few factors considered to encourage a patients satisfaction at primary care consultation contributed to end-of-consultation satisfaction. This calls for refocusing so as to improve the overall patient care in our cultural context and meet the patient needs in our environment. PMID- 22675627 TI - Expression and Role of the Intermediate-Conductance Calcium-Activated Potassium Channel KCa3.1 in Glioblastoma. AB - Glioblastomas are characterized by altered expression of several ion channels that have important consequences in cell functions associated with their aggressiveness, such as cell survival, proliferation, and migration. Data on the altered expression and function of the intermediate-conductance calcium-activated K (KCa3.1) channels in glioblastoma cells have only recently become available. This paper aims to (i) illustrate the main structural, biophysical, pharmacological, and modulatory properties of the KCa3.1 channel, (ii) provide a detailed account of data on the expression of this channel in glioblastoma cells, as compared to normal brain tissue, and (iii) critically discuss its major functional roles. Available data suggest that KCa3.1 channels (i) are highly expressed in glioblastoma cells but only scantly in the normal brain parenchima, (ii) play an important role in the control of glioblastoma cell migration. Altogether, these data suggest KCa3.1 channels as potential candidates for a targeted therapy against this tumor. PMID- 22675630 TI - Seven-signal proteomic signature for detection of operable pancreatic ductal adenocarcinoma and their discrimination from autoimmune pancreatitis. AB - There is urgent need for biomarkers that provide early detection of pancreatic ductal adenocarcinoma (PDAC) as well as discrimination of autoimmune pancreatitis, as current clinical approaches are not suitably accurate for precise diagnosis. We used mass spectrometry to analyze protein profiles of more than 300 plasma specimens obtained from PDAC, noncancerous pancreatic diseases including autoimmune pancreatitis patients and healthy subjects. We obtained 1063 proteomic signals from 160 plasma samples in the training cohort. A proteomic signature consisting of 7 mass spectrometry signals was used for construction of a proteomic model for detection of PDAC patients. Using the test cohort, we confirmed that this proteomic model had discrimination power equal to that observed with the training cohort. The overall sensitivity and specificity for detection of cancer patients were 82.6% and 90.9%, respectively. Notably, 62.5% of the stage I and II cases were detected by our proteomic model. We also found that 100% of autoimmune pancreatitis patients were correctly assigned as noncancerous individuals. In the present paper, we developed a proteomic model that was shown able to detect early-stage PDAC patients. In addition, our model appeared capable of discriminating patients with autoimmune pancreatitis from those with PDAC. PMID- 22675631 TI - Sedentary Behavior and Physical Function Decline in Older Women: Findings from the Women's Health Initiative. AB - Sedentary behavior is associated with deleterious health outcomes. This study evaluated the association between sedentary time and physical function among postmenopausal women in the Women's Health Initiative Observational Study. Data for this prospective cohort study were collected between 1993-1998 (enrollment) and 2009, with an average of 12.3 follow-up years. Analyses included 61,609 women (aged 50-79 years at baseline). Sedentary time was estimated by questionnaire; physical function was measured using the RAND SF-36 physical function scale. Mixed-model analysis of repeated measures was used to estimate the relationship of sedentary time exposures and changes in physical function adjusting for relevant covariates. Compared to women reporting sedentary time of <=6 hours/day, those with greater amounts of sedentary time (>6-8 hours/day, >8-11 hours/day, >11 hours/day) reported lower physical function between baseline and follow up (coefficient = -0.78, CI = -0.98, -0.57, -1.48, CI = -1.71, -1.25, -3.13, and CI = -3.36, -2.89, respectively P < 0.001). Sedentary time was strongly associated with diminished physical function and most pronounced among older women and those reporting the greatest sedentary time. Maintaining physical function with age may be improved by pairing messages to limit sedentary activities with those promoting recommended levels of physical activity. PMID- 22675632 TI - Extension of Chronological Lifespan by Hexokinase Mutation in Kluyveromyces lactis Involves Increased Level of the Mitochondrial Chaperonin Hsp60. AB - Oxidative damage, mitochondrial dysfunction, genomic instability, and telomere shortening represent all molecular processes proposed as causal factors in aging. Lifespan can be increased by metabolism through an influence on such processes. Glucose reduction extends chronological lifespan (CLS) of Saccharomyces cerevisiae through metabolic adaptation to respiration. To answer the question if the reduced CLS could be ascribed to glucose per se or to glucose repression of respiratory enzymes, we used the Kluyveromyces lactis yeast, where glucose repression does not affect the respiratory function. We identified the unique hexokinase, encoded by RAG5 gene, as an important player in influencing yeast lifespan by modulating mitochondrial functionality and the level of the mitochondrial chaperonin Hsp60. In this context, this hexokinase might have a regulatory role in the influence of CLS, shedding new light on the complex regulation played by hexokinases. PMID- 22675633 TI - Biological effects of Mammalian translationally controlled tumor protein (TCTP) on cell death, proliferation, and tumorigenesis. AB - Translationally controlled tumor protein (TCTP) is a highly conserved protein found in eukaryotes, across animal and plant kingdoms and even in yeast. Mammalian TCTP is ubiquitously expressed in various tissues and cell types. TCTP is a multifunctional protein which plays important roles in a number of cell physiological events, such as immune responses, cell proliferation, tumorigenicity, and cell death, including apoptosis. Recent identification of TCTP as an antiapoptotic protein has attracted interest of many researchers in the field. The mechanism of antiapoptotic activity, however, has not been solved completely, and TCTP might inhibit other types of cell death. Cell death (including apoptosis) is closely linked to proliferation and tumorigenesis. In this context, we review recent findings regarding the role of TCTP in cell death, proliferation, and tumorigenesis and discuss the mechanisms. PMID- 22675635 TI - Application of echocardiography on transgenic mice with cardiomyopathies. AB - Cardiomyopathies are common cardiac disorders that primarily affect cardiac muscle resulting in cardiac dysfunction and heart failure. Transgenic mouse disease models have been developed to investigate the cellular mechanisms underlying heart failure and sudden cardiac death observed in cardiomyopathy cases and to explore the therapeutic outcomes in experimental animals in vivo. Echocardiography is an essential diagnostic tool for accurate and noninvasive assessment of cardiac structure and function in experimental animals. Our laboratory has been among the first to apply high-frequency research echocardiography on transgenic mice with cardiomyopathies. In this work, we have summarized our and other studies on assessment of systolic and diastolic dysfunction using conventional echocardiography, pulsed Doppler, and tissue Doppler imaging in transgenic mice with various cardiomyopathies. Estimation of embryonic mouse hearts has been performed as well using this high-resolution echocardiography. Some technical considerations in mouse echocardiography have also been discussed. PMID- 22675634 TI - Inhibition of the Mitochondrial Permeability Transition for Cytoprotection: Direct versus Indirect Mechanisms. AB - Mitochondria are fascinating organelles, which fulfill multiple cellular functions, as diverse as energy production, fatty acid beta oxidation, reactive oxygen species (ROS) production and detoxification, and cell death regulation. The coordination of these functions relies on autonomous mitochondrial processes as well as on sustained cross-talk with other organelles and/or the cytosol. Therefore, this implies a tight regulation of mitochondrial functions to ensure cell homeostasis. In many diseases (e.g., cancer, cardiopathies, nonalcoholic fatty liver diseases, and neurodegenerative diseases), mitochondria can receive harmful signals, dysfunction and then, participate to pathogenesis. They can undergo either a decrease of their bioenergetic function or a process called mitochondrial permeability transition (MPT) that can coordinate cell death execution. Many studies present evidence that protection of mitochondria limits disease progression and severity. Here, we will review recent strategies to preserve mitochondrial functions via direct or indirect mechanisms of MPT inhibition. Thus, several mitochondrial proteins may be considered for cytoprotective-targeted therapies. PMID- 22675636 TI - The "oblique popliteal ligament": a macro- and microanalysis to determine if it is a ligament or a tendon. AB - Introduction. This study investigated the importance of the "oblique popliteal ligament" (OPL), and challenges its alleged ligament status. The currently named OPL is indigenous to the distal semimembranosus (SMT); therefore, by definition is not a ligament inserting from bone to bone. Clinically, a muscle-tendon unit is different then a ligament regarding proprioception and surgery. Methods. Literature search was conducted on texts, journals and websites regarding the formation of the OPL. Dissection of 70 knees included macro analysis, harvesting OPL, distal SMT and LCL samples and performing immunohistochemistry to 16 knees with antibody staining to the OPL, distal SMT and LCL. Results. All but one text claimed the OPL receives fibers from SMT. Macro dissection of 70 knees revealed the OPL forming from the distal SMT (100%). Microanalysis of OPL, distal SMT and LCL samples from 16 knees demonstrated expression of nervous tissue within selected samples. Discussion. No journals or texts have hypothesized that the OPL is a tendon. Clinically it is important we know the type of tissue for purposes of maximizing rehabilitation and surgical techniques. Conclusion. This study suggests the OPL be considered the oblique popliteal tendon as a result of the macro and micro evidence revealed. PMID- 22675637 TI - Autologous stem cell transplant for Al amyloidosis. AB - AL amyloidosis is caused by clonal plasma cells that produce immunoglobulin light chains which misfold and get deposited as amyloid fibrils. Therapy directed against the plasma cell clone leads to clinical benefit. Melphalan and corticosteroids have been the mainstay of treatment for a number of years and the recent availability of other effective agents (IMiDs and proteasome inhibitors) has increased treatment options. Autologous stem cell transplant (ASCT) has been used in the treatment of AL amyloidosis for many years. It is associated with high rates of hematologic response and improvement in organ function. However, transplant carries considerable risks. Careful patient selection is important to minimize transplant related morbidity and mortality and ensure optimal patient outcomes. As newer more affective therapies become available the role and timing of ASCT in the overall treatment strategy of AL amyloidosis will need to be continually reassessed. PMID- 22675638 TI - Curability of multiple myeloma. AB - Among 792 patients with multiple myeloma treated from 1987 to 2010 and assessed after 18 months, there were 167 patients with complete remission. For those 60 patients treated between 1987-1998 and with long followup, the latest relapse occurred after 11.8 years, so that 13 patients have remained in sustained complete remission for longer than 12 years (range 12-22 years). These results suggest that 3% of all patients treated during that period may be cured of multiple myeloma. In addition to immunofixation, more sensitive techniques for the detection of residual disease should be applied more consistently in patients with apparent complete remission in order to identify those with potential cure. PMID- 22675639 TI - Increased alpha-Fetoprotein Predicts Steatosis among Patients with Chronic Hepatitis C Genotype 4. AB - Background. The prognostic importance of alpha-fetoprotein (AFP) level elevation in patients with chronic hepatitis C and its clinical significance in steatosis associated with HCV infection remain to be determined. The present paper assessed clinical significance of elevated AFP in patients with CHC with and without steatosis. Methods. One hundred patients with CHC were divided into 50 patients with CHC and steatosis and 50 patients with CHC and no steatosis based on liver biopsy. Results. AFP was significantly increased in CHC with steatosis than patients without steatosis (P < 0.001). Highly significant positive correlation was found between serum AFP and necroinflammation as well as the severity of fibrosis/cirrhosis and negative significant correlation with albumin level in chronic HCV with steatosis (P < 0.001) but negative nonsignificant correlation with ALT and AST level (P <= 0.778 and 0.398), respectively. Highly significant increase was found in chronic hepatitis patients with steatosis than CHC without steatosis regarding necroinflammation as well as the severity of fibrosis/cirrhosis and AFP (P < 0.001). Conclusion. Patients with chronic HCV and steatosis have a higher AFP levels than those without steatosis. In chronic HCV with steatosis, elevated AFP levels correlated positively with HAI and negative significant correlation with albumin level. PMID- 22675641 TI - Treatment outcomes and prognostic factors in mexican patients with endometrial carcinoma with emphasis on patients receiving radiotherapy after surgery: an institutional perspective. AB - Aim. To analyze the clinical characteristics and treatment outcomes in patients with endometrial carcinoma treated in a Latin American institute with emphasis in patients receiving adjuvant radiotherapy. Methods. A total of 412 patients with endometrial carcinoma admitted to our hospital between 1998 and 2008 were evaluated, retrospectively. The mean age was 55 years (28-87). Two hundred seventy patients received RT following surgery. Stage distribution was as follows: 221 patients (54%) stage I, 86 patients (21%) stage II, and 103 patients (24.5%) stage III and 2 patients (0.5%) stage IVA. Results. Overall survival rate was 95% at 2 years, 84% at 5 years, and 79% at 10 years. By the end of followup, 338 patients (82%) were disease-free, and 13 (3%) were alive with disease. Univariate and multivariate analyses identified age, grade, serosal and adnexial involvement as significant predictors for overall survival. Conclusion. The results of our study suggests that early-stage, low-grade endometrial cancer with no risk factors should not receive external beam radiotherapy, intermediate risk patients should receive only vaginal vault brachytherapy, and the use of chemotherapy with radiotherapy for patients high-risk and advanced-stage carcinoma the addition of radiotherapy is associated with a better survival being an effective therapeutic option. PMID- 22675640 TI - A review of fetal scarless healing. AB - Wound healing is a complex process involving a number of processes. Fetal regeneration has been shown to have a number of differences compared to scar forming healing. This review discusses the number of differences identified in fetal regeneration. Understanding these differences may result in new therapeutic targets which may reduce or even prevent scarring in adult healing. PMID- 22675642 TI - Epidemiological characteristics and survival studies of rhabdomyosarcoma in East egypt: a five-year multicenter study. AB - Background. Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children, it represents 5-8% of childhood malignancies. Aim of the Work. To evaluate the epidemiological characteristics and treatment outcome in two pediatric oncology centers. Patients and Method. A retrospective analysis was performed on 41 medical records of children with RMS during 6 years period. Results. The median age of patients was 6 years with 80.4% below 10 years. Head and neck was the most common primary site. Embryonal RMS was the most frequent histopathologic subtype. Stage IV was the most frequent stage. According to IRS postsurgical grouping classification, group 4 was the most frequent group. There was a significant relationship between histopathologic subtypes of tumor and metastasis, primary site of tumor and histopathologic subtype, age, metastasis, IRS presurgical stage and IRS postsurgical group and outcome. The overall survival rate was 56.9% +/- 8.4 and the failure free survival rate was 68.3% +/- 7.6. Conclusion. The epidemiological characteristics of our patients are quite near to the worldwide data, apart from the higher prevalence of stage IV and group 4 with most of the primary tumor site in the extremities. CWS2002 protocol of therapy had led to improvement in the curability of the disease. PMID- 22675643 TI - The retrourethral transobturator sling suspension in the treatment of male urinary stress incontinence: results of a single institution experience. AB - Objective. To evaluate functional outcome of the retrourethral transobturator sling suspension (RTS) in the treatment of stress urinary incontinence (SUI) caused by prior prostate surgery. Methods. The RTS (AdVance male sling) was implanted in 32 patients who suffered from mild to severe postsurgical-treatment incontinence at the University Hospital Ulm from September 2010 to September 2011 including 10 patients with prior radiation therapy. Functional data (uroflowmetry, daily pad use, and postvoid residual urine) as well as quality of life with impact of urinary problems (ICIQ-UI SF) were prospectively assessed at baseline and during followup. Results. After a median followup of 9 months (range, 3-14) the incontinence cure rate (no pad usage) was 56.2% and the improvement rate (1-2 pads/day or >=50% reduction) was 21.9%. No improvement was observed in 21.9%. Daily pad use and ICIQ-UI SF score improved significantly. No major perioperative complications occurred. Postoperatively, 15.6% of the patients exhibited transient acute urinary retention which resolved without further treatment after a maximum of 3 weeks. One patient underwent sling explantation due to dislocation and persistent perineal pain. Conclusions. The implantation of the RTS is a safe and effective procedure in selected patients with SUI resulting from prostate surgery. PMID- 22675644 TI - Necrotizing Fasciitis Associated with Staphylococcus lugdunensis. AB - Necrotizing fasciitis is a life-threatening soft tissue infection that results in rapid local tissue destruction. Type 1 necrotizing fasciitis is characterized by polymicrobial, synergistic infections that are caused by non-Group A streptococci, aerobic and anaerobic organisms. Type 2 necrotizing fasciitis involves Group A Streptococcus (GAS) with or without a coexisting staphylococcal infection. Here we provide the first report of necrotizing fasciitis jointly associated with the microbes Group B Streptococcus and Staphylococcus lugdunensis. S. lugdunensis is a commensal human skin bacterium known to cause often painful and prolonged skin and soft tissue infections. To our knowledge, however, this is the first case of Staph. lugdunensis-associated necrotizing fasciitis to be reported in the literature. PMID- 22675645 TI - Perianal plaques of cytomegalovirus in a patient with central nervous system lymphoma. AB - Cutaneous manifestations of cytomegalovirus (CMV) in patients without human immunodeficiency virus remain rare. Perianal CMV may be observed due to periodic fecal shedding but may be confused for other pathogens, and definitive diagnosis requires histopathologic examination. An instructive case is described, and the literature reviewed. PMID- 22675646 TI - Respiratory failure secondary to human metapneumovirus requiring extracorporeal membrane oxygenation in a 32-month-old child. AB - Human metapneumovirus (HMPV) is a common virus that can cause respiratory problems ranging from mild upper respiratory tract disease to respiratory failure requiring mechanical support. Here, we report a case of a 32-month-old male with a previous history of asthma, who developed respiratory failure two weeks after onset of cough and rhinorrhea and required extracorporeal membrane oxygenation (ECMO) for 9 days after failing high-frequency oscillatory ventilation (HFOV). To our knowledge, this is the oldest reported pediatric patient with respiratory failure secondary to human metapneumovirus that did not respond to mechanical ventilation. This case highlights three critical points: the potentially fatal causative role of HMPV in respiratory failure in an older pediatric age group of immunocompetent hosts, the importance of early recognition of impending respiratory failure, and the timely utilization of ECMO. PMID- 22675647 TI - Protective Function of STAT3 in CVB3-Induced Myocarditis. AB - The transcription factor signal transducer and activator of transcription 3 (STAT3) is an important mediator of the inflammatory process. We investigated the role of STAT3 in viral myocarditis and its possible role in the development to dilated cardiomyopathy. We used STAT3-deficent mice with a cardiomyocyte restricted knockout and induced a viral myocarditis using Coxsackievirus B3 (CVB3) which induced a severe inflammation during the acute phase of the viral myocarditis. A complete virus clearance and an attenuated inflammation were examined in both groups WT and STAT3 KO mice 4 weeks after infection, but the cardiac function in STAT3 KO mice was significantly decreased in contrast to the infected WT mice. Interestingly, an increased expression of collagen I was detected in STAT3 KO mice compared to WT mice 4 weeks after CVB3 infection. Furthermore, the matrix degradation was reduced in STAT3 KO mice which might be an explanation for the observed matrix deposition. Consequently, we here demonstrate the protective function of STAT3 in CVB3-induced myocarditis. Since the cardiomyocyte-restricted knockout leads to an increased fibrosis, it can be assumed that STAT3 signalling in cardiomyocytes protects the heart against increased fibrosis through paracrine effects. PMID- 22675648 TI - Tau Phosphorylation by GSK3 in Different Conditions. AB - Almost a 20% of the residues of tau protein are phosphorylatable amino acids: serine, threonine, and tyrosine. In this paper we comment on the consequences for tau of being a phosphoprotein. We will focus on serine/threonine phosphorylation. It will be discussed that, depending on the modified residue in tau molecule, phosphorylation could be protective, in processes like hibernation, or toxic like in development of those diseases known as tauopathies, which are characterized by an hyperphosphorylation and aggregation of tau. PMID- 22675649 TI - Microglial KCa3.1 Channels as a Potential Therapeutic Target for Alzheimer's Disease. AB - There exists an urgent need for new target discovery to treat Alzheimer's disease (AD); however, recent clinical trials based on anti-Abeta and anti-inflammatory strategies have yielded disappointing results. To expedite new drug discovery, we propose reposition targets which have been previously pursued by both industry and academia for indications other than AD. One such target is the calcium activated potassium channel KCa3.1 (KCNN4), which in the brain is primarily expressed in microglia and is significantly upregulated when microglia are activated. We here review the existing evidence supporting that KCa3.1 inhibition could block microglial neurotoxicity without affecting their neuroprotective phagocytosis activity and without being broadly immunosuppressive. The anti inflammatory and neuroprotective effects of KCa3.1 blockade would be suitable for treating AD as well as cerebrovascular and traumatic brain injuries, two well known risk factors contributing to the dementia in AD patients presenting with mixed pathologies. Importantly, the pharmacokinetics and pharmacodynamics of several KCa3.1 blockers are well known, and a KCa3.1 blocker has been proven safe in clinical trials. It is therefore promising to reposition old or new KCa3.1 blockers for AD preclinical and clinical trials. PMID- 22675650 TI - Dispensabilities of carbonic anhydrase in proteobacteria. AB - Carbonic anhydrase (CA) (E.C. 4.2.1.1) is a ubiquitous enzyme catalysing interconversion between CO(2) and bicarbonate. The irregular distribution of the phylogenetically distinct classes of CA in procaryotic genome suggests its complex evolutionary history in procaryotes. Genetic evidence regarding the dispensability of CA under high-CO(2) air in some model organisms indicates that CA-deficient microorganisms can persist in the natural environment by choosing high-CO(2) niches. In this study, we studied the distribution of CA in the genome of Proteobacteria. While a large majority of the genome-sequenced Proteobacteria retained a CA gene(s), intracellular bacterial genera such as Buchnera and Rickettsia contained CA-defective strains. Comparison between CA-retaining and CA deficient genomes showed the absence of whole coding sequence in some strains and the presence of frameshifted coding sequence in other strains. The evidence suggests that CA is inactivated and lost in some proteobacteria during the course of evolution based on its dispensability. PMID- 22675652 TI - Evolutionary History of Lake Tanganyika's Predatory Deepwater Cichlids. AB - Hybridization among littoral cichlid species in Lake Tanganyika was inferred in several molecular phylogenetic studies. The phenomenon is generally attributed to the lake level-induced shoreline and habitat changes. These allow for allopatric divergence of geographically fragmented populations alternating with locally restricted secondary contact and introgression between incompletely isolated taxa. In contrast, the deepwater habitat is characterized by weak geographic structure and a high potential for gene flow, which may explain the lower species richness of deepwater than littoral lineages. For the same reason, divergent deepwater lineages should have evolved strong intrinsic reproductive isolation already in the incipient stages of diversification, and, consequently, hybridization among established lineages should have been less frequent than in littoral lineages. We test this hypothesis in the endemic Lake Tanganyika deepwater cichlid tribe Bathybatini by comparing phylogenetic trees of Hemibates and Bathybates species obtained with nuclear multilocus AFLP data with a phylogeny based on mitochondrial sequences. Consistent with our hypothesis, largely congruent tree topologies and negative tests for introgression provided no evidence for introgressive hybridization between the deepwater taxa. Together, the nuclear and mitochondrial data established a well-supported phylogeny and suggested ecological segregation during speciation. PMID- 22675651 TI - Comparative pathogenomics of bacteria causing infectious diseases in fish. AB - Fish living in the wild as well as reared in the aquaculture facilities are susceptible to infectious diseases caused by a phylogenetically diverse collection of bacterial pathogens. Control and treatment options using vaccines and drugs are either inadequate, inefficient, or impracticable. The classical approach in studying fish bacterial pathogens has been looking at individual or few virulence factors. Recently, genome sequencing of a number of bacterial fish pathogens has tremendously increased our understanding of the biology, host adaptation, and virulence factors of these important pathogens. This paper attempts to compile the scattered literature on genome sequence information of fish pathogenic bacteria published and available to date. The genome sequencing has uncovered several complex adaptive evolutionary strategies mediated by horizontal gene transfer, insertion sequence elements, mutations and prophage sequences operating in fish pathogens, and how their genomes evolved from generalist environmental strains to highly virulent obligatory pathogens. In addition, the comparative genomics has allowed the identification of unique pathogen-specific gene clusters. The paper focuses on the comparative analysis of the virulogenomes of important fish bacterial pathogens, and the genes involved in their evolutionary adaptation to different ecological niches. The paper also proposes some new directions on finding novel vaccine and chemotherapeutic targets in the genomes of bacterial pathogens of fish. PMID- 22675654 TI - Whole-Genome Profiling of a Novel Mutagenesis Technique Using Proofreading Deficient DNA Polymerase delta. AB - A novel mutagenesis technique using error-prone DNA polymerase delta (poldelta), the disparity mutagenesis model of evolution, has been successfully employed to generate novel microorganism strains with desired traits. However, little else is known about the spectra of mutagenic effects caused by disparity mutagenesis. We evaluated and compared the performance of the poldeltaMKII mutator, which expresses the proofreading-deficient and low-fidelity poldelta, in Saccharomyces cerevisiae haploid strain with that of the commonly used chemical mutagen ethyl methanesulfonate (EMS). This mutator strain possesses exogenous mutant poldelta supplied from a plasmid, tthereby leaving the genomic one intact. We measured the mutation rate achieved by each mutagen and performed high-throughput next generation sequencing to analyze the genome-wide mutation spectra produced by the 2 mutagenesis methods. The mutation frequency of the mutator was approximately 7 times higher than that of EMS. Our analysis confirmed the strong G/C to A/T transition bias of EMS, whereas we found that the mutator mainly produces transversions, giving rise to more diverse amino acid substitution patterns. Our present study demonstrated that the poldeltaMKII mutator is a useful and efficient method for rapid strain improvement based on in vivo mutagenesis. PMID- 22675653 TI - Detection of horizontal gene transfers from phylogenetic comparisons. AB - Bacterial phylogenies have become one of the most important challenges for microbial ecology. This field started in the mid-1970s with the aim of using the sequence of the small subunit ribosomal RNA (16S) tool to infer bacterial phylogenies. Phylogenetic hypotheses based on other sequences usually give conflicting topologies that reveal different evolutionary histories, which in some cases may be the result of horizontal gene transfer events. Currently, one of the major goals of molecular biology is to understand the role that horizontal gene transfer plays in species adaptation and evolution. In this work, we compared the phylogenetic tree based on 16S with the tree based on dszC, a gene involved in the cleavage of carbon-sulfur bonds. Bacteria of several genera perform this survival task when living in environments lacking free mineral sulfur. The biochemical pathway of the desulphurization process was extensively studied due to its economic importance, since this step is expensive and indispensable in fuel production. Our results clearly show that horizontal gene transfer events could be detected using common phylogenetic methods with gene sequences obtained from public sequence databases. PMID- 22675655 TI - Genetic and Morphological Evidence Implies Existence of Two Sympatric Species in Cyathopharynx furcifer (Teleostei: Cichlidae) from Lake Tanganyika. AB - Although the cichlid fishes from Lake Tanganyika are treated as a textbook example of adaptive radiation, many taxonomic problems remain unresolved. Cyathopharynx furcifer, which belongs to the currently monospecific genus Cyathopharynx, contains two colour morphs at the southern end of the lake: one has a yellow anal fin, and the other has a black anal fin. Some books for hobbyists of ornamental fish treat these morphs as different species, but taxonomic studies have neither mentioned the existence nor addressed the status of these colour morphs. In the present paper, we analysed these two colour morphs using mitochondrial, microsatellite, morphometric, and meristic data sets. Both molecular and morphological data allowed clear discrimination between these morphs, suggesting the existence of two distinct sympatric species. Three taxonomic species have been described in this genus, and only C. furcifer is currently considered valid. Observations of type specimens of these three nominal species will be needed to determine the scientific names of these colour morphs. PMID- 22675656 TI - Comparison of different anthropometric measurements and inflammatory biomarkers. AB - Introduction. Different anthropometric variables have been shown to be related to cardiovascular morbidity and mortality. Our aim was to compare the association between different anthropometric measurements and inflammatory status. Methods and results. A cross-sectional study design in which we analyzed the data collected during a five-year period in the Tel Aviv Medical Center Inflammation Survey (TAMCIS). Included in the study were 13,033 apparently healthy individuals at a mean (SD) age of 43. Of these, 8,292 were male and 4,741 female. A significant age-adjusted and multiple-adjusted partial correlation was noted between all anthropometric measurements and all inflammatory biomarkers. There was no significant difference in the correlation coefficients between different biomarkers and anthropometric variables. Conclusion. Most of the common used anthropometric variables are similarly correlated with inflammatory variables. The clinician can choose the variable that he/she finds easiest to use. PMID- 22675657 TI - Voltammetric determination of homocysteine using multiwall carbon nanotube paste electrode in the presence of chlorpromazine as a mediator. AB - We propose chlorpromazine (CHP) as a new mediator for the rapid, sensitive, and highly selective voltammetric determination of homocysteine (Hcy) using multiwall carbon nanotube paste electrode (MWCNTPE). The experimental results showed that the carbon nanotube paste electrode has a highly electrocatalytic activity for the oxidation of Hcy in the presence of CHP as a mediator. Cyclic voltammetry, double potential step chronoamperometry, and square wave voltammetry (SWV) are used to investigate the suitability of CHP at the surface of MWCNTPE as a mediator for the electrocatalytic oxidation of Hcy in aqueous solutions. The kinetic parameters of the system, including electron transfer coefficient, and catalytic rate constant were also determined using the electrochemical approaches. In addition, SWV was used for quantitative analysis. SWV showed wide linear dynamic range (0.1-210.0 MUM Hcy) with a detection limit of 0.08 MUM Hcy. Finally, this method was also examined as a selective, simple, and precise electrochemical sensor for the determination of Hcy in real samples. PMID- 22675659 TI - Proteolytic degradation of amyloid beta-protein. AB - The amyloid beta-protein (Abeta) is subject to proteolytic degradation by a diverse array of peptidases and proteinases, known collectively as Abeta degrading proteases (AbetaDPs). A growing number of AbetaDPs have been identified, which, under physiological and/or pathophysiological conditions, contribute significantly to the determination of endogenous cerebral Abeta levels. Despite more than a decade of investigation, the complete set of AbetaDPs remains to be established, and our understanding of even well-established AbetaDPs is incomplete. Nevertheless, the study of known AbetaDPs has contributed importantly to our understanding of the molecular pathogenesis of Alzheimer disease (AD) and has inspired the development of several novel therapeutic approaches to the regulation of cerebral Abeta levels. In this article, we discuss the general features of Abeta degradation and introduce the best characterized AbetaDPs, focusing on their diverse properties and the numerous conceptual insights that have emerged from the study of each. PMID- 22675658 TI - Biochemistry of amyloid beta-protein and amyloid deposits in Alzheimer disease. AB - Progressive cerebral deposition of the amyloid beta-protein (Abeta) in brain regions serving memory and cognition is an invariant and defining feature of Alzheimer disease. A highly similar but less robust process accompanies brain aging in many nondemented humans, lower primates, and some other mammals. The discovery of Abeta as the subunit of the amyloid fibrils in meningocerebral blood vessels and parenchymal plaques has led to innumerable studies of its biochemistry and potential cytotoxic properties. Here we will review the discovery of Abeta, numerous aspects of its complex biochemistry, and current attempts to understand how a range of Abeta assemblies, including soluble oligomers and insoluble fibrils, may precipitate and promote neuronal and glial alterations that underlie the development of dementia. Although the role of Abeta as a key molecular factor in the etiology of Alzheimer disease remains controversial, clinical trials of amyloid-lowering agents, reviewed elsewhere in this book, are poised to resolve the question of its pathogenic primacy. PMID- 22675661 TI - Myeloid cells and lymphangiogenesis. AB - The lymphatic vascular system and the hematopoietic system are intimately connected in ontogeny and in physiology. During embryonic development, mammalian species derive a first lymphatic vascular plexus from the previously formed anterior cardinal vein, whereas birds and amphibians have a lymphatic vascular system of dual origin, composed of lymphatic endothelial cells (LECs) of venous origin combined with LECs derived from mesenchymal lymphangioblasts. The contribution of hematopoietic cells as building blocks of nascent lymphatic structures in mammals is still under debate. In contrast, the importance of myeloid cells to direct lymphatic vessel growth and function postnatally has been experimentally shown. For example, myeloid cells communicate with LECs via paracrine factors or cell-cell contacts, and they also can acquire lymphatic endothelial morphology and marker gene expression, a process reminiscent of developmental vasculogenesis. Here, we present an overview of the current understanding of how lymphatic vessels and the hematopoietic system, in particular myeloid cells, interact during embryonic development, in normal organ physiology, and in disease. PMID- 22675660 TI - Antiangiogenic therapy for ischemic retinopathies. AB - Neovascularization is a common pathological process in various retinal vascular disorders including diabetic retinopathy (DR), age-related macular degeneration (AMD) and retinal vein occlusion (RVO). The development of neovascular vessels may lead to complications such as vitreous hemorrhage, fibrovascular tissue formation, and traction retinal detachments. Ultimately, irreversible vision loss may result. Various proangiogenic factors are involved in these complex processes. Different antiangiogenic drugs have been formulated in an attempt treat these vascular disorders. One factor that plays a major role in the development of retinal neovascularization is vascular endothelial growth factor (VEGF). Anti-VEGF agents are currently FDA approved for the treatment of AMD and RVO. They are also extensively used as an off-label treatment for diabetic macular edema (DME), proliferative DR, and neovascular glaucoma. However, at this time, the long-term safety of chronic VEGF inhibition has not been extensively evaluated. A large and rapidly expanding body of research on angiogenesis is being conducted at multiple centers across the globe to determine the exact contributions and interactions among a variety of angiogenic factors in an effort to determine the therapeutic potential of antiangiogenic agent in the treatment of a variety of retinal diseases. PMID- 22675662 TI - HIV-1-related central nervous system disease: current issues in pathogenesis, diagnosis, and treatment. AB - HIV-associated central nervous system (CNS) injury continues to be clinically significant in the modern era of HIV infection and therapy. A substantial proportion of patients with suppressed HIV infection on optimal antiretroviral therapy have impaired performance on neuropsychological testing, suggesting persistence of neurological abnormalities despite treatment and projected long term survival. In the underresourced setting, limited accessibility to antiretroviral medications means that CNS complications of later-stage HIV infection continue to be a major concern. This article reviews key recent advances in our understanding of the neuropathogenesis of HIV, focusing on basic and clinical studies that reveal viral and host features associated with viral neuroinvasion, persistence, and immunopathogenesis in the CNS, as well as issues related to monitoring and treatment of HIV-associated CNS injury in the current era. PMID- 22675664 TI - Generating beta cells from stem cells-the story so far. AB - Despite intensive research, a treatment for diabetic patients that completely restores normoglycemia for an indefinite period of time remains elusive. Although islet transplantation temporarily confers normoglycemia to patients, the lack of a renewable source of insulin-producing beta cells hampers the use of this treatment option. Although significant hurdles remain, recent advances in stem cell biology indicate that generation of fully matured beta cells from uncommitted progenitor cells, including human embryonic stem cells and induced pluripotent stem cells derived from somatic cell populations, is becoming an achievable goal. PMID- 22675663 TI - Lessons in nonhuman primate models for AIDS vaccine research: from minefields to milestones. AB - Nonhuman primate (NHP) disease models for AIDS have made important contributions to the search for effective vaccines for AIDS. Viral diversity, persistence, capacity for immune evasion, and safety considerations have limited development of conventional approaches using killed or attenuated vaccines, necessitating the development of novel approaches. Here we highlight the knowledge gained and lessons learned in testing vaccine concepts in different virus/NHP host combinations. PMID- 22675665 TI - Immunologic and metabolic biomarkers of beta-cell destruction in the diagnosis of type 1 diabetes. AB - Type 1 diabetes (T1D), also known as insulin-dependent diabetes mellitus, is a chronic disorder that results from autoimmune destruction of insulin-producing beta cells in the islets of Langerhans within the pancreas ( Atkinson and Maclaren 1994). This disease becomes clinically apparent only after significant destruction of the beta-cell mass, which reduces the ability to maintain glycemic control and metabolic function. In addition, it continues for years after clinical onset until, generally, there is complete destruction of insulin secretory capacity. Because prevention and therapy strategies are targeted to this pathologic process, it becomes imperative to have methods with which it can be monitored. This work discusses current research-based approaches to monitor the autoimmunity and metabolic function in T1D patients and their potential for widespread clinical application. PMID- 22675666 TI - Clinical approach to Parkinson's disease: features, diagnosis, and principles of management. AB - Parkinson's disease (PD) is one of the most common neurodegenerative disorders. The condition causes a heavy burden both on those affected, as well as their families. Accurate diagnosis is critical and remains founded on clinical grounds as no specific diagnostic test is available so far. The clinical picture of PD is typical in many instances; however, features distinguishing it from other disorders should be thoroughly sought. Monogenic forms of PD also have some distinctive characteristics in many cases. This text is a roadmap to accurate diagnosis in PD, as it approaches clinical features, diagnostic methodology, and leading differential diagnoses. Therapeutic issues are also briefly discussed. PMID- 22675667 TI - Motor control abnormalities in Parkinson's disease. AB - The primary manifestations of Parkinson's disease are abnormalities of movement, including movement slowness, difficulties with gait and balance, and tremor. We know a considerable amount about the abnormalities of neuronal and muscle activity that correlate with these symptoms. Motor symptoms can also be described in terms of motor control, a level of description that explains how movement variables, such as a limb's position and speed, are controlled and coordinated. Understanding motor symptoms as motor control abnormalities means to identify how the disease disrupts normal control processes. In the case of Parkinson's disease, movement slowness, for example, would be explained by a disruption of the control processes that determine normal movement speed. Two long-term benefits of understanding the motor control basis of motor symptoms include the future design of neural prostheses to replace the function of damaged basal ganglia circuits, and the rational design of rehabilitation strategies. This type of understanding, however, remains limited, partly because of limitations in our knowledge of normal motor control. In this article, we review the concept of motor control and describe a few motor symptoms that illustrate the challenges in understanding such symptoms as motor control abnormalities. PMID- 22675669 TI - Rational development of addiction pharmacotherapies: successes, failures, and prospects. AB - There are currently effective, U.S. Food and Drug Administration (FDA)-approved therapies for alcohol, nicotine, and opioid addiction. In some cases these therapeutics were rationally designed and tested using a combination of various animal models of addiction. In many cases, however, effective drug therapies for addiction were derived from the testing of compounds developed for other CNS disorders (e.g., analgesics and antidepressants), which were tested clinically in the absence of prior animal research using addiction models. This article will review the development of eight compounds that are currently most effective in the treatment of alcohol, opioid, and nicotine addiction with an emphasis on pharmacological mechanisms as well as the utility of animal models of addiction in the development of these therapeutics. In contrast to these successes, animal research has identified a number of promising medications for the treatment of psychostimulant addiction, none of which have proven to be effective clinically. This raises questions about the validity of current animal models of psychostimulant addiction. A specific example of an apparently promising pharmacotherapeutic for cocaine addiction (the D1 dopamine receptor antagonist ecopipam) that failed clinically will be examined to determine if this truly represents a challenge to the predictive validity of current models of cocaine addiction. In addition, the development of promising cocaine addiction therapeutics derived from animal research will be reviewed. PMID- 22675670 TI - Advanced Donor Age Impairs Bone Marrow Cell Therapeutic Efficacy for Cardiac Disease. AB - Therapeutic results of clinical autologous bone marrow cell (BMC) therapy trials for cardiac disease have been modest compared to results of BMC implantation into rodent hearts post-myocardial infarction (MI). In clinical trials, autologous BMCs are typically harvested from older patients who have recently suffered an MI. In contrast, experimental studies in rodent models typically utilize donor BMCs isolated from young, healthy, inbred mice that are not the recipients. Using unfractionated BMCs from donor mice at ages of young, middle-aged, and old, we discovered that recipient left ventricular function post-MI was significantly improved by young donor BMC implantation but was only preserved by middle-aged donor BMCs. Notably, old donor BMCs did not slow the decline in recipient post-MI cardiac function, suggesting BMC impairment by advanced donor age. Furthermore, we also show here that BMCs that are therapeutically impaired by donor age can be further impaired by concurrent donor MI. In conclusion, our findings suggest that therapeutic impairment of BMCs by advanced age is one of the important factors that can limit the success of clinical autologous BMC-based therapy. PMID- 22675668 TI - Physiology of epithelial chloride and fluid secretion. AB - Epithelial salt and water secretion serves a variety of functions in different organ systems, such as the airways, intestines, pancreas, and salivary glands. In cystic fibrosis (CF), the volume and/or composition of secreted luminal fluids are compromised owing to mutations in the gene encoding CFTR, the apical membrane anion channel that is responsible for salt secretion in response to cAMP/PKA stimulation. This article examines CFTR and related cellular transport processes that underlie epithelial anion and fluid secretion, their regulation, and how these processes are altered in CF disease to account for organ-specific secretory phenotypes. PMID- 22675671 TI - Survival function of the FADD-CASPASE-8-cFLIP(L) complex. AB - Caspase-8, the initiator caspase of the death receptor pathway of apoptosis, its adapter molecule, FADD, required for caspase-8 activation, and cFLIPL, a caspase 8-like protein that lacks a catalytic site and blocks caspase-8-mediated apoptosis, are each essential for embryonic development. Animals deficient in any of these genes present with E10.5 embryonic lethality. Recent studies have shown that development in caspase-8-deficient mice is rescued by ablation of RIPK3, a kinase that promotes a form of programmed, necrotic cell death. Here, we show that FADD, RIPK3 double-knockout mice develop normally but that the lethal effects of cFLIP deletion are not rescued by RIPK3 deficiency. Remarkably, in mice lacking FADD, cFLIP, and RIPK3, embryonic development is normal. This can be explained by the convergence of two cell processes: the enzymatic activity of the FADD-caspase-8-cFLIPL complex blocks RIPK3-dependent signaling (including necrosis), whereas cFLIPL blocks RIPK3-independent apoptosis promoted by the FADD caspase-8 complex. PMID- 22675674 TI - Anaphylaxis--recognition and management. AB - BACKGROUND: Anaphylaxis is a rapid onset, multisystem hypersensitivity reaction. The diagnosis is usually straightforward, but may be difficult when skin signs are absent. OBJECTIVE: This article describes the recognition, assessment and evidence based management of anaphylaxis in the general practice setting. DISCUSSION: Published guidelines on the management of anaphylaxis are broadly consistent and emphasise the early use of intramuscular adrenaline, supine position, airway support and intravenous fluid resuscitation. Intravenous bolus doses of adrenaline should be avoided unless cardiac arrest occurs. Steroids and antihistamines have no proven role and are not recommended as first line management. As protracted or biphasic reactions can occur, patients should be observed in the emergency department setting for at least 6 hours after an acute event. Follow up aims to provide accurate identification of likely cause(s) to help prevent further exposure, immunotherapy if available and an action plan and adrenaline auto-injector where further accidental exposures are likely. PMID- 22675672 TI - Homeostatic imbalance and colon cancer: the dynamic epigenetic interplay of inflammation, environmental toxins, and chemopreventive plant compounds. AB - The advent of modern medicine has allowed for significant advances within the fields of emergency care, surgery, and infectious disease control. Health threats that were historically responsible for immeasurable tolls on human life are now all but eradicated within certain populations, specifically those that enjoy higher degrees of socio-economic status and access to healthcare. However, modernization and its resulting lifestyle trends have ushered in a new era of chronic illness; one in which an unprecedented number of people are estimated to contract cancer and other inflammatory diseases. Here, we explore the idea that homeostasis has been redefined within just a few generations, and that diseases such as colorectal cancer are the result of fluctuating physiological and molecular imbalances. Phytochemical-deprived, pro-inflammatory diets combined with low-dose exposures to environmental toxins, including bisphenol-A (BPA) and other endocrine disruptors, are now linked to increasing incidences of cancer in westernized societies and developing countries. There is recent evidence that disease determinants are likely set in utero and further perpetuated into adulthood dependent upon the innate and environmentally acquired phenotype unique to each individual. In order to address a disease as multi-factorial, case specific, and remarkably adaptive as cancer, research must focus on its root causes in order to elucidate the molecular mechanisms by which they can be prevented or counteracted via plant-derived compounds such as epigallocatechin-3 gallate (EGCG) and resveratrol. The significant role of epigenetics in the regulation of these complex processes is emphasized here to form a comprehensive view of the dynamic interactions that influence modern-day carcinogenesis, and how sensibly restoring homeostatic balance may be the key to the cancer riddle. PMID- 22675675 TI - Thermal burns--assessment and acute management in the general practice setting. AB - BACKGROUND: Appropriate care of minor burns is key if complications, leading to the need for surgical intervention and increased likelihood of poor outcomes, are to be avoided. OBJECTIVE: This article provides guidance to support the appropriate management of thermal burns in the general practice setting. DISCUSSION: Correct initial assessment of the patient with a thermal burn will determine whether they can be managed at home or require burns unit care, hospital admission for analgesia or specialist outpatient review. Factors that may impact on healing include the size, depth and location of the wound; the presence of oedema and blisters; as well as the patient's social circumstances, age and health status. First aid with cool running water should be applied to the burn for at least 20 minutes. Cooling and the application of an occlusive dressing will minimise the pain associated with partial thickness burns. Oral analgesics or short term hospital admission for adequate pain control may be necessary. Definitive management of minor burns involves dressings, rest, elevation and oedema control, and regular review as the burn wound evolves and heals. Referral should be considered for any burn wound that appears unlikely to heal within 14 days postinjury. PMID- 22675676 TI - Survival radiology for GPs. AB - BACKGROUND: General practitioners in regional and rural areas may be required to interpret emergency imaging of their patients without the immediate assistance of a radiologist. OBJECTIVE: To provide a structured approach to interpretation of X rays performed as part of routine care of common emergency presentations. DISCUSSION: X-rays are an important diagnostic tool and should follow a complete history and examination. A structured approach and awareness of potential pitfalls will enable the primary care doctor to confidently interpret plain X rays in emergency situations. PMID- 22675677 TI - Basic and advanced cardiac life support--what's new? AB - BACKGROUND: Australian Resuscitation Council guidelines on basic and advanced life support are amended periodically. These changes are informed by recent evidence on best practice in resuscitation medicine. In December 2010, the latest guidelines were released for implementation in 2011. OBJECTIVE: This article outlines the key messages from the latest Australian Resuscitation Council guidelines on basic and advanced life support. DISCUSSION: The latest Australian Resuscitation Council guidelines on basic and advanced life support emphasise the importance of early recognition of deterioration before cardiac arrest. Once resuscitation commences, there is a focus on early defibrillation and early chest compressions with a simplification of drug treatment. Postresuscitation phase changes emphasise early intervention to re-establish coronary artery patency and therapeutic hypothermia. PMID- 22675673 TI - Radiation, inflammation, and immune responses in cancer. AB - Chronic inflammation has emerged as one of the hallmarks of cancer. Inflammation also plays a pivotal role in modulating radiation responsiveness of tumors. As discussed in this review, ionizing radiation (IR) leads to activation of several transcription factors modulating the expression of numerous mediators in tumor cells and cells of the microenvironment promoting cancer development. Novel therapeutic approaches thus aim to interfere with the activity or expression of these factors, either in single-agent or combinatorial treatment or as supplements of the existing therapeutic concepts. Among them, NF-kappaB, STAT-3, and HIF-1 play a crucial role in radiation-induced inflammatory responses embedded in a complex inflammatory network. A great variety of classical or novel drugs including nutraceuticals such as plant phytochemicals have the capacity to interfere with the inflammatory network in cancer and are considered as putative radiosensitizers. Thus, targeting the inflammatory signaling pathways induced by IR offers the opportunity to improve the clinical outcome of radiation therapy by enhancing radiosensitivity and decreasing putative metabolic effects. Since inflammation and sex steroids also impact tumorigenesis, a therapeutic approach targeting glucocorticoid receptors and radiation-induced production of tumorigenic factors might be effective in sensitizing certain tumors to IR. PMID- 22675678 TI - Oral glucose tolerance testing. AB - The oral glucose tolerance test (OGTT) is currently the gold standard for the diagnosis of diabetes. The recommended preparation for and administration of the OGTT are important to ensure that test results are not affected. Interpretation is based on venous plasma glucose results before and 2 hours after a 75 g oral glucose load. PMID- 22675679 TI - Acute infective endophthalmitis--case studies in ophthalmic emergencies. PMID- 22675680 TI - Nocturia--a guide to assessment and management. AB - BACKGROUND: Nocturia is a common cause of sleep disturbance affecting up to 40% of the adult population. OBJECTIVE: This article provides a framework for the management of nocturia. Based on the frequency volume chart, nocturia can be divided into three categories: global polyuria, nocturnal polyuria and bladder storage disorders. Differentiating between these categories enables effective targeting of treatment. DISCUSSION: Although nocturia is one of the most bothersome urinary symptoms, it has generally been poorly understood and managed. Aetiology is often multifactorial and includes systemic medical disease, lower urinary tract pathology, sleep disorders and behavioural and environmental factors. PMID- 22675681 TI - Vaccines and risk of lymphoedema--a case report of a breast cancer patient. AB - BACKGROUND: Vaccinations have been linked to lymphoedema but there is no quality scientific evidence to support or refute a causative relationship. OBJECTIVE: We report on a case of a breast cancer patient who developed lymphoedema following vaccination in her 'at risk' arm. She had previously undergone mastectomy and axillary clearance but did not have lymphoedema before the vaccinations. DISCUSSION: The risk of lymphoedema is still present for many years following breast surgery. Patients who are at risk of lymphoedema should be warned to report persistent swelling after vaccination so that they can be referred early for physiotherapy intervention if required. PMID- 22675682 TI - Great toenail deformity--case studies. PMID- 22675683 TI - Iliac fossa pain in pregnancy--a case study. PMID- 22675684 TI - A missed opportunity--lessons learnt from a chlamydia testing observation study in general practice. AB - BACKGROUND: Chlamydia is the most frequently notified sexually transmissible infection in Australia and occurs most commonly in young people. Up to 80% of chlamydia infections are asymptomatic. The Royal Australian College of General Practitioners recommends annual chlamydia testing for all sexually active people aged less than 25 years. This study explored potential structural or procedural barriers that might inhibit chlamydia testing in young women in general practice. METHODS: The chlamydia testing pathways of 12 general practices were examined using a comprehensive practice assessment tool. The pathways of these clinics were compared to a best practice testing pathway, and clinics were offered tailored advice to help improve their practice pathway. RESULTS: Clinics were followed up at 2 months. Little change to existing practices had been made. DISCUSSION: Clinics employing a practice manager were better equipped to enable systems for chlamydia testing to be developed. Results are discussed in light of May's normalisation theory, which states that changing practices requires shared understanding and commitment by all staff. It is unlikely that chlamydia testing rates in general practice will reach the levels required to reduce the burden of chlamydia without a coordinated clinic level approach. PMID- 22675685 TI - General practice research--does gender affect the decision to participate? AB - BACKGROUND: Recruitment of general practitioners for research in Australia is problematic. We aimed to explore general practice demographics and recent research experience for effects on research attitudes and enablers and inhibitors of research participation. METHODS: A survey was developed and distributed to GPs via two divisions of general practice in Melbourne, Victoria. RESULTS: Seven hundred and fifty-six questionnaires were mailed and 215 (28%) returned; 50% of respondents were women and 51% of all GPs had previously participated in general practice research. Gender differences were found in factors affecting the decision to participate. Women were significantly more concerned about out-of hours commitment (p<0.001), paperwork volume (p<0.001), recruitment criteria (p=0.009) and research methodology complexity (p=0.016). They were more likely to want to work as a general practice group (p=0.007) and to be inhibited by having to present results to peers (OR 2.4, 95% CI: 1.5-3.8). CONCLUSION: Research challenges, reduced interest in research participation and feminisation of the workforce have major implications for the future of research in general practice. Systemic changes are needed to address these issues. PMID- 22675686 TI - Community development--improving patient safety by enhancing the use of health services. AB - BACKGROUND: Community development plays an important role in increasing the access of disadvantaged groups to resources and services. We examined how community development in primary healthcare services may improve patient safety by involving people in activities that lead to their enhanced use of services. METHODS: Audits of service activity and 68 in-depth interviews at six primary healthcare services in South Australia and the Northern Territory. Managers, practitioners and administration staff, plus regional health service executives and departmental funders participated in the interviews. RESULTS: Each of the services undertook some community development. Reported benefits included engaging people in health promoting activity, providing people with social contacts and, crucially, encouraging people to use health services. DISCUSSION: Community development is a means of engaging people who, for a range of reasons, are reluctant to use services and therefore can increase patient safety. PMID- 22675687 TI - Registrar medical educators--experiences in the Australian General Practice Training Program 2005-11. AB - BACKGROUND: Increasingly, regional training providers employ general practice registrars within their medical education teams. Until recently, only anecdotal evidence has been available about registrar medical educators. METHODS: We surveyed current and past registrar medical educators working in the Australian General Practice Training Program from 2005 to 2011, examining demographics, motivations, roles and responsibilities, attitudes and future career intentions. RESULTS: Of 45 known registrar medical educators, 30 responded to our survey. Most were female (83%) and motivated by a desired career in medical education or were seeking diversity. Registrar educators undertook the full scope of educational activities and demonstrated a willingness to become more involved in policy, research and creating resources for registrars. DISCUSSION: The role of registrar medical educators appears to fill a need both for the individual registrar and for the Australian General Practice Training Program program as a whole. PMID- 22675688 TI - The Aboriginal Medical Service Redfern--improving access to primary care for over 40 years. AB - The health and life expectancy gap between Indigenous and non-Indigenous Australians is well known. Over 60% of Aboriginal and Torres Strait Islander people live in capital cities or regional centres. The Aboriginal Medical Service Redfern has been providing accessible primary healthcare to this population for over 40 years. This article describes the work of the Aboriginal Medical Service Redfern and reflects on strategies to improve access to primary care services for Aboriginal and Torres Strait Islander people. PMID- 22675689 TI - The 'pet effect'--health related aspects of companion animal ownership. AB - BACKGROUND: Numerous studies indicate that companion animal ownership is associated with a range of physical, psychological and social health advantages, yet there is little discussion around the practical ways to integrate companion animals into healthcare and health promotion. OBJECTIVE: This article provides a brief summary of the health related aspects of companion animal ownership, and suggests ways in which general practitioners can integrate discussions regarding pet interaction into everyday practice. DISCUSSION: The subject of companion animals can be a catalyst for engaging patients in discussions about preventive health. General practitioners are in an ideal position to understand the human pet dynamic, and to encourage patients to interact with their pets to improve their own health and wellbeing. Questions relating to companion animals could be asked during routine social history taking. The knowledge gained from this approach may facilitate more tailored patient management and personalised lifestyle recommendations. PMID- 22675690 TI - What is evidence-based practice and how do we get there? PMID- 22675691 TI - Why do we always end up here? Evidence-based medicine's conceptual cul-de-sacs and some off-road alternative routes. PMID- 22675692 TI - The case for practice-based evidence to support evidence-based practice. PMID- 22675693 TI - Access in New Zealand to antidotes for accidental and intentional drug poisonings. AB - INTRODUCTION: Access to antidotes for the treatment of drug poisonings can impact on morbidity and mortality. Treatment for drug poisonings usually occurs at the nearest emergency department; however, health professionals working in primary care are often the first point of contact for patients. As New Zealand has a small, diffuse population, and poisonings are a rare event, it can be difficult to anticipate what antidotes are required. AIM: The aim of the study was to determine what antidotes are frequently used and stocked in hospital pharmacies. METHODS: A survey was sent out to all 25 hospital pharmacies, excluding private and satellite hospitals. The survey contained questions about the stocking, and prior use, of over 30 antidotes. Also included were open-ended questions asking about reasons for not stocking antidotes and procedures for procuring antidotes in an emergency. RESULTS: Twenty out of 25 hospital pharmacies completed the survey. Most hospital pharmacies were found to stock large quantities of commonly used antidotes and low quantities of uncommonly used antidotes-but in sufficient quantity to treat one to two patients. A low number of poisonings was the most common reason cited for not stocking antidotes, followed by high cost. Most hospitals had clear guidelines for procuring and lending antidotes in an emergency. DISCUSSION: New Zealand hospital pharmacies stock adequate quantities of most antidotes, including antidotes that are expensive and rarely required, but which may be needed urgently. Hospital pharmacies also have clear procurement procedures for obtaining other antidotes in an emergency. PMID- 22675694 TI - Prescription drug misuse: quantifying the experiences of New Zealand GPs. AB - INTRODUCTION: The misuse of prescription drugs for their psychoactive effects is an international problem. To date, there is a paucity of quantitative data on prescription drug misuse (PDM) in New Zealand, especially data investigating the experiences of general practitioners (GPs). AIM: To quantify GPs' experiences regarding PDM in New Zealand in terms of the extent of the problem, challenges faced, problem drugs, and actions taken by GPs once PDM is suspected. METHOD: A cross-sectional postal survey of a random sample of 300 GPs in New Zealand was undertaken. RESULTS: A 45.7% response rate was achieved. Approximately two-thirds of GPs (65.9%) had diagnosed at least one patient with a PDM problem in the last 12 months. Thirty percent of respondents indicated that they had been faced with at least one challenge in the past 12 months, with 'verbal threats' being the most common of these (16.3%). Benzodiazepines and opioids were identified as the most problematic drug classes. The action usually taken by the greatest number of GPs once they suspected PDM was to 'document it' (97.9%) followed closely by 'suggest an alternative drug' (96.7%) and 'refrain from prescribing the drug' (91.9%). DISCUSSION: PDM is an issue for GPs. The findings from this study have highlighted the need for further research into this concerning issue, specifically further quantification of the size of the problem in the New Zealand general population. There is also a need for the development and implementation of interventions to help minimise and better manage PDM in New Zealand. PMID- 22675695 TI - Gender differences in financial barriers to primary health care in New Zealand. AB - INTRODUCTION: Gender differences in health status and use of health care services have been established in the developed world with less attention paid to gender differences in financial barriers to primary care. Such barriers represent potentially avoidable mortality and morbidity. AIM: To examine gender differences in financial barriers to New Zealand primary health care. METHODS: Data from SoFIE-health, an add-on to Statistics New Zealand-led Survey of Family, Income and Employment (SoFIE), analysed using logistic regression, controlling for demographic, socioeconomic, health behaviour and health variables. Access to primary health care includes general practitioner and dental care and prescription drugs. RESULTS: Odds of deferring seeing their doctor(s), dentist and buying a prescription respectively at least once during preceding 12 months, because they could not afford the cost of a visit or prescription, were greater for women compared to men (Odds Ratio (OR) 1.82, 95% CI: 1.67-1.99; OR 2.05, 95% CI: 1.78-2.34; and OR 1.58, 95% CI: 1.47-1.71; respectively). Adjusting for demographic, socioeconomic, health behaviour and health status attenuated OR to 1.45 (1.31-1.61) for deferring medical visit, 1.47 (1.26-1.71) buying prescription, and 1.35 (1.24-1.46) for deferring dental visit, although confidence intervals still excluded the null. DISCUSSION: Gender significantly associated with reporting cost barriers to primary health care, regardless of individual deprivation or income levels, suggesting that primary health care policies targeting gender-specific factors are warranted. Policy measures to reduce co-payments may improve access to care for both women and men, and may have positive health implications. PMID- 22675696 TI - Access to general practice for Pacific peoples: a place for cultural competency. AB - INTRODUCTION: Access to primary health care services has been identified as a problem for Pacific peoples. Although cost is the most frequently cited barrier to Pacific service utilisation, some research has indicated that access may also be influenced by features of mainstream primary care services. This study aimed to identify features of mainstream general practice services that act as barriers to accessing these services for Pacific peoples in order to explore strategies that providers could adopt to enable their practices to be more welcoming, accessible and appropriate for Pacific peoples. METHODS: Pacific participants were recruited through Pacific networks known to Pegasus Health and via 'snowball' sampling. In total, 20 participants participated in one of three focus groups. A semi-structured interview explored the participants' views and experiences of mainstream general practice care. Thematic analysis was utilised to interpret the data. FINDINGS: The analysis revealed five themes highlighting non-financial features of mainstream general practice services that may influence the availability and acceptability of these services to Pacific peoples: language and communication; rushed consultations; appointment availability; reception; and Pacific presence. CONCLUSION: The findings indicate that all personnel within the primary care setting have the ability to directly engage in the improvement of the health status of Pacific peoples in New Zealand by developing cultural competency and incorporating flexibility and diversity into the care and service they provide. PMID- 22675697 TI - New Zealand pharmacists' experiences, practices and views regarding antibiotic use without prescription. AB - INTRODUCTION: Very few studies have investigated pharmacists' views, experiences and practices regarding the use of antibiotics without prescription. This study aimed to explore through self-report and hypothetical scenarios what factors determine New Zealand pharmacists' behaviour and attitudes towards non prescription use of antibiotics. METHODS: A purposeful sample of 35 registered community pharmacists of differing ethnic backgrounds was selected from a mixture of pharmacies that predominantly either serve New Zealand European customers or customers of other ethnicities. Semi-structured interviews including general background questions and six hypothetical scenarios were used for the investigation. Pharmacists' ethnicity, education, years of experience, and customers' ethnicity may influence their views, experiences and practices regarding the use of antibiotics without prescription. Customer demand or expectation, business orientation and competitiveness within community pharmacies, standards and practice of fellow pharmacists, ethics and professionalism, legislation, enforcement of the legislation, and apprehension of the consequences of such practice were hypothesised to have an effect on antibiotic use or supply without prescription by pharmacists. FINDINGS: The supply of antibiotics without prescription is not common practice in New Zealand. However, personal use of antibiotics without prescription by pharmacists may have been underestimated. Pharmacists were aware of legalities surrounding selling and using antibiotics and practised accordingly, yet many used antibiotics without prescription to treat themselves and/or spouses or partners. Many pharmacists also reported that under certain legislative, and regulatory and situational conditions they would sell antibiotics without a prescription. CONCLUSION: Views and practices regarding antibiotic use without prescription by community pharmacists require further exploration. PMID- 22675698 TI - Is our focus right? Workforce development for primary health care nursing. AB - INTRODUCTION: Effective workforce development is a key investment in producing quality health care. Service delivery stakeholders often assume that workforce development is best achieved through short clinical topic training or extended postgraduate courses; however, the views and preferences of primary health care (PHC) nurses have not routinely been sought. This study explores the workforce development needs of experienced PHC nurses in a provincial area of New Zealand. METHODS: In addition to a literature scan, two focus group interviews were held with nurses representing a broad range of PHC subspecialities. Participants also completed a brief survey regarding their own and colleagues' education needs. Nurse leaders in three District Health Boards (DHBs) and one Primary Health Organisation (PHO) were asked for comments on workforce strategies. Datasets were analysed separately then triangulated for overall themes. FINDINGS: Thirty-one PHC nurses attended the two focus groups. Participants noted changes to their roles in the last three years, including new areas of clinical and workforce development. Participants in both focus groups largely focused on structural and organisational barriers to PHC workforce development. CONCLUSIONS: PHC nurses have priorities for workforce development that may differ from stakeholders, and offering clinical education opportunities alone may not be enough. Providing leadership education as well as career mentoring appears to be as important as clinical education and should happen in conjunction with other workforce development opportunities. This research demonstrates a need for a nationally agreed education strategy for the PHC nursing workforce. PMID- 22675699 TI - Teamwork - general practitioners and practice nurses working together in New Zealand. AB - INTRODUCTION: Teamwork in primary health care has been encouraged in New Zealand and in the international literature. It may improve work satisfaction for staff, and satisfaction and outcomes for patients. Teamwork may be classified as being multi-, inter- or transdisciplinary and is likely to be influenced by the nature of the work and the organisational context. AIM: To describe and analyse teamwork between general practitioners and practice nurses in New Zealand. METHODS: Data were drawn from a survey of general practices and from interviews with primary health care staff and management. RESULTS: Doctors and nurses in general practice in New Zealand see themselves as a team. Evidence suggests that the nature of the work and the business context most often leads to a multidisciplinary style of teamwork. Some providers have adopted a more intense teamwork approach, often when serving more disadvantaged populations or in caring for those with chronic illnesses. DISCUSSION: Concepts of teamwork differ. This article provides a classification of teams and suggests that most general practice teams are multidisciplinary. It is hoped that this will help personnel to communicate their expectations of a team and encourage progressive team development where it would be of value. PMID- 22675700 TI - Adherence to evidence-based guidelines is the key to improved health outcomes for general practice patients: YES. PMID- 22675701 TI - Adherence to evidence-based guidelines is the key to improved health outcomes for general practice patients: NO. PMID- 22675702 TI - Pacific workforce development within primary health care. PMID- 22675703 TI - Guarana: Paullinia cupana, P. sorbilis; also known as Brazilian cocoa and 'zoom'. AB - The main constituent of guarana is caffeine, with smaller quantities of theophylline and theobromine. There is no evidence that the berries or extracts contain anything else that is therapeutically useful.Guarana is associated with many therapeutic properties, but there is no evidence to support these other than effects that can be attributed to caffeine. Guarana is widely available in herbal products and energy drinks. Excessive intake can cause the same effects as too much caffeine. It is not widely recognised that guarana has a high caffeine content and the labelling on some products is misleading.Although not specifically studied, guarana would be expected to exhibit the same range of adverse effects and drug interactions as those associated with caffeine. PMID- 22675704 TI - Diagnosis in primary care: probabilistic reasoning. PMID- 22675705 TI - Evidence does not support saturated fats being harmful for cardiovascular health. PMID- 22675706 TI - Contrast-enhanced ultrasonography for evaluating antiangiogenic treatment in hepatocellular carcinoma. A long way from research to clinical practice. PMID- 22675707 TI - Intermediate and advanced hepatocellular carcinoma treated with the antiangiogenic agent sorafenib. Evaluation with unenhanced and contrast-enhanced ultrasonography. AB - AIMS: To evaluate the sonographic changes observed in hepatocellular carcinoma (HCC) post antiangiogenic treatment with sorafenib. PATIENTS AND METHODS: Twenty one intermediate or advanced HCC patients (19 men, 2 women; mean age: 66.8 years; 32 target tumors-TTs) received sorafenib as monotherapy and were studied with unenhanced ultrasonography (US) and contrast-enhanced ultrasonography (CEUS) with a second generation echo-enhancer (SonoVue) at bimonthly intervals. Changes in lesional size, echotexture and enhancement were evaluated. Response was classified according to RECIST (Response Evaluation Criteria In Solid Tumors) and modified (m) RECIST. RESULTS: Cystic changes were detected on US in 4 patients (7 lesions); CEUS showed a significant (51-100%) decrease of viable, enhancing TTs in the aforementioned patients. Four additional patients (5 lesions) showed a 73 87% decrease of their viable TTs on CEUS, but no changes on US. 13/21 patients showed less than 30% decrease, no change, or increase of their viable TTs. Based on the last sonographic evaluation, response was as follows: RECIST- Complete Response, CR (n=0), Partial Response, PR (n=1), Stable Disease, SD (n=16), Progressive Disease, PD (n=4); mRECIST- CR (n=2), PR (n=6), SD (n=11), PD (n=2). The 8 responders (CR+PR) according to mRECIST had significantly longer mean overall survival (OS) compared to the 13 non-responders (21.5 vs 12.2 months, p=0.018, Kaplan-Meier method). However, statistical significance was reduced (p=0.065) after adjustment for BCLC and Child's class. CONCLUSION: US may occasionally detect changes indicative of the effect of sorafenib on HCC, but CEUS is required to evaluate and grade post-therapeutic reduction of tumoral enhancement. The latter is likely to correlate with OS. PMID- 22675708 TI - Contrast Enhanced Ultrasound for the evaluation of focal liver lesions in daily practice. A multicentre study. AB - BACKGROUND AND AIM: Development of contrast specific ultrasound techniques and introduction of the second-generation ultrasound contrast agents have improved the ability of this technique in detecting and characterizing focal liver lesions (FLLs). The purpose of this study was to present the experience of four Romanian centers in the evaluation of FLLs by contrast enhanced ultrasound (CEUS), in daily practice. MATERIALS AND METHODS: We performed a multicentre retrospective study, including 1244 FLLs, evaluated by means of CEUS in four Romanian centers with extensive experience in ultrasound, during September 2009-December 2010. RESULTS: This study included 1244 FLLs, both "de novo" (1056 cases) and pre existing (such as hepatocellular carcinomas evaluated after percutaneous treatment to assess the treatment results). In 1046/1244 of cases (84.1%), CEUS showed a typical pattern of enhancement (according to the EFSUMB Guidelines 2008), thus being sufficient for a correct and final diagnosis, while in 198/1244 of cases (15.9%), other methods of diagnosis were required, such as contrast CT/MRI or biopsy. In our study, CEUS established the benign or malignant nature of lesions in 1139/1244 of cases (91.5%). CONCLUSION: According to our results, CEUS could be the first imaging method of diagnosis for uncharacteristic FLLs detected by standard ultrasound, providing a correct classification in 84.1% of cases and a correct differentiation between benign/malignant lesions in 91.5% of cases. Thus, when faced with an uncharacteristic FLL on standard ultrasound, our local strategy is to perform CEUS as a first-line imaging investigation. PMID- 22675709 TI - Contrast-enhanced power Doppler endosonography and pathological assessment of vascularization in advanced gastric carcinomas--a feasibility study. AB - AIM: Besides representing angiogenesis markers, microvascular density (MVD) and vascular endothelial growth factor (VEGF) are two important tools for the assessment of prognosis in patients with gastric cancer. The aim of our study was to assess the Doppler parameters (resistivity and pulsatility indexes) and vascularity index (VI) calculated by contrast-enhanced power Doppler endoscopic ultrasound (CEPD-EUS) in correlation with the expression of intra-tumoral MVD and VEGF in patients with gastric cancer. MATERIAL AND METHODS: The study included 20 consecutive patients with advanced gastric carcinoma, but without distant metastasis at initial assessment. All the patients were assessed by contrast enhanced power Doppler endoscopic ultrasound (EUS) combined with pulsed Doppler examinations in the late venous phase. The vascularity index (VI) was calculated before and after injection of second generation microbubble contrast specific agent (SonoVue 2.4 mL), used as a Doppler signal enhancer. Moreover, pulsed Doppler parameters (resistivity and pulsatility indexes) were further calculated. The correlation between power Doppler parameters and pathological/molecular parameters (MVD assessed through immunohistochemistry with CD31 and CD34, as well as VEGF assessed through real-time PCR) was assessed. Kaplan-Meier survival analysis was used for the assessment of prognosis. RESULTS: Significantly statistical correlations were found between post-contrast VI and CD34 (p=0.0226), VEGF (p=0.0231), VEGF-A (p=0.0464) and VEGF-B (p=0.0022) while pre-contrast VI was correlated only with CD34 expression. Pulsatility index and resistivity index were not correlated with MVD or VEGF expression. Survival analysis demonstrated that VEGF-A is an accurate parameter for survival rate (p=0.045), as compared to VEGF (p=0.085) and VEGF-B (p=0.230). We did not find any correlation between the survival rate and ultrasound parameters (RI, PI, pre-contrast VI or post-contrast VI). CONCLUSION: Assessment of tumor vascularity using contrast-enhanced EUS, including analysis of spectral Doppler parameters is possible and feasible in gastric cancer patients. A correlation between measured EUS vascularity and pathological parameters of angiogenesis (MVD and VEGF expression) was found. PMID- 22675710 TI - Added value of intravenous contrast-enhanced ultrasound for characterization of cystic pancreatic masses: a prospective study on 37 patients. AB - The aim of this study was to evaluate the added value of contrast-enhanced ultrasound (CEUS) in the pancreatic cystic mass (PCM) diagnosis by using a qualitative and quantitative analysis in order to make a relevant characterization. PATIENTS AND METHOD: Between December 2008 and November 2011, 37 patients with PCM discovered at ultrasound examination were prospectively followed. A qualitative and quantitative CEUS analysis was performed in order to differentiate etiologies of the PCM. In the quantitative analysis several parameters were followed: Peak Intensity (PI), Time to Peak (TTP), maximum ascending gradient (GRAD), Time to maximum gradient (TTG) and Area Under the Curve (AUC). Normalized ratios were also calculated. In all patients a definite cytological or histological diagnosis was obtained. RESULTS: Thirty-seven patients were studied: 12 with pancreatitis-associated pseudocyst and 25 with cystic tumors (10 serous cystic adenoma, 5 mucinous cystic adenoma, 6 cystadenocarcinomas, 2 solid pseudopapillary tumors and 2 intraductal papillary mucinous neoplasms). There was a significant difference of the nAUC and nTTP between pseudocyst and cystic tumors, p=0.03 and p=0.01, respectively. A normalized TTP value above 7 sec was suggestive for the diagnosis of pseudocysts with 79.16 % accuracy. There was a significant difference of nTTP and nTTG between the benign and malignant lesions. nTTP < 9 sec and nTTG < 8.5 sec rules out malignant cysts in almost 90% of cases. CONCLUSION: The CEUS is useful in the diagnosis of PCM. The quantitative analysis of the enhancement of the cystic wall may discriminate the different types of the PCM. PMID- 22675712 TI - Teaching basic shoulder ultrasonography to orthopaedic postgraduate trainees- effectiveness of a training workshop. AB - AIM: Ultrasound examination of the shoulder conducted by orthopaedic surgeons in the diagnosis and treatment of shoulder conditions is increasingly reported. Shoulder ultrasound is not a mandatory component of postgraduate orthopaedic training in the United Kingdom. The aim of this study was to assess the effectiveness of the shoulder ultrasound teaching workshop administered to postgraduate orthopaedic surgical trainees. METHODS: Orthopaedic trainees participated in a teaching workshop on shoulder ultrasound examination with particular emphasis on demonstrating the Acromioclavicluar joint (ACJ) and the long head of the biceps (LHB) in the biciptal groove. The ability of the trainees to demonstrate the ACJ and the LHB using ultrasound was then assessed. RESULTS: Thirty three orthopaedic trainees participated in this study. Twenty three (70%) trainees were able to demonstrate the ACJ and 14 (42%) trainees were able to demonstrate the LHB without assistance, following the ultrasound teaching workshop. The skills acquired by the trainees were independent to the year in training and previous shoulder experience (p > 0.05). CONCLUSION: Our study shows that a basic shoulder ultrasound teaching workshop can be effective in equipping postgraduate orthopaedic trainees with basic ultrasound techniques. It could potentially become part of a structured orthopaedic training programme. PMID- 22675711 TI - Intrathoracic tumors in contact with the chest wall--ultrasonographic and computed tomography comparative evaluation. AB - AIM: A comparative evaluation of lung lesions in contact with the thoracic wall by transthoracic ultrasonography (US) and computed tomography (CT). MATERIAL AND METHOD: A retrospective analysis of the US and CT results was performed in 131 patients with thoracic masses. In all of these cases the histological diagnosis was established after a US guided transthoracic biopsy. A comparative analysis of the two methods was realized regarding the following items: lesion dimensions, presence of tumoral wall invasion, peritumoral atelectasis, presence of pleural effusion and incidence of post-biopsy complications. RESULTS: A number of 17 patients from the study group were diagnosed with benign lesions and 114 (87%) with malignancies. US showed signs of wall invasion in 78 patients (68.42%), whereas CT revealed it in 83 of the patients (72.8%) from the malignancies group. Intratumoral necrosis was diagnosed by US in 100 patients (87.71%) and by CT in 83 patients (72,8%), also from the 114 patients with malignant lesions. US found peritumoral atelectasis in 33 cases and CT in 38 cases. All parameters had good and very good correlation indexes between the methods (kappa = 0,8; 0,6; 0,72; p < 0,001 in all cases). CONCLUSIONS: In patients with thoracic masses in contact with the thoracic wall there is an overlap in the diagnosis performances of US and CT. The sensitivity and specificity of US in diagnosing wall invasion of malignant lesions is superior to that of CT. PMID- 22675713 TI - The role of Doppler indices in predicting intra ventricular hemorrhage and perinatal mortality in fetal growth restriction. AB - OBJECTIVES: The aim of this study is to determine whether Doppler indices predict intra-ventricular hemorrhage and perinatal mortality in fetal growth restricted pregnancies (FGR). MATERIAL AND METHODS: In this cohort study, 43 FGR fetuses underwent multi-vessel Doppler ultrasounds weekly or twice weekly after admission. Blood gases of the umbilical cord were analyzed immediately after delivery. Ultrasonography of the neonatal brain was performed after birth. Intra ventricular hemorrhage (IVH) and perinatal mortality were studied as outcomes. RESULTS: The median gestational age at the diagnosis of fetal growth restriction was 31 weeks, and the median age at delivery was 33.4 weeks. Seven cases had IVH. The chance of IVH was about five times greater in cases of absent/reversed umbilical diastolic flow (AREDF). The predicting factors for IVH were gestational age at delivery, birth weight, and acidosis. Nine neonates died in the neonatal period. AREDF, the Resistance Index of middle cranial artery (MCA/RI) and umbilical artery (UA), and absent/reversed "a" waves in ductus venosus (DV) were the Doppler indices predicting perinatal mortality. The other prognostic factors for perinatal mortality were gestational age at diagnosis and delivery, final amniotic fluid, Apgar score, and acidosis. CONCLUSION: Doppler indices, such as AREDF, can be predictors of IVH or perinatal death, and an absent or reversed "a" wave in the ductus venosus and the hypoxic index can be significant predictors of death in fetuses with fetal growth restriction. However, other important factors for IVH were gestational age at delivery and birth weight. The most important factors predicting perinatal mortality were gestational age, birth weight, acidosis, low AF, and low Apgar score. PMID- 22675714 TI - Ultrasound of the shoulder. AB - Ultrasonography (US) is a helpful imaging tool in the evaluation of the musculoskeletal system. It has some advantages over the other imaging techniques, such as plain radiography, computed tomography and magnetic resonance imaging, represented by the non-invasiveness and multiplanar imaging capability, repeatability, lack of radiation burden, good patient acceptance, and relatively limited costs. US offers an excellent resolution and a possibility for real-time dynamic examination of the joints and surrounding soft tissues, as well as enables monitoring of therapeutic response. The most common clinical indications for US examination of the shoulder are rotator cuff and biceps tendon pathology (tenosynovitis, tendinosis, complete and partial tears, and impingement) and disorders of other soft-tissue structures (joint recesses, bursae, muscles, suprascapular and axillary nerves) as well as bony cortex abnormalities. US is very useful for US-guided procedures (biopsy, joint and bursae aspirations and injections, aspiration and dissolution of calcific tendinosis). The aim of this article is to analyze the current literature about US of the shoulder and to describe both normal and pathological findings. PMID- 22675715 TI - Ultrasound assessment of the elbow. AB - Ultrasonography of the elbow is a very helpful and reliable diagnostic procedure for a broad spectrum of rheumatic and orthopedic conditions, representing a possible substitute to magnetic resonance imaging for evaluation of soft tissues of the elbow. Musculoskeletal ultrasound (US) shows many advantages over other imaging modalities, probably the most important being its capability to perform a dynamic assessment of musculoskeletal elements with patient's partnership and observation during examination. In addition, ultrasonography is cost effective, easy available, and has excellent and multiplanar capability to visualize superficial soft tissue structures. Among all imaging procedures, US is highly accepted by patients. US assessment of the elbow requires good operator experience in the assessment of normal anatomy, and suitable high-quality equipment. US of the elbow provides detailed information including joint effusions, medial and lateral epicondylitis, tears of the distal biceps and triceps tendons, radial and ulnar collateral ligament tears, ulnar nerve entrapment, cubital or olecranon bursitis and intra-articular loose bodies. The aim of this paper is to review the screening technique and the basic normal and pathological findings in elbow US. PMID- 22675716 TI - Prenatal ultrasound diagnosis of neural tube defects. Pictorial essay. AB - Neural tube defects (NTD) are a heterogeneous group of malformations resulting from failure of normal neural tube closure before the fourth and fifth week of embryologic development. The three most common forms of NTD are: anencephaly, encephalocele and spinal dysraphism. Less common forms of neural tube defects include iniencephaly, amniotic bands and other types of spinal abnormalities including scoliosis/cyphosis, sacral agenesis, limb-body wall complex, diastematomyelia. The most part of these abnormalities are accessible to the ultrasound diagnosis in the midtrimester and sometimes even in the late first trimester of the pregnancy. This kind of abnormalities can occur in isolation or in association with other anomalies, which can also be characterized with ultrasound. In this pictorial essay the ultrasonographic aspects of the NTD will be discussed. PMID- 22675717 TI - Ultrasonographic diagnosis of median arcuate ligament syndrome: a report of two cases. AB - The compression of the proximal part of the celiac trunk by median arcuate ligament of the diaphragm during expiration is defined as median arcuate ligament syndrome. It is a rare cause of chronic mesenteric ischemia. We report two cases with this syndrome, primarily diagnosed by Doppler ultrasound. The diagnosis was confirmed with digital substraction and computed tomography angiography in both cases. The role of ultrasound in the diagnostic work up of this syndrome is discussed with regard to the recent literature. PMID- 22675718 TI - Scrotal migration of a ventriculoperitoneal shunt: a case report and review of literature. AB - Ventriculoperitoneal (VP) shunt insertion may be associated with migration into the abdominal wall, gastrointestinal tract, bladder, vagina, scrotum, and mediastinum. Migration of the VP shunt into the scrotum has been rarely reported. We present a 1 year old boy with cerebrospinal fluid hydrocele due to the migration of a VP shunt catheter into the right side scrotum. PMID- 22675719 TI - Real-Time 3D echocardiography in a young adult with idiopathic dilatation of the pulmonary artery: a case report. AB - Idiopathic dilatation of the pulmonary artery (IDPA) is an uncommon anomaly occurring in 0.6% of patients with congenital heart disease. IDPA is characterized by the enlargement of the main pulmonary artery with or without dilatation of the right and left pulmonary arteries. We describe 2D and Real-Time 3D Echocardiography findings in a young adult with IDPA. To the best of our knowledge this is the first case reporting all echocardiographic findings diagnostic for IDPA. PMID- 22675720 TI - Appendicitis associated with intestinal malrotation: imaging diagnosis features. Case report. AB - Intestinal malrotation is a rare pathological situation consisting of non rotation or incomplete rotation of the primitive intestine. Due to the abnormal caecal position inflicted by malrotation, diagnosis of acute appendicitis is difficult. Ultrasonography (US) and Computed Tomography (CT) are relevant and complementary imaging techniques for establishing an otherwise elusive diagnosis. We present the case of 54 year old male presenting with nonspecific abdominal complaints in which US (standard and contrast enhanced) and CT scans identified acute appendicitis associated with malrotated caecum and ascending colon, located in the left hipocondrum. PMID- 22675721 TI - Recurrent pain and swelling of the right forearm in a 34 year-old patient. PMID- 22675722 TI - Cystic tumor of the liver. PMID- 22675724 TI - Should I ever fix a clavicular fracture? Commentary on an article by Robbin C. McKee, et al.: "Operative versus nonoperative care of displaced midshaft clavicular fractures: a meta-analysis of randomized clinical trials". PMID- 22675725 TI - What HIV-positive young women want from behavioral interventions: a qualitative approach. AB - Young women living with HIV in the United States face many social and psychological challenges, including involvement in health care and secondary prevention efforts. The factors that put these young women at risk for HIV acquisition initially, such as poverty, gender roles, cultural norms, and limited perceived control over sexual relationships, continue to place them at risk for both adverse mental and physical health outcomes that impact their daily lives and secondary prevention efforts. This study utilized focus groups with young HIV positive women in order to better understand their perceived problems and pressures and to inform a developmentally appropriate secondary prevention intervention for young HIV-positive women that could be implemented in clinical care settings. Focus groups with young HIV-positive women were convened in three U.S. cities: Baltimore, Chicago, and Tampa. A total of 17 young, HIV-positive women, age range 17-24 (mean age=21), participated in the focus groups. This article describes the psychological and social challenges these young women face as well as their suggestions regarding secondary HIV prevention intervention components. PMID- 22675726 TI - Prediction models for early risk detection of cardiovascular event. AB - Cardiovascular disease (CVD) is the major cause of death globally. More people die of CVDs each year than from any other disease. Over 80% of CVD deaths occur in low and middle income countries and occur almost equally in male and female. In this paper, different computational models based on Bayesian Networks, Multilayer Perceptron,Radial Basis Function and Logistic Regression methods are presented to predict early risk detection of the cardiovascular event. A total of 929 (626 male and 303 female) heart attack data are used to construct the models.The models are tested using combined as well as separate male and female data. Among the models used, it is found that the Multilayer Perceptron model yields the best accuracy result. PMID- 22675727 TI - A roadmap for regenerative medicine. PMID- 22675728 TI - Ottoline Leyser. PMID- 22675729 TI - Pappenheimer bodies in a splenectomized patient with alcohol abuse. PMID- 22675730 TI - Electroconvulsive seizures regulates the Brd1 gene in the frontal cortex and hippocampus of the adult rat. AB - Depressive disorders represent a significant health concern as they are associated with high social and physical dysfunction and increased risk for suicide. Electroconvulsive therapy (ECT) is the most effective treatment for patients with drug-resistant severe depressive disorders. However, the underlying biological mechanisms of ECT are not well characterized. In particular, the regulation of transcription factors upon ECT has only just started to be unveiled. The schizophrenia and bipolar disorder associated bromodomain containing 1 (BRD1) gene is important for the acetylation of histone H3K14 and holds a key role in normal embryonic development and survival. In this study, we have measured Brd1 mRNA in the hippocampus and the frontal cortex of male Sprague Dawley rats upon acute and repeated electroconvulsive seizures (ECS) over a period of 10 days. We found an increase in the general expression of Brd1 mRNA in the hippocampus after repeated ECS compared to sham (F = 8.108, P = 0.003). Furthermore, we provide evidence suggesting a decrease in the expression of the Brd1 mRNA variant comprising an extended version of exon 7 (Brd1-L) in the frontal cortex after repeated ECS compared to sham (F = 6.225, P = 0.023). These findings indicate that regulation of the Brd1 gene is part of the biological response to ECS and that splice variants are induced differentially in different brain regions. PMID- 22675732 TI - States trim what they can to restrain Medicaid costs. PMID- 22675731 TI - Tetraoxanes: synthetic and medicinal chemistry perspective. AB - The discovery of artemisinin from Chinese medicinal plant, Artemisia annua in 1971, opened a new era in the malarial chemotherapy. This discovery was the beginning of exploring peroxides as potential replacements for the traditional antimalarial drugs such as chloroquine and mefloquine. The structurally simple class of peroxides that emerged from these studies was the 1,2,4,5-tetraoxanes. This study describes the current status of tetraoxane-based antimalarials that show significant promises because of their artemisinin-like activity. Literature from 1999 has been critically reviewed and an attempt has been made to discuss various synthetic methods and structure-activity relationship study among the series of tetraoxane-based compounds. PMID- 22675733 TI - CMS prepares to tie Medicare physician pay to performance. PMID- 22675734 TI - Largest domestic health plans building overseas operations. PMID- 22675735 TI - Greater scrutiny of internally collected data needed. PMID- 22675736 TI - Employer-sponsored insurance here to stay. PMID- 22675747 TI - [Inflammatory enteric diseases and carcinogenesis]. PMID- 22675749 TI - [Chronic hepatitis and liver cancer]. PMID- 22675748 TI - [Effects of MSCs on the progression of atherosclerosis plaque in ApoE-knock out mice]. AB - AIM: To explore the effects of mesenchymal stem cells in the formation of atherosclerosis plaque in hypercholesterolemic apoliprotein (apo) E -/ - mice. METH-ODS: ApoE -- mice mesenchymal stem cells (MSCs)were isolated and identified. Thirty ApoE -/ - mice were divided into negative control group (Neg, n = 10), positive control group (Pos, n = 10) and MSCs group ( n = 10).MSCs were injected through caudal vein into the body ofPos and MSCs groups. The plaque area of all subjects were compared, the percentage of CD4 CD25' regulatory T cells in different tissues were analyzed by FACS, proliferation response of splenocytes to mesenchymal stem cells and cyto-kines in the supernatant were determined by ELISA. RE-SULTS: Compared with controls, MSCs resulted in a significant decrease of the atherosclerotic plaques size (P <0.05), and a significant increase of CD4 CD25 regulatory T cells in spleen (P<0.05). Specific proliferation response of CD4' CD25' regulatory T cells in splenocytes to MSCswas significantly suppressed. The supernatant levels ofTGF-f3 and IL-10 in MSCs group were increased while IFN y decreased significantly. CONCLUSION: MSCs play an important role in regulating the inflammatory response and may significantly inhibit the formation of the atherosclerosis plaque in ApoE-'- mice. PMID- 22675750 TI - [Approach to the treatment of asthma as a chronic inflammation]. PMID- 22675751 TI - [Early diagnosis and new diagnostic methods for rheumatoid arthritis]. PMID- 22675752 TI - [Coronary artery disease and inflammation]. PMID- 22675753 TI - [Chronic kidney disease--understanding as a systemic disease]. PMID- 22675754 TI - [Inflammation and peripheral nerve diseases (on immunologic peripheral nerve dysfunctions)]. PMID- 22675755 TI - [Etiology and treatment of fulminant hepatitis]. PMID- 22675756 TI - [Diagnosis and treatment of chronic pancreatitis]. PMID- 22675757 TI - [Diagnosis and treatment of thyrotoxicosis]. PMID- 22675758 TI - [Metabolic syndrome--its relationship with carbohydrate metabolism disorders]. PMID- 22675759 TI - [Therapy and prevention of cardiogenic cerebral embolism]. PMID- 22675760 TI - [Current trend in prion disease in man]. PMID- 22675761 TI - [Treatment of collagen diseases. Clinical application of immunosuppressive agents]. PMID- 22675762 TI - [Physiopathology and therapeutic approach to auricular fibrillation]. PMID- 22675764 TI - [Diagnosis and treatment of interstitial pneumonia]. PMID- 22675763 TI - [Metabolic syndrome and cardiovascular diseases]. PMID- 22675765 TI - [Physiopathology and treatment of bronchial asthma]. PMID- 22675766 TI - [New disease concept: chronic kidney disease (CKD)]. PMID- 22675767 TI - [Physiopathology and treatment of diabetic nephropathy]. PMID- 22675768 TI - [Diagnosis and treatment of leukemia]. PMID- 22675769 TI - [Diagnosis and treatment of myelodysplastic syndrome]. PMID- 22675770 TI - [Current topics on newly discovered infections such as avian influenza]. PMID- 22675771 TI - [Establishment of the classification for severity of illness of nosocomial pneumonias based on the analysis of their actual conditions]. PMID- 22675772 TI - [Diagnosis of nosocomial pneumonias and the microbiological tests for the causative pathogens]. PMID- 22675773 TI - [Basic concept in the selection of antibiotics for treatment of nosocomial pneumonias]. PMID- 22675774 TI - [Evaluation of efficacy and duration of drug therapies for patients with nosocomial pneumonia]. PMID- 22675775 TI - [Countermeasures for patients with nosocomial pneumonia who do not respond to therapies]. PMID- 22675776 TI - [Pneumonia in patients with immunodeficiency]. PMID- 22675777 TI - [Ventilator-associated pneumonia]. PMID- 22675778 TI - [Aspiration pneumonia]. PMID- 22675779 TI - [Supportive therapy for patients with nosocomial pneumonia using immunoglobulin and steroids]. PMID- 22675780 TI - [Administration of antibiotics for treatment of nosocomial pneumonia in elderly patients or patients with kidney dysfunction]. PMID- 22675781 TI - Hippos help shed light on photoprotection. PMID- 22675782 TI - International Conference on Harmonisation; guidance on S2(R1) Genotoxicity Testing and Data Interpretation for Pharmaceuticals intended for Human Use; availability. Notice. AB - The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled ''S2(R1) Genotoxicity Testing and Data Interpretation for Pharmaceuticals Intended for Human Use'' (ICH S2(R1)). This guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The ICH S2(R1) combines and replaces two ICH guidances, "S2A Specific Aspects for Regulatory Genotoxicity Tests for Pharmaceuticals'' and "S2B Genotoxicity: A Standard Battery for Genotoxicity Testing of Pharmaceuticals.'' ICH S2(R1) provides guidance to drug sponsors on which tests should be performed to assess potential genotoxicity of pharmaceuticals. It also provides guidance on testing conditions, data interpretation, and followup strategies if a positive response is seen in in vitro assays. This guidance is intended to provide drug sponsors with recommendations to ensure that drugs are appropriately tested for potential to cause genetic damage and to ensure efficient development of new drugs. PMID- 22675783 TI - Is Missouri going to pot? Reefer madness: legal or medical marijuana! PMID- 22675784 TI - Legalization, decriminalization & medicinal use of cannabis: a scientific and public health perspective. AB - Empirical and clinical studies clearly demonstrate significant adverse effects of cannabis smoking on physical and mental health as well as its interference with social and occupational functioning. These negative data far outweigh a few documented benefits for a limited set of medical indications, for which safe and effective alternative treatments are readily available. If there is any medical role for cannabinoid drugs, it lies with chemically defined compounds, not with unprocessed cannabis plant. Legalization or medical use of smoked cannabis is likely to impose significant public health risks, including an increased risk of schizophrenia, psychosis, and other forms of substance use disorders. PMID- 22675785 TI - The use of marijuana to treat glaucoma. PMID- 22675786 TI - Part II--drug shortages: Big pharma's new business model. PMID- 22675787 TI - Health care fraud & the FBI. PMID- 22675788 TI - Advocate for immunizations. PMID- 22675789 TI - Saint Louis University Internal Medicine celebrates 100 years of excellence. PMID- 22675790 TI - The history of the Department of Internal Medicine at Saint Louis University. AB - The Department of Internal Medicine at Saint Louis University has a long and proud tradition of excellence in patient care, research and education that goes back for 100 years, but also appears to remain strong for the future. The department has played a key role in several medical discoveries and innovations over the last 100 years and continues to make an impact on those in its community. PMID- 22675791 TI - A century of influenza prevention in St. Louis. AB - The 1918 pandemic of influenza in St. Louis was ameliorated by the public health efforts of the City Health Department. At the time, St. Louis was the sixth largest city in the US; among the ten largest cities, St. Louis had the fewest influenza cases and deaths. Closing schools, churches, theaters, and other public meeting places reduced the severity of the pandemic in St. Louis. The benefits of contemporary influenza vaccines to prevent influenza and economic disruption are summarized. PMID- 22675792 TI - Vitamin D and the kidney. AB - In the course of chronic kidney disease, alterations in vitamin D metabolism contribute to increases in the levels of parathyroid hormone and the development of skeletal disorders, and in addition, may contribute to hypertension, systemic inflammation and cardiovascular risk. In the course of chronic kidney disease, the production of 1,25-dihydroxyvitamin D from the kidney shows a progressive decline due to several factors, which include a reduction in the ability to convert 25-hydroxyvitamin-D to the active hormone, 1,25-dihydroxyvitamin D. The resulting 1,25-dihydroxyvitamin D, as well as 25-hydroxyvitamin D deficiency, correlates strongly with accelerated disease progression and mortality. An understanding of the pathophysiology involved leads to therapeutic strategies to correct these abnormalities, with the ultimate view to improve outcomes for patients with CKD. PMID- 22675793 TI - Latest in cystic fibrosis. AB - Cystic Fibrosis (CF) is a genetic disease affecting multiple organs. There are about 30,000 patients with CF in the United States, resulting from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, as well as its protein product. The life expectancy of CF patients has increased steadily over recent years, with the current expectation being for them to live into their late 30s. This is due to increased understanding, and therapeutic advances in the CF treatment armamentarium. PMID- 22675794 TI - Hemochromatosis: discovery of the HFE gene. AB - Hereditary hemochromatosis (HH) is a common inherited disorder of iron metabolism affecting about 1 in 250 individuals. HH results in an increased absorption of iron at the baso-lateral surface of the enterocyte with aberrant regulation of ferroportin-mediated transfer of iron in turn brought on by a decrease in circulating hepcidin. The medical literature describes a colorful history of HH with important contributions from faculty at Saint Louis University. PMID- 22675795 TI - Update in the management of coronary artery disease. AB - We review several approaches that represent contemporary coronary disease management including noninvasive coronary imaging, selection of patients for revascularization, assessment of coronary lesions for physiologic significance and vulnerability to future ischemic events, and strategies to improve the safety of revascularization procedures. Better understanding of the pathophysiology of atherosclerosis has made secondary prevention therapies among patients with established coronary disease the highest priority, and we also discuss this evolution. PMID- 22675796 TI - Fish oil supplementation & coronary artery disease: does it help? AB - Omega-3 polyunsaturated fatty acids (PUFAs) have been shown to decrease the risk of cardiovascular disease. They reduce fatal and non-fatal myocardial infarction, stroke, coronary artery disease (CAD), sudden cardiac death, and all-cause mortality. They are well tolerated and cause minimal adverse effects. In this review, we sought to provide an overview of the current literature on the use of Omega-3 fatty acids for the treatment of CAD and discuss the possible benefits. PMID- 22675797 TI - Dabigatran: a new anticoagulant for stroke prevention in patients with atrial fibrillation. AB - Ischemic stroke is arguably the most feared complication of atrial fibrillation. While warfarin has been the most effective pharmacologic treatment for stroke prevention in patients with nonvalvular atrial fibrillation, several limitations have led to its underutilization. Recently, dabigatran (Pradaxa), a new oral anticoagulant with several potential advantages over warfarin (Coumadin), became available for use in the United States for prevention of stroke and systemic embolism in patient with nonvalvular atrial fibrillation. PMID- 22675798 TI - Simplified evaluation of the jugular venous pressure: significance of inspiratory collapse of jugular veins. AB - The evaluation of the jugular venous pulse (JVP) remains one of the most important elements of the physical examination. Unfortunately, the examination remains difficult for most clinicians since traditional methodology is not commonly used or understood. Echocardiography has shown that the right atrial pressure can accurately be predicted as normal by observing a 50% inspiratory collapse of the inferior vena cava. We have adapted this finding to the clinical examination and experience has shown that if the jugular vein collapses during deep inspiration that both the right atrial pressure and the JVP are normal. We propose that this finding, which is easily detected in most patients, be incorporated as a standard observation in the assessment of the JVP. Thus, when evaluated in the supine position, distended neck veins that do not collapse indicate an abnormally elevated venous pressure, while visible veins that collapse during deep inspiration or with a vigorous sniff suggest a normal JVP, and those that are not (or barely) visible that collapse indicate a low JVP. This methodology is applicable to most clinical situations. PMID- 22675799 TI - Prenatal counseling's effect on rates of neonatal intensive care admission for feeding problems cleft lip/palate infants. AB - Prenatal counseling and feeding instruction is standard at our institution for parents of cleft lip and palate patients. We studied this intervention's effect on Neonatal Intensive Care Unit (NICU) admission solely for feeding. Ten percent (2/20) of patients whose parents received counseling were admitted to the NICU for feeding issues alone compared to 21% (5/24) of the non-counseling group. Prenatal counseling and feeding instruction appears to decrease NICU admission, duration and health care costs. PMID- 22675800 TI - Findings from the Pacific Islands Families Study. PMID- 22675801 TI - Cohort profile: a decade on and strong--the Pacific Islands Families Study. PMID- 22675802 TI - What defines 'low birth weight' in Pacific infants born in New Zealand? AB - AIM: To report the combined and ethnic specific proportions of preterm and low birth weight (LBW) births, and average birth weights, for New Zealand's four major Pacific ethnic groups (Samoan, Tongan, Cook Island Maori, Niuean). METHODS: Data were gathered from the Pacific Island Families Study (PIFS). Mothers of a cohort of 1398 Pacific infants born in South Auckland New Zealand (NZ) during 2000 were interviewed when their infants were 6 weeks old. Birth outcome data were obtained from hospital records on receipt of full informed consent. RESULTS: Of the Pacific ethnic groups preterm rates ranged from 5.3% to 8.3% (7.3% overall), LBW rates ranged from 3.4% to 5.7% (4.0% overall), and average birth weight of full-term deliveries ranged from 3467 gm to 3751 gm (3664 gm overall). Cook Island and Niuean infants were significantly lighter than Samoan infants. Infants of Pacific born mothers were significantly heavier than infants born to NZ born Pacific mothers. There were no differences observed between infants of 'ethnically homogenous' parents compared 'ethnically heterogeneous' parents. The 10th percentile for all Pacific ethnic groups ranged from 2894 to 3065 grams. CONCLUSION: These data reaffirm that infants of various Pacific ethnic groups are larger than other New Zealand infants. Furthermore, analyses of the PIFS cohort suggest that a LBW threshold for NZ born Pacific infants of 3000 grams may be more appropriate. PMID- 22675803 TI - Parental perceptions of their child's weight and future concern: the Pacific Islands Families Study. AB - AIM: Little is known about the perception of overweight, expressed as a level of concern, of Pacific parents and its relevance to children's weight. The aim of this study was to analyse data collected at birth and four and six years in the Pacific Island Families Study (PIFS) to investigate the relationship between parental perceptions of child weight status and actual weight status. METHOD: A total of 569 parent child dyads (299 boys (52.5%), 270 girls (47.5%); 47.1% Samoan, 20.9% Tongan, 18.6% Cook Island, 4.9% Niue, 8.4% other Pacific) were examined in this Parental Perception of Overweight Obesity Study (PPOS). At four and six years the question was asked of the parent "How concerned are you about your child becoming overweight?" A 5-point Likert scale was used, with possible answers ranging from "unconcerned" through increasing levels of concern to "very concerned". At four and six years weight and height were also measured and body mass index (BMI) derived and classified using international standards. Potential factors associated with parental perception were examined in a multivariate model using logistic regression. RESULTS: The majority of parents were unconcerned at four and six years (62% and 69.1%) about the future overweight status of their child. Using the international BMI classifications, at four years 40.1% of the children were classified as normal weight, 34.1% as overweight, and 25.8% as obese. At six years the proportions were similar; i.e., normal 41.3%, overweight 31.1%, and obese 27.6%. At four and six years the proportion of parents who were concerned about their child's future weight status was related to the child weight status e.g., at 6 years 20% of parents of normal children, 28% percent of parents of overweight and 51% of parents of obese children were concerned (p trend < 0.0001). Ethnicity and parity were significantly related to parental perceptions (p < 0.0001); identification with Tongan ethnicity was related to a higher proportion of concerned parents and an increased number of children in the family were related to a smaller proportion of concerned parents. DISCUSSION: While the level of concern was low and the prevalence of overweight and obesity high, the context of the socio economic and demographic environments must be taken into account in the formulation of interventions. Overweight and obese Pacific children may benefit from interventions that target the awareness of parents, making them more conscious of the relationship of obesity with food and activity patterns and give practical support to change the environment. These findings raise the concern that there is a normalisation of overweight and obesity in Pacific parents and/or children. Interventions firstly should address the socio economic demographic environment of a Pacific family making healthier choices the easier choices. PMID- 22675804 TI - Child developmental assessment at two-years of age: data from the Pacific Islands Families Study. AB - AIMS: To describe the developmental profile of Pacific children living in New Zealand at two years of age in personal/social, language, cognitive, fine motor, and gross motor domains, and to examine how sociodemographic, maternal, and cultural factors influence children's development. METHODS: A cohort of Pacific infants born during 2000 in Auckland, New Zealand, was followed up at two-years postpartum. Maternal interviews were administered and the developmental status of the child was measured using the Australian Developmental Screening Test. RESULTS: Maternal child development reports are presented for 1,018 two-year-old children. The majority of children were identified as having no developmental delay. The prevalence of no delay in any of these five domains was 64.8%. For those children (35%) who were identified with possible overall delay the significant risk factors were child ethnicity, low birth weight, being breastfed for less than six weeks, and single parenthood. DISCUSSION: The powerful associations of these factors and developmental outcome suggest that interventions need to have the flexibility to address such issues within individual Pacific families and communities. PMID- 22675805 TI - Agreement and discordance of parents' and teachers' reports of behavioural problems among Pacific children living in New Zealand. AB - Research suggests that ratings of child psychopathology by parents and teachers are generally not highly correlated. We examined the agreement and discordance between the child behaviour ratings of parents and teachers of a cohort of 6-year old Pacific children living in New Zealand, based on scores from the Child Behaviour Checklist and the Teacher Report Form. Mother's reports were obtained for 1019 children, of whom, 602 also had father's reports and 559 had teacher's reports. Rater agreement was low between all pairs of informants. Fathers and teachers had higher agreement than mothers and fathers, the latter in turn had higher agreement than mothers and teachers, and agreement was generally higher for Externalizing problems than Internalizing problems. In terms of discordance, mothers reported more aggressive behaviour than fathers, while fathers reported more Internalizing and Total problems than mothers. Mothers and fathers generally reported more behaviour problems than teachers. The higher agreement found between informants from different settings (fathers and teachers) than between informants from similar settings (mothers and fathers) is in contrast with some of the literature. Further research is needed to investigate how child, informant, and setting characteristics affect ratings of children's behaviour. PMID- 22675806 TI - Traditional gift-giving and gambling amongst Pacific mothers living in New Zealand. AB - Cultural variables are implicated in gambling literature as playing an important role in the initiation and maintenance of gambling activity, however there remains a paucity of research that defines and investigates the association between cultural factors, gambling and problem gambling amongst different cultural groups. The first data collection point for a cohort of mothers within the longitudinal Pacific Islands Families study identified that the Pacific cultural practice of traditional gift-giving was associated with gambling activity and expenditure. In this paper, data about traditional gift-giving and gambling are presented from the third collection point within this study. The results support an association between gambling (rather than problem gambling) and traditional gift-giving. This paper contends the need to contextualise Pacific peoples gambling within Pacific cultures. Also a need is identified to examine and address the psycho-social and cultural impacts of gambling for Pacific peoples. PMID- 22675808 TI - Utilisation of Traditional Pacific Healers by mothers and children of the Pacific Islands Families Study. AB - AIM: This research explores data on the mother's willingness to use, and children's use of Traditional Pacific Healers (TPH) from the first five waves of the Pacific Islands Families study (PIFS). Specific aims were: to report the prevalence of, and describe factors associated with, (1) the willingness of Pacific mothers to use the health services of Traditional Pacific Healers, (2) the use of Traditional Pacific Healers to treat children within the cohort and (3) to assess whether the use of Traditional Pacific Healers was a substitute or a supplement for western medicine. METHODS: Mothers were asked whether they would use a Traditional Pacific Healer if sick (willingness) and how often their child had seen a Traditional Pacific healer in the previous 12 months (use). These questions were asked at multiple measurement waves consisting of 6 week, 4 and 6 year for mothers, and 6 weeks, 1, 2, 4, and 6 year measurement waves for children. RESULTS: At 6 weeks 48% of mothers were willing to use TPH and this decreased to 36% at year 4 and 24% at year 6. Pacific born mothers, Samoan and Tongan mothers, and religious mothers were significantly more willing to use a TPH. Varied patterns of use were observed by children based on ethnicity and measurement wave. Like mothers--use by children declined as they aged. At 6 weeks 18% of children saw a TPH whilst 8% saw a TPH at age 6 years. Mothers amenable to using traditional healers are using them as supplemental to western medicine, rather than as a substitute. CONCLUSIONS: There is a steady reduction observed in mother's willingness and children's use of TPH in the PIFS over time. This raises the question of the whether provision of TPH is sustainable in NZ. There are significant differences in use of TPH by ethnicity. Further research that assesses reasons for visits, treatments provided, and costs may help explain the observed variations shown in this study. PMID- 22675807 TI - Impacts of inter- and intra- ethnic partnerships/relationships on traditional gift giving in a cohort of Pacific mothers. AB - Traditional gift-giving (TGG) is an important element of familial obligations among Pacific families. Migration from Pacific homelands to New Zealand and other countries has had an impact on participation in TGG., Many anecdotal accounts have suggested that TGG diminishes when Pacific persons marry outside their ethnic groups. While TGG is an indicator of social cohesion TGG can have direct influence on disposable income. The practice of TGG impacts on health as Income and social cohesion are key determinants of health. Thus TGG Health and social cohesion are closely interrelated and interdependent. The data for this paper is taken from a longitudinal cohort study of 1,398 Pacific children and their families in South Auckland, New Zealand. The study sought participants' responses to questions pertaining to the amounts gifted, the frequency of giving, recipients of the gifting and their reasons for participating and not participating in TGG. The assumption explored in this paper is that as Pacific peoples move outside their social sphere and become more acculturated with other ethnic groups, TGG was more likely to diminish rather than increase. This paper addresses the TGG participation rates among Pacific peoples in inter-ethnic relationships and intra-ethnic relationships. It argues that couples in an intra ethnic intimate relationship are more likely to participate in traditional gift giving than those who are in inter-ethnic intimate relationships. While this is true for most PI inter ethnic relationships the level of participation increases further with inter-ethnic intimate relationships among Tongans and Samoans who are also the largest participators of all ethnic groups in traditional gift giving. PMID- 22675809 TI - A comparison of parenting practices between Samoan parents living in New Zealand and Samoa. AB - This study compares the nurturing and disciplinary practices of Samoan parents living in New Zealand with those of Samoan parents living in Samoa. Mothers and fathers with two-year-old children resident in each country completed a modified version of the Parent Behavior Checklist Multivariable logistic regression revealed that fathers in NZ were less nurturing and more disciplinarian than fathers in Samoa and mothers in NZ. Older parents were less nurturing but used less harsh discipline than younger parents, more educated parents were more nurturing, and parents on lower incomes were harsher disciplinarians. PMID- 22675810 TI - Prevalence and concordance of smoking among mothers and fathers within the Pacific Islands Families Study. AB - Cigarette smoking continues to contribute to the adverse mortality and morbidity rates for Pacific people in New Zealand. Using a large cohort study of Pacific families, this paper investigates the prevalence of smoking amongst Pacific mothers and fathers over three time-points, up to six years after the arrival of their child, to determine the concordance of both partners' reports of that smoking. Moreover, the patterns of smoking between partners were investigated over the three major Pacific ethnicities that reside in New Zealand (Samoan, Tongan and Cook Island Maori). Maternal self-report prevalence of smoking estimates ranged from 29.8% (1-year) to 33.6% (6-years). Paternal self-reported prevalence of smoking estimates were higher, and ranged from 37.9% (2-years) to 45.2% (6-years). The prevalence estimates for smoking in both mothers and fathers over all three measurement waves were higher than the 26.9% reported for Pacific people in the 2006/07 New Zealand Health Survey. No significant change in fathers' smoking prevalence over time was observed (p = 0.37); however a significant increase in mothers' smoking prevalence over time was noted (p = 0.002). Significantly, for about 25% of Pacific children both their parents were current smokers. Reducing infant exposure to tobacco smoke, by encouraging parents to quit smoking or banning smoking in the home and local environment (such as vehicles), is likely to bring about improved health outcomes for many Pacific children. Findings suggest that the interaction between parents should be considered rather than focusing on mothers' or fathers' smoking behaviour in isolation. PMID- 22675811 TI - Experience of physical abuse in childhood and perpetration of physical punishment and violence in adulthood amongst fathers: findings from the Pacific Islands Families Study. AB - BACKGROUND: Family violence is a serious and increasingly significant public health issue, both in New Zealand and internationally. While Pacific families in New Zealand experience disproportionately higher rates of violence compared to their Palagi counterparts, little epidemiological information exists about the effect of childhood abuse on Pacific fathers and whether it increases their proclivity on perpetrating violence. AIMS: To determine the prevalence of physical discipline administered to young Pacific children by their fathers and physical intimate partner violence (IPV) perpetrated against their partners; and to relate this to fathers' recalled levels of paternal and maternal childhood physical abuse. METHODS: A cohort of Pacific infants born during 2000 in Auckland, New Zealand, was followed. At 6-weeks and 2-years postpartum, home interviews conducted for mothers and experience of IPV within the last 12 months was measured using the Conflict Tactics Scale. At 1-year and 2-years postpartum, home interviews conducted for fathers and acts of physical discipline were elicited. At the 1-year phase, childhood history of physical abuse was also elicited using the Exposure to Abusive and Supportive Environments Parenting Inventory. Crude and adjusted generalised estimating equation models were employed for statistical analyses. RESULTS: The sample included 786 partnered fathers who were living with their child at the 1-year measurement wave and 579 fathers at the 2-years measurement wave. Smacking children was common (25.0% at 1 year, 81.7% at 2-years) and hitting children with an object was not infrequent (1.4% at 1-year, 14.2% at 2-years). Physical IPV perpetrated by the father ranged from 23.1% to 27.5% while severe IPV was reported by 10.1% to 14.3% of partners. Fathers subjected to higher levels of paternal physical abuse in childhood were significantly more likely to physically discipline their child with smacking than those with lower levels of paternal physical abuse, after adjusting for confounding factors; as were fathers subjected to higher levels of maternal physical abuse. While not statistically significant, fathers subjected to higher levels of paternal or maternal physical abuse in childhood had estimated odds ratios greater than unity for all other physical violence measures captured compared to fathers with lower levels of paternal or maternal physical abuse. DISCUSSION: Violence perpetrated by fathers on children and their partners appears common for many Pacific families in New Zealand. These findings highlight the deleterious effect of paternal and maternal physical abuse in childhood on subsequent physical violence and IPV in adulthood. To break this intergenerational cycle of violence, culturally targeted and specific approaches are needed to negate this complex and damaging phenomena. PMID- 22675812 TI - Reliability and validity of maternal recall of injuries in Pacific children: findings from the Pacific Islands Families Study. AB - BACKGROUND: Childhood injury is one of the leading causes of morbidity and mortality worldwide. Many epidemiological studies use self-report injury data to understand the pattern of injury, and to identify risk factors and potential injury countermeasures, but the veracity of these data is not without question. AIMS: To investigate the reliability and validity of the use of maternal recall of childhood injuries in a birth cohort study of Pacific mothers residing in New Zealand. METHODS: As part of the Pacific Islands Families Study (PIFS), this study included 1,354 Pacific children born in Auckland in 2000 whose mothers completed a questionnaire at 6-weeks, 1-year, 2-years, 4-years, and 6-years postpartum. Maternal reports of child injuries and medical attendance events reported were matched to listings held within the National New Zealand Health Information Service's National Medical Discharge Summary (NMDS) database. RESULTS: Overall, 120 child injury events were listed in the NMDS database and 139 in the PIFS questionnaires. Kappa statistics demonstrated a modest level of agreement between the NMDS database listings and the mothers reporting of childhood injuries over the six years postpartum. However, McNemar's test of symmetry revealed no systemic under-reporting by the mothers, suggesting that the use of maternal proxy reporting of childhood injuries is a valid measure in this population. DISCUSSION: While maternal proxy reporting of Pacific childhood injuries was found to be a valid measure, some evidence of misinterpretation of questions was found; suggesting continued vigilance and development of maternal completed childhood injury questionnaires is warranted. PMID- 22675813 TI - An exploration of physical activity, nutrition, and body size in Pacific children. PMID- 22675814 TI - Ten years of research for the Pacific Islands Families Study: a comparative review of publications. AB - In 2000, the Pacific Islands Families Study (PIFS) initiated research into developmental pathways of health outcomes for Pacific children and families. Not only was the study premised on addressing the gap in longitudinal research of Pacific peoples, it also aimed to increase Pacific-researcher capacity. After ten years of operation, this paper reviews the journal publications and Pacific authorship from the PIFS. The PIFS team published 55 journal articles in 29 peer reviewed journals. Forty-four (80.0%) of these articles had a Pacific author, including seven (12.7%) where the first-author was Pacific. Most articles used cross-sectional data (n = 38, 69.1%) and a quarter used longitudinal data (n = 15, 27.3%). Eighteen (62.1%) of the 29 journals that PIFS articles were published in were registered on the Journal Citations Report database, with 2009 5-year journal impact factors ranging from 1.064 to 6.504. The PIFS achieved a similar number of publications compared with the Dunedin Multidisciplinary Health and Development Study (DMHDS, n = 48) and Christchurch Health and Development Study (CHDS, n = 67). Further analysis, showed that the PIFS (27.3%) had the lowest proportion of publications using longitudinal data compared to the DMHDS (n = 37.5%) and CHDS (65.7%). This review provides a stocktake of publications in the first decade of the PIFS and shows that although the development of Pacific researcher capacity has been promising, greater attention must be given to increasing first-authorship of academic writing and to utilising longitudinal data to better understand the origins of health status of Pacific peoples. PMID- 22675815 TI - The future of the Pacific Islands Families Study: a future with unlimited potential. PMID- 22675816 TI - Some reflections on the Pacific Islands Families Study. PMID- 22675817 TI - Tracking--the Pacific Islands Families Study. PMID- 22675818 TI - A few words on the Pacific Islands Families Study. PMID- 22675819 TI - Me & the Pacific Islands Families Study--where it is now! PMID- 22675820 TI - [Resistance and challenges encountered in clinical neurosciences]. PMID- 22675821 TI - [Resistance to treatment in movement disorders]. AB - Therapeutic strategies for essential tremor (ET) and Parkinson's disease (PD) can be divided into two successive steps, one based on oral medications and the other, more invasive, using pumps or functional neurosurgery. When ET becomes refractory to propranolol, primidone and other, second-choice compounds, deep brain stimulation of the VIM nucleus of the thalamus can be considered. When PD becomes resistant to dopamine replacement therapy using various combinations of dopaminergic agents, then three options can be discussed: first, a subcutaneous apomorphine mini-pump, second, a jejunal levodopa-delivery system by means of percutaneous gastrostomy, and third, bilateral deep brain stimulation of the subthalamic nucleus. The above interventions are successful in about 80% of cases. PMID- 22675823 TI - [Treatment of chronic pain: transcranial stimulation of the motor cortex?]. AB - Chronic pain refractory to medical therapy poses a therapeutic challenge. The repetitive Transcranial Magnetic Stimulation (rTMS) and transcranial Direct Current Stimulation (tDCS) modulate brain activity offering a new approach. Current evidence suggests a potential therapeutic efficacy of motor cortex stimulation for the treatment of pain, but does not (yet) support their recommendation for clinical practice. These methods allow to deepen our knowledge in the pathophysiology of chronic pain while providing new therapeutic approaches. PMID- 22675822 TI - [Treatment of pharmacoresistant epilepsy: stimulated refractoriness]. AB - Antiepileptic drugs allow controlling seizures in 70% of patients. For the others, a presurgical work-up should be undertaken, especially if a focal seizure origin is suspected; however, only a fraction of pharmacoresistant patients will be offered resective (curative) surgery. In the last 15 years, several palliative therapies using extra- or intracranial electrical stimulations have been developed. This article presents the vagal nerve stimulation, the deep brain stimulation (targeting the mesiotemporal region or the thalamus), and the cortical stimulation "on demand". All show an overall long-term responder rate between 30-50%, but less than 5% of patients becoming seizure free. It is to hope that a better understanding of epileptogenic mechanisms and of the implicated neuronal networks will lead to an improvement of these proportions. PMID- 22675824 TI - [Drug-resistant headache: is it the end?]. AB - Chronic primary headache often cause significant interference with function and quality of life despite acute and preventive medicines. New treatments are emerging for pharmacologically intractable cluster headache and migraine. Occipital nerve stimulation in chronic cluster headache and botulinum toxin in chronic migraine represent the most promising therapies. PMID- 22675825 TI - [Treatment resistant depression: therapy and novel neuromodulatory treatments]. AB - Unipolar depression is among the leading cause of invalidity and disability adjusted life-years. Many depressed patients do not respond to several antidepressant treatments. Several treatments have been investigated in resistant depression using electrical or magnetic stimulation of the brain. In this field, electroconvulsivotherapy remains to date the only treatment validated for efficacy and security. Novel neuromodulatory treatments used in neurological conditions are currently under investigation. Vagus nerve stimulation and deep brain stimulation may offer long-term efficacy and therefore justify expensive and highly specialized treatment programs. PMID- 22675826 TI - [Multiple sclerosis: beyong first line therapies]. AB - We are currently experiencing a key period in the management of patients with relapsing remitting multiple sclerosis. The application of new criteria allows early diagnosis, thus at a stage when the available immune treatments are the most likely to show a good efficacy. The therapeutic offer is expanding but its complexity too. It is thus important, for a given patient, to assess as precisely as possible the degree of severity of his/her disease, in order to give the drug with the optimal risk/benefit ratio. PMID- 22675827 TI - [Hoarding disorder, symptom or separate disorder? Case report]. AB - Hoarding or compulsive hoarding, a severe form of collectionism, is currently described in various psychiatric disorders, including the famous Diogenes syndrome. The lack of remission despite a correct treatment in a patient that we have followed in the brief therapy center in Geneva, has led us to carry out an extensive Medline review, which revealed several interesting points. It seems that excessive hoarding, with a prevalence of 2,3 to 4,6%, has received increasing interest and there is an actual debate of distinguishing hoarding from other disorders. Thus, this field requires further attention to better understand its phenomenology. This case report describes an excessive hoarding disorder confirming the complexity of this trouble and the possibility to consider it as an independent diagnosis. PMID- 22675828 TI - [Whistle blowing in health care sector: finding balance between divergent interests]. PMID- 22675830 TI - [The face, weapon against regression]. PMID- 22675829 TI - [ The Europe of "Longevity without disabilities" ]. PMID- 22675831 TI - [AIDS: preventive self-care before infection?]. PMID- 22675832 TI - [Alcohol does not rock anymore?]. PMID- 22675833 TI - [Intestinal microbiome and blurred identity]. PMID- 22675834 TI - The fate of the Warsaw Ghetto Medical Faculty. AB - The Warsaw Ghetto, in existence from 1940 to 1943, was the largest ghetto in Nazi occupied Europe. The 400,000-500,000 Jews incarcerated within its walls were deprived not only of food and medicine but also of education. Nonetheless, Jewish physicians served the community as befits their profession, and against all odds obtained permission to conduct a course on sanitary measures to combat epidemics, which they transformed into a veritable, clandestine medical school. This review follows the fate of the school faculty, with an emphasis on the achievements of the survivors. PMID- 22675835 TI - Medicine and thought-styles: on the 50th anniversary of the death of Ludwik Fleck (1896-1961). PMID- 22675836 TI - The Israeli Annual FMF, Amyloidosis and Other Autoinflammatory Diseases Meeting (July 2011): a bridge spanning these entities. PMID- 22675838 TI - QT variability in amyloidosis of familial Mediterranean fever. AB - BACKGROUND: The association between familial Mediterranean fever (FMF) and increased risk for ventricular arrhythmias is controversial, and data on this subject are meager. OBJECTIVES: To evaluate QT variability index (QTVI) and other repolarization markers associated with arrhythmogenity in patients with amyloidosis of FMF. METHODS: The study group comprised 12 FMF patients with amyloidosis, and 14 age and gender-matched healthy subjects served as the control group. QT measurements were conducted according to accepted procedure, using computerized software for recording and analysis. RESULTS: No differences were found in clinical and demographic parameters in the study and control groups, except for hypertension which was more common in the FMF amyloidosis group. QTc and power spectral analysis of QT variability parameters were similar in both groups. Nevertheless, QTVI values in FMF amyloidosis patients were significantly higher than in healthy individuals (-1.02 +/- 0.38, vs. -1.36 +/- 0.32 respectively, P = 0.02). CONCLUSIONS: Compared with healthy controls, amyloidosis of FMF is associated with increased QTVI. It remains unknown whether this finding is solely amyloidosis related and whether it has any prognostic significance. PMID- 22675837 TI - Risk factors for amyloidosis and impact of kidney transplantation on the course of familial Mediterranean fever. AB - BACKGROUND: Amyloidosis of familial Mediterranean fever (FMF) may lead to end stage renal failure, culminating in kidney transplantation in some patients. OBJECTIVES: To assess demographic, clinical and genetic risk factors for the development of FMF amyloidosis in a subset of kidney-transplanted patients and to evaluate the impact of transplantation on the FMF course. METHODS: Demographic, clinical and genetic data were abstracted from the files, interviews and examinations of 16 kidney-transplanted FMF amyloidosis patients and compared with the data of 18 FMF patients without amyloidosis. RESULTS: Age at disease onset and clinical severity of the FMF amyloidosis patients prior to transplantation were similar to FMF patients without amyloidosis. Compliance with colchicine treatment, however, was much lower (50% vs. 98%). Posttransplantation, FMF amyloidosis patients experienced fewer of the typical serosal attacks than did their counterparts (mean 2214 days since last attack vs. 143 days). Patients with FMF amyloidosis carried only M694V mutations in the FMF gene, while FMF without amyloidosis featured other mutations as well. CONCLUSIONS: Compliance with treatment and genetic makeup but not severity of FMF constitutes major risk factors for the development of amyloidosis in FMF. Transplantation seems to prevent FMF attacks. The protective role of immunosuppressive therapy cannot be excluded. PMID- 22675839 TI - "Trap" the diagnosis: a man with recurrent episodes of febrile peritonitis, not just familial Mediterranean fever. AB - Monogenic periodic fever syndromes are characterized by recurrent episodes of fever, accompanied by localized inflammatory manifestations. Among them, familial Mediterranean fever (FMF) is the most studied and is by far the most prevalent periodic fever syndrome in Israel. We present a diagnostic workup of a patient suffering from a periodic fever syndrome, initially thought to be FMF and characterized by attacks of fever, severe abdominal pain, a migratory erythematous rash and conjunctivitis. The development of periorbital edema presenting as diplopia led to consideration of tumor necrosis factor receptor-1 associated periodic syndrome (TRAPS). Genetic tests confirmed the diagnosis. This case should alert us that even in Israel, a patient with periodic fever not fully consistent with the typical features of FMF, should be evaluated for other periodic fever syndromes. PMID- 22675840 TI - Familial Mediterranean fever, an amyloid thyroid goiter and an enlarged parathyroid gland. PMID- 22675841 TI - Multiple sclerosis in Israeli children: incidence, an clinical, cerebrospinal fluid and magnetic resonance imaging findings. AB - BACKGROUND: Multiple sclerosis (MS) occurs in young adults and infrequently appears in childhood. OBJECTIVES: To determine the incidence of MS and describe the clinical, cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) findings at onset of MS in children in Israel. METHODS: Incidence and case specific data were obtained through the MS Center Database and Israeli Health Statistics Census Data over 15 years, from 1995 to 2009, and compared between patients with childhood (< 12 years), juvenile (> or = 12 years, < or = 18 years) and adult (> 18 years) MS onset. RESULTS: Of 1129 eligible MS patients, we identified 10 (0.89%) with childhood-onset MS, 74 (6.55%) with juvenile-onset MS, and 1045 (92.56%) with adult-onset MS. There were 0 to 3 incident childhood cases/year, leading to an annual incidence of 0.1/100,000 among Israeli children; the incidence of juvenile and adult MS was 2.6 and 5.4/100,000, respectively. Neurological presentation among children with MS was optic neuritis, motor weakness or brainstem involvement. CSF oligoclonal immunoglobulin (IgG) were positive in 62.5%. The most frequent MRI finding was the occurrence of > or = 3 periventricular white matter lesions followed by corpus callosum lesions, with 71% co-occurrence. Cervical and thoracic lesions occurred in 33% and 43%, respectively. Time to second neurological event ranged from 0.3 to 4.2 years and none of the patients with childhood MS reached EDSS = 6.0 within a mean follow-up period of 8.4 years. CONCLUSIONS: Childhood-onset MS is rare, with an incidence of 0.1/100,000 Israeli children. Childhood MS does not differ significantly from juvenile and adult-onset MS in terms of clinical, laboratory and imaging findings. PMID- 22675842 TI - Diastolic double-product: a new entity to consider in normal-tension glaucoma patients. AB - BACKGROUND: Vascular insufficiency is considered to play an important role in the pathogenesis of normal-tension glaucoma (NTG). Autoregulation of blood flow in the eye has been shown to be impaired in NTG, resulting in the inability to compensate for changes in intraocular pressure or blood pressure in order to maintain adequate perfusion. OBJECTIVES: To evaluate the occurrence of combined bradycardia-hypotension during 24 hour monitoring of blood pressure and heart rate in patients with NTG. METHODS: Eleven NTG patients participated in the study. All had episodic symptoms of dizziness or lightheadedness, but were confirmed as not having a diagnosis of orthostatic hypotension. Twenty-four hour monitoring was performed with systemic blood pressure and heart rate automatically measured every 20 minutes during daytime and every hour during the night. The cardiac diastolic and systolic double products (dDP and sDP) at each reading were calculated by multiplying the heart rate by the respective blood pressure. dDP < 3600 and sDP < 5400 (corresponding to a heart rate of 60 beats/min and a blood pressure of 60 and 90 mmHg, respectively) were considered abnormally low, and dDP < 2500 and sDP < 4000 (corresponding to a heart rate 50 beats/min and a blood pressure of 50 and 80 mmHg, respectively) were considered severely abnormal. RESULTS: dDP was abnormally low in all 11 NTG patients on at least one occasion, the majority occurring during the nighttime hours, while abnormally low sDP was present in 8 of the 11 patients. The mean cumulative duration of low dDP readings was 4.2 +/- 3.2 hours. Severely low dDP readings were observed in six patients. CONCLUSIONS: Abnormally low dDP was recorded in all NTG patients, lasting more than an hour in the majority of cases. Abnormally decreased dDP may represent a state of cardiovascular autonomic dysregulation, resulting in low ocular perfusion in certain NTG patients. PMID- 22675843 TI - QT interval disturbances in elderly residents of long-term care facilities. AB - BACKGROUND: The QT interval reflects the total duration of ventricular myocardial repolarization. Disturbed QT--either prolonged or shortened--is associated with arrhythmia and is life-threatening. OBJECTIVES: To investigate an elderly population for disturbed QT interval. METHODS: We conducted a cross-sectional study on residents of long-term care wards in a geriatric hospital. Excluded were those with pacemaker, atrial fibrillation or bundle branch block. The standard 12 lead and lead 2 electrocardiograms in the patients' files were used for the evaluation of QT interval. RESULTS: We screened the ECGs of 178 residents. QTc prolongation based on the mean 12 ECG leads was detected in 48 (28%), while 45 (25%) had prolonged QTc based on lead L2. Factors associated with QT prolongation were male gender, chronic renal failure and diabetes mellitus. Short QT was found in 7 residents (4%) and was not related to any parameter. CONCLUSIONS: About one third of the elderly long-term care residents in our study had QT disturbances. Such a considerable number warrants close QT interval follow-up in predisposed patients. PMID- 22675844 TI - Does low molecular weight heparin influence the triple test result in pregnant women with thrombophilia? AB - BACKGROUND: The triple test serum markers for Down's syndrome screening may be altered because of various conditions other than chromosomal trisomies. OBJECTIVES: To assess the profile of mid-trimester triple test serum markers in a cohort of women treated with low molecular weight heparin (LMWH) for thrombophilia since the first trimester. METHODS: Women with inherited or acquired thrombophilia treated with LMWH prior to 12 weeks gestation were followed between October 2006 and September 2009 at our obstetric outpatient clinic. The second-trimester screening test for Down syndrome was calculated from the combination of triple serum markers and maternal age, and expressed as a multiple of the gestation-specific normal median (MoM). Reference MoM values were calculated from the local population. Data on pregnancy outcome were obtained from patient records. RESULTS: The median human chorionic gonadotropin (hCG) level of women with inherited thrombophilia was 0.87 MoM, compared to 0.99 MoM in controls (P = 0.038) and compared to 1.355 MoM in women with acquired thrombophilia (P = 0.034). In contrast, alpha-fetoprotein MoMs did not differ significantly between women with inherited and women with acquired thrombophilia (0.88 vs. 0.99 MoM, P = 0.403). CONCLUSIONS: The triple test serum markers may be altered in thrombophilia patients treated with LMWH. Clinicians should consider offering these patients the first-trimester nuchal translucency test and other sonographic markers that are probably unaffected by the underlying maternal disease and/or treatment modality. PMID- 22675845 TI - Pediatric demyelinating diseases: multiple sclerosis or not? PMID- 22675846 TI - Partial-breast irradiation: is it the time for prime time? PMID- 22675847 TI - Intraoperative radiotherapy for breast cancer. PMID- 22675848 TI - Glycemic control in the intensive care unit: between safety and benefit. PMID- 22675849 TI - Pancreatitis due to hypercalcemia in a young adult. PMID- 22675850 TI - Glycogenic hepatopathy: a rare disease that can appear and resolve rapidly in parallel with glycemic control. PMID- 22675851 TI - The physician and the media: flippant professionalism? PMID- 22675852 TI - Risk behaviors and sexually transmitted diseases in gay and heterosexual men attending an STD clinic in Tel Aviv, Israel: a cross-sectional study. AB - BACKGROUND: The increase in human immunodeficiency virus (HIV) among men who have sex with men (MSM) in Israel during the last decade raises concerns regarding other sexuallytransmitted diseases (STD) in MSM, which are yet undetermined. OBJECTIVES: To evaluate the STD burden among MSM and heterosexuals visiting the Tel Aviv walk-in STD clinic. METHODS: Records of all male patients who attended the clinic once were reviewed to identify demographic characteristics, behavioral attributes, and test results. RESULTS: Between 2002 and 2008, 1064 MSM (22%) and 3755 heterosexuals (78%) visited the clinic once. Positivity rates in MSM for HIV, urethral Neisseria gonorrhoea and infectious syphilis were higher than in heterosexuals (2.5%, 2.5%. 0.7% vs. 0.6%, 1.3%, 0.3%, respectively), while urethral Chlamydia trachomatis was higher in heterosexuals than in MSM (2.7% and 1.4%, respectively). MSM tested in our clinic were younger than heterosexuals (P<0.001), more commonly circumcised (P=0.03) and Israeli-born (P<0.001), used substances during sex (P=0.04), and had prior STD (P<0.001), a greater number of sexual partners (P<0.001), and earlier sexual debut (P=0.02). The final multivariate results for MSM to be diagnosed with HIV/STD were greater number of sexual contacts, previous diagnosis with STD, and infrequent use of condom during anal intercourse. CONCLUSIONS: MSM visiting the Levinsky Clinic had higher rates of HIV/STD than heterosexual males, which correlated with their higher-risk behaviors. The unique characteristics of MSM found in our study, such as sex work, substance use, previous diagnosis of STD, multiple partners and inconsistent use of condom during anal sex should be addressed with innovative interventions to prevent STD/HIV in the gay community in Israel. PMID- 22675854 TI - Streptokinase fibrinolysis protocol: the advantages of a non-operative treatment for stage II pediatric empyema patients. AB - BACKGROUND: Pediatric empyema necessitates prompt resolution and early hospital discharge with minimal morbidity. However, the most effective treatment approach is not yet established. OBJECTIVES: To assess the efficacy of an intrapleural streptokinase washing protocol as a non-operative treatment for stage II pediatric empyema as compared to operative decortications, by the number of pediatric intensive care unit (PICU) admissions, length of PICU stay, and hospitalization duration. METHODS: We retrospectively evaluated 75 consecutive pediatric empyema cases for the period January 2006 to December 2009. Since July 2007 we have used repeated streptokinase-based pleural washing for stage II patients whose condition did not improve with chest drainage RESULTS: Before July 2007, 17 of 23 stage II empyema patients underwent decortication, compared to only 1 of 21 after July 2007. Non-operated children were admitted to the PICU less frequently than those who were operated (83% vs. 31%, p = 0.0006) and spent less time in the PICU (2.56 +/- 1.92 vs. 1.04 +/- 1.9 days, P= 0.0148); there was no significant statistical difference in overall hospitalization (13.33 +/- 3.69 vs.11.70 +/- 5.74 days, P= 0.301). CONCLUSIONS: Using intrapleural streptokinase washing as a non-operative treatment for stage II pediatric empyema yielded comparable success rates to the operative approach, with less morbidity. PMID- 22675853 TI - Syphilis outbreak among men who have sex with men, Tel Aviv, Israel, 2008-2009. AB - BACKGROUND: Outbreaks of syphilis have been described among men who have sex with men (MSM) in many western urban communities in the last few years. OBJECTIVES: To describe the first reported outbreak of syphilis among MSM in Israel within a decade of a constant increase in human immunodeficiency virus (HIV) prevalence. METHODS: All patients diagnosed with syphilis were contacted and asked about their sexual behavior, substance use and previous infections. All were tested for HIV and a phylogenetic analysis was performed. RESULTS: A total of 23 (59%) of all 39 male patients diagnosed with primary or secondary syphilis between August 2008 and August 2009 were interviewed. All were MSM and performed anal intercourse, while 13 (55%) reported unprotected anal intercourse. Most participants (21, 91%) practiced unprotected oral intercourse. Nine participants (39%) reported unprotected oral intercourse while using condoms during anal intercourse. Ten participants (43%) reported sexual contacts while traveling abroad in the previous few months. Most participants (96%) were co-infected with HIV, and 15 (68%) were already aware of their HIV infection. Fifteen (66%) reported the use of recreational drugs, alcohol, or both before or during sex. No common source or core transmitters were identified. CONCLUSIONS: This syphilis outbreak included MSM who were co-infected with HIV and were characterized by risky sexual behavior including multiple partners, unprotected anal intercourse and substance use. Future targeted interventions should focus on HIV-infected MSM for secondary prevention. PMID- 22675855 TI - Characterization of movement disorders in patients with familial Creutzfeldt Jakob disease carrying the E200K mutation. AB - BACKGROUND: While myoclonus and ataxia are considered common in patients with familial Creutzfeld-Jakob disease (fCJD), other movement disorders are less prevalent. OBJECTIVES: To systemically evaluate the frequency of extrapyramidal signs and movement disorders in patients with fCJD. METHODS: A detailed neurological examination, with special emphasis on movement disorders and extrapyramidal signs, was conducted in 43 consecutive symptomatic CJD patients (26 males and 17 females; mean age 58.7 +/- 8.9 yrs, range 43-77 years) carrying the E200K mutation in the PRNPgene. RESULTS: Limb or gait ataxia was noted in 38 patients (88%) (37 patients, 86%, had ataxia at presentation). Myoclonus was evident in 25/43 patients (58%) (21 patients, 49%, at presentation). In 95% of the patients (41/43) (37/43, 86% at presentation) at least one extrapyramidal sign throughout the disease course was noted, the most prevalent being rigidity (28/43, 65% of the patients; and 22/43, 51% at presentation), followed by the glabellar sign (24/43, 56% of the patients; and 22/43, 51% at presentation), bradykinesia (19/43, 44%; and 15/43, 35% at presentation), dystonia (15/43, 35%; 12/43, 28% at presentation) and tremor (13/43, 30%; 12/43, 28% at presentation). CONCLUSIONS: In this unique population of fCJD patients, myoclonus was less prevalent than previously reported while other extrapyramidal signs were common and occurred at a relatively early stage of the disease. The high prevalence of movement disorders can be added to other phenomena characteristic of this familial disorder among Libyan lews. Whether this is attributable to the E200K mutation itself or to some other mechanism has still to be elucidated. PMID- 22675856 TI - The resurgence, in Israel, of human immunodeficiency virus and syphilis among men having sex with men. PMID- 22675857 TI - Is streptokinase fibrinolysis the best treatment for empyema in pediatric patients? And must we tap every cirrhotic patient with bilateral pleural effusion? PMID- 22675858 TI - Hip arthroscopy: an emerging technique and indications. AB - Hip arthroscopy is one of the most rapidly evolving arthroscopy techniques. It combines the benefits of a minimally invasive procedure and a short rehabilitation period. Improved instrumentation and technical skills have advanced our ability to accurately diagnose and treat various conditions. The role of this procedure continues to evolve with new indications that might change the outcome of degenerative joint disease of the hip joint. Hip arthroscopy is indicated for both traumatic and atraumatic intra and extra-articular conditions. Femoroacetabular impingement (FAI) is increasingly recognized as a disorder that can lead to progressive articular chondral and labral injury. A variety of arthroscopic techniques allows the treatment of labral and acetabular rim pathology as well as peripheral compartment femoral head-neck abnormalities. It is now recognized that labral tears that were traditionally treated with simple debridement are often associated with underlying FAI. Hip arthroscopy is also being used for surgery to the structures surrounding the hip as snapping hip syndromes, greater trochanteric pain syndrome, and arthroscopic repair of abductor tendon tears. Better understanding of the arthroscopic anatomy, improved operative techniques, lowered complication rate and objective outcome measuring tools will further define the optimal role of hip arthroscopy and improve its outcome. PMID- 22675859 TI - An approach to the continuous dopaminergic stimulation in Parkinson's disease. AB - Dopaminergic neurons in the basal ganglia normally fire in a continuous manner, maintaining the striatal dopamine concentration at a relatively constant level. In Parkinson's disease, dopaminergic treatment produces a discontinuous stimulation, inducing an intermittent pulsatile activation of the striatal receptors. It is likely that the oscillations in the dopamine level in the striatum contribute to the development of motor complications. Treatment with long-acting dopaminergic agents, or providing a more continuous dopaminergic effect in the striatum, has been associated with fewer clinical motor complications. This review describes the state-of-the-art approach to achieve the desired continuous dopaminergic stimulation, providing patients with the best clinical effect and probably minimal motor complications. PMID- 22675860 TI - Regulatory T cells in allergic asthma. AB - Defective immunological suppression can be a cause of the inflammation that leads to an allergic condition such as asthma. Suppressor regulatory T cells (Tregs) are essential for inducing and maintaining immunological tolerance to foreign and self-antigens, including allergens. Tregs are apparently altered in number and function in allergic asthmatic patients. Some treatments that ameliorate asthma symptoms lead to an increase in the number and functional impairment of Tregs, indicating that these cells play an important role in the anti-inflammatory effect of those medications. PMID- 22675861 TI - Beta blocker therapy, decompensated heart failure, and inotropic interactions: current perspectives. AB - Beta blockers are a fundamental treatment in chronic heart failure (HF), yet concern and disagreement regarding their role in the treatment of decompensated HF and during hospitalization are common in clinical practice. This review summarizes the literature on various aspects of beta blocker treatment during acute and chronic decompensated HF. In recent years evidence has accumulated concerning the efficacy and tolerability of beta blockers in decompensated HF. Clinical analyses show that withdrawal of chronic beta blockade should be avoided when possible during hospitalization and that beta blockertherapy be initiated as soon as hemodynamic stability and a euvolemic state are achieved. This strategy may increase adherence to beta blockers after discharge and lower rehospitalization and mortality rates. We also discuss the various positive inotrope regimens (phosphodiesterase inhibitors, levosimendan, dobutamine) and their interactions with beta blockers in decompensated HF. PMID- 22675862 TI - Spontaneous bacterial empyema caused by Streptococcus pneumoniae. PMID- 22675863 TI - Glomus tumor of the stomach. PMID- 22675864 TI - Drug-induced palate osteonecrosis following nasal surgery. PMID- 22675865 TI - Persistent carbapenem-resistant Klebsiella pneumoniae bacteremia in a patient with acute lymphoblastic leukemia. PMID- 22675866 TI - Arachnoid granulation masquerading as lateral sinus vein thrombosis. PMID- 22675867 TI - Angiofibroma of the nasal vestibule in a 56 year old woman. PMID- 22675868 TI - Skin rash, dyspnea, weight loss and leg edema in a 59 year old woman with amyloidosis. PMID- 22675870 TI - The so-called vulnerable child. PMID- 22675869 TI - Advantage of inappropriate imaging? PMID- 22675871 TI - A disappointing prescribing journey. PMID- 22675872 TI - Competence audit a 'nightmare'. PMID- 22675873 TI - Linking early healthy attachment with long-term mental health. PMID- 22675874 TI - All children must be protected. PMID- 22675875 TI - Learning the art and science of nursing children. PMID- 22675876 TI - Caring for medically fragile children. PMID- 22675877 TI - Supporting children to be 'boss of their bowels'. PMID- 22675878 TI - Breastfeeding and drugs. PMID- 22675879 TI - Primary health care--a highly contested arena. PMID- 22675880 TI - Closing the gap--it's everyone's responsibility. PMID- 22675881 TI - Advancing NZNO's professional agenda. PMID- 22675882 TI - Bringing health care to displaced people in Burma. PMID- 22675883 TI - Supporting breastfeeding. PMID- 22675884 TI - Workload management concerns emergency department nurses. PMID- 22675885 TI - Delivering neurosurgical nursing care to children. PMID- 22675886 TI - All 'dental' life is there. PMID- 22675887 TI - Should deciduous teeth be restored? Reflections of a cariologist. AB - Whether deciduous teeth should be restored has caused controversy for at least 150 years and the argument rages on. Dental caries is a controllable process. The role of operative dentistry and restorations, as far as caries control is concerned, is to make cavitated, uncleansible lesions accessible to plaque control. However, deciduous teeth are exfoliated and perhaps non-operative treatments (plaque control, fluoride, diet) are all that are required to take cavitated teeth pain-free to exfoliation. Are such techniques child-friendly, obviating the need for anaesthesia or the use of handpieces? Alternatively, are they wanton neglect? This paper is written by a cariologist who never treated children, to present alternative managements and rehearse these arguments from a cariological perspective. CLINICAL RELEVANCE: This paper might serve as a discussion document for a group of dentists deciding practice policy with regard to the management of caries in deciduous teeth. PMID- 22675888 TI - Aphasia--the hidden disability. AB - Aphasia is an acquired language disorder due to brain damage and which may include difficulty in producing or comprehending spoken or written language. Stroke is the commonest cause and each year 50,000 new patients develop aphasia. People with aphasia differ in their speech output and in their fluency. Some people communicate reasonably well, while others have very limited powers of expression. This review will describe the neurology of speech and aphasia, and will focus on the role of the speech and language therapist in dealing with people with aphasia. CLINICAL RELEVANCE: Dentists and their staff should be aware that after a stroke some people are unable to talk or have limited powers of expression. Comprehension might be impaired and people with aphasia may be unable to grasp some common language, such as appointment letters and patient information. PMID- 22675889 TI - Contemporary denture base resins: Part 2. AB - Provision of partial and complete dentures constructed from resin is commonplace and a satisfactory outcome requires the consideration of the properties of the resin, the oral tissues and prosthodontic principles. This second of a two-part series examines the advantages and disadvantages of flexible nylon denture base resins, which have found popularity for the provision of partial dentures. Adverse effects of denture base resins are examined and the benefits and shortcomings of softliners are explored. Chairside adjustment and polishing, and denture hygiene are also discussed. CLINICAL RELEVANCE: Knowledge of contemporary denture base resin systems will help to achieve optimal outcomes in removable prosthodontics. PMID- 22675890 TI - Ionizing radiation regulations and the dental practitioner: 1. The nature of ionizing radiation and its use in dentistry. AB - Legislation governing the use of ionizing radiation in the workplace and in medical treatment first became law in 1985 and 1988, being superseded by the Ionizing Radiations Regulations 1999 (IRR99) and the Ionizing Radiation (Medical Exposure) Regulations 2000, (IR(ME)R 2000), respectively. This legislation ensures a safe environment in which to work and receive treatment and requires that those involved in the radiographic process must be appropriately trained for the type of radiographic practice they perform. A list of the topics required is detailed in Schedule 2 of IR(ME)R 2000 and is paraphrased in Table 1, with the extent and amount of knowledge required depending on the type of radiographic practice undertaken. CLINICAL RELEVANCE: Virtually all dental practitioners undertake radiography as part of their clinical practice. Legislation requires that users of radiation, including dentists and members of the dental team, understand the basic principles of radiation physics, hazards and protection, and are able to undertake dental radiography safely with the production of high quality, diagnostic images. PMID- 22675892 TI - Posterior composites: a practical guide revisited. AB - Direct placement resin composite is revolutionizing the restoration of posterior teeth. Compared to amalgam, its use not only improves aesthetics but, more importantly, promotes a minimally invasive approach to cavity preparation. Despite the benefits, the use of composite to restore load-bearing surfaces of molar and premolar teeth is not yet universally applied. This may be due to individual practitioner concerns over unpredictability, time and the fact that procedures remain technique sensitive for many, particularly with regard to moisture control, placement and control of polymerization shrinkage stress. New materials, techniques and equipment are available that may help to overcome many of these concerns. This paper describes how such techniques may be employed in the management of a carious lesion on the occlusal surface of an upper molar. CLINICAL RELEVANCE: Direct posterior composite is the treatment of choice for the conservative restoration of primary carious lesions. PMID- 22675891 TI - Sectional dentures revisited. AB - Sectional dentures are constructed in separate parts which join together intra orally to create a single prosthesis. They are used to exploit undercuts around teeth, hard and soft tissues which require more than one path of insertion, and are usually of split pin or locking bolts design. By using two case studies, we aim to illustrate the provision of sectional dentures and to which situations their uses are best suited. A 30-year-old male was referred to the Department of Prosthetics at the Birmingham Dental Hospital for a replacement upper partial cobalt chrome denture of a Kennedy Class IV bounded saddle. The patient had a history of failed upper cobalt chrome removable partial dentures owing to loss of retention and poor stability over the previous 12 months. A 40-year-old female patient was referred by her GDP for restoration of a bounded saddle in the lower right quadrant with a history of intolerance to previous dentures. These two cases demonstrate the successful use of sectional dentures in the aesthetic zone. Although more technically demanding, they lie well within the scope of general practice and offer patients alternative solutions from dental implants and bridgework. These cases highlight the importance of the use of alternative prosthetic techniques which can be simple and achievable for all practitioners. CLINICAL RELEVANCE: Sectional dentures are a treatment modality for the edentulous space where the presence of one or more undercuts prevents restoration by more conventional techniques. This paper highlights some of the situations in which sectional dentures can be employed and emphasizes their use in general practice. PMID- 22675894 TI - Comment: Me too 2. PMID- 22675893 TI - Subepithelial connective tissue graft used with platelet-rich plasma in treatment of gingival recession. AB - This paper describes the use of subepithelial connective tissue graft with platelet rich plasma in the treatment of gingival recession. There was complete root coverage in both the cases and the coverage is still maintained after 4 years. CLINICAL RELEVANCE: Subepithelial connective tissue grafting with platelet rich plasma may be an effective way to treat gingival recessions. Use of platelet rich plasma provides the clinician with an autologous source of growth factors to accelerate healing. PMID- 22675895 TI - Molar-incisor hypomineralization (MIH). PMID- 22675896 TI - Removable appliances. PMID- 22675897 TI - Working width--where to start and where to end? PMID- 22675898 TI - Oral cancer: comprehending the condition, causes, controversies, control and consequences. 15. Salivary and taste complications. PMID- 22675899 TI - Technique tips--modified transpalatal appliance: a simple non-invasive technique for maxillary molar intrusion. PMID- 22675900 TI - Medical conditions in dental practice. Case 93. Physical signs for the general dental practitioner. Osteogenesis imperfecta. PMID- 22675901 TI - The current range and diversity of research and theory in developmental psychology. PMID- 22675902 TI - Loneliness in childhood: toward the next generation of assessment and research. AB - Loneliness is a sad, even painful emotional experience that is thought to result from deficiencies in the quantity or quality of one's social relationships. Assessments of loneliness have evolved to typically include diverse item content that assesses the causes of loneliness as well as the emotional experience of loneliness itself. This embedding of hypothesized causes in the assessment of loneliness creates pervasive problems in drawing valid conclusions from empirical research on loneliness. In this chapter, we review major historical and contemporary perspectives on loneliness and then describe how widely used assessments have led to the development of a literature in which key questions about the causes of loneliness, the influence of gender on the experience of loneliness, and the developmental course of loneliness remain unanswered. We argue for the use of loneliness assessments that focus purely on the emotional experience of loneliness without including hypothesized causes. PMID- 22675903 TI - Cognitive and linguistic correlates of early exposure to more than one language. AB - This chapter reviews recent studies of cognitive and linguistic correlates of exposure to two languages in infancy and early childhood. Most of the studies reviewed directly compare monolingual children to those who are exposed to two languages. The cognitive correlates include enhanced executive functioning (especially inhibitory control), and Theory of Mind. The linguistic correlates include smaller vocabularies in each language, different word-learning strategies, slower lexical access, and enhanced pragmatic and metalinguistic skills. Issues in interpreting group differences, in particular, whether such differences should be interpreted as deficits, are discussed. PMID- 22675904 TI - The legacy of early interpersonal experience. AB - Despite decades of research on social development, the question of whether early interpersonal experiences play an important role in human development is just as controversial today as it was decades ago. In this chapter, we argue that there are at least three reasons why this debate has remained unsettled. First, outside of a few landmark longitudinal studies, relatively few investigations have prospectively charted the long-term correlates of experiences with primary caregivers in the first 3 years of life. Second, most analyses of datasets focused on the legacy of early experience have emphasized two-wave test-retest analyses. We contend that, to distinguish between enduring versus merely transient effects of early experience, it is instead necessary to study the pattern of associations that are observed across multiple assessment occasions. Third, despite decades of stinging critiques by behavior-genetic scholars, not enough attention has been paid in social developmental research to determining whether the robust correlations identified between parental behavior and child outcomes are genetically mediated. In this chapter, we discuss each of these issues, in turn, and review recent conceptual models and empirical data that help to address them. PMID- 22675906 TI - Social-emotional development through a behavior genetics lens: infancy through preschool. AB - The field of developmental behavior genetics has added significantly to the collective understanding of what factors influence human behavior and human development. Research in this area has helped to explain not only how genes and environment contribute to individual differences but also how the interplay between genes and environment influences behavior and human development. The current chapter provides a background of the theory and methodology behind behavior genetic research and the field of developmental behavior genetics. It also examines three specific developmental periods as they relate to behavior genetic research: infancy, toddlerhood, and early preschool. The behavior genetic literature is reviewed for key socioemotional developmental behaviors that fit under each of these time periods. Temperament, attachment, frustration, empathy, and aggression are behaviors that develop in early life that were examined here. Thus, the general purpose of this chapter is to provide an overview of how genes and environment, as well as the interplay between them, relate to early socioemotional behaviors. PMID- 22675905 TI - Some (but not much) progress toward understanding teenage childbearing: a review of research from the past decade. AB - In the decade and a half since Coley and Chase-Lansdale's (1998) review of teenage childbearing, there have been a number of studies investigating teenage childbearing from a developmental psychological perspective. Many of these studies have focused primarily on identifying individual, familial, and socioeconomic risk factors in childhood and adolescence that are highly correlated with teenage sexual behavior and teenage childbearing. We have an emerging understanding of teenage childbearing as the culmination of a complex cascade of experiences and decisions that overlap greatly with the risks for antisocial behavior. Much of this research, however, is limited by its reliance on correlational and cross-sectional research designs, which are not able to rigorously test causal inferences or to identify mechanisms associated with teenage childbearing. Innovative studies using large, nationally representative samples with quasi-experimental and longitudinal designs can expand on such descriptive studies. In particular, quasi-experimental studies can help answer questions about which risk factors are causally associated with teenage childbearing and suggest potential mechanisms that can explain how teenage childbearing is associated with poor outcomes. Future studies also will need to incorporate more precise measures of developmental processes and explore heterogeneity among adolescent mothers. Although advances have been made in the psychological study of teenage childbearing, more research is needed in order to answer important questions about which psychological processes are causally related to teenage childbearing and how teenage childbearing is associated with poor outcomes for young mothers and their offspring, PMID- 22675907 TI - The relation between space and math: developmental and educational implications. AB - There is a well-known relation between spatial ability and mathematics dating back to the work of early twentieth century factor analysts. This connection is a ripe opportunity for educators, who might use spatial training to improve math learning. However, a closer look at the literature reveals gaps that impede direct application. The primary problem is that although this relation is well established in older children and adults, its emergence in early development and subsequent developmental interactions are not well documented. Moreover, there is a need for more mechanistic explanations that might be leveraged to improve math education. In this chapter, we attempt to address these issues by reviewing the existing literature to identify instances where answers are available and others where further research is needed. PMID- 22675909 TI - Producing and understanding prosocial actions in early childhood. AB - Early prosocial development has become a topic of great interest in recent years as experimental studies have provided evidence that instances of prosocial action can already be found in the second year of life. In this contribution, we review the recent literature on young children's production of prosocial actions, in particular helping, sharing, and comforting, and their understanding of others' prosocial behavior. We summarize the novel insights gained by recent studies and point to directions for future studies. Overall, we suggest that while the field consists of considerable knowledge about the developmental timeline of prosocial behavior, more research is needed to examine and better understand underlying social-cognitive mechanisms. PMID- 22675908 TI - Testing models of children's self-regulation within educational contexts: implications for measurement. AB - Young children's self-regulation has increasingly been identified as an important predictor of their skills versus difficulties when navigating the social and academic worlds of early schooling. Recently, researchers have called for greater precision and more empirical rigor in defining what we mean when we measure, analyze, and interpret data on the role of children's self-regulatory skills for their early learning (Cole, Martin, & Dennis, 2004; Wiebe, Espy, & Charak, 2008). To address that call, this chapter summarizes our efforts to examine self regulation in the context of early education with a clear emphasis on the need to consider the comprehensiveness and precision of measurement of self-regulation in order to best understand its role in early learning. PMID- 22675911 TI - [It is only about sexuality]. PMID- 22675910 TI - Food and family: a socio-ecological perspective for child development. AB - Using an ecological framework (Bronfenbrenner, 1979), and the specific concepts outlined in the "Six-C's Model" of contributors to child overweight and obesity by Harrison et al. (2011), this chapter reviews recent evidence linking the dynamics of food consumption to socialization practices, child health, media influences, and contextual factors such as poverty and culture. We discuss the multiple influences of food in a child's life, focusing on each of the different levels of the Six-C's Model, highlighting the influences of parental feeding practices, family mealtimes, and television viewing on food consumption. We provide examples of childhood obesity and household food insecurity to illustrate how food and family connect across different ecologies to result in either poor or optimal outcomes for children under different levels of risk. We conclude with recommendations for research, practice, and policy surrounding children's food consumption. PMID- 22675912 TI - [A level playing field in the nursing home]. PMID- 22675913 TI - [Homes for the aged and nursing homes. Managing diversity - increasing quality]. PMID- 22675914 TI - ["Horizons" project. Recommendations for general practice]. PMID- 22675915 TI - [Nursing guided patient care pathways. Patient oriented care from admission to discharge]. PMID- 22675916 TI - [Psychosocial and nursing care in mastectomy. First the breast, then femininity is lost]. PMID- 22675917 TI - [Application in general practice. Guidelines for nursing]. PMID- 22675918 TI - [Center for Evidence Based Nursing. An (almost) eternal construction site]. PMID- 22675920 TI - [Shared nursing - medicine education. Interprofessional seedlings]. PMID- 22675919 TI - [Academy - general practice partnership. Short nursing care channel between science and general practice]. PMID- 22675921 TI - [Zuger faculty for health personnel education. Success in controlling salary discrimination]. PMID- 22675922 TI - [Needs based nursing care in gynecology. "My symptom diary"]. PMID- 22675923 TI - [Living together, a difficult task]. PMID- 22675924 TI - [What manner of health promotion in the years ahead? Improving life skills]. PMID- 22675925 TI - [Acute confusion in the elderly. Assessment and preventive measures]. PMID- 22675926 TI - [Open questions concerning the flat rate per case. Refer to the DRG!]. PMID- 22675928 TI - [People are not all alike, but are equally important.[]. PMID- 22675927 TI - [Loss of vital energy. Former wounds, scars of today]. PMID- 22675930 TI - [Significance expression and relationships with endothelin-1, matrix metalloproteinase-9 in the laryngeal carcinoma]. AB - OBJECTIVE: To evaluate the expression of endothelin-1(ET-1) and matrix metalloproteinase-9 (MMP-9) in laryngeal carcinoma and their correlations with clinical features. METHOD: The expression of ET-1 and MMP-9 was detected by immunohistochemical method in 58 specimens of laryngeal carcinoma, 28 specimens of polyps of vocal cord and 19 specimens of normal laryngeal tissues. RESULT: The expressions of ET-1, MMP-9 in laryngeal carcinoma were remarkably higher,compared to polyps of vocal cord and normal laryngeal tissues (P < 0.05). The expression of ET-1, MMP-9 was associated with clinical stage, T stage and lymph node metastasis. Expression levels of ET-land MMP-9 correlated significantly with each other (r(s) = 0.693, P < 0.05). CONCLUSION: The expression of ET-1 and MMP-9 may be the vital indexes in laryngeal carcinoma. PMID- 22675929 TI - [Selective neck dissection and the management of the hypopharyngeal cancer]. AB - OBJECTIVE: To determine the most appropriate form of selective neck dissection(SND) in the hypopharyngeal cancer with cervical lymph node metastasis. METHOD: We have retrospectively analyzed the distribution and prevalence of cervical metastasis in 26 patients with hypopharyngeal squamous cell carcinoma from January 1998 to December 2008. All the patients underwent SND as part of the primary treatment. There were 34 elective SNDs and 17 therapeutic SNDs from 11 node-negative hypopharyngeal cancers and others node-positive. RESULT: Occult metastasis was found in 6 patients (55%) with cervical metastasis confined to level II and III. Clinical node-positive necks were all pathologically identified with 6.7%, 66.7%, 86.7%, 46.7%, and 20.0% of the prevalence of metastasis to level I, II, III, IV and V respectively. The regional recurrences were found in 4 patients during the follow-up, which were all from cN+ patients. No patient experienced level I recurrence. CONCLUSION: The results of this study suggest that SND (I-III) may be feasible for the treatment of cN0 hypopharyngeal cancer, which needs a larger sample to verify. Meanwhile, from our data, it has a satisfactory result to perform SND (II-V) with adjuvant radiotherapy for the cN+ patients. PMID- 22675931 TI - [Causes of vocal cord dyscinesia and its original factors after endotracheal intubation]. AB - OBJECTIVE: To research the causes of postintubation vocal cord dyskinesia and its contributing factors. METHOD: The causes of vocal cord dyskinesia were confirmed by laryngoscope, three-dimensional spiral CT, stroboscope, and the analysis of therapy. The factors relevant to the causes of vocal cord dyskinesia were analysed based on the following elements: (1) the anatomic or pathological condition of patients or the technical skills of anesthetists. (2) emaciated or obese body and neck. (3) the age of patients. (4) the duration of endotracheal tube retention. (5) the types of operations. (6) anesthesia procedure. RESULT: Among 135 patients, 128 cases (94.81%) manifested arytenoid dislocation, 7 cases (5.19%) vocal cord paralysis. The study showed that the vocal cord dyskinesia associated with anatomic or pathological condition of patients and technical skills of anesthetists (with intubation difficulty) accounted for 76.30%. The patients with relative emaciated body or neck accounted for 90.62% in cases without intubation difficulty. Age had no significant analytical relationship with vocal cord dyskinesia. Prolonged intubation (endotracheal tube retention over 12 hours) was accounted for only 17.64%. The incidence of vocal cord dyskinesia was nearly 0.5% in patients underwent cardio-thoracic surgery, accounting for 59.26% of all the patients. CONCLUSION: There are two major causes of vocal cord dyskinesia: arytenoid dislocation and vocal cord paralysis, and the rate of vocal cord dyskinesia could be reduced by the improvement of technical skill of anesthetists and/or sufficient attention to the intubation condition of patients. PMID- 22675933 TI - [Primary evaluation of the simplified Chinese version of STOP-Bang scoring model in predicting obstructive sleep apnea hypopnea syndrome]. AB - OBJECTIVE: To evaluate the predictive significance of the simplified Chinese STOP Bang (S-B) scoring model in predicting obstructive sleep apnea hypopnea syndrome(OSAHS). METHOD: A total of 114 cases with suspected OSAHS were included in this study. S-B questionnaire was filled before polysomnography (PSG) monitoring. According to the PSG monitoring results the patients were divided into simple snoring, mild, moderate and severe OSAHS groups. The average S-B scores and the ratio of patients with S-B score > or = 3 were compared among the four groups respectively. The accuracy of S-B scoring model was analyzed and predictive significance was evaluated. RESULT: Eighty nine of 114 (78.1%) patients were classified as being at high risk of OSAHS by S-B scoring. The S-B scores showed an accrescent tendency as the severity of OSAHS increased. The scores in the four groups were 2.74 +/- 1.39, 3.25 +/- 1.16, 4.30 +/- 1.20, 4.79 +/- 1.41 respectively. Significant difference in S-B scores was found between severe OSAHS group and the other three groups respectively (P < 0.01), and also between moderate OSAHS group and mild OSAHS/simple snoring group (P < 0 01). The ratio of patients with high risk of OSAHS predicted by S-B scoring in OSAHS group (85.7%) was significantly higher than that in simple snoring group (47.8%) (P < 0.01). The sensitivities of S-B scoring model for AHI > or = 5 > or = > 15 and > or = 30 were 85.7%, 92 5% and 100%, respectively; the negative predictive values were 48.0% ,80.0% and 100%. The coincidence rate of S-B scoring model with golden standard to diagnose OSAHS was 78 9 . The area under the ROC curve at AHI cutoff of greater than or equal to 5 was 0 774. CONCLUSION: S-B scoring model can be used to evaluate patients with high risk of OSAHS. It is a concise and easy-to use tool to screen and predict moderate and severe OSAHS with relative high sensitivity and negative predictive value. PMID- 22675932 TI - [Expression and their significance of Jab1 p27kip1 in laryngeal squamous cell carcinoma and Hep-2 cells]. AB - OBJECTIVE: To discuss the expression and the significance of Jab1 p27kip1 in laryngeal squamous cell carcinoma and Hep-2 cells. METHOD: Immunohistochemical method was used to examine the expressions of Jab1 and p27kip1 proteins in 50 cases laryngeal squamous cell carcinomas and 10 cases normal laryngeal tissues adjacent to laryngeal squamous cell carcinoma. Hep-2 cells were transfected with synthetic Jab1 siRNA by Lipofectamine 2000. RT-PCR method was adopted to examine the mRNA expression of the Jab1 and p27kip1 gene in Hep-2 cells which was treated with Jab1 siRNA II. RESULT: Clearly brown staining restricted to nucleus was considered as positive expression of Jab1 and p27kip1 protein. The expression rate of Jab1 protein in laryngeal squamous cell carcinoma was significantly higher than that of normal laryngeal mucosa, and the expression rate of protein p27kip1 in laryngeal squamous cell carcinoma was significantly lower than that of normal laryngeal mucosa. There was a negative relationship between Jab1 and p27kip1 protein in laryngeal squamous cell carcinoma. The expression of Jab1 mRNA was suppressed markedly after transfected by Jab1 siRNA II. As the reaction time increased, the expression of Jab1 mRNA of Hep-2 cells decreased significantly, and the expression of p27kip1 mRNA remained unchanged. CONCLUSION: The expression rate of Jab1 protein in laryngeal squamous cell carcinoma is significantly higher than that of normal laryngeal mucosa. There is a negative relationship between Jab1 and p27kiPl protein in laryngeal squamous cell carcinoma. After transfected by Jab1 siRNA II in the Hep-2 cells, the expression of Jab1 mRNA is suppressed markedly. Jab1 siRNA would be a good methodology for the further study. PMID- 22675934 TI - [Correlation between allergic rhinitis and childhood obstructive sleep apnea hypopnea syndrome]. AB - OBJECTIVE: To investigate the correlation between allergic rhinitis and obstructive sleep apnea-hypopnea (OSAHS) syndrome in children. METHOD: (1) According to medical history, physical signs, skin-prick test, serum sIgE, endoscopic examination and polysomnography, the incidence of allergic rhinitis was confirmed in 574 cases of childhood obstructive sleeping apnea-hypopnea syndrome in our hospital between July in 2008 to June in 2010. (2) Effects of anti-allergic drugs were observed on 78 children with OSAHS and allergic rhinitis meanwhile. RESULT: (1) 258 cases of allergic rhinitis were confirmed in 574 cases of OSAHS, accounting for 44.9% of the OSAHS cases and 50.4% of all cases of allergic rhinitis during the same period. Most of them were perennial allergic rhinitis (223 cases, 86.4%), and 72.5% of them were aroused by fungal allergen. Compared with other allergen, statistically significant difference was found (P < 0.05). (2) After receiving anti-allergic drugs regularly for 3 weeks, 40 cases suffering from mild and moderate OSAHS and allergic rhinitis, 3 cases out of 38 cases suffering from serious OSAHS and allergic rhinitis showed satisfactory results, while other cases had little improvement. CONCLUSION: Allergic rhinitis is closely related to childhood OSAHS, and perennial allergic rhinitis dominates. The most common allergen is fungal allergen, the second is house and flour dust mites. So for patients of mild and moderate OSAHS with allergic rhinitis, regular anti-allergic drugs can lighten OSAHS effectively and may make patients avoid surgery. Severe OSAHS cases can receive surgical intervention if prior anti allergic therapy fails. Anti allergic therapy should be adopted routinely after tonsillectomy and adenoidectomy in case of hypopnea due to hypertrophy of inferior turbinate or tubal torus in allergic rhinitis. PMID- 22675935 TI - [Result of Z-palatoplasty for treating severe obstructive sleep apnea hypopnea syndrome]. AB - OBJECTIVE: To investigate the efficacy and related factors of Z-palatoplasty for treating severe obstructive sleep apnea hypopnea syndrome (OSAHS). METHOD: Thirty two severe OSAHS patients with Friedman II and III oropharyngeal airway had Z palatoplasty. Twenty-three patients with modified Mallampti Index (MMI) III-IV had coblation tongue channeling (CTC) simultaneously. The patients were followed up for one year post operatively. RESULT: After operation, the apnea and hypopnea index (AHI) decreased from (54.74 +/- 20.38)/h to (22.72 +/- 18.36)/h; the lowest artery oxygen saturation (LSaO2 ) increased from (0.74 +/- 0.08) to (0.85 +/- 0.14); the Epworth sleep scale (ESS) decreased from (12.24 +/- 5.78) to (5.35 +/- 3.62); the percentage of time with oxyhemoglobin saturation below 0.90 (CT90) decreased from (31.48 +/- 20.15) to (15.73 +/- 12.29). All of the differences were statistically significant (P < 0.01). According to related criterion of chinese journal of otorhinolaryngology head and neck surgery in 2009, accumulative excellence rate was 71.9% and accumulative valid rate 84.4%. Six patients had temporary velopharyngeal insufficiency and returned to normal after 3 months. CONCLUSION: Z-palatoplasty is an effective and safe surgical approach for OSAHS patients with Friedman II/III. PMID- 22675936 TI - [Expression of programmed cell death 4 and its correlation with proliferation and apoptosis in laryngeal squamous cell carcinoma]. AB - OBJECTIVE: To study the expression of PDCD4 and its relationship with cell proliferation and apoptosis in laryngeal squamous cell carcinomas and to evaluate its clinical significance. METHOD: The immunohistochemical staining method was applied to investigate the expression of PDCD4 and Ki-67 in 60 laryngeal squamous cell carcinomas tissues and 21 their surrounding laryngeal normal mucosa tissues. TUNEL method was applied to detect the apoptosis. The proliferation index (PI) and apoptosis index (AI) were defined. RESULT: The positive rate of PDCD4 protein was significantly lower in laryngeal squamous cell carcinomas than that in the laryngeal normal mucosa tissues (P < 0.01). The expression of PDCD4 had relation with the differentiation grading and lymph node metastasis (P < 0.05), but not related to tumor sites and TNM stage. The PI of laryngeal squamous cell carcinomas tissues was higher than that of the normal laryngeal mucosa tissues (P < 0.01). No relation was found among PI and tumor sites, differentiation grading and lymph node metastasis. PI had correlation with TNM stage (P < 0.05). The AI of the cancer was higher than that of normal laryngeal mucosa tissues (P < 0.01). There was no relationship between AI and tumor sites, TNM stage and lymph node metastasis. AI correlated with differentiation grading (P < 0.01). The PI in PDCD4 positive group was significantly lower than in PDCD4 negative group (P < 0.05). The AI in PDCD4 positive group was significantly higher than in PDCD4 negative group (P < 0.05). CONCLUSION: The expression of PDCD4 is low in laryngeal squamous cell carcinomas and it may play important roles in occurrence and development of laryngeal squamous cell carcinomas through the inducing apoptosis and inhibiting proliferation. PMID- 22675937 TI - [Expression of Th1/th2 transcription factors and cytokines in laryngeal squamous cell carcinoma and its clinical significance]. AB - OBJECTIVE: To study the differentiation of Th1/Th2 on the levels of transcription factors and cytokines production in patients with laryngeal squamous cell carcinoma in peripheral blood mononuclear cells (PBMC). In addition, the relation of p53 and T-bet, GATA3 expression was discussed for understanding the role of T bet and GATA3 in metastasis. METHOD: The gene expression of Th1/Th2 type transcription factors T-bet, GATA3 and cytokines IFN-gamma, IL-4 were determined by RT-PCR and realtime RT-PCR from 49 patients with laryngeal squamous cell carcinoma and 30 normal controls. The expression of p53 was analyzed by immunohistochemistry. RESULT: Predominant expression of Th2 type cytokines was detected in 49 laryngeal squamous cell carcinoma patients. The expression rates of T-bet, GATA3, IFN-gamma and IL-4 was 42.86% (21/49), 71.43% (35/49), 26.53% (13/49), 63.27% (33/49) respectively. The expression rates of T-bet and IFN-gamma in patients were lower than in control group (P < 0.05), but the results of GATA3 and IL-4 were opposite (P < 0.05). The similar results were obtained by realtime PCR. The expression of p53 in patients was accompanied with lower expression of T betmRNA and higher expression of GATA3mRNA. CONCLUSION: There is predominant expression of Th2 type transcription factors and cytokines in PBMC of laryngeal squamous cell carcinoma patients. T-bet and GATA3 can be used as reference indicators for the metastasis of laryngeal squamous cell carcinoma. PMID- 22675938 TI - [The expression and correlation of inducible nitric oxide synthase, Bax and Bcl-2 in nasal polyps]. AB - OBJECTIVE: To detect the expressions of inducible nitric oxide synthase (iNOS), apoptosis-related gene Bax, Bcl-2 in nasal polyps,and discuss the their relationship. METHOD: The apoptosis of 30 cases of nasal polyps was detected by TUNEL assay. The expressions of iNOS and Bax, Bcl-2 was detected by immunohistochemical SABC method. The expressions of iNOS and Bax, Bcl-2 was measured by western blot. RESULT: 1) The weakly positive stained apoptotic cells were detected at the surface epithelial cells and glandular epithelial cells of nasal polyps by TUNEL assay. 2) Immunohistochemical method revealed that positive stainings of iNOS, Bax, Bcl-2 located in the cytoplasm of epithelial cells, glandular epithelial cells, endothelial cells and infiltrating inflammatory cells in nasal polyps. The expression of Bax was weak, while the expressions of iNOS and Bcl-2 were strong. 3) iNOS, Bcl-2 and Bax was detected by western blot. The expressions of these proteins were significantly different (P<0.01). The expression of iNOS and Bcl-2 had a positive correlation (r=0.851, P<0.01), while the expression of iNOS and Bax had a negative correlation (r=-0.714, P<0.01). CONCLUSION: The pro-apoptotic and anti-apoptotic proteins are co-existed in the nasal polyps, iNOS may play an important role in the pathogens of nasal polyps through inhibition of apoptosis. PMID- 22675940 TI - [Clinical diagnosis and treatment of 65 cases of acute adenoiditis]. PMID- 22675939 TI - [Anti-tumor peptide of tumstatin in the treatment of the transplantable model of human laryngeal squamous carcinoma in nude mice]. AB - OBJECTIVE: To study the effect of anti-tumor peptide of tumstatin on tumor growth of human laryngeal squamous carcinoma in nude mice and the underlying mechanism. METHOD: Nude mice model bearing laryngocarcinoma were established by using human laryngeal squamous carcinoma cell line (Hep-II). The animals were given tumstatin or PBS for 10 consecutive days. The volumes of the subcutaneous tumor were observed. The microstructure in which the general 2-step immunohistochemical examination was adopted and ultra-micro-structural changes of carcinoma after administration of tumstatin were observed under light and electron microscopes for pathology examination. RESULT: The differences was statistically significant in the net mice weight, tumor weight, tumor volume and tumor weight/net mice weight between the treatment group and the control group (P<0.01). The restrained percentage of tumor was 51.58%. The necrosis and apoptosis of the tumor cells and the angiogenesis reduction were found under light and electron microscope in the treatment group. MVD of the treatment group was lower than that of the control group (P<0.01). CONCLUSION: Tumstatin can significantly restrain the development of laryngocarcinoma. PMID- 22675942 TI - [Cat scratch disease: a report of 21 cases with literature review]. PMID- 22675941 TI - [Diagnosis and therapy of dermatomyositis associated with nasopharyngeal carcinoma and literature review]. PMID- 22675943 TI - [Research progress of the objective voice assessment]. AB - The voice is a complex multidimensional phenomenon. It is a drive through the lung airflow to vibrate the vocal cords, and then be perceived by the listeners. A multidimensional set of minimal basic measurements suitable for the voice diseases are proposed by the Committee on Phoniatrics of the European Laryngological Society in 2000. It includes five different aspects: the subjective physician perception (grade, roughness, breathiness), and subjective rating by the patient, videostroboscopy (closure, regularity, mucosal wave and symmetry), acoustics analysis and aerodynamics measurements. The first three are the subjective assessment of voice, these are not to be discussed in tis article. Only objective assessments of the voice and the latest research progress are summarized below. PMID- 22675944 TI - Physicians should be more open-minded about performing in vitro fertilization embryo transfer in women with diminished oocyte reserve and consider the couple's wishes and desires. AB - PURPOSE: By presenting anecdotal cases of women who conceived with IVF-ET despite very poor odds, this editorial hopes to make some of the infertility specialists to be more optimistic about the prognosis for pregnancy in women with diminished oocyte reserve. METHODS: Description of case reports where despite poor odds the couples elected to still attempt IVF-ET which appeared to be needed for conception to be possible. RESULTS: Five cases are presented where the couple was willing to deplete their financial resources to achieve a pregnancy with IVF-ET using their own gametes and were eventually successful. CONCLUSIONS: Physicians should restrain from being dogmatic and present all options to patients not merely the physicians' preference. It is embarrassing for a physician to insist that successful pregnancy is impossible only for the patient to prove that physician wrong. After receiving proper data patients should be allowed greater input into their treatment decision. PMID- 22675945 TI - "Embryo glue" does not seem to improve chances of subsequent pregnancy in refractory in vitro fertilization cases. AB - PURPOSE: To determine if the use of Embryo glue improves implantation and pregnancy rates following embryo transfer (ET) in women who failed to conceive in three previous attempts. METHODS: A matched controlled study was performed in women undergoing IVF-ET, donor oocyte recipients and women using their own oocytes having fresh or frozen ETs. A woman having Embryo glue was matched with the very next woman not using glue within six months of age and having the same number of previous failed ETs. RESULTS: Embryo glue did not seem to improve pregnancy or implantation rates. In fact, in evaluating fresh embryo transfers there was a significantly higher live delivered pregnancy rate in the women not using Embryo glue (39.3%) vs those using the glue (14.3%). CONCLUSIONS: Embryo glue does not improve pregnancy outcome in women failing in previous IVF cycles. PMID- 22675946 TI - Predicting ovarian reserve and reproductive outcome using antimullerian hormone (AMH) and antral follicle count (AFC) in patients with previous assisted reproduction technique (ART) failure. AB - PURPOSE OF INVESTIGATION: The main objective of our prospective, observational, analytical research work was to determine whether Anti-Mullerian hormone (AMH) and antral follicle count (AFC) could be effectively used as predictors of ovarian reserve and, possibly, of reproductive outcome with ART. METHODS: We studied 143 IVF/ET cycles in patients with a previous history of ART failure, all of them supposed to be of poor prognosis, who had agreed to another ART attempt after knowing their AMH, AFC, and base hormone (FSH, LH, 17 beta-estradiol) levels. RESULTS: AMH and AFC showed a positive correlation with the number of oocytes retrieved (p = 0.0016) and (p < 0.0001), respectively and with percentage of MII oocytes, (p = 0.00756) and (p < 0.001). The combined use of these markers showed an area under the curve of 82.2% for oocytes retrieved. Our results shows a very high cancelation (22% of started cycles) and very low pregnancy rates (6.7% and 9.8%) in low and normoresponders, respectively. CONCLUSIONS: AMH levels and AFC are reliable indicators of ovarian reserve. Patients with ovarian reserve levels that predict a very low probability of success should be informed that the poor prognosis associated with these values may not justify the expense of IVF/ET. PMID- 22675947 TI - Frequency of subnormal hypoosmotic swelling tests increase with advancing age of the male. AB - PURPOSE: To determine if there is an increased frequency of abnormal hypoosmotic swelling (HOS) tests when testing semen in males of advanced reproductive age. METHODS: Ten-year retrospective review according to six age groups (< or = 29.9, 30-34.9, 35-39.9, 40-44.9, 45.0-49.9, and > or = 50). RESULTS: Compared to males < 35 years old, the frequency of HOS scores < 50% doubles in males 45-49.9 and quadruples in males > or = 50. CONCLUSIONS: Males with low HOS scores despite having no problem with fertilization of the oocytes rarely achieve a pregnancy because of embryo implantation defects unless intracytoplasmic sperm injection (ICSI) is performed. Thus at least one abnormality seen in sperm of males of advanced reproductive age is correctable by performing in vitro fertilization with ICSI. PMID- 22675948 TI - Intracytoplasmic sperm injection completely negates the implantation problem associated with conventional fertilization with sperm with low hypo-osmotic swelling test scores as evidenced by evaluating donor-recipient pairs. AB - PURPOSE: To corroborate or refute the claim that intracytoplasmic sperm injection (ICSI) can overcome the problem found after conventional insemination of oocytes with sperm with low hypoosmotic swelling (HOS) tests of forming embryos with low implantation potential. METHODS: Matched couple pairs sharing one pool of oocytes were identified where one of the male partners had a low HOS test score and the other one with a normal one. Intracytoplasmic sperm injection was always used in those with low HOS test scores (i.e., < 50%) vs ICSI only used for semen abnormalities in the normal HOS group. RESULTS: There were no differences found in either fertilization rates or clinical or live delivered pregnancy rates or implantation rates between these groups. CONCLUSIONS: Intracytoplasmic sperm injection can completely negate the adverse effect that fertilization with sperm with subnormal HOS scores has on embryo implantation potential. PMID- 22675949 TI - Pregnancy outcome following fresh vs frozen embryo transfer into gestational carriers using a simplified slow freeze protocol. AB - PURPOSE: To compare pregnancy rates following fresh vs frozen embryo transfer into gestational carriers. METHODS: Choice of deferring fresh embryo transfer and cryopreserving the embryos vs fresh transfers was not randomized but based on circumstances. The cryopreservation protocol used a simplified slow cool technique avoiding the planar programmable freezer and using a one-step removal of the cryoprotectant. RESULTS: The live delivered pregnancy rate was 51.0% (49/96) for fresh embryo transfer vs 34.3% for transfers of frozen thawed embryos in gestational carriers not having a fresh embryo first. CONCLUSIONS: Using the simplified slow cool cryopreservation protocol with a one-step removal of cryoprotectants pregnancy rates are comparable to what is found in women of similar ages undergoing controlled ovarian hyperstimulation followed by IVF-ET. However, when transferring to a gestational carrier the live delivered pregnancy rates are 50% higher with fresh embryo transfer. PMID- 22675950 TI - The majority of males with subnormal hypoosmotic test scores have normal vitality. AB - PURPOSE: To determine if males with low hypoosmotic swelling (HOS) test scores may have normal vitality tests. METHODS: Retrospective nine-year review of initial semen analyses evaluating vitality and HOS tests. RESULTS: Only 12.5% (45/361) of males with low HOS test scores have low vitality. CONCLUSIONS: WHO seems to treat vitality and HOS as equal tests. We disagree and find that structural defects of the sperm membrane are much less common than functional impairment of the sperm membrane. Since a male with an HOS test score < 50% will rarely achieve a pregnancy with intercourse, intrauterine insemination, or IVF with conventional insemination it is important to check for the HOS test not viability because the HOS test can be easily corrected with ICSI. PMID- 22675951 TI - Immune response and immunotherapy in intraepithelial and invasive lesions of the uterine cervix. AB - Infection with the human papillomavirus virus (HPV) induces innate and acquired immune responses in the cervical stroma, which are a delicate, balanced and generally unpredictable immunological defense. Because of the immunological breaks that the HPV virus causes, eradication of infected cells does not occur, potentially leading to development of intraepithelial and invasive lesions. Advances in our understanding of the immune system and in the definition of antigens in tumor cells has led to many new treatment strategies. As a result, immunotherapy has the potential to be the most specific treatment for tumors, and one that requires elaboration. Recently, immunotherapy with interferon and dendritc cells has been used on intrapepithelial and invasive cervical lesions with promising results. PMID- 22675952 TI - Severe hepatocellular dysfunction in obstetric cholestasis related to combined genetic variation in hepatobiliary transporters. AB - Obstetric cholestasis (OC) is a cholestatic disorder with a prominent genetic background including variation in diverse hepatobiliary lipid transporters, such as ABCB4 (phospholipids) and ABCB11 (bile salts). Given a marked hepatocellular dysfunction in an OC patient indicated by > 40-fold rise in alanine aminotransferase activity and minor gamma-glutamyl transpeptidase increases, we performed genotyping of candidate gene variants associated with adult cholestatic phenotypes. Genetic analysis revealed the heterozygous ABCB4 mutation p.R590Q, the ABCB11 variant p.V444A and the lithogenic ABCG8 variant p.D19H. Aggregation of multiple hepatobiliary transporter variants is rare in OC, and may cooperate to negatively modulate hepatobiliary transport capacities. PMID- 22675953 TI - The effects of benzoylecgonine, oxytocin, ritodrine and atosiban on the contractility of myometrium. An experimental study. AB - PURPOSE: To investigate the response of pregnant and non pregnant rat myometrium to benzoylecgonine, a cocaine metabolite, and oxytocin and to investigate the efficiency of ritodrine and atosiban to overcome the effects of benzoylecgonine and oxytocin. METHODS: Isolation of rat myometrial tissue and recording of contractile activity with isotonic muscle transducer. RESULTS: Benzoylecgonine and oxytocin increase myometrial contractility, while atosiban and ritodrine induce myometrial relaxation. Atosiban was able to revoke the action of oxytocin but not the action of benzoylecgonine. Ritodrine was able to induce muscle relaxation in both oxytocin and benzoylecgonine administration. CONCLUSION: Cocaine metabolites seem to act on the myometrium through different pathways compared with oxytocin. After comparing two widely used tocolytic agents: atosiban and ritodrine, it is indicated that only ritodrine, a beta2 adrenergic receptor agonist, can inhibit the action of cocaine metabolites. This finding indicates that the actions of cocaine on adrenergic mechanisms are responsible to a large part for its effects on myometrium contractility. The use of beta2 adrenergic receptor agonists seems to be preferable for the treatment of myometrial contractions induced by cocaine consumption. PMID- 22675954 TI - Regulation of interleukin-1alpha and tumor necrosis factor-alpha-induced interleukin-8 production by amnion-derived (WISH) cells. AB - PURPOSE OF INVESTIGATION: It has been reported that interleukin (IL)-8 is produced in the amnion and that its production is enhanced by the initiation of labor. The purpose of this study was to clarify the mechanism of IL-8 production by amnion-derived (WISH) cells. METHODS: Cells were cultured and treated with various concentrations of interleukin (IL)-1alpha, IL-1 receptor antagonist (ra), tumor necrosis factor (TNF)- alpha, C2-, C6-ceramide, mitogen-activated protein (MAP) kinase kinase (MEK) inhibitor (U0126) and pyridinyl imidazole (p38 MAP kinase inhibitor, SB203580). IL-8 in the culture medium was measured by ELISA. RESULTS: The production of IL-8 was significantly increased by IL-1alpha or TNF alpha, and the increase of IL-8 stimulated by IL-1alpha was suppressed by IL-1 ra in a dose-dependent manner. The increase in IL-8 production by IL-1alpha or TNF alpha was further enhanced by simultaneous addition of C2-ceramide. The increase of IL-8 stimulated by IL-1alpha or TNF-alpha was also suppressed by treatment with U0126 or SB203580. The results of this study demonstrate that the production of IL-8 induced by IL-1alpha and TNF-alpha is enhanced by C2-ceramide, and suppressed by MEK inhibitor or P38 MAP kinase inhibitor. CONCLUSION: The results suggest that ceramide-mediated accumulation and MAP kinase-mediated suppression of inflammatory events in the amnion may play an important role in the maintenance of pregnancy and initiation of labor. PMID- 22675955 TI - The efficacy of paracetamol versus tenoxicam on postoperative pain and morphine consumption after abdominal hysterectomy: a placebo-controlled, randomized study. AB - OBJECTIVE: The purpose of this study was to determine the analgesic efficacy and side-effects of paracetamol and tenoxicam in comparison with placebo in patients with postoperative pain after elective abdominal hysterectomy. MATERIAL AND METHODS: A total of 120 patients were randomly divided into three groups to receive either paracetamol 1 g, tenoxicam 20 mg or placebo intravenously at the end of surgery, and then morphine was administered by a patient-controlled analgesia device postoperatively. RESULTS: Tenoxicam was associated with lower pain scores at the 2nd, 4th, 6th and 24th hour postoperatively. Total morphine consumption was 44.8 +/- 17.4 mg, 64.6 +/- 19.6 mg, 69.2 +/- 22.1 (tenoxicam, paracetamol and placebo group, respectively) and there was a significant difference in the tenoxicam group compared with the other two groups (p < 0.05). Side-effects except for nausea were similar. CONCLUSION: A single dose of 20 mg tenoxicam provided effective analgesia and reduced total morphine consumption in comparison with paracetamol and placebo after abdominal hysterectomy. PMID- 22675956 TI - Malignant disease as a risk factor for surgical site infection. AB - INTRODUCTION AND OBJECTIVE: Postoperative infections are a great constituent of surgical complications. The most common one is surgical site infection (SSI), as well as vaginal and/or urinary tract infections, infections affecting distant organs and systems and systemic circulation leading to sepsis and septic shock. Our aim was to emphasize the effect of malignant disease on postoperative infection and to establish malignant disease as a risk factor for SSI, per se. MATERIAL AND METHOD: We designed a retrospective study in which 538 women who underwent surgery in the Gynecology and Obstetrics Clinical Center of Serbia during a six-month period in 2009 were analyzed. We collected relevant data regarding SSI incidence (CDC definitions), malignant disease (primary site, type and stage) and other potential risk factors for SSI. We used descriptive statistics, chi-square and Student's t test for comparison of variables with statistical significance atp < 0.05. We also used univariate, multivariate logistic regression and ROC analysis. RESULTS: Surgical site infection was present in 40 patients (7.5%). Univariate analysis revealed that the following factors were significantly related to SSI: age, malignant disease, stage of malignant disease, surgery longer than 120 min, postmenopause, diabetes mellitus, positive preoperative vaginal culture, ASA score and intraoperative blood loss. Multivariate analysis showed that the most important risk factors that contribute to SSI with RR of 4 and 5 are, respectively, FIGO II and FIGO III/IV stage of malignant disease (FIGO II p < 0.05 RR = 4.097; FIGO III/IV < 0.01 RR = 5.061). CONCLUSION: In our study malignant disease erupted as the most important risk factor for SSI. This brings us to question the pathophysiological mechanisms and systemic effects associated with malignant disease. There are few studies discussing the issue of malignancy as an isolated risk factor that 4-5 fold increases the risk of SSIs. It is of utmost interest to define protocols of antimicrobial prophylaxis for gynecological malignancy surgery as are suggested for some other malignancies. PMID- 22675958 TI - Immunohistochemical changes of adenomyosis after heat therapy: comparison of radiofrequency myolysis and endoablation. AB - PURPOSE: To check the pathologic changes of focal adenomyosis after heat therapy using radiofrequency and to evaluate which approach--endometrial ablation or direct heat therapy--is better for adenomyosis. To evaluate whether the timing of the procedure and the menstrual cycle are related to pathologic outcomes after heat therapy. METHODS: This study included nine women who underwent total hysterectomy for adenomyosis (diameter, > or = 6 cm). Six fresh uteri were excised in the midline and subjected to radiofrequency heat therapy at the center of the adenomyomas (direct heat therapy) and three uteri were subjected to endometrial ablation. Thereafter, 1 cm(3) myometrial tissue was obtained at 1 cm, 2 cm, and 3 cm away from the endometrium. Tissue sections were stained with hematoxylin and eosin. Immunohistochemical analysis using antibodies against cytokerain-19 (CK-19), actin, and estrogen receptor/progesterone receptor (ER/PR) was performed to evaluate CK-19 (endometrial epithelium marker), actin (myometrial marker) and ER/PR (checking the state of the menstrual cycle), respectively. RESULTS: After endometrial ablation, cauterized tissues were not noted 2 cm away from the endometrium. All tissues between the endometruim and center of adenomyosis were cauterized after direct heat therapy. During the uterine proliferative phase, unlike the secretory phase, subendometrial layers were cauterized 10 min after direct cauterization. CONCLUSION: Direct heat therapy is more effective than endometrial ablation in adenomyosis, and heat is conducted effectively when the patients are in the proliferative phase. PMID- 22675957 TI - The trend of VEGF-A and PlGF in pregnant patients: a perspective case-control study on 214 women. AB - OBJECTIVE: The aim of this study was to measure plasmatic concentrations of vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PIGF) in pregnant women, and to evaluate their relationship with age, hormonal status, gestational age, and different diseases of pregnancy. METHODS: We selected a control group of 163 patients (96 fertile and 67 in menopause) and a group of 214 pregnant patients during the whole gestational period. VEGF-A and PlGF were assayed by ELISA and EIA methods, respectively. Statistical analysis was performed using the Mann-Whitney test. RESULTS: The control group showed mean VEGF-A and PlGF values of 89.87 pg/ml and 10.22 pg/ml, respectively; PlGF showed the highest values in menopausal patients. The group of pregnant patients showed VEGF-A values of 27.05 pg/ml and PlGF values of 231.36 pg/ml respectively, with lower (for the VEGF-A) and higher (for the PlGF) statistical significance. These values were not influenced by biological age, but were related to gestational age: VEGF-A showed a decrease and PlGF an increase particularly after the 20th gestational week. PlGF showed a statistically significant decrease compared to physiological gestation in spontaneous and threatened abortions (p < 0.0001) and in ectopic pregnancies (p < 0.0001), an increase in ultrasound and CTG alterations (p < 0.05), and threatened premature delivery and uterine hypercontractility (p < 0.01); on the other hand VEGF-A showed a statistically significant increase in ectopic pregnancies (p < 0.05). CONCLUSIONS: VEGF-A and PlGF may play a diagnostic and prognostic role in pregnancy. Further studies are required to better understand the meaning of variability of their values. PMID- 22675959 TI - Risk factors and prevalence of urinary incontinence in postmenopausal women living in Turkey. AB - PURPOSE OF INVESTIGATION: To detect the prevalence, types and risk factors of urinary incontinence (UI) in postmenopausal women. METHODS: Three-hundred and thirty-three patients who were referred to our Menopause Clinic between August 2008 and May 2009 were included in the study according to the acceptance criteria. A detailed questionnaire was completed by the patients who were between 31-65 years of age. RESULTS: The mean age was 52.5 and the mean age at which menopause symptoms started was 45.8. The prevalence of urinary incontinence was found to be 45.6%. The most frequently seen UI type was mixed urinary incontinence (68.4%). Advanced age, vaginal delivery, high BMI and no hormone replacement therapy were regarded as significant risk factors. CONCLUSION: UI is a common problem influencing the social experience of postmenopausal women. The prevalence of UI was detected as 45.6% in our study. The quality of life in postmenopausal women can be augmentated by diagnosing the risk factors of UI and making an effort to improve the condition. PMID- 22675960 TI - Comparison of propofol/ketamine versus propofol/alfentanil for dilatation and curettage. AB - BACKGROUND AND OBJECTIVES: The use of propofol with an analgesic agent is probably the principal technique for the induction of anesthesia for dilatation and curettage (D&C) at the present time. We designed a randomized, double-blind study to compare the clinical efficacy of ketamine and alfentanil when combined with propofol for short-lasting anesthesia during D&C. METHODS: The study included 60 patients scheduled for D&C. Either alfentanil 10 microg/kg(-1) IV (Group A) or ketamine 0.5 mg/kg(-1) IV (Group K) were given to each patient with propofol 0.7 mg/kg(-1) IV for anesthesia induction. Surgeon and patient satisfaction, Aldrete score, Verbal Pain Scale rating, total propofol dose, orientation time, and adverse events such as bradycardia, hypotension, nausea, and vomiting were evaluated. RESULTS: In Group A orientation time was significantly shorter and propofol consumption significantly lower than in Group K. CONCLUSIONS: Both alfentanil/propofol and ketamine/propofol combinations provide reliable and effective hypnosis and analgesia; however, the ketamine/propofol combination leads to higher consumption of propofol and results in a longer orientation time than the alfentanil/propofol combination. PMID- 22675961 TI - Removal of uterine fibroids during cesarean section: a difficult therapeutic decision. AB - PURPOSE OF INVESTIGATION: Myoma excision during cesarean delivery has traditionally been discouraged, however controversy persists among studies of myomectomy being performed during cesarean section. In this study, medical records of patients who underwent cesarean section our institution were evaluated retrospectively. METHODS: A total of 70 cases of cesarean myomectomy done during this period were included (group 1) and compared with the patients who underwent cesarean section alone (group 2). RESULTS: Mean surgical time of the myomectomy group was 58.1 +/- 23 minutes which was significantly increased (p < 0.01). Mean postoperative hemoglobin value was 9.6 +/- 1.5 in the myomectomy group and 10.8 +/- 1.01 in controls (p = 0.01). Length of hospital stay was significantly longer in the myomectomy group (p < 0.05). CONCLUSION: This study shows that myomectomy during cesarean section is a feasible procedure without any serious complications. The procedure is related with increased blood loss that does not require blood transfusion. PMID- 22675963 TI - Magnetic resonance hysterosalpingography in the evaluation of tubal patency in infertile women: an observational study. AB - The purpose of this study was to evaluate the ability of magnetic resonance hysterosalpingography (MR-HSG) to demonstrate fallopian tube patency in infertile women and to improve the MR-HSG technique. Sixteen consecutive infertile women were recruited for this trial. All subjects underwent clinically indicated MR HSG: 10-15 ml of 1:10 solution of gadolinium and normal sterile saline (0.9%) was gently hand-injected intracervically through a 7 French balloon catheter while seven consecutive flash-3D dynamic (FL 3D DY) T1-weighted MR sequences were acquired. Two readers independently assessed image quality as well as anatomic and pathologic correlations. Patient comfort was evaluated using a specific score questionnaire. MR-HSG was successfully completed in all patients. In 14/16 (87.4%) patients, MR-HSG showed bilateral tubal patency with symmetric contrast agent diffusion and a regular tubo-ovarian relationship. One patient (6.3%) with monolateral hydrosalpinx presented no contrast agent diffusion in the affected side (monolateral tubal occlusion); in another patient (6.3%) the fallopian tube was displaced upward causing loss of the tubo-ovarian anatomical relationship resulting in asymmetric and inadequate contrast agent diffusion. Eight women (50%) were found to have abnormalities on MR imaging; these abnormalities included multi follicular ovaries (5 cases 31.1%), endometrioma (1 case, 6.3%), leiomyoma (1 case/6.3%) and endometrial polyp (1 case/6.3%). The average time required for the study was 25-30 minutes. Analysis of the questionnaires administered to the patients showed that 15/16 patients (93.7%) were fully satisfied with the procedure. All examinations were judged to be of high diagnostic quality and the two readers made similar diagnoses. In conclusion, MR HSG is a feasible, useful and well tolerated tool for the assessment of the uterus, fallopian tubes, ovaries and extra-uterine structures. MR-HSG is a new promising imaging approach to female infertility. PMID- 22675962 TI - The impact of HPV diagnosis on women's sexual and mental health: preliminary findings. AB - PURPOSE OF INVESTIGATION: The objective of the present study was to demonstrate the impact of HPV diagnosis on sexual function and mental health of Greek women. METHODS: The study population included 51 patients who proceeded to the gynecological outpatient clinic of "Aretaieion" Hospital, Athens, during 2008 2009. The participants were asked to complete a questionnaire regarding demographic characteristics, knowledge on HPV, gynecological and sexual history, as well as questions regarding their mental and sexual health after the diagnosis. RESULTS: Mean age of the participants was 36 years and mean age of their first Pap smear test was 24.4 years. Mean age of HPV diagnosis was 34 years and mean number of sexual partners was four. Regarding mental health, the majority experienced anxiety after the HPV diagnosis as well as fear regarding their health in the future. Nearly half of the women experienced guilt and anger and some of them distress, shame, diminution of self-esteem and stigmatization. Diminution in the level of sexual interest and desire and decrease in sexual intercourse frequency were quite often reported. CONCLUSION: Except for the important physical impact of HPV infection, its diagnosis seems to trigger several negative feelings and reduce sexual desire. PMID- 22675965 TI - Molecular diagnosis of CMV infection in fetal aborted tissues in the region of Thrace. AB - PURPOSE: To detect the incidence of CMV infection in spontaneous abortion in Thrace. METHODS: Genetic material from 143 fetuses aged from 11 to 39 weeks was examined. The material originated from various regions of Thrace. All fetuses and the respective placentas underwent routine histopathology. DNA was isolated from sections of paraffinized tissues. Detection of CMV in the DNA genomic samples was performed using a commercial PCR-based detection kit. RESULTS: From the 143 fetuses that were examined, two were found to be CMV positive. Pathological findings related to inflammatory corruptions were observed in the placentas of 97 embryos, including the CMV infected ones. CONCLUSIONS: This study indicates CMV DNA infection in 1.4% of aborted fetuses. CMV infection incidence in aborted fetuses is similar to this reported in other European regions. The molecular technique of PCR applied on paraffin-embedded biopsy material is proven to be an accurate, valid and fast method for investigating the CMV infection in aborted fetuses. PMID- 22675964 TI - Effects of methylene blue, pentoxyphylline and enoxaparin on postoperative adhesion formation and markers of angiogenesis in a rat uterine horn model. AB - OBJECTIVE: Postoperative adhesions still remain as a common and serious problem leading to morbidity, mortality and economic loss. Adhesions are the major cause of postoperative intestinal obstruction, infertility, and chronic pelvic pain. In this study, we aimed to compare adhesion prevention effects of pentoxyphylline, enoxaparin and methylene blue and to investigate the effects of these agents on angiogenesis, which is suggested as an important step in wound healing, in rat a uterine horn model. MATERIAL AND METHODS: Forty female Wistar albino rats were randomized into four subgroups and underwent laparotomy. Adhesions developed following cauterization at the anti-mesenteric surfaces of both uterine horns. After 14 days, adhesions were investigated by using macroscopic, histopathological and immunohistochemical [vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming growth factor (TGF beta), platelet-derived growth factor (PDGF)] methods. RESULTS: We found that enoxaparin significantly reduced adhesion formation. Pentoxyphylline had no significant effect on adhesion formation, whereas methylene blue had a significant decreasing effect on histopathologically determined adhesion markers and it may affect angiogenesis through PDGF. CONCLUSION: Among three agents, which were intraperitoneally given by a single dose manner in order to prevent postoperative adhesions, methylene blue and enoxaparin exhibited a positive effect, while no such effect was shown with pentoxyphylline. PMID- 22675966 TI - Examination of the effect of melatonin use in Pomeroy method of tubal ligation on ovarian histology in rats. AB - OBJECTIVE: To examine the effects of melatonin use in the unilateral Pomeroy method of tubal ligation on ovarian histology in rats. SETTING: Firat University Medical School, Obstetrics and Gynecology Department, Elazig. MATERIAL AND METHOD: Thirty adult, female rats of Wistar albino species with regular cycles were randomly allocated to three groups in the estrus phase: G1 (n: 10): The abdomen was opened and closed. G2 (n: 10): The group where the abdomen was opened, and the Pomeroy method of tubal ligation was performed. G3 (n: 10): The group where the abdomen was opened, and Pomeroy method of tubal ligation was performed 15 min after 10 mg/kg/ip melatonin administration. Abdomens of all rats were opened six months later and left oophorectomy was performed. Samples of the left ovary were fixed in formaldehyde. The preparations were stained with hematoxylin eosin, and primordial, primary, secondary and tertiary follicles were counted. All the numbers were added up to determine the ovarian follicle reserve. An atretic follicle count was made. The corpus luteum and corpus albicans were counted, and the number of total corpuses were calculated. Regression of angiogenesis within the corpus luteum was examined. Presence of fibrosis on ovarian stroma was examined. An ordinal scale was formed for the regression of angiogenesis within the corpus luteum and presence of fibrosis (none: 0p, present: 1p, markedly present: 2). Follicle cysts in the ovary were counted. Kruskal Wallis variance analysis was used in the statistical analysis of data; p < 0.05 were considered significant. RESULTS: The comparison between G1 and G3 showed that all values were similar (p > 0.05, Kruskal Wallis variance analysis). When G2 was compared with G1 and G3, regression of angiogenesis in the corpus luteum was found to be significantly lower (p < 0.05, Mann Whitney U test), while atretic follicle count and fibrosis were significantly higher in G2 (p < 0.05, Mann Whitney U test). CONCLUSION: The Pomeroy method of tubal ligation reduces regression of angiogenesis in the corpus luteum, and increases atretic follicles and fibrosis development. Melatonin use restores these harmful effects. Melatonin can be used to refrain from this negative effect of the Pomeroy method of tubal ligation on the ovary. PMID- 22675967 TI - Effect of fibrin glue and comparison with suture on experimental induction of endometriosis in a rat endometrial autograft model. AB - OBJECTIVE: The effects of fibrin glue (FG) and suture were investigated and compared with experimental induction in an endometriosis model. MATERIAL AND METHODS: A randomized, controlled, and double-blind study was performed with 25 adult female Wistar Albino rats. Two autologous endometrial grafts were obtained from each of the rats. The endometrial grafts were transplanted by gluing with FG on the right abdominal wall and suturing with only 5/0 prolene on the left in ten rats. Gluing+suturing and after suturing over the covering with FG of the endometrial graft were performed, respectively, on the right and left in another ten rats. Covering with FG glue of the endometrial graft was performed in another five rats. The endometriosis-like lesions and intraperitoneal adhesions were evaluated macroscopically and histopathologically. RESULTS: The mean volume (31.4 +/- 17.3), adhesion (0.8 +/- 0.7) and inflammatory reaction (1.2 +/- 0.7) score of the implants in the group using only FG were significantly lower than in the group using suture [respectively, (49.2 +/- 20.6), (2.4 +/- 0.8), (2.2 +/- 0.8)] (p < 0.05). CONCLUSIONS: Our results demonstrate the general feasibility of reproducible and reliable endometrial graft fixation with FG onto the inner abdominal surface in rats. Furthermore, several advantageous characteristics could be demonstrated such as less inflammation and fewer adhesions. PMID- 22675968 TI - Comparison of diclofenac sodium with indomethacin suppositories for mediolateral episiotomies. AB - OBJECTIVE: The study was carried out to compare the analgesic effect of diclofenac sodium and indomethacin suppositories for management of right mediolateral episiotomy repair. METHOD: A total of 70 patients who gave birth vaginally with right mediolateral episitomy were randomly assigned to receive 100 mg diclofenac sodium suppositories/day (G1, n = 35) or 100 mg indomethacin supposotories/day (G2, n = 35) after episiotomy repair and postpartum for three days. Pain ratings were recorded before, the first hour and 24 hours after medication. The verbal rating scale (VRS) and visual analog scale (VAS) were used for pain recording. The independent T test, Mann-Whitney U and Wilcoxon rank test were used for statistical analysis and Spearman correlation analysis was used for comparison between VRS and VAS. RESULTS: Diclofenac sodium was a more effective analgesic than indomethacin suppositories for right mediolateral episiotomy pain. For G1 the first hour VRS was 2.6 +/- 0.5 points and VAS 4.9 +/- 0.8 points; for G2 the first hour VRS was 3.4 +/- 0.6 points VAS 6.6 +/- 1.2 points; this difference was statistically significant (p < 0.05, Mann-Whitney U test). For G1 at the 24th hour VRS was 1.2 +/- 0.4 points and VAS 2.4 +/- 0.9 points; for G2 at the 24th hour VRS was 2 +/- 0.7 points and VAS was 3.4 +/- 1.3 points; the difference was statistically significant (p < 0.05, Mann-Whitney U test). The first and 24th hour pain scores (VAS1-VAS24, VRS1-VRS24) were decreased dramatically for both groups (p < 0.05, Wilcoxon rank test). A positive correlation was obtained between the first and 24th hour VRS and VAS by Spearman correlation analysis (r(s) = 0.9, n = 70, p = 0.000). CONCLUSION: The two analgesics were effective after episiotomy repair, however diclofenac sodium suppositories may be the preferred choice because they were more effective. PMID- 22675969 TI - Early abdominal pregnancy with an unexpected and misleading location. The ultrasonographic interpretation. AB - Abdominal pregnancy is a rare condition defined as an ectopic pregnancy that implants in the peritoneal cavity and is associated with important morbidity and mortality. We report a case of a 35-year-old woman with an ultrasonographic diagnosis of a left extrauterine pregnancy located proximally in the isthmus or distally in the interstitial region. In the exploratory laparotomy a gestational sac implanted anteriorly on the uterine serosa was found, with no signs of uterine perforation or tubal abortion. The pathologic examination confirmed the diagnosis of an early first trimester abdominal pregnancy. This case illustrates the importance of an early sonography in the diagnosis of an abdominal pregnancy as well as a high index of suspicion. PMID- 22675970 TI - First trimester diagnosis of 13q-syndrome associated with increased fetal nuchal translucency thickness. Clinical findings and systematic review. AB - 13q-syndrome is a rare chromosomal disorder caused by partial deletion of the long arm of chromosome 13 with variable phenotypic presentation. Further sonographic features involve fetal growth restriction, bradycardia, encephalocele, facial dysmorphism and upper extremity deformity. We report a case of 13q-syndrome presenting as increased nuchal translucency diagnosed by chromosome studies and confirmed by array comparative genomic hybridization (CGH) analysis in the first trimester of pregnancy. Pregnancy was terminated at 14 weeks' gestation. The parents did not give consent for a postmortem examination. Furthermore we performed a systematic review of the international literature on previous cases of 13q-syndrome diagnosed prenatally. Our case emphasizes the importance of a detailed 11-14 week ultrasound assessment in diagnosing fetal chromosomal aberrations in combination with the modern aspects of array CGH, thus providing more precise and rapid prenatal diagnosis. PMID- 22675971 TI - Complicated abdominal hysterectomy subsequent to uterine embolization for large fibroids. AB - Uterine artery embolization (UAE) has increasingly been offered as a safe alternative method for treating uterine fibroids with major symptoms. By this technique patients could avoid surgical cure or definite treatment such as hysterectomy. UAE decreases the uterine blood supply to the tissues and this might predispose to intraabdominal adhesion formation as a result of tissue necrosis. A case of a complicated routine hysterectomy due to strong adhesions found intraabdominally during surgery is reported. Our patient had no predisposing factors for adhesions, but she had undergone UAE one year earlier for large fibroids and decided to proceed to surgical therapy when symptoms returned. PMID- 22675972 TI - Removal of a large bizarre uterine leiomyoma by operative hysteroscopy. Case report and review of the literature. AB - BACKGROUND: Atypical leiomyomas are relatively uncommon in the general practice of gynaecology. We present a case of a large uterine bizarre leiomyoma removed by operative hysteroscopy and review of the literature. CASE: The patient, a 49-year old, gravida 3, para 3, perimenopausal Greek woman presented to our Department because of dysmenorrhea and abnormal vaginal bleeding. She underwent hysteroscopy in which a large submucosal leiomyoma was detected and entirely removed in one session. The histopathology revealed bizarre uterine leiomyoma. DISCUSSION: There is no evidence to indicate that hysterectomy is necessary, if the diagnosis of atypical leiomyoma has been firmly established. PMID- 22675974 TI - Dionex corporation. PMID- 22675973 TI - Pancreatic cancer with liver metastases in a pregnant patient: case report and review of the literature. AB - In this case report, the authors discuss clinical presentation, surgical procedure and early results of chemotherapy of pancreatic carcinoma with liver metastases diagnosed a few days after delivery. Pancreatic adenocarcinoma occurs infrequently in pregnant and childbearing women: only ten cases have been reported in the literature. The early diagnosis of pancreatic cancer is difficult because symptoms appear when cancer is about to reach an advanced stage. In pregnancy, it is even more difficult because symptoms like dyspepsia, vomiting and epigastric pain may result confusing. The authors outline the difficulties in diagnosis and treatment of this kind of disease during pregnancy. PMID- 22675975 TI - Science & technology integration, inc. PMID- 22675977 TI - Recycled post leachability. PMID- 22675978 TI - Dioxins form on collected particles. PMID- 22675979 TI - Degrading olive mill wastes. PMID- 22675980 TI - Wastewater treatment. PMID- 22675981 TI - Soil mineralization. PMID- 22675983 TI - Acs publications. PMID- 22675982 TI - Reducing fugitive vapors. PMID- 22675985 TI - Preserving metal samples. PMID- 22675984 TI - Explosives composting. PMID- 22675986 TI - Surface water. PMID- 22675987 TI - Dam deconstruction. PMID- 22675988 TI - Drilling wastes do not slow bioremediation. PMID- 22675989 TI - TCE desorption rates in soil. PMID- 22675990 TI - Acs publications. PMID- 22675991 TI - Sludge stabilization effects. PMID- 22675992 TI - Pulp mill effluent toxicity. PMID- 22675993 TI - Absorbent plastic biofilters. PMID- 22675994 TI - EPA "devolution" urged. PMID- 22675995 TI - EPA turns to states for MACT rules. PMID- 22675997 TI - Voluntary drinking-water program established. PMID- 22675996 TI - Enhanced air monitoring delayed again. PMID- 22675999 TI - Absolute standards. PMID- 22675998 TI - Clean air operating programs. PMID- 22676000 TI - House passes Clean Water Act; opposition expected in Senate. PMID- 22676001 TI - Highlights of h.R. 961. PMID- 22676002 TI - Clinton releases enviro-tech plan. PMID- 22676003 TI - Study endorses EMAP environmental trends sampling method. PMID- 22676004 TI - Cryptosporidium analytical method fails round-robin test. PMID- 22676005 TI - Consortiumto verify site characterization technologies. PMID- 22676006 TI - EPA's Environmental Leadership Program. PMID- 22676007 TI - EPA, leading companies join in pilot management program. PMID- 22676008 TI - Manufacturers, EPA try to consolidate CAA rules. PMID- 22676009 TI - Climate convention agrees to set new greenhouse gas limits. PMID- 22676010 TI - Illinois to establish VOC emissions-trading market. PMID- 22676011 TI - DOE projects little savings from new cleanup technology. PMID- 22676012 TI - Sierra Club strikes back at Congress. PMID- 22676013 TI - Tough times predicted for remediation industry. PMID- 22676014 TI - ACS approves undergraduate environmental chemistry program. PMID- 22676015 TI - Mexico City aquifer depletion degrading water quality. PMID- 22676016 TI - Briefs. PMID- 22676017 TI - When is lead a health risk? PMID- 22676019 TI - Up in smoke: The air pollution control market. PMID- 22676018 TI - Selling blue skies, clean water. PMID- 22676020 TI - China strives to make the polluter pay. PMID- 22676021 TI - Hardwood(r). PMID- 22676022 TI - Digging deep. PMID- 22676023 TI - American chemical society. PMID- 22676024 TI - Cambridge isotope laboratories. PMID- 22676026 TI - Viking instruments corporation. PMID- 22676025 TI - Analytical products. PMID- 22676027 TI - Acs publications. PMID- 22676029 TI - The 11th annual waste testing and quality assurance symposium. PMID- 22676030 TI - ES&T Information. PMID- 22676031 TI - The ammcon chemical society. PMID- 22676032 TI - National university of singapore. PMID- 22676033 TI - Classified section. PMID- 22676034 TI - American chemical society. PMID- 22676035 TI - Acs publications. PMID- 22676036 TI - Professional consultants services directory. PMID- 22676037 TI - Correction to Design of Bcl-2 and Bcl-xL Inhibitors with Subnanomolar Binding Affinities Based upon a New Scaffold. PMID- 22676039 TI - Microplastic in terrestrial ecosystems and the soil? PMID- 22676038 TI - Hyperdopaminergic modulation of inhibitory transmission is dependent on GSK-3beta signaling-mediated trafficking of GABAA receptors. AB - Cortical dopamine (DA) modulation of the gamma-amino butyric acid (GABA) system is closely associated with cognitive function and psychiatric disorders. We recently reported that the glycogen synthase kinase 3beta (GSK-3beta) pathway is required for hyperdopamine/D2 receptor-mediated inhibition of NMDA receptors in the prefrontal cortex. Here we explore whether or not GSK-3beta is also involved in dopaminergic modulation of GABAA receptor-mediated inhibitory transmission. We confirmed that DA induces a dose-dependent, bidirectional regulatory effect on inhibitory postsynaptic currents (IPSCs) in prefrontal neurons. The modulatory effects of DA were differentially affected by co-application of GSK-3beta inhibitors and different doses of DA. GSK-3beta inhibitors completely blocked high-dose (20 MUM) DA-induced depressive effects on IPSCs but exhibited limited effects on the facilitating regulation of IPSC in low-dose DA (200 nM). We also confirmed that surface expressions of GABAA receptor beta2/3 subunits were significantly decreased by DA applied in cultured prefrontal neurons and in vivo administration of DA reuptake inhibitor. These effects were blocked by prior administration of GSK-3beta inhibitors. We explored DA-mediated regulation of GABAA receptor trafficking and exhibited the participation of brefeldin A inhibited GDP/GTP exchange factor 2 (BIG2) or dynamin-dependent trafficking of GABAA receptors. Together, these data suggest that DA may act through different signaling pathways to affect synaptic inhibition, depending on the concentration. The GSK-3beta signaling pathway is involved in DA-induced decrease in BIG2 dependent insertion and an increase in the dynamin-dependent internalization of GABAA receptors, which results in suppression of inhibitory synaptic transmission. PMID- 22676040 TI - Recognition of Hg2+ ion through restricted imine isomerization: crystallographic evidence and imaging in live cells. AB - A newly synthesized imine-based receptor (L) showed remarkable specificity toward the Hg(2+) ion in aqueous media over other metal ions. Coordination of L to Hg(2+) induces a turn-on fluorescence response. This was explained based on the restricted imine isomerization along with PET on coordination to Hg(2+). X-ray structural evidence tends to favor a C-C bond rotation rather than C?N isomerization for adopting a favorable conformation in L for coordination to Hg(2+). This reagent could be used for imaging the accumulation of Hg(2+) ions in HeLa cells. PMID- 22676041 TI - Synthesis of few-layer GaSe nanosheets for high performance photodetectors. AB - Two-dimensional (2D) semiconductor nanomaterials hold great promises for future electronics and optics. In this paper, a 2D nanosheets of ultrathin GaSe has been prepared by using mechanical cleavage and solvent exfoliation method. Single- and few-layer GaSe nanosheets are exfoliated on an SiO(2)/Si substrate and characterized by atomic force microscopy and Raman spectroscopy. Ultrathin GaSe based photodetector shows a fast response of 0.02 s, high responsivity of 2.8 AW( 1) and high external quantum efficiency of 1367% at 254 nm, indicating that the two-dimensional nanostructure of GaSe is a new promising material for high performance photodetectors. PMID- 22676042 TI - Lipase applications in oil hydrolysis with a case study on castor oil: a review. AB - Lipase (triacylglycerol acylhydrolase) is a unique enzyme which can catalyze various types of reactions such as hydrolysis, esterification, alcoholysis etc. In particular, hydrolysis of vegetable oil with lipase as a catalyst is widely studied. Free lipase, lipase immobilized on suitable support, lipase encapsulated in a reverse micelle and lipase immobilized on a suitable membrane to be used in membrane reactor are the most common ways of employing lipase in oil hydrolysis. Castor oil is a unique vegetable oil as it contains high amounts (90%) of a hydroxy monounsaturated fatty acid named ricinoleic acid. This industrially important acid can be obtained by hydrolysis of castor oil. Different conventional hydrolysis processes have certain disadvantages which can be avoided by a lipase-catalyzed process. The degree of hydrolysis varies widely for different lipases depending on the operating range of process variables such as temperature, pH and enzyme loading. Immobilization of lipase on a suitable support can enhance hydrolysis by suppressing thermal inactivation and estolide formation. The presence of metal ions also affects lipase-catalyzed hydrolysis of castor oil. Even a particular ion has different effects on the activity of different lipases. Hydrophobic organic solvents perform better than hydrophilic solvents during the reaction. Sonication considerably increases hydrolysis in case of lipolase. The effects of additives on the same lipase vary with their types. Nonionic surfactants enhance hydrolysis whereas cationic and anionic surfactants decrease it. A single variable optimization method is used to obtain optimum conditions. In order to eliminate its disadvantages, a statistical optimization method is used in recent studies. Statistical optimization shows that interactions between any two of the following pH, enzyme concentration and buffer concentration become significant in presence of a nonionic surfactant named Span 80. PMID- 22676043 TI - Pulsed ESR dipolar spectroscopy for distance measurements in immobilized spin labeled proteins in liquid solution. AB - Pulsed electron spin resonance (ESR) dipolar spectroscopy (PDS) in combination with site-directed spin labeling is unique in providing nanometer-range distances and distributions in biological systems. To date, most of the pulsed ESR techniques require frozen solutions at cryogenic temperatures to reduce the rapid electron spin relaxation rate and to prevent averaging of electron-electron dipolar interaction due to the rapid molecular tumbling. To enable measurements in liquid solution, we are exploring a triarylmethyl (TAM)-based spin label with a relatively long relaxation time where the protein is immobilized by attachment to a solid support. In this preliminary study, TAM radicals were attached via disulfide linkages to substituted cysteine residues at positions 65 and 80 or 65 and 76 in T4 lysozyme immobilized on Sepharose. Interspin distances determined using double quantum coherence (DQC) in solution are close to those expected from models, and the narrow distance distribution in each case indicates that the TAM based spin label is relatively localized. PMID- 22676044 TI - Intrinsic thermodynamics of ethoxzolamide inhibitor binding to human carbonic anhydrase XIII. AB - BACKGROUND: Human carbonic anhydrases (CAs) play crucial role in various physiological processes including carbon dioxide and hydrocarbon transport, acid homeostasis, biosynthetic reactions, and various pathological processes, especially tumor progression. Therefore, CAs are interesting targets for pharmaceutical research. The structure-activity relationships (SAR) of designed inhibitors require detailed thermodynamic and structural characterization of the binding reaction. Unfortunately, most publications list only the observed thermodynamic parameters that are significantly different from the intrinsic parameters. However, only intrinsic parameters could be used in the rational design and SAR of the novel compounds. RESULTS: Intrinsic binding parameters for several inhibitors, including ethoxzolamide, trifluoromethanesulfonamide, and acetazolamide, binding to recombinant human CA XIII isozyme were determined. The parameters were the intrinsic Gibbs free energy, enthalpy, entropy, and the heat capacity. They were determined by titration calorimetry and thermal shift assay in a wide pH and temperature range to dissect all linked protonation reaction contributions. CONCLUSIONS: Precise determination of the inhibitor binding thermodynamics enabled correct intrinsic affinity and enthalpy ranking of the compounds and provided the means for SAR analysis of other rationally designed CA inhibitors. PMID- 22676045 TI - Peer-led diabetes self-management programme for community-dwelling older people in China: study protocol for a quasi-experimental design. AB - AIM: A protocol for a new peer-led self-management programme for community dwelling older people with diabetes in Shanghai, China. BACKGROUND: The increasing prevalence of type 2 diabetes poses major public health challenges. Appropriate education programmes could help people with diabetes to achieve self management and better health outcomes. Providing education programmes to the fast growing number of people with diabetes present a real challenge to Chinese healthcare system, which is strained for personnel and funding shortages. Empirical literature and expert opinions suggest that peer education programmes are promising. DESIGN: Quasi-experimental. METHODS: This study is a non equivalent control group design (protocol approved in January, 2008). A total of 190 people, with 95 participants in each group, will be recruited from two different, but similar, communities. The programme, based on Social Cognitive Theory, will consist of basic diabetes instruction and social support and self efficacy enhancing group activities. Basic diabetes instruction sessions will be delivered by health professionals, whereas social support and self-efficacy enhancing group activities will be led by peer leaders. Outcome variables include: self-efficacy, social support, self-management behaviours, depressive status, quality of life and healthcare utilization, which will be measured at baseline, 4 and 12 weeks. DISCUSSION: This theory-based programme tailored to Chinese patients has potential for improving diabetes self-management and subsequent health outcomes. In addition, the delivery mode, through involvement of peer leaders and existing community networks, is especially promising considering healthcare resource shortage in China. PMID- 22676046 TI - Transcriptome analysis of the citrus red mite, Panonychus citri, and its gene expression by exposure to insecticide/acaricide. AB - The citrus red mite, Panonychus citri, is known for its ability rapidly to evolve resistance to insecticides/acaricides and to adapt to hosts that produce toxins. In this study, we constructed an unprecedented four gigabase pair transcriptome of P. citri, which was assembled into 64 149 unique transcripts, the functions of which were annotated by five public databases. A total of 116 unique transcripts were identified as representatives of potential involvement in the detoxification of xenobiotics. Genes recorded to encoding insecticide/acaricide target proteins were also obtained from the P. citri transcriptome. In order to explore novel candidate genes potentially involved in the pesticide detoxification of P. citri, we also constructed digital gene expression libraries of short-term transcriptome responses of P. citri to pesticides, which resulted in the identification of 120 unique transcripts potentially associated with insecticide/acaricide detoxification. Our study will facilitate molecular research on pesticide resistance in citrus red mites, as well as in other phytophagous mites. PMID- 22676047 TI - High prevalence of exon 8 G533C mutation in apparently sporadic medullary thyroid carcinoma in Greece. AB - OBJECTIVE: Genetic screening for ret mutation has become routine practice in the evaluation of medullary thyroid carcinoma (MTC). Approximately 25% of these tumours are familial, and they occur as components of the multiple endocrine neoplasia type 2 syndromes (MEN 2A and 2B) or familial MTC. In familial cases, the majority of mutations are found in exons 10, 11, 13, 14 or 15 of the ret gene. A rare mutation involving exon 8 (G533C) has recently been reported in familial cases of MTC in Brazil and Greece; some of these cases were originally thought to be sporadic. The aim of this study was to re-evaluate a series of sporadic cases of MTC, with negative family history, and screen them for germline mutations in exon 8. DESIGN AND PATIENTS: Genomic DNA was extracted from peripheral lymphocytes in 129 unrelated individuals who had previously been characterized as 'sporadic' based on the negative family history and negative screening for ret gene mutations. Samples were analysed in Applied Biosystems 7500 real-time PCR and confirmed by sequencing. MEASUREMENTS AND RESULTS: The G533C exon 8 mutation was identified in 10 of 129 patients with sporadic MTC. Asymptomatic gene carriers were subsequently identified in other family members. CONCLUSION: In our study, we found that 7.75% patients with apparently sporadic MTC do carry G533C mutation involving exon 8 of ret. We feel that there is now a need to include exon 8 mutation screening in all patients diagnosed as sporadic MTC, in Greece. PMID- 22676048 TI - Persistent pain, sensory disturbances and functional impairment after adjuvant chemotherapy for breast cancer: cyclophosphamide, epirubicin and fluorouracil compared with docetaxel + epirubicin and cyclophosphamide. AB - BACKGROUND: Taxanes used in adjuvant therapy for breast cancer are neurotoxic, and thereby being a potential risk factor for persistent pain after breast cancer treatment (PPBCT) and sensory disturbances. The purpose was to compare patients treated with cyclophosphamide, epirubicin and fluorouracil (CEF) and cyclophosphamide and epirubicin + docetaxel (CE + T) in relation to PPBCT, sensory disturbances, peripheral sensory disturbances and functional impairment. MATERIAL AND METHODS: A comparative nationwide cross-sectional questionnaire study on two cohorts treated with CEF respectively CE + T, based on the Danish Breast Cancer Cooperative Groups database. INCLUSION CRITERIA: women treated with chemotherapy as adjuvant treatment for primary breast cancer, age 18-69 years, without recurrence. RESULTS: One thousand two hundred and forty-one patients allocated to CEF in 2005-2006 and 1652 patients allocated to CE + T in 2007-2008 were included. Six hundred and sixty-four (53%) with CEF and 861 (53%) patients with CE + T reported pain. In the multivariate analysis including available risk factors, CE + T did not confer an increased risk of PPBCT, OR 0.95 (95% CI 0.81 1.11), p = 0.52, compared to CEF. Patients treated with CE + T had a lower risk of sensory disturbances in the area of surgery compared with CEF, OR 0.75 (95% CI 0.62-0.90), p = 0.002. More CE + T patients reported peripheral sensory disturbances in the hands, OR 1.56 (95%CI 1.27-1.92), p < 0.0001, and in the feet, OR 2.0 (95% CI 1.66-2.42) p < 0.0001, compared to CEF. There was no difference in functional impairment (p = 0.62). CONCLUSION: Docetaxcel as adjuvant treatment for breast cancer does not increase the risk of PPBCT, sensory disturbances in the surgical area or functional impairment, but increase risk for peripheral sensory disturbances. PMID- 22676049 TI - Monitoring dynamic reactions of red blood cells to UHF electromagnetic waves radiation using a novel micro-imaging technology. AB - Multiple state-of-the-art techniques, such as multi-dimensional micro-imaging, fast multi-channel micro-spetrophotometry, and dynamic micro-imaging analysis, were used to dynamically investigate various effects of cell under the 900 MHz electromagnetic radiation. Cell changes in shape, size, and parameters of Hb absorption spectrum under different power density electromagnetic waves radiation were presented in this article. Experimental results indicated that the isolated human red blood cells (RBCs) do not have obviously real-time responses to the ultra-low density (15 MUW/cm(2), 31 MUW/cm(2)) electromagnetic wave radiation when the radiation time is not more than 30 min; however, the cells do have significant reactions in shape, size, and the like, to the electromagnetic waves radiation with power densities of 1 mW/cm(2) and 5 mW/cm(2). The data also reveal the possible influences and statistical relationships among living human cell functions, radiation amount, and exposure time with high-frequency electromagnetic waves. The results of this study may be significant on protection of human being and other living organisms against possible radiation affections of the high-frequency electromagnetic waves. PMID- 22676050 TI - The effect of camera location on observation-based posture estimation. AB - This study used the observation-based method showing images on computer to evaluate angle estimation errors of 8 body segments in 3 motion planes at up to 28 segment angles and 5 camera locations with respect to goniometric measurements. Thirty observers participated in evaluating segment angles. Forearm (9.9 degrees ) and thigh (9.5 degrees ) had smaller errors than hand (14.0 degrees ) and foot had the smallest error (8.7 degrees ) due to its narrow range of motion (ROM). Errors were small with camera locations perpendicular to motions in the planes, such as 90 degrees camera location for the flexion and extension of arm (6.3 degrees ), forearm (7.9 degrees ), thigh (6.5 degrees ), and leg (8.1 degrees ) in the sagittal plane. Segments had small errors of 3.1 degrees , 4.6 degrees , and 3.8 degrees at segment angles of -90 degrees , 0 degrees and 90 degrees , respectively. Care should be taken when estimating angles by the observation-based method for a specific segment motion and viewing direction is suggested to be perpendicular to the motion plane. PRACTITIONER SUMMARY: Some companies may not allow many cameras or have obstacles for working posture evaluation in the workplace. These study results can be a guideline on proper selection of the number of cameras and their locations for a specific segment and its motion of interest to reduce visual segment angle estimation errors. PMID- 22676051 TI - Methylglyoxal inhibits seed germination and root elongation and up-regulates transcription of stress-responsive genes in ABA-dependent pathway in Arabidopsis. AB - Methylglyoxal (MG) is a highly reactive metabolite derived from glycolysis. In this study, we examined the effect of MG on seed germination, root elongation, chlorosis and stress-responsive gene expression in Arabidopsis using an abscisic acid (ABA)-deficient mutant, aba2-2. In the wild type, 0.1 mm MG did not affect germination but delayed root elongation, whereas 1.0 mm MG inhibited germination and root elongation and induced chlorosis. MG increased transcription levels of RD29B and RAB18 in a dose-dependent manner but did not affect RD29A transcription level. In contrast, in the aba2-2 mutant, MG inhibition of seed germination at 1.0 mm and 10.0 mm and a delay of root elongation at 0.1 mm MG were mitigated, although there was no significant difference in chlorosis between the wild type and mutant. Moreover, the aba2-2 mutation impaired MG-induced RD29B and RAB18 gene expression. These observations suggest that MG not only directly inhibits germination and root elongation but also indirectly modulates these processes via endogenous ABA in Arabidopsis. PMID- 22676053 TI - Effect of non-cell Corynebacterium Parvum on differentiation and maturation of bone marrow-derived dendritic cells. AB - Corynebacterium parvum (CP), with their potent anti-tumor activities, has been well documented. Non-cell Corynebacterium Parvum (NCPP) is a neotype of biological preparation, which based on manipulating CP with nanotechnology. The present study was designed to investigate the effect of NCPP/CP on bone marrow derived dendritic cells (BMDCs) in tumor-bearing mice, especially focused on the differentiation and maturation of these BMDCs. BM cells from tumor-bearing mice administrated with NCPP/CP were analyzed by flow cytometry, which exhibit enhanced numbers of DCs and macrophages. In the meanwhile, flow cytometry analysis showed mild but significant difference for CD80 expression on these LPS- treated BMDCs between NCPP/CP administrated mice and the control animals. Furthermore, antigen presenting assay for these LPS-treated BMDCs showed significant difference for cytolytic assay of CD8+T cells against B16 melanoma cells, which indicate that NCPP treatments have enhanced the cytolytic rates of CD8+T cells from 47.9%+/-2.3% to 54.2%+/-2.4%. The data suggest that NCPP/CP treatment can efficiently facilitate the generation of BMDCs in vivo and enhance the maturation of these BMDCs in vitro. PMID- 22676052 TI - Schistosoma haematobium infections among schoolchildren in central Sudan one year after treatment with praziquantel. AB - BACKGROUND: Chemotherapy with praziquantel (PZQ) is the mainstay of schistosomiasis control. However, there are recent concerns about tolerance or resistance to PZQ, so that monitoring its efficacy in different settings is required. METHODS: A longitudinal study was conducted to evaluate the impact of PZQ for the treatment of Schistosoma haematobium infection among schoolchildren at Al Salamania, Central Sudan. Parasitological examinations for S. haematobium were performed in a cohort of schoolchildren (6-15 years of age) before and 1 year after treatment with a single dose of PZQ 40 mg/kg. RESULTS: Out of 562 (309 boys and 253 girls) schoolchildren recruited from three elementary schools, 420 completed one longitudinal dataset that comprised of data from two time points; baseline, and follow-up 1 year after treatment with a single dose of PZQ 40 mg/kg for S. haematobium infection. A single dose of PZQ significantly reduced the prevalence of S. haematobium infection by 83.3% (from 51.4% to 8.6%) and the geometric mean intensity of infection of positive individuals by 17.0% (from 87.7 to 72.8 eggs/10 ml of urine) 1 year after treatment. While there was no significant difference in the reduction of the prevalence of S. haematobium infection between the gender or age groups, there was a significantly higher reduction of intensity of S. haematobium infection among girls in comparison with boys. CONCLUSION: There was a significant reduction of S. haematobium infection 1 year after PZQ treatment in this setting. PMID- 22676054 TI - Supplementation with aqueous leaf extract of Morinda lucida enhances immunorestoration and upregulates the expression of cytokines and immunostimulatory markers. AB - Morinda lucida Benth (Rubiaceae) is a versatile plant used in traditional medicine of many countries for the treatment of a variety of ailments and the claims of efficacy are particularly remarkable in the treatment of infections and immuno-inflammatory disorders. In this study, we investigated the immunostimulatory and immunorestorative properties of the aqueous leaf extract of Morinda lucida (AML) in cultures of murine splenic lymphocytes and in cyclophosphamide-induced immunosupression models, respectively. Administration of AML (100 and 250 mg/kg; per os) in alternate days significantly (P < 0.05) increased specific total IgG, IgG1, and IgG2a responses to ovalbumin by as much as 2-10 fold when compared to untreated controls. In cyclophophamide treated mice, the rate of wound healing, leukopoiesis , and body weight recovery were all enhanced by oral supplementation with AML (100 and 250 mg/kg) in a dose-dependent manner. In vitro cultures of BALB/C splenocytes treated with AML (12.5 and 50 MUg/ml) for 24 h resulted in 5-10 fold increase in IFNgamma and IL-4 measured by cytokine capture ELISA. Surface expression of immunostimulatory markers, CD69 and CD25, measured flow cytometrically by FACS analyis, were also significantly (P < 0.05) upregulated on splenic T and B cells by as much as 8-20 fold. Taken together, the results of these studies show the potent immunostimulatory and immunorestorative properties of the aqueous leaf extract of Morinda lucida, which may explain some of the beneficial effects of the plant in the treatment of infections and immuno-inflammatory disorders. PMID- 22676055 TI - IQ as a moderator of outcome in severity of children's mental health status after treatment in outpatient clinics. AB - BACKGROUND: Psychotherapy is an effective treatment for mental health disorders, but even with the most efficacious treatment, many patients do not experience improvement. Moderator analysis can identify the conditions under which treatment is effective or whether there are factors that can attenuate the effects of treatment. METHODS: In this study, linear mixed model analysis was used to examine whether the Full Scale IQ (FSIQ), Performance IQ (PIQ) and Verbal IQ (VIQ) on the Wechsler Intelligence Scale for Children - Third Edition, moderated outcomes in general functioning and symptom load. A total of 132 patients treated at three outpatient child and adolescent mental health services (CAMHS) were assessed at three different time points. The Children's Global Assessment Scale (CGAS) and the Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA) were used to measure the severity of impairments in general functioning and symptom load. IQ was assessed at the start of treatment. RESULTS: Moderator analysis revealed that the FSIQ * time interaction predicted changes in CGAS scores (p < .01), and that the PIQ * time interaction predicted changes in HoNOSCA scores (p < .05). The slopes and intercepts in HoNOSCA scores covaried negatively and significantly (p < .05). The same pattern was not detected for the CGAS scores (p = .08). CONCLUSIONS: FISQ and PIQ moderated change in general functioning and symptom load, respectively. This implies that patients with higher IQ scores had a steeper improvement slope than those with lower scores. The patients with the highest initial symptom loads showed the greatest improvement, this pattern was not found in the improvement of general functioning. PMID- 22676057 TI - Circumcision and penile human papillomavirus prevalence in human immunodeficiency virus-infected men: heterosexual and men who have sex with men. AB - Male circumcision is associated with a lower risk of penile human papillomavirus (HPV) infection in human immunodeficiency virus (HIV) uninfected men. Few studies have evaluated the role of male circumcision in penile HPV infection in HIV infected men. The aim of this cross-sectional study was to examine the association between male circumcision and the prevalence of penile HPV infection among HIV-infected men-both men who have sex with men (MSM) and heterosexual men. Samples from 706 consecutive men included in the CARH-MEN cohort (overall 24% circumcised: 26% of MSM, 18% of heterosexual men) were examined by Multiplex-PCR. In the overall group (all HIV-infected men included), the prevalence of any penile HPV infection was 22% in circumcised men and 27% in uncircumcised men (OR = 1.0, 95% CI 0.6-1.6, adjusted analysis). In the circumcised group the overall prevalence of HPV infection was 22% in MSM and 24% in the heterosexual men, whereas in the uncircumcised group the prevalence was 26% and 28%, respectively. The prevalence of high-risk HPV types tended to be lower in the circumcised MSM (14% vs 21%, OR = 0.6, 95% CI 0.3-1.1, p 0.088), but it was similar in the heterosexual men (18% in circumcised vs 20% in uncircumcised). These results suggest that male circumcision may be associated with a lower prevalence of oncogenic high-risk penile HPV infection in HIV-infected MSM. PMID- 22676056 TI - A neurochemical map of the developing amphioxus nervous system. AB - BACKGROUND: Amphioxus, representing the most basal group of living chordates, is the best available proxy for the last invertebrate ancestor of the chordates. Although the central nervous system (CNS) of amphioxus comprises only about 20,000 neurons (as compared to billions in vertebrates), the developmental genetics and neuroanatomy of amphioxus are strikingly vertebrate-like. In the present study, we mapped the distribution of amphioxus CNS cells producing distinctive neurochemicals. To this end, we cloned genes encoding biosynthetic enzymes and/or transporters of the most common neurotransmitters and assayed their developmental expression in the embryo and early larva. RESULTS: By single and double in situ hybridization experiments, we identified glutamatergic, GABAergic/glycinergic, serotonergic and cholinergic neurons in developing amphioxus. In addition to characterizing the distribution of excitatory and inhibitory neurons in the developing amphioxus CNS, we observed that cholinergic and GABAergic/glycinergic neurons are segmentally arranged in the hindbrain, whereas serotonergic, glutamatergic and dopaminergic neurons are restricted to specific regions of the cerebral vesicle and the hindbrain. We were further able to identify discrete groups of GABAergic and glutamatergic interneurons and cholinergic motoneurons at the level of the primary motor center (PMC), the major integrative center of sensory and motor stimuli of the amphioxus nerve cord. CONCLUSIONS: In this study, we assessed neuronal differentiation in the developing amphioxus nervous system and compiled the first neurochemical map of the amphioxus CNS. This map is a first step towards a full characterization of the neurotransmitter signature of previously described nerve cell types in the amphioxus CNS, such as motoneurons and interneurons. PMID- 22676058 TI - Evolution of antibiotic resistance, catabolic pathways and niche colonization. PMID- 22676060 TI - The C-terminal rod 2 fragment of filamin A forms a compact structure that can be extended. AB - Filamins are large proteins that cross-link actin filaments and connect to other cellular components. The C-terminal rod 2 region of FLNa (filamin A) mediates dimerization and interacts with several transmembrane receptors and intracellular signalling adaptors. SAXS (small-angle X-ray scattering) experiments were used to make a model of a six immunoglobulin-like domain fragment of the FLNa rod 2 (domains 16-21). This fragment had a surprising three-branched structural arrangement, where each branch was made of a tightly packed two-domain pair. Peptides derived from transmembrane receptors and intracellular signalling proteins induced a more open structure of the six domain fragment. Mutagenesis studies suggested that these changes are caused by peptides binding to the CD faces on domains 19 and 21 which displace the preceding domain A-strands (18 and 20 respectively), thus opening the individual domain pairs. A single particle cryo-EM map of a nine domain rod 2 fragment (domains 16-24), showed a relatively compact dimeric particle and confirmed the three-branched arrangement as well as the peptide-induced conformation changes. These findings reveal features of filamin structure that are important for its interactions and mechanical properties. PMID- 22676061 TI - Entrapment of metal nanoparticles in polymer stomatocytes. AB - Polymersomes assembled from amphiphilic block copolymers containing a glassy hydrophobic segment can be further re-engineered to perform a controlled shape transformation from a thermodynamically stable spherical morphology to a kinetically trapped stomatocyte structure. The stable bowl-shape stomatocyte morphology is ideal for the specific physical entrapment of nanoparticles for potential use in heterogeneous catalysis and drug delivery. Herein we report two approaches to obtain a selective and controlled entrapment of platinum nanoparticles (PtNP) of different sizes and shapes inside the stomatocyte structure. In the first approach, the stomach of the stomatocytes is used to template the growth of the PtNP by controlling and confining the nucleation points inside the cavity. In the second method, preformed nanoparticles are engulfed during the stomatocyte formation process. Synergistically, the reverse effect is observed, that is, differently shaped nanoparticles were shown to exhibit a templating effect on the stomach formation of the stomatocytes. PMID- 22676062 TI - Reduced expression of antimicrobial PLUNC proteins in nasal polyp tissues of patients with chronic rhinosinusitis. AB - BACKGROUND: Chronic rhinosinusitis (CRS) is a disease characterized by inflammation of the nasal mucosa and paranasal sinuses. This inflammation may result in part from decreased epithelial barrier and innate immune responses, leading to frequent bacterial and fungal colonization. The objectives of this study were to investigate the expression of innate immune proteins of the palate lung and nasal epithelium clone (PLUNC) family in patients with CRS. METHODS: Nasal tissue samples were collected from control subjects and CRS patients with and without nasal polyps. Expression of the members of the PLUNC family was analyzed by real-time PCR. Expression of SPLUNC1 and LPLUNC2 proteins was analyzed by ELISA, immunoblot, and immunohistochemical analysis. RESULTS: Levels of mRNA for most of the members of the PLUNC family were profoundly reduced in nasal polyps (NPs) compared to uncinate tissue from control subjects or patients with CRS. LPLUNC2 and SPLUNC1 proteins were decreased in NPs of patients with CRS compared to uncinate tissue from control subjects. Immunohistochemical data revealed that within submucosal glands of sinonasal tissues, SPLUNC1 and LPLUNC2 were differentially expressed, in serous and mucous cells, respectively. The decrease in the expression of these molecules is probably explained by a decrease in the number of glands in NPs as revealed by correlations with levels of the glandular marker lactoferrin. CONCLUSIONS: Decreased SPLUNC1 and LPLUNC2 in NPs reflect a profound decrease in the number of submucosal glands. Decreased glands may lead to a localized defect in the production and release of glandular innate defense molecules. PMID- 22676063 TI - The role of basophil activation test in special populations with mastocytosis and reactions to hymenoptera sting. AB - BACKGROUND: Systemic mastocytosis (SM) may be associated with hymenoptera allergy. In such cases, immunotherapy is a life-saving treatment, but a circumstantiated diagnosis is needed for its prescription. Patients with SM and previous reactions to stings, but with negative tests represent a diagnostic dilemma. The basophil activation test (BAT) may be helpful in refining the diagnosis. OBJECTIVE: We assessed the usefulness of BAT in subpopulations of mastocytosis patients, including those with negative tests for insect allergy. METHODS: Within a population of patients with mastocytosis and previous stings, we studied by BAT and augmented intradermal test (IDT) (10 ug/ml) two groups: (1) with reactions to stings and negative tests; (2) without reactions and negative tests. Basophil activation test was performed with different venoms, assessing at flow cytometry basophils' activation. RESULTS: Sixty-three patients had mastocytosis and 52 had reactions to previous hymenoptera stings. Of them, seven proved negative to diagnostic tests. In six of seven of those patients, BAT was negative with all venoms, and in one, basophils resulted activated also with the negative control. In six patients without previous reactions and negative tests, BAT was totally negative in five of six patients and weakly positive to Hornet in one. Finally, the IDT at 10 ug/ml venom produced nonspecific positive results in most cases. CONCLUSION: In patients with mastocytosis, the negative results of standard tests are reliable, because BAT and IDT at higher concentration do not add useful information. PMID- 22676064 TI - Can component-resolved diagnosis overturn the current knowledge on vespid allergy? PMID- 22676065 TI - Effects of PEMF and glucocorticoids on proliferation and differentiation of osteoblasts. AB - Pulsed electromagnetic fields (PEMF) can promote bone healing, while use of dexamethasone induces bone loss and osteoporosis. There is no report available on the combined effects of PEMF and dexamethasone on the activity of osteoblasts. Here, we investigated the effects of PEMF and dexamethasone on the proliferation and differentiation of MC3T3-E1 osteoblasts. Our results showed that PEMF and dexamethasone respectively increased and decreased the proliferation of MC3T3-E1 osteoblasts, meanwhile PEMF eliminated the effect of dexamethasone on MC3T3-E1 osteoblasts. Moreover, we also found that dexamethasone combined with PEMF upregulated the mRNA expression of IGF-1 at the early stage after the stimulation of PEMF and improved the decrease of COX-2 mRNA expression induced by dexamethasone at the late stage after the stimulation of PEMF. PEMF may be beneficial to improve dexamethasone-induced bone loss and osteoporosis. PMID- 22676066 TI - HLA-C matching status does not affect rituximab-mediated antibody-dependent cellular cytotoxicity by allogeneic natural killer Cells. AB - Risk of leukemia relapse after T cell-depleted hematopoietic stem cell transplantation is lower in the "HLA-C mismatched" recipient-donor combinations. This might be attributable to increased natural killing by allogeneic NK cells carrying a KIR that does not bind to HLA-C on target cells (HLA-C-uncoupled KIR). Considering a new strategy of allogeneic NK cell transfer with rituximab to treat B-cell lymphomas, however, it is unknown whether the HLA-C matching status also affects rituximab-mediated antibody-dependent cellular cytotoxicity (ADCC). To address this issue, we investigated the levels of ADCC by purified NK cells carrying an HLA-C-uncoupled KIR, where the NK cell donors had either matched or mismatched HLA-C combination with target cells. Purified NK cells carrying an HLA C-uncoupled KIR consistently showed enhanced ADCC against target cells when NK cell donors had an HLA-C-mismatch. When NK cell donors did not have an HLA-C mismatch, it was inconsistent whether HLA-C-uncoupled KIR caused ADCC enhancement. When the levels of ADCC by whole NK cells were compared, there were substantial differences among the donors regardless of the HLA-C matching status. Subjects with HLA-C mismatch may not have an advantage when cytoimmunotherapy using allogeneic NK cells is considered in combination with rituximab. PMID- 22676067 TI - Evaluation of extended release brimonidine intravitreal device in normotensive rabbit eyes. AB - PURPOSE: To evaluate the safety profile of a brimonidine extended release intravitreal implant, in normotensive rabbit eyes. METHODS: Devices were made from hollow poly-l-lactic acid (PLA) tubes and contained hundred micrograms of brimonidine pamoate. Device was injected intravitreally in one eye of 12 New Zealand pigmented rabbits, whereas other eye was injected with a sham implant in masked fashion. Ocular examination was conducted at baseline and months 1, 3 and 6 including dilated fundus examination and electro-retinogram (ERG). Four rabbits were sacrificed at each time-point for retinal histology. ERG data were compared between groups and time-points using anova. RESULTS: No complications were reported from either eye of any rabbits over a 6-month period. Photopic A wave was reduced in the control eye at 1 month compared with baseline (p < 0.01). There was no significant difference in other ERG parameters between the groups at different time-points. Gross retinal histology was normal at all time-points. CONCLUSION: Extended release intravitreal brimonidine device was found to be safe and in normotensive rabbit eyes. PMID- 22676068 TI - Genetic transformation of Neisseria gonorrhoeae shows a strand preference. AB - Natural transformation is the main means of horizontal genetic exchange in the obligate human pathogen Neisseria gonorrhoeae. Neisseria spp. have been shown to preferentially take up and transform their own DNA by recognizing a non palindromic 10 or 12 nucleotide DNA uptake sequence (DUS10 or DUS12). We investigated the ability of the DUS12 to enhance single-stranded DNA (ssDNA) transformation. Given the non-palindromic nature of the DUS12, we tested whether both strands of the DUS equally enhance transformation. Recombinant single stranded M13 phage harboring transforming DNA with the Watson DUS12, the Crick DUS12, or no DUS (DUS0) were constructed and circular ssDNA was purified. Southern blots of the purified DNA probed with strand-specific oligonucleotide probes showed > 10,000 : 1 ratio of ssDNA to contaminating dsDNA. The Crick strand of the DUS12 enhanced ssDNA transformation 180- to 470-fold over DUS0 ssDNA, whereas the Watson strand of the DUS only modestly enhanced ssDNA transformation in two strains of N. gonorrhoeae. These data confirm that ssDNA efficiently transforms N. gonorrhoeae, but that there is a strand preference and that part of this strand preference is a greater efficiency of the Crick strand of the DUS12 in enhancing transformation. PMID- 22676069 TI - An exploratory randomised controlled trial of a premises-level intervention to reduce alcohol-related harm including violence in the United Kingdom. AB - BACKGROUND: To assess the feasibility of a randomised controlled trial of a licensed premises intervention to reduce severe intoxication and disorder; to establish effect sizes and identify appropriate approaches to the development and maintenance of a rigorous research design and intervention implementation. METHODS: An exploratory two-armed parallel randomised controlled trial with a nested process evaluation. An audit of risk factors and a tailored action plan for high risk premises, with three month follow up audit and feedback. Thirty-two premises that had experienced at least one assault in the year prior to the intervention were recruited, match paired and randomly allocated to control or intervention group. Police violence data and data from a street survey of study premises' customers, including measures of breath alcohol concentration and surveyor rated customer intoxication, were used to assess effect sizes for a future definitive trial. A nested process evaluation explored implementation barriers and the fidelity of the intervention with key stakeholders and senior staff in intervention premises using semi-structured interviews. RESULTS: The process evaluation indicated implementation barriers and low fidelity, with a reluctance to implement the intervention and to submit to a formal risk audit. Power calculations suggest the intervention effect on violence and subjective intoxication would be raised to significance with a study size of 517 premises. CONCLUSIONS: It is methodologically feasible to conduct randomised controlled trials where licensed premises are the unit of allocation. However, lack of enthusiasm in senior premises staff indicates the need for intervention enforcement, rather than voluntary agreements, and on-going strategies to promote sustainability. TRIAL REGISTRATION: UKCRN 7090; ISRCTN: 80875696. PMID- 22676070 TI - An open-label, multicenter evaluation of the long-term safety and efficacy of risperidone in adolescents with schizophrenia. AB - BACKGROUND: Data on the long-term efficacy, safety, and tolerability of risperidone in adolescents with schizophrenia are limited. The objective of this study was to evaluate the efficacy and safety of maintenance risperidone treatment in adolescents with schizophrenia. METHODS: This open-label study of adolescents aged 13 to 17 years with schizophrenia was a single extension study of two short-term double-blind risperidone studies and also enrolled subjects directly in open-label risperidone treatment. The risperidone dose was flexible and ranged from 2 to 6 mg/day. Most subjects enrolled for 6 months; a subset enrolled for 12 months. Assessment tools included the Positive and Negative Syndrome Scale total and factor scores, Clinical Global Impressions, Children's Global Assessment Scale, adverse event (AE) monitoring, vital signs, laboratory testing, and extrapyramidal symptom rating scales. RESULTS: A total of 390 subjects were enrolled; 48 subjects had received placebo in a previous double blind study; 292 subjects had received risperidone as part of their participation in one of two previous controlled studies; and 50 subjects were enrolled directly for this study. A total of 279 subjects enrolled for 6 months of treatment, and 111 subjects enrolled for 12 months of treatment. Overall, 264 (67.7%) subjects completed this study: 209 of the 279 subjects (75%) in the 6-month group and 55 of the 111 subjects (50%) in the 12-month group. The median mode dose was 3.8 mg/day. At 6 months, all three groups experienced improvement from open-label baseline in symptoms of schizophrenia as well as general assessments of global functioning. Improvements were generally maintained for the duration of treatment. The most common AEs (>=10% of subjects) were somnolence, headache, weight increase, hypertonia, insomnia, tremor, and psychosis. Potentially prolactin-related AEs (PPAEs) were reported by 36 (9%) subjects. The AE profile in this study was qualitatively similar to those of other studies in adult subjects with schizophrenia and in other psychiatric studies of risperidone in pediatric populations. CONCLUSIONS: Risperidone maintenance treatment in adolescents over 6 to 12 months was well tolerated, consistent with related studies in this clinical population, and associated with continued efficacy. CLINICAL TRIALS: ClinicalTrials.gov registration number: NCT00246285 http://clinicaltrials.gov/ct2/show/NCT00246285?term=NCT00246285&rank=1. PMID- 22676071 TI - Impact of abutment material and dis-/re-connection on soft and hard tissue changes at implants with platform-switching. AB - OBJECTIVES: To assess the impact of abutment material and dis-/re-connection on soft and hard tissue changes at implants with platform-switching. MATERIAL & METHODS: Titanium implants (n = 12), placed epicrestally in the upper jaws of three dogs, were connected with titanium (Ti) and zirconium dioxide (ZrO(2) ) abutments (horizontal mismatch of 0.4 mm) and randomly allocated in a split-mouth design either to repeated (2x) dis-/re-connection at 4 and 6 weeks (test), respectively, or left undisturbed (control). At 8 weeks, histomorphometrical measurements were made between the mucosal margin (PM), implant shoulder (IS) and the apical extension of the long junctional epithelium (aJE),-the most coronal level of bone in contact with the implant (CBI). RESULTS: Repeated abutment manipulation was associated with increased mean PM-aJE and IS-CBI values at both Ti (1.82 +/- 0.37-1.99 +/- 0.40 mm and 0.72 +/- 0.18-1.12 +/- 0.60 mm) and ZrO(2) (1.90 +/- 0.28-2.67 +/- 0.67 mm and 0.22 +/- 0.10-2.15 +/- 0.77 mm) abutments at 8 weeks. These vertical dimensions were comparable at both vestibular and oral aspects. Between group comparisons, however, failed to reveal a significant difference between test and control sites. CONCLUSIONS: Repeated manipulation may be associated with dimensional changes of peri-implant soft and hard tissues formed at both non-matching Ti and ZrO(2) abutments. PMID- 22676072 TI - Widespread yet heterogeneous genomic divergence. AB - Genetic differentiation during adaptive divergence and speciation is heterogeneous among genomic regions. Some regions can be highly differentiated between populations, for example, because they harbour genes under divergent selection or those causing reproductive isolation and thus are resistant to gene flow. Other regions might be homogenized by gene flow and thus weakly differentiated. Debates persist about the number of differentiated regions expected under divergence with gene flow, and their causes, size, and genomic distribution. In this issue of Molecular Ecology, a study of freshwater stickleback used next-generation sequencing to shed novel insight into these issues (Roesti et al. 2012). Many genomic regions distributed across the genome were strongly differentiated, indicating divergence with gene flow can involve a greater number of loci than often thought. Nonetheless, differentiation of some regions, such as those near the centre of chromosomes where recombination is reduced, was strongly accentuated over others. Thus, divergence was widespread yet highly heterogeneous across the genome. Moreover, different population pairs varied in patterns of differentiation, illustrating how genomic divergence builds up across stages of the speciation process. The study demonstrates how variation in different evolutionary processes, such as selection and recombination rate, can combine to result in similar genomic patterns. Future work could focus on teasing apart the contributions of different processes for causing differentiation, a task facilitated by experimental manipulations. PMID- 22676073 TI - Bad coat, ripped genes: cryptic selection on coat colour varies with ontogeny in Soay sheep. AB - A fundamental goal for evolutionary biologists is to connect the processes of natural selection and genetic drift with the maintenance of genetic variation in the wild. There are now scores of examples in which mapping phenotypes to genotypes has identified the molecular basis of traits in natural populations, but documenting the fitness consequences of these genes has proven more elusive. A long-term study of several thousand unmanaged sheep on the remote Scottish island of Hirta in the St. Kilda archipelago provides a unique opportunity to make these connections between genotype, phenotype and fitness. Since 1985, there has been a steady decline in the frequency of sheep with a rare uniform ('self'-) pigmentation pattern as opposed to the more common wild-type pattern of dark upper body and pale belly. In this issue of Molecular Ecology, Gratten et al. (2012) link variation at the agouti signalling protein (ASIP) gene with 25 years of pedigree information and individual fitness data to investigate the contributions of natural selection and genetic drift to this decline. Consistent with the decrease in frequency of self-type sheep, Gratten et al. demonstrate that recessive genetic variants at ASIP are associated with reduced lifetime fitness. But surprisingly, these variants show the opposite trend to the self type phenotype by increasing throughout the study period. This paradoxical result occurs because heterozygotes that harbour the majority of self-type alleles have increased in frequency. This pattern would not have been detectable if only phenotype had been monitored because the pigmentation pattern of heterozygotes is indistinguishable from that of wild-type homozygotes. The study provides an excellent example of the importance of measuring selection at both the phenotypic and genetic level, and demonstrates how long-term pedigrees can be used to link alleles to phenotypes and ultimately to fitness. PMID- 22676074 TI - Defining the landscape of adaptive genetic diversity. AB - Whether they are used to describe fitness, genome architecture or the spatial distribution of environmental variables, the concept of a landscape has figured prominently in our collective reasoning. The tradition of landscapes in evolutionary biology is one of fitness mapped onto axes defined by phenotypes or molecular sequence states. The characteristics of these landscapes depend on natural selection, which is structured across both genomic and environmental landscapes, and thus, the bridge among differing uses of the landscape concept (i.e. metaphorically or literally) is that of an adaptive phenotype and its distribution across geographical landscapes in relation to selective pressures. One of the ultimate goals of evolutionary biology should thus be to construct fitness landscapes in geographical space. Natural plant populations are ideal systems with which to explore the feasibility of attaining this goal, because much is known about the quantitative genetic architecture of complex traits for many different plant species. What is less known are the molecular components of this architecture. In this issue of Molecular Ecology, Parchman et al. (2012) pioneer one of the first truly genome-wide association studies in a tree that moves us closer to this form of mechanistic understanding for an adaptive phenotype in natural populations of lodgepole pine (Pinus contorta Dougl. ex Loud.). PMID- 22676076 TI - Advances in improvement of quality and resistance in a multipurpose crop: sea buckthorn. AB - Sea buckthorn is a berry crop with multiple uses. The berries are highly appreciated for their unique taste but are also very rich in bioactive compounds with powerful nutritional and medicinal values. In addition, the plants grow well under adverse conditions, and are often used to fight soil erosion. Utilization of sea buckthorn has therefore increased around the world but serious problems have, nevertheless, been encountered due to drought, salinity, diseases and insect pests. This review covers important aspects of sea buckthorn research, such as heritable and environmentally induced variation in biochemical compounds, causes and effects of the devastating dried-shrink disease, susceptibility to insect pests, methods for conventional breeding, and the utilization of DNA markers for taxonomical and population genetic analyses, and for investigating the inheritance of quality and resistance traits. We also present possibilities to implement innovative biotechnological breeding methods, especially metabolite profiling and MAS/GRC-based markers, for fast and efficient development of elite genotypes with specific nutritional- and health-related bioactive compounds and strong resistance to biotic and abiotic stress. PMID- 22676077 TI - Interrelationships between spider fear associations, attentional disengagement and self-reported fear: a preliminary test of a dual-systems model. AB - Recent conceptualisations of anxiety posit that equivocal findings related to the time-course of disengaging from threat-relevant stimuli may be attributable to individual differences in associative and rule-based processing. The current study was designed to test the hypothesis that strength of spider-fear associations would indirectly predict reported spider fear via impaired disengagement. One hundred and thirty-one undergraduate volunteer participants completed the Go/No-go Association Task, a visual search task, and self-report spider fear questionnaires. Stronger spider-fear associations were associated with reduced disengagement accuracy, whereas higher levels of reported spider fear were related to faster engagement with and disengagement from spiders. Bootstrapping multiple mediation analyses demonstrated that stronger-spider fear associations evidenced an indirect relationship with reported spider fear via reduced disengagement accuracy, highlighting the importance of fine-grained analyses of different aspects of cognitive bias. Results are discussed in terms of cognitive models of anxiety. PMID- 22676080 TI - Centralized Access is Here! Featuring. PMID- 22676078 TI - Liver abscesses in adult patients with and without diabetes mellitus: an analysis of the clinical characteristics, features of the causative pathogens, outcomes and predictors of fatality: a report based on a large population, retrospective study in China. AB - In China, there are four types of liver abscesses (LAs) that meet the clinical criteria. Pyogenic liver abscesses (PLAs) and amoebic liver abscesses (ALAs) are two of the most common types of abscesses, followed by fungal liver abscesses (FLAs) and hydatid secondary liver abscesses (HsLAs). Diabetes mellitus (DM) is associated with the development of PLAs. However, there is a lack of population based studies that have evaluated the underlying relationship between LAs (mainly PLAs and FLAs) and DM. We conducted a retrospective study based on a large population to identify the potential differences and factors that affect the mortality of PLA patients in DM and non-DM groups. Our results revealed that the prevalence of DM is 44.3% (158/357) in PLA patients and 35.3% (18/51) in FLA patients. Compared with the non-DM patients, statistically significant differences were found in DM patients according to symptomatology, clinical manifestations, laboratory findings, microbiological characteristics, antimicrobial resistance, clinical treatments and outcomes in relation to mortality. In addition, the status of antibiotic resistance to E. coli and K. pneumoniae, which were isolated from the patient samples, is severe in the area in which the study was conducted. Regarding the treatment of PLAs, our study indicated that broad-spectrum antimicrobial therapy and drug combinations should be recommended and initiated before the pathogens are cultured and identified. In the clinic, therapies that combine percutaneous drainage with antibiotics and surgery with antibiotics are the two most useful strategies for treating an LA. These two combined treatments resulted in satisfactory cure rates. In the DM and non-DM groups, the cure rates for percutaneous drainage with antibiotics were 90.3% and 92.0%, respectively, and the cure rates for surgery with antibiotics were 93.9% and 95.2%, respectively. PMID- 22676079 TI - John wiley & sons, inc. PMID- 22676082 TI - Correction. PMID- 22676081 TI - Biotechnica. PMID- 22676084 TI - Great Lakes dioxin source. PMID- 22676083 TI - Aquatic chemistry: interfacial and interspecies processes. PMID- 22676085 TI - PAH metabolism. PMID- 22676087 TI - Sediment screening. PMID- 22676086 TI - In situ vinyl chloride transformation. PMID- 22676088 TI - Mixed phenol species. PMID- 22676089 TI - Jet fuel in groundwater. PMID- 22676090 TI - Herbicide detection. PMID- 22676091 TI - Screening tests. PMID- 22676092 TI - Tracer effects on microbes. PMID- 22676093 TI - Health effects vs. exposure. PMID- 22676094 TI - Checking mass spectroscopy database reliability. PMID- 22676095 TI - Chlorophenol oxidation. PMID- 22676096 TI - Sampling economies. PMID- 22676097 TI - Sustainable development. PMID- 22676098 TI - Probabilistic paradigm. PMID- 22676099 TI - Stay ahead of the curve. PMID- 22676101 TI - Superfund reforms announced. PMID- 22676100 TI - Bacterial corrosion. PMID- 22676102 TI - Dioxin sources, levels to be revised. PMID- 22676103 TI - New hazardous waste baselines proposed. PMID- 22676104 TI - ORD drafting strategic research plans. PMID- 22676106 TI - Site classification system pilot planned. PMID- 22676105 TI - Regulatory cost-benefit analysis to expand. PMID- 22676107 TI - House bill cuts DOE environmental research, remediation funds. PMID- 22676108 TI - States join to certify technologies. PMID- 22676109 TI - Endangered species protection redefined by NRC report. PMID- 22676110 TI - National ecological center to open. PMID- 22676111 TI - Sustainable development plan due this fall. PMID- 22676112 TI - Contractors selected for NY/NJ sediment cleanup pilot. PMID- 22676113 TI - Subsurface barrier trapped diverse contaminants, let water through. PMID- 22676114 TI - EPA gives go-ahead to VOCs/NOX trading. PMID- 22676115 TI - House cuts climate change research. PMID- 22676116 TI - EPA "nonmission" research targeted by House subcommittee. PMID- 22676117 TI - Global control of persistent organic pollutants advocated. PMID- 22676118 TI - Economic benefits of coastal management praised. PMID- 22676120 TI - The Scientific Breakthrough That Won't Break You. PMID- 22676121 TI - Weighing the health risks of airborne particulates. PMID- 22676122 TI - New elements. A stronger bond. PMID- 22676124 TI - Is there a safe level of exposure to a carcinogen? PMID- 22676123 TI - Is there cause for "environmental optimism"? PMID- 22676125 TI - BOTTOM UNE: The more you read the higher you go. PMID- 22676127 TI - STEP AHEAD with ANALYTICAL CHEMISTRY. PMID- 22676126 TI - Transforming industry. PMID- 22676129 TI - At last! The piece that helps you solve the health and safety puzzle for everyone working with chemicals. PMID- 22676128 TI - Analytical products. PMID- 22676131 TI - Now get all the product. PMID- 22676132 TI - Classified section. PMID- 22676134 TI - Professional consultants services directory. PMID- 22676135 TI - miR-297 modulates multidrug resistance in human colorectal carcinoma by down regulating MRP-2. AB - Colorectal carcinoma is a frequent cause of cancer-related death in men and women. miRNAs (microRNAs) are endogenous small non-coding RNAs that regulate gene expression negatively at the post-transcriptional level. In the present study we investigated the possible role of microRNAs in the development of MDR (multidrug resistance) in colorectal carcinoma cells. We analysed miRNA expression levels between MDR colorectal carcinoma cell line HCT116/L-OHP cells and their parent cell line HCT116 using a miRNA microarray. miR-297 showed lower expression in HCT116/L-OHP cells compared with its parental cells. MRP-2 (MDR-associated protein 2) is an important MDR protein in platinum-drug-resistance cells and is a predicted target of miR-297. Additionally miR-297 was down-regulated in a panel of human colorectal carcinoma tissues and negatively correlated with expression levels of MRP-2. Furthermore, we found that ectopic expression of miR-297 in MDR colorectal carcinoma cells reduced MRP-2 protein level and sensitized these cells to anti-cancer drugs in vitro and in vivo. Taken together, our findings suggest that miR-297 could play a role in the development of MDR in colorectal carcinoma cells, at least in part by modulation of MRP-2. PMID- 22676136 TI - Structure and dynamics of photogenerated triplet radical ion pairs in DNA hairpin conjugates with anthraquinone end caps. AB - A series of DNA hairpins (AqGn) possessing a tethered anthraquinone (Aq) end capping group were synthesized in which the distance between the Aq and a guanine cytosine (G-C) base pair was systematically varied by changing the number (n - 1) of adenine-thymine (A-T) base pairs between them. The photophysics and photochemistry of these hairpins were investigated using nanosecond transient absorption and time-resolved electron paramagnetic resonance (TREPR) spectroscopy. Upon photoexcitation, (1*)Aq undergoes rapid intersystem crossing to yield (3*)Aq, which is capable of oxidizing purine nucleobases resulting in the formation of (3)(Aq(-*)Gn(+*)). All (3)(Aq(-*)Gn(+*)) radical ion pairs exhibit asymmetric TREPR spectra with an electron spin polarization phase pattern of absorption and enhanced emission (A/E) due to their different triplet spin sublevel populations, which are derived from the corresponding non-Boltzmann spin sublevel populations of the (3*)Aq precursor. The TREPR spectra of the (3)(Aq( *)Gn(+*)) radical ion pairs depend strongly on their spin-spin dipolar interaction and weakly on their spin-spin exchange coupling. The anisotropy of (3)(Aq(-*)Gn(+*)) makes it possible to determine that the pi systems of Aq(-*) and G(+*) within the radical ion pair are parallel to one another. Charge recombination of the long-lived (3)(Aq(-*)Gn(+*)) radical ion pair displays an unusual bimodal distance dependence that results from a change in the rate determining step for charge recombination from radical pair intersystem crossing for n < 4 to coherent superexchange for n > 4. PMID- 22676137 TI - Triazole linked picolylimine conjugate of calix[6]arene as a sequential sensor for La3+ followed by F-. AB - A new 1,3,5-tris-triazole linked picolylimine conjugate of calix[6]arene (L) has been shown to be selective toward La(3+) by turn on fluorescence with ~70-fold enhancement and emits blue, with a minimal detection limit of 65 +/- 5 ppb (490 nM). The species of recognition has been modeled computationally to have a monocapped twisted square antiprism with a N(6)O(3) binding core about La(3+). The in situ complex of L with La(3+) recognizes F(-) via fluorescence quenching. The reversible response of sensing La(3+) and F(-) sequentially by L has been demonstrated. PMID- 22676138 TI - EMOST: Report about the application of low-frequency and intensity electromagnetic fields in disaster situation and commando training. AB - Recently, we published our results (Bokkon et al., 2011. Electromagn Biol Med.) regarding the effectiveness of the EMOST (Electro-Magnetic-Own-Signal-Treatment) method for the reduction of phantom limb pain under clinical circumstances. However, EMOST treatments not only significantly reduced phantom pain, but that most of the patients also reported about additional benefits such as improvement of their sleep and mood quality after treatments. Here we report some unusual applications of EMOST method under special situations. That is, we report about our effective EMOST treatments of humans under catastrophic conditions and commando training course. This article points out that it is reasonable to apply biophysical electromagnetic management under unique circumstances. We also report some preliminary experiments on 12 members of our BioLabor regarding the effectiveness of single EMOST treatment on some serum parameters and electrocardiogram. PMID- 22676139 TI - Ultrastructure of hydathode trichomes of hemiparasitic Rhinanthus alectorolophus and Odontites vernus: how important is their role in physiology and evolution of parasitism in Orobanchaceae? AB - The Rhinanthoid clade of the family Orobanchaceae comprises plants displaying a hemiparasitic or holoparasitic strategy of resource acquisition. Some of its species (mainly Rhinanthus spp.) are often used as models for studies of hemiparasite physiology. Although there is a well-developed concept covering their physiological processes, most recent studies have neglected the existence of hydathode trichomes present on leaves of these hemiparasitic plants. As a first step for the proposed integration of these structures in the theory of physiological processes of the hemiparasites, we described the outer micromorphology and ultrastructure of the hydathode trichomes on leaves of hemiparasitic Rhinanthus alectorolophus and Odontites vernus with scanning and transmission electron microscopy (SEM and TEM, respectively). The TEM inspections of both types of trichome revealed typical ultrastructural features: labyrinthine cell wall, high content of cytoplasm in cells with numerous mitochondria and presence of plasmodesmata. All these features indicate high metabolic activity complying with their function as glandular trichomes actively secreting water. The active secretion of water by the hydathode trichomes (evidence for which is summarised here) also presents a possible mechanism explaining results of previous gas exchange measurements detecting high dark respiration and transpiration rates and a tight inter-correlation between them in hemiparasitic Orobanchaceae. In addition, this process is hypothesised to have allowed multiple evolutionary transitions from facultative to obligate hemiparasitism and unique xylem-feeding holoparasitism of Lathraea with a long-lived underground stage featuring a rhizome covered by scales of leaf origin. PMID- 22676140 TI - Assessment of right ventricular mechanics in patients with mitral stenosis by two dimensional deformation imaging. AB - BACKGROUND: It is well known that right ventricular (RV) dysfunction occurs early before clinical systemic congestion in patients with mitral stenosis (MS). Therefore, we aimed to evaluate the role of two-dimensional (2D) strain imaging in the assessment of subclinical RV dysfunction. METHODS: Fifty-nine patients with isolated MS (mild and moderate) and 31 healthy control subjects constituted the study population. RV peak longitudinal strain (RV-LS) and strain rate (RV LSr) measurements were obtained from apical four-chamber view. RESULTS: There were no significant differences in left ventricular ejection fraction (LV-EF) and RV fractional area change between control and MS groups. RV strain (23.5 +/- 7.2 vs. 18.63 +/- 6.3, P = 0.001) and RV strain rate (1.72 +/- 0.54 vs. 1.37 +/- 0.66, P = 0.01) measurements were significantly lower in patients with MS than the control group. However, RV strain and strain rate measurements were comparable between MS subgroups. Correlation analysis revealed that there was poor correlation between RV-LS/LSr and mean-maximum gradients and echoscore but moderate correlation between RV-LS and RV-Sr in systolic pulmonary artery pressure and planimetric mitral valve area. CONCLUSION: We demonstrated that patients with MS had lower RV functions using 2D strain imaging and this is independent from severity of MS. In the detection of subclinical RV dysfunction in patients with MS, 2D strain imaging appears to be useful. (Echocardiography, 2012;00:1-6). PMID- 22676141 TI - The rise and rise of interprofessional competence. PMID- 22676143 TI - Cataract surgeons outperform medical students in Eyesi virtual reality cataract surgery: evidence for construct validity. AB - PURPOSE: To investigate construct validity for modules hydromaneuvers and phaco on the Eyesi surgical simulator. METHODS: Seven cataract surgeons and 17 medical students performed capsulorhexis, hydromaneuvers, phaco, navigation, forceps, cracking and chopping modules in a standardized manner. Three trials were performed on each module (two on phaco) in the above order. Performance parameters as calculated by the simulator for each trial were saved. Video recordings of the second trial of the modules capsulorhexis, hydromaneuvers and phaco were evaluated with the modified Objective Structured Assessment of Surgical Skill (OSATS) and Objective Structured Assessment of Cataract Surgical Skill (OSACSS) tools. RESULTS: Cataract surgeons outperformed medical students with regard to overall score on capsulorhexis (p < 0.001, p = 0.035, p = 0.010 for the tree iterations, respectively), navigation (p = 0.024, p = 0.307, p = 0.007), forceps (p = 0.017, p = 0.03, p = 0.028). Less obvious differences in overall score were found for modules cracking and chopping (p = 0.266, p = 0.022, p = 0.324) and phaco (p = 0.011, p = 0.081 for the two iterations, respectively). No differences in overall score were found on hydromaneuvers (p = 0.588, p = 0.503, p = 0.773), but surgeons received better scores from the evaluations of the modified OSATS (p = 0.001) and OSACSS (capsulorhexis, p = 0.003; hydromaneuvers, p = 0.017; phaco, p = 0.001). CONCLUSIONS: Construct validity was found on several modules previously not investigated (phaco, hydromaneuvers, cracking and chopping, navigation), and our results confirm previously demonstrated construct validity for capsulorhexis and forceps modules. Interestingly, validation of the hydromaneuvers module required OSACSS video evaluation tool. A further development of the scoring system in the simulator for the hydromaneuvers module would be advantageous and make training and evaluation of progress more accessible and immediate. PMID- 22676144 TI - IgE to recombinant allergens Api m 1, Ves v 1, and Ves v 5 distinguish double sensitization from crossreaction in venom allergy. AB - BACKGROUND: Diagnostic tests in patients with Hymenoptera venom allergy are frequently positive to venoms of both honey bee and wasp (Vespula). Component resolved analysis with recombinant species-specific major allergens (rSSMA) may help to distinguish true double sensitization from crossreactivity. METHODS: Included were 121 patients with systemic allergic reactions to Hymenoptera stings, 76 with double positivity of serum-specific IgE (sIgE) to both venoms, 45 with single positivity to bee or wasp venom, and 32 controls without history of systemic reactions to Hymenoptera stings and no sIgE to whole venoms. In venom allergic patients and controls, sIgE to rSSMA Api m 1 of bee venom and to Ves v 1 and Ves v 5 of wasp venom were tested by ImmunoCAP. RESULTS: Only 47% of 76 patients with double positivity to whole venoms reacted also to rSSMA of both species. Specificity of sIgE to the 3 rSSMA was very high, with no sIgE to rSSMA of the other species in single-positive venom-allergic patients and only one control with low sIgE to Ves v 1. All wasp-allergic single-positive patients had sIgE to Ves v 5 and/or Ves v 1, and 78.3% of single-positive bee venom-allergic patients had sIgE to Api m 1. CONCLUSION: Specificity of sIgE to rSSMA of both species is excellent. Sensitivity of sIgE to rSSMA was optimal for wasp venom. Sensitivity of bee venom Api m 1 could be increased by adding rSSMA of other important bee venom allergens. PMID- 22676146 TI - Metabolism, diet and disease Washington, DC, USA. 29-31 May 2012. Abstracts. PMID- 22676145 TI - New reference values must be established for the Alberta Infant Motor Scales for accurate identification of infants at risk for motor developmental delay in Flanders. AB - BACKGROUND: The Alberta Infant Motor Scales (AIMS) is a reliable and valid assessment tool to evaluate the motor performance from birth to independent walking. This study aimed to determine whether the Canadian reference values on the AIMS from 1990-1992 are still useful tor Flemish infants, assessed in 2007 2010. Additionally, the association between motor performance and sleep and play positioning will be determined. METHODS: A total of 270 Flemish infants between 0 and 18 months, recruited by formal day care services, were assessed with the AIMS by four trained physiotherapists. Information about sleep and play positioning was collected by mean of a questionnaire. RESULTS: Flemish infants perform significantly lower on the AIMS compared with the reference values (P < 0.001). Especially, infants from the age groups of 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 and of 15 months showed significantly lower scores. From the information collected by parental questionnaires, the lower motor scores seem to be related to the sleep position, the amount of play time in prone, in supine and in a sitting device. Infants who are exposed often to frequently to prone while awake showed a significant higher motor performance than infants who are exposed less to prone (<6 m: P = 0.002; >6 m: P = 0.013). Infants who are placed often to frequently in a sitting device in the first 6 months of life (P = 0.010) and in supine after 6 months (P = 0.001) performed significantly lower than those who are placed less in it. CONCLUSION: Flemish infants recruited by formal day care services, show significantly lower motor scores than the Canadian norm population. New reference values should be established for the AIMS for accurate identification of infants at risk. Prevention of sudden infant death syndrome by promoting supine sleep position should go together with promotion of tummy time when awake and avoiding to spent too much time in sitting devices when awake. PMID- 22676148 TI - Glacier dynamics and water balance in the Qinghai-Tibet Plateau. PMID- 22676149 TI - Regional differences in cortical electroencephalogram (EEG) slow wave activity and interhemispheric EEG asymmetry in the fur seal. AB - Slow wave sleep (SWS) in the northern fur seal (Callorhinus ursinus) is characterized by a highly expressed interhemispheric electroencephalogram (EEG) asymmetry, called 'unihemispheric' or 'asymmetrical' SWS. The aim of this study was to examine the regional differences in slow wave activity (SWA; power in the range of 1.2-4.0 Hz) within one hemisphere and differences in the degree of interhemispheric EEG asymmetry within this species. Three seals were implanted with 10 EEG electrodes, positioned bilaterally (five in each hemisphere) over the frontal, occipital and parietal cortex. The expression of interhemispheric SWA asymmetry between symmetrical monopolar recordings was estimated based on the asymmetry index [AI = (L-R)/(L+R), where L and R are the power in the left and right hemispheres, respectively]. Our findings indicate an anterior-posterior gradient in SWA during asymmetrical SWS in fur seals, which is opposite to that described for other mammals, including humans, with a larger SWA recorded in the parietal and occipital cortex. Interhemispheric EEG asymmetry in fur seals was recorded across the entire dorsal cerebral cortex, including sensory (visual and somatosensory), motor and associative (parietal or suprasylvian) cortical areas. The expression of asymmetry was greatest in occipital-lateral and parietal derivations and smallest in frontal-medial derivations. Regardless of regional differences in SWA, the majority (90%) of SWS episodes with interhemispheric EEG asymmetry meet the criteria for 'unihemispheric SWS' (one hemisphere is asleep while the other is awake). The remaining episodes can be described as episodes of bilateral SWS with a local activation in one cerebral hemisphere. PMID- 22676147 TI - A systematic review of interventions to increase breast and cervical cancer screening uptake among Asian women. AB - BACKGROUND: The Asian population is one of the fastest growing ethnic minority groups in western countries. However, cancer screening uptake is consistently lower in this group than in the native-born populations. As a first step towards developing an effective cancer screening intervention program targeting Asian women, we conducted a comprehensive systematic review, without geographic, language or date limitations, to update current knowledge on the effectiveness of existing intervention strategies to enhance breast and cervical screening uptake in Asian women. METHODS: This study systematically reviewed studies published as of January 2010 to synthesize knowledge about effectiveness of cancer screening interventions targeting Asian women. Fifteen multidisciplinary peer-reviewed and grey literature databases were searched to identify relevant studies. RESULTS: The results of our systematic review were reported in accordance with the PRISMA Statement. Of 37 selected intervention studies, only 18 studies included valid outcome measures (i.e. self-reported or recorded receipt of mammograms or Pap smear). 11 of the 18 intervention studies with valid outcome measures used multiple intervention strategies to target individuals in a specific Asian ethnic group. This observed pattern of intervention design supports the hypothesis that employing a combination of multiple strategies is more likely to be successful than single interventions. The effectiveness of community-based or workplace based group education programs increases when additional supports, such as assistance in scheduling/attending screening and mobile screening services are provided. Combining cultural awareness training for health care professionals with outreach workers who can help healthcare professionals overcome language and cultural barriers is likely to improve cancer screening uptake. Media campaigns and mailed culturally sensitive print materials alone may be ineffective in increasing screening uptake. Intervention effectiveness appears to vary with ethnic population, methods of program delivery, and study setting. CONCLUSIONS: Despite some limitations, our review has demonstrated that the effectiveness of existing interventions to promote breast and cervical cancer screening uptake in Asian women may hinge on a variety of factors, such as type of intervention and study population characteristics. While some studies demonstrated the effectiveness of certain intervention programs, the cost effectiveness and long term sustainability of these programs remain questionable. When adopting an intervention program, it is important to consider the impacts of social-and cultural factors specific to the Asian population on cancer screening uptake. Future research is needed to develop new interventions and tools, and adopt vigorous study design and evaluation methodologies to increase cancer screening among Asian women to promote population health and health equity. PMID- 22676156 TI - Erratum, Erratum, Erratum, Erratum. PMID- 22676150 TI - Evaluating the competing risks of HIV acquisition and maternal mortality in Africa: a decision analysis. AB - OBJECTIVE: To model the risk of HIV acquisition and maternal mortality for women in four African countries in the light of previous data on risk of HIV acquisition and hormonal contraceptive use. DESIGN: Decision analysis. SETTING: Chad, Kenya, South Africa and Uganda. POPULATION: Women of reproductive age, at risk of HIV, who do not desire pregnancy. METHODS: A decision analysis model was built to compare the consequences of removing progestin injectables from use, assuming an increased risk of HIV acquisition. Three scenarios were considered in four African countries: replacement of progestin injectables with no method, with combined oral contraceptives (COC) or with an intrauterine device (IUD). Health outcomes measured include: life-years, maternal mortality, HIV acquisition and unsafe abortion. Sensitivity analysis, including Monte Carlo simulation, was performed around all variables. MAIN OUTCOME MEASURES: HIV acquisition, maternal mortality and life-years. RESULTS: If progestin injectables are removed from use, without a minimum of 70-100% of women switching to an IUD or COCs, up to nine additional maternal deaths will occur for every case of HIV averted. Sensitivity analysis demonstrated that this finding persisted across a broad range of variables. CONCLUSIONS: Contraception is critical to preserving life for women in Africa. In the absence of clear evidence regarding hormonal contraception and HIV acquisition, policy decisions must not overlook the very real risk of maternal mortality. PMID- 22676157 TI - siRNA against the G gene of human metapneumovirus. AB - BACKGROUND: Human metapneumovirus (hMPV) is a significant viral respiratory pathogen of infants and children, the elderly and immunocompromised individuals. Disease associated with hMPV infection resembles that of human respiratory syncytial virus (RSV) and includes bronchiolitis and pneumonia. The glycosylated G attachment protein of hMPV is required for viral entry in vivo and has also been identified as an inhibitor of innate immune responses. FINDINGS: We designed and validated two siRNA molecules against the G gene using A549 cells and demonstrated consistent 88-92% knock-down for one siRNA molecule, which was used in subsequent experiments. Significant reduction of G mRNA in A549 cells infected with hMPV did not result in a reduction in viral growth, nor did it significantly increase the production of type I interferon (alpha/beta) in response to infection. However, there was a moderate increase in IFN-beta mRNA expression in response to infection in siG-transfected cells compared to untransfected and si mismatch-transfected cells. Expression of G by recombinant adenovirus did not affect type I IFN expression. CONCLUSION: G has been previously described as a type I interferon antagonist, although our findings suggest it may not be a significant antagonist. PMID- 22676158 TI - Abstracts of OsteoRheumatology 2011, the International Congress on Bone Involvement in Arthritis. Santa Margherita Ligure, Italy. October 13-41, 2011. PMID- 22676159 TI - Replacing -CH2CH2- with -CONH- does not significantly change rates of charge transport through Ag(TS)-SAM//Ga2O3/EGaIn junctions. AB - This paper describes physical-organic studies of charge transport by tunneling through self-assembled monolayers (SAMs), based on systematic variations of the structure of the molecules constituting the SAM. Replacing a -CH(2)CH(2)- group with a -CONH- group changes the dipole moment and polarizability of a portion of the molecule and has, in principle, the potential to change the rate of charge transport through the SAM. In practice, this substitution produces no significant change in the rate of charge transport across junctions of the structure Ag(TS) S(CH(2))(m)X(CH(2))(n)H//Ga(2)O(3)/EGaIn (TS = template stripped, X = -CH(2)CH(2) or -CONH-, and EGaIn = eutectic alloy of gallium and indium). Incorporation of the amide group does, however, increase the yields of working (non-shorting) junctions (when compared to n-alkanethiolates of the same length). These results suggest that synthetic schemes that combine a thiol group on one end of a molecule with a group, R, to be tested, on the other (e.g., HS~CONH~R) using an amide-based coupling provide practical routes to molecules useful in studies of molecular electronics. PMID- 22676160 TI - Three-dimensional echocardiographic features of unicuspid aortic valve stenosis correlate with surgical findings. AB - A unicuspid aortic valve (UAV) is a rare congenital defect that may manifest clinically as severe aortic stenosis or regurgitation in the third to fifth decade of life. This report describes two cases of UAV stenosis in adult patients diagnosed by transesophageal echocardiography (TEE). The utility of three dimensional TEE in confirming valve morphology and its relevance to transcatheter valve replacement are discussed. PMID- 22676161 TI - Effect of urine pH changed by dietary intervention on uric acid clearance mechanism of pH-dependent excretion of urinary uric acid. AB - BACKGROUND: The finding reported in a previous paper - alkalization of urine facilitates uric acid excretion - is contradictory to what one might expect to occur: because food materials for the alkalization of urine contain fewer purine bodies than those for acidification, less uric acid in alkaline urine should have been excreted than in acid urine. To make clear what component of uric acid excretion mechanisms is responsible for this unexpected finding, we simultaneously collected data for the concentration of both creatinine and uric acid in serum as well as in urine, in order to calculate both uric acid and creatinine clearances. METHODS: Within the framework of the Japanese government's health promotion program, we made recipes which consisted of protein-rich and less vegetable-fruit food materials for H + -load (acidic diet) and others composed of less protein and more vegetable-fruit rich food materials (alkaline diet). This is a crossover study within some limitations. Healthy female students, who had no medical problems at the regular physical examination provided by the university, were enrolled in this consecutive 5-day study for each test. From whole-day collected urine, total volume, pH, organic acid, creatinine, uric acid, titratable acid and all cations (Na+,K+,Ca2+,Mg2+,NH4+) and anions (Cl-,SO42-,PO4-) necessary for the estimation of acid-base balance were measured. In the early morning before breakfast of the 1st, 3rd and 5th experimental day, we sampled 5 mL of blood to estimate the creatinine and uric acid concentration in serum. RESULTS AND DISCUSSION: Urine pH reached a steady state 3 days after switching from ordinary daily diets to specified regimens. The amount of acid generated ([SO42-] + organic acid - gut alkali)was linearly related with the excretion of acid (titratable acid + [NH4+] - [HCO3-]), indicating that H + in urine is generated by the metabolic degradation of food materials. Uric acid and excreted urine pH retained a linear relationship, as reported previously. Among the five factors which are associated with calculating clearances for both uric acid and creatinine, we identified a conspicuous difference between acidic and alkaline diets in the uric acid concentration in serum as well as in urine; uric acid in the serum was higher in the acidic group than in the alkaline group, while uric acid in the urine in the acidic group was lower than that in the alkaline group. These changes of uric acid in acidic urine and in serum were reflected in the reduction of its clearance. From these observations, it is considered that uric acid may be reabsorbed more actively in acidic urine than in alkaline urine. CONCLUSION: We conclude that alkalization of urine by eating nutritionally well-designed alkaline -prone food is effective for removing uric acid from the body. PMID- 22676162 TI - Enantioselective intramolecular formal [2 + 4] annulation of acrylates and alpha,beta-unsaturated imines catalyzed by amino acid derived phosphines. AB - The first chiral phosphine-catalyzed activation of acrylates for intramolecular formal [2 + 4] reactions with unsaturated imines is described. The catalytic reactions afford N-heterocycles with exceptionally high diastereo- and enantioselectivities. The [2 + 4] products are amenable for further transformations to useful molecules such as chiral piperidines and multicyclic structures. PMID- 22676163 TI - The care of older people during and after disasters: a review of the recent experiences in Queensland, Australia and Christchurch, New Zealand. PMID- 22676164 TI - The Enhanced Primary Care program and falls prevention: perceptions of private occupational therapists and physiotherapists. AB - AIM: To investigate the processes involved for private occupational therapists (OTs) and physiotherapists (PTs) to implement Medicare items from the Enhanced Primary Care (EPC) program within their practice, for the purpose of falls prevention interventions for older people. METHODS: Qualitative study using a grounded theory approach employing semistructured interviews with five private occupational therapists and five private physiotherapists from across the Sydney area and the Hunter region. RESULTS: The following key themes emerged in relation to the potential for the EPC to be used to access falls prevention: (i) interdisciplinary communication and communication with consumers; (ii) best practice in community-based falls prevention using the EPC program; and (iii) administrative and organisational challenges of the EPC program. CONCLUSION: Participants supported the EPC program, and saw its potential for delivering falls prevention interventions in the community. However, findings suggest that the EPC program needs to be further refined to be more effective. PMID- 22676165 TI - Sex differences in the use of complementary and alternative medicine in older men and women. AB - AIM: The aim of this study was to examine sex differences in complementary and alternative medicine (CAM) use among older adults. METHODS: Cross-sectional analysis of data from two cohort studies of community-dwelling women (n = 5399) and men (n = 3188) aged 82-87 and 77-91 years, respectively. The main outcome measure was self-report of consultations with an alternative health practitioner. RESULTS: Men were 1.79 (95% confidence interval (CI): 1.46, 2.20) times more likely to use CAM than women. People born in a non-English speaking country were 1.49 times (95% CI: 0.94, 2.35) more likely to use CAM. Self-reported general health (P = 0.01) and bodily pain (P < 0.01) were significantly associated with CAM use. CONCLUSION: In contrast to previous research, CAM use is more prevalent among older men than older women in our sample. Both men and women are using CAM to maintain good health and for the treatment of ongoing conditions. PMID- 22676166 TI - Rates of hospitalisations and mortality of older adults admitted with burn injuries in Western Australian from 1983 to 2008. AB - AIM: To estimate temporal trends in burn injury hospitalisations, mortality and hospital stay, for older adults with a burn-related hospitalisation. METHODS: De identified data of all incident burn hospitalisations for adults 60 years and older in Western Australia from 1983-2008 were analysed. Poisson regression analyses were used to estimate temporal trends in hospital admissions and mortality. Zero truncated negative binomial regression analysis was used to identify factors associated with hospital stay. RESULTS: Between 1983 and 2008, hospitalisation rates increased for scalds (incident rate ratio (IRR) 1.01, 95% CI: 1.00-1.02) and contact burns (IRR 1.05, 95% CI: 1.03-1.07) while a significant reduction in flame hospitalisation rates (IRR 0.93, 95% CI: 0.92 0.94) was estimated. No significant changes in length of stay or burn-related mortality were estimated. CONCLUSIONS: Burn safety and prevention strategies that include first aid education need to be developed that target older adults living in their homes, to decrease their risk of sustaining burn injuries. PMID- 22676167 TI - Staying safe at home. Home environmental audit recommendations and uptake in an older population at high risk of falling. AB - AIM: To identify the level of uptake of occupational therapists' home environmental audit recommendations by older community dwellers and the factors that contribute to adherence. METHODS: DESIGN AND SETTING: Cohort nested within an RCT that compared two models of care for fall prevention located in Brisbane, Australia. PARTICIPANTS: Community-dwelling older people >60 at risk of falls (n = 80). INTERVENTIONS: An environmental audit and recommendations by an occupational therapist. RESULTS: Of the recommendations made, 55% were completed by 6 months. Increasing number of comorbidities was a significant predictor of adherence with recommendations. Recommendations requiring external providers were more likely to be completed than those relying on the client or family member. CONCLUSION: Occupational therapists need to consider a wide range of intrinsic and extrinsic factors, which may contribute to adherence with home modifications. PMID- 22676168 TI - Media reports on dementia: quality and type of messages in Australian media. AB - AIM: To analyse changes in the quantity and quality of media reporting about dementia in Australian media between two time periods. METHODS: A media retrieval service collected all news items related to dementia. Quality ratings based on previously developed criteria were made for a stratified random sample of items - 1129 items for 2000/2001 and 1606 for 2006/2007. Nine items of quality were assessed. A summary score for quality was constructed. The content of the sampled media items was also coded. RESULTS: Overall, the mean total quality score for dementia-related items significantly improved over the study period. There were very large improvements in quality of reporting of 'sensationalism', 'language' and 'provision of information about help services' and some small deterioration in quality for 'medical terminology' and 'illness versus person'. CONCLUSIONS: A very positive finding here is that generally the quality of reporting dementia has improved over the period studied. PMID- 22676169 TI - Development of a Computerised Antithrombotic Risk Assessment Tool (CARAT) to optimise therapy in older persons with atrial fibrillation. AB - AIM: To develop and evaluate a novel Computerised Antithrombotic Risk Assessment Tool (CARAT) to aid clinicians' decision making regarding the risk-benefit of antithrombotic therapy in older patients. METHODS: CARAT was developed in an iterative process involving multidisciplinary feedback and computerisation of previously trialled algorithms. Hospital-based clinicians then applied the tool to patient cases, to evaluate its usability. RESULTS: Overall, 94% of clinicians (n= 27 yielding 216 responses) were satisfied with CARAT's format. Most (72%) clinician responses agreed with CARAT recommendations; over two-thirds agreed with estimates of stroke and bleeding risk. However, geriatricians were 3.5 times more likely to disagree with CARAT recommendations than cardiologists, particularly in cases of high fall risk. Overall, 63% responded that CARAT was at least 'somewhat useful' for clinical practice; 22% indicating it was 'very useful'. CONCLUSION: CARAT has potential as a useful decision-support tool to assist clinicians in decision making regarding appropriate antithrombotic therapy in older patients. PMID- 22676171 TI - Attitudes towards health-care robots in a retirement village. AB - AIM: This study investigated the attitudes and preferences of staff, residents and relatives of residents in a retirement village towards a health-care robot. METHODS: Focus groups were conducted with residents, managers and caregivers, and questionnaires were collected from 32 residents, 30 staff and 27 relatives of residents. RESULTS: The most popular robot tasks were detection of falls and calling for help, lifting, and monitoring location. Robot functionality was more important than appearance. Concerns included the loss of jobs and personal care, while perceived benefits included allowing staff to spend quality time with residents, and helping residents with self-care. Residents showed a more positive attitude towards robots than both staff and relatives. CONCLUSIONS: These results provide an initial guide for the tasks and appearance appropriate for a robot to provide assistance in aged care facilities and highlight concerns. PMID- 22676170 TI - Undertreatment of osteoporosis in regional Western Australia. AB - AIM: To identify the geographic differences in osteoporosis management. METHODS: In this cross-sectional study, osteoporosis treatments in older patients presented to a hip fracture unit from mid 2005-2009 were analysed. Logistic regression was used to examine the association of rural residency with osteoporosis treatments. RESULTS: Among 1130 patients (20% rural, mean age 81.1 years), there was a low prescription rate for osteoporosis among rural patients. Rural patients were 65% less likely to use vitamin D, 60% less likely to use calcium and 46% less likely to use bisphosphonates before a hip fracture than their urban counterparts. Their compliance with vitamin D and calcium was also lower at 1 year but improved significantly over the study period, whereas compliance with bisphosphonate decreased in both regions. CONCLUSION: Undertreatment of osteoporosis was common in rural patients. These findings need to be confirmed by larger population-based studies. PMID- 22676172 TI - Loneliness and self-reported health among older persons in New Zealand. AB - AIM: The purpose of this study was to identify the rate, degree and impact of loneliness in a sample of 332 older community-dwelling New Zealanders. METHODS: A cross-sectional survey was used to collect self-reported data on loneliness, physical and mental health, age, sex and marital status. Eight per cent of the sample was found to be severely lonely, 44% moderately lonely and 48% not lonely. Participants were assigned to three groups by level of loneliness and compared on age, sex, marital status and health. RESULTS: The groups were found to differ on physical (F [2,329] = 5.3, P = 0.006) and mental health (F [2,329] = 13.7, P < 0.001) but not on age, sex or marital status. CONCLUSIONS: Those who were in the severely and moderately lonely groups scored lower on both health measures than those in the not lonely group. PMID- 22676173 TI - Oxidative stress and metabolic syndrome in a Japanese female population. AB - AIM: One of the methods to evaluate oxidative stress in clinical medical settings is the reactive oxygen metabolites (d-ROMs) test. While metabolic syndrome (MetS) is considered an oxidative condition, the oxidative status in MetS has not been fully examined using this test. The aim of the present study was to investigate the possible association between oxidative stress as evaluated by the d-ROMs test and the MetS component number, in a Japanese female population. METHODS: The serum oxidant capacity (measured by the d-ROMs test) was cross-sectionally determined in cardiovascular disease-free and non-smoking women who were not taking medications (n = 180; mean age, 60 +/- 10 (standard deviation) years). Their MetS state was determined by the National Cholesterol Education Program Adult Treatment Panel recommendations with minor modifications for a Japanese population. RESULTS: Patients with MetS (n = 60, 362 +/- 53 CARR U) showed a significantly higher oxidant capacity by d-ROMs than those without MetS (n = 120, 324 +/- 55 CARR U, P < 0.01). Moreover, the significant increase in the oxidant capacity by d-ROMs was closely associated with an increase in the MetS component number (trend P < 0.01). CONCLUSIONS: These results showed a significantly positive association between the oxidant capacity (by d-ROMs) and the MetS component number in this population. Further studies are required to establish the clinical applications of this test to MetS practice and clarify the biological mechanisms of the observed relationships. PMID- 22676174 TI - Regulatory influences on general practitioner service delivery in residential aged care. PMID- 22676176 TI - Australian Association of Gerontology: Position Statement--research priorities in housing for older Australians. PMID- 22676177 TI - Measurement and analysis of electromagnetic pollution generated by GSM-900 mobile phone networks in Erciyes University, Turkey. AB - Mobile phones are becoming increasingly important in our everyday lives. The rising number of mobile phones reflects a similar increase in the number of base stations. Because of this rapid evolution, the establishment and planning of new base stations has become mandatory. However, the rise in the number of base stations, in terms of human health, is potentially very harmful. It is important to analyze the radiation levels of base stations until we can confirm that they are definitely not harmful in the long term. Mapping of electromagnetic field (EMF) is also important from a medical point of view because it provides useful information, for example, on the detection of diseases caused by EMF. With the help of this information the distribution of diseases over different regions can be obtained. In this article, the electromagnetic radiation levels of base stations were measured at 80 different points in Erciyes University (ERU), Turkey and detailed information about the measurement tools and measurement method were given. It was observed that no area in ERU exceeded the national and international limits. It is also observed that the effects of base stations vary according to duration and degree of exposure. Therefore, if people are exposed to a very low-intensity electromagnetic field for a very long time, serious health problems can occur. PMID- 22676178 TI - Children with juvenile idiopathic arthritis: are health outcomes better for those diagnosed younger? AB - BACKGROUND: Children living with juvenile idiopathic arthritis (JIA) have swollen, painful and stiff joints, which may have an impact on all spheres of their life, as well as their family. While children diagnosed in their preschool years may be at risk for worse physical outcomes than children diagnosed later in life, it is not clear whether they have worse psychological outcomes and whether these outcomes have an impact on their everyday life. The aim of this study was to examine the association between age at diagnosis and health outcomes in families of children with JIA. METHODS: Parents of children with JIA (n = 182) who attended rheumatology clinics at the Montreal Children's Hospital and British Columbia Children's Hospital completed measures assessing socio-demographic attributes, their child's health status, health-related quality of life and pain level, as well as their own level of psychological distress and coping behaviours. Regression models explored the association between age at diagnosis and health outcomes while adjusting for sex, age, severity and duration of the disease. RESULTS: Parents of children diagnosed with JIA before 5 years of age found their child to have a better health-related quality of life in terms of psychosocial functioning than parents of children diagnosed later [beta = -0.91 ( 1.63, -0.19)]. Children diagnosed younger were also found to be less limited in schoolwork or activities with friends because of emotional or behavioural problems than children diagnosed later [odds ratio = 0.07 (0.01, 0.42)]. CONCLUSIONS: Children diagnosed younger seem to show good psychosocial adjustment, which may also be true for their caregivers. Perhaps more attention to psychosocial adjustment should be given to families of children who are diagnosed with the disease at an older age. PMID- 22676179 TI - In vivo imaging of proteasome inhibition using a proteasome-sensitive fluorescent reporter. AB - A proteasome degrades numerous regulatory proteins that are critical for tumor growth and is therefore recognized as a promising anticancer target. Determining proteasome activity in the tumors of mice bearing xenografts is essential for the development of novel proteasome inhibitors. We developed a system for in vivo imaging of proteasome inhibition in the tumors of living mice, using a proteasome sensitive fluorescent reporter, ZsProSensor-1. This reporter consists of a green fluorescent protein, ZsGreen, fused to mouse ornithine decarboxylase, which is degraded by the proteasome without being ubiquitinated. In stably transfected cells expressing ZsProSensor-1, the fluorescent reporter was rapidly degraded under steady-state conditions, whereas it was stabilized in the presence of proteasome inhibitors. Subcutaneous inoculation of the transfected cells into nude mice resulted in tumor formation. When the proteasome inhibitor bortezomib was intravenously administered to mice bearing these tumors, the ZsProSensor-1 protein accumulated in the tumors and emitted a fluorescent signal in a dose dependent manner. Robust fluorescence was sustained for 3 days and then gradually decreased to baseline levels within 15 days. Intravenous administration of bortezomib also showed potent antitumor activity. In contrast, oral administration of bortezomib did not result in fluorescent protein accumulation in tumors or exhibit any antitumor activity. These results indicate that in vivo imaging using the ZsProSensor-1 fluorescent protein can be used as an indicator of antitumor activity and will be a powerful tool for the development of novel proteasome inhibitors. PMID- 22676180 TI - Phacoemulsification combined with posterior capsulorhexis and anterior vitrectomy in the management of malignant glaucoma in phakic eyes. AB - PURPOSE: To describe sequential phacoemulsification-intraocular lens (IOL) implantation-posterior capsulorhexis-anterior vitrectomy in the management of phakic malignant glaucoma. METHODS: Twenty consecutive patients (25 eyes) with phakic malignant glaucoma were enrolled at the Zhongshan Ophthalmic Center, Sun Yat-sen University. All patients underwent phacoemulsification, IOL implantation and posterior capsulorhexis together with anterior vitrectomy via a clear corneal paracentesis. Visual acuity, intraocular pressure (IOP), anterior chamber depth (ACD), surgical complications and medications required after the surgery were recorded. RESULTS: After surgery, the mean LogMAR visual acuity and ACD increased significantly (visual acuity from -1.56 +/- 1.17 to -0.54 +/- 0.81, p < 0.001; ACD from 0.367 +/- 0.397 mm to 2.390 +/- 0.575 mm, p < 0.001), and mean IOP decreased significantly (from 39.6 +/- 10.6 mm Hg to 14.5 +/- 4.1 mmHg, p < 0.001). No serious perioperative complications occurred, and only five eyes required topical glaucoma medications after surgery. CONCLUSION: Combined phacoemulsification-IOL implantation-posterior capsulorhexis-anterior vitrectomy surgery is a safe and effective method for treating patients with phakic malignant glaucoma. PMID- 22676182 TI - Risk factors for Mycoplasma genitalium infection among female sex workers: a cross-sectional study in two cities in southwest China. AB - BACKGROUND: Mycoplasma genitalium (MG) is one of the common causes of non gonococcal urethritis (NGU) in men and is associated with cervicitis, endometritis, and pelvic inflammatory diseases (PID) in women. The prevalence of MG infection has been reported to be high among female sex workers (FSWs) in many countries, but limited information is known among this population in China. METHODS: From July to September 2009, venue-based FSWs were recruited in two cities (Wuzhou and Hezhou) of Guangxi Autonomous Region in southwest China. Information of socio-demographic and behavioral characteristics was collected by a questionnaire-based interview. Cervical specimens were obtained for detection of MG using a real-time polymerase chain reaction (PCR) assay targeting mgpA gene. RESULTS: The overall prevalence of MG infection among 810 FSWs was 13.2% (95% CI = 10.87%-15.52%). MG infection was significantly associated with less education (adjusted odds ratio (AOR) = 2.36, 95% CI = 1.15-4.87) consisting of junior high school or below, being single (AOR = 2.27, 95% CI = 1.42-3.62), migrant background (AOR = 2.03, 95% CI = 1.29-3.20), and absence of any STI symptoms in the previous year (AOR = 1.66, 95% CI = 1.09-2.52). CONCLUSIONS: MG infection was prevalent among FSWs in the study areas. This pattern of infection suggests that an increasing attention should be paid to MG screening and treatment in this high risk population. PMID- 22676184 TI - A thematic review of scientific and family interests in Canavan Disease: where are the developmentalists? AB - BACKGROUND: Canavan Disease is a degenerative neurological condition resulting in a spongy deterioration of the brain. Much research has been conducted by the medical community regarding this condition, but little research can be found in the psychological literature. METHOD: A review of the scientific literature related to Canavan Disease using the Psychinfo and PubMed databases was conducted covering a 5-year span from 2006 through 2011. Concurrently, a review of parent initiated topics found on the most popular Canavan Disease Internet discussion board was conducted for comparison purposes. RESULTS: When comparing the topics discussed and information sought among parents with the themes noted in the extant scientific literature, researchers found an exceedingly small overlap between the two communities of interest. In the scientific literature, published research on Canavan Disease focused on three areas: the biochemistry of Canavan Disease, diagnosis and genetic counselling, and clinical therapeutic approaches in Canavan Disease. Of the 42 unique topics raised on a popular Internet discussion board, however, only three (7%) fell into the category of diagnosis and genetic counselling, none (0%) fell into the category of the biochemistry of Canavan Disease, and four fell into the category of clinical therapeutic approaches in Canavan Disease (10%). Of the four posts addressing clinical therapeutic approaches to Canavan Disease, only one post truly overlapped with the topics addressed by the scientific community. Worded differently, while these three categories comprise 100% of the extant scientific literature regarding Canavan Disease, they comprise only 17% of the parent-raised topics. The remaining 83% of parent-raised topics addressed concerns not currently being focusing upon by the scientific community, namely, non-medical practical issues, information regarding specific characteristics of Canavan Disease, non-medical developmental and quality of life issues, and day-to-day developmental and medical concerns. CONCLUSION: By comparing the extant literature on Canavan Disease with the topics of interest raised by parents and caregivers, it seems clear that there is a significant 'underlap' of topics raised by these two communities of interest, one that may reflect a lack of sensitivity on the part of the scientific community to meet the needs of this population of knowledge seekers. It is the suggestion of these authors that developmental psychology may be the appropriate scientific field within which to address this need and fill this gap in the current literature. PMID- 22676183 TI - Genes associated with MUC5AC expression in small airway epithelium of human smokers and non-smokers. AB - BACKGROUND: Mucus hypersecretion contributes to the morbidity and mortality of smoking-related lung diseases, especially chronic obstructive pulmonary disease (COPD), which starts in the small airways. Despite progress in animal studies, the genes and their expression pattern involved in mucus production and secretion in human airway epithelium are not well understood. We hypothesized that comparison of the transcriptomes of the small airway epithelium of individuals that express high vs low levels of MUC5AC, the major macromolecular component of airway mucus, could be used as a probe to identify the genes related to human small airway mucus production/secretion. METHODS: Flexible bronchoscopy and brushing were used to obtain small airway epithelium (10th to 12th order bronchi) from healthy nonsmokers (n=60) and healthy smokers (n=72). Affymetrix HG-U133 plus 2.0 microarrays were used to assess gene expression. Massive parallel sequencing (RNA-Seq) was used to verify gene expression of small airway epithelium from 5 nonsmokers and 6 smokers. RESULTS: MUC5AC expression varied 31 fold among the healthy nonsmokers. Genome-wide comparison between healthy nonsmokers (n = 60) grouped as "high MUC5AC expressors" vs "low MUC5AC expressors" identified 528 genes significantly up-regulated and 15 genes significantly down-regulated in the high vs low expressors. This strategy identified both mucus production and secretion related genes under control of a network composed of multiple transcription factors. Based on the literature, genes in the up-regulated list were used to identify a 73 "MUC5AC-associated core gene" list with 9 categories: mucus component; mucus-producing cell differentiation-related transcription factor; mucus-producing cell differentiation-related pathway or mediator; post-translational modification of mucin; vesicle transport; endoplasmic reticulum stress-related; secretory granule associated; mucus secretion-related regulator and mucus hypersecretory-related ion channel. As a validation cohort, we assessed the MUC5AC-associated core gene list in the small airway epithelium of an independent set of healthy smokers (n = 72). There was up-regulation of MUC5AC in the small airway epithelium of smokers (2.3-fold, p < 10-8) associated with a coordinated up-regulation of MUC5AC associated core gene expression pattern in the small airway epithelium of smokers (p < 0.01). Deep sequencing confirmed these observations. CONCLUSION: The identification of the genes associated with increased airway mucin production in humans should be useful in understanding the pathogenesis of airway mucus hypersecretion and identifying therapeutic targets. AUTHOR SUMMARY: Mucus hypersecretion contributes to the morbidity and mortality of smoking-related lung diseases, especially chronic obstructive pulmonary disease (COPD), which starts in the small airways. Little is known about the gene networks associated with the synthesis and secretion of mucins in the human small airway epithelium. Taking advantage of the knowledge that MUC5AC is a major mucin secreted by the small airway epithelium, the expression of MUC5AC in small airway epithelium is highly regulated at the transcriptional level and our observation that healthy nonsmokers have variable numbers of MUC5AC+ secretory cells in the human small airway epithelium, we compared genome-wide gene expression of the small airway epithelium of high vs low MUC5AC expressors from 60 nonsmokers to identify the genes associated with MUC5AC expression. This novel strategy enabled identification of a 73 "MUC5AC-associated core gene" list with 9 categories, which control a series of processes from mucin biosynthesis to mucus secretion. The coordinated gene expression pattern of MUC5AC-associated core genes were corroborated in an independent cohort of 72 healthy smokers. Deep sequencing of small airway epithelium RNA confirmed these observations. This finding will be useful in identifying therapeutic targets to treat small airway mucus hypersecretion. PMID- 22676185 TI - Association of the MTHFR gene with antipsychotic-induced metabolic abnormalities in patients with schizophrenia. PMID- 22676186 TI - Impact of IL28B SNPs on therapeutic outcome and liver histology differs between hepatitis C virus genotypes. PMID- 22676187 TI - Accuracy of NAT2 SNP genotyping panels to infer acetylator phenotypes in African, Asian, Amerindian and admixed populations. PMID- 22676190 TI - Clinical trial evidence of the promise of pharmacogenomics warfarin dosing algorithms. PMID- 22676191 TI - Institutional profile: The Carney Centre for Pharmacogenomics: a New Zealand focus for personalized medicine research. AB - The integration of genetics and genomics with pharmacology and clinical medicine has enriched our understanding of all of these disciplines and is steadily providing a more complete picture of the etiology, pathophysiology and treatment of disease. To capitalize on this new knowledge requires the ability to evaluate the underlying evidence base and to test the utility of any proposed pharmacogenetic or genomic approaches to personalized medicine, within local or regional healthcare structures. The Carney Centre for Pharmacogenomics is now in its eighth year of operation, and although small by international standards, it has proven to be a valuable focus for research, training and dissemination of such knowledge in New Zealand and beyond. By focusing predominantly on research and training, the center has raised awareness about the value and limitations of pharmacogenetics and pharmacogenomic approaches. PMID- 22676192 TI - Retrospective evidence for clinical validity of expanded genetic model in warfarin dose optimization in a South Indian population. AB - AIM: To optimize warfarin dose in patients at risk for thrombotic events, we have recently developed a pharmacogenomic algorithm, which explained 44.9% of the variability in warfarin dose requirements using age, gender, BMI, vitamin K intake, CYP2C9 (*2 and *3) and VKORC1 (*3, *4 and -1639 G>A) as predictors. The aim of the current study is to develop an expanded genetic model that can explain greater percentage of warfarin variability and that has clinical validity. PATIENTS & METHODS: CYP2C9*8, CYP4F2 V433M, GGCX G8016A and thyroid status were added to an expanded genetic model (n = 243). RESULTS: The expanded genetic model explained 61% of the variability in warfarin dose requirements, has a prediction accuracy of +/-11 mg/week and can differentiate warfarin sensitive and warfarin resistant groups efficiently (areas under receiver operating characteristic curves: 0.93 and 0.998, respectively; p < 0.0001). Higher percentage of International Normalized Ratios in therapeutic range (52.68 +/- 4.21 vs 43.80 +/- 2.27; p = 0.04) and prolonged time in therapeutic range (61.74 +/- 3.18 vs 47.75 +/- 5.77; p = 0.03) were observed in subjects with a prediction accuracy of <1 mg/day compared with subjects with prediction accuracy >1 mg/day. In the warfarin resistant group, primary hypothyroidism was found to induce more resistance while in the warfarin-sensitive group, hyperthyroidism was found to increase sensitivity. CONCLUSION: The expanded genetic model explains greater variability in warfarin dose requirements and it prolongs time in therapeutic range and minimizes out-of-range International Normalized Ratios. Thyroid status also influences warfarin dose adjustments. PMID- 22676193 TI - UGT2B7 genetic polymorphisms are associated with the withdrawal symptoms in methadone maintenance patients. AB - AIM: To test whether the genetic polymorphisms within the gene encoding the UGT2B7 gene may have an impact on methadone treatment. MATERIALS & METHODS: Twelve SNPs in UGT2B7 were selected. 366 methadone maintenance treatment patients in Taiwan were recruited and genotyped. RESULTS: In a genotype recessive model, rs6600879, rs6600880, rs4554144, rs11940316, rs7438135, rs7662029, rs7668258, rs7439366, rs4292394 and rs6600893 showed significant associations with severity of withdrawal symptoms (permutation p < 0.002), pupil size (permutation p < 0.048) and tremor (permutation p < 0.008). Haplotypes of GATCAGCCGC and CTCTGATTCT were significantly associated with pupil size score and tremor score (p < 0.034). CONCLUSION: These results suggest that SNPs of the UGT2B7 gene may play important roles in opiate withdrawal symptoms. PMID- 22676194 TI - Impact of the UGT1A1*28 allele on response to irinotecan: a systematic review and meta-analysis. AB - AIM: Pre-emptive irinotecan dose reduction for UGT1A1*28 homozygotes may result in reduced risk of severe neutropenia and diarrhea. However, clinical utility and cost-effectiveness are dependent upon such a dose reduction not impacting irinotecan efficacy. Whether UGT1A1*28 genotype is associated with irinotecan response therefore is an important gap in existing knowledge to inform clinical utility. MATERIALS & METHODS: A systematic review and meta-analysis was performed to analyze the difference in objective response rate (ORR) between irinotecan administered cancer patients with different UGT1A1*28 genotypes: *28/*28 (homozygous variant), *1/*28 (heterozygous variant) or *1/*1 (wild-type). The effect of irinotecan dose on the association between UGT1A1*28 and ORR was also assessed. RESULTS: Differences in ORR for either of the genotype comparisons, *28/*28 versus *1/*1 and *1/*28 versus *1/*1, were not statistically significant. Irinotecan dose also did not impact upon ORR differences between UGT1A1 genotype groups. CONCLUSION: An individual's response to irinotecan is unlikely to be affected by UGT1A1*28 status. PMID- 22676195 TI - Next-generation sequencing and large genome assemblies. AB - The next-generation sequencing (NGS) revolution has drastically reduced time and cost requirements for sequencing of large genomes, and also qualitatively changed the problem of assembly. This article reviews the state of the art in de novo genome assembly, paying particular attention to mammalian-sized genomes. The strengths and weaknesses of the main sequencing platforms are highlighted, leading to a discussion of assembly and the new challenges associated with NGS data. Current approaches to assembly are outlined and the various software packages available are introduced and compared. The question of whether quality assemblies can be produced using short-read NGS data alone, or whether it must be combined with more expensive sequencing techniques, is considered. Prospects for future assemblers and tests of assembly performance are also discussed. PMID- 22676196 TI - A systematic review of the A118G (Asn40Asp) variant of OPRM1 in relation to smoking initiation, nicotine dependence and smoking cessation. AB - Candidate gene studies on smoking behaviors mainly focused on dopaminergic and serotonergic genes, but genes within the u-opioid system might also be involved. The A118G variant within the OPRM1 gene has been most often examined in relation to smoking, yielding inconsistent findings. It is largely unknown which of the alleles increases susceptibility for smoking behaviors. The aim of this review was to merge findings of OPRM1 gene studies in relation to smoking behaviors and to elaborate on the underlying biological mechanism of the A118G variant. It appeared that A118 was more likely to increase susceptibility to smoking behaviors than 118G, especially with regard to nicotine dependence, but less with smoking initiation and cessation. The proposed functioning of the OPRM1 gene is further explained. PMID- 22676197 TI - Return of research results from pharmacogenomic versus disease susceptibility studies: what's drugs got to do with it? AB - One of the most controversial ethical issues in genomics research is the return of individual research results to research subjects. As new technologies, including whole-genome sequencing, provide an increased opportunity for researchers to find clinically relevant research results, the questions related to if, when and how individual research results should be returned become more central to the ethical conduct of genomic research. In the absence of federal guidance on this issue, many groups and individuals have developed recommendations and suggestions to address these questions. Most of these recommendations have focused on the return of individual results from disease susceptibility studies. However, in addition to predicting the development of disease, genomic research also includes predicting an individual's response to drugs, especially the risk of developing adverse events. This article evaluates and compares the return of individual research results from disease susceptibility studies versus pharmacogenomic studies. PMID- 22676198 TI - CYP2D6*11 and challenges in clinical genotyping of the highly polymorphic CYP2D6 gene. AB - CYP2D6 is genotyped clinically for prediction of response to tamoxifen, psychotropic drugs and other medications. Phenotype prediction is dependent upon accurate genotyping. The CYP Allele Nomenclature Committee maintains the allelic nomenclature for CYP2D6; however, in some cases, the list of polymorphisms associated with a given allele is incomplete. Clinical laboratories and in vitro diagnostic manufacturers rely upon this nomenclature, in addition to the literature, to infer allelic function and haplotypes and when they design CYP2D6 testing platforms. This article provides more complete sequencing data for the CYP2D6*11 allele and describes the difficulties encountered in genotyping CYP2D6 when incomplete data are available. The CYP Allele Nomenclature Committee should provide clear information about the completeness of the original data used to define each allele. PMID- 22676199 TI - Exploratory planning and implementation of a pilot pharmacogenetic program in a community pharmacy. AB - AIM: To describe the exploratory planning and implementation of a pilot pharmacogenetic program in a community pharmacy. An institutional review board approved protocol for a clopidogrel pharmacogenetic program in a community pharmacy was developed to address feasibility and evaluate the pilot program. STUDY CONCEPT: Subjects taking clopidogrel are asked to participate at the point of medication dispensing. A pharmacist schedules an appointment with subjects to discuss the study and collects a buccal swab sample for CYP2C19 testing. When the results are available, the pharmacist consults with the subject's prescriber regarding test result interpretation and associated recommendations, and schedules a second appointment with the participant to discuss results and review any physician-approved therapeutic changes. The intervention-associated consultation is then billed to the subject's insurance. RESULTS: Subject enrollment has begun. CONCLUSION: Community pharmacists may be valuable partners in pharmacogenetics. PMID- 22676200 TI - Copy number variation and gene rearrangements in CYP2D6 genotyping using multiplex ligation-dependent probe amplification in Koreans. AB - AIM: The present study introduces a simple method for CYP2D6 genotyping that not only determines the heterozygous or homozygous deletions and duplications, but also distinguishes tandem hybrids. MATERIALS & METHODS: Using two commercially available methods, 49 Korean male subjects were genotyped for CYP2D6. The Affymetrix((r)) Targeted Human Drug Metabolizing Enzymes and Transporter 1.0 Assay was used for SNP genotyping and multiplex ligation-dependent probe amplification (MLPA) assay (SALSA((r)) MLPA((r)) Kit P128-A1 CYP450) was used for copy number analysis. Long range PCR was used to confirm the MLPA results. Fifty Caucasian samples obtained from the Coriell Institute were used to confirm the accuracy of the MLPA assay. RESULTS: Using two commercially available methods, we found seven different allele types with CYP2D6*1 (34.7%), *2 (12.2%), *10 (17.4%) and *36-*10 (22.5%) being the most common alleles in the Korean population. The MLPA results showed 100% agreement with long-range-PCR results and were able to distinguish deletions and duplications among 50 Caucasian reference samples. CONCLUSION: The application of MLPA-based genotyping to routine clinical analysis will enable patients to be assigned to more accurate genotypes at a reasonable cost in a large number of individuals at the majority of locations. PMID- 22676202 TI - Anti-hyperalgesic effects of calcitonin on neuropathic pain interacting with its peripheral receptors. AB - BACKGROUND: The polypeptide hormone calcitonin is clinically well known for its ability to relieve neuropathic pain such as spinal canal stenosis, diabetic neuropathy and complex regional pain syndrome. Mechanisms for its analgesic effect, however, remain unclear. Here we investigated the mechanism of anti hyperalgesic action of calcitonin in a neuropathic pain model in rats. RESULTS: Subcutaneous injection of elcatonin, a synthetic derivative of eel calcitonin, relieved hyperalgesia induced by chronic constriction injury (CCI). Real-time reverse transcriptase-polymerase chain reaction analysis revealed that the CCI provoked the upregulation of tetrodotoxin (TTX)-sensitive Nav.1.3 mRNA and downregulation of TTX-resistant Nav1.8 and Nav1.9 mRNA on the ipsilateral dorsal root ganglion (DRG), which would consequently increase the excitability of peripheral nerves. These changes were reversed by elcatonin. In addition, the gene expression of the calcitonin receptor and binding site of 125I-calcitonin was increased at the constricted peripheral nerve tissue but not at the DRG. The anti-hyperalgesic effect and normalization of sodium channel mRNA by elcatonin was parallel to the change of the calcitonin receptor expression. Elcatonin, however, did not affect the sensitivity of nociception or gene expression of sodium channel, while it suppressed calcitonin receptor mRNA under normal conditions. CONCLUSIONS: These results suggest that the anti-hyperalgesic action of calcitonin on CCI rats could be attributable to the normalization of the sodium channel expression, which might be exerted by an unknown signal produced at the peripheral nerve tissue but not by DRG neurons through the activation of the calcitonin receptor. Calcitonin signals were silent in the normal condition and nerve injury may be one of triggers for conversion of a silent to an active signal. PMID- 22676203 TI - Vegetarian diet and mental disorders: results from a representative community survey. AB - BACKGROUND: The present study investigated associations between vegetarian diet and mental disorders. METHODS: Participants were drawn from the representative sample of the German Health Interview and Examination Survey and its Mental Health Supplement (GHS-MHS). Completely vegetarian (N = 54) and predominantly vegetarian (N = 190) participants were compared with non-vegetarian participants (N = 3872) and with a non-vegetarian socio-demographically matched subsample (N = 242). RESULTS: Vegetarians displayed elevated prevalence rates for depressive disorders, anxiety disorders and somatoform disorders. Due to the matching procedure, the findings cannot be explained by socio-demographic characteristics of vegetarians (e.g. higher rates of females, predominant residency in urban areas, high proportion of singles). The analysis of the respective ages at adoption of a vegetarian diet and onset of a mental disorder showed that the adoption of the vegetarian diet tends to follow the onset of mental disorders. CONCLUSIONS: Vegetarian diet is associated with an elevated risk of mental disorders. However, there was no evidence for a causal role of vegetarian diet in the etiology of mental disorders. PMID- 22676204 TI - Challenges to fair decision-making processes in the context of health care services: a qualitative assessment from Tanzania. AB - BACKGROUND: Fair processes in decision making need the involvement of stakeholders who can discuss issues and reach an agreement based on reasons that are justifiable and appropriate in meeting people's needs. In Tanzania, the policy of decentralization and the health sector reform place an emphasis on community participation in making decisions in health care. However, aspects that can influence an individual's opportunity to be listened to and to contribute to discussion have been researched to a very limited extent in low-income settings. The objective of this study was to explore challenges to fair decision-making processes in health care services with a special focus on the potential influence of gender, wealth, ethnicity and education. We draw on the principle of fairness as outlined in the deliberative democratic theory. METHODS: The study was carried out in the Mbarali District of Tanzania. A qualitative study design was used. In depth interviews and focus group discussion were conducted among members of the district health team, local government officials, health care providers and community members. Informal discussion on the topics was also of substantial value. RESULTS: The study findings indicate a substantial influence of gender, wealth, ethnicity and education on health care decision-making processes. Men, wealthy individuals, members of strong ethnic groups and highly educated individuals had greater influence. Opinions varied among the study informants as to whether such differences should be considered fair. The differences in levels of influence emerged most clearly at the community level, and were largely perceived as legitimate. CONCLUSIONS: Existing challenges related to individuals' influence of decision making processes in health care need to be addressed if greater participation is desired. There is a need for increased advocacy and a strengthening of responsive practices with an emphasis on the right of all individuals to participate in decision-making processes. This simultaneously implies an emphasis on assuring the distribution of information, training and education so that individuals can participate fully in informed decision making. PMID- 22676205 TI - Effects of a regular walking exercise program on behavioral and biochemical aspects in elderly people with type II diabetes. AB - The present study examined the effects of a regular walking exercise program on behavioral (daily physical activity, physical strength, energy consumption) and biochemical (fasting blood glucose [FBG], glycated hemoglobin [HbA1c], total cholesterol, triglycerides [TG], low-density lipoprotein cholesterol, and high density lipoprotein cholesterol) aspects of elderly people with type II diabetes. A randomized and stratified experimental design was used with experimental and control groups. The experimental group was subjected to a 6 month walking exercise program, involving walking exercise three times per week for 50 min, and a 4 week education program on diet control and the prevention of complications, once per week for 20 min. Post-test was conducted after 3 and 6 months to examine short- and long-term behavioral and biochemical effects. The regular walking exercise program effectively increased daily physical activity, physical strength, and energy consumption (behavioral aspects), and decreased FBG, HbA1c, and TG levels (biochemical aspects) in elderly people with type II diabetes. The incidence of type II diabetes complications might be reduced by implementing a regular walking exercise program. PMID- 22676207 TI - Left atrial systolic force and outcome in asymptomatic mild to moderate aortic stenosis. AB - BACKGROUND AND AIMS: In patients with chronic pressure overload due to hypertension or aortic valve stenosis (AS), higher left atrial systolic force (LASF) is associated with a high-risk cardiovascular (CV) phenotype. We tested LASF as prognostic marker in patients with AS. METHODS: We used baseline and outcome data from 1,566 patients recruited in the Simvastatin and Ezetimibe in AS (SEAS) study evaluating the effect of placebo-controlled simvastatin and ezetimibe treatment on CV events. The primary outcome was a composite of major CV events, including CV death, aortic valve replacement, nonfatal myocardial infarction, hospitalization for unstable angina, heart failure caused by progression of AS, coronary artery bypass grafting, percutaneous coronary intervention, and nonhemorrhagic stroke. LASF was calculated by Manning's method. High LASF was defined as >95th percentile (50 Kdynes/cm(2)) of the distribution within the study population. RESULTS: During 4.3 years of follow-up, a major CV event occurred in 38 of 78 patients with high LASF (49%) and in 513 of 1,488 (34%) with normal LASF (P = 0.01). In multivariate Cox regression analysis, high LASF predicted higher rate of major CV events (Hazard ratio 1.43 [95% confidence interval 1.01-2.03] independent of aortic valve area and LV mass index. A simple risk score including absence or presence of these three variables allowed risk stratification into low, intermediate, high and very high risk for major CV events during follow-up (22%, 28%, 38%, and 53%, respectively). CONCLUSIONS: Higher LASF provides additional prognostic information in patients with asymptomatic mild-to-moderate AS. PMID- 22676206 TI - Enhanced nerve-stimulated muscarinic and neurokinin contractions of ileum from streptozotocin guinea-pigs. AB - Diabetes mellitus can lead to neuropathy of enteric neurons, resulting in abnormal gut motility. These studies investigated voltage-dependent contributions of muscarinic M3 receptor activation by acetylcholine and neurokinin NK1 receptor activation by neurokinins to nerve-stimulated contractions of longitudinal ileal strips from STZ guinea-pigs, a type 1 diabetic model with insulin deficiency, but mild hyperglycaemia. Contractions to bethanechol, substance P methyl ester, and nerve stimulation were greater in diabetic as compared to control ileum. The muscarinic M3 receptor antagonist 4-DAMP at lower voltages and the neurokinin NK1 receptor antagonist SR140333 at higher voltages, but not the neurokinin NK1 receptor antagonist CP-96,345, were more effective at inhibiting nerve-stimulated immediate peak contractions and total areas of contraction of ileum from diabetic as compared to control animals. For diabetic ileum, voltage-dependent increases in the areas of nerve-stimulated contraction were observed in the presence of 4 DAMP and CP-96,345 but not SR140333. At low voltages only, nerve-stimulated release of acetylcholine was greater from diabetic as compared to control ileum. Fluorescence intensity of tachykinin-like immunoreactivity was increased in ileal myenteric ganglia from diabetic as compared to control animals. In diabetic guinea-pigs, stronger ileal nerve-stimulated contractions reflected increased release of acetylcholine at lower voltages and tachykinins at higher voltages, as well as increased sensitivity of smooth muscle M3 and NK1 receptors to acetylcholine and tachykinins. Hypoinsulinaemia may be a primary contributor to intestinal motility dysfunction in type 1 diabetes mellitus. PMID- 22676209 TI - Gd13Fe10C13: indications of Fe-Fe multiple bonding emerging from chemical frustration. AB - We report the synthesis and crystal structure of the carbide Gd(13)Fe(10)C(13). This compound adopts a new structure type that is remarkable for its "H"-shaped C(2)FeFeC(2) units, which have some of the shortest Fe-Fe contacts known. A bonding analysis using DFT-calibrated Huckel calculations hints that Fe-Fe multiple bonding underlies these short distances. Gd(13)Fe(10)C(13) undergoes ferromagnetic ordering at ~55 K. PMID- 22676208 TI - Emotional impact of genetic trials in progressive paediatric disorders: a dose ranging exon-skipping trial in Duchenne muscular dystrophy. AB - BACKGROUND: Gene-modifying trials offer hope for improvement in chronic paediatric disorders, but they may also lead to disappointment and have an adverse emotional effect on families. This study aimed to examine emotional impact on participants in a paediatric exon-skipping trial. METHODS: Nineteen male children with Duchenne muscular dystrophy (DMD), and their parents, taking part in a dose-ranging study of an i.v. administered morpholino splice-switching oligomer (which can restore the reading frame in DMD and induce dystrophin expression) underwent a psychosocial/psychiatric examination at trial entry. Emotional impact was assessed at trial completion using questionnaires. RESULTS: The mean child age was 8.9 years (SD 2.1); 13(68%) were attending mainstream school. Most families were well adjusted psychosocially at trial entry. Post trial median child emotional impact scores were 5/10 (n= 18), but impact was rated as positive by 6/14 (42%), neutral/mixed by 5 (35%) and negative by 3 (21%). Median post-trial psychosocial/psychiatric change scores in children and parents were minimal. Actual post-trial negative impact was statistically significantly associated with higher expected impact at trial entry, at which time the families of the three children displaying actual negative impact reported higher family stress levels in combination with a variety of other psychosocial risks factors. CONCLUSIONS: In carefully selected families with low levels of psychosocial stress/distress at trial entry, and with good support from paediatric research units (including psychiatric input when required), genetic trials in progressive disorders such as DMD can have a predominantly positive or neutral emotional impact. Nevertheless, negative impact is reported by a minority of families and possible psychosocial predictors deserving further scrutiny have been identified. PMID- 22676210 TI - Design, synthesis, and biological evaluation of novel disubstituted dibenzosuberones as highly potent and selective inhibitors of p38 mitogen activated protein kinase. AB - Synthesis, biological testing, structure-activity relationships (SARs), and selectivity of novel disubstituted dibenzosuberone derivatives as p38 MAP kinase inhibitors are described. Hydrophilic moieties were introduced at the 7-, 8-, and 9-position of the 2-phenylamino-dibenzosuberones, improving physicochemical properties as well as potency. Extremely potent inhibitors were obtained, with half-maximal inhibitory concentration (IC(50)) values in the low nM range in a whole blood assay measuring the inhibition of cytokine release. The high potency of the target compounds together with the outstanding selectivity of this novel class of compounds toward p38 mitogen activated protein (MAP) kinase as compared to other kinases indicate them to be most applicable as tools in pharmacological research and eventually they may foster a new generation of anti-inflammatory drugs. PMID- 22676211 TI - Locally reinforced polymer-based composites for elastic electronics. AB - A promising approach to fabricating elastic electronic systems involves processing thin film circuits directly on the elastic substrate by standard photolithography. Thin film devices are generally placed onto stiffer islands on the substrate surface to protect devices from excessive strain while still achieving a globally highly deformable system. Here we report a new method to achieve island architectures by locally reinforcing polymeric substrates at the macro- and microscale using magnetically responsive anisotropic microparticles. We demonstrate that the resulting particle-reinforced elastic substrates can be made smooth enough for the patterning and successful operation of thin film transistors with transfer characteristics comparable to state-of-the-art devices. PMID- 22676212 TI - Effects of extremely low-frequency pulsed electromagnetic fields on morphological and biochemical properties of human breast carcinoma cells (T47D). AB - This study was carried out to investigate the effects of 100 and 217 Hz extremely low-frequency pulsed electromagnetic fields (ELF-PEMF) on cell proliferation, actin reorganization, and ROS generation in a human breast carcinoma cells (T47D). Cells were exposed for 24-72 h, at 100 and 217 Hz, 0.1 mT. The treatment induced a time dependent decrease in cell growth after 72 h and revealed an increase in fluorescence intensity in cytoplasm and actin aggregations around the nucleus as detected by fluorescence microscopy. The amount of actin in T47D cells increased after 48 h exposure to 100 Hz and 24 h to 217 Hz while no changes in nuclear morphology were detected. Exposing the cells to 217 Hz for 72 h caused a dramatically increase of intracellular ROS generation while with exposure to 100 Hz it remained nearly unchanged. These results suggest that exposure to ELF-PEMF (100, 217 Hz, 0.1 mT) are able inducing an increase of actin level, its migration toward nucleus but despite of these changes and dramatically increase in ROS generation the symptoms of apoptosis were not observed. Our results support the hypothesis that cell response to EMF may only be observed at certain window effects; such as frequency and intensity of EMF parameters. PMID- 22676213 TI - A new reimbursement system for innovative pharmaceuticals combining value-based and free market pricing. AB - Sweden has experienced a national value-based pricing (VBP) system for innovative outpatient drugs operated by the Pharmaceutical Benefits Board - LFN (now called the Dental and Pharmaceutical Benefits agency - TLV) since 2002. VBP has the character of a monopoly system, leading to reimbursement decisions where usage of new medicines is limited to subgroups and not the population for which the drug is approved. VBP relies on a broad societal perspective, encouraging innovations by signaling to firms that value-adding treatments are demanded. However, the VBP system is operated without a drug budget responsibility. The budget responsibility lies at the regional level, not operating VBP, thus an intrinsic conflict is built into the system. The aim of this article is to suggest a modification to the current reimbursement system in Sweden where payment for pharmaceuticals is split between the regional and national levels. The system is expected to make new innovative pharmaceuticals accessible to a larger number of patients and provide more consumer surplus without reducing the producer surplus. In short, the county councils pay the marginal cost of production while the state pays for the innovation. PMID- 22676217 TI - Upcoming New Feature in the Journal of Biomolecular Structure & Dynamics. PMID- 22676214 TI - A (1)H and (13)C NMR Study on the Role of Salt-Bridges in the Formation of a Type I beta-Turn in N-Acetyl-L-Asp-L-Glu-L-Lys-L-Ser-NH(2). AB - Abstract The conformation of the tetrapeptide N-Acetyl-Asp(7)-Glu(8)-Lys(9) Ser(10)-NH(2), a fragment of the type I collagen alpha-1 chain N-telopeptide, has been studied by (1)H and (13)C NMR and circular dichroism spectroscopy. The spectroscopic evidence, based on two-dimensional, phase-sensitive NMR techniques such as COSY, ROESY, proton-carbon shift correlation and selective COLOC, indicates a strong dependence of the conformation on the experimental conditions. In CD(3)OH/H(2)O (60/40) at ca. neutral pH the tetrapeptide forms a beta-turn, stabilized by a hydrogen bond between NH(S(10)) and CO(D(7)) and a strong salt bridge between COO(-)(E(8)) and NH(3) (+)(K(9)). The beta-turn is type I and appears to coexist with a non-hydrogen-bonded structure. The coexistence of these two conformers is proven by proton NMR data such as NH-NH ROEs, reduced NH H(alpha)(E(8)) coupling constant NH(E(8)) low-field shift and the temperature coefficient of NH(S(10)), whereas the conclusion regarding the salt-bridge is based on (13)C results. In the same solvent, at a pH below the pKa of the carboxyl groups, no evidence for a conformation other than extended can be found. In aqueous solution at approximately neutral pH, evidence for the E(8)-K(9) charge interaction is observed, but not for a hydrogen bond anywhere in the molecule. PMID- 22676222 TI - Abstracts from the 38th Nordic Congress of Obstetrics and Gynecology 17-19 June 2012, Bergen, Norway. PMID- 22676223 TI - Liver-intestine cadherin induction by epidermal growth factor receptor is associated with intestinal differentiation of gastric cancer. AB - Gastric cancer (GC) is one of the most common malignancies worldwide. The epidermal growth factor receptor (EGFR) molecule is very important in GC progression. To examine the correlation between EGFR and GC-related genes, we analyzed gene expression profiles of HT-29 cells treated with EGFR ligands and identified six genes upregulated by epidermal growth factor (EGF) and transforming growth factor (TGF)-alpha treatment. Among these, we focused on cadherin 17 (CDH17) encoding liver-intestine cadherin (LI-cadherin). Expression of LI-cadherin was induced by both EGF and TGF-alpha, as detected by quantitative RT-PCR and Western blot analysis. A luciferase assay showed that LI-cadherin promoter activity was enhanced by EGF or TGF-alpha in both HT-29 cells and MKN-74 GC cells. Immunohistochemical analysis of 152 GC cases showed that out of 58 LI cadherin-positive cases, 24 (41%) cases were also positive for EGFR, whereas out of 94 LI-cadherin-negative cases, only 9 (10%) cases were positive for EGFR (P < 0.0001). Double-immunofluorescence staining revealed that EGFR and LI-cadherin were coexpressed. Significant correlation was found between LI-cadherin expression and advanced T grade and N grade. Both EGFR and LI-cadherin expression were more frequently found in GC cases with an intestinal mucin phenotype than in cases with a gastric mucin phenotype. These results indicate that, in addition to the known intestinal transcription factor caudal type homeobox 2, EGFR activation induces LI-cadherin expression and participates in intestinal differentiation of GC. PMID- 22676224 TI - Closed-edged graphene nanoribbons from large-diameter collapsed nanotubes. AB - The diameter dependence of the collapse of single- and double-walled carbon nanotubes to two- and four-walled graphene nanoribbons with closed edges (CE(x)GNRs) has been experimentally determined and compared to theory. TEM and AFM were used to characterize nanotubes grown from preformed 4.0 nm diameter aluminum-iron oxide particles. Experimental data indicate that the energy equivalence point (the diameter at which the energy of a round and fully collapsed nanotube is the same) is 2.6 and 4.0 nm for single- and double-walled carbon nanotubes, respectively. Molecular dynamics simulations predict similar energy equivalence diameters with the use of epsilon = 54 meV/pair to calculate the carbon-carbon van der Waals interaction. PMID- 22676225 TI - Intervene before leaving: clustered lot quality assurance sampling to monitor vaccination coverage at health district level before the end of a yellow fever and measles vaccination campaign in Sierra Leone in 2009. AB - BACKGROUND: In November 2009, Sierra Leone conducted a preventive yellow fever (YF) vaccination campaign targeting individuals aged nine months and older in six health districts. The campaign was integrated with a measles follow-up campaign throughout the country targeting children aged 9-59 months. For both campaigns, the operational objective was to reach 95% of the target population. During the campaign, we used clustered lot quality assurance sampling (C-LQAS) to identify areas of low coverage to recommend timely mop-up actions. METHODS: We divided the country in 20 non-overlapping lots. Twelve lots were targeted by both vaccinations, while eight only by measles. In each lot, five clusters of ten eligible individuals were selected for each vaccine. The upper threshold (UT) was set at 90% and the lower threshold (LT) at 75%. A lot was rejected for low vaccination coverage if more than 7 unvaccinated individuals (not presenting vaccination card) were found. After the campaign, we plotted the C-LQAS results against the post-campaign coverage estimations to assess if early interventions were successful enough to increase coverage in the lots that were at the level of rejection before the end of the campaign. RESULTS: During the last two days of campaign, based on card-confirmed vaccination status, five lots out of 20 (25.0%) failed for having low measles vaccination coverage and three lots out of 12 (25.0%) for low YF coverage. In one district, estimated post-campaign vaccination coverage for both vaccines was still not significantly above the minimum acceptable level (LT = 75%) even after vaccination mop-up activities. CONCLUSION: C-LQAS during the vaccination campaign was informative to identify areas requiring mop-up activities to reach the coverage target prior to leaving the region. The only district where mop-up activities seemed to be unsuccessful might have had logistical difficulties that should be further investigated and resolved. PMID- 22676226 TI - The role of lipooligosaccharide phosphorylcholine in colonization and pathogenesis of Histophilus somni in cattle. AB - Histophilus somni is a Gram-negative bacterium and member of the Pasteurellaceae that is responsible for respiratory disease and other systemic infections in cattle. One of the bacterium's virulence factors is antigenic phase variation of its lipooligosaccharide (LOS). LOS antigenic variation may occur through variation in composition or structure of glycoses or their substitutions, such as phosphorylcholine (ChoP). However, the role of ChoP in the pathogenesis of H. somni disease has not been established. In Haemophilus influenzae ChoP on the LOS binds to platelet activating factor on epithelial cells, promoting bacterial colonization of the host upper respiratory tract. However, ChoP is not expressed in the blood as it also binds C-reactive protein, resulting in complement activation and killing of the bacteria. In order to simulate the susceptibility of calves with suppressed immunity due to stress or previous infection, calves were challenged with bovine herpes virus-1 or dexamethazone 3 days prior to challenge with H. somni. Following challenge, expression of ChoP on the LOS of 2 different H. somni strains was associated with colonization of the upper respiratory tract. In contrast, lack of ChoP expression was associated with bacteria recovered from systemic sites. Histopathology of cardiac tissue from myocarditis revealed lesions containing bacterial clusters that appeared similar to a biofilm. Furthermore, some respiratory cultures contained substantial numbers of Pasteurella multocida, which were not present on preculture screens. Subsequent biofilm experiments have shown that H. somni and P. multocida grow equally well together in a biofilm, suggesting a commensal relationship may exist between the two species. Our results also showed that ChoP contributed to, but was not required for, adhesion to respiratory epithelial cells. In conclusion, expression of ChoP on H. somni LOS contributed to colonization of the bacteria to the host upper respiratory tract, but phase variable loss of ChoP expression may help the bacteria survive systemically. PMID- 22676227 TI - Neurological soft signs in persons with amnestic mild cognitive impairment and the relationships to neuropsychological functions. AB - BACKGROUND: Neurological abnormalities have been reported in people with amnestic mild cognitive impairment (aMCI). The current study aimed to examine the prevalence of neurological soft signs (NSS) in this clinical group and to examine the relationship of NSS to other neuropsychological performances. METHODS: Twenty nine people with aMCI and 28 cognitively healthy elderly people were recruited for the present study. The NSS subscales (motor coordination, sensory integration, and disinhibition) of the Cambridge Neurological Inventory and a set of neuropsychological tests were administered to all the participants. RESULTS: People with aMCI exhibited significantly more motor coordination signs, disinhibition signs, and total NSS than normal controls. Correlation analysis showed that the motor coordination subscale score and total score of NSS were significantly inversely correlated with the combined Z-score of neuropsychological tests in aMCI group. CONCLUSIONS: These preliminary findings suggested that people with aMCI demonstrated a higher prevalence of NSS compared to healthy elderly people. Moreover, NSS was found to be inversely correlated with the neuropsychological performances in persons with aMCI. When taken together, these findings suggested that NSS may play a potential important role and serve as a tool to assist in the early detection of aMCI. PMID- 22676228 TI - Commentary: Childhood exposure to environmental adversity and the well-being of people with intellectual disabilities. AB - People with intellectual disabilities have poorer health than their non-disabled peers. They are also more likely to be exposed to a wide range of environmental adversities in childhood. Research undertaken in the general population has demonstrated that exposure to environmental adversity in childhood can have an adverse impact on health and well-being across the life course. Recently, research in this area has added new breadth and depth to our understanding of: (1) the extent to which cumulative exposure to environmental adversities across the life course, but especially in early childhood, can reduce health and well being; (2) the social, psychological and biological mediating pathways through which environmental adversities may impair health; (3) the processes associated with resilience and vulnerability in the face of exposure to adversity; and (4) the social significance of these effects in accounting for the magnitude of the inequalities in health that are apparent both between and within populations. This new knowledge is making a significant contribution to the development of social policies that seek to combine health gain with the reduction in health inequalities. This paper attempts to apply this knowledge to research aimed at understanding and improving the health and well-being of people with intellectual disabilities. PMID- 22676229 TI - Relation between smoking history and gene expression profiles in lung adenocarcinomas. AB - BACKGROUND: Lung cancer is the worldwide leading cause of death from cancer. Tobacco usage is the major pathogenic factor, but all lung cancers are not attributable to smoking. Specifically, lung cancer in never-smokers has been suggested to represent a distinct disease entity compared to lung cancer arising in smokers due to differences in etiology, natural history and response to specific treatment regimes. However, the genetic aberrations that differ between smokers and never-smokers' lung carcinomas remain to a large extent unclear. METHODS: Unsupervised gene expression analysis of 39 primary lung adenocarcinomas was performed using Illumina HT-12 microarrays. Results from unsupervised analysis were validated in six external adenocarcinoma data sets (n=687), and six data sets comprising normal airway epithelial or normal lung tissue specimens (n=467). Supervised gene expression analysis between smokers and never-smokers were performed in seven adenocarcinoma data sets, and results validated in the six normal data sets. RESULTS: Initial unsupervised analysis of 39 adenocarcinomas identified two subgroups of which one harbored all never-smokers. A generated gene expression signature could subsequently identify never-smokers with 79-100% sensitivity in external adenocarcinoma data sets and with 76-88% sensitivity in the normal materials. A notable fraction of current/former smokers were grouped with never-smokers. Intriguingly, supervised analysis of never smokers versus smokers in seven adenocarcinoma data sets generated similar results. Overlap in classification between the two approaches was high, indicating that both approaches identify a common set of samples from current/former smokers as potential never-smokers. The gene signature from unsupervised analysis included several genes implicated in lung tumorigenesis, immune-response associated pathways, genes previously associated with smoking, as well as marker genes for alveolar type II pneumocytes, while the best classifier from supervised analysis comprised genes strongly associated with proliferation, but also genes previously associated with smoking. CONCLUSIONS: Based on gene expression profiling, we demonstrate that never-smokers can be identified with high sensitivity in both tumor material and normal airway epithelial specimens. Our results indicate that tumors arising in never-smokers, together with a subset of tumors from smokers, represent a distinct entity of lung adenocarcinomas. Taken together, these analyses provide further insight into the transcriptional patterns occurring in lung adenocarcinoma stratified by smoking history. PMID- 22676230 TI - Tracking of accelerometry-measured physical activity during childhood: ICAD pooled analysis. AB - BACKGROUND: Understanding of physical activity (PA) tracking during childhood is important to predict PA behaviors and design appropriate interventions. We compared tracking of PA according to PA level and type of day (weekday/weekend) in a pool of five children's cohort studies. METHODS: Data from ALSPAC, CLAN, Iowa Bone Development Study, HEAPS, PEACH were extracted from the International Children's Accelerometry Database (ICAD), resulting in 5,016 participants with age, gender, and accelerometry data at both baseline and follow-up (mean age: 10.3 years at baseline, 12.5 years at follow-up). Daily minutes spent in moderate and vigorous-intensity PA (MVPA) and vigorous-intensity PA (VPA) was categorized into quintiles. Multinomial logistic regression models were fit to predict follow up (M)VPA from baseline (M)VPA (reference: 20- < 80%tile), age at follow-up, and follow-up duration. RESULTS: For the weekday, VPA tracking for boys with high baseline VPA was higher than boys with low baseline VPA (ORs: 3.9 [95% CI: 3.1, 5.0] vs. 2.1 [95% CI: 1.6, 2.6]). Among girls, high VPA was less stable when compared low VPA (ORs: 1.8 [95% CI: 1.4, 2.2] vs. 2.6 [95% CI: 2.1, 3.2]). The pattern was similar for MVPA among girls (ORs: 1.6 [95% CI: 1.2, 2.0] vs. 2.8 [95% CI: 2.3, 3.6]). Overall, tracking was lower for the weekend. CONCLUSIONS: PA tracking was higher on the weekday than the weekend, and among inactive girls than active girls. The PA "routine" of weekdays should be used to help children establish healthy PA patterns. Supports for PA increase and maintenance of girls are needed. PMID- 22676232 TI - Trialkylphosphine-stabilized copper(I) gallium(III) phenylchalcogenolate complexes: crystal structures and generation of ternary semiconductors by thermolysis. AB - A series of organometallic trialkylphosphine-stabilized copper gallium phenylchalcogenolate complexes [(R(3)P)(m)Cu(n)Me(2-x)Ga(EPh)(n+x+1)] (R = Me, Et, (i)Pr, (t)Bu; E = S, Se, Te; x = 0, 1) has been prepared and structurally characterized by X-ray diffraction. From their molecular structures three groups of compounds can be distinguished: ionic compounds, ring systems, and cage structures. All these complexes contain one gallium atom bound to one or two methyl groups, whereas the number of copper atoms, and therefore the nuclearity of the complexes, is variable and depends mainly on size and amount of phosphine ligand used in synthesis. The Ga-E bonds are relatively rigid, in contrast to flexible Cu-E bonds. The lengths of the latter are controlled by the coordination number and steric influences. The Ga-E bond lengths depend systematically on the number of methyl groups bound to the gallium atom, with somewhat shorter bonds in monomethyl compounds compared to dimethyl compounds. Quantum chemical computations reproduce this trend and show furthermore that the rotation of one phenyl group around the Ga-E bond is a low energy process with two distinct minima, corresponding to two different conformations found experimentally. Mixtures of different types of chalcogen atoms on molecular scale are possible, and then ligand exchange reactions in solution lead to mixed site occupation. In thermogravimetric studies the complexes were converted into the ternary semiconductors CuGaE(2). The thermolysis reaction is completed at temperatures between 250 and 400 degrees C, typically with lower temperatures for the heavier chalcogens. Because of significant release of Me(3)Ga during the thermolysis process, and especially in case of copper excess in the precursor complexes, binary copper chalcogenides are obtained as additional thermolysis products. Quaternary semiconductors can be obtained from mixed chalcogen precursors. PMID- 22676231 TI - Single blood-Hg samples can result in exposure misclassification: temporal monitoring within the Japanese community (United States). AB - BACKGROUND: The most prominent non-occupational source of exposure to methylmercury is the consumption of fish. In this study we examine a fish consuming population to determine the extent of temporal exposure and investigate the extent to which single time estimates of methylmercury exposure based on blood-Hg concentration can provide reliable estimates of longer-term average exposure. METHODS: Blood-mercury levels were obtained from a portion of the Arsenic Mercury Intake Biometric Study (AMIBS) cohort. Specifically, 56 Japanese women residing in the Puget Sound area of Washington State, US were sampled on three occasions across a one-year period. RESULTS: An average of 135 days separated samples, with mean blood-mercury levels for the visits being 5.1, 6.6 and 5.0 MUg/l and geometric means being 2.7, 4.5 and 3.1 MUg/l. The blood-mercury levels in this group exceed national averages with geometric means for two of the visits being between the 90th and 95th percentiles of nationally observed levels and the lowest geometric mean being between the 75th and 90th percentile. Group means were not significantly different across sampling periods suggesting that exposure of combined subjects remained relatively constant. Comparing intra individual results over time did not reveal a strong correlation among visits (r = 0.19, 0.50, 0.63 between 1st and 2nd, 2nd and 3rd, and 1st and 3rd sample results, respectively). In comparing blood-mercury levels across two sampling interval combinations (1st and 2nd, 2nd and 3rd, and 1st and 3rd visits, respectively), 58% (n = 34), 53% (n = 31) and 29% (n = 17) of the individuals had at least a 100% difference in blood-Hg levels. CONCLUSIONS: Point estimates of blood-mercury, when compared with three sample averages, may not reflect temporal variability and individual exposures estimated on the basis of single blood samples should be treated with caution as indicators of long-term exposure. Reliance on single blood samples can make predicting ongoing methylmercury exposure highly speculative due to the large intra-individual variability. PMID- 22676233 TI - Fine mapping of hepatitis B virus pre-S deletion and its association with hepatocellular carcinoma. AB - BACKGROUND: Naturally occurring pre-S deletion mutants have been identified in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). AIMS: This study investigated whether specific deletions within the pre-S region were associated with HCC development. METHODS: The virologic characteristics of 56 HBV chronic carriers and 112 age-matched patients with HBV-related HCC were examined. RESULTS: The HCC patients had a significantly higher frequency of high viral load, basal core promoter mutation and pre-S deletion than chronic carriers. Sequencing analysis showed that the deleted regions were clustered mainly in the C terminus of pre-S1 (70.5%) and the N terminus of pre-S2 (72.7%) in HCC patients. Immuno-epitope mapping of these pre-S deletion sequences showed that all the deletion regions encompassed T- and B- cell epitopes and the B-cell epitope at amino acid 1-6 of pre-S2 was significantly deleted in HCC patients (60.0% vs. 0.0%; P = 0.036). Functional mapping of these deletion mutants showed that most of HCC patients lost one or more functional sites and the deletion of site for viral secretion (aa 1-5 of pre-S2 domain) was significantly detected in HCC patients than chronic carriers (62.5% vs. 0.0%; P = 0.029). Computational protein function prediction indicated that these mutants may have different molecular functions and participate in other biological processes compared with wild-type pre-S. CONCLUSIONS: Deletion of B-cell epitope at amino acid 1-6 of pre S2 region and the site for virion secretion are significantly associated with the development of HCC in HBV carriers. PMID- 22676234 TI - Descriptive survey of Summer Genetics Institute nurse graduates in the USA. AB - The purpose of this study was to describe the clinical, research, educational, and professional activities that nurses are engaged in following participation in a 2 month intramural genetics training program. An online survey was administered in 2010 to graduates of the program sponsored by the US National Institute of Nursing Research from 2000 to 2009, in Bethesda, Maryland, USA. The electronic, voluntary survey was sent to 189 graduates via email. The survey included demographic characteristics, educational preparation, professional roles and responsibilities, and attitudes about genetic testing and privacy issues. Of the 95 graduates responding to the survey, 74% had doctorates and 70% were advanced practice nurses. All respondents reported incorporating genetics knowledge into daily clinical, academic, or research practices since completing the program, with 72% reporting being involved in genetically-focused research (52% with research funding), 32% incorporating genetics into patient care, and 79% providing genetics education. Respondents working in a hospital setting or academic institution were more likely to desire additional training in genetics. National Institute of Nursing Research graduates have successfully integrated genomics into a variety of nursing practices. PMID- 22676235 TI - Evaluation of cardiac involvement with mediastinal lymphoma: the role of innovative integrated cardiovascular imaging. AB - A 73-year-old woman presented in right heart failure. Computed tomography of the chest revealed a 3 cm * 5 cm anterior mediastinal mass. Contrast-enhanced two dimensional transthoracic echocardiography, cardiac magnetic resonance imaging (MRI), positron emission tomography (PET), and MRI-PET fusion demonstrated invasion of the pericardium and right heart by the tumor. Mediastinal biopsy revealed high-grade diffuse large B-cell lymphoma, which responded to chemotherapy. The role of each modality in this case was discussed in the manuscript. In conclusion, the integration of multiple imaging modalities is extremely useful in the characterization, localization, diagnosis and treatment of an unusual cardiac mass. PMID- 22676236 TI - Involvement of ASR genes in aluminium tolerance mechanisms in rice. AB - Among cereal crops, rice is considered the most tolerant to aluminium (Al). However, variability among rice genotypes leads to remarkable differences in the degree of Al tolerance for distinct cultivars. A number of studies have demonstrated that rice plants achieve Al tolerance through an unknown mechanism that is independent of root tip Al exclusion. We have analysed expression changes of the rice ASR gene family as a function of Al treatment. The gene ASR5 was differentially regulated in the Al-tolerant rice ssp. Japonica cv. Nipponbare. However, ASR5 expression did not respond to Al exposure in Indica cv. Taim rice roots, which are highly Al sensitive. Transgenic plants carrying RNAi constructs that targeted the ASR genes were obtained, and increased Al susceptibility was observed in T1 plants. Embryogenic calli of transgenic rice carrying an ASR5 green fluorescent protein fusion revealed that ASR5 was localized in both the nucleus and cytoplasm. Using a proteomic approach to compare non-transformed and ASR-RNAi plants, a total of 41 proteins with contrasting expression patterns were identified. We suggest that the ASR5 protein acts as a transcription factor to regulate the expression of different genes that collectively protect rice cells from Al-induced stress responses. PMID- 22676238 TI - Nanodiamond promotes surfactant-mediated triglyceride removal from a hydrophobic surface at or below room temperature. AB - We demonstrate that ca. 5 nm nanodiamond particles dramatically improve triglyceride lipid removal from a hydrophobic surface at room temperature using either anionic or nonionic surfactants. We prepare nanodiamond-surfactant colloids, measure their stability by dynamic light scattering and use quartz crystal microbalance-dissipation, a technique sensitive to surface mass, in order to compare their ability to remove surface-bound model triglyceride lipid with ionic and nonionic aqueous surfactants at 15-25 degrees C. Oxidized, reduced, omega-alkylcarboxylic acid, and omega-alkylamidoamine surface-modified adducts are prepared, and then characterized by techniques including (13)C cross polarization (CP) magic-angle spinning (MAS) NMR. Clear improvement in removal of triglyceride was observed in the presence of nanodiamond, even at 15 degrees C, both with nanodiamond-surfactant colloids, and by prior nanoparticle deposition on interfacial lipid, showing that nanodiamonds are playing a crucial role in the enhancement of the detergency process, providing unique leads in the development of new approaches to low-temperature cleaning. PMID- 22676237 TI - Multifunctional Fe3O4/TaO(x) core/shell nanoparticles for simultaneous magnetic resonance imaging and X-ray computed tomography. AB - Multimodal imaging is highly desirable for accurate diagnosis because it can provide complementary information from each imaging modality. In this study, a sol-gel reaction of tantalum(V) ethoxide in a microemulsion containing Fe(3)O(4) nanoparticles (NPs) was used to synthesize multifunctional Fe(3)O(4)/TaO(x) core/shell NPs, which were biocompatible and exhibited a prolonged circulation time. When the NPs were intravenously injected, the tumor-associated vessel was observed using computed tomography (CT), and magnetic resonance imaging (MRI) revealed the high and low vascular regions of the tumor. PMID- 22676242 TI - Assessment of environmental factors in disabled children 2-12 years: development and reliability of the Craig Hospital Inventory of Environmental Factors (CHIEF) for Children-Parent Version. AB - BACKGROUND: Children with disabilities and their families experience environmental barriers in the school and community environments. There is a need to understand and appropriately measure environmental factors that influence activity and participation for disabled children. The purpose of this paper is to describe the adaptation process of the Craig Hospital Inventory of Environmental Factors (CHIEF) to make it suitable as a parent proxy measure for disabled children aged 2-12 years. METHODS: The adaptation process consisted of four steps using data from previous research conducted at CanChild: (i) analysis of item total correlations from all items on the CHIEF; (ii) frequency of endorsement; (iii) determination of the representativeness of the questions; and (iv) correlations on selected items. Once the items were selected, a test-retest reliability study was conducted. RESULTS: The internal consistencies (alpha) for the time 1 and time 2 administrations were 0.76 and 0.78, respectively. Test retest reliability of the questionnaire was ICC = 0.73 for the total product score. CONCLUSION: The 10-item CHIEF for Children-Parent Version is an acceptable, easy-to-complete and reliable measure of perceived environmental barriers for disabled children 2-12 years of age. PMID- 22676243 TI - Factors associated with and causes of perinatal mortality in northeastern Tanzania. AB - OBJECTIVE: To identify factors associated with perinatal mortality in northeastern Tanzania. DESIGN: Prospective cohort study. SETTING: Northeastern Tanzania. Population. 872 mothers and their newborns. METHODS: Pregnant women were screened for factors possibly associated with perinatal mortality, including preeclampsia, small-for-gestational age, preterm delivery, anemia, and health seeking behavior. Fetal growth was monitored using ultrasound. Finally, the specific causes of the perinatal deaths were evaluated. MAIN OUTCOME MEASURE: Perinatal mortality. RESULTS: Forty-six deaths occurred. Key factors associated with perinatal mortality were preterm delivery (adjusted odds ratio (OR) 14.47, 95% confidence interval (CI) 3.23-64.86, p < 0.001), small-for-gestational age (adjusted OR 3.54, 95%CI 1.18-10.61, p = 0.02), and maternal anemia (adjusted OR 10.34, 95%CI 1.89-56.52, p = 0.007). Adherence to the antenatal care program (adjusted OR 0.027, 95%CI 0.003-0.26, p = 0.002) protected against perinatal mortality. The cause of death in 43% of cases was attributed to complications related to labor and specifically to intrapartum asphyxia (30%) and neonatal infection (13%). Among the remaining deaths, 27% (7/26) were attributed to preeclampsia and 23% (6/26) to small-for-gestational age. Of these, 54% (14/26) were preterm. CONCLUSIONS: Preeclampsia, small-for-gestational age and preterm delivery were key risk factors and causes of perinatal mortality in this area of Tanzania. Maternal anemia was also strongly associated with perinatal mortality. Furthermore, asphyxia accounted for a large proportion of the perinatal deaths. Interventions should target the prevention and handling of these conditions in order to reduce perinatal mortality. PMID- 22676244 TI - A conative educational model for an intervention program in obese youth. AB - BACKGROUND: Obesity in children has increased in recent years throughout the world and is associated with adverse health consequences. Early interventions, including appropriate pedagogy strategies, are important for a successful intervention program. The aim of this study was to assess changes in body mass index, the ability to perform sport activities, behavior in the classroom and academic performance following one year of a health-wellness intervention program in obese youth. METHODS: The CEMHaVi program included 37 obese children (19 girls and 18 boys). Participants received an intervention program consisting of physical activity and health education. Assessment included body mass index, academic performance, classroom performance and ability to perform sport activities. Paired t tests were used to assess the effects of intervention, and chi square was used to assess inter-action between measures. RESULTS: Findings of the study suggest significant decrease in Z scores of Body Mass Index and an improvement of academic performance, classroom behavior and the ability to perform sport activities (p < 0.05). Chi square testing showed significant positive inter-actions between body mass index, classroom behavior and academic performance. CONCLUSIONS: Results following year one of CEMHaVi showed that a program of physical activity and health education had positive effects on obesity, behavior in the classroom and the ability to perform sport activities in obese adolescents. Significant inter-action in changes between variables was observed. Findings are important for designing intervention models to improve health in obese youth. PMID- 22676245 TI - Randomized phase II study of three doses of oral TAS-108 in postmenopausal patients with metastatic breast cancer. AB - This randomized phase II study was intended to identify the optimal dose of TAS 108, a novel steroidal antiestrogen, for the treatment of breast cancer in postmenopausal Japanese women. The potential clinical effects of TAS-108 on the uterus, bone, serum lipids, and hormones were also investigated. Postmenopausal women with hormone receptor-positive metastatic breast cancer who had previously received one or two endocrine therapies were randomly assigned to one of the three possible dose levels of TAS-108 (40, 80 or 120 mg/day). Oral TAS-108 was given daily, and the efficacy and safety of the three doses were evaluated. A total of 97 patients (33, 32, and 32 in the 40-, 80-, and 120-mg groups, respectively) were treated with TAS-108. The clinical benefit rate was 30.3% for the 40-mg, 25.0% for the 80-mg, and 25.0% for the 120-mg group. The 40-mg group achieved the prespecified target threshold. TAS-108 at all dose levels was well tolerated and appeared to have no harmful effects in terms of the variables examined in this study. We conclude that the optimal dose of TAS-108 among the three doses is 40 mg, once daily, for further studies. JAPIC Clinical Trials Information number: Japic CTI - 121754. PMID- 22676247 TI - Synthesis and biological evaluation of 1-benzylidene-3,4-dihydronaphthalen-2-one as a new class of microtubule-targeting agents. AB - A series of 1-benzylidene-3,4-dihydronaphthalen-2-one derivatives were designed and synthesized, and their biological activities in vitro and in vivo were evaluated. The results showed a number of the title compounds exhibiting potent nanomolar activity in several human cancer cell lines. Of these, compound 22b showed the strongest inhibitory activity against human CEM, MDA-MBA-435, and K562 cells (IC(50) = 1 nM), displayed in vitro inhibition of tubulin polymerization (IC(50) = 3.93 MUM), and significantly induced cell cycle arrest in G2/M phase. In addition, compound 22b could inhibit the tumor growth in colon nude mouse xenograft tumor model significantly and seemed safer than CA-4 when achieving a similar tumor suppression. This study provided a new molecular scaffold for the further development of antitumor agents that target tubulin. PMID- 22676246 TI - Improved strategy for phylogenetic analysis of classical swine fever virus based on full-length E2 encoding sequences. AB - Molecular epidemiology has proven to be an essential tool in the control of classical swine fever (CSF) and its use has significantly increased during the past two decades. Phylogenetic analysis is a prerequisite for virus tracing and thus allows implementing more effective control measures. So far, fragments of the 5'NTR (150 nucleotides, nt) and the E2 gene (190 nt) have frequently been used for phylogenetic analyses. The short sequence lengths represent a limiting factor for differentiation of closely related isolates and also for confidence levels of proposed CSFV groups and subgroups. In this study, we used a set of 33 CSFV isolates in order to determine the nucleotide sequences of a 3508-3510 nt region within the 5' terminal third of the viral genome. Including 22 additional sequences from GenBank database different regions of the genome, comprising the formerly used short 5'NTR and E2 fragments as well as the genomic regions encoding the individual viral proteins Npro, C, Erns, E1, and E2, were compared with respect to variability and suitability for phylogenetic analysis. Full length E2 encoding sequences (1119 nt) proved to be most suitable for reliable and statistically significant phylogeny and analyses revealed results as good as obtained with the much longer entire 5'NTR-E2 sequences. This strategy is therefore recommended by the EU and OIE Reference Laboratory for CSF as it provides a solid and improved basis for CSFV molecular epidemiology. Finally, the power of this method is illustrated by the phylogenetic analysis of closely related CSFV isolates from a recent outbreak in Lithuania. PMID- 22676248 TI - The effect of ultrapro or prolene mesh on postoperative pain and well-being following endoscopic Totally Extraperitoneal (TEP) hernia repair (TULP): study protocol for a randomized controlled trial. AB - BACKGROUND: The purpose of this study was to describe the rationale and design of a randomized controlled trial analyzing the effects of mesh type (Ultrapro versus Prolene mesh) on postoperative pain and well-being following an endoscopic Totally Extraperitoneal (TEP) repair for inguinal hernias (short: TULP trial). METHODS AND DESIGN: The TULP trial is a prospective, two arm, double blind, randomized controlled trial to assess chronic postoperative pain and quality of life following implantation of a lightweight (Ultrapro) and heavyweight (Prolene) mesh in endoscopic TEP hernia repair. The setting is a high-volume single center hospital, specializing in TEP hernia repair. All patients are operated on by one of four surgeons. Adult male patients (>=18 years of age) with primary, reducible, unilateral inguinal hernias and no contraindications for TEP repair are eligible for inclusion in the study. The primary outcome is substantial chronic postoperative pain, defined as moderate to severe pain persisting >= 3 months postoperatively (Numerical Rating Scale, NRS 4-10). Secondary endpoints are the individual development of pain until three years after the TEP procedure, the quality of life (QoL), recurrence rate, patient satisfaction and complications. DISCUSSION: Large prospective randomized controlled studies with a long follow-up evaluating the incidence of chronic postoperative pain following implantation of lightweight and heavyweight mesh in endoscopic (TEP) hernia repair are limited. By studying the presence of pain and quality of life, but also complications and recurrences in a large patient population, a complete efficiency and feasibility assessment of both mesh types in TEP hernia repair will be performed. TRIAL REGISTRATION: The TULP study is registered in the Dutch Trial Register (NTR2131). PMID- 22676249 TI - Association between type 2 diabetes and chronic arsenic exposure in drinking water: a cross sectional study in Bangladesh. AB - BACKGROUND: Chronic exposure to high level of inorganic arsenic in drinking water has been associated with Type 2 Diabetes (T2D). Most research has been ecological in nature and has focused on high levels of arsenic exposure with few studies directly measuring arsenic levels in drinking water as an index of arsenic exposure. The effect of low to moderate levels of arsenic exposure on diabetes risk is largely unknown thus our study is adding further knowledge over previous works. METHODS: This cross sectional study was conducted in 1004 consenting women and men from 1682 eligible participants yielding a participation rate of 60%. These participants are aged >30 years and were living in Bangladesh and had continuously consumed arsenic-contaminated drinking water for at least 6 months. T2D cases were diagnosed using glucometer following the new diagnostic criteria (Fasting Blood Glucose > 126 mg/dl) from the WHO guideline (WHO 2006), or a self reported physician diagnosis of type 2 diabetes. Association between T2D and chronic arsenic exposure was estimated by multiple logistic regression with adjustment for age, sex, education, Body Mass Index (BMI) and family history of T2D. RESULTS: A total of 1004 individuals participated in the study. The prevalence of T2D was 9% (95% CI 7-11%). After adjustment for diabetes risk factors, an increased risk of type 2 diabetes was observed for arsenic exposure over 50 MUg/L with those in the highest category having almost double the risk of type 2 diabetes (OR=1.9 ; 95% CI 1.1-3.5). For most levels of arsenic exposure, the risk estimates are higher with longer exposure; a dose-response pattern was also observed. CONCLUSIONS: These findings suggest an association between chronic arsenic exposure through drinking water and T2D. Risks are generally higher with longer duration of arsenic exposure. The risk of T2D is highest among those who were exposed to the highest concentration of arsenic for more than 10 years. PMID- 22676250 TI - N-acetylcysteine prevents preterm birth by attenuating the LPS-induced expression of contractile associated proteins in an animal model. AB - OBJECTIVE: Intrauterine infection is associated with maternal immune activation (MIA) leading to preterm birth through upregulation of contractile associated proteins (CAPs). We hypothesized that N-acetylcysteine would decrease NF-kappaB activation and CAP expression in a MIA model for preterm birth. METHODS: Pregnant CD-1 mice were given intrauterine LPS or saline on day 15/20. They received NAC or saline prior to injection and were monitored until delivery. The rate of preterm birth in the control, LPS, and LPS + NAC animals was determined. In another group, animals were sacrificed 6 h after treatment and myometrium was collected. COX-2, connexin 43, and oxytocin receptor expression was determined. RESULTS: LPS administration resulted in preterm birth and this effect was attenuated by NAC. LPS increased COX-2, connexin 43, and oxytocin receptor expression. NAC significantly decreased COX-2 expression. LPS increased NF-kappaB activation; this was attenuated by NAC. CONCLUSION: NAC may be beneficial in prevention of MIA-related preterm birth through attenuation of NF-kappaB activation and COX-2 upregulation. PMID- 22676252 TI - The serum hepcidin:ferritin ratio is a potential biomarker for cirrhosis. AB - BACKGROUND: Serum hepcidin concentration is potentially affected by inflammation and iron stores in chronic liver disease (CLD), but little is known about the relationship between hepcidin and the degree of hepatic fibrosis. We investigated the potential role of serum hepcidin as a biomarker of advanced liver disease. METHODS: Serum hepcidin was measured in 332 adults with CLD of varying aetiologies, 45 healthy and 50 non-liver disease patient controls. Liver biopsy data were available for 228 CLD subjects. RESULTS: Hepcidin was decreased in CLD patients compared with non-liver disease patient controls (P < 0.0001) but not healthy controls, and was lowest in those with cirrhosis (P < 0.0001). Serum hepcidin correlated with hepatic hepcidin mRNA expression in 91 biopsy samples available for genetic analysis (r = 0.68, P < 0.0001). Hepcidin also correlated positively with serum ferritin concentration, transferrin saturation, ALT, serum albumin and haemoglobin, but negatively with serum bilirubin. The hepcidin:ferritin ratio was significantly lower in CLD subjects compared with healthy and disease controls, and decreased with each increase in the stage of fibrosis and siderosis. The hepcidin:ferritin ratio was associated with progressive fibrosis on linear regression, and a value of less than 0.1 was independently associated with cirrhosis on logistic regression analyses (OR 5.54, P < 0.001). Receiver operating characteristic analysis showed the hepcidin:ferritin ratio was able to distinguish between F0 and F4 stages of fibrosis (area under receiver operating characteristic curve = 0.86). CONCLUSIONS: The hepcidin:ferritin ratio is reduced in relation to increasing fibrosis in CLD and the use of this ratio may have potential future diagnostic implications as a marker of cirrhosis. PMID- 22676253 TI - Ionic liquid nanotribology: stiction suppression and surface induced shear thinning. AB - The friction and adhesion between pairs of materials (silica, alumina, and polytetrafluoroethylene) have been studied and interpreted in terms of the long ranged interactions present. In ambient laboratory air, the interactions are dominated by van der Waals attraction and strong adhesion leading to significant frictional forces. In the presence of the ionic liquid (IL) ethylammonium nitrate (EAN) the van der Waals interaction is suppressed and the attractive/adhesive interactions which lead to "stiction" are removed, resulting in an at least a 10 fold reduction in the friction force at large applied loads. The friction coefficient for each system was determined; coefficients obtained in air were significantly larger than those obtained in the presence of EAN (which ranged between 0.1 and 0.25), and variation in the friction coefficients between systems was correlated with changes in surface roughness. As the viscosity of ILs can be relatively high, which has implications for the lubricating properties, the hydrodynamic forces between the surfaces have therefore also been studied. The linear increase in repulsive force with speed, expected from hydrodynamic interactions, is clearly observed, and these forces further inhibit the potential for stiction. Remarkably, the viscosity extracted from the data is dramatically reduced compared to the bulk value, indicative of a surface ordering effect which significantly reduces viscous losses. PMID- 22676251 TI - Synthesis, structure, and metalation of two new highly porous zirconium metal organic frameworks. AB - Three new metal-organic frameworks [MOF-525, Zr(6)O(4)(OH)(4)(TCPP-H(2))(3); MOF 535, Zr(6)O(4)(OH)(4)(XF)(3); MOF-545, Zr(6)O(8)(H(2)O)(8)(TCPP-H(2))(2), where porphyrin H(4)-TCPP-H(2) = (C(48)H(24)O(8)N(4)) and cruciform H(4)-XF = (C(42)O(8)H(22))] based on two new topologies, ftw and csq, have been synthesized and structurally characterized. MOF-525 and -535 are composed of Zr(6)O(4)(OH)(4) cuboctahedral units linked by either porphyrin (MOF-525) or cruciform (MOF-535). Another zirconium-containing unit, Zr(6)O(8)(H(2)O)(8), is linked by porphyrin to give the MOF-545 structure. The structure of MOF-525 was obtained by analysis of powder X-ray diffraction data. The structures of MOF-535 and -545 were resolved from synchrotron single-crystal data. MOF-525, -535, and -545 have Brunauer Emmett-Teller surface areas of 2620, 1120, and 2260 m(2)/g, respectively. In addition to their large surface areas, both porphyrin-containing MOFs are exceptionally chemically stable, maintaining their structures under aqueous and organic conditions. MOF-525 and -545 were metalated with iron(III) and copper(II) to yield the metalated analogues without losing their high surface area and chemical stability. PMID- 22676256 TI - Weighted multiple testing procedures for genomic studies. AB - With the rapid development of biological technology, measurement of thousands of genes or SNPs can be carried out simultaneously. Improved procedures for multiple hypothesis testing when the number of tests is very large are critical for interpreting genomic data. In this paper, we review recent developments on three distinct but closely related methods involving p-value weighting to improve statistical power while also controlling for the false discovery rate or the family wise error rate. PMID- 22676255 TI - JAK-STAT and AKT pathway-coupled genes in erythroid progenitor cells through ontogeny. AB - BACKGROUND: It has been reported that the phosphatidylinositol 3-kinase (PI3K) AKT signaling pathway regulates erythropoietin (EPO)-induced survival, proliferation, and maturation of early erythroid progenitors. Erythroid cell proliferation and survival have also been related to activation of the JAK-STAT pathway. The goal of this study was to observe the function of EPO activation of JAK-STAT and PI3K/AKT pathways in the development of erythroid progenitors from hematopoietic CD34+ progenitor cells, as well as to distinguish early EPO target genes in human erythroid progenitors during ontogeny. METHODS: Hematopoietic CD34+ progenitor cells, isolated from fetal and adult hematopoietic tissues, were differentiated into erythroid progenitor cells. We have used microarray analysis to examine JAK-STAT and PI3K/AKT related genes, as well as broad gene expression modulation in these human erythroid progenitor cells. RESULTS: In microarray studies, a total of 1755 genes were expressed in fetal liver, 3844 in cord blood, 1770 in adult bone marrow, and 1325 genes in peripheral blood-derived erythroid progenitor cells. The erythroid progenitor cells shared 1011 common genes. Using the Ingenuity Pathways Analysis software, we evaluated the network pathways of genes linked to hematological system development, cellular growth and proliferation. The KITLG, EPO, GATA1, PIM1 and STAT3 genes represent the major connection points in the hematological system development linked genes. Some JAK STAT signaling pathway-linked genes were steadily upregulated throughout ontogeny (PIM1, SOCS2, MYC, PTPN11), while others were downregulated (PTPN6, PIAS, SPRED2). In addition, some JAK-STAT pathway related genes are differentially expressed only in some stages of ontogeny (STATs, GRB2, CREBB). Beside the continuously upregulated (AKT1, PPP2CA, CHUK, NFKB1) and downregulated (FOXO1, PDPK1, PIK3CG) genes in the PI3K-AKT signaling pathway, we also observed intermittently regulated gene expression (NFKBIA, YWHAH). CONCLUSIONS: This broad overview of gene expression in erythropoiesis revealed transcription factors differentially expressed in some stages of ontogenesis. Finally, our results show that EPO-mediated proliferation and survival of erythroid progenitors occurs mainly through modulation of JAK-STAT pathway associated STATs, GRB2 and PIK3 genes, as well as AKT pathway-coupled NFKBIA and YWHAH genes. PMID- 22676254 TI - Language development in school-age girls with fragile X syndrome. AB - BACKGROUND: Girls with fragile X syndrome (FXS) have a wide range of cognitive and language abilities. The range of language outcomes experienced by girls with FXS, however, has been relatively unexplored. The purpose of this exploratory study was to examine receptive and expressive language, with a focus on vocabulary and syntax, in a group of school-age girls with FXS. METHOD: Twenty one girls with FXS aged 7-15 years participated in the study. The girls completed a receptive vocabulary test, non-verbal IQ test and an expressive language sample. RESULTS: The mean IQ for this group of girls was at the cut-off for intellectual disability. Vocabulary was an area of strength relative to non verbal cognition. Age and non-verbal IQ were significant predictors of vocabulary performance. CONCLUSIONS: The data suggest that a substantial portion of the sample would qualify for speech and language services. This study highlights the need for continued research in the area of language and cognitive development in girls with the full mutation of fragile X. PMID- 22676257 TI - Effect of preparation conditions on the size and encapsulation properties of mPEG PLGA nanoparticles simultaneously loaded with vincristine sulfate and curcumin. AB - This study prepared monomethoxy poly(ethylene glycol)-poly(lactide-co-glycolide) (mPEG-PLGA) nanoparticles simultaneously loaded with vincristine sulfate (Vin) and curcumin (Cur) via O/W emulsion solvent evaporation. Five independent processing parameters were systematically evaluated to enhance the entrapment of dual agents with different properties (i.e. Vin and Cur, which are the hydrophilic and hydrophobic, respectively) into mPEG-PLGA nanoparticles and to control the particle size. The approaches used to investigate the enhancement of drug entrapment efficiencies and control over the particle size included mPEG PLGA concentration, polyvinyl alcohol (PVA) concentration, initial Vin/Cur content, dichloromethane-to-acetone volume ratio, and aqueous-to-organic phase volume ratio. The nanoparticles produced using the optimum formulation conditions had a particle size of 131.5 nm with a low polydispersity index of 0.047. The entrapment efficiencies were 63.52 +/- 2.36% for Vin and 54.60 +/- 2.46% for Cur (n = 3). The drug loadings were 1.06 +/- 0.04% for Vin and 3.64 +/- 0.16% for Cur (n = 3). PMID- 22676258 TI - Rh-catalyzed intermolecular reactions of cyclic alpha-diazocarbonyl compounds with selectivity over tertiary C-H bond migration. AB - Intermolecular Rh-catalyzed reactions of cyclic alpha-diazocarbonyl compounds with chemoselectivity over beta-hydride elimination are described. These methods represent the first general intermolecular reactions of Rh-carbenoids that are selective over tertiary beta-C-H bond migration. Successful transformations include cyclopropanation, cyclopropenation, and various X-H insertion reactions with a broad scope of substrates. We propose that the intermolecular approach of substrates to carbenes from acyclic diazo precursors may be relatively slow due to a steric interaction with the ester function, which is perpendicular to the pi system of the carbene. For carbenes derived from five- and six-membered cyclic alpha-diazocarbonyls, it is proposed that the carbene is constrained to be more conjugated with the carbonyl, thereby relieving the steric interaction for intermolecular reactions, and accelerating the rate of intermolecular reactivity relative to intramolecular beta-hydride migration. However, attempts to use alpha diazo-beta-ethylcaprolactone in intermolecular cyclopropanation with styrene were unsuccessful. It is proposed that the conformational flexibility of the seven membered ring allows the carbonyl to be oriented perpendicular to Rh-carbene. The significant intermolecular interaction between the carbonyl and approaching substrate is in agreement with the poor ability of alpha-diazo-beta ethylcaprolactone to participate in intermolecular cyclopropanation reactions. DFT calculations provide support for the mechanistic proposals that are described. PMID- 22676260 TI - Work-related empowerment of nurse managers: a systematic review. AB - The present study discusses how nurse managers' work-related empowerment has been investigated, in order to determine the level and relationships of empowerment among them. A systematic review was carried out, and a literature search was conducted with certain electronic databases for the period 1990-2009, using the main key words in various combinations. Only nine empirical studies in English were selected for review, in accordance with the requirements for the methodological quality and inclusion criteria. The most common type of study design was a descriptive survey (n = 5), and included various questionnaires, scales, and interviews. Nurse managers' structural, psychological, and work empowerment was found to be high or moderately high. The empowerment of nurse managers correlated positively with job satisfaction, perceived organizational support, role satisfaction, and managerial self-efficacy, and correlated negatively with emotional exhaustion and own health outcomes. Different theoretical approaches ensure a clear understanding of empowerment, but difficulties arise when the findings are synthesized across studies and settings because of the different theoretical frameworks used to conceptualize empowerment. PMID- 22676261 TI - Pharmacotherapy for adolescent alcohol use disorder. AB - Alcohol use disorder (AUD) occurs in few young adolescents, but is as common as in adults by the late teens. To address problems with the current American Psychiatric Association DSM-IV criteria, the anticipated DSM-V will eliminate the distinction between substance abuse and dependence in favour of a single category. For adolescents, pharmacotherapy for AUD may target alcohol withdrawal symptoms, alcohol consumption reinforcement properties, craving or co-morbid mental disorders. While uncommon among adolescents, severe alcohol withdrawal may require the closely monitored application of benzodiazepines. Disulfiram alters alcohol metabolism and has been shown to increase abstinence in adolescents with AUD, but sufficient motivation to maintain abstinence is needed for this approach to be appropriate. Medications to reduce alcohol craving, including naltrexone and acamprosate, may also assist some adolescents in maintaining abstinence. Adolescents with AUD typically also have co-morbid mental disorders and problems with other substances. Co-morbid mental disorders, such as major depressive disorder and attention-deficit hyperactivity disorder, may be addressed by pharmacotherapy. The potential for interactions between prescribed medications and alcohol or illicit substances necessitates patient education and monitoring. While there is a paucity of empirical information on the applicability of these pharmacotherapy approaches in adolescents, cautious application of these medications in selected cases in the context of systematic psychosocial interventions is warranted to promote abstinence and address associated problems. PMID- 22676263 TI - Erratum. PMID- 22676262 TI - Pathophysiology of acute pancreatitis: potential application from experimental models and human medicine to dogs. AB - The cellular events leading to pancreatitis have been studied extensively in experimental models. Understanding the cellular events and inciting causes of the multisystem inflammatory cascades that are activated with this disease is of vital importance to advance diagnosis and treatment of this condition. Unfortunately, the pathophysiology of pancreatitis in dogs is not well understood, and extrapolation from experimental and human medicine is necessary. The interplay of the inflammatory cascades (kinin, complement, cytokine) is extremely complex in both initiating leukocyte migration and perpetuating disease. Recently, nitric oxide (NO) and altered microcirculation of the pancreas have been proposed as major initiators of inflammation. In addition, the role of the gut is becoming increasingly explored as a cause of oxidative stress and potentiation of systemic inflammation in pancreatitis. PMID- 22676267 TI - Assessment of adherence to the CONSORT statement for quality of reports on randomized controlled trial abstracts from four high-impact general medical journals. AB - BACKGROUND: The extended Consolidated Standards of Reporting Trials (CONSORT) Statement for Abstracts was developed to improve the quality of reports of randomized controlled trials (RCTs) because readers often base their assessment of a trial solely on the abstract. To date, few data exist regarding whether it has achieved this goal. We evaluated the extent of adherence to the CONSORT for Abstract statement for quality of reports on RCT abstracts by four high-impact general medical journals. METHODS: A descriptive analysis of published RCT abstracts in The New England Journal of Medicine (NEJM), The Lancet, The Journal of American Medical Association (JAMA), and the British Medical Journal (BMJ) in the year 2010 was conducted by two reviewers, independently extracting data from a MEDLINE/PubMed search. RESULTS: We identified 271 potential RCT abstracts meeting our inclusion criteria. More than half of the abstracts identified the study as randomized in the title (58.7%; 159/271), reported the specific objective/hypothesis (72.7%; 197/271), described participant eligibility criteria with settings for data collection (60.9%; 165/271), detailed the interventions for both groups (90.8%; 246/271), and clearly defined the primary outcome (94.8%; 257/271). However, the methodological quality domains were inadequately reported: allocation concealment (11.8%; 32/271) and details of blinding (21.0%; 57/271). Reporting the primary outcome results for each group was done in 84.1% (228/271). Almost all of the abstracts reported trial registration (99.3%; 269/271), whereas reports of funding and of harm or side effects from the interventions were found in only 47.6% (129/271) and 42.8% (116/271) of the abstracts, respectively. CONCLUSIONS: These findings show inconsistencies and non-adherence to the CONSORT for abstract guidelines, especially in the methodological quality domains. Improvements in the quality of RCT reports can be expected by adhering to existing standards and guidelines as expressed by the CONSORT group. PMID- 22676259 TI - Common brain activations for painful and non-painful aversive stimuli. AB - BACKGROUND: Identification of potentially harmful stimuli is necessary for the well-being and self-preservation of all organisms. However, the neural substrates involved in the processing of aversive stimuli are not well understood. For instance, painful and non-painful aversive stimuli are largely thought to activate different neural networks. However, it is presently unclear whether there is a common aversion-related network of brain regions responsible for the basic processing of aversive stimuli. To help clarify this issue, this report used a cross-species translational approach in humans (i.e. meta-analysis) and rodents (i.e. systematic review of functional neuroanatomy). RESULTS: Animal and human data combined to show a core aversion-related network, consisting of similar cortical (i.e. MCC, PCC, AI, DMPFC, RTG, SMA, VLOFC; see results section or abbreviation section for full names) and subcortical (i.e. Amyg, BNST, DS, Hab, Hipp/Parahipp, Hyp, NAc, NTS, PAG, PBN, raphe, septal nuclei, Thal, LC, midbrain) regions. In addition, a number of regions appeared to be more involved in pain-related (e.g. sensory cortex) or non-pain-related (e.g. amygdala) aversive processing. CONCLUSIONS: This investigation suggests that aversive processing, at the most basic level, relies on similar neural substrates, and that differential responses may be due, in part, to the recruitment of additional structures as well as the spatio-temporal dynamic activity of the network. This network perspective may provide a clearer understanding of why components of this circuit appear dysfunctional in some psychiatric and pain-related disorders. PMID- 22676268 TI - Phosphatidylcholine formation by LPCAT1 is regulated by Ca(2+) and the redox status of the cell. AB - BACKGROUND: Unsaturated fatty acids are susceptible to oxidation and damaged chains are removed from glycerophospholipids by phospholipase A(2). De-acylated lipids are then re-acylated by lysophospholipid acyltransferase enzymes such as LPCAT1 which catalyses the formation of phosphatidylcholine (PC) from lysoPC and long-chain acyl-CoA. RESULTS: Activity of LPCAT1 is inhibited by Ca(2+), and a Ca(2+)-binding motif of the EF-hand type, EFh-1, was identified in the carboxyl terminal domain of the protein. The residues Asp-392 and Glu-403 define the loop of the hairpin structure formed by EFh-1. Substitution of D(392) and E(403) to alanine rendered an enzyme insensitive to Ca(2+), which established that Ca(2+) binding to that region negatively regulates the activity of the acyltransferase amino-terminal domain. Residue Cys-211 of the conserved motif III is not essential for catalysis and not sufficient for sensitivity to treatment by sulfhydryl-modifier agents. Among the several active cysteine-substitution mutants of LPCAT1 generated, we identified one to be resistant to treatment by sulfhydryl-alkylating and sulfhydryl-oxidizer agents. CONCLUSION: Mutant forms of LPCAT1 that are not inhibited by Ca(2+) and sulfhydryl-alkylating and -oxidizing agents will provide a better understanding of the physiological function of a mechanism that places the formation of PC, and the disposal of the bioactive species lysoPC, under the control of the redox status and Ca(2+) concentration of the cell. PMID- 22676269 TI - Antiausterity agents from Uvaria dac and their preferential cytotoxic activity against human pancreatic cancer cell lines in a nutrient-deprived condition. AB - Human pancreatic cancer cell lines are known for their inherent tolerance to nutrition starvation, which enables them to survive under a hypovascular (austerity) tumor microenvironment. The search for agents that preferentially retard the survival of cancer cells under low nutrition conditions (antiausterity agent) is a novel approach to anticancer drug discovery. In this study, it was found that a dichloromethane extract of the stem of Uvaria dac preferentially inhibited PANC-1 human pancreatic cancer cells survival under nutrition-deprived conditions at a concentration of 10 MUg/mL. Workup of this bioactive extract led to the discovery of (+)-grandifloracin (8) as a potent antiausterity agent as evaluated in a panel of four human pancreatic cancer cell lines, PANC-1 (PC(50), 14.5 MUM), PSN-1 (PC(50), 32.6 MUM), MIA PaCa-2 (PC(50), 17.5 MUM), and KLM-1 (32.7 MUM). (+)-Grandifloracin (8) has been isolated from a natural source for the first time. Its absolute stereochemistry was established by single-crystal X ray crystallography and circular dichroism spectroscopic analysis. In addition to this, seven other new highly oxygenated cyclohexene derivatives, named uvaridacanes A (1) and B (2), uvaridacols A-D (3, 4, 6, 7), and uvaridapoxide A (5), were also isolated and structurally characterized. PMID- 22676270 TI - Cancer-testis antigen BORIS is a novel prognostic marker for patients with esophageal cancer. AB - Esophageal squamous cell cancer (ESCC) is one of the most common lethal tumors in the world, and development of new diagnostic and therapeutic methods is needed. In this study, cancer-testis antigen, BORIS, was isolated by functional cDNA expression cloning using screening technique with serum IgG Abs from ESCC patients. BORIS was previously reported to show cancer-testis antigen like expression, but its immunogenicity has remained unclear in cancer patients. BORIS was considered to be an immunogenic antigen capable of inducing IgG Abs in patients with various cancers, including four of 11 ESCC patients. Immunohistochemical study showed that the BORIS protein was expressed in 28 of 50 (56%) ESCC tissues. The BORIS expression was significantly associated with lymph node metastasis in ESCC patients with pT1 disease (P = 0.036). Furthermore, the patients with BORIS-positive tumors had a poor overall survival (5-year survival rate: BORIS-negative 70.0% vs BORIS-positive 29.9%, log-rank P = 0.028) in Kaplan Meier survival analysis and log-rank test. Multivariate Cox proportional hazard model demonstrated that BORIS expression was an independent poor prognostic factor (hazard ratio = 4.158 [95% confidence interval 1.494-11.57], P = 0.006). Downregulation of BORIS with specific siRNAs resulted in decreased cell proliferation and invasion ability of ESCC cell lines. BORIS may be a useful biomarker for prognostic diagnosis of ESCC patients and a potential target for treatment including by BORIS-specific immunotherapy and molecular target therapy. PMID- 22676271 TI - A deep-blue emitter with electron transporting property to improve charge balance for organic light-emitting device. AB - Highly efficient deep-blue organic light-emitting devices (OLEDs) have been fabricated using 2,7-di(2,2':6',2"-terpyridin-4-yl)-9,9-dioctyl-9H-fluorene (DTPF) as the emitter, which has a wide energy gap, high emission quantum yield (Phif = 0.88), and high electron transporting property to improve the charge balance. A high efficiency of 2.55 cd/A and 2.67 lm/W are obtained in OLED. The device also exhibits a low turn-on voltage of 3.0 V and Commission Internationale de l'Eclairage (CIE) coordinates of (0.16, 0.09). PMID- 22676272 TI - Integrative study of pandemic A/H1N1 influenza infections: design and methods of the CoPanFlu-France cohort. AB - BACKGROUND: The risk of influenza infection depends on biological characteristics, individual or collective behaviors and the environmental context. The Cohorts for Pandemic Influenza (CoPanFlu) France study was set up in 2009 after the identification of the novel swine-origin A/H1N1 pandemic influenza virus. This cohort of 601 households (1450 subjects) representative for the general population aims at using an integrative approach to study the risk and characteristics of influenza infection as a complex combination of data collected from questionnaires regarding sociodemographic, medical, behavioral characteristics of subjects and indoor environment, using biological samples or environmental databases. METHODS/DESIGN: Households were included between December 2009 and July 2010. The design of this study relies on systematic follow up visits between influenza seasons and additional visits during influenza seasons, when an influenza-like illness is detected in a household via an active surveillance system. During systematic visits, a nurse collects individual and environmental data on questionnaires and obtains blood samples from all members of the household. When an influenza-like-illness is detected, a nurse visits the household three times during the 12 following days, and collects data on questionnaires regarding exposure and symptoms, and biological samples (including nasal swabs) from all subjects in the household. The end of the follow-up period is expected in fall 2012. DISCUSSION: The large amount of data collected throughout the follow-up will permit a multidisciplinary study of influenza infections. Additional data is being collected and analyzed in this ongoing cohort. The longitudinal analysis of these households will permit integrative analyses of complex phenomena such as individual, collective and environmental risk factors of infection, routes of transmission, or determinants of the immune response to infection or vaccination. PMID- 22676273 TI - Removal from the plasma of the free and esterified forms of cholesterol and transfer of lipids to HDL in type 2 diabetes mellitus patients. AB - BACKGROUND: The aim was to investigate new markers for type 2 diabetes (T2DM) dyslipidemia related with LDL and HDL metabolism. Removal from plasma of free and esterified cholesterol transported in LDL and the transfer of lipids to HDL are important aspects of the lipoprotein intravascular metabolism. The plasma kinetics (fractional clearance rate, FCR) and transfers of lipids to HDL were explored in T2DM patients and controls, using as tool a nanoemulsion that mimics LDL lipid structure (LDE). RESULTS: 14C- cholesteryl ester FCR of the nanoemulsion was greater in T2DM than in controls (0.07 +/- 0.02 vs. 0.05 +/- 0.01 h-1, p = 0.02) indicating that LDE was removed faster, but FCR 3 H- cholesterol was equal in both groups. Esterification rates of LDE free cholesterol were equal. Cholesteryl ester and triglyceride transfer from LDE to HDL was greater in T2DM (4.2 +/- 0.8 vs. 3.5 +/- 0.7%, p = 0.03 and 6.8 +/- 1.6% vs. 5.0 +/- 1.1, p = 0.03, respectively). Phospholipid and free cholesterol transfers were not different. CONCLUSIONS: The kinetics of free and esterified cholesterol tended to be independent in T2DM patients and the lipid transfers to HDL were also disturbed. These novel findings may be related with pathophysiological mechanisms of diabetic macrovascular disease. PMID- 22676274 TI - Spanish version of the Sleep Self-Report (SSR): factorial structure and psychometric properties. AB - BACKGROUND: The Sleep Self-Report (SSR) is a questionnaire initially created for use with a sample from the USA to assess sleep patterns and problems in school aged children. The objective of this study was to validate the SSR among a Spanish sample. METHODS: Participants were 1228 Spanish children from 8 to 12 years of age who completed the questionnaires at school anonymously. RESULTS: Internal consistency was good (omega = 0.85). Convergent validity with anxiety (r = 0.54) and perceived welfare (r = -0.53) measures, and divergent validity with a measure of academic performance and positive influence of peers (r = -0.22) were acceptable. Exploratory analysis suggested a factorial structure composed by four subscales: sleep quality, sleep anxiety, bedtime refusal and sleep routines. Confirmatory analysis indicated a good fit for the model (RMSEA = 0.04; GFI = 0.95; AGFI = 0.93; chi(2)/gl = 2.48). CONCLUSIONS: The SSR has demonstrated to have good psychometric properties in the Spanish-speaking sample of children. The factorial structure supported by exploratory and confirmatory analysis examines the most relevant areas of sleep in children. The satisfactory psychometric properties support the use of the Spanish version of the SSR by researchers and clinicians. PMID- 22676275 TI - Scrutinizing low-spin Cr(II) complexes. AB - The oxidation state of the chromium center in the following compounds has been probed using a combination of chromium K-edge X-ray absorption spectroscopy and density functional theory: [Cr(phen)(3)][PF(6)](2) (1), [Cr(phen)(3)][PF(6)](3) (2), [CrCl(2)((t)bpy)(2)] (3), [CrCl(2)(bpy)(2)]Cl(0.38)[PF(6)](0.62) (4), [Cr(TPP)(py)(2)] (5), [Cr((t)BuNC)(6)][PF(6)](2) (6), [CrCl(2)(dmpe)(2)] (7), and [Cr(Cp)(2)] (8), where phen is 1,10-phenanthroline, (t)bpy is 4,4'-di-tert-butyl 2,2'-bipyridine, and TPP(2-) is doubly deprotonated 5,10,15,20 tetraphenylporphyrin. The X-ray crystal structures of complexes 1, [Cr(phen)(3)][OTf](2) (1'), and 3 are reported. The X-ray absorption and computational data reveal that complexes 1-5 all contain a central Cr(III) ion (S(Cr) = (3)/(2)), whereas complexes 6-8 contain a central low-spin (S = 1) Cr(II) ion. Therefore, the electronic structures of 1-8 are best described as [Cr(III)(phen(*))(phen(0))(2)][PF(6)](2), [Cr(III)(phen(0))(3)][PF(6)](3), [Cr(III)Cl(2)((t)bpy(*))((t)bpy(0))], [Cr(III)Cl(2)(bpy(0))(2)]Cl(0.38)[PF(6)](0.62), [Cr(III)(TPP(3*-))(py)(2)], [Cr(II)((t)BuNC)(6)][PF(6)](2), [Cr(II)Cl(2)(dmpe)(2)], and [Cr(II)(Cp)(2)], respectively, where (L(0)) and (L(*))(-) (L = phen, (t)bpy, or bpy) are the diamagnetic neutral and one-electron-reduced radical monoanionic forms of L, and TPP(3*-) is the one-electron-reduced doublet form of diamagnetic TPP(2-). Following our previous results that have shown [Cr((t)bpy)(3)](2+) and [Cr(tpy)(2)](2+) (tpy = 2,2':6',2"-terpyridine) to contain a central Cr(III) ion, the current results further refine the scope of compounds that may be described as low-spin Cr(II) and reveal that this is a very rare oxidation state accessible only with ligands in the strong-field extreme of the spectrochemical series. PMID- 22676277 TI - Vascular associated gene variants in patients with preeclampsia: results from the Danish National Birth Cohort. AB - OBJECTIVE: Preeclampsia has been linked to subsequent vascular disease with many shared predisposing factors. We investigated the association between severe preeclampsia, and its subtypes, and specific vascular-related polymorphisms. DESIGN: The study was a retrospective nested case-cohort design. SETTING: Pregnant Danish women participating in the Danish National Birth Cohort. Population. 263 cases of severe preeclampsia and 1851 random controls were selected from the Danish National Birth Cohort. METHODS: We validated all cases of severe preeclampsia and genotyped for 108 single nucleotide polymorphisms (SNPs) that were selected based on previous publications on the association with vascular disease. Logistic models were used for statistical analyses. MAIN OUTCOME MEASURES: Maternal polymorphisms in genomic models. RESULTS: We found 17 of 108 SNPs associated with severe preeclampsia (p < 0.05). Women homozygous for the rs1799983 in NOS3 were 1.6-fold [95% confidence interval (CI) 1.0-2.4] more likely to develop severe preeclampsia. Women homozygous for the rs1010 SNP in VAMP8 were twofold (95%CI 1.1-3.5) more likely to deliver preterm when preeclampsia was present. Women homozygous for the rs10811661 SNP were 2.1-fold (95%CI 1.1-3.9) more likely to develop severe preeclampsia and 3.7-fold (95%CI 1.1-12.4) more likely to deliver a small-for-gestational age child when preeclampsia was present. All associations are available as Supporting Information. CONCLUSION: We found several vascular-associated SNPs linked to severe preeclampsia; however, most of these associations are probably by pure chance, which warrants replication and further translational research. To date, no specific SNP has yet proven valuable in a clinical setting in predicting preeclampsia. PMID- 22676276 TI - Protective effects of hyperbaric oxygen and iloprost on ischemia/reperfusion induced lung injury in a rabbit model. AB - BACKGROUND: The role of multiorgan damage in the mortality caused by ischemic limb injury is still not clarified. The objective of this study was to examine the potential protective effects of hyperbaric oxygen (HBO) and iloprost (IL) therapy on lung damage induced by limb ischemia/reperfusion injury in a rabbit model, using both biochemical and histopathological aspects. METHODS: Forty New Zealand white rabbits were randomly allocated into one of five study groups: HBO group (single session of HBO treatment); IL group (25 ng/kg/min infusion of IL); HBO + IL group (both HBO and IL); Control group (0.9% saline only); and a sham group. Acute hind limb ischemia-reperfusion was established by clamping the abdominal aorta for 1 h. HBO treatment and IL infusion were administrated during 60 min of ischemia and 60 min of reperfusion period. Blood pH, partial pressure of oxygen, partial pressure of carbon dioxide and levels of bicarbonate, sodium, potassium, creatine kinase, lactate dehydrogenase, and tumor necrosis factor alpha were determined at the end of the reperfusion period. Malondialdehyde was measured in the plasma and lung as an indicator of free radicals. After sacrifice, left lungs were removed and histopathological examination determined the degree of lung injury. RESULTS: In the control group, blood partial pressure of oxygen and bicarbonate levels were significantly lower and creatine kinase, lactate dehydrogenase, malondialdehyde and tumor necrosis factor-alpha levels were significantly higher than those of the HBO group, IL group, HBO + IL group and sham group. Similarly, the malondialdehyde levels in the lung tissue and plasma levels were significantly lower in the treatment groups compared with the control group. The extent of lung injury according to the histological findings was significantly higher in the control group. CONCLUSIONS: These results suggest that both HBO and IL therapies and their combination might be effectively used in the prevention of lung injury after ischemia/reperfusion injury of the lower extremities. PMID- 22676278 TI - Standardisation of digital human models. AB - Digital human models (DHM) have evolved as useful tools for ergonomic workplace design and product development, and found in various industries and education. DHM systems which dominate the market were developed for specific purposes and differ significantly, which is not only reflected in non-compatible results of DHM simulations, but also provoking misunderstanding of how DHM simulations relate to real world problems. While DHM developers are restricted by uncertainty about the user need and lack of model data related standards, users are confined to one specific product and cannot exchange results, or upgrade to another DHM system, as their previous results would be rendered worthless. Furthermore, origin and validity of anthropometric and biomechanical data is not transparent to the user. The lack of standardisation in DHM systems has become a major roadblock in further system development, affecting all stakeholders in the DHM industry. Evidently, a framework for standardising digital human models is necessary to overcome current obstructions. Practitioner Summary: This short communication addresses a standardisation issue for digital human models, which has been addressed at the International Ergonomics Association Technical Committee for Human Simulation and Virtual Environments. It is the outcome of a workshop at the DHM 2011 symposium in Lyon, which concluded steps towards DHM standardisation that need to be taken. PMID- 22676280 TI - The Road to RECOVERy: Hats off to the REassessment Campaign On VEterinary Resuscitation (RECOVER). PMID- 22676281 TI - RECOVER evidence and knowledge gap analysis on veterinary CPR. Part 7: Clinical guidelines. AB - OBJECTIVE: To present a series of evidence-based, consensus guidelines for veterinary CPR in dogs and cats. DESIGN: Standardized, systematic evaluation of the literature, categorization of relevant articles according to level of evidence and quality, and development of consensus on conclusions for application of the concepts to clinical practice. Questions in five domains were examined: Preparedness and Prevention, Basic Life Support, Advanced Life Support, Monitoring, and Post-Cardiac Arrest Care. Standardized worksheet templates were used for each question, and the results reviewed by the domain members, by the RECOVER committee, and opened for comments by veterinary professionals for 4 weeks. Clinical guidelines were devised from these findings and again reviewed and commented on by the different entities within RECOVER as well as by veterinary professionals. SETTING: Academia, referral practice and general practice. RESULTS: A total of 74 worksheets were prepared to evaluate questions across the five domains. A series of 101 individual clinical guidelines were generated. In addition, a CPR algorithm, resuscitation drug-dosing scheme, and postcardiac arrest care algorithm were developed. CONCLUSIONS: Although many knowledge gaps were identified, specific clinical guidelines for small animal veterinary CPR were generated from this evidence-based process. Future work is needed to objectively evaluate the effects of these new clinical guidelines on CPR outcome, and to address the knowledge gaps identified through this process. PMID- 22676282 TI - RECOVER evidence and knowledge gap analysis on veterinary CPR. Part 2: Preparedness and prevention. AB - OBJECTIVE: To systematically examine the evidence on the effect of prevention and preparedness measures on outcomes in veterinary cardiopulmonary resuscitation and to determine knowledge gaps. DESIGN: Standardized, systematic evaluation of the literature, categorization of relevant articles according to level of evidence and quality, and development of consensus on conclusions for application of the concepts to clinical practice. Relevant questions were answered on a worksheet template and reviewed by the Reassessment Campaign on Veterinary Resuscitation (RECOVER) prevention and preparedness domain members, by the RECOVER committee, and opened for comments by veterinary professionals for 3 months. SETTING: Academia, referral practice, and general practice. RESULTS: Nine worksheets were prepared to determine the extent to which preparation of the environment (charts, visual aids, etc) and personnel (training, debriefing, etc) are beneficial in improving return of spontaneous circulation. CONCLUSIONS: Of the questions evaluated, only the association between anesthesia-related cardiopulmonary arrest and better outcomes was supported by strong evidence. There is some evidence from the human literature that the use of cognitive aids, standardized didactic, and hands-on training with high-fidelity simulators, team and leadership training, and post-cardiac arrest debriefing improve adherence to cardiopulmonary resuscitation guidelines and, in some cases, patient outcomes. Veterinary studies investigating these issues are lacking, and development of initial guidelines is a crucial first step. PMID- 22676284 TI - Synergy at work: the RECOVER story. PMID- 22676283 TI - RECOVER evidence and knowledge gap analysis on veterinary CPR. Part 3: Basic life support. AB - OBJECTIVE: To systematically examine the evidence on basic life support (BLS) in veterinary CPR and to determine knowledge gaps. DESIGN: Standardized, systematic evaluation of the literature, categorization of relevant articles according to level of evidence and quality, and development of consensus on conclusions for application of the concepts to clinical practice. Relevant questions were answered on a worksheet template and reviewed by the Reassessment Campaign on Veterinary Resuscitation (RECOVER) BLS domain members, by the RECOVER committee and opened for comments by veterinary professionals for 30 days. SETTING: Academia, referral practice, and general practice. RESULTS: Sixteen worksheets were prepared to evaluate techniques for chest compression and ventilation strategies as well as identification of cardiopulmonary arrest (CPA). Major recommendations arising from this evidence review include performing chest compressions at a rate of at least 100/min at a compression depth of one-third to half the width of the chest with minimal pauses, and early instigation of ventilation at a rate of 8-10 breaths/min in intubated patients, or using a 30:2 compression/ventilation ratio in nonintubated patients. CONCLUSIONS: Although veterinary clinical trials are lacking, much of the experimental literature on BLS utilized canine models. The major conclusions from this analysis of the literature are the importance of early identification of CPA, and immediate initiation of BLS in these patients. Many knowledge gaps exist, most importantly in our understanding of the optimal hand placement and technique for chest compressions, warranting coordinated future studies targeted at questions of relevance to differences between veterinary species and humans. PMID- 22676285 TI - RECOVER evidence and knowledge gap analysis on veterinary CPR. Part 1: Evidence analysis and consensus process: collaborative path toward small animal CPR guidelines. AB - OBJECTIVE: To describe the methodology used by the Reassessment Campaign on Veterinary Resuscitation (RECOVER) to evaluate the scientific evidence relevant to small animal CPR and to compose consensus-based clinical CPR guidelines for dogs and cats. DESIGN: This report is part of a series of 7 articles on the RECOVER evidence and knowledge gap analysis and consensus-based small animal CPR guidelines. It describes the organizational structure of RECOVER, the evaluation process employed, consisting of standardized literature searches, the analysis of relevant articles according to study design, species and predefined quality markers, and the drafting of clinical CPR guidelines based on these data. Therefore, this article serves as the methodology section for the subsequent 6 RECOVER articles. SETTING: Academia, referral practice. RESULTS: RECOVER is a collaborative initiative that systematically evaluated the evidence on 74 topics relevant to small animal CPR and generated 101 clinical CPR guidelines from this analysis. All primary contributors were veterinary specialists, approximately evenly split between academic institutions and private referral practices. The evidence evaluation and guideline drafting processes were conducted according to a predefined sequence of steps designed to reduce bias and increase the repeatability of the findings, including multiple levels of review, culminating in a consensus process. Many knowledge gaps were identified that will allow prioritization of research efforts in veterinary CPR. CONCLUSIONS: Collaborative systematic evidence review is organizationally challenging but feasible and effective in veterinary medicine. More experience is needed to refine the process. PMID- 22676286 TI - RECOVER evidence and knowledge gap analysis on veterinary CPR. Part 4: Advanced life support. AB - OBJECTIVE: To systematically evaluate the evidence of the effect of advanced life support techniques on outcome in veterinary cardiopulmonary resuscitation (CPR) and to outline knowledge gaps. DESIGN: Standardized, systematic evaluation of the literature, categorization of relevant articles according to level of evidence and quality, and development of consensus on conclusions for application of the concepts to clinical practice. SETTING: Academia, referral practice, and general practice RESULTS: Sixteen population, intervention, control group, outcome questions were evaluated to determine if recommendations could be made concerning drug therapy, including vasopressors, vagolytics, corticosteroids, reversal agents, buffer therapy, and correction of electrolyte disturbances. Electrical defibrillation strategies as well as other advanced interventions such as open chest CPR, impedance threshold devices, and special considerations regarding anesthesia-related cardiopulmonary arrest (CPA) were also investigated. CONCLUSIONS: There is strong evidence supporting the use of standard-dose (0.01 mg/kg) epinephrine in CPR, as well as early electrical defibrillation for animals experiencing CPA due to ventricular fibrillation or pulseless ventricular tachycardia, preferentially using a biphasic defibrillator. For CPA due to certain causes and with the availability of advanced postcardiac arrest support, open chest CPR is preferred. Many knowledge gaps regarding other pharmacologic and advanced therapies were identified, and further studies are recommended to better systematically address these questions. PMID- 22676287 TI - RECOVER evidence and knowledge gap analysis on veterinary CPR. Part 5: Monitoring. AB - OBJECTIVE: To systematically examine the evidence on patient monitoring before, during, and following veterinary CPR and to identify scientific knowledge gaps. DESIGN: Standardized, systematic evaluation of the literature, categorization of relevant articles according to level of evidence and quality, and development of consensus on conclusions for application of the concepts to clinical practice. Relevant questions were answered on a worksheet template and reviewed by the Reassessment Campaign on Veterinary Resuscitation (RECOVER) monitoring domain members, by the RECOVER committee and opened for comments by veterinary professionals for 3 months. SETTING: Academia, referral practice, and general practice. RESULTS: Eighteen worksheets evaluated monitoring practices relevant for diagnosing cardiopulmonary arrest (CPA), monitoring CPR efforts, identifying return of spontaneous circulation (ROSC), and post-ROSC monitoring. CONCLUSIONS: Although veterinary clinical trials are lacking, experimental literature using canine models and human clinical trials provided relevant data. The major conclusions from this analysis of the literature highlight the utility of end tidal carbon dioxide (EtCO(2)) monitoring to identify ROSC and possibly to evaluate quality of CPR. In addition, recommendations for ECG analysis during CPR were addressed. Unless the patient is instrumented at the time of CPA, other monitoring devices (eg, Doppler flow probe) are likely not useful for diagnosis of CPA, and the possibility of pulseless electrical activity makes ECG inappropriate as a sole diagnostic tool. Optimal monitoring of the intra- and postcardiac arrest patient remains to be determined in clinical veterinary medicine, and further evaluation of the prognostic and prescriptive utility of EtCO(2) monitoring will provide material for future studies in veterinary CPR. PMID- 22676288 TI - RECOVER evidence and knowledge gap analysis on veterinary CPR. Part 6: Post cardiac arrest care. AB - OBJECTIVE: To systematically examine the evidence for interventions after the return of spontaneous circulation (ROSC) on outcomes from veterinary cardiopulmonary resuscitation and to determine important knowledge gaps. DESIGN: Standardized, systematic evaluation of the literature, categorization of relevant articles according to level of evidence and quality, and development of consensus on conclusions for application of the concepts to clinical post-cardiac arrest care. SETTING: Academia, referral practice, and general practice. RESULTS: Fifteen standardized clinical questions important for post-cardiac arrest care were asked and research articles relevant to answering these questions were identified through structured, explicit literature database searches. The majority of these articles report research in species other than dogs or cats or consisted of experimental work in canine cardiac arrest models. Outcome metrics reported in these studies widely varied and ranged from quantification of mechanistic endpoints, such as elaboration of reactive oxygen species, to survival, and functional neurologic outcome. CONCLUSIONS: Despite the near complete absence of clinical veterinary studies, the process allowed the formulation of statements for several postcardiac arrest treatments that were either supportive, such as mild therapeutic hypothermia or controlled reoxygenation, or neutral, such as for mannitol administration or seizure prophylaxis. Evidence grading allowed transparency in regards to the strength of these recommendations. Moreover, numerous knowledge gaps emerged that will allow generation of a road map for progress in veterinary post-cardiac arrest care. PMID- 22676289 TI - Formation of N2O from a nickel nitrosyl: isolation of the cis-[N2O2]2- intermediate. AB - Addition of 2,2'-bipyridine (bipy) to [Ni(NO)(bipy)][PF(6)] (1) results in formation of a rare five-coordinate nickel nitrosyl [Ni(NO)(bipy)(2)][PF(6)] (2). This complex exhibits a bent NO(-) ligand in the solid state. On standing in acetonitrile, 2 furnishes the NO coupled product, [Ni(kappa(2)-O(2)N(2))(bipy)] (8) in moderate yield. Subsequent addition of 2 equiv of acetylacetone (H(acac)) to 8 results in formation of [Ni(acac)(2)(bipy)], N(2)O, and H(2)O. Preliminary mechanistic studies suggest that the N-N bond is formed via a bimetallic coupling reaction of two NO(-) ligands. PMID- 22676290 TI - Tuning smart microgel swelling and responsive behavior through strong and weak polyelectrolyte pair assembly. AB - The layer-by-layer (LbL) assembly of polyelectrolyte pairs on temperature and pH sensitive cross-linked poly(N-isopropylacrylamide)-co-(methacrylic acid), poly(NIPAAm-co-MAA), microgels enabled a fine-tuning of the gel swelling and responsive behavior according to the mobility of the assembled polyelectrolyte (PE) pair and the composition of the outermost layer. Microbeads with well defined morphology were initially prepared by synthesis in supercritical carbon dioxide. Upon LbL assembly of polyelectrolytes, interactions between the multilayers and the soft porous microgel led to differences in swelling and thermoresponsive behavior. For the weak PE pairs, namely poly(L-lysine)/poly(L glutamic acid) and poly(allylamine hydrochloride)/poly(acrylic acid), polycation terminated microgels were less swollen and more thermoresponsive than native microgel, whereas polyanion-terminated microgels were more swollen and not significantly responsive to temperature, in a quasi-reversible process with consecutive PE assembly. For the strong PE pair, poly(diallyldimethylammonium chloride)/poly(sodium styrene sulfonate), the differences among polycation and polyanion-terminated microgels are not sustained after the first PE bilayer due to extensive ionic cross-linking between the polyelectrolytes. The tendencies across the explored systems became less noteworthy in solutions with larger ionic strength due to overall charge shielding of the polyelectrolytes and microgel. ATR FT-IR studies correlated the swelling and responsive behavior after LbL assembly on the microgels with the extent of H-bonding and alternating charge distribution within the gel. Thus, the proposed LbL strategy may be a simple and flexible way to engineer smart microgels in terms of size, surface chemistry, overall charge and permeability. PMID- 22676291 TI - Preparation and characterization of silk fibroin as a biomaterial with potential for drug delivery. AB - BACKGROUND: Degummed silk fibroin from Bombyx mori (silkworm) has potential carrier capabilities for drug delivery in humans; however, the processing methods have yet to be comparatively analyzed to determine the differential effects on the silk protein properties, including crystalline structure and activity. METHODS: In this study, we treated degummed silk with four kinds of calcium alcohol solutions, and performed secondary structure measurements and enzyme activity test to distinguish the differences between the regenerated fibroins and degummed silk fibroin. RESULTS: Gel electrophoresis analysis revealed that Ca(NO3)2-methanol, Ca(NO3)2-ethanol, or CaCl2-methanol treatments produced more lower molecular weights of silk fibroin than CaCl2-ethanol. X-ray diffraction and Fourier-transform infrared spectroscopy showed that CaCl2-ethanol produced a crystalline structure with more silk I (alpha-form, type II beta-turn), while the other treatments produced more silk II (beta-form, anti-parallel beta-pleated sheet). Solid-State 13C cross polarization and magic angle spinning-nuclear magnetic resonance measurements suggested that regenerated fibroins from CaCl2 ethanol were nearly identical to degummed silk fibroin, while the other treatments produced fibroins with significantly different chemical shifts. Finally, enzyme activity test indicated that silk fibroins from CaCl2-ethanol had higher activity when linked to a known chemotherapeutic drug, L-asparaginase, than the fibroins from other treatments. CONCLUSIONS: Collectively, these results suggest that the CaCl2-ethanol processing method produces silk fibroin with biomaterial properties that are appropriate for drug delivery. PMID- 22676293 TI - Factors influencing fecundity in experimental crosses of water lotus (Nelumbo nucifera Gaertn.) cultivars. AB - BACKGROUND: Breeding programs for the water lotus (Nelumbo nucifera) are hampered by an inability to account for variation in seed set associated with crosses between different cultivars. We studied seed set in two reciprocal crosses between lotus cultivars ('Guili' * 'Aijiangnan' and 'Molingqiuse' * 'Qinhuaiyanzhi') to obtain insights into factors that govern fecundity in these experimental hybrids. Pollen viability, stigma receptivity and embryo development were compared for each hybrid and reciprocal cross. RESULTS: Pollen viability of the individual cultivars ranged from 4.1% to 20.2%, with the highest level (>11.9%) for all cultivars observed from the earliest collected grains (05:00 06:00 a.m.). Stigmatic pollen germination peaked at 4 h after pollination and varied from 4.8 to 60.6 grains per stigma among the crosses. Production of normal embryos ranged from 7.6% to 58.8% at 1 d after pollination and from 0 to 25% by 11 d after pollination. Seed set in crosses (0.2-23.3%) was generally lower than in open-pollinated plants (8.4-26.5%). Similar to the germination results, seed set was substantially reduced in both reciprocal crosses. CONCLUSIONS: These results suggested that poor pollen fertility, low stigma receptivity, and embryo abortion were responsible for the failure of the crosses 'Molingqiuse' * 'Qinhuaiyanzhi', 'Qinhuaiyanzhi' * 'Molingqiuse', and 'Aijiangnan' * 'Guili'. PMID- 22676292 TI - The life cycle of Trypanosoma (Nannomonas) congolense in the tsetse fly. AB - BACKGROUND: The tsetse-transmitted African trypanosomes cause diseases of importance to the health of both humans and livestock. The life cycles of these trypanosomes in the fly were described in the last century, but comparatively few details are available for Trypanosoma (Nannomonas) congolense, despite the fact that it is probably the most prevalent and widespread pathogenic species for livestock in tropical Africa. When the fly takes up bloodstream form trypanosomes, the initial establishment of midgut infection and invasion of the proventriculus is much the same in T. congolense and T. brucei. However, the developmental pathways subsequently diverge, with production of infective metacyclics in the proboscis for T. congolense and in the salivary glands for T. brucei. Whereas events during migration from the proventriculus are understood for T. brucei, knowledge of the corresponding developmental pathway in T. congolense is rudimentary. The recent publication of the genome sequence makes it timely to re-investigate the life cycle of T. congolense. METHODS: Experimental tsetse flies were fed an initial bloodmeal containing T. congolense strain 1/148 and dissected 2 to 78 days later. Trypanosomes recovered from the midgut, proventriculus, proboscis and cibarium were fixed and stained for digital image analysis. Trypanosomes contained in spit samples from individually caged flies were analysed similarly. Mensural data from individual trypanosomes were subjected to principal components analysis. RESULTS: Flies were more susceptible to infection with T. congolense than T. brucei; a high proportion of flies infected with T. congolense established a midgut and subsequent proboscis infection, whereas many T. brucei infections were lost in the migration from foregut to salivary glands. In T. congolense, trypomastigotes ceased division in the proventriculus and became uniform in size. The trypanosomes retained trypomastigote morphology during migration via the foregut to the mouthparts and we confirmed that the trypomastigote-epimastigote transition occurred in the proboscis. We found no equivalent to the asymmetric division stage in T. brucei that mediates transition of proventricular trypomastigotes to epimastigotes. In T. congolense extremely long epimastigotes with remarkably elongated posterior ends were observed in both the proboscis and cibarium; no difference was found in the developmental stages in these two organs. Dividing trypomastigotes and epimastigotes were recovered from the proboscis, some of which were in transition from trypomastigote to epimastigote and vice versa. It remains uncertain whether these morphological transitions are mediated by cell division, since we also found non-dividing cells with a variously positioned, juxta-nuclear kinetoplast. CONCLUSIONS: We have presented a detailed description of the life cycle of T. congolense in its tsetse fly vector. During development in the fly T. congolense shares a common migratory pathway with its close relative T. brucei, culminating in the production of small metacyclic trypanosomes that can be inoculated with the saliva. Despite this outward similarity in life cycle, the transitional developmental stages in the foregut and mouthparts are remarkably different in the two trypanosome species. PMID- 22676294 TI - On the differential nature of induced and incidental echolalia in autism. AB - BACKGROUND: Echolalia is a verbal disorder, defined as 'a meaningless repetition of the words of others'. It is pathological, automatic and non-intentional behaviour, often observed in a variety of neurological and psychiatric disorders and above all in autism. We assume that echolalia is an imitative behaviour that is due to difficulties in inhibiting automatic repetition as seen in patients with frontal lobe damage. Our aim is to study the occurrence of echolalia under experimental conditions to investigate the nature of the phenomenon and its relationship with the severity of autism. METHODS: Eighteen participants with autism from 17 to 36 years old were recruited; they were administrated the Vineland scale, the Observational Rating Scale of Basic Functions and the Echolalia Questionnaire. In the Echolalia Questionnaire, questions were directly addressed to the autistic subject (induced procedure) or to the subject's caregiver while the subject was free to do what he wanted (incidental procedure). The data were analysed by multivariate regressions and Pearson's correlations. RESULTS: The results showed that echolalia occurred in both experimental situations; the mean value was significantly higher in the induced procedure, but results did not support the correlation with Vineland's score in the incidental procedure. It is likely that the two situations activated different processes. In particular, echolalia was statistically higher in the induced procedure as compared with the incidental one only for subjects with low score on Vineland, but in the incidental procedure, the presence of echolalia appeared to be uninfluenced by the functional capacity of subjects. CONCLUSIONS: The two experimental conditions require different monitoring systems to control this verbal behaviour. The echolalic phenomenon is an expression of dependence on the environment and may occur in a situation in which the autistic person is participating in a communicative act and, lacking inhibitory control, repeats the other's communication rather than selecting an answer. The deficit in inhibitory control in this situation does not seem to be present in subjects with higher efficiency. Incidental echolalia reflects the inability of the subject to filter out background environmental noise, which occasionally results in environmental dependency. PMID- 22676296 TI - Web tools for large-scale 3D biological images and atlases. AB - BACKGROUND: Large-scale volumetric biomedical image data of three or more dimensions are a significant challenge for distributed browsing and visualisation. Many images now exceed 10GB which for most users is too large to handle in terms of computer RAM and network bandwidth. This is aggravated when users need to access tens or hundreds of such images from an archive. Here we solve the problem for 2D section views through archive data delivering compressed tiled images enabling users to browse through very-large volume data in the context of a standard web-browser. The system provides an interactive visualisation for grey-level and colour 3D images including multiple image layers and spatial-data overlay. RESULTS: The standard Internet Imaging Protocol (IIP) has been extended to enable arbitrary 2D sectioning of 3D data as well a multi layered images and indexed overlays. The extended protocol is termed IIP3D and we have implemented a matching server to deliver the protocol and a series of Ajax/Javascript client codes that will run in an Internet browser. We have tested the server software on a low-cost linux-based server for image volumes up to 135GB and 64 simultaneous users. The section views are delivered with response times independent of scale and orientation. The exemplar client provided multi layer image views with user-controlled colour-filtering and overlays. CONCLUSIONS: Interactive browsing of arbitrary sections through large biomedical image volumes is made possible by use of an extended internet protocol and efficient server-based image tiling. The tools open the possibility of enabling fast access to large image archives without the requirement of whole image download and client computers with very large memory configurations. The system was demonstrated using a range of medical and biomedical image data extending up to 135GB for a single image volume. PMID- 22676295 TI - Demographic and clinical correlates of sexual dysfunction among Nigerian male outpatients on conventional antipsychotic medications. AB - BACKGROUND: In psychotic disorders, early intervention with antipsychotic medications increases the likelihood of favourable long-term course. However, the pharmacologic management especially with conventional antipsychotic medications is complicated by a high rate of adverse effects including sexual dysfunction. This study aims to determine the demographic and clinical factors associated with sexual dysfunction among male psychiatric outpatients on conventional antipsychotic medications in South-western Nigeria. METHODS: Two hundred and seventy five consecutive male outpatients with psychotic disorders on conventional antipsychotic medications were interviewed. Data was collected on demographic characteristics, illness-related and medication-related variables. Illness severity was assessed with the Brief psychiatric rating scale. The International Index of Erectile Function questionnaire was used to assess for sexual dysfunctions. RESULTS: A total of 111 (40.4%) respondents had one or more forms of sexual dysfunction. Sexual desire dysfunction was present in 47 (17.1%) of respondents, erectile dysfunction in 95 (34.5%), orgasmic dysfunctions in 51 (18.5%), intercourse dissatisfaction in 72 (26.2%) and overall dissatisfaction in 64 (23.3%). Sexual dysfunction was significantly associated with employment status, age, marital status, haloperidol use, medication dosage, and presence of psychopathology. Unemployment was the only significant independent correlate of sexual dysfunction, with unemployed respondents twice more likely to have sexual dysfunction compared with those employed (Wald = 3.865, Odds Ratio = 2.033, 95% confidence interval = 1.002 - 4.124, p = 0.049). CONCLUSIONS: The high prevalence of sexual dysfunction found in this study suggests a need among clinicians for increased awareness and recognition of the sexual side effects in patients taking conventional antipsychotic medications. This knowledge should guide conventional antipsychotic medication prescription in the at-risk population to improve treatment adherence. PMID- 22676297 TI - Recombinant human thyrotropin in veterinary medicine: current use and future perspectives. AB - Recombinant human thyrotropin (rhTSH) was developed after bovine thyrotropin (bTSH) was no longer commercially available. It was approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) as an aid to diagnostic follow-up of differentiated thyroid carcinoma in humans and for thyroid remnant ablation with radioiodine. In addition, rhTSH is used in human medicine to evaluate thyroid reserve capacity and to enhance radioiodine uptake in patients with metastatic thyroid cancer and multinodular goiter. Likewise, rhTSH has been used in veterinary medicine over the last decade. The most important veterinary use of rhTSH is thyroidal functional reserve testing for the diagnosis of canine hypothyroidism. Recent pilot studies performed at Ghent University in Belgium have investigated the use of rhTSH to optimize radioiodine treatment of canine thyroid carcinoma and feline hyperthyroidism. Radioiodine treatment optimization may allow a decreased therapeutic dosage of radioiodine and thus may improve radioprotection. This review outlines the current uses of rhTSH in human and veterinary medicine, emphasizing research performed in dogs and cats, as well as potential future applications. PMID- 22676298 TI - Enantiospecific perfluorooctane sulfonate (PFOS) analysis reveals evidence for the source contribution of PFOS-precursors to the Lake Ontario foodweb. AB - Exposure to perfluorooctane sulfonate (PFOS) may arise directly, from emission and exposure to PFOS itself, or indirectly via the environmental release and degradation of PFOS-precursors. Human serum enantiomer fractions (EFs) of 1m-PFOS have been shown to be nonracemic, suggesting that PFOS-precursors are a significant source of PFOS in humans, but little is known about the importance of PFOS-precursors in ecosystems. In the current work, concentrations of PFOS, perfluorooctane sulfonamide (PFOSA), PFOS isomer profiles, and EFs of 1m-PFOS were determined in Lake Ontario water, sediment, fishes and invertebrates. Concentrations of PFOS and PFOSA were highest in slimy sculpin and Diporeia, and concentrations of the two compounds were often correlated. 1m-PFOS was racemic in sediment, water, sculpin and rainbow smelt, but nonracemic in the top predator, lake trout, and all invertebrate species. Furthermore, EFs were correlated with the relative concentrations of PFOS and PFOSA in invertebrates. Overall, these empirical observations with a new analytical tool confirm previous suggestions that PFOS-precursors contribute to PFOS in the food web, likely via sediment. Implications are that future PFOS exposures in this ecosystem will be influenced by an in situ source, and that the apparent environmental behavior of PFOS (e.g., bioaccumulation potential) can be confounded by precursors. PMID- 22676299 TI - Diesel exhaust in miners study: how to understand the findings? AB - The Diesel Exhaust in Miners Study (DEMS) is an outstanding epidemiological project on the association between occupational diesel exhaust exposures, measured as long-term respirable elemental carbon (REC) estimates, and lung cancer mortality in a large cohort of US miners. Two articles published recently (Attfield et al. (J Natl Cancer Inst Epub, 2012), Silverman et al. (J Natl Cancer Inst Epub, 2012)) dsescribed the epidemiological findings. These papers are expected to have considerable impact on the evaluation of the carcinogenic potential of diesel exhaust and, furthermore, on occupational and environmental limit value discussions related to diesel motor emissions and particle exposures. DEMS found remarkable exposure-response relationships between REC exposure estimates and lung cancer mortality - conditional on a pronounced effect of surface vs. underground work on lung cancer risk. If this risk factor is ignored the estimated REC-lung cancer association is attenuated substantially. The authors relied on this risk factor in their main analyses. However, this factor "surface/underground work" remained unexplained. The factor lead the authors to introduce unusual cross-product terms of location and smoking in adjustment procedures and even caused the authors to hypothesize that high REC exposures are protective against lung cancer excess risks due to smoking. To understand the reliability of these conclusions, we should ask basic questions about the data collection process in DEMS: Did the mortality follow-up procedures suffer from errors like those that affected the NCI formaldehyde cohort study? Are the REC and/or smoking data reliable, and are these data collected/constructed in such a way that the procedures allow valid comparisons between surface and underground workers? Without clarifying the issues raised in this Commentary the Diesel Exhaust in Miners Study remains to be difficult to interpret. PMID- 22676300 TI - Effect of 5-[(125)I]iodo-2'-deoxyuridine uptake on the proliferation and pluripotency of human embryonic stem cells. AB - PURPOSE: Human embryonic stem cells (hESC) hold a great potential for regenerative medicine because, in principle, they can differentiate into any cell type found in the human body. In addition, studying the effect of ionizing radiation (IR) on hESC may provide valuable information about the response of human cells to IR exposure in their most naive state, as well as the consequences of IR exposure on the development of organisms. However, the effect of IR, in particular radionuclide uptake, on the pluripotency, proliferation and survival of hESC has not been extensively studied. METHODS: In this study we treated cultured hESC with 5-[(125)I]iodo-2'-deoxyuridine ((125)IdU), a precursor of DNA synthesis. Then we measured the expansion of colonies and expression of pluripotency markers in hESC. RESULTS: We found that uptake of (125)IdU was similar in both hESC and HT1080 human fibrosarcoma cells. However, treatment with 0.1 MUCi/ml (125)IdU for 24 hours resulted in complete death of the hESC population; whereas HT1080 cancer cells continued to grow. Treatment with a 10 fold lower dose (125)IdU (0.01 MUCi/ml) resulted in colonies of hESC becoming less defined with numerous cells growing in monolayer outside of the colonies showing signs of differentiation. Then we analyzed the expression of pluripotency markers (octamer-binding transcription factor 4 [Oct-4] and stage-specific embryonic antigen-4 [SSEA4]) in the surviving hESC. We found that hESC in the surviving colonies expressed pluripotency markers at levels comparable with those in the non-treated controls. CONCLUSIONS: Our results provide important initial insights into the sensitivity of hESC to IR, and especially that produced by the decay of an internalized radionuclide. PMID- 22676301 TI - Fundamentals of population pharmacokinetic modelling: modelling and software. AB - Population pharmacokinetic modelling is widely used within the field of clinical pharmacology as it helps to define the sources and correlates of pharmacokinetic variability in target patient populations and their impact upon drug disposition. This review focuses on the fundamentals of population pharmacokinetic modelling and provides an overview of the commonly available software programs that perform these functions. This review attempts to define the common, fundamental aspects of population pharmacokinetic modelling through a discussion of the literature describing the techniques and placing them in the appropriate context. An overview of the most commonly available software programs is also provided. Population pharmacokinetic modelling is a powerful approach where sources and correlates of pharmacokinetic variability can be identified in a target patient population receiving a pharmacological agent. There is a need to further standardize and establish the best approaches in modelling so that any model created can be systematically evaluated and the results relied upon. Various nonlinear mixed-effects modelling methods, packaged in a variety of software programs, are available today. When selecting population pharmacokinetic software programs, the consumer needs to consider several factors, including usability (e.g. user interface, native platform, price, input and output specificity, as well as intuitiveness), content (e.g. algorithms and data output) and support (e.g. technical and clinical). PMID- 22676302 TI - Absence of P300 reduction in South African treatment-naive adolescents with alcohol dependence. AB - BACKGROUND: Event-related potential studies show reduced P300 amplitudes in alcohol use disorders (AUDs). Alcohol exposure, genetic vulnerability to alcoholism, and comorbid psychopathology may contribute to this reduction. Most previous research has studied treated adult AUD samples, which have more severe alcoholism, a greater family history of AUDs, and more comorbidity than untreated samples. Untreated AUD samples tend to have little or no P300 amplitude reduction. We compared P300 between treatment-naive alcohol-dependent (TNAD) adolescents with no diagnosable substance abuse or psychiatric comorbidity and nonsubstance-abusing control (NSAC) adolescents. METHODS: Individuals between the ages of 13 and 18 years were recruited into either TNAD (n = 45) or NSAC (n = 64) groups. Alcohol use variables, family history density of alcohol problems, and psychiatric symptom counts were assessed in a clinician-administered evaluation. EEGs were recorded during performance of a 3-condition visual target detection task. RESULTS: P300 amplitudes were of comparable size in TNAD adolescents and NSAC adolescents. Boys demonstrated larger P3a and P3b amplitudes than girls. Within TNAD, P3b amplitude was reduced in those who drank more frequently, and P3a latency was more prolonged in subjects with higher internalizing symptom counts. CONCLUSIONS: The P300 deficit was not present in TNAD adolescents without comorbidities. In comparison to results of reduced P300 in treated adolescent AUD samples, this finding likely reflects moderate alcohol exposure, lower genetic vulnerability to alcoholism, and lack of comorbidity in our sample. Further work is needed to determine the relative contributions of these factors to changes in the P300. PMID- 22676303 TI - Fatty acids-stress attenuates gluconeogenesis induction and glucose production in primary hepatocytes. AB - BACKGROUND: Hepatic gluconeogenesis tightly controls blood glucose levels in healthy individuals, yet disorders of fatty acids (FAs) oxidation are characterized by hypoglycemia. We studied the ability of free-FAs to directly inhibit gluconeogenesis, as a novel mechanism that elucidates the hypoglycemic effect of FAs oxidation defects. METHODS: Primary rat hepatocytes were pre treated with FAs prior to gluconeogenic stimuli with glucagon or dexamethasone and cAMP. RESULTS: Pre-treatment with 1 mM FAs (mixture of 2:1 oleate:palmitate) for 1 hour prior to gluconeogenic induction, significantly decreases the induced expression of the gluconeogenic genes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6pase) as well as the induced glucose production by the cells. The inhibitory effect of FAs upon gluconeogenesis is abolished when pre-treatment is elongated to 18 hours, allowing clearance of FAs into triglycerides by the cells. Replacement of palmitate with the non-metabolic fatty acid 2-bromopalmitate inhibits esterification of FAs into triglycerides. Accordingly, the increased exposure to unesterified-FAs allows their inhibitory effect to be extended even when pre-treatment is elongated to 18 hours. Similar changes were caused by FAs to the induction of peroxisome-proliferator-activated receptor-gamma coactivator 1alpha (PGC1alpha) expression, indicating this transcriptional coactivator as the mediating link of the effect. This inhibitory effect of FAs upon gluconeogenic induction is shown to involve reduced activation of cAMP response element-binding (CREB) transcription factor. CONCLUSIONS: The present results demonstrate that free-FAs directly inhibit the induced gluconeogenic response in hepatocytes. Hence, high levels of free-FAs may attenuate hepatic gluconeogenesis, and liver glucose output. PMID- 22676304 TI - Ventilatory efficiency testing as prognostic value in patients with pulmonary hypertension. AB - BACKGROUND: Increased ventilatory response has been shown to have a high prognostic value in patients with chronic heart failure. Our aim was therefore to determine the ventilatory efficiency in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension by cardiopulmonary exercise testing (CPET) identifying PH-patients with increased risk for death within 24 months after evaluation. METHODS: 116 patients (age: 64 +/- 1 years) with a mean pulmonary arterial pressure of 35 +/- 1 mmHg underwent CPET and right heart catheterization. During a follow-up of 24 months, we compared the initial characteristics of survivors (n = 87) with nonsurvivors (n = 29). RESULTS: Significant differences (p <= 0.005) between survivors and nonsurvivors existed in ventilatory equivalents for oxygen (42.1 +/- 2.1 versus 56.9 +/- 2.6) and for carbon dioxide (Ve/VCO2) (47.5 +/- 2.2 versus 64.4 +/- 2.3). Patients with peak oxygen uptake <= 10.4 ml/min/kg had a 1.5-fold, Ve/VCO2 >= 55 a 7.8-fold, alveolar-arterial oxygen difference >= 55 mmHg a 2.9-fold, and with Ve/VCO2 slope >= 60 a 5.8-fold increased risk of mortality in the next 24 months. CONCLUSIONS: Our results demonstrate that abnormalities in exercise ventilation powerfully predict outcomes in PH. Consideration should be given to add clinical guidelines to reflect the prognostic importance of ventilatory efficiency parameters in addition to peak VO2. PMID- 22676305 TI - Chlorostannate(II) ionic liquids: speciation, Lewis acidity, and oxidative stability. AB - The anionic speciation of chlorostannate(II) ionic liquids, prepared by mixing 1 alkyl-3-methylimidazolium chloride and tin(II) chloride in various molar ratios, chi(SnCl2), was investigated in both solid and liquid states. The room temperature ionic liquids were investigated by (119)Sn NMR spectroscopy, X-ray photoelectron spectroscopy, and viscometry. Crystalline samples were studied using Raman spectroscopy, single-crystal X-ray crystallography, and differential scanning calorimetry. Both liquid and solid systems (crystallized from the melt) contained [SnCl(3)](-) in equilibrium with Cl(-) when chi(SnCl(2)) < 0.50, [SnCl(3)](-) in equilibrium with [Sn(2)Cl(5)](-) when chi(SnCl(2)) > 0.50, and only [SnCl(3)](-) when chi(SnCl(2)) = 0.50. Tin(II) chloride was found to precipitate when chi(SnCl(2)) > 0.63. No evidence was detected for the existence of [SnCl(4)](2-) across the entire range of chi(SnCl(2)), although such anions have been reported in the literature for chlorostannate(II) organic salts crystallized from organic solvents. Furthermore, the Lewis acidity of the chlorostannate(II)-based systems, expressed by their Gutmann acceptor number, has been determined as a function of the composition, chi(SnCl(2)), to reveal Lewis acidity for chi(SnCl(2)) > 0.50 samples comparable to the analogous systems based on zinc(II). A change of the Lewis basicity of the anion was estimated using (1)H NMR spectroscopy, by comparison of the measured chemical shifts of the C-2 hydrogen in the imidazolium ring. Finally, compositions containing free chloride anions (chi(SnCl(2)) < 0.50) were found to oxidize slowly in air to form a chlorostannate(IV) ionic liquid containing the [SnCl(6)](2-) anion. PMID- 22676306 TI - The interaction of canonical bone morphogenetic protein- and Wnt-signaling pathways may play an important role in regulating cartilage degradation in osteoarthritis. PMID- 22676307 TI - A four-part ecological model of community-focused therapeutic recreation and life skills services for children and youth with disabilities. AB - AIM: This article presents a four-part model of community-focused therapeutic recreation and life skills services for children's rehabilitation centres. METHOD AND RESULTS: The model is based on 15 years of clinical and management practice in a Canadian context combined with evidence from the literature on community focused service delivery. The model incorporates an ecological approach and principles from models of therapeutic recreation, community capacity building, and health promotion, as well as client/family-centred care. The four pillars of the model reflect a set of integrated services and principles designed to support the participation of children and youth with disabilities in community activities. The pillars involve providing community outreach services, providing community development services, sharing physical and educational resources with community partners, and promoting the organization as a community facility that provides adapted physical space and specialized instruction. The lessons learned in implementing the model are discussed, including the importance of ensuring the sustainability of community recreation programmes. CONCLUSIONS: The model will be of use to managers and service organizations seeking to develop an integrated programme of community-focused therapeutic recreation and life skills services based on a collaborative capacity-building approach. PMID- 22676308 TI - Enamel defects in permanent incisors after trauma to primary predecessors: inter observer agreement based on photographs. AB - Trauma to primary teeth may cause mineralization disturbances in the permanent successors. OBJECTIVE: To study the distribution and type of enamel defects in permanent incisors after trauma to primary teeth and to examine inter-observer agreement when registrations were based on photographs. MATERIAL AND METHODS: Of 266 children who suffered an oral injury to primary teeth in one county of Norway in 2003, 193 were included in a follow-up study to record enamel defects in the permanent successors 7 years later (age, 8-15 years). Clinical examination and intraoral photographs were undertaken by the principal investigator. The photographs were evaluated twice for enamel defects by three paediatric dentists. Evaluation 1: age at the time of injury, traumatized teeth and diagnoses were kept unknown to the examiners. Evaluation 2: age and trauma diagnoses were known to the examiners. Inter-observer agreement was calculated using Cohen's kappa and chi-square test. RESULTS: Of 338 successor teeth, 42% exhibited enamel defects. In neighbouring teeth (339) with non-injured predecessors, 30% were registered with defects. The most common enamel disturbance in successors was demarcated opacities, recorded in 18% of the teeth. Enamel defects owing to a previous trauma were registered in 37% of the children in Evaluation 1, kappa 0.88-0.93 and in 21% in Evaluation 2, kappa 0.63-0.84. The examiners disagreed on a higher proportion of the children when all information on the injury was available (P < 0.001). CONCLUSION: Demarcated enamel opacities were the most common defects in permanent successors. Although the inter-examiner agreement was good, the results indicated that recordings of enamel disturbances following trauma is associated with uncertainty. PMID- 22676309 TI - What are the potential outcomes of integrating emotionally competent behaviours into the care of psychiatric patients? AB - This descriptive study explored the concept of emotional competence in inpatient psychiatric nurse's daily interactions. Psychiatric registered nurses were asked to identify interactions of emotional competence they experienced on the nursing unit. Content analysis revealed deficits in self-awareness, mood management and managing relationships. PMID- 22676310 TI - Reduced graphene oxide/ZnO composite: reusable adsorbent for pollutant management. AB - Reduced graphene oxide (RGO) coated with ZnO nanoparticles (NPs) was synthesized by a self-assembly and in situ photoreduction method, and then their application for removing organic pollutant from water was investigated. The RGO@ZnO composite nanomaterial has unique structural features including well-dispersed NPs on the surface and dense NPs loading. This composite exhibited a greatly improved Rhodamine B (RhB) adsorption capacity and an improved photocatalytic activity for degrading RhB compared to neat ZnO NPs. These properties made RGO@ZnO reusable for pollutant adsorbent. The composite showed an excellent cycling performance for organic pollutant removal up to 99% recovery over several cycles via simulated sunlight irradiation. PMID- 22676311 TI - First report of Toxoplasma gondii infection in market-sold adult chickens, ducks and pigeons in northwest China. AB - BACKGROUND: Toxoplasma gondii infection is a global concern, affecting a wide range of warm-blooded animals and humans worldwide, including poultry. Domestic and companion birds are considered to play an important role in the transmission of T. gondii to humans and other animals. However, little information on T. gondii infection in domestic birds in Lanzhou, northwest China was available. Therefore, this study was performed to determine the seroprevalence of T. gondii infection in domestic birds in Lanzhou, northwest China. METHODS: In the present study, the seroprevalence of T. gondii antibodies in 413 (305 caged and 108 free range) adult chickens, 334 (111 caged and 223 free-range) adult ducks and 312 adult pigeons in Lanzhou, northwest China, were examined using the modified agglutination test (MAT). RESULTS: 30 (7.26%) chickens, 38 (11.38%) ducks and 37 (11.86%) pigeons were found to be positive for T. gondii antibodies at the cut off of 1:5. The prevalences in caged and free-range chickens were 6.23% and 10.19% respectively, however, statistical analysis showed that the difference was not significant (P > 0.05). The seroprevalences in caged and free-range ducks were 6.31% and 13.90% respectively, but the difference was not statistically significant (P > 0.05). CONCLUSIONS: The results of the present survey indicated the presence of T. gondii infection in adult chickens, ducks and pigeons sold for meat in poultry markets in Lanzhou, northwest China, which poses a potential risk for T. gondii infection in humans and other animals in this region. This is the first seroprevalence study of T. gondii infection in domestic birds in this region. PMID- 22676312 TI - Experimental climate change weakens the insurance effect of biodiversity. AB - Ecosystems are simultaneously affected by biodiversity loss and climate change, but we know little about how these factors interact. We predicted that climate warming and CO (2) -enrichment should strengthen trophic cascades by reducing the relative efficiency of predation-resistant herbivores, if herbivore consumption rate trades off with predation resistance. This weakens the insurance effect of herbivore diversity. We tested this prediction using experimental ocean warming and acidification in seagrass mesocosms. Meta-analyses of published experiments first indicated that consumption rate trades off with predation resistance. The experiment then showed that three common herbivores together controlled macroalgae and facilitated seagrass dominance, regardless of climate change. When the predation-vulnerable herbivore was excluded in normal conditions, the two resistant herbivores maintained top-down control. Under warming, however, increased algal growth outstripped control by herbivores and the system became algal-dominated. Consequently, climate change can reduce the relative efficiency of resistant herbivores and weaken the insurance effect of biodiversity. PMID- 22676313 TI - Interactions of an Arabidopsis RanBPM homologue with LisH-CTLH domain proteins revealed high conservation of CTLH complexes in eukaryotes. AB - BACKGROUND: RanBPM (Ran-binding protein in the microtubule-organizing centre) was originally reported as a centrosome-associated protein in human cells. However, RanBPM protein containing highly conserved SPRY, LisH, CTLH and CRA domains is currently considered as a scaffolding protein with multiple cellular functions. A plant homologue of RanBPM has not yet been characterized. RESULTS: Based on sequence similarity, we identified a homologue of the human RanBPM in Arabidopsis thaliana. AtRanBPM protein has highly conserved SPRY, LisH, CTLH and CRA domains. Cell fractionation showed that endogenous AtRanBPM or expressed GFP-AtRanBPM are mainly cytoplasmic proteins with only a minor portion detectable in microsomal fractions. AtRanBPM was identified predominantly in the form of soluble cytoplasmic complexes ~230-500 kDa in size. Immunopurification of AtRanBPM followed by mass spectrometric analysis identified proteins containing LisH and CRA domains; LisH, CRA, RING-U-box domains and a transducin/WD40 repeats in a complex with AtRanBPM. Homologues of identified proteins are known to be components of the C-terminal to the LisH motif (CTLH) complexes in humans and budding yeast. Microscopic analysis of GFP-AtRanBPM in vivo and immunofluorescence localization of endogenous AtRanBPM protein in cultured cells and seedlings of Arabidopsis showed mainly cytoplasmic and nuclear localization. Absence of colocalization with gamma-tubulin was consistent with the biochemical data and suggests another than a centrosomal role of the AtRanBPM protein. CONCLUSION: We showed that as yet uncharacterized Arabidopsis RanBPM protein physically interacts with LisH-CTLH domain-containing proteins. The newly identified high molecular weight cytoplasmic protein complexes of AtRanBPM showed homology with CTLH types of complexes described in mammals and budding yeast. Although the exact functions of the CTLH complexes in scaffolding of protein degradation, in protein interactions and in signalling from the periphery to the cell centre are not yet fully understood, structural conservation of the complexes across eukaryotes suggests their important biological role. PMID- 22676314 TI - Behaviour problems, maternal internalising symptoms and family relations in families of adolescents and adults with fragile X syndrome. AB - BACKGROUND: Studies have linked the behaviour problems of children with fragile X syndrome (FXS) to maternal well-being, but less is known about how behaviour problems relate to important family factors such as marital satisfaction and family cohesion. METHODS: Married mothers of 115 adolescents and adults with FXS completed questionnaires and interviews, and maternal CGG repeat length was obtained by medical/laboratory records or by blood analysis. RESULTS: Indirect effects were present between behaviour problems and family variables in that behaviour problems were positively related to maternal internalising symptoms which were, in turn, negatively associated with both family cohesion and marital satisfaction. Direct associations between behaviour problems and family relationship variables were not significant. CONCLUSIONS: Findings suggest the importance of intervening with behaviour problems in individuals with FXS and identify maternal mental health as a potentially powerful conduit for the effects of child behaviour on relationships within these families. Implications for targeted interventions are discussed. PMID- 22676315 TI - Nurse-perceived barriers to effective communication regarding prognosis and optimal end-of-life care for surgical ICU patients: a qualitative exploration. AB - BACKGROUND: Integration of palliative care for intensive care unit (ICU) patients is important but often challenging, especially in surgical ICUs (SICUs), in part because many surgeons equate palliative care with terminal care and failure of restorative care. SICU nurses, who are key front-line clinicians, can provide insights into barriers for delivery of optimal palliative care in their setting. METHODS: We developed a focus group guide to identify barriers to two key components of palliative care-optimal communication regarding prognosis and optimal end-of-life care-and used the tool to conduct focus groups of nurses providing bedside care in three SICUs at a tertiary care, academic, inner city hospital. Using content analysis technique, responses were organized into thematic domains that were validated by independent observers and a subset of participating nurses. RESULTS: Four focus groups included a total of 32 SICU nurses. They identified 34 barriers to optimal communication regarding prognosis, which were summarized into four domains: logistics, clinician discomfort with discussing prognosis, inadequate skill and training, and fear of conflict. For optimal end-of-life care, the groups identified 24 barriers in four domains: logistics, inability to acknowledge an end-of-life situation, inadequate skill and training, and cultural differences relating to end-of-life care. CONCLUSIONS: Nurses providing bedside care in SICUs identify barriers in several domains that may impede optimal discussions of prognoses and end-of-life care for patients with surgical critical illness. Consideration of these perceived barriers and the underlying SICU culture is relevant for designing interventions to improve palliative care in this setting. PMID- 22676316 TI - The Chinese medicine formula HB01 reduces choroidal neovascularization by regulating the expression of vascular endothelial growth factor. AB - BACKGROUND: Choroidal neovascularization (CNV) remains the leading cause of newly acquired blindness in the developed world. Currently anti-vascular endothelial growth factor (VEGF) therapies are broadly used to treat neovascular ocular disorders. Here we demonstrate the effect of a traditional Chinese medicine formula, HB01, on CNV. METHODS: A rat model of laser-induced CNV was used to investigate the effect of HB01 in vivo. The CNV lesions in the eye were evaluated using fundus fluorescein angiography and visualized/quantified using confocal microscopy. Expression of VEGF in the choroidal and retinal tissues was measured using quantitative real-time PCR and immunohistochemistry. RESULTS: We demonstrated that a traditional Chinese Medicine formula, named HB01, significantly reduced neovascularization in a rat CNV model. The effect of HB01 on CNV was comparable to the intravitreal injection of bevacizumab (Avastin). Our results also suggested that HB01 may reduce CNV partially through inhibiting the expression of VEGF. CONCLUSIONS: These data support HB01 as an alternative therapy for ocular neovascular disorders. PMID- 22676317 TI - Stochastic distribution of the required coefficient of friction for level walking -an in-depth study. AB - This study investigated the stochastic distribution of the required coefficient of friction (RCOF) which is a critical element for estimating slip probability. Fifty participants walked under four walking conditions. The results of the Kolmogorov-Smirnov two-sample test indicate that 76% of the RCOF data showed a difference in distribution between both feet for the same participant under each walking condition; the data from both feet were kept separate. The results of the Kolmogorov-Smirnov goodness-of-fit test indicate that most of the distribution of the RCOF appears to have a good match with the normal (85.5%), log-normal (84.5%) and Weibull distributions (81.5%). However, approximately 7.75% of the cases did not have a match with any of these distributions. It is reasonable to use the normal distribution for representation of the RCOF distribution due to its simplicity and familiarity, but each foot had a different distribution from the other foot in 76% of cases. PRACTITIONER SUMMARY: The stochastic distribution of the required coefficient of friction (RCOF) was investigated for use in a statistical model to improve the estimate of slip probability in risk assessment. The results indicate that 85.5% of the distribution of the RCOF appears to have a good match with the normal distribution. PMID- 22676318 TI - Cardiac autonomic function measured by heart rate variability and turbulence in pre-hypertensive subjects. AB - Non-dipping blood pressure pattern was shown to be associated with increased cardiovascular events. In addition, cardiac autonomic dysfunction was found to be associated with non-dipper phenomenon. In this study, we aimed to evaluate the cardiac autonomic functions in dipper and non-dipper pre-hypertensive subjects. A total of 65 pre-hypertensive subjects were enrolled in this study. They were divided into two groups as non-dippers (40 subjects, 52% female) and dippers (25 subjects, 52.5% female). Cardiac autonomic functions of the two groups were compared with the aid of heart rate variability, heart rate turbulence (HRT), atrial premature contractions (APCs), ventricular premature contractions (VPCs), and mean heart rate (MHR). There was no significant difference between non dippers and dippers in basal characteristics. The two parameters of HRT, turbulence onset and turbulence slope, were found to be significantly abnormal in non-dippers than in dippers (P < .011 and P < .002, respectively). Heart rate variability parameters, including SDNN, SDANN, RMSSD, and pNN50, were found to be similar in dipper and non-dipper pre-hypertensive subjects (P < .998, P < .453, P < .205, and P < .788, respectively). APCs, VPCs, and MHR were compared, and there were statistical differences between the groups (APCs 5.80 +/- 4.55, 9.14 +/- 7.33, P < .024; VPCs 8.48 +/- 8.83, 13.23 +/- 9.68, P < .044; and MHR 70.16 +/- 11.08, 76.26 +/- 11.31, P < .035; respectively). This study demonstrated a possible cardiac autonomic dysfunction in pre-hypertensive subjects with non dipper pattern. This may be a basis for future studies related to pre hypertension and non-dipping BP pattern. PMID- 22676319 TI - Pharmacologic interventions for hidradenitis suppurativa: what does the evidence say? AB - BACKGROUND: Hidradenitis suppurativa is a chronic debilitating skin disease that is recalcitrant to treatment. OBJECTIVE: The aim of this article was to conduct an evidence-based review of pharmacologic interventions for the treatment of hidradenitis suppurativa (HS). METHODS: A systematic search of MEDLINE, EMBASE, and the Cochrane database was conducted to identify controlled trials (randomized controlled trials, cohorts, and case-control studies) published in English. The abstracts were examined using predetermined inclusion and exclusion criteria. The identified studies were used to develop the recommendations. Clinically relevant outcomes that were assessed were: clinical remission, patient global assessment, physician global assessment, number of skin lesions, and improvement in Hurley's stage, or Sartorius score. RESULTS: Overall there was sparse evidence to support the use of any treatment modality. There is fair evidence to support the use of antibacterials in HS and they should be used as first-line therapy (level II 1/grade B). There is fair evidence to support the use of intravenous infliximab in the treatment of advanced HS (Hurley's stage II and III). Given the high cost of anti-tumor necrosis factor therapy and its adverse-effect profile, intravenous infliximab should be offered to patients with severe disease affecting their daily activities who have failed antibacterial therapy (level I/grade B). There is insufficient evidence to support the use of antiandrogens in HS; consideration could be given to their use in women with mild to moderate disease (Hurley's stage I and II) who have failed antibacterial therapy and women with an abnormal hormone profile (level II-2/grade I). CONCLUSIONS: The existing evidence suggests that antibacterials and anti-tumor necrosis factor therapy are effective in the treatment of HS. Further research is required to confirm the efficacy of the different medications within these groups and to explore the efficacy of other treatment modalities. PMID- 22676320 TI - Quartet decomposition server: a platform for analyzing phylogenetic trees. AB - BACKGROUND: The frequent exchange of genetic material among prokaryotes means that extracting a majority or plurality phylogenetic signal from many gene families, and the identification of gene families that are in significant conflict with the plurality signal is a frequent task in comparative genomics, and especially in phylogenomic analyses. Decomposition of gene trees into embedded quartets (unrooted trees each with four taxa) is a convenient and statistically powerful technique to address this challenging problem. This approach was shown to be useful in several studies of completely sequenced microbial genomes. RESULTS: We present here a web server that takes a collection of gene phylogenies, decomposes them into quartets, generates a Quartet Spectrum, and draws a split network. Users are also provided with various data download options for further analyses. Each gene phylogeny is to be represented by an assessment of phylogenetic information content, such as sets of trees reconstructed from bootstrap replicates or sampled from a posterior distribution. The Quartet Decomposition server is accessible at http://quartets.uga.edu. CONCLUSIONS: The Quartet Decomposition server presented here provides a convenient means to perform Quartet Decomposition analyses and will empower users to find statistically supported phylogenetic conflicts. PMID- 22676321 TI - Prophylactic antibiotic regimens in tumor surgery (PARITY) survey. AB - BACKGROUND: Deep infection following endoprosthetic limb reconstruction for sarcoma of the long bones is a devastating complication occurring in 15% of sarcoma patients. Optimizing infection protocols and conducting definitive surgical trials are critical to improving outcomes. In this study, the PARITY (Prophylactic Antibiotic Regimens in Tumor Surgery) investigators aimed to examine surgeon preferences in antibiotic prophylaxis and perceptions about current evidence, as well as to ascertain interest in resolving uncertainty in the evidence with clinical trials. METHODS: We used a cross-sectional survey to examine current practice in the prescription of prophylactic antibiotics in Musculoskeletal Tumor Surgery. The survey was approved by our institution's Ethics Board and emailed to all Active Members of the Musculoskeletal Tumor Society (MSTS) and Canadian Orthopaedic Oncology Society (CANOOS). Survey answers were collected using an anonymous online survey tool. RESULTS: Of the 96 surgeons who received the questionnaire, 72 responded (75% response rate (% CI: 65.5, 82.5%)). While almost all respondents agreed antibiotic regimens were important in reducing the risk of infection, respondents varied considerably in their choices of antibiotic regimens and dosages. Although 73% (95% CI: 61, 82%) of respondents prescribe a first generation cephalosporin, 25% favor additional coverage with an aminoglycoside and/or Vancomycin. Of those who prescribe a cephalosporin, 33% prescribe a dosage of one gram for all patients and the reminder prescribe up to 2 grams based on body weight. One in three surgeons (95% CI: 25, 48%) believes antibiotics could be discontinued after 24 hours but 40% (95% CI: 30, 53%) continue antibiotics until the suction drain is removed. Given the ongoing uncertainty in evidence to guide best practices, 90% (95% CI: 81, 95%) of respondents agreed that they would change their practice if a large randomized controlled trial showed clear benefit of an antibiotic drug regimen different from what they are currently using. Further support for a clinical trial was observed by an overwhelming surgeon interest (87%; 95% CI: 77, 93%) in participating in a multi-center randomized controlled study. CONCLUSION: The current lack of guidelines for the prescription of prophylactic antibiotics in Musculoskeletal Tumor Surgery has left Orthopaedic Oncologists with varying opinions and practices. The lack of current evidence and strong surgeon support for participating in a definitive study provides strong rationale for clinical trials. PMID- 22676323 TI - Crown reattachment with complicated chisel-type fracture using fiber-reinforced post. AB - INTRODUCTION: Maxillary incisors and specifically their crowns are the most common teeth involved in dental trauma because of their exposed position in the dental arch. Traumatized anterior teeth require quick functional and esthetic repair. In the case of a complex crown fracture, with the necessity of endodontic treatment, fiber-reinforced posts (FRC) were used to create a central support stump to restore the dental morphology. CASE REPORT: A 24-year-old male patient came to the dental clinic with dental injury to the maxillary left central incisor with a chisel-type fracture that extended subgingivally with a widely open pulp chamber. The patient reported a sports injury had occurred 1 day before. Provisional reposition of the crown was completed using a composite splint and after that endodontic treatment has been performed. Two days later, a fiber-reinforced composite resin post was placed into the canal and adhesive reattachment of the fragment also completed. The tooth was prepared for a composite resin veneer in the gingival third of the vestibular surface because of a visible fracture line. CONCLUSIONS: The combined use of a fiber-reinforced composite resin post and the original crown fragment is a simple and efficient procedure for the treatment of traumatized anterior teeth that appears to offer pleasing esthetic and functional results that is less invasive than conventional prosthodontic treatment. PMID- 22676322 TI - Ileocolic intussusception due to a cecal endometriosis: case report and review of literature. AB - Cecal endometriosis and ileocolic intussusception due to a cecal endometriosis is extremely rare. We report a case of a woman who presented an ileocecal intussusception due to a cecal endometriosis. The patient gave two months history of chronic periombilical pain requiring regular hospital admission and analgesia. The symptoms were not related to menses. A laparotomy was performed and revealed an ileocolic intussusception. The abdominal exploration did not find any endometriosis lesion. Ileocaecal resection was performed. Microscopic examination showed a cystic component, lined by a regular cylindric epithelium. Foci of endometrial tissue were observed in the cecal subserosa and muscularis mucosal, with irregular endometrial glands lined by cylindric epithelium without atypia immunostained with CK7, and characteristic endometrial stroma immunostained with CD10. Cecal endometriosis and ileocolic intussusception due to a cecal endometriosis is extremely rare. Diagnose of etiology remains challenging due to the absence of clinical and radiological specific characteristics. VIRTUAL SLIDE: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2975867306869166. PMID- 22676324 TI - Natural infection of Didelphis aurita (Mammalia: Marsupialia) with Leishmania infantum in Brazil. AB - BACKGROUND: The opossum Didelphis have been considered as natural hosts of Leishmania parasites in the New World, suggesting an important role in the epidemiology of Visceral Leishmaniasis (VL). Among six extant species that belong to the genus Didelphis, only two (D. marsupialis and D. albiventris), have been mentioned as natural hosts of Leishmania infantum in Brazil and Colombia. In the present paper, it is reported for the first time, the observation of intracellular parasites (amastigotes) in tissues of Didelphis aurita naturally infected with Leishmania infantum in Brazil. We also discuss some aspects associated to the relationship between L. infantum and the geographical distribution of some species of the genus Didelphis. METHODS: The opossums studied were caught by wire traps (Tomahawk) in Barra de Guaratiba, a peri-urban area in Rio de Janeiro. The opossums were killed with an overdose of Thiopental sodium.At necropsy, macroscopic alterations were examined and samples from liver, spleen, lymph nodes, ear, abdominal skin, scent glands and bone marrow were collected for parasitological and molecular diagnoses. RESULTS: Forty-eight opossums were captured in an AVL endemic region, 30 being caught in a mangrove area and eighteen animals in a forest area near to some residential-yards. Among the thirty opossums trapped in the mangrove area, all of them were negative by both imprint and sera samples assayed on Dipstick Tests, that is a test based on a combination of protein-A colloidal gold conjugate and rk39 Leishmania antigen to detect anti-Leishmania antibody in serum or plasma. At the macroscopic examination one out of eighteen opossums, caught close to the forest, presented alterations compatible with spleen hypertrophy and three were positive by Dipstick Tests (16.6%) and presented amastigotes in the spleen and in one of them, the parasites were also observed in a submandibular lymph node. Leishmania infantum infections were confirmed through dot blot hybridization using a L. infantum-specific biotinylated probe. CONCLUSIONS: In the present paper we present the first report of amastigotes in the tissues of Didelphis aurita (Mammalia: Marsupialia) naturally infected with Leishmania infantum. We also attempt to claim the particular role of some opossum species as hosts of Leishmania infantum, contributing at least in part on the description of potential sylvatic reservoirs. PMID- 22676325 TI - Adsorption of arsenic on polyaluminum granulate. AB - The kinetics and efficiencies of arsenite and arsenate removal from water were evaluated using polyaluminum granulates (PAG) with high content of aluminum nanoclusters. PAG was characterized to be meso- and macroporous, with a specific surface area of 35 +/- 1 m(2) g(-1). Adsorption experiments were conducted at pH 7.5 in deionized water and synthetic water with composition of As-contaminated groundwater in the Pannonian Basin. As(III) and As(V) sorption was best described by the Freundlich and Langmuir isotherm, respectively, with a maximum As(V) uptake capacity of ~200 MUmol g(-1) in synthetic water. While As(III) removal reached equilibrium within 40 h, As(V) was removed almost entirely within 20 h. Micro X-ray fluorescence and electron microscopy revealed that As(III) was distributed uniformly within the grain, whereas As(V) diffused up to 81 MUm into PAG. The results imply that As(V) is adsorbed 3 times faster while being transported 10(5) times slower than As(III) in Al hydroxide materials. PMID- 22676326 TI - BioWord: a sequence manipulation suite for Microsoft Word. AB - BACKGROUND: The ability to manipulate, edit and process DNA and protein sequences has rapidly become a necessary skill for practicing biologists across a wide swath of disciplines. In spite of this, most everyday sequence manipulation tools are distributed across several programs and web servers, sometimes requiring installation and typically involving frequent switching between applications. To address this problem, here we have developed BioWord, a macro-enabled self installing template for Microsoft Word documents that integrates an extensive suite of DNA and protein sequence manipulation tools. RESULTS: BioWord is distributed as a single macro-enabled template that self-installs with a single click. After installation, BioWord will open as a tab in the Office ribbon. Biologists can then easily manipulate DNA and protein sequences using a familiar interface and minimize the need to switch between applications. Beyond simple sequence manipulation, BioWord integrates functionality ranging from dyad search and consensus logos to motif discovery and pair-wise alignment. Written in Visual Basic for Applications (VBA) as an open source, object-oriented project, BioWord allows users with varying programming experience to expand and customize the program to better meet their own needs. CONCLUSIONS: BioWord integrates a powerful set of tools for biological sequence manipulation within a handy, user friendly tab in a widely used word processing software package. The use of a simple scripting language and an object-oriented scheme facilitates customization by users and provides a very accessible educational platform for introducing students to basic bioinformatics algorithms. PMID- 22676327 TI - Influence of colour on acquisition and generalisation of graphic symbols. AB - BACKGROUND: Children with autism may benefit from using graphic symbols for their communication, language and literacy development. The purpose of this study was to investigate the influence of colour versus grey-scale displays on the identification of graphic symbols using a computer-based intervention. METHOD: An alternating treatment design was employed to examine the learning and generalisation of 58 colour and grey-scale symbols by four preschool children with autism. The graphic symbols were taught via a meaning-based intervention using stories and educational games. RESULTS AND CONCLUSIONS: Results demonstrate that all of the children were able to learn and maintain symbol identification over time for both symbol displays with no apparent differences. Differences were apparent for two of the children who exhibited better generalisation when learning grey-scale symbols first. The other two showed no noticeable difference, between displays when generalising from one display to the other. Implications and further research are discussed. PMID- 22676329 TI - Predicting leisure participation of school-aged children with cerebral palsy: longitudinal evidence of child, family and environmental factors. AB - OBJECTIVE: This longitudinal study aims to determine which child, family and environmental variables measured at 2 years of age predict leisure participation in formal and informal activities in school aged children with cerebral palsy (CP). METHODS: Parents of 46 children with CP (mean age at baseline: 2 years 6 months, SD 0 years 1 month; at follow-up 6 years 7 months, SD 0 years 9 months; n = 26 boys, n = 20 girls; Gross Motor Classification System I = 30%, II = 7%, III = 28%, IV = 24%, V = 11%) completed the Children's Assessment of Participation and Enjoyment indicating their child's participation. Multivariate regression models were used to identify early predictors of participation. RESULTS: Movement ability was a significant child-related predictor for formal activities (R(2) 17%, P < 0.05). Movement ability and social skills were most predictive (R(2) 62%, P < 0.00) for informal activities. The feeling of being restricted in family participation was the single most predictive factor for formal and informal activities at family level (R(2) 12%, P < 0.05, R(2) 25%, P < 0.05). Type of daycare was the only environmental variable that was predictive, and only for informal activities (R(2) 16%, P < 0.05). In the overall model movement ability was most predictive for leisure participation in formal activities (R(2) 17%, P < 0.05). Movement ability and social skills are the most important predictors for informal leisure participation (R(2) 62%, P < 0.01). CONCLUSIONS: Several variables are found to be related to formal and informal participation at age 6. Movement ability and social skills at age 2 are most predictive of leisure participation when the child is 6 years old. PMID- 22676328 TI - Dietary whey protein lessens several risk factors for metabolic diseases: a review. AB - Obesity and type 2 diabetes mellitus (DM) have grown in prevalence around the world, and recently, related diseases have been considered epidemic. Given the high cost of treatment of obesity/DM-associated diseases, strategies such as dietary manipulation have been widely studied; among them, the whey protein diet has reached popularity because it has been suggested as a strategy for the prevention and treatment of obesity and DM in both humans and animals. Among its main actions, the following activities stand out: reduction of serum glucose in healthy individuals, impaired glucose tolerance in DM and obese patients; reduction in body weight; maintenance of muscle mass; increases in the release of anorectic hormones such as cholecystokinin, leptin, and glucagon like-peptide 1 (GLP-1); and a decrease in the orexigenic hormone ghrelin. Furthermore, studies have shown that whey protein can also lead to reductions in blood pressure, inflammation, and oxidative stress. PMID- 22676330 TI - Effectiveness of the frequency rhythmic electrical modulation system for the treatment of chronic and painful venous leg ulcers in older adults. AB - Frequency rhythmic electrical modulation system (FREMS) is an innovative type of transcutaneous electrotherapy used in a rehabilitation setting for the treatment of pain, especially in diabetic patients. In a randomized clinical trial, we tested the hypothesis that FREMS is effective in the treatment of chronic and painful venous leg ulcers in 20 older patients. Group A (10 patients) received FREMS and topical treatment, whereas group B (10 patients) received topical treatment alone. Over a period of 3 consecutive weeks, 15 treatment sessions were done for each group. Wound healing and tissue repair were evaluated with the Visitrack digital planimetry system and photos. Pain was evaluated using the Visual Analogic Scale (VAS). The measurements were done at baseline and after 5, 10, and 15 days of treatment, with follow-up measurements after 15 and 30 days from the last treatment session. Group A showed a statistically significant decrease in ulcer area during the treatment and follow-up. The VAS score showed a statistically significant decrease after 5 and 10 days of treatment. Group B showed a statistically decrease in ulcer area after 5, 10, and 15 days of treatment with a reduction of VAS score only at 15 days of follow-up. At the end of the treatment, the comparison of the change in ulcer area and the change in VAS score of each group showed a statistically significant difference between groups, suggesting the therapeutic and analgesic efficacy of FREMS in reducing pain and area of chronic venous leg ulcers in older adults. Further investigation is needed to determine its reproducibility in larger case series or randomized clinical trials with longer follow-up periods. PMID- 22676332 TI - Association of methylenetetrahydrofolate reductase gene 677C>T polymorphism with hypertension in older women in a population of Buenos Aires City. AB - We examined the relationship between the 677C >T polymorphism in the MTHFR gene and tHcy in normotensive (NT) and hypertensive (HT) subjects and the influence of sex and age in a cross-sectional study. Smoking habits, history of vascular disease, diabetes, and tHcy were significantly associated with T allele as hypertension risk factors. The T allele was significantly related with higher tHcy in (i) men versus women (P < .01), (ii) men and women older than 47 years versus the younger ones (P < .05 and P < .001, respectively), (iii) HT women versus NT women (P < .01), and (iv) older HT women versus older NT women (P < .01). We found an association between the 677C>T MTHFR polymorphism and tHcy with hypertension that in women is manifested with age. PMID- 22676333 TI - Ribozyme-mediated gene knock down strategy to dissect the consequences of PDGF stimulation in vascular smooth muscle cells. AB - BACKGROUND: Vascular Smooth Muscle Cells (VSMCs), due to their plasticity and ability to shift from a physiological contractile-quiescent phenotype to a pathological proliferating-activated status, play a central role in the onset and progression of atherosclerosis and cardiovascular diseases. PDGF-BB, among a series of cytokines and growth factors, has been identified as the critical factor in this phenotypic switch. In order to obtain new insights on the molecular effects triggered by PDGF-BB, a hammerhead ribozyme targeting the membrane receptor PDGFR-beta was applied to inhibit PDGF pathway in porcine VSMCs. FINDINGS: Ribozymes, loaded on a cationic polymer-based vehicle, were delivered into cultured VSMCs. A significant impairment of the activation mechanisms triggered by PDGF-BB was demonstrated since cell migration decreased after treatments. In order to functionally validate the effects of PDGFR-beta partial knock down we focused on the phosphorylation status of two proteins, protein disulfide isomerase-A3 (PDI-A3) and heat shock protein-60 (HSP-60), previously identified as indicative of VSMC phenotypic switch after PDGF-BB stimulation. Interestingly, while PDI-A3 phosphorylation was counteracted by the ribozyme administration indicating that PDI-A3 is a factor downstream the receptor signalling cascade, the HSP-60 phosphorylation status was greatly increased by the ribozyme administration. CONCLUSION: These contradictory observations suggested that PDGF-BB might trigger different parallel pathways that could be modulated by alternative isoforms of the receptors for the growth factor. In conclusion the knock down strategy here described enables to discriminate between two tightly intermingled pathways. Moreover it opens new attractive perspectives in functional investigations where combined gene knock down and proteomic technologies would allow the identification of key factors and pathways involved in VSMC-linked pathological disorders. PMID- 22676331 TI - Thromboxane inhibitors attenuate inflammatory and fibrotic changes in rat liver despite continued ethanol administrations. AB - BACKGROUND: Thromboxane levels are increased in rats fed ethanol (EtOH), whereas thromboxane inhibitors reduce alcoholic liver injury. The aim of this study is to determine whether thromboxane inhibitors could attenuate the already established alcoholic liver injury. METHODS: Rats were fed EtOH and liquid diet for 6 weeks by intragastric infusion to induce liver injury after which EtOH was continued for 2 more weeks, and the rats were treated with either a thromboxane synthase inhibitor (TXSI) or a thromboxane receptor antagonist (TXRA). Liver pathology, lipid peroxidation, nuclear factor-kappa-B (NF-kappaB) activity, tumor necrosis factor-alpha (TNF-alpha), cyclooxygenase-2 (COX-2), and transforming growth factor-beta1 (TGF-beta(1) ) were evaluated. RESULTS: Administration of fish oil and EtOH caused fatty liver, necrosis, inflammation and fibrosis accompanied by increased in lipid peroxidation, NF-kappaB activity, and expression of TNF-alpha, COX-2, and TGF-beta(1) . Treatment with the thromboxane inhibitors ameliorated a certain level of the pathological and biochemical abnormalities. In particular, TXSI in addition to reducing necrosis, inflammation and fibrosis also decrease the severity of fatty liver. CONCLUSIONS: Thromboxane inhibitors attenuated the alcoholic liver injury, inflammation and fibrotic changes despite continued EtOH administration. Inhibition of the production of thromboxane by thromboxane inhibitor and receptor antagonists may be a useful treatment strategy in clinical alcoholic liver disease. PMID- 22676334 TI - Synthesis and coordination chemistry of phosphine oxide decorated dibenzofuran platforms. AB - A four-step synthesis for 4,6-bis(diphenylphosphinoylmethyl)dibenzofuran (4) from dibenzofuran and a two-step synthesis for 4,6 bis(diphenylphosphinoyl)dibenzofuran (5) are reported along with coordination chemistry of 4 with In(III), La(III), Pr(III), Nd(III), Er(III), and Pu(IV) and of 5 with Er(III). Crystal structure determinations for the ligands, 4.CH(3)OH and 5, the 1:1 complexes [In(4)(NO(3))(3)], [Pr(4)(NO(3))(3)(CH(3)CN)].0.5CH(3)CN, [Er(4)(NO(3))(3)(CH(3)CN)].CH(3)CN, [Pu(4)Cl(4)].THF and the 2:1 complex [Nd(4)(2)(NO(3))(2)](2)(NO(3))(2).(H(2)O).4(CH(3)OH) are described. In these complexes, ligand 4 coordinates in a bidentate POP'O' mode via the two phosphine oxide O-atoms. The dibenzofuran ring O-atom points toward the central metal cations, but in every case it is more than 4 A from the metal. A similar bidentate POP'O' chelate structure is formed between 5 and Er(III) in the complex, {[Er(5)(2)(NO(3))(2)](NO(3)).4(CH(3)OH)}(0.5), although the nonbonded Er...O(furan) distance is reduced to ~3.6 A. The observed bidentate chelation modes for 4 and 5 are consistent with results from molecular mechanics computations. The solvent extraction performance of 4 and 5 in 1,2-dichloroethane for Eu(III) and Am(III) in nitric acid solutions is described and compared against the extraction behavior of n-octyl(phenyl)-N,N-diisobutylcarbamoylmethyl phosphine oxide (OPhiDiBCMPO) measured under identical conditions. PMID- 22676335 TI - Skilled interaction among professional carers in special accommodations for adult people with learning disabilities. AB - Communicative difficulties affect interactions between people with learning disabilities and their carers. Despite such difficulties, however, some carers seem to interact successfully with people who have limited ability to communicate verbally and exhibit challenging behaviour. This study aims to illuminate skilled interaction among carers working in special accommodations for people with learning disabilities. Interactions between 16 caregivers and 11 residents with learning disabilities were recorded on video. Verbal and non-verbal interaction skills among the carers were identified. Four caring situations with people with learning disabilities were chosen to illuminate skilled interaction. The transcribed text was subjected to qualitative content analysis and core stories were created. The results show that skilled interaction between the carers and the people with learning disabilities is based upon being confirming, sharing daily life experience, giving time and space, and using congruent and distinct language. In this paper we present examples that offer concrete suggestions of how to promote successful interaction and create meaning in the shared day-to-day life in special accommodations for people with learning disabilities. PMID- 22676336 TI - Testing the hypothesis that psychotic illness begins when subthreshold hallucinations combine with delusional ideation. AB - OBJECTIVE: While hallucinations and delusions are often considered as a single class of 'positive symptoms', little is known about their dynamic cooccurrence in relation to clinical outcome in non-help-seeking people. METHOD: The Netherlands Mental Health and Incidence Study (NEMESIS-1) is a longitudinal study of mental disorders (n = 7075) with three measurements over a 3-year period. Risk factors, persistence of psychotic experiences, and clinical outcome were analyzed for groups with: i) no psychotic experiences, ii) only delusions, iii) only hallucinations, and iv) both delusions and hallucinations. RESULTS: Hallucinations and delusions occurred together more often (T0, 3.5%; T1, 1.0%; T2, 0.9%) than that predicted by chance (T0, 1.0%; T1, 0.1%; T2, 0.04%). The group with both symptoms showed more 'first-rank'-like delusions compared with the group with only delusions. Having both hallucinations and delusions, compared to isolated symptoms, was associated more strongly with risk factors, comorbid affective symptoms, negative symptoms, and persistence of psychotic experiences. This was not an artifact of having more symptoms in general. CONCLUSION: Experiencing both delusions and hallucinations is an indicator of greater etiological load resulting in more clinical outcome. A specific 'hallucinatory delusional state' may represent an early phase of exacerbation of aberrant attribution of salience, increasing risk for clinical outcome. PMID- 22676338 TI - Common and rare plant species respond differently to fertilisation and competition, whether they are alien or native. AB - Plant traits associated with alien invasiveness may also distinguish rare from common native species. To test this, we grew 23 native (9 common, 14 rare) and 18 alien (8 common, 10 rare) herbaceous species in Switzerland from six plant families under nutrient-addition and competition treatments. Alien and common species achieved greater biomass than native and rare species did overall respectively. Across alien and native origins, common species increased total biomass more strongly in response to nutrient addition than rare species did and this difference was not confounded by habitat dissimilarities. There was a weak tendency for common species to survive competition better than rare species, which was also independent of origin. Overall, our study suggests that common alien and native plant species are not fundamentally different in their responses to nutrient addition and competition. PMID- 22676337 TI - A multi-institutional study evaluating the diagnostic utility of the spec cPLTM and SNAP(r) cPLTM in clinical acute pancreatitis in 84 dogs. AB - BACKGROUND: Pancreas-specific lipase is reported to aid in diagnosing acute pancreatitis (AP) in dogs but has not been rigorously evaluated clinically. HYPOTHESIS/OBJECTIVES: To describe variability of disease in dogs with suspected clinical AP, and to evaluate accuracy of 2 pancreatic-specific lipase immunoassays, Spec cPL (SPEC) and SNAP cPL (SNAP), in diagnosing clinical AP. We hypothesized that SPEC and SNAP provide better diagnostic accuracy than serum amylase or total lipase. ANIMALS: A total of 84 dogs; 27 without AP and 57 with clinical signs associated with AP. METHODS: Multicenter study. Dogs were prospectively enrolled based upon initial history and physical examination, then retrospectively classified into groups according to the likelihood of having clinical AP by a consensus of experts blinded to SPEC and SNAP results. Bayesian latent class analyses were used to estimate the diagnostic accuracy of SPEC and SNAP. RESULTS: The estimates for test sensitivities and specificities, respectively, ranged between 91.5-94.1% and 71.1-77.5% for SNAP, 86.5-93.6% and 66.3-77.0% for SPEC (cutoff value of 200 MUg/L), 71.7-77.8% and 80.5-88.0% for SPEC (cutoff value of 400 MUg/L), and were 52.4-56.0% and 76.7-80.6% for amylase, and 43.4-53.6% and 89.3-92.5% for lipase. CONCLUSIONS AND CLINICAL IMPORTANCE: SNAP and SPEC have higher sensitivity for diagnosing clinical AP than does measurement of serum amylase or lipase activity. A positive SPEC or SNAP has a good positive predictive value (PPV) in populations likely to have AP and a good negative predictive value (NPV) when there is low prevalence of disease. PMID- 22676339 TI - Establishment and characterization of a sustained delayed-type hypersensitivity model with arthritic manifestations in C57BL/6J mice. AB - INTRODUCTION: Rheumatoid arthritis (RA) is a chronic progressive, inflammatory and destructive autoimmune disease, characterised by synovial joint inflammation and bone erosion. To better understand the pathophysiology and underlying immune mechanisms of RA various models of arthritis have been developed in different inbred strains of mice. Establishment of arthritis models with components of adaptive immunity in the C57BL/6J strain of mice has been difficult, and since most genetically modified mice are commonly bred on this background, there is a need to explore new ways of obtaining robust models of arthritis in this strain. This study was undertaken to establish and characterise a novel murine model of arthritis, the delayed-type hypersensitivity (DTH)-arthritis model, and evaluate whether disease can be treated with compounds currently used in the treatment of RA. METHODS: DTH-arthritis was induced by eliciting a classical DTH reaction in one paw with methylated bovine serum albumin (mBSA), with the modification that a cocktail of type II collagen monoclonal antibodies was administered between the immunisation and challenge steps. Involved cell subsets and inflammatory mediators were analysed, and tissue sections evaluated histopathologically. Disease was treated prophylactically and therapeutically with compounds used in the treatment of RA. RESULTS: We demonstrate that DTH-arthritis could be induced in C57BL/6 mice with paw swelling lasting for at least 28 days and that disease induction was dependent on CD4+ cells. We show that macrophages and neutrophils were heavily involved in the observed pathology and that a clear profile of inflammatory mediators associated with these cell subsets was induced locally. In addition, inflammatory markers were observed systemically. Furthermore, we demonstrate that disease could be both prevented and treated. CONCLUSIONS: Our findings indicate that DTH-arthritis shares features with both collagen-induced arthritis (CIA) and human RA. DTH-arthritis is dependent on CD4+ cells for induction and can be successfully treated with TNFalpha-blocking biologics and dexamethasone. On the basis of our findings we believe that the DTH-arthritis model could hold potential in the preclinical screening of novel drugs targeting RA. The model is highly reproducible and has a high incidence rate with synchronised onset and progression, which strengthens its potential. PMID- 22676341 TI - Association between spinal loads and the psychophysical determination of maximum acceptable force during pushing tasks. AB - The objective of this study was to investigate potential associations between an individual's psychophysical maximum acceptable force (MAF) during pushing tasks and biomechanical tissue loads within the lumbar spine. Ten subjects (eight males, two females) pushed a cart with an unknown weight at one push every two minute for a distance of 3.9 m. Two independent variables were investigated, cart control and handle orientation while evaluating their association with the MAF. Dependent variables of hand force and tissue loads for each MAF determination and preceding push trial were assessed using a validated, electromyography-assisted biomechanical model that calculated spinal load distribution throughout the lumbar spine. Results showed no association between spinal loads and the MAF. Only hand forces were associated with the MAF. Therefore, MAFs may be dependent upon tactile sensations from the hands, not the loads on the spine and thus may be unrelated to risk of low back injury. Practitioner Summary: Pushing tasks have become common in manual materials handling (MMH) and these tasks impose different tissue loads compared to lifting tasks. Industry has commonly used the psychophysical tables for job assent and decision of MMH tasks. However, due to the biomechanical complexity of pushing tasks, psychophysics may be misinterpreting risk. PMID- 22676342 TI - Two new phenolic glycosides from Inula cappa DC. AB - Two new phenolic glycosides were isolated from the ethanol extract of the roots of Inula cappa DC. Their structures were defined as 4-[(6-O-(E)-caffeoyl)-beta-D glucopyranosyl]vanillic acid (1) and 3-O-[beta-D-apiofurarnosyl-(1-6)-beta-D glucopyranoxy]-6-hydroxy-p-cymene (2) on the basis of spectral analysis. PMID- 22676340 TI - Association between alcohol screening scores and mortality in black, Hispanic, and white male veterans. AB - BACKGROUND: Scores on the Alcohol Use Disorders Identification Test Consumption (AUDIT-C) questionnaire are associated with mortality, but whether or how associations vary across race/ethnicity is unknown. METHODS: Self-reported black (n = 13,068), Hispanic (n = 9,466), and white (n = 182,688) male Veterans Affairs (VA) outpatients completed the AUDIT-C via mailed survey. Logistic regression models evaluated whether race/ethnicity modified the association between AUDIT-C scores (0, 1 to 4, 5 to 8, and 9 to 12) and mortality after 24 months, adjusting for demographics, smoking, and comorbidity. RESULTS: Adjusted mortality rates were 0.036, 0.033, and 0.054, for black, Hispanic, and white patients with AUDIT C scores of 1 to 4, respectively. Race/ethnicity modified the association between AUDIT-C scores and mortality (p = 0.0022). Hispanic and white patients with scores of 0, 5 to 8, and 9 to 12 had significantly increased risk of death compared to those with scores of 1 to 4; Hispanic ORs: 1.93, 95% CI 1.50 to 2.49; 1.57, 1.07 to 2.30; 1.82, 1.04 to 3.17, respectively; white ORs: 1.34, 95% CI 1.29 to 1.40; 1.12, 1.03 to 1.21; 1.81, 1.59 to 2.07, respectively. Black patients with scores of 0 and 5 to 8 had increased risk relative to scores of 1 to 4 (ORs 1.28, 1.06 to 1.56 and 1.50, 1.13 to 1.99), but there was no significant increased risk for scores of 9 to 12 (ORs 1.27, 0.77 to 2.09). Post hoc exploratory analyses suggested an interaction between smoking and AUDIT-C scores might account for some of the observed differences across race/ethnicity. CONCLUSIONS: Among male VA outpatients, associations between alcohol screening scores and mortality varied significantly depending on race/ethnicity. Findings could be integrated into systems with automated risk calculators to provide demographically tailored feedback regarding medical consequences of drinking. PMID- 22676343 TI - Catumaxomab: in malignant ascites. AB - Catumaxomab is a rat/murine hybrid, trifunctional, bispecific (anti-human epithelial cell adhesion molecule [EpCAM] * anti-CD3) monoclonal antibody. Compared with paracentesis alone, paracentesis followed by catumaxomab therapy was associated with significant prolongation of paracentesis-free survival and time to repeat paracentesis in a randomized, open-label, multicentre, pivotal phase II/III trial in patients with recurrent symptomatic malignant ascites due to EpCAM-positive tumours who were resistant to conventional chemotherapy. The benefits of catumaxomab were seen across a broad range of epithelial ovarian and nonovarian cancers, and irrespective of whether or not catumaxomab recipients developed human anti-mouse antibodies. Combining catumaxomab with paracentesis also resulted in more pronounced and prolonged reductions in ascites signs and symptoms and a delayed deterioration in health-related quality of life compared with paracentesis alone. Despite the study not being designed or powered to evaluate overall survival, significant differences favouring the addition of catumaxomab to paracentesis were seen in analyses of the safety population and the subpopulation of patients with gastric cancer. Catumaxomab was generally well tolerated in the pivotal phase II/III trial. The most frequent adverse events attributed to catumaxomab treatment included cytokine-release-related symptoms, which were mostly of mild to moderate severity and manageable with standard symptomatic treatment. PMID- 22676344 TI - Genetic alterations in a primary medullary thyroid carcinoma and its lymph node metastasis in a patient with 15 years follow-up. AB - BACKGROUND: Association between DNA alterations and clinical parameters as recurrence, survival or prognosis has been found in a variety of tumors. A clear association between Medullary Thyroid Carcinoma (MTC) and RET oncogene mutation has been accepted. Specifically M918T RET mutation represents the main genetic event in most cases of sporadic MTC (SMTC) and limited chromosomal alterations analyses have been performed. METHODS: In the present work, a comparative genomic hybridization (CGH) study was performed using DNA from a primary tumor in a M918T RET mutation-positive SMTC patient and from its lymph node metastasis to investigate additional genetic alterations. We studied a patient with 15 years of follow-up and persistence of disease, confirmed by periodical elevated serum calcitonin (CT) levels. RESULTS: Only 3 chromosomal imbalances were identified in the primary tumor, gain of 18p, and loss of 6p and 16p region, whereas 25 chromosomal imbalances were identified in the metastasis (9 gains and 16 losses). CONCLUSION: The chromosomal changes 6p-, 16p-, 18p + could determine in part the oncogenic phenotype in the primary M918T RET positive tumor and probably related to persistence of high serum CT levels in this patient. The additional chromosomal changes observed could be related to the metastasis phenotype. We suggest that some genes mapped at 6p, 16p and 18p chromosomal regions, could act as genes associated to cancer and could be related to persistent SMTC and good prognosis. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1720753793691097. PMID- 22676345 TI - Psychosocial perspectives in the treatment of pediatric chronic pain. AB - Chronic pain in children and adolescents is associated with major disruption to developmental experiences crucial to personal adjustment, quality of life, academic, vocational and social success. Caring for these patients involves understanding cognitive, affective, social and family dynamic factors associated with persistent pain syndromes. Evaluation and treatment necessitate a comprehensive multimodal approach including psychological and behavioral interventions that maximize return to more developmentally appropriate physical, academic and social activities. This article will provide an overview of major psychosocial factors impacting on pediatric pain and disability, propose an explanatory model for conceptualizing the development and maintenance of pain and functional disability in medically difficult-to-explain pain syndromes, and review representative evidence-based cognitive behavioral and systemic treatment approaches for improving functioning in this pediatric population. PMID- 22676346 TI - Epiluminescence microscopy (dermoscopy) versus visual inspection during Mohs microscopic surgery of infiltrative basal cell carcinoma. AB - BACKGROUND: The initial stage of Mohs micrographic surgery (MMS) is usually outlined using visual inspection. Newer noninvasive models are available to the Mohs surgeon to determine initial margins before MMS. OBJECTIVE: To compare the final number of MMS stages performed using dermoscopy and visual inspection of infiltrative basal cell carcinoma (BCC). METHODS: Forty patients were randomized to two groups (dermoscopy, visual inspection) before MMS for infiltrative BCC. The final number of stages performed was recorded for each group. RESULTS: There were no statistically significant differences in the final number of stages when using dermoscopy and visual inspection. LIMITATIONS: Small sample sizes, comparison of different regions on the head and neck, and a single Mohs surgeon were the limiting factors in this study. CONCLUSIONS: There was no difference in the final number of stages between dermoscopy and visual inspection to determine the margins of previously biopsied infiltrative BCC. PMID- 22676347 TI - Polymer-supported stereoselective synthesis of benzimidazolinopiperazinones. AB - We describe the efficient synthesis of 4,7,8,10-tetrasubstituted-(((4S,10aS)-3 oxo-3,4,10,10a-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazin-2(1H)-yl)alkyl)amides on solid phase via tandem N-acyliminium ion cyclization-nucleophilic addition reactions. The synthesis proceeded with complete stereocontrol of a newly formed stereogenic center, provided crude material of high purity, and used commercially available building blocks under mild reaction conditions. PMID- 22676348 TI - Hydroxychloroquine improves insulin sensitivity in obese non-diabetic individuals. AB - INTRODUCTION: Hydroxychloroquine (HCQ) is a common disease modifying therapy for the treatment of rheumatoid arthritis (RA). Prior research suggests that HCQ may reduce the risk of diabetes mellitus in patients with RA. To investigate the mechanism of this effect, we examined the effect of HCQ on insulin resistance, insulin sensitivity, and pancreatic beta-cell secretion of insulin in non diabetic, obese subjects. METHODS: We recruited 13 obese, non-diabetic subjects without systemic inflammatory conditions for an open-label longitudinal study of HCQ 6.5 mg per kilogram per day for six weeks. Subjects underwent an oral glucose tolerance test at three time points: 0 weeks (pre-treatment with HCQ), 6 weeks (at the end of the HCQ treatment), and 12 weeks (6 weeks post HCQ-treatment). The Matsuda Insulin Sensitivity Index (ISI), HOMA-IR, and HOMA-B were compared across time-points. RESULTS: The mean age of the cohort was 49 years, 77% females and median body mass index was 36.1 kg/m2. After 6 weeks of HCQ therapy, ISI increased from a median (interquartile range) of 4.5 (2.3-7.8) to 8.9 (3.7-11.4) with a p-value of 0.040, and HOMA-IR decreased from a median of 2.1 (1.6-5.4) to 1.8 (1.02-2.1) with a p-value of 0.09. All these variables returned toward baseline at week 12. CONCLUSION: HCQ use for 6 weeks in non diabetic obese subjects was associated with a significant increase in ISI and trends toward reduced insulin resistance and insulin secretion. These data suggest that HCQ, a common medication used to treat RA, possesses beneficial effects upon insulin sensitization. Further study of the insulin sensitizing effects of HCQ in patients with RA is warranted. PMID- 22676349 TI - Domain-swapping of mesophilic xylanase with hyper-thermophilic glucanase. AB - BACKGROUND: Domain fusion is limited at enzyme one terminus. The issue was explored by swapping a mesophilic Aspergillus niger GH11 xylanase (Xyn) with a hyper-thermophilic Thermotoga maritima glucanase (Glu) to construct two chimeras, Xyn-Glu and Glu-Xyn, with an intention to create thermostable xylanase containing glucanase activity. RESULTS: When expressed in E. coli BL21(DE3), the two chimeras exhibited bi-functional activities of xylanase and glucanase. The Xyn Glu Xyn moiety had optimal reaction temperature (Topt) at 50 degrees C and thermal in-activation half-life (t1/2) at 50 degrees C for 47.6 min, compared to 47 degrees C and 17.6 min for the Xyn. The Glu-Xyn Xyn moiety had equivalent Topt to and shorter t1/2 (5.2 min) than the Xyn. Both chimera Glu moieties were more thermostable than the Glu, and the three enzyme Topt values were higher than 96 degrees C. The Glu-Xyn Glu moiety optimal pH was 5.8, compared to 3.8 for the Xyn-Glu Glu moiety and the Glu. Both chimera two moieties cooperated with each other in degrading substrates. CONCLUSIONS: Domain-swapping created different effects on each moiety properties. Fusing the Glu domain at C-terminus increased the xylanase thermostability, but fusing the Glu domain at N-terminus decreased the xylanase thermostability. Fusing the Xyn domain at either terminus increased the glucanase thermostability, and fusing the Xyn domain at C-terminus shifted the glucanase pH property 2 units higher towards alkaline environments. Fusing a domain at C-terminus contributes more to enzyme catalytic activity; whereas, fusing a bigger domain at N-terminus disturbs enzyme substrate binding affinity. PMID- 22676350 TI - Effect of 50 Hz electric field in diacylglycerol acyltransferase mRNA expression level and plasma concentration of triacylglycerol, free fatty acid, phospholipid and total cholesterol. AB - BACKGROUND: The effects of exposure to a 50 Hz electric field (EF) on plasma level of triacylglycerol, free fatty acids, total cholesterol and phospholipid and mRNA expression level of diacylglycerol acyltransferase (DGAT) 1 and 2 in liver and intestines from C57BL/6 J mice were studied. METHODS: The test was based on comparison between mice post treated with 50 Hz EF of 45 kV/m intensity for 30 min per day for 11 days or without EF. DGATs mRNA expression was analyzed by real-time quantitative polymerase chain reaction. RESULTS: There was no difference in the gene expression level of DGAT1 in liver and intestines. The DGAT2 gene expression level in liver derived from mice treated with EF was significantly lower than those in the control (P < 0.001). Both plasma total cholesterol (P < 0.01) and phospholipid (P < 0.05) in the group exposed to EF were lower than those in the control, but there was no difference in triacylglycerol or free fatty acid levels. CONCLUSION: Exposure to 50 Hz EF decrease the plasma levels of total cholesterol and phospholipids, and downregulated DGAT2 mRNA expression in liver. The mechanisms for the effects of EF on lipid metabolism are not well understand yet, but altered DGAT2 activity may be involved. PMID- 22676351 TI - Idiopathic hemorrhagic pericardial effusion as a precursor to epicardial lymphosarcoma in three cows. PMID- 22676352 TI - The role of Src kinase in the biology and pathogenesis of Acanthamoeba castellanii. AB - BACKGROUND: Acanthamoeba species are the causative agents of fatal granulomatous encephalitis in humans. Haematogenous spread is thought to be a primary step, followed by blood-brain barrier penetration, in the transmission of Acanthmaoeba into the central nervous system, but the associated molecular mechanisms remain unclear. Here, we evaluated the role of Src, a non-receptor protein tyrosine kinase in the biology and pathogenesis of Acanthamoeba. METHODS: Amoebistatic and amoebicidal assays were performed by incubating amoeba in the presence of Src kinase-selective inhibitor, PP2 (4-amino-5-(4-chlorophenyl)-7-(t butyl)pyrazolo[3,4-d]pyrimidine) and its inactive analog, PP3 (4-amino-7 phenylpyrazolo[3,4-d]pyrimidine). Using this inhibitor, the role of Src kinase in A. castellanii interactions with Escherichia coli was determined. Zymographic assays were performed to study effects of Src kinase on extracellular proteolytic activities of A. castellanii. The human brain microvascular endothelial cells were used to determine the effects of Src kinase on A. castellanii adhesion to and cytotoxicity of host cells. RESULTS: Inhibition of Src kinase using a specific inhibitor, PP2 (4-amino-5-(4 chlorophenyl)-7-(t-butyl)pyrazolo [3,4-d] pyrimidine) but not its inactive analog, PP3 (4-amino-7-phenylpyrazolo[3,4-d] pyrimidine), had detrimental effects on the growth of A. castellanii (keratitis isolate, belonging to the T4 genotype). Interestingly, inhibition of Src kinase hampered the phagocytic ability of A. castellanii, as measured by the uptake of non-invasive bacteria, but, on the contrary, invasion by pathogenic bacteria was enhanced. Zymographic assays revealed that inhibition of Src kinases reduced extracellular protease activities of A. castellanii. Src kinase inhibition had no significant effect on A. castellanii binding to and cytotoxicity of primary human brain microvascular endothelial cells, which constitute the blood-brain barrier. CONCLUSIONS: For the first time, these findings demonstrated that Src kinase is involved in A. castellanii proliferation, protease secretions and phagocytic properties. Conversely, invasion of Acanthamoeba by pathogenic bacteria was stimulated by Src kinase inhibition. PMID- 22676353 TI - Pressure-induced denaturation of beta-lactoglobulin in skim milk: effect of milk concentration. AB - The effect of milk concentration (10-40% TS) on the kinetics of the pressure induced denaturation of beta-lactoglobulin (beta-LG) was studied. The denaturation was found to be a second-order process at all milk concentrations and pressures. There was a change in pressure dependence of the rate constants for denaturation at about 300 MPa, and this effect became more pronounced as the milk concentration increased. At pressures >=300 MPa, a small effect of milk concentration was observed, with small decreases in the rate of denaturation as the milk concentration was increased above 20% TS. This was attributed to the lower pH as the milk concentration was increased. In contrast, at 200 MPa, beta LG denaturation was markedly retarded as the milk solids concentration was increased. This was attributed to the increased lactose concentration at higher milk concentrations. This would promote beta-LG dimerization at this pressure and this would stabilize the beta-LG to denaturation. PMID- 22676355 TI - Renal comorbidity after solid organ and stem cell transplantation. AB - After transplantation of solid organs or hematopoietic stem cells, a significant acute decrease in renal function occurs in the majority of patients. Depending on the degree of kidney injury, a large number of patients develop chronic kidney disease (CKD) and some develop end-stage renal disease requiring renal replacement therapy. The incidence varies depending on the transplanted organ, but important risk factors for the development of CKD are preexisting renal disease, hepatitis C, diabetes, hypertension, age, sex, posttransplant acute kidney injury and thrombotic microangiopathy. This review article focuses on the risk factors of posttransplant chronic kidney disease after organ transplantation, considering the current literature and integrates the incidence and the associated mortality rates of acute and chronic kidney disease. Furthermore, we introduce the RECAST (REnal Comorbidity After Solid organ and hematopoietic stem cell Transplantation) registry. PMID- 22676354 TI - Reasons physicians do not recommend and patients refuse adjuvant chemotherapy for stage III colon cancer: a population based chart review. AB - BACKGROUND: Surgery followed by adjuvant chemotherapy has been the standard of care for the treatment of stage III colon cancer since the early 1990's. Despite this, large proportions of patients do not receive adjuvant chemotherapy. We aimed to identify physicians' and patients' reasons for treatment decisions. METHODS: A retrospective population based study was conducted that included all surgically treated stage III colon cancer patients diagnosed in Alberta between 2002 and 2005 who had an oncologist-consult to discuss post-surgical treatment options. Patient demographics and stage were obtained from the Alberta Cancer Registry. Chart reviews were conducted to extract treatment details, the oncologists' reasons for not recommending chemotherapy, and patients' reasons for refusing chemotherapy. The number and proportion of patients who were not recommended or refused chemotherapy were calculated. RESULTS: A total of 613 patients had surgery followed by an oncologist-consult. Overall, 168 (27%) patients did not receive chemotherapy. It was not recommended for 111 (18%) patients; the most frequent reason was presence of one or more co-morbidities (34%) or combination of co-morbidity and age or frailty (22%). Fifty-eight (9%) patients declined chemotherapy, 22% of whom declined due to concerns about toxicity. CONCLUSION: Some co-morbidities are clinical indications for not receiving adjuvant chemotherapy, however, the high percentage of patients who were not recommended adjuvant chemotherapy due to co-morbidities according to clinical notes but who had a low Charlson co-morbidity score suggests variation in practice patterns of consulting oncologists. In addition, patients' reasons for refusing treatment need to be systematically assessed to ensure patients' preferences and treatment benefits are properly weighed when making treatment decisions. PMID- 22676356 TI - Adolescents' physical activity habits--results from a national health survey. AB - BACKGROUND: The MABAT Youth National Health and Nutrition Survey was conducted in Israel by the Ministry of Health and the Center for Disease Control. This article presents results of physical activity (PA) habits in Israel, in relation to recommendations by world health organizations. METHODS: Participants were 6274 adolescents, grades 7-12, enrolled in a cross-sectional, representative, school-based survey. Sufficient level of PA was defined as any moderate and vigorous level of PA that adds up daily to 60 min/day. Light PA was considered to be an insufficient level of PA. RESULTS: Only 10.5% of the participants reported performing sufficient PA. Large gender differences were found, with 17.7% of boys versus only 4.6% of girls meeting the guidelines. CONCLUSIONS: Results highlight the need to develop programmes for school children in Israel to promote PA. Such programmes have been initiated in many countries that have a large percentage of adolescents with a sedentary lifestyle. PMID- 22676357 TI - Treating hepatitis C: current standard of care and emerging direct-acting antiviral agents. AB - Summary. During the late 1990s and early 2000s, major advances were made in the treatment of patients with chronic hepatitis C virus (HCV) infection. Interferon, combination interferon plus ribavirin (RBV) and pegylated interferon plus RBV increased sustained virologic response (SVR) rates from ~5% to ~40-80%, depending on the genotype of HCV infection. Advances in molecular biology have allowed investigators to begin to understand the mechanisms of HCV infection and replication. Advances in understanding of viral kinetics have provided tools to identify patients who are most likely to attain SVR. With the advances in the science of HCV infection, the first part of the 21st century has seen the development and early introduction of a number of direct-acting antiviral (DAA) drugs. These novel medications interfere with critical steps in HCV replication and have the potential to significantly increase SVR rates. This article will review the key elements of HCV replication and evaluate the various classes of new and investigational DAA that have the potential to create a revolution in the management of patients with chronic hepatitis C. PMID- 22676358 TI - Methylenetetrahydrofolate reductase homozygosis and low-density lipoproteins in patients with genotype 1 chronic hepatitis C. AB - Methylenetetrahydrofolate reductase status, homocysteine and lipoproteins levels have been associated with severity of disease and both rapid and sustained virological response (SVR) in patients with genotype 1 chronic hepatitis C (CHC). We aimed to assess the association of homocysteine and MTHFR status with serum cholesterol levels and their potential links to both histological findings and virological response, in patients with genotype 1 hepatitis C virus (HCV). A total of 119 consecutive patients were evaluated by biopsy and metabolic measurements. A total of 103 healthy blood donors were used as controls. Serum homocysteine and MTHFR C677T mutation were also evaluated. All patients underwent antiviral therapy with PEG-IFN alfa-2a plus ribavirin. HCV-RNA was assessed at baseline, week 4, week 12, at the end of therapy and after 6 months of follow-up. Mean serum values of homocysteine were higher in patients than in controls (15.8 +/- 5.8 MUg/L vs 12.5 +/- 5.8 MUg/L; P < 0.001), with a similar CC, CT and TT MTHFR distribution (23.6%, 48.7% and 27.7% in G1-CHC vs 34%, 48.5% and 17.5% in controls; P = 0.14). In genotype 1, HCV MTHFR TT homozygosis was independently linked to higher LDL (OR 1.016; CI 1.002-1.031; P = 0.03), but not to homocysteine. No association were found between homocysteine, MTHFR and histological features or both rapid virological response (RVR) and SVR. Low cholesterol (OR 0.988, 95%CI 0.975-0.999, P = 0.04) was independently linked to severe fibrosis, and high LDL was the only independent positive predictors of both RVR and SVR (OR 1.036; 95%CI 1.017-1.055; P < 0.001; and OR 1.016; 95%CI 1.001-1.031; P = 0.04 respectively). In patients with genotype 1 hepatitis C, showing higher homocysteine serum levels than controls, MTHFR C677T homozygosis, via modulating cholesterol levels, could interfere with liver fibrosis and response to antiviral therapy. PMID- 22676359 TI - Role of Helicobacter pylori in patients with HCV-related chronic hepatitis and cirrhosis with or without hepatocellular carcinoma: possible association with disease progression. AB - The discovery of Helicobacter hepaticus as a causal agent of hepatitis and hepatocellular carcinoma (HCC) in mice has stimulated interest in looking for Helicobacter species in human liver samples. In this study, we searched for association between H. pylori and HCV-related liver disease. Liver specimens were collected from eighty-five patients; they were divided into five different groups according to liver pathology (METAVIR system). Group I (the 1st control group) consisted of 16 patients with chronic hepatitis C without histological activity. Group II consisted of 25 patients with chronic active hepatitis C, Group III, 17 patients with HCV-related cirrhosis and Group IV, 16 patients with HCV-related cirrhosis and HCC. Group V (2nd control group) consisted of 11 patients suffering from gastro duodenal and gall bladder diseases but negative for HCV. All cases were tested by polymerase chain reaction on liver samples for the presence of H. pylori DNA Cag A gene. Routine biochemical, radiological and RT-PCR for HCV RNA were also performed for all cases. The positivity of H. pylori PCR CagA gene in liver tissue was directly proportional to the severity of liver pathology, this being 75%, 52.9% and 32% in groups IV, III and II, respectively, which was more significant than the 1st and 2nd control groups (P < 0.001). There was a significant difference between H. pylori PCR values when compared to METAVIR staging (F) in different groups (P = 0.001). Helicobacter pylori PCR (Cag A gene) was positive in about 28.2% cases of late fibrosis (F3 + F4) while positivity was (5.9%) in early fibrosis (F1 + F2) (P = 0.0001). There was significant difference between H. pylori PCR (Cag A gene) in liver tissue and METAVIR activity in different groups (P = 0.002) as most of H. pylori PCR-positive cases were METAVIR activity A1 and A2 (15.3% and 12.9%, respectively). There was no association between H. pylori PCR and quantitative HCV RNA (P = 0.531). Also there was no significant difference of Child-Pugh staging in the H. pylori PCR-positive group when compared to the negative group (P = 0.996). There may be an association between the presence of H. pylori (Cag A gene) in the liver and disease progression in HCV-related chronic hepatitis and cirrhosis with and without HCC. PMID- 22676360 TI - Assessment of factors associated with pre-diabetes in HCV infection including direct and dynamic measurements of insulin action. AB - Although hepatitis C (HCV) is associated with diabetes, few studies have examined pre-diabetes in this population. We aimed to evaluate factors associated with pre diabetes in HCV-infected patients, including direct measurement of insulin action. Ninety-seven non-cirrhotic, non-diabetic and HCV-infected patients underwent clinical evaluation and oral glucose tolerance testing (OGTT). Insulin sensitivity was measured directly by steady-state plasma glucose (SSPG) concentration during insulin suppression test. Early phase and total insulin secretion were determined using OGTT. Rates of pre-diabetes were as follows: 21% impaired fasting glucose (IFG), 7% impaired glucose tolerance (IGT) and 9% combined IFG/IGT. Twelve percent of Caucasians, 50% of African Americans and 70% of Latinos had pre-diabetes (P = 0.002). Patient characteristics among the glucose metabolism categories were similar except those with combined IFG/IGT had a higher body mass index (BMI) vs normal glucose tolerance (NGT) (30 vs 26 kg/m(2), P = 0.007) and lower LDL vs NGT and IGT (74, 104 and 112 mg/dL, respectively, P <= 0.01). On multivariable analysis, non-Caucasian race (OR 23.1, P = 0.003), BMI (OR 3.4, P = 0.02) and greater liver inflammation (OR 7.9, P = 0.03) predicted IFG, whereas non-Caucasian race (OR 14.8, P = 0.01) and SSPG (OR 1.1 per 10 units, P = 0.01) predicted IGT. Early and total insulin secretion adjusted for the degree of insulin resistance was decreased in pre-diabetes compared with NGT (P = 0.01 and P = 0.02, respectively). Pre-diabetes is highly prevalent among HCV-infected patients, and in some instances, coincides with host responses to the virus. In most cases, however, factors that are associated with pre-diabetes in HCV-infected patients are similar to those observed in the non HCV population. PMID- 22676361 TI - The impact of fibrosis and steatosis on early viral kinetics in HCV genotype 1 infected patients treated with Peg-IFN-alfa-2a and ribavirin. AB - Hepatitis C viral (HCV) kinetics after initiation of interferon-based therapy provide valuable insights for understanding virus pathogenesis, evaluating treatment antiviral effectiveness and predicting treatment outcome. Adverse effects of liver fibrosis and steatosis on sustained virological response have been frequently reported, yet their impacts on the early viral kinetics remain unclear. In this study, associations between histology status and early viral kinetics were assessed in 149 HCV genotype 1-infected patients treated with pegylated interferon alfa-2a and ribavirin (DITTO trial). In multivariate analyses adjusted for critical factors such as IL28B genotype and baseline viral load, presence of significant fibrosis (Ishak stage > 2) was found to independently reduce the odds of achieving an initial reduction (calculated from day 0 to day 4) in HCV RNA of >=2 logIU/mL (adjusted OR 0.03, P = 0.004) but was not associated with the second-phase slope of viral decline (calculated from day 8 to day 29). On the contrary, presence of liver steatosis was an independent risk factor for not having a rapid second-phase slope, that is, >=0.3 logIU/mL/week (adjusted OR 0.22, P = 0.012) but was not associated with the first phase decline. Viral kinetic modelling theory suggests that significant fibrosis primarily impairs the treatment antiviral effectiveness in blocking viral production by infected cells, whereas the presence of steatosis is associated with a lower net loss of infected cells. Further studies will be necessary to identify the biological mechanisms underlain by these findings. PMID- 22676362 TI - Evolution of biomarkers of liver fibrosis and liver insufficiency in hepatitis C virus-infected patients treated with pegylated interferon plus ribavirin and rituximab. AB - Therapeutic options in hepatitis C virus (HCV)-related vasculitis may target the viral trigger using antiviral therapy [pegylated interferon plus ribavirin (PEG IFN/RBV)], and/or the downstream B-cell arm of autoimmunity with rituximab (RTX). To date, no study has compared the efficacy of RTX combined with PEG-IFN/RBV on biomarkers of liver insufficiency in patients with severe liver fibrosis. Twenty eight untreated HCV-related vasculitis patients with severe liver fibrosis (Metavir F3-F4) were included: 14 patients received RTX plus PEG-IFN/RBV and 14 patients PEG-IFN/RBV. The main clinical and biological data were recorded and compared at baseline, month 3 (M3), M12 and M24 of follow-up. Baseline epidemiological, clinical, virological and immunological features were similar between the groups. The virological response did not differ between cases and controls. The alanine aminotransferase (ALT) level and HCV viral load did not increase in patients treated with RTX. Serum albumin levels increased in patients treated with RTX at M3 and M6 (108% and 111% of baseline value; P = 0.06 and P = 0.13), whereas it was stable in patients treated without RTX. FibroTest values decreased from 0.70 at baseline to 0.59 at M3 (P = 0.5) and returned to 0.69 at M24 in the RTX-PEG-IFN/RBV group, whereas they were stable in the PEG-IFN/RBV group. RTX is safe in patients with severe HCV liver fibrosis and vasculitis. No beneficial effects of RTX were evidenced on liver fibrosis progression, but we found interesting correlations with the serum albumin level, FibroTest values and B-cell count. PMID- 22676363 TI - Cytokine profiles in high risk injection drug users suggests innate as opposed to adaptive immunity in apparent resistance to hepatitis C virus infection. AB - A cohort of injection drug users (IDU) have been identified who despite a long history of IDU and sharing of injecting equipment remain seronegative and aviraemic for hepatitis C virus (HCV). They have been termed HCV exposed uninfected (EU). The study of potential innate or adaptive immune mechanisms of resistance to HCV infection in this group is of interest. The aim of this study was to determine the levels of a broad range of cytokines in serum of exposed, uninfected individuals to ascertain whether there is a specific cytokine profile associated with apparent resistance to HCV. Sera from 22 EU individuals were analysed for a range of cytokines and chemokines, and compared to 16 treatment naive chronic HCV cases (HCV Ab+ RNA+), 16 individuals with spontaneous resolution of HCV (HCV-Ab+ and HCV-RNA-) and 10 healthy unexposed controls. EU subjects had strikingly higher levels of both IL-6 (on average more than 100 fold, P = 0.001) and IL-8 (on average more than 10-fold, P < 0.001) than the comparison groups. Additionally higher levels of tumour necrosis factor-alpha (TNF-alpha; on average up to threefold, P = 0.02) were seen in EU individuals. The levels of interferon-alpha (IFN-alpha) were upregulated in all HCV exposed groups in comparison to healthy controls (P = 0.013). Adaptive immune cytokine levels were no different between the groups. Cytokine profiling demonstrated raised levels of pro-inflammatory innate immune cytokines and chemokines in EU IDU, in particular interleukin-6 and interleukin-8. These findings suggest innate immune activation may be the key to prevention of infection in this cohort. PMID- 22676364 TI - Role of monokine induced by interferon-gamma in liver injury induced by hepatitis B virus in mice. AB - The chemokine monokine induced by interferon-gamma (Mig) is involved in the recruitment of inflammatory cells and liver injury during hepatitis B virus (HBV) infection. HBV protein X contributes to Mig expression in vitro by activation of nuclear factor (NF)-kappaB; however, the molecular mechanisms by which HBV induces Mig expression in vivo are unknown. In this paper, we established a mouse model for HBV study by tail vein injection of HBV genome-containing adenovirus vectors. Host immune response to the secreted hepatitis B surface antigen and e antigen was detected and serum alanine aminotransferase (ALT) was elevated at different time points. We also demonstrated that peripheral and intrahepatic Mig expression was increased after Ad-HBV infection. This was followed by inflammatory cell migration and formation of inflammatory foci in the liver. In addition, NF-kappaB p65 subunit translocated from the cytoplasm to the nucleus, and phosphoinositide 3-kinase/Akt, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) were to some extent phosphorylated after HBV injection. Following tail vein injection of Mig siRNA/in vivo-jetPEI-Gal complex, Mig expression was partially suppressed, inflammatory cell migration was inhibited, serum level of ALT were reduced. In conclusion, through NF-kappaB activation, HBV induced Mig expression in vivo, which recruited peripheral inflammatory cells to the liver and resulted in liver damage. Phosphorylation of phosphoinositide 3-kinase/Akt, ERK and JNK but not p38 might involved in the molecular mechanisms underlying HBV induced Mig expression in vivo. PMID- 22676365 TI - Maternal HBsAg status and infant size--a Faustian bargain? AB - Information on the impact of maternal hepatitis B virus (HBV) infection on pregnancy outcome is conflicting. Some studies reported an association with increased infant birthweight, which could be interpreted as advantageous to pregnancy. A retrospective study was performed to compare birthweight outcome between 6261 and 55,817 singleton pregnancies in mothers screened positive and negative for hepatitis B surface antigen (HBsAg), respectively. The HBsAg positive women were younger, had higher body mass index (BMI) and incidence of overweight, but less gestational weight gain, and were associated with increased macrosomia (birthweight >=4000 g) in mothers <35 years (odds ratio, OR, 1.28), BMI >=25 kg/m(2) (OR 1.24), without gestational diabetes mellitus (GDM, OR 1.19), and in male infants (OR 1.18). It was also associated with increased large-for gestational age (LGA, birthweight >90th percentile) infants in nulliparas (OR 1.13), age <35 years (OR 1.12), BMI >=25 kg/m(2) (OR 1.19), with (OR 1.36) and without (OR 1.09) GDM, and in male infants (OR 1.13). When the effects of high BMI, advanced age, GDM, and male infants were controlled for, positive HBsAg was significantly associated with macrosomic (adjusted odds ratio, aOR, 1.15) and LGA (aOR 1.11) infants. In view of the latest findings on the association between high infant birthweight with increased risk of obesity, diabetes mellitus, and various forms of malignancies from childhood to adulthood, further studies are warranted to determine if maternal hepatitis B infection would impact adversely on the long-term health of the offspring through its effect on increasing birthweight. PMID- 22676366 TI - Decreased maternal plasma apelin concentrations in preeclampsia. AB - BACKGROUND: Preeclampsia is a hypertensive disorder that complicates 3-7% of pregnancies. The development of preeclampsia has not been completely elucidated and current therapies are not broadly efficacious. The apelinergic system appears to be involved in hypertensive disorders and experimental studies indicate a role of this system in preeclampsia. Thus, an epidemiological evaluation of apelin protein concentration in plasma was conducted in case-control study of pregnant women. METHODS: Data and maternal plasma samples were collected from pregnant women with confirmed preeclampsia (n = 76) or normotensive controls (n = 79). Concentrations of apelin peptides were blindly measured using enzyme-linked immunosorbent assay. Data were subjected to statistical analyses. RESULTS: Plasma apelin concentrations, measured at delivery, were lower in preeclampsia cases compared with controls (mean +/- standard deviation: 0.66 +/- 0.29 vs. 0.78 +/- 0.31 ng/mL, p = 0.02). After controlling for confounding by maternal age, smoking status, and pre-pregnancy body mass index, odds of preeclampsia were 48% lower for women with high versus low plasma apelin (>=0.73 vs. <0.73 ng/mL) concentrations. CONCLUSION: Reduced circulating apelin peptides may be associated with preeclampsia. The apelinergic system should be further investigated to elucidate its role in preclampsia and other hypertensive maternal disorders. PMID- 22676367 TI - Virulence genes and pathogenicity islands in environmental Vibrio strains nonpathogenic to humans. AB - Most Vibrio species in autochthonous marine microbial communities, such as Vibrio alginolyticus, Vibrio harveyi, Vibrio anguillarum among others, are considered nonpathogenic for humans. However, because many bacterial virulence genes are located in mobile genetic elements, the acquisition of mobile DNA could mediate the appearance of virulent or more virulent strains even in a species defined as nonpathogenic. In this study, we screened a collection of marine nonpathogenic Vibrio strains isolated in the area of the Venetian Lagoon for the presence of virulence and fitness genes usually present in Vibrio cholerae and Vibrio parahaemolyticus clinical isolates. More than one-third of the strains tested positive for the presence of at least one of the potential virulence/fitness genes with the gene encoding the V. cholerae neuraminidase the most frequently detected. Moreover, 13 of the environmental strains carried modified versions of the V. cholerae pathogenicity island VPI-2, and four of them also contained partial fragments of the V. parahaemolyticus Vp-PAI. The data obtained support the view of nonpathogenic Vibrio strains as a significant reservoir of virulence and fitness genes. The emergence of environmental bacteria with new virulence traits might constitute a direct concern for public health and a risk for human health. PMID- 22676368 TI - Experimental study of crossover from capillary to viscous fingering for supercritical CO2-water displacement in a homogeneous pore network. AB - Carbon sequestration in saline aquifers involves displacing brine from the pore space by supercritical CO(2) (scCO(2)). The displacement process is considered unstable due to the unfavorable viscosity ratio between the invading scCO(2) and the resident brine. The mechanisms that affect scCO(2)-water displacement under reservoir conditions (41 degrees C, 9 MPa) were investigated in a homogeneous micromodel. A large range of injection rates, expressed as the dimensionless capillary number (Ca), was studied in two sets of experiments: discontinuous-rate injection, where the micromodel was saturated with water before each injection rate was imposed, and continuous-rate injection, where the rate was increased after quasi-steady conditions were reached for a certain rate. For the discontinuous-rate experiments, capillary fingering and viscous fingering are the dominant mechanisms for low (logCa <= -6.61) and high injection rates (logCa >= 5.21), respectively. Crossover from capillary to viscous fingering was observed for logCa = -5.91 to -5.21, resulting in a large decrease in scCO(2) saturation. The discontinuous-rate experimental results confirmed the decrease in nonwetting fluid saturation during crossover from capillary to viscous fingering predicted by numerical simulations by Lenormand et al. (J. Fluid Mech.1988, 189, 165-187). Capillary fingering was the dominant mechanism for all injection rates in the continuous-rate experiment, resulting in monotonic increase in scCO(2) saturation. PMID- 22676369 TI - Electrodeposition of copper on a Pt(111) electrode in sulfuric acid containing poly(ethylene glycol) and chloride ions as probed by in situ STM. AB - This study employed real-time in situ STM imaging to examine the adsorption of PEG molecules on Pt(111) modified by a monolayer of copper adatoms and the subsequent bulk Cu deposition in 1 M H(2)SO(4) + 1 mM CuSO(4)+ 1 mM KCl + 88 MUM PEG. At the end of Cu underpotential deposition (~0.35 V vs Ag/AgCl), a highly ordered Pt(111)-(?3 * ?7)-Cu + HSO(4)(-) structure was observed in 1 M H(2)SO(4) + 1 mM CuSO(4). This adlattice restructured upon the introduction of poly(ethylene glycol) (PEG, molecular weight 200) and chloride anions. At the onset potential for bulk Cu deposition (~0 V), a Pt(111)-(?3 * ?3)R30 degrees -Cu + Cl(-) structure was imaged with a tunneling current of 0.5 nA and a bias voltage of 100 mV. Lowering the tunneling current to 0.2 nA yielded a (4 * 4) structure, presumably because of adsorbed PEG200 molecules. The subsequent nucleation and deposition processes of Cu in solution containing PEG and Cl(-) were examined, revealing the nucleation of 2- to 3-nm-wide CuCl clusters on an atomically smooth Pt(111) surface at overpotentials of less than 50 mV. With larger overpotential (eta > 150 mV), Cu deposition seemed to bypass the production of CuCl species, leading to layered Cu deposition, starting preferentially at step defects, followed by lateral growth to cover the entire Pt electrode surface. These processes were observed with both PEG200 and 4000, although the former tended to produce more CuCl nanoclusters. Raising [H(2)SO(4)] to 1 M substantiates the suppressing effect of PEG on Cu deposition. This STM study provided atomic- or molecular-level insight into the effect of PEG additives on the deposition of Cu. PMID- 22676370 TI - Formulation of liposomes gels of paeonol for transdermal drug delivery by Box Behnken statistical design. AB - The aim of this study was to design and optimize a transdermal liposomes gel formulation for paeonol (PAE). A three-factor, three-level Box-Behnken design was used to derive a second-order polynomial equation to construct three-dimensional (3-D) contour plots for prediction of responses. Independent variables studied were the DC-Chol concentration (X1), molar ratio of lipid/drug (X2), and the polymer concentration (X3), and the levels of each factor were low, medium, and high. The dependent variables studied were the encapsulation efficiency (%EE) of PAE (Y1), flux of PAE (Y2), and viscosity of the gels (Y3). Response surface plots were drawn and statistical validity of the polynomials was established to find the compositions of optimized formulation, which was evaluated using the Franz diffusion cell. The %EE of PAE increased proportionally with the molar ratio of lipid/drug, but decreased with polymer concentration, whereas the flux of PAE increased proportionally with polymer concentration and the DC-Chol concentration. The viscosity of gels increased with the polymer concentration. Gels showed a non-Fickian diffusion release mechanism for PAE, and the in vitro release profiles were fit for Higuchi's order model. The design demonstrated the role of the derived polynomial equation and 3-D contour plots in predicting the values of dependent variables for the preparation and optimization of gel formulation for transdermal drug release. PMID- 22676372 TI - PollenCALC: software for estimation of pollen compatibility of self-incompatible allo- and autotetraploid species. AB - BACKGROUND: Self-incompatibility (SI) is a biological mechanism to avoid inbreeding in allogamous plants. In grasses, this mechanism is controlled by a two-locus system (S-Z). Calculation of male and female gamete frequencies is complex for tetraploid species. We are not aware of any software available for predicting pollen haplotype frequencies and pollen compatibility in tetraploid species. RESULTS: PollenCALC is a software tool written in C++ programming language that can predict pollen compatibility percentages for polyploid species with a two-locus (S, Z) self-incompatibility system. The program predicts pollen genotypes and frequencies based on defined meiotic parameters for allo- or autotetraploid species with a gametophytic S-Z SI system. These predictions can be used to obtain expected values for for diploid and for (allo- or autotetraploidy SI grasses. CONCLUSION: The information provided by this calculator can be used to predict compatibility of pair-crosses in plant breeding applications, to analyze segregation distortion for S and Z genes, as well as linked markers in mapping populations, hypothesis testing of the number of S and Z alleles in a pair cross, and the underlying genetic model. PMID- 22676373 TI - Pyrene-POSS nanohybrid as a dispersant for carbon nanotubes in solvents of various polarities: its synthesis and application in the preparation of a composite membrane. AB - In this study we report the preparation of nanohybrid dispersant molecules based on pyrene and polyhedral oligomeric silsesquioxanes for non-covalent functionalization of multi-walled carbon nanotubes (MWCNTs). The prepared dispersant improves the dispersion of MWCNTs in organic solvents with very different polarities such as tetrahydrofuran, toluene, and n-hexane. The functionalized MWCNTs were used to introduce conductivity into polydimethylsiloxane membranes which can be used for electrostatic discharge applications. PMID- 22676371 TI - Translating neurotrophic and cellular plasticity: from pathophysiology to improved therapeutics for bipolar disorder. AB - OBJECTIVE: Bipolar disorder (BD) likely involves, at a molecular and cellular level, dysfunctions of critical neurotrophic, cellular plasticity and resilience pathways and neuroprotective processes. Therapeutic properties of mood stabilizers are presumed to result from a restoration of the function of these altered pathways and processes through a wide range of biochemical and molecular effects. We aimed to review the altered pathways and processes implicated in BD, such as neurotrophic factors, mitogen-activated protein kinases, Bcl-2, phosphoinositol signaling, intracellular calcium and glycogen synthase kinase-3. METHODS: We undertook a literature search of recent relevant journal articles, book chapter and reviews on neurodegeneration and neuroprotection in BD. Search words entered were 'brain-derived neurotrophic factor,''Bcl-2,''mitogen-activated protein kinases,''neuroprotection,''calcium,''bipolar disorder,''mania,' and 'depression.' RESULTS: The most consistent and replicated findings in the pathophysiology of BD may be classified as follows: i) calcium dysregulation, ii) mitochondrial/endoplasmic reticulum dysfunction, iii) glial and neuronal death/atrophy and iv) loss of neurotrophic/plasticity effects in brain areas critically involved in mood regulation. In addition, the evidence supports that treatment with mood stabilizers; in particular, lithium restores these pathophysiological changes. CONCLUSION: Bipolar disorder is associated with impairments in neurotrophic, cellular plasticity and resilience pathways as well as in neuroprotective processes. The evidence supports that treatment with mood stabilizers, in particular lithium, restores these pathophysiological changes. Studies that attempt to prevent (intervene before the onset of the molecular and cellular changes), treat (minimize severity of these deficits over time), and rectify (reverse molecular and cellular deficits) are promising therapeutic strategies for developing improved treatments for bipolar disorder. PMID- 22676374 TI - Game theory sheds new light on ecological responses to current climate change when phenology is historically mismatched. AB - Phenological changes are well documented biological effects of current climate change but their adaptive value and demographic consequences are poorly known. Game theoretical models have shown that deviating from the fitness-maximising phenology can be evolutionary stable under frequency-dependent selection. We study eco-evolutionary responses to climate change when the historical phenology is mismatched in this way. For illustration we model adaptation of arrival dates in migratory birds that compete for territories at their breeding grounds. We simulate climate change by shifting the timing and the length of the favourable season for breeding. We show that initial trends in changes of population densities can be either reinforced or counteracted during the ensuing evolutionary adaptation. We find in total seven qualitatively different population trajectories during the transition to a new evolutionary equilibrium. This surprising diversity of eco-evolutionary responses provides adaptive explanations to the observed variation in phenological responses to recent climate change. PMID- 22676375 TI - Mohs micrographic surgery for cutaneous lymphadenoma. AB - Cutaneous lymphadenoma clinically present as pink papules or plaques resembling a basal cell carcinoma on the head and neck of young adults. Surgical excision is the treatment for these benign tumors. Cutaneous lymphadenoma may occur in an anatomically sensitive area, where margin control and conservative excision are indicated. Although not previously described in the literature, Mohs micrographic surgery (MMS) is a treatment option for cutaneous lymphadenoma. We present a series of three individuals with cutaneous lymphadenoma treated with MMS. PMID- 22676376 TI - General diastereoselective synthetic approach toward isospongian diterpenes. Synthesis of (-)-marginatafuran, (-)-marginatone, and (-)-20-acetoxymarginatone. AB - This work describes a synthetic approach to the carbocyclic skeleton of isospongian diterpenes that uses the commercially available monoterpene (S) carvone as a C-ring synthon, which is incorporated into the tetracyclic isospongian framework via a C->ABC->ABCD ring annulation strategy using intramolecular Diels-Alder and ring-closing metathesis reactions. This approach has been successfully used to prepare both the title natural isospongians and several nonnatural oxygenated analogues. A preliminary evaluation of the inhibitory activity of the small collection of synthesized isospongians on the mammalian mitochondrial respiratory chain revealed that most were able to inhibit the integrated electron transfer chain (NADH oxidase activity) in the micromolar range. PMID- 22676377 TI - Application of induced pluripotent stem cells in generation of a tissue engineered tooth-like structure. AB - Stem cells, such as adult stem cells or embryonic stem cells, are the most important seed cells employed in tooth tissue engineering. Even though dental derived stem cells are a good source of seed cells for such procedures, they are not often used in clinical applications because of the limited supply. Induced pluripotent stem (iPS) cells, with their high proliferation and differentiation ability, are now considered a promising alternative. The objectives of this study were to assess the role of iPS cells in tooth tissue engineering. We used real time polymerase chain reaction to confirm that mouse iPS (miPS) cells can be induced to express both odontogenic and osteogenic gene profiles. We then established a tooth germ model and transplanted the recombinant tooth germ into a mouse subrenal capsule for 4 weeks to reproduce early-tooth organogenesis. After 4 weeks, hematoxylin and eosin staining results showed newly formed bone-like and dental pulp-like areas. Further immunohistochemical staining confirmed that osteopontin was present in the apical part of the tooth-like structure. These results demonstrate that miPS cells have the potential to differentiate into odontogenic cells, confirming that they could be a new source of seed cells for use in tooth tissue engineering. PMID- 22676379 TI - A usability study of patients setting up a cardiac event loop recorder and BlackBerry gateway for remote monitoring at home. AB - This article reports on a usability study of remote noninvasive cardiac testing in homes. We studied the Vitaphone 3100BT (Bluetooth(r)) event loop recorder (Vitaphone GmbH, Mannheim, Germany) and paired BlackBerry(r) CurveTM 8520 smartphone (Research In Motion, Ltd., Waterloo, ON, Canada). This application requires independent device set-up by patients in their own homes following receipt by mail out of the kit (instructions plus the event loop recorder and smartphone). The case studies of five participants, each with varying experience with technology, were documented as they interacted with the devices. Participants were videotaped following written instructions as they performed a "think aloud" procedure while completing 20 device set-up tasks. Interviews provided insight into how the independent device set-up and processes could be improved. This study concluded that gender, age, and familiarity with technology seemed to influence the participants' abilities to successfully set up these devices and that sending the kit by mail appeared to be an acceptable strategy to provide remote noninvasive cardiac diagnostic services. This study provides a foundation for future research assessing usability of mobile healthcare technology. PMID- 22676378 TI - Retinoic acid and liver X receptor agonist synergistically inhibit HIV infection in CD4+ T cells by up-regulating ABCA1-mediated cholesterol efflux. AB - BACKGROUND: Retinoic acids regulate the reverse cholesterol transport by inducing the ATP binding cassette transporter A1 (ABCA1) dependent cholesterol efflux in macrophages, neuronal as well as intestine cells. In the present study, we aim to test the effect of all trans retinoic acid (ATRA) on ABCA1 expression in human CD4+ T cells and the involvement of cholesterol in ATRA mediated anti-HIV effect. RESULTS: Treatment with ATRA dramatically up-regulated ABCA1 expression in CD4+ T cells in a time and dose dependent manner. The expression of ABCA1 paralleled with increased ABCA1-dependent cholesterol efflux. This induction was dependent on T cell receptor (TCR) signaling and ATRA failed to induce ABCA1 expression in resting T cells. Moreover, ATRA and liver X receptor (LXR) agonist-TO-901317 together had synergistic effect on ABCA1 expression as well as cholesterol efflux. Increased ABCA1 expression was associated with lower cellular cholesterol staining. Cells treated with either ATRA or TO-901317 were less vulnerable to HIV 1 infection. Combination of retinoic acid and TO-901317 further inhibited HIV-1 entry and their inhibitory effects could be reversed by cholesterol replenishment. METHODS: ABCA1 RNA and protein were determined by real-time PCR and immuno blot methods in cells treated with ATRA. Cholesterol efflux rate was measured in cells treated with ATRA and TO-901317. CONCLUSIONS: ATRA up-regulates ABCA1 expression and cholesterol efflux in CD4+ T cells and combination of ATRA and liver X receptor (LXR) agonist further enhanced these effects. Increased cholesterol efflux contributed to reduced HIV-1 entry, suggesting that anti-HIV effect of ATRA is mediated through ABCA1. PMID- 22676380 TI - Under-diagnosis of pain by primary physicians and late referral to a palliative care team. AB - BACKGROUND: Under-diagnosis of pain is a serious problem in cancer care. Accurate pain assessment by physicians may form the basis of effective care. The aim of this study is to examine the association between late referral to a Palliative Care Team (PCT) after admission and the under-diagnosis of pain by primary physicians. METHODS: This retrospective study was performed in the Teikyo University teaching-hospital for a period of 20 months. We investigated triads composed of 213 adult cancer inpatients who had coexisting moderate or severe pain at the initial PCT consultation, 77 primary physicians, and 4 palliative care physicians. The outcome of the present study was the under-diagnosis of pain by primary physicians with routinely self-completed standard format checklists. The checklists included coexisting pain documented independently by primary and palliative care physicians at the time of the initial PCT consultation. Under diagnosis of pain was defined as existing pain diagnosed by the palliative care physicians only. Late referral to PCTs after admission was defined as a referral to the PCT at >=20 days after admission. Because the two groups displayed significantly different regarding the distributions of the duration from admission to referral to PCTs, we used 20 days as the cut-off point for "late referral." RESULTS: Accurate pain assessment was observed in 192 triads, whereas 21 triads displayed under-diagnosis of pain by primary physicians. Under diagnosis of pain by primary physicians was associated with a longer duration between admission and initial PCT consultation, compared with accurate pain assessment (25 days versus 4 days, p < 0.0001). After adjusting for potential confounding factors, under-diagnosis of pain by the primary physicians was significantly associated with late (20 or more days) referral to a PCT (adjusted odds ratio, 2.91; 95% confidence interval, 1.27 - 6.71). Other factors significantly associated with under-diagnosis of pain were coexisting delirium and case management by physicians with < 6 years of clinical experience. CONCLUSIONS: Under-diagnosis of pain by primary physicians was associated with late referral to PCTs. Shortening the duration from admission to referral to PCTs, and increasing physicians' awareness of palliative care may improve pain management for cancer patients. PMID- 22676381 TI - Comprehensive approach to intrinsic charge carrier mobility in conjugated organic molecules, macromolecules, and supramolecular architectures. AB - Si-based inorganic electronics have long dominated the semiconductor industry. However, in recent years conjugated polymers have attracted increasing attention because such systems are flexible and offer the potential for low-cost, large area production via roll-to-roll processing. The state-of-the-art organic conjugated molecular crystals can exhibit charge carrier mobilities (MU) that nearly match or even exceed that of amorphous silicon (1-10 cm(2) V(-1) s(-1)). The mean free path of the charge carriers estimated from these mobilities corresponds to the typical intersite (intermolecular) hopping distances in conjugated organic materials, which strongly suggests that the conduction model for the electronic band structure only applies to MU > 1 cm(2) V(-1) s(-1) for the translational motion of the charge carriers. However, to analyze the transport mechanism in organic electronics, researchers conventionally use a disorder formalism, where MU is usually less than 1 cm(2) V(-1) s(-1) and dominated by impurities, disorders, or defects that disturb the long-range translational motion. In this Account, we discuss the relationship between the alternating-current and direct-current mobilities of charge carriers, using time resolved microwave conductivity (TRMC) and other techniques including field effect transistor, time-of-flight, and space-charge limited current. TRMC measures the nanometer-scale mobility of charge carriers under an oscillating microwave electric field with no contact between the semiconductors and the metals. This separation allows us to evaluate the intrinsic charge carrier mobility with minimal trapping effects. We review a wide variety of organic electronics in terms of their charge carrier mobilities, and we describe recent studies of macromolecules, molecular crystals, and supramolecular architecture. For example, a rigid poly(phenylene-co-ethynylene) included in permethylated cyclodextrin shows a high intramolecular hole mobility of 0.5 cm(2) V(-1) s(-1), based on a combination of flash-photolysis TRMC and transient absorption spectroscopy (TAS) measurements. Single-crystal rubrene showed an ambipolarity with anisotropic charge carrier transport along each crystal axis on the nanometer scale. Finally, we describe the charge carrier mobility of a self assembled nanotube consisting of a large pi-plane of hexabenzocoronene (HBC) partially appended with an electron acceptor. The local (intratubular) charge carrier mobility reached 3 cm(2) V(-1) s(-1) for the nanotubes that possessed well-ordered pi-stacking, but it dropped to 0.7 cm(2) V(-1) s(-1) in regions that contained greater amounts of the electron acceptor because those molecules reduced the structural integrity of pi-stacked HBC arrays. Interestingly, the long-range (intertubular) charge carrier mobility was on the order of 10(-4) cm(2) V(-1) s(-1) and monotonically decreased when the acceptor content was increased. These results suggest the importance of investigating charge carrier mobilities by frequency-dependent charge carrier motion for the development of more efficient organic electronic devices. PMID- 22676383 TI - Properties and usefulness of aggregates of synovial mesenchymal stem cells as a source for cartilage regeneration. AB - INTRODUCTION: Transplantation of mesenchymal stem cells (MSCs) derived from synovium is a promising therapy for cartilage regeneration. For clinical application, improvement of handling operation, enhancement of chondrogenic potential, and increase of MSCs adhesion efficiency are needed to achieve a more successful cartilage regeneration with a limited number of MSCs without scaffold. The use of aggregated MSCs may be one of the solutions. Here, we investigated the handling, properties and effectiveness of aggregated MSCs for cartilage regeneration. METHODS: Human and rabbit synovial MSCs were aggregated using the hanging drop technique. The gene expression changes after aggregation of synovial MSCs were analyzed by microarray and real time RT-PCR analyses. In vitro and in vivo chondrogenic potential of aggregates of synovial MSCs was examined. RESULTS: Aggregates of MSCs cultured for three days became visible, approximately 1 mm in diameter and solid and durable by manipulation; most of the cells were viable. Microarray analysis revealed up-regulation of chondrogenesis-related, anti inflammatory and anti-apoptotic genes in aggregates of MSCs. In vitro studies showed higher amounts of cartilage matrix synthesis in pellets derived from aggregates of MSCs compared to pellets derived from MSCs cultured in a monolayer. In in vivo studies in rabbits, aggregates of MSCs could adhere promptly on the osteochondral defects by surface tension, and stay without any loss. Transplantation of aggregates of MSCs at relatively low density achieved successful cartilage regeneration. Contrary to our expectation, transplantation of aggregates of MSCs at high density failed to regenerate cartilage due to cell death and nutrient deprivation of aggregates of MSCs. CONCLUSIONS: Aggregated synovial MSCs were a useful source for cartilage regeneration considering such factors as easy preparation, higher chondrogenic potential and efficient attachment. PMID- 22676384 TI - Cyclodextrin-scaffolded alamethicin with remarkably efficient membrane permeabilizing properties and membrane current conductance. AB - Bacterial resistance to classical antibiotics is a serious medical problem, which continues to grow. Small antimicrobial peptides represent a potential solution and are increasingly being developed as novel therapeutic agents. Many of these peptides owe their antibacterial activity to the formation of trans-membrane ion channels resulting in cell lysis. However, to further develop the field of peptide antibiotics, a thorough understanding of their mechanism of action is needed. Alamethicin belongs to a class of peptides called peptaibols and represents one of these antimicrobial peptides. To examine the dynamics of assembly and to facilitate a thorough structural evaluation of the alamethicin ion-channels, we have applied click chemistry for the synthesis of templated alamethicin multimers covalently attached to cyclodextrin-scaffolds. Using oriented circular dichroism, calcein release assays, and single-channel current measurements, the alpha-helices of the templated multimers were demonstrated to insert into lipid bilayers forming highly efficient and remarkably stable ion channels. PMID- 22676385 TI - Reimbursement decisions of the All Wales Medicines Strategy Group: influence of policy and clinical and economic factors. AB - BACKGROUND: There have been several explorations of factors influencing the reimbursement decisions of the National Institute for Health and Clinical Excellence (NICE) but not of other UK-based health technology assessment (HTA) organizations. OBJECTIVE: This study aimed to explore the factors influencing the recommendations of the All Wales Medicines Strategy Group (AWMSG) on the use of new medicines in Wales. METHODS: Based on public data, logistic regression models were developed to evaluate the influence of cost effectiveness, the quality and quantity of clinical evidence, disease characteristics (including rarity), budget impact, and a range of other factors on the recommendations of AWMSG and its subcommittee, the New Medicines Group (NMG). RESULTS: Multivariate analyses of 47 AWMSG appraisals between 2007-9 correctly predicted 87% of decisions. The results are suggestive of a positive influence on recommendations of the presence of probabilistic sensitivity analyses (PSAs) but, counter-intuitively, a statistically significant negative influence of evidence from high-quality randomized controlled trials (RCTs) [odds ratio 0.059; 95% CI 0.005, 0.699]. This latter observation may be attributed to our strict definition of high quality, which excluded the use of surrogate endpoints. Putative explanatory variables, including cost effectiveness, budget impact, underlying disease characteristics and 'ultra'-orphan drug status were not statistically significant predictors of final AWMSG decisions based on our dataset. Univariate analyses indicate that medicines with negative recommendations had significantly higher incremental cost effectiveness ratios than those with positive recommendations, consistent with the pursuit of economic efficiency. There is also evidence that AWMSG considers equity issues via an ultra-orphan drugs policy. CONCLUSIONS: Consideration of decision uncertainty via PSA appears to positively influence the reimbursement decisions of AWMSG. The significant negative impact of the presence of high quality RCTs, and the lack of a significant positive impact of other expected factors, may reflect issues in the plausibility of supporting evidence for medicines that received negative recommendations. Furthermore, it serves to emphasize the difficulties in applying the usual hierarchies of evidence to the HTA process, and in particular to the appraisal of high-cost specialist medicines close to market launch. PMID- 22676386 TI - Successful use of infliximab in a patient with recalcitrant folliculitis decalvans. PMID- 22676387 TI - Automated telecommunication to obtain longitudinal follow-up in a multicenter cross-sectional COPD study. AB - BACKGROUND: It can be challenging to maintain longitudinal follow-up of subjects in clinical studies. COPDGene is a multicenter, observational study designed to identify genetic factors associated with COPD and to characterize COPD-related phenotypes. To obtain follow-up data on patient's vital status and outcomes, the COPDGene Longitudinal Follow-up (LFU) Program was developed to supplement its parent study. METHODS/RESULTS: We used a telecommunication system that employed automated telephone contact or web-based questions to obtain longitudinal follow up data in our subjects. A branching questionnaire asked about exacerbations, new therapies, smoking status, development of co-morbid conditions, and general health status. Study coordinators contacted subjects who did not respond to one of the automated methods. We enrolled 10,383 subjects in the COPDGene study. As of August 29, 2011, 7,959 subjects completed 19,955 surveys. On the first survey, 68.8% of subjects who completed their survey did so by electronic means, while 31.3% required coordinator phone follow-up. On each subsequent survey the number of subjects who completed their survey by electronic means increased, while the number of subjects who required coordinator follow-up decreased. Despite many of the patients in the cohort being chronically ill and elderly, there was broad acceptance of the system with over half the cohort using electronic response methods. CONCLUSIONS: The COPDGene LFU Study demonstrated that telecommunications was an effective way to obtain longitudinal follow-up of subjects in a large multicenter study. Web-based and automated phone contacts are accepted by research subjects and could serve as a model for LFU in future studies. PMID- 22676388 TI - Improved bioavailability of dietary phenolic acids in whole grain barley and oat groat following fermentation with probiotic Lactobacillus acidophilus , Lactobacillus johnsonii , and Lactobacillus reuteri. AB - The aim of this study was to improve the bioavailability of the dietary phenolic acids in flours from whole grain barley and oat groat following fermentation with lactic acid bacteria (LAB) exhibiting high feruloyl esterase activity (FAE). The highest increase of free phenolic acids was observed after fermentation with three probiotic strains, Lactobacillus johnsonii LA1, Lactobacillus reuteri SD2112, and Lactobacillus acidophilus LA-5, with maximum increases from 2.55 to 69.91 MUg g(-1) DM and from 4.13 to 109.42 MUg g(-1) DM in whole grain barley and oat groat, respectively. Interestingly, higher amounts of bound phenolic acids were detected after both water treatment and LAB fermentation in whole grain barley, indicating higher bioaccessibility, whereas some decrease was detected in oat groat. To conclude, cereal fermentation with specific probiotic strains can lead to significant increase of free phenolic acids, thereby improving their bioavailability. PMID- 22676390 TI - Synthesis of 3-substituted isocoumarins via a cascade intramolecular Ullmann-type coupling-rearrangement process. AB - A simple and highly efficient strategy for the synthesis of 3-substituted isocoumarins through a copper(I)-catalyzed reaction of 1-(2-halophenyl)-1,3 diones has been developed. The procedure is based on a cascade copper-catalyzed intramolecular Ullmann-type C-arylation and rearrangement process. This methodology is tolerant of a wide range of substrates and applicable to library synthesis. PMID- 22676389 TI - Detoxification enzymes associated with insecticide resistance in laboratory strains of Anopheles arabiensis of different geographic origin. AB - BACKGROUND: The use of insecticides to control malaria vectors is essential to reduce the prevalence of malaria and as a result, the development of insecticide resistance in vector populations is of major concern. Anopheles arabiensis is one of the main African malaria vectors and insecticide resistance in this species has been reported in a number of countries. The aim of this study was to investigate the detoxification enzymes that are involved in An. arabiensis resistance to DDT and pyrethroids. METHODS: The detoxification enzyme profiles were compared between two DDT selected, insecticide resistant strains of An. arabiensis, one from South Africa and one from Sudan, using the An. gambiae detoxification chip, a boutique microarray based on the major classes of enzymes associated with metabolism and detoxification of insecticides. Synergist assays were performed in order to clarify the roles of over-transcribed detoxification genes in the observed resistance phenotypes. In addition, the presence of kdr mutations in the colonies under investigation was determined. RESULTS: The microarray data identifies several genes over-transcribed in the insecticide selected South African strain, while in the Sudanese population, only one gene, CYP9L1, was found to be over-transcribed. The outcome of the synergist experiments indicate that the over-transcription of detoxification enzymes is linked to deltamethrin resistance, while DDT and permethrin resistance are mainly associated with the presence of the L1014F kdr mutation. CONCLUSIONS: These data emphasise the complexity associated with resistance phenotypes and suggest that specific insecticide resistance mechanisms cannot be extrapolated to different vector populations of the same species. PMID- 22676391 TI - Continuous Bayesian network for studying the causal links between phosphorus loading and plankton patterns in Lake Simcoe, Ontario, Canada. AB - An ecosystem perspective to restoring beneficial uses in Areas of Concern can be interpreted as a shift from the traditional elucidation of simple cause-effect relationships to a multicausal way of thinking that more effectively accommodates ecosystem complexity. This holistic management paradigm has also pervaded the contemporary ecological modeling practice, making compelling the adoption of more sophisticated ecosystem modeling tools. In this study, our primary objective is to develop a Bayesian hierarchical network of simple ecological models for Lake Simcoe, Ontario, Canada, aiming to establish a realistic representation of the causal connections among exogenous nutrient loading, ambient nutrient conditions, and epilimnetic plankton dynamics. In particular, we used a spatially explicit simple mass-balance model forced with idealized sinusoidal loading to predict total phosphorus concentrations. A structural equation model was then used to delineate the interplay among nutrients, ambient light conditions, phytoplankton, and herbivorous biomass. Our analysis highlights the strength of the causal linkages between total phosphorus and water clarity with phytoplankton as well as the capacity of zooplankton grazing to modulate the algal standing crop. Our Bayesian network is also used to examine the exceedance frequency of threshold values for total phosphorus (15 MUg/L) and chlorophyll a (4 MUg/L) concentrations under scenarios of phosphorus loading reduction. Our study suggests that a 15% phosphorus loading decrease will still result in >25% violations of the 4 MUg chla/L value in the two embayments of Lake Simcoe (Cook's Bay and Kempenfelt Bay). The TP levels will decrease in response to the exogenous loading reductions and this improvement will be primarily manifested in the northcentral segments of the system. PMID- 22676392 TI - Validation of a home-based neurodevelopmental screening tool for under 2-year-old children in Bangladesh. AB - BACKGROUND: Home-based screening to identify young children at risk for neurodevelopmental impairments (NDIs) is needed to guide the targeting of child neurodevelopmental intervention services in Bangladesh. This study aimed to validate such a tool for children under age 2 years. METHODS: A Developmental Screening Questionnaire was administered to mothers of children aged 0-<2 years in an urban community. Inter-rater reliability among the interviewers, who were high school graduates, was determined. All children who were screen positive and a proportion of screen negatives were subsequently assessed for NDIs by professionals. Sensitivity and specificity were calculated by comparing screening with assessment results. RESULTS: Mean kappa coefficient of agreement among interviewers was 0.95. A total of 197 children were screened, of whom 17% screened positive. Fifty-one children, including 24 screen negatives, were assessed for NDIs. Screen-positivity was significantly different between income groups (P = 0.019), and higher in stunted children (odds ratio = 5.76, 95% confidence interval = 1.72-19.28), indicating good discriminant validity Specificity was excellent (84-100%) for all developmental domains. Sensitivity was 100% for vision and hearing; 70% for speech; and 63%, 53%, 48%, and 45% for gross motor, behaviour, fine motor and cognitive impairments, respectively. CONCLUSION: A tool for screening <2-year-old children at risk for NDIs showed high specificity; and was able to identify all children at risk for vision and hearing impairments, nearly three-fourths with speech impairments, two-thirds with gross motor impairments, and about half with behavioural, cognitive and fine motor impairments. The Developmental Screening Questionnaire tool has potential for use by frontline workers to screen large populations and to link to definitive assessment as well as intervention services. PMID- 22676393 TI - Nonionizing radiation as a noninvasive strategy in regenerative medicine: the effect of Ca(2+)-ICR on mouse skeletal muscle cell growth and differentiation. AB - Controlling cell differentiation and proliferation with minimal manipulation is one of the most important goals for cell therapy in clinical applications. In this work, we evaluated the hypothesis that the exposure of myoblast cells (C2C12) to nonionizing radiation (tuned at an extremely low-frequency electromagnetic field at calcium-ion cyclotron frequency of 13.75 Hz) may drive their differentiation toward a myogenic phenotype. C2C12 cells exposed to calcium ion cyclotron resonance (Ca(2+)-ICR) showed a decrease in cellular growth and an increase in the G(0)/G(1) phase. Severe modifications in the shape and morphology and a change in the actin distribution were revealed by the phalloidin fluorescence analysis. A significant upregulation at transcriptional and translational levels of muscle differentiation markers such as myogenin (MYOG), muscle creatine kinase (MCK), and alpha skeletal muscle actin (ASMA) was observed in exposed C2C12 cells. Moreover, the pretreatment with nifedipine (an L-type voltage-gated Ca(2+) channel blocker) led to a reduction of the Ca(2+)-ICR effect. Consequently, it induced a downregulation of the MYOG, MCK, and ASMA mRNA expression affecting adversely the differentiation process. Therefore, our data suggest that Ca(2+)-ICR exposure can upregulate C2C12 differentiation. Although further studies are needed, these results may have important implications in myodegenerative pathology therapies. PMID- 22676394 TI - Short term effects of different omega-3 fatty acid formulation on lipid metabolism in mice fed high or low fat diet. AB - BACKGROUND: Bioactivities of Docosahexaenoic acid (DHA) and Eicosapentaenoic acid (EPA) depend on their chemical forms. The present study was to investigate short term effects of triglyceride (TG), ethyl ester (EE), free fatty acid (FFA) and phospholipid (PL) forms of omega-3 fatty acid (FA) on lipid metabolism in mice, fed high fat or low fat diet. METHOD: Male Balb/c mice were fed with 0.7% different Omega-3 fatty acid formulation: DHA bound free fatty acid (DHA-FFA), DHA bound triglyceride (DHA-TG), DHA bound ethyl ester (DHA-EE) and DHA bound phospholipid (DHA-PL) for 1 week, with dietary fat levels at 5% and 22.5%. Serum and hepatic lipid concentrations were analyzed, as well as the fatty acid composition of liver and brain. RESULT: At low fat level, serum total cholesterol (TC) level in mice fed diets with DHA-FFA, DHA-EE and DHA-PL were significantly lower than that in the control group (P < 0.05). Hepatic TG level decreased significantly in mice fed diets with DHA-TG (P < 0.05), DHA-EE (P < 0.05) and DHA PL (P < 0.05), while TC level in liver was significantly lower in mice fed diets with TG and EE compared with the control group (P < 0.05). At high fat level, mice fed diets with DHA-EE and DHA-PL had significantly lower hepatic TC level compared with the control diet (P < 0.05). Hepatic PL concentration experienced a significant increase in mice fed the diet with PL at high fat level (P < 0.05). Furthermore, both at low and high fat levels, hepatic DHA level significantly increased and AA level significantly decreased in all forms of DHA groups (P < 0.05), compared to control groups at two different fat levels, respectively. Additionally, cerebral DHA level in mice fed diets with DHA-FFA, DHA-EE and DHA PL significantly increased compared with the control at high fat level (P < 0.05), but no significant differences were observed among dietary treatments for mice fed diets with low fat level. CONCLUSION: The present study suggested that not only total dietary fat content but also the molecular forms of omega-3 fatty acids contributed to lipid metabolism in mice. DHA-PL showed effective bioactivity in decreasing hepatic and serum TC, TG levels and increasing omega-3 concentration in liver and brain. PMID- 22676395 TI - Apolipoprotein E genotypes, lipid peroxidation, and antioxidant status among mild and severe preeclamptic women from western Iran: protective role of apolipoprotein epsilon2 allele in severe preeclampsia. AB - OBJECTIVE: The aim of this study was to examine the association of apolipoprotein E (APOE) genotypes and oxidative stress with the risk of mild and severe preeclampsia. METHODS: In a case-control study, 198 women with preeclampsia including 128 women with mild and 70 women with severe preeclampsia and 101 control pregnant women from Western Iran were studied. The APOE genotypes were identified using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The serum level of malondialdehyde (MDA) and total antioxidant capacity (TAC) were determined using high-performance liquid chromatography and commercial kits, respectively. RESULTS: The frequency of APOE epsilon2 allele in severe preeclamptic women (2.1%) was significantly (p = 0.008) lower than that in controls (9.4%). The presence of APOE epsilon2 allele was associated with around five times decreased risk of severe preeclampsia [OR = 0.21 (95% CI = 0.6-0.73, p = 0.014)]. A significantly higher serum level of MDA was observed in women with severe (10.87 +/- 4.61 MUM) and mild (9.81 +/- 3.67 MUM) preeclampsia compared with that in controls. A trend toward decrease serum level of MDA was observed according to the APOE alleles as epsilon2 < epsilon3 < epsilon4 (9.23, 10.22, and 10.43 MUM, respectively). In preeclamptic women, an inverse correlation was detected between serum levels of MDA and HDL-C (r = 0.16, p = 0.029). However, there was a direct correlation between serum level of MDA with diastolic blood pressure (r = 0.15, p = 0.037). CONCLUSION: Our study in a population with Kurdish ethnic background indicates a protective role for APOE epsilon2 allele against severe preeclampsia that might be through high antioxidant capacity of this allele. PMID- 22676396 TI - Development and characterization of attenuated metabolic mutants of Bordetella bronchiseptica for applications in vaccinology. AB - Bordetella bronchiseptica is an important pathogen causing a number of veterinary respiratory syndromes in agriculturally important and food-producing confinement reared animals, resulting in great economic losses annually amounting to billions of euros worldwide. Currently available live vaccines are incompletely satisfactory in terms of efficacy and safety. An efficient vaccine for livestock animals would allow reducing the application of antibiotics, thereby preventing the massive release of pharmaceuticals into the environment. Here, we describe two new potential vaccine strains based on the BB7865 strain. Two independent attenuating mutations were incorporated by homologous recombination in order to make negligible the risk of recombination and subsequent reversion to the virulent phenotype. The mutations are critical for bacterial metabolism, resistance to oxidative stress, intracellular survival and in vivo persistence. The resulting double mutants BB7865 risA aroA and BB7865 risA dapE were characterized as promising vaccine candidates, which are able to confer protection against colonization of the lower respiratory tract after sublethal challenge with the wild-type strain. PMID- 22676397 TI - Safety, tolerability and pharmacokinetics after single and multiple doses of preladenant (SCH420814) administered in healthy subjects. AB - WHAT IS KNOWN AND OBJECTIVE: Preladenant (SCH420814, MK-3814) is a highly selective orally bioavailable non-methylxanthine adenosine 2A (A(2A) ) receptor antagonist under investigation for the treatment for Parkinson's disease. This study evaluated the safety, tolerability and pharmacokinetics of preladenant at single and multiple doses for the first time in humans. METHODS: These were two randomized, double-blind, placebo-controlled, ascending-dose studies, one evaluating single rising preladenant doses (5-200 mg) compared with placebo and the other evaluating multiple rising preladenant doses (10-200 mg once daily over 10 days) compared with placebo. Safety was the primary end point of both studies. Safety evaluations, physical examinations, electrocardiograms, vital signs determinations and routine laboratory tests were performed before and at intervals throughout the studies. Blood samples were collected immediately before study drug administration and at various time points after dosing. Pharmacokinetic assessments of plasma preladenant and metabolites SCH434748 and SCH446637 were performed. RESULTS AND DISCUSSION: One hundred and eight healthy adult men were randomly assigned in a 3 : 1 ratio to receive oral preladenant or matching placebo capsules under fasting conditions. Preladenant reached peak plasma concentrations in ~1 h and then declined rapidly. Dose-related increases in exposure were observed up to 100 mg/day; accumulation was negligible at all doses. Transient mild increases in blood pressure occurred within a few hours after preladenant administration; blood pressure changes were neither cumulative nor dose-related nor associated with clinical sequelae. WHAT IS NEW AND CONCLUSION: Preladenant was generally well tolerated up to the maximum dose tested (200 mg/day). PMID- 22676398 TI - Internet-based aftercare for patients with back pain-a pilot study. AB - OBJECTIVE: In order to maintain treatment gains achieved during multidisciplinary treatments for chronic back pain, patients are challenged to implement the behavioral changes they learned during treatment into their daily life. Offering support during the critical time after treatment conclusion helps patients deal with relapses, provides them with practical advice and social support, and helps to master this transfer. As in-person offerings are not always feasible, innovative concepts are needed to enable hospitals to provide aftercare to their patients. SUBJECTS AND METHODS: An Internet-based aftercare intervention following multidisciplinary therapy for back pain was constructed, implemented, and evaluated. The aftercare program comprised two modules: (1) an individualized self-monitoring module and (2) a weekly, 90-min chat session moderated by a therapist whom participants already knew from treatment. A randomized controlled trial (n=75) was conducted that compared the post-treatment symptom developments of program participants with symptom developments of controls (treatment as usual [TAU]). RESULTS: The program was proven to be feasible and well accepted by participants; on average, 68.2% of the participants rated the previous chat session as helpful. Intention-to-treat analyses demonstrated significant effects on post-treatment courses of disability. The largest effects were found for pain related disability: for TAU participants, disability increased an average of 1.25 scale points (Roland-Morris Questionnaire) per 100 days; for program participants, disability decreased an average of 0.39 scale points (p<0.01). CONCLUSIONS: The aftercare intervention was shown to be feasible and well accepted. Its efficacy should be tested with a larger-scale randomized controlled trial. PMID- 22676399 TI - Interleukin-7-aggravated joint inflammation and tissue destruction in collagen induced arthritis is associated with T-cell and B-cell activation. AB - INTRODUCTION: We sought to investigate the capacity of interleukin (IL)-7 to enhance collagen-induced arthritis and to study by what mechanisms this is achieved. METHODS: Mice received multiple injections with IL-7 or phosphate buffered saline (PBS) as a control. Arthritis severity and incidence were determined by visual examination of the paws. Joint destruction was determined by assessing radiographs and immunohistochemistry of the ankle joints. Total cellularity and numbers of T-cell and B-cell subsets were assessed, as well as ex vivo production of interferon-gamma (IFN-gamma), IL-17, and IL-4. Proinflammatory mediators were measured in serum with multianalyte profiling. RESULTS: IL-7 increased arthritis severity and radiology-assessed joint destruction. This was consistent with IL-7-increased intensity of cell infiltrates, bone erosions, and cartilage damage. Splenic CD19+ B cells and CD19+/GL7+ germinal center B cells, as well as CD4 and CD8 numbers, were increased by IL-7. IL-7 expanded memory T cells, associated with increased percentages of IFN-gamma-, IL-4-, and IL-17 producing CD4+ T cells. On antigen restimulation of draining lymph node cells in vitro IL-7 treatment was found to increase IFN-gamma and IL-17 production, whereas IL-4 was reduced. IL-7 also increased concentrations of proinflammatory mediators, indicative of T-cell activation (sCD40L), vascular activation (VCAM-1, VEGF), tissue destruction (fibroblast growth factor-basic (FGF-b), LIF), and chemotaxis (MIP-1gamma, MIP-3beta, lymphotactin, MDC, and MCP-5). CONCLUSIONS: In arthritic mice, IL-7 causes expansion of T and B cells, associated with increased levels of proinflammatory mediators. IL-7 intensifies arthritis severity and joint destruction, accompanied by increased Th1 and Th17 activity. These data indicate that IL-7 could be an important mediator in arthritic conditions and that targeting IL-7 or its receptor represent novel therapeutic strategies. PMID- 22676400 TI - Comment: Health care provider challenges for reaching Hispanic immigrants with HPV vaccination in rural Georgia. PMID- 22676401 TI - Understanding the interplay of weak forces in [3,3]-sigmatropic rearrangement for stereospecific synthesis of diamines. AB - Chiral diamines are important building blocks for constructing stereoselective catalysts, including transition metal based catalysts and organocatalysts that facilitate oxidation, reduction, hydrolysis, and C-C bond forming reactions. These molecules are also critical components in the synthesis of drugs, including antiviral agents such as Tamiflu and Relenza and anticancer agents such as oxaliplatin and nutlin-3. The diaza-Cope rearrangement reaction provides one of the most versatile methods for rapidly generating a wide variety of chiral diamines stereospecifically and under mild conditions. Weak forces such as hydrogen bonding, electronic, steric, oxyanionic, and conjugation effects can drive this equilibrium process to completion. In this Account, we examine the effect of these individual weak forces on the value of the equilibrium constant for the diaza-Cope rearrangement reaction using both computational and experimental methods. The availability of a wide variety of aldehydes and diamines allows for the facile synthesis of the diimines needed to study the weak forces. Furthermore, because the reaction generally takes place cleanly at ambient temperature, we can easily measure equilibrium constants for rearrangement of the diimines. We use the Hammett equation to further examine the electronic and oxyanionic effects. In addition, computations and experiments provide us with new insights into the origin and extent of stereospecificity for this rearrangement reaction. The diaza-Cope rearrangement, with its unusual interplay between weak forces and the equilibrium constant of the reaction, provides a rare opportunity to study the effects of the fundamental weak forces on a chemical reaction. Among these many weak forces that affect the diaza-Cope rearrangement, the anion effect is the strongest (10.9 kcal/mol) followed by the resonance-assisted hydrogen-bond effect (7.1 kcal/mol), the steric effect (5.7 kcal/mol), the conjugation effect (5.5 kcal/mol), and the electronic effect (3.2 kcal/mol). Based on both computation and experimental data, the effects of these weak forces are additive. Understanding the interplay of the weak forces in the [3,3]-sigmatropic reaction is interesting in its own right and also provides valuable insights for the synthesis of chiral diamine based drugs and catalysts in excellent yield and enantiopurity. PMID- 22676402 TI - Effect of Ti3+ on TiO2-supported Cu catalysts used for CO oxidation. AB - In this paper, we have shown that Cu/TiO(2) catalysts are highly active in CO oxidation. For instance, a 3.4% Cu/TiO(2) catalyst exhibits a higher turnover rate for the effective removal of CO in air than 3-5% Pt/TiO(2) and 20% Cu/ZnO/Al(2)O(3) catalysts. A small amount of Cu(+) species is formed during the calcination treatment at 225 degrees C, which is the main active phase for the CO oxidation. However, it is proposed that some highly dispersed CuO can also form in the TiO(2) lattice during the calcination treatment. Furthermore, a strong electron interaction between Cu(2+) in highly dispersed CuO and Ti(3+) on rutile TiO(2) (Cu(2+)+Ti(3+)->Cu(+)+Ti(4+)) has been shown to occur. Overall, the reduction of Cu(+) is a major factor that contributes to the reaction rate of the CO oxidation. PMID- 22676403 TI - Botulinum neurotoxin: where are we with detection technologies? AB - Because of its high toxicity, botulinum neurotoxin (BoNT) poses a significant risk to humans and it represents a possible biological warfare agent. Nevertheless, BoNT serotypes A and B are considered an effective treatment for a variety of neurological disorders. The growing applicability of BoNT as a drug, and its potential use as a biological threat agent, highlight the urgent need to develop sensitive detection assays and therapeutic counter measures. In the last decade, significant progress has been made in BoNT detection technologies but none have fully replaced the mouse lethality assay, the current "gold standard". Recently, new advances in robotics and the availability of new reagents have allowed development of methods for rapid toxin analysis. These technologies while promising need further refinement. PMID- 22676404 TI - Genetic characterization of Mycobacterium tuberculosis in the West Bank, Palestinian Territories. AB - BACKGROUND: The World Health Organization (WHO) declared human tuberculosis (TB) a global health emergency and launched the "Global Plan to Stop Tuberculosis" which aims to save a million lives by 2015. Global control of TB is increasingly dependent on rapid and accurate genetic typing of species of the Mycobacterium tuberculosis (MTB) complex including M. tuberculosis. The aim of this study was to identify and genetically characterize the MTB isolates circulating in the West Bank, Palestinian Territories. Genotyping of the MTB isolates from patients with pulmonary TB was carried out using two molecular genetic techniques, spoligotyping and mycobacterial interspersed repetitive units-variable number of tandem repeat (MIRU-VNTR) supported by analysis of the MTB specific deletion 1 (TbD1). FINDINGS: A total of 17 MTB patterns were obtained from the 31 clinical isolates analyzed by spoligotyping; corresponding to 2 orphans and 15 shared types (SITs). Fourteen SITs matched a preexisting shared-type in the SITVIT2 database, whereas a single shared-type SIT3348 was newly created. The most common spoligotyping profile was SIT53 (T1 variant), identified in 35.5 % of the TB cases studied. Genetic characterization of 22 clinical isolates via the 15 loci MIRU-VNTR typing distinguished 19 patterns. The 15-loci MIT144 and MIT145 were newly created within this study. Both methods determined the present of M. bovis strains among the isolates. CONCLUSIONS: Significant diversity among the MTB isolates circulating in the West Bank was identified with SIT53-T1 genotype being the most frequent strain. Our results are used as reference database of the strains circulating in our region and may facilitate the implementation of an efficient TB control program. PMID- 22676405 TI - Co-expression analysis identifies CRC and AP1 the regulator of Arabidopsis fatty acid biosynthesis. AB - Fatty acids (FAs) play crucial rules in signal transduction and plant development, however, the regulation of FA metabolism is still poorly understood. To study the relevant regulatory network, fifty-eight FA biosynthesis genes including de novo synthases, desaturases and elongases were selected as "guide genes" to construct the co-expression network. Calculation of the correlation between all Arabidopsis thaliana (L.) genes with each guide gene by Arabidopsis co-expression dating mining tools (ACT) identifies 797 candidate FA-correlated genes. Gene ontology (GO) analysis of these co-expressed genes showed they are tightly correlated to photosynthesis and carbohydrate metabolism, and function in many processes. Interestingly, 63 transcription factors (TFs) were identified as candidate FA biosynthesis regulators and 8 TF families are enriched. Two TF genes, CRC and AP1, both correlating with 8 FA guide genes, were further characterized. Analyses of the ap1 and crc mutant showed the altered total FA composition of mature seeds. The contents of palmitoleic acid, stearic acid, arachidic acid and eicosadienoic acid are decreased, whereas that of oleic acid is increased in ap1 and crc seeds, which is consistent with the qRT-PCR analysis revealing the suppressed expression of the corresponding guide genes. In addition, yeast one-hybrid analysis and electrophoretic mobility shift assay (EMSA) revealed that CRC can bind to the promoter regions of KCS7 and KCS15, indicating that CRC may directly regulate FA biosynthesis. PMID- 22676406 TI - Safety of dilation in adults with eosinophilic esophagitis. AB - Esophageal dilation is an effective therapy for dysphagia in patients with stenosing eosinophilic esophagitis (EoE). Historically, there have been significant concerns of increased perforation rates when dilating EoE patients. More recent studies suggest that improved techniques and increased awareness have decreased complication rates. The aim of this study was to explore the safety of dilation in our population of EoE patients. A retrospective review of all adult EoE patients enrolled in a registry from 2006 to 2010 was performed. All patients who underwent esophageal dilation during this time period were identified and included in the analysis. Our hospital inpatient/outpatient medical records, radiology reports, and endoscopy reports were searched for evidence of any complication following dilation. Perforation, hemorrhage, and hospitalization were identified as a major complication, and chest pain was considered a minor complication. One hundred and ninety-six patients (41 years [12]; mean age [standard deviation], 80% white, 85% male) were identified. In this cohort, 54 patients (28%) underwent 66 total dilations (seven patients underwent two dilations, one patient underwent three dilations, and one patient underwent four dilations). Three dilation techniques were used (Maloney [24], Savary [29] and through-the-scope [13]). There were no major complications encountered. Chest pain was noted in two patients (4%). There were no endoscopic features (rings, furrows, plaques) associated with any complication. Type of dilator, size of dilator, number of prior dilations, and age of patient were also not associated with complications. Endoscopic dilation using a variety of dilators can be safely performed with minimal complications in patients with EoE. PMID- 22676407 TI - Grob fragmentation of 2-azabicyclo[2.2.2]oct-7-ene: tool for the stereoselective synthesis of polysubstituted piperidines. AB - The Grob fragmentation of azabicyclo[2.2.2]octene leads to a dihydropyridinium intermediate. This highly reactive species reacts with a variety of organocuprates and other soft nucleophiles in a regioselective manner, allowing for the rapid and stereoselective synthesis of 2,3,4-trisubstituted 1,2,3,4 tetrahydropyridines. The resulting products were either reduced in situ to the corresponding piperidine or used to achieve the stereoselective construction of various nitrogen heterocycles. PMID- 22676408 TI - Suicide seasonality and antidepressants: a register-based study in Sweden. AB - OBJECTIVE: Seasonality of completed suicides with a peak in spring and early summer is a well-documented finding. The circannual serotonergic functioning is hypothesized to be central in this phenomenon. Antidepressant medications exert their pharmacological action mainly by regulating serotonin. Our aim is to study the amplitude of the seasonal effect among suicide victims positive for different classes of antidepressants or without any antidepressants at the time of death. METHOD: By using Swedish Registers, 12 448 suicides with forensic data for antidepressive medication and information on in-patient-treated mental disorder were identified during 1992-2003. Seasonality was estimated with a Poisson regression variant of the circular normal distribution of completed suicides. RESULTS: Higher suicide seasonality was found for individuals treated with selective serotonin reuptake inhibitor (SSRIs) compared to those with other antidepressant treatment or without any antidepressant treatment. The finding is more evident for men and violent suicide methods and those without history of in patient treatment. CONCLUSION: Our results provide preliminary support for the serotonergic hypothesis of suicide seasonality and raise the question of a possible accentuation of the natural suicide seasonality in patients treated with SSRIs, a hypothesis that warrants further investigation. PMID- 22676409 TI - Telephone referral education, and evidence of retention and transfer after six months. AB - BACKGROUND: Effective communication between clinicians is essential for safe, efficient healthcare. We undertook a study to determine the longer-term effectiveness of an education session employing a structured method to teach referral-making skills to medical students. METHODS: All final year medical students received a forty-five minute education intervention consisting: discussion of effective telephone referrals; video viewing and critique; explanation, demonstration and practice using ISBAR; provision of a memory aid for use in their clinical work. Audio recordings were taken during a subsequent standardised simulation scenario and blindly assessed using a validated scoring system. Recordings were taken immediately before (control), several hours after (intervention), and at approximately six months after the education. Retention of the acronym and self-reports of transfer to the clinical environment were measured with a questionnaire at eight months. RESULTS: Referral clarity at six months was significantly improved from pre-intervention, and referral content showed a trend towards improvement. Both measures were lower than the immediate post-education test. The ISBAR acronym was remembered by 59.4% (n = 95/160) and used by the vast majority of the respondents who had made a clinical telephone referral (n = 135/143; 94.4%). CONCLUSIONS: A brief education session improved telephone communication in a simulated environment above baseline for over six months, achieved functional retention of the acronym over a seven to eight month period and resulted in self reports of transfer of the learning into practice. PMID- 22676410 TI - Carbon isotope fractionation in reactions of 1,2-dibromoethane with FeS and hydrogen sulfide. AB - EDB (1,2-dibromoethane) is frequently detected at sites impacted by leaded gasoline. In reducing environments, EDB is highly susceptible to abiotic degradation. A study was conducted to evaluate the potential of compound-specific isotope analysis (CSIA) in assessing abiotic degradation of EDB in sulfate reducing environments. Water containing EDB was incubated in sealed vials with various combinations of Na(2)S (<0.7 mM) and mackinawite (FeS) (180 mM). Degradation rates in vials containing FeS exceeded those in Na(2)S-only controls. In the presence of FeS, first-order constants ranged from 0.034 +/- 0.002 d(-1) at pH 6 to 0.081 +/- 0.005 d(-1) at pH 8.5. In the presence of FeS, products from reductive debromination (ethylene) and from S(N)2 substitution with S(II) nucleophiles were detected (1,2-dithioethane, DTA). Relatively high yields of DTA suggested that the S(N)2 reactions were not mediated by HS(-) only but likely also included reactions mediated by FeS surface. Significant carbon isotope effects were observed for nucleophilic substitution by HS(-) (epsilon = -31.6 +/- 3.70/00) and for a combination of reductive and substitution pathways in the presence of FeS (-30.9 +/- 0.70/00), indicating good site assessment potential of CSIA. The isotope effects (KIEs) observed in the presence of FeS corroborated the predominance of S(N)2 substitution by nucleophiles combined with two-electron transfer reductive debromination. PMID- 22676411 TI - Correlation among genetic, Euclidean, temporal, and herd ownership distances of porcine reproductive and respiratory syndrome virus strains in Quebec, Canada. AB - BACKGROUND: Porcine reproductive and respiratory syndrome (PRRS) is a viral disease that has a major economic impact for the swine industry. Its control is mostly directed towards preventing its spread which requires a better understanding of the mechanisms of transmission of the virus between herds. The objectives of this study were to describe the genetic diversity and to assess the correlation among genetic, Euclidean and temporal distances and ownership to better understand pathways of transmission. RESULTS: A cross-sectional study was conducted on sites located in a high density area of swine production in Quebec. Geographical coordinates (longitude/latitude), date of submission and ownership were obtained for each site. ORF5 sequencing was attempted on PRRSV positive sites. Proportion of pairwise combinations of strains having >=98% genetic homology were analysed according to Euclidean distances and ownership. Correlations between genetic, Euclidean and temporal distances and ownership were assessed using Mantel tests on continuous and binary matrices. Sensitivity of the correlations between genetic and Euclidean as well as temporal distances was evaluated for different Euclidean and temporal distance thresholds. An ORF5 sequence was identified for 132 of the 176 (75%) PRRSV positive sites; 122 were wild-type strains. The mean (min-max) genetic, Euclidean and temporal pairwise distances were 11.6% (0-18.7), 15.0 km (0.04-45.7) and 218 days (0-852), respectively. Significant positive correlations were observed between genetic and ownership, genetic and Euclidean and between genetic and temporal binary distances. The relationship between genetic and ownership suggests either common sources of animals or semen, employees, technical services or vehicles, whereas that between genetic and Euclidean binary distances is compatible with area spread of the virus. The latter correlation was observed only up to 5 km. CONCLUSIONS: This study suggests that transmission of PRRSV is likely to occur between sites belonging to the same owner or through area spread within a 5 km distance. Both should be considered in the perspective of prevention. PMID- 22676412 TI - Non-solvolytic synthesis of aqueous soluble TiO2 nanoparticles and real-time dynamic measurements of the nanoparticle formation. AB - Highly aqueously dispersible (soluble) TiO2 nanoparticles are usually synthesized by a solution-based sol-gel (solvolysis/condensation) process, and no direct precipitation of titania has been reported. This paper proposes a new approach to synthesize stable TiO2 nanoparticles by a non-solvolytic method - direct liquid phase precipitation at room temperature. Ligand-capped TiO2 nanoparticles are more readily solubilized compared to uncapped TiO2 nanoparticles, and these capped materials show distinct optical absorbance/emission behaviors. The influence of ligands, way of reactant feeding, and post-treatment on the shape, size, crystalline structure, and surface chemistry of the TiO2 nanoparticles has been thoroughly investigated by the combined use of X-ray diffraction, transmission electron microscopy, UV-visible (UV-vis) spectroscopy, and photoluminescence (PL). It is found that all above variables have significant effects on the size, shape, and dispersivity of the final TiO2 nanoparticles. For the first time, real-time UV-vis spectroscopy and PL are used to dynamically detect the formation and growth of TiO2 nanoparticles in solution. These real-time measurements show that the precipitation process begins to nucleate after an initial inhibition period of about 1 h, thereafter a particle growth occurs and reaches the maximum point after 2 h. The synthesis reaction is essentially completed after 4 h. PMID- 22676413 TI - Cytochrome P450-catalyzed degradation of nicotine: fundamental parameters determining hydroxylation by cytochrome P450 2A6 at the 5'-carbon or the n-methyl carbon. AB - The oxidation of (2'S)-nicotine in the active site of human cytochrome P450 2A6 has been subjected to a detailed analysis by theoretical quantum mechanical/molecular mechanical (QM/MM) calculations linked with a theoretical and experimental study of the associated isotope effects. The study has focused on seeking an explanation as to why oxidation at the 5'-carbon position (A) is favored over oxidation at the methyl carbon (CMe) position (B). It is deduced that the choice of hydrogen for abstraction is not determined by geometric features of the active site, but by the lower energy barrier associated with 5' oxidation. N-Demethylation leading to N-hydroxymethylnornicotine requires ca. 6.5 kcal/mol more energy to transfer a hydrogen atom than is required for oxidation on the carbon 5'. Neither protonation of the pyrrolidine nitrogen (N1') nor inclusion of a water molecule in the reaction process influences the balance between the two oxidation pathways. In both cases, the hydrogen transfer step is rate limiting. An analysis of the calculated kinetic isotope effects indicates that the presence of a (2)H in either the C5' or the CMepositions has a significant effect on the reaction kinetics. However, the experimental values of around 2.2-2.6 are considerably lower than those predicted by theoretical calculations (9.3 and 6.9 for C5' or the CMe positions, respectively, in the LS state of Cpd I), typical of the masking commonly found for CYP450 reactions. The fact that similar values are found for cotinine formation from both substrates, however, may indicate that the measured value is not that for H-abstraction but, rather, is a combined value for (2)H influence on electronic redistribution between iminium states of the pyrrolidine ring. This is the first time that oxidation at the C5' or the CMe positions has been directly compared and that isotope effects have been obtained for this reaction in a human cytochrome P450 reaction. PMID- 22676415 TI - Host feeding patterns and preference of Anopheles minimus (Diptera: Culicidae) in a malaria endemic area of western Thailand: baseline site description. AB - BACKGROUND: Host feeding patterns of Anopheles minimus in relation to ambient environmental conditions were observed during a 2-year period at Tum Sua Village, located in Mae Sot District, Tak Province, in western Thailand, where An. minimus is found in abundance and regarded as the most predominant malaria vector species. Detailed information on mosquito behavior is important for understanding the epidemiology of disease transmission and developing more effective and efficient vector control methods. METHODS: Adult mosquitoes were collected every 2 months for two consecutive nights from 1800 to 0600 hrs. Three collection methods were used; indoor human-landing collections (HLC), outdoor HLC, and outdoor cattle-bait collections (CBC). RESULTS: A total of 7,663 female Anopheles mosquitoes were collected of which 5,392 were identified as members of 3 different species complexes, the most prevalent being Anopheles minimus complex (50.36%), followed by Anopheles maculatus complex (19.68%) and Anopheles dirus complex (0.33%). An. minimus s.s. comprised virtually all (> 99.8 percent) of Minimus Complex species captured. Blood feeding behavior of An. minimus was more pronounced during the second half of the evening, showing a slight preference to blood feed outdoors (~60%) versus inside structures. Significantly (P < 0.0001) more An. minimus were collected from human-baited methods compared with a tethered cow, indicating a more anthropophilic feeding behavior. Although a significant difference in total number of mosquitoes from the HLC was recorded between the first and second year, the mean biting frequency over the course of the evening hours remained similar. CONCLUSIONS: The Human landing activity of An. minimus in Tum Sua Village showed a stronger preference/attraction for humans compared to a cow-baited collection method. This study supports the incrimination of An. minimus as the primary malaria vector in the area. A better understanding of mosquito behavior related to host preference, and the temporal and spatial blood feeding activity will help facilitate the design of vector control strategies and effectiveness of vector control management programs in Thailand. PMID- 22676414 TI - Identifying dysregulated pathways in cancers from pathway interaction networks. AB - BACKGROUND: Cancers, a group of multifactorial complex diseases, are generally caused by mutation of multiple genes or dysregulation of pathways. Identifying biomarkers that can characterize cancers would help to understand and diagnose cancers. Traditional computational methods that detect genes differentially expressed between cancer and normal samples fail to work due to small sample size and independent assumption among genes. On the other hand, genes work in concert to perform their functions. Therefore, it is expected that dysregulated pathways will serve as better biomarkers compared with single genes. RESULTS: In this paper, we propose a novel approach to identify dysregulated pathways in cancer based on a pathway interaction network. Our contribution is three-fold. Firstly, we present a new method to construct pathway interaction network based on gene expression, protein-protein interactions and cellular pathways. Secondly, the identification of dysregulated pathways in cancer is treated as a feature selection problem, which is biologically reasonable and easy to interpret. Thirdly, the dysregulated pathways are identified as subnetworks from the pathway interaction networks, where the subnetworks characterize very well the functional dependency or crosstalk between pathways. The benchmarking results on several distinct cancer datasets demonstrate that our method can obtain more reliable and accurate results compared with existing state of the art methods. Further functional analysis and independent literature evidence also confirm that our identified potential pathogenic pathways are biologically reasonable, indicating the effectiveness of our method. CONCLUSIONS: Dysregulated pathways can serve as better biomarkers compared with single genes. In this work, by utilizing pathway interaction networks and gene expression data, we propose a novel approach that effectively identifies dysregulated pathways, which can not only be used as biomarkers to diagnose cancers but also serve as potential drug targets in the future. PMID- 22676416 TI - The cancer stem cell subtype determines immune infiltration of glioblastoma. AB - Immune cell infiltration varies widely between different glioblastomas (GBMs). The underlying mechanism, however, remains unknown. Here we show that TGF-beta regulates proliferation, migration, and tumorigenicity of mesenchymal GBM cancer stem cells (CSCs) in vivo and in vitro. In contrast, proneural GBM CSCs resisted TGF-beta due to TGFR2 deficiency. In vivo, a substantially increased infiltration of immune cells was observed in mesenchymal GBMs, while immune infiltrates were rare in proneural GBMs. On a functional level, proneural CSC lines caused a significantly stronger TGF-beta-dependent suppression of NKG2D expression on CD8(+) T and NK cells in vitro providing a mechanistic explanation for the reduced immune infiltration of proneural GBMs. Thus, the molecular subtype of CSCs TGF-beta-dependently contributes to the degree of immune infiltration. PMID- 22676417 TI - Do Chinese parents with HIV tell their children the truth? A qualitative preliminary study of parental HIV disclosure in China. AB - BACKGROUND: With the extended lifespan of people living with human immunodeficiency virus (HIV) due to the advent of antiretroviral therapy, the disclosure of HIV serostatus to their uninfected children is becoming more critical. However, limited data are available regarding parental HIV disclosure to children in China. We explore patterns of parental HIV disclosure and the reasons for disclosure or non-disclosure to children. METHODS: A preliminary study was conducted using open-ended questions in Guangxi, China in 2011 with 39 parents living with HIV. RESULTS: A majority of participants (77%) had not disclosed their HIV serostatus to their children. Participants who voluntarily disclosed tended to be older and were more likely to disclose to their adult children. Among parents who disclosed, reasons included a need for emotional and financial support, as well as feelings of obligation to their children. Among non disclosing parents, primary reasons included concerns that children were too young to understand, fear of being stigmatized, and fear of increased psychological burden to children. CONCLUSIONS: Few parents with HIV disclosed their HIV status to their children. These data indicate the need for future research to explore disclosure issues in relation to children's age and the implementation of developmentally appropriate interventions and support systems for parents and children affected by HIV in China. PMID- 22676418 TI - Galacto-oligosaccharide synthesis from lactose solution or skim milk using the beta-galactosidase from Bacillus circulans. AB - The synthesis of galacto-oligosaccharides (GOS) catalyzed by a novel commercial preparation of beta-galactosidase from Bacillus circulans (Biolactase) was studied, and the products were characterized by MS and NMR. Using 400 g/L lactose and 1.5 enzyme units per milliliter, the maximum GOS yield, measured by HPAEC-PAD analysis, was 165 g/L (41% w/w of total carbohydrates in the mixture). The major transgalactosylation products were the trisaccharide Gal-beta(1->4)-Gal-beta(1 >4)-Glc and the tetrasaccharide Gal-beta(1->4)-Gal-beta(1->4)-Gal-beta(1->4)-Glc. The GOS yield increased to 198 g/L (49.4% w/w of total carbohydrates) using a higher enzyme concentration (15 U/mL), which minimized the enzyme inactivation under reaction conditions. Using skim milk (with a lactose concentration of 46 g/L), the enzyme also displayed transgalactosylation activity: maximum GOS yield accounted for 15.4% (7.1 g/L), which was obtained at 50% lactose conversion. PMID- 22676419 TI - Vitamin D and the mammary gland: a review on its role in normal development and breast cancer. AB - Breast cancer is a heterogeneous disease associated with diverse biological behaviours and clinical outcome. Although some molecular subgroups of breast cancer have a targeted therapy, the most aggressive tumours still lack a molecular target. Despite vitamin D being classically associated with the physiological role of calcium regulation and phosphate transport in bone metabolism, several studies have demonstrated a wide range of functions for this hormone, which are particularly important in the field of cancer. The mechanisms underlying the protective actions of vitamin D in cancer development are only sparsely understood, but evidence shows that vitamin D participates in cell growth regulation, apoptosis and cell differentiation. In addition, it has been implicated in the suppression of cancer cell invasion, angiogenesis and metastasis. Most of vitamin D biological actions are mediated by the vitamin D receptor and the synthesis and catabolism of this hormone are regulated by the enzymes CYP27B1 and CYP24A1. In the present review we highlight research data concerning the function of this hormone in the mammary gland, with a special focus on breast carcinogenesis. Hence, and although the available data are controversial, we consider not only updated information on the epidemiology of vitamin D in breast cancer and its potential value as a therapeutic agent or prophylactic (with an emphasis on molecular mechanisms and effectors of vitamin D action), but include data on its role in other stages of breast cancer progression as well. Accordingly, we review data on the influence of vitamin D in the development of normal breast and the expression of vitamin D-related proteins (VDR, CYP27B1 and CYP24A21) in benign mammary lesions and ductal carcinomas in situ. PMID- 22676421 TI - Influence of Zeolite on fatty acid composition and egg quality in Tunisian Laying Hens. AB - BACKGROUND: The health benefits of omega-3 and omega-6 polyunsaturated fatty acids (PUFA) are generally recognized. Unfortunately, in most Mediterranean countries, the recommended daily intake of these compounds is rarely met. Therefore, enrichment of commonly occurring foods can boost intake of these fatty acids. In this regard, eggs are an interesting target, as they form an integral part of the diet. RESULT: Zeolite (Clinoptilolites) was added to Laying Hens feed at concentrations 1% or 2% and was evaluated for its effects on performance of the production and on egg quality. The Laying Hens were given access to 110 g of feed mixtures daily that was either a basal diet or a 'zeolite diet' (the basal diet supplemented with clinoptilolite at a level of 1% or 2%). It was found that zeolite treatment had a positive and significatif (p<0.05) effect on some parameters that were measured like egg height and eggshell strength. While dietary zeolite supplementation tended to/or has no significant effects on total egg, eggshell, yolk and albumen weights. It was found also that zeolite mainly increases level of polyunsaturated fatty acids in egg. CONCLUSION: This study showed the significance of using zeolite, as a feed additive for Laying Hens, as part of a comprehensive program to control egg quality and to increase level of polyunsaturated fatty acids on egg. PMID- 22676420 TI - Geographic distance and pH drive bacterial distribution in alkaline lake sediments across Tibetan Plateau. AB - Continent-scale biogeography has been extensively studied in soils and marine systems, but little is known about biogeographical patterns in non-marine sediments. We used barcode pyrosequencing to quantify the effects of local geochemical properties and geographic distance for bacterial community structure and membership, using sediment samples from 15 lakes on the Tibetan Plateau (4 1670 km apart). Bacterial communities were surprisingly diverse, and distinct from soil communities. Four of 26 phyla detected were dominant: Proteobacteria, Bacteroidetes, Firmicutes and Actinobacteria, albeit 20.2% of sequences were unclassified at the phylum level. As previously observed in acidic soil, pH was the dominant factor influencing alkaline sediment community structure, phylotype richness and phylogenetic diversity. In contrast, archaeal communities were less affected by pH. More geographically distant sites had more dissimilar communities (r=0.443, P=0.030). Variance partitioning analysis showed that geographic distance (historical contingencies) contributed more to bacterial community variation (12.2%) than any other factor, although the environmental factors explained more variance when combined (28.9%). Together, our results show that pH is the best predictor of bacterial community structure in alkaline sediments, and confirm that both geographic distance and chemical factors govern bacterial biogeography in lake sediments. PMID- 22676422 TI - Relationships between high-sensitive C-reactive protein and markers of arterial stiffness in hypertensive patients. Differences by sex. AB - BACKGROUND: The present study was designed to evaluate the relationship between high-sensitivity C-reactive protein (hs-CRP) and arterial stiffness according to sex in patients with arterial hypertension. METHODS: A case-series study was carried out in 258 hypertensive patients without antecedents of cardiovascular disease or diabetes mellitus. Nephelometry was used to determine hs-CRP. Office or clinical and home blood pressures were measured with a validated OMRON model M10 sphygmomanometer. Ambulatory blood pressure monitoring was performed with the SpaceLabs 90207 system. Pulse wave velocity (PWV) and central and peripheral augmentation index (AIx) were measured with the SphygmoCor system, and a Sonosite Micromax ultrasound unit was used for automatic measurements of carotid intima media thickness (IMT). Ambulatory arterial stiffness index and home arterial stiffness index were calculated as "1-slope" from the within-person regression analysis of diastolic-on-systolic ambulatory blood pressure. RESULTS: Central and peripheral AIx were greater in women than in men: 35.31 +/- 9.95 vs 26.59 +/- 11.45 and 102.06 +/- 20.47 vs 85.97 +/- 19.13, respectively. IMT was greater in men (0.73 +/- 0.13 vs 0.69 +/- 0.10). hs-CRP was positively correlated to IMT (r=0.261), maximum (r=0.290) and to peripheral AIx (r=0.166) in men, and to PWV in both men (r=0.280) and women (r=0.250). In women, hs-CRP was negatively correlated to central AIx (r= -0.222). For each unit increase in hs-CRP, carotid IMT would increase 0.05 mm in men, and PWV would increase 0.07 m/sec in men and 0.08 m/sec in women, while central AIx would decrease 2.5 units in women. In the multiple linear regression analysis, hs-CRP explained 10.2% and 6.7% of PWV variability in women and men, respectively, 8.4% of carotid IMT variability in men, and 4.9% of central AIx variability in women. CONCLUSIONS: After adjusting for age, other cardiovascular risk factors and the use of antihypertensive and lipid-lowering drugs, hs-CRP was seen to be positively correlated to carotid IMT in men, and negatively correlated to central AIx in women. The association of hs CRP to arterial stiffness parameters differs between men and women. PMID- 22676423 TI - Nanomaterial toxicity testing in the 21st century: use of a predictive toxicological approach and high-throughput screening. AB - The production of engineered nanomaterials (ENMs) is a scientific breakthrough in material design and the development of new consumer products. While the successful implementation of nanotechnology is important for the growth of the global economy, we also need to consider the possible environmental health and safety (EHS) impact as a result of the novel physicochemical properties that could generate hazardous biological outcomes. In order to assess ENM hazard, reliable and reproducible screening approaches are needed to test the basic materials as well as nanoenabled products. A platform is required to investigate the potentially endless number of biophysicochemical interactions at the nano/bio interface, in response to which we have developed a predictive toxicological approach. We define a predictive toxicological approach as the use of mechanisms based high-throughput screening in vitro to make predictions about the physicochemical properties of ENMs that may lead to the generation of pathology or disease outcomes in vivo. The in vivo results are used to validate and improve the in vitro high-throughput screening (HTS) and to establish structure-activity relationships (SARs) that allow hazard ranking and modeling by an appropriate combination of in vitro and in vivo testing. This notion is in agreement with the landmark 2007 report from the US National Academy of Sciences, "Toxicity Testing in the 21st Century: A Vision and a Strategy" (http://www.nap.edu/catalog.php?record_id=11970), which advocates increased efficiency of toxicity testing by transitioning from qualitative, descriptive animal testing to quantitative, mechanistic, and pathway-based toxicity testing in human cells or cell lines using high-throughput approaches. Accordingly, we have implemented HTS approaches to screen compositional and combinatorial ENM libraries to develop hazard ranking and structure-activity relationships that can be used for predicting in vivo injury outcomes. This predictive approach allows the bulk of the screening analysis and high-volume data generation to be carried out in vitro, following which limited, but critical, validation studies are carried out in animals or whole organisms. Risk reduction in the exposed human or environmental populations can then focus on limiting or avoiding exposures that trigger these toxicological responses as well as implementing safer design of potentially hazardous ENMs. In this Account, we review the tools required for establishing predictive toxicology paradigms to assess inhalation and environmental toxicological scenarios through the use of compositional and combinatorial ENM libraries, mechanism-based HTS assays, hazard ranking, and development of nano-SARs. We will discuss the major injury paradigms that have emerged based on specific ENM properties, as well as describing the safer design of ZnO nanoparticles based on characterization of dissolution chemistry as a major predictor of toxicity. PMID- 22676424 TI - Rifampicin has a profound effect on the pharmacokinetics of oral S-ketamine and less on intravenous S-ketamine. AB - Low-dose ketamine is currently used in several acute and chronic pain conditions as an analgesic. Ketamine undergoes extensive metabolism and is thus susceptible to drug-drug interactions. We examined the effect rifampicin, a well-known inducer of many cytochrome P450 (CYP) enzymes and transporters, on the pharmacokinetics of intravenous and oral S-ketamine in healthy volunteers. Eleven healthy volunteers were administered in randomized order 600 mg rifampicin or placebo orally for 6 days in a four-session paired cross-over study. On day 6, S ketamine was administered intravenously (0.1 mg/kg) in the first part of the study and orally (0.3 mg/kg) in the second part. Plasma concentrations of ketamine and norketamine were measured up to 24 hr and behavioural and analgesic effects up to 12 hr. Rifampicin treatment decreased the mean area under the plasma ketamine concentration-time curve extrapolated to infinity (AUC (0 infinity)) of intravenous and oral S-ketamine by 14% (p = 0.005) and 86% (p < 0.001), respectively. Rifampicin decreased greatly the peak plasma concentration of oral S-ketamine by 81% (p < 0.001), but shortened only moderately the elimination half-life of intravenous and oral S-ketamine. Rifampicin decreased the ratio of norketamine AUC (0-infinity) to ketamine AUC (0-infinity) after intravenous S-ketamine by 66%, (p < 0.001) but increased the ratio by 147% (p < 0.001) after the oral administration of S-ketamine. Rifampicin profoundly reduces the plasma concentrations of ketamine and norketamine after oral administration of S-ketamine, by inducing mainly its first-pass metabolism. PMID- 22676425 TI - Communicative functions of GPI-anchored surface proteins in unicellular eukaryotes. AB - Research on several unicellular eukaryotes has identified communicative surface proteins, which are anchored to the outer membrane by glycosylphosphatidylinositol (GPI). Surprisingly, these surface proteins are also released into the environment, raising questions regarding the underlying adaptive advantages and the physical mechanisms that allow for this shedding. This article reviews the current knowledge on several GPI-proteins of different protist species, assembles the puzzling data on the different functions of surface bound and released forms of these proteins, and summarizes their contribution to intra- and interspecific signaling. Recent advances in biochemistry and glycobiology indicate that the GPI-anchor is one of the prerequisites of protein function of membrane bound as well as of released proteins, and hence is a crucial invention for microbial molecular communication. The sensitivity of GPI-anchors (e.g. to phospholipase C) requires consideration of environmental lipase activity of different sources in microbial communities, as these may represent exogenous factors involved in surface protein release. We hypothesize a complex surface protein based communication network and discuss the known facts on protist GPIs in an evolutionary context. PMID- 22676427 TI - Ten-year experience of esophageal self-expanding metal stent insertion at a single institution. AB - Palliation of malignant dysphagia can be achieved using self-expanding metal stents (SEMS). This study was conceived to confirm that the insertion of SEMS improved patient symptoms without serious complications and to allow comparison with recent national data. Retrospective case note review of all patients receiving SEMS over a 10-year period between March 1999 and February 2009 was used in this study. There were 138 consecutive patients (50 female), median age of 75 (range 46-90) years, 122 (88.5%) had primary malignant disease of the esophagus or gastroesophageal junction. In total, 250 endoscopic examinations were carried out, with 200 interventional procedures, including the insertion of 156 SEMS. Before stenting, 74.2% of patients had a dysphagia score of 2-3. Following stent insertion, dysphagia scores improved to 0-1 in 90.3% of patients (P < 0.0001, Wilcoxon signed ranks). No complications were encountered in 61 (44%) patients. Chest pain was the most frequent difficulty, encountered in 50 (36%) patients. Tumor overgrowth occurred in 17 (12.3%) patients and food bolus obstruction was seen in 7% of patients. There were no esophageal perforations attributable to SEMS insertion. Overall 30-day mortality for those with esophago gastric malignancy was 11.6% (16 patients), although the SEMS-related mortality was 2.2% (3 patients). Median survival from SEMS insertion was 3 (IQR 1.5-7) months. Patients requiring re-intervention for tumor overgrowth had a significantly longer median survival of 9.2 months (P= 0.001, log rank). SEMS were well tolerated with overall mortality and complication rates comparable to national data. For the longer survivors, re-intervention for recurrent dysphagia was not unusual. PMID- 22676428 TI - Key functional genes of spermatogenesis identified by microarray analysis. AB - At present many couples face difficulties when trying to conceive that may have a genetic basis. The male factor is the cause of infertility as often as the female. Therefore it is important to identify key genes involved in spermatogenesis which may be linked to male infertility. This review discusses the identification of a range of genes associated with male fertility using microarrays. Based on differences in gene expression profiles between fertile and infertile male subgroups or between fetal and adult male gonads, many genes important for spermatogenesis have been discovered. Genes that are critical at particular stages of spermatogenesis were defined and can be considered as potential male fertility biomarkers. The studies described showed that microarrays may be potentially used as a diagnostic platform to increase the efficacy of diagnosis and perhaps treatment of infertile males. PMID- 22676426 TI - Vulnerability to stress, anxiety and depressive symptoms and metabolic control in type 2 diabetes. AB - BACKGROUND: Vulnerability to stress has been associated to distress, emotional distress symptoms and metabolic control in type 2 diabetes mellitus (T2DM) patients as well. Furthermore some conflicting results were noticed. We aimed to evaluate the effect over metabolic control in what concerns vulnerability to stress beyond depressive and anxiety symptoms. FINDINGS: This cross-sectional study assessed 273 T2DM patients with depressive and anxiety symptoms using the Hospital Anxiety Depression Scale (HADS) and the 23 Questions to assess Vulnerability to Stress (23QVS), along with demographic and clinical diabetes related variables. Hierarchical logistic regression models were used to investigate predictors of poor glycemic control. The results showed an association of depressive symptoms (odds ratio = 1.12, 95%CI = 1.01-1.24, P = 0.030) with increased risk of poor glycemic control. Anxiety symptoms and vulnerability to stress on their own were not predictive of metabolic control, respectively (odds ratio = 0.92, 95%CI = 0.84-1.00, P = 0.187 and odds ratio = 0.98, 95%CI = 0.95-1.01, P = 0.282). CONCLUSIONS: Our data suggested that vulnerability to stress was not predictive of poor glycemic control in T2DM, but depressive symptoms were. PMID- 22676429 TI - Aminomethylene peptide nucleic acid (am-PNA): synthesis, regio-/stereospecific DNA binding, and differential cell uptake of (alpha/gamma,R/S)am-PNA analogues. AB - Inherently chiral, cationic am-PNAs having pendant aminomethylene groups at alpha(R/S) or gamma(S) sites on PNA backbone have been synthesized. The modified PNAs are shown to stabilize duplexes with complementary cDNA in a regio- and stereo-preferred manner with gamma(S)-am PNA superior to alpha(R/S)-am PNAs and alpha(R)-am PNA better than the alpha(S) isomer. The enhanced stabilization of am PNA:DNA duplexes is accompanied by a greater discrimination of mismatched bases. This seems to be a combined result of both electrostatic interactions and conformational preorganization of backbone favoring the cDNA binding. The am-PNAs are demonstrated to effectively traverse the cell membrane, localize in the nucleus of HeLa cells, and exhibit low toxicity to cells. PMID- 22676430 TI - Therapist and client race/ethnicity match: an examination of treatment outcome and process with rural older adults in the deep south. AB - This study investigated the effects of race/ethnicity (r/e) match in cognitive behavioral therapy with rural older adults. Races/ethnicities represented in this study were African-American and White. Treatment followed a CBT treatment protocol and was provided by MSWs to clients in their homes. Results indicated little evidence of differences in outcome and process for matched and non-matched dyads for number of sessions attended, changes in quality of life and psychological symptoms, overall quality of therapy sessions, or the number of sessions considered of unsatisfactory quality. Our findings are consistent with recent research on r/e matching and extend these findings to a sample of rural older adults. PMID- 22676431 TI - Diastolic function in pregnant patients with cardiac symptoms. AB - OBJECTIVE: Dyspnea on exertion and peripheral edema occur routinely during normal gestational stage, making early diagnosis of congestive heart failure (CHF) during pregnancy difficult. Abnormal left ventricular (LV) diastolic function may be associated with dyspnea on exertion and peripheral edema, and brain natriuretic peptide (BNP) correlates with volume overload in nonpregnant populations. We tested the hypothesis that abnormal echocardiographic diastolic parameters and elevated BNP correlate in symptomatic pregnant patients. METHODS: Sixty-six gravidas presented to an Obstetric Cardiology Clinic were analyzed. Data including symptoms of CHF, BNP, and maternal and gestational ages were recorded. Echocardiograms were reviewed to measure the diastolic parameters E, A, e', and a' wave velocities and left atrial volume index (LAVI). Logistic regression was performed to characterize the relationship between diastolic parameters and BNP. RESULTS: Among the 66 pregnant patients included in the analysis, only 6 were found to have significant LV systolic dysfunction. LAVI, E, and E/e' ratio correlated positively with BNP in this symptomatic population (p = 0.008, 0.007, and 0.002, respectively). CONCLUSIONS: Abnormal diastolic parameters that represent increased LV filling pressures correlated with higher BNP levels in pregnant patients with symptoms of CHF. This suggests that symptoms may be due to diastolic dysfunction, and BNP levels may identify elevated LV filling pressures in symptomatic pregnant patients. PMID- 22676432 TI - A multidimensional perspective of the mental health of preclinical medical students. AB - Previous research on medical students' mental health has focused almost exclusively on students' emotional well-being and/or their personal psychological functioning, neglecting the more public side of medical training - the students' social health. A total of 237 preclinical students completed surveys at the beginning and the end of their academic year assessing their emotional, psychological, and social well-being, respectively, as well as the overall negative impact medical school stressors had on their lives. Although first and second year students were found to significantly decrease in emotional well being, first year students were found to increase in social well-being, with further analysis showing an increase among first year students specifically in the feelings of social integration and social acceptance. The overall negative impact from the stressors was found to predict the change in emotional well being, but not other dimensions of well-being. However, the negative impact from stressors was also found to indirectly impact students' emotional well-being through negatively affecting their psychological and social well-being. The authors present the value in measuring medical students' well-being from a multidimensional perspective as well as highlight the potential "condensing" of students' social world as early as their first year of training. Recommendations are made that researchers continue to focus on the promotion and protection of students' positive mental health in the preliminary stages of medical education, as well as endorse programs that cultivate the benefits of solidarity and integration experienced by first year students. PMID- 22676433 TI - Sorption of four hydrophobic organic compounds by three chemically distinct polymers: role of chemical and physical composition. AB - The sorption behavior of four hydrophobic organic contaminants (HOCs) (i.e., phenanthrene, naphthalene, lindane, and 1-naphthol) by three types of polymers namely polyethylene (PE), polystyrene (PS), and polyphenyleneoxide (PPO) was examined in this work. The organic carbon content-normalized sorption coefficients (K(oc)) of phenanthrene, lindane, and naphthalene by PEs of same composition but distinct physical makeup of domains increased with their crystallinity reduction (from 58.7 to 25.5%), suggesting that mobility and abundance of rubbery domains in polymers regulated HOC sorption. Cross-linking in styrene-divinylbenzene copolymer (PS2) created substantial surface area and porosity, thus, K(oc) values of phenanthrene, lindane, naphthalene, and 1 naphthol by PS2 were as high as 274.8, 212.3, 27.4, and 1.5 times of those by the linear polystyrene (PS1). The K(oc) values of lindane, naphthalene, and 1 naphthol by polar PPO were approximately 1-3 orders of magnitude higher than those by PS1, and PPO had comparable sorption for phenanthrene but higher sorption for naphthalene and 1-naphthol than PS2. This can be a result that a portion of O-containing moieties in PPO were masked in the interior part, while leaving the hydrophobic domains exposed outside, therefore demonstrating the great influence of the spatial arrangement of domains in polymers on HOC sorption. PMID- 22676434 TI - First isolation and characterization of Chryseobacterium shigense from rainbow trout. AB - BACKGROUND: There have been an increasing number of infections in fish associated with different species of Chryseobacterium, being considered potentially emerging pathogens. Nevertheless the knowledge of the diversity of species associated with fish disease is partial due to the problems for a correct identification at the species level based exclusively on phenotypic laboratory methods. RESULTS: Chryseobacterium shigense was isolated from the liver, kidney and gills of diseased rainbow trout in different disease episodes that occurred in a fish farm between May 2008 and June 2009. Identity of the isolates was confirmed by 16 S rRNA gene sequencing and phenotypic characterization. Isolates represented a single strain as determined by random amplified polymorphic DNA analysis. CONCLUSIONS: This is the first description of the recovery of C. shigense from clinical specimens in trout, a very different habitat to fresh lactic acid beverage where it was initially isolated. PMID- 22676436 TI - The language of gene ontology: a Zipf's law analysis. AB - BACKGROUND: Most major genome projects and sequence databases provide a GO annotation of their data, either automatically or through human annotators, creating a large corpus of data written in the language of GO. Texts written in natural language show a statistical power law behaviour, Zipf's law, the exponent of which can provide useful information on the nature of the language being used. We have therefore explored the hypothesis that collections of GO annotations will show similar statistical behaviours to natural language. RESULTS: Annotations from the Gene Ontology Annotation project were found to follow Zipf's law. Surprisingly, the measured power law exponents were consistently different between annotation captured using the three GO sub-ontologies in the corpora (function, process and component). On filtering the corpora using GO evidence codes we found that the value of the measured power law exponent responded in a predictable way as a function of the evidence codes used to support the annotation. CONCLUSIONS: Techniques from computational linguistics can provide new insights into the annotation process. GO annotations show similar statistical behaviours to those seen in natural language with measured exponents that provide a signal which correlates with the nature of the evidence codes used to support the annotations, suggesting that the measured exponent might provide a signal regarding the information content of the annotation. PMID- 22676435 TI - New quality regulations versus established nursing home practice: a qualitative study. AB - BACKGROUND: Western governments have initiated reforms to improve the quality of care for nursing home residents. Most of these reforms encompass the use of regulations and national quality indicators. In the Norwegian context, these regulations comprise two pages of text that are easy to read and understand. They focus particularly on residents' rights to plan their day-to-day life in nursing homes. However, the research literature indicates that the implementation of the new regulations, particularly if they aim to change nursing practice, is extremely challenging. The aim of this study was to further explore and describe nursing practice to gain a deeper understanding of why it is so hard to implement the new regulations. METHODS: For this qualitative study, an ethnographic design was chosen to explore and describe nursing practice. Fieldwork was conducted in two nursing homes. In total, 45 nurses and nursing aides were included in participant observation, and 10 were interviewed at the end of the field study. RESULTS: Findings indicate that the staff knew little about the new quality regulations, and that the quality of their work was guided by other factors rooted in their nursing practice. Further analyses revealed that the staff appeared to be committed to daily routines and also that they always seemed to know what to do. Having routines and always knowing what to do mutually strengthen and enhance each other, and together they form a powerful force that makes daily nursing care a taken-for-granted activity. CONCLUSION: New regulations are challenging to implement because nursing practices are so strongly embedded. Improving practice requires systematic and deeply rooted practical change in everyday action and thinking. PMID- 22676437 TI - Detection of alkaline phosphatase in canine cells previously stained with Wright Giemsa and its utility in differentiating osteosarcoma from other mesenchymal tumors. AB - BACKGROUND: Osteosarcoma (OSA) is a common primary bone tumor in dogs. Demonstration of alkaline phosphatase (ALP) reactivity by tumor cells on unstained slides is useful in differentiating osteosarcoma from other types of sarcoma. However, unstained slides are not always available. OBJECTIVES: The objectives of this study were to evaluate the diagnostic utility of detecting ALP expression in differentiating osteosarcoma from other sarcomas in dogs using cytologic material previously stained with Wright-Giemsa stain and to assess the sensitivity and specificity of ALP expression for diagnosing osteosarcoma using a specific protocol. METHODS: Archived aspirates of histologically confirmed sarcomas in dogs that had been previously stained with Wright-Giemsa stain were treated with 5-bromo, 4-chloro, 3-indolyl phosphate/nitroblue tetrazolium (BCIP/NBT) as a substrate for ALP. Cells were evaluated for expression of ALP after incubation with BCIP/NBT for 1 hour. Sensitivity and specificity of ALP expression for diagnosis of OSA were calculated. RESULTS: In samples from 83 dogs, cells from 15/17 OSAs and from 4/66 tumors other than OSA (amelanotic melanoma, gastrointestinal stromal tumor, collision tumor, and anaplastic sarcoma) expressed ALP. Sensitivity and specificity of ALP expression detected using BCIP/NBT substrate applied to cells previously stained with Wright-Giemsa stain for OSA were 88 and 94%, respectively. CONCLUSIONS: ALP expression detected using BCIP/NBT substrate applied to previously stained cells is useful in differentiating canine OSA from other mesenchymal neoplasms. PMID- 22676438 TI - The effectiveness of self-care support interventions for children and young people with long-term conditions: a systematic review. AB - Children's health policy has highlighted the need to develop self-care programmes. However, there is a lack of evidence on which to base the development of such programmes. This paper reviews the published research on the effectiveness of self-care support interventions for children and young people with asthma, cystic fibrosis and diabetes. A systematic search was conducted of a range of electronic databases, supplemented by searching the reference lists of retrieved papers and published reviews. Retrieved studies were assessed against quality and eligibility criteria by two independent reviewers. The results were narratively synthesized to examine the effectiveness of self-care support interventions on health status, psycho-social well-being, condition-related knowledge, health service use and participant satisfaction. The search strategy identified 4261 papers which were screened against the review inclusion criteria. A total of 194 papers were assessed as being potentially eligible for inclusion with 15 papers being judged as adequate to include in the review. There is strong evidence of the effectiveness of interventions that target children/young people; use e-health or group-based methods; that are delivered in community settings. There is no evidence that interventions that focus on parents alone or are delivered only in hospital settings are effective. While there is some evidence to inform the development of self-care support programmes, there is a need for well-designed trials of interventions that are feasible to transfer into real life settings and which involve parents and children in their development. PMID- 22676440 TI - Application of anodized titanium for enhanced recruitment of endothelial progenitor cells. AB - OBJECTIVES: To study the efficacy of an effective anodized titanium surface with enhanced attachment of endothelial progenitor cell (EPC). BACKGROUND: In-stent restenosis is a major obstacle for vascular patency after catheter-based intravascular interventions. Recently, stents that capture EPCs have been paid attention in order to make a functional endothelialized layer at the site of stent-induced endothelial denudation. Anodized titanium has been shown to enhance stem cell attachment. Anodization is a quick and inexpensive method, which can provide suitable stent surface. METHODS: Surface topography was examined by high resolution scanning electron microscopy (SEM). Substrates were co-cultured with EPCs at second passage in 24-well culture plates. Evaluation of cell growth, proliferation, viability, surface cytotoxicity and cell adhesion was performed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test and 4,6-diamidino-2-phenylindole dihydrochloride staining. For platelet attachment, platelets added to substrates were evaluated under SEM. RESULTS: The average MTT values for tissue culture polystyrene plate, unanodized and anodized titanium with nanostructure were equal to 0.49, 0.16 and 0.72, respectively (P < 0.05). The surface had no cytotoxic effects on cells. The average cell attachment results showed that 9,955 +/- 461.18, 3,300 +/- 197.98 and 11,359 +/- 458.10 EPCs were attached per well of tissue culture polystyrene plate, unanodized and anodized titanium surfaces, respectively (P < 0.05). CONCLUSIONS: Anodized titanium surfaces can be potentially applied for devices that need enhanced recruitment of EPCs. This unique property makes these anodized surfaces good and cheap candidates for designing cardiovascular medical devices as endovascular stents. PMID- 22676439 TI - Successful management of unruptured interstitial pregnancy in 17 consecutive cases by using laparoscopic surgery. AB - AIMS: To analyse the optimal laparoscopic surgical techniques for the treatment of interstitial pregnancy to minimise bleeding during the operative procedure and the safety of the subsequent pregnancy. METHODS: Advanced bipolar coagulator was used to achieve haemostasis. RESULTS: The mean gestational age was 55 +/- 5.1 days. All 17 women with an interstitial pregnancy were successfully treated by laparoscopic surgery without any complication. No surgery was converted to laparotomy. The mean pre-operative beta-human chorionic gonadotropin (beta-hCG) serum concentration was 14 696 +/- 11 705 mIU/mL. This value decreased to 1911 +/ 1769 mIU/mL at 3-day post-operation. Among women who underwent laparoscopic surgery, a cornual resection was performed in 16 (94.1%) cases. One (5.8%) woman underwent a laparoscopic evacuation of the conceptus and received a local injection of 10 mg methotrexate. The volume of blood loss was <25 mL in 16 cases. However, one woman experienced a rupture at the beginning of the operation and lost 250 mL of blood. The mean hospital stay was 4.5 days. Four of the nine women who chose to retain their reproductive function had subsequent normal pregnancies, but all received an elective caesarean delivery prior to labour. CONCLUSIONS: The laparoscopic management of women with unruptured interstitial pregnancy can frequently be performed without haemorrhage or complication using advanced bipolar coagulation. The small sample of successful subsequent pregnancies demonstrates the safety and effectiveness of this technique, but this finding should be confirmed by further investigations. PMID- 22676441 TI - Study on a new synthesis approach of glyphosate. AB - On the basis of glycine-dimethyl phosphite synthesis of glyphosate, a new synthesis approach of glyphosate, without using triethylamine and the establishment of triethylamine recovery equipment, was designed in the laboratory. The environmental pollutants were reduced. The influences of reactant amount (mol), reaction temperature ( degrees C), and reaction time (min) on the glyphosate yield and purity were investigated. The results showed that the glyphosate yield and purity could be 80.12 and 86.31 wt %, respectively, under the optimum scheme for glyphosate yield (glycine consumption, 0.1 mol; dimethyl phosphite consumption, 0.12 mol; condensation reaction temperature, 50 degrees C; hydrochloric acid consumption in hydrolysis reaction, 0.35 mol; temperature of acidification with hydrochloric acid, 10 degrees C; adjusting hydrolysis product pH value, 1.0; time of dropping esterifying liquid into hydrochloric acid in hydrolysis reaction, 80 min; hydrolysis reaction temperature, 120 degrees C; and vacuum distillation time, 90 min), and the glyphosate yield and purity could be 77.92 and 94.94 wt %, respectively, under the optimum scheme for glyphosate purity (glycine consumption, 0.1 mol; dimethyl phosphite consumption, 0.1 mol; condensation reaction temperature, 50 degrees C; hydrochloric acid consumption in hydrolysis reaction, 0.35 mol; temperature of acidification with hydrochloric acid, 10 degrees C; adjusting hydrolysis product pH value, 1.5; time of dropping esterifying liquid into hydrochloric acid in hydrolysis reaction, 60 min; hydrolysis reaction temperature, 110 degrees C; and vacuum distillation time, 90 min). The product structures under the two schemes were confirmed by means of FTIR (Fourier transform infrared spectroscopy) and (1)H NMR ((1)H nuclear magnetic resonance spectroscopy). PMID- 22676442 TI - Influence of cyclic dimer formation on the phase behavior of carboxylic acids. AB - A new thermodynamic approach based on the Sear and Jackson association theory for doubly bonded dimers [Mol. Phys.1994, 82, 1033] is proposed to describe the thermodynamic properties of carboxylic acids. The new model is able to simultaneously represent the vapor pressures, saturated densities, and vaporization enthalpies of the shortest acids and is in a much better agreement with experimental data than other approaches that do no consider the formation of cyclic dimers. The new model is applied to mixtures of carboxylic acids with nonassociating compounds, and a very good description of the vapor-liquid equilibria in mixtures of alkanes + carboxylic acids is obtained. PMID- 22676444 TI - A new diagnostic technique for tinea incognito: in vivo reflectance confocal microscopy. Report of five cases. AB - BACKGROUND/PURPOSE: In vivo confocal laser scanning microscopy (CLSM) is a modern non-invasive method for investigation of the skin that allows real-time visualization of individual cells and subcellular structures with the highest resolution imaging comparable to the routine histopathology. Our aim was to demonstrate the potential of CLSM for non-invasive diagnosis of difficult tinea incognito cases. METHODS: Clinically atypical lesions in five cases of tinea incognito due to dermatophyte spp. were demonstrated using reflectance confocal laser scanning microscopy (RCM), parallel to KOH preparation and fungal culture of skin scrapings performed in the same patients. RESULTS: The morphological features characteristic for tinea incognito, namely linear branched hyphae in the intercellular area of the stratum corneum, were readily detectable by means of CLSM. In vivo tissue imaging were performed at three different wavelengths (785, 658, 445 nm) and the best images of fungal elements were obtained at 445 nm. All of our five cases had similar reflectance confocal microscopical findings. CONCLUSIONS: Our findings suggest the potential of CLSM as a non-invasive tool for the diagnosis of tinea incognito having atypical clinical appearance. Although at present the reflectance confocal microscopy cannot replace the current diagnostic standards for tinea incognito, it may be successfully used as in vivo non-invasive screening tool to facilitate the diagnosis and point to the need for further investigation of the patient. PMID- 22676443 TI - Transfected MDCK cell line with enhanced expression of CYP3A4 and P-glycoprotein as a model to study their role in drug transport and metabolism. AB - The aim of this study was to characterize and utilize MDCK cell line expressing CYP3A4 and P-glycoprotein as an in vitro model for evaluating drug-herb and drug drug of abuse interactions. MDCK cell line simultaneously expressing P-gp and CYP3A4 (MMC) was developed and characterized by using expression and activity studies. Cellular transport study of 200 MUM cortisol was performed to determine their combined activity. The study was carried across MDCK-WT, MDCK-MDR1 and MMC cell lines. Similar studies were also carried out in the presence of 50 MUM naringin and 3 MUM morphine. Samples were analyzed by HPLC for drug and its CYP3A4 metabolite. PCR, qPCR and Western blot studies confirmed the enhanced expression of the proteins in the transfected cells. The Vivid CYP3A4 assay and ketoconazole inhibition studies further confirmed the presence of active protein. Apical to basal transport of cortisol was found to be 10- and 3-fold lower in MMC as compared to MDCK-WT and MDCK-MDR1 respectively. Higher amount of metabolite was formed in MMC than in MDCK-WT, indicating enhanced expression of CYP3A4. Highest cortisol metabolite formation was observed in MMC cell line due to the combined activities of CYP3A4 and P-gp. Transport of cortisol increased 5-fold in the presence of naringin in MMC and doubled in MDCK-MDR1. Cortisol transport in MMC was significantly lower than that in MDCK-WT in the presence of naringin. The permeability increased 3-fold in the presence of morphine, which is a weaker inhibitor of CYP3A4. Formation of 6beta-hydroxy cortisol was found to decrease in the presence of morphine and naringin. This new model cell line with its enhanced CYP3A4 and P-gp levels in addition to short culture time can serve as an invaluable model to study drug-drug interactions. This cell line can also be used to study the combined contribution of efflux transporter and metabolizing enzymes toward drug-drug interactions. PMID- 22676445 TI - High prevalence of human papillomavirus in esophageal squamous cell carcinoma: a study in paired samples. AB - Esophageal squamous cell carcinoma (ESCC) is one of the common cancers with a poor prognosis. Incidences of human papillomavirus (HPV) infection range from 0 to 67% in different parts of the world. It has been frequently associated with high-risk HPV genotypes 16 and 18. The present study analyzes the prevalence of HPV infection in ESCC tumor and adjoining mucosa. Fresh tissue samples were obtained from ESCC tumor (group I) and adjoining mucosa (group II). Aliquots of DNA extracts were used. There were 23 patients with paired samples, 19 (83%) were male. HPV was positive in 20/23 (87%). Mean age of HPV positive in group I was 56.63 +/- 6.96 and in group II 54.31 +/- 7.13 years (P > 0.05). Majority had more than one viral type. HPV52 was the most common observed in 14 (61%) males and two (9%) females. Other common viruses were HPV55, 39, and 59. Smoking had a significant association with viral positivity. p63 and p16 oncoproteins correlated with degree of tumor differentiation but not with viral status. We documented high prevalence of high-risk HPV in ESCC. Our observations support the concept of persistent infection by an oncogenic HPV in cancer development. Our study highlights importance of documenting viral genotype in a defined geographic area. PMID- 22676446 TI - Chronic care management in Danish general practice--a cross-sectional study of workload and multimorbidity. AB - BACKGROUND: About 30% of the Danish population has one or more chronic conditions, and general practitioners (GPs) play a key role in effective chronic care management. However, little is known about these encounters in general practice. The aim was to describe the frequency of patients with one or more chronic conditions in general practice and how these consultations were experienced by the GPs. METHODS: All GPs in the Central Denmark Region were invited to register all contacts during one day in the 12-month study period from December; 404 (46%) accepted. For each patient contact, the GPs were asked to fill in a one-page registration form covering information on chronic disease, reason for encounter, diagnosis, number of additional psychosocial problems raised by the patient during the consultation, time consumption, experienced burden of the consultation, referral to specialized care, and whether a nurse could have substituted the GP. Patients were categorized according to the number of chronic conditions (none, one, two, three or more) and the categories compared with regard to the GP-experienced burden of the contacts. Moreover, we examined which chronic conditions posed the the greatest challenge to the GPs. RESULTS: Patients aged 40 years or more had a total of 8,236 contacts. Among these patients 2,849 (34.6%; 95% CI 33.6-35.6) had one and 2,596 (31.5%; CI 30.5-32.5) had more than one chronic disease. The time consumption and the burden of their contacts tended to rise with the number of chronic conditions. Being present in 22.9% (CI 21.6-24.3) of all face-to-face contacts, hypertension was the most common chronic condition. The burden of the contacts was experienced as particularly heavy for patients with depression and dementia due to more additional psychosocial problems and the time consumption. CONCLUSION: General practitioners considered consultations with multimorbid patients demanding and not easily delegated to nurses. As the number of patients with chronic conditions and multimorbidity is increasing, GPs can be expected to face a heavier workload in the future. PMID- 22676447 TI - Sexual communication and condom use among Chinese men who have sex with men in Beijing. AB - This study collected cross-sectional data from 307 young Chinese men who have sex with men (MSM) to explore the characteristics of sexual communications, including target of communication (stable partners, casual partners), topics of communication (condom use, HIV/STDs prevention, and sexual history), and the associations between sexual communication characteristics and condom use. A variety of measures were employed to assess respondents' condom use with different sexual partners over different recall periods. Chi-square tests were employed to examine the relationships between sexual communication characteristics and condom use. This study found that sexual communications with regular partners about topics, such as condom use, HIV/STDs prevention, and current and past sexual relationship were associated with condom use with regular partners. Respondents who had sexual communications with both regular and casual partners were more likely to use condoms with their regular partners. The findings in the current study provided empirical evidence for the importance of frequent sexual communication between Chinese MSM and their sex partners. PMID- 22676448 TI - Cryopreservation of cell/scaffold tissue-engineered constructs. AB - The aim of this work was to study the effect of cryopreservation over the functionality of tissue-engineered constructs, analyzing the survival and viability of cells seeded, cultured, and cryopreserved onto 3D scaffolds. Further, it also evaluated the effect of cryopreservation over the properties of the scaffold material itself since these are critical for the engineering of most tissues and in particular, tissues such as bone. For this purpose, porous scaffolds, namely fiber meshes based on a starch and poly(caprolactone) blend were seeded with goat bone marrow stem cells (GBMSCs) and cryopreserved for 7 days. Discs of the same material seeded with GBMSCs were also used as controls. After this period, these samples were analyzed and compared to samples collected before the cryopreservation process. The obtained results demonstrate that it is possible to maintain cell viability and scaffolds properties upon cryopreservation of tissue-engineered constructs based on starch scaffolds and goat bone marrow mesenchymal cells using standard cryopreservation methods. In addition, the outcomes of this study suggest that the greater porosity and interconnectivity of scaffolds favor the retention of cellular content and cellular viability during cryopreservation processes, when compared with nonporous discs. These findings indicate that it might be possible to prepare off the-shelf engineered tissue substitutes and preserve them to be immediately available upon request for patients' needs. PMID- 22676449 TI - Areca nut chewing and systemic inflammation: evidence of a common pathway for systemic diseases. AB - BACKGROUND: Areca nut, the seed of fruit of an oriental palm, known as Areca catechu, is commonly chewed in many countries. Diabetes, hypertension, cardiovascular diseases, oropharyngeal and oesophageal cancers have been associated with areca nut chewing and the mechanism by which areca nut chewing increases the risk of systemic diseases remains elusive. We hypothesize that systemic inflammation may be elevated among areca nut users, which is linked with many systemic diseases. Therefore, this present study was conducted to examine the systemic inflammation among areca nut chewers and healthy controls. METHODS: This was an observational cross sectional study carried out on areca nut chewers and healthy individuals in Karachi, Pakistan. Participants were selected from a region of the city by invitation request sent from door to door. Information was collected regarding the socio-demographic profile and the pattern of use, and a blood sample was obtained to measure the level of C-reactive protein (CRP). We carried out multiple logistic regressions to investigate the association between socio-demographic profile, areca nut chewing and CRP levels. RESULTS: We carried out final analysis on 1112 individuals of which 556 were areca nut chewers and 556 were the age, gender and area matched controls. Areca nut chewers had a significantly higher proportion of men (15.1%, n = 84) who had an elevated CRP (>10 mg/dl) as compared to controls (5.2%, n = 29). Multivariate analyses showed that areca nut chewers had significantly higher odds of an elevated CRP (OR = 3.23, 95% CI 2.08-5.02, p value <0.001) as compared to controls. Increase in amount of areca nut consumption had a significant dose-response relationship with systemic inflammation (p for trend <0.001). Further analysis revealed that areca nut chewers with tobacco additives were two times more likely to have an elevated CRP as compared to raw areca nut users. These associations remained unchanged after adjustments for age, BMI and years of full time education. CONCLUSIONS: Areca nut chewing has a significant association with systemic inflammation. Further work is required to confirm that systemic inflammation is the main pathway by which areca nut use increases the risk of systemic diseases. PMID- 22676452 TI - Vascular smooth muscle cells initiate proliferation of mesenchymal stem cells by mitochondrial transfer via tunneling nanotubes. AB - Multipotent mesenchymal stem cells (MSCs) are promising candidates for regenerative cell-based therapy. The mechanisms underlying MSC differentiation and other functions relevant to therapeutic avenues remain however a matter of debate. Recent reports imply a critical role for intercellular contacts in MSC differentiation. We studied MSC differentiation to vascular smooth muscle cells (VSMCs) in a coculture model using human primary MSCs and VSMCs. We observed that under these conditions, MSCs did not undergo the expected differentiation process. Instead, they revealed an increased proliferation rate. The upregulated MSC proliferation was initiated by direct contacts of MSCs with VSMCs; indirect coculture of both cell types in transwells was ineffective. Intercellular contacts affected cell growth in a unidirectional fashion, since VSMC proliferation was not changed. We observed formation of so-called tunneling nanotubes (TNTs) between MSCs and VSMCs that revealed an intercellular exchange of a fluorescent cell tracker dye. Disruption of TNTs using cytochalasin D or latrunculin B abolished increased proliferation of MSCs initiated by contacts with VSMCs. Using specific fluorescent markers, we identified exchange of mitochondria via TNTs. By generation of VSMCs with mitochondrial dysfunction, we show that mitochondrial transfer from VSMCs to MSCs was required to regulate MSC proliferation in coculture. Our data suggest that MSC interaction with other cell types does not necessarily result in the differentiation process, but rather may initiate a proliferative response. They further point to complex machinery of intercellular communications at the place of vascular injury and to an unrecognized role of mitochondria in these processes. PMID- 22676453 TI - Surface evolution of the deepwater horizon oil spill patch: combined effects of circulation and wind-induced drift. AB - Following the Deepwater Horizon blowout, major concerns were raised about the probability that the Loop Current would entrain oil at the surface of the Gulf of Mexico toward South Florida. However, such a scenario did not materialize. Results from a modeling approach suggest that the prevailing winds, through the drift they induced at the ocean surface, played a major role in pushing the oil toward the coasts along the northern Gulf, and, in synergy with the Loop Current evolution, prevented the oil from reaching the Florida Straits. This implies that both oceanic currents and surface wind-induced drift must be taken into account for the successful forecasting of the trajectories and landfall of oil particles, even in energetic environments such as the Gulf of Mexico. Consequently, the time range of these predictions is limited to the weather forecasting range, in addition to the range set up by ocean forecasting capabilities. PMID- 22676454 TI - Visible light-induced synthesis of 3,4-diarylthiophenes from 3,4-diaryl-2,5 dihydrothiophenes. AB - Using a catalytic amount of platinum(II) terpyridyl complex 3, 3,4 diarylthiophenes (2a-f) could be synthesized from 3,4-diaryl-2,5 dihydrothiophenes (1a-f) under visible light (lambda > 450 nm) irradiation in degassed CH(3)CN. Spectroscopic study and product analysis reveal that the reaction is initiated by photoinduced electron transfer from 3,4-diaryl-2,5 dihydrothiophenes to platinum(II) complex 3, leading to the formation of 3,4 diarylthiophenes. PMID- 22676455 TI - Integrated optimization of fish oil microencapsulation process by spray drying. AB - An integrated approach through coupling response surface method (RSM) and genetic algorithm (GA) was applied to optimize the spray dryer operational condition for production of fish oil microcapsules. The inlet drying air temperature, aspirator rate, and peristaltic pump rate were independent and encapsulation efficiency (EE) and exergy efficiency were dependent variables. RSM was applied to establish the relationship between the independent and dependent variables followed by integrating the developed models using three mathematical approaches and measure the fitness value of GA. Consequently, the optimal drying condition for microencapsulation of fish oil was: inlet drying air temperature = 177.23 degrees C, aspirator rate = 63.93%, and peristaltic pump rate = 14.04% yielding exergy efficiency of 8.10% and EE of 79.14%. The results of confirmation experiments for selected drying condition proved the capability of utilized approach for determination of sustainable and qualified process in fish oil microencapsulation by spray drying. PMID- 22676456 TI - Eating disorders: challenges in the later phases of the recovery process: a qualitative study of patients' experiences. AB - Scand J Caring Sci; 2013; 27; 92-98 Eating disorders: challenges in the later phases of the recovery process Little is known about how patients experience the later recovery phases of eating disorders. The aim of this study was to describe such experiences using an explorative and descriptive design based on content analysis. Thirteen female patients participated in qualitative interviews. The analysis resulted in four main categories, that is, (i) realising negative consequences, (ii) searching for alternative coping, (iii) searching for normality and identity and (iv) accepting the losses. The categories represent normal psychological processes related to grief, commitment and reconciliation. Such processes may be functionally or dysfunctionally resolved. The clinical implication is that patients in the later recovery phases may need professional help or counselling to accomplish a functional resolving. While in the initial phases of illness and recovery, a focus is on controlling symptoms and the changing of overvalued ideas about weight and shape, therapy in the later recovery phases should focus on the psychological management of the challenges represented in the four categories resulting from the present study. PMID- 22676457 TI - Plasma aldosterone concentration and plasma renin activity decrease during the third trimester in women with twin pregnancies. AB - OBJECTIVE: Changes in the plasma aldosterone concentration (PAC) and the plasma renin activity (PRA) have not been extensively studied in women with twin pregnancies. METHODS: The PAC and PRA levels were determined during the second and third trimesters and on postpartum day 3 in 14 normotensive women with twin pregnancies and 80 normotensive and 7 preeclamptic women with singleton pregnancies. RESULTS: In women with twin pregnancies, elevated PAC and PRA levels (598 +/- 248 pg/mL and 10.0 +/- 4.7 ng/mL/h, respectively) in the second trimester decreased significantly during the third trimester (to 396 +/- 210 pg/mL and 3.5 +/- 2.9 ng/mL/h, respectively), whereas the corresponding PAC increased significantly (from 421 +/- 207 to 667 +/- 371 pg/mL) and the PRA did not change significantly (from 7.3 +/- 3.4 to 6.9 +/- 4.2 ng/mL/h) in women with normal singleton pregnancies. These changes in the PAC and PRA levels in women with twin pregnancies resembled those in hypertensive women with singleton pregnancies. CONCLUSIONS: In women with twin pregnancies, both the PAC and PRA levels were significantly enhanced during the second trimester, whereas those in the third trimester were significantly reduced compared with those in women with normal singleton pregnancies. PMID- 22676458 TI - Interrater and intrarater reliability of photoplethysmography for measuring toe blood pressure and toe-brachial index in people with diabetes mellitus. AB - BACKGROUND: A reliable tool to measure arterial flow to the feet in people with diabetes is required given that they are particularly prone to peripheral arterial disease. Traditionally, the ankle brachial index (ABI) has been used to measure arterial circulation, but its application is limited due to calcification of larger arteries. More recently, toe pressure and the toe brachial index (TBI) has been suggested as superior to ABI measurements because they assess smaller digital arteries less prone to arterial calcification. However, reliability studies for the clinical use of photoplethysmography (PPG) in people with diabetes are lacking. METHODS: Sixty people with diabetes mellitus (35 males and 25 females, mean age 59.6 yrs) consented to take part in the study. The majority (92%) had type 2 diabetes and 8% had type 1 diabetes. Forty-three percent were diagnosed as having peripheral neuropathy when tested using a biothesiometer and 15% were current smokers (10 - 40/day). A podiatrist and a diabetes educator measured toe and brachial blood pressure independently and in a random order using PPG. These measurements were repeated again seven days later, and subsequently analysed with intraclass correlation coefficients (ICC), 95% confidence intervals (CI) and standard error of measurement (SEM). RESULTS: The intrarater reliability of measuring toe pressures was excellent (ICC3,1 =0.78 0.79, SEM 8 mmHg) and interrater reliability was also excellent (ICC2,2 = 0.93, SEM 4 mmHg). The intrarater reliability for measuring brachial pressures was generally poor (ICC3,1 = 0.40 - 0.42, SEM 19 mmHg) and interrater reliability was fair-good (ICC2,2. 0.65, SEM 14 mmHg). The TBI intrarater reliability was fair good (ICC3,1 = 0.51-0.72, SEM 0.08), whilst the interrater reliability of TBI was excellent (ICC2,2 = 0.85, SEM 0.07). CONCLUSIONS: Based on these results, interrater and intrarater reliability of PPG is excellent for measuring toe blood pressure, good for TBI and only fair for brachial pressures in people with diabetes mellitus. PMID- 22676460 TI - Resilience, syndemic factors, and serosorting behaviors among HIV-positive and HIV-negative substance-using MSM. AB - Serosorting is commonly employed by MSM to reduce HIV risk. We hypothesize that MSM perceive serosorting to be effective, and that serosorting is predicted by resilience and inversely related to syndemic characteristics. Surveys included 504 substance-using MSM. Logistic regression models examined syndemic and resilience predictors of serosorting, separately by serostatus. For HIV-positive men, positive coping behaviors (P = .015) and coping self-efficacy (P = .014) predicted higher odds, and cognitive escape behaviors (P = .003) lower odds, of serosorting. For HIV-negative men, social engagement (P = .03) and coping self efficacy (P = .01) predicted higher odds, and severe mental distress (P = .001), victimization history (P = .007) and cognitive escape behaviors (P = .006) lower odds, of serosorting. HIV-negative serosorters reported lower perceptions of risk for infection than non-serosorters (P < .000). Although high risk HIV-negative men may perceive serosorting to be effective, their high rates of UAI and partner change render this an ineffective risk reduction approach. Relevant public health messages are urgently needed. PMID- 22676459 TI - Relation between augmentation index and adiponectin during one-year metformin treatment for nonalcoholic steatohepatosis: effects beyond glucose lowering? AB - BACKGROUND: Insulin resistance (IR) is the major driving force behind development and progression of atherosclerosis in patients with nonalcoholic fatty liver disease (NAFLD). Therefore, correction of IR is a relevant therapeutic target.We performed the current trial to evaluate whether 12- month metformin therapy improves vascular stiffness in patients with NAFLD and to assess if this improvement is associated with change in glucose control, insulin resistance or circulating adiponectin. METHODS: In randomized, placebo controlled study, 63 patients with NAFLD were assigned to one of two groups: Group 1 received daily metformin; Group 2 received placebo. Central aortic augmentation index (AI) was performed using SphygmoCor (version 7.1, AtCor Medical, Sydney, Australia) at baseline, at 4-and 12-month treatment period. Metabolic parameters, insulin resistance markers and serum adiponectin levels were determined. RESULTS: In placebo group: AI did not improve during the treatment period. Liver function and adiponectin levels did not change during the study.In multiple linear regression analysis, the independent predictors of arterial stiffness improvement were metformin treatment and increase in circulating adiponectin levels.Among metformin treated patients: AI decreased significantly during the study. ALP and ALT decreased during initial 4-month treatment period, however raised to the pretreatment levels after 12 months. Serum adiponectin level tended to increase during treatment period with metformin. CONCLUSIONS: Metformin treatment was associated with significant decrease in AI during one year treatment in NAFLD patients. These beneficial vascular effects was associated with exposure to metformin per se as well as change in adiponectin levels suggesting that metformin may mediate its vascular effects via glycemic control-independent mechanisms. PMID- 22676461 TI - The process of adaptation of a community-level, evidence-based intervention for HIV-positive African American men who have sex with men in two cities. AB - We describe the process of adapting a community-level, evidence-based behavioral intervention (EBI), Community PROMISE, for HIV-positive African American men who have sex with men (AAMSM). The Centers for Disease Control and Prevention (CDC) Map of the Adaptation Process (MAP) guided the adaptation process for this new target population by two community-based organizations (CBOs) working in partnership with two research organizations. We describe five steps of the MAP, assessment, selection, preparation, pilot, and implementation, and the use of qualitative interviews, field observations, and a cross-sectional survey. We recommend: (1) development of a centralized interactive website, listserv, or other resources where agencies adapting EBIs can share tools, materials, experiences, lessons learned, and best practices; (2) strengthening Funding Opportunity Announcements by funding incrementally in phases linked to the MAP; and (3) research should examine (a) whether EBIs adapted by CBOs remain efficacious and (b) the best "fit" between the cultural and climate characteristics of effective collaborations between community- and research-based organizations. PMID- 22676462 TI - HIV risk among men who have sex with men who have experienced childhood sexual abuse: systematic review and meta-analysis. AB - Previous research has indicated a high prevalence of childhood sexual abuse (CSA) among men who have sex with men (MSM) in the United States, and has suggested that CSA history is a risk factor for HIV infection in MSM. We conducted a systematic review to identify, synthesize, meta-analyze, and critique the current state of relevant literature. Systematic review methodology was utilized to identify 12 studies that compared MSM with a history of CSA to MSM without a history of CSA on HIV risk indicators including HIV serostatus, sexually transmitted infections (STIs), sexual behaviors, and illicit drug use. Overall, 27.3% (n = 4,263) of the MSM in all included studies (n = 15,622) reported a CSA history. Across the studies that used probabilistic sampling (n = 8,240), the estimated prevalence of CSA was 21.8% (n = 1,800). Meta-analysis indicated that MSM with CSA history were more likely to be HIV positive [odds ratio (OR) = 1.54; 95% confidence interval (CI) = 1.22-1.95)] and to engage in recent unprotected anal intercourse (OR = 1.85, 95% CI = 1.36-2.51). Studies also indicated that MSM with a history of CSA were more likely to report frequent casual male partners, substance use, and sex while under the influence of alcohol or other drugs. Trends across studies indicated a need for interventions to assess CSA history and address effects of CSA on sexual risk behavior of MSM. Inconsistencies across studies indicated a need to reach consensus among researchers and providers in defining CSA. PMID- 22676463 TI - The significance of privacy and trust in providing health-related services to behaviorally bisexual men in the United States. AB - Previous research suggests that bisexual men face unique health concerns in comparison to their exclusively homosexual and heterosexual counterparts. However, little is known about behaviorally bisexual men's experiences with health services, including ways of providing services that would be most appropriate to meet the health needs of this population. This study sought to understand preferences for health-related services among behaviorally bisexual men in the Midwestern United States. Using a community-based research approach, a diverse sample of 75 behaviorally bisexual men was recruited for in-depth interviews. Qualitative data were analyzed utilizing inductive coding through established team-based protocols to ensure reliability. Themes emerged involving the importance of privacy and trust when reaching, recruiting, and engaging behaviorally bisexual men in health services. Findings suggest that multifaceted approaches are needed, including those that provide relevant and confidential services while allowing for the development and ongoing maintenance of trust. PMID- 22676464 TI - Individual-level predictors of nonparticipation and dropout in a life-skills HIV prevention program for adolescents in foster care. AB - The purpose of this study is to identify individual-level characteristics of foster care adolescents who are more likely to not participate in, and drop out of, a life-skills HIV prevention program delivered over 8 months. Structured interviews were conducted with 320 foster care adolescents (15-18 years). Logistic regression and survival analyses (Cox Proportional Hazards Regression) determined the influence of demographics, HIV sexual risk behaviors, substance use, mental health problems, and other individual-level risk factors on nonparticipation and dropout. Older age and having vaginal intercourse without a condom were significant predictors of nonparticipation. Older age and marijuana use significantly increased the hazard of dropping out of the program. Foster care adolescents at increased risk for HIV infection were more likely to never participate in and drop out of the program. To improve initial and ongoing participation, HIV prevention efforts for adolescents in foster care should be tailored to individual-level HIV risk behaviors and incorporate early and ongoing engagement and retention strategies. PMID- 22676465 TI - HIV risk behavior and access to services: what predicts HIV testing among heterosexually active homeless men? AB - HIV is a serious epidemic among homeless persons, where rates of infection are estimated to be three times higher than in the general population. HIV testing is an effective tool for reducing HIV transmission and for combating poor HIV/AIDS health outcomes that disproportionately affect homeless persons, however, little is known about the HIV testing behavior of homeless men. This study examined the association between individual (HIV risk) and structural (service access) factors and past year HIV testing. Participants were a representative sample of 305 heterosexually active homeless men interviewed from meal programs in the Skid Row region of Los Angeles. Logistic regression examined the association between past year HIV testing and demographic characteristics, HIV risk behavior, and access to other services in the Skid Row area in the past 30 days. Despite high rates of past year HIV testing, study participants also reported high rates of HIV risk behavior, suggesting there is still significant unmet need for HIV prevention among homeless men. Having recently used medical/dental services in the Skid Row area (OR: 1.91; CI: 1.09, 3.35), and being a military veteran (OR: 2.10; CI: 1.01 4.37) were significantly associated with HIV testing service utilization. HIV testing was not associated with HIV risk behavior, but rather with access to services and veteran status, the latter of which prior research has linked to increased service access. We suggest that programs encouraging general medical service access may be important for disseminating HIV testing services to this high-risk, vulnerable population. PMID- 22676466 TI - Impact of an Asha intervention on depressive symptoms among rural women living with AIDS in India: comparison of the Asha-Life and Usual Care program. AB - The purpose of this randomized pilot study is to conduct an intervention with 68 rural women living with AIDS to compare the effectiveness of two different programs on depressive symptoms. The trial was designed to assess the impact of the Asha-Life intervention engaging with an HIV-trained village woman, Asha (Accredited Social Health Activist), to participate in the care of women living with AIDS (WLA), along with other health care providers compared to a Usual Care group. Two high prevalence HIV/AIDS villages in rural Andhra Pradesh, which were demographically alike and served by distinct Public Health Centers, were selected randomly from a total of 16 villages. The findings of this study demonstrated that the Asha-Life participants significantly reduced their depressive symptom scores compared to the Usual Care participants. Moreover, women living with AIDS who demonstrated higher depressive symptom scores at baseline had greater reduction in their depressive symptoms than women with lower scores. PMID- 22676468 TI - Predictors of psychological adjustment, experienced parenting burden and chronic sorrow symptoms in parents of children with cerebral palsy. AB - AIM: To investigate the role of child behaviour, parental coping and experiential avoidance in predicting the psychological outcomes of: (i) psychological symptoms; (ii) chronic sorrow symptoms; and (iii) experienced parenting burden in parents of children with cerebral palsy (CP). METHOD: This study is a cross sectional, correlational study. Ninety-four parents of children (aged 2-12 years) with CP (various levels of motor functioning GMFCS I-V) participated. RESULTS: Together, the three predictors of child behaviour, parental coping and experiential avoidance explained 36.8% of the variance in psychological symptoms with child behavioural problems and experiential avoidance as significant unique predictors. In addition, 15.8% of the variance in chronic sorrow symptoms was explained by the three predictors with experiential avoidance alone as a significant unique predictor. Lastly, the predictors together explained 24.3% of the variance in experienced parenting burden with child behavioural problems and experiential avoidance as significant unique predictors. CONCLUSIONS: This study demonstrates a relationship between child behavioural problems and parental psychological symptoms and experienced parenting burden as well as a relationship between experiential avoidance and parental psychological symptoms, experienced parenting burden and chronic sorrow symptoms. PMID- 22676467 TI - Histone deacetylase-4 is required during early cranial neural crest development for generation of the zebrafish palatal skeleton. AB - BACKGROUND: Histone deacetylase-4 (Hdac4) is a class II histone deacetylase that inhibits the activity of transcription factors. In humans, HDAC4 deficiency is associated with non-syndromic oral clefts and brachydactyly mental retardation syndrome (BDMR) with craniofacial abnormalities. RESULTS: We identify hdac4 in zebrafish and characterize its function in craniofacial morphogenesis. The gene is present as a single copy, and the deduced Hdac4 protein sequence shares all known functional domains with human HDAC4. The zebrafish hdac4 transcript is widely present in migratory cranial neural crest (CNC) cells of the embryo, including populations migrating around the eye, which previously have been shown to contribute to the formation of the palatal skeleton of the early larva. Embryos injected with hdac4 morpholinos (MO) have reduced or absent CNC populations that normally migrate medial to the eye. CNC-derived palatal precursor cells do not recover at the post-migratory stage, and subsequently we found that defects in the developing cartilaginous palatal skeleton correlate with reduction or absence of early CNC cells. Palatal skeletal defects prominently include a shortened, clefted, or missing ethmoid plate, and are associated with a shortening of the face of young larvae. CONCLUSIONS: Our results demonstrate that Hdac4 is a regulator of CNC-derived palatal skeletal precursors during early embryogenesis. Cleft palate resulting from HDAC4 mutations in human patients may result from defects in a homologous CNC progenitor cell population. PMID- 22676469 TI - Evaluation of elevated alanine aminotransferase and hepatitis B virus DNA in healthy seronegative blood donors. AB - BACKGROUND: Serum alanine transaminase (ALT) has been used as a surrogate marker for detection of hepatitis B and C in blood donors in Pakistan since 1985. Since the introduction of more sensitive assays the value of ALT became questionable but it was still used with subsequent wastage of blood units with raised ALT. FINDINGS: We conducted a study for a period of one year to evaluate the usefulness of ALT. During the study period, 25117 subjects donated blood. Eight hundred and seventy two donors (3.4%) were positive for one or more serological tests. ALT of all donors ranged from 0-1501 U/L (Mean +/- SD; 33.4 +/- 25.45U/L). The donors seronegative for all disease markers were 24245 (96.6%). Of these, 21164 (84.2%) donors had their ALT within reference range while 2874 (11.4%) and 207 (0.8%) of donors had minimal and markedly elevated results respectively. Six hundred and twenty one blood units (including red cells, platelets and plasma) were discarded based on elevated ALT results alone at a cost of $39,123. Two hundred seronegative blood donors with normal ALT, minimally and markedly elevated ALT levels, were selected randomly and evaluated for hepatitis B deoxynucleic acid by individual PCR. None of the donors was found to be reactive. CONCLUSION: This work did not support a positive association between hepatitis B virus nucleic acid and elevated ALT in healthy serologically negative blood donors. PMID- 22676471 TI - Does Langenskiold staging have a good prognostic value in late onset tibia vara? AB - BACKGROUND: Although many literature studied the effect of many factors on the prognosis of the early-onset Blount disease, studies that were written on the prognostic factors affecting late onset tibia vara are still limited. PURPOSE: The aim of this study is to evaluate the prognostic value of the Langenskiold classification system for late onset tibia vara. METHODS: Twenty children from the Sporting Health Insurance Student Reference Hospital-Alexandria, with a diagnosis of late onset tibia vara were evaluated for the effect of the Langenskiold staging system on the prognosis after they all had been treated by gradual correction by Ilizarov technique using the so called "juxta-articular hinge assembly" after a mean follow-up period of 4.9 years (range : 4-6, SD 0.75). RESULTS: The difference in varus recurrence rates between the "low grade group" and "high grade group" was found to be statistically significant (p = 0.008) as will be discussed later. There was no statistically significant relation between the age of the patients at the time of operation, sex, length of the follow up period and the degree of pre-operative varus deformity angle (DA) and the recurrence (p > 0.05). CONCLUSION: We concluded that Langenskiold staging system is a reliable, reproducible and a good prognostic factor for late onset tibia vara. PMID- 22676472 TI - Ligand exchange inducing efficient incorporation of CisPt derivatives into Ureasil-PPO hybrid and their interactions with the multifunctional hybrid network. AB - Efficient incorporation of (PtCl3EtOH)(-) anion derived from CisPt moiety into ureasil-PPO (poly(propylene oxide)) network was achieved from one-pot sol-gel synthesis carried out in the presence of water, HCl, and ethanol. Reactant proportion was adequately chosen to lead the sol-gel formation of siloxane nodes at the end of short PPO chains, to prevent the CisPt hydrolysis, and to induce platinum ligand exchange. The efficient dissolution of Pt species and the formation of a homogeneous liquid-like solution on the transparent and elastomeric ureasil-PPO hybrid were evidenced by differential scanning calorimetry and small-angle X-ray scattering. The CisPt ligand exchange and the formation of a Zeise-type salt Y(+)(PtCl3R)(-) were demonstrated by Raman spectroscopy and Pt L3-edge EXAFS analysis. In light of these results and in agreement with the proportion of reactants introduced in the media for synthesis and those self-produced by hydrolysis and condensation processes, we proposed for R the ethanol moiety and for Y the ammonium cation. The Raman spectroscopy studies indicated also that the ammonium cations are coordinated by the ether type oxygen atoms of the PPO chains backbone, whereas the amine groups of the urea linkage participate in the (PtCl3EtOH)(-) anion coordination. In situ Raman monitoring of Pt species decomplexation induced by immersion of hybrid matrix in water highlighted the specific participation of Pt ligands in interaction with the urea group and of NH4(+) cations coordinated by ether-type oxygen atoms in the formation of supramolecular interactions between the PPO chains. The electrospray mass spectrometry analysis of the Pt species released in water from the ureasil-PPO hybrid evidenced that the structure of the complex, NH4 (PtCl3 EtOH), incorporated in the matrix is totally preserved after delivery. Due to both well-known antitumoral and catalytic activities of Pt species, the results reported herein are of prime importance for further applications as drug delivery systems with optimized release pattern or as potential materials for new conceptual development of in situ catalyst delivery in homogeneous catalysis. PMID- 22676470 TI - Polyclonal HER2-specific antibodies induced by vaccination mediate receptor internalization and degradation in tumor cells. AB - INTRODUCTION: Sustained HER2 signaling at the cell surface is an oncogenic mechanism in a significant proportion of breast cancers. While clinically effective therapies targeting HER2 such as mAbs and tyrosine kinase inhibitors exist, tumors overexpressing HER2 eventually progress despite treatment. Thus, abrogation of persistent HER2 expression at the plasma membrane to synergize with current approaches may represent a novel therapeutic strategy. METHODS: We generated polyclonal anti-HER2 antibodies (HER2-VIA) by vaccinating mice with an adenovirus expressing human HER2, and assessed their signaling effects in vitro and anti-tumor effects in a xenograft model. In addition, we studied the signaling effects of human HER2-specific antibodies induced by vaccinating breast cancer patients with a HER2 protein vaccine. RESULTS: HER2-VIA bound HER2 at the plasma membrane, initially activating the downstream kinases extracellular signal regulated protein kinase 1/2 and Akt, but subsequently inducing receptor internalization in clathrin-coated pits in a HER2 kinase-independent manner, followed by ubiquitination and degradation of HER2 into a 130 kDa fragment phosphorylated at tyrosine residues 1,221/1,222 and 1,248. Following vaccination of breast cancer patients with the HER2 protein vaccine, HER2-specific antibodies were detectable and these antibodies bound to cell surface-expressed HER2 and inhibited HER2 signaling through blocking tyrosine 877 phosphorylation of HER2. In contrast to the murine antibodies, human anti-HER2 antibodies induced by protein vaccination did not mediate receptor internalization and degradation. CONCLUSION: These data provide new insight into HER2 trafficking at the plasma membrane and the changes induced by polyclonal HER2-specific antibodies. The reduction of HER2 membrane expression and HER2 signaling by polyclonal antibodies induced by adenoviral HER2 vaccines supports human clinical trials with this strategy for those breast cancer patients with HER2 therapy-resistant disease. PMID- 22676473 TI - Comparison of the gene transfer efficiency of mRNA/GL67 and pDNA/GL67 complexes in respiratory cells. AB - Complexes between mRNA and GL67:DOPE:DMPE-PEG5000 (GL67) liposomes were formulated and characterized. Subsequently, the in vitro and in vivo expression characteristics of mRNA/GL67 complexes and pDNA/GL67 complexes, each produced at their optimal ratio, were compared in respiratory cells. Transfection of A549 cells with mRNA/GL67 complexes resulted in a much faster expression than after transfection with pDNA/GL67 complexes. The percentage of GFP-positive cells after mRNA and pDNA transfection peaked after 8 and 24 h, respectively. At these time points the percentage of GFP-positive cells was two times higher after mRNA transfection than after pDNA transfection. Furthermore, the efficacy of mRNA/GL67 complexes was independent of the cell cycle. This was in sharp contrast with pDNA/GL67 complexes that caused only a weak expression in nondividing cells. This confirms that the nuclear barrier is a crucial obstacle for pDNA but not for mRNA. Finally, mRNA/GL67 and pDNA/GL67 complexes encoding luciferase were administered intranasally to the lungs of mice. The mRNA/GL67 complexes did not give rise to a measurable luciferase expression in the murine lungs. In contrast, a detectable bioluminescent signal was present in the lungs of mice that received the pDNA/GL67 complexes. We showed that mRNA/GL67 complexes have a lower stability in biological fluids. Consequently, this may be an explanation for their lower performance in vivo. PMID- 22676474 TI - The "Texas-sized" molecular box: a versatile building block for the construction of anion-directed mechanically interlocked structures. AB - Over the last two decades, researchers have focused on the synthesis and development of mechanically interlocked molecules (MIMs). The intramolecular motion of mechanical bonds and the ability to induce this effect with the choice of the proper external stimuli has prompted the development of macromolecular systems that possess the ability to "perform work" at the molecular level. Currently, researchers are working to incorporate interlocked species into complex structural systems, such as molecular frameworks and nanoparticles, and to create ever more elegant noncovalent architectures. This effort provides an incentive to generate new building blocks for the construction of MIMs. In this Account, we describe progress in the development of a new cationic building block inspired by the "blue box" of Stoddart and collaborators. The blue box (cylcobis(paraquat-p-phenylene) or CBPQT(4+)) is a tetracationic, electron deficient macrocycle widely recognized for its role in the construction of MIMs. This venerable receptor displays a high affinity for a variety of pi-donor guests, and researchers have used them to construct a wide range of molecular and supramolecular structures, including rotaxanes, catenanes, pseudorotaxanes, polypseudorotaxanes, pseudo[n]polyrotaxanes, and electrochemically switchable molecules. To date, several synthetic analogues of the basic CBPQT(4+) structure have been reported, including systems containing biphenylene linkers and chiral tetracationic cyclophanes. However, researchers have not yet fully generalized the promise of the blue box. In this Account, we chronicle the development of a larger, more flexible tetracationic macrocycle, referred to as the "Texas-sized" molecular box. To highlight its relatively increased size and to distinguish it from CBPQT(4+), we have chosen to color this new receptor burnt orange. The Texas sized box (cyclo[2](2,6-di(1H-imidazol-1-yl)pyridine)[2](1,4-dimethylenebenzene), 1(4+).4PF(6)(-)) acts as a dynamic molecular receptor that displays an ability to adjust its shape and conformation to accommodate anionic guests of different size and charge within its central core. The use of different guests can favor different binding modes and promote the formation of different macromolecular aggregates. Furthermore, the proper selection of the guest allows for the "turning on" or "turning off" of molecular threading and can be used to produce new kinds of threaded species. This dynamic behavior is a special feature of the Texas-sized molecular box, as is its ability to stabilize a range of polypseudorotaxanes, rotaxane-containing metal-organic frameworks (MORFs), and rotaxane-based supramolecular organic frameworks (RSOFs). PMID- 22676475 TI - Diet in subjects with irritable bowel syndrome: a cross-sectional study in the general population. AB - BACKGROUND: Patients with irritable bowel syndrome (IBS) often relate symptoms to the intake of certain foods. This study assesses differences in diet in subjects with and without IBS. METHODS: The cross-sectional, population-based study was conducted in Norway in 2001. Out of 11078 invited subjects, 4621 completed a survey about abdominal complaints and intake of common food items. IBS and IBS subgroups were classified according to Rome II criteria. RESULTS: IBS was diagnosed in 388 subjects (8.4%) and, of these, 26.5% had constipation predominant IBS (C-IBS), 44.8% alternating IBS (A-IBS), and 28.6% diarrhoea predominant IBS (D-IBS). Low intake of dairy products (portions/day) (Odds Ratio 0.85 [CI 0.78 to 0.93], p = 0.001) and high intake of water (100 ml/day) (1.08 [1.02 to 1.15], p = 0.002), tea (1.05 [1.01 to 1.10], p = 0.019) and carbonated beverages (1.07 [1.01 to 1.14], p = 0.023) were associated with IBS. A lower intake of dairy products and a higher intake of alcohol and carbonated beverages were associated with D-IBS and a higher intake of water and tea was associated with A-IBS. In subjects with IBS the severity of symptoms was associated with a higher intake of vegetables and potatoes in subjects with C-IBS, with a higher intake of vegetables in subjects with A-IBS, and with a higher intake of fruits and berries, carbonated beverages and alcohol in subjects with D-IBS. CONCLUSIONS: In this study, the diet differed in subjects with and without IBS and between IBS subgroups and was associated with the severity of symptoms. PMID- 22676476 TI - Development of method for evaluating cell hardness and correlation between bacterial spore hardness and durability. AB - BACKGROUND: Despite the availability of conventional devices for making single cell manipulations, determining the hardness of a single cell remains difficult. Here, we consider the cell to be a linear elastic body and apply Young's modulus (modulus of elasticity), which is defined as the ratio of the repulsive force (stress) in response to the applied strain. In this new method, a scanning probe microscope (SPM) is operated with a cantilever in the "contact-and-push" mode, and the cantilever is applied to the cell surface over a set distance (applied strain). RESULTS: We determined the hardness of the following bacterial cells: Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and five Bacillus spp. In log phase, these strains had a similar Young's modulus, but Bacillus spp. spores were significantly harder than the corresponding vegetative cells. There was a positive, linear correlation between the hardness of bacterial spores and heat or ultraviolet (UV) resistance. CONCLUSIONS: Using this technique, the hardness of a single vegetative bacterial cell or spore could be determined based on Young's modulus. As an application of this technique, we demonstrated that the hardness of individual bacterial spores was directly proportional to heat and UV resistance, which are the conventional measures of physical durability. This technique allows the rapid and direct determination of spore durability and provides a valuable and innovative method for the evaluation of physical properties in the field of microbiology. PMID- 22676477 TI - Predictive value of IgE/IgG4 antibody ratio in children with egg allergy. AB - BACKGROUND: The aim of this study was to investigate the role of specific IgG4 antibodies to hen's egg white and determine their utility as a marker for the outcome of oral challenge test in children sensitized to hen's egg METHODS: The hen's egg oral food challenge test was performed in 105 sensitized children without atopic dermatitis, and the titers of egg white-specific immunoglobulin G4 (IgG4) and immunoglobulin E (IgE) antibodies were measured. To set the cut-off values of IgG4, IgE, and the IgE/IgG4 ratio for predicting positive results in oral challenges, receiver operating characteristic curves were plotted and the area under the curves (AUC) were calculated. RESULTS: Sixty-four of 105 oral challenges with whole eggs were assessed as positive. The AUC for IgE, IgG4, and IgE/IgG4 for the prediction of positive results were 0.609, 0.724, and 0.847, respectively. Thus, the IgE/IgG4 ratio generated significantly higher specificity, sensitivity, positive predictive value (%), and negative predictive value (%) than the individual IgE and IgG4. The negative predictive value of the IgE/IgG4 ratio was 90% at a value of 1. CONCLUSIONS: We have demonstrated that the egg white-specific serum IgE/IgG4 ratio is important for predicting reactivity to egg during food challenges. PMID- 22676478 TI - Mode of anaesthetic for category 1 caesarean sections and neonatal outcomes. AB - BACKGROUND: Birth by emergency caesarean section (CS) is common and often considered urgent (category 1). In the UK, over half of all category 1 CS are performed under general anaesthesia (GA). In this setting, little is known about the effect of the mode of anaesthesia on the neonate. METHODS: A retrospective cohort study was performed using routinely collected de-identified data from Mater Health Services, Brisbane, Australia. The data set included 533 term babies born by category 1 CS for presumed fetal compromise between 2008 and 2011. Bivariate and multivariate analyses were undertaken. RESULTS: The outcomes of 81 babies born by GA CS were compared with 452 by CS under regional anaesthesia (RA). Compared with a category 1 CS under RA, the decision-to-delivery interval for a GA CS was almost eight minutes faster (24.7 vs 32.6 minutes; P < 0.001). When adjusted for confounders, babies born by category 1 GA CS were significantly more likely to have an Apgar score < 7 at five minutes (aOR 6.89; 95%CI 1.79 26.55; P = 0.005), to require Neopuff or bag/mask ventilation for > 60 seconds (aOR 2.34; 95%CI 1.13-4.84; P = 0.022) and to be admitted to a neonatal intensive care nursery (aOR 2.24; 95%CI 1.16-4.31; P = 0.016). CONCLUSIONS: General anaesthesia was associated with short-term neonatal morbidity of term babies born by category 1 CS for presumed fetal compromise, despite enabling a more rapid delivery of the baby. These data should help inform the discussion between anaesthetist and obstetrician, in balancing the risks and benefits of the mode of anaesthesia. PMID- 22676479 TI - In situ measurement of magnesium carbonate formation from CO2 using static high pressure and -temperature 13C NMR. AB - We explore a new in situ NMR spectroscopy method that possesses the ability to monitor the chemical evolution of supercritical CO(2) in relevant conditions for geological CO(2) sequestration. As a model, we use the fast reaction of the mineral brucite, Mg(OH)(2), with supercritical CO(2) (88 bar) in aqueous conditions at 80 degrees C. The in situ conversion of CO(2) into metastable and stable carbonates is observed throughout the reaction. After more than 58 h of reaction, the sample was depressurized and analyzed using in situ Raman spectroscopy, where the laser was focused on the undisturbed products through the glass reaction tube. Postreaction, ex situ analysis was performed on the extracted and dried products using Raman spectroscopy, powder X-ray diffraction, and magic-angle spinning (1)H-decoupled (13)C NMR. These separate methods of analysis confirmed a spatial dependence of products, possibly caused by a gradient of reactant availability, pH, and/or a reaction mechanism that involves first forming hydroxy-hydrated (basic, hydrated) carbonates that convert to the end-product, anhydrous magnesite. This carbonation reaction illustrates the importance of static (unmixed) reaction systems at sequestration-like conditions. PMID- 22676480 TI - Sensitive determination of (-)-epigallocatechin gallate in tea infusion using a novel ionic liquid carbon paste electrode. AB - This paper investigates the electrocatalytic oxidation of (-)-epigallocatechin gallate (EGCG), the main monomer flavanol found in green tea, with a novel ionic liquid, n-octylpyridinium hexafluorophosphate (OPFP) carbon paste electrode (CPE). Due to the natural viscosity and high conductivity of OPFP, this novel OPFP-CPE exhibited very attractive properties, such as high stability and electrochemical reactivity, low background current, and wide electrochemical window. Therefore, this electrode is a very good alternative to traditional chemically modified electrodes because the electrocatalytic effect can achieved without any further electrode modification. Comparative experiments were carried out using CPE and a glassy carbon electrode (GCE). With OPFP-CPE, highly reproducible and well-defined cyclic voltammograms were obtained for EGCG. Under optimal experimental conditions, the peak current of differential pulse voltammetry (DPV) response increased linearly with EGCG concentration over the range of 5.0 * 10(-7)-1.25 * 10(-5) M. The limit of detection (LOD) and the limit of quantification (LOQ) were 1.32 * 10(-7) and 4.35 * 10(-7) M, respectively. The method was applied to the determination of EGCG in green tea infusion samples, and the recovery of the spiked EGCG to the diluted (10-fold) tea extract was from 87.62 to 99.51%. PMID- 22676481 TI - Variance in direct exposure measures of typing force and wrist kinematics across hours and days among office computer workers. AB - To determine the number of direct measurements needed to obtain a representative estimate of typing force and wrist kinematics, continuous measures of keyboard reaction force and wrist joint angle were collected at the workstation of 22 office workers while they completed their own work over three days, six hours per day. Typing force and wrist kinematics during keyboard, mouse and idle activities were calculated for each hour of measurement along with variance in measurements between subjects and between day and hour within subjects. Variance in measurements between subjects was significantly greater than variance in measurements between days and hours within subjects. Therefore, we concluded a single, one-hour period of continuous measures is sufficient to identify differences in typing force and wrist kinematics between subjects. Within subjects, day and hour of measurement had a significant effect on some measures and thus should be accounted for when comparing measures within a subject. PRACTITIONER SUMMARY: The dose response relationship between exposure to computer related biomechanical risk factors and musculoskeletal disorders is poorly understood due to the difficulty and cost of direct measures. This study demonstrates a single hour of direct continuous measures is sufficient to identify differences in wrist kinematics and typing force between individuals. PMID- 22676483 TI - Ordered mesoporous silica material SBA-15: loading of new calcium channel blocker -lacidipine. AB - Mesoporous material SBA-15 of hexagonal structure was synthesised and its usefulness as a carrier for a poorly soluble drug--lacidipine (LA)--was tested. The source of silica was tetraethyl orthosilicate (TEOS) and the structure ordering agent was non-ionic surfactant Pluronic P123. SBA-15 with encapsulated LA was characterised by X-ray diffraction (XRD), infrared spectroscopy (FTIR), thermogravimetry (TG), differential scanning calorimetry (DSC) and transmission electron microscopy (TEM). Adsorption of the therapeutically active substance was performed in anhydrous environment (chloroform). The content of the therapeutic substance in SBA-15 estimated from TG measurements reached 9%. The properties of the compound obtained were compared with those of a physical mixture of the components. PMID- 22676484 TI - Females without reflux symptoms or gastroesophageal reflux disease have less distal esophageal acid exposure than males without reflux symptoms or gastroesophageal reflux disease. AB - Ambulatory 24-hour esophageal pH monitoring is the gold standard examination to assess esophageal acid exposure. Gender-related variation is a well-recognized physiologic phenomenon in health and disease. To date, limited gender-specific 24 hour esophageal pH monitoring data are available. The aim of this study was to obtain values of esophageal pH monitoring in males and females without reflux symptoms or gastroesophageal reflux disease (GERD) to determine if gender variation exists in esophageal acid exposure among individuals without these factors. Twenty-four-hour dual esophageal pH monitoring was performed in male and female volunteers without reflux symptoms or GERD. Values for total number of reflux episodes, episodes longer than 5 minutes, total reflux time in minutes, % time with pH below 4, and longest reflux episode in the proximal/distal esophagus were obtained and recorded for both groups. The distal channel was placed 5 cm and proximal channel 15 cm above the manometrically determined lower esophageal sphincter. Means were compared using an independent sample t-test. Sixty-seven males and 69 females were enrolled. All subjects completed esophageal 24-hour pH monitoring without difficulty. There was no age or body mass difference between groups. Females had significantly fewer reflux episodes at both esophageal measuring sites and, significantly less total reflux time and % time with pH below 4 in the distal esophagus than males. All other parameters were similar. Significant gender-related differences exist in esophageal acid exposure, especially in the distal esophagus in individuals without reflux symptoms or GERD. These differences underscore the need for gender-specific reference values for 24-hour pH monitoring, allowing for an accurate evaluation of esophageal acid exposure in symptomatic patients. PMID- 22676485 TI - The effect of lipid and aqueous solubilities on flux of nicotinic acid esters from water through silicone membrane. AB - OBJECTIVE: The maximum fluxes (J(M)) of nicotinic acid esters (NAE) across silicone membranes from water (J(MPAQ)) have been measured to determine how well they correlate with J(M) of NAE across human skin from water in vitro (J(MHAQ)) and in vivo (J(MHAQ1)) and with J(M) of NAE across hairless mouse skin from water (J(MMAQ)). MATERIALS AND METHODS: The NAE were all commercially available. Solubilities in water (S(AQ)), isopropyl myristate (S(IPM)) and octanol (S(OCT)) were obtained from literature sources. J(MPAQ) were measured at saturation for all the esters except the methyl ester. In that case, flux was measured at a concentration (C) less than saturation (J(PAQ)) and converted to J(MPAQ) = (J(PAQ))(S(AQ)/C(AQ)). RESULTS AND DISCUSSION: J(MPAQ) values predicted from the previously reported coefficients to the parameters in the Roberts-Sloan (RS) equation (PRE J(MPAQ)) were substantially lower than the experimental J(MPAQ) values (EXP J(MPAQ)) values obtained here. The EXP J(MPAQ) were incorporated into the previous J(MPAQ) database and new coefficients were obtained: x = -1.837; y = 0.742; z = 0.00435; r2 = 0.86. Correlation of J(MPAQ) values with J(MHAQ), J(MHAQ1), and J(MMAQ) values show the same trend as the J(MPAQ) values. CONCLUSIONS: The inclusion of the NAE n = 6 data into the previous n = 32 database for the permeation of the prodrugs through a silicone membrane from water (J(MPAQ)) greatly improved the fit of the n = 38 database to the RS equation: r2 = 0.86 vs r2 = 0.77. The correlation between log J(MHAQ) and log J(MPAQ) gave r2 = 0.98. This suggests that J(MPAQ) values are good predictors of J(MHAQ) values. PMID- 22676487 TI - Preeclampsia, placenta, oxidative stress, and PMCA. AB - OBJECTIVE: The aim of this study is to summarize the reported evidence on the possible relationship between preeclampsia, placenta, oxidative stress and plasma membrane Ca-ATPase (PMCA) activity, responsible for fine control of intracellular calcium concentration. METHODS: Literature search was conducted in MEDLINE/PubMed and several unpublished results from our laboratory were included. RESULTS: Lipid peroxidation in placental and red blood cell plasma membranes during preeclampsia and a concomitant diminution of their PMCA activity are described. CONCLUSIONS: Uteroplacental hypoperfusion raises lipid peroxidation by-products in the blood plasma that could alter structure and functionality of the cell membranes of the endothelium and several tissues. PMID- 22676486 TI - Recombinant sterol esterase from Ophiostoma piceae: an improved biocatalyst expressed in Pichia pastoris. AB - BACKGROUND: The ascomycete Ophiostoma piceae produces a sterol esterase (OPE) with high affinity towards p-nitrophenol, glycerol and sterol esters. Its hydrolytic activity on natural mixtures of triglycerides and sterol esters has been proposed for pitch biocontrol in paper industry since these compounds produce important economic losses during paper pulp manufacture. RESULTS: Recently, this enzyme has been heterologously expressed in the methylotrophic yeast Pichia pastoris, and the hydrolytic activity of the recombinant protein (OPE*) studied. After the initial screening of different clones expressing the enzyme, only one was selected for showing the highest production rate. Different culture conditions were tested to improve the expression of the recombinant enzyme. Complex media were better than minimal media for production, but in any case the levels of enzymatic activity were higher (7-fold in the best case) than those obtained from O. piceae. The purified enzyme had a molecular mass of 76 kDa, higher than that reported for the native enzyme under SDS-PAGE (60 kDa). Steady-state kinetic characterization of the recombinant protein showed improved catalytic efficiency for this enzyme as compared to the native one, for all the assayed substrates (p-nitrophenol, glycerol, and cholesterol esters). Different causes for this were studied, as the increased glycosylation degree of the recombinant enzyme, their secondary structures or the oxidation of methionine residues. However, none of these could explain the improvements found in the recombinant protein. N-terminal sequencing of OPE* showed that two populations of this enzyme were expressed, having either 6 or 8 amino acid residues more than the native one. This fact affected the aggregation behaviour of the recombinant protein, as was corroborated by analytical ultracentrifugation, thus improving the catalytic efficiency of this enzyme. CONCLUSION: P. pastoris resulted to be an optimum biofactory for the heterologous production of recombinant sterol esterase from O. piceae, yielding higher activity levels than those obtained with the saprophytic fungus. The enzyme showed improved kinetic parameters because of its modified N-terminus, which allowed changes in its aggregation behaviour, suggesting that its hydrophobicity has been modified. PMID- 22676489 TI - Abstracts of the 4th Danish Emergency Medicine Conference. Roskilde, Denmark. November 25-26, 2011. PMID- 22676488 TI - Differential self-assembly behaviors of cyclic and linear peptides. AB - Here we ask the fundamental questions about the effect of peptide topology on self-assembly. The study revealed that the self-assembling behaviors of cyclic and linear peptides are significantly different in several respects, in addition to sharing several similarities. Their clear differences included the morphological dissimilarities of the self-assembled nanostructures and their thermal stability. The similarities include their analogous critical aggregation concentration values and cytotoxicity profiles, which are in fact closely related. We believe that understanding topology-dependent self-assembly behavior of peptides is important for developing tailor-made self-assembled peptide nanostructures. PMID- 22676490 TI - Lesion border detection in dermoscopy images using ensembles of thresholding methods. AB - BACKGROUND: Dermoscopy is one of the major imaging modalities used in the diagnosis of melanoma and other pigmented skin lesions. Due to the difficulty and subjectivity of human interpretation, automated analysis of dermoscopy images has become an important research area. Border detection is often the first step in this analysis. In many cases, the lesion can be roughly separated from the background skin using a thresholding method applied to the blue channel. However, no single thresholding method appears to be robust enough to successfully handle the wide variety of dermoscopy images encountered in clinical practice. METHODS: In this article, we present an automated method for detecting lesion borders in dermoscopy images using ensembles of thres holding methods. CONCLUSION: Experiments on a difficult set of 90 images demonstrate that the proposed method is robust, fast, and accurate when compared to nine state-of-the-art methods. PMID- 22676491 TI - Can withdrawal of CNIs limit the progression of CAN? PMID- 22676493 TI - 'It is life threatening but I don't mind'. A qualitative study using photo elicitation interviews to explore adolescents' experiences of renal replacement therapies. AB - BACKGROUND: Renal replacement therapy (RRT) transforms the life prospects of young people with established renal failure. However, these treatments can have significant physiological and psychological implications for adolescents as they prepare to transition into adulthood. Health policies increasingly emphasize children and youth's active participation and consultation as users of health services, yet studies infrequently seek their experiences directly. METHODS: Adolescents receiving RRT in a large UK teaching hospital took photographs illustrating the impact of their condition and treatment on their lives. Qualitative photo elicitation interviews were conducted to explore the significance of the images and the young person's experiences. Interviews were analysed using descriptive thematic analysis. RESULTS: Ten young people aged 13 17 years participated. Themes identified were: (1) understanding and acceptance of treatment; (2) living in a non-functioning body; (3) impact upon daily life; (4) sources of support. Young people found treatments challenging and experienced significant impact on relationships and daily routines. Yet, health was prioritized over body image and participants demonstrated great emotional resilience. Young people valued support from family and friends, although were wary of disclosing their condition in case it resulted in being highlighted as different. Young people reported hospital staff as being caring and professional, but their biggest virtue appeared to be their willingness to treat the young people as 'normal'. CONCLUSIONS: Young people engaged readily with the research, and frankly described the impact of RRT on their everyday lives. Service providers must ensure that adolescents' developmental needs are met as traditional tasks of adolescence may lose priority. However, it is also clear that young people's ability to cope with treatments should not be underestimated. PMID- 22676494 TI - Factors influencing compliance to hygiene routines in community care - the viewpoint of medically responsible nurses in Sweden. AB - AIMS AND OBJECTIVES: The aim of the study was to describe factors influencing compliance to hygiene routines in community care in Swedish municipalities from the perspective of medically responsible nurses (MRN). METHOD: A web-based questionnaire was sent to all MRNs in Swedish municipalities, N = 268. Beside demographical background data, the questionnaire contained two core open-ended questions generating free text data. Data were analysed with descriptive statistics and qualitative content analysis. RESULT: Four categories of factors were found: resources, management, staff and external factors. All four categories contained subcategories. CONCLUSION: To some extent, the challenges to uphold adequate compliance to hygiene routines seem different in community care than in hospitals. Resources regarding equipment and supplies seem as an uncertain asset and uneven distributed among municipalities. Home likeness was seen as a major obstacle for upholding adequate hygiene routines. To uphold sufficient hygiene routines in a person's home or in a home-like environment might be one of the major challenges for community health care in the future. The MRN's narratives suggest that Registered Nurses have a key role in upholding sufficient hygiene in community care. This report might contribute in providing them with more knowledge to take on this urgent task. PMID- 22676492 TI - Comparative analysis of two phenotypically-similar but genomically-distinct Burkholderia cenocepacia-specific bacteriophages. AB - BACKGROUND: Genomic analysis of bacteriophages infecting the Burkholderia cepacia complex (BCC) is an important preliminary step in the development of a phage therapy protocol for these opportunistic pathogens. The objective of this study was to characterize KL1 (vB_BceS_KL1) and AH2 (vB_BceS_AH2), two novel Burkholderia cenocepacia-specific siphoviruses isolated from environmental samples. RESULTS: KL1 and AH2 exhibit several unique phenotypic similarities: they infect the same B. cenocepacia strains, they require prolonged incubation at 30 degrees C for the formation of plaques at low titres, and they do not form plaques at similar titres following incubation at 37 degrees C. However, despite these similarities, we have determined using whole-genome pyrosequencing that these phages show minimal relatedness to one another. The KL1 genome is 42,832 base pairs (bp) in length and is most closely related to Pseudomonas phage 73 (PA73). In contrast, the AH2 genome is 58,065 bp in length and is most closely related to Burkholderia phage BcepNazgul. Using both BLASTP and HHpred analysis, we have identified and analyzed the putative virion morphogenesis, lysis, DNA binding, and MazG proteins of these two phages. Notably, MazG homologs identified in cyanophages have been predicted to facilitate infection of stationary phase cells and may contribute to the unique plaque phenotype of KL1 and AH2. CONCLUSIONS: The nearly indistinguishable phenotypes but distinct genomes of KL1 and AH2 provide further evidence of both vast diversity and convergent evolution in the BCC-specific phage population. PMID- 22676495 TI - A randomized controlled trial comparing patellar retention versus patellar resurfacing in primary total knee arthroplasty: 5-10 year follow-up. AB - BACKGROUND: The primary purpose of this randomized controlled trial (RCT) was to compare knee-specific outcomes (stiffness, pain, function) between patellar retention and resurfacing up to 10 years after primary total knee arthroplasty (TKA). Secondarily, we compared re-operation rates. METHODS: 38 subjects with non inflammatory arthritis were randomized at primary TKA surgery to receive patellar resurfacing (n = 21; Resurfaced group) or to retain their native patella (n = 17; Non-resurfaced group). Evaluations were performed preoperatively, one, five and 10 years postoperatively by an evaluator who was blinded to group allocation. Self-reported knee-specific stiffness, pain and function, the primary outcomes, were measured by the Western Ontario McMaster Osteoarthritis Index (WOMAC). Revision rate was determined at each evaluation and through hospital record review. RESULTS: 30 (88%) and 23 (72%) of available subjects completed the five and 10-year review respectively. Knee-specific scores continued to improve for both groups over the 10-years, despite diminishing overall health with no significant group differences seen. All revisions occurred within five years of surgery (three Non-resurfaced subjects; one Resurfaced subject) (p = 0.31). Two revisions in the Non-resurfaced group were due to persistent anterior knee pain. CONCLUSIONS: We found no differences in knee-specific results between groups at 5 10 years postoperatively. The Non-resurfaced group had two revisions due to anterior knee pain similar to rates reported in other studies. Knee-specific results provide useful postoperative information and should be used in future studies comparing patellar management strategies. CLINICALTRIALS.GOV IDENTIFIER: NCT01500252. PMID- 22676496 TI - High-throughput preparation of hexagonally ordered mesoporous silica and gadolinosilicate nanoparticles for use as MRI contrast agents. AB - The development of biomedical nanoparticulate materials for use in diagnostics is a delicate balance between performance, particle size, shape, and stability. To identify materials that satisfy all of the criteria it is useful to employ automated high-throughput (HT) techniques for the study of these materials. The structure and performance of surfactant templated mesoporous silica is very sensitive to a wide number of variables. Variables, such as the concentration of the structure-directing agent, the cosolvent and dopant ions and also the temperature and concentration of quenching all have an influence on the structure, surface chemistry, and therefore, the performance of the mesoporous silica nanoparticles generated. Using an automated robotic synthetic platform, a technique has been developed for the high-throughput preparation of mesoporous silica and gadolinium-doped silicate (gadoliniosilicate) nanoparticulate MRI contrast agents. Twelve identical repeats of both the mesoporous silica and gadolinosilicate were synthesized to investigate the reproducibility of the HT technique. Very good reproducibility in the production of the mesoporous silica and the gadolinosilcate materials was obtained using the developed method. The performance of the gadolinosilicate materials was comparable as a T(1) agent to the commercial MRI contrast agents. This HT methodology is highly reproducible and an effective tool that can be translated to the discovery of any sol-gel derived nanomaterial. PMID- 22676498 TI - Public health as an international problem: 1944. PMID- 22676497 TI - A long diagnostic delay in patients with Hereditary Haemorrhagic Telangiectasia: a questionnaire-based retrospective study. AB - BACKGROUND: The difficulty in establishing a timely correct diagnosis is a relevant matter of concern for several rare diseases. Many rare-disease-affected patients suffer from considerable diagnostic delay, mainly due to their poor knowledge among healthcare professionals, insufficient disease awareness among patients' families, and lack of promptly available diagnostic tools. Hereditary Haemorrhagic Telangiectasia (HHT) is an autosomal-dominantly inherited vascular dysplasia, affecting 1:5,000-10,000 patients. HHT is characterized by high variability of clinical manifestations, which show remarkable overlapping with several common diseases. AIM: To perform a detailed analysis concerning the diagnostic time lag occurring in patients with HHT, defined as the time period spanning from the first clinical manifestation to the attainment of a definite, correct diagnosis. METHODS: A questionnaire was administered to the HHT patients previously recruited from 2000 and 2009. Clinical onset, first referral to a physician for disease manifestations, and first correct diagnosis of definite HHT were collected. Eventual misdiagnosis at first referral and serious complications occurring throughout the time elapsing between disease onset and definite diagnosis were also addressed. RESULTS: In the 233 respondents, the clinical onset of disease occurred at an age of 14.1 yrs, while the age of first referral and the age of first definite diagnosis of HHT were 29.2 yrs and 40.1 yrs, respectively. Only 88/233 patients received a correct diagnosis at first counseling. Thus, the diagnostic time lag, represented by the time elapsing from disease onset and first definite diagnosis of HHT, proved to be 25.7 yrs. Twenty two patients suffered from severe complications during this time interval. The diagnostic delay was significantly longer (p < 0.001) in index patients (first patients who attained definite HHT diagnosis in a given family) than in non-index patients (relative of index patients). The diagnostic time lag was also significantly associated with education grade (p < 0.001). CONCLUSIONS: Our data report for the first time a systematic inquiry of diagnostic delay in HHT showing that patients receive a definite diagnosis only after nearly three decades from disease onset. Concerted efforts are still to be made to increase awareness of this disease among both families and physicians. PMID- 22676499 TI - Maternal exposure to intimate partner violence and the risk of undernutrition among children younger than 5 years in Bangladesh. AB - OBJECTIVES: We examined the association between maternal experiences of intimate partner violence (IPV) and the risk of undernutrition among children younger than 5 years in Bangladesh. METHODS: We used data from the 2007 Bangladesh Demographic Health Survey. Our analyses were based on the responses of 1851 married women living with at least 1 child younger than 5 years. Exposure was determined from maternal reports of physical and sexual IPV. Outcomes included underweight, stunting, and wasting. RESULTS: Twenty-nine percent of the respondents had experienced IPV in the year preceding the survey. Maternal experience of any physical or sexual IPV was associated with an increased risk of stunting (adjusted odds ratio [AOR] =1.59; 95% confidence interval [CI] =1.23, 2.08) and underweight (AOR =1.33; 95% CI=1.04, 1.71) but was not significantly associated with wasting (AOR=1.08; 95% CI=0.78, 1.49). CONCLUSIONS: The association between maternal exposure to physical or sexual IPV and child underweight and stunting suggests that partner violence plays a significant role in compromising child health by impairing child nutrition. Our findings reinforce the evidence that improving child nutrition is an additional reason to strengthen efforts to protect women from physical and sexual IPV. PMID- 22676501 TI - Cost comparison of 2 mass vaccination campaigns against influenza A H1N1 in New York City. AB - Objectives. We estimated and compared total costs and costs per dose administered for 2 influenza A 2009 monovalent vaccine campaigns in New York City: an elementary school-located campaign targeting enrolled children aged 4 years and older, and a community-based points-of-dispensing campaign for anyone aged 4 years and older. Methods. We determined costs from invoices or we estimated costs. We obtained vaccination data from the Citywide Immunization Registry and reports from the community points of dispensing. Results. The school campaign delivered approximately 202,089 vaccines for $17.9 million and $88 per dose. The community campaign delivered 49,986 vaccines for $7.6 million and $151 per dose. At projected capacity, the school campaign could have delivered 371,827 doses at $53 each or $13 each when we excluded the value of in-kind resources. The community points of dispensing could have administered 174,000 doses at $51 each or $24 each when we excluded the value of in-kind resources. Conclusions. The school campaign delivered vaccines at a lower cost per dose than did the community campaign. Had demand been higher, both campaigns may have delivered vaccine at lower, more comparable cost per dose. PMID- 22676500 TI - Correlates of suicidality: investigation of a representative sample of Manitoba First Nations adolescents. AB - OBJECTIVES: We examined individual, friend or family, and community or tribe correlates of suicidality in a representative on-reserve sample of First Nations adolescents. METHODS: Data came from the 2002-2003 Manitoba First Nations Regional Longitudinal Health Survey of Youth. Interviews were conducted with adolescents aged 12 to 17 years (n=1125) from 23 First Nations communities in Manitoba. We used bivariate logistic regression analyses to examine the relationships between a range of factors and lifetime suicidality. We conducted sex-by-correlate interactions for each significant correlate at the bivariate level. A multivariate logistic regression analysis identified those correlates most strongly related to suicidality. RESULTS: We found several variables to be associated with an increased likelihood of suicidality in the multivariate model, including being female, depressed mood, abuse or fear of abuse, a hospital stay, and substance use (adjusted odds ratio range=2.43-11.73). Perceived community caring was protective against suicidality (adjusted odds ratio=0.93; 95% confidence interval=0.88, 0.97) in the same model. CONCLUSIONS: Results of this study may be important in informing First Nations and government policy related to the implementation of suicide prevention strategies in First Nations communities. PMID- 22676502 TI - Use of design effects and sample weights in complex health survey data: a review of published articles using data from 3 commonly used adolescent health surveys. AB - OBJECTIVES: We assessed how frequently researchers reported the use of statistical techniques that take into account the complex sampling structure of survey data and sample weights in published peer-reviewed articles using data from 3 commonly used adolescent health surveys. METHODS: We performed a systematic review of 1003 published empirical research articles from 1995 to 2010 that used data from the National Longitudinal Study of Adolescent Health (n=765), Monitoring the Future (n=146), or Youth Risk Behavior Surveillance System (n=92) indexed in ERIC, PsycINFO, PubMed, and Web of Science. RESULTS: Across the data sources, 60% of articles reported accounting for design effects and 61% reported using sample weights. However, the frequency and clarity of reporting varied across databases, publication year, author affiliation with the data, and journal. CONCLUSIONS: Given the statistical bias that occurs when design effects of complex data are not incorporated or sample weights are omitted, this study calls for improvement in the dissemination of research findings based on complex sample data. Authors, editors, and reviewers need to work together to improve the transparency of published findings using complex sample data. PMID- 22676505 TI - Number needed to treat and cost-effectiveness in the prevention of ventilator associated pneumonia. PMID- 22676506 TI - Perioperative confocal microscopy of the nail matrix in the management of in situ or minimally invasive subungual melanomas. AB - BACKGROUND: Although dermoscopy of the nail plate is helpful to discriminate between benign and malignant causes of nail pigmentations, there remain ambiguous cases in which a matricial biopsy is required. When a subungual melanoma is diagnosed histopathologically, a complementary surgical treatment is performed secondarily, the duration of postoperative disability being accordingly prolongated. OBJECTIVES: The purpose of our study was to evaluate the feasibility of an intraoperative diagnosis by reflectance confocal microscopy (RCM). PATIENTS AND METHODS: Our series included nine consecutive patients who underwent a matricial biopsy for an acquired melanonychia (one benign lentigo and eight melanomas). RCM examination was performed in vivo on the nail matrix after reclination of the nail plate, and/or ex vivo on the fresh tissue biopsy. RCM data were compared with histopathology. RESULTS: There was a good correlation between confocal and histopathological features. Seven melanoma cases were unequivocally diagnosed intraoperatively according to the confocal features, whereas the lentigo was correctly classified as a benign lesion according to RCM. The remaining lesion could not be unequivocally classified by RCM and corresponded histopathologically to an early melanoma that required immunostaining to be diagnosed. CONCLUSIONS: Intraoperative RCM examination of the nail matrix is an efficient diagnostic approach of melanonychia striata that permits an extemporaneous diagnosis of malignancy and therefore a one-step surgical treatment of in situ or minimally invasive melanoma, reducing dramatically the duration of postoperative disability. PMID- 22676507 TI - Comparative proteomics between natural Microcystis isolates with a focus on microcystin synthesis. AB - BACKGROUND: Microcystis aeruginosa is a species of cyanobacteria commonly found in a number of countries and frequently related to animal poisoning episodes due to its capacity to produce the cyanotoxin known as microcystin. Despite vast literature on microcystin structures and their deleterious effects, little is known about its synthesis by cyanobacteria. Therefore, this study used proteomic tools to compare two M. aeruginosa strains, contrasting them for microcystin production. RESULTS: 2-DE gels were performed and 30 differential protein spots were chosen. Among them, 11 protein spots were unique in the toxin producing strain and 8 in the non-toxin producing strain, and 14 protein spots were shown on both 2-DE gels but expressed differently in intensity. Around 57% of the tandem mass spectrometry identified proteins were related to energy metabolism, with these proteins being up-regulated in the toxin producing strain. CONCLUSIONS: These data suggest that the presence of higher quantities of metabolic enzymes could be related to microcystin metabolism in comparison to the non-toxin producing strain. Moreover, it was suggested that the production of microcystin could also be related to other proteins than those directly involved in its production, such as the enzymes involved in the Calvin cycle and glycolysis. PMID- 22676508 TI - The evolution of prenatal screening and diagnosis and its impact on an unselected population over an 18-year period. AB - OBJECTIVE: To review changes in and impact of prenatal screening and diagnosis. DESIGN: Population-based congenital anomaly register study. SETTING: Oxfordshire. POPULATION: Congenital anomalies confirmed and those suspected prenatally, delivered 1991-2008. METHODS: Analysis of proportions of congenital anomalies confirmed and those suspected prenatally. MAIN OUTCOME MEASURES: Birth prevalence, prenatal detection rates, pregnancy outcomes. RESULTS: A total of 2651 (2.3%) infants/fetuses had a congenital anomaly diagnosed. There were 3839 suspected or confirmed cases, 2847 due to a prenatal suspicion, of which 1659 had an anomaly confirmed at delivery, and 1188 false-positive diagnoses, 91% due to reporting ultrasound normal variants. The percentage of prenatal notifications rose from 48% in 1991-93 to 83-88% from 1996 to 2003 and dropped to 61% in 2006 08, partly reflecting changes in the reporting of normal variants. Reporting these increased the prenatal diagnosis rate from 53 to 63% with an increase in false-positive rate from 0.09 to 1.04%. A total of 722 (44% of prenatally detected affected fetuses) resulted in termination; 48% of these had chromosome anomalies, 34% had isolated structural anomalies, 7% had multiple anomalies, 10% had familial disorders; 42% had lethal anomalies and 58% would probably have survived the neonatal period giving an estimated 20% reduction in birth prevalence of congenital anomalies compatible with survival because of terminations. CONCLUSION: There has been an improvement in prenatal detection of congenital anomalies over the two decades studied. The recognition that reporting normal variants, although increasing prenatal detection rates, leads to an increase in false-positive diagnoses has had an impact on practice that has redressed the balance between these two effects. PMID- 22676509 TI - Inter-relationships between the economic and emotional consequences of colorectal cancer for patients and their families: a qualitative study. AB - BACKGROUND: While the evidence-base concerning the economic impact of cancer for patients and their families/carers has grown in recent years, there is little known about how emotional responses to cancer influence this economic impact. We investigated the economic costs of cancer in the context of patients' emotions and how these both shaped the patient and family burden. METHODS: Health professionals from six hospitals invited patients diagnosed with colorectal cancer (ICD10 C18-C20) within the previous year to take part in the study. Semi structured face-to-face interviews were conducted with patients and, where available, a family member. Interviews covered medical and non-medical costs incurred as a result of cancer and the impact of these on the lives of the patient and their family. Interviews were audio-recorded. Recordings were transcribed verbatim and these data were analysed qualitatively using thematic content analysis. RESULTS: Twenty-two patients with colorectal cancer (17 colon and 5 rectal; 14 women and 8 men) were interviewed; 6 were accompanied by a family member. Important cancer-related financial outlays included: travel and parking associated with hospital appointments; costs of procedures; increased household bills; and new clothing. Cancer impacted on employed individuals' ability to work and depressed their income. The opportunity cost of informal care for carers/family members, especially immediately post-diagnosis, was a strong theme. All patients spoke of the emotional burden of colorectal cancer and described how this burden could lead to further costs for themselves and their families by limiting work and hindering their ability to efficiently manage their expenses. Some patients also spoke of how economic and emotional burdens could interact with each other. Support from employers, family/carers and the state/health services and patients' own attitudes influenced this inter relationship. CONCLUSIONS: The economic impact of colorectal cancer on patients and their families is complex. This study suggests that the economic costs and the emotional impact of cancer are often related and can exacerbate each other, but that various factors can meditate this inter-relationship. PMID- 22676510 TI - Pathobiology of cancer metastasis: a short account. AB - Cancer-initiating cells display aberrant functional and phenotypic characteristics of normal stem cells from which they evolved by accumulation of multiple cytogenetic and/or epigenetic alterations. Signal transduction pathways which are essential for normal stem cell function are abnormally expressed by cancer cells, with a cancer cell phenotype playing an essential role in cancerization and metastasis.Local tumour progression, metastasis and metastatic tumour growth are mediated by direct cell-to-cell and paracrine reciprocal interactions between cancer cells and various stromal cells including fibroblasts, macrophages, bone marrow derived stem cells and progenitor cells. These interactions mediate breakdown of basement membrane barriers and angiogenesis both locally at the invasive front of the primary tumour and at the distant metastatic site; attract primary tumour cells to the candidate metastatic site; and promote proliferation, survival and growth of primary tumour cells and of metastatic cells at their distant site.It is the purpose of this article to highlight the analogies between some of the genetic programs of normal stem cells, and of cancer cells participating in the process of metastasis. PMID- 22676511 TI - Spray coating as a powerful technique in preparation of solid dispersions with enhanced desloratadine dissolution rate. AB - Solid dispersion systems have been widely used to enhance dissolution rate and oral bioavailability of poorly water-soluble drugs. However, the formulation process development and scale-up present a number of difficulties which has greatly limited their commercial applications. In this study, solid dispersions (SDs) of desloratadine (DSL) with povidone (PVP) and crospovidone (cPVP) were prepared by spray coating technique. The process involved the spray application of 96% ethanol solution of DSL and PVP/cPVP, and subsequent deposition of the coprecipitates onto microcrystalline cellulose pellets during drying by air flow in a mini spray coater. The results from the present study demonstrated that the spray coating process is efficient in preparing SDs with enhanced drug dissolution rate and it is highly efficient in organic solvent removal. Both PVP and cPVP greatly improved drug dissolution rate by SDs, with PVP showing better solubilization capability. Very fast drug dissolution rate is achieved from SDs containing PVP regardless of differences in K grade. SD with smaller particles of cPVP have higher drug dissolution rate in comparison to the cPVP with larger particles. Results from physical state characterization indicate that DSL in SDs exist in the amorphous (high free-energy) state which is probably stabilized by PVP/cPVP. After 6-month accelerated stability study, DSL remains amorphous, while PVP and cPVP act as anti-plasticizing agents, offering efficient steric hindrance for nucleation and crystal growth. PMID- 22676548 TI - Effects of job-related stress and burnout on asthenopia among high-tech workers. AB - Eye- and vision-related symptoms are the most frequent health problems among computer users. The findings of eye strain, tired eyes, eye irritation, burning sensation, redness, blurred vision and double vision, when appearing together, have recently been termed 'computer vision syndrome', or asthenopia. To examine the frequency and intensity of asthenopia among individuals employed in research and development departments of high-tech firms and the effects of job stress and burnout on ocular complaints, this study included 106 subjects, 42 high-tech workers (study group) and 64 bank employees (control group). All participants completed self-report questionnaires covering demographics, asthenopia, satisfaction with work environmental conditions, job-related stress and burnout. There was a significant between-group difference in the intensity of asthenopia, but not in its frequency. Burnout appeared to be a significant contributing factor to the intensity and frequency of asthenopia. This study shows that burnout is a significant factor in asthenopic complaints in high-tech workers. PRACTITIONER SUMMARY: This manuscript analyses the effects of psychological environmental factors, such as job stress and burnout, on ocular complaints at the workplace of computer users. The findings may have an ergonomic impact on how to improve health, safety and comfort of the working environment among computer users, for better perception of the job environment, efficacy and production. PMID- 22676547 TI - Short-term neurodevelopmental outcomes in neonates with congenital heart disease: the era of newer surgical strategies. AB - OBJECTIVE: The objective of this study was to determine neurodevelopmental outcomes up to 30 months of age in a cohort of neonates requiring surgical intervention without circulatory arrest for congenital heart disease and to correlate these outcomes with characteristics detected prior to hospital discharge. DESIGN AND SETTING: An observational cohort of surviving neonates who underwent surgical intervention without circulatory arrest for congenital heart disease between 2002 and 2003 was studied at a single tertiary care institution. PATIENTS: Thirty-five patients were followed from 4 to 6 months of age until 24 30 months of age. OUTCOME MEASURES: Neuromotor abnormalities, use of special services, and degree of developmental delay at set intervals between 4 and 30 months of age were retrospectively obtained from clinical reports. The relationship between these outcomes and clinical characteristics prior to hospital discharge was analyzed. RESULTS: Those with neuromotor abnormalities prior to discharge were likely to have persistent abnormalities in muscle strength, tone, and symmetry until 4-6 months of age, odds ratio 6 (1.3-29). By 24-30 months of age, motor abnormalities or developmental delay occurred in 10 of 20 infants (50%), but were no longer significantly associated with predischarge findings. CONCLUSIONS: Infants undergoing surgical intervention for congenital heart disease are at risk for neurodevelopmental abnormalities, which may not become apparent until months after hospital discharge. Early impairment may also resolve over time. Close developmental follow-up in this high-risk cohort of patients is warranted. PMID- 22676549 TI - Impact of alleles at the Yellow Burley (Yb) loci and nitrogen fertilization rate on nitrogen utilization efficiency and tobacco-specific nitrosamine (TSNA) formation in air-cured tobacco. AB - Tobacco-specific nitrosamine (TSNA) formation in tobacco is influenced by alkaloid levels and the availability of nitrosating agents. Tobacco types differ in their potential for TSNA accumulation due to genetic, agronomic, and curing factors. Highest TSNA concentrations are typically measured in burley tobaccos. One of the main genetic differences between burley and all other tobacco types is that this tobacco type is homozygous for recessive mutant alleles at the Yellow Burley 1 (Yb(1)) and Yellow Burley 2 (Yb(2)) loci. In addition, burley tobacco is typically fertilized at higher nitrogen (N) rates than most other tobacco types. This study utilized nearly isogenic lines (NILs) differing for the presence of dominant or recessive alleles at the Yb(1) and Yb(2) loci to investigate the potential influence of genes at these loci on TSNA accumulation. Three pairs of NILs were evaluated at three different nitrogen fertilization rates for alkaloid levels, nitrogen physiology measures, and TSNA accumulation after air-curing. As previously observed by others, positive correlations were observed between N application rates and TSNA accumulation. Recessive alleles at Yb(1) and Yb(2) were associated with increased alkaloid levels, reduced nitrogen use efficiency, reduced nitrogen utilization efficiency, and increased leaf nitrate nitrogen (NO(3)-N). Acting together, these factors contributed to significantly greater TSNA levels in genotypes possessing the recessive alleles at these two loci relative to those carrying the dominant alleles. The chlorophyll-deficient phenotype conferred by the recessive yb(1) and yb(2) alleles probably contributes in a substantial way to increase available NO(3)-N during curing and, consequently, increased potential for TSNA formation. PMID- 22676550 TI - Temperature effect on the two-photon absorption spectrum of all-trans-beta carotene. AB - In this report, we investigate the influence of temperature on the two-photon absorption (2PA) spectrum of all-trans-beta-carotene using the femtosecond white light-continuum Z-scan technique. We observed that the 2PA cross-section decreases quadratically with the temperature. Such effect was modeled using a three-energy-level diagram within the sum-over-essential states approach, assuming temperature dependencies to the transition dipole moment and refractive index of the solvent. The results show that the transition dipole moments from ground to excited state and between the excited states, which governed the two photon matrix element, have distinct behaviors with the temperature. The first one presents a quadratic dependence, while the second exhibits a linear dependence. Such effects were attributed mainly to the trans->cis thermal interconversion process, which decreases the effective conjugation length, contributing to diminishing the transition dipole moments and, consequently, the 2PA cross-section. PMID- 22676552 TI - Genome-wide characterization of Vibrio phage phipp2 with unique arrangements of the mob-like genes. AB - BACKGROUND: Vibrio parahaemolyticus is associated with gastroenteritis, wound infections, and septicemia in human and animals. Phages can control the population of the pathogen. So far, the only one reported genome among giant vibriophages is KVP40: 244,835 bp with 26% coding regions that have T4 homologs. Putative homing endonucleases (HE) were found in Vibrio phage KVP40 bearing one segD and Vibrio cholerae phage ICP1 carrying one mobC/E and one segG. RESULTS: A newly isolated Vibrio phage phipp2, which was specific to the hosts of V. parahaemolyticus and V. alginolyticus, featured a long nonenveloped head of ~90 * 50 nm and tail of ~110 nm. The phage can survive at 50 degrees C for more than one hour. The genome of the phage phipp2 was sequenced to be 246,421 bp, which is 1587 bp larger than KVP40. 383 protein-encoding genes (PEGs) and 30 tRNAs were found in the phage phipp2. Between the genomes of phipp2 and KVP40, 254 genes including 29 PEGs for viral structure were of high similarity, whereas 17 PEGs of KVP40 and 21 PEGs of phipp2 were unmatched. In both genomes, the capsid and tail genes have been identified, as well as the extensive representation of the DNA replication, recombination, and repair enzymes. In addition to the three giant indels of 1098, 1143 and 3330 nt, phipp2 possessed unique proteins involved in potassium channel, gp2 (DNA end protector), tRNA nucleotidyltransferase, and mob type HEs, which were not reported in KVP40. The phipp2 PEG274, with strong promoters and translational initiation, was identified to be a mobE type, flanked by NrdA and NrdB/C homologs. Coincidently, several pairs of HE-flanking homologs with empty center were found in the phages of Vibrio phages phipp2 and KVP40, as well as in Aeromonas phages (Aeh1 and Ae65), and cyanophage P-SSM2. CONCLUSIONS: Vibrio phage phipp2 was characterized by morphology, growth, and genomics with three giant indels and different types of HEs. The gene analysis on the required elements for transcription and translation suggested that the phipp2 PEG274 was an active mobE gene. The phage was signified to be a new species of T4-related, differing from KVP40. PMID- 22676551 TI - Clinicopathologic features and treatment outcomes of patients with human epidermal growth factor receptor 2-positive adenocarcinoma of the esophagus and gastroesophageal junction. AB - Human epidermal growth factor receptor 2 (HER2) is overexpressed in 21% of gastric and 33% of gastroesophageal junction (GEJ) adenocarcinomas. Trastuzumab has been approved for metastatic HER2-positive gastric/GEJ cancer in combination with chemotherapy. This retrospective analysis was undertaken to better define the clinicopathologic features, treatment outcomes, and prognosis in patients with HER2-positive adenocarcinoma of the esophagus/GEJ. Pathologic specimens from 156 patients with adenocarcinoma of the esophagus/GEJ treated on clinical trials with chemoradiation and surgery were tested for HER2. Seventy-six patients also received 2 years of gefitinib. Baseline characteristics and treatment outcomes of the HER2-positive and negative patients were compared both in aggregate and separately for each of the two trials. Of 156 patients, 135 had sufficient pathologic material available for HER2 assessment. HER2 positivity was found in 23%; 28% with GEJ primaries and 15% with esophageal primaries (P= 0.10). There was no statistical difference in clinicopathologic features between HER2-positive and negative patients except HER2-negative tumors were more likely to be poorly differentiated (P < 0.001). Locoregional recurrence, distant metastatic recurrence, any recurrence, and overall survival were also statistically similar between the HER2-positive and the HER2-negative groups, in both the entire cohort and in the gefitinib-treated subset. Except for tumor differentiation, HER2 positive and negative patients with adenocarcinoma of the esophagus and GEJ do not differ in clinicopathologic characteristics and treatment outcomes. Given the demonstrated benefit of trastuzumab in HER2-positive gastric cancer and the similar incidence of HER2 overexpression in esophageal/GEJ adenocarcinoma, further evaluation of HER2-directed therapy in this disease seems indicated. PMID- 22676553 TI - Sleep quality and its correlates in patients on continuous ambulatory peritoneal dialysis. AB - OBJECTIVE: The aim of this study was to investigate demographic, clinical and psychosocial factors associated with sleep quality in patients on continuous ambulatory peritoneal dialysis (CAPD). MATERIAL AND METHODS: Demographic data, clinical and biochemical parameters of 112 CAPD patients (convenience sample of 52 women and 60 men, mean age 51 +/- 15 years) were measured. In the same patients, the Pittsburgh Sleep Quality Index (PSQI) was used for assessing sleep quality, the Beck Depression Inventory (BDI) for severity of depressive symptoms, the International Restless Legs Syndrome Study Group criteria for the diagnosis of restless legs syndrome (RLS), and the Short Form-36 (SF-36) of Medical Outcomes Study questionnaire for quality of life (QoL). RESULTS: Patients with PSQI scores of > 5 ("bad sleepers") had lower serum albumin (p = 0.008), total cholesterol (p = 0.034), normalized protein equivalent of nitrogen appearance (p = 0.046) and residual renal function (p = 0.012), but higher serum ferritin (p = 0.016) and BDI scores (p < 0.001). No significant correlation could be demonstrated between sleep quality and other demographic and clinical parameters. Although the prevalence of RLS was higher in poor sleepers, the difference did not reach statistical significance (p = 0.067). In multivariate analysis, only elevated BDI was an independent predictor of poor sleep quality (p = 0.031). Compared with good sleepers, poor sleepers had significantly lower QoL scores in all subscales of the SF-36. CONCLUSIONS: Although poor sleepers had lower nutritional indices, an elevated BDI was the only independent predictor of poor sleep quality. Poor sleep quality was also associated with lower QoL in patients on CAPD. PMID- 22676554 TI - Obstructive uropathy is associated with polyomavirus viremia in pediatric kidney transplantation. AB - BKVN leads to allograft dysfunction following kidney transplantation and is preceded by BK viremia. Studies in pediatric kidney transplant recipients reveal an incidence of viruria ranging from 18% to 33%, viremia 6-16%, and BKVN 2-8%. Specific risk factors have not been clearly elucidated. Retrospective chart review of pediatric kidney transplants performed from January 2005 through December 2009; to identify risk factors associated with BK viremia in pediatric kidney transplant recipients from a single center. Of the 93 patients who received kidney transplants in the study period, 22 (24%) developed BK viruria, including 12 (13%) who developed viremia. One patient with viremia (1.6%) had BKVN. Obstructive uropathy was identified as the cause of ESKD in 22 (24%) of all recipients. 27% (n = 6) of these 22 patients developed viremia, while only 8.5% (6/71) with ESKD from another cause had viremia (p = 0.001). No other examined variable differed between the two groups. Although the overall incidence was no higher than other reported series, we identified that BK disease was more frequent in children with OU. A higher index of suspicion for invasive BK disease is necessary in patients with OU who receive kidney allografts. Transplant protocols may need to consider underlying cause of ESKD when designing screening protocols for BK disease in children after kidney transplantation. PMID- 22676555 TI - The concept of double bundle ACL simulation with a single bundle patellar tendon graft. A cadaveric feasibility study. AB - BACKGROUND: There is significant interest in the restoration of the double-bundle anatomy of the native ACL when performing ACL reconstruction. Possible techniques include those utilizing two separate grafts with independent tunnels and those that attempt to mimic this anatomy with a single graft and fewer tunnels. Many of the latter techniques require specific instrumentation and are technically challenging. We demonstrate that the double-bundle anatomy of the native ACL can theoretically be mimicked by a single-bundle reconstruction. METHODS: We performed single bundle ACL reconstruction with a bone-patellar tendon-bone (BTB) graft in two cadaveric knees. Both grafts were placed to mimic the native ACL footprints - one reconstruction was performed with rectangular bone blocks and oval tunnels and one was performed utilizing a standard BTB graft and round tunnels. Qualitative assessment of graft behavior was made as the knees were taken through a range of motion. RESULTS: The ACL graft was able to qualitatively mimic the behavior of the native ACL in both knees provided the bone blocks were correctly orientated. CONCLUSIONS: ACL reconstruction with a single BTB graft can qualitatively mimic the behavior of the two bundles of the native ACL. The key to ensuring this behavior was noted to be appropriate orientation of the graft in the tunnels. Quantitative biomechanical investigations are necessary to evaluate the impact of graft orientation on function. PMID- 22676556 TI - Combinatorial bulk ceramic magnetoelectric composite libraries of strontium hexaferrite and barium titanate. AB - Bulk ceramic combinatorial libraries were produced via a novel, high-throughput (HT) process, in the form of polycrystalline strips with a gradient composition along the length of the library. Step gradient ceramic composite libraries with 10 mol % steps of SrFe12O19-BaTiO3 (SrM-BT) were made and characterized using HT methods, as a proof of principle of the combinatorial bulk ceramic process, and sintered via HT thermal processing. It was found that the SrM-BT libraries sintered at 1175 degrees C had the optimum morphology and density. The compositional, electrical and magnetic properties of this library were analyzed, and it was found that the SrM and BT phases did not react and remained discrete. The combinatorial synthesis method produced a relatively linear variation in composition. The magnetization of the library followed the measured compositions very well, as did the low frequency permittivity values of most compositions in the library. However, with high SrM content of >=80 mol %, the samples became increasingly conductive, and no reliable dielectric measurements could be made. Such conductivity would also greatly inhibit any ferroelectricity and magnetoelectric coupling with these composites with high levels of the SrM hexagonal ferrite. PMID- 22676557 TI - Patterns of pre-treatment drug abuse, drug treatment history and characteristics of addicts in methadone maintenance treatment in Iran. AB - BACKGROUND: Opiates are the main drugs of abuse, and Methadone Maintenance Treatment (MMT) is the most widely administered drug addiction treatment program in Iran. Our study aimed to investigate patterns of pre-treatment drug abuse, addiction treatment history and characteristics of patients in MMT in Tehran. METHODS: We applied a stratified cluster random sampling technique and conducted a cross-sectional survey utilizing a standard patient characteristic and addiction history form with patients (n = 810) in MMT. The Chi-square test and t test served for statistical analyses. RESULTS: A clear majority of the participants were men (96%), more than 60% of whom were between 25 and 44 years of age, educated (89% had more than elementary education), and employed (>70%). The most commonly reported main drugs of abuse prior to MMT entry were opium (69%) and crystalline heroin (24%). The patients' lifetime drug experience included opium (92%), crystalline heroin (28%), cannabis (16%), amphetamines (15%), and other drugs (33%). Crystalline heroin abusers were younger than opium users, had begun abusing drugs earlier, and reported a shorter history of opiate addiction. CONCLUSION: Opium and crystalline heroin were the main drugs of abuse. A high rate of addiction using more dangerous opiate drugs such as crystalline heroin calls for more preventive efforts, especially among young men. PMID- 22676558 TI - Interventions, policies and evidence: taking an experimental look at international drug control. PMID- 22676559 TI - Popping the balloon effect: assessing drug law enforcement in terms of displacement, diffusion, and the containment hypothesis. AB - The "balloon effect" is an often used but rather dismissive representation of the effects of drug law enforcement. It implies a hydraulic displacement model and an impervious illicit drug trade. This paper reviews theoretical and empirical developments in policing and crime prevention. Based on this, 10 types of displacement are identified and four arguments developed: (1) Displacement is less extensive and harmful than often contended; (2) Where displacement may occur it preferably should be exploited as a policy tool to delay the illicit drug industry and deflect it to less harmful locations and forms; (3) The opposite of displacement occurs, termed a diffusion of drug control benefits, wherein law enforcement has benefits that extend further than envisaged, and has 10 types mirroring those of displacement; (4) The net impact of drug law enforcement is often underestimated, and a containment hypothesis may offer a more accurate framework for evaluation. PMID- 22676560 TI - Substance misuse prevention and economic analysis: challenges and opportunities regarding international utility. AB - Economic analyses of substance misuse prevention assess the intervention cost necessary to achieve a particular outcome, and thereby provide an additional dimension for evaluating prevention programming. This article reviews several types of economic analysis, considers how they can be applied to substance misuse prevention, and discusses challenges to enhancing their international relevance, particularly their usefulness for informing policy decisions. Important first steps taken to address these challenges are presented, including the disease burden concept and the development of generalized cost-effectiveness, advances that facilitate international policy discussions by providing a common framework for evaluating health care needs and program effects. PMID- 22676561 TI - Evaluation of the therapeutic community treatment model in Thailand: policy implications for compulsory and prison-based treatment. AB - This study, conducted in 2005 to 2007, presents results that are based on a proscriptive cohort design. The sample consisted of 769 residents in 22 drug user treatment programs who stayed in treatment for at least 30 days to one year; 510 former residents (66%) from 21 programs (95%) were interviewed again at a 6-month post-treatment follow-up assessment. A majority of the participants were male, lived with family or relatives, had completed only primary school, and had a full time or a part-time job prior to entering treatment. The participating therapeutic community (TC) programs were a mixture of volunteer, compulsory probation, and prison-based programs. In-person interview data and urine testing showed that the self-reported drug use prevalence rates are reliable. The results show large positive treatment effects on 30-day and 6-month illegal drug use and small to medium effects on the severity of alcohol use and related problems. A multilevel regression analysis suggests that residents' reduced stigma, adaptation of the TC model, and frequency of alcohol and drug use-related consequences partially predict treatment success. Study limitations and policy implications are discussed. PMID- 22676562 TI - Harm reduction--from a conceptual framework to practical experience: the example of Germany. AB - Drug demand reduction programs must be integrated into a comprehensive strategy aiming at preventing drug misuse, facilitating access to counseling, to treatment of dependence, and to rehabilitation; and establishing effective measures to reduce the adverse health and social consequences of drug misuse. The continuous and even rising spread of HIV/AIDS and other infectious diseases (e.g., hepatitis B and C) among injecting drug users is alarming. Although, in many countries the prevalence of HIV infections is decreasing due to the implementation of effective harm reduction measures, such as syringe exchange and opiate substitution treatment (OST), in other countries infections are on the rise. The lessons learnt indicate that only a comprehensive, evidence-based approach in prevention, treatment, care, and support is promising in combating the devastating effects of drug dependence. PMID- 22676563 TI - Change is possible: the history of the international drug control regime and implications for future policymaking. AB - The article, based upon an extensive literature review, reconstructs and analyzes the parallel evolution of the international drug control regime and the world opiate market, assessing the impact of the former on the latter until the rise of present-day mass markets. It shows that, since its inception, the regime has focused almost entirely on matters of supply. However, that focus has not always meant "prohibition"; until 1961, the key principle of the regime was "regulation." Given the different forms drug control policy has taken in the past, the authors conclude it may be amenable to new forms in the future. PMID- 22676564 TI - Preventing youthful substance use and harm--between effectiveness and political wishfulness. AB - Drinking, smoking, and drug use are symbolic behaviors for young people, often involving a claim for adult status, and set against a "social clock" of expectations about appropriate behavior for a given age. Use is set in a social world of youth sociability, which young people strive to control themselves. Hence, it is difficult to prevent or delay use through adult-run institutions such as schools. Youth-oriented prevention initiatives succeed best when in tune with general social trends, so that youth cannot so easily feel hypocritically singled out. Regulatory approaches that apply to all have had some success in limiting and shaping youthful use and problems. Well-evaluated trials of efforts to insulate youthful use from harm are needed. PMID- 22676565 TI - Revisiting the concepts of risk and protective factors for understanding the etiology and development of substance use and substance use disorders: implications for prevention. AB - Over the past 20 years we have accumulated a greater knowledge and understanding of the genetic, neurobiological, and behavioral factors that may be associated with young people initiating the use of drugs and other substances and to progressing from use to abuse and dependence. This knowledge suggests that individuals may be "predisposed" to substance use disorders (SUD) and that the actual engagement in these behaviors depends on their environmental experiences from micro to macro levels. This paper summarizes this knowledge base and supports a developmental framework that examines the interaction of posited genetic, psychological, and neurobiological "predispositions" to SUD and those environmental influences that exacerbate this vulnerability. PMID- 22676566 TI - Alcohol, tobacco, and prescription drugs: the relationship with illicit drugs in the treatment of substance users. AB - Alcohol, tobacco, prescription drug, and illicit drug use frequently co-occur. This paper reviews the extent of this co-occurrence in both general population samples and clinical samples, and its impact on treatment outcome. We argue that the research base for understanding comorbidity among tobacco, alcohol, prescription, and illicit drugs needs to be broadened. We specifically advocate for: (1) more epidemiological studies of relationships among alcohol, tobacco, and other illicit drug use; and (2) increased research on treatment options that address the problematic use of all of these drugs. PMID- 22676567 TI - Illegal drugs, anti-drug policy failure, and the need for institutional reforms in Colombia. AB - This paper is inspired by two anomalies encountered in the study of the illegal drugs industry. First, despite the very high profits of coca/cocaine and poppy/opium/heroin production, most countries that can produce do not. Why, for example, does Colombia face much greater competition in the international coffee, banana, and other legal product markets than in cocaine? And second, though illegal drugs are clearly associated with violence, why is it that illegal drug trafficking organizations have been so much more violent in Colombia and Mexico than in the rest of the world? The answers to these questions cannot be found in factors external to Colombia (and Mexico). They require identifying the societal weaknesses of each country. To do so, the history of the illegal drugs industry is surveyed, a simple model of human behavior that stresses the conflict between formal (legal) and informal (socially accepted) norms as a source of the weaknesses that make societies vulnerable is formulated. The reasons why there is a wide gap between formal and informal norms in Colombia are explored and the effectiveness of anti-drug policies is considered to explain why they fail to achieve their posited goals. The essay ends with reflections and conclusion on the need for institutional change. PMID- 22676568 TI - Psychiatric co-morbidity and substance use disorders: treatment in parallel systems or in one integrated system? AB - Psychiatric co-morbidity among substance users refers to the simultaneous presence of at least another psychiatric disorder in a person diagnosed with a substance use disorder. Co-morbid patients represent a substantial number of people in treatment and present greater disorder severity from both the clinical and social perspectives than those people diagnosed with only one type of disorder. We present an overview of the current state of the art concerning the choice of site of treatment, the kind of intervention, the length of such treatment, and future goals, aiming to establish a more effective intervention, and finally so as to further improve clinical outcomes. PMID- 22676569 TI - HIV/AIDS and drug use in China--interactions, impacts, and issues. AB - The interrelationships of HIV/AIDS and drug use and misuse result in complex problems that have been addressed by a variety of sociolegal approaches that often are in contrast to evidence-based medical practices proven effective in reducing associated harms. Like other countries struggling to reduce the incidence and consequences of addiction and HIV/AIDS, China is working to improve systems of care and to revise policies toward drug use and misuse and HIV/AIDS. Greater interaction with researchers and clinicians from around the world can foster increased awareness of effective practices and help implement effective strategies to deal with the problems of HIV/AIDS, and addiction. PMID- 22676570 TI - The science and practice of medication-assisted treatments for opioid dependence. AB - This paper briefly reviews the evolution of opioid addiction treatment from humanitarian to scientific and evidence-based, the evidence bases supporting major medication-assisted treatments and adjunctive psychosocial techniques, as well as challenges faced by clinicians and treatment providers seeking to provide those treatments. Attitudes, politics, policy, and financial issues are discussed. PMID- 22676571 TI - Evolution of concept, but not action, in addiction treatment. AB - The Western approach to addiction treatment involves a medical or disease orientation to understanding the onset, course, and management of addiction, and a clinical goal of abstinence or very significant reductions in drug use, usually with a combination of behavioral and pharmacological interventions. Even within this Western approach, and despite several consensually accepted features of addiction, a significant mismatch remains between what this culture has come to accept as the nature of the disease and how that same culture continues to treat the disease. This paper discusses the evolution of these Western concepts over the past decade without a corresponding evolution in the nature, duration, or evaluation standards for addiction treatment. (1) Here, we take the position that continuing care and adaptive treatment protocols, combining behavioral therapies, family and social supports, and, where needed, medications show much promise to address the typically chronic, relapsing, and heterogeneous nature of most cases of serious addiction. By extension, methods to evaluate effectiveness of addiction treatment should focus upon the functional status of patients during the course of their treatment instead of post-treatment, as is the evaluation practice used with most other chronic illnesses. PMID- 22676573 TI - The role of cytokines and adipocytokines in zoledronate-induced acute phase reaction in postmenopausal women with low bone mass. AB - OBJECTIVE: Patients treated with intravenous zoledronate frequently experience an acute phase reaction (APR) characterized by flu-like symptoms and increased levels of inflammatory cytokines. We aimed to define the role of various cytokines/adipocytokines in zoledronate-induced APR and develop a prognostic model for its prediction. PATIENTS AND MEASUREMENTS: Fifty-one postmenopausal women with low bone mass were subjected to zoledronate intravenous infusion. Patients were divided into those who experienced APR (APR+) and those who did not (APR-). APR was clinically defined by body temperature and the visual analogue pain scale for musculoskeletal symptoms. White blood cell count, leucocytic subpopulations, C-reactive protein, interleukin-6, tumour necrosis factor-alpha, visfatin, resistin and leptin were measured before and 48 h following the infusion. The quantitative insulin sensitivity check index (QUICKI) and homoeostasis model of assessment - insulin resistance (HOMA-IR) were calculated to assess insulin sensitivity and resistance, respectively. RESULTS: (APR+) patients were younger and had lower baseline visfatin and higher baseline lymphocytes and phosphate compared with APR- patients. QUICKI decreased and HOMA IR increased in APR+ patients while remained unchanged in APR- patients. In binary logistic regression analysis, a model containing previous bisphosphonate treatment, age, body mass index, lymphocytes and visfatin, which predicted zoledronate-induced APR with 82.1% sensitivity and 73.9% specificity, was selected. In this model, lymphocytes (P = 0.010) and visfatin (P = 0.029) at baseline could independently predict APR. CONCLUSIONS: Zoledronate-induced APR is associated with serum increases of pro-inflammatory cytokines and an increase of insulin resistance. Patients with higher lymphocytes and lower visfatin levels at baseline are at higher risk for APR. PMID- 22676574 TI - Novel genetic linkage of rat Sp6 mutation to Amelogenesis imperfecta. AB - BACKGROUND: Amelogenesis imperfecta (AI) is an inherited disorder characterized by abnormal formation of tooth enamel. Although several genes responsible for AI have been reported, not all causative genes for human AI have been identified to date. AMI rat has been reported as an autosomal recessive mutant with hypoplastic AI isolated from a colony of stroke-prone spontaneously hypertensive rat strain, but the causative gene has not yet been clarified. Through a genetic screen, we identified the causative gene of autosomal recessive AI in AMI and analyzed its role in amelogenesis. METHODS: cDNA sequencing of possible AI-candidate genes so far identified using total RNA of day 6 AMI rat molars identified a novel responsible mutation in specificity protein 6 (Sp6). Genetic linkage analysis was performed between Sp6 and AI phenotype in AMI. To understand a role of SP6 in AI, we generated the transgenic rats harboring Sp6 transgene in AMI (Ami/Ami + Tg). Histological analyses were performed using the thin sections of control rats, AMI, and Ami/Ami + Tg incisors in maxillae, respectively. RESULTS: We found the novel genetic linkage between a 2-bp insertional mutation of Sp6 gene and the AI phenotype in AMI rats. The position of mutation was located in the coding region of Sp6, which caused frameshift mutation and disruption of the third zinc finger domain of SP6 with 11 cryptic amino acid residues and a stop codon. Transfection studies showed that the mutant protein can be translated and localized in the nucleus in the same manner as the wild-type SP6 protein. When we introduced the CMV promoter-driven wild-type Sp6 transgene into AMI rats, the SP6 protein was ectopically expressed in the maturation stage of ameloblasts associated with the extended maturation stage and the shortened reduced stage without any other phenotypical changes. CONCLUSION: We propose the addition of Sp6 mutation as a new molecular diagnostic criterion for the autosomal recessive AI patients. Our findings expand the spectrum of genetic causes of autosomal recessive AI and sheds light on the molecular diagnosis for the classification of AI. Furthermore, tight regulation of the temporospatial expression of SP6 may have critical roles in completing amelogenesis. PMID- 22676576 TI - COST Action BM0602: a European network to combat obesity and the metabolic syndrome. PMID- 22676575 TI - Potential immunological consequences of pharmacological suppression of gastric acid production in patients with multiple sclerosis. AB - Corticosteroids are standard treatment for patients with multiple sclerosis experiencing acute relapse. Because dyspeptic pain is a common side effect of this intervention, patients can be given a histamine receptor-2 antagonist, proton pump inhibitor or antacid to prevent or ameliorate this disturbance. Additionally, patients with multiple sclerosis may be taking these medications independent of corticosteroid treatment. Interventions for gastric disturbances can influence the activation state of the immune system, a principal mediator of pathology in multiple sclerosis. Although histamine release promotes inflammation, activation of the histamine receptor-2 can suppress a proinflammatory immune response, and blocking histamine receptor-2 with an antagonist could shift the balance more towards immune stimulation. Studies utilizing an animal model of multiple sclerosis indicate that histamine receptor 2 antagonists potentially augment disease activity in patients with multiple sclerosis. In contrast, proton pump inhibitors appear to favor immune suppression, but have not been studied in models of multiple sclerosis. Antacids, histamine receptor-2 antagonists and proton pump inhibitors also could alter the intestinal microflora, which may indirectly lead to immune stimulation. Additionally, elevated gastric pH can promote the vitamin B12 deficiency that patients with multiple sclerosis are at risk of developing. Here, we review possible roles of gastric acid inhibitors on immunopathogenic mechanisms associated with multiple sclerosis. PMID- 22676577 TI - Development and analysis of acceptance of a nutrition education package among a rural elderly population: an action research study. AB - BACKGROUND: It is well known that older adults are often vulnerable to malnutrition. This action research was conducted to develop a nutrition education package for promoting healthy ageing and reducing risk of chronic diseases among older adults in a rural area of Malaysia. METHODS: This study was designed and conducted in three stages, including needs assessment, development of the package and analysis of acceptance among 33 older adults aged 60 years and over in rural communities, and 14 health staff members at rural health clinics. Subjects completed a questionnaire including sociodemographic factors and acceptance evaluation of the nutrition education package with respect to content, graphics and design. Data were analysed descriptively using numbers and percentages. RESULTS: A nutrition education package comprising a booklet, flipchart and placemats was developed. A total of 42.4% of the older adults expressed that the sentences in the flipchart needed to be simplified and medical terms explained. Terminology (60%), illustrations (20%) and nutrition recommendations (20%) were the aspects that prevented elderly subjects from fully understanding the booklet. Information on the placemats was easily understood by subjects. CONCLUSIONS: A well accepted nutrition education package for promoting healthy ageing and reducing risk of chronic diseases was developed that incorporated modifications based on feedback from older adult subjects and health clinic staff in a rural area. It is a tool that can effectively be used for health education in this population. PMID- 22676578 TI - The effect of maternal characteristics and gestational diabetes on birthweight. AB - OBJECTIVE: To examine the effect of maternal characteristics, including advancing maternal age, body mass index (BMI), racial origin and development of gestational diabetes mellitus (GDM), on birthweight and the interactions between these factors. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Fifteen maternity units in North West London, between 1988 and 2000. POPULATION: A cohort of 130 549 pregnant women. METHODS: Multivariate regression analysis. OUTCOME MEASURES: Birthweight z-scores in non-GDM and GDM groups within three main racial groups (white European, black and South Asian women). RESULTS: Babies born to women with GDM were heavier compared with those born to women with no GDM in all racial groups. In black women with GDM the birthweight z-scores were 0.805 higher, in South Asian women the scores were 0.618 higher and in white European women the scores were 0.437 higher, compared with the respective non-GDM group (P < 0.001 for both comparisons versus white European women), and these differences were much greater at high rather than at low maternal BMIs. Advancing maternal age, increasing BMI, highest diastolic blood pressure, Castair's index, racial group and presence of GDM or smoking were each, individually, significantly associated with birthweight z-scores (P < 0.001 for all variables). After adjusting for possible confounding factors, BMI was positively associated with birthweight z-scores within all racial groups (P < 0.001 for all), irrespective of glycaemic status, but its effect was much greater in women with GDM, particularly in those of non-White origin. After adjusting for possible confounding factors, advancing maternal age was only positively associated with birthweight in women of white European and South Asian racial origin who did not suffer from GDM (P < 0.001 for both). CONCLUSION: Gestational diabetes mellitus strongly accentuates the effect of maternal BMI on birthweight, especially within non-white populations. PMID- 22676579 TI - Patients with Parkinson's disease are often accompanied with athlete's foot. PMID- 22676580 TI - Goal-directed aimed movements with path obstructions. AB - Studies are reported in which participants moved from a starting position to a final target, but moved around obstacles that prevented a direct path being taken. Seven experiments are reported in which subjects made multiple-component movements, defined by changes in the direction of movement, but without intervening targets (or stopping points) between components. It was found that components of movement time did not interact, contrary to the results of Gan and Hoffmann (1988b) for cases where there was an intervening target, and that component times could be added. For ballistic components, the time for the movement was linearly related to the square root of the total amplitude of movement; for components that were visually controlled, the time was related to Fitts' Index of Difficulty based on the total amplitude of movement and the final target size. Results are compared to data for movements with intervening targets, where the movement integration hypothesis is valid. PRACTITIONER SUMMARY: Many movements, particularly to inaccessible places, cannot be made directly, but must be made about obstacles in the path. This research shows how times for these movements can be quantified in terms of the direct path length and the size and location of the obstacles. PMID- 22676581 TI - Acute myeloid leukemia and transcription factors: role of erythroid Kruppel-like factor (EKLF). AB - We have investigated the role of erythroid transcription factors mRNA expression in patients with acute myeloid leukemia (AML) in the context of cytogenetic and other prognostic molecular markers, such as FMS-like Tyrosine Kinase 3 (FLT3), Nucleophosmin 1 (NPM1), and CCAAT/enhance-binding protein alpha (CEBPA) mutations. Further validation of Erythroid Kruppel-like Factor (EKLF) mRNA expression as a prognostic factor was assessed.We evaluated GATA binding protein 1 (GATA1), GATA binding protein 2 (GATA2), EKLF and Myeloproliferative Leukemia virus oncogen homology (cMPL) gene mRNA expression in the bone marrow of 65 AML patients at diagnosis, and assessed any correlation with NPM1, FLT3 and CEBPA mutations. EKLF-positive AML was associated with lower WBC in peripheral blood (P = 0.049), a higher percentage of erythroblasts in bone marrow (p = 0.057), and secondary AMLs (P = 0.036). High expression levels of EKLF showed a trend to association with T-cell antigen expression, such as CD7 (P = 0.057). Patients expressing EKLF had longer Overall Survival (OS) and Event Free Survival (EFS) than those patients not expressing EKLF (median OS was 35.61 months and 19.31 months, respectively, P = 0.0241; median EFS was 19.80 months and 8.03 months, respectively, P = 0.0140). No correlation of GATA1, GATA2, EKLF and cMPL levels was observed with FLT-3 or NPM1 mutation status. Four of four CEBPA mutated AMLs were EKLF positive versus 10 of 29 CEBPA wild-type AMLs; three of the CEBPA mutated, EKLF-positive AMLs were also GATA2 positive. There were no cases of CEBPA mutations in the EKLF-negative AML group. In conclusion, we have validated EKLF mRNA expression as an independent predictor of outcome in AML, and its expression is not associated with FLT3-ITD and NPM1 mutations. EKLF mRNA expression in AML patients may correlate with dysregulated CEBPA. PMID- 22676582 TI - Activation of Nrf2 is required for up-regulation of the pi class of glutathione S transferase in rat primary hepatocytes with L-methionine starvation. AB - Numerous genes expression is regulated in response to amino acid shortage, which helps organisms adapt to amino acid limitation. The expression of the pi class of glutathione (GSH) S-transferase (GSTP), a highly inducible phase II detoxification enzyme, is regulated mainly by activates activating protein 1 (AP 1) binding to the enhancer I of GSTP (GPEI). Here we show the critical role of nuclear factor erythroid-2-related factor 2 (Nrf2) in up-regulating GSTP gene transcription. Primary rat hepatocytes were cultured in a methionine-restricted medium, and immunoblotting and RT-PCR analyses showed that methionine restriction time-dependently increased GSTP protein and mRNA expression over a 48 h period. Nrf2 translocation to the nucleus, nuclear proteins binding to GPEI, and antioxidant response element (ARE) luciferase reporter activity were increased by methionine restriction as well as by l-buthionine sulfoximine (BSO), a GSH synthesis inhibitor. Transfection with Nrf2 siRNA knocked down Nrf2 expression and reversed the methionine-induced GSTP expression and GPEI binding activity. Chromatin immunoprecipitation assay confirmed the binding of Nrf2 to the GPEI. Phosphorylation of extracellular signal-regulated kinase 2 (ERK2) was increased in methionine-restricted and BSO-treated cells. ERK2 siRNA abolished methionine restriction-induced Nrf2 nuclear translocation, GPEI binding activity, ARE luciferase reporter activity, and GSTP expression. Our results suggest that the up-regulation of GSTP gene transcription in response to methionine restriction likely occurs via the ERK-Nrf2-GPEI signaling pathway. PMID- 22676583 TI - Chromium isotope fractionation during reduction of Cr(VI) under saturated flow conditions. AB - Chromium isotopes are potentially useful indicators of Cr(VI) reduction reactions in groundwater flow systems; however, the influence of transport on Cr isotope fractionation has not been fully examined. Laboratory batch and column experiments were conducted to evaluate isotopic fractionation of Cr during Cr(VI) reduction under both static and controlled flow conditions. Organic carbon was used to reduce Cr(VI) in simulated groundwater containing 20 mg L(-1) Cr(VI) in both batch and column experiments. Isotope measurements were performed on dissolved Cr on samples from the batch experiments, and on effluent and profile samples from the column experiment. Analysis of the residual solid-phase materials by scanning electron microscopy (SEM) and by X-ray absorption near edge structure (XANES) spectroscopy confirmed association of Cr(III) with organic carbon in the column solids. Decreases in dissolved Cr(VI) concentrations were coupled with increases in delta(53)Cr, indicating that Cr isotope enrichment occurred during reduction of Cr(VI). The delta(53)Cr data from the column experiment was fit by linear regression yielding a fractionation factor (alpha) of 0.9979, whereas the batch experiments exhibited Rayleigh-type isotope fractionation (alpha = 0.9965). The linear characteristic of the column delta(53)Cr data may reflect the contribution of transport on Cr isotope fractionation. PMID- 22676584 TI - Burial effects of organic coatings on the heterogeneous reactivity of particle borne benzo[a]pyrene (BaP) toward ozone. AB - With an aerosol flow tube coupled to an Aerodyne aerosol mass spectrometer (AMS), room temperature (296 +/- 3 K) kinetics studies have been performed on the reaction of gas-phase ozone with benzo[a]pyrene (BaP) adsorbed in submonolayer amounts to dry ammonium sulfate (AS) particles. Three organic substances, i.e., bis(2-ethylhexyl)sebacate (BES, liquid), phenylsiloxane oil (PSO, liquid), and eicosane (EC, solid), were used to coat BaP-AS particles to investigate the effects of such organic coatings on the heterogeneous reactivity of PAHs toward ozone. All the reactions of particle-borne BaP with excess ozone exhibit pseudo first-order kinetics in terms of BaP loss, and reactions with a liquid organic coating proceed by the Langmuir-Hinshelwood (L-H) mechanism. Liquid organic coatings did not significantly affect the kinetics, consistent with the ability of reactants to rapidly diffuse through the organic coating. In contrast, the heterogeneous reactivity of BaP was reduced substantially by a thin (4-8 nm), solid EC coating and entirely suppressed by thick (10-80 nm) coatings, presumably because of slow diffusion through the organic layer. Although the heterogeneous reactivity of surface-bound PAHs is extremely rapid in the atmosphere, this work is the first to experimentally demonstrate a mechanism by which the lifetime of PAHs may be significantly prolonged, permitting them to undergo long-range transport to remote locations. PMID- 22676622 TI - Clinical outcome of endoscopic mucosal resection for esophageal squamous cell cancer invading muscularis mucosa and submucosal layer. AB - When a tumor invades the muscularis mucosa and submucosal layer (T1a-MM and T1b in Japan), esophageal squamous cell cancer poses 10-50% risk of lymph node metastasis. By this stage of esophageal cancer, surgery, although very invasive, is the standard radical therapy for the patients. Endoscopic mucosal resection (EMR) is the absolutely curable treatment for cancer in the superficial mucosal layer. Because of its minimal invasiveness, the indications of EMR may be expanded to include the treatment of T1a-MM and T1b esophageal carcinoma. To date, the clinical outcomes of EMR for T1a-MM and T1b patients have not been fully elucidated. Here, the retrospective analysis of the clinical outcomes is reported. Between January 1994 and December 2007, 247 patients underwent EMR at Kanagawa Cancer Center. Of these individuals, 44 patients with 44 lesions fulfilled the following criteria: (i) extended EMR treatment for clinical T1a-MM and T1b tumor; (ii) diagnosis of clinical N0M0; and (iii) follow up for at least 1 year, and negative vertical margin. These patients were reviewed for their clinical features and outcomes. Statistical analyses were performed by the Kaplan Meier methods, the Chi-square test, and the Cox proportional hazard model. P value of <0.05 was considered statistically significant. The data were analyzed in February 2009. Based on the informed consent and their general health conditions, 44 patients decided the following treatments immediately after the EMR: 2 underwent surgery, 1 underwent adjuvant chemotherapy, and 41 selected follow up without any additional therapy. Of the 41 patients, 20 selected this course by choice, 12 because of severe concurrent diseases, 2 because of poor performance status, and 7 because of other multiple primary cancers. Twelve patients died; two were cause specific (4.5%), eight from multiple primary cancers, one from severe concurrent diseases, and one from unknown causes. No critical complications were noted. Median follow-up time was 51 months (12-126). Five patients ultimately developed lymph node metastasis. One patient with adjuvant chemotherapy required surgery, and another was treated with chemotherapy whose subsequent death was cause specific. The other three patients received chemoradiotherapy and have not shown cause-specific death. Overall and cause specific survival rates at 5 years were 67.3% and 91.8%, respectively. Among 41 patients treated by EMR alone, only one died from primary esophageal cancer (2.4%), and overall and cause-specific survival rates at 5 years were 75.6% and 97.6%, respectively. Multivariate analysis revealed that severe concurrent diseases including multiple primary cancers and the administration of 5 fluorouracil-based chemotherapy for multiple primary cancers significantly influenced survival (P= 0.025, hazard ratio [HR] 13.1 [95% confidence interval 1.5-114]) and (P= 0.037, HR 0.213 [95% confidence interval 0.05-0.914]), respectively. Eight and six patients developed metachronous esophageal squamous cell cancer and local recurrence, respectively. With the exception of one patient, they could be retreated endoscopically. EMR is a reasonable option for the patients with T1a-MM and T1b esophageal carcinoma without clinical metastasis, especially for the individuals with severe concurrent diseases. The prognostic factors for the benefit of EMR in such cases should be further examined. PMID- 22676585 TI - Probing the Xenopus laevis inner ear transcriptome for biological function. AB - BACKGROUND: The senses of hearing and balance depend upon mechanoreception, a process that originates in the inner ear and shares features across species. Amphibians have been widely used for physiological studies of mechanotransduction by sensory hair cells. In contrast, much less is known of the genetic basis of auditory and vestibular function in this class of animals. Among amphibians, the genus Xenopus is a well-characterized genetic and developmental model that offers unique opportunities for inner ear research because of the amphibian capacity for tissue and organ regeneration. For these reasons, we implemented a functional genomics approach as a means to undertake a large-scale analysis of the Xenopus laevis inner ear transcriptome through microarray analysis. RESULTS: Microarray analysis uncovered genes within the X. laevis inner ear transcriptome associated with inner ear function and impairment in other organisms, thereby supporting the inclusion of Xenopus in cross-species genetic studies of the inner ear. The use of gene categories (inner ear tissue; deafness; ion channels; ion transporters; transcription factors) facilitated the assignment of functional significance to probe set identifiers. We enhanced the biological relevance of our microarray data by using a variety of curation approaches to increase the annotation of the Affymetrix GeneChip((r)) Xenopus laevis Genome array. In addition, annotation analysis revealed the prevalence of inner ear transcripts represented by probe set identifiers that lack functional characterization. CONCLUSIONS: We identified an abundance of targets for genetic analysis of auditory and vestibular function. The orthologues to human genes with known inner ear function and the highly expressed transcripts that lack annotation are particularly interesting candidates for future analyses. We used informatics approaches to impart biologically relevant information to the Xenopus inner ear transcriptome, thereby addressing the impediment imposed by insufficient gene annotation. These findings heighten the relevance of Xenopus as a model organism for genetic investigations of inner ear organogenesis, morphogenesis, and regeneration. PMID- 22676623 TI - Metalloprotease (ADAM12-S) as a predictor of preeclampsia: correlation with severity, maternal complications, fetal outcome, and Doppler parameters. AB - OBJECTIVES: To compare the first trimesteric serum level of ADAM12-S in women who developed mild and severe preeclampsia and in healthy gravidas and to correlate these changes with the severity of the disease, maternal complications, fetal outcome, and Doppler cerebroplacental ratio (CPR). DESIGN: Comparative prospective observational study. SETTING: University hospital. METHODS: Serum samples were obtained from 414 women in their first trimester, of which 259 women completed their pregnancy without complications and 155 women developed preeclampsia later in their pregnancies. All were subjected to history taking, examination, laboratory investigations, obstetric ultrasound, and Doppler CPR. RESULTS: ADAM12-S was significantly decreased in patients with severe and in mild preeclampsia compared with the controls. Moreover, there was strong negative correlation with disseminated intravascular coagulopathy (DIC) and HELLP syndrome, cesarean delivery, postpartum hemorrhage, and neonatal intensive care unit admission. ADAM12-S had medium negative correlation with systolic blood pressure and diastolic blood pressure, accidental hemorrhage, cesarean hysterectomy, prematurity, and low birth weight. In addition, it had a weak negative correlation with intracranial hemorrhage, residual hypertension, and intrauterine fetal death. ADAM12-S had strong positive correlation with CPR. There were no correlation with eclampsia, intrauterine growth retardation, acute pulmonary edema, and acute renal failure. CONCLUSION: ADAM12-S is significantly decreased in severe and mild preeclampsia and is correlated with CPR, severity of preeclampsia, maternal complications, and fetal outcome. It is recommended to measure ADAM12-S in the first trimester to predict maternal complications and fetal outcome in pregnancies complicated by preeclampsia. PMID- 22676625 TI - Consumer trophic diversity as a fundamental mechanism linking predation and ecosystem functioning. AB - 1. Primary production and decomposition, two fundamental processes determining the functioning of ecosystems, may be sensitive to changes in biodiversity and food web interactions. 2. The impacts of food web interactions on ecosystem functioning are generally quantified by experimentally decoupling these linked processes and examining either primary production-based (green) or decomposition based (brown) food webs in isolation. This decoupling may strongly limit our ability to assess the importance of food web interactions on ecosystem processes. 3. To evaluate how consumer trophic diversity mediates predator effects on ecosystem functioning, we conducted a mesocosm experiment and a field study using an assemblage of invertebrates that naturally co-occur on North Atlantic coastal saltmarshes. We measured the indirect impact of predation on primary production and leaf decomposition as a result of prey communities composed of herbivores alone, detritivores alone or both prey in combination. 4. We find that primary consumers can influence ecosystem process rates not only within, but also across green and brown sub-webs. Moreover, by feeding on a functionally diverse consumer assemblage comprised of both herbivores and detritivores, generalist predators can diffuse consumer effects on decomposition, primary production and feedbacks between the two processes. 5. These results indicate that maintaining functional diversity among primary consumers can alter the consequences of traditional trophic cascades, and they emphasize the role of the detritus-based sub-web when seeking key biotic drivers of plant production. Clearly, traditional compartmentalization of empirical food webs can limit our ability to predict the influence of food web interactions on ecosystem functioning. PMID- 22676624 TI - Development of a luciferase-based reporter of transcriptional gene silencing that enables bidirectional mutant screening in Arabidopsis thaliana. AB - BACKGROUND: Cytosine methylation is an important chromatin modification that maintains genome integrity and regulates gene expression through transcriptional gene silencing. Major players in de novo methylation guided by siRNAs (known as RNA-directed DNA methylation, or RdDM), maintenance methylation, and active demethylation have been identified in Arabidopsis. However, active demethylation only occurs at a subset of RdDM loci, raising the question of how the homeostasis of DNA methylation is achieved at most RdDM loci. To identify factors that regulate the levels of cytosine methylation, we aimed to establish a transgenic reporter system that allows for forward genetic screens in Arabidopsis. RESULTS: We introduced a dual 35 S promoter (d35S) driven luciferase reporter, LUCH, into Arabidopsis and isolated a line with a moderate level of luciferase activity. LUCH produced transgene-specific 24 nucleotide siRNAs and its d35S contained methylated cytosine in CG, CHG and CHH contexts. Treatment of the transgenic line with an inhibitor of cytosine methylation de-repressed luciferase activity. Mutations in several components of the RdDM pathway but not the maintenance methylation genes resulted in reduced d35S methylation, especially CHH methylation, and de-repression of luciferase activity. A mutation in MOM1, which is known to cooperate with RdDM to silence transposons, reduced d35S DNA methylation and de-repressed LUCH expression. A mutation in ROS1, a cytosine demethylation enzyme, increased d35S methylation and reduced LUCH expression. CONCLUSION: We developed a luciferase-based reporter, LUCH, which reports both DNA methylation directed by small RNAs and active demethylation by ROS1 in Arabidopsis. The moderate basal level of LUCH expression allows for bi directional genetic screens that dissect the mechanisms of DNA methylation as well as demethylation. PMID- 22676626 TI - The data management of a phase III efficacy trial of an 11-valent pneumococcal conjugate vaccine and related satellite studies conducted in the Philippines. AB - BACKGROUND: A large phase III placebo-controlled, randomized efficacy trial of an investigational 11-valent pneumococcal conjugate vaccine against pneumonia in children less than 2 years of age was conducted in the Philippines from July 2000 to December 2004. Clinical data from 12,194 children who were given either study vaccine or placebo was collected from birth up to two years of age for the occurrence of radiologically proven pneumonia as the primary endpoint, and for clinical pneumonia and invasive pneumococcal disease as the secondary endpoints. Several tertiary endpoints were also explored. Along the core trial, several satellite studies on herd immunity, cost-effectiveness of the study vaccine, acute otitis media, and wheezing were conducted. RESULTS: We describe here in detail how the relevant clinical records were managed and how quality control procedures were implemented to ensure that valid data were obtained respectively for the core trial and for the satellite studies. We discuss how the task was achieved, what the challenges were and what might have been done differently. CONCLUSIONS: There were several factors that made the task of data management doable and efficient. First, a pre-trial data management system was available. Secondly, local committed statisticians, programmers and support staff were available and partly familiar to clinical trials. Thirdly, the personnel had undergone training during trial and grew with the task they were supposed to do. Thus the knowledge needed to develop and operate clinical data system was fully transferred to local staff. TRIAL REGISTRATION: Current Controlled Trials ISRCTN62323832. PMID- 22676627 TI - Functional critical aortic stenosis with transient retrograde flow in a neonate with left diaphragmatic hernia. AB - We report a neonate with left congenital diaphragmatic hernia and severe left ventricular dysfunction, in whom the blood flow in the transverse arch and its branches was supported in a retrograde fashion by patent ductus arteriosus. There was only minimal antegrade flow across the aortic valve and hemodynamic physiology resembled critical aortic stenosis, necessitating the immediate use of prostaglandin E1 infusion to maintain the patent ductus arteriosus. PMID- 22676628 TI - Brief cognitive behavioral intervention in groups in a Brazilian assisted reproduction program. AB - The study's objective was to assess the effect of a cognitive behavioral group intervention on the pregnancy rates of patients submitted to in vitro fertilization (IVF) techniques or to intracytoplasmic sperm injection (ICSI). The study was conducted on 188 patients, 93 who participated in a group of psychological intervention before the IVF and ICSI procedures and 95 patients submitted to IVF and ICSI during the same period of time, who did not participate in the intervention (control group). Clinical pregnancy was the outcome measure. Demographic and clinical variables were compared between groups in order to assess the group's homogeneity. Participants in the psychological intervention obtained a pregnancy rate of 39.8%, significantly higher than the 23.2% rate of nonparticipants (chi(2) = 6.03, p = .01, odds ratio of 22 (CI: 1.16-4.13). The data suggest that group psychological intervention before IVF and ICSI in order to control stress seems to increase the rate of success of these procedures. PMID- 22676629 TI - Intervention for homeless, substance abusing mothers: findings from a non randomized pilot. AB - Little empirically-based information is available regarding how best to intervene with substance-abusing homeless mothers. This study pilot-tested a comprehensive intervention with 15 homeless women and their 2- to 6-year-old children, recruited from a local family shelter. All participants were offered integrated intervention with three major components. The first component was housing which included 3 months of rental and utility assistance, and these services were not contingent upon women's abstinence from drugs or alcohol. The second and third components included 6 months of case management services and an evidence-based substance abuse treatment (Community Reinforcement Approach; CRA). Analysis revealed that women showed reductions in substance use (F(2,22) = 3.63; p < .05), homelessness (F(2,24) = 25.31; p < .001), and mental health problems (F(2,20) = 8.5; p < .01). Further, women reported reduced internalizing (F(2,22) = 4.08; p < .05) and externalizing problems (F(2,24) = 7.7; p = .01) among their children. The findings suggest that the intervention is a promising approach to meet the multiple needs of this vulnerable population. These positive outcomes support the need for future research to replicate the findings with a larger sample using a randomized design. PMID- 22676630 TI - Daily life events influence the results of the Dexamethasone Suppression Test in healthy women. AB - Although the Dexamethasone Suppression Test (DST) plays an important role in psychosomatic research, confounding factors limit the sensitivity and specificity of the DST. The aim of this study was to investigate the relationship between the intensity of daily life stressors and DST results in healthy participants after controlling the confounding factors. The subjects of this study consisted of 75 healthy volunteers. The intensity of daily life events was assessed using the Taiwanese version of the Recent Life Change Questionnaire (RLCQ). Neuroticism was assessed using the Maudsley Personality Inventory (MPI). The Dexamethasone Suppression Test (DST) was also performed. The regression model showed that daily life events (RLCQ score) were correlated significantly with cortisol level on day 1 and D% only in women. This finding implies that daily life events should be considered as an independent variable in women in further studies when the DST is applied. PMID- 22676631 TI - Factors associated with illegal motorcycle street racing and help-seeking intention. AB - The study aimed to identify the factors associated with street racing among the illegal motorcycle racers in Malaysia also known as the Mat Rempit, and their help-seeking intention. A total of 2,022 Mat Rempit were surveyed. The findings support the notion that experience-seeking, prestige-seeking, excitement-seeking, self-satisfaction, underestimate risk, and social influence were factors influencing illegal motorcycle street racing. The overall intention to seek help was extremely low. The majority (77.9%) reported that they would solve the problem themselves and 75.5% thought that illegal street racing is not big deal and would go away in time. Participants with neither (OR 0.41; 95% CI 0.27-0.62) or at least one parent who is strict (OR 0.52; 95% 0.37-0.73) were less likely to have high help-seeking intention than those with both parents who are strict. Study indicates a need for family-centered intervention to curb illegal street racing. PMID- 22676632 TI - Mechanism of polymeric nanoparticle-based drug transport across the blood-brain barrier (BBB). AB - In 1995 it was reported for the first time that nanoparticles could be used for the delivery of drugs across the blood-brain barrier (BBB) following intravenous injection. In vitro and in vivo experiments show that the underlying mechanism is receptor-mediated endocytosis followed by transcytosis. No opening of the tight junctions was observed. Due to the overcoating of the nanoparticles with polysorbate 80 or poloxamers 188, apolipoproteins A-I and/or E are adsorbed from the blood on to the particle surface after injection. These apolipoproteins mediate the interaction with LDL or scavenger receptors on the BBB followed by the above brain uptake processes. Likewise, covalent attachment of these apolipoproteins or of transferrin, insulin or antibodies against the respective receptors also enables a similar nanoparticle-mediated drug transport across the BBB. From these results it can be concluded that the nanoparticles act as "Trojan Horses" taking advantage of physiological receptor-mediated transport processes across the BBB. PMID- 22676634 TI - Spatially resolved solid-state 1H NMR for evaluation of gradient-composition polymeric libraries. AB - Polyurethane libraries consisting of films with composition gradients of aliphatic polyisocyanate and hydroxy-terminated polyacrylate resin were characterized using methods of (1)H NMR microimaging (i.e., magnetic resonance imaging, (MRI)) and solid-state NMR. Molecular mobilities and underlying structural information were extracted as a function of the relative content of each of the two components. Routine NMR microimaging using the spin-echo sequence only allows investigations of transverse relaxation of magnetization at echo times >2 ms. A single-exponential decay was found, which is likely due to free, noncross-linked polymer chains. The mobility of these chains decreases with increasing content of the aliphatic polyisocyanate. The concept of a 1D NMR profiler is introduced as a novel modality for library screening, which allows the convenient measurement of static solid-state NMR spectra as a function of spatial location along a library sample that is repositioned in the rf coil between experiments. With this setup the complete transverse relaxation function was measured using Bloch decays and spin echoes. For all positions within the gradient-composition film, relaxation data consisted of at least three components that were attributed to a rigid highly cross-linked resin, an intermediate cross linked but mobile constituent, and the highly mobile free polymer chains (the latter is also detectable by MRI). Analysis of this overall relaxation function measured via Bloch decays and spin echoes revealed only minor changes in the mobilities of the individual fractions. Findings with respect to the most mobile components are consistent with the results obtained by NMR microimaging. The major effect is the significant increase in the rigid-component fraction with the addition of the hydroxy-terminated polyacrylate resin. PMID- 22676633 TI - Psychological distress and mental health service contact of unaccompanied asylum seeking children. AB - BACKGROUND: Evidence is emerging that psychological problems, particularly symptoms of depression and post-traumatic stress disorder, are more prevalent in unaccompanied asylum-seeking children (UASC) than their accompanied peers. However, little is known about help seeking and mental health service (MHS) utilization in this group, and how this relates to their psychological needs. This study aims to describe the level of psychological distress among a group of UASC and the pattern of MHS contact. METHOD: Socio-demographic data on 71 UASC residing in London was obtained and self-report questionnaires were completed regarding trauma events (Harvard Trauma Questionnaire), general psychological distress [Strengths and Difficulties Questionnaire (SDQ)], post-traumatic stress symptoms (Impact of Event Scale), depressive symptoms (Birleson Depression Self Rating Scale for Children) and contact with MHS (Attitudes to Health and Services Questionnaire). RESULTS: UASC were mainly male (n = 48, 67.6%), Black African (n = 39, 54.9%) and their median age was 17 years (interquartile range = 15; 17). They had been living in the UK for a median of 18 months. Eight (11.3%) scored on the SDQ borderline/abnormal range for total symptoms, but this was 21 (29.6%) using the SDQ emotional subscale. Forty-seven (66.2%) were at high risk for post traumatic stress disorder and nine (12.7%) at high risk for depressive disorder. Only 12 (17%) had MHS contact. Predictors of MHS contact were depressive symptoms and duration of time in the UK. CONCLUSIONS: UASC had a high level of emotional symptoms, especially post-traumatic stress symptoms. However, only a small proportion of UASC were in contact with MHS. This suggests a high level of MHS under-utilization, and reasons for this are discussed. PMID- 22676635 TI - Highly resistant bacteria and donor-derived infections: treading in uncharted territory. PMID- 22676639 TI - QLiS--development of a schizophrenia-specific quality-of-life scale. AB - BACKGROUND: The aim of the project was to develop an instrument for the assessment of subjective quality of life specific to schizophrenic persons on the basis of patients' views on their own life and on sound psychometric principles. METHODS: The project applied a six-step multiphase development process with six distinct studies. (1) The elicitation of schizophrenic persons' views on their quality of life was based on open-ended interviews with interviewees from different settings (acute ward inpatients, long-term care patients, community care patients; n = 268). (2) A cross-sectional study with schizophrenic and healthy persons was conducted to quantify the relative importance of the various aspect of quality of life that emerged from the qualitative study (n = 143). (3) We conducted an empirical comparison of response formats with schizophrenic persons (n = 32). (4) A scale construction- and reliability-testing study was performed (n = 203) as well as (5) a test-retest reliability study (n = 49). (6) The final questionnaire (QLiS, quality of life in schizophrenia) was tested in an additional study on convergent and discriminant validity (n = 135). RESULTS: The QLiS comprises 52 items (plus 2 optional items related to work) in 12 subscales: social contacts, appreciation by others, relationship to family, appraisal of pharmacotherapy, appraisal of psychopathological symptoms, cognitive functioning, abilities to manage daily living, appraisal of accommodation/housing, financial situation, leading a 'normal' life, confidence, general life-satisfaction. An item response format with four response categories was preferred by the schizophrenic persons. The mean values of the subscales clustered around the theoretical mean of the subscales and only minimal ceiling effects were found. The reliability (test-retest-reliability and internal consistency) was with one exception > .70 for all subscales. CONCLUSION: Taking the low numbers of items per subscale into account, the QLiS can be regarded as an accurate assessment instrument of subjective quality of life in schizophrenia with good content validity. PMID- 22676640 TI - Medication supply to Residential Aged Care Facilities in Western Australia using a centralized medication chart to replace prescriptions. AB - BACKGROUND: Current model of medication supply to Residential Aged Care Facilities (RACFs) in Australia is dependent on paper-based prescriptions. This study is aimed at assessing the use of a centralized medication chart as a prescription-less model for supplying medications to RACFs. METHODS: Two separate focus groups were conducted with general practitioners (GPs) and pharmacists, and another three with registered nurses (RNs) and carers combined. All focus group participants were working with RACFs. Audio-recorded data were compared with field notes, transcribed and imported into NVivo(r) where it was thematically analyzed. RESULTS: A prescription-less medication chart model was supported and it appeared to potentially improve medication supply to RACF residents. Centralization of medication supply, clarification of medication orders and responding in real-time to therapy changes made by GPs were reasons for supporting the medication chart model. Pharmacists preferred an electronic version of this model. All health professionals cautioned against the need for GPs regularly reviewing the medication chart and proposed a time interval of four to six months for this review to occur. Therapy changes during weekends appeared a potential difficulty for RNs and carers whereas pharmacists cautioned about legible writing and claiming of medications dispensed according to a paper-based model. GPs cautioned on the need to monitor the amount of medications dispensed by the pharmacy. CONCLUSION: The current use of paper prescriptions in nursing homes was identified as burdensome. A prescription-less medication chart model was suggested to potentially improve medication supply to RACF residents. An electronic version of this model could address main potential difficulties raised. PMID- 22676641 TI - Plasma fetuin-A is associated with endothelial dysfunction and subclinical atherosclerosis in subjects with nonalcoholic fatty liver disease. AB - OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD), a hepatic manifestation of metabolic syndrome (MetS) is closely associated with an increased risk of cardiovascular disease. Fetuin-A is associated with MetS and NAFLD. We investigated the relationship of circulating fetuin-A level with markers of endothelial dysfunction and presence of carotid atherosclerosis in subjects with NAFLD. METHODS: The consecutive 115 patients with NAFLD and age-matched 74 healthy subjects were enrolled. Plasma levels of fetuin-A and markers of endothelial dysfunction [asymmetric dimethyl arginine (ADMA) and adiponectin] were measured by ELISA method. Insulin sensitivity was determined by homeostasis model assessment of insulin resistance (HOMA-IR) index. Carotid artery intima media thickness (cIMT) was assessed by high-resolution ultrasonography. RESULTS: Fetuin-A and ADMA were higher and, adiponectin was lower in NAFLD group than the control group (P = 0.004, P < 0.001 and P < 0.001, respectively). In addition, NAFLD group had greater cIMT measurements than the controls (P < 0.001). However, no difference was found for fetuin-A, ADMA, adiponectin and cIMT between two groups when the findings were adjusted according to the glucose, lipids and HOMA IR index. In correlation analysis, fetuin-A was found to be positively correlated with triglyceride (r = 0.23, P = 0.001), HOMA-IR (r = 0.29, P < 0.001), ADMA (r = 0.24, P = 0.001), cIMT (r = 0.3, P = 0.003) and, negatively correlated with HDL-C (r = -0.17, P = 0.02) and adiponectin (r = -0.19, P = 0.01) levels. Multiple linear regression analysis showed that fetuin-A was independently associated with ADMA and cIMT levels. CONCLUSION: This study demonstrated for the first time that circulating fetuin-A in NAFLD is independently associated with endothelial dysfunction and subclinical atherosclerosis. PMID- 22676643 TI - Mulberry leaf polyphenol extract induced apoptosis involving regulation of adenosine monophosphate-activated protein kinase/fatty acid synthase in a p53 negative hepatocellular carcinoma cell. AB - The polyphenols in mulberry leaf possess the ability to inhibit cell proliferation, invasion, and metastasis of tumors. It was reported that the p53 status plays an important role in switching apoptosis and the cell cycle following adenosine monophosphate-activated protein kinase (AMPK) activation. In this study, we aimed to detect the effect of the mulberry leaf polyphenol extract (MLPE) on inducing cell death in p53-negative (Hep3B) and p53-positive (Hep3B with transfected p53) hepatocellular carcinoma cells and also to clarify the role of p53 in MLPE-treated cells. After treatment of the Hep3B cells with MLPE, apoptosis was induced via the AMPK/PI3K/Akt and Bcl-2 family pathways. Transient transfection of p53 into Hep3B cells led to switching autophagy instead of apoptosis by MLPE treatment. We demonstrated that acridine orange staining and protein expressions of LC-3 and beclin-1 were increased in p53-transfected cells. These results implied induction of apoptosis or autophagy in MLPE-treated hepatocellular carcinoma cells can be due to the p53 status. We also found MLPE can not only activate AMPK but also diminish fatty acid synthase, a molecular target for cancer inhibition. At present, our results indicate MLPE can play an active role in mediating the cell death of hepatocellular carcinoma cells and the p53 might play an important role in regulating the death mechanisms. PMID- 22676642 TI - Immunodominant fragments of myelin basic protein initiate T cell-dependent pain. AB - BACKGROUND: The myelin sheath provides electrical insulation of mechanosensory Abeta-afferent fibers. Myelin-degrading matrix metalloproteinases (MMPs) damage the myelin sheath. The resulting electrical instability of Abeta-fibers is believed to activate the nociceptive circuitry in Abeta-fibers and initiate pain from innocuous tactile stimulation (mechanical allodynia). The precise molecular mechanisms, responsible for the development of this neuropathic pain state after nerve injury (for example, chronic constriction injury, CCI), are not well understood. METHODS AND RESULTS: Using mass spectrometry of the whole sciatic nerve proteome followed by bioinformatics analyses, we determined that the pathways, which are classified as the Infectious Disease and T-helper cell signaling, are readily activated in the nerves post-CCI. Inhibition of MMP-9/MMP 2 suppressed CCI-induced mechanical allodynia and concomitant TNF-alpha and IL 17A expression in nerves. MMP-9 proteolysis of myelin basic protein (MBP) generated the MBP84-104 and MBP68-86 digest peptides, which are prominent immunogenic epitopes. In agreement, the endogenous MBP69-86 epitope co-localized with MHCII and MMP-9 in Schwann cells and along the nodes of Ranvier. Administration of either the MBP84-104 or MBP68-86 peptides into the naive nerve rapidly produced robust mechanical allodynia with a concomitant increase in T cells and MHCII-reactive cell populations at the injection site. As shown by the genome-wide expression profiling, a single intraneural MBP84-104 injection stimulated the inflammatory, immune cell trafficking, and antigen presentation pathways in the injected naive nerves and the associated spinal cords. Both MBP84 104-induced mechanical allodynia and characteristic pathway activation were remarkably less prominent in the T cell-deficient athymic nude rats. CONCLUSIONS: These data implicate MBP as a novel mediator of pain. Furthermore, the action of MMPs expressed within 1 day post-injury is critical to the generation of tactile allodynia, neuroinflammation, and the immunodominant MBP digest peptides in nerve. These MBP peptides initiate mechanical allodynia in both a T cell dependent and -independent manner. In the course of Wallerian degeneration, the repeated exposure of the cryptic MBP epitopes, which are normally sheltered from immunosurveillance, may induce the MBP-specific T cell clones and a self sustaining immune reaction, which may together contribute to the transition of acute pain into a chronic neuropathic pain state. PMID- 22676644 TI - The mind's scalpel in surgical education: a randomised controlled trial of mental imagery. AB - OBJECTIVE: To evaluate the role of mental imagery (MI) in resident training for a complex surgical procedure. DESIGN: Randomised controlled trial. SETTING: Eight centres across Canada and the USA. POPULATION: Junior gynaecology residents who had performed fewer than five vaginal hysterectomies (VH). METHODS: After performing a pretest VH, junior gynaecology residents were randomised to standard MI versus textbook reading (No MI) and then performed a test VH. Surgeons blinded to group evaluated resident performance on the pretest and test VH via global rating scales (GRS), procedure-specific scales and intraoperative parameters. Residents evaluated their own performance. MAIN OUTCOME MEASURE: Change in surgeon GRS score from pretest to test VH. The study was powered to detect a 20% difference in score change. RESULTS: Fifty residents completed the trial (24 MI, 26 No MI). There was no difference in GRS score change via blinded assessment from pretest to test evaluation between groups (mean change 13% [SD 17] versus 7% [SD 14], P = 0.192). There was no difference in procedure-specific score change. There was a significant difference in self-scored GRS score change between groups (mean change 19% [SD 12] versus 9% [SD 11], P = 0.005). Residents also felt more confident performing a VH (mean change 19% [SD 16] MI versus 11% [SD 10] No MI, P = 0.033). CONCLUSIONS: No difference was observed in the surgical performance of residents after MI. Improved resident self-confidence may be attributable to MI or the effect of unblinding on trial participants. PMID- 22676645 TI - Electromagnetic fields and health: DNA-based dosimetry. AB - We propose a biologically based measure of EMF radiation to replace the energy based "specific absorption rate" (SAR). A wide range of EMF frequencies has been linked to an increased risk of cancer. The SAR value used to measure the EMF dose and set the safety standard in the radiofrequency (RF) range fails as a standard for predicting cancer risk in the ELF power frequency range. Because cancers are believed to arise from mutations in DNA, changes in DNA induced by interaction with EMF could be a better measure of the biologically effective dose in both frequency ranges. The changes can be measured by transcriptional alterations and/or translational changes in specific proteins. Because ionizing radiation also causes DNA damage, a biologically based standard related to stimulation of DNA could apply over a much wider range of the electromagnetic spectrum. A safety standard for exposure to a wide range of non ionizing frequencies can be based on the documented changes in DNA biochemistry that arise from interactions with EMF. PMID- 22676646 TI - Macrophage migration inhibitory factor is elevated in obese adolescents. AB - OBJECTIVES: The prevalence of obesity in childhood and adolescence is continuing rising. Macrophage migration inhibitory factor (MIF) participates in inflammatory and immune responses as a pro-inflammatory cytokine. The present study aimed to investigate MIF in overweight adolescents. METHODS: Seventy-nine male adolescents were enrolled. Thirty-eight were overweight according to the 90th%ile of the age specific waist circumference. Various parameters were recorded at one visit, including body mass index. MIF was determined using multiplex immune-assay technology. RESULTS: Overweight adolescents had increased systolic blood pressure and CRP levels. Furthermore, increased circulating MIF concentrations were observed (Median: 964.6 pg/ml, Interquartile range: 590.3-2019.4 versus Median: 562.7 pg/ml, Interquartile range: 430.6-813.7, p = 0.003). Increased MIF concentrations were associated with increased markers of inflammation and obesity. CONCLUSIONS: We demonstrated elevated MIF levels in obese adolescents. Taken together with other markers, this indicates the presence of low-grade inflammation in these young subjects, possibly representing a link between obesity and related co-morbidities. PMID- 22676647 TI - Increase of lower esophageal sphincter pressure after osteopathic intervention on the diaphragm in patients with gastroesophageal reflux. AB - The treatment of gastroesophageal reflux disease may be clinical or surgical. The clinical consists basically of the use of drugs; however, there are new techniques to complement this treatment, osteopathic intervention in the diaphragmatic muscle is one these. The objective of the study is to compare pressure values in the examination of esophageal manometry of the lower esophageal sphincter (LES) before and immediately after osteopathic intervention in the diaphragm muscle. Thirty-eight patients with gastroesophageal reflux disease - 16 submitted to sham technique and 22 submitted osteopathic technique - were randomly selected. The average respiratory pressure (ARP) and the maximum expiratory pressure (MEP) of the LES were measured by manometry before and after osteopathic technique at the point of highest pressure. Statistical analysis was performed using the Student's t-test and Mann-Whitney, and magnitude of the technique proposed was measured using the Cohen's index. Statistically significant difference in the osteopathic technique was found in three out of four in relation to the group of patients who performed the sham technique for the following measures of LES pressure: ARP with P= 0.027. The MEP had no statistical difference (P= 0.146). The values of Cohen d for the same measures were: ARP with d= 0.80 and MEP d= 0.52. Osteopathic manipulative technique produces a positive increment in the LES region soon after its performance. PMID- 22676649 TI - Vibrational spectroscopy and theory of the protonated benzene dimer and trimer. AB - Protonated benzene cluster ions, H(C(6)H(6))(2)(+) and H(C(6)H(6))(3)(+), are produced in a pulsed electrical discharge source coupled to a supersonic expansion. Mass-selected complexes are investigated with infrared photodissociation spectroscopy in the 1000-3200 cm(-1) region using the method of argon tagging. The IR spectra of H(C(6)H(6))(2)(+)-Ar and H(C(6)H(6))(3)(+)-Ar contain broad bands in the high frequency region resulting from CH-pi hydrogen bonds. Sharp peaks are observed in the fingerprint region arising from the ring modes of both the C(6)H(7)(+) and C(6)H(6) moieties. M06-2X calculations have been performed to investigate the structures and vibrational spectra of energetically low-lying configurations of these complexes. H(C(6)H(6))(2)(+) is predicted to have three nearly isoenergetic conformers: the parallel displaced (PD), T-shaped (TS), and canted (C) structures [Jaeger, H. M.; Schaefer, H. F.; Hohenstein, E. G.; Sherrill, C. D. Comput. Theor. Chem. 2011, 973, 47-52]. A comparison of the experimental dimer spectrum with those predicted for the three isomers suggests an average structure between the TS and PD conformers, which is consistent with the low energy barrier predicted to separate these two structures. No evidence is found for the C dimer even though it lies only 1.2 kcal/mol above the PD dimer. Although the trimer is also computed to have many low lying isomers, the IR spectrum limits the possible species present. PMID- 22676648 TI - A stitch in time: a cross-sectional survey looking at long lasting insecticide treated bed net ownership, utilization and attrition in SNNPR, Ethiopia. AB - BACKGROUND: Since 2002/03, an estimated 4.7 million nets have been distributed in the Southern Nations, Nationalities and Peoples Region (SNNPR) among an at risk population of approximately 10 million people. Evidence from the region suggests that large-scale net ownership rapidly increased over a relatively short period of time. However, little is known about how coverage is being maintained given that the last mass distribution was in 2006/2007. This study sought to determine the status of current net ownership, utilization and rate of long lasting insecticide-treated nets (LLIN) loss in the previous three years in the context of planning for future net distribution to try to achieve sustainable universal coverage. METHODS: A total of 750 household respondents were interviewed across malarious, rural kebeles of SNNPR. Households were randomly selected following a two-stage cluster sampling design where kebeles were defined as clusters. Kebeles were chosen using proportional population sampling (PPS), and 25 households within 30 kebeles randomly chosen. RESULTS: Approximately 67.5% (95%CI: 64.1 70.8) of households currently owned at least one net. An estimated 31.0% (95%CI 27.9-34.4) of all nets owned in the previous three years had been discarded by owners, the majority of whom considered the nets too torn, old or dirty (79.9%: 95%CI 75.8-84.0). Households reported that one-third of nets (33.7%) were less than one year old when they were discarded. The majority (58.8%) of currently owned nets had 'good' structural integrity according to a proportionate Hole Index. Nearly two-thirds of households (60.6%) reported using their nets the previous night. The overriding reason for not using nets was that they were too torn (45.7%, 95% CI 39.1-50.7). Yet, few households are making repairs to their nets (3.7%, 95% CI: 2.4-5.1). CONCLUSIONS: Results suggest that the life span of nets may be shorter than previously thought, with little maintenance by their owners. With the global move towards malaria elimination it makes sense to aim for sustained high coverage of LLINs. However, in the current economic climate, it also makes sense to hark back to simple tools and messages on the importance of careful net maintenance, which could increase their lifespans. PMID- 22676650 TI - The impact of on-road motion on BMS touch screen device operation. AB - This study investigates the effect of vehicle motion on performance, usability and workload for a touch screen in-vehicle Battle Management System (BMS). Participants performed a series of battle management tasks while a vehicle was driven over sealed (characteristic of 'normal' vehicle motion) and unsealed (characteristic of 'high' vehicle motion) roads. The results indicate that unsealed road conditions impair the performance of information input tasks (tasks that require the user to enter information, e.g. text entry) but not information extraction tasks (tasks that require the user to retrieve information from the system, e.g. reading coordinates). Participants rated workload as higher and the system as less usable on the unsealed road. In closing, the implications for in vehicle touch screen design and use in both military and civilian driving contexts are discussed. Practitioner Summary: The effect of motion on interacting with in-vehicle touch screen devices remains largely unexplored. This study examines the effect of different levels of vehicle motion on the use of a BMS. Using the system under off-road conditions had a detrimental impact on workload, performance and usability. PMID- 22676652 TI - RNA: methods and protocols - a new series. AB - This month, Silence launches a new series on methods and protocols to study silencing pathways and analyze nucleic acids and proteins. PMID- 22676651 TI - A cross-sectional single-centre study on the spectrum of Pompe disease, German patients: molecular analysis of the GAA gene, manifestation and genotype phenotype correlations. AB - BACKGROUND: Pompe disease (Glycogen storage disease type II, GSD II, acid alpha glucosidase deficiency, acid maltase deficiency, OMIM # 232300) is an autosomal recessive lysosomal storage disorder due to a deficiency of acid alpha glucosidase (GAA, acid maltase, EC 3.2.1.20, Swiss-Prot P10253). Clinical manifestations are dominated by progressive weakness of skeletal muscle throughout the clinical spectrum. In addition, the classic infantile form is characterised by hypertrophic cardiomyopathy. METHODS: In a cross-sectional single-centre study we clinically assessed 3 patients with classic infantile Pompe disease and 39 patients with non-classic presentations, measured their acid alpha-glucosidase activities and analysed their GAA genes. RESULTS: Classic infantile patients had nearly absent residual enzyme activities and a typical clinical course with hypertrophic cardiomyopathy until the beginning of therapy. The disease manifestations in non-classic patients were heterogeneous. There was a broad variability in the decline of locomotive and respiratory function. The age of onset ranged from birth to late adulthood and correlated with enzyme activities. Molecular analysis revealed as many as 33 different mutations, 14 of which are novel. All classic infantile patients had two severe mutations. The most common mutation in the non-classic group was c.-32-13T>G. It was associated with a milder course in this subgroup. CONCLUSIONS: Disease manifestation strongly correlates with the nature of the GAA mutations, while the variable progression in non-classic Pompe disease is likely to be explained by yet unknown modifying factors. This study provides the first comprehensive dataset on the clinical course and the mutational spectrum of Pompe disease in Germany. PMID- 22676653 TI - Mutagenesis of RpoE-like sigma factor genes in Bdellovibrio reveals differential control of groEL and two groES genes. AB - BACKGROUND: Bdellovibrio bacteriovorus HD100 must regulate genes in response to a variety of environmental conditions as it enters, preys upon and leaves other bacteria, or grows axenically without prey. In addition to "housekeeping" sigma factors, its genome encodes several alternate sigma factors, including 2 Group IV RpoE-like proteins, which may be involved in the complex regulation of its predatory lifestyle. RESULTS: We find that one sigma factor gene, bd3314, cannot be deleted from Bdellovibrio in either predatory or prey-independent growth states, and is therefore possibly essential, likely being an alternate sigma 70. Deletion of one of two Group IV-like sigma factor genes, bd0881, affects flagellar gene regulation and results in less efficient predation, although not due to motility changes; deletion of the second, bd0743, showed that it normally represses chaperone gene expression and intriguingly we find an alternative groES gene is expressed at timepoints in the predatory cycle where intensive protein synthesis at Bdellovibrio septation, prior to prey lysis, will be occurring. CONCLUSIONS: We have taken the first step in understanding how alternate sigma factors regulate different processes in the predatory lifecycle of Bdellovibrio and discovered that alternate chaperones regulated by one of them are expressed at different stages of the lifecycle. PMID- 22676697 TI - Optimizing the dose of dabigatran etexilate. PMID- 22676698 TI - Aggressive coronary artery vasculopathy after combined heart-lung transplantation. AB - Combined heart-lung transplantation remains as a treatment option for patients with cardiopulmonary failure. There is speculation that lung grafts protect the heart from developing graft vasculopathy after combined heart-lung transplantation. This protective mechanism is more likely, at best, a delay in the onset of coronary artery vasculopathy. We present our experiences in two cases of an aggressive form of cardiac allograft vasculopathy after combined heart-lung transplantation that resulted in the death of both patients. PMID- 22676699 TI - Clinical evaluation of a computerized self-administered hearing test. AB - OBJECTIVE: To establish the reliability and validity of a computerized self administered hearing test. DESIGN: Cross-sectional within a comparative study of subjects. STUDY SAMPLE: Subjects were 100 Chinese adults who attended the audiology clinic in a hospital for a hearing test. RESULTS: There was no significant difference in the thresholds of unmasked air-conduction hearing obtained with the computerized self-administered hearing test via a smartphone and those obtained with standard pure-tone audiometry. High test-retest reliability was observed with the self-administered hearing test (intraclass correlation coefficient = 0.95), and was comparable with that observed in standard pure-tone audiometry (intraclass correlation coefficient = 0.97). The thresholds of the self-administered hearing test measured in a sound-proof booth were not significantly different from those measured in a quiet office room. CONCLUSIONS: The results suggest that the computerized self-administered hearing test is a reliable and valid measure of unmasked air-conduction hearing thresholds. PMID- 22676700 TI - Accuracy of distortion-product otoacoustic emissions-based ototoxicity monitoring using various primary frequency step-sizes. AB - OBJECTIVE: A cisplatin ototoxicity monitoring protocol was recently proposed using distortion-product otoacoustic emissions (DPOAEs) measured in 1/48th octave steps over the highest obtainable quarter octave ( Dille et al, 2010 ). This protocol can take up to 40 minutes to complete in both ears among seriously ill patients in a potentially noisy test environment. The goal of the current study was to contrast the diagnostic accuracy of ototoxicity monitoring protocols based on changes in DPOAE levels at wider, more rapidly tested, primary frequency step sizes. DESIGN: Measure DPOAE levels in 1/48th octave steps over the highest half octave of obtainable DPOAEs prior to treatment and at each ototoxicity monitoring session during the course of treatment with cisplatin. STUDY SAMPLE: Nineteen cancer patients being treated with cisplatin at the Portland Veterans Affairs Medical Center were observed over 56 monitoring appointments. Hearing thresholds in the sensitive region for ototoxicity (SRO) were measured concurrently with DPOAE levels. RESULTS: DPOAE levels measured in 1/24th octave steps provided comparable accuracy, and half the testing time, to the 1/48th octave step protocol previously described. CONCLUSIONS: DPOAE level shifts measured in 1/24th octave steps may provide a basis for rapid ototoxicity monitoring among adult cancer patients treated with cisplatin. PMID- 22676701 TI - Relevance of maintenance triple-drug immunosuppression to bridle the amplification of rat cytomegalovirus infection after experimental lung transplantation. AB - Immunosuppressive therapy required to treat rejection after lung transplantation (LTx) contributes significantly to the pathogenesis of cytomegalovirus (CMV) infection and disease. In a weak allogeneic left LTx model in the rat (Fisher 344 [F344] to Wistar Kyoto [WKY] rats) we analyzed the influence of acute CMV infection on postoperative day (POD) 3, with application of standard triple-drug immunosuppression (TD-IS) (cyclosporin A, azathioprine, prednisolone) on late outcome after LTx. Native right lungs and syngeneic grafts (WKY to WKY) served as controls. Rats were sacrificed on POD 15, 30, 60, and 100. TD-IS completely prevented acute and chronic rejection in non-infected rats. Allografts of CMV infected rats treated with TD-IS showed only mild perivascular infiltrations in 6/10 rats (POD 15 and 30), which persisted up to POD 100 in 4/10 rats. In the long-term course, mild isolated interstitial and alveolar changes were found in 40% of these animals. In conclusion, rat CMV infection partially neutralized the immunosuppressive effect of TD-IS. However, an amplification of CMV infection under TD-IS can be controlled and does not result in fatal outcome. PMID- 22676702 TI - Heavy doping and band engineering by potassium to improve the thermoelectric figure of merit in p-type PbTe, PbSe, and PbTe(1-y)Se(y). AB - We present detailed studies of potassium doping in PbTe(1-y)Se(y) (y = 0, 0.15, 0.25, 0.75, 0.85, 0.95, and 1). It was found that Se increases the doping concentration of K in PbTe as a result of the balance of electronegativity and also lowers the lattice thermal conductivity because of the increased number of point defects. Tuning the composition and carrier concentration to increase the density of states around the Fermi level results in higher Seebeck coefficients for the two valence bands of PbTe(1-y)Se(y). Peak thermoelectric figure of merit (ZT) values of ~1.6 and ~1.7 were obtained for Te-rich K(0.02)Pb(0.98)Te(0.75)Se(0.25) at 773 K and Se-rich K(0.02)Pb(0.98)Te(0.15)Se(0.85) at 873 K, respectively. However, the average ZT was higher in Te-rich compositions than in Se-rich compositions, with the best found in K(0.02)Pb(0.98)Te(0.75)Se(0.25). Such a result is due to the improved electron transport afforded by heavy K doping with the assistance of Se. PMID- 22676703 TI - Fungal melanonychia and Exophiala dermatitidis. PMID- 22676707 TI - Nutritional and functional evaluation of wheat flour cookies supplemented with gram flour. AB - Protein-enriched cookies were prepared by supplementing gram flour into wheat flour at levels of 0%, 10%, 20%, 30%, 40% and 50% and analysed for physicochemical properties. The protein quality of the cookies was assessed by feeding gram flour-supplemented cookies to albino rats for 10 days. The supplementation resulted in a significant increase in protein, fat, crude fibre and ash contents of the cookies. The thickness and spread factor of cookies differ significantly while non-significant effect was observed in the width of the cookies. The protein efficiency ratio, net protein utilization, biological value and true digestibility differed significantly among diets containing cookies with gram flour fed to rats. Cookies with 30% substitution of straight grade flour and gram flour produced acceptable cookies as compared to control. The cookies containing 40-50% gram flour were best regarded as protein bioavailability for rats. PMID- 22676708 TI - Temporal strategy and performance during a fatiguing short-cycle repetitive task. AB - This study investigated temporal changes in movement strategy and performance during fatiguing short-cycle work. Eighteen participants performed six 7-min work blocks with repetitive reaching movements at 0.5 Hz, each followed by a 5.5-min rest break for a total duration of 1 h. Electromyography (EMG) was collected continuously from the upper trapezius muscle, the temporal movement strategy and timing errors were obtained on a cycle-to-cycle basis, and perceived fatigue was rated before and after each work block. Clear signs of fatigue according to subjective ratings and EMG manifestations developed within each work block, as well as during the entire hour. For most participants, timing errors gradually increased, as did the waiting time at the near target. Changes in temporal movement strategy were negatively correlated with changes in the level and variability of EMG, suggesting that an adaptive temporal strategy offset the development of unstable motor solutions in this fatiguing, short-cycle work. PRACTITIONER SUMMARY: Sustained performance of operators is essential to maintain competitiveness. In this study of repetitive work, participants gradually changed their temporal movement strategy, for possibly alleviating the effects of fatigue. This suggests that in order to effectively counteract fatigue and sustain performance, industrial production should allow extensive spatial and temporal flexibility. PMID- 22676709 TI - BowStrap v1.0: Assigning statistical significance to expressed genes using short read transcriptome data. AB - BACKGROUND: Background: Deep RNA sequencing, the application of Next Generation sequencing technology to generate a comprehensive profile of the message RNA present in a set of biological samples, provides unprecedented resolution into the molecular foundations of biological processes. By aligning short read RNA sequence data to a set of gene models, expression patterns for all of the genes and gene variants in a biological sample can be calculated. However, accurate determination of gene model expression from deep RNA sequencing is hindered by the presence of ambiguously aligning short read sequences. FINDINGS: BowStrap, a program for implementing the sequence alignment tool 'Bowtie' in a bootstrap style approach, accommodates multiply-aligning short read sequences and reports gene model expression as an averaged aligned reads per Kb of gene model sequence per million aligned deep RNA sequence reads with a confidence interval, suitable for calculating statistical significance of presence/absence of detected gene model expression. BowStrap v1.0 was validated against a simulated metatranscriptome. Results were compared with two alternate 'Bowtie'-based calculations of gene model expression. BowStrap is better at accurately identifying expressed gene models in a dataset and provides a more accurate estimate of gene model expression level than methods that do not incorporate a boot-strap style approach. CONCLUSIONS: BowStrap v1.0 is superior in ability to detect significant gene model expression and calculate accurate determination of gene model expression levels compared to other alignment-based methods of determining patterns of gene expression. BowStrap v1.0 also can utilize multiple processors as has decreased run time compared to the previous version, BowStrap 0.5. We anticipate that BowStrap will be a highly useful addition to the available set of Next Generation RNA sequence analysis tools. PMID- 22676710 TI - Developing a new self-reported scale of oral health outcomes for 5-year-old children (SOHO-5). AB - BACKGROUND: Information on the impact of oral health on quality of life of children younger than 8 years is mostly based on parental reports, as methodological and conceptual challenges have hindered the development of relevant validated self-reported measures. This study aimed to develop and assess the reliability and validity of a new self-reported oral health related quality of life measure, the Scale of Oral Health Outcomes for 5-year-old children (SOHO 5), in the UK. METHODS: A cross-sectional study of two phases. First, consultation focus groups (CFGs) with parents of 5-year-olds and review by experts informed the development of the SOHO-5 questionnaire. The second phase assessed its reliability and validity on a sample of grade 1 (5-year-old) primary schoolchildren in the Greater Glasgow and Clyde area, Scotland. Data were linked to available clinical oral health information and analysis involved associations of SOHO-5 with subjective and clinical outcomes. RESULTS: CFGs identified eating, drinking, appearance, sleeping, smiling, and socialising as the key oral impacts at this age. 332 children participated in the main study and for 296 (55% girls, mean d3mft: 1.3) clinical data were available. Overall, 49.0% reported at least one oral impact on their daily life. The most prevalent impacts were difficulty eating (28.7%), difficulty sleeping (18.5%), avoiding smiling due to toothache (14.9%) and avoiding smiling due to appearance (12.5%). The questionnaire was quick to administer, with very good comprehension levels. Cronbach's alpha was 0.74 and item-total correlation coefficients ranged between 0.30 and 0.60, demonstrating the internal consistency of the new measure. For validity, SOHO-5 scores were significantly associated with different subjective oral health outcomes (current toothache, toothache lifetime experience, satisfaction with teeth, presence of oral cavities) and an aggregate measure of clinical and subjective oral health outcomes. The new measure also discriminated between different clinical groups in relation to active caries, pulp involvement, and dental sepsis. CONCLUSIONS: This is the first study to develop and validate a self-reported oral health related quality of life measure for 5-year-old children. Initial reliability and validity findings were very satisfactory. SOHO 5 can be a useful tool in clinical studies and public health programs. PMID- 22676712 TI - Induction of atrial fibrillation with adenosine during a transesophageal electrophysiology study to risk stratify a patient with asymptomatic ventricular preexcitation. AB - An asymptomatic adolescent male athlete was incidentally found to have ventricular preexcitation on electrocardiogram during a sports preparticipation physical. A transesophageal electrophysiology study (TEEPS) was performed after an exercise stress test failed to delineate the patient's risk of sudden cardiac death. The TEEPS was favored in this case over a transvenous electrophysiology study due to reduced invasiveness. The goal of the TEEPS was to place the patient into atrial fibrillation (AFib) and evaluate the shortest preexcited RR interval during AFib, thereby assessing the risk of his accessory pathway. Conventional pacing modalities were unable to induce AFib. During atrial burst pacing, adenosine was then administered, which successfully induced AFib. This case highlights adenosine's potential to induce atrial fibrillation during transesophageal electrophysiology studies when atrial pacing alone was unable to do so. PMID- 22676711 TI - Pharmacogenomics of warfarin in populations of African descent. AB - Warfarin is the most commonly prescribed oral anticoagulant worldwide despite its narrow therapeutic index and the notorious inter- and intra-individual variability in dose required for the target clinical effect. Pharmacogenetic polymorphisms are major determinants of warfarin pharmacokinetic and dynamics and included in several warfarin dosing algorithms. This review focuses on warfarin pharmacogenomics in sub-Saharan peoples, African Americans and admixed Brazilians. These 'Black' populations differ in several aspects, notably their extent of recent admixture with Europeans, a factor which impacts on the frequency distribution of pharmacogenomic polymorphisms relevant to warfarin dose requirement for the target clinical effect. Whereas a small number of polymorphisms in VKORC1 (3673G > A, rs9923231), CYP2C9 (alleles *2 and *3, rs1799853 and rs1057910, respectively) and arguably CYP4F2 (rs2108622), may capture most of the pharmacogenomic influence on warfarin dose variance in White populations, additional polymorphisms in these, and in other, genes (e.g. CALU rs339097) increase the predictive power of pharmacogenetic warfarin dosing algorithms in the Black populations examined. A personalized strategy for initiation of warfarin therapy, allowing for improved safety and cost effectiveness for populations of African descent must take into account their pharmacogenomic diversity, as well as socio-economical, cultural and medical factors. Accounting for this heterogeneity in algorithms that are 'friendly' enough to be adopted by warfarin prescribers worldwide requires gathering information from trials at different population levels, but demands also a critical appraisal of racial/ethnic labels that are commonly used in the clinical pharmacology literature but do not accurately reflect genetic ancestry and population diversity. PMID- 22676713 TI - Is the way to a man's heart through his stomach? Enteropericardial fistula: case series and literature review. AB - Fistula formation between the pericardium and the gastrointestinal tract is rare. Enteropericardial fistulae may present dramatically, many have prodromal symptoms even though they are not symptoms usually associated with esophageal disease. Prompt diagnosis and expedient surgery can result in survival. We describe three cases of enteropericardial fistulae diagnosed during emergency surgery for sepsis or hemorrhage. All had previous surgery though the details were not available to the operating surgeons because of the time that had passed since their original operation. All three patients survived, albeit with prolonged hospital stay and repeated surgery. A review of the English language literature revealed 95 cases (Table 1). Fifty-eight had a history of previous surgery, particularly fundoplication or esophagectomy. Ten had advanced malignancy and were treated conservatively. All eight patients with fistulae, which were iatrogenic or due to foreign bodies, survived without aggressive surgery. For more extensive pathology, a successful outcome was achieved in 32 of the 36 cases when the upper gastrointestinal (GI) tract was defunctioned because of the presence of major sepsis or because the healthy vascularized tissue was transposed into the area at risk for further fistula formation. Where less aggressive surgery was performed only 12 of 27 patients survived (P < 0.0001). Esophageal surgeons need to be aware of the late complications and associated atypical symptoms of historical procedures which are no longer in common usage. Where an enteropericardial fistula is present, defunctioning of the upper GI tract or repair with transposition of vascularized tissue gives a better chance of a successful outcome. [Table: see text]. PMID- 22676714 TI - The modulating impact of illumination and background radiation on 8 Hz-induced infrasound effect on physicochemical properties of physiolagical solution. AB - At present, when the level of background ionizing radiation is increasing in a number of world locations, the problem of the study of biological effect of high background radiation becomes one of the extremely important global problems in modern life sciences. The modern research in biophysics proved that water is a most essential target, through which the biological effects of ionizing and non ionizing radiations are realized. Therefore, there is no doubt about the strong dependency of non-ionizing radiation-induced effect on the level of background radiation. Findings have shown that illumination and background radiation have a strong modulation effect on infrasound-induced impacts on water physicochemical properties, which could also have appropriate effect on living organisms. PMID- 22676715 TI - Growth and tolerance of infants fed formula supplemented with polydextrose (PDX) and/or galactooligosaccharides (GOS): double-blind, randomized, controlled trial. AB - BACKGROUND: To ensure the suitability of an infant formula as the sole source of nutrition or provide benefits similar to outcomes in breastfed infants, advancements in formula composition are warranted as more research detailing the nutrient composition of human milk becomes available. This study was designed to evaluate growth and tolerance in healthy infants who received one of two investigational cow's milk-based formulas with adjustments in carbohydrate, fat, and calcium content and supplemented with a prebiotic blend of polydextrose (PDX) and galactooligosaccharides (GOS) or GOS alone. METHODS: In this multi-center, double-blind, parallel-designed, gender-stratified prospective study 419 infants were randomized and consumed either a marketed routine cow's milk-based infant formula (Control; Enfamil(r) LIPIL(r), Mead Johnson Nutrition, Evansville, IN) (n = 142) or one of two investigational formulas from 14 to 120 days of age. Investigational formulas were supplemented with 4 g/L (1:1 ratio) of a prebiotic blend of PDX and GOS (PDX/GOS; n = 139) or 4 g/L of GOS alone (GOS; n = 138). Anthropometric measurements were taken at 14, 30, 60, 90, and 120 days of age. Daily recall of formula intake, tolerance, and stool characteristics was collected during study weeks 1 and 2 and 24-h recall was collected at 60, 90, and 120 days of age. Medically-confirmed adverse events were recorded throughout the study. RESULTS: There were no group differences in growth rate from 14 to 120 days of age. Discontinuation rates were not significantly different among study groups. No differences in formula intake or infant fussiness or gassiness were observed. During study weeks 1 and 2 and at 60 days of age stool consistency ratings were higher (i.e. softer stools) for infants in the PDX/GOS and GOS groups versus Control and remained higher at 120 days for the PDX/GOS group (all P < 0.05). The overall incidence of medically-confirmed adverse events was similar among groups. CONCLUSIONS: Investigational routine infant formulas supplemented with 4 g/L of either a prebiotic blend of PDX and GOS or GOS alone were well-tolerated and supported normal growth. Compared to infants who received the unsupplemented control formula, infants who received prebiotic supplementation experienced a softer stooling pattern similar to that reported in breastfed infants. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00712608. PMID- 22676716 TI - Phosphoglucomutase is absent in Trypanosoma brucei and redundantly substituted by phosphomannomutase and phospho-N-acetylglucosamine mutase. AB - The enzymes phosphomannomutase (PMM), phospho-N-acetylglucosamine mutase (PAGM) and phosphoglucomutase (PGM) reversibly catalyse the transfer of phosphate between the C6 and C1 hydroxyl groups of mannose, N-acetylglucosamine and glucose respectively. Although genes for a candidate PMM and a PAGM enzymes have been found in the Trypanosoma brucei genome, there is, surprisingly, no candidate gene for PGM. The TbPMM and TbPAGM genes were cloned and expressed in Escherichia coli and the TbPMM enzyme was crystallized and its structure solved at 1.85 A resolution. Antibodies to the recombinant proteins localized endogenous TbPMM to glycosomes in the bloodstream form of the parasite, while TbPAGM localized to both the cytosol and glycosomes. Both recombinant enzymes were able to interconvert glucose-phosphates, as well as acting on their own definitive substrates. Analysis of sugar nucleotide levels in parasites with TbPMM or TbPAGM knocked down by RNA interference (RNAi) suggests that, in vivo, PGM activity is catalysed by both enzymes. This is the first example in any organism of PGM activity being completely replaced in this way and it explains why, uniquely, T. brucei has been able to lose its PGM gene. The RNAi data for TbPMM also showed that this is an essential gene for parasite growth. PMID- 22676717 TI - Administration of COG1410 reduces axonal amyloid precursor protein immunoreactivity and microglial activation after controlled cortical impact in mice. AB - Traumatic axonal injury (TAI) accounts for at least 35% of the morbidity and mortality in traumatic brain injury (TBI) patients without space-occupying lesions. It is also believed to be a key determinant of adverse outcomes such as cognitive dysfunction across the spectrum of TBI severity. Previous studies have shown that COG1410, a synthetic peptide derived from the apolipoprotein E (apoE) receptor binding region, has anti-inflammatory effects after experimental TBI, with improvements in cognitive recovery. However, the effects of COG1410 on axonal injury following TBI are not known. The current study evaluated the effects of 1 mg/kg daily COG1410 versus saline administered intravenously starting 30 min after controlled cortical impact (CCI) injury on pericontusional TAI in young, wild-type C57BL6/J male mice. We found that COG1410 did not affect the number of amyloid precursor protein (APP)-immunoreactive axonal varicosities in the pericontusional corpus callosum and external capsule at 24 h, but reduced APP-immunoreactive varicosities by 31% at 3 days (p=0.0023), and 36% at 7 days (p=0.0009). COG1410 significantly reduced the number of Iba1-positive cells with activated microglial morphology at all three time points by 21-30%. There was no effect of COG1410 on pericontusional white matter volume or silver staining at any time point. This indicates a possible effect of COG1410 on delayed but not immediate TAI. Future studies are needed to investigate the underlying mechanisms, therapeutic time window, and physiological implications of this effect. PMID- 22676720 TI - Non-tuberculous mycobacterial infection among lung transplant recipients: a 15 year cohort study. AB - BACKGROUND: The incidence of infection with non-tuberculous mycobacteria (NTM) after lung transplant is insufficiently defined. Data on the impact of NTM infection on lung transplant survival are conflicting. METHODS: To quantify the incidence and outcomes of colonization and disease with NTM in patients after lung transplantation, the medical records, chest imaging, and microbiology data of 237 consecutive lung transplant recipients between 1990 and 2005 were reviewed. American Thoracic Society (ATS)/Infectious Diseases Society of America and Centers for Disease Control criteria were used to define pulmonary NTM disease and NTM surgical-site infections (SSI), respectively. Incidence rates for NTM colonization and disease were calculated. Comparisons of median survival were done using the log-rank test. RESULTS: NTM were isolated from 53 of 237 patients (22.4%) after lung transplantation over a median of 25.2 months of follow-up. The incidence rate of NTM isolation was 9.0/100 person-years (95% confidence interval [CI), 6.8-11.8), and the incidence rate of NTM disease was 1.1/100 person-years (95% CI 0.49-2.2). The most common NTM isolated was Mycobacterium avium complex (69.8%), followed by Mycobacterium abscessus (9.4%), and Mycobacterium gordonae (7.5%). Among these 53 patients, only 2 patients met ATS criteria for pulmonary disease and received treatment for M. avium. One patient had recurrent colonization after treatment, the other one was cured. Four of the 53 patients developed SSI, 3 caused by M. abscessus and 1 caused by Mycobacterium chelonae. Three of these patients had persistent infection requiring chronic suppressive therapy and one died from progressive disseminated disease. A total of 47 (89%) patients who met microbiologic but not radiographic criteria for pulmonary infection were not treated and were found to have only transient colonization. Median survival after transplantation was not different between patients with transient colonization who did not receive treatment and those who never had NTM isolated. CONCLUSION: Episodic isolation of NTM from lung transplant recipients is common. Most isolates occur among asymptomatic patients and are transient. Rapidly growing NTM can cause significant SSI, which may be difficult to cure. NTM disease rate is higher among lung transplant recipients than in the general population. In this cohort, NTM isolation was not associated with increased post transplantation mortality. PMID- 22676721 TI - High-impact loading on the skeleton is associated with a decrease in glucose levels in young men. AB - OBJECTIVE: The skeleton has been suggested to be involved in energy metabolism through osteocalcin (OC), an osteoblast-specific molecule. The objective of this study was to investigate whether high-impact (HI) exercise stimulating bone formation would lead to changes in glucose and lipid metabolism independent of cardiorespiratory effects and whether OC mediates this association. DESIGN: Prospective intervention study. METHODS: Fifty men aged 20-32 years were allocated to an intervention group or a control group. The intervention group completed six different types of jumps in sets of five, with the frequency of these exercises gradually increasing over 8 weeks. At baseline and after 8 weeks, glycerol concentrations were measured in fat tissue as a marker of lipolysis using microdialysis. Blood samples were assayed for OC and markers of glucose and lipid metabolism. Physical activity was measured using an accelerometer. RESULTS: After adjustment for confounders at baseline and changes in physical activity during the intervention period, the intervention was associated with a decrease in levels of glucose (P = 0.04), adrenalin (P = 0.03) and OC (P = 0.04) after adjusting for baseline levels and changes in physical activity. No other differences between the groups were significant, although the trends of the metabolic variables favoured the intervention group. CONCLUSIONS: The results of this study suggest that HI loading on the skeleton may affect glucose metabolism independent of the level of aerobic exercise. PMID- 22676719 TI - Multiscale modeling of double-helical DNA and RNA: a unification through Lie groups. AB - Several different mechanical models of double-helical nucleic-acid structures that have been presented in the literature are reviewed here together with a new analysis method that provides a reconciliation between these disparate models. In all cases, terminology and basic results from the theory of Lie groups are used to describe rigid-body motions in a coordinate-free way, and when necessary, coordinates are introduced in a way in which simple equations result. We consider double-helical DNAs and RNAs which, in their unstressed referential state, have backbones that are either straight, slightly precurved, or bent by the action of a protein or other bound molecule. At the coarsest level, we consider worm-like chains with anisotropic bending stiffness. Then, we show how bi-rod models converge to this for sufficiently long filament lengths. At a finer level, we examine elastic networks of rigid bases and show how these relate to the coarser models. Finally, we show how results from molecular dynamics simulation at full atomic resolution (which is the finest scale considered here) and AFM experimental measurements (which is at the coarsest scale) relate to these models. PMID- 22676722 TI - Influence of fetal glutathione S-transferase copy number variants on adverse reproductive outcomes. AB - A nested case-control association study was designed to investigate the influence of maternal and fetal copy number variants (CNVs) on reproductive outcomes. Genotypes of ten CNVs encompassing GST and CYP genes were assessed. Significant associations were only found for child CNV genotypes. In particular, the child GSTM1 insertion allele was associated with prematurity protection (odds ratio, 95% CI: 0.67, 0.51-0.89; P < 0.01), whereas the child GSTT2B insertion allele was associated with an increased risk of being small for gestational age (odds ratio, 95% CI: 1.33, 1.07-1.67; P = 0.01). The study highlights the role of the fetal genome in prenatal development and also the need to analyse CNVs in a systematic manner. PMID- 22676723 TI - Enhancing physical activity in older adults receiving hospital based rehabilitation: a phase II feasibility study. AB - BACKGROUND: Older adults receiving inpatient rehabilitation have low activity levels and poor mobility outcomes. Increased physical activity may improve mobility. The objective of this Phase II study was to evaluate the feasibility of a randomized controlled trial (RCT) of enhanced physical activity in older adults receiving rehabilitation. METHODS: Patients admitted to aged care rehabilitation with reduced mobility were randomized to receive usual care or usual care plus additional physical activity, which was delivered by a physiotherapist or physiotherapy assistant. The feasibility and safety of the proposed RCT protocol was evaluated. The primary clinical outcome was mobility, which was assessed on hospital admission and discharge by an assessor blinded to group assignment. To determine the most appropriate measure of mobility, three measures were trialled; the Timed Up and Go, the Elderly Mobility Scale and the de Morton Mobility Index. RESULTS: The protocol was feasible. Thirty-four percent of people admitted to the ward were recruited, with 47 participants randomised to a control (n = 25) or intervention group (n = 22). The rates of adverse events (death, falls and readmission to an acute service) did not differ between the groups. Usual care therapists remained blind to group allocation, with no change in usual practice. Physical activity targets were met on weekdays but not weekends and the intervention was acceptable to participants. The de Morton Mobility Index was the most appropriate measure of mobility. CONCLUSIONS: The proposed RCT of enhanced physical activity in older adults receiving rehabilitation was feasible. A larger multi-centre RCT to establish whether this intervention is cost effective and improves mobility is warranted. TRIAL REGISTRATION: The trial was registered with the ANZTCR (ACTRN12608000427370). PMID- 22676724 TI - Charge transport through graphene junctions with wetting metal leads. AB - Graphene is believed to be an excellent candidate material for next-generation electronic devices. However, one needs to take into account the nontrivial effect of metal contacts in order to precisely control the charge injection and extraction processes. We have performed transport calculations for graphene junctions with wetting metal leads (metal leads that bind covalently to graphene) using nonequilibrium Green's functions and density functional theory. Quantitative information is provided on the increased resistance with respect to ideal contacts and on the statistics of current fluctuations. We find that charge transport through the studied two-terminal graphene junction with Ti contacts is pseudo-diffusive up to surprisingly high energies. PMID- 22676725 TI - Expression of scavenger receptor A on antigen presenting cells is important for CD4+ T-cells proliferation in EAE mouse model. AB - BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) characterized by damage to the neuronal myelin sheath. One of the key effectors for inflammatory injury is the antigen-presenting cell (APC). The class A scavenger receptor (SRA), constitutively expressed by APCs, such as macrophages and dendritic cells in peripheral tissues and the CNS, was shown to play a role in the phagocytosis of myelin; however, the role of SRA in the development of experimental autoimmune encephalomyelitis (EAE) and autoimmune reaction in the periphery has not yet been studied. METHODS: We investigated EAE progression in wild-type (WT) vs. SRA-/- mice using clinical score measurements and characterized CNS pathology using staining. Furthermore, we assessed SRA role in mediating anti myelin pro-inflammatory response in cell cultures. RESULTS: We discovered that EAE progression and CNS demyelination were significantly reduced in SRA-/- mice compared to WT mice. In addition, there was a reduction of infiltrating peripheral immune cells, such as T cells and macrophages, in the CNS lesion of SRA-/- mice, which was associated with reduced astrogliosis. Immunological assessment showed that SRA deficiency resulted in significant reduction of pro-inflammatory cytokines that play a major role in EAE progression, such as IL-2, IFN-gamma, IL-17 and IL-6. Furthermore, we discovered that SRA-/- APCs showed impairments in activation and in their ability to induce pro-inflammatory CD4+ T cell proliferation. CONCLUSION: Expression of SRA on APCs is important for CD4+ T-cells proliferation in EAE mouse model. Further studies of SRA-mediated cellular pathways in APCs may offer useful insights into the development of MS and other autoimmune diseases, providing future avenues for therapeutic intervention. PMID- 22676770 TI - Changes in intrapopulation resource use patterns of an endangered raptor in response to a disease-mediated crash in prey abundance. AB - 1. A long-standing question in ecology is how natural populations respond to a changing environment. Emergent optimal foraging theory-based models for individual variation go beyond the population level and predict how its individuals would respond to disturbances that produce changes in resource availability. 2. Evaluating variations in resource use patterns at the intrapopulation level in wild populations under changing environmental conditions would allow to further advance in the research on foraging ecology and evolution by gaining a better idea of the underlying mechanisms explaining trophic diversity. 3. In this study, we use a large spatio-temporal scale data set (western continental Europe, 1968-2006) on the diet of Bonelli's Eagle Aquila fasciata breeding pairs to analyse the predator trophic responses at the intrapopulation level to a prey population crash. In particular, we borrow metrics from studies on network structure and intrapopulation variation to understand how an emerging infectious disease [the rabbit haemorrhagic disease (RHD)] that caused the density of the eagle's primary prey (rabbit Oryctolagus cuniculus) to dramatically drop across Europe impacted on resource use patterns of this endangered raptor. 4. Following the major RHD outbreak, substantial changes in Bonelli's Eagle's diet diversity and organisation patterns at the intrapopulation level took place. Dietary variation among breeding pairs was larger after than before the outbreak. Before RHD, there were no clusters of pairs with similar diets, but significant clustering emerged after RHD. Moreover, diets at the pair level presented a nested pattern before RHD, but not after. 5. Here, we reveal how intrapopulation patterns of resource use can quantitatively and qualitatively vary, given drastic changes in resource availability. 6. For the first time, we show that a pathogen of a prey species can indirectly impact the intrapopulation patterns of resource use of an endangered predator. PMID- 22676771 TI - Miglustat therapy in the French cohort of paediatric patients with Niemann-Pick disease type C. AB - BACKGROUND: Niemann-Pick disease type C (NP-C) is a rare neurovisceral lysosomal lipid storage disease characterized by progressive neurological deterioration. Published data on the use of miglustat in paediatric patients in clinical practice settings are limited. We report findings from a prospective open-label study in the French paediatric NP-C cohort. METHODS: Data on all paediatric NP-C patients treated with miglustat in France between October 2006 and December 2010 were compiled. All patients had a confirmed diagnosis of NP-C, and received miglustat therapy according to manufacturer's recommendations. Pre-treatment and follow-up assessments were conducted according to a standardized protocol. RESULTS: Twenty children were enrolled; 19 had NPC1 gene mutations and 1 had NPC2 gene mutations. The median age at diagnosis was 1.5 years, and the median age at miglustat initiation was 6.0 years. Eight NPC1 patients had the early-infantile, eight had the late-infantile, and three had the juvenile-onset forms of NP-C. A history of hepatosplenomegaly and/or other cholestatic symptoms was recorded in all 8 early-infantile onset patients, 3/8 late-infantile patients, and 1/3 juvenile onset patients. Brain imaging indicated white matter abnormalities in most patients. The median (range) duration of miglustat therapy was 1.3 (0.6-2.3) years in early-infantile, 1.0 (0.8-5.0) year in late-infantile, and 1.0 (0.6-2.5) year in juvenile onset patients. NP-C disability scale scores indicated either stabilization or improvement of neurological manifestations in 1/8, 6/8, and 1/3 NPC1 patients in these subgroups, respectively. There were no correlations between brain imaging findings and disease course. Mild-to-moderate gastrointestinal disturbances were frequent during the first 3 months of miglustat therapy, but were easily managed with dietary modifications and/or anti propulsive medication. CONCLUSIONS: Miglustat can improve or stabilize neurological manifestations in paediatric patients with the late-infantile and juvenile-onset forms of NP-C. Among early-infantile onset patients, a shorter delay between neurological disease onset and miglustat initiation was associated with an initial better therapeutic outcome in one patient, but miglustat did not seem to modify overall disease course in this subgroup. More experience is required with long-term miglustat therapy in early-infantile onset patients treated from the very beginning of neurological manifestations. PMID- 22676718 TI - Sex differences in the neural mechanisms mediating addiction: a new synthesis and hypothesis. AB - In this review we propose that there are sex differences in how men and women enter onto the path that can lead to addiction. Males are more likely than females to engage in risky behaviors that include experimenting with drugs of abuse, and in susceptible individuals, they are drawn into the spiral that can eventually lead to addiction. Women and girls are more likely to begin taking drugs as self-medication to reduce stress or alleviate depression. For this reason women enter into the downward spiral further along the path to addiction, and so transition to addiction more rapidly. We propose that this sex difference is due, at least in part, to sex differences in the organization of the neural systems responsible for motivation and addiction. Additionally, we suggest that sex differences in these systems and their functioning are accentuated with addiction. In the current review we discuss historical, cultural, social and biological bases for sex differences in addiction with an emphasis on sex differences in the neurotransmitter systems that are implicated. PMID- 22676776 TI - Supervisory control of multiple robots in dynamic tasking environments. AB - A military targeting environment was simulated to examine the effects of an intelligent route-planning agent RoboLeader, which could support dynamic robot re tasking based on battlefield developments, on the performance of robotics operators. We manipulated the level of assistance (LOAs) provided by RoboLeader as well as the presence of a visualisation tool that provided feedback to the participants on their primary task (target encapsulation) performance. Results showed that the participants' primary task benefited from RoboLeader on all LOAs conditions compared to manual performance; however, visualisation had little effect. Frequent video gamers demonstrated significantly better situation awareness of the mission environment than did infrequent gamers. Those participants with higher spatial ability performed better on a secondary target detection task than did those with lower spatial ability. Finally, participants' workload assessments were significantly lower when they were assisted by RoboLeader than when they performed the target entrapment task manually. Practitioner Summary: This study demonstrated the utility of an intelligent agent for enhancing robotics operators' supervisory control performance as well as reducing their workload during a complex urban scenario involving moving targets. The results furthered the understanding of the interplay among level-of-autonomy, multitasking performance and individual differences in military tasking environments. PMID- 22676775 TI - Needlestick and sharps injuries among housekeeping workers in hospitals of Shiraz, Iran. AB - BACKGROUND: Needlestick and sharps injuries (NSSIs) are one of the major risk factors for blood-borne infections (BBPs) at healthcare facilities. This study examines the current prevalence of NSSIs among housekeeping workers engaged in the handling and disposal of biomedical waste (BMW) at government and private hospitals in Shiraz, Iran, and furthermore, explores strategies for preventing these injuries. FINDINGS: Using a cross-sectional study design, NSSI's and associated protective measures for housekeeping workers throughout hospitals in Shiraz were evaluated from 2009 onwards. Using a questionnaire, data was collected for 92 workers who had engaged directly with BMW. Data was analyzed using Chi-square, student t-test and where appropriate, SPSS version 12. 90.2 % of housekeeping workers were warned of the dangers associated with waste, 87.5 % in government and 93.2 % in private hospitals (P = 0.0444). 83.7 % had attended educational programs on biomedical waste (BMW) management and injury prevention at their hospital in the preceding year. 16.3 % had not been trained in biomedical waste management (P = 0.0379) and 88.9 % had a sufficient supply of safety wear. CONCLUSIONS: NSSIs are a common risk factor for infection among health care workers within hospitals in Iran. For the effective prevention of these injuries, health boards and hospital trusts need to formulate strategies to improve the working conditions of health care workers, discourage the excessive use of injections, and increase their adherence to universal precautions. PMID- 22676777 TI - The use of drama to support reflection and understanding of the residents' situation in dementia care: a pilot study. AB - BACKGROUND: One key aspect of person-centredness is striving to understand both the patients' experiences and behaviours from their perspective. These aspects are precisely those that staff in dementia care highlight as causing them most difficulty because the people in their care have major problems expressing themselves. There is thus a need to develop a method to help the staff to achieve interpretation through reflection. AIM: The aim of this study was to explore the use of drama as a tool to support reflection among staff working in the residential care of people with dementia. DESIGN: A qualitative evaluation of a programme consisting of three drama sessions with staff working in residential care (n = 10 nurse assistants). METHODS: Data comprised observations and tape recordings of the sessions, the researchers' reflections after each session and a focus-group interview with the participants. The texts were analysed using qualitative content analysis. RESULTS: The analysis showed that: (i) the exercises stimulate reflection about daily caring practice; (ii) the participants must receive extensive information about the purpose of the sessions; (iii) the research team must secure the defined frames and conditions and have practical knowledge about caring for people with dementia and (iv) the management needs to be stable, committed and supportive. CONCLUSION: Drama seems to be a valid tool to aid reflection, but several adjustments are needed concerning both the content of the sessions and the methodology. When designing a larger intervention study, it would be preferable to the sessions to be combined with staff support to effect changes in care provision resulting from their increased awareness of the residents' situation and experience. IMPLICATIONS FOR PRACTICE: Our results showed that drama can be a means to enhance reflection among staff in residential care for people with dementia. Further research is however needed concerning the effects for the staff's situation and nursing care quality. PMID- 22676779 TI - Introduction: starting one's first group. PMID- 22676778 TI - Right Kocher's incision: a feasible and effective incision for right hemicolectomy: a retrospective study. AB - BACKGROUND: The choice of surgical incision is determined by access to the surgical field, particularly when an oncological resection is required. Special consideration is also given to other factors, such as postoperative pain and its sequelae, fewer complications in the early postoperative period and a lower occurrence of incisional hernias. The purpose of this study is to compare the right Kocher's and the midline incision, for patients undergoing right hemicolectomy, by focusing on short- and longterm results. METHODS: Between 1995 and 2009, hospital records for 213 patients that had undergone a right hemicolectomy for a right- sided adenocarcinoma were retrospectively studied. 113 patients had been operated via a Kocher's and 100 via a midline incision. Demographic details, operative data (explorative access to the peritoneal cavity, time of operation), recovery parameters (time with IV analgesic medication, time to first oral fluid intake, time to first solid meal, time to discharge), and oncological parameters (lymph node harvest, TNM stage and resection margins) were analyzed. Postoperative complications were also recorded. The two groups were retrospectively well matched with respect to demographic parameters and oncological status of the tumor. RESULTS: The median length of the midline incision was slightly longer (12 vs. 10 cm, p < 0.05). The duration of the surgery for the Kocher's incision group was significantly shorter (median time 70 vs 85 min, p < 0.001). In three patients we performed wedge resection of liver metastasis and in one patient we performed a typical right hepatectomy that lasted 190 min. No major operative complications were noted. There was no immediate or 30- day postoperative mortality. The Kocher's incision group had a significantly shorter hospital stay (median time 5 vs 8 days). All patients underwent wide tumor excision and clear resection margins were obtained in all cases. No significant difference was noted regarding analgesia requirements and early postoperative complications. Late postoperative complications included 2 incisional hernias and three patients presented with one episode of obstructive ileus, that resolved conservatively. CONCLUSIONS: The Kocher's incision approach for right- sided colon cancer is technically feasible, safe and overall very well tolerated. It can achieve the same standards of tumor resection and surgical field accessibility as the midline approach, while reducing postoperative recovery. PMID- 22676780 TI - ?'Ber?ing' it all. AB - Revealing ourselves in a psychotherapy group, as well as bearing witness to what others reveal, encourages trust among group members and increases our ability to access knowledge, our feelings, our intuitions, and our imaginations. The author, a trainee in a postgraduate group psychotherapy program, describes some of her initial experiences as a group member in a process group and as a group leader. Bearing the experience of being bare in a psychotherapy group, as a member or as a leader, is no easy task. The various meanings of bare and bear as it relates to group participation are explored in this paper through the analysis of the author's dream and through other personal and professional anecdotes. PMID- 22676781 TI - Vitalizing the group--and me. AB - Emotional liveliness in a psychotherapy group can take various forms. Maintaining this liveliness can be a challenging task in a group, particularly when both the patients and the therapist face deeply rooted inhibitions, including fears about competition, being judged, and being destructive. The author of this paper, a candidate and group member in a postdoctoral group psychotherapy training program, recounts some of her experiences as the leader of a newly formed and developing group, particularly as they relate to her efforts to become and remain a "libidinal" (i.e., life or vital force) leader, despite the impact of the group members' and her own anxieties. Clinical anecdotes and insights about the author's own growth, both personally and professionally, as they relate to establishing and maintaining vitality are presented. PMID- 22676782 TI - Compulsive "helpfulness": or, how I learned to stop working so hard and love the group. AB - Compulsive helpfulness, an anxiety-laden need by the therapist to feel helpful, akin to the notion of rescuing others, is a potential pitfall in developing an effective psychotherapy group. It can be regarded variously: (1) as a reaction formation against feelings of boredom and frustration stimulated by such phenomena as group resistance or the enactment of inauthentic relationships in the group; (2) as a therapist style driven by a transferential reaction to be regarded as competent and worthy; (3) as an induced countertransference enactment tied to group members' frustration and passivity about their own interpersonal inadequacies; (4) and as a manic defense against despair over the feeling that one's loving has not done any good. In this essay, the author explores his struggle to identify and come to terms with compulsive helpfulness as a dominant theme in the early stages of his tenure as leader of a psychotherapy group. PMID- 22676783 TI - The anti-candidate considers starting a group. AB - The hurdles to starting a group reside primarily in the therapist. The author shares how her unformulated dread in beginning a private practice psychotherapy group was enacted and then transformed by the group training process itself. The discussion illustrates how disavowed affects-and affects of disavowal-were contained for eventual understanding and growth within the curative embrace of the training group. PMID- 22676784 TI - Beginning a group with beginner's mind. PMID- 22676785 TI - Transforming the professional self. PMID- 22676786 TI - A therapist of the "whole": four reflections as "one". PMID- 22676787 TI - Disability and countertransference in group psychotherapy: connecting social oppression with the clinical frame. AB - Psychoanalysis has paid limited attention to disability, and at times the approach has lacked political awareness. Over recent decades the international disability rights movement has argued that disabled people constitute an oppressed, systemically disadvantaged minority. Lately, a critical psychoanalytic view has connected disablist discrimination to universal unconscious conflicts evoked by impairment. Corresponding evocations emerge in the therapeutic frame, producing countertransference responses to the impaired body. Drawing on psychoanalytically oriented group psychotherapy with severely physically impaired adults, countertransference phenomena were studied in developing discussion on disability-related clinical work. The complex, uncertain role of psychoanalytic practice in combating oppression was also examined. Key issues include challenges to the traditional frame, the crossing of psychic boundaries, anxieties relating to not knowing, and the role of unconscious factors in marginalizing disabled experience. PMID- 22676788 TI - Long-term improvement in coping skills following multimodal treatment in war veterans with chronic PTSD. AB - Due to the long-lasting and resistant symptoms characteristic of chronic combat posttraumatic stress disorder (PTSD), its treatment is complex and often requires a tailored therapeutic approach incorporating both psychotherapy and pharmacotherapy. A multimodal approach of psychoeducative, sociotherapeutic, and dynamically oriented trauma-focused groups is described. We assessed the short- and long-term effectiveness of this therapeutic program by monitoring its impact on PTSD symptoms, depression, neurotic symptoms, coping skills, and quality of life for three years. The findings revealed short-term reduction in the symptoms of PTSD and depression, while the long-term results were manifested as the increased use of all coping mechanisms and a greater level of obsession. PMID- 22676789 TI - Oppression, freedom, and recognition in an analytic therapy group: group and therapist interactions from relational and group analytic perspectives. AB - Group analytic and relational writings point to the development of mutual recognition between individuals as a main treatment goal. To achieve this, it is necessary to face up to issues of control and oppression in the therapeutic relationship, particularly as enacted by the therapist. The relationship between the therapist and group members is a co-construction, shaped by their respective subjectivities. The therapist's willingness to enter into an open examination of his or her enactments can stimulate change in relationships with patients, resulting in freer and more spontaneous communication in the group. To illustrate, several sessions of an analytic therapy group are presented in which there were struggles between (1) the desire for equality and mutuality and (2) firm exercise of authority. PMID- 22676790 TI - Processes and outcomes in prevention-focused time-limited groups for girls. AB - Processes and outcomes in 8-week prevention-focused, school-based groups for preadolescent girls were assessed in a naturalistic study. Specifically, whether such groups would facilitate their social-emotional development and whether affiliative processes in the groups were related to outcome were explored. In addition to expecting the groups to be effective, it was hypothesized that affiliative processes would be directly related to outcome and, more particularly, that increased positive affiliative feelings from the group toward the individual would be more predictive of positive treatment outcome than increased positive feelings from the individual toward the group. While findings did not support these hypotheses linking process to outcome, ancillary analyses revealed that different patterns of affiliation over time (i.e., U-shape pattern versus inverted U-shape pattern) distinguished the high- versus low-outcome participants, respectively. PMID- 22676792 TI - Group therapy for patients suffering from eating disorders. PMID- 22676797 TI - Consumption of dairy products and associations with incident diabetes, CHD and mortality in the Whitehall II study. AB - Few prospective studies have examined the effects of different types of dairy food on the risks of type 2 diabetes, CHD and mortality. We examined whether intakes of total dairy, high-fat dairy, low-fat dairy, milk and fermented dairy products were related to these outcomes in the Whitehall II prospective cohort study. At baseline, dairy consumption was assessed by FFQ among 4526 subjects (72% men) with a mean age 56 (sd 6) years. Death certificates and medical records were used to ascertain CHD mortality and non-fatal myocardial infarction. Incident diabetes was detected by the oral glucose tolerance test or self-report. Incidence data were analysed using Cox proportional hazards models, adjusted for lifestyle and dietary factors. During approximately 10 years of follow-up, 273 diabetes, 323 CHD and 237 all-cause mortality cases occurred. In multivariable models, intakes of total dairy and types of dairy products were not significantly associated with incident diabetes or CHD (all P values for trend >0.1). Fermented dairy products was inversely associated with overall mortality (hazard ratios approximately 0.7 in the middle and highest tertiles; P for trend < 0.01) but not with incident CHD or diabetes (P>0.3). In conclusion, intakes of total dairy and types of dairy products showed no consistent relationship with incident diabetes, CHD or all-cause mortality. PMID- 22676798 TI - Classification and characterization of manuka honeys based on phenolic compounds and methylglyoxal. AB - Manuka honey from New Zealand is often considered to be a medicinal product of special value due to its high level of antimicrobial activity. Therefore, the distinct authentication of its botanical origin is of great importance. Aside from the common pollen analysis, it is in this respect particularly the analysis of the phenolic acids, flavonoids, and norisoprenoids that is described as useful. In the present study, numerous manuka honeys were analyzed by UPLC-PDA MS/MS after solid-phase extraction and compared to other kinds of honey to define marker substances characteristic for manuka honeys. The PDA profiles obtained differed markedly from each other so that the individual honey samples could be assigned to three groups. For the honeys of group 1 the comparably high concentrations of 4-hydroxybenzoic acid, dehydrovomifoliol, and benzoic acid proved to be typical, whereas the profiles of group 2 showed high kojic acid and 2-methoxybenzoic acid intensities. The manuka honeys of group 3, on the other hand, yielded high amounts of syringic acid, 4-methoxyphenyllactic acid, and methyl syringate. Furthermore, the comprehensive comparison of manuka honeys to other unifloral honeys revealed that especially kojic acid, 5-methyl-3 furancarboxylic acid, leptosin, unedone, 2-methoxybenzoic acid, 4 methoxyphenyllactic acid, 3-hydroxy-1-(2-methoxyphenyl)penta-1,4-dione, and methyl syringate were useful for distinguishing manuka honeys from the other kinds of investigated honeys. Moreover, kojic acid, unedone, 5-methyl-3 furancarboxylic acid, 3-hydroxy-1-(2-methoxyphenyl)penta-1,4-dione, and lumichrome were identified in manuka honey for the first time. PMID- 22676799 TI - Stress-related depression: neuroendocrine, genetic, and therapeutical aspects. AB - OBJECTIVE: To summarize current concepts on neuroendocrine and genetic principles underlying stress-related depression and to discuss the challenges of personalized treatment in depression. METHODS: Review of the literature pertaining to genetic and neuroendocrine basis of stress-related depression including aspects of treatment response with a focus on the hypothalamus pituitary-adrenal (HPA) axis. RESULTS: There is increasing evidence that genetic polymorphisms and dysregulation of the HPA axis are associated with the pathophysiology of stress-related depression. Individual stress hormone reactivity seems to be determined by a combination of genetic and environmental factors, contributing to both, resilience or vulnerability. CONCLUSIONS: Although substantial progress has been made, current knowledge is still limited. Further basic and clinical research is needed to identify specific subgroups and to minimize heterogeneity of the depression phenotype. A better characterization is essential to detect genetic and functional predictors of antidepressant treatment response to follow the vision of personalized therapy in psychiatry. PMID- 22676800 TI - Differential regulation of antibiotic biosynthesis by DraR-K, a novel two component system in Streptomyces coelicolor. AB - A novel two-component system (TCS) designated as DraR-K (sco3063/sco3062) was identified to be involved in differential regulation of antibiotic biosynthesis in Streptomyces coelicolor. The S. coelicolor mutants with deletion of either or both of draR and draK exhibited significantly reduced actinorhodin (ACT) but increased undecylprodigiosin (RED) production on minimal medium (MM) supplemented separately with high concentration of different nitrogen sources. These mutants also overproduced a yellow-pigmented type I polyketide (yCPK) on MM with glutamate (Glu). It was confirmed that DraR-K activates ACT but represses yCPK production directly through the pathway-specific activator genes actII-ORF4 and kasO, respectively, while its role on RED biosynthesis was independent of pathway specific activator genes redD/redZ. DNase I footprinting assays revealed that the DNA binding sites for DraR were at -124 to -98 nt and -24 to -1 nt relative to the respective transcription start point of actII-ORF4 and kasO. Comparison of the binding sites allowed the identification of a consensus DraR-binding sequence, 5'-AMAAWYMAKCA-3' (M: A or C; W: A or T; Y: C or T; K: G or T). By genome screening and gel-retardation assay, 11 new targets of DraR were further identified in the genome of S. coelicolor. Functional analysis of these tentative targets revealed the involvement of DraR-K in primary metabolism. DraR-K homologues are widely spread in different streptomycetes. Interestingly, deletion of draR-Ksav (sav_3481/sav_3480, homologue of draR-K) in the industrial model strain S. avermitilis NRRL-8165 led to similar abnormal antibiotic biosynthesis, showing higher avermectin while slightly decreased oligomycin A production, suggesting that DraR-K-mediated regulation system might be conserved in streptomycetes. This study further reveals the complexity of TCS in regulation of antibiotic biosynthesis in Streptomyces. PMID- 22676801 TI - Retrospective, propensity score-matched cohort study examining timing of fracture fixation for traumatic thoracolumbar fractures. AB - The timing of surgery in patients with traumatic thoracic/thoracolumbar fractures, with or without spinal cord injury, remains controversial. The objective of this study was to determine the importance of the timing of surgery for complications and resource utilization following fixation of traumatic thoracic/thoracolumbar fractures. In this retrospective cohort study, the 2003 2008 California Inpatient Databases were searched for patients receiving traumatic thoracic/thoracolumbar fracture fixation. Patients were classified as having early (<72 h) or late (>72 h) surgery. Propensity score modeling produced a matched cohort balanced on age, comorbidity, trauma severity, and other factors. Complications, mortality, length of stay, and hospital charges were assessed. Multivariate logistic regression was used to determine the impact of delayed surgery on in-hospital complications after balancing and controlling for other important factors. Early surgery (<72 h) for traumatic thoracic/thoracolumbar fractures was associated with a significantly lower overall complication rate (including cardiac, thromboembolic, and respiratory complications), and decreased hospital stay. In-hospital charges were significantly lower ($38,120 difference) in the early surgery group. Multivariate analysis identified time to surgery as the strongest predictor of in-hospital complications, although age, medical comorbidities, and injury severity score were also independently associated with increased complications. We reinforce the beneficial impact of early spinal surgery (prior to 72 h) in traumatic thoracic/thoracolumbar fractures to reduce in-hospital complications, hospital stay, and resource utilization. These results provide further support to the emerging literature and professional consensus regarding the importance of early thoracic/thoracolumbar spine stabilization of traumatic fractures to improve patient outcomes and limit hospitalization costs. PMID- 22676802 TI - Temporal changes in milk proteomes reveal developing milk functions. AB - Human milk proteins provide essential nutrition for growth and development, and support a number of vital developmental processes in the neonate. A complete understanding of the possible functions of human milk proteins has been limited by incomplete knowledge of the human milk proteome. In this report, we have analyzed the proteomes of whey from human transitional and mature milk using ion exchange and SDS-PAGE based protein fractionation methods. With a larger-than normal sample loading approach, we are able to largely extend human milk proteome to 976 proteins. Among them, 152 proteins are found to render significant regulatory changes between transitional milk and mature milk. We further found that immunoglobulins sIgA and IgM are more abundant in transitional milk, whereas IgG is more abundant in mature milk, suggesting a transformation in defense mechanism from newborns to young infants. Additionally, we report a more comprehensive view of a complement system and associated regulatory apparatus in human milk, demonstrating the presence and function of a system similar to that found in the circulation but prevailed by alternative pathway in complement activation. Proteins involved in various aspects of carbohydrate metabolism are also described, revealing either a transition in milk functionality to accommodate carbohydrate-rich secretions as lactation progresses, or a potentially novel way of looking at the metabolic state of the mammary tissue. Lately, a number of extracellular matrix (ECM) proteins are found to be in higher abundance in transitional milk and may be relevant to the development of infants' gastrointestinal tract in early life. In contrast, the ECM protein fibronectin and several of the actin cytoskeleton proteins that it regulates are more abundant in mature milk, which may indicate the important functional role for milk in regulating reactive oxygen species. PMID- 22676803 TI - High school allied health students and their exposure to the profession of EMS. AB - INTRODUCTION: Ensuring a stable Emergency Medical Services (EMS) workforce is a growing concern, and effective recruiting strategies are needed to expose young adults to the EMS profession. The objective of this study was to assess the exposure of high school allied health students to EMS as a career option, as well as measure their attitudes and beliefs about the EMS profession. Hypothesis Few high school allied health students are exposed to EMS educational and career opportunities. METHODS: A convenience sample of allied health students in a rural high school system was surveyed about exposure to EMS, career intentions, factors impacting career decisions, and attitudes and beliefs about EMS. Descriptive statistics were calculated, and intention to pursue an EMS career was modeled using logistic regression. RESULTS: Of 171 students enrolled in allied health courses across six high schools, 135 (78.9%) agreed to participate; 85.2% were female. Almost all (92.6%) respondents intended to pursue a health career, but only 43.0% reported that their allied health course exposed them to EMS as a profession. Few participants (37.7%) were knowledgeable about EMS associate degree or baccalaureate degree (27.4%) programs. Only 20.7% of the respondents intended to pursue EMS as a career, although 46.0% wanted to learn more about the profession. Most (68.2%) students expressed interest in an emergency medical technician (EMT) course if one were offered, and 80.0% were interested in a ride along program. Independent predictors of pursuing an EMS career included exposure to EMS outside of high school (OR = 7.4, 95% CI = 1.7-30.4); media influence on career choice (OR = 9.6, 95% CI = 1.8-50.1); and the belief that EMS was mentally challenging (OR = 15.9, 95% CI = 1.1-216.6). Negative predictors included the beliefs that an EMS career was stimulating (OR = 0.05, 95% CI = 0.00-0.53) and physically challenging (OR = 0.06, 95% CI = 0.00-0.63); as well as prior exposure to an EMS job advertisement (OR = 0.14, 0.03-0.53). CONCLUSIONS: Overall, there was a lack of exposure to career and educational options in EMS among allied health students in the school system studied, and few students intended to pursue an EMS career after graduation. However, the majority of students indicated they would like to learn more about EMS, and would enroll in an EMT course and ride along program if available. These findings suggest that, with exposure to the profession, more allied health students could choose EMS as a career. PMID- 22676804 TI - Pulsed electromagnetic field: an organic compatible method to promote plant growth and yield in two corn types. AB - Pre-sowing treatment of pulsed electromagnetic fields was used in corn seeds, in both indoor and outdoor conditions, in order to investigate the effect on plant growth and yield. The results of this research showed that pulsed electromagnetic fields can enhance plant characteristics, both under controlled environmental conditions and uncontrolled field conditions. The two varieties responded differently in the duration of magnetic field. Seeds were treated for 0, 15, 30, and 45 min with pulsed electromagnetic field (MF-0, MF-15, MF-30, and MF-45). Common corn variety performed better results in MF-30 treatment, while sweet corn variety performed better in MF-45 treatment. Magnetic field improved germination percentage, vigor, chlorophyll content, leaf area, plant fresh and dry weight, and finally yields. In the very interesting measurement of yield, seeds that have been exposed to magnetic field for 30 and 45 min have been found to perform the best results with no statistical differences among them. Another interesting finding was in root dry weight measurements, where magnetic field has a negative impact in MF-30 treatment in both hybrids, however without affecting other measurements. Enhancements on plant characteristics with economic impact on producer's income could be the future of a modern, organic, and sustainable agriculture. PMID- 22676805 TI - The appropriateness of, and compliance with, telephone triage decisions: a systematic review and narrative synthesis. AB - AIM: This paper is a report of the synthesis of evidence on the appropriateness of, and compliance with, telephone triage decisions. BACKGROUND: Telephone triage plays an important role in managing demand for health care. Important questions are whether triage decisions are appropriate and patients comply with them. DATA SOURCES: CINAHL, Cochrane Clinical Trials Database, Medline, Embase, Web of Science, and Psyc Info were searched between 1980-June 2010. DESIGN: LITERATURE REVIEW: Rapid Evidence Synthesis. REVIEW METHODS: The principles of rapid evidence assessment were followed. RESULTS: We identified 54 relevant papers: 26 papers reported appropriateness of triage decision, 26 papers reported compliance with triage decision, and 2 papers reported both. Nurses triaged calls in most of the studies (n=49). Triage decisions rated as appropriate varied between 44-98% and compliance ranged from 56-98%. Variation could not be explained by type of service or method of assessing appropriateness. However, inconsistent definitions of appropriateness may explain some variation. Triage decisions to contact primary care may have lower compliance than decisions to contact emergency services or self care. CONCLUSION: Telephone triage services can offer appropriate decisions and decisions that callers comply with. However, the association between the appropriateness of a decision and subsequent compliance requires further investigation and further consideration needs to be given to the minority of calls which are inappropriately managed. We suggest that a definition of appropriateness incorporating both accuracy and adequacy of triage decision should be encouraged. PMID- 22676806 TI - Premature expression of a muscle fibrosis axis in chronic HIV infection. AB - BACKGROUND: Despite the success of highly active antiretroviral therapy (HAART), HIV infected individuals remain at increased risk for frailty and declines in physical function that are more often observed in older uninfected individuals. This may reflect premature or accelerated muscle aging. METHODS: Skeletal muscle gene expression profiles were evaluated in three uninfected independent microarray datasets including young (19 to 29 years old), middle aged (40 to 45 years old) and older (65 to 85 years old) subjects, and a muscle dataset from HIV infected subjects (36 to 51 years old). Using Bayesian analysis, a ten gene muscle aging signature was identified that distinguished young from old uninfected muscle and included the senescence and cell cycle arrest gene p21/Cip1 (CDKN1A). This ten gene signature was then evaluated in muscle specimens from a cohort of middle aged (30 to 55 years old) HIV infected individuals. Expression of p21/Cip1 and related pathways were validated and further analyzed in a rodent model for HIV infection. RESULTS: We identify and replicate the expression of a set of muscle aging genes that were prematurely expressed in HIV infected, but not uninfected, middle aged subjects. We validated select genes in a rodent model of chronic HIV infection. Because the signature included p21/Cip1, a cell cycle arrest gene previously associated with muscle aging and fibrosis, we explored pathways related to senescence and fibrosis. In addition to p21/Cip1, we observed HIV associated upregulation of the senescence factor p16INK4a (CDKN2A) and fibrosis associated TGFbeta1, CTGF, COL1A1 and COL1A2. Fibrosis in muscle tissue was quantified based on collagen deposition and confirmed to be elevated in association with infection status. Fiber type composition was also measured and displayed a significant increase in slow twitch fibers associated with infection. CONCLUSIONS: The expression of genes associated with a muscle aging signature is prematurely upregulated in HIV infection, with a prominent role for fibrotic pathways. Based on these data, therapeutic interventions that promote muscle function and attenuate pro-fibrotic gene expression should be considered in future studies. PMID- 22676807 TI - Abuse from in-laws and associations with attempts to control reproductive decisions among rural women in Cote d'Ivoire: a cross-sectional study. AB - OBJECTIVE: To document the lifetime prevalence of abuse from in-laws (both nonphysical maltreatment and physical violence), the forms of in-law abuse and reproductive control, and the relationship between experiences of in-law abuse and reproductive control among partnered women in rural Cote d'Ivoire. DESIGN: Cross-sectional study using baseline data (October 2010) from a randomised controlled trial examining socio-economic interventions on reduction of violence against Ivorian women. SETTING: Rural Cote d'Ivoire. POPULATION: A total of 981 Ivorian women aged 18 years and older who reported having a male partner and a current source of stable income. METHODS: Bivariate and multivariable logistic regression. MAIN OUTCOME MEASURES: Lifetime, in-law-perpetrated reproductive control. RESULTS: More than one in four (27.0%) women reported experiencing lifetime in-law abuse. In adjusted logistic regression analysis, in-law abuse was significantly associated with in-law-perpetrated reproductive control (adjusted odds ratio 6.9; 95% confidence interval 3.9-12.2; P < 0.0001). Religion and having fewer pregnancies were also associated with reporting in-law-perpetrated reproductive control. CONCLUSIONS: Increased efforts are needed to involve in laws in programmes that seek to reduce gender-based violence against women and improve women's reproductive health. PMID- 22676808 TI - Acute norovirus-induced agranulocytosis in a pediatric kidney transplant recipient. AB - Norovirus (NoV) infection is usually limited to the gastrointestinal (GI) tract. However, in immunocompromised patients, this infection might lead to severe life threatening complications. We herein describe a pediatric kidney transplant patient who presented with an acute NoV infection complicated by febrile agranulocytosis that resolved with improvement of her GI illness. This unusual presentation has not been described before, to our knowledge. The aim of this article is to highlight the sometimes dramatic clinical presentation of NoV infection in immunosuppressed patients, and the importance of including this infection in the differential diagnosis of neutropenia in that specific population. PMID- 22676809 TI - Total lymphocyte count as a surrogate marker for CD4 count in resource-limited settings. AB - BACKGROUND: CD4 testing is the recognized gold standard used to stage HIV/AIDS, guide treatment decisions for HIV-infected persons and evaluate effectiveness of therapy. The need for a less expensive surrogate marker that can be used in resource-limited setting is however necessary. The study sought to assess the suitability of Total lymphocyte count (TLC) as a surrogate marker for CD4 count in resource-limited localities in Ghana. METHODS: This observational study was conducted at the Central Regional Hospital, which has one of the established antiretroviral therapy centres in Ghana. A total of one hundred and eighty-four (184) confirmed HIV I seropositive subjects were included in the study. Blood samples were taken from all the subjects for estimation of CD4 and total lymphocyte counts. The study subjects were further categorised into three (3) groups according to the Centers for Disease Control and Prevention (CDC) classification criteria as follows: CD4 counts (1) >= 500 cells/mm3 (2) 200-499 cells/mm3 and (3) <200 cells/mm3. Positive predictive value (PPV), negative predictive value (NPV), sensitivity and specificity of various TLC cut-offs were computed for three groups. Correlation and Receiver Operator Characteristic analysis was performed for the various CD4 counts and their corresponding Total Lymphocyte count obtained. RESULTS: The sensitivity, specificity, positive and negative predictive values of TLC 1200 cells/ mm3 to predict CD4 count were <200 cells/mm3 72.2%, 100%, 100% and 95.7% respectively. A TLC of 1500 cells/ mm3 was found to have maximal sensitivity (96.67%), specificity (100%), PPV (100%) and NPV (75.0%) for predicting a CD4 cell count of 200-499 cell/mm3. A TLC of 1900 cells/mm3 was also found to have a maximal sensitivity (98.45%), specificity (100%), PPV (100%) and NPV (100%) for predicting CD4 count >=500 cells/mm3. A positive correlation was noted between 184 paired CD4 and TLC counts (r = 0.5728). CONCLUSION: Total Lymphocyte count can therefore adequately serve as a surrogate marker for CD4 count in HIV patients who are naive for antiretroviral therapy in resource-limited areas. PMID- 22676810 TI - Boric acid: a highly efficient catalyst for transamidation of carboxamides with amines. AB - A novel method of transamidation of carboxamides with amines using catalytic amounts of readily available boric acid under solvent-free conditions has been developed. The scope of the methodology has been demonstrated with (i) primary, secondary, and tertiary amides and phthalimide and (ii) aliphatic, aromatic, cyclic, acyclic, primary, and secondary amines. PMID- 22676811 TI - Indomethacin protects rats from neuronal damage induced by traumatic brain injury and suppresses hippocampal IL-1beta release through the inhibition of Nogo-A expression. AB - BACKGROUND: Nogo-A is a member of the reticulon family of membrane-associated proteins and plays an important role in axonal remodeling. The present study aimed to investigate alterations in Nogo-A expression following traumatic brain injury (TBI)-induced inflammation and neuronal damage. METHODS: A weight-drop device was used to deliver a standard traumatic impact to rats. Western blot, RT PCR and ELISA were used to analyze the expression of Nogo-A and IL-1beta. Nogo-A antisense, and an irrelevant control oligonucleotide was intracerebroventricularly infused. We also performed H & E staining and luxol fast blue staining to evaluate the neuronal damage and demyelination resulting from TBI and various treatments. RESULTS: Based on RT-PCR and western blot analyses, the expression of Nogo-A was found to be significantly upregulated in the hippocampus beginning eight hours after TBI. In addition, TBI caused an apparent elevation in IL-1beta levels and severe neuronal damage and demyelination in the tested animals. All of the TBI-associated molecular and cellular consequences could be effectively reversed by treating the animals with the anti-inflammatory drug indomethacin. More importantly, the TBI-associated stimulation in the levels of both Nogo-A and IL-1beta could be effectively inhibited by a specific Nogo-A antisense oligonucleotide. CONCLUSIONS: Our findings suggest that the suppression of Nogo-A expression appears to be an early response conferred by indomethacin, which then leads to decreases in the levels of IL-1beta and TBI-induced neuron damage. PMID- 22676812 TI - Systematic social observation of children's neighborhoods using Google Street View: a reliable and cost-effective method. AB - BACKGROUND: Children growing up in poor versus affluent neighborhoods are more likely to spend time in prison, develop health problems and die at an early age. The question of how neighborhood conditions influence our behavior and health has attracted the attention of public health officials and scholars for generations. Online tools are now providing new opportunities to measure neighborhood features and may provide a cost effective way to advance our understanding of neighborhood effects on child health. METHOD: A virtual systematic social observation (SSO) study was conducted to test whether Google Street View could be used to reliably capture the neighborhood conditions of families participating in the Environmental-Risk (E-Risk) Longitudinal Twin Study. Multiple raters coded a subsample of 120 neighborhoods and convergent and discriminant validity was evaluated on the full sample of over 1,000 neighborhoods by linking virtual SSO measures to: (a) consumer based geo-demographic classifications of deprivation and health, (b) local resident surveys of disorder and safety, and (c) parent and teacher assessments of children's antisocial behavior, prosocial behavior, and body mass index. RESULTS: High levels of observed agreement were documented for signs of physical disorder, physical decay, dangerousness and street safety. Inter-rater agreement estimates fell within the moderate to substantial range for all of the scales (ICCs ranged from .48 to .91). Negative neighborhood features, including SSO-rated disorder and decay and dangerousness corresponded with local resident reports, demonstrated a graded relationship with census-defined indices of socioeconomic status, and predicted higher levels of antisocial behavior among local children. In addition, positive neighborhood features, including SSO-rated street safety and the percentage of green space, were associated with higher prosocial behavior and healthy weight status among children. CONCLUSIONS: Our results support the use of Google Street View as a reliable and cost effective tool for measuring both negative and positive features of local neighborhoods. PMID- 22676813 TI - Resistance trends in gram-negative bacteria: surveillance results from two Mexican hospitals, 2005-2010. AB - BACKGROUND: Hospital-acquired infections caused by multiresistant gram-negative bacteria are difficult to treat and cause high rates of morbidity and mortality. The analysis of antimicrobial resistance trends of gram-negative pathogens isolated from hospital-acquired infections is important for the development of antimicrobial stewardship programs. The information obtained from antimicrobial resistant programs from two hospitals from Mexico will be helpful in the selection of empiric therapy for hospital-acquired gram-negative infections. FINDINGS: Two thousand one hundred thirty two gram-negative bacteria collected between January 2005 and December 2010 from hospital-acquired infections occurring in two teaching hospitals in Mexico were evaluated. Escherichia coli was the most frequently isolated gram-negative bacteria, with >50% of strains resistant to ciprofloxacin and levofloxacin. Klebsiella spp. showed resistance rates similar to Escherichia coli for ceftazidime (33.1% vs 33.2%), but exhibited lower rates for levofloxacin (18.2% vs 56%). Of the samples collected for the third most common gram-negative bacteria, Pseudomonas aeruginosa, >12.8% were resistant to the carbapenems, imipenem and meropenem. The highest overall resistance was found in Acinetobacter spp. Enterobacter spp. showed high susceptibility to carbapenems. CONCLUSIONS: E. coli was the most common nosocomial gram-negative bacilli isolated in this study and was found to have the second-highest resistance to fluoroquinolones (>57.9%, after Acinetobacter spp. 81.2%). This finding represents a disturbing development in a common nosocomial and community pathogen. PMID- 22676817 TI - Ninth Conversation in the Discipline Biomolecular Stereodynamics The University, Albany, New York, June 20-24, 1995. PMID- 22676814 TI - Optimized submerged batch fermentation strategy for systems scale studies of metabolic switching in Streptomyces coelicolor A3(2). AB - BACKGROUND: Systems biology approaches to study metabolic switching in Streptomyces coelicolor A3(2) depend on cultivation conditions ensuring high reproducibility and distinct phases of culture growth and secondary metabolite production. In addition, biomass concentrations must be sufficiently high to allow for extensive time-series sampling before occurrence of a given nutrient depletion for transition triggering. The present study describes for the first time the development of a dedicated optimized submerged batch fermentation strategy as the basis for highly time-resolved systems biology studies of metabolic switching in S. coelicolor A3(2). RESULTS: By a step-wise approach, cultivation conditions and two fully defined cultivation media were developed and evaluated using strain M145 of S. coelicolor A3(2), providing a high degree of cultivation reproducibility and enabling reliable studies of the effect of phosphate depletion and L-glutamate depletion on the metabolic transition to antibiotic production phase. Interestingly, both of the two carbon sources provided, D-glucose and L-glutamate, were found to be necessary in order to maintain high growth rates and prevent secondary metabolite production before nutrient depletion. Comparative analysis of batch cultivations with (i) both L glutamate and D-glucose in excess, (ii) L-glutamate depletion and D-glucose in excess, (iii) L-glutamate as the sole source of carbon and (iv) D-glucose as the sole source of carbon, reveal a complex interplay of the two carbon sources in the bacterium's central carbon metabolism. CONCLUSIONS: The present study presents for the first time a dedicated cultivation strategy fulfilling the requirements for systems biology studies of metabolic switching in S. coelicolor A3(2). Key results from labelling and cultivation experiments on either or both of the two carbon sources provided indicate that in the presence of D-glucose, L glutamate was the preferred carbon source, while D-glucose alone appeared incapable of maintaining culture growth, likely due to a metabolic bottleneck at the oxidation of pyruvate to acetyl-CoA. PMID- 22676819 TI - A comparison of diode laser and Er:YAG lasers in the treatment of gingival melanin pigmentation. AB - OBJECTIVES: This study compared the use of diode and Er:YAG lasers in treating gingival melanin pigmentation (GMP) in terms of gingival depigmentation, local anesthesia requirements, postoperative pain/discomfort, depigmentation effectiveness, and total treatment duration. STUDY DESIGN: Twenty patients (13 female, 7 male) referred with GMP were enrolled in the study. Patients were randomly divided into 2 groups. Group 1 was treated with a gallium aluminum arsenide diode laser with a continuous wavelength of 808 nm, and group 2 was treated with an Er:YAG laser with a continuous wavelength of 2,940 nm. Gingival depigmentation was performed by applying the laser at 1 W. Treatment was administered on a weekly basis until a normal pink gingival color was observable in clinical examination and photographs. In addition, patients were asked to evaluate the procedure by using a self-administered questionnaire. RESULTS: Procedures were carried out without the need for any topical or local anesthetic, and no unpleasant events occurred during the actual procedure or the healing period. The total length of treatment was significantly shorter with the diode laser (group 1) than with the Er:YAG laser (group 2; P < .05). No melanin recurrence was detected during any follow-up session. CONCLUSIONS: Diode and Er:YAG lasers administered at 1 W both result in satisfactory depigmentation of GMP. PMID- 22676820 TI - A preliminary study on the hard-soft tissue relationships among unoperated secondary unilateral cleft nose deformities. AB - OBJECTIVE: The aim of this study was to explore the bone-soft tissue relationships around the nasolabial area in uncorrected secondary unilateral cleft nose deformities. STUDY DESIGN: Measurements taken from photographs and cone-beam computerized tomography (CBCT) results were derived and paired up to represent the deformity features of bone and soft tissue, respectively. RESULTS: All soft tissue measurements were significantly smaller than the corresponding bone measurements. Various bone-soft tissue correlation patterns were observed in different measurement pairs. CONCLUSIONS: The adopted photography-CBCT combined measurement method appeared to be reliable in evaluating the hard-soft tissue relationships in the nasolabial area. In unoperated unilateral cleft nose deformities, bony deformities would decide the soft tissue contours, and soft tissue in turn could camouflage the underlying bone deformities in various patterns and scale, making the external configuration less deformed than its bone basis. PMID- 22676821 TI - Evaluation in vitro of the tensile strength of crimpable hooks used for stabilization in orthognathic surgery. AB - OBJECTIVE: The aim of this study was to evaluate the tensile strength of crimpable hooks used for arch stabilization in orthognatic surgery. STUDY DESIGN: Ninety stainless steel wire (0.019" * 0.026") segments, each measuring 6 cm long, were used and attached to crimpable hooks of different commercial brands. Six groups were formed (n = 10) denominated as follows: control, in which the wire segments were perpendicularly welded by spot welding machine; and the hooks groups M (Morelli), MS (Morelli with weld), TP (TP Ortho), TPS (TP with weld), TPTg (TP-tungsten), TPTgS (TP-tungsten with weld), AO (American Orthodontics), and AOS (American Orthodontics with weld). The test specimen topography was evaluated by scanning electron microscopy before and after the tensile strength tests. After obtaining the results, the analysis of variance and Kruskal-Wallis multiple-comparison tests were applied. RESULTS: Compared with the control group, the AOS ball hooks and those from TPS required a greater amount of force to be displaced along the rectangular arch. The hooks in group M were significantly easier to displace, followed by those from AO. CONCLUSIONS: The best ball hooks for clinical application are those from AOS and TPS. PMID- 22676822 TI - Osteoblast response to porous titanium surfaces coated with zinc-substituted hydroxyapatite. AB - BACKGROUND: The aims of this study were to deposit a zinc-hydroxyapatite (Zn-HA) coating on titanium surfaces by using the electrochemical process and investigate the cell response to the Zn-HA-coated titanium surface. STUDY DESIGN: Surface characteristics were evaluated by scanning electron microscopy (SEM) and inductively coupled plasma atomic emission spectroscopy (ICP-AES). Murine preosteoblast cell (MC3T3-E1) proliferation, alkaline phosphatase (ALP) activity, and osteocalcin release on Zn-HA-coated surfaces were compared with HA-coated surfaces. RESULTS: Field-emission SEM observation showed rod-like HA crystals with a hexagonal cross-section on the HA-coated surface, although the hexagon of the cross-section of Zn-HA crystals became irregular. ICP-AES analysis showed that Zn was present in the Zn-HA coatings at a Zn/(Ca+Zn) molar ratio of 1.04%. Significant increases in cell proliferation, ALP activity on day 7, and osteocalcin production on day 14 (P < .05) were observed for Zn(2+)-containing HA coated surfaces. CONCLUSIONS: The present study showed that a Zn-HA coating deposited by using the electrochemical process enhances proliferation and differentiation of osteoblasts, which has the potential benefit to enhance implant osseointegration. PMID- 22676823 TI - Morphofunctional analysis of sciatic nerve and motor performance of rats after cryotherapy with liquid nitrogen. AB - OBJECTIVE: This work evaluated sciatic nerve regeneration after cryotherapy. STUDY DESIGN: Rats underwent surgical access of the sciatic nerve and subsequent cryotherapy, crush lesion, or no manipulation. Walking-track, electroneuromyographic, and histomorphometric analyses were performed at 15, 30, and 70 postoperative days. RESULTS: At 15 days, the crush and cryotherapy groups showed significant morphofunctional impairment. At 30 days, functional loss was significant in the walking-track, but at 70 days, there were no significant differences between the groups. Amplitude was near zero for the crush group at 15 and 30 days and zero for the cryotherapy group. Measurement of latency was not possible in the latter group. Crush and cryotherapy groups showed greater amounts of myelinated fibers (by 30 days), with axonal diameter and width of the myelin sheath being less than in control group. CONCLUSIONS: Sciatic nerve lesion by application of liquid nitrogen is classified as axonotmesis, which is reversible. PMID- 22676824 TI - Repair of calvarial defects in rabbits with platelet-rich plasma as the scaffold for carrying bone marrow stromal cells. AB - OBJECTIVE: Platelet-rich plasma (PRP) is becoming a new application in tissue engineering and a developing area for clinicians and researchers because it is a natural source of growth factors, many of which can accelerate and promote bone regeneration. However, few studies have reported the potentiality of using PRP as a scaffold in bone tissue engineering. The present study investigated the feasibility of using PRP as a scaffold to carry bone marrow stromal cells (BMSCs) to repair calvarial defects in a rabbit model. STUDY DESIGN: The primary cultured BMSCs were divided into 2 groups. One group was induced with dexamethasone and the other was not induced. Full-thickness bone defects of 5-mm diameter (4 defects per calvarium) were created on the calvaria of 10 New Zealand white rabbits. PRP or whole blood was used, respectively to incorporate the induced or uninduced BMSCs. Then, the composites were activated and applied to repair the defects. The samples were harvested 8 weeks later and bone regeneration was assessed grossly and analyzed by radiographic or histologic examination. RESULTS: Eight weeks after the implantation of the materials, substantial bone regeneration was observed at the calvarial defect restored with PRP incorporating the induced BMSCs. Less new bone formation was observed at the defect implanted with PRP incorporating the uninduced BMSCs. In contrast, no bone regeneration was detected at the defects implanted with the whole blood incorporating BMSCs, whether the BMSCs were induced or not. CONCLUSIONS: PRP can be used as a scaffold to carry in vitro expanded BMSCs to repair a rabbit's calvarial defect, but its inductive ability to BMSCs was limited. PMID- 22676825 TI - Sihler-stain study of buccal nerve distribution and its clinical implications. AB - OBJECTIVE: The aim of this study was to elucidate the precise distribution of the buccal nerve (BN) and its anatomic relationship with the infraorbital nerve (ION) and mental nerve (MN). STUDY DESIGN: Eight human specimens were subjected to Sihler staining, which is a highly accurate method for visualizing the distribution of nerve fibers without alteration of the nerve. RESULTS: It was found that the BN mainly proceeded medially from its point of entrance near the parotid duct opening to the angular area of mouth, giving off tiny branches along its trajectory. Some of these branches were distributed in upper angular area, over the cheilion, intermingling with branches of the ION. Intermingling of the BN and the MN was also observed in the premolar area of the lower lip. CONCLUSIONS: This new information regarding the distribution of BN should be taken into consideration when evaluating the possible effects of BN damage. PMID- 22676827 TI - Comparative study of hydroxyapatite from eggshells and synthetic hydroxyapatite for bone regeneration. AB - OBJECTIVES: The objective of this study was to evaluate the physical properties of synthetic hydroxyapatite (sHA) and hydroxyapatite from eggshells (eHA) by Fourier-transform infrared (FT-IR) and x-ray diffraction (XRD) and to compare the regenerative ability of the bone using sHA and eHA in a rabbit calvarial defect model. STUDY DESIGN: FT-IR and XRD were used to compare the physical properties of sHA and eHA. sHA was purchased from Sigma, and eHA was kindly donated from the Hungarian academy of science. Sixteen New Zealand white rabbits were used for the animal study. After the formation of a bilateral parietal bony defect (diameter 8.0 mm), either sHA or eHA was grafted into the defect. The defect in the control was left unfilled. Bone regeneration was evaluated by histomorphometry at 4 and 8 weeks after the operation. RESULTS: The peak broadening of the XRD experiments were in agreement with scanning electron microscope observation; the sHA had a smaller granule size than the eHA. The eHA had impurities phases of CaO (International Center for Diffraction Data (ICDD) 075-0264) and Ca(OH)(2) (ICDD 072-0156). Total new bone was 17.11 +/- 10.24% in the control group, 28.81 +/- 12.63% in sHA group, and 25.68 +/- 10.89% in eHA group at 4 weeks after the operation. The difference was not statistically significant (P > .05). Total new bone at 8 weeks after the operation was 27.50 +/- 10.89% in the control group, 38.62 +/- 17.42% in sHA group, and 41.99 +/- 8.44% in the eHA group. When comparing the sHA group to the control group, the difference was not statistically significant (P > .05). However, the eHA group was significantly different from the control group (P = .038). When comparing the eHA group to the sHA group, the difference was not statistically significant (P > .05). CONCLUSIONS: Both types of HA showed higher bone formation than the unfilled control. However, eHA had significantly higher bone formation than the unfilled control at 8 weeks after operation. PMID- 22676826 TI - Local treatment of chronic osteomyelitis with surgical debridement and tigecycline-impregnated calcium hydroxyapatite: an experimental study. AB - OBJECTIVE: The aim of this study was to determine the efficacy of tigecycline impregnated hydroxyapatite in the local treatment of chronic osteomyelitis experimentally induced in rat tibias with methicillin-resistant Staphylococcus aureus. STUDY DESIGN: Monocortical defects were established in the left tibias of 32 adult Wistar albino rats. Five rats were randomly selected and injected intramedullarly with saline solution (group 1), whereas chronic osteomyelitis was induced in other rats by intramedullary injection of S. aureus. Infected rats were then randomized and divided into 4 groups: group 2, no further treatment; group 3, debridement only; group 4, debridement followed by implantation of calcium hydroxyapatite; and group 5, debridement followed by implantation of tigecycline-impregnated calcium hydroxyapatite. On day 21 after induction, all rats in groups 2-5 showed signs of osteomyelitis. Rats in groups 1 and 2 were killed on day 21 after induction, whereas rats in groups 3, 4, and 5 underwent debridement surgery on day 21 after induction and were killed 21 days after debridement surgery. Tibias were analyzed histopathologically and cultured for S. aureus. RESULTS: Compared with group 2, histopathologic disease severity scores in groups 3, 4, and 5 were 37%, 44%, and 83% lower, respectively. Nontreated infected rats had the highest bacteria count (mean 5 * 10(5) colony-forming units/g bone), and bacterial count was 26%, 29%, and 79% lower in groups 3, 4, and 5, respectively, compared with group 2. CONCLUSIONS: Tigecycline-impregnated hydroxyapatite can have a potential in the treatment of chronic osteomyelitis of methicillin-resistant S. aureus origin, which may be considered as a therapeutic alternative by surgeons dealing with osteomyelitis. PMID- 22676828 TI - CAD/CAM and rapid prototyped titanium for reconstruction of ramus defect and condylar fracture caused by mandibular reduction. AB - Fracture or defect of the mandible is a serious complication of mandibular angleplasty, and precise reconstruction for such defect is still a huge challenge. This case report provides a new method based on CAD/CAM and rapid prototyped titanium for individual design, fabrication, and implantation of a mandibular ramus and angle. A 25-year-old woman with a square-shaped face, who had undergone mandibular outer cortex split ostectomy (MOCSO) 3 months earlier, was afflicted by a series of symptoms: asymmetric face, collapse of the right face, masticatory problems, deviation during mouth opening, malocclusion, and TMJ clicks. These symptoms were caused by unintentional removal of the fractured ramus during MOCSO. By means of CT scan data, rapid prototyping, reverse engineering, 3D display, and CAD/CAM, the individualized titanium implant was designed and fabricated. The 3D demo system of operative scheme demonstrated the operative procedure, and determined the position of the implant so as to obtain a perfect fit. Postoperatively, the patient regained satisfactory morphologic symmetry, facial appearance, occlusion, and TMJ functions. PMID- 22676829 TI - Localized mandibular enlargement in end-stage renal disease: two case reports and a review of the literature. AB - Enlargement of the jaws is an infrequently reported complication of chronic kidney disease mineral and bone disorder (CKD-MBD). Two cases of localized mandibular swellings in young patients with histories of end-stage renal disease are discussed with a review of the literature. Although 17 of the first 19 cases that were reported exhibited diffuse enlargement, these reports increase the number of localized swellings to 8 and support the contention that localized expansion of the jaws as a manifestation of CKD-MBD is more common than originally recognized. PMID- 22676830 TI - Unusually severe limitation of the jaw attributable to fibrodysplasia ossificans progressiva: a case report with cone-beam computed tomography findings. AB - Fibrodysplasia ossificans progressiva (FOP) is a rare hereditary connective tissue disease characterized by the progressive ectopic ossification of ligaments, tendons, and facial and skeletal muscles throughout life. Symptoms begin in childhood as localized soft tissue swellings. Immobility and articular dysfunction appear with involvement of the spine and proximal extremities. The temporomandibular joint (TMJ) is a critical component involved in the maxillofacial region, resulting in severe limitation of masticatory function, although TMJ involvement is rare. We report a case of FOP presenting as severely limited TMJ movements owing to ectopic calcification of the left coronoid process. In addition to the clinical examination, panoramic radiography and cone beam computed tomography images were obtained. The case is presented and the clinical and imaging findings, differential diagnosis, and treatment modalities are discussed. PMID- 22676831 TI - Unusual cone-beam computerized tomography presentation of traumatic (simple) bone cyst: case report and radiographic analysis. AB - Traumatic (simple) bone cyst (TBC) is an empty nonepithelial-lined cavity of the jaws. The majority of TBCs are located in the body or symphysis of the mandible. Clinically, the lesion is asymptomatic and often discovered incidentally on routine radiographic examination as a noncorticated sharply defined radiolucent area with undulating borders. Because tissues for histologic examination may be scant or nonexistent, the definite diagnosis is invariably achieved during surgery when the lesion is empty. In this report, we present a case of unusual bilateral synchronous TBCs of the mandible with possible traumatic etiology, featuring significant buccolingual expansion of the mandibular ramus and body, presence of septa, and probable displacement of the inferior alveolar canal. PMID- 22676832 TI - No plane is the best one-the volume is! PMID- 22676833 TI - Sunitinib related osteonecrosis of jaw: a case report. AB - A 58-year-old woman presented to the Oral and Maxillofacial Surgery Clinic experiencing severe limited mouth opening and exposed bone in the socket of the right mandibular third molar 8 months following the extraction of the tooth. The patient had been treated during the year before her presentation with sunitinib, an antiangiogenic drug, for renal cell carcinoma. The clinical, radiographic, and histologic picture of a chronic nonhealing extraction socket was consistent with osteonecrosis of the jaw (ONJ), although she had never been treated with bisphosphonates or corticosteroids. The treatment with sunitinib was discontinued and the patient was treated with antibiotics and physiotherapy for 12 weeks with complete recovery. Sunitinib may cause osteonecrosis of the jaw after oral surgical interventions with no previous exposure to bisphosphonates. The pathogenesis may be related to its antiangiogenic mechanism and impaired wound healing. Full recovery may require long-term cessation of the insulting drug combined with prolonged antibiotic treatment. PMID- 22676834 TI - A new submerged split-thickness skin graft technique to rebuild peri-implant keratinized soft tissue in composite flap reconstructed mandible or maxilla. AB - OBJECTIVE: The objective of this study was to introduce our preliminary experience on a submerged split-thickness skin graft (STSG) technique combined with secondary vestibuloplasty to rebuild keratinized peri-implant soft tissue and oral vestibule for patients with large oromandibular defects reconstructed by composite flaps. PATIENTS AND METHODS: Five patients were enrolled in this study. Stage 1 was submerged STSG and simultaneous implant placement. Stage 2 was the uncovering of the STSG and vestibuloplasty. The implant-borne fixed denture was inserted after this 2-stage treatment. All patients were followed for at least 12 months (average 18 months). RESULT: Eighteen implants were placed. The rebuilt peri-implant keratinized soft tissue was healthy clinically. The STSG graft had firm adherence to the underlying periosteum. The vestibule had adequate depth to maintain local hygiene. All implants were osseointegrated and all implant-borne prostheses were functioning well. CONCLUSION: Submerged STSG technique combined with secondary vestibuloplasty may become a feasible and effective solution to rebuild keratinized soft tissue before dental implant restoration. PMID- 22676835 TI - Walking on the edge: meanings of living in an ageing body and using a walker in everyday life - a phenomenological hermeneutic study. AB - BACKGROUND: In order to maintain one's state of health whilst growing older, the ability to walk is essential. AIM AND OBJECTIVE: The aim of this study was to illuminate the meanings of the lived experience of living in an ageing body and using a walker in daily life. METHODS: Narrative interviews were performed with seven older persons aged 79-95 years. The transcribed text was analysed using a phenomenological hermeneutic method. RESULTS: The key finding of the study was that the lived experience of living in an ageing body and using a walker in daily life was interpreted as 'walking on the edge' based on the themes 'Being vulnerable and dependent' and 'Being confident and independent'. CONCLUSIONS: The results highlight the importance of reflecting on this phenomenon as a health care professional while meeting the care needs of older persons who use walkers. IMPLICATIONS FOR PRACTICE: Nurses need to consider the walker as a personal and valued possession of the individual and handle the walker in agreement with the older person, placing the walker close at hand with the brakes locked to give secure support. PMID- 22676836 TI - Effect of display polarity and luminance contrast on visual lobe shape characteristics. AB - The effect of display polarity and luminance contrast on visual lobe (effective visual field) shape characteristics was studied using three levels of luminance contrast with combinations of positive and negative polarities. The binocular effective visual field for a detection task, with a peripherally presented target (V) embedded in a homogeneous competing background (Xs), was mapped on 24 imaginary axes passing through the fixation point. The results showed that visual lobes mapped using positive polarity were statistically larger in area, rounder and more regular in shape than those for negative polarity. The medium contrast condition lobes were more symmetric and regular than low contrast condition lobes, and lobe area and perimeter increased with increasing luminance contrast ratio. Under the interaction of positive polarity and high luminance contrast, visual lobes were found to be larger, smoother and rounder. The high level of luminance and contrast however resulted in a higher degree of visual discomfort. The results indicated that positive polarity and contrast of medium (26:1) to high (41:1) levels are possible display settings for better visual lobe characteristics and better anticipated search performance. Practitioner Summary: The effect of display polarity and luminance contrast on visual lobe shape characteristics was examined with uniform stimulus materials in this study. The results help to identify the optimum display settings for luminance contrast and display polarity to enhance lobe shape characteristics and hence search performance in industrial inspection tasks. PMID- 22676837 TI - Crosstalk between endoplasmic reticulum stress and oxidative stress in apoptosis induced by alpha-tocopheryl succinate in human gastric carcinoma cells. AB - alpha-Tocopheryl succinate (alpha-TOS) has been shown to be a potent apoptosis inducer and growth inhibitor in a variety of cancer cells. Our previous studies showed the important role of endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) generation in the apoptosis induced by alpha-TOS. However, the relationship of oxidative stress with ER stress is still controversial. The objective of the present study was to investigate the interplay between the two stress responses induced by alpha-TOS in SGC-7901 human gastric cancer cells. In response to alpha-TOS, cytological changes typical of apoptosis, induction of glucose-regulated protein 78 (GRP78) and CCAAT/enhancer-binding protein (C/EBP) homologous protein transcription factor (CHOP), and activation of caspase-4 were observed. And the antioxidant N-acetyl-l-cysteine inhibited induction of both GRP78 and CHOP by alpha-TOS transcriptionally and translationally. Furthermore, knocking down CHOP by RNA interference decreased ROS generation, increased glutathione level and induced glutathione peroxidase mRNA expression in alpha-TOS treated cells, whereas catalase and superoxide dismutases mRNA expression were not altered. The results imply that alpha-TOS induces ER stress response through ROS production, while CHOP perturbs the redox state of SGC-7901 cells treated with alpha-TOS. PMID- 22676838 TI - A network involving Rho-type GTPases, a paxillin and a formin homologue regulates spore length and spore wall integrity in the filamentous fungus Ashbya gossypii. AB - Fungi produce spores that allow for their dispersal and survival under harsh environmental conditions. These spores can have an astonishing variety of shapes and sizes. Using the highly polar, needle-shaped spores of the ascomycete Ashbya gossypii as a model, we demonstrated that spores produced by this organism are not simple continuous structures but rather consist of three different segments that correlate with the accumulation of different materials: a rigid tip segment, a more fragile main spore-compartment and a solid tail segment. Little is currently known about the regulatory mechanisms that control the formation of the characteristic spore morphologies. We tested a variety of mutant strains for their spore phenotypes, including spore size, shape and wall defects. The mutants that we identified as displaying such phenotypes are all known for their roles in the regulation of hyphal tip growth, including the formin protein AgBni1, the homologous Rho-type GTPases AgRho1a and AgRho1b and the scaffold protein AgPxl1. Our observations suggest that these proteins form a signalling network controlling spore length by regulating the formation of actin structures. PMID- 22676839 TI - Tobacco socialization and anti-tobacco ad effectiveness among children. AB - In order to prevent smoking onset among children, it is essential to know the process of smoking socialization and its various dimensions before being able to design any effective anti-tobacco advertisements. This research aims to conceptualize this process and to test the effectiveness of certain styles of anti-tobacco advertising addressed to children. The results show that both attitudinal and behavioral smoking socialization influence anti-tobacco advertisements effectiveness and that the least offensive and humoristic are most effective in Tunisia. PMID- 22676840 TI - Efficacy of an HIV testing campaign's messages for African American women. AB - We conducted a Web-based randomized controlled experiment to test the efficacy of the Take Charge. Take the Test. (TCTT) campaign messages. The experiment had two conditions: (a) exposure to campaign messages and (b) no exposure. Participants completed a baseline assessment, exposure condition participants were exposed to campaign materials for 2 weeks, and all participants completed a follow-up survey at 2- and 6-weeks postbaseline. Multivariate results indicate that exposure to TCTT messages was associated with increases in key knowledge items targeted by the campaign, intentions to get tested for HIV, and increases in peer-to-peer communication about getting an HIV test. PMID- 22676841 TI - Behavioral change communications on malaria prevention in Ghana. AB - The purpose of this study is to assess the various communications strategies designed to promote insecticide-treated nets (ITN) use among pregnant women and children. This study is an exploratory study into the communications activities by institutions involved in malaria prevention in Ghana. In-depth interviews were conducted and the data were analyzed. We found that most of the interventions are aimed at encouraging the target markets to acquire ITNs, although most messages on malaria prevention are not integrated. Several challenges were noted, including financial constraints, lack of human resources, cultural barriers, negative publicity, and negative perceptions on malaria. PMID- 22676842 TI - The impact of health-care service guarantees on consumer decision-making: an experimental investigation. AB - While examples of the successful use of service guarantees in health-care do exist, to-date, researchers have yet to examine this industry-specific application beyond a case study perspective. The results of this experiment begin to shed light on whether or not guarantees should be used, and if so, under what conditions are they appropriate. Respondents indicate that the thoughtful use of service guarantees can positively impact their perceptions of the health-care provider's reputation and, ultimately, their behavioral intentions towards the same provider. However, consideration must be given to the type of guarantee being offered and to whom the guarantee is targeted. PMID- 22676843 TI - Converging prescription brand shares as evidence of physician learning. AB - Within a drug category, there is an optimal brand the physician could choose to prescribe based on the patient's particular condition and characteristics. Physicians desire to prescribe the best brand for each patient for professional, moral, and legal reasons. Ideally, detailing provides information that supports this effort. This study finds that, over time, the proportion of prescriptions written for each brand moves toward a stable distribution--a convergence in which each brand's share in the category appears to match the proportion of prescription writing opportunities where the brand is the best choice for the patient. Detailing supports this convergence. PMID- 22676844 TI - Selective attention and the three-process memory model for the interpretation of verbal free recall in amyotrophic lateral sclerosis. AB - The present study investigates selective attention and verbal free recall in amyotrophic lateral sclerosis (ALS) and examines the contribution of selective attention, encoding, consolidation, and retrieval memory processes to patients' verbal free recall. We examined 22 non-demented patients with sporadic ALS and 22 demographically related controls using Stroop Neuropsychological Screening Test (SNST; selective attention) and Rey Auditory Verbal Learning Test (RAVLT; immediate & delayed verbal free recall). The item-specific deficit approach (ISDA) was applied to RAVLT to evaluate encoding, consolidation, and retrieval difficulties. ALS patients performed worse than controls on SNST (p < .001) and RAVLT immediate and delayed recall (p < .001) and showed deficient encoding (p = .001) and consolidation (p = .002) but not retrieval (p = .405). Hierarchical regression analysis revealed that SNST and ISDA indices accounted for: (a) 91.1% of the variance in RAVLT immediate recall, with encoding (p = .016), consolidation (p < .001), and retrieval (p = .032) significantly contributing to the overall model and the SNST alone accounting for 41.6%; and (b) 85.2% of the variance in RAVLT delayed recall, with consolidation (p < .001) and retrieval (p = .008) significantly contributing to the overall model and the SNST alone accounting for 39.8%. Thus, selective attention, encoding, and consolidation, and to a lesser extent of retrieval, influenced both immediate and delayed verbal free recall. Concluding, selective attention and the memory processes of encoding, consolidation, and retrieval should be considered while interpreting patients' impaired free recall. (JINS, 2012, 18, 1-10). PMID- 22676845 TI - Influence of 50 Hz-1 mT magnetic field on human median nerve. AB - In this study, human median nerve was exposed to power frequency magnetic fields in order to provide clarification for possibly changeable nerve conduction mechanism. The nerve was exposed to 50 Hz magnetic field by utilizing a special Helmholtz applicator. The experiments were carried out with six healthy human volunteers. Median motor distal amplitude/proximal amplitude ratios were recorded from adult human median nerve pre-exposure, during, and post-exposure to a 50 Hz, 1 mT magnetic field. The result of 18 measurements shows that median motor distal amplitude/proximal amplitude ratio significantly decreases in pre-exposure state as compare to post exposure of which. The results of this study may be useful for some nerve rehabilitation, excitation, and stimulation in more effective/safe physical therapy. Additionally, 50 Hz, 1 mT sinusoidal magnetic field should not be recognizing as safe for conduction mechanism on a nerve. These mechanisms would be cleared by new advanced engineering models in other future works. PMID- 22676846 TI - Transport of Bacillus thuringiensis var. kurstaki from an outdoor release into buildings: pathways of infiltration and a rapid method to identify contaminated buildings. AB - Understanding the fate and transport of biological agents into buildings will be critical to recovery and restoration efforts after a biological attack in an urban area. As part of the Interagency Biological Restoration Demonstration (IBRD), experiments were conducted in Fairfax County, VA, to study whether a biological agent can be expected to infiltrate into buildings following a wide area release. Bacillus thuringiensis var. kurstaki is a common organic pesticide that has been sprayed in Fairfax County for a number of years to control the gypsy moth. Because the bacterium shares many physical and biological properties with Bacillus anthracis, the results from these studies can be extrapolated to a bioterrorist release. In 2009, samples were collected from inside buildings located immediately adjacent to a spray block. A combined probabilistic and targeted sampling strategy and modeling were conducted to provide insight into likely methods of infiltration. Both the simulations and the experimental results indicate sampling entryways and heating, ventilation, and air conditioning (HVAC) filters are reasonable methods for "ruling in" a building as contaminated. Following a biological attack, this method is likely to provide significant savings in time and labor compared to more rigorous, statistically based characterization. However, this method should never be used to "rule out," or clear, a building. PMID- 22676847 TI - Immunoregulatory T cells in multiple sclerosis and the effect of interferon beta and glatiramer acetate treatment on T cell subpopulations. AB - INTRODUCTION: Multiple sclerosis (MS) is a chronic disease characterized by demyelination and chronic inflammation of the central nervous system (CNS). Many of the immune cells including T and B cells seem to be involved in disease pathogenesis by inducing or controlling the immune responses in the nervous system of MS patients. The objective of this study was to evaluate the differences in subpopulations of T cells between MS patients and healthy controls and the effects of interferon beta (INF-beta) and glatiramer acetate (GA) treatment on T cell subpopulations. MATERIAL AND METHODS: We have investigated the frequency of subpopulations of T cells using flow cytometry in 84 relapsing remitting MS patients; forty-five patients started treatment with INF-beta and eighteen patients with GA, twenty-one patients were not treated. We collected blood samples at the beginning and after 6 and 12 months. RESULTS: We observed a significant decrease in CD4(+)CD25(+) Treg cells (p=0.03) and a significant increase in T helper cells (p=0.002) and central memory T cells (p=0.03) in MS patients compared to healthy controls. After INF-beta therapy, we demonstrated a significant increase in naive T cells (p=0.008), a decline in central memory T cells (p=0.01). After GA therapy, we observed a significant increase in naive T cells (p=0.04), a decrease in central memory T cells (p=0.03) and an increase in T-suppressor cells (p=0.008). CONCLUSION: In conclusion, we demonstrated the imbalance of T-cell subpopulations in MS patients and the potential benefit of DMD (disease modifying drugs) treatment on its restoration. PMID- 22676848 TI - Se-Jin Lee, myostatin discoverer, elected to the National Academy of Science. AB - Se-Jin Lee was elected member to the National Academy of Sciences on 28 April 2012. Dr Lee is responsible for the discovery of myostatin, a critical regulator of skeletal muscle mass and function. He also determined the primary binding receptor for myostatin, and has characterized additional transforming growth factor-beta family members acting in this pathway. PMID- 22676850 TI - Determination of clinical and demographic predictors of laboratory-confirmed influenza with subtype analysis. AB - BACKGROUND: Rapid influenza diagnosis is important for early identification of outbreaks, effective management of high-risk contacts, appropriate antiviral use, decreased inappropriate antibiotic use and avoidance of unnecessary laboratory testing. Given the inconsistent performance of many rapid influenza tests, clinical diagnosis remains integral for optimizing influenza management. However, reliable clinical diagnostic methods are not well-established. This study assesses predictors of influenza, and its various subtypes, in a broad population at the point of care, across age groups, then evaluates the performance of clinical case definitions composed of identified predictors. METHODS: Respiratory specimens and demographic and clinical data were obtained from 3- to 80-year-old US military family members presenting for care with influenza-like illness (ILI) from November 2007 to April 2008. Molecular and virus isolation techniques were used to detect and subtype influenza viruses. Associations between influenza diagnosis and demographic/clinical parameters were assessed by logistic regression, including influenza type and subtype analyses. The predictive values of multiple combinations of identified clinical predictors (case definitions), and the Centers for Disease Control and Prevention (CDC) ILI case definition, were estimated. RESULTS: Of 789 subjects, 220 (28%) had laboratory-confirmed influenza (51 A(H1), 46 A(H3), 19 A(unsubtypeable), 67 B, 1 AB coinfection), with the proportion of influenza A to B cases highest among 6- to 17-year-olds (p = 0.019). Independent predictors of influenza included fever, cough, acute onset, body aches, and vaccination status among 6- to 49-year-olds, only vaccination among 3- to 5-year-olds, and only fever among 50- to 80-year-olds. Among 6- to 49 year-olds, some clinical case definitions were highly sensitive (100.0%) or specific (98.6%), but none had both parameters over 60%, though many performed better than the CDC ILI case definition (sensitivity 37.7%, 95% confidence interval 33.6-41.9% in total study population). CONCLUSIONS: Patterns of influenza predictors differed across age groups, with most predictors identified among 6- to 49-year-olds. No combination of clinical and demographic predictors served as a reliable diagnostic case definition in the population and influenza season studied. A standardized clinical case definition combined with a point-of care laboratory test may be the optimal rapid diagnostic strategy available. PMID- 22676849 TI - Reduced osteoblast activity in the mice lacking TR4 nuclear receptor leads to osteoporosis. AB - BACKGROUND: Early studies suggested that TR4 nuclear receptor might play important roles in the skeletal development, yet its detailed mechanism remains unclear. METHODS: We generated TR4 knockout mice and compared skeletal development with their wild type littermates. Primary bone marrow cells were cultured and we assayed bone differentiation by alkaline phosphatase and alizarin red staining. Primary calvaria were cultured and osteoblastic marker genes were detected by quantitative PCR. Luciferase reporter assays, chromatin immunoprecipitation (ChIP) assays, and electrophoretic mobility shift assays (EMSA) were performed to demonstrate TR4 can directly regulate bone differentiation marker osteocalcin. RESULTS: We first found mice lacking TR4 might develop osteoporosis. We then found that osteoblast progenitor cells isolated from bone marrow of TR4 knockout mice displayed reduced osteoblast differentiation capacity and calcification. Osteoblast primary cultures from TR4 knockout mice calvaria also showed higher proliferation rates indicating lower osteoblast differentiation ability in mice after loss of TR4. Mechanism dissection found the expression of osteoblast markers genes, such as ALP, type I collagen alpha 1, osteocalcin, PTH, and PTHR was dramatically reduced in osteoblasts from TR4 knockout mice as compared to those from TR4 wild type mice. In vitro cell line studies with luciferase reporter assay, ChIP assay, and EMSA further demonstrated TR4 could bind directly to the promoter region of osteocalcin gene and induce its gene expression at the transcriptional level in a dose dependent manner. CONCLUSIONS: Together, these results demonstrate TR4 may function as a novel transcriptional factor to play pathophysiological roles in maintaining normal osteoblast activity during the bone development and remodeling, and disruption of TR4 function may result in multiple skeletal abnormalities. PMID- 22676852 TI - UBQLN2 in familial amyotrophic lateral sclerosis in The Netherlands. AB - Recently it was discovered that mutations in the UBQLN2 gene were a cause of an X linked dominant type of familial amyotrophic lateral sclerosis (ALS). We investigated the frequency of mutations in this gene in a cohort of 92 families with ALS in the Netherlands. Eight families were excluded because of male-to-male transmission. In the remaining 84 familial ALS cases no mutations were discovered in UBQLN2. Hence, UBQLN2 was not found to be a cause of familial ALS in the Netherlands. PMID- 22676851 TI - A CD11d monoclonal antibody treatment reduces tissue injury and improves neurological outcome after fluid percussion brain injury in rats. AB - Traumatic brain injury (TBI) is an international health concern often resulting in chronic neurological abnormalities, including cognitive deficits, emotional disturbances, and motor impairments. An anti-CD11d monoclonal antibody that blocks the CD11d/CD18 integrin and vascular cell adhesion molecule (VCAM)-1 interaction following experimental spinal cord injury improves functional recovery, while reducing the intraspinal number of neutrophils and macrophages, oxidative activity, and tissue damage. Since the mechanisms of secondary injury in the brain and spinal cord are similar, we designed a study to evaluate fully the effects of anti-CD11d treatment after a moderate lateral fluid percussion TBI in the rat. Rats were treated at 2 h after TBI with either the anti-CD11d antibody or an isotype-matched control antibody 1B7, and both short (24- to 72-h) and long (4-week) recovery periods were examined. The anti-CD11d integrin treatment reduced neutrophil and macrophage levels in the injured brain, with concomitant reductions in lipid peroxidation, astrocyte activation, amyloid precursor protein accumulation, and neuronal loss. The reduced neuroinflammation seen in anti-CD11d-treated rats correlated with improved performance on a number of behavioral tests. At 24 h, the anti-CD11d group performed significantly better than the 1B7 controls on several water maze measures of spatial cognition. At 4 weeks post-injury the anti-CD11d-treated rats had better sensorimotor function as assessed by the beam task, and reduced anxiety-like behaviors, as evidenced by elevated-plus maze testing, compared to 1B7 controls. These findings suggest that neuroinflammation is associated with behavioral deficits after TBI, and that anti CD11d antibody treatment is a viable strategy to improve neurological outcomes after TBI. PMID- 22676854 TI - Catalyst- and solvent-free click synthesis of cyclodextrin-based polyrotaxanes exploiting a nitrile N-oxide. AB - A catalyst- and solvent-free synthesis of cyclodextrin-based polyrotaxanes exploiting a stable nitrile N-oxide as an end-capping agent was achieved. The C-C bond-forming end-capping reaction of an allyl-terminated pseudopolyrotaxane with the nitrile N-oxide proceeded smoothly by solid-state grinding in a mortar to afford a polyrotaxane. PMID- 22676853 TI - Calcium phosphatase calcineurin influences tau metabolism. AB - Alzheimer's disease (AD) is characterized by neuronal loss and the accumulation of beta-amyloid plaques and neurofibrillary tangles in the brain. Cerebrospinal fluid (CSF) levels of beta-amyloid and tau/phospho-tau 181 (ptau 181) are also associated with AD. We have previously demonstrated that a single nucleotide polymorphism in calcineurin is associated with CSF ptau 181 levels and AD progression. In this study, we demonstrate that calcineurin protein levels are inversely correlated with dementia severity and Braak tangle stage in AD brains, and calcineurin activity is globally reduced in AD brains. We then sought to model the observed changes in CSF tau by measuring extracellular tau in cultured cells. SH-SY5Y cells treated with calcineurin inhibitors produced reduced calcineurin activity and a corresponding increase in extracellular ptau 181. These findings are consistent with our observations in AD patients, who have elevated CSF ptau 181 and reduced calcineurin activity in brain extracts. Thus, we have identified a gene that contributes to AD pathology and has functional consequences on tau metabolism in cultured cells. PMID- 22676855 TI - Flow cytometric analysis of somaclonal variation in lineages of Hosta sports detects polyploidy and aneuploidy chimeras. AB - Somaclonal variation of some 124 specially selected cultivars of Hosta Tratt. (Hostaceae) was investigated. Nuclear DNA contents (2C-value) were measured by flow cytometry of leaves and roots of L1, L2 and L3 layers derived from apical meristems. These values were then converted to inferred ploidies by comparing the measured 2C-values and ploidy with those of the parent plant. During tissue culture propagation, on occasion diploid (L1-L2-L3 = 2-2-2) hostas give rise to polyploids, such as fully tetraploids (4-4-4), and periclinal chimeras, such as partial tetraploids (4-2-2). Continual propagation can result in partial tetraploids becoming full tetraploids. Nuclear DNA of some diploids increased with incomplete chromosome sets resulting in fully aneuploids, such as hostas with a DNA ploidy of L1-L2-L3 = 2.5-2.5-2.5 and 3.7-3.7-3.7, and even in aneuploid periclinal chimeras, such as L1-L2-L3 = 2.5-2-2 and 3.8-2-2. The polyploidy of L1, irrespective of the ploidy of L2 and L3, is found to mainly determine the thickness of leaves. Also the higher the ploidy of L1, the wider and more intense in color is the leaf margin. The measurements of Hosta cultivars and their lineages of sports show that chromosome losses or gains are an important source of new cultivars. The complexity of chromosomal distribution in lineages of several Hosta cultivars is discussed. PMID- 22676857 TI - Pregnancy-associated breast cancer and increased risk of pregnancy-associated recurrence: a case report. AB - INTRODUCTION: Pregnancy-associated breast cancer refers to breast cancer diagnosed during pregnancy, lactation, or within twelve months postpartum. Recent studies suggest that, when matched for age and stage, the prognosis of pregnancy associated breast cancer is comparable to non-pregnancy-associated breast cancer. However, the risk for breast cancer recurrence associated with subsequent pregnancies in this population is not clear. CASE PRESENTATION: We describe the case of a Caucasian woman who was initially treated for pregnancy-associated breast cancer at age 23, three months after the birth of her third child. She underwent a total mastectomy with axillary node dissection, followed by chemotherapy and hormonal therapy. Ten years later, when the patient was 24 weeks pregnant with her fourth child, she presented with an ipsilateral chest wall recurrence of breast cancer. To the best of our knowledge, this represents the first reported case of a pregnancy-associated recurrence in a patient previously treated for pregnancy-associated breast cancer. CONCLUSION: The case described here is the first report of a second occurrence of pregnancy-associated breast cancer. This case raises the possibility that pregnancy may represent a unique trigger for breast malignancy in a specific cohort of women. Although there is data showing no increase in the risk of recurrence for women who become pregnant after breast cancer treatment, pregnancy-associated breast cancer may be a distinct clinical category where subsequent pregnancies after treatment may confer an increased risk of recurrent disease. PMID- 22676856 TI - Randomized controlled double-blind trial of optimal dose methylphenidate in children and adolescents with severe attention deficit hyperactivity disorder and intellectual disability. AB - BACKGROUND: Attention deficit hyperactivity disorder is increased in children with intellectual disability. Previous research has suggested stimulants are less effective than in typically developing children but no studies have titrated medication for individual optimal dosing or tested the effects for longer than 4 weeks. METHOD: One hundred and twenty two drug-free children aged 7-15 with hyperkinetic disorder and IQ 30-69 were recruited to a double-blind, placebo controlled trial that randomized participants using minimization by probability, stratified by referral source and IQ level in a one to one ratio. Methylphenidate was compared with placebo. Dose titration comprised at least 1 week each of low (0.5 mg/kg/day), medium (1.0 mg/kg/day) and high dose (1.5 mg/kg/day). Parent and teacher Attention deficit hyperactivity disorder (ADHD) index of the Conners Rating Scale-Short Version at 16 weeks provided the primary outcome measures. Clinical response was determined with the Clinical Global Impressions scale (CGI I). Adverse effects were evaluated by a parent-rated questionnaire, weight, pulse and blood pressure. Analyses were by intention to treat. TRIAL REGISTRATION: ISRCTN 68384912. RESULTS: Methylphenidate was superior to placebo with effect sizes of 0.39 [95% confidence intervals (CIs) 0.09, 0.70] and 0.52 (95% CIs 0.23, 0.82) for the parent and teacher Conners ADHD index. Four (7%) children on placebo versus 24 (40%) of those on methylphenidate were judged improved or much improved on the CGI. IQ and autistic symptoms did not affect treatment efficacy. Active medication was associated with sleep difficulty, loss of appetite and weight loss but there were no significant differences in pulse or blood pressure. CONCLUSIONS: Optimal dosing of methylphenidate is practical and effective in some children with hyperkinetic disorder and intellectual disability. Adverse effects typical of methylphenidate were seen and medication use may require close monitoring in this vulnerable group. PMID- 22676858 TI - Air embolism during operative hysteroscopy: TEE-guided resuscitation. AB - During hysteroscopic surgery there are concerns about potential complications such as venous air and gas embolism. The incidence of subclinical air emboli events during operative hysteroscopy is significantly underestimated. The manifestations of this complication may range from an unnoticeable decrease in P(ET)CO(2) to the need for resuscitation. Three cases of air embolism with variable outcomes occurring during general anesthesia for operative hysteroscopy in otherwise healthy patients are presented. PMID- 22676859 TI - Transient ischaemic attack (TIA) knowledge in general practice: a cross-sectional study of Western Adelaide general practitioners. AB - BACKGROUND: With evidence to support early assessment and management of TIAs, the role of the general practitioner (GP) needs to be considered in developing a TIA service in Western Adelaide. We thus aimed to determine GP knowledge of TIA assessment and management and identify perceived barriers, in order to tailor subsequent GP education and engage primary care in the co-ordinated care of TIA patients. FINDINGS: A self-administered questionnaire was mailed to all GPs (n = 202) in the Adelaide Western General Practice Network. Response frequencies were calculated for all variables, and associations examined by univariate analysis.32 GPs responded. All respondents correctly identified early risk of stroke following a TIA. Difficulty accessing neurological expertise was identified as a barrier (40.6 %), as was a lack of GP knowledge (18.8 %). Areas for improvement included access to neurologists (36.7 %), relevant guidelines and education (43.3 %). CONCLUSIONS: Diagnosis of TIA is difficult and this study highlights the need for further education and practical guidelines for GPs. With this training, GPs could be better equipped to assess and manage TIAs effectively in the community in consultation with stroke physicians. PMID- 22676860 TI - Integration of maternal genome into the neonate genome through breast milk mRNA transcripts and reverse transcriptase. AB - Human milk samples contain microvesicles similar to the retroviruses. These microvesicles contain mRNA transcripts and possess reverse transcriptase activity. They contain about 14,000 transcripts representing the milk transcriptome. Microvesicles are also enriched with proteins related to "caveolar mediated endocytosis signaling" pathway. It has recently been reported that microvesicles could be transferred to other cells by endocytosis and their RNA content can be translated and be functional in their new location. A significant percentage of the mammalian genome appears to be the product of reverse transcription, containing sequences whose characteristics point to RNA as a template precursor. These are mobile elements that move by way of transposition and are called retrotransposons. We thought that retrotransposons may stem from about 14,000 transcriptome of breast milk microvesicles, and reviewed the literature.The enhanced acceptance of maternal allografts in children who were breast-fed and tolerance to the maternal MHC antigens after breastfeeding may stem from RNAs of the breast milk microvesicles that can be taken up by the breastfed infant and receiving maternal genomic information. We conclude that milk microvesicles may transfer genetic signals from mother to neonate during breastfeeding. Moreover, transfer of wild type RNA from a healthy wet-nurse to the suckling neonate through the milk microvesicles and its subsequent reverse transcription and integration into the neonate genome could result in permanent correction of the clinical manifestations in genetic diseases. PMID- 22676861 TI - Diagnostic and therapeutic challenges in a liver transplant recipient with central nervous system invasive aspergillosis. AB - This is a case report of central nervous system (CNS) invasive aspergillosis (IA) in a liver transplant recipient, which illustrates the utility of enzyme-based diagnostic tools for the timely and accurate diagnosis of IA, the treatment challenges and poor outcomes associated with CNS IA in liver transplant recipients. PMID- 22676862 TI - Testosterone up. A case of disease mongering? PMID- 22676863 TI - Disciplinary notations on the Australian Register of Medical Practitioners [corrected]. PMID- 22676867 TI - Not window dressing, but key to making medical research matter. PMID- 22676864 TI - Is the end of chronic hepatitis C virus infection in sight? PMID- 22676869 TI - Tempering hope with realism: induced pluripotent stem cells in regenerative medicine. PMID- 22676868 TI - Disease mongering and low testosterone in men: the tale of two regulatory failures. PMID- 22676870 TI - Inappropriate defibrillator shocks caused by oversensing of T-wave in hyperkalaemia. PMID- 22676871 TI - Targeted primary care-based mental health services for young Australians. PMID- 22676872 TI - Targeted primary care-based mental health services for young Australians. PMID- 22676873 TI - Targeted primary care-based mental health services for young Australians. Comment. PMID- 22676874 TI - The MJA and Gawler: a case of self-censorship? PMID- 22676875 TI - The MJA and Gawler: a case of self-censorship? Comment. PMID- 22676877 TI - The changing therapeutic landscape for hepatitis C. AB - The next decade will be a crucial period in the public health response to hepatitis C virus (HCV) infection. The rapid development of direct-acting antiviral therapy for HCV infection has brought considerable optimism to the HCV sector, with the realistic hope that therapeutic intervention will soon be more effective and offer shorter treatment duration. The initial phase of combination pegylated interferon, ribavirin and a protease inhibitor will be associated with increased toxicity and complexity of therapeutic management but, over the course of the decade, strategies including interferon-free combination direct-acting antiviral regimens with enhanced tolerability and simplified dosing schedules and monitoring protocols will emerge. PMID- 22676878 TI - Hepatitis C treatment outcomes in Australian clinics. AB - OBJECTIVE: To determine hepatitis C (HCV) treatment effectiveness and predictors of response in the "real-world" Australian clinic setting. DESIGN, SETTING AND PARTICIPANTS: Patients with chronic HCV, who were HCV-treatment-naive at enrolment, and were then treated with standard therapy (pegylated interferon alpha plus ribavirin), were recruited prospectively through a national network of 24 HCV clinics between April 2008 and December 2009. Patients were interviewed and a medical record review was conducted at enrolment and at routine follow-up clinic visits. MAIN OUTCOME MEASURES: Proportion of patients achieving a sustained virological response (SVR), predictors of SVR, and impact of treatment on biochemical markers of liver disease (alanine aminotransferase levels and aspartate aminotransferase-to-platelet ratio index scores). RESULTS: The SVR by intention to treat was 60% (327/550). Infection with HCV genotype 2 or 3 (compared with genotype 1) was an independent predictor of SVR (odds ratio [OR], 2.45; 95% CI, 1.70-3.52), while HIV coinfection (OR, 0.28; 95% CI, 0.10-0.82), cirrhosis (OR, 0.38; 95% CI, 0.18-0.81), and increased body mass index for >= 30 kg/m(2) v <= 25 kg/m(2) (OR, 0.58; 95% CI, 0.35-0.96) were independently associated with lower SVR. There was a significant improvement in biochemical markers of liver disease following SVR (P< 0.001). CONCLUSIONS: Our findings are similar to those seen in clinical trials, despite the inclusion of patients with a broad range of comorbid conditions such as injecting drug and alcohol use and psychiatric illness. They suggest that, with appropriate patient and infrastructure support, expansion of treatment services to the broader HCV infected community is warranted. PMID- 22676880 TI - Pharmacoepidemiology of testosterone prescribing in Australia, 1992-2010. AB - OBJECTIVE: To describe patterns of testosterone prescribing in Australia over the past two decades by state or territory and by product type. DESIGN AND SETTING: Observational analysis of testosterone prescribing data obtained from two independent data sources--the Pharmaceutical Benefits Scheme (PBS) and IMS, a source of commercial pharmaceutical sales data. MAIN OUTCOME MEASURES: Temporal trends in testosterone prescribing--measured as units prescribed (converted into monthly defined doses) and expenditure--to state or territory and product type (injectable, implantable, transdermal and oral). RESULTS: Over two decades, total annual expenditure on testosterone products increased ninefold to $12.7 million according to PBS data and fivefold to $16.3 million according to IMS data. When adjusted for inflation and population growth, expenditure increased 4.5-fold according to PBS data and 2.5-fold according to IMS data. The patterns of testosterone prescribing according to PBS and IMS data were highly congruent. When converted into monthly defined dose units, testosterone prescribing increased over the two decades with approximately twofold differences in total testosterone prescribed per capita between the states and territories with the highest and lowest rates of prescribing. When analysed by product type, the stable market patterns over the first 15 years were disrupted by sharp changes to create market dominance owing to introduction of two new testosterone products--a depot injectable testosterone and a transdermal testosterone gel. CONCLUSIONS: The progressive increase in PBS-subsidised testosterone prescribing without changes in proven medical indications or improvements in diagnosis of pathologically based androgen deficiency are likely to be due to promotion-driven non-compliance with PBS prescribing criteria, indicating that more effective implementation of the criteria is needed. PMID- 22676879 TI - Modelling antiviral treatment to prevent hepatitis C infection among people who inject drugs in Victoria, Australia. AB - OBJECTIVES: To develop a mathematical model to project the potential impact of hepatitis C virus (HCV) treatment on HCV infection prevalence among people who inject drugs (PWID). DESIGN AND SETTING: An existing model of HCV transmission among PWID was parameterised using data from Victoria, Australia, including specific parameter estimates of the number of people who are currently active injecting drug users, average duration of injecting, chronic HCV infection prevalence among PWID, annual mortality, and annual HCV treatment rate. We also explored the impact of prevalence uncertainty, program scale-up, and new treatments. MAIN OUTCOME MEASURE: Prevalence of chronic HCV infection among people who are currently active injecting drug users. RESULTS: With annual treatment rates of 13, 17, or 25 per 1000 PWID, the model predicts relative prevalence reductions of 20%, 30%, and 50%, respectively, within 30 years. If new treatments giving higher sustained viral response rates are available in 5 years, estimated impact is increased by 21%-23% at 15 years, and 17%-38% at 30 years, depending on treatment rates. CONCLUSIONS: This model suggests that modest rates of current HCV treatment among PWID in Victoria, Australia could halve HCV infection prevalence among PWID in 30 years. This finding suggests that interventions aimed at increasing access to HCV treatment in community clinics will benefit individual PWID and reduce HCV infection prevalence. PMID- 22676881 TI - Shared care for chronic eye diseases: perspectives of ophthalmologists, optometrists and patients. AB - OBJECTIVE: To report the perspectives of optometrists, ophthalmologists and patients on a model of shared care for patients with chronic eye diseases. DESIGN, SETTING AND PARTICIPANTS: Qualitative study of a model of shared care between optometrists and ophthalmologists for patients with stable age-related macular degeneration, diabetic retinopathy and glaucoma, trialled by the Royal Victorian Eye and Ear Hospital in Melbourne during 2007-2009. Semi-structured interviews were conducted with optometrists, ophthalmologists and patients at completion of the project to obtain their perspectives on this model. RESULTS: Seventeen optometrists submitted expressions of interest to participate, and 12 completed web-based training modules and clinical observerships and adhered to specified examination and reporting protocols. All five participating ophthalmologists and 11 of the optometrists were interviewed. Ninety-eight patients participated and 37 were interviewed. Optometrists not only met ophthalmologists' expectations but exceeded them, appropriately detecting and referring patients with additional, previously undetected conditions. Patients reported savings in travel time and were satisfied with the quality of care they received. Optometrists, ophthalmologists and patients indicated a general acceptance of shared care arrangements, although there were some issues relating to interprofessional trust. CONCLUSIONS: Shared care between local optometrists and hospital-based ophthalmologists can help to reduce patient waiting time for review and offers an opportunity for these two groups of eye care professionals to collaborate in providing localised care for the benefit of patients. However, trust and relationship building need to be further developed. PMID- 22676882 TI - Two cases of asymptomatic HBV "vaccine breakthrough" infection detected in blood donors screened for HBV DNA. PMID- 22676883 TI - Medical schools as agents of change: socially accountable medical education. AB - Medical education reform can make an important contribution to the future health care of populations. Social accountability in medical education was defined by the World Health Organization in 1995, and an international movement for change is gathering momentum. While change can be enabled with policy levers, such as funding tied to achieving equity outcomes and systems of accreditation, medical schools and students themselves can lead the transformation agenda. An international movement for change and coalitions of medical schools with an interest in socially accountable medical education provide a "community of practice" that can drive change from within. PMID- 22676884 TI - Ward 5E Bed 12. PMID- 22676886 TI - Margaret Buckingham, discoveries in skeletal and cardiac muscle development, elected to the National Academy of Science. AB - Margaret Buckingham was presented as a newly elected member to the National Academy of Sciences on 28 April 2012. Over the course of her career, Dr Buckingham made many seminal contributions to the understanding of skeletal muscle and cardiac development. Her studies on cardiac progenitor populations has provided insight into understanding heart malformations, while her work on skeletal muscle progenitors has elucidated their embryonic origins and the transcriptional hierarchies controlling their developmental progression. PMID- 22676885 TI - A review of the potential mechanisms for the lowering of colorectal oncogenesis by butyrate. AB - Colorectal cancer (CRC) is a leading cause of preventable cancer deaths worldwide, with dietary factors being recognised as key risk modifiers. Foods containing dietary fibre are protective to a degree that the World Cancer Research Fund classifies the evidence supporting their consumption as 'convincing'. The mechanisms by which fibre components protect against CRC remain poorly understood, especially their interactions with the gut microbiome. Fibre is a composite of indigestible plant polysaccharides and it is emerging that fermentable fibres, including resistant starch (RS), are particularly important. RS fermentation induces SCFA production, in particular, relatively high butyrate levels, and in vitro studies have shown that this acid has strong anti tumorigenic properties. Butyrate inhibits proliferation and induces apoptosis of CRC cell lines at physiological concentrations. These effects are attributed to butyrate's ability to alter gene transcription by inhibiting histone deacetylase activity. However, the more recent discovery of G-protein coupled receptors that bind butyrate and other SCFA and data obtained from proteomic and genomic experiments suggest that alternative pathways are involved. Here, we review the mechanisms involved in butyrate-induced apoptosis in CRC cells and, additionally, the potential role this SCFA may play in mediating key processes in tumorigenesis including genomic instability, inflammation and cell energy metabolism. This discussion may help to inform the development of strategies to lower CRC risk at the individual and population levels. PMID- 22676887 TI - Inhibition of pentylenetetrazole-induced seizure in mice by using a 4 Hz magnetic field: a comparative study with a 60 Hz magnetic field. AB - We investigated the comparative effects of 4 and 60 Hz magnetic fields on pentylenetetrazole (PTZ)-induced seizure in mice. For this study, we measured the latent time to seizure, seizure duration, and lethality induced by PTZ in mice exposed to 4 and 60 Hz magnetic fields (MF) for 30 min. Compared to sham-exposed controls, the latent time to tail twitching and seizure in the 4 Hz MF group was significantly decreased while the latent time to seizure in the 60 Hz MF group was significantly increased. The seizure duration in the 4 Hz MF group was significantly decreased while that in the 60 Hz MF group was significantly increased. More importantly, while the mice exposed to a 60 Hz MF experienced significantly increased lethality after seizure convulsion, those exposed to a 4 Hz MF showed no lethality, with a shortening of the duration of seizure. This beneficial effect of a 4 Hz MF on seizure has the same implication as the anti oxidative effects of a 4 Hz MF observed in our previous work. The results of our current and previous works indicate that a 4 Hz MF may be used as a therapeutic physical agent for the treatment of oxidative stress-induced diseases, including seizure, with or without chemical drugs. PMID- 22676888 TI - Involvement of mitogen-activated protein kinase pathways in expression of the water channel protein aquaporin-4 after ischemia in rat cortical astrocytes. AB - Brain edema after ischemic brain injury is a key determinant of morbidity and mortality. Aquaporin-4 (AQP4) plays an important role in water transport in the central nervous system and is highly expressed in brain astrocytes. However, the AQP4 regulatory mechanisms are poorly understood. In this study, we investigated whether mitogen-activated protein kinases (MAPKs), which are involved in changes in osmolality, might mediate AQP4 expression in models of rat cortical astrocytes after ischemia. Increased levels of AQP4 in primary cultured astrocytes subjected to oxygen-glucose deprivation (OGD) and 2 h of reoxygenation were observed, after which they immediately decreased at 0 h of reoxygenation. Astrocytes exposed to OGD injury had significantly increased phosphorylation of three kinds of MAPKs. Treatment with SB203580, a selective p38 MAPK inhibitor, or SP600125, a selective c-Jun N-terminal kinase inhibitor, significantly attenuated the return of AQP4 to its normal level, and SB203580, but not SP600125, significantly decreased cell death. In an in vivo study, AQP4 expression was upregulated 1-3 days after reperfusion, which was consistent with the time course of p38 phosphorylation and activation, and decreased by the p38 inhibition after transient middle cerebral artery occlusion (MCAO). These results suggest that p38 MAPK may regulate AQP4 expression in cortical astrocytes after ischemic injury. PMID- 22676889 TI - The influence of inhibitory control and episodic memory on the risky sexual behavior of young adult cannabis users. AB - Cannabis use is associated with risky sexual behavior (RSB) and sex-related negative health consequences. This investigation examined the role of inhibitory control and episodic memory in predicting RSB and sex-related negative consequences among current cannabis users. Findings indicated that the relationships among cannabis, neurocognition, and sexual-risk varied according to the dimension of neurocognition and the parameter of RSB in question. Specifically, more risk-taking was associated with more RSB. Furthermore, amount of recent cannabis use was associated with more RSB and sex-related negative consequences, but only among those with worse performances on a measure of decision-making and of risk-taking. Contrary to hypotheses, worse episodic memory also significantly predicted higher overall sexual-risk and decreased safe-sex practices. Results indicate that worse neurocognitive performance in the areas of risk-taking, decision-making, and episodic memory may influence the degree to which cannabis users engage in RSB and experience negative health consequences as a result. (JINS, 2012, 18, 1-7). PMID- 22676891 TI - Synthetic biology with RNA: progress report. AB - One of the long-term goals in synthetic biology is the construction of large scale gene networks to control and manipulate cells. Such networks often tweak natural regulatory mechanisms, or 'switches', in order to achieve the desired function. Regulatory mechanisms that involve RNA building blocks such as messenger RNA, microRNA and riboswitches have become increasingly prominent in this regard. Recent achievements include prototype mRNA sensors, logic circuits that respond to small molecule cues to affect cell fate, and cell-state classifier networks that identify physiological states using multiple microRNA inputs. This Review describes these and other results in RNA-based synthetic biology. PMID- 22676892 TI - Cross metathesis assisted solid-phase synthesis of glycopeptoids. AB - A solid-phase synthesis of glycopeptoids was explored through olefin cross metathesis (CM). Peptoids and sugar derivatives with appropriate olefin moieties were coupled in the presence of an olefin metathesis catalyst to afford glycopeptoids in good yields. This systematic solid-phase CM study can provide facile access to the molecular sources of glycopeptidomimetics and postchemical modifications on various molecular scaffolds. PMID- 22676890 TI - Synthetic in vitro circuits. AB - Inspired by advances in the ability to construct programmable circuits in living organisms, in vitro circuits are emerging as a viable platform for designing, understanding, and exploiting dynamic biochemical circuitry. In vitro systems allow researchers to directly access and manipulate biomolecular parts without the unwieldy complexity and intertwined dependencies that often exist in vivo. Experimental and computational foundations in DNA, DNA/RNA, and DNA/RNA/protein based circuitry have given rise to systems with more than 100 programmed molecular constituents. Functionally, they have diverse capabilities including: complex mathematical calculations, associative memory tasks, and sensing of small molecules. Progress in this field is showing that cell-free synthetic biology is a versatile testing ground for understanding native biological circuits and engineering novel functionality. PMID- 22676893 TI - Gastrointestinal stromal tumor of the rectum with scapular metastasis: a case report. AB - INTRODUCTION: Gastrointestinal stromal tumors are rare tumors. They commonly metastasize within the abdominal cavity, particularly to the liver. Less commonly, metastases can be found in the bone. CASE PRESENTATION: We here present a case of metastasis to the scapula in a 54-year-old Caucasian male patient with an advanced gastrointestinal stromal tumor, which was subsequently successfully treated with resection and sunitinib. CONCLUSION: The present study is, to the best of our knowledge, the second to describe scapular metastasis of a gastrointestinal stromal tumor. Our patient was treated by scapulectomy. The overwhelming majority of scapular tumors are metastases that arise from soft tissue, hepatocellular and thyroid tumors. Gastrointestinal stromal tumor metastasis occurs rarely. Scapular surgery can successfully provide local control of the disease. After the surgery, patients should continue with medical treatment. PMID- 22676894 TI - Develop of a multiway chemometric-based analytical method fulfilling regulatory identification criteria: application to GC-MS pesticide residue analysis. AB - The proposed procedure is described by applying it to develop an analytical method which fulfils the SANCO specifications. Nevertheless, the procedure would be valid for any other legal specification that requires the identification of the analyte by means its m/z values and retention time. To demonstrate the procedure, three herbicides (simazine, Sz; atrazine, Az; propazine, Pz), with terbuthylazine, Tz, as internal standard (IS) have been analysed by gas chromatography with mass spectrometry detection (GC/MS). The procedure consists of the following steps: (i) To record the data in the full scan mode (201 m/z ratios). (ii) To select four characteristic ions which make possible the unequivocal identification of each triazine according to the criteria established in the Document SANCO/12495/2011 by means of principal components and hierarchical clustering of variables; (iii) To build a calibration based on the PARAFAC decomposition with the data recorded in SIM mode at the four m/z ratios selected for each triazine. Afterwards several figures of merit have been evaluated. Bearing in mind that triazines are one of the most frequently used group of herbicides in agriculture and atrazine and simazine are included in the list of priority substances in Annex II of Directive 2008/105/EC, in this work, these analytes have been analysed in three natural waters. Prior to determination by gas chromatography with mass spectrometry detection (GC/MS) a step with solid phase extraction (SPE) has been carried out. The calibration set is made up of 40 standards 33 are external standards prepared in acetone and seven matrix matched prepared in deionised water subjected to the SPE procedure. Moreover, each kind of water, stream, well, and river, is analysed both unspiked and spiked. For the triazine determination, the second order PARAFAC advantage allows the use of samples prepared in acetone together with those prepared in deionised water subjected to SPE. The decision limit, CCalpha, and the capability of detection, CCbeta, are calculated according to ISO 11843-2, assessing the false positive and false negative. The m/z ratios chosen fulfils the SANCO identification criteria and also the spectrum obtained in the PARAFAC decomposition, which is common in all samples for each triazine. However, when the same experimental data are used to carry out a univariate calibration with the abundance of the base peak of each triazines, a lot of samples lie outside the permitted tolerances depending on the reference experimental spectra used, despite the fact that all of them have a triazine content above the detection limit. Also, the PARAFAC calibration allows us to detect the test samples which are not similar to the calibration samples and in this way their mistaken quantification is avoided. PMID- 22676896 TI - Cornelia de Lange syndrome with NIPBL mutation and mosaic Turner syndrome in the same individual. AB - BACKGROUND: Cornelia de Lange syndrome (CdLS) is a dominantly inherited disorder characterized by facial dysmorphism, growth and cognitive impairment, limb malformations and multiple organ involvement. Mutations in NIPBL gene account for about 60% of patients with CdLS. This gene encodes a key regulator of the Cohesin complex, which controls sister chromatid segregation during both mitosis and meiosis. Turner syndrome (TS) results from the partial or complete absence of one of the X chromosomes, usually associated with congenital lymphedema, short stature, and gonadal dysgenesis. CASE PRESENTATION: Here we report a four-year old female with CdLS due to a frameshift mutation in the NIPBL gene (c.1445_1448delGAGA), who also had a tissue-specific mosaic 45,X/46,XX karyotype. The patient showed a severe form of CdLS with craniofacial dysmorphism, pre- and post-natal growth delay, cardiovascular abnormalities, hirsutism and severe psychomotor retardation with behavioural problems. She also presented with minor clinical features consistent with TS, including peripheral lymphedema and webbed neck. The NIPBL mutation was present in the two tissues analysed from different embryonic origins (peripheral blood lymphocytes and oral mucosa epithelial cells). However, the percentage of cells with monosomy X was low and variable in tissues. These findings indicate that, ontogenically, the NIPBL mutation may have appeared before the mosaic monosomy X. CONCLUSIONS: The coexistence in several patients of these two rare disorders raises the issue of whether there is indeed a cause-effect association. The detailed clinical descriptions indicate predominant CdLS phenotype, although additional TS manifestations may appear in adolescence. PMID- 22676897 TI - Mitochondrial DNA content and mass increase in progression from normal to hyperplastic to cancer endometrium. AB - BACKGROUND: An increase in mitochondrial DNA (mtDNA) content and mitochondrial biogenesis associated with the activation of PGC-1alpha signalling pathway was previously reported in type I endometrial cancer. The aim of this study has been to evaluate if mtDNA content and the citrate synthase (CS) activity, an enzyme marker of mitochondrial mass, increase in progression from control endometrium to hyperplasia to type I endometrial carcinoma. RESULTS: Given that no statistically significant change in mtDNA content and CS activity in endometrium taken from different phases of the menstrual cycle or in menopause was found, these samples were used as control. Our research shows, for the first time, that mtDNA content and citrate synthase activity increase in hyperplastic endometrium compared to control tissues, even if their levels remain lower compared to cancer tissue. In particular, mtDNA content increases seem to precede increases in CS activity. No statistically significant change in mtDNA content and in CS activity was found in relation to different histopathological conditions such as grade, myometrial invasion and stage. CONCLUSION: MtDNA content and citrate synthase activity increases in pre-malignant lesions could be a potential molecular marker for progression from hyperplasia to carcinoma. PMID- 22676898 TI - Antiviral activity of salivary microRNAs for ophthalmic herpes zoster. AB - Ophthalmic herpes zoster is a common ocular infection caused by the varicella zoster virus (VZV). Viral mRNA transcripts play a major role in the replicative cycle of the virus and current antiviral agents have little effect in preventing and treating the complications. Therapeutic use of saliva for certain painful ocular diseases such as ophthalmic herpes zoster is a well-known public practice in our region. We thought that antiviral activity of saliva may stem from salivary microvesicles and we aimed to look for molecules with antiviral activity in these vesicles. As a possible candidate for antiviral activity, salivary microvesicles contain at least 20 microRNAs (miRNAs), small noncoding RNAs, which suppress the translation of target mRNAs. miRNAs not only participate in maintenance of normal cell functions, but are also involved in host-virus interactions and limit the replication of certain virus types. Thus, miRNA gene therapy by targeting mRNAs required for VZV survival may find a niche in the treatment of ophthalmic herpes zoster. But, how could salivary microvesicles reach into the corneal cells to demonstrate their antiviral activity. We suggest that human salivary microvesicles can be effective carriers of miRNA for corneal cells, because they contain a molecular machinery for vesicle trafficking and fusion allowing them to be endocytosed by target cells. After binding to the plasma membrane, microvesicles seem to enter into the corneal cells through the clathrin-mediated endocytosis. In the cytosol, human salivary miRNAs base-pair with specific viral mRNAs and inhibit their translation, thus limiting the replication of the virus. PMID- 22676900 TI - Food allergy and anaphylaxis meeting 2011 venice, Italy. 17-19 february 2011. Abstracts. PMID- 22676899 TI - The role of the circadian clock system in nutrition and metabolism. AB - Mammals have an endogenous timing system in the suprachiasmatic nuclei (SCN) of the hypothalamic region of the brain. This internal clock system is composed of an intracellular feedback loop that drives the expression of molecular components and their constitutive protein products to oscillate over a period of about 24 h (hence the term 'circadian'). These circadian oscillations bring about rhythmic changes in downstream molecular pathways and physiological processes such as those involved in nutrition and metabolism. It is now emerging that the molecular components of the clock system are also found within the cells of peripheral tissues, including the gastrointestinal tract, liver and pancreas. The present review examines their role in regulating nutritional and metabolic processes. In turn, metabolic status and feeding cycles are able to feed back onto the circadian clock in the SCN and in peripheral tissues. This feedback mechanism maintains the integrity and temporal coordination between various components of the circadian clock system. Thus, alterations in environmental cues could disrupt normal clock function, which may have profound effects on the health and well being of an individual. PMID- 22676901 TI - Montreal Cognitive Assessment (MoCA): validation study for vascular dementia. AB - The Montreal Cognitive Assessment (MoCA) is a brief instrument developed for the screening of milder forms of cognitive impairment, having surpassed the well known limitations of the MMSE. The aim of the present study was to validate the MoCA as well as its short version, which was proposed by the NINDS-CSN VCI Harmonization Standards for screening Vascular Dementia (VaD) patients. The results, based on a homogeneous sample of 34 VaD patients, indicate that the MoCA is a psychometrically valid and reliable instrument for cognitive screening in VaD patients, showing excellent discriminant validity. Both the full and short versions of the MoCA had excellent diagnostic accuracy in discriminating VaD patients, exhibiting an area under curve (AUC) higher than the MMSE [AUC(MoCA full version) = .950; 95% IC = .868-.988; AUC(MoCA short version) = .936; 95% IC = .849-.981; AUC(MMSE) = .860; 95% IC = .754-.932]. With a cutoff below 17 on the MoCA full version and 8 on the short version, the results for sensitivity, specificity, positive and negative predictive values, and classification accuracy were superior compared to the MMSE. In conclusion, both versions of the MoCA are valid, reliable, sensitive and accurate screening instruments for VaD patients. PMID- 22676902 TI - The effects of long-term exposure of magnetic field via 900-MHz GSM radiation on some biochemical parameters and brain histology in rats. AB - The aim of this study is to determine the effects of magnetic field via cell phones on some blood parameters and neurons in the brain of rats. Animals have been classified into three groups: control, Magnetic Field (MF), and F2 groups. Throughout this study, cell phones were placed on the wall of the cages. Rats were exposed to the effects of cell phones during prenatal and postnatal periods until they were 80 days old. During the study, the exposure procedure of rats was that the phone was in standby mode for a whole day and in talking mode for 30 min per day. The waves of cell phones caused an increased blood glucose level from 96.52 +/- 5.64 mg/dl to 132.14 +/- 5.93 mg/dl and an increased serum protein level from 131.14 +/- 6.19 mg/dl to 319.29 +/- 6.73 mg/dl compared to control. Statistically, significant differences wasn't observed in the blood cholesterol concentration between the groups compared to the control. Weekly weight gain decreased in all groups compared to the control. MF exposure decreased pyramidal neuron numbers 51.15% and increased ischemic neuron numbers 73% at cortex region of brain. In addition, vascular dilatations have increased clearly in group F2.Whereas the procedure of MF did not have any effects on hippocampal pyramidal cell numbers, magnetic fields increased the amount of ischemic neurons three-fold compared to the control. In conclusion, MF affected some biochemical parameters, especially the cortex region of the brain. PMID- 22676903 TI - Progressive structure-based alignment of homologous proteins: Adopting sequence comparison strategies. AB - Comparison of multiple protein structures has a broad range of applications in the analysis of protein structure, function and evolution. Multiple structure alignment tools (MSTAs) are necessary to obtain a simultaneous comparison of a family of related folds. In this study, we have developed a method for multiple structure comparison largely based on sequence alignment techniques. A widely used Structural Alphabet named Protein Blocks (PBs) was used to transform the information on 3D protein backbone conformation as a 1D sequence string. A progressive alignment strategy similar to CLUSTALW was adopted for multiple PB sequence alignment (mulPBA). Highly similar stretches identified by the pairwise alignments are given higher weights during the alignment. The residue equivalences from PB based alignments are used to obtain a three dimensional fit of the structures followed by an iterative refinement of the structural superposition. Systematic comparisons using benchmark datasets of MSTAs underlines that the alignment quality is better than MULTIPROT, MUSTANG and the alignments in HOMSTRAD, in more than 85% of the cases. Comparison with other rigid-body and flexible MSTAs also indicate that mulPBA alignments are superior to most of the rigid-body MSTAs and highly comparable to the flexible alignment methods. PMID- 22676904 TI - Medical rehabilitation after natural disasters: why, when, and how? AB - Natural disasters can cause significant numbers of severe, disabling injuries, resulting in a public health emergency and requiring foreign assistance. However, since medical rehabilitation services are often poorly developed in disaster affected regions and not highly prioritized by responding teams, physical and rehabilitation medicine (PRM) has historically been underemphasized in global disaster planning and response. Recent development of the specialties of "disaster medicine" and "disaster rehabilitation" has raised awareness of the critical importance of rehabilitation intervention during the immediate postdisaster emergency response. The World Health Organization Liaison Sub Committee on Rehabilitation Disaster Relief of the International Society of Physical and Rehabilitation Medicine has authored this report to assess the role of emergency rehabilitation intervention after natural disasters based on current scientific evidence and subject matter expert accounts. Major disabling injury types are identified, and spinal cord injury, limb amputation, and traumatic brain injury are used as case studies to exemplify the challenges to effective management of disabling injuries after disasters. Evidence on the effectiveness of disaster rehabilitation interventions is presented. The authors then summarize the current state of disaster-related research, as well as lessons learned from PRM emergency rehabilitation response in recent disasters. Resulting recommendations for greater integration of PRM services into the immediate emergency disaster response are provided. This report aims to stimulate development of research and practice in the emerging discipline of disaster rehabilitation within organizations that provide medical rehabilitation services during the postdisaster emergency response. PMID- 22676905 TI - Simplified cough test for screening silent aspiration. AB - OBJECTIVE: To simplify the cough test to screen silent aspiration without sacrificing accuracy. DESIGN: Criterion standard. SETTING: University dental hospital. PARTICIPANTS: Consecutive patients (N=141; 92 men, 49 women; mean age 71+/-14y, range 23-94y) who had complained of some dysphagic symptoms between June 2008 and February 2010. INTERVENTIONS: All patients were administrated a simplified cough test and underwent the fiberoptic endoscopic evaluation of swallowing. Citric acid inhalation was terminated when the first cough occurred, and the time between the start of inhalation and the first cough was measured. MAIN OUTCOME MEASURES: The time when the first cough was observed by the simplified cough test was compared with the results of the fiberoptic endoscopic evaluation of swallowing, which was used as a criterion standard. RESULTS: Receiver operating characteristic curve analysis was performed for 53 patients evaluated as having aspiration by fiberoptic endoscopic evaluation of swallowing. We found that 30 seconds or less was an appropriate cutoff value for detecting patients without silent aspiration, where the sensitivity was .92 and the specificity was .94. From the receiver operating characteristic curve analyses for all patients, 60 seconds or less was determined to be an appropriate cutoff, and the sensitivity and specificity were .81 and .65, respectively. CONCLUSION: The simplified cough test is a useful screening tool for silent aspiration in patients with aspiration. PMID- 22676906 TI - Can surface neuromuscular electrical stimulation of the wrist and hand combined with routine therapy facilitate recovery of arm function in patients with stroke? AB - OBJECTIVE: To investigate whether treatment with surface neuromuscular electrical stimulation to the wrist extensors improves recovery of arm function in severely disabled patients with stroke. DESIGN: Single blinded randomized controlled trial. SETTING: Acute stroke unit and stroke rehabilitation wards of a university hospital. PARTICIPANTS: Patients with no upper limb function (Action Research Arm Test [ARAT] score 0) (N=90; mean age +/- SD, 74+/-11y; 49% men) were recruited to the study within 6 weeks of stroke. Only 67 participants were alive at the end of the study and data from 66 of these people were analyzed. INTERVENTIONS: Participants were randomized to surface neuromuscular electrical stimulation using surface electrical stimulators for 30 minutes, twice in a working day for 6 weeks in addition to standardized upper limb therapy or just standardized upper limb therapy. MAIN OUTCOME MEASURE: The primary outcome measure was the ARAT score. Assessments were made at baseline and at 6, 12, 24, and 36 weeks after recruitment. RESULTS: There were statistically significant improvements in measures of wrist extensor (mean difference 0.5; 95% confidence interval [CI], 0.0-1.0) and grip strength (mean difference 0.9; 95% CI, 0.1-1.7) over the treatment period. Arm function (ARAT score) was not significantly different between the groups over the treatment period at 6 weeks (mean difference 1.9; 95% CI, -2.9 to 6.8) or over the study period at 36 weeks (mean difference 6.4; 95% CI, -1.8 to 14.7), and the rate of recovery was not significantly different (mean difference 0.7; 95% CI, -0.2 to 1.6). CONCLUSIONS: In patients with severe stroke, with no functional arm movement, electrical stimulation of wrist extensors improves muscle strength for wrist extension and grip, and larger studies are required to study its influence on arm function. PMID- 22676907 TI - Abstracts of the 17th International Symposium on HIV and Emerging Infectious Diseases (ISHEID). Marseille, France. May 23-25, 2012. PMID- 22676908 TI - Endoscopic surgery versus conservative treatment for the moderate-volume hematoma in spontaneous basal ganglia hemorrhage (ECMOH): study protocol for a randomized controlled trial. AB - BACKGROUND: Spontaneous intracerebral hemorrhage is a disease with high morbidity, high disability rate, high mortality, and high economic burden. Whether patients can benefit from surgical evacuation of hematomas is still controversial, especially for those with moderate-volume hematomas in the basal ganglia. This study is designed to compare the efficacy of endoscopic surgery and conservative treatment for the moderate-volume hematoma in spontaneous basal ganglia hemorrhage. METHODS: Patients meet the criteria will be randomized into the endoscopic surgery group (endoscopic surgery for hematoma evacuation and the best medical treatment) or the conservative treatment group (the best medical treatment). Patients will be followed up at 1, 3, and 6 months after initial treatment. The primary outcomes include the Extended Glasgow Outcome Scale and the Modified Rankin Scale. The secondary outcomes consist of the National Institutes of Health Stroke Scale and the mortality. The Barthel Index(BI) will also be evaluated. The sample size is 100 patients. DISCUSSION: The ECMOH trial is a randomized controlled trial designed to evaluate if endoscopic surgery is better than conservative treatment for patients with moderate-volume hematomas in the basal ganglia. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR TRC-11001614(http://www.chictr.org/en/proj/show.aspx?proj=1618). PMID- 22676910 TI - Polyphenol-rich extract of pomegranate peel alleviates tissue inflammation and hypercholesterolaemia in high-fat diet-induced obese mice: potential implication of the gut microbiota. AB - Pomegranate extracts have been used for centuries in traditional medicine to confer health benefits in a number of inflammatory diseases, microbial infections and cancer. Peel fruit are rich in polyphenols that exhibit antioxidant and anti inflammatory capacities in vitro. Recent studies strongly suggest that the gut microbiota is an environmental factor to be taken into account when assessing the risk factors related to obesity. The aim of the present study was to test the prebiotic potency of a pomegranate peel extract (PPE) rich in polyphenols in a nutritional model of obesity associated with hypercholesterolaemia and inflammatory disorders. Balb/c mice were fed either a control diet or a high-fat (HF) diet with or without PPE (6 mg/d per mouse) over a period of 4 weeks. Interestingly, PPE supplementation increased caecal content weight and caecal pool of bifidobacteria. It did not significantly modify body weight gain, glycaemia, glucose tolerance and inflammatory markers measured in the serum. However, it reduced the serum level of cholesterol (total and LDL) induced by HF feeding. Furthermore, it counteracted the HF-induced expression of inflammatory markers both in the colon and the visceral adipose tissue. Together, these findings support that pomegranate constitutes a promising food in the control of atherogenic and inflammatory disorders associated with diet-induced obesity. Knowing the poor bioavailability of pomegranate polyphenols, its bifidogenic effect observed after PPE consumption suggests the involvement of the gut microbiota in the management of host metabolism by polyphenolic compounds present in pomegranate. PMID- 22676911 TI - TRAIL as biomarker and potential therapeutic tool for cardiovascular diseases. AB - This review focuses on TNF-related apoptosis-inducing ligand (TRAIL), also called Apo2 ligand, a protein belonging to the TNF superfamily. TRAIL can be found either in its transmembrane or circulating form, and its mostly studied peripheral effect is the induction of cellular apoptosis. Here, we discuss the evidences supporting the use of TRAIL as biomarker of cardiovascular diseases as well as the evidences showing the potential beneficial therapeutic effects of TRAIL on cardiovascular diseases and diabetes. PMID- 22676909 TI - Development of a prediction model for 10-year risk of hepatocellular carcinoma in middle-aged Japanese: the Japan Public Health Center-based Prospective Study Cohort II. AB - OBJECTIVE: The purpose of the present study was to develop a risk estimation model for the 10-year risk of hepatocellular carcinoma (HCC) that could be easily used in a general population to aid in the prevention of HCC. METHODS: Our prediction model was derived from data obtained on 17,654 Japanese aged 40 to 69 years who participated in health checkups (follow-up: 1993-2006). Cox proportional hazards regression was applied to obtain coefficients for each predictor. RESULTS: During follow-up, a total of 104 cases of HCC were newly diagnosed. After checking the model fit, we incorporated age, sex, alcohol consumption, body mass index, diabetes, coffee consumption, and hepatitis B and C virus infection into the prediction model. The model showed satisfactory discrimination (Harrell's c-index=0.94) and was well calibrated (the overall observed/expected ratio=1.03, 95% confidence interval=0.83-1.29). We also developed a simple risk scoring system. Those subjects with total scores of 17 or more under this system (score range: -1 to 19) had an estimated 10-year HCC risk of over 90%; those with 4 points or less had an estimated risk of less than 0.1%. CONCLUSION: We developed a simple 10-year risk prediction model for HCC in the Japanese general population as a public education tool. PMID- 22676912 TI - Novel chelators targeting cell cycle arrest, acetylcholinesterase, and monoamine oxidase for Alzheimer's therapy. AB - The recent finding that acetylcholinesterase (AChE) colocalizes with beta-amyloid (Abeta), promotes and accelerates Abeta aggregation has renewed an intense interest in developing new multitarget AChE inhibitors as potential disease modifying drugs for Alzheimer's therapy. In this review, we first briefly discuss the linkage and complex interplay among the three characteristic hallmarks of Alzheimer's disease (AD): amyloid (Abeta) plaques, neurofibrillary tangles (NFTs), and cholinergic hypofunction. We then review the recent studies on the four marketed cholinesterase inhibitors in term of their multiple activities, potential disease-modifying effects, and the underlying mechanisms of these actions. We finally focus on a new emerging strategy or multitarget AChE inhibitors as effective drugs for AD therapy. We explore some examples of multitarget ChE inhibitors developed in our own and other laboratories, which were purposely designed to address multiple AD etiological targets. These new AChE inhibitors hold great promise for improving cognitive functions in AD patients, slowing down the disease progression, as well as treating behavior problems related to AD. PMID- 22676913 TI - Molecular dynamics and mutational analysis of the catalytic and translocation cycle of RNA polymerase. AB - BACKGROUND: During elongation, multi-subunit RNA polymerases (RNAPs) cycle between phosphodiester bond formation and nucleic acid translocation. In the conformation associated with catalysis, the mobile "trigger loop" of the catalytic subunit closes on the nucleoside triphosphate (NTP) substrate. Closing of the trigger loop is expected to exclude water from the active site, and dehydration may contribute to catalysis and fidelity. In the absence of a NTP substrate in the active site, the trigger loop opens, which may enable translocation. Another notable structural element of the RNAP catalytic center is the "bridge helix" that separates the active site from downstream DNA. The bridge helix may participate in translocation by bending against the RNA/DNA hybrid to induce RNAP forward movement and to vacate the active site for the next NTP loading. The transition between catalytic and translocation conformations of RNAP is not evident from static crystallographic snapshots in which macromolecular motions may be restrained by crystal packing. RESULTS: All atom molecular dynamics simulations of Thermus thermophilus (Tt) RNAP reveal flexible hinges, located within the two helices at the base of the trigger loop, and two glycine hinges clustered near the N-terminal end of the bridge helix. As simulation progresses, these hinges adopt distinct conformations in the closed and open trigger loop structures. A number of residues (described as "switch" residues) trade atomic contacts (ion pairs or hydrogen bonds) in response to changes in hinge orientation. In vivo phenotypes and in vitro activities rendered by mutations in the hinge and switch residues in Saccharomyces cerevisiae (Sc) RNAP II support the importance of conformational changes predicted from simulations in catalysis and translocation. During simulation, the elongation complex with an open trigger loop spontaneously translocates forward relative to the elongation complex with a closed trigger loop. CONCLUSIONS: Switching between catalytic and translocating RNAP forms involves closing and opening of the trigger loop and long-range conformational changes in the atomic contacts of amino acid side chains, some located at a considerable distance from the trigger loop and active site. Trigger loop closing appears to support chemistry and the fidelity of RNA synthesis. Trigger loop opening and limited bridge helix bending appears to promote forward nucleic acid translocation. PMID- 22676915 TI - Effects of 50 Hz pulsed electromagnetic fields on the growth and cell cycle arrest of mesenchymal stem cells: an in vitro study. AB - Mesenchymal stem cells (MSCs) are capable of self-renew and multipotent differatiation which allows them to be sensitive to microenvironment is altered. Pulsed electromagnetic fields (PEMF) can affect cellular physiology of some types of cells. This study was undertaken to investigate the effects of PEMF on the growth and cell cycle arrest of MSCs expanded in vitro. To achieve this, cultured of normal rat MSCs, the treatment groups were respectively irradiated by 50 Hz PEMF at 10 mT of flux densities for 3 or 6 h. The effects of PEMF on cell proliferation, cell cycle arrest, and cell surface antigen phenotype were investigated. Our results showed that exposed MSCs had a significant proliferative capacity (P < 0.05) but the effect of PEMF for 3 and 6 h on cell growth was not different (P>0.05) at an earlier phase after PEMF treatment. Exposure to PEMF had a significant increase the percentage of MSCs in G1 phase compare with the control group, with a higher percentage of cells in G1 phase exposed for 6 h then that for 3 h. At the 16th hour after treatment, PEMF had no significant effect on cell proliferation and cell cycle (P>0.05). These results suggested that PEMF enhanced MSCs proliferation with time-independent and increased the percentage of cells at the G1 phase of the cell cycle in a time dependent manner, and the effect of PEMF on the cell proliferation and cell cycle arrest of MSCs was temporal after PEMF treatment. PMID- 22676914 TI - Association between cognitive activity and cognitive function in older Hispanics. AB - There is limited research on the association between participation in cognitively stimulating activity and cognitive function in older Hispanics. The main purpose of the present study was to explore whether frequency of cognitive activity and its association with cognitive function in Hispanics is comparable to that of non Hispanics. In a multiethnic cohort of 1571 non-demented older adults, we assessed past and current cognitive activity, availability of cognitive resources in the home in childhood and middle age, and five domains of cognitive function. The measures of cognitive activity and cognitive resources had adequate reliability and validity in our subset of Hispanic participants (n = 81). Hispanics reported lower levels of education, lower frequency of cognitive activity and less cognitive resources than non-Hispanic White (n = 1102) and non-Hispanic Black (n = 388) participants. Despite these differences the strength of the association between cognitive activity and cognitive function was comparable across ethnic groups. Because Hispanics have lower frequency of cognitive activity, the benefit of cognitive activity to late life cognitive function may be potentially larger in this segment of the population. Thus, interventions aimed at increasing frequency of participation in cognitively stimulating activity may offer a potential target to reduce cognitive impairment in Hispanics. PMID- 22676916 TI - Alternative sumoylation sites in the Drosophila nuclear receptor Usp. AB - The ultraspiracle protein (Usp), together with an ecdysone receptor (EcR) forms a heterodimeric ecdysteroid receptor complex, which controls metamorphosis in Drosophila melanogaster. Although the ecdysteroid receptor is considered to be a source of elements for ecdysteroid inducible gene switches in mammals, nothing is known about posttranslational modifications of the receptor constituents in mammalian cells. Up until now there has been no study about Usp sumoylation. Using Ubc9 fusion-directed sumoylation system, we identified Usp as a new target of SUMO1 and SUMO3 modification. Mutagenesis studies on the fragments of Usp indicated that sumoylation can occur alternatively on several defined Lys residues, i.e. three (Lys16, Lys20, Lys37) in A/B region, one (Lys424) in E region and one (Lys506) in F region. However, sumoylation of one Lys residue within A/B region prevents modification of other residues in this region. This was also observed for Lys residues in carboxyl-terminal fragment of Usp, i.e. comprising E and F regions. Mass spectrometry analysis of the full-length Usp indicated that the main SUMO attachment site is at Lys20. EcR, the heterodimerization partner of Usp, and muristerone A, the EcR ligand, do not influence sumoylation patterns of Usp. Another heterodimerization partner of Usp HR38 fused with Ubc9 interacts with Usp in HEK293 cells and allows sumoylation of Usp independent of the direct fusion to Ubc9. Taken together, we propose that sumoylation of DmUsp can be an important factor in modulating its activity by changing molecular interactions. PMID- 22676917 TI - Characterization of MgNd2 alloy for potential applications in bioresorbable implantable devices. AB - The aim of this study is to investigate and demonstrate the mechanical and corrosive characteristics of the neodymium-containing magnesium alloy MgNd2 (Nd2), which can be used as a resorbable implant material, especially in the field of stenting applications. To determine the mechanical characteristics of Nd2, tensile and compression tests were initially carried out in the hot extruded state. Here a unique elongation ratio (~30%) of the alloy could be observed. Subsequent T5 and T6 heat treatments were arranged to reveal their effect on the alloy's strengths and elongation values. The general degradation behaviour of Nd2 in a 0.9% NaCl solution was investigated by means of polarization curves and hydrogen evolution. In addition to this, by using various in vivo parameters, a corrosion environment was established to determine the alloy's degradation in vitro. Here, the mass loss per day in (MgF(2) and Bioglass)-coated and uncoated states and the corresponding maximum forces resulting from subsequent three-point bending tests revealed slow and steady corrosion behaviour. The cell viability and proliferation tests carried out on L-929 and MSC-P5 cells also showed good results. The mechanical and corrosive characteristics determined, as well as the in vitro test results obtained within the scope of this study, led to the development and successful in vivo testing of an MgF(2)-coated Nd2 mucosa stent which was introduced as an appropriate resorbable application. PMID- 22676918 TI - Early stage mineralization in tissue engineering mapped by high resolution X-ray microdiffraction. AB - The specific routes of biomineralization in nature are here explored using a tissue engineering approach in which bone is formed in porous ceramic constructs seeded with bone marrow stromal cells and implanted in vivo. Unlike previous studies this model system reproduces mammalian bone formation, here investigated at high temporal resolution. Different mineralization stages were monitored at different distances from the scaffold interface so that their spatial analysis corresponded to temporal monitoring of the bone growth and mineralization processes. The micrometer spatial resolution achieved by our diffraction technique ensured highly accurate reconstruction of the different temporal mineralization steps and provided some hints to the challenging issue of the mineral deposit first formed at the organic-mineral interface. Our results indicated that in the first stage of biomineralization organic tissue provides bioavailable calcium and phosphate ions, ensuring a constant reservoir of amorphous calcium phosphate (ACP) during hydroxyapatite (HA) nanocrystal formation. In this regard we suggest a new role of ACP in HA formation, with a continuous organic-mineral transition assisted by a dynamic pool of ACP. After HA nanocrystals formed, the scaffold and collagen act as templates for nanocrystal arrangement on the microscopic and nanometric scales, respectively. PMID- 22676919 TI - Body iron is associated with cognitive executive planning function in college women. AB - Evidence of the relationship between altered cognitive function and depleted Fe status is accumulating in women of reproductive age but the degree of Fe deficiency associated with negative neuropsychological outcomes needs to be delineated. Data are limited regarding this relationship in university women in whom optimal cognitive function is critical to academic success. The aim of the present study was to examine the relationship between body Fe, in the absence of Fe-deficiency anaemia, and neuropsychological function in young college women. Healthy, non-anaemic undergraduate women (n 42) provided a blood sample and completed a standardised cognitive test battery consisting of one manual (Tower of London (TOL), a measure of central executive function) and five computerised (Bakan vigilance task, mental rotation, simple reaction time, immediate word recall and two-finger tapping) tasks. Women's body Fe ranged from - 4.2 to 8.1 mg/kg. General linear model ANOVA revealed a significant effect of body Fe on TOL planning time (P= 0.002). Spearman's correlation coefficients showed a significant inverse relationship between body Fe and TOL planning time for move categories 4 (r - 0.39, P= 0.01) and 5 (r - 0.47, P= 0.002). Performance on the computerised cognitive tasks was not affected by body Fe level. These findings suggest that Fe status in the absence of anaemia is positively associated with central executive function in otherwise healthy college women. PMID- 22676920 TI - Functional electrical stimulation mediated by iterative learning control and 3D robotics reduces motor impairment in chronic stroke. AB - BACKGROUND: Novel stroke rehabilitation techniques that employ electrical stimulation (ES) and robotic technologies are effective in reducing upper limb impairments. ES is most effective when it is applied to support the patients' voluntary effort; however, current systems fail to fully exploit this connection. This study builds on previous work using advanced ES controllers, and aims to investigate the feasibility of Stimulation Assistance through Iterative Learning (SAIL), a novel upper limb stroke rehabilitation system which utilises robotic support, ES, and voluntary effort. METHODS: Five hemiparetic, chronic stroke participants with impaired upper limb function attended 18, 1 hour intervention sessions. Participants completed virtual reality tracking tasks whereby they moved their impaired arm to follow a slowly moving sphere along a specified trajectory. To do this, the participants' arm was supported by a robot. ES, mediated by advanced iterative learning control (ILC) algorithms, was applied to the triceps and anterior deltoid muscles. Each movement was repeated 6 times and ILC adjusted the amount of stimulation applied on each trial to improve accuracy and maximise voluntary effort. Participants completed clinical assessments (Fugl Meyer, Action Research Arm Test) at baseline and post-intervention, as well as unassisted tracking tasks at the beginning and end of each intervention session. Data were analysed using t-tests and linear regression. RESULTS: From baseline to post-intervention, Fugl-Meyer scores improved, assisted and unassisted tracking performance improved, and the amount of ES required to assist tracking reduced. CONCLUSIONS: The concept of minimising support from ES using ILC algorithms was demonstrated. The positive results are promising with respect to reducing upper limb impairments following stroke, however, a larger study is required to confirm this. PMID- 22676922 TI - Color-coding triage and allergic reactions in an Italian ED. PMID- 22676921 TI - Impact on postpartum hemorrhage of prophylactic administration of oxytocin 10 IU via UnijectTM by peripheral health care providers at home births: design of a community-based cluster-randomized trial. AB - BACKGROUND: Hemorrhage is the leading direct cause of maternal death globally. While oxytocin is the drug of choice for postpartum hemorrhage prevention, its use has generally been limited to health facilities. This trial assesses the effectiveness, safety, and feasibility of expanding the use of prophylactic intramuscular oxytocin to peripheral health care providers at home births in four predominantly rural districts in central Ghana. METHODS: This study is designed as a community-based cluster-randomized trial in which Community Health Officers are randomized to provide (or not provide) an injection of oxytocin 10 IU via the UnijectTM injection system within one minute of delivery of the baby to women who request their presence at home at the onset of labor. The primary aim is to determine if administration of prophylactic oxytocin via UnijectTM by this cadre will reduce the risk of postpartum hemorrhage by 50 % relative to deliveries which do not receive the prophylactic intervention. Postpartum hemorrhage is examined under three sequential definitions: 1) blood loss >=500 ml (BL); 2) treatment for bleeding (TX) and/or BL; 3) hospital referral for bleeding and/or TX and/or BL. Secondary outcomes address safety and feasibility of the intervention and include adverse maternal and fetal outcomes and logistical concerns regarding assistance at home births and the storage and handling of oxytocin, respectively. DISCUSSION: Results from this trial will build evidence for the effectiveness of expanding the delivery of this established prophylactic intervention to peripheral settings. Complementary data on safety and logistical issues related to this intervention will assist policymakers in low-income countries in selecting both the best uterotonic and service delivery strategy for postpartum hemorrhage prevention. Results of this trial are expected in mid-2013. The trial is registered at ClinicalTrials.gov: NCT01108289. PMID- 22676923 TI - Form, content and style: rendering research into publication. PMID- 22676924 TI - Clinical analysis of 120 cases of intraoral lymphoepithelial cyst. AB - OBJECTIVE: The aim of this study was to analyze a single institution's experience in the clinical management of intraoral lymphoepithelial cyst (LEC). STUDY DESIGN: From 1993 to 2010, a total of 120 consecutive patients with intraoral LEC underwent surgery and were retrospectively investigated regarding its clinical appearance, clinical differential diagnosis, treatment, and prognosis. RESULTS: Of the 120 patients, 37 were male and 83 female, their ages ranging from 2 to 75 years with a mean of 44.1 years. The most common locations were the tongue (50%) and floor of mouth (38.3%). The course of disease ranged from 2 months to 10 years with a mean of 8.0 months, and 75.8% of the patients had a course of disease <6 months. Routine laboratory examinations were within normal limits. All patients underwent complete surgical removal of the lesions. During the follow-up period, no lesion recurrence occurred, and the quality of life of each patient was good. CONCLUSIONS: The clinical characteristics of intraoral LEC are not specific and may be confused with other intraoral lesions. The first choice of treatment is surgical excision, which results in a good prognosis. PMID- 22676925 TI - Position and course of the mandibular canal in skulls. AB - OBJECTIVE: The aim of this study was to examine and describe the topography of the mandibular canal (MC) in both vertical and occlusal dimensions. STUDY DESIGN: Fifty-two adult skulls deposited in the University of Pittsburgh School of Dental Medicine skull collection were evaluated in this study. Cone-beam computerized tomographic scans of each skull were obtained. RESULTS: The vertical course of MC was classified into 3 types: straight projection (12.2%), catenary-like configuration (51.1%), and progressive descent from posterior to anterior (36.7%). The evaluation of the buccolingual dimension showed that the mandibular canal was located either in contact with or close to the lingual cortical plate (<= 2 mm) in the molar region of the majority of the cases. As it proceeds anteriorly it moves toward the buccal aspect of the mandible, where it finally emerges through the mental foramen. Three emerging patterns of mandibular canal were observed: sharp turn (53.2%), soft curved exit (28.8%), and straight path (17.4%). The examination of the vertical dimension showed that the canal was located almost 1 cm above the inferior border of the mandible and then ascended to reach the mental foramen, which is located ~16 mm (range 13.4-20.3 mm) above the inferior border of the mandible. We found a strong correlation between height of the mandible and location of the mental foramen (r = 0.64; P < .0001). CONCLUSIONS: The course of mandibular canal described in vertical and axial dimensions and variation in its path have been classified. In addition to variation in location of MC, it has different anatomic configurations which clinicians should be familiar with in any surgical procedures involving the posterior mandible. PMID- 22676926 TI - Restoration of a peri-implant defect by platelet-rich fibrin. AB - OBJECTIVE: The objective of this study was to evaluate the application of platelet-rich fibrin (PRF) into a peri-implant defect in vivo. STUDY DESIGN: Eight New Zealand white rabbits were used for this study. Two peri-implants with defects sized 3.0 * 5.0 mm (width * length) were prepared after drilling to host the dental implant in the tibia. Subsequently, the 2 dental implants were installed (diameter, 3.0 mm and length, 8.0 mm). In the experimental group, PRF was applied into the bony defect. In the control group, the peri-implant defect was left unfilled. The animals were humanely killed 8 weeks after implantation and histomorphometric analysis was done. RESULTS: In the histomorphometric analysis, mean new bone formation was 29.30% +/- 7.50% in the experimental group and 11.06% +/- 8.94% in the control group (P = .020). Mean bone-to-implant contact was 39.43% +/- 7.39% in the experimental group and 17.11% +/- 8.12% in the control group (P = .006). CONCLUSIONS: In the animal model, peri-implant defect sized 3.0 * 5.0 mm (width * length) was successfully repaired by the application of PRF alone. PMID- 22676927 TI - Correlation of metabolism/hypoxia markers and fluorodeoxyglucose uptake in oral squamous cell carcinomas. AB - OBJECTIVE: The objective of this study was to analyze the relationship between the uptake of (18)F-2-fluoro-2-deoxy-d-glucose (FDG) by positron emission tomography-computerized tomography (PET-CT) and glucose metabolism/hypoxia markers in oral squamous cell carcinoma (OSCC). STUDY DESIGN: Thirty-six patients with OSCC (tongue [n = 23], buccal mucosa [n = 7], and floor of the mouth [n = 6]) were assessed and underwent incisional biopsy and subsequently received FDG PET-CT. Expressions of hypoxia-inducible factor 1alpha (HIF-1alpha), glucose transporter protein 1 (GLUT-1), hexokinase-II (HK-II), and glucose-6-phosphatase (G6Pase) were immunohistochemically quantified, and FDG uptake was evaluated by the maximum standardized uptake values (SUV(max)) at the primary tumor site. RESULTS: FDG uptake was found to be significantly correlated with the T classification of OSCC but not with other clinicopathologic characteristics, such as the N classification, clinical type, and histologic grade of malignancy. In the early-stage (T1 and T2) tumor, FDG uptake was significantly associated with the expression levels of GLUT-1, HK II, and HIF-1alpha, and the expression levels of GLUT-1 and HK-II significantly correlated with HIF-1alpha expression levels. However, there were no correlations between the expression levels of these molecules and SUV(max) in the late-stage (T3 and T4) tumor. CONCLUSIONS: FDG uptake was significantly associated with the expression levels of glucose metabolism-related molecules, such as GLUT-1, HK II, and HIF-1alpha, especially in early-stage tumors. PMID- 22676928 TI - Histomorphometric analysis of new bone obtained by osteogenic periosteal distraction in ovariectomized rabbits. AB - OBJECTIVE: The aim of this study was to evaluate the effects of estrogen deficiency on newly formed bone obtained by osteogenic periosteal distraction histomorphometrically. STUDY DESIGN: Thirty-six female rabbits were divided into 2 groups. The experimental group underwent a bilateral ovariectomy and a sham operation was applied to the control group to equalize the stress of ovariectomy surgery. Four weeks postoperatively, a gradual distraction of the mandibular corpus was performed. RESULTS: In the experimental group, callus formation was delayed and the new bone was less mineralized; conversely, when histomorphometric measurements were compared statistically, there were no significant differences between the ovariectomized and sham-operated subgroups in the mean extent of newly formed bone tissue. CONCLUSIONS: Although osteoporosis caused by the lack of estrogen has negative effects on osteogenic periosteal distraction (OPD), these negative effects do not appear to present a contraindication to OPD. PMID- 22676929 TI - Osteoinductive activity of biphasic calcium phosphate with different rhBMP-2 doses in rats. AB - OBJECTIVE: The aim of the current study was to determine whether a hydroxyapatite (HA)/beta-tricalcium phosphate (beta-TCP) ratio of 20/80 impregnated with recombinant human bone morphogenetic protein (rhBMP-2) enhances new bone formation and to evaluate the dose-dependent response of rhBMP-2. STUDY DESIGN: Critical-sized calvarial defects were made in rats, and biphasic calcium phosphate (BCP) with different rhBMP-2 doses was loaded into rat calvarial defects. The animals were allowed to heal for either 2 or 8 weeks. RESULTS: The percentages of new bone after 2 and 8 weeks of healing were significantly greater in the rhBMP-2-treated groups (at all doses) than in the control groups. The percentage of remaining BCP was significantly lower at 8 weeks than at 2 weeks in all groups that included BCP. CONCLUSIONS: rhBMP-2 administered using a BCP carrier significantly induces new bone formation. A dose-dependent response was not shown in the present study. PMID- 22676930 TI - Clinical and histologic evaluation of effects of hyaluronic acid in rat tongue. AB - OBJECTIVE: This study aimed to investigate local and systemic effects of 2 concentrations of hyaluronic acid (HA) in rats. STUDY DESIGN: Fifty-four female Wistar rats were allocated to 3 treatment groups (25 mg/mL HA, 5.5 mg/mL HA, and 0.9% NaCl) and 3 subgroups of experimental time (7, 60, and 90 days). The rats were evaluated clinically and then killed. The tongue and right kidney were removed and stained by hematoxylin and eosin and picrosirius (tongue only). RESULTS: The clinical changes did not differ significantly between groups (Kruskal-Wallis: P > .05). Histologically there was significantly greater inflammatory response in the groups with HA compared with control (Kruskal Wallis: P < .001). All kidney samples were normal. The 25 mg/mL HA group had higher collagen formation (analysis of variance mixed models: P = .016). CONCLUSIONS: HA causes moderate inflammatory reaction to 7 days and mild to 60 and 90 days, which is compatible with tissue repair, and a slightly increased collagen formation around the material was detected. PMID- 22676931 TI - Comparison of 4% articaine with epinephrine (1:100,000) and without epinephrine in inferior alveolar block for tooth extraction: double-blind randomized clinical trial of anesthetic efficacy. AB - OBJECTIVE: The purpose of this clinical prospective, randomized, double-blind study was to compare the anesthetic efficacy of 4% articaine with epinephrine (1:100,000) and without epinephrine in inferior alveolar nerve block anesthesia for extractions of mandibular teeth. STUDY DESIGN: Eighty-eight patients received intraoral inferior alveolar nerve blocks using 4% articaine with 1:100,000 epinephrine (n = 41; group 1) or without epinephrine (n = 47; group 2) for extractions of mandibular teeth. The primary objectives were differences in onset as well as in length of soft tissue anesthesia. The amount of anesthetic solution, need of a second injection, pain while injecting, pain during treatment, postoperative pain, and possible complications were surveyed. RESULTS: In both groups, anesthesia was sufficient for dental extractions. In group 1, a significantly faster onset of the anesthetic effect (7.2 min vs. 9.2 min; P = .001) and a significantly longer duration of soft tissue anesthesia (3.8 h vs. 2.5 h; P < .0001) were seen. There was no significant difference in the amount of anesthetic solution needed, in the need for a second injection, in the injection pain, in pain during treatment, or in postoperative analgesia. In both groups, no complications were seen. CONCLUSIONS: To minimize the epinephrine-induced side effects, 4% articaine without epinephrine is a suitable anesthetic agent for dental extractions in the mandible after inferior alveolar nerve block anesthesia. There could be less postoperative discomfort due to the shorter duration of anesthesia without increased postoperative pain. PMID- 22676932 TI - The diagnostic and surgical management of a multifocal calcifiyng epithelial odontogenic tumor in the mandible and maxilla associated with a squamous odontogenic tumor: first reported case in the literature. AB - The calcifiyng epithelial odontogenic tumor (CEOT) and the squamous odontogenic tumor (SOT) are rare and benign odontogenic tumors that affect the jaw. This article describes the diagnostic and surgical management of a multifocal CEOT in the mandible and maxilla associated with an SOT. This case is the first to demonstrate that there may be a multifocal variant of CEOT associated with an SOT that has not been previously recognized. Clinical, radiographic, and histologic signs are reported. Treatment modality, oral rehabilitation, and long-term follow up are shown. Because of the rarity of this kind of simultaneous pathologic association, it is of paramount, and indeed obvious, importance to prospective reviewers that published reports are produced meticulously, including all clinically, radiographically, and histologically relevant data. PMID- 22676933 TI - [Stenotrophomonas maltophilia endocarditis of bicuspid aortic valve]. PMID- 22676934 TI - Diuretics and ultrafiltration in acute decompensated heart failure. AB - Congestion and volume overload are the hallmarks of acute decompensated heart failure (ADHF), and loop diuretics have historically been the cornerstone of treatment. The demonstrated efficacy of loop diuretics in managing congestion is balanced by the recognized limitations of diuretic resistance, neurohormonal activation, and worsening renal function. However, the recently published DOSE (Diuretic Optimization Strategies Evaluation) trial suggests that previous concerns about the safety of high-dose diuretics may not be valid. There has been a growing interest in alternative strategies to manage volume retention in ADHF with improved efficacy and safety profiles. Peripheral venovenous ultrafiltration (UF) represents a potentially promising approach to volume management in ADHF. Small studies suggest that UF may allow for more effective fluid removal compared with diuretics, with improved quality of life and reduced rehospitalization rates. However, further investigation is needed to completely define the role of UF in patients with ADHF. This review summarizes available data on the use of both diuretics and UF in ADHF patients and identifies challenges and unresolved questions for each approach. PMID- 22676935 TI - A policy for science. AB - Policy and science often interact. Typically, we think of policymakers looking to scientists for advice on issues informed by science. We may appreciate less the opposite look: where people outside science inform policies that affect the conduct of science. In clinical medicine, we are forced to make decisions about practices for which there is insufficient, inadequate evidence to know whether they improve clinical outcomes, yet the health care system may not be structured to rapidly generate needed evidence. For example, when the Centers for Medicare and Medicaid Services noted insufficient evidence to support routine use of computed tomography angiography and they called for a national commitment to completion of randomized trials, their call ran into substantial opposition. I use the computed tomography angiography story to illustrate how we might consider a "policy for science" in which stakeholders would band together to identify evidence gaps and to use their influence to promote the efficient design, implementation, and completion of high-quality randomized trials. Such a policy for science could create a culture that incentivizes and invigorates the rapid generation of evidence, ultimately engaging all clinicians, all patients, and indeed all stakeholders into the scientific enterprise. PMID- 22676936 TI - Approaches for a policy for science. PMID- 22676937 TI - Post-conditioning reduces infarct size and edema in patients with ST-segment elevation myocardial infarction. AB - OBJECTIVES: This study aimed to determine whether post-conditioning at the time of percutaneous coronary intervention could reduce reperfusion-induced myocardial edema in patients with acute ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Myocardial edema is a reperfusion injury with potentially severe consequences. Post-conditioning is a cardioprotective therapy that reduces infarct size after reperfusion, but no previous studies have analyzed the impact of this strategy on reperfusion-induced myocardial edema in humans. METHODS: Fifty patients with STEMI were randomly assigned to either a control or post conditioned group. Cardiac magnetic resonance imaging was performed within 48 to 72 h after admission. Myocardial edema was measured by T2-weighted sequences, and infarct size was determined by late gadolinium enhancement sequences and creatine kinase release. RESULTS: The post-conditioned and control groups were similar with respect to ischemia time, the size of the area at risk, and the ejection fraction before percutaneous coronary intervention. As expected, post conditioning was associated with smaller infarct size (13 +/- 7 g/m(2) vs. 21 +/- 14 g/m(2); p = 0.01) and creatine kinase peak serum level (median [interquartile range]: 1,695 [1,118 to 3,692] IU/l vs. 3,505 [2,307 to 4,929] IU/l; p = 0.003). At reperfusion, the extent of myocardial edema was significantly reduced in the post-conditioned group as compared with the control group (23 +/- 16 g/m(2) vs. 34 +/- 18 g/m(2); p = 0.03); the relative increase in T2W signal intensity was also significantly lower (p = 0.02). This protective effect was confirmed after adjustment for the size of the area at risk. CONCLUSIONS: This randomized study demonstrated that post-conditioning reduced infarct size and edema in patients with reperfused STEMI. PMID- 22676938 TI - Cyclic adenosine monophosphate phosphodiesterase type 4 protects against atrial arrhythmias. AB - OBJECTIVES: This study was designed to examine whether a cyclic adenosine monophosphate (cAMP) phosphodiesterase (PDE), PDE4, is expressed in human atrium and contributes to the control of electrical stability. BACKGROUND: Atrial fibrillation is accompanied by a profound remodeling of membrane receptors and alterations in cAMP-dependent regulation of Ca(2+) handling. Being responsible for cAMP hydrolysis, PDEs are likely to play a role in this setting. In the rodent heart, PDE4 contributes up to 60% of total cAMP-hydrolytic activity. However, its role in the human heart remains controversial. METHODS: L-type Ca(2+) current and spontaneous Ca(2+) release were recorded in isolated human atrial myocytes. Intracellular cAMP was measured by live cell imaging using a fluorescence resonance energy transfer-based sensor. Contractile force and arrhythmias were recorded in human atrial trabeculae. PDE activity was measured in human atrial tissue from patients in sinus rhythm and permanent atrial fibrillation. RESULTS: PDE4 is expressed in human atrial myocytes and accounts for approximately 15% of total PDE activity. PDE4D represents the major PDE4 subtype. PDE4 inhibition increased intracellular cAMP and L-type Ca(2+) current and dramatically delayed their decay after a brief beta-adrenergic stimulation. PDE4 inhibition also increased the frequency of spontaneous Ca(2+) release at baseline, as well as the contractile response and the incidence of arrhythmias in human atrial strips during beta-adrenergic stimulation. Total PDE activity decreased with age, and the relative PDE4 activity was lower in patients with permanent atrial fibrillation than in age-matched sinus rhythm controls. CONCLUSIONS: PDE4 is critical in controlling cAMP levels and thereby Ca(2+) influx and release in human atrial muscle, hence limiting the susceptibility to arrhythmias. PMID- 22676939 TI - Phosphodiesterase-4 activity: a critical modulator of atrial contractility and arrhythmogenesis. PMID- 22676940 TI - Electrophysiologic remodeling of the left ventricle in pressure overload-induced right ventricular failure. AB - OBJECTIVES: The purpose of this study was to analyze the electrophysiologic remodeling of the atrophic left ventricle (LV) in right ventricular (RV) failure (RVF) after RV pressure overload. BACKGROUND: The LV in pressure-induced RVF develops dysfunction, reduction in mass, and altered gene expression, due to atrophic remodeling. LV atrophy is associated with electrophysiologic remodeling. METHODS: We conducted epicardial mapping in Langendorff-perfused hearts, patch clamp studies, gene expression studies, and protein level studies of the LV in rats with pressure-induced RVF (monocrotaline [MCT] injection, n = 25; controls with saline injection, n = 18). We also performed epicardial mapping of the LV in patients with RVF after chronic thromboembolic pulmonary hypertension (CTEPH) (RVF, n = 10; no RVF, n = 16). RESULTS: The LV of rats with MCT-induced RVF exhibited electrophysiologic remodeling: longer action potentials (APs) at 90% repolarization and effective refractory periods (ERPs) (60 +/- 1 ms vs. 44 +/- 1 ms; p < 0.001), and slower longitudinal conduction velocity (62 +/- 2 cm/s vs. 70 +/- 1 cm/s; p = 0.003). AP/ERP prolongation agreed with reduced Kcnip2 expression, which encodes the repolarizing potassium channel subunit KChIP2 (0.07 +/- 0.01 vs. 0.11 +/- 0.02; p < 0.05). Conduction slowing was not explained by impaired impulse formation, as AP maximum upstroke velocity, whole-cell sodium current magnitude/properties, and mRNA levels of Scn5a were unaltered. Instead, impulse transmission in RVF was hampered by reduction in cell length (111.6 +/- 0.7 MUm vs. 122.0 +/- 0.4 MUm; p = 0.02) and width (21.9 +/- 0.2 MUm vs. 25.3 +/- 0.3 MUm; p = 0.002), and impaired cell-to-cell impulse transmission (24% reduction in Connexin-43 levels). The LV of patients with CTEPH with RVF also exhibited ERP prolongation (306 +/- 8 ms vs. 268 +/- 5 ms; p = 0.001) and conduction slowing (53 +/- 3 cm/s vs. 64 +/- 3 cm/s; p = 0.005). CONCLUSIONS: Pressure-induced RVF is associated with electrophysiologic remodeling of the atrophic LV. PMID- 22676941 TI - Pulmonary hypertension: a stage for ventricular interdependence? PMID- 22676943 TI - Multimodality characterization of interatrial cyst. PMID- 22676944 TI - Association between leukocyte telomere length and drug-eluting stent strut coverage by optical coherence tomography. PMID- 22676945 TI - Renal failure following ventricular assist device placement. PMID- 22676942 TI - Autonomic and hemodynamic origins of pre-hypertension: central role of heredity. AB - OBJECTIVES: The purpose of this study is to better understand the origins and progression of pre-hypertension. BACKGROUND: Pre-hypertension is a risk factor for progression to hypertension, cardiovascular disease, and increased mortality. We used a cross-sectional twin study design to examine the role of heredity in likely pathophysiological events (autonomic or hemodynamic) in pre-hypertension. METHODS: Eight hundred twelve individuals (337 normotensive, 340 pre hypertensive, 135 hypertensive) were evaluated in a sample of twin pairs, their siblings, and other family members. They underwent noninvasive hemodynamic, autonomic, and biochemical testing, as well as estimates of trait heritability (the percentage of trait variance accounted for by heredity) and pleiotropy (the genetic covariance or shared genetic determination of traits) by variance components. RESULTS: In the hemodynamic realm, an elevation of cardiac contractility prompted increased stroke volume, in turn increasing cardiac output, which elevated blood pressure into the pre-hypertension range. Autonomic monitoring detected an elevation of norepinephrine secretion plus a decline in cardiac parasympathetic tone. Twin pair variance components documented substantial heritability as well as joint genetic determination for blood pressure and the contributory autonomic and hemodynamic traits. Genetic variation at a pathway locus also indicated pleiotropic effects on contractility and blood pressure. CONCLUSIONS: Elevated blood pressure in pre-hypertension results from increased cardiac output, driven by contractility as well as heart rate, which may reflect both diminished parasympathetic and increased sympathetic tone. In the face of increased cardiac output, systemic vascular resistance fails to decline homeostatically. Such traits display substantial heritability and shared genetic determination, although by loci not yet elucidated. These findings clarify the role of heredity in the origin of pre-hypertension and its autonomic and hemodynamic pathogenesis. The results also establish pathways that suggest new therapeutic targets for pre-hypertension, or approaches to its prevention. PMID- 22676947 TI - Erosion of an implantable cardioverter-defibrillator. PMID- 22676949 TI - Editorial comment. PMID- 22676948 TI - Serous-lined unidirectional valve for construction of continent cutaneous urinary reservoir: the test of time. AB - OBJECTIVE: To assess the long-term outcome of using the serous-lined extramural tunnel technique for construction of continent-cutaneous urinary reservoir in an objective way. METHODS: Cases that were operated until the end of 2003 and were eligible for evaluation at the time of the study were included. Continence, upper tract status, and complications were the targets of evaluation. Clear definition of continence was used, and biochemical kidney function profile was assessed with calculation of estimated glomerular filtration rate (eGFR) as a measure of the overall renal function in addition to the standard radiological assessment tools. A modified Clavien scale was followed for grading of complications. RESULTS: After a median of 121.3 months, the final continence rate was 91.1%. Maintained upper tract status was in almost 96.6% of cases and stricture of ureterointestinal anastomosis (UIA) was diagnosed in 3 renal units, and ureteral reflux was diagnosed in 24 renal units. Biochemical kidney function profile showed mean percent reduction of total eGFR to be 14.2%, and 3 patients had >=50% reduction of total eGFR. On the Clavien scale, low-grade complications (GI-II) occurred in 30 patients (33%) and high-grade complications (>=GIII) occurred in 36 patients (40%). Stoma complications were the most frequent complications. At last follow-up, 42 patients (47%) were free of complications. CONCLUSION: The serous-lined extramural valve is an efficient technique for maintaining unidirectional flow. Over a decade, good functional outcome of the cutaneous reservoir has been evident. However, with a clear definition of continence and objective assessment of the outcome, at least one third of patients will have high-grade complications, with excellent reintervention outcome maintaining efficacy of the technique. PMID- 22676951 TI - Plausible mechanism of melamine-related urinary calculi formation in children: a model description. AB - OBJECTIVE: To explore melamine-related urinary calculi (MRUC) formation mechanism. MATERIALS AND METHODS: Twenty-four MRUC and 19 adult urinary stones (serving as controls) were included. Stone calcium, uric acid, creatinine, creatine, melamine, and cyanuric acid levels were measured quantitatively using flame atomic absorption spectrum and high-performance liquid chromatography, respectively. The structure of extractions from MRUC and controls, artificial melamine-cyanurate assemblies, chromatographic-grade uric acid, creatine, and creatinine were investigated by transmission electron microscope. RESULTS: Creatinine and creatine levels in MRUC were significant higher than those in controls (P = .000., 008). There were positive correlations between MRUC creatinine level and creatine and uric acid levels (r = .854, 0.846, P = .002, 001). However, no relationship was found between MRUC-children's blood biochemical indexes and stone indexes (P > .05). Compared with noncalcium oxalate containing MRUC, calcium oxalate-containing MRUC had more melamine and cyanuric acid but without significance (P = .497). No relationship was found between MRUC calcium level and melamine and cyanurate levels (P = .481). Networks only observed in extractions from MRUC core area were very similar to those in artificial melamine-cyanurate assemblies. The single molecule size of creatine, creatinine, and uric acid was less than the mesh observed both in MRUC and artificial melamine-cyanurate assemblies. CONCLUSION: This study primarily illustrates existence of networks in MRUC. Smaller molecules in urine, especially acidic molecules, are probably trapped in the mesh within renal tubule provided by melamine-cyanurate assemblies networks based on its molecule sievelike effect and alkaline nature, which induces nucleation in MRUC formation. PMID- 22676952 TI - Comparison of the effects of four alpha1-adrenoceptor antagonists on ejaculatory function in rats. AB - OBJECTIVE: To compare the effects of four alpha(1)-adrenoceptor (AR) subtype selective antagonists on ejaculatory function in rats to investigate whether the differences in their modes of action-based on their selectivities for the alpha(1A)-AR subtype-would be related to the prevalence of ejaculation disorder (EjD). METHODS: The effects of alpha(1)-AR antagonists on noradrenaline-induced contractions were studied in rat isolated seminal vesicles, vas deferens, bladder trigone, and prostate. Male rats were given alpha(1)-AR antagonists orally and, 1 hour after the drug administration they were cohoused in pairs for 1 hour with untreated female rats certified to be in estrus. The number of copulatory plugs (NP) present after mating was measured as a marker of EjD. Drug effects on ejaculatory function (ie, on NP) were compared with those on the prostatic urethra (ie, phenylephrine-induced increase in intraurethral pressure [IUP]). RESULTS: All alpha(1)-AR antagonists concentration-dependently inhibited noradrenaline-induced contraction in all 4 tissues, and there were no differences in the rank order of potencies (tamsulosin > silodosin > alfuzosin > naftopidil) among the tissues. All alpha(1)-AR antagonists dose-dependently decreased NP and inhibited the phenylephrine-induced increase in IUP. There was little difference in the dose ratio ID(50) value (dose required to produce 50% inhibition) for NP/ID(50) value for IUP response among the four drugs. Drug potencies associated NP and IUP correlated closely with affinities for the human alpha(1A)-AR. CONCLUSION: alpha(1)-AR antagonists cause EjD as a class effect that depends on affinity for alpha(1A)-AR. Differences in alpha(1A)-AR selectivity would be unlikely to be related to the incidence of EjD. PMID- 22676953 TI - Sunitinib malate provides activity against murine bladder tumor growth and invasion in a preclinical orthotopic model. AB - OBJECTIVE: To evaluate the effects of sunitinib on localized bladder cancer in a mouse orthotopic bladder tumor model. METHODS: We used an established orthotopic mouse bladder cancer model in syngeneic C3H/He mice. Treatment doses of 40 mg/kg of sunitinib or placebo sterile saline were administrated daily by oral gavage. Tumor volume, intratumoral perfusion, and in vivo vascular endothelial growth factor receptor-2 expression were measured using a targeted contrast-enhanced micro-ultrasound imaging system. The findings were correlated with the total bladder weight, tumor stage, and survival. The effects of sunitinib malate on angiogenesis and cellular proliferation were measured by immunostaining of CD31 and Ki-67. RESULTS: Significant inhibition of tumor growth was seen after sunitinib treatment compared with the control. The incidence of extravesical extension of the bladder tumor and hydroureter in the sunitinib-treated group (30% and 20%, respectively) was lower than the incidence in the control group (66.7% and 55.6%, respectively). Sunitinib therapy prolonged the survival in mice, with statistical significance (log-rank test, P = .03). On targeted contrast-enhanced micro-ultrasound imaging, in vivo vascular endothelial growth factor receptor-2 expression was reduced in the sunitinib group and correlated with a decrease in microvessel density. CONCLUSION: The results of our study have demonstrated the antitumor effects of sunitinib in the mouse localized bladder cancer model. Sunitinib inhibited the growth of bladder tumors and prolonged survival. Given that almost 30% of cases in our treatment arm developed extravesical disease, sunitinib might be suited as a part of a multimodal treatment regimen for bladder cancer. PMID- 22676954 TI - Increasing magnitude counts more: asymmetrical processing of ordinality in 4 month-old infants. AB - While infants' ability to discriminate quantities has been extensively studied, showing that this competence is present even in neonates, the ability to compute ordinal relations between magnitudes has received much less attention. Here we show that the ability to represent ordinal information embedded in size-based sequences is apparent at 4months of age, provided that magnitude changes involve increasing relations. Infants in Experiments 1A and 1B discriminated changes in ordinal relations after habituation to ascending sequences, but did not show evidence of discrimination after habituation to descending sequences. In Experiment 2 we replicated this asymmetry in magnitude discrimination even when additional cues known to boost ordinal competence were provided. The presence of an asymmetry between ascending vs. descending order during infancy suggests a developmental continuity in the underlying code used to represent magnitude, whereby the reported addition advantage in children and adults' arithmetic performance emerges. PMID- 22676955 TI - Evaluations of hydrologic risk factors for canine leptospirosis: 94 cases (2002 2009). AB - Hydrologic and soil-hydrologic variables were evaluated retrospectively as potential risk factors for canine leptospirosis in Kansas and Nebraska using Geographic Information Systems (GIS). The sample included 94 positive and 185 negative dogs for leptospirosis predominantly based on PCR test for leptospires in urine. Hydrologic variables for the region were derived from National Hydrographic Dataset, National Flood Hazard Layer, National Wetlands Inventory; and soil-hydrologic variables from Soil Survey Geographic Database around geocoded addresses of case/control locations. Multivariable logistic models were used to determine association between hydrologic and soil-hydrologic variables and test status. Distance from water features (OR=0.82; 95% CI=0.79, 0.86), hydrologic density (OR=2.80; 95% CI=1.58, 4.96) and frequently flooded areas (OR=4.05; 95% CI=2.17, 7.55) within 2500 m surrounding case/control locations were significant risk factors for canine leptospirosis. Vaccination for dogs that live closer to water features, landscapes dominated by water features and frequent floods should be considered for leptospirosis prevention. PMID- 22676957 TI - Intradural endoscope-assisted anterior clinoidectomy: a cadaveric study. AB - OBJECTIVE: The anterior clinoid process (ACP) is critically related to the clinoidal portion of the internal carotid artery (ICA). The deep location of the ACP makes treatment of vascular and neoplastic lesions related to the ACP challenging. Removal of the ACP is advocated to facilitate treatment of such lesions. However injury to the clinoidal ICA remains a potential and dreadful complication of ACP removal. The aim of this study was to demonstrate an endoscopic assisted technique to perform intradural removal of the ACP via a pterional approach with continuous visualization of the clinoidal ICA. METHODS: Sixteen bilateral pterional dissections were performed in 8 glutaraldehyde embalmed, colored silicone injected, adult cadaveric heads. Using a standard pterional approach, we performed drilling of the ACP in 2 stages. Stage 1 consisted of extradural microscopic removal of the sphenoid ridge so as to gain access to the origin of the ACP. Stage 2, the endoscopic stage, consisted of intradural endoscopic removal of the ACP and mobilization of the clinoidal segment of the ICA. We used 2.7 mm, 0 degrees and 30 degrees angled endoscopes. RESULTS: In all the specimens we were able to remove the ACP while at the same time continuously visualizing the clinoidal ICA. The exposure of the clinoidal ICA and of adjoining neuro-vascular structures including the intracranial optic nerve was excellent and was accomplished with minimal frontal lobe retraction. Mobilization of the clinoidal ICA led to unhindered exposure of the parasellar region. CONCLUSIONS: Endoscopic assisted ACP removal with continuous ICA visualization was feasible in our model. Continuous visualization of the clinoidal ICA should theoretically decrease the risk of inadvertent ICA injuries. Clinical studies to validate this laboratory study are necessary. PMID- 22676956 TI - Clinical differences between acute CVST and non-thrombotic CVSS. AB - BACKGROUND: Cerebral venous sinus thrombosis (CVST) is a rare stroke subtype, which has many overlapping symptoms with non-thrombotic cerebral venous sinus stenosis (CVSS) in the acute phase. Despite these similarities, their therapeutic regimens and outcomes are entirely different, and treatment delay is life threatening. This study aims to address their clinical differences to help promote proper patient care. METHODS: 34 cases of CVST and 34 cases of non thrombotic CVSS diagnosed with digital subtraction angiography (DSA) in the acute phase (symptoms onset within 7days) were consecutively enrolled in this prospective non-randomized and controlled study. Differences between CVST and CVSS in their clinical manifestation, plasma biomarkers, and MR or DSA imaging were compared. RESULTS: CVST and CVSS overlap in many ways, but differ in their respective medical histories and neurological deficits. However, 20.6% of CVST and 64.7% of CVSS occur without a definitive medical history, and 70.6% of CVST and 64.7% of CVSS occur without focal neurologic deficits. In the acute phase of CVST, d-dimer and fibrinogen are found to be abnormally elevated in 94.1% and 73.5% of cases, respectively. In the CVSS group, d-dimer and fibrinogen are only elevated in 17.6% and 5.9% of cases, respectively (binary logistic regressions test, all P<0.001). In the CVST group, the predominant features in MRI/MRV and DSA imaging include local brain lesions, flow void signal loss, non visualization, and a local filling defect sign at the involved sinus. Conversely, in the CVSS group, imaging revealed symmetrically small bilateral ventricles and the spread of cerebral edema in MRI/MRV. DSA imaging in the CVSS group revealed external compression and a narrow sinus with disproportionate venous engorgement. Despite these findings, positive imaging only appears in a minority of patients in the two groups during the acute phase (Table 4). CONCLUSIONS: DSA may be beneficial to diagnose CVST in ambiguous patients suspected to have either CVST or CVSS. Clinically useful biomarkers (d-dimer and fibrinogen) may predict CVST in the emergency room in the ambiguous patients with or without equivocal MRI/MRV imaging. PMID- 22676958 TI - Abnormal sympathetic hyper-reactivity in patients with myasthenia gravis: a prospective study. AB - INTRODUCTION: Patients with myasthenia gravis, especially those in crises, are not infrequently observed to demonstrate wide fluctuation in heart rate and blood pressure. OBJECTIVE: This study was conducted to assess autonomic function in patients with myasthenia gravis. METHODS: Patients with myasthenia gravis diagnosed on the basis of typical clinical details, edrophonium or neostigmine test, decremental response on repetitive nerve stimulation testing and anti acetyl choline receptor antibody testing, were compared with age and gender matched controls. Apart from detailed clinical evaluation, all subjects underwent tests of autonomic function, viz. heart rate and blood pressure response on orthostatic tests and isometric handgrip test, Valsalva maneuver, R-R interval variation (RRIV) and the sympathetic skin response (SSR). Results were compared with those in the control group using repeated measures ANOVA and the paired t test. RESULTS: Sixty-four patients (27 males, 37 females) with a mean age of 40.5 +/- 17 years) with myasthenia gravis of an average 3 +/- 4 years duration, and 241 normal controls were enrolled. On the orthostatic tests, patients showed rise in heart rate, systolic and diastolic blood pressure, as did controls, however, the rate and the duration of rise was significantly higher than in the controls (p < 0.01). Similar difference between patients and controls, in rate of rise of these parameters was observed on the isometric hand grip test. No significant difference was observed between the two groups on tests of parasympathetic function (Valsalva ratio, RRIV). These effects could also partially be due to pyridostigmine, which all patients were receiving. CONCLUSION: This study suggests sympathetic hyper-reactivity in patients with myasthenia gravis, which could be responsible for serious hemodynamic instability in patients in crisis. PMID- 22676959 TI - Turcot's syndrome associated with intestinal non-Hodgkin's lymphoma: case report and review of literature. AB - A 15-year-old boy was admitted with the diagnosis of colonic polyposis, and during a 2-year follow-up, he underwent operation for right parieto-occipital anaplastic astrocytoma, left-side colonic non-Hodgkin lymphoma (NHL) and cerebella glioblastoma which were all confirmed by histology. Although cases of Turcot's syndrome (TS) (colonic polyposis and primary brain tumour occurring in the same patient) have been previously described, association with haematological malignancy is rare. We hereby report such a case with TS. PMID- 22676960 TI - Functional characterization of UCP1 in mammalian HEK293 cells excludes mitochondrial uncoupling artefacts and reveals no contribution to basal proton leak. AB - Mechanistic studies on uncoupling proteins (UCPs) not only are important to identify their cellular function but also are pivotal to identify potential drug targets to manipulate mitochondrial energy transduction. So far, functional and comparative studies of uncoupling proteins in their native environment are hampered by different mitochondrial, cellular and genetic backgrounds. Artificial systems such as yeast ectopically expressing UCPs or liposomes with reconstituted UCPs were employed to address crucial mechanistic questions but these systems also produced inconsistencies with results from native mitochondria. We here introduce a novel mammalian cell culture system (Human Embryonic Kidney 293 - HEK293) to study UCP1 function. Stably transfected HEK293 cell lines were derived that contain mouse UCP1 at concentrations comparable to tissue mitochondria. In this cell-based test system UCP1 displays native functional behaviour as it can be activated with fatty acids (palmitate) and inhibited with purine nucleotides guanosine-diphosphate (GDP). The catalytic centre activity of the UCP1 homodimer in HEK293 is comparable to activities in brown adipose tissue supporting functionality of UCP1. Importantly, at higher protein levels than in yeast mitochondria, UCP1 in HEK293 cell mitochondria is fully inhibitable and does not contribute to basal proton conductance, thereby emphasizing the requirement of UCP1 activation for therapeutic purposes. These findings and resulting analysis on UCP1 characteristics demonstrate that the mammalian HEK293 cell system is suitable for mechanistic and comparative functional studies on UCPs and provides a non-confounding mitochondrial, cellular and genetic background. PMID- 22676961 TI - Nonverifiable research publications among applicants to an academic trauma and surgical critical care fellowship program. AB - BACKGROUND: The purpose of this study was to determine the incidence and predictors of nonverifiable research publications among applicants to a trauma and surgical critical care fellowship program. STUDY DESIGN: All complete applications submitted to our trauma and surgical critical care fellowship program were prospectively collected for 4 application cycles (2009 to 2012). All publications listed by applicants were tabulated and underwent verification using MEDLINE and direct journal search with verification by a team of professional health sciences librarians. Demographics and academic criteria were compared between applicants with nonverifiable and verifiable publications. RESULTS: A total of 100 applicants reported 301 publications. Of those, 20 applicants (20%) listed 32 papers (11%) that could not be verified. These applicants comprised 30% of those with 1 or more peer-reviewed publications. There were no significant differences in sex (male, 55% nonverifiable vs 60% verifiable, p = 0.684) or age (34.3 +/- 6.6 years vs 34.2 +/- 5.0 years, p = 0.963). There were no differences with regard to citizenship status (foreign medical graduates, 20% nonverifiable vs 28% verifiable, p = 0.495). Applicants with nonverified publications were less likely to be in the military (0% vs 14%, p = 0.079), more likely to have presented their work at surgical meetings (80% vs 58%, p = 0.064), and to be individuals with 3 or more peer-reviewed publications (55% vs 25%, p = 0.009). CONCLUSIONS: In this analysis of academic integrity, one-fifth of all applicants applying to a trauma and surgical critical care fellowship program and 30% of those with 1 or more peer-reviewed publications had nonverifiable publications listed in their curricula vitae. These applicants were less likely to be in the military, more likely to have presented their work at surgical meetings and to have 3 or more peer-reviewed publications. PMID- 22676962 TI - Factors affecting selection of operative approach and subsequent short-term outcomes after anatomic resection for lung cancer. AB - BACKGROUND: Previous studies evaluating video-assisted thoracoscopic surgery (VATS) for lung cancer are single-institution series, suffer from small sample size, or use administrative or self-reported databases. Using a multi institutional, standardized, and audited surgical outcomes database, our objectives were to examine preoperative factors associated with undergoing VATS vs open resection and assess subsequent perioperative outcomes. STUDY DESIGN: The American College of Surgeons National Surgical Quality Improvement Program Participant Use File was used to identify patients who underwent anatomic resection (eg, segmentectomy, lobectomy, and bi-lobectomy) for primary lung cancer (2005 to 2010). Multiple logistic regression models, including propensity scores, were developed to assess preoperative factors associated with undergoing VATS and the risk-adjusted association between operative approach and 30-day outcomes. RESULTS: Of 2,353 patients undergoing resection, 74% underwent open thoracotomy (OT) and 26% underwent VATS. After regression for confounders, factors associated with undergoing a VATS were patient age older than 75 years (odds ratio [OR] = 1.41; 95% CI, 1.05-1.90), Hispanic ethnicity (OR = 2.52; 95% CI, 1.69-3.77), and cardiothoracic surgery training (OR = 1.68; 95% CI, 1.37 2.07). Patients undergoing OT had a higher likelihood of any adverse event developing (24% vs 14%; OR = 1.76; 95% CI, 1.35-2.29), specifically pneumonia and sepsis/septic shock. Median length of stay was significantly longer in the OT group (7 vs 4 days; p < 0.001). Mortality was not significantly different for VATS vs OT after regression for confounders. CONCLUSIONS: In addition to patient factors, surgeon training can play a role in determining the operative approach offered to patients. Patients selected for VATS had a lower 30-day morbidity and shorter length of stay compared with OT anatomic resection for primary lung cancer. PMID- 22676964 TI - Dynamic modulation of emotional processing. AB - Recent findings suggest the processing of emotional stimuli is prioritized compared to neutral stimuli; however, it is not necessarily automatic and depends on several modulating factors. The current paper highlights three major factors that affect the reactions to emotional stimuli: (i) stimulus properties, (ii) task demands and attention, and (iii) individual characteristics. The evidence reviewed here suggests that individual characteristics shape the structure, function and connectivity within a neural network that is involved in the reactions to emotional stimuli. This neural network includes regions related to emotion and attention, in line with evidence for reciprocal connections between these two processes. Activation in this network further depends on the emotional value of a certain item, as well as physical features of the stimulus. This integrative view can lead to better understanding of the underlying mechanisms of emotional reactions, as well as better therapeutic approaches. PMID- 22676963 TI - Surgical malpractice in the United States, 1990-2006. AB - BACKGROUND: Information about national trends and predictors of malpractice payments can constructively add to the hotly debated topic of medical malpractice. We sought to evaluate predictors of surgical malpractice payments and to explore national trends. STUDY DESIGN: Retrospective analysis of surgery related malpractice payments using the National Practitioner Data Bank from 1990 to 2006. Payments were adjusted to 2006 dollars. We evaluated predictors of payment size and large payments (defined as those >$1 million). Statutory law in the states demonstrating significant predictive values was analyzed. RESULTS: In total, 58,518 surgical malpractice payments met inclusion criteria. Patients were predominantly female (62%) and inpatient (63%), with a mean age of 42 years. The number of payments decreased and payment sums increased during the study period. Median payment was $132,915 (95th percentile $983,263). Claims most frequently cited improper performance (42%). Patient outcomes were the strongest predictor of both payment size and likelihood of a large payment. Children younger than 10 years old were 70% more likely to receive a large payment (p = 0.005); and patients older than 70 years were 80% less likely (p < 0.0005). Large variations across states were seen for both payment size and likelihood of large payment. The likelihood of reaching out-of-court settlement did not appear to be correlated with known factors. CONCLUSIONS: Nationwide, surgical malpractice claims show rising payment amounts. Patient outcomes are the strongest predictor of payment size. Considerable variation in payment size between states suggests a profound impact from local legal environments. PMID- 22676965 TI - Hemodynamic and autonomic modifications during sleep stages in young hypotensive women. AB - This study examined cardiovascular activity and autonomic involvement during sleep in essential hypotension. We compared young female hypotensives and normotensives using ambulatory blood pressure monitoring, impedance cardiography, and frequency-domain analysis of heart rate variability during a night of polysomnographic recording. Hypotensives, as compared to normotensives, exhibited lower blood pressure, reduced myocardial contractility and reduced sympathovagal balance across the whole night. Both groups exhibited a reduction in cardiovascular involvement from wake to sleep with similar cardiovascular activity during wake and REM. No group difference was observed in sleep architecture suggesting similar sleeping quality in hypotensives and normotensives. The lower blood pressure and reduced myocardial contractility associated with a lower sympathovagal balance in hypotensives, as compared to normotensives, suggest a night-time hypoactivation of the cardiovascular system supporting the hypothesis of impairment in autonomic control in essential hypotension. PMID- 22676967 TI - Interpreting estimates of heritability--a note on the twin decomposition. AB - While most outcomes may in part be genetically mediated, quantifying genetic heritability is a different matter. To explore data on twins and decompose the variation is a classical method to determine whether variation in outcomes, e.g. IQ or schooling, originate from genetic endowments or environmental factors. Despite some criticism, the model is still widely used. The critique is generally related to how estimates of heritability may encompass environmental mediation. This aspect is sometimes left implicit by authors even though its relevance for the interpretation is potentially profound. This short note is an appeal for clarity from authors when interpreting the magnitude of heritability estimates. It is demonstrated how disregarding existing theoretical contributions can easily lead to unnecessary misinterpretations and/or controversies. The key arguments are relevant also for estimates based on data of adopted children or from modern molecular genetics research. PMID- 22676966 TI - Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder. AB - The N-methyl-d-aspartate (NMDA) receptor antagonist ketamine has rapid antidepressant effects in treatment-resistant major depressive disorder (MDD). In rats, ketamine selectively increased electroencephalogram (EEG) slow wave activity (SWA) during non-rapid eye movement (REM) sleep and altered central brain-derived neurotrophic factor (BDNF) expression. Taken together, these findings suggest that higher SWA and BDNF levels may respectively represent electrophysiological and molecular correlates of mood improvement following ketamine treatment. This study investigated the acute effects of a single ketamine infusion on depressive symptoms, EEG SWA, individual slow wave parameters (surrogate markers of central synaptic plasticity) and plasma BDNF (a peripheral marker of plasticity) in 30 patients with treatment-resistant MDD. Montgomery-Asberg Depression Rating Scale scores rapidly decreased following ketamine. Compared to baseline, BDNF levels and early sleep SWA (during the first non-REM episode) increased after ketamine. The occurrence of high amplitude waves increased during early sleep, accompanied by an increase in slow wave slope, consistent with increased synaptic strength. Changes in BDNF levels were proportional to changes in EEG parameters. Intriguingly, this link was present only in patients who responded to ketamine treatment, suggesting that enhanced synaptic plasticity - as reflected by increased SWA, individual slow wave parameters and plasma BDNF - is part of the physiological mechanism underlying the rapid antidepressant effects of NMDA antagonists. Further studies are required to confirm the link found here between behavioural and synaptic changes, as well as to test the reliability of these central and peripheral biomarkers of rapid antidepressant response. PMID- 22676968 TI - Negotiating access: social barriers to purchasing syringes at pharmacies in Tijuana, Mexico. AB - BACKGROUND: One common public health response to the emergence of HIV has been the provision of sterile syringes to people who inject drugs. In Mexico specialized syringe exchanges are rare, and the sale of needles through pharmacies is often the only way people who inject drugs can obtain sterile syringes. However, people who inject drugs in Tijuana, Mexico report considerable social barriers to successfully purchasing syringes at pharmacies. METHODS: Between October 2008 and March 2009 we conducted seven in-depth focus groups with 47 people who inject drugs in Tijuana, Mexico. Focus group transcripts were analysed using a descriptive and thematic approach rooted in grounded theory. RESULTS: We found that injectors offered a number of explanations for why pharmacies were reluctant to sell them syringes, including fear of police; attitudes toward drug use; fear of stereotypical drug user behaviour such as petty theft, violence, or distressing behaviour; and related fears that an obvious drug using clientele would drive away other customers. Injectors described a range of ways of attempting to re-frame or negotiate interactions with pharmacy staff so that these and related concerns were ameliorated. These included tactics as simple as borrowing cleaner clothing, through to strategies for becoming 'known' to pharmacy staff as an individual rather than as a member of a stigmatized group. CONCLUSION: Increasing the ability of pharmacy staff and people who inject drugs to successfully negotiate syringe sales are highly desirable. Interventions designed to improve this likelihood need to capitalize on existing solutions developed ad hoc by people who inject drugs and pharmacy staff, and should focus on broadening the range of 'identities' which pharmacy staff are able to accept as legitimate customers. Approaches to achieve this end might include sensitizing pharmacy staff to the needs of people who inject drugs; facilitating individual drug users meeting individual pharmacy staff; and working with drug users to reduce behaviours seen as problematic by pharmacy staff. PMID- 22676969 TI - Structural basis for the protective effect of the human prion protein carrying the dominant-negative E219K polymorphism. AB - The most common form of prion disease in humans is sCJD (sporadic Creutzfeldt Jakob disease). The naturally occurring E219K polymorphism in the HuPrP (human prion protein) is considered to protect against sCJD. To gain insight into the structural basis of its protective influence we have determined the NMR structure of recombinant HuPrP (residues 90-231) carrying the E219K polymorphism. The structure of the HuPrP(E219K) protein consists of a disordered N-terminal tail (residues 90-124) and a well-structured C-terminal segment (residues 125-231) containing three alpha-helices and two short antiparallel beta-strands. Comparison of NMR structures of the wild-type and HuPrPs with pathological mutations under identical experimental conditions revealed that, although the global architecture of the protein remains intact, replacement of Glu219 with a lysine residue introduces significant local structural changes. The structural findings of the present study suggest that the protective influence of the E219K polymorphism is due to the alteration of surface charge distribution, in addition to subtle structural rearrangements localized within the epitopes critical for prion conversion. PMID- 22676971 TI - Hierarchical twin-scale inverse opal TiO2 electrodes for dye-sensitized solar cells. AB - We describe the preparation of three-dimensional hierarchical twin-scale inverse opal (ts-IO) electrodes for dye-sensitized solar cells (DSSCs). The ts-IO TiO(2) structure was obtained from a template fabricated via the assembly of mesoscale colloidal particles (40-80 nm in diameter) in the confined geometry of a macroporous IO structure. The photovoltaic properties of ts-IO electrodes were optimized by varying the layer thickness or the size of mesopores in the mesoscale colloidal assembly. Electron transport was investigated using impedance spectroscopy. The result showed that due to the competing effects of recombination and dye adsorption, the maximum efficiency was observed at an electrode thickness of 12 MUm. The electrodes of smaller mesopores diameters yielded the higher photocurrent density due to the decrease in the electron transport resistance at the TiO(2)/dye interface. A maximum efficiency of 6.90% was obtained using an electrode 12 MUm thick and a mesopore diameter of 35 nm. PMID- 22676970 TI - Effect of pre-existing anti-diphtheria toxin antibodies on T cell depletion levels following diphtheria toxin-based recombinant anti-monkey CD3 immunotoxin treatment. AB - Diphtheria toxin (DT)-based anti-CD3 immunotoxins have clinical relevance in numerous applications including autoimmune disease therapies and organ transplantation tolerance protocols. Pre-existing anti-DT antibodies acquired either by vaccination against diphtheria toxin or infections with C. diphtheriae may interfere or inhibit the function of these anti-CD3 immunotoxins. Previously, a full-length anti-rhesus monkey CD3 immunotoxin, FN18-CRM9, was shown to be less effective at depleting circulating T cells in animals with pre-existing anti-DT antibody titers than in animals without antibodies, and subsequent doses were ineffective. In this study, the T cell depletion function of a truncated DT based recombinant anti-monkey CD3 immunotoxin, A-dmDT390-scfbDb (C207), as part of a reduced intensity conditioning regimen prior to hematopoietic cell transplantation, was compared between two groups of monkeys: those with and without pre-existing anti-diphtheria titers. T cell depletion was comparable in both groups of monkeys, and therefore appeared to be unaffected by the presence of moderate levels of pre-existing anti-diphtheria antibodies. PMID- 22676972 TI - HER2-targeted liposomal doxorubicin displays enhanced anti-tumorigenic effects without associated cardiotoxicity. AB - Anthracycline-based regimens are a mainstay of early breast cancer therapy, however their use is limited by cardiac toxicity. The potential for cardiotoxicity is a major consideration in the design and development of combinatorial therapies incorporating anthracyclines and agents that target the HER2-mediated signaling pathway, such as trastuzumab. In this regard, HER2 targeted liposomal doxorubicin was developed to provide clinical benefit by both reducing the cardiotoxicity observed with anthracyclines and enhancing the therapeutic potential of HER2-based therapies that are currently available for HER2-overexpressing cancers. While documenting the enhanced therapeutic potential of HER2-targeted liposomal doxorubicin can be done with existing models, there has been no validated human cardiac cell-based assay system to rigorously assess the cardiotoxicity of anthracyclines. To understand if HER2-targeting of liposomal doxorubicin is possible with a favorable cardiac safety profile, we applied a human stem cell-derived cardiomyocyte platform to evaluate the doxorubicin exposure of human cardiac cells to HER2-targeted liposomal doxorubicin. To the best of our knowledge, this is the first known application of a stem cell-derived system for evaluating preclinical cardiotoxicity of an investigational agent. We demonstrate that HER2-targeted liposomal doxorubicin has little or no uptake into human cardiomyocytes, does not inhibit HER2-mediated signaling, results in little or no evidence of cardiomyocyte cell death or dysfunction, and retains the low penetration into heart tissue of liposomal doxorubicin. Taken together, this data ultimately led to the clinical decision to advance this drug to Phase I clinical testing, which is now ongoing as a single agent in HER2-expressing cancers. PMID- 22676973 TI - Acute alteration of cardiac ECG, action potential, I(Kr) and the human ether-a-go go-related gene (hERG) K+ channel by PCB 126 and PCB 77. AB - Polychlorinated biphenyls (PCBs) have been known as serious persistent organic pollutants (POPs), causing developmental delays and motor dysfunction. We have investigated the effects of two PCB congeners, 3,3',4,4'-tetrachlorobiphenyl (PCB 77) and 3,3',4,4',5-pentachlorobiphenyl (PCB 126) on ECG, action potential, and the rapidly activating delayed rectifier K+ current (I(Kr)) of guinea pigs' hearts, and hERG K+ current expressed in Xenopus oocytes. PCB 126 shortened the corrected QT interval (QTc) of ECG and decreased the action potential duration at 90% (APD(90)), and 50% of repolarization (APD50) (P<0.05) without changing the action potential duration at 20% (APD20). PCB 77 decreased APD20 (P<0.05) without affecting QTc, APD90, and APD50. The PCB 126 increased the I(Kr) in guinea-pig ventricular myocytes held at 36 degrees C and hERG K+ current amplitude at the end of the voltage steps in voltage-dependent mode (P<0.05); however, PCB 77 did not change the hERG K+ current amplitude. The PCB 77 increased the diastolic Ca2+ and decreased Ca2+ transient amplitude (P<0.05), however PCB 126 did not change. The results suggest that PCB 126 shortened the QTc and decreased the APD90 possibly by increasing I(Kr), while PCB 77 decreased the APD20 possibly by other modulation related with intracellular Ca2+. The present data indicate that the environmental toxicants, PCBs, can acutely affect cardiac electrophysiology including ECG, action potential, intracellular Ca2+, and channel activity, resulting in toxic effects on the cardiac function in view of the possible accumulation of the PCBs in human body. PMID- 22676974 TI - Phylogeographic structure, outbreeding depression, and reluctant virgin oviposition in the bean thrips, Caliothrips fasciatus (Pergande) (Thysanoptera: Thripidae), in California. AB - Bean thrips, Caliothrips fasciatus, is native to western North America. Once considered a pest of several crops in its native area, its pest status has waned over recent decades. However, due to its habit of aggregating in the navel of navel oranges, bean thrips remains economically important because some countries importing oranges from California have designated it a quarantine pest. Despite continued propagule pressure, bean thrips has never established outside North America. We examined genetic variation in mitochondrial DNA among Californian populations of C. fasciatus and found that potentially two cryptic species are present (supported by Kimura 2-P distances): a common widespread form B and a rarer form A with a very limited distribution. Form B showed strong phylogeographic structure, with many haplotypes having a limited geographic distribution. Inter-population crossing experiments between three geographically isolated populations of form B resulted in the production of some female offspring, indicating a degree of compatibility between these populations of this haplodiploid species. However, substantial outbreeding depression was also detected. A low frequency of offspring production by hetero-population pairs was evidence of pre-mating isolation, while post-mating isolation was also evident in the elevated mortality of fertilized eggs in successful hetero-population crosses. One surprising finding was the total lack of offspring production by virgin females when isolated individually. However, virgin females did produce sons in the presence of other virgin females. A test for the presence of Wolbachia showed that form B was not infected, but that some populations of the rarer form A were. PMID- 22676975 TI - Risk factors for inguinal hernia in adult male Nigerians: a case control study. AB - BACKGROUND: We sought to evaluate selected risk factors for development of inguinal hernia in adult male Nigerians in a hospital based case control study. The aim was to identify the risks for this condition in our population. This may assist in instituting appropriate preventive measures towards early detection and treatment. METHODS: All male patients aged 18 years and above who presented with primary inguinal hernia at the General Surgical clinic of Ikorodu General Hospital between April 2009 and March 2011 were enrolled into the study as cases. Control subjects were selected randomly from the general out-patient clinic. Participants were interviewed during their first clinic attendance using a standardised questionnaire to record their bio-data and the presence or absence of the risk factors. All study cases had hernia repair and the type of hernia, whether indirect or direct was determined and documented. SPSS version 15.0 was used in the statistical analysis and the risk factors among the cases and controls were compared using univariate and multivariate logistic regression analysis. RESULTS: A total number of 404 male patients were interviewed. Two hundred and two were the cases while the remaining 202 were the controls. Significant risk factors for inguinal hernia were positive family history of inguinal hernia (p < 0.001 and strenuous work activities (p < 0.001). Among the cases, 132 (65.3%) had indirect hernia while the remaining 70 (34.7%) had direct hernia. Positive family history (p = 0.011) and straining during urination or defecation (p = 0.047) were the factors significantly associated with the type of hernia. CONCLUSION: Family history of inguinal hernia and strenuous work activity are the significant risk factors for this condition in our setting. Public health initiatives targeting those at higher risk of hernia development may help early detection and treatment; thereby reducing morbidity and mortality from this condition. PMID- 22676976 TI - Video-assisted thoracoscopic mediastinal lymph node dissection. PMID- 22676977 TI - Lung cancer screening trials: the United States and beyond. PMID- 22676978 TI - Tracheobronchoplasty for the treatment of tracheobronchomalacia. PMID- 22676979 TI - Clinical analysis of concomitant valve replacement and bipolar radiofrequency ablation in 191 patients. AB - OBJECTIVE: The study objective was to evaluate the safety and efficacy of concomitant bipolar radiofrequency ablation and heart valve replacement in patients with rheumatic heart disease and atrial fibrillation. METHODS: A total of 191 patients with rheumatic heart disease and chronic atrial fibrillation underwent valve replacement with concomitant bipolar radiofrequency ablation. There were 78 male and 113 female patients with a mean age of 46.0 +/- 9.1 years and an atrial fibrillation duration of 43.7 +/- 15.4 months. Valve replacement surgery included mitral valve replacement in 121 patients, mitral and aortic valve replacement in 59 patients, mitral and tricuspid valve replacement in 8 patients, and triple valve replacement in 3 patients. All patients received oral antiarrhythmic drugs for 3 to 6 months postoperatively. Follow-up electrocardiography and color Doppler echocardiography were performed postoperatively. RESULTS: The mean aortic crossclamping time was 84.0 +/- 25.5 minutes, and cardiopulmonary bypass time was 139.4 +/- 39.1 minutes. There was no abnormal bleeding due to bipolar radiofrequency ablation. Three patients (1.57%) died of low cardiac output syndrome in hospital at 2, 3, and 5 days after surgery. Major perioperative complications include reoperation for bleeding (n = 1), reoperation for wound infection (n = 1), intra-aortic balloon pump placement (n = 2), and renal failure (n = 2). All other patients were discharged without complications. The mean follow-up time was 17.4 +/- 11.8 months with a follow-up rate of 95.3%. There were no cases of late death, complete atrioventricular block, or anticoagulation-induced complications. Of 158 patients who were followed up for 1 year, sinus rhythm was maintained in 125 (79.11%). CONCLUSIONS: Concomitant bipolar radiofrequency ablation is an effective and safe technique for treating atrial fibrillation in patients with rheumatic heart disease undergoing valve replacement, with promising follow-up results. PMID- 22676980 TI - Management of an aortoesophageal fistula caused by Kirschner wire migration in a patient with arteria lusoria. PMID- 22676981 TI - Circumferential intimal tear in type A aortic dissection with intimo-intimal intussusception into left ventricle and left main coronary artery occlusion. PMID- 22676982 TI - Inadvertent injection of formalin mistaken for local anesthetic agent: report of a case. AB - Chemical facial cellulitis, while commonly seen in domestic accidents or attempted suicide, is uncommon in the dental office and hence rarely addressed in the dental literature. We present an unusual case of chemical facial cellulitis caused by inadvertent injection of formalin into the soft tissues of the oral cavity, which was mistaken for local anesthesia solution. This report comprises the immediate symptoms, possible root cause, and management of the difficult situation. We also provide some guidelines to avoid such unfortunate events. PMID- 22676983 TI - A comparative study of the effectiveness of sinus bone grafting with recombinant human bone morphogenetic protein 2-coated tricalcium phosphate and platelet-rich fibrin-mixed tricalcium phosphate in rabbits. AB - OBJECTIVES: The objective of this histologic study was to evaluate platelet-rich fibrin (PRF)-mixed tricalcium phosphate (TCP) and recombinant human bone morphogenic protein 2 (rhBMP-2)-coated TCP in their potential to enhance bone regeneration in sinus elevation in rabbits as well as in their inflammatory features. STUDY DESIGN: Bilateral round-shaped defects (diameter 8.0 mm) were formed in the maxillary anterior sinus walls of 36 New Zealand white rabbits. The defects were grafted with TCP only (control group), with rhBMP-2-coated TCP (experimental group A) and with PRF-mixed TCP (experimental group B). Each group included 12 rabbits. The animals were killed at 3 days, 1 week, 2 weeks, 4 weeks, 6 weeks, and 8 weeks. The specimens underwent decalcification and were stained for histologic analysis. RESULTS: There were no significant differences in inflammatory features among the groups at 3 days or the first week after operation. In a histomorphometric analysis, the new bone formation ratio showed significant differentiation between groups A and B. The TCP-only control group showed a relatively lower bone formation ratio rather than the experimental groups. The PRF-mixed TCP group showed a larger bone formation area, compared with both the control group and group A. CONCLUSIONS: In the results of the histologic evaluation (hematoxylin-eosin, Masson trichrome stain), the experimental groups A and B showed rapid bone formation, remodeling, and calcification in the second week. Moreover, there was a significant difference between those experimental groups and the control group in the new bone formation area at the fourth, sixth, and eighth weeks. The PRF-mixed TCP showed more rapid bone healing than the rhBMP-2-coated TCP or the TCP-only control. PMID- 22676984 TI - Modified face-lift approach combined with a superficially anterior and superior based sternocleidomastoid muscle flap in total parotidectomy. AB - OBJECTIVES: The authors evaluate a modified total parotidectomy performed through a modified face-lift incision integrated with a superficially anterior and superior pedicled sternocleidomastoid muscle (SASSCM) flap. STUDY DESIGN: Records of 86 cases of total parotidectomy were reviewed retrospectively. Clinical evaluation of cosmetic gratification, presence or absence of gustatory flushing or sweating, functional reversion of the seventh cranial nerve and great auricular nerve (GAN) were undertaken by 3 investigators independent to the operators. RESULTS: This group presents a mean follow-up of twenty-six months. The average scale of cosmetic gratification from patients and investigators are 7.97 and 7.56, respectively. Almost total complaints about anesthesia in upper cervical part and cheek disappeared within three months postoperatively. Neither in objective test nor from subjective complaint was gustatory sweating identified in present study. CONCLUSIONS: The authors' technique is esthetically pleasing and efficacious to prevention of gustatory sweating in total parotidectomy. PMID- 22676985 TI - Histomorphometric examination of long-term changes in temporomandibular joints after mandibular lengthening by distraction osteogenesis in rabbits. AB - OBJECTIVE: The purpose of this study was to evaluate long-term histomorphometric changes in temporomandibular joints (TMJs) of rabbits after mandibular distraction osteogenesis (DO). STUDY DESIGN: Twenty-six rabbits were used in this study. Two of them served as control subjects, and the remaining 24 underwent DO procedures in their left mandibular bodies. After a latency period of 5 days, 5 mm lengthening was performed at a rate of 1 mm/d. The rabbits in the experimental group were randomly divided into 4 subgroups and killed after 1, 2, 4, and 6 months. TMJs from both sides were harvested and prepared with hematoxylin and eosin stain for histomorphometric examination under an optical microscope. RESULTS: Compared with control subjects and nondistracted sides, fibrous articular, proliferative, and hypertrophic areas were significantly increased (P < .05) in the first 2 months in distracted sides. The changes were insignificant in the fourth and sixth postoperative months. CONCLUSION: Unilateral mandibular distraction of 5 mm was found to be well tolerated and no degenerative changes were observed histologically in the rabbit TMJs in the long-term period. PMID- 22676987 TI - Intraorally exposed anterior Stafne bone defect: a case report. AB - Anterior Stafne bone defect is a rare lingual bone depression mostly seen in the mandibular canine-premolar region; however, exposure of the defect into the oral cavity is quite rare. In this article, a case of anterior Stafne bone cavity, which can be seen in the intraoral examination, is presented with clinical features. Surgery is not considered for this case and after 2 years of follow-up, the defect remained stable. PMID- 22676986 TI - Mandible reconstruction assisted by preoperative virtual surgical simulation. AB - OBJECTIVE: In this study, we evaluated the clinical efficacy of mandible reconstruction with preoperative virtual planning, which focused on esthetics and occlusion. STUDY DESIGN: A series of 9 patients were enrolled prospectively to undergo mandibulectomy and simultaneous reconstruction. Preoperative spiral CT scans of the maxillofacial region and the fibula region were performed. Virtual surgery of tumor resection and fibula reconstruction was performed in the Mimics platform. The reconstructed mandible models were fabricated with CAD/CAM technique. The reconstruction plate and the positioning template were accommodated to the stereolithographic model as the surgical template. RESULTS: Surgery was performed accurately according to the templates. All the fibula flaps survived. The appearance and occlusion of the patients were satisfactory. CONCLUSIONS: With preoperative virtual planning, the spatial relationship of the mandible and the fibula graft can be planned individually, which helps achieve optimum appearance and occlusion relationship. PMID- 22676988 TI - Osteoplastic ameloblastoma: a case report and literature review. AB - Ameloblastoma with bone formation is rare. We report a case of a 55-year-old woman with ameloblastoma accompanied by prominent osteoplasia. Histopathological examination exhibited an abundant stromal component between tumor nests. Therefore, she was diagnosed as the desmoplastic variant, except for the numerous bone trabeculae. The distinction between new bone formation and invasion of the bone marrow poses a problem. A thin rim of fibrous bone that can be accentuated by Masson-trichrome staining suggests the former. PMID- 22676989 TI - Bilateral maxillary duplication: case report and literature review. AB - Accessory maxillary jaws are extremely rare occurrences. Currently, there is only 1 report of bilateral accessory maxillary jaws in the English-language literature. We present a case of a 7-year-old girl with bilateral bony exostoses extending from the maxillary tuberosities. The patient also had restricted protrusive and lateral excursive movements of the mandible. The histologic report revealed teeth in various developmental stages within the bony exostoses. We concluded that these structures were an isolated form of bilateral accessory maxillary jaws. PMID- 22676990 TI - Clinical outcomes after the use of complete autologous oral mucosa equivalents: preliminary cases. AB - OBJECTIVE: Previously, we reported how to obtain complete autologous oral mucosa equivalents (CAOMEs) composed of an autologous plasma scaffold and fibroblasts together with immature keratinocytes able to build an oral epithelium with a structure similar to that of the oral mucosa. In this study, we present the clinical outcomes after applying our CAOMEs as grafts. STUDY DESIGN: Four patients who needed a CAOME to restore a defect of oral mucosa were selected. Two of the patients suffered from ankyloglossia, and the other 2 required a restoration of the keratinized gum of the alveolar rim. To assess the outcomes, the scale designed by Ewers et al. was used. RESULTS: Clinical and functional improvements were achieved in the patients with ankyloglossia. In cases of gum restoration, the mucosa was regenerated and a prosthetic restoration with implants was achieved. CONCLUSIONS: The results obtained points to the potential use of CAOME in intraoral lining. PMID- 22676991 TI - [Use of a direct immunofluorescence assay in the rapid and specific diagnosis of adenoviral conjunctivitis]. PMID- 22676992 TI - Long-term impact of intrauterine fetal death on quality of life and depression: a case-control study. AB - BACKGROUND: Intrauterine fetal death (IUFD) is a serious incidence that has been shown to impact mothers' psychological well-being in the short-term. Long-term quality of life (QOL) and depression after IUFD is not known. This study aimed to determine the association between intrauterine fetal death and long-term QOL, well-being, and depression. METHODS: Analyses were performed on collected data among 106 women with a history of intrauterine fetal death (IUFD) and 262 women with live births, 5-18 years after the event. Univariable and multivariable linear and logistic regression models were used to quantify the association between previous fetal death and long-term QOL, well-being and depression. QOL was assessed using the QOL Index (QLI), symptoms of depression using the Center for Epidemiological Studies Depression Scale (CES-D), and subjective well-being using the General Health Questionnaire 20 (GHQ-20). RESULTS: More of the cases had characteristics associated with lower socioeconomic status and did not rate their health as good as did the controls. The QLI health and functioning subscale score was slightly but significantly lower in the cases than in the controls (22.3. vs 23.5, P = .023). The CES-D depressed affect subscale score (2.0 vs 1.0, P = 0.004) and the CES-D global score (7.4 vs 5.0, P = .017) were higher in the cases. Subjective well-being did not differ between groups (20.6 vs 19.4, P = .094). After adjusting for demographic and health-related variables, IUFD was not associated with global QOL (P = .674), subjective well-being (P = .700), or global depression score (adjusted odds ratio = 0.77, 95% confidence interval 0.37 1.57). CONCLUSIONS: Women with previous IUFD, of which the majority have received short-term interventions, share the same level of long-term QOL, well-being and global depression as women with live births only, when adjusted for possible confounders. TRIAL REGISTRATION: The study was registered at http://www.clinicaltrials.gov, with registration number NCT 00856076. PMID- 22676993 TI - Structural analysis of Herbaspirillum seropedicae lipid-A and of two mutants defective to colonize maize roots. AB - Lipid-A was isolated by mild acid hydrolysis from lipopolysaccharides extracted from cells of Herbaspirillum seropedicae, strain SMR1, and from two mutants deficient in the biosynthesis of rhamnose (rmlB- and rmlC-). Structural analyzes were carried out using MALDI-TOF and derivatization by per-O-trimethylsilylation followed by GC-MS in order to determine monosaccharide and fatty acid composition. De-O-acylation was also performed to determine the presence of N linked fatty acids. Lipid-A from H. seropedicae SMR1 showed a major structure comprising 2-amino-2-deoxy-glucopyranose-(1->6)-2-amino-2-deoxy-glucopyranose phosphorylated at C4' and C1 positions, each carrying a unit of 4-amino-4-deoxy arabinose. C2 and C2' positions were substituted by amide-linked 3-hydroxy dodecanoic acids. Both rhamnose-defective mutants showed similar structure for their lipid-A moieties, except for the lack of 4-amino-4-deoxy-arabinose units attached to phosphoryl groups. PMID- 22676994 TI - Dissolution and regeneration of collagen fibers using ionic liquid. AB - Native skin collagen fibers were successfully dissolved in the ionic liquid, 1 butyl-3-methylimidazolium chloride ([BMIM]Cl), and regenerated in different precipitators. The observation by polarized optical microscopy showed that the crystal structure of collagen fibers had been destroyed by [BMIM]Cl during the heating. Temperature-dependent FTIR was applied to detect the structural change of collagen/[BMIM]Cl during dissolving. The structure of regenerated collagen was characterized by FTIR and XRD. It showed that the triple helical structure of collagen had been partly destroyed during the dissolution and regeneration. The film forming ability and the thermostability of the regenerated collagen was highly dependent on the precipitating treatment. The possible mechanisms of dissolving of collagen in [BMIM]Cl and the regeneration in the precipitators have been proposed. The collagen/cellulose composite with different forms (film, fiber, gel) can be successfully prepared by using [BMIM]Cl as medium. PMID- 22676995 TI - Preparation and characterization of chitin hydrogels by water vapor induced gelation route. AB - A novel method of chitin hydrogel preparation, called vapor induced gelation, using exposure of chitin/N-methyl-pyrrolidone/LiCl solution to water vapors is presented. Compared to gelation induced by direct immersion in water, hydrogels are characterized by smaller deformation during gelation (area shrinkage is 20% instead of 65%), larger water volume fraction (75 instead of 62%, v/v) and 10 times higher apparent compression moduli. Their nanostructure consists of thicker and larger crystalline platelets network (thickness=37 A, apparent coherent crystalline size L020=145 A) comparatively to direct immersion gels (25 A and L020=95 A). Drug delivery potential of chitin hydrogels was determined for non interactive low molecular molecules. PMID- 22676996 TI - Laccase-based dye decolorization using agro-wastes: comment on Santhanam et al. PMID- 22676997 TI - Prediction of the brain temperature from other body temperatures in hypothermia induced rats by using artificial neural networks. AB - In this study, a microcontroller based temperature controlled hypothermia induction system is realized. The novelty of the experimental system is in using a thermoelectric Peltier cooler to bring the body temperature to hypothermic levels. The right and left ear, rectum, and brain temperatures of a rat are measured with this system. Then, an artificial neural network (ANN) is trained using temperature data to predict brain temperature from other body temperatures. It is shown that the system has the capability to predict the brain temperature with low error from rectum temperature measurements. The results from this empirical prototype also show that it is possible to use the system on humans to induce local hypothermia safely, where an interior temperature probe in the scalp is eliminated. PMID- 22676998 TI - Simple statistical inference algorithms for task-dependent wellness assessment. AB - Stress is a key indicator of wellness in human beings and a prime contributor to performance degradation and errors during various human tasks. The overriding purpose of this paper is to propose two algorithms (probabilistic and non probabilistic) that iteratively track stress states to compute a wellness index in terms of the stress levels. This paper adopts the physiological view-point that high stress is accompanied with large deviations in biometrics such as body temperature, heart rate, etc., and the proposed algorithms iteratively track these fluctuations to compute a personalized wellness index that is correlated to the engagement levels of the tasks performed by the user. In essence, this paper presents a quantitative relationship between temperature, occupational stress, and wellness during different tasks. The simplicity of the statistical inference algorithms make them favorable candidates for implementation on mobile platforms such as smart phones in the future, thereby providing users an inexpensive application for self-wellness monitoring for a healthier lifestyle. PMID- 22676999 TI - Porcine uterus cryopreservation: an analysis of contractile function using different uterotonics. AB - Cryopreservation of whole organs has become increasingly successful in recent years, and establishing reliable methods for confirming the success of specific cryopreservation procedures has therefore become extremely important. On the assumption that methods such as histological evaluation do not provide definitive evidence of long-term cryopreservation and that clear signs of conserved function in an organ are good evidence of its viability, contractile function was analysed in porcine uteri (n=60), either after long-term (group A) or short-term (group B) cryopreservation and post-thaw treatment with three different uterotonics. A slow freezing protocol was used to preserve the organs. Fifteen fresh uteri were analysed similarly for contractile function, which was evaluated by measuring intrauterine pressure after administration of oxytocin, prostaglandin E(1) (PGE(1)), and carbachol. After cryopreservation, all but three uteri (95%) showed rhythmic contractions similar to those in fresh uteri except for differences in the heights of contraction peaks, with lower contractions in PGE(1) subgroup B (P<0.05). With the exception of three nonresponsive uteri in group A, there were no differences in contractility between uteri after long-term cryopreservation and fresh uteri. The results of this study thus contribute to the debate on whether slow freezing or vitrification techniques are best for whole-organ cryopreservation. In summary, (1) preservation of muscular function in porcine uteri is feasible with a slow freezing protocol; (2) measurement of contractile function following administration of uterotonics is a useful method of confirming functionality; and (3) long-term cryopreservation does not significantly impair post-thaw contractibility in comparison with fresh uteri. PMID- 22677000 TI - Aromatase inhibitors and mood disturbances. AB - We describe the case of a 56-year old woman with no prior psychiatric history who was diagnosed with hormone receptor positive early-stage breast cancer and who developed severe mood changes after administration of anastrozole, which resolved after discontinuation of treatment. Aromatase inhibitors (AIs) are the preferred hormonal approach for postmenopausal women with estrogen hormone sensitive breast cancer. The third-generation agents (anastrozole, letrozole, and exemestane) have been shown to be more effective and safer than the selective estrogen receptor modulators tamoxifen and raloxifen. Treatment strategies with these agents include the use of an AI as an upfront strategy for 5 years, as a sequential approach after 2-3 years of tamoxifen, or as extended use after the classical 5 years of tamoxifen. The side effects of AIs, as compared with selective estrogen receptor modulators, are different, reflecting the specific mechanism of action of these drugs. AIs are well tolerated and cause a lower incidence of gynecological symptoms (vaginal bleeding, discharge, and endometrial neoplasia), venous thromboembolic events, and hot flashes compared with tamoxifen. However, the use of AIs have been associated with loss of bone density, arthralgia, myalgia, a negative effect on lipid metabolism, and cardiovascular risk (Tomao et al., 2011). Mood disturbances, somnolence, anxiety, fatigue, hot flashes, and memory impairment have been reported among patients receiving anastrozole as adjuvant therapy. PMID- 22677003 TI - Risk of intestinal lymphoma in undiagnosed coeliac disease: results from a registered population with different coeliac disease prevalence. AB - BACKGROUND: Coeliac disease is often undiagnosed, early diagnosis and treatment could be relevant to avoid fearful complications as intestinal lymphoma. Our aim is to estimate the risk of intestinal lymphoma in undiagnosed coeliac patients, evaluating the real incidences and applying different theoretical settings of coeliac prevalence. METHODS: We collected cases of intestinal lymphomas from the Lombardy Cancer Registry and coeliac patients through computerized search of all Pathology Departments; duodenal pathological reports compatible with a Marsh 3 grade were included. The lymphoproliferative risk was calculated for theoretical different settings of coeliac prevalence (from 1:50 to 1:200), relative risks for intestinal lymphomas and compared to the real incidence of the lymphomas in this population. RESULTS: Population consisted in 815,362 inhabitants; during the investigated period of time, 237 intestinal lymphomas and 326 coeliac patients were diagnosed. None of the coeliac patients had lymphoma. In the different scenarios calculated and compared with the real lymphoma incidence the relative risks of undiagnosed celiac disease for gastrointestinal B- and T-cell lymphomas ranges from 1.0 to 2.0 for 1:100 coeliac disease prevalence. CONCLUSIONS: Undiagnosed coeliac patients have no increased risk of developing intestinal lymphoma; population screening programmes, aimed at early diagnosis of lymphoma may not be useful in this setting. PMID- 22677004 TI - Comment to "high tissue-transglutaminase antibody level predicts small intestinal villous atrophy in adult patients at high risk of coeliac disease". PMID- 22677001 TI - Intestinal peptidases form functional complexes with the neutral amino acid transporter B(0)AT1. AB - The brush-border membrane of the small intestine and kidney proximal tubule are the major sites for the absorption and re-absorption of nutrients in the body respectively. Transport of amino acids is mediated through the action of numerous secondary active transporters. In the mouse, neutral amino acids are transported by B(0)AT1 [broad neutral ((0)) amino acid transporter 1; SLC6A19 (solute carrier family 6 member 19)] in the intestine and by B(0)AT1 and B(0)AT3 (SLC6A18) in the kidney. Immunoprecipitation and Blue native electrophoresis of intestinal brush border membrane proteins revealed that B(0)AT1 forms complexes with two peptidases, APN (aminopeptidase N/CD13) and ACE2 (angiotensin-converting enzyme 2). Physiological characterization of B(0)AT1 expressed together with these peptidases in Xenopus laevis oocytes revealed that APN increased the substrate affinity of the transporter up to 2.5-fold and also increased its surface expression (V(max)). Peptide competition experiments, in silico modelling and site-directed mutagenesis of APN suggest that the catalytic site of the peptidase is involved in the observed changes of B(0)AT1 apparent substrate affinity, possibly by increasing the local substrate concentration. These results provide evidence for the existence of B(0)AT1-containing digestive complexes in the brush border membrane, interacting differentially with various peptidases, and responding to the dynamic needs of nutrient absorption in the intestine and kidney. PMID- 22677005 TI - Pill impaction mimicking appendicitis in ulcerative colitis. PMID- 22677007 TI - The effects of doxycycline and micronized purified flavonoid fraction on human vein wall remodeling are not hypoxia-inducible factor pathway-dependent. AB - BACKGROUND: Doxycycline and micronized purified flavonoid fraction (MPFF) modulate vein wall remodeling that may be associated with hypoxia in varicose veins (VVs), vein graft stenosis, and deep venous thrombosis. We recently reported that in vitro exposure of non-VV (NVVs) and VVs to hypoxic conditions activates the hypoxia-inducible factor (HIF) pathway. This study investigated the in vitro effects of doxycycline and MPFF on the HIF pathway in hypoxic NVVs and VVs. METHODS: Six NVVs and six VVs obtained from surgery were used to prepare vein organ cultures, which were exposed to hypoxia (1% O(2)), with and without MPFF (10(-5) mol/L) or doxycycline (5 MUg/mL) for 16 hours. The veins were analyzed for HIF-1alpha, HIF-2alpha, and their target gene expression, with real time polymerase chain reaction and Western blot. The differences between gene expressions were tested with one-way analysis of variance with repeated measures, followed by the Dunnett test for multiple comparisons. P < .05 was considered significant. RESULTS: Treatment of NVV organ cultures exposed to hypoxia with doxycycline or MPFF did not significantly alter the expression of HIF-1alpha and HIF-2alpha messenger (m)RNA and protein compared with untreated. Doxycycline also did not significantly affect the expression of HIF-1alpha and HIF-2alpha mRNA and protein in VVs exposed to hypoxia compared with untreated VVs. However, MPFF significantly reduced the expression of HIF-1alpha but not HIF-2alpha mRNA in VVs exposed to hypoxia compared with untreated VVs. Interestingly, the reduction of the expression of HIF-1alpha mRNA in VVs by MPFF was not reflected at the protein level. The mRNA expression of HIF target genes, namely glucose transporter-1, carbonic anhydrase-9, vascular endothelial growth factor, B-cell lymphoma 2/adenovirus E1B 19-kDa protein-interacting protein 3, prolyl hydroxylase domain 2, and prolyl hydroxylase domain-3, was not significantly altered in NVVs and VVs exposed to hypoxia and treated with doxycycline or MPFF compared with those untreated. CONCLUSIONS: Doxycycline and MPFF at a concentration corresponding to a therapeutic dose do not alter the activation of the HIF pathway in NVV and VV organ cultures exposed to hypoxia. Our findings suggest vein wall remodeling actions in NVVs and VVs are likely not HIF-dependent. PMID- 22677006 TI - Real-time reverse transcriptase PCR assay for improved detection of human metapneumovirus. AB - BACKGROUND: Human metapneumovirus (HMPV) is a paramyxovirus with multiple genetic lineages that is a leading cause of acute respiratory disease. Several RT-PCR assays have been described based on limited available sequence data. OBJECTIVES: To develop a broadly reactive real-time RT-PCR assay for HMPV that allows for a rapid, sensitive, and specific detection in a clinical or research setting. STUDY DESIGN: Three published assays for HMPV were modified based on analysis of multiple HMPV sequences obtained from GenBank. Original and modified assays were tested against prototype HMPV strains from each genetic sublineage, multiple isolates of HMPV from different years, a collection of clinical specimens, and commercial validation panels. RESULTS: A number of potential sequence mismatches with diverse HMPV strains were identified. Modifications were made to oligonucleotides to improve annealing efficiency. Primers and probes based on newer sequence data offered enhanced detection of all subgroups, especially for low titer specimens. The new primers and probe detected multiple clinical isolates of HMPV collected over a twenty-year period. The modified assay improved detection of HMPV in a panel of clinical specimens, and correctly identified HMPV samples in two commercial validation sets. CONCLUSIONS: We report a modified real time RT-PCR assay for HMPV that detects all genetic lineages with high sensitivity. PMID- 22677008 TI - Survival benefits of revascularization in patients with critical limb ischemia and renal insufficiency. AB - BACKGROUND: Evidence for the best treatment strategy for patients with critical limb ischemia (CLI) at different stages of renal insufficiency (RI) is rare. Therefore, we determined the benefit of revascularization vs medical therapy (MT) only in CLI patients with different levels of RI. METHODS: This intention-to treat cohort study with follow-up at 2, 6, and 12 months was conducted in a consecutive series of 351 patients with CLI. Revascularization by surgical (78 patients) or endovascular techniques (191 patients) was performed in 269 patients. MT as first-line therapy was administered in 82 patients. Patients were grouped according to glomerular filtration rate (GFR), estimated with the Modification of Diet in Renal Disease equation, into absent/mild RI (estimated GFR [eGFR], >= 60 mL/min/1.73 m(2)), moderate RI (eGFR, 30-59 mL/min/1.73 m(2)), and severe RI (eGFR, <30 mL/min/1.73 m(2) or dialysis). Primary outcome measures were overall and amputation-free survival. Cox regression models adjusted for baseline characteristics after Kaplan-Meier survival estimates were performed. RESULTS: The mean age differed significantly between groups (P < .001), and patients with absent/mild RI were more often men (P < .001) or smokers (P < .001) and less often hypertensive (P < .001). Risk factor adjustment showed that revascularized CLI patients with absent/mild RI had a longer amputation-free survival (hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.26-0.82; P = .008), higher limb salvage (HR, 0.29; 95% CI, 0.17-0.91; P < .029), and better clinical success than MT patients (HR, 0.33; 95% CI, 0.17-0.65; P = .001). The moderate RI group benefited from revascularization in overall survival (HR, 0.51; 95% CI, 0.26-0.99; P = .049), amputation-free survival (HR, 0.51; 95% CI, 0.29 0.90; P = .020), and clinical success (HR, 0.42; 95% CI, 0.22-0.80; P = .008). A beneficial effect on overall survival was found even in patients with severe RI when revascularized (HR, 0.33; 95% CI, 0.12-0.91; P = .032 vs MT). CONCLUSIONS: Patients with CLI may benefit from revascularization compared with MT alone at all levels of renal impairment. Thus, revascularization should not be withheld in CLI patients at any level of RI. PMID- 22677009 TI - A comparison of tibial artery bypass performed with heparin-bonded expanded polytetrafluoroethylene and great saphenous vein to treat critical limb ischemia. AB - BACKGROUND: Expanded polytetrafluoroethylene (ePTFE) bonded with heparin (HePTFE) has been reported to perform equivalent to saphenous vein graft (SVG) for below knee bypass. This series examines outcomes for tibial artery bypass using HePTFE and SVG over a contemporaneous time period. METHODS: A retrospective analysis of prospectively collected data was conducted for 112 tibial bypasses (62 HePTFE, 50 SVG) performed from November 2006 to January 2009. Demographics for age, sex, race, diabetes mellitus, and end-stage renal disease were similar. Indications for revascularization were also similar: disabling claudication, 9%; rest pain, 25%; and tissue loss, 66%. The HePTFE group included more reoperative procedures (45% vs 26%). All HePTFE bypasses were performed using an autologous vein patch at the distal anastomosis. Postoperative graft surveillance by pulse examination, ankle-brachial index, and duplex ultrasound imaging occurred at 1, 3, 6, and 12 months. Follow-up ranged from 1 to 12 months. Kaplan-Meier and Cox regression analysis evaluated results in patients with no missing variables. RESULTS: HePTFE and SVG bypasses demonstrated no significant differences in target tibial artery distribution: anterior tibial (15 vs 17), dorsalis pedis (4 vs 5), posterior tibial (22 vs 16), and peroneal (21 vs 12). Graft occlusion occurred in 19 patients (16.9%) during follow-up. Primary patency at 1 year was 75.4% for HePTFE and 86.0% for SVG. There was no significant difference in primary patency due to sex (male, 78%; female, 84%), race (white, 82%; African American, 77%), or diabetes mellitus (no diabetes mellitus, 84%; diabetes mellitus, 76%). End-stage renal disease resulted in decreased patency (57%), with an eightfold reduction (95% confidence interval, 1.8%-39.8%; P = .006). SVG patients had a lower risk of occlusion/death (95% confidence interval, 14.2%-94.5%; P > .05). Sixteen amputations were performed, with no significant difference based on conduit. CONCLUSIONS: This experience indicates a trend for single-segment quality saphenous vein to remain the conduit of choice for tibial artery bypass compared with HePTFE. Factors relevant to decreased 1-year patency for the entire cohort were end-stage renal disease and nonhealing ulceration as the indication for revascularization. Although relatively short-term, these results do support HePTFE as a viable alternative conduit for patients with absent or poor quality saphenous vein who need a tibial bypass. PMID- 22677010 TI - Tracking contaminants in seabirds of Arctic Canada: temporal and spatial insights. AB - Levels and trends of persistent organic pollutants and trace elements in seabirds breeding in the vast Canadian Arctic have been monitored since 1975. Data from this monitoring have indicated both spatial and temporal variation across the region, attributable in part to differences in species' diets, differences in regional deposition patterns, and unidirectional trends in contaminants reaching this area from emissions in temperate and tropical areas to the south. Seabird tissues have served as effective biomonitors to examine this variation, and national and international collaboration in this monitoring effort has promoted valuable synthetic assessments of spatial and temporal patterns in Arctic contaminants. Here we review the history of the monitoring program, the critical role played by Environment Canada's National Wildlife Specimen Bank, and we summarize important spatial and temporal trends in various contaminants in Canadian Arctic seabirds. PMID- 22677011 TI - Comprehensive assessment of heavy metal contamination in sediment of the Pearl River Estuary and adjacent shelf. AB - Total metal concentrations (Cr, Ni, Cu, Zn, and Pb), acid volatile sulfide and simultaneously extracted metals (AVS-SEM), and heavy metal fractionation were used to assess the heavy metals contamination status and ecological risk in the sediments of the Pearl River Estuary (PRE) and adjacent shelf. Elevated concentrations at estuarine sites and lower concentrations at adjacent shelf sites are observed, especially for Cu and Zn. Within the PRE, the concentration of heavy metals in the western shore was mostly higher than that in the middle shore. The metals from anthropogenic sources mainly occur in the labile fraction and may be taken up by organisms as the environmental parameters change. A combination of total metal concentrations, metal contamination index and sequential extraction analysis is necessary to get the comprehensive information on the baseline, anthropogenic discharge and bioavailability of heavy metals. PMID- 22677012 TI - Self-assembly of supra-amphiphiles based on dual charge-transfer interactions: from nanosheets to nanofibers. AB - With the elaborate engineering of supra-amphiphiles based on dual charge-transfer interactions, the rational design and programmable transformation of well-defined 1D and 2D nanostructures have been demonstrated. First, H-shaped supra amphiphiles are successfully obtained on the basis of the directional charge transfer interactions of naphthalene diimide and naphthalene, which self-assemble in water to form 2D nanosheets. Second, by complexation of the H-shaped supra amphiphiles with pyrene derivatives, the 2D nanosheets transform into ultralong 1D nanofibers. Therefore, this line of research represents a successful example of supramolecular engineering and has enriched its realm. PMID- 22677013 TI - Leaching of indium from obsolete liquid crystal displays: comparing grinding with electrical disintegration in context of LCA. AB - In order to develop an effective recycling system for obsolete Liquid Crystal Displays (LCDs), which would enable both the leaching of indium (In) and the recovery of a pure glass fraction for recycling, an effective liberation or size reduction method would be an important pre-treatment step. Therefore, in this study, two different types of liberation methods: (1) conventional grinding, and (2) electrical disintegration have been tested and evaluated in the context of Life Cycle Assessment (LCA). In other words, the above-mentioned methods were compared in order to find out the one that ensures the highest leaching capacity for indium, as well as the lowest environmental burden. One of the main findings of this study was that the electrical disintegration was the most effective liberation method, since it fully liberated the indium containing-layer, ensuring a leaching capacity of 968.5mg-In/kg-LCD. In turn, the estimate for the environmental burden was approximately five times smaller when compared with the conventional grinding. PMID- 22677014 TI - Prioritizing material recovery for end-of-life printed circuit boards. AB - The increasing growth in generation of electronic waste (e-waste) motivates a variety of waste reduction research. Printed circuit boards (PCBs) are an important sub-set of the overall e-waste stream due to the high value of the materials contained within them and potential toxicity. This work explores several environmental and economic metrics for prioritizing the recovery of materials from end-of-life PCBs. A weighted sum model is used to investigate the trade-offs among economic value, energy saving potentials, and eco-toxicity. Results show that given equal weights for these three sustainability criteria gold has the highest recovery priority, followed by copper, palladium, aluminum, tin, lead, platinum, nickel, zinc, and silver. However, recovery priority will change significantly due to variation in the composition of PCBs, choice of ranking metrics, and weighting factors when scoring multiple metrics. These results can be used by waste management decision-makers to quantify the value and environmental savings potential for recycling technology development and infrastructure. They can also be extended by policy-makers to inform possible penalties for land-filling PCBs or exporting to the informal recycling sector. The importance of weighting factors when examining recovery trade-offs, particularly for policies regarding PCB collection and recycling are explored further. PMID- 22677015 TI - Thermal treatment for recovery of manganese and zinc from zinc-carbon and alkaline spent batteries. AB - The aim of this paper is the recovery of manganese and zinc from a mixture of zinc-carbon and alkaline spent batteries, containing 40.9% of Mn and 30.1% of Zn, after preliminary physical treatment followed by removal of mercury. Separation of the metals has been carried out on the basis of their different boiling points, being 357 degrees C and 906 degrees C the boiling point of mercury and zinc and 1564 degrees C the melting point of Mn(2)O(3). Characterization by chemical analysis, TGA/DTA and X-ray powder diffraction of the mixture has been carried out after comminution sieving and shaking table treatment to remove the anodic collectors and most of chlorides contained in the mixture. The mixture has been roasted at various temperatures and resident times in a flow of air to set the best conditions to remove mercury that were 400 degrees C and 10 min. After that, the flow of air has been turned into a nitrogen one (inert atmosphere) and the temperatures raised, thus permitting the zinc oxide to be reduced to metallic zinc by the carbon present in the original mixture and recovered after volatilization as a high grade concentrate, while manganese was left in the residue. The recovery and the grade of the two metals, at 1000 degrees C and 30 min residence time, were 84% and 100% for zinc and 85% and 63% for manganese, respectively. The recovery of zinc increased to 99% with a grade of 97% at 1200 degrees C and 30 min residence time, while the recovery and grade of manganese were 86% and 87%, respectively, at that temperature. Moreover, the chlorinated compounds that could form by the combustion of the plastics contained in the spent batteries, are destroyed at the temperature required by the process. PMID- 22677016 TI - Technical, economic and environmental analysis of a MSW kerbside separate collection system applied to small communities. AB - The main aim of this study was to evaluate the costs and environmental impacts induced by a fixed model of MSW kerbside separate collection system for communities up to 10,000 inhabitants, in order to evaluate the convenience for the smaller municipalities to unite and form more economically and environmentally sound systems. This topic is important not only due to the large number of small municipalities (e.g. in Italy 72% of the municipalities has less than 5000 inhabitants) but also to the fact that separate collection systems are typically designed to take into account only the technical and economic aspects, which is a practice but not acceptable in the light of the sustainable development paradigm. In economic terms, between 1000 and 4000 inhabitants, the annual per capita cost for vehicles and personnel decreased, with a maximum at approximately 180?/inhabitants/year; while, from 5000 up to 10,000 inhabitants, the annual per capita cost was practically constant and equal to about 80?/inhabitants/year. For the municipalities of less than 5000 inhabitants, from an economic point of view the aggregation is always advantageous. The environmental impacts were calculated by means of the Life Cycle Assessment tool SimaPro 7.1, while the economic-environmental convenience was evaluated by combining in a simple multicriteria analysis, the annual total per capita cost (?/inhabitants/year) and the annual total per capita environmental impact (kEco indicator point/inhabitants/year), giving the same importance to each criteria. The analysis was performed by means of the Paired Comparison Technique using the Simple Additive Weighting method. The economic and environmental convenience of the aggregation diminishes with the size of the municipalities: for less than 4000 inhabitants, the aggregation was almost always advantageous (91.7%); while, for more than or equal to 5000 inhabitants, the aggregation was convenient only in 33.3% of the cases. On the whole, out of 45 cases examined, for the municipalities from 1000 to 9000 inhabitants, the aggregation was both economically and environmentally convenient in 60.0% of the cases. PMID- 22677018 TI - Dental stem cells for craniofacial tissue engineering. AB - This article focuses on the biological characterization and discussion of the potential application of oral-derived adult stem cells for craniofacial tissue engineering applications. The authors reviewed experimental (in vitro and in vivo) and clinical reports regarding the isolation, characterization, modulation, and translational clinical application of human precursor cell populations derived from postnatal dental tissues. Five different human dental stem/progenitor cell populations have been isolated and characterized. These postnatal populations present mesenchymal stem cell-like characteristics and enjoy forceful capabilities regarding the differentiation into odontogenic/osteogenic lineages, supporting evidence--in preclinical and clinical trials--for the regeneration of oral/dental tissues. PMID- 22677017 TI - Peroxisome proliferator-activated receptor activation increases imatinib uptake and killing of chronic myeloid leukemia cells. AB - Low pretreatment expression of the imatinib uptake transporter human organic cation transporter 1 (hOCT1) is associated with inferior complete cytogenetic response rates, progression-free survival, and overall survival in imatinib treated chronic myeloid leukemia (CML). Upregulation of hOCT1 can therefore increase the uptake of imatinib. The hOCT1 gene is transactivated by hepatocyte nuclear factor 4alpha in human liver, and peroxisome proliferator-activated receptors (PPAR) alpha and gamma activation increases OCT1 expression in mouse hepatocytes. Here we report that no isoform of hepatocyte nuclear factor 4alpha is expressed in CML lines or in CML primary cells. In contrast, both PPARalpha and gamma were expressed in all CML cell lines and primary cells studied. PPARalpha agonist treatment increased imatinib killing of CML KCL22 cells and primitive CD34(+) cells, and also upregulates hOCT1 gene expression and increases imatinib uptake into KCL22 cells and primary cells. PPARalpha agonists might potentially be of clinical use in CML patients failing imatinib. PMID- 22677019 TI - The dynamic changes of circulating OCN+ cells versus insulinlike growth factor-I during primary healing of orthognathic surgeries. AB - OBJECTIVE: The objective of this study was to determine the dynamic changes of circulating osteocalcin(+) (OCN(+)) cells and insulinlike growth factor-I (IGF-I) in peripheral blood during early primary repair of jaw bones in patients with orthognathic surgery. STUDY DESIGN: The expression of bone-related genes was detected by RT-PCR in circulating OCN(+) cells. The numbers of OCN(+) cells and serum level of IGF-I were determined by flow cytometry, immunocytochemical staining, and ELISA. RESULTS: OCN(+) cells significantly increased in peripheral blood, and reached the peak at 1 to 2 weeks after surgery (P < .05). IGF-I in patients significantly decreased 1 week after surgery (P < .05), and then returned gradually to the normal level. There was no significant correlation between the number of circulating OCN(+) cells and the level of IGF-I (P > .05). CONCLUSIONS: These findings suggested that circulating OCN(+) cells, at least in part, could be mobilized in response to bone injury, and contribute to bone repair in patients with orthognathic surgery. PMID- 22677020 TI - Evaluation of lateral thermal damage and reepithelialization of incisional wounds created by CO2-laser, monopolar electrosurgery, and radiosurgery: a pilot study on porcine oral mucosa. AB - OBJECTIVE: This study aims to compare lateral thermal damage (LTD) produced by CO(2)-laser, monopolar electrosurgery (MES), and radiosurgery (MRS) and its effects on the reepithelialization of oral mucosa incisional wounds. STUDY DESIGN: Five adult swine were submitted to standardized incisions at the tongue and gingiva by MES, MRS, CO(2)-laser and scalpel. Full-thickness specimens were harvested sequentially on days 1 and 3. All specimens were formalin fixed, paraffin embedded, cut, and stained with hematoxylin-eosin to quantify LTD extent. Sections of day 3 were stained for Ki-67 to assess epithelial proliferation at the incision margins. A multiple linear regression model and an analysis of variance were used to determine the correlation of each instrument with LTD extent and Ki-67 expression respectively. RESULTS: LTD was most extensive in the CO(2)-laser but did not differ between the MES and MRS groups. No statistically significant differences regarding reepithelialization were noted among the investigated instruments. CONCLUSIONS: CO(2)-laser produced more extensive LTD, without evident impact on reepithelialization. PMID- 22677021 TI - Primary stability of orthodontic mini-implants inserted into maxilla and mandible of swine. AB - OBJECTIVE: The objective of this study was to assess the primary stability of different orthodontic mini-implants inserted into different maxillary and mandibular regions of swine. MATERIAL AND METHODS: One hundred eighty orthodontic mini-implants produced by 5 different manufacturers, all presenting several shapes, were divided into 5 groups: Mondeal (M), Neodent (N), SIN (S), INP, and Titanium Fix (T). Fifteen pigs (Sus scrofa piau) were used for study and 12 mini implants were inserted into 3 mandibular and maxillary regions. After insertion, the animals were killed and osseous blocks containing the mini-implants were obtained for mechanical pullout tests to be performed by a universal test machine at cross-head speed of 0.5 mm/s. Maximum force values (N/cm) for insertion were recorded and submitted to both analysis of variance and Tukey's test. RESULTS: The primary stability provided by cylindrical mini-implants (groups M and I) was statistically significantly superior to that of conical mini-implants (groups N and S). On the other hand, screw-type mini-implants were shown to be statistically inferior compared with the others (P < .05). Statistical differences between pullout forces at different oral cavity regions were also found (P < .05). The mini-implants inserted into palatal suture had lesser stability, whereas those inserted into upper molar and premolar regions were shown to be more stable. CONCLUSIONS: The shape of mini-implants, in association with location of insertion, is directly related to primary stability. PMID- 22677022 TI - Ophthalmologic complications after intraoral local anesthesia: case report and review of literature. AB - Intraoral administration of local anesthetics is one of the most common dental procedures. Ophthalmologic complications can occur after maxillary as well as mandibular local anesthetic injections and may be underreported and sometimes misinterpreted. A review of the literature from the years 1936-2011 shows 131 cases with this type of complication. This case report presents a patient with right lateral rectus muscle palsy and blurred vision after bimaxillary anesthesia. Signs, symptoms, and pathophysiologic hypotheses of these complications are presented. PMID- 22677023 TI - Role of intra-articular ozone gas injection in the management of internal derangement of the temporomandibular joint. AB - OBJECTIVES: This study was carried out to compare intra-articular ozone gas injection and drug therapy as conservative treatment modalities for internal derangement of the temporomandibular joint (TMJ). STUDY DESIGN: Sixty patients (49 female and 11 male) with bilateral internal derangement of the TMJs, disc displacement with reduction, were included in this study. They were divided randomly into 2 equal groups. The first group was treated by a direct injection of ozone gas into the superior joint space. Each joint received 2 mL ozone-oxygen mixture (ozone gas concentration 10 MUg/mL). The injections were repeated 2 times per week for 3 weeks. The second group received nonsteroidal antiinflammatory drugs and muscles relaxants. The clinical signs and symptoms before and after the treatment were assessed according to Helkimo's clinical dysfunction index. RESULTS: The results showed that 87% of the patients who received ozone gas injections into the superior joint space (n = 26) either completely recovered (37%; n = 11) or improved (50%; n = 15). In the second group, 33% of the patients who were treated with nonsteroidal antiinflammatory drugs and muscle relaxants (n = 10) showed only an improvement in their clinical dysfunction indexes. CONCLUSIONS: Based on the findings of the present study, we can consider that intra-articular ozone gas injection is a promising new treatment modality for internal derangement of the TMJ. However, further clinical and experimental studies are required to provide direct evidence for its mechanism of action and to substantiate our results. PMID- 22677024 TI - Virtual rounding via videoconference-enabled smartphones: a case for multifacility rounds. AB - Telemedicine is defined as the use of medical information exchanged from one site to another via electronic communications to improve delivery of care. This improvement in delivery of care is evident by more-efficient consults, triaging, and real-time communication between patient and surgeon. Internet-capable smartphones are capable of transferring radiographs and other images. Aziz and Ziccardi in 2009 demonstrated using smartphones for downloading images from the hospital archiving system to the resident's phone and then e-mailing or texting them to the attending for immediate review. Here we build on the work of Aziz and Ziccardi as we describe a novel use of smartphones for virtual rounding between residents and faculty based on improvements in technology, specifically video capability and increased accessibility of compatible devices. PMID- 22677025 TI - A bilateral cervical swelling and it is not a malignancy. AB - BACKGROUND: This case report is about a patient with 2 synchronous bilateral cervical schwannomas. PATIENTS AND METHODS: A 59-year-old white man presented a 6 month history of painless bilateral cervical swelling. Magnetic resonance imaging revealed 2 tumors in the carotid sheath. Both tumors, which derived from the cervical sympathetic chain, were surgically removed. RESULTS: Histopathologically, both tumors were diagnosed as schwannomas. CONCLUSIONS: Commonly, a bilateral cervical swelling is not caused by 2 schwannomas. It is unusual for 2 schwannomas to appear in a patient synchronously without any evidence of neurofibromatosis or schwannomatosis. Differential diagnosis of a bilateral cervical swelling includes malignancy, carotid body tumor, and chronic infection. PMID- 22677026 TI - Impetigo presenting as an acute necrotizing swelling of the lower lip in an adult patient. AB - The authors present an unusual case of an acute swelling of the lower lip and septicemia in a 35-year-old, recent immigrant male arriving from India. The patient presented in our emergency department with a 48-hour history of a worsening, painful swelling of the lower lip. On presentation, he was pyrexial and the lip was found to be acutely inflamed with honey-colored crusting, pustular lesions, and induration . A diagnosis of impetigo leading to necrosis of the lip was established, a rare phenomenon potentially resulting in significant tissue destruction. Appropriate medical management achieved a good outcome and prevented disabling tissue loss of the orofacial region. PMID- 22677027 TI - Development of follicular lymphoma of the cervical lymph nodes in a postoperative patient with tongue cancer. AB - Patients with head and neck squamous cell carcinoma are at an increased risk of developing second malignancies. Most commonly, these second primary malignancies are squamous cell carcinoma of the head and neck region, but also noted are esophageal cancer or lung cancer. Hematologic malignancies are uncommon second malignancies. Diagnosis can be challenging, particularly when a patient suffers metastases of squamous cell carcinoma to the cervical lymph nodes in addition to synchronous or metachronous malignant lymphoma that originates in the cervical lymph nodes. This article describes a case of primary follicular lymphoma in the cervical region that was discovered during a postoperative follow-up after partial glossectomy and neck dissection for tongue cancer. PMID- 22677028 TI - Submandibular gland mucocele associated with a mixed ranula. AB - Mucoceles of the submandibular gland are extremely rare pathologic occurrences that present an investigative and management dilemma owing to their clinical indistinguishability from plunging ranulas. Of the few that have been documented, these mucous extravasation cysts involved the submandibular gland alone. We describe perhaps the first case of an extensive submandibular gland mucocele occurring in conjunction with a mixed ranula from the ipsilateral sublingual gland, and discuss the various considerations in the management of such lesions. PMID- 22677029 TI - A SAR study on a series of synthetic lipophilic chalcones as inhibitor of transcription factor NF-kappaB. AB - To define the structural features responsible for the activity of 2,4-dihydroxy-6 isopentyloxychalcone, a newly established inhibitor of LPS induced NF-kappaB activation (IC(50) = 10 MUM), a series of its analogues was prepared and studied for their in vitro activities against LPS induced NF-kappaB inhibition in RAW 264.7 cells. Among the synthesized derivatives, (E)-1-(2-(decyloxy)-6 hydroxyphenyl)-3-(4-hydroxyphenyl)prop-2-en-1-one (IC(50) = 2.7 MUM) and (E)-1-(2 hydroxy-6-(tetradecyloxy)phenyl)-3-(4-hydroxyphenyl)prop-2-en-1-one (IC(50) = 4.2 MUM) showed the most potent inhibition. The SAR studies confirmed that the length (C(8)-C(14)) and C-6 position of linear alkyl chain of ring A is an important factor for the inhibitory activity. Hydroxyl group and its location at 4-position on ring B is also important for the inhibition. The alpha,beta-unsaturated ketone moiety appears as a crucial motif of chalcones for the activity. PMID- 22677030 TI - New chromene scaffolds for adenosine A(2A) receptors: synthesis, pharmacology and structure-activity relationships. AB - In silico screening of a collection of 1584 academic compounds identified a small molecule hit for the human adenosine A(2A) receptor (pK(i) = 6.2) containing a novel chromene scaffold (3a). To explore the structure-activity relationships of this new chemical series for adenosine receptors, a focused library of 43 2H chromene-3-carboxamide derivatives was synthesized and tested in radioligand binding assays at human adenosine A(1), A(2A), A(2B) and A(3) receptors. The series was found to be enriched with bioactive compounds for adenosine receptors, with 14 molecules showing submicromolar affinity (pK(i) >= 6.0) for at least one adenosine receptor subtype. These results provide evidence that the chromene scaffold, a core structure present in natural products from a wide variety of plants, vegetables, and fruits, constitutes a valuable source for novel therapeutic agents. PMID- 22677031 TI - Synthesis and biological activity assays of some new N1-(flavon-7-yl)amidrazone derivatives and related congeners. AB - A series of new N1-(flavon-7-yl)amidrazones incorporating N-piperazines and related congeners were synthesized by reacting the hydrazonoyl chloride derived from 7-aminoflavone and 7-amino-2-methylchromen-4-one with the appropriate piperazine. The chemical structures of the newly prepared compounds were confirmed by elemental analyses, (1)H NMR, (13)C NMR, and ESI-HRMS spectral data. The antitumor activity of these compounds was evaluated on breast cancer (MCF-7 and T47D) and Leukemic (K562) cell lines by a cell viability assay utilizing the tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Although with varying degrees, a significant growth inhibitory and cytotoxic effect was observed on all three cancer cell lines. Among the compounds tested compounds, 5a, 15a, and 18b, were the most active against T47D cell line with IC(50) values of 1.42, 1.92, and 2.92 MUM, respectively. By using other cancer cell lines and with further characterization of their biological mechanism of action, these compounds could prove to be useful candidates as anticancer drugs. PMID- 22677033 TI - Compromised function in the Na(v)1.2 Dravet syndrome mutation R1312T. AB - Ion channels, specifically voltage-gated sodium channels (Na(v)s), are common culprits in inheritable seizure disorders. Some Na(v) isoforms are particularly susceptible, while others are only weakly associated with neuronal hyperexcitability. Representative of the latter group is Na(v)1.2 (gene name SCN2A): despite its abundance in the brain, Na(v)1.2-related epilepsy is rare and only few studies have been conducted as to the pathophysiological basis of Na(v)1.2 in neuronal hyperexcitability. We here present a detailed functional analysis of Na(v)1.2 mutant, R1312T, which was originally found in a child with Dravet syndrome (formerly known as severe myoclonic epilepsy of infancy or SMEI). Whole-cell voltage clamp analysis revealed clearly compromised function: the mutant channels fast- and slow-inactivated at markedly more negative potentials and recovered from fast inactivation more slowly, which resulted in a use dependent current reduction to less than 50% of wildtype levels. We also noted a small hyperpolarizing shift in the voltage dependence of activation. Our findings expand the spectrum of abnormal Na(v) channel behavior in epilepsy and raise the question as to how loss-of-function in a sodium channel predominantly expressed in excitatory neurons can lead to hyperexcitability. PMID- 22677032 TI - Pyramidal cells accumulate chloride at seizure onset. AB - Seizures are thought to originate from a failure of inhibition to quell hyperactive neural circuits, but the nature of this failure remains unknown. Here we combine high-speed two-photon imaging with electrophysiological recordings to directly evaluate the interaction between populations of interneurons and principal cells during the onset of seizure-like activity in mouse hippocampal slices. Both calcium imaging and dual patch clamp recordings reveal that in vitro seizure-like events (SLEs) are preceded by pre-ictal bursts of activity in which interneurons predominate. Corresponding changes in intracellular chloride concentration were observed in pyramidal cells using the chloride indicator Clomeleon. These changes were measurable at SLE onset and became very large during the SLE. Pharmacological manipulation of GABAergic transmission, either by blocking GABA(A) receptors or by hyperpolarizing the GABA(A) reversal potential, converted SLEs to short interictal-like bursts. Together, our results support a model in which pre-ictal GABA(A) receptor-mediated chloride influx shifts E(GABA) to produce a positive feedback loop that contributes to the initiation of seizure activity. PMID- 22677034 TI - The nigrostriatal system in the presymptomatic and symptomatic stages in the MPTP monkey model: a PET, histological and biochemical study. AB - Parkinson's disease (PD) is diagnosed when striatal dopamine (DA) loss exceeds a certain threshold and the cardinal motor features become apparent. The presymptomatic compensatory mechanisms underlying the lack of motor manifestations despite progressive striatal depletion are not well understood. Most animal models of PD involve the induction of a severe dopaminergic deficit in an acute manner, which departs from the typical, chronic evolution of PD in humans. We have used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administered to monkeys via a slow intoxication protocol to produce a more gradual development of nigral lesion. Twelve control and 38 MPTP-intoxicated monkeys were divided into four groups. The latter included monkeys who were always asymptomatic, monkeys who recovered after showing mild parkinsonian signs, and monkeys with stable, moderate and severe parkinsonism. We found a close correlation between cell loss in the substantia nigra pars compacta (SNc) and striatal dopaminergic depletion and the four motor states. There was an overall negative correlation between the degree of parkinsonism (Kurlan scale) and in vivo PET ((18)F-DOPA K(i) and (11)C-DTBZ binding potential), as well as with TH immunoreactive cell counts in SNc, striatal dopaminergic markers (TH, DAT and VMAT2) and striatal DA concentration. This intoxication protocol permits to establish a critical threshold of SNc cell loss and dopaminergic innervation distinguishing between the asymptomatic and symptomatic parkinsonian stages. Compensatory changes in nigrostriatal dopaminergic activity occurred in the recovered and parkinsonian monkeys when DA depletion was at least 88% of control, and accordingly may be considered too late to explain compensatory mechanisms in the early asymptomatic period. Our findings suggest the need for further exploration of the role of non-striatal mechanisms in PD prior to the development of motor features. PMID- 22677035 TI - Discordant phenotype in monozygotic twins with mosaic trisomy 12p in lymphocytes. AB - We report on monochorionic diamniotic male twins discordant for the trisomy 12p syndrome. Trisomy 12p mosaicism with a supernumerary der(12)(pter > q12) was detected in approximately 50% of lymphocytes in both children. Fluorescence in situ hybridisation (FISH) revealed a high grade mosaicism of approximately 77% trisomy 12p cells in buccal smear and 85% in hair follicles in the affected twin, while in the normal developing brother an additional 12p chromosome fragment could not be detected in those tissues. Instead, in 3% of buccal smear and hair follicle cells a minute supernumerary marker chromosome comprising central portions of chromosome 12 was observed. Trisomy 12p mosaicism, confined to the lymphocytes of the unaffected twin, may be due to prenatal twin-to-twin transfusion, explaining the conspicuously discordant clinical phenotype. We discuss the possible sequence of events leading to the cytogenetic findings and compare the clinical phenotype presented in the affected twin with other cases of trisomy 12p and tetrasomy 12p (Pallister-Killian syndrome). PMID- 22677036 TI - Seasonal variation of natural mortality factors of the guava psyllid Triozoida limbata. AB - It is important to understand how components of the agroecosystem interfere with the attack of a pest species and their seasonality in order to use these components in IPM programs. This study focused on the evaluation of the seasonality of natural control factors associated with the guava psyllid Triozoida limbata (Enderlein) in Brazil. Life-table data were collected from an experimental guava orchard during four periods that roughly represented four seasons. Natural mortality was monitored daily through the immature stages, and the relative importance of each natural mortality factor and its seasonality was determined. Significant statistical differences were observed in the mortality during the four periods (P < 0.05). Several factors contributed to the mortality of T. limbata, including rainfall, physiological disturbance, the parasitoid Psyllaephagus sp. (Hymenoptera: Encyrtidae) and specific predators: syrphids, predatory wasps and other generalist predators. Depending on the location of nymphs (exposed or inside galls), the relative importance of the different natural mortality factors changed. The principal component analysis (PCA) showed some trends in the relationship of natural control agents and weather conditions. For example, the occurrence of predatory wasps was positively correlated with temperature and occurrence of winds; the occurrence of syrphids and Psyllaephagus sp. were negatively correlated with temperature and winds; and the occurrence of other generalist predators were negatively correlated with the occurrence of rainfall and photoperiod. The results showed the importance of natural mortality factors for the management of T. limbata and their changes through the different seasons which should be considered when implementing IPM programs in guava orchards. PMID- 22677037 TI - Prospective evaluation of patient-reported quality-of-life outcomes following SBRT +/- cetuximab for locally-recurrent, previously-irradiated head and neck cancer. AB - PURPOSE: Stereotactic body radiotherapy (SBRT) has emerged as a promising salvage strategy for unresectable, previously-irradiated recurrent squamous cell carcinomas of the head and neck (rSCCHN). Here-in, we report the first prospective evaluation of patient-reported quality-of-life (PR-QoL) following re irradiation with SBRT+/-cetuximab for rSCCHN. MATERIALS AND METHODS: From November 2004 to May 2011, 150 patients with unresectable, rSCCHN in a previously irradiated field receiving >40 Gy were treated with SBRT to 40-50 Gy in 5 fractions +/- concurrent cetuximab. PR-QoL was prospectively acquired using the University of Washington Quality-of-Life Revised (UW-QoL-R). RESULTS: Overall PR QoL, health-related PR-QoL, and select domains commonly affected by re irradiation progressively increase following an initial 1-month decline with statistically significant improvements noted in swallowing (p=0.025), speech (p=0.017), saliva (p=0.041), activity (p=0.032) and recreation (p=0.039). CONCLUSIONS: Especially for patients surviving >1-year, improved tumor control associated with SBRT re-irradiation may ameliorate decreased PR-QoL resulting from rSCCHN. These improvements in PR-QoL transcend all measured domains in a validated PR-QoL assessment tool independent of age, use of cetuximab, tumor volume, and interval since prior irradiation. PMID- 22677038 TI - Hypoxia imaging with the nitroimidazole 18F-FAZA PET tracer: a comparison with OxyLite, EPR oximetry and 19F-MRI relaxometry. AB - BACKGROUND AND PURPOSE: (18)F-FAZA is a nitroimidazole PET tracer that can provide images of tumor hypoxia. However, it cannot provide absolute pO(2) values. To qualify (18)F-FAZA PET, we compared PET images to pO(2) measured by OxyLite, EPR oximetry and (19)F-MRI. MATERIALS AND METHODS: Male WAG/Rij rats grafted with rhabdomyosarcoma were used. Tumor oxygenation was modified by gas breathing (air or carbogen). The same day of PET acquisition, the pO(2) was measured in the same tumor either by OxyLite probes (measurement at 10 different sites), EPR oximetry using low frequency EPR or (19)F-relaxometry using 15C5 on an 11.7T MR system. RESULTS: There was a good correlation between the results obtained by PET and EPR (R = 0.93). In the case of OxyLite, although a weaker correlation was observed (R = 0.55), the trend for two values to agree was still related to the inverse function theoretically predicted. For the comparison of (18)F-FAZA PET and (19)F-MRI, no change in T(1) was observed. CONCLUSIONS: A clear correlation between (18)F-FAZA PET image intensities and tumor oxygenation was demonstrated, suggesting that (18)F-FAZA PET is a promising imaging technique to guide cancer therapy. PMID- 22677039 TI - A comparison of tumor motion characteristics between early stage and locally advanced stage lung cancers. AB - PURPOSE: With the increasing use of conformal radiation therapy methods for non small cell lung cancer (NSCLC), it is necessary to accurately determine respiratory-induced tumor motion. The purpose of this study is to analyze and compare the motion characteristics of early and locally advanced stage NSCLC tumors in a large population and correlate tumor motion with position, volume, and diaphragm motion. METHODS AND MATERIALS: A total of 191 (94 early stage, 97 locally advanced) non-small cell lung tumors were analyzed for this study. Each patient received a four-dimensional CT scan prior to receiving radiation treatment. A soft-tissue-based rigid registration algorithm was used to track the tumor motion. Tumor volumes were determined based on the gross tumor volume delineated by physicians in the end of expiration phase. Tumor motion characteristics were correlated with their standardized tumor locations, lobe location, and clinical staging. Diaphragm motion was calculated by subtracting the diaphragm location between the expiration and the inspiration phases. RESULTS: Median, max, and 95th percentile of tumor motion for early stage tumors were 5.9 mm, 31.0 mm, and 20.0 mm, which were 1.2 mm, 12 mm, and 7 mm more than those in locally advanced NSCLC, respectively. The range of motion at 95th percentile is more than 50% larger in early stage lung cancer group than in the locally advanced lung cancer group. Early stage tumors in the lower lobe showed the largest motion with a median motion of 9.2mm, while upper/mid-lobe tumors exhibited a median motion of 3.3mm. Tumor volumes were not correlated with motion. CONCLUSION: The range of tumor motion differs depending on tumor location and staging of NSCLC. Early stage tumors are more mobile than locally advanced stage NSCLC. These factors should be considered for general motion management strategies when 4D simulation is not performed on individual basis. PMID- 22677040 TI - Morphological phenotypes of olfactory ensheathing cells display different migratory responses upon Slit-2. AB - Olfactory ensheathing cells (OECs) are a type of glial cells with morphological plasticity in the olfactory system. Cultured OECs display the process-bearing and flattened shape. Our previous studies have shown that the frontal application of Slit-2 gradient induced the collapse of leading front, and reversed the soma translocation of process-bearing OECs. However, the migratory properties of flattened OECs upon Slit-2 gradient remain elusive. Here, we found that Slit-2 gradient induced the collapse of their plasma membrane, and inhibited migration of flattened OECs. Upon to Slit-2 gradient, the leading front of flattened type 1 OECs firstly showed collapse and retraction, then gradually re-grew a new lamellipodia, finally, showed collapse again (this phenomenon was called as adaptation), while flattened type 2 OECs only showed collapse of plasma membrane. These different migratory responses upon Slit-2 stimulation were possibly due to their different sub-cellular distribution of Robo receptor. Furthermore, F-actin at the peripheral region of leading front was more sensitive to the Slit-2 stimulation than microtubules and the loss of F-actin might be implicated in initiating the collapse of flattened OECs. Finally, the adaptation of flattened type 1 OECs induced by Slit-2 was independent on protein synthesis. Taken together, these results demonstrate that morphological phenotypes of OECs display different migratory properties upon Slit-2 and an unexpected finding that the protein synthesis-independent adaptation in OECs induced by Slit-2. PMID- 22677041 TI - Human Nanog pseudogene8 promotes the proliferation of gastrointestinal cancer cells. AB - There is emerging evidence that human solid tumor cells originate from cancer stem cells (CSCs). In cancer cell lines, tumor-initiating CSCs are mainly found in the side population (SP) that has the capacity to extrude dyes such as Hoechst 33342. We found that Nanog is expressed specifically in SP cells of human gastrointestinal (GI) cancer cells. Nucleotide sequencing revealed that NanogP8 but not Nanog was expressed in GI cancer cells. Transfection of NanogP8 into GI cancer cell lines promoted cell proliferation, while its inhibition by anti-Nanog siRNA suppressed the proliferation. Immunohistochemical staining of primary GI cancer tissues revealed NanogP8 protein to be strongly expressed in 3 out of 60 cases. In these cases, NanogP8 was found especially in an infiltrative part of the tumor, in proliferating cells with Ki67 expression. These data suggest that NanogP8 is involved in GI cancer development in a fraction of patients, in whom it presumably acts by supporting CSC proliferation. PMID- 22677042 TI - MiR-222 modulates multidrug resistance in human colorectal carcinoma by down regulating ADAM-17. AB - Colorectal carcinoma is a frequent cause of cancer-related death in men and women throughout the world. MicroRNAs are endogenous small noncoding RNAs that negatively regulate gene expression at the posttranscriptional level. We investigated the role of ADAM-17 (a desintegrin and metalloproteases 17) as a novel multidrug resistance (MDR) mechanism in multidrug-resistant colorectal carcinoma (CRC) and the role of miR-222 in the development of MDR in CRC cells. We found that the high expression of ADAM-17, which results in growth factor shedding and growth factor receptor activation could induce drug resistance in CRC. Pharmacological inhibition of ADAM-17, in conjunction with chemotherapy, may have therapeutic potential for the treatment of CRC. ADAM-17 is a predicted target of miR-222, which was downregulated in multidrug-resistant CRC cells. The presence of miR-222 was consistently inversely proportionate to the expression levels of ADAM-17. We found that elevated levels of miR-222 in the mimics transfected HCT116/L-OHP and HCT-8/VCR cells reduced the ADAM-17 protein level and the luciferase activity of an ADAM-17 3' untranslated region-based reporter and sensitized these cells' apoptosis to some anticancer drugs. Our findings suggest that miR-222 could play a role in the development of MDR by modulation of ADAM-17, the new MDR treatment target in colorectal carcinoma cells. PMID- 22677043 TI - The pyrimidine nucleotide carrier PNC1 and mitochondrial trafficking of thymidine phosphates in cultured human cells. AB - In cycling cells cytosolic de novo synthesis of deoxynucleotides is the main source of precursors for mitochondrial (mt) DNA synthesis. The transfer of deoxynucleotides across the inner mt membrane requires protein carriers. PNC1, a SLC25 family member, exchanges pyrimidine nucleoside triphosphates in liposomes and its downregulation decreases mtUTP concentration in cultured cells. By an isotope-flow protocol we confirmed transport of uridine nucleotides by PNC1 in intact cultured cells and investigated PNC1 involvement in the mt trafficking of thymidine phosphates. Key features of our approach were the manipulation of PNC1 expression by RNA interference or inducible overexpression, the employment of cells proficient or deficient for cytosolic thymidine kinase (TK1) to distinguish the direction of flow of thymidine nucleotides across the mt membrane during short pulses with [(3)H]-thymidine, the determination of mtdTTP specific radioactivity to quantitate the rate of mtdTTP export to the cytoplasm. Downregulation of PNC1 in TK1(-) cells increased labeled dTTP in mitochondria due to a reduced rate of export. Overexpression of PNC1 in TK1(+) cells increased mtdTTP pool size and radioactivity, suggesting an involvement in the import of thymidine phosphates. Thus PNC1 is a component of the network regulating the mtdTTP pool in human cells. PMID- 22677044 TI - Effect of fibrin glue as an adjuvant to hang-back surgery. AB - BACKGROUND: The hang-back surgery is a useful technique in the field of strabismus surgery. The aim of this study is to determine the stabilizing effects of fibrin glue as an adjuvant to hang-back surgery. MATERIALS AND METHODS: Four (4)-mm hang-back recessions of the superior rectus muscle was performed in 32 eyes of 16 rabbits. Only in the left eye of the 16 rabbits, fibrin glue was applied between the recessed muscle bed and the sclera at the end of hang-back surgery (fibrin glue group). After 6 weeks, we compared the stability of the recessed rectus muscle between the fibrin glue group and the control group by evaluating the displacement of the muscle. RESULTS: The frequency of stable insertion of the recessed muscle at the intended site was greater in the fibrin glue group (9 eyes) compared to the control group (3 eyes) (p=0.028). In the control group, 5 eyes showed anterior displacement and 8 eyes showed posterior displacement and in the fibrin glue group, 1 eye showed anterior displacement, and 6 eyes showed posterior displacement. Anterior displacement was more common in the control group (6.3% Vs 31.3%). The control group and the fibrin glue group showed similar histological findings on microscopic examination. CONCLUSIONS: Fibrin glue is effective in stabilizing the new rectus muscle insertion and decreasing the displacement in the hang-back surgery. PMID- 22677045 TI - IL-17A is essential for cell activation and inflammatory gene circuits in subjects with psoriasis. AB - BACKGROUND: In subjects with psoriasis, inflammation and epidermal hyperplasia are thought to be controlled by T cell-derived cytokines. Evidence suggests that the T(H)17 cell cytokine IL-17A (IL-17) might play a role in disease pathogenesis. OBJECTIVE: We sought to understand the effect that neutralization of IL-17 has on the clinical features of psoriasis and to understand the role that IL-17 has in inflammatory pathways underlying psoriasis in human subjects. METHODS: We examined skin lesions obtained from 40 subjects participating in a phase I, randomized, double-blind, placebo-controlled trial of the anti-IL-17 mAb ixekizumab (previously LY2439821) in which subjects received 5, 15, 50, or 150 mg of subcutaneous ixekizumab or placebo at weeks 0, 2, and 4. RESULTS: There were significant dose-dependent reductions from baseline in keratinocyte proliferation, hyperplasia, epidermal thickness, infiltration into the dermis and epidermis by T cells and dendritic cells, and keratinocyte expression of innate defense peptides at 2 weeks. By week 6, the skin appeared normal. Quantitative RT PCR and microarrays revealed an ablation of the disease-defining mRNA expression profile by 2 weeks after the first dose of study drug. The effect of IL-17 blockade on expression of genes synergistically regulated by IL-17 and TNF-alpha was of higher magnitude at 2 weeks than in prior studies with TNF-alpha antagonism. CONCLUSION: Our data suggest that IL-17 is a key "driver" cytokine that activates pathogenic inflammation in subjects with psoriasis. Neutralizing IL-17 with ixekizumab might be a successful therapeutic strategy in psoriasis. PMID- 22677047 TI - Neuroanatomy of impaired self-awareness in Alzheimer's disease and mild cognitive impairment. AB - INTRODUCTION: Patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) may be unaware of their cognitive impairment. The neuroanatomical mechanisms underlying this symptom, termed anosognosia or impaired self-awareness, are still poorly understood. In the present study we aimed to explore the functional correlates of self-awareness in patients with MCI and AD. METHODS: Fifty-one participants (17 healthy elderly, 17 patients with MCI, and 17 patients with AD), each accompanied by a study partner, took part in a functional magnetic resonance imaging (fMRI) study, in which they were presented with questions regarding themselves (Self condition) or their study partner (Other condition). The study partner was asked to complete a paper questionnaire answering the same questions so the responses of participant and study partner could be compared and "discrepancy" scores calculated for each of the 2 conditions (Self and Other). RESULTS: Behavioural results showed that AD patients had significantly higher "Self discrepancy scores" than controls and MCI patients, whereas there were no significant differences between groups for "Other discrepancy scores". Imaging results showed a significant group-by-condition interaction in brain activation in medial prefrontal and anterior temporal regions, with AD patients showing significantly decreased activation in these regions only for the Self condition. There were no significant differences between Self and Other conditions in either control or MCI groups, suggesting that, in these groups, Self- and Other-appraisal share similar neuroanatomical substrates. CONCLUSIONS: Decreased functional activation of medial prefrontal and anterior temporal cortices is associated with impaired self-awareness in AD patients. This dysfunction, which is specific for Self- but not for Other appraisal, may be a contributing factor to anosognosia in AD. PMID- 22677046 TI - Epigenetic modifications and improved regulatory T-cell function in subjects undergoing dual sublingual immunotherapy. AB - BACKGROUND: Allergen-specific immunotherapy is the only mode of therapy that has been demonstrated to offer a cure in patients with IgE-mediated respiratory allergies. OBJECTIVE: We sought to demonstrate the safety and efficacy of timothy grass (TG) and dust mite (DM) dual sublingual immunotherapy (SLIT) and to begin to investigate the immune mechanisms involved in successful immunotherapy with multiple allergens. METHODS: The safety and efficacy of dual SLIT with TG and DM in children and adults with demonstrated allergies to TG and DM were investigated in a single-center, randomized, double-blind, controlled phase I study. Thirty subjects received either TG and DM dual SLIT (n= 20) or placebo (n = 10). Immune parameters were evaluated for differentiation of desensitized subjects from control subjects. RESULTS: Subjects treated with dual SLIT had decreased rhinoconjunctivitis scores (P < .001) and medication use scores (P < .001) and reduced responses to TG and DM allergen based on results of skin prick tests or nasal disk challenges (P < .01 and P < .001, respectively) compared with placebo treated control subjects. An increase in TG- and DM-specific IgG(4) levels, reduced allergen-specific IgE levels, and subsequent basophil activation were observed in the active treatment group. Dual SLIT promoted allergen-specific suppressive CD4(+)CD25(high)CD127(low)CD45RO(+) forkhead box protein 3 (Foxp3)(+) memory regulatory T cells with reduced DNA methylation of CpG sites within the Foxp3 locus. CONCLUSION: The results of this pilot study suggest that dual SLIT could be an effective means to treat subjects with sensitivities to a variety of allergens and that long-term tolerance might be induced by epigenetic modifications of Foxp3 in memory regulatory T cells. PMID- 22677049 TI - [Prevalence of malnutrition in Spanish elders: systematic review]. AB - Over the past years, several studies have examined the prevalence of malnutrition. The purpose of the present systematic literature review is to provide an overview of the current knowledge about the nutritional situation of elderly. Based on a literature research, studies with information about the prevalence of malnutrition published between 1995 and 2011 were considered. A total of 43,235 participants from 47 eligible studies were found. According to the Mini Nutritional Assessment, malnutrition was observed in 16.6% (95% confidence interval [95% CI] 0-62); according to anthropometric and biochemical parameters, malnutrition was observed in 21.4% (95% CI 2-77.3) and, when other nutritional indexes were used, malnutrition was observed in 47.3% (95% CI 10.6 94.7). Prevalence rates of malnutrition were highest in studies with a high proportion of patient who were severely disabled, had hip fracture or swallowing problems. It can be concluded that malnutrition is generally widespread and is highly variable, according to parameters used for nutritional assessment, health related problems or the population under study. Future studies should use standardized nutritional assessment tools in order to improve the prognosis of malnutrition in the elderly and achieve better comparability of study results. PMID- 22677048 TI - [Update in hereditary angioedema due to C1 inhibitor deficiency]. PMID- 22677050 TI - Systematic interaction analysis of human lipocalin-type prostaglandin D synthase with small lipophilic ligands. AB - L-PGDS [lipocalin-type PG (prostaglandin) D synthase] is a multi-functional protein, acting as a PGD2-producing enzyme and a lipid-transporter. In the present study, we focus on the function of L-PGDS as an extracellular transporter for small lipophilic molecules. We characterize the binding mechanism of human L PGDS for the molecules, especially binding affinity stoichiometry and driving force, using tryptophan fluorescence quenching, ICD (induced circular dichroism) and ITC (isothermal titration calorimetry). The tryptophan fluorescence quenching measurements revealed that haem metabolites such as haemin, biliverdin and bilirubin bind to L-PGDS with significantly higher affinities than the other small lipophilic ligands examined, showing dissociation constant (K(d)) values from 17.0 to 20.9 nM. We focused particularly on the extra-specificities of haem metabolites and L-PGDS. The ITC and ICD data revealed that two molecules of the haem metabolites bind to L-PGDS with high and low affinities, showing K(d) values from 2.8 to 18.1 nM and from 0.209 to 1.63 MUM respectively. The thermodynamic parameters for the interactions revealed that the contributions of enthalpy and entropy change were considerably different for each haem metabolite even when the Gibbs energy change was the same. Thus we believe that the binding energy of haem metabolites to L-PGDS is optimized by balancing enthalpy and entropy change. PMID- 22677051 TI - Optimization and characterization of chromium(VI) reduction in saline condition by moderately halophilic Vigribacillus sp. isolated from mangrove soil of Bhitarkanika, India. AB - A Gram-positive moderately halophilic Cr(VI) tolerant bacterial strain H4, isolated from saline mangrove soil, was identified as Vigribacillus sp. by biochemical characterization and 16S rRNA analysis. In LB medium, the strain could tolerate up to 1000 mg L(-1) Cr(VI) concentration and reduced 90.2 and 99.2% of 100 mg L(-1) Cr(VI) under optimized set of condition within 70 h in absence and presence of 6 wt.% NaCl, respectively. The fitting of time course reduction data to an exponential rate equation yielded the Cr(VI) reduction rate constants in the range (0.69-5.56)*10(-2)h(-1). Analyses of total chromium and bacterial cell associated with reduced product by AAS, SEM/EDS, TEM/SAED, FT-IR and UV-vis-DRS indicated the formation of about 35% of insoluble Cr(III) either as Cr(OH)(3) precipitate in nanometric size or immobilized on the bacterial cell surface while the remaining 65% of reduced chromium was present as soluble Cr(III) in the growth medium. Powder XRD analysis revealed the amorphous nature of the precipitated Cr(OH)(3). The high Cr(VI) reducing ability of the strain under saline condition suggests the Vigribacillus sp. as a new and efficient strain capable of remediating highly saline Cr(VI) polluted industrial effluents. PMID- 22677052 TI - Removal of bacterial pathogen from wastewater using Al filter with Ag-containing nanocomposite film by in situ dispersion involving polyol process. AB - In this study, a filter with deposited Ag/Al(OH)(3) mesoporous nanocomposite film was fabricated to remove bacterial pathogens from wastewater. Mesoporous Al(OH)(3) film was generated on the Al foam body by alkali surface modification, followed by immersion in a polyol solution for 4h at an elevated temperature in order to deposit silver nanoparticles (Ag NPs). The Al(OH)(3) porous matrix showed a significant increase in specific surface area due to the large size of the voids between flakes, which reached several tens of nanometers. After in situ three-dimensional deposition of Ag NPs by a polyol process, the Ag NPs were nucleated and grown at the surface of the mesoporous Al(OH)(3) film. The filter with Ag/Al(OH)(3) mesoporous nanocomposite film showed a good bacterial pathogen removal rate within a very short contact time compared to the untreated Al foam filter. Filters with deposited Ag/Al(OH)(3) mesoporous nanocomposite film have great potential for application as antimicrobial filters for tap water purification, wastewater treatment, and other bio-related applications. PMID- 22677053 TI - Identification of multi-level toxicity of liquid crystal display wastewater toward Daphnia magna and Moina macrocopa. AB - Toxicity-based regulations of industrial effluent have been adopted to complement the conventional discharge limits based on chemical analyses. In this study, multi-level toxicity including acute toxicity, feeding rate inhibition and oxidative stress of effluent from a liquid crystal display (LCD) wastewater treatment plant (WWTP) to Daphnia magna (reference species) and Moina macrocopa (native species) were periodically monitored from April 2010 to April 2011. Raw wastewater was acutely toxic to both D. magna and M. macrocopa, but the toxicity reached less than 1 TU in the final effluent (FE) as treatment proceeded. Although acute toxicity was not observed in the FE, the feeding rate of daphnids was significantly inhibited. Additionally, the antioxidant enzyme activity of catalase, superoxide dismutase and glutathione peroxidase (GPx) in D. magna increased significantly when compared to the control, while only GPx activity was increased significantly in M. macrocopa (p<0.05). A toxicity identification evaluation using D. magna showed that Cu was the key toxicant in the FE, which was not effectively removed by the coagulation/flocculation process in the LCD WWTP. In addition, Al originating from the coagulant seemed to increase toxicity of the FE. PMID- 22677054 TI - Enhancement of stabilizing properties of double-base propellants using nano-scale inorganic compounds. AB - The use of inorganic stabilizers for double-base propellants in literature is scanty; therefore five samples (S(1)-S(5)) of different percentages (2-4%) of nano-clinoptilolite were investigated as new inorganic stabilizers for double base propellants (DBPs). The grain size of clinoptilolite stabilizer played an important role in the stabilization effect. As the grain size of stabilizer decreases, the surface area of stabilizer increases and the ability to absorb pronounce amount of hazardous nitrogen oxides increases. In this work clinoptilolite in nano-scale (30 nm) has been used to obtain higher stabilizing effect for DBPs. The evaluation process has been performed through the classical thermal stability tests (Bergmann-Junk and calorimetric tests), in comparison with thermal analyses measurements (TGA and DSC) and kinetic parameters calculation such as activation energy (E(a)), enthalpy of activation (DeltaH*), Gibbs free energy of activation (DeltaG*), entropy of activation (DeltaS*) and frequency factor (A), which calculated using Coats-Redfern and Horowitz-Metzger methods. The results for the new stabilizers were compared with that for the classical one (N,N-diethyldiphenyl urea, C(1)). It has been found that the samples containing new stabilizer with percentages (3.0, 3.5 and 4.0%) showed better stability effect for DBPs than the classical one. The efficiency of stabilization of each inorganic stabilizer to DBPs is also rationalized and correlated with its structure. PMID- 22677055 TI - Loess clay based copolymer for removing Pb(II) ions. AB - Functional monomers, such as acrylic acid and 2-hydroxyethyl methacrylate were supported into loess clay in situ polymerization, which afforded loess clay based copolymer (LC/PAAHM), a new kind of polymer adsorbent for removing Pb(II) ions from aqueous solution. Characterization of the polymer adsorbent was carried out by different sophisticated methods, such as Fourier transformation infrared spectrometry (FTIR), scanning electron microscopy (SEM), X-ray diffractometry (XRD), thermogravimetric analysis (TGA), and Zetasizer. Batch experiments were carried out to evaluate the factors affecting the removal efficiency, in which the pH, the adsorbent dosage, temperature and initial Pb(II) concentration all found in positive relevance to the increase of Pb(II) removal efficiency. The removal rate of Pb(II) got to 99% at room temperature and the adsorption capacity got to 356.9 mg/g. The pseudo-first-order and pseudo-second-order kinetic models were applied to test the experimental data, and Langmuir and Freundlich models have been applied to study the adsorption equilibrium, respectively. PMID- 22677056 TI - Assessing human exposure risk to cadmium through inhalation and seafood consumption. AB - The role of cadmium (Cd) bioaccessibility in risk assessment is less well studied. The aim of this study was to assess human health risk to Cd through inhalation and seafood consumption by incorporating bioaccessibility. The relationships between trophically available Cd and bioaccessibility were constructed based on available experimental data. We estimated Cd concentrations in human urine and blood via daily intake from seafood consumption and inhalation based on a physiologically-based pharmacokinetic (PBPK) model. A Hill-based dose response model was used to assess human renal dysfunction and peripheral arterial disease risks for long-term Cd exposure. Here we showed that fish had higher bioaccessibility (~83.7%) than that of shellfish (~73.2%) for human ingestion. Our results indicated that glomerular and tubular damage among different genders and smokers ranged from 18.03 to 18.18%. Our analysis showed that nonsmokers had 50% probability of peripheral arterial disease level exceeding from 3.28 to 8.80%. Smoking populations had 2-3 folds higher morbidity risk of peripheral arterial disease than those of nonsmokers. Our study concluded that the adverse effects of Cd exposure are exacerbated when high seafood consumption coincides with cigarette smoking. Our work provides a framework that could more accurately address risk dose dependency of Cd hazard. PMID- 22677057 TI - Coming into line: the EU's Court softens on cross-border health care. PMID- 22677058 TI - [The use of sugammadex in a patient with myasthenia gravis]. PMID- 22677059 TI - [Suxamethonium and myotonic dystrophy type 1]. PMID- 22677060 TI - [Ultrasound location of the first rib confirm the level of realization of thoracic paravertebral block]. PMID- 22677061 TI - [Preoperative malnutrition: an underestimated risk factor]. PMID- 22677062 TI - [Porphyromonas causing lung cavitation with empyema]. PMID- 22677063 TI - Water resource management in New Zealand: jobs or algal blooms? AB - New Zealand faces a choice between environmental improvement and dairy industry profitability and employment, since improved water quality in lakes and rivers may require measures that will reduce net farm profit. Environmental valuation studies often consider preferences for employment but rarely focus specifically on the effect of job losses on respondent preferences for environmental improvement. A choice experiment was used to investigate people's willingness to pay for water quality improvements in a typical dairy catchment in the Waikato region of New Zealand. It was found that respondents would be willing to pay for water that is safer for swimming with improvements in clarity and ecological health, but are concerned about job losses, even when they do not expect to be directly affected. This may be explained by the concept of sociality, whereby the influence of direct interpersonal interaction on human behaviour, affects choice behaviour. Findings from this study and ongoing research should allow decision makers to consider both the costs and the benefits of different levels of water quality improvements, so allowing policy makers to identify the most cost effective options for achieving any given improvement in water quality. PMID- 22677064 TI - SPP-3, a saposin-like protein of Caenorhabditis elegans, displays antimicrobial and pore-forming activity and is located in the intestine and in one head neuron. AB - Caenopores belong to the saposin-like protein superfamily in Caenorhabditis elegans with 33 putative antimicrobial and pore-forming proteins. In this study, we analysed one selected member of this multifarious protein family, namely SPP 3, in detail, as its coding gene has been described to be inducible after bacterial challenge. The recombinant protein was antimicrobially active against a wide range of gram-negative and gram-positive bacteria and displayed membrane permeabilizing and pH-dependent pore-forming activity. Promoter activity of the respective gene, spp-3, was localized to the intestine and the head neuron SDQR. While gene silencing had no apparent effect on the number of surviving Escherichia coli bacteria in the intestine, it increased the egg laying significantly. Accordingly, SPP-3 is a protein with antimicrobial activity that is presumably part of the redundant armamentarium of effector proteins in the worm's intestine, may help to protect neurons, and appears to be involved in regulating reproduction. PMID- 22677065 TI - Effect of preservation conditions of collagen substrate on its fibril formation and rabbit chondrocyte morphology. AB - The degree of collagen fibril formation was altered by varying the preservation conditions. The collagen substrate under atmosphere of nitrogen gas for 4 days exhibited well-developed collagen fibril network accompanied with the frequency of round-shaped chondrocyte cells (f(R)) of 0.62, the value of which was slightly lower than that on the reference substrate. The exposure to air and prolongation of preservation led to further degradation of collagen fibril networks accompanied with f(R) lower than 0.4. It was thus demonstrated that the preservation conditions of the collagen substrate influenced the chondrocyte cell morphology. PMID- 22677066 TI - Comparative analysis of cells and proteins of pumpkin plants for the control of fruit size. AB - Common pumpkin plants (Cucurbita maxima) produce fruits of 1-2 kg size on the average, while special varieties of the same species called Atlantic Giant are known to produce a huge fruit up to several hundred kilograms. As an approach to determine the factors controlling the fruit size in C. maxima, we cultivated both AG and control common plants, and found that both the cell number and cell sizes were increased in a large fruit while DNA content of the cell did not change significantly. We also compared protein patterns in the leaves, stems, ripe and young fruits by two-dimensional (2D) gel electrophoresis, and identified those differentially expressed between them with mass spectroscopy. Based on these results, we suggest that factors in photosynthesis such as ribulose-bisphosphate carboxylase, glycolysis pathway enzymes, heat-shock proteins and ATP synthase play positive or negative roles in the growth of a pumpkin fruit. These results provide a step toward the development of plant biotechnology to control fruit size in the future. PMID- 22677067 TI - Vault particles: a new generation of delivery nanodevices. AB - Vault particles possess many attributes that can be exploited in nanobiotechnology, particularly in the creation of drug delivery nanodevices. These include self-assembly, 100 nm size range, a dynamic structure that may be controlled for manipulation of drug release kinetics and natural presence in humans ensuring biocompatibility. The flexibility and the adaptability of this system have been greatly enhanced by the emerging atomic-level information and improved comprehension of vault structure and dynamics. It seems likely that this information will allow their specific tailoring to the individual requirements of each drug and target tissue. These properties provide vaults with an enormous potential as a versatile delivery platform. PMID- 22677068 TI - Simulation of the effects of microtubules in the cortical rotation of amphibian embryos in normal and zero gravity. AB - This paper reports the results of computer modeling of microtubules that end up in the cortical region of a one-cell amphibian embryo, prior to the first cell division. Microtubules are modeled as initially randomly oriented semi-flexible rods, represented by several lines of point-masses interacting with one another like masses on springs with longitudinal and transverse stiffness. They are also considered to be space-filling rods floating in a viscous fluid (cytoplasm) experiencing drag forces and buoyancy from the fluid under a variable gravity field to test gravitational effects. Their randomly distributed interactions with the surrounding spherical container (the cell membrane) have a statistical nonzero average that creates a torque causing a rotational displacement between the cytoplasm and the rigid cortex. The simulation has been done for zero and normal gravity and it validates the observation that cortical rotation occurs in microgravity as well as on Earth. The speed of rotation depends on gravity, but is still substantial in microgravity. PMID- 22677069 TI - Using single protein biomarkers to predict health and disease in diverse patient populations: a new role for assessment of immunoglobulin free light chains. PMID- 22677070 TI - The limits of acceptable biological variation in elite athletes: should sex ambiguity be treated differently from other advantageous genetic traits? PMID- 22677071 TI - Are there alternatives to hemodialysis for the elderly patient with end-stage renal failure? PMID- 22677072 TI - Use of nonclonal serum immunoglobulin free light chains to predict overall survival in the general population. AB - OBJECTIVE: To determine whether the free light chain (FLC) assay provides prognostic information relevant to the general population. METHODS: After excluding persons with a known plasma cell disorder, we studied 15,859 Olmsted County, Minnesota, residents 50 years or older in whom unmasked data and samples for FLC testing were available. Baseline information was obtained between March 13, 1995, and November 21, 2003, and follow-up status and cause of death were identified through June 30, 2009. The kappa and lambda FLC sum (Sigma FLC) was evaluated for its ability to predict overall survival. Specific causes of death were also investigated. RESULTS: In 158,003 person-years of follow-up, 4348 individuals died. A high Sigma FLC was significantly predictive of worse overall survival; the risk ratio for death for those with the highest decile of Sigma FLC (ie, >= 4.72 mg/dL) was 4.4 (95% confidence interval, 4.1-4.7) relative to the remaining study participants. Multivariate analyses demonstrated that this excess risk of death was independent of age, sex, and renal insufficiency, with a corrected risk ratio of 2.1 (95% confidence interval, 1.9-2.2). The increased mortality was not restricted to any particular cause of death because the observed-to-expected risk of death from most causes was significantly higher among those individuals with an antecedent Sigma FLC of 4.72 mg/dL or higher, which is near the upper limit of normal for the test. CONCLUSION: A nonclonal elevation of Sigma FLC is a significant predictor of worse overall survival in the general population of persons without plasma cell disorders. PMID- 22677073 TI - Cardiac channel molecular autopsy: insights from 173 consecutive cases of autopsy negative sudden unexplained death referred for postmortem genetic testing. AB - OBJECTIVE: To perform long QT syndrome and catecholaminergic polymorphic ventricular tachycardia cardiac channel postmortem genetic testing (molecular autopsy) for a large cohort of cases of autopsy-negative sudden unexplained death (SUD). METHODS: From September 1, 1998, through October 31, 2010, 173 cases of SUD (106 males; mean +/- SD age, 18.4 +/- 12.9 years; age range, 1-69 years; 89% white) were referred by medical examiners or coroners for a cardiac channel molecular autopsy. Using polymerase chain reaction, denaturing high-performance liquid chromatography, and DNA sequencing, a comprehensive mutational analysis of the long QT syndrome susceptibility genes (KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2) and a targeted analysis of the catecholaminergic polymorphic ventricular tachycardia type 1-associated gene (RYR2) were conducted. RESULTS: Overall, 45 putative pathogenic mutations absent in 400 to 700 controls were identified in 45 autopsy-negative SUD cases (26.0%). Females had a higher yield (26/67 [38.8%]) than males (19/106 [17.9%]; P<.005). Among SUD cases with exercise-induced death, the yield trended higher among the 1- to 10-year-olds (8/12 [66.7%]) compared with the 11- to 20-year-olds (4/27 [14.8%]; P=.002). In contrast, for those who died during a period of sleep, the 11- to 20-year-olds had a higher yield (9/25 [36.0%]) than the 1- to 10-year-olds (1/24 [4.2%]; P=.01). CONCLUSION: Cardiac channel molecular autopsy should be considered in the evaluation of autopsy negative SUD. Several interesting genotype-phenotype observations may provide insight into the expected yields of postmortem genetic testing for SUD and assist in selecting cases with the greatest potential for mutation discovery and directing genetic testing efforts. PMID- 22677074 TI - The relationship of the intensity of posttreatment prostate-specific antigen surveillance and prostate cancer outcomes: results from a population-based cohort. AB - OBJECTIVE: To determine whether higher intensity of prostate-specific antigen (PSA) surveillance was associated with earlier detection of biochemical recurrence (BCR) or survival. PATIENTS AND METHODS: We identified a population based cohort of 832 men diagnosed with nonmetastatic prostate cancer between January 1, 1995, and July 31, 2006. These men were treated with radical prostatectomy (RP), brachytherapy or external beam radiation therapy (RT), or primary androgen deprivation therapy or chose watchful waiting. To test the associations of intensity in PSA surveillance with study outcomes, we used a 2 year landmark analysis to assess whether the number of PSA tests during the first 2 years after treatment was associated with earlier detection of BCR, prostate cancer-related mortality, and all-cause mortality. We used landmark analysis to assess the association of PSA intensity, adjusting for clinicopathologic covariate, with outcome. RESULTS: Median follow-up time for the entire cohort was 6.7 years. Higher Gleason score was the only clinicopathologic variable associated with higher PSA frequency in multivariable analysis for both the RP and RT groups (P value of .001 and .05, respectively). After adjustment for other covariates, the frequency of PSA tests during the first 2 years after RP did not increase the ability to detect BCR (hazard ratio, 1.00; 95% confidence interval, 0.84-1.19) or all-cause mortality (hazard ratio, 0.95; 95% confidence interval, 0.70-1.30) in the landmark analysis. CONCLUSION: Higher intensity of PSA surveillance during the 2 years after RP or RT did not improve earlier detection of BCR or survival. Evidence-based guidelines for PSA surveillance after primary treatment are needed. PMID- 22677075 TI - Statins in heart failure: the paradox between large randomized clinical trials and real life. AB - OBJECTIVE: To assess the relationship between statins and prognosis in ischemic and nonischemic patients with heart failure (HF) in a real-life cohort followed up for a long period. PATIENTS AND METHODS: This prospective study included 960 patients with HF with preserved or depressed left ventricular ejection fraction (LVEF), irrespective of HF etiology, who were referred to the HF clinic of a university hospital between August 1, 2001, and December 31, 2008. The patients were followed up for a maximum of 9.1 years (median, 3.7 years), and survival in ischemic and nonischemic patients was determined. RESULTS: Median age was 69 years, and median LVEF was 31%. Of the 960 patients, 532 (55.4%) had ischemic HF etiology, and most received angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (846; 88.1%) and beta-blockers (776; 80.8%). Patients with HF of ischemic origin were more often treated with statins (P<.001). During follow-up, 440 patients (45.8%) died. Statin therapy was associated with significantly improved survival (hazard ratio, 0.45 [95% confidence interval, 0.37-0.54]; P<.001). After adjustment for HF prognostic factors (age, sex, cholesterol level, New York Heart Association class, HF etiology, LVEF, body mass index, HF duration, atrial fibrillation, implantable cardioverter-defibrillator therapy, and medicines), statins remained significantly associated with lower mortality risk in both ischemic (P=.007) and nonischemic (P=.002) patients. CONCLUSION: In contrast to results of large randomized trials, statins were independently and significantly associated with lower mortality risk in our real-life HF cohort, including patients with nonischemic HF etiology. PMID- 22677076 TI - Effect of insulin sensitizer therapy on atherothrombotic and inflammatory profiles associated with insulin resistance. AB - OBJECTIVE: To determine whether targeted pharmacological improvement of insulin sensitivity will normalize the associated elevations of thrombotic and inflammatory cardiovascular disease (CVD) biomarkers in individuals with insulin resistance. PATIENTS AND METHODS: Study 1 was a cross-sectional study of Asian Indians with and without diabetes mellitus and Northern European Americans without diabetes (n=14 each) conducted between December 11, 2003, and July 14, 2006. Study 2 was a secondary analysis of a double-blind randomized controlled study conducted between August 19, 2005, and August 24, 2010, that included 25 individuals with untreated diabetes or impaired fasting glucose who were randomized to receive placebo (n=13) or a combination of metformin, 1000 mg twice daily, and pioglitazone, 45 mg daily (n=12), for 3 months. In both studies, measurements of insulin sensitivity (euglycemic-hyperinsulinemic clamp) and plasma inflammatory and thrombotic factor concentrations were obtained on enrollment (studies 1 and 2) and after intervention (study 2). RESULTS: Study 1 demonstrated significant correlations between insulin sensitivity and plasma adiponectin, high-density lipoprotein cholesterol, plasminogen activator inhibitor 1, interleukin 6, tumor necrosis factor alpha, and triglycerides. Insulin sensitizer therapy significantly improved insulin sensitivity, inflammatory cytokines except interleukin 6, and thrombotic factors except fibrinogen, without concomitant changes in weight, blood pressure, or body composition. CONCLUSION: Insulin sensitizer therapy ameliorates inflammatory and thrombotic factors implicated in developing CVD. Interventions to improve insulin sensitivity may thus be considered as therapeutic options to reduce CVD burden in insulin-resistant states, although further research is needed to determine long term effects on morbidity and mortality. PMID- 22677077 TI - Positron emission tomographic scans in lymphoma: convention and controversy. AB - The use of sensitive and specific imaging techniques for accurate initial staging and evaluation of response to therapy in patients with lymphoma is essential for their optimal management. Fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) integrated with computed tomography (CT) has emerged as a powerful imaging tool and is being routinely used in staging, response evaluation, and posttreatment surveillance in patients with non-Hodgkin lymphoma and Hodgkin lymphoma. PET/CT is currently widely used in clinical practice, but the established clinical benefit is currently restricted to the posttreatment evaluation of Hodgkin lymphoma, diffuse large B-cell lymphoma, and follicular lymphoma. Although used in other histologic subtypes and in other clinical situations including response assessment, its impact on patient outcome remains to be demonstrated. We performed a literature search of PubMed from 1999 to 2011 using the following keywords: PET scan, FDG-PET, PET/CT, lymphoma. This review addresses the challenges and controversies in the use of PET/CT scans in the management of patients with lymphoma. PMID- 22677078 TI - Complications associated with use of levamisole-contaminated cocaine: an emerging public health challenge. AB - Levamisole is an immunomodulatory agent that was used to treat various cancers before being withdrawn from the United States market in 2000 because of adverse effects. Levamisole is currently approved as an antihelminthic agent in veterinary medicine, but is also being used illicitly as a cocaine adulterant. Potential complications associated with use of levamisole-laced cocaine include neutropenia, agranulocytosis, arthralgias, retiform purpura, and skin necrosis. Treatment is primarily supportive, and skin lesions typically resolve with cessation of cocaine use. The incidence of hospitalizations related to use of levamisole-contaminated cocaine continues to increase and clinicians should be aware of the more common clinical manifestations. PMID- 22677079 TI - Potential adverse cardiovascular effects from excessive endurance exercise. AB - A routine of regular exercise is highly effective for prevention and treatment of many common chronic diseases and improves cardiovascular (CV) health and longevity. However, long-term excessive endurance exercise may induce pathologic structural remodeling of the heart and large arteries. Emerging data suggest that chronic training for and competing in extreme endurance events such as marathons, ultramarathons, ironman distance triathlons, and very long distance bicycle races, can cause transient acute volume overload of the atria and right ventricle, with transient reductions in right ventricular ejection fraction and elevations of cardiac biomarkers, all of which return to normal within 1 week. Over months to years of repetitive injury, this process, in some individuals, may lead to patchy myocardial fibrosis, particularly in the atria, interventricular septum, and right ventricle, creating a substrate for atrial and ventricular arrhythmias. Additionally, long-term excessive sustained exercise may be associated with coronary artery calcification, diastolic dysfunction, and large artery wall stiffening. However, this concept is still hypothetical and there is some inconsistency in the reported findings. Furthermore, lifelong vigorous exercisers generally have low mortality rates and excellent functional capacity. Notwithstanding, the hypothesis that long-term excessive endurance exercise may induce adverse CV remodeling warrants further investigation to identify at-risk individuals and formulate physical fitness regimens for conferring optimal CV health and longevity. PMID- 22677081 TI - 95-year-old woman with sudden-onset dyspnea. PMID- 22677080 TI - Evaluating the patient with diarrhea: a case-based approach. AB - The evaluation of the patient with diarrhea can be complex and the treatment challenging. In this article, the definition of diarrhea and the pathophysiologic mechanisms that lead to diarrhea are reviewed. A simplified 5-step approach to the patient with diarrhea is provided and applied in a case-oriented manner applicable to everyday clinical practice. On completion of this article, you should be able to (1) define diarrhea, (2) outline various pathophysiologic mechanisms of diarrhea, and (3) describe a simplified 5-step approach to facilitate the evaluation of diarrhea. PMID- 22677083 TI - William Shockley and the transistor. PMID- 22677084 TI - Apicoaortic conduit: a simple solution to a difficult problem. PMID- 22677085 TI - Design-of-experiment strategy for the formulation of laccase biocatalysts and their application to degrade bisphenol A. AB - Immobilizing enzymes can expand their applicability to continuous process operations and facilitates process intensification. An optimized formulation of immobilized biocatalysts is therefore of strategic interest in the field of industrial biotechnology. Nevertheless, biocatalyst formulation still largely relies on empirical approaches which lack effectiveness in the identification of optimum immobilization conditions. In the present study, design of experiments, multiple linear regressions and modeling were used to screen, interpret and finally optimize crucial immobilization parameters. A laccase preparation from Coriolopsis polyzona MUCL38443 was immobilized via a sequential adsorption crosslinking process on mesoporous silica particles. As a target variable, biocatalyst activity was doubled (~280 U g(-1)) while dramatically reducing processing time (two hours instead of 26 hours) and reagent inputs (80 mm instead of 1m glutaraldehyde (GLU)). Immobilization yield (~50%) and thermostability (~60% residual activity after 24 hours at 45 degrees C) could be maintained under the optimized conditions. As an example of its application in environmental biotechnology, the optimized biocatalyst was implemented in a continuous stirred tank membrane reactor (CSTMR) to continuously degrade the endocrine disruptor bisphenol A (BPA) in wastewater. A 90% removal of 50 MUm BPA was achieved over 30 reactor volumes (hydraulic residence time (HRT) of 1.85 hours, 50 mL working volume). PMID- 22677086 TI - Comparison between aerobic and anoxic metabolism of denitrifying-EBPR sludge: effect of biomass poly-hydroxyalkanoates content. AB - Biomass with denitrifying phosphate uptake ability was tested under sequencing anaerobic-aerobic and anaerobic-anoxic conditions. The initial dose of acetate, under anaerobic conditions varied to achieve different PHA (poly hydroxyalkanoates) saturation of PAO (polyphosphate accumulating organisms) cells. Increased acetate dosage under anaerobic conditions led to higher phosphate release and increased PHA storage by PAOs and, also, to greater phosphate uptake rates under the following aerobic and/or anoxic conditions. The experimental results also indicated that when organic carbon is limited under anaerobic conditions, more internal glycogen supplementary to polyphosphate cleavage is utilized by the biomass, resulting in less phosphate release and more PHA stored per acetate taken up. In the subsequent aerobic and/or anoxic phase PAOs demonstrate an improved EBPR (enhanced biological phosphorus removal) performance, with regard to PHA consumption per phosphate taken up, for reduced initial biomass PHA content under both aerobic and anoxic conditions. The examination of EBPR biomass under controlled operational conditions, where experimental analysis of the relevant compounds in the bulk phase (PO(4)(3-), NO(3)(-) and/or O(2)) in conjunction with the biomass intracellular products (PHA, glycogen), contributes to an improved understanding of the PAOs metabolic behavior, with regard to organic substrate availability. PMID- 22677087 TI - [Chronic idiopathic thrombocytopenia outcome during pregnancy (62 cases)]. AB - PURPOSE: The aim of this study was to assess the platelet count outcome during a pregnancy occurring in a series of 62 women followed for a chronic idiopathic thrombocytopenia. METHODS: We studied the medical files of women who had a previous history of chronic idiopathic thrombocytopenia persistently below 150G/L for at least 1 year, and who became pregnant over a 14-year period. RESULTS: Sixty-two pregnancies (including 41 in women suffering from an immune thrombocytopenic purpura according to updated definition criteria) which occurred in 50 women, were analysed. At the beginning of the pregnancy, platelet count was above 150G/L in 16% of the cases and lower than 50G/L in 8%. Platelets decreased by more than 25% for 55% of the pregnancies, remained stable during pregnancy in 33% and improved in 12%. Platelet count remained above 50G/L in 70% of the pregnancies and higher than 100G/L in 27%. Mean nadir was 84G/L at 31 weeks of gestation. A treatment was started in 40% of pregnancies, among them 64% of the cases during the last month only in order to allow locoregional anaesthesia at delivery. Platelet count was below 150G/L at delivery in 82% of the women (116+/ 56G/L). No bleeding occurred in 83% of the pregnancies. Neonatal mean platelet count was 225+/-87G/L, thrombocytopenia occurred in 17% of the babies (platelet count below 150G/L), without any serious bleeding. CONCLUSION: Pregnancy worsens chronic idiopathic thrombocytopenia outcome in half of the cases, most of the time without any haemorrhagic complications. PMID- 22677089 TI - Secular trends in body composition and frequency of overweight and obesity in boys aged 3-18 from Krakow, Poland, within the last 30 years (from 1983 to 2010). AB - The aim of this study was to examine the changes in body composition (fatness and muscle and bone mass) and BMI in three cohorts of boys living in Krakow, Poland, over the last 30 years, and to assess how overweight and obesity frequencies have developed over the period. The anthropological survey was conducted in 2010, and comprised 1863 boys from Krakow aged 3-18 years. The analysis compared the latest measurements of selected skinfold thicknesses, BMI, total body muscle mass and bone mass with the results of surveys from 1983 (N=1934) and 2000 (N=2323). The frequency of overweight and obesity was assessed for the last survey series, and their trends determined for the years 1983-2000 and 2000-2010. The analysis of fat tissue distribution showed that the boys from the 2010 cohort, as compared with those examined in 2000, had a higher trunk adiposity, as manifested by greater thickness of subscapular and suprailiac skinfold thicknesses, and boasted a larger muscle mass and lower bone mass. The survey results also showed that, from 1983 to 2000, the percentage of overweight boys increased slightly (from 11.69% to 12.48%), whereas the frequency of obesity did not change. Over the last decade, the percentage of overweight people has increased to 15.94%, and the frequency of obesity has doubled, equalling 4.94% in 2010. The last decade has seen a minor trend in boys towards increased trunk adiposity, muscle mass, BMI and prevalence of overweight and obesity, and a slight decrease in bone mass. PMID- 22677088 TI - Dietary supplementation of an ellagic acid-enriched pomegranate extract attenuates chronic colonic inflammation in rats. AB - Dietary polyphenols present in Punica granatum (pomegranate), such as ellagitannins and ellagic acid (EA) have shown to exert anti-inflammatory and antioxidant properties. This study was designed to evaluate the effects of a dietary EA-enriched pomegranate extract (PE) in a murine chronic model of Cronh's disease (CD). Colonic injury was induced by intracolonic instillation of trinitrobenzensulfonic acid (TNBS). Rats were fed with different diets during 30 days before TNBS instillation and 2 weeks before killing: (i) standard, (ii) PE 250 mg/kg/day, (iii) PE 500 mg/kg/day, (iv) EA 10 mg/kg/day and (v) EA 10 mg/kg/day enriched-PE 250 mg/kg/day. Inflammation response was assessed by histology and MPO activity and TNF-alpha production. Besides, colonic expressions of iNOS, COX-2, p38, JNK, pERK1/2 MAPKs, IKBalpha and nuclear p65 NF-kappaB were studied by western blotting. MPO activity and the TNF-alpha levels were significantly reduced in dietary fed rats when compared with TNBS group. Similarly, PE and an EA-enriched PE diets drastically decreased COX-2 and iNOS overexpression, reduced MAPKs phosporylation and prevented the nuclear NF-kappaB translocation. Dietary supplementation of EA contributes in the beneficial effect of PE in this experimental colitis model and may be a novel therapeutic strategy to manage inflammatory bowel disease (IBD). PMID- 22677090 TI - Effect of diinosine polyphosphates on intraocular pressure in normotensive rabbits. AB - The ability of diinosine polyphosphates, diinosine triphosphate (Ip(3)I), diinosine tetraphosphate (Ip(4)I) and diinosine pentaphosphate (Ip(5)I) to modify intraocular pressure in normotensive New Zealand white rabbits was tested. Ip(5)I produced increase in intraocular pressure, while Ip(3)I and Ip(4)I produced a decrease. Ip(4)I was the most effective reducing intraocular pressure inducing a maximal decrease of intraocular pressure to 74.2 +/- 2.5% compared with the control value. Dose-response analysis demonstrated a concentration dependent pattern which presented a pD(2) value of 6.19 +/- 0.18, equivalent to an EC(50) of 0.63 MUM. Regarding the underlying mechanism used by Ip(4)I to reduce intraocular pressure, studies with agonists and antagonists revealed that Ip(4)I reduces intraocular pressure via P2Y receptors in the eye. We suggest that topical application of Ip(4)I to the cornea has therapeutic potential for lowering intraocular pressure, a major risk factor for glaucoma. PMID- 22677091 TI - Characterization of the spotted seal Phoca largha transcriptome using Illumina paired-end sequencing and development of SSR markers. AB - Next-generation sequencing provides a powerful new approach for developing functional genomic tools for non-model species. This study aims to investigate the spotted seal (Phoca largha) transcriptome by the approach of Illumina paired end sequencing technology. We obtained a total of 52,146,394 reads for the mixed tissues of liver and spleen from spotted seal. The de novo assemblies yielded 354,014 contigs and 178,466 unigenes. In addition, bioinformatics analysis revealed a total of 4425 simple sequence repeats (SSRs). Fifty SSRs were randomly selected to validate amplification and determine the degree of polymorphism in the genomic DNA pools. Thirty-five primer pairs successfully amplified expected DNA fragments and detected significant polymorphism among 28 spotted seal individuals. These results contribute to the understanding of the genetic makeup of spotted seal transcriptome and provide useful information for functional genomic research in this species. PMID- 22677093 TI - A two-stage mining framework to explore key risk conditions on one-vehicle crash severity. AB - This paper proposes a two-stage mining framework to explore the key risk conditions that may have contributed to the one-vehicle crash severity in Taiwan's freeways. In the first stage, a genetic mining rule (GMR) model is developed, using a novel stepwise rule-mining algorithm, to identify the potential risk conditions that best elucidate the one-vehicle crash severity. In the second stage, a mixed logit model is estimated, using the antecedent part of the mined-rules as explanatory variables, to test the significance of the risk conditions. A total of 5563 one-vehicle crash cases (226 fatalities, 1593 injuries and 3744 property losses) occurred in Taiwan's freeways over 2003-2007 are analyzed. The GMR model has mined 29 rules for use. By incorporating these 29 mined-rules into a mixed logit model, we further identify one key safe condition and four key risk conditions leading to serious crashes (i.e., fatalities and injuries). Each key risk condition is discussed and compared with its adjacent rules. Based on the findings, some countermeasures to rectify the freeway's serious one-vehicle crashes are proposed. PMID- 22677092 TI - Cost-effectiveness of nurse-led self-help for recurrent depression in the primary care setting: design of a pragmatic randomised controlled trial. AB - BACKGROUND: Major Depressive Disorder is a leading cause of disability, tends to run a recurrent course and is associated with substantial economic costs due to increased healthcare utilization and productivity losses. Interventions aimed at the prevention of recurrences may reduce patients' suffering and costs. Besides antidepressants, several psychological treatments such as preventive cognitive therapy (PCT) are effective in the prevention of recurrences of depression. Yet, many patients find long-term use of antidepressants unattractive, do not want to engage in therapy sessions and in the primary care setting psychologists are often not available. Therefore, it is important to study whether PCT can be used in a nurse-led self-help format in primary care. This study sets out to test the hypothesis that usual care plus nurse-led self-help for recurrent depression in primary care is feasible, acceptable and cost-effective compared to usual care only. DESIGN: Patients are randomly assigned to 'nurse-led self-help treatment plus usual care' (134 participants) or 'usual care' (134 participants). Randomisation is stratified according to the number of previous episodes (2 or 3 previous episodes versus 4 or more). The primary clinical outcome is the cumulative recurrence rate of depression meeting DSM-IV criteria as assessed by the Structured-Clinical-Interview-for-DSM-IV- disorders at one year after completion of the intervention. Secondary clinical outcomes are quality of life, severity of depressive symptoms, co-morbid psychopathology and self-efficacy. As putative effect-moderators, demographic characteristics, number of previous episodes, type of treatment during previous episodes, age of onset, self-efficacy and symptoms of pain and fatigue are assessed. Cumulative recurrence rate ratios are obtained under a Poisson regression model. Number-needed-to-be-treated is calculated as the inverse of the risk-difference. The economic evaluation is conducted from a societal perspective, both as a cost-effectiveness analysis (costs per depression free survival year) and as a cost-utility analysis (costs per quality adjusted life-year). DISCUSSION: The purpose of this paper is to outline the rationale and design of a nurse-led, cognitive therapy based self help aimed at preventing recurrence of depression in a primary care setting. Only few studies have focused on psychological self-help interventions aimed at the prevention of recurrences in primary care patients. TRIAL REGISTRATION: NTR3001 (http://www.trialregister.nl). PMID- 22677094 TI - Pivot and pass...Moving triage out of the way. PMID- 22677096 TI - Accurate patient identification in the emergency department: meeting the safety challenges. PMID- 22677097 TI - Comment on "Under-triage as a significant factor affecting transfer time between the emergency department and the intensive care unit". PMID- 22677098 TI - Effect of selected exercises on in-shoe plantar pressures in people with diabetes and peripheral neuropathy. AB - BACKGROUND: In people with diabetes and peripheral neuropathy (DM+PN), injury risk is not clearly known for weight bearing (WB) vs. non-weight bearing (NWB) exercise. In-shoe peak plantar pressures (PPP) often are used as a surrogate indicator of injury to the insensitive foot. OBJECTIVE: Compare PPPs in people with DM+PN during selected WB and NWB exercises. METHODS: Fifteen subjects with DM+PN participated. PPPs were recorded for the forefoot, midfoot, and heel during level walking and compared to; WB exercises--treadmill walking, heel and toe raises, sit to stands, stair climbing, single leg standing; and NWB exercises- stationary bicycling, balance ball exercise and plantar flexion exercise. RESULTS: Compared to level walking; mean forefoot PPP during treadmill walking was 13% higher, but this difference was eliminated when walking speed was used as a covariate. Mean PPPs were similar or substantially lower for other exercises, except for higher forefoot PPP with heel raise exercises. CONCLUSIONS: Slow progression and regular monitoring of insensitive feet are recommended for all exercises, but especially for heel raises, and increases in walking speed. The remaining WB and NWB exercises pose no greater risk to the insensitive foot due to increases in PPP compared to level walking. PMID- 22677099 TI - Micriamoeba tesseris nov. gen. nov. sp.: a new taxon of free-living small-sized Amoebae non-permissive to virulent Legionellae. AB - Investigation of soil amoebae in 11 cooling towers allowed us to isolate a major unknown small-sized amoeba population (SZA). However, SZA did not appear to be specific to cooling tower ecosystems since they are also a major amoeba population found in muds isolated from different points of a water treatment plant. The SSU-rDNA sequences from SZA strains did not match any known database sequences, suggesting that SZA constitutes a new amoeba taxon. We isolated and further described one of the SZA that we named Micriamoeba tesseris. The phylogenetic analyses showed that Micriamoeba tesseris belongs to the Amebozoa and branched together with genus Echinamoeba+Vermamoeba vermiformis. Phylogenetic analyses within the Micriamoeba group distinguished different subgroups of Micriamoeba strains according to their origin, i.e. cooling tower or mud. Although Micriamoeba are able to feed on viable E. coli cells, they do not uptake virulent Legionella pneumophila strains, thus enabling them to avoid infection by Legionella. Consequently, Micriamoeba is not directly involved in L. pneumophila multiplication. However, an indirect role of Micriamoeba in Legionella risk is discussed. PMID- 22677100 TI - Expression of the neocortical marker, RORbeta, in the entopallium and field L2 of adult chicken. AB - Two opposing hypotheses on the homology of the avian brain suggest that the dorsal ventricular ridge of birds is comparable in certain respects either to the neocortex or to the claustroamygdalar complex of mammals. To help resolve this issue, we examined in adult chicken brains the gene expression of RORbeta mRNA, a selective marker for layer IV of mammalian neocortex. RORbeta mRNA was expressed in neurons of the chicken's visual entopallium and auditory field L2, but not in other regions of the nidopallium, hyperpallium, mesopallium or arcopallium. Together with hodological evidence of direct thalamic projections conveying primary sensory information to the entopallium and field L2, our results support the contention that these two regions are composed of neurons comparable to those in layer IV of mammalian neocortex. PMID- 22677101 TI - Heterozygosity for the proteasomal Psmc1 ATPase is insufficient to cause neuropathology in mouse brain, but causes cell cycle defects in mouse embryonic fibroblasts. AB - The ubiquitin proteasome system (UPS) is a fundamental cellular pathway, degrading most unwanted intracellular soluble proteins. Dysfunction of the UPS has been associated with normal aging as well as various age-related pathological conditions, including chronic human neurodegenerative diseases such as Alzheimer's and Parkinson's diseases, leading to a significant interest in the involvement of this degradative system in neurones. We previously reported that the 26S proteasome was essential for neuronal homeostasis and survival in mouse brains following conditional genetic homozygous knockout of a key subunit of the multi-meric 26S proteasome (19S ATPase Psmc1). Here, we investigated the effects of Psmc1 heterozygosity in the mouse brain and primary mouse embryonic fibroblasts. Neuropathologically and biochemically, Psmc1 heterozygous (Psmc1(+/ )) knockout mice were indistinguishable from wild-type mice. However, we report a novel age-related accumulation of intraneuronal lysine 48-specific polyubiquitin positive granular staining in both wild-type and heterozygous Psmc1 knockout mouse brain. In Psmc1(+/-) MEFs, we found a significant decrease in PSMC1 levels, altered 26S proteasome assembly and a notable G2/M cell cycle arrest that was not associated with an increase in the cell cycle regulatory protein p21. The disturbance in cell cycle progression may be responsible for the growth inhibitory effects in Psmc1(+/-) MEFs. PMID- 22677102 TI - [Acute hepatitis: Don't forget the hepatitis caused by primary Epstein-Barr virus infection]. PMID- 22677103 TI - Characterization of Streptomyces plasmid-phage pFP4 and its evolutionary implications. AB - Autonomous-replicating plasmid pFP4 of Streptomyces sp. FR1 isolated from a heavy metal-contaminated land was cloned and sequenced. Surprisingly, the 40,949-bp pFP4 contains a cluster of 20 genes, resembling these chromosome-integrated prophages of Streptomyces sp. SPB78 and Streptomyces scabiei 87.22. Plasmid pFP4 could transfer by conjugation and a replication locus, iteron/repA/repB, was identified. The filtered FR1 culture could infect both FR1 and FR1 cured of pFP4 to form plaques, and also six out of 13 strains from the same land, but failed to form plaques on other seven strains from same source and all ten Streptomyces species from different sources. pFP4 phage particles were observed by transmission electron microscopy. Major structural proteins (capsid, portal and tail, etc.) of pFP4 virions were encoded by twelve pFP4 genes. pFP4 phage DNA contained 3' protruding cohesive ends of 9-nt. Streptomyces pFP4 represents a novel plasmid-phage. PMID- 22677104 TI - A model for the 3D chromatin architecture of pro and eukaryotes. AB - How do chromosomes fold and how does this depend on the organism and type of cell? This question has been addressed by a model and a methodology that uses only very basic constituents to capture the relevant features of folding. Key is the dynamic formation of loops within the chromosome. With this and entropy we show that the model is capable to describe the folding of human chromosomes in inter- and metaphase as well as for the Escherichia coli circular chromosomes. PMID- 22677105 TI - Socio-demographic factors associated with treatment against soil-transmitted helminth infections in children aged 12-59 months using the health facility approach alone or combined with a community-directed approach in a rural area of Zambia. AB - A health facility-based (HF) approach to delivering anthelminthic drugs to children aged 12-59 months in Zambia was compared with an approach where community-directed treatment (ComDT) was added to the HF approach (HF+ComDT). This paper reports on the socio-demographic factors associated with treatment coverage in the HF+ComDT and HF areas after 18 months of implementation. Data were collected by interviewing 288 and 378 caretakers of children aged 12-59 months in the HF+ComDT and HF areas, respectively. Bivariate and multivariate logistic regression analyses were used for data analysis. Statistically significant predictors of a child being treated were: a child coming from the HF+ComDT area, being 12-36 months old, the family having lived in the area for >20 years, coming from a household with only one under-five child and living <=3 km from the health facility. It is concluded that socio-demographic factors are of public health relevance and affect treatment coverage in both the HF+ComDT and the HF approaches. The implementation and strengthening of interventions like ComDT that bring treatment closer to households will enable more children to have access to treatment. PMID- 22677106 TI - Development of a fluorescence immunochromatographic assay for the detection of zeta globin in the blood of (--(SEA)) alpha-thalassemia carriers. AB - Southeast Asian deletion (--(SEA)) alpha-thalassemia is an inherited monogenic disorder of human hemoglobin, and embryonic globin zeta (hemoglobin zeta, zeta globin chain or Hb zeta chain) has been shown to be a marker that can be used for the identification of carriers of the (--(SEA)) alpha-thalassemia deletion. In this work, a fluorescence immunochromatographic assay (FL-ICA) was established to detect the zeta globin chain in the hemolysates of carriers of the (--(SEA)) alpha-thalassemia deletion. This assay can be completed within 10min using a simple UV detector and does not suffer from interference from the red background color of the hemolysate. A total of 314 blood samples were tested by FL-ICA and ELISA. The results of these assays were confirmed by PCR, the standard technique for genetic disease testing. The sensitivity and specificity of this novel FL-ICA were 100% and 98.0%, respectively; the corresponding values for the ELISA performed simultaneously were 100% and 99.2%, respectively. In conclusion, a new FL-ICA-a simple, fast, convenient, low-cost method-was developed that may be useful in both high-throughput screening and individual detection of the (- (SEA)) alpha-thalassemia deletion in carriers. Additionally, this qualitative FL ICA may enlighten the development of a new systems for analysis of other target molecules using whole-blood samples. PMID- 22677107 TI - A novel 506kb deletion causing epsilongammadeltabeta thalassemia. AB - We describe a novel deletion causing epsilongammadeltabeta thalassemia in a Pakistani family. The Pakistani deletion is 506kb in length, and the second largest epsilongammadeltabeta thalassemia deletion reported to date. It removes the entire beta globin gene (HBB) cluster, extending from 431kb upstream to 75kb downstream of the epsilon globin gene (HBE). The breakpoint junction occurred within a 160bp palindrome embedded in LINE/LTR repeats, and contained a short (9bp) region of direct homology which may have contributed to the recombination event. Characterization of the deletion breakpoints has been particularly challenging due to the complexity of DNA deletion, insertion and inversion, involving a multitude of methodologies, mirroring the changing DNA analysis technologies. PMID- 22677108 TI - [Dynamic of respiratory pathology in a service of pneumology in black Africa in the context of HIV infection from 1998 to 2007]. AB - INTRODUCTION: The pneumology in developing countries is practiced in a singular context: population mostly younger, endemic tuberculosis, high prevalence of HIV infection and growing pollution. OBJECTIVE: The aim of this study is to present respiratory pathology evolution in hospitalization of pneumology department in black Africa. METHODOLOGY: Our study is retrospective and descriptive. We consulted the register of hospitalization activities from January 1998 to December 2007. RESULTS: The age group of 20-49 years represents 78.36% of all patients. Tuberculosis (TB) remains the first affection from 1998 to 2007 with a frequency varying between 38.2% and 45.2%. The cases of pneumonia are in regression since 2001, but cases of febrile alveolar interstitial pneumonia (FAIP) increase. The pathologies bound to tobacco addiction are rare. HIV infection is associated to TB (82.86%), to pneumonia (77.22%), to FAIP (92.23%). On 832 cases of death recorded, 46.15% of deaths are assigned to TB, 15.98% to pneumonia and 14.66% to FAIP. The global lethality of the TB and the pneumonia is respectively 20.1% and 17.6%. The one of FAIP is 32.5%. Mortality attributable to TB and pneumonia decreases progressively but the one attributable to FAIP remains important. CONCLUSION: Respiratory pathology is dominated by TB, pneumonia and FAIP. These pathologies associated to HIV infection cause a strong mortality. PMID- 22677109 TI - [Unilateral bronchospasm during general anesthesia]. AB - We report a case of unilateral bronchospasm encountered following an induction of anesthesia of healthy young man with no significant past medical or surgical history. The differential diagnosis and management are discussed. Unilateral bronchospasm was probably caused by topical lidocaine injected with a Laryngojet injector at the vocal cords. PMID- 22677110 TI - [Spontaneous pneumothorax and Recklinghausen's disease: a case report]. AB - The Von Recklinghausen disease is a genetic hereditary neurofibromatosis. It causes neurofibroma, axillary and inguinal lentigines, and cafe-au-lait spots in the skin. It may affect the lung in 5 to 20% of cases, causing neurofibroma, infiltrative and cystic lesions, emphysematous or bubble injury leading to a chronic respiratory failure. The risk of pneumothorax in theses cases seems higher. Few reviews reported the pulmonary manifestations in the Recklinghausen disease and specially the pneumothorax as a complication while the direct relation between this neurofibromatosis and the lung disease is not clearly established yet. We report a case report of spontaneous pneumothorax with slow evolution complicating the course of a patient with Recklinghausen disease. PMID- 22677111 TI - Mark Twain: how to fathom the depth of your pet proteome. AB - The present review highlights recent progresses in the technique of combinatorial peptide ligand libraries (CPPL), a methodology that has much to offer for the detection of low- to very-low abundance proteins (nanograms/mL scale and below) in any proteome. In particular, advances in exploration of the urinary, plasma and tissue proteomes are discussed and evaluated. It is shown that when treating biological fluids, such as plasma, with CPLLs, the detection sensitivity, which in the control only reaches 10 ng/mL, can be enhanced to as high as 10 pg/mL, with an increment of sensitivity of three orders of magnitude. The possibility of using CPLLs as a two-dimensional pre-fractionation of any proteome is also evaluated: on the charge axis, CPLL capture can be implemented at no less than three different pH values (4.0, 7.2 and 9.3), thus permitting a capture of proteinaceous analytes bearing a net positive or net negative charge, respectively. When capture is performed in the absence of salts or at high levels of salts (of the Hofmeister series), one can favor the capture of hydrophilic vs. hydrophobic proteins, respectively. This would thus be a genuine 2D protocol, working on orthogonal separation principles (charge vs. hydrophobicity). As the horizon of CPLLs is expanding and its use is exponentially growing, we expect major breakthroughs in, e.g., biomarker discovery, a field that has suffered a decade of failures. PMID- 22677113 TI - Proteome response of an extraintestinal pathogenic Escherichia coli strain with zoonotic potential to human and chicken sera. AB - A subset of extraintestinal pathogenic Escherichia coli is zoonotic and has developed strategies to adapt to different host-specific environments. However, the underlying mechanisms of these adaptive strategies have yet to be discerned. Here, the proteomic response of an avian pathogenic E. coli strain, which appears indistinguishable from neonatal meningitis E. coli, was compared following growth in human and avian sera to determine whether it uses the same mechanisms to overcome the antibacterial effects of sera from different host species. Proteins involved in biosynthesis of iron receptors were up-regulated under both sera, suggesting that serum, regardless of the host of origin, is an iron-limited environment. However, several proteins involved in synthesis of nucleic acids, sulfur-containing amino acids and fatty acids, were differentially expressed in response to the sera from different hosts. Mutational analysis showed that this APEC strain required nucleotide biosynthesis during incubation in human, but not avian serum, and deletion of genes involved in the biosynthesis of sulfur containing amino acids increased its resistance to human serum. Continued investigation of the proteome of 'zoonotic' ExPEC strains, grown under other 'dual' host conditions, will contribute to our understanding of ExPEC pathogenesis and host specificity and development of effective therapies and control strategies. PMID- 22677112 TI - Heat shock protein 27 mediates the effect of 1,3,5-trihydroxy-13,13-dimethyl-2H pyran [7,6-b] xanthone on mitochondrial apoptosis in hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is a global public health problem which causes approximately 500,000 deaths annually. Considering that the limited therapeutic options for HCC, novel therapeutic targets and drugs are urgently needed. In this study, we discovered that 1,3,5-trihydroxy-13,13-dimethyl-2H-pyran [7,6-b] xanthone (TDP), isolated from the traditional Chinese medicinal herb, Garcinia oblongifolia, effectively inhibited cell growth and induced the caspase-dependent mitochondrial apoptosis in HCC. A two-dimensional gel electrophoresis and mass spectrometry-based comparative proteomics were performed to find the molecular targets of TDP in HCC cells. Eighteen proteins were identified as differently expressed, with Hsp27 protein being one of the most significantly down-regulated proteins induced by TDP. In addition, the following gain- and loss-of-function studies indicated that Hsp27 mediates mitochondrial apoptosis induced by TDP. Furthermore, a nude mice model also demonstrated the suppressive effect of TDP on HCC. Our study suggests that TDP plays apoptosis-inducing roles by strongly suppressing the Hsp27 expression that is specifically associated with the mitochondrial death of the caspase-dependent pathway. In conclusion, TDP may be a potential anti-cancer drug candidate, especially to cancers with an abnormally high expression of Hsp27. PMID- 22677114 TI - Interdisciplinary: Cultural competency and culturally congruent education for millennials in health professions. AB - The increasingly diverse multicultural and multigenerational student population in the United States requires that educators at all levels develop cultural knowledge, awareness, and sensitivity to help diverse learners fulfill their potential and to avoid cultural misunderstandings that can become obstacles or barriers to learning. The purpose of this study was to design and implement eclectic, creative, evidence-based interdisciplinary educational activities, along with culturally congruent teaching strategies, within a semester-long university course that promoted positive and culturally competent learning outcomes for culturally diverse, largely millennial students. The interdisciplinary course would prepare health professional students with the requisite knowledge and skills, through transformative learning that produces change agents, to provide culturally congruent and quality team-based care to diverse populations. This was a qualitative and quantitative study, which measured students' level of cultural awareness, competence, and proficiency pre and post the educational intervention. Instruments used for data collection included the Inventory for Assessing The Process of Cultural Competence-Student Version (IAPCC-SV) by Campinha-Bacote, course evaluations, students' feedback, and portfolio reflections. The study was conducted at a private academic institution located in the Mid-Atlantic region and the sample population included inter-professional students (N=106) from various health professions including nursing, pharmacy, and allied health sciences. Results from the pre- and post test IAPCC-SV survey revealed that mean scores increased significantly from pre test (60.8) to post-test (70.6). Thus, students' levels of cultural competency (awareness, knowledge, skills, desire, encounter) improved post-educational intervention, indicating that the teaching methods used in the course might be applied on a larger scale across the university system to cater to the nation's increasingly multi-cultural population. PMID- 22677115 TI - Has primary sclerosing cholangitis associated with Crohn's disease a better outcome? PMID- 22677116 TI - Autoimmune polyglandular syndrome type 2, alopecia universalis and Crohn's disease. AB - Autoimmune polyglandular syndromes are defined as a spectrum of association between 2 or more organ specific endocrinopaties and non-endocrine autoimmune diseases. Autoimmune polyglandular syndromes type 2 is characterized by the coexistence of adrenal failure with autoimmune thyroid disease and diabetes mellitus type 1. Inflammatory bowel diseases are rarely associated with these autoimmune disorders. Here, we report about a case of 33 years old male with known history of Crohn's colitis diagnosed in childhood. In 2003 the patient experienced sudden loss of hair, eyebrows, eyelashes, beard and body hair - alopecia universalis was diagnosed. At the age of 28, the patient was hospitalized with severe dehydration and clinical signs of ketoacidosis. Increased blood glucose (40 mmol/L), ketonuria and metabolic acidosis indicated diabetes mellitus type 1. In 2005, he had severe relapse of Crohn's disease and was treated with systemic corticosteroid. Although patient responded well to the induction therapy, fatigue, hypotension, bradycardia called for further investigations: free thyroxine - 6.99 pmol/L, thyroid-stimulating hormone >75 U/ml, anti-thyroid peroxidase antibodies >1000 U/mL, so diagnosis of Haschimoto thyroiditis was confirmed. Persistent hypotension and fatigue, recurrent hypoglycemic crises indicated a possible presence of hypo-function of adrenal glands. After complete withdrawal of corticosteroid therapy, low cortisol levels (69.4 nmol/L) and positive tetracosactide stimulation test proved adrenal cortex failure. Regardless of the intensive treatment for diabetes, hypothyroidism, adrenal insufficiency and Crohn's disease, it was extremely difficult to achieve and maintain control of all four diseases. PMID- 22677117 TI - Risk of developing tuberculosis under anti-TNF treatment despite latent infection screening. AB - BACKGROUND: In patients treated with TNF-antagonists, incident cases of tuberculosis (TB) after a negative screening have been reported, leading to the suggestion that improved TB testing is necessary. AIM: The aim of the current study is to establish the incidence of TB and its characteristics in patients with inflammatory bowel disease (IBD) under TNF antagonists to design improved prevention strategies. METHODS: IBD patients from a single center treated with anti-TNF therapy between January 2000 and September 2011 were identified through a database that prospectively records clinical data, treatments and adverse events. RESULTS: During the study period 423 patients received anti-TNF therapy. Screening for latent TB infection (LTBI) previous to anti-TNF treatment was positive in 30 patients (6.96%). Seven patients (1.65%) developed TB while under anti-TNF treatment. Six patients (five under immunosuppressant treatment) had a negative LTBI screening. TST was positive in one patient not receiving immunosuppressants, and was treated with isoniazid before starting anti-TNF therapy. In 4 patients TB was diagnosed within the first 16 weeks after starting anti-TNF therapy. Three cases had pulmonary TB and 4 extrapulmonary disease. CONCLUSIONS: In the IBD population under study, incidence of TB infection associated with anti-TNF therapy is higher than that reported in controlled trials and occurs early after treatment initiation. False negative results of LTBI despite appropriate measures may occur, suggesting that more effective screening strategies are needed. PMID- 22677118 TI - Resource utilization during pediatric to adult transfer of care in IBD. AB - BACKGROUND: The transition from pediatric to adult care for inflammatory bowel disease (IBD) is poorly understood. AIMS: To characterize this transfer of care, health resource utilization was assessed. METHODS: Patients transferred between 1999 and 2008 were studied. Utilization of health resources one year before transfer and one year after transfer was compared. Resource units assessed included: i) emergency department (ED) visits; ii) hospitalizations; iii) clinic visits; iv) surgical procedures; and v) endoscopies. Secondary outcomes included: i) documentation of patient non-compliance; ii) reason(s) for ED visit; iii) diagnoses most responsible for hospital admission; iv) medications; v) indications for surgery; vi) endoscopic findings; vii) and disease activity. RESULTS: 95 subjects were identified (48 female), of whom 69 had Crohn's disease (CD) and 26 had ulcerative colitis (UC). The average age of diagnosis was 12.9 years. Over their adult care interval, subjects had fewer clinic visits (2.56 versus 3.05 (p = 0.01)) and more documented non-compliance (43% versus 29% (p = 0.01)). No differences in ED visits (0.15 versus 0.18 (p = 0.71)), hospitalizations (0.13 versus 0.13 (p = 0.23)), surgical intervention (0.03 versus 0.05 (p = 0.53)) or endoscopies (0.37 versus 0.25 (p = 0.11)) were observed. IBD was active 66.7% of endoscopies under pediatric care versus only 23.8% under adult care (p = 0.003). The average activity of CD was also higher during the last year of pediatric care. CONCLUSIONS: Understanding the transition process can help to develop strategies needed to support patients and their families. PMID- 22677119 TI - [Vertebral primary malignant germ cell tumor of thoracic spine: an exceptional observation]. AB - Vertebral primary malignant germ cell tumors are rarely located in thoracic spine. We report the case of a 44-year-old female, in which a symptomatology including dorsal rachidial pain, intercostal neuralgia, straight and transit disorder revealed a thoracic vertebral primary malignant germ cell tumor. The sole location of a vertebral primary malignant germ cell tumor in adult, exceptionally reported in the literature, prompted us to relate this observation. PMID- 22677120 TI - Pseudoxanthoma elasticum in the differential diagnosis of axillary calcifications on mammography. PMID- 22677121 TI - Facial ecthyma gangrenosum in 2 preterm neonates. PMID- 22677122 TI - Generalized eruptive histiocytosis in a patient with chronic myelomonocytic leukemia. PMID- 22677123 TI - Surgical principles for achieving a functional and cosmetically acceptable scar. AB - Dermatologic surgery can sometimes result in scars that are less than satisfactory. Such results, and hence the need for scar revision, can be avoided with careful planning and the use of appropriate surgical techniques. In this practical review, we describe several techniques that will improve functional and cosmetic outcomes. While Z-plasty and its variants are simple yet essential surgical procedures, they can represent a challenge for less experienced surgeons. By gaining a clear understanding of the principles of Z-plasty, the dermatologic surgeon will be able to employ this technique, either alone or with other surgical techniques, in a range of clinical situations. PMID- 22677124 TI - Neutrophilic dermatosis on postmastectomy lymphedema. PMID- 22677125 TI - Contrasting acute graft-versus-host disease effects of Tim-3/galectin-9 pathway blockade dependent upon the presence of donor regulatory T cells. AB - T-cell immunoglobulin mucin-3 (Tim-3) is expressed on pathogenic T cells, and its ligand galectin-9 (gal-9) is up-regulated in inflamed tissues. When Tim-3(+) T cells encounter high gal-9 levels, they are deleted. Tim-3 is up-regulated on activated T cells during GVHD. Inhibition of Tim-3/gal-9 binding by infusion of a Tim-3-Ig fusion protein or Tim-3(-/-) donor T cells increased T-cell proliferation and GVHD lethality. When the Tim-3/gal-9 pathway engagement was augmented using gal-9 transgenic recipients, GVHD lethality was slowed. Together, these data indicate a potential for modulating this pathway to reduce disease by increasing Tim-3 or gal-9 engagement. Paradoxically, when Tim-3/gal-9 was inhibited in the absence of donor T-regulatory cells (Tregs), GVHD was inhibited. GVHD reduction was associated with decreased colonic inflammatory cytokines as well as epithelial barrier destruction. CD25-depleted Tim-3(-/-) donor T cells underwent increased activation-induced cell death because of increased IFN-gamma production. To our knowledge, these studies are the first to show that although the absence of Tim-3/gal-9 pathway interactions augments systemic GVHD, concurrent donor Treg depletion paradoxically and surprisingly inhibits GVHD. Thus, although donor Tregs typically inhibit GVHD, under some conditions, such Tregs actually may contribute to GVHD by reducing activation-induced T-cell death. PMID- 22677126 TI - HIV-1 infection of human macrophages directly induces viperin which inhibits viral production. AB - Macrophages are key target cells for HIV-1. HIV-1(BaL) induced a subset of interferon-stimulated genes in monocyte-derived macrophages (MDMs), which differed from that in monocyte-derived dendritic cells and CD4 T cells, without inducing any interferons. Inhibition of type I interferon induction was mediated by HIV-1 inhibition of interferon-regulated factor (IRF3) nuclear translocation. In MDMs, viperin was the most up-regulated interferon-stimulated genes, and it significantly inhibited HIV-1 production. HIV-1 infection disrupted lipid rafts via viperin induction and redistributed viperin to CD81 compartments, the site of HIV-1 egress by budding in MDMs. Exogenous farnesol, which enhances membrane protein prenylation, reversed viperin-mediated inhibition of HIV-1 production. Mutagenesis analysis in transfected cell lines showed that the internal S adenosyl methionine domains of viperin were essential for its antiviral activity. Thus viperin may contribute to persistent noncytopathic HIV-1 infection of macrophages and possibly to biologic differences with HIV-1-infected T cells. PMID- 22677127 TI - Polymorphisms of protein tyrosine phosphatase CD148 influence FcgammaRIIA dependent platelet activation and the risk of heparin-induced thrombocytopenia. AB - Heparin-induced thrombocytopenia (HIT) is due primarily to IgG antibodies specific to platelet factor 4/heparin complexes (PF4/Hs) that activate platelets via FcgammaRIIA. CD148 is a protein tyrosine phosphatase that regulates Src kinases and collagen-induced platelet activation. Three polymorphisms affecting CD148 (Q276P, R326Q, and D872E) were studied in HIT patients and 2 control groups, with or without antibodies to PF4/Hs. Heterozygote status for CD148 276P or 326Q alleles was less frequent in HIT patients, suggesting a protective effect of these polymorphisms. Aggregation tests performed with collagen, HIT plasma, and monoclonal antibodies cross-linking FcgammaRIIA showed consistent hyporesponsiveness of platelets expressing the 276P/326Q alleles. In addition, platelets expressing the 276P/326Q alleles exhibited a greater sensitivity to the Src family kinases inhibitor dasatinib in response to collagen or ALB6 cross linking FcgammaRIIA receptors. Moreover, the activatory phosphorylation of Src family kinases was considerably delayed as well as the phosphorylation of Linker for activation of T cells and phospholipase Cgamma2, 2 major signaling proteins downstream from FcgammaRIIA. In conclusion, this study shows that CD148 polymorphisms affect platelet activation and probably exert a protective effect on the risk of HIT in patients with antibodies to PF4/Hs. PMID- 22677128 TI - MYH10 protein expression in platelets as a biomarker of RUNX1 and FLI1 alterations. AB - RUNX1 gene alterations are associated with acquired and inherited hematologic malignancies that include familial platelet disorder/acute myeloid leukemia, primary or secondary acute myeloid leukemia, and chronic myelomonocytic leukemia. Recently, we reported that RUNX1-mediated silencing of nonmuscle myosin heavy chain IIB (MYH10) was required for megakaryocyte ploidization and maturation. Here we demonstrate that runx1 deletion in mice induces the persistence of MYH10 in platelets, and a similar persistence was observed in platelets of patients with constitutional (familial platelet disorder/acute myeloid leukemia) or acquired (chronic myelomonocytic leukemia) RUNX1 mutations. MYH10 was also detected in platelets of patients with the Paris-Trousseau syndrome, a thrombocytopenia related to the deletion of the transcription factor FLI1 that forms a complex with RUNX1 to regulate megakaryopoiesis, whereas MYH10 persistence was not observed in other inherited forms of thrombocytopenia. We propose MYH10 detection as a new and simple tool to identify inherited platelet disorders and myeloid neoplasms with abnormalities in RUNX1 and its associated proteins. PMID- 22677129 TI - Ezh2 augments leukemogenicity by reinforcing differentiation blockage in acute myeloid leukemia. AB - EZH2, a catalytic component of the polycomb repressive complex 2, trimethylates histone H3 at lysine 27 (H3K27) to repress the transcription of target genes. Although EZH2 is overexpressed in various cancers, including some hematologic malignancies, the role of EZH2 in acute myeloid leukemia (AML) has yet to be examined in vivo. In the present study, we transformed granulocyte macrophage progenitors from Cre-ERT;Ezh2(flox/flox) mice with the MLL-AF9 leukemic fusion gene to analyze the function of Ezh2 in AML. Deletion of Ezh2 in transformed granulocyte macrophage progenitors compromised growth severely in vitro and attenuated the progression of AML significantly in vivo. Ezh2-deficient leukemic cells developed into a chronic myelomonocytic leukemia-like disease with a lower frequency of leukemia-initiating cells compared with the control. Chromatin immunoprecipitation followed by sequencing revealed a significant reduction in the levels of trimethylation at H3K27 in Ezh2-deficient leukemic cells, not only at Cdkn2a, a known major target of Ezh2, but also at a cohort of genes relevant to the developmental and differentiation processes. Overexpression of Egr1, one of the derepressed genes in Ezh2-deficient leukemic cells, promoted the differentiation of AML cells profoundly. Our findings suggest that Ezh2 inhibits differentiation programs in leukemic stem cells, thereby augmenting their leukemogenic activity. PMID- 22677131 TI - Percutaneous ASD closure in a large Australian series: short- and long-term outcomes. AB - AIM: To assess the clinical and echocardiographic outcomes in patients referred for device closure of atrial septal defects in a tertiary referral hospital in Australia. METHODS: A prospective follow-up study was performed on all patients who had device closure of a secundum atrial septal defect (ASD) from June 1999 to December 2007. Clinical and echocardiographic data at the time of implantation and follow-up is presented. RESULTS: 176 patients were referred for shunt closure of ASD. All patients had a significant shunt defined as a shunt with right heart dilatation and/or a shunt ratio of at least 1.5:1. The majority were female (67%) and the average age was 36.5 +/- 22.7 years; age range 3-84. The average hospital admission time was 2.5 +/- 1.7 days. The average follow-up occurred at 3.7 +/- 3.6 months for the first follow-up and 26.3 +/- 18.2 months (range 3 months-7.8 years) for the long-term follow-up. Baseline echocardiogram findings showed the majority had a normal left ventricular ejection fraction (99%); average LVEF=63.2 +/- 7.2% while the right ventricle was dilated in 61% of patients. Procedure information: The average procedure time was 94.8 +/- 36.4 min. Procedural imaging was performed using Transoesophageal echocardiography (TOE) in 107 cases (61%); Intracardiac Echocardiography (ICE) in 69 (39%). Device use was as follows: Amplatzer=156 cases, Helex=18, and Starflex=2. Postprocedure shunt assessment by transthoracic echocardiography showed successful closure (no shunt or trivial shunt) in 99% cases. Two patients were referred for inpatient surgery due to a significant residual shunt in one case and an unstable device in another. One patient who had an unstable device had their device repositioned successfully. Atrial arrhythmia was the most common complication occurring in the peri implantation period in 12 cases (6%) with four further cases at final up. The high prevalence of right ventricular dilatation in 65% patients at baseline had improved significantly at the first and long term follow-up to 2% (p=0.0001). CONCLUSION: Device closure of secundum atrial septal defects in this large Australian cohort demonstrates a high procedural success rate with a low incidence of complications in the short and long term. PMID- 22677130 TI - Preclinical activity of a novel CRM1 inhibitor in acute myeloid leukemia. AB - Chromosome maintenance protein 1 (CRM1) is a nuclear export receptor involved in the active transport of tumor suppressors (e.g., p53 and nucleophosmin) whose function is altered in cancer because of increased expression and overactive transport. Blocking CRM1-mediated nuclear export of such proteins is a novel therapeutic strategy to restore tumor suppressor function. Orally bioavailable selective inhibitors of nuclear export (SINE) that irreversibly bind to CRM1 and block the function of this protein have been recently developed. Here we investigated the antileukemic activity of KPT-SINE (KPT-185 and KPT-276) in vitro and in vivo in acute myeloid leukemia (AML). KPT-185 displayed potent antiproliferative properties at submicromolar concentrations (IC50 values; 100 500 nM), induced apoptosis (average 5-fold increase), cell-cycle arrest, and myeloid differentiation in AML cell lines and patient blasts. A strong down regulation of the oncogene FLT3 after KPT treatment in both FLT3-ITD and wild type cell lines was observed. Finally, using the FLT3-ITD-positive MV4-11 xenograft murine model, we show that treatment of mice with oral KPT-276 (analog of KPT-185 for in vivo studies) significantly prolongs survival of leukemic mice (P < .01). In summary, KPT-SINE are highly potent in vitro and in vivo in AML. The preclinical results reported here support clinical trials of KPT-SINE in AML. PMID- 22677132 TI - Disrupted intracellular redox balance of the diplomonad fish parasite Spironucleus vortens by 5-nitroimidazoles and garlic-derived compounds. AB - The 5-nitroimidazole, metronidazole, has traditionally been employed in veterinary medicine to treat a range of infections including the diplomonad fish parasite Spironucleus. This study aims to determine the mode of action of metronidazole on Spironucleus vortens, including the specific mechanism of activation of the pro-drug and subsequent cellular targets of the drug metabolites. Due to the ban on use of metronidazole in the treatment of production animals in Europe and USA, garlic-derived compounds were also investigated as natural alternatives to metronidazole chemotherapy. Scanning electron microscopy (SEM) provided an overview of gross cellular damage caused by metronidazole and garlic derivatives. Proteomic analyses by 2D gel electrophoresis identified the proteins involved in specific covalent adduct formation with nitroimidazoles. Furthermore, thioredoxin reductase (TrxR) activity and non-protein thiol concentration were assayed in extracts of S. vortens before and after treatment with nitroimidazoles and garlic-derivatives. Metronidazole and garlic-derived compounds caused severe damage of trophozoites indicated by membrane blebbing and lysed cell debris. Analysis of the S. vortens proteome identified several proteins capable of specific nitroimidazole binding, including; uridine phosphorylase, enolase, protein disulphide isomerase, aminoacyl-histidine dipeptidase and malic enzyme. Of the compounds tested, metronidazole and the garlic-derived compound ajoene were the most effective at inhibiting TrxR activity and depleting non-protein thiols. These data suggest TrxR-mediated activation of nitroimidazoles, leading to depletion of non-protein thiols. Redox imbalance due to antioxidant failure is implicated as the mode of action of nitroimidazoles and garlic-derived compounds, ultimately leading to cell death. Possible synergy between garlic derivatives and metronidazole should be further investigated in vitro in order to determine their theoretical implications. PMID- 22677133 TI - Efficacy of a spot on combination containing imidacloprid 10% and moxidectin 1% (Advocate((r))/Advantage((r)) Multi, Bayer Animal Health) against Ancylostoma ceylanicum in cats. AB - Ancylostoma ceylanicum is a common zoonotic hookworm of dogs and cats, especially in the Asia-Pacific region. The objective of this study was to determine the efficacy of a spot on combination product containing imidacloprid 10% and moxidectin 1% (Advocate((r))/Advantage((r)) Multi, Bayer Animal Health) against A. ceylanicum in experimentally infected cats. Sixteen kittens were each subcutaneously injected with 100 infective third-stage larvae of A. ceylanicum. Kittens were stratified by egg count and randomly allocated into control and treatment groups. The kittens in the treatment group were each treated with a spot on combination of 10% (w/v) imidacloprid and 1% (w/v) moxidectin, administered topically at recommended label dose rates. The kittens in the control group were not treated. Egg counts were performed daily until the end of the study period and compared for the treated and control groups. No eggs were detected in the treated group of kittens within 4 days of treatment and faecal samples from this group remained negative throughout the rest of the study, resulting in a treatment efficacy (egg reduction) of 100% (P<0.0001). The egg counts remained high (993 +/- 666 epg) in the untreated control group for the rest of the study period. This study demonstrated that based on faecal egg count reduction, the spot on combination containing imidacloprid 10% (w/v) and moxidectin 1% (w/v) (Advocate((r))/Advantage((r)) Multi, Bayer Animal Health) given at the recommended dose is highly effective against infection with A. ceylanicum in cats. PMID- 22677134 TI - Genetic characterization of Toxoplasma gondii isolates from pigs intended for human consumption in Brazil. AB - This study genetically Toxoplasma gondii isolates obtained from pigs intended for human consumption in northeastern Brazil; multilocus PCR-RFLP and sequencing techniques were utilized. Bioassays were conducted using the brain and tongue of 20 pig heads purchased at butcher shops in the city of Ilheus, Bahia, Brazil. Overall, 11 T. gondii isolates designated TgPgBr06-16 were identified. Application of multilocus PCR-RFLP with seven molecular markers (SAG1, SAG2, SAG3, BTUB, C22-8, PK1 and Apico) identified six different genotypes. Isolates TgPgBr 06, 08, 11, 12, 14 and 15 were indistinguishable by this technique, forming a single genotype; the remaining isolates were characterized as distinct genotypes. However, when five genetic markers (SAG1, SAG2, SAG3, BTUB and c22-8) were employed in multilocus PCR-sequencing, all eleven strains of T. gondii were shown to be different. All isolates differed from Type I, II and III clonal genotypes using both genotyping techniques. These results demonstrate that the multilocus PCR-RFLP assay underestimated the true diversity of the T. gondii population in this study. Thus, DNA sequencing is the preferred technique to infer the genetic diversity and population structure of T. gondii strains from Brazil. Moreover, it is necessary to develop new molecular markers to group and characterize atypical T. gondii isolates from South America. PMID- 22677135 TI - The hare (Lepus granatensis) as potential sylvatic reservoir of Leishmania infantum in Spain. AB - Xenodiagnosis of Leishmania infection in hares (Lepus granatensis) from a focus of human leishmaniasis in Fuenlabrada at southwestern Madrid region (Spain) proved that they are infective to Phlebotomus perniciosus. Molecular characterization of isolates obtained from sand flies infected after xenodiagnosis demonstrates that hares were infected by Leishmania infantum. This is the first evidence of the transmission of L. infantum from hares to sand flies. Moreover the results confirm the role that these animals can play as wild reservoirs of leishmaniasis for the recent outbreak of visceral leishmaniasis in Madrid. PMID- 22677136 TI - Whole-heart dynamic three-dimensional magnetic resonance perfusion imaging for the detection of coronary artery disease defined by fractional flow reserve: determination of volumetric myocardial ischaemic burden and coronary lesion location. AB - AIMS: Dynamic three-dimensional-cardiac magnetic resonance (3D-CMR) perfusion proved highly diagnostic for the detection of angiographically defined coronary artery disease (CAD) and has been used to assess the efficacy of coronary stenting procedures. The present study aimed to relate significant coronary lesions as assessed by fractional flow reserve (FFR) to the volume of myocardial hypoenhancement on 3D-CMR adenosine stress perfusion imaging and to define the inter-study reproducibility of stress inducible 3D-CMR hypoperfusion. METHODS AND RESULTS: A total of 120 patients with known or suspected CAD were examined in two CMR centres using 1.5 T systems. The protocol included cine imaging, 3D-CMR perfusion during adenosine infusion, and at rest followed by delayed enhancement (DE) imaging. Fractional flow reserve was recorded in epicardial coronary arteries and side branches with >=2 mm luminal diameter and >40% severity stenosis (pathologic FFR < 0.75). Twenty-five patients underwent an identical repeat CMR examination for the determination of inter-study reproducibility of 3D CMR perfusion deficits induced by adenosine. Three-dimensional CMR perfusion scans were visually classified as pathologic if one or more segments showed an inducible perfusion deficit in the absence of DE. Myocardial ischaemic burden (MIB) was measured by segmentation of the area of inducible hypoenhancement and normalized to left ventricular myocardial volume (MIB, %). Three-dimensional CMR perfusion resulted in a sensitivity, specificity, and diagnostic accuracy of 90, 82, and 87%, respectively. Substantial concordance was found for inter-study reproducibility [Lin's correlation coefficient: 0.98 (95% confidence interval: 0.96-0.99)]. CONCLUSION: Three-dimensional CMR stress perfusion provided high diagnostic accuracy for the detection of functionally significant CAD. Myocardial ischaemic burden measurements were highly reproducible and allowed the assessment of CAD severity. PMID- 22677137 TI - Threshold crossing of device-based intrathoracic impedance trends identifies relatively increased mortality risk. AB - AIMS: Threshold crossings of impedance trends detected by implanted devices have been associated with clinically relevant heart failure events, but long-term prognosis of such events has not been demonstrated. The aim of this study is to examine the relationship between alterations in intrathoracic impedance and mortality risk in patients with implantable devices. METHODS AND RESULTS: We reviewed remote monitoring data in the de-identified Medtronic CareLink((r)) Discovery Link that captured intrathoracic impedance trends for >6 months. The initial 6 months of the cardiac and impedance trends were used as the observation period to create the patient groups and cross-referenced with the Social Security Death Index for mortality data. In our study cohort of 21 217 patients, 36% experienced impedance threshold crossing within the initial 6 months of monitoring (defined as the 'early threshold crossing' group). Patients with early threshold crossings demonstrated an increased risk of age- and gender-adjusted all-cause mortality [hazard ratio (HR) 2.15, 95% confidence interval (CI) 1.95 2.38, P< 0.0001]. Increased mortality risk remained significant when analysed in subgroups of patients without defibrillator shock (HR 2.10, 95% CI 1.90-2.34, P< 0.0001, n= 1621) or within those patients without device-detectable atrial fibrillation (AF) during the initial 6 months of monitoring (HR 2.09, 95% CI 1.86 2.34, P< 0.0001, n= 17 235). Both the number and the duration of early threshold crossings of impedance trends detectable by implanted devices were associated with increased mortality risk. Furthermore, the improvement of altered impedance trends portends more favourable prognosis. CONCLUSIONS: Threshold crossing of impedance trends detectable by implanted devices is associated with relatively increased mortality risk even after adjusted for demographic, device-detected AF, or defibrillator shocks. PMID- 22677138 TI - Cardiac catheter ablation under real-time magnetic resonance guidance. PMID- 22677139 TI - Clinical decision-making in a patient with mitral stenosis. PMID- 22677140 TI - Development of strength in dental silver amalgam. AB - OBJECTIVES: To characterize the development of strength during the setting process of dental silver amalgam in the context of 'early strength' measurements for standards compliance testing in relation to patient instructions, and demonstrate the applicability of the Hertzian 'ball on disc' method. MATERIALS AND METHODS: Sixteen dental silver amalgam products were tested using the 'ball on disc' protocol at 1, 2, 3, 4 and 24h after setting at 37 degrees C in air. The mixed materials were packed into a tapered steel disc mold (10mm diameter, 3mm thick) resting on a glass surface, slightly overfilled and carved level with a sharp edge, then ejected at ~10min and placed immediately into an incubator at 37 degrees C. Testing was in Hertzian mode, using a 20mm steel ball, with the specimen resting on a disc of glass-filled polyamide (E=10GPa) at a cross-head speed of 0.2mm/min on a universal testing machine (E3000, Instron). The load at first crack was recorded, as was the number of radial cracks produced. RESULTS: Radial cracking into 2-5 pieces, in a clinically-relevant (non-explosive) mode was observed in all cases. Considerable variation in setting rate between products, as indicated by the development of load at failure with time, was found. The distribution of normalized failure load values overall was lognormal (Weibull was excluded). The RMS coefficient of variation overall was 12.4%. SIGNIFICANCE: The ball-on-disc test provides a facile, relevant measure of the strength of dental silver amalgam, and is viable as a standards compliance test. Early strength testing at a minimum of 2h is suggested. PMID- 22677141 TI - Conformational dynamics of CYP3A4 demonstrate the important role of Arg212 coupled with the opening of ingress, egress and solvent channels to dehydrogenation of 4-hydroxy-tamoxifen. AB - BACKGROUND: Structure-based methods for P450 substrates are commonly used during drug development to identify sites of metabolism. However, docking studies using available X-ray structures for the major drug-metabolizing P450, CYP3A4, do not always identify binding modes supportive of the production of high-energy toxic metabolites. Minor pathways such as P450-catalyzed dehydrogenation have been experimentally shown to produce reactive products capable of forming biomolecular adducts which can lead to increased risk toxicities. 4-Hydroxy-tamoxifen (4OHT) is metabolized by CYP3A4 via competing hydroxylation and dehydrogenation reactions. METHODS: Ab initio gas-phase electronic structural characterization of 4OHT was used to develop a docking scoring scheme. Conformational sampling of CYP3A4 with molecular dynamics simulations along multiple trajectories were used to generate representative structures for docking studies using recently published heme parameters. A key predicted binding mode was tested experimentally using site-directed mutagenesis of CYP3A4 and liquid chromatography-mass spectroscopy analysis. RESULTS: Docking with MD-refined CYP3A4 structures incorporating hexa-coordinate heme parameters identifies a unique binding mode involving ARG212 and channel 4, unobserved in the starting PDB ID: 1TQN X-ray structure. The models supporting dehydrogenation are consistent with results from in vitro incubations. GENERAL SIGNIFICANCE: Our models indicate that coupled structural contributions of the ingress, egress and solvent channels to the CYP3A4 active site geometries play key roles in the observed 4OHT binding modes. Thus adequate sampling of the conformational space of these drug-metabolizing promiscuous enzymes is important for substrates that may bind in malleable regions of the enzyme active-site. PMID- 22677143 TI - Minocycline cannot protect neurons against bilirubin-induced hyperexcitation in the ventral cochlear nucleus. AB - Excitotoxicity has been suggested to play an important role in many central nervous system diseases, particularly in bilirubin encephalopathy. Minocycline treatment has been proposed to be one of the most promising potential therapies for excitotoxicity-induced neurological disorders. However, some key questions, such as the electrophysiological effect of minocycline on neuronal excitability and hyperexcitation in pathological conditions, require clarification. In this study, using patch-clamp techniques, we showed that bilirubin increased the frequency of both spontaneous excitatory postsynaptic currents (sEPSCs) and neuronal firing in isolated ventral cochlear nucleus (VCN) neurons at postnatal days 11-14 (P11-14) in rats but it did not affect the amplitude of sEPSCs or glutamate-activated (I(Glu)) currents. However, minocycline had no effect on sEPSC frequency or I(Glu) amplitude. Furthermore, minocycline pretreatment did not abolish bilirubin-induced sEPSC potentiation or neuron firing. These data suggest that minocycline does not affect excitatory synaptic transmission or hyperexcitation induced by bilirubin in VCN neurons. From these results, we propose that the neuroprotective efficacy of minocycline, if it can protect neurons against neurotoxicity induced by substances like bilirubin, is mediated by either an alternative mechanism or downstream events post neuronal hyperexcitation. Certainly, additional investigation of the neuroprotective effects of minocycline is required before embarking on further clinical trials. PMID- 22677144 TI - The metabolic syndrome in patients undergoing knee and hip arthroplasty: trends and in-hospital outcomes in the United States. AB - We evaluated the impact of metabolic syndrome (MetS) on perioperative outcomes in patients undergoing total joint arthroplasty. Using the Nationwide Inpatient Sample, patients with MetS were identified if they had at least 3 of 4 component comorbidities (obesity, dyslipidemia, hypertension, and diabetes). Patient demographics, in-hospital outcomes, and cost were compared between patients with and patients without MetS. Trends were studied for 3-year periods between 2000 and 2008. The prevalence of MetS increased over time, reaching 14% (total knee arthroplasty) and 8.7% (total hip arthroplasty) most recently. Metabolic syndrome was overproportionately prevalent among female total knee arthroplasty recipients, male total hip arthroplasty recipients, and patients in the minority race group. In the regression analysis, MetS was an independent risk factor for the development of major complications, nonroutine discharge, and increased hospital cost. Given the increasing rates of MetS and its association with higher risk for major complications among total joint arthroplasty recipients, further research into the impact of this disease complex is warranted. PMID- 22677145 TI - The influence of preoperative deformity on valgus correction angle: an analysis of 503 total knee arthroplasties. AB - We prospectively studied variations in valgus correction angle (VCA) and the influence of preoperative limb deformity on VCA in 503 consecutive total knee arthroplasties done in 393 patients. The percentage of limbs that had VCA values less than 5 degrees was 10.9%, and that with VCA values greater than 7 degrees was 44.9%. The percentage of limbs with VCA greater than 7 degrees was significantly more in varus knees, and that with VCA less than 5 degrees was significantly more in valgus knees; preoperative deformity showed a significant correlation with VCA. Choosing a fixed-routine VCA of 5 degrees to 7 degrees may cause an unacceptable planning error that may be minimized by individualizing VCA or using computer navigation. PMID- 22677142 TI - Stress-induced sensitization of cortical adrenergic receptors following a history of cannabinoid exposure. AB - The cannabinoid receptor agonist, WIN 55,212-2, increases extracellular norepinephrine levels in the rat frontal cortex under basal conditions, likely via desensitization of inhibitory alpha2-adrenergic receptors located on norepinephrine terminals. Here, the effect of WIN 55,212-2 on stress-induced norepinephrine release was assessed in the medial prefrontal cortex (mPFC), in adult male Sprague-Dawley rats using in vivo microdialysis. Systemic administration of WIN 55,212-2 30 min prior to stressor exposure prevented stress induced cortical norepinephrine release induced by a single exposure to swim when compared to vehicle. To further probe cortical cannabinoid-adrenergic interactions, postsynaptic alpha2-adrenergic receptor (AR)-mediated responses were assessed in mPFC pyramidal neurons using electrophysiological analysis in an in vitro cortical slice preparation. We confirm prior studies showing that clonidine increases cortical pyramidal cell excitability and that this was unaffected by exposure to acute stress. WIN 55,212-2, via bath application, blocked postsynaptic alpha2-AR mediated responses in cortical neurons irrespective of exposure to stress. Interestingly, stress exposure prevented the desensitization of alpha2-AR mediated responses produced by a history of cannabinoid exposure. Together, these data indicate the stress-dependent nature of cannabinoid interactions via both pre- and postsynaptic ARs. In summary, microdialysis data indicate that cannabinoids restrain stress-induced cortical NE efflux. Electrophysiology data indicate that cannabinoids also restrain cortical cell excitability under basal conditions; however, stress interferes with these CB1-alpha2 AR interactions, potentially contributing to over-activation of pyramidal neurons in mPFC. Overall, cannabinoids are protective of the NE system and cortical excitability but stress can derail this protective effect, potentially contributing to stress-related psychopathology. These data add to the growing evidence of complex, stress-dependent modulation of monoaminergic systems by cannabinoids and support the potential use of cannabinoids in the treatment of stress-induced noradrenergic dysfunction. PMID- 22677146 TI - Minimum 6-year follow-up of revision total knee arthroplasty without patella reimplantation. AB - Management options for the polyethylene patellar button during a revision total knee arthroplasty (TKA) include retention, revision, or removal of the button without replacement (patelloplasty). Our purpose was to determine the midterm outcome of patients undergoing revision TKA with patelloplasty. We retrospectively reviewed a single surgeon's database for patients undergoing such surgery from May 2001 to June 2005 and identified 33 (34 knees). The 25 patients (26 knees) who had at least 6 years' follow-up formed our study group. We compared preoperative and final follow-up Knee Society Scores and radiographs. Mean Knee Society Scores had increased from 50 (range, 23-88) to 93 (range, 41 100), respectively. No patient required additional surgery. We conclude that, at midterm follow-up, patelloplasty appears to be a satisfactory option in the management of the patella in revision TKA. PMID- 22677147 TI - Community psychological stressor-induced secondary sex ratio decline after a seismic sequence in the Greek island of Zakynthos. AB - The secondary sex ratio (the ratio of boys to girls at birth) may demonstrate a decline following community stress-inducing major destructive events. This study aims to investigate whether or not moderate adverse life events, in conjunction with endogenous psychological characteristics, can induce sufficient community stress to affect the sex ratio. From April 3rd to May 8th 2006 a moderate sized earthquake sequence occurred offshore the Greek island of Zakynthos, which had been hit by a destructive earthquake half a century earlier. The monthly sex ratio after the earthquake sequence was estimated and compared with that of previous and following years. Eleven months after the onset of the earthquakes the sex ratio fell to 1.000, and during the next two months (March and April) it declined further to 0.612. The sex ratio one year before its decline was 1.158 and over a total 6-year period, 3 years before and 3 years after the sequence, it was 1.063; the March-April decline in male births is significant (OR=0.53, 95% CI=0.32-0.86, p=0.013, and OR=0.57, 95% CI=0.36-0.91, p=0.023, respectively). Also, the number of boys relative to girls in March-April 2007 was significantly lower than during the same months 3 years before and after the sequence (OR=0.50, 95% CI=0.31-0.82, p=0.007). The findings suggest that basic biological characteristics, such as the sex ratio, can be affected by psychological stressors interwoven with the pertaining psychology of the population. PMID- 22677149 TI - Classifying minimally disabled multiple sclerosis patients from resting state functional connectivity. AB - Multiple sclerosis (MS), a variable and diffuse disease affecting white and gray matter, is known to cause functional connectivity anomalies in patients. However, related studies published to-date are post hoc; our hypothesis was that such alterations could discriminate between patients and healthy controls in a predictive setting, laying the groundwork for imaging-based prognosis. Using functional magnetic resonance imaging resting state data of 22 minimally disabled MS patients and 14 controls, we developed a predictive model of connectivity alterations in MS: a whole-brain connectivity matrix was built for each subject from the slow oscillations (<0.11 Hz) of region-averaged time series, and a pattern recognition technique was used to learn a discriminant function indicating which particular functional connections are most affected by disease. Classification performance using strict cross-validation yielded a sensitivity of 82% (above chance at p<0.005) and specificity of 86% (p<0.01) to distinguish between MS patients and controls. The most discriminative connectivity changes were found in subcortical and temporal regions, and contralateral connections were more discriminative than ipsilateral connections. The pattern of decreased discriminative connections can be summarized post hoc in an index that correlates positively (rho=0.61) with white matter lesion load, possibly indicating functional reorganisation to cope with increasing lesion load. These results are consistent with a subtle but widespread impact of lesions in white matter and in gray matter structures serving as high-level integrative hubs. These findings suggest that predictive models of resting state fMRI can reveal specific anomalies due to MS with high sensitivity and specificity, potentially leading to new non-invasive markers. PMID- 22677148 TI - States of mind: emotions, body feelings, and thoughts share distributed neural networks. AB - Scientists have traditionally assumed that different kinds of mental states (e.g., fear, disgust, love, memory, planning, concentration, etc.) correspond to different psychological faculties that have domain-specific correlates in the brain. Yet, growing evidence points to the constructionist hypothesis that mental states emerge from the combination of domain-general psychological processes that map to large-scale distributed brain networks. In this paper, we report a novel study testing a constructionist model of the mind in which participants generated three kinds of mental states (emotions, body feelings, or thoughts) while we measured activity within large-scale distributed brain networks using fMRI. We examined the similarity and differences in the pattern of network activity across these three classes of mental states. Consistent with a constructionist hypothesis, a combination of large-scale distributed networks contributed to emotions, thoughts, and body feelings, although these mental states differed in the relative contribution of those networks. Implications for a constructionist functional architecture of diverse mental states are discussed. PMID- 22677150 TI - Ultra-high resolution diffusion tensor imaging of the microscopic pathways of the medial temporal lobe. AB - Diseases involving the medial temporal lobes (MTL) such as Alzheimer's disease and mesial temporal sclerosis pose an ongoing diagnostic challenge because of the difficulty in identifying conclusive imaging features, particularly in pre clinical states. Abnormal neuronal connectivity may be present in the circuitry of the MTL, but current techniques cannot reliably detect those abnormalities. Diffusion tensor imaging (DTI) has shown promise in defining putative abnormalities in connectivity, but DTI studies of the MTL performed to date have shown neither dramatic nor consistent differences across patient populations. Conventional DTI methodology provides an inadequate depiction of the complex microanatomy present in the medial temporal lobe because of a typically employed low isotropic resolution of 2.0-2.5 mm, a low signal-to-noise ratio (SNR), and echo-planar imaging (EPI) geometric distortions that are exacerbated by the inhomogeneous magnetic environment at the skull base. In this study, we pushed the resolving power of DTI to near-mm isotropic voxel size to achieve a detailed depiction of mesial temporal microstructure at 3 T. High image fidelity and SNR at this resolution are achieved through several mechanisms: (1) acquiring multiple repetitions of the minimum field of view required for hippocampal coverage to boost SNR; (2) utilizing a single-refocused diffusion preparation to enhance SNR further; (3) performing a phase correction to reduce Rician noise; (4) minimizing distortion and maintaining left-right distortion symmetry with axial-plane parallel imaging; and (5) retaining anatomical and quantitative accuracy through the use of motion correction coupled with a higher-order eddy current correction scheme. We combined this high-resolution methodology with a detailed segmentation of the MTL to identify tracks in all subjects that may represent the major pathways of the MTL, including the perforant pathway. Tractography performed on a subset of the data identified similar tracks, although they were lesser in number. This detailed analysis of MTL substructure may have applications to clinical populations. PMID- 22677151 TI - Colorectal cancer incidence in Germany: stage-shift 6 years after implementation of a colonoscopy screening program. AB - BACKGROUND: In 2002, colonoscopy was introduced as a tool for colorectal cancer screening in Germany. The long-term objective was to reduce the incidence in colorectal cancer (CRC) by detection and removal of advanced adenomas. Currently, the effect of colonoscopy screening on the population-based incidence of CRC in Germany is unknown. METHODS: We provide data on stage-specific (age-standardized) incidence rates in three federal states in Germany, 6 years after the implementation of colonoscopy. RESULTS: Between 2002 and 2008 a statistically significant decrease in CRC incidence could be observed (annually 3.0%, 95% confidence interval [CI]: -3.8; -2.2). The decline could be observed in all advanced tumor categories (T2, T3, and T4), whereas the incidence of in situ carcinomas (Tis) increased annually by 51.6% (95% CI: 28.0; 79.4) until 2004, and remained stable until 2008. CONCLUSION: The observed changes cannot be attributed definitively to the screening activities, but the presented data support a possible causal association. PMID- 22677153 TI - Beyond targeting malignant B cells. PMID- 22677152 TI - A population-based study of hedgehog pathway gene variants in relation to the dual risk of basal cell carcinoma plus another cancer. AB - INTRODUCTION: A personal history of basal cell carcinoma (BCC) is associated with increased risk of other malignancies, but the reason is unknown. The hedgehog pathway is critical to the etiology of BCC, and is also believed to contribute to susceptibility to other cancers. This study tested the hypothesis that hedgehog pathway and pathway-related gene variants contribute to the increased risk of subsequent cancers among those with a history of BCC. METHODS: The study was nested within the ongoing CLUE II cohort study, established in 1989 in Washington County, Maryland, USA. The study consisted of a cancer-free control group (n=2296) compared to three different groups of cancer cases ascertained through 2007, those diagnosed with: (1) Other (non-BCC) cancer only (n=2349); (2) BCC only (n=534); and (3) BCC plus other cancer (n=446). The frequencies of variant alleles were compared among these four groups for 20 single nucleotide polymorphisms (SNPs) in 6 hedgehog pathway genes (SHH, IHH, PTCH2, SMO, GLI1, SUFU), and also 22 SNPs in VDR and 8 SNPs in FAS, which have cross-talk with the hedgehog pathway. RESULTS: Comparing those with both BCC and other cancer versus those with no cancer, no significant associations were observed for any of the hedgehog pathway SNPs, or for the FAS SNPs. One VDR SNP was nominally significantly associated with the BCC cancer-prone phenotype, rs11574085 [per minor allele odds ratio (OR) 1.38, 95% confidence interval (CI) 1.05-1.82; p value=0.02]. CONCLUSION: The hedgehog pathway gene SNPs studied, along with the VDR and FAS SNPs studied, are not strongly associated with the BCC cancer-prone phenotype. PMID- 22677154 TI - Circulating tumour cells as biomarkers in early breast cancer. PMID- 22677155 TI - Lenalidomide in combination with rituximab for patients with relapsed or refractory mantle-cell lymphoma: a phase 1/2 clinical trial. AB - BACKGROUND: The combination of rituximab and lenalidomide has shown promise for the treatment of mantle-cell lymphoma (MCL) in preclinical studies. We aimed to identify the maximum tolerated dose (MTD) of lenalidomide when combined with rituximab in a phase 1 trial and to assess the efficacy and safety of this combination in a phase 2 trial in patients with relapsed or refractory MCL. METHODS: Patients with relapsed or refractory MCL who had received one to four previous lines of treatment were enrolled in this single-arm, open-label, phase 1/2 trial at MD Anderson Cancer Center. In phase 1, to identify the MTD of lenalidomide, four patient cohorts received escalating doses (10, 15, 20, and 25 mg) of daily oral lenalidomide on days 1-21 of each 28-day cycle. 375 mg/m(2) intravenous rituximab was also administered in four weekly doses during cycle 1 only. In phase 2, patients received rituximab plus the MTD of lenalidomide, following the same cycles as for phase 1. Treatment in both phases continued until disease progression, stem-cell transplantation, or severe toxicity. The primary efficacy endpoint was overall response (complete or partial response). The secondary efficacy endpoint was survival. We used the Kaplan-Meier method to estimate response duration, progression-free survival, and overall survival. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00294632. FINDINGS: 52 patients were enrolled between Feb 10, 2006 and July 30, 2009, 14 in phase 1 and 44 (including six patients who received the MTD of lenalidomide in the phase 1 portion) in phase 2. The MTD was 20 mg lenalidomide. One patient who was treated with 25 mg lenalidomide developed a grade 4 non-neutropenic infection and died. In the phase 2 portion of the study, grade 3-4 haematological toxicities included neutropenia (29 patients), lymphopenia (16 patients), leucopenia (13 patients), and thrombocytopenia (ten patients). There were only two episodes of febrile neutropenia. Among 44 patients in phase 2, 25 (57%) had an overall response: 16 (36%) had a complete response and nine (20%) had a partial response. The median response duration was 18.9 months (95% CI 17.0 months to not reached [NR]). The median progression-free survival was 11.1 months (95% CI 8.3 to 24.9 months), and the median overall survival was 24.3 months (19.8 months to NR). Five of 14 patients who had received bortezomib treatment before enrolment achieved an overall response. INTERPRETATION: Oral lenalidomide plus rituximab is well tolerated and effective for patients with relapsed or refractory MCL. FUNDING: Celgene. PMID- 22677156 TI - Circulating tumour cells in non-metastatic breast cancer: a prospective study. AB - BACKGROUND: The identification of circulating tumour cells correlate with poor prognosis in metastatic breast cancer, but there are few data describing the importance of circulating tumour cells in patients with non-metastatic disease. Our aim was to establish if circulating tumour cells predicted worse outcome in patients with non-metastatic breast cancer. METHODS: We prospectively collected data on circulating tumour cells at the time of definitive surgery from chemonaive patients with stage 1-3 breast cancer from February, 2005, to December, 2010. We deemed eligible all patients with operable breast cancer presenting at The University of Texas MD Anderson Cancer Center (Houston, TX, USA). Patients were ineligible if they had bilateral breast cancer or any other malignancy within 5 years of the diagnosis of the present cancer. We measured circulating tumour cells with the CellSearch System (Veridex, Raritan, NJ). We correlated findings of circulating tumour cells with standard tumour characteristics, including tumour size and grade; oestrogen and progesterone receptor and human epidural growth factor receptor 2 (HER2) status; and axillary lymph node status with chi(2) or Fisher exact tests. We assessed outcomes at a median follow-up of 35 months. Log-rank test and Cox regression analysis was applied to establish the association of circulating tumour cells with progression free and overall survival. FINDINGS: No patients reported adverse events or complications from blood collections. We identified one or more circulating tumour cells in 73 (24%) of 302 patients. Detection of one or more circulating tumour cells predicted both decreased progression-free survival (log-rank p=0.005; hazard ratio [HR] 4.62, 95% CI 1.79-11.9) and overall survival (log-rank p=0.01; HR 4.04, 1.28-12.8). INTERPRETATION: The presence of one or more circulating tumour cells predicted early recurrence and decreased overall survival in chemonaive patients with non-metastatic breast cancer. These results suggest that assessment of circulating tumour cells might provide important prognostic information in these patients. FUNDING: Society of Surgical Oncology, Morgan Welch Inflammatory Breast Cancer Program, The University of Texas MD Anderson Cancer Center, and the State of Texas Rare and Aggressive Breast Cancer Research Program. PMID- 22677157 TI - Feasibility and outcomes of transcatheter aortic valve implantation in high-risk patients with stenotic bicuspid aortic valves. AB - Little is known about transcatheter aortic valve implantation (TAVI) in patients with bicuspid aortic valve stenosis, which usually represents a contraindication. The aim of this study was to assess the feasibility and the results of TAVI in this patient subset. Of 316 high-risk patients with severe aortic stenosis who underwent TAVI from January 2009 to January 2012, 15 (5%) had documented bicuspid aortic valves. They were treated using a transarterial approach, using the Medtronic CoreValve system. Patients were aged 80 +/- 10 years, in New York Heart Association functional classes III and IV. The mean aortic valve area was 0.8 +/- 0.3 cm(2), and the mean gradient was 60 +/- 19 mm Hg. The mean calcium score, calculated using multislice computed tomography, was 4,553 +/- 1,872 arbitrary units. The procedure was successful in all but 1 patient. Major adverse events, according to Valvular Academic Research Consortium definitions, were encountered in 1 patient (death). The mean postimplantation prosthetic gradient was 11 +/- 4 mm Hg, and <=1+ periprosthetic leaks were observed in all but 2 patients. The mean prosthetic ellipticity index was 0.7 +/- 0.2 at the level of the native annulus and 0.8 +/- 0.2 at the level of the prosthetic leaflets. After a mean follow-up period of 8 +/- 7 months, 1 patient had died from aortic dissection; there were no additional adverse events. All but 2 hospital survivors were in New York Heart Association class I or II. In conclusion, the present series suggests that transarterial Medtronic CoreValve implantation is feasible in selected patients with bicuspid aortic valve and may lead to short-term hemodynamic and clinical improvement. PMID- 22677158 TI - Factors that influence Staphylococcus epidermidis growth in parenteral nutrition with and without lipid emulsion: a study framework to inform maximum duration of infusion policy decisions. AB - BACKGROUND & AIMS: Recommendations limit infusion of parenteral nutrition (PN) from bags with lipid to 24 h (48 h if lipid free) because lipid putatively encourages contaminant growth. This study aimed to examine these recommendations and identify factors affecting Staphylococcus epidermidis growth in PN. METHODS: S. epidermidis growth was assessed in quadruplicate in 12 PN regimens, with and without lipid and varying glucose concentrations. RESULTS: Baseline colony forming units (cfu)/mL (32.6) less than doubled at 48 h in all infusates. In PN infusates (pH 6.2 + 0.02 (SEM)) growth was independently increased by the presence of 5% w/v lipid (14.2 cfu/mL; P = 0.028), and glucose concentration (25.6 cfu/mL per 10% increase in w/v glucose; P = 0.003). In a separate analysis growth was stimulated by energy density (27.7 cfu/1000 kcal non-nitrogen energy in 2 L; P = 0.002), without a significant effect of % non-protein energy from lipid (-2.6 cfu/ml per 10%). CONCLUSIONS: Using a framework developed to examine growth of potential contaminants in PN, no evidence was found to support the specific recommendation to restrict the maximum infusion duration of lipid containing PN to a greater extent than lipid free PN. S. epidermidis growth was not only affected by the presence of lipid, but also glucose concentration and energy density. PMID- 22677159 TI - Lasting effects of a 2-year diabetes self-management support intervention: outcomes at 1-year follow-up. AB - INTRODUCTION: Diabetes-related health improvements achieved from self-management education interventions are not sustained long-term. We examined the health effects at 1 year follow-up of a 2-year, empowerment-based, diabetes self management support intervention designed for African Americans. METHODS: We collected data from 52 African American adults with type 2 diabetes who completed the 3-year study. The intervention consisted of weekly groups led by 2 health care professionals and emphasized experiential learning, emotional coping, problem solving, goal setting, and action planning; group discussion was guided by participant-identified self-management priorities and concerns. Measurements were taken at baseline, 24 months (postintervention), and 36 months (1 year follow-up) to assess glycemic control; weight; body mass index; serum cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels; systolic and diastolic blood pressure; self-care behaviors; diabetes-specific quality of life; and diabetes empowerment. RESULTS: Following the 2-year diabetes self-management support intervention, we found significant improvements for following a healthy diet (P = .03), spacing carbohydrates evenly across the day (P = .005), using insulin as recommended (P = .047), and achieving diabetes-specific quality of life (P = .02). At 1-year follow-up, not only did participants sustain the behavioral improvements made in the 2-year diabetes self management support intervention, but they also demonstrated additional improvements in glycemic control (P < .001) and in serum cholesterol (P < .001) and low-density lipoprotein cholesterol levels (P = .001). CONCLUSION: Participation in an empowerment-based diabetes self-management support intervention may have a positive and enduring effect on self-care behaviors and on metabolic and cardiovascular health. PMID- 22677162 TI - Physical functional outcome assessment of patients with major burns admitted to a UK Burn Intensive Care Unit. AB - Determining the discharge outcome of burn patients can be challenging and therefore a validated objective measure of functional independence would assist with this process. We developed the Functional Assessment for Burns (FAB) score to measure burn patients' functional independence. FAB scores were taken on discharge from ICU (FAB 1) and on discharge from inpatient burn care (FAB 2) in 56 patients meeting the American Burn Association criteria for major burn. We retrospectively analysed prospectively collected data to measure the progress of patients' physical functional outcomes and to evaluate the predictive validity of the FAB score for discharge outcome. Mean age was 38.6 years and median burn size 35%. Significant improvements were made in the physical functional outcomes between FAB 1 and FAB 2 scores (p<0.0001). 48 patients were discharged home, 8 of these with social care. 8 patients were transferred to another hospital for further inpatient rehabilitation. FAB 1 score (<= 9) is strongly associated with discharge outcome (p<0.006) and as such can be used to facilitate early discharge planning. FAB 2 score (<= 26) independently predicts discharge outcome (p<0.0001) and therefore is a valid outcome measure to determine discharge outcome of burn patients. PMID- 22677161 TI - School readiness among children insured by Medicaid, South Carolina. AB - INTRODUCTION: The American Academy of Pediatrics recommends a schedule of age specific well-child visits through age 21 years. For children insured by Medicaid, these visits are called Early and Periodic Screening, Diagnosis, and Treatment (EPSDT). These visits are designed to promote physical, emotional, and cognitive health. Six visits are recommended for the first year of life, 3 for the second year. We hypothesized that children with the recommended visits in the first 2 years of life would be more likely than others to be ready for school when they finish kindergarten. METHODS: We studied children insured by Medicaid in South Carolina, born during 2000 through 2002 (n = 21,998). Measures included the number of EPSDT visits in the first 2 years of life and an assessment of school readiness conducted at the end of kindergarten. We used logistic regression to examine the adjusted association between having the recommended visits and school readiness, controlling for characteristics of mothers, infants, prenatal care and delivery, and residence area. RESULTS: Children with the recommended visits had 23% higher adjusted odds of being ready for school than those with fewer visits. CONCLUSION: EPSDT may contribute to school readiness for children insured by Medicaid. Children having fewer than the recommended EPSDT visits may benefit from school readiness programs. PMID- 22677163 TI - A phase II prospective, non-comparative assessment of a new silver sodium carboxymethylcellulose (AQUACEL((r)) Ag BURN) glove in the management of partial thickness hand burns. AB - BACKGROUND: Nylon-reinforced silver sodium carboxymethylcellulose (AQUACEL((r)) Ag BURN) dressings were developed to be pliable and conforming for the management of partial-thickness burns. This study evaluated the AQUACEL((r)) Ag BURN glove for the management of hand burns. METHODS: This 21-day, phase II, prospective, non-comparative study included 23 patients with partial-thickness hand burn of at least two fingers. The AQUACEL((r)) Ag BURN glove was applied to one hand and could remain in place up to 21 days until clinically indicated to change the glove. Dressings were evaluated 1, 2, 4, 6, 8, 14, and 21 days after initial application. Safety was the primary study endpoint. RESULTS: Sixteen (70%) hand burns re-epithelialized fully over a mean of 15.6 days. Initial application was easy/very easy for 20 (87%) patients. Mean time for initial dressing application was 5.4 min. At final evaluation, most patients gave ratings of excellent/good for conformability (91%), overall glove performance (74%), and appropriateness of sizes (83%). Mean pain score from 0 (none) to 10 (worst imaginable) was 3.43 at baseline; during the study, mean scores were 1.15 at rest and 2.29 during movement. Of 61 glove removals, most (72%) were easy/very easy, and 12% had fallen off. Adverse events (wound site or elsewhere) occurred in 15 (65%) patients. Treatment-related adverse events were wound pain (17%), maceration (9%), and stiff fingers (4%). CONCLUSIONS: The AQUACEL((r)) Ag BURN glove was well tolerated in the management of partial-thickness hand burn. Many patients used only one glove. When glove changes were required, they were usually quick and easy. PMID- 22677160 TI - Construction of a multisite DataLink using electronic health records for the identification, surveillance, prevention, and management of diabetes mellitus: the SUPREME-DM project. AB - INTRODUCTION: Electronic health record (EHR) data enhance opportunities for conducting surveillance of diabetes. The objective of this study was to identify the number of people with diabetes from a diabetes DataLink developed as part of the SUPREME-DM (SUrveillance, PREvention, and ManagEment of Diabetes Mellitus) project, a consortium of 11 integrated health systems that use comprehensive EHR data for research. METHODS: We identified all members of 11 health care systems who had any enrollment from January 2005 through December 2009. For these members, we searched inpatient and outpatient diagnosis codes, laboratory test results, and pharmaceutical dispensings from January 2000 through December 2009 to create indicator variables that could potentially identify a person with diabetes. Using this information, we estimated the number of people with diabetes and among them, the number of incident cases, defined as indication of diabetes after at least 2 years of continuous health system enrollment. RESULTS: The 11 health systems contributed 15,765,529 unique members, of whom 1,085,947 (6.9%) met 1 or more study criteria for diabetes. The nonstandardized proportion meeting study criteria for diabetes ranged from 4.2% to 12.4% across sites. Most members with diabetes (88%) met multiple criteria. Of the members with diabetes, 428,349 (39.4%) were incident cases. CONCLUSION: The SUPREME-DM DataLink is a unique resource that provides an opportunity to conduct comparative effectiveness research, epidemiologic surveillance including longitudinal analyses, and population-based care management studies of people with diabetes. It also provides a useful data source for pragmatic clinical trials of prevention or treatment interventions. PMID- 22677164 TI - Quantitative evaluation of MRI-based tracking of ferritin-labeled endogenous neural stem cell progeny in rodent brain. AB - Endogenous neural stem cells have the potential to facilitate therapy for various neurodegenerative brain disorders. To increase our understanding of neural stem and progenitor cell biology in healthy and diseased brain, methods to label and visualize stem cells and their progeny in vivo are indispensable. Iron oxide particle based cell-labeling approaches enable cell tracking by MRI with high resolution and good soft tissue contrast in the brain. However, in addition to important concerns about unspecific labeling and low labeling efficiency, the dilution effect upon cell division is a major drawback for longitudinal follow-up of highly proliferating neural progenitor cells with MRI. Stable viral vector mediated marking of endogenous stem cells and their progeny with a reporter gene for MRI could overcome these limitations. We stably and efficiently labeled endogenous neural stem/progenitor cells in the subventricular zone in situ by injecting a lentiviral vector expressing ferritin, a reporter for MRI. We developed an image analysis pipeline to quantify MRI signal changes at the level of the olfactory bulb as a result of migration of ferritin-labeled neuroblasts along the rostral migratory stream. We were able to detect ferritin-labeled endogenous neural stem cell progeny into the olfactory bulb of individual animals with ex vivo MRI at 30 weeks post injection, but could not demonstrate reliable in vivo detection and longitudinal tracking of neuroblast migration to the OB in individual animals. Therefore, although LV-mediated labeling of endogenous neural stem and progenitor cells resulted in efficient and stable ferritin-labeling of stem cell progeny in the OB, even with quantitative image analysis, sensitivity remains a limitation for in vivo applications. PMID- 22677165 TI - Glioblastoma: therapeutic challenges, what lies ahead. AB - Glioblastoma (GBM) is one of the most aggressive human cancers. Despite current advances in multimodality therapies, such as surgery, radiotherapy and chemotherapy, the outcome for patients with high grade glioma remains fatal. The knowledge of how glioma cells develop and depend on the tumor environment might open opportunities for new therapies. There is now a growing awareness that the main limitations in understanding and successfully treating GBM might be bypassed by the identification of a distinct cell type that has defining properties of somatic stem cells, as well as cancer-initiating capacity - brain tumor stem cells, which could represent a therapeutic target. In addition, experimental studies have demonstrated that the combination of antiangiogenic therapy, based on the disruption of tumor blood vessels, with conventional chemotherapy generates encouraging results. Emerging reports have also shown that microglial cells can be used as therapeutic vectors to transport genes and/or substances to the tumor site, which opens up new perspectives for the development of GBM therapies targeting microglial cells. Finally, recent studies have shown that natural toxins can be conjugated to drugs that bind to overexpressed receptors in cancer cells, generating targeted-toxins to selectively kill cancer cells. These targeted-toxins are highly effective against radiation- and chemotherapy resistant cancer cells, making them good candidates for clinical trials in GBM patients. In this review, we discuss recent studies that reveal new possibilities of GBM treatment taking into account cancer stem cells, angiogenesis, microglial cells and drug delivery in the development of new targeted-therapies. PMID- 22677166 TI - Promoting protective factors for young adolescents: ABCD Parenting Young Adolescents Program randomized controlled trial. AB - This study examined the efficacy of a program for parents of young adolescents combining behavioral family intervention with acceptance-based strategies. 180 parents were randomly allocated to a 6-session group ABCD Parenting Young Adolescent Program or wait-list condition. Completer analysis indicated parents in the intervention reported significantly higher adolescent prosocial behaviors (p = 0.020), lower conduct problems (p = 0.048) and total difficulties (p = 0.041). These parents also reported lower stress associated with adolescent moodiness (p = 0.032), parent life-restriction (p < 0.001), adult-relations (p < 0.001), social isolation (p = 0.012), incompetence/guilt (p < 0.001), lower stress in the parenting domain (p < 0.001) and lower overall stress (p = 0.003) relative to the control condition following the intervention period. No other statistically significant differences were evident (p < 0.05). Results of intention-to-treat analyses were similar. Greater reliable clinically significant change was also achieved for the intervention condition. Participants reported high satisfaction with all elements of the ABCD program. Results suggest the program may assist parents of young adolescents to promote or maintain protective factors in their families. Australian and New Zealand Clinical Trials Registry: ANZCTRN12609000194268. PMID- 22677167 TI - Phylogeny, rate variation, and genome size evolution of Pelargonium (Geraniaceae). AB - The phylogeny of 58 Pelargonium species was estimated using five plastid markers (rbcL, matK, ndhF, rpoC1, trnL-F) and one mitochondrial gene (nad5). The results confirmed the monophyly of three major clades and four subclades within Pelargonium but also indicate the need to revise some sectional classifications. This phylogeny was used to examine karyotype evolution in the genus: plotting chromosome sizes, numbers and 2C-values indicates that genome size is significantly correlated with chromosome size but not number. Accelerated rates of nucleotide substitution have been previously detected in both plastid and mitochondrial genes in Pelargonium, but sparse taxon sampling did not enable identification of the phylogenetic distribution of these elevated rates. Using the multigene phylogeny as a constraint, we investigated lineage- and locus specific heterogeneity of substitution rates in Pelargonium for an expanded number of taxa and demonstrated that both plastid and mitochondrial genes have had accelerated substitution rates but with markedly disparate patterns. In the plastid, the exons of rpoC1 have significantly accelerated substitution rates compared to its intron and the acceleration was mainly due to nonsynonymous substitutions. In contrast, the mitochondrial gene, nad5, experienced substantial acceleration of synonymous substitution rates in three internal branches of Pelargonium, but this acceleration ceased in all terminal branches. Several lineages also have dN/dS ratios significantly greater than one for rpoC1, indicating that positive selection is acting on this gene, whereas the accelerated synonymous substitutions in the mitochondrial gene are the result of elevated mutation rates. PMID- 22677168 TI - A neuronal transmembrane protein LRFN4 complexes with 14-3-3s and NCK1 to induce morphological change in monocytic cells via Rac1-mediated actin cytoskeleton reorganization. AB - We previously reported that leucine-rich repeat and fibronectin type III domain containing 4 (LRFN4) functioned in migration and morphological change (i.e. cell elongation) of monocytic cells. Here, we examined a molecular mechanism regulating LRFN4-mediated cell elongation. We found that 14-3-3 and NCK proteins complexed with LRFN4, and they were involved in LRFN4-mediated cell elongation. We also identified the regions of LRFN4 interacting with NCK1 and 14-3-3s. Finally, we demonstrated that a Rac1 small GTPase was involved in LRFN4-mediated cell elongation. These results indicated that LRFN4 complexed with 14-3-3s and NCK1 to mediate elongation in monocytic cells via Rac-1-mediated actin cytoskeleton reorganization. PMID- 22677169 TI - Down-regulated miR-625 suppresses invasion and metastasis of gastric cancer by targeting ILK. AB - Accumulating evidence has shown that microRNAs are involved in multiple processes in cancer development and progression. Here, we report that expression of miR-625 is significantly down-regulated and negatively correlated with lymph node metastasis in gastric cancer. miR-625 significantly inhibits invasion and metastasis of gastric cancer cells both in vitro and in vivo. Moreover, we identify that ILK is a direct target gene for miR-625 and knockdown of ILK has a phenocopy of overexpression of miR-625. Taken together, our findings suggest that miR-625 plays an important role in the mechanism of tumor metastasis. PMID- 22677170 TI - Cyclic AMP-dependent protein kinase regulates 9G8-mediated alternative splicing of tau exon 10. AB - Alternative splicing of tau exon 10 generates tau isoforms with three or four microtubule-binding repeats, named 3R- or 4R-tau. Normal adult human brain expresses equal levels of them. Imbalance of 3R-tau and 4R-tau associates with several tauopathies. Splicing factor 9G8 suppresses tau exon 10 inclusion and its function is regulated by phosphorylation. Here, we found that cyclic AMP dependent protein kinase (PKA) phosphorylated 9G8. The catalytic subunits alpha and beta of PKA interacted with 9G8, and activation of PKA enhanced the interaction. Up-regulation of PKA activity prevented 9G8 from inhibition of tau exon 10 inclusion. These findings provide novel insights into the regulation of tau exon 10 splicing and further our understanding of neurodegeneration associated with dysregulation of tau exon 10 splicing. PMID- 22677171 TI - Alendronate promotes plasmin-mediated MMP-9 inactivation by exposing cryptic plasmin degradation sites within the MMP-9 catalytic domain. AB - Irreversible MMP-9 inhibition is considered a significant therapeutic goal in inflammatory, vascular and tumour pathology. We report that divalent cation chelators Alendronate and EDTA not only directly inhibited MMP-9 but also promoted irreversible plasmin-mediated MMP-9 inactivation by exposing cryptic plasmin-degradation sites within the MMP-9 catalytic-domain and producing an inhibitory hemopexin-domain fragment. This effect was also observed using MDA-MB 231 breast cancer cells, which activated exogenous plasminogen to degrade endogenous proMMP-9 in the presence of Alendronate or EDTA. Degradation-mediated inactivation of proMMP-9 occurred in the absence of transient activation, attesting to the incapacity of plasmin to directly activate proMMP-9 and direct MMP-9 inhibition by Alendronate and EDTA. Our study provides a novel rational for therapeutic Alendronate use in MMP-9-dependent pathology characterised by plasminogen activation. PMID- 22677172 TI - Glycolytic cancer cells lacking 6-phosphogluconate dehydrogenase metabolize glucose to induce senescence. AB - We show that knockdown of 6-phosphogluconate dehydrogenase (6PGD) of the pentose phosphate pathway (PPP) inhibits growth of lung cancer cells by senescence induction. This inhibition is not due to a defect in the oxidative PPP per se. NADPH and ribose phosphate production are normal in 6PGD knockdown cells and shutdown of PPP by knockdown of glucose-6-phosphate dehydrogenase (G6PD) has little effect on cell growth. Moreover, 6PGD knockdown cells can proliferate when the PPP is bypassed by using fructose instead of glucose in medium. Significantly, G6PD knockdown rescues proliferation of cells lacking 6PGD, suggesting an accumulation of growth inhibitory glucose metabolics in cells lacking 6PGD. Therefore, 6PGD inhibition may provide a novel strategy to treat glycolyic tumors such as lung cancer. PMID- 22677173 TI - Inhibitory effect of SPE-39 due to tyrosine phosphorylation and ubiquitination on the function of Vps33B in the EGF-stimulated cells. AB - Although SPE-39 is a binding protein to Vps33B that is one of the subunit in the mammalian HOPS complex, the elements of SPE-39 function remain unknown. Here, we show that tyrosine phosphorylation of SPE-39 following EGF stimulation plays a role in the stability of SPE-39 itself. Ubiquitination of the C-terminal region of SPE-39 was also elevated in response to EGF stimulation, and this process was regulated by the phosphorylation of Tyr-11 in SPE-39. However, association of Vps33B with SPE-39 inhibited the elevation of ubiquitination of SPE-39 following EGF stimulation, which might be responsible for the stabilization of SPE-39. Furthermore, an opposing functional relationship between SPE-39 and Vps33B on the downregulation of the EGF receptor was observed in EGF-stimulated COS-7 cells. PMID- 22677174 TI - Adaptive time-varying detrended fluctuation analysis. AB - Detrended fluctuation analysis (DFA) is a technique commonly used to assess and quantify the presence of long-range temporal correlations (LRTCs) in neurophysiological time series. Convergence of the method is asymptotic only and therefore its application assumes a constant scaling exponent. However, most neurophysiological data are likely to involve either spontaneous or experimentally induced scaling exponent changes. We present a novel extension of the DFA method that permits the characterisation of time-varying scaling exponents. The effectiveness of the methodology in recovering known changes in scaling exponents is demonstrated through its application to synthetic data. The dependence of the method on its free parameters is systematically explored. Finally, application of the methodology to neurophysiological data demonstrates that it provides experimenters with a way to identify previously un-recognised changes in the scaling exponent in the data. We suggest that this methodology will make it possible to go beyond a simple demonstration of the presence of scaling to an appreciation of how it may vary in response to either intrinsic changes or experimental perturbations. PMID- 22677176 TI - Focalizing electrical neural stimulation with penetrating microelectrode arrays: a modeling study. AB - Penetrating neural probes are considered for neuroprosthetic devices to restore sensory or motor functions of the CNS using electrical neural microstimulation. These multielectrode systems require optimal electrode configurations to allow precise and focused tissue activation. Combining a finite element model of the spinal cord and compartmentalized models of both simple and complex neuron morphologies, we evaluated the use of the "ground surface" configuration, which consists in the integration of a conductive layer on the front side of electrode shanks, for the return of the stimulation current. Compared to the classical monopolar and bipolar configurations, this strategy resulted in a focalization of both the potential field and the threshold-distance curves. The improvement in focalization was highest for lowest impedance of the ground surface. Moreover, the gain in focality was highest on the side of the shank opposite to the electrode, so that only the neurons located in front of stimulation electrode were activated. This focalizing strategy will allow the design of new microstimulation paradigms aiming at precisely targeting the CNS with complex spatio-temporal stimulation patterns, which could benefit to future stimulation based neuroprosthesis. PMID- 22677175 TI - Wireless implantable micro-stimulation device for high frequency bilateral deep brain stimulation in freely moving mice. AB - Although deep brain stimulation (DBS) has been proven to be an effective treatment for several neuropsychiatric disorders, such as Parkinson's disease, the underlying working mechanisms are still largely unknown. Behavioral animal models are essential in examining the working mechanisms of DBS and especially mouse models are necessary to investigate the genetic component underlying specific behaviors related to psychiatric diseases. Unfortunately, currently available stimulation devices are unsuitable to test behavior in freely-moving mice. As such, no DBS studies in behaving mice have been reported thus far. In order to overcome this limitation we have developed a new light-weight wireless implantable micro stimulator device for mice that delivers biphasic pulse patterns to two individual electrode pairs, mimicking partly the clinical situation. This paper describes in detail the bench-top validation and in vivo implementation of this device. The results in this study indicate that the wireless implantable stimulator in mice reliably delivers continuous bilateral stimulation, importantly, does not restrict the animals mobility and hygiene (grooming behavior). In vivo testing furthermore showed that stimulation of the mice ventral striatum yields similar results as previously shown by others in rats where conventional deep brain stimulation techniques were used. This newly designed device can now be used in the highly needed DBS behavioral studies in mice, to further investigate the underlying mechanisms of DBS in behavioral animal models for psychiatric disorders. PMID- 22677177 TI - Risk factors for intramammary infections and subclinical mastitis in post-partum dairy heifers. AB - The prevalence of intramammary infections (IMI) and subclinical mastitis (SCM) in 436 German Holstein heifers was put in relation with clinical findings of the udder and data regarding individual rearing and housing conditions of the animals. The clinical examination took place on the day of the livestock auction (at approximately 41 d in milk, DIM). On that day, 31% of the heifers had IMI in at least one quarter, and 18% of all quarters were infected. Coagulase-negative staphylococci were the most prevalent bacteria isolated, accounting for 68% of the positive samples. Data were analysed by logistic regression. Criteria such as 'juvenile intersucking', 'teats shorter than 35 mm', 'teats with a diameter <18 mm' and 'udder oedema at the day of the auction' were associated with IMI in heifers during the first 41 DIM. Loose-housing systems during pregnancy (as opposed to tie-stalls), juvenile intersucking, clinical mastitis during the first week after calving, teat diameters <18 mm, and employing organic bedding material in the stables before calving were associated with subclinical mastitis. PMID- 22677178 TI - Rotavirus immune responses and correlates of protection. AB - Selected topics in the field of rotavirus immunity are reviewed focusing on recent developments that may improve efficacy and safety of current and future vaccines. Rotaviruses (RVs) have developed multiple mechanisms to evade interferon (IFN)-mediated innate immunity. Compared to more developed regions of the world, protection induced by natural infection and vaccination is reduced in developing countries where, among other factors, high viral challenge loads are common and where infants are infected at an early age. Studies in developing countries indicate that rotavirus-specific serum IgA levels are not an optimal correlate of protection following vaccination, and better correlates need to be identified. Protection against rotavirus following vaccination is substantially heterotypic; nonetheless, a role for homotypic immunity in selection of circulating postvaccination strains needs further study. PMID- 22677179 TI - [Influence of blood pressure variability during office visit on the estimation of blood pressure control in treated hypertensive patients]. AB - OBJECTIVE: To evaluate the variability in blood pressure observed during office visit in treated hypertensive patients and its consequences on the diagnosis of controlled hypertension. METHOD: The medical records of 144 subjects seen consecutively in a hypertension excellence center were extracted from a computerized medical database including hypertension subjects treated and followed-up for at least one year. BP measured with an automatic device (four consecutives measurements at 2min intervals) where compared to BP values of home BP performed in the previous week's visit. Thresholds were 140/90mmHg for office BP and 135/85mmHg for HBP. RESULTS: The population has the following characteristics: age 62 years with 26% over 70 years, treated with a monotherapy (33%), bitherapy (35%), triple therapy (17%), quadri-therapy or more (8%). A white coat effect SBP above 20mmHg was noted in 32% of patients when BP at 2min is taken and in 2% when BP at 8min is taken (P<0.01). After 8min, a masked effect is noted in 16% for SBP above 20mmHg and in 44% for DBP above 10mmHg. White coat hypertension or masked hypertension was noted in 40% or 16% respectively (BP 2min) and in 5% or 29% (BP 8min) in treated hypertensive. CONCLUSION: In treated hypertensive, office BP measured by an automatic device shows significant variability. When the BP is taken with an automatic device, measures taken after 8minutes of rest avoid the misleading effects of white coat effect, but the masked hypertension is present in nearly one third of the subjects. The use of AMT for monitoring hypertensive patients is the best way to monitor treatment efficacy. PMID- 22677180 TI - [Factors associated with poor blood pressure control in hypertensive black Africans: cross-sectional study of 456 hypertensive patients from Burkina Faso]. AB - INTRODUCTION: Hypertension in black is more frequent with early onset and clinically more severe. The blood pressure control and the decrease of global cardiovascular risk are two main goals of the treatment of hypertension. The objectives of this study were to determine the proportion of uncontrolled hypertension in hypertensive patients followed as outpatients and to investigate the factors associated with poor control. PATIENTS AND METHODS: This is a descriptive cross-sectional study including 456 hypertensive patients known and followed as outpatients. Blood pressure measurement was performed between 8 am and 12 noon both arms in the supine position, after a compliance averaging 8 minutes of rest. We searched for conventional cardiovascular risk factors (age superior or equal to 45 years for men and superior or equal to 55 for women, physical inactivity, overweight/obesity, smoking, diabetes and dyslipidemia) and calculated the global cardiovascular risk according to the Framingham model. Was regarded as uncontrolled high blood pressure SBP superior or equal to 140 mmHg and/or DBP superior or equal to 90 mmHg. Univariate analysis and multivariate logistic regression (using SPSS program version 17) were conducted to look for factors associated with poor blood pressure control. RESULTS: We recruited 456 hypertensive patients including 259 women (56.8%). Modifiable cardiovascular risk factors also hypertension were dominated by dyslipidemia (29.8%) and diabetes (24.6%). The global cardiovascular risk calculated using the Framingham model was low in 21.3%, moderate in 34.0%, high in 24.8% and very high in 19.9% of cases. The proportion of uncontrolled hypertension was 54.2% (n=247 including 126 women and 121 men). This poor blood pressure control was associated (multivariate analysis) at age superior or equal to 60 years, low socioeconomic status, high to very high cardiovascular risk, antihypertensive monotherapy, treatment duration superior or equal to 10 years, an associated treatment and non-compliance therapy. CONCLUSION: More than half of hypertensive patients in our study were not adequately controlled on antihypertensive therapy. Factors of poor control were age superior or equal to 60 years, low socioeconomic status, high to very high cardiovascular risk, antihypertensive monotherapy, treatment duration superior or equal to 10 years, an associated treatment and non-compliance therapy. PMID- 22677181 TI - [Frequency of hypertension resistant to treatment and indication for renal denervation]. AB - OBJECTIVE: To evaluate in hypertensive patients followed in a specialized hypertension unit, the prevalence of subjects uncontrolled despite triple therapy including a diuretic. The aim is to estimate the percentage of hypertensive patients with an indication to renal denervation. METHOD: From a database of computerized medical records of a unit specialized in hypertension, it was extracted 144 consecutive cases of subjects treated and followed for at least 1year and having had a home pressure monitoring (HPM) on treatment, and if necessary a work-up for a secondary hypertension. The blood pressure (BP) was evaluated in office by automated method (after 2 and 8minutes) and with HPM (average of three measurements in the morning and evening for three consecutive days). RESULTS: The population has the following characteristics: age 62 with 26% over 70years, treated dyslipidemia (39%), treated diabetes (11%), adrenal hypertension treated medically (14%), severe renal failure (3%). The means of treatment are: a monotherapy (33%), bitherapy (35%), triple therapy (17%), quadritherapy (7%), pentatherapy or more (1%), spironolactone (45%), thiazide diuretics (49%). The uncontrolled hypertension was observed in 26% if the BP is evaluated with HPM, in 52% if the BP is evaluated at the office after 2minutes of rest and 7% if the BP is evaluated after 8minutes of rest (P<0.01). In patients treated with at least a tritherapy in association with a diuretic, an uncontrolled hypertension was observed in 5% if the BP is evaluated with HPM. Failure to control for the SBP is the cause of 80% of resistant hypertension. CONCLUSION: The frequency of resistant hypertension is 5% of hypertensive patients followed in a specialized hypertension unit when guidelines are applied in the case of uncontrolled hypertension. These results indicate that the indication for renal denervation affects only a small percentage of patients treated for hypertension. PMID- 22677182 TI - [Prevalence of obesity in school children in Ivory Coast]. AB - BACKGROUND: According to the World Health Organization, an increased prevalence of hypertension in children is observed since several years due to an epidemic of childhood obesity. What is the extent of this epidemic in our African context? METHOD: We conducted a prospective descriptive study of pupils encountered in primary and secondary schools of the district of Abidjan from May 3 to June 1st 2010. A sample of 2038 pupils aged 6 to 18 years was randomly selected. Overweight in pupils was assessed by body mass index (BMI). RESULTS: There were 1182 girls (58%) and 856 boys (42%) whose average age was 12.7+/-3.6 years. The average weight was 42.6kg+/-16 (range 14.6 to 106.2kg), the average size was 1.48m+/-0.19 (range 1 to 1.95m). BMI was 17.2kg/m(2)+/-3.7 (range 14.6-35.7). The prevalence of obesity was of 5%. In addition, 4% of the students were overweight, 39% extremely thin, 25% thin and 27% normal. Obesity was more common in girls (6.8%) than boys (1.8%). The prevalence of obesity in hypertensives was 16%. BMI influenced the systolic and diastolic blood pressure in both sexes (P<0.001 in both cases). CONCLUSION: Childhood obesity exists in a country like the Ivory Coast where wealthness is far from generalized. A well-organized management of childhood obesity is necessary to avoid complications such as hypertension. PMID- 22677183 TI - [Oxydative stress and beneficial effect of sodium restriction on kidney damage associated with insulin resistance in rats]. AB - The aim of this work was to evaluate the influence of dietary sodium restriction on metabolic and renal changes associated with insulin resistance. At 8 weeks of age, rats received either a diet containing 60% fructose with or without sodium or a standard diet for 12 weeks. The insulin resistance and albuminuria induced by the high fructose diet were associated with a fibrosis and increase in oxidative stress in the kidney. The low salt diet prevented insulin resistance, renal fibrosis and albuminuria induced by the fructose diet. These beneficial effects on the kidney were associated with a decrease in kidney NADPH oxidase activity. Oxidative status is probably one of the major targets of the favourable effect of salt restriction on renal changes associated with insulin resistance, without excluding the involvement of other mechanisms. PMID- 22677184 TI - Early events regulating immunity and pathogenesis during Listeria monocytogenes infection. AB - Listeria monocytogenes (Lm) is both a life-threatening pathogen of humans and a model organism that is widely used to dissect the mechanisms of innate and adaptive immune resistance to infection. Specific aspects of the immune response to systemic Lm infection can be protective, neutral, or in some cases deleterious. In this review, we seek to provide an overview of the early events during Lm infection that dictate or regulate host innate and adaptive immune responses. We highlight several recent developments that add to our understanding of the complex interplay between inflammatory responses, host susceptibility to infection, and the development of protective immunity. PMID- 22677185 TI - Antibiotics, microbiota, and immune defense. AB - The gastrointestinal tract microbiota contributes to the development and differentiation of the mammalian immune system. The composition of the microbiota affects immune responses and affects susceptibility to infection by intestinal pathogens and development of allergic and inflammatory bowel diseases. Antibiotic administration, while facilitating clearance of targeted infections, also perturbs commensal microbial communities and decreases host resistance to antibiotic-resistant microbes. Here, we review recent advances that begin to define the interactions between complex intestinal microbial populations and the mammalian immune system and how this relation is perturbed by antibiotic administration. We further discuss how antibiotic-induced disruption of the microbiota and immune homeostasis can lead to disease and we review strategies to restore immune defenses during antibiotic administration. PMID- 22677187 TI - Development of antigen cross-presentation capacity in dendritic cells. AB - Cross-presentation by dendritic cells (DCs) of exogenous antigens on MHC class I is important for the generation of immune responses to intracellular pathogens, as well as for maintenance of self tolerance. In mice, the CD8(+) DC lineage is specialised for this role. However, DCs of this lineage are not born with cross presentation capacity. Several studies have demonstrated that it must be induced as a later developmental step by cytokines such as granulocyte macrophage colony stimulating factor (GM-CSF), or by microbial products such as toll-like receptor (TLR) ligands. Increased cross-presentation capacity is thus induced in peripheral CD8 lineage DCs during inflammation or infection. However, this capacity is already fully developed in steady-state thymic CD8(+) DCs, in accordance with their role in the deletion of self-reactive developing T cells. PMID- 22677188 TI - Special issue: collaborative evaluation--theory and practice. PMID- 22677186 TI - CD22 and Siglec-G in B cell function and tolerance. AB - The immune system has evolved into two main arms: the primitive innate arm that is the first line of defense but relatively short-lived and broad acting; and the advanced adaptive arm that generates immunological memory, allowing rapid, specific recall responses. T cell-independent type-2 (TI-2) antigens (Ags) invoke innate immune responses. However, due to its 'at the ready' nature, how the innate arm of the immune system maintains tolerance to potentially abundant host TI-2 Ags remains elusive. Therefore, it is important to define the mechanisms that establish innate immune tolerance. This review highlights recent insights into B cell tolerance to theoretical self TI-2 Ags, and examines how the B cell restricted sialic acid binding Ig-like lectins (Siglecs), CD22 and Siglec-G, might contribute to this process. PMID- 22677189 TI - Fluorescent viral nanoparticles with stable in vitro and in vivo activity. AB - We synthesized fluorescent capsid nanoparticles (FCNPs) by genetically inserting fluorescent protein (FP) (DsRed or eGFP) into each of 240 surface spike tips of hepatitis B virus (HBV) capsid particles. That is, when expressed in E. coli, FCNPs formed spherical nanoparticles with uniform diameter of about 40 nm owing to the self-assembly function of HBV core protein (i.e. basic assembly unit of capsid) and were successfully purified through Ni(+2) affinity- and sucrose gradient based purification. We also added the glycine-rich fexible linker peptides in between DsRed (or eGFP) and capsid to reduce fluorescence quenching among the densely displayed DsReds (or eGFPs) on the capsid surface. As compared to cognate fluorescent monomer proteins, it is notable that FCNPs showed a significantly amplified (160-170-fold) fluorescence intensity and enhanced conformational stability even in 50% serum solutin at 37 degrees C. The high conformational stability of FCNPs seems to result both from the highly stable structure of HBV capsid particles and from the well oriented insertion of fluorescent protein into capsid spike tip to keep native conformation of DsRed or eGFP. When estimated with continuous exposure to strong excitation light, FCNPs also showed much higher photostability than DsRed, eGFP, and a commonly used organic fluorescent dye, which happened presumably because the enhanced conformational stability of FCNPs significantly reduced photobleaching of fluorophores. Especially, it is notable that rFCNPs stably emitted high-level fluorescence inside mouse for a prolonged period, thereby showing high in vivo stability. The developed FCNPs are likely to have a great potential to be used as an effective and non-cytotoxic tool for in vivo optical imaging as well as in vitro fluorescent reporter in various biomolecular detection assays. PMID- 22677190 TI - Molecular mechanism of hypoxia-induced chondrogenesis and its application in in vivo cartilage tissue engineering. AB - Cartilage engineering is one of the most challenging issue in regenerative medicine, due to its limited self-ability to repair. Here, we assessed engineering of cartilage tissue starting from human bone marrow (hBM) stem cells under hypoxic environment and delineated the mechanism whereby chondrogenesis could be conducted without addition of exogenous growth factors. hBM stem cells were cultured in alginate beads and chondrogenesis was monitored by chondrocyte phenotypic markers. Activities and roles of Sox and HIF-1alpha transcription factors were investigated with complementary approaches of gain and loss of function and provided evidences that HIF-1alpha is essential for hypoxic induction of chondrogenesis. Thereafter, hBM cells and human articular chondrocytes (HAC) underwent chondrogenesis by 3D and hypoxic culture for 7 days or by ectopic expression of HIF-1alpha. After subcutaneous implantation of 3 weeks into athymic mice, tissue analysis showed that hypoxia or HIF-1alpha overexpression is effective and sufficient to induce chondrocyte phenotype in hBM cells, without use of exogenous growth factors. Therefore, this study brings interesting data for a simple and affordable system in biotechnology of cartilage engineering. PMID- 22677191 TI - Role of angiogenesis in the pathogenesis of cancer. AB - It has been recognized for decades that angiogenesis is an important event in tumor growth and metastasis; the concept of the "angiogenic switch," whereby tumors acquire the ability to grow exponentially and disseminate beyond their primary site, is one of the central components in our understanding of cancer. A vast network of signaling molecules and receptors that are involved in the regulation of angiogenesis have been identified and characterized; most notably, the vascular endothelial growth factor (VEGF) family. Indeed, the VEGF family of growth factors and receptors has become a prototype for our understanding of angiogenesis during early development and in pathological conditions such as cancer. The specific inhibition of key regulatory molecules including VEGF-A (such as with bevacizumab treatment) has been recognized as a useful strategy to reduce tumor growth and progression in several tumor types. Nevertheless, the contribution of other members of the VEGF family, other signaling pathways, and also endogenous angiogenic inhibitors to tumor angiogenesis, is beginning to emerge. The diversity of pathways and molecules involved in the regulation of angiogenesis in both normal development and cancer will likely offer many more prospects for successful therapeutic intervention. PMID- 22677192 TI - Effects of blood pressure lowering on cardiovascular outcomes in different cardiovascular risk groups among participants with type 2 diabetes. AB - AIMS: To asses differences in treatment effects of a fixed combination of perindopril-indapamide on major clinical outcomes in patients with type 2 diabetes across subgroups of cardiovascular risk. METHODS: 11,140 participants with type 2 diabetes, from the ADVANCE trial, were randomized to perindopril indapamide or matching placebo. The Framingham equation was used to calculate 5 year CVD risk and to divide participants into two risk groups, moderate-high risk (<25% and no history of macrovascular disease), very high risk (>25% and/or history of macrovascular disease). Endpoints were macrovascular and microvascular events. RESULTS: The mean age of participants was 66 years (42.5% female). 1000 macrovascular and 916 microvascular events were recorded over follow-up of 4.3 years. Relative treatment effects were similar across risk groups, (all P-values for heterogeneity >=0.38). Hazard ratios for combined macro- and microvascular events were 0.89 (0.77-1.03) for the moderate-high risk and 0.92 (0.81-1.03) for the very high risk. Absolute treatment effects tended to be greater in the high risk groups although differences were not statistically significant (P>0.05). CONCLUSIONS: Relative effects of blood pressure lowering with perindopril indapamide on cardiovascular outcomes were similar across risk groups whilst absolute effects trended to be greater in the high risk group. PMID- 22677193 TI - Dysregulated Kruppel-like factor 4 and vitamin D receptor signaling contribute to progression of hepatocellular carcinoma. AB - BACKGROUND & AIMS: Kruppel-like factor 4 (KLF4) is a transcription factor and putative tumor suppressor. However, little is known about its effects in hepatocellular carcinogenesis. We investigated the clinical significance, biologic effects, and mechanisms of dysregulated KLF4 signaling. METHODS: We performed microarray analysis of hepatocellular carcinoma (HCC) tissues. We used molecular biology analyses and animal models to evaluate activation and function of KLF4-vitamin D receptor (VDR) pathway. RESULTS: Expression of KLF4 protein was decreased or lost in primary HCC samples, in particular, lymph node metastases, compared with normal liver tissues. Loss of KLF4 from primary tumors was significantly associated with reduced survival time and was identified as a prognostic marker. Most human HCC cell lines had losses or substantial decreases in levels of KLF4. Exogenous expression of KLF4 in HCC cells upregulated expression of mesenchymal-epithelial transition (MET) and inhibited their migration, invasion, and proliferation in vitro. When these cells were injected into mice, tumors grew more slowly and metastasis was inhibited, compared with HCC cells that did not express KLF4. VDR is a direct transcriptional target of KLF4; we identified 2 sites in the VDR promoter that bound specifically to KLF4. Increased expression of VDR sensitized tumor cells to the inhibitory effects of vitamin D. CONCLUSIONS: KLF4 binds to the promoter of VDR to regulate its expression; levels of KLF4 are reduced and levels of VDR are increased in HCC cell lines and primary tumor samples. Expression of KLF4 in HCC cells sensitizes them to the anti-proliferative effects of VD3. This pathway might be manipulated to prevent or treat liver cancer. PMID- 22677194 TI - Interferon-gamma-stimulated genes, but not USP18, are expressed in livers of patients with acute hepatitis C. AB - BACKGROUND & AIMS: Approximately 50% of patients with chronic hepatitis C (CHC) have a sustained virologic response to treatment with pegylated interferon (pegIFN)-alpha and ribavirin. Nonresponse to treatment is associated with constitutively increased expression of IFN-stimulated genes (ISGs) in the liver. Treatment of patients with acute hepatitis C (AHC) is more effective, with sustained virologic response rates greater than 90%. We investigated mechanisms of the different responses of patients with CHC and AHC to pegIFN-alpha therapy. METHODS: We analyzed IFN signaling and ISG expression in liver samples from patients with AHC, patients with CHC, and individuals without hepatitis C (controls) using microarray, immunohistochemical, and protein analyses. Findings were compared with those from primary human hepatocytes stimulated with IFN-alpha or IFN-gamma, as reference sets. RESULTS: Expression levels of hundreds of genes, primarily those regulated by IFN-gamma, were altered in liver samples from patients with AHC compared with controls. Expression of IFN-gamma-stimulated genes was induced in liver samples from patients with AHC, whereas expression of IFN-alpha-stimulated genes was induced in samples from patients with CHC. In an expression analysis of negative regulators of IFN-alpha signaling, we did not observe differences in expression of suppresor of cytokine signaling 1 or SOCS3 between liver samples from patients with AHC and those with CHC. However, USP18 (another negative regulator of IFN-alpha signaling), was up-regulated in liver samples of patients with CHC that did not respond to therapy, but not in AHC. CONCLUSIONS: Differences in expression of ISGs might account for the greater response of patients with AHC, compared with those with CHC, to treatment with pegIFN-alpha and ribavirin. Specifically, USP18 is up-regulated in liver samples of patients with CHC that did not respond to therapy, but not in patients with AHC. PMID- 22677195 TI - RETRACTED: Obesity-induced increase in tumor necrosis factor-alpha leads to development of colon cancer in mice. AB - This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal).This article has been retracted at the request of the Editor-in-Chief and Deputy Editor-in-Chief following an investigation into the data that were presented in several figures within the article.A number of images used in this article are believed to be duplicated images. The authors stated that they inadvertently inserted images of the wrong blots in several of the figures, resulting in the duplications; however, they did not address all of the concerns raised. Because the editors were no longer confident in the conclusions of the article based on these incorrect data, a decision was made to retract the paper.All authors have been notified of this decision. The University of Campinas (UNICAMP) in Sao Paulo, Brazil was contacted regarding these concerns, but to date the journal has received no response. PMID- 22677197 TI - A screening model for low bone mass in elderly Japanese men using quantitative ultrasound measurements: Fujiwara-Kyo Study. AB - Screening for low bone mass is important to prevent fragility fractures in men as well as women, although men show a much lower prevalence of osteoporosis than women. The purpose of this study was to establish a screening model for low bone mineral density (BMD) using a quantitative ultrasound parameter and easily obtained objective indices for elderly Japanese men. We examined 1633 men (65-84 yr old) who were subjects of the Fujiwara-Kyo Study. Speed of sound (SOS) at the calcaneus was determined, and BMD was measured by dual-energy X-ray absorptiometry at the lumbar spine (LS), total hip (TH), and femoral neck (FN). Low BMD was defined as >1 standard deviation below the young adult mean, in accordance with World Health Organization criteria. We performed receiver operating characteristic (ROC) analysis to identify a better screening model incorporating SOS and determined the optimal cutoff value using Youden index. Prevalences of low BMD at the 3 skeletal sites were 27.8% (LS), 33.5% (TH), 48.6% (FN), and 43.3% at either LS or TH. The greatest area under the ROC curve (0.806, 95% confidence interval: 0.785-0.828) and smallest Akaike's information criterion were obtained in the multivariate model incorporating SOS, age, height, and weight for predicting low BMD at all skeletal sites. This model predicted low BMD at TH with the sensitivity of 0.726 and specificity of 0.739, whereas a similar model predicted low BMD at LS with much lower validity. We conclude that the multivariate model for TH could be used to screen for low BMD in elderly Japanese men. PMID- 22677196 TI - Age and sex differences in estimated tibia strength: influence of measurement site. AB - Variability in peripheral quantitative computed tomography (pQCT) measurement sites and outcome variables limit direct comparisons of results between studies. Furthermore, it is unclear what estimates of bone strength are most indicative of changes due to aging, disease, or interventions. The purpose of this study was to examine age and sex differences in estimates of tibia strength. An additional purpose of this study was to determine which tibia site or sites are most sensitive for detecting age and sex differences in tibia strength. Self identifying Caucasian men (n=55) and women (n=59) aged 20-59yr had their tibias measured with pQCT from 5% to 85% of limb length in 10% increments distal to proximal. Bone strength index, strength strain index (SSI), moments of inertia (Ip, Imax, and Imin), and strength-to-mass ratios (polar moment of inertia to total bone mineral content [BMC] ratio [Ip:Tot.BMC] and strength strain index to total BMC ratio [SSI:Tot.BMC]) were quantified. There were significant (p<0.01) site effects for all strength variables and strength-to-mass ratios. Site*sex interaction effects were significant (p<0.05) for all strength variables. Men had greater (p<0.01) values than women for all strength variables. Sex differences in Ip, Imax, Ip:Tot.BMC, SSI, and SSI:Tot.BMC ratios were the smallest at the 15% site and peaked at various sites, depending on variable. Site*age interactions existed for Imax, Ip:Tot.BMC, and SSI:Tot.BMC. There were significant age effects, Imax, Ip:Tot.BMC, and SSI:Tot.BMC, as values were the lowest in the 20 29 age group. Age and sex differences varied by measurement site and variable, and larger sex differences existed for moments of inertia than SSI. Strength-to mass ratios may reflect efficiency of the whole bone architecture. PMID- 22677198 TI - Bone loss in chronic hemiplegia: a longitudinal cohort study. AB - The purpose of this study was to evaluate hemiplegic stroke patients in terms of long-term changes in bone mineral density and related factors. We conducted a longitudinal cohort study, involving 57 first-stroke patients (40 males) with chronic hemiplegia (for more than 12mo), at a university rehabilitation center in the city of Sao Paulo, Brazil. Bone loss, body composition, lean mass, and fat mass were evaluated at 2 time points (mean interval, 16mo). Bone loss was significantly greater in paretic forearms than in nonparetic forearms (p=0.001) and in patients having suffered strokes more recently (p=0.015). We found no difference between paretic and nonparetic femurs. Femoral bone loss was significantly greater in patients using anticoagulants or anticonvulsants (p=0.025) and in those with greater spasticity (p=0.040), regardless of the time since stroke. Our results provide additional evidence that hemiplegic stroke patients have progressive bone loss and that such bone loss is more common in the arms than in the legs. Patients with poststroke hemiplegia should be densitometric monitored mainly in paretic arm and treated for bone loss, with attention to the determinants identified in this study. PMID- 22677200 TI - Digenean communities in the tufted duck [Aythya fuligula (L., 1758)] and greater scaup [A. marila (L., 1761)] wintering in the north-west of Poland. AB - A total of 124 specimens of the tufted duck, Aythya fuligula, and 63 greater scaup, A. marila, were examined for digenean parasites. Both duck species, which overwinter in a coastal lake connected with the southern Baltic (north-west Poland) were found to support Amblosoma exile, Cyathocotyle prussica, Paracoenogonimus ovatus, Australapatemon minor, Cotylurus cornutus, Echinoparyphium recurvatum, Echinostoma revolutum and Notocotylus attenuatus. In addition, the tufted duck hosted Hypoderaeum conoideum, Bilharziella polonica, Neoeucotyle zakharovi, Renicola mediovitellata, Psilochasmus oxyurus, Psilostomum brevicolle and Cryptocotyle concava; Echinostoma nordiana occurred in the greater scaup only. The two duck species differed significantly in the intensity and abundance of their digenean infection. Aythya marila harboured higher intensity levels and a wider assemblage of digeneans than A. fuligula, and this was likely to be due to differences in the pre-wintering exposure of the duck species to infective stages of these freshwater digeneans. Digenean communities in both duck species, strongly dominated by E. recurvatum, were relatively similar in their structure. No significant sex-dependent differences in digenean infections were revealed, except for the infection with N. attenuatus in A. fuligula. Similarly, there were no significant age-dependent differences (adult versus immature birds) in digenean infections, except for that with N. attenuatus in A. fuligula. The structural similarity between digenean communities in the two duck species is most likely an effect of overlapping diets based on freshwater molluscs, components of the digenean transmission pathway to definitive hosts. PMID- 22677199 TI - Transient peripartum osteoporosis of the femoral head in first and third pregnancy. AB - The aim of this article was to present transient peripartum femoral head osteoporosis. This very rare condition occurred twice in our patient-a woman in her 30s. The cases described in the literature were mostly unilateral, with bilateral hip involvement noted much less frequently. In our patient, transient osteoporosis occurred in the third trimester of her first pregnancy in the right hip, her second pregnancy was uncomplicated, and in the third trimester of the patient's third pregnancy, osteoporotic changes were noted in the left hip joint. The patient breastfed her first and third babies only 3 wk each. She breastfed her second baby for 4 mo. The diagnostic workup was based on the clinical examination and radiographic/magnetic resonance imaging, which revealed bone marrow edema, and the dual-energy X-ray absorptiometry scans. The treatment consisted in core decompression of the femoral head (forage), unloading of the hip using crutches as well as administration of calcitonin and calcium supplements. Complete recovery of the femoral heads was achieved. The follow-up time was 7 yr. PMID- 22677201 TI - CD20+ T cell numbers are decreased in untreated HIV-1 patients and recover after HAART. AB - To elucidate if CD20(+) T cells are affected by HIV-1 infection and may have a prognostic value for the course of disease, numbers of CD20(+) T cells were determined in healthy controls, untreated and HAART-treated HIV-1 patients. Coexpression patterns of CD4, CD8, and CD38 were analysed on CD3(+)CD20(+) and CD3(+)CD20(-) T cells. We found a significant decrease of CD20(+) T cell numbers in untreated HIV-1 patients (1.4%) as compared to healthy controls (2.5%) which recovered under HAART (1.9%). Particularly, the CD8(+) T cell compartment was affected revealing significant differences between healthy controls (3.4%) and both treated (1.7%) and untreated (1.1%) patients. CD38 was expressed on a few CD20(+) T cells but preferentially on CD20(-) cells in all three groups. IFN gamma production was measured upon cell activation using PMA alone or in combination with ionomycin in order to assess functional capacities of the cells. PMA alone was much more effective in CD20(+) cells regardless of CD38 coexpression, indicating a supportive role of CD20 but not CD38 in T cell activation. Here we present data showing that CD3(+)CD20(+) T cells are decreased in untreated HIV-1 patients and normal numbers are restored under HAART. Expression of CD20 and CD38 is independently regulated on T cells. Contrary to CD38, CD20 can substitute ionophores for Ca(2+) flux in early T cell activation and also strongly amplify cell stimulation in the presence of Ca(2+) ionophores, indicating that CD20 contributes to T cell activation. PMID- 22677202 TI - Effects of arginine vasopressin on firing activity and thermosensitivity of rat PO/AH area neurons. AB - It is well known that the preoptic-anterior hypothalamus (PO/AH), containing temperature-sensitive and -insensitive neurons plays an important role in precise thermoregulatory responses. Previous in vivo studies suggest that the arginine vasopressin (AVP) is an important endogenous mediator in thermoregulation, since AVP and V(1a) vasopressin receptor antagonist can induce hypothermia and hyperthermia, respectively. In the present study, intracellular electrophysiological activity was recorded from temperature-sensitive and insensitive neurons in rat PO/AH tissue slices, using a whole-cell patch clamp. By monitoring neuron's changes of firing activity and thermosensitivity when perfused with AVP or V(1a) vasopressin receptor antagonist, we found that AVP increased the spontaneous firing rate in 65% of warm-sensitive neurons and decreased it in nearly 50% of cold-sensitive and temperature-insensitive neurons. These changes are due to the AVP enhancing the rise rate of depolarization prepotential in warm-sensitive neurons and reducing it in the other neurons. Moreover, AVP increased the thermosensitivity of warm-sensitive neurons while it decreased thermosensitivity of cold-sensitive and temperature-insensitive neurons. V(1a) vasopressin receptor participated in these responses. Since excited warm-sensitive neurons or inhibited cold-sensitive and temperature insensitive neurons promote heat loss or suppress heat production and retention. These results that AVP excites warm-sensitive neurons and inhibits cold-sensitive and temperature-insensitive neurons suggest a probable mechanism of AVP-induced hypothermia. PMID- 22677203 TI - Cognitive functions of carotid artery stenosis in the aged rat. AB - Carotid artery stenosis appears to be an independent risk factor for cognitive impairment. But the mechanisms of cognitive impairments occurring in patients with asymptomatic carotid stenosis are poorly understood. One important reason is the absence of a good carotid stenosis model. In the present study, after establishing different degrees of carotid stenosis models in aged rats successfully, we investigated their cognitive function. Wistar rat models with carotid artery stenosis were established by ligating the common carotid artery along with various gauges of needle and then removing the needle. The cognitive performance was assessed using Morris water maze (MWM) task. Cholinergic markers like acetylcholine (ACh) were evaluated in hippocampus. Neuronal damage was also studied through morphological changes. Severe carotid stenosis led to impairment in learning ability and memory retrieval, accompanied with a decrease in ACh level and morphological damage in hippocampus. Moderate carotid stenosis rats had a partial cognitive impairment, but there were no changes in ACh level and morphological damage in hippocampus. Meanwhile, mild carotid stenosis rats had no cognitive impairment compared to sham-operated rats. The results of this study suggest that different degrees of carotid stenosis induce different cognitive changes in aged rats. PMID- 22677204 TI - The reduced glutathione and S-nitrosothiols levels in acute phase of experimental demyelination--pathophysiological approach and possible clinical relevancy. AB - Multiple sclerosis (MS) is characterized by inflammatory process associated with nitric oxide (NO) and the related species production in CNS, which can nitrosylate protein thiols and modulate their structure and functions, also reducing the CNS content of redox active compounds, such as glutathione (GSH). We have evaluated the relationships between S-nitrosothiols (RSNO) and GSH in the experimental model of MS - experimental autoimmune encephalomyelitis (EAE), during the treatment with inducible NO synthase inhibitor - aminoguanidine (AG) and thiol donor molecule - N-acetyl-L-cysteine (NAC). MATERIAL AND METHODS: EAE was induced by myelin basic protein, dissolved in phosphate-buffered saline (PBS), emulsified in the complete Freund's adjuvant (CFA) followed by injections of Pertussis toxin. Animals assigned to the control (PBS), EAE, CFA, EAE+AG, AG, EAE+NAC and NAC groups were scored daily for the clinical signs of EAE. RSNO and GSH were evaluated in whole encephalitic mass and cerebellum. RESULTS: RSNO concentration was increased in EAE-untreated animals compared to the AG and NAC treated EAE animals (p<0.05). Also, during the treatment with AG and NAC, GSH concentration was increased compared to the untreated animals (p<0.05). The EAE clinical signs were reduced in EAE-treated animals compared to the other groups (p<0.05). CONCLUSION: The findings of our work suggest a potential role of RSNO and GSH in early clinical presentation of experimental MS, that might be also useful as predictive parameters for MS treatment directed to increased GSH and thiol pool in CNS. PMID- 22677205 TI - Transient mGlu5R inhibition enhances the survival of granule cell precursors in the neonatal cerebellum. AB - The generation of the most abundant neurons of the cerebellum, the granule cells, relies on a balance between clonal expansion and apoptosis during the first 10 days after birth in the external germinal layer (EGL). The amino acid glutamate controls such critical phases of cell development in other systems through specific receptors such as metabotropic glutamate receptor 5 (mGlu(5)R). However, the function of mGlu(5)Rs on the proliferation and survival of granule cell precursors (GCPs) remains elusive. We found mGlu(5)R mRNA transcripts in EGL using RT-PCR and observed mGlu(5)R-mediated Ca(2+) responses in GCPs in acute slices as early as postnatal day (P) 2-3. Using in vivo injections of the selective non-competitive mGlu(5)R antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP) in P7-P9 mice, we found a 20% increase in the number of proliferative GCPs labeled at P7 with the S-phase marker bromodeoxyuridine (BrdU), but no increase in cell proliferation examined 2h following a BrdU injection. Furthermore, similar treatments led to a significant 70% decrease in the number of apoptotic GCPs in the EGL as determined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. In contrast, in vivo treatment with the mGlu(5)R agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG) resulted in a ~60% increase in the number of TUNEL-labeled GCPs compared to control. These findings identify a unique role for glutamate acting at mGlu(5)Rs as a functional switch regulating GCP survival in the EGL, thus controlling the total number of cerebellar granule cells produced. PMID- 22677206 TI - Polyclonal rabbit antithymocyte globulin induces apoptosis and has cytotoxic effects on human leukemic cells. AB - The possibility of antileukemic activity of antithymocyte globulin (ATG) was investigated in 8 human leukemic cell lines and primary leukemic cells from 15 leukemia patients. The study demonstrated that ATG induced apoptosis and reduced proliferation in both cell lines and primary leukemic cells, particularly in lymphatic origin cells, indicating that ATG has broad-spectrum antileukemic activity, especially for cells of lymphatic origin. BACKGROUND: Polyclonal ATGs are currently used to prevent graft-versus-host disease in allogeneic stem cell transplantation patients and to treat patients with severe aplastic anemia. It contains antibodies against antigens expressed on various hematopoietic cells, we hypothesized that it induces cell death not only in healthy cells but also in malignant hematopoietic cells. MATERIALS AND METHODS: In this study, several human leukemic cell lines and primary leukemic cells from 15 patients with leukemia were used to investigate the ability of polyclonal ATGs to induce apoptosis and proliferation. RESULTS: Polyclonal ATGs induced cell apoptosis in primary leukemic cells and in cell lines in a dose-dependent manner, and induced apoptosis in different populations through a variety of targets. Cell proliferation was significantly reduced in the presence of polyclonal ATGs; it arrested cells in the G0-G1 phase by cell cycle analysis. Treatment with polyclonal ATGs plus complement increased cytolysis of the leukemic cells; complement augments polyclonal ATG-induced leukemic cell death. CONCLUSION: These data show that polyclonal ATG has broad-spectrum antileukemic activity, especially for cells of lymphatic origin, as it induced cell death through a variety of targets. This study provides an experimental basis for the application of polyclonal ATGs in allogeneic hematopoietic stem cell transplantation and in patients with lymphatic leukemia. PMID- 22677207 TI - Long term estradiol-17beta administration changes population of the dorsal root ganglia neurons innervating the ovary in the sexually mature gilts. AB - The influence of estradiol-17beta (E2) overdose on the number and distribution of neurons in the dorsal root ganglia (DRGs) supplying the ovary of adult pigs was investigated. The numbers of ovarian substance P (SP)-, calcitonin gene-related peptide (CGRP)-, galanin (GAL)-, pituitary adenylate cyclase-activating polypeptide (PACAP)-, neuronal isoform of nitric oxide synthase (nNOS)- and estrogen receptors (ERs)-immunoreactive perikarya were also determined. On day 3 of the estrous cycle, the ovaries of both the control and experimental gilts were injected with retrograde tracer Fast Blue. From day 4 of the estrous cycle to the expected day 20 of the second studied cycle, the experimental gilts were injected with E2, while the control gilts received oil. The DRGs Th16-L5 were then collected and processed for double-labelling immunofluorescence. Injections of E2 increased the E2 level in the peripheral blood ~4-5-fold and reduced the following in the DRGs: the total number of Fast Blue-positive perikarya, the number of large perikarya, the population of perikarya in the L2 and L3 ganglia, the numbers of SP- and/or CGRP-, PACAP-, nNOS-immunoreactive perikarya and the number of large perikarya expressing ERs subtype alpha and beta. These results show that long-term E2 treatment of adult gilts affects both the spatial and neurochemical organization pattern of ovary sensory innervation. Our findings suggest that elevated E2 levels occurring during pathological states may regulate the transmission of sensory modalities from the ovary to the spinal cord. PMID- 22677208 TI - The role of painful events and pain perception in blood-injection-injury fears. AB - BACKGROUND AND OBJECTIVES: Research suggests that blood, injection, and injury (BII) fears are related to painful experiences; however the role of frequency, intensity, and perceived ability to handle such events remains unknown. The aim of this study was to examine the relationship between BII fears and the frequency and intensity of prior painful experiences with blood, injuries, and injections. The relation of BII fears with self-reported tolerance and avoidance of physical discomfort and pain was also examined. METHODS: In the context of an undergraduate student survey, 392 participants completed questions about whether they were fearful of blood, injection, and injuries. They also completed questions about experiences with blood and injuries, as well as injections, including pain intensity, frequency of painful experiences, perceived ability to tolerate physical discomfort and pain (pain perception), and avoidance of physical discomfort. RESULTS: Findings indicated that only pain intensity, but not frequency of painful experiences with blood, injuries, and injections, was related to BII fears. Furthermore, there was a significant association between BII fears and pain perception, such that higher levels of discomfort intolerance were related to greater odds of endorsing BII fears. CONCLUSIONS: These findings provide preliminary evidence that BII fears are associated with experiences with injections of high pain intensity. Individuals with a lower perceived ability to handle physical pain and discomfort are more likely to endorse BII fears. Clinical considerations and future directions are discussed. PMID- 22677209 TI - Vitamin D and primary hyperparathyroidism (PHPT). AB - Vitamin D deficiency and primary hyperparathyroidism (PHPT) are two common conditions, especially in postmenopausal women. Vitamin D deficiency is said to be even more frequent in PHPT patients than in the general population due to an accelerated conversion of 25-hydroxy vitamin D (25OHD) into calcitriol or 24 hydroxylated compounds. Although several studies have reported worsening of PHPT phenotype (larger tumours, higher parathyroid hormone [PTH] levels, more severe bone disease) when vitamin D deficiency coexists whereas vitamin D supplementation in PHPT patients with a serum calcium level less than 3 mmol/L has been shown to be safe (no increase in serum or urinary calcium) and to decrease serum PTH concentration, many physicians are afraid to give vitamin D to already hypercalcemic PHPT patients. It is possible that, in some patients, a persistent vitamin D deficiency induces, in the long-term, an autonomous secretion of PTH (i.e. tertiary hyperparathyroidism). The mechanism by which this could occur is unclear however. Finally, as many, otherwise normal, subjects with vitamin D insufficiency may have an increased serum PTH level we believe that those with vitamin D insufficiency should be excluded from a reference population for serum PTH levels. By doing that, we found that the upper normal limit for serum PTH was 25-30% lower than in the whole population. PMID- 22677210 TI - Bert Vallee, an extraordinary scientist. PMID- 22677211 TI - Testing social acoustic memory in rats: effects of stimulus configuration and long-term memory on the induction of social approach behavior by appetitive 50 kHz ultrasonic vocalizations. AB - Rats emit distinct types of ultrasonic vocalizations (USVs), which serve as situation-dependent affective signals. In appetitive situations, such as rough and-tumble-play, high-frequency 50-kHz USVs occur, whereas low-frequency 22-kHz USVs can be observed in aversive situations, such as social defeat. USVs serve distinct communicative functions and induce call-specific behavioral responses in the receiver. While aversive 22-kHz USVs serve as alarm calls and induce behavioral inhibition, appetitive 50-kHz USVs have a pro-social communicative function and elicit social approach behavior, supporting the notion that they serve as social contact calls to (re)establish or maintain contact among conspecifics. The aim of the present study was to use the rat's ability to communicate in the ultrasonic range via high-frequency 50-kHz USVs in order to develop a test for social acoustic memory in rats with relevance for human verbal memory. Verbal learning and memory is among the seven cognitive domains identified as commonly deficient in human schizophrenia patients, but particularly difficult to model. We therefore tested whether the induction of social approach behavior by playback of appetitive 50-kHz USVs is dependent on (1) acoustic stimulus configuration and (2) social long-term memory, and whether (3) social long-term memory effects can be blocked by the administration of scopolamine, a muscarinic acetylcholine antagonist producing amnesia. Results show that social approach behavior in response to playback of natural 50-kHz USVs depends on acoustic stimulus configuration and occurs only when sound energy is concentrated to a critical frequency band in the ultrasonic range. Social approach behavior was detected during the first exposure to playback of 50-kHz USVs, whereas no such response was observed during the second exposure 1week later, indicating a stable memory trace. In contrast, when memory formation was blocked by i.p. administration of scopolamine (0.5mg/kg or 1.5mg/kg) immediately after the first exposure, rats displayed social approach behavior during the second exposure as well. Induction of social approach behavior in response to repeated playback of natural 50-kHz USVs may therefore provide a new and rather unique approach for testing social acoustic memory in rats with relevance to human verbal memory. PMID- 22677213 TI - Honey dressing use for the management of split thickness skin graft donor sites: a technical note. PMID- 22677214 TI - Functional long-term results after the harvest of vascularised iliac bone grafts bicortically with the anterior superior iliac spine included. AB - The aim of this study was to evaluate the postoperative morbidity at the donor site and the long-term outcome after the harvest of bicortical iliac bone grafts, including the iliac crest and the anterior superior iliac spine (ASIS), by using a confirmed score. We retrospectively examined 54 consecutive patients who had had vascularised iliac bone grafts harvested to reconstruct different parts of the mandible. We used the Harris Hip Score to evaluate objectively the long-term postoperative morbidity at the donor site. Of 54 patients, 20 were female (37%) and 34 male (63%), with a mean age of 49 years (range 12-81). The causes of the bony defects were malignancy (n=37, 69%), benign tumours (n=7, 13%), osteomyelitis (n=9, 17%), and atrophy of the alveolar ridge (n=1, 2%). All transplants healed adequately. A total of 38/52 patients (73%) had a score of more than 80 points, which defines clinical success. Vascularised iliac bone grafts offer excellent bony dimensions with optimal shape to be used for reconstruction of different parts of the mandible. They can be harvested bicortically, including the iliac crest and the ASIS, with acceptable morbidity at the donor site. The Harris Hip Score is an appropriate tool for the evaluation of long-term impairment at the donor site after the harvest of vascularised iliac bone grafts, and it could be used to compare the results of different studies. PMID- 22677215 TI - Proforma for maxillofacial trauma. AB - Over a three-year period we devised, developed, and implemented a simple proforma, validated by a previous audit, to improve the accuracy of data collected on maxillofacial trauma. It covers both sides of an A4 sheet and functions as an aide-memoire for junior staff and prompts the comprehensive recording of all necessary medicolegal details should further documentation be required by the police, judiciary, or compensatory body. PMID- 22677216 TI - Elderly patients with maxillofacial trauma: the effect of an ageing population on a maxillofacial unit's workload. AB - The purpose of this study was to identify the aetiology and management of facial fractures in patients over 60 years old and to identify potential trends in caseload to assist with planning of resources for maxillofacial services in the coming decades. We made a prospective study over 2 years (2009-2010), during which all injured patients referred to the oral and maxillofacial surgery unit at The Canberra Hospital, Australia were recruited. The patients were classified into two groups: less than 60 years old (younger group); or 60 years old or more (older group). Factors studied included sex, age, aetiology, site of fractures, severity scored using the Maxillofacial Injury Severity Score (MFISS), and management. Based on current trends, the expected workload was extrapolated. A total of 470 patients were recruited (younger: n=430 and older: n=40). Falls were the most common cause of fracture in the older group (85%) and the zygoma (40%) was the bone most commonly fractured. The mean (SD) MFISS for the older group was 3.8 (2.2) (17% of these maxillofacial injuries were operated on) and 6.0 (5.0) for the younger group (72% of these were operated on). In Australia, population trends suggest that older people as a proportion of the total population will rise from about 20% of 22 million to 26% of 30 million by 2034. As the older group increases there will be a corresponding increase in the number of older people who present with trauma to maxillofacial units. The overall maxillofacial surgical workload will probably not increase much because the injuries tend to be less severe and are less likely to require operation. PMID- 22677217 TI - Nursing students' perceptions towards cancer and caring for cancer patients in Turkey. AB - PURPOSE: This descriptive study investigated nursing students' perceptions about cancer and their experiences of caring for cancer patients. METHODS: The study was conducted in a school of nursing in Ankara, Turkey. In the first instance, a self-report questionnaire on socio-demographic characteristics, experience of caring for cancer patients, and a 22 item Likert scale questionnaire eliciting students' perceptions about cancer was administered (n = 167). In the next stage, 24 third and fourth year students were invited to attend two focus groups to explore their experiences of caring for cancer patients. RESULTS: Less than half of the students in the study had prior experience of caring for cancer patients but the majority displayed positive perceptions towards cancer. The main themes emerging from the study were: hardship, uncertainty, fear, hope, and the association of cancer with death. Difficulties encountered included communication problems, helplessness and fear of doing wrong. Preceptors, nurses and peers were the most common sources of support. Students suggested the need for orientation programs, introduction by the facilitator to the oncology team, organizing meetings to share experiences, extending the duration of practice placements and organizing motivating activities. CONCLUSIONS: Educational programs and supportive strategies may alleviate fears and promote a more positive image of cancer amongst nursing students. PMID- 22677218 TI - Relationships among pain, depressed mood, and global status in fibromyalgia patients: post hoc analyses of a randomized, placebo-controlled trial of milnacipran. AB - BACKGROUND: Patients with fibromyalgia often experience depressive symptoms in addition to chronic pain and other characteristic symptoms associated with this disorder. OBJECTIVE: To examine the relationships among pain, depressive symptoms, and global status in a clinical trial of milnacipran for fibromyalgia. METHODS: Data from a randomized, double-blind study (milnacipran 100 mg/d, n = 516; placebo, n = 509) were analyzed. Treatment outcomes included quantitative changes in pain and Beck depression inventory (BDI) scores, mean Patient Global Impression of Change (PGIC) scores, and three responder endpoints: patients with >=30% pain improvement, PGIC score <=2, and patients meeting both pain and PGIC responder criteria (2-measure composite responders). Correlations and path analyses were conducted to evaluate relationships among improvements in depressive symptoms, pain, and PGIC. RESULTS: Patients receiving milnacipran had greater decreases in mean pain scores, lower mean PGIC endpoint scores, and higher responder rates regardless of baseline severity of depressive symptoms. The highest responder rates were found in patients with greater than four-point improvement in BDI scores (milnacipran vs. placebo: pain, 57.5% vs. 39.0%; PGIC, 60.1% vs. 38.2%; 2-measure composite, 49.0% vs. 27.9%; all p < 0.01), although significant differences between treatment groups were also found in patients with no improvement or worsening of depressive symptoms. Correlations between changes in BDI and changes in pain or PGIC were low (r <= 0.3). Path analyses indicated 87.2% of pain reduction to be a direct effect of milnacipran treatment. CONCLUSION: Symptom improvements with milnacipran were only weakly associated with baseline depressive symptoms and were largely independent of improvements in depressive symptomatology. PMID- 22677219 TI - Cotard's syndrome with catatonia: a case presentation and discussion. PMID- 22677220 TI - Efficacy and safety of emergency non-invasive pelvic ring stabilisation. AB - BACKGROUND: Urgent non-invasive pelvic ring stabilisation (pelvic binding, PB) in shocked patients is recommended by state and institutional guidelines regardless of the fracture pattern. The purpose of this study was to determine the adherence to the guidelines, efficacy of the technique and identification of potential adverse effects associated with PB. PATIENTS AND METHODS: A 41-month retrospective analysis of the prospective pelvic fracture database was undertaken at a level 1 trauma centre. High-energy pelvic fractures were included in the analysis with exclusion of the A type injuries (AO/OTA classification) and patients who were dead on arrival. Collected data included patient demographics, injury severity score, fracture classification, application and timing of PB, associated injuries, physiological parameters, resuscitation fluids and outcomes. Pre and post-PB radiographs were reviewed. The potential effects of the PB on soft tissue (femoral vessel, bladder and rectal injury) complications were assessed by independent experts. RESULTS: 115 patients with high-energy B and C type pelvic ring injuries were included. Thirty-six (31%) patients presented in haemorrhagic shock on arrival. A total of 43 pelvic bindings were performed, 18 of them on shocked patients. The adherence to the guidelines was 50% (18/36) overall. Analysing fracture types of shocked patients the adherence was: B1 80%, B2 20%, B3 20%, C1 66%, C2 86%, C3 33%. The alignment of the pelvis was improved or perfect on post-PB radiographs in 68% and had not changed in 21%. In some cases of B2 and B3 type injuries the PB increased the deformity after application (11%). There were 10 deaths (8.7%) in the study group, with 4 deaths attributed to acute pelvic bleeding. Two of these had PB applied and two were identified as potential for improvement. One femoral artery injury, four bladder injuries and three rectum injuries were identified in patients who had PB applied. Association between the PB and these injuries is unlikely. CONCLUSION: The adherence to the guidelines should be improved with further education and system development. The good effect of the technique was evident on radiographs. Although in some lateral compression fracture patterns the deformity increased, no hazards were associated with the use of PB. PMID- 22677221 TI - Early coagulopathy of major burns. AB - INTRODUCTION AND AIMS: The pathophysiology and time-course of coagulopathy post major burns are inadequately understood. The aims of this study were to review the incidence of acute coagulopathy post major burns, potential contributing factors associated with this coagulopathy and outcome of patients who developed early coagulopathy. METHODS: A retrospective review of all patients with major burns (>=20% total body surface area (TBSA)) presenting to a tertiary burns referral centre was conducted. Data on demographic, injury characteristics and fluid resuscitation practices were recorded and tested for association with coagulopathy (INR>1.5 or aPTT>60 s) at hospital presentation and within 24 h of burns injury. Mortality, intensive care unit (ICU) admission, mechanical ventilation and blood and blood product usage were primary endpoints. RESULTS: There were 99 patients who met the inclusion criteria with 36 (16) %TBSA burns. Coagulopathy was present in only three patients on presentation, but 37 (37%) patients developed early onset (within 24 h of injury) coagulopathy. Early onset coagulopathy was independently associated with %TBSA burnt (p<0.001) and volume of fluid administered (p=0.005). Early onset coagulopathy was associated with higher volumes of blood and blood product administration, ICU admission and prolonged mechanical ventilation. CONCLUSIONS: Post major burns, a very low proportion of patients presented with coagulopathy, but a substantial proportion of patients developed coagulopathy within 24 h. This and the association of coagulopathy with the volume of fluid resuscitation suggest dilution as a major cause of the early coagulopathy of major burns. PMID- 22677223 TI - The NHS is right to fund homoeopathy. PMID- 22677222 TI - Spatio-temporal trends and risk factors for Trichinella species infection in wild boar (Sus scrofa) populations of central Spain: a long-term study. AB - In south-central Spain, the harvest of Eurasian wild boar (Sus scrofa) has increased significantly during recent decades in association with more intensive management actions to increase hunting yields and with consequent effects on the health status of the wild boar populations. We investigated the spatio-temporal trends and the risk factors related to the prevalence of Trichinella spp. in wild boar in order to obtain the annual probability of occurrence for these parasites in the Ciudad Real province of south-central Spain. Based on muscle samples collected during the hunting seasons from 1998/1999 to 2009/2010, the mean prevalence for Trichinella spp. in 95,070 wild boar was 0.2% (95% confidence interval 0.17-0.23). A subsample of 1,432 wild boar was also tested by ELISA. No correlation was observed between the prevalence of infection detected by serology and by the artificial digestion of muscle. The presence of Trichinella infections in wild boar showed a decreasing trend during the study period and was negatively related with fenced wild boar populations. The predicted 'favourability' for Trichinella infections disappeared almost completely after the 2006/2007 hunting season. Risk maps based on biogeographical tools showed, however, that most hunting estates presented favourable risk factors for these parasites during at least one of the hunting seasons studied. PMID- 22677224 TI - Improved diagnosis of spring viremia of carp by nested reverse-transcription PCR: development of a chimeric positive control for prevention of false-positive diagnosis. AB - Polymerase chain reaction (PCR) assays allow for the rapid and accurate detection of infectious agents through identification of nucleic acid sequences. However, contamination of samples with positive DNA can lead to false-positive results. In this study, positive control plasmids were developed to minimize false-positive reactions due to PCR contamination during detection of SVCV by semi-nested reverse-transcription PCR. An ampicillin resistance gene was truncated by PCR amplification, and the fragments were inserted into pGEM-T Easy vectors; the resulting plasmids were named SVCV chimeric plasmid-1 and chimeric plasmid-2, respectively. Through a series of semi-nested PCRs, the use of SVCV chimeric plasmids-1 and -2 was shown to ensure correct diagnoses, free from PCR contamination. The results of this study show that PCR positive controls can be created without use of viral nucleic acids or pathogen-infected tissues. The technique can be applied to quarantined material and can be used to detect other pathogens. PMID- 22677225 TI - Improved sensitivity of influenza A antigen detection using a combined NP, M, and NS1 sandwich ELISA. AB - A new modified triple-antigen detection test was developed for the direct detection of the influenza A virus. The nucleoprotein (NP), matrix (M), and non structural (NS1) proteins were used as target antigens because they are abundant in infected cells. Monoclonal antibodies specific to the NP, M, and NS1 proteins were generated. The antibody pairs were selected and evaluated for their reactivity individually and in combination in the triple-antigen detection using sandwich ELISA. Triple-antigen detection demonstrated a higher sensitivity than individual antigen detection when tested with both the H1N1 and H3N2 influenza A viruses. This was illustrated by the 4-fold lower limit of detection of the triple-antigen test than the individual antigen detection test. The findings demonstrated that the sensitivity of influenza A antigen detection was improved with the triple-antigen detection system as compared to individual antigen detection. Therefore, this technique could be a useful tool for the direct detection of cell-associated influenza A antigen. Furthermore, it could provide a basis for the development of a rapid triple-antigen test for influenza A diagnosis. PMID- 22677226 TI - Reprint of: Effects of BDNF polymorphisms on brain function and behavior in health and disease. AB - Brain-derived neurotrophic factor (BDNF), the most abundant neurotrophin in the brain, serves an important role during brain development and in synaptic plasticity. Given its pleiotropic effects in the central nervous system, BDNF has been implicated in cognitive function and personality development as well as the pathogenesis of various psychiatric disorders. Thus, BDNF is considered an attractive candidate gene for the study of healthy and diseased brain function and behaviors. Over the past decade, many studies have tested BDNF genetic association, particularly its functional Val66Met polymorphism, with psychiatric diseases, personality disorders, and cognitive function. Although many reports indicated a possible role for BDNF genetic effects in mental problems or brain function, other reports were unable to replicate the findings. The conflicting results in BDNF genetic studies may result from confounding factors such as age, gender, other environmental factors, sample size, ethnicity and phenotype assessment. Future studies with more homogenous populations, well-controlled confounding factors, and well-defined phenotypes are needed to clarify the BDNF genetic effects on mental diseases and human behaviors. PMID- 22677227 TI - Sebaceoma of the auricle. AB - OBJECTIVE: To report a case of sebaceoma of the auricle, and to discuss the differential diagnosis, histopathological features, surgical management and genetic associations of this entity. METHODS: Case report and review of the medical literature. RESULTS: A 79-year-old man presented with a slowly growing lesion of his auricle. Excision of the mass and histopathological review revealed a benign, basaloid, adnexal neoplasm consistent with sebaceoma. Due to its association with Muir-Torre syndrome and increased risk of visceral malignancy, the patient was followed closely for signs of malignancy. At 36 months post excision, there were no signs of recurrence; thereafter, the patient continued to receive routine cancer surveillance follow up. CONCLUSION: Sebaceoma is a rarely encountered, benign, adnexal neoplasm which can occur in the head and neck. The treatment is surgical excision, and recurrence is rare. Sebaceoma can occur as part of Muir-Torre syndrome, and in these patients there is an increased risk of other sebaceous lesions and visceral malignancy; thus, genetic testing and surveillance should be strongly considered. PMID- 22677228 TI - Bilateral internal thoracic artery grafting is associated with significantly improved long-term survival, even among diabetic patients. AB - BACKGROUND: This study examines if bilateral internal thoracic artery (BITA) grafting provides improved outcomes compared with single internal thoracic artery (SITA) grafting, in the modern era, in which diabetes mellitus and obesity are more prevalent. METHODS: The Society of Thoracic Surgeons database at a single large academic center was reviewed for all consecutive isolated coronary artery bypass grafting patients with two or more distal anastomoses from January 1, 2002, through December 31, 2010. Propensity-adjusted logistic and Cox regression models were used to estimate the effect of BITA on short-term outcomes and long term survival for diabetic and nondiabetic patients. RESULTS: A total of 3,527 coronary artery bypass grafting operations (812 BITA, 2,715 SITA) were performed. Fewer BITA than SITA patients had diabetes (28.6% vs 44.7% p<0.001). There was no significant difference in 30-day rates of death, stroke, or myocardial infarction between nondiabetic patients who had BITA vs SITA, or between diabetic patients who had BITA vs SITA. BITA grafting conferred a 35% reduction (95% confidence interval, 12% to 52%, p=0.006) in the long-term hazard of death equally for nondiabetic and diabetic patients (p=0.93). Deep sternal wound infection was more common among diabetic than among nondiabetic patients (1.5% vs 0.7%), but was similar within nondiabetic (1.0% vs 0.6%) and diabetic patients (1.7% vs 1.5%) who had BITA vs SITA. Overall, BITA and SITA patients had similar rates of deep sternal wound infection (1.2% vs 1.0%). CONCLUSIONS: BITA grafting confers a long term survival advantage and should be performed whenever suitable coronary anatomy exists and patient risk factors allow an acceptable risk of deep sternal wound infection. PMID- 22677230 TI - miRNA mediated up-regulation of cochaperone p23 acts as an anti-apoptotic factor in childhood acute lymphoblastic leukemia. AB - p23 is a heat shock protein 90 (Hsp90) cochaperone that plays a significant role in estrogen receptor (ER) alpha signal transduction and telomerase activity; it is up-regulated in several cancers. Recent studies have found that high level of p23 may promote tumor progression and poor prognosis in breast cancer patients. p23 was found to be overexpressed in our previous microarray assay of 100 childhood acute lymphoblastic leukemia (ALL) bone marrow (BM) samples. In the present study, we verified the upregulation of p23 in clinical ALL samples, and identified p23 to be an anti-apoptotic factor in the process of chemotherapy. We also found that p23 was regulated by hsa-miR-101 which was down-regulated in childhood ALL cases. Altogether these data demonstrate that the misregulation of hsa-miR-101 contributes partly to the overexpression of p23 in childhood ALL. As an anti-apoptotic factor, p23 is able to be a potential target for anti-leukemic therapy. PMID- 22677229 TI - Reduced intensity allogeneic hematopoietic stem cell transplantation for MDS using tacrolimus/sirolimus-based GVHD prophylaxis. AB - We report a consecutive series of 59 patients with MDS who underwent reduced intensity hematopoietic stem cell transplantation (RI-HSCT) with fludarabine/melphalan conditioning and tacrolimus/sirolimus-based GVHD prophylaxis. Two-year OS, EFS, and relapse incidences were 75.1%, 65.2%, and 20.9%, respectively. The cumulative incidence of non-relapse mortality at 100 days, 1 year, and 2 years was 3.4%, 8.5%, and 10.5%, respectively. The incidence of grade II-IV acute GVHD was 35.4%; grade III-IV was 18.6%. Forty of 55 evaluable patients developed chronic GVHD; of these 35 were extensive grade. This RI-HSCT protocol produces encouraging outcomes in MDS patients, and tacrolimus/sirolimus-based GVHD prophylaxis may contribute to that promising result. PMID- 22677231 TI - A randomized controlled trial of internet-based therapy in depression. AB - Depression is among the most prevalent disorders worldwide. In view of numerous treatment barriers, internet-based interventions are increasingly adopted to "treat the untreated". The present trial (registered as NCT01401296) was conducted over the internet and aimed to assess the efficacy of an online self help program for depression (Deprexis). In random order, participants with elevated depression symptoms received program access or were allocated to a wait list control condition. After eight weeks, participants were invited to take part in an online re-assessment. To compensate for common problems of online studies, such as low completion rates and unclear diagnostic status, reminders and incentives were used, and clinical diagnoses were externally confirmed in a subgroup of 29% of participants. Relative to the wait-list group, program users experienced significant symptom decline on the Beck Depression Inventory (BDI; primary outcome), the Dysfunctional Attitudes Scale (DAS), the Quality of Life scale (WHOQOL-BREF) and the Rosenberg Self-Esteem Scale (RSE). Compared to wait list participants, symptom decline was especially pronounced among those with moderate symptoms at baseline as well as those not currently consulting a therapist. Completion (82%) and re-test reliability of the instruments (r = .72 .87) were good. The results of this trial suggest that online treatment can be beneficial for people with depression, particularly for those with moderate symptoms. PMID- 22677232 TI - Do aspirin and non-steroidal anti-inflammatory drugs increase the risk of post sphincterotomy hemorrhage--a case-control study. AB - BACKGROUND AND OBJECTIVE: Non-steroidal anti-inflammatory drugs (NSAIDs) and aspirin have antiaggregant properties and patients with pancreaticobiliary disease commonly use these drugs. We prospectively investigated whether aspirin and NSAIDs are associated with endoscopic sphincterotomy related hemorrhage. METHODS: Three hundred and eight patients who underwent sphincterotomy were sequentially recruited into this prospective case-control study. Pre-endoscopic assessment included a complete blood count, coagulation studies and a detailed drug history after sphincterotomy patients were followed up for bleeding. Cases and controls were compared for patient and procedure-related risk factors of post endoscopic sphincterotomy bleeding. RESULTS: Hemorrhage occurred in 74 (24%) patients. Eight (2.6%) were clinically significant and five (1.6%) were severe. Amongst cases with hemorrhage, 17.6% were on NSAIDs and 14.9% on aspirin; 27.4% of controls took NSAIDs, and 9.8% aspirin (P>0.05). Aspirin use in patients with significant (12.5%) or severe hemorrhage (20%) was not different from the controls (P>0.05) and none of them had NSAIDs prior to sphincterotomy. Based on univariate analysis, coagulopathy and comorbidity were risk factors for significant post-sphincterotomy hemorrhage and coagulopathy was the only independent parameter (odds ratio=22.72, 95% CI [4.25; 125]). CONCLUSION: Aspirin and NSAIDs do not increase the risk of post-sphincterotomy hemorrhage and they can be safely used before the procedure. PMID- 22677233 TI - A Danish reference chart for assessment of psychomotor development based on the Ages & Stages Questionnaire. AB - INTRODUCTION: The aim of this study was to obtain Ages and Stages Questionnaire (ASQ) scores from the background population so that these may be used as a reference group to extremely preterm children at nine and 18 months of corrected age. MATERIAL AND METHODS: A total of 298 children were randomly chosen among the Danish population in three different groups: 9-, 18- and 21 month-old children. The parents received the 10-month ASQ when their child had reached a corrected age of nine months and the 24-month ASQ questionnaire when their child had reached the corrected age of 18 or 21 months. RESULTS: The total scores were normally distributed in both groups. There was a highly significant (p < 0.001) linear regression between ASQ total score and adjusted age for both the 10- and the 24-month ASQ. CONCLUSION: The results of the study show that the overall development can be assessed when the child is scored with an ASQ intended for older children. Screening for developmental delay in children in the age range of 8-10 months or 18-22 can be quickly assessed by reference to a chart. The chart can also be used as a reference when monitoring the quality in neonatal services by the developmental outcome and this ensures that children are classified according to Danish standards. PMID- 22677234 TI - Poor agreement between data from the National Patient Registry and the Danish Patient Insurance Association. AB - INTRODUCTION: Septic arthritis after knee arthroscopy requires in-patient treatment and should thus be reported to the National Patient Registry (NPR). It also meets the requirements for financial compensation if claimed to the Danish Patient Insurance Association (DPIA). The aim of this study was to assess data from the two independent data sources, the NPR and DPIA, with a view to comparing the registration of septic arthritis after knee arthroscopy. MATERIAL AND METHODS: This was a retrospective study assessing two three-year periods. From the NPR, we initially received all contacts coded as arthroscopic knee surgery. A second NPR query was made for patients found in the first query who had had a hospital contact within 30 days postoperatively with codes indicating septic arthritis (450 patients). Correspondingly, the DPIA files of patients claiming an infection following knee arthroscopy were searched to identify those (157 patients) with post-arthroscopic septic arthritis. RESULTS: We found poor agreement between the 450 patients in the second NPR data extraction and the 157 verified patients from the DPIA. Only 105 patients from DPIA were found in the NPR, while 52 patients in the DPIA were not returned as part of the second NPR data extraction. CONCLUSION: Coding of infections after arthroscopy in the NPR is inconsistent and incomplete. An underreporting of septic arthritis to the DPIA might exist. PMID- 22677235 TI - Less tachycardia during transnasal versus conventional gastroscopy. AB - INTRODUCTION: Transnasal endoscopy is well tolerated, but physiological benefits compared with conventional gastroscopy have not been studied in detail. The aims of this randomised study were to evaluate cardiopulmonary features, patient tolerance, and the endoscopist's evaluation of transnasal versus conventional endoscopy. MATERIAL AND METHODS: Patients were randomized to either a conventionally sized transoral (50 patients) or to a transnasal endoscopy (48 patients). Pulse rate and oxygen saturation were registered as well as the patient's tolerance and the endoscopist's evaluation of the procedure. RESULTS: The success rate for transnasal gastroscopy was 77%, mainly because of nasal stenosis. The per- and post-endoscopy pulse rates of the conventional group were elevated compared with those of the transnasal group (p = 0.04 and p = 0.02). Procedural discomfort in the two groups was similar, but significantly fewer transnasal patients reported gagging (p < 0.01). The endoscopists evaluated the technical features as good even if they did not reach those of conventional gastroscopy (p < 0.05). CONCLUSION: In this study, transnasal gastroscopy was technically inferior to conventional gastroscopy. There was no benefit in terms of patient comfort, except for less gagging. A lower stress response was indicated by significantly lower pulse rates during transnasal than during conventional gastroscopy, but the clinical relevance of this finding needs to be further investigated. PMID- 22677236 TI - Low morbidity after palliation of obstructing gastro-oesophageal adenocarcinoma to restore swallowing function. AB - INTRODUCTION: This study describes the procedure-related complications and survival after deployment of self-expanding metal stents (SEMS) or use of argon plasma coagulation (APC) in patients with obstructing gastro-oesophageal junction (GEJ) adenocarcinoma. MATERIAL AND METHODS: During an 8-year period, 312 patients with non-resectable, obstructing adenocarcinoma at the GEJ were treated with SEMS and/or APC and thereafter followed with endoscopies. RESULTS: A total of 707 procedures (246 SEMS procedures and 461 ablations) were performed. No patients died in relation to the procedures. Minor bleeding during APC was seen in 20 patients. Early complications to SEMS were migration and misplacement. A single perforation with the guide-wire was seen. Late complications were tumour overgrowth and food impaction. A single treatment with SEMS or APC was performed in 115 (37%) and 49(16%) patients, respectively. SEMS replacement was necessary in 17 (5%) patients. Repeated APC treatments were necessary in 57 (18%) patients. The median time of survival in patients treated with SEMS, APC or both procedures was 134 days, 114 days and 215 days (p = 0.004), respectively. The survival in patients palliated with SEMS and/or APC alone was significantly lower compared to those who were palliated with SEMS and/or APC in combination with chemoradiotherapy. The median time of survival was 120 days in SEMS and 203 days in APC patients (p = 0.05). CONCLUSION: SEMS and APC are safe treatment options for restoration of the swallowing function in patients with obstructing GEJ adenocarcinoma. SEMS or APC are equivalent treatment modalities in terms of survival. PMID- 22677237 TI - Catheter-based renal denervation for treatment of resistant hypertension. AB - INTRODUCTION: Activation of renal sympathetic nerves is associated with the development of hypertension. Catheter-based renal sympathetic denervation with radiofrequency energy ablation is a new promising treatment option for resistant hypertension. We here report the first Danish experiences and results with this technique. MATERIAL AND METHODS: Nine patients with resistant hypertension and a day-time 24-hour ambulatory blood pressure (BP) of 152/89 mmHg +/- 10/10 (standard deviation) mmHg despite treatment with 5.4 +/- 1.4 anti-hypertensive drugs underwent catheter-based renal sympathetic denervation with the Symplicity catheter. RESULTS: No periprocedural complications or adverse events during follow-up were observed. Seven patients received complete ablation and two patients only partial ablation. Five patients responded to the treatment with a reduction in day-time 24-hour ambulatory BP from 158/94 +/- 13/9 mmHg to 139/82 +/- 10/8 mmHg (p < 0.05) at the one month follow-up and a reduction in the number of anti-hypertensive drugs from 5.4 +/- 1.6 to 3.4 +/- 0.9 (p < 0.05). BP in the remaining four patients was not significantly changed and antihypertensive therapy was not changed. CONCLUSION: Catheter-based renal sympathetic denervation is a feasible and in several cases also effective treatment option for patients with resistant hypertension. Adequately designed controlled trials are needed to assess the long-term safety and the full potential of this treatment. PMID- 22677238 TI - Socioeconomic factors may influence the surgical technique for benign hysterectomy. AB - INTRODUCTION: Owing to significantly improved outcomes, vaginal hysterectomy is the recommended standard approach when feasible in preference to abdominal hysterectomy. It is, however, not clear whether the use of vaginal hysterectomy varies with the women's socioeconomic background. MATERIAL AND METHODS: All 22,150 women registered in the Danish Hysterectomy Database in the 2004-2008 period were included in this cohort study and linked to central registers providing information on education, income and employment. Analyses were carried out using multiple logistic regression models. RESULTS: Among the 16,645 patients with information on all variables, 34% had a vaginal hysterectomy, while 60% had an abdominal and 6% a laparoscopic procedure. Women with a short education were more likely to undergo vaginal hysterectomy (30%) than women with a higher education (28%) (odds ratio (OR): 1.23; 95% confidence interval (CI): 1.10-1.38), but this association seemed to be fully explained by differences in surgery indication (OR: 0.99; CI: 0.87-1.13). Women out of work less often had a vaginal hysterectomy than women in work when adjusting for surgery indication (OR: 0.79; CI: 0.70-0.88). CONCLUSION: Small socioeconomic differences in surgical approach in hysterectomy were observed and were seemingly explained by clinical surgery indications, with the exception of women out of work for whom vaginal hysterectomy is used less often. PMID- 22677239 TI - Lymph node dissection in patients with malignant melanoma is associated with high risk of morbidity. AB - INTRODUCTION: Malignant melanoma is one of the most rapidly increasing cancer types globally, and it is by far the most serious skin cancer. Patients with a melanoma >= 1 mm in Breslow thickness are offered sentinel node (SN) biopsy and subsequent radical lymph node dissection if the biopsy is positive. The objective in the present paper was to describe post-operative complications in this group of patients. A standard operation and drainage regime was used. MATERIAL AND METHODS: This was a retrospective study based on 96 consecutive SN-positive patients with primary cutaneous malignant melanoma who underwent subsequent radical axillary or inguinal lymph node dissection. Fisher's exact test and Mann Whitney U-test were used to evaluate associations. RESULTS: In all, 57 patients were male and 39 female. A total of 71 had an axillary and 25 an inguinal operation. The median drainage period was seven days (2-15 days). Forty patients developed seroma which needed puncture; three of these cases were chronic, there was no difference between the two groups. Seroma puncture was only associated with infection in the inguinal group (p = 0.04). 25% in the axillary group were diagnosed with lymph oedema after three months versus 48% in the inguinal group (p = 0.04). A body mass index >= 25 kg/m2 was associated with a slight, but non significant increase in complications (p = 0.08). No association was found for smoking or co-morbidity. CONCLUSION: Patients undergoing axillary or inguinal lymph node dissection experience a significant number of complications, especially seroma and lymph oedema. Long-term complications are severe and can profoundly impact the patient's quality of life. PMID- 22677240 TI - Comprehensive geriatric assessment increases 30-day survival in the aged acute medical inpatients. AB - INTRODUCTION: Age and comorbidity are associated with length of stay (LOS) and mortality. Our aim was to compare acutely ill elderly medical patients in geriatric care with general medical care, and to examine the effects of comprehensive geriatric assessment (CGA). MATERIAL AND METHODS: In an observational study, we used data from patients aged 80+ years who had been acutely admitted to departments of medicine at Aarhus University Hospital in the period from 1 January 2009 to 31 December 2010. Age, comorbidity and LOS in the Geriatric Department (GD) were compared with those of the general medical departments (MD). A subgroup analysis was made on patients admitted during a 3.5 month period. RESULTS: A total of 3,877 patients were hospitalized of whom 27% were admitted to the GD. The mean age of the GD patients was 86.9 years versus 85.7 (p < 0.05). Comorbidity was higher in the GD patients than in the MD patients (p < 0.05). No difference was found in LOS. GD patients were hospitalized for median seven days versus median six days in MD patients (beta = 1.04 (95% confidence interval (CI): 0.98-1.10)). In the subgroup analysis (n = 496), no differences were shown in 30-day readmission (14% versus 13%) (odds ratio (OR) = 1.08 (95% CI: 0.57-2.02)). Thirty-day mortality in GD patients was lower than in MD patients (6% versus 13%) (OR = 0.40 (95% CI: 0.17-0.92)). CONCLUSION: An acutely ill elderly patient seems to benefit from CGA in a geriatric department. Short-term mortality is reduced despite higher age and comorbidity and the length of stay or readmission rate were not increased. TRIAL REGISTRATION: Clinicaltrials.gov - id: CGA-GD-2011 PMID- 22677241 TI - Positive experiences with a specialist as facilitator in general practice. AB - INTRODUCTION: The use of facilitators for quality improvement in general practice has accelerated during the past decade. As general practitioners (GPs) or pharmacists have typically been used as facilitators, there is a lack of knowledge of how other professionals function as facilitators. This article explores the experiences and assessments of GPs and nurses participating in a project in which a medical specialist (endocrinologist) acted as a facilitator for quality improvement. METHODS: This study is based on observations of facilitation sessions and interviews with the health professionals (13 GPs, four nurses, one endocrinologist) participating in a facilitation project in the Capital Region of Denmark. RESULTS: The facilitator sessions primarily focused on pharmacological issues related to diabetes treatment. The respondents described the facilitation sessions as a positive and motivating learning experience, and the majority of them were able to point to specific learning outcomes. CONCLUSION: The results suggest that for selected medical issues, a trained medical specialist can act as a facilitator in general practice to the satisfaction of GPs and staff. Future studies should assess the clinical effects of such facilitation programmes. PMID- 22677242 TI - Possible better long-term survival in left versus right-sided colon cancer - a systematic review. AB - INTRODUCTION: Colon cancer is one of the most frequent types of cancer in Denmark and the western world. Recent studies indicate that there are differences between right- and left-sided colon cancer with regard to epidemiology, clinical manifestation, pathology and prognosis. The present systematic literature review focuses on this subject. METHOD: PubMed, the Ovid Database and the Cochrane Library of Systematic Reviews were searched for relevant literature in October 2011. Only 17 studies fulfilled the inclusion criteria, which were 1) literature published after 1998, 2) written in Danish or English, and 3) peer-reviewed publication. RESULTS: We found that patients with right-sided colon cancer were older, more often females, possibly had more co-morbidities, had more advanced tumour stages, increased tumour sizes, more poorly differentiated tumours, different molecular biological tumour patterns and a poorer prognosis than patients with left-sided colon cancer. Multivariate analyses showed that age, gender, mode of presentation (emergency/elective), co-morbidity and stage had significant influence on survival, but it was uncertain whether tumour location itself had such an effect, though the different molecular biological patterns indicate this. CONCLUSION: The findings potentially have consequences for the planning of screening and treatment of colon cancer, but further research in the area is needed. PMID- 22677243 TI - Better treatment of outpatients with type 1 diabetes after introduction of continuous subcutaneous insulin infusion. AB - INTRODUCTION: Continuous subcutaneous insulin infusion (CSII) was introduced in the outpatient diabetes clinic in Fredericia, Denmark, in 2005. The aim of this study was to evaluate the quality of metabolic control and patient satisfaction in type 1 diabetic patients treated with CSII. MATERIAL AND METHODS: In 2009 2010, a database with registration of metabolic variables and patient satisfaction was established. The collected material is a combination of retrospective and prospective data. Patient satisfaction was measured by use of the Diabetes Treatment Satisfaction Questionnaire Status (DTSQs) and change (DTSQc) versions. RESULTS: By 31 December 2010, the database contained data from 68 active patients. Compared with before the initiation of CSII, glycohaemoglobin (HbA1c) had decreased significantly from 8.0% (5.8-13.7%) to 7.6% (6.1-9.5%). The improved glycaemic control was maintained each year until <= 4 years after initiation of CSII (p < 0.01).The fraction of patients with an HbA1c <= 7% had increased from 13% to 24%, the fraction of patients with an HbA1c > 9% had decreased from 18% to 3%, and the number of serious attacks of hypoglycaemia had decreased (p < 0.05). Only three episodes of ketoacidosis were observed. The DTSQs and DTSQc showed a higher patient satisfaction during CSII treatment (p < 0.01) than before its introduction. Compared with before the introduction of CSII, the patient satisfaction score had increased from 19 (12-33) to 34.5 (27 36) (p < 0.01). CONCLUSION: Type 1 diabetes patients who were changed from treatment with multi-injection therapy to CSII showed improved glycaemic control, a reduced number of hypoglycaemic attacks and improved and very high levels of patient satisfaction. PMID- 22677244 TI - Prolonged length of hospital stay in Denmark after nephrectomy. AB - INTRODUCTION: Implementation of the principles of a fast-track surgical programme resulted in a decrease in the length of hospital stay after open nephrectomies. The aim of this study was to describe the regional distribution of nephrectomies, postoperative hospital stay and mortality. MATERIAL AND METHODS: This study was based on data extracted from the Danish National Patient Registry for the 2000 2009-period. RESULTS: A total of 6,790 nephrectomies were performed. The mean postoperative stay and mortality decreased from 10.1 days and 2.6% during the 2000-2004-period to 8.3 days (p > 0.05) and 1.7% (p < 0.05) during the 2005-2009 period. A significant decrease in length of postoperative stay (6.4 versus 9.0 days; p < 0.05) and mortality (0.9% versus 2.1%; p < 0.05) was found between laparoscopic and open nephrectomies, respectively, during the 2005-2009-period. Nephrectomies performed by laparoscopic technique rose from 7.6% to 30.8% (p < 0.05) and laparoscopic nephroureterectomies from 1.7% to 10.3% (p < 0.05) from the 2000-2004-period to the 2005-2009-period. CONCLUSION: We recommend the implementation of fast-track surgery programmes to further decrease postoperative stay and mortality. A further increase in the use of laparoscopy is warranted. PMID- 22677245 TI - Most patients regain prefracture basic mobility after hip fracture surgery in a fast-track programme. AB - INTRODUCTION: Treatment of patients with hip fracture has improved over the past decade. Still, some patients do not regain independent mobility within their primary hospital stay even if they follow a multimodal fast-track surgical programme. The aim of the present article was to examine the validity of the preliminary prefracture New Mobility Score (NMS), age and fracture type as independent predictors of in-hospital outcome after hip fracture surgery. MATERIAL AND METHODS: The study comprised a total of 213 consecutive patients with a median age of 82 years who were admitted from their own home to a special hip fracture unit. Outcome variables were the regain of independency in basic mobility as evaluated by the Cumulated Ambulation Score, and discharge destination in the community. RESULTS: Multiple logistic regression analysis revealed that patients with a low prefracture NMS and/or an intertrochanteric fracture were 6.5 and four times more likely to not regain independency in basic mobility during admittance than patients with a high prefracture NMS level and a cervical fracture, respectively. In addition, the odds of not regaining independent mobility increased with age by 5% per year. The same three variables significantly increased the odds of patients not being discharged to their own home. CONCLUSION: Prefracture NMS, age and fracture type were confirmed as independent predictors of in-hospital outcome in patients with hip fracture who followed a multimodal rehabilitation concept. PMID- 22677246 TI - Nationwide tobacco surveys and sales data in Denmark from 1920 to 2010. AB - INTRODUCTION: Tobacco smoking is an important cause of premature death and morbidity in Denmark. It is therefore important to monitor tobacco consumption. In this paper, tobacco consumption in Denmark is illustrated by two methods: sale of tobacco products and smoking habit surveys. MATERIAL AND METHODS: Data on sale of tobacco products in Denmark were available for the 1920-2010-period. National smoking habit surveys were found through grey-zone literature, a PubMed search and a report on the Danish population's smoking habits. Ten smoking habit surveys were identified from the 1953-2010-period, three of which have data from multiple years and annual surveys from 1969 onwards. RESULTS: The changes in tobacco consumption found by the two methods were not parallel. Furthermore, there were significant differences between the proportions of smokers found in smoking habit questionnaires from the same year. This difference may be due to changes in cross border trade, smuggling, smokers' willingness to participate in smoking habit studies, recognition of own smoking and actual tobacco consumption, and differences in the composition of participants in the smoking habit studies both over time and between different studies. CONCLUSION: Both sales statistics and surveys have advantages and disadvantages. It may therefore be important to use both when estimating tobacco consumption. PMID- 22677247 TI - Increasing rate of angiotensin-converting enzyme inhibitor-related upper airway angio-oedema. AB - INTRODUCTION: The objective of this study was to evaluate whether the increased use of angiotensin-converting enzyme inhibitors (ACEI) has affected the rate of upper airway angio-oedema (AE). In addition, we evaluated the presentation and treatment of patients with upper airway AE. MATERIAL AND METHODS: This was a ten year retrospective study of 112 patients presenting with upper airway AE at The Department of Otorhinolaryngology, Aarhus University Hospital, Denmark. Incidence, presentation and treatment in the 2000-2004-period were compared to those of the 2005-2009-period. RESULTS: In the ten-year period, we found 112 AE patients of whom 39% were using ACEI. The relative risk of AE was 7.7 (p < 0.0001) among ACEI users. We found a 67% increase in AE in 2005-2009 compared with 2000-2004 which corresponds to a similar increase in ACEI use in the Danish population. The most frequent anatomic sites of involvement were the floor of the mouth and/or oropharynx including the base of the tongue. Two patients required intubation upon their arrival to the hospital. None progressed in airway obstruction requiring intubation later. None died. CONCLUSION: We found an increasing rate of ACEI-related upper airway AE over a ten-year period corresponding to greater use of ACEI in the population. With a relative risk of 7.7 and continuously increasing ACEI consumption, this condition will certainly require future attention and resources as almost one third of patients are admitted to an intensive care unit. PMID- 22677248 TI - Emergency teams in Danish emergency departments. AB - INTRODUCTION: The use of designated emergency teams for cardiac arrest and trauma patients is widely implemented. However, the use of designated teams in Danish emergency departments (EDs) has not been investigated. Our aim was to investigate the use and staffing of emergency teams in Danish EDs. MATERIAL AND METHODS: A cross-sectional questionnaire study was sent to all 20 Danish EDs designated for emergency care. RESULTS: The response rate was 95% (n = 19). Three EDs were excluded due to incomplete data. All EDs (n = 16) received critically ill patients, cardiac arrests and trauma patients. In all EDs, a designated team responded to cardiac arrest (CAT) and trauma patients (TT). Only 31% of EDs had access to a designated medical emergency team (MET). CAT consisted of a median of six (range 5-10) different personnel groups. Of these, three (1-6) were physicians and only one (0-2) was a senior physician. TTs consisted of a median of nine (7-11) different personnel groups. Of these, four (2-6) were physicians, and three (2-4) were senior physicians. In 25% of the EDs, there was no access to a MET. In 31% of the EDs, an ad hoc-team was created. In 14%, a team was created by the attending emergency physician. The staffing of ad hoc-teams relied on diagnosis, symptoms and triage scores. CONCLUSION: Designated teams for patients in cardiac arrest and trauma patients are available in all Danish EDs. More senior staff form part of trauma teams than cardiac arrest teams. There is limited access to designated teams caring for critically ill medical patients in Danish EDs. PMID- 22677249 TI - Acceptable results after self-expanding metallic stent treatment for dysphagia in non-resectable oesophageal cancer. AB - INTRODUCTION: Dysphagia is the most common symptom of malignant obstruction in the oesophagus and at the gastro-oesophageal junction (GEJ) region, and the relief of dysphagia plays a major role in palliative treatment of this condition. The aim of the present study was to evaluate the need for and nature of re intervention after self-expanding metallic stents (SEMS) insertion in patients who were palliated for cancer of the oesophagus or GEJ. MATERIAL AND METHODS: At a third-level referral centre in Denmark, all SEMS procedures were prospectively registered for SEMS characteristics and procedural events and data regarding re interventions and survival were retrieved retrospectively in a six-year inclusion period. RESULTS: A total of 108 stents were inserted into 87 patients (63 males and 23 females) with a median age of 71 years (range: 41-94 years). The primary SEMS used was Ultraflex in 77, Cook or Choo in seven and Wallstent in three cases. All but one SEMS were successfully placed, and no perforations occurred. Fifty patients had their dysphagia scores recorded. The average score before and after stent insertion was 2.4 and 0.8, respectively, (p < 0.01). Two-thirds of the patients needed late re-interventions. The most common problem was tissue/tumour ingrowth (n = 40). Seven patients (8%) experienced stent migration. The average re-intervention rate was 2.8 per patient. The median survival after SEMS was 116 days (range 2-866 days). The median time to first re-intervention was 44 days. CONCLUSION: SEMS treatment was a safe and effective palliation of malignant obstruction in the oesophagus and GEJ region, but the procedure was associated with a frequent need for re-interventions. PMID- 22677250 TI - Assessment of adult hip dysplasia and the outcome of surgical treatment. AB - Hip dysplasia and hip joint deformities in general are recognized as possible precursors of osteoarthritic development. Early and correct identification of hip dysplasia is important in order to offer timely joint preserving treatment. In the contemporary literature, several controversies exist, and some of these were the focus of this doctoral thesis. Categorized into subjects, the major findings and their possible importance are listed below. DIAGNOSTIC ASSESSMENT OF HIP DYSPLASIA: A multi-observer study quantified the variability of different methods for diagnostic assessment of hip dysplasia and osteoarthritis and resulted in general recommendations regarding diagnostic assessment of hip dysplasia. Pelvic tilt was shown to differ significantly between the supine and weight-bearing positions in patients with dysplastic hip joints. This is a finding that adds controversy to the application of neutral pelvic positioning during assessment of hip deformities because pelvic tilt affects the appearance of acetabular version. Weight-bearing assessment of acetabular version showed the presence of retroversion in 33% of dysplastic hips. The establishment of retroversion as a rather frequent entity in dysplastic hips is contradictory to the historical finding that hip dysplasia is characterized by insufficient anterior and lateral coverage. In general, the findings have important implications for orthopedic surgeons and radiologists dealing with diagnostic assessment of painful hips in young adults, and for surgeons planning and performing joint-preserving periacetabular osteotomies. ASSESSMENT OF ACETABULAR LABRAL TEARS IN HIP DYSPLASIA: The roles of ultrasound and clinical tests in acetabular labral tear diagnostics were established. After overcoming an initial learning curve, ultrasound investigation was highly reliable in diagnosing labral tears, whereas only a positive impingement or FABER test was reliable in identifying a labral tear. It seems that non-invasive and rapid ultrasound examination performed by an experienced examiner can potentially alter the traditional diagnostic algorithm in which magnetic resonance arthrography remains the gold standard. PERIACETABULAR OSTEOTOMY FOR SURGICAL TREATMENT OF HIP DYSPLASIA IN ADULTS: Encouraging hip joint survival and clinical outcome were reported at medium-term follow-up after periacetabular osteotomy. The small number of studies reporting the outcome beyond a 5-year follow-up is in contrast to the wide application of the periacetabular osteotomy. The performed analysis of predictors of conversion to total hip replacement following periacetabular osteotomy documented the importance of different biomechanical and degenerative factors. Knowledge about factors predicting early conversion to total hip replacement has the potential to refine patient selection and to improve treatment by periacetabular osteotomy. Cartilage thickness was documented to be preserved up to 2,5 years after periacetabular osteotomy. All but 1 hip joint had acetabular labral tears, thus indicating that the presence of labral tears does not accelerate cartilage degeneration after periacetabular osteotomy. PMID- 22677251 TI - Perfusion and metabolism imaging studies in Parkinson's disease. AB - Positron emission tomography (PET) and single photon emission computed tomography (SPECT) are important tools in the evaluation of brain blood flow and glucose metabolism in Parkinson's disease (PD). However, conflicting results are reported in the literature depending on the type of imaging data analysis employed. The present review gives a comprehensive summary of the perfusion and metabolism literature in the field of PD research, including quantitative PET studies, normalized PET and SPECT studies, autoradiography studies in animal models of PD, and simulation studies of PD data. It is concluded that PD most likely is characterized by widespread cortical hypometabolism, probably even at early disease stages. Widespread subcortical hypermetabolism is probably not a feature of PD, although certain small basal ganglia structures, such as the external pallidum, may display true hypermetabolism in the absolute sense. This observation is also in agreement with the animal literature. PMID- 22677253 TI - Treatment for hepatitis B virus (HBV) and hepatitis C virus (HCV) infection - Danish national guidelines 2011. AB - The Danish Society of Infectious Diseases and Danish Society of Gastroenterology and Hepatology set up a committee in 2007 to produce national guidelines for treatment of viral hepatitis B and C. The 2011 version of the guidelines have been endorsed by the scientific societies and are presented below. Annual updates will be available at the websites of the societies. As this present English version has been written six months after the Danish 2011 version, it contains minor changes that will be integrated in the Danish 2012 version, available at the end this year. EPIDEMIOLOGY: Viral hepatitis is not common in Denmark. The prevalence has not been determined by national surveys, but it is estimated that 10,000-15,000 patients are chronically infected with hepatitis B and 15,000 20,000 with chronic hepatitis C. The majority of patients with HBV infection in Denmark are emigrants from high endemic countries, probably infected at birth or early childhood in their country of origin, while the majority of patients with HCV infection have been infected by drug use. For both groups it is estimated that only half of the patients have been diagnosed, of whom only 20% attends specialized care for their chronic viral hepatitis. CLINICAL CARE: According to the Danish National Board of Health, patients with chronic viral hepatitis should be followed with regular intervals, at clinics specialized in either infectious diseases or gastroenterology/hepatology. The primary aim is to identify patients with significant liver disease to initiate treatment in order to prevent development of cirrhosis and death. This is primarily done by liver biopsy, but screening for fibrosis with non-invasive methods such as elastography may be sufficient in some patients. Patients with established cirrhosis should enter screening programs for complications such as esophageal varices and hepatocellular carcinoma. PMID- 22677252 TI - Natriuretic peptides as therapy in cardiac ischaemia/reperfusion. AB - Natriuretic peptides elicit vasodilation, increased sodium excretion and concomitant diuresis, and counteract the RAAS. In the heart itself, natriuretic peptides may also act anti-inflammatory and antifibrotic. This has led to the pursuit of natriuretic peptides and chemically modified peptides as adjunctive therapy in myocardial ischaemia. However, natriuretic peptide infusion may also influence the endogenous natriuretic peptide response and lipid accumulation. We hypothesised that a) natriuretic peptide infusion (BNP and CD-NP) is cardiomyocyte protective, b) affects the endogenous response, and c) facilitate cardiac lipid accumulation. We examined these effects in a minimally invasive porcine model of regional cardiac ischaemia and reperfusion. The studies were supplemented by a 48-hour porcine model of ischemia and reperfusion as well as an in vitro study of BNP administered in a HL-1 cell model of "ischaemia/reperfusion". Infarct size was determined by TTC staining, plasma troponin T release, and total RNA integrity in cardiac tissue samples. The endogenous response was assessed by a processing-independent proANP immunoassay and mRNA quantitation. Lipids in plasma and myocardial tissue were determined by TLC. The studies show that natriuretic peptides decrease cardiomyocyte damage, possibly partly through indirect mechanisms. Furthermore, BNP infusion completely inverts the endogenous response, whereas CD-NP infusion does not. Finally, both natriuretic peptides increase plasma free fatty acids, which is associated with an increased cardiac lipid accumulation in non-ischaemic myocardium. In conclusion, the studies suggest that natriuretic peptides are beneficial in terms of reduced cardiac injury. In addition, the endogenous natriuretic peptide response is inverted. The results advocate for pursuing natriuretic peptide treatment in ischaemia/reperfusion damage. However, the metabolic consequences in a cardiac tissue challenged by ischaemia should be pursued before testing the peptides in patients. PMID- 22677254 TI - Time constant of the cerebral arterial bed in normal subjects. AB - The time constant of cerebral arterial bed (in brief time constant) is a product of brain arterial compliance (C(a)) and resistance (CVR). We tested the hypothesis that in normal subjects, changes in end-tidal CO(2) (EtCO(2)) affect the value of the time constant. C(a) and CVR were estimated using mathematical transformations of arterial pressure (ABP) and transcranial Doppler (TCD) cerebral blood flow velocity waveforms. Responses of the time constant to controlled changes in EtCO(2) were compared in 34 young volunteers. Hypercapnia shortened the time constant (0.22 s [0.17, 0.26] vs. 0.16 s [0.13, 0.20]; p = 0.000001), while hypocapnia lengthened the time constant (0.22 s [0.17, 0.26] vs. 0.23 s [0.19, 0.32]; p < 0.0032). The time constant was negatively correlated with changes in EtCO(2) (R(partial) = -0.68, p < 0.000001). This was associated with a decrease in CVR when EtCO(2) increased (R(partial) = -0.80, p < 0.000001) and C(a) remained independent of changes in EtCO(2). C(a) was negatively correlated with mean ABP (R(partial) = -0.68, p < 0.000001). In summary, the time constant shortens with increasing EtCO(2). Its potential role in cerebrovascular investigations needs further studies. PMID- 22677255 TI - Effective gene transfer into central nervous system following ultrasound microbubbles-induced opening of the blood-brain barrier. AB - To investigate whether ultrasound-targeted microbubble destruction (UTMD) could transfer gene into central nervous system (CNS) following blood-brain barrier disruption (BBBD), DNA-loaded microbubbles were infused into the mice intravenously following ultrasonic exposure. Opening of the BBB, changes of mRNA and expression of enhanced green fluorescent protein (EGFP), and safety evaluation were measured. By UTMD, EGFP were substantially expressed in the cytoplasm of the neurons at the sonicated area with minor erythrocytes extravasation and the mRNA and expression of EGFP were markedly enhanced by about 15-fold and 10-fold, respectively, than that with US alone (p < 0.01). No EGFP was detected in the mice treated with DNA-loaded microbubbles or plasmid alone. The gene expression reached a climax at 48 h, gradually reduced to a much lower level thereafter. These results demonstrated UTMD could effectively enhance exogenous gene delivery and expression in CNS following BBBD, and this technique may provide a new method for CNS gene therapy. PMID- 22677256 TI - Computing myocardial motion in 4-dimensional echocardiography. AB - We describe a novel method for computing dense 3D myocardial motion with high accuracy in four-dimensional (4D) echocardiography (3 dimensions spatial plus time). The method is based on a classic variational optical flow technique but exploits modern developments in optical flow research to utilize the full capabilities of 4D echocardiography. Using a variety of metrics, we present an in depth performance evaluation of the method on synthetic, phantom, and intraoperative 4D transesophageal echocardiographic data. When compared with state-of-the-art optical flow and speckle tracking techniques currently found in 4D echocardiography, the method we present shows notable improvements in error rates. We believe the performance improvements shown can have a positive impact when the method is used as input for various applications, such as strain computation, biomechanical modeling, and automated diagnostics. PMID- 22677257 TI - Active immunotherapy for Alzheimer's disease. PMID- 22677259 TI - Trends in sinonasal cancer in The Netherlands: more squamous cell cancer, less adenocarcinoma. A population-based study 1973-2009. AB - BACKGROUND: Cancer of the nasal cavity or the paranasal sinuses (sinonasal cancer) is rare. Sinonasal cancer has been associated with various occupational risk factors such as exposure to dust of hard wood and leather. Also, a relationship with smoking habits has been suggested. We studied the long term trends in incidence to evaluate a putative effect of past preventive measures or changes in risk factors. DESIGN: A retrospective population-based descriptive study. OBJECTIVE: To interpret the long term trends in incidence of sinonasal cancer in The Netherlands. METHODS: Data of all 3329 patients >15 years registered during 1989-2009 by the Netherlands Cancer Registry (NCR) were analysed, by data of 447 patients registered by the Eindhoven Cancer Registry (ECR) during 1973-2009 were analysed separately. Information on patients and tumour characteristics was obtained from both registries. The incidence was calculated per 1,000,000 person years and standardised using the European Standard Population. RESULTS: Squamous cell carcinoma (SCC) was the most prominent histological type (48%), followed by adenocarcinoma (15%) and melanoma (8%). SCC was more frequently located in the nasal cavity or sinus maxillaris, but adenocarcinoma was more located in the ethmoid sinus. The male incidence increased during 1973-1995 with a peak of 15/1,000,000/year, decreasing since then to 11/1,000,000/year due to a declining incidence of both SCC and adenocarcinoma. In females the incidence remained stable around 5/1,000,000/year up to 2006 and increased to 7.5/1,000,000 in 2009 as a result of more SCC. The male/female ratio for SCC decreased from 2.7 to 2.0, and for adenocarcinoma from 3.4 to 2.8 since 1989. CONCLUSIONS: The higher incidence in males and the different trends in incidence in males and females may reflect differences in previous exposure to risk factors. Adenocarcinoma, related to occupational exposures, tend to decline. The trends in both male and female sinonasal SCC are comparable with the trends in lung cancer. PMID- 22677258 TI - Safety, tolerability, and antibody response of active Abeta immunotherapy with CAD106 in patients with Alzheimer's disease: randomised, double-blind, placebo controlled, first-in-human study. AB - BACKGROUND: Immunotherapy targeting the amyloid beta (Abeta) peptide is a potential strategy to slow the progression of Alzheimer's disease. We aimed to assess the safety and tolerability of CAD106, a novel active Abeta immunotherapy for patients with Alzheimer's disease, designed to induce N-terminal Abeta specific antibodies without an Abeta-specific T-cell response. METHODS: We did a phase 1, double-blind, placebo-controlled, 52-week study in two centres in Sweden. Participants, aged 50-80 years, with mild-to-moderate Alzheimer's disease were entered into one of two cohorts according to time of study entry and then randomly allocated (by use of a computer-generated randomisation sequence) to receive either CAD106 or placebo (4:1; cohort one received CAD106 50 MUg or placebo, cohort two received CAD106 150 MUg or placebo). Each patient received three subcutaneous injections. All patients, caregivers, and investigators were masked to treatment allocation throughout the study. Primary objectives were to assess the safety and tolerability of CAD106 and to identify the Abeta-specific antibody response. Safety assessment was done by recording of all adverse events, assessment of MRI scans, physical and neurological examinations, vital signs, electrocardiography, electroencephalography, and laboratory analysis of blood and CSF. Patients with Abeta-IgG serum titres higher than 16 units at least once during the study were classified as responders. This study is registered with ClinicalTrials.gov, number NCT00411580. FINDINGS: Between August, 2005, and March, 2007, we randomly allocated 31 patients into cohort one (24 patients to CAD106 treatment and seven to placebo) and 27 patients into cohort two (22 patients to CAD106 treatment and five to placebo). 56 of 58 patients reported adverse events. In cohort one, nasopharyngitis was the most commonly reported adverse event (10 of 24 CAD106-treated patients). In cohort two, injection site erythema was the most commonly reported adverse event (14 of 22 CAD106-treated patients). Overall, nine patients reported serious adverse events--none was thought to be related to the study drug. We recorded no clinical or subclinical cases of meningoencephalitis. 16 of 24 (67%) CAD106-treated patients in cohort one and 18 of 22 (82%) in cohort two developed Abeta antibody response meeting pre-specified responder threshold. One of 12 placebo-treated patients (8%) had Abeta-IgG concentrations that qualified them as a responder. INTERPRETATION: Our findings suggest that CAD106 has a favourable safety profile and acceptable antibody response in patients with Alzheimer's disease. Larger trials with additional dose investigations are needed to confirm the safety and establish the efficacy of CAD106. FUNDING: Novartis Pharma AG. PMID- 22677261 TI - Urinary sediment findings in acute interstitial nephritis. PMID- 22677260 TI - Randomised phase II/III study of docetaxel with or without risedronate in patients with metastatic Castration Resistant Prostate Cancer (CRPC), the Netherlands Prostate Study (NePro). AB - BACKGROUND: This multicentre, randomised, open label, phase II/III study aimed to investigate the potential benefit of adding risedronate (R) to docetaxel (D) in patients with metastatic Castration Resistant Prostate Cancer (CRPC). PATIENTS AND METHODS: CRPC patients with bone metastasis were randomly assigned to receive D 75 mg/m(2) every 3 weeks and prednisone as first line chemotherapy, with or without R 30 mg oral once daily. The primary end-point was time to progression (TTP). A composite end-point of objective progression by RECIST criteria, PSA progression, or pain progression, whichever occurred first, was applied. The study had 80% power to detect an improvement of 30% in median TTP in the DR group (two-sided alpha=0.05). RESULTS: Five hundred and ninety-two men (301 D versus 291 DR) were randomised. TTP was 7.4 [D] versus 6.5 [DR] months (p=0.75). PSA and pain response rates were similar, 66.3% [D] versus 65.9% [DR] and 27.9% [D] versus 31.2% [DR], respectively. Median overall survival (OS) was 18.4 [D] versus 19.2 [DR] months (p=0.33). There were no differences in toxicity. CONCLUSION: The addition of the third generation bisphosphonate, risedronate, in the setting of effective first line docetaxel based chemotherapy did not increase efficacy, as indicated by the lack of improvement in TTP, OS, PSA- and pain response. PMID- 22677262 TI - In vitro evaluation of single- and multi-strain probiotics: Inter-species inhibition between probiotic strains, and inhibition of pathogens. AB - Many studies comparing the effects of single- and multi-strain probiotics on pathogen inhibition compare treatments with different concentrations. They also do not examine the possibility of inhibition between probiotic strains with a mixture. We tested the ability of 14 single-species probiotics to inhibit each other using a cross-streak assay, and agar spot test. We then tested the ability of 15 single-species probiotics and 5 probiotic mixtures to inhibit Clostridium difficile, Escherichia coli and S. typhimurium, using the agar spot test. Testing was done with mixtures created in two ways: one group contained component species incubated together, the other group of mixtures was made using component species which had been incubated separately, equalised to equal optical density, and then mixed in equal volumes. Inhibition was observed for all combinations of probiotics, suggesting that when used as such there may be inhibition between probiotics, potentially reducing efficacy of the mixture. Significant inter species variation was seen against each pathogen. When single species were tested against mixtures, the multi-species preparations displayed significantly (p < 0.05 or less) greater inhibition of pathogens in 12 out of 24 cases. Despite evidence that probiotic species will inhibit each other when incubated together in vitro, in many cases a probiotic mixture was more effective at inhibiting pathogens than its component species when tested at approximately equal concentrations of biomass. This suggests that using a probiotic mixture might be more effective at reducing gastrointestinal infections, and that creating a mixture using species with different effects against different pathogens may have a broader spectrum of action that a single provided by a single strain. PMID- 22677263 TI - Risk and prognostic factors among patients with bacteremia due to Eggerthella lenta. AB - Eggerthella lenta is a Gram-positive non-spore forming anaerobic commensal bacilli that can cause bacteremia due to abdominal or soft tissue sources. Patients are frequently bedridden and infection is associated with a high mortality rate. Absence of fever at presentation and need for ICU stay are risk factors for 30-day mortality. PMID- 22677264 TI - Prediction of postprandial blood glucose under uncertainty and intra-patient variability in type 1 diabetes: a comparative study of three interval models. AB - The behavior of three insulin action and glucose kinetics models was assessed for an insulin therapy regime in the presence of patient variability. For this purpose, postprandial glucose in patients with type 1 diabetes was predicted by considering intra- and inter-patient variability using modal interval analysis. Equations to achieve optimal prediction are presented for models 1, 2 and 3, which are of increasing complexity. The model parameters were adjusted to reflect the "same" patient in the presence of variability. The glucose response envelope for model 1, the simplest insulin-glucose model assessed, included the responses of the other two models when a good fit of the model parameters was achieved. Thus, under variability, simple glucose-insulin models may be sufficient to describe patient dynamics in most situations. PMID- 22677265 TI - [Coronary vasospasm in general anaesthesia induction]. AB - Coronary artery vasospasm in the induction of general anaesthesia is a rarely reported complication in our environment, owing to its low incidence or due to having disappeared. We present a case of a previously healthy woman, scheduled for shoulder arthroscopy, who in the anaesthetic induction had a ventricular tachycardia, which spontaneously reverted to sinus rhythm with ST elevation on the left side, and which was diagnosed and treated immediately by using angiography. The importance of the case is based on the lack of references found, and on being rarely reported in health patients during the induction of general anaesthesia, and with an immediate diagnosis and resolving using angiography. PMID- 22677267 TI - Genomic organization of selected genes in the small monogonont rotifer, Brachionus koreanus. AB - Information of genome structure with its size variation may provide important clues for evolutionary processes at lower taxon level in eukaryotes. Here, we analyzed the compact genome structure of the monogonont rotifer, Brachionus koreanus in the light of transphyletic genome comparison and economic genome usage. To confirm the genome compactness of B. koreanus, we compared the genomic structure of several selected genes with those of human and pufferfish. For example, one of the large genes, DNA-dependent protein kinase (DNA-PK) with dimeric protein Ku70 and Ku80, showed high similarity, even though genomic DNA lengths were quite different. The replication protein As (RPAs) as a heterotrimeric protein also showed a compact genomic structure including all the essential domains and motifs in B. koreanus. Regarding transmembrane protein containing genes, the B. koreanus P-glycoprotein (P-gp) showed exactly the same topology of the TM domain compared to those of human and pufferfish, even though it had a compact genome structure. In addition, the gene structure of an inducible repair enzyme O(6)-methylguanine DNA methyltransferase (O(6)-MGMT) of B. koreanus showed the highest compactness among the genes tested. The objective of this report is to evaluate the potential for whole genome sequencing and functional genomic research using the monogonont rotifer B. koreanus as a non model organism that plays important roles in aquatic food-webs. Subsequently, we discussed possible reasons for compact genome structures as well as small and fewer introns from several perspectives. We conclude that the small size genome of B. koreanus would make this species potentially useful for comparative genome structure analysis of non-model species through whole genome sequencing and genetic mapping. PMID- 22677266 TI - Comparison of normalization methods for measuring immune markers in cervical secretion specimens. AB - Ophthalmic sponges are used to collect undiluted cervical secretions for assessment of markers of genital tract immunity. Heterogeneity in absorbed and extracted sample volumes requires normalization in order to make valid inter individual comparisons. We evaluated the performance of adjustment by weight and total protein on normalizing inter-individual variability of immune marker measurement due to differences in volume collection. Normalization to total protein resulted in a minimal loss of usable specimens and a significant reduction in the correlation of immune marker concentration to specimen weight compared to weight adjustment. Total protein normalization appeared to be more effective than weight adjustment in reducing the dependence of cervical immune marker concentrations on differences in specimen volume. PMID- 22677268 TI - Association of interleukin-(IL)10 haplotypes and serum IL-10 levels in the progression of childhood immune thrombocytopenic purpura. AB - Derangement of genetic and immunological factors seems to have a pivotal role in the pathophysiology of immune thrombocytopenic purpura (ITP). We investigated interleukin(IL)-10 genetically determined expression in children with an acute progression of ITP (n=41) compared to young patients with chronic ITP (n=44) and healthy controls (n=60), and attempted to correlate IL-10 production with the course of the disease. We genotyped our study population for three single nucleotide polymorphisms at positions -1082 (A/G), -819 (C/T) and -592 (C/A) in the promoter region of the IL-10 gene. IL-10 levels were measured by enzyme linked immunoassay. The IL-10 production in our study population was significantly higher in patients carrying the GCC haplotype than those bearing ACC and ATA haplotypes (6.9 +/- 1.5 vs 3.6 +/- 0.8 vs 3.3 +/- 0.3, p=0.03). The serum concentration of IL-10 was significantly higher in patients with an acute course of their disease, who mainly carried the GCC haplotype (92%), compared to chronic subjects, bearing the non-GCC haplotypes, and controls [17 pg/mL (1.7-18) vs 3.5 pg/mL (0.6-11) vs 3 pg/mL (1-7), p<0.01)]. Our findings show that patients carrying the GCC-high producer IL-10 haplotype have an acute development of ITP and that IL-10 levels might represent a useful predictive biomarker of the disease course. PMID- 22677269 TI - Correlation between TGF-beta1-509 C>T polymorphism and risk of digestive tract cancer in a meta-analysis for 21,196 participants. AB - The association between transforming growth factor beta1 (TGF-beta1)-509 C>T and risk of digestive tract cancer (DTC) remained uncertain as previous studies reported conflicting results. The aim of this study was to assess the association by using a meta-analysis. The databases of MEDLINE, EMBASE and WANGFANG (Chinese database) were retrieved, and latest update was on 2nd February, 2012. Pooled odds ratio and 95% confidence interval (OR and 95% CI) were calculated by using a fixed- or random-effect model. Ultimately, twenty nine case-control studies with 8664 cases and 12,532 controls were included in this meta-analysis. Overall, there was no association between TGF-beta1-509 C>T and risk of DTC in all genetic comparison models (OR and 95% CI: 0.96 and 0.81-1.15 for TT vs. CC, 0.98 and 0.91 1.05 for T carriers vs. C carriers). When subgroup analyses were conducted according to ethnicity, types of cancer and sample size, T allele was significantly associated with decreased risk of DTC for Caucasians and for large sample-sized studies, and was associated with decreased risk of colorectal cancer (OR and 95% CI for TT vs. CC: 0.82 and 0.70-0.97 for Caucasians, 0.80 and 0.68 0.98 for large sample-sized studies, 0.78 and 0.62-0.97 for colorectal cancer). This study indicated that TGF-beta1-509 C>T polymorphism was probably associated with risk of DTC, especially for Caucasians. Because of modest limitation, our findings should be confirmed by future studies. PMID- 22677270 TI - Zebrafish responds differentially to a robotic fish of varying aspect ratio, tail beat frequency, noise, and color. AB - In this paper, we present a bioinspired robotic fish designed to modulate the behavior of live fish. Specifically, we experimentally study the response of zebrafish to a robotic fish of varying size, color pattern, tail beat frequency, and acoustic signature in a canonical preference test. In this dichotomous experimental protocol, focal fish residing in the center focal compartment of a three-chambered test tank are confronted with pairs of competing stimuli, including various robots and the empty compartment, and their position is observed over time to measure preference. Fish behavior is classified into three main locomotory patterns to further dissect the complex behavior of zebrafish interacting with robots. A total of twelve experimental conditions is studied to isolate the effect of different elements of the robot design and provide general techniques for enhancing the attraction of zebrafish. We find that matching the aspect ratio and the visual appearance of the robotic fish with the target species increases the attraction experienced by zebrafish. We also find that the robot's tail beat frequency does not play a dominant role on fish attraction, suggesting that this parameter could be optimized based on engineering needs rather than biological cues. On the other hand, we find that varying the aspect ratio and coloration of the robot strongly influences fish preference. PMID- 22677271 TI - Alcohol preference, behavioural reactivity and cognitive functioning in female rats exposed to a three-bottle choice paradigm. AB - Alcohol abuse is a substantial and growing health problem in Western societies. In the last years in vivo and in vitro studies have suggested that males and females display a different alcohol drinking behaviour, with swingeing differences not only in the propensity for alcohol use but also in the metabolic and behavioural consequences. In this study we investigated, in adult female rats, ethanol self-administration and preference pattern using a 3-bottle paradigm with water, 10% ethanol solution, and white wine (10%, v/v), along a four-week period. The influence of alcohol free-access on explorative behaviour in the open field (OF), and on spatial learning and reference memory in the Morris water maze (MWM) were also evaluated. Our results indicate that: (i) female rats show a higher preference for alcohol, in the first two weeks of the paradigm, displaying a higher consumption of 10% ethanol solution than white wine; in the last two weeks, they reduce their alcoholic preference, drinking the same moderate amounts of the two alcoholic beverages; (ii) at the fourth week of the free-access paradigm rats show a lower explorative behaviour in the open field and a worsening in spatial memory retention in the Morris water maze. In conclusion our data suggest that, despite the ability to self-regulate alcohol intake, female rats suffer from relevant impairments in spatial memory retention and cognitive flexibility, displaying a sexually dimorphic modification in the adaptive strategies. PMID- 22677272 TI - Intact and impaired executive abilities in the BTBR mouse model of autism. AB - BTBR T+tf/J (BTBR) inbred mice are frequently used as a model of autism spectrum disorders (ASD) as they display social deficits and repetitive behaviors that resemble the symptoms of the human syndrome. Since deficits on tasks that measure cognitive (executive) control are also reliable phenotypes in ASD, we wanted to determine whether executive abilities were compromised in the mouse model. BTBR mice were trained on two visual discrimination paradigms requiring differing degrees of cognitive control. BTBR mice performed normally on a visual discrimination reversal where rule switching was relatively automatic, but were severely impaired on a task-switch paradigm that required the active use of contextual information to switch between rules in a flexible manner. The present findings further characterize the behavior of BTBR mice as a model of ASD. Moreover, the demonstration of both intact and impaired executive functions in BTBR mice illustrates the importance of developing new cognitive assays for comprehensive behavioral assessment of mouse models of human brain disorders. PMID- 22677273 TI - Gabra5-gene haplotype block associated with behavioral properties of the full agonist benzodiazepine chlordiazepoxide. AB - The gabra5 gene is associated with pharmacological properties (myorelaxant, amnesic, anxiolytic) of benzodiazepines. It is tightly located (0.5 cM) close to the pink-eyed dilution (p) locus which encodes for fur color on mouse chromosome 7. We tested the putative role of the gabra5 gene in pharmacological properties of the full non specific agonist chlordiazepoxide (CDP), using behavioral and molecular approaches in mutated p/p mice and wild type F2 from crosses between two multiple markers inbred strain ABP/Le and C57BL/6By strain. From our results, using rotarod, light-dark box, elevated maze and radial arm maze tests, we demonstrate that p/p mice are more sensitive than WT to the sensory motor, anxiolytic and amnesic effect of CDP. This is associated with the presence of a haplotypic block on the murine chromosome 7 and with an up regulation of gabra5 mRNAs in hippocampi of p/p F2 mice. PMID- 22677274 TI - Dantrolene blockade of ryanodine receptor impairs ethanol-induced behavioral stimulation, ethanol intake and loss of righting reflex. AB - Calcium has been characterized as one of the most ubiquitous, universal and versatile intracellular signals. Among other substances with the ability to alter intracellular calcium levels, ethanol has been described as particularly relevant because of its social and economic impact. Ethanol effects on calcium distribution and flux in vitro have been widely studied, showing that acute ethanol administration can modulate intracellular calcium concentrations in a dose dependent manner. Intracellular calcium released from the endoplasmic reticulum plays a determinant role in several cellular processes. In this study, we aim to assess the effect of dantrolene, a ryanodine receptor antagonist, on three different ethanol-elicited behaviors: locomotor activity, loss of righting reflex and ethanol intake. Mice were challenged with an injection of dantrolene (0-5 mg/kg, i.p.) 30 min before ethanol (0-4 g/kg, i.p.) administration. Animals were immediately placed in an open field cylinder to monitor distance travelled horizontally or in a V-shaped trough to measure righting reflex recovery time. For ethanol intake, dantrolene (0-5mg/kg, i.p.) was administered 30 min before ethanol (20%, v/v) exposure, following a drinking in the dark paradigm. Our results showed that dantrolene selectively reduces ethanol-induced stimulation, loss of righting reflex, and ethanol intake in a dose dependent manner. Together, these data suggest that intracellular calcium released from the endoplasmic reticulum may play a critical role in behavioral effects caused by ethanol, and point to a calcium-dependent pathway as a possible cellular mechanism of action for ethanol. PMID- 22677275 TI - Cerebral correlates of visual lateralization in Sepia. AB - The common cuttlefish, Sepia officinalis (cephalopod mollusc) has recently become a relevant model for studying the setting-up of brain asymmetry among invertebrates. As the animals age from 3 to 30 days post hatching, they progressively develop a left-turning bias resulting from an eye-use preference. The aim of this study is to investigate whether anatomical (vertical, peduncle, inferior buccal, and optic lobes) or neurochemical (monoamines in optic lobes) brain asymmetries are present in the cuttlefish brain at 3 or at 30 post hatching days; and whether these correlate with side-turning preferences. We here find brain and behavioral asymmetry only at 30 post hatching days. Cuttlefish displayed a significant population bias towards a larger right peduncle lobe, and higher monoamine concentration in the left optic lobe (i.e. serotonin, dopamine and noradrenaline). None of these brain asymmetries were correlated to the studied side-turning bias. However, we found individual variation in the magnitude of the vertical and optic lobes asymmetry. A striking correlation was found with the behavioral results: the larger the right optic lobe and the right part of the vertical lobe, the stronger the bias to turn leftwards. To our knowledge, this is the first study to demonstrate a relationship at the individual level between brain and behavioral asymmetries in invertebrates. PMID- 22677276 TI - Development and application of a new method to investigate cognition in newborn guppies. AB - The study of cognitive abilities generally requires that each subject be assessed individually, but social isolation can be stressful, especially for newborns and young individuals. This study aimed to design learning protocols for newly born guppies based on knowledge of their social needs. In Experiment 1, in the first two weeks of life, guppies were much less gregarious than adults but spent significantly more time near social companions than near an empty compartment. When given the choice between social companions and their own mirror image (Experiment 2), they did not exhibit a preference for either virtual or real fish, indicating the possibility of using mirrors as a substitute for social companions during learning experiments. Using these data, we tested two new procedures for studying learning and memory in very young fish. Experiment 3 was a modification of the one-trial test developed for mammals in which subjects are required to discriminate between one new object and one they previously and briefly experienced. Five-day-old guppies allowed to familiarize with a tridimensional object for 20 min proved able, 30 min later, to discriminate the familiar object from a novel one differing in shape and color. For Experiments 4 and 5, we adapted a protocol for discrimination learning for adult fish: two stimuli were repeatedly introduced at opposite ends of the home tank, one reinforced with food. Using this method, we showed that nine-day-old guppies can significantly discriminate two geometric figures (a triangle from a circle) after only twelve reinforced trials. PMID- 22677277 TI - A larval zebrafish model of bipolar disorder as a screening platform for neuro therapeutics. AB - Modelling neurological diseases has proven extraordinarily difficult due to the phenotypic complexity of each disorder. The zebrafish has become a useful model system with which to study abnormal neurological and behavioural activity and holds promise as a model of human disease. While most of the disease modelling using zebrafish has made use of adults, larvae hold tremendous promise for the high-throughput screening of potential therapeutics. The further development of larval disease models will strengthen their ability to contribute to the drug screening process. Here we have used zebrafish larvae to model the symptoms of bipolar disorder by treating larvae with sub-convulsive concentrations of the GABA antagonist pentylenetetrazol (PTZ). A number of therapeutics that act on different targets, in addition to those that have been used to treat bipolar disorder, were tested against this model to assess its predictive value. Carbamazepine, valproic acid, baclofen and honokiol, were found to oppose various aspects of the PTZ-induced changes in activity. Lidocaine and haloperidol exacerbated the PTZ-induced activity changes and sulpiride had no effect. By comparing the degree of phenotypic rescue with the mechanism of action of each therapeutic we have shown that the low-concentration PTZ model can produce a number of intermediate phenotypes that model symptoms of bipolar disorder, may be useful in modelling other disease states, and will help predict the efficacy of novel therapeutics. PMID- 22677279 TI - Entomopathogenic nematodes. PMID- 22677280 TI - Retrotransposons. AB - June 27, 1970 was a significant day for our understanding of both the flow of information in biological systems and the evolution of eukaryotic genomes as this was the day that Nature published back-to-back papers reporting the discovery of an enzyme that copies RNA into DNA. This soon became known as reverse transcriptase and the RNA tumour viruses in which it was detected were renamed retroviruses. The realisation that retroviruses can convert their genomic RNA into DNA provided a route by which they could integrate into the chromosomes of infected cells as Howard Temin and his colleagues had proposed some years earlier. At the time it was thought that the ability to copy RNA into DNA would be confined to retroviruses. One of the more startling outcomes of whole genome DNA sequencing has been the discovery that eukaryotes can have more reverse transcriptase genes than genes coding for any other protein, and that the largest single component of many eukaryotic genomes has been generated by reverse transcription. PMID- 22677278 TI - The ventricular volume variability study of the Pediatric Heart Network: study design and impact of beat averaging and variable type on the reproducibility of echocardiographic measurements in children with chronic dilated cardiomyopathy. AB - BACKGROUND: Clinical trials often rely on echocardiographic measures of left ventricular size and function as surrogate end points. However, the quantitative impact of factors that affect the reproducibility of these measures is unknown. To address this issue, the National Heart, Lung, and Blood Institute-funded Pediatric Heart Network designed a longitudinal observational study of children with known or suspected dilated cardiomyopathy aged 0 to 22 years from eight pediatric clinical centers. METHODS: Clinical data were collected together with 150 echocardiographic indices of left ventricular size and function. Separate observers performed duplicate echocardiographic imaging. Multiple observers performed measurements from three cardiac cycles to enable assessment of intraobserver and interobserver variability. The impacts of beat averaging (BA), observer type (local vs core), and variable type (areas, calculations, dimensions, slopes, time intervals, and velocities) on measurement reproducibility were studied. The outcome measure was percentage error (100 * difference/mean). RESULTS: Of 173 enrolled subjects, 131 met criteria for dilated cardiomyopathy. BA, variable type and observer type all influenced percentage error (P < .0001). Core interobserver percentage error (medians, 11.4%, 10.2%, and 9.3% for BA using one, two, and three beats, respectively) was approximately twice the intraobserver percentage error (medians, 6.3%, 4.9%, and 4.2% for BA using one, two, and three beats, respectively). Slopes and calculated variables exhibited high percentage error despite BA. Chamber dimensions, areas, velocities, and time intervals exhibited low percentage error. CONCLUSIONS: This comprehensive evaluation of quantitative echocardiographic methods will provide a valuable resource for the design of future pediatric studies. BA and a single core lab observer improve the reproducibility of echocardiographic measurements in children with dilated cardiomyopathy. Certain measurements are highly reproducible, while others, despite BA, are poorly reproducible. PMID- 22677281 TI - Neandertal and Denisovan retroviruses. PMID- 22677282 TI - Population divergence in East African coelacanths. AB - The coelacanth, Latimeria chalumnae, occurs at the Eastern coast of Africa from South Africa up to Kenya. It is often referred to as a living fossil mainly because of its nearly unchanged morphology since the Middle Devonian. As it is a close relative to the last common ancestor of fish and tetrapods, molecular studies mostly focussed on their phylogenetic relationships. We now present a population genetic study based on 71 adults from the whole known range of the species. Despite an overall low genetic diversity, there is evidence for divergence of local populations. We assume that originally the coelacanths at the East African Coast derived from the Comoros population, but have since then diversified into additional independent populations: one in South Africa and another in Tanzania. Unexpectedly, we find a split of the Comoran coelacanths into two sympatric subpopulations. Despite its undeniably slow evolutionary rate, the coelacanth still diversifies and is therefore able to adapt to new environmental conditions. PMID- 22677283 TI - Developmental biology: a growing role for computer simulations. AB - Keeping cells separated in well-defined domains is essential for development. A new computational-experimental study elucidates the physical mechanisms that establish and maintain the dorsal-ventral compartment boundary in the Drosophila wing disc and demonstrates the increasing value of computer simulations in developmental biology. PMID- 22677284 TI - Taste: unraveling tomato flavor. AB - New research integrating genetics, chemistry and psychophysics has led to a model for tomato flavor intensity comprising sugars and acids plus six volatile molecules, providing a blueprint for improving the flavor of what has become an iconic symbol of the declining quality of fresh fruits and vegetables. PMID- 22677285 TI - Marine ecology: reserves do have a key role in fisheries. AB - A new study of the Great Barrier Reef proves a 100-year old conjecture correct: marine reserves do replenish populations in surrounding fishing grounds, while modern reserve networking theory is validated by exchange of offspring of animals among protected areas. PMID- 22677286 TI - Tubulogenesis: Src42A goes to great lengths in tube elongation. AB - New work shows the instructive role of Src42A kinase in tube size regulation. By inducing polarized cell-shape changes, Src42A promotes tube elongation in the Drosophila tracheal system. PMID- 22677287 TI - Tumour invasion: a new twist on Rac-driven mesenchymal migration. AB - Elongated mesenchymal migration of cancer cells is driven by Rac1 activation mediated by the adaptor NEDD9 and the exchange factor DOCK3. A new study reports a role for the transcription factor Twist1 in inducing mesenchymal migration by relieving the suppression of NEDD9 and DOCK3 by the microRNA let-7i. PMID- 22677288 TI - Population genomics: how bacterial species form and why they don't exist. AB - Two processes suggested to drive bacterial speciation - periodic selection and recombination - are generally thought to be mutually opposed. Recent work shows that data taken as evidence supporting the former may be explained by the latter, raising further problems for the idea of bacterial 'species'. PMID- 22677289 TI - Epithelial homeostasis: elimination by live cell extrusion. AB - To maintain a functional and harmonious epithelial society, the number and quality of cells need to be tightly controlled. Two recent studies reveal a novel cellular process for epithelial homeostasis: crowding-mediated live cell extrusion. PMID- 22677290 TI - Membrane biology: fission behind BARs. AB - Membrane bending is accomplished in part by amphipathic helix insertion into the bilayer and the assembly of BAR domain scaffolds preparing the membrane for fission. Two recent studies highlight the roles of amphipathic helices and BAR scaffolds in membrane fission and establish the structural basis of membrane bending by the N-BAR protein endophilin. PMID- 22677291 TI - Bistability, bifurcations, and Waddington's epigenetic landscape. AB - Waddington's epigenetic landscape is probably the most famous and most powerful metaphor in developmental biology. Cells, represented by balls, roll downhill through a landscape of bifurcating valleys. Each new valley represents a possible cell fate and the ridges between the valleys maintain the cell fate once it has been chosen. Here I examine models of two important developmental processes - cell-fate induction and lateral inhibition - and ask whether the landscapes for these models at least qualitatively resemble Waddington's picture. For cell-fate induction, the answer is no. The commitment of a cell to a new fate corresponds to the disappearance of a valley from the landscape, not the splitting of one valley into two, and it occurs through a type of bifurcation - a saddle-node bifurcation - that possesses an intrinsic irreversibility that is missing from Waddington's picture. Lateral inhibition, a symmetrical cell-cell competition process, corresponds better to Waddington's picture, with one valley reversibly splitting into two through a pitchfork bifurcation. I propose an alternative epigenetic landscape that has numerous valleys and ridges right from the start, with the process of cell-fate commitment corresponding to the irreversible disappearance of some of these valleys and ridges, via cell-fate induction, complemented by the creation of new valleys and ridges through processes like cell-cell competition. PMID- 22677293 TI - The structure of walking activity in people after stroke compared with older adults without disability: a cross-sectional study. AB - BACKGROUND: People with stroke have reduced walking activity. It is not known whether this deficit is due to a reduction in all aspects of walking activity or only in specific areas. Understanding specific walking activity deficits is necessary for the development of interventions that maximize improvements in activity after stroke. OBJECTIVE: The purpose of this study was to examine walking activity in people poststroke compared with older adults without disability. DESIGN: A cross-sectional study was conducted. METHODS: Fifty-four participants poststroke and 18 older adults without disability wore a step activity monitor for 3 days. The descriptors of walking activity calculated included steps per day (SPD), bouts per day (BPD), steps per bout (SPB), total time walking per day (TTW), percentage of time walking per day (PTW), and frequency of short, medium, and long walking bouts. RESULTS: Individuals classified as household and limited community ambulators (n=29) did not differ on any measure and were grouped (HHA-LCA group) for comparison with unlimited community ambulators (UCA group) (n=22) and with older adults without disability (n=14). The SPD, TTW, PTW, and BPD measurements were greatest in older adults and lowest in the HHA-LCA group. Seventy-two percent to 74% of all walking bouts were short, and this finding did not differ across groups. Walking in all categories (short, medium, and long) was lowest in the HHA-LCA group, greater in the UCA group, and greatest in older adults without disability. LIMITATIONS: Three days of walking activity were captured. CONCLUSIONS: The specific descriptors of walking activity presented provide insight into walking deficits after stroke that cannot be ascertained by looking at steps per day alone. The deficits that were revealed could be addressed through appropriate exercise prescription, underscoring the need to analyze the structure of walking activity. PMID- 22677294 TI - Assessment of the intraobserver and interobserver reliability of a communicating vessels volumeter to measure wrist-hand volume. AB - BACKGROUND: Traditional volumetry based on Archimedes' principle is the gold standard for the measurement of limb volume, but the routine use of this technique is discouraged because of several disadvantages. OBJECTIVE: The purpose of this study was to evaluate intraobserver and interobserver reliability of direct measurements of wrist-hand volume using a new communicating vessels volumeter based on Pascal's law. DESIGN: A reliability study was conducted. METHODS: To evaluate the reliability of the communicating vessels volumeter in generating measurements, 30 hands of 15 participants (9 women, 6 men) were measured 3 times each by 3 observers, totaling 270 volumetric results. RESULTS: Measurement time was short (X =3 minutes 42 seconds). The intraclass correlation coefficient (ICC) was .9977 for observer 1 and .9976 for observers 2 and 3. The interobserver ICC was .9998. The standard error of measurement was about 3 mL for all observers; the interobserver result was 1 mL. The interrater coefficient of variance (CV) was 1.15% for the series of 9 measurements collected for each segment; the intrarater CV was 1.20%. Limitations No swollen hands were measured, and measurements were not compared with the gold standard technique. Thus, accuracy of the new volumeter was not determined in this study. CONCLUSION: A new device has been developed for plethysmography of the extremities, and the results of its use to measure the volume of the wrist-hand segment were reliable in both intraobserver and interobserver analyses. PMID- 22677295 TI - Is the BESTest at its best? A suggested brief version based on interrater reliability, validity, internal consistency, and theoretical construct. AB - BACKGROUND: The Balance Evaluation Systems Test (BESTest) and Mini-BESTest are clinical examinations of balance impairment, but the tests are lengthy and the Mini-BESTest is theoretically inconsistent with the BESTest. OBJECTIVE: The purpose of this study was to generate an alternative version of the BESTest that is valid, reliable, time efficient, and founded upon the same theoretical underpinnings as the original test. DESIGN: This was a cross-sectional study. METHODS: Three raters evaluated 20 people with and without a neurological diagnosis. Test items with the highest item-section correlations defined the new Brief-BESTest. The validity of the BESTest, the Mini-BESTest, and the new Brief BESTest to identify people with or without a neurological diagnosis was compared. Interrater reliability of the test versions was evaluated by intraclass correlation coefficients. Validity was further investigated by determining the ability of each version of the examination to identify the fall status of a second cohort of 26 people with and without multiple sclerosis. RESULTS: Items of hip abductor strength, functional reach, one-leg stance, lateral push-and release, standing on foam with eyes closed, and the Timed "Up & Go" Test defined the Brief-BESTest. Intraclass correlation coefficients for all examination versions were greater than .98. The accuracy of identifying people from the first cohort with or without a neurological diagnosis was 78% for the BESTest versus 72% for the Mini-BESTest or Brief-BESTest. The sensitivity to fallers from the second cohort was 100% for the Brief-BESTest, 71% for the Mini-BESTest, and 86% for the BESTest, and all versions exhibited specificity of 95% to 100% to identify nonfallers. Limitations Further testing is needed to improve the generalizability of findings. CONCLUSIONS: Although preliminary, the Brief BESTest demonstrated reliability comparable to that of the Mini-BESTest and potentially superior sensitivity while requiring half the items of the Mini BESTest and representing all theoretically based sections of the original BESTest. PMID- 22677296 TI - Huwe1: a possible role in PD. PMID- 22677297 TI - Combined procedure of vascularized bone marrow transplantation and mesenchymal stem cells graft - an effective solution for rapid hematopoietic reconstitution and prevention of graft-versus-host disease. AB - Hematopoietic stem cell transplantation (HSCT) is a a standard therapeutic option for several diseases. The success of the procedure depends on quality and quantity of transplanted cells and on stromal capacity to create an optimal microenvironment, that supports survival and development of the hematopoietic elements. Conditions associated with stromal dysfunction lead to slower/insufficient engraftment and/or immune reconstitution. A possible solution to this problem is to realize a combined graft of hematopoietic stem cells along with the medular stroma in the form of vascularized bone marrow transplant (VBMT). Another major drawback of HSCT is the risk of graft versus host disease (GVHD). Recently, mesenchymal stromal cells (MSC) have demonstrated the capacity to down-regulate alloreactive T-cell and to enhance the engraftment. Cotransplantation of MSC could be a therapeutic option for a better engraftment and GVHD prevention. PMID- 22677299 TI - Idiopathic granulomatous mastitis: a report of twenty cases. AB - INTRODUCTION: Idiopathic granulomatous mastitis is a benign lesion of the mammary gland characterised by the presence of non-infectious inflammatory breast lesions limited to the lobules. OBJECTIVE: We report twenty cases of idiopathic granulomatous mastitis (IGM) with a discussion of epidemiology, clinical and diagnostic features, treatment and progress of this pathological entity. MATERIALS AND METHODS: A retrospective study of twenty cases compiled from a ten year period, from 952 pathological anatomy examinations carried out to investigate various breast pathologies. RESULTS: The patients had a mean age of 45.5 years. Clinical examinations revealed a tumefaction measuring between 2.5 and 18 cm in diameter. The mean size was 5.5 cm. Mammography showed nodular lesions and sonography demonstrated hypoechoic nodules. On histological examination there was a granulomatous inflammatory infiltrate of epithelioid and giant cells, without caseation necrosis, made up of lymphocytes, plasma cells and neutrophils. Microbiology investigations were negative. Lesion involvement was principally lobulocentric. Surgical excision of the lesions was combined with corticosteroid therapy in twelve cases, with non-steroidal anti-inflammatory drugs in another four and with antibiotic therapy in four cases. The patients made good progress in the short-term. DISCUSSION AND CONCLUSION: IGM is a rare entity. It poses a problem of differential diagnosis because it clinically resembles other forms of mastitis. The diagnosis can be made with certainty on histological studies. The treatment is medical alongside surgical excision. The prognosis of this disease remains favourable. PMID- 22677298 TI - Neuroprotective and neurogenesis agent for treating bipolar II disorder: add-on memantine to mood stabilizer works. AB - Bipolar disorder, characterized by a dysregulation of mood, impulsivity, risky behavior and interpersonal problems, is a recurrent and often becomes chronic psychiatric illness. However, bipolar subtypes are not often recognized in psychiatric settings, especially bipolar II subtype, until Akiskal and Angst made clear definition to bipolar I (BP-I) and bipolar II (BP-II) disorder in 1999. More and more studies, not only on family inheritance, diagnosis, but also on disease process have been reported that BP-I and BP-II are two different disorders with distinct pathological mechanisms. In general, patients with BP-II express less symptoms and have shorter hypomania stages than BP-I. According to a longitudinal research, patients with BP-II have poor recovery than do BP-I patients. Memantine used to be recognized as a noncompetitive N-methyl-d aspartate receptor antagonist. However, it was found to have neuroprotective and neurogenesis effect in several neurodegenerative diseases in the past years. We found that memantine could inhibit brain inflammatory response through its action on neuroglial cells and provide neurotrophic effect. The above evidences of benefit on auto-immune system with memantine would support that memantine as add on therapy to valproate might be more effective than valproate alone on improvement of the neuron degeneration in bipolar disorders. Review articles indicate that not only the mood stabilizers provide with good neuroprotection, but the memantine also have conspicuous anti-autoimmune and neurogenesis effect. Therefore, we propose that drugs with neuroprotective effect and neurotrophic effect may treat neurodegenerative diseases including BP-II. The combination treatment of mood stabilizers memantine may not only augment and improve the remedy for bipolar disorders, but also repair the damaged neurons and neurogenesis through activation of astroglial cell and release of neurotrophic factors. PMID- 22677300 TI - Infections of the spinal column--spondylodiscitis. AB - Infectious spondylodiscitis is an infection of the intervertebral disc and the adjacent vertebral bodies due to the introduction of a pyogen, usually by the haematogenous route. Plain film radiography (which is usually normal in the early stages) shows blurring of the vertebral endplates and a loss of disc height that progresses quickly. MRI is the examination of choice, as it detects oedema within the trabecular bone very early, before the onset of destruction. Injection of a contrast medium with fat signal saturation improves detection and visualisation of the spread of infection in the soft tissue and epidural space. Imaging can also be used to guide a needle aspiration to investigate the infective agent. PMID- 22677301 TI - Brain infections. AB - Brain infections are relatively rare, but they are potentially serious and have a poor prognosis. The cornerstone of the diagnosis is cerebrospinal fluid (CSF) analysis. Imaging is not systematic, but the indications of imaging are broad, particularly when faced with suspected focal damage, depending on the characteristics of the patient (child, immunosuppressed patient, geographic origin, etc.). It is based on MRI, which allows for aetiological diagnosis and an extension evaluation. In addition, in a certain number of cases, the type of infection is not known and it is up to the MRI via use of an exhaustive technique to diagnose an infectious origin when faced with a mass syndrome. This technical mastery, associated with knowledge of major brain infections, their method of contamination and their particular appearance on the MRI, should make it possible for the radiologist to fulfill his or her diagnostic role. PMID- 22677302 TI - Pharmacokinetics of a new diclofenac sodium formulation developed for subcutaneous and intramuscular administration. AB - OBJECTIVE: To assess the relative bioavailability of diclofenac sodium hydroxypropyl beta-cyclodextrin (HPbetaCD) administered via the subcutaneous (s.c.) and intramuscular (i.m.) route versus Voltaren(r) i.m. and to evaluate the dose linearity and pharmacokinetics of the s.c. formulation at three dose levels. Safety and local tolerability were also assessed. MATERIALS AND METHODS: One single-dose, randomized, three-way, crossover relative bioavailability study and one linearity single escalating dose, randomized, three-way cross-over pharmacokinetic study were conducted at two different clinical sites. A total of 42 healthy male and female subjects participated in both studies. Subjects received 75 mg/ml diclofenac sodium HPbetaCD (i.m. and s.c.) and Voltaren(r) 75 mg/3 ml (i.m.) in Study 1 and 25, 50, or 75 mg/ml diclofenac sodium HPbetaCD (s.c.) in Study 2. RESULTS: Study 1 demonstrated bioequivalence of the s.c. test formulation with Voltaren(r) i.m. with respect to Cmax and AUC. Bioequivalence of the test i.m. with Voltaren(r) i.m. was also demonstrated (except the upper limit of the 90% confidence interval (CI) for Cmax which marginally exceeded the 80 - 125% range (125.78%)). Study 2 demonstrated that after s.c. administration of the test formulation, both Cmax and AUC are linearly related to the tested diclofenac doses. All tested doses were safe and locally well-tolerated with no serious adverse events reported. CONCLUSION: Bioequivalence of diclofenac HPbetaCD 75 mg/ml after s.c. and i.m. administration with Voltaren(r) i.m. was demonstrated, except for the marginal deviation in Cmax when comparing the i.m. test and Voltaren(r). Linearity was also demonstrated for the three doses intended for marketing. PMID- 22677303 TI - Enhanced anticoagulant effect of warfarin in a patient treated with cloxacillin. AB - OBJECTIVE: To present the case of warfarin-cloxacillin interaction that resulted in an increased international normalized ratio (INR). CASE SUMMARY: A 70-year-old man had been treated with warfarin for atrial fibrillation. He was hospitalized because of superficial thrombophlebitis of the left median cubital vein, which developed after venipuncture. An antibiotic therapy with cloxacillin was initiated immediately after the admission. Two days later, INR value increased from baseline 1.9 to 4.6. Anticoagulation therapy was discontinued and INR value was measured daily. His INR remained high for the entire duration of antibiotic therapy. Three days after the cloxacillin therapy was discontinued, the INR decreased to the baseline value. DISCUSSION: In the presented case, the temporal relationship between the administration of cloxacillin and increased INR suggests that the cloxacillin was responsible for the enhanced warfarin activity. According to the Drug Interaction Probability Scale, a causal relationship between the warfarin-cloxacillin interaction and increased INR value was rated "probable". CONCLUSION: Interactions between warfarin and cloxacillin can result in serious adverse reactions. INR value should be closely monitored when patients are prescribed this combination of drugs. PMID- 22677304 TI - Low intrinsic drug activity and dominant vehicle (placebo) effect in the topical treatment of acne vulgaris. AB - In drug treatment for acne, topical products alone or in combination with systemic products are commonly prescribed. It was recently pointed out by Chiou that oral tetracyclines, the most commonly prescribed systemic drugs, may not be as effective as commonly assumed because the effect of placebo can approach drug effects during the 4 - 12 weeks of daily administration. The present work evaluated the percent contribution of vehicle (placebo) toward the reported efficacy of reduction in total (inflammatory and non-inflammatory) lesion counts of 8 commonly prescribed topical preparations at the end of 10 - 12 weeks of daily administration. These preparations included 0.1% tretinoin, 0.1% adapalene, 5% dapsone, 1% clindamycin, a combination of benzoyl peroxide with adapalene or clindamycin, and a clindamycin-tretinoin combination. The mean reduction from drugs and vehicles were 42 +/- 7.1%, and 23 +/- 5.0%, respectively; the mean contribution of vehicle toward drug effect was 55 +/- 15% (range 35 - 82%). For 5 benzoyl peroxide preparations evaluated (2 for 2.5%, and 3 for 5.0%), their respective means were 40 +/- 9%, and 25 +/- 15%, and vehicle-toward-drug contribution was 58 +/- 31% (range 9 - 89%). The present work shows the great importance of vehicle effects in topical therapy; in some cases this effect approached 90%. The potential significance of the above findings in the development of more effective topical anti-acne drugs was discussed. PMID- 22677305 TI - Diclofenac potassium 12.5 mg liquid capsules: earlier and higher exposure to diclofenac. A fasted, single-dose, comparative, bioavailability study versus diclofenac potassium 12.5 mg tablets. AB - BACKGROUND: A fast-release liquid capsule formulation of low-dose diclofenac- K is available, which aims to improve patient convenience and compliance. The new formulation is a soft gelatin capsule designed to facilitate faster absorption of diclofenac versus the tablet form with anticipated overall comparable bioavailability. OBJECTIVES: To compare the bioavailability of diclofenac-K 2 * 12.5 mg liquid capsules versus diclofenac- K 2 * 12.5 mg tablets. DESIGN: This randomized, open-label crossover, single-dose study was conducted in 42 healthy subjects (mean age 23.5 years) given diclofenac-K 2 * 12.5 mg liquid capsules or tablets over two 1-day treatment periods separated by a 14-day washout period. RESULTS: Diclofenac-K 12.5 mg liquid capsules were equivalent to the tablets in terms of total systemic exposure (mean AUCt ratio = 112%, 2-sided 90% CI = (107%, 116%)). However, the mean Cmax for the liquid capsules (1,090 ng/ml) was almost double that of the tablets (583 ng/ml) (mean Cmax ratio = 196%, 2-sided 90% CI = (169%, 227%)). Median tmax was ~ 10 min faster with the liquid capsules (0.42 h) compared with the tablets (0.58 h) and AUCtmax ref for the liquid capsules (294 ng*h/ml) was almost double the value for the tablets (158 ng*h/ml). This indicated a faster absorption of diclofenac from the liquid capsules compared to the tablet. There were no differences between the two treatments regarding safety, and both drugs were well tolerated. CONCLUSIONS: This study demonstrated equivalent overall systemic exposure to diclofenac but a faster absorption and substantially greater early exposure to diclofenac from diclofenac-K liquid capsules compared with the tablets, which may lead to a more rapid analgesic effect in patients. PMID- 22677306 TI - Diclofenac potassium 25 mg liquid capsules: earlier and higher exposure to diclofenac. A fasted, single-dose, comparative bioavailability study vs. diclofenac potassium 2 x 12.5 mg tablets. AB - BACKGROUND: A new liquid capsule formulation of low-dose diclofenac-K in 12.5 mg and 25 mg dosages has been developed to provide the patient with an easier to swallow form than the current low-dose tablets. The new formulation is expected to have a faster rate of absorption and comparable overall bioavailability compared with the tablet formulations. OBJECTIVES: To compare the systemic bioavailability of diclofenac from the new 25 mg liquid capsule vs. the currently registered diclofenac-K 2 * 12.5 mg tablets, and to evaluate the safety of the 25 mg liquid capsule. DESIGN: In this randomized, open-label, crossover, comparative bioavailability study, 42 healthy subjects (mean age 23.2 years) were given a single dose of diclofenac-K 25 mg liquid capsule or 2 * 12.5 mg tablets over 1 day treatment periods, separated by a washout period of 14 days. RESULTS: The total systemic exposure to diclofenac, as measured by the mean AUCs, was equivalent between treatments. However, the geometric mean Cmax for the 25 mg liquid capsule was almost double that of 2 * 12.5 mg tablets (1,058.2 vs. 564.5 ng/ml), while the median tmax was 5 minutes faster with the 25 mg liquid capsule and the geometric mean AUCtmax ref for the 25 mg liquid capsule (133.0 ng*h/ml) was much higher than for 2 * 12.5 mg tablets (91.6 ng*h/ml). The estimated AUCtmax ref ratio of 25 mg liquid capsule to 2 * 12.5 mg tablets was 143.1%, indicating much higher early exposure to diclofenac from the 25 mg liquid capsule. Both formulations were very well tolerated and only one adverse event was considered drug related (headache after taking the diclofenac-K 25 mg liquid capsule). CONCLUSIONS: Diclofenac-K 25 mg liquid capsule was equivalent to diclofenac-K 2 * 12.5 mg tablets in terms of overall systemic exposure to diclofenac. However, the rate of absorption of diclofenac was much faster from the liquid capsule than from the tablets, with a much greater early exposure to diclofenac. Both formulations were very well tolerated. PMID- 22677307 TI - Comparative pharmacokinetic and bioequivalence study of azithromycin 500 mg tablet in healthy Bangladeshi volunteers. AB - OBJECTIVE: Although several generic oral formulations of azithromycin (AZT; CAS 83905-01-5) are available in Bangladesh, information regarding the bioavailability of these formulations in the Bangladeshi population is unavailable. The purpose of this study was to compare the relative bioavailability and other pharmacokinetic properties of 2 formulations of AZT 500 mg tablet, namely Azomac(r) (General Pharmaceutical Ltd., Bangladesh) (Test formulation) and Zithromax(r) (Pfizer, Rome, Italy) (Reference product) and to evaluate whether these formulations meet the FDA criteria to assume bioequivalence in Bangladeshi volunteers. MATERIALS AND METHODS: A randomized, single-dose, two-way, cross-over, open-label pharmacokinetic study was performed in 24 healthy volunteers after administration of single dose of AZT 500 mg tablet under fasting condition following a washout period of 3 weeks. Blood samples were collected at pre-determined time points and analyzed for serum AZT concentration using a validated liquid chromatography-tandem mass spectrometry method. The pharmacokinetic parameters were determined by a noncompartmental method. RESULTS: From serum data, the obtained values given as mean (SD) for test and reference products were 382.41 (21.96), 392.31 (18.77) ng/ml for Cmax; 4.83(1.03), 4.83(1.03) h for tmax; 5,646.29 (912.19), 6,293.30 (966.76) h*ng/ml for AUC0-120; and 6,307.50 (863.40), 7,022.54 (961.28) h*ng/ml for AUC0-infinity, respectively. The mean t1/2 was 41.44 (7.01), 41.16 (6.38) h for Test formulation and Reference product, respectively. The analysis of variance revealed no period or sequence effect for any pharmacokinetic property; however, a significant formulation effect was observed for Cmax, AUC0-120, AUC0-infinity and AUMC0-120. The 90% confidence intervals of the test/ reference mean ratios of the ln-transformed Cmax, AUC0-120 and AUC0-infinity were 87.89 - 89.36%, 87.40 - 91.70% and 87.47 - 92.07%, respectively, which fell within the predetermined FDA bioequivalence range. CONCLUSION: It can be concluded that the test formulation met the regulatory criteria for bioequivalence to the Reference tablet formulation in terms of both rate and extent of absorption. PMID- 22677308 TI - COBRA Workshop on Biological and Chemical Information Technologies (BioChemIT), European Conference on Artificial Life, Paris, France, August 8 2011. Editorial. PMID- 22677309 TI - Fractional-order time series models for extracting the haemodynamic response from functional magnetic resonance imaging data. AB - The postprocessing of functional magnetic resonance imaging (fMRI) data to study the brain functions deals mainly with two objectives: signal detection and extraction of the haemodynamic response. Signal detection consists of exploring and detecting those areas of the brain that are triggered due to an external stimulus. Extraction of the haemodynamic response deals with describing and measuring the physiological process of activated regions in the brain due to stimulus. The haemodynamic response represents the change in oxygen levels since the brain functions require more glucose and oxygen upon stimulus that implies a change in blood flow. In the literature, different approaches to estimate and model the haemodynamic response have been proposed. These approaches can be discriminated in model structures that either provide a proper representation of the obtained measurements but provide no or a limited amount of physiological information, or provide physiological insight but lacks a proper fit to the data. In this paper, a novel model structure is studied for describing the haemodynamics in fMRI measurements: fractional models. We show that these models are flexible enough to describe the gathered data with the additional merit of providing physiological information. PMID- 22677310 TI - Multivariate multilinear regression. AB - Conventional regression methods, such as multivariate linear regression (MLR) and its extension principal component regression (PCR), deal well with the situations that the data are of the form of low-dimensional vector. When the dimension grows higher, it leads to the under sample problem (USP): the dimensionality of the feature space is much higher than the number of training samples. However, little attention has been paid to such a problem. This paper first adopts an in-depth investigation to the USP in PCR, which answers three questions: 1) Why is USP produced? 2) What is the condition for USP, and 3) How is the influence of USP on regression. With the help of the above analysis, the principal components selection problem of PCR is presented. Subsequently, to address the problem of PCR, a multivariate multilinear regression (MMR) model is proposed which gives a substitutive solution to MLR, under the condition of multilinear objects. The basic idea of MMR is to transfer the multilinear structure of objects into the regression coefficients as a constraint. As a result, the regression problem is reduced to find two low-dimensional coefficients so that the principal components selection problem is avoided. Moreover, the sample size needed for solving MMR is greatly reduced so that USP is alleviated. As there is no closed-form solution for MMR, an alternative projection procedure is designed to obtain the regression matrices. For the sake of completeness, the analysis of computational cost and the proof of convergence are studied subsequently. Furthermore, MMR is applied to model the fitting procedure in the active appearance model (AAM). Experiments are conducted on both the carefully designed synthesizing data set and AAM fitting databases verified the theoretical analysis. PMID- 22677311 TI - Obstetric outcome and long-term follow up of children conceived through assisted reproduction. AB - Most children born after assisted reproduction techniques are healthy. The most important risk associated with in-vitro fertilisation is the higher multiple birth rate, which may result in increased child morbidity because several embryos are transferred at each cycle. Single-embryo transfer reduces this risk dramatically. Large registry studies and meta-analyses have indicated a small but statistically significantly increased risk of congenital malformations among children born after in-vitro fertilisation. Other risks, such as preterm birth and low birth weight seem to be associated more with parental characteristics than the in-vitro fertilisation technique. All knowledge about children conceived through in-vitro fertilisation is based on observational studies, with risks of bias and confounders. It is possible that pregnancies and children resulting from in-vitro fertilisation are more carefully monitored and seek health care more frequently, resulting in more health problems being discovered. Continuous follow up of children after in-vitro fertilisation is of great importance, particularly as new techniques are constantly being introduced. PMID- 22677314 TI - Xanthine oxidase inhibitory activity of constituents of Cinnamomum cassia twigs. AB - A methanol extract of the twigs of Cinnamomum cassia was found to inhibit xanthine oxidase. Purification of the methanol extract afforded three new phenolic glycosides, cinnacasolide A-C (11-13), together with 10 known compounds (1-10). The structures of the three new compounds were determined by interpretation of spectroscopic data. Cinnamaldehyde derivatives 1-5 and 7 were significant inhibitors of xanthine oxidase, with IC(50) values ranging from 7.8 to 36.3 MUg/mL. The results indicate that the acyl group of these cinnamaldehyde derivatives plays an important role in the inhibition of xanthine oxidase. PMID- 22677313 TI - Iotrochamides A and B, antitrypanosomal compounds from the Australian marine sponge Iotrochota sp. AB - Bioassay-guided isolation of the CH(2)Cl(2)/MeOH extract from the Australian sponge Iotrochota sp. resulted in the purification of two new N-cinnamoyl-amino acids, iotrochamides A (1) and B (2). The chemical structures of 1 and 2 were determined by 1D/2D NMR and MS data analyses. Compounds 1 and 2 were shown to inhibit Trypanosoma brucei brucei with IC(50) values of 3.4 and 4.7 MUM, respectively. PMID- 22677312 TI - Haloenol pyranones and morpholinones as antineoplastic agents of prostate cancer. AB - Haloenol pyran-2-ones and morpholin-2-ones were synthesized and evaluated as inhibitors of cell growth in two different prostate human cancer cell lines (PC-3 and LNCaP). Analogs derived from L- and D-phenylglycine were found to be the most effective antagonists of LNCaP and PC-3 cell growth. Additional studies reveal that the inhibitors induced G2/M arrest and the (S)-enantiomer of the phenylglycine-based derivatives was a more potent inhibitor of cytosolic iPLA(2)beta. PMID- 22677315 TI - Synthesis of photolabile transcription initiators and preparation of photocleavable functional RNA by transcription. AB - Two new photolabile adenosine-containing transcription initiators with terminal thiol and amino functionalities are chemically synthesized. Transcription in the presence of the transcription initiators under the T7 phi2.5 promoter produces 5' thiol- and amino-functionalized RNA conjugated by a photocleavable (PC) linker. Further RNA functionalization with biotin may be achieved through acyl transfer reactions from either biotinyl AMP to the RNA thiol group or biotin NHS to the RNA amino group. Photocleavage of the PC linker displays relatively fast kinetics with a half-life of 4-5 min. The availability of these transcription initiators makes new photolabile RNA accessible for affinity purification of RNA, in vitro selection of functional RNAs, and functional RNA caging. PMID- 22677316 TI - Identification of spirocyclic piperidine-azetidine inverse agonists of the ghrelin receptor. AB - The discovery of spirocyclic piperidine-azetidine inverse agonists of the ghrelin receptor is described. The characterization and redressing of the issues associated with these compounds is detailed. An efficient three-step synthesis and a binding assay were relied upon as the primary means of rapidly improving potency and ADMET properties for this class of inverse agonist compounds. Compound 10 n bearing distributed polarity in the form of an imidazo-thiazole acetamide and a phenyl triazole is a unit lower in logP and has significantly improved binding affinity compared to the hit molecule 10a, providing support for further optimization of this series of compounds. PMID- 22677317 TI - Symmetrical approach of spiro-pyrazolidinediones as acetyl-CoA carboxylase inhibitors. AB - Spiro-pyrazolidinedione derivatives without quaternary chiral center were discovered by structure-based drug design and characterized as potent acetyl-CoA carboxylase (ACC) inhibitors. The high metabolic stability of the spiro pyrazolo[1,2-a]pyridazine scaffold and enhancement of the activity by incorporation of a 7-methoxy group on the benzothiophene core successfully led to the identification of compound 4c as an orally bioavailable and highly potent ACC inhibitor. Oral administration of 4c significantly decreased the values of the respiratory quotient in rats, indicating the stimulation of fatty acid oxidation. PMID- 22677318 TI - Synthesis of pacidamycin analogues via an Ugi-multicomponent reaction. AB - The second-generation synthesis of 3'-hydroxypacidamycin D (2) has been accomplished via an Ugi-four component reaction at a late stage of the synthesis. This approach provided ready access to a range of analogues including diastereomers of the diaminobutylic acid residue and hybrid-type analogues of mureidomycins. Biological evaluations of these analogues indicated that the stereochemistry at the diaminobutylic acid residue has a crucial impact on both the MraY biochemical inhibition and whole-cell antibacterial activity. PMID- 22677319 TI - Hit-to-lead investigation of a series of novel combined dopamine D2 and muscarinic M1 receptor ligands with putative antipsychotic and pro-cognitive potential. AB - We describe the discovery of a series of compounds based on 1-{3-[4-(2-oxo-2,3 dihydro-benzoimidazol-1-yl)-piperidin-1-yl]-propyl}-3,4-dihydro-1H-quinolin-2-one (3), showing combined D(2) receptor affinity and M(1) receptor agonism. Based on a strategy of controlling logP, we herein describe a hit-to-lead investigation with the aim of retaining the combined D(2)/M(1) profile, while removing the propensity of the compounds to inhibit the hERG channel, as well as at obtaining acceptable pharmacokinetic properties. Although a SAR was evident for all four parameters in question, it was not possible to separate hERG channel inhibition and D(2) receptor affinity by this effort; whilst it was feasible to obtain compounds with M(1) receptor agonism, acceptable clearance, and weak hERG inhibition. PMID- 22677320 TI - Synthesis, biological evaluation of 5-carbomethoxymethyl-7-hydroxy-2 pentylchromone, 5-carboethoxymethyl-4',7-dihydroxyflavone and their analogues. AB - In this letter, we describe the first synthesis of two recently isolated flavones 5-carbomethoxymethyl-7-hydroxy-2-pentylchromone (3a), 5-carboethoxymethyl-4',7 dihydroxyflavone (3b) and their derivatives (3c-t), evaluated for their antimicrobial, antioxidant and anticancer activities. Most of the synthesized compounds exhibited antimicrobial activity against the tested microbial strains and some of these compounds were found to be more potent as compared to the standard drugs like neomycin and luteolin. Interestingly, some of these synthesized compounds also showed moderate antioxidant property. PMID- 22677321 TI - Monitoring kinematic changes with fatigue in running using body-worn sensors. AB - In this paper, we investigate monitoring of kinematic changes evoked by fatigue in running using wearable technology. Movement data were recorded with ETHOS devices. ETHOS is the ETH Orientation Sensor, a customized inertial measurement unit for unconstrained monitoring of human movement. We perform two real-world experiments, in which 21 runners of different skill levels participated. The real world experiments capture two exhausting 45-min runs: one on a treadmill and one on a conventional outdoor track. We describe and evaluate algorithms to extract kinematic parameters from the sensor data. We identified parameters that change with fatigue for all runners, ones that change for runners of distinct skill levels, and ones that are dependent on an individual's running technique. Overall, we found that observations from treadmill running are not always generalizable to outdoor running. We, thus, argue for using wearable technology to provide athletes and trainers with continuous, quantitative objective measurements of running technique. These could be used to further gain insight into the complex relationship of running kinematics, injury risk, fatigue, and running economy. PMID- 22677322 TI - Data interoperability and multimedia content management in e-Health systems. AB - E-Health systems provide a collaborative platform for sharing patients medical data typically stored in distributed autonomous healthcare data sources. Each autonomous source stores its medical and multimedia data without following any global structure. This causes heterogeneity in the underlying sources with respect to the data and storage structure. Therefore, a data interoperability mechanism is required for sharing the data among the heterogeneous sources. A proper metadata structure is also necessary to represent multimedia content in the sources to enable efficient query processing. Considering these needs, we present an interoperability solution for sharing data among heterogeneous data sources. We also propose a metadata management framework for medical multimedia con-tent including X-ray, ECG, MRI, and ultrasound images. The framework identifies features, generates and represents metadata, and produces identifiers for the medical multimedia content to facilitate efficient query processing. The framework has been tested with various user queries and the accuracy of the query results evaluated by means of precision, recall, and user feedback methods. The results confirm the effectiveness of the proposed approach. PMID- 22677323 TI - Mechanism of entomotoxicity of the plant lectin from Hippeastrum hybrid (Amaryllis) in Spodoptera littoralis larvae. AB - Plant lectins have received a lot of attention because of their insecticidal properties. When orally administered in artificial diet or in transgenic plants, lectins provoke a wide range of detrimental effects, including alteration of the digestive enzyme machinery, fecundity drop, reduced feeding, changes in oviposition behavior, growth and development inhibition and mortality. Although many studies reported the entomotoxicity of lectins, only a few of them investigated the mode of action by which lectins exert toxicity. In the present paper we have studied for the first time the insecticidal potential of the plant lectin from Hippeastrum hybrid (Amaryllis) (HHA) bulbs against the larvae of the cotton leafworm (Spodoptera littoralis). Bioassays on neonate larvae showed that this mannose-specific lectin affected larval growth, causing a development retardation and larval weight decrease. Using primary cell cultures from S. littoralis midguts and confocal microscopy we have elucidated FITC-HHA binding and internalization mechanisms. We found that HHA did not exert a toxic effect on S. littoralis midgut cells, but HHA interaction with the brush border of midgut cells interfered with normal nutrient absorption in the S. littoralis midgut, thereby affecting normal larval growth in vivo. This study thus confirms the potential of mannose-specific lectins as pest control agents and sheds light on the mechanism underlying lectin entomotoxicity. PMID- 22677324 TI - Bilateral vertebral artery dissection and essential thrombocythemia with JAK2 mutation. PMID- 22677325 TI - Diagnostic strategy for limb-girdle muscular dystrophies. AB - Limb-girdle muscular dystrophies represent a major chapter of genetic myopathies. Many different entities have been identified, most of them with recessive transmission, a minority with dominant heredity. Diagnostic strategy is presented, based on clinical analysis, muscle biopsy revealing in most cases a specific protein deficiency and gene screening, the golden standard, showing the deleterious mutations. Identification may be difficult due to the relatively poor specificity of the clinical and histological features and to the absence of specific protein deficiency and/or causative mutations. A comprehensive discussion of these difficult cases is proposed. PMID- 22677326 TI - [Focal convexal subarachnoid hemorrhage: clinical presentation, imaging patterns and etiologic findings in 23 patients]. AB - INTRODUCTION: Clinical presentation and etiology of localized nontraumatic convexal subarachnoid hemorrhage (cSAH) have been described in a few patients. They differ from those of aneurysmal subarachnoid bleeding which is diffuse. The purpose of this study was to describe the clinical presentation, the radiologic findings and causes of cSAH. METHODS: We selected patients admitted to the neurology department of CHU of Nimes or Montpellier, from May 2008 to May 2011, who presented with cSAH, observed in a single cortical sulcus unrelated to trauma and identified on brain MRI T2* weighted images as a hyposignal in one sulcus of the convexity. Data collection was retrospective. RESULTS: Twenty-three patients (14 men and nine women) were included. Mean age was 69.5years (range 29-86). Patients had mostly sensory or sensorimotor deficits which was regressive in less than 30minutes, recurrent, and seldom accompanied by headache. Brain MRI allowed the identification of patients with old brain hematomas (n=2), lobar microbleeds (n=7) and superficial cortical hemosiderosis (n=6). The etiologic diagnosis was determined in 43% (n=10/23): cerebral amyloid angiopathy (n=3), reversible cerebral vasoconstriction syndrome (n=2), primary cerebral angiitis (n=1), posterior reversible encephalopathy syndrome (n=1), cortical vein thrombosis (n=3, two of them associated with dural sinus thrombosis). Cerebral angiography was performed in 11 patients and gave the etiologic diagnosis (angiitis, cortical vein thrombosis) in two. Follow-up was available for 16 patients (mean 12months, range 3months to 5years). Etiology was established during follow-up in two patients, both had cerebral amyloid angiopathy diagnosed after recurrent lobar hematomas. CONCLUSIONS: cSAH has various causes, but clinical presentations appear to be relatively stereotyped with recurrent and brief episodes of sensorimotor deficits. A comprehensive assessment and monitoring would lead to an etiologic diagnosis in some patients. PMID- 22677327 TI - [Hyperprolactinemia and gynaecomastia induced by benserazide]. PMID- 22677328 TI - No difference in surgical outcomes between open and closed exposure of palatally displaced maxillary canines. AB - PURPOSE: To investigate differences in surgical outcomes between open and closed exposure for palatally displaced maxillary canines. MATERIALS AND METHODS: This multicenter randomized controlled trial involved 2 parallel groups. The settings were 1 dental teaching hospital in and 2 hospital units near Sheffield, UK. Participants were younger than 20 years, had a unilateral palatally displaced maxillary canine, and provided informed consent. They were randomly allocated to receive the open or the closed surgical procedure. The outcomes were time spent in the operating room and 10-day postoperative patient questionnaire findings. Statistical differences between the 2 techniques were tested using independent t tests for continuous variables and chi(2) tests for frequencies. RESULTS: The final study sample was composed of 71 participants (64% female). There were no differences in the gender ratios (open: 27 female, 13 male; closed; 25 female, 16 male) or mean ages (open: 14.3 yrs; standard deviation [SD], 1.3 yrs; closed: 14.1 yrs; SD, 1.6 yrs) of the 2 groups at the start. The mean operating times for the open and closed techniques were 34.3 minutes (SD, 11.2 min) and 34.3 minutes (SD, 11.9 min), respectively (P = .986). There were no statistically significant differences between the 2 treatment groups for any patient-assessed outcome (P > .05). CONCLUSIONS: There were no differences in the surgical outcomes investigated in this study between open and closed exposure for palatally displaced maxillary canines. PMID- 22677329 TI - Maxillary advancement with conventional orthognathic surgery in patients with cleft lip and palate: is it a stable technique? AB - PURPOSE: To evaluate the long-term skeletal stability after maxillary surgical advancement with conventional Le Fort I osteotomy in patients with cleft lip and palate by a systematic review of the published data. MATERIALS AND METHODS: Electronic databases, "gray literature," and reference list searches were conducted. The inclusion criteria were the stability of maxillary surgical advancement with conventional Le Fort I osteotomy fixed with plates and assessed at the post-treatment follow-up 1 year or more postoperatively in patients with cleft lip and/or palate. Full reports were retrieved from abstracts or titles that appeared to meet the inclusion criteria or lacked sufficient detail for immediate exclusion. Once full reports were collected, they were again reviewed, considering more detailed inclusion criteria for a final selection decision. A methodologic quality assessment tool was used. The quantity and quality of the obtained data precluded a meta-analytic approach. RESULTS: A total of 25 abstracts/titles met the initial search criteria, and 10 studies were finally selected. The overall methodologic quality scores were high for only 1 randomized clinical trial. After maxillary advancement with Le Fort I in patients with cleft lip and palate, the long-term horizontal relapse at the A-point was 20% to 30% in 4 studies and 30% to 40% in 3 studies. In addition, vertical relapse was more than 50% in 4 studies. The study judged as a high-quality study reported a 37% rate of horizontal relapse and a 65% rate of vertical relapse at the A-point. CONCLUSIONS: Current evidence suggests maxillary surgical advancement with conventional Le Fort I osteotomy in patients with cleft lip and palate appears to show a moderate relapse rate in the horizontal plane and a high relapse rate in the vertical plane. PMID- 22677330 TI - Parosteal osteoma arising in an iliac bone graft used for mandibular reconstruction. PMID- 22677331 TI - Oral and maxillofacial surgery residents have poor understanding of biostatistics. AB - PURPOSE: The purpose of this study was to evaluate residents' understanding of biostatistics and interpretation of research results. MATERIALS AND METHODS: A questionnaire previously used in internal medicine residents was modified to include oral and maxillofacial surgery (OMS) examples. The survey included sections to identify demographic and educational characteristics of residents, attitudes and confidence, and the primary outcome-knowledge of biostatistics. In 2009 an invitation to the Internet survey was sent to all 106 program directors in the United States, who were requested to forward it to their residents. RESULTS: One hundred twelve residents responded. The percentage of residents who had taken a course in epidemiology was 53%; biostatistics, 49%; and evidence based dentistry, 65%. Conversely, 10% of OMS residents had taken none of these classes. Across the 6-item test of knowledge of statistical methods, the mean percentage of correct answers was 38% (SD, 22%). Nearly half of the residents (42%) could not correctly identify continuous, ordinal, or nominal variables. Only 21% correctly identified a case-control study, but 79% correctly identified that the purpose of blinding was to reduce bias. Only 46% correctly interpreted a clinically unimportant and statistically nonsignificant result. None of the demographic or experience factors of OMS residents were related to statistical knowledge. Overall, OMS resident knowledge was below that of internal medicine residents (P<.0001). However, OMS residents were overconfident in their claim to understand most statistical terms. CONCLUSIONS: OMS residents lack knowledge in biostatistics and the interpretation of research and are thus unprepared to interpret the results of published clinical research. Residency programs should include effective biostatistical training in their curricula to prepare residents in evidence-based dentistry. PMID- 22677332 TI - Utility of a salivary biosensor for objective assessment of surgery-related stress. AB - PURPOSE: To evaluate the clinical utility of a salivary alpha-amylase (sAA) biosensor for assessing oral surgery-related stress responses and the differential effect of the personality trait of pain catastrophizing. PATIENTS AND METHODS: A prospective cohort study was conducted in 76 healthy subjects who underwent elective removal of their third molars. Along with subjects' self reports of anxiety and pain, biosensor-facilitated measurements of sAA levels were obtained at multiple time points during the preoperative consult, surgery, and postsurgical follow-up visits. In addition, subjects completed the Pain Catastrophizing Scale at baseline. Mixed-effect regression models examined changes in sAA levels and self-report ratings within and across visits and the contribution of pain catastrophizing. RESULTS: The sAA levels were lower during surgery and postsurgical follow-up compared with the consult visit (P < .01). The sAA levels decreased during the surgery visit (P < .05) and did not change during the consult or follow-up visits. Individuals who reported greater helplessness to pain manifested higher sAA levels during the surgery visit (P < .05). Self reported anxiety ratings were highest during the surgery visit, and pain ratings were highest during the follow-up visit. CONCLUSIONS: The sAA levels did not show the predicted increases during the surgery visit compared with the consult and postsurgical follow-up visits or increases during the surgery visit. However, individuals who reported responding to pain with helplessness had higher sAA levels in anticipation of surgery, providing proof of concept for the value of point-of-care assessments of surgery-induced stresses and the differential effect of personality traits. PMID- 22677334 TI - Quantitative phosphoproteomics to characterize signaling networks. AB - Reversible protein phosphorylation is involved in the regulation of most, if not all, major cellular processes via dynamic signal transduction pathways. During the last decade quantitative phosphoproteomics have evolved from a highly specialized area to a powerful and versatile platform for analyzing protein phosphorylation at a system-wide scale and has become the intuitive strategy for comprehensive characterization of signaling networks. Contemporary phosphoproteomics use highly optimized procedures for sample preparation, mass spectrometry and data analysis algorithms to identify and quantify thousands of phosphorylations, thus providing extensive overviews of the cellular signaling networks. As a result of these developments quantitative phosphoproteomics have been applied to study processes as diverse as immunology, stem cell biology and DNA damage. Here we review the developments in phosphoproteomics technology that have facilitated the application of phosphoproteomics to signaling networks and introduce examples of recent system-wide applications of quantitative phosphoproteomics. Despite the great advances in phosphoproteomics technology there are still several outstanding issues and we provide here our outlook on the current limitations and challenges in the field. PMID- 22677333 TI - Toward quantitative phosphotyrosine profiling in vivo. AB - Tyrosine phosphorylation is a dynamic reversible post-translational modification that regulates many aspects of cell biology. To understand how this modification controls biological function, it is necessary to not only identify the specific sites of phosphorylation, but also to quantify how phosphorylation levels on these sites may be altered under specific physiological conditions. Due to its sensitivity and accuracy, mass spectrometry (MS) has widely been applied to the identification and characterization of phosphotyrosine signaling across biological systems. In this review we highlight the advances in both MS and phosphotyrosine enrichment methods that have been developed to enable the identification of low level tyrosine phosphorylation events. Computational and manual approaches to ensure confident identification of phosphopeptide sequence and determination of phosphorylation site localization are discussed along with methods that have been applied to the relative quantification of large numbers of phosphorylation sites. Finally, we provide an overview of the challenges ahead as we extend these technologies to the characterization of tyrosine phosphorylation signaling in vivo. With these latest developments in analytical and computational techniques, it is now possible to derive biological insight from quantitative MS based analysis of signaling networks in vitro and in vivo. Application of these approaches to a wide variety of biological systems will define how signal transduction regulates cellular physiology in health and disease. PMID- 22677335 TI - Are titin properties reflected in single myofibrils? AB - Titin is a structural protein in muscle that spans the half sarcomere from Z-band to M-line. Although there are selected studies on titin's mechanical properties from tests on isolated molecules or titin fragments, little is known about its behavior within the structural confines of a sarcomere. Here, we tested the hypothesis that titin properties might be reflected well in single myofibrils. Single myofibrils from rabbit psoas were prepared for measurement of passive stretch-shortening cycles at lengths where passive titin forces occur. Three repeat stretch-shortening cycles with magnitudes between 1.0 and 3.0MUm/sarcomere were performed at a speed of 0.1MUm/s.sarcomere and repeated after a ten minute rest at zero force. These tests were performed in a relaxation solution (passive) and an activation solution (active) where cross-bridge attachment was inhibited with 2,3 butanedionemonoxime. Myofibrils behaved viscoelastically producing an increased efficiency with repeat stretch-shortening cycles, but a decreased efficiency with increasing stretch magnitudes. Furthermore, we observed a first distinct inflection point in the force-elongation curve at an average sarcomere length of 3.5MUm that was associated with an average force of 68+/-5nN/mm. This inflection point was thought to reflect the onset of Ig domain unfolding and was missing after a ten minute rest at zero force, suggesting a lack of spontaneous Ig domain refolding. These passive myofibrillar properties observed here are consistent with those observed in isolated titin molecules, suggesting that the mechanics of titin are well preserved in isolated myofibrils, and thus, can be studied readily in myofibrils, rather than in the extremely difficult and labile single titin preparations. PMID- 22677336 TI - Geometrical changes of knee ligaments and patellar tendon during passive flexion. AB - Patterns of fibre elongation and orientation for the cruciate and collateral ligaments of the human knee joint and for the patellar tendon have not yet been established in three-dimensions. These patterns are essential for understanding thoroughly the contribution of these soft tissues to joint function and of value in surgical treatments for a more conscious assessment of the knee status. Measurements from 10 normal cadaver knees are here reported using an accurate surgical navigation system and consistent anatomical references, over a large flexion arc, and according to current recommended conventions. The contours of relevant sub-bundles were digitised over the corresponding origins and insertions on the bones. Representative fibres were calculated as the straight line segments joining the centroids of these attachment areas. The most isometric fibre was also taken as that whose attachment points were at the minimum change in length over the flexion arc. Changes in length and orientation of these fibres were reported versus the flexion angle. A good general repeatability of intra- and inter-specimens was found. Isometric fibres were found in the locations reported in the literature. During knee flexion, ligament sub-bundles slacken in the anterior cruciate ligament, and in the medial and lateral collateral ligaments, whereas they tighten in the posterior cruciate ligament. In each cruciate ligament the two compounding sub-bundles have different extents for the change in fibre length, and also bend differently from each other on both tibial planes. In the collateral ligaments and patellar tendon all fibres bend posteriorly. Patellar tendon underwent complex changes in length and orientation, on both the tibial sagittal and frontal planes. For the first time thorough and consistent patterns of geometrical changes are provided for the main knee ligaments and tendons after careful fibre mapping. PMID- 22677337 TI - Numerical analysis of an osseointegrated prosthesis fixation with reduced bone failure risk and periprosthetic bone loss. AB - Currently available implants for direct attachment of prosthesis to the skeletal system after transfemoral amputation (OPRA system, Integrum AB, Sweden and ISP Endo/Exo prosthesis, ESKA Implants AG, Germany) show many advantages over the conventional socket fixation. However, restraining biomechanical issues such as considerable bone loss around the stem and peri-prosthetic bone fractures are present. To overcome these limiting issues a new concept of the direct intramedullary fixation was developed. We hypothesize that the new design will reduce the peri-prosthetic bone failure risk and adverse bone remodeling by restoring the natural load transfer in the femur. Generic CT-based finite element models of an intact femur and amputated bones implanted with 3 analyzed implants were created and loaded with a normal walking and a forward fall load. The strain adaptive bone remodeling theory was used to predict long-term bone changes around the implants and the periprosthetic bone failure risk was evaluated by the von Mises stress criterion. The results show that the new design provides close to physiological distribution of stresses in the bone and lower bone failure risk for the normal walking as compared to the OPRA and the ISP implants. The bone remodeling simulations did not reveal any overall bone loss around the new design, as opposed to the OPRA and the ISP implants, which induce considerable bone loss in the distal end of the femur. This positive outcome shows that the presented concept has a potential to considerably improve safety of the rehabilitation with the direct fixation implants. PMID- 22677338 TI - The effects of gait strategy on metabolic rate and indicators of stability during downhill walking. AB - When walking at a given speed, humans often appear to prefer gait patterns that minimize metabolic rate, thereby maximizing metabolic economy. However, recent experiments have demonstrated that humans do not maximize economy when walking downhill. The purpose of this study was to investigate whether this non metabolically optimal behavior is the result of a trade-off between metabolic economy and gait stability. We hypothesized that humans have the ability to modulate their gait strategy to increase either metabolic economy or stability, but that increase in one measure will be accompanied by decrease in the other. Subjects walked downhill using gait strategies ranging from risky to conservative, which were either prescribed by verbal instructions or induced by the threat of perturbations. We quantified spatiotemporal gait characteristics, metabolic rate and several indicators of stability previously associated with fall risk: stride period variability; step width variability; Lyapunov exponents; Floquet multipliers; and stride period fractal index. When subjects walked using conservative gait strategies, stride periods and lengths decreased, metabolic rate increased, and anteroposterior maximum Lyapunov exponents increased, which has previously been interpreted as an indicator of decreased stability. These results do not provide clear support for the proposed trade-off between economy and stability, particularly when stability is approximated using complex metrics. However, several gait pattern changes previously linked to increased fall risk were observed when our healthy subjects walked with a conservative strategy, suggesting that these changes may be a response to, rather than a cause of, increased fall risk. PMID- 22677339 TI - Single nucleotide polymorphisms in beta-tubulin selected in Onchocerca volvulus following repeated ivermectin treatment: possible indication of resistance selection. AB - The control of onchocerciasis or river blindness by mass treatment of the population with ivermectin (IVM) has been a great success until now, so that in certain foci its elimination has become feasible. However, after more than 20 years of repeated IVM mass treatment, the disease still persists in many endemic countries. Sub-optimal responses and genetic changes have been reported in Onchocerca volvulus populations under high IVM pressure but more work is needed to determine whether resistance is developing. The situation needs to be urgently clarified to preserve the achievements of onchocerciasis control programs. In this study, O. volvulus adult worms were collected from the same individuals, before IVM exposure and following three years of annual or three-monthly treatments at 150 MUg/kg or 800 MUg/kg. Four single nucleotide polymorphisms (SNPs) occurring in the beta-tubulin gene of these parasites were investigated. We found changes in genotype frequencies in O. volvulus beta-tubulin gene associated with IVM treatments. The SNP at position 1545 (A/G) showed a significant increase in frequency of the less common nucleotide in the female worms following treatment. After 13 three-monthly treatments, female worm homozygotes with the less common genotype, prior to treatment, increased in frequency. The selected homozygotes, as well as heterozygotes, appeared to be less fertile (without or with very few embryonic stages in their uteri) than the wild-type homozygotes. These results provide additional evidence for genetic selection and strengthen the warning that selection for IVM resistance may be occurring in some O. volvulus populations. PMID- 22677340 TI - Trichomonas vaginalis ribosomal RNA: identification and characterisation of the transcription promoter and terminator sequences. AB - Trichomonas vaginalis is a parasitic protozoan of both medical and biological relevance. Transcriptional studies in this organism have focused mainly on type II pol promoters, whereas the elements necessary for transcription by polI or polIII have not been investigated. Here, with the aid of a transient transcription system, we characterised the rDNA intergenic region, defining both the promoter and the terminator sequences required for transcription. We defined the promoter as a compact region of approximately 180 bp. We also identified a potential upstream control element (UCE) that was located 80 bp upstream of the transcription start point (TSP). A transcription termination element was identified within a 34 bp region that was located immediately downstream of the 28S coding sequence. The function of this element depends upon polarity and the presence of both a stretch of uridine residues (U's) and a hairpin structure in the transcript. Our observations provide a strong basis for the study of DNA recognition by the polI transcriptional machinery in this early divergent organism. PMID- 22677341 TI - To the editor: spatial incidence of dengue infections in Queensland, Australia. PMID- 22677342 TI - Maternal exposure to di-(2-ethylhexyl)phthalate alters kidney development through the renin-angiotensin system in offspring. AB - Di-(2-ethylhexyl)phthalate (DEHP) is a widely used industrial plasticizer to which humans are widely exposed. We investigated the consequences of maternal exposure to DEHP on nephron formation, examined the programming of renal function and blood pressure and explored the mechanism in offspring. Maternal rats were treated with vehicle, 0.25 and 6.25mg/kg body weight/day DEHP respectively from gestation day 0 to postnatal day 21. Maternal DEHP exposure resulted in lower number of nephrons, higher glomerular volume and smaller Bowman's capsule in the DEHP-treated offspring at weaning, as well as glomerulosclerosis, interstitial fibrosis and effacement of podocyte foot processes in adulthood. In the DEHP treated offspring, the renal function was lower and the blood pressure was higher. The renal protein expression of renin and angiotensin II was reduced at birth day and increased at weaning. Maternal DEHP exposure also led to reduced mRNA expression of some renal development involved genes at birth day, including Foxd1, Gdnf, Pax2 and Wnt11. While, the mRNA expression of some genes was raised, including Bmp4, Cdh11, Calm1 and Ywhab. These data show that maternal DEHP exposure impairs the offspring renal development, resulting in a nephron deficit, and subsequently elevated blood pressure later in life. Our findings suggest that DEHP exposure in developmental periods may affect the development of nephrons and adult renal disease through inhibition of the renin-angiotensin system. PMID- 22677343 TI - Acute effects of exposure to vapors of hydrogen peroxide in humans. AB - Hydrogen peroxide is a reactive chemical mainly used for bleaching, as a disinfectant, and as a general oxidizing agent. The aim of this study was to investigate subtle acute effects of inhaled hydrogen peroxide vapors. Eleven healthy volunteers were exposed to 0 (clean air), 0.5 and 2.2 ppm for 2h at rest. Symptoms related to irritation and central nervous system effects were rated with Visual Analog Scales. The ratings varied considerably but were generally low and with no significant differences between exposure conditions, although the ratings of smell (p=0.09, Friedman's test), nasal irritation (p=0.06) and throat irritation (p=0.06) showed borderline tendencies to increase at 2.2 but not at 0 and 0.5 ppm. Nasal airway resistance increased after exposure to 2.2 ppm hydrogen peroxide (p=0.04, paired t-test) but not after 0.5 ppm. No exposure-related effects on pulmonary function, nasal swelling, breathing frequency and blinking frequency were detected. Furthermore, no clear effects were seen on markers of inflammation and coagulation (interleukin-6, C-reactive protein, serum amyloid A, fibrinogen, factor VIII, von Willebrand factor and Clara cell protein in plasma). In conclusion, our study suggests that hydrogen peroxide is slightly irritating at 2.2 ppm, but not at 0.5 ppm. PMID- 22677344 TI - Using population physiologically based pharmacokinetic modeling to determine optimal sampling times and to interpret biological exposure markers: The example of occupational exposure to styrene. AB - BACKGROUND: Biomonitoring of chemicals in the workplace provides an integrated characterization of exposure that accounts for uptake through multiple pathways and physiological parameters influencing the toxicokinetics. OBJECTIVES: We used the case of styrene to (i) determine the best times to sample venous blood and end-exhaled air, (ii) characterize the inter-individual variability in biological levels following occupational exposure and (iii) propose biological limit values using a population physiologically based pharmacokinetic (PBPK) model. METHODS: We performed Monte Carlo simulations with various physiological, exposure and workload scenarios. Optimal sampling times were identified through regression analyses between levels in biological samples and 24-h area under the arterial blood concentration vs. time curve. We characterized the variability in levels of styrene in biological samples for exposures to a time weighted average (TWA) of 20ppm. RESULTS: Simulations suggest that the best times to sample venous blood are at the end of shift in poorly ventilated workplaces and 15min after the shift in highly ventilated workplaces. Exhaled air samples are most informative 15min after the shift. For a light workload, simulated styrene levels have a median (5th-95th percentiles) of 0.4mg/l (0.2-0.6) in venous blood at the end of shift and 0.5ppm (0.3-0.8) in exhaled air 15min after the end of shift. CONCLUSION: This study supports the current BEI((r)) of the ACGIH of 0.2mg/l of styrene in venous blood at the end of shift and indicates a biological limit value of 0.3ppm in end-exhaled air 15min after the end of shift. PMID- 22677345 TI - Cadmium activates a programmed, lysosomal membrane permeabilization-dependent necrosis pathway. AB - Cadmium is a highly toxic, carcinogenic, and atherogenic element. A central principle in many Cd-induced pathophysiologies is the induction of cell death. In past studies Cd was shown to cause apoptosis, necrosis, programmed necrosis, or autophagy. This study was conducted to precisely define the end stage processes and outcome of Cd-induced cell death in endothelial cells (ECs). We show that Cd leads to acidification and permeabilization of lysosomes, followed by the release of active DNAse II from lysosomes. The absence of nuclear DNA due to DNAse II activity may have lead to misinterpretations of the type of cell death outcome in previous studies. Further, Cd-induced cell death is characterized by a massive release of lactate dehydrogenase (LDH), a gold standard marker for the occurrence of plasma membrane rupture i.e. necrosis. Importantly, lentivirus-based over expression of the anti-apoptotic protein BCL-XL abrogates lysosomal rupture, DNA degradation and LDH release, clearly indicating that Cd induces a programmed form of cell death with a necrotic endpoint. PMID- 22677347 TI - Thoracoscopic versus open pulmonary metastasectomy: a prospective, sequentially controlled study. AB - BACKGROUND: Patients with limited metastatic disease in the lung may benefit from metastasectomy. Thoracotomy is considered the gold standard, and video-assisted thoracoscopic surgery (VATS) is controversial because nonimaged nodules may be missed when bimanual palpation is restricted. Against guideline recommendations, metastasectomy with therapeutic intent is now performed by VATS by 40% of thoracic surgeons surveyed. The evidence base for optimal surgical approach is limited to case series and registries, and no comparative surgical studies were observer blinded. METHODS: Patients considered eligible for pulmonary metastasectomy by VATS prospectively underwent high-definition VATS by one surgical team, followed by immediate thoracotomy with bimanual palpation and resection of all palpable nodules by a second surgical team during the same anesthesia. Both surgical teams were blinded during preoperative evaluation of CT scans and during surgery. Primary end points were number and histology of nodules detected. RESULTS: During a 12-month period, 37 patients were included. Both surgical teams observed exactly 55 nodules suspicious of metastases on CT scans. Of these, 51 nodules were palpable during VATS (92%), and during subsequent thoracotomy 29 additional nodules were resected: Six (21%) were metastases, 19 (66%) were benign lesions, three (10%) were subpleural lymph nodes and one was a primary lung cancer. CONCLUSIONS: Modern VATS technology is increasingly used for pulmonary metastasectomy with therapeutic intent, but several nonimaged, and therefore unexpected, nodules are frequently found during subsequent observer blinded thoracotomy. A substantial proportion of these nodules are malignant, and, despite modern imaging and surgical technology, they would have been missed if VATS was used exclusively for metastasectomy with therapeutic intent. PMID- 22677348 TI - Hypocapnia and hypercapnia are predictors for ICU admission and mortality in hospitalized patients with community-acquired pneumonia. AB - OBJECTIVE: The purpose of our study was to examine in patients hospitalized with community acquired pneumonia (CAP) the association between abnormal Pa CO 2 and ICU admission and 30-day mortality. METHODS: A retrospective cohort study was conducted at two tertiary teaching hospitals. Eligible subjects were admitted with a diagnosis of CAP. Arterial blood gas analyses were obtained with measurement of PaCO2 on admission. Multivariate analyses were performed using 30 day mortality and ICU admission as the dependent measures. RESULTS: Data were abstracted on 453 subjects with a documented arterial blood gas analysis. One hundred eighty-nine patients (41%) had normal PaCO2 (35-45 mm Hg), 194 patients (42%) had aPa CO 2 , 35 mm Hg (hypocapnic), and 70 patients (15%) had a Pa CO 2 . 45 mm Hg (hypercapnic).In the multivariate analysis, after adjusting for severity of illness, hypocapnic patients had greater 30-day mortality (OR= 2.84; 95% CI, 1.28-6.30) and a higher need for ICU admission (OR= 2.88;95% CI, 1.68-4.95) compared with patients with normal PaCO2. In addition, hypercapnic patients had a greater 30-day mortality (OR= 3.38; 95% CI, 1.38-8.30) and a higher need for ICU admission(OR =5.35; 95% CI, 2.80-10.23). When patients with COPD were excluded from the analysis,the differences persisted between groups. CONCLUSION: In hospitalized patients with CAP, both hypocapnia and hypercapnia were associated with an increased need for ICU admission and higher 30-day mortality. These findings persisted after excluding patients with CAP and with COPD. Therefore, PaCO2 should be considered for inclusion in future severity stratification criteria to appropriate identified patients who will require a higher level of care and are at risk for increased mortality. PMID- 22677349 TI - Real-time perspectives of surrogate decision-makers regarding critical illness research: findings of focus group participants. AB - OBJECTIVE: We undertook the current investigation to explore how the pressures of serving as a surrogate decision-maker (SDM) for an acutely ill family member influence attitudes regarding clinical investigation. METHODS: We conducted a prospective study involving SDMs for critically ill patients cared for in the ICUs of two urban hospitals. Measurements included participation in focus groups designed to explore perceptions of ICU care and clinical research. Audiotapes were transcribed and analyzed to identify common patterns and themes using grounded theory. Demographic and clinical data were summarized using standard statistical methods. RESULTS: Seventy-four SDMs (corresponding to 24% of eligible patients) participated. Most SDMs were women and described long-term relationships with the patients represented. SDMs described their role as "overwhelming," their emotions were accentuated by the fatigue of the ICU experience, and they relied on family members, social contacts, and religion as sources of support. Altruism was reported as a common motivation for potential study participation, a sentiment often strengthened by the critical illness episode. Although research was viewed as optional, some SDMs perceived invitation for research participation as tacit acknowledgment of therapeutic failure. SDMs expressed a preference for observational studies (perceived as low risk) over interventional designs (perceived as higher risk). Trust in the ICU team and the research enterprise seemed tightly linked. CONCLUSIONS: Despite significant emotional duress, SDMs expressed interest in investigation and described multiple factors motivating participation. Consent processes that minimize the effects of anxiety may be one strategy to enhance recruitment. PMID- 22677350 TI - Screening of pediatric sleep-disordered breathing: a proposed unbiased discriminative set of questions using clinical severity scales. AB - BACKGROUND: Identification of sleep-disordered breathing (SDB) using questionnaires is critical from a clinical and research perspective. However, which questions to use and how well such questionnaires perform has thus far been fraught with substantial uncertainty. We aimed at delineating the usefulness of a set of questions for identifying pediatric SDB. METHODS: Random prospective sampling of urban 5- to 9-year-old children from the community and enriched for habitual snoring underwent overnight sleep study. Subjective indicators or questions were evaluated to further characterize and discriminate SDB. RESULTS: Of 1,133 subjects, 52.8% were habitual snorers. This sample was analyzed based on a clinical grouping (ie, established apnea-hypopnea index cutoffs). Several statistical steps were performed and indicated that complaints can be ranked according to a severity hierarchy: shake child to breathe, apnea during sleep, struggle breathing when asleep, and breathing concerns while asleep, followed by loudness of snoring and snoring while asleep. With a posteriori cutoff, a predictive score > 2.72 on the severity scale was found (ie, area under the curve, 0.79 +/- 0.03; sensitivity, 59.03%; specificity, 82.85%; positive predictive value, 35.4; negative predictive value, 92.7), making this cutoff applicable for confirmatory purposes. CONCLUSIONS: As a result, the set of six hierarchically arranged questions will aid the screening of children at high risk for SDB but cannot be used as the sole diagnostic approach. PMID- 22677351 TI - Impact of the maze procedure and postoperative atrial fibrillation on progression of functional tricuspid regurgitation in patients undergoing degenerative mitral repair. AB - OBJECTIVES: The aim of this study is to investigate the factors contributing to the progression of functional tricuspid regurgitation (TR) after mitral repair for degenerative mitral regurgitation (MR) in relation to pre and postoperative atrial fibrillation (AF) and performance of the maze procedure. METHODS: We assessed 398 patients with less than moderate TR who did not undergo tricuspid valve repair at the time of isolated mitral valve repair for degenerative MR between January 1999 and January 2010. RESULTS: Clinical follow-up was complete in 385 patients (96.7%) with a median follow-up of 48.3 months (range 0.13 148.5). During this time, there were 21 late deaths (5.5%) and 17 major complications (4.4%), including 11 reoperations for MR recurrence (2.9%). On late follow-up echocardiography performed on 395 patients (median 44.6 months, range 6.0-147.3), 34 (9.6%) experienced moderate or greater MR and 16 (4.5%) experienced moderate or greater TR. The 5-year freedom from moderate or greater MR and moderate or greater TR rates were 88.3 +/- 2.1 and 95.3 +/- 1.5%, respectively. Time-updated Cox regression analysis showed that male gender [hazard ratio (HR) 3.83, 95% confidence interval (CI) 1.28-11.40, P = 0.016], New York Heart Association functional class III or IV (HR 2.64, 95% CI 0.88-8.00, P = 0.085), preoperative AF without maze (HR 10.48, 95% CI 2.49-44.21, P = 0.001), and postoperative AF (HR 14.56, 95% CI 4.46-47.58, P < 0.001) were significant risk factors for postoperative moderate or greater TR. Of the 79 patients with preoperative AF, 68 (86.1%) underwent concomitant maze procedures. Of them, eight (11.8%) experienced late AF (>3 months) recurrence. Freedom from AF at 5 years after the concomitant maze procedure was 87.8 +/- 4.6%. CONCLUSIONS: Preoperative AF without the maze procedure and postoperative AF can contribute to the development of moderate or greater functional TR after mitral repair for degenerative MR. PMID- 22677352 TI - Surgical patch angioplasty of the left main coronary artery. AB - Isolated ostial stenosis of the left main coronary artery (LMCA) is rare, occurring in <1% of the patients undergoing coronary angiography. Surgical patch angioplasty (SPA) offers an alternative to conventional coronary artery bypass grafting (CABG) in such cases and is advantageous in restoring more physiological myocardial perfusion, maintaining ostial patency and preserving conduit material. However, a number of early technical failures and high perioperative mortality have limited the generalized uptake of this procedure, and only recently have advances in myocardial protection and novel surgical approaches to the LMCA resulted in a resurgence of the technique. A systematic literature search identified 45 studies incorporating 478 patients undergoing SPA. A variety of patch materials were used, including the pericardium, saphenous vein and internal mammary and pulmonary arteries. Patients were followed up for a mean of 54.4 months. The 30-day mortality was 1.7% and cardiac specific mortality 3.3% at last follow-up. Encouragingly, 92.4% of reported cases (n = 182) showed complete angiographic patency at last follow-up. Our results indicate that SPA may be a viable alternative to CABG in the surgical management of isolated ostial LMCA stenosis. However, no randomized trials have been performed, and it is clear that careful patient selection is essential in minimizing morbidity and mortality in the short- and long-term. Further research is required to allow a direct comparison of SPA to techniques with a more substantial evidence base such as CABG and percutaneous coronary intervention, and to define the optimal patch graft material, elucidating that any beneficial effects arterial patches may have on long-term patency. PMID- 22677353 TI - Acute type A aortic dissection: long-term results and reoperations. AB - OBJECTIVES: The objective of this study was to report long-term results and incidence of reoperations after surgery for acute type A dissection. METHODS: All 232 consecutive patients who underwent surgery for acute type A aortic dissection from 1972 to April 2011 were included. Patient, procedural and follow-up information was obtained from hospital records. RESULTS: Mean age was 57.9 years (standard deviation 13.4 years), 64% were male. In 157 patients, the native aortic valve was preserved, 75 underwent aortic valve replacement (valved conduit 49, aortic allograft 16, mechanical prosthesis 8 and bioprosthesis 2). Thirty-, 60- and 90-day mortalities were 18.1% (n = 42), 19.8% (n = 46) and 21.6% (n = 50), and decreased over time. Thirty-day mortality in the period 2007-11 was 12.5%. During follow-up of hospital survivors (mean duration 7.2 years, range 0.2 25.7 years), 64 patients died. Risk factors for 30-day mortality were preoperative resuscitation and longer cardiopulmonary bypass time. The use of circulatory arrest and biological glue was associated with a lower 30-day mortality. Actuarial survival was 53.4% (95% confidence interval [CI] 45.8-61.0%) after 10 and 29.3% (95% CI 29.9-48.7%) after 15 years. Late survival was comparable for patients with preserved native valves versus patients with various types of valve replacement. Forty-three patients underwent 47 reoperations; for aortic valve insufficiency in 17 patients (12 native valve, 5 allograft), recurrent aortic dissections or aneurysms in 27 and other cardiac operations in 3 . Actuarial freedom from aortic valve reoperation at 10 years was 85.6% for patients with a preserved native aortic valve, 84.8% after allograft implantation and 100% after prosthetic replacement (Tarone-Ware test P = 0.13). Aortic valve preservation in patients presenting with severe aortic insufficiency was associated with an increased risk of aortic valve reoperation. CONCLUSIONS: Acute type A dissection in the current era is associated with a decreasing acceptable operative mortality risk and has a satisfactory long-term survival for hospital survivors. These factors were both involved were associated with a lower 30-day mortality. A substantial proportion of patients will require reoperations on the aortic valve or the aorta. PMID- 22677354 TI - Lymph nodal staging for non-small-cell lung cancer. PMID- 22677355 TI - Expanding indications of the direct cavopulmonary Fontan. PMID- 22677356 TI - Nutritional and metabolic support in patients with amyotrophic lateral sclerosis. AB - Amyotrophic lateral sclerosis (ALS) is the most common form of progressive motor neuron disease and the most devastating neurodegenerative disorder. ALS is characterized by progressive paralysis and respiratory failure leading to death within 3 to 5 years after its onset. Protein-energy malnutrition is a frequent finding in ALS. The pathogenesis of protein-energy malnutrition in ALS is multifactorial. Muscle atrophy, hypophagia, dysphagia, and hypermetabolism play a role in determining the deterioration of nutritional status. A multidisciplinary approach is crucial to set an appropriate plan for metabolic and nutritional support in ALS. Nutritional management incorporates a continuous assessment and implementation of dietary modifications throughout the duration of the disease. The nutritional and metabolic approaches to ALS should start when the diagnosis of ALS is made and should become an integral part of the continuous care to the patient, including nutritional surveillance, dietary counseling, management of dysphagia, and enteral nutrition when needed. Parenteral nutrition is rarely indicated. Standard polymeric enteral formulas are routinely used, usually providing 25 to 30 kcal/kg and protein 0.8 to 1.2 g /kg per day. The use of fiber enriched formulas may help prevent constipation. However, considering the complex metabolic abnormalities of ALS, standard and/or fiber-enriched formulas might not be sufficient to achieve optimal metabolic and nutritional support. Based on the most recent clinical and experimental evidence, it is tempting to hypothesize that personalized nutritional support including specific nutritional substrates could act on disease progression and improve the quality of life and the response to the few and yet scarcely effective, currently available pharmacologic therapies. PMID- 22677357 TI - Vitamin C status and perception of effort during exercise in obese adults adhering to a calorie-reduced diet. AB - OBJECTIVE: Moderate energy restriction and exercise are recommended for effective weight loss. Obese individuals oxidize less fat and report a higher perceived exertion during exercise, characteristics that may negatively influence exercise behavior. Because vitamin C status has been linked to fatigability, we compared the effects of vitamin C supplementation on self-reported fatigue and on the respiratory exchange ratio and the Ratings of Perceived Exertion scale during moderate exercise in healthy obese adults adhering to a hypocaloric diet. METHODS: Twenty adults (4 men and 16 women) were stratified and randomly assigned to receive 500 mg of vitamin C (VC) or placebo (CON) daily for 4 wk while adhering to a vitamin C-controlled, calorie-restricted diet. Feelings of general fatigue as assessed by the Profile of Mood States questionnaire were recorded on a separate day from the exercise session at weeks 0 and 4. Participants walked on a treadmill at an intensity of 50% predicted maximal oxygen consumption for 60 min at weeks 0 and 4, and heart rate, respiratory exchange ratio, and Ratings of Perceived Exertion were recorded. RESULTS: After 4 wk, the two groups lost similar amounts of weight (~ 4 kg), and the respiratory exchange ratio was not altered by group. Heart rate and the Ratings of Perceived Exertion during exercise were significantly decreased in the VC versus the CON group (-11 versus 3 beats/min, P = 0.022, and -1.3 versus +0.1 U, P = 0.001, respectively), and the general fatigue score was decreased 5.9 U for the VC group versus a 1.9 U increase for the CON group (P = 0.001). CONCLUSION: These data provide preliminary evidence that vitamin C status may influence fatigue, heart rate, and perceptions of exertion during moderate exercise in obese individuals. PMID- 22677358 TI - Dietary patterns and C-peptide concentrations in a Japanese working population. AB - OBJECTIVE: It remains unsettled whether dietary patterns play a role in insulin resistance. We assessed the association of major dietary patterns with C-peptide concentrations in a Japanese working population. METHODS: A cross-sectional study was conducted in 456 municipal employees (270 men and 186 women) 21 to 67 y old who participated in a health survey at the time of their periodic checkup. The dietary patterns were derived by using the principal component analysis of the consumption of 52 food and beverage items, which was assessed by a validated brief dietary history questionnaire. Multiple regression analysis was used to estimate the means of C-peptide concentrations across tertiles of each dietary pattern score with the adjustment of potential confounders, including age, body mass index, physical activity, smoking, alcohol drinking, and energy intake. RESULTS: We identified three dietary patterns: healthy, animal food, and Westernized breakfast patterns. The Westernized breakfast pattern was characterized by high intakes of bread, confectionaries, and milk and yogurt but low intakes of rice and alcohol and was inversely associated with C-peptide concentrations in women but not in men. The multivariable-adjusted means of C peptide concentrations were 1.03 ng/mL (95% confidence interval 0.95-1.12), 0.95 ng/mL (95% confidence interval 0.88-1.03), and 0.89 ng/mL (95% confidence interval 0.82-0.97) for the lowest through the highest tertiles of the Westernized breakfast pattern score (P for trend = 0.015) in women. Other dietary patterns were not appreciably associated with C-peptide concentrations. In a subgroup, similar associations were observed between dietary patterns and the homeostasis model assessment of insulin resistance. CONCLUSION: The Westernized breakfast pattern may be associated with a lower insulin resistance in Japanese women. PMID- 22677359 TI - Lipoxins, resolvins, and protectins in the prevention and treatment of diabetic macular edema and retinopathy. AB - Diabetic macular edema and retinopathy are low-grade inflammatory conditions. Infusions of antitumor necrosis factor-alpha (anti-TNF-alpha) antibody and antivascular endothelial growth factor (anti-VEGF) antibody have been shown to be at least partly effective in the treatment of diabetic macular edema and proliferative diabetic retinopathy. Intravitreal therapy of diabetic macular edema by the anti-TNF-alpha antibody has been found to produce significant side effects and anti-VEGF therapy to be ineffective. Nevertheless, these studies have indicated that the suppression of TNF-alpha and other proinflammatory cytokines and VEGF could be of benefit in diabetic macular edema and retinopathy. The retina is rich in polyunsaturated fatty acids, especially in omega-3, and several studies have shown that polyunsaturated fatty acids prevent diabetic retinopathy. Lipoxins, resolvins, and protectins derived from various polyunsaturated fatty acids possess anti-inflammatory actions and suppress the production of interleukin-6, and TNF-alpha and VEGF have antiangiogenic actions. In view of these evidences, I propose that lipoxins, resolvins, and protectins could be of significant benefit in the prevention and management of diabetic macular edema and retinopathy. PMID- 22677360 TI - The Gly460Trp polymorphism of alpha-adducin gene as a predictor of renal function decline over 4 years of follow-up in an apparently healthy Chinese population. AB - There were conflict data between alpha-adducin Gly460Trp genetic variant and changes of renal function. We conducted a prospective study to investigate the influence of alph-adducin Gly460Trp polymorphism on the quantitative changes of renal function. Of 1500 people screened, 112 non-diabetic normotensive elderly Chinese were recruited and received biochemistry examination at the baseline, at the second and fourth year follow-up. Serum creatinine and calculated renal parameter, using Modification of Diet in Renal Disease (MDRD) Study, were used to evaluate renal function and their progression. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism. Age was 71.9 +/- 3.7 years (range 60-81). Serum creatinine and MDRD glomerular filtration rate (GFR) were significantly worsened at the 2 and 4-year follow-up (all P < 0.001). The magnitude of 4-year decline of MDRD GFR was significantly higher in subjects carrying the a-adducin Gly460Trp G-allele than TT genotype (P = 0.045). The multivariate analyses showed that a-adducin Gly460Trp (P = 0.034), baseline MDRD GFR (P < 0.001), diastolic blood pressure (P = 0.021) and body weight (P = 0.022) could independently predict 4-year change of MDRD GFR. This longitudinal study showed that the aging process was associated with decline of renal function in the healthy elderly. The alpha-adducin Gly460Trp gene polymorphism might modulate these changes in the Chinese. This provides further knowledge essential in the assessment of renal disease and determination of renal function in the older subjects. PMID- 22677362 TI - Cantharidin-induced inflammation in mouse ear model for translational research of novel anti-inflammatories. AB - The murine model of cantharidin-induced ear inflammation was profiled in detail for its alignment with the human model and to explore the mechanism of anti inflammatory activity of the macrolide antibiotics, clarithromycin and azithromycin. Ear swelling in CD1 mice persisted for 7 days, with peak intensity at 16 h after inflammation induction. As in humans, cantharidin (12.5 MUg/ear) generated macrophage-inflammatory protein (MIP)-2, monocyte chemoattractant protein (MCP)-1, keratinocyte-derived chemokine (KC), interleukin (IL)-6, IL 1beta, and myeloperoxidase (MPO) production, as well as neutrophil accumulation in mouse ear tissue. The tested macrolides, clarithromycin and azithromycin, administered orally (2 * 150 mg/kg) 0.5 h before and 5 h after cantharidin challenge, reduced MIP-2, MCP-1, KC, and MPO concentrations and thereby decreased ear swelling. Our results suggest that cantharidin-induced acute inflammation represents an excellent model for translational research of novel anti inflammatories. PMID- 22677361 TI - Pioglitazone, a PPAR-gamma activator, attenuates the severity of cerulein-induced acute pancreatitis by modulating early growth response-1 transcription factor. AB - The purpose of this study was to test the hypothesis that activation of endogenous peroxisome proliferator-activated receptor (PPARgamma) inhibits induction of early growth response factor-1 (Egr-1), which is rapidly induced in the pancreas following cerulein intraperitoneal injection. Acute pancreatitis was induced in mice by hourly intraperitoneal injection of cerulein. Pioglitazone was administered prophylactically and pancreatic inflammation was assessed. AR42J cells were stimulated with caerulein 10-8 M co-incubated in presence of different concentration of pioglitazone. The expression of PPARgamma, Egr-1, and the target genes of Egr-1 were studied by real-time reverse transcriptase polymerase chain reaction (PCR), Western blot, and immunohistochemistry. In vitro, a PPAR-gamma activator (pioglitazone) strikingly diminished Egr-1 mRNA and protein expression corresponding to Egr-1. In vivo, treatment with pioglitazone prior to the intraperitoneal injection of cerulein induction of Egr-1 and its target genes such as, monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1 (MIP-1). The inhibitory effect of pioglitazone on Egr-1 expression induced by cerulein was almost fully restored by GW9662. Activation of PPAR-gamma suppressed the activation of Egr-1 and its inflammatory gene targets and provided potent protection against pancreas injury. These data suggest a new mechanism in which PPAR-gamma activation may decrease tissue inflammation in response to a cerulein insult. PMID- 22677363 TI - Tanshinone II-A inhibits oxidized LDL-induced LOX-1 expression in macrophages by reducing intracellular superoxide radical generation and NF-kappaB activation. AB - Lectin-like oxidized LDL (oxLDL) receptor-1 (LOX-1), a novel scavenger receptor highly expressed in human and experimental atherosclerotic lesions, is responsible for the uptake of oxLDL in vascular cells. We demonstrated previously that Tanshinone II-A (Tan), a pharmacologically active compound extracted from the rhizome of the Chinese herb Salvia miltiorrhiza Bunge, inhibits atherogenesis in hypercholesterolemic rats, rabbits, and apolipoprotein-E deficient (ApoE-/-) mice. However, the precise mechanism by which Tan protects against atherogenesis remains to be elucidated. Therefore, we hypothesized that Tan can suppress the uptake of oxLDL by diminishing the expression of LOX-1 via suppression of NF kappaB signaling pathway, thereby contributing to reduced macrophage foam cell formation. In cultured murine macrophages, oxLDL induced LOX-1 expression at the mRNA and protein levels, was abrogated by addition of Tan or pyrrolidinedithiocarbamic acid ammonium salt (PDTC), a widely used inhibitor of NF-kappaB, suggesting the involvement of NF-kappaB. Tan also reduced LOX-1 expression in atherosclerotic lesions of ApoE-/- mice fed a high cholesterol diet. Mechanistically, Tan suppressed the nuclear translocation of NF-kappaB P65 subunit and phosphorylation of IkappaB-alpha induced by oxLDL. Electrophoretic mobility shift assay (EMSA) demonstrated that Tan inhibited the nuclear protein binding to NF-kappaB consensus sequence. Functionally, we observed that Tan inhibited DiI-oxLDL uptake by macrophages in a fashion similar to that produced by LOX-1 neutralizing antibody. Our current findings reveal a novel mechanism by which Tan protects against atherogenesis and shed new light on the potential therapeutic application of Tan to the treatment and prevention of atherosclerotic cardiovascular diseases. PMID- 22677364 TI - An inflammation-based prognostic index predicts survival advantage after transarterial chemoembolization in hepatocellular carcinoma. AB - Transarterial chemoembolization (TACE) is the preferred treatment for unresectable, intermediate-stage hepatocellular carcinoma (HCC). However, survival after TACE can be highly variable, suggesting the need for more accurate patient selection to improve therapeutic outcome. We have explored the prognostic ability of the blood neutrophil-to-lymphocyte ratio (NLR), a biomarker of systemic inflammation, as a predictor of survival after TACE. Fifty-four patients with a diagnosis of HCC eligible for TACE were selected. Clinicopathologic variables were collected, including demographics, tumor staging, liver functional reserve, and laboratory variables. Dynamic changes in the NLR before and after TACE were studied as predictors of survival using both a univariate and multivariate Cox regression model. Patients in whom the NLR remained stable or normalized after TACE showed a significant improvement in overall survival of 26 months compared with patients showing a persistently abnormal index (P = 0.006). Other predictors of survival on univariate analysis were Cancer of the Liver Italian Program score (P = 0.05), intrahepatic spread (P = 0.01), tumor diameter > 5 cm (P = 0.02), > 1 TACE (P = 0.01), alpha-fetoprotein >= 400 (P = 0.002), and radiologic response to TACE (P < 0.001). Improved NLR after TACE (P = 0.03) and radiologic response after TACE (P = 0.003) remained independent predictors of survival on multivariate analysis. Changes in alpha-fetoprotein after treatment did not predict survival. Patients with a persistently increased NLR have a worse outcome after TACE. NLR is a simple and universally available stratifying biomarker that can help identify patients with a significant survival advantage after TACE. PMID- 22677365 TI - Phytoremediation of heavy metals from fly ash pond by Azolla caroliniana. AB - Abundance of naturally growing Azolla caroliniana (water fern) on the surface of metal enriched fly ash (FA) pond reflects its toxitolerant characteristics. Results indicate the efficiency of A. caroliniana for phytoremediation of FA pond because of its higher bioconcentration factor. The metal concentration ranged from 175 to 538 and 86 to 753mgkg(-1) in roots and fronds, respectively. Bioconcentration factor (BCF) values of all metals in root and frond ranged from 1.7 to18.6 and 1.8 to 11.0, respectively, which were greater than one and indicates the metal accumulation potential of A. caroliniana. Translocation factor (TF) ranged from 0.37 to 1.4 for various heavy metals. The field result proved that A. caroliniana is a potential accumulator for the examined heavy metals and can be used for phytoremediation of FA pond. PMID- 22677366 TI - Occurrence of breast cancer after chest wall irradiation for pediatric cancer, as detected by a multimodal screening program. AB - PURPOSE: To assess the occurrence of breast cancer (BC) after exposure to ionizing radiation for pediatric cancer, by means of a multimodal screening program. PATIENTS AND METHODS: We identified 86 patients who had received chest wall radiation therapy for pediatric cancer. Clinical breast examination (CBE), ultrasound (US), and mammography (MX) were performed yearly. Magnetic resonance imaging (MRI) was added as of October 2007. We calculated the risk of developing BC by radiation therapy dose, patient age, and menarche before or after primary treatment. RESULTS: Eleven women developed a BC from July 2002-February 2010. The sensitivity of the screening methods was 36% for CBE, 73% for MX, 55% for US, and 100% for MRI; the specificity was 91%, 99%, 95%, and 80% for CBE, MX, US, and MRI, respectively. The annual BC detection rate was 2.9%. The median age at BC diagnosis was 33 years. Although age had no influence, menarche before as opposed to after radiation therapy correlated significantly with BC (P=.027): the annual BC detection rate in the former subgroup was 5.3%. CONCLUSIONS: Mammography proved more sensitive and specific in our cohort of young women than CBE or US. Magnetic resonance imaging proved 100% sensitive (but this preliminary finding needs to be confirmed). Our cohort of patients carries a 10-fold BC risk at an age more than 20 years younger than in the general population. PMID- 22677367 TI - A multicenter phase II trial of S-1 with concurrent radiation therapy for locally advanced pancreatic cancer. AB - PURPOSE: The aim of this trial was to evaluate the efficacy and toxicity of S-1 and concurrent radiation therapy for locally advanced pancreatic cancer (PC). METHODS AND MATERIALS: Locally advanced PC patients with histologically or cytologically confirmed adenocarcinoma or adenosquamous carcinoma, who had no previous therapy were enrolled. Radiation therapy was delivered through 3 or more fields at a total dose of 50.4 Gy in 28 fractions over 5.5 weeks. S-1 was administered orally at a dose of 80 mg/m2 twice daily on the day of irradiation during radiation therapy. After a 2- to 8-week break, patients received a maintenance dose of S-1 (80 mg/m2/day for 28 consecutive days, followed by a 14 day rest period) was then administered until the appearance of disease progression or unacceptable toxicity. The primary efficacy endpoint was survival, and the secondary efficacy endpoints were progression-free survival, response rate, and serum carbohydrate antigen 19-9 (CA19-9) response; the safety endpoint was toxicity. RESULTS: Of the 60 evaluable patients, 16 patients achieved a partial response (27%; 95% confidence interval [CI], 16%-40%). The median progression-free survival period, overall survival period, and 1-year survival rate of the evaluable patients were 9.7 months (95% CI, 6.9-11.6 months), 16.2 months (95% CI, 13.5-21.3 months), and 72% (95%CI, 59%-82%), respectively. Of the 42 patients with a pretreatment serum CA19-9 level of >=100 U/ml, 34 (81%) patients showed a decrease of greater than 50%. Leukopenia (6 patients, 10%) and anorexia (4 patients, 7%) were the major grade 3-4 toxicities with chemoradiation therapy. CONCLUSIONS: The effect of S-1 with concurrent radiation therapy in patients with locally advanced PC was found to be very favorable, with only mild toxicity. PMID- 22677368 TI - Robustness against interfraction prostate movement in scanned ion beam radiation therapy. AB - PURPOSE: To assess the robustness of scanned ion beam treatment plans against the interfraction internal target motion and evaluate the limits of validity of target-based isocenter realignment for prostate cancer radiation therapy. METHODS AND MATERIALS: For 12 prostate patients, scanned beam carbon ion treatment plans were prepared using 2 lateral opposed beams and the raster scanning technique with different clinical target volume (CTV) to planning target volume (PTV) margins (2-10 mm). Internal target motion of 2-15 mm in anteroposterior (AP), superoinferior (SI), and left-to-right (LR) directions was simulated by displacing the CTV contours with respect to the computed tomography data. The plans were recalculated with and without target-based isocenter realignment and the CTV coverage was assessed. RESULTS: For CTV shifts within the applied planning margin, the CI-98% is greater than 98.0%, both with and without isocenter realignment. Without realignment, because of the sharp lateral gradients, the CI-98% shows rapid fall as soon as the target shift exceeds the applied planning margin for all displacement directions. With isocenter realignment, the coverage improves notably for shifts in AP and SI directions and the CI-98% is restored to >95.0% for plans optimized with a 2-mm margin, >97% with a 3-mm margin, and >98% with larger margins. For large corrections, predominately in AP direction, cold spots in the CTV may occur. Their magnitude is dependent on the patients' individual anatomies. CONCLUSIONS: Within the physiological limits of internal prostate movement, target-based isocenter realignment results in improved CTV coverage for shifts in AP and SI directions exceeding the applied planning margin. Assuming optimal patient setup reproducibility (eg, immobilization, setup error correction, patient preparation protocols), hence negligible interfraction bone and soft-tissue variations, changes in traversed densities resulting from target-based realignment applied with a reduced planning margin do not induce significant dose deterioration in most of the cases. PMID- 22677369 TI - A dosimetric comparison of tomotherapy and volumetric modulated arc therapy in the treatment of high-risk prostate cancer with pelvic nodal radiation therapy. AB - PURPOSE: To compare the dosimetric results of volumetric modulated arc therapy (VMAT) and helical tomotherapy (HT) in the treatment of high-risk prostate cancer with pelvic nodal radiation therapy. METHODS AND MATERIALS: Plans were generated for 10 consecutive patients treated for high-risk prostate cancer with prophylactic whole pelvic radiation therapy (WPRT) using VMAT and HT. After WPRT, a sequential boost was delivered to the prostate. Plan quality was assessed according to the criteria of the International Commission on Radiation Units and Measurements 83 report: the near-minimal (D98%), near-maximal (D2%), and median (D50%) doses; the homogeneity index (HI); and the Dice similarity coefficient (DSC). Beam-on time, integral dose, and several organs at risk (OAR) dosimetric indexes were also compared. RESULTS: For WPRT, HT was able to provide a higher D98% than VMAT (44.3 +/- 0.3 Gy and 43.9 +/- 0.5 Gy, respectively; P=.032) and a lower D2% than VMAT (47.3 +/- 0.3 Gy and 49.1 +/- 0.7 Gy, respectively; P=.005), leading to a better HI. The DSC was better for WPRT with HT (0.89 +/- 0.009) than with VMAT (0.80 +/- 0.02; P=.002). The dosimetric indexes for the prostate boost did not differ significantly. VMAT provided better rectum wall sparing at higher doses (V70, V75, D2%). Conversely, HT provided better bladder wall sparing (V50, V60, V70), except at lower doses (V20). The beam-on times for WPRT and prostate boost were shorter with VMAT than with HT (3.1 +/- 0.1 vs 7.4 +/- 0.6 min, respectively; P=.002, and 1.5 +/- 0.05 vs 3.7 +/- 0.3 min, respectively; P=.002). The integral dose was slightly lower for VMAT. CONCLUSION: VMAT and HT provided very similar and highly conformal plans that complied well with OAR dose-volume constraints. Although some dosimetric differences were statistically significant, they remained small. HT provided a more homogeneous dose distribution, whereas VMAT enabled a shorter delivery time. PMID- 22677370 TI - Hypofractionated high-dose radiation therapy for prostate cancer: long-term results of a multi-institutional phase II trial. AB - PURPOSE: To report late gastrointestinal (GI) and genitourinary (GU) toxicity, biochemical and clinical outcomes, and overall survival after hypofractionated radiation therapy for prostate cancer (PC). METHODS AND MATERIALS: Three institutions included 113 patients with T1 to T3N0M0 PC in a phase II study. Patients were treated with 56 Gy in 16 fractions over 4 weeks. Late toxicity was scored using Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria extended with additional symptoms. Biochemical outcome was reported according to the Phoenix definition for biochemical failure. RESULTS: The incidence of late GI and GU toxicity was low. The 3-year actuarial risk of developing late GU and GI toxicity of grade>=2 was 13% and 8% respectively. Five-year biochemical non-evidence of disease (bNED) was 94%. Risk group, T stage, and deviation from planned hormone treatment were significant predictive factors for bNED. Deviation from hormone treatment remained significant in multivariate analysis. Five-year clinical non evidence of disease and overall survival was 95% and 91% respectively. No patient died from PC. CONCLUSIONS: Hypofractionated high-dose radiation therapy is a valuable treatment option for patients with PC, with excellent biochemical and clinical outcome and low toxicity. PMID- 22677371 TI - Wound complications in preoperatively irradiated soft-tissue sarcomas of the extremities. AB - PURPOSE: To determine whether the involvement of plastic surgery and the use of vascularized tissue flaps reduces the frequency of major wound complications after radiation therapy for soft-tissue sarcomas (STS) of the extremities. METHODS AND MATERIALS: This retrospective study evaluated patients with STS of the extremities who underwent radiation therapy before surgery. Major complications were defined as secondary operations with anesthesia, seroma/hematoma aspirations, readmission for wound complications, or persistent deep packing. RESULTS: Between 1996 and 2010, 73 patients with extremity STS were preoperatively irradiated. Major wound complications occurred in 32% and secondary operations in 16% of patients. Plastic surgery closed 63% of the wounds, and vascularized tissue flaps were used in 22% of closures. When plastic surgery performed closure the frequency of secondary operations trended lower (11% vs 26%; P=.093), but the frequency of major wound complications was not different (28% vs 38%; P=.43). The use of a vascularized tissue flap seemed to have no effect on the frequency of complications. The occurrence of a major wound complication did not affect disease recurrence or survival. For all patients, 3 year local control was 94%, and overall survival was 72%. CONCLUSIONS: The rates of wound complications and secondary operations in this study were very similar to previously published results. We were not able to demonstrate a significant relationship between the involvement of plastic surgery and the rate of wound complications, although there was a trend toward reduced secondary operations when plastic surgery was involved in the initial operation. Wound complications were manageable and did not compromise outcomes. PMID- 22677373 TI - Mean absorbed dose to the anal-sphincter region and fecal leakage among irradiated prostate cancer survivors. AB - PURPOSE: To supplement previous findings that the absorbed dose of ionizing radiation to the anal sphincter or lower rectum affects the occurrence of fecal leakage among irradiated prostate-cancer survivors. We also wanted to determine whether anatomically defining the anal-sphincter region as the organ at risk could increase the degree of evidence underlying clinical guidelines for restriction doses to eliminate this excess risk. METHODS AND MATERIALS: We identified 985 men irradiated for prostate cancer between 1993 and 2006. In 2008, we assessed long-term gastrointestinal symptoms among these men using a study specific questionnaire. We restrict the analysis to the 414 men who had been treated with external beam radiation therapy only (no brachytherapy) to a total dose of 70 Gy in 2-Gy daily fractions to the prostate or postoperative prostatic region. On reconstructed original radiation therapy dose plans, we delineated the anal-sphincter region as an organ at risk. RESULTS: We found that the prevalence of long-term fecal leakage at least once per month was strongly correlated with the mean dose to the anal-sphincter region. Examining different dose intervals, we found a large increase at 40 Gy; >= 40 Gy compared with <40 Gy gave a prevalence ratio of 3.8 (95% confidence interval 1.6-8.6). CONCLUSIONS: This long term study shows that mean absorbed dose to the anal-sphincter region is associated with the occurrence of long-term fecal leakage among irradiated prostate-cancer survivors; delineating the anal-sphincter region separately from the rectum and applying a restriction of a mean dose <40 Gy will, according to our data, reduce the risk considerably. PMID- 22677372 TI - Variation in telangiectasia predisposing genes is associated with overall radiation toxicity. AB - PURPOSE: In patients receiving radiotherapy for breast cancer where the heart is within the radiation field, cutaneous telangiectasiae could be a marker of potential radiation-induced heart disease. We hypothesized that single nucleotide polymorphisms (SNPs) in genes known to cause heritable telangiectasia-associated disorders could predispose to such late, normal tissue vascular damage. METHODS AND MATERIALS: The relationship between cutaneous telangiectasia as a late normal tissue radiation injury phenotype in 633 breast cancer patients treated with radiotherapy was examined. Patients were clinically assessed for the presence of cutaneous telangiectasia and genotyped at nine SNPs in three candidate genes. Candidate SNPs were within the endoglin (ENG) and activin A receptor, type II like 1 (ACVRL1) genes, mutations in which cause hereditary hemorrhagic telangiectasia and the ataxia-telangiectasia mutated (ATM) gene associated with ataxia-telangiectasia. RESULTS: A total of 121 (19.1%) patients exhibited a degree of cutaneous telangiectasiae on clinical examination. Regression was used to examine the associations between the presence of telangiectasiae in patients who underwent breast-conserving surgery, controlling for the effects of boost and known brassiere size (n=388), and individual geno- or haplotypes. Inheritance of ACVRL1 SNPs marginally contributed to the risk of cutaneous telangiectasiae. Haplotypic analysis revealed a stronger association between inheritance of a ATM haplotype and the presence of cutaneous telangiectasiae, fibrosis and overall toxicity. No significant association was observed between telangiectasiae and the coinheritance of the candidate ENG SNPs. CONCLUSIONS: Genetic variation in the ATM gene influences reaction to radiotherapy through both vascular damage and increased fibrosis. The predisposing variation in the ATM gene will need to be better defined to optimize it as a predictive marker for assessing radiotherapy late effects. PMID- 22677374 TI - Sudden unexpected death in epilepsy: trying to reset the clock on diabetes. PMID- 22677375 TI - How do parents find out about the ketogenic diet? AB - It has been previously reported that child neurologists often view the ketogenic diet (KD) as a treatment of last resort. An anonymous survey was provided to parents of 107 consecutive children starting the KD at our institution. The average time from epilepsy to KD onset was 2.8years, but the average wait time for KD onset was only 1.7months after referral. The most common reason for starting the KD was seizure reduction, followed by less intense seizures, medication reduction, and cognitive improvement. The majority (72%) obtained information about the KD from their neurologist; however, more than half also had viewed related websites. The mean neurologist supportiveness score was 7.9/10; 53% reporting their neurologist as maximally supportive (score of 10). A score of 10 was more likely seen in those who also scored their pediatrician with 10 (69% vs. 15%, p<0.001) and who were self-referred from our institution (56% vs. 27%, p=0.001). PMID- 22677376 TI - Nucleosome dynamics between tension-induced states. AB - We studied the dynamical behavior of a mononucleosome under tension using a theoretical model that takes into account the nucleosomal geometry, DNA elasticity, nonspecific DNA-protein binding, and effective repulsion between the two DNA turns. Using a dynamical Monte-Carlo simulation algorithm, we demonstrate that this model shows a behavior that for an appropriate set of parameters is in quantitative agreement with data from micromanipulation experiments on individual nucleosomes. All of the parameters of the model follow from the data obtained from two types of pulling experiments, namely, constant force and constant loading rate ensembles. PMID- 22677377 TI - Mapping three-dimensional stress and strain fields within a soft hydrogel using a fluorescence microscope. AB - Three-dimensional cell culture is becoming mainstream as it is recognized that many animal cell types require the biophysical and biochemical cues within the extracellular matrices to perform truly physiologically realistic functions. However, tools for characterizing cellular mechanical environment are largely limited to cell culture plated on a two-dimensional substrate. We present a three dimensional traction microscopy that is capable of mapping three-dimensional stress and strain within a soft and transparent extracellular matrix using a fluorescence microscope and a simple forward data analysis algorithm. We validated this technique by mapping the strain and stress field within the bulk of a thin polyacrylamide gel layer indented by a millimeter-size glass ball, together with a finite-element analysis. The experimentally measured stress and strain fields are in excellent agreements with results of the finite-element simulation. The unique contributions of the presented three-dimensional traction microscopy technique are: 1), the use of a fluorescence microscope in contrast with the confocal microscope that is required for the current three-dimensional traction microscopes in the literature; 2), the determination of the pressure field of an incompressible gel from strains; and 3), the simple forward-data analysis algorithm. Future application of this technique for mapping animal cell traction in three-dimensional nonlinear biological gels is discussed. PMID- 22677378 TI - Regulation of the DNA damage response by p53 cofactors. AB - The selective expression of p53-targeted genes is central to the p53-mediated DNA damage response. It is affected by multiple factors including posttranslational modifications and cofactors of p53. Here, we proposed an integrated model of the p53 network to characterize how the cellular response is regulated by key cofactors of p53, Hzf and ASPP. We found that the sequential induction of Hzf and ASPP is crucial to a reliable cell-fate decision between survival and death. After DNA damage, activated p53 first induces Hzf, which promotes the expression of p21 to arrest the cell cycle and facilitate DNA repair. The cell recovers to normal proliferation after the damage is repaired. If the damage is beyond repair, Hzf is effectively degraded, and activated E2F1 induces ASPP, which promotes the expression of Bax to trigger apoptosis. Furthermore, interrupting the induction of Hzf or ASPP remarkably impairs the cellular function. We also proposed two schemes for the production of the unknown E3 ubiquitin ligase for Hzf degradation: it is induced by either E2F1 or p53. In both schemes, the sufficient degradation of Hzf is required for apoptosis induction. These results are in good agreement with experimental observations or are experimentally testable. PMID- 22677379 TI - Identification of different proaggregatory abilities of activated platelet subpopulations. AB - Blood platelets are anucleate cell fragments that play a critically important role in hemostasis and thrombosis. Platelets are activated with various agonists that allow them to aggregate, thus forming either hemostatic plugs or pathologic thrombi. Recent studies have revealed that at least two activated platelet subpopulations are formed upon potent stimulation of platelets with collagen and/or thrombin. One of these subpopulations consists of so-called coated platelets that express high levels of phosphatidylserine and retain alpha-granule proteins, including fibrinogen, on their surface. They also have reduced levels of the main aggregation receptor-activated glycoprotein IIb-IIIa, which might indicate a defect in their proaggregatory ability. In this study, the proaggregatory abilities of coated and noncoated platelets were assessed by means of light transmission aggregometry of suspensions with varying ratios of platelets from one subpopulation to those of a different subpopulation. A mathematical model of platelet aggregation in heterogeneous mixtures was developed to assist in the analysis of experimental data. Flow cytometry was employed to monitor platelet recruitment into aggregates and the ability of platelets to bind external fibrinogen. Finally, confocal microscopy was used to image coated platelets involved into aggregates formed by mechanical shaking. The obtained data revealed to our knowledge a novel mechanism regulating aggregate formation of platelet subpopulations: coated platelets cannot aggregate with each other but can be recruited into aggregates by noncoated platelets. PMID- 22677380 TI - The influenza fusion peptide adopts a flexible flat V conformation in membranes. AB - Knowledge about the influenza fusion peptide (FP) membrane insertion mode is crucial for understanding its fusogenic mechanism. NMR and electron paramagnetic resonance experiments showed that in micelles, the FP inserted as a fixed-angle inverted V. In membranes, however, it was shown to insert as a straight alpha helix (by molecular-dynamics simulations) and to adopt multiple kinked conformations (by solid-state NMR). In this work we performed explicit-solvent molecular-dynamics simulations of the influenza FP, and its F9A and W14A mutants, in POPC membranes. The Halpha1 chemical shifts predicted from the molecular dynamics structures are in excellent agreement with the experimental values obtained for the three peptides. The peptide orientation and conformations observed from the simulations lead to a flexible flat-V model in which the peptide lies almost flat on the membrane surface and alternates between kinked and straight-helix conformations. PMID- 22677381 TI - Hydrophobic mismatch and lipid sorting near OmpA in mixed bilayers: atomistic and coarse-grained simulations. AB - To understand the effects of lipid composition on membrane protein function in a mixture as complex as a biomembrane, one must know whether the lipid composition local to the protein differs from the mean lipid composition. In this study, we simulated the transmembrane domain of a beta-barrel protein, OmpA, in mixtures of lipids of different tail lengths under conditions of negative hydrophobic mismatch, i.e., local bilayer thinning. We modeled the influence of OmpA on the local lipid composition both at a coarse-grained (CG) resolution using conventional molecular dynamics, and at an atomistic resolution within the semi grand canonical ensemble using mutation moves to rapidly approach an equilibrium lateral distribution of lipids. Moderate enrichment of the shorter tail component (either DDPC in DDPC/DMPC mixtures or DMPC in DMPC/DSPC mixtures) extending 2-3 nm away from the protein surface was observed with both the atomistic and CG models. The similarity in trends suggests that the more computationally economical CG models capture the essential features of lipid sorting induced by hydrophobic mismatch. PMID- 22677382 TI - A Bayesian inference scheme to extract diffusivity and potential fields from confined single-molecule trajectories. AB - Currently used techniques for the analysis of single-molecule trajectories only exploit a small part of the available information stored in the data. Here, we apply a Bayesian inference scheme to trajectories of confined receptors that are targeted by pore-forming toxins to extract the two-dimensional confining potential that restricts the motion of the receptor. The receptor motion is modeled by the overdamped Langevin equation of motion. The method uses most of the information stored in the trajectory and converges quickly onto inferred values, while providing the uncertainty on the determined values. The inference is performed on the polynomial development of the potential and on the diffusivities that have been discretized on a mesh. Numerical simulations are used to test the scheme and quantify the convergence toward the input values for forces, potential, and diffusivity. Furthermore, we show that the technique outperforms the classical mean-square-displacement technique when forces act on confined molecules because the typical mean-square-displacement analysis does not account for them. We also show that the inferred potential better represents input potentials than the potential extracted from the position distribution based on Boltzmann statistics that assumes statistical equilibrium. PMID- 22677385 TI - Generalized facilitated diffusion model for DNA-binding proteins with search and recognition states. AB - Transcription factors (TFs) such as the lac repressor find their target sequence on DNA at remarkably high rates. In the established Berg-von Hippel model for this search process, the TF alternates between three-dimensional diffusion in the bulk solution and one-dimensional sliding along the DNA chain. To overcome the so called speed-stability paradox, in similar models the TF was considered as being present in two conformations (search state and recognition state) between which it switches stochastically. Combining both the facilitated diffusion model and alternating states, we obtain a generalized model. We explicitly treat bulk excursions for rodlike chains arranged in parallel and consider a simplified model for coiled DNA. Compared to previously considered facilitated diffusion models, corresponding to limiting cases of our generalized model, we surprisingly find a reduced target search rate. Moreover, at optimal conditions there is no longer an equipartition between the time spent by the protein on and off the DNA chain. PMID- 22677383 TI - Observing the confinement potential of bacterial pore-forming toxin receptors inside rafts with nonblinking Eu(3+)-doped oxide nanoparticles. AB - We track single toxin receptors on the apical cell membrane of MDCK cells with Eu doped oxide nanoparticles coupled to two toxins of the pore-forming toxin family: alpha-toxin of Clostridium septicum and epsilon-toxin of Clostridium perfringens. These nonblinking and photostable labels do not perturb the motion of the toxin receptors and yield long uninterrupted trajectories with mean localization precision of 30 nm for acquisition times of 51.3 ms. We were thus able to study the toxin-cell interaction at the single-molecule level. Toxins bind to receptors that are confined within zones of mean area 0.40 +/- 0.05 MUm(2). Assuming that the receptors move according to the Langevin equation of motion and using Bayesian inference, we determined mean diffusion coefficients of 0.16 +/- 0.01 MUm(2)/s for both toxin receptors. Moreover, application of this approach revealed a force field within the domain generated by a springlike confining potential. Both toxin receptors were found to experience forces characterized by a mean spring constant of 0.30 +/- 0.03 pN/MUm at 37 degrees C. Furthermore, both toxin receptors showed similar distributions of diffusion coefficient, domain area, and spring constant. Control experiments before and after incubation with cholesterol oxidase and sphingomyelinase show that these two enzymes disrupt the confinement domains and lead to quasi-free motion of the toxin receptors. Our control data showing cholesterol and sphingomyelin dependence as well as independence of actin depolymerization and microtubule disruption lead us to attribute the confinement of both receptors to lipid rafts. These toxins require oligomerization to develop their toxic activity. The confined nature of the toxin receptors leads to a local enhancement of the toxin monomer concentration and may thus explain the virulence of this toxin family. PMID- 22677384 TI - Computational model of cytokinetic abscission driven by ESCRT-III polymerization and remodeling. AB - The endosomal sorting complex required for transport (ESCRT)-III complex, capable of polymerization and remodeling, participates in abscission of the intercellular membrane bridge connecting two daughter cells at the end of cytokinesis. Here, we integrate quantitative imaging of ESCRT-III during cytokinetic abscission with biophysical properties of ESCRT-III complexes to formulate and test a computational model for ESCRT-mediated cytokinetic abscission. We propose that cytokinetic abscission is driven by an ESCRT-III fission complex, which arises from ESCRT-III polymerization at the edge of the cytokinetic midbody structure, located at the center of the intercellular bridge. Formation of the fission complex is completed by remodeling and breakage of the ESCRT-III polymer assisted by VPS4. Subsequent spontaneous constriction of the fission complex generates bending deformation of the intercellular bridge membrane. The related membrane elastic force propels the fission complex along the intercellular bridge away from the midbody until it reaches an equilibrium position, determining the scission site. Membrane attachment to the dome-like end-cap of the fission complex drives membrane fission, completing the abscission process. We substantiate the model by theoretical analysis of the membrane elastic energy and by experimental verification of the major model assumptions. PMID- 22677386 TI - Sequence-specific recognition of cancer drug-DNA adducts by HMGB1a repair protein. AB - The efficacy of cancer drugs such as cisplatin (Cp) and oxaliplatin (Ox), which covalently bind to DNA to form drug-DNA adducts, is linked to their recognition by repair proteins such as HMGB1a. Previous experimental studies showed that HMGB1a's binding affinity for Cp- and Ox-DNA varies with the drug used and the local DNA sequence context of the adduct. We link this differential binding affinity to the free energy of deforming (bending and minor groove opening) the drug-DNA molecule during HMGB1a binding. Specifically, the minimal binding affinity of HMGB1a for Ox-DNA in the TGGA context is explained by its larger deformation free energy compared with Cp-DNA or Ox-DNA in other sequence contexts. Methyl groups on neighboring thymine bases in Ox-TGGA crowd the minor groove and sterically hinder the motion of the diaminocyclohexane ring of Ox, leading to this reduced deformability and resultant decrease in HMGB1a's binding affinity. PMID- 22677387 TI - Degradation of fungal prion HET-s(218-289) induces formation of a generic amyloid fold. AB - The prion-forming domain of the fungal prion protein HET-s, HET-s(218-289), is known from solid-state NMR studies to have a beta-solenoidal structure; the beta solenoid has the cross-beta structure characteristic of all amyloids, but is inherently more complex than the generic stacked beta-sheets found in studies of small synthetic peptides. At low pH HET-s(218-289) has also been reported to form an alternative structure, which has not been characterized. We have confirmed by x-ray fiber diffraction that HET-s(218-289) adopts a beta-solenoidal structure at neutral pH, and shown that at low pH, it forms either a beta-solenoid or a stacked beta-sheet structure, depending on the integrity of the protein and the conditions of fibrillization. The low pH stacked-sheet structure is usually formed only by proteolyzed HET-s(218-289), but intact HET-s(218-289) can form stacked sheets when seeded with proteolyzed stacked-sheet HET-s(218-289). The polymorphism of HET-s parallels the structural differences between the infectious brain-derived and the much less infectious recombinant mammalian prion protein PrP. Taken together, these observations suggest that the functional or pathological forms of amyloid proteins are more complex than the simple generic stacked-sheet amyloids commonly formed by short peptides. PMID- 22677388 TI - The power of hard-sphere models: explaining side-chain dihedral angle distributions of Thr and Val. AB - The energy functions used to predict protein structures typically include both molecular-mechanics and knowledge-based terms. In contrast, our approach is to develop robust physics- and geometry-based methods. Here, we investigate to what extent simple hard-sphere models can be used to predict side-chain conformations. The distributions of the side-chain dihedral angle chi(1) of Val and Thr in proteins of known structure show distinctive features: Val side chains predominantly adopt chi(1) = 180 degrees , whereas Thr side chains typically adopt chi(1) = 60 degrees and 300 degrees (i.e., chi(1) = +/-60 degrees or g- and g(+) configurations). Several hypotheses have been proposed to explain these differences, including interresidue steric clashes and hydrogen-bonding interactions. In contrast, we show that the observed side-chain dihedral angle distributions for both Val and Thr can be explained using only local steric interactions in a dipeptide mimetic. Our results emphasize the power of simple physical approaches and their importance for future advances in protein engineering and design. PMID- 22677389 TI - A physics-based approach of coarse-graining the cytoplasm of Escherichia coli (CGCYTO). AB - We have investigated protein stability in an environment of Escherichia coli cytoplasm using coarse-grained computer simulations. To coarse-grain a small slide of E. coli's cytoplasm consisting of over 16 million atoms, we have developed a self-assembled clustering algorithm (CGCYTO). CGCYTO uses the shape parameter and asphericity as well as a parameter lambda (ranging from 0 to 1) that measures the covolume of a test protein and a macromolecule against the covolume of a test protein and a sphere of equal volume as that of a macromolecule for the criteria of coarse-graining a cytoplasmic model. A cutoff lambda(c) = 0.8 was chosen based on the size of a test protein and computational resources and it determined the resolution of a coarse-grained cytoplasm. We compared the results from a polydisperse cytoplasmic model (PD model) produced by CGCYTO with two other coarse-grained hard-sphere cytoplasmic models: 1), F70 model, macromolecules in the cytoplasm were modeled by homogeneous hard spheres with a radius of 55 A, the size of Ficoll70 and 2), HS model, each macromolecule in the cytoplasm was modeled by a hard sphere of equal volume. It was found that the folding temperature T(f) of a test protein (apoazurin) in a PD model is ~5 degrees greater than that in a F70 model. In addition, the deviation of T(f) in a PD model is twice as much as that in a HS model when an apoazurin is randomly placed at different voids formed by particle fluctuations in PD models. PMID- 22677390 TI - Non-bias-limited tracking of spherical particles, enabling nanometer resolution at low magnification. AB - We present a three-dimensional tracking routine for nondiffraction-limited particles, which significantly reduces pixel bias. Our technique allows for increased resolution compared to that of previous methods, especially at low magnification or at high signal/noise ratio. This enables tracking with nanometer accuracy in a wide field of view and tracking of many particles. To reduce bias induced by pixelation, the tracking algorithm uses interpolation of the image on a circular grid to determine the x-, y-, and z-positions. We evaluate the proposed algorithm by tracking simulated images and compare it to well-known center-of-mass and cross-correlation methods. The final resolution of the described method improves up to an order of magnitude in three dimensions compared to conventional tracking methods. We show that errors in x,y-tracking can seriously affect z-tracking if interpolation is not used. We validate our results with experimental data obtained for conditions matching those used in the simulations. Finally, we show that the increased performance of the proposed algorithm uniquely enables it to extract accurate data for the persistence length and end-to-end distance of 107 DNA tethers in a single experiment. PMID- 22677391 TI - Structure of immune stimulating complex matrices and immune stimulating complexes in suspension determined by small-angle x-ray scattering. AB - Immune stimulating complex (ISCOM) particles consisting of a mixture of Quil-A, cholesterol, and phospholipids were structurally characterized by small-angle x ray scattering (SAXS). The ISCOM particles are perforated vesicles of very well defined structures. We developed and implemented a novel (to our knowledge) modeling method based on Monte Carlo simulation integrations to describe the SAXS data. This approach is similar to the traditional modeling of SAXS data, in which a structure is assumed, the scattering intensity is calculated, and structural parameters are optimized by weighted least-squares methods when the model scattering intensity is fitted to the experimental data. SAXS data from plain ISCOM matrix particles in aqueous suspension, as well as those from complete ISCOMs (i.e., with an antigen (tetanus toxoid) incorporated) can be modeled as a polydisperse distribution of perforated bilayer vesicles with icosahedral, football, or tennis ball structures. The dominating structure is the tennis ball structure, with an outer diameter of 40 nm and with 20 holes 5-6 nm in diameter. The lipid bilayer membrane is 4.6 nm thick, with a low-electron-density, 2.0-nm thick hydrocarbon core. Surprisingly, in the ISCOMs, the tetanus toxoid is located just below the membrane inside the particles. PMID- 22677392 TI - Long lifetime of hydrogen-bonded DNA basepairs by force spectroscopy. AB - Electron-tunneling data suggest that a noncovalently-bonded complex of three molecules, two recognition molecules that present hydrogen-bond donor and acceptor sites via a carboxamide group, and a DNA base, remains bound for seconds. This is surprising, given that imino-proton exchange rates show that basepairs in a DNA double helix open on millisecond timescales. The long lifetime of the three-molecule complex was confirmed using force spectroscopy, but measurements on DNA basepairs are required to establish a comparison with the proton-exchange data. Here, we report on a dynamic force spectroscopy study of complexes between the bases adenine and thymine (A-T, two-hydrogen bonds) and 2 aminoadenine and thymine (2AA-T, three-hydrogen bonds). Bases were tethered to an AFM probe and mica substrate via long, covalently linked polymer tethers. Data for bond-survival probability versus force and the rupture-force distributions were well fitted by the Bell model. The resulting lifetime of the complexes at zero pulling force was ~2 s for two-hydrogen bonds (A-T) and ~4 s for three hydrogen bonds (2AA-T). Thus, DNA basepairs in an AFM pulling experiment remain bonded for long times, even without the stabilizing influence of base-stacking in a double helix. This result suggests that the pathways for opening, and perhaps the open states themselves, are very different in the AFM and proton-exchange measurements. PMID- 22677393 TI - Statistical deconvolution for superresolution fluorescence microscopy. AB - Superresolution microscopy techniques based on the sequential activation of fluorophores can achieve image resolution of ~10 nm but require a sparse distribution of simultaneously activated fluorophores in the field of view. Image analysis procedures for this approach typically discard data from crowded molecules with overlapping images, wasting valuable image information that is only partly degraded by overlap. A data analysis method that exploits all available fluorescence data, regardless of overlap, could increase the number of molecules processed per frame and thereby accelerate superresolution imaging speed, enabling the study of fast, dynamic biological processes. Here, we present a computational method, referred to as deconvolution-STORM (deconSTORM), which uses iterative image deconvolution in place of single- or multiemitter localization to estimate the sample. DeconSTORM approximates the maximum likelihood sample estimate under a realistic statistical model of fluorescence microscopy movies comprising numerous frames. The model incorporates Poisson distributed photon-detection noise, the sparse spatial distribution of activated fluorophores, and temporal correlations between consecutive movie frames arising from intermittent fluorophore activation. We first quantitatively validated this approach with simulated fluorescence data and showed that deconSTORM accurately estimates superresolution images even at high densities of activated fluorophores where analysis by single- or multiemitter localization methods fails. We then applied the method to experimental data of cellular structures and demonstrated that deconSTORM enables an approximately fivefold or greater increase in imaging speed by allowing a higher density of activated fluorophores/frame. PMID- 22677395 TI - DNA base-calling from a nanopore using a Viterbi algorithm. AB - Nanopore-based DNA sequencing is the most promising third-generation sequencing method. It has superior read length, speed, and sample requirements compared with state-of-the-art second-generation methods. However, base-calling still presents substantial difficulty because the resolution of the technique is limited compared with the measured signal/noise ratio. Here we demonstrate a method to decode 3-bp-resolution nanopore electrical measurements into a DNA sequence using a Hidden Markov model. This method shows tremendous potential for accuracy (~98%), even with a poor signal/noise ratio. PMID- 22677394 TI - Correlating calcium binding, Forster resonance energy transfer, and conformational change in the biosensor TN-XXL. AB - Genetically encoded calcium indicators have become instrumental in imaging signaling in complex tissues and neuronal circuits in vivo. Despite their importance, structure-function relationships of these sensors often remain largely uncharacterized due to their artificial and multimodular composition. Here, we describe a combination of protein engineering and kinetic, spectroscopic, and biophysical analysis of the Forster resonance energy transfer (FRET)-based calcium biosensor TN-XXL. Using fluorescence spectroscopy of engineered tyrosines, we show that two of the four calcium binding EF-hands dominate the FRET output of TN-XXL and that local conformational changes of these hands match the kinetics of FRET change. Using small-angle x-ray scattering and NMR spectroscopy, we show that TN-XXL changes from a flexible elongated to a rigid globular shape upon binding calcium, thus resulting in FRET signal output. Furthermore, we compare calcium titrations using fluorescence lifetime spectroscopy with the ratiometric approach and investigate potential non-FRET effects that may affect the fluorophores. Thus, our data characterize the biophysics of TN-XXL in detail and may form a basis for further rational engineering of FRET-based biosensors. PMID- 22677396 TI - A prototypic mathematical model of the human hair cycle. AB - The human hair cycle is a complex, dynamic organ-transformation process during which the hair follicle repetitively progresses from a growth phase (anagen) to a rapid apoptosis-driven involution (catagen) and finally a relative quiescent phase (telogen) before returning to anagen. At present no theory satisfactorily explains the origin of the hair cycle rhythm. Based on experimental evidence we propose a prototypic model that focuses on the dynamics of hair matrix keratinocytes. We argue that a plausible feedback-control structure between two key compartments (matrix keratinocytes and dermal papilla) leads to dynamic instabilities in the population dynamics resulting in rhythmic hair growth. The underlying oscillation consists of an autonomous switching between two quasi steady states. Additional features of the model, namely bistability and excitability, lead to new hypotheses about the impact of interventions on hair growth. We show how in silico testing may facilitate testing of candidate hair growth modulatory agents in human HF organ culture or in clinical trials. PMID- 22677397 TI - Development of the Pseudomonas aeruginosa mushroom morphology and cavity formation by iron-starvation: a mathematical modeling study. AB - We present a mathematical model of mushroom-like architecture and cavity formation in Pseudomonas aeruginosa biofilms. We demonstrate that a proposed disparity in internal friction between the stalk and cap extracellular polymeric substances (EPS) leads to spatial variation in volumetric expansion sufficient to produce the mushroom morphology. The capability of diffusible signals to induce the formation of a fluid-filled cavity within the cap is then investigated. We assume that conversion of bacteria to the planktonic state within the cap occurs in response to the accumulation or depletion of some signal molecule. We (a) show that neither simple nutrient starvation nor signal production by one or more subpopulations of bacteria is sufficient to trigger localized cavity formation. We then (b) demonstrate various hypothetical scenarios that could result in localized cavity formation. Finally, we (c) model iron availability as a detachment signal and show simulation results demonstrating cavity formation by iron starvation. We conclude that iron availability is a plausible mechanism by which fluid-filled cavities form in the cap region of mushroom-like structures. PMID- 22677398 TI - Bistability of endosymbiont evolution of genome size and host sex control. AB - Eukaryotic organisms often harbor several genetic factors in their cytoplasm. These cytoplasmic genetic elements (CGEs) include both eukaryotic organelles (mitochondria, chloroplasts) and bacterial endosymbionts, which have evolved from free-living bacteria. A common feature of CGEs is their cytoplasmic inheritance from mother to offspring. A striking difference is that some CGEs have evolved a short genome size (e.g., animal mitochondria), while others cause a sex ratio distortion (SRD) in their hosts (e.g., Wolbachia). In this study, we sought to resolve the evolution of these endosymbiont properties using a population genetics approach. Our model divides the endosymbiont genome into a functional part and a part that can cause SRD, and our results indicate that the cytoplasmic inheritance system at the initiation of symbiosis plays a key role in determining the evolutionary trajectory of CGEs. We show that in endosymbiotic evolution, two states can be bistable, depending on the parameters. The evolution of the cytoplasmic inheritance system from biparental to uniparental can result in hysteresis in the evolution of cytoplasmic symbionts. PMID- 22677399 TI - The robustness of cyclic dominance under random fluctuations. AB - We investigate the influence of random perturbations on a recently introduced three-species model that reproduces the empirically observed pattern of cyclic dominance in Fraser River sockeye salmon. Since the sockeye populations are subject to various types of fluctuations affecting their growth and survival, we investigate the robustness of the model under several types of noise. In particular, we evaluate the variation of population sizes around their values in the deterministic model, the frequency of phase shifts in the 4-year oscillation, the extent of synchronization between different sockeye populations, and the response to strong one-time perturbations. Our main conclusion is that cyclic dominance is very stable even under strong noise in this model. PMID- 22677400 TI - Model-based selection of the robust JAK-STAT activation mechanism. AB - JAK-STAT pathway family is a principal signaling mechanism in eukaryotic cells. Evolutionary conserved roles of this mechanism include control over fundamental processes such as cell growth or apoptosis. Deregulation of the JAK-STAT signaling is frequently associated with cancerogenesis. JAK-STAT pathways become hyper-activated in many human tumors. Therefore, components of these pathways are an attractive target for drugs, which design requires as adequate models as possible. Although, in principle, JAK-STAT signaling is relatively simple, the ambiguities in a receptor activation prevent a clear explanation of the underlying molecular mechanism. Here, we compare four variants of a computational model of the JAK1/2-STAT1 signaling pathway. These variants capture known, basic discrepancies in the mechanism of activation of a cytokine receptor, in the context of all key components of the pathway. We carry out a comparative analysis using mass action kinetics. The investigated differences are so marginal that all models satisfy a goodness of fit criteria to the extent that the state of the art Bayesian model selection (BMS) method fails to significantly promote one model. Therefore, we comparatively investigate changes in a robustness of the JAK1/2 STAT1 pathway variants using the global sensitivity analysis method (GSA), complemented with the identifiability analysis (IA). Both BMS and GSA are used to analyze the models for the varying parameter values. We found out that, both BMS and GSA, narrowed down to the receptor activation component, slightly promote the least complex model. Further, insightful, comprehensive GSA, motivated by the concept of robustness, allowed us to show that the precise order of reactions of a ligand binding and a receptor dimerization is not as important as the on membrane pre-assembly of the dimers in the absence of ligand. The main value of this work is an evaluation of the usefulness of different model selection methods in a frequently encountered, but not much discussed case of a model of a considerable size, which has several variants differing at peripheries. In such situation, all considered variants can reach nearly perfect agreement with respect to their numerical simulations results and, most often, the sufficient experimental data to test against is not available. We argue that in such an adverse setting, the GSA and IA, although not directly corresponding to the model selection problem, can be more informative than the representative, generalizability-based approaches to this task. An additional insight into how the responsibility for the network dynamics spreads among model parameters, enables more conscious, expert-mediated choice of the preferred model. PMID- 22677401 TI - The use of non-standard CT conversion ramps for Monte Carlo verification of 6 MV prostate IMRT plans. AB - Monte Carlo (MC) dose calculation algorithms have been widely used to verify the accuracy of intensity-modulated radiotherapy (IMRT) dose distributions computed by conventional algorithms due to the ability to precisely account for the effects of tissue inhomogeneities and multileaf collimator characteristics. Both algorithms present, however, a particular difference in terms of dose calculation and report. Whereas dose from conventional methods is traditionally computed and reported as the water-equivalent dose (Dw), MC dose algorithms calculate and report dose to medium (Dm). In order to compare consistently both methods, the conversion of MC Dm into Dw is therefore necessary. This study aims to assess the effect of applying the conversion of MC-based Dm distributions to Dw for prostate IMRT plans generated for 6 MV photon beams. MC phantoms were created from the patient CT images using three different ramps to convert CT numbers into material and mass density: a conventional four material ramp (CTCREATE) and two simplified CT conversion ramps: (1) air and water with variable densities and (2) air and water with unit density. MC simulations were performed using the BEAMnrc code for the treatment head simulation and the DOSXYZnrc code for the patient dose calculation. The conversion of Dm to Dw by scaling with the stopping power ratios of water to medium was also performed in a post-MC calculation process. The comparison of MC dose distributions calculated in conventional and simplified (water with variable densities) phantoms showed that the effect of material composition on dose-volume histograms (DVH) was less than 1% for soft tissue and about 2.5% near and inside bone structures. The effect of material density on DVH was less than 1% for all tissues through the comparison of MC distributions performed in the two simplified phantoms considering water. Additionally, MC dose distributions were compared with the predictions from an Eclipse treatment planning system (TPS), which employed a pencil beam convolution (PBC) algorithm with Modified Batho Power Law heterogeneity correction. Eclipse PBC and MC calculations (conventional and simplified phantoms) agreed well (<1%) for soft tissues. For femoral heads, differences up to 3% were observed between the DVH for Eclipse PBC and MC calculated in conventional phantoms. The use of the CT conversion ramp of water with variable densities for MC simulations showed no dose discrepancies (0.5%) with the PBC algorithm. Moreover, converting Dm to Dw using mass stopping power ratios resulted in a significant shift (up to 6%) in the DVH for the femoral heads compared to the Eclipse PBC one. Our results show that, for prostate IMRT plans delivered with 6 MV photon beams, no conversion of MC dose from medium to water using stopping power ratio is needed. In contrast, MC dose calculations using water with variable density may be a simple way to solve the problem found using the dose conversion method based on the stopping power ratio. PMID- 22677402 TI - The degree of premature hair graying as an independent risk marker for coronary artery disease: a predictor of biological age rather than chronological age. AB - OBJECTIVE: Age is the most important and uncorrectable coronary risk factor at the moment. The concept of measuring aging biologically rather than only chronologically may be of importance in clinical practice. Hair graying is the most apparent sign of biological aging in humans, yet its mechanism is largely unknown. Today, it is known that cardiovascular risk factors (CVRFs), especially in combination, cause premature atherosclerosis. In our opinion, premature hair graying or whitening may represent early atherosclerotic changes as a surrogate of host response to the CVRFs. In this study, we planned to investigate the relationship of hair graying with CVRFs and coronary atherosclerotic burden in order to determine whether it is an independent marker for coronary artery disease (CAD). METHODS: The current study has a cross-sectional observational design. Two hundred and thirteen men who underwent coronary angiography with a suspicion of CAD were enrolled in the study. The patients were evaluated in terms of age, demographical properties and the CVRFs. Hair whitening score (HWS) was defined according to extent of gray/white hairs (1: pure black; 2: black>white; 3: black=white; 4: white>black; 5: pure white). Coronary atherosclerotic burden was assessed by the Gensini score. Analyses were performed in age-matched normal coronary arteries (NCA) and CAD groups. Linear and logistic regression analyses were used for the multivariate analyses of independent variables associated with hair greying. RESULTS: The CVRFs were higher in CAD group. Hair whitening score (2.7 +/- 1.3 vs. 3.3 +/- 1.2, p=0.002), hair losing score (1.2 +/- 0.9 vs. 1.5 +/ 1.0, p=0.038) and xanthelasma rate (24% vs. 45%, p=0.013) were also significantly different between NCA and CAD groups. Age (p<0001), Gensini score (p<0.001) and coronary severity score (p=0.001) were higher in the categories of increased HWS. In multiple logistic regression analysis, only diabetes mellitus (OR: 3.240, 95% CI: [1.017-10.319], p=0.047), low-density lipoprotein cholesterol, (OR: 1.014, 95%CI: [1.001-1.027], p=0.029) and HWS (OR: 1.513, 95% CI: [1.054-2.173], p=0.025) were independently related to presence of CAD. Age (p<0.001), family history of CAD (p=0.004), hyperlipidemia (p=0.02) and serum creatinine levels (p=0.019) were found as independent predictors of hair graying. CONCLUSION: In our study, we found that the degree of gray/white hairs is related to extent of CAD. Our findings also suggested that hair graying is a risk marker for CAD independent of age and other traditional risk factors. Biological age may be important in determining total risk of patients. During assessment of cumulative CVRF effects on human body, presence of biological aging signs may be useful in identifying individuals with increased risk of cardiovascular disease. PMID- 22677403 TI - Biological aging and coronary artery disease. PMID- 22677404 TI - Effect of termination of the left anterior descending coronary artery (wrapped or non-wrapped property) on tissue Doppler echocardiography findings in patients with anterior myocardial infarction: an observational study. AB - OBJECTIVE: We aimed to evaluate effect of termination property of left anterior descending (LAD) on tissue Doppler echocardiography (TDE) parameters in patients experiencing their first anterior myocardial infarction (AMI) who had undergone successful primary percutaneous coronary intervention (PCI). METHODS: A prospective, cross-sectional observational study was performed. Eighty-four patients were enrolled in the study. Echocardiography was performed during the first three days of AMI. Conventional TDE measurements were obtained from right ventricular (RV) and four left ventricular (LV) walls: for the systolic function mitral annular TDE systolic velocity - Sm, for diastolic function - mitral annular TDE early and late diastolic velocities - Em, Am, transmitral early and late diastolic velocities ratio - E/A, and combined systolic and diastolic function - myocardial performance index (MPI). Coronary arteries were evaluated and patients were divided into two groups (non-wrapped LAD and wrapped LAD) according to the termination properties. Student-t, Mann-Whitney U and Chi-square tests, bivariate Pearson and Spearman correlation analyses were used for statistical analysis. RESULTS: Baseline characteristics and conventional echocardiographic parameters of the patients were similar. There was a statistically significant difference for the anterior wall Sm parameter, whereas there was no substantial difference for Em, Am and MPI values. The anterior wall Sm was more affected in patients with non wrapped LAD than in patients with wrapped LAD (6.70 +/- 1.66 and 7.44 +/- 1.66 cm/s; p=0.036,).The anterior Sm parameter was uniquely correlated with LAD termination status when compared with other independent parameters (r=0.236, p=0.036). CONCLUSION: We showed that termination of LAD is important for the anterior wall systolic functions in the early stage of AMI treated successfully. PMID- 22677405 TI - Assessment of agreement between transthoracic and transesophageal echocardiography techniques for left ventricular longitudinal deformation imaging and conventional Doppler parameters estimation: a cross-sectional study. AB - OBJECTIVE: Studies investigating the comparison and interchangeability of transthoracic (TTE) and transesophageal echocardiography (TEE) regarding left ventricular (LV) systolic and diastolic function are limited. Therefore, in this study, we aimed to investigate agreement between TTE and TEE in the assessment of LV systolic functions by longitudinal myocardial deformation imaging (strain-S and strain rate-Sr) and LV diastolic functions by conventional Doppler parameters. METHODS: Thirty-five patients underwent a clinically indicated cross sectional study on agreement between two methods. All the patients underwent TEE right after TTE. From both TTE and TEE Doppler parameters such as early and late diastolic velocities (E, A, E' and A') deceleration time (DT), averaged mitral annular systolic velocity (Sm), isovolumic relaxation time (IVRT), isovolumic contraction time (IVCT), ejection time (ET), myocardial performance index (MPI) and longitudinal deformation imaging parameters (S, Sr) and systolic velocities were recorded. Agreement between TTE and TEE were evaluated by Bland-Altman analysis. RESULTS: Bland-Altman analysis showed good agreement between TEE and TTE in terms of E, A, DT, E', A', IVRT, IVCT, ET and MPI measurements. However, there was poor agreement in segmental systolic velocities and segmental Sr parameters assessed by TTE and TEE. Besides, septal wall segmental S analysis showed a better agreement than lateral wall segmental analysis between TTE and TEE recordings. CONCLUSION: TTE and TEE conventional Doppler parameters are compatible in the assessment of LV diastolic function; however, agreement was poor in longitudinal deformation parameters that have been used in the quantitative assessment of LV systolic function between two methods and cannot be used interchangeably. PMID- 22677406 TI - Assessment of tissue Doppler parameters via transesophageal echocardiography: how necessary? PMID- 22677407 TI - Decreased aortic root elasticity-as a novel systemic manifestation of the pseudoexfoliation syndrome: an observational study. AB - OBJECTIVE: To assess the aortic root function in patients with pseudoexfoliation syndrome (PEXS). METHODS: In this case- controlled observational study, aortic root function in 31 PEXS patients (mean age 71 +/- 9 years) and 29 controls of similar ages (mean age 69 +/- 9 years) were evaluated by M-mode transthoracic echocardiography. Aortic cross-sectional compliance (CSC), Peterson's elastic modulus (index beta), aortic stiffness index (ASI) and aortic root distensibility (ARD) were calculated by M-mode echocardiography to evaluate the aortic root function. The findings of two groups of patients were compared by Mann-Whitney U test. RESULTS: The CSC and ARD were significantly decreased in patients with PEXS. The CSC was 12.2 +/- 6.3 cm2/mmHg in patients with PEXS and 17.5 +/- 11.6 cm2/mmHg in the control group (p=0.015). The ARD was 1.56 +/- 0.80 cm2/dyne in patients with PEXS and 2.23 +/- 1.48 cm2/dyne in the control group (p=0.021). The other two indices of aortic root function were not significantly different between the two groups. CONCLUSION: Aortic root function decreases in patients with PEXS. PEXS may be regarded as a risk factor for cardiovascular and cerebrovascular events. PMID- 22677408 TI - Is pseudoexfoliation syndrome a risk factor for cardiovascular diseases? PMID- 22677409 TI - In vitro effects of ascorbic acid and beta-glycerophosphate on human gingival fibroblast cells. AB - Ascorbic acid (AA) and beta-glycerophosphate (betaG) are considered in vitro osteogenic factors important to the differentiation of osteoblastic progenitor and dental pulp cells into mineralized tissue-forming cells. So, the present study investigated in vitro if these mineralizing inducible factors (AA and betaG) could influence differentiation of human gingival fibroblasts when compared with human pulp cells and osteogenic cells derived from rat calvaria cultured. The expression of osteopontin (OPN) and osteoadherin (OSAD) was analyzed by indirect immunofluorescence, immunocytochemistry as well as Western blotting. In addition, the main ultrastructural aspects were also investigated. No mineralized matrix formation occurred on gingival fibroblasts induced with AA+betaG. On these cells, no expression of OPN and OSAD was observed when compared with pulp cells, pulp cells induced with AA+betaG as well as osteogenic cells. Ultrastructure analysis additionally showed that gingival fibroblasts exhibited typical fibroblast morphology with no nodule formation. The present findings showed that AA and betaG could not promote a mineralized cell differentiation of human gingival fibroblasts and confirm that human dental pulp cells, as the osteogenic cells, are capable to form a mineralized extracellular. PMID- 22677411 TI - High-performance liquid chromatography coupled to mass spectrometry methodology for analyzing site-specific N-glycosylation patterns. AB - Analysis of protein glycosylation is a major challenge in biochemistry, here we present a nano-UHPLC-MS(MS) based methodology, which is suitable to determine site-specific N-glycosylation patterns. A few pmol glycoprotein is sufficient to determine glycosylation patterns (which opens the way for biomedical applications) and requires at least two separate chromatographic runs. One is using tandem mass spectrometry (for structure identification); the other single stage MS mode (for semi-quantitation). Analysis relies heavily on data processing. The previously developed GlycoMiner algorithm and software was used to identify glycopeptides in MS/MS spectra. We have developed a new algorithm and software (GlycoPattern), which evaluates single stage mass spectra, both in terms of glycopeptide identification (for minor glycoforms) and semi-quantitation. Identification of glycopeptide structures based on MS/MS analysis has a false positive rate of 1%. Minor glycoforms (when sensitivity is insufficient to obtain an MS/MS spectrum) can be identified in single stage MS using GlycoPattern; but in such a case the false positive rate is increased to 5%. Glycosylation is studied at the glycopeptide level (i.e. following proteolytic digestion). This way the sugar chains can be unequivocally assigned to a given glycosylation site (site-specific glycosylation pattern). Glycopeptide analysis has the further advantage that protein-specific glycosylation patterns can be identified in complex mixtures and not only in purified samples. This opens the way for medium high throughput analysis of glycosylation. Specific examples of site-specific glycosylation patterns of alpha-1-acid glycoprotein, haptoglobin and on a therapeutic monoclonal antibody, Infliximab are also discussed. PMID- 22677412 TI - In situ synthesis of twelve dialkyltartrate-boric acid complexes and two polyols boric acid complexes and their applications as chiral ion-pair selectors in nonaqueous capillary electrophoresis. AB - In this paper, twelve dialkyltartrate-boric acid complexes and two polyols-boric acid complexes were in situ synthesized by the reaction of different dialkyltartrates or polyols with boric acid in methanol containing triethylamine. All of the twelve dialkyltartrate-boric acid complexes were found to have relatively good chiral separation performance in nonaqueous capillary electrophoresis (NACE). Their chiral recognition effects in terms of both enantioselectivity (alpha) and resolution (R(s)) were similar when the number of carbon atoms was below six in the alkyl group of alcohol moiety. The dialkyltartrates containing alkyl groups of different structures but the same number of carbon atoms, i.e. one of straight chain and one of branched chain, also provided similar chiral recognition effects. Furthermore, it was demonstrated for the first time that two methanol insoluble polyols, D-mannitol and D-sorbitol, could react with boric acid to prepare chiral ion-pair selectors using methanol as the solvent medium. PMID- 22677413 TI - Strong ion exchange in centrifugal partition extraction (SIX-CPE): effect of partition cell design and dimensions on purification process efficiency. AB - The aim of this article was to evaluate the influence of the column design of a hydrostatic support-free liquid-liquid chromatography device on the process efficiency when the strong ion-exchange (SIX) development mode is used. The purification of p-hydroxybenzylglucosinolate (sinalbin) from a crude aqueous extract of white mustard seeds (Sinapis alba L.) was achieved on two types of devices: a centrifugal partition chromatograph (CPC) and a centrifugal partition extractor (CPE). They differ in the number, volume and geometry of their partition cells. The SIX-CPE process was evaluated in terms of productivity and sinalbin purification capability as compared to previously optimized SIX-CPC protocols that were carried out on columns of 200 mL and 5700 mL inner volume, respectively. The objective was to determine whether the decrease in partition cell number, the increase in their volume and the use of a "twin cell" design would induce a significant increase in productivity by applying higher mobile phase flow rate while maintaining a constant separation quality. 4.6g of sinalbin (92% recovery) were isolated from 25 g of a crude white mustard seed extract, in only 32 min and with a purity of 94.7%, thus corresponding to a productivity of 28 g per hour and per liter of column volume (g/h/LV(c)). Therefore, the SIX-CPE process demonstrates promising industrial technology transfer perspectives for the large-scale isolation of ionized natural products. PMID- 22677414 TI - Retention divergence of terpenes with porous graphitized carbon and C18 stationary phases. AB - The significant divergence between the retention of 16 terpene standards on porous graphitized carbon (PGC) and C18 packing materials are illustrated. The PGC surface is shown to provide a selectivity toward shape, polarity, and structure that is not afforded by the C18 surface. This observation is illustrated by plots of the retention factors similar to those typically used to represent 2D-HPLC separations. A geometric approach to factor analysis was used to measure the separation divergence together with the selectivity and the product selectivity factors of closely related species. When a methanol mobile phase was used with the PGC surface, a large fraction of the separation space could be utilized. That is further reflected by a spreading angle of 80.3 degrees . The PGC material was also successful at resolving structural isomers where the C18 phase was not. It was also found that the choice of the mobile phase is important when using this material. A much larger degree of space utilization was seen with methanol than with acetonitrile that displayed a spreading angle of only 40.8 degrees . PMID- 22677415 TI - Influence of dietary fatty acids on muscle fatty acid composition and expression levels of Delta6 desaturase-like and Elovl5-like elongase in common carp (Cyprinus carpio var. Jian). AB - The effects of dietary fatty acids on muscle fatty acid composition and liver expression levels of Delta6 desaturase-like and Elovl5-like elongase were investigated in common carp (Cyprinus carpio var. Jian). Two Delta6 desaturase like cDNAs (Fad6-a and Fad6-b) and two Elovl5-like elongase (Elovl5-a and Elovl5 b) cDNAs were cloned. Juvenile carp were fed three semi-purified diets (D1-3) for 6 weeks with different lipid sources: D1, fish oil with high highly unsaturated fatty acids (HUFAs); D2, corn oil with high linoleic acid (LA), but no HUFAs; and D3, linseed oil with high alpha-linolenic acid (LNA), but no HUFAs. Comparing muscle fatty acids among fish fed D1-3, the content of LA and arachidonic acid (AA) in common carp fed D2 and the content of LNA, EPA and DHA in common carp fed D3 were higher than initial levels (P<0.05), respectively. The liver transcript levels of Fad6-a and Elovl5-a in fish fed D2 and D3 were higher than initial levels (P<0.05), but Fad6-b and Elovl5-b levels were seldom affected by the diets. The dietary fatty acids affect the muscle fatty acid composition and the liver Fad6-a and Elovl5-a gene expression levels in common carp, and further studies should be undertaken. PMID- 22677417 TI - Improved physical stability and injectability of non-aqueous in situ PLGA microparticle forming emulsions. AB - The goal of this study was to obtain physically stable non-aqueous in situ forming microparticle (ISM) emulsions capable of forming biodegradable microparticles upon injection. ISM emulsions consist of a biocompatible organic PLGA solution dispersed in a continuous oil phase prepared in a two syringe/connector system prior to administration. A variety of parenteral approved excipients were tested for a stability-enhancing effect and possible stabilization mechanisms evaluated. Glycerol monostearate (GMS) showed superior stabilizing potential prolonging the emulsion stability from a few minutes to more than 12h. Flow behavior analysis, differential scanning calorimetry, polarized light- and Cryo-electron microscopy revealed, that the stabilization was caused by an immediate, more than 5-fold viscosity increase in the continuous phase after emulsification and by a stabilized interface through a liquid crystalline GMS layer around the polymer solution droplets. Despite the viscosity increase the injectability of the stabilized ISM emulsion was improved by about 30% compared to the corresponding highly viscous PLGA solution (in situ implant) due to a pronounced shear thinning of the GMS containing oil phase. The injectability improvement allows a faster administration or enables the use of thinner needles and hence reduced patient discomfort. PMID- 22677416 TI - Preparation of medicines for children - a hierarchy of classification. AB - There is some confusion about the types of paediatric pharmaceutical preparation (in a regulatory and pharmaceutical development context) that are acceptable for approval by medicines regulators. Some of the confusion relates to terminology which may mean different things to different stakeholders. It may not always be possible to provide authorised, commercially manufactured, age appropriate, ready to-administer preparations. In terms of assurance of quality and bioavailability there is a continuum from this ideal through intermediate products through authorised compounding and manipulation of commercial dosage forms to ad hoc compounding using only the skills and experience of the individual pharmacist. Additionally, it is widely known that caregivers may manipulate medicines at home, for example by segmenting tablets and by addition to foods or liquids. The first intent of the manufacturer should be to provide for children an age appropriate, ready-to-administer preparation which is commercially manufactured and approved by the competent authorities. However, there will still be a place for providing other age appropriate preparations such as approved products that are 'intermediates' requiring reconstitution before use, or instructions for compounding or manipulation of a dosage form. If compounding or manipulation is likely to be required it is preferable that data are generated by Industry, approved by the competent authorities and provided in the Summary of Product Characteristics (SmPC). It is acknowledged however, that ad hoc compounding or manipulation may also take place in certain circumstances such as logistical difficulties or to satisfy the needs of the child who does not find the authorised product to be 'age appropriate'. This paper explores compounding and manipulation of medicines in relation to approval by medicines regulators and non approved preparation to fulfil the needs of the individual patient. Definitions are proposed to provide a hierarchical classification based on assurances of quality and bioavailability. PMID- 22677418 TI - Liquisolid technique to enhance and to sustain griseofulvin dissolution: effect of choice of non-volatile liquid vehicles. AB - Liquisolid systems were originally designed to enhance dissolution of hydrophobic drugs. Recently, the same technique was explored to control drug release via hydrophobic carriers. This work aimed to study the effects of different liquid vehicles on release characteristics of griseofulvin as a model hydrophobic drug. Fast dissolution tablets were prepared using three different non-ionic surfactants namely Cremophor((r))EL, Synperonic((r))PE/L61 and CapryolTM 90, on the contrary Kollicoat((r))SR 30D was used for production of grieseofulvin sustained release formulations. Avicel((r)) PH102 and Cab-O-Sil((r)) M5 were used as carrier and coat materials, respectively. The effect of formulation parameters, such as drug concentration and carrier to coat ratio, on enhancing drug dissolution was explored. Drug concentrations of 20% and 40% (w/w), and R values (carrier to coat ratio) of 10 and 20 were used. The mathematical model was utilized to formulate liquisolid powder systems. All fast release liquisolid formulations showed higher percentage drug dissolution efficiency (%DE) than conventional directly compacted tablets. Cremophor((r))EL showed the best dissolution enhancement with %DE of about 90%, compared to only 23% for conventional tablets; DSC data suggested loss of griseofulvin crystallinity and thermal behavior. Kollicoat((r)) SR 30D retarded the drug release even in the presence of hydrophilic carrier; DSC data suggested that only small fraction of the drug was present in the molecular state within the system. The used liquisolid vehicles showed promise to enhance and to control (depend on the choice of the liquid vehicle) the release of griseofulvin from liquisolid compacts. PMID- 22677419 TI - Spatial incidence of dengue infections in Queensland, Australia - reply. PMID- 22677420 TI - CD11b+ bone marrow-derived monocytes are the major leukocyte subset responsible for retinal capillary leukostasis in experimental diabetes in mouse and express high levels of CCR5 in the circulation. AB - We investigated the phenotype of cells involved in leukostasis in the early stages of streptozotocin-induced diabetes in mice by direct observation and by adoptive transfer of calcein-AM-labeled bone marrow-derived leukocytes from syngeneic mice. Retinal whole mounts, confocal microscopy, and flow cytometry ex vivo and scanning laser ophthalmoscopy in vivo were used. Leukostasis in vivo and ex vivo in retinal capillaries was increased after 2 weeks of diabetes (Hb A(1c), 14.2 +/- 1.2) when either donor or recipient mice were diabetic. Maximum leukostasis occurred when both donor and recipient were diabetic. CD11b(+), but not Gr1(+), cells were preferentially entrapped in retinal vessels (fivefold increase compared with nondiabetic mice). In diabetic mice, circulating CD11b(+) cells expressed high levels of CCR5 (P = 0.04), whereas spleen (P = 0.0001) and retinal (P = 0.05) cells expressed increased levels of the fractalkine chemokine receptor. Rosuvastatin treatment prevented leukostasis when both recipient and donor were treated but not when donor mice only were treated. This effect was blocked by treatment with mevalonate. We conclude that leukostasis in early diabetic retinopathy involves activated CCR5(+)CD11b(+) myeloid cells (presumed monocytes). However, leukostasis also requires diabetes-induced changes in the endothelium, because statin therapy prevented leukostasis only when recipient mice were treated. The up-regulation of the HMG-CoA reductase pathway in the endothelium is the major metabolic dysregulation promoting leukostasis. PMID- 22677421 TI - Co-exposure to cigarette smoke and alcohol decreases airway epithelial cell cilia beating in a protein kinase Cepsilon-dependent manner. AB - Alcohol use disorders are associated with increased lung infections and exacerbations of chronic lung diseases. Whereas the effects of cigarette smoke are well recognized, the interplay of smoke and alcohol in modulating lung diseases is not clear. Because innate lung defense is mechanically maintained by airway cilia action and protein kinase C (PKC)-activating agents slow ciliary beat frequency (CBF), we hypothesized that the combination of smoke and alcohol would decrease CBF in a PKC-dependent manner. Primary ciliated bronchial epithelial cells were exposed to 5% cigarette smoke extract plus100 mmol/L ethanol for up to 24 hours and assayed for CBF and PKCepsilon. Smoke and alcohol co-exposure activated PKCepsilon by 1 hour and decreased both CBF and total number of beating cilia by 6 hours. A specific activator of PKCepsilon, DCP-LA, slowed CBF after maximal PKCepsilon activation. Interestingly, activation of PKCepsilon by smoke and alcohol was only observed in ciliated cells, not basal bronchial epithelium. In precision-cut mouse lung slices treated with smoke and alcohol, PKCepsilon activation preceded CBF slowing. Correspondingly, increased PKCepsilon activity and cilia slowing were only observed in mice co-exposed to smoke and alcohol, regardless of the sequence of the combination exposure. No decreases in CBF were observed in PKCepsilon knockout mice co-exposed to smoke and alcohol. These data identify PKCepsilon as a key regulator of cilia slowing in response to combined smoke and alcohol-induced lung injury. PMID- 22677422 TI - Toward homeostasis: regulatory dendritic cells from the bone marrow of mice with inflammation of the airways and peritoneal cavity. AB - Inflammatory mediators from peripheral tissues may control dendritic cell (DC) development in the bone marrow. In this study, DCs (CD11c(+) cells) differentiated from the bone marrow of mice with inflammation of the airways, or the peritoneal cavity had poor priming ability resulting in reduced, long-lived responses to that antigen in vivo. This indicates enhancement of regulatory mechanisms of immune responses through a peripheral tissue-bone marrow axis. If CD11c(+) cells, expanded from the bone marrow of mice with tissue inflammation were antigen pre-loaded and injected into mice already sensitized to that antigen, then subsequent contact hypersensitivity responses were significantly reduced. The effects of inflammation were imprinted in vivo and were independent of in vitro culture conditions for DC differentiation. The effect of tissue inflammation on the bone marrow DC precursors was not detected in mice treated subcutaneously with slow-release indomethacin pellets, suggesting a role for prostanoids, including prostaglandin E(2), in differentiation of regulatory CD11c(+) cells from bone marrow. Our study represents an important homeostatic process with potential for therapeutic use in the future. PMID- 22677424 TI - Rufinamide efficacy and safety as adjunctive treatment in children with focal drug resistant epilepsy: the first Italian prospective study. AB - Rufinamide is a new antiepileptic drug approved as add-on treatment in Lennox Gastaut syndrome from the age of 4 years, and for the treatment of focal seizures in adults and adolescents. The aim of this prospective study was to evaluate the safety and efficacy of add-on Rufinamide in the treatment of childhood focal drug resistant epilepsy. We recruited 70 patients for a prospective, add-on, open label study. Inclusion criteria were: 3 years of age or more; focal drug resistant epilepsy despite the use of three previous AEDs; use of at least one other AED, but no more than three at baseline; more than one seizure per month in the previous 6 months. Rufinamide efficacy was observed up to 12 months of follow up, with a total responder rate of 38.57%. We found the best results in focal epilepsies due to structural/metabolic etiology (42.6%). The responder rate was similar for focal seizures with secondary generalization, simple focal seizures other than myoclonic jerks, and complex partial seizures. Response to Rufinamide was not related to the age. Our experience suggests that Rufinamide can be effective in reducing focal seizure frequency in children with drug resistant epilepsy, and that it can be considered as a safe drug. PMID- 22677426 TI - Retinal nerve fiber layer imaging with spectral-domain optical coherence tomography: patterns of retinal nerve fiber layer progression. AB - OBJECTIVE: To examine the use of the retinal nerve fiber layer (RNFL) thickness map generated by a spectral-domain optical coherence tomography (OCT) to detect RNFL progression and identify the pattern of progressive changes of RNFL defects in glaucoma. DESIGN: Prospective, longitudinal study. PARTICIPANTS: One hundred eighty-six eyes of 103 glaucoma patients. METHODS: Patients were followed at 4 month intervals for >= 36 months for RNFL imaging and visual field examination. Both eyes were imaged by the Cirrus HD-OCT (Carl Zeiss Meditec Inc., Dublin, CA) and had visual field testing at the same visits. We defined RNFL progression by Guided Progression Analysis (Carl Zeiss Meditec) of serial RNFL thickness maps. The pattern of RNFL progression was evaluated by comparing the baseline RNFL thickness deviation map and the RNFL thickness change map. Visual field progression was defined by trend analysis of visual field index and event analysis based on the Early Manifest Glaucoma Trial criteria. MAIN OUTCOME MEASURES: The presence and the pattern of RNFL progression. RESULTS: A total of 2135 OCT images were reviewed. Twenty-eight eyes (15.1%) from 24 patients (23.3%) had RNFL progression detected by RNFL thickness map analysis. Three RNFL progression patterns were observed: (1) widening of RNFL defects (24 eyes, 85.7%), (2) deepening of RNFL defects (2 eyes, 7.1%, both had concomitant widening of RNFL defects), and (3) development of new RNFL defects (5 eyes, 17.9%). The inferotemporal meridian (324 degrees -336 degrees ) 2.0 mm away from the optic disc center was the most frequent location where RNFL progression was detected. Thirteen eyes (46.4%) had concomitant visual field progression; 61.5% (n = 8) of these had RNFL progression that preceded or occurred concurrently with visual field progression. Forty-two eyes from 37 patients (22.6%) had visual field progression by trend and/or event analyses without progression in the RNFL thickness map. CONCLUSIONS: Analysis of serial RNFL thickness maps generated by the spectral-domain OCT facilitates the detection of RNFL progression in glaucoma. PMID- 22677425 TI - Blindness and visual impairment in an urban West African population: the Tema Eye Survey. AB - OBJECTIVE: To determine the prevalence, causes, and risk factors of blindness and visual impairment among persons aged 40 years or older residing in an urban West African location. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: A total of 5603 participants residing in Tema, Ghana. METHODS: Proportionate random cluster sampling was used to select participants aged 40 years or older living in the city of Tema. Presenting distance visual acuity (VA) was measured at 4 and 1 m using a reduced logarithm of the minimum angle of resolution tumbling E chart and then with trial frame based on autorefraction. A screening examination was performed in the field on all participants. Complete clinical examination by an ophthalmologist was performed on participants with best corrected visual acuity (BCVA) <20/40 or failure of any screening test. MAIN OUTCOME MEASURES: Age- and gender-specific prevalence, causes, and risk factors for blindness (VA of <20/400 in the better eye, World Health Organization definition) and visual impairment (VA of <20/40 in the better eye). RESULTS: A total of 6806 eligible participants were identified, of whom 5603 (82.3%) participated in the study. The mean age (+/- standard deviation) of participants was 52.7 +/- 1 0.9 years. The prevalence of visual impairment and blindness was 17.1% and 1.2%, respectively. After refraction and spectacle correction, the prevalence of visual impairment and blindness decreased to 6.7% and 0.75%, respectively, suggesting that refractive error is the major correctable cause of visual impairment and blindness in this population. Of 65 subjects with a VA <20/400, 22 (34%) were correctable with refraction, 21 to the level of visual impairment and 1 to normal. The remaining 43 patients (66%) had underlying pathology (cataract in 19, glaucoma in 9, nonglaucomatous optic neuropathy in 3, corneal opacities in 3, retinal disease in 3, and undetermined in 5) that prevented refractive correction. Increased age was a significant risk factor for blindness and visual impairment. CONCLUSIONS: There is a high prevalence of blindness and visual impairment among those aged >= 40 years in Tema, Ghana, West Africa. Refractive error is a major cause of blindness and visual impairment in this population, followed by cataract, glaucoma, and corneal disease. PMID- 22677423 TI - Neonatal oxygen increases sensitivity to influenza A virus infection in adult mice by suppressing epithelial expression of Ear1. AB - Oxygen exposure in premature infants is a major risk factor for bronchopulmonary dysplasia and can impair the host response to respiratory viral infections later in life. Similarly, adult mice exposed to hyperoxia as neonates display alveolar simplification associated with a reduced number of alveolar epithelial type II cells and exhibit persistent inflammation, fibrosis, and mortality when infected with influenza A virus. Because type II cells participate in innate immunity and alveolar repair, their loss may contribute to oxygen-mediated sensitivity to viral infection. A genomewide screening of type II cells identified eosinophil associated RNase 1 (Ear1). Ear1 was also detected in airway epithelium and was reduced in lungs of mice exposed to neonatal hyperoxia. Electroporation-mediated gene delivery of Ear1 to the lung before infection successfully reduced viral replication and leukocyte recruitment during infection. It also diminished the enhanced morbidity and mortality attributed to neonatal hyperoxia. These findings demonstrate that novel epithelial expression of Ear1 functions to limit influenza A virus infection, and its loss contributes to oxygen-associated epithelial injury and fibrosis after infection. People born prematurely may have defects in epithelial innate immunity that increase their risk for respiratory viral infections. PMID- 22677427 TI - Hepatoid pancoast tumor. A case report and review of the literature. AB - A 48-year-old male patient presented with a Pancoast tumor of the right lung and a serum alpha-fetoprotein (alphaFP) at 39,000 ng/ml. Alpha-fetoprotein is a tumor marker found elevated in patients with hepatocellular carcinoma (HCC), germ cell or stromal tumors of the ovary and nonseminomatous testicular cancer. Occasionally, this tumor marker may rise in non-neoplastic conditions such as cirrhosis and hepatitis and only exceptionally in rare cancers with hepatoid differentiation. We present our case report and review the English literature for alphaFP-producing lung carcinomas. To the best of our knowledge this is the first report in the literature of an alphaFP producing Pancoast tumor. PMID- 22677428 TI - Prophylactic cranial irradiation in patients with small cell lung cancer. A retrospective study of recurrence, survival and morbidity. AB - BACKGROUND: Prophylactic cerebral irradiation (PCI) is a standard treatment for all small cell lung cancer (SCLC) patients with response to chemotherapy. The aims of this study were: to evaluate patients undergoing PCI with regard to cerebral recurrence rate, site of recurrence, and overall survival (OS) and to investigate the influence of steroid dose on acute toxicity. MATERIALS AND METHODS: From 2007 to 2010 a total of 118 consecutive patients underwent PCI (25 Gray in 10 fractions). In total, 114/118 received full PCI dose, all 118 were included in the study. Data were analyzed retrospectively with regard to disease stage, treatment, date of PCI, steroid dose during PCI, toxicity, time to recurrence, site of recurrence and time of death. The median follow up time was 16.6 months (range 3-54 months). RESULTS: Of the 118 patients undergoing PCI, 74 had limited disease (LD-SCLC) and 44 had extensive disease (ED-SCLC). The median age was 65 years (range 46-80 years). The median overall survival of all patients from the time of diagnosis was 16.0 months (CI 95% 13.0-19.0), in LD-SCLC it was 24.0 months (CI 95% 19.6-28.3), and in ED-SCLC it was 12.0 months (CI 95% 9.6 14.4). Twenty-one patients (17.8%) were diagnosed with cerebral recurrence. Five of these presented with metastatic disease within the limbic system. Of these five patients, four had miliary cerebral disease and one had non-oligometastatic disease. The time from PCI to cerebral recurrence ranged from 4 to 27 months. Prednisolone administration varied from 0 to 100 mg/day. Forty-eight patients were not treated with steroids, 64.6% of these patients reported acute toxicity. Of the 36 patients receiving 50 mg prednisolone, only 22.2% had side effects. The most common symptoms during PCI were nausea and headache. CONCLUSIONS: Twenty-one patients out of 118 developed brain metastases after PCI: five of the twenty-one had metastases located in the limbic system. The study showed that prophylactic steroid use might reduce acute toxicity to PCI. Survival data and recurrence rates are comparable to other clinical studies. PMID- 22677429 TI - Efficacy of epidermal growth factor receptor tyrosine kinase inhibitors for brain metastasis in non-small cell lung cancer patients harboring either exon 19 or 21 mutation. AB - Non-small cell lung cancer (NSCLC) harboring an activating epidermal growth factor receptor (EGFR) mutation shows good and rapid response to EGFR tyrosine kinase inhibitors (TKIs). We prospectively evaluated the efficacy of EGFR TKI for metastatic brain tumors in NSCLC patients harboring EGFR mutation. This was an open-label, single-institution, phase II study. Patients diagnosed with NSCLC harboring EGFR mutation and measurable metastatic brain tumors were eligible. They received either erlotinib or gefitinib once a day. Out of total 28 patients enrolled, 23 patients (83%) showed a partial response (PR) and 3 patients (11%) did stable disease (SD), giving a disease control rate of 93%. Median progression free survival (PFS) and overall survival (OS) were 6.6 months (95% CI, 3.8-9.3 months) and 15.9 months (95% CI, 7.2-24.6 months), respectively. There was no difference in PFS and OS according to EGFR TKIs used. After discontinuation of the treatment, 14 patients (50%) received local therapy for metastatic brain tumors during their disease course, either whole brain radiotherapy or radiosurgery, giving a local therapy-free interval of 12.6 months (95% CI, 7.6 17.6 months). EGFR TKI therapy might be the treatment of choice for metastatic brain tumors in NSCLC patients harboring an activating EGFR mutation. PMID- 22677430 TI - Phosphatidylserine-expressing cell by-products in transfusion: A pro-inflammatory or an anti-inflammatory effect? AB - Labile blood products contain phosphatidylserine-expressing cell dusts, including apoptotic cells and microparticles. These cell by-products are produced during blood product process or storage and derived from the cells of interest that exert a therapeutic effect (red blood cells or platelets). Alternatively, phosphatidylserine-expressing cell dusts may also derived from contaminating cells, such as leukocytes, or may be already present in plasma, such as platelet derived microparticles. These cell by-products present in labile blood products can be responsible for transfusion-induced immunomodulation leading to either transfusion-related acute lung injury (TRALI) or increased occurrence of post transfusion infections or cancer relapse. In this review, we report data from the literature and our laboratory dealing with interactions between antigen presenting cells and phosphatidylserine-expressing cell dusts, including apoptotic leukocytes and blood cell-derived microparticles. Then, we discuss how these phosphatidylserine-expressing cell by-products may influence transfusion. PMID- 22677431 TI - A threshold model for the susceptibility to transfusion-related acute lung injury. AB - Transfusion-related acute lung injury (TRALI) is a serious, often life threatening pulmonary transfusion reaction characterized by non-cardiogenic lung oedema, hypoxemia and respiratory distress in temporal association with blood transfusion. The critical mechanism in TRALI is the sudden increase in permeability of the pulmonary endothelium and the subsequent, often extensive shift of fluid into the alveolae. The rapid clinical recovery seen in most patients makes it likely that this is a temporary phenomenon. Reactive oxygen species released by neutrophils or other cells are attractive candidate mediators of this process. There is experimental and clinical evidence that several pathways can induce barrier breakdown in TRALI, a concept known as the threshold model of TRALI. Surprisingly, neutrophils may not always be required. Other cells may play a role as multipliers or attenuators of TRALI, depending on recipient related and transfusion-related factors involved. This review will summarize recent findings on pathophysiology, with a focus on newly discovered or disenchanted recipient-related and transfusion-related risk factors for TRALI and will present the threshold model of TRALI as a unifying concept on how TRALI develops. PMID- 22677432 TI - Algorithm for codevelopment of new drug-predictive biomarker combinations: accounting for inter- and intrapatient tumor heterogeneity. PMID- 22677433 TI - Psychometric performance of the CushingQoL questionnaire in conditions of real clinical practice. AB - OBJECTIVE: To evaluate health-related quality of life (HRQoL) in Cushing's syndrome (CS) with the disease-generated CushingQoL questionnaire and to confirm its psychometric properties of test-retest reliability and sensitivity to change. DESIGN: Clinical practice conditions in a tertiary referral center. METHODS: The CushingQoL and EuroQoL questionnaires were administered at baseline and during follow-up and correlated with clinical parameters in 59 patients with CS. To check test-retest reliability, stable patients (either biochemically cured or with active hypercortisolism) were evaluated twice. To investigate sensitivity to change, new patients were evaluated at diagnosis and twice more following improvement after successful surgery. RESULTS: At baseline, patients with active disease scored lower (indicating worse HRQoL) than those cured on the CushingQoL (46 +/- 14 vs 58 +/- 20, P<0.05) but not on the EuroQoL-visual analog scale (VAS; 64 +/- 20 vs 70 +/- 16, P NS). Test-retest reliability of CushingQoL was confirmed in stable patients, both in the 'cured group' (intraclass correlation coefficient (ICC)=0.78, n=34) and in the 'active group' (ICC=0.66, n=14). Sensitivity to change was confirmed in the 'improvement group' (n=11), as the CushingQoL score increased 4 +/- 1.5 and 9 +/- 3 months after surgery (P<0.01 and <0.001 respectively); the EuroQoL-VAS only improved after 9 +/- 3 months (P<0.01). Effect sizes were 1.02 and 1.86 for CushingQoL at 4 +/- 1.5 and 9 +/- 3 months respectively. Finally, scores of both questionnaires were correlated (r=0.504; P<0.001). CONCLUSIONS: The CushingQoL questionnaire shows good test retest reliability and sensitivity to change in clinical practice conditions. PMID- 22677434 TI - Why two endothelins and two receptors for ovulation and luteal regulation? AB - The ovary is a dynamic organ that undergoes cyclic structural and functional changes. Structurally, the internal architecture of the ovary constantly changes as follicles grow, rupture and transform into corpora lutea in a cyclical manner. Functionally, a variety of regulatory ovarian hormones are sequentially produced, and eggs are periodically released. As a highly vascularized organ, the ovarian structures and functions change in response to external stimuli that include but are not limited to pituitary gonadotropins. Following stimulation, the ovary synthesizes and releases autocrine and paracrine signals that play unique roles in regulating its function. Recent studies have identified endothelins as local regulators in the ovary that modulate multiple cyclic events, such as follicle growth, steroidogenesis, oocyte maturation, ovulation, corpus luteum formation and luteolysis. Interestingly, in all mammalian species examined to date, a common observation has been made: the ovary produces two pharmacologically similar endothelins (ET-1 and ET-2) but expresses two functionally different endothelin receptors (ET(A) and ET(B)) that often give rise to opposite physiological outcomes following activation by an endothelin. In this review, the physiological significance of the presence of the two ligand-two receptor endothelin system in the ovary will be discussed. PMID- 22677435 TI - MicroRNA 16 enhances differentiation of human bone marrow mesenchymal stem cells in a cardiac niche toward myogenic phenotypes in vitro. AB - AIM: Upregulation of microRNA 16 (miR-16) contributed to the differentiation of human bone marrow mesenchymal stem cells (hMSCs) toward myogenic phenotypes in a cardiac niche, the present study aimed to determine the role of miR-16 in this process. MAIN METHODS: hMSCs and neonatal rat ventricular myocytes were co cultured indirectly in two chambers to set up a cardiac microenvironment (niche). miRNA expression profile in cardiac-niche-induced hMSCs was detected by miRNA microarray. Cardiac marker expression and cell cycle analysis were determined in different treatment hMSCs. Quantitative real-time PCR and Western blot were used to identify the expression of mRNA, mature miRNA and protein of interest. KEY FINDINGS: miRNA dysregulation was shown in hMSCs after cardiac niche induction. miR-16 was upregulated in cardiac-niche-induced hMSCs. Overexpression of miR-16 significantly increased G1-phase arrest of the cell cycle in hMSCs and enhanced the expression of cardiac marker genes, including GATA4, NK2-5, MEF2C and TNNI3. Differentiation-inducing factor 3 (DIF-3), a G0/G1 cell cycle arrest compound, was used to induce G1 phase arrest in cardiac-niche-induced hMSCs, and the expression of cardiac marker genes was up-regulated in DIF-3-treated hMSCs. The expression of CCND1, CCND2 and CDK6 was suppressed by miR-16 in hMSCs. CDK6, CCND1 or CCND2 knockdown resulted in G1 phase arrest in hMSCs and upregulation of cardiac marker gene expression in hMSCs in a cardiac niche. SIGNIFICANCE: miR-16 enhances G1 phase arrest in hMSCs, contributing to the differentiation of hMSCs toward myogenic phenotypes when in a cardiac niche. This mechanism provides a novel strategy for pre-modification of hMSCs before hMSC-based transplantation therapy for severe heart diseases. PMID- 22677436 TI - Amitriptyline converts non-responders into responders to low-frequency electroacupuncture-induced analgesia in rats. AB - AIMS: The purpose of this study was to examine whether the use of intraperitoneal or intrathecal amitriptyline combined with electroacupuncture modifies the tail flick reflex and incision pain in rats that normally do not have analgesia to electroacupuncture in the tail-flick test (non-responder rats). MAIN METHODS: Changes in the nociceptive threshold of intraperitoneal or intrathecal saline- or amitriptyline-treated non-responder rats were evaluated using the tail-flick or incision pain tests before, during and after a 20-min period of electroacupuncture, applied at 2 Hz to the Zusanli and Sanynjiao acupoints. Amitriptyline was used at doses of 0.8 mg/kg or 30 MUg/kg by intraperitoneal or intrathecal route, respectively. At these doses, amitriptyline has no effect against thermal or incision pain in rats. KEY FINDINGS: Rats selected as non responders to the analgesic effect of electroacupuncture 2 Hz in tail-flick and incision pain tests become responders after an intraperitoneal or intrathecal injection of amitriptyline. SIGNIFICANCE: Amitriptyline converts non-responder rats to rats that respond to electroacupuncture with analgesia in a model of thermal phasic pain and anti-hyperalgesia in a model of incision pain. PMID- 22677437 TI - Effectiveness of an online group course for depression in adolescents and young adults: a randomized trial. AB - BACKGROUND: Depression is a serious mental health problem, whose first onset is usually in adolescence. Online treatment may offer a solution for the current undertreatment of depression in youth. For adults with depressive symptoms, the effectiveness of Internet-based cognitive behavioral therapy has been demonstrated. This study is one of the first randomized controlled trials to investigate the effectiveness online depression treatment for young people with depressive complaints and the first to focus on an online group course. OBJECTIVE: To evaluate and discuss the effectiveness of a guided Web-based group course called Grip op Je Dip (Master Your Mood [MYM]), designed for young people aged 16 to 25 years with depressive symptoms, in comparison with a wait-listed control group. METHODS: We randomly assigned 244 young people with depressive symptoms to the online MYM course or to a waiting-list control condition. The primary outcome measure was treatment outcome after 3 months on the Center for Epidemiologic Studies Depression Scale. Secondary outcomes were anxiety (measured by the Hospital Anxiety and Depression Scale) and mastery (Mastery Scale). We studied the maintenance of effects in the MYM group 6 months after baseline. Missing data were imputed. RESULTS: The MYM group (n = 121) showed significantly greater improvement in depressive symptoms at 3 months than the control group (n = 123) (t(187 )= 6.62, P < .001), with a large between-group effect size of d = 0.94 (95% confidence interval [CI] 0.64-1.23). The MYM group also showed greater improvement in anxiety (t(187 )= 3.80, P < .001, d = 0.49, 95% CI 0.24-0.75) and mastery (t(187 )= 3.36, P = .001, d = 0.44, 95% CI 0.19-0.70). At 12 weeks, 56% (68/121) of the participants in the MYM group and 20% (24/123) in the control group showed reliable and clinically significant change. This between-group difference was significant (chi(2) (1 )= 35.0, P < .001) and yielded a number needed to treat of 2.7. Improvements in the MYM group were maintained at 6 months. A limitation is the infeasibility of comparing the 6-month outcomes of the MYM and control groups, as the controls had access to MYM after 3 months. CONCLUSIONS: The online group course MYM was effective in reducing depressive symptoms and anxiety and in increasing mastery in young people. These effects persisted in the MYM group at 6 months. PMID- 22677438 TI - Stabilization through precipitation in a system of colloidal iron(III) pyrophosphate salts. AB - The ionic strength of a solution decreases during the precipitation of an insoluble salt, which can cause an initially unstable colloidal system to stabilize during its formation. We show this effect in the precipitation and aging of colloidal iron(III) pyrophosphate, where we observe two distinct stages in the aggregation process. The first stage is the formation of nanoparticles that immediately aggregate into clusters with sizes on the order of 200 nm. In the second stage these clusters slowly grow in size but remain in dispersion for days, even months for dialyzed systems. Eventually these clusters become macroscopically large and sediment out of dispersion. Noting the clear instability of the nanoparticles, it is interesting to find two stages in their aggregation even without the use of additives such as surface active molecules. This is explained by accounting for the rapid decrease of ionic strength during precipitation, rendering the nanoparticles relatively stable when precipitation is complete. Calculating the interaction potentials for this scenario we find good agreement with the experimental observations. These results indicate that coupling of ionic strength to aggregation state can be significant and should be taken into account when considering colloidal stability of insoluble salts. PMID- 22677439 TI - Constructing honeycomb micropatterns on nonplanar substrates with high glass transition temperature polymers. AB - In Qiao's previous report, only star polymers with T(g) (glass transition temperature) below 48 degrees C were found forming homogeneous honeycomb coatings on the nonplanar substrates. The polymers with high T(g) are believed not able to duplicate nonplanar substrate due to their brittleness. This article presents a comprehensive study on the construction of macroporous polymeric films on various nonplanar substrates with static breath figure (BF) technique, using linear polymers with high T(g). Two kinds of linear polymers with high T(g), polystyrene b-poly(acrylic acid) and polystyrene without polar end groups, are employed to prepare 3-dimensional macroporous films on different nonplanar substrates. Scanning electronic microscopy views on the side wall in addition to views in plane prove that polymer films with BF array perfectly replicated the surface features of these substrates. The formation processes of macropores on these substrates are analyzed in detail, and it demonstrates that neither molecular topography nor T(g) of polymers is the critical factor contouring nonplanar substrate. A new hypothesis involving polymer plasticization and conformation during the solvent evaporation is formulated. PMID- 22677440 TI - A model for carbon nanotube-DNA hybrid using one-dimensional density of states. AB - A model for a carbon nanotube (CNT)-DNA hybrid embedded in an electrolyte solution is developed. The DNA charges are smeared out uniformly onto a cylindrical surface covering the CNT and the response of the CNT to the DNA charges is captured using the one-dimensional density of states (1D DOS) proposed by Mintmire et al. Coupled with the Debye-Huckel equation for the electrolyte, the expressions for the electric potential of the hybrid are obtained for both metallic and semiconducting CNT cores. For the surface charge density of the cylinder corresponding to the physically measured wrapping angles of a single stranded DNA around a CNT, the developed model predicts that the induced charges on a semiconducting CNT are about one order of magnitude smaller than the DNA charges, while the induced charges on a metallic CNT can be comparable in magnitude to the DNA charges. Because of this, the magnitude of the electric potential for a metallic CNT-DNA hybrid can be as much as approximately equal 30% smaller than that for a semiconducting one. This result can be used to explain the experiments on DNA-assisted CNT separation using ion exchange chromatography. PMID- 22677441 TI - Synthesis of cationic poly(4-vinylpyridine)-functionalized colloidal particles by emulsion polymerization with reactive block copolymer for protein adsorption. AB - We report here a novel protein sequestration method using polymeric colloidal particles prepared by emulsion polymerization with reactive block copolymers. Specifically, poly(4-vinyl-N-ethylpyridine bromide)-block-polymethylacrylate block copolymers were synthesized from reversible addition-fragmentation chain transfer polymerization and used as emulsifiers for emulsion polymerization of poly(4-vinyl-N-ethylpyridine bromide)-functionalized polymeric colloidal particles. The particles have high and stable zeta potentials when dispersed in solution, regardless of pH variations. As a result, the polymeric colloids demonstrate a high affinity for oppositely charged proteins, even though the isoelectric points of proteins may vary greatly. We show here that BSA can be sequestered highly efficiently with a maximum binding capacity (~900 mg/g). The adsorbed protein is easily released, and the polymeric colloids are regenerated after washing with a buffer solution of high ionic strength. These properties may prompt this type of novel macromolecule-functionalized colloids to be utilized for effective protein adsorption and separation. PMID- 22677443 TI - Neural controls of human hair growth: calcitonin gene-related peptide (CGRP) induces catagen. PMID- 22677442 TI - Neuroprotective effects of nimodipine and nifedipine in the NGF-differentiated PC12 cells exposed to oxygen-glucose deprivation or trophic withdrawal. AB - The goal of this study was to compare the neuroprotective properties of the L type Ca2+ channel blockers, nimodipine and nifedipine, using nerve growth factor (NGF)-differentiated PC12 neuronal cultures exposed to oxygen-glucose deprivation (OGD) and trophic withdrawal-induced cell death. Nimodipine (1-100 MUM) conferred 65+/-13% neuroprotection upon exposure to OGD and 35+/-6% neuroprotection towards different trophic withdrawal-induced cell death measured by lactate dehydrogenase and caspase 3 activities. The time window of nimodipine conferred neuroprotection was detected during the first 5h but not at longer OGD exposures. Nifedipine (1 100 MUM), to a lower potency than nimodipine, conferred 30-55+/-8% neuroprotection towards OGD in PC12 cells and 29+/-5% in rat hypocampal slices, and 10+/-3% neuroprotection at 100 MUM towards trophic withdrawal-induced PC12 cell death. The ability to demonstrate that nimodipine conferred neuroprotection in a narrow therapeutic time-window indicates that the OGD PC12 model mimics the in vivo models and therefore suitable for neuroprotective drug discovery and development. PMID- 22677444 TI - Analysis of the aetiology of diarrhoea in outpatients in 2007, Henan province, China. AB - The purpose of this study was to determine the aetiology of acute diarrhoea and improve knowledge of gastrointestinal pathogens in China. Faecal specimens from 1526 outpatients with diarrhoea were collected from 20 hospitals in Henan province and the prevalence of seven bacterial and five viral diarrhoeagenic pathogens were determined. Bacterial pathogens were recovered from 279/1526 (18.3%) stool specimens and viral pathogens were detected in 178/1526 (11.7%) stool specimens. The top five pathogenic species were diarrhoeagenic E. coli (n = 140, 9.2%), rotavirus (n = 79, 5.2%), Shigella spp. (n = 69, 4.5%), Salmonella spp. (n = 66, 4.3%) and norovirus (n = 56, 3.7%). The prevalence of pathogens showed correlation with age, season and clinical symptoms. Several dominant serotypes were identified in Shigella and Salmonella isolates, and high prevalence of multiple drug-resistant isolates was observed in both species. This important information will have a significant effect on public health policy development and resource prioritization practices. PMID- 22677447 TI - Nicotiflorin, rutin and chlorogenic acid: phenylpropanoids involved differently in quantitative resistance of potato tubers to biotrophic and necrotrophic pathogens. AB - Physiological and molecular mechanisms underlying quantitative resistance of plants to pathogens are still poorly understood, but could depend upon differences in the intensity or timing of general defense responses. This may be the case for the biosynthesis of phenolics which are known to increase after elicitation by pathogens. We thus tested the hypothesis that differences in quantitative resistance were related to differential induction of phenolics by pathogen-derived elicitors. Five potato cultivars (Solanum tuberosum, L.) spanning a range of quantitative resistance were treated with a concentrated culture filtrate (CCF) of Phytophthora infestans or purified lipopolysaccharides (LPS) from Pectobacterium atrosepticum. The kinetic of phenolics accumulation was followed and a set of typical phenolics was identified: chlorogenic acid, phenolamides and flavonols including rutin (quercetin-3-O-rutinoside) and nicotiflorin (kaempferol-3-O-rutinoside). Our results showed that CCF but not LPS induced differential accumulation of major phenolics among cultivars. Total phenolics were related with resistance to P. atrosepticum but not to P. infestans. However, nicotiflorin was inversely related with resistance to both pathogens. Rutin, but not nicotiflorin, inhibited pathogen growth in vitro at physiological concentrations. These data therefore suggest that (i) several phenolics are candidate markers for quantitative resistance in potato, (ii) some of these are pathogen specific although they are produced by a general defense pathway, (iii) resistance marker molecules do not necessarily have antimicrobial activity, and (iv) the final content of these target molecules-either constitutive or induced-is a better predictor of resistance than their inducibility by pathogen elicitors. PMID- 22677446 TI - Autophagy intersections with conventional and unconventional secretion in tissue development, remodeling and inflammation. AB - Autophagy is a cell biological process ubiquitous to all eukaryotic cells, often referred to as a catabolic, lysosomal degradative pathway. However, current studies in mammalian systems suggest that autophagy plays an unexpectedly broad biogenesis role in protein trafficking and secretion. Autophagy supports alternative trafficking pathways for delivery of integral membrane proteins to the plasma membrane and affects secretion, including the constitutive, regulated and unconventional secretion pathways. Autophagy-based unconventional secretion, termed here 'autosecretion', is one of the pathways enabling leaderless cytosolic proteins to exit the cell without entering the endoplasmic reticulum (ER)-to Golgi secretory pathway. In this review, we discuss the emerging underlying mechanisms of how autophagy affects different facets of secretion. We also describe the physiological roles of autosecretory cargos that are often associated with inflammatory processes and also play a role in the formation of specialized tissues and in tissue remodeling, expanding the immediate sphere of influence of autophagy from the intracellular to the extracellular space. PMID- 22677449 TI - Isolation and characterization of novel variants of BBI coding genes from the legume Lathyrus sativus. AB - A pool of twelve cDNA sequences coding for Bowman-Birk inhibitors (BBIs) was identified in the legume grass pea (Lathyrus sativus L.). The corresponding amino acid sequences showed a canonical first anti-trypsin domain, predicted according to the identity of the determinant residue P(1). A more variable second binding loop was observed allowing to identify three groups based on the identity of residue P(1): two groups (Ls_BBI_1 and Ls_BBI_2) carried a second reactive site specific for chymotrypsin, while a third group (Ls_BBI_3) was predicted to inhibit elastase. A fourth variant carrying an Asp in the P(1) position of the second reactive site was identified only from genomic DNA. A phylogenetic tree constructed using grass pea BBIs with their homologs from other legume species revealed grouping based on taxonomy and on specificity of the reactive sites. Five BBI sequences, representing five different second reactive sites, were heterologously expressed in the yeast Pichia pastoris. The recombinant proteins demonstrated to be active against trypsin, while three of them were also active against chymotrypsin, and one against human leukocyte elastase. Comparative modeling and protein docking were used to further investigate interactions between two grass pea BBI isoforms and their target proteases. Thus two reliable 3D models have been proposed, representing two potential ternary complexes, each constituted of an inhibitor and its target enzymes. PMID- 22677448 TI - Increasing phosphatidylinositol (4,5) bisphosphate biosynthesis affects plant nuclear lipids and nuclear functions. AB - In order to characterize the effects of increasing phosphatidylinositol(4,5)bisphosphate (PtdIns(4,5)P(2)) on nuclear function, we expressed the human phosphatidylinositol (4)-phosphate 5-kinase (HsPIP5K) 1alpha in Nicotiana tabacum (NT) cells. The HsPIP5K-expressing (HK) cells had altered nuclear lipids and nuclear functions. HK cell nuclei had 2-fold increased PIP5K activity and increased steady state PtdIns(4,5)P(2). HK nuclear lipid classes showed significant changes compared to NT (wild type) nuclear lipid classes including increased phosphatidylserine (PtdSer) and phosphatidylcholine (PtdCho) and decreased lysolipids. Lipids isolated from protoplast plasma membranes (PM) were also analyzed and compared with nuclear lipids. The lipid profiles revealed similarities and differences in the plasma membrane and nuclei from the NT and transgenic HK cell lines. A notable characteristic of nuclear lipids from both cell types is that PtdIns accounts for a higher mol% of total lipids compared to that of the protoplast PM lipids. The lipid molecular species composition of each lipid class was also analyzed for nuclei and protoplast PM samples. To determine whether expression of HsPIP5K1alpha affected plant nuclear functions, we compared DNA replication, histone 3 lysine 9 acetylation (H3K9ac) and phosphorylation of the retinoblastoma protein (pRb) in NT and HK cells. The HK cells had a measurable decrease in DNA replication, histone H3K9 acetylation and pRB phosphorylation. PMID- 22677450 TI - A three-step culture system to increase the xanthone production and antifungal activity of Hypericum perforatum subsp. angustifolium in vitro roots. AB - Hypericum perforatum is a well-known medicinal plant. Among all secondary metabolites produced by this species, xanthones are very interesting for their antifungal activity. In the present study, with the aim to improve xanthone production and antifungal activity of H. perforatum subsp. angustifolium (sin. Frohlich) Borkh in vitro roots, a new methodology consisting of a three-step culture system, has been developed. Regenerated roots of H. perforatum were cultured in a three-step culture system: in the first step, to increase biomass, the roots were cultured in half-strength liquid Murashige and Skoog (MS) medium supplemented with 1 mg L(-1) indole butyric acid (IBA) and 1.5% sucrose. In the second and third steps, to stimulate secondary metabolism, the roots were cultured with 1.1 mg L(-1) 2,4-dichlorophenoxyacetic acid (2,4-D), 0.215 mg L(-1) kinetin (KIN), and 0.186 mg L(-1) 1-naphthalenacetic acid (NAA). In the third step, some of the roots were treated with chitosan. Xanthone production increased 2.7 times following the three-step method. The mean minimal inhibitory concentration (MIC) values were of 36.9, 26.7, and 65 MUg mL(-1), against Candida species, Cryptococcus neoformans and dermatophytes, respectively. A positive correlation between xanthone accumulation and antifungal activity has been shown. PMID- 22677451 TI - Tissue and method specificities of phenylalanine ammonia-lyase assay. AB - A large number of studies have estimated phenylalanine ammonia-lyase (PAL) activity because it strongly reacts to various stimuli. Activity of this enzyme has been assayed mainly by means of spectrophotometry, but the precision of this method is poorly known. We compared assays of PAL activity using spectrophotometry and high performance liquid chromatography (HPLC) in two species (Matricaria chamomilla and Arabidopsis thaliana). Additionally, copper exposed M. chamomilla plants and buffer with additive were also tested. Our data indicate that spectrophotometry both overestimates (leaves of M. chamomilla) and underestimates (leaves and roots of A. thaliana) PAL activity in comparison with HPLC, suggesting interference of UV-absorbing metabolites. HPLC also showed more accurate detection of cinnamic acid in Cu-exposed chamomile roots. Addition of dithiothreitol to the extraction buffer enhanced PAL activity but reduced proteins, indicating an artificial negative effect. A comparison of PAL activity in selected species is also provided. PMID- 22677452 TI - Metabolic engineering of D-xylose pathway in Clostridium beijerinckii to optimize solvent production from xylose mother liquid. AB - Clostridium beijerinckii is an attractive butanol-producing microbe for its advantage in co-fermenting hexose and pentose sugars. However, this Clostridium strain exhibits undesired efficiency in utilizing D-xylose, one of the major building blocks contained in lignocellulosic materials. Here, we reported a useful metabolic engineering strategy to improve D-xylose consumption by C. beijerinckii. Gene cbei2385, encoding a putative D-xylose repressor XylR, was first disrupted in the C. beijerinckii NCIMB 8052, resulting in a significant increase in D-xylose consumption. A D-xylose proton-symporter (encoded by gene cbei0109) was identified and then overexpressed to further optimize D-xylose utilization, yielding an engineered strain 8052xylR-xylT(ptb) (xylR inactivation plus xylT overexpression driven by ptb promoter). We investigated the strain 8052xylR-xylT(ptb) in fermenting xylose mother liquid, an abundant by-product from industrial-scale xylose preparation from corncob and rich in D-xylose, finally achieving a 35% higher Acetone, Butanol and Ethanol (ABE) solvent titer (16.91 g/L) and a 38% higher yield (0.29 g/g) over those of the wild-type strain. The strategy used in this study enables C. beijerinckii more suitable for butanol production from lignocellulosic materials. PMID- 22677453 TI - Role of allostatic load in sociodemographic patterns of pain prevalence in the U.S. population. AB - Persistent stressors associated with sociodemographic disadvantage exert a physiologic toll, labeled "allostatic load," that contributes to disparities in some health conditions. We investigated the contribution of allostatic load to pain prevalence in U.S. adults. Interviews with 14,184 adults in the 1999-2004 National Health and Nutrition Examination Survey asked about severe headache, pain that lasted >24 hours, and widespread pain. Ten biomarkers of allostatic load were quantified from blood (glycated hemoglobin), serum (C-reactive protein, homocysteine, cholesterol, triglycerides), urine (creatinine, albumin), and physical measurements (body mass index, systolic and diastolic blood pressure). Log-binomial regression models estimated prevalence ratios (PRs) and 95% confidence intervals (95% CIs). Prevalence ranged from 3.4% for widespread pain to 26.9% for pain >24 hours. After adjustment for demographic characteristics, low income was associated with greater prevalence of pain >24 hours (PR = 1.65, 95% CI = 1.49, 1.83), severe headache (PR = 2.05, 95% CI = 1.68, 2.50), and widespread pain (PR = 3.67, 95% CI = 2.56, 5.27). Racial/ethnic minorities had lower prevalence of all 3 pain conditions than non-Hispanic whites. While greater allostatic load was associated with elevated prevalence of pain, allostatic load did not meaningfully attenuate PRs associated with income or race/ethnicity. We conclude that greater pain prevalence among low-income groups is not explained by greater allostatic load. PERSPECTIVE: In U.S. adults, pain occurs more frequently in lower-income groups, although the relationship is not attributable to their experience of greater allostatic load. While allostatic load contributes to population variation in pain, other etiologic mechanisms contributing to pain are needed to account for income disparities in pain. PMID- 22677454 TI - Ultrasonic preparation of cationic cotton and its application in ultrasonic natural dyeing. AB - Cationization of cotton fabric was conferred by the sonicator reaction of cellulose with bromoacetyl bromide, followed by substitution of the terminal bromo groups by triethylamine. Experiments showed that the optimal volume of bromoacetyl bromide necessary to succeed the first stage was 0.4 mL. The order of weight gain for various processes indicates, ultrasound, 25 kHz> ultrasound, 40 kHz> mechanical stirring. Also, for the second stage the order of nitrogen contents indicates ultrasound, 25 kHz> ultrasound, 40 kHz> mechanical stirring. The structures of both untreated and cationic fibres were investigated by FTIR spectroscopy. Modified cotton fabric was subsequently dyed in both conventional and ultrasonic techniques with isosalipurposide dye isolated from Acacia cyanophylla yellow flowers. The effect of dye bath pH, ultrasonic power and frequency, dyeing time and temperature were studied and the order of K/S values indicates ultrasound, 25 kHz > ultrasound, 40 kHz > CH. ultrasound was also found to enhance the dye uptake and the overall fastness properties. Analysis of the sorption isotherms of isosalipurposide dye on cationic cotton fabric shows that the Languimir isotherm equation is best able to correlate the data. PMID- 22677455 TI - The impact of left ventricular lead position on left ventricular reverse remodelling and improvement in mechanical dyssynchrony in cardiac resynchronization therapy. AB - AIMS: To investigate the influence of left ventricular (LV) lead position on LV dyssynchrony in cardiac resynchronization therapy (CRT). METHODS AND RESULTS: The LV lead was prospectively targeted to the latest activated LV segment (concordant) evaluated by two-dimensional speckle tracking radial strain (ST-RS) echocardiography in 103 CRT recipients (67 +/- 12 years). Mechanical dyssynchrony was assessed by anteroseptal-to-posterior (AS-P) delay and interventricular mechanical delay (IVMD). Concordant LV leads were obtained in 72 (70%) patients. Superior LV reverse remodelling (LV-RR; >= 15% LV end-systolic volume reduction at 6-month follow-up) was observed in the concordant LV leads compared with the discordant LV leads [51 (76%) vs. 13 (45%); P = 0.003]. Mechanical resynchronization responders (>= 50% AS-P delay reduction at 6-month follow-up) obtained in the concordant LV leads [44 (66%)] was greater than in the discordant LV leads [10 (34%); P = 0.005]. The discordant LV leads located adjacent to the concordant LV leads (+1 segment; n = 22) and 2 segments apart (+2 segments; n = 9) were evaluated in a subgroup analysis. Mechanical resynchronization responders 6 months after CRT were as follows: in +1 segment [n = 10 (48%)] and in +2 segments (n = 0; P = 0.001). The concordant LV lead was the only independent predictor of LV-RR at 6-month follow-up (odds ratio, 4.177; P = 0.004). Independent predictors of mechanical resynchronization responders were AS-P delay (odds ratio, 1.007; P = 0.032), IVMD (odds ratio, 1.024; P = 0.038), and concordant LV lead (odds ratio, 4.691; P = 0.004). CONCLUSION: Concordant LV leads in CRT provided more responders according to both LV reverse remodelling and mechanical resynchronization. PMID- 22677456 TI - In vitro characterization of organophosphorus compound hydrolysis by native and recombinant human prolidase. AB - Human prolidase is a binuclear metalloenzyme, which can potentially function as a catalytic bioscavenger for organophosphorus (OP) nerve agents. Although the biochemical properties of native prolidase purified from human erythrocytes, liver, kidney, and fibroblast cells are well known, it is very poorly characterized with regard to its OP hydrolyzing activity. Also, the high cost of purification of large quantities of native enzyme limits its use as a bioscavenger. Thus, recombinant human prolidase with similar biochemical properties to those of native enzyme would be more suitable as a catalytic bioscavenger. In this study, we established an Escherichia coli expression system, which produced a large amount of tagged human liver prolidase that was purified to over 95% purity from the soluble fraction of cell lysate by affinity chromatography on Streptavidin-agarose resin. The catalytic properties of the recombinant enzyme were compared in vitro with those of highly purified prolidase I isolated from human erythrocytes. The catalytic properties of recombinant prolidase overlap with those of the erythrocyte-derived native enzyme. Both enzymes efficiently hydrolyzed diisopropylfluorophosphate, sarin, soman, tabun and cyclosarin, but were much less efficient at hydrolyzing paraoxon and methyl paraoxon. These results suggest that human prolidase expressed in E. coli is suitable for further development as a catalytic bioscavenger for OP nerve agents. PMID- 22677457 TI - Non-response bias in a community survey of drinking, alcohol-related experiences and public opinion on alcohol policy. AB - BACKGROUND: The continuing decline in response rates to household surveys is a concern for the health and social sciences as it increases the risk of selective non-response biasing the estimates of interest. METHODS: We analysed non-response bias in a postal survey measuring drinking behaviour, experience of harm and opinion on local government alcohol policies among residents in six New Zealand communities. The Continuum of Resistance model, which suggests that late respondents to a survey are most similar to non-respondents on the measures of interest, was used to guide our investigation. RESULTS: Men, younger people, those of Maori descent and those living in more deprived areas were less likely to respond to our survey than women, older people, those not of Maori descent and those living in comparatively affluent areas. Late respondents more closely resembled non-respondents demographically than early respondents. The prevalence of binge drinking and experience of assault was higher, and support for restrictive local government alcohol policies lower, among late respondents. Assuming the drinking behaviour and alcohol-related experiences of non respondents were the same as those of late respondents, prevalence was under estimated by 3.4% (relative difference: 13%) and 2.1% (relative difference: 21%) for monthly binge drinking and assault respectively. Policy support was not over estimated. CONCLUSION: The findings add to a growing body of evidence suggesting that surveys under-estimate risk behaviour because of selective non-response and this bias increases as response rates fall. Notably, public opinion may not be subject to such misestimation. PMID- 22677458 TI - Does active referral by a doctor or 12-Step peer improve 12-Step meeting attendance? Results from a pilot randomised control trial. AB - BACKGROUND: Active engagement in 12-Step self-help groups (SHG) is associated with improvements in substance use outcomes during and after treatment, yet levels of participation in SHG meetings in the U.K. remain low. METHOD: An RCT investigating the impact of active referral to SHG, delivered by doctors or 12 Step peers during inpatient treatment on both inpatient and post-treatment meeting attendance was conducted. 151 inpatients with alcohol, opiate, crack cocaine or benzodiazepine dependence undergoing detoxification, received one of two active referral interventions: 12-Step peer intervention (PI), doctor intervention (DI), or no intervention (NI). 83% of the sample was followed up, 2 3 months following discharge. RESULTS: Active referral interventions significantly increased attendance at 12-Step meetings during inpatient treatment (88% versus 73%, p<.05). Rates of post-discharge meeting attendance were PI=64%, DI=48%, NI=33%, with those in the PI group significantly (OR=3.6; CI=1.3, 9.8) more likely to have attended. Inpatient meeting attenders were three times as likely to have attended meetings post-discharge (59% versus 20%, p<.01), and post discharge meeting attenders reported significantly higher abstinence rates (60.8% versus 39.2%, p<.05) at follow-up. However, abstinence rates did not differ significantly across intervention groups (44% [PI], 41% [DI] and 36% [NI]). CONCLUSION: Attendance at 12-Step SHGs is associated with greater rates of abstinence and active referral, especially by 12-Step peers, increases 12-Step SHG attendance rates. However, improved clinical outcomes among attendees might not occur until stronger recovery peer support networks are established. These results show promise for the benefit of incorporating Twelve Step Facilitation into U.K. treatment settings. PMID- 22677460 TI - SOS induction and mutagenesis by dnaQ missense alleles in wild type cells. AB - Mistranslation leads to elevated mutagenesis and replication arrest, both of which are hypothesized to result from the presence of mixed populations of wild type and mistranslated versions of DNA polymerase III subunit proteins. Consistent with this possibility, expression of missense alleles of dnaQ (which codes for the proofreading subunit E) in wild type (dnaQ+) cells is shown to lead to SOS induction as well as mutagenesis. Exposure to sublethal concentrations of streptomycin, an aminoglycoside antibiotic known to promote mistranslation, also leads to SOS induction. PMID- 22677459 TI - Cross-cultural differences in cognitive development: attention to relations and objects. AB - Growing evidence indicates a suite of generalized differences in the attentional and cognitive processing of adults from Eastern and Western cultures. Cognition in Eastern adults is often more relational and in Western adults is more object focused. Three experiments examined whether these differences characterize the cognition of preschool children in the two cultures. In Experiment 1, 4-year-olds from the two cultures (N=64) participated in a relational match-to-standard task in two conditions, with simple or richly detailed objects, in which a focus on individual objects may hurt performance. Rich objects, consistent with past research, strongly limited the performance of U.S. children but not Japanese children. In Experiment 2, U.S. and Japanese 4-year-olds (N=72) participated in a visual search task that required them to find a specific object in a cluttered, but organized as a scene, visual field in which object-centric attention might be expected to aid performance and relational attentional pattern may hinder the performance because of relational structure that was poised by the scene. U.S. children outperformed Japanese children. In Experiment 3, 4-year-olds from both cultures (N=36) participated in a visual search task that was similar to Experiment 2 but with randomly placed objects, where there should not be a difference between the performance of two cultures because the relational structure that may be posed by the scene is eliminated. This double-dissociation is discussed in terms of implications for different developmental trajectories, with different developmental subtasks in the two cultures. PMID- 22677461 TI - Roles of cADPR and NAADP in pancreatic cells. AB - Cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP) are Ca(2+)-mobilizing nucleotides that were discovered in the late 1980s. Two decades of investigations have built up a considerable understanding about these two molecules that are related because both are derived from pyridine nucleotides and known to be generated by CD38/ADP-ribosyl cyclases. cADPR has been shown to target the ryanodine receptors in the endoplasmic reticulum whereas NAADP stimulates the two-pore channels in the endo-lysosomes. Accumulating results indicate that cADPR and NAADP are second messenger molecules mediating Ca(2+) signaling activated by a wide range of agonists. This article reviews what is known about these two molecules, especially regarding their signaling roles in the pancreatic cells. PMID- 22677462 TI - [Optical coherence tomography in neuro-ophthalmology]. AB - INTRODUCTION: Optical coherence tomography (OCT) is a potential tool for diagnosis and follow-up in diseases of the anterior visual pathway in that it provides a reproducible and reliable quantification of retinal nerve fiber layer (RNFL) thickness. A review of the literature was conducted to define the utility of OCT in neuro-ophthalmology. MATERIALS AND METHODS: The clinical applications of RNFL thickness measurement by OCT time domain were analyzed. The PubMed search engine enabled us to select the relevant publications, using the following keywords: "optic neuropathy", "retinal nerve fiber layer thickness", and "optical coherence tomography". Publications concerning glaucoma were excluded from this review. RESULTS: The course of RNFL thickness depends on the underlying disease: (I) progressive reduction toward atrophy (e.g., optic neuritis, chiasmal compression) or (II) initial increase in RNFL thickness followed by a reduction toward (IIa) normalization (papilledema) or (IIb) atrophy (anterior ischemic optic neuropathy, Leber hereditary optic neuropathy). DISCUSSION: Depending on the type of anterior visual pathway impairment, OCT provides RNFL data relevant for diagnosis, follow-up, and prognosis. As in macular disease, OCT has become an important clinical tool for routine disease assessment in neuro-ophthalmology. PMID- 22677463 TI - Successful cricoid fracture reduction using a balloon dilator. AB - The traditional treatment of cricoid cartilage fractures concurrent with subglottic stenosis in pediatric patients usually requires an open approach with a high rate of complications and morbidity. We present here a case report of a successful treatment of a cricoid cartilage fracture concurrent with a subglottic stenosis in an adolescent patient using balloon dilation. The mentioned procedure reduced the fracture and allowed us to prevent a tracheostomy and its complications. PMID- 22677464 TI - Endonasal endoscopic approach for intracranial nasal dermoid sinus cysts in children. AB - Nasal dermoid sinus cysts are the most common congenital midline nasal lesions. The frequency of intracranial extensions varies from 5% to 45%. Complete surgical excision of nasal dermoid cyst and any associated sinus tract is essential for cure and any residual ectodermal elements result in a high rate of recurrence and complicated infections. Many different approaches have been described for the removal of nasal dermoids in the past two decades, ranging from a simple extracranial excision to complex procedures in which a combined extracranial intracranial approach is required. We hereby report two cases of nasal dermoid sinus cysts in children with intracranial extension which were managed with an endonasal endoscopic procedure. We describe the technique we implemented for this procedure and for the reconstruction of the skull base defect. PMID- 22677465 TI - Antimicrobial resistance to benzylpenicillin in invasive pneumococcal disease in Belgium, 2003-2010: the effect of altering clinical breakpoints. AB - The Belgian data (2003-2010) for the European Antimicrobial Resistance Surveillance Network (EARS-Net) showed a significant decreasing trend in the proportion of penicillin non-susceptible Streptococcus pneumoniae (9.4% to <1%) from blood and CSF isolates. We found that 75% of this decrease was explained by a change in Clinical and Laboratory Standards Institute (CLSI) breakpoints as the trend disappeared if only the new breakpoints were applied. Applying only European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints also resulted in a relatively stable proportion of penicillin non-susceptibility (average 5%), but this proportion was 7-13 times higher than with the new CLSI breakpoints. When the new CLSI breakpoints alone are used, fewer than 1% of bacteraemia isolates were penicillin non-susceptible during the entire period, but the proportion of non-susceptible meningitis isolates rose from 6.3% in 2003 to 15.9% between 2003 and 2010. Changing breakpoints should lead to retrospective analysis of historical data to minimize wrongly interpreting resistance trends. PMID- 22677466 TI - [Fungus patents: from Pasteur to the present day]. AB - At the end of the 19(th) century, the American Patent Office granted the patent known as "Pasteur's application", claiming the protection of a yeast strain. Since that date, the debate around biotechnology patents, especially for those that affect living organisms or part of them, has grown exponentially. In the present article, the Patent Law is reviewed, pointing out the particular problems about fungi or parts of them. Also, some of the fungus patents are discussed from the perspective of the ethical, economical, social and environmental aspects of these kind of patents. PMID- 22677468 TI - Identification of possible risk factors for the development of dopamine agonist withdrawal syndrome in Parkinson's disease. PMID- 22677467 TI - Patients with peripheral arterial disease exhibit reduced joint powers compared to velocity-matched controls. AB - Previous studies have shown major deficits in gait for individuals with peripheral arterial disease before and after the onset of pain. However, these studies did not have subjects ambulate at similar velocities and potential exists that the differences in joint powers may have been due to differences in walking velocity. The purpose of this study was to examine the joint moments and powers of peripheral arterial disease limbs for subjects walking at similar self selected walking velocities as healthy controls prior to onset of any symptoms. Results revealed peripheral arterial disease patients have reduced peak hip power absorption in midstance (p=0.017), reduced peak knee power absorption in early and late stance (p=0.037 and p=0.020 respectively), and reduced peak ankle power generation in late stance (p=0.021). This study reveals that the gait of patients with peripheral arterial disease walking prior to the onset of any leg symptoms is characterized by failure of specific and identifiable muscle groups needed to perform normal walking and that these gait deficits are independent of reduced gait velocity. PMID- 22677469 TI - Modeling and prediction of density distribution and microstructure in particleboards from acoustic properties by correlation of non-contact high resolution pulsed air-coupled ultrasound and X-ray images. AB - Non-destructive density and microstructure quality control testing in particleboards (PBs) is necessary in production lines. A pulsed air-coupled ultrasound (ACU) high-resolution normal transmission system, together with a first wave tracking algorithm, were developed to image amplitude transmission G(p) and velocity c(p) distributions at 120kHz for PBs of specific nominal densities and five particle geometries, which were then correlated to X-ray in plane density images rho(s). Test PBs with a homogeneous vertical density profile were manufactured in a laboratory environment and conditioned in a standard climate (T=20 degrees C, RH=65%) before the measurements. Continuous trends (R(2)>0.97) were obtained by matching the lateral resolution of X-ray images with the ACU sound field radius (sigma(w)(o)=21mm) and by clustering the scatter plots. rho(s)?c(p) was described with a three-parameter non-linear model for each particle geometry, allowing for ACU density prediction with 3% uncertainty and PB testing according to EN312. rho(s)?G(p) was modeled by calculating ACU coupling gain and by fitting inverse power laws with offset of rho(s) and c(p) to material attenuation, which scaled with particle volume. G(p) and c(p) variations with the frequency were examined, showing thickness resonances and scattering attenuation. The combination of ACU and X-ray data enabled successful particle geometry classification. The observed trends were interpreted in terms of multi-scale porosity and grain scattering with finite-difference time-domain simulations, which modeled arbitrarily complex stiffness and density distributions. The proposed method allows for non-contact determination of relations between acoustic properties and in-plane density distribution in plate materials. In future work, commercial PBs with non-uniform vertical density profiles should be investigated. PMID- 22677470 TI - The pharmacological profile of ELIC, a prokaryotic GABA-gated receptor. AB - The Erwinia ligand-gated ion channel (ELIC) is a bacterial homologue of vertebrate Cys-loop ligand-gated ion channels. It is activated by GABA, and this property, combined with its structural similarity to GABA(A) and other Cys-loop receptors, makes it potentially an excellent model to probe their structure and function. Here we characterise the pharmacological profile of ELIC, examining the effects of compounds that could activate or inhibit the receptor. We confirm that a range of amino acids and classic GABA(A) receptor agonists do not elicit responses in ELIC, and we show the receptor can be at least partially activated by 5-aminovaleric acid and gamma-hydroxybutyric acid, which are weak agonists. A range of GABA(A) receptor non-competitive antagonists inhibit GABA-elicited ELIC responses including alpha-endosulfan (IC50 = 17 MUM), dieldrin (IC50 = 66 MUM), and picrotoxinin (IC50 = 96 MUM) which were the most potent. Docking suggested possible interactions at the 2' and 6' pore-lining residues, and mutagenesis of these residues supports this hypothesis for alpha-endosulfan. A selection of compounds that act at Cys-loop and other receptors also showed some efficacy at blocking ELIC responses, but most were of low potency (IC50 > 100 MUM). Overall our data show that a number of compounds can inhibit ELIC, but it has limited pharmacological similarity to GLIC and to Cys-loop receptors. PMID- 22677473 TI - The effect of triclosan on hormone secretion and viability of human choriocarcinoma JEG-3 cells. AB - Triclosan is an antimicrobial agent frequently used in pharmaceuticals and personal care products. We analyzed triclosan for its action on placental secretion of progesterone, estradiol and human chorionic gonadotropin in vitro in the JEG-3 cells. We also investigated its action on cell viability, proliferation and apoptosis. The JEG-3 cells were cultured with increasing doses of triclosan (1*10(-9)-1*10(-4) M) for 24, 48 and 72 h. Triclosan was found to increase estradiol and progesterone secretion after short- and long-term exposure. The stimulatory effect was observed up to 10 MUM after short- and long-term exposure to triclosan. In addition, triclosan caused an adverse effect on beta-hCG secretion. The highest doses of triclosan (50 and 100 MUM) showed a strong cytotoxic effect. Anti proliferative and pro-apoptotic effects were also observed. Overall, this study demonstrates that triclosan may indirectly disrupt steroidogenesis which may, in turn, affect placental development and consequently fetal growth. PMID- 22677471 TI - Downregulation of brain phosphodiesterase type IV measured with 11C-(R)-rolipram positron emission tomography in major depressive disorder. AB - BACKGROUND: Phosphodiesterase type IV (PDE4), an important component of the cyclic adenosine monophosphate (cAMP) cascade, selectively metabolizes cAMP in the brain to the inactive monophosphate. Basic studies suggest that PDE4 mediates the effects of several antidepressants. This study sought to quantify the binding of 11C-(R)-rolipram, a PDE4 inhibitor, as an indirect measure of this enzyme's activity in the brain of individuals with major depressive disorder (MDD) compared with healthy control subjects. METHODS: 11C-(R)-Rolipram brain positron emission tomography scans were performed in 28 unmedicated MDD subjects and 25 age- and gender-matched healthy control subjects. Patients were moderately depressed and about one half were treatment-naive. 11C-(R)-Rolipram binding in the brain was measured using arterial 11C-(R)-rolipram levels to correct for the influence of cerebral blood flow. RESULTS: Major depressive disorder subjects showed a widespread, approximately 20% reduction in 11C-(R)-rolipram binding (p = .002), which was not caused by different volumes of gray matter. Decreased rolipram binding of similar magnitudes was observed in most brain areas. Rolipram binding did not correlate with the severity of depressive or anxiety symptoms. CONCLUSIONS: This study is the first to demonstrate that brain levels of PDE4, a critical enzyme that regulates cAMP, are decreased in unmedicated individuals with MDD in vivo. These results are in line with human postmortem and rodent studies demonstrating downregulation of the cAMP cascade in MDD and support the hypothesis that agents such as PDE4 inhibitors, which increase activity within the cAMP cascade, may have antidepressant effects. PMID- 22677472 TI - Persistent developmental toxicity in rat offspring after low dose exposure to a mixture of endocrine disrupting pesticides. AB - There is growing concern of permanent damage to the endocrine and nervous systems after developmental exposure to endocrine disrupting chemicals. In this study the permanent reproductive and neurobehavioral effects of combined exposure to five endocrine disrupting pesticides, epoxiconazole, mancozeb, prochloraz, tebuconazole and procymidone, were examined. Pregnant and lactating rat dams were dosed with a mixture of the five pesticides at three different doses, or with the individual pesticides at one of two doses. Adverse effects were observed in young and adult male offspring from the group exposed to the highest dose of the mixture. These included reduced prostate and epididymis weights, increased testes weights, altered prostate histopathology, increased density of mammary glands, reduced sperm counts, and decreased spatial learning. As no significant effects were seen following single compound exposure at the doses included in the highest mixture dose, these results indicate cumulative adverse effects of the pesticide mixture. PMID- 22677474 TI - Feasibility of the extended one-generation reproductive toxicity study (OECD 443). AB - The extended one-generation reproduction toxicity study (OECD 443, adopted 28 July-2011) produces more information with fewer animals than the two-generation study (OECD 416), by including F1 neurotoxicity and immunotoxicity assessments, and omitting an F2 generation if there are no relevant F1 findings. This saves >1000 animals per compound. Feasibility studies based on draft OECD443 were conducted in industrial GLP laboratories in Europe and USA, using vinclozolin, methimazole and lead acetate. A fourth study was conducted with 2,4 dichlorophenoxyacetic acid (2,4-D) in response to a regulatory request for reproduction and developmental neurotoxicity data. The studies effectively profiled vinclozolin as an anti-androgenic developmental toxicant, methimazole as a developmental anti-thyroid agent, and lead acetate as a systemic and developmental toxicant. The 2,4-D study demonstrated the value of toxicokinetic data in dose setting and data interpretation. These results illustrate the variety of reproductive and developmental endpoints which can be captured in this complex but manageable study design. Time constraints for triggering further (F2) testing are summarized. PMID- 22677475 TI - Effect of tetrabrombisphenol A on induction of apoptosis in the testes and changes in expression of selected testicular genes in CD1 mice. AB - Tetrabromobisphenol A (TBBPA) is a substance widely used in industry as a flame retardant. TBBPA was found in the environment and was detected even in the human body. The effect of this chemical was observed in different cell lines in vitro and it is supposed that TBBPA may affect various hormonal systems in vivo. In this study we examined the effect of TBBPA on the reproductive parameters of two generations of outbred mice in vivo. Experimental and control animals of F1 generation were bred in various conditions to enable evaluation of the possible trans-generational effect. An increased incidence of apoptosis in the testes and changes in the morphometry of seminiferous tubules was detected in the experimental animals. In addition, changes in the expression pattern of selected genes encoding proteins that play an important role during spermatogenesis were observed. In contrast, sperm quality and reproduction were not affected by TBBPA. PMID- 22677476 TI - [Mourning a chronic disease: diagnostic error experienced by two families]. AB - We report on two pediatric cases with a diagnosis of hereditary metabolic disease established for several years and secondarily disproved. Retrospective interviews conducted 1 year after the announcement of the absence of the illness, the psychological reactions were analyzed. Through this clinical experience, the authors suggest that the traumatism caused by the announcement of the diagnosis may be similar to that which occurred when invalidation of the disease is pronounced. Four steps predominate: relief, anger, guilt, and problems mourning the disease experienced in solitude. PMID- 22677477 TI - [How to overcome the refusal to identify child abuse?]. PMID- 22677478 TI - [Drugs news]. PMID- 22677479 TI - PCR detection and PFGE genotype analyses of streptococcal clinical isolates from tilapia in China. AB - Large-scale streptococcal outbreaks occurred continuously in tilapia farms of China from 2009 to 2011. The objective of this study was to characterize the prevalent strains of tilapia streptococci from the main cultured areas of China through species specific PCR and pulse field gel electrophoresis (PFGE). A total of 105 prevalent strains were isolated from Guangdong, Guangxi, Hainan and Fujian provinces between 2006 and 2011, 85 of which were identified as Streptococcus agalactiae while the rest were all identified as Streptococcus iniae. The prevalent stains in 2006 and 2007 were S. iniae (94.7%, 18/19), with S. agalactiae account for only 5.3% (1/19); The prevalent strains in 2009 and 2011 however changed to S. agalactiae (97.7%, 84/86), with only 2.3% (2/86) was S. iniae. Of these 105 strains, a total of 13 PFGE types (A-M) were characterized, among which D, F, G and K genotypes were predominant, accounting for 81.90% (86/105). The cluster analysis of PFGE electropherograms separated S. iniae and S. agalactiae to two distinctive branches, 20 strains of S. iniae exhibiting 3 types of PFGE band patterns with a similarity of 94.8-100%, and the 85 strains of S. agalactiae producing 10 types of PFGE band patterns with a similarity between 48.4% and 100%. Data suggested that the prevalent strains of tilapia streptococci in China have shifted from the former (before 2008) dominant strains of S. iniae to the current (2009-2011) dominant strains of S. agalactiae. Moreover, PFGE genotypes of the prevalent strains demonstrated geographic differences and temporal changes. PMID- 22677480 TI - The intramammary efficacy of first generation cephalosporins against Staphylococcus aureus mastitis in mice. AB - Staphylococcus aureus-induced mastitis in cattle causes important financial losses in the dairy industry due to lower yield and bad milk quality. Although S. aureus is susceptible to many antimicrobials in vitro, treatment often fails to cure the infected udder. Hence, comprehensive evaluation of antimicrobials against S. aureus mastitis is desirable to direct treatment strategies. The mouse mastitis model is an elegant tool to evaluate antimicrobials in vivo while circumventing the high costs associated with bovine experiments. An evaluation of the antimicrobial efficacy of the intramammary (imam) applied first generation cephalosporins cefalexin, cefalonium, cefapirin and cefazolin, was performed using the S. aureus mouse mastitis model. In vivo determination of the effective dose 2log(10) (ED(2log10)), ED(4log10), protective dose 50 (PD(50)) and PD(100) in mouse mastitis studies, support that in vitro MIC data of the cephalosporins did not fully concur with the in vivo clinical outcome. Cefazolin was shown to be the most efficacious first generation cephalosporin to treat S. aureus mastitis whereas the MIC data indicate that cefalonium and cefapirin were more active in vitro. Changing the excipient for imam application from mineral oil to miglyol 812 further improved the antimicrobial efficacy of cefazolin, confirming that the excipient can influence the in vivo efficacy. Additionally, statistical analysis of the variation of S. aureus-infected, excipient-treated mice from fourteen studies emphasizes the strength of the mouse mastitis model as a fast, cost effective and highly reproducible screening tool to assess the efficacy of antimicrobial compounds against intramammary S. aureus infection. PMID- 22677481 TI - Improved identification including MALDI-TOF mass spectrometry analysis of group D streptococci from bovine mastitis and subsequent molecular characterization of corresponding Enterococcus faecalis and Enterococcus faecium isolates. AB - We examined 199 group D streptococci isolated from clinically defined and epidemiologically unrelated cases of bovine mastitis. Samples were collected during a 5-month period from 2010 to 2011 from diseased animals in 199 herds (1 isolate per herd) raised in different counties and federal states in Germany. A classical enterococcal species identification procedure started with PYRase and catalase assays, growth on Enterococcoselagar((r)) and GCG((r)) agar plates and in 6.5% NaCl followed by a biochemical reaction panel. All 199 isolates were also subjected to MALDI-TOF MS diagnostics in which a simple and an extended direct transfer protocol were compared. The latter revealed a much better performance (higher log (score) values) although the same result was obtained in all but three cases. Classical and MALDI TOF MS analyses identified 64 Enterococcus faecalis and 37 Enterococcus faecium isolates which were confirmed by species specific PCRs. These 101 enterococcal isolates did not display a specific multi resistance phenotype and resistances to glycopeptides and antibiotics of last resort (linezolid, daptomycin, tigecycline) were absent, resistance to tetracycline was the most frequent resistance feature. Molecular typing of the 64 E. faecalis isolates revealed 3 main PFGE clusters of related strains represented by three MLST types (ST40, ST211, ST268). PFGE and MLST analysis of E. faecium isolates revealed several smaller clusters of only a few related strains and identified a number of previously unknown allele and MLST types (n=6; ST624 ST629) besides known variants (ST22, ST32). One of the 37 E. faecium strains showed properties of hospital-associated E. faecium strains (ampicillin resistance, IS16-positive; MLST CC17). PMID- 22677482 TI - Comparative minimum inhibitory and mutant prevention drug concentrations of enrofloxacin, ceftiofur, florfenicol, tilmicosin and tulathromycin against bovine clinical isolates of Mannheimia haemolytica. AB - Mannheimia haemolytica is the most prevalent cause of bovine respiratory disease (BRD) and this disease accounts for 75% of morbidity, 50-70% of feedlot deaths and is estimated to cost up to $1 billion dollars annually in the USA. Antimicrobial therapy is essential for reducing morbidity, mortality and impacting on the financial burden of this disease. Due to the concern of increasing antimicrobial resistance, investigation of antibacterial agents for their potential for selecting for resistance is of paramount importance. A novel in vitro measurement called the mutant prevention concentration (MPC) defines the antimicrobial drug concentration necessary to block the growth of the least susceptible cells present in high density (>=10(7) colony forming units/ml) bacterial populations such as those seen in acute infection. We compared the minimum inhibitory concentration (MIC) and MPC values for 5 antimicrobial agents (ceftiofur, enrofloxacin, florfenicol, tilmicosin, tulathromycin) against 285 M. haemolytica clinical isolates. The MIC(90)/MPC(90) values for each agent respectively were as follows: 0.016/2, 0.125/1, 2/>=16, 8/>=32, 2/8. Dosing to achieve MPC concentrations (where possible) may serve to reduce the selection of bacterial subpopulations with reduced antimicrobial susceptibility. The rank order of potency based on MIC(90) values was ceftiofur > enrofloxacin > florfenicol = tulathromycin > tilmicosin. The rank order of potency based on MPC(90) values was enrofloxacin > ceftiofur > tulathromycin > florfenicol >= tilmicosin. PMID- 22677483 TI - The challenge of developing a new predictive formula to estimate energy requirements in ventilated critically ill children. AB - BACKGROUND: Traditionally, energy requirements have been calculated using predictive equations. These methods have failed to calculate energy expenditure accurately. Routine indirect calorimetry has been suggested, but this method is technically demanding and costly. This study aimed to develop a new predictive equation to estimate energy requirements for critically ill children. METHODS: This prospective, observational study on ventilated children included patients with an endotracheal tube leak of < 10% and fractional inspired oxygen of < 60%. An indirect calorimetry energy expenditure measurement was performed and polynomial regression analysis was used to develop new predictive equations. The new formulas were then compared with existing prediction equations. RESULTS: Data from 369 measurements were included in the formula design. Only weight and diagnosis influenced energy expenditure significantly. Three formulas (A, B, C) with an R2 > 0.8 were developed. When we compared the new formulas with commonly used equations (Schofield, Food and Agriculture Organization/World Health Organization/United Nations University, and White equation), all formulas performed very similar, but the Schofield equation seemed to have the lowest SD. CONCLUSIONS: All 3 new pediatric intensive care unit equations have R2 values of > 0.8; however, the Schofield equation still performed better than other predictive methods in predicting energy expenditure in these patients. Still, none of the predictive equations, including the new equations, predicted energy expenditure within a clinically accepted range, and further research is required, particularly for patients outside the technical scope of indirect calorimetry. PMID- 22677484 TI - A contemporary view on endothelial function in heart failure. AB - The assessment of different aspects of endothelial dysfunction in cardiovascular medicine in general and in heart failure (HF) has been the focus of intense research, and includes vasomotor, haemostatic, antioxidant, and inflammatory activities. Differences also exist in the pattern of endothelial dysfunction depending on aetiology, severity, and stability of HF in individual patients. In the majority of patients with ischaemic aetiology of HF, endothelial dysfunction is systemic in its nature and involves both arteries and veins, conductance vessels and microvascular beds, coronary, pulmonary, and peripheral vessels. The pattern of endothelial dysfunction is more heterogeneous in non-ischaemic HF, with fewer features of systemic abnormalities. Indeed, many subjects with non ischaemic HF have a functionally preserved endothelium in peripheral arteries, with endothelial dysfunction seen only in coronary vessels. Endothelial dysfunction has significant prognostic value in HF, but its clinical application is hampered by methodological limitations in its assessment. Various medications (including angiotensin-converting enzyme inhibitors and statins) and regular physical activity have been shown to improve endothelial function in HF. However, there are still no pharmaceutical agents specifically targeting the vascular endothelium. Despite the large number of studies, the pathophysiological role of the vascular endothelium and its clinical potential as a therapeutic target has not yet been sufficiently developed and undoubtedly awaits further exploration. PMID- 22677485 TI - High-performance liquid chromatographic assay for ziprasidone in plasma samples: application to pharmacokinetic studies in rats. AB - Ziprasidone (ZRS) is among the various antipsychotic drugs indicated for treating schizophrenia. The determination of the pharmacokinetic behavior of this drug is of utmost importance in evaluating its bioavailability. The objectives of the present study are: (1) to develop and validate a sensitive, specific, accurate and precise reverse-phase high performance liquid chromatographic method for quantification of ZRS in the plasma of rats; and (2) to apply the developed method to study the pharmacokinetic profile of ZRS in rats after oral administration. The method uses a C18 (250.0 * 4.6 mm, 5 um) column and ultraviolet detector with wavelength set at 210.0 nm. The mobile phase is acetonitrile-phosphate buffer (pH 3.6) 28:72% v/v at a flow rate of 1.0 mL/min. The internal standard (IS) is escitalopram. The extraction procedure for ZRS and IS from the biological matrix (plasma) employs liquid-liquid extraction technique using a mixture of methyl tert-butyl ether-dichloromethane (70:30% v/v). The results show good accuracy and precision over a linearity range of 20.0-3,000.0 ng/mL with r(2) >= 0.9986. The mean recoveries of ZRS and IS are 79.32 +/- 1.16 and 84.10 +/- 3.2%, respectively. The method has been successfully utilized to study the pharmacokinetic profile of ZRS in rats after oral administration. PMID- 22677486 TI - 2D capillary electrophoresis hyphenated with spectral detection for the determination of quinine in human urine. AB - The possibilities of a column coupling two-dimensional capillary electrophoresis (2D CE) combined with fiber-based diode array detection (DAD) for the direct, highly reliable and ultrasensitive quantitative determination of quinine in real multicomponent ionic matrices (human urine) are demonstrated in this work. The capillary isotachophoresis (CITP) stage provided an on-line sample pretreatment (elimination of interfering matrix constituents, preseparation and preconcentration of the analyte) before the capillary zone electrophoresis (CZE) separation. Due to the large volume (30 uL) sample injection and CITP sample preconcentration, a simple absorbance photometric detection was sufficient for obtaining very low concentration limits of detection (~8.6 ng/mL). The combination of the different separation mechanisms (CITP and CZE) resulted in enhanced separation selectivity. This enabled us to obtain a pure analyte zone in the directly injected real samples suitable for qualitative and quantitative evaluation. The spectral DAD allowed (i) characterization of the purity (i.e., spectral homogeneity) of the analyte zone; and (ii) preliminary indication of structurally related compounds (i.e., potential biodegradation products of quinine), via characteristic spectra recorded in intervals of 200-800 nm. The CITP-CZE-DAD method was characterized by favorable performance parameters that are suitable for its routine biomedical use. One of the primary benefits of the CITP-CZE-DAD method is the possibility of performing direct injections of real biological samples while avoiding external sample preparation procedures and, therefore, enhancing the reliability and applicability of analyses and the potential for method automatization and miniaturization. PMID- 22677487 TI - Enantiomeric separation of verapamil and its active metabolite, norverapamil, and simultaneous quantification in human plasma by LC-ESI-MS-MS. AB - A simple, selective and high-throughput liquid chromatography-tandem mass spectrometry method has been developed and validated for the chromatographic separation and quantification of (R)- and (S)-enantiomers of verapamil and its active metabolite, norverapamil, in human plasma. All four analytes along with deuterated internal standards (D(6)-verapamil and D(6)-norverapamil) were extracted from 50 uL human plasma by liquid-liquid extraction. Separation was achieved on a Chiralcel OD-RH (150 * 4.6 mm, 5 um) analytical column with resolution factors of 1.4 and 1.9 for (R)- and (S)-enantiomers of verapamil and norverapamil, respectively. A mobile phase consisting of 0.05% trifluoroacetic acid in water-acetonitrile (70:30, v/v) afforded capacity factors of 2.45, 3.05, 2.27 and 3.13 for (R)- and (S)-enantiomers of verapamil and norverapamil, respectively. Detection was carried out on a triple quadrupole mass spectrometer, operating in the multiple reaction monitoring and positive ion modes. The method was validated over the concentration range of 1.0-250.0 ng/mL for all four analytes. Absolute recovery for the analytes ranged from 91.1 to 108.1%. Matrix factors calculated at three quality control levels varied from 0.96-1.07. The method was successfully applied to a pharmacokinetic study in 18 healthy Indian males after oral administration of a 240-mg verapamil tablet formulation under fasting conditions. PMID- 22677488 TI - Gradient HPLC-DAD determination of two pharmaceutical mixtures containing the antihistaminic drug ebastine. AB - This work describes the development, validation and application of a simple and reliable high-performance liquid chromatography-diode array detection (HPLC-DAD) procedure for the analysis of two pharmaceutical mixtures. The first mixture contains the antihistaminic drug ebastine (EBS) and the famous sympathomimetic drug pseudoephedrine hydrochloride (PSD), and the second mixture is composed of EBS and another sympathomimetic agent, phenylephrine hydrochloride (PHR). Effective chromatographic separation of EBS, PSD and PHR was achieved using a Zorbax SB-C8 (4.6 * 250 mm, 5 MUm) column with gradient elution of the mobile phase composed of 0.05M phosphoric acid and acetonitrile. The gradient elution started with 20% (by volume) acetonitrile, ramped up linearly to 90% in 5 min, then kept constant until the end of the run. The mobile phase was pumped at a flow rate of 1 mL/min. The multiple wavelength detector was set at 254 (for EBS and PSD) and 274 nm (for PHR) and quantification of the analytes was based on measuring their peak areas. The retention times for PHR, PSD and EBS were approximately 2.5, 2.9 and 7.1 min, respectively. The reliability and analytical performance of the proposed HPLC procedure were statistically validated with respect to linearity, ranges, precision, accuracy, selectivity, robustness and detection and quantification limits. Calibration curves were linear in the ranges 5-100, 100-1,000 and 10-200 ug/mL for EBS, PSD and PHR, respectively, with correlation coefficients > 0.9996. The validated HPLC method was applied to the analysis of the two pharmaceutical mixtures in laboratory-made tablets in which the analytes were successfully quantified with good recovery values and no interfering peaks were encountered from the inactive ingredients. Finally, the proposed method made use of DAD as a tool for peak identity and purity confirmation. PMID- 22677489 TI - Malignant fibrous histiocytoma: changing perceptions and management challenges. AB - Malignant fibrous histiocytoma (MFH) is a rare neoplasm exhibiting a propensity for aggressive clinical behavior. This review seeks to provide the practicing dermatologist with a contemporary understanding of MFH in order to guide management decisions. An extensive review of the literature was conducted using PubMed and OVID databases, searching for articles regarding MFH and undifferentiated pleomorphic sarcoma. The modern conception of MFH has changed extensively from clinical and pathologic standpoints. Limitations of the study included the reliability of past studies given the changing nature of MFH as a diagnostic entity. MFH represents an aggressive neoplasm with unique molecular, immunohistochemical, and behavioral characteristics. Practicing clinicians would benefit from a contemporary understanding of these tumors, particularly as a discussion of advances in the conception of MFH is largely absent in the dermatologic literature. PMID- 22677490 TI - The in vivo dynamic interplay of MDC1 and 53BP1 at DNA damage-induced nuclear foci. AB - MDC1 (NFBD1) and 53BP1 are critical mediators of the mammalian DNA damage response (DDR) at nuclear foci. Here we show by quantitative imaging assays that MDC1 and 53BP1 are similar in total copy number (~1200 copies per focus), but differ substantially in dynamics at both replication-associated nuclear bodies in normal cells and DNA repair foci in ionizing radiation (IR)-damaged cells. The majority of MDC1 (~80%) is extremely mobile and under continuous exchange, with only a small fraction (~20%) remaining immobile at foci irrespective of IR treatment. By contrast, 53BP1 has a smaller mobile fraction (~35%) and a larger immobile fraction (~65%) at nuclear bodies, and becomes more dynamic (~20% increase in mobile pool) upon IR-induced DNA damage. More specifically, the dynamics of 53BP1 is dependent on a minimal foci-targeting region (1231-1709), and differentially regulated by its N-terminus (1-1231) and C-terminal tBRCT domain (1709-1972). Furthermore, MDC1 knockdown, or disruption of 53BP1-MDC1 interaction, reduced the number of 53BP1 molecules at foci by ~60%, but only modestly affected 53BP1 retention. This novel in vivo evidence reveals distinct dynamics of MDC1 and 53BP1 at different types of nuclear structures, and shows that MDC1 directly recruits and retains a subset of 53BP1 for DNA repair. PMID- 22677491 TI - Arteriolar vascular smooth muscle cells: mechanotransducers in a complex environment. AB - Contraction of small artery (diameters typically less than 250 MUm) vascular smooth muscle cells (VSMCs) plays a critical role in local control of blood flow and arterial pressure through its affect on vascular caliber. Specifically, contraction of small arteries in response to increased intraluminal pressure is referred to as the myogenic response and represents an important role for mechanotransduction. Critical questions remain as to how changes in pressure are sensed by VSMCs and transduced across the cell membrane to tune the contractile state of the cell. Recent studies suggest a pivotal role for interactions between VSMCs and extracellular matrix (ECM) proteins. Thus, pressure-induced deformation of ECM proteins and their cell surface receptors (for example, integrins) may initiate contraction and cytoskeletal remodeling through modulation of ion channels, membrane depolarization, increased intracellular Ca(2+) and actomyosin crossbridge cycling. Importantly, it is argued that the contractile properties of small artery VSMCs reflect an intimate and integrated interaction with their extracellular environment and the three-dimensional structure of the vessel wall. PMID- 22677492 TI - Cerebrospinal fluid markers for Alzheimer's disease in a cognitively healthy cohort of young and old adults. AB - BACKGROUND: Low amyloid beta42 (Abeta42) and high total tau and phosphorylated tau (p-tau) concentrations in the cerebrospinal fluid (CSF) are biomarkers of Alzheimer's disease (AD), reflecting brain deposition of amyloid plaques and tangles. Age and apolipoprotein E allele E4 are two strong risk factors for AD, but few data are still available on their effect on CSF markers in normal aging. OBJECTIVE: To study the effect of age on CSF Abeta42, total tau, and p-tau levels in a well-characterized group of cognitively normal subjects. METHODS: CSF Abeta42 levels of 81 subjects (27% female, 53 +/- 15.3 years, range: 21-88) were determined with sandwich enzyme-linked immunosorbent assay; of these, total tau and p-tau levels were measured in 61 (75%) and 42 (52%) cases, respectively. A linear regression analysis between age and CSF markers was carried out on the whole sample and separately in apolipoprotein E allele E4 carriers and noncarriers. RESULTS: The median levels of all markers were significantly different between young (<65 years) and old (>=65 years) subjects (Abeta42: P = .03; tau: P = .02; p-tau: P = .002; tau/Abeta42: P = .004; p-tau/Abeta42: P = .03). The association of marker levels with age was confirmed in linear regression models, where a positive relationship with age was observed for total tau (B = 2.3; 95% confidence interval [CI]: 0.89 to 3.7; P = .002), p-tau (B = 0.5; 95% CI: 0.1 to 0.9; P = .02), and tau/Abeta42 ratio (B = 0.006; 95% CI: 0.002 to 0.01; P = .002). No subjects showed abnormal tau, whereas 19% showed abnormal CSF Abeta42 concentrations. CONCLUSION: In cognitively normal subjects, the concentrations of CSF biomarkers of AD are associated with age. Further longitudinal studies could clarify whether Abeta42 low levels represent a preclinical AD biomarker. PMID- 22677493 TI - Screening nonrandomized studies for medical systematic reviews: a comparative study of classifiers. AB - OBJECTIVES: To investigate whether (1) machine learning classifiers can help identify nonrandomized studies eligible for full-text screening by systematic reviewers; (2) classifier performance varies with optimization; and (3) the number of citations to screen can be reduced. METHODS: We used an open-source, data-mining suite to process and classify biomedical citations that point to mostly nonrandomized studies from 2 systematic reviews. We built training and test sets for citation portions and compared classifier performance by considering the value of indexing, various feature sets, and optimization. We conducted our experiments in 2 phases. The design of phase I with no optimization was: 4 classifiers * 3 feature sets * 3 citation portions. Classifiers included k nearest neighbor, naive Bayes, complement naive Bayes, and evolutionary support vector machine. Feature sets included bag of words, and 2- and 3-term n-grams. Citation portions included titles, titles and abstracts, and full citations with metadata. Phase II with optimization involved a subset of the classifiers, as well as features extracted from full citations, and full citations with overweighted titles. We optimized features and classifier parameters by manually setting information gain thresholds outside of a process for iterative grid optimization with 10-fold cross-validations. We independently tested models on data reserved for that purpose and statistically compared classifier performance on 2 types of feature sets. We estimated the number of citations needed to screen by reviewers during a second pass through a reduced set of citations. RESULTS: In phase I, the evolutionary support vector machine returned the best recall for bag of words extracted from full citations; the best classifier with respect to overall performance was k-nearest neighbor. No classifier attained good enough recall for this task without optimization. In phase II, we boosted performance with optimization for evolutionary support vector machine and complement naive Bayes classifiers. Generalization performance was better for the latter in the independent tests. For evolutionary support vector machine and complement naive Bayes classifiers, the initial retrieval set was reduced by 46% and 35%, respectively. CONCLUSIONS: Machine learning classifiers can help identify nonrandomized studies eligible for full-text screening by systematic reviewers. Optimization can markedly improve performance of classifiers. However, generalizability varies with the classifier. The number of citations to screen during a second independent pass through the citations can be substantially reduced. PMID- 22677494 TI - Formulating latent growth using an explanatory item response model approach. AB - In this paper, we present a way to extend the Hierarchical Generalized Linear Model (HGLM; Kamata (2001), Raudenbush (1995)) to include the many forms of measurement models available under the formulation known as the Random Coefficients Multinomial Logit (MRCML) Model (Adams, Wilson and Wang, 1997), and apply that to growth modeling. First, we review two different traditions in modeling growth studies: the first is based in the hierarchical linear modeling (HLM) tradition, and the second, which is the topic of this paper, is rooted in the Rasch measurement tradition - this is the linear Latent Growth Item Response Model (LG-IRM). Going beyond the linear case, the LG-IRM approach allows us to considerably extend the range of models available in the HLM tradition to incorporate several of the extensions of IRT models that are used in creating explanatory item response models (EIRM; De Boeck and Wilson, 2004). We next present a number of extensions - including polynomial growth modeling, differential item functioning (DIF) effects, growth functions that can be approximated by polynomial expressions, provision for polytomous responses, person and item covariates (and time varying covariates), and multiple dimensions of growth. We provide two empirical examples to illustrate several of the models, using the ConQuest software (Wu, Adams, Wilson and Haldane, 2008) to carry out the analyses. We also provide several simulations to investigate the success of the estimation procedures. PMID- 22677495 TI - Using the Mixed Rasch Model to analyze data from the beliefs and attitudes about memory survey. AB - In this study, we used the Mixed Rasch Model (MRM) to analyze data from the Beliefs and Attitudes About Memory Survey (BAMS; Brown, Garry, Silver, and Loftus, 1997). We used the original 5-point BAMS data to investigate the functioning of the "Neutral" category via threshold analysis under a 2-class MRM solution. The "Neutral" category was identified as not eliciting the model expected responses and observations in the "Neutral" category were subsequently treated as missing data. For the BAMS data without the "Neutral" category, exploratory MRM analyses specifying up to 5 latent classes were conducted to evaluate data-model fit using the consistent Akaike information criterion (CAIC). For each of three BAMS subscales, a two latent class solution was identified as fitting the mixed Rasch rating scale model the best. Results regarding threshold analysis, person parameters, and item fit based on the final models are presented and discussed as well as the implications of this study. PMID- 22677496 TI - An examination of personality characteristics related to acquiescence. AB - Acquiescence, the tendency to agree with statements regardless of content, is often a concern when administering self-report instruments. While there is evidence to support acquiescence as a response style, this reporting tendency may be related to personality factors of individuals. Using a sample of 757 adults, we investigated the Rosenberg Self-Esteem Scale for acquiescence response tendencies by applying the Rasch partial credit model. Results suggested that favorable (i.e., Agree or Strongly Agree) responses were more frequent for the positively worded items than for negatively worded items. Second, the relationship between acquiescence and seven additional personality measures was examined overall and by sex. Among females, acquiescence was correlated with personality measures measuring perceptions by others, whereas acquiescence among males was related to exhibition types of behaviors. PMID- 22677497 TI - Construction and validation of two parent-report scales for the evaluation of early intervention programs. AB - The State Performance Plan (SPP) developed under the 2004 reauthorization of the Individuals with Disabilities Education Act (IDEA 2004, Public Law 108-446) requires states to collect data and report on the impact of early intervention services on three key outcomes for participating families. The NCSEAM Impact on Family Scale (NIFS) and the NCSEAM Family Centered Services Scale (NFCSS) were developed to provide states with a means to address this new reporting requirement and to collect additional data that would inform program improvement efforts. Items suggested by stakeholder groups were piloted with a nationally representative sample of parents of children with developmental delays or disabilities ages birth to three participating in early intervention services in eight states. The 28-item NIFS had measurement reliabilities ranging from .93-.96 in a sample of 1,750; measurement reliabilities for the 135-item NFCSS ranged from .94 to .97 in a sample of 1,755 respondents. A 29-item version of the NFCSS had measurement reliabilities ranging from .87 to .92. Using data from the pilot study, stakeholders established a recommended performance standard, set at a meaningful point in the NIFS item hierarchy, for each of the three established outcome areas. PMID- 22677498 TI - Multi-factor scale consolidation when theory is weak. AB - As a practical matter, Spirituality and Quality of Life in the health sciences are usually measured separately. Theoretical foundations for this distinction, however, are not strong. In this research, an empirical investigation was conducted into their joint calibration with a Rasch model. Functional Assessment of Cancer Therapy-General (28 items), a cancer health-related quality of life measure (HRQOL), and Functional Assessment of Chronic Illness - Spiritual Well Being (12 items), a measure of religious and existential well-being (Spirituality), were co-calibrated with a Rasch model implemented with WINSTEPS software for ratings from 545 breast cancer patients. The results show a hierarchical integration of QOL and Spirituality items on a common variable, and both patient separation (2.66) and reliability (.88) improve after co calibration. Principal Component Analysis of co-calibrated item residuals did not show major threats to dimensionality, and joint calibration explains item variance comparable to separate calibrations (51.9%). Although patient measures (logits) based on separate and co-calibration are within two standard errors, ethnic and racial group values shift after co-calibration. PMID- 22677499 TI - Developing an emotional distress item bank for cancer patients. AB - Emotional distress is common among cancer patients during and after treatment. Many instruments have been used to measure emotional distress; however, none of them has emerged as a standard. Although the diversity of instruments has some merit, the lack of a common measure limits our ability to compare studies. This paper describes how we constructed a 46-item emotional distress bank. Using expert judgment, we selected a pool of items with emotional content from this six instrument set. Rasch rating scale analysis helped us identify a set of general distress items with good model fit and a measurement gap causing floor effects. Additional items were written to augment the measure where found deficient. The resulting set of items reflects a spectrum of positive and negative affect. The measure demonstrated excellent reliability (person separation reliability = .96) and a wide range of emotional distress and was able to distinguish among levels of disease severity. PMID- 22677500 TI - Effect of flow rate and lead/copper pipe sequence on lead release from service lines. AB - A pilot experiment examined lead leaching from four representative configurations of service lines including: (1) 100% lead (Pb), (2) 100% copper (Cu), (3) 50% Pb upstream of 50% Cu, and (4) 50% Pb-downstream of 50% Cu using a range of flow rates. The cumulative mass of lead release indicated that a typical partial replacement configuration (50% lead downstream of copper) did not provide a net reduction in lead when compared to 100% lead pipe (85 mg for 50% Pb-downstream versus 83 mg for 100%-Pb) due to galvanic and deposition corrosion. The partially replaced service line configuration also had a much greater likelihood of producing water with "spikes" of lead particulates at higher flow rates, while tending to produce lower levels of lead at very low flow rates. After the first 214 days the galvanic current between copper and lead was only reduced by 34%, proving that galvanic impacts can be highly persistent even in water with optimized corrosion control by dosing of zinc orthophosphate. Finally, this experiment raises concern about the low flow rates used during some prior home sampling events, which may underestimate exposure to lead during normal water use, especially when galvanic Pb:Cu connections are present. PMID- 22677501 TI - Inactivation mechanisms of bacterial pathogen indicators during electro dewatering of activated sludge biosolids. AB - Electro-dewatering is an energy-efficient technology in which an electric field can increase the dryness of biosolids from secondary wastewater treatment from 15% w/w to 30-50% w/w. Here, we address bacterial pathogen indicators inactivation (total coliforms, Escherichia coli and aerobic endospores) during electro-dewatering, investigating the roles of electrochemically generated oxidants, extreme pH, and high temperature (from Joule heating). Our results demonstrate that temperature is the primary factor affecting total coliforms and E. coli inactivation. First, several electro-dewatering cycles were used to increase sludge temperature to about 100 degrees C after 6 min, during which time the average pH decreased from 7 to 3.6 after 10 min. Total coliforms and E. coli MPNs reached their detection limits after 6 min (with 4-5 logs of inactivation for total coliforms and 3-4 logs for E. coli). In contrast, aerobic endospores were not inactivated under these conditions; rather, their germination appeared to be stimulated by 6-8 min of electro-dewatering. Second, the dewatering cake was separated into four horizontal layers. After 8 min of electro dewatering, the pH in the top layers decreased to 3, whereas the pH in the bottom layers increased to 8. Inactivation of total coliforms and E. coli in the sludge cake was similar in all layers, increasing with time, suggesting that oxidants and extreme pH are secondary inactivation factors. Finally, electrodes were cooled to maintain a temperature less than 34 degrees C. Although pH decreased significantly after 12 min of electro-dewatering, there was no significant bacterial pathogen indicator inactivation at low temperature. PMID- 22677502 TI - Surface neutralization and H(2)S oxidation at early stages of sewer corrosion: influence of temperature, relative humidity and H(2)S concentration. AB - While the involvement of a range of environmental factors in sewer corrosion is known, a comprehensive understanding of the processes involved and the exact role of individual environmental factors in sewer corrosion is still lacking. The corrosion of concrete in sewer systems is reported to be initiated through chemical reactions (involving H(2)S and CO(2)) that lower the surface pH to a level then conducive for biological activity. However, the specific influence of environmental variables, such as H(2)S level, temperature, and relative humidity etc. remains unclear; although, they are expected to control these initial surface reactions of the concrete sewer pipe. We examined changes in the surface chemistry of concrete during the early stages of corrosion by exposing concrete coupons to thirty-six independent conditions in well-controlled laboratory chambers that simulated conditions typically found in various sewer environments across Australia. The conditions employed were combinations of six H(2)S levels, three gas-phase temperatures and two relative humidity levels. Our results indicate that the role of CO(2) on initial surface pH reduction is insignificant when compared to the influence of H(2)S. Within the first 12 months, a decrease in surface pH by 4.8 units was observed for coupons exposed to 30 degrees C and 50 ppm H(2)S, while significantly lower pH reductions of 3.5 and 1.8 units were detected for coupons exposed to 25 degrees C and 18 degrees C respectively, and 50 ppm H(2)S. Elemental sulphur was found to be the major oxidation product of H(2)S and elevated concentrations were detected at the higher levels of H(2)S, temperature and relative humidity. More significantly, the data obtained from the controlled chamber experiments correlated with those obtained from the field exposed coupons. Hence, these findings can be extended to real sewer corrosion processes. PMID- 22677503 TI - Physical and mechanical degradation of shirting fabrics in burial conditions. AB - The current focal areas within forensic textile science are fibre identification and assessment of the method of damage to fabrics. This paper investigates fabric degradation within clandestine burials. The fabrics considered in this paper, unlike previous archaeological studies, are a modern polyester-cotton blend (65%/35%) and a 100% cotton fabric both of which are commonly used for men's shirting fabrics in the UK. Three laundering conditions were investigated (i) not laundered, (ii) laundered 6 times, and (iii) laundered 60 times; this represented varying conditions of fabric upon clothing deposition. The two burial conditions; sand and clay, were selected as extremes of soil type. The deposition times (15 and 30 days) were based on a study of clandestine burials in UK crimes. There were clear differences in how polyester-cotton and cotton stained within the two different soil conditions, polyester-cotton becoming extensively stained after a 30-day deposition in sand. The tear force required to tear the fabric after deposition, suggested that polyester/cotton fabrics were consistently weaker after burial, regardless of soil type and deposition period. There was also significant damage caused to not-laundered cotton fabrics after a 30-day deposition in clay. This work indicates that common apparel fabrics can degrade in relatively short times when buried. PMID- 22677504 TI - Does surgical volume affect outcome after primary and revision knee arthroplasty? A systematic review of the literature. AB - BACKGROUND: In 2009 there were 72,980 primary and 4565 revision knee arthroplasties performed in England and Wales [1]. Given the large number of procedures done annually any factors that may influence outcome and benefit the patient must be considered seriously. OBJECTIVES: To find out whether a relationship exists between hospital and surgical volume and patient outcomes for primary and revision knee arthroplasty. A systematic review of the literature was performed to evaluate the current evidence using the PRISMA criteria [2]. DATA SOURCES: A computerised literature search was performed on the electronic databases PubMed, Medline, Embase and CINAHL between 1973 and 2011. STUDY ELIGIBILITY CRITERIA: All abstracts, in the English language, pertaining to either surgical or hospital volume and outcome after primary and revision knee arthroplasty between 1973 and 2011 were considered. Outcomes of interest included morbidity, mortality, clinical and economic outcomes. CONCLUSIONS: Both the orthopaedic and surgical specialties literature demonstrates a clear and consistent relationship between both surgeon and hospital volume with outcome, higher volume being associated with improved patient outcomes. In view of the literature consideration should be given to whether all orthopaedic operations should be carried out by all surgeons in all hospitals. PMID- 22677505 TI - Neuroradiology can predict the development of hand function in children with unilateral cerebral palsy. AB - BACKGROUND: Much variation is found in the development of hand function in children with unilateral cerebral palsy (CP). OBJECTIVE: . To explore how anatomic brain abnormalities can be used to predict the development of hand function. METHODS: A total of 32 children with unilateral CP (16 boys and 16 girls) were evaluated at least once a year by the Assisting Hand Assessment (AHA). The data collection covered an age range from 18 months to 8 years (mean time in study, 4 years and 6 months). Computerized tomography or magnetic resonance imaging of the brain were assessed for patterns of brain damage, including the location of gray and extent of white-matter damage. The children were divided into groups according to lesion characteristics, and a series of univariate models were analyzed with a nonlinear mixed-effects model. The rate and maximum limit of development were calculated. RESULTS: The highest predictive power of better development of hand function was the absence of a concurrent lesion to the basal ganglia and thalamus, independent of the basic type of brain lesion. This model predicted both the rate of increasing ability and hand function at age 8 years. Hand function was also predicted by the basic pattern of damage and by the extent of white-matter damage. The presence of unilateral or bilateral damage had no predictive value. CONCLUSIONS: Neuroradiological findings can be used to make a crude prediction of the future development of the use of the affected hand in young children with unilateral CP. PMID- 22677506 TI - An ovarian endometriotic cyst in a patient with prepubertal hypopituitarism due to a craniopharyngioma: a clue for endometrioma pathogenesis. PMID- 22677507 TI - Delivery of a healthy baby following more than 17 years of pronuclear stage embryos cryopreservation. PMID- 22677508 TI - Anal human papillomavirus DNA in women at a colposcopy clinic. AB - OBJECTIVES: To describe the type-specific prevalence of anal and cervical human papillomavirus (HPV) infections and the cytology in HIV-negative women without a history of cervical cancer, attending a colposcopy clinic. To examine if an HPV positive anal smear is related to anal pathology and consequently indicative for further examinations (high resolution anoscopy, anal biopsy). STUDY DESIGN: From 149 consecutive women an anal swab and a cervical swab were taken, using the Cervex-Brush. The presence of 18 different HPV genotypes was determined using TaqMan-based real-time quantitative PCR targeting type-specific sequences of viral genes. From the fluid containing the cellular material, a liquid-based cytology sample was prepared of both collections with the robotic BD PrepStain Slide Processor. All slides were pre-screened by BD FocalPoint system and categorized from quintiles 1 to 5 and afterwards screened using targeted microscopic interpretation of selected suspicious fields using FocalPoint guided screening review stations. The 2001 Bethesda System Terminology was used for the anal slides. RESULTS: Ninety-six anal samples and all 149 cervical samples were adequate. Overall presence of HPV in the anus was 56.3% and in the cervix 53.7%. Overall, cytological abnormalities were found in 10.8% of anal smears and in 32.8% of cervical smears. HPV genotypes were identified in 47 samples on both sites: partial or complete concordance was found in 85.1%. HPV types 6, 16 and 18 were found in 27.9% and in 26.6% of the anal and cervical samples, respectively. The top three HPV types in the anus were 16, 51 and 39; in the cervix 16, 39, 51 and 56 (a shared 3(rd) place). HPV type 11 was not found. CONCLUSIONS: The presence of HPV genotypes is clearly multifocal in this study population of women attending a colposcopy clinic, with high concordance of genotypes. The number of anal HPV infections is high. Although cytological abnormalities are rare, the presence of HPV may lead to anal lesions later in life. From this perspective, complementary medical history and clinical examination of the anal region are advised. PMID- 22677509 TI - Secreted cyclophilin A induction during embryo implantation in a model of human trophoblast-endometrial epithelium interaction. AB - OBJECTIVE: Embryo implantation in the human is a complex process that is crucial for a successful pregnancy. Implantation involves complex interactions between the embryo and the maternal endometrium. In order to understand the critical events involved in human embryo implantation, we established a human trophoblast endometrial interaction model to study the putative alterations of gene expression during implantation. STUDY DESIGN: Comparative proteomic analysis was applied to the co-culture and separated culture systems of the trophoblast cell line BeWo and human endometrial epithelial cell (EEC) line RL95-2. Comparing the secreted molecules resulted in an interesting finding that secreted cyclophilin A (CypA) was increased in the co-culture system. To further verify our observation, human recombinant CypA was applied to endometrial cells to understand the downstream gene regulation. RESULTS: Cyclophilin A (CypA) was identified by MALDI TOF Mass with higher expression levels in the co-cultured cells when compared to the endometrial cells alone. Western blot analysis further confirmed the increased expression of CypA in co-culture conditions. Immunoblotting analysis showed that both p38 MAPK and extracellular signal-regulated kinase (ERK) were activated in EEC. CONCLUSION: Our results suggest that the secreted CypA plays a specific role in the signaling pathway of embryo implantation. The identification of CypA opens a new avenue for early embryo implantation research. PMID- 22677510 TI - Development of a repeated-dose liver micronucleus assay using adult rats: an investigation of diethylnitrosamine and 2,4-diaminotoluene. AB - Various liver micronucleus assay methods, such as those involving partial hepatectomy, treatment with mitogens, and the use of juvenile animals, have been developed. These assays have been proven to be of high sensitivity and specificity to predict hepatocarcinogenicity of compounds that cannot be detected by bone marrow micronucleus assays. On the contrary, the existing assays have only been evaluated for their use in detecting micronucleus induction in the settings of relatively short-term cell proliferation. However, the integration of in vivo genotoxicity endpoints into routine toxicity studies is increasingly desired from the viewpoint of animal welfare to reduce the number of animals used. In the present study, the rodent hepatocarcinogens diethylnitrosamine (DEN) and 2,4-diaminotoluene (2,4-DAT) were repeatedly administered orally to male Crl:CD (SD) rats (6 weeks old at the beginning of administration) for 5, 14, and 28 days, and changes in the frequency of hepatocytes with micronuclei in liver tissues that had undergone no artificial treatment to accelerate cell proliferation were evaluated. At the same time, a new method of hepatocyte isolation involving the treatment of a portion of the liver with collagenase in a centrifuge tube, without the use of in situ perfusion, was established. The induction of micronucleated hepatocytes was achieved after the repeated administration of DEN for 5 days or longer and of 2,4-DAT for 14 days or longer. Micronucleus frequencies were increased depending on the number of administrations, indicating that micronucleated hepatocytes had possibly remained for a long period of time and accumulated additively. It therefore appears that even in adult rat liver with low mitotic activity, a repeated-dose of a chemical substance for 14 days or longer enables the detection of micronucleus induction. In addition, the establishment of a method to isolate hepatocytes without perfusion using only a part of the liver enables the integration of liver micronucleus assays into general toxicity studies. PMID- 22677511 TI - Neoadjuvant hormone therapy for radical prostate radiotherapy: bicalutamide monotherapy vs. luteinizing hormone-releasing hormone agonist monotherapy: a single-institution matched-pair analysis. AB - BACKGROUND: The purpose of this study was to compare the prostate-specific antigen (PSA) response to either neoadjuvant bicalutamide (BC) monotherapy or neoadjuvant luteinizing hormone-releasing hormone agonist (LHRHa) monotherapy and the subsequent effect on biochemical failure-free survival (BFFS) in men receiving radical radiotherapy (RT) for localized prostate cancer. PATIENTS AND METHODS: This was a retrospective review of consecutive men treated with BC monotherapy before radical prostate RT who were individually case-matched to men treated with neoadjuvant LHRHa monotherapy. PSA kinetics and absolute pre-RT posthormone PSA (PRPH-PSA) level and subsequent BFFS were analyzed. RESULTS: Sixty-five men treated with BC monotherapy with a median follow-up of 44 months were individually matched with 65 men treated with LHRHa with a median follow-up of 54 months. Statistically significant differences were noted between groups in the PRPH-PSA, with a mean of 2.9 ng/mL (0.1-11.2 ng/mL) for patients receiving BC treatment and 1.8 ng/mL (0.1-11.1 ng/mL) for patients receiving LHRHa treatment (P < .001). A PRPH-PSA of < 1.0 and < 0.1 ng/mL was seen in 16 (24.6%) and 2 (3%) of the patients receiving BC and 34 (52.3%) and 3 (4.6%) patients receiving LHRHa, respectively. There were no significant differences between groups in either PSA halving time or velocity. Phoenix biochemical failure occurred in 10 (15.4%) and 8 (12.3%) patients receiving BC and patients receiving LHRHa, respectively. Neither PRPH-PSA level nor PSA kinetics during the neoadjuvant period predict for subsequent BFFS at this duration of follow-up. CONCLUSIONS: Although neoadjuvant BC therapy did not result in equivalent PRPH-PSA suppression when compared with neoadjuvant LHRHa alone, there was no difference in biochemical failure rates between cohorts at 50 months' median follow-up. Longer follow-up is required. PMID- 22677512 TI - Comment on: School based health centers in an era of health care reform: building on history. Victoria Keeton, RN, MS, CPNP, CNS, Samira Soleimanpour, MPH, Claire D. Brindis, DrPH. Foreword. PMID- 22677515 TI - Interview with "Ms. Rob," health educator at San Lorenzo High School Health Center. Interview by Naomi Schapiro. PMID- 22677513 TI - School-based health centers in an era of health care reform: building on history. AB - School-based health centers (SBHCs) provide a variety of health care services to youth in a convenient and accessible environment. Over the past 40 years, the growth of SBHCs evolved from various public health needs to the development of a specific collaborative model of care that is sensitive to the unique needs of children and youth, as well as to vulnerable populations facing significant barriers to access. The SBHC model of health care comprises of on-school site health care delivery by an interdisciplinary team of health professionals, which can include primary care and mental health clinicians. Research has demonstrated the SBHCs' impacts on delivering preventive care, such as immunizations; managing chronic illnesses, such as asthma, obesity, and mental health conditions; providing reproductive health services for adolescents; and even improving youths' academic performance. Although evaluation of the SBHC model of care has been complicated, results have thus far demonstrated increased access to care, improved health and education outcomes, and high levels of satisfaction. Despite their proven success, SBHCs have consistently faced challenges in securing adequate funding for operations and developing effective financial systems for billing and reimbursement. Implementation of health care reform (The Patient Protection and Affordable Care Act [P.L. 111-148]) will profoundly affect the health care access and outcomes of children and youth, particularly vulnerable populations. The inclusion of funding for SBHCs in this legislation is momentous, as there continues to be increased demand and limited funding for affordable services. To better understand how this model of care has and could further help promote the health of our nation's youth, a review is presented of the history and growth of SBHCs and the literature demonstrating their impacts. It may not be feasible for SBHCs to be established in every school campus in the country. However, the lessons learned from the synergy of the health and school settings have major implications for the delivery of care for all providers concerned with improving the health and well-being of children and adolescents. PMID- 22677516 TI - The Bellevue/Norman Thomas High School based health center: student perspectives. PMID- 22677517 TI - Bacillus strains isolated from rhizosphere showed plant growth promoting and antagonistic activity against phytopathogens. AB - Seven bacterial isolates screened from rhizosphere of common bean growing at Uttarakhand Himalaya showed potential plant growth promoting (PGP) and antagonistic activities. Based on 16S rRNA gene sequence the isolate BPR7 was identified as Bacillus sp. BPR7. The strain BPR7 produced IAA, siderophore, phytase, organic acid, ACC deaminase, cyanogens, lytic enzymes, oxalate oxidase, and solubilized various sources of organic and inorganic phosphates as well as potassium and zinc. Strain BPR7 strongly inhibited the growth of several phytopathogens such as Macrophomina phaseolina, Fusarium oxysporum, F. solani, Sclerotinia sclerotiorum, Rhizoctonia solani and Colletotricum sp. in vitro. Cell free culture filtrate of strain BPR7 also caused colony growth inhibition of all test pathogens. PGP and antifungal activities of Bacillus sp. BPR7 suggest that it may be exploited as a potential bioinoculant agent for P. vulgaris. PMID- 22677518 TI - A high-yielding synthesis of allyl glycosides from peracetylated glycosyl donors. AB - beta-Configured peracetylated sugars are often used as easily accessible glycosyl donors that are typically activated with common Lewis acids such as boron trifluoride or trimethylsilyltrifluoromethane sulfonate. Often these glycosylations occur with unsatisfactory yields due to incomplete reactions or extensive byproduct formation, primarily as a result of loss of an additional acetyl group generating partially unprotected glycosides. Here we report a simple glycosylation-reacetylation protocol for the generation of predominantly beta configured peracetylated allyl glucoside, -galactoside, -lactoside, and maltoside with substantially improved reaction yields. PMID- 22677519 TI - Effect of 6-O-alpha-maltosyl-beta cyclodextrin and its cholesterol inclusion complex on cellular cholesterol levels and ABCA1 and ABCG1 expression in mouse mastocytoma P-815 cells. AB - We have previously described 6-O-alpha-maltosyl-beta cyclodextrin (Mal-betaCD), which forms soluble inclusion complex with cholesterol. Here we further investigated the effect of Mal-betaCD and cholesterol/Mal-betaCD inclusion complex (CLM) on cellular cholesterol levels in a mouse mast cell line, mastocytoma P-815 cells (P-815 cells). Mal-betaCD removes cellular cholesterol forming inclusion complexes, while Mal-betaCD-induced lack of cellular cholesterol was replenished by the addition of CLM without cytotoxicity. Reduction and replenishment of cellular cholesterol in Mal-betaCD- and/or CLM treated P-815 cells, respectively, were demonstrated by LC/MS and fluorescence microscopy with filipin III. CLM rather than free Mal-betaCD and free cholesterol was efficiently incorporated into P-815 cells and its incorporation was inhibited by incubation at low temperature, or with sodium azide and cytochalasin D. P-815 cells have been confirmed to express ATP-binding cassette (ABC) transporters, ABCA1, ABCG1, and P-glycoprotein (P-gp), by Western blot and mRNA analysis. Cholesterol reduction by Mal-betaCD abolishes the mRNA and protein expression of ABCA1 and ABCG1, but not of P-gp. Cholesterol loading by CLM restores the diminished ABCA1 and ABCG1 mRNA expression in Mal-betaCD-treated P-815 cells. However, both Mal-betaCD and CLM had no effect on P-gp activity measured by the rhodamine 123 efflux assay. These results indicate that alteration of cholesterol levels with Mal-betaCD or CLM led to down- or up-regulation of ABCA1 and ABCG1 expression in P-815 cells. PMID- 22677520 TI - A novel mechanism for emulating insect wing kinematics. AB - A novel dual-differential four-bar flapping mechanism that can accurately emulate insect wing kinematics in all three degrees of freedom (translation, rotation and stroke plane deviation) is developed. The mechanism is specifically designed to be simple and scalable such that it can be utilized on an insect-based flapping wing micro air vehicle. Kinematic formulations for the wing stroke position, pitch angle and coning angle for this model are derived from first principles and compared with a 3D simulation. A benchtop flapping mechanism based on this model was designed and built, which was also equipped with a balance for force measurements. 3D motion capture tests were conducted on this setup to demonstrate the capability of generating complex figure-of-eight flapping motions along with dynamic pitching. The dual-differential four-bar mechanism was implemented on a light-weight vehicle that demonstrated tethered hover. PMID- 22677521 TI - Characterization of silver release from commercially available functional (nano)textiles. AB - Silver, both in the nano as well as in other forms, is used in many applications including antimicrobial textiles. Washing of such textiles has already been identified as an important process that results in the release of silver into wastewater. This study thus investigated the release of silver from eight different commercially available silver-textiles during a washing and rinsing cycle. The silver released was size-fractionated and characterized using electron microscopy. In addition, the antimicrobial functionality of the textiles was tested before and after washing. Three of the textiles contained nanosized silver (labeled or confirmed by manufacturers' information), another used a metallic silver wire and four contained silver in undeclared form. The initial silver content of the textiles was between 1.5 and 2925mg Ag/kg. Only four of the investigated textiles leached detectable amounts of silver, of which 34-80% was in the form of particles larger than 450nm. Microscopic analysis of the particles released in the washing solutions identified Ti/Si-AgCl nanocomposites, AgCl nanoparticles, large AgCl particles, nanosilver sulfide and metallic nano-Ag, respectively. The nanoparticles were mainly found in highly agglomerated form. The identified nanotextiles showed the highest antimicrobial activity, whereas some of the other textiles, e.g. the one with a silver wire and the one with the lowest silver content, did not reduce the growth of bacteria at all. The results show that different silver textiles release different forms of silver during washing and that among the textiles investigated AgCl was the most frequently observed chemical form in the washwater. PMID- 22677522 TI - Water pressure head and temperature impact on isoxaflutole degradation in crop residues and loamy surface soil under conventional and conservation tillage management. AB - Laboratory incubations were performed in order to evaluate the dissipation of the proherbicide isoxaflutole in seedbed layer soil samples from conventional and conservation tillage systems and in maize and oat residues left at the soil surface under conservation tillage. The effects of temperature and water pressure head on radiolabelled isoxaflutole degradation were studied for each sample for 21d. Mineralisation of isoxaflutole was low for all samples and ranged from 0.0% to 0.9% of applied (14)C in soil samples and from 0.0% to 2.4% of applied (14)C in residue samples. In soil samples, degradation half-life of isoxaflutole ranged from 9 to 26h, with significantly higher values under conservation tillage. In residue samples, degradation half-life ranged from 3 to 31h, with significantly higher values in maize residues, despite a higher mineralisation and bound residue formation than in oat residues. Whatever the sample, most of the applied (14)C remained extractable during the experiment and, after 21d, less than 15% of applied (14)C were unextractable. This extractable fraction was composed of diketonitrile, benzoic acid derivative and several unidentified metabolites, with one of them accounting for more than 17% of applied (14)C. This study showed that tillage system design, including crop residues management, could help reducing the environmental impacts of isoxaflutole. PMID- 22677523 TI - Altered toxicity of organic pollutants in water originated from simultaneous exposure to UV photolysis and CdSe/ZnS quantum dots. AB - The paper reports unforeseen results of increased toxicity of water, subsequent to interactions between CdSe/ZnS quantum dots (QDs), phenol and toluene under UV irradiation. The consistent pattern of changes in measured toxicity (TU) was observed and correlated with degradation of phenol and/or toluene. Spearman rank coefficients (SRCs) for data pairs sum-parameters vs. TU were calculated. The highest correlation between toxicity and degradation by-products was observed for hydroquinone (0.86) and catechol (0.89). The presence of QDs in tested concentration range in the absence of UV has shown low toxicity and no interactions with phenol and/or toluene. The leak of constituent core and shell metal ions was observed. The minor differences in physical characteristics of tested QDs of the same chemical composition led to rather different degradation patterns of phenol and toluene, and the amount of leak of the metal ions as well. PMID- 22677525 TI - Reliability of a treatment-based classification system for subgrouping people with low back pain. AB - STUDY DESIGN: Observational, cross-sectional reliability study. OBJECTIVES: To examine the interrater reliability of novice raters in their use of the treatment based classification (TBC) system for low back pain and to explore the patterns of disagreement in classification errors. BACKGROUND: Although the interrater reliability of individual test items in the TBC system is moderate to good, some error persists in classification decision making. Understanding which classification errors are common could direct further refinement of the TBC system. METHODS: Using previously recorded patient data (n = 24), 12 novice raters classified patients according to the TBC schema. These classification results were combined with those of 7 other raters, allowing examination of the overall agreement using the kappa statistic, as well as agreement/disagreement among pairwise comparisons in classification assignments. A chi-square test examined differences in percent agreement between the novice and more experienced raters and differences in classification distributions between these 2 groups of raters. RESULTS: Among 12 novice raters, there was 80.9% agreement in the pairs of classification (kappa = 0.62; 95% confidence interval: 0.59, 0.65) and an overall 75.5% agreement (kappa = 0.57; 95% confidence interval: 0.55, 0.69) for the combined data set. Raters were least likely to agree on a classification of stabilization (77.5% agreement). The overall percentage of pairwise classification judgments that disagreed was 24.5%, with the most common disagreement being between manipulation and stabilization (11.0%), followed by a mismatch between stabilization and specific exercise (8.2%). CONCLUSION: Additional refinement is needed to reduce rater disagreement that persists in the TBC decision-making algorithm, particularly in the stabilization category. J Orthop Sports Phys Ther 2012;42(9):797-805, Epub 7 June 2012. doi:10.2519/jospt.2012.4078. PMID- 22677524 TI - Antimicrobial activity of metal oxide nanoparticles supported onto natural clinoptilolite. AB - The antimicrobial activity of Cu(2)O, ZnO and NiO nanoparticles supported onto natural clinoptilolite was investigated in the secondary effluent under dark conditions. After 24h of contact the Cu(2)O and ZnO nanoparticles reduced the numbers of viable bacterial cells of Escherichia coli and Staphylococcus aureus in pure culture for four to six orders of magnitude and showed consistent 100% of antibacterial activity against native E. coli after 1h of contact during 48 exposures. The antibacterial activity of NiO nanoparticles was less efficient. The Cu(2)O and NiO nanoparticles showed 100% of antiprotozoan activity against Paramecium caudatum and Euplotes affinis after 1h of contact, while ZnO nanoparticles were less efficient. The morphology and crystallinity of the nanoparticles were not affected by microorganisms. The metal oxide nanoparticles could find a novel application in the disinfection of secondary effluent and removal of pathogenic microorganisms in the tertiary stage of wastewater treatment. PMID- 22677526 TI - Malignant mucosal melanoma in the olfactory cleft of a 10-year-old child. AB - Mucosal malignant melanoma is a rare but aggressive neoplasm with high rates of recurrence and death. It is known that two-thirds of mucosal melanoma cases arise in the nasal cavity and paranasal sinuses in adults. However, there have been few studies until now on children with mucosal malignant melanoma and the related treatment. We report on a 10-year-old girl with mucosal malignant melanoma presented as a nasal polyp, which was removed via endoscopic sinus surgery and adjuvant chemotherapy without recurrence. PMID- 22677527 TI - Deconstructing 14-phenylpropyloxymetopon: minimal requirements for binding to mu opioid receptors. AB - A series of phenylpropyloxyethylamines and cinnamyloxyethylamines were synthesized as deconstructed analogs of 14-phenylpropyloxymetopon and analyzed for opioid receptor binding affinity. Using the Conformationally Sampled Pharmacophore modeling approach, we discovered a series of compounds lacking a tyrosine mimetic, historically considered essential for MU opioid binding. Based on the binding studies, we have identified the optimal analogs to be N-methyl-N phenylpropyl-2-(3-phenylpropoxy)ethanamine, with 1520 nM, and 2-(cinnamyloxy)-N methyl-N-phenethylethanamine with 1680 nM affinity for the MU opioid receptor. These partial opioid structure analogs will serve as the novel lead compounds for future optimization studies. PMID- 22677528 TI - Systematic SAR study of the side chain of nonsecosteroidal vitamin D3 analogs. AB - A series of nonsecosteroidal vitamin D(3) analogs with carboxylic acid were explored. Through our systematic SAR studies on the side chain moiety, compound 6b was identified as the optimal compound showing excellent vitamin D receptor (VDR) agonistic activity. Compound 6b had the diethyl group in the terminal which was bound by (E)-olefin linker to the bisphenyl core. Calculating the volume of the side chain showed that the diethyl group in 6b filled the hydrophobic region of VDR with the ideal packing coefficient based on the 55% rule, and that this resulted in the most potent in vitro activity. PMID- 22677529 TI - Pyrrolidinobenzoic acid inhibitors of influenza virus neuraminidase: the hydrophobic side chain influences type A subtype selectivity. AB - Neuraminidase (NA) plays a critical role in the life cycle of influenza virus and is a target for new therapeutic agents. A series of influenza neuraminidase inhibitors with the pyrrolidinobenzoic acid scaffold containing lipophilic side chains at the C3 position have been synthesized and evaluated for influenza neuraminidase inhibitory activity. The size and geometry of the C3 side chains have been modified in order to investigate structure-activity relationships. The results indicated that size and geometry of the C3-side chain are important for selectivity of inhibition against N1 versus N2 NA, important type A influenza variants that infect man, including the highly lethal avian influenza. PMID- 22677530 TI - The secret life of Bcl-2: apoptosis-independent inhibition of DNA repair by Bcl-2 family members. AB - Programmed cell death and DNA repair are two fundamental biological processes that play essential roles in cell fate and genetic transmission. The canonical role of Bcl-2 family members is the regulation of programmed cell death. Strikingly, numerous studies from different laboratories have shown that although Bcl-2 increases cell survival, it also inhibits all DNA repair systems, resulting in genome instability/variability. Bcl-2 affects the mechanistically distinct DNA repair systems via different mechanisms. These effects are generally independent of the regulation of apoptosis, revealing additional roles for Bcl-2. The targets of Bcl-2 include APE1, MSH2, PARP1, Ku70 and the oncosuppressor BRCA1. Targetting BRCA1 should be of particular importance because this might impact many essential cellular processes in which BRCA1 is involved, including homologous recombination (HR), non-homologous end joining (NHEJ), base excision repair, cell-cycle regulation, cell death, ubiquitination, inactivation of the X-chromosome, transcription, and protein translation. Beside the pathological consequences, inhibition of DNA repair by Bcl-2 can be, in contrast, advantageously used in some physiological situations: (1) repression of excessive unschedule HR, thus protecting against the accumulation of toxic HR intermediates and HR-dependent genome rearrangements; (2) inhibition of NHEJ might protect against retrovirus integration; (3) it has been proposed that inhibition of mismatch repair might also favors hypermutation at immunoglobulin genes. Finally, because Bcl-2 affects the maintenance of genome stability, one can suggest Bcl-2 might play a role in molecular evolution. Bcl-2 family members control cell death through complex stochiometric equilibriums. Incorporating DNA repair proteins to such an elaborate network should allow for a fine tuning of the coordinated control of cell viability and genetic stability/instability. Relationships between DNA repair and regulation of cell death represent exciting challenges for future prospects and are essential for the development of promising new strategies against cancer. PMID- 22677531 TI - Ionizing radiation biomarkers for potential use in epidemiological studies. AB - Ionizing radiation is a known human carcinogen that can induce a variety of biological effects depending on the physical nature, duration, doses and dose rates of exposure. However, the magnitude of health risks at low doses and dose rates (below 100mSv and/or 0.1mSvmin(-1)) remains controversial due to a lack of direct human evidence. It is anticipated that significant insights will emerge from the integration of epidemiological and biological research, made possible by molecular epidemiology studies incorporating biomarkers and bioassays. A number of these have been used to investigate exposure, effects and susceptibility to ionizing radiation, albeit often at higher doses and dose rates, with each reflecting time-limited cellular or physiological alterations. This review summarises the multidisciplinary work undertaken in the framework of the European project DoReMi (Low Dose Research towards Multidisciplinary Integration) to identify the most appropriate biomarkers for use in population studies. In addition to logistical and ethical considerations for conducting large-scale epidemiological studies, we discuss the relevance of their use for assessing the effects of low dose ionizing radiation exposure at the cellular and physiological level. We also propose a temporal classification of biomarkers that may be relevant for molecular epidemiology studies which need to take into account the time elapsed since exposure. Finally, the integration of biology with epidemiology requires careful planning and enhanced discussions between the epidemiology, biology and dosimetry communities in order to determine the most important questions to be addressed in light of pragmatic considerations including the appropriate population to be investigated (occupationally, environmentally or medically exposed), and study design. The consideration of the logistics of biological sample collection, processing and storing and the choice of biomarker or bioassay, as well as awareness of potential confounding factors, are also essential. PMID- 22677532 TI - Evidence-based treatment of jellyfish stings in North America and Hawaii. AB - We performed a systematic review of the evidence supporting various treatments for envenomation by jellyfish (cnidarian) and related organisms in North America and Hawaii. Our review produced 19 pertinent primary articles. Current research demonstrates variable response to treatment, often with conflicting results according to species studied, which contributes to considerable confusion about what treatment is warranted and efficacious. Our review suggests that vinegar causes pain exacerbation or nematocyst discharge in the majority of species. Hot water and topical lidocaine appear more widely beneficial in improving pain symptoms and are preferentially recommended. Unfortunately, they may be difficult to obtain at the site of envenomation, such as the beach or diving sites. In these instances, removing the nematocysts and washing the area with saltwater may be considered. If the envenomation is thought to be due to the bluebottle (Physalia), vinegar may be beneficial. PMID- 22677533 TI - From rags to riches: the atrial fibrillation story. PMID- 22677535 TI - Exposure to CT scans in children slightly increases risk of leukaemia or brain tumour, study shows. PMID- 22677536 TI - Cooling tower is suspected as source of legionella outbreak. PMID- 22677537 TI - Main taste effects on swallowing apnea duration in healthy adults. AB - OBJECTIVE: This study examined swallowing apnea duration (SAD) and respiratory phase patterns as a function of taste, tastes combined with barium, age, and genetic taste group. STUDY DESIGN: Prospective group design. SETTING: University medical center. SUBJECTS AND METHODS: Eighty healthy adult women were identified as nontasters and supertasters and equally comprised 2 age groups: 18 to 35 years (n = 40) and 60+ years (n = 40). The KayPentax Swallowing Signals Lab was used to acquire SAD and respiratory phase patterns via nasal cannula during randomized 5 mL swallows of water, 1.0 M sucrose (sweet), 1.0 M sodium chloride (salty), and 0.032 M caffeine (bitter) alone and mixed with barium. The SAD and respiratory patterns were analyzed in a linear mixed model and a binary logistic regression generalized estimating equation model, respectively. RESULTS: A significant main effect of age was found (P = .007). Older women demonstrated longer SAD than younger women. There were no significant effects of taste or genetic taste group on SAD. There was a significant interaction between barium and supertaster status; SAD was shorter in supertasters when barium was included. There were no significant differences in respiratory patterns between age groups, genetic taste groups, or among taste stimuli. CONCLUSION: Advanced age elicited longer SAD, a robust finding in repeated investigations from multiple laboratories. Main tastes did not affect SAD or respiratory phase patterns. Genetic taste group altered SAD when barium was combined with the taste. That is, taste + barium shortened SAD in supertasters. This finding may affect clinical management of dysphagia patients and warrants further investigation. PMID- 22677538 TI - The prostate cancer risk locus at 10q11 is associated with DNA repair capacity. AB - Genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) that mildly predict prostate cancer risk. These SNPs are local tagging markers for causal gene alterations. Consideration of candidate genes in the tagged regions would be facilitated by additional information on the particular pathomechanisms which contribute to the observed risk increase. In this study we test for an association of prostate cancer tagging SNPs with alterations in DNA repair capacity, a phenotype that is frequently involved in cancer predisposition. DNA repair capacity was assessed on blood lymphocytes from 128 healthy probands after ionizing irradiation. We used the micronucleus (MN) assay to determine the cellular DNA double-strand break repair capacity and flow cytometry to measure damage induced mitotic delay (MD). Probands were genotyped for a panel of 14 SNPs, each representing an independent prostate cancer risk locus previously identified by GWAS. Associations between germline variants and DNA repair capacity were found for the SNPs rs1512268 (8p21), rs6983267 (8q24) and rs10993994 (10q11). The most significant finding was an association of homozygous rs10993994 T-allele carriers with a lower MN frequency (p=0.0003) and also a decreased MD index (p=0.0353). Cells with prostate cancer risk alleles at rs10993994 seem to cope more efficiently with DNA double strand breaks (less MN) in a shorter time (decreased MD index). This intriguing finding imposes concern about the accuracy of repair, with respect to the cancer risk that is mediated by T genotypes. To date, MSMB (microseminoprotein beta) is favored as the causal gene at the 10q11 risk locus, since it was the first candidate gene known to be expressionally altered by rs10993994. Based on the present observation, candidate genes from the contexts of DNA repair and apoptosis may be more promising targets for expression studies with respect to the rs10993994 genotype. PMID- 22677539 TI - A combination of ascorbic acid and alpha-tocopherol or a combination of Mg and Zn are both able to reduce the adverse effects of lindane-poisoning on rat brain and liver. AB - The purpose of this study, carried out on male Wistar rats, was to evaluate the beneficial effects of supplementation with ascorbic acid (Vit C) and alpha tocopherol (Vit E) or with Mg and Zn upon lindane-induced damages in liver and brain. Under our experimental conditions, lindane poisoning (5mg/kg body weight per day for 3 days) resulted in (1) an increased level of plasma glucose, cholesterol and triglycerides, (2) an increased activity of LDH, ALP, AST, ALT, (3) an oxidative stress in liver and brain as revealed by an increased level of lipids peroxidation (TBARS) and a decrease of glutathione-peroxidase, superoxide dismutase and catalase activities in liver and brain. In conclusion, both Vit C+E or Mg+Zn treatments display beneficial effects upon oxidative stress induced by lindane treatment in liver and brain. PMID- 22677540 TI - The tetraethylammonium salt of monensic acid-An antidote for subacute cadmium intoxication: a study using an ICR mouse model. AB - In this study, the ability of the chelating agent monensic acid (administered as the tetraethylammonium salt) to reduce the cadmium (Cd) concentration in the kidneys, liver, heart, lungs, spleen and testes of Cd-intoxicated mice was investigated. Chelation therapy with the tetraethylammonium salt of monensic acid led to a significant decrease of the Cd concentration in all of the organs of the Cd-treated mice. This effect varied from 50% in the kidneys to 90% in the hearts of the sacrificed animals (compared to the Cd-treated controls). No redistribution of the toxic metal ions to the brain of the animals as a result of the detoxification with the chelating agent was observed. The detoxification of the animals with the antibiotic salt did not perturb the endogenous levels of copper (Cu) or zinc (Zn). The tetraethylammonium salt of monensic acid significantly ameliorated the Cd-induced total iron (Fe) depletion in the liver and spleen of Cd-treated mice. It also restored to control levels the values of transferrin-bound Fe and the total iron binding capacity (TIBC) of the plasma. These results imply that the tetraethylammonium salt of monensic acid could be an efficient antidote in cases of Cd-intoxication. PMID- 22677541 TI - Ontogenetic variations in Sr/Ca and Ba/Ca ratios of dental bioapatites from Bos taurus and Odocoileus virginianus. AB - Sr/Ca and Ba/Ca ratios of bone are commonly used as biochemical indicators of trophic level in modern and fossil mammals. Concerns over the effects of diagenesis on Sr/Ca and Ba/Ca ratios of bone led archaeologists and paleontologists to favor tooth enamel, which is less prone to alteration. Sr/Ca and Ba/Ca ratios of bone, enamel, and dentin from three farm-raised steers (Bos taurus) and five wild white-tailed deer (Odocoileus virginianus) from central Missouri were compared. Our results show that changes in diet, discrimination, and growth rate during ontogeny can lead to significant differences in Sr/Ca and Ba/Ca ratios of different bioapatite types as well as significant differences within the same bioapatite forming at different times. Early- and late-forming tooth enamel can have significant differences in Sr/Ca and Ba/Ca ratios equivalent to almost one full trophic step. Although differences between early- and late-forming dentin are typically not significant, dentin Sr/Ca and Ba/Ca ratios are significantly greater than enamel values. This difference in Sr/Ca or Ba/Ca ratios between enamel and dentin from the same tooth can be greater than one full trophic step. These results have profound implications for the use of dental bioapatites in trophic level reconstructions. They highlight the importance of consistency in bioapatite selection, tooth selection, and relative location of sampling within the enamel cap. Furthermore, this expected difference in Sr/Ca and Ba/Ca ratios could be used as another means of checking for diagenetic alteration in ancient samples. PMID- 22677542 TI - Effects of omeprazole consumption on serum levels of trace elements. AB - PROJECT: Omeprazole is one of the most frequently prescribed drugs in patients with gastroesophageal reflux disease (GERD). It increases the gastric pH and this in turn may change the intestinal absorption of trace elements. This study was conducted to assess the effects of omeprazole consumption on the serum level of trace elements. PROCEDURES: The studied subjects were selected from the list of patients referred to the gastroenterology department of 5 Azar hospital in Golestan province of Iran for whom omeprazole was prescribed by a gastroenterologist. Blood samples were obtained before (phase I) and after an eight-week period (phase II) of omeprazole consumption. Serum levels of trace elements were assessed by the photometric method. RESULTS: Sixty seven patients were recruited of whom, 35.82% were males. There was no significant difference in serum levels of Fe, P, Ca and Cu between phases I and II. Serum concentration of Zn was significantly lower in phase II than I (P=0.02). The proportion of male patients with low Zn levels was significantly higher in phase II (50%) than I (16.7%) (P=0.01). We found no significant difference in the proportion of female patients with low Zn levels between phase I (37.2%) and phase II (27.9%). CONCLUSIONS: We found no significant reduction in serum levels of Fe, P, Ca and Cu in phase II. However, our results showed that serum level of Zn was significantly lower after omeprazole consumption in males. So, nutritional supplement of Zn should be considered in male patients treated with omeprazole. PMID- 22677543 TI - Molecular analysis of Wilson patients: direct sequencing and MLPA analysis in the ATP7B gene and Atox1 and COMMD1 gene analysis. AB - ATP7B mutations result in Cu storage in the liver and brain in Wilson disease (WD). Atox1 and COMMD1 were found to interact with ATP7B and involved in copper transport in the hepatocyte. To understand the molecular etiology of WD, we analyzed ATP7B, Atox1 and COMMD1 genes. Direct sequencing of (i) ATP7B gene was performed in 112 WD patients to identify the spectrum of disease-causing mutations in the French population, (ii) Atox1 gene was performed to study the known polymorphism 5'UTR-99T>C in 78 WD patients with two ATP7B mutations and (iii) COMMD1 gene was performed to detect the nucleotide change c.492GAT>GAC. MLPA (Multiplex Ligation-dependent Probe Amplification) analysis was performed in WD patients presenting only one ATP7B mutation. Among our 112 WD unrelated patients, 83 different ATP7B gene mutations were identified, 27 of which were novel. Two ATP7B mutations were identified in 98 WD cases, and one mutation was identified in 14 cases. In two of these 14 WD patients, we identified the deletion of exon 4 of the ATP7B gene by MLPA technique. In 78 selected patients of the cohort with two mutations in ATP7B, we have examined genotype-phenotype correlation between the detected changes in Atox1 and COMMD1 genes, and the presentation of the WD patients. Based on the data of this study, no major role can be attributed to Atox1 and COMMD in the pathophysiology or clinical variation of WD. PMID- 22677544 TI - Chromatin in time and space. PMID- 22677545 TI - Cohesin: a guardian of genome integrity. AB - Ability to reproduce is one of the hallmark features of all life forms by which new organisms are produced from their progenitors. During this process each cell duplicates its genome and passes a copy of its genome to the daughter cells along with the cellular matrix. Unlike bacteria, in eukaryotes there is a definite time gap between when the genome is duplicated and when it is physically separated. Therefore, for precise halving of the duplicated genome into two, it is required that each pair of duplicated chromosomes, termed sister chromatids, should be paired together in a binary fashion from the moment they are generated. This pairing function between the duplicated genome is primarily provided by a multimeric protein complex, called cohesin. Thus, genome integrity largely depends on cohesin as it ensures faithful chromosome segregation by holding the sister chromatids glued together from S phase to anaphase. In this review, we have discussed the life cycle of cohesin during both mitotic and meiotic cell divisions including the structure and architecture of cohesin complex, relevance of cohesin associated proteins, mechanism of cohesin loading onto the chromatin, cohesion establishment and the mechanism of cohesin disassembly during anaphase to separate the sister chromatids. We have also focused on the role of posttranslational modifications in cohesin biology. For better understanding of the complexity of the cohesin regulatory network to the readers, we have presented an interactome profiling of cohesin core subunits in budding yeast during mitosis and meiosis. PMID- 22677546 TI - Inhibition of alpha-KG-dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors. AB - Two Krebs cycle genes, fumarate hydratase (FH) and succinate dehydrogenase (SDH), are mutated in a subset of human cancers, leading to accumulation of their substrates, fumarate and succinate, respectively. Here we demonstrate that fumarate and succinate are competitive inhibitors of multiple alpha-ketoglutarate (alpha-KG)-dependent dioxygenases, including histone demethylases, prolyl hydroxylases, collagen prolyl-4-hydroxylases, and the TET (ten-eleven translocation) family of 5-methlycytosine (5mC) hydroxylases. Knockdown of FH and SDH results in elevated intracellular levels of fumarate and succinate, respectively, which act as competitors of alpha-KG to broadly inhibit the activity of alpha-KG-dependent dioxygenases. In addition, ectopic expression of tumor-derived FH and SDH mutants inhibits histone demethylation and hydroxylation of 5mC. Our study suggests that tumor-derived FH and SDH mutations accumulate fumarate and succinate, leading to enzymatic inhibition of multiple alpha-KG dependent dioxygenases and consequent alterations of genome-wide histone and DNA methylation. These epigenetic alterations associated with mutations of FH and SDH likely contribute to tumorigenesis. PMID- 22677547 TI - Genetic and pharmacological disruption of the TEAD-YAP complex suppresses the oncogenic activity of YAP. AB - The Drosophila TEAD ortholog Scalloped is required for Yki-mediated overgrowth but is largely dispensable for normal tissue growth, suggesting that its mammalian counterpart may be exploited for selective inhibition of oncogenic growth driven by YAP hyperactivation. Here we test this hypothesis genetically and pharmacologically. We show that a dominant-negative TEAD molecule does not perturb normal liver growth but potently suppresses hepatomegaly/tumorigenesis resulting from YAP overexpression or Neurofibromin 2 (NF2)/Merlin inactivation. We further identify verteporfin as a small molecule that inhibits TEAD-YAP association and YAP-induced liver overgrowth. These findings provide proof of principle that inhibiting TEAD-YAP interactions is a pharmacologically viable strategy against the YAP oncoprotein. PMID- 22677549 TI - Knocking out podocyte rho GTPases: and the winner is... PMID- 22677548 TI - Scube/You activity mediates release of dually lipid-modified Hedgehog signal in soluble form. AB - Owing to their covalent modification by cholesterol and palmitate, Hedgehog (Hh) signaling proteins are localized predominantly to the plasma membrane of expressing cells. Yet Hh proteins are also capable of mobilizing to and eliciting direct responses from distant cells. The zebrafish you gene, identified genetically >15 years ago, was more recently shown to encode a secreted glycoprotein that acts cell-nonautonomously in the Hh signaling pathway by an unknown mechanism. We investigated the function of the protein encoded by murine Scube2, an ortholog of you, and found that it mediates release in soluble form of the mature, cholesterol- and palmitate-modified Sonic hedgehog protein signal (ShhNp) when added to cultured cells or purified detergent-resistant membrane microdomains containing ShhNp. The efficiency of Scube2-mediated release of ShhNp is enhanced by the palmitate adduct of ShhNp and by coexpression in ShhNp producing cells of mDispatchedA (mDispA), a transporter-like protein with a previously defined role in the release of lipid-modified Hh signals. The structural determinants of Scube2 required for its activity in cultured cell assays match those required for rescue of you mutant zebrafish embryos, and we thus conclude that the role of Scube/You proteins in Hh signaling in vivo is to facilitate the release and mobilization of Hh proteins for distant action. PMID- 22677550 TI - Pathology after eculizumab in dense deposit disease and C3 GN. AB - Eculizumab might benefit C3 glomerulopathies mediated by dysregulation of the alternative complement pathway. Here, we report renal biopsy findings before and after eculizumab therapy in three patients with dense deposit disease and two with C3 GN. All pretreatment biopsies had glomerular and tubular basement membrane deposits that stained exclusively for C3 without significant Ig. After 1 year of therapy, there was reduction in active glomerular proliferation and neutrophil infiltration in three of five patients, consistent with effective C5 blockade, which prevents production of chemotactin C5a. One individual with mild mesangial disease had no significant change in activity or chronicity. One patient exhibited persistent activity and worsening chronicity despite therapy. Immunofluorescence showed no significant reduction in C3 or C5b-9, and electron microscopy revealed persistent deposits in all cases, suggesting a long t(1/2) of C5b-9 in extracellular matrix. Normal renal biopsies stained positive for C5b-9 in glomeruli, tubular basement membranes, and vessel walls, albeit at lower intensity than in C3 glomerulopathy. This indication of physiologic levels of C5b 9 activation in normal kidney potentially explains the localization of deposits in patients with dysregulation of the alternative complement pathway. All post treatment biopsies showed de novo monoclonal staining for IgG-kappa in the same distribution as C3 and C5b-9, mimicking monoclonal Ig deposition disease (MIDD). Staining of the gamma heavy chain was restricted to the IgG2 and IgG4 subclasses, suggesting the binding of monoclonal eculizumab to C5 in renal tissues. The long term effects of this apparent drug-tissue interaction are unknown. PMID- 22677552 TI - Mechanisms of renal disease in beta-thalassemia. AB - Although advances in the care of patients with beta-thalassemia translate into better patient survival, this success has allowed previously unrecognized complications to emerge, including several renal abnormalities. Clinical studies continue to show that mild tubular dysfunction and abnormalities in GFR are common in patients with beta-thalassemia. Chronic anemia and iron overload are believed to lie behind these abnormalities. Nonprogressive increases in levels of serum creatinine have also been observed after exposure to some iron chelators. Longitudinal studies are needed to understand the true burden of renal dysfunction in patients with beta-thalassemia. PMID- 22677551 TI - Histones from dying renal cells aggravate kidney injury via TLR2 and TLR4. AB - In AKI, dying renal cells release intracellular molecules that stimulate immune cells to secrete proinflammatory cytokines, which trigger leukocyte recruitment and renal inflammation. Whether the release of histones, specifically, from dying cells contributes to the inflammation of AKI is unknown. In this study, we found that dying tubular epithelial cells released histones into the extracellular space, which directly interacted with Toll-like receptor (TLR)-2 (TLR2) and TLR4 to induce MyD88, NF-kappaB, and mitogen activated protein kinase signaling. Extracellular histones also had directly toxic effects on renal endothelial cells and tubular epithelial cells in vitro. In addition, direct injection of histones into the renal arteries of mice demonstrated that histones induce leukocyte recruitment, microvascular vascular leakage, renal inflammation, and structural features of AKI in a TLR2/TLR4-dependent manner. Antihistone IgG, which neutralizes the immunostimulatory effects of histones, suppressed intrarenal inflammation, neutrophil infiltration, and tubular cell necrosis and improved excretory renal function. In summary, the release of histones from dying cells aggravates AKI via both its direct toxicity to renal cells and its proinflammatory effects. Because the induction of proinflammatory cytokines in dendritic cells requires TLR2 and TLR4, these results support the concept that renal damage triggers an innate immune response, which contributes to the pathogenesis of AKI. PMID- 22677553 TI - IL-2/IL-2Ab complexes induce regulatory T cell expansion and protect against proteinuric CKD. AB - Regulatory T cells (Tregs) help protect against autoimmune renal injury. The use of agonist antibodies and antibody/cytokine combinations to expand Tregs in vivo may have therapeutic potential for renal disease. Here, we investigated the effects of administering IL-2/IL-2Ab complexes in mice with adriamycin nephropathy, a model of proteinuric kidney disease that resembles human focal segmental glomerulosclerosis. Injecting IL-2/IL-2Ab complexes before or, to a lesser extent, after induction of disease promoted expansion of Tregs. Furthermore, administration of this complex was renoprotective, evidenced by improved renal function, maintenance of body weight, less histologic injury, and reduced inflammation. IL-2/IL-2Ab reduced serum IL-6 and renal expression of IL-6 and IL-17 but enhanced expression of IL-10 and Foxp3 in the spleen. In vitro, the addition of IL-2/IL-2Ab complexes induced rapid STAT-5 phosphorylation in CD4 T cells. In summary, these data suggest that inducing the expansion of Tregs by administering IL-2/IL-2Ab complexes is a possible strategy to treat renal disease. PMID- 22677554 TI - Reimbursement of dialysis: a comparison of seven countries. AB - Reimbursement for chronic dialysis consumes a substantial portion of healthcare costs for a relatively small proportion of the total population. Each country has a unique reimbursement system that attempts to control rising costs. Thus, comparing the reimbursement systems between countries might be helpful to find solutions to minimize costs to society without jeopardizing quality of treatment and outcomes. We conducted a survey of seven countries to compare crude reimbursement for various dialysis modalities and evaluated additional factors, such as inclusion of drugs or physician payments in the reimbursement package, adjustment in rates for specific patient subgroups, and pay for performance therapeutic thresholds. The comparison examines the United States, the province of Ontario in Canada, and five European countries (Belgium, France, Germany, The Netherlands, and the United Kingdom). Important differences between countries exist, resulting in as much as a 3.3-fold difference between highest and lowest reimbursement rates for chronic hemodialysis. Differences persist even when our data were adjusted for per capita gross domestic product. Reimbursement for peritoneal dialysis is lower in most countries except Germany and the United States. The United Kingdom is the only country that has implemented an incentive if patients use an arteriovenous fistula. Although home hemodialysis (prolonged or daily dialysis) allows greater flexibility and better patient outcomes, reimbursement is only incentivized in The Netherlands. Unfortunately, it is not yet clear that such differences save money or improve quality of care. Future research should focus on directly testing both outcomes. PMID- 22677555 TI - Sodium chloride intake: is lower always better? AB - Current treatment of kidney disease is not completely satisfactory, particularly when initiated in the late stages of renal progression. There is an urgent need for additional interventions, especially reduction of salt intake, which is rather high in the Western world. In this commentary we provide a critical assessment of post hoc analyses of recent interventional and observational studies on the effect of salt intake on renal and cardiovascular outcomes. To evaluate the mechanisms and safety of reduced salt intake, studies specifically designed to assess salt intake as an endpoint are needed. This approach will have implications for health care policies and labeling of the salt content of purchased foods. PMID- 22677556 TI - The increasing complexity of the intratubular Renin-Angiotensin system. PMID- 22677558 TI - Renal nerves and CKD: is renal denervation the answer? PMID- 22677557 TI - Tissue plasminogen activator activates NF-kappaB through a pathway involving annexin A2/CD11b and integrin-linked kinase. AB - NF-kappaB activation is central to the initiation and progression of inflammation, which contributes to the pathogenesis of CKD. Tissue plasminogen activator (tPA) modulates the NF-kappaB pathway, but the underlying mechanism remains unknown. We investigated the role of tPA signaling in macrophage NF kappaB activation and found that tPA activated NF-kappaB in a time- and dose dependent manner. tPA also induced the expression of the NF-kappaB-dependent chemokines IP-10 and MIP-1alpha. The protease-independent action of tPA required its membrane receptor, annexin A2. tPA induced the aggregation and interaction of annexin A2 with integrin CD11b, and ablation of CD11b or administration of anti CD11b neutralizing antibody abolished the effect of tPA. Knockdown of the downstream effector of CD11b, integrin-linked kinase, or disruption of its engagement with CD11b also blocked tPA-induced NF-kappaB signaling. In vivo, tPA knockout mice had reduced NF-kappaB signaling, fewer renal macrophages, and less collagen deposition than their counterparts. Taken together, these data suggest that tPA activates the NF-kappaB pathway in macrophages through a signaling pathway involving annexin A2/CD11b-mediated integrin-linked kinase. PMID- 22677560 TI - On Mesopithecus habitat: Insights from late Miocene fossil vertebrate localities of Bulgaria. AB - The aim of this study is to describe the environments where the cercopithecid Mesopithecus was found during latest Miocene in Europe. For this purpose, we investigate the paleoecology of the herbivorous ungulate mesofauna of three very rich late Miocene fossil localities from southwestern Bulgaria: Hadjidimovo, Kalimantsi and Strumyani. While Mesopithecus has been found in the two first localities, no primate remains have yet been identified in Strumyani. Comparison between localities with and without primates using the herbivore mesofauna allows the cross-corroboration of paleoenvironmental conditions where this primate did and did not live. A multi-parameter statistical approach involving 117 equid and 345 bovid fossil dental and postcranial (phalanges, metapodia, astragali) remains from these three localities provides species to generic-level diet and locomotor habit information in order to characterize the environment in which Mesopithecus evolved. The analysis of dental mesowear indicates that the bovids were mainly mixed feeders, while coeval equids were more engaged in grazing. Meanwhile, postcranial remains show that the ungulate species from Hadjidimovo and Kalimantsi evolved in dry environments with a continuum of habitats ranging from slightly wooded areas to relatively open landscapes, whereas the Mesopithecus free Strumyani locality was in comparison reflecting a rather contrasted mosaic of environments with predominant open and some more closed and wet areas. Environments in which Mesopithecus is known during the late Miocene were not contrasted landscapes combining open grassy areas and dense forested patches, but instead rather restricted to slightly wooded and homogeneous landscapes including a developed grassy herbaceous layer. PMID- 22677559 TI - c-Met and NF-kappaB-dependent overexpression of Wnt7a and -7b and Pax2 promotes cystogenesis in polycystic kidney disease. AB - The mechanisms of cystogenesis in autosomal dominant polycystic kidney disease (ADPKD) are not fully understood. Hyperactivation of the tyrosine kinase c-Met contributes to cyst formation, but we do not know the downstream mediators. Here, we found that hyperactivated c-Met led to increased NF-kappaB signaling, which in turn, drove de novo expression of Wnt7a and overexpression of Wnt7b in Pkd1(-/-) mouse kidneys. Hyperactivated Wnt signaling increased expression of the transcription factor Pax2 in the cells lining cysts. Furthermore, blocking Wnt signaling with DKK1 decreased cyst formation in an organ culture model of ADPKD. In summary, these results suggest that the c-Met/NF-kappaB/Wnt/Pax2 signaling transduction axis may provide pharmacological targets for the treatment of ADPKD. PMID- 22677562 TI - The role of nutrition and effects on the cytokine milieu in allogeneic hematopoietic stem cell transplantation. AB - Nutritional deficiency is very common after allogeneic stem cell transplantation (HSCT) despite careful assessment and nutritional supplementation (total parenteral or oral nutrition). The importance of nutrition in the immune system has been well defined during the past several years, as it has modulatory effects on the immune system. One of the most frequent questions in nutrition is whether nutritionally at-risk hosts have a defect in their immune system and whether such defects can be corrected by nutritional supplementation. Addressing nutritional supplementation starting from early post-transplantation might decrease the risk of infectious complication and GVHD after HSCT via the immunomodulatory role of a variety of nutrients and supplements. Given the well-established link between nutrition and immunomodulation, we hypothesize that timely nutritional supplementation can potentially play a direct or indirect role in decreasing non relapse morbidity and mortality after HSCT. In this article, we discuss the possible link between nutritional deficiency and its effects on the cytokine milieu after HSCT. PMID- 22677561 TI - Extracts of Larix Leptolepis effectively augments the generation of tumor antigen specific cytotoxic T lymphocytes via activation of dendritic cells in TLR-2 and TLR-4-dependent manner. AB - Type-1 immunity plays a crucial role in host defense against various tumors and infectious diseases. Here, we first demonstrated that extract of Larix Leptolepis (ELL), one of the most popular timbers at Hokkaido area in Japan, strongly activated Type-1 immunity. ELL induced production of Type-1 cytokines such as IL 12 and TNF-alpha from bone marrow-derived dendritic cells (BMDCs) in TLR2- and TLR4-dependent manner and remarkably up-regulated the expression of MHC and co stimulatory molecules. In addition, antigen-specific CTLs were significantly augmented by the combined administration of ELL, antigen and BMDCs. Finally, we revealed that combination therapy using ELL, antigen and BMDCs significantly inhibited the growth of established tumor in mouse model. Thus, these findings suggested that ELL would be a novel adjuvant for inducing an activation of Type-1 dependent immunity including activation of BMDCs and induction of tumor-specific CTLs, which is applicable to the therapy of cancer and infectious diseases. PMID- 22677563 TI - Electrically-responsive anti-adherent hydrogels for photodynamic antimicrobial chemotherapy. AB - The loading of the photosensitisers meso-Tetra (N-methyl-4-pyridyl) porphine tetra tosylate (TMP), methylene blue (MB) and TMP with sodium dodecyl sulphate (SDS) into and release from hydrogels composed of the polyelectrolyte poly(methyl vinyl ether-co-maleic acid) crosslinked in a 2:1 ratio with PEG 10,000 were investigated as a potential rapid photodynamic antimicrobial chemotherapy (PACT) treatment for infected wounds using iontophoresis as a novel delivery method. Photosensitiser uptake was very high; (% TMP uptake; 95.53-96.72%) (% MB uptake; 90.58-93.26%) and was PMVE/MA concentration independent, whilst SDS severely limited TMP uptake (5.93-8.75%). Hydrogel hardness, compressibility and adhesiveness on the dermal surface of neonate porcine skin increased with PMVE/MA concentration and were significantly increased with SDS. The ionic conductivities of the hydrogels increased with PMVE/MA concentration. Drug release was PMVE/MA concentration independent, except for drug release under iontophoteric conditions for MB and TMP (without SDS). In just 15 min, the mean% drug concentrations released of TMP, TMP (with SDS) and MB using an electric current ranged from 22.30 to 64.72 MUg ml(-1), 6.37-4.59 MUg ml(-1) and 11.73-36.57 MUg ml(-1) respectively. These concentrations were in excess of those required to induce complete kill of clinical strains of meticillin-resistant Staphylococcus aureus and Burkholderia cepacia. Thus these results support our contention that the iontophoteric delivery of TMP and MB using anti-adherent, electrically responsive, PEG-crosslinked PMVE/MA hydrogels are a potential option in the rapid PACT treatment of infected wounds. PMID- 22677564 TI - Assessment of amsacrine binding with DNA using UV-visible, circular dichroism and Raman spectroscopic techniques. AB - Proper understanding of the mechanism of binding of drugs to their targets in cell is a fundamental requirement to develop new drug therapy regimen. Amsacrine is a rationally designed anticancer drug, used to treat leukemia and lymphoma. Binding with cellular DNA is a crucial step in its mechanism of cytotoxicity. Despite numerous studies, DNA binding properties of amsacrine are poorly understood. Its reversible binding with DNA does not permit X-ray crystallography or NMR spectroscopic evaluation of amsacrine-DNA complexes. In the present work, interaction of amsacrine with calf thymus DNA is investigated at physiological conditions. UV-visible, FT-Raman and circular dichroism spectroscopic techniques were employed to determine the binding mode, binding constant, sequence specificity and conformational effects of amsacrine binding to native calf thymus DNA. Our results illustrate that amsacrine interacts with DNA by and large through intercalation between base pairs. Binding constant of the amsacrine-DNA complex was found to be K=1.2+/-0.1*10(4) M(-1) which is indicative of moderate type of binding of amsacrine to DNA. Raman spectroscopic results suggest that amsacrine has a binding preference of intercalation between AT base pairs of DNA. Minor groove binding is also observed in amsacrine-DNA complexes. These results are in good agreement with in silico investigation of amsacrine binding to DNA and thus provide detailed insight into DNA binding properties of amsacrine, which could ultimately, renders its cytotoxic efficacy. PMID- 22677565 TI - Risk of autism spectrum disorders in low birth weight and small for gestational age infants. AB - OBJECTIVE: To examine the relationship between birth weight, gestational age, small for gestational age (SGA), and 3 of the most common autism spectrum disorder (ASD) subtypes. STUDY DESIGN: In this population-based case-control study conducted in Finland, 4713 cases born between 1987 and 2005 with International Classification of Diseases-diagnoses of childhood autism, Asperger syndrome, or pervasive developmental disorder (PDD), were ascertained from the Finnish Hospital Discharge Register. Four controls, individually matched on sex, date of birth, and place of birth, were selected from the Finnish Medical Birth Register for each case. Conditional logistic regression models were used to assess whether birth weight and gestational age information predicted ASD after controlling for maternal age, parity, smoking during pregnancy, and psychiatric history, as well as for infant's major congenital anomalies. RESULTS: Very low (<1500 g) and moderately low (<2500 g) birth weight, very low gestational age (less than 32 weeks), and SGA increased risk of childhood autism (adjusted OR 3.05, 95% CI 1.4-6.5; 1.57, 1.1-2.3; 2.51, 1.3-5.0; and 1.72, 1.1-2.6, respectively). Very low and moderately low birth weight, very low gestational age, and SGA were also associated with increase in PDD risk (OR 3.44, 95% CI 1.9 6.3; 1.81, 1.4-2.4; 2.46, 1.4-2.3; and 2.24, 1.7-3.0, respectively). No associations were found between the perinatal characteristics and Asperger syndrome. The increased risks persisted after controlling for selected potential confounders. CONCLUSIONS: The finding that low birth weight, prematurity, and SGA were related to childhood autism and PDD but not to Asperger syndrome suggests that prenatal factors related to these exposures may differ for these ASD subtypes, which may have preventive implications. PMID- 22677566 TI - Vitamin D status is linked to biomarkers of oxidative stress, inflammation, and endothelial activation in obese children. AB - OBJECTIVE: To examine vitamin D, parathyroid hormone, and serum calcium phosphorus levels relationships to biomarkers of oxidative/nitrosative stress, inflammation, and endothelial activation, potential contributors for vascular complications in obese children. STUDY DESIGN: Cross-sectional clinical study of 66 obese Caucasian children aged 7 to 14 years. Cardiovascular risk factors were assessed. Malondialdehyde and myeloperoxidase as measures of oxidative stress, and plasma nitrite+nitrate, urinary nitrate, and 3-nitrotyrosine as markers of nitrosative stress were measured. Adipocytokines, inflammatory molecules (high sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-alpha), endothelial activation molecules (soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule 1 [sVCAM-1]), E-selectin, and vascular endothelial growth factor were also investigated. Serum 25-hydroxy cholecalciferol [25(OH)D], intact parathormone, and calcium-phosphorus levels were determined in these children and in a comparison group of 39 non-obese children. RESULTS: Obese children had a significantly lower 25(OH)D level (P = .002) and a higher intact parathormone (P = .011) than non-obese children. Phosphorus and the calcium-phosphorus product were also significantly higher (P < .0001). Insufficient serum concentrations of 25(OH)D (<20 ng/mL) were detected in 5% of normal children and in 30% of the obese children. In the obese children with vitamin D insufficiency, malondialdehyde, myeloperoxidase, 3-nitrotyrosine, interleukin-6, and sVCAM-1 were substantially elevated. A partial correlation analysis showed an inverse relationship of 25(OH)D levels with 3-nitrotyrosine (r = -0.424, P = .001), and sVCAM-1 (r = -0.272, P = .032). CONCLUSIONS: Insufficient 25(OH)D levels were detected in severely obese children with increased markers of oxidative/nitrosative stress, inflammation, and endothelial activation. PMID- 22677567 TI - Thermal imaging to assess age-related changes of skin temperature within the supraclavicular region co-locating with brown adipose tissue in healthy children. AB - OBJECTIVE: To establish the feasibility of infrared thermal imaging as a reproducible, noninvasive method for assessing changes in skin temperature within the supraclavicular region in vivo. STUDY DESIGN: Thermal imaging was used to assess the effect of a standard cool challenge (by placement of the participant's feet or hand in water at 20 degrees C) on the temperature of the supraclavicular region in healthy volunteer participants of normal body mass index in 3 age groups, 3-8, 13-18, and 35-58 years of age. RESULTS: We demonstrated a highly localized increase in temperature within the supraclavicular region together with a significant age-related decline under both baseline and stimulated conditions. CONCLUSION: Thermogenesis within the supraclavicular region can be readily quantified by thermal imaging. This noninvasive imaging technique now has the potential to be used to assess brown adipose tissue function alone, or in combination with other techniques, in order to determine the roles of thermogenesis in energy balance and, therefore, obesity prevention. PMID- 22677569 TI - Determining the influence of muscle operating length on muscle performance during frog swimming using a bio-robotic model. AB - Frogs are capable of impressive feats of jumping and swimming. Recent work has shown that anuran hind limb muscles can operate at lengths longer than the 'optimal length'. To address the implications of muscle operating length on muscle power output and swimming mechanics, we built a robotic frog hind limb model based upon Xenopus laevis. The model simulated the force-length and force velocity properties of vertebrate muscle, within the skeletal environment. We tested three muscle starting lengths, representing long, optimal and short starting lengths. Increasing starting length increased maximum muscle power output by 27% from 98.1 W kg(-1) when muscle begins shortening from the optimal length, to 125.1 W kg(-1) when the muscle begins at longer initial lengths. Therefore, longer starting lengths generated greater hydrodynamic force for extended durations, enabling faster swimming speeds of the robotic frog. These swimming speeds increased from 0.15 m s(-1) at short initial muscle lengths, to 0.39 m s(-1) for the longest initial lengths. Longer starting lengths were able to increase power as the muscle's force-length curve was better synchronized with the muscle's activation profile. We further dissected the underlying components of muscle force, separating force-length versus force-velocity effects, showing a transition from force-length limitations to force-velocity limitations as starting length increased. PMID- 22677568 TI - A randomized, prospective, comparison study of a mixture of acacia fiber, psyllium fiber, and fructose vs polyethylene glycol 3350 with electrolytes for the treatment of chronic functional constipation in childhood. AB - OBJECTIVES: To compare the effectiveness of a mixture of acacia fiber, psyllium fiber, and fructose (AFPFF) with polyethylene glycol 3350 combined with electrolytes (PEG+E) in the treatment of children with chronic functional constipation (CFC); and to evaluate the safety and effectiveness of AFPFF in the treatment of children with CFC. STUDY DESIGN: This was a randomized, open label, prospective, controlled, parallel-group study involving 100 children (M/F: 38/62; mean age +/- SD: 6.5 +/- 2.7 years) who were diagnosed with CFC according to the Rome III Criteria. Children were randomly divided into 2 groups: 50 children received AFPFF (16.8 g daily) and 50 children received PEG+E (0.5 g/kg daily) for 8 weeks. Primary outcome measures were frequency of bowel movements, stool consistency, fecal incontinence, and improvement of other associated gastrointestinal symptoms. Safety was assessed with evaluation of clinical adverse effects and growth measurements. RESULTS: Compliance rates were 72% for AFPFF and 96% for PEG+E. A significant improvement of constipation was seen in both groups. After 8 weeks, 77.8% of children treated with AFPFF and 83% of children treated with PEG+E had improved (P = .788). Neither PEG+E nor AFPFF caused any clinically significant side effects during the entire course of the study period. CONCLUSIONS: In this randomized study, we did not find any significant difference between the efficacy of AFPFF and PEG+E in the treatment of children with CFC. Both medications were proved to be safe for CFC treatment, but PEG+E was better accepted by children. PMID- 22677570 TI - Electrophysiological study of face inversion effects in Williams syndrome. AB - OBJECTIVE: In order to evaluate whether face perception is intact or not in Williams syndrome (WS), the face inversion effects (FIE) in the event-related potential (ERP) or magnetoencephalography (MEG) were investigated in three teenaged patients with WS. METHODS: Responses to the inverted faces and upright faces were compared using MEG for one 13year old girl with WS (subject A) and ERP for boys with WS at 16 and 14years of age (subjects B and C, respectively). RESULTS: Although age-matched control children showed FIE in both MEG and ERP studies, two subjects (A and B) with WS showed no FIE at all. The neurophysiological data of ERP in subject B was significantly different from those of the age-matched controls. On the other hand, a boy with WS (subject C) showed typical FIE in the same manner as the age-matched controls. CONCLUSIONS: The difference between those with or without FIE was not explained merely by the chronological age, a simple delay in mental age or in the ability to discriminate among upright faces. The absence of FIE may be related to the severity of a deficit in the dorsal pathway function that is characteristic to the syndrome. PMID- 22677571 TI - Neuropathology of leukoencephalopathy with brainstem and spinal cord involvement and high lactate caused by a homozygous mutation of DARS2. AB - We diagnosed three siblings from consanguineous east Asian parents with leukoencephalopathy with brainstem and spinal cord involvement and high lactate (LBSL) from characteristic MRI, MRS findings and a homozygous mutation in the DARS2 gene. The neurological symptoms of the three patients consisted of psychomotor developmental delay, cerebellar ataxia since infancy, spasticity in the initial phase and peripheral neuropathy in later stages. Their mental development was delayed, but did not deteriorate. MRI signal abnormalities included the same abnormalities reported previously but tended to be more extensive. Signal abnormalities in the cerebral and cerebellar white matter were homogeneous and confluent from early stages. In addition, other tract such as the central tegmental tract was involved. Furthermore, an atrophic change in the cerebral white matter was observed on follow-up in one case. Two of the patients were autopsied and neuropathological findings revealed characteristic vacuolar changes in the white matter of the cerebrum, cerebellum and the nerve tracts of the brain stem and spinal cord. The central myelin sheath showed intralamellar splitting by electron microscopy. These findings were consistent to a spongy degeneration in the diffuse white matter of the brain, or spongiform leukoencephalopathy. In addition, peripheral nerves showed both axonal degeneration and abnormal myelin structures. We discussed the relationship between deficits in mitochondrial aspartyl-tRNA synthetase activity and the neuropathology observed. PMID- 22677572 TI - A systematic review of neoadjuvant and adjuvant chemotherapy for muscle-invasive bladder cancer. AB - CONTEXT: Muscle-invasive bladder cancer (MIBC) is a disease with a pattern of predominantly distant and early recurrences. Neoadjuvant cisplatin-based combination chemotherapy has demonstrated improved outcomes for MIBC. OBJECTIVE: To review the data supporting perioperative chemotherapy and emerging regimens for MIBC. EVIDENCE ACQUISITION: Medline databases were searched for original articles published before April 1, 2012, with the search terms bladder cancer, urothelial cancer, radical cystectomy, neoadjuvant chemotherapy, and adjuvant chemotherapy. Proceedings from the last 5 yr of major conferences were also searched. Novel and promising drugs that have reached clinical trial evaluation were included. EVIDENCE SYNTHESIS: The major findings are addressed in an evidence-based fashion. Prospective trials and important preclinical data were analyzed. CONCLUSIONS: Cisplatin-based neoadjuvant combination chemotherapy is an established standard, improving overall survival in MIBC. Pathologic complete response appears to be an intermediate surrogate for survival, but this finding requires further validation. Definitive data to support adjuvant chemotherapy do not exist, and there are no data to support perioperative therapy in cisplatin ineligible patients. Utilization of neoadjuvant cisplatin is low, attributable in part to patient/physician choice and the advanced age of patients, who often have multiple comorbidities including renal and/or cardiac dysfunction. Trials are using the neoadjuvant paradigm to detect incremental pathologic response to chemobiologic regimens and brief neoadjuvant single-agent therapy to screen for the biologic activity of agents. PMID- 22677573 TI - Mucinous cystadenocarcinoma of the appendix mimics acute appendicitis. PMID- 22677574 TI - Factors associated with diagnosis of obscure gastrointestinal bleeding by video capsule enteroscopy. AB - BACKGROUND & AIMS: Capsule enteroscopy (CE) is the best noninvasive tool to explore the entire small bowel of patients with obscure gastrointestinal bleeding (OGIB); it has a diagnostic yield of 40%-80%. However, little is known about the factors associated with a diagnosis of OGIB by CE. METHODS: We analyzed data from 911 consecutive patients who underwent CE for OGIB from January 2004 to January 2010. Results from upper and lower gastrointestinal endoscopy examinations were negative in all patients. CE findings were recorded. Features of patients that were associated with diagnosis of OGIB by CE were identified by using logistic regression. RESULTS: Based on CE, 509 patients (56%) had a confirmed lesion responsible for the OGIB: 203 had disease of the small bowel (22%), 88 had ulcerations (10%), 70 had tumors (8%), 24 had varices (2%), 6 had diverticula (0.5%), and 118 had what appeared to be bleeding lesions of the esophagus or stomach (10.6%) or colon (2%). Factors independently associated with a diagnosis of OGIB by CE were age >60 years (odds ratio [OR], 1.2), male sex, history of overt bleeding (OR, 3.8), and current hospitalization (OR, 1.4). Women were less likely to be diagnosed with OGIB by CE (OR, 0.7). CONCLUSIONS: A history of overt bleeding is the factor most strongly associated with a diagnosis of OGIB by CE. Male sex, age >60 years, and inpatient status were also independent predictors of positive diagnosis by CE. PMID- 22677575 TI - Tissue yield and diagnostic efficacy of fluoroscopic and cholangioscopic techniques to assess indeterminate biliary strictures. AB - BACKGROUND & AIMS: Evaluation of indeterminate biliary strictures typically involves collection and analysis of tissue or cells. Single-operator, peroral, cholangioscopic techniques have been developed that allow for a biopsy sample to be obtained from a specific area of the visualized stricture. We investigated whether standard fluoroscopic-guided and cholangioscopic-directed (SpyGlass Direct Visualization System; Boston Scientific, Natick, MA) biopsy collection provide adequate tissue for histologic assessment. METHODS: We examined 110 consecutive bile duct specimens collected from 89 patients with indeterminate biliary strictures at a single institution using fluoroscopy or cholangioscopy (from October 2007 to March 2010). Because of the small nature of the intraductal biopsy fragments, special procedures were followed in the pathology laboratory to maximize the amount of tissue for histopathology analysis. RESULTS: Only 4 specimens (3.6%) had insufficient material for a diagnosis. More tissue was obtained from standard fluoroscopic-guided than cholangioscopic-directed biopsies (more biopsy fragments, P = .018; larger total biopsy size, P = .001). Fluoroscopy-guided biopsies assessed indeterminate biliary strictures with 76% sensitivity and 88% accuracy; these values were 57% and 78%, respectively, for cholangioscopic-directed biopsies. Each procedure had 100% specificity. CONCLUSIONS: Analysis of bile duct biopsies is important in management of patients with indeterminate biliary strictures. Use of a special handling protocol for these small biopsies could reduce the number of cases with insufficient material for diagnosis. Increasing the sample size (either by using larger biopsy forceps or obtaining more biopsy bites) could improve the sensitivity of the SpyGlass technique. As endoscopists and pathologists gain more experience in collecting and handling small biopsies, the diagnostic efficacy of intraductal biopsies will continue to improve. PMID- 22677576 TI - Muscle trigger points, pressure pain threshold, and cervical range of motion in patients with high level of disability related to acute whiplash injury. AB - STUDY DESIGN: Cross sectional cohort study. OBJECTIVE: To analyze the differences in the prevalence of trigger points (TrPs) between patients with acute whiplash associated disorders (WADs) and healthy controls, and to determine if widespread pressure hypersensitivity and reduced cervical range of motion are related to the presence of TrPs in patients with acute WADs. BACKGROUND: The relationship between active TrPs and central sensitization is not well understood in patients with acute WADs. METHODS: Twenty individuals with a high level of disability related to acute WAD and 20 age- and sex-matched controls participated in the study. TrPs in the temporalis, masseter, upper trapezius, levator scapulae, sternocleidomastoid, suboccipital, and scalene muscles were examined. TrPs are defined as hypersensitive spots in a palpable taut band, producing a local twitch response and referred pain when palpated. Pressure pain threshold (PPT) was assessed bilaterally over the C5-6 zygapophyseal joints, second metacarpal, and tibialis anterior muscle. Active cervical range of motion, neck pain, and self rated disability using the Neck Disability Index were also assessed. RESULTS: The mean +/- SD number of TrPs for the patients with acute WAD was 7.3 +/- 2.8 (3.4 +/- 2.7 were latent TrPs; 3.9 +/- 2.5 were active TrPs). In comparison, healthy controls had 1.7 +/- 2.2 latent and no active TrPs (P<0.01). In patients with acute WAD, the most prevalent sites for active TrPs were the levator scapulae and upper trapezius muscles. The number of active TrPs increased with higher neck pain intensity (P<0.001) and a higher number of days since the accident (P=.003). Patients had significantly lower PPTs in all tested locations and less active cervical range of motion than controls (P<.001). In the patient group, there were significant negative correlations between the number of active TrPs and PPT over the C5-C6 joints and cervical range of motion in flexion, extension, and rotation in both directions: the greater the number of active TrPs, the lower the bilateral PPT over the neck and the greater the cervical range of motion limitation. CONCLUSIONS: The local and referred pain elicited from active TrPs reproduced neck and shoulder pain patterns in individuals with acute WADs with higher levels of disability. Patients with acute WADs exhibited widespread pressure hypersensitivity and reduced cervical mobility. The number of active TrPs was related to higher neck pain intensity, the number of days since the accident, higher pressure pain hypersensitivity over the cervical spine, and reduced active cervical range of motion. PMID- 22677577 TI - Nod-like receptors in the control of intestinal inflammation. AB - The Nod-like receptor (NLR) family of intracellular pattern recognition molecules plays critical roles in the control of inflammation through the modulation of different signalling pathways, including those dependent on NF-kappaB and caspase 1-mediated cleavage of interleukin (IL)-1beta and IL-18. A number of NLRs or NLR associated proteins have been genetically associated with susceptibility to inflammatory bowel disease (IBD), either Crohn's disease or ulcerative colitis. Accordingly, recent studies have examined the role of NLR proteins in chemical induced or bacteria-induced murine models of colitis. In this review, we will discuss the genetic associations of NLRs with IBD and the research using NLR deficient mice in different colitis models. PMID- 22677578 TI - Quality improvement requirement. PMID- 22677579 TI - A new training model for adult circumcision. AB - BACKGROUND: Adult circumcision is an extremely common surgical operation. As such, we developed a simple model to teach junior doctors the various techniques of circumcision in a safe, reliable, and realistic manner. MATERIALS AND METHODS: A commonly available simulated model penis (Pharmabotics, Limited, Winchester, United Kingdom) is used, which is then covered with a 30-mm diameter, 400-mm long, double-layered simulated bowel (Limbs & Things, Bristol, United Kingdom). The 2 layers of the prepuce are simulated by folding the simulated bowel on itself. The model has been officially adopted in the UroEmerge hands-on practical skills course and all participants were asked to provide feedback about their experience on a scale from 1 to 10 (1 = extremely unsatisfied and 10 = excellent). RESULTS: The model has been used successfully to demonstrate, teach, and practice adult circumcision as well as other penile procedures with rating by trainees ranged from 7 to 10 (median: 9), and 9 of 12 trainees commented on the model using expressions such as "life like," "excellent idea," or "extremely beneficial." CONCLUSIONS: The model is particularly useful as it is life like, realistic, easy to set up, and can be used to repeatedly demonstrate circumcision, as well as other surgical procedures, such as dorsal slit and paraphimosis reduction. PMID- 22677580 TI - Novel educational approach for medical students: improved retention rates using interactive medical software compared with traditional lecture-based format. AB - BACKGROUND: Mannequin and computer-based simulators are useful for the practice of patient management, physical procedures, and competency. However, they are ineffective in teaching clinical medicine. StepStone Interactive Medical Software (SS) is a web-based medical learning modality that provides the user with a highly focused set of evaluative and interventional tasks to treat memorable virtual patients in a visual case-based format. OBJECTIVE: To determine whether the SS learning modality is superior to traditional lecture format in medical student learning and retention. METHODS: After Institutional Review Board (IRB) approval was obtained and the consents were signed, 30 third-year medical students were assigned randomly to 2 groups of 15 students each: The control group received two 30-minute PowerPoint lectures (Microsoft Corporation, Redmond, Washington) about torsades de pointes (TdP) and pulseless electrical activity (PEA), and the SS group was given 1 hour to review 2 SS cases teaching TdP and PEA. A preintervention test was given to assess their baseline knowledge. An immediate postintervention test was given to both groups. Twenty-two days later, a long-term retention test was administered. The results were analyzed using a Student t test for continuous variables. RESULTS: The mean scores for the preintervention test in the control and SS groups were 44.9 +/- 3% and 44.1 +/- 2%, respectively (p = 0.41). The mean scores for the postintervention test in the control and SS groups were 61.7 +/- 2% and 86.7 +/- 2%, respectively (p < 0.001). Improvement from baseline knowledge was calculated, and the mean improvement was 16.8 +/- 3% in the control group and 42.5 +/- 2% in the SS group (p < 0.001). The long-term retention test revealed the mean scores of 55.8 +/- 3% in the control group and 70.1 +/- 3% in the SS group (p < 0.001). Long-term improvement from baseline knowledge was calculated and the control group improved by 10.9 +/- 4%, whereas the SS group improved by 26 +/- 3% (p = 0.002). CONCLUSIONS: The SS learning modality demonstrated a significant improvement in student learning retention compared to traditional didactic lecture format. SS is an effective web based medical education tool. PMID- 22677581 TI - A prospective study of heart rate variability in endocrine surgery: surgical training increases consultant's mental strain. AB - BACKGROUND: The aim of this study was to determine whether instructing surgical trainees in technically demanding procedures causes alterations in heart rate variability (HRV) and mental strain in supervising surgeons. METHODS: A prospective study of HRV in two consultant surgeons and three endocrine surgical fellows undertaking 50 total thyroidectomy procedures was performed. Fellows and consultant surgeons performed 50 lobectomies as primary operator and 50 as assistants in a cross-over design. HRV was measured during dissection around the recurrent laryngeal nerve. The overall heart rate, time, and frequency domain parameters of HRV, specifically the low frequency/high frequency (LF/HF) ratio, which was used as a measure of cardiac and mental stress, were correlated with the surgical role, particularly teaching surgical fellows at critical points. RESULTS: HRV data were collected between October 2009 and March 2010. There was no statistically significant difference in the mean heart rate for either group of participants regardless of role. Energy expenditure was greater for fellows when operating (p = 0.03). Fellows demonstrated a higher LF/HF ratio when acting as the primary operator (p = 0.02). All time domain parameters of HRV increased when attending surgeons were operating, denoting more cardiac relaxation. Similarly, the LF/HF ratio was significantly greater for attending surgeons when teaching (p = 0.05), suggesting an increase in mental strain. CONCLUSIONS: The teaching of complex but common endocrine surgical procedures is associated with a measurable increase in mental strain of consultant surgeons, as determined by HRV. Fellows demonstrated increased levels of stress when acting as primary operators. PMID- 22677582 TI - Basic laparoscopic training using the Simbionix LAP Mentor: setting the standards in the novice group. AB - BACKGROUND: Virtual reality devices are becoming the backbone for laparoscopic training in surgery. However, without knowledge of the achievable metrics of basic training within the trainee group, these simulators cannot be used effectively. Currently, no validated task metrics of the performance of larger trainee groups are available. STUDY DESIGN: From April 2004 to December 2009, we collated an extensive prospective database using the Simbionix LAP Mentor (Simbionix USA, Cleveland, Ohio) for basic laparoscopic training of novice surgeons. This database was used to determine benchmarks for basic skill exercises and procedural tasks that combine stimulus to improve and feasibility with acceptance of the training program and the goal to train for safe surgery. RESULTS: In all, 18,996 task performances of 286 novice trainees were analyzed. For the basic skill exercises, the total time for correct execution ranged between 45 seconds for basic skill 3 (eye-hand coordination) and 269 seconds for basic skill 9 (object placement). For the procedural tasks, the total time for correct execution ranged between 68 seconds for procedural task 1 (clipping and cutting) and 256 seconds for procedural task 3 (dissection). The total time to task completion depended mainly on right instrument path length with high correlation to left instrument path length. Learning curve analyses of the 4 procedural tasks demonstrated performance plateaus after 10-15 repetitions. Most complications occurred during the initial repetitions of the respective task. The best quartile of performances was chosen as peer group benchmark because it provides sufficient stimulus for improvement without discouraging trainees, thus enhancing adherence to the training program. The benchmark for safety and accuracy parameters was set at a predefined level of 95% correct execution. CONCLUSIONS: As experience with virtual reality (VR) training is growing, curricula must be based on benchmarks for efficient training derived from large trainee groups to optimize use of the still costly simulators. Safety parameters should be included in trainee assessment. We share a set of metrics that take into account both performance and feasibility for basic laparoscopic training of surgical novices using the Simbionix LAP Mentor. PMID- 22677583 TI - Can residents safely and efficiently be taught single incision laparoscopic cholecystectomy? AB - OBJECTIVE: Single incision laparoscopic cholecystectomy (SILC) has recently emerged as an option for selected patients undergoing gallbladder removal. While SILC appears safe when performed by experienced surgeons under controlled conditions, there are no studies evaluating the SILC learning curve for incorporation into resident education and the effect on OR efficiency. DESIGN, SETTING, AND PARTICIPANTS: Chief residents were taught and evaluated by a single attending surgeon facile with SILC techniques. Residents were transitioned from assistants to primary surgeon during their clinical rotation. Outcomes data were prospectively tabulated compared with data from standard laparoscopic SLC and attending surgeon SILC outcomes. The setting was an academic, tertiary care teaching hospital. Participants were chief residents rotating on hepatobiliary surgery service. Residents previously had demonstrated mastery of basic laparoscopic surgical techniques. RESULTS: Seven chief residents were evaluated with a total of 49 SILCs with a mean of 7 (range 5-12) SILCS/resident. Five conversions to SLC occurred, all within the first 3 SILCs performed by the resident as operative surgeon. Mean blood loss was 30 mL. Median length of stay was <1 day. Average length of operation increased after the first 2 cases, reflecting the transition of the attending surgeon from primary surgeon to assistant role. By the fifth case, operative times returned to the attending surgeon SILC baseline and historical operative times for SLC at our institution. Factors associated with longer-length of surgery were increasing BMI and presence of acute or chronic cholecystitis, choledocholithiasis, and use of intraoperative cholangiogram. Five postoperative complications occurred and were not associated with position along the resident's learning curve. One death occurred due to metastatic laryngeal cancer within 30 days of SILC. CONCLUSIONS: Residents can safely be taught the techniques of SILC with minimal disruption to operating room efficiency. Residents already proficient in the use of standard laparoscopic techniques transition to SILC quickly with a short learning curve and proper instruction. PMID- 22677584 TI - Cutting errors in surgery: experience limits underestimation bias in a simulated surgical environment. AB - OBJECTIVE: Error management is crucial in surgery and needs to be developed through appropriate training and education. Research suggests that perceptual errors may be more likely in laparoscopic environments. The objective of this work is to investigate error management by novices compared with experienced surgeons when performing a simple simulated incision in a visually challenging environment. METHODS: Novices (n = 20) and experienced surgeons (n = 11) viewed pairs of horizontal lines on a laparoscopic monitor. Participants were asked to replicate the line lengths by making simulated incisions. The task was completed with or without online visual feedback of the incising hand. In a second phase of the study, the task was complicated by embedding the lines within a perceptual illusion (i.e., Ponzo illusion). RESULTS: Incision lengths generally were shorter than the actual lengths of the viewed lines for all participants. For the novices, however, this underestimation bias was exacerbated when visual feedback of the incising hand was unavailable (p < 0.001), whereas the surgeons were not affected by loss of vision of the incising hand (p = 0.864). Furthermore, novices were influenced by the perceptual illusion designed to alter perceptions of line length (p = 0.021), whereas the surgeons did not appear to be influenced by the illusion (p = 0.945). CONCLUSIONS: A perceptual bias towards incision length underestimation may be present when surgery involves a laparoscopic monitor; however, surgical experience may protect against accentuation of the underestimation bias when the task becomes more visually challenging. The bias is discussed using the framework of error management theory. PMID- 22677585 TI - E-learning resources for vascular surgeons: a needs analysis study. AB - OBJECTIVES: To obtain the views of vascular surgeons about online resources in their specialty as a guide to future e-learning development. DESIGN: A focused questionnaire regarding e-learning resources in vascular surgery was circulated online. A combination of structured and open-ended questions addressed users' ranking of various resource types, examples of presently used websites, suggestions for future growth, and the opportunity to become actively involved in e-learning development. The responses were collected over a 4-week period and remained anonymous. SETTING: The study was conducted online at http://www.vasculareducation.com as part of an ongoing project on e-learning for vascular surgeons by the Department of Educational Development and Research, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands. PARTICIPANTS: The survey population consisted of vascular surgeons and surgical trainees in Europe. The participants were contacted via their membership of the European Society for Vascular Surgery and national academic or administrative vascular surgical organizations. Demographic information was collected about clinical seniority and country of work. RESULTS: In all, 252 responses were obtained. Respondents favored the development of a variety of online resources in vascular surgery. The strongest demand was for illustrations and videos of surgical techniques, followed by an interactive calendar and peer-reviewed multiple-choice questions. Overall, 46% of respondents wished to contribute actively toward e-learning development, with consultants being more willing than trainees to do so. CONCLUSIONS: Members of the vascular surgical community value online resources in their specialty, especially for procedural techniques. Vascular surgeons would like to be actively involved in subsequent development of e-learning resources. PMID- 22677586 TI - From theater to the world wide web--a new online era for surgical education. AB - INTRODUCTION: Traditionally, surgical education has been confined to operating and lecture theaters. Access to the World Wide Web and services, such as YouTube and iTunes has expanded enormously. Each week throughout Ireland, nonconsultant hospital doctors work hard to create presentations for surgical teaching. Once presented, these valuable presentations are often never used again. AIMS: We aimed to compile surgical presentations online and establish a new online surgical education tool. We also sought to measure the effect of this educational tool on surgical presentation quality. METHODS: Surgical presentations from Cork University Hospital and Beaumont Hospital presented between January 2010 and April 2011 were uploaded to http://www.pilgrimshospital.com/presentations. A YouTube channel and iTunes application were created. Web site hits were monitored. Quality of presentations was assessed by 4 independent senior surgical judges using a validated PowerPoint assessment form. Judges were randomly given 6 presentations; 3 presentations were pre-web site setup and 3 were post-web site setup. Once uploading commenced, presenters were informed. RESULTS: A total of 89 presentations have been uploaded to date. This includes 55 cases, 17 journal club, and 17 short bullet presentations. This has been associated with 46,037 web site page views. Establishment of the web site was associated with a significant improvement in the quality of presentations. Mean scores for pre- and post-web site group were 6.2 vs 7.7 out of 9 respectively, p = 0.037. CONCLUSIONS: This novel educational tool provides a unique method to enable surgical education become more accessible to trainees, while also improving the overall quality of surgical teaching PowerPoint presentations. PMID- 22677587 TI - Implications of current resident work-hour guidelines on the future practice of surgery in Canada. AB - OBJECTIVE: Work-hour restrictions have had a profound impact on surgical training. However, little is known of how work-hour restrictions may affect the future practice patterns of current surgical residents. The purpose of this study is to compare the anticipated career practice patterns of surgical residents who are training within an environment of work-hour restrictions with the current practice of faculty surgeons. DESIGN: An electronic survey was sent to all surgery residents and faculty at 2 Canadian university-affiliated medical centers. The survey consisted of questions regarding expected (residents) or current (faculty) practice patterns. RESULTS: A total of 149 residents and 125 faculty members completed the survey (50.3% and 52.3% response rates, respectively). A greater proportion of males were in the faculty cohort than in the resident group (77.6% vs 62.4%, p = 0.0003). More faculty than residents believed that work-hour restrictions have a negative impact on both residency education (40.8% vs 20.8%, p = 0.008) and preparation for a surgical career (56.8% vs 19.5%, p < 0.0001). Compared with current faculty, residents plan to take less call (p < 0.0003), work fewer days of the week (p < 0.0001), are more likely to limit their duty hours on postcall days (p = 0.009), and take parental leave (p = 0.02) once in practice. Male and female residents differed somewhat in their responses in that more female residents plan to limit their postcall duty hours (55.4% vs 36.5%, p = 0.009) and to take a parental leave (51.8% vs 16.1%, p < 0.0001) compared with their male resident colleagues. CONCLUSIONS: Current surgical residents expect to adopt components of resident work-hour guidelines into their surgical practices after completing their residency. These practice patterns will have surgical workforce implications and might require larger surgical groups and reconsideration of resource allocation. PMID- 22677588 TI - Master surgeons' operative teaching philosophies: a qualitative analysis of parallels to learning theory. AB - OBJECTIVES: Practicing within the Halstedian model of surgical education, academic surgeons serve dual roles as physicians to their patients and educators of their trainees. Despite this significant responsibility, few surgeons receive formal training in educational theory to inform their practice. The goal of this work was to gain an understanding of how master surgeons approach teaching uncommon and highly complex operations and to determine the educational constructs that frame their teaching philosophies and approaches. DESIGN: Individuals included in the study were queried using electronically distributed open-ended, structured surveys. Responses to the surveys were analyzed and grouped using grounded theory and were examined for parallels to concepts of learning theory. SETTING: Academic teaching hospital. PARTICIPANTS: Twenty-two individuals identified as master surgeons. RESULTS: Twenty-one (95.5%) individuals responded to the survey. Two primary thematic clusters were identified: global approach to teaching (90.5% of respondents) and approach to intraoperative teaching (76.2%). Many of the emergent themes paralleled principles of transfer learning theory outlined in the psychology and education literature. Key elements included: conferring graduated responsibility (57.1%), encouraging development of a mental set (47.6%), fostering or expecting deliberate practice (42.9%), deconstructing complex tasks (38.1%), vertical transfer of information (33.3%), and identifying general principles to structure knowledge (9.5%). CONCLUSIONS: Master surgeons employ many of the principles of learning theory when teaching uncommon and highly complex operations. The findings may hold significant implications for faculty development in surgical education. PMID- 22677589 TI - Measuring the surgical academic output of an institution: the "institutional" H index. AB - INTRODUCTION: The Hirsch index is a novel index that combines the number of publications and citations in measuring the research output of researchers. We hypothesized that the h-index can be used to measure the academic success of an institution in a subject area (surgery) and compared this measure to previously published measures of ranking institutions. METHODS: We identified the top 10 research medical schools as designated by the United States News and World Report 2010. The h-index for an institution was obtained in 3-year periods for articles published in surgery. Independent rankings from the NIH and other web sites were then used to compare with our newly generated rankings. RESULTS: The median h index for institutions was 52.5 (46-54) for 2000-2002, 50 (44-52) for 2003-2005, 35.5 (33-40) for 2006-2008, and 15.5 (13-16) for 2009-2011. The percentage of self citations was the highest in publications from Harvard University (22.2%) and the lowest from Columbia University (10%) in the years 2009-11. Our ranking closely mirrored the United States News and World Report, and Harvard Medical School remains the top ranking in the field of surgery, although NIH funding based ranking may suggest otherwise. CONCLUSIONS: The institutional h-index appears to be a viable indicator for the measure of academic success of institutions in a subject area. Despite limitations, it yields objective data regarding the citations and number of articles published by an institution in a subject area and could be used to measure performance. PMID- 22677590 TI - Objective assessment of surgical training in flexor tendon repair: the utility of a low-cost porcine model as demonstrated by a single-subject research design. AB - OBJECTIVES: This study evaluated the utility of a porcine flexor tendon model and standard biomechanical testing procedures to quantify the acquisition of surgical skills associated with Zone II flexor tendon repair in a trainee by benchmarking task performance outcomes relative to evidence-based standards. STUDY DESIGN: Single-subject repeated measures research design. Bench-top set-up of apparatus undertaken in a University Research laboratory. After initial directed learning, a trainee repaired 70 fresh flexor digitorum profundus tendons within the flexor sheath using either a Pennington or ventral-locking-loop modification of a two strand Kessler core repair. Tendon repairs were then preconditioned and distracted to failure. Key biomechanical parameters of the repair, including the ultimate tensile strength (UTS), yield strength, 3 mm gap force and stiffness, were calculated. Repairs were divided into 3 categories, early (first 10 days), intermediate (ensuing 10 days), and late repairs (final 10 days), and potential changes in repair properties over the training period were evaluated using a general linear modeling approach. RESULTS: There was a significant change in the mechanical characteristics of the repairs over the training period, evidencing a clear learning effect (p < 0.05). Irrespective of the repair technique employed, early and intermediate repairs were characterized by a significantly lower UTS (29% and 20%, respectively), 3 mm gap (21% and 16%, respectively), and yield force (18% and 23%, respectively), but had a higher stiffness (33% and 38%, respectively) than late repairs (p < 0.05). The UTS of late repairs (47-48 N) were comparable to those published within the literature (45-51 N), suggesting surgical competence of the trainee. CONCLUSIONS: This simple, low-cost porcine model appears to be useful for providing preclinical training in flexor tendon repair techniques and has the potential to provide a quantitative index to evaluate the competency of surgical trainees. Further research is now required to identify optimal training parameters for flexor tendon repair and to develop procedure-specific standards for adequate benchmarking. PMID- 22677591 TI - Reliable and valid tools for measuring surgeons' teaching performance: residents' vs. self evaluation. AB - BACKGROUND: In surgical education, there is a need for educational performance evaluation tools that yield reliable and valid data. This paper describes the development and validation of robust evaluation tools that provide surgeons with insight into their clinical teaching performance. We investigated (1) the reliability and validity of 2 tools for evaluating the teaching performance of attending surgeons in residency training programs, and (2) whether surgeons' self evaluation correlated with the residents' evaluation of those surgeons. MATERIALS AND METHODS: We surveyed 343 surgeons and 320 residents as part of a multicenter prospective cohort study of faculty teaching performance in residency training programs. The reliability and validity of the SETQ (System for Evaluation Teaching Qualities) tools were studied using standard psychometric techniques. We then estimated the correlations between residents' and surgeons' evaluations. RESULTS: The response rate was 87% among surgeons and 84% among residents, yielding 2625 residents' evaluations and 302 self evaluations. The SETQ tools yielded reliable and valid data on 5 domains of surgical teaching performance, namely, learning climate, professional attitude towards residents, communication of goals, evaluation of residents, and feedback. The correlations between surgeons' self and residents' evaluations were low, with coefficients ranging from 0.03 for evaluation of residents to 0.18 for communication of goals. CONCLUSIONS: The SETQ tools for the evaluation of surgeons' teaching performance appear to yield reliable and valid data. The lack of strong correlations between surgeons' self and residents' evaluations suggest the need for using external feedback sources in informed self evaluation of surgeons. PMID- 22677592 TI - Teaching and assessing technical proficiency in surgical subspecialty fellowships. AB - OBJECTIVES: To determine how programs are teaching and assessing procedural skills, and their perceived success. DESIGN: Cross-sectional survey. SETTING: Accreditation Council for Graduate Medical Education (ACGME) approved training programs in pediatric urology and colorectal surgery. PARTICIPANTS: Program directors and recent graduates (2007-2009). RESULTS: Thirty-nine program directors (60%), and 57 graduates (64%) responded; 89.5% of graduates and 94.9% of program directors felt training occurred successfully for the procedures that trainees were performing in their present practice. Nearly 90% of trainees and all program directors reported that there was no formal assessment of procedural competency at the beginning of training, although 66.7% of program directors reported that trainees were assessed "informally." Both program directors and trainees reported dialogue with faculty was the most frequent method used in preparing for operative procedures. Other methods (textbook/atlas, journals, web based programs, videos) were used less frequently. Program directors with shorter tenure were more likely to use web-based and video methods; younger trainees were less likely to use textbooks/atlases. Faculty feedback on clinical decision making and postprocedural review were perceived by both program directors and trainees as the most effective assessment methods for improving performance; however, trainees were more likely than program directors to report that postprocedure reviews were not included in their training (15.8% vs 9%, p = 0.045). Patient outcomes, written feedback from peers, and self-assessment were included in most programs, but valued less. Simulation was used in only about half the programs and was valued more highly by trainees than program directors (p = 0.011). CONCLUSIONS: Training in procedural proficiency was viewed as successful by both program directors and graduates. Dialogue with, assessment by, and feedback from faculty were frequently used and most valued; stressing the importance of the facilitator role of faculty in the education of the trainee. These findings provide guidance for the development of newer methods of teaching and assessment. PMID- 22677593 TI - Technical skills acquisition in surgery-bound senior medical students: an evaluation of student assertiveness. AB - OBJECTIVE: To prepare students pursuing surgical careers, we devised a senior subinternship curriculum supplement that focused on the acquisition of technical skills required of surgical residents. We hypothesized that more assertive students, those that accomplished more of the curriculum, would perform better on a technical skills Objective Structured Clinical Examination (OSCE). DESIGN: Senior medical students rotating on their first general surgery subinternship were administered a 6-station OSCE on the first day of their subinternship and again during the final week of the month-long rotation. A self-directed, 38-task "scavenger hunt" representing common intern level clinical skills, procedures, and patient care activities was provided to each student. SETTING: The study was performed at Jefferson Medical College, a large, private medical school in Philadelphia, PA. PARTICIPANTS: Forty-nine senior students completed surgical subinternships between July 2009 and September 2010, and participated both in the pre-/post-OSCEs and the scavenger hunt. RESULTS: Students performed significantly better on the post-rotation OSCE than on the pre-rotation OSCE; 70.2% +/- 8.1% vs. 60.4% +/- 12.0%, p < 0.0001. Assertiveness scores from the "scavenger hunt" did not correlate with final OSCE scores (r = -0.328, p = 0.25), and were negatively correlated with the change between pre- and post-OSCE scores (r = 0.573, p < 0.04). Individual student assertiveness scores were determined by the number of tasks completed over the course of the rotation. CONCLUSIONS: As surgical education becomes more streamlined with evolving work hour restrictions, medical school education is playing an increasingly pivotal role in preparing students for internship. In our study, individual assertiveness in completing structured self-directed learning tasks did not directly predict the acquisition of proficiency in technical skills. We feel assertiveness is overshadowed by other factors that may carry more weight in terms of technical skills acquisition. Further studies are required to delineate these factors and ultimately enhance technical skills acquisition during medical school. PMID- 22677594 TI - The effect and durability of a pregraduation boot cAMP on the confidence of senior medical student entering surgical residencies. AB - OBJECTIVE: Medical school does not specifically prepare students for surgical internship. Preinternship courses are known to increase confidence in multiple key areas. We examined the immediate effect and durability of effect of a surgical pregraduation preparatory course or "boot camp" on provider confidence in technical and medical management skills. DESIGN: A 5-day boot camp was offered to senior medical students (SMS) entering surgical programs. SMS were anonymously surveyed before, after, and 6 months following the course. The same survey was given 6 months into internship to a control group of surgical interns who graduated from the same medical school but did not participate in boot camp before graduation. Data were compared between the time intervals and across cases and controls using the Wilcoxon rank-sum and signed-rank tests and the Student t test. SETTING: A joint effort between the University of Pennsylvania School of Medicine, the Department of Surgery at the Hospital of the University of Pennsylvania, and the Penn Medicine Simulation Center in Philadelphia, PA. PARTICIPANTS: All senior medical students set to graduate from a single institution entering general surgery or surgery subspecialties were offered the course. Twenty-nine students participated in the course. RESULTS: Post-boot camp confidence scores of SMS were significantly greater in all areas except placement of a peripheral intravenous catheter compared with pre-boot camp scores. Six months into internship, the SMS boot camp group felt more confident than controls in their ability to perform a cricothyroidotomy (median 2.5 vs 1.0, p = 0.04) and to insert a chest tube (median 3.3 vs 1.0, p = 0.05). Otherwise, there was no residual difference in confidence levels between the boot camp group and the controls. CONCLUSIONS: Boot camps can improve self-confidence in young doctors in many areas of perioperative care before enrolling in surgical residency. The effect is most durable in high risk, infrequently performed technical tasks. Future studies are under design to examine the impact of boot camps on the "July Effect." PMID- 22677595 TI - The effect of general surgery clerkship rotation on the attitude of medical students towards general surgery as a future career. AB - BACKGROUND: Literature suggests declining interest in General Surgery (GS) and other surgical specialties, with fewer Canadian medical residency applicants identifying a surgical specialty as their first choice. Although perceptions of surgical careers may begin before enrollment in clerkship, clerkship itself provides the most concentrated environment for perceptions to evolve. Most students develop perceptions about specialties during their clinical clerkships. This study examines the immediate impact of GS clerkship on student attitudes toward GS as a career, and on preferences towards GS compared with other specialties. METHODS: A pre-post design involved 61 McMaster clinical clerks. Two instruments were used to collect data from students over the course of clerkship (2008-2009). Paired comparison (PC) compared ranking of career choices before and after clerkship. Semantic differential (SD) measured attitudes toward GS and variables that may have affected attitudes before and after clerkship. Analyses used SPSS 16.0 (SPSS Inc., Chicago, IL). RESULTS: Clerks ranked preferences for GS changed substantially after clerkship, moving from the 10th to the 5th position compared with other specialties. Ranks of surgical subspecialties also changed, though GS demonstrated the largest improvement. SD results were consistent with PC, showing improved attitudes after rotation, with differences both statistically and practically significant (t = 3.81, p < 0.000, effect size = 0.23). Results indicated that attitudes toward all areas related to GS clerkship (attending physicians, surgical residents, ward nurses, scrub nurses, workload, knowledge achieved, technical skills acquired) improved significantly except attitude toward technical skills acquired. CONCLUSIONS: Clinical clerkship at McMaster was a positive experience and significantly enhanced preferences towards GS and attitudes towards GS as a career. Medical schools should foster positive interaction between clinical clerks and staff (including attending surgeons and nurses), ensure that teaching hospital staff provide a positive experience for clerks, and should provide opportunities to learn basic technical skills during GS clerkship. PMID- 22677596 TI - The 3-finger technique in establishing percutaneous renal access: a new and simple method for junior trainees. AB - INTRODUCTION AND OBJECTIVES: Urology trainees may lack experience in gaining renal access during percutaneous nephrolithomy (PCNL). Establishing the correct depth of initial percutaneous needle insertion is one of the major obstacles. As such, we have identified an easy technique, which can be performed, to establish correct depth adjustment allowing easier access. MATERIALS AND METHODS: An initial attempt is made to insert the percutaneous needle into the desired posterior calyx in the antero-posterior (AP) plane. If the needle does not traverse into the desired calyx immediately, it is concluded that the needle track must be too shallow or too deep. The C-arm is then rotated 20 to 30 degrees from the vertical, in the axial plane, towards the operating surgeon and, using the image intensifier, very careful note is made of the end of the needle in this plane, compared with the end of the needle initially in the AP plane, to see if it has moved "medially" or "laterally." The 3-finger technique is then performed by the surgeon, to establish if the needle path is too deep or too shallow. This technique is currently being performed by trainees under direct consultant supervision with 13 successful cases so far. RESULTS: The 3-finger technique has been successfully used to demonstrate and teach PCNL access to urology trainees. In all 13 cases, percutaneous renal access was achieved successfully by trainees without immediate or late complications. Also, positive and encouraging feedbacks were received from those trainees, and all expressed willingness to continue using the same new technique in the future. CONCLUSIONS: Our new technique is cheap, safe, easy to learn and use, and of particular benefit to junior trainees who are beginning to perform PCNL access. PMID- 22677597 TI - The utility of the ABS in-training examination (ABSITE) score forms: percent correct and percentile score in the assessment of surgical residents. AB - OBJECTIVE: The American Board of Surgery (ABS) provides program directors with ABS In-Training Examination (ABSITE) scores in the following forms: Percent correct score and percentile score. It is of interest to note how residency programs utilize the different forms of ABSITE scores in assessment of surgical residents for progression in training. We conducted a survey of program directors to ascertain the present situation. METHODS: A structured questionnaire was sent to all program director members of the Association of Program Directors in Surgery. RESULTS: 114/210 program directors (54%) answered the survey. To assess residents, 3 programs used only the percentage correct score, 23 programs used only the percentile score, and 88 programs used both scores. The majority (70/89 or 79%) of the programs used a 30th percentile score as the minimum passing score. 88/111 (79%) programs had a remedial process for residents with poor performance on ABSITE. 60 percent of the programs had never used poor ABSITE performance to defer individual resident promotion. Programs that used ABSITE performance for remediation and deferral of promotion did it based on percentile score rather than percent correct score. Program directors felt that the better indicator of a resident's knowledge and progression in surgical residency was percent correct score (42%) vs percentile score (32%), while 10% felt that neither was an adequate indicator. CONCLUSIONS: ABSITE score is being used as one of the measures to assess residents. Programs need to ensure that an effective remedial process is in place to assist residents with poor performance. PMID- 22677598 TI - Training of surgical endoscopists in Korea: assessment of the learning curve using a cumulative sum model. AB - OBJECTIVE: Surgeons' interest and participation in endoscopy have increased recently. The aims of the present study were to assess the learning curve for surgical training in upper endoscopy and to suggest an appropriate training program for surgeons in Korea. DESIGN: Under the supervision of skilled endoscopists, 4 trainees who participated in this study performed more than 150 esophagogastroduodenoscopy procedures, according to the recommendations of the American Society for Gastrointestinal Endoscopy. The success of the procedures was defined as the fulfillment of designated time and checkpoints. A cumulative sum model was used to assess the learning curve. RESULTS: During the same period, the 4 trainees completed 158, 160, 166, and 180 procedures, respectively. Plateau points occurred on the learning curve at the 81st, 90th, 98th, and 111th case in the cumulative sum model and the mean value of the plateau was the 95th case. CONCLUSIONS: An intensive education tool and training module that meets the conditions of surgical residents is mandatory for the training of proficient surgical endoscopists. PMID- 22677599 TI - Voluntary autonomous simulator based training in minimally invasive surgery, residents' compliance and reflection. AB - BACKGROUND: Knot tying and suturing skills in minimally invasive surgery (MIS) differ markedly from those in open surgery. Appropriate MIS training is mandatory before implementation into practice. The Advanced Suturing Course (ASC) is a structured simulator based training course that includes a 6-week autonomous training period at home on a traditional laparoscopic box trainer. Previous research did not demonstrate a significant progress in laparoscopic skills after this training period. This study aims to identify factors determining autonomous training on a laparoscopic box trainer at home. METHODS: Residents (n = 97) attending 1 of 7 ASC courses between January 2009 and June 2011 were consecutively included. After 6 weeks of autonomous, training a questionnaire was completed. A random subgroup of 30 residents was requested to keep a time log. All residents received an online survey after attending the ASC. We performed outcome comparison to examine the accuracy of individual responses. RESULTS: Out of 97 residents, the main motives for noncompliant autonomous training included a lack of (training) time after working hours (n = 80, 83.3%), preferred practice time during working hours (n = 76, 31.6%), or another surgical interest than MIS (n = 79, 15.2%). Previously set training goals would encourage autonomous training according to 27.8% (n = 18) of residents. Thirty participants submitted a time log and reported an average 76.5-minute weekly training time. All residents confirmed that autonomous home practice on a laparoscopic box trainer is valuable. CONCLUSIONS: Autonomous practice should be structured and inclusive of adequate and sufficient feedback points. A minimally required practice time should be set. An obligatory assessment, including corresponding consequence should be conducted. Compliance herewith may result in increased voluntary (autonomous) simulator based (laparoscopic) training by residents. PMID- 22677600 TI - Functional characterization and immune recognition of the extracellular superoxide dismutase from the human pathogenic parasite Onchocerca volvulus (OvEC SOD). AB - Onchocerca volvulus is a human pathogenic filarial nematode causing chronic onchocerciasis, a disease characterized by chronic skin and eye lesions. Despite attempts to control this infection from many perspectives, it still remains a threat to public health because of adverse effects of available drugs and recent reports of drug resistance. Under control of an intact immune system, O. volvulus survives for a long time in the host by employing a variety of strategies including the utility of antioxidant enzymes. In the present study, we focus on the extracellular superoxide dismutase from O. volvulus (OvEC-SOD) found in the excretory/secretory products of adult worms. Contrary to previous studies, the OvEC-SOD was found to have a 19 amino acid long signal peptide that is cleaved off during the process of maturation. To validate this result, we designed a novel method based on Caenorhabditis elegans cup5(ar465) mutants to specifically evaluate signal peptide-mediated secretion of nematodal proteins. Following purification, the recombinant OvEC-SOD was active as a dimer. Site-directed mutagenesis of the three cysteines present in the OvEC-SOD shows that enzyme activity is markedly reduced in the Cys-192 mutant. A homology model of the OvEC SOD underlines the importance of Cys-192 for the stabilization of the adjacent active site channel. The generation of a humoral immune response to secretory OvEC-SOD was indicated by demonstrating IgG reactivity in sera from patients infected with O. volvulus while the cross-reactivity of IgG in plasma samples from cows, infected with the most closely related parasite Onchocerca ochengi, occurred only marginally. High IgG1 and IgM titres were recorded in sera from mice infected with the filaria Litomosoides sigmodontis, however, low or no cellular proliferative responses were observed. Thus, the present data suggest that secretory OvEC-SOD is a target of the humoral immune response in human onchocerciasis and induced strongest IgG responses in hyperreactive onchocerciasis. Furthermore, humoral response during murine infection induced SOD specific IgG that cross-reacted with OvEC-SOD. PMID- 22677601 TI - The ITS2 of the genus Bulinus: novel secondary structure among freshwater snails and potential new taxonomic markers. AB - The freshwater snail genus Bulinus has been intensively investigated due to its role as intermediate host for trematode blood flukes that cause the debilitating disease schistosomiasis in man and livestock. Owing to taxonomic ambiguities within Bulinus, attention has often focused upon species delineation and several molecular methods have recently been used for identification and characterization purposes. Inspection of compensatory base changes (CBCs) in the secondary structure of the nuclear ribosomal internal transcribed spacer (ITS) has been used to differentiate species in other genera, and here we present a study investigating the presence of CBCs between species in the species groups within Bulinus. CBCs were present within B. forskalii and B. globosus indicating that these widely distributed taxa might constitute cryptic species complexes. However, other currently recognized species could not be distinguished by CBC analysis. The putative secondary structure of the very long ITS2 sequence of the B. reticulatus species group had an additional helix (DIIa) between DII and DIII not seen in other species groups of Bulinus. The accumulation and inspection of further ITS2 sequences will no doubt reveal additional variation between Bulinus populations, and CBCs should be incorporated in future taxonomic work in this group. PMID- 22677602 TI - Highly discriminatory typing method for Listeria monocytogenes using polymorphic tandem repeat regions. AB - Tandem repeats (TR), which are repetitive nucleotide sequences in DNA, are polymorphic both in repeat number and sequence. In this study, we developed a new typing method, multilocus TR sequence analysis (MLTSA), for the foodborne pathogen Listeria monocytogenes using sequence polymorphisms in three tandem repeat regions. The obtained dendrogram clustered L. monocytogenes strains of lineage I and lineage II separately, and formed three groups within the lineage I cluster, each of which included one of the three major L. monocytogenes epidemic clones (ECI, ECIa, and ECII). These results were consistent with a previously established virulence-gene-based MLST method. In comparison, our method grouped some epidemiologically related isolates together, which virulence-gene-based MLST did not. Moreover, our method, using three tandem repeat regions, showed a higher discriminatory power than the MLST method, which uses six virulence gene regions. This MLTSA approach using sequence polymorphisms in TR regions could be a useful tool in the epidemiological study of L. monocytogenes. PMID- 22677603 TI - Detection of Bacillus anthracis from spores and cells by loop-mediated isothermal amplification without sample preparation. AB - Loop-mediated isothermal amplification (LAMP) is a technique capable of rapidly amplifying specific nucleic acid sequences without specialized thermal cycling equipment. In addition, several detection methods that include dye fluorescence, gel electrophoresis, turbidity and colorimetric change, can be used to measure or otherwise detect target amplification. To date, publications have described the requirement for some form of sample nucleic acid extraction (boiling, lysis, DNA purification, etc.) prior to initiating a LAMP reaction. We demonstrate here, the first LAMP positive results obtained from vegetative cells and spores of Bacillus anthracis without nucleic acid extraction. Our data show that the simple addition of cells or spores to the reaction mixture, followed by heating at 63 degrees C is all that is required to reproducibly amplify and detect target plasmid and chromosomal DNA via colorimetric change. The use of three primer sets targeting both plasmids and the chromosome of B. anthracis allows for the rapid discrimination of non-pathogenic bacteria from pathogenic bacteria within 30 min of sampling. Our results indicate that direct testing of B. anthracis spores and cells via LAMP assay will greatly simplify and shorten the detection process by eliminating nucleic acid purification. These results may allow more rapid detection of DNA from pathogenic organisms present in field and environmental samples. PMID- 22677604 TI - Development and characterization of a Pseudomonas aeruginosa in vitro coupled transcription-translation assay system for evaluation of translation inhibitors. AB - Bacterial transcription and translation have proven to be effective targets for broad-spectrum antimicrobial therapies owing to the critical role they play in bacterial propagation and the overall conservation of the associated machinery involved. Escherichia coli is the most common source of S30 extract used in bacterial in vitro coupled transcription-translation assays, however, transcription-translation assays in other important pathogens including Staphylococcus aureus and Streptococcus pneumoniae have been described (Murray et al., 2001; Dandliker et al., 2003). Pseudomonas aeruginosa is an important and difficult-to-treat Gram-negative pathogen. In a drug discovery program, to de risk any potential species specificity of novel inhibitors, we developed and optimized a robust method for the preparation of S30 extract from P. aeruginosa strain PAO1. Further, a P. aeruginosa transcription-translation assay using a firefly luciferase reporter plasmid was validated and compared to an E. coli S30 based system using a wide range of antibiotics encompassing multiple classes of translation inhibitors. Results showed a similar ranking of the activities of known inhibitors, illustrative of the high degree of conservation between the transcription-translation pathways in both organisms. PMID- 22677605 TI - Development of a risk-based methodology for estimating survival and growth of enteropathogenic Escherichia coli on iceberg-lettuce exposed at short-term storage in foodservice centers. AB - Ready-to-eat lettuce is a food commodity prone to contamination by pathogenic microorganisms if processing and distribution conditions as well as handling practices are not effective. A challenge testing protocol was applied to ready-to eat iceberg-lettuce samples by inoculating different initial contamination levels (4.5, 3.5 and 2.5 log cfu/g) of Escherichia coli strain (serotype O158:H23) subsequently stored at 8, 12, 16, 20 and 24 degrees C for 6h. A polynomial regression model for log difference (log(diff)) was developed at each inoculum level studied through the calculation of the effective static temperature (T(eff)). Furthermore, the developed model was integrated within a risk-based approach with real time/Temperature (t/T) data collected in three Spanish foodservice centers: school canteens, long-term care facilities (LTCF) and hospitals. Statistical distributions were fitted to t/T data and estimated log(diff) values were obtained as model outputs through a Monte Carlo simulation (10,000 iterations). The results obtained at static conditions indicated that the maintenance of the lettuce at 8 degrees C slightly reduced the E. coli population from -0.4 to -0.5 log cfu/g. However, if chill chain is not maintained, E. coli can grow up to 1.1 log cfu/g at temperatures above 16 degrees C, even at low contamination levels. Regarding log(diff) estimated in foodservice centers, very low risk was obtained (log(diff)<1.0 log cfu in all cases). Mean T(eff) values obtained in hospitals were the lowest ones (11.1 degrees C) and no growth of E. coli was predicted in >92% of simulated cases. The results presented in this study could serve food operators to set time/Temperature requirements for ready to-eat foods in foodservice centers, providing a scientific basis through the use of predictive modeling. These findings may also serve to food safety managers to better define the control measures to be adopted in foodservice centers in order to prevent food-borne infections. PMID- 22677606 TI - Quantitative study of viable Vibrio parahaemolyticus cells in raw seafood using propidium monoazide in combination with quantitative PCR. AB - In this study we developed a specific and sensitive quantitative PCR (qPCR) method combined with a propidium monoazide (PMA) sample treatment to quantify tdh positive viable cells of V. parahaemolyticus in raw seafood (PMA-qPCR). The high selectivity of primers and probes were demonstrated by using purified DNA from 57 strains belonging to 18 species. Using these primers and probes for qPCR and in artificial contamination samples, a good correlation was obtained between Ct values and log CFU/reaction in the range of 12-1.2*10(6)CFU/reaction both from qPCR and PMA-qPCR with R(2) values of 0.9973 and 0.9919, respectively. The optimization of PMA concentration showed that 8 MUg/mL was considered optimal to achieve a compromise between minimal impact on intact cells and maximal signal reduction in compromised cells. However, turbidity and cell concentration experiments showed that PMA treatment was not effective in samples where turbidities were >=10 NTU and OD(600 nm) values were >=0.8. PMA-qPCR was compared with culture isolation and traditional qPCR in environmental samples (including oyster, scallop, shrimp, and crab). The PMA-qPCR resulted in lower numbers of log CFUg(-1) than qPCR, with values having better agreement with numbers determined by culture isolation. In conclusion, this method is an effective tool for producing reliable quantitative data on viable V. parahaemolyticus in raw seafood. PMID- 22677607 TI - Ultrafiltration improves ELISA and Endopep MS analysis of botulinum neurotoxin type A in drinking water. AB - The objective of this study was to adapt and evaluate two in vitro botulinum neurotoxin (BoNT) detection methods, including the Botulinum Toxin ELISA and the Endopep MS (a mass spectrometric-based endopeptidase method), for use with drinking water samples. The method detection limits (MDL) of the ELISA and Endopep MS were 260 pg/mL and 21 pg/mL of BoNT/A complex toxin, respectively. Since toxin could be present in water samples at highly dilute concentrations, large volume (100-L) samples of municipal tap water from five US municipalities having distinct water compositions were dechlorinated, spiked with 5 MUg BoNT/A, and subjected to tangential-flow ultrafiltration (UF) using hollow fiber dialyzers. The recovery efficiency of BoNT/A using UF and quantified by ELISA ranged from 11% to 36% while efficiencies quantified by MS ranged from 26% to 55%. BoNT/A was shown to be stable in dechlorinated municipal tap water stored at 4 degrees C for up to four weeks. In addition, toxin present in UF-concentrated water samples was also shown to be stable at 4 degrees C for up to four weeks, allowing holding of samples prior to analysis. Finally, UF was used to concentrate a level of toxin (7 pg/mL) which is below the MDL for direct analysis by both ELISA and Endopep MS. Following UF, toxin was detectable in these samples using both in vitro analysis methods. These data demonstrate that UF concentration of toxin from large volume water samples followed by use of existing analytical methods for detection of BoNT/A can be used in support of a monitoring program for contaminants in drinking water. PMID- 22677608 TI - Zebrafish response to robotic fish: preference experiments on isolated individuals and small shoals. AB - Recently developed bioinspired robots imitate their live counterparts in both aspect and functionality. Nevertheless, whether these devices can be integrated within the ecological niche inspiring their design is seldom tested experimentally. An elemental research question concerns the feasibility of modulating spontaneous behaviour of animal systems through bioinspired robotics. The following study explores the possibility of engineering a robotic fish capable of influencing the behaviour of live zebrafish (Danio rerio) in a dichotomous preference test. While we observe that the preference for the robotic fish never exceeds the preference for a conspecific, our data show that the robot is successful in attracting both isolated individuals and small shoals and that such capability is influenced by its bioinspired features. In particular, we find that the robot's undulations enhance its degree of attractiveness, despite the noise inherent in the actuation system. This is the first experimental evidence that live zebrafish behaviour can be influenced by engineered robots. Such robotic platforms may constitute a valuable tool to investigate the bases of social behaviour and uncover the fundamental determinants of animal functions and dysfunctions. PMID- 22677609 TI - Rear-side localization of the centrosome in migrating neuroblastoma Neuro-2a cells and its roles in process elongation. AB - Axon elongation is usually performed by the migration of growth cones that leave axons. Axon microtubules are generated by enhanced polymerization of tubulin in the growth cones. Some kinds of neurons like cerebellar granule cells, however, generate axons as a result of migration of the cell body leaving axons at the rear. The mechanism to generate microtubules during such growth cone-independent elongation of axons is not well understood. To establish an experimental model to study this mechanism, we cultured neuroblastoma (Neuro-2a) cells on substrates that facilitate cell migration. When cultured on laminin-treated substrate, cells migrated actively and left processes at the rear. We investigated the role of the centrosome in this process formation. The centrosomes were always located at the base of the processes, i.e., at the rear side of the migrating cell body. Close observation of cytoskeletons revealed microtubules limited around the centrosomes, but concentrated at the periphery of the cells or within the processes. Microtubule regrowth experiments showed the ability of the centrosomes to nucleate microtubules. We thus examined the role of microtubule release from the centrosomes, by knocking down the expression of spastin, a microtubule severing enzyme. Introducing siRNA for spastin into Neuro-2a cells reduced both the migration speed and the length of the processes. Taken together, Neuro-2a cells on laminin proved useful as a model to study the alternative type of axon elongation in which cell migration leaves axons at the rear. This model provided evidence for the involvement of microtubule release from centrosomes in the mechanisms for this type of process elongation. PMID- 22677610 TI - Optimizing chimerism level through bone marrow transplantation and irradiation to induce long-term tolerance to composite tissue allotransplantation. PMID- 22677611 TI - Watch and wait: conservative management of lower gastrointestinal bleeding. AB - BACKGROUND: Although indications for surgery in lower gastrointestinal bleeding (LGIB) are widely described, practice varies. This study was designed to assess outcomes of patients allowed to exceed traditional triggers for surgery because of LGIB. METHODS: This is a retrospective review of patients at an urban tertiary hospital over a 3-y period that had LGIB necessitating (99m)Tc-labeled red blood cell scintigraphy. Traditional indications for operative treatment of LGIB were defined as transfusion of >6U of packed red blood cells, hemodynamic instability, bleeding lasting >72h, and rebleeding after cessation of bleeding for >24h. RESULTS: One hundred ninety-four LGIB patients had scintigraphy during the period of study with 180 meeting inclusion criteria. Fifty-six (31%) patients had at least one operative indication, and 32 (60%) were managed nonoperatively without a mortality. There were two (8.3%) mortalities in those who had operative management, one of which was because of exsanguination. Eighteen (32%) patients who met operative criteria were unlocalized. CONCLUSIONS: Patients with LGIB can be safely managed nonoperatively, even when the bleed is unlocalized and traditional indications for surgery are met. Exsanguinations because of LGIB treated nonoperatively are rare except in patients deemed not to be surgical candidates. PMID- 22677612 TI - Prophylactic retention sutures in midline laparotomy in high-risk patients for wound dehiscence: a randomized controlled trial. AB - BACKGROUND: Abdominal wound dehiscence (WD) is a postoperative complication with high mortality and morbidity rates. Retention sutures are often used in surgical take-back for dehiscence. The aim of this study was to assess the reduced rate of dehiscence in midline laparotomy using prophylactic retention sutures in high risk patients. MATERIALS AND METHODS: Three hundred high-risk patients with at least two risk factors for dehiscence who underwent midline laparotomy between 2008 and 2010 were randomly divided into two groups. In the control group, the fascia was continuously repaired using a running looped #1 nylon suture. For the intervention group, we added retention sutures that included the skin, subcutaneous tissue, rectus muscle, and abdominal fascia. We compared the rates of WD, evisceration, wound infection, postoperative pain, postdehiscence mortality, and late incisional hernia for these two groups. RESULTS: After accounting for early mortalities, 147 patients were followed in the intervention group and 148 patients in the control group. WD occurred in 6 patients (4%) in the intervention group and 20 control patients (13.3%) (P = 0.007). Abdominal evisceration after surgery occurred in 1 patient (0.7%) with retention sutures and 4 control patients (2.7%) (P = 0.371). There was no significant difference in wound infection and incisional hernia between the two groups. Postoperative pain scores between the two groups did not differ significantly during the first 3 d, but did differ on the fourth day. CONCLUSION: Prophylactic retention sutures reduce the occurrence of WD following midline laparotomy in high-risk patients with multiple risk factors for impaired wound healing without imposing remarkable postoperative complications. PMID- 22677613 TI - Increased activation of the transcription factor c-Jun by MAP kinases in monocytes of multiple trauma patients is associated with adverse outcome and mass transfusion. AB - BACKGROUND: Post-traumatic dysfunction of the immune system is a major source of morbidity and mortality in patients with multiple trauma. The underlying intracellular mechanisms are still incompletely understood. Previous mRNA expression studies in monocytes suggested an involvement of the MAP kinases p38 and JNK and of the transcription factor c-Jun. Therefore, it was the aim of this study to elucidate whether alterations in the protein expression p38 MAPK, JNK, and c-Jun could be linked to PRBC substitution and survival. MATERIALS AND METHODS: Thirty-seven patients with blunt multiple injuries and an ISS > 16 points were enrolled in our study. Blood was drawn on admission and 6, 12, 24, 48, and 72 h after the traumatic event. Monocytes were isolated immediately after sample collection and nuclear protein was extracted and phosphoprotein concentrations were measured. The resulting data were statistically analyzed. RESULTS: An increased activation of MAP kinases and c-Jun could be shown in patients who died from their injuries. Additionally, patients who received PRBC substitution >=10 units exhibited increased expression of activated MAP kinases and c-Jun. CONCLUSIONS: We present a serial, sequential investigation in human monocytes of major trauma patients evaluating the activation of p38 MAPK, JNK and c-Jun in the post-traumatic period. We show that death after trauma and massive PRBC substitution are associated with activation of this pathway. The p38 MAPK, JNK, and c-Jun have well established proinflammatory properties. Therefore, it appears likely that this pathway is involved in the systemic hyperinflammatory states seen after massive PRBC transfusion and multiple trauma. PMID- 22677614 TI - Impact of endotoxin measured by an endotoxin activity assay during liver transplantation. AB - BACKGROUND: Endotoxin (Et) in the portal vein blood is processed by the hepatic reticuloendothelial system. Thus, it is possible that the Et kinetics of the peripheral venous blood may be useful as a biological index that can be used to evaluate liver function. In this study, we measured Et using the endotoxin activity assay in peripheral venous blood during living donor liver transplantation (LDLT), to study its clinical significance. METHODS: Subjects were 17 patients who underwent LDLT. In the perioperative peripheral venous blood, was measured Et activity (EA) using the endotoxin activity assay at 1 or 2 d before LT, and then on 1, 5, 7, 14, and 21 postoperative days. RESULTS: Patients with infections had significantly higher EA levels compared with those without complications before LDLT and 14 postoperative days (P = 0.038 and 0.027, respectively). The average EA level of patients with infections and without complications before LT was 0.22 and 0.08, respectively (P = 0.038). Patients with an EA level higher than 0.20 before LDLT had a significantly longer period of hospitalization compared with those without complications (P = 0.038). CONCLUSIONS: A preoperative EA level more than 0.20 is a high risk factor for post-transplant infection and a prolonged period of hospitalization. PMID- 22677616 TI - Evaluation of compatibility and stability of filtered 99mTc-sulfur colloid when combined with fluorescent indocyanine green dye. AB - It is a common practice to administer dyes and radiopharmaceuticals separately for the localization of sentinel nodes in patients with biliary tract malignancies. The objective of this study was to evaluate the chemical properties and particle size of filtered (99m)Tc-sulfur colloid before and after it is combined with indocyanine green for injection. This study also evaluated the compatibility and stability of the two when combined, for the possibility of a single injection. METHODS: (99m)Tc-sulfur colloid was prepared according to the package insert, and the final preparation was passed through a sterile 0.2-MUm filter. Green dye was also prepared as per the package insert. In a sterile syringe, 0.25 mL of 14.8-MBq (400-MUCi) filtered (99m)Tc-sulfur colloid was mixed with 0.25 mL of 1.25-mg green dye in a 1:1 proportion for a total volume of 0.50 mL. The radiochemical purity and pH of filtered (99m)Tc-sulfur colloid were obtained immediately and at 1 and 2 h after preparation. Particle size was analyzed using an electron microscope immediately and at 2 h. RESULTS: The average radiochemical purity was 97.6% +/- 2.0% (n = 51). The average pH was 5.56 +/- 0.26 (n = 51). Evaluation of the particle size of filtered (99m)Tc-sulfur colloid with the green dye was determined by electron microscopy to be an average of 53 +/- 30 nm (n = 365) at 0 h and 60 +/- 35 nm (n = 303) at 2 h. This was compared with filtered (99m)Tc-sulfur colloid without the green dye, which averaged 71 +/- 41 nm (n = 41). Measurements of unfiltered (99m)Tc-sulfur colloid were recorded at 253 +/- 192 nm (n = 21) for additional comparisons. CONCLUSION: The chemical properties and particle size of filtered (99m)Tc-sulfur colloid were not affected by the addition of the green dye; thus, combination of filtered (99m)Tc-sulfur colloid and green dye in the same syringe for administration is suitable. PMID- 22677615 TI - Elevated systolic blood pressure after trauma: tolerated in the elderly. AB - BACKGROUND: We undertook the current study to determine the impact of elevated admission systolic blood pressure (SBP) on trauma patients without severe brain injury. MATERIALS AND METHODS: We conducted a retrospective review of the Los Angeles County Trauma System database to identify all patients with moderate to severe injuries (injury severity score >9) admitted between 2003 and 2008. Patients with head abbreviated injury score >3 were excluded. We divided the remaining patients into three age cohorts and conducted multivariate regression modeling at increasing SBP thresholds to identify independent predictors of mortality. RESULTS: A total of 23,931 patients met inclusion criteria. Overall mortality was 8.6% and it increased with age across the three groups. The admission SBP thresholds associated with significantly increased mortality in the young and middle-aged were >190 mm Hg (AOR 1.5, P = 0.04) and >180 mm Hg (AOR 1.5, P = 0.01), respectively. In the elderly, no admission SBP threshold was associated with significantly increased mortality. Interestingly, several elevated admission SBP thresholds were associated with significantly reduced mortality in the elderly (>150 mm Hg AOR 0.6, P < 0.01; >160 mm Hg AOR 0.6, P < 0.01; and >170 mm Hg AOR 0.7, P = 0.02). CONCLUSIONS: The admission SBP thresholds that predicted higher mortality for the young and middle-aged were >190 mm Hg and >180 mm Hg, respectively. Elderly trauma patients tolerated higher admission SBP than their younger counterparts and multiple elevated SBP thresholds were associated with significantly reduced mortality in the elderly. PMID- 22677617 TI - Individualized radiation dose control in 256-slice CT coronary angiography (CTCA) in retrospective ECG-triggered helical scans: using a measure of body size to adjust tube current selection. AB - PURPOSE: To reduce radiation dose for retrospective ECG-triggered helical 256 slice CTCA by determining an optimal body size index to prospectively adjust tube current. METHODS: 102 consecutive patients with suspected CAD underwent retrospective ECG-triggered CTCA using 256-slice CT scanner. Six body size indexes including BMI, nipple level (NL) bust, thoracic anteroposterior diameter at NL, chest circumference (CC) at NL, left main and right coronary artery (RCA) origin level were measured and their correlation with noise was evaluated using linear regression. An equation was developed to use this index to adjust tube current. Additional 102 consecutive patients were scanned with the index-based mAs adjustment. A t-test for independent samples was used to compare radiation dose levels with and without the index-based mAs selection method. RESULTS: Linear regression indicated that CC RCA had the best correlation with noise (R2=0.603). Effective radiation dose was reduced from 16.6+/-0.9 to 9.8+/-2.7 mSv (p<0.01), i.e. 40.9% lower dose with the CC RCA-adapted tube current method. The image quality scores indicated no significant difference with and without the size-based mAs selection method. CONCLUSION: An accessible measure of body size, such as CC RCA, can be used to adapt tube current for individualized radiation dose control. PMID- 22677618 TI - Evaluation of conventional Doppler fetal cardiac function parameters: E/A ratios, outflow tracts, and myocardial performance index. AB - Structural evaluation of the fetal heart is well established. Functional evaluation using pulsed-wave Doppler may also be performed. E/A ratios express the relationship between the maximal velocities of the E and A waveforms of ventricular filling. In normal fetuses, E/A ratios are usually <1 but show a constant increment during gestation, mainly related to the increment of the E wave. In intrauterine growth restriction (IUGR) fetuses, E/A ratios are lower compared to values in normally grown fetuses at the same gestational age. Cardiac outflows provide information on the time-velocity integral that, combined with the vessel area, allows calculation of the left and right cardiac outputs. In normal fetuses there is a predominance of the right ventricle (55-60%) in contributing to the combined cardiac output. In IUGR fetuses this predominance shifts to the left ventricle in order to increase the flow to the upper part of the fetal body and brain. The myocardial performance index (MPI) also provides information on systolic and diastolic cardiac function. The MPI is an early and consistent marker of cardiac dysfunction which becomes altered in early stages of chronic hypoxia or in cases with cardiac overload such as in twin-to-twin transfusion syndrome. PMID- 22677619 TI - Higher expression of the novel gene upregulated gene 4 in two acute lymphoblastic leukemia patients with poor prednisolone response. AB - Elucidation of the molecular mechanisms of leukemogenesis is important for a better understanding of the prognosis of acute lymphoblastic leukemia (ALL). Studies have shown that the expression of upregulated gene 4 (URG4), which promotes cell growth and survival, is increased in different types of carcinomas including hepatocellular carcinoma, gastric cancer and osteosarcoma. Similarly, higher expression of URG4 and cyclin D1 gene might promote proliferation of the blast cells by causing escape from the G1 checkpoint and entry into the S phase. This study reports the high expression level of URG4 in 2 high-risk ALL patients for the first time in the literature. In conclusion, the higher expression of URG4 in our 2 patients suggests that URG4 might be involved in leukemogenesis. Future studies with a large number of high-risk ALL patients and cell culture studies are needed to demonstrate the exact role of URG4 in leukemogenesis. PMID- 22677620 TI - Complex dynamic of dengue virus serotypes 2 and 3 in Cambodia following series of climate disasters. AB - The Dengue National Control Program was established in Cambodia in 2000 and has reported between 10,000 and 40,000 dengue cases per year with a case fatality rate ranging from 0.7 to 1.7. In this study 39 DENV-2 and 57 DENV-3 viruses isolated from patients between 2000 and 2008 were fully sequenced. Five DENV2 and four DENV3 distinct lineages with different dynamics were identified. Each lineage was characterized by the presence of specific mutations with no evidence of recombination. In both DENV-2 and DENV-3 the lineages present prior to 2003 were replaced after that date by unrelated lineages. After 2003, DENV-2 lineages D2-3 and D2-4 cocirculated until 2007 when they were almost completely replaced by a lineage D2-5 which emerged from D2-3 Conversely, all DENV-3 lineages remained, diversified and cocirculated with novel lineages emerging. Years 2006 and 2007 were marked by a high prevalence of DENV-3 and 2007 with a large dengue outbreak and a high proportion of patients with severe disease. Selective sweeps in DENV-1 and DENV-2 were linked to immunological escape to a predominately DENV 3-driven immunological response. The complex dynamic of dengue in Cambodia in the last ten years has been associated with a combination of stochastic climatic events, cocirculation, coevolution, adaptation to different vector populations, and with the human population immunological landscape. PMID- 22677621 TI - Prevalence and correlates of cognitive impairment in adults with subjective memory complaints in primary care centres. AB - AIMS: To examine the prevalence and correlates of cognitive impairment (CI) in adults over 50 years old attending primary care centres with complaints of memory failure. METHODS: A sample of 580 individuals aged 50+ years with no previous diagnosis of dementia was assessed by use of the Mini Mental State Examination, the Cambridge Cognitive Assessment-Revised and the California Verbal Learning Test - to evaluate CI-dependent variables - and administration of a questionnaire on memory complaints and other instruments - to measure correlates. RESULTS: The prevalence of CI was 46.20% and positive associations were found for age, gender, level of education, subjective memory complaints, instrumental activities of daily living, reading habits and frequency of leisure activities. In the logistic regression, modelled CI was associated with older age, gender (49.12% women, 39.66% men), instrumental activities of daily living, and reading habits. CONCLUSION: Almost half of the adults aged 50+ years attending primary care centres with subjective memory complaints were affected by CI. Early evaluation of cognitive functioning is essential to establish adequate preventive and intervention strategies. PMID- 22677622 TI - Anaphylaxis to peanut in a patient predominantly sensitized to Ara h 6. AB - Diagnosis of peanut allergy has improved thanks to component-resolved diagnostics. Peanut allergen component Ara h 2 is considered to indicate true peanut allergy. The component Ara h 6 is structurally similar to Ara h 2, but the diagnostic value of analyzing IgE antibodies to Ara h 6 is unclear. A boy sensitized (>=0.35 kU(A)/l) to Ara h 8 but not to Ara h 1, Ara h 2 and Ara h 3 was challenged with peanut and developed grade II anaphylaxis. In serum collected at the time of challenge a doubling of IgE to the peanut allergen extract was observed compared to allergy testing 9 months earlier. In contrast, IgE levels to Ara h 1, Ara h 2, Ara h 3 and to Ara h 8 were rather unchanged. After another 2 months, Ara h 6 was analyzed and revealed a level of 24 kU(A)/l whilst Ara h 2 was 0.12 kU(A)/l. We suggest that IgE sensitization to Ara h 6 caused the reaction and conclude that analyses of IgE levels to peanut and peanut components should be performed in connection with a challenge. Furthermore, levels to Ara h 2 below 0.35 kU(A)/l may still indicate a risk of severe reaction at the time of challenge since in rare cases, Ara h 6 IgE antibodies may be present without occurrence of IgE antibodies to Ara h 2. PMID- 22677623 TI - Top-cited articles in environmental sciences: merits and demerits of citation analysis. AB - The purpose of this study was to identify the top-cited articles published in environmental science journals listed in Journal Citation Reports (JCR). The Web of Science database was used to retrieve the top-cited articles having 500 or more total citations from their publication to 2010. The articles were analyzed with regard to institution and country of origin with five indicators including total number of top-cited articles, as well as independent, collaborative, first author, and corresponding author articles. Article life was also investigated for history of impact of articles. Results showed that 88 articles were cited more than 500 times. These articles appeared in 26 different journals, with 28% of all top-cited articles in Environmental Science & Technology, followed by Water Resources Research. The top-cited articles published since 1971 to 2002 were from 17 countries. The USA published the most of the articles and was ranked on top among the five indicators. The U.S. Geological Survey was the most productive institution while, the Brunel University, UK published the most inter institutionally collaborative and corresponding author articles under environmental science category. PMID- 22677624 TI - Prevalence and survival of potential pathogens in source-segregated green waste compost. AB - Composting of source-separated green waste (SSGW) is essential to meet the EU Landfill Directive target and agricultural land is considered a significant market for the resulting composts. A critical review of the literature was performed to evaluate the potential for pathogens to enter the composting process via SSGW feedstocks and the likelihood of their survival of the composting process and subsequent application to land. This is discussed in the context of application of other organic wastes to land. It was concluded that zoonoses such as verotoxigenic Escherichia coli and Salmonella spp. are unlikely to survive and effective composting process, whereas spore forming organisms are more resistant to composting but are also ubiquitous in the environment. Adherence to existing guidelines, such as those for farm yard manures, is likely to provide a rational degree of health protection for humans and livestock. PMID- 22677626 TI - Catalytic enzyme activity on a biosensor chip: combination of surface plasmon resonance and mass spectrometry. AB - Surface plasmon resonance (SPR) as a label-free biosensor technique has become an important tool in drug discovery campaigns during the last couple of years. For good assay performance, it is of high interest to verify the functional activity on the immobilization of the target protein on the chip. This study illustrates the verification of the catalytic activity of the drug target protein PqsD by monitoring substrate conversion as a decrease in SPR signal and product detection by ultra high-performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS(2)). This assay would be applicable to control surface activity of immobilized ligands. PMID- 22677625 TI - Synthesis of NaYF(4):Yb,Er/single-walled carbon nanohorns nanocomposite and its application as cells label. AB - A novel nanocomposite synthesis method of amino-modified NaYF(4):Yb,Er upconversion luminescent nanoparticles and single-walled carbon nanohorns was developed via covalent linkage for the first time. The nanocomposite was covalently coupled with rabbit anti-CEA8 antibody and then used successfully as a cell labeling agent for the immunolabeling and imaging of HeLa cells. PMID- 22677627 TI - Selective N-terminal fluorescent labeling of proteins using 4-chloro-7 nitrobenzofurazan: a method to distinguish protein N-terminal acetylation. AB - A fluorogenic derivatization method was developed to distinguish the protein N terminal acetylation status. The unacetylated protein selectively reacted with 4 chloro-7-nitrobenzofurazan (NBD-Cl) at neutral pH to provide high fluorescence. In contrast, the protein with N-terminal acetylation was essentially nonfluorescent under the same conditions despite the presence of many internal lysine residues. Fluorescence of the NBD-labeled protein was very stable, and only micromolar concentrations of proteins were required for reliable detection. This method also provides a general and practical way to quantify proteins when their N-terminal amino group is available. PMID- 22677628 TI - Decorrelation of sensory-evoked neuronal responses in rat barrel cortex during postnatal development. AB - The ability to detect and discriminate sensory stimuli greatly improves with age. To better understand the neural basis of perceptual development, we studied the postnatal development of sensory responses in cortical neurons. Specifically, we analyzed neuronal responses to single-whisker deflections in the posteromedial barrel subfield (PMBSF) of the rat primary somatosensory cortex. Responses of PMBSF neurons showed a long onset latency and duration in the first postnatal week, but became fast and transient over the next few weeks. Trial-by-trial variations of single neuron responses did not change systematically with age, whereas the covariation of responses across trials between neurons (noise correlation) was high on postnatal day 5-6 (P5-6), and gradually decreased with age to near zero by P30-31. Computational analyses showed that pooled responses of multiple neurons became more reliable across stimulus trials with age. The period over which these changes occurred corresponds to the period when rats develop a full set of exploratory whisking behavior. We suggest that reduced noise correlation across a population of neurons, in addition to sharpening the temporal characteristics of single neuron responses, may help improve behavioral performance. PMID- 22677629 TI - Use of the subjective global assessment to predict health-related quality of life in chronic kidney disease stage 5 patients on maintenance hemodialysis. AB - OBJECTIVE: The purpose of this study was to determine whether a subjective global assessment (SGA) score was predictive of health-related quality of life (HRQoL) in stage 5 chronic kidney disease patients on maintenance hemodialysis (MHD). DESIGN AND SETTING: This was a cross-sectional secondary data analysis of MHD patients receiving therapy 3 times a week at dialysis centers located in the United States, Canada, and New Zealand. Nutritional status was assessed using the 7-point SGA. HRQoL was determined using the Medical Outcomes Study 36-item Short Form (SF-36). RESULTS: The study sample consisted of 94 men (n = 47, 50%) and women (n = 47, 50%), with a mean age of 64.9 +/- 12.9 years. The mean SGA score at the end point of the study (6 months) was 5.8 +/- 1.1. Participants had a mean HRQoL physical health score of 36.5 +/- 9.3 at 6 months, indicating a worse physical health state. The HRQoL mental health summary score was within the normal range (50.5 +/- 11.1). After controlling for confounders in the hierarchical regression models, the SGA score significantly predicted HRQoL physical health (R(2) change = 0.124; P = .012). No association was found between the SGA score and HRQoL mental health (P = .925). CONCLUSIONS: The SGA score is a significant predictor of HRQoL physical health. Given that nutritional status impacts HRQoL and that decreased HRQoL in patients on MHD is associated with mortality, complications, and reduced compliance with treatment, using the SGA to measure nutritional status can be a tool to help identify dialysis patients with a lower HRQoL in terms of physical health. PMID- 22677630 TI - Dietary inorganic phosphorus regulates the intestinal peptide transporter PepT1. AB - BACKGROUND: Both organic and inorganic phosphorus (Pi) are present in regularly consumed foods, such as meats, eggs, and dairy products. Pi is often included in foods as an additive (as hidden phosphorus). The intestinal peptide transporter PepT1 mediates protein absorption, which is disturbed in renal insufficiency. Our aim was to determine the effects of dietary Pi content on the peptide transport activity and expression of PepT1. METHODS: The following animal models were used: (1) 7-week-old male Wistar rats; and (2) rats that underwent 3/4 nephrectomy to induce chronic kidney disease (CKD). The rats were fed a normal-protein (20%) diet containing low (0.02%), normal (0.6%), or high (1.2%) Pi levels. They were also fed diets containing varying amounts of protein and either low or normal Pi levels as follows: (1) low Pi/normal protein, (2) low Pi/high (50%) protein, (3) normal Pi/normal protein, and (4) normal Pi/high protein. RESULTS: Intestinal peptide transport activity and PepT1 expression levels were significantly higher in the CKD rats than in sham-operated control ones. Compared with the normal protein diet, the high-protein diet increased PepT1 expression in the CKD rats. Intestinal dipeptide transport activity and PepT1 protein levels did not increase in the rats fed the low-Pi/high-protein diet. In contrast, intestinal dipeptide transport activity and PepT1 protein expression were markedly increased in the rats fed the normal-Pi/high-protein diet. CONCLUSION: Dietary Pi levels regulate intestinal peptide transport activity through PepT1. PMID- 22677631 TI - Inflation and deflation timing of the AutoCAT 2 WAVE intra-aortic balloon pump using the autoPilot mode in a clinical setting. AB - The primary goal of this observational clinical study was to register the occurrence of incorrect inflation and deflation timing of an intra-aortic balloon pump in autoPilot mode. The secondary goal was to identify possible causes of incorrect timing. During IABP assistance of 60 patients, every four hours a strip was printed with the IABP frequency set to 1:2. Strips were examined for timing discrepancies beyond 40 ms from the dicrotic notch (inflation) and the end of the diastolic phase (deflation). In this way, 320 printed strips were examined. A total of 52 strips (16%) showed incorrect timing. On 24 of these strips, the incorrect timing was called incidental, as it showed on only one or a few beats. The other 28 cases of erroneous timing were called consistent, as more than 50% of the beats on the strip showed incorrect timing. We observed arrhythmia in 69% of all cases of incorrect timing. When timing was correct, arrhythmia was found on 13 (5%) of 268 strips. A poor quality electrocardiograph (ECG) signal showed on 37% of all strips with incorrect timing and 11% of all strips with proper timing. We conclude that inflation and deflation timing of the IABP is not always correct when using the autoPilot mode. The quality of the ECG input signal and the occurrence of arrhythmia appear to be related to erroneous timing. Switching from autoPilot mode to operator mode may not always prevent incorrect timing. PMID- 22677632 TI - The effects of zero-balance ultrafiltration on postoperative recovery after cardiopulmonary bypass: a meta-analysis of randomized controlled trials. AB - OBJECTIVE: Considered as a significant ultrafiltration technology during cardiopulmonary bypass (CPB), zero-balance ultrafiltration (Z-BUF) has always received controversial support regarding its effectiveness in reducing inflammatory mediators in plasma. Therefore, we conducted a meta-analysis to evaluate the clinical effect of Z-BUF through screening all relevant published randomized controlled trials (RCTs). METHODS: A comprehensive search was conducted to screen all RCTs of Z-BUF. Three trained investigators searched databases, including PubMed, Embase, the Cochrane Library, Google scholar, and Chinese literature databases (CNKI, WanFang, WeiPu). RCTs that compared Z-BUF with non-ultrafiltration were included. We focused on clinical outcomes such as length of stay in ICU, duration of ventilation, hospital stay, total amount of chest tube drainage and mortality. Finally, a total of 7 studies containing appropriate criteria were divided into an adult group and a pediatric group. A random effects model was used to calculate weighted mean difference with 95% confidence intervals. RESULTS: In the adult group, the benefits of Z-BUF in duration of ventilation (WMD=-2.77, 95% CI = [-6.26, 0.72], I(2)=71%, p=0.12) and the length of ICU stay (WMD=-4.13, 95% CI = [-10.09, 1.84], I(2)=77%, Z=1.36, p=0.17) were not apparent, with significant heterogeneity existing in the statistical results. The rest of the clinical parameters could not be evaluated due to insufficient data. In the pediatric group, combined analysis showed Z-BUF could reduce the duration of mechanical ventilation (WMD=3.07; 95%CI= [-7.56, 3.46], I(2)=17%, p=0.27). The advantage of Z-BUF was not observed in other clinical outcomes. CONCLUSION: The benefits of Z-BUF were not apparent, according to the report. Further studies involving combined ultrafiltration are expected to provide improved ultrafiltration during CPB. PMID- 22677633 TI - Review of exhaled nitric oxide in chronic obstructive pulmonary disease. AB - The up-regulation of nitric oxide (NO) by inflammatory cytokines and mediators in central and peripheral airway sites can be easily monitored in exhaled air (F(E)NO). It is now possible to estimate the predominant airway site of increased F(E)NO i.e. large versus peripheral airway/alveoli, and its potential pathologic and physiologic role in obstructive lung disease. In asthma, six double-blind, randomized, controlled algorithm trials have reported only equivocal benefits of add-on measurements of F(E)NO to usual clinical guideline management including spirometry. Significant design issues, as emphasized by Gibson, may exist. However, meta-analysis of these six studies (Petsky et al 2012 Thorax 67 199-208) concluded that routine serial measurements of F(E)NO for clinical asthma management does not appear warranted. In COPD including chronic bronchitis and emphysema, despite significant expiratory airflow limitation, when clinically stable as well as during exacerbation, F(E)NO, j'(awNO) and C(ANO) may all be normal or increased. Furthermore, the role of add-on monitoring of exhaled NO to GOLD management guidelines is less clear because of the absence of conclusive doubleblind, randomized, control trial studies concerning potential clinical benefits in the management of COPD. PMID- 22677634 TI - Measuring impact in stereotactic and functional neurosurgery: an analysis of the top 100 most highly cited works and the citation classics in the field. AB - BACKGROUND: Functional neurosurgery is a rapidly expanding field, with an exponentially growing literature. However, as with other fields, it can sometimes be difficult to distinguish between what is incremental and what is transformational. One way of measuring durable impact is examining the number of times a specific piece of scholarship is cited by others in the field. For example, papers that have been cited at least 400 times are designated 'citation classics' or works that, by virtue of very high citations, have been deemed of particular importance by researchers working in related disciplines. METHODS: We queried a large, web-based scholarly database using 49 pre-selected search terms. The results for each individual query was manually examined for relevance to the functional neurosurgery field in order to arrive at the top 100 most highly cited papers as well as the citation classics. RESULTS: The top 100 most cited papers, including 61 citation classics, in the stereotactic and functional neurosurgery field can be divided into 7 categories: functional/anatomic studies, technological innovations, and papers relevant to movement disorders, pain, psychiatry, radiosurgery and epilepsy. CONCLUSIONS: We have attempted to ascertain which papers have had, and continue to have, significant impact in our rapidly advancing field. At a minimum, the citation classics in functional neurosurgery provide both trainees and seasoned surgeons with a reading list of the 'must-know' works in the field - works whose influence have helped shape the direction of functional neurosurgery well into the future. PMID- 22677635 TI - Outcomes of repeat endothelial keratoplasty in patients with failed Descemet stripping endothelial keratoplasty. AB - PURPOSE: To report the outcomes of repeat endothelial keratoplasty (EK) in patients with failed Descemet stripping endothelial keratoplasty (DSEK). METHODS: The clinical records of patients with failed DSEK who underwent repeat EK surgery at a single institution were reviewed. RESULTS: A total of 20 eyes of 20 patients (8 men and 12 women) were included. The mean age at initial DSEK surgery was 69.9 +/- 11.9 years (range, 41-83 years). The causes of DSEK failure included progressive endothelial failure (8 eyes; 40%), primary graft failure (8 eyes; 40%), and endothelial rejection (4 eyes; 20%). The mean duration from primary DSEK to repeat EK was 13.1 +/- 10.3 months (range, 2-33 months). Removal of the failed DSEK donor disc was performed in all eyes. Mean preoperative corrected distance visual acuity (logMAR) before repeat EK surgery was 1.76, and this improved to 0.5 (P < 0.001) at the final follow-up at 27 months. Three eyes had limited corrected distance visual acuity secondary to ocular comorbidities (age related macular degeneration and advanced glaucomatous optic neuropathy). CONCLUSIONS: Repeat EK in patients with DSEK failure is an effective treatment modality. This is the preferred management option compared with penetrating keratoplasty because the advantages of EK surgery are maintained with repeat EK surgery. PMID- 22677636 TI - Stromal rejection following deep anterior lamellar keratoplasty: implications for postoperative care. AB - PURPOSE: To better characterize stromal rejection in the context of deep anterior lamellar keratoplasty (DALK) to improve early diagnosis and proper management. METHODS: The clinical records of 22 patients undergoing DALK by 2 surgeons between October 2006 and January 2008 were reviewed to identify patients who experienced stromal rejection. The diagnosis was made after the demonstration of acute stromal edema and/or stromal neovascularization in the absence of confounding preoperative conditions, such as herpetic keratitis. The incidence and clinical features of stromal rejection were compared with other descriptions found in the literature. RESULTS: Five of 20 eligible patients experienced stromal rejection within 12 months. Two patients were on low-dose corticosteroids when diagnosed. Four of the 5 patients were treated aggressively with q1-3 hourly prednisolone acetate 1% eye drops. The fifth was treated less aggressively with a maximum dose of only q6 hourly prednisolone acetate 1% and subsequently experienced a second rejection episode less than 5 months later. All episodes resolved completely with treatment. CONCLUSIONS: The incidence of stromal rejection in DALK is clinically significant, suggesting that these patients may benefit from corticosteroid regimens similar to those used in penetrating keratoplasty and implies that stromal rejection may be more common in penetrating keratoplasty than previously reported. If misdiagnosed or left untreated, stromal rejection can compromise graft clarity but prompt recognition and aggressive treatment can result in good anatomic and visual outcomes. PMID- 22677637 TI - Activated macrophages induce neovascularization through upregulation of MMP-9 and VEGF in rat corneas. AB - PURPOSE: To explore the mechanisms of activated macrophages (A-Mphi) involved in corneal angiogenesis. METHODS: Activated macrophages were elicited by mineral oil lumbar injection and implanted into corneal micropockets in rats for the treatment group, A-Mphi, and phosphate-buffered saline group as control. Corneal changes were observed with a slit lamp microscope, and histopathological features were evaluated by immunofluorescence. Reverse transcription-polymerase chain reaction was used to detect the relative expression of angiogenesis-associated factors and inflammatory mediators in the activated macrophages and corneal tissue after implantation. RESULTS: Immunofluorescence showed that peritoneal cells expressed antigens of cluster of differentiation 68 (CD68, ED1), matrix metalloproteinases-9 (MMP-9), and vascular endothelial growth factor (VEGF). Activated macrophages significantly induced corneal neovascularization (CNV), which peaked on day 5, whereas the control group and normal corneas showed less CNV. The activated macrophages and corneal tissue after implantation expressed the angiogenesis-related factors, such as cyclooxygenase-2, platelet-derived growth factor, transforming growth factor beta, interleukin-1 alpha, MMP-9, and VEGF in messenger RNA (mRNA). However, mRNA expression of MMP-9 and VEGF differed significantly only in the cornea between the A-Mphi group and phosphate-buffered saline group 5 days after the implantation. MMP-9 and VEGF expression of mRNA and protein was higher in the A-Mphi group than that in the control group and normal corneas. CONCLUSIONS: Activated macrophages induce obvious CNV and related mechanisms, which may be correlated with MMP-9 and VEGF autocrine in activated macrophages and upregulation of MMP-9 and VEGF in corneal tissue. PMID- 22677638 TI - "Triple-TEN" in the treatment of acute ocular complications from toxic epidermal necrolysis. AB - PURPOSE: Toxic epidermal necrolysis (TEN) is a devastating form of Stevens Johnson syndrome (SJS) with acute and chronic ocular complications. We present a novel aggressive combination strategy, termed "Triple-TEN", for the management of acute ocular TEN designed to minimize the risk of chronic, blinding sequelae. METHODS: Two patients with life-threatening TEN accompanied by severe ocular surface defects and fulminant symblephara formation underwent "Triple-TEN" management of their acute ocular disease under aseptic techniques in the critical care setting, after failed treatment with intensive topical therapy and surgical division of symblephara. The Triple-TEN protocol comprises (1) subconjunctival triamcinolone (Kenalog 20 mg) administered into each of the fornices to curb the local inflammatory response without compromising systemic immunity, (2) placement of amniotic membrane tissue mounted on a polycarbonate skirt (ProKera) over the corneal and limbal regions to facilitate reepithelialization of the ocular surface, and (3) insertion of a steeply curved acrylic scleral shell spacer (Technovent, SC21) to vault the lids away from the globe providing a barrier to symblephara formation. RESULTS: In both cases, ocular surface inflammation resolved within 4 weeks with no progression of conjunctival cicatrization or evidence of limbal epithelial stem cell failure at 1 year follow-up. There were no long-term complications of the Triple-TEN regimen. CONCLUSIONS: Aggressive treatment with the Triple-TEN protocol for acute ocular TEN resistant to first line therapy, may help prevent long-term blinding sequelae. PMID- 22677639 TI - Effect of glucocorticoid (triamcinolone acetonide) pretreatment in a murine penetrating keratoplasty and suture model. AB - PURPOSE: To evaluate the effect of glucocorticoid (triamcinolone acetonide injectable suspension) pretreatment on corneal neovascularization, lymphangiogenesis, and inflammation in a murine penetrating keratoplasty (PK) and corneal suture model. METHODS: For the PK model, BALB/c mice were used as recipients and C57BL/6 mice were used as donors. A group pretreated with subconjunctival glucocorticoid and a combination of post-subconjunctival and topical glucocorticoids (group I) was compared with two groups that did not receive glucocorticoid pretreatment [one group received a combination of subconjunctival and topical glucocorticoids postoperatively (group II) and the other group received only topical glucocorticoid treatment postoperatively (group III)]. All groups were treated with subconjunctival glucocorticoid on the day of surgery. For the corneal suture model, BALB/c mice were used. A group receiving only pre-suture glucocorticoid treatment (group A) and a group receiving only post-suture glucocorticoid treatment (group C) were compared with a control group that did not receive glucocorticoid therapy (group B). The degree of neovascularization, lymphangiogenesis, and inflammatory infiltration was compared in each of these models. RESULTS: In the PK model, the group receiving glucocorticoid pretreatment (group I) showed less neovascularization compared with the posttreatment-only groups (group II, P=0.043; group III, P=0.020) and less lymphangiogenesis compared with group III (P=0.005). In the corneal suture model, the glucocorticoid pretreatment group showed a similar level of neovascularization, lymphangiogenesis, and inflammatory infiltration as the posttreatment-only groups (P>0.05). CONCLUSIONS: Glucocorticoid pretreatment before PK decreases neovascularization and lymphangiogenesis compared with posttransplant glucocorticoid treatment alone. PMID- 22677640 TI - Novel noncontact meibography with anterior segment optical coherence tomography: Hosik meibography. AB - PURPOSE: To present a novel noncontact meibography system with anterior segment optical coherence tomography (OCT), which is widely used in clinics for the anterior segment (cornea, anterior chamber angle, etc.), and compare the results with preexisting infrared meibography. METHODS: This research was carried out at the Seoul St Mary's Hospital with 2 volunteers. Preexisting infrared meibography was performed on the subjects, and photographs of the meibomian gland were taken again with the anterior segment OCT. With the anterior segment OCT, a tomogram of the meibomian gland could be taken and a picture of the whole meibomian gland could be taken from the infrared images for monitoring. RESULTS: The resolution of the preexisting infrared meibography was a pixel size of 640 * 480. In the anterior segment OCT, the meibomian glands were clearly identified just beneath the palpebral conjunctiva. There was no problem in grading the meibomian gland with the infrared images for monitoring. The resolution was 239 * 178 or 129 * 95 pixels, depending on the save option of the photograph. CONCLUSIONS: This novel meibography using anterior OCT yielded meibomian gland tomograms without any additional equipment, and overall infrared meibography was possible for grading. We believe this new technique will be useful in clinics for meibomian gland dysfunction and the like. PMID- 22677641 TI - Descemet stripping automated endothelial keratoplasty performed by cornea fellows. AB - PURPOSE: To evaluate the outcomes of Descemet stripping automated endothelial keratoplasty (DSAEK) in 78 eyes with corneal endothelial dysfunction performed by cornea fellows under the supervision of experienced faculty members in an academic hospital. METHODS: In this interventional case series, 78 eyes of 73 patients with corneal endothelial dysfunction of different underlying etiologies were enrolled for DSAEK. Healthy donor corneas with more than 2000 endothelial cells per square millimeter were requested. Intraoperative and postoperative complications were recorded. Best-corrected visual acuity, postoperative refraction, central corneal thickness, and endothelial cell density at 6 months after surgery were also registered and analyzed. RESULTS: Among 78 eyes of 73 patients with corneal endothelial dysfunction, DSAEK was performed on 55 eyes (70.5%) due to pseudophakic bullous keratopathy, which was the most common indication. Other indications included aphakic bullous keratopathy in 6 (7.7%), Fuchs endothelial dystrophy in 7 (8.9%), failed penetrating keratoplasty in 5 (6.4%), failed DSAEK in 3 (3.8%), and congenital hereditary endothelial dystrophy in 2 eyes (2.6%). All operations were performed by 4 cornea fellows supervised by the faculty members. Mean preoperative best-corrected visual acuity was 1.8 LogMAR, which improved to 0.77 LogMAR 6 months after the surgery. At this time, the mean central corneal thickness was 709.09 +/- 109.24 MUm and mean 6-month postoperative endothelial cell density was 1180 cells per square millimeter representing a mean cell loss of 61%, and mean spherical equivalent was +0.53 +/- 1.83 diopter. Lenticule detachment was observed in 17 eyes (21.8%). Graft failure occurred in 8 eyes (10.2%). CONCLUSIONS: Outcomes of DSAEK performed by cornea fellows supervised by the faculty members seems to be fairly acceptable. PMID- 22677642 TI - Biomechanical evaluation of cornea in topographically normal relatives of patients with keratoconus. AB - PURPOSE: To compare the biomechanical properties of the cornea between topographically normal relatives of patients with keratoconus and age-matched controls. METHODS: Thirty healthy individuals (control group) and 30 topographically normal relatives of patients with keratoconus (study group) were enrolled in this prospective, cross-sectional comparative study. Topographical measurements including pachymetric values, keratometry values, irregularity, and inferior-superior dioptric asymmetry difference values in the right eye of each participant were obtained using Orbscan II (Bausch & Lomb Laboratories, Inc, Rochester, NY). Corneal hysteresis (CH), corneal resistance factor (CRF), corneal compensated intraocular pressure, and Goldmann-related intraocular pressure were also measured using the Reichert Ocular Response Analyzer (ORA). RESULTS: Topographic parameters were not significantly different between both groups (P > 0.05). Mean CH was 9.9 +/- 1.6 mm Hg in the study group and 11.3 +/- 1.0 mm Hg in the control group (P = 0.001); mean CRF was 9.8 +/- 1.6 mm Hg and 11.2 +/- 2.1 mm Hg in the study and control groups, respectively (P = 0.013). Mean Goldmann related intraocular pressure was 15.0 +/- 4.3 mm Hg in the study group and 15.8 +/- 6.7 mm Hg in the control group (P = 0.603); mean corneal compensated intraocular pressure was 16.2 +/- 4.7 mm Hg in the study group and 15.4 +/- 5.8 mm Hg in the control group (P = 0.595). CONCLUSIONS: The CH and CRF values were significantly lower in the relatives of patients with keratoconus than in the controls. Future studies including monitoring of these participants with topographical and biomechanical measurements may indicate the role of this study in detection of early corneal changes in relatives of patients with keratoconus. PMID- 22677643 TI - The effect of topical pranoprofen 0.1% on the clinical evaluation and conjunctival HLA-DR expression in dry eyes. AB - PURPOSE: To investigate the effect of topical pranoprofen 0.1% on the clinical evaluation and conjunctival human leukocyte antigen II (HLA-DR) expression in dry eyes. METHODS: Sixty patients with dry eyes were randomized to 2 groups. Patients in group 1 received topical pranoprofen 0.1% plus topical sodium hyaluronate 0.1%; and patients in group 2 received sodium hyaluronate without pranoprofen. Ocular surface disease index (OSDI), tear film break-up time (TBUT), Schirmer I test, ocular surface staining (OSS), and conjunctival HLA-DR expression were evaluated before treatment and at 15 and 30 days after treatment. RESULTS: On day 15, patients in group 1 had significantly lower OSDI, OSS, and HLA-DR-positive cells compared with patients in group 2 (P < 0.01), and the TBUT was significantly longer in patients in group 1 than that of patients in group 2 (P < 0.01). On day 30, the difference between the 2 groups in OSS lost significance; however, there continued to be significant differences in the OSDI, TBUT, and HLA-DR expression between the 2 groups (P < 0.01). On days 15 and 30, the values in group 1 patients had significant improvement compared with their baseline values in terms of the above-mentioned parameters. The comparisons within group 2 did not reveal any significant differences. There was no significant effect in the Schirmer I test value in eyes of patients in group 1 or group 2 at days 15 or 30 (P > 0.05). CONCLUSIONS: Topical pranoprofen 0.1% has a beneficial effect in reducing the ocular signs and symptoms of dry eyes and decreasing the inflammatory markers of conjunctival epithelial cells. PMID- 22677644 TI - Complications from the placement of a tension-free suburethral sling using the transobturator and retropubic methods for treatment of female urinary incontinence. AB - OBJECTIVE: The aim of our study was to retrospectively analyze surgical complications arising from the collocation of suburethral mesh in the lower urinary tract, using both the transobturator and retropubic methods. PATIENTS AND METHODS: During the period between November 2002 and June 2011, we retrospectively studied 190 patients that were treated for stress urinary incontinence using a tension-free suburethral sling. 50 patients were treated using the retropubic route (SPARC(r)), and 140 patients were treated using a transobturator (MONARC(r)). RESULTS: In total, 16.57% of the patients presented with intraoperative, immediate postoperative or later postoperative complications. We observed a higher rate of complications with patients who were operated on retropubically (26%) than with patients who were operated on using the transobturator method (12%). CONCLUSIONS: The rate of complications for our study was low, and was even lower in the case of transobturator tape. Thus, we usually used transobturator tape in the treatment of stress incontinence. PMID- 22677647 TI - Effect of local environment, fibrin, and basic fibroblast growth factor incorporation on a canine autologous model of bioengineered cartilage tissue. AB - We developed a technique to form a bioabsorbable synthetic polymer (polyglycolic acid, PGA) combined with a natural polymer (fibrin) to serve as a scaffold to help retain seeded cells and improve the seeding efficiency of chondrocytes in an implantable construct. This approach was evaluated in a canine autologous implant model of bioengineered cartilage. The implantation site (subcutaneous or intrafascial) and the use of basic fibroblast growth factor (b-FGF) were also evaluated with this system. The intrafascial implantation site yielded optimal results, especially when used in conjunction with fibrin and a b-FGF sustained release system incorporated into the complex. A thicker, more sustained cartilagenous layer was formed, with a more vascularized outer fibrous supporting tissue layer. This combined approach of implant environment selection, natural polymer for cell retention, and growth factor supplementation offers a more optimized method for generating bioengineered auricular cartilage. PMID- 22677645 TI - Sphingolipid content of human adipose tissue: relationship to adiponectin and insulin resistance. AB - Ceramides (Cer) are implicated in obesity-associated skeletal muscle and perhaps adipocyte insulin resistance. We examined whether the sphingolipid content of human subcutaneous adipose tissue and plasma varies by obesity and sex as well as the relationship between ceramide content and metabolic indices. Abdominal subcutaneous adipose biopsies were performed on 12 lean adults (males = 6), 12 obese adults (males = 6) for measurement of sphingolipid content and activity of the main ceramide metabolism enzymes. Blood was sampled for glucose, insulin (to calculate homeostasis model assessment-estimated insulin resistance (HOMA(IR))) adiponectin, and interleukin-6 (IL-6) concentrations. Compared to lean controls, total ceramide content (pg/adipocyte) was increased by 31% (P < 0.05) and 34% (P < 0.05) in obese females and males, respectively. In adipocytes from obese adults sphingosine, sphinganine, sphingosine-1-phosphate, C14-Cer, C16-Cer, and C24-Cer were all increased. C18:1-Cer was increased in obese males and C24:1-Cer in obese females. For women only, there was a negative correlation between C16-Cer ceramide and plasma adiponectin (r = -0.77, P = 0.003) and a positive correlation between total ceramide content and HOMA(IR) (r = 0.74, P = 0.006). For men only there were significant (at least P < 0.05), positive correlations between adipocyte Cer-containing saturated fatty acid and plasma IL-6 concentration. We conclude that the sexual dimorphism in adipose tissue behavior in humans extends to adipose tissue sphingolipid content its association with adiponectin, IL-6 and insulin resistance. PMID- 22677648 TI - Construction of supramolecular helical nanofibers using renewable biomaterials: self-assembly of a cytidylic acid-appended bolaamphiphile in lemon juice. AB - We performed the self-assembly of a 1,18-cytidylic acid-appended bolaamphiphile (C18C) in lemon juice, which contained citric acid, and succeeded in forming left handed helical nanofibers with diameters, lengths, and pitches of ca. 6-7 nm, several hundred nm to 5 MUm, and ca. 30-40 nm, respectively. PMID- 22677650 TI - An improved LC-S/MS method for the quantitation of adenosine concentration in mice brain microdialysates. AB - A sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the determination of adenosine concentrations in mouse brain microdialysis samples was developed. High method sensitivity (LLOQ of 1.25 fmol) was achieved by on-line switching column. A C18 was employed as enrichment column and a cyano based (CN-SB) as analytical column. The method was fully validated for its sensitivity, selectivity, matrix effect and stability. It was successfully applied to measure quantitatively adenosine in brain of freely moving mice after different stimuli. PMID- 22677649 TI - Utility of routine ultrasound after laparoscopic cholecystectomy to detect early postoperative complication. AB - BACKGROUND AND AIM: In up to 3% of laparoscopic cholecystectomies, procedure related complications occur. Routine postoperative ultrasound is one means of screening for these complications. The aim of this study was to determine the utility of this practice after laparoscopic cholecystectomy. METHODS: A series of consecutive patients (n = 1,044) undergoing laparoscopic cholecystectomy from January 2007 to January 2011 was analysed. Primary endpoint was the detection of procedure-related complications by routine ultrasound. RESULTS: Routine ultrasound within the first 48 h after laparoscopic cholecystectomy was performed in 967 of 1,044 patients. Overall, 25 (2.4%) of the 1,044 patients suffered from procedure-related complications, but only in 2 patients was the complication detected by routine ultrasound. Findings were false-positive in 103 patients. This corresponds to a sensitivity of 8% and a specificity of 89%. Hospital stay was prolonged in the false-positive group. CONCLUSION: Routine postoperative ultrasound has a low sensitivity for the detection of complications after laparoscopic cholecystectomy. In almost all cases, the diagnosis is initiated by clinical findings. Therefore, routine ultrasound is of limited value in screening for postoperative complications after cholecystectomy. PMID- 22677651 TI - Development, validation and comparison of two microextraction techniques for the rapid and sensitive determination of pregabalin in urine and pharmaceutical formulations after ethyl chloroformate derivatization followed by gas chromatography-mass spectrometric analysis. AB - The present article reports first time the use of solid-phase microextraction (SPME) and dispersive liquid-liquid microextraction (DLLME) to extract pregabalin (PRG) from urine and pharmaceutical formulations followed by GC-MS analysis after ethyl chloroformate (ECF) derivatization. PRG is an antiepileptic and analgesic drug, which is a structural analogue of gamma-amino-butyric acid (GABA). It is approved by Food and Drug Administration (FDA) for the treatment of central nervous system (CNS) disorders and neuropathic pain. Initially PRG was derivatized with ECF in the presence of pyridine at room temperature for 30s. Experimental parameters were investigated for derivatization, SPME and DLLME conditions. The limit of detection (LOD) and limit of quantitation (LOQ) were found to be 0.019 MUg/ml and 0.063 MUg/ml for SPME and 0.022 MUg/ml and 0.075 MUg/ml for DLLME respectively. The percentage recovery, in case of SPME was in the range of 83-98% while for DLLME it is in the range of 84-98%. The intra and inter-day precisions were found to be less than 6%. The developed methods after ECF derivatization were found to be simple, fast, efficient and inexpensive. DLLME has several advantages like lesser extraction time and cost effectiveness as compared to SPME. The developed methods may find wide application for the routine determination of PRG in biological as well as in quality control samples of pharmaceutical formulations. PMID- 22677652 TI - Chemical crosslinking and mass spectrometric identification of interaction sites within soluble aggregate of protein therapeutics. AB - Protein aggregation presents a major challenge to bioengineering. In the present study, chemical crosslinking and mass spectrometry are employed to probe the interaction amongst soluble oligomer formed by Fc molecule of monoclonal antibody. Aggregation was induced by thermal stress at 42 degrees C for 6h under physiological pH. Contacting residues on adjacent molecules were captured with bifunctional crosslinker BS3, followed by mass spectrometric identification of the crosslinked sites. The approach provides site-specific information regarding the binding interface that would have broad application in the field. PMID- 22677653 TI - Determination of imatinib mesylate and related compounds by field amplified sample stacking with large volume sample injection capillary electrophoresis. AB - Imatimib mesylate is a drug for the treatment of gastrointestinal stroma tumor and chronic myelogenous leukemia. In this study, capillary electrophoretic analysis of imatinib mesylate and related compounds was developed. The optimized separation condition was NaH(2)PO(4) (10 mM) aqueous solution containing 5 mM of 2-hydroxypropyl-beta-cyclodextrin at a pH of 2.0. The separation could be obtained in less than 20 min when the separation voltage was 20 kV. To enhance the sensitivity, field amplified sample stacking combining with large volume sample injection was adopted. The optimal injection conditions were obtained by using methanol containing 0.5 mM HCl as the sample dilution solution and performing injection at a voltage of 15 kV for 60 s. The linearity ranges of ima amine, N-desmethyl imatinib and imatinib mesylate were 0.005-0.500 MUg/ml, and 4 chloromethyl-N-(4-methyl-3-((4-(pyridin-3-yl) pyrimidin-2-yl) amino) phenyl) benzamide was 0.010-0.500 MUg/ml, with good linear correlation coefficients (r(2)>0.9900). The intra-day and inter-day relative standard deviations of peak areas were satisfactory. Under the optimized condition, five batches of the synthesized samples were detected and ima amine was found in all the batches. Due to its simplicity, effectiveness and low price, the developed method can be used for quality control analysis of imatinib mesylate. PMID- 22677654 TI - HPLC-APCI-MS/MS method for the determination of catalpol in rat plasma and cerebrospinal fluid: application to an in vivo pharmacokinetic study. AB - Catalpol is a Chinese herb ingredient with potential for the treatment of neurodegenerative disorders. A high-performance liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry (HPLC-APCI-MS/MS) method was developed and validated to investigate the pharmacokinetics and biodistribution of catalpol in both the plasma and cerebrospinal fluid (CSF) of rats. Methanol was used to precipitate the protein from the biosamples, and the supernatant was collected for the assay. A Diamonsil C18 column (150 mm * 4.6 mm, 5 MUm) with a mobile phase of methanol-ammonium acetate (20 mM) (50:50, v/v), a 0.6 mL/min flow rate and a total run time of 3 min was used to separate catalpol and aucubin (internal standard, IS). A triple-quadrupole tandem mass spectrometer with an atmospheric pressure chemical ionization (APCI) source in the positive ion mode was operated in the multiple reaction-monitoring (MRM) mode to determine the concentration of catalpol at m/z 380.0-165.0 and that of IS at m/z 364.0 148.9. The linear range was 10-50000 ng/mL for plasma samples and 20-5000 ng/mL for CSF samples. At both the lower limit of quantification (LLOQ) and three levels QC (quality control) concentrations, the RSD was less than 12.9%, and the bias was -10.0% to 7.1%. The extraction recoveries for catalpol ranged from 72.9% to 109.5% from both rat plasma and CSF. The catalpol was administered to rats in 6 mg/kg doses via intravenous (i.v.) injection, and the pharmacokinetics and biodistribution studies were performed in both plasma and CSF. The results demonstrated that catalpol could be transported into the CSF via the AUC(CSF)/AUC(plasma) of 5.8% with a half-life (t(1/2)) of 1.5 h. Overall, the established HPLC-APCI-MS/MS method is rapid and sensitive, and has been successfully used to quantify catalpol in both plasma and CSF. PMID- 22677655 TI - Stereoselective analysis of endomorphin diastereomers: resolution of biologically active analogues by capillary electrophoresis applying cyclodextrins as mobile phase additives. AB - Seven diastereomer pairs of tetrapeptide analogues (TP) of endomorphin-1 and -2 were synthesized. A stereoselective capillary electrophoretic method was developed for controlling stereoisomeric ratio or purity. The isoelectric points of the tetrapeptides were between 8.3 and 8.9 as predicted and measured. A few of the analytes could be resolved without selectors due to the difference in their mobility. Neutral and anionic cyclodextrins (CDs) were applied in order to improve resolution. Stability constants as well as the mobilities of complexes were determined. Contributions of differences in the mobilities of free analytes and in the mobilities and stabilities of their complexes formed by CDs were equally important in the efficient resolution and migration order of diastereomers. As a result of the optimization of the pH of buffers and the concentration of the CD derivatives each diastereomer pair was resolved at baseline at least or better. PMID- 22677656 TI - Screening of new huprines--inhibitors of acetylcholinesterases by electrospray ionization ion trap mass spectrometry. AB - Acetylcholinesterase inhibitors (AChEI) are one of the drugs families validated for clinical use in the treatment of Alzheimer's disease (AD). For this reason, finding new more potent and more selective AChEIs is always of interest. Since 1961, the inhibitory activity of AChEI is evaluated through the Ellman's method. Herein, we reported a MS-based evaluation of potential new AChEI with the determination of their inhibitory activity (IC(50) and K(I)). Compared to the Ellman's method, that uses the substrate analog acetylthiocholine, the electrospray ionization ion trap mass spectrometry (ESI-IT-MS) consists in monitoring the conversion ratio of a low concentration of the natural substrate - acetylcholine to choline. We present here the inhibition activity of huprine X and six of its derivates (bearing different functional groups at position 9) towards the recombinant human (rhAChE) and Electrophorus electricus acetylcholinesterase (EelAChE). Mechanisms of action of selected inhibitors were evaluated by means of Lineweaver-Burk plot analysis. The Michaelis-Menten constants (K(M)), inhibitory constants (K(I)) were examined as well as the IC(50) to allow classifying a series of huprine derivatives by inhibition potency by a comparison with a reference (huprine X). Our results demonstrate that these drugs are very potent AChE inhibitors, especially (+/-)-huprine 6 with an inhibitory activity on recombinant human AChE (rhAChE) in the picomolar range. This study reveals the interest of huprine compounds in the treatment of AD. PMID- 22677658 TI - [Mental health of world's population: social and economic aspects (a literature review 2000-2010)]. AB - The authors had analyzed current approaches and results of the evaluation of the economic burden of mental health in the world derived from foreign research in 2000-2010. Sources of information were publications of the WHO database and the WHO regional offices, the database of the National Library of Medicine U.S. "MedLine", archives of publications by leading foreign medical journals in the field of mental health. The burden of mental illnesses, especially depression and anxiety disorders, has been increasing in all regions of the world. It has been shown that obtaining reliable estimates of mental health in modern conditions is only possible on the basis of reliable epidemiological, clinical and social/economic data which requires the development and improvement of mental health services as well as relevant social, public and private entities. PMID- 22677657 TI - Genioglossus fatigue in obstructive sleep apnea. AB - Obstructive sleep apnea (OSA) is a prevalent disorder that may cause cardiovascular disease and fatal traffic accidents but the pathophysiology remains incompletely understood. Increased fatigability of the genioglossus (the principal upper airway dilator muscle) might be important in OSA pathophysiology but the existing literature is uncertain. We hypothesized that the genioglossus in OSA subjects would fatigue more than in controls. In 9 OSA subjects and 9 controls during wakefulness we measured maximum voluntary tongue protrusion force (Tpmax). Using surface electromyography arrays we measured the rate of decline in muscle fiber conduction velocity (MFCV) during an isometric fatiguing contraction at 30% Tpmax. The rate of decline in MFCV provides an objective means of quantifying localized muscle fatigue. Linear regression analysis of individual subject data demonstrated a significantly greater decrease in MFCV in OSA subjects compared to control subjects (29.2 +/- 20.8% [mean +/- SD] versus 11.2 +/- 20.8%; p=0.04). These data support increased fatigability of the genioglossus muscle in OSA subjects which may be important in the pathophysiology of OSA. PMID- 22677659 TI - [Emotional and autonomous presentations of metabolic syndrome in childhood]. AB - We examined 46 children and adolescents, aged from 7 to 16 years, with metabolic syndrome (MS) and 20 healthy volunteers. Diagnosis was established by the presence of abdominal obesity. Total cholesterol, low density proteins, atherogenity index, blood insulin and glucose with the determination of insulin resistance index were measured. A special table suggested by A.M. Vein was used for assessment of autonomous tonus and reactivity, Kerdo index and Danini-Ashner reflex were calculated. Compensatory abilities in children with MS were determined by the results of variation cardiointervalography with the calculation of main indicators. The study of autonomous provision of activity was carried out using the experimental modeling of activity: mental, emotional. Emotions and personality were assessed by Shmishek-Leonhard questionnaire. The neurological examination did not reveal focal symptoms. The disintegration of the autonomous system activity manifested itself by the activation of ergotropic link accompanied by the changes in autonomous reactivity and formation of inadequate provision of activity. The results of psychological examination revealed the ecstatic type of accentuation that indicated high emotionality and psychological lability of subjects. PMID- 22677660 TI - [Psychopathological features and delusion of exaggerated self-esteem in endogenous manic-delusion states]. AB - Forty patients with endogenous manis-delusion states with the domination of exaggerated self-esteem in the clinical presentations were examined. Based on the analysis of mechanisms of delusion formation and congruency to the mania affect and its characteristics, 3 types of delusion syndromes have been singled out. Type 1 is characterized by the domination of delusion of exaggerated self-esteem, it is formatted by affective mechanisms as one of the symptoms of mania; type 2 is characterized by combined mechanisms of delusion formation (affective and acute delusion of sensuality - delusion of perception), with the domination of delusion of grandiosity congruent by its contest to mania affect. Type 3 is described by the formation of delusions according to mechanisms of acute paranoid state with paraphrenic-confabulatory modification congruent by the contest of affect to megalomaniac ideas of special mission, grandiosity, noble origin. All 3 types of manis-delusion states differed by characteristics of mania affect, plot characteristics and a degree of delusion scope as well as features of depersonalization. Diagnostic wrongfulness of the orientation only on the contest aspect of delusion and greater predictive value of mechanisms of delusion formation are discussed. PMID- 22677661 TI - [Balance of steroid hormones among children and teenagers with epilepsies]. AB - The level of steroid hormones (cortisol, cortisone, aldosterone) in children with epilepsy, aged from 4 to 18 years, was investigated. The levels of cortisol, cortisone and aldosterone were changed in 58.0%, 32.0% and 62.0% of patients with pharmacoresistant epilepsy, respectively, compared to age-matched controls. In case of epilepsy with positive effect of antiepileptic treatment, the changes of aldosterone were found only in 40.6% of patients. The level of hormones was, to a certain extent, age-dependent only in pharmacoresistant epilepsy. The greatest changes are registered in the following periods: at the age 4-7 years, the cortisone level corresponded to the norm in 33.3%, aldosterone in 44.4%; at the age 12-16 years, the indexes of cortisol corresponded to the norm in 26.7%, aldosterone in 20.0%; at the age 8 - 11 years, only the level of aldosterone was changed, it corresponded to the norm in 35.3% of cases. PMID- 22677663 TI - [Effect of mexidol on the development of the phenomenon of the neuronal excitotoxicity in vitro]. AB - Effect of mexidol on the development of the phenomenon of the excitotoxic syndrome in vitro has been studied. Mexidol inhibits in vitro the development of glutamate-induced neurotoxicity, ascorbate-dependent (non-enzymatic) and NADPH2 dependent (enzymatic) iron-induced lipid peroxide oxidation, is able in high concentrations to bind superoxide anion-radical, significantly increases the activity of Se-dependent glutathione peroxidase, decreases the activity of induced NO-synthase and does not impact on the activity of glutathione-SH transferase, catalase and neuronal NO-synthase. These effects underlie the antioxidant and antihypoxic action of the drug. PMID- 22677662 TI - [Experience in using xeomin in the treatment of arm and hand spasticity in the early rehabilitation phase of stroke]. AB - To reduce arm and hand spasticity, 28 patients in the early rehabilitation phase of ischemic hemisphere stroke received injections of the botulinum toxin A preparation xeomin in the content of complex rehabilitation programs. The following muscles: m. biceps brachii, m. flexor digitorum profundus, m. flexor digitorum superficialis, m. flexor carpi ulnaris, m. flexor carpi radialis were injected according to standard scheme. The total dose of drug was 200U in moderate (2-3 scores on the Ashworth scale) and 300U in marked (3-4 scores on the Ashworth scale) spasticity. Efficacy and safety of treatment was assessed at baseline and 2, 4, 8, 12, 16 weeks after injections. Xeomin significantly (p<0.05) reduced muscle tonus in patients with post-stroke spasticity of different severity. Clinical effect was seen 2 weeks after injection, it reached maximum at week 4 and then slowly decreased to week 16. The improved functional activity of the paretic arm (due to patient's and caregiver's reports) remained for to 12 weeks. The treatment was most effective in the group of patients with moderate spasticity. The correlation analysis confirmed that the severity of spasticity increased with the disease duration that reduced rehabilitation efficiency. The treatment with xeomin was safe, no serious side-effects were found. PMID- 22677664 TI - [Neuroimmune aspects of the pathogenesis and nitric oxide negative effects modifying the pathogenetic treatment of tick-borne infections]. AB - Patients with different forms of infections transmitted by Ixodidae ticks: meningeal and focal forms of tick-borne encephalitis, neuroborreliosis and mixed infection (tick-borne encephalitis + Ixodidae tick borreliosis) were examined. CD typing of lymphocytes in the cerebral spinal fluid (CSF), measuring blood and CSF cytokine content as well as blood nitric oxide (NO) metabolites were used to identify main pathogenetic mechanisms of the immune inflammation development in the central nervous system in tick-borne encephalitis associated with the hyperproduction of NO metabolites in the blood and CSF, inflammatory cytokine reaction and apoptosis. The antioxidant cytoflavin is suggested as a drug for pathogenetic treatment of neuroinfections with modifying effect of NO. The significantly rapid reduction (p<0.05) of general brain, focal brain and neuropsychological disorders as well as the decrease (p<0.05) in the endogenous hyperproduction of NO metabolites were found in patients (n=35) who received cytoflavin compared to those (n=35) who did not receive this drug. The authors recommend to use the drug in dose 10.0 ml once a day intravenously in drops during 7 - 10 days. PMID- 22677665 TI - [Diagnosis of sympathetically maintained pain in posttraumatic complex regional pain syndrome with laser Doppler flowmetry]. AB - Forty-nine patients with posttraumatic complex regional pain syndrome (CRPS) of the upper extremities were investigated by laser Doppler flowmetry (LDF) with wavelet-analysis of skin blood flow oscillations. Clinical evaluation of sympathetically maintained pain was carried out after the thoracoscopic clipping above and below the Th3 ganglion of sympathetic chain) in 33 patients and after the perivascular sympathectomy at the level of brachial artery and veins) in 16 patients. The objective diagnosis of sympathetically maintained pain was created with LDF; it was directed specially to discovery of sensory-sympathetic coupling in CRPS. Sensitivity of preoperative LDF - diagnosis was 90.2%, specificity - 87.5%, positive predictive value - 97.3%, negative predictive value - 63.6%, diagnostic effectiveness - 89.8%. PMID- 22677666 TI - [Association study of polymorphic markers of F12, PON1, PON2, NOS2, PDE4D, HIF1a, GPIba, CYP11B2 genes with ischemic stroke in Russian patients]. AB - Allele and genotype frequencies of 10 single nucleotide polymorphisms in F12, PON1, PON2, NOS2, PDE4D, HIF1a,GPIba, CYP11B2 genes were studied in a group of Russian patients with ischemic stroke (IS) from central regions of the Russian Federation and healthy donors matched for sex, age and ethnicity. The genotyping procedure included the amplification of selected DNA sequences with the following hybridization of fluorescently-labeled regions with allele-specific DNA-probes immobilized on a biochip. An analysis of allele and genotype frequencies for each gene in IS patients and controls did not reveal any significant differences. The pair-wise comparison of genes demonstrated that the frequency of the combination PON1A/-x PON2 GG was higher in the group of patients (p=0.044, OR=3.4 95% CI 1.06 - 10.4) compared to the controls and, thus, was associated with the higher risk for stroke. PMID- 22677667 TI - [Platelet cytochrome c-oxidase and glutamine synthetase-like protein in patients with mild cognitive impairment]. AB - The study aimed to develop pre-clinical diagnosis of Alzheimer's disease (AD) and - in future - preventive therapy in patients with mild cognitive impairment (MCI). The MCI group (n=44) and AD group (n=42, including 18 patients with soft dementia and 24 patients with mild dementia) were studied. The groups were matched for age (median 70 and 69 years for MCI and AD groups, respectively). The control group comprised 24 mentally healthy relatives of the patients. Correlations between the activity/amounts of platelet enzymes: cytochrome c oxidase (COX), glutamine synthetase-like protein (GSLP) and the extent of cognitive impairment were studied. The COX activity in MCI and AD groups was significantly lower than in the control group (Kruskal-Wallis test p=0.0001, chi2=11.6, p=0.003). These tests showed significant differences in GSLP amount between three groups (p=0.04 and chi2=9.38, p=0.01, respectively). Significant reverse correlation (Spearman R= -0.43, p=0.007) was found between GSLP amount and MMSE scores for MCI+AD group, i.e., the lower MMSE scores, the higher platelet GSLP level. Platelet COX and GSLP may be considered as early markers of cognitive impairment. PMID- 22677668 TI - [Dynamics of frequency of prescriptions of some psychotropic drugs for 50 years (pharmacoepidemiological study)]. PMID- 22677669 TI - [The course of acute ischemic stroke in patients with disturbances of carbohydrate metabolism]. PMID- 22677670 TI - [Atypical course of herpetic encephalitis in a adolescent]. PMID- 22677671 TI - [Polyneuromyopathy in primary hyperparathyreosis]. PMID- 22677672 TI - [Epidemiology of multiple sclerosis in the Primosky Krai and Far East regions]. AB - The first results of a clinical and epidemiological survey on prevalence, incidence, clinical characteristics, diagnosis of multiple sclerosis (MS) and medical assistance to patients in Primosky Krai, Vladivostok and the Far East regions (Sakhalin, Magadan oblasts and Kamchatka Krai) during 2005-2010 are presented. The prevalence of MS was 1.12 cases per 100000 population in the Primosky Krai in whole and from 1.61 cases in 2005 in Vladivostok to 11.45 and 16.2 cases in Primosky Krai and Vladivostok in 2010, respectively. The incidence of MS was maximal in the Primosky Krai (2.61 cases per 100 000 population in 2007 and 3.95 cases in 2008). The increase in the prevalence may be explained by the improvement of MS diagnosis, introduction of neuroimaging methods for brain structure visualization (MRI etc) and the organization of a regional MS center. The relative decrease in the MS incidence to 2.49 cases per 100 000 in 2010 was noted. Epidemiological characteristics of MS in separate oblasts of the Far East are presented. In whole, all indices indicate the moderate risk for MS in the region studied. PMID- 22677673 TI - [Association between polymorphisms of cytokine genes and the rate of multiple sclerosis progression]. AB - A genetic predisposition due to the polygenic system responsible for the formation of immune response plays a key role in the development of multiple sclerosis. We genotyped the following polymorphisms: TNFalpha (rs1800629), TNFRSF1A (rs4149584), CD40 (rs6074022 and rs11086998) using TaqMan technology. The significant genotype effect on the disability index on EDSS and rate of MS progression was found. The association between GA and AA TNFalpha genotypes and higher average annual frequency of exacerbations was revealed. Genotypes CC (rs6074022) and GG (rs11086998) were associated with the higher disability level. Genotype CC (rs11086998) was associated with the higher rate of MS progression. The results may be used as potential predictors of high rate of MS progression and allow to tailor treatment on early stages of the disease. PMID- 22677674 TI - [A retrospective study of patients with early onset of multiple sclerosis in Omskaya Oblast]. AB - To study the features of multiple sclerosis (MS) with child age-at-onset, we examined 254 patients with confirmed diagnosis of MS. The disease developed at the age younger than 16 years in 27 patients. A control group included 303 healthy volunteers. Correlations between the rate of disease progression and the age-at-onset were found. The more benign course of MS was noted in patients with earlier disease onset. There were more women and the disease frequently manifested with retrobulbar nephritis in the group with early onset. The results indicated that a G allele of -308G/A polymorphism of the TNF-alpha gene might be a risk factor for MS. The A allele may play a protective function. No association between -137G/C IL-18 polymorphism and MS was found. These polymorphisms did not contribute to the predisposition to early onset of MS. PMID- 22677675 TI - [A case of relapsing demyelinating encephalomyelitis]. PMID- 22677676 TI - [Clinical significance of T-regulatory cells in multiple sclerosis]. AB - Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system that develops due to the activation of selfreactive T-cells specific for myelin components. Regulatory T-cells CD4+CD25+Foxp3+ (T-reg) play an important role in the autoimmunity control and inhibition of T-cells-mediated myelin destruction. The aim of the study was to determine a number of T-reg in the blood of patients in different stages of disease, to evaluate their functional activity and to obtain T-reg induced ex vivo. The phenotypic analysis revealed the 2-3 fold reduction of T-reg in the exacerbation phase of MS and the increase of their content in the remission while the level of T-reg in the donor's blood remained significantly higher. The inverse correlation between the degree of severity and duration of MS and the number of T-reg was found. The suppression function of T-reg of MS patients was substantially decreased in the exacerbation and remission stages. The induction of ex vivo T-reg allows to increase the number of these cells by 30-90 times during 6-8 days. The induced T reg have phenotypic and functional characteristics of native T-reg. The adaptive cell treatment using induced T-reg may become an instrument for correction of immune dysfunction in MS. PMID- 22677678 TI - [The role of brain glucose metabolism in the development of cognitive dysfunctions in patients with remitting and secondary-progressive multiple sclerosis]. AB - To study mechanisms of development of cognitive dysfunctions in multiple sclerosis (MS), brain glucose metabolism has been investigated using PET method. We have studied 61 patients with different types of MS course. Correlations between cognitive dysfunctions and regional glucose metabolic rate were revealed. The authors suggest that metabolic dysfunctions of the grey matter play the important role in the pathogenesis of cognitive disturbances in MS. PMID- 22677677 TI - [The role of dopamine in the regulation of the interaction between nervous and immune systems in multiple sclerosis]. AB - A complex neurological and neuropsychological examination, including the detection of depression, was conducted in 71 patients with multiple sclerosis aged from 23 to 62 years (mean age 43 +/- 9 years). An immunobiochemical study included the analysis of expression of CD80 and CD86 on monocytes and B-cells, expression of TLR2 and TLR4 on monocytes, expression of D3 and D5 dopamine receptors on monocytes and B-cells, using flow cytometry, and the determination of Il-6, Il-10, IL-12p40 and dopamine plasma levels as well as vanillylmandelic acid (VMA, dopamine metabolite) urine levels measured with immunoenzyme assay. The results suggest the involvement of dopamine in the pathogenesis of depression in MS as assessed by dopamine and its metabolites levels. The role of dopamine and monocyte activation (by TLR2) in the pathogenesis of cognitive disturbances was specified as well. PMID- 22677679 TI - [Damage of macular ganglion cell complex and peripapillary retinal nerve fiber layer in multiple sclerosis]. AB - The aim of this study was to evaluate macular ganglion cell complex (GCC) characteristics and peripapillary retinal nerve fiber layer (RNFL) thickness in patients with multiple sclerosis (MS) and to investigate the associations between these parameters and clinical characteristics of patients for evaluation perspectives of using this method for monitoring of disability and neurodegenerative processes. We examined a total of 113 participants (analysis of 211 eyes), divided into three groups: 1. 48 MS patients (66 eyes) with a history of optic neuritis (ON); 2. 35 MS patients (70 eyes) without a history of ON; 3. 30 disease-free control subjects (45 eyes). The estudy included anamnesis collection, neurological examination with assessment of EDSS scores. Refracted visual acuity prior to optical coherence tomography (OCT) was tested. RTVue-100 OST system was used to assess peripapillary RNFL thickness and macular inner parameter (protocol GCC). The strongly correlated decline of the most RNFL and GCC indices was characteristic of all groups of MS patients with and without ON compared to controls. The damage of GCC was greater in patients with ON. The inverse correlation was found between the indices studied and the level of patient's disability. The study of GCC and RNFL thickness can be used to describe and characterize the level of axonal damage in MS and for objectification of neurodegenerative process in studies on neuroprotection and neuroreparation. PMID- 22677680 TI - [Symptoms of circadian desynchronization in patients with multiple sclerosis]. AB - Circadian rhythm of sleep-wakefulness and evacuation function of intestines, symptoms of neuropsychic adaptation were investigated in 36 patients, aged 21-53 years, with multiple sclerosis (MS). Frequencies of circadian rhythm disturbances of brain activity (insomnia in 66% of patients) and circadian rhythm disturbances of intestine evacuation (constipation in 72% of patients) were revealed. Insomnia and irritability in MS patients with bradyenteria occur 1.5 times more frequent than in patients with normal regulative activity of the bowels. The risk of anxiety and depression in MS patients with bradyenteria was 2-3 times higher than in patients with euenteria. The suitability of normalization of circadian desynchronization of MS patients by the restoration of optimal acrophases of circadian rhythms of the brain and bowels is established. PMID- 22677681 TI - [Lyme disease in patients with multiple sclerosis: clinical, diagnostic and therapeutic features]. AB - Lyme disease is one of the most frequent infections in the Russian Federation. In patients with multiple sclerosis, the Borrelia infection may act as a trigger in some cases and also worsens the clinical course of multiple sclerosis. One hundred patients with definite multiple sclerosis were examined including 19 patients with the combination of multiple sclerosis and Lyme disease. The difficulties of diagnosis, clinical features and treatment of Lyme disease in patients with multiple sclerosis are discussed. PMID- 22677682 TI - [The Sjogren's syndrome and multiple sclerosis: similarity and differences]. AB - Multiple sclerosis (MS) is very similar to the Sjogren's syndrome (SS) by its clinical presentations. Features found in common between the two disorders include symptoms of lesions of the brain, spinal cord and optic tract, the detection of autoantibodies, such as antinuclear, anti-Ro, anti-La and the prevalence of MRI abnormalities such as periventricular and subcortical lesions. Almost all symptoms found in patients with the CNS-SS involvement described above could be attributed to the concomitant presence of MS. Therefore, the differential diagnosis of these diseases is difficult. The paper addresses clinical and biological presentations of similarity of and differences between MS and SS in the diagnostic aspect. PMID- 22677683 TI - [Efficacy and tolerability of long-term using of glatimer acetate (copaxone): a 10 year-study in the Moscow Municipal Multiple Sclerosis center]. AB - Experience of 10-year administration of glatimer acetate (copaxone) in 74 patients with active remitting multiple sclerosis is summarized. The significant decrease in the frequency of exacerbations was seen over these ten years. Disease severity on the EDSS was stable and decreased only to the end of the 10-year period. The positive stable clinical dynamics did not depend on the disease severity at baseline. The drug was well-tolerated that allowed to control the course of multiple sclerosis: 64.8% of patients had no more than one exacerbation over 10 years and in 71.6% patients, the disease progression was absent or minimal (less than one score on EDSS). It has been concluded, that the long-term 10-year treatment with copaxone enables to control the development of disease in many patients. PMID- 22677684 TI - [Sphingosine-1-phosphate signaling system and the innovative mechanism of action of fingolimod in treatment of multiple sclerosis: review of foreign literature]. AB - Over the last years, sphingosine-1-phosphate signaling function (S1P) is thought to play a key role in the development of immunological and neurological components of multiple sclerosis (MS). Modulators of the S1P-system are highly effective in MS treatment. Fingolimod, a structural analogue of endogenous sphingosine, is a first generation drug of a new class of medications known as "modulators of sphingosine-1-phosphate receptors". The inhibition of S1P receptors by fingolimod in MS reduces the recirculation of autoreactive central memory T-cells and their infiltration of the CNS where they cause a damage that clinically reveals in the decrease in the number of MS exacerbations and less severe inflammatory brain changes in MRI. PMID- 22677685 TI - [The comparative study of efficacy and tolerability of intramuscular introduction of beta-interferon-1a in adults and adolescents with remitting multiple sclerosis]. AB - The experience of the treatment of patients with remitting multiple sclerosis (MS) with intramuscular introduction of beta-interferon-1a (avonex) is presented. Seventeen children and adolescents, aged from 11 to 18 years, and 55 adults, aged over 55 years, were treated for at least one-year period. Results revealed a significant reduction of exacerbations in both groups (from 1.35 to 0.06 in average in adolescents and from 0.86 to 0.17 in adults). The changes were accompanied by the stabilization of MS severity index: EDSS scores have decreased in 23.6% of adults and in 17.6% of adolescents. In both groups, good tolerability of the treatment was noted. There was a low probability of side-effects with the exception of increased frequency of a flu-like syndrome (47% cases) in patients younger than 18 years that demands special attention from children neurologists. The high efficacy and good tolerability and safety profile of beta-interferon-1a give grounds for administering this drug to children and adolescents with MS. PMID- 22677686 TI - Patterns and predictors of early mortality in incident hemodialysis patients: new insights. AB - BACKGROUND: Incident hemodialysis patients have the highest mortality in the first several months after starting dialysis treatments. We hypothesized that the patterns and risk factors associated with this early mortality differ from those in later dialysis therapy periods. METHODS: We examined mortality patterns and predictors during the first several months of hemodialysis treatment in 18,707 incident patients since the first week of hemodialysis therapy and estimated the population attributable fractions for selected time periods in the first 24 months. RESULTS: The 18,707 incident hemodialysis patients were 45% women and 54% diabetics. The standardized mortality ratios (95% confidence interval) in the 1st to 3rd month of hemodialysis therapy were 1.81 (1.74-1.88), 1.79 (1.72-1.86), and 1.34 (1.27-1.40), respectively. The standardized mortality ratio reached prevalent mortality only by the 7th month. No survival advantage for African Americans existed in the first 6 months. Patients with low albumin <3.5 g/dl had the highest proportion of infection-related deaths while patients with higher albumin levels had higher cardiovascular deaths including 76% of deaths during the first 3 months. Use of catheter as vascular access and hypoalbuminemia <3.5 g/dl explained 34% (17-54%) and 33% (19-45%) of all deaths in the first 90 days, respectively. CONCLUSIONS: Incident hemodialysis patients have the highest mortality during the first 6 months including 80% higher death risk in the first 2 months. The presence of a central venous catheter and hypoalbuminemia <3.5 g/dl each explain one third of all deaths in the first 90 days. PMID- 22677687 TI - Kaposi sarcoma: review and medical management update. AB - Despite recent advances in our understanding of pathogenic mechanisms involved, the true nature of Kaposi sarcoma remains an enigma. Four clinical variants have been described for the disease, differing in natural history, site of predilection, and prognosis. All forms of Kaposi sarcoma may manifest in the oral cavity and Kaposi sarcoma-associated virus appears essential to development of all clinical variants. The spectrum of therapeutic strategies is broad and selection of appropriate intervention mandates a thorough understanding of disease spread and the patient's symptomatology, as well as risks and benefits of therapy. This article provides an overview of epidemiology, subtypes, clinical course, pathogenesis, and management strategies for Kaposi sarcoma. PMID- 22677689 TI - Advantages and limits of 3-segment (paramedian) versus 2-segment (median) surgically assisted rapid maxillary expansion (SARME). AB - BACKGROUND: A novel maxillary 3-segment osteotomy (3SO) was evaluated versus the conventional 2-segment-osteotomy (2SO) for surgically assisted rapid maxillary expansion. 3SO was performed bilaterally between the lateral incisors and canines at the former junction of the lateral alveolar processes with the premaxilla. STUDY DESIGN: Of 98 included patients (n = 53 retrospectively and n = 45 prospectively; 68 complete datasets), 47 patients' preoperative and postexpansion cast models were evaluated for transverse maxillary dental and skeletal expansion, dental tipping, attachment loss, and front teeth angulation, and on photographs the pink esthetic score (PES) was assessed preoperatively versus postoperatively. RESULTS: Three-SO expanded to a larger extent with more symmetry than 2SO, at the price of more dental tipping and front teeth angulation (independent t test). The PES showed better esthetic outcomes for 3SO (Mann Whitney U test). CONCLUSIONS: Disadvantages of 2SO, such as median diastema, midline shift, median papilla infringement, asymmetric expansion, septum and columella dislocation, high forces on the periodontal apparatus, and subsequent attachment loss were overcome with 3SO. Bilateral double osteotomies appeared to promote higher volumes of callus formation, thus preventing relapses. PMID- 22677688 TI - Factors associated with length of stay and hospital charges for patients hospitalized with mouth cellulitis. AB - OBJECTIVE: Dental conditions that are neglected could progress to infectious lesions that are severe enough to require hospital admission for treatment. The objective of this study was to examine outcomes in patients hospitalized for cellulitis and abscesses of mouth in the USA in year 2008. STUDY DESIGN: The nationwide inpatient sample for the year 2008, a component database of the Healthcare Cost and Utilization Project, was used for the current study. All hospital discharges with a primary diagnosis for cellulitis or abscess of mouth (ICD-9-CM code 528.3) were selected for analysis. Outcomes, including length of stay in hospital (LOS) and hospitalization charges, were computed from the database and projected to national levels by using the discharge weight variable. The predictor variables were composed of sets of heterogeneous variables grouped into the following categories: demographic, health-related (comorbid conditions), hospital-specific, and insurance-related. The primary outcome variables were LOS and hospital charges. Multivariable linear regression analysis models were used to examine the association between predictor and outcome variables. RESULTS: A total of 4,044 hospital discharges were attributed primarily to cellulitis or abscess of mouth. About 45% of these discharges occurred in those aged between 18 and 45 years. The mean length of stay in hospital was 3.9 days, and the mean hospital charge was $24,290. The total USA hospitalization charge was close to $98 million. Private insurance plans were the major payers, accounting for $31 million of hospitalization charges. About 88% of all hospitalization were discharged routinely after treatment, and 2% were transfered to another short term hospital. CONCLUSIONS: This study examines outcomes in patients hospitalized for cellulitis or abscess of mouth. Future studies must focus on identifying cohorts that are more prone to developing odontogenic infections that are severe enough to warrant hospitalization. PMID- 22677690 TI - Hemimandibulectomy after bisphosphonate treatment for complex regional pain syndrome: a case report and review on the prevention and treatment of bisphosphonate-related osteonecrosis of the jaw. AB - BACKGROUND: The increase in reported cases of osteonecrosis of the jaw has increased the clinical significance of bisphosphonate therapeutic agents in the dentistry field. METHODS: We present a rare and severe case of bisphosphonate related osteonecrosis of the jaw caused by medicamentous treatment of complex regional pain syndrome. This article reviews the current international prevention and treatment guidelines with regard to bisphosphonate treatment. RESULTS: Even rare indications for bisphosphonate treatment may lead to devastating effects on the patient. CONCLUSIONS: Dentists and physicians who prescribe bisphosphonates should be familiar with the side effects of these drugs and the management of these side effects. To prevent negative outcomes, it is important that there be a close collaboration among the doctors involved and that a thorough medical history is obtained; this is especially true because the range of indications for bisphosphonate treatment increases every year. PMID- 22677691 TI - Local injection of nerve growth factor via a hydrogel enhances bone formation during mandibular distraction osteogenesis. AB - OBJECTIVE: The objective of this study was to evaluate the effects of the injectable NGF-carrying collagen/nano-hydroxyapatite/alginate hydrogel on the bone formation in a rabbit mandibular distraction osteogenesis model. STUDY DESIGN: Thirty-five New Zealand white rabbits underwent bilateral madibular distraction osteogenesis at a rate of 0.75 mm/12 h for 6 days. The rabbits were divided into 4 groups: group 1 received injections of collagen/nano hydroxyapatite/alginate hydrogel containing hNGFbeta; groups 2, 3, and 4 received injections of hNGFbeta, Col/nHA/Alg hydrogel, and saline, respectively. The injections were performed on both sides of the mandible at the end of the lengthening phase. All the animals were killed at a consolidation time of 14 days. RESULTS: No difference in regenerate bone dimensions was observed among the 4 groups. Bone mineral density, the maximum load, and the bone volume/total volume of the new bone in the distraction gap in group 1 was significantly greater (P < .05) than in the other 3 groups. CONCLUSIONS: Application of the Col/nHA/Alg hydrogel as an NGF delivery during the consolidation phase of distraction osteogenesis increased regeneration and new bone formation. PMID- 22677692 TI - Two-piece customized mold technique for high-dose-rate brachytherapy on cancers of the buccal mucosa and lip. AB - OBJECTIVE: High-dose-rate (HDR) brachytherapy using a customized mold is a minimally invasive treatment for oral cancer; however, it is difficult to use this technique for buccal and lip cancers involving the commissura labiorum, owing to its anatomic form. The purpose of this study was to introduce an improved customized mold consisting of 2 pieces to allow the fixation of molds to these sites. STUDY DESIGN: Five patients with buccal carcinoma and 1 patient with lip carcinoma were treated with this technique after external beam radiotherapy. One patient with neck metastasis underwent both neck dissection and partial tumor resection before HDR brachytherapy. RESULTS: At the end of the follow-up period, 5 patients had no tumor recurrence, and 1 patient had suffered local recurrence. CONCLUSIONS: Our technique is a viable therapeutic option for patients with buccal and lip carcinomas for whom the therapeutic modalities are limited by age, performance status, and other factors. PMID- 22677693 TI - New scoring charts for GPs are too crude, say doctors' leaders. PMID- 22677694 TI - Anticoagulants cause the most serious adverse events, finds US analysis. PMID- 22677695 TI - GP practice shed vulnerable elderly patients to save money, NHS probe finds. PMID- 22677696 TI - Intraoperative imaging and off-pump ligation of coronary artery fistula. PMID- 22677697 TI - Bioengineering of carbon fixation, biofuels, and biochemicals in cyanobacteria and plants. AB - Development of sustainable energy is a pivotal step towards solutions for today's global challenges, including mitigating the progression of climate change and reducing dependence on fossil fuels. Biofuels derived from agricultural crops have already been commercialized. However the impacts on environmental sustainability and food supply have raised ethical questions about the current practices. Cyanobacteria have attracted interest as an alternative means for sustainable energy productions. Being aquatic photoautotrophs they can be cultivated in non-arable lands and do not compete for land for food production. Their rich genetic resources offer means to engineer metabolic pathways for synthesis of valuable bio-based products. Currently the major obstacle in industrial-scale exploitation of cyanobacteria as the economically sustainable production hosts is low yields. Much effort has been made to improve the carbon fixation and manipulating the carbon allocation in cyanobacteria and their evolutionary photosynthetic relatives, algae and plants. This review aims at providing an overview of the recent progress in the bioengineering of carbon fixation and allocation in cyanobacteria; wherever relevant, the progress made in plants and algae is also discussed as an inspiration for future application in cyanobacteria. PMID- 22677698 TI - Neurodevelopmental outcome of infants resuscitated with air or 100% oxygen: a systematic review and meta-analysis. AB - BACKGROUND: The use of air for the initial resuscitation of newborn infants has been shown to reduce neonatal mortality. However, a precise estimate of the neurodevelopmental status upon follow-up of infants resuscitated in air is lacking. OBJECTIVE: To perform a meta-analysis of all studies reporting resuscitation of newborn infants with air or 100% oxygen that included follow-up data. METHODS: Bibliographic databases were searched. In addition, we estimated the effect of loss to follow-up on our analysis of abnormal neurodevelopmental outcome. RESULTS: We identified 10 studies in which newborn infants had been randomly or quasi-randomly assigned to resuscitation with air or 100% oxygen. Three of these 10 studies had available follow-up data. A total of 678 infants were enrolled at centers that performed follow-up of these infants. Of these, 113 died, leaving 565 infants potentially eligible for follow-up. A total of 414 children were evaluated (73% of eligible children; 195 resuscitated with air and 219 with 100% oxygen). In the air group, 12.8% of infants had an abnormal neurodevelopmental outcome, compared with 10.5% in the 100% oxygen group [typical relative risk (RR) 1.24, 95% confidence interval 0.73-2.10]. This is consistent with an RR of abnormal development as low as 0.41 or as high as 2.28. CONCLUSIONS: Long-term follow-up did not detect any significant differences in these two groups regarding abnormal development. However, the results are imprecise and could be consistent with significant harm or benefit. PMID- 22677699 TI - Intravesical recurrence after surgical management of urothelial carcinoma of the upper urinary tract. AB - OBJECTIVES: To elucidate clinicopathological risk factors for intravesical recurrence (IVR) in patients undergoing nephroureterectomy for upper urinary tract urothelial carcinoma (UUT-UC). METHODS: We identified a study population of 151 consecutive patients without previous or concurrent bladder cancer who underwent nephroureterectomy for UUT-UC. IVR was assessed in relation to tumor location, size, and multifocality, operation modality and time, stage, grade, lymphovascular invasion, regional lymph node metastasis, preoperative urinary cytology, and perioperative chemotherapy. The median follow-up time was 24 months. RESULTS: Of 151 patients, 51 (34%) developed IVR after nephroureterectomy, and 50 (98%) of the patients presented with IVR within 2 years. Tumor multifocality and site (located in ureter) were determined as risk factors for IVR by univariate analysis. In a multivariate analysis, only tumor multifocality (relative risk: 4.024, p = 0.001) was an independent predictor of IVR. Ten-year cancer-specific survival rates for the patients with and without IVR were 68 and 52%, respectively (p = 0.06). CONCLUSIONS: Tumor multifocality is a significant risk factor in developing IVR after surgery for UUT-UC. These results indicate that despite most IVR occurring within 2 years of treatment, it is necessary to follow such patients more closely using cystoscopy. However, IVR is unlikely to indicate a poorer prognosis. PMID- 22677700 TI - Trauma and thrombelastography: how changes in the understanding of coagulopathy, testing, and hospital systems have changed one group's practice. AB - Bleeding disorders associated with trauma are of paramount importance when dealing with the acutely injured individual. Statistically, up to 40% of trauma related deaths are assumed to be related to hemorrhage. Historically, there have been many varying positions on the way to handle this entity. Ironically, it is not always the injury but the physiologic sequelae of that injury that lead to trauma associated deaths. Over time, newer theories have been developed to help the clinician begin to understand the etiology and treatment of this process. The purpose of this paper is to review current literature and explain how these new concepts helped change practice in an urban, academic, Level One Trauma Center. PMID- 22677701 TI - Effect of PET/CT on management of patients with non-small cell lung cancer: results of a prospective study with 5-year survival data. AB - We investigated the incremental management impact and prognostic value of staging with (18)F-FDG PET/CT in patients with non-small cell lung cancer (NSCLC) being considered for potentially curative therapies. METHODS: Information on 168 consecutive patients with NSCLC being considered for surgery or definitive radiotherapy with curative intent before PET/CT was entered into a prospective database. The pre-PET/CT management plan, based on conventional imaging (conventional CT, appropriately supplemented by bone scintigraphy or other modalities), was defined prospectively by referring clinicians before PET/CT results became available. After PET/CT, actual clinical management was recorded, and patients were followed up until 5 y or death. The appropriateness of PET/CT management plans was assessed by biopsy when available, clinical follow-up, and survival analysis. RESULTS: Stage was discordant on PET/CT and conventional imaging in 50.6% of patients (41.1% upstaged, 9.5% downstaged), with high management impact (change in treatment modality or curative intent) in 42.3% of patients. Both conventional imaging stage and PET/CT stage were strongly predictive of overall survival (OS) but there were greater differences between hazard rates and separations in the OS curves for stage groupings determined using PET/CT. OS was also strongly predicted by PET/CT-directed choice of therapy (P < 0.0001). CONCLUSION: PET/CT frequently affects patient management and strongly predicts OS in NSCLC, supporting the appropriateness of such changes. PMID- 22677702 TI - Randomized controlled trials on PET: a systematic review of topics, design, and quality. AB - Randomized controlled trials (RCTs) add important information to diagnostic accuracy studies in the evaluation of PET and PET/CT. We evaluated how many RCTs on PET existed, which clinical topics they addressed, and what their design and quality were. METHODS: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (Clinical Trials) up to August 2010. We also searched in ClinicalTrials.gov and the International Clinical Trials Registry Platform for ongoing RCTs up to March 2011. Titles and abstracts and full texts were screened independently by 2 reviewers. Study characteristics were extracted with standard extraction sheets for ongoing and published RCTs, and risk of bias was assessed for published ones. RESULTS: We identified 54 RCTs, 12 of which were published. The main topics in published studies were non-small cell lung cancer and colorectal cancer; only 3 were conducted in nononcologic fields (this trend was similar in ongoing studies, in which the most common topic was Hodgkin disease). The main indications in the oncologic PET studies were staging in published studies and restaging (mostly including an early assessment of treatment response) in ongoing ones. All except 1 of the published studies applied a marker-based strategy design, whereas about 43% (18/42) of ongoing studies use a more efficient design (Enrichment Design or Marker by Treatment Interaction Design). CONCLUSION: A relatively high number of ongoing RCTs of PET in several oncologic fields are expected to produce robust results over the next few years. For nononcologic topics, further high-quality studies are still needed to ascertain the benefit of this technique for patients. As funding is usually difficult in nondrug topics, alternative concepts of funding, which should also involve the manufacturers of diagnostic devices, but also more efficient study designs, should be applied to bridge the evidence gap on PET in the near future. PMID- 22677703 TI - Advances in the clinical applications of exhaled nitric oxide measurements. AB - This article focuses on recent data which highlight the clinical settings in which exhaled nitric oxide (F(E)NO) is potentially helpful, or not, as a clinical tool. It is becoming clearer that, selectively applied, F(E)NO measurements can provide reliable clinical guidance, particularly when values are low. Such values are associated with high negative predictive values (>90%). Increased F(E)NO levels are associated with much more modest positive predictive values (75%-85%) and these are less reliable. These general principles apply when diagnosing steroid responsiveness in relation to asthma, chronic cough, and COPD. Although randomised trials do not support routine use of exhaled NO measurements in uncomplicated bronchial asthma, there is evidence that in patients with difficult asthma, or asthma associated with pregnancy, F(E)NO enhances overall management, and the decision to commence or increase inhaled steroid therapy (yes/no) may be made more accurately. Exhaled NO is potentially relevant in the assessment of occupational asthma (serial measurements) and also in diagnosing bronchiolitis obliterans in lung transplant patients. PMID- 22677704 TI - Xanthogranulomatous cholecystitis: catching the culprit--clinical and imaging analysis. AB - BACKGROUND: Radiological and intraoperative findings of xanthogranulomatous cholecystitis (XGC) mimic carcinoma gallbladder (CaGB) leading to extended surgical resections and increased morbidity. We reviewed the clinical and CECT findings of histopathologically proven XGC and compared them with those of CaGB. METHODS: The clinical and CECT findings from 22 patients with XGC were compared with 15 patients with CaGB manifesting as diffuse wall thickening. RESULTS: GB wall thickness was similar in both groups (XGC 12.4 +/- 3 mm, CaGB 13.9 +/- 6.5 mm; p = 0.61). Intramural hypoattenuating nodules occupying >60% of the GB wall were suggestive of XGC, while the absence of nodules suggested CaGB (p = 0.017). The mucosal lining was intact and enhancing in XGC (20/22) and disrupted in CaGB (10/15; p = 0.001). Among adjacent organ infiltration, bile duct invasion resulting in obstruction was a significant finding in patients with CaGB (p = 0.04). Among XGC patients, 11 patients underwent radical cholecystectomy, 10 had open cholecystectomy and frozen section and 1 underwent bypass. CONCLUSIONS: Though there is an overlap between XGC and CaGB, the presence of intramural hypoattenuating nodules occupying >60% of the diffusely thickened GB wall with intact mucosal line and the absence of obstructive features suggest XGC. In the presence of such imaging features, frozen biopsy should be done before proceeding with mutilating radical surgery. PMID- 22677705 TI - Setting the stage for cohesion establishment by the replication fork. PMID- 22677706 TI - Proton-gated ion channels in mouse bone marrow stromal cells. AB - A variety of ion channels like acid sensing ion channels (ASICs) and several members of the transient receptor potential (TRP) cation channel family are known to be activated by protons. The present study describes proton-gated current in mouse bone marrow stromal cells (BMSCs), by using whole cell patch clamp. Rapid application of extracellular solution of pH <= 6.5, evoked slow inactivating current with mean peak value of 328 +/- 31pA, (n = 25) at pH 5.0. The reversal potential was close to the theoretical Na(+) equilibrium potential, indicating that majority of the current is mediated by Na(+) and partially carried by Ca(2+) as revealed by ion substitution experiments and Ca(2+) imaging. ASICs blocker amiloride (1mM) and nonselective cation channel blocker flufenamic acid (0.3mM) reduced the current amplitudes by 36 +/- 5% (n = 10) and 39 +/- 7% (n = 14) respectively. Co-application of flufenamic acid and amiloride further decreased the current by 70 +/- 7% (n = 7). However, capsazepine, SKF 96365 and ruthenium red had no effect. 10mM of Ca(2+) and 2mM of La(3+) inhibited the current by 39 +/- 6% (n = 5) and 46 +/- 6% (n = 4) respectively. Zn(2+) (300 MUM) and Gd(3+) (500 MUM) had no effect on the current amplitude. Low pH mediated cell death was completely inhibited by co-application of La(3+) and amiloride. Reverse Transcriptase-PCR detected expression of mRNAs of ASICs and TRP family. In summary, our results demonstrate the functional expression of low pH-activated ion channels in mouse BMSCs. PMID- 22677707 TI - Organotypic modeling of human keratinocyte response to peroxisome proliferators. AB - Peroxisome proliferators (PPs) are a diverse chemical group including hypolipidemic drugs and some fatty acids. Their stimulation of PP-activated receptors (PPARs) and subsequent control of gene expression regulates metabolism and differentiation in many cells. PPs have multiple opportunities to target human epidermal keratinocytes because of delivery through dietary, clinical, and/or topical exposure routes. PPAR knockout mice and PP treatment of mouse skin or human keratinocytes in monolayer culture have established some effects for PPs in cutaneous differentiation. However, incomplete epidermal maturation characteristic of monolayer keratinocytes and rodent-specific effects may limit our full understanding of human keratinocyte responses to PPs. To address these issues, we investigated PP influence on primary human keratinocytes in organotypic cultures that recapitulate biochemical markers of epidermis. We found that the PPARalpha agonists clofibrate, docasohexaenoic acid, and WY-14,643 produced mild to moderate keratinocyte hyperplasia, increased stratification (particularly of granular and cornified layers), and enhanced levels of the differentiation markers filaggrin, ABCA12, and phosphorylated HSP27. Several PP effects generated in the organotypic system, however, were distinct from those previously reported for rodent skin and human keratinocyte monolayer cultures, suggesting that the species and growth context of target cells can impact exposure outcomes. Given the utility of organotypic cultures for modeling the epidermis, studies in this system may bridge the gap between the rodent assays and clinical studies of human epidermal responses to PPs. PMID- 22677708 TI - Theory, modelling and simulation in origins of life studies. AB - Origins of life studies represent an exciting and highly multidisciplinary research field. In this review we focus on the contributions made by theory, modelling and simulation to addressing fundamental issues in the domain and the advances these approaches have helped to make in the field. Theoretical approaches will continue to make a major impact at the "systems chemistry" level based on the analysis of the remarkable properties of nonlinear catalytic chemical reaction networks, which arise due to the auto-catalytic and cross catalytic nature of so many of the putative processes associated with self replication and self-reproduction. In this way, we describe inter alia nonlinear kinetic models of RNA replication within a primordial Darwinian soup, the origins of homochirality and homochiral polymerization. We then discuss state-of-the-art computationally-based molecular modelling techniques that are currently being deployed to investigate various scenarios relevant to the origins of life. PMID- 22677709 TI - Editorial commentary: asymptomatic bacteriuria--shift of paradigm. PMID- 22677710 TI - The role of asymptomatic bacteriuria in young women with recurrent urinary tract infections: to treat or not to treat? AB - BACKGROUND: Little is known about the role of asymptomatic bacteriuria (AB) treatment in young women affected by recurrent urinary tract infection (UTI). We aimed to evaluate the impact of AB treatment on the recurrence rate among young women affected by recurrent UTI. METHODS: A total of 673 consecutive asymptomatic young women with demonstrated bacteriuria from January 2005 to December 2009 were prospectively enrolled. Patients were split into 2 groups: not treated (group A, n = 312) and treated (group B, n = 361). Microbiological and clinical evaluations were performed at 3, 6, and 12 months. Quality of life was also measured. Recurrence-free rate at the end of the entire study period was the main outcome measure. RESULTS: At baseline, the 2 most commonly isolated pathogens were Escherichia coli (group A, 38.4%; group B, 39.3%) and Enterococcus faecalis (group A, 32.7%; group B, 33.2%). At the first follow-up visit, there was no difference between the 2 groups (relative risk [RR], 1.05; 95% confidence interval [CI], 1.01-1.10), whereas after 6 months, 23 (7.6%) in group A and 98 (29.7%) in group B showed recurrence with a statistically significant difference (RR, 1.31; 95% CI, 1.21-1.42; P < .0001). At the last follow-up, 41 (13.1%) in group A and 169 (46.8%) in group B showed recurrence (RR, 3.17; 95% CI, 2.55 3.90; P < .0001). One patient in group A and 2 patients in group B were found to have pyelonephritis. CONCLUSIONS: This study shows that AB should not be treated in young women affected by UTI, suggesting it may play a protective role in preventing symptomatic recurrence. PMID- 22677711 TI - Is the gram stain useful in the microbiologic diagnosis of VAP? A meta-analysis. AB - In a meta-analysis examining respiratory specimen Gram stain for diagnosis of ventilator-associated pneumonia, absence of bacteria on Gram stain had a high negative predictive value, but a positive Gram stain correlated poorly with organisms recovered in culture. Rapid and accurate diagnosis of ventilator associated pneumonia (VAP) is a major challenge and no generally accepted gold standard exists for VAP diagnosis. We conducted a meta-analysis to examine the role of respiratory specimen Gram stain to diagnose VAP, and the correlation with final culture results. In 21 studies, pooled sensitivity of Gram stain for VAP was 0.79 (95% confidence interval [CI], .77-0.81; P < .0001) and specificity was 0.75 (95% CI, .73-.78; P < .0001). Negative predictive value of Gram stain for a VAP prevalence of 20%-30% was 91%, suggesting that VAP is unlikely with a negative Gram stain but the positive predictive value of Gram stain was only 40%. Pooled kappa was 0.42 for gram-positive organisms and 0.34 for gram-negative organisms, suggesting fair concordance between organisms on Gram stain and recovery by culture. Therefore, a positive Gram stain should not be used to narrow anti-infective therapy until culture results become available. PMID- 22677713 TI - Early-onset liver fibrosis due to primary hepatitis C virus infection is higher over time in HIV-infected men. PMID- 22677714 TI - Ivermectin binding sites in human and invertebrate Cys-loop receptors. AB - Ivermectin is a gold standard antiparasitic drug that has been used successfully to treat billions of humans, livestock and pets. Until recently, the binding site on its Cys-loop receptor target had been a mystery. Recent protein crystal structures, site-directed mutagenesis data and molecular modelling now explain how ivermectin binds to these receptors and reveal why it is selective for invertebrate members of the Cys-loop receptor family. Combining this with emerging genomic information, we are now in a position to predict species sensitivity to ivermectin and better understand the molecular basis of ivermectin resistance. An understanding of the molecular structure of the ivermectin binding site, which is formed at the interface of two adjacent subunits in the transmembrane domain of the receptor, should also aid the development of new lead compounds both as anthelmintics and as therapies for a wide variety of human neurological disorders. PMID- 22677716 TI - Inter-examiner reliability of active combined movements assessment of subjects with a history of mechanical neck problems. AB - Combined movement examination (CME) is used in clinical management of spinal dysfunction. Whilst reliability of lumbar spine CME has been investigated, reliability of cervical spine CME is unclear. The aim of this study was to assess the inter-rater reliability of a CME protocol in subjects who have previously experienced a neck problem. Subjects were evaluated to identify their "side of discomfort", "dysfunctional active prime movement (PrM)", "prime combination of movements (PrC)" and "stretch pattern". A secondary aim included the evaluation of a movement order effect. Inter-rater reliability of CME was evaluated in subjects (n = 25) with a history of mechanical neck problems. Through questioning and visual observation of the "functional demonstration", raters (n = 3) had to classify subjects in anterior or posterior stretch patterns and determine movement combinations. Descriptive data for "PrC" showed moderate (67%) percentage agreement for anterior pattern and excellent (92%) for posterior pattern. AC1 values (95% Confidence Interval) were calculated for "Side" (AC1 = 0.96, CI: 0.89-1) and "Pattern" (AC1 = 0.96, CI: 0.89-1) demonstrating excellent inter-examiner reliability. "PrM" demonstrated total (100%) agreement. Establishing an order effect was unreliable (anterior pattern: 33%; posterior pattern: 38%). Results showed that a CME based protocol is a reliable assessment tool. Further research using larger samples and other clinical presentations is warranted. PMID- 22677717 TI - Vitamin E as a functional and biocompatibility modifier of synthetic hemodialyzer membranes: an overview of the literature on vitamin E-modified hemodialyzer membranes. AB - Along with one century of history, research has provided many solutions for hemodialysis (HD) biomaterials, encompassing several generations of copolymers that have found wide application in the development of hollow-fiber dialyzer membranes. Polysulfone-based biomaterials have gained increasing consideration and are now the gold standard in the production of biocompatible hemodialyzers. However, even the highest biocompatibility now available cannot exclude that dialyzer membranes and the overall extracorporeal circulation may produce at the subclinical level immunoinflammatory reactions and thus an increased cardiovascular risk of patients on regular HD therapy. The lipophilic antioxidant and radical scavenger vitamin E has been used (as alpha-tocopherol) to modify cellulosic and synthetic hollow-fiber membranes with the ultimate goal to neutralize harmful reactive species and to mimic lipid structures of blood cell plasmalemma and lipoprotein particles. Besides filtration and biocompatibility, this modifier has introduced a third function of dialyzer membranes, namely 'antioxidant bioactivity'. Vitamin E can also serve as a template molecule to produce synthetic redox-active and -silent (non-antioxidant) modifiers for future generations of dialyzer membranes. This mini-review article describes the evolution of vitamin E-derived copolymers as a generation of biomaterials that has offered a clinical challenge and still represents a chance to further improving the quality of HD therapy. PMID- 22677715 TI - Structural and immunologic characterization of bovine, horse, and rabbit serum albumins. AB - Serum albumin (SA) is the most abundant plasma protein in mammals. SA is a multifunctional protein with extraordinary ligand binding capacity, making it a transporter molecule for a diverse range of metabolites, drugs, nutrients, metals and other molecules. Due to its ligand binding properties, albumins have wide clinical, pharmaceutical, and biochemical applications. Albumins are also allergenic, and exhibit a high degree of cross-reactivity due to significant sequence and structure similarity of SAs from different organisms. Here we present crystal structures of albumins from cattle (BSA), horse (ESA) and rabbit (RSA) sera. The structural data are correlated with the results of immunological studies of SAs. We also analyze the conservation or divergence of structures and sequences of SAs in the context of their potential allergenicity and cross reactivity. In addition, we identified a previously uncharacterized ligand binding site in the structure of RSA, and calcium binding sites in the structure of BSA, which is the first serum albumin structure to contain metal ions. PMID- 22677719 TI - A pain in the neck. Latent mycobacterium tuberculosis. PMID- 22677720 TI - Claudin-4-targeted optical imaging detects pancreatic cancer and its precursor lesions. AB - OBJECTIVES: Novel imaging methods based on specific molecular targets to detect both established neoplasms and their precursor lesions are highly desirable in cancer medicine. Previously, we identified claudin-4, an integral constituent of tight junctions, as highly expressed in various gastrointestinal tumours including pancreatic cancer. Here, we investigate the potential of targeting claudin-4 with a naturally occurring ligand to visualise pancreatic cancer and its precursor lesions in vitro and in vivo by near-infrared imaging approaches. DESIGN: A non-toxic C-terminal fragment of the claudin-4 ligand Clostridium perfringens enterotoxin (C-CPE) was labelled with a cyanine dye (Cy5.5). Binding of the optical tracer was analysed on claudin-4 positive and negative cells in vitro, and tumour xenografts in vivo. In addition, two genetically engineered mouse models for pancreatic intraepithelial neoplasia (PanIN) and pancreatic cancer were used for in vivo validation. Optical imaging studies were conducted using 2D planar fluorescence reflectance imaging (FRI) technology and 3D fluorescence-mediated tomography (FMT). RESULTS: In vitro, the peptide-dye conjugate showed high binding affinity to claudin-4 positive CAPAN1 cells, while claudin-4 negative HT1080 cells revealed little or no fluorescence. In vivo, claudin-4 positive tumour xenografts, endogenous pancreatic tumours, hepatic metastases, as well as preinvasive PanIN lesions, were visualised by FRI and FMT up to 48 h after injection showing a significantly higher average of fluorochrome concentration as compared with claudin-4 negative xenografts and normal pancreatic tissue. CONCLUSIONS: C-CPE-Cy5.5 combined with novel optical imaging methods enables non-invasive visualisation of claudin-4 positive murine pancreatic tumours and their precursor lesions, representing a promising modality for early diagnostic imaging. PMID- 22677718 TI - A randomised controlled study of the effect of cholinesterase inhibition on colon function in patients with diabetes mellitus and constipation. AB - OBJECTIVES: Chronic constipation in diabetes mellitus is associated with colonic motor dysfunction and is managed with laxatives. Cholinesterase inhibitors increase colonic motility. This study evaluated the effects of a cholinesterase inhibitor on gastrointestinal and colonic transit and bowel function in diabetic patients with constipation. DESIGN: After a 9-day baseline period, 30 patients (mean +/- SEM age 50 +/- 2 years) with diabetes mellitus (18 type 1, 12 type 2) and chronic constipation without defaecatory disorder were randomised to oral placebo or pyridostigmine, starting with 60 mg three times a day, increasing by 60 mg every third day up to the maximum tolerated dose or 120 mg three times a day; this dose was maintained for 7 days. Gastrointestinal and colonic transit (assessed by scintigraphy) and bowel function were evaluated at baseline and the final 3 and 7 days of treatment, respectively. Treatment effects were compared using analysis of covariance, with gender, body mass index and baseline colonic transit as covariates. RESULTS: 19 patients (63%) had moderate or severe autonomic dysfunction; 16 (53%) had diabetic retinopathy. 14 of 16 patients randomised to pyridostigmine tolerated 360 mg daily; two patients took 180 mg daily. Compared with placebo (mean +/- SEM 1.98 +/- 0.17 (baseline), 1.84 +/- 0.16 (treatment)), pyridostigmine accelerated (1.96 +/- 0.18 (baseline), 2.45 +/- 0.2 units (treatment), p<0.01) overall colonic transit at 24 h, but not gastric emptying or small-intestinal transit. Treatment effects on stool frequency, consistency and ease of passage were significant (p <= 0.04). Cholinergic side effects were somewhat more common with pyridostigmine (p=0.14) than with placebo. CONCLUSIONS: Cholinesterase inhibition with oral pyridostigmine accelerates colonic transit and improves bowel function in diabetic patients with chronic constipation. PMID- 22677723 TI - Evaluation of anatomy of impacted third molars: is 3-dimensional imaging always a necessity? PMID- 22677722 TI - ObesiTV: how television is influencing the obesity epidemic. AB - Obesity is a major public health concern in the United States. Over the last several decades, the prevalence of obesity among both adults and children has grown at an alarming rate and is now reaching epidemic proportions. The increase in obesity has been associated with rises in a host of other chronic conditions including cardiovascular disease, type 2 diabetes, and some cancers. While the causes of obesity are multifaceted, there is growing evidence that television viewing is a major contributor. Results of numerous studies indicate a direct association between time spent watching television and body weight. Possible explanations for this relationship include: 1) watching television acts as a sedentary replacement for physical activity; 2) food advertisements for nutrient poor, high-calorie foods stimulate food intake; and 3) television viewing is associated with "mindless" eating. In addition to decreasing physical activity and increasing the consumption of highly palatable foods, television viewing can also promote weight gain in indirect ways, such as through the use of targeted product placements in television shows; by influencing social perceptions of body image; and airing programs that portray cooking, eating and losing weight as entertainment. This paper will provide an interdisciplinary review of the direct and indirect ways in which television influences the obesity epidemic, and conclude with ways in which the negative impact of television on obesity could be reduced. PMID- 22677721 TI - Versatility of the mouse reversal/set-shifting test: effects of topiramate and sex. AB - The ability to learn a rule to guide behavior is crucial for cognition and executive function. However, in a constantly changing environment, flexibility in terms of learning and changing rules is paramount. Research suggests there may be common underlying causes for the similar rule learning impairments observed in many psychiatric disorders. One of these common anatomical manifestations involves deficits to the GABAergic system, particularly in the frontal cerebral cortical regions. Many common anti-epileptic drugs and mood stabilizers activate the GABA system with the reported adverse side effects of cognitive dysfunction. The mouse reversal/set-shifting test was used to evaluate effects in mice given topiramate, which is reported to impair attention in humans. Here we report that in mice topiramate prevents formation of the attentional set, but does not alter reversal learning. Differences in the GABA system are also found in many neuropsychiatric disorders that are more common in males, including schizophrenia and autism. Initial findings with the reversal/set-shifting task excluded female subjects. In this study, female mice tested on the standard reversal/set-shifting task showed similar reversal learning, but were not able to form the attentional set. The behavioral paradigm was modified and when presented with sufficient discrimination tasks, female mice performed the same as male mice, requiring the same number of trials to reach criterion and form the attentional set. The notable difference was that female mice had an extended latency to complete the trials for all discriminations. In summary, the reversal/set-shifting test can be used to screen for cognitive effects of potential therapeutic compounds in both male and female mice. PMID- 22677724 TI - Bleed or die? A bloody simple decision. PMID- 22677725 TI - Evidence does not support the discontinuation of warfarin before a dental extraction. PMID- 22677726 TI - Should warfarin be discontinued before a dental extraction? PMID- 22677729 TI - True or false facial artery aneurysm. PMID- 22677730 TI - Oncolytic viruses: a new paradigm for treatment of head and neck cancer. PMID- 22677731 TI - Retrospective analysis of 314 orbital fractures. AB - OBJECTIVE: The aim of this study was to retrospectively review the orbital fractures treated at our institution, especially epidemiologic aspects, treatment options, and postoperative sequelae. STUDY DESIGN: Three hundred fourteen patients with orbital fractures treated at the Department of Oral and Maxillofacial Surgery of the Central University Hospital in Asturias (Spain) between 2000 and 2006 were retrospectively reviewed. The patients were evaluated by age, gender, etiology, diagnostic tools, fracture pattern, treatment, and complications. RESULTS: The most common causes of injury were motor vehicle accidents (29.6%), followed by falls (27.4%). Men in the sixth decade were most affected. One hundred forty-four patients (46%) underwent internal fixation with titanium miniplates, and 17 (5.4%) required orbit floor implants. The most frequent sequelae were infraorbital nerve hypoesthesia (24.5%), enophthalmos (3.8%), and diplopia (2.2%). CONCLUSIONS: In our area of 1 million inhabitants, falls are the second cause of orbital fractures, which can be attributed to the large aged population. Postoperative complications cannot be definitely evaluated until a few months after the surgery. PMID- 22677732 TI - Sympathetic ophthalmia: a review of literature. AB - Sympathetic ophthalmia (SO), also known assympathetic uveitis, is a rare bilateral granulomatous panuveitis that occurs after a penetrating injury to an eye. After injury from either surgery or accident, a variable period of time passes before a sight-threatening inflammation develops in both the eyes. The disease usually responds rapidly to corticosteroid therapy, but recalcitrant cases may require the addition of other immunosuppressive agents. A severely injured eye with no prognosis for vision should be enucleated within 2 weeks of injury to prevent SO. The purpose of this article is to highlight the risks of SO associated with the orbital fractures involving soft tissue components of the orbit. Though unusual, a maxillofacial surgeon, while operating on the orbital walls involving the soft tissue disruption, has to be aware of this condition so that the postoperative complications related to vision can be avoided. PMID- 22677733 TI - A new coronal scalp technique to treat craniofacial fracture: the supratemporalis approach. AB - OBJECTIVE: A new coronal scalp approach, denoted as the supratemporalis approach, was designed to address facial nerve injury induced by the traditional coronal scalp approach. STUDY DESIGN: First, the complication rate among 38 cases operated upon with the traditional coronal scalp approach was analyzed retrospectively. Then 40 cases were operated upon using the supratemporalis approach. The rate of complications was recorded. The follow-up periods were 3-17 months. RESULTS: The facial contours and functions recovered well after the operation in all 78 cases. Seven cases of facial nerve injury, 1 of which was permanent, were observed in the group treated with the traditional coronal scalp approach. No case of facial nerve injury was observed in the group treated with the supratemporalis approach. CONCLUSIONS: The supratemporalis approach prevented facial nerve injury and did not increase the frequency of other complications. It is therefore worthy of application in the clinical setting. PMID- 22677734 TI - Distraction osteogenesis in the dog mandible under 60-Gy irradiation. AB - OBJECTIVE: The objective of this study was to explore the probability of distraction osteogenesis (DO) in the irradiated dog mandible after 60-Gy irradiation. STUDY DESIGN: Fourteen Chinese dogs were randomly divided into 2 groups. Twelve dogs received a preoperative unilateral irradiation from (60)Co (group R) in the mandible with a total dose of 24.8 Gy in four 6.2-Gy fractions (biologically equivalent to 60 Gy/25 fractions). The other 2 dogs without irradiation served as the control (group C). Bilateral corticotomies were made 6 months after completion of irradiation. Bone distraction was activated at a rate of 0.5 mm twice daily for 10 days after a 1-week latency period, followed by a consolidation phase of 8 weeks. The inferior alveolar nerve (IAN) underwent electrophysiologic analysis. Dog mandibles were subsequently subjected to histologic and radiographic analysis. RESULTS: All the animals had successful distractions. After 8 weeks of consolidation, no difference was found between the percentage area of new bone in both groups. New bone was more mature and organized in group C than in group R. The action potential of IAN showed corresponding alternation during the irradiation and distraction process. CONCLUSIONS: Based on this study it seems that DO may be feasible in dog mandible under 60-Gy irradiation. Further research is indicated. PMID- 22677735 TI - Improved sedation for dental extraction by using video eyewear in conjunction with nitrous oxide: a randomized, controlled, cross-over clinical trial. AB - OBJECTIVE: The purpose of this study was to investigate the effect of a portable video eyewear entertainment system used in conjunction with nitrous oxide/oxygen sedation during the removal of impacted lower third molars. STUDY DESIGN: Thirty eight patients had their bilateral third molars removed under local anesthesia and nitrous oxide/oxygen inhalation sedation in 2 visits. On one side, video eyewear was used (group NE). On the other side, the tooth was removed without the use of video eyewear (group N). Vital signs were monitored. Overall behavior and the outcome of treatment were assessed. RESULTS: All 38 patients completed the study. The mean scores on behavior rating in group NE were significantly higher than those in group N (P < .05). The majority of patients (92.1%) preferred nitrous oxide with video eyewear. CONCLUSIONS: The use of video eyewear appeared to augment the effectiveness of nitrous oxide sedation in dental extraction patients. PMID- 22677736 TI - Virtual model surgery and wafer fabrication using 2-dimensional cephalograms, 3 dimensional virtual dental models, and stereolithographic technology. AB - Although several 3-dimensional virtual model surgery (3D-VMS) programs have been introduced to reduce time-consuming manual laboratory steps and potential errors, these programs still require 3D-computed tomography (3D-CT) data and involve complex computerized maneuvers. Because it is difficult to take 3D-CTs for all cases, a new VMS program using 2D lateral and posteroanterior cephalograms and 3D virtual dental models (2.5D-VMS program; 3Txer version 2.5, Orapix, Seoul, Korea) has recently been introduced. The purposes of this article were to present the methodology of the 2.5D-VMS program and to verify the accuracy of intermediate surgical wafers fabricated with the stereolithographic technique. Two cases successfully treated using the 2.5D-VMS program are presented. There was no significant difference in the position of upper dentition after surgical movement between 2.5D-VMS and 3D-VMS in 18 samples (less than 0.10 mm, P > .05, Wilcoxon signed rank test). The 2.5D-VMS can be regarded as an effective alternative for 3D-VMS for cases in which 3D-CT data are not available. PMID- 22677737 TI - Complications in endoscopic-assisted open reduction and internal fixation of mandibular condyle fractures. AB - Endoscopic-assisted open reduction and internal fixation (EAORIF) of subcondylar fractures is minimally invasive, provides excellent visibility without a large incision, and reduces surgical scarring and the risk of facial nerve injury. This study evaluated the complications associated with EAORIF. Twenty-six patients underwent EAORIF for mandibular condyle fractures. The postoperative follow-up period was longer than 6 months. We analyzed associations between the complication incidence and the number of fixation plates, accompanying mandibular fractures, and age. Eighteen (69.2%) and 6 (23.1%) patients had temporary (<3 months after surgery) and long-term (>6 months after surgery) complications, respectively. Patients older than 30 years had complications more frequently than those younger than 30 years. Complication rates were similar for different numbers of fixation plates and among patients with and without accompanying mandibular fractures. EAORIF is a reliable technique for treating condylar fractures, regardless of patient age, number of fixation plates, or accompanying mandibular fractures. However, improvements are needed to reduce long-term complications. PMID- 22677738 TI - Management of 112 hospitalized patients with spreading odontogenic infections: correlation with DMFT and oral health impact profile 14 indexes. AB - OBJECTIVE: The aim of this study was to report our experience in treating patients affected by spreading odontogenic infections and to discuss their management and outcome. STUDY DESIGN: Demographic and clinical information was collected from hospitalized patient records. Decayed, missing, and filled teeth (DMFT) index was calculated for 45 randomly selected patients. Statistical analysis was used to search for associations among multiple variables. RESULTS: Statistical analysis of the variance by univariate test found significant associations between a longer hospital stay and patients >30 years old (P < .05) and patients with the presenting symptoms of dysphagia and/or dyspnea (P < .05). Statistical analysis using Fisher exact test found significant associations between patients with a DMFT index >10 and female patients (P < .05), patients >30 years old (P < .005), and a hospital stay >4 days (P < .0005). CONCLUSIONS: Rapid resolution of the infection was appreciated when removal of the cause, drainage of the infection, and intravenous antibiotics were performed. PMID- 22677739 TI - Intraoperative biopsy of the major cranial nerves in the surgical strategy for adenoid cystic carcinoma close to the skull base. AB - OBJECTIVE: Adenoid cystic carcinoma of the salivary glands has a propensity for perineural invasion, which could favor spread along the major cranial nerves, sometimes to the skull base and through the foramina to the brain parenchyma. This study evaluated the relationship between neural spread and relapse in the skull base. STUDY DESIGN: During surgery, we performed multiple biopsies with extemporaneous examination of the major nerves close to the tumor to guide the surgical resection. RESULTS: The percentage of actuarial local control at 5 years for patients with a positive named nerve and skull base infiltration was 12.5%, compared with 90.0% in patients who were named nerve-negative and without infiltration of the skull base (P = .001). CONCLUSIONS: Our study shows that local control of disease for patients who are named nerve-positive with skull base infiltration is significantly more complex compared with patients who are named nerve-negative without infiltration of the skull base. PMID- 22677740 TI - The impacted maxillary canine: a proposed classification for surgical exposure. AB - OBJECTIVE: One of the treatment options for the impacted maxillary canine is surgical exposure followed by orthodontic forced eruption. Several surgical techniques have been introduced in the literature for the exposure of the impacted canine. The aim of this study was to review the current literature and to introduce a classification for maxillary canine impactions that includes guidelines for selecting the proper surgical approach. METHODS: Epidemiology of canine impaction, diagnosis, and surgical options for the exposure of an impacted maxillary canine are discussed based on the current literature. RESULTS: Careful clinical examination and proper diagnostic imaging should be used to define the anatomical position of the impacted canine. The surgical approach for exposure of impacted maxillary canines should consider the anatomical position of the tooth in relation to the alveolar ridge and the amount of keratinized mucosa/gingiva. CONCLUSIONS: The proposed clinical classification provides a structured approach to treatment based on impacted tooth location and anatomical factors. PMID- 22677741 TI - Pseudotumor of hemophilia in the mandible of a patient with hemophilia A. AB - Hemophilic pseudotumor is a rare lesion that is essentially a progressive, slowly expanding, encapsulated hematoma. It is estimated to affect 1% to 2% of severe hemophiliacs. The majority of hemophilic pseudotumors occur within soft tissues (intramuscular) and long bones of adult males. Fewer than 20 cases have been reported in the maxillofacial region. We report a rare case occurring in the mandible of a 14-year-old boy who presented with considerable expansion and displacement of teeth. PMID- 22677743 TI - Increased expression of CK8 and CK18 in leukoplakia, oral submucous fibrosis, and oral squamous cell carcinoma: an immunohistochemistry study. AB - OBJECTIVE: Oral squamous cell carcinoma (OSCC) may be preceded by potentially malignant disorders such as leukoplakia and oral submucous fibrosis (OSF) and has a greater than normal risk of malignant transformation. Very little is known of cytokeratin (CK) alterations in OSF, leukoplakia, and OSCC. The aim of this study was to evaluate and compare the expression of CK8 and CK18 in normal oral mucosa, oral epithelial dysplasia, OSF, and OSCC by immunohistochemistry. STUDY DESIGN: Paraffin-embedded normal (n = 10), dysplasia (n = 10), OSF (n = 10), and OSCC (n = 10) tissues were stained with CK8 and CK18 by immunohistochemistry. RESULTS: Increased expression of CK8 and CK18 was seen in dysplasia, OSF, and OSCC. Staining pattern and intensity showed variations, with intensity of staining in basal and suprabasal layers for CK8 and CK18. CONCLUSIONS: Intensity of staining in the basal layer for CK18 was statistical significant, suggesting CK8 and CK18 as surrogate markers of malignant transformation. PMID- 22677742 TI - Adhesion molecule L1 is down-regulated in malignant peripheral nerve sheath tumors versus benign neurofibromatosis type 1-associated tumors. AB - Type 1 neurofibromatosis (NF-1), also known as von Recklinghausen disease, is caused by a disorder of a single gene on chromosome 17 that usually restrains cell division. A sequence that is frequently associated with NF-1 is tumor progression from neurofibromas to malignant peripheral nerve sheath tumors (MPNSTs). The aim of this study was to determine the expression of the neural L1 cell adhesion molecule in dermal-diffuse neurofibromas, plexiform neurofibromas, and MPNSTs of NF-1. We retrospectively analyzed surgically resected primary tumors, including 20 dermal neurofibromas, 23 plexiform neurofibromas, and 17 MPNSTs, by immunohistochemistry in paraffin sections of NF-1 tumors with the use of the L1-specific monoclonal antibody UJ127, which does not cross-react with other members of the L1 family. Immunostainings for CD34 and S100 were included to distinguish and allocate L1-expressing Schwann cells and perineural (specialized) fibroblasts. Our data showed that L1 is highly expressed in all benign NF-1 tumors and in some but not all MPNSTs. Furthermore, we demonstrated a correlation between L1 expression and differentiation grade of MPNSTs. There was a significant trend toward lower or nondetectable expression in the poorly differentiated MPNSTs, in contrast to all other tumor entities so far investigated, in which L1 expression correlated positive with malignancy, except for juvenile but not adult-derived neuroblastomas. Future studies are warranted to elucidate the molecular basis of the varying effects of the degree of L1 expression, receptor, and signal transduction mechanisms in different tumors. PMID- 22677744 TI - Three-dimensional assessment of impacted canines and root resorption using cone beam computed tomography. AB - OBJECTIVE: The objective of this study was to localize impacted canines in 3 dimensions and determine the most common location of impaction using cone beam computed tomography (CBCT). We also assessed root resorption of adjacent teeth. The cusp tip of each impacted canine was located and digitized using Dolphin 3D imaging, after viewing sagittal, coronal, and axial views. The position on the occlusal plane where the normally erupted canine cusp tip should be located was used as a control reference point. The degree of impaction was defined by the difference between the impacted canine cusp tip and reference cusp tip positions. MATERIALS AND METHODS: CBCT scans of 29 consecutive individuals with impacted canines undergoing orthodontic treatment at the UCSF Orthodontic Clinic were included in this study. RESULTS: The average degree of mesial impactions was 10.1 mm, of distal impactions was 4.2 mm, of facial impactions was 4.16 mm, of palatal impactions was 1.8 mm, and of gingival impactions was 10 mm; 40.4% had no root resorption, 35.7% showed slight root resorption, 14.2% showed moderate resorption, and 4% showed severe root resorption of the adjacent lateral incisor. CONCLUSION: We reliably assessed the position of impacted canines in 3 dimensions using CBCT, thereby improving accuracy of location and facilitating precise surgical and orthodontic management. In our study 40.4% had no root resorption, 35.7% showed slight root resorption, 14.2% showed moderate resorption, and 4% showed severe root resorption of the adjacent lateral incisor. The most frequent location of impacted canines was palatal, mesial, and gingival. PMID- 22677745 TI - Clinical and radiological presentation of hemimaxillofacial dysplasia/segmental odontomaxillary dysplasia: critical analysis and report of a case. AB - OBJECTIVES: The purpose of the present study was to critically evaluate the literature, describe the clinical and radiographic features of HD-SOD (hemimaxillofacial dysplasia/segmental odontomaxillary dysplasia), and describe one new case, involving a 12-year-old boy, with detailed radiological, clinical, and histologic characteristics. METHODS: Thirty-six cases published between 1987 and 2010, together with the present case, were evaluated according to criteria that included gender, age, location of the lesion, findings, and symptoms. RESULTS: We found that the lesion is discovered mainly in the first decade of life (71%), and has a male predilection (64%, 23/64). The maxillary alveolar process was affected unilaterally in all cases, with gingival and bone enlargement and facial asymmetry being constant findings. Missing premolars and skin manifestations were found to be common features. CONCLUSIONS: New case reports should include clinical, radiographic, and histologic findings; follow-up reports; and treatment protocols to improve dentist and parent information regarding HD. PMID- 22677746 TI - Glutathione peroxidase 1 Pro198Leu polymorphism in Brazilian Alzheimer's disease patients: relations to the enzyme activity and to selenium status. AB - BACKGROUND/AIMS: Oxidative stress plays a central role in Alzheimer's disease (AD). Pro198Leu cytosolic glutathione peroxidase (GPx1) polymorphism seems to be associated with a lower activity of this enzyme, but there are no studies with AD patients. Thus, the aim was to determine the frequency of the GPx1 Pro198Leu polymorphism in AD patients and to verify its relation to glutathione peroxidase (GPx) activity and selenium (Se) status. METHODS: The study was carried out in a group of AD elderly (n = 28) compared to a control group (n = 29). Blood Se concentrations were measured through hydride generation atomic absorption spectroscopy. GPx activity was determined using a commercial kit, and the polymorphism using amplified DNA sequencing. RESULTS: The distribution of genotypes was not different between groups. The variant allele frequency was 0.179 (AD group) and 0.207 (control group). Although no differences regarding GPx activity were found between individuals with different genotypes, lower blood Se levels were found in Pro/Pro AD patients compared to Pro/Pro control subjects, which was not found in the Pro/Leu groups. Moreover, the association between the erythrocyte Se concentration and GPx activity was affected by the Pro198Leu genotype. CONCLUSIONS: Results indicate that this polymorphism had apparently affected Se status in AD patients and that more studies in this field are necessary. PMID- 22677747 TI - Meta-analysis of neurodevelopmental outcome after room air versus 100% oxygen resuscitation: generating more questions than answers?. Commentary on O.D. Saugstad et al.: neurodevelopmental outcome of infants resuscitated with air or 100% oxygen: a systematic review and meta-analysis (Neonatology 2012;102:98-103). PMID- 22677748 TI - [The diagnosis of brain death: the current state of the problem]. PMID- 22677749 TI - [EEG changes in patients undergoing on-pump coronary artery bypass grafting]. AB - We studied the changes of electroencephalograms (EEG) related to on-pump coronary artery bypass grafting (CABG) in 28 right-handed male patients with coronary heart disease (CHD), 10 from which had accompanying moderated (30-50%) carotid artery (CA) stenoses. All EEG studies were performed 3-5 days before and 7-11 days after CABG. EEG data of healthy age-matched males (n=14) were examined. Before surgery, the CHD patients differed from the control group by less expressed theta2 and beta1 rhythm power asymmetry. The differences demonstrated worse conditions for cognitive processes in CHD patients. After CABG, the higher power of teta1 and 2 rhythms, predominantly in the frontal lobe of the left hemisphere which was mostly expressed in patients with CA stenosis, was observed in all CHD patients. This effect can be considered as the appearance of ischemic neuronal injury caused by on-pump CABG. The localization of changes in the frontal cortex of the left hemisphere can be related to a high vulnerability of these regions. The deficit of cerebral blood flow in these regions will define a clinical picture of cognitive decline after CABG. PMID- 22677750 TI - [Clinical typology of atypical depression in bipolar and unipolar affective disorders]. AB - Forty-six patients with the DSM-IV diagnosis of atypical depression have been examined using clinical-psychopathological and psychometric methods. Based on prevailing symptoms, three types of atypical depression have been singled out: atypical depression with mood reactivity, atypical depression with inverted autonomous symptoms and atypical depression with rejection sensitivity. Sociodemographic and clinical characteristics of each variant are presented and their representation in the structure of bipolar and unipolar depressive disorder is determined as well. PMID- 22677751 TI - [The use of cerepro (choline alfoscerate) in the treatment of outpatients with chronic progressive cerebrovascular disease]. AB - The main aim of the study was the evaluation of the efficacy and drug safety of cerepro (choline alfoscerate) used for treating outpatients with cerebrovascular disease. Ninety patients with cerebrovascular disease, who had motor, coordination, emotional and cognitive disturbances were enrolled in the study. Sixty patients of the group 1 had stroke, 30 patients (group 2) had chronic ischemic brain disease. All patients received basic therapy (antihypertensive, antiaggregant or anticoagulant, cholesterol-lowering drugs). Cerepro was administrated in combined therapy according to the scheme: 1000 mg cerepro (in 200 ml of the 0.9% NaCl solution) once a day intravenously in drops during 10 days; then 1200 mg daily per os during 6 weeks. We assessed the dynamic of neurological symptoms and restoration of lost functions (MMSE, Feeling-activity mood test, HDRS, GCI). The results indicate the efficacy of cerepro in outpatients with chronic cerebrovascular disease and stroke. It was demonstrated that cerepro led to improvement of coordination neurological symptoms, cognitive and emotional functions, activity and mood in patients of both groups. Clinical effect was higher in patients after stroke. Cerepro was well tolerated. PMID- 22677752 TI - [Interferon status in the treatment of neuroleptic-resistant patients with paranoid schizophrenia]. AB - We studied 73 patients with paranoid schizophrenia with resistance to neuroleptics. All patients were divided into two groups - basic (37 patients) and comparison (36 patients). Both groups received traditional treatment. Patients of the basic group were treated with the combination of reamberin and cycloferon. Before treatment, significant alterations in the interferon status (IFS), which were characterized by the decrease of serum interferon (SIFN) activity and blood alpha- and gamma-interferons (IFN) levels, were identified in both group. The positive effect of the drug combination on clinical symptoms and interferon status (the normalization of SIFN activity, increase in blood alpha- and gamma IFN levels) was found. PMID- 22677753 TI - [Transcranial magnetic electro-stimulation with alternate action on brain hemispheres in the correction of cerebral disturbances in children with diabetes mellitus type 1]. AB - Correction of psychoemotional and autonomic disturbances in children 7-17 years old with diabetes mellitus type 1 was conducted using transcranial magnetic electro-stimulation with alternate action on brain hemispheres (main group, 42 patients). The method includes the combined action of magnetic field pulses and series of electric impulses; magnetic and electric stimulation were performed synchronously - at first, on one brain hemisphere, then on another hemisphere with alternation frequency 9.5-10.5 Hz. A comparison group consisted of 44 patients with diabetes mellitus type 1 who received physiotherapeutic treatment as a combination of transcranial magnetic therapy and electro-stimulation with simultaneous action on both brain hemispheres. Treatment duration was 10 sessions. Treatment efficacy was assessed by the decrease in frequency and intensity of complaints, improvement of patient's health status measured (a scale for assessment of activity, health perception and mood) and improvement of the status of the autonomic nervous system (Vein's questionnaire), mental sphere (the Luscher color test) and cognitive traits (The Concentrated Attention Test of the Toulouse-Pierron Factorial Battery). The status of the autonomic nervous system was evaluated before and after the treatment using cardiointervalography. Brain bioelectrical activity was assessed using encephalography. Significant reduction of autonomic, psychoemotional and cognitive disturbances, normalization of brain bioelectrical activity due to the alpha-rhythm organization and arrhythmia removal were identified in the main group after the treatment. No adverse effects of this physiotherapeutic treatment was found. PMID- 22677754 TI - [Pantogam and pantogam active: qualitative and quantitative features of the interaction with neurotransmitter receptors in vitro]. AB - We conducted a comparative study on the effect of active compounds of pantogam and pantogam active (calcium D(R)-homopantothenate and calcium DL(RS) homopantothenate) and its L(S)-isomer on the receptors of main brain neuromediators in rats using in vitro radioligand binding analysis. All three compounds interact with binding sites of specific GABA-A and, in particular, GABA B receptor ligands. Racemate and S-enantiomer, but not its R-form, competed to a moderate degree for D2-receptor binding sites. In all cases, degrees of interaction with receptors were ranged as follows: S-isomer>racemate>R-isomer. These qualitative and quantitative differences are assumed to contribute to pharmacological activity of both drugs. PMID- 22677755 TI - [Adaptogenic effects of mexidol in chronic cerebral ischemia]. AB - The data on the effect of the succinate-containing antioxidant mexidol on the adaptation abilities of patients with chronic brain ischemia are presented. We studied 98 patients with discirculatory encephalopathy of I, II and III stages. A set of indices for psychoemotional status, functional state of the brain, autonomic status, nonspecific stability to hypoxia, adaptive reactions of the blood system and status of antioxidant defense have been used to evaluate adaptive abilities of the body. It has been shown that the introduction of the antioxidant in the treatment set strengthens the effects of basic treatment by increasing adaptive reserves of the body in stages I and II of disease that is related with the realization of reactions of urgent adaptation. The introduction of mexidol in the treatment set increases the frequency of favorable outcomes after one year of follow-up. PMID- 22677756 TI - [The patterns of interzonal EEG relations and its relationship with the subjective assessment of single-dose action of phenazepam in patients with anxiety disorders]. AB - The spectral-coherence analysis of phenazepam single-dose action in patients with anxiety disorder was performed. Significant changes in coherence parameters indicating the generalized character of reorganizations of interzonal connections with the involvement of delta, alpha, theta and beta-1 to beta-3 rhythms, including both their strengthening and weakening, were revealed. Correlations between the character of reorganizations of interzonal relations and subjective assessments of the drug effect were observed: activating and antianxiety drug effects were correlated with tolerability and the wish to continue treatment with the drug. Results suggest that drug effect on EEG spectra is more informative when subjective assessments are taken into account. PMID- 22677757 TI - [Association of blood serum biochemical markers with neurologic syndromes in the exacerbation of dorsolumbar osteochondrosis]. AB - The content of C-reactive albumin (CRA) and endothelin-1 in patients with neurologic syndromes of dorsolumbar osteochondrosis (lumbodynia, lumboischialgia, lumbosacral radiculopathy) during exacerbation was investigated. CRA concentration in blood serum was determined by a highly sensitive quantitative method (in the interval from 0.1 g/l), based on the reaction of immunoprecipitation. Endothelin-1 content in the blood serum was determined by means of immunoenzymometric analysis method. The statistically significant (p<0,05) increase in concentrations of C-reactive albumin and endothelin-1 in the peripheral blood serum was found in 43 patients with lumbosacral radiculopathy compared to the control group and groups of patients with syndromes of lumbodynia and lumboischialgia. The direct correlation (r=0,71; p<0,01) between the content of CRA and endothelin-1 in the peripheral blood serum in patients with lumbosacral radiculopathy was established. PMID- 22677758 TI - [Clinical and epidemiological aspects of multiple sclerosis in the Moscow region]. PMID- 22677759 TI - [Neuroleptics in the treatment of schizophrenia spectrum disorders (a pharmacoepidemiological outpatient study)]. PMID- 22677760 TI - [Characteristics of the autonomous control of cardiac activity in patients with remitting multiple sclerosis]. PMID- 22677761 TI - [Dynamics of perfusion CT parameters in the early acute phase of ischemic stroke]. AB - Perfusion computed tomography (CT) allows to evaluate brain perfusion and provides additional information about local cerebral hemodynamics in stroke patients. Twenty-seven patients underwent CT-perfusion in the early acute phase of ischemic stroke. Significant differences between ischemic lesion and contralateral hemisphere on CBF and MTT scans during the first 3 hours after stroke were revealed. In the following 24 h, the differences were seen in all perfusion parameters. CT-perfusion allows to reveal perfusion parameters associated with stroke severity and outcome that is relevant for prescription of reperfusion treatment beyond the boundaries of 3-4.5h "therapeutic window". PMID- 22677762 TI - [Intensive glycemia control in the first day of the acute cerebral blood flow disturbance in patients with diabetes mellitus type 2]. AB - Forty-seven patients with cerebral stroke and diabetes mellitus type 2 were included in the study. To maintain the target values of glycemia on the level 7.8 10.2 mmol/l, patients of the main group received the continuous intravenous infusion of insulin and patients of the control group received frequent (every 3h) subcutaneous injections of insulin during the first 24 h after the acute cerebral blood flow disturbance. The results obtained have shown that continuous intravenous insulin infusion reduces the risk of hypoglycemia, accelerates positive neurologic dynamics, reduces terms of hospitalization and decreases mortality in patients with diabetes mellitus type 2. PMID- 22677763 TI - [Efficacy of cereton in acute ischemic stroke: results of the trial SOLNTSE]. AB - We studied 95 patients with acute (no later than 24h after onset) carotid ischemic stroke. Patients of the main group (50 patients) received cereton in dose 4 ml (1000 mg) intravenously during 10 days in the combination with traditional treatment; 45 patients of the control group received only traditional treatment. Neurological deficit on NIHSS and vigilance on The Glasgow Coma Scale were assessed at baseline and in 5th, 7th and 19-21th days. The Barthel index was used to measure functional independence of the patient at the discharge from a hospital (21th day). The "cost-effectiveness" ratio, the cost of one score on the NIHSS and Barthel scales were calculated. The reduction in neurological deficit (p<0.05) and higher extent of functional independence were seen in the main group compared to the controls. Based on the "cost-effectiveness" analysis, the use of cereton was shown to be more effective for treatment of patients with acute ischemic stroke: the cost of the achievement of positive effect in patients of the control group receiving only traditional treatment was significantly higher (p<0.05). PMID- 22677764 TI - [Evaluation of factors determining the efficiency of kinesotherapy in acute ischemic stroke patients]. AB - The aim of this paper was to evaluate factors influencing the efficiency of kinesotherapy in acute ischemic stroke patients during the first rehabilitation stage. Forty patients with stroke, aged between 45 and 74 years, were enrolled in the study. The individual kinesotherapy of 30-45 minutes duration was applied for stroke patients 5 times a week. The efficiency of kinesotherapy was assessed by the modified Functional independence measure scale and the Motor assessment scale before and after treatment. Information about patient's gender, age, weight, brain lesion localization, stroke localization, the depth of lesion, aphasia, number of comorbidities, the beginning of kinesotherapy, patient's motivation and family member participation in the rehabilitation was taken according to a research protocol. The motor function of stroke patients significantly (p<0.05) improved after kinesotherapy sessions at the end of the first stage of rehabilitation. The lower efficiency (p<0.05) of kinesotherapy for acute stroke patients was determined by the brain lesion localization in the left hemisphere and middle cerebral artery, hemiplegia, sensomotor aphasia, and low motivation of the patient. PMID- 22677765 TI - [Neuroprotective treatment with citicoline (ceraxon) in patients with ischemic stroke]. AB - The dynamics of neurological symptoms assessed with the Scandinavian stroke scale, the Barthel index and the modified Rankin scale was studied in 89 patients with moderate ischemic stroke who received citicoline (ceraxone) intravenously and orally. The results were compared to a group of 52 age-, sex- and stroke matched patients who did not receive citicoline. To the date of discharge from the hospital (days 21-24), the full restoration (p<0.05) was noted in patients of the main group. Efficacy of citicoline was significantly (p<0.05) higher in patients younger than 70 years and when the drug was used in the first hours of disease. PMID- 22677766 TI - [Efficacy of adepress (paroxetine) in the treatment of depression in patients with chronic cerebral ischemia in the late recovery phase of ischemic stroke with the estimation of the velocity of passive transmembrane ion transport]. AB - We studied the correlation between the efficacy of adepress (paroxerine) and the state of cell membranes assessed by the velocity of passive transmembrane ion transport in 39 patients (20 patients with chronic brain ischemia and 19 patients with ischemic stroke). Velocity of passive transmembrane ion transport estimated by the level of Na+-Li+ counter-transport (NLC) in the erythrocyte membrane was a criterion of the cell membrane functional activity. The higher the NLC velocity, the more severe was the course of depression with the development of cognitive dysfunction and pain syndromes in patients with chronic brain ischemia and stroke. At the same time, the higher clinical efficacy of adepress (paroxerine) was seen in patients with higher NLC velocities. Estimation of NLC velocity in the erythrocyte membrane may be used for identification of risk groups for the development of affective disorders in patients with stroke and chronic brain ischemia as well as for prediction of treatment efficacy. PMID- 22677767 TI - [Changes in the hemostasis system and free-radical lipid oxidation in the acute stage of ischemic stroke in patients on neuroprotection treatment]. AB - We examined 163 patients with primary ischemic stroke admitted within the first 12 h after stroke onset. Neurological status on the Orgogozo scale and blood test results (lipid spectrum, level of free-radical lipid oxidation measured with chemiluminescent method, hemostasis system parameters) were estimated at admission and on the 21th day of stroke. Patients were stratified into 3 groups: group 1 (n=59) received traditional treatment and mexidol during the first 10 days in dose 500,0 mg intravenously and cerebrolysate in dose 1,0 ml intramuscular; group 2 (n=60) received cerebrolysate in dose 1,0 ml intramuscular during 10 days in addition to traditional treatment; group 3 (n=44) received only traditional treatment. At baseline, patients with ischemic stroke demonstrated the increase in blood plasma atherogenicity (p<0,05), intensity of free-radical lipid oxidation and thrombogenic potential of blood that were correlated with disease severity. Administration of neuroprotective drugs mexidol and cerebrolysate in addition to complex treatment of stroke improved the lipid spectrum, reduced the intensity of free-radical lipid oxidation, stabilized hemostasis parameters. The increase in survival rate and more rapid reversal of neurological deficit in patients of group 1 were identified to the 21th day. PMID- 22677768 TI - [The association between the DNA marker rs1842993 and risk for cardioembolic stroke in the Slavic population]. AB - The analysis of association between DNA markers and total stroke risk was performed in 950 Slavonic patients. Patients with cardioembolic stroke were selected for a genome-wide association study. The HUMANCYTOSNP12 v.2 microchip was used to analyze all DNA samples on a panel of 301 000 single nucleotide polymorphisms. SNP rs1842993 on chromosome 7 was found to be associated with cardioembolic stroke risk. PMID- 22677769 TI - [Analysis of a disturbance of trace element balance in patients with ischemic stroke with arterial hypertension]. AB - Disturbance of trace element balance increases the risk of cerebrovascular disease and, above all, ischemic stroke (IS). A comparative analysis of clinical and demographic parameters and trace element composition of hair was performed in the group of 30 ischemic stroke patients with arterial hypertension (AH) and 30 stroke patients without hypertension (mean age 55+/-7 years). The stroke patients with hypertension were characterized by the elevated body mass index (28.5+/-4.1 kg/m2, AI, 26.0+/-2.9 kg/m2, p=0.006), higher incidence of coronary heart disease (p=0.04). Alcohol consumption more than 3 drinks a week was associated with a 5 fold increase of the risk of stroke with hypertension (95% CI 1.0-27, p=0.035). The results revealed a number of statistically significant differences in trace element profile in the studied groups of patients: deficits of essential magnesium, manganese, cobalt, copper, zinc, a statistically significant increase in sodium levels, toxic and conditionally toxic trace elements (cadmium, mercury, bismuth, barium, etc.). One of the probable factors that lead to the accumulation of toxic trace elements in stroke patients is the increased consumption of alcohol including that of substandard quality. The data obtained also show the feasibility of implementing screening programs to assess micronutrient status (including trace elements) for early detection of pathological abnormalities in the elemental homeostasis that might lead to an increased risk of ischemic stroke and hypertension. PMID- 22677770 TI - [Stroke incidence and mortality in the North Easten region of Azerbaijan Republic]. AB - The research objective consisted in studying 10-year (1999-2008) dynamics of incidence and mortality rate of stroke in the northeast region of Azerbaijan. All cases of stroke in the region have been retrospectively studied. The 10-year chronological average level of incidence of stroke was 1.2+/-0.050/00, the mortality rate from a stroke was 0.4+/-0.030/00. Among all strokes, 67.5+/-0.6% was ischemic stroke, 18.3+/-0.5% was hemorrhagic stroke and 5.3+/-0.3% subarachnoid hemorrhage. It was not possible to specify the type of stroke in 9.0+/-0.4% of cases. A trend towards lower incidence of a stroke in the region in 1999-2008 was noted. Survival after the stroke has averaged 2.08 years and didn't change significantly in 1999-2008. On average, 1/3 patients with stroke die within a year. The indicator of annual mortality in 1999-2008 showed no statistically significant changes, with interval 31.5+/-1.7-37.2+/-2.2%. PMID- 22677771 TI - Cloned tomato golden mosaic virus back in tomatoes. AB - Clones of tomato golden mosaic virus (TGMV), a key model for geminivirus research, have been transmitted back to their original host tomato for the first time. In contrast to the high pathogenicity in other solanaceous species, TGMV induced only very mild symptoms: a few chlorotic spots on the leaf lamina for the common variant (formerly strain cs), and limited vein yellowing for the yellow vein variant (yv). Symptoms disappeared over time, though viral DNA remained detectable in newly developed leaves. Both TGMV variants invaded phloem and, occasionally, also mesophyll parenchyma cells in tomato. Complete direct sequencing of rolling circle amplification products of the viral progeny in tomato plants revealed the consensus of the DNA populations for the two genome components (DNA-A, DNA-B) of both TGMV variants. The DNA-A components showed 98.5% and 99.9% nucleotide sequence identity, respectively, with the independently cloned TGMV molecule sequenced initially in 1984, confirming the classification of csTGMV and yvTGMV as variants. The results are discussed with reference to the history of the Brazilian "mosaico dourado" disease in tomato, and the odyssey of TGMV passaging through Nicotiana benthamiana plants and bacteria of numerous laboratories worldwide. PMID- 22677772 TI - Stimulation of Hepatitis C Virus RNA translation by microRNA-122 occurs under different conditions in vivo and in vitro. AB - Translation of the Hepatitis C Virus (HCV) positive strand RNA genome is directed by an internal ribosome entry site (IRES) in the viral RNA's 5'-untranslated region (5'-UTR). HCV propagates preferentially in the liver, and HCV translation is stimulated by the liver-specific microRNA-122 (miR-122) acting on two target sites in the 5'-UTR. This stimulation is effective in living cells containing miR 122 and also in the rabbit reticulocyte lysate in vitro-translation system after addition of miR-122. Another RNA sequence located in the Core protein coding sequence can base-pair in a long-range RNA-RNA interaction to the HCV 5'-UTR, overlapping with the miR-122 target sites and the short spacer between them, and thereby inhibits HCV translation. Here we show genetic evidence that in reticulocyte lysate single-stranded miR-122 interferes with this inhibitory long range RNA-RNA interaction and thereby contributes to enhanced HCV translation, involving not only the 5'-seed sequence of miR-122 but also sequences at its 3' end. Also RNA oligonucleotides shorter than a typical microRNA stimulate HCV translation, confirming that in the reticulocyte lysate the stimulation of HCV translation functions by displacement of the inhibitory long-range interaction by miR-122. In contrast, in transfected HuH-7 hepatoma cells and in HeLa cells this interference of miR-122 with the inhibitory long-range RNA-RNA interaction plays not a major role, but only duplex miR-122 RNAs of the correct length stimulate HCV translation. These results suggest that: (1) the processing of the microRNA precursors and (2) the events occurring at the HCV RNA differ between cells and reticulocyte lysate. PMID- 22677773 TI - Identification of the bacteriocin subtilosin A and loss of purL results in its high-level production in Bacillus amyloliquefaciens. AB - A mini-Tn10 transposon mutagenesis library of strain Bacillus amyloliquefaciens BAhja NK10 was constructed and one mutant, L4, exhibiting markedly enhanced antagonistic activity against Micrococcus luteus, was screened and possessed an inactivated purL gene. A similar antibacterial spectrum was observed for both L4 and wild-type strains, but L4 displayed a markedly strengthened antimicrobial effect. Extracts of the corresponding culture media were separated by means of liquid chromatography and subjected to antimicrobial assay wherein the active molecule was further purified. Mass spectrometry and genetic analysis data revealed that the bacteriocin subtilosin A was produced and was responsible for the antibacterial activity of B. amyloliquefaciens. Expression of the subtilosin A-encoding gene sboA was determined to occur earlier in the purL mutant, while the transcription level of the negative regulator AbrB declined by 3.3-fold. Correspondingly, an increase was observed in the mRNA levels of two early sporulation genes spo0A and sigH, which are implicated in repressing abrB expression and regulating subtilosin A production. Moreover, RT-PCR showed that the expression of three Kin family kinases was coordinately upregulated. We speculated that purL mutation could result in induced expression of Kin kinases and accelerated accumulation of phosphorylated Spo0A, with the latter repressing transcription of abrB which ultimately led to earlier and increased production of the bacteriocin subtilosin A. PMID- 22677774 TI - A positive selection approach identifies residues important for folding of Salmonella enterica Pat, an N(epsilon)-lysine acetyltransferase that regulates central metabolism enzymes. AB - In Salmonella enterica, the protein acetyltransferase (Pat) enzyme is part of the sirtuin-dependent acylation/deacylation system (SDPADS) that modulates the activity of several proteins via the acylation of lysine residues critical to their activities. Pat is a ~98 kDa protein with two distinct domains, an N terminal acyl-CoA synthetase (NDP-forming) domain (~700 aa) and a C-terminal acetyltransferase domain (~160 aa), with homology to proteins of the Gcn5-related N-acetyltransferase (GNAT) superfamily. Although the role of the GNAT-like domain is likely responsible for the catalytic activity of Pat, the role of the N terminal domain remains unclear. Here we report the use of positive selection for identification of residues critical for Pat enzyme activity. This approach revealed seven residues that, when changed, resulted in drastic loss of Pat activity in vitro which caused a discernable loss-of-function phenotype. Five of the seven residues were located in the N-terminal region of Pat and two were located in the GNAT-like domain. Each single-amino-acid variant had a circular dichroism spectrum that differed from that of the wild-type Pat protein, suggesting that loss of enzymatic activity in the mutant proteins was likely due to an inability to acquire its biologically active fold. PMID- 22677775 TI - Herpes zoster in patients treated with biologicals. AB - BACKGROUND: The incidence and severity of herpes zoster (HZ) appear increased in patients receiving tumor necrosis factor-alpha antagonists. OBJECTIVE: To study the incidence and clinical features of HZ in 1,220 patients (4,206 patient-years) receiving either adalimumab, etanercept, infliximab, rituximab or ustekinumab. RESULTS: Twenty-two HZ cases were identified [1.26% of total cohort; adalimumab: 11/1,546 patient-years, incidence rate (IR) 7.1; etanercept: 4/789 patient-years, IR 5.1; rituximab: 1/168 patient-years, IR 5.2; ustekinumab: 2/37 patient-years, IR 53.5; infliximab: 4/1,666 patient-years, IR 2.4]. The time to event varied widely (1.5- 108 months). Extensive HZ was reported in 45 and 32% of the cases, respectively. Persistent postzoster neuralgia (PHN; >6 months) was observed in 5/20 patients. CONCLUSIONS: The HZ incidence was 2.1-fold higher among patients over 60 years, compared with a reference population, although not statistically significant. Severe, multidermatomal HZ and persistent PHN were common. PMID- 22677776 TI - Current world literature. PMID- 22677778 TI - Extended NO analysis in health and disease. AB - Extended NO analysis is a promising tool in different diseases where NO metabolism is altered. One single exhalation cannot give insight to the NO production in the respiratory system; rather the use of multiple exhalation flows can give the alveolar levels (C(A)NO), airway wall concentration (C(aw)NO) and the diffusion rate of NO (D(aw)NO). Increased values of C(A)NO are shown in COPD, systemic sclerosis, hepatopulmonary syndrome and in severe asthma. In asthma the C(aw)NO and D(aw)NO are increased leading to an increase in bronchial NO flux (J'(aw)NO). Low levels of J'(aw)NO are seen in cystic fibrosis, primary ciliary dyskinesia and in smoking subjects. More studies are needed to evaluate the clinical usefulness of the extended NO analysis, similar to what has been done in systemic sclerosis where a cut-off value has been identified predicting pulmonary function deterioration. PMID- 22677779 TI - Photochemical properties of a myoglobin-CdTe quantum dot conjugate. AB - A myoglobin-cadmium telluride quantum dot conjugate was constructed using an artificial heme modified with a thiol moiety as a linker. Irradiation of the myoglobin-cadmium telluride conjugate generated the photoreduced ferrous myoglobin via an electron transfer from the photoexcited quantum dot, leading to the formation of CO-bound myoglobin under a CO atmosphere. PMID- 22677780 TI - Interleukin-6 -634G>C genetic polymorphism is associated with prognosis following surgery for advanced thoracic esophageal squamous cell carcinoma. AB - OBJECTIVE: Systemic and/or local interleukin-6 (IL-6) reportedly plays an active role in the progression and prognosis of thoracic esophageal squamous cell carcinoma (TESCC). We assessed the associations between IL-6 and IL-6 receptor (IL-6R) genetic polymorphisms, tumoral IL-6 expression and survival rates following surgery. METHODS: The study participants were 63 Japanese patients treated between 2003 and 2008 for T2-T4 advanced TESCC using curative esophagectomy without neoadjuvant treatment. We investigated IL-6 -634G>C (rs1800796) and IL-6R 48892A>C (rs8192284, Asp358Ala) genetic polymorphisms using DNA from peripheral blood samples. In addition, tumoral IL-6 expression was investigated immunohistochemically in resected specimens, and serum IL-6 was measured using a human IL-6 immunoassay. RESULTS: There was a significant difference in survival between patients with the IL-6 -634G/G+G/C genotype and those with the C/C genotype, such that their 5-year overall survival rates were 42 and 72%, respectively. By contrast, the IL-6R 48892A /C genotype and tumoral IL-6 expression had no significant effect on survival among patients. Univariate and multivariate analyses revealed that IL-6 -634G>C polymorphism was an independent prognostic factor with a hazard ratio of 3. CONCLUSIONS: IL-6 -634G>C genetic polymorphism may be a predictive prognostic factor in patients receiving esophagectomy for TESCC. PMID- 22677781 TI - Expression of the sodium/calcium/potassium exchanger, NCKX4, in ameloblasts. AB - Transcellular calcium transport is an essential activity in mineralized tissue formation, including dental hard tissues. In many organ systems, this activity is regulated by membrane-bound sodium/calcium (Na(+)/Ca(2+)) exchangers, which include the NCX and NCKX [sodium/calcium-potassium (Na(+)/Ca(2+)-K(+)) exchanger] proteins. During enamel maturation, when crystals expand in thickness, Ca(2+) requirements vastly increase but exactly how Ca(2+) traffics through ameloblasts remains uncertain. Previous studies have shown that several NCX proteins are expressed in ameloblasts, although no significant shifts in expression were observed during maturation which pointed to the possible identification of other Ca(2+) membrane transporters. NCKX proteins are encoded by members of the solute carrier gene family, Slc24a, which include 6 different proteins (NCKX1-6). NCKX are bidirectional electrogenic transporters regulating Ca(2+) transport in and out of cells dependent on the transmembrane ion gradient. In this study we show that all NCKX mRNAs are expressed in dental tissues. Real-time PCR indicates that of all the members of the NCKX group, NCKX4 is the most highly expressed gene transcript during the late stages of amelogenesis. In situ hybridization and immunolocalization analyses clearly establish that in the enamel organ, NCKX4 is expressed primarily by ameloblasts during the maturation stage. Further, during the mid-late maturation stages of amelogenesis, the expression of NCKX4 in ameloblasts is most prominent at the apical poles and at the lateral membranes proximal to the apical ends. These data suggest that NCKX4 might be an important regulator of Ca(2+) transport during amelogenesis. PMID- 22677782 TI - Unusual case of acute appendicitis with left upper quadrant abdominal pain. AB - INTRODUCTION: Acute appendicitis is one of the most frequent causes of surgical abdominal pain presenting to the Emergency Department. The diagnosis is confirmed by a set of clinical signs, blood tests and imaging. The typical presentation consists of periumbilical pain radiating to the right lower quadrant with peritoneal reaction on palpation (Mac Burney). PRESENTATION OF CASE: In this article, we report a case of acute appendicitis presenting with a left upper quadrant pain due to intestinal malrotation and we describe the radiologic findings on computed tomography. DISCUSSION: With an Alvarado score of 4 and a nonconclusive abdominal U/S, the diagnosis of acute appendicitis was a long shot. Persistence of pain and increasing inflammatory parameters in her blood exams pushed the medical team to further investigate and a CT scan revealed intestinal malrotation with acute appendicitis. CONCLUSION: An examining physician should not be mislead by the atypical presentation of acute appendicitis and should bear in mind the diagnosis to avoid serious complications. PMID- 22677783 TI - Effects of commercial formulations of deltamethrin and/or thiacloprid on thyroid hormone levels in rat serum. AB - Deltamethrin (DEL) and thiacloprid (THIA) are the two commonly used synthetic insecticides applied either separately or as a mixture. The aim of this study was to assess thyroid stimulating hormone (TSH) and the serum levels of thyroid hormones exposure to these compounds in rats. The animals were orally gavaged with a single dose of DEL (15 mg/kg), THIA (112.5 mg/kg) or DEL + THIA (15 + 112.5 mg/kg) for 24 h (acute treatments) or DEL (3 mg/kg per day), THIA (22.5 mg/kg per day) or DEL + THIA (3 + 22.5 mg/kg per day) for 30 days (subacute treatments). Although all independent and combined treatments with DEL and THIA changed the levels of TSH, these alterations were not significant. Statistically significant increases in free triiodothyronine (FT3) and free thyroxine (FT4) serum hormone levels were observed in the independent treatment with THIA and the combined treatment with DEL and THIA for 30 days. The results of this study suggest that in vivo exposure to subacute treatments of commercial formulations of THI and mixture of DEL + THIA increased serum FT3 and FT4 levels in rats. Further studies are required to determine the effects of endocrine disruptors and potential health risks of these insecticides in human, especially in children because of the importance of these hormones during growth and development. PMID- 22677784 TI - Effect of the direct renin inhibitor aliskiren in the prevention of experimental contrast-induced nephropathy in the rat. AB - BACKGROUND: Renal vasoconstriction, activated by the renin-angiotensin system, plays a pivotal role in the pathogenesis of contrast-induced nephropathy (CIN). The purpose of this study was to evaluate the effect of aliskiren, a direct renin inhibitor, for the prophylaxis of experimental CIN in the rat. METHODS: Thirty two Wistar albino rats were divided into four groups of 8 rats each, namely the control (C), aliskiren (A), contrast media (CM) and aliskiren plus contrast media (ACM) groups. Aliskiren was given orally at a dose of 50 mg/kg/day once daily for 5 consecutive days. CIN was induced by intravenous administration of indomethacin, N-nitro-L-arginine methyl ester and high-osmolar contrast medium meglumine amidotrizoate. Renal function parameters, kidney histology and tubular expression of vascular endothelial growth factor were determined. RESULTS: Mean serum creatinine was significantly lower (p < 0.001) and mean creatinine clearance was higher (p < 0.001) in the ACM group compared with the CM group. However, there were no differences between the ACM and CM groups in terms of tubular necrosis, proteinaceous casts, medullary congestion and vascular endothelial growth factor expression. CONCLUSION: Our preliminary data seem to suggest a potential role of aliskiren for the prophylaxis of CIN in an experimental rat model. PMID- 22677786 TI - Testicular tumor ultrasound characteristics and association with histopathology. AB - INTRODUCTION: This study was undertaken to develop knowledge of ultrasound characteristics of germ cell testicular neoplasms, associate these characteristics with histopathologic tumor types, and lay a foundation for study of ultrasound findings in benign versus malignant testicular lesions. MATERIALS AND METHODS: The medical records and ultrasound images of 107 patients with testicular tumor were reviewed. Demographic and clinical characteristics and ultrasound findings of patients with seminoma were compared to those of patients with non-seminoma. RESULTS: 55 patients had seminoma (1 bilateral) and 52 non seminoma. Ultrasound images of seminoma were more often hypoechoic, homogeneous, and lobulated than those of non-seminoma (p < 0.001). Images of non-seminoma were more often heterogeneous and cystic (p < 0.001). There was no difference in tumor size, multiplicity, presence of calcium or lesion margination. Testicular microlithiasis was more common in seminoma (p < 0.02). CONCLUSION: Careful analysis of ultrasound images can permit an educated assessment of testicular tumor histopathology. PMID- 22677785 TI - Nrf2 activation prevents cadmium-induced acute liver injury. AB - Oxidative stress plays an important role in cadmium-induced liver injury. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that up regulates cytoprotective genes in response to oxidative stress. To investigate the role of Nrf2 in cadmium-induced hepatotoxicity, Nrf2-null mice, wild-type mice, kelch-like ECH-associated protein 1-knockdown (Keap1-KD) mice with enhanced Nrf2, and Keap1-hepatocyte knockout (Keap1-HKO) mice with maximum Nrf2 activation were treated with cadmium chloride (3.5mg Cd/kg, i.p.). Blood and liver samples were collected 8h thereafter. Cadmium increased serum alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) activities, and caused extensive hepatic hemorrhage and necrosis in the Nrf2-null mice. In contrast, Nrf2-enhanced mice had lower serum ALT and LDH activities and less morphological alternations in the livers than wild-type mice. H(2)DCFDA (2',7'-dichlorodihydrofluoresein diacetate) staining of primary hepatocytes isolated from the four genotypes of mice indicated that oxidative stress was higher in Nrf2-null cells, and lower in Nrf2 enhanced cells than in wild-type cells. To further investigate the mechanism of the protective effect of Nrf2, mRNA of metallothionein (MT) and other cytoprotective genes were determined. Cadmium markedly induced MT-1 and MT-2 in livers of all four genotypes of mice. In contrast, genes involved in glutathione synthesis and reducing reactive oxygen species, including glutamate-cysteine ligase (Gclc), glutathione peroxidase-2 (Gpx2), and sulfiredoxin-1 (Srxn-1) were only induced in Nrf2-enhanced mice, but not in Nrf2-null mice. In conclusion, the present study shows that Nrf2 activation prevents cadmium-induced oxidative stress and liver injury through induction of genes involved in antioxidant defense rather than genes that scavenge Cd. PMID- 22677787 TI - The natriuretic peptide time-course in end-stage heart failure patients supported by left ventricular assist device implant: focus on NT-proCNP. AB - This study aimed to evaluate left ventricular assist device (LVAD) effects on natriuretic peptide (NP) prohormone plasma levels in end-stage heart failure (HF) patients, especially NT-proCNP, in order to better characterize the NP system during hemodynamic recovery by LVAD. HF patients (n=17, NYHA III-IV) undergoing LVAD were studied: 6 died of multi-organ failure syndrome (NS) and 11 survived (S). Total sequential organ failure assessment (t-SOFA) score and blood samples were obtained at admission (T1) and at 24, 72h and 1, 2, 4 weeks (T2-T6) after LVAD. In S, NT-proANP and NT-proCNP significantly increased at 24h after implantation, reaching a reduction to basal levels at 4 weeks following LVAD [NT proANP: T1 vs. T2 p=0.017, NT-proCNP: T1 vs. T2 p=0.028, T1 vs. T3 p=0.043]. Elevated NT-proBNP plasma levels were observed at all times. In NS, NP plasma levels sustained higher with respect to S. No statistical variation was observed for NT-proCNP and NT-proANP in S and NS while NT-proBNP reached significant differences at T4 in NS. Considering S+NS, only NT-proCNP strongly correlated with t-SOFA score at T1 (rho=0.554, p=0.04) while subdividing patients NT-proCNP positively correlated in NS with t-SOFA score (rho=0.988, p=0.002) only at T4. In NS a correlation between NT-proCNP and NT-proBNP at T1 was observed (rho=-0.900, p=0.037). Both IL-6 and TNF-alpha sustained higher in NS patients than in S; in particular, statistical significance was observed for IL-6. The study of new peptides, such as NT-proCNP, would provide additional information for identifying patients who are more likely to recover. PMID- 22677788 TI - AKAP79 modulation of L-type channels involves disruption of intramolecular interactions in the CaV1.2 subunit. AB - L-type voltage gated calcium channels (VGCCs) interact with a variety of proteins that modulate both their function and localization. A-Kinase Anchoring Proteins (AKAPs) facilitate L-type calcium channel phosphorylation through beta adrenergic stimulation. Our previous work indicated a role of neuronal AKAP79/150 in the membrane targeting of Ca(V)1.2 L-type calcium channels, which involved a proline rich domain (PRD) in the intracellular II-III loop of the channel.(1) Here, we show that mutation of proline 857 to alanine (P857A) into the PRD does not disrupt the AKAP79-induced increase in Ca(v)1.2 membrane expression. Furthermore, deletion of two other PRDs into the carboxy terminal domain of Ca(V)1.2 did not alter the targeting role of AKAP79. In contrast, the distal carboxy terminus region of the channel directly interacts with AKAP79. This protein-protein interaction competes with a direct association of the channel II-III linker on the carboxy terminal tail and modulates membrane targeting of Ca(V)1.2. Thus, our results suggest that the effects of AKAP79 occur through relief of an autoinhibitory mechanism mediated by intramolecular interactions of Ca(v)1.2 intracellular regions. PMID- 22677789 TI - Impact of pancreatic margin status and lymph node metastases on recurrence after resection for invasive and noninvasive intraductal papillary mucinous neoplasms of the pancreas: a meta-analysis. AB - BACKGROUND: Accurate information is currently lacking regarding the values of positive margins (M(+)) and lymph node (LN) metastases as independent predictors of postoperative recurrence in invasive and noninvasive intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. METHODS: A comprehensive online literature search identified all types of primary studies that included M(+) and LN metastases as risk factors and defined recurrence as an outcome in patients with IPMNs. Suitable articles were also identified by manually researching references in qualifying articles. A meta-analysis of the result was performed using a random effects model. RESULTS: The recurrence rate in noninvasive IPMNs was 3.72% in patients with negative margin (M(-)) versus 9.56% in those with M(+) (odds ratio, OR = 0.37, 95% confidence interval, 95% CI: 0.17-0.78, p = 0.010). The recurrence rate in invasive M(-) IPMNs in was 33.85% compared to 53.66% in M(+) IPMNs (OR = 0.47, 95% CI: 0.25-0.88, p = 0.020). The recurrence rate in invasive IPMNs with positive LN was 76.92% compared to 30.86% with negative LN; OR = 0.15, 95% CI: 0.06-0.37, p < 0.0001). CONCLUSIONS: M(+) were associated with disease recurrence in all patients with IPMN, and nodal metastases were significantly associated with recurrence in invasive IPMN. PMID- 22677790 TI - Effect of postnatal intermittent hypoxia on growth and cardiovascular regulation of rat pups. AB - BACKGROUND: Intermittent hypoxic episodes are common among preterm infants, although longer term consequences on growth pattern and cardiovascular regulation are unclear. Furthermore, the effects of intermittent hypoxia (IH) may depend on the pattern of hypoxia-reoxygenation. OBJECTIVES: We tested the hypothesis that a clustered versus dispersed pattern of repetitive IH during early postnatal life would induce differential long-term alteration in growth and cardiovascular regulation. METHODS: Sprague-Dawley rat pups were exposed to room air or to one of two patterns of IH (clustered vs. dispersed) from 1 to 7 days of life. Body weight was measured daily for the first 8 days and weekly from weeks 2 to 8. Blood pressure (BP) and heart rate were measured weekly from weeks 4 to 8 using a noninvasive tail-cuff method for awake, nonanesthetized animals. RESULTS: Exposure to both patterns of repetitive IH induced early growth restriction followed by later catch-up of growth to controls 3 weeks after completion of IH exposures. IH-exposed rats exhibited a sustained decrease in heart rate regardless of the hypoxic exposure paradigm employed. In contrast, a differential response was seen for arterial pressure; the clustered paradigm was associated with a significantly lower BP versus controls, while the pups exposed to the dispersed paradigm showed no effect on BP. CONCLUSION: We speculate that repetitive IH during a critical developmental window and regardless of IH exposure paradigm contributes to prolonged changes in sympathovagal balance of cardiovascular regulation. PMID- 22677791 TI - Overexpression of AtHsfB4 induces specific effects on root development of Arabidopsis. AB - The functions of plant class B-heat shock factors (Hsfs) are not well understood. Hsfs belonging to this group differ from class A-Hsfs in structural features of the oligomerization domain and by the absence of a typical AHA motif for transcriptional activation. AtHsfB4 is expressed in different parts of the plants with highest levels in root tissue. Transgenic Arabidopsis plants overexpressing (OE) HsfB4 by CaMV-35S-promoter showed massively enhanced levels of Hsf mRNAs. The root surface of OE-plants was rough and cells became detached. Crossings with cell type specific root marker lines and confocal laser scanning microscopy provided clear evidence for a duplication of cells in the ground tissue and ectopic layers of lateral root cap (LRC) cells in HsfB4-OE plants. A duplication of endodermis cells occurs already during embryonic development, while the ectopic LRC cells are only detected during postembryonic growth. The mutant phenotypes of Hsf-OE plants are without precedence and indicate that class B-Hsfs may play an important role in root development. PMID- 22677792 TI - Ligand-independent activation of the Hedgehog pathway displays non-cell autonomous proliferation during eye development in Drosophila. AB - Deregulation of the Hedgehog (Hh) signaling pathway is associated with the development of human cancer including medullobastoma and basal cell carcinoma. Loss of Patched or activation of Smoothened in mouse models increases the occurrence of tumors. Likewise, in a Drosophila eye model, deregulated Hedgehog signaling causes overgrowth of eye and head tissues. Surprisingly, we show that cells with deregulated Hh signaling do not or only little contribute to the tissue overgrowth. Instead, they become more sensitive to apoptosis and may eventually be eliminated. Nevertheless, these mutant cells increase proliferation in the adjacent wild-type tissue, i.e., in a non-cell autonomous manner. This non cell autonomous effect is position-dependent and restricted to mutant cells in the anterior portion of the eye. We also observe precocious non-cell autonomous differentiation in genetic mosaics with deregulated Hh signaling. Together, these non-cell autonomous growth and differentiation phenotypes in the Drosophila eye model reveal another strategy by which oncogenes may generate a supportive micro environment for tumor growth. PMID- 22677793 TI - Prediction of cardiovascular events, diabetic nephropathy, and mortality by albumin concentration in a spot urine sample in patients with type 2 diabetes. AB - AIMS: To analyze in a random urine spot the predictive value of urinary albumin concentration (UAC) for cardiovascular events, diabetic nephropathy (DN), and death in patients with type 2 diabetes. METHODS: In this cohort, urinary albumin (immunoturbidimetry) was measured as 24-h urinary albumin excretion (UAE) and, in a random spot urine, as UAC and albumin:creatinine ratio (ACR). Primary outcomes were: 1) cardiovascular events, 2) DN defined as a composite outcome [macroalbuminuria and/or decreased glomerular filtration rate (GFR) <60 ml/min/1.73 m2], and 3) death. RESULTS: A total of 199 type 2 diabetic patients, aged 59.9 +/- 9.9 years, were followed for 6.1 +/- 2.7 years. UAC >=14.4 mg/l, as determined by ROC curve, predicted DN and prediction for this and other outcomes were compared with traditional microalbuminuria cutoffs for ACR and UAE. The outcomes frequency was: cardiovascular events = 26.4%, DN = 31.7% (23.5% decreased GFR; 13.6% macroalbuminuria) and death = 8.50%. In Cox analyses, UAC >=14 mg/l increased the risk (hazard ratio, HR) for cardiovascular events 3.25 times (95% CI 1.43-7.38; P = 0.005), 4.30 for DN composite outcome (95% CI 2.22 8.32; P <0.001), and 5.51 for death (95% CI 1.16-26.22; P = 0.032). Corresponding HRs of ACR >=30 mg/g were: 2.89 (95% CI 1.29-6.45; P = 0.009) for cardiovascular events, 4.67 (95% CI 2.34-9.34; P <0.001) for DN composite outcome and 5.07 (95% CI 1.01-24.88; P = 0.049) for death. HRs of UAE >=30 mg/24-h were: 2.20 (95% CI 2.08-2.49; P = 0.030) for cardiovascular events, 6.76 (95% CI 3.32-13.77; P <0.001) for DN composite outcome, and 2.47 (95% CI 0.72-8.42; P = 0.150) for death. CONCLUSIONS: In conclusion, random UAC >=14 mg/l predicted cardiovascular events, diabetic nephropathy, and mortality just as well as ACR. UAC may be used to assess cardiovascular and renal risks in patients with type 2 diabetes. PMID- 22677794 TI - Pre-diabetes as a contributor to stroke. PMID- 22677795 TI - Effect of pre-diabetes on future risk of stroke: meta-analysis. AB - OBJECTIVES: To assess the association between pre-diabetes and risk of stroke, and to evaluate whether this relation varies by diagnostic criteria for pre diabetes. DESIGN: Systematic review and meta-analysis of prospective studies. DATA SOURCES: A search of Medline, Embase, and the Cochrane Library (1947 to 16 July 2011) was supplemented by manual searches of bibliographies of key retrieved articles and relevant reviews. SELECTION CRITERIA: Prospective cohort studies that reported multivariate adjusted relative risks and corresponding 95% confidence intervals for stroke with respect to baseline pre-diabetes were included. DATA EXTRACTION: Two independent reviewers extracted data on pre diabetes status at baseline, risk estimates of stroke, study quality, and methods used to assess pre-diabetes and stroke. Relative risks were pooled using random effects models when appropriate. Associations were tested in subgroups representing different characteristics of participants and studies. Publication bias was evaluated with funnel plots. RESULTS: The search yielded 15 prospective cohort studies including 760,925 participants. In 8 studies analysing pre diabetes defined as fasting glucose 100-125 mg/dL (5.6-6.9 mmol/L), the random effects summary estimate did not show an increased risk of stroke after adjustment for established cardiovascular risk factors (1.08, 95% confidence interval 0.94 to 1.23; P = 0.26). In 5 studies analysing pre-diabetes defined as fasting glucose 110-125 mg/dL (6.1-6.9 mmol/L), the random effects summary estimate showed an increased risk of stroke after adjustment for established cardiovascular risk factors (1.21, 1.02 to 1.44; P = 0.03). In 8 studies with information about impaired glucose tolerance or combined impaired glucose tolerance and impaired fasting glucose, the random effects summary estimate showed an increased risk of stroke after adjustment for established cardiovascular risk factors (1.26, 1.10 to 1.43; P < 0.001). When studies that might have enrolled patients with undiagnosed diabetes were excluded, only impaired glucose tolerance or a combination of impaired fasting glucose and impaired glucose tolerance independently raised the future risk of stroke (1.20, 1.07 to 1.35; P = 0.002). CONCLUSION: Pre-diabetes, defined as impaired glucose tolerance or a combination of impaired fasting glucose and impaired glucose tolerance, may be associated with a higher future risk of stroke, but the relative risks are modest and may reflect underlying confounding. PMID- 22677796 TI - Should we abandon cervical spine manipulation for mechanical neck pain? Yes. PMID- 22677797 TI - Should we abandon cervical spine manipulation for mechanical neck pain? No. PMID- 22677798 TI - Glyphosate in northern ecosystems. AB - Glyphosate is the main nonselective, systemic herbicide used against a wide range of weeds. Its worldwide use has expanded because of extensive use of certain agricultural practices such as no-till cropping, and widespread application of glyphosate-resistant genetically modified crops. Glyphosate has a reputation of being nontoxic to animals and rapidly inactivated in soils. However, recent evidence has cast doubts on its safety. Glyphosate may be retained and transported in soils, and there may be cascading effects on nontarget organisms. These processes may be especially detrimental in northern ecosystems because they are characterized by long biologically inactive winters and short growing seasons. In this opinion article, we discuss the potential ecological, environmental and agricultural risks of intensive glyphosate use in boreal regions. PMID- 22677799 TI - Quantifying increased hepatic arterial flow with test balloon occlusion of the splenic artery in liver transplant recipients with suspected splenic steal syndrome: quantitative digitally subtracted angiography correlation with arterial Doppler parameters. AB - PURPOSE: The purpose of this study is to quantify hepatic arterial flow (HAF) in liver transplants with splenic steal syndrome (SSS) pre- and post-test balloon occlusion of the splenic artery utilizing Doppler ultrasound (DUS) and quantitative digitally subtracted angiography (Q-DSA). METHODS: A total of 193 liver transplants were evaluated retrospectively. Hepatic arterial velocity (HAV) and HAF were calculated utilizing DUS and Q-DSA (i-flow prototype, Siemens) pre- and post-splenic artery balloon occlusion. The rate of HAF increase, total HAF, and peak contrast density (PKD) by Q-DSA were compared with HAF by DUS. RESULTS: Of all, 4 suspected SSS cases underwent test-balloon occlusion with DUS and Q DSA. Using DUS, HAV and HAF increased by 1.6- to 1.8-fold and 1.7- to 2.6-fold, respectively. Using Q-DSA, the HAF rate, total HAF, and PKD increased by 1.1 to 12.8, 1.5 to 7.6, and 1.3 to 5.3, respectively. CONCLUSION: Occlusion of the splenic artery in liver transplants with SSS doubles the HAF (+1.7- to 2.6-fold). The Q-DSA parameters correlate qualitatively but overestimate the resultant increased HAF. PMID- 22677800 TI - First principles molecular dynamics study of nitrogen vacancy complexes in boronitrene. AB - We present the results of first principles molecular dynamics simulations of nitrogen vacancy complexes in monolayer hexagonal boron nitride. The threshold for local structure reconstruction is found to be sensitive to the presence of a substitutional carbon impurity. We show that activated nitrogen dynamics triggers the annihilation of defects in the layer through formation of Stone-Wales-type structures. The lowest energy state of nitrogen vacancy complexes is negatively charged and spin polarized. Using the divacancy complex, we show that their formation induces spontaneous magnetic moments, which is tunable by electron or hole injection. The Fermi level s-resonant defect state is identified as a unique signature of the ground state of the divacancy complex. Due to their ability to enhance structural cohesion, only the divacancy and the nitrogen vacancy carbon antisite complexes are able to suppress the Fermi level resonant defect state to open a gap between the conduction and valence bands. PMID- 22677801 TI - The prevalence of hypertension, valve calcification and left ventricular hypertrophy and geometry in peritoneal dialysis patients. AB - BACKGROUND/AIMS: Cardiac valve calcification (CVC) and left ventricular (LV) abnormalities are common indicators of a poor prognosis in dialysis patients. We determined the prevalence of hypertension, CVC, LV hypertrophy (LVH) and LV geometry in peritoneal dialysis (PD) patients. METHODS: Eighty-seven patients (50 female; mean age 42 +/- 13 years; mean dialysis duration 46 +/- 24 months) on strict salt and volume restriction, none of whom were receiving antihypertensives, were included in the study. Blood pressure (BP), biochemical parameters, CVC, LVH and LV geometry were determined. RESULTS: Most patients were normotensive. CVC of the mitral and aortic valves and of both valves were noted in 22, 23 and 15% of patients, respectively. Patients with CVC had significantly higher diastolic BP (p = 0.023), cardiothoracic index (CTI; p = 0.037) and LV mass index (LVMI; p = 0.002). LVH, noted overall in 44% of cases, was present in 62 and 36% of the patients with and without CVC, respectively (p = 0.028). Of the whole group, only 50.6% had normal LV geometry. LVH was associated with lower serum albumin (p = 0.002), higher CTI (p = 0.027) and more frequent CVC (p = 0.028). LVMI was greater in patients with CVC (p = 0.002). CONCLUSION: Strict salt restriction and the achievement of ideal dry weight result in normotension in PD patients. CVC is associated with LVH, both of which are lower in normotensive patients. PMID- 22677802 TI - YF3:Ln3+ (Ln = Ce, Tb, Pr) submicrospindles: hydrothermal synthesis and luminescence properties. AB - YF(3):Ln(3+) (Ln = Ce, Tb, Pr) microspindles were successfully fabricated by a facile hydrothermal method. X-Ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM), lifetimes, photoluminescence (PL) and low-voltage cathodoluminescence (CL) were used to characterize the resulting samples. The lengths and diameters of YF(3):0.02Ce(3+) microspindles are around 760 nm and 230 nm, respectively. Adding dilute acid and trisodium citrate (Cit(3-)) are essential for obtaining YF(3) microspindles. A potential formation mechanism for YF(3) microspindles has been presented. PL spectroscopy investigations show that YF(3):Ce(3+) and YF(3):Tb(3+) microcrystals exhibit the characteristic emission of Ce(3+) 5d -> 4f and Tb(3+ 5)D(4)->(7)F(J) (J = 6-3) transitions, respectively. In addition, the energy transfer from Ce(3+) to Tb(3+) was investigated in detail for YF(3):Ce(3+), Tb(3+) microspindles. Under the excitation of electron beams, YF(3):Pr(3+) show quantum cutting emission and YF(3):Ce(3+), Tb(3+) phosphors exhibit more intense green emission than the commercial phosphor ZnO:Zn. PMID- 22677803 TI - Improved method for the isolation, characterization and examination of neuromuscular and toxic properties of selected polypeptide fractions from the crude venom of the Taiwan cobra Naja naja atra. AB - An improved chromatographic method was developed to isolate and purify polypeptides and proteins from the crude venom of the Taiwan cobra Naja naja atra. The procedure devised is simple, easy to reproduce, and enables large scale isolation of almost all polypeptides and proteins in this cobra venom. Six pure polypeptide fractions of the venom were isolated and characterized using gel filtration on Sephadex G50 (medium), ion exchange chromatography on SP-Sephadex C25, desalting on Sephadex G25 (fine) and preparative HPLC on a RPC 18 column. The neuromuscular activity of these fractions was tested on the chick biventer cervicis nerve-muscle preparation and their toxicity (LD(50)) was determined after i.v. administration in mice. Their antinociceptive activity was tested in the mouse abdominal test by i.v. application. Two of these polypeptide samples had major physiological effects: one acted as a cardiotoxin causing reversible myocardial contractures with no effect on muscle twitches elicited by nerve stimulation (NS); another was a neurotoxin that blocked muscle contractions in response to NS and exogenously added acetylcholine. The cardiotoxic fraction was identified as CTX I, a well-known cardiotoxin present in this venom, and the neurotoxin was identified as neurotoxin-alpha with an LD50 in mice of 0.075 mg/kg. PMID- 22677804 TI - Recombinant expression of mutants of the Frankenstein disintegrin, RTS ocellatusin. Evidence for the independent origin of RGD and KTS/RTS disintegrins. AB - The requirements to transform a short disintegrin of the RGD clade into an RTS disintegrin, were investigated through the generation of recombinant mutants of ocellatusin in which the RGD tripeptide was substituted for RTS in different positions along the integrin-specificity loop. Any attempt to create an active integrin alpha(1)beta(1) inhibitory motif within the specificity loop of ocellatusin was unsuccessful. Replacing the whole RGD-loop of ocellatusin by the RTS-loop of jerdostatin was neither sufficient for confering alpha(1)beta(1) binding specificity to this ocellatusin-RTS Frankenstein(2) mutant. Factors other than the integrin-binding loop sequence per se are thus required to transform a disintegrin scaffold from the RGD clade into another scaffold from the RTS/KTS clade. Moreover, our results provide evidences, that the RTS/KTS short disintegrins have potentially been recruited into the venom gland of Eurasian vipers independently from the canonical neofunctionalization pathway of the RGD disintegrins. PCR-amplifications of jerdostatin-like sequences from a number of taxa across reptiles, including snakes (Crotalinae, Viperinae, and Elapidae taxa) and lizards (Lacertidae and Iguanidae) clearly showed that genes coding for RTS/KTS disintegrins existed long before the split of Lacertidae and Iguania, thus predating the recruitment of the SVMP precursors of disintegrins, providing strong support for the view of an independent evolutionary history of the RTS/KTS and the RGD clades of short disintegrins. PMID- 22677805 TI - Identification of linear B-cell epitopes on myotoxin II, a Lys49 phospholipase A2 homologue from Bothrops asper snake venom. AB - Knowledge on toxin immunogenicity at the molecular level can provide valuable information for the improvement of antivenoms, as well as for understanding toxin structure-function relationships. The aims of this study are two-fold: first, to identify the linear B-cell epitopes of myotoxin II from Bothrops asper snake venom, a Lys49 phospholipase A2 homologue; and second, to use antibodies specifically directed against an epitope having functional relevance in its toxicity, to probe the dimeric assembly mode of this protein in solution. Linear B-cell epitopes were identified using a library of overlapping synthetic peptides spanning its complete sequence. Epitopes recognized by a rabbit antiserum to purified myotoxin II, and by three batches of a polyvalent (Crotalidae) therapeutic antivenom (prepared in horses immunized with a mixture of B. asper, Crotalus simus, and Lachesis stenophrys venoms) were mapped using an enzyme immunoassay based on the capture of biotinylated peptides by immobilized streptavidin. Some of the epitopes identified were shared between the two species, whereas others were unique. Differences in epitope recognition were observed not only between the two species, but also within the three batches of equine antivenom. Epitope V, located at the C-terminal region of this protein, is known to be relevant for toxicity and neutralization. Affinity-purified rabbit antibodies specific for this site were able to immunoprecipitate myotoxin II, suggesting that the two copies of epitope V are simultaneously available to antibody binding, which would be compatible with the mode of dimerization known as "conventional" dimer. PMID- 22677806 TI - Mipartoxin-I, a novel three-finger toxin, is the major neurotoxic component in the venom of the redtail coral snake Micrurus mipartitus (Elapidae). AB - The major venom component of Micrurus mipartitus, a coral snake distributed from Nicaragua to northern South America, was characterized biochemically and functionally. This protein, named mipartoxin-I, is a novel member of the three finger toxin superfamily, presenting the characteristic cysteine signature and amino acid sequence length of the short-chain, type-I, alpha-neurotoxins. Nevertheless, it varies considerably from related toxins, with a sequence identity not higher than 70% in a multiple alignment of 67 proteins within this family. Its observed molecular mass (7030.0) matches the value predicted by its amino acid sequence, indicating lack of post-translational modifications. Mipartoxin-I showed a potent lethal effect in mice (intraperitoneal median lethal dose: 0.06 MUg/g body weight), and caused a clear neuromuscular blockade on both avian and mouse nerve-muscle preparations, presenting a post-synaptic action through the cholinergic nicotinic receptor. Since mipartoxin-I is the most abundant (28%) protein in M. mipartitus venom, it should play a major role in its toxicity, and therefore represents an important target for developing a therapeutic antivenom, which is very scarce or even unavailable in the regions where this snake inhabits. The structural information here provided might help in the preparation of a synthetic or recombinant immunogen to overcome the limited venom availability. PMID- 22677807 TI - Protection by Mikania laevigata (guaco) extract against the toxicity of Philodryas olfersii snake venom. AB - Philodryas olfersii is responsible for most colubrid snakebites in Brazil. In this work, we examined the ability of an ethanolic extract from Mikania laevigata (guaco) leaves to protect against the in vitro neuromuscular activity of P. olfersii venom in mouse phrenic nerve-diaphragm (PND) and chick biventer cervicis (BC) preparations. M. laevigata extract caused moderate twitch-tension facilitation at low concentrations (107.4 +/- 6.2% with 20 MUl/ml and 118.9 +/- 9.3% with 40 MUl/ml in PND, and 120.7 +/- 7.7% with 40 MUl/ml and 114.5 +/- 4.4% with 50 MUl/ml in BC after 120 min; n = 4-6, mean +/- SEM). In PND, the ethanol alone (40 MUl/ml, n = 4) did not change the twitch-tension when compared with control. However, in BC, the ethanol produced a higher facilitation when compared to control. At higher concentrations (>50 MUl/ml) the extract caused total and reversible blockade in both preparations. Venom (50 MUg/ml) caused partial blockade in PND (58.5 +/- 12%, n = 4) and almost total blockade in BC (93.5 +/- 2.2%, n = 4). Pretreatment of the preparations with extract (40 MUl/ml) for 30 min before incubation with venom (50 MUg/ml) completely protected PND from neuromuscular blockade and delayed the blockade in BC. The extract alone caused only mild morphological alterations (12.5 +/- 0.5% and 10.9 +/- 2.3% fiber damage in PND and BC, respectively, compared to 2.3 +/- 0.3% and 3 +/- 0 in controls; n = 3), with no increase in expression of the inflammatory cytokines TNFalpha and IFNgamma. The ethanol alone also caused slight muscle damage: 4.3 +/- 2.4% in PND and 6.7 +/- 3.3% in BC (both n = 3) and little or no TNFalpha and IFNgamma expression in both preparations as observed in control. Venom (50 MUg/ml) caused 53.5 +/- 8.5% and 55.8 +/- 4.3% fiber damage in PND and BC, respectively; (n = 3, p < 0.05 vs. controls) and enhanced expression of TNFalpha and IFNgamma. Pretreatment of the preparations with extract protected against venom-induced muscle damage by 80.3 and 60.4 in PND and BC, respectively, and prevented TNFalpha and IFNgamma expression. These results indicate that the M. laevigata extract protected nerve-muscle preparations against the myotoxic, neurotoxic and inflammatory effects of P. olfersii venom. PMID- 22677808 TI - Sticholysin II: a pore-forming toxin as a probe to recognize sphingomyelin in artificial and cellular membranes. AB - Sphingomyelin is a major component of membrane rafts, and also is a precursor of many bioactive molecules. The sphingomyelin plays important biological roles and alterations of its metabolism are the basis of some genetic disorders such as the Niemann Pick disease. A complete understanding of its biological role is frustrated by the lack of efficient tools for its recognition in the cell. Sticholysin II (StnII) is a 20 kDa protein from the sea-anemone Stichodactyla helianthus which shows a cytotoxic activity by forming oligomeric aqueous pores in the cell plasma membrane. A recent NMR analysis indicates that the sticholysin II binds specifically to sphingomyelin by two domains that recognize respectively the hydrophilic (i.e. phosphorylcholine) and the hydrophobic (i.e. ceramide) moieties of the molecule. Aim of our research has been to verify the possible employ of an antibody against the StnII to investigate the localization and the dynamics of sphingomyelin in cell membranes. For this purpose, we developed a monoclonal antibody (named A10) against the toxin and we tested its ability to bind StnII after binding to sphingomyelin. A10 antibody is able to recognize the sticholysin II both in its native form and after SDS treatment, being the protein still suitable for many analytic techniques such as ELISA, western blotting and immunofluorescence. The high affinity of the toxin for the sphingomyelin in cell membranes has been demonstrated by microscopic immuno-localization and western blot analysis; both methods confirmed that sphingomyelin is the molecular acceptor for StnII also in cell membranes. Finally, we studied the specificity of the toxin for sphingomyelin by a cell membrane-double labelling method, using cholera toxin, specific for the ganglioside GM1, and sticholysin II. The results obtained show that there is no cross-reactivity between the two toxins, confirming that sticholysin II is able to discriminate among membrane domains with sphingomyelin with respect to those enriched with gangliosides. PMID- 22677809 TI - High glycated hemoglobin levels and intracranial artery stenosis are predictive factors for early motor worsening events in patients with penetrating artery infarction. AB - BACKGROUND: The purpose of this study was to identify typical clinical characteristics to predict early motor worsening (EMW) of patients with penetrating artery infarction. METHODS: We reviewed 65 consecutive patients with pure motor hemiparesis, sensorimotor stroke, and ataxic hemiparesis. EMW was defined as deterioration by >=1 point on the National Institutes of Health Stroke Scale for motor function within 5 days of admission. RESULTS: EMW was observed in 22 patients (34%). HbA1c levels were higher in patients with EMW than in those without EMW (7.9 +/- 2.6 vs. 6.3 +/- 1.6%; p < 0.01). The percentage of EMW patients with intracranial artery stenosis (ICAS) was greater than that of non EMW patients with ICAS (13/22 patients, 59% vs. 8/43 patients, 19%; p < 0.01). Multivariate logistic regression analysis indicated that HbA1c levels >=7.0% (OR 3.0, 95% CI 1.5-6.8; p < 0.005) or ICAS (OR 2.3, 95% CI 1.2-4.8; p < 0.05) increased the risk of EMW, and the combination of these factors increased the risk in an additive manner (OR 7.6, 95% CI 2.5-40; p < 0.005). CONCLUSION: HbA1c levels >=7.0% and/or ICAS in patients with penetrating artery infarction are associated with EMW. PMID- 22677810 TI - Identification of a histaminergic circuit in the caudal hypothalamus: an evidence for functional heterogeneity of histaminergic neurons. AB - It is well established that histaminergic neurons in the posterior hypothalamus make connections with whole brain areas and regulate several functions. Recent evidence indicates that histaminergic neurons are heterogeneous cell group and organized into distinct circuits. However, functional circuits of histaminergic neurons have not been fully mapped so far. To address this issue, we have investigated antihistamine-sensitive neuronal activation in the hypothalamus to determine the hypothalamic region primarily innervated by histaminergic neurons. Here we review our recent findings showing the existence of the heterogeneous subpopulations of histaminergic neurons in the TMN that innervated distinct regions to regulate particular functions. We have identified the caudal part of the arcuate nucleus of hypothalamus (cARC) as a target region of histaminergic neurons in food-restricted rats by assessing suppression of c-Fos expression by pretreatment with antihistamines. Histaminergic neurons in the tuberomammillary nucleus (TMN) are morphologically subdivided into five groups (E1-E5). Among the subdivisions, the E3 group was found to be activated corresponding to the activation of cARC neurons. Our findings suggest that this subpopulation selectively innervate cARC neurons. Accumulating reports have also described c Fos expression in other TMN subpopulations. Various stress challenge induced c Fos expression primarily in E4 and E5 subpopulations. Motivation- and drug induced arousal elicited in common activation of ventrolateral part of the TMN containing E1 and E2 subdivisions, which receive projections from wake-active orexin neurons and sleep-active GABA neurons. These lines of evidence support the hypothesis that there are heterogeneous subpopulations in the TMN that innervated distinct regions to regulate particular functions. PMID- 22677811 TI - Effects of midazolam and nitrous oxide on endocrine and metabolic measurements in children. AB - OBJECTIVE: Pain, stress as well as drugs may affect metabolic and endocrine measurements, especially in stressed children. The aim was to study how release of glucose and stress hormones are affected when procedural sedation with nitrous oxide or midazolam are used for establishing intravenous access in obese and lean children. METHODS: In a prospective, double-blind, randomized study 90 children, 60 obese and 30 growth-retarded (GR), aged 5-18 years, with reported anxiety or difficulties connected with i.v. access, were randomized to 1 of 3 groups: oral midazolam (0.3 mg/kg, max. 15 mg), 50% nitrous oxide (N(2)O), and 10% N(2)O. In addition, all children received anesthesia cream (EMLA(r)) locally 1 h before i.v. access. Blood samples were drawn at 4 time points during 30 min after establishing venous access and, when feasible, after 24 h. The 24-hour sample was regarded as obtained during unstressed condition. The effect of procedural sedation was analyzed. Children's evaluations of pain (Numeric Rating Scale) and procedure (Likert Scale) were correlated with mean values of cortisol and glucose after i.v. access. For the metabolic and hormone control measurements, 60 children aged 4-18 years (40 obese and 20 GR) served as controls. These children underwent a 24-hour blood sampling and did not receive sedation. The control samples were drawn 10-12 h after i.v. access. RESULTS: After midazolam, significantly lower cortisol levels were found compared to both 50% N(2)O and 10% N(2)O and to unstressed controls. The growth hormone levels decreased with time in the midazolam group compared to 50 and 10% N(2)O, where the effect of time was reversed. Glucose levels among GR children increased from 0 to 30 min, whereas the opposite was found in obese children regardless of treatment. A post hoc analysis demonstrated significant correlations between children's evaluations of the procedure and mean values of cortisol (r = -0.53), growth hormone (r = 0.52), and norepinephrine (r = -0.5) in children treated with a very low dose of N(2)O (10%). CONCLUSIONS: When sedation is insufficient during i.v. access, and blood sampling pain and stress affect hormone values, treatment with N(2)O or midazolam influence the glucose and stress hormone levels differently. These differences need to be accounted for when results are used for diagnosis and clinical decisions. PMID- 22677812 TI - Cardioprotection with 8-O-acetyl shanzhiside methylester on experimental myocardial ischemia injury. AB - 8-O-acetyl shanzhiside methylester (ND01) was isolated from the leaves of Lamiophlomis rotata (Benth.) Kudo. In this study, we investigated the anti myocardial ischemia and reperfusion (I/R) injury effects of ND01 in vivo and elucidated the potential mechanism in vitro. The results indicated that ND01 significantly attenuated hypoxia-induced cytotoxicity in a concentration dependent manner in H9c2 cells. Treatment of H9c2 cells with ND01 9 MUM blocked TNF-alpha-induced nuclear factor kappaB (NF-kappaB) phosphorylation by blocking High-mobility group box1 (HMGB1) expression. Treatment of rats with ND01 10mg/kg, (i.v.) protected the animals from myocardial I/R injury as indicated by a decrease in infarct volume, improvement in hemodynamics and reduction of myocardial damage severity. Treatment with ND01 also lowered serum levels of pro inflammatory factors and reduced High mobility group box-1 protein (HMGB1) and phosphorylated NF-kappaB expression in ischemic myocardial tissue. Additionally, continuous i.v. of ND01 14 days attenuated cardiac remodeling. These protective effects suggested that ND01 might be due to block of myocardial inflammatory cascades through an HMGB1-dependent NF-kappaB signaling pathway. PMID- 22677813 TI - Comparison of toxicokinetic and tissue distribution of triptolide-loaded solid lipid nanoparticles vs free triptolide in rats. AB - The traditional Chinese medicine Tripterygium wilfordii Hook F (TWHF) is used clinically to treat some autoimmune and inflammatory disorders including rheumatoid arthritis, systemic lupus erythematosus, and skin diseases. However TWHF has a high potential for toxicity, so its clinical use is limited. Solid lipid nanoparticle (SLN) delivery systems are reported to have remarkable advantages over conventional formulations of bioactive plant extracts, such as enhancing solubility and bioavailability, offering protection from toxicity, and enhancing pharmacological activity. We reported previously that a tripterygium glycoside (TG) solid lipid nanoparticle (TG-SLN) delivery system had a protective effect against TG-induced male reproductive toxicity. To better understand this issue, we used triptolide (TP) as a model drug in a comparative study of the toxicokinetic and tissue distribution of TP-SLN and free TP in rats, allowing us to observing the in vivo behavior of this nanoformulation and to assess mechanisms of SLN-related toxicity. A fast and sensitive HPLC-APCI-MS/MS method was developed for the determination of triptolide in rat plasma. Fourteen rats were divided randomly into two groups of 7 rats each for toxicokinetic analysis, with one group receiving free TP (450MUg/kg) and the other receiving the TP-SLN formulation (450MUg/kg). Blood was obtained before dosing and 0.083, 0.17, 0.25, 0.33, 0.5, 0.75, 1, 1.5, 2, 3 and 4h after drug administration. Thirty-six rats were divided randomly into six equal groups for a tissue-distribution study. Half of the rats received intragastric administration of TP (450MUg/kg) and the other half received TP-SLN (450MUg/kg). At 15, 45, and 90min after dosing, samples of blood, liver, kidney, spleen, lung, and testicular tissue were taken. TP concentration in the samples was determined by LC-APCI-MS-MS. The toxicokinetic results for the nanoformulation showed a significant increase the area under the curve (AUC) (P<0.05), significantly longer T(max) and mean retention times (MRTs) (0-t) (P<0.05), significantly decreased C(max) (P<0.05). The nanoformulation promoted absorption with a slow release character, indicating that toxicokinetic changes may be the most important mechanism for the enhanced efficacy of nanoformulations. Tissue-distribution results suggest a tendency for TP concentrations in the lung and spleen to increase, while TP concentrations in plasma, liver, kidney, and testes tended to decrease in the TP-SLN group. At multiple time points, testicular tissue TP concentrations were lower in the TP SLN group than in free TP group. This provides an important clue for the decreased reproductive toxicity observed with TP-SLN. PMID- 22677814 TI - Timbre and speech perception in bimodal and bilateral cochlear-implant listeners. AB - OBJECTIVES: This study was designed to evaluate the contribution of temporal and spectral cues for timbre perception in listeners with a cochlear implant (CI) in one ear and low-frequency residual hearing in the contralateral ear (bimodal hearing), and listeners with two CIs. Specifically, it examined the relationship between timbre and speech perception in these two groups of listeners. It was hypothesized that, similar to speech recognition, temporal-envelope cues are dominant cues for timbre perception, and the reliance of spectral cues was reduced in both bimodal and bilateral CI users compared with that in normal hearing listeners. It was further hypothesized that the patterns of results with regard to combined benefit would be similar between timbre and speech perception. DESIGN: Seven bimodal and five bilateral CI users participated. Sixteen stimuli that synthesized western musical instruments were used for the timbre-perception task. Sixteen consonants in the /aCa/ context and nine monophthongs in the /hVd/ context were used for the phoneme-recognition task. Each subject was tested on three listening conditions-individual device alone (single CI, or hearing aid [HA] alone) and combined use of devices (CI + HA, or 2CIs). For the timbre perception task, each listener made judgments of dissimilarity between stimulus pairs. Multidimensional scaling analysis was performed to derive the coordinates of the dimensions that best fit the data. Correlational analyses were performed to relate the coordinates of each dimension and the temporal-envelope (impulsiveness) and spectral-envelope (spectral-centroid) features of the stimuli. For phoneme-recognition task, each listener identified the phoneme he or she heard by choosing an answer displayed on the computer screen. Overall percent correct phoneme-identification scores and percent information transmission for consonant and vowel features were calculated. RESULTS: There were strong correlations between impulsiveness and the first dimension (Dim 1) of the timbre space, but correlations between spectral centroid and the second dimension (Dim 2) were weak for all listening conditions for both groups of listeners. As a group, the combined use of devices did not significantly improve listeners' ability to perceive differences in musical timbre compared with the better single device condition. Some of the bimodal and bilateral CI users showed a considerably strengthened correlation between spectral centroid and Dim 2 in the combined condition compared with a single CI or an HA. There was a lack of relationship between percent correct phoneme recognition and timbre perception for all listening conditions. However, there was a consistent pattern regarding the combined benefit between timbre perception and vowel recognition. In general, listeners who demonstrated combined benefit for vowel recognition also showed a considerable increase in correlation between spectral centroid and Dim 2 with the combined use of devices compared with the single-device conditions. Improved correlation was not evident for those who did not demonstrate combined benefit for vowel recognition. CONCLUSIONS: Similar to speech recognition, temporal envelope was a dominant cue for timbre perception in bimodal and bilateral CI users. In addition, there was a close relationship between timbre perception and vowel recognition with regard to combined benefit. The present findings suggest that speech recognition and timbre perception could be enhanced when listeners received different spectral cues from individual devices. PMID- 22677815 TI - The influence of audiovisual ceiling performance on the relationship between reverberation and directional benefit: perception and prediction. AB - OBJECTIVES: Acoustically, directional microphone hearing aids are less able to improve signal-to-noise ratio in more-reverberant environments. However, because auditory-visual (AV) omnidirectional performance is more likely to approach the ceiling level in less-reverberant environments, listeners may perceive a smaller directional benefit in these environments. The first objective of this study was to investigate the influence of AV ceiling performance on the relationship between reverberation and directional benefit. The second objective was to determine whether a modified speech intelligibility index (mSII) model could predict directional benefit across AV listening conditions with different levels of reverberation. DESIGN: Nineteen adults with sensorineural hearing loss were recruited. Directional benefit was measured using the auditory-only (AO) Hearing in Noise Test (HINT) and the AV version of the Connected Speech Test (CST) in environments containing either low or moderate levels of reverberation (reverberation time = 0.2 sec and 0.7 sec, respectively). The AO mSII was calculated for both speech materials. To predict AV directional benefit, the AO mSII was converted to the AV mSII using the correction equations specified by American National Standards Institute S3.5-1997 (R2007) and the new equations developed based on the data collected in a low-reverberation sound booth in a previous study. RESULTS: As the test environment became more reverberant, a decrease in directional benefit was measured using the HINT. In contrast, the results of the AV CST revealed that directional benefit was higher in the more reverberant condition. Although the mSII model accurately predicted the HINT measured directional benefit, the model using the American National Standards Institute correction equations underestimated the directional benefit measured using the AV CST in both reverberation conditions. Applying the newer equations, the model resulted in a more accurate prediction in the low-reverberation condition. However, AV directional benefit in the moderately reverberant condition was still underestimated. CONCLUSIONS: Hearing aid users would achieve the greatest directional benefit in situations in which they do not reach ceiling performance. The present study suggests that in the real world these situations may include face-to-face communication occurring in environments with higher reverberation. The opposite trends demonstrated by the HINT and AV CST highlight the importance of using ecologically valid laboratory testing to estimate the real-world effectiveness of a hearing aid and its technology. As a likely result of the difference in the effect on speech cues between noise and reverberation, the new equations developed from the low-reverberation booth failed to predict AV directional benefit in the more-reverberant environment. The mSII model with visual cue correction equations would be able to provide accurate predictions for AV directional benefit when the acoustic environments are similar to the ones used to derive the equations. PMID- 22677817 TI - Position-orientation adaptive smoothing of diffusion weighted magnetic resonance data (POAS). AB - We introduce an algorithm for diffusion weighted magnetic resonance imaging data enhancement based on structural adaptive smoothing in both voxel space and diffusion-gradient space. The method, called POAS, does not refer to a specific model for the data, like the diffusion tensor or higher order models. It works by embedding the measurement space into a space with defined metric, in this case the Lie group of three-dimensional Euclidean motion SE(3). Subsequently, pairwise comparisons of the values of the diffusion weighted signal are used for adaptation. POAS preserves the edges of the observed fine and anisotropic structures. It is designed to reduce noise directly in the diffusion weighted images and consequently also to reduce bias and variability of quantities derived from the data for specific models. We evaluate the algorithm on simulated and experimental data and demonstrate that it can be used to reduce the number of applied diffusion gradients and hence acquisition time while achieving a similar quality of data, or to improve the quality of data acquired in a clinically feasible scan time setting. PMID- 22677818 TI - Lattice relaxation of graphene under high magnetic field. AB - We investigate the n = 0 Landau level (LL) in monolayer graphene with high magnetic field. We find that the energy gap is opened in the n = 0 LL by the magnetic-field-dependent lattice relaxation originating from the interactions between the electrons (holes) and longitudinal-deformation-acoustic phonon. Both the linear and square-foot dependence of the energy gap on the magnetic field are obtained depending on the choice of the Debye cut-off wave number for the acoustic phonon. The relations of the Huang-Rhys parameter (lattice relaxation strength) and the transition linewidths with the magnetic field are also discussed. Our results agree with the current experiments on graphene in high magnetic field, and provide an alternative explanation for the experimental measurements. PMID- 22677820 TI - Composite and wire bridges. PMID- 22677821 TI - Tongue hook. PMID- 22677822 TI - Direct referral. PMID- 22677823 TI - Bisphosphonate considerations. PMID- 22677824 TI - Cutlery control. PMID- 22677825 TI - Endodontic counterpoint. PMID- 22677827 TI - First time events. PMID- 22677828 TI - Devaluing the kudos. PMID- 22677839 TI - Genetics versus environment in the aetiology of malocclusion. AB - The ongoing debate regarding the relative contributions of heredity and environment to the aetiology of malocclusion would benefit from both a more careful interpretation of the evidence and the abandonment of the tendency to conflate under one umbrella term distinct clinical entities, which may in turn have different aetiologies. D. Normando's letter of 24 February 2012 ( 2012; 212: 153) raises some interesting and surprising points, which deserve attention and comment. PMID- 22677840 TI - Late diagnosis of an occult tumour - what lessons can we learn? AB - OBJECTIVE: Malignant tumours of the nasal cavity and paranasal sinuses are rare and late presentation of a maxillary sinus tumour is common due to the vague nature of the symptoms which can delay diagnosis. METHODS: We report a female with a maxillary sinus tumour who was initially diagnosed with chronic idiopathic facial pain (CIFP) and sinusitis, which subsequently led to a delay in diagnosis and treatment of her tumour. RESULTS: There was no clinical extra- or intra-oral pathology, however, she had varying clinical presentations of facial pain, anosmia, loss of gustatory function, and infra-orbital nerve paraesthesia. CT and MRI scans confirmed obliteration of the left maxillary sinus by a solid mass involving ethmoid and sphenoid sinuses and some cranial nerves. Biopsy confirmed a poorly differentiated carcinoma of the ethmoid and sphenoid sinuses and invasion of the cavernous sinus. CONCLUSION: A morbid, but hidden tumour was left undiagnosed due to the unusual presentation of the patient's symptoms. It is essential that all patients are managed holistically and thorough historical, clinical and radiographic examination and appropriate investigations are carried out to prevent unnecessary and potentially time-wasting treatment. PMID- 22677846 TI - Summary of: Post-implant neuropathy of the trigeminal nerve. A case series. PMID- 22677841 TI - The interdisciplinary management of patients with amelogenesis imperfecta - restorative dentistry. AB - This paper considers the role of the restorative dentist in the interdisciplinary management of patients with amelogenesis imperfecta. General restorative considerations as well as the techniques available are reviewed. Two clinical cases are described to illustrate this. PMID- 22677847 TI - Summary of: What factors influence the provision of preventive care by general dental practitioners? PMID- 22677848 TI - The art of suggestion: the use of hypnosis in dentistry. AB - Hypnodontics, or the use of hypnosis in dentistry, is not widely used throughout the dental profession. Many patients seeking to use this therapy to help them access dental treatment are forced to seek treatment from non-clinically trained hypnotherapists. This article aims to explore what hypnosis is, its applications in dentistry and provide a brief insight into how these hypnotic concepts may be put to use in day-to-day dental practice. PMID- 22677849 TI - Using service rationalisation to build a research network: lessons from the centralisation of UK services for children with cleft lip and palate. AB - In the UK around a thousand children are born annually with a cleft lip and/or palate that requires treatment. In the last decade services have been centralised in the UK reducing the 57 centres operating on these children in 1998, down to 11 centres or managed clinical networks in 2011. While the rationale for centralisation was to improve the standard of care (and in so doing the outcome) for children born with cleft lip and/or palate, research was central to this process. We illustrate how research informed and shaped this service rationalisation and how it facilitated the emergence of a research culture within the newly configured teams. We also describe how these changes in service provision were linked to the development of a national research strategy and to the identification of the resources necessary to support this strategy. PMID- 22677866 TI - Earl Howe: 'We've got to have a system in which everyone has confidence.' Interview by Ruth Doherty. AB - BDJ Managing Editor, Ruth Doherty, caught up with Earl Howe at the British Dental Conference and Exhibition held in Manchester in April this year. PMID- 22677874 TI - Post-implant neuropathy of the trigeminal nerve. A case series. AB - BACKGROUND: The incidence of implant-related inferior alveolar nerve injuries (IANI) is steadily increasing within the UK population. AIMS: This study prospectively reviewed thirty cases (35% male; 65% female) of implant-related IANI seen in a specialist nerve injury clinic.Methods Neurosensory examinations were carried out to ascertain a quantifiable rating of the perception, pain profiling and functional difficulties. Data were analysed using SPSS software. RESULTS: Patients were aware of signing consent forms for the surgery in 11 cases and 8 of those felt they were not explicitly warned about nerve injury. Over 70% of patients were referred after six months post injury. Implant surgery planning involved intra-oral films only (30%), CBCT (10%), dental pantomograph (50%) and long cone peri-apical radiographs (48%). However, no radiographic evidence pre- or postoperatively was provided by the referring practitioner in 15% of cases. Intra-operative problems included bleeding and neurological symptoms. Proximity of the implant bed or implant to the inferior alveolar canal was evident radiographically. This showed contact with roof inferior alveolar nerve canal in 44% of cases, protrusion into the canal in 20% of cases, crossing of the canal in 20% cases and distance in one case, presumed to be due to local anaesthetic injury. All patients presented with a demonstrable neuropathy, which included neuropathic pain (50%) that interfered with speaking, kissing and socialising. CONCLUSIONS: Consent, preoperative planning and appropriate referral were inadequate in provision of mandibular implants in this patient group. Recommendations have been proposed to improve practice and possible novel strategies are suggested for the prevention and improved management of these complications. PMID- 22677875 TI - What factors influence the provision of preventive care by general dental practitioners? AB - BACKGROUND: What factors influence a general dental practitioner to offer preventive care to patients? A potential answer to this question is presented based on the findings of a qualitative study recently undertaken in general dental practice in Australia. METHOD: A model of how practices come to be oriented towards preventive or restorative care is described, condensing all of the findings of the study into a single framework. Eight practices were studied and highlighted the interaction between two factors: leadership in practice and prioritisation of cultural, social and economic resources. RESULTS: In this model, dentists' leadership to reorient the prioritisation of resources towards preventive care was crucial. Ideally a whole practice changed to preventive philosophy, but change was also possible in a single dentist within a practice. Prioritisation of resources was also key and interacted with dentist leadership. Prioritisation could be seen in the reorganisation of space, routines and fee schedules. During this process, one key support factor for dentists was their external networks of trusted peers and respected practicing dentists. These peers were crucial for transferring preventive knowledge within small networks of dentists who trusted one another; their influence was reportedly more important than centrally produced guidelines or academic advice. In order to help dentists change their practices towards preventive care, the findings from our study suggest that it is important to intervene in these local networks by identifying local dental opinion leaders. During this study, the key conditions needed for practices to reorient to preventive care included the presence of a committed leader with a prevention-supportive peer network, and the reorientation of space, routines and fee schedules to support preventive practice. PMID- 22677876 TI - Documentation of functional and clinical effects of infant nutrition: setting the scene for COMMENT. AB - The Early Nutrition Academy and the Child Health Foundation, in collaboration with the Committee on Nutrition, European Society for Paediatric Gastroenterology, Hepatology and Nutrition, held a workshop in March 2011 to explore guidance on acquiring evidence on the effects of nutritional interventions in infants and young children. The four objectives were to (1) provide guidance on the quality and quantity of evidence needed to justify conclusions on functional and clinical effects of nutrition in infants and young children aged <3 years; (2) agree on a range of outcome measures relevant to nutrition trials in this age group for which agreed criteria are needed; (3) agree on an updated 'core data set' that should generally be recorded in nutrition trials in infants and young children, and (4) provide guidance on the use of surrogate markers in paediatric nutrition research. The participants discussed these objectives and agreed to set up six first working groups under the auspices of the Consensus Group on Outcome Measures Made in Paediatric Enteral Nutrition Clinical Trials (COMMENT). Five groups will aim to identify and define criteria for assessing key outcomes, i.e. growth, acute diarrhoea, atopic dermatitis and cows' milk protein allergy, infections and 'gut comfort'. The sixth group will review and update the 'core data set'. The COMMENT Steering Committee will discuss and decide upon a method for reaching consensus which will be used by all working groups and plan to meet again within 2 years and to report and publish their conclusions. PMID- 22677877 TI - Acute respiratory distress in an alpaca. AB - An alpaca was presented with a history of respiratory difficulty and death. Histology of the phrenic nerves and diaphragm revealed degenerative changes consistent with denervation atrophy, and a diagnosis of diaphragmatic paralysis was established. No gross or histological abnormalities were observed in the spinal cord or other organs. The etiology of the phrenic nerve neuropathy could not be determined. The need to examine phrenic nerves and diaphragm in camelids with respiratory distress is emphasized, as failure to examine these samples will preclude a diagnosis of diaphragmatic paralysis. PMID- 22677878 TI - Randomized controlled trial comparing the McGrath videolaryngoscope with the C MAC videolaryngoscope in intubating adult patients with potential difficult airways. AB - BACKGROUND: Difficult and failed intubations, although rarely encountered, are major causes of morbidity and mortality in the current anaesthetic practice. To reduce the incidence of difficult and failed intubations, several devices including the recently developed videolaryngoscopes are available. This randomized controlled study aims to compare the use of the McGrath videolaryngoscope with the C-MAC videolaryngoscope in adult patients with potential difficult airways. METHODS: A total of 130 patients with the Mallampati grade of >=3, requiring orotracheal intubation, were randomized to either having intubation with the McGrath videolaryngoscope or the C-MAC videolaryngoscope. The primary outcome was time to intubation. The laryngoscopic view, the number of intubation attempts, the proportion of intubation success, the ease of intubation, the haemodynamic responses to intubation, and the incidence of any complications were also recorded. RESULTS: Time to successful intubation with the C-MAC videolaryngoscope was shorter when compared with the McGrath videolaryngoscope {50 s [inter-quartile range (IQR) 38-70] vs 67 s (IQR 49-108), P<0.001}, despite the McGrath videolaryngoscope providing significantly more grade 1 laryngoscopic views. The C-MAC videolaryngoscope also resulted in significantly fewer intubation attempts and greater ease of intubation when compared with the McGrath videolaryngoscope. There were no statistically significant differences in the proportion of intubation success, the number of complications, and the changes in haemodynamic responses between the two videolaryngoscopes. CONCLUSIONS: The C-MAC videolaryngoscope allowed a quicker intubation time, fewer intubation attempts, and greater ease of intubation compared with the McGrath videolaryngoscope when used in patients with the Mallampati grade of >=3. PMID- 22677879 TI - Characterization of diatomite and its application for the retention of radiocobalt: role of environmental parameters. AB - Clay minerals have been extensively studied because of their strong sorption and complexation ability. In this work, diatomite was characterized by using acid base titration. Retention of radionuclide (60)Co(II) from aqueous solution by sorption onto diatomite was investigated by using batch technique under various environmental conditions such as pH, ionic strength, humic acid (HA), fulvic acid (FA), and temperature. The results indicated that the sorption of Co(II) onto diatomite was strongly dependent on pH. At low pH value, the sorption of Co(II) was dominated by outer-sphere surface complexation and ion exchange with Na(+)/H(+) on diatomite surfaces, whereas inner-sphere surface complexation was the main sorption mechanism at high pH value. The D-R model fitted the sorption isotherms better than the Langmuir and Freundlich models. The thermodynamic parameters (DeltaH(0), DeltaS(0) and DeltaG(0)) calculated from the temperature dependent sorption isotherms suggested that the sorption of Co(II) was an endothermic and spontaneous process. In addition, diatomite showed higher sorption capacity than that of lots of the sorbents reported in the literatures we surveyed. From the results of Co(II) removal by diatomite, the optimum reaction conditions can be obtained for the maximum removal of Co(II) from water. It is clear that the best pH values of the system to remove Co(II) from solution by using diatomite are 7-8. Considering the low cost and effective disposal of Co(II)-contaminated wastewaters, the best condition for Co(II) removal is at room temperature and solid content of 0.5 g/L. The results might be important for assessing the potential of practical application of diatomite in Co(II) and related radionuclide pollution management. PMID- 22677880 TI - Evaluation of a structured report of functional prostate magnetic resonance imaging in patients with suspicion for prostate cancer or under active surveillance. AB - BACKGROUND: Functional magnetic resonance imaging (MRI) seems to be a useful tool for prostate cancer (PCa) detection in patients with a previous negative biopsy but persistently increased prostate-specific antigen (PSA) values. Additionally, it enables correct cancer localization in patients with known PCa under active surveillance to avoid misclassification on repeat biopsies. Nevertheless, suspicious lesions on MRI findings need verification by biopsy. The aim of the present study was to establish a standardized functional prostate MRI reporting scheme. METHODS: Prostate MRI with T(2)-weighted images, T(1)-weighted images, diffusion-weighted imaging, and dynamic contrast-enhanced MRI of 56 consecutive patients were performed on a 3-T scanner. Patients with prior negative random transrectal ultrasound (TRUS)-guided biopsy and continuous suspicion for PCa as well as patients under active surveillance were included. The MRI localization report of suspicious lesions followed a standardized scheme. TRUS-guided random biopsy with addition of targeted biopsy cores was performed afterwards based on the structured report. RESULTS: Of the 56 patients, 18 had suspicious MRI findings and subsequently underwent repeat biopsy under guidance of the standardized localization scheme. PCa was documented in 72% (13/18). CONCLUSIONS: A standardized reporting scheme of suspicious findings on prostate MRI leads to higher success rates as compared to standard random TRUS-guided biopsy. PMID- 22677881 TI - A pooled analysis of sequential therapies with sorafenib and sunitinib in metastatic renal cell carcinoma. AB - OBJECTIVE: To evaluate the optimal sequence for the receptor tyrosine kinase inhibitors (rTKIs) sorafenib and sunitinib in metastatic renal cell cancer. METHODS: We performed a retrospective analysis of patients who had received sequential therapy with both rTKIs and integrated these results into a pooled analysis of available data from other publications. Differences in median progression-free survival (PFS) for first- (PFS1) and second-line treatment (PFS2), and for the combined PFS (PFS1 plus PFS2) were examined using weighted linear regression. RESULTS: In the pooled analysis encompassing 853 patients, the median combined PFS for first-line sunitinib and 2nd-line sorafenib (SuSo) was 12.1 months compared with 15.4 months for the reverse sequence (SoSu; 95% CI for difference 1.45-5.12, p = 0.0013). Regarding first-line treatment, no significant difference in PFS1 was noted regardless of which drug was initially used (0.62 months average increase on sorafenib, 95% CI for difference -1.01 to 2.26, p = 0.43). In second-line treatment, sunitinib showed a significantly longer PFS2 than sorafenib (average increase 2.66 months, 95% CI 1.02-4.3, p = 0.003). CONCLUSION: The SoSu sequence translates into a longer combined PFS compared to the SuSo sequence. Predominantly the superiority of sunitinib regarding PFS2 contributed to the longer combined PFS in sequential use. PMID- 22677882 TI - Misperceiving space following shifts of attention: determining the locus of the attentional repulsion effect. AB - The Attentional Repulsion Effect (ARE) is a spatial consequence of allocating attention to peripheral locations. Specifically, a shift in attention to the periphery produces an error in the localization of visual objects in the opposite direction of the shift. Suzuki and Cavanagh proposed three possible mechanisms to account for the neural basis of the repulsion effect; surround suppression, RF shrinking, and RF recruitment. The purpose of the present experiment was to begin to investigate the ARE mechanism by determining its locus. This was achieved by assessing both monocular and binocular vision, and then by examining AREs in a condition that assesses interocular transfer, where the cue is only presented to one eye and the target is only presented to the other eye. Importantly, this latter test allowed for a direct verification of the ARE's locus. Given that the magnitude of the repulsion effect was nearly identical in the two vision conditions, and that the effect disappeared in the interocular condition, the current findings indicate that the ARE occurs early in visual processing, prior to or in the input layers of V1 and before binocular vision dominates. PMID- 22677883 TI - Impaired bone formation with a high-protein diet in rats with adriamycin-induced nephrotic syndrome. AB - BACKGROUND/AIM: The purpose of the study was to investigate the effects of a high protein (HP) diet on bone metabolism in rats with adriamycin (ADR)-induced nephrotic syndrome. METHODS: Nephrotic syndrome was established by weekly injections of ADR (2 mg/kg, i.p.) for 6 weeks. After a final injection, we confirmed that nephrotic syndrome had developed. Then, the rats were divided into two groups for the dietary treatments, namely the HP diet (30% of calories from protein) and the low-protein (LP) diet (7% of calories from protein), and were fed an isocaloric diet for the following 5 weeks. RESULTS: Urinary protein and phosphate excretion were significantly greater in the HP diet group than in the LP diet group (p < 0.05). Serum parathyroid hormone and osteocalcin levels were significantly higher and lower, respectively, in the HP diet group (p < 0.05). Femur weight, femur mass index and femur calcium contents were significantly lower in the HP diet group than in the LP diet group (p < 0.05). Bone mineral density was significantly lower in the HP diet group than in the LP diet group (p < 0.05); however, bone mineral content did not differ between the two groups. CONCLUSION: We confirmed that an HP diet negatively affects bone mineral metabolism and bone density in ADR-induced nephrotic syndrome rats. PMID- 22677885 TI - Cough-induced sinus arrest resulting in recurrent episodes of syncope: is it really transient? PMID- 22677884 TI - Memory-dependent adjustment of vocal response latencies in a territorial songbird. AB - Vocal interactions in songbirds can be used as a model system to investigate the interplay of intrinsic singing programmes (e.g. influences from vocal memories) and external variables (e.g. social factors). When characterizing vocal interactions between territorial rivals two aspects are important: (1) the timing of songs in relation to the conspecific's singing and (2) the use of a song pattern that matches the rival's song. Responses in both domains can be used to address a territorial rival. This study is the first to investigate the relation of the timing of vocal responses to (1) the vocal memory of a responding subject and (2) the selection of the song pattern that the subject uses as a response. To this end, we conducted interactive playback experiments with adult nightingales (Luscinia megarhynchos) that had been hand-reared and tutored in the laboratory. We analysed the subjects' vocal response latencies towards broadcast playback stimuli that they either had in their own vocal repertoire (songs shared with playback) or that they had not heard before (unknown songs). Likewise, we compared vocal response latencies between responses that matched the stimulus song and those that did not. Our findings showed that the latency of singing in response to the playback was shorter for shared versus unknown song stimuli when subjects overlapped the playback stimuli with their own song. Moreover birds tended to overlap faster when vocally matching the stimulus song rather than when replying with a non-matching song type. We conclude that memory of song patterns influenced response latencies and discuss possible mechanisms. PMID- 22677886 TI - Sulfur dioxide inhalation stimulated mitochondrial biogenesis in rat brains. AB - Sulfur dioxide (SO(2)) is a common environmental pollutant. Mitochondria play essential roles in energy metabolism, generation of reactive oxygen species, and regulation of apoptosis in response to neuronal brain injury. It is of interest to observe the effect of SO(2) on mitochondrial function in brain. In the present study, male Wistar rats were housed in exposure chambers and treated with 3.5, 7 and 14mg/m(3) SO(2) for 4h/day for 30days, while control rats were exposed to filtered air in the same condition. Mitochondrial membrane potential (MMP) was assessed in cerebral mitochondria using the lipophilic cationic probe JC-1. The amount of ATP was measured by the luciferinluciferase method. Analyses of mitochondrial replication and transcription were performed by real time PCR. The protein levels were detected using Western blotting. Our results showed that cerebral mtDNA content was markedly increased in rats after SO(2) exposure. Paralleling the change in mtDNA content, MMP, ATP content, MDA level, CO1 & 4 and ATP6 & 8 expression, and cytochrome c oxidase activity were increased in rat cortex after SO(2) inhalation. Moreover, mitochondrial biogenesis was accompanied by increased expression of NRF1 and TFAM, whereas PGC-1alpha was not changed. We report for the first time increased mitochondrial biogenesis in brain of rats exposed to SO(2), which might be an adaptive response to mitochondrial depletion by oxidant damage. PMID- 22677887 TI - Dihydroartemisinin inhibits the human erythroid cell differentiation by altering the cell cycle. AB - Artemisinin derivatives such as dihydroartemisinin (DHA) induce significant depletion of early embryonic erythroblasts in animal models. We have reported previously that DHA specifically targets pro-erythroblasts and basophilic erythroblasts, when human CD34+ stem cells are differentiated toward the erythroid lineage, indicating that a window of susceptibility to artemisinins may exist also in human developmental erythropoiesis during pregnancy. To better investigate the toxicity of artemisinin derivatives, the structure-activity relationship was evaluated against the K562 leukaemia cell line, used as a model for differentiating early human erythroblasts. All artemisinins derivatives, except deoxyartemisinin, inhibited both spontaneous and induced erythroid differentiation, confirming that the peroxide bridge is responsible for the erythro-toxicity. On the contrary, cell growth was markedly reduced by DHA, artemisone and artesunate but not by artemisinin, 10-deoxoartemisinin or deoxy artemisinin. The substituent at position C-10 is responsible only for the anti proliferative effect, since 10-deoxoartemisinin did not reduce cell growth but arrested the differentiation of K562 cells. In particular, the results showed that DHA resulted the most potent and rapidly acting compound of the drug family, causing (i) the decreased expression of GpA surface receptors and the down regulation the gamma-globin gene; (ii) the alteration of S phase of cell cycle and (iii) the induction of programmed cell death of early erythroblasts in a dose dependent manner within 24h. In conclusion, these findings confirm that the active metabolite DHA is responsible for the erythro-toxicity of most of artemisinins used in therapy. Thus, as long as no further clinical data are available, current WHO recommendations of avoiding malaria treatment with artemisinins during the first trimester of pregnancy remain valid. PMID- 22677888 TI - Effects of endosulfan on hepatoma cell adhesion: Epithelial-mesenchymal transition and anoikis resistance. AB - Endosulfan is an organochlorine pesticide commonly used in agriculture yet classified by the Stockholm Convention in 2011 as a persistent organic pollutant (POP). Its potential toxicity makes its continued use a major public health concern. Despite studies in laboratory animals, the molecular mechanisms underlying the carcinogenic effects of endosulfan in human liver remain poorly understood. In this study, we investigated the phenotypical effects of endosulfan on HepG2 liver cells. First, we found that endosulfan disrupted the anoikis process. Indeed, cells exposed to endosulfan were initially sensitized to anoikis and thereafter recovered their resistance to this process. This phenomenon occurred in parallel to the induction of the epithelial to mesenchymal (EMT) process, as demonstrated by: (1) reorganization of the actin cytoskeleton together with activation of the FAK signaling pathway; (2) repression of E cadherin expression; (3) induction of Snail and Slug; (4) activation of the WNT/beta-catenin pathway; and (5) induction and reorganization of mesenchymal markers (S100a4, vimentin, fibronectin, MMP-7). Secondly, despite the acquisition of mesenchymal characteristics, HepG2 cells exposed to endosulfan failed to migrate. This incapacity to acquire a motile phenotype could be attributed to a disruption of the interaction between the ECM and the cells. Taken together, these results indicate that endosulfan profoundly alters the phenotype of liver cells by inducing cell detachment and partial EMT as well as disrupting the anoikis process. All these events account, at least in part, for the carcinogenic potential of endosulfan in liver. PMID- 22677889 TI - Effect of high-dose intravenous methyl-prednisolone treatment on intraocular pressure in multiple sclerosis patients with relapse. AB - AIM: The aim of the study was to determine the intraocular pressure (IOP) changes with high-dose intravenous methylprednisolone (HIVMP) treatment given for the treatment of acute relapses in relapsing multiple sclerosis (MS). METHODS: Forty patients with clinically definite MS admitted for a new demyelinating event were included in the study. All patients were treated with HIVMP (1 g) once daily for 5 consecutive days. IOPs of 40 patients were recorded before treatment, during the course of systemic methylprednisolone administration and at the end of each month for 3 successive months, four times a day. The average IOP of each day was statistically compared to the pretreatment value. RESULTS: The initial IOP was 13.5 +/- 2.4 mm Hg before steroid administration. The IOP values tended to rise significantly during intravenous corticosteroid administration and in the first month of follow-up (p < 0.05). However, the increase remained within normal ranges and IOP values never exceeded 20 mm Hg during the follow-ups. CONCLUSION: Our study demonstrated that MS patients treated with HIVMP have increased IOP which does not lead to conditions at risk for developing glaucoma. PMID- 22677890 TI - Topographic and biomechanical evaluation of cornea in patients with ichthyosis vulgaris. AB - PURPOSE: To compare the topographic and biomechanical properties of corneas in eyes of patients with ichthyosis vulgaris (IV) and eyes of healthy individuals. METHODS: Thirty healthy individuals (control group) and 30 patients with IV (study group) were enrolled in this prospective study. Topographic measurements, including keratometry values, irregularity, and surface asymmetry index in the right eye of each participant were obtained using Scheimpflug camera with a Placido disc topographer (Sirius). Corneal hysteresis (CH), corneal resistance factor (CRF), corneal-compensated intraocular pressure (IOPcc) and Goldman related intraocular pressure (IOPg) were measured using the Reichert Ocular Response Analyzer (ORA). Central corneal thickness (CCT) was also measured with ultrasonic pachymetry and the Sirius corneal topography system. RESULTS: Topographic parameters were not significantly different between both groups (p>0.05). Although mean CH was not significantly different between the groups, the CRF was significantly lower in patients with IV (p=0.249 and p=0.005, respectively). The CCT was significantly lower in patients with IV compared to healthy controls (p<0.001). The IOPg and IOPcc were significantly lower in the patients with ichthyosis than in healthy controls (p=0.001 and p=0.004, respectively). CONCLUSIONS: The study demonstrated that while the eyes of patients with IV had corneal topographic findings and corneal hysteresis similar to those of healthy controls, some of corneal biomechanical properties such CRF and CCT and IOP values such as IOPg and IOPcc were significantly lower in patients with IV. These results should be taken into account when planning a corneal refractive surgery and glaucoma screening for patients with IV. PMID- 22677891 TI - Hepatitis E virus infection causing isolated fetal ascites: a case report. AB - Maternal hepatitis infection, excepting hepatitis E, causing isolated fetal ascites with variable outcome has been reported previously. We present a case of maternal hepatitis E virus (HEV) infection causing isolated fetal ascites which resolved spontaneously during pregnancy and resulted in a term live-born baby with anti-HEV seropositivity. A 39-year-old primigravida woman was diagnosed with acute HEV infection at 15 weeks of gestation. Ultrasound at 19 weeks showed significant fetal ascites with abdominal calcifications. Fetal karyotype did not show any abnormality. Cord blood was positive for anti-HEV IgM and negative for other intrauterine infections. Ultrasound at 25 weeks showed partial resolution of fetal ascites with complete resolution at 30 weeks. She delivered a healthy baby at 38 completed weeks, with normal liver enzymes at birth and 1-month follow up. PMID- 22677892 TI - Quantum cascades in nano-engineered superconductors: geometrical, thermal and paramagnetic effects. AB - The effect of a parallel magnetic field on the orbital motion of electrons in high-quality superconducting nanowires resulting in a superconductor-to-normal transition which occurs through a cascade of jumps in the order parameter as a function of the magnetic field. Such cascades originate from the transverse size quantization that splits the conduction band into a series of subbands. Here, based on a numerical solution of the Bogoliubov-de Gennes equations for a hollow nanocylinder, we investigate how the quantum-size cascades depend on the confining geometry, i.e., by changing the cylinder radius R and its thickness d we cover the range from the nanowire-like to the nanofilm-like regime. The cascades are shown to become much less pronounced when increasing R/d, i.e., when the nanofilm-like regime is approached. When the temperature is non-zero they are thermally smoothed. This includes the spin-magnetic-field interaction which reduces the critical (depairing) parallel magnetic field H(c,//) but does not have any qualitative effect on the quantum cascades. From our calculations it is seen that the paramagnetic limiting field H(par) significantly exceeds H(c,//) even in extremely narrow nanocylinders, i.e., when R,d are down to a few nanometers, and H(c,//) is only about 10% larger when switching-off the spin magnetic-field interaction in this case. Both characteristic fields, H(c,//) and H(par), exhibit pronounced quantum-size oscillations. We demonstrate that the quantum cascades and the quantum-size oscillations survive in the presence of surface roughness. PMID- 22677894 TI - Distribution, historical trends and inventories of polychlorinated biphenyls in sediments from Yangtze River Estuary and adjacent East China Sea. AB - A large portion of polychlorinated biphenyls (PCBs) from e-waste released into the coastal areas may be the potential source of PCBs to the global oceans. The paper presents data of PCBs concentrations in fifty surface sediment samples and a dated sediment core in Yangtze River Delta (YRE) and adjacent East China Sea (ECS). The total PCBs levels varied from 5.08 to 19.64 ng/g dry weight, with the highest concentrations situate within the river-sea boundary zone which is so called "marginal filter". Concurrent with the operation of e-waste recycling over the last two decades, PCB fluxes started to rise again after 1980s and reached a maximum in this century. The full data set was used to estimate the burden of PCBs in YRE and adjacent ECS. A total sediment burdens were 192.8 tons, with the spatial density of 364 ng/cm(2) which accounts for 1.9% of all the PCBs in China. PMID- 22677895 TI - Cardiovascular disease mortality and cancer incidence in vegetarians: a meta analysis and systematic review. AB - BACKGROUND: Prospective cohort studies have examined mortality and overall cancer incidence among vegetarians, but the results have been inconclusive. AIMS: The objective of the present meta-analysis was to investigate cardiovascular disease mortality and cancer incidence among vegetarians and nonvegetarians. METHODS: Medline, EMBASE and Web Of Science databases were searched for cohort studies published from inception to September 2011. Studies were included if they contained the relative risk (RR) and corresponding 95% CI. Participants were from the UK, Germany, California, USA, the Netherlands and Japan. RESULTS: Seven studies with a total of 124,706 participants were included in this analysis. All cause mortality in vegetarians was 9% lower than in nonvegetarians (RR = 0.91; 95% CI, 0.66-1.16). The mortality from ischemic heart disease was significantly lower in vegetarians than in nonvegetarians (RR = 0.71; 95% CI, 0.56-0.87). We observed a 16% lower mortality from circulatory diseases (RR = 0.84; 95% CI, 0.54 1.14) and a 12% lower mortality from cerebrovascular disease (RR = 0.88; 95% CI, 0.70-1.06) in vegetarians compared with nonvegetarians. Vegetarians had a significantly lower cancer incidence than nonvegetarians (RR = 0.82; 95% CI, 0.67 0.97). CONCLUSIONS: Our results suggest that vegetarians have a significantly lower ischemic heart disease mortality (29%) and overall cancer incidence (18%) than nonvegetarians. PMID- 22677896 TI - Structural and electronic properties of bilayer and trilayer graphdiyne. AB - Stimulated by the recent experimental synthesis of a new layered carbon allotrope graphdiyne film, we provide the first systematic ab initio investigation of the structural and electronic properties of bilayer and trilayer graphdiyne and explore the possibility of tuning the energy gap via a homogeneous perpendicular electric field. Our results show that the most stable bilayer and trilayer graphdiyne both have their hexagonal carbon rings stacked in a Bernal way (AB and ABA style configuration, respectively). Bilayer graphdiyne with the most and the second most stable stacking arrangements have direct bandgaps of 0.35 eV and 0.14 eV, respectively; trilayer graphdiyne with stable stacking styles have bandgaps of 0.18-0.33 eV. The bandgaps of the semiconducting bilayer and trilayer graphdiyne generally decrease with increasing external vertical electric field, irrespective of the stacking style. Therefore, the possibility of tuning the electronic structure and optical absorption of bilayer and trilayer graphdiyne with an external electric field is suggested. PMID- 22677897 TI - Photophysical and electrochemical properties of 1,3-bis(2 pyridylimino)isoindolate platinum(II) derivatives. AB - A series of twelve platinum(II) complexes of the form (N^N^N)PtX have been synthesized and characterized where N^N^N is 1,3-bis(2-pyridylimino)isoindolate ligands (BPI) or BPI ligands whose aryl moieties are substituted with tert-butyl, nitro, alkoxy, iodo or chloro groups, and X is a chloride, fluoride, cyano, acetate, phenyl or 4-(dimethylamino)phenyl ligand. All complexes display at least one irreversible oxidation and two reversible reduction waves at potentials dependent on the position and the electron donating or withdrawing nature of both X and the substituted N^N^N ligand. Broad room temperature phosphorescence ranging in energy from 594 to 680 nm was observed from the complexes, with quantum efficiencies ranging from 0.01 to 0.05. The efficiency of emission is dictated largely by nonradiative processes since the rate constants for nonradiative deactivation [(1.1-100) * 10(5) s(-1)] show greater variation than those for radiative decay [(0.57-4.0) * 0(4) s(-1)]. Nonradiative deactivation for compounds with X = Cl follow the energy gap law, i.e. the nonradiative rate constants increase exponentially with decreasing emission energy. Deactivation of the excited state appears to be strongly influenced by a non-planar distortion of the BPI ligand. PMID- 22677898 TI - Patients' experience of psoriasis in the genital area. AB - BACKGROUND: Psoriasis in the genital area is often neglected, although it bothers a substantial number of patients. OBJECTIVE: To study both the role of the physician in the treatment of genital psoriasis and the symptom intensity of these lesions as experienced by the patients. METHODS: A detailed self administered questionnaire (containing items on the role of the physician and genital symptom intensity, range 0-10) was filled in by members of the Dutch Psoriasis Society. RESULTS: Data of 277 patients with genital psoriasis were analyzed. A total of 45.8% did not discuss the presence of genital psoriasis with their physician, 25% believed that the physician paid sufficient attention to genital lesions, and 67.8% never applied treatment for genital lesions. Mean symptom intensity ranged from 2.4 to 5.1, all scores being significantly higher for women compared to men. Severe symptoms were present in up to 43.5% of patients. Of these patients, up to 38.1% did not discuss the symptoms with their physician. CONCLUSION: The consultation rate for genital lesions is low, while numerous patients report a significant burden of disease. PMID- 22677900 TI - Leg length, sitting height and postmenopausal breast cancer risk. AB - BACKGROUND: Tallness has consistently been associated with an increased risk of breast cancer. We investigated the association further by decomposing height into leg length and sitting height. METHODS: From the prospective Danish cohort 'Diet, Cancer and Health', 23 864 postmenopausal women enrolled during 1993-1997 were followed for a diagnosis of breast cancer in the Danish Cancer Registry through 2009. RESULTS: The incidence rate ratios for breast cancer were 1.11 (95% CI=1.06 1.16) for each 5 cm increase in total height and 1.09 (95% CI=1.01-1.17) and 1.14 (95% CI=1.04-1.25) for each 5 cm increase in leg length and sitting height, respectively. There was no statistical significant difference between the associations for leg length and sitting height (P=0.47). CONCLUSION: Leg length does not seem to be more strongly associated with breast cancer among postmenopausal women than sitting height. PMID- 22677901 TI - mRNA profiling of the cancer degradome in oesophago-gastric adenocarcinoma. AB - BACKGROUND: Degradation of the extracellular matrix is fundamental to tumour development, invasion and metastasis. Several protease families have been implicated in the development of a broad range of tumour types, including oesophago-gastric (OG) adenocarcinoma. The aim of this study was to analyse the expression levels of all core members of the cancer degradome in OG adenocarcinoma and to investigate the relationship between expression levels and tumour/patient variables associated with poor prognosis. METHODS: Comprehensive expression profiling of the protease families (matrix metalloproteinases (MMPs), members of the ADAM metalloproteinase-disintegrin family (ADAMs)), their inhibitors (tissue inhibitors of metalloproteinase), and molecules involved in the c-Met signalling pathway, was performed using quantitative real-time reverse transcription polymerase chain reaction in a cohort of matched malignant and benign peri-tumoural OG tissue (n=25 patients). Data were analysed with respect to clinico-pathological variables (tumour stage and grade, age, sex and pre operative plasma C-reactive protein level). RESULTS: Gene expression of MMP1, 3, 7, 9, 10, 11, 12, 16 and 24 was upregulated by factors >4-fold in OG adenocarcinoma samples compared with matched benign tissue (P<0.01). Expression of ADAM8 and ADAM15 correlated significantly with tumour stage (P=0.048 and P=0.044), and ADAM12 expression correlated with tumour grade (P=0.011). CONCLUSION: This study represents the first comprehensive quantitative analysis of the expression of proteases and their inhibitors in human OG adenocarcinoma. These findings implicate elevated ADAM8, 12 and 15 mRNA expression as potential prognostic molecular markers. PMID- 22677902 TI - miR-21, miR-17 and miR-19a induced by phosphatase of regenerating liver-3 promote the proliferation and metastasis of colon cancer. AB - BACKGROUND: Phosphatase of regenerating liver-3 (PRL-3) is an oncogene known to promote tumour metastasis, especially in colorectal cancer (CRC). Here, we demonstrate that the miR-21, miR-17 and miR-19a expressions induced by PRL-3 are involved in the proliferation and metastasis of colon cancer. METHODS: Microarray analysis and quantitative reverse-transcription polymerase chain reactions (qRT PCR) were used to investigate the changes in miRNA expression due to the overexpression of PRL-3. Transwell chamber invasion assays, CCK-8 proliferation assays and RNA interference assays were used to explore the effects of PRL-3 on miR-21, miR-17 and miR-19a expression in colon cancer cells. Immunohistochemistry and qRT-PCR were performed in colon cancer tissues to evaluate the expression of PRL-3, signal transducer and activator of transcription 3 (STAT3), miR-21, miR-17 and miR-19a. RESULTS: Our study demonstrated that the overexpression of PRL-3 in colon cancer cells induced the expression of miR-21, miR-17 and miR-19a by activating STAT3. Subsequently, these microRNAs contributed to the increased proliferation and invasiveness of the colon cancer cells. Positive correlations between PRL-3 and these microRNAs were also observed in matched primary colon cancer tissues and metastatic lesions. CONCLUSION: miR-21, miR-17 and miR-19a induced by PRL-3 contribute to the proliferation and invasion of colon cancer. PMID- 22677903 TI - Comment on 'Contribution of pelvic and para-aortic lymphadenectomy with sentinel node biopsy in patients with IB2-IIB cervical cancer'. PMID- 22677904 TI - A systemic review of toxic death in clinical oncology trials: an Achilles' heel in safety reporting revisited. AB - BACKGROUND: Toxic death is defined as study treatment-related mortality and as such is considered as an iatrogenic death. This belongs to unnatural death where an autopsy is advised. Until now, conventional autopsy is the gold standard to discriminate between pre- and post-mortem discrepancies. METHODS: The consequences of lack of systematically performing an autopsy will be explored in the setting of oncological clinical trials. RESULTS: During more than one decade, 6428 Serious Adverse Events have been registered in the EORTC Safety database on a total of 34 734 subjects. The number of deaths were 764 (mortality rate of 2.2%) whereof 255 (rate of 0.7%) toxic deaths. In 89.8% of these toxic deaths, no autopsy has been done; in 25.1% (64 cases) an inconsistent cause of death was found based on studying of the medical narrative. The autopsy rate was only 10.2% (26 out of 255) and, in 46.2% of the performed autopsies, there was a clinical pathological discrepancy. CONCLUSION: When no autopsy is performed, there is a high risk for a wrong diagnosis in case of suspected toxic death. The high discrepancy rate, possibly due to a low autopsy rate, shows that toxic death is an Achilles' heel in iatrogenic mortality. PMID- 22677906 TI - Internet chemotherapy information is of good quality: assessment with the DISCERN tool. PMID- 22677908 TI - Dietary methyl donor depletion protects against intestinal tumorigenesis in Apc(Min/+) mice. AB - Despite recent population data, the influence of dietary folate supplementation on colon cancer risk remains controversial. This study examines the effects of folate deficiency, in combination with choline, methionine, and vitamin B12 depletion, on intestinal tumorigenesis in Apc(Min/+) mice. Methyl donor sufficient (MDS) and deficient (MDD) diets were started at five or 10 weeks of age and tumors evaluated at 16 weeks. MDD suppressed intestinal tumor formation in Apc(Min/+) mice (~80%) when started at five weeks of age. The protective effect was lost when MDD was initiated at 10 weeks of age, indicating an important time dependency on cancer suppression. Concomitant with cancer protection, MDD restricted body weight gain. Therefore, a second study was conducted in which MDS was given ad libitum or pair-fed with MDD. Although small intestinal tumors were reduced 54% in pair-fed MDS mice, MDD caused a further reduction (96%). In colon, although MDD did not affect tumor numbers, tumor size was reduced. Gene expression profiling of normal-appearing colonic mucosa after 11 weeks on MDD identified a total of 493 significantly downregulated genes relative to the MDS group. Pathway analysis placed many of these genes within general categories of inflammatory signaling and cell-cycle regulation, consistent with recently published human data obtained during folate depletion. Further studies are warranted to investigate the complex interplay of methyl donor status and cancer protection in high-risk populations. PMID- 22677907 TI - A selective inhibitor of the immunoproteasome subunit LMP2 induces apoptosis in PC-3 cells and suppresses tumour growth in nude mice. AB - BACKGROUND: Although the proteasome is a validated anticancer target, the clinical application of its inhibitors has been limited because of inherent systemic toxicity. To broaden clinical utility of proteasome inhibitors as anticancer agents, it is critical to develop strategies to selectively target proteasomes in cancer cells. The immunoproteasome is an alternative form of the constitutive proteasome that is expressed at high levels in cancer tissues, but not in most normal cells in the body. METHODS: To validate the immunoproteasome as a chemotherapeutic target, an immunoproteasome catalytic subunit LMP2 targeting inhibitor and siRNA were used. The sensitivity of PC-3 prostate cancer cells to these reagents was investigated using viability assays. Further, a xenograft model of prostate cancer was studied to test the in vivo effects of LMP2 inhibition. RESULTS: A small molecule inhibitor of the immunoproteasome subunit LMP2, UK-101, induced apoptosis of PC-3 cells and resulted in significant inhibition (~50-60%) of tumour growth in vivo. Interestingly, UK-101 did not block degradation of IkappaBalpha in PC-3 cells treated with TNF-alpha, suggesting that its mode of action may be different from that of general proteasome inhibitors, such as bortezomib, which block IkappaBalpha degradation. CONCLUSION: These results strongly suggest that the immunoproteasome has important roles in cancer cell growth and thus provide a rationale for targeting the immunoproteasome in the treatment of prostate cancer. PMID- 22677909 TI - The peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp based test for epidermal growth factor receptor mutations in bronchoscopic cytological specimens of non-small cell lung cancer. AB - OBJECTIVES: Cytological examination of samples obtained by bronchoscopy is a useful method for establishing the diagnosis of non-small cell lung cancer (NSCLC). However, the utility of a highly sensitive method for the detection of epidermal growth factor receptor (EGFR) mutation in the cytological specimens has not been fully evaluated. METHODS: We retrospectively examined the efficacy of the peptide nucleic acid-locked nucleic acid polymerase chain reaction (PNA-LNA PCR) clamp method for detecting EGFR mutations in 122 bronchoscopic cytological specimens from NSCLC patients. RESULTS: Overall, 41 specimens (33.6%) were positive for EGFR mutation. Twenty-nine (39.7%) of 73 specimens obtained by using endobronchial ultrasonography with a guide sheath, 7 (33.3%) of 21 specimens obtained under direct vision by using a conventional bronchoscope, 4 (36.4%) of 11 specimens obtained by using an ultrathin bronchoscope, and 1 (5.9%) of 17 specimens obtained by endobronchial ultrasound-guided transbronchial needle aspiration were positive for EGFR mutation. Furthermore, among 22 resected NSCLC cases, the EGFR mutation status obtained from bronchoscopic materials was consistent with the status obtained from surgical samples, with the exception of 1 case. CONCLUSION: The detection of EGFR mutation by subjecting bronchoscopic cytological specimens to a PNA-LNA PCR clamp assay proves useful. PMID- 22677910 TI - MRI for clinically suspected pediatric appendicitis: an implemented program. AB - BACKGROUND: Emergent MRI is now a viable alternative to CT for evaluating appendicitis while avoiding the detrimental effects of ionizing radiation. However, primary employment of MRI in the setting of clinically suspected pediatric appendicitis has remained significantly underutilized. OBJECTIVE: To describe our institution's development and the results of a fully implemented clinical program using MRI as the primary imaging evaluation for children with suspected appendicitis. MATERIALS AND METHODS: A four-sequence MRI protocol consisting of coronal and axial single-shot turbo spin-echo (SS-TSE) T2, coronal spectral adiabatic inversion recovery (SPAIR), and axial SS-TSE T2 with fat saturation was performed on 208 children, ages 3 to 17 years, with clinically suspected appendicitis. No intravenous or oral contrast material was administered. No sedation was administered. Data collection includes two separate areas: time parameter analysis and MRI diagnostic results. RESULTS: Diagnostic accuracy of MRI for pediatric appendicitis indicated a sensitivity of 97.6% (CI: 87.1-99.9%), specificity 97.0% (CI: 93.2-99.0%), positive predictive value 88.9% (CI: 76.0-96.3%), and negative predictive value 99.4% (CI: 96.6-99.9%). Time parameter analysis indicated clinical feasibility, with time requested to first sequence obtained mean of 78.7 +/- 52.5 min, median 65 min; first-to-last sequence time stamp mean 14.2 +/- 8.8 min, median 12 min; last sequence to report mean 57.4 +/- 35.2 min, median 46 min. Mean age was 11.2 +/- 3.6 years old. Girls represented 57% of patients. CONCLUSION: MRI is an effective and efficient method of imaging children with clinically suspected appendicitis. Using an expedited four-sequence protocol, sensitivity and specificity are comparable to CT while avoiding the detrimental effects of ionizing radiation. PMID- 22677912 TI - Grain boundary sliding in pure and segregated bicrystals: a molecular dynamics and first principles study. AB - Sliding behaviors of Sigma9(221) grain boundary bicrystals have been investigated in pure metals (Al, Ag, Au, Cu, Pt and Co) and in segregated metals (Cu segregated by Al, Ag, Au, Pt and Co) by molecular dynamics simulations and first principles calculations. The grain boundary energy, the atomic size and the electronegativity of the segregated elements were not critical for the occurrence of grain boundary sliding. On the other hand, the sliding rate increased as the minimum charge density decreased at the bond critical point. This was the case for both pure grain boundary models and segregated grain boundary models. Therefore, it seems that the sliding rate depends on atomic movement at sites with minimum charge density, irrespective of the elements involved and of the presence of segregated atoms. PMID- 22677911 TI - Evaluating patient-centered care: feasibility of electronic data collection in hospitalized older adults. AB - Evaluating patient-centered care (PCC) is crucial to its improvement. This pilot study tested the feasibility of an electronic format to assess PCC during hospitalization. Using a validated indicator of PCC embedded on a mobile device, 86 older adults evaluated its delivery by registered nurses. Patients older than 85 years rated PCC poorer than those who were younger (r = -0.22; P = .04). The electronic format was appraised as feasible; it performed well and took on average 30 minutes to complete. PMID- 22677914 TI - New trends to support independence in persons with mild dementia: a mini-review. AB - Our research was motivated by the growing aging population worldwide and the need to concentrate research efforts on a specific target group; it focuses on elderly persons with physical and cognitive deficiencies. The primary goal is to enable persons with mild dementia to maximize their physical and mental functions through assistive technologies in order to be able to continue to participate in social networks and lead independent and purposeful lives. Persons with mild dementia usually have problems in performing activities of daily living due to episodic memory decline. These can include simple activities, such as bathing, changing clothes and preparing meals. Through extended field test trials involving end users, we have demonstrated that assistive technology that provides timely prompts, alarms and reminders can enable them to preserve their abilities and improve their quality of life. Understanding the user context, especially when targeting demented individuals, and providing the required personalized assistive services is the objective of our research work. Finding the appropriate user interface to interact with the provided services is often a barrier. Thus, we have adopted the approach of a multimodal interactive system with the living environment including a TV set, iPad-like tablets, sensors/actuators, and wireless speakers connected to a reasoning engine that is able to consider the complexity of the users' profile defined by his/her cognitive abilities. In this paper we will mainly focus on the interaction level with the system as well as on the validation stages performed to meet the users' requirements. This is the result of several years' work since 2006 in the frame of two projects (IST-FP6 COGKNOW European completed project and AMUPADH ongoing project in Singapore). PMID- 22677913 TI - Effects of different amine fluoride concentrations on enamel remineralization. AB - OBJECTIVES: The aim of this study was to investigate the effects of decreasing fluoride concentrations on repeated demineralizing challenges on human enamel. MATERIALS AND METHODS: In 24 teeth, 3mm*3mm windows were prepared on the buccal and lingual sides and treated in a cycling demineralization-remineralization model. Remineralization was achieved with 100, 10 and 0.1 ppm fluoride from anime fluoride. Coronal sections were cut through the artificial lesions, and three sections per tooth were investigated using polarized light microscopy and scanning electron microscopy with quantitative element analysis. RESULTS: The morphology of the lesions was studied, and the extensions of the superficial layer and the body of the lesion were measured. Using element analysis, the Ca, P and F content were determined. The body of the lesion appeared remineralized after application of 100 ppm fluoride, while remineralization of the lesion was less successful after application of 10 and 0.1 ppm fluoride. The thickness of the superficial layer increased with decreasing fluoride concentrations, and also the extension of the body of the lesion increased. Ca and P content increased with increasing fluoride concentrations. CONCLUSIONS: The effectiveness of fluoride in enamel remineralization increased with increasing fluoride concentration. CLINICAL RELEVANCE: A consistently higher level of fluoride in saliva should be a goal in caries prevention. PMID- 22677915 TI - Visible near infrared diffuse reflectance spectroscopy (VisNIR DRS) for rapid measurement of organic matter in compost. AB - Commercial compost is the inherently variable organic product of a controlled decomposition process. In the USA, assessment of compost's physicochemical parameters presently relies on standard laboratory analyses set forth in Test Methods for the Examination of Composting and Compost (TMECC). A rapid, field portable means of assessing the organic matter (OM) content of compost products would be useful to help producers ensure optimal uniformity in their compost products. Visible near infrared diffuse reflectance spectroscopy (VisNIR DRS) is a rapid, proximal-sensing technology proven effective at quantifying organic matter levels in soils. As such, VisNIR DRS was evaluated to assess its applicability to compost. Thirty-six compost samples representing a wide variety of source materials and moisture content were collected and scanned with VisNIR DRS under moist and oven-dry conditions. Partial least squares (PLS) regression and principal component regression (PCR) were used to relate the VisNIR DRS spectra with laboratory-measured OM to build compost OM prediction models. Raw reflectance, and first- and second-derivatives of the reflectance spectra were considered. In general, PLS regression outperformed PCR and the oven-dried first derivative PLS model produced an r(2) value of 0.82 along with a residual prediction deviation value of 1.72. As such, VisNIR DRS shows promise as a suitable technique for the analysis of compost OM content for dried samples. PMID- 22677916 TI - Properties of municipal solid waste incineration ashes with respect to their separation temperature. AB - Fly ashes generated by power and heating plants are commonly used in the production of building materials in some countries, mainly as partial replacement of cement or aggregates in concrete. The ashes from municipal solid waste incinerators can be applied in a similar way. However, their chemical and mineralogical composition, granulometry and toxic constituents have to be taken into account. In this paper, four types of municipal solid waste incinerator (MSWI) ashes produced by the modern MSWI facility in Liberec, Czech Republic, were investigated. The relationship between the particular ash properties (morphology, chemical composition) and its separation temperature in the incinerator line is discussed. A coal fly ash (class F) is characterized as well, for a comparison because its utilization in building industry is more developed. The studied MSWI ashes exhibit high concentration of chlorides and sulfates which is an unfavourable feature for a potential concrete admixture. On the other hand, three of four ashes are found to be pozzolanic active and certain hydration reactions are indicated. PMID- 22677918 TI - Effect of high-intensity interval training on the profile of muscle deoxygenation heterogeneity during incremental exercise. AB - This study examines the effect of high-intensity interval training (HIT) on the spatial distribution of muscle deoxygenation during incremental exercise. Young untrained male adults (n = 11) performed an incremental bicycle exercise before and after a running HIT of 6 weeks. Muscle deoxygenation (HHb) and blood volume (Hb(tot)) were monitored continuously by near-infrared spectroscopy at eight sites in the vastus lateralis. The rise in HHb during incremental exercise was significantly higher after training, in comparison with before training (P = 0.020), whereas the rise in Hb(tot) was not affected by training. The standard deviation of HHb and the relative dispersion of HHb at the eight sites were not significantly different irrespective of the intensity of exercise between pre- and post-training. After training, the standard deviation of HHb was greater at 60, 70, and 80 % of VO2(max) than at rest. Finally, training significantly increased the standard deviation of Hb(tot) (P = 0.036). These results indicate that HIT changes the muscle deoxygenation profile during incremental exercise, suggesting an improvement in the O(2) extraction with training. HIT did not reduce the spatial heterogeneity of muscle deoxygenation and blood volume during incremental exercise. This indicates that the intra-muscular distribution of the VO(2)/O(2) delivery ratio was not improved by 6 weeks HIT. PMID- 22677919 TI - Effect of time of day and partial sleep deprivation on plasma concentrations of IL-6 during a short-term maximal performance. AB - The present study was designed to evaluate the effect of time of day and partial sleep deprivation (PSD) on short-term maximal performance and level of interleukin-6 (IL-6) in trained subjects. In a randomized order, 12 football players were asked to perform a 30-s Wingate test during which we measured the peak (PP) and mean (MP) powers. Measurements were performed at 0800 and 1800 hours, after two nocturnal regimens: (1) a reference normal sleep night (RN) and (2) 4 h of PSD caused by an early awakening. Plasma IL-6 concentrations were measured before (P1), immediately after (P2), and 60 min after the exercise (P3). PP and MP improved significantly from the morning to the afternoon after RN (P < 0.05) and from the afternoon to the morning after PSD (P < 0.05). Compared to RN, PP and MP were not affected by PSD the following morning. However, there was a significant decrease in PP and MP (P < 0.001) after the PSD at 1800 hours. In all conditions, IL-6 and resting core temperature were significantly higher (P < 0.05) in the afternoon than in the morning. In all sessions, IL-6 levels increased significantly from P1 to P2 (P < 0.01) and remained elevated in the afternoon during the recovery period after PSD (P < 0.05). However, no significant difference was observed in IL-6 between P1 and P3 during RN and PSD at 0800 hours. In conclusion, a short-term high-intensity exercise may increase the IL-6 concentrations in the morning and the afternoon. Moreover, IL-6 remained elevated during the recovery period in the afternoon after the PSD at the end of the night. PMID- 22677920 TI - Corpus callosum atrophy--a simple predictor of multiple sclerosis progression: a longitudinal 9-year study. AB - AIM: To determine whether corpus callosum atrophy predicts future clinical deterioration in multiple sclerosis. METHODS: In 39 multiple sclerosis patients the area of corpus callosum in the sagittal plane, T2 and T1 lesion volumes, brain parenchymal fraction and brain atrophy were determined at baseline and 1 year after treatment initiation. Non-parametric and multiple regression models were built to identify the most reliable predictors of disability and of its changes over 9 years. RESULTS: Corpus callosum atrophy during the first year of treatment was the best predictor of disability (r = -0.56) and of its increase at 9 years (r = 0.65). Corpus callosum atrophy of at least 2% predicted increase in disability with 93% sensitivity and 73% specificity (odds ratio = 35). CONCLUSION: Corpus callosum atrophy is a simple and accurate predictor of future disability accumulation and is feasible for routine clinical practice. PMID- 22677921 TI - Large neutral amino acids: dietary effects on brain neurochemistry and function. AB - The ingestion of large neutral amino acids (LNAA), notably tryptophan, tyrosine and the branched-chain amino acids (BCAA), modifies tryptophan and tyrosine uptake into brain and their conversion to serotonin and catecholamines, respectively. The particular effect reflects the competitive nature of the transporter for LNAA at the blood-brain barrier. For example, raising blood tryptophan or tyrosine levels raises their uptake into brain, while raising blood BCAA levels lowers tryptophan and tyrosine uptake; serotonin and catecholamine synthesis in brain parallel the tryptophan and tyrosine changes. By changing blood LNAA levels, the ingestion of particular proteins causes surprisingly large variations in brain tryptophan uptake and serotonin synthesis, with minimal effects on tyrosine uptake and catecholamine synthesis. Such variations elicit predictable effects on mood, cognition and hormone secretion (prolactin, cortisol). The ingestion of mixtures of LNAA, particularly BCAA, lowers brain tryptophan uptake and serotonin synthesis. Though argued to improve physical performance by reducing serotonin function, such effects are generally considered modest at best. However, BCAA ingestion also lowers tyrosine uptake, and dopamine synthesis in brain. Increasing dopamine function in brain improves performance, suggesting that BCAA may fail to increase performance because dopamine is reduced. Conceivably, BCAA administered with tyrosine could prevent the decline in dopamine, while still eliciting a drop in serotonin. Such an LNAA mixture might thus prove an effective enhancer of physical performance. The thoughtful development and application of dietary proteins and LNAA mixtures may thus produce treatments with predictable and useful functional effects. PMID- 22677922 TI - Protective effect of the grape seed proanthocyanidin extract in a rat model of contrast-induced nephropathy. AB - AIM: Contrast-induced nephropathy (CIN) is a common cause of hospital-acquired acute renal failure. Although it is so common, there has been no approved therapy yet. We aimed to investigate the effect of grape seed proanthocyanidin extract (GSPE) on preventing CIN. MATERIALS AND METHODS: 24 rats were divided into four groups as control group, GSPE group, contrast medium (CM) group, and CM+GSPE group. The experiment was discontinued on the ninth day. Blood samples were obtained for the measurement of renal function parameters. Renal tissues of the rats were removed for the analysis of oxidative system parameters. In addition to renal histopathology, transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) was performed to determine apoptosis. RESULTS: There was a significant increase in BUN, creatinine, malondialdehyde (MDA) levels, apoptotic index (AI) and histopathological alteration in the CM group as compared to the control group. Furthermore, BUN, creatinine, MDA, total oxidant system and oxidative stress index levels, AI as well as renal histopathological alteration were significantly decreased in the CM+GSPE group. CONCLUSION: For the first time in the literature, we showed that GSPE provided biochemical and histopathological improvement in CIN. Our findings revealed that this improvement was associated with the decrease in oxidative damage and apoptosis. PMID- 22677923 TI - Acyloxybutadiene tricarbonyl iron complexes as enzyme-triggered CO-releasing molecules (ET-CORMs): a structure-activity relationship study. AB - A series of eta(4)-acyloxycyclohexadiene-Fe(CO)(3) complexes was prepared and fully characterized by spectroscopic methods including single crystal X-ray diffraction. For this purpose a new synthetic access to differently acylated 1,3- and 1,5-dienol-Fe(CO)(3) complexes was developed. The enzymatically triggered CO release from these compounds was monitored (detection of CO through GC and/or by means of a myoglobin assay) and the anti-inflammatory effect of the compounds was assessed by a cellular assay based on the inhibition of NO-production by inducible NO synthase (iNOS). It was demonstrated that the properties (rate of esterase-triggered CO release, iNOS inhibition, cytotoxicity) of the complexes strongly depend on the substitution pattern of the pi-ligand and the nature of the acyloxy substituent. PMID- 22677924 TI - Recent progress in interfacial tissue engineering approaches for osteochondral defects. AB - This review provides a brief synopsis of the anatomy and physiology of the osteochondral interface, scaffold-based and non-scaffold based approaches for engineering both tissues independently as well as recent developments in the manufacture of gradient constructs. Novel manufacturing techniques and nanotechnology will be discussed with potential application in osteochondral interfacial tissue engineering. PMID- 22677925 TI - New reference values for vitamin D. AB - In the recent past, many studies have been published on the association between vitamin D and bone health or the risk of various chronic diseases. Thus, the D-A CH reference values [D-A-CH arises from the initial letters of the common country identification for the countries Germany (D), Austria (A) and Switzerland (CH)] for the intake of vitamin D have been revised based on a critical review by the German Nutrition Society. Both dietary intake and endogenous synthesis contribute to the body's vitamin D status. Since different factors modulate the extent of endogenous vitamin D formation, quantification is hardly possible. Therefore, the new reference values for vitamin D intake are specified for a situation in which endogenous synthesis is completely missing. Based on the findings of the critical review, serum 25-hydroxyvitamin D concentrations of 50 nmol/l or higher are considered an indicator of an optimal vitamin D status. When endogenous synthesis is missing, adequate vitamin D intake is estimated as 20 ug per day for children, adolescents and adults. Dietary vitamin D intake from habitual diet is not sufficient to achieve this value. This gap has to be covered by endogenous vitamin D synthesis and/or additional intake of vitamin D. It is clearly stated that the desired vitamin D supply can be achieved without using vitamin D supplements by frequent sun exposure. PMID- 22677926 TI - Kinematic asymmetries of the lower limbs during ergometer rowing. AB - PURPOSE: Rowing injuries, particularly of the lumbar spine, are often attributed to poor technique. Rowing technique comprises a series of coordinated movements between the back, upper limbs, and lower limbs, and abnormalities in these may lead to injury. The aim of this study was to test the hypothesis that ergometer rowing is symmetrical with respect to lower limb motion and that deviations from symmetry result from rowing experience, work rate, or stroke position. METHODS: Twenty-two rowers in three levels of ability participated in this study. A motion analysis system was used with an instrumented rowing ergometer, which incorporated load cells at the handle and seat. Kinematic measurements of the knees, hips, lumbar-pelvic joints, and pelvic twist, in addition to measures of handle force, seat force, stroke length, mediolateral seat drift, and mean external power, were made during an incremental step test. RESULTS: Elite rowers exhibited the largest handle force and mean external power (P < 0.01) and least mediolateral seat drift (P < 0.01). All groups demonstrated lower limb asymmetries, with hip asymmetries significantly greater than knee asymmetries (P < 0.01). Regression analysis indicated that both hip and knee range of motion (ROM) asymmetry was significant (P < 0.05) in predicting lumbar-pelvic flexion at the catch and maximum handle force of the stroke. However, hip ROM asymmetry showed a better relation with lumbar-pelvic flexion compared with knee ROM asymmetry, explaining a greater proportion of the variance. CONCLUSION: Bilateral asymmetries during the rowing stroke, particularly at the hips, can contribute to suboptimal kinematics of the lumbar-pelvic region. Quantification of hip ROM asymmetries may therefore be a useful tool in predicting the development of low back pain in rowers. PMID- 22677928 TI - Adjustment of muscle coordination during an all-out sprint cycling task. AB - PURPOSE: This study was designed to assess muscle coordination during a specific all-out sprint cycling task (Sprint). The aim was to estimate the EMG activity level of each muscle group by referring to the submaximal cycling condition (Sub150 W) and to test the hypothesis that a maximal activity is reached for all of the muscles during Sprint. METHODS: Fifteen well-trained cyclists were tested during submaximal and sprint cycling exercises and a series of maximal voluntary contractions (MVCs) in isometric and isokinetic modes (MVC at the three lower limb joints). Crank torque and surface EMG signals for 11 lower limb muscles were continuously measured. RESULTS: Results showed that Sprint induced a very large increase of EMG activity level for the hip flexors (multiplied by 7-9 from 150 W to Sprint) and the knee flexors and hip extensors (multiplied by 5-7), whereas plantar flexors and knee extensors demonstrated a lower increase (multiplied by 2 3). During Sprint, EMG activity level failed to reach a maximal value for hamstrings, tibialis anterior, tensor fasciae latae, and gluteus maximus (i.e., <70% to 80% of peak EMG activity during MVC, P < 0.05 to P < 0.001), and individual EMG patterns demonstrated a significant earlier onset and/or later offset for the majority of the muscles (P < 0.01 to P < 0.001). CONCLUSIONS: Results clearly suggest a change in the relative contribution of the different muscles to the power production between Sub150 W and Sprint, and provide evidence that EMG activity level is not systematically maximal for all muscles involved in the all-out sprint cycling task. The longer period of activity induced during Sprint is likely to represent an interesting coordination strategy to enhance the work generated by all of the muscle groups. PMID- 22677927 TI - Blood flow restriction enhances post-resistance exercise angiogenic gene expression. AB - PURPOSE: The objective of this study is to evaluate the effects of blood flow restriction (BFR) on muscle oxygenation during low-intensity resistance exercise as well as postexercise expression of molecules related to physiological angiogenesis. METHODS: Using a randomized cross-over design, six apparently healthy young adults (22 +/- 1 yr) performed 120 unilateral knee extensions at 40% of 1 repetition maximum with and without BFR (CNTRL). Near-infrared spectroscopy was used to measure oxygenation of the vastus lateralis during exercise. Serum and muscle expression of Post-Resistance vascular endothelial growth factor (VEGF) were determined preexercise, 4 h postexercise, and 24 h postexercise. Transcript (mRNA) expression of VEGF and other angiogenic genes was also determined. RESULTS: BFR increased muscle hemoglobin (Hb) concentrations during exercise (14.4 +/- 1.6 vs. 0.9 +/- 1.6, P = 0.002), driven largely by an increase in deoxygenated Hb (11.0 +/- 2.5 vs. 0.5 +/- 1.1, P = 0.030). BFR also increased (P < 0.05) transcript expression of VEGF, VEGF-R2, hypoxia-inducible factor 1 alpha, inducible nitric oxide synthase (NOS), and neuronal NOS. The most dramatic change in response to BFR was an increase in VEGF mRNA at 4 h postexercise (4.1 +/- 0.6 vs. 0.6 +/- 0.2-fold change, P = 0.028). Compared with control, transcript expression of endothelial NOS, serum VEGF, or muscle protein expression of VEGF was not altered in response to BFR (P > 0.05). CONCLUSION: Acute BFR increases postexercise expression of mRNA related to skeletal muscle angiogenesis, plausibly in response to changes in muscle Hb concentrations. PMID- 22677929 TI - Contact photoallergy to isothipendyl chlorhydrate. AB - Isothipendyl chlorhydrate is an azaphenothiazine, an active ingredient of an antipruriginous gel, Apaisyl gel(r) (Merck Medication Familiale, Dijon, France). Although Apaisyl gel is registered and used worldwide, we present the first case of contact photoallergy to isothipendyl chlorhydrate to our knowledge. The diagnosis suspected on the basis of a positive UVA photopatch test to chlorpromazine was confirmed by a strongly positive UVA Apaisyl gel photopatch test and our photophysical studies. This case confirms the need to keep the phenothiazines in the photopatch test standard series as a diagnostic marker of phenothiazine photoallergy. PMID- 22677930 TI - Brief report: exploring the relationship between sensory processing and repetitive behaviours in Williams Syndrome. AB - This study explored the relationship between sensory processing abnormalities and repetitive behaviours in children with Williams Syndrome (WS; n = 21). This is a novel investigation bringing together two clinical phenomena for the first time in this neuro-developmental disorder. Parents completed the Sensory Profile (Short Form; Dunn in The sensory profile manual. San Antonio: The Psychological Corporation, 1999) and the Repetitive Behaviour Questionnaire (Turner 1995). A significant correlation was evident between the total scores on each of these measures; suggesting that children with WS who exhibit increased sensory processing abnormalities also display a higher number of repetitive behaviours. Further exploratory analyses of subscales of the measures indicated potentially important relationships that suggest a role for arousal regulation in the relationship between sensory processing abnormalities and repetitive behaviours in WS. PMID- 22677931 TI - Revisiting regression in autism: Heller's dementia infantilis. Includes a translation of Uber Dementia Infantilis. AB - Theodor Heller first described a severe regression of adaptive function in normally developing children, something he termed dementia infantilis, over one 100 years ago. Dementia infantilis is most closely related to the modern diagnosis, childhood disintegrative disorder. We translate Heller's paper, Uber Dementia Infantilis, and discuss similarities in presentation between Heller's cases, and a group of children with childhood disintegrative disorder. In particular we discuss a prodromal period of affective dysregulation described by Heller, and also evident in our sample, but not previously described in any detail since the publication of Uber Dementia Infantilis. PMID- 22677932 TI - Brief report: an exploratory study comparing diagnostic outcomes for autism spectrum disorders under DSM-IV-TR with the proposed DSM-5 revision. AB - The proposed revision for Autism spectrum disorders (ASDs) in the Diagnostic and Statistical Manual of Mental Disorders--Fifth Edition (DSM-5) represents a shift from the Diagnostic and Statistical Manual of Mental Disorders--Fourth Edition, Text Revision (DSM-IV-TR). As the proposed DSM-5 criteria require a higher minimum number of symptoms to be present compared to DSM-IV-TR, there have been some concerns about the impact that this will have on diagnostic outcomes. Therefore, the current study aimed to compare diagnostic outcomes using both DSM IV-TR and DSM-5 criteria for 132 children. Of the 111 participants who received an ASD diagnosis under DSM-IV-TR, 26 did not meet DSM-5 criteria. The majority of these had received a DSM-IV-TR PDD-NOS diagnosis. Implications of the results and the proposed DSM-5 changes to the ASD criteria are discussed. PMID- 22677934 TI - Five cases of contact dermatitis to a trendy pet. AB - Skin contact with animal hair may induce contact urticaria (syndrome) or protein contact dermatitis. We report here 5 cases of dermatitis due to contact with ferrets kept as pets. The nature of the skin lesions, i.e. eczematous dermatitis, as well as the history of our 5 cases point to protein contact dermatitis. Further studies are requested to confirm this hypothesis and to identify the mechanisms and allergens. Physicians must be aware of the possibility of contact dermatitis with ferrets, especially when the patient has no previous history of atopic dermatitis and presents dermatitis of the neck, arm and around mouth. PMID- 22677933 TI - Localized gastric cancer treated with chemoradation without surgery: UTMD Anderson Cancer Center experience. AB - BACKGROUND: In patients with localized gastric cancer (LGC) who are unfit for surgery, decline surgery, or have unresectable cancer, chemoradiotherapy may provide palliation; however, data in the literature are sparse. METHODS: We identified 66 LGC patients who had definitive chemoradiation but no surgery. All patients had baseline and postchemoradiation staging including an endoscopic biopsy. Multiple statistical methods were used to analyze outcomes. RESULTS: Most patients were men and most had stage III or IV cancer. Five patients were surgery eligible but declined to have surgery. The median follow-up time was 33.9 months (95% CI 18.3-49.6). The median survival time (MST) for 66 patients was only 14.5 months (95% CI 10.8-19.7) and the median relapse-free survival (RFS) was 5.03 months (95% CI 4.67-6.40). The estimated overall survival (OS) and RFS rates at 3 years were 22.6% (95% CI 13.7-37.3) and 7.7% (95% CI 3.2-18.6), respectively. Twenty-three (35%) patients who achieved a clinical complete response (cCR; negative postchemoradiation biopsy and no progression by imaging) fared better than those who achieved less than cCR (